Biomarkers of Exposure to Toxic Substances: Volume 4: Metabonomics Biomarkers to Liver and Organ Damage

DTIC Science & Technology

2009-05-01

examined the urinary metabolite profiles from rats following a single exposure to the kidney toxicants D- serine, puromycin, hippuric acid and...15. SUBJECT TERMS Amphotericin B, bioinformatics, cell cycle regulation, clinical, clustering analysis, D-serine, glomerular injury, hippuric acid ...puromycin, hippuric acid and amphotericin B at various doses, and as a function of time post-dose. In toxicology, such dose-time metabonomics studies are

Real time chemical exposure and risk monitor

DOEpatents

Thrall, Karla D.; Kenny, Donald V.; Endres, George W. R.; Sisk, Daniel R.

1997-01-01

The apparatus of the present invention is a combination of a breath interface and an external exposure dosimeter interface to a chemical analysis device, all controlled by an electronic processor for quantitatively analyzing chemical analysis data from both the breath interface and the external exposure dosimeter for determining internal tissue dose. The method of the present invention is a combination of steps of measuring an external dose, measuring breath content, then analyzing the external dose and breath content and determining internal tissue dose.

Real time chemical exposure and risk monitor

DOEpatents

Thrall, K.D.; Kenny, D.V.; Endres, G.W.R.; Sisk, D.R.

1997-07-08

The apparatus of the present invention is a combination of a breath interface and an external exposure dosimeter interface to a chemical analysis device, all controlled by an electronic processor for quantitatively analyzing chemical analysis data from both the breath interface and the external exposure dosimeter for determining internal tissue dose. The method of the present invention is a combination of steps of measuring an external dose, measuring breath content, then analyzing the external dose and breath content and determining internal tissue dose. 7 figs.

Radiation dose effect of DNA repair-related gene expression in mouse white blood cells.

PubMed

Li, Ming-juan; Wang, Wei-wei; Chen, Shi-wei; Shen, Qian; Min, Rui

2011-10-01

The aim of this study was to screen molecular biomarkers for biodosimetry from DNA repair-related gene expression profiles. Mice were subjected to whole-body exposure with 60Co gamma rays with a dose range of 0-8 Gy at a dose rate of 0.80 Gy/min. RNA was extracted from the peripheral blood of irradiated mice at 4, 8, 12, 24 and 48hrs post-irradiation. The mRNA transcriptional changes of 11 genes related to DNA damage and repair were detected using real-time quantitative polymerase chain reaction (RT-PCR). Of the 11 genes examined, CDKN1A (cyclin-dependent kinase inhibitor 1A or p21, Cip1) and ATM (ataxia telangiectasia mutated) expression levels were found to be heavily up- and down-regulated, respectively, with exposure dose increasing at different post-irradiation times. RAD50 (RAD50 homolog), PLK3 (polo-like kinase 3), GADD45A (growth arrest and DNA damage-inducible, alpha), DDB2 (damage-specific DNA-binding protein 2), BBC3 (BCL2-binding component 3) and IER5 (immediate early response 5) gene expression levels were found to undergo significant oscillating changes over a broad dose range of 2-8 Gy at post-exposure time points observed. Three of the genes were found not to change within the observed exposure dose and post-radiation time ranges. The results of this study add to the biodosimetry with biomarker data pool and will be helpful for constructing appropriate gene expression biomarker systems to evaluate radiation exposure doses.

[Absorbed dose and the effective dose of panoramic temporo mandibular joint radiography].

PubMed

Matsuo, Ayae; Okano, Tsuneichi; Gotoh, Kenichi; Yokoi, Midori; Hirukawa, Akiko; Okumura, Shinji; Koyama, Syuji

2011-01-01

This study measured the radiation doses absorbed by the patient during Panoramic temporo mandibular joint radiography (Panoramic TMJ), Schüllers method and Orbitoramus projection. The dose of the frontal view in Panoramic TMJ was compared to that with Orbitoramus projection and the lateral view in Panoramic TMJ was compared to that with Schüllers method. We measured the doses received by various organs and calculated the effective doses using the guidelines of the International Commission on Radiological Protection in Publication 103. Organ absorbed doses were measured using an anthropomorphic phantom, loaded with thermoluminescent dosimeters (TLD), located at 160 sensitive sites. The dose shows the sum value of irradiation on both the right and left sides. In addition, we set a few different exposure field sizes. The effective dose for a frontal view in Panoramic TMJ was 11 µSv, and that for the lateral view was 14 µSv. The lens of the Orbitoramus projection was 40 times higher than the frontal view in Panoramic TMJ. Although the effective dose of the lateral view in Panoramic TMJ was 3 times higher than that of the small exposure field (10×10 cm on film) in Schüller's method, it was the same as that of a mid-sized exposure field. When the exposure field in the inferior 1/3 was reduced during panoramic TMJ, the effective doses could be decreased. Therefore we recommend that the size of the exposure field in Panoramic TMJ be decreased.

Neonatal Neurobehavioral and Neuroanatomic Correlates of Prenatal Cocaine Exposure

PubMed Central

FRANK, DEBORAH A.; AUGUSTYN, MARILYN; ZUCKERMAN, BARRY S.

2008-01-01

Complex methodologic challenges face researchers studying the effects of prenatal cocaine exposure on infant outcome. These include unavoidable imprecision in ascertaining the gestational timing and dose of cocaine to which the fetus was exposed and difficulties in identifying and quantifying the confounding, mediating, and moderating variables. Review of research on neonatal behavioral and cranial ultrasound findings following in utero cocaine exposure is used to illustrate these issues. We conclude that there are measurable but not dramatic dose-related effects of prenatal cocaine exposure on infant central nervous system structure and function. The effects of dose of prenatal cocaine exposure on later child development remain to be determined. Such research would be facilitated by a scientific consensus delineating relative doses of prenatal cocaine exposure. PMID:9668396

First-principles X-ray absorption dose calculation for time-dependent mass and optical density.

PubMed

Berejnov, Viatcheslav; Rubinstein, Boris; Melo, Lis G A; Hitchcock, Adam P

2018-05-01

A dose integral of time-dependent X-ray absorption under conditions of variable photon energy and changing sample mass is derived from first principles starting with the Beer-Lambert (BL) absorption model. For a given photon energy the BL dose integral D(e, t) reduces to the product of an effective time integral T(t) and a dose rate R(e). Two approximations of the time-dependent optical density, i.e. exponential A(t) = c + aexp(-bt) for first-order kinetics and hyperbolic A(t) = c + a/(b + t) for second-order kinetics, were considered for BL dose evaluation. For both models three methods of evaluating the effective time integral are considered: analytical integration, approximation by a function, and calculation of the asymptotic behaviour at large times. Data for poly(methyl methacrylate) and perfluorosulfonic acid polymers measured by scanning transmission soft X-ray microscopy were used to test the BL dose calculation. It was found that a previous method to calculate time-dependent dose underestimates the dose in mass loss situations, depending on the applied exposure time. All these methods here show that the BL dose is proportional to the exposure time D(e, t) ≃ K(e)t.

EXPOSURE DOMAINS: ROLE OF TIMING, PATTERN AND MAGNITUDE OF EXPOSURE ON HEALTH RISKS

EPA Science Inventory

Environmental health risk assessment may be broadly separated into assessment of risks from exposures to agents affecting health endpoints for which it may be presumed there is no dose threshold, and to agents affecting endpoints that more likely have a dose threshold. For hea...

Prospective Measurement of Patient Exposure to Radiation During Pediatric Ureteroscopy

PubMed Central

Kokorowski, Paul J.; Chow, Jeanne S.; Strauss, Keith; Pennison, Melanie; Routh, Jonathan C.; Nelson, Caleb P.

2013-01-01

Objective Little data have been reported regarding radiation exposure during pediatric endourologic procedures, including ureteroscopy (URS). We sought to measure radiation exposure during pediatric URS and identify opportunities for exposure reduction. Methods We prospectively observed URS procedures as part of a quality improvement initiative. Pre-operative patient characteristics, operative factors, fluoroscopy settings and radiation exposure were recorded. Our outcomes were entrance skin dose (ESD, in mGy) and midline dose (MLD, in mGy). Specific modifiable factors were identified as targets for potential quality improvement. Results Direct observation was performed on 56 consecutive URS procedures. Mean patient age was 14.8 ± 3.8 years (range 7.4 to 19.2); 9 children were under age 12 years. Mean ESD was 46.4 ± 48 mGy. Mean MLD was 6.2 ± 5.0 mGy. The most important major determinant of radiation dose was total fluoroscopy time (mean 2.68 ± 1.8 min) followed by dose rate setting, child anterior-posterior (AP) diameter, and source to skin distance (all p<0.01). The analysis of factors affecting exposure levels found that the use of ureteral access sheaths (p=0.01) and retrograde pyelography (p=0.04) were significantly associated with fluoroscopy time. We also found that dose rate settings were higher than recommended in up to 43% of cases and ideal C-arm positioning could have reduced exposure 14% (up to 49% in some cases). Conclusions Children receive biologically significant radiation doses during URS procedures. Several modifiable factors contribute to dose and could be targeted in efforts to implement dose reduction strategies. PMID:22341275

Space: The Final Frontier-Research Relevant to Mars.

PubMed

Boice, John D

2017-04-01

A critically important gap in knowledge surrounds the health consequences of exposure to radiation received gradually over time. Much is known about the health effects of brief high-dose exposures, such as from the atomic bombings in Japan, but the concerns today focus on the frequent low-dose exposures received by members of the public, workers, and, as addressed in this paper, astronauts. Additional guidance is needed by the National Aeronautics and Space Administration (NASA) for planning long-term missions where the rate of radiation exposure is gradual over years and the cumulative amounts high. The direct study of low doses and low-dose rates is of immeasurable value in understanding the possible range of health effects from gradual exposures and in providing guidance for radiation protection, not only of workers and the public but also astronauts. The ongoing Million Person Study (MPS) is 10 times larger than the study of the Japanese atomic bomb survivors of 86,000 survivors with estimated doses. The number of workers with >100 mSv career dose is substantially greater. The large study size, broad range of doses, and long follow-up indicate substantial statistical ability to quantify the risk of exposures that are received gradually over time. The study consists of 360,000 U.S. Department of Energy workers from the Manhattan Project; 150,000 nuclear utility workers from the inception of the nuclear age; 115,000 atomic veterans who participated in above-ground atmospheric tests at the Nevada Test Site and the Bikini and Enewetak Atolls and Johnston Island in the Pacific Proving Grounds (PPG); 250,000 radiologists and medical workers; and 130,000 industrial radiographers. NASA uses an individual risk-based system for radiation protection in contrast to the system of dose limits for occupational exposures used by terrestrial-based organizations. The permissible career exposure limit set by NASA for each astronaut is a 3% risk of exposure-induced death (REID) from cancer at a 95% confidence level to account for uncertainties in risk projections. The large size of the MPS will reduce the uncertainty in the risk estimates, narrowing the 95% confidence interval, and thus allow more time in space for astronauts. Further differences between men and women in their response to radiation can be more fully examined, and non-cancer outcomes, such as neurological disorders and cardiovascular disease, can be evaluated in a way not hitherto possible.

Intussusception reduction: Effect of air vs. liquid enema on radiation dose.

PubMed

Kaplan, Summer L; Magill, Dennise; Felice, Marc A; Edgar, J Christopher; Anupindi, Sudha A; Zhu, Xiaowei

2017-10-01

Both air and radiopaque liquid contrast are used to reduce ileocolic intussusception under fluoroscopy. Some suggest air lowers radiation dose due to shorter procedure times. However, air enema likely lowers radiation dose regardless of fluoroscopy time due to less density over the automatic exposure control cells. We test the hypothesis that air enema reduction of ileocolic intussusception results in lower radiation dose than liquid contrast enema independent of fluoroscopy time. We describe a role for automatic exposure control in this dose difference. We retrospectively evaluated air and liquid intussusception reductions performed on a single digital fluoroscopic unit during a 26-month period. We compared patient age, weight, gender, exam time of day and year, performing radiologist(s), radiographic image acquisitions, grid and magnification use, fluoroscopy time and dose area product. We compared categorical and continuous variables statistically using chi-square and Mann-Whitney U tests, respectively. The mean dose area product was 2.7-fold lower for air enema, 1.3 ± 0.9 dGy·cm 2 , than for liquid, 3.5 ± 2.5 dGy·cm 2 (P<0.005). The mean fluoroscopy time was similar between techniques. The mean dose area product/min was 2.3-fold lower for air, 0.6 ± 0.2 dGy·cm 2 /min, than for liquid, 1.4 ± 0.5 dGy·cm 2 /min (P<0.001). No group differences were identified in other measured dose parameters. Fluoroscopic intussusception reduction using air enema uses less than half the radiation dose of liquid contrast enema. Dose savings are independent of fluoroscopy time and are likely due to automatic exposure control interaction.

FDA-sunlamp recommended Maximum Timer Interval And Exposure Schedule: consensus ISO/CIE dose equivalence.

PubMed

Dowdy, John C; Czako, Eugene A; Stepp, Michael E; Schlitt, Steven C; Bender, Gregory R; Khan, Lateef U; Shinneman, Kenneth D; Karos, Manuel G; Shepherd, James G; Sayre, Robert M

2011-09-01

The authors compared calculations of sunlamp maximum exposure times following current USFDA Guidance Policy on the Maximum Timer Interval and Exposure Schedule, with USFDA/CDRH proposals revising these to equivalent erythemal exposures of ISO/CIE Standard Erythema Dose (SED). In 2003, [USFDA/CDRH proposed replacing their unique CDRH/Lytle] erythema action spectrum with the ISO/CIE erythema action spectrum and revising the sunlamp maximum exposure timer to 600 J m(-2) ISO/CIE effective dose, presented as being biologically equivalent. Preliminary analysis failed to confirm said equivalence, indicating instead ∼38% increased exposure when applying these proposed revisions. To confirm and refine this finding, a collaboration of tanning bed and UV lamp manufacturers compiled 89 UV spectra representing a broad sampling of U.S. indoor tanning equipment. USFDA maximum recommended exposure time (Te) per current sunlamp guidance and CIE erythemal effectiveness per ISO/CIE standard were calculated. The CIE effective dose delivered per Te averaged 456 J(CIE) m(-2) (SD = 0.17) or ∼4.5 SED. The authors found that CDRH's proposed 600 J(CIE) m(-2) recommended maximum sunlamp exposure exceeds current Te erythemal dose by ∼33%. The current USFDA 0.75 MED initial exposure was ∼0.9 SED, consistent with 1.0 SED initial dose in existing international sunlamp standards. As no sunlamps analyzed exceeded 5 SED, a revised maximum exposure of 500 J(CIE) m(-2) (∼80% of CDRH's proposal) should be compatible with existing tanning equipment. A tanning acclimatization schedule is proposed beginning at 1 SED thrice-weekly, increasing uniformly stepwise over 4 wk to a 5 SED maximum exposure in conjunction with a tan maintenance schedule of twice-weekly 5 SED sessions, as biologically equivalent to current USFDA sunlamp policy.

Radiation exposure in transcatheter patent ductus arteriosus closure: time to tune?

PubMed

Villemain, Olivier; Malekzadeh-Milani, Sophie; Sitefane, Fidelio; Mostefa-Kara, Meriem; Boudjemline, Younes

2018-05-01

The aims of this study were to describe radiation level at our institution during transcatheter patent ductus arteriosus occlusion and to evaluate the components contributing to radiation exposure. Transcatheter occlusion relying on X-ray imaging has become the treatment of choice for patients with patent ductus arteriosus. Interventionists now work hard to minimise radiation exposure in order to reduce risk of induced cancers. We retrospectively reviewed all consecutive children who underwent transcatheter closure of patent ductus arteriosus from January 2012 to January 2016. Clinical data, anatomical characteristics, and catheterisation procedure parameters were reported. Radiation doses were analysed for the following variables: total air kerma, mGy; dose area product, Gy.cm2; dose area product per body weight, Gy.cm2/kg; and total fluoroscopic time. A total of 324 patients were included (median age=1.51 [Q1-Q3: 0.62-4.23] years; weight=10.3 [6.7-17.0] kg). In all, 322/324 (99.4%) procedures were successful. The median radiation doses were as follows: total air kerma: 26 (14.5-49.3) mGy; dose area product: 1.01 (0.56-2.24) Gy.cm2; dose area product/kg: 0.106 (0.061-0.185) Gy.cm2/kg; and fluoroscopic time: 2.8 (2-4) min. In multivariate analysis, a weight >10 kg, a ductus arteriosus width <2 mm, complications during the procedure, and a high frame rate (15 frames/second) were risk factors for an increased exposure. Lower doses of radiation can be achieved with subsequent recommendations: technical improvement, frame rate reduction, avoidance of biplane cineangiograms, use of stored fluoroscopy as much as possible, and limitation of fluoroscopic time. A greater use of echocardiography might even lessen the exposure.

The Effect of Route, Vehicle, and Divided Doses on the Pharmacokinetics of Chlorpyrifos and its Metabolite Trichloropyridinol in Neonatal Sprague-Dawley Rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marty, M. S.; Domoradzki, J. Y.; Hansen, S. C.

2007-12-01

There is a paucity of data on neonatal systemic exposure using different dosing paradigms. Male CD (Sprague-Dawley derived) rats at postnatal day (PND) 5 were dosed with chlorpyrifos (CPF, 1 mg/kg) using different routes of exposure, vehicles, and single vs. divided doses. Blood concentrations of CPF and its primary metabolite, trichloropyridinol (TCP), were measured at multiple times through 24 h. Groups included: single gavage bolus vs. divided gavage doses in corn oil (1 vs 3 times in 24 h), single gavage bolus vs. divided gavage doses in rat milk, and subcutaneous administration in DMSO. These data were compared with lactationalmore » exposure of PND 5 pups from dams exposed to CPF in the diet at 5 mg/kg/day for four weeks or published data from dams exposed to daily gavage with CPF at 5 mg/kg/day. Maternal blood CPF levels were an order of magnitude lower from dietary exposure than gavage (1.1 vs 14.8 ng/g), and blood CPF levels in PND 5 pups that nursed dietary-exposed or gavage-exposed dams were below the limit of detection. Single gavage doses of 1 mg/kg CPF in corn oil vehicle in pups resulted in CPF blood levels of 49 ng/g, and in milk vehicle about 9 ng/g. Divided doses led to lower peak CPF levels. A bolus dose of 1 mg/kg CPF in DMSO administered sc appeared to have substantially altered pharmacokinetics from orally administered chlorpyrifos. To be meaningful for risk assessment, neonatal studies require attention to the exposure scenario, since route, vehicle, dose and frequency of administration result in different systemic exposure to the test chemical and its metabolites.« less

Effect of processing time delay on the dose response of Kodak EDR2 film.

PubMed

Childress, Nathan L; Rosen, Isaac I

2004-08-01

Kodak EDR2 film is a widely used two-dimensional dosimeter for intensity modulated radiotherapy (IMRT) measurements. Our clinical use of EDR2 film for IMRT verifications revealed variations and uncertainties in dose response that were larger than expected, given that we perform film calibrations for every experimental measurement. We found that the length of time between film exposure and processing can affect the absolute dose response of EDR2 film by as much as 4%-6%. EDR2 films were exposed to 300 cGy using 6 and 18 MV 10 x 10 cm2 fields and then processed after time delays ranging from 2 min to 24 h. An ion chamber measured the relative dose for these film exposures. The ratio of optical density (OD) to dose stabilized after 3 h. Compared to its stable value, the film response was 4%-6% lower at 2 min and 1% lower at 1 h. The results of the 4 min and 1 h processing time delays were verified with a total of four different EDR2 film batches. The OD/dose response for XV2 films was consistent for time periods of 4 min and 1 h between exposure and processing. To investigate possible interactions of the processing time delay effect with dose, single EDR2 films were irradiated to eight different dose levels between 45 and 330 cGy using smaller 3 x 3 cm2 areas. These films were processed after time delays of 1, 3, and 6 h, using 6 and 18 MV photon qualities. The results at all dose levels were consistent, indicating that there is no change in the processing time delay effect for different doses. The difference in the time delay effect between the 6 and 18 MV measurements was negligible for all experiments. To rule out bias in selecting film regions for OD measurement, we compared the use of a specialized algorithm that systematically determines regions of interest inside the 10 x 10 cm2 exposure areas to manually selected regions of interest. There was a maximum difference of only 0.07% between the manually and automatically selected regions, indicating that the use of a systematic algorithm to determine regions of interest in large and fairly uniform areas is not necessary. Based on these results, we recommend a minimum time of 1 h between exposure and processing for all EDR2 film measurements.

Vocal Dose Measures: Quantifying Accumulated Vibration Exposure in Vocal Fold Tissues

PubMed Central

Titze, Ingo R.; Švec, Jan G.; Popolo, Peter S.

2011-01-01

To measure the exposure to self-induced tissue vibration in speech, three vocal doses were defined and described: distance dose, which accumulates the distance that tissue particles of the vocal folds travel in an oscillatory trajectory; energy dissipation dose, which accumulates the total amount of heat dissipated over a unit volume of vocal fold tissues; and time dose, which accumulates the total phonation time. These doses were compared to a previously used vocal dose measure, the vocal loading index, which accumulates the number of vibration cycles of the vocal folds. Empirical rules for viscosity and vocal fold deformation were used to calculate all the doses from the fundamental frequency (F0) and sound pressure level (SPL) values of speech. Six participants were asked to read in normal, monotone, and exaggerated speech and the doses associated with these vocalizations were calculated. The results showed that large F0 and SPL variations in speech affected the dose measures, suggesting that accumulation of phonation time alone is insufficient. The vibration exposure of the vocal folds in normal speech was related to the industrial limits for hand-transmitted vibration, in which the safe distance dose was derived to be about 500 m. This limit was found rather low for vocalization; it was related to a comparable time dose of about 17 min of continuous vocalization, or about 35 min of continuous reading with normal breathing and unvoiced segments. The voicing pauses in normal speech and dialogue effectively prolong the safe time dose. The derived safety limits for vocalization will likely require refinement based on a more detailed knowledge of the differences in hand and vocal fold tissue morphology and their response to vibrational stress, and on the effect of recovery of the vocal fold tissue during voicing pauses. PMID:12959470

Vocal dose measures: quantifying accumulated vibration exposure in vocal fold tissues.

PubMed

Titze, Ingo R; Svec, Jan G; Popolo, Peter S

2003-08-01

To measure the exposure to self-induced tissue vibration in speech, three vocal doses were defined and described: distance dose, which accumulates the distance that tissue particles of the vocal folds travel in an oscillatory trajectory; energy dissipation dose, which accumulates the total amount of heat dissipated over a unit volume of vocal fold tissues; and time dose, which accumulates the total phonation time. These doses were compared to a previously used vocal dose measure, the vocal loading index, which accumulates the number of vibration cycles of the vocal folds. Empirical rules for viscosity and vocal fold deformation were used to calculate all the doses from the fundamental frequency (F0) and sound pressure level (SPL) values of speech. Six participants were asked to read in normal, monotone, and exaggerated speech and the doses associated with these vocalizations were calculated. The results showed that large F0 and SPL variations in speech affected the dose measures, suggesting that accumulation of phonation time alone is insufficient. The vibration exposure of the vocal folds in normal speech was related to the industrial limits for hand-transmitted vibration, in which the safe distance dose was derived to be about 500 m. This limit was found rather low for vocalization; it was related to a comparable time dose of about 17 min of continuous vocalization, or about 35 min of continuous reading with normal breathing and unvoiced segments. The voicing pauses in normal speech and dialogue effectively prolong the safe time dose. The derived safety limits for vocalization will likely require refinement based on a more detailed knowledge of the differences in hand and vocal fold tissue morphology and their response to vibrational stress, and on the effect of recovery of the vocal fold tissue during voicing pauses.

Personal exposure to ultrafine particles: the influence of time-activity patterns.

PubMed

Buonanno, G; Stabile, L; Morawska, L

2014-01-15

Exposure to ultrafine particles (UFPs) is deemed to be a major risk affecting human health. Therefore, airborne particle studies were performed in the recent years to evaluate the most critical micro-environments, as well as identifying the main UFP sources. Nonetheless, in order to properly evaluate the UFP exposure, personal monitoring is required as the only way to relate particle exposure levels to the activities performed and micro-environments visited. To this purpose, in the present work, the results of experimental analysis aimed at showing the effect of the time-activity patterns on UFP personal exposure are reported. In particular, 24 non-smoking couples (12 during winter and summer time, respectively), comprised of a man who worked full-time and a woman who was a homemaker, were analyzed using personal particle counter and GPS monitors. Each couple was investigated for a 48-h period, during which they also filled out a diary reporting the daily activities performed. Time activity patterns, particle number concentration exposure and the related dose received by the participants, in terms of particle alveolar-deposited surface area, were measured. The average exposure to particle number concentration was higher for women during both summer and winter (Summer: women 1.8 × 10(4) part. cm(-3); men 9.2 × 10(3) part. cm(-3); Winter: women 2.9 × 10(4) part. cm(-3); men 1.3 × 10(4) part. cm(-3)), which was likely due to the time spent undertaking cooking activities. Staying indoors after cooking also led to higher alveolar-deposited surface area dose for both women and men during the winter time (9.12 × 10(2) and 6.33 × 10(2) mm(2), respectively), when indoor ventilation was greatly reduced. The effect of cooking activities was also detected in terms of women's dose intensity (dose per unit time), being 8.6 and 6.6 in winter and summer, respectively. On the contrary, the highest dose intensity activity for men was time spent using transportation (2.8 in both winter and summer). © 2013.

The value of thyroid shielding in intraoral radiography

PubMed Central

Hazenoot, Bart; Sanderink, Gerard C H; Berkhout, W Erwin R

2016-01-01

Objectives: To evaluate the utility of the application of a thyroid shield in intraoral radiography when using rectangular collimation. Methods: Experimental data were obtained by measuring the absorbed dose at the position of the thyroid gland in a RANDO® (The Phantom Laboratory, Salem, NY) male phantom with a dosemeter. Four protocols were tested: round collimation and rectangular collimation, both with and without thyroid shield. Five exposure positions were deployed: upper incisor (Isup), upper canine (Csup), upper premolar (Psup), upper molar (Msup) and posterior bitewing (BW). Exposures were made with 70 kV and 7 mA and were repeated 10 times. The exposure times were as recommended for the exposure positions for the respective collimator type by the manufacturer for digital imaging. The data were statistically analyzed with a three-way ANOVA test. Significance was set at p < 0.01. Results: The ANOVA test revealed that the differences between mean doses of all protocols and geometries were statistically significant, p < 0.001. For the Isup, thyroid dose levels were comparable with both collimators at a level indicating primary beam exposure. Thyroid shield reduced this dose with circa 75%. For the Csup position, round collimation also revealed primary beam exposure, and thyroid shield yield was 70%. In Csup with rectangular collimation, the thyroid dose was reduced with a factor 4 compared with round collimation and thyroid shield yielded an additional 42% dose reduction. The thyroid dose levels for the Csup, Psup, Msup and BW exposures were lower with rectangular collimation without thyroid shield than with round collimation with thyroid shield. With rectangular collimation, the thyroid shield in Psup, Msup and BW reduced the dose 10% or less, where dose levels were already low, implying no clinical significance. Conclusions: For the exposures in the upper anterior region, thyroid shield results in an important dose reduction for the thyroid. For the other exposures, thyroid shield augments little to the reduction achieved by rectangular collimation. The use of thyroid shield is to be advised, when performing upper anterior radiography. PMID:27008105

Summary of retrospective asbestos and welding fume exposure estimates for a nuclear naval shipyard and their correlation with radiation exposure estimates.

PubMed

Zaebst, D D; Seel, E A; Yiin, J H; Nowlin, S J; Chen, P

2009-07-01

In support of a nested case-control study at a U.S. naval shipyard, the results of the reconstruction of historical exposures were summarized, and an analysis was undertaken to determine the impact of historical exposures to potential chemical confounders. The nested case-control study (N = 4388) primarily assessed the relationship between lung cancer and external ionizing radiation. Chemical confounders considered important were asbestos and welding fume (as iron oxide fume), and the chromium and nickel content of welding fume. Exposures to the potential confounders were estimated by an expert panel based on a set of quantitatively defined categories of exposure. Distributions of the estimated exposures and trends in exposures over time were examined for the study population. Scatter plots and Spearman rank correlation coefficients were used to assess the degree of association between the estimates of exposure to asbestos, welding fume, and ionizing radiation. Correlation coefficients were calculated separately for 0-, 15-, 20-, and 25-year time-lagged cumulative exposures, total radiation dose (which included medical X-ray dose) and occupational radiation dose. Exposed workers' estimated cumulative exposures to asbestos ranged from 0.01 fiber-days/cm(3) to just under 20,000 fiber-days/cm(3), with a median of 29.0 fiber-days/cm(3). Estimated cumulative exposures to welding fume ranged from 0.16 mg-days/m(3) to just over 30,000 mg-days/m(3), with a median of 603 mg-days/m(3). Spearman correlation coefficients between cumulative radiation dose and cumulative asbestos exposures ranged from 0.09 (occupational dose) to 0.47 (total radiation dose), and those between radiation and welding fume from 0.14 to 0.47. The estimates of relative risk for ionizing radiation and lung cancer were unchanged when lowest and highest estimates of asbestos and welding fume were considered. These results suggest a fairly large proportion of study population workers were exposed to asbestos and welding fume, that the absolute level of confounding exposure did not affect the risk estimates, and that weak relationships existed between monitored lifetime cumulative occupational radiation dose and asbestos or welding fume.

Radiation exposure of the radiologist's eye lens during CT-guided interventions.

PubMed

Heusch, Philipp; Kröpil, Patric; Buchbender, Christian; Aissa, Joel; Lanzman, Rotem S; Heusner, Till A; Ewen, Klaus; Antoch, Gerald; Fürst, Günther

2014-02-01

In the past decade the number of computed tomography (CT)-guided procedures performed by interventional radiologists have increased, leading to a significantly higher radiation exposure of the interventionalist's eye lens. Because of growing concern that there is a stochastic effect for the development of lens opacification, eye lens dose reduction for operators and patients should be of maximal interest. To determine the interventionalist's equivalent eye lens dose during CT-guided interventions and to relate the results to the maximum of the recommended equivalent dose limit. During 89 CT-guided interventions (e.g. biopsies, drainage procedures, etc.) measurements of eye lens' radiation doses were obtained from a dedicated dosimeter system for scattered radiation. The sensor of the personal dosimeter system was clipped onto the side of the lead glasses which was located nearest to the CT gantry. After the procedure, radiation dose (µSv), dose rate (µSv/min) and the total exposure time (s) were recorded. For all 89 interventions, the median total exposure lens dose was 3.3 µSv (range, 0.03-218.9 µSv) for a median exposure time of 26.2 s (range, 1.1-94.0 s). The median dose rate was 13.9 µSv/min (range, 1.1-335.5 µSv/min). Estimating 50-200 CT-guided interventions per year performed by one interventionalist, the median dose of the eye lens of the interventional radiologist does not exceed the maximum of the ICRP-recommended equivalent eye lens dose limit of 20 mSv per year.

Assessment of human exposure doses received by activation of medical linear accelerator components

NASA Astrophysics Data System (ADS)

Lee, D.-Y.; Kim, J.-H.; Park, E.-T.

2017-08-01

This study analyzes the radiation exposure dose that an operator can receive from radioactive components during maintenance or repair of a linear accelerator. This study further aims to evaluate radiological safety. Simulations are performed on 10 MV and 15 MV photon beams, which are the most frequently used high-energy beams in clinics. The simulation analyzes components in order of activity and the human exposure dose based on the amount of neutrons received. As a result, the neutron dose, radiation dose, and human exposure dose are ranked in order of target, primary collimator, flattening filter, multi-leaf collimator, and secondary collimator, where the minimum dose is 9.34E-07 mSv/h and the maximum is 1.71E-02 mSv/h. When applying the general dose limit (radiation worker 20 mSv/year, pubic 1 mSv/year) in accordance with the Nuclear Safety Act, all components of a linear accelerator are evaluated as below the threshold value. Therefore, the results suggest that there is no serious safety issue for operators in maintaining and repairing a linear accelerator. Nevertheless, if an operator recognizes an exposure from the components of a linear accelerator during operation and considers the operating time and shielding against external exposure, exposure of the operator is expected to be minimized.

Radiation safety protocol using real-time dose reporting reduces patient exposure in pediatric electrophysiology procedures.

PubMed

Patel, Akash R; Ganley, Jamie; Zhu, Xiaowei; Rome, Jonathan J; Shah, Maully; Glatz, Andrew C

2014-10-01

Radiation exposure during pediatric catheterization is significant. We sought to describe radiation exposure and the effectiveness of radiation safety protocols in reducing exposure during catheter ablations with electrophysiology studies in children and patients with congenital heart disease. We additionally sought to identify at-risk patients. We retrospectively reviewed all interventional electrophysiology procedures performed from April 2009 to September 2011 (6 months preceding intervention, 12 months following implementation of initial radiation safety protocol, and 8 months following implementation of modified protocol). The protocols consisted of low pulse rate fluoroscopy settings, operator notification of skin entrance dose every 1,000 mGy, adjusting cameras by >5 at every 1,000 mGy, and appropriate collimation. The cohort consisted of 291 patients (70 pre-intervention, 137 after initial protocol implementation, 84 after modified protocol implementation) at a median age of 14.9 years with congenital heart disease present in 11 %. Diagnoses included atrioventricular nodal reentrant tachycardia (25 %), atrioventricular reentrant tachycardia (61 %), atrial tachycardias (12 %), and ventricular tachycardia (2 %). There were no differences between groups based on patient, arrhythmia, and procedural characteristics. Following implementation of the protocols, there were significant reductions in all measures of radiation exposure: fluoroscopy time (17.8 %), dose area product (80.2 %), skin entry dose (81.0 %), and effective dose (76.9 %), p = 0.0001. Independent predictors of increased radiation exposure included larger patient weight, longer fluoroscopy time, and lack of radiation safety protocol. Implementation of a radiation safety protocol for pediatric and congenital catheter ablations can drastically reduce radiation exposure to patients without affecting procedural success.

Dose Reconstruction of Di(2-ethylhexyl) Phthalate Using a Simple Pharmacokinetic Model

PubMed Central

Calafat, Antonia M.

2012-01-01

Background: Di(2-ethylhexyl) phthalate (DEHP), used primarily as a plasticizer for polyvinyl chloride, is found in a variety of products. Previous studies have quantified human exposure by back calculating intakes based on DEHP metabolite concentrations in urine and by determining concentrations of DEHP in exposure media (e.g., air, food, dust). Objectives: To better understand the timing and extent of DEHP exposure, we used a simple pharmacokinetic model to “reconstruct” the DEHP dose responsible for the presence of DEHP metabolites in urine. Methods: We analyzed urine samples from eight adults for four DEHP metabolites [mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-carboxypentyl) phthalate]. Participants provided full volumes of all voids over 1 week and recorded the time of each void and information on diet, driving, and outdoor activities. Using a model previously calibrated on a single person self-dosed with DEHP in conjunction with the eight participants’ data, we used a simple trial-and-error method to determine times and doses of DEHP that resulted in a best fit of predicted and observed urinary concentrations of the metabolites. Results: The average daily mean and median reconstructed DEHP doses were 10.9 and 5.0 µg/kg-day, respectively. The highest single modeled dose of 60 µg/kg occurred when one study participant reported consuming coffee and a bagel with egg and sausage that was purchased at a gas station. About two-thirds of all modeled intake events occurred near the time of reported food or beverage consumption. Twenty percent of the modeled DEHP exposure occurred between 2200 hours and 0500 hours. Conclusions: Dose reconstruction using pharmacokinetic models—in conjunction with biomonitoring data, diary information, and other related data—can provide a powerful means to define timing, magnitude, and possible sources of exposure to a given contaminant. PMID:23010619

Population Pharmacokinetics of Rifapentine and Desacetyl Rifapentine in Healthy Volunteers: Nonlinearities in Clearance and Bioavailability

PubMed Central

Lu, Yanhui; Bliven-Sizemore, Erin; Weiner, Marc; Nuermberger, Eric; Burman, William; Dorman, Susan E.; Dooley, Kelly E.

2014-01-01

Rifapentine is under active investigation as a potent drug that may help shorten the tuberculosis (TB) treatment duration. A previous rifapentine dose escalation study with daily dosing indicated a possible decrease in bioavailability as the dose increased and an increase in clearance over time for rifapentine and its active metabolite, desacetyl rifapentine. This study aimed to assess the effects of increasing doses on rifapentine absorption and bioavailability and to evaluate the clearance changes over 14 days. A population analysis was performed with nonlinear mixed-effects modeling. Absorption, time-varying clearance, bioavailability, and empirical and semimechanistic autoinduction models were investigated. A one-compartment model linked to a transit compartment absorption model best described the data. The bioavailability of rifapentine decreased linearly by 2.5% for each 100-mg increase in dose. The autoinduction model suggested a dose-independent linear increase in clearance of the parent drug and metabolite over time from 1.2 and 3.1 liters · h−1, respectively, after a single dose to 2.2 and 5.0 liters · h−1, respectively, after 14 once-daily doses, with no plateau being reached by day 14. In clinical trial simulations using the final model, rifapentine demonstrated less-than-dose-proportional pharmacokinetics, but there was no plateau in exposures over the dose range tested (450 to 1,800 mg), and divided dosing increased exposures significantly. Thus, the proposed compartmental model incorporating daily dosing of rifapentine over a wide range of doses and time-related changes in bioavailability and clearance provides a useful tool for estimation of drug exposure that can be used to optimize rifapentine dosing for TB treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT01162486.) PMID:24614383

Patient doses and occupational exposure in a hybrid operating room.

PubMed

Andrés, C; Pérez-García, H; Agulla, M; Torres, R; Miguel, D; Del Castillo, A; Flota, C M; Alonso, D; de Frutos, J; Vaquero, C

2017-05-01

This study aimed to characterize the radiation exposure to patients and workers in a new vascular hybrid operating room during X-ray-guided procedures. During one year, data from 260 interventions performed in a hybrid operating room equipped with a Siemens Artis Zeego angiography system were monitored. The patient doses were analysed using the following parameters: radiation time, kerma-area product, patient entrance reference point dose and peak skin dose. Staff radiation exposure and ambient dose equivalent were also measured using direct reading dosimeters and thermoluminescent dosimeters. The radiation time, kerma-area product, patient entrance reference point dose and peak skin dose were, on average, 19:15min, 67Gy·cm 2 , 0.41Gy and 0.23Gy, respectively. Although the contribution of the acquisition mode was smaller than 5% in terms of the radiation time, this mode accounted for more than 60% of the effective dose per patient. All of the worker dose measurements remained below the limits established by law. The working conditions in the hybrid operating room HOR are safe in terms of patient and staff radiation protection. Nevertheless, doses are highly dependent on the workload; thus, further research is necessary to evaluate any possible radiological deviation of the daily working conditions in the HOR. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Analysis of dose to patient, spouse/caretaker, and staff, from an implanted trackable radioactive fiducial for use in the radiation treatment of prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neustadter, David; Barnea, Gideon; Stokar, Saul

Purpose: A fiducial tracking system based on a novel radioactive tracking technology is being developed for real-time target tracking in radiation therapy. In this study, the authors calculate the radiation dose to the patient, the spouse/caretaker, and the medical staff that would result from a 100 {mu}Ci Ir192 radioactive fiducial marker permanently implanted in the prostate of a radiation therapy patient. Methods: Local tissue dose was calculated by Monte Carlo simulation. The patient's whole body effective dose equivalent was calculated by summing the doses to the sensitive organs. Exposure of the spouse/caretaker was calculated from the NRC guidelines. Exposure ofmore » the medical staff was based on estimates of proximity to and time spent with the patient. Results: The local dose is below 40 Gy at 5 mm from the marker and below 10 Gy at 10 mm from the marker. The whole body effective dose equivalent to the patient is 64 mSv. The dose to the spouse/caretaker is 0.25 mSv. The annual exposures of the medical staff are 0.2 mSv for a doctor performing implantations and 0.34 mSv for a radiation therapist positioning patients for therapy. Conclusions: The local dose is not expected to have any clinically significant effect on the surrounding tissue which is irradiated during therapy. The dose to the patient is small in comparison to the whole body dose received from the therapy itself. The exposure of all other people is well below the recommended limits. The authors conclude that there is no radiation exposure related contraindication for use of this technology in the radiation treatment of prostate cancer.« less

Acute exposure to vibration is an apoptosis-inducing stimulus in the vocal fold epithelium.

PubMed

Novaleski, Carolyn K; Kimball, Emily E; Mizuta, Masanobu; Rousseau, Bernard

2016-10-01

Clinical voice disorders pose significant communication-related challenges to patients. The purpose of this study was to quantify the rate of apoptosis and tumor necrosis factor-alpha (TNF-α) signaling in vocal fold epithelial cells in response to increasing time-doses and cycle-doses of vibration. 20 New Zealand white breeder rabbits were randomized to three groups of time-doses of vibration exposure (30, 60, 120min) or a control group (120min of vocal fold adduction and abduction). Estimated cycle-doses of vocal fold vibration were extrapolated based on mean fundamental frequency. Laryngeal tissue specimens were evaluated for apoptosis and gene transcript and protein levels of TNF-α. Results revealed that terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was significantly higher after 120min of vibration compared to the control. Transmission electron microscopy (TEM) revealed no significant effect of time-dose on the mean area of epithelial cell nuclei. Extrapolated cycle-doses of vibration exposure were closely related to experimental time-dose conditions, although no significant correlations were observed with TUNEL staining or mean area of epithelial cell nuclei. TUNEL staining was positively correlated with TNF-α protein expression. Our findings suggest that apoptosis can be induced in the vocal fold epithelium after 120min of modal intensity phonation. In contrast, shorter durations of vibration exposure do not result in apoptosis signaling. However, morphological features of apoptosis are not observed using TEM. Future studies are necessary to examine the contribution of abnormal apoptosis to vocal fold diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute Exposure to Vibration is an Apoptosis-Inducing Stimulus in the Vocal Fold Epithelium

PubMed Central

Novaleski, Carolyn K.; Kimball, Emily E.; Mizuta, Masanobu; Rousseau, Bernard

2016-01-01

Clinical voice disorders pose significant communication-related challenges to patients. The purpose of this study was to quantify the rate of apoptosis and tumor necrosis factor-alpha (TNF-α) signaling in vocal fold epithelial cells in response to increasing time-doses and cycle-doses of vibration. 20 New Zealand white breeder rabbits were randomized to three groups of time-doses of vibration exposure (30, 60, 120 minutes) or a control group (120 minutes of vocal fold adduction and abduction). Estimated cycle-doses of vocal fold vibration were extrapolated based on mean fundamental frequency. Laryngeal tissue specimens were evaluated for apoptosis and gene transcript and protein levels of TNF-α. Results revealed that terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was significantly higher after 120 minutes of vibration compared to the control. Transmission electron microscopy (TEM) revealed no significant effect of time-dose on the mean area of epithelial cell nuclei. Extrapolated cycle-doses of vibration exposure were closely related to experimental time-dose conditions, although no significant correlations were observed with TUNEL staining or mean area of epithelial cell nuclei. TUNEL staining was positively correlated with TNF-α protein expression. Our findings suggest that apoptosis can be induced in the vocal fold epithelium after 120 minutes of modal intensity phonation. In contrast, shorter durations of vibration exposure do not result in apoptosis signaling. However, morphological features of apoptosis are not observed using TEM. Future studies are necessary to examine the contribution of abnormal apoptosis to vocal fold diseases. PMID:27577014

Current methods of monitoring radiation exposure from CT.

PubMed

Talati, Ronak K; Dunkin, Jared; Parikh, Shrujal; Moore, William H

2013-09-01

Increased public and regulatory scrutiny of imaging-related radiation exposure requires familiarity with current dose-monitoring techniques and best practices. CT-related ionizing radiation exposure has been cited as the largest and fastest growing source of population-wide iatrogenic ionizing radiation exposure. Upcoming federal regulations require imaging centers to familiarize themselves with available dose-monitoring techniques and implement comprehensive strategies to track patient dose, with particular emphasis on CT. Because of institution-specific and vendor-specific technologies, there are significant barriers to adoption and implementation. In this article, the authors outline the core components of a universal dose-monitoring strategy and detail a few of the many available commercial platforms. In addition, the authors introduce a cloud-based hybrid model dose-tracking system with the goal of rapid implementation, multicenter scalability, real-time dose feedback for technologists, cumulative dose monitoring, and optional dose communication to patients and into the record; doing so results in improved patient loyalty, referring physician satisfaction, and opportunity for repeat business. Copyright © 2013 American College of Radiology. All rights reserved.

THE STATE OF IMMUNITY IN GUINEA-PIGS IMMUNIZED WITH LIVE BRUCELLOSIS VACCINE AND EXPOSED TO RADIATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shevtsova, Z.V.

1960-01-01

On immunization with 19-BA live brucellosis vaccine on the 3rd and 10th days after exposure to radiation in a dose of 200 r, guinea pigs died 4 and 2 times more frequently than unvaccinated guinea pigs. If immunization was carried out on the 30th day after irradiation the mortality among irradiated animals showed only a slight increase compared with the mortality among unvaccinated control animals. Immunization carried out before exposure to radiation had no influence upon the mortality of the animals caused by radiation sickness. Guinea pigs immunized after exposure to radiation were insusceptible when infected with the doses ofmore » virulent strains of Brucella usually employed to challenge immunity (2-4 infective doses). If, however, the animals were infected with a dose twice as high (8 infective doses) the degree of immunity proved to be lower in guinea pigs exposed to radiation, than in guinea pigs immunized and not exposed to radiation. Exposure of guinea pigs to radiation at a time when immunity had already developed had no influence upon the degree of immunity on infection with 4 infective doses of the virulent strain. (auth)« less

Residential Exposure to Natural Background Radiation and Risk of Childhood Acute Leukemia in France, 1990-2009.

PubMed

Demoury, Claire; Marquant, Fabienne; Ielsch, Géraldine; Goujon, Stéphanie; Debayle, Christophe; Faure, Laure; Coste, Astrid; Laurent, Olivier; Guillevic, Jérôme; Laurier, Dominique; Hémon, Denis; Clavel, Jacqueline

2017-04-01

Exposures to high-dose ionizing radiation and high-dose rate ionizing radiation are established risk factors for childhood acute leukemia (AL). The risk of AL following exposure to lower doses due to natural background radiation (NBR) has yet to be conclusively determined. AL cases diagnosed over 1990-2009 (9,056 cases) were identified and their municipality of residence at diagnosis collected by the National Registry of Childhood Cancers. The Geocap study, which included the 2,763 cases in 2002-2007 and 30,000 population controls, was used for complementary analyses. NBR exposures were modeled on a fine scale (36,326 municipalities) based on measurement campaigns and geological data. The power to detect an association between AL and dose to the red bone marrow (RBM) fitting UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) predictions was 92%, 45% and 99% for exposure to natural gamma radiation, radon and total radiation, respectively. AL risk, irrespective of subtype and age group, was not associated with the exposure of municipalities to radon or gamma radiation in terms of yearly exposure at age reached, cumulative exposure or RBM dose. There was no confounding effect of census-based socio-demographic indicators, or environmental factors (road traffic, high voltage power lines, vicinity of nuclear plants) related to AL in the Geocap study. Our findings do not support the hypothesis that residential exposure to NBR increases the risk of AL, despite the large size of the study, fine scale exposure estimates and wide range of exposures over France. However, our results at the time of diagnosis do not rule out a slight association with gamma radiation at the time of birth, which would be more in line with the recent findings in the UK and Switzerland.

Shorter Exposures to Harder X-Rays Trigger Early Apoptotic Events in Xenopus laevis Embryos

PubMed Central

Dong, JiaJia; Mury, Sean P.; Drahos, Karen E.; Moscovitch, Marko

2010-01-01

Background A long-standing conventional view of radiation-induced apoptosis is that increased exposure results in augmented apoptosis in a biological system, with a threshold below which radiation doses do not cause any significant increase in cell death. The consequences of this belief impact the extent to which malignant diseases and non-malignant conditions are therapeutically treated and how radiation is used in combination with other therapies. Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems. Methodology/Principal Findings We explored how the energy of individual X-ray photons and exposure time, both factors that determine the total dose, influence the occurrence of cell death in early Xenopus embryo. Three different experimental scenarios were analyzed and morphological and biochemical hallmarks of apoptosis were evaluated. Initially, we examined cell death events in embryos exposed to increasing incident energies when the exposure time was preset. Then, we evaluated the embryo's response when the exposure time was augmented while the energy value remained constant. Lastly, we studied the incidence of apoptosis in embryos exposed to an equal total dose of radiation that resulted from increasing the incoming energy while lowering the exposure time. Conclusions/Significance Overall, our data establish that the energy of the incident photon is a major contributor to the outcome of the biological system. In particular, for embryos exposed under identical conditions and delivered the same absorbed dose of radiation, the response is significantly increased when shorter bursts of more energetic photons are used. These results suggest that biological organisms display properties similar to the photoelectric effect in physical systems and provide new insights into how radiation-mediated apoptosis should be understood and utilized for therapeutic purposes. PMID:20126466

Gamma-H2AX-based dose estimation for whole and partial body radiation exposure.

PubMed

Horn, Simon; Barnard, Stephen; Rothkamm, Kai

2011-01-01

Most human exposures to ionising radiation are partial body exposures. However, to date only limited tools are available for rapid and accurate estimation of the dose distribution and the extent of the body spared from the exposure. These parameters are of great importance for emergency triage and clinical management of exposed individuals. Here, measurements of γ-H2AX immunofluorescence by microscopy and flow cytometry were compared as rapid biodosimetric tools for whole and partial body exposures. Ex vivo uniformly X-irradiated blood lymphocytes from one donor were used to generate a universal biexponential calibration function for γ-H2AX foci/intensity yields per unit dose for time points up to 96 hours post exposure. Foci--but not intensity--levels remained significantly above background for 96 hours for doses of 0.5 Gy or more. Foci-based dose estimates for ex vivo X-irradiated blood samples from 13 volunteers were in excellent agreement with the actual dose delivered to the targeted samples. Flow cytometric dose estimates for X-irradiated blood samples from 8 volunteers were in excellent agreement with the actual dose delivered at 1 hour post exposure but less so at 24 hours post exposure. In partial body exposures, simulated by mixing ex vivo irradiated and unirradiated lymphocytes, foci/intensity distributions were significantly over-dispersed compared to uniformly irradiated lymphocytes. For both methods and in all cases the estimated fraction of irradiated lymphocytes and dose to that fraction, calculated using the zero contaminated Poisson test and γ-H2AX calibration function, were in good agreement with the actual mixing ratios and doses delivered to the samples. In conclusion, γ-H2AX analysis of irradiated lymphocytes enables rapid and accurate assessment of whole body doses while dispersion analysis of foci or intensity distributions helps determine partial body doses and the irradiated fraction size in cases of partial body exposures.

Correlation of tissue concentrations of the pyrethroid bifenthrin with neurotoxicity in the rat.

PubMed

Scollon, Edward J; Starr, James M; Crofton, Kevin M; Wolansky, Marcelo J; DeVito, Michael J; Hughes, Michael F

2011-11-28

The potential for human exposure to pyrethroid pesticides has prompted pharmacodynamic and pharmacokinetic research to better characterize risk. This work tested the hypothesis that blood and brain concentrations of the pyrethroid bifenthrin are predictive of neurotoxic effects. Adult male Long Evans rats received a single oral dose of bifenthrin dissolved in corn oil. Using figure-eight mazes, motor activity was measured for 1h at 4- and 7-h following exposure to bifenthrin (0-16mg/kg or 0-9mg/kg, respectively; n=4-8/group). Whole blood and brains were collected immediately following motor activity assays. Bifenthrin concentrations in blood and brain were quantified using HPLC/MS/MS. Bifenthrin exposure decreased motor activity from 20% to 70% in a dose-dependent manner at both time points. The relationship between motor activity data and administered dose, and blood and brain bifenthrin concentrations were described using a sigmoidal E(max) model. The relationships between motor activity and administered dose or blood concentrations were different between the 4- and 7-h time points. The relationship between motor activity and brain concentration was not significantly different between the two time points. These data suggest that momentary brain concentration of bifenthrin may be a more precise dose metric for predicting behavioral effects because the relationship between brain concentration and locomotor activity is independent of the time of exposure. Published by Elsevier Ireland Ltd.

Short and long-term exposure of CNS cell lines to BPA-f a radiosensitizer for boron neutron capture therapy: safety dose evaluation by a battery of cytotoxicity tests.

PubMed

De Simone, U; Manzo, L; Ferrari, C; Bakeine, J; Locatelli, C; Coccini, T

2013-03-01

Despite the current clinical use of boronophenylalanine-fructose (BPA-f), as radiosensitizer, in BNCT application for brain tumors, still remains to be determined the safety dose of this agent. We evaluated the potential risk of primary BPA-f toxicity before neutronic irradiation at different concentrations (0-100μgBeq/ml) after short- and long-term exposure (4-48h and 7-10 days), using a battery of tests (i.e. MTT assay, calcein-AM/Propidium Iodide staining, clonogenic test) in CNS cell models (D384 and SH-SY5Y), and non-neuronal primary human fibroblasts (F26). MTT data showed: (i) no cytotoxic effects after short-term exposure (4h) to any of BPA-f concentrations tested in all cell models; (ii) dose- and time-dependent mitochondrial activity impairment in D384 and SH-SY5Y cells only (with 60% and 40% cell death in D384 and SH-SY5Y, respectively, after 48h exposure to BPA-f 100μgBeq/ml). By Calcein-AM/PI staining, BPA-f treatment was specific toward SH-SY5Y cells only: a dose-dependent cell density reduction was observed, with a more pronounced effect after 48h exposure (15-40% at doses ranging 20-100μgBeq/ml). Clonogenic data revealed dose-dependent decrease of cell proliferative capacity in all cell lines, still the SH-SY5Y cells were the most sensitive ones: the lowest dose (20μgBeq/ml) produced 90% cell decrease. These results indicate dose- and time-dependent cytotoxic effects of BPA-f, with CNS cells showing a lower tolerance compared to fibroblasts. Long-term exposure to BPA-f compromised the proliferative capacity regardless of cell model type (cell sensitivity being SH-SY5Y>D384>F26). In short-time exposure, BPA-f exhibits a safe dosage up to 40μgBeq/ml for the viability of CNS cell lines. Copyright © 2012 Elsevier Inc. All rights reserved.

[Evaluation of radiation exposure of personnel in an orthopaedic and trauma operation theatre using the new real-time dosimetry system "dose aware"].

PubMed

Müller, M C; Strauss, A; Pflugmacher, R; Nähle, C P; Pennekamp, P H; Burger, C; Wirtz, D C

2014-08-01

There is a positive correlation between operation time and staff exposure to radiation during intraoperative use of C-arm fluoroscopy. Due to harmful effects of exposure to long-term low-dose radiation for both the patient and the operating team it should be kept to a minimum. AIM of this study was to evaluate a novel dosimeter system called Dose Aware® (DA) enabling radiation exposure feedback of the personal in an orthopaedic and trauma operation theatre in real-time. Within a prospective study over a period of four month, DA was applied by the operation team during 104 orthopaedic and trauma operations in which the C-arm fluoroscope was used in 2D-mode. During ten operation techniques, radiation exposure of the surgeon, the first assistant, the theatre nurse and the anaesthesiologist was evaluated. Seventy-three operations were analysed. The surgeon achieved the highest radiation exposure during dorsolumbar spinal osteosynthesis, kyphoplasty and screw fixation of sacral fractures. The first assistant received a higher radiation exposure compared to the surgeon during plate osteosynthesis of distal radius fractures (157 %), intramedullary nailing of pertrochanteric fractures (143 %) and dorsolumbar spinal osteosynthesis (240 %). During external fixation of ankle fractures (68 %) and screw fixation of sacral fractures (66 %) radiation exposure of the theatre nurse exceeded 50 % of the surgeon's radiation exposure. During plate osteosynthesis of distal radius fractures (157 %) and intramedullary splinting of clavicular fractures (115 %), the anaesthesiologist received a higher radiation exposure than the surgeon. The novel dosimeter system DA provides real-time radiation exposure feedback of the personnel in an orthopaedic and trauma operation theatre for the first time. Data of this study demonstrate that radiation exposure of the personnel depends on the operation type. The first assistant, the theatre nurse and the anaesthesiologist might be exposed to higher radiation doses than the surgeon. DA might help to increase awareness concerning irradiation in an orthopaedic and trauma operation theatre and might enhance staff compliance in using radiation protection techniques. Georg Thieme Verlag KG Stuttgart · New York.

The Effect of Realtime Monitoring on Dose Exposure to Staff Within an Interventional Radiology Setting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumann, Frederic, E-mail: fredericbaumann@hotmail.com; Katzen, Barry T.; Carelsen, Bart

PurposeThe purpose of this study is to evaluate a new device providing real-time monitoring on radiation exposure during fluoroscopy procedures intending to reduce radiation in an interventional radiology setting.Materials and MethodsIn one interventional suite, a new system providing a real-time radiation dose display and five individual wireless dosimeters were installed. The five dosimeters were worn by the attending, fellow, nurse, technician, and anesthesiologist for every procedure taking place in that suite. During the first 6-week interval the dose display was off (closed phase) and activated thereafter, for a 6-week learning phase (learning phase) and a 10-week open phase (open phase).more » During these phases, the staff dose and the individual dose for each procedure were recorded from the wireless dosimeter and correlated with the fluoroscopy time. Further subanalysis for dose exposure included diagnostic versus interventional as well as short (<10 min) versus long (>10 min) procedures.ResultsA total of 252 procedures were performed (n = 88 closed phase, n = 50 learning phase, n = 114 open phase). The overall mean staff dose per fluoroscopic minute was 42.79 versus 19.81 µSv/min (p < 0.05) comparing the closed and open phase. Thereby, anesthesiologists were the only individuals attaining a significant dose reduction during open phase 16.9 versus 8.86 µSv/min (p < 0.05). Furthermore, a significant reduction of total staff dose was observed for short 51 % and interventional procedures 45 % (p < 0.05, for both).ConclusionA real-time qualitative display of radiation exposure may reduce team radiation dose. The process may take a few weeks during the learning phase but appears sustained, thereafter.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The DOE Occupational Radiation Exposure Report, 1992-1994 reports occupational radiation exposures incurred by individuals at US Department of Energy (DOE) facilities from 1992 through 1994. This report includes occupational radiation exposure information for all DOE employees, contractors, subcontractors, and visitors. This information is analyzed and trended over time to provide a measure of the DOE`s performance in protecting its workers from radiation. Occupational radiation exposure at DOE has been decreasing over the past 5 years. In particular, doses in the higher dose ranges are decreasing, including the number of doses in excess of the DOE limits and doses in excessmore » of the 2 rem Administrative Control Level (ACL). This is an indication of greater attention being given to protecting these individuals from radiation in the workplace.« less

Analysis of Dose Response for Circulatory Disease After Radiotherapy for Benign Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Little, Mark P., E-mail: mark.little@nih.gov; Kleinerman, Ruth A.; Stovall, Marilyn

Purpose: To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy{sup -1} of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy{sup -1} of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. Theremore » were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.« less

Effect of dose rate on residual γ-H2AX levels and frequency of micronuclei in X-irradiated mouse lymphocytes.

PubMed

Turner, H C; Shuryak, I; Taveras, M; Bertucci, A; Perrier, J R; Chen, C; Elliston, C D; Johnson, G W; Smilenov, L B; Amundson, S A; Brenner, D J

2015-03-01

The biological risks associated with low-dose-rate (LDR) radiation exposures are not yet well defined. To assess the risk related to DNA damage, we compared the yields of two established biodosimetry end points, γ-H2AX and micronuclei (MNi), in peripheral mouse blood lymphocytes after prolonged in vivo exposure to LDR X rays (0.31 cGy/min) vs. acute high-dose-rate (HDR) exposure (1.03 Gy/min). C57BL/6 mice were total-body irradiated with 320 kVP X rays with doses of 0, 1.1, 2.2 and 4.45 Gy. Residual levels of total γ-H2AX fluorescence in lymphocytes isolated 24 h after the start of irradiation were assessed using indirect immunofluorescence methods. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptotic cell frequency in lymphocytes sampled at 24 h. Curve fitting analysis suggested that the dose response for γ-H2AX yields after acute exposures could be described by a linear dependence. In contrast, a linear-quadratic dose-response shape was more appropriate for LDR exposure (perhaps reflecting differences in repair time after different LDR doses). Dose-rate sparing effects (P < 0.05) were observed at doses ≤2.2 Gy, such that the acute dose γ-H2AX and TUNEL-positive cell yields were significantly larger than the equivalent LDR yields. At the 4.45 Gy dose there was no difference in γ-H2AX expression between the two dose rates, whereas there was a two- to threefold increase in apoptosis in the LDR samples compared to the equivalent 4.45 Gy acute dose. Micronuclei yields were measured at 24 h and 7 days using the in vitro cytokinesis-blocked micronucleus (CBMN) assay. The results showed that MNi yields increased up to 2.2 Gy with no further increase at 4.45 Gy and with no detectable dose-rate effect across the dose range 24 h or 7 days post exposure. In conclusion, the γ-H2AX biomarker showed higher sensitivity to measure dose-rate effects after low-dose LDR X rays compared to MNi formation; however, confounding factors such as variable repair times post exposure, increased cell killing and cell cycle block likely contributed to the yields of MNi with accumulating doses of ionizing radiation.

Collection of DICOM RDSR (Digital Imaging and Communication in Medicine, Radiation Dose Structured Report) Information Aimed at Reducing Patient Exposure Dose.

PubMed

Morota, Koichi; Moritake, Takashi; Sun, Lue; Ishihara, Takahiro; Kuma, Natsuyo; Murata, Satomi; Yamada, Takahiro; Okazaki, Ryuji

2016-01-01

The recent progress in angiography technology bestows benefits on patients for minimally invasive than surgery, while there has been an increase in the number of cases involving stochastic effects, such as radiation dermatitis, resulting from upgrading of the procedure because of an extension of the time for fluoroscopy and the number of shots. Recent CT equipment saves the dose data along with image data about the information management for patient exposure dose, which is used for management of individual cumulative dose and the presumed effective dose, using digital imaging and communication in medicine (DICOM). We extracted detailed information about shooting conditions and dose from the DICOM radiation dose structured report (DICOM RDSR) in the angiography area, and evaluated the trend of patient exposure dose in each procedure. As a result, we found that cases exceeding 3 Gy which needed observation in the head region were 16.7% and in the heart region were 27.3%. We also found that angiography had a higher dose of shooting than did fluoroscopy, and that the diagnosis and treatment with tumor involvement required a exposure dose than did vascular lesion. In this paper, we review the shooting conditions as a root of DICOM RDSR information and consider the possibility of planning for further reduction of the exposure dose.

American association of poison control centers database characterization of human tilmicosin exposures, 2001-2005.

PubMed

Oakes, Jennifer; Seifert, Steven

2008-12-01

Tilmicosin is a veterinary antibiotic with significant human toxicity at doses commonly used in animals, but the parenteral dose-response relationship has not been well characterized. Human exposures to tilmicosin in the database of the American Association of Poison Control Centers (AAPCC) from 2001 to 2005 were analyzed for demographic associations, exposure dose, clinical effects and outcomes. Over the 5-year period, there were 1,291 single-substance human exposures to tilmicosin. The mean age was 39.1 years, and 80% were male. By route there were 768 (54%) parenteral exposures. Patients with parenteral exposures had a significantly increased likelihood of being seen at a healthcare facility, admission, and admission to an ICU. With nonparenteral exposure, most had no clinical effects or minor effects, and there were no major effects or deaths. With parenteral exposure, moderate effects occurred in 46 (6%), major effects in 2 (0.3%) and there were 4 (0.5%) deaths, two of which were suicides. A dose-response relationship could be demonstrated. Clinical effect durations of up to a week occurred at even the lowest dose range. Over 250 cases of human tilmicosin exposure are reported to poison centers per year and over 150 of those are parenteral. Most exposures produce no or minor effects, but fatalities have occurred with parenteral exposure. The case fatality rate in parenteral exposures is 10 times the case fatality rate for all human exposures in the AAPCC database. Significant adverse and prolonged effects are reported at parenteral doses > 0.5 mL, suggesting that all parenteral exposures should be referred for healthcare facility evaluation.

The potential reproductive, neurobehavioral and systemic effects of soluble sodium tungstate exposure in Sprague-Dawley rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

McInturf, S.M.; Bekkedal, M.Y.V.; Wilfong, E.

2011-07-15

The debate on tungsten (W) is fostered by its continuous usage in military munitions. Reports demonstrate W solubilizes in soil and can migrate into drinking water supplies and, therefore, is a potential health risk to humans. This study evaluated the reproductive, systemic and neurobehavioral effects of sodium tungstate (NaW) in rats following 70 days of daily pre-and postnatal exposure via oral gavage to 5, 62.5 and 125 mg/kg/day of NaW through mating, gestation and weaning (PND 0-20). Daily administration of NaW produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development. Distressmore » vocalizations were elevated in F{sub 1} offspring from the high dose group, whereas righting reflex showed unexpected sex differences where males demonstrated faster righting than females; however, the effects were not dose-dependent. Locomotor activity was affected in both low and high-dose groups of F{sub 1} females. Low-dose group showed increased distance traveled, more time in ambulatory movements and less time in stereotypic behavior than controls or high dose animals. The high-dose group had more time in stereotypical movements than controls, and less time resting than controls and the lowest exposure group. Maternal retrieval was not affected by NaW exposure. Tungsten analysis showed a systemic distribution of NaW in both parents and offspring, with preferential uptake within the immune organs, including the femur, spleen and thymus. Histopathological evidence suggested no severe chronic injury or loss of function in these organs. However, the heart showed histological lesions, histiocytic inflammation from minimal to mild with cardiomyocyte degeneration and necrosis in several P{sub 0} animals of 125 mg NaW dose group. The result of this study suggests that pre and postnatal exposure to NaW may produce subtle neurobehavioral effects in offspring related to motor activity and emotionality.« less

Eye lens exposure to medical staff during endoscopic retrograde cholangiopancreatography.

PubMed

Zagorska, A; Romanova, K; Hristova-Popova, J; Vassileva, J; Katzarov, K

2015-11-01

The paper presents a study of the radiation doses to eye lens of medical staff during endoscopic retrograde cholangiopancreatography (ERCP) procedures performed in a busy gastroenterology department. For each procedure the dose equivalent to the eye, exposure time, dose rate, Kerma Area Product and fluoroscopy time were recorded. Measurements were performed for a period of two months in four main positions of the operating staff, and then extrapolated to estimate annual doses. The fluoroscopy time per ERCP procedure varied between 1.0 min and 28.8 min, with a mean value of 4.6 min. The calculated mean eye dose per procedure varied between 34.9 μSv and 93.3 μSv. The results demonstrated that if eye protection is not used, annual doses to the eye lens of the gastroenterologist performing the procedure and the anesthesiologist can exceed the dose limit of 20 mSv per year. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Emesis as a Screening Diagnostic for Low Dose Rate (LDR) Total Body Radiation Exposure.

PubMed

Camarata, Andrew S; Switchenko, Jeffrey M; Demidenko, Eugene; Flood, Ann B; Swartz, Harold M; Ali, Arif N

2016-04-01

Current radiation disaster manuals list the time-to-emesis (TE) as the key triage indicator of radiation dose. The data used to support TE recommendations were derived primarily from nearly instantaneous, high dose-rate exposures as part of variable condition accident databases. To date, there has not been a systematic differentiation between triage dose estimates associated with high and low dose rate (LDR) exposures, even though it is likely that after a nuclear detonation or radiologic disaster, many surviving casualties would have received a significant portion of their total exposure from fallout (LDR exposure) rather than from the initial nuclear detonation or criticality event (high dose rate exposure). This commentary discusses the issues surrounding the use of emesis as a screening diagnostic for radiation dose after LDR exposure. As part of this discussion, previously published clinical data on emesis after LDR total body irradiation (TBI) is statistically re-analyzed as an illustration of the complexity of the issue and confounding factors. This previously published data includes 107 patients who underwent TBI up to 10.5 Gy in a single fraction delivered over several hours at 0.02 to 0.04 Gy min. Estimates based on these data for the sensitivity of emesis as a screening diagnostic for the low dose rate radiation exposure range from 57.1% to 76.6%, and the estimates for specificity range from 87.5% to 99.4%. Though the original data contain multiple confounding factors, the evidence regarding sensitivity suggests that emesis appears to be quite poor as a medical screening diagnostic for LDR exposures.

Gene Expression Changes in Mouse Intestinal Tissue Following Whole-Body Proton or Gamma-Irradiation

NASA Technical Reports Server (NTRS)

Purgason, Ashley; Zhang, Ye; Mangala, Lingegowda; Nie, Ying; Gridley, Daila; Hamilton, Stanley R.; Seidel, Derek V.; Wu, Honglu

2014-01-01

Crew members face potential consequences following exposure to the space radiation environment including acute radiation syndrome and cancer. The space radiation environment is ample with protons, and numerous studies have been devoted to the understanding of the health consequences of proton exposures. In this project, C57BL/6 mice underwent whole-body exposure to 250 MeV of protons at doses of 0, 0.1, 0.5, 2 and 6 Gy and the gastrointestinal (GI) tract of each animal was dissected four hours post-irradiation. Standard H&E staining methods to screen for morphologic changes in the tissue showed an increase in apoptotic lesions for even the lowest dose of 0.1 Gy, and the percentage of apoptotic cells increased with increasing dose. Results of gene expression changes showed consistent up- or down- regulation, up to 10 fold, of a number of genes across exposure doses that may play a role in proton-induced oxidative stress including Gpx2. A separate study in C57BL/6 mice using the same four hour time point but whole-body gamma-irradiation showed damage to the small intestine with lesions appearing at the smallest dose of 0.05 Gy and increasing with increasing absorbed dose. Expressions of genes associated with oxidative stress processes were analyzed at four hours and twenty-four hours after exposure to gamma rays. We saw a much greater number of genes with significant up- or down-regulation twenty-four hours post-exposure as compared to the four hour time point. At both four hours and twenty-four hours post-exposure, Duox1 and Mpo underwent up-regulation for the highest dose of 6 Gy. Both protons and gamma rays lead to significant variation in gene expressions and these changes may provide insight into the mechanism of injury seen in the GI tract following radiation exposure. We have also completed experiments using a BALB/c mouse model undergoing whole-body exposure to protons. Doses of 0, 0.1, 1 and 2 Gy were used and results will be compared to the work mentioned above. The most striking result preliminarily is that both strains of mice show a greater number of genes changing at the lowest dose of exposure for their respective pathways.

Estimated UV doses to psoriasis patients during climate therapy at Gran Canaria in March 2006

NASA Astrophysics Data System (ADS)

Nilsen, L. T. N.; Søyland, E.; Krogstad, A. L.

2008-01-01

Psoriasis is a chronic inflammatory disease involving about 2-3% of the Norwegian population. Sun exposure has a positive effect on most psoriasis lesions, but ultraviolet (UV) radiation also causes a direct DNA damage in the skin cells and comprises a carcinogenic potential. UV exposure on the skin causes a local as well as a systemic immune suppressive effect, but the relation between sun exposure and these biological effects is not well known. In March 2006 a study was carried out to investigate possible therapeutic outcome mechanisms in 20 psoriasis patients receiving climate therapy at Gran Canaria. This paper presents estimates of their individual skin UV-doses based on UV measurements and the patients' diaries with information on time spent in the sun. On the first day of exposure the patients received on average 5.1 Standard Erythema Doses (SED: median=4.0 SED, range 2.6-10.3 SED) estimated to the skin. During the 15 days study they received 165.8 SED (range 104.3-210.1 SED). The reduction in PASI score was 72.8% on average, but there was no obvious relation between the improvement and the UV dose. The UV doses were higher than those found from climate therapy studies at other locations. It seems beneficial to use more strict exposure schedules that consider the available UV irradiance, depending on time of the day, time of the year and weather conditions.

Time and dose-response effects of honokiol on UVB-induced skin cancer development.

PubMed

Guillermo, Ruth F; Chilampalli, Chandeshwari; Zhang, Xiaoying; Zeman, David; Fahmy, Hesham; Dwivedi, Chandradhar

2012-06-01

Honokiol has shown chemopreventive effects in chemically-induced and UVB-induced skin cancer in mice. In this investigation, we assessed the time-effects of a topical low dose of honokiol (30 μg), and then the effects of different honokiol doses (30, 45, and 60 μg) on a UVB-induced skin cancer model to find an optimal dose and time for desirable chemopreventive effects. UVB radiation (30 mJ/cm(2), 5 days/week for 25 or 27 weeks) was used to induce skin carcinogenesis in SKH-1 mice. For the time-response experiment 30 μg honokiol in acetone was applied topically to the animals before the UVB exposure (30 min, 1 h, and 2 h) and after the UVB exposure (immediately, 30 min, and 1 h). Control groups were treated with acetone. For the dose-response study, animals were treated topically with acetone or honokiol (30, 45, and 60 μg) one hour before the UVB exposure. In the time-response experiment, honokiol inhibited skin tumor multiplicity by 49-58% while reducing tumor volumes by 70-89%. In the dose-response study, honokiol (30, 45, and 60 μg) significantly decreased skin tumor multiplicity by 36-78% in a dose-dependent manner, while tumor area was reduced by 76-94%. Honokiol (60 μg) significantly reduced tumor incidence by 40% as compared to control group. Honokiol applied in very low doses (30 μg) either before or after UVB radiation shows chemopreventive effects. Honokiol (30, 45, and 60 μg) prevents UVB-induced skin cancer in a dose-dependent manner. Honokiol can be an effective chemopreventive agent against skin cancer.

Modeling Rabbit Responses to Single and Multiple Aerosol ...

EPA Pesticide Factsheets

Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev

Toxicity of o,p′-DDE to medaka d-rR strain after a one-time embryonic exposure by in ovo nanoinjection: An early through juvenile life cycle assessment

USGS Publications Warehouse

Villalobos, Sergio A.; Papoulias, Diana M.; Pastva, Stephanie D.; Blankenship, Alan L.; Meadows, John C.; Tillitt, Donald E.; Giesy, John P.

2003-01-01

The toxicity of o,p′-DDE (1,1-dichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl) ethylene) was evaluated in embryos of medaka (Oryzias latipes) following a one time exposure via nanoinjection. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of 4 graded doses (0.0005-0.5 ng/egg) of o,p′-DDE in triolein. Embryos were allowed to develop, and fry were reared. Embryonic survival was monitored daily during the first 10 d until hatching and thereafter, on a weekly basis until day 59, at which time the fish were monitored for sexual maturity until day 107. In general, o,p′-DDE caused a dose- and time-dependent mortality. No changes in mortality were observed between the last two time points (day 38 and 59, respectively), and hence a 59 day-LD50 of 346 ng o,p′-DDE/egg was derived from the linear dose-response relationship. Prior to late stage death, only isolated cases of cardiovascular lesions and spinal deformities were observed, but were not dose-dependent. The lowest observable adverse effect level (LOAEL), based on upper 95% CI for regression line=0.0018 mg/kg, and the LOAEL based on exposure doses=0.5 mg/kg. Likewise, the no observable adverse effect level (NOAEL) based on linear extrapolation to 100% survival=0.0000388 mg/kg, while the NOAEL based on exposure doses=0.05 mg/kg. The nanoinjection medaka model has potential in the study of hormonally active compounds in the environment.

Expression of Genes Associated with DNA Damage Sensing in Human Fibroblasts Exposed to Low-dose-rate Gamma Rays

NASA Technical Reports Server (NTRS)

Zhang, Ye; Mehta, Satish; Hammond, Diane; Pierson, Duane; Jeevarajan, Antony; Cucinotta, Francis; Rohde, Larry; Wu, Honglu

2007-01-01

Understanding of the molecular response to low-dose and low-dose-rate radiation exposure is essential for the extrapolation of high-dose radiation risks to those at dose levels relevant to space and other environmental concerns. Most of the reported studies of gene expressions induced by low-dose or low-dose-rate radiation were carried out on exponentially growing cells. In the present study, we analyzed expressions of 84 genes associated with DNA damage sensing using real time PCR in human fibroblasts in mostly G1 phase of the cell cycle. The cells were exposed continuously to gamma rays at a dose rate of 0.8 cGy/hr for 1, 2, 6 or 24 hrs at 37 C throughout the exposure. The total RNA was isolated immediately after the exposure was terminated. Of the 84 genes, only a few showed significant changes of the expression level. Some of the genes (e.g. DDit3 and BTG2) were found to be up or down regulated only after a short period of exposure, while other genes (e.g. PRKDC) displayed a highest expression level at the 24 hr time point. The expression profiles for the exposed cells which had a smaller portion of G1 cells indicated more cell cycle signaling and DNA repair genes either up or down regulated. Interestingly, the panel of genes changed from radiation exposure in G1 cells is different from the panel in cells having less G1 arrest cells. The gene expression profile of the cells responding to low-dose-radiation insult apparently depends on the cell growth stage. The response pathway in G1 cells may differ from that in exponentially growing cells.

ESTIMATING CHILDREN'S DERMAL AND NON-DIETARY INGESTION EXPOSURE AND DOSE WITH EPA'S SHEDS MODEL

EPA Science Inventory

A physically-based stochastic model (SHEDS) has been developed to estimate pesticide exposure and dose to children via dermal residue contact and non-dietary ingestion. Time-location-activity data are sampled from national survey results to generate a population of simulated ch...

Comparison of modeled estimates of inhalation exposure to aerosols during use of consumer spray products.

PubMed

Park, Jihoon; Yoon, Chungsik; Lee, Kiyoung

2018-05-30

In the field of exposure science, various exposure assessment models have been developed to complement experimental measurements; however, few studies have been published on their validity. This study compares the estimated inhaled aerosol doses of several inhalation exposure models to experimental measurements of aerosols released from consumer spray products, and then compares deposited doses within different parts of the human respiratory tract according to deposition models. Exposure models, including the European Center for Ecotoxicology of Chemicals Targeted Risk Assessment (ECETOC TRA), the Consumer Exposure Model (CEM), SprayExpo, ConsExpo Web and ConsExpo Nano, were used to estimate the inhaled dose under various exposure scenarios, and modeled and experimental estimates were compared. The deposited dose in different respiratory regions was estimated using the International Commission on Radiological Protection model and multiple-path particle dosimetry models under the assumption of polydispersed particles. The modeled estimates of the inhaled doses were accurate in the short term, i.e., within 10 min of the initial spraying, with a differences from experimental estimates ranging from 0 to 73% among the models. However, the estimates for long-term exposure, i.e., exposure times of several hours, deviated significantly from the experimental estimates in the absence of ventilation. The differences between the experimental and modeled estimates of particle number and surface area were constant over time under ventilated conditions. ConsExpo Nano, as a nano-scale model, showed stable estimates of short-term exposure, with a difference from the experimental estimates of less than 60% for all metrics. The deposited particle estimates were similar among the deposition models, particularly in the nanoparticle range for the head airway and alveolar regions. In conclusion, the results showed that the inhalation exposure models tested in this study are suitable for estimating short-term aerosol exposure (within half an hour), but not for estimating long-term exposure. Copyright © 2018 Elsevier GmbH. All rights reserved.

Induction of genomic instability after an acute whole-body exposure of mice to 56Fe ions

NASA Astrophysics Data System (ADS)

Rithidech, Kanokporn Noy; Supanpaiboon, Wisa; Honikel, Louise; Whorton, Elbert B.

2009-10-01

The purpose of this study was to evaluate dose-response relationships for the in vivo induction of micronuclei (MN) as a measure of both initial radiation damage and the induction of genomic instability. These measurements were made in mouse blood erythrocytes as a function of radiation dose, radiation quality, time after irradiation, and the genetic background of exposed individuals. Blood samples were collected from two strains of mouse (CBA/CaJ and C57BL/6J) at different times up to 3 months following a whole-body exposure to various doses of 1 GeV/amu 56Fe ions (0, 0.1, 0.5 and 1.0 Gy, at the dose rate of a 1 Gy/min) or 137Cs gamma rays (0, 0.5, 1.0 and 3.0 Gy, at the dose rate of 0.72 Gy/min). Blood-smear slides were stained with acridine orange (AO). The frequencies of MN were measured in mature normochromatic-erythrocytes (MN-NCEs) and in immature polychromatic-erythrocytes (MN-PCEs). Effects of both types of radiation on erythropoiesis were also evaluated. As a measure of cell progression delay, a dose-dependent decrease in numbers of PCEs was observed at day 2 post-exposure in both strains, regardless of radiation quality. Subsequently, the levels of PCEs increased in all exposed mice, reaching control levels (or higher) by day 7 post-exposure. Further, at day 2 after the exposure, there was no increase in the frequency of MN-PCEs in CBA/CaJ mice exposed to 56Fe ions while the frequency of MN-PCEs elevated as a function of dose in the C57BL/6J mice. At day 4, there was no dose related increase in MN-NCEs in either strain of mouse exposed to 137Cs gamma rays. Additionally, at the early sacrifice times (days 2 and 4), 56Fe ions were slightly more effective (per unit dose) in inducing MN-NCEs than 137Cs gamma rays in CBA/CaJ mice. However, there was no increase in the frequency of MN-NCEs at late times after an acute exposure to either type of radiation. In contrast, both types of radiation induced increased MN-PCEs frequencies in irradiated CBA/CaJ mice, but not C57BL/6J mice, at late times post-exposure. This finding indicates the potential induction of genomic instability in hematopoietic cells of CBA/CaJ mice by both types of radiation. The finding also demonstrates the influence of genetic background on radiation-induced genomic instability in vivo.

[Radiation exposure of radiologists during angiography: dose measurements outside the lead apron].

PubMed

Fischer, H; Przetak, C; Teubert, G; Ewen, K; Mödder, U

1995-02-01

The aim of this study was to provide practical information to angiographers concerning radiation exposure to body parts not covered by lead aprons. Individual doses to the neck and hands of radiologists measured in micro-Sieverts were obtained during the course of 80 angiographies of various types. The number of diagnostic and interventional procedures, which might lead to exceeding permissible doses, have been calculated. Possibilities of estimating doses during angiography by means of parameters such as screening times were examined statistically. Especially with regard to the hands, estimations of the doses are insufficient (correlation r = 0.21). Radiologists who undertake much angiographic and particularly interventional work may reach exposure levels requiring protective measures in addition to lead aprons.

Time- and dose-dependent changes in neuronal activity produced by X radiation in brain slices.

PubMed

Pellmar, T C; Schauer, D A; Zeman, G H

1990-05-01

A new method of exposing tissues to X rays in a lead Faraday cage has made it possible to examine directly radiation damage to isolated neuronal tissue. Thin slices of hippocampus from brains of euthanized guinea pigs were exposed to 17.4 ke V X radiation. Electrophysiological recordings were made before, during, and after exposure to doses between 5 and 65 Gy at a dose rate of 1.54 Gy/min. Following exposure to doses of 40 Gy and greater, the synaptic potential was enhanced, reaching a steady level soon after exposure. The ability of the synaptic potential to generate a spike was reduced and damage progressed after termination of the radiation exposure. Recovery was not observed following termination of exposure. These results demonstrate that an isolated neuronal network can show complex changes in electrophysiological properties following moderate doses of ionizing radiation. An investigation of radiation damage directly to neurons in vitro will contribute to the understanding of the underlying mechanisms of radiation-induced nervous system dysfunction.

Prediction of Drug-Drug Interactions with Crizotinib as the CYP3A Substrate Using a Physiologically Based Pharmacokinetic Model.

PubMed

Yamazaki, Shinji; Johnson, Theodore R; Smith, Bill J

2015-10-01

An orally available multiple tyrosine kinase inhibitor, crizotinib (Xalkori), is a CYP3A substrate, moderate time-dependent inhibitor, and weak inducer. The main objectives of the present study were to: 1) develop and refine a physiologically based pharmacokinetic (PBPK) model of crizotinib on the basis of clinical single- and multiple-dose results, 2) verify the crizotinib PBPK model from crizotinib single-dose drug-drug interaction (DDI) results with multiple-dose coadministration of ketoconazole or rifampin, and 3) apply the crizotinib PBPK model to predict crizotinib multiple-dose DDI outcomes. We also focused on gaining insights into the underlying mechanisms mediating crizotinib DDIs using a dynamic PBPK model, the Simcyp population-based simulator. First, PBPK model-predicted crizotinib exposures adequately matched clinically observed results in the single- and multiple-dose studies. Second, the model-predicted crizotinib exposures sufficiently matched clinically observed results in the crizotinib single-dose DDI studies with ketoconazole or rifampin, resulting in the reasonably predicted fold-increases in crizotinib exposures. Finally, the predicted fold-increases in crizotinib exposures in the multiple-dose DDI studies were roughly comparable to those in the single-dose DDI studies, suggesting that the effects of crizotinib CYP3A time-dependent inhibition (net inhibition) on the multiple-dose DDI outcomes would be negligible. Therefore, crizotinib dose-adjustment in the multiple-dose DDI studies could be made on the basis of currently available single-dose results. Overall, we believe that the crizotinib PBPK model developed, refined, and verified in the present study would adequately predict crizotinib oral exposures in other clinical studies, such as DDIs with weak/moderate CYP3A inhibitors/inducers and drug-disease interactions in patients with hepatic or renal impairment. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Modeling cumulative dose and exposure duration provided insights regarding the associations between benzodiazepines and injuries.

PubMed

Abrahamowicz, Michal; Bartlett, Gillian; Tamblyn, Robyn; du Berger, Roxane

2006-04-01

Accurate assessment of medication impact requires modeling cumulative effects of exposure duration and dose; however, postmarketing studies usually represent medication exposure by baseline or current use only. We propose new methods for modeling various aspects of medication use history and employment of them to assess the adverse effects of selected benzodiazepines. Time-dependent measures of cumulative dose or duration of use, with weighting of past exposures by recency, were proposed. These measures were then included in alternative versions of the multivariable Cox model to analyze the risk of fall related injuries among the elderly new users of three benzodiazepines (nitrazepam, temazepam, and flurazepam) in Quebec. Akaike's information criterion (AIC) was used to select the most predictive model for a given benzodiazepine. The best-fitting model included a combination of cumulative duration and current dose for temazepam, and cumulative dose for flurazepam and nitrazepam, with different weighting functions. The window of clinically relevant exposure was shorter for flurazepam than for the two other products. Careful modeling of the medication exposure history may enhance our understanding of the mechanisms underlying their adverse effects.

Predictive dose-based estimation of systemic exposure multiples in mouse and monkey relative to human for antisense oligonucleotides with 2'-o-(2-methoxyethyl) modifications.

PubMed

Yu, Rosie Z; Grundy, John S; Henry, Scott P; Kim, Tae-Won; Norris, Daniel A; Burkey, Jennifer; Wang, Yanfeng; Vick, Andrew; Geary, Richard S

2015-01-20

Evaluation of species differences and systemic exposure multiples (or ratios) in toxicological animal species versus human is an ongoing exercise during the course of drug development. The systemic exposure ratios are best estimated by directly comparing area under the plasma concentration-time curves (AUCs), and sometimes by comparing the dose administered, with the dose being adjusted either by body surface area (BSA) or body weight (BW). In this study, the association between AUC ratio and the administered dose ratio from animals to human were studied using a retrospective data-driven approach. The dataset included nine antisense oligonucleotides (ASOs) with 2'-O-(2-methoxyethyl) modifications, evaluated in two animal species (mouse and monkey) following single and repeated parenteral administrations. We found that plasma AUCs were similar between ASOs within the same species, and are predictable to human exposure using a single animal species, either mouse or monkey. Between monkey and human, the plasma exposure ratio can be predicted directly based on BW-adjusted dose ratios, whereas between mouse and human, the exposure ratio would be nearly fivefold lower in mouse compared to human based on BW-adjusted dose values. Thus, multiplying a factor of 5 for the mouse BW-adjusted dose would likely provide a reasonable AUC exposure estimate in human at steady-state.

RADIATION DOSES AND CANCER RISKS IN THE MARSHALL ISLANDS ASSOCIATED WITH EXPOSURE TO RADIOACTIVE FALLOUT FROM BIKINI AND ENEWETAK NUCLEAR WEAPONS TESTS: SUMMARY

PubMed Central

Simon, Steven L.; Bouville, André; Land, Charles E.; Beck, Harold L.

2014-01-01

Nuclear weapons testing conducted at Bikini and Enewetak Atolls during 1946–1958 resulted in exposures of the resident population of the present-day Republic of the Marshall Islands to radioactive fallout. This paper summarizes the results of a thorough and systematic reconstruction of radiation doses to that population, by year, age at exposure, and atoll of residence, and the related cancer risks. Detailed methods and results are presented in a series of companion papers in this volume. From our analysis, we concluded that 20 of the 66 nuclear tests conducted in or near the Marshall Islands resulted in measurable fallout deposition on one or more of the inhabited atolls of the Marshall Islands. In this work, we estimated deposition densities (kBq m−2) of all important dose-contributing radionuclides at each of the 32 atolls and separate reef islands of the Marshall Islands. Quantitative deposition estimates were made for 63 radionuclides from each test at each atoll. Those estimates along with reported measurements of exposure rates at various times after fallout were used to estimate radiation absorbed doses to the red bone marrow, thyroid gland, stomach wall, and colon wall of atoll residents from both external and internal exposure. Annual doses were estimated for six age groups ranging from newborns to adults. We found that the total deposition of 137Cs, external dose, internal organ doses, and cancer risks followed the same geographic pattern with the large population of the southern atolls receiving the lowest doses. Permanent residents of the southern atolls who were of adult age at the beginning of the testing period received external doses ranging from 5 to 12 mGy on average; the external doses to adults at the mid-latitude atolls ranged from 22 to 59 mGy on average, while the residents of the northern atolls received external doses in the hundreds to over 1,000 mGy. Internal doses varied significantly by age at exposure, location, and organ. Except for internal doses to the thyroid gland, external exposure was generally the major contributor to organ doses, particularly for red bone marrow and stomach wall. Internal doses to the stomach wall and red bone marrow were similar in magnitude, about 1 mGy to 7 mGy for permanent residents of the southern and mid-latitude atolls. However, adult residents of Utrik and Rongelap Island, which are part of the northern atolls, received much higher internal doses because of intakes of short-lived radionuclides leading to doses from 20 mGy to more than 500 mGy to red bone marrow and stomach wall. In general, internal doses to the colon wall were four to ten times greater than those to the red bone marrow and internal doses to the thyroid gland were 20 to 30 times greater than to the red bone marrow. Adult internal thyroid doses for the Utrik community and for the Rongelap Island community were about 760 mGy and 7,600 mGy, respectively. The highest doses were to the thyroid glands of young children exposed on Rongelap at the time of the Castle Bravo test of 1 March 1954 and were about three times higher than for adults. Internal doses from chronic intakes, related to residual activities of long-lived radionuclides in the environment, were, in general, low in comparison with acute exposure resulting from the intakes of radionuclides immediately or soon after the deposition of fallout. The annual doses and the population sizes at each atoll in each year were used to develop estimates of cancer risks for the permanent residents of all atolls that were inhabited during the testing period as well as for the Marshallese population groups that were relocated prior to the testing or after it had begun. About 170 excess cancers (radiation-related cases) are projected to occur among more than 25,000 Marshallese, half of whom were born before 1948. All but about 65 of those cancers are estimated to have already been expressed. The 170 excess cancers are in comparison to about 10,600 cancers that would spontaneously arise, unrelated to radioactive fallout, among the same cohort of Marshallese people. PMID:20622547

Radiation doses and cancer risks in the Marshall Islands associated with exposure to radioactive fallout from Bikini and Enewetak nuclear weapons tests: summary.

PubMed

Simon, Steven L; Bouville, André; Land, Charles E; Beck, Harold L

2010-08-01

Nuclear weapons testing conducted at Bikini and Enewetak Atolls during 1946-1958 resulted in exposures of the resident population of the present-day Republic of the Marshall Islands to radioactive fallout. This paper summarizes the results of a thorough and systematic reconstruction of radiation doses to that population, by year, age at exposure, and atoll of residence, and the related cancer risks. Detailed methods and results are presented in a series of companion papers in this volume. From our analysis, we concluded that 20 of the 66 nuclear tests conducted in or near the Marshall Islands resulted in measurable fallout deposition on one or more of the inhabited atolls of the Marshall Islands. In this work, we estimated deposition densities (kBq m(-2)) of all important dose-contributing radionuclides at each of the 32 atolls and separate reef islands of the Marshall Islands. Quantitative deposition estimates were made for 63 radionuclides from each test at each atoll. Those estimates along with reported measurements of exposure rates at various times after fallout were used to estimate radiation absorbed doses to the red bone marrow, thyroid gland, stomach wall, and colon wall of atoll residents from both external and internal exposure. Annual doses were estimated for six age groups ranging from newborns to adults. We found that the total deposition of 137Cs, external dose, internal organ doses, and cancer risks followed the same geographic pattern with the large population of the southern atolls receiving the lowest doses. Permanent residents of the southern atolls who were of adult age at the beginning of the testing period received external doses ranging from 5 to 12 mGy on average; the external doses to adults at the mid-latitude atolls ranged from 22 to 59 mGy on average, while the residents of the northern atolls received external doses in the hundreds to over 1,000 mGy. Internal doses varied significantly by age at exposure, location, and organ. Except for internal doses to the thyroid gland, external exposure was generally the major contributor to organ doses, particularly for red bone marrow and stomach wall. Internal doses to the stomach wall and red bone marrow were similar in magnitude, about 1 mGy to 7 mGy for permanent residents of the southern and mid-latitude atolls. However, adult residents of Utrik and Rongelap Island, which are part of the northern atolls, received much higher internal doses because of intakes of short-lived radionuclides leading to doses from 20 mGy to more than 500 mGy to red bone marrow and stomach wall. In general, internal doses to the colon wall were four to ten times greater than those to the red bone marrow and internal doses to the thyroid gland were 20 to 30 times greater than to the red bone marrow. Adult internal thyroid doses for the Utrik community and for the Rongelap Island community were about 760 mGy and 7,600 mGy, respectively. The highest doses were to the thyroid glands of young children exposed on Rongelap at the time of the Castle Bravo test of 1 March 1954 and were about three times higher than for adults. Internal doses from chronic intakes, related to residual activities of long-lived radionuclides in the environment, were, in general, low in comparison with acute exposure resulting from the intakes of radionuclides immediately or soon after the deposition of fallout. The annual doses and the population sizes at each atoll in each year were used to develop estimates of cancer risks for the permanent residents of all atolls that were inhabited during the testing period as well as for the Marshallese population groups that were relocated prior to the testing or after it had begun. About 170 excess cancers (radiation-related cases) are projected to occur among more than 25,000 Marshallese, half of whom were born before 1948. All but about 65 of those cancers are estimated to have already been expressed. The 170 excess cancers are in comparison to about 10,600 cancers that would spontaneously arise, unrelated to radioactive fallout, among the same cohort of Marshallese people.

Cosmic Radiation Exposure of Future Hypersonic Flight Missions.

PubMed

Koops, L

2017-06-15

Cosmic radiation exposure in air traffic grows with flight altitude, geographical latitude and flight time. For future high-speed intercontinental point-to-point travel, the trade-off between reduced flight time and enhanced dose rate at higher flight altitudes is investigated. Various representative (partly) hypersonic cruise missions are considered and in dependence on solar activity the integral route dose is calculated for envisaged flight profiles and trajectories. Our results are compared to those for corresponding air connections served by present day subsonic airliners. During solar maximum, we find a significant reduction in route dose for all considered high-speed missions compared to the subsonic reference. However, during solar minimum, comparable or somewhat larger doses result on transpolar trajectories with (partly) hypersonic cruise at Mach 5. Both solar activity and routing are hence found to determine, whether passengers can profit from shorter flight times in terms of radiation exposure, despite of altitude-induced higher dose rates. Yet, aircrews with fixed number of block hours are always subject to larger annual doses, which in the considered cases take values up to five times the reference. We comment on the implications of our results for route planning and aviation decision-making in the absence of radiation shielding solutions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

N-Acetyl Cysteine does not prevent liver toxicity from chronic low dose plus sub-acute high dose paracetamol exposure in young or old mice

PubMed Central

Kane, Alice-Elizabeth; Huizer-Pajkos, Aniko; Mach, John; McKenzie, Catriona; Mitchell, Sarah-Jayne; de Cabo, Rafael; Jones, Brett; Cogger, Victoria; Le Couteur, David G; Hilmer, Sarah-Nicole

2016-01-01

Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute over-exposures. The risk of hepatotoxicity from non-acute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for non-acute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and sub-acute paracetamol over-exposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures. Young and old male C57BL/6 mice were fed a paracetamol-containing (1.33g/kg food) or control diet for 6 weeks. Mice were then dosed orally 8 times over 3 days with additional paracetamol (250mg/kg) or saline, followed by either one or two doses of oral NAC (1200mg/kg) or saline. Chronic low-dose paracetamol exposure did not cause hepatotoxicity in young or old mice, measured by serum alanine aminotransferase (ALT) elevation, and confirmed by histology and a DNA fragmentation assay. Sub-acute paracetamol exposure caused significant hepatotoxicity in young and old mice, measured by biochemistry (ALT) and histology. Neither a single nor double dose of NAC protected against this toxicity from sub-acute paracetamol in young or old mice. This finding has important clinical implications for treating toxicity due to different paracetamol exposure types in patients of all ages, and implies a need to develop new treatments for sub-acute paracetamol toxicity. PMID:26821200

Airline Pilot Cosmic Radiation and Circadian Disruption Exposure Assessment from Logbooks and Company Records

PubMed Central

Grajewski, Barbara; Waters, Martha A.; Yong, Lee C.; Tseng, Chih-Yu; Zivkovich, Zachary; Cassinelli II, Rick T.

2011-01-01

Objectives: US commercial airline pilots, like all flight crew, are at increased risk for specific cancers, but the relation of these outcomes to specific air cabin exposures is unclear. Flight time or block (airborne plus taxi) time often substitutes for assessment of exposure to cosmic radiation. Our objectives were to develop methods to estimate exposures to cosmic radiation and circadian disruption for a study of chromosome aberrations in pilots and to describe workplace exposures for these pilots. Methods: Exposures were estimated for cosmic ionizing radiation and circadian disruption between August 1963 and March 2003 for 83 male pilots from a major US airline. Estimates were based on 523 387 individual flight segments in company records and pilot logbooks as well as summary records of hours flown from other sources. Exposure was estimated by calculation or imputation for all but 0.02% of the individual flight segments’ block time. Exposures were estimated from questionnaire data for a comparison group of 51 male university faculty. Results: Pilots flew a median of 7126 flight segments and 14 959 block hours for 27.8 years. In the final study year, a hypothetical pilot incurred an estimated median effective dose of 1.92 mSv (absorbed dose, 0.85 mGy) from cosmic radiation and crossed 362 time zones. This study pilot was possibly exposed to a moderate or large solar particle event a median of 6 times or once every 3.7 years of work. Work at the study airline and military flying were the two highest sources of pilot exposure for all metrics. An index of work during the standard sleep interval (SSI travel) also suggested potential chronic sleep disturbance in some pilots. For study airline flights, median segment radiation doses, time zones crossed, and SSI travel increased markedly from the 1990s to 2003 (Ptrend < 0.0001). Dose metrics were moderately correlated with records-based duration metrics (Spearman’s r = 0.61–0.69). Conclusions: The methods developed provided an exposure profile of this group of US airline pilots, many of whom have been exposed to increasing cosmic radiation and circadian disruption from the 1990s through 2003. This assessment is likely to decrease exposure misclassification in health studies. PMID:21610083

Airline pilot cosmic radiation and circadian disruption exposure assessment from logbooks and company records.

PubMed

Grajewski, Barbara; Waters, Martha A; Yong, Lee C; Tseng, Chih-Yu; Zivkovich, Zachary; Cassinelli, Rick T

2011-06-01

US commercial airline pilots, like all flight crew, are at increased risk for specific cancers, but the relation of these outcomes to specific air cabin exposures is unclear. Flight time or block (airborne plus taxi) time often substitutes for assessment of exposure to cosmic radiation. Our objectives were to develop methods to estimate exposures to cosmic radiation and circadian disruption for a study of chromosome aberrations in pilots and to describe workplace exposures for these pilots. Exposures were estimated for cosmic ionizing radiation and circadian disruption between August 1963 and March 2003 for 83 male pilots from a major US airline. Estimates were based on 523 387 individual flight segments in company records and pilot logbooks as well as summary records of hours flown from other sources. Exposure was estimated by calculation or imputation for all but 0.02% of the individual flight segments' block time. Exposures were estimated from questionnaire data for a comparison group of 51 male university faculty. Pilots flew a median of 7126 flight segments and 14 959 block hours for 27.8 years. In the final study year, a hypothetical pilot incurred an estimated median effective dose of 1.92 mSv (absorbed dose, 0.85 mGy) from cosmic radiation and crossed 362 time zones. This study pilot was possibly exposed to a moderate or large solar particle event a median of 6 times or once every 3.7 years of work. Work at the study airline and military flying were the two highest sources of pilot exposure for all metrics. An index of work during the standard sleep interval (SSI travel) also suggested potential chronic sleep disturbance in some pilots. For study airline flights, median segment radiation doses, time zones crossed, and SSI travel increased markedly from the 1990s to 2003 (P(trend) < 0.0001). Dose metrics were moderately correlated with records-based duration metrics (Spearman's r = 0.61-0.69). The methods developed provided an exposure profile of this group of US airline pilots, many of whom have been exposed to increasing cosmic radiation and circadian disruption from the 1990s through 2003. This assessment is likely to decrease exposure misclassification in health studies.

AN ESTIMATION OF THE EXPOSURE OF THE POPULATION OF ISRAEL TO NATURAL SOURCES OF IONIZING RADIATION.

PubMed

Epstein, L; Koch, J; Riemer, T; Haquin, G; Orion, I

2017-11-01

The radiation dose to the population of Israel due to exposure to natural sources of ionizing radiation was assessed. The main contributor to the dose is radon that accounts for 60% of the exposure to natural sources. The dose due to radon inhalation was assessed by combining the results of a radon survey in single-family houses with the results of a survey in apartments in multi-storey buildings. The average annual dose due to radon inhalation was found to be 1.2 mSv. The dose rate due to exposure to cosmic radiation was assessed using a code that calculates the dose rate at different heights above sea level, taking into account the solar cycle. The annual dose was calculated based on the fraction of time spent indoors and the attenuation provided by buildings and was found to be 0.2 mSv. The annual dose due to external exposure to the terrestrial radionuclides was similarly assessed. The indoor dose rate was calculated using a model that takes into account the concentrations of the natural radionuclides in building materials, the density and the thickness of the walls. The dose rate outdoors was calculated based on the concentrations of the natural radionuclides in different geological units in Israel as measured in an aerial survey and measurements above ground. The annual dose was found to be 0.2 mSv. Doses due to internal exposure other than exposure to radon were also calculated and were found to be 0.4 mSv. The overall annual exposure of the population of Israel to natural sources of ionizing radiation is therefore 2 mSv and ranges between 1.7 and 2.7 mSv. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Toxicokinetics of the flame retardant hexabromocyclododecane gamma: effect of dose, timing, route, repeated exposure, and metabolism.

PubMed

Szabo, David T; Diliberto, Janet J; Hakk, Heldur; Huwe, Janice K; Birnbaum, Linda S

2010-10-01

Hexabromocyclododecane-gamma (γ-HBCD) is the predominate diastereoisomer in the commercial HBCD mixture used as a flame retardant in a wide variety of consumer products. Three main diastereoisomers, alpha (α), beta (β), and gamma (γ), comprise the mixture. Despite the γ-diastereoisomer being the major diastereoisomer in the mixture and environmental samples, the α-diastereoisomer predominates human tissue and wildlife. This study was conducted to characterize absorption, distribution, metabolism, and excretion parameters of γ-HBCD with respect to dose and time following a single acute exposure and repeated exposure in adult female C57BL/6 mice. Results suggest that 85% of the administered dose (3 mg/kg) was absorbed after po exposure. Disposition was dose independent and did not significantly change after 10 days of exposure. Liver was the major depot (< 0.3% of dose) 4 days after treatment followed by blood, fat, and then brain. γ-HBCD was rapidly metabolized and eliminated in the urine and feces. For the first time, in vivo stereoisomerization was observed of the γ-diastereoisomer to the β-diastereoisomer in liver and brain tissues and to the α- and β-diastereoisomer in fat and feces. Polar metabolites in the blood and urine were a major factor in determining the initial whole-body half-life (1 day) after a single po exposure. Elimination, both whole-body and from individual tissues, was biphasic. Initial half-lives were approximately 1 day, whereas terminal half-lives were up to 4 days, suggesting limited potential for γ-diastereoisomer bioaccumulation. The toxicokinetic behavior reported here has important implications for the extrapolation of toxicological studies of the commercial HBCD mixture to the assessment of risk.

Exposure of medical staff to radiation during osteosynthesis of proximal femoral fracture: descriptive analysis and comparison of different devices.

PubMed

Siedlecki, Cédric; Gauthé, Rémi; Gillibert, André; Bellenger, Kevin; Roussignol, Xavier; Ould-Slimane, Mourad

2017-10-01

The use of fluoroscopy is necessary during proximal femoral fracture (PFF) osteosynthesis. The frequency of these procedures justifies a description of radiation exposure and comparisons between different techniques and between the different surgical team members. This observational prospective and comparative study includes a series of 68 patients with PFF receiving osteosynthesis. Radiation exposure was assessed for all members of the operating team. The radiation dose measurements for the different members of the surgical team during PFF osteosynthesis were compared. The factors affecting the radiation dose were investigated. The mean active dosimeter readings for each operation were 7.39 µSv for the primary surgeon, 3.93 µSv for the assistant surgeon, 1.92 µSv for the instrument nurse, 1.25 µSv for the circulating nurse, and 0.64 µSv for the anaesthesiologist, respectively. Doses decreased significantly between these different members of the medical team (all p < 0.001). The dose also varied with patient age and BMI, as well as with fluoroscopy time and operating time, but not with type of fracture or type of osteosynthesis. Medical staff receives significantly different doses depending on their position in relation to the radiation source. Operating time and fluoroscopy time are the modifiable factors that affect the radiation dose. The radiation doses received by the different members of the medical teams involved in proximal femur osteosynthesis procedures all fall below the doses recommended by the International Commission on Radiation Units and Measurements.

ASSESSING ASTHMATIC CHILDREN'S EXPOSURES TO TOXIC AIR POLLUTANTS AND THE POTENTIAL INHALED DOSES USING TIME ACTIVITY INFORMATION AND ENERGY EXPENDITURE DATA

EPA Science Inventory

Accurately quantifying human exposures and the potential doses of various populations to environmental pollutants is critical for the U.S. Environmental Protection Agency to assess and manage human health risks. The Tampa Asthmatic Children's Study (TACS) was a pilot research stu...

Licensure strategy for pre- and post-exposure prophylaxis of biothrax vaccine: the first vaccine licensed using the FDA animal rule.

PubMed

Longstreth, Janice; Skiadopoulos, Mario H; Hopkins, Robert J

2016-12-01

The availability of a licensed anthrax vaccine that is safe, effective, and easy to administer for both pre- and post-exposure prophylaxis is critical to successfully manage and prevent potential anthrax attacks. BioThrax® (Anthrax Vaccine Adsorbed; AVA) is the only licensed anthrax vaccine in the US. Areas covered: Recent licensed improvements to BioThrax vaccine for pre-exposure prophylaxis (PrEP) have included an intramuscular (IM) five-dose schedule (in 2008) and a three-dose IM primary series at 0, 1 and 6 months (in 2012). Post-exposure prophylaxis (PEP) - three doses given subcutaneously (SC) at 0, 2, and 4 weeks - was licensed in 2015. We review the anthrax disease and vaccine literature that supported these licensure efforts. Expert commentary: This PEP licensure is the first time the FDA's Animal Rule has been used to license a vaccine. Additional improvements such as fewer vaccine doses and reduced time to protection are desirable for a PEP vaccine and are being pursued with next generation vaccine candidates.

Prediction of Exposure Level of Energetic Solar Particle Events

NASA Astrophysics Data System (ADS)

Kim, M. H. Y.; Blattnig, S.

2016-12-01

The potential for exposure to large solar particle events (SPEs) with fluxes that extend to high energies is a major concern during interplanetary transfer and extravehicular activities (EVAs) on the lunar and Martian surfaces. Prediction of sporadic occurrence of SPEs is not accurate for near or long-term scales, while the expected frequency of such events is strongly influenced by solar cycle activity. In the development of NASA's operational strategies real-time estimation of exposure to SPEs has been considered so that adequate responses can be applied in a timely manner to reduce exposures to well below the exposure limits. Previously, the organ doses of large historical SPEs had been calculated by using the complete energy spectra of each event and then developing a prediction model for blood-forming organ (BFO) dose based solely on an assumed value of integrated fluence above 30 MeV (Φ30) for an otherwise unspecified future SPE. While BFO dose is determined primarily by solar protons with high energies, it was reasoned that more accurate BFO dose prediction models could be developed using integrated fluence above 60 MeV (Φ60) and above 100 MeV (Φ100) as predictors instead of Φ30. In the current study, re-analysis of major SPEs (in which the proton spectra of the ground level enhancement [GLE] events since 1956 are correctly described by Band functions) has been used in evaluation of exposure levels. More accurate prediction models for BFO dose and NASA effective dose are then developed using integrated fluence above 200 MeV (Φ200), which by far have the most weight in the calculation of doses for deep-seated organs from exposure to extreme SPEs (GLEs or sub-GLEs). The unconditional probability of a BFO dose exceeding a pre-specified BFO dose limit is simultaneously calculated by taking into account the distribution of the predictor (Φ30, Φ60, Φ100, or Φ200) as estimated from historical SPEs. These results can be applied to the development of approaches to improve radiation protection of astronauts and the optimization of mission planning for future space missions.

Dose reconstruction for individuals exposed to ionizing radiation using chromosome painting

NASA Technical Reports Server (NTRS)

Lucas, J. N.; Cox, A. B. (Principal Investigator)

1997-01-01

To be most useful, a biomarker for dose reconstruction should employ an end point that is highly quantitative, stable with time and easily measured. Reciprocal translocations have been shown to be a promising biomarker that is linked to both prior exposure and risk, and they can be measured easily and quantitatively using fluorescence in situ hybridization. In contrast to other biomarkers that are available, the frequency of reciprocal translocations in individuals exposed to whole-body radiation is stable with time after exposure, has rather small interindividual variability and can be measured accurately at low levels of exposure. Results from recent studies demonstrate that measurements of reciprocal translocation frequencies, facilitated by chromosome painting, can be used to reconstruct radiation dose for individuals exposed in the distant past.

Dose reconstruction for individuals exposed to ionizing radiation using chromosome painting.

PubMed

Lucas, J N

1997-11-01

To be most useful, a biomarker for dose reconstruction should employ an end point that is highly quantitative, stable with time and easily measured. Reciprocal translocations have been shown to be a promising biomarker that is linked to both prior exposure and risk, and they can be measured easily and quantitatively using fluorescence in situ hybridization. In contrast to other biomarkers that are available, the frequency of reciprocal translocations in individuals exposed to whole-body radiation is stable with time after exposure, has rather small interindividual variability and can be measured accurately at low levels of exposure. Results from recent studies demonstrate that measurements of reciprocal translocation frequencies, facilitated by chromosome painting, can be used to reconstruct radiation dose for individuals exposed in the distant past.

Deviations from Haber’s Law for Multiple Measures of Acute Lung Injury in Chlorine-Exposed Mice

PubMed Central

Hoyle, Gary W.; Chang, Weiyuan; Chen, Jing; Schlueter, Connie F.; Rando, Roy J.

2010-01-01

Chlorine gas is considered a chemical threat agent that can cause acute lung injury. Studies in the early 20th century on war gases led Haber to postulate that the dose of an inhaled chemical expressed as the product of gas concentration and exposure time leads to a constant toxicological effect (Haber’s Law). In the present work, mice were exposed to a constant dose of chlorine (100 ppm-h) delivered using different combinations of concentration and time (800 ppm/7.5 min, 400 ppm/15 min, 200 ppm/30 min, and 100 ppm/60 min). Significant effects of exposure protocol on survival evaluated 6 h after exposure were observed, ranging from 0% for the 7.5-min exposure to 100% for the 30- and 60-min exposures. Multiple parameters indicative of lung injury were examined to determine if any aspects of lung injury were differentially affected by the exposure protocols. Most parameters (pulmonary edema, neutrophil influx, and levels of protein, immunoglobulin M, and the chemokine KC [Cxcl1] in lavage fluid) indicated that lung injury was most pronounced for the 15-min exposure and least for the 60-min exposure. In contrast, changes in pulmonary function at baseline and in response to inhaled methacholine were similar following the three exposure regimens. The results indicate that the extent of lung injury following chlorine inhalation depends not only on total dose but also on the specifics of exposure concentration and time, and they suggest that evaluation of countermeasures against chlorine-induced lung injury should be performed using multiple types of exposure scenarios. PMID:20819911

Personal exposure to Black Carbon in transport microenvironments

NASA Astrophysics Data System (ADS)

Dons, Evi; Int Panis, Luc; Van Poppel, Martine; Theunis, Jan; Wets, Geert

2012-08-01

We evaluated personal exposure of 62 individuals to the air pollutant Black Carbon, using 13 portable aethalometers while keeping detailed records of their time-activity pattern and whereabouts. Concentrations encountered in transport are studied in depth and related to trip motives. The evaluation comprises more than 1500 trips with different transport modes. Measurements were spread over two seasons. Results show that 6% of the time is spent in transport, but it accounts for 21% of personal exposure to Black Carbon and approximately 30% of inhaled dose. Concentrations in transport were 2-5 times higher compared to concentrations encountered at home. Exposure was highest for car drivers, and car and bus passengers. Concentrations of Black Carbon were only half as much when traveling by bike or on foot; when incorporating breathing rates, dose was found to be twice as high for active modes. Lowest 'in transport' concentrations were measured in trains, but nevertheless these concentrations are double the concentrations measured at home. Two thirds of the trips are car trips, and those trips showed a large spread in concentrations. In-car concentrations are higher during peak hours compared to off-peak, and are elevated on weekdays compared to Saturdays and even more so on Sundays. These findings result in significantly higher exposure during car commute trips (motive 'Work'), and lower concentrations for trips with motive 'Social and leisure'. Because of the many factors influencing exposure in transport, travel time is not a good predictor of integrated personal exposure or inhaled dose.

Effect of dose timing in relation to food intake on systemic exposure to blonanserin.

PubMed

Saruwatari, Junji; Yasui-Furukori, Norio; Inoue, Yoshimasa; Kaneko, Sunao

2010-09-01

Blonanserin is a novel potent dopamine D(2) and serotonin 5-HT(2) antagonist for treating schizophrenia. The aim of this study was to investigate prandial effects on systemic exposure to blonanserin in healthy volunteers, with particular attention paid to the effect of dose timing relative to meal intake. Volunteers received a single 2-mg oral dose of blonanserin under the following conditions: fasting, 30 min before eating a standard meal; or 30 min or 2 or 4 h after eating the meal. Plasma concentrations of blonanserin were measured using validated high-performance liquid chromatography coupled with tandem mass spectrometry. Ratios and 90% confidence intervals of the geometric means compared with the fasting condition indicated that the maximum concentrations of blonanserin (C(max)) significantly increased with dosing 30 min before meal intake, and 30 min and 2 and 4 h after meal intake, yielding by 330%, 239%, 272%, and 138%, respectively. The truncated area under the concentration-time curve (AUC(last)) also increased by 386%, 201%, 256%, and 155%, respectively. There was no difference in values of the time to reach maximum concentration between the fasting and the four fed states. Food intake increased the systemic exposure to blonanserin for all time intervals investigated in this study. The marked effect of food on the bioavailability of blonanserin should be taken into account in its dosing schedules.

Comparison of high MRI T1 signals with manganese concentration in brains of cynomolgus monkeys after 8 months of stainless steel welding-fume exposure.

PubMed

Park, Jung Duck; Chung, Yong Hyun; Kim, Choong Yong; Ha, Chang Soo; Yang, Seoung Oh; Khang, Hyun Soo; Yu, In Kyu; Cheong, Hae Kwan; Lee, Jong Seong; Song, Chang-Woo; Kwon, Il Hoon; Han, Jeong Hee; Sung, Jae Hyuck; Heo, Jeong Doo; Choi, Byung Sun; Im, Ruth; Jeong, Jayoung; Yu, Il Je

2007-09-01

Several pharmacokinetic studies on inhalation exposure to manganese (Mn) have already demonstrated that Mn readily accumulates in the olfactory and brain regions. However, a shortening of the magnetic resonance imaging (MRI) T1 relaxation time or high T1 signal intensity in specific sites of the brain, including the globus pallidus and subcortical frontal white matter, as indicative of tissue manganese accumulation has not yet been clearly established for certain durations of known doses of welding-fume exposure in experimental animals. Accordingly, to investigate the movement of manganese after welding-fume exposure, six cynomolgus monkeys were acclimated and assigned to three dose groups: unexposed, low dose (31 mg/m(3) total suspended particulate [TSP], 0.9 mg/m(3) of Mn), and high dose (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of total suspended particulate. The primates were exposed to manual metal arc stainless steel (MMA-SS) welding fumes for 2 h per day in an inhalation chamber system equipped with an automatic fume generator. Magnetic resonance imaging (MRI) studies were conducted before the initiation of exposure and thereafter every month. The tissue Mn concentrations were then measured after a plateau was reached regarding the shortening of the MRI T1 relaxation time. A dose-dependent increase in the Mn concentration was found in the lungs, while noticeable increases in the Mn concentrations were found in certain tissues, such as the liver, kidneys, and testes. Slight increases in the Mn concentrations were found in the caudate, putamen, frontal lobe, and substantia nigra, while a dose-dependent noticeable increase was only found in the globus pallidus. Therefore, the present results indicated that a shortening of the MRI T1 relaxation time corresponded well with the Mn concentration in the globus pallidus after prolonged welding-fume exposure.

Dermal damage promoted by repeated low-level UV-A1 exposure despite tanning response in human skin.

PubMed

Wang, Frank; Smith, Noah R; Tran, Bao Anh Patrick; Kang, Sewon; Voorhees, John J; Fisher, Gary J

2014-04-01

Solar UV irradiation causes photoaging, characterized by fragmentation and reduced production of type I collagen fibrils that provide strength to skin. Exposure to UV-B irradiation (280-320 nm) causes these changes by inducing matrix metalloproteinase 1 and suppressing type I collagen synthesis. The role of UV-A irradiation (320-400 nm) in promoting similar molecular alterations is less clear yet important to consider because it is 10 to 100 times more abundant in natural sunlight than UV-B irradiation and penetrates deeper into the dermis than UV-B irradiation. Most (approximately 75%) of solar UV-A irradiation is composed of UV-A1 irradiation (340-400 nm), which is also the primary component of tanning beds. To evaluate the effects of low levels of UV-A1 irradiation, as might be encountered in daily life, on expression of matrix metalloproteinase 1 and type I procollagen (the precursor of type I collagen). In vivo biochemical analyses were conducted after UV-A1 irradiation of normal human skin at an academic referral center. Participants included 22 healthy individuals without skin disease. Skin pigmentation was measured by a color meter (chromometer) under the L* variable (luminescence), which ranges from 0 (black) to 100 (white). Gene expression in skin samples was assessed by real-time polymerase chain reaction. Lightly pigmented human skin (L* >65) was exposed up to 4 times (1 exposure/d) to UV-A1 irradiation at a low dose (20 J/cm2), mimicking UV-A levels from strong sun exposure lasting approximately 2 hours. A single exposure to low-dose UV-A1 irradiation darkened skin slightly and did not alter matrix metalloproteinase 1 or type I procollagen gene expression. With repeated low-dose UV-A1 irradiation, skin darkened incrementally with each exposure. Despite this darkening, 2 or more exposures to low-dose UV-A1 irradiation significantly induced matrix metalloproteinase 1 gene expression, which increased progressively with successive exposures. Repeated UV-A1 exposures did not suppress type I procollagen expression. A limited number of low-dose UV-A1 exposures, as commonly experienced in daily life, potentially promotes photoaging by affecting breakdown, rather than synthesis, of collagen. Progressive skin darkening in response to repeated low-dose UV-A1 exposures in lightly pigmented individuals does not prevent UV-A1-induced collagenolytic changes. Therefore, for optimal protection against skin damage, sunscreen formulations should filter all UV wavelengths, including UV-A1 irradiation.

Diagnostic doses and times for Phlebotomus papatasi and Lutzomyia longipalpis sand flies (Diptera: Psychodidae: Phlebotominae) using the CDC bottle bioassay to assess insecticide resistance.

PubMed

Denlinger, David S; Creswell, Joseph A; Anderson, J Laine; Reese, Conor K; Bernhardt, Scott A

2016-04-15

Insecticide resistance to synthetic chemical insecticides is a worldwide concern in phlebotomine sand flies (Diptera: Psychodidae), the vectors of Leishmania spp. parasites. The CDC bottle bioassay assesses resistance by testing populations against verified diagnostic doses and diagnostic times for an insecticide, but the assay has been used limitedly with sand flies. The objective of this study was to determine diagnostic doses and diagnostic times for laboratory Lutzomyia longipalpis (Lutz & Nieva) and Phlebotomus papatasi (Scopoli) to ten insecticides, including pyrethroids, organophosphates, carbamates, and DDT, that are used worldwide to control vectors. Bioassays were conducted in 1,000-ml glass bottles each containing 10-25 sand flies from laboratory colonies of L. longipalpis or P. papatasi. Four pyrethroids, three organophosphates, two carbamates and one organochlorine, were evaluated. A series of concentrations were tested for each insecticide, and four replicates were conducted for each concentration. Diagnostic doses were determined only during the exposure bioassay for the organophosphates and carbamates. For the pyrethroids and DDT, diagnostic doses were determined for both the exposure bioassay and after a 24-hour recovery period. Both species are highly susceptible to the carbamates as their diagnostic doses are under 7.0 μg/ml. Both species are also highly susceptible to DDT during the exposure assay as their diagnostic doses are 7.5 μg/ml, yet their diagnostic doses for the 24-h recovery period are 650.0 μg/ml for Lu. longipalpis and 470.0 μg/ml for P. papatasi. Diagnostic doses and diagnostic times can now be incorporated into vector management programs that use the CDC bottle bioassay to assess insecticide resistance in field populations of Lu. longipalpis and P. papatasi. These findings provide initial starting points for determining diagnostic doses and diagnostic times for other sand fly vector species and wild populations using the CDC bottle bioassay.

Metabolic changes in serum steroids induced by total-body irradiation of female C57B/6 mice.

PubMed

Moon, Ju-Yeon; Shin, Hee-June; Son, Hyun-Hwa; Lee, Jeongae; Jung, Uhee; Jo, Sung-Kee; Kim, Hyun Sik; Kwon, Kyung-Hoon; Park, Kyu Hwan; Chung, Bong Chul; Choi, Man Ho

2014-05-01

The short- and long-term effects of a single exposure to gamma radiation on steroid metabolism were investigated in mice. Gas chromatography-mass spectrometry was used to generate quantitative profiles of serum steroid levels in mice that had undergone total-body irradiation (TBI) at doses of 0Gy, 1Gy, and 4Gy. Following TBI, serum samples were collected at the pre-dose time point and 1, 3, 6, and 9 months after TBI. Serum levels of progestins, progesterone, 5β-DHP, 5α-DHP, and 20α-DHP showed a significant down-regulation following short-term exposure to 4Gy, with the exception of 20α-DHP, which was significantly decreased at each of the time points measured. The corticosteroids 5α-THDOC and 5α-DHB were significantly elevated at each of the time points measured after exposure to either 1 or 4Gy. Among the sterols, 24S-OH-cholestoerol showed a dose-related elevation after irradiation that reached significance in the high dose group at the 6- and 9-month time points. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparative MicroRNA Expression Patterns in Fibroblasts after Low and High Doses of Low-LET Radiation Exposure

NASA Technical Reports Server (NTRS)

Maes, Olivier C.; Xu, Suying; Hada, Megumi; Wu, Honglu; Wang, Eugenia

2007-01-01

Exposure to ionizing radiation causes DNA damage to cells, and provokes a plethora of cellular responses controlled by unique gene-directed signaling pathways. MicroRNAs (miRNAs) are small (22-nucleotide), non-coding RNAs which functionally silence gene expression by either degrading the messages or inhibiting translation. Here we investigate radiation-dependent changes in these negative regulators by comparing the expression patterns of all 462 known human miRNAs in fibroblasts, after exposure to low (0.1 Gy) or high (2 Gy) doses of X-rays at 30 min, 2, 6 and 24 hrs post-treatment. The expression patterns of microRNAs after low and high doses of radiation show a similar qualitative down-regulation trend at early (0.5 hr) and late (24 hr) time points, with a quantitatively steeper slope following the 2 Gy exposures. Interestingly, an interruption of this downward trend is observed after the 2 Gy exposure, i.e. a significant up-regulation of microRNAs at 2 hrs, then reverting to the downward trend by 6 hrs; this interruption at the intermediate time point was not observed with the 0.1 Gy exposure. At the early time point (0.5 hr), candidate gene targets of selected down-regulated microRNAs, common to both 0.1 and 2 Gy exposures, were those functioning in chromatin remodeling. Candidate target genes of unique up-regulated microRNAs seen at a 2 hr intermediate time point, after the 2 Gy exposure only, are those involved in cell death signaling. Finally, putative target genes of down-regulated microRNAs seen at the late (24 hr) time point after either doses of radiation are those involved in the up-regulation of DNA repair, cell signaling and homeostasis. Thus we hypothesize that after radiation exposure, microRNAs acting as hub negative regulators for unique signaling pathways needed to be down-regulated so as to de-repress their target genes for the proper cellular responses, including DNA repair and cell maintenance. The unique microRNAs up-regulated at 2 hr after 2 Gy suggest the cellular response to functionally suppress the apoptotic death signaling reflex after exposure to high dose radiation. Further analyses with transcriptome and global proteomic profiling will validate the reciprocal expression of signature microRNAs selected in our radiation-exposed cells, and their candidate target gene families, and test our hypothesis that unique radiation-specific microRNAs are keys in governing signaling responses for damage control of this environmental hazard.

Effective biological dose from occupational exposure during nanoparticle synthesis

NASA Astrophysics Data System (ADS)

Demou, Evangelia; Tran, Lang; Housiadas, Christos

2009-02-01

Nanomaterial and nanotechnology safety require the characterization of occupational exposure levels for completing a risk assessment. However, equally important is the estimation of the effective internal dose via lung deposition, transport and clearance mechanisms. An integrated source-to-biological dose assessment study is presented using real monitoring data collected during nanoparticle synthesis. Experimental monitoring data of airborne exposure levels during nanoparticle synthesis of CaSO4 and BiPO4 nanoparticles in a research laboratory is coupled with a human lung transport and deposition model, which solves in an Eulerian framework the general dynamic equation for polydisperse aerosols using particle specific physical-chemical properties. Subsequently, the lung deposition model is coupled with a mathematical particle clearance model providing the effective biological dose as well as the time course of the biological dose build-up after exposure. The results for the example of BiPO4 demonstrate that even short exposures throughout the day can lead to particle doses of 1.10·E+08#/(kg-bw·8h-shift), with the majority accumulating in the pulmonary region. Clearance of particles is slow and is not completed within a working shift following a 1 hour exposure. It mostly occurs via macrophage activity in the alveolar region, with small amounts transported to the interstitium and less to the lymph nodes.

Uncovering the proteome response of murine neuroblastoma cells against low-dose exposure to saxitoxin.

PubMed

Chen, Xiao; Sun, Ye; Huang, Haiyan; Liu, Wei; Hu, Panpan; Huang, Xinfeng; Zou, Fei; Liu, Jianjun

2018-06-01

The potent neurotoxin saxitoxin produced by both marine and freshwater phytoplankton causes paralytic shellfish poisoning syndrome. The toxicity and mode of action of the acute exposure of high-dose saxitoxin have been intensively studied for decades; however, the potential risk of exposure of low-dose saxitoxin remained to be uncovered. Here we present a proteomics study of murine neuroblastoma N2A cell with low-dose saxitoxin exposure (1 nM and 10 nM, 24-h intoxication). Differential proteins were profiled by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). A total of 9 proteins, including 14-3-3 beta (1433B), alpha enolase (ENO1) and cofilin 2 (CFL2), were altered by the low-dose saxitoxin exposure. We further validated the expressions of 1433B, ENO1 and CFL2 by Western blot analysis and the enzyme-linked immunosorbent assay. These 9 proteins involve cell apoptotic pathways, cell skeleton maintenance, membrane potentials and mitochondrial functions. Modulation of these 9 proteins by low-dose saxitoxin exposure could correlate to the reports on genotoxicity and neurotoxicity induced by saxitoxin. This study also suggested other potential risks of saxitoxin.

Fluoroscopic exposure in modern spinal surgery.

PubMed

Fransen, Patrick

2011-06-01

The widespread use of minimally invasive and other spinal procedures raises concern about the peroperative radiation exposure to surgeon and patient. The authors noted the fluoroscopy time and the radiation dose, as read from the image amplifier, in 95 spinal procedures. The results of this prospective study varied widely between different operations. Percutaneous surgery was associated with more exposure than open surgery. For instance, the average radiation dose per pedicle screw was 3.2 times higher with percutaneous insertion than with an open approach. Therefore, efforts to reduce fluoroscopy time and radiation exposure should be made when using minimally invasive percutaneous surgical techniques. Preventive measures for the surgeon, such as lead aprons and gloves, thyroid shields, radioprotective glasses and staying away from the beam are recommended. Still from the surgeon's view-point, source inferior positioning of the image amplifier is indicated for the AP view, as well as monitoring of the radiation exposure. Finally, the difference in fluoroscopy time and radiation exposure between surgeons for the same procedure stresses the fact that peroperative radiation may be reduced by simple awareness and by training.

GDF-15 gene expression alterations in human lymphoblastoid cells and peripheral blood lymphocytes following exposure to ionizing radiation

PubMed Central

Li, Shuang; Zhang, Qing-Zhao; Zhang, De-Qin; Feng, Jiang-Bin; Luo, Qun; Lu, Xue; Wang, Xin-Ru; Li, Kun-Peng; Chen, De-Qing; Mu, Xiao-Feng; Gao, Ling; Liu, Qing-Jie

2017-01-01

The identification of rapid, sensitive and high-throughput biomarkers is imperative in order to identify individuals harmed by radiation accidents, and accurately evaluate the absorbed doses of radiation. DNA microarrays have previously been used to evaluate the alterations in growth/differentiation factor 15 (GDF15) gene expression in AHH-1 human lymphoblastoid cells, following exposure to γ-rays. The present study aimed to characterize the relationship between the dose of ionizing radiation and the produced effects in GDF-15 gene expression in AHH-1 cells and human peripheral blood lymphocytes (HPBLs). GDF-15 mRNA and protein expression levels following exposure to γ-rays and neutron radiation were assessed by reverse transcription-quantitative polymerase chain reaction and western blot analysis in AHH-1 cells. In addition, alterations in GDF-15 gene expression in HPBLs following ex vivo irradiation were evaluated. The present results demonstrated that GDF-15 mRNA and protein expression levels in AHH-1 cells were significantly upregulated following exposure to γ-ray doses ranging between 1 and 10 Gy, regardless of the dose rate. A total of 48 h following exposure to neutron radiation, a dose-response relationship was identified in AHH-1 cells at γ-ray doses between 0.4 and 1.6 Gy. GDF-15 mRNA levels in HPBLs were significantly upregulated following exposure to γ-ray doses between 1 and 8 Gy, within 4–48 h following irradiation. These results suggested that significant time- and dose-dependent alterations in GDF-15 mRNA and protein expression occur in AHH-1 cells and HPBLs in the early phases following exposure to ionizing radiation. In conclusion, alterations in GDF-15 gene expression may have potential as a biomarker to evaluate radiation exposure. PMID:28440431

The influence of lifestyle on airborne particle surface area doses received by different Western populations.

PubMed

Pacitto, A; Stabile, L; Moreno, T; Kumar, P; Wierzbicka, A; Morawska, L; Buonanno, G

2018-01-01

In the present study, the daily dose in terms of particle surface area received by citizens living in five cities in Western countries, characterized by different lifestyle, culture, climate and built-up environment, was evaluated and compared. For this purpose, the exposure to sub-micron particle concentration levels of the population living in Barcelona (Spain), Cassino (Italy), Guilford (United Kingdom), Lund (Sweden), and Brisbane (Australia) was measured through a direct exposure assessment approach. In particular, measurements of the exposure at a personal scale were performed by volunteers (15 per each population) that used a personal particle counter for different days in order to obtain exposure data in microenvironments/activities they resided/performed. Non-smoking volunteers performing non-industrial jobs were considered in the study. Particle concentration data allowed obtaining the exposure of the population living in each city. Such data were combined in a Monte Carlo method with the time activity pattern data characteristics of each population and inhalation rate to obtain the most probable daily dose in term of particle surface area as a function of the population gender, age, and nationality. The highest daily dose was estimated for citizens living in Cassino and Guilford (>1000 mm 2 ), whereas the lowest value was recognized for Lund citizens (around 100 mm 2 ). Indoor air quality, and in particular cooking and eating activities, was recognized as the main influencing factor in terms of exposure (and thus dose) of the population: then confirming that lifestyle (e.g. time spent in cooking activities) strongly affect the daily dose of the population. On the contrary, a minor or negligible contribution of the outdoor microenvironments was documented. Copyright © 2017 Elsevier Ltd. All rights reserved.

High-resolution short-exposure small-animal laboratory x-ray phase-contrast tomography

NASA Astrophysics Data System (ADS)

Larsson, Daniel H.; Vågberg, William; Yaroshenko, Andre; Yildirim, Ali Önder; Hertz, Hans M.

2016-12-01

X-ray computed tomography of small animals and their organs is an essential tool in basic and preclinical biomedical research. In both phase-contrast and absorption tomography high spatial resolution and short exposure times are of key importance. However, the observable spatial resolutions and achievable exposure times are presently limited by system parameters rather than more fundamental constraints like, e.g., dose. Here we demonstrate laboratory tomography with few-ten μm spatial resolution and few-minute exposure time at an acceptable dose for small-animal imaging, both with absorption contrast and phase contrast. The method relies on a magnifying imaging scheme in combination with a high-power small-spot liquid-metal-jet electron-impact source. The tomographic imaging is demonstrated on intact mouse, phantoms and excised lungs, both healthy and with pulmonary emphysema.

Thyroid Cancer Following Childhood Low-Dose Radiation Exposure: A Pooled Analysis of Nine Cohorts.

PubMed

Lubin, Jay H; Adams, M Jacob; Shore, Roy; Holmberg, Erik; Schneider, Arthur B; Hawkins, Michael M; Robison, Leslie L; Inskip, Peter D; Lundell, Marie; Johansson, Robert; Kleinerman, Ruth A; de Vathaire, Florent; Damber, Lena; Sadetzki, Siegal; Tucker, Margaret; Sakata, Ritsu; Veiga, Lene H S

2017-07-01

The increased use of diagnostic and therapeutic procedures that involve radiation raises concerns about radiation effects, particularly in children and the radiosensitive thyroid gland. Evaluation of relative risk (RR) trends for thyroid radiation doses <0.2 gray (Gy); evidence of a threshold dose; and possible modifiers of the dose-response, e.g., sex, age at exposure, time since exposure. Pooled data from nine cohort studies of childhood external radiation exposure and thyroid cancer with individualized dose estimates, ≥1000 irradiated subjects or ≥10 thyroid cancer cases, with data limited to individuals receiving doses <0.2 Gy. Cohorts included the following: childhood cancer survivors (n = 2); children treated for benign diseases (n = 6); and children who survived the atomic bombings in Japan (n = 1). There were 252 cases and 2,588,559 person-years in irradiated individuals and 142 cases and 1,865,957 person-years in nonirradiated individuals. There were no interventions. Incident thyroid cancers. For both <0.2 and <0.1 Gy, RRs increased with thyroid dose (P < 0.01), without significant departure from linearity (P = 0.77 and P = 0.66, respectively). Estimates of threshold dose ranged from 0.0 to 0.03 Gy, with an upper 95% confidence bound of 0.04 Gy. The increasing dose-response trend persisted >45 years after exposure, was greater at younger age at exposure and younger attained age, and was similar by sex and number of treatments. Our analyses reaffirmed linearity of the dose response as the most plausible relationship for "as low as reasonably achievable" assessments for pediatric low-dose radiation-associated thyroid cancer risk. Copyright © 2017 Endocrine Society

Identification of Differential Gene Expression Patterns after Acute Exposure to High and Low Doses of Low-LET Ionizing Radiation in a Reconstituted Human Skin Tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tilton, Susan C.; Markillie, Lye Meng; Hays, Spencer

Our goal here was to identify dose and temporal dependent radiation responses in a complex tissue, reconstituted human skin. Direct sequencing of RNA (RNA-seq) was used to quantify altered transcripts following exposure to 0.1, 2 and 10 Gy of ionizing radiation at 3 and 8 hours. These doses include a low dose in the range of some medical diagnostic procedures (0.1 Gy), a dose typically received during radiotherapy (2.0 Gy) and a lethal dose (10 Gy). These doses could be received after an intentional or accidental radiation exposure and biomarkers are needed to rapidly and accurately triage exposed individuals. Amore » total of 1701 genes were deemed to be significantly affected by high dose radiation exposure with the majority of genes affected at 10 Gy. A group of 29 genes including GDF15, BBC3, PPM1D, FDXR, GADD45A, MDM2, CDKN1A, TP53INP1, CYCSP27, SESN1, SESN2, PCNA, and AEN were similarly altered at both 2 and 10 Gy, but not 0.1 Gy, at multiple time points. A much larger group of up regulated genes, including those involved in inflammatory responses, was significantly altered only after a 10 Gy exposure. At high doses, down regulated genes were associated with cell cycle regulation and exhibited an apparent linear response between 2 and 10 Gy. While only a handful of genes were significantly affected by 0.1 Gy exposure using stringent statistical filters, groups of related genes regulating cell cycle progression and inflammatory responses consistently exhibited opposite trends in their regulation compared to the high dose exposures. Differential regulation of PLK1 signaling at low and high doses was confirmed using qRT-PCR. These results indicate that some alterations in gene expression are qualitatively different at low and high doses of radiation in this model system.« less

Optimization of dual-energy subtraction chest radiography by use of a direct-conversion flat-panel detector system.

PubMed

Fukao, Mari; Kawamoto, Kiyosumi; Matsuzawa, Hiroaki; Honda, Osamu; Iwaki, Takeshi; Doi, Tsukasa

2015-01-01

We aimed to optimize the exposure conditions in the acquisition of soft-tissue images using dual-energy subtraction chest radiography with a direct-conversion flat-panel detector system. Two separate chest images were acquired at high- and low-energy exposures with standard or thick chest phantoms. The high-energy exposure was fixed at 120 kVp with the use of an auto-exposure control technique. For the low-energy exposure, the tube voltages and entrance surface doses ranged 40-80 kVp and 20-100 % of the dose required for high-energy exposure, respectively. Further, a repetitive processing algorithm was used for reduction of the image noise generated by the subtraction process. Seven radiology technicians ranked soft-tissue images, and these results were analyzed using the normalized-rank method. Images acquired at 60 kVp were of acceptable quality regardless of the entrance surface dose and phantom size. Using a repetitive processing algorithm, the minimum acceptable doses were reduced from 75 to 40 % for the standard phantom and to 50 % for the thick phantom. We determined that the optimum low-energy exposure was 60 kVp at 50 % of the dose required for the high-energy exposure. This allowed the simultaneous acquisition of standard radiographs and soft-tissue images at 1.5 times the dose required for a standard radiograph, which is significantly lower than the values reported previously.

Assessment of occupational cosmic radiation exposure of flight attendants using questionnaire data.

PubMed

Anderson, Jeri L; Waters, Martha A; Hein, Misty J; Schubauer-Berigan, Mary K; Pinkerton, Lynne E

2011-11-01

Female flight attendants may have a higher risk of breast and other cancers than the general population because of routine exposure to cosmic radiation. As part of a forthcoming study of breast and other cancer incidence, occupational cosmic radiation exposure of a cohort of female flight attendants was estimated. Questionnaire data were collected from living female cohort members who were formerly employed as flight attendants with Pan American World Airways. These data included airline at which the flight attendant was employed, assigned domicile, start and end dates for employment at domicile, and number of block hours and commuter segments flown per month. Questionnaire respondents were assigned daily absorbed and effective doses using a time-weighted dose rate specific to the domicile and/or work history era combined with self-reported work history information. Completed work history questionnaires were received from 5898 living cohort members. Mean employment time as a flight attendant was 7.4 yr at Pan Am and 12 yr in total. Estimated mean annual effective dose from all sources of occupational cosmic radiation exposure was 2.5 +/- 1.0 mSv, with a mean career dose of 30 mSv. Annual effective doses were similar to doses assessed for other flight attendant cohorts; however, questionnaire-based cumulative doses assessed in this study were on average higher than those assessed for other flight attendant cohorts using company-based records. The difference is attributed to the inclusion of dose from work at other airlines and commuter flights, which was made possible by using questionnaire data.

Radiation-associated circulatory disease mortality in a pooled analysis of 77,275 patients from the Massachusetts and Canadian tuberculosis fluoroscopy cohorts.

PubMed

Tran, Van; Zablotska, Lydia B; Brenner, Alina V; Little, Mark P

2017-03-13

High-dose ionising radiation is associated with circulatory disease. Risks associated with lower-dose (<0.5 Gy) exposures remain unclear, with little information on risk modification by age at exposure, years since exposure or dose-rate. Tuberculosis patients in Canada and Massachusetts received multiple diagnostic x-ray fluoroscopic exposures, over a wide range of ages, many at doses <0.5 Gy. We evaluated risks of circulatory-disease mortality associated with <0.5 Gy radiation exposure in a pooled cohort of 63,707 patients in Canada and 13,568 patients in Massachusetts. Under 0.5 Gy there are increasing trends for all circulatory disease (n = 10,209; excess relative risk/Gy = 0.246; 95% CI 0.036, 0.469; p = 0.021) and for ischaemic heart disease (n = 6410; excess relative risk/Gy = 0.267; 95% CI 0.003, 0.552; p = 0.048). All circulatory-disease and ischaemic-heart-disease risk reduces with increasing time since exposure (p < 0.005). Over the entire dose range, there are negative mortality dose trends for all circulatory disease (p = 0.014) and ischaemic heart disease (p = 0.003), possibly due to competing causes of death over this dose interval.These results confirm and extend earlier findings and strengthen the evidence for circulatory-disease mortality radiation risk at doses <0.5 Gy. The limited information on well-known lifestyle/medical risk factors for circulatory disease implies that confounding of the dose trend cannot be entirely excluded.

ESTIMATION OF INTERNAL EXPOSURE TO URANIUM WITH UNCERTAINTY FROM URINALYSIS DATA USING THE InDEP COMPUTER CODE

PubMed Central

Anderson, Jeri L.; Apostoaei, A. Iulian; Thomas, Brian A.

2015-01-01

The National Institute for Occupational Safety and Health (NIOSH) is currently studying mortality in a cohort of 6409 workers at a former uranium processing facility. As part of this study, over 220 000 urine samples were used to reconstruct organ doses due to internal exposure to uranium. Most of the available computational programs designed for analysis of bioassay data handle a single case at a time, and thus require a significant outlay of time and resources for the exposure assessment of a large cohort. NIOSH is currently supporting the development of a computer program, InDEP (Internal Dose Evaluation Program), to facilitate internal radiation exposure assessment as part of epidemiological studies of both uranium- and plutonium-exposed cohorts. A novel feature of InDEP is its batch processing capability which allows for the evaluation of multiple study subjects simultaneously. InDEP analyses bioassay data and derives intakes and organ doses with uncertainty estimates using least-squares regression techniques or using the Bayes’ Theorem as applied to internal dosimetry (Bayesian method). This paper describes the application of the current version of InDEP to formulate assumptions about the characteristics of exposure at the study facility that were used in a detailed retrospective intake and organ dose assessment of the cohort. PMID:22683620

Postexposure bake characteristics of a chemically amplified deep-ultraviolet resist

NASA Astrophysics Data System (ADS)

Sturtevant, John L.; Holmes, Steven J.; Rabidoux, Paul A.

1992-06-01

In the processing of chemically amplified resist systems, two `dose' parameters must be considered. The exposure dose dictates the amount of photoacid generated, and the thermal dose that is administered during the post-exposure bake (PEB) governs the extent to which the resin is chemically transformed by the acid. An Arrhenius relationship exists between these two dose variables, and the magnitude of the effective activation energy determines the degree of PEB temperature control required for a particular linewidth budget. PEB characteristics are presented for a chemically amplified positive-tone DUV resist used by IBM in the manufacture of 0.5 micrometers 16 Mb DRAMs. The effect of PEB temperature and time on resist sensitivity, contrast, resolution, and process latitude is presented. The influence of exposure and thermal dose on the chemical contamination effect is also discussed.

Action spectrum for phototherapy of psoriasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parrish, J.A.; Jaenicke, K.F.

1981-05-01

Using a monochromator the action spectrum for ultraviolet phototherapy of psoriasis was determined for radiation between 254 and 313 nm and compared to the action spectrum for erythema of uninvolved adjacent skin. Daily exposures of different doses of 254, 280, 290, 296, 300, 304 and 313 nm radiation were observed. Wavelengths of 254, 280, 290 nm were erythemogenic but not therapeutic even at 10 to 50 times the minimal erythema dose. At the other wavelengths studied, the 2 action spectra were similar. In general, fixed daily doses cleared at lower cumulative dose than did incrementally increased daily doses. The smallmore » number of suberythemogenic exposure doses required suggests that monochromatic radiation may have advantages over broadband sources.« less

Micro RNA responses to chronic or acute exposures to low dose ionizing radiation

PubMed Central

Chaudhry, M. Ahmad; Omaruddin, Romaica A.; Kreger, Bridget; de Toledo, Sonia M.; Azzam, Edouard I.

2014-01-01

Human health risks of exposure to low dose ionizing radiation remain ambiguous and are the subject of intense debate. A wide variety of biological effects are induced after cellular exposure to ionizing radiation, but the underlying molecular mechanism(s) remain to be completely understood. We hypothesized that low dose c-radiation-induced effects are controlled by the modulation of micro RNA (miRNA) that participate in the control of gene expression at the posttranscriptional level and are involved in many cellular processes. We monitored the expression of several miRNA in human cells exposed to acute or chronic low doses of 10 cGy or a moderate dose of 400 cGy of 137Cs γ-rays. Dose, dose rate and time dependent differences in the relative expression of several miRNA were investigated. The expression patterns of many miRNA differed after exposure to either chronic or acute 10 cGy. The expression of miRNA let-7e, a negative regulator of RAS oncogene, and the c-MYC miRNA cluster were upregulated after 10 cGy chronic dose but were downregulated after 3 h of acute 10 cGy. The miR-21 was upregulated in chronic or acute low dose and moderate dose treated cells and its target genes hPDCD4, hPTEN, hSPRY2, and hTPM1 were found to be downregulated. These findings provide evidence that low dose and dose rate c-irradiation dictate the modulation of miRNA, which can result in a differential cellular response than occurs at high doses. This information will contribute to understanding the risks to human health after exposure to low dose radiation. PMID:22367372

Pergolide: multiple-dose pharmacokinetics in patients with mild to moderate Parkinson disease.

PubMed

Thalamas, Claire; Rajman, Iris; Kulisevsky, Jaime; Lledó, Alberto; Mackie, Alison E; Blin, Olivier; Gillespie, Todd A; Seger, Mary; Rascol, Olivier

2005-01-01

The primary objective of this study was to describe the pharmacokinetics of oral pergolide in patients with mild to moderate Parkinson disease using a new high-performance liquid chromatography-tandem mass spectrometry assay. A secondary objective was to investigate the relationship between plasma concentrations and efficacy. Fourteen patients with a diagnosis of Parkinson disease completed this multicenter, open-label, dose-escalating study. Pergolide was administered for 58 days, using increasing daily doses from 0.05 mg daily up to 1 mg three times daily and then tapering the dose. The steady-state pharmacokinetic profile and motor score were determined at dose levels of 0.25, 0.5, and 1 mg three times a day and during elimination after the last dose. Pergolide was absorbed with a median time to maximum concentration of 2 to 3 hours across the dose range. Systemic exposure appeared to increase proportionally with dose over the range of 0.25 to 1 mg three times daily within a patient, but there was a large variability in exposures between patients (interpatient coefficients of variation were 56.4% for the area under the curve). Pergolide was widely distributed (volume of distribution, approximately 14,000 L) and was eliminated with a mean half-life of 21 hours. Motor scores improved as both peak plasma pergolide concentrations and exposure increased. No unexpected safety concerns were identified. Pergolide is absorbed relatively quickly into the systemic circulation, has a large apparent volume of distribution, and has a relatively long half-life (mean, 21 hours). This prolonged half-life is of particular interest, given the current hypothesis that more continuous dopaminergic receptor stimulation may reduce motor complications in patients with Parkinson disease.

INTERNAL DOSE AND RESPONSE IN REAL-TIME.

EPA Science Inventory

Abstract: Rapid temporal fluctuations in exposure may occur in a number of situations such as accidents or other unexpected acute releases of airborne substances. Often risk assessments overlook temporal exposure patterns under simplifying assumptions such as the use of time-wei...

Doses from external irradiation to Marshall Islanders from Bikini and Enewetak nuclear weapons tests.

PubMed

Bouville, André; Beck, Harold L; Simon, Steven L

2010-08-01

Annual doses from external irradiation resulting from exposure to fallout from the 65 atmospheric nuclear weapons tests conducted in the Marshall Islands at Bikini and Enewetak between 1946 and 1958 have been estimated for the first time for Marshallese living on all inhabited atolls. All tests that deposited fallout on any of the 23 inhabited atolls or separate reef islands have been considered. The methodology used to estimate the radiation doses at the inhabited atolls is based on test- and location-specific radiation survey data, deposition density estimates of 137Cs, and fallout times-of-arrival provided in a companion paper (Beck et al.), combined with information on the radionuclide composition of the fallout at various times after each test. These estimates of doses from external irradiation have been combined with corresponding estimates of doses from internal irradiation, given in a companion paper (Simon et al.), to assess the cancer risks among the Marshallese population (Land et al.) resulting from exposure to radiation from the nuclear weapons tests.

Dose-dependent fluoxetine effects on boldness in male Siamese fighting fish.

PubMed

Dzieweczynski, Teresa L; Campbell, Brennah A; Kane, Jessica L

2016-03-01

As the use of pharmaceuticals and personal care products (PPCPs) continues to rise, these compounds enter the environment in increasing frequency. One such PPCP, fluoxetine, has been found in detectable amounts in aquatic ecosystems worldwide, where it may interfere with the behavior of exposed organisms. Fluoxetine exposure has been found to influence boldness and exploration in a range of fish species; however, how it might alter behavior in multiple contexts or over time is rarely examined. To this end, the effects of fluoxetine on boldness over time were studied in male Siamese fighting fish. Three different groups of males (0, 0.5 and 5 µg l(-1) fluoxetine) were tested in multiple boldness assays (empty tank, novel environment and shoal) once a week for 3 weeks to collect baseline measures and then at three different time points post-exposure. The effects of these varying exposure amounts on behavior were then examined for overall response, consistency and across-context correlations. Unexposed males were bolder in all contexts, were more consistent within a context, and had stronger between-context correlations than exposed males. Fluoxetine had dose-dependent effects on behavior, as males that received the higher dose exhibited greater behavioral effects. This study stresses the potential fitness consequences of fluoxetine exposure and suggests that examining behavioral effects of PPCPs under different dosing regimens and in multiple contexts is important to gain an increased understanding of how exposure affects behavior. © 2016. Published by The Company of Biologists Ltd.

A MODEL TO EVALUATE PAST EXPOSURE TO 2,3,7,8 ...

EPA Pesticide Factsheets

Data from several studies suggest that concentrations of dioxins rose in the environment from the 1930s to about the 1960s/70s and have been declining over the last decade or two. The most direct evidence of this trend comes from lake core sediments, which can be used to estimate past atmospheric depositions of dioxins. The primary source of human exposure to dioxins is through the food supply. The pathway relating atmospheric depositions to concentrations in food is quite complex, and accordingly, it is not known to what extent the trend in human exposure mirrors the trend in atmospheric depositions. This paper describes an attempt to statistically reconstruct the pattern of past human exposure to the most toxic dioxin congener, 2,3,7,8-TCDD (abbreviated TCDD), through use of a simple pharmacokinetic (PK) model which included a time-varying TCDD exposure dose. This PK model was fit to TCDD body burden data (i.e., TCDD concentrations in lipid) from five U.S. studies dating from 1972 to 1987 and covering a wide age range. A Bayesian statistical approach was used to fit TCDD exposure; model parameters other than exposure were all previously known or estimated from other data sources. The primary results of the analysis are as follows: 1.) use of a time-varying exposure dose provided a far better fit to the TCDD body burden data than did using a dose that was constant over time; this is strong evidence that exposure to TCDD has, in fact, varied during the

Survey of Occupational Noise Exposure in CF Personnel in Selected High-Risk Trades

DTIC Science & Technology

2003-11-01

peak, maximum level , minimum level , average sound level , time weighted average, dose, projected 8-hour dose, and upper limit time were measured for...10 4.4.2 Maximum Sound Level ...11 4.4.3 Minimum Sound Level

Breast cancer risk from low-dose exposures to ionizing radiation: results of parallel analysis of three exposed populations of women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Land, C.E.; Boice, J.D. Jr.; Shore, R.E.

1980-08-01

Breast cancer incidence data were analyzed from three populations of women exposed to ionizing radiation: survivors of the Hiroshima and Nagasaki atomic bombs, patients in Massachusetts tuberculosis sanitoria who were exposed to multiple chest fluoroscopies, and patients treated by X-rays for acute postpartum mastitis in Rochester, New York. Parallel analyses by radiation dose, age at exposure, and time after exposure suggested that risk of radiation-induced cancer increased approximately linearly with increasing dose and was heavily dependent on age at exposure; however, the risk was otherwise remarkably similar among the three populations, at least for ages 10 to 40 years atmore » exposure, and followed the same temporal pattern of occurrence as did breast cancer incidence in nonexposed women of similar ages.« less

[Evaluation of an Experimental Production Wireless Dose Monitoring System for Radiation Exposure Management of Medical Staff].

PubMed

Fujibuchi, Toshioh; Murazaki, Hiroo; Kuramoto, Taku; Umedzu, Yoshiyuki; Ishigaki, Yung

2015-08-01

Because of the more advanced and more complex procedures in interventional radiology, longer treatment times have become necessary. Therefore, it is important to determine the exposure doses received by operators and patients. The aim of our study was to evaluate an experimental production wireless dose monitoring system for pulse radiation in diagnostic X-ray. The energy, dose rate, and pulse fluoroscopy dependence were evaluated as the basic characteristics of this system for diagnostic X-ray using a fully digital fluoroscopy system. The error of 1 cm dose equivalent rate was less than 15% from 35.1 keV to 43.2 keV with energy correction using metal filter. It was possible to accurately measure the dose rate dependence of this system, which was highly linear until 100 μSv/h. This system showed a constant response to the pulse fluoroscopy. This system will become useful wireless dosimeter for the individual exposure management by improving the high dose rate and the energy characteristics.

Joint minimization of uplink and downlink whole-body exposure dose in indoor wireless networks.

PubMed

Plets, D; Joseph, W; Vanhecke, K; Vermeeren, G; Wiart, J; Aerts, S; Varsier, N; Martens, L

2015-01-01

The total whole-body exposure dose in indoor wireless networks is minimized. For the first time, indoor wireless networks are designed and simulated for a minimal exposure dose, where both uplink and downlink are considered. The impact of the minimization is numerically assessed for four scenarios: two WiFi configurations with different throughputs, a Universal Mobile Telecommunications System (UMTS) configuration for phone call traffic, and a Long-Term Evolution (LTE) configuration with a high data rate. Also, the influence of the uplink usage on the total absorbed dose is characterized. Downlink dose reductions of at least 75% are observed when adding more base stations with a lower transmit power. Total dose reductions decrease with increasing uplink usage for WiFi due to the lack of uplink power control but are maintained for LTE and UMTS. Uplink doses become dominant over downlink doses for usages of only a few seconds for WiFi. For UMTS and LTE, an almost continuous uplink usage is required to have a significant effect on the total dose, thanks to the power control mechanism.

Joint Minimization of Uplink and Downlink Whole-Body Exposure Dose in Indoor Wireless Networks

PubMed Central

Plets, D.; Joseph, W.; Vanhecke, K.; Vermeeren, G.; Wiart, J.; Aerts, S.; Varsier, N.; Martens, L.

2015-01-01

The total whole-body exposure dose in indoor wireless networks is minimized. For the first time, indoor wireless networks are designed and simulated for a minimal exposure dose, where both uplink and downlink are considered. The impact of the minimization is numerically assessed for four scenarios: two WiFi configurations with different throughputs, a Universal Mobile Telecommunications System (UMTS) configuration for phone call traffic, and a Long-Term Evolution (LTE) configuration with a high data rate. Also, the influence of the uplink usage on the total absorbed dose is characterized. Downlink dose reductions of at least 75% are observed when adding more base stations with a lower transmit power. Total dose reductions decrease with increasing uplink usage for WiFi due to the lack of uplink power control but are maintained for LTE and UMTS. Uplink doses become dominant over downlink doses for usages of only a few seconds for WiFi. For UMTS and LTE, an almost continuous uplink usage is required to have a significant effect on the total dose, thanks to the power control mechanism. PMID:25793213

Health effects in women exposed to low levels of ionizing radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fabrikant, J.I.

1982-06-01

There are three delayed health effects of radiation which appear at the present time to have importance to women in radiation protection. These are: (1) the probability of cancer-induction at low doses and low-dose rates; (2) the consideration of those cancers in women, notably the breast and the thyroid, attributable to radiation exposure; and (3) the probability of induction of developmental abnormalities in the newborn following low-dose exposure in utero. The bases for the concern over these effects are discussed. (ACR)

Elimination of water pathogens with solar radiation using an automated sequential batch CPC reactor.

PubMed

Polo-López, M I; Fernández-Ibáñez, P; Ubomba-Jaswa, E; Navntoft, C; García-Fernández, I; Dunlop, P S M; Schmid, M; Byrne, J A; McGuigan, K G

2011-11-30

Solar disinfection (SODIS) of water is a well-known, effective treatment process which is practiced at household level in many developing countries. However, this process is limited by the small volume treated and there is no indication of treatment efficacy for the user. Low cost glass tube reactors, together with compound parabolic collector (CPC) technology, have been shown to significantly increase the efficiency of solar disinfection. However, these reactors still require user input to control each batch SODIS process and there is no feedback that the process is complete. Automatic operation of the batch SODIS process, controlled by UVA-radiation sensors, can provide information on the status of the process, can ensure the required UVA dose to achieve complete disinfection is received and reduces user work-load through automatic sequential batch processing. In this work, an enhanced CPC photo-reactor with a concentration factor of 1.89 was developed. The apparatus was automated to achieve exposure to a pre-determined UVA dose. Treated water was automatically dispensed into a reservoir tank. The reactor was tested using Escherichia coli as a model pathogen in natural well water. A 6-log inactivation of E. coli was achieved following exposure to the minimum uninterrupted lethal UVA dose. The enhanced reactor decreased the exposure time required to achieve the lethal UVA dose, in comparison to a CPC system with a concentration factor of 1.0. Doubling the lethal UVA dose prevented the need for a period of post-exposure dark inactivation and reduced the overall treatment time. Using this reactor, SODIS can be automatically carried out at an affordable cost, with reduced exposure time and minimal user input. Copyright © 2011 Elsevier B.V. All rights reserved.

[The establishment of environmental endocrine disruptors induced precocious puberty Macaca fascicularis model and the intervention of yin nourishing fire purging Chinese materia medica].

PubMed

Zhu, Lin; Cai, De-pei

2012-12-01

To establish the environmental endocrine disruptors (EEDs) induced precocious puberty macaca fascicularis model, thus verifying the antagonism of yin nourishing fire purging Chinese materia medica (YNFPCMM) against the estrogenic effects. (1) The female prepubescent monkeys at different months old were fed with high dose and low dose EEDs. By observing EEDs' estrogenic effects, the optimal age, the optimal exposure dose, and the optimal exposure time were determined. (2) Fifteen female prepubescent monkeys were randomly divided into the exposure group, the treatment group, and the control group, 5 in each group. Those in the exposure group were fed with EEDs such as nonylphenol (4-NP) and bisphenol A (BPA). Those in the treatment group were fed with EEDs and YNFPCMM. Those in the control group were fed with dissolvent such as corn oil. The therapeutic course was 4 weeks. By the end of the treatment, the serum estrogen level was measured and the maturation index of the vaginal keratinocytes was calculated. The uterus was extracted to measure the wet weight, the endometrial thickness, the ring-shaped myometrium thickness, the endometrial epithelial cells, and the glandular epithelium height. (1) Twenty month was the optimal exposure age. The low dose EEDs was the best exposure dose, and 4 weeks was the optimal exposure time. (2) Compared with the control group, the serum estrogen level obviously increased, the maturation index of the vaginal keratinocytes significantly increased, the wet uterus weight, the endometrial thickness, the ring-shaped myometrium thickness, the endometrial epithelial cells, and the glandular epithelium height significantly increased in the exposure group (P<0.05). Compared with the exposure group, the aforesaid indices significantly decreased in the treatment group (P<0.05). The EEDs induced precocious puberty macaca fascicularis model was successfully established in this study. The EEDs were proved to have estrogenic-like activities. YNFPC-MM was proved to have significant antagonism like estrogenic activities.

A quantitative visual dashboard to explore exposures to ...

EPA Pesticide Factsheets

The Exposure Prioritization (Ex Priori) model features a simplified, quantitative visual dashboard to explore exposures across chemical space. Diverse data streams are integrated within the interface such that different exposure scenarios for “individual,” “population,” or “professional” time-use profiles can be interchanged to tailor exposure and quantitatively explore multi-chemical signatures of exposure, internalized dose (uptake), body burden, and elimination. Ex Priori will quantitatively extrapolate single-point estimates of both exposure and internal dose for multiple exposure scenarios, factors, products, and pathways. Currently, EPA is investigating its usefulness in life cycle analysis, insofar as its ability to enhance exposure factors used in calculating characterization factors for human health. Presented at 2016 Annual ISES Meeting held in Utrecht, The Netherlands, from 9-13 October 2016.

Combined Use of a Patient Dose Monitoring System and a Real-Time Occupational Dose Monitoring System for Fluoroscopically Guided Interventions.

PubMed

Heilmaier, Christina; Kara, Levent; Zuber, Niklaus; Berthold, Christian; Weishaupt, Dominik

2016-04-01

To determine the effect on patient radiation exposure of the combined use of a patient dose monitoring system and real-time occupational dose monitoring during fluoroscopically guided interventions (FGIs). Patient radiation exposure, in terms of the kerma area product (KAP; Gy ∙ cm(2)), was measured in period 1 with a patient dose monitoring system, and a real-time occupational dose monitoring system was additionally applied in period 2. Mean/median KAP in 19 different types of FGIs was analyzed in both periods for two experienced interventional radiologists combined as well as individually. Patient dose and occupational dose were correlated, applying Pearson and Spearman correlation coefficients. Although FGIs were similar in numbers and types over both periods, a substantial decrease was found for period 2 in total mean ± SD/median KAP for both operators together (period 1, 47 Gy ∙ cm(2) ± 67/41 Gy ∙ cm(2); period 2, 37 Gy ∙ cm(2) ± 69/34 Gy ∙ cm(2)) as well as for each individual operator (for all, P < .05). Overall, KAP declined considerably in 15 of 19 types of FGIs in period 2. Mean accumulated dose per intervention was 4.6 µSv, and mean dose rate was 0.24 mSv/h. There was a strong positive correlation between patient and occupational dose (r = 0.88). Combined use of a patient dose monitoring system and a real-time occupational dose monitoring system in FGIs significantly lessens patient and operator doses. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

High-level dietary cadmium exposure is associated with global DNA hypermethylation in the gastropod hepatopancreas

PubMed Central

Popescu, Cristina; Draghici, George A.; Andrica, Florina-Maria; Privistirescu, Ionela A.; Gergen, Iosif I.; Stöger, Reinhard

2017-01-01

5-methylcytosine (5mC) is a key epigenetic mark which influences gene expression and phenotype. In vertebrates, this epigenetic mark is sensitive to Cd exposure, but there is no information linking such an event with changes in global 5mC levels in terrestrial gastropods despite their importance as excellentecotoxicological bioindicators of metal contamination. Therefore, we first evaluated total 5mC content in DNA of the hepatopancreas of adult Cantareus aspersus with the aim to determine whether this epigenetic mark is responsive to Cd exposure. The experiment was conducted under laboratory conditions and involved a continuous exposure, multiple dose- and time-point (14, 28, and 56 days) study design. Hepatopancreas cadmium levels were measured using Flame Atomic Absorption Spectrometry and the percentage of 5-mC in samples using an ELISA-based colorimetric assay. Snail death rates were also assessed. Our results, for the first time, reveal the presence of 5mC in C. aspersus and provide evidence for Cd-induced changes in global 5mC levels in DNA of gastropods and mollusks. Although less sensitive than tissue accumulation, DNA methylation levels responded in a dose- and time-dependent manner to dietary cadmium, with exposure dose having a much stronger effect than exposure duration. An obvious trend of increasing 5mC levels was observed starting at 28 days of exposure to the second highest dose and this trend persisted at the two highest treatments for close to one month, when the experiment was terminated after 56 days. Moreover, a strong association was identified between Cd concentrations in the hepatopancreas and DNA methylation levels in this organ. These data indicate an overall trend towards DNA hypermethylation with elevated Cd exposure. No consistent lethal effect was observed, irrespective of time point and Cd-dosage. Overall, our findings suggest that the total 5mC content in DNA of the hepatopancreas of land snails is responsive to sublethal Cd exposure and give new insights into invertebrate environmental epigenetics. PMID:28877233

How Does Patient Radiation Exposure Compare With Low-dose O-arm Versus Fluoroscopy for Pedicle Screw Placement in Idiopathic Scoliosis?

PubMed

Su, Alvin W; McIntosh, Amy L; Schueler, Beth A; Milbrandt, Todd A; Winkler, Jennifer A; Stans, Anthony A; Larson, A Noelle

Intraoperative C-arm fluoroscopy and low-dose O-arm are both reasonable means to assist in screw placement for idiopathic scoliosis surgery. Both using pediatric low-dose O-arm settings and minimizing the number of radiographs during C-arm fluoroscopy guidance decrease patient radiation exposure and its deleterious biological effect that may be associated with cancer risk. We hypothesized that the radiation dose for C-arm-guided fluoroscopy is no less than low-dose O-arm scanning for placement of pedicle screws. A multicenter matched-control cohort study of 28 patients in total was conducted. Fourteen patients who underwent O-arm-guided pedicle screw insertion for spinal fusion surgery in 1 institution were matched to another 14 patients who underwent C-arm fluoroscopy guidance in the other institution in terms of the age of surgery, body weight, and number of imaged spine levels. The total effective dose was compared. A low-dose pediatric protocol was used for all O-arm scans with an effective dose of 0.65 mSv per scan. The effective dose of C-arm fluoroscopy was determined using anthropomorphic phantoms that represented the thoracic and lumbar spine in anteroposterior and lateral views, respectively. The clinical outcome and complications of all patients were documented. The mean total effective dose for the O-arm group was approximately 4 times higher than that of the C-arm group (P<0.0001). The effective dose for the C-arm patients had high variability based on fluoroscopy time and did not correlate with the number of imaged spine levels or body weight. The effective dose of 1 low-dose pediatric O-arm scan approximated 85 seconds of the C-arm fluoroscopy time. All patients had satisfactory clinical outcomes without major complications that required returning to the operating room. Radiation exposure required for O-arm scans can be higher than that required for C-arm fluoroscopy, but it depends on fluoroscopy time. Inclusion of more medical centers and surgeons will better account for the variability of C-arm dose due to distinct patient characteristics, surgeon's preference, and individual institution's protocol. Level III-case-control study.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryan, E. Ronan, E-mail: ronan@ronanryan.com; Thornton, Raymond; Sofocleous, Constantinos T.

PurposeTo quantify radiation exposure to the primary operator and staff during PET/CT-guided interventional procedures.MethodsIn this prospective study, 12 patients underwent PET/CT-guided interventions over a 6 month period. Radiation exposure was measured for the primary operator, the radiology technologist, and the nurse anesthetist by means of optically stimulated luminescence dosimeters. Radiation exposure was correlated with the procedure time and the use of in-room image guidance (CT fluoroscopy or ultrasound).ResultsThe median effective dose was 0.02 (range 0-0.13) mSv for the primary operator, 0.01 (range 0-0.05) mSv for the nurse anesthetist, and 0.02 (range 0-0.05) mSv for the radiology technologist. The median extremitymore » dose equivalent for the operator was 0.05 (range 0-0.62) mSv. Radiation exposure correlated with procedure duration and with the use of in-room image guidance. The median operator effective dose for the procedure was 0.015 mSv when conventional biopsy mode CT was used, compared to 0.06 mSv for in-room image guidance, although this did not achieve statistical significance as a result of the small sample size (p = 0.06).ConclusionThe operator dose from PET/CT-guided procedures is not significantly different than typical doses from fluoroscopically guided procedures. The major determinant of radiation exposure to the operator from PET/CT-guided interventional procedures is time spent in close proximity to the patient.« less

Cytogenetic damages in peripheral blood of monkey lymphocytes under simulation of cosmonauts irradiation.

NASA Astrophysics Data System (ADS)

Petrov, Vladislav; Ivanov, Alexandr; Barteneva, Svetlana; Snigiryeva, Galina; Shafirkin, Alexandr

Earth modeling of crewmember exposure should be performed for correct estimating radiation hazard during the flight. Such modeling was planned in a monkey experiment for investigating consequences of exposure to a man during an interplanetary flight. It should reflect a chronic impact of galactic cosmic rays and acute and fractional irradiation specified for solar cosmic rays and radiation belts respectively. Due to the difficulty of modeling a chronic impact with the help of a charged particles accelerator it can be used the gamma source. While irradiating big animal groups during a long-term period of time it is preferably to replace chronic irradiation by an equal fractional one. In this case the chosen characteristics of fractional irradiation should ensure the appearances of radiobiological consequences equal to the ones caused by the modeled chronic exposure. So for developing an exposure scheme in the monkey experiment (with Macaca -Rhesus) the model of the acting residual dose, that takes into account repair and recovery processes in the exposed body was used. The total dose value was in the limits from 2.32 Gy up to 3.5 Gy depending on the exposure character. The acting residual dose in all versions of exposure was 2.0 Gy for every monkey. While performing the experiment all the requirements of bioethics for the work with animals were observed. The objects of interest were genomic damages in lymphocytes of monkey's peripheral blood. The data about the CAF during the exposure and at various time moments after exposure particularly directly after the completion of chronicle and fractional irradiation were analyzed. CAF -dose of acute single gamma-irradiation in the range 0 -1.5Gy relationship (calibration curve) was defined in vitro. In addition the rate of the aberrant cells elimination within three months after the irradiation completion was estimated. On the basis of the obtained CAF data we performed verification of applicability of cytogenetic analysis for estimating the monkey gamma -dose exposure in the experiment It was obtained that this method permits to estimate the acting residual dose with accuracy of 30

High-resolution short-exposure small-animal laboratory x-ray phase-contrast tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larsson, Daniel H.; Vågberg, William; Yaroshenko, Andre

X-ray computed tomography of small animals and their organs is an essential tool in basic and preclinical biomedical research. In both phase-contrast and absorption tomography high spatial resolution and short exposure times are of key importance. However, the observable spatial resolutions and achievable exposure times are presently limited by system parameters rather than more fundamental constraints like, e.g., dose. Here we demonstrate laboratory tomography with few-ten μm spatial resolution and few-minute exposure time at an acceptable dose for small-animal imaging, both with absorption contrast and phase contrast. The method relies on a magnifying imaging scheme in combination with a high-powermore » small-spot liquid-metal-jet electron-impact source. Lastly, the tomographic imaging is demonstrated on intact mouse, phantoms and excised lungs, both healthy and with pulmonary emphysema.« less

High-resolution short-exposure small-animal laboratory x-ray phase-contrast tomography

DOE PAGES

Larsson, Daniel H.; Vågberg, William; Yaroshenko, Andre; ...

2016-12-13

X-ray computed tomography of small animals and their organs is an essential tool in basic and preclinical biomedical research. In both phase-contrast and absorption tomography high spatial resolution and short exposure times are of key importance. However, the observable spatial resolutions and achievable exposure times are presently limited by system parameters rather than more fundamental constraints like, e.g., dose. Here we demonstrate laboratory tomography with few-ten μm spatial resolution and few-minute exposure time at an acceptable dose for small-animal imaging, both with absorption contrast and phase contrast. The method relies on a magnifying imaging scheme in combination with a high-powermore » small-spot liquid-metal-jet electron-impact source. Lastly, the tomographic imaging is demonstrated on intact mouse, phantoms and excised lungs, both healthy and with pulmonary emphysema.« less

Acute toxicity, biochemical and histopathological responses of endosulfan in Chanos chanos.

PubMed

Kumar, Neeraj; Ambasankar, K; Krishnani, K K; Gupta, S K; Bhushan, Shashi; Minhas, P S

2016-09-01

This study investigated 96h median lethal concentration of endosulfan (99%, pure α: β ratio of 7:3) by conducting static non-renewable acute toxicity bio-assay in Chanos chanos juvenile with average weight (110±5.65g). Further, the effect of different definitive doses (18.5, 19.5, 20.5, 21.5 and 22.5µg/L) of endosulfan on metabolic, heamato-immunoligcal and histopathological response were probed. Anti-oxidative enzymes CAT, SOD and GST showed significant (p<0.01) increase of activity in the liver, gill and brain during exposure to endosulfan in a dose and time dependent manner. The brain AChE activity showed significant (p<0.01) inhibition from 18.5 to 22.5µg/L exposure of endosulfan than the control group. LDH and MDH activity gradually increased with consequent increasing dose of endosulfan exposure in the liver, gill and brain. Similarly, ALT, AST and G6PDH activities in both liver and gill increased with consequent increases in the dose of endosulfan exposure. Immunological profile such as blood glucose and serum cortisol level significantly enhanced while respiratory burst activity declined with consequent increasing doses of endosulfan exposure. Histopathological alteration in the gill demonstrated curling of secondary lamellae, thickening of primary epithelium, shorting of secondary lamellae, epithelial hyperplasia, fusion of secondary lamellae, aneurism, and collapsed secondary lamellae due to dose dependent exposure of endosulfan. Liver histology illustrated cloudy swelling and necrosis with pyknotic nuclei to the moderate dose of endosulfan, whereas higher dose of endosulfan (21.5µg/L) displayed severe necrosis of hepatic cells. Overall results clearly indicate that acute exposure of endosulfan led to pronounced deleterious alterations on biochemical, heamato-immunological, and histopathological responses of C. chanos juvenile. Copyright © 2016 Elsevier Inc. All rights reserved.

MO-F-CAMPUS-I-01: A System for Automatically Calculating Organ and Effective Dose for Fluoroscopically-Guided Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiong, Z; Vijayan, S; Rana, V

2015-06-15

Purpose: A system was developed that automatically calculates the organ and effective dose for individual fluoroscopically-guided procedures using a log of the clinical exposure parameters. Methods: We have previously developed a dose tracking system (DTS) to provide a real-time color-coded 3D- mapping of skin dose. This software produces a log file of all geometry and exposure parameters for every x-ray pulse during a procedure. The data in the log files is input into PCXMC, a Monte Carlo program that calculates organ and effective dose for projections and exposure parameters set by the user. We developed a MATLAB program to readmore » data from the log files produced by the DTS and to automatically generate the definition files in the format used by PCXMC. The processing is done at the end of a procedure after all exposures are completed. Since there are thousands of exposure pulses with various parameters for fluoroscopy, DA and DSA and at various projections, the data for exposures with similar parameters is grouped prior to entry into PCXMC to reduce the number of Monte Carlo calculations that need to be performed. Results: The software developed automatically transfers data from the DTS log file to PCXMC and runs the program for each grouping of exposure pulses. When the dose from all exposure events are calculated, the doses for each organ and all effective doses are summed to obtain procedure totals. For a complicated interventional procedure, the calculations can be completed on a PC without manual intervention in less than 30 minutes depending on the level of data grouping. Conclusion: This system allows organ dose to be calculated for individual procedures for every patient without tedious calculations or data entry so that estimates of stochastic risk can be obtained in addition to the deterministic risk estimate provided by the DTS. Partial support from NIH grant R01EB002873 and Toshiba Medical Systems Corp.« less

Achieving Consistent Multiple Daily Low-Dose Bacillus anthracis Spore Inhalation Exposures in the Rabbit Model

PubMed Central

Barnewall, Roy E.; Comer, Jason E.; Miller, Brian D.; Gutting, Bradford W.; Wolfe, Daniel N.; Director-Myska, Alison E.; Nichols, Tonya L.; Taft, Sarah C.

2012-01-01

Repeated low-level exposures to biological agents could occur before or after the remediation of an environmental release. This is especially true for persistent agents such as B. anthracis spores, the causative agent of anthrax. Studies were conducted to examine aerosol methods needed for consistent daily low aerosol concentrations to deliver a low-dose (less than 106 colony forming units (CFU) of B. anthracis spores) and included a pilot feasibility characterization study, acute exposure study, and a multiple 15 day exposure study. This manuscript focuses on the state-of-the-science aerosol methodologies used to generate and aerosolize consistent daily low aerosol concentrations and resultant low inhalation doses to rabbits. The pilot feasibility characterization study determined that the aerosol system was consistent and capable of producing very low aerosol concentrations. In the acute, single day exposure experiment, targeted inhaled doses of 1 × 102, 1 × 103, 1 × 104, and 1 × 105 CFU were used. In the multiple daily exposure experiment, rabbits were exposed multiple days to targeted inhaled doses of 1 × 102, 1 × 103, and 1 × 104 CFU. In all studies, targeted inhaled doses remained consistent from rabbit-to-rabbit and day-to-day. The aerosol system produced aerosolized spores within the optimal mass median aerodynamic diameter particle size range to reach deep lung alveoli. Consistency of the inhaled dose was aided by monitoring and recording respiratory parameters during the exposure with real-time plethysmography. Overall, the presented results show that the animal aerosol system was stable and highly reproducible between different studies and over multiple exposure days. PMID:22919662

Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

PubMed

Madas, Balázs G

2016-07-01

Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

Imidacloprid exposure cause the histopathological changes, activation of TNF-α, iNOS, 8-OHdG biomarkers, and alteration of caspase 3, iNOS, CYP1A, MT1 gene expression levels in common carp (Cyprinus carpio L.).

PubMed

Özdemir, Selçuk; Altun, Serdar; Arslan, Harun

2018-01-01

Imidacloprid (IMI) is a neonicotinoid that is widely used for the protection of crops and carnivores from insects and parasites, respectively. It is well known that imidacloprid exposure has a harmful effect on several organisms. However, there is little information about imidacloprid toxicity in aquatic animals, particularly fish. Thus, in the current study, we assessed the histopathological changes; activation of iNOS, 8-OHdG and TNF-α; and expression levels of caspase 3, iNOS, CYP1A and MT1 genes in the common carp exposed to imidacloprid. For this purpose, fish were exposed to either a low dose (140 mg/L) or a high dose (280 mg/L) of imidacloprid for 24 h, 48 h, 72 h and 96 h. After IMI exposure, we detected hyperplasia of secondary lamellar cells and mucous cell hyperplasia in the gills, as well as hydropic degeneration in hepatocytes and necrosis in the liver. Moreover, 8-OHdG, iNOS and TNF-α activation was found particularly in the gills and liver but also moderately in the brain. Transcriptional analysis showed that caspase 3 expression was altered low dose and high doses of IMI for 72 h and 96 h exposure ( p <  0.05), iNOS expression was up-regulated with both low and high doses of IMI and in a time-dependent manner ( p <  0.05, p <  0.01, p <  0.001), CYP1A expression was not significantly changed regardless of the dose of IMI and exposure time ( p >  0.05) except with low and high doses of IMI for 96 h ( p <  0.05), and lastly, MT1 gene expression was up-regulated only in the brain with low doses of IMI for 96 h and high doses of IMI for 48 h, 72 h and 96 h exposure ( p <  0.05, p <  0.01). Our results indicated that acute IMI exposure moderately induce apoptosis in the brain but caused severe histopathological lesions, inflammation, and oxidative stress in the gills, liver, and brain of the common carp.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berrington de Gonzalez, Amy, E-mail: berringtona@mail.nih.gov; Gilbert, Ethel; Curtis, Rochelle

Rapid innovations in radiation therapy techniques have resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, because direct observation of the late effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1-5 Gy). In particular, there is uncertainty about the shape of the dose-response curve at high doses and about the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studiesmore » of second solid cancers in organs that received high-dose exposure (>5 Gy) from radiation therapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was nonlinear in the direction of a downturn in risk, even at organ doses of ≥60 Gy. Thyroid cancer was the only exception, with evidence of a downturn after 20 Gy. Generally the excess relative risk per Gray, taking account of age and sex, was 5 to 10 times lower than the risk from acute exposures of <2 Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to the second cancer. The results of our review provide insights into radiation carcinogenesis from fractionated high-dose exposures and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiation therapy techniques.« less

Exposure to fine particulate, black carbon, and particle number concentration in transportation microenvironments

NASA Astrophysics Data System (ADS)

Morales Betancourt, R.; Galvis, B.; Balachandran, S.; Ramos-Bonilla, J. P.; Sarmiento, O. L.; Gallo-Murcia, S. M.; Contreras, Y.

2017-05-01

This research determined intake dose of fine particulate matter (PM2.5), equivalent black carbon (eBC), and number of sub-micron particles (Np) for commuters in Bogotá, Colombia. Doses were estimated through measurements of exposure concentration, a surrogate of physical activity, as well as travel times and speeds. Impacts of travel mode, traffic load, and street configuration on dose and exposure were explored. Three road segments were selected because of their different traffic loads and composition, and dissimilar street configuration. The transport modes considered include active modes (walking and cycling) and motorized modes (bus, car, taxi, and motorcycle). Measurements were performed simultaneously in the available modes at each road segment. High average eBC concentrations were observed throughout the campaign, ranging from 20 to 120 μgm-3 . Commuters in motorized modes experienced significantly higher exposure concentrations than pedestrians and bicyclists. The highest average concentrations of PM2.5, eBC , and Np were measured inside the city's Bus Rapid Transit (BRT) system vehicles. Pedestrians and bicycle users in an open street configuration were exposed to the lowest average concentrations of PM2.5 and eBC , six times lower than those experienced by commuters using the BRT in the same street segment. Pedestrians experienced the highest particulate matter intake dose in the road segments studied, despite being exposed to lower concentrations than commuters in motorized modes. Average potential dose of PM2.5 and eBC per unit length traveled were nearly three times higher for pedestrians in a street canyon configuration compared to commuters in public transport. Slower travel speed and elevated inhalation rates dominate PM dose for pedestrians. The presence of dedicated bike lanes on sidewalks has a significant impact on reducing the exposure concentration for bicyclists compared to those riding in mixed traffic lanes. This study proposes a simple method to perform loading effect correction for measurements of black carbon using multiple portable aethalometers.

Chronic Low Dose Chlorine Exposure Aggravates Allergic Inflammation and Airway Hyperresponsiveness and Activates Inflammasome Pathway

PubMed Central

Kim, Sae-Hoon; Park, Da-Eun; Lee, Hyun-Seung; Kang, Hye-Ryun; Cho, Sang-Heon

2014-01-01

Background Epidemiologic clinical studies suggested that chronic exposure to chlorine products is associated with development of asthma and aggravation of asthmatic symptoms. However, its underlying mechanism was not clearly understood. Studies were undertaken to define the effects and mechanisms of chronic low-dose chlorine exposure in the pathogenesis of airway inflammation and airway hyperresponsiveness (AHR). Methods Six week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure of naturally vaporized gas of 5% sodium hypochlorite solution. Airway inflammation and AHR were evaluated by bronchoalveolar lavage (BAL) cell recovery and non-invasive phlethysmography, respectively. Real-time qPCR, Western blot assay, and ELISA were used to evaluate the mRNA and protein expressions of cytokines and other inflammatory mediators. Human A549 and murine epithelial (A549 and MLE12) and macrophage (AMJ2-C11) cells were used to define the responses to low dose chlorine exposure in vitro. Results Chronic low dose chlorine exposure significantly augmented airway inflammation and AHR in OVA-sensitized and challenged mice. The expression of Th2 cytokines IL-4 and IL-5 and proinflammatory cytokine IL-1β and IL-33 were significantly increased in OVA/Cl group compared with OVA group. The chlorine exposure also activates the major molecules associated with inflammasome pathway in the macrophages with increased expression of epithelial alarmins IL-33 and TSLP in vitro. Conclusion Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways. PMID:25202911

Whole mouse blood microRNA as biomarkers for exposure to γ-rays and 56Fe ions

PubMed Central

Templin, Thomas; Amundson, Sally A.; Brenner, David J.; Smilenov, Lubomir B.

2013-01-01

Purpose Biomarkers of ionising radiation exposure are useful in a variety of scenarios, such as medical diagnostic imaging, occupational exposures, and spaceflight. This study investigates to what extent microRNA (miRNA) expression signatures in mouse peripheral blood can be used as biomarkers for exposures to radiation with low and high linear energy transfers. Materials and methods Mice were irradiated with doses of 0.5, 1.5, or 5.0 Gy γ-rays (dose rate of 0.0136 Gy/s) or with doses of 0.1 or 0.5 Gy 56Fe ions (dose rate of 0.00208 Gy/s). Total RNA was isolated from whole blood at 6 h or 24 h after irradiation. Three animals per irradiation condition were used. Differentially expressed miRNA were determined by means of quantitative real-time polymerase chain reaction. Results miRNA expression signatures were radiation type-specific and dose- and time-dependent. The differentially expressed miRNA were expressed in either one condition (71%) or multiple conditions (29%). Classifiers based on the differentially expressed miRNA predicted radiation type or dose with accuracies between 75% and 100%. Gene-ontology analyses show that miRNA induced by irradiation are involved in the control of several biological processes, such as mRNA transcription regulation, nucleic-acid metabolism, and development. Conclusion miRNA signatures induced by ionising radiation in mouse blood are radiation type- and radiation dose-specific. These findings underline the complexity of the radiation response and the importance of miRNA in it. PMID:21271940

The need for non- or minimally-invasive biomonitoring strategies and the development of pharmacokinetic/pharmacodynamic models for quantification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timchalk, Charles; Weber, Thomas J.; Smith, Jordan N.

Advancements in Exposure Science involving the development and deployment of biomarkers of exposure and biological response are anticipated to significantly (and positively) influence health outcomes associated with occupational, environmental and clinical exposure to chemicals/drugs. To achieve this vision, innovative strategies are needed to develop multiplex sensor platforms capable of quantifying individual and mixed exposures (i.e. systemic dose) by measuring biomarkers of dose and biological response in readily obtainable (non-invasive) biofluids. Secondly, the use of saliva (alternative to blood) for biomonitoring coupled with the ability to rapidly analyze multiple samples in real-time offers an innovative opportunity to revolutionize biomonitoring assessments. Inmore » this regard, the timing and number of samples taken for biomonitoring will not be limited as is currently the case. In addition, real-time analysis will facilitate identification of work practices or conditions that are contributing to increased exposures and will make possible a more rapid and successful intervention strategy. The initial development and application of computational models for evaluation of saliva/blood analyte concentration at anticipated exposure levels represents an important opportunity to establish the limits of quantification and robustness of multiplex sensor systems by exploiting a unique computational modeling framework. The use of these pharmacokinetic models will also enable prediction of an exposure dose based on the saliva/blood measurement. This novel strategy will result in a more accurate prediction of exposures and, once validated, can be employed to assess dosimetry to a broad range of chemicals in support of biomonitoring and epidemiology studies.« less

Evaluation of automatic exposure control system chamber for the dose optimization when examining pelvic in digital radiography.

PubMed

Kim, Sung-Chul; Lee, Hae-Kag; Lee, Yang-Sub; Cho, Jae-Hwan

2015-01-01

We found a way to optimize the image quality and reduce the exposure dose of patients through the proper activity combination of the automatic exposure control system chamber for the dose optimization when examining the pelvic anteroposterior side using the phantom of the human body standard model. We set 7 combinations of the chamber of automatic exposure control system. The effective dose was yielded by measuring five times for each according to the activity combination of the chamber for the dose measurement. Five radiologists with more than five years of experience evaluated the image through picture archiving and communication system using double blind test while classifying the 6 anatomical sites into 3-point level (improper, proper, perfect). When only one central chamber was activated, the effective dose was found to be the highest level, 0.287 mSv; and lowest when only the top left chamber was used, 0.165 mSv. After the subjective evaluation by five panel members on the pelvic image was completed, there was no statistically meaningful difference between the 7 chamber combinations, and all had good image quality. When testing the pelvic anteroposterior side with digital radiography, we were able to reduce the exposure dose of patients using the combination of the top right side of or the top two of the chamber.

Electron spin resonance analysis of tooth enamel does not indicate exposures to large radiation doses in a large proportion of distally-exposed A-bomb survivors.

PubMed

Hirai, Yuko; Kodama, Yoshiaki; Cullings, Harry M; Miyazawa, Chuzo; Nakamura, Nori

2011-01-01

The atomic bombs in Hiroshima and Nagasaki led to two different types of radiation exposure; one was direct and brief and the other was indirect and persistent. The latter (so-called exposure to residual radiation) resulted from the presence of neutron activation products in the soil, or from fission products present in the fallout. Compared with the doses from direct exposures, estimations of individual doses from residual radiation have been much more complicated, and estimates vary widely among researchers. The present report bases its conclusions on radiation doses recorded in tooth enamel from survivors in Hiroshima. Those survivors were present at distances of about 3 km or greater from the hypocenter at the time of the explosion, and have DS02 estimated doses (direct exposure doses) of less than 5 mGy (and are regarded as control subjects). Individual doses were estimated by measuring CO(2)(-) radicals in tooth enamel with the electron spin resonance (ESR; or electron paramagnetic resonance, EPR) method. The results from 56 molars donated by 49 survivors provided estimated doses which vary from -200 mGy to 500 mGy, and the median dose was 17 mGy (25% and 75% quartiles are -54 mGy and 137 mGy, respectively) for the buccal parts and 13 mGy (25% and 75% quartiles: -49 mGy and 87 mGy, respectively) for the lingual parts of the molars. Three molars had ESR-estimated doses of 300 to 400 mGy for both the buccal and lingual parts, which indicates possible exposures to excess doses of penetrating radiation, although the origin of such radiation remains to be determined. The results did not support claims that a large fraction of distally-exposed survivors received large doses (e.g. 1 Gy) of external penetrating radiation resulting from residual radiation.

Metabolomics reveals dose effects of low-dose chronic exposure to uranium in rats: identification of candidate biomarkers in urine samples.

PubMed

Grison, Stéphane; Favé, Gaëlle; Maillot, Matthieu; Manens, Line; Delissen, Olivia; Blanchardon, Éric; Dublineau, Isabelle; Aigueperse, Jocelyne; Bohand, Sandra; Martin, Jean-Charles; Souidi, Maâmar

2016-01-01

Data are sparse about the potential health risks of chronic low-dose contamination of humans by uranium (natural or anthropogenic) in drinking water. Previous studies report some molecular imbalances but no clinical signs due to uranium intake. In a proof-of-principle study, we reported that metabolomics is an appropriate method for addressing this chronic low-dose exposure in a rat model (uranium dose: 40 mg L -1 ; duration: 9 months, n = 10). In the present study, our aim was to investigate the dose-effect pattern and identify additional potential biomarkers in urine samples. Compared to our previous protocol, we doubled the number of rats per group (n = 20), added additional sampling time points (3 and 6 months) and included several lower doses of natural uranium (doses used: 40, 1.5, 0.15 and 0.015 mg L -1 ). LC-MS metabolomics was performed on urine samples and statistical analyses were made with SIMCA-P+ and R packages. The data confirmed our previous results and showed that discrimination was both dose and time related. Uranium exposure was revealed in rats contaminated for 9 months at a dose as low as 0.15 mg L -1 . Eleven features, including the confidently identified N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide and 4-hydroxyphenylacetylglycine, discriminated control from contaminated rats with a specificity and a sensitivity ranging from 83 to 96 %, when combined into a composite score. These findings show promise for the elucidation of underlying radiotoxicologic mechanisms and the design of a diagnostic test to assess exposure in urine, in a dose range experimentally estimated to be above a threshold between 0.015 and 0.15 mg L -1 .

Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC.

PubMed

Karschner, Erin L; Schwope, David M; Schwilke, Eugene W; Goodwin, Robert S; Kelly, Deanna L; Gorelick, David A; Huestis, Marilyn A

2012-10-01

Determining time since last cannabis/Δ9-tetrahydrocannabinol (THC) exposure is important in clinical, workplace, and forensic settings. Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P) ratio. No studies previously evaluated predictive models utilizing empirically-derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic THC dosing. Ten male chronic, daily cannabis smokers received escalating around-the-clock oral THC (40-120 mg daily) for 8 days. Cannabinoids were quantified in whole blood and plasma by two-dimensional gas chromatography-mass spectrometry. Maximum whole blood THC occurred 3.0 h after the first oral THC dose and 103.5h (4.3 days) during multiple THC dosing. Median WB/P ratios were THC 0.63 (n=196), 11-hydroxy-THC 0.60 (n=189), and 11-nor-9-carboxy-THC (THCCOOH) 0.55 (n=200). Predictive models utilizing these WB/P ratios accurately estimated last cannabis exposure in 96% and 100% of specimens collected within 1-5h after a single oral THC dose and throughout multiple dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5h after the last THC dose, respectively. Predictive models estimating time since last cannabis intake from whole blood and plasma cannabinoid concentrations were inaccurate during abstinence, but highly accurate during active THC dosing. THC redistribution from large cannabinoid body stores and high circulating THCCOOH concentrations create different pharmacokinetic profiles than those in less than daily cannabis smokers that were used to derive the models. Thus, the models do not accurately predict time of last THC intake in individuals consuming THC daily. Published by Elsevier Ireland Ltd.

Design of the Experimental Exposure Conditions to Simulate Ionizing Radiation Effects on Candidate Replacement Materials for the Hubble Space Telescope

NASA Technical Reports Server (NTRS)

Smith, L. Montgomery

1998-01-01

In this effort, experimental exposure times for monoenergetic electrons and protons were determined to simulate the space radiation environment effects on Teflon components of the Hubble Space Telescope. Although the energy range of the available laboratory particle accelerators was limited, optimal exposure times for 50 keV, 220 keV, 350 keV, and 500 KeV electrons were calculated that produced a dose-versus-depth profile that approximated the full spectrum profile, and were realizable with existing equipment. For the case of proton exposure, the limited energy range of the laboratory accelerator restricted simulation of the dose to a depth of .5 mil. Also, while optimal exposure times were found for 200 keV, 500 keV and 700 keV protons that simulated the full spectrum dose-versus-depth profile to this depth, they were of such short duration that the existing laboratory could not be controlled to within the required accuracy. In addition to the obvious experimental issues, other areas exist in which the analytical work could be advanced. Improved computer codes for the dose prediction- along with improved methodology for data input and output- would accelerate and make more accurate the calculational aspects. This is particularly true in the case of proton fluxes where a paucity of available predictive software appears to exist. The dated nature of many of the existing Monte Carlo particle/radiation transport codes raises the issue as to whether existing codes are sufficient for this type of analysis. Other areas that would result in greater fidelity of laboratory exposure effects to the space environment is the use of a larger number of monoenergetic particle fluxes and improved optimization algorithms to determine the weighting values.

Maternal Methadone Dose, Placental Methadone Concentrations, and Neonatal Outcomes

PubMed Central

de Castro, Ana; Jones, Hendreé E.; Johnson, Rolley E.; Gray, Teresa R.; Shakleya, Diaa M.; Huestis, Marilyn A.

2015-01-01

BACKGROUND Few investigations have used placenta as an alternative matrix to detect in utero drug exposure, despite its availability at the time of birth and the large amount of sample. Methadone-maintained opioid-dependent pregnant women provide a unique opportunity to examine the placental disposition of methadone and metabolite [2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)], to explore their correlations with maternal methadone dose and neonatal outcomes, and to test the ability to detect in utero exposure to illicit drugs. METHODS We calculated the correlations of placental methadone and EDDP concentrations and their correlations with maternal methadone doses and neonatal outcomes. Cocaine- and opiate-positive placenta results were compared with the results for meconium samples and for urine samples collected throughout gestation. RESULTS Positive correlations were found between placental methadone and EDDP concentrations (r = 0.685), and between methadone concentration and methadone dose at delivery (r = 0.542), mean daily dose (r = 0.554), mean third-trimester dose (r = 0.591), and cumulative daily dose (r = 0.639). The EDDP/methadone concentration ratio was negatively correlated with cumulative daily dose (r = 0.541) and positively correlated with peak neonatal abstinence syndrome (NAS) score (r = 0.513). Placental EDDP concentration was negatively correlated with newborn head circumference (r = 0.579). Cocaine and opiate use was detected in far fewer placenta samples than in thrice-weekly urine and meconium samples, a result suggesting a short detection window for placenta. CONCLUSIONS Quantitative methadone and EDDP measurement may predict NAS severity. The placenta reflects in utero drug exposure for a shorter time than meconium but may be useful when meconium is unavailable or if documentation of recent exposure is needed. PMID:21245372

Radiation exposure and safety practices during pediatric central line placement

PubMed Central

Saeman, Melody R.; Burkhalter, Lorrie S.; Blackburn, Timothy J.; Murphy, Joseph T.

2015-01-01

Purpose Pediatric surgeons routinely use fluoroscopy for central venous line (CVL) placement. We examined radiation safety practices and patient/surgeon exposure during fluoroscopic CVL. Methods Fluoroscopic CVL procedures performed by 11 pediatric surgeons in 2012 were reviewed. Fluoroscopic time (FT), patient exposure (mGy), and procedural data were collected. Anthropomorphic phantom simulations were used to calculate scatter and dose (mSv). Surgeons were surveyed regarding safety practices. Results 386 procedures were reviewed. Median FT was 12.8 seconds. Median patient estimated effective dose was 0.13 mSv. Median annual FT per surgeon was 15.4 minutes. Simulations showed no significant difference (p = 0.14) between reported exposures (median 3.5 mGy/min) and the modeled regression exposures from the C-arm default mode (median 3.4 mGy/min). Median calculated surgeon exposure was 1.5 mGy/year. Eight of 11 surgeons responded to the survey. Only three reported 100% lead protection and frequent dosimeter use. Conclusion We found non-standard radiation training, safety practices, and dose monitoring for the 11 surgeons. Based on simulations, the C-arm default setting was typically used instead of low dose. While most CVL procedures have low patient/surgeon doses, every effort should be used to minimize patient and occupational exposure, suggesting the need for formal hands-on training for non-radiologist providers using fluoroscopy. PMID:25837269

Environmental factors associated with a spectrum of neurodevelopmental deficits.

PubMed

Mendola, Pauline; Selevan, Sherry G; Gutter, Suzanne; Rice, Deborah

2002-01-01

A number of environmental agents have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. Critical windows of vulnerability to the effects of these agents occur both pre- and postnatally. The nervous system is relatively unique in that different parts are responsible for different functional domains, and these develop at different times (e.g., motor control, sensory, intelligence and attention). In addition, the many cell types in the brain have different windows of vulnerability with varying sensitivities to environmental agents. This review focuses on two environmental agents, lead and methylmercury, to illustrate the neurobehavioral and cognitive effects that can result from early life exposures. Special attention is paid to distinguishing between the effects detected following episodes of poisoning and those detected following lower dose exposures. Perinatal and childhood exposure to high doses of lead results in encephalopathy and convulsions. Lower-dose lead exposures have been associated with impairment in intellectual function and attention. At high levels of prenatal exposure, methylmercury produces mental retardation, cerebral palsy and visual and auditory deficits in children of exposed mothers. At lower levels of methylmercury exposure, the effects in children have been more subtle. Other environmental neurotoxicants that have been shown to produce developmental neurotoxicity include polychlorinated biphenyls (PCBs), dioxins, pesticides, ionizing radiation, environmental tobacco smoke, and maternal use of alcohol, tobacco, marijuana and cocaine. Exposure to environmental agents with neurotoxic effects can result in a spectrum of adverse outcomes from severe mental retardation and disability to more subtle changes in function depending on the timing and dose of the chemical agent. Copyright 2002 Wiley-Liss, Inc.

A dose-responsive model of smoke inhalation injury. Severity-related alteration in cardiopulmonary function.

PubMed Central

Shimazu, T; Yukioka, T; Hubbard, G B; Langlinais, P C; Mason, A D; Pruitt, B A

1987-01-01

The dose responsiveness of selected physiologic indices was studied in a sheep model of smoke inhalation injury. In this model, graded severity of injury was achieved by changing the contact time with smoke (defined by "unit"), whereas other variables were kept constant. Blood gas and cardiopulmonary indices were measured in 70 sheep, including 12 controls, either 24 or 72 hours after exposure to 3, 6, 9, 12, 15, or 18 units of smoke. A 12-unit dose of smoke was fatal within 72 hours and an 18-unit dose was fatal within 24 hours. The best correlation between smoke dose and response was observed in arterial oxygen tension 24 hours after exposure. At 24 hours, most of the cardiopulmonary indices showed significant change only after a 12-unit exposure. Although the exact shape of the dose-response curve could not be defined, sigmoid or curved linear shape was suggested, reflecting the progressive deterioration. Images Fig. 3. Fig. 4A. Fig. 4B. PMID:3606236

The effects of proton radiation on the prothrombin and partial thromboplastin times of irradiated ferrets

PubMed Central

Krigsfeld, Gabriel S.; Sanzari, Jenine K.; Kennedy, Ann R.

2013-01-01

Purpose To determine whether proton radiation affects coagulation. Material and methods Ferrets were exposed to solar particle event-like proton radiation at doses of 0, 25, 100, or 200 centigray (cGy), and dose rates of 50 cGy/minute (high dose rate or HDR) or 50 cGy/hour (low dose rate or LDR). Plasma was isolated from blood collected prior to radiation exposure and at 3–7 h post-radiation. Prothrombin time (PT) assays and activated partial thromboplastin time (aPTT) assays were performed as were mixing studies to determine the coagulation factors involved. Results HDR and LDR exposure led to statistically significant increases in PT values. It was determined that the HDR-induced increase in PT was due to Factor VII, while Factors II, V, and VII contributed to the LDR-induced increase in PT values. Only acute LDR exposure caused an increase in aPTT values, which remained elevated for 48 h post-irradiation (which was the latest time assayed in these studies). Mixing studies revealed that Factor IX contributed to the increased aPTT values. A majority of the animals exposed at the LDR had an International Normalized Ratio approaching or surpassing 2.0. Conclusions PT/aPTT assays resulted in increased clotting times due to different coagulation factors, indicating potential radiation-induced coagulopathy. PMID:22221163

Particle exposure and inhaled dose during commuting in Singapore

NASA Astrophysics Data System (ADS)

Tan, Sok Huang; Roth, Matthias; Velasco, Erik

2017-12-01

Exposure concentration and inhaled dose of particles during door-to-door trips walking and using motorized transport modes (subway, bus, taxi) are evaluated along a selected route in a commercial district of Singapore. Concentrations of particles smaller than 2.5 μm in size (PM2.5), black carbon, particle-bound polycyclic aromatic hydrocarbons, number of particles, active surface area and carbon monoxide have been measured in-situ using portable instruments. Simultaneous measurements were conducted at a nearby park to capture the background concentrations. The heart rate of the participants was monitored during the measurements as a proxy of the inhalation rate used to calculate the inhaled dose of particles. All measured metrics were highest and well above background levels during walking. No significant difference was observed in the exposure concentration of PM2.5 for the three motorized transport modes, unlike for the metrics associated with ultrafine particles (UFP). The concentration of these freshly emitted particles was significantly lower on subway trips. The absence of combustion sources, use of air conditioning and screen doors at station platforms are effective measures to protect passengers' health. For other transport modes, sections of trips close to accelerating and idling vehicles, such as bus stops, traffic junctions and taxi stands, represent hotspots of particles. Reducing the waiting time at such locations will lower pollutants exposure and inhaled dose during a commute. After taking into account the effect of inhalation and travel duration when calculating dose, the health benefit of commuting by subway for this particular district of Singapore became even more evident. For example, pedestrians breathe in 2.6 and 3.2 times more PM2.5 and UFP, respectively than subway commuters. Public buses were the second best alternative. Walking emerged as the worst commuting mode in terms of particle exposure and inhaled dose.

SUDOQU, a new dose-assessment methodology for radiological surface contamination.

PubMed

van Dillen, Teun; van Dijk, Arjan

2018-06-12

A new methodology has been developed for the assessment of the annual effective dose resulting from removable and fixed radiological surface contamination. It is entitled SUDOQU (SUrface DOse QUantification) and it can for instance be used to derive criteria for surface contamination related to the import of non-food consumer goods, containers and conveyances, e.g., limiting values and operational screening levels. SUDOQU imposes mass (activity)-balance equations based on radioactive decay, removal and deposition processes in indoor and outdoor environments. This leads to time-dependent contamination levels that may be of particular importance in exposure scenarios dealing with one or a few contaminated items only (usually public exposure scenarios, therefore referred to as the 'consumer' model). Exposure scenarios with a continuous flow of freshly contaminated goods also fall within the scope of the methodology (typically occupational exposure scenarios, thus referred to as the 'worker model'). In this paper we describe SUDOQU, its applications, and its current limitations. First, we delineate the contamination issue, present the assumptions and explain the concepts. We describe the relevant removal, transfer, and deposition processes, and derive equations for the time evolution of the radiological surface-, air- and skin-contamination levels. These are then input for the subsequent evaluation of the annual effective dose with possible contributions from external gamma radiation, inhalation, secondary ingestion (indirect, from hand to mouth), skin contamination, direct ingestion and skin-contact exposure. The limiting effective surface dose is introduced for issues involving the conservatism of dose calculations. SUDOQU can be used by radiation-protection scientists/experts and policy makers in the field of e.g. emergency preparedness, trade and transport, exemption and clearance, waste management, and nuclear facilities. Several practical examples are worked out demonstrating the potential applications of the methodology. . Creative Commons Attribution license.

[Evaluation of Radiation Dose during Stent-graft Treatment Using a Hybrid Operating Room System].

PubMed

Haga, Yoshihiro; Chida, Kouichi; Kaga, Yuji; Saitou, Kazuhisa; Arai, Takeshi; Suzuki, Shinichi; Iwaya, Yoshimi; Kumasaka, Eriko; Kataoka, Nozomi; Satou, Naoto; Abe, Mitsuya

2015-12-01

In recent years, aortic aneurysm treatment with stent graft grafting in the X-ray fluoroscopy is increasing. This is an endovascular therapy, because it is a treatment which includes the risk of radiation damage, having to deal with radiation damage, to know in advance is important. In this study, in order to grasp the trend of exposure stent graft implantation in a hybrid operating room (OR) system, focusing on clinical data (entrance skin dose and fluoroscopy time), was to count the total. In TEVAR and EVAR, fluoroscopy time became 13.40 ± 7.27 minutes, 23.67 ± 11.76 minutes, ESD became 0.87 ± 0.41 mGy, 1.11 ± 0.57 mGy. (fluoroscopy time of EVAR was 2.0 times than TEVAR. DAP of EVAR was 1.2 times than TEVAR.) When using the device, adapted lesions and usage are different. This means that care changes in exposure-related factors. In this study, exposure trends of the stent graft implantation was able to grasp. It can be a helpful way to reduce/optimize the radiation dose in a hybrid OR system.

ICRP PUBLICATION 122: radiological protection in geological disposal of long-lived solid radioactive waste.

PubMed

Weiss, W; Larsson, C-M; McKenney, C; Minon, J-P; Mobbs, S; Schneider, T; Umeki, H; Hilden, W; Pescatore, C; Vesterlind, M

2013-06-01

This report updates and consolidates previous recommendations of the International Commission on Radiological Protection (ICRP) related to solid waste disposal (ICRP, 1985, 1997b, 1998). The recommendations given apply specifically to geological disposal of long-lived solid radioactive waste. The report explains how the ICRP system of radiological protection described in Publication 103 (ICRP, 2007) can be applied in the context of the geological disposal of long-lived solid radioactive waste. Although the report is written as a standalone document, previous ICRP recommendations not dealt with in depth in the report are still valid. The 2007 ICRP system of radiological protection evolves from the previous process-based protection approach relying on the distinction between practices and interventions by moving to an approach based on the distinction between three types of exposure situation: planned, emergency and existing. The Recommendations maintains the Commission's three fundamental principles of radiological protection namely: justification, optimisation of protection and the application of dose limits. They also maintain the current individual dose limits for effective dose and equivalent dose from all regulated sources in planned exposure situations. They re-enforce the principle of optimisation of radiological protection, which applies in a similar way to all exposure situations, subject to restrictions on individual doses: constraints for planned exposure situations, and reference levels for emergency and existing exposure situations. The Recommendations also include an approach for developing a framework to demonstrate radiological protection of the environment. This report describes the different stages in the life time of a geological disposal facility, and addresses the application of relevant radiological protection principles for each stage depending on the various exposure situations that can be encountered. In particular, the crucial factor that influences the application of the protection system over the different phases in the life time of a disposal facility is the level of oversight or 'watchful care' that is present. The level of oversight affects the capability to control the source, i.e. the waste and the repository, and to avoid or reduce potential exposures. Three main time frames are considered: time of direct oversight, when the disposal facility is being implemented and is under active supervision; time of indirect oversight, when the disposal facility is sealed and oversight is being exercised by regulators or special administrative bodies or society at large to provide additional assurance on behalf of society; and time of no oversight, when oversight is no longer exercised in case memory of the disposal facility is lost. Copyright © 2013. Published by Elsevier Ltd.

Organizational effects of the antiandrogen, Vinclozolin, on penis development in the mouse.

PubMed

Amato, Ciro M; Boyd, Morgan; Yang, Joshua; McCoy, Krista A

2018-04-14

Endocrine disrupting chemicals (EDCs) are pollutants found throughout the environment that disrupt normal endocrine processes. In mice, penis development is thought to be most susceptible to EDCs during a critical developmental window occurring on embryonic days (E) 15.5-17.5. However, androgen signaling begins on E13.5 when Androgen Receptor (AR) protein is found in the genitalia and testosterone is circulating. We hypothesize that disrupting androgen signaling prior to the established critical window sensitizes the penis to future androgen disruption. To test this hypothesis, CD1 dams were exposed to Vinclozolin or a corn oil solvent control on E13.5 and E14.5 and AR levels were measured with immunohistochemistry on E14.5. Early antiandrogen exposure reduced AR within nuclei and decreased intensity of AR expression within E14.5 genitalia. To evaluate the influence of antiandrogen exposure before the known critical window of penis development, two groups of pregnant dams (n = 3) were exposed to Vinclozolin starting at either E13.5 or E14.5 and continued exposure through E16.5. Histology and M.O.U.S.E. scoring were used to quantify penis abnormalities. To account for differences in total doses mice experienced due to differences in length of dosing time, we compared animals that received the same total doses. Exposure to antiandrogens on E13.5 exacerbated malformations when exposure was continued through sexually dimorphic development. Both exposure time and Vinclozolin dose are important for severity of Vinclozolin-induced penis abnormalities in mice. This work shows, antiandrogen exposure prior to sensitive periods can exacerbate the effects of later antiandrogen exposure on reproductive development.

Radiological risk assessment of Capstone depleted uranium aerosols.

PubMed

Hahn, Fletcher F; Roszell, Laurie E; Daxon, Eric G; Guilmette, Raymond A; Parkhurst, Mary Ann

2009-03-01

Assessment of the health risk from exposure to aerosols of depleted uranium (DU) is an important outcome of the Capstone aerosol studies that established exposure ranges to personnel in armored combat vehicles perforated by DU munitions. Although the radiation exposure from DU is low, there is concern that DU deposited in the body may increase cancer rates. Radiation doses to various organs of the body resulting from the inhalation of DU aerosols measured in the Capstone studies were calculated using International Commission on Radiological Protection (ICRP) models. Organs and tissues with the highest calculated committed equivalent 50-y doses were lung and extrathoracic tissues (nose and nasal passages, pharynx, larynx, mouth, and thoracic lymph nodes). Doses to the bone surface and kidney were about 5 to 10% of the doses to the extrathoracic tissues. Organ-specific risks were estimated using ICRP and U.S. Environmental Protection Agency (EPA) methodologies. Risks for crewmembers and first responders were determined for selected scenarios based on the time interval of exposure and for vehicle and armor type. The lung was the organ with the highest cancer mortality risk, accounting for about 97% of the risks summed from all organs. The highest mean lifetime risk for lung cancer for the scenario with the longest exposure time interval (2 h) was 0.42%. This risk is low compared with the natural or background risk of 7.35%. These risks can be significantly reduced by using an existing ventilation system (if operable) and by reducing personnel time in the vehicle immediately after perforation.

Nuclear-weapon-effect research at PSR (Pacific-Sierra Research Corporation) - 1983. Volume 10. Symptomatology of acute radiation effects in humans after exposure to doses of 75 to 4500 rads (cGy) free-in-air. Final technical report, 27 October 1982-30 November 1983

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baum, S.J.; Young, R.W.; Anno, G.H.

1984-08-31

This report distills from available data descriptions of typical human symptoms in reaction to prompt ionizing radiation in the dose range 75 to 4500 rads (cGy) free-in-air. The descriptions correlate symptoms with dose and time over the acute post-exposure period of six weeks. Their purpose is to provide an empirical base for estimating combat troop performance after a nuclear weapon attack. The dose range of interest is subdivided into eight subranges associated with important pathophysiological events. For each subrange, the signs and symptoms manifested by an exposed population are estimated--symptom onset, severity, duration, and incidence. The early or prodromal phasemore » of radiation sickness begins about 2 to 4 hrs after doses of 300 to 530 rads (cGy). Onset time diminishes with dose, occurring within minutes of exposure to 4500 rads (cGy). Characteristic prodromal symptoms are nausea, vomiting, anorexia, and diarrhea. The prodromal phase lasts from several days to a matter of hours, depending on dose. Symptoms of the hemopoietic syndrome are bleeding, fever, infection, and ulceration. Symptoms of the gastrointestinal syndrome are fluid loss, electrolyte imbalance, severe diarrhea, and septicemia.« less

Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India: Recommendations for Dose Modifications.

PubMed

Guiastrennec, Benjamin; Ramachandran, Geetha; Karlsson, Mats O; Kumar, A K Hemanth; Bhavani, Perumal Kannabiran; Gangadevi, N Poorana; Swaminathan, Soumya; Gupta, Amita; Dooley, Kelly E; Savic, Radojka M

2017-12-16

This work aimed to evaluate the once-daily antituberculosis treatment as recommended by the new Indian pediatric guidelines. Isoniazid, rifampin, and pyrazinamide concentration-time profiles and treatment outcome were obtained from 161 Indian children with drug-sensitive tuberculosis undergoing thrice-weekly dosing as per previous Indian pediatric guidelines. The exposure-response relationships were established using a population pharmacokinetic-pharmacodynamic approach. Rifampin exposure was identified as the unique predictor of treatment outcome. Consequently, children with low body weight (4-7 kg) and/or HIV infection, who displayed the lowest rifampin exposure, were associated with the highest probability of unfavorable treatment (therapy failure, death) outcome (P unfavorable ). Model-based simulation of optimized (P unfavorable ≤ 5%) rifampin once-daily doses were suggested per treatment weight band and HIV coinfection status (33% and 190% dose increase, respectively, from the new Indian guidelines). The established dose-exposure-response relationship could be pivotal in the development of future pediatric tuberculosis treatment guidelines. © 2017, The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

The effect of exposure duration on the subjective discomfort of aircraft cabin noise.

PubMed

Huang, Yu; Jiang, Weikang

2017-01-01

The time dependency for subjective responses to noise has been a controversial question over many years. For durations of up to 10 min, the discomfort produced by three levels of noise (ie 60, 70 and 80 dBA) was investigated in this experimental study to determine the relation of discomfort to the time duration of noise. The rate of increase in discomfort with increasing duration was 1.5 dB per doubling of exposure duration, whereas it is currently assumed to be 3 dB per doubling of exposure duration. The sound dose level (SDL) was proposed to predict the discomfort caused by noise of long duration. The combination of SDL and vibration dose value (VDV) provided more consistent estimates of the equivalent comfort contours between noise and vibration over durations from 2 to 32 s than the combination of sound exposure level and VDV or that of sound pressure level and r.m.s. acceleration. Practitioner Summary: The discomfort produced by noise of long duration can be well predicted from a new definition of sound dose level, where the discomfort increases at 1.5 dB per doubling of exposure duration.

Gene expression-based dosimetry by dose and time in mice following acute radiation exposure.

PubMed

Tucker, James D; Divine, George W; Grever, William E; Thomas, Robert A; Joiner, Michael C; Smolinski, Joseph M; Auner, Gregory W

2013-01-01

Rapid and reliable methods for performing biological dosimetry are of paramount importance in the event of a large-scale nuclear event. Traditional dosimetry approaches lack the requisite rapid assessment capability, ease of use, portability and low cost, which are factors needed for triaging a large number of victims. Here we describe the results of experiments in which mice were acutely exposed to (60)Co gamma rays at doses of 0 (control) to 10 Gy. Blood was obtained from irradiated mice 0.5, 1, 2, 3, 5, and 7 days after exposure. mRNA expression levels of 106 selected genes were obtained by reverse-transcription real time PCR. Stepwise regression of dose received against individual gene transcript expression levels provided optimal dosimetry at each time point. The results indicate that only 4-7 different gene transcripts are needed to explain ≥ 0.69 of the variance (R(2)), and that receiver-operator characteristics, a measure of sensitivity and specificity, of ≥ 0.93 for these statistical models were achieved at each time point. These models provide an excellent description of the relationship between the actual and predicted doses up to 6 Gy. At doses of 8 and 10 Gy there appears to be saturation of the radiation-response signals with a corresponding diminution of accuracy. These results suggest that similar analyses in humans may be advantageous for use in a field-portable device designed to assess exposures in mass casualty situations.

Effect of continuous gamma-ray exposure on performance of learned tasks and effect of subsequent fractionated exposures on blood-forming tissue

NASA Technical Reports Server (NTRS)

Spalding, J. F.; Holland, L. M.; Prine, J. R.; Farrer, D. N.; Braun, R. G.

1972-01-01

Sixteen monkeys trained to perform continuous and discrete-avoidance and fixed-ratio tasks with visual and auditory cues were performance-tested before, during, and after 10-day gamma-ray exposures totaling 0, 500, 750, and 1000 rads. Approximately 14 months after the performance-test exposures, surviving animals were exposed to 100-rad gamma-ray fractions at 56-day intervals to observe injury and recovery patterns of blood-forming tissues. The fixed-ratio, food-reward task performance showed a transient decline in all dose groups within 24 hours of the start of gamma-ray exposure, followed by recovery to normal food-consumption levels within 48 to 72 hours. Avoidance tasks were performed successfully by all groups during the 10-day exposure, but reaction times of the two higher dose-rate groups in which animals received 3 and 4 rads per hour or total doses of 750 and 1000 rads, respectively, were somewhat slower.

Dose-response patterns for vibration-induced white finger

PubMed Central

Griffin, M; Bovenzi, M; Nelson, C

2003-01-01

Aims: To investigate alternative relations between cumulative exposures to hand-transmitted vibration (taking account of vibration magnitude, lifetime exposure duration, and frequency of vibration) and the development of white finger (Raynaud's phenomenon). Methods: Three previous studies have been combined to provide a group of 1557 users of powered vibratory tools in seven occupational subgroups: stone grinders, stone carvers, quarry drillers, dockyard caulkers, dockyard boilermakers, dockyard painters, and forest workers. The estimated total operating duration in hours was thus obtained for each subject, for each tool, and for all tools combined. From the vibration magnitudes and exposure durations, seven alternative measurements of cumulative exposure were calculated for each subject, using expressions of the form: dose = ∑amiti, where ai is the acceleration magnitude on tool i, ti is the lifetime exposure duration for tool i, and m = 0, 1, 2, or 4. Results: For all seven alternative dose measures, an increase in dose was associated with a significant increase in the occurrence of vibration-induced white finger, after adjustment for age and smoking. However, dose measures with high powers of acceleration (m > 1) faired less well than measures in which the weighted or unweighted acceleration, and lifetime exposure duration, were given equal weight (m = 1). Dose determined solely by the lifetime exposure duration (without consideration of the vibration magnitude) gave better predictions than measures with m greater than unity. All measures of dose calculated from the unweighted acceleration gave better predictions than the equivalent dose measures using acceleration frequency-weighted according to current standards. Conclusions: Since the total duration of exposure does not discriminate between exposures accumulated over the day and those accumulated over years, a linear relation between vibration magnitude and exposure duration seems appropriate for predicting the occurrence of vibration-induced white finger. Poorer predictions were obtained when the currently recommended frequency weighting was employed than when accelerations at all frequencies were given equal weight. Findings suggest that improvements are possible to both the frequency weighting and the time dependency used to predict the development of vibration-induced white finger in current standards. PMID:12499452

In-Situ Strain Analysis of Potential Habitat Composites Exposed to a Simulated Long-Term Lunar Radiation Exposure

NASA Technical Reports Server (NTRS)

Rojdev, Kristina; O'Rourke, Mary Jane; Hill, Charles; Nutt, Steven; Atwell, William

2010-01-01

NASA is studying the effects of long-term space radiation on potential multifunctional composite materials for habitats to better determine their characteristics in the harsh space environment. Two composite materials were selected for the study and were placed in a test stand that simulated the stresses of a pressure vessel wall on the material. The samples in the test stand were exposed to radiation at either a fast dose rate or a slow dose rate, and their strain and temperature was recorded during the exposure. It was found that during a fast dose rate exposure the materials saw a decreased strain with time, or a shrinking of the materials. Given previous radiation studies of polymers, this is believed to be a result of crosslinking occurring in the matrix material. However, with a slow dose rate, the materials saw an increase in strain with time, or a stretching of the materials. This result is consistent with scission or degradation of the matrix occurring, possibly due to oxidative degradation.

[Examination of patient dose reduction in cardiovasucular X-ray systems with a metal filter].

PubMed

Yasuda, Mitsuyoshi; Kato, Kyouichi; Tanabe, Nobuaki; Sakiyama, Koushi; Uchiyama, Yushi; Suzuki, Yoshiaki; Suzuki, Hiroshi; Nakazawa, Yasuo

2012-01-01

In interventional X-ray for cardiology of flat panel digital detector (FPD), the phenomenon that exposure dose was suddenly increased when a subject thickness was thickened was recognized. At that time, variable metal built-in filters in FPD were all off. Therefore, we examined whether dose reduction was possible without affecting a clinical image using metal filter (filter) which we have been conventionally using for dose reduction. About 45% dose reduction was achieved when we measured an exposure dose at 30 cm of acrylic thickness in the presence of a filter. In addition, we measured signal to noise ratio/contrast to noise ratio/a resolution limit by the visual evaluation, and there was no influence by filter usage. In the clinical examination, visual evaluation of image quality of coronary angiography (40 cases) using a 5-point evaluation scale by a physician was performed. As a result, filter usage did not influence the image quality (p=NS). Therefore, reduction of sudden increase of exposure dose was achieved without influencing an image quality by adding filter to FPD.

Assessing the performance of the generalized propensity score for estimating the effect of quantitative or continuous exposures on survival or time-to-event outcomes.

PubMed

Austin, Peter C

2018-01-01

Propensity score methods are frequently used to estimate the effects of interventions using observational data. The propensity score was originally developed for use with binary exposures. The generalized propensity score (GPS) is an extension of the propensity score for use with quantitative or continuous exposures (e.g. pack-years of cigarettes smoked, dose of medication, or years of education). We describe how the GPS can be used to estimate the effect of continuous exposures on survival or time-to-event outcomes. To do so we modified the concept of the dose-response function for use with time-to-event outcomes. We used Monte Carlo simulations to examine the performance of different methods of using the GPS to estimate the effect of quantitative exposures on survival or time-to-event outcomes. We examined covariate adjustment using the GPS and weighting using weights based on the inverse of the GPS. The use of methods based on the GPS was compared with the use of conventional G-computation and weighted G-computation. Conventional G-computation resulted in estimates of the dose-response function that displayed the lowest bias and the lowest variability. Amongst the two GPS-based methods, covariate adjustment using the GPS tended to have the better performance. We illustrate the application of these methods by estimating the effect of average neighbourhood income on the probability of survival following hospitalization for an acute myocardial infarction.

Assessment of the point-source method for estimating dose rates to members of the public from exposure to patients with 131I thyroid treatment

DOE PAGES

Dewji, Shaheen Azim; Bellamy, Michael B.; Hertel, Nolan E.; ...

2015-09-01

The U.S. Nuclear Regulatory Commission (USNRC) initiated a contract with Oak Ridge National Laboratory (ORNL) to calculate radiation dose rates to members of the public that may result from exposure to patients recently administered iodine-131 ( 131I) as part of medical therapy. The main purpose was to compare dose rate estimates based on a point source and target with values derived from more realistic simulations that considered the time-dependent distribution of 131I in the patient and attenuation of emitted photons by the patient’s tissues. The external dose rate estimates were derived using Monte Carlo methods and two representations of themore » Phantom with Movable Arms and Legs, previously developed by ORNL and the USNRC, to model the patient and a nearby member of the public. Dose rates to tissues and effective dose rates were calculated for distances ranging from 10 to 300 cm between the phantoms and compared to estimates based on the point-source method, as well as to results of previous studies that estimated exposure from 131I patients. The point-source method overestimates dose rates to members of the public in very close proximity to an 131I patient but is a broadly accurate method of dose rate estimation at separation distances of 300 cm or more at times closer to administration.« less

Lymphatic involution and early mortality in the young chicken produced by 2.2 GeV protons

NASA Technical Reports Server (NTRS)

Montour, J. L.; Shellabarger, C. J.

1972-01-01

Young single-comb white Leghorn cockerels were subjected to single acute doses of either 2.2 GeV protons or 250 kVp X-rays. Since young chickens exposed in the lethal range die within 48 hours of exposure, an hourly tabulation of deaths was recorded for this length of time after exposure. Animals which were exposed to sublethal doses were killed five days after exposure and their major lymphatic organs, (thymus, bursa, and spleen), removed and weighed. In the lethal range, animals exposed to 2.2 GeV protons died sooner than those receiving similar doses of X-rays, but total mortality was similar in each case at similar dose levels. The 48 hour LD sub 50 was determined to be 710 rad. Measured five days after exposure, 50% depression ED sub 50 for lymphatic organs occurred as follows: (1) thymus, 350 rad; (2) pursa, 500 rad, and (3) spleen, 450 rad. In all case R.B.E. values were not different from unity.

Risk of breast cancer following low-dose radiation exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boice, J.D. Jr.; Land, C.E.; Shore, R.E.

1979-06-01

Risk of breast cancer following radiation exposure was studied, based on surveys of tuberculosis patients who had multiple fluoroscopic examinations of the chest, mastitis patients given radiotherapy, and atomic bomb survivors. Analysis suggests that the risk is greatest for persons exposed as adolescents, although exposure at all ages carries some risk. The dose-response relationship was consistent with linearity in all studies. Direct evidence of radiation risk at doses under 0.5 Gy (50 rad) is apparent among A-bomb survivors. Fractionation does not appear to diminish risk, nor does time since exposure (even after 45 years of observation). The interval between exposuremore » and the clinical appearance of radiogenic breast cancer may be mediated by hormonal or other age-related factors but is unrelated to dose. Age-specific absolute risk estimtes for all studies are remarkably similar. The best estimate of risk among American women exposed after age 20 is 6.6 excess cancers/10/sup 4/ WY-Gy (10/sup 6/ WY-rad).« less

Radiation exposure during in-situ pinning of slipped capital femoral epiphysis hips: does the patient positioning matter?

PubMed

Mohammed, Riazuddin; Johnson, Karl; Bache, Ed

2010-07-01

Multiple radiographic images may be necessary during the standard procedure of in-situ pinning of slipped capital femoral epiphysis (SCFE) hips. This procedure can be performed with the patient positioned on a fracture table or a radiolucent table. Our study aims to look at any differences in the amount and duration of radiation exposure for in-situ pinning of SCFE performed using a traction table or a radiolucent table. Sixteen hips in thirteen patients who were pinned on radiolucent table were compared for the cumulative radiation exposure to 35 hips pinned on a fracture table in 33 patients during the same time period. Cumulative radiation dose was measured as dose area product in Gray centimeter2 and the duration of exposure was measured in minutes. Appropriate statistical tests were used to test the significance of any differences. Mean cumulative radiation dose for SCFE pinned on radiolucent table was statistically less than for those pinned on fracture table (P<0.05). The mean duration of radiation exposure on either table was not significantly different. Lateral projections may increase the radiation doses compared with anteroposterior projections because of the higher exposure parameters needed for side imaging. Our results showing decreased exposure doses on the radiolucent table are probably because of the ease of a frog leg lateral positioning obtained and thereby the ease of lateral imaging. In-situ pinning of SCFE hips on a radiolucent table has an additional advantage that the radiation dose during the procedure is significantly less than that of the procedure that is performed on a fracture table.

AN "INJURY-TIME INTEGRAL" MODEL FOR RELATING ACUTE TO CHRONIC INJURY TO PHOSGENE

EPA Science Inventory

ABSTRACT
The present study compares acute and subchronic episodic exposures to phosgene to test the applicability of the "concentration x time" (C x T) product as a measure of exposure dose, and to relate acute toxicity and adaptive responses to chronic toxicity. Rats (m...

Vulnerability of the neural circuitry underlying sexual behavior to chronic adult exposure to oral bisphenol a in male mice.

PubMed

Picot, Marie; Naulé, Lydie; Marie-Luce, Clarisse; Martini, Mariangela; Raskin, Kalina; Grange-Messent, Valérie; Franceschini, Isabelle; Keller, Matthieu; Mhaouty-Kodja, Sakina

2014-02-01

There are human reproduction concerns associated with extensive use of bisphenol A (BPA)-containing plastic and, in particular, the leaching of BPA into food and beverages. In this context, it remains unclear whether and how exposure to BPA interferes with the developmental organization and adult activation of male sexual behavior by testosterone. We evaluated the developmental and adult exposure to oral BPA at doses equivalent to the no-observed-adverse-effect-level (5 mg/kg body weight per day) and tolerable daily intake (TDI) (50 μg/kg body weight per day) on mouse sexual behavior and the potential mechanisms underlying BPA effects. Adult exposure to BPA reduced sexual motivation and performance at TDI dose only. Exposed males took longer to initiate mating and reach ejaculation despite normal olfactory chemoinvestigation. This deficiency was not restored by sexual experience and was associated with unchanged circulating levels of testosterone. By contrast, developmental exposure to BPA at TDI or no-observed-adverse-effect-level dose did not reduce sexual behavior or alter the neuroanatomical organization of the preoptic area. Disrupting the neural androgen receptor resulted in behavioral and neuroanatomical effects similar to those induced by adult exposure to TDI dose. Moreover, adult exposure of mutant males to BPA at TDI dose did not trigger additional alteration of sexual behavior, suggesting that BPA and neural androgen receptor mutation share a common mechanism of action. This shows, for the first time, that the neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA and suggests that BPA could act in vivo as an antiandrogenic compound.

Personal radiofrequency electromagnetic field exposure measurements in Swiss adolescents.

PubMed

Roser, Katharina; Schoeni, Anna; Struchen, Benjamin; Zahner, Marco; Eeftens, Marloes; Fröhlich, Jürg; Röösli, Martin

2017-02-01

Adolescents belong to the heaviest users of wireless communication devices, but little is known about their personal exposure to radiofrequency electromagnetic fields (RF-EMF). The aim of this paper is to describe personal RF-EMF exposure of Swiss adolescents and evaluate exposure relevant factors. Furthermore, personal measurements were used to estimate average contributions of various sources to the total absorbed RF-EMF dose of the brain and the whole body. Personal exposure was measured using a portable RF-EMF measurement device (ExpoM-RF) measuring 13 frequency bands ranging from 470 to 3600MHz. The participants carried the device for three consecutive days and kept a time-activity diary. In total, 90 adolescents aged 13 to 17years participated in the study conducted between May 2013 and April 2014. In addition, personal measurement values were combined with dose calculations for the use of wireless communication devices to quantify the contribution of various RF-EMF sources to the daily RF-EMF dose of adolescents. Main contributors to the total personal RF-EMF measurements of 63.2μW/m 2 (0.15V/m) were exposures from mobile phones (67.2%) and from mobile phone base stations (19.8%). WLAN at school and at home had little impact on the personal measurements (WLAN accounted for 3.5% of total personal measurements). According to the dose calculations, exposure from environmental sources (broadcast transmitters, mobile phone base stations, cordless phone base stations, WLAN access points, and mobile phones in the surroundings) contributed on average 6.0% to the brain dose and 9.0% to the whole-body dose. RF-EMF exposure of adolescents is dominated by their own mobile phone use. Environmental sources such as mobile phone base stations play a minor role. Copyright © 2016 Elsevier Ltd. All rights reserved.

The maximal cumulative solar UVB dose allowed to maintain healthy and young skin and prevent premature photoaging.

PubMed

Ichihashi, Masamitsu; Ando, Hideya

2014-10-01

The young facial skin of children with a smooth healthy appearance changes over time to photoaged skin having mottled pigmentation, solar lentigines, wrinkles, dry and rough skin, leathery texture, and benign and malignant tumors after exposure to chronic, repeated solar radiation. The first sign of photoaging in Japanese subjects is usually solar lentigines appearing around 20 years of age on the face. Fine wrinkles can then appear after 30 years of age, and benign skin tumors, seborrhoeic keratoses, can occur after 35 years of age in sun-exposed skin. We theoretically calculated the maximal daily exposure time to solar radiation, which could prevent the development of photoaged skin until 60 and 80 years of age, based on published data of personal solar UVB doses in sun-exposed skin. One MED (minimal erythema dose) was determined to be 20 mJ/cm(2) , and 200 MED was used as the average yearly dose of Japanese children. Further, we hypothesized that the annual dose of Japanese adults is the same as that of the children. The cumulative UVB dose at 20 years of age was thus calculated to be 4000 MED, and 22 MED was used as the maximal daily UVB dose based on data measured in Kobe, located in the central area of Japan. We used the solar UVB dose from 10:00 a.m. to 14:00 p.m. which occupies 60% of the total daily UV dose, to obtain the maximal UVB per hour in a day, and calculated the maximal daily UV exposure time that would delay the onset of solar lentigines until 60 or 80 years of age. The mean daily sun exposure time to maintain healthy skin until 80 years of age in the summer was calculated to be 2.54 min (0.14 MED) for unprotected skin and 127 min with the use of a sunscreen of SPF (sun protection factor) of 50. In this study, we did not evaluate the photoaging effect of UVA radiation, but findings of the adverse effects of UVA radiation on the skin have accumulated in the last decade. Therefore, it will be important to estimate the maximal dose of solar UV radiation to retard the onset of photoaging based on an evaluation of both solar UVB and UVA in the future. Finally, we expect that this study may contribute to keeping Japanese and other types of skin young and healthy by limiting the exposure of the skin to solar radiation outdoors during the day. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Using serology to assist with complicated post-exposure prophylaxis for rabies and Australian bat lyssavirus.

PubMed

Conroy, Niall; Vlack, Susan; Williams, Julian M; Patten, John J; Horvath, Robert L; Lambert, Stephen B

2013-01-01

Australia uses a protocol combining human rabies immunoglobulin (HRIG) and rabies vaccine for post-exposure prophylaxis (PEP) of rabies and Australian bat lyssavirus (ABLV), with the aim of achieving an antibody titre of ≥0.5 IU/ml, as per World Health Organization (WHO) guidelines, as soon as possible. We present the course of PEP administration and serological testing for four men with complex requirements. Following dog bites in Thailand, two men (62 years old, 25 years old) received no HRIG and had delayed vaccine courses: 23 days between dose two and three, and 18 days between dose one and two, respectively. Both seroconverted following dose four. Another 62-year-old male, who was HIV-positive (normal CD4 count), also suffered a dog bite and had delayed care receiving i.m. rabies vaccine on days six and nine in Thailand. Back in Australia, he received three single and one double dose i.m. vaccines followed by another double dose of vaccine, delivered intradermally and subcutaneously, before seroconverting. A 23-year-old male with a history of allergies received simultaneous HRIG and vaccine following potential ABLV exposure, and developed rash, facial oedema and throat tingling, which was treated with a parenteral antihistamine and tapering dose of steroids. Serology showed he seroconverted following dose four. These cases show that PEP can be complicated by exposures in tourist settings where reliable prophylaxis may not be available, where treatment is delayed or deviates from World Health Organization recommendations. Due to the potentially short incubation time of rabies/ABLV, timely prophylaxis after a potential exposure is needed to ensure a prompt and adequate immune response, particularly in patients who are immune-suppressed or who have not received HRIG. Serology should be used to confirm an adequate response to PEP when treatment is delayed or where a concurrent immunosuppressing medical condition or therapy exists.

[Estimation of effective doses derived from radon in selected SPA centers that use geothermal waters based on the information of radon concentrations].

PubMed

Walczak, Katarzyna; Zmyślony, Marek

2013-01-01

Geothermal waters contain, among other components, soluble radon gas. Alpha radioactive radon is a health hazard to humans, especially when it gets into the respiratory tract. SPA facilities that use geothermal water can be a source of an increased radiation dose to people who stay there. Based on the available literature concerning radon concentrations, we assessed exposure to radon among people - workers and visitors of Spa centers that use geothermal waters. Radon concentrations were analyzed in 17 geothermal centers: in Greece (3 centers), Iran (5), China (4) and India (5). Doses recived by people in the SPA were estimated using the formula that 1 hour exposure to 1 Bq/m3 of radon concentration and equilibrium factor F = 0.4 corresponds to an effective dose of 3.2 nSv. We have found that radon levels in SPAs are from a few to several times higher than those in confined spaces, where geothermal waters are not used (e.g., residential buildings). In 82% of the analyzed SPAs, workers may receive doses above 1 mSv/year. According to the relevant Polish regulations, people receiving doses higher than 1 mSv/year are included in category B of radiation exposure and require regular dosimetric monitoring. Doses received by SPA visitors are much lower because the time of their exposure to radon released from geothermal water is rather short. The analysis of radon concentration in SPA facilities shows that the radiological protection of people working with geothermal waters plays an important role. It seems reasonable to include SPA workers staying close to geotermal waters into a dosimetric monitoring program.

Balance between early life tolerance and sensitization in allergy: dependence on the timing and intensity of prenatal and postnatal allergen exposure of the mother.

PubMed

Fusaro, Ana Elisa; de Brito, Cyro Alves; Taniguchi, Eliana Futata; Muniz, Bruno Pacola; Victor, Jefferson Russo; Orii, Noemia Mie; Duarte, Alberto José da Silva; Sato, Maria Notomi

2009-09-01

Allergens can be maternally transferred to the fetus or neonate, though it is uncertain how this initial allergen exposure may impact the development of allergy responses. To evaluate the roles of timing and level of maternal allergen exposure in the early life sensitization of progeny, female BALB/c mice were given ovalbumin (OVA) orally during pregnancy, lactation or weekly at each stage to investigate the immunoglobulin E (IgE) antibody production and cellular responsiveness of their offspring. Exposure to OVA during pregnancy was also evaluated in OVA-specific T-cell receptor (TCR) transgenic (DO11.10) mice. The effect of prenatal antigen exposure on offspring sensitization was dependent on antigen intake, with low-dose OVA inducing tolerance followed by neonatal immunization that was sustained even when pups were immunized when 3 weeks old. These offspring received high levels of transforming growth factor-beta via breastfeeding. High-dose exposure during the first week of pregnancy or perinatal period induced transient inhibition of IgE production following neonatal immunization; although for later immunization IgE production was enhanced in these offspring. Postnatal maternal antigen exposure provided OVA transference via breastfeeding, which consequently induced increased offspring susceptibility to IgE antibody production according to week post-birth. The effect of low-dose maternal exposure during pregnancy was further evaluated using OVA transgenic TCR dams as a model. These progeny presented pronounced entry of CD4(+) T cells into the S phase of the cell cycle with a skewed T helper type 2 response early in life, revealing the occurrence of allergen priming in utero. The balance between tolerance and sensitization depended on the amount and timing of maternal allergen intake during pregnancy.

Endovascular aortic sealing with Nellix reduces intraoperative radiation dose when compared to endovascular aortic repair.

PubMed

Ockert, Stefan; Heinrich, Mirjam; Kaufmann, Thomas; Syburra, Thomas; Lopez, Ruben; Seelos, Robert

2018-04-01

To analyze radiation exposure during endovascular aortic sealing (EVAS) in comparison with standard endovascular aortic repair (EVAR) in clinical practice. From December 2013 to October 2016 (35 months), 60 patients were analyzed for intraoperative radiation exposure during EVAR: 30 consecutive patients (mean age, 73.10 years; 28 male) received EVAS (Nellix Endologix); within the same time frame, 30 patients were treated with standard EVAR (mean age, 71.87 years; 30 male). An indirect dose analysis was performed for both groups of patients, including effective dose and cumulative air kerma. Furthermore, fluoroscopy time (FT), dose area product, and time of procedure were included in the study. The effective dose was significantly reduced in the EVAS group (3.72 mSv) compared with the group treated with standard EVAR (6.8 mSv; P ≤ .001). The cumulative air kerma was also lowered in EVAS (67.65 mGy vs 139 mGy in EVAR; P ≤ .001). FT for the entire group was 13 minutes and was shorter (P < .001) for EVAS (9 minutes) in comparison with EVAR (19 minutes). The dose area product for the entire cohort was 16.95 Gy.cm 2 and was lower during EVAS (12.4 Gy.cm 2 ) than during EVAR (22.6 Gy.cm 2 ; P < .001). The median operating time for the entire group was 123.5 minutes and was significantly shorter (P < .01) for EVAS (119 minutes vs EVAR at 132 minutes). The FT shows a significant correlation with the patient's weight (P = .022), body mass index (P = .004), and time of procedure (P = .005). EVAS is associated with a relevant decrease in indirect measured radiation dose and time of procedure compared with standard EVAR. A relevant reduction in dose during EVAS is highly likely to result in lower exposure to radiation for physicians and staff. Such a result would be highly advantageous and calls for further analysis. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The margin of internal exposure (MOIE) concept for dermal risk assessment based on oral toxicity data - A case study with caffeine.

PubMed

Bessems, Jos G M; Paini, Alicia; Gajewska, Monika; Worth, Andrew

2017-12-01

Route-to-route extrapolation is a common part of human risk assessment. Data from oral animal toxicity studies are commonly used to assess the safety of various but specific human dermal exposure scenarios. Using theoretical examples of various user scenarios, it was concluded that delineation of a generally applicable human dermal limit value is not a practicable approach, due to the wide variety of possible human exposure scenarios, including its consequences for internal exposure. This paper uses physiologically based kinetic (PBK) modelling approaches to predict animal as well as human internal exposure dose metrics and for the first time, introduces the concept of Margin of Internal Exposure (MOIE) based on these internal dose metrics. Caffeine was chosen to illustrate this approach. It is a substance that is often found in cosmetics and for which oral repeated dose toxicity data were available. A rat PBK model was constructed in order to convert the oral NOAEL to rat internal exposure dose metrics, i.e. the area under the curve (AUC) and the maximum concentration (C max ), both in plasma. A human oral PBK model was constructed and calibrated using human volunteer data and adapted to accommodate dermal absorption following human dermal exposure. Use of the MOIE approach based on internal dose metrics predictions provides excellent opportunities to investigate the consequences of variations in human dermal exposure scenarios. It can accommodate within-day variation in plasma concentrations and is scientifically more robust than assuming just an exposure in mg/kg bw/day. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Implications of sequence and timing of exposure for synergy between the pyrethroid insecticide alpha-cypermethrin and the entomopathogenic fungus Beauveria bassiana.

PubMed

Meyling, Nicolai V; Arthur, Samuel; Pedersen, Kathrine E; Dhakal, Suraj; Cedergreen, Nina; Fredensborg, Brian L

2018-03-30

Combining low doses of chemical insecticides with entomopathogens constitutes a sustainable pest control method, but the significance of the timing and sequence of exposures needs clarification. We studied lethal effects of combinations of the entomopathogenic fungus Beauveria bassiana (KVL03-122) and the pyrethroid alpha-cypermethrin on the beetle Tenebrio molitor under varying timing and sequence of exposure. Synergy over time was evaluated in relation to the model of independent action (IA). We expected that increased progression of disease caused by B. bassiana would make beetles more susceptible to the insecticide, leading to enhanced synergy. Synergistic effects between B. bassiana and alpha-cypermethrin were observed when B. bassiana was applied first, but only when the interval between applications was >48 h. With 72 h between exposures, mortality had increased to 100% after 8 days, in contrast to the 60% mortality expected. No synergy was observed when the insecticide was applied prior to fungal exposure within 24 h. The sequence and timing of exposure do matter to achieve synergistic mortality by combining B. bassiana and alpha-cypermethrin, and the IA model proved to be a strong tool with which to evaluate the interactions of the two stressors over time. Pest control strategies could include B. bassiana followed by low-dose exposures to alpha-cypermethrin after 2-3 days. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Preliminary results on the photo-transferred thermoluminescence from Ge-doped SiO2 optical fiber

NASA Astrophysics Data System (ADS)

Zulkepely, Nurul Najua; Amin, Yusoff Mohd; Md Nor, Roslan; Bradley, D. A.; Maah, Mohd Jamil; Mat Nawi, Siti Nurasiah; Wahib, Nur Fadira

2015-12-01

A study is made of photo-transferred thermoluminescence (PTTL), the TL being induced by transferring charge carriers from deeper to more superficial traps through energetic light exposure. Potential applications include dose reassessment in radiation dosimetry and also as a useful tool for dating. With incomplete emptying of deep traps following first readout, subsequent UV exposure is shown to lead to charge transfer to more shallow traps. Using Ge-doped SiO2 optical fibers exposed to 60Co gamma rays, the PTTL from the medium has been characterized in terms of the stimulation provided by exposure to a UV lamp and duration of exposure, maximum read-out temperature and pre-gamma irradiation dose. Ge-doped SiO2 optical fibers of flat cross-sectional shape have been used in this study. The efficiency of dose reassessment was compared to that of the highly popular phosphor-based TL detector TLD-100. Results show the maximum temperature of readout to have no measurable effect on the PTTL signal. For doses from 20 to 500 cGy, the method is shown to be effective using a UV lamp of wavelength 254 nm, also being indicative of potential application for doses on either side of the range currently investigated. A study was also made of the effect of UV exposure time on PTTL, seeking to determine the greatest accessible sensitivity and lowest measurable dose.

Methodologies for the quantitative estimation of toxicant dose to cigarette smokers using physical, chemical and bioanalytical data.

PubMed

St Charles, Frank Kelley; McAughey, John; Shepperd, Christopher J

2013-06-01

Methodologies have been developed, described and demonstrated that convert mouth exposure estimates of cigarette smoke constituents to dose by accounting for smoke spilled from the mouth prior to inhalation (mouth-spill (MS)) and the respiratory retention (RR) during the inhalation cycle. The methodologies are applicable to just about any chemical compound in cigarette smoke that can be measured analytically and can be used with ambulatory population studies. Conversion of exposure to dose improves the relevancy for risk assessment paradigms. Except for urinary nicotine plus metabolites, biomarkers generally do not provide quantitative exposure or dose estimates. In addition, many smoke constituents have no reliable biomarkers. We describe methods to estimate the RR of chemical compounds in smoke based on their vapor pressure (VP) and to estimate the MS for a given subject. Data from two clinical studies were used to demonstrate dose estimation for 13 compounds, of which only 3 have urinary biomarkers. Compounds with VP > 10(-5) Pa generally have RRs of 88% or greater, which do not vary appreciably with inhalation volume (IV). Compounds with VP < 10(-7) Pa generally have RRs dependent on IV and lung exposure time. For MS, mean subject values from both studies were slightly greater than 30%. For constituents with urinary biomarkers, correlations with the calculated dose were significantly improved over correlations with mouth exposure. Of toxicological importance is that the dose correlations provide an estimate of the metabolic conversion of a constituent to its respective biomarker.

Residential Exposure to Natural Background Radiation and Risk of Childhood Acute Leukemia in France, 1990–2009

PubMed Central

Demoury, Claire; Marquant, Fabienne; Ielsch, Géraldine; Goujon, Stéphanie; Debayle, Christophe; Faure, Laure; Coste, Astrid; Laurent, Olivier; Guillevic, Jérôme; Laurier, Dominique; Hémon, Denis; Clavel, Jacqueline

2016-01-01

Background: Exposures to high-dose ionizing radiation and high-dose rate ionizing radiation are established risk factors for childhood acute leukemia (AL). The risk of AL following exposure to lower doses due to natural background radiation (NBR) has yet to be conclusively determined. Methods: AL cases diagnosed over 1990–2009 (9,056 cases) were identified and their municipality of residence at diagnosis collected by the National Registry of Childhood Cancers. The Geocap study, which included the 2,763 cases in 2002–2007 and 30,000 population controls, was used for complementary analyses. NBR exposures were modeled on a fine scale (36,326 municipalities) based on measurement campaigns and geological data. The power to detect an association between AL and dose to the red bone marrow (RBM) fitting UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) predictions was 92%, 45% and 99% for exposure to natural gamma radiation, radon and total radiation, respectively. Results: AL risk, irrespective of subtype and age group, was not associated with the exposure of municipalities to radon or gamma radiation in terms of yearly exposure at age reached, cumulative exposure or RBM dose. There was no confounding effect of census-based socio-demographic indicators, or environmental factors (road traffic, high voltage power lines, vicinity of nuclear plants) related to AL in the Geocap study. Conclusions: Our findings do not support the hypothesis that residential exposure to NBR increases the risk of AL, despite the large size of the study, fine scale exposure estimates and wide range of exposures over France. However, our results at the time of diagnosis do not rule out a slight association with gamma radiation at the time of birth, which would be more in line with the recent findings in the UK and Switzerland. Citation: Demoury C, Marquant F, Ielsch G, Goujon S, Debayle C, Faure L, Coste A, Laurent O, Guillevic J, Laurier D, Hémon D, Clavel J. 2017. Residential exposure to natural background radiation and risk of childhood acute leukemia in France, 1990–2009. Environ Health Perspect 125:714–720; http://dx.doi.org/10.1289/EHP296 PMID:27483500

Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study.

PubMed

Tsubokura, Masaharu; Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

2017-01-01

After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)-4.29 mSv), 0.37 mSv (range: ND-3.61 mSv), 0.22 mSv (range: ND-1.44 mSv), 0.20 mSv (range: ND-1.87 mSv), and 0.17 mSv (range: ND-0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04-0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and temporal effects on reducing individual external doses.

Mechanisms of Low Dose Radiation-induced T helper Cell Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gridley, Daila S.

Exposure to radiation above levels normally encountered on Earth can occur during wartime, accidents such as those at Three Mile Island and Chernobyl, and detonation of “dirty bombs” by terrorists. Relatively high levels of radiation exposure can also occur in certain occupations (low-level waste sites, nuclear power plants, nuclear medicine facilities, airline industry, and space agencies). Depression or dysfunction of the highly radiosensitive cells of the immune system can lead to serious consequences, including increased risk for infections, cancer, hypersensitivity reactions, poor wound healing, and other pathologies. The focus of this research was on the T helper (Th) subset ofmore » lymphocytes that secrete cytokines (proteins), and thus control many actions and interactions of other cell types that make up what is collectively known as the immune system. The Department of Energy (DOE) Low Dose Radiation Program is concerned with mechanisms altered by exposure to high energy photons (x- and gamma-rays), protons and electrons. This study compared, for the first time, the low-dose effects of two of these radiation forms, photons and protons, on the response of Th cells, as well as other cell types with which they communicate. The research provided insights regarding gene expression patterns and capacity to secrete potent immunostimulatory and immunosuppressive cytokines, some of which are implicated in pathophysiological processes. Furthermore, the photon versus proton comparison was important not only to healthy individuals who may be exposed, but also to patients undergoing radiotherapy, since many medical centers in the United States, as well as worldwide, are now building proton accelerators. The overall hypothesis of this study was that whole-body exposure to low-dose photons (gamma-rays) will alter CD4+ Th cell function. We further proposed that exposure to low-dose proton radiation will induce a different pattern of gene and functional changes compared to photons. Over the course of this research, tissues other than spleens were archived and with funding obtained from other sources, including the Department of Radiation Medicine at the Loma Linda University Medical Center, some additional assays were performed. Furthermore, groups of additional mice were included that were pre-exposed to low-dose photons before irradiating with acute photons, protons, and simulated solar particle event (SPE) protons. Hence, the original support together with the additional funding for our research led to generation of much valuable information that was originally not anticipated. Some of the data has already resulted in published articles, manuscripts in review, and a number of presentations at scientific conferences and workshops. Difficulties in reliable and reproducible quantification of secreted cytokines using multi-plex technology delayed completion of this study for a period of time. However, final analyses of the remaining data are currently being performed and should result in additional publications and presentations in the near future. Some of the most notable conclusions, thus far, are briefly summarized below: - Distribution of leukocytes were dependent upon cell type, radiation quality, body compartment analyzed, and time after exposure. Low-dose protons tended to have less effect on numbers of major leukocyte populations and T cell subsets compared to low-dose photons. - The patterns of gene and cytokine expression in CD4+ T cells after protracted low-dose irradiation were significantly modified and highly dependent upon the total dose and time after exposure. - Patterns of gene and cytokine expression differed substantially among groups exposed to low-dose photons versus low-dose protons; differences were also noted among groups exposed to much higher doses of photons, protons, and simulated SPE protons. - Some measurements indicated that exposure to low-dose photon radiation, especially 0.01 Gy, significantly “normalized” at least some adverse effects of simulated SPE protons, thereby suggesting that this low level of radiation may induce protective mechanisms against a relatively large radiation event. - Analysis of signal transduction pathways in CD4+ T cells showed that whole-body priming with 0.01 Gy photons before exposure to simulated SPE protons significantly increased expression of p38MAPK and NF-kappaB, while JNK expression was decreased. Overall, it appears that the p38MAPK signaling pathway may be most important in inducing a radioprotective response.« less

Effect of follow-up period on minimal-significant dose in the atomic-bomb survivor studies.

PubMed

Cologne, John; Preston, Dale L; Grant, Eric J; Cullings, Harry M; Ozasa, Kotaro

2018-03-01

It was recently suggested that earlier reports on solid-cancer mortality and incidence in the Life Span Study of atomic-bomb survivors contain still-useful information about low-dose risk that should not be ignored, because longer follow-up may lead to attenuated estimates of low-dose risk due to longer time since exposure. Here it is demonstrated, through the use of all follow-up data and risk models stratified on period of follow-up (as opposed to sub-setting the data by follow-up period), that the appearance of risk attenuation over time may be the result of less-precise risk estimation-in particular, imprecise estimation of effect-modification parameters-in the earlier periods. Longer follow-up, in addition to allowing more-precise estimation of risk due to larger numbers of radiation-related cases, provides more-precise adjustment for background mortality or incidence and more-accurate assessment of risk modification by age at exposure and attained age. It is concluded that the latest follow-up data are most appropriate for inferring low-dose risk. Furthermore, if researchers are interested in effects of time since exposure, the most-recent follow-up data should be considered rather than the results of earlier reports.

Effects of carbaryl on green frog (Rana clamitans) tadpoles: Timing of exposure versus multiple exposures

USGS Publications Warehouse

Boone, M.D.; Bridges, C.M.

2003-01-01

The majority of studies on pesticide impacts have evaluated the effects of single exposures. However, multiple exposures to a pesticide may be more prevalent. The objective of our study was to determine how multiple exposures versus single exposure at different times during development affected survival to metamorphosis, tadpole survival, tadpole mass, and tadpole developmental stage of green frog (Rana clamitans) tadpoles reared at low and high density in outdoor cattle tank ponds. Tadpoles were exposed to carbaryl zero, one, two, or three times at 14-d intervals. We applied single doses of carbaryl at one of three times, specifically during early, mid, or late development. Overall, we found that multiple exposures had a greater impact than single exposures during development. More individuals reached metamorphosis in ponds exposed to multiple doses of carbaryl compared with controls, indicating that the presence of carbaryl stimulated metamorphosis. The presence of carbaryl in the aquatic environment also resulted in more developed tadpoles compared with controls. Tadpoles in control ponds did not reach metamorphosis and were less developed than individuals exposed to carbaryl; this effect indicates that, under ideal conditions, green frogs could overwinter in ponds so that greater size could be attained before metamorphosis in the following spring or summer. Our study demonstrated the importance of including realistic application procedures when evaluating the effects of a pesticide and that multiple exposures to a short-lived pesticide are more likely to affect an amphibian population.

TU-D-209-05: Automatic Calculation of Organ and Effective Dose for CBCT and Interventional Fluoroscopic Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiong, Z; Vijayan, S; Oines, A

Purpose: To compare PCXMC and EGSnrc calculated organ and effective radiation doses from cone-beam computed tomography (CBCT) and interventional fluoroscopically-guided procedures using automatic exposure-event grouping. Methods: For CBCT, we used PCXMC20Rotation.exe to automatically calculate the doses and compared the results to those calculated using EGSnrc with the Zubal patient phantom. For interventional procedures, we use the dose tracking system (DTS) which we previously developed to produce a log file of all geometry and exposure parameters for every x-ray pulse during a procedure, and the data in the log file is input into PCXMC and EGSnrc for dose calculation. A MATLABmore » program reads data from the log files and groups similar exposures to reduce calculation time. The definition files are then automatically generated in the format used by PCXMC and EGSnrc. Processing is done at the end of the procedure after all exposures are completed. Results: For the Toshiba Infinix CBCT LCI-Middle-Abdominal protocol, most organ doses calculated with PCXMC20Rotation closely matched those calculated with EGSnrc. The effective doses were 33.77 mSv with PCXMC20Rotation and 32.46 mSv with EGSnrc. For a simulated interventional cardiac procedure, similar close agreement in organ dose was obtained between the two codes; the effective doses were 12.02 mSv with PCXMC and 11.35 mSv with EGSnrc. The calculations can be completed on a PC without manual intervention in less than 15 minutes with PCXMC and in about 10 hours with EGSnrc, depending on the level of data grouping and accuracy desired. Conclusion: Effective dose and most organ doses in CBCT and interventional radiology calculated by PCXMC closely match those calculated by EGSnrc. Data grouping, which can be done automatically, makes the calculation time with PCXMC on a standard PC acceptable. This capability expands the dose information that can be provided by the DTS. Partial support from NIH Grant R01-EB002873 and Toshiba Medical Systems Corp.« less

Age-Based Methods to Explore Time-Related Variables in Occupational Epidemiology Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Janice P. Watkins, Edward L. Frome, Donna L. Cragle

2005-08-31

Although age is recognized as the strongest predictor of mortality in chronic disease epidemiology, a calendar-based approach is often employed when evaluating time-related variables. An age-based analysis file, created by determining the value of each time-dependent variable for each age that a cohort member is followed, provides a clear definition of age at exposure and allows development of diverse analytic models. To demonstrate methods, the relationship between cancer mortality and external radiation was analyzed with Poisson regression for 14,095 Oak Ridge National Laboratory workers. Based on previous analysis of this cohort, a model with ten-year lagged cumulative radiation doses partitionedmore » by receipt before (dose-young) or after (dose-old) age 45 was examined. Dose-response estimates were similar to calendar-year-based results with elevated risk for dose-old, but not when film badge readings were weekly before 1957. Complementary results showed increasing risk with older hire ages and earlier birth cohorts, since workers hired after age 45 were born before 1915, and dose-young and dose-old were distributed differently by birth cohorts. Risks were generally higher for smokingrelated than non-smoking-related cancers. It was difficult to single out specific variables associated with elevated cancer mortality because of: (1) birth cohort differences in hire age and mortality experience completeness, and (2) time-period differences in working conditions, dose potential, and exposure assessment. This research demonstrated the utility and versatility of the age-based approach.« less

Persistent activation of nuclear factor-kappa B and expression of pro-inflammatory cytokines in bone marrow cells after exposure of mice to protons

NASA Astrophysics Data System (ADS)

Rithidech, Kanokporn; Reungpatthanaphong, Paiboon; Honikel, Louise; Whorton, Elbert

Protons are the most abundant component of solar particle events (SPEs) in space. Information is limited on early-and late-occurring in vivo biological effects of exposure to protons at doses and dose rates that are similar to what astronauts encounter in space. We conducted a study series to fill this knowledge gap. We focused on the biological effects of 100 MeV/n protons, which are one of the most abundant types of protons induced during SPEs. We gave BALB/cJ mice a whole-body exposure to 0.5 or 1.0 Gy of 100 MeV/n protons, delivered at 0.5 or 1.0 cGy/min. These doses and dose rates of protons were selected because they are comparable to those of SPEs taking place in space. For each dose and dose rate of 100 MeV/n protons, mice exposed to 0 Gy of protons served as sham controls. Mice included in this study were also part of a study series conducted to examine the extent and the mechanisms involved in in vivo induction of genomic instability (expressed as late-occurring chromosome instability) by 100 MeV/n protons. Bone marrow (BM) cells were collected from groups of mice for analyses at different times post-exposure, i.e. early time-points (1.5, 3, and 24 hr) and late time-points (1 and 6 months). At each harvest time, there were five mice per treatment group. Several endpoints were used to investigate the biological effects of 100 MeV/n protons in BM cells from irradiated and sham control mice. The scope of this study was to determine the dose-rate effects of 0.5 Gy of 100 MeV/n protons in BM cells on the kinetics of nuclear factor-kappa B (NF-kappa B) activation and the expression of selected NF-kappa B target proteins known to be involved in inflammatory response, i.e. pro-inflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6). Significantly high levels (p values ranging from p¡0.01 and p¡0.05) of activated NF-kappa B were observed in BM cells collected from irradiated mice, relative to those obtained from the corresponding sham controls, at all time-points included in the study, regardless of the dose rate of proton-irradiation. However, these increases were more pronounced when the higher dose rate (1.0 cGy/min) was used. The results indicated that NF-kappa B activation in BM cells persisted up to 6 months after exposure of mice to a single dose of 0.5 Gy of 100 MeV/n protons, delivered at the dose rates occurring in space. Further, significantly up-regulated levels of TNF-alpha were detected in BM cells of exposed mice (p values ranging from p¡0.01 and p¡0.05), compared to those in the corresponding sham controls, at all harvest times, in spite of the difference in dose rate of proton-irradiation. However, steady increases in the levels of IL-1 beta and IL-6 in BM cells of exposed mice over the levels in their sham controls across all time-points included in the study were detected only when a dose rate of 1.0 cGy/min was used. In contrast, with a dose rate of 0.5 cGy/min, significantly high expression levels of these two pro-inflammatory cytokines were consistently found in BM cells collected from exposed mice at late time-points only. In summary, our data provide important information for space flight missions because the findings of persistent activation of NF-kappa B and expression of pro-inflammatory cytokines suggest the occurrence of chronic inflammation after exposure of mice to 100 MeV/n protons that, in turn, may have an important impact on health outcome during space flights. Knowledge gained on the NF-kappa B pathway from this study could, therefore, be useful for planning countermeasure strategies to protect astronauts or space travelers in the space environment. Research funded by NASA Grant NNX07AP88G.

Real-Time Patient and Staff Radiation Dose Monitoring in IR Practice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sailer, Anna M., E-mail: karmanna@stanford.edu; Paulis, Leonie, E-mail: leonie.paulis@mumc.nl; Vergoossen, Laura

PurposeKnowledge of medical radiation exposure permits application of radiation protection principles. In our center, the first dedicated real-time, automated patient and staff dose monitoring system (DoseWise Portal, Philips Healthcare) was installed. Aim of this study was to obtain insight in the procedural and occupational doses.Materials and MethodsAll interventional radiologists, vascular surgeons, and technicians wore personal dose meters (PDMs, DoseAware, Philips Healthcare). The dose monitoring system simultaneously registered for each procedure dose-related data as the dose area product (DAP) and effective staff dose (E) from PDMs. Use and type of shielding were recorded separately. All procedures were analyzed according to proceduremore » type; these included among others cerebral interventions (n = 112), iliac and/or caval venous recanalization procedures (n = 68), endovascular aortic repair procedures (n = 63), biliary duct interventions (n = 58), and percutaneous gastrostomy procedure (n = 28).ResultsMedian (±IQR) DAP doses ranged from 2.0 (0.8–3.1) (percutaneous gastrostomy) to 84 (53–147) Gy cm{sup 2} (aortic repair procedures). Median (±IQR) first operator doses ranged from 1.6 (1.1–5.0) μSv to 33.4 (12.1–125.0) for these procedures, respectively. The relative exposure, determined as first operator dose normalized to procedural DAP, ranged from 1.9 in biliary interventions to 0.1 μSv/Gy cm{sup 2} in cerebral interventions, indicating large variation in staff dose per unit DAP among the procedure types.ConclusionReal-time dose monitoring was able to identify the types of interventions with either an absolute or relatively high staff dose, and may allow for specific optimization of radiation protection.« less

Ultrasound assisted chrome tanning: Towards a clean leather production technology.

PubMed

Mengistie, Embialle; Smets, Ilse; Van Gerven, Tom

2016-09-01

Nowadays, there is a growing demand for a cleaner, but still effective alternative for production processes like in the leather industry. Ultrasound (US) assisted processing of leather might be promising in this sense. In the present paper, the use of US in the conventional chrome tanning process has been studied at different pH, temperature, tanning time, chrome dose and US exposure time by exposing the skin before tanning and during tanning operation. Both prior exposure of the skin to US and US during tanning improves the chrome uptake and reduces the shrinkage significantly. Prior exposure of the skin to US increase the chrome uptake by 13.8% or reduces the chrome dose from 8% to 5% (% based on skin weight) and shorten the process time by half while US during tanning increases the chrome uptake by 28.5% or reduces the chrome dose from 8% to 4% (half) and the tanning time to one third compared to the control without US. Concomitantly, the resulting leather quality (measured as skin shrinkage) improved from 5.2% to 3.2% shrinkage in the skin exposed to US prior tanning and to 1.3% in the skin exposed to US during the tanning experiment. This study confirms that US chrome tanning is an effective and eco-friendly tanning process which can produce a better quality leather product in a shorter process time with a lower chromium dose. Copyright © 2016 Elsevier B.V. All rights reserved.

Dose- and time-dependent pharmacokinetics of apigenin trimethyl ether.

PubMed

Elhennawy, Mai Gamal; Lin, Hai-Shu

2018-06-15

Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE), one of the key polymethoxyflavones present in black ginger (rhizome of Kaempferia parviflora) possesses various health-promoting activities. To optimize its medicinal application, the pharmacokinetics of ATE was assessed in Sprague-Dawley rats with emphases to identify the impacts from dose and repeated dosing on its major pharmacokinetic parameters. Plasma ATE levels were monitored by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Upon single intravenous administration (2 mg/kg), plasma levels of ATE declined through an apparent first-order process while dose-escalation to 4 and 8 mg/kg led to its non-linear disposition, which could be described by the Michaelis-Menten model. Similarly, dose-dependent oral pharmacokinetics was confirmed and when the dose was escalated from 5 to 15 and 45 mg/kg, much longer mean residence time (MRT 0→last ), higher dose-normalized maximal plasma concentration (C max /Dose) and exposure (AUC/Dose) were observed at 15 and/or 45 mg/kg. One-week daily oral administration of ATE at 15 mg/kg caused its accelerated elimination and the plasma exposure (AUC) after intravenous (2 mg/kg) and oral administration (15 mg/kg) dropped ~40 and 60%, respectively. As ATE displayed both dose- and time-dependent pharmacokinetics, caution is needed in the medicinal applications of ATE and/or black ginger. Copyright © 2018 Elsevier B.V. All rights reserved.

Laser-based irradiation apparatus and methods for monitoring the dose-rate response of semiconductor devices

DOEpatents

Horn, Kevin M [Albuquerque, NM

2006-03-28

A scanned, pulsed, focused laser irradiation apparatus can measure and image the photocurrent collection resulting from a dose-rate equivalent exposure to infrared laser light across an entire silicon die. Comparisons of dose-rate response images or time-delay images from before, during, and after accelerated aging of a device, or from periodic sampling of devices from fielded operational systems allows precise identification of those specific age-affected circuit structures within a device that merit further quantitative analysis with targeted materials or electrical testing techniques. Another embodiment of the invention comprises a broad-beam, dose rate-equivalent exposure apparatus. The broad-beam laser irradiation apparatus can determine if aging has affected the device's overall functionality. This embodiment can be combined with the synchronized introduction of external electrical transients into a device under test to simulate the electrical effects of the surrounding circuitry's response to a radiation exposure.

Dose-response relationship between light exposure and cycling performance.

PubMed

Knaier, R; Meister, S; Aeschbacher, T; Gemperle, D; Rossmeissl, A; Cajochen, C; Schmidt-Trucksäss, A

2016-07-01

Light has a stimulating effect on physical performance if scheduled according to the chronotype, but dose-dependent effects on performance have not yet been examined. Three groups of healthy men (25.1 ± 3.1 years) were exposed to light for different durations in a parallel group design before a 40-min time-trial. In each group, subjects were exposed to either bright light (BL, 4420 lx) or moderate light (ML, 230 lx) in a randomized order in a crossover design. The durations of light exposure were 120 min prior to and during exercise (2HEX; n = 16), 60 min prior to and during exercise (1HEX; n = 10), or only for 60 min prior to exercise (1H; n = 15). Total work performed during the time-trial in kJ in the 2HEX group was significantly higher in the BL setting (527 kJ) than in ML (512 kJ) (P = 0.002), but not in 1HEX (BL: 485 kJ; ML: 498 kJ) or 1H (BL: 519 kJ; ML: 514 kJ) (P = 0.770; P = 0.485). There was a significant (P = 0.006) positive dose-response relationship between the duration of light exposure and the work performed over the three doses of light exposure. A long duration light exposure is an effective tool to increase total work in a medium length time-trial in subjects normalized for their individual chronotype. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Radiological Risk Assessment of Capstone Depleted Uranium Aerosols

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hahn, Fletcher; Roszell, Laurie E.; Daxon, Eric G.

2009-02-26

Assessment of the health risk from exposure to aerosols of depleted uranium (DU) is an important outcome of the Capstone aerosol studies that established exposure ranges to personnel in armored combat vehicles perforated by DU munitions. Although the radiation exposure from DU is low, there is concern that DU deposited in the body may increase cancer rates. Radiation doses to various organs of the body resulting from the inhalation of DU aerosols measured in the Capstone studies were calculated using International Commission on Radiological Protection (ICRP) models. Organs and tissues with the highest calculated committed equivalent 50-yr doses were lungmore » and extrathoracic tissues (nose and nasal passages, pharynx, larynx, mouth and thoracic lymph nodes). Doses to the bone surface and kidney were about 5 to 10% of the doses to the extrathoracic tissues. The methodologies of the ICRP International Steering Committee on Radiation Standards (ISCORS) were used for determining the whole body cancer risk. Organ-specific risks were estimated using ICRP and U.S. Environmental Protection Agency (EPA) methodologies. Risks for crewmembers and first responders were determined for selected scenarios based on the time interval of exposure and for vehicle and armor type. The lung was the organ with the highest cancer mortality risk, accounting for about 97% of the risks summed from all organs. The highest mean lifetime risk for lung cancer for the scenario with the longest exposure time interval (2 h) was 0.42%. This risk is low compared with the natural or background risk of 7.35%. These risks can be significantly reduced by using an existing ventilation system (if operable) and by reducing personnel time in the vehicle immediately after perforation.« less

[Dose and image quality in intraoral radiography].

PubMed

Hjardemaal, O

1991-11-01

The technique factors when performing intraoral X-ray exposures must be selected in such a way that sufficient diagnostic information is obtained at a reasonable patient dose. The Danish National Institute of Radiation Hygiene has performed a study comprising 32 dental X-ray sets. The mean value of the skin dose for a maxillary molar was 9.6 mGy and the value for the dental colleges 7.0 mGy. For a mandibular incisor the corresponding doses were 7.7 mGy and 3.6 mGy. After the conclusion of the mentioned study it has been part of the institute's inspection procedure for dental X-ray sets to measure patient skin doses. 243 measurements were performed and the mean value of the entrance skin dose was 6.5 mGy and the dose interval was 0.7-57 mGy. All doses are normalised to speed class D film. At 16% of the inspected sets films of speed class E were used. The remainder used class D films. The spread in doses cannot be explained by variation in equipment parameters alone but is to a high degree due to a combination of inappropriate film processing and exposure time. Interviews with staff in dental clinics confirm that films are frequently processed until the desired density is obtained by visual estimation. It is shown that the skin dose when using film of speed class D can be kept below 7 mGy for a mandibular incisor. Concluding is stated that film processing shall be performed in accordance with specifications from the manufacturer of the developer. Film of speed class E must be used. Finally must the exposure time be graduated according to the object exposed.

Achieving a physiological cortisol profile with once-daily dual-release hydrocortisone: a pharmacokinetic study.

PubMed

Johannsson, Gudmundur; Lennernäs, Hans; Marelli, Claudio; Rockich, Kevin; Skrtic, Stanko

2016-07-01

Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy was developed to provide a cortisol exposure-time profile that closely resembles the physiological cortisol profile. This study aimed to characterize single-dose pharmacokinetics (PK) of DR-HC 5-20mg and assess intrasubject variability. Thirty-one healthy Japanese or non-Hispanic Caucasian volunteers aged 20-55 years participated in this randomized, open-label, PK study. Single doses of DR-HC 5, 15 (3×5), and 20mg were administered orally after an overnight fast and suppression of endogenous cortisol secretion. After estimating the endogenous cortisol profile, PK of DR-HC over 24h were evaluated to assess dose proportionality and impact of ethnicity. Plasma cortisol concentrations were analyzed using liquid chromatography-tandem mass spectrometry. PK parameters were calculated from individual cortisol concentration-time profiles. DR-HC 20mg provided higher than endogenous cortisol plasma concentrations 0-4h post-dose but similar concentrations later in the profile. Cortisol concentrations and PK exposure parameters increased with increasing doses. Mean maximal serum concentration (Cmax) was 82.0 and 178.1ng/mL, while mean area under the concentration-time curve (AUC)0-∞ was 562.8 and 1180.8h×ng/mL with DR-HC 5 and 20mg respectively. Within-subject PK variability was low (<15%) for DR-HC 20mg. All exposure PK parameters were less than dose proportional (slope <1). PK differences between ethnicities were explained by body weight differences. DR-HC replacement resembles the daily normal cortisol profile. Within-subject day-to-day PK variability was low, underpinning the safety of DR-HC for replacement therapy. DR-HC PK were less than dose proportional - an important consideration when managing intercurrent illness in patients with adrenal insufficiency. © 2016 The authors.

Analysis of Radiation Exposure for Troop Observers, Exercise Desert Rock V, Operation Upshot-Knothole.

DTIC Science & Technology

1981-04-28

on initial doses. Residual doses are determined through an automiated procedure that utilizes raw data in regression analyses to fit space-time models...show their relationship to the observer positions. The computer-calculated doses do not reflect the presence of the human body in the radiological

Molecular and Histopathological Changes in Mouse Intestinal Tissue after Proton Exposure

NASA Astrophysics Data System (ADS)

Purgason, Ashley; Zhang, Ye; Hamilton, Stanley; Wu, Honglu

Radiation in space, especially energetic protons emitted from solar particle events (SPEs), poses serious health risks to astronauts and is especially dangerous for long duration missions. Protons are the most abundant particles in space and to date there is little known about the details of the negative consequences crew members will face upon exposure to them. To elucidate some of the possible health effects induced by protons, BALB/C mice were subjected to 250 MeV of proton radiation at doses of 0 Gy, 0.1 Gy, 1 Gy, and 2 Gy. Three specimens per dose were studied. The gastrointestinal tract of each animal was dissected four hours post-irradiation and the isolated small intestinal tissue was fixed in formalin for histopathological examination or snap-frozen in liquid nitrogen for RNA isolation. Histopathologic observation of the tissue using standard HE staining methods to screen for morphologic changes showed a marked increase in apoptotic lesions for even the lowest dose of 0.1 Gy, and the dose response showed possible hyper sensitivities at low dose. Tissue of the gastrointestinal tract was also homogenized and RNA was isolated for cDNA synthesis and real-time PCR analysis for genes involved in apoptosis. Results of gene expression changes revealed consistent up or down regulation of a number of genes for all of the exposure doses that may play a role in proton-induced apoptosis (e.g. Hsp90ab1). In addition, several genes were found to have significant changes in the RNA level after only the low dose (0.1 Gy), but not the high dose (1 and 2 Gy), proton exposures (e.g. Bok and Casp1), whereas some genes had expression changes only after high dose proton exposures (e.g. Tsc22d3). These findings demonstrated that apoptosis may occur in gastrointestinal tracts after even low dose proton exposures, and the different gene expression patterns between low and high dose proton irradiated mice may offer insight into the molecular mechanisms of the possible hyper sensitivity at low proton doses.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McChesney, D.G.; Ledney, G.D.; Madonna, G.S.

The survival of B6D2F1 female mice exposed to lethal doses of fission neutron radiation is increased when trehalose dimycolate (TDM) preparations are given either 1 h after exposure or 1 day before exposure to radiation. TDM in an emulsion of squalene, Tween 80, and saline was the most effective formulation for increasing the 30-day survival of mice when given 1 day before (90%) or 1 h after (88%) exposure to radiation. An aqueous suspension of a synthetic analog of TDM was less effective at increasing 30-day survival (60%) when given 1 day prior to radiation exposure and not effective whenmore » given 1 h after radiation. Mice receiving a sublethal dose (3.5 Gy) of fission neutron radiation and either the TDM emulsion or synthetic TDM 1 h after irradiation were substantially more resistant to challenge with 10, 100, 1000, or 5000 times the LD50/30 dose of Klebsiella pneumoniae than untreated mice.« less

Investigation on circular asymmetry of geographical distribution in cancer mortality of Hiroshima atomic bomb survivors based on risk maps: analysis of spatial survival data.

PubMed

Tonda, Tetsuji; Satoh, Kenichi; Otani, Keiko; Sato, Yuya; Maruyama, Hirofumi; Kawakami, Hideshi; Tashiro, Satoshi; Hoshi, Masaharu; Ohtaki, Megu

2012-05-01

While there is a considerable number of studies on the relationship between the risk of disease or death and direct exposure from the atomic bomb in Hiroshima, the risk for indirect exposure caused by residual radioactivity has not yet been fully evaluated. One of the reasons is that risk assessments have utilized estimated radiation doses, but that it is difficult to estimate indirect exposure. To evaluate risks for other causes, including indirect radiation exposure, as well as direct exposure, a statistical method is described here that evaluates risk with respect to individual location at the time of atomic bomb exposure instead of radiation dose. In addition, it is also considered to split the risks into separate risks due to direct exposure and other causes using radiation dose. The proposed method is applied to a cohort study of Hiroshima atomic bomb survivors. The resultant contour map suggests that the region west to the hypocenter has a higher risk compared to other areas. This in turn suggests that there exists an impact on risk that cannot be explained by direct exposure.

Gestational Alcohol Exposure Altered DNA Methylation Status in the Developing Fetus

PubMed Central

Mandal, Chanchal; Halder, Debasish; Jung, Kyoung Hwa; Chai, Young Gyu

2017-01-01

Ethanol is well known as a teratogenic factor that is capable of inducing a wide range of developmental abnormalities if the developing fetus is exposed to it. Duration and dose are the critical parameters of exposure that affect teratogenic variation to the developing fetus. It is suggested that ethanol interferes with epigenetic processes especially DNA methylation. We aimed to organize all of the available information on the alteration of DNA methylation by ethanol in utero. Thus, we have summarized all published information regarding alcohol-mediated alterations in DNA methylation during gestation. We tried to arrange information in a way that anyone can easily find the alcohol exposure time, doses, sampling time, and major changes in genomic level. Manuscript texts will also represent the correlation between ethanol metabolites and subsequent changes in methylome patterns. We hope that this review will help future researchers to further examine the issues associated with ethanol exposure. PMID:28657590

Immediate effects of 33 to 180 rad/min (60)Co exposure on performance and blood pressure in monkeys. Topical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruner, A.

1976-09-01

Four groups of monkeys received 1000 rads (60)Co at 33, 50, 75, or 180 rad/min wholebody irradiation while performing a delayed matching-to-sample task. Systematic dose rate effects were observed on performance and blood pressure within the initial 20 min postirradiation. The incidence and severity of performance decrement (PD) increased with higher dose rate. The appearance of postirradiation hypotension was systematically delayed and its rate of fall prolonged as dose rate was lower. The hypotension likewise appeared less deep with lower dose rate exposure. Based on the calculated cumulative dose absorbed at the time of symptom appearance two coactive thresholds weremore » proposed to exist: a total dose threshold of approximately 300 rads (midbody measurement), and a dose rate threshold of about 25 rad/min.« less

Low-energy electron effects on tensile modulus and infrared transmission properties of a polypyromellitimide film

NASA Technical Reports Server (NTRS)

Ferl, J. E.; Long, E. R., Jr.

1981-01-01

Infrared (IR) spectroscopy and tensile modulus testing were used to evaluate the importance of experimental procedure on changes in properties of pyromellitic dianhydride-p,p prime-oxydianiline film exposed to electron radiation. The radiation exposures were accelerated, approximate equivalents to the total dose expected for a 30 year mission in geosynchronous Earth orbit. The change in the tensile modulus depends more on the dose rate and the time interval between exposure and testing than on total dose. The IR data vary with both total dose and dose rate. A threshold dose rate exists below which reversible radiation effects on the IR spectra occur. Above the threshold dose rate, irreversible effects occur with the appearance of a new band. Post-irradiation and in situ IR absorption bands are significantly different. It is suggested that the electron radiation induced metastable, excites molecular states.

Experimental ultraviolet photocarcinogenesis: wavelength interactions and time-dose relationships.

PubMed

Forbes, P D; Davies, R E; Urbach, F

1978-12-01

Tumors were induced in the skin of SKH hairless mice by exposure to fluorescent FS sun lamps or to a long-arc xenon solar simulator. Tumores developed about equally well with varying amounts of UV-A radiation (lambda greater than 320 nm) given simultaneously. In contrast, incremental changes in the UV-B region (lambda less than 320 nm) led to substantial increases in carcinogenic effectiveness. A tumor-"initiating" dose of UV-B (4-10 wk of daily FS lamp exposures) was rendered less effective by subsequent exposures of the mice to UV-A (6 hr/day, F-40 T12BL lamps). The mechanism for this effect is not known. Most tumors induced by a short course (10 wk) of FS lamp exposure grew slowly or regressed, whereas mice exposed for a longer period (30 wk) developed more tumors, and many of those that appeared early grew aggressively. Effects of daily dose fractionation were less clear, and the subject requires further study. These and other variables are being tested in a program designed to yield useful information on the effects of changing spectrum, dose, and dose delivery rates on sunlight-induced cancer.

Human exposure to large solar particle events in space

NASA Technical Reports Server (NTRS)

Townsend, L. W.; Wilson, J. W.; Shinn, J. L.; Curtis, S. B.

1992-01-01

Whenever energetic solar protons produced by solar particle events traverse bulk matter, they undergo various nuclear and atomic collision processes which significantly alter the physical characteristics and biologically important properties of their transported radiation fields. These physical interactions and their effect on the resulting radiation field within matter are described within the context of a recently developed deterministic, coupled neutron-proton space radiation transport computer code (BRYNTRN). Using this computer code, estimates of human exposure in interplanetary space, behind nominal (2 g/sq cm) and storm shelter (20 g/sq cm) thicknesses of aluminum shielding, are made for the large solar proton event of August 1972. Included in these calculations are estimates of cumulative exposures to the skin, ocular lens, and bone marrow as a function of time during the event. Risk assessment in terms of absorbed dose and dose equivalent is discussed for these organs. Also presented are estimates of organ exposures for hypothetical, worst-case flare scenarios. The rate of dose equivalent accumulation places this situation in an interesting region of dose rate between the very low values of usual concern in terrestrial radiation environments and the high-dose-rate values prevalent in radiation therapy.

Heavy construction equipment noise study using dosimetry and time-motion studies

NASA Astrophysics Data System (ADS)

Spencer, Ellsworth R.; Yantek, David S.

2005-09-01

Noise-induced hearing loss continues to afflict workers in many occupational settings despite longstanding recognition of the problems and well-known methods of prevention and regulations. Sound levels associated with heavy construction equipment range from 80 to 120 dB(A) and power tools commonly used in construction produce sound levels up to 115 dB(A). The focus of the research was to determine the noise exposures of heavy construction equipment operators while documenting the workers' tasks, (i.e., hauling, moving, and/or pushing construction material). Time-motion studies were performed at the construction sites and were used to correlate the noise dosage with the work performed by equipment operators. The cumulative dose for the operator was then plotted with references to work tasks, to identify the tasks that caused the greatest noise exposure. Three construction sites were examined and located in the western Pennsylvania and eastern Ohio areas. The types of construction equipment studied included asphalt pavers, backhoes, bulldozers, compaction equipment, excavators, haul trucks, telehandlers, and wheeled loaders. The results showed that bulldozer operators consistently had the highest noise exposures, ranging from a NIOSH REL (Recommended Exposure Limit) dose of 844% to 25836% and an OSHA PEL (Permissible Exposure Limit) dose of 139% to 1397%.

Doses of Nearby Nature Simultaneously Associated with Multiple Health Benefits

PubMed Central

Cox, Daniel T. C.; Shanahan, Danielle F.; Hudson, Hannah L.; Fuller, Richard A.; Anderson, Karen; Hancock, Steven; Gaston, Kevin J.

2017-01-01

Exposure to nature provides a wide range of health benefits. A significant proportion of these are delivered close to home, because this offers an immediate and easily accessible opportunity for people to experience nature. However, there is limited information to guide recommendations on its management and appropriate use. We apply a nature dose-response framework to quantify the simultaneous association between exposure to nearby nature and multiple health benefits. We surveyed ca. 1000 respondents in Southern England, UK, to determine relationships between (a) nature dose type, that is the frequency and duration (time spent in private green space) and intensity (quantity of neighbourhood vegetation cover) of nature exposure and (b) health outcomes, including mental, physical and social health, physical behaviour and nature orientation. We then modelled dose-response relationships between dose type and self-reported depression. We demonstrate positive relationships between nature dose and mental and social health, increased physical activity and nature orientation. Dose-response analysis showed that lower levels of depression were associated with minimum thresholds of weekly nature dose. Nearby nature is associated with quantifiable health benefits, with potential for lowering the human and financial costs of ill health. Dose-response analysis has the potential to guide minimum and optimum recommendations on the management and use of nearby nature for preventative healthcare. PMID:28208789

Doses of Nearby Nature Simultaneously Associated with Multiple Health Benefits.

PubMed

Cox, Daniel T C; Shanahan, Danielle F; Hudson, Hannah L; Fuller, Richard A; Anderson, Karen; Hancock, Steven; Gaston, Kevin J

2017-02-09

Exposure to nature provides a wide range of health benefits. A significant proportion of these are delivered close to home, because this offers an immediate and easily accessible opportunity for people to experience nature. However, there is limited information to guide recommendations on its management and appropriate use. We apply a nature dose-response framework to quantify the simultaneous association between exposure to nearby nature and multiple health benefits. We surveyed ca. 1000 respondents in Southern England, UK, to determine relationships between (a) nature dose type, that is the frequency and duration (time spent in private green space) and intensity (quantity of neighbourhood vegetation cover) of nature exposure and (b) health outcomes, including mental, physical and social health, physical behaviour and nature orientation. We then modelled dose-response relationships between dose type and self-reported depression. We demonstrate positive relationships between nature dose and mental and social health, increased physical activity and nature orientation. Dose-response analysis showed that lower levels of depression were associated with minimum thresholds of weekly nature dose. Nearby nature is associated with quantifiable health benefits, with potential for lowering the human and financial costs of ill health. Dose-response analysis has the potential to guide minimum and optimum recommendations on the management and use of nearby nature for preventative healthcare.

Etirinotecan pegol administration is associated with lower incidences of neutropenia compared to irinotecan administration.

PubMed

Sy, S Kenneth; Sweeney, Theresa D; Ji, Chunmei; Hoch, Ute; Eldon, Michael A

2017-01-01

The relationship between incidences of neutropenia and 10-hydroxy-7-ethyl camptothecin (SN38) exposure was explored using SN38 pharmacokinetic and neutrophil count data from toxicology studies of etirinotecan pegol (EP) and irinotecan in beagle dogs. Dogs received four weekly intravenous infusions of either vehicle control (n = 22), EP (6, 15, 20, 25, 40/25 mg/kg; n = 3-9 dogs/dose group/sex; n = 48), or irinotecan (20 or 25 mg/kg n = 3-4 dogs/dose group/sex; n = 14). Blood samples were collected up to 50 days post-dose for characterization of SN38 pharmacokinetics. Two separate models were created describing SN38 concentration time profiles after either irinotecan or EP administrations to project the AUC 0-168h after Day 1 and Day 22 doses. The relationship between incidence of neutropenia and SN38 exposure was explored using logistic regression. The incidence of neutropenia in dogs receiving weekly doses of irinotecan or EP was strongly correlated with maximum plasma SN38 concentration (C max ), but not SN38 area under the concentration-time curve (AUC). Neutropenia occurred in approximately 80% of dogs receiving irinotecan (mean SN38 C max of 13.5 and 26.3 ng/mL for 20 and 25 mg/kg, respectively). No neutropenia occurred in dogs receiving EP at doses up to and including 25 mg/kg (mean SN38 C max of 3.4 and 4.9 ng/mL for 20 and 25 mg/kg, respectively), despite 2.5-3.6 times greater SN38 AUC after EP compared to irinotecan at equivalent doses. EP administration avoids both high SN38 C max values and development of dose-limiting neutropenia observed after irinotecan, while maintaining greater and sustained SN38 exposure between doses.

Biology Based Lung Cancer Model for Chronic Low Radon Exposures

NASA Astrophysics Data System (ADS)

TruÅ£ǎ-Popa, Lucia-Adina; Hofmann, Werner; Fakir, Hatim; Cosma, Constantin

2008-08-01

Low dose effects of alpha particles at the tissue level are characterized by the interaction of single alpha particles, affecting only a small fraction of the cells within that tissue. Alpha particle intersections of bronchial target cells during a given exposure period were simulated by an initiation-promotion model, formulated in terms of cellular hits within the cycle time of the cell (dose-rate) and then integrated over the whole exposure period (dose). For a given average number of cellular hits during the lifetime of bronchial cells, the actual number of single and multiple hits was selected from a Poisson distribution. While oncogenic transformation is interpreted as the primary initiation step, stimulated mitosis by killing adjacent cells is assumed to be the primary radiological promotion event. Analytical initiation and promotion functions were derived from experimental in vitro data on oncogenic transformation and cellular survival. To investigate the shape of the lung cancer risk function at chronic, low level exposures in more detail, additional biological factors describing the tissue response and operating specifically at low doses were incorporated into the initiation-promotion model. These mechanisms modifying the initial response at the cellular level were: adaptive response, genomic instability, induction of apoptosis by surrounding cells, and detrimental as well as protective bystander mechanisms. To quantify the effects of these mechanisms as functions of dose, analytical functions were derived from the experimental evidence presently available. Predictions of lung cancer risk, including these mechanisms, exhibit a distinct sublinear dose-response relationship at low exposures, particularly for very low exposure rates.

Prototype Operational Advances for Atmospheric Radiation Dose Rate Specification

NASA Astrophysics Data System (ADS)

Tobiska, W. K.; Bouwer, D.; Bailey, J. J.; Didkovsky, L. V.; Judge, K.; Garrett, H. B.; Atwell, W.; Gersey, B.; Wilkins, R.; Rice, D.; Schunk, R. W.; Bell, D.; Mertens, C. J.; Xu, X.; Crowley, G.; Reynolds, A.; Azeem, I.; Wiltberger, M. J.; Wiley, S.; Bacon, S.; Teets, E.; Sim, A.; Dominik, L.

2014-12-01

Space weather's effects upon the near-Earth environment are due to dynamic changes in the energy transfer processes from the Sun's photons, particles, and fields. The coupling between the solar and galactic high-energy particles, the magnetosphere, and atmospheric regions can significantly affect humans and our technology as a result of radiation exposure. Space Environment Technologies (SET) has developed innovative, new space weather observations that will become part of the toolset that is transitioned into operational use. One prototype operational system for providing timely information about the effects of space weather is SET's Automated Radiation Measurements for Aerospace Safety (ARMAS) system. ARMAS will provide the "weather" of the radiation environment to improve aircraft crew and passenger safety. Through several dozen flights the ARMAS project has successfully demonstrated the operation of a micro dosimeter on commercial aviation altitude aircraft that captures the real-time radiation environment resulting from Galactic Cosmic Rays and Solar Energetic Particles. The real-time radiation exposure is computed as an effective dose rate (body-averaged over the radiative-sensitive organs and tissues in units of microsieverts per hour); total ionizing dose is captured on the aircraft, downlinked in real-time via Iridium satellites, processed on the ground into effective dose rates, compared with NASA's Langley Research Center (LaRC) most recent Nowcast of Atmospheric Ionizing Radiation System (NAIRAS) global radiation climatology model runs, and then made available to end users via the web and smart phone apps. We are extending the dose measurement domain above commercial aviation altitudes into the stratosphere with a collaborative project organized by NASA's Armstrong Flight Research Center (AFRC) called Upper-atmospheric Space and Earth Weather eXperiment (USEWX). In USEWX we will be flying on the ER-2 high altitude aircraft a micro dosimeter for effective dose rate measurements and a thermal neutron monitor to characterize Single Event Effects (SEEs) in avionics. In this presentation we describe recent ARMAS and USEWX advances that will ultimately provide operational users with real-time dose and dose rate data for human tissue and avionics exposure risk mitigation.

Radiation exposure of ventilated trauma patients in intensive care: a retrospective study comparing two time periods.

PubMed

Yee, Micaela V; Barron, Rochelle A; Knobloch, Tom A; Pandey, Umesh; Twyford, Catherine; Freebairn, Ross C

2012-08-01

To describe the cumulative effective dose of radiation that was received during the initial Emergency Department assessment and ICU stay of patients admitted with trauma, who required mechanical ventilation, during two time periods. A retrospective analysis of radiological and clinical data, set in a regional nonurban ICU. Two cohorts (starting 1 January 2004 and 1 January 2009), each comprising 45 adult patients admitted with trauma who were mechanically ventilated in intensive care, were studied. Frequency and type of radiological examinations, demographic information, and clinical data were collated from the radiological database, hospital admission record and Australian Outcomes Research Tool for Intensive Care database. Cumulative effective doses were calculated and expressed as a total dose and average daily dose for each cohort. The median cumulative effective dose per patient (in milliSieverts) increased from 34.59 [interquartile range (IQR) 9.08-43.91] in 2004 to 40.51 (IQR 22.01-48.87) in 2009, P=0.045. An increased number of computed tomography examinations per patient was also observed over the same interval from an average of 2.11 (median 2, IQR 1-3) in 2004 to an average of 2.62 (2, 2-4) in 2009, P=0.046. The radiation exposure of mechanically ventilated trauma patients in intensive care has increased over time. Radiation exposure should be prospectively monitored and staff should be aware of the increased risk resulting from this change in practice.

Persistence of Space Radiation Induced Cytogenetic Damage in the Blood Lymphocytes of Astronauts

NASA Technical Reports Server (NTRS)

George, Kerry; Cucinotta, Francis A.

2008-01-01

Cytogenetic damage in astronaut's peripheral blood lymphocytes is a useful in vivo marker of space radiation induced damage. Moreover, if radiation induced chromosome translocations persist in peripheral blood lymphocytes for many years, as has been assumed, they could potentially be used to measure retrospective doses or prolonged low dose rate exposures. However, as more data becomes available, evidence suggests that the yield of translocations may decline with time after exposure, at least in the case of space radiation exposures. We present our latest follow-up measurements of chromosome aberrations in astronauts blood lymphocytes assessed by FISH painting and collected a various times beginning directly after return from space to several years after flight. For most individuals the analysis of individual time-courses for translocations revealed a temporal decline of yields with different half-lives. Since the level of stable aberrations depends on the interplay between natural loss of circulating T-lymphocytes and replenishment from the stem or progenitor cells, the differences in the rates of decay could be explained by inter-individual variation in lymphocyte turn over. Biodosimetry estimates derived from cytogenetic analysis of samples collected a few days after return to earth lie within the range expected from physical dosimetry. However, a temporal decline in yields may indicate complications with the use of stable aberrations for retrospective dose reconstruction, and the differences in the decay time may reflect individual variability in risk from space radiation exposure. In addition, limited data on multiple flights show a lack of correlation between time in space and translocation yields. Data from one crewmember who has participated in two separate long-duration space missions and has been followed up for over 10 years provides limited information on the effect of repeat flights and show a possible adaptive response to space radiation exposure.

A real-time regional adaptive exposure method for saving dose-area product in x-ray fluoroscopy

PubMed Central

Burion, Steve; Speidel, Michael A.; Funk, Tobias

2013-01-01

Purpose: Reduction of radiation dose in x-ray imaging has been recognized as a high priority in the medical community. Here the authors show that a regional adaptive exposure method can reduce dose-area product (DAP) in x-ray fluoroscopy. The authors' method is particularly geared toward providing dose savings for the pediatric population. Methods: The scanning beam digital x-ray system uses a large-area x-ray source with 8000 focal spots in combination with a small photon-counting detector. An imaging frame is obtained by acquiring and reconstructing up to 8000 detector images, each viewing only a small portion of the patient. Regional adaptive exposure was implemented by varying the exposure of the detector images depending on the local opacity of the object. A family of phantoms ranging in size from infant to obese adult was imaged in anteroposterior view with and without adaptive exposure. The DAP delivered to each phantom was measured in each case, and noise performance was compared by generating noise arrays to represent regional noise in the images. These noise arrays were generated by dividing the image into regions of about 6 mm2, calculating the relative noise in each region, and placing the relative noise value of each region in a one-dimensional array (noise array) sorted from highest to lowest. Dose-area product savings were calculated as the difference between the ratio of DAP with adaptive exposure to DAP without adaptive exposure. The authors modified this value by a correction factor that matches the noise arrays where relative noise is the highest to report a final dose-area product savings. Results: The average dose-area product saving across the phantom family was (42 ± 8)% with the highest dose-area product saving in the child-sized phantom (50%) and the lowest in the phantom mimicking an obese adult (23%). Conclusions: Phantom measurements indicate that a regional adaptive exposure method can produce large DAP savings without compromising the noise performance in the image regions with highest noise. PMID:23635281

Effects of age on the disruption of cognitive performance by exposure to space radiation

USDA-ARS?s Scientific Manuscript database

Exposure to low doses of heavy particles and protons can cause deficits in cognitive performance when measured within a short time (1-4 months) following irradiation. The long-term effects of such exposures and their relationship to the short-term effects remain to be established. The present exp...

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity

PubMed Central

Finch, Natalie A.; Zasowski, Evan J.; Murray, Kyle P.; Mynatt, Ryan P.; Zhao, Jing J.; Yost, Raymond; Pogue, Jason M.

2017-01-01

ABSTRACT Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC24) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure. PMID:28923869

Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kleiman, Norman Jay

The lens of the eye is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiationmore » exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining radiosensitivity. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of radiosensitivity and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9, influence cataract development and thus radiosensitivity. These observations have direct applicability to various human populations including accidentally exposed individuals, interventional medical workers, astronauts and nuclear plant workers.« less

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity.

PubMed

Finch, Natalie A; Zasowski, Evan J; Murray, Kyle P; Mynatt, Ryan P; Zhao, Jing J; Yost, Raymond; Pogue, Jason M; Rybak, Michael J

2017-12-01

Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC 24 ) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC 24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC 24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure. Copyright © 2017 American Society for Microbiology.

Solar ultraviolet doses and vitamin D in a northern mid-latitude.

PubMed

Serrano, Maria-Antonia; Cañada, Javier; Moreno, Juan Carlos; Gurrea, Gonzalo

2017-01-01

Solar ultraviolet (UV) radiation is one of the most important factors in the development of skin cancer in human, solar erythema and skin aging. Nevertheless, numerous studies have shown the benefits of UV solar radiation in moderate doses, such as the reduction of blood pressure and mental health, treatment of various diseases, and the synthesis of vitamin D in the skin. This paper analyses data from solar ultraviolet erythemal (UVER) irradiance in W/m 2 measured in a northern mid-latitude as Valencia (Spain) for the period 2003-2010. To estimate effective solar UV radiation in the production of vitamin D (UVD) we used the relationship proposed by McKenzie et al. (2009). It was obtained for one month for each season the minimum exposure time needed around solar noon and at 9 UTC and 15 UTC (Coordinated Universal Time) to obtain the recommended daily dose of 1000IU. Also, it has been calculated time for erythema induction around solar noon for the same months. The median UVER daily dose during the summer months was 4000J/m 2 day, and 700J/m 2 day in winter. With regard to UVD, the median UVD daily dose in summer season was 7700J/m 2 day, and in winter it was 1000J/m 2 day. Around noon in January it takes more than two hours of solar exposure to obtain the recommended daily dose of vitamin D, whereas the rest of the year range between 7min on July and 31min on October. For the same months around noon, exposure times to produce erythema were obtained, these being of higher value to the previous. The results show that it is difficult to obtain the recommended vitamin D doses in winter in a northern mid-latitude, as the human body is almost entirely covered in this season. Copyright © 2016 Elsevier B.V. All rights reserved.

Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC*

PubMed Central

Karschner, Erin L.; Schwope, David M.; Schwilke, Eugene W.; Goodwin, Robert S.; Kelly, Deanna L.; Gorelick, David A.; Huestis, Marilyn A.

2012-01-01

Background Determining time since last cannabis/Δ9-tetrahydrocannabinol (THC) exposure is important in clinical, workplace, and forensic settings. Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P) ratio. No studies previously evaluated predictive models utilizing empirically-derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic THC dosing. Methods Ten male chronic, daily cannabis smokers received escalating around-the-clock oral THC (40-120 mg daily) for 8 days. Cannabinoids were quantified in whole blood and plasma by two-dimensional gas chromatography-mass spectrometry. Results Maximum whole blood THC occurred 3.0 h after the first oral THC dose and 103.5 h (4.3 days) during multiple THC dosing. Median WB/P ratios were THC 0.63 (n=196), 11-hydroxy-THC 0.60 (n=189), and 11-nor-9-carboxy-THC (THCCOOH) 0.55 (n=200). Predictive models utilizing these WB/P ratios accurately estimated last cannabis exposure in 96% and 100% of specimens collected within 1-5 h after a single oral THC dose and throughout multiple dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5 h after the last THC dose, respectively. Conclusions Predictive models estimating time since last cannabis intake from whole blood and plasma cannabinoid concentrations were inaccurate during abstinence, but highly accurate during active THC dosing. THC redistribution from large cannabinoid body stores and high circulating THCCOOH concentrations create different pharmacokinetic profiles than those in less than daily cannabis smokers that were used to derive the models. Thus, the models do not accurately predict time of last THC intake in individuals consuming THC daily. PMID:22464363

Longitudinal study of radiation exposure in computed tomography with an in-house developed dose monitoring system

NASA Astrophysics Data System (ADS)

Renger, Bernhard; Rummeny, Ernst J.; Noël, Peter B.

2013-03-01

During the last decades, the reduction of radiation exposure especially in diagnostic computed tomography is one of the most explored topics. In the same time, it seems challenging to quantify the long-term clinical dose reduction with regard to new hardware as well as software solutions. To overcome this challenge, we developed a Dose Monitoring System (DMS), which collects information from PACS, RIS, MPPS and structured reports. The integration of all sources overcomes the weaknesses of single systems. To gather all possible information, we integrated an optical character recognition system to extract, for example, information from the CT-dose-report. All collected data are transferred to a database for further evaluation, e.g., for calculations of effective as well as organ doses. The DMS provides a single database for tracking all essential study and patient specific information across different modality as well as different vendors. As an initial study, we longitudinally investigated the dose reduction in CT examination when employing a noise-suppressing reconstruction algorithm. For this examination type a significant long-term reduction in radiation exposure is reported, when comparing to a CT-system with standard reconstruction. In summary our DMS tool not only enables us to track radiation exposure on daily bases but further enables to analyses the long term effect of new dose saving strategies. In the future the statistical analyses of all retrospective data, which are available in a modern imaging department, will provide a unique overview of advances in reduction of radiation exposure.

Methodologies for the quantitative estimation of toxicant dose to cigarette smokers using physical, chemical and bioanalytical data

PubMed Central

McAughey, John; Shepperd, Christopher J.

2013-01-01

Methodologies have been developed, described and demonstrated that convert mouth exposure estimates of cigarette smoke constituents to dose by accounting for smoke spilled from the mouth prior to inhalation (mouth-spill (MS)) and the respiratory retention (RR) during the inhalation cycle. The methodologies are applicable to just about any chemical compound in cigarette smoke that can be measured analytically and can be used with ambulatory population studies. Conversion of exposure to dose improves the relevancy for risk assessment paradigms. Except for urinary nicotine plus metabolites, biomarkers generally do not provide quantitative exposure or dose estimates. In addition, many smoke constituents have no reliable biomarkers. We describe methods to estimate the RR of chemical compounds in smoke based on their vapor pressure (VP) and to estimate the MS for a given subject. Data from two clinical studies were used to demonstrate dose estimation for 13 compounds, of which only 3 have urinary biomarkers. Compounds with VP > 10−5 Pa generally have RRs of 88% or greater, which do not vary appreciably with inhalation volume (IV). Compounds with VP < 10−7 Pa generally have RRs dependent on IV and lung exposure time. For MS, mean subject values from both studies were slightly greater than 30%. For constituents with urinary biomarkers, correlations with the calculated dose were significantly improved over correlations with mouth exposure. Of toxicological importance is that the dose correlations provide an estimate of the metabolic conversion of a constituent to its respective biomarker. PMID:23742081

Accounting for patient size in the optimization of dose and image quality of pelvis cone beam CT protocols on the Varian OBI system.

PubMed

Wood, Tim J; Moore, Craig S; Horsfield, Carl J; Saunderson, John R; Beavis, Andrew W

2015-01-01

The purpose of this study was to develop size-based radiotherapy kilovoltage cone beam CT (CBCT) protocols for the pelvis. Image noise was measured in an elliptical phantom of varying size for a range of exposure factors. Based on a previously defined "small pelvis" reference patient and CBCT protocol, appropriate exposure factors for small, medium, large and extra-large patients were derived which approximate the image noise behaviour observed on a Philips CT scanner (Philips Medical Systems, Best, Netherlands) with automatic exposure control (AEC). Selection criteria, based on maximum tube current-time product per rotation selected during the radiotherapy treatment planning scan, were derived based on an audit of patient size. It has been demonstrated that 110 kVp yields acceptable image noise for reduced patient dose in pelvic CBCT scans of small, medium and large patients, when compared with manufacturer's default settings (125 kVp). Conversely, extra-large patients require increased exposure factors to give acceptable images. 57% of patients in the local population now receive much lower radiation doses, whereas 13% require higher doses (but now yield acceptable images). The implementation of size-based exposure protocols has significantly reduced radiation dose to the majority of patients with no negative impact on image quality. Increased doses are required on the largest patients to give adequate image quality. The development of size-based CBCT protocols that use the planning CT scan (with AEC) to determine which protocol is appropriate ensures adequate image quality whilst minimizing patient radiation dose.

Population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children with tuberculosis: in silico evaluation of currently recommended doses.

PubMed

Zvada, Simbarashe P; Denti, Paolo; Donald, Peter R; Schaaf, H Simon; Thee, Stephanie; Seddon, James A; Seifart, Heiner I; Smith, Peter J; McIlleron, Helen M; Simonsson, Ulrika S H

2014-05-01

To describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children and evaluate the adequacy of steady-state exposures. We used previously published data for 76 South African children with tuberculosis to describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid. Monte Carlo simulations were used to predict steady-state exposures in children following doses in fixed-dose combination tablets in accordance with the revised guidelines. Reference exposures were derived from an ethnically similar adult population with tuberculosis taking currently recommended doses. The final models included allometric scaling of clearance and volume of distribution using body weight. Maturation was included for clearance of isoniazid and clearance and absorption transit time of rifampicin. For a 2-year-old child weighing 12.5 kg, the estimated typical oral clearances of rifampicin and pyrazinamide were 8.15 and 1.08 L/h, respectively. Isoniazid typical oral clearance (adjusted for bioavailability) was predicted to be 4.44, 11.6 and 14.6 L/h for slow, intermediate and fast acetylators, respectively. Higher oral clearance values in intermediate and fast acetylators also resulted from 23% lower bioavailability compared with slow acetylators. Simulations based on our models suggest that with the new WHO dosing guidelines and utilizing available paediatric fixed-dose combinations, children will receive adequate rifampicin exposures when compared with adults, but with a larger degree of variability. However, pyrazinamide and isoniazid exposures in many children will be lower than in adults. Further studies are needed to confirm these findings in children administered the revised dosages and to optimize pragmatic approaches to dosing.

Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

PubMed Central

2012-01-01

Background According to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906), the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review. Results Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of < 200 mSv, but with head exposure which may (in absence of protection) arrive at a head equivalent dose of 1 to 3 Sv after a professional lifetime (corresponding to a brain equivalent dose around 500 mSv). Conclusions At this point, a systematic assessment of brain (cancer and non-cancer) effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed. PMID:22540409

Prospective study of direct radiation exposure measurements for family members living with patients with prostate (125)I seed implantation: Evidence of radiation safety.

PubMed

Hanada, Takashi; Yorozu, Atsunori; Shinya, Yukiko; Kuroiwa, Nobuko; Ohashi, Toshio; Saito, Shiro; Shigematsu, Naoyuki

2016-01-01

To broaden the current understanding of radiation exposure and risk and to provide concrete evidence of radiation safety related to (125)I seed implantation. Direct radiation exposure measurements were obtained from dosimeters provided to 25 patients who underwent (125)I seed implantation, along with their family members. The estimated lifetime exposure dose and the precaution time for holding children near the patient's chest were calculated in two study periods. During the first and second study period, the mean estimated lifetime exposure doses were, respectively, 7.61 (range: 0.45, 20.21) mSv and 6.84 (range: 0.41, 19.20) mSv for patients, and 0.19 (range: 0.02, 0.54) mSv and 0.25 (range: 0.04, 1.00) mSv for family members. The mean ratios of first and second period measurements were 1.05 (range: 0.44, 3.18) for patients and 1.82 (range: 0.21, 7.04) for family members. The corresponding absolute differences between first and second period measurements were -0.77 (range: -11.40, 7.63) mSv and 0.06 (range: -0.26, 0.79) mSv, respectively. Assuming a dose limit of 1 mSv, the precaution times for holding a child every day of the first and second periods were 250.9 (range: 71.3, 849.4) min and 275.2 (range: 75.0, 883.4) min, respectively. Assuming a dose limit of 0.5 mSv, the corresponding precaution times were 179.0 (range: 35.6, 811.5) min and 178.9 (range: 37.5, 1131.8) min, respectively. Our study demonstrated low radiation exposures to family members of patients undergoing (125)I prostate implantation. It was clear that (125)I seed implantation did not pose a threat to the safety of family members. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

A comprehensive dose reconstruction methodology for former rocketdyne/atomics international radiation workers.

PubMed

Boice, John D; Leggett, Richard W; Ellis, Elizabeth Dupree; Wallace, Phillip W; Mumma, Michael; Cohen, Sarah S; Brill, A Bertrand; Chadda, Bandana; Boecker, Bruce B; Yoder, R Craig; Eckerman, Keith F

2006-05-01

Incomplete radiation exposure histories, inadequate treatment of internally deposited radionuclides, and failure to account for neutron exposures can be important uncertainties in epidemiologic studies of radiation workers. Organ-specific doses from lifetime occupational exposures and radionuclide intakes were estimated for an epidemiologic study of 5,801 Rocketdyne/Atomics International (AI) radiation workers engaged in nuclear technologies between 1948 and 1999. The entire workforce of 46,970 Rocketdyne/AI employees was identified from 35,042 Kardex work histories cards, 26,136 electronic personnel listings, and 14,189 radiation folders containing individual exposure histories. To obtain prior and subsequent occupational exposure information, the roster of all workers was matched against nationwide dosimetry files from the Department of Energy, the Nuclear Regulatory Commission, the Landauer dosimetry company, the U.S. Army, and the U.S. Air Force. Dosimetry files of other worker studies were also accessed. Computation of organ doses from radionuclide intakes was complicated by the diversity of bioassay data collected over a 40-y period (urine and fecal samples, lung counts, whole-body counts, nasal smears, and wound and incident reports) and the variety of radionuclides with documented intake including isotopes of uranium, plutonium, americium, calcium, cesium, cerium, zirconium, thorium, polonium, promethium, iodine, zinc, strontium, and hydrogen (tritium). Over 30,000 individual bioassay measurements, recorded on 11 different bioassay forms, were abstracted. The bioassay data were evaluated using ICRP biokinetic models recommended in current or upcoming ICRP documents (modified for one inhaled material to reflect site-specific information) to estimate annual doses for 16 organs or tissues taking into account time of exposure, type of radionuclide, and excretion patterns. Detailed internal exposure scenarios were developed and annual internal doses were derived on a case-by-case basis for workers with committed equivalent doses indicated by screening criteria to be greater than 10 mSv to the organ with the highest internal dose. Overall, 5,801 workers were monitored for radiation at Rocketdyne/AI: 5,743 for external exposure and 2,232 for internal intakes of radionuclides; 41,169 workers were not monitored for radiation. The mean cumulative external dose based on Rocketdyne/AI records alone was 10.0 mSv, and the dose distribution was highly skewed with most workers experiencing low cumulative doses and only a few with high doses (maximum 500 mSv). Only 45 workers received greater than 200 mSv while employed at Rocketdyne/AI. However, nearly 32% (or 1,833) of the Rocketdyne/AI workers had been monitored for radiation at other nuclear facilities and incorporation of these doses increased the mean dose to 13.5 mSv (maximum 1,005 mSv) and the number of workers with >200 mSv to 69. For a small number of workers (n=292), lung doses from internal radionuclide intakes were relatively high (mean 106 mSv; maximum 3,560 mSv) and increased the overall population mean dose to 19.0 mSv and the number of workers with lung dose>200 mSv to 109. Nearly 10% of the radiation workers (584) were monitored for neutron exposures (mean 1.2 mSv) at Rocketdyne/AI, and another 2% were monitored for neutron exposures elsewhere. Interestingly, 1,477 workers not monitored for radiation at Rocketdyne/AI (3.6%) were found to have worn dosimeters at other nuclear facilities (mean external dose of 2.6 mSv, maximum 188 mSv). Without considering all sources of occupational exposure, an incorrect characterization of worker exposure would have occurred with the potential to bias epidemiologic results. For these pioneering workers in the nuclear industry, 26.5% of their total occupational dose (collective dose) was received at other facilities both prior to and after employment at Rocketdyne/AI. In addition, a small number of workers monitored for internal radionuclides contributed disproportionately to the number of workers with high lung doses. Although nearly 12% of radiation workers had been monitored for neutron exposures during their career, the cumulative dose levels were small in comparison with other external and internal exposure. Risk estimates based on nuclear worker data must be interpreted cautiously if internally deposited radionuclides and occupational doses received elsewhere are not considered.

Metabonomic analysis of urine from rats after low-dose exposure to 3-chloro-1,2-propanediol using UPLC-MS.

PubMed

Liu, Liyan; He, Yujie; Lu, Huimin; Wang, Maoqing; Sun, Changhao; Na, Lixin; Li, Ying

2013-05-15

To study the toxic effect of chronic exposure to 3-chloro-1,2-propanediol (3-MCPD) at low doses, a metabonomics approach based on ultrahigh-performance liquid chromatography and quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was performed. Two different doses of 3-MCPD (1.1 and 5.5mg/kg bw/d) were administered to Wistar rats for 120 days (1.1mg/kg bw/d: lowest observed adverse effect level [LOAEL]). The metabolite profiles and biochemical parameters were obtained at five time points after treatment. For the 3-MCPD-treated groups, a significant change in urinary N-acetyl-β-d-glucosaminidase and β-d-galactosidase was detected on day 90, while some biomarkers based on the metabonomics, such as N-acetylneuraminic acid, N-acetyl-l-tyrosine, and gulonic acid, were detected on day 30. These results suggest that these biomarkers changed more sensitively and earlier than conventional biochemical parameters and were thus considered early and sensitive biomarkers of exposure to 3-MCPD; these biomarkers provide more information on toxicity than conventional biochemical parameters. These results might be helpful to investigate the toxic mechanisms of 3-MCPD and provide a scientific basis for assessing the effect of chronic exposure to low-dose 3-MCPD on human health. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Monitoring exposure to atomic bomb radiation by somatic mutation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akiyama, Mitoshi; Kyoizumi, Seishi; Kusunoki, Yoichiro

Atomic bomb survivors are a population suitable for studying the relationship between somatic mutation and cancer risk because their exposure doses are relatively well known and their dose responses in terms of cancer risk have also been thoroughly studied. An analysis has been made of erythrocyte glycophorin A (GPA) gene mutations in 1,226 atomic bomb survivors in Hiroshima and Nagasaki. The GPA mutation frequency (Mf) increased slightly but significantly with age at the time of measurement and with the number of cigarettes smoked. After adjustment for the effect of smoking, the Mf was significantly higher in males than in femalesmore » and higher in Hiroshima than in Nagasaki. All of these characteristics of the background GPA Mf were in accord with those of solid tumor incidence obtained from an earlier epidemiological study of A-bomb survivors. Analysis of the dose effect on Mf revealed the doubling dose to be about 1.20 Sv and the minimum dose for detection of a significant increase to be about 0.24 Sv. No significant dose effect for difference in sex, city, or age at the time of bombing was observed. Interestingly, the doubling dose for the GPA Mf approximated that for solid cancer incidence (1.59 Sv). And the minimum dose for detection was not inconsistent with the data for solid cancer incidence. The dose effect was significantly higher in those diagnosed with cancer before or after measurement than in those without a history of cancer. These findings are consistent with the hypothesis that somatic mutations are the main cause of excess cancer risk from radiation exposure. 27 refs., 2 figs.« less

The validated sun exposure questionnaire: association of objective and subjective measures of sun exposure in a Danish population-based sample.

PubMed

Køster, B; Søndergaard, J; Nielsen, J B; Allen, M; Olsen, A; Bentzen, J

2017-02-01

Few questionnaires used in monitoring sun-related behaviour have been tested for validity. We established the criteria validity of a questionnaire developed for monitoring population sun-related behaviour. During May-August 2013, 664 Danes wore a personal electronic ultraviolet radiation (UVR) dosimeter for 1 week that measured their outdoor time and dose of erythemal UVR exposure. In the following week, they answered a questionnaire on their sun-related behaviour in the measurement week. Outdoor time measured by dosimetry correlated strongly with both outdoor time and the developed exposure scale measured in the questionnaire. Exposure measured in standard erythema dose (SED) by dosimetry correlated strongly with the exposure scale. In a linear regression model of UVR (SED) received, 41% of the variation was explained by skin type, age, week of participation and exposure scale, with exposure scale as the main contributor. The weekly sunburn fraction correlated strongly with the number of ambient sun hours (r = 0·73, P < 0·001). This criteria-validated questionnaire provides evidence of the exposure that the questionnaire aimed to measure. The evidence provided showed a strong link between the objectively measured behaviour and the behaviour measured by this survey construct. The questionnaire is the first validated tool to measure the UVR exposure in a national population-based sample. © 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Radiation Exposure and Health Effects – is it Time to Reassess the Real Consequences?

PubMed Central

Thomas, G.A.; Symonds, P.

2017-01-01

Our acceptance of exposure to radiation is somewhat schizophrenic. We accept that the use of high doses of radiation is still one of the most valuable weapons in our fight against cancer, and believe that bathing in radioactive spas is beneficial. On the other hand, as a species, we are fearful of exposure to man-made radiation as a result of accidents related to power generation, even though we understand that the doses are orders of magnitude lower than those we use everyday in medicine. The 70th anniversary of the detonation of the atomic bombs in Hiroshima and Nagasaki was marked in 2015. The 30th anniversary of the Chernobyl nuclear power plant accident will be marked in April 2016. March 2016 also sees the fifth anniversary of the accident at the Fukushima nuclear power plant. Perhaps now is an opportune time to assess whether we are right to be fearful of the effects of low doses of radiation, or whether actions taken because of our fear of radiation actually cause a greater detriment to health than the direct effect of radiation exposure. PMID:26880062

Effects of an acute dose of gamma radiation exposure on stem diameter growth, carbon gain, and biomass partitioning in Helianthus annuus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thiede, M.E.

1988-05-25

Nineteen-day-old dwarf sunflower plants (Helianthus annuus, variety NK894) received a variable dose (0-40 Gy) from a cobalt-60 gamma source. A very sensitive stem monitoring device, developed at Battelle's Pacific Northwest Laboratories, Richland, Washington was used to measure real-time changes in stem diameter. Exposure of plants caused a significant reduction in stem growth and root biomass. Doses as low as 5 Gy resulted in a significant increase in leaf density, suggesting that nonreversible morphological growth changes could be induced by very low doses of radiation. Carbohydrate analysis of 40-Gy irradiated plants demonstrated significantly more starch content in leaves and significantly lessmore » starch content in stems 18 days after exposure than did control plants. In contrast, the carbohydrate content in roots of 40-Gy irradiated plants were not significantly different from unirradiated plants 18 days after exposure. These results indicate that radiation either decreased phloem transport or reduced the availability of sugar reducing enzymes in irradiated plants. 44 refs., 12 figs.« less

Evaluation of internal alpha radiation exposure and subsequent infertility among a cohort of women formerly employed in the radium dial industry.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schieve, L. A.; Davis, F.; Roeske, J.

1997-02-01

This study examined the effect of internal exposure to {alpha}-particle radiation on subsequent fertility among women employed in the radium dial industry prior to 1930, when appreciable amounts of radium were often ingested through the practice of pointing the paint brush with the lips. The analysis was limited to women for whom a radium body burden measurement had been obtained and who were married prior to age 45 (n=603). Internal radiation dose to the ovary was calculated based on initial intakes of radium-226 and radium-228, average ovarian mass, number and energy of {alpha} particles emitted, fraction of energy absorbed withmore » in the ovary, effective retention integrals and estimated photon irradiation. Time between marriage and pregnancy, number of pregnancies and number of live births served as surrogates for fertility. Radiation appeared to have no effect on fertility at estimated cumulative ovarian dose equivalents below 5 Sv; above this dose, however, statistically significant declines in both number of pregnancies and live births were observed. These trends persisted after multivariable adjustment for potential confounding variables and after exclusion of subjects contributing a potential classification or selection bias to the study. Additionally, the high-dose group experienced fewer live births than would have been expected based on population rates. There were no differences in time to first pregnancy between high- and low-dose groups. These results are consistent with earlier studies of {gamma}-ray exposures and suggest that exposure to high doses of radiation from internally deposited radium reduces fertility rather than inducing sterility.« less

Buccal mucosa micronuclei counts in relation to exposure to low dose-rate radiation from the Chornobyl nuclear accident and other medical and occupational radiation exposures.

PubMed

Bazyka, D; Finch, S C; Ilienko, I M; Lyaskivska, O; Dyagil, I; Trotsiuk, N; Gudzenko, N; Chumak, V V; Walsh, K M; Wiemels, J; Little, M P; Zablotska, L B

2017-06-23

Ionizing radiation is a well-known carcinogen. Chromosome aberrations, and in particular micronuclei represent an early biological predictor of cancer risk. There are well-documented associations of micronuclei with ionizing radiation dose in some radiation-exposed groups, although not all. That associations are not seen in all radiation-exposed groups may be because cells with micronuclei will not generally pass through mitosis, so that radiation-induced micronuclei decay, generally within a few years after exposure. Buccal samples from a group of 111 male workers in Ukraine exposed to ionizing radiation during the cleanup activities at the Chornobyl nuclear power plant were studied. Samples were taken between 12 and 18 years after their last radiation exposure from the Chornobyl cleanup. The frequency of binucleated micronuclei was analyzed in relation to estimated bone marrow dose from the cleanup activities along with a number of environmental/occupational risk factors using Poisson regression adjusted for overdispersion. Among the 105 persons without a previous cancer diagnosis, the mean Chornobyl-related dose was 59.5 mSv (range 0-748.4 mSv). There was a borderline significant increase in micronuclei frequency among those reporting work as an industrial radiographer compared with all others, with a relative risk of 6.19 (95% CI 0.90, 31.08, 2-sided p = 0.0729), although this was based on a single person. There was a borderline significant positive radiation dose response for micronuclei frequency with increase in micronuclei per 1000 scored cells per Gy of 3.03 (95% CI -0.78, 7.65, 2-sided p = 0.1170), and a borderline significant reduction of excess relative MN prevalence with increasing time since last exposure (p = 0.0949). There was a significant (p = 0.0388) reduction in MN prevalence associated with bone X-ray exposure, but no significant trend (p = 0.3845) of MN prevalence with numbers of bone X-ray procedures. There are indications of increasing trends of micronuclei prevalence with Chornobyl-cleanup-associated dose, and indications of reduction in radiation-associated excess prevalence of micronuclei with time after exposure. There are also indications of substantially increased micronuclei associated with work as an industrial radiographer. This analysis adds to the understanding of the long-term effects of low-dose radiation exposures on relevant cellular structures and methods appropriate for long-term radiation biodosimetry.

Modeling the Prodromal Effects and Performance Reduction of Astronauts from Exposure to Large Solar Particle Events

NASA Technical Reports Server (NTRS)

Hu, S.; Kim, M. Y.; McClellan, G. E.; Nikjoo, H.; Cucinotta, F. A.

2007-01-01

In space exploration outside the Earth's geomagnetic field, radiation exposure from solar particle events (SPE) presents a health concern for astronauts, that could impair their performance and result in possibility of failure of the mission. Acute risks are especially of concern during spacewalks on the lunar surface because of the rapid onset of SPE's and science goals that involve long distances to crew habitats. Thus assessing the potential of early radiation effect under such adverse conditions is of prime importance. Here we present a biologic based mathematical model which describes the dose and time-dependent early human responses to ionizing radiation. We examine the possible early effects on crew behind various shielding materials from exposure to some historical large SPEs on the lunar and Mars surfaces. The doses and dose rates were calculated using the BRYNTRN code (Kim, M.Y, Hu, X, and Cucinotta, F.A, Effect of Shielding Materials from SPEs on the Lunar and Mars Surface, AIAA Space 2005, paper number AIAA-2005-6653, Long Beach, CA, August 30-September 1, 2005) and the hazard of the early radiation effects and performance reduction were calculated using the RIPD code (Anno, G.H, McClellan, G.E., Dore, M.A, Protracted Radiation-Induced Performance Decrement, Volume 1 Model Development,1996, Defense Nuclear Agency: Alexandria VA). Based on model assumptions we show that exposure to these historical SPEs do cause early effects to crew members and impair their performance if effective shielding and medical countermeasure tactics are not provided. The calculations show multiple occurrence of large SPEs in a short period of time significantly increase the severity of early illness, however early death from failure of the hematopoietic system is very unlikely because of the dose-rate and dose heterogeneity of SPEs. Results from these types of calculations will be a guide in design of protection systems and medical response strategy for astronauts in case of exposure to high dose irradiation during future space missions.

Risk of eye lens radiation exposure for members of the public.

PubMed

Chevallier, M-A; Rannou, A; Villagrasa, C; Clairand, I

2016-01-01

In 2011, the International Commission on Radiological Protection (ICRP) reviewed its recommendation concerning the equivalent dose limit for the eye lens, lowering it to 20 mSv in a year, for occupational exposure in planned exposure situations. The ICRP's statement does not contain any explicit recommendations regarding the organ dose limit for the eye lens for public exposure. For the moment, no change is proposed. But, to be coherent in the overall approach, the current equivalent limit for the public might be lowered. A similar yardstick than in the former recommendation may be used, that is to say a reduction of 10 times lower than that for occupational exposure. In this context, additional data on potential scenarios for public exposure of the eye lens are necessary. This paper, mainly based on a literature study, aims to provide, as far as possible, an exhaustive list of the situations in which members of the public can be exposed at the level of the eye lens. Once these situations have been defined, some calculations, made to assess the associated doses to the eye lens, are presented. This literature study did not reveal any current situations where members of the public would receive significant radiation doses to the eye lens. Indeed, the situations in which the dose to the eye lens might reach around 1 mSv per year for the public are extremely rare. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of postnatal low-dose exposure to environmental chemicals on the gut microbiome in a rodent model.

PubMed

Hu, Jianzhong; Raikhel, Vincent; Gopalakrishnan, Kalpana; Fernandez-Hernandez, Heriberto; Lambertini, Luca; Manservisi, Fabiana; Falcioni, Laura; Bua, Luciano; Belpoggi, Fiorella; L Teitelbaum, Susan; Chen, Jia

2016-06-14

This proof-of-principle study examines whether postnatal, low-dose exposure to environmental chemicals modifies the composition of gut microbiome. Three chemicals that are widely used in personal care products-diethyl phthalate (DEP), methylparaben (MPB), triclosan (TCS)-and their mixture (MIX) were administered at doses comparable to human exposure to Sprague-Dawley rats from birth through adulthood. Fecal samples were collected at two time points: postnatal day (PND) 62 (adolescence) and PND 181 (adulthood). The gut microbiome was profiled by 16S ribosomal RNA gene sequencing, taxonomically assigned and assessed for diversity. Metagenomic profiling revealed that the low-dose chemical exposure resulted in significant changes in the overall bacterial composition, but in adolescent rats only. Specifically, the individual taxon relative abundance for Bacteroidetes (Prevotella) was increased while the relative abundance of Firmicutes (Bacilli) was reduced in all treated rats compared to controls. Increased abundance was observed for Elusimicrobia in DEP and MPB groups, Betaproteobacteria in MPB and MIX groups, and Deltaproteobacteria in TCS group. Surprisingly, these differences diminished by adulthood (PND 181) despite continuous exposure, suggesting that exposure to the environmental chemicals produced a more profound effect on the gut microbiome in adolescents. We also observed a small but consistent reduction in the bodyweight of exposed rats in adolescence, especially with DEP and MPB treatment (p < 0.05), which is consistent with our findings of a reduced Firmicutes/Bacteroidetes ratio at PND 62 in exposed rats. This study provides initial evidence that postnatal exposure to commonly used environmental chemicals at doses comparable to human exposure is capable of modifying the gut microbiota in adolescent rats; whether these changes lead to downstream health effects requires further investigation.

Biochemical responses and accumulation properties of long-chain perfluorinated compounds (PFOS/PFDA/PFOA) in juvenile chickens (Gallus gallus).

PubMed

Yeung, Leo W Y; Loi, Eva I H; Wong, Vicky Y Y; Guruge, Keerthi S; Yamanaka, Noriko; Tanimura, Nobuhiko; Hasegawa, Jun; Yamashita, Nobuyoshi; Miyazaki, Shigeru; Lam, Paul K S

2009-08-01

One-day-old male chickens were exposed via oral gavage to mixtures of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorodecanoate (PFDA) at either a low dose (0.1 mg/kg body weight [b.w.]) or a high dose (1.0 mg/kg b.w.), or a saline/ethanol vehicle control, three times a week for 3 weeks. After 3 weeks of exposure, half of the chicks were sacrificed and the other half were allowed to depurate for a further 3 weeks. No dose-dependent statistically significant differences in body/organ weights were observed among treatment and control groups after 3 weeks of exposure or after three 3 of depuration. Neither 15 histological nor 14 measured plasma biochemical parameters were significantly different in chicks from the exposed groups and vehicle controls. PFOS, PFDA, and PFOA concentrations in blood/liver/kidney samples were measured throughout the exposure and depuration periods at different time intervals. PFOS and PFDA accumulated at much higher concentrations than PFOA during the experimental periods. Interestingly, PFOS and PFDA accumulation patterns in the blood were similar during the exposure and depuration periods. The half-lives for each PFC at the 0.1 and 1.0 mg/kg doses were, respectively, approximately 15 and 17 days for PFOS, 11 and 16 days for PFDA, and 3.9 and 3.9 days for PFOA. PFDA accumulation in organs was greater than or similar to that of PFOS: the liver was the main target during exposure and the blood was the main reservoir during depuration. These results indicate that exposure to a 1.0-mg mixture of PFOS/PFDA/PFOA/kg b.w. has no adverse effect on juvenile chickens.

Hair analysis as a useful procedure for detection of vapour exposure to chemical warfare agents: simulation of sulphur mustard with methyl salicylate.

PubMed

Spiandore, Marie; Piram, Anne; Lacoste, Alexandre; Josse, Denis; Doumenq, Pierre

2014-06-01

Chemical warfare agents (CWA) are highly toxic compounds which have been produced to kill or hurt people during conflicts or terrorist attacks. Despite the fact that their use is strictly prohibited according to international convention, populations' exposure still recently occurred. Development of markers of exposure to CWA is necessary to distinguish exposed victims from unexposed ones. We present the first study of hair usage as passive sampler to assess contamination by chemicals in vapour form. This work presents more particularly the hair adsorption capacity for methyl salicylate used as a surrogate of the vesicant sulphur mustard. Chemical vapours toxicity through the respiratory route has historically been defined through Haber's law's concentration-time (Ct) product, and vapour exposure of hair to methyl salicylate was conducted with various times or doses of exposure in the range of incapacitating and lethal Ct products corresponding to sulphur mustard. Following exposure, extraction of methyl salicylate from hair was conducted by simple soaking in dichloromethane. Methyl salicylate could be detected on hair for vapour concentration corresponding to about one fifth of the sulphur mustard concentration that would kill 50% of exposed individuals (LCt50). The amount of methyl salicylate recovered from hair increased with time or dose of exposure. It showed a good correlation with the concentration-time product, suggesting that hair could be used like a passive sampler to assess vapour exposure to chemical compounds. It introduces great perspectives concerning the use of hair as a marker of exposure to CWA. Copyright © 2014 John Wiley & Sons, Ltd.

Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys

NASA Technical Reports Server (NTRS)

Lucas, J. N.; Hill, F. S.; Burk, C. E.; Cox, A. B.; Straume, T.

1996-01-01

Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys.

PubMed

Lucas, J N; Hill, F S; Burk, C E; Cox, A B; Straume, T

1996-09-01

Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

Lung Cancer Mortality (1950–1999) among Eldorado Uranium Workers: A Comparison of Models of Carcinogenesis and Empirical Excess Risk Models

PubMed Central

Eidemüller, Markus; Jacob, Peter; Lane, Rachel S. D.; Frost, Stanley E.; Zablotska, Lydia B.

2012-01-01

Lung cancer mortality after exposure to radon decay products (RDP) among 16,236 male Eldorado uranium workers was analyzed. Male workers from the Beaverlodge and Port Radium uranium mines and the Port Hope radium and uranium refinery and processing facility who were first employed between 1932 and 1980 were followed up from 1950 to 1999. A total of 618 lung cancer deaths were observed. The analysis compared the results of the biologically-based two-stage clonal expansion (TSCE) model to the empirical excess risk model. The spontaneous clonal expansion rate of pre-malignant cells was reduced at older ages under the assumptions of the TSCE model. Exposure to RDP was associated with increase in the clonal expansion rate during exposure but not afterwards. The increase was stronger for lower exposure rates. A radiation-induced bystander effect could be a possible explanation for such an exposure response. Results on excess risks were compared to a linear dose-response parametric excess risk model with attained age, time since exposure and dose rate as effect modifiers. In all models the excess relative risk decreased with increasing attained age, increasing time since exposure and increasing exposure rate. Large model uncertainties were found in particular for small exposure rates. PMID:22936975

Exposure to low-dose barium by drinking water causes hearing loss in mice.

PubMed

Ohgami, Nobutaka; Hori, Sohjiro; Ohgami, Kyoko; Tamura, Haruka; Tsuzuki, Toyonori; Ohnuma, Shoko; Kato, Masashi

2012-10-01

We continuously ingest barium as a general element by drinking water and foods in our daily life. Exposure to high-dose barium (>100mg/kg/day) has been shown to cause physiological impairments. Direct administration of barium to inner ears by vascular perfusion has been shown to cause physiological impairments in inner ears. However, the toxic influence of oral exposure to low-dose barium on hearing levels has not been clarified in vivo. We analyzed the toxic influence of oral exposure to low-dose barium on hearing levels and inner ears in mice. We orally administered barium at low doses of 0.14 and 1.4 mg/kg/day to wild-type ICR mice by drinking water. The doses are equivalent to and 10-fold higher than the limit level (0.7 mg/l) of WHO health-based guidelines for drinking water, respectively. After 2-week exposure, hearing levels were measured by auditory brain stem responses and inner ears were morphologically analyzed. After 2-month exposure, tissue distribution of barium was measured by inductively coupled plasma mass spectrometry. Low-dose barium in drinking water caused severe hearing loss in mice. Inner ears including inner and outer hair cells, stria vascularis and spiral ganglion neurons showed severe degeneration. The Barium-administered group showed significantly higher levels of barium in inner ears than those in the control group, while barium levels in bone did not show a significant difference between the two groups. Barium levels in other tissues including the cerebrum, cerebellum, heart, liver and kidney were undetectably low in both groups. Our results demonstrate for the first time that low-dose barium administered by drinking water specifically distributes to inner ears resulting in severe ototoxicity with degeneration of inner ears in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

The scientific jigsaw puzzle: Fitting the pieces of the low-level radiation debate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beyea, Jan

2012-05-01

Quantitative risk estimates from exposure to ionizing radiation are dominated by analysis of the one-time exposures received by the Japanese survivors at Hiroshima and Nagasaki. Three recent epidemiologic studies suggest that the risk from protracted exposure is no lower, and in fact may be higher, than from single exposures. There is near-universal acceptance that epidemiologic data demonstrates an excess risk of delayed cancer incidence above a dose of 0.1 sievert (Sv), which, for the average American, is equivalent to 40 years of unavoidable exposure from natural background radiation. Model fits, both parametric and nonparametric, to the atomic-bomb data support amore » linear no-threshold model, below 0.1 Sv. On the basis of biologic arguments, the scientific establishment in the United States and many other countries accepts this dose-model down to zero-dose, but there is spirited dissent. The dissent may be irrelevant for developed countries, given the increase in medical diagnostic radiation that has occurred in recent decades; a sizeable percentage of this population will receive cumulative doses from the medical profession in excess of 0.1 Sv, making talk of a threshold or other sublinear response below that dose moot for future releases from nuclear facilities or a dirty bomb. The risks from both medical diagnostic doses and nuclear accident doses can be computed using the linear dose-response model, with uncertainties assigned below 0.1 Sv in a way that captures alternative scientific hypotheses. Then, the important debate over low-level radiation exposures, namely planning for accident response and weighing benefits and risks of technologies, can proceed with less distraction. One of the biggest paradoxes in the low-level radiation debate is that an individual risk can be a minor concern, while the societal risk-the total delayed cancers in an exposed population-can be of major concern.« less

Photothermal damage is correlated to the delivery rate of time-integrated temperature

NASA Astrophysics Data System (ADS)

Denton, Michael L.; Noojin, Gary D.; Gamboa, B. Giovanna; Ahmed, Elharith M.; Rockwell, Benjamin A.

2016-03-01

Photothermal damage rate processes in biological tissues are usually characterized by a kinetics approach. This stems from experimental data that show how the transformation of a specified biological property of cells or biomolecule (plating efficiency for viability, change in birefringence, tensile strength, etc.) is dependent upon both time and temperature. However, kinetic methods require determination of kinetic rate constants and knowledge of substrate or product concentrations during the reaction. To better understand photothermal damage processes we have identified temperature histories of cultured retinal cells receiving minimum lethal thermal doses for a variety of laser and culture parameters. These "threshold" temperature histories are of interest because they inherently contain information regarding the fundamental thermal dose requirements for damage in individual cells. We introduce the notion of time-integrated temperature (Tint) as an accumulated thermal dose (ATD) with units of °C s. Damaging photothermal exposure raises the rate of ATD accumulation from that of the ambient (e.g. 37 °C) to one that correlates with cell death (e.g. 52 °C). The degree of rapid increase in ATD (ΔATD) during photothermal exposure depends strongly on the laser exposure duration and the ambient temperature.

Microarray analysis of miRNA expression profiles following whole body irradiation in a mouse model.

PubMed

Aryankalayil, Molykutty J; Chopra, Sunita; Makinde, Adeola; Eke, Iris; Levin, Joel; Shankavaram, Uma; MacMillan, Laurel; Vanpouille-Box, Claire; Demaria, Sandra; Coleman, C Norman

2018-06-19

Accidental exposure to life-threatening radiation in a nuclear event is a major concern; there is an enormous need for identifying biomarkers for radiation biodosimetry to triage populations and treat critically exposed individuals. To identify dose-differentiating miRNA signatures from whole blood samples of whole body irradiated mice. Mice were whole body irradiated with X-rays (2 Gy-15 Gy); blood was collected at various time-points post-exposure; total RNA was isolated; miRNA microarrays were performed; miRNAs differentially expressed in irradiated vs. unirradiated controls were identified; feature extraction and classification models were applied to predict dose-differentiating miRNA signature. We observed a time and dose responsive alteration in the expression levels of miRNAs. Maximum number of miRNAs were altered at 24-h and 48-h time-points post-irradiation. A 23-miRNA signature was identified using feature selection algorithms and classifier models. An inverse correlation in the expression level changes of miR-17 members, and their targets were observed in whole body irradiated mice and non-human primates. Whole blood-based miRNA expression signatures might be used for predicting radiation exposures in a mass casualty nuclear incident.

X-Ray-Induced Chromosome Aberrations in Mouse Dictyate Oocytes. II. Fractionation and Dose Rate Effects

PubMed Central

Brewen, J. G.; Payne, H. S.; Adler, I. D.

1977-01-01

Split-dose experiments were done on maturing dictyate oocytes to determine if the magnitude of the first dose influenced the "rejoining time" of radiation-induced chromosomal lesions. A total dose of 400r was split into various combinations with varying fractionation intervals. The data derived from analyzing interchanges indicate that there is no difference in the rejoining time whether the first dose was 100, 200, or 300r. It thus appears that the radiation dose in the ranges studied does not significantly alter the rate of repair of the chromosomal lesions. This conclusion is contrary to that which has been propounded to explain the nonlinear dose curves obtained for specific locus mutations. Chronic 60Co γ-ray exposures were given to female mice over an 8-day period. The exposures were delivered during the period of peak sensitivity, i.e., 8–16 days prior to ovulation. The doses given were 117, 240, 348, and 483r. The aberration yields observed were dramatically lower than for comparable doses of acute X rays even when the RBE of γ rays compared with X rays is taken into account. The large drop in yields at the low dose rates is interpreted as resulting from a large two-track component in the acute curve, and as being independent of effects on repair systems. PMID:604163

An 11-year review of levetiracetam ingestions in children less than 6 years of age.

PubMed

Lewis, J C; Albertson, T E; Walsh, M J

2014-11-01

Levetiracetam is a new anticonvulsant, which works to block high-voltage-activated Ca(++) channels in children, for partial-onset seizures. Reports of clinical experience with pediatric ingestions are minimal. The purpose of this study was to characterize the toxicity of accidental levetiracetam exposures in children less than 6 years of age. This was an 11-year retrospective observational case series of pediatric (< 6 years old) levetiracetam ingestions reported to a Poison Control System from 2002 to 2013. Case narratives were individually reviewed to collect desired information on exposure and clinical course. Inclusion criteria were levetiracetam as a single ingested medication, age less than 6 years, treatment in a health care facility, and followed to a known outcome. Eighty-two cases met inclusion criteria with 55% female patients and overall median age of 2.0 years (range: 1-60 months). The levetiracetam dose ingested was reported in 69 (84.1%) cases, with exact dose (median dose, 45.0 mg/kg; range, 10.5-1429 mg/kg) reported in 33 cases (40.2%). Of these, twenty-nine cases (88%) involved the oral solution formulation and 28 cases (85%) had unintentional therapeutic error as the cause of the exposure. No dose-response relationship was demonstrated; however, the odds of a levetiracetam-naive patient, (median dose, 26.9 mg/kg; N = 15) with an unintentional exposure, developing drowsiness or ataxia was 6 times that of a patient who was not naïve to levetiracetam (median dose, 70.1 mg/kg; N = 20) (Odds ratio [OR], 6.0; 95% confidence interval [CI], 1.03-35.91).Of the 82 cases, 17 (20.7%) developed untoward clinical effects of drowsiness and/or ataxia. Eighty patients (97.6%) were treated and discharged from the emergency department, and two patients (2.4%) were admitted. The two patients admitted included a two-month old who was accidentally given a dose 10 times that of her usual dose and a 3-year old who was lethargic on arrival to the hospital after ingestion of an unknown dose. Of all patients, 66 patients (80.5%) had no effect from the drug exposure. The medical outcome was considered to be minor in 15 cases (18.3%), and moderate in 1 case (1.2%). There were no cases with major outcomes and no deaths. Pediatric levetiracetam exposures were associated with few transient clinical effects. Poison Control Centers may wish to consider acuity of ingestion when developing send-in protocols.

Efficacy of RADPAD® protection drape in reducing radiation exposure to the primary operator during Transcatheter Aortic Valve Implantation (TAVI).

PubMed

Sharma, Divyesh; Ramsewak, Adesh; Manoharan, Ganesh; Spence, Mark S

2016-02-01

The efficacy of RADPAD® (a sterile, lead-free drape) has been demonstrated to reduce the scatter radiation to the primary operator during fluoroscopic procedures. However, the use of the RADPAD® during TAVI procedures has not been studied. Transcatheter aortic valve implantation (TAVI) is now an established treatment for patients with symptomatic severe aortic stenosis who are deemed inoperable or at high risk for conventional surgical aortic valve replacement (AVR). Consequently the radiation exposure to the patient and the interventional team from this procedure has become a matter of interest and importance. Methods to reduce radiation exposure to the interventional team during this procedure should be actively investigated. In this single center prospective study, we determined the radiation dose during this procedure and the efficacy of RADPAD® in reducing the radiation dose to the primary operator. Fifty consecutive patients due to undergo elective TAVI procedures were identified. Patients were randomly assigned to undergo the procedure with or without the use of a RADPAD® drape. There were 25 patients in each group and dosimetry was performed at the left eye level of the primary operator. The dosimeter was commenced at the start of the procedure, and the dose was recorded immediately after the end of the procedure. Fluoroscopy times and DAP were also recorded prospectively. Twenty-five patients underwent transfemoral TAVI using a RADPAD® and 25 with no-RADPAD®. The mean primary operator radiation dose was significantly lower in the RADPAD group at 14.8 mSv vs. 24.3 mSv in the no-RADPAD group (P=0.008). There was no significant difference in fluoroscopy times or dose-area products between the two patient groups. The dose to the primary operator relative to fluoroscopy time (RADPAD: slope=0.325; no RADPAD: slope=1.148; analysis of covariance F=7.47, P=0.009) and dose area product (RADPAD: slope=0.0007; no RADPAD: slope=0.002; analysis of covariance F=7.38; P=0.009) was smaller in the RADPAD group compared to no-RADPAD group. Use of a RADPAD® significantly reduces radiation exposure to the primary operator during TAVI procedures.

γ-H2AX responds to DNA damage induced by long-term exposure to combined low-dose-rate neutron and γ-ray radiation.

PubMed

Zhang, Junlin; He, Ying; Shen, Xianrong; Jiang, Dingwen; Wang, Qingrong; Liu, Qiong; Fang, Wen

2016-01-01

Risk estimates for low-dose radiation (LDR) remain controversial. The possible involvement of DNA repair-related genes in long-term low-dose-rate neutron-gamma radiation exposure is poorly understood. In this study, 60 rats were divided into control groups and irradiated groups, which were exposed to low-dose-rate n-γ combined radiation (LDCR) for 15, 30, or 60 days. The effects of different cumulative radiation doses on peripheral blood cell (PBC), subsets of T cells of peripheral blood lymphocytes (PBL) and DNA damage repair were investigated. Real-time PCR and immunoblot analyses were used to detect expression of DNA DSB-repair-related genes involved in the NHEJ pathway, such as Ku70 and Ku80, in PBL. The mRNA level of H2AX and the expression level of γ-H2AX were detected by real-time PCR, immunoblot, and flow cytometry. White blood cells (WBC) and platelets (PLT) of all ionizing radiation (IR) groups decreased significantly, while no difference was seen between the 30 day and 60 day exposure groups. The numbers of CD3(+), CD4(+) T cells and CD4(+)/CD8(+) in the PBL of IR groups were lower than in the control group. In the 30 day and 60 day exposure groups, CD8(+) T cells decreased significantly. Real-time PCR and immunoblot results showed no significant difference in the mRNA and protein expression of Ku70 and Ku80 between the control groups and IR groups. However, the mRNA of H2AX increased significantly, and there was a positive correlation with dose. There was no difference in the protein expression of γ-H2AX between 30 day and 60 day groups, which may help to explain the damage to PBL. In conclusion, PBL damage increased with cumulative dose, suggesting that γ-H2AX, but neither Ku70 nor Ku80, plays an important role in PBL impairment induced by LDCR. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Occupational exposure to radon for underground tourist routes in Poland: Doses to lung and the risk of developing lung cancer.

PubMed

Walczak, Katarzyna; Olszewski, Jerzy; Politański, Piotr; Zmyślony, Marek

2017-07-14

Radon concentrations for 31 Polish underground tourist routes were analyzed. The equivalent dose to the lung, the effective dose and the relative risk were calculated for employees of the analyzed routes on the grounds of information on radon concentrations, work time, etc. The relative risk for lung cancers was calculated using the Biological Effects of Ionizing Radiation (BEIR) VI Committee model. Equivalent doses to the lungs of workers were determined using the coefficients calculated by the Kendall and Smith. The conversion coefficient proposed by the International Atomic Energy Agency (IAEA) in the report No. 33 was used for estimating the effective doses. In 13 routes, the effective dose was found to be above 1 mSv/year, and in 3 routes, it exceeded 6 mSv/year. For 5 routes, the equivalent dose to lungs was higher than 100 mSv/year, and in 1 case it was as high as 490 mSv/year. In 22.6% of underground workplaces the risk of developing lung cancer among employees was about 2 times higher than that for the general population, and for 1 tourist route it was about 5 times higher. The geometric mean of the relative risk of lung cancer for all workers of underground tourist routes was 1.73 (95% confidence interval (CI): 1.6-1.87). Routes were divided into: caves, mines, post-military underground constructions and urban underground constructions. The difference between levels of the relative risk of developing lung cancer for all types of underground tourist routes was not found to be significant. If we include the professional group of the employees of underground tourist routes into the group of occupational exposure, the number of persons who are included in the Category A due to occupational exposure may increase by about 3/4. The professional group of the employees of underground tourist routes should be monitored for their exposure to radon. Int J Occup Med Environ Health 2017;30(5):687-694. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Evaluation of single-point sampling strategies for the estimation of moclobemide exposure in depressive patients.

PubMed

Ignjatovic, Anita Rakic; Miljkovic, Branislava; Todorovic, Dejan; Timotijevic, Ivana; Pokrajac, Milena

2011-05-01

Because moclobemide pharmacokinetics vary considerably among individuals, monitoring of plasma concentrations lends insight into its pharmacokinetic behavior and enhances its rational use in clinical practice. The aim of this study was to evaluate whether single concentration-time points could adequately predict moclobemide systemic exposure. Pharmacokinetic data (full 7-point pharmacokinetic profiles), obtained from 21 depressive inpatients receiving moclobemide (150 mg 3 times daily), were randomly split into development (n = 18) and validation (n = 16) sets. Correlations between the single concentration-time points and the area under the concentration-time curve within a 6-hour dosing interval at steady-state (AUC(0-6)) were assessed by linear regression analyses. The predictive performance of single-point sampling strategies was evaluated in the validation set by mean prediction error, mean absolute error, and root mean square error. Plasma concentrations in the absorption phase yielded unsatisfactory predictions of moclobemide AUC(0-6). The best estimation of AUC(0-6) was achieved from concentrations at 4 and 6 hours following dosing. As the most reliable surrogate for moclobemide systemic exposure, concentrations at 4 and 6 hours should be used instead of predose trough concentrations as an indicator of between-patient variability and a guide for dose adjustments in specific clinical situations.

PREDICTING THE RISKS OF NEUROTOXIC VOLATILE ORGANIC COMPOUNDS BASED ON TARGET TISSUE DOSE.

EPA Science Inventory

Quantitative exposure-dose-response models relate the external exposure of a substance to the dose in the target tissue, and then relate the target tissue dose to production of adverse outcomes. We developed exposure-dose-response models to describe the affects of acute exposure...

Low-dose x-ray tomography through a deep convolutional neural network

DOE PAGES

Yang, Xiaogang; De Andrade, Vincent; Scullin, William; ...

2018-02-07

Synchrotron-based X-ray tomography offers the potential of rapid large-scale reconstructions of the interiors of materials and biological tissue at fine resolution. However, for radiation sensitive samples, there remain fundamental trade-offs between damaging samples during longer acquisition times and reducing signals with shorter acquisition times. We present a deep convolutional neural network (CNN) method that increases the acquired X-ray tomographic signal by at least a factor of 10 during low-dose fast acquisition by improving the quality of recorded projections. Short exposure time projections enhanced with CNN show similar signal to noise ratios as compared with long exposure time projections and muchmore » lower noise and more structural information than low-dose fats acquisition without CNN. We optimized this approach using simulated samples and further validated on experimental nano-computed tomography data of radiation sensitive mouse brains acquired with a transmission X-ray microscopy. We demonstrate that automated algorithms can reliably trace brain structures in datasets collected with low dose-CNN. As a result, this method can be applied to other tomographic or scanning based X-ray imaging techniques and has great potential for studying faster dynamics in specimens.« less

Low-dose x-ray tomography through a deep convolutional neural network

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xiaogang; De Andrade, Vincent; Scullin, William

Synchrotron-based X-ray tomography offers the potential of rapid large-scale reconstructions of the interiors of materials and biological tissue at fine resolution. However, for radiation sensitive samples, there remain fundamental trade-offs between damaging samples during longer acquisition times and reducing signals with shorter acquisition times. We present a deep convolutional neural network (CNN) method that increases the acquired X-ray tomographic signal by at least a factor of 10 during low-dose fast acquisition by improving the quality of recorded projections. Short exposure time projections enhanced with CNN show similar signal to noise ratios as compared with long exposure time projections and muchmore » lower noise and more structural information than low-dose fats acquisition without CNN. We optimized this approach using simulated samples and further validated on experimental nano-computed tomography data of radiation sensitive mouse brains acquired with a transmission X-ray microscopy. We demonstrate that automated algorithms can reliably trace brain structures in datasets collected with low dose-CNN. As a result, this method can be applied to other tomographic or scanning based X-ray imaging techniques and has great potential for studying faster dynamics in specimens.« less

Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study

PubMed Central

Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

2017-01-01

After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)–4.29 mSv), 0.37 mSv (range: ND–3.61 mSv), 0.22 mSv (range: ND–1.44 mSv), 0.20 mSv (range: ND–1.87 mSv), and 0.17 mSv (range: ND–0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04–0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and temporal effects on reducing individual external doses. PMID:28235009

The mare reproductive loss syndrome and the eastern tent caterpillar: a toxicokinetic/statistical analysis with clinical, epidemiologic, and mechanistic implications.

PubMed

Sebastian, Manu; Gantz, Marie G; Tobin, Thomas; Harkins, J Daniel; Bosken, Jeffrey M; Hughes, Charlie; Harrison, Lenn R; Bernard, William V; Richter, Dana L; Fitzgerald, Terrence D

2003-01-01

During 2001, central Kentucky experienced acute transient epidemics of early and late fetal losses, pericarditis, and unilateral endophthalmitis, collectively referred to as mare reproductive loss syndrome (MRLS). A toxicokinetic/statistical analysis of experimental and field MRLS data was conducted using accelerated failure time (AFT) analysis of abortions following administration of Eastern tent caterpillars (ETCs; 100 or 50 g/day or 100 g of irradiated caterpillars/day) to late-term pregnant mares. In addition, 2001 late-term fetal loss field data were used in the analysis. Experimental data were fitted by AFT analysis at a high (P <.0001) significance. Times to first abortion ("lag time") and abortion rates were dose dependent. Lag times decreased and abortion rates increased exponentially with dose. Calculated dose x response data curves allow interpretation of abortion data in terms of "intubated ETC equivalents." Analysis suggested that field exposure to ETCs in 2001 in central Kentucky commenced on approximately April 27, was initially equivalent to approximately 5 g of intubated ETCs/day, and increased to approximately 30 g/day at the outbreak peak. This analysis accounts for many aspects of the epidemiology, clinical presentations, and manifestations of MRLS. It allows quantitative interpretation of experimental and field MRLS data and has implications for the basic mechanisms underlying MRLS. The results support suggestions that MRLS is caused by exposure to or ingestion of ETCs. The results also show that high levels of ETC exposure produce intense, focused outbreaks of MRLS, closely linked in time and place to dispersing ETCs, as occurred in central Kentucky in 2001. With less intense exposure, lag time is longer and abortions tend to spread out over time and may occur out of phase with ETC exposure, obscuring both diagnosis of this syndrome and the role of the caterpillars.

Bisphenol A alters early oogenesis and follicle formation in the fetal ovary of the rhesus monkey

PubMed Central

Hunt, Patricia A.; Lawson, Crystal; Gieske, Mary; Murdoch, Brenda; Smith, Helen; Marre, Alyssa; Hassold, Terry; VandeVoort, Catherine A.

2012-01-01

Widespread use of the endocrine disrupting chemical bisphenol A (BPA) in consumer products has resulted in nearly continuous human exposure. In rodents, low-dose exposures have been reported to adversely affect two distinct stages of oogenesis in the developing ovary: the events of prophase at the onset of meiosis in the fetal ovary and the formation of follicles in the perinatal ovary. Because these effects could influence the reproductive longevity and success of the exposed individual, we conducted studies in the rhesus monkey to determine whether BPA induces similar disturbances in the developing primate ovary. The routes and levels of human exposure are unclear; hence, two different exposure protocols were used: single daily oral doses and continuous exposure via subdermal implant. Our analyses of second trimester fetuses exposed at the time of meiotic onset suggest that, as in mice, BPA induces subtle disturbances in the prophase events that set the stage for chromosome segregation at the first meiotic division. Our analyses of third-trimester fetuses exposed to single daily oral doses during the time of follicle formation revealed an increase in multioocyte follicles analogous to that reported in rodents. However, two unique phenotypes were evident in continuously exposed animals: persistent unenclosed oocytes in the medullary region and small, nongrowing oocytes in secondary and antral follicles. Because effects on both stages of oogenesis were elicited using doses that yield circulating levels of BPA analogous to those reported in humans, these findings raise concerns for human reproductive health. PMID:23012422

Human Dose-Response Data for Francisella tularensis and a Dose- and Time-Dependent Mathematical Model of Early-Phase Fever Associated with Tularemia After Inhalation Exposure.

PubMed

McClellan, Gene; Coleman, Margaret; Crary, David; Thurman, Alec; Thran, Brandolyn

2018-04-25

Military health risk assessors, medical planners, operational planners, and defense system developers require knowledge of human responses to doses of biothreat agents to support force health protection and chemical, biological, radiological, nuclear (CBRN) defense missions. This article reviews extensive data from 118 human volunteers administered aerosols of the bacterial agent Francisella tularensis, strain Schu S4, which causes tularemia. The data set includes incidence of early-phase febrile illness following administration of well-characterized inhaled doses of F. tularensis. Supplemental data on human body temperature profiles over time available from de-identified case reports is also presented. A unified, logically consistent model of early-phase febrile illness is described as a lognormal dose-response function for febrile illness linked with a stochastic time profile of fever. Three parameters are estimated from the human data to describe the time profile: incubation period or onset time for fever; rise time of fever; and near-maximum body temperature. Inhaled dose-dependence and variability are characterized for each of the three parameters. These parameters enable a stochastic model for the response of an exposed population through incorporation of individual-by-individual variability by drawing random samples from the statistical distributions of these three parameters for each individual. This model provides risk assessors and medical decisionmakers reliable representations of the predicted health impacts of early-phase febrile illness for as long as one week after aerosol exposures of human populations to F. tularensis. © 2018 Society for Risk Analysis.

Persistent changes in neuronal structure and synaptic plasticity caused by proton irradiation.

PubMed

Parihar, Vipan K; Pasha, Junaid; Tran, Katherine K; Craver, Brianna M; Acharya, Munjal M; Limoli, Charles L

2015-03-01

Cranial radiotherapy is used routinely to control the growth of primary and secondary brain tumors, but often results in serious and debilitating cognitive dysfunction. In part due to the beneficial dose depth distributions that may spare normal tissue damage, the use of protons to treat CNS and other tumor types is rapidly gaining popularity. Astronauts exposed to lower doses of protons in the space radiation environment are also at risk for developing adverse CNS complications. To explore the consequences of whole body proton irradiation, mice were subjected to 0.1 and 1 Gy and analyzed for morphometric changes in hippocampal neurons 10 and 30 days following exposure. Significant dose-dependent reductions (~33 %) in dendritic complexity were found, when dendritic length, branching and area were analyzed 30 days after exposure. At equivalent doses and times, significant reductions in the number (~30 %) and density (50-75 %) of dendritic spines along hippocampal neurons of the dentate gyrus were also observed. Immature spines (filopodia, long) exhibited the greatest sensitivity (1.5- to 3-fold) to irradiation, while more mature spines (mushroom) were more resistant to changes over a 1-month post-irradiation timeframe. Irradiated granule cell neurons spanning the subfields of the dentate gyrus showed significant and dose-responsive reductions in synaptophysin expression, while the expression of postsynaptic density protein (PSD-95) was increased significantly. These findings corroborate our past work using photon irradiation, and demonstrate for the first time, dose-responsive changes in dendritic complexity, spine density and morphology and synaptic protein levels following exposure to low-dose whole body proton irradiation.

A study of the time of hospital discharge of differentiated thyroid cancer patients after receiving iodine-131 for thyroid remnant ablation treatment.

PubMed

Azizmohammadi, Zahra; Tabei, Faraj; Shafiei, Babak; Babaei, Ali Akbar; Jukandan, Seyed Mohsen Qutbi; Naghshine, Reza; Javadi, Hamid; Nabipour, Iraj; Assadi, Majid; Asli, Isa Neshandar

2013-01-01

The aim of this study was to measure the radiation exposure rate from differentiated thyroid carcinoma (DTC) patients who had received iodine-131 ((131)I) treatment, and to evaluate hospital discharge planning in relation to three different sets of regulations. We studied 100 patients, 78 females and 22 males, aged 13 to 79 years (mean 44.40±15.83 years) with DTC, in three Groups who were treated with 3.7, 5.5 or 7.4GBq of (131)I, respectively. The external whole-body dose rates following oral administration of (131)I were measured after each one of the first three hospitalization days. A multivariant linear analysis was performed, considering exposure rates as dependent variables to the administered dose for treatment, age, gender, regional and/or distant metastases, thyroglobulin (Tg), antibodies to Tg and thyroid remnant in the three dose groups. We found that the exposure rates after each of the three first days of hospitalization were 30, 50 and 70μSvh-1 at 1m. All our DTC patients had an acceptable dose rate on days 2 and 3 that allowed their hospital discharge. After only 1 day of hospitalization, just 3/11 cases showed not permissible exposure rates above 70μSvh-1. In conclusion, it is the opinion of the authors that after measuring the exposure rates, most treated, DTC patients could be discharged after only one day of hospitalization, even some of those treated with high doses of (131)I (7.4GBq). Patients, who received the higher doses of (131)I, should not be released before their individual exposure rate is measured.

DNA Damage Following Pulmonary Exposure by Instillation to Low Doses of Carbon Black (Printex 90) Nanoparticles in Mice

PubMed Central

Kyjovska, Zdenka O; Jacobsen, Nicklas R; Saber, Anne T; Bengtson, Stefan; Jackson, Petra; Wallin, Håkan; Vogel, Ulla

2015-01-01

We previously observed genotoxic effects of carbon black nanoparticles at low doses relative to the Danish Occupational Exposure Limit (3.5 mg/m3). Furthermore, DNA damage occurred in broncho-alveolar lavage (BAL) cells in the absence of inflammation, indicating that inflammation is not required for the genotoxic effects of carbon black. In this study, we investigated inflammatory and acute phase response in addition to genotoxic effects occurring following exposure to nanoparticulate carbon black (NPCB) at even lower doses. C57BL/6JBomTac mice were examined 1, 3, and 28 days after a single instillation of 0.67, 2, 6, and 162 µg Printex 90 NPCB and vehicle. Cellular composition and protein concentration was evaluated in BAL fluid as markers of inflammatory response and cell damage. DNA strand breaks in BAL cells, lung, and liver tissue were assessed using the alkaline comet assay. The pulmonary acute phase response was analyzed by Saa3 mRNA real-time quantitative PCR. Instillation of the low doses of NPCB induced a slight neutrophil influx one day after exposure. Pulmonary exposure to small doses of NPCB caused an increase in DNA strand breaks in BAL cells and lung tissue measured using the comet assay. We interpret the increased DNA strand breaks occurring following these low exposure doses of NPCB as DNA damage caused by primary genotoxicity in the absence of substantial inflammation, cell damage, and acute phase response. Environ. Mol. Mutagen. 56:41–49, 2015. © 2014 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society PMID:25042074

Arsenic in Drinking Water and Mortality for Cancer and Chronic Diseases in Central Italy, 1990-2010

PubMed Central

D’Ippoliti, Daniela; Santelli, Enrica; De Sario, Manuela; Scortichini, Matteo; Davoli, Marina; Michelozzi, Paola

2015-01-01

Background In several volcanic areas of Italy, arsenic levels exceed European regulatory limits (10 μg/L in drinking water). There is still uncertainty about health risks from arsenic at low-medium doses (<100 μg/L). Objectives A large population-based study using an administrative cohort of residents in the Viterbo province (Central Italy), chronically exposed to low-medium arsenic levels via drinking water, was investigated to evaluate the effects of a lifetime exposure to arsenic on mortality from cancers and chronic diseases. Methods The study population consisted of 165,609 residents of 17 municipalities, followed from 1990 until 2010. Average individual arsenic exposure at the first residence (AsI) was estimated through a space-time modeling approach using residential history and arsenic concentrations from water supply. A time-dependent Cumulative Arsenic dose Indicator (CAI) was calculated, accounting for daily water intake and exposure duration. Mortality Hazard Ratios (HR) were estimated by gender for different diseases using Cox proportional models, adjusting for individual and area-level confounders. A flexible non-parametric approach was used to investigate dose-response relationships. Results Mean AsI exposure was 19.3 μg/L, and average exposure duration was 39.5 years. Associations of AsI and CAI indicators with several diseases were found, with greatest risks found for lung cancer in both sexes (HR = 2.61 males; HR = 2.09 females), myocardial infarction, peripheral arterial disease and COPD in males (HR = 2.94; HR = 2.44; HR = 2.54 respectively) and diabetes in females (HR = 2.56). For lung cancer and cardiovascular diseases dose-response relationship is modelled by piecewise linear functions revealing effects even for doses lower than 10 μg/L, and no threshold dose value was identified as safe for health. Conclusions Results provide new evidence for risk assessment of low-medium concentrations of arsenic and contribute to the ongoing debate about the threshold-dose of effect, suggesting that even concentrations below 10 μg/L carry a mortality risk. Policy actions are urgently needed in areas exposed to arsenic like in the Viterbo province, to comply with current EU regulations. PMID:26383851

Risk of radiation induced cataracts: investigation of radiation exposure to the eye lens during endourologic procedures.

PubMed

Hartmann, Josefin; Distler, Florian A; Baumueller, Martin; Guni, Ewald; Pahernik, Sascha A; Wucherer, Michael

2018-06-14

Due to new radiobiological data, the ICRP recommends a dose limit of 20mSv per year to the eye lens. Therefore, the IAEA International Basic Safety Standard and the EU council directive 2013/59/EURATOM requires a reduction of the annual dose limit from 150mSv to 20mSv. Urologists are exposed to an elevated radiation exposure in the head region during fluoroscopic interventions, due to the commonly used overtable X-ray tubes and the rarely used radiation protection for the head. Aim of the study was to analyze real radiation exposure to the eye lens of the urologist during various interventions during which the patient is in the lithotomy position. The partial body doses (forehead and apron collar) of the urologists and surgical staff were measured over a period of two months. 95 interventions were performed on Uroskop Omnia Max workplaces (Siemens Healthineers, Erlangen, Germany). Interventions were class-divided in less (stage I) and more complex (stage II) interventions. Two dosimeter-types were applied: well-calibrated electronic personal dosimeter EPD Mk2 and self-calibrated TLD-100H (both Thermo Fisher Scientific, Waltham, USA). The radiation exposure parameters were documented using the dose area product (DAP) and the fluoroscopy time (FT). The correlation between DAP and the apron dose of the urologist was in average 0.07µSv per 1µGym². The more experienced urologists yielded a mean DAP of 166µGym² for stage I and 415µGym² for stage II procedures. The interventionist was exposed with 10µSv in mean outside the lead apron collar. The mean dose value of the eye lenses per intervention was ascertained to 20µSv (mean DAP: 233µGym²). The study setup allows a differentiated and time-resolved measurement of the radiation exposure, which was found heterogeneous depending on intervention and surgeon. In this setting, approximately 1000 interventions can be performed until the annual eye lens dose limit is achieved.

Cannabis with high δ9-THC contents affects perception and visual selective attention acutely: an event-related potential study.

PubMed

Böcker, K B E; Gerritsen, J; Hunault, C C; Kruidenier, M; Mensinga, Tj T; Kenemans, J L

2010-07-01

Cannabis intake has been reported to affect cognitive functions such as selective attention. This study addressed the effects of exposure to cannabis with up to 69.4mg Delta(9)-tetrahydrocannabinol (THC) on Event-Related Potentials (ERPs) recorded during a visual selective attention task. Twenty-four participants smoked cannabis cigarettes with four doses of THC on four test days in a randomized, double blind, placebo-controlled, crossover study. Two hours after THC exposure the participants performed a visual selective attention task and concomitant ERPs were recorded. Accuracy decreased linearly and reaction times increased linearly with THC dose. However, performance measures and most of the ERP components related specifically to selective attention did not show significant dose effects. Only in relatively light cannabis users the Occipital Selection Negativity decreased linearly with dose. Furthermore, ERP components reflecting perceptual processing, as well as the P300 component, decreased in amplitude after THC exposure. Only the former effect showed a linear dose-response relation. The decrements in performance and ERP amplitudes induced by exposure to cannabis with high THC content resulted from a non-selective decrease in attentional or processing resources. Performance requiring attentional resources, such as vehicle control, may be compromised several hours after smoking cannabis cigarettes containing high doses of THC, as presently available in Europe and Northern America. Copyright 2010 Elsevier Inc. All rights reserved.

Mimicking the effects of spaceflight on bone: Combined effects of disuse and chronic low-dose rate radiation exposure on bone mass in mice

NASA Astrophysics Data System (ADS)

Yu, Kanglun; Doherty, Alison H.; Genik, Paula C.; Gookin, Sara E.; Roteliuk, Danielle M.; Wojda, Samantha J.; Jiang, Zhi-Sheng; McGee-Lawrence, Meghan E.; Weil, Michael M.; Donahue, Seth W.

2017-11-01

During spaceflight, crewmembers are subjected to biomechanical and biological challenges including microgravity and radiation. In the skeleton, spaceflight leads to bone loss, increasing the risk of fracture. Studies utilizing hindlimb suspension (HLS) as a ground-based model of spaceflight often neglect the concomitant effects of radiation exposure, and even when radiation is accounted for, it is often delivered at a high-dose rate over a very short period of time, which does not faithfully mimic spaceflight conditions. This study was designed to investigate the skeletal effects of low-dose rate gamma irradiation (8.5 cGy gamma radiation per day for 20 days, amounting to a total dose of 1.7 Gy) when administered simultaneously to disuse from HLS. The goal was to determine whether continuous, low-dose rate radiation administered during disuse would exacerbate bone loss in a murine HLS model. Four groups of 16 week old female C57BL/6 mice were studied: weight bearing + no radiation (WB+NR), HLS + NR, WB + radiation exposure (WB+RAD), and HLS+RAD. Surprisingly, although HLS led to cortical and trabecular bone loss, concurrent radiation exposure did not exacerbate these effects. Our results raise the possibility that mechanical unloading has larger effects on the bone loss that occurs during spaceflight than low-dose rate radiation.

Characterization of glycidol-hemoglobin adducts as biomarkers of exposure and in vivo dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Honda, Hiroshi, E-mail: honda.hiroshi@kao.co.jp; Törnqvist, Margareta; Nishiyama, Naohiro

2014-03-15

Hemoglobin adducts have been used as biomarkers of exposure to reactive chemicals. Glycidol, an animal carcinogen, has been reported to form N-(2,3-dihydroxy-propyl)valine adducts to hemoglobin (diHOPrVal). To support the use of these adducts as markers of glycidol exposure, we investigated the kinetics of diHOPrVal formation and its elimination in vitro and in vivo. Five groups of rats were orally administered a single dose of glycidol ranging from 0 to 75 mg/kg bw, and diHOPrVal levels were measured 24 h after administration. A dose-dependent increase in diHOPrVal levels was observed with high linearity (R{sup 2} = 0.943). Blood sampling at differentmore » time points (1, 10, 20, or 40 days) from four groups administered glycidol at 12 mg/kg bw suggested a linear decrease in diHOPrVal levels compatible with the normal turnover of rat erythrocytes (life span, 61 days), with the calculated first-order elimination rate constant (k{sub el}) indicating that the diHOPrVal adduct was chemically stable. Then, we measured the second-order rate constant (k{sub val}) for the reaction of glycidol with N-terminal valine in rat and human hemoglobin in in vitro experiments with whole blood. The k{sub val} was 6.7 ± 1.1 and 5.6 ± 1.3 (pmol/g globin per μMh) in rat and human blood, respectively, indicating no species differences. In vivo doses estimated from k{sub val} and diHOPrVal levels were in agreement with the area under the (concentration–time) curve values determined in our earlier toxicokinetic study in rats. Our results indicate that diHOPrVal is a useful biomarker for quantification of glycidol exposure and for risk assessment. - Highlight: • Glycidol-hemoglobin adduct (diHOPrVal) was characterized for exposure evaluation. • We studied the kinetics of diHOPrVal formation and elimination in vitro and in vivo. • Dose dependent formation and chemical stability were confirmed in the rat study. • In vivo dose (AUC) of glycidol could be estimated from diHOPrVal levels. • diHOPrVal is considered a useful exposure and in vivo dose marker of G.« less

The use of chlorine dioxide for the inactivation of copepod zooplankton in drinking water treatment.

PubMed

Lin, Tao; Chen, Wei; Cai, Bo

2014-01-01

The presence of zooplankton in drinking water treatment system may cause a negative effect on the aesthetic value of drinking water and may also increase the threat to human health due to they being the carriers of bacteria. Very little research has been done on the effects of copepod inactivation and the mechanisms involved in this process. In a series of bench-scale experiments we used a response surface method to assess the sensitivity of copepod to inactivation when chlorine dioxide (ClO₂) was used as a disinfectant. We also assessed the effects of the ClO₂dosage, exposure time, organic matter concentration and temperature. Results indicated that the inactivation rate improved with increasing dosage, exposure time and temperature, whereas it decreased with increasing organic matter concentration. Copepod inactivation was more sensitive to the ClO₂dose than that to the exposure time, while being maintained at the same Ct-value conditions. The activation energy at different temperatures revealed that the inactivation of copepods with ClO₂was temperature-dependent. The presence of organic matter resulted in a lower available dose as well as a shorter available exposure time, which resulted in a decrease in inactivation efficiency.

Evaluation of entrance surface air kerma in pediatric chest radiography

NASA Astrophysics Data System (ADS)

Porto, L.; Lunelli, N.; Paschuk, S.; Oliveira, A.; Ferreira, J. L.; Schelin, H.; Miguel, C.; Denyak, V.; Kmiecik, C.; Tilly, J.; Khoury, H.

2014-11-01

The objective of this study was to evaluate the entrance surface air kerma in pediatric chest radiography. An evaluation of 301 radiographical examinations in anterior-posterior (AP) and posterior-anterior (PA) (166 examinations) and lateral (LAT) (135 examinations) projections was performed. The analyses were performed on patients grouped by age; the groups included ages 0-1 y, 1-5 y, 5-10 y, and 10-15 y. The entrance surface air kerma was determined with DoseCal software (Radiological Protection Center of Saint George's Hospital, London) and thermoluminescent dosimeters. Two different exposure techniques were compared. The doses received by patients who had undergone LAT examinations were 40% higher, on average, those in AP/PA examinations because of the difference in tube voltage. A large high-dose “tail” was observed for children up to 5 y old. An increase in tube potential and corresponding decrease in current lead to a significant dose reduction. The difference between the average dose values for different age ranges was not practically observed, implying that the exposure techniques are still not optimal. Exposure doses received using the higher tube voltage and lower current-time product correspond to the international diagnostic reference levels.

Gene expression changes in medical workers exposed to radiation.

PubMed

Morandi, Elena; Severini, Cinzia; Quercioli, Daniele; Perdichizzi, Stefania; Mascolo, Maria Grazia; Horn, Wolfango; Vaccari, Monica; Nucci, Maria Concetta; Lodi, Vittorio; Violante, Francesco Saverio; Bolognesi, Claudia; Grilli, Sandro; Silingardi, Paola; Colacci, Annamaria

2009-10-01

The use of nuclear resources for medical purposes causes considerable concern about occupational exposure. Nevertheless, little information is available regarding the effects of low-dose irradiations protracted over time. We used oligomicroarrays to identify the genes that are transcriptionally regulated by persistent exposure to extremely low doses of ionizing radiation in 28 exposed professionals (mean cumulative effective dose +/- SD, 19 +/- 38 mSv) compared with a matched sample of nonexposed subjects. We identified 256 modulated genes from peripheral blood mononuclear cells profiles, and the main biological processes we found were DNA packaging and mitochondrial electron transport NADH to ubiquinone. Next we investigated whether a different pattern existed when only 22 exposed subjects with accumulated doses >2.5 mSv, a threshold corresponding to the natural background radiation in Italy per year, and mean equal to 25 +/- 41 mSv were used. In addition to DNA packaging and NADH dehydrogenase function, the analysis of the higher-exposed subgroup revealed a significant modulation of ion homeostasis and programmed cell death as well. The changes in gene expression that we found suggest different mechanisms from those involved in high-dose studies that may help to define new biomarkers of radiation exposure for accumulated doses below 25 mSv.

Clinical decision-making tools for exam selection, reporting and dose tracking.

PubMed

Brink, James A

2014-10-01

Although many efforts have been made to reduce the radiation dose associated with individual medical imaging examinations to "as low as reasonably achievable," efforts to ensure such examinations are performed only when medically indicated and appropriate are equally if not more important. Variations in the use of ionizing radiation for medical imaging are concerning, regardless of whether they occur on a local, regional or national basis. Such variations among practices can be reduced with the use of decision support tools at the time of order entry. These tools help reduce radiation exposure among practices through the appropriate use of medical imaging. Similarly, adoption of best practices among imaging facilities can be promoted through tracking the radiation exposure among imaging patients. Practices can benchmark their aggregate radiation exposures for medical imaging through the use of dose index registries. However several variables must be considered when contemplating individual patient dose tracking. The specific dose measures and the variation among them introduced by variations in body habitus must be understood. Moreover the uncertainties in risk estimation from dose metrics related to age, gender and life expectancy must also be taken into account.

Exposure-Response Analyses for Tafenoquine after Administration to Patients with Plasmodium vivax Malaria.

PubMed

Tenero, David; Green, Justin A; Goyal, Navin

2015-10-01

Tafenoquine (TQ), a new 8-aminoquinoline with activity against all stages of the Plasmodium vivax life cycle, is being developed for the radical cure of acute P. vivax malaria in combination with chloroquine. The efficacy and exposure data from a pivotal phase 2b dose-ranging study were used to conduct exposure-response analyses for TQ after administration to subjects with P. vivax malaria. TQ exposure (i.e., area under the concentration-time curve [AUC]) and region (Thailand compared to Peru and Brazil) were found to be statistically significant predictors of clinical response based on multivariate logistic regression analyses. After accounting for region/country, the odds of being relapse free at 6 months increased by approximately 51% (95% confidence intervals [CI], 25%, 82%) for each 25-U increase in AUC above the median value of 54.5 μg · h/ml. TQ exposure was also a significant predictor of the time to relapse of the infection. The final parametric, time-to-event model for the time to relapse, included a Weibull distribution hazard function, AUC, and country as covariates. Based on the model, the risk of relapse decreased by 30% (95% CI, 17% to 42%) for every 25-U increase in AUC. Monte Carlo simulations indicated that the 300-mg dose of TQ would provide an AUC greater than the clinically relevant breakpoint obtained in a classification and regression tree (CART) analysis (56.4 μg · h/ml) in more than 90% of subjects and consequently result in a high probability of being relapse free at 6 months. This model-based approach was critical in selecting an appropriate phase 3 dose. (This study has been registered at ClinicalTrials.gov under registration no. NCT01376167.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Exposure-Response Analyses for Tafenoquine after Administration to Patients with Plasmodium vivax Malaria

PubMed Central

Green, Justin A.; Goyal, Navin

2015-01-01

Tafenoquine (TQ), a new 8-aminoquinoline with activity against all stages of the Plasmodium vivax life cycle, is being developed for the radical cure of acute P. vivax malaria in combination with chloroquine. The efficacy and exposure data from a pivotal phase 2b dose-ranging study were used to conduct exposure-response analyses for TQ after administration to subjects with P. vivax malaria. TQ exposure (i.e., area under the concentration-time curve [AUC]) and region (Thailand compared to Peru and Brazil) were found to be statistically significant predictors of clinical response based on multivariate logistic regression analyses. After accounting for region/country, the odds of being relapse free at 6 months increased by approximately 51% (95% confidence intervals [CI], 25%, 82%) for each 25-U increase in AUC above the median value of 54.5 μg · h/ml. TQ exposure was also a significant predictor of the time to relapse of the infection. The final parametric, time-to-event model for the time to relapse, included a Weibull distribution hazard function, AUC, and country as covariates. Based on the model, the risk of relapse decreased by 30% (95% CI, 17% to 42%) for every 25-U increase in AUC. Monte Carlo simulations indicated that the 300-mg dose of TQ would provide an AUC greater than the clinically relevant breakpoint obtained in a classification and regression tree (CART) analysis (56.4 μg · h/ml) in more than 90% of subjects and consequently result in a high probability of being relapse free at 6 months. This model-based approach was critical in selecting an appropriate phase 3 dose. (This study has been registered at ClinicalTrials.gov under registration no. NCT01376167.) PMID:26248362

Model-based dose selection for phase III rivaroxaban study in Japanese patients with non-valvular atrial fibrillation.

PubMed

Tanigawa, Takahiko; Kaneko, Masato; Hashizume, Kensei; Kajikawa, Mariko; Ueda, Hitoshi; Tajiri, Masahiro; Paolini, John F; Mueck, Wolfgang

2013-01-01

The global ROCKET AF phase III trial evaluated rivaroxaban 20 mg once daily (o.d.) for stroke prevention in atrial fibrillation (AF). Based on rivaroxaban pharmacokinetics in Japanese subjects and lower anticoagulation preferences in Japan, particularly in elderly patients, the optimal dose regimen for Japanese AF patients was considered. The aim of this analysis was dose selection for Japanese patients from a pharmacokinetic aspect by comparison of simulated exposure in Japanese patients with those in Caucasian patients. As a result of population pharmacokinetics-pharmacodynamics analyses, a one-compartment pharmacokinetic model with first-order absorption and direct link pharmacokinetic-pharmacodynamic models optimally described the plasma concentration and pharmacodynamic models (Factor Xa activity, prothrombin time, activated partial thromboplastin time, and HepTest), which were also consistent with previous works. Steady-state simulations indicated 15 mg rivaroxaban o.d. doses in Japanese patients with AF would yield exposures comparable to the 20 mg o.d. dose in Caucasian patients with AF. In conclusion, in the context of the lower anticoagulation targets in Japanese practice, the population pharmacokinetic and pharmacodynamic modeling supports 15 mg o.d. as the principal rivaroxaban dose in J-ROCKET AF.

Evaluating strategies for reducing scattered radiation in fixed-imaging hybrid operating suites.

PubMed

Miller, Claire; Kendrick, Daniel; Shevitz, Andrew; Kim, Ann; Baele, Henry; Jordan, David; Kashyap, Vikram S

2018-04-01

High-resolution fixed C-arm fluoroscopic systems allow high-quality endovascular imaging but come at a cost of greater scatter radiation generation and increased occupational exposure for surgeons. The purpose of this study was to evaluate the efficacy of two methods in reducing scattered radiation exposure. There were 164 endovascular cases analyzed in three phases. In phase 1 (P1), baseline radiation exposure was calculated. In phase 2 (P2), staff used real-time radiation dose monitoring (dosimetry badges [RaySafe; Unfors, Hopkinton, Mass]). In phase 3 (P3), a software imaging algorithm was installed that reduced radiation (EcoDose software; Philips Healthcare, Best, The Netherlands). A total of 72 cases in P1, 34 cases in P2, and 58 cases in P3 were analyzed. Total mean dose-area product decreased across each phase, with statistical significance achieved for P1 vs P3 (mean ± standard error of the mean, 186,173 ± 16,754 mGy/cm 2 vs 121,536 ± 11,971 mGy/cm 2 ; P = .002) and P2 vs P3 (171,921 ± 26,276 mGy/cm 2 vs 121,536 ± 11,971 mGy/cm 2 ; P = .04), whereas total mean fluoroscopy time did not significantly differ across any phase. The radiation exposure to the primary operator did not change significantly from P1 to P2 but fell significantly in P3 (0.08 ± 0.02 mSv vs 0.03 ± 0.01 mSv; P = .02). The addition of dose reduction software had the most impact on endovascular aneurysm repair, with reductions in median room dose (P = .03) and primary operator exposure (P2 vs P3; 0.19 ± 0.04 mSv vs 0.03 ± 0.02 mSv; P < .01). Dose reduction software may be an effective technique to lower radiation exposure. Implementation of system-based strategies to reduce radiation is needed to reduce lifetime occupational radiation exposure for endovascular staff and to improve patient safety. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

A review of the cohorts with environmental and occupational mineral fiber exposure.

PubMed

Metintas, Selma; Ak, Guntulu; Metintas, Muzaffer

2018-04-20

The aim of the study was to examine factors associated with Malignant Mesothelioma (MM) incidence rate of the groups with occupational asbestos and environmental asbestos or erionite exposure in rural area. In this ecological study, a total of 21 cohort datasets (8 environmental and 13 occupational) were evaluated. Data were analyzed using a multiple linear regression analysis model. In environmental cohorts, the risk of MM incidence was higher in women and people exposed to erionite. In this cohort, the incidence rate of MM increased as the median exposure time increased, while the incidence decreased as the median cumulative exposure dose increased. In occupational cohorts, the incidence rate of MM was positively correlated with the median cumulative exposure dose. The risk of mesothelioma was lower in those exposed to tremolite than others. Environmental asbestos exposure is as important as occupational exposure to develop MM, and it has its own unique exposure features on the risk of MM.

Repeated exposure to sublethal doses of the organophosphorus compound VX activates BDNF expression in mouse brain.

PubMed

Pizarro, Jose M; Chang, Wenling E; Bah, Mariama J; Wright, Linnzi K M; Saviolakis, George A; Alagappan, Arun; Robison, Christopher L; Shah, Jinesh D; Meyerhoff, James L; Cerasoli, Douglas M; Midboe, Eric G; Lumley, Lucille A

2012-04-01

The highly toxic organophosphorus compound VX [O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonate] is an irreversible inhibitor of the enzyme acetylcholinesterase (AChE). Prolonged inhibition of AChE increases endogenous levels of acetylcholine and is toxic at nerve synapses and neuromuscular junctions. We hypothesized that repeated exposure to sublethal doses of VX would affect genes associated with cell survival, neuronal plasticity, and neuronal remodeling, including brain-derived neurotrophic factor (BDNF). We examined the time course of BDNF expression in C57BL/6 mouse brain following repeated exposure (1/day × 5 days/week × 2 weeks) to sublethal doses of VX (0.2 LD(50) and 0.4 LD(50)). BDNF messenger RNA expression was significantly (p < 0.05) elevated in multiple brain regions, including the dentate gyrus, CA3, and CA1 regions of the hippocampal formation, as well as the piriform cortex, hypothalamus, amygdala, and thalamus, 72 h after the last 0.4 LD(50) VX exposure. BDNF protein expression, however, was only increased in the CA3 region of the hippocampus. Whether increased BDNF in response to sublethal doses of VX exposure is an adaptive response to prevent cellular damage or a precursor to impending brain damage remains to be determined. If elevated BDNF is an adaptive response, exogenous BDNF may be a potential therapeutic target to reduce the toxic effects of nerve agent exposure.

Personalized cumulative UV tracking on mobiles & wearables.

PubMed

Dey, S; Sahoo, S; Agrawal, H; Mondal, A; Bhowmik, T; Tiwari, V N

2017-07-01

Maintaining a balanced Ultra Violet (UV) exposure level is vital for a healthy living as the excess of UV dose can lead to critical diseases such as skin cancer while the absence can cause vitamin D deficiency which has recently been linked to onset of cardiac abnormalities. Here, we propose a personalized cumulative UV dose (CUVD) estimation system for smartwatch and smartphone devices having the following novelty factors; (a) sensor orientation invariant measurement of UV exposure using a bootstrap resampling technique, (b) estimation of UV exposure using only light intensity (lux) sensor (c) optimal UV exposure dose estimation. Our proposed method will eliminate the need for a dedicated UV sensor thus widen the user base of the proposed solution, render it unobtrusive by eliminating the critical requirement of orienting the device in a direction facing the sun. The system is implemented on android mobile platform and validated on 1200 minutes of lux and UV index (UVI) data collected across several days covering morning to evening time frames. The result shows very impressive final UVI estimation accuracy. We believe our proposed solution will enable the future wearable and smartphone users to obtain a seamless personalized UV exposure dose across a day paving a way for simple yet very useful recommendations such as right skin protective measure for reducing risk factors of long term UV exposure related diseases like skin cancer and, cardiac abnormality.

Documenting the kinetic time course of lambda-cyhalothrin metabolites in orally exposed volunteers for the interpretation of biomonitoring data.

PubMed

Khemiri, Rania; Côté, Jonathan; Fetoui, Hamadi; Bouchard, Michèle

2017-07-05

Lambda-cyhalothrin is a pyrethroid pesticide largely used in agriculture. Exposure assessment can be performed by measuring key urinary metabolites. For a proper use of biomonitoring data, it is however important to gain information on the toxicokinetics of these key biomarkers of exposure. A human volunteer study was performed to document the plasma and urinary time courses of major lambda-cyhalothrin metabolites. Seven volunteers ingested 0.025mgkg -1 body weight of lambda-cyhalothrin. Blood samples were withdrawn prior to dosing and at fixed time periods over the 72 h-period following ingestion and complete urine voids were collected pre-exposure and at pre-established intervals over 84h post-dosing. The cis-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (CFMP) and 3-phenoxybenzoic acid (3-PBA) metabolites were quantified in these samples. Plasma concentrations of CFMP and 3-PBA increased rapidly after ingestion, with average peak values at 3.1 and 4.0h post-dosing, respectively; subsequent elimination phase showed a rapid decay with a mean half-life (t ½ ) of ≈5.3 and 6.4h for CFMP and 3-PBA, respectively. Urinary rate time courses displayed a profile similar to the plasma concentration-time curves with corresponding mean t ½ of ≈4.2 and 5.9h. In the 84-h period post-treatment, on average 21% of lambda-cyhalothrin dose were excreted in urine as CFMP as compared to 30% as 3-PBA. Overall, CFMP and 3-PBA metabolites were confirmed to be major metabolites of lambda-cyhalothrin and exhibited similar kinetics with short half-lives; they thus both appear as useful biomarkers of exposure to lambda-cyhalothrin in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

In vitro human epidermal permeation of nicotine from electronic cigarette refill liquids and implications for dermal exposure assessment.

PubMed

Frasch, H Frederick; Barbero, Ana M

2017-11-01

Nicotine plus flavorings in a propylene glycol (PG) vehicle are the components of electronic cigarette liquids (e-liquids), which are vaporized and inhaled by the user. Dermal exposure to nicotine and e-liquids may occur among workers in mixing and filling of e-cigarettes in the manufacturing process. Inadvertent skin contact among consumers is also a concern. In vitro nicotine permeation studies using heat-separated human epidermis were performed with surrogate and two commercial e-liquids, neat and aqueous nicotine donor formulations. Steady-state fluxes (J ss ), and lag times (t lag ) were measured for each formulation. In addition, transient (4 h) exposure and finite dose (1-10 μl/cm 2 ) experiments were undertaken using one commercial e-liquid. Average J ss (μg/cm 2 /h) from formulations were: nicotine in PG (24 mg/ml): 3.97; commercial e-liquid containing menthol (25 mg/ml nicotine): 10.2; commercial e-liquid containing limonene (25 mg/ml nicotine): 23.7; neat nicotine: 175. E-liquid lag times ranged from 5 to 10 h. Absorbed fraction of nicotine from finite doses was ≈0.3 at 48 h. The data were applied to transient exposure and finite dose dermal exposure assessment models and to a simple pharmacokinetic model. Three illustrative exposure scenarios demonstrate use of the data to predict systemic uptake and plasma concentrations from dermal exposure. The data demonstrate the potential for significant nicotine absorption through skin contact with e-cigarette refill solutions and the neat nicotine used to mix them.

Real-time measurement of individual occupational radon exposures in tombs of the Valley of the Kings, Egypt.

PubMed

Gruber, E; Salama, E; Rühm, W

2011-03-01

The active radon exposure meter developed recently at the German Research Center for Environmental Health (Helmholtz Zentrum München) was used to measure radon concentrations in 12 tombs located in the Valley of the Kings, Egypt. Radon concentrations in air between 50 ± 7 and 12 100 ± 600 Bq m(-3) were obtained. The device was also used to measure individual radon exposures of those persons working as safeguards inside the tombs. For a measurement time of 2-3 d, typical individual radon exposures ranged from 1800 ± 400 to 240 000 ± 13 000 Bq h m(-3), depending on the duration of measurement and radon concentration in the different tombs. Based on current ICRP dose conversion conventions for workers and on equilibrium factors published in the literature for these tombs, individual effective dose rates that range from 1.5 ± 0.3 to 860 ± 50 µSv d(-1) were estimated. If it is assumed that the climatic conditions present at the measurement campaign persist for about half a year, in this area, then effective doses up to ∼ 66 mSv could be estimated for half a year, for some of the safeguards of tombs where F-values were known. To reduce the exposure of the safeguards, some recommendations are proposed.

Leaded eyeglasses substantially reduce radiation exposure of the surgeon's eyes during acquisition of typical fluoroscopic views of the hip and pelvis.

PubMed

Burns, Sean; Thornton, Raymond; Dauer, Lawrence T; Quinn, Brian; Miodownik, Daniel; Hak, David J

2013-07-17

Despite recommendations to do so, few orthopaedists wear leaded glasses when performing operative fluoroscopy. Radiation exposure to the ocular lens causes cataracts, and regulatory limits for maximum annual occupational exposure to the eye continue to be revised downward. Using anthropomorphic patient and surgeon phantoms, radiation dose at the surgeon phantom's lens was measured with and without leaded glasses during fluoroscopic acquisition of sixteen common pelvic and hip views. The magnitude of lens dose reduction from leaded glasses was calculated by dividing the unprotected dose by the dose measured behind leaded glasses. On average, the use of leaded glasses reduced radiation to the surgeon phantom's eye by tenfold, a 90% reduction in dose. However, there was widespread variation in the amount of radiation that reached the phantom surgeon's eye among the various radiographic projections we studied. Without leaded glasses, the dose measured at the surgeon's lens varied more than 250-fold among these sixteen different views. In addition to protecting the surgeon's eye from the deleterious effects of radiation, the use of leaded glasses could permit an orthopaedist to perform fluoroscopic views on up to ten times more patients before reaching the annual dose limit of 20 mSv of radiation to the eye recommended by the International Commission on Radiological Protection. Personal safety and adherence to limits of occupational radiation exposure should compel orthopaedists to wear leaded glasses for fluoroscopic procedures if other protective barriers are not in use. Leaded glasses are a powerful tool for reducing the orthopaedic surgeon's lens exposure to radiation during acquisition of common intraoperative fluoroscopic views.

Assessment of serum biomarkers in rats after exposure to pesticides of different chemical classes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moser, Virginia C., E-mail: Moser.ginger@epa.gov; Stewart, Nicholas; Freeborn, Danielle L.

There is increasing emphasis on the use of biomarkers of adverse outcomes in safety assessment and translational research. We evaluated serum biomarkers and targeted metabolite profiles after exposure to pesticides (permethrin, deltamethrin, imidacloprid, carbaryl, triadimefon, fipronil) with different neurotoxic actions. Adult male Long–Evans rats were evaluated after single exposure to vehicle or one of two doses of each pesticide at the time of peak effect. The doses were selected to produce similar magnitude of behavioral effects across chemicals. Serum or plasma was analyzed using commercial cytokine/protein panels and targeted metabolomics. Additional studies of fipronil used lower doses (lacking behavioral effects),more » singly or for 14 days, and included additional markers of exposure and biological activity. Biomarker profiles varied in the number of altered analytes and patterns of change across pesticide classes, and discriminant analysis could separate treatment groups from control. Low doses of fipronil produced greater effects when given for 14 days compared to a single dose. Changes in thyroid hormones and relative amounts of fipronil and its sulfone metabolite also differed between the dosing regimens. Most cytokine changes reflected alterations in inflammatory responses, hormone levels, and products of phospholipid, fatty acid, and amino acid metabolism. These findings demonstrate distinct blood-based analyte profiles across pesticide classes, dose levels, and exposure duration. These results show promise for detailed analyses of these biomarkers and their linkages to biological pathways. - Highlights: • Pesticides typical of different classes produced distinct patterns of change in biomarker panels. • Based on the panels used, alterations suggest impacts on immune, metabolism, and homeostasis functions. • Some changes may reflect actions on neurotransmitter systems involved in immune modulation. • Fipronil effects on thyroid and kinetics differed with acute and repeated administration.« less

Accounting for patient size in the optimization of dose and image quality of pelvis cone beam CT protocols on the Varian OBI system

PubMed Central

Moore, Craig S; Horsfield, Carl J; Saunderson, John R; Beavis, Andrew W

2015-01-01

Objective: The purpose of this study was to develop size-based radiotherapy kilovoltage cone beam CT (CBCT) protocols for the pelvis. Methods: Image noise was measured in an elliptical phantom of varying size for a range of exposure factors. Based on a previously defined “small pelvis” reference patient and CBCT protocol, appropriate exposure factors for small, medium, large and extra-large patients were derived which approximate the image noise behaviour observed on a Philips CT scanner (Philips Medical Systems, Best, Netherlands) with automatic exposure control (AEC). Selection criteria, based on maximum tube current–time product per rotation selected during the radiotherapy treatment planning scan, were derived based on an audit of patient size. Results: It has been demonstrated that 110 kVp yields acceptable image noise for reduced patient dose in pelvic CBCT scans of small, medium and large patients, when compared with manufacturer's default settings (125 kVp). Conversely, extra-large patients require increased exposure factors to give acceptable images. 57% of patients in the local population now receive much lower radiation doses, whereas 13% require higher doses (but now yield acceptable images). Conclusion: The implementation of size-based exposure protocols has significantly reduced radiation dose to the majority of patients with no negative impact on image quality. Increased doses are required on the largest patients to give adequate image quality. Advances in knowledge: The development of size-based CBCT protocols that use the planning CT scan (with AEC) to determine which protocol is appropriate ensures adequate image quality whilst minimizing patient radiation dose. PMID:26419892

Population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children with tuberculosis: in silico evaluation of currently recommended doses

PubMed Central

Zvada, Simbarashe P.; Denti, Paolo; Donald, Peter R.; Schaaf, H. Simon; Thee, Stephanie; Seddon, James A.; Seifart, Heiner I.; Smith, Peter J.; McIlleron, Helen M.; Simonsson, Ulrika S. H.

2014-01-01

Objectives To describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children and evaluate the adequacy of steady-state exposures. Patients and methods We used previously published data for 76 South African children with tuberculosis to describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid. Monte Carlo simulations were used to predict steady-state exposures in children following doses in fixed-dose combination tablets in accordance with the revised guidelines. Reference exposures were derived from an ethnically similar adult population with tuberculosis taking currently recommended doses. Results The final models included allometric scaling of clearance and volume of distribution using body weight. Maturation was included for clearance of isoniazid and clearance and absorption transit time of rifampicin. For a 2-year-old child weighing 12.5 kg, the estimated typical oral clearances of rifampicin and pyrazinamide were 8.15 and 1.08 L/h, respectively. Isoniazid typical oral clearance (adjusted for bioavailability) was predicted to be 4.44, 11.6 and 14.6 L/h for slow, intermediate and fast acetylators, respectively. Higher oral clearance values in intermediate and fast acetylators also resulted from 23% lower bioavailability compared with slow acetylators. Conclusions Simulations based on our models suggest that with the new WHO dosing guidelines and utilizing available paediatric fixed-dose combinations, children will receive adequate rifampicin exposures when compared with adults, but with a larger degree of variability. However, pyrazinamide and isoniazid exposures in many children will be lower than in adults. Further studies are needed to confirm these findings in children administered the revised dosages and to optimize pragmatic approaches to dosing. PMID:24486870

Exposure time independent summary statistics for assessment of drug dependent cell line growth inhibition.

PubMed

Falgreen, Steffen; Laursen, Maria Bach; Bødker, Julie Støve; Kjeldsen, Malene Krag; Schmitz, Alexander; Nyegaard, Mette; Johnsen, Hans Erik; Dybkær, Karen; Bøgsted, Martin

2014-06-05

In vitro generated dose-response curves of human cancer cell lines are widely used to develop new therapeutics. The curves are summarised by simplified statistics that ignore the conventionally used dose-response curves' dependency on drug exposure time and growth kinetics. This may lead to suboptimal exploitation of data and biased conclusions on the potential of the drug in question. Therefore we set out to improve the dose-response assessments by eliminating the impact of time dependency. First, a mathematical model for drug induced cell growth inhibition was formulated and used to derive novel dose-response curves and improved summary statistics that are independent of time under the proposed model. Next, a statistical analysis workflow for estimating the improved statistics was suggested consisting of 1) nonlinear regression models for estimation of cell counts and doubling times, 2) isotonic regression for modelling the suggested dose-response curves, and 3) resampling based method for assessing variation of the novel summary statistics. We document that conventionally used summary statistics for dose-response experiments depend on time so that fast growing cell lines compared to slowly growing ones are considered overly sensitive. The adequacy of the mathematical model is tested for doxorubicin and found to fit real data to an acceptable degree. Dose-response data from the NCI60 drug screen were used to illustrate the time dependency and demonstrate an adjustment correcting for it. The applicability of the workflow was illustrated by simulation and application on a doxorubicin growth inhibition screen. The simulations show that under the proposed mathematical model the suggested statistical workflow results in unbiased estimates of the time independent summary statistics. Variance estimates of the novel summary statistics are used to conclude that the doxorubicin screen covers a significant diverse range of responses ensuring it is useful for biological interpretations. Time independent summary statistics may aid the understanding of drugs' action mechanism on tumour cells and potentially renew previous drug sensitivity evaluation studies.

Exposure time independent summary statistics for assessment of drug dependent cell line growth inhibition

PubMed Central

2014-01-01

Background In vitro generated dose-response curves of human cancer cell lines are widely used to develop new therapeutics. The curves are summarised by simplified statistics that ignore the conventionally used dose-response curves’ dependency on drug exposure time and growth kinetics. This may lead to suboptimal exploitation of data and biased conclusions on the potential of the drug in question. Therefore we set out to improve the dose-response assessments by eliminating the impact of time dependency. Results First, a mathematical model for drug induced cell growth inhibition was formulated and used to derive novel dose-response curves and improved summary statistics that are independent of time under the proposed model. Next, a statistical analysis workflow for estimating the improved statistics was suggested consisting of 1) nonlinear regression models for estimation of cell counts and doubling times, 2) isotonic regression for modelling the suggested dose-response curves, and 3) resampling based method for assessing variation of the novel summary statistics. We document that conventionally used summary statistics for dose-response experiments depend on time so that fast growing cell lines compared to slowly growing ones are considered overly sensitive. The adequacy of the mathematical model is tested for doxorubicin and found to fit real data to an acceptable degree. Dose-response data from the NCI60 drug screen were used to illustrate the time dependency and demonstrate an adjustment correcting for it. The applicability of the workflow was illustrated by simulation and application on a doxorubicin growth inhibition screen. The simulations show that under the proposed mathematical model the suggested statistical workflow results in unbiased estimates of the time independent summary statistics. Variance estimates of the novel summary statistics are used to conclude that the doxorubicin screen covers a significant diverse range of responses ensuring it is useful for biological interpretations. Conclusion Time independent summary statistics may aid the understanding of drugs’ action mechanism on tumour cells and potentially renew previous drug sensitivity evaluation studies. PMID:24902483

Organ S values and effective doses for family members exposed to adult patients following I-131 treatment: A Monte Carlo simulation study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Eun Young; Lee, Choonsik; Mcguire, Lynn

Purpose: To calculate organ S values (mGy/Bq-s) and effective doses per time-integrated activity (mSv/Bq-s) for pediatric and adult family members exposed to an adult male or female patient treated with I-131 using a series of hybrid computational phantoms coupled with a Monte Carlo radiation transport technique.Methods: A series of pediatric and adult hybrid computational phantoms were employed in the study. Three different exposure scenarios were considered: (1) standing face-to-face exposures between an adult patient and pediatric or adult family phantoms at five different separation distances; (2) an adult female patient holding her newborn child, and (3) a 1-yr-old child standingmore » on the lap of an adult female patient. For the adult patient model, two different thyroid-related diseases were considered: hyperthyroidism and differentiated thyroid cancer (DTC) with corresponding internal distributions of {sup 131}I. A general purpose Monte Carlo code, MCNPX v2.7, was used to perform the Monte Carlo radiation transport.Results: The S values show a strong dependency on age and organ location within the family phantoms at short distances. The S values and effective dose per time-integrated activity from the adult female patient phantom are relatively high at shorter distances and to younger family phantoms. At a distance of 1 m, effective doses per time-integrated activity are lower than those values based on the NRC (Nuclear Regulatory Commission) by a factor of 2 for both adult male and female patient phantoms. The S values to target organs from the hyperthyroid-patient source distribution strongly depend on the height of the exposed family phantom, so that their values rapidly decrease with decreasing height of the family phantom. Active marrow of the 10-yr-old phantom shows the highest S values among family phantoms for the DTC-patient source distribution. In the exposure scenario of mother and baby, S values and effective doses per time-integrated activity to the newborn and 1-yr-old phantoms for a hyperthyroid-patient source are higher than values for a DTC-patient source.Conclusions: The authors performed realistic assessments of {sup 131}I organ S values and effective dose per time-integrated activity from adult patients treated for hyperthyroidism and DTC to family members. In addition, the authors’ studies consider Monte Carlo simulated “mother and baby/child” exposure scenarios for the first time. Based on these results, the authors reconfirm the strong conservatism underlying the point source method recommended by the US NRC. The authors recommend that various factors such as the type of the patient's disease, the age of family members, and the distance/posture between the patient and family members must be carefully considered to provide realistic dose estimates for patient-to-family exposures.« less

Fluconazole Pharmacokinetics in Galleria mellonella Larvae and Performance Evaluation of a Bioassay Compared to Liquid Chromatography-Tandem Mass Spectrometry for Hemolymph Specimens

PubMed Central

Astvad, Karen Marie Thyssen; Meletiadis, Joseph; Whalley, Sarah

2017-01-01

ABSTRACT The invertebrate model organism Galleria mellonella can be used to assess the efficacy of treatment of fungal infection. The fluconazole dose best mimicking human exposure during licensed dosing is unknown. We validated a bioassay for fluconazole detection in hemolymph and determined the fluconazole pharmacokinetics and pharmacodynamics in larval hemolymph in order to estimate a humanized dose for future experiments. A bioassay using 4-mm agar wells, 20 μl hemolymph, and the hypersusceptible Candida albicans DSY2621 was established and compared to a validated liquid chromatography-tandem mass spectrometry (LC–MS-MS) method. G. mellonella larvae were injected with fluconazole (5, 10, and 20 mg/kg of larval weight), and hemolymph was harvested for 24 h for pharmacokinetics calculations. The exposure was compared to the human exposure during standard licensed dosing. The bioassay had a linear standard curve between 1 and 20 mg/liter. Accuracy and coefficients of variation (percent) values were below 10%. The Spearman coefficient between assays was 0.94. Fluconazole larval pharmacokinetics followed one-compartment linear kinetics, with the 24-h area under the hemolymph concentration-time curve (AUC24 h) being 93, 173, and 406 mg · h/liter for the three doses compared to 400 mg · h/liter in humans under licensed treatment. In conclusion, a bioassay was validated for fluconazole determination in hemolymph. The pharmacokinetics was linear. An exposure comparable to the human exposure during standard licensed dosing was obtained with 20 mg/kg. PMID:28760893

Near infrared radiation damage mechanism in the lens

NASA Astrophysics Data System (ADS)

Söderberg, Per G.; Talebizadeh, Nooshin; Galichanin, Konstantin; Kronschläger, Martin; Schulmeister, Karl; Yu, Zhaohua

2015-03-01

The current data strongly indicates that there is no photochemical effect of in vivo exposure to 1090 nm near IRR radiation within the pupil. Four groups of 20 Sprague-Dawley rats were unilaterally exposed in vivo to 96 W·cm-2 centered inside the pupil for 10, 18, 33 and 60 min, respectively depending on group belonging. This resulted in radiant exposure doses of 57, 103, 198 and 344 kJ·cm-2. Temperature evolution at the limbus during the exposure and difference of intensity of forward light scattering between the exposed and the contralateral not exposed eye was measured at 1 week after exposure. The temperature at the limbus was found to increase exponentially towards an asymptote with an asymptote temperature of around 7 °C and a time constant (1/k) of around 15 s. No increase of light scattering was found despite that the cumulated radiant exposure dose was [80;250] times the threshold for photochemically induced cataract suggested by previous empirical data. It is concluded that at 1090 nm near IRR there is no photochemical effect.

The injury and cumulative effects on human skin by UV exposure from artificial fluorescence emission.

PubMed

Tian, Yan; Liu, Wei; Niu, TianHui; Dai, CaiHong; Li, Xiaoxin; Cui, Caijuan; Zhao, Xinyan; E, Yaping; Lu, Hui

2014-01-01

The injury and cumulative effects of UV emission from fluorescence lamp were studied. UV intensity from fluorescence lamp was measured, and human skin samples (hips, 10 volunteers) were exposed to low-dose UV irradiation (three times per week for 13 consecutive weeks). Three groups were examined: control group without UV radiation; low-dose group with a cumulative dose of 50 J cm(-2) which was equivalent to irradiation of the face during indoor work for 1.5 years; and high-dose group with 1000 J cm(-2) cumulative dose equivalent to irradiation of the face during outdoor activities for 1 year. Specific indicators were measured before and after UVA irradiation. The findings showed that extending the low-dose UVA exposure decreased the skin moisture content and increased the transepidermal water loss as well as induced skin color changes (decreased L* value, increased M index). Furthermore, irradiated skin showed an increased thickness of cuticle and epidermis, skin edema, light color and unclear staining collagen fibers in the dermis, and elastic fiber fragmentation. In addition, MMP-1, p53 and SIRT1 expression was also increased. Long-term exposure of low-dose UVA radiation enhanced skin photoaging. The safety of the fluorescent lamp needs our attention. © 2014 The American Society of Photobiology.

The effects of two different doses of ultraviolet-A light exposure on nitric oxide metabolites and cardiorespiratory outcomes.

PubMed

Monaghan, Chris; McIlvenna, Luke C; Liddle, Luke; Burleigh, Mia; Weller, Richard B; Fernandez, Bernadette O; Feelisch, Martin; Muggeridge, David J; Easton, Chris

2018-05-01

The present study investigated different doses of ultraviolet-A (UV-A) light on plasma nitric oxide metabolites and cardiorespiratory variables. Ten healthy male participants completed three experimental conditions, 7 days apart. Participants were exposed to no light (CON); 10 J cm 2 (15 min) of UV-A light (UVA10) and 20 J cm 2 (30 min) of UV-A light (UVA20) in a randomized order. Plasma nitrite [NO 2 - ] and nitrate [NO 3 - ] concentrations, blood pressure (BP), and heart rate (HR) were recorded before, immediately after exposure and 30 min post-exposure. Whole body oxygen utilization ([Formula: see text]), resting metabolic rate (RMR) and skin temperature were recorded continuously. None of the measured parameters changed significantly during CON (all P > 0.05). [Formula: see text] and RMR were significantly reduced immediately after UVA10 (P < 0.05) despite no change in plasma [NO 2 - ] (P > 0.05). Immediately after exposure to UVA20, plasma [NO 2 - ] was higher (P = 0.014) and [Formula: see text] and RMR tended to be lower compared to baseline (P = 0.06). There were no differences in [NO 2 - ] or [Formula: see text] at the 30 min time point in any condition. UV-A exposure did not alter systolic BP, diastolic BP or MAP (all P > 0.05). UV-A light did not alter plasma [NO 3 - ] at any time point (all P > 0.05). This study demonstrates that a UV-A dose of 20 J cm 2 is necessary to increase plasma [NO 2 - ] although a smaller dose is capable of reducing [Formula: see text] and RMR at rest. Exposure to UV-A did not significantly reduce BP in this cohort of healthy adults. These data suggest that exposure to sunlight has a meaningful acute impact on metabolic function.

Micronucleus formation induced by dielectric barrier discharge plasma exposure in brain cancer cells

NASA Astrophysics Data System (ADS)

Kaushik, Nagendra K.; Uhm, Hansup; Ha Choi, Eun

2012-02-01

Induction of micronucleus formation (cytogenetic damage) in brain cancer cells upon exposure of dielectric barrier discharge plasma has been investigated. We have investigated the influence of exposure and incubation times on T98G brain cancer cells by using growth kinetic, clonogenic, and micronucleus formation assay. We found that micronucleus formation rate directly depends on the plasma exposure time. It is also shown that colony formation capacity of cells has been inhibited by the treatment of plasma at all doses. Cell death and micronucleus formation are shown to be significantly elevated by 120 and 240 s exposure of dielectric barrier discharge plasma.

ESTIMATION OF UV-B EXPOSURE IN AMPHIBIAN AQUATIC ENVIRONMENTS

EPA Science Inventory

Estimation of ultraviolet radiation B (UV-B; 280 to 320 nm wavelenghts) dose is essential for determining whether UV-B contributes to amphibian population declines and malformations. UV-B dose in wetlands is effected by location, time of day and year, atmospheric levels of ozone,...

A Reanalysis of Curvature in the Dose Response for Cancer and Modifications by Age at Exposure Following Radiation Therapy for Benign Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Little, Mark P., E-mail: mark.little@nih.gov; Stovall, Marilyn; Smith, Susan A.

Purpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy{sup -1} of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018,more » 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. Conclusions: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.« less

γ-H2AX Kinetic Profile in Mouse Lymphocytes Exposed to the Internal Emitters Cesium-137 and Strontium-90

PubMed Central

Turner, Helen C.; Shuryak, Igor; Weber, Waylon; Doyle-Eisele, Melanie; Melo, Dunstana; Guilmette, Raymond; Amundson, Sally A.; Brenner, David J.

2015-01-01

In the event of a dirty bomb scenario or an industrial nuclear accident, a significant dose of volatile radionuclides such as 137Cs and 90Sr may be dispersed into the atmosphere as a component of fallout and inhaled or ingested by hundreds and thousands of people. To study the effects of prolonged exposure to ingested radionuclides, we have performed long-term (30 day) internal-emitter mouse irradiations using soluble-injected 137CsCl and 90SrCl2 radioisotopes. The effect of ionizing radiation on the induction and repair of DNA double strand breaks (DSBs) in peripheral mouse lymphocytes in vivo was determined using the γ-H2AX biodosimetry marker. Using a serial sacrifice experimental design, whole-body radiation absorbed doses for 137Cs (0 to 10 Gy) and 90Sr (0 to 49 Gy) were delivered over 30 days following exposure to each radionuclide. The committed absorbed doses of the two internal emitters as a function of time post exposure were calculated based on their retention parameters and their derived dose coefficients for each specific sacrifice time. In order to measure the kinetic profile for γ-H2AX, peripheral blood samples were drawn at 5 specific timed dose points over the 30-day study period and the total γ-H2AX nuclear fluorescence per lymphocyte was determined using image analysis software. A key finding was that a significant γ-H2AX signal was observed in vivo several weeks after a single radionuclide exposure. A mechanistically-motivated model was used to analyze the temporal kinetics of γ-H2AX fluorescence. Exposure to either radionuclide showed two peaks of γ-H2AX: one within the first week, which may represent the death of mature, differentiated lymphocytes, and the second at approximately three weeks, which may represent the production of new lymphocytes from damaged progenitor cells. The complexity of the observed responses to internal irradiation is likely caused by the interplay between continual production and repair of DNA damage, cell cycle effects and apoptosis. PMID:26618801

γ-H2AX Kinetic Profile in Mouse Lymphocytes Exposed to the Internal Emitters Cesium-137 and Strontium-90.

PubMed

Turner, Helen C; Shuryak, Igor; Weber, Waylon; Doyle-Eisele, Melanie; Melo, Dunstana; Guilmette, Raymond; Amundson, Sally A; Brenner, David J

2015-01-01

In the event of a dirty bomb scenario or an industrial nuclear accident, a significant dose of volatile radionuclides such as 137Cs and 90Sr may be dispersed into the atmosphere as a component of fallout and inhaled or ingested by hundreds and thousands of people. To study the effects of prolonged exposure to ingested radionuclides, we have performed long-term (30 day) internal-emitter mouse irradiations using soluble-injected 137CsCl and 90SrCl2 radioisotopes. The effect of ionizing radiation on the induction and repair of DNA double strand breaks (DSBs) in peripheral mouse lymphocytes in vivo was determined using the γ-H2AX biodosimetry marker. Using a serial sacrifice experimental design, whole-body radiation absorbed doses for 137Cs (0 to 10 Gy) and 90Sr (0 to 49 Gy) were delivered over 30 days following exposure to each radionuclide. The committed absorbed doses of the two internal emitters as a function of time post exposure were calculated based on their retention parameters and their derived dose coefficients for each specific sacrifice time. In order to measure the kinetic profile for γ-H2AX, peripheral blood samples were drawn at 5 specific timed dose points over the 30-day study period and the total γ-H2AX nuclear fluorescence per lymphocyte was determined using image analysis software. A key finding was that a significant γ-H2AX signal was observed in vivo several weeks after a single radionuclide exposure. A mechanistically-motivated model was used to analyze the temporal kinetics of γ-H2AX fluorescence. Exposure to either radionuclide showed two peaks of γ-H2AX: one within the first week, which may represent the death of mature, differentiated lymphocytes, and the second at approximately three weeks, which may represent the production of new lymphocytes from damaged progenitor cells. The complexity of the observed responses to internal irradiation is likely caused by the interplay between continual production and repair of DNA damage, cell cycle effects and apoptosis.

Dose-response characteristics of an amorphous silicon EPID.

PubMed

Winkler, Peter; Hefner, Alfred; Georg, Dietmar

2005-10-01

Electronic portal imaging devices (EPIDs) were originally developed for the purpose of patient setup verification. Nowadays, they are increasingly used as dosimeters (e.g., for IMRT verification and linac-specific QA). A prerequisite for any clinical dosimetric application is a detailed understanding of the detector's dose-response behavior. The aim of this study is to investigate the dosimetric properties of an amorphous silicon EPID (Elekta IVIEWGT) with respect to three photon beam qualities: 6, 10, and 25 MV. The EPID showed an excellent temporal stability on short term as well as on long term scales. The stability throughout the day was strongly influenced by warming up, which took several hours and affected EPID response by 2.5%. Ghosting effects increased the sensitivity of the EPID. They became more pronounced with decreasing time intervals between two exposures as well as with increasing dose. Due to ghosting, changes in pixel sensitivity amounted up to 16% (locally) for the 25 MV photon beam. It was observed that the response characteristics of our EPID depended on dose as well as on dose rate. Doubling the dose rate increased the EPID sensitivity by 1.5%. This behavior was successfully attributed to a dose per frame effect, i.e., a nonlinear relationship between the EPID signal and the dose which was delivered to the panel between two successive readouts. The sensitivity was found to vary up to 10% in the range of 1 to 1000 monitor units. This variation was governed by two independent effects. For low doses, the EPID signal was reduced due to the linac's changing dose rate during startup. Furthermore, the detector reading was influenced by intrabeam variations of EPID sensitivity, namely, an increase of detector response during uniform exposure. For the beam qualities which were used, the response characteristics of the EPID did not depend on energy. Differences in relative dose-response curves resulted from energy dependent temporal output characteristics of the accelerator. If ghosting is prevented from affecting the results and all dose-response effects are properly corrected for, the EPID signal becomes independent of dose rate, dose, and exposure time.

Absolute dose calibration of an X-ray system and dead time investigations of photon-counting techniques

NASA Astrophysics Data System (ADS)

Carpentieri, C.; Schwarz, C.; Ludwig, J.; Ashfaq, A.; Fiederle, M.

2002-07-01

High precision concerning the dose calibration of X-ray sources is required when counting and integrating methods are compared. The dose calibration for a dental X-ray tube was executed with special dose calibration equipment (dosimeter) as function of exposure time and rate. Results were compared with a benchmark spectrum and agree within ±1.5%. Dead time investigations with the Medipix1 photon-counting chip (PCC) have been performed by rate variations. Two different types of dead time, paralysable and non-paralysable will be discussed. The dead time depends on settings of the front-end electronics and is a function of signal height, which might lead to systematic defects of systems. Dead time losses in excess of 30% have been found for the PCC at 200 kHz absorbed photons per pixel.

Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Sea-Air-Land.

PubMed

Lieberman, Harris R; Tharion, William J; Shukitt-Hale, Barbara; Speckman, Karen L; Tulley, Richard

2002-11-01

When humans are acutely exposed to multiple stressors, cognitive performance is substantially degraded. Few practical strategies are available to sustain performance under such conditions. This study examined whether moderate doses of caffeine would reduce adverse effects of sleep deprivation and exposure to severe environmental and operational stress on cognitive performance. Volunteers were 68 U.S. Navy Sea-Air-Land (SEAL) trainees, randomly assigned to receive either 100, 200, or 300 mg caffeine or placebo in capsule form after 72 h of sleep deprivation and continuous exposure to other stressors. Cognitive tests administered included scanning visual vigilance, four-choice visual reaction time, a matching-to-sample working memory task and a repeated acquisition test of motor learning and memory. Mood state, marksmanship, and saliva caffeine were also assessed. Testing was conducted 1 and 8 h after treatment. Sleep deprivation and environmental stress adversely affected performance and mood. Caffeine, in a dose-dependent manner, mitigated many adverse effects of exposure to multiple stressors. Caffeine (200 and 300 mg) significantly improved visual vigilance, choice reaction time, repeated acquisition, self-reported fatigue and sleepiness with the greatest effects on tests of vigilance, reaction time, and alertness. Marksmanship, a task that requires fine motor coordination and steadiness, was not affected by caffeine. The greatest effects of caffeine were present 1 h post-administration, but significant effects persisted for 8 h. Even in the most adverse circumstances, moderate doses of caffeine can improve cognitive function, including vigilance, learning, memory, and mood state. When cognitive performance is critical and must be maintained during exposure to severe stress, administration of caffeine may provide a significant advantage. A dose of 200 mg appears to be optimal under such conditions.

Emergency Dose Estimation Using Optically Stimulated Luminescence from Human Tooth Enamel.

PubMed

Sholom, S; Dewitt, R; Simon, S L; Bouville, A; McKeever, S W S

2011-09-01

Human teeth were studied for potential use as emergency Optically Stimulated Luminescence (OSL) dosimeters. By using multiple-teeth samples in combination with a custom-built sensitive OSL reader, (60)Co-equivalent doses below 0.64 Gy were measured immediately after exposure with the lowest value being 27 mGy for the most sensitive sample. The variability of OSL sensitivity, from individual to individual using multiple-teeth samples, was determined to be 53%. X-ray and beta exposure were found to produce OSL curves with the same shape that differed from those due to ultraviolet (UV) exposure; as a result, correlation was observed between OSL signals after X-ray and beta exposure and was absent if compared to OSL signals after UV exposure. Fading of the OSL signal was "typical" for most teeth with just a few of incisors showing atypical behavior. Typical fading dependences were described by a bi-exponential decay function with "fast" (decay time around of 12 min) and "slow" (decay time about 14 h) components. OSL detection limits, based on the techniques developed to-date, were found to be satisfactory from the point-of-view of medical triage requirements if conducted within 24 hours of the exposure.

Low dose radiation risks for women surviving the a-bombs in Japan: generalized additive model.

PubMed

Dropkin, Greg

2016-11-24

Analyses of cancer mortality and incidence in Japanese A-bomb survivors have been used to estimate radiation risks, which are generally higher for women. Relative Risk (RR) is usually modelled as a linear function of dose. Extrapolation from data including high doses predicts small risks at low doses. Generalized Additive Models (GAMs) are flexible methods for modelling non-linear behaviour. GAMs are applied to cancer incidence in female low dose subcohorts, using anonymous public data for the 1958 - 1998 Life Span Study, to test for linearity, explore interactions, adjust for the skewed dose distribution, examine significance below 100 mGy, and estimate risks at 10 mGy. For all solid cancer incidence, RR estimated from 0 - 100 mGy and 0 - 20 mGy subcohorts is significantly raised. The response tapers above 150 mGy. At low doses, RR increases with age-at-exposure and decreases with time-since-exposure, the preferred covariate. Using the empirical cumulative distribution of dose improves model fit, and capacity to detect non-linear responses. RR is elevated over wide ranges of covariate values. Results are stable under simulation, or when removing exceptional data cells, or adjusting neutron RBE. Estimates of Excess RR at 10 mGy using the cumulative dose distribution are 10 - 45 times higher than extrapolations from a linear model fitted to the full cohort. Below 100 mGy, quasipoisson models find significant effects for all solid, squamous, uterus, corpus, and thyroid cancers, and for respiratory cancers when age-at-exposure > 35 yrs. Results for the thyroid are compatible with studies of children treated for tinea capitis, and Chernobyl survivors. Results for the uterus are compatible with studies of UK nuclear workers and the Techa River cohort. Non-linear models find large, significant cancer risks for Japanese women exposed to low dose radiation from the atomic bombings. The risks should be reflected in protection standards.

Factors that elevate the internal radionuclide and chemical retention, dose and health risks to infants and children in a radiological-nuclear emergency.

PubMed

Richardson, Richard B

2009-06-01

The factors that influence the dose and risk to vulnerable population groups from exposure and internal uptake of chemicals are examined and, in particular, the radionuclides released in chemical, biological, radiological, nuclear and explosive events. The paper seeks to identify the areas that would benefit from further research. The intake and body burdens of carbon and calcium were assessed as surrogates for contaminants that either act like or bind to hydrocarbons (e.g. tritium and (14)C) or bone-seeking radionuclides (e.g. (90)Sr and (239)Pu). The shortest turnover times for such materials in the whole body were evaluated for the newborn: 11 d and 0.5 y for carbon and calcium, respectively. However, their biokinetic behaviour is complicated by a particularly high percentage of the gut-absorbed dietary intake of carbon (approximately 16%) and calcium (approximately 100%) that is incorporated into the soft tissue and skeleton of the growing neonate. The International Commission on Radiological Protection dose coefficients (Sv Bq(-1)) were examined for 14 radionuclides, including 9 of concern because of their potential use in radiological dispersal devices. The dose coefficients for a 3-month-old are greater than those for adults (2-56 times more for ingestion and 2-12 times for inhalation). The age-dependent dose and exposure assessment of contaminant intakes would improve by accounting for gender and growth where it is currently neglected. Health risk is evaluated as the product of the exposure and hazard factors, the latter being about 10-fold greater in infants than in adults. The exposure factor is also approximately 10-fold higher for ingestion by infants than by adults, and unity for inhalation varying with the contaminant. Qualitative and quantitative physiological and epidemiological evidence supports infants being more vulnerable to cancer and neurological deficit than older children.

EPA's SHEDS-multimedia model: children's cumulative pyrethroid exposure estimates and evaluation against NHANES biomarker data.

PubMed

Xue, Jianping; Zartarian, Valerie; Tornero-Velez, Rogelio; Tulve, Nicolle S

2014-12-01

The U.S. EPA's SHEDS-Multimedia model was applied to enhance the understanding of children's exposures and doses to multiple pyrethroid pesticides, including major contributing chemicals and pathways. This paper presents combined dietary and residential exposure estimates and cumulative doses for seven commonly used pyrethroids, and comparisons of model evaluation results with NHANES biomarker data for 3-PBA and DCCA metabolites. Model input distributions were fit to publicly available pesticide usage survey data, NHANES, and other studies, then SHEDS-Multimedia was applied to estimate total pyrethroid exposures and doses for 3-5 year olds for one year variability simulations. For dose estimations we used a pharmacokinetic model and two approaches for simulating dermal absorption. SHEDS-Multimedia predictions compared well to NHANES biomarker data: ratios of 3-PBA observed data to SHEDS-Multimedia modeled results were 0.88, 0.51, 0.54 and 1.02 for mean, median, 95th, and 99th percentiles, respectively; for DCCA, the ratios were 0.82, 0.53, 0.56, and 0.94. Modeled time-averaged cumulative absorbed dose of the seven pyrethroids was 3.1 nmol/day (versus 8.4 nmol/day for adults) in the general population (residential pyrethroid use and non-use homes) and 6.7 nmol/day (versus 10.5 nmol/day for adults) in the simulated residential pyrethroid use population. For the general population, contributions to modeled cumulative dose by chemical were permethrin (60%), cypermethrin (22%), and cyfluthrin (16%); for residential use homes, contributions were cypermethrin (49%), permethrin (29%), and cyfluthrin (17%). The primary exposure route for 3-5 year olds in the simulated residential use population was non-dietary ingestion exposure; whereas for the simulated general population, dietary exposure was the primary exposure route. Below the 95th percentile, the major exposure pathway was dietary for the general population; non-dietary ingestion was the major pathway starting below the 70th percentile for the residential use population. The new dermal absorption methodology considering surface loading had some impact, but did not change the order of key pathways. Published by Elsevier Ltd.

Pilot Study: Unique Response of Bone Tissue During an Investigation of Radio-Adaptive Effects in Mice

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Iwaniec, U.; Wu, H.

2011-01-01

PURPOSE: We obtained bone tissue to evaluate the collateral effects of experiments designed to investigate molecular mechanisms of radio-adaptation in a mouse model. Radio-adaptation describes a process by which the prior exposure to low dose radiation can protect against the toxic effect of a subsequent high dose exposure. In the radio-adaptation experiments, C57Bl/6 mice were exposed to either a Sham or a priming Low Dose (5 cGy) of Cs-137 gamma rays before being exposed to either a Sham or High Dose (6 Gy) 24 hours later. ANALYSIS: Bone tissue were obtained from two experiments where mice were sacrificed at 3 days (n=3/group, 12 total) and at 14 days (n=6/group, 24 total) following high dose exposure. Tissues were analyzed to 1) evaluate a radio-adaptive response in bone tissue and 2) describe cellular and microstructural effects for two skeletal sites with different rates of bone turnover. One tibia and one lumbar vertebrae (LV2), collected at the 3-day time-point, were analyzed by bone histomorphometry and micro-CT to evaluate the cellular response and any evidence of microarchitectural impact. Likewise, tibia and LV2, collected at the 14-day time-point, were analyzed by micro-CT alone to evaluate resulting changes to bone structure and microarchitecture. The data were analyzed by 2-way ANOVA to evaluate the effects of the priming low dose radiation, of the high dose radiation, and of any interaction between the priming low and high doses of radiation. Bone histomorphometry was performed in the cancellous bone (aka trabecular bone) compartments of the proximal tibial metaphysis and of LV2. RESULTS: Cellular Response @ 3 Days The priming Low Dose radiation decreased osteoblast-covered bone perimeter in the proximal tibia and the total cell density in the bone marrow in the LV2. High Dose radiation, regardless of prior exposure to priming dose, dramatically reduced total cell density in bone marrow of both the long bone and vertebra. However, in the proximal tibia, High Dose radiation increased the osteoclast-covered bone perimeters, the density of adipocytes in bone marrow, and the area of bone marrow occupied by fat cells -- while in the LV2, adipocytes were rare and not stimulated by High Dose radiation. In an unexpected response, High Dose radiation dramatically increased (10-fold) osteoblast-covered bone perimeter in the LV2.

[Effect of polychromatic visible light combined with infrared radiation on tumorigenicity of murine hepatoma cells and their sensitivity to lytic activity of natural killers].

PubMed

Filatova, N A; Kniazev, N A; Kosheverova, V V; Shatrova, A N; Samoĭlova, K A

2013-01-01

Tumorigenicity of murine hepatoma cells (MH22a) and their sensitivity to lysis by natural killers (NKs) have been studied after exposure to polychromatic visible and infrared light (VIS-IR, 480-3400 nm, 40 mW/cm2), similar to the terrestrial solar spectrum without its minor UV component, in order to elucidate the involvement of this important environmental and physiotherapeutic factor in regulation of the anti-tumor defense system. The MH22 cells were in vitro exposed to VIS-IR light and their sensitivity to lytic activity of NKs was evaluated. We found that sensitivity of MH22a cells to lysis by NKs after exposure to VIS-IR light at a dose of 4.8 J/cm2 increased 1.5-2 times, while it did not change after exposure to a dose of 9.6 J/cm2 at all ratios (1 : 5-1 : 50) of the number of NKs (effectors) to that of hepatoma cells (targets). The increase in the sensitivity of hepatoma cells to NKs was accompanied by structural changes of cell surface: the capability of supramembraneous glycoproteins (glycocalix) to sorb the vital dye alcian blue (AB) was significantly lower as compared with the unexposed cells of control group. However, no changes in AB sorption was revealed in hepatoma cells exposed to the light at a dose 9.6 J/cm2. Tumorigenicity of photo-irradiated MH22a cells has been studied in the in vivo experiments. Light-exposed (4.8 and 9.6 J/cm2) and intact hepatoma cells were transplanted into syngenic mice C3HA. Tumor volumes 25 days after transplantation proved to be smaller after exposure to the light at both doses than in the control group (4-4.5 times and 2.5-4 times, respectively), which correlated with the increase in the sensitivity to lisys by NKs and decrease in the AB sorption only after light exposure at dose 4.8 J/cm2. Using the flow cytometry method we could show that VIS-IR light at the applied doses did not interfere with the distribution of hepatoma cells over the cycle phases and thus deceleration of the tumor growth was not associated with cytostatic effect of VIS-IR light. To evaluate effect of polychromatic light on the growth of the preformed tumors, the 5-day course of daily light exposures of tumor bearing mice C3HA was carried out in 10 days after subcutaneous transplantation of 2 x 10(5) cells of syngene hepatoma when the tumors had developed in 100% animals. Like in the case of transplantation of the light-exposed cells, irradiation of the tumor bearing mice at doses 4.8-9.6 J/cm2 resulted in deceleration of tumor growth (2.1-2.9 and 2.2 times respectively) for 4 weeks as compared with non-irradiated mice.

Comparison in vivo Study of Genotoxic Action of High- Versus Very Low Dose-Rate γ-Irradiation

PubMed Central

Osipov, A. N.; Klokov, D. Y.; Elakov, A. L.; Rozanova, O. M.; Zaichkina, S. I.; Aptikaeva, G. F.; Akhmadieva, A. Kh.

2004-01-01

The aim of the present study was to compare genotoxicity induced by high- versus very low dose-rate exposure of mice to γ-radiation within a dose range of 5 to 61 cGy using the single-cell gel electrophoresis (comet) assay and the micronucleus test. CBA/lac male mice were irradiated at a dose rate of 28.2 Gy/h (high dose rate) or 0.07 mGy/h (very low dose rate). The comet assay study on spleen lymphocytes showed that very low dose-rate irradiation resulted in a statistically significant increase in nucleoid relaxation (DNA breaks), starting from a dose of 20 cGy. Further prolongation of exposure time and, hence, increase of a total dose did not, however, lead to further increase in the extent of nucleoid relaxation. Doses of 20 and 61 cGy were equal in inducing DNA breaks in mouse spleen lymphocytes as assayed by the comet assay. Of note, the level of DNA damage by 20–61 cGy doses of chronic irradiation (0.07 mGy/h) was similar to that an induced by an acute (28.2 Gy/h) dose of 14 cGy. The bone marrow micronucleus test revealed that an increase in polychromatic erythrocytes with micronuclei over a background level was induced by very low-level γ-irradiation with a dose of 61 cGy only, with the extent of the cytogenetic effect being similar to that of 10 cGy high-dose-rate exposure. In summary, presented results support the hypothesis of the nonlinear threshold nature of mutagenic action of chronic low dose-rate irradiation. PMID:19330145

Thyroid cancer following nuclear tests in French Polynesia

PubMed Central

de Vathaire, F; Drozdovitch, V; Brindel, P; Rachedi, F; Boissin, J-L; Sebbag, J; Shan, L; Bost-Bezeaud, F; Petitdidier, P; Paoaafaite, J; Teuri, J; Iltis, J; Bouville, A; Cardis, E; Hill, C; Doyon, F

2010-01-01

Background: Between 1966 and 1974, France conducted 41 atmospheric nuclear tests in Polynesia, but their potential health effects have not previously been investigated. Methods: In a case–control study, we compared the radiation exposure of almost all the French Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 (n=229) to the exposure of 373 French Polynesian control individuals without cancer from the general population. Radiation exposures were estimated using measurements after the nuclear tests, age at time of each test, residential and dietary information. Results: The average thyroid dose before 15 years of age was about 1.8 mGy, and 5% of the cases and 3% of the controls received a dose above 10 mGy. Despite this low level of dose, and after adjusting for ethnic group, level of education, body surface area, family history of thyroid cancer and number of pregnancies for women, we observed an increasing risk (P=0.04) of thyroid cancer with increasing thyroid dose received before age of 15 years, which remained after excluding non-aggressive differentiated thyroid micro-carcinomas. This increase of risk per unit of thyroid radiation dose was higher (P=0.03) in women who later experienced four or more pregnancies than among other women. Conclusion: The risk estimate is low, but is based on limited exposure data. The release of information on exposure, currently classified, would greatly improve the reliability of the risk estimation. PMID:20808313

Sun-Induced Changes in Stratum Corneum Function Are Gender and Dose Dependent in a Chinese Population

PubMed Central

Liu, Z.; Fluhr, J.W.; Song, S.P.; Sun, Z.; Wang, H.; Shi, Y.J.; Elias, P.M.; Man, M.-Q.

2010-01-01

Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18–50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure. PMID:20571289

Clinical outcomes and cost minimization with an alternative dosing regimen for meropenem in a community hospital.

PubMed

Patel, Gita Wasan; Duquaine, Susan M; McKinnon, Peggy S

2007-12-01

To compare outcomes and cost for the traditional United States Food and Drug Administration-approved dosing regimen for meropenem versus an alternative dosing regimen providing similar pharmacodynamic exposure with a lower total daily dose. Retrospective cohort study with a cost-minimization analysis. A 417-bed, privately owned community hospital. One hundred patients who received meropenem 1 g every 8 or 12 hours (traditional dosing regimen) between January 1 and September 30, 2004 (historical controls), and 192 patients who received meropenem 500 mg every 6 or 8 hours (alternative dosing regimen) between October 1, 2004, and September 30, 2005. Demographic and clinical data were collected for all patients. Cost-minimization analysis was performed by using the drug acquisition cost for meropenem. Demographics, sources of infection, distributions of organisms, and Charlson Comorbidity Index scores were similar between patients in the traditionally and alternatively dosed groups. Concomitant therapy, duration of therapy, success rates, lengths of stay, and in-hospital mortality rates were also similar between groups. Median time to the resolution of symptoms was 3 days for traditional dosing and 1.5 days for alternative dosing (p<0.0001). A logistic regression model including the dosing strategy showed that only polymicrobial infections and sepsis were associated with increased failure rates. The median cost for antibiotics was $439.05/patient for traditional dosing and $234.08/patient for alternative dosing (p<0.0001). An alternative dosing regimen for meropenem with a lower total daily dose yielded patient outcomes, including success rates and duration of therapy, equivalent to those of the traditional dosing regimen. Alternative dosing decreased total drug exposure, costs for antibiotics, and time to the resolution of infections.

Skin autofluorescence reflects individual seasonal UV exposure, skin photodamage and skin cancer development in organ transplant recipients.

PubMed

Togsverd-Bo, Katrine; Philipsen, Peter Alshede; Hædersdal, Merete; Wulf, Hans Christian Olsen

2018-01-01

Ultraviolet radiation (UVR)-induced skin cancers varies among organ transplant recipients (OTRs). To improve individual risk assessment of skin cancer, objectively quantified skin photodamage is needed. We measured personal UVR-exposure dose in OTRs and assessed the relation between individual UVR exposure, skin cancer and objectively measured photodamage in terms of skin autofluorescence, pigmentation, and black light-evaluated solar lentigines. Danish OTRs with (n=15) and without a history of skin cancer (n=15) kept sun diaries from May to September and wore personal dosimeters recording time-stamped UVR doses in standard erythema doses (SED). Photodamage was quantified as skin autofluorescence with excitation at 370nm (F370) and 430nm (F430), skin pigmentation (pigment protection factor, PPF), and black light-evaluated solar lentigines. OTRs with skin cancer received a higher UVR dose than OTRs without skin cancer (median 116 SED vs. 67 SED, p=0.07) and UVR exposure doses were correlated with increased PPF (p=0.052) and F370 on the shoulder (F370 shoulder ) (p=0.04). We found that skin cancer was associated with F370 shoulder (OR 10.53, CI 3.3-31,938; p=0.018) and time since transplantation (OR 1.34, CI 0.95-1.91, p=0.097). A cut-off at 7.2 arbitrary units, 89% of OTRs with skin cancer had F370 shoulder values above 7.2 arbitrary units and F370 shoulder was additionally related to patient age (p=0.09) and black light-evaluated solar lentigines (p=0.04). F370 autofluorescence indicates objectively measured photodamage and may be used for individual risk assessment of skin cancer development in OTRs. Copyright © 2017. Published by Elsevier B.V.

Radiation dose reduction efficiency of buildings after the accident at the Fukushima Daiichi Nuclear Power Station.

PubMed

Monzen, Satoru; Hosoda, Masahiro; Osanai, Minoru; Tokonami, Shinji

2014-01-01

Numerous radionuclides were released from the Fukushima Daiichi Nuclear Power Station (F1-NPS) in Japan following the magnitude 9.0 earthquake and tsunami on March 11, 2011. Local residents have been eager to calculate their individual radiation exposure. Thus, absorbed dose rates in the indoor and outdoor air at evacuation sites in the Fukushima Prefecture were measured using a gamma-ray measuring devices, and individual radiation exposure was calculated by assessing the radiation dose reduction efficiency (defined as the ratio of absorbed dose rate in the indoor air to the absorbed dose rate in the outdoor air) of wood, aluminum, and reinforced concrete buildings. Between March 2011 and July 2011, dose reduction efficiencies of wood, aluminum, and reinforced concrete buildings were 0.55 ± 0.04, 0.15 ± 0.02, and 0.19 ± 0.04, respectively. The reduction efficiency of wood structures was 1.4 times higher than that reported by the International Atomic Energy Agency. The efficiency of reinforced concrete was similar to previously reported values, whereas that of aluminum structures has not been previously reported. Dose reduction efficiency increased in proportion to the distance from F1-NPS at 8 of the 18 evacuation sites. Time variations did not reflect dose reduction efficiencies at evacuation sites although absorbed dose rates in the outdoor air decreased. These data suggest that dose reduction efficiency depends on structure types, levels of contamination, and evacuee behaviors at evacuation sites.

A Comparison of Molecular and Histopathological Changes in Mouse Intestinal Tissue Following Whole-Body Proton- or Gamma-Irradiation

NASA Technical Reports Server (NTRS)

Purgason, Ashley; Mangala, Lingegowda; Zhang, Ye; Hamilton, Stanley; Wu, Honglu

2010-01-01

There are many consequences following exposure to the space radiation environment which can adversely affect the health of a crew member. Acute radiation syndrome (ARS) involving nausea and vomiting, damage to radio-sensitive tissue such as the blood forming organs and gastrointestinal tract, and cancer are some of these negative effects. The space radiation environment is ample with protons and contains gamma rays as well. Little knowledge exists to this point, however, regarding the effects of protons on mammalian systems; conversely several studies have been performed observing the effects of gamma rays on different animal models. For the research presented here, we wish to compare our previous work looking at whole-body exposure to protons using a mouse model to our studies of mice experiencing whole-body exposure to gamma rays as part of the radio-adaptive response. Radio-adaptation is a well-documented phenomenon in which cells exposed to a priming low dose of radiation prior to a higher dose display a reduction in endpoints like chromosomal aberrations, cell death, micronucleus formation, and more when compared to their counterparts receiving high dose-irradiation only. Our group has recently completed a radio-adaptive experiment with C57BL/6 mice. For both this study and the preceding proton research, the gastrointestinal tract of each animal was dissected four hours post-irradiation and the isolated small intestinal tissue was fixed in formalin for histopathological examination or snap-frozen in liquid nitrogen for RNA isolation. Histopathologic observation of the tissue using standard H&E staining methods to screen for morphologic changes showed an increase in apoptotic lesions for even the lowest doses of 0.1 Gy of protons and 0.05 Gy of gamma rays, and the percentage of apoptotic cells increased with increasing dose. A smaller percentage of crypts showed 3 or more apoptotic lesions in animals that received 6 Gy of gamma-irradiation compared to mice receiving only 2 Gy of protons. Tissue of the gastrointestinal tract was also homogenized and RNA was isolated for cDNA synthesis and real-time PCR analysis. Inspecting apoptotic lesions of the duodenum of the small intestine as an endpoint of damage did not reveal a radio-adaptive response in C57BL/6 mice at the four hour time point. Results of gene expression changes showed consistent up or down regulation of a number of genes for all of the exposure doses that may play a role in proton-induced apoptosis. Preliminary results of gene expression alterations as a result of gamma-irradiation revealed a wealth of genes involved in oxidative stress and antioxidant defense processes being up- or down-regulated only at the highest exposure dose of 6 Gy and the combined dose of 5 cGy with 6 Gy. Those animals undergoing only 5 cGy of gamma-irradiation showed very little modification of gene expression. Taken together these results lead us to conclude that protons cause more severe morphologic damage to the duodenum of the small intestine at a dose of 2 Gy than a higher dose of 6 Gy of gamma rays to the same organ. Both protons and gamma rays lead to significant variation in gene expression at high doses in the small intestine and these changes may provide insight into the mechanism of injury seen in the gastrointestinal tract following radiation exposure. Astronauts experiencing prolonged exposure to protons in the low Earth orbit and in deep space, and experiencing acute exposure to protons from solar particle events, may face biological consequences that will impact a mission s success. We will continue this work by studying, quantifying, and comparing damage due to protons and gamma rays in the small intestine as well as other organs in a time-dependent manner.

Animal Studies of Residual Hematopoietic and Immune System Injury from Low Dose/Low Dose Rate Radiation and Heavy Metals.

DTIC Science & Technology

1998-09-01

accidents and industrial accidents (e.g., Chernobyl ) who receive high doses of radiation over a relatively short period of time, there are thousands of...several years after exposure may have been terminated. Examples of such groups include those affected by the fallout near Chernobyl , those living near...cohorts (e.g., Chernobyl victims) particular damage from low dose irradiation, especially membrane damage and mismatched DNA repair. Dosimetric Problems

Reproduction in the freshwater crustacean Asellus aquaticus along a gradient of radionuclide contamination at Chernobyl.

PubMed

Fuller, Neil; Ford, Alex T; Nagorskaya, Liubov L; Gudkov, Dmitri I; Smith, Jim T

2018-07-01

Nuclear accidents such as Chernobyl and Fukushima have led to contamination of the environment that will persist for many years. The consequences of chronic low-dose radiation exposure for non-human organisms inhabiting contaminated environments remain unclear. In radioecology, crustaceans are important model organisms for the development of environmental radioprotection. Previous laboratory studies have demonstrated deleterious effects of radiation exposure on crustacean reproduction. However, no studies have documented the effects of chronic radiation exposure on the reproduction of natural crustacean populations. Based on data from laboratory exposures, we hypothesised that populations of the freshwater isopod Asellus aquaticus exposed to radiation for thirty years at Chernobyl would display reduced reproductive output and altered timing of reproduction. To test this hypothesis, A. aquaticus was collected from six lakes at Chernobyl over two years with total dose rates ranging from 0.06-27.1μGy/h. No significant differences in the fecundity, mass of broods or proportion of reproducing female A. aquaticus were recorded. Significant differences in the body mass of gravid females were recorded suggesting different timings of reproduction, however this was not related to radiation contamination. No significant effect of a range of environmental parameters on A. aquaticus reproduction was recorded. Our data suggests current dose rates at Chernobyl are not causing discernible effects on the reproductive output of A. aquaticus. This study is the first to assess the effects of chronic low-dose radiation exposure on the reproductive output of an aquatic invertebrate at Chernobyl. These findings are consistent with proposed radiological protection benchmarks for the maintenance of wildlife populations and will assist in management of environments impacted by radiation. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of methylmercury and alcohol exposure in Drosophila melanogaster: Potential risks in neurodevelopmental disorders.

PubMed

Chauhan, Ved; Chauhan, Abha

2016-06-01

Extensive evidence suggests the role of oxidative stress in autism and other neurodevelopmental disorders. In this study, we investigated whether methylmercury (MeHg) and/or alcohol exposure has deleterious effects in Drosophila melanogaster (fruit flies). A diet containing different concentrations of MeHg in Drosophila induced free radical generation and increased lipid peroxidation (markers of oxidative stress) in a dose-dependent manner. This effect of MeHg on oxidative stress was enhanced by further exposure to alcohol. It was observed that alcohol alone could also induce free radical generation in flies. After alcohol exposure, MeHg did not affect the immobilization of flies, but it increased the recovery time in a concentration-dependent manner. MeHg significantly inhibited the activity of alcohol dehydrogenase (ADH) in a dose-dependent manner. Linear regression analysis showed a significant negative correlation between ADH activity and recovery time upon alcohol exposure in the flies fed a diet with MeHg. This relationship between ADH activity and recovery time after alcohol exposure was confirmed by adding 4-methyl pyrazole (an inhibitor of ADH) to the diet for the flies. These results suggest that consumption of alcohol by pregnant mothers who are exposed to MeHg may lead to increased oxidative stress and to increased length of time for alcohol clearance, which may have a direct impact on the development of the fetus, thereby increasing the risk of neurodevelopmental disorders. Published by Elsevier Ltd.

Estimated dose rates to members of the public from external exposure to patients with 131I thyroid treatment

DOE PAGES

Dewji, S.; Bellamy, M.; Hertel, N.; ...

2015-03-25

The purpose of this study is to estimate dose rates that may result from exposure to patients who had been administered iodine-131 ( 131I) as part of medical therapy were calculated. These effective dose rate estimates were compared with simplified assumptions under United States Nuclear Regulatory Commission Regulatory Guide 8.39, which does not consider body tissue attenuation nor time-dependent redistribution and excretion of the administered 131I. Methods: Dose rates were estimated for members of the public potentially exposed to external irradiation from patients recently treated with 131I. Tissue attenuation and iodine biokinetics were considered in the patient in a largermore » comprehensive effort to improve external dose rate estimates. The external dose rate estimates are based on Monte Carlo simulations using the Phantom with Movable Arms and Legs (PIMAL), previously developed by Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission. PIMAL was employed to model the relative positions of the 131I patient and members of the public in three exposure scenarios: (1) traveling on a bus in a total of six seated or standing permutations, (2) two nursing home cases where a caregiver is seated at 30 cm from the patient’s bedside and a nursing home resident seated 250 cm away from the patient in an adjacent bed, and (3) two hotel cases where the patient and a guest are in adjacent rooms with beds on opposite sides of the common wall, with the patient and guest both in bed and either seated back-to-back or lying head to head. The biokinetic model predictions of the retention and distribution of 131I in the patient assumed a single voiding of urinary bladder contents that occurred during the trip at 2, 4, or 8 h after 131I administration for the public transportation cases, continuous first-order voiding for the nursing home cases, and regular periodic voiding at 4, 8, or 12 h after administration for the hotel room cases. Organ specific activities of 131I in the thyroid, bladder, and combined remaining tissues were calculated as a function of time after administration. Exposures to members of the public were considered for 131I patients with normal thyroid uptake (peak thyroid uptake of ~27% of administered 131I), differentiated thyroid cancer (DTC, 5% uptake), and hyperthyroidism (80% uptake). Results: The scenario with the patient seated behind the member of the public yielded the highest dose rate estimate of seated public transportation exposure cases. The dose rate to the adjacent room guest was highest for the exposure scenario in which the hotel guest and patient are seated by a factor of ~4 for the normal and differentiated thyroid cancer uptake cases and by a factor of ~3 for the hyperthyroid case. Conclusions: It was determined that for all modeled cases, the DTC case yielded the lowest external dose rates, whereas the hyperthyroid case yielded the highest dose rates. In estimating external dose to members of the public from patients with 131I therapy, consideration must be given to (patient- and case-specific) administered 131I activities and duration of exposure for a more complete estimate. The method implemented here included a detailed calculation model, which provides a means to determine dose rate estimates for a range of scenarios. Finally, the method was demonstrated for variations of three scenarios, showing how dose rates are expected to vary with uptake, voiding pattern, and patient location.« less

Estimated dose rates to members of the public from external exposure to patients with 131I thyroid treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dewji, S.; Bellamy, M.; Hertel, N.

The purpose of this study is to estimate dose rates that may result from exposure to patients who had been administered iodine-131 ( 131I) as part of medical therapy were calculated. These effective dose rate estimates were compared with simplified assumptions under United States Nuclear Regulatory Commission Regulatory Guide 8.39, which does not consider body tissue attenuation nor time-dependent redistribution and excretion of the administered 131I. Methods: Dose rates were estimated for members of the public potentially exposed to external irradiation from patients recently treated with 131I. Tissue attenuation and iodine biokinetics were considered in the patient in a largermore » comprehensive effort to improve external dose rate estimates. The external dose rate estimates are based on Monte Carlo simulations using the Phantom with Movable Arms and Legs (PIMAL), previously developed by Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission. PIMAL was employed to model the relative positions of the 131I patient and members of the public in three exposure scenarios: (1) traveling on a bus in a total of six seated or standing permutations, (2) two nursing home cases where a caregiver is seated at 30 cm from the patient’s bedside and a nursing home resident seated 250 cm away from the patient in an adjacent bed, and (3) two hotel cases where the patient and a guest are in adjacent rooms with beds on opposite sides of the common wall, with the patient and guest both in bed and either seated back-to-back or lying head to head. The biokinetic model predictions of the retention and distribution of 131I in the patient assumed a single voiding of urinary bladder contents that occurred during the trip at 2, 4, or 8 h after 131I administration for the public transportation cases, continuous first-order voiding for the nursing home cases, and regular periodic voiding at 4, 8, or 12 h after administration for the hotel room cases. Organ specific activities of 131I in the thyroid, bladder, and combined remaining tissues were calculated as a function of time after administration. Exposures to members of the public were considered for 131I patients with normal thyroid uptake (peak thyroid uptake of ~27% of administered 131I), differentiated thyroid cancer (DTC, 5% uptake), and hyperthyroidism (80% uptake). Results: The scenario with the patient seated behind the member of the public yielded the highest dose rate estimate of seated public transportation exposure cases. The dose rate to the adjacent room guest was highest for the exposure scenario in which the hotel guest and patient are seated by a factor of ~4 for the normal and differentiated thyroid cancer uptake cases and by a factor of ~3 for the hyperthyroid case. Conclusions: It was determined that for all modeled cases, the DTC case yielded the lowest external dose rates, whereas the hyperthyroid case yielded the highest dose rates. In estimating external dose to members of the public from patients with 131I therapy, consideration must be given to (patient- and case-specific) administered 131I activities and duration of exposure for a more complete estimate. The method implemented here included a detailed calculation model, which provides a means to determine dose rate estimates for a range of scenarios. Finally, the method was demonstrated for variations of three scenarios, showing how dose rates are expected to vary with uptake, voiding pattern, and patient location.« less

Assessment of toxicity and potential risk of the anticoagulant rodenticide diphacinone using Eastern screech-owls (Megascops asio).

PubMed

Rattner, Barnett A; Horak, Katherine E; Lazarus, Rebecca S; Eisenreich, Karen M; Meteyer, Carol U; Volker, Steven F; Campton, Christopher M; Eisemann, John D; Johnston, John J

2012-04-01

In the United States, new regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides. This action may be offset by expanded use of first-generation compounds (e.g., diphacinone; DPN). Single-day acute oral exposure of adult Eastern screech-owls (Megascops asio) to DPN evoked overt signs of intoxication, coagulopathy, histopathological lesions (e.g., hemorrhage, hepatocellular vacuolation), and/or lethality at doses as low as 130 mg/kg body weight, although there was no dose-response relation. However, this single-day exposure protocol does not mimic the multiple-day field exposures required to cause mortality in rodent pest species and non-target birds and mammals. In 7-day feeding trials, similar toxic effects were observed in owls fed diets containing 2.15, 9.55 or 22.6 ppm DPN, but at a small fraction (<5%) of the acute oral dose. In the dietary trial, the average lowest-observed-adverse-effect-level for prolonged clotting time was 1.68 mg DPN/kg owl/week (0.24 mg/kg owl/day; 0.049 mg/owl/day) and the lowest lethal dose was 5.75 mg DPN/kg owl/week (0.82 mg/kg owl/day). In this feeding trial, DPN concentration in liver ranged from 0.473 to 2.21 μg/g wet weight, and was directly related to the daily and cumulative dose consumed by each owl. A probabilistic risk assessment indicated that daily exposure to as little as 3-5 g of liver from DPN-poisoned rodents for 7 days could result in prolonged clotting time in the endangered Hawaiian short-eared owl (Asio flammeus sandwichensis) and Hawaiian hawk (Buteo solitarius), and daily exposure to greater quantities (9-13 g of liver) could result in low-level mortality. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Assessment of toxicity and potential risk of the anticoagulant rodenticide diphacinone using Eastern screech-owls (Megascops asio)

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Lazarus, Rebecca S.; Eisenreich, Karen M.; Meteyer, Carol U.; Volker, Steven F.; Campton, Christopher M.; Eisemann, John D.; Johnston, John J.

2012-01-01

In the United States, new regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides. This action may be offset by expanded use of first-generation compounds (e.g., diphacinone; DPN). Single-day acute oral exposure of adult Eastern screech-owls (Megascops asio) to DPN evoked overt signs of intoxication, coagulopathy, histopathological lesions (e.g., hemorrhage, hepatocellular vacuolation), and/ or lethality at doses as low as 130 mg/kg body weight, although there was no dose-response relation. However, this single-day exposure protocol does not mimic the multiple-day field exposures required to cause mortality in rodent pest species and non-target birds and mammals. In 7-day feeding trials, similar toxic effects were observed in owls fed diets containing 2.15, 9.55 or 22.6 ppm DPN, but at a small fraction (<5%) of the acute oral dose. In the dietary trial, the average lowest-observed-adverse-effect-level for prolonged clotting time was 1.68 mg DPN/kg owl/week (0.24 mg/kg owl/day; 0.049 mg/owl/day) and the lowest lethal dose was 5.75 mg DPN/kg owl/week (0.82 mg/kg owl/day). In this feeding trial, DPN concentration in liver ranged from 0.473 to 2.21 μg/g wet weight, and was directly related to the daily and cumulative dose consumed by each owl. A probabilistic risk assessment indicated that daily exposure to as little as 3-5 g of liver from DPN-poisoned rodents for 7 days could result in prolonged clotting time in the endangered Hawaiian shorteared owl (Asio flammeus sandwichensis) and Hawaiian hawk (Buteo solitarius), and daily exposure to greater quantities (9-13 g of liver) could result in low-level mortality. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Clinical progression of ocular injury following arsenical vesicant lewisite exposure.

PubMed

Tewari-Singh, Neera; Croutch, Claire R; Tuttle, Richard; Goswami, Dinesh G; Kant, Rama; Peters, Eric; Culley, Tara; Ammar, David A; Enzenauer, Robert W; Petrash, J Mark; Casillas, Robert P; Agarwal, Rajesh

2016-12-01

Ocular injury by lewisite (LEW), a potential chemical warfare and terrorist agent, results in edema of eyelids, inflammation, massive corneal necrosis and blindness. To enable screening of effective therapeutics to treat ocular injury from LEW, useful clinically-relevant endpoints are essential. Hence, we designed an efficient exposure system capable of exposing up to six New-Zealand white rabbits at one time, and assessed LEW vapor-induced progression of clinical ocular lesions mainly in the cornea. The right eye of each rabbit was exposed to LEW (0.2 mg/L) vapor for 2.5, 5.0, 7.5 and 10.0 min and clinical progression of injury was observed for 28 days post-exposure (dose-response study), or exposed to same LEW dose for 2.5 and 7.5 min and clinical progression of injury was observed for up to 56 days post-exposure (time-response study); left eye served as an unexposed control. Increasing LEW exposure caused corneal opacity within 6 h post-exposure, which increased up to 3 days, slightly reduced thereafter till 3 weeks, and again increased thereafter. LEW-induced corneal ulceration peaked at 1 day post-exposure and its increase thereafter was observed in phases. LEW exposure induced neovascularization starting at 7 days which peaked at 22-35 days post-exposure, and remained persistent thereafter. In addition, LEW exposure caused corneal thickness, iris redness, and redness and swelling of the conjunctiva. Together, these findings provide clinical sequelae of ocular injury following LEW exposure and for the first time establish clinically-relevant quantitative endpoints, to enable the further identification of histopathological and molecular events involved in LEW-induced ocular injury.

Adult Lead Exposure: Time for Change

PubMed Central

Schwartz, Brian S.; Hu, Howard

2007-01-01

We have assembled this mini-monograph on adult lead exposure to provide guidance to clinicians and public health professionals, to summarize recent thinking on lead biomarkers and their relevance to epidemiologic research, and to review two key lead-related outcomes, namely, cardiovascular and cognitive. The lead standards of the U.S. Occupational Safety and Health Administration are woefully out of date given the growing evidence of the health effects of lead at levels of exposure previously thought to be safe, particularly newly recognized persistent or progressive effects of cumulative dose. The growing body of scientific evidence suggests that occupational standards should limit recent dose to prevent the acute effects of lead and separately limit cumulative dose to prevent the chronic effects of lead. We hope this mini-monograph will motivate renewed discussion of ways to protect lead-exposed adults in the United States and around the world. PMID:17431498

Transcriptomic profile of host response in mouse brain after exposure to plant toxin abrin.

PubMed

Bhaskar, A S Bala; Gupta, Nimesh; Rao, P V Lakshmana

2012-09-04

Abrin toxin is a plant glycoprotein, which is similar in structure and properties to ricin and is obtained from the seeds of Abrus precatorius (jequirity bean). Abrin is highly toxic, with an estimated human fatal dose of 0.1-1 μg/kg, and has caused death after accidental and intentional poisoning. Abrin is a potent biological toxin warfare agent. There are no chemical antidotes available against the toxin. Neurological symptoms like delirium, hallucinations, reduced consciousness and generalized seizures were reported in human poisoning cases. Death of a patient with symptoms of acute demyelinating encephalopathy with gastrointestinal bleeding due to ingestion of abrin seeds was reported in India. The aim of this study was to examine both dose and time-dependent transcriptional responses induced by abrin in the adult mouse brain. Mice (n=6) were exposed to 1 and 2 LD50 (2.83 and 5.66 μg/kg respectively) dose of abrin by intraperitoneal route and observed over 3 days. A subset of animals (n=3) were sacrificed at 1 and 2 day intervals for microarray and histopathology analysis. None of the 2 LD50 exposed animals survived till 3 days. The histopathological analysis showed the severe damage in brain and the infiltration of inflammatory cells in a dose and time dependent manner. The abrin exposure resulted in the induction of rapid immune and inflammatory response in brain. Clinical biochemistry parameters like lactate dehydrogenase, aspartate aminotransferase, urea and creatinine showed significant increase at 2-day 2 LD50 exposure. The whole genome microarray data revealed the significant regulation of various pathways like MAPK pathway, cytokine-cytokine receptor interaction, calcium signaling pathway, Jak-STAT signaling pathway and natural killer cell mediated toxicity. The comparison of differential gene expression at both the doses showed dose dependent effects of abrin toxicity. The real-time qRT-PCR analysis of selected genes supported the microarray data. This is the first report on host-gene response using whole genome microarray in an animal model after abrin exposure. The data generated provides leads for developing suitable medical counter measures against abrin poisoning. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs.

PubMed

Andreasen, Nancy C; Pressler, Marcus; Nopoulos, Peg; Miller, Del; Ho, Beng-Choon

2010-02-01

A standardized quantitative method for comparing dosages of different drugs is a useful tool for designing clinical trials and for examining the effects of long-term medication side effects such as tardive dyskinesia. Such a method requires establishing dose equivalents. An expert consensus group has published charts of equivalent doses for various antipsychotic medications for first- and second-generation medications. These charts were used in this study. Regression was used to compare each drug in the experts' charts to chlorpromazine and haloperidol and to create formulas for each relationship. The formulas were solved for chlorpromazine 100 mg and haloperidol 2 mg to derive new chlorpromazine and haloperidol equivalents. The formulas were incorporated into our definition of dose-years such that 100 mg/day of chlorpromazine equivalent or 2 mg/day of haloperidol equivalent taken for 1 year is equal to one dose-year. All comparisons to chlorpromazine and haloperidol were highly linear with R(2) values greater than .9. A power transformation further improved linearity. By deriving a unique formula that converts doses to chlorpromazine or haloperidol equivalents, we can compare otherwise dissimilar drugs. These equivalents can be multiplied by the time an individual has been on a given dose to derive a cumulative value measured in dose-years in the form of (chlorpromazine equivalent in mg) x (time on dose measured in years). After each dose has been converted to dose-years, the results can be summed to provide a cumulative quantitative measure of lifetime exposure. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Estimation of the total effective dose from low-dose CT scans and radiopharmaceutical administrations delivered to patients undergoing SPECT/CT explorations.

PubMed

Montes, Carlos; Tamayo, Pilar; Hernandez, Jorge; Gomez-Caminero, Felipe; García, Sofia; Martín, Carlos; Rosero, Angela

2013-08-01

Hybrid imaging, such as SPECT/CT, is used in routine clinical practice, allowing coregistered images of the functional and structural information provided by the two imaging modalities. However, this multimodality imaging may mean that patients are exposed to a higher radiation dose than those receiving SPECT alone. The study aimed to determine the radiation exposure of patients who had undergone SPECT/CT examinations and to relate this to the Background Equivalent Radiation Time (BERT). 145 SPECT/CT studies were used to estimate the total effective dose to patients due to both radiopharmaceutical administrations and low-dose CT scans. The CT contribution was estimated by the Dose-Length Product method. Specific conversion coefficients were calculated for SPECT explorations. The radiation dose from low-dose CTs ranged between 0.6 mSv for head and neck CT and 2.6 mSv for whole body CT scan, representing a maximum of 1 year of background radiation exposure. These values represent a decrease of 80-85% with respect to the radiation dose from diagnostic CT. The radiation exposure from radiopharmaceutical administration varied from 2.1 mSv for stress myocardial perfusion SPECT to 26 mSv for gallium SPECT in patients with lymphoma. The BERT ranged from 1 to 11 years. The contribution of low-dose CT scans to the total radiation dose to patients undergoing SPECT/CT examinations is relatively low compared with the effective dose from radiopharmaceutical administration. When a CT scan is only acquired for anatomical localization and attenuation correction, low-dose CT scan is justified on the basis of its lower dose.

Subchronic chloroform priming protects mice from a subsequently administered lethal dose of chloroform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Philip, Binu K.; Anand, Sathanandam S.; Palkar, Prajakta S.

2006-10-01

Protection offered by pre-exposure priming with a small dose of a toxicant against the toxic and lethal effects of a subsequently administered high dose of the same toxicant is autoprotection. Although autoprotection has been extensively studied with diverse toxicants in acute exposure regimen, not much is known about autoprotection after priming with repeated exposure. The objective of this study was to investigate this concept following repeated exposure to a common water contaminant, chloroform. Swiss Webster (SW) mice, exposed continuously to either vehicle (5% Emulphor, unprimed) or chloroform (150 mg/kg/day po, primed) for 30 days, were challenged with a normally lethalmore » dose of chloroform (750 mg chloroform/kg po) 24 h after the last exposure. As expected, 90% of the unprimed mice died between 48 and 96 h after administration of the lethal dose in contrast to 100% survival of mice primed with chloroform. Time course studies indicated lower hepato- and nephrotoxicity in primed mice as compared to unprimed mice. Hepatic CYP2E1, glutathione levels (GSH), and covalent binding of {sup 14}C-chloroform-derived radiolabel did not differ between livers of unprimed and primed mice after lethal dose exposure, indicating that protection in liver is neither due to decreased bioactivation nor increased detoxification. Kidney GSH and glutathione reductase activity were upregulated, with a concomitant reduction in oxidized glutathione in the primed mice following lethal dose challenge, leading to decreased renal covalent binding of {sup 14}C-chloroform-derived radiolabel, in the absence of any change in CYP2E1 levels. Buthionine sulfoximine (BSO) intervention led to 70% mortality in primed mice challenged with lethal dose. These data suggest that higher detoxification may play a role in the lower initiation of kidney injury observed in primed mice. Exposure of primed mice to a lethal dose of chloroform led to 40% lower chloroform levels (AUC{sub 15-360min}) in the systemic circulation. Exhalation of {sup 14}C-chloroform was unchanged in primed as compared to unprimed mice (AUC{sub 1-6h}). Urinary excretion of {sup 14}C-chloroform was higher in primed mice after administration of the lethal dose. However, neither slightly higher urinary elimination nor unchanged expiration can account for the difference in systemic levels of chloroform. Liver and kidney regeneration was inhibited by the lethal dose in unprimed mice leading to progressive injury, organ failure, and 90% mortality. In contrast, sustained and highly stimulated compensatory hepato- and nephrogenic repair prevented the progression of injury resulting in 100% survival of primed mice challenged with the lethal dose. These findings affirm the critical role of tissue regeneration and favorable detoxification (only in kidney) of the lethal dose of chloroform in subchronic chloroform priming-induced autoprotection.« less

Microbolometer SU-8 photoresist microstructure with cytochrome c protein as a sensing pixel for microbolometer

NASA Astrophysics Data System (ADS)

Lai, Jian-Lun; Su, Guo-Dung J.

2012-08-01

There are two important parts in Microbolometer: the high TCR sensing material and low thermal conductance. The high TCR material cytochrome c protein is a good candidate for infrared detection. Our group already demonstrated cytochrome c thin film has high TCR on the top of SU8 surface that has been published in Proc. of SPIE (2011). Because the very low thermal conductivity of SU-8, we proposed a new concept of SU-8 photoresist thermal insulation desk structure, and used the exposure dose method to establish it. Although exposure dose method is very sensitive to exposure time and PEB time, we successfully investigated the right recipe to create new desk insulation structure which with different height. We also explored the relationship between mask II exposure time and desktop thickness, and how the post-exposure baking (PEB) time influenced our structure. Our SU-8 photoresist insulation structure fabrication process is much easier and cheaper than present SiNx fabrication process. The desk shape structure can have low thermal conductance of 6.681*10-6 W/K. The easy-made SU-8 microstructures and cytochrome c thin films that and can reduce the cost of IR microbolometer. We believe that it is possible to fabricate a new generation of microbolometer based on cytochrome c protein and SU-8 photoresist microstructures.

Low and moderate prenatal ethanol exposures of mice during gastrulation or neurulation delays neurobehavioral development.

PubMed

Schambra, Uta B; Goldsmith, Jeff; Nunley, Kevin; Liu, Yali; Harirforoosh, Sam; Schambra, Heidi M

2015-01-01

Human and animal studies show significant delays in neurobehavioral development in offspring after prolonged prenatal exposure to moderate and high ethanol doses resulting in high blood alcohol concentration (BECs). However, none have investigated the effects of lower ethanol doses given acutely during specific developmental time periods. Here, we sought to create a mouse model for modest and circumscribed human drinking during the 3rd and 4th weeks of pregnancy. We acutely treated mice during embryo gastrulation on gestational day (GD) 7 or neurulation on GD8 with a low or moderate ethanol dose given via gavage that resulted in BECs of 107 and 177 mg/dl, respectively. We assessed neonatal physical development (pinnae unfolding, and eye opening); weight gain from postnatal day (PD) 3-65; and neurobehavioral maturation (pivoting, walking, cliff aversion, surface righting, vertical screen grasp, and rope balance) from PD3 to 17. We used a multiple linear regression model to determine the effects of dose, sex, day of treatment and birth in animals dosed during gastrulation or neurulation, relative to their vehicle controls. We found that ethanol exposure during both time points (GD7 and GD8) resulted in some delays of physical development and significant sensorimotor delays of pivoting, walking, and thick rope balance, as well as additional significant delays in cliff aversion and surface righting after GD8 treatment. We also found that treatment with the low ethanol dose more frequently affected neurobehavioral development of the surviving pups than treatment with the moderate ethanol dose, possibly due to a loss of severely affected offspring. Finally, mice born prematurely were delayed in their physical and sensorimotor development. Importantly, we showed that brief exposure to low dose ethanol, if administered during vulnerable periods of neuroanatomical development, results in significant neurobehavioral delays in neonatal mice. We thus expand concerns about alcohol consumption during the 3rd and 4th weeks of human pregnancy to include occasional light to moderate drinking. Copyright © 2015 Elsevier Inc. All rights reserved.

Chernobyl doses. Volume 1. Analysis of forest canopy radiation response from multispectral imagery and the relationship to doses. Technical report, 29 July 1987-30 September 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

McClennan, G.E.; Anno, G.H.; Whicker, F.W.

1994-09-01

This volume of the report Chernobyl Doses presents details of a new, quantitative method for remotely sensing ionizing radiation dose to vegetation. Analysis of Landsat imagery of the area within a few kilometers of the Chernobyl nuclear reactor station provides maps of radiation dose to pine forest canopy resulting from the accident of April 26, 1986. Detection of the first date of significant, persistent deviation from normal of the spectral reflectance signature of pine foliage produces contours of radiation dose in the 20 to 80 Gy range extending up to 4 km from the site of the reactor explosion. Themore » effective duration of exposure for the pine foliage is about 3 weeks. For this exposure time, the LD50 of Pinus sylvestris (Scotch pine) is about 23 Gy. The practical lower dose limit for the remote detection of radiation dose to pine foliage with the Landsat Thematic Mapper is about 5 Gy or 1/4 of the LD50.« less

Ultraviolet spectral distribution and erythema-weighted irradiance from indoor tanning devices compared with solar radiation exposures.

PubMed

Sola, Yolanda; Baeza, David; Gómez, Miguel; Lorente, Jerónimo

2016-08-01

Concern regarding the impact of indoor tanning devices on human health has led to different regulations and recommendations, which set limits on erythema-weighted irradiance. Here, we analyze spectral emissions from 52 tanning devices in Spanish facilities and compare them with surface solar irradiance for different solar zenith angles. Whereas most of the devices emitted less UV-B radiation than the midday summer sun, the unweighted UV-A irradiance was 2-6 times higher than solar radiation. Moreover, the spectral distributions of indoor devices were completely different from that of solar radiation, differing in one order of magnitude at some UV-A wavelengths, depending on the lamp characteristics. In 21% of the devices tested, the erythema-weighted irradiance exceeded 0.3Wm(-2): the limit fixed by the European standard and the Spanish regulation. Moreover, 29% of the devices fall within the UV type 4 classification, for which medical advice is required. The high variability in erythema-weighted irradiance results in a wide range of exposure times to reach 1 standard erythemal dose (SED: 100Jm(-2)), with 62% of devices requiring exposures of <10min to reach 1 SED. Nevertheless, the unweighted UV-A dose during this time period would be from 1.4 to 10.3 times more than the solar UV-A dose. Copyright © 2016 Elsevier B.V. All rights reserved.

Potentiometric Biosensor for Studying Hydroquinone Cytotoxicity in vitro

PubMed Central

Wang, Yanyan; Chen, Qiang; Zeng, Xiangqun

2009-01-01

Many processes in living cells have electrochemical characteristics that are suitable for measurement by potentiometric biosensors. Potentiometric biosensors allow non invasive, real-time monitoring of the extracellular environment changes by measuring the potential at cell/sensor interface. This can be used as an indicator for overall cell cytotoxicity. The present work employs a potentiometric sensor array to investigate the cytotoxicity of hydroquinone to cultured mammalian V79 cells. Various electrode substrates (Au, PPy-HQ and PPy-PS) used for cell growth were designed and characterized. The controllable release of hydroquinone from PPy substrates was studied. Our results showed that hydroquinone exposure affected cell proliferation and delayed cell growth and attachment in a dose-dependent manner. Additionally, we have shown that exposure of V79 cells to hydroquinone at low doses (i.e 5μM) for more than 15 hours allows V79 cells to gain enhanced adaptability to survive exposure to high toxic HQ doses afterwards. Compared with traditional methods, the potentiometric biosensor not only provides non-invasive and real time monitoring of the cellular reactions but also is more sensitive for in vitro cytotoxicity study. By real time and non-invasive monitoring of the extracellular potential in vitro, the potentiometric sensor system represents a promising biosensor system for drug discovery. PMID:19926470

A prospective case control comparison of the ZeroGravity system versus a standard lead apron as radiation protection strategy in neuroendovascular procedures.

PubMed

Haussen, Diogo C; Van Der Bom, Imramsjah Martijn John; Nogueira, Raul G

2016-10-01

We aimed to compare the performance of the ZeroGravity (ZG) system (radiation protection system composed by a suspended lead suit) against the use of standard protection (lead apron (LA), thyroid shield, lead eyeglasses, table skirts, and ceiling suspended shield) in neuroangiography procedures. Radiation exposure data were prospectively collected in consecutive neuroendovascular procedures between December 2014 and February 2015. Operator No 1 was assigned to the use of an LA (plus lead glasses, thyroid shield, and a 1 mm hanging shield at the groin) while operator No 2 utilized the ZG system. Dosimeters were used to measure peak skin dose for the head, thyroid, and left foot. The two operators performed a total of 122 procedures during the study period. The ZG operator was more commonly the primary operator compared with the LA operator (85% vs 71%; p=0.04). The mean anterior-posterior (AP), lateral, and cumulative dose area product (DAP) radiation exposure as well as the mean fluoroscopy time were not statistically different between the operators' cases. The peak skin dose to the head of the operator with LA was 2.1 times higher (3380 vs 1600 μSv), while the thyroid was 13.9 (4460 vs 320 μSv), the mediastinum infinitely (520 vs 0 μSv), and the foot 3.3 times higher (4870 vs 1470 μSv) compared with the ZG operator, leading to an overall accumulated dose 4 times higher. The ratio of cumulative operator received dose/total cumulative DAP was 2.5 higher on the LA operator. The ZG radiation protection system leads to substantially lower radiation exposure to the operator in neurointerventional procedures. However, substantial exposure may still occur at the level of the lens and thyroid to justify additional protection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

RECONSTRUCTION OF INDIVIDUAL DOSES DUE TO MEDICAL EXPOSURES FOR MEMBERS OF THE TECHA RIVER COHORT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shagina, N. B.; Golikov, V.; Degteva, M. O.

Purpose: To describe a methodology for reconstruction of doses due to medical exposures for members of the Techa River Cohort (TRC) who received diagnostic radiation at the clinic of the Urals Research Center for Radiation Medicine (URCRM) in 1952–2005. To calculate doses of medical exposure for the TRC members and compare with the doses that resulted from radioactive contamination of the Techa River. Material and Methods: Reconstruction of individual medical doses is based on data on x-ray diagnostic procedures available for each person examined at the URCRM clinics and values of absorbed dose in 12 organs per typical x-ray proceduremore » calculated with the use of a mathematical phantom. Personal data on x-ray diagnostic examinations have been complied in the computerized “Registry of x-ray diagnostic procedures.” Sources of information are archival registry books from the URCRM x-ray room (available since 1956) and records on x-ray diagnostic procedures in patient-case histories (since 1952). The absorbed doses for 12 organs of interest have been evaluated per unit typical x-ray procedure with account taken of the x-ray examination parameters characteristic for the diagnostic machines used at the URCRM clinics. These parameters have been evaluated from published data on technical characteristics of the x-ray diagnostic machines used at the URCRM clinics in 1952–1988 and taken from the x-ray room for machines used at the URCRM in 1989–2005. Absorbed doses in the 12 organs per unit typical x-ray procedure have been calculated with use of a special computer code, EDEREX, developed at the Saint-Petersburg Research Institute of Radiation Hygiene after Professor P.V. Ramzaev. Individual accumulated doses of medical exposure have been calculated with a computer code, MEDS (Medical Exposure Dosimetry System), specifically developed at the URCRM. Results: At present, the “Registry of x-ray diagnostic procedures” contains information on individual x-ray examinations for over 9,500 persons including 6,415 TRC members. Statistical analysis of the Registry data showed that the more frequent types of examinations were fluoroscopy and radiography of the chest and fluoroscopy of the stomach and the esophagus. Average absorbed doses accumulated by year 2005 calculated for the 12 organs varied from 4 mGy for testes to 40 mGy for bone surfaces. Maximum individual medical doses could reach 500–650 mGy and in some cases exceeded doses from exposure at the Techa River. Conclusions: For the first time the doses of medical exposure were calculated and analyzed for members of the Techa River Cohort who received diagnostic radiation at the URCRM clinics. These results are being used in radiation-risk analysis to adjust for this source of confounding exposure in the TRC.« less

Estimation of occupational cosmic radiation exposure among airline personnel: Agreement between a job-exposure matrix, aggregate, and individual dose estimates.

PubMed

Talibov, Madar; Salmelin, Raili; Lehtinen-Jacks, Susanna; Auvinen, Anssi

2017-04-01

Job-exposure matrices (JEM) are used for exposure assessment in occupational studies, but they can involve errors. We assessed agreement between the Nordic Occupational Cancer Studies JEM (NOCCA-JEM) and aggregate and individual dose estimates for cosmic radiation exposure among Finnish airline personnel. Cumulative cosmic radiation exposure for 5,022 airline crew members was compared between a JEM and aggregate and individual dose estimates. The NOCCA-JEM underestimated individual doses. Intraclass correlation coefficient was 0.37, proportion of agreement 64%, kappa 0.46 compared with individual doses. Higher agreement was achieved with aggregate dose estimates, that is annual medians of individual doses and estimates adjusted for heliocentric potentials. The substantial disagreement between NOCCA-JEM and individual dose estimates of cosmic radiation may lead to exposure misclassification and biased risk estimates in epidemiological studies. Using aggregate data may provide improved estimates. Am. J. Ind. Med. 60:386-393, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Dose-responsiveness and persistence of microRNA expression alterations induced by cigarette smoke in mouse lung.

PubMed

Izzotti, Alberto; Larghero, Patrizia; Longobardi, Mariagrazia; Cartiglia, Cristina; Camoirano, Anna; Steele, Vernon E; De Flora, Silvio

2011-12-01

Our previous studies demonstrated that exposure to cigarette smoke (CS), either mainstream or environmental, results in a remarkable downregulation of microRNA expression in the lung of both mice and rats. The goals of the present study were to evaluate the dose responsiveness to CS and the persistence of microRNA alterations after smoking cessation. ICR (CD-1) neonatal mice were exposed whole-body to mainstream CS, at the doses of 119, 292, 438, and 631mg/m(3) of total particulate matter. Exposure started within 12h after birth and continued daily for 4 weeks. The levels of bulky DNA adducts and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were measured by (32)P postlabeling procedures, and the expression of 697 mouse microRNAs was analyzed by microarray. The highest CS dose was lethal. Exposure to CS caused a dose-dependent increase of DNA alterations. DNA adducts and, even more sharply, 8-oxodGuo were reverted 1 and 4 weeks after smoking cessation. Exposure to CS resulted in an evident dysregulation of microRNA expression profiles, mainly in the sense of downregulation. The two lowest doses were not particularly effective, while the highest nonlethal dose produced extensive microRNA alterations. The expression of most downregulated microRNAs, including among others 7 members of the let-7 family, was restored one week after smoking cessation. However, the recovery was incomplete for a limited array of microRNAs, including mir-34b, mir-345, mir-421, mir-450b, mir-466, and mir-469. Thus, it appears that microRNAs mainly behave as biomarkers of effect and that exposure to high-dose, lasting for an adequate period of time, is needed to trigger the CS-related carcinogenesis process in the experimental animal model used. Copyright © 2011 Elsevier B.V. All rights reserved.

Mimicking the effects of spaceflight on bone: Combined effects of disuse and chronic low-dose rate radiation exposure on bone mass in mice.

PubMed

Yu, Kanglun; Doherty, Alison H; Genik, Paula C; Gookin, Sara E; Roteliuk, Danielle M; Wojda, Samantha J; Jiang, Zhi-Sheng; McGee-Lawrence, Meghan E; Weil, Michael M; Donahue, Seth W

2017-11-01

During spaceflight, crewmembers are subjected to biomechanical and biological challenges including microgravity and radiation. In the skeleton, spaceflight leads to bone loss, increasing the risk of fracture. Studies utilizing hindlimb suspension (HLS) as a ground-based model of spaceflight often neglect the concomitant effects of radiation exposure, and even when radiation is accounted for, it is often delivered at a high-dose rate over a very short period of time, which does not faithfully mimic spaceflight conditions. This study was designed to investigate the skeletal effects of low-dose rate gamma irradiation (8.5 cGy gamma radiation per day for 20 days, amounting to a total dose of 1.7 Gy) when administered simultaneously to disuse from HLS. The goal was to determine whether continuous, low-dose rate radiation administered during disuse would exacerbate bone loss in a murine HLS model. Four groups of 16 week old female C57BL/6 mice were studied: weight bearing + no radiation (WB+NR), HLS + NR, WB + radiation exposure (WB+RAD), and HLS+RAD. Surprisingly, although HLS led to cortical and trabecular bone loss, concurrent radiation exposure did not exacerbate these effects. Our results raise the possibility that mechanical unloading has larger effects on the bone loss that occurs during spaceflight than low-dose rate radiation. Copyright © 2017 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Radiation protection aspects of the cosmic radiation exposure of aircraft crew.

PubMed

Bartlett, D T

2004-01-01

Aircraft crew and frequent flyers are exposed to elevated levels of cosmic radiation of galactic and solar origin and secondary radiation produced in the atmosphere, the aircraft structure and its contents. Following recommendations of the International Commission on Radiological Protection in Publication 60, the European Union introduced a revised Basic Safety Standards Directive, which included exposure to natural sources of ionising radiation, including cosmic radiation, as occupational exposure. The revised Directive has been incorporated into laws and regulations in the European Union Member States. Where the assessment of the occupational exposure of aircraft crew is necessary, the preferred approach to monitoring is by the recording of staff flying times and calculated route doses. Route doses are to be validated by measurements. This paper gives the general background, and considers the radiation protection aspects of the cosmic radiation exposure of aircraft crew, with the focus on the situation in Europe.

Occupational Exposure to Diesel Motor Exhaust and Lung Cancer: A Dose-Response Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study

PubMed Central

Matrat, Mireille; Guida, Florence; Cénée, Sylvie; Févotte, Joelle; Carton, Matthieu; Cyr, Diane; Menvielle, Gwenn; Paget-Bailly, Sophie; Radoï, Loredana; Schmaus, Annie; Bara, Simona; Velten, Michel; Luce, Danièle; Stücker, Isabelle; The Icare Study Group

2015-01-01

Background. In a French large population-based case-control study we investigated the dose-response relationship between lung cancer and occupational exposure to diesel motor exhaust (DME), taking into account asbestos exposure. Methods. Exposure to DME was assessed by questionnaire. Asbestos was taken into account through a global indicator of exposure to occupational carcinogens or by a specific JEM. Results. We found a crude dose response relationship with most of the indicators of DME exposure, including with the cumulative exposure index. All results were affected by adjustment for asbestos exposure. The dose response relationships between DME and lung cancer were observed among subjects never exposed to asbestos. Conclusions. Exposure to DME and to asbestos is frequently found among the same subjects, which may explain why dose-response relationships in previous studies that adjusted for asbestos exposure were inconsistent. PMID:26425123

The use of TLD-700H dosemeters in the assessment of external doses at the former Semipalatinsk nuclear test site.

PubMed

Hill, P; Dederichs, H; Pillath, J; Schlecht, W; Hille, R; Artemev, O; Ptitskaya, L; Akhmetov, M

2002-01-01

The joint projects performed since 1995 by the Jülich Research Centre in co-operation with the Kazakh National Nuclear Centre in the area of the former nuclear test site near Semipalatinsk, in eastern Kazakhstan, have assessed the current dose rate of the population at and around the test site, as well as determining retrospectively the dose rate of persons affected by the atmospheric tests. Measurements of the population by personal dosemeters depend on reliably wearing these dosemeters over prolonged periods of time, and of a sufficient dosemeter return. In the past, such measurements have been particularly successful whenever short wearing times were possible. This requires high sensitivity of the dosemeters. The suitability of the highly sensitive TLD material of the BICRON TLD 700H type for such personal dosimetry measurements was investigated. It was tested in practical field application at the Semipalatinsk nuclear test site in September 2000. Initial results are available from individual doses received by a group of geologists and a group of herdsmen at the test site. For the first time, the individual dose was measured directly in these population groups. Detection limits below 1 microSv permit informative measurements for wearing times of less than two weeks. Most individual doses did not arise significantly out of local fluctuations of natural background. A conservative assessment from the aspect of practical health physics yielded a mean personal dose of 0.55 microSv per day for the herdsmen, whereas the geologists received a mean personal dose of 0.45 microSv per day. For an annual exposure period of typically, about three months, the radiation dose received by the persons investigated, in addition to the natural radiation exposure, is thus well below the international limit value of 1 mSv x a(-1) for the population dose.

Pharmacokinetics, Safety and Tolerability of Sacubitril/Valsartan (LCZ696) After Single-Dose Administration in Healthy Chinese Subjects.

PubMed

Han, Yi; Ayalasomayajula, Surya; Pan, Wei; Yang, Fan; Yuan, Yaozong; Langenickel, Thomas; Hinder, Markus; Kalluri, Sampath; Pal, Parasar; Sunkara, Gangadhar

2017-02-01

Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) and has been recently approved in several countries for the treatment of patients with heart failure and reduced ejection fraction. This was the first study conducted to characterise the pharmacokinetics of LCZ696 analytes (pro-drug sacubitril, active neprilysin inhibitor LBQ657 and valsartan) after single-dose administration of LCZ696 in healthy Chinese subjects. In this open-label, randomised, parallel-group study, following screening and baseline evaluation, eligible healthy subjects received single oral doses of LCZ696 50, 100, 200 or 400 mg. The pharmacokinetics, safety and tolerability of LCZ696 were assessed up to 72 h after dosing. A total of 40 healthy male subjects were enrolled, and all completed the study. Following oral administration, LCZ696 delivered systemic exposure to sacubitril, LBQ657 and valsartan with a median time to reach maximum plasma concentration (T max ) ranging from 0.50 to 1.25, 2.00 to 3.00 and 1.50 to 2.50 h, respectively, over the investigated dose range. The mean terminal elimination half-life (T 1/2 ) ranged from 0.89 to 1.35, 8.57 to 9.24 and 5.33 to 7.91 h for sacubitril, LBQ657 and valsartan, respectively. The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last ), and maximum plasma concentration (C max ) for LBQ657 increased dose proportionally over the entire dose range. Dose linear increase in the exposure was observed across the dose range for sacubitril and valsartan. LCZ696 was safe and well tolerated at all doses in this study. Adverse events of only mild intensity, which required no treatment, were reported in 6 (15 %) subjects. The pharmacokinetic profiles of LCZ696 analytes in Chinese subjects are similar to those reported previously in Caucasian subjects.

Blood clearance and occupational exposure for 177Lu-DOTATATE compared to 177Lu-PSMA radionuclide therapy.

PubMed

Abuqbeitah, Mohammad; Demir, Mustafa; Uslu-Beşli, Lebriz; Yeyin, Nami; Sönmezoğlu, Kerim

2018-03-01

The main target of this work is to examine blood clearance and external exposure for 177 Lu-DOTATATE compared with new emerging 177 Lu-PSMA therapy. Blood clearance and radiation exposure of 31 patients treated with 5.5 ± 1.1 GBq 177 Lu-DOTATATE were compared to those of 23 patients treated with 7.4 GBq 177 Lu-PSMA. Dose rates were measured at several distances and time points up to 120 h after treatment. Blood samples were collected conjunctively after infusion. Caregiver's cumulative dose was measured by means of an OSL (optically stimulated luminescence) dosimeter for 4-5 days and medical staff's dose was also estimated using electronic personal dosimeters. Finger dose was determined via ring TLD (Thermoluminescence Dosimeter) for radiopharmacists and nurses. Dose rates due to 177 Lu-DOTATATE at a distance of 1 m, 4 h and 6 h after infusion, were 3.0 ± 2.8 and 2 ± 1.9 µSv/(h GBq), respectively, while those due to 177 Lu-PSMA were 3.1 ± 0.8 and 2.2 ± 0.9 µSv/(h GBq). Total effective dose of 17 caregivers was 100-200 µSv for 177 Lu-DOTATATE therapy. Mean effective doses to nurses and radiopharmacists were 5 and 4 µSv per patient, respectively, while those for physicists and physicians were 2 µSv per patient. For 177 Lu-DOTATATE, effective half-life in blood and early elimination phase were 0.31 ± 0.13 and 4.5 ± 1 h, while they were found as 0.4 ± 0.1 and 5 ± 1 h, respectively, for 177 Lu-PSMA. The first micturition time following 177 Lu-DOTATATE infusion was noted after 36 ± 14 min, while the second and third voiding times were after 74 ± 9 and 128 ± 41 min, respectively. It is concluded that blood clearance and radiation exposure for 177 Lu-DOTATATE are very similar to those for 177 Lu-PSMA, and both treatment modalities are reasonably reliable for outpatient treatment, since the mean dose rate [2.1 µSv/(h GBq)] decreased below the dose rate that allows release of the patient from the hospital (20 µSv/h) after 6 h at 1 m distance.

Pharmacometrics-based dose selection of levofloxacin as a treatment for postexposure inhalational anthrax in children.

PubMed

Li, Fang; Nandy, Partha; Chien, Shuchean; Noel, Gary J; Tornoe, Christoffer W

2010-01-01

Levofloxacin was recently (May 2008) approved by the U.S. Food and Drug Administration as a treatment for children following inhalational exposure to anthrax. Given that no clinical trials to assess the efficacy of a chosen dose was conducted, the basis for the dose recommendation was based upon pharmacometric analyses. The objective of this paper is to describe the basis of the chosen pediatric dose recommended for the label. Pharmacokinetic (PK) data from 90 pediatric patients receiving 7 mg/kg of body weight levofloxacin and two studies of 47 healthy adults receiving 500 and 750 mg/kg levofloxacin were used for the pharmacometric analyses. Body weight was found to be a significant covariate for levofloxacin clearance and the volume of distribution. Consistently with developmental physiology, clearance also was found to be reduced in pediatric patients under 2 years of age due to immature renal function. Different dosing regimens were simulated to match adult exposure (area under the concentration-time curve from 0 to 24 h at steady state, maximum concentration of drug in serum at steady state, and minimum concentration of drug in serum at steady state) following the approved adult dose of 500 mg once a day. The recommended dose of 8 mg/kg twice a day was found to match the exposure of the dose approved for adults in a manner that permitted confidence that this dose in children would achieve efficacy comparable to that of adults.

Issues in the reconstruction of environmental doses on the basis of thermoluminescence measurements in the Techa riverside

NASA Technical Reports Server (NTRS)

Bougrov, N. G.; Goksu, H. Y.; Haskell, E.; Degteva, M. O.; Meckbach, R.; Jacob, P.; Neta, P. I. (Principal Investigator)

1998-01-01

The potential of thermoluminescence measurements of bricks from the contaminated area of the Techa river valley, Southern Urals, Russia, for reconstructing external exposures of affected population groups has been studied. Thermoluminescence dating of background samples was used to evaluate the age of old buildings available on the river banks. The anthropogenic gamma dose accrued in exposed samples is determined by subtracting the natural radiation background dose for the corresponding age from the accumulated dose measured by thermoluminescence. For a site in the upper Techa river region, where the levels of external exposures were extremely high, the depth-dose distribution in bricks and the dependence of accidental dose on the height of the sampling position were determined. For the same site, Monte Carlo simulations of radiation transport were performed for different source configurations corresponding to the situation before and after the construction of a reservoir on the river and evacuation of the population in 1956. A comparison of the results provides an understanding of the features of the measured depth-dose distributions and height dependencies in terms of the source configurations and shows that bricks from the higher sampling positions are likely to have accrued a larger fraction of anthropogenic dose from the time before the construction of the reservoir. The applicability of the thermoluminescent dosimetry method to environmental dose reconstruction in the middle Techa region, where the external exposure was relatively low, was also investigated.

High-pitch computed tomography coronary angiography-a new dose-saving algorithm: estimation of radiation exposure.

PubMed

Ketelsen, Dominik; Buchgeister, Markus; Korn, Andreas; Fenchel, Michael; Schmidt, Bernhard; Flohr, Thomas G; Thomas, Christoph; Schabel, Christoph; Tsiflikas, Ilias; Syha, Roland; Claussen, Claus D; Heuschmid, Martin

2012-01-01

Purpose. To estimate effective dose and organ equivalent doses of prospective ECG-triggered high-pitch CTCA. Materials and Methods. For dose measurements, an Alderson-Rando phantom equipped with thermoluminescent dosimeters was used. The effective dose was calculated according to ICRP 103. Exposure was performed on a second-generation dual-source scanner (SOMATOM Definition Flash, Siemens Medical Solutions, Germany). The following scan parameters were used: 320 mAs per rotation, 100 and 120 kV, pitch 3.4 for prospectively ECG-triggered high-pitch CTCA, scan range of 13.5 cm, collimation 64 × 2 × 0.6 mm with z-flying focal spot, gantry rotation time 280 ms, and simulated heart rate of 60 beats per minute. Results. Depending on the applied tube potential, the effective whole-body dose of the cardiac scan ranged from 1.1 mSv to 1.6 mSv and from 1.2 to 1.8 mSv for males and females, respectively. The radiosensitive breast tissue in the range of the primary beam caused an increased female-specific effective dose of 8.6%±0.3% compared to males. Decreasing the tube potential, a significant reduction of the effective dose of 35.8% and 36.0% can be achieved for males and females, respectively (P < 0.001). Conclusion. The radiologist and the CT technician should be aware of this new dose-saving strategy to keep the radiation exposure as low as reasonablly achievable.

TIMING OF DIESEL PARTICLE INSTILLATION AND MAGNITUDE OF DOSE INFLUENCE THE SEVERITY OF ALLERGIC AIRWAYS RESPONSES IN MICE

EPA Science Inventory

Exposure to diesel exhaust particulates (DEP) arising from the combustion of diesel fuel exacerbates asthma. Several studies have shown that particulate and allergen co-exposure leads to an exacerbation of the hallmark features of allergic airways disease relative to allergen exp...

Effects of Prenatal Exposure to a Low Dose Atrazine Metabolite Mixture on pubertal timing and prostrate Development of Male Long Evans Rats.

EPA Science Inventory

The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and d...

MODELED RESIDENTIAL CHLORPYRIFOS EXPOSURE AND DOSE TO CHILDREN VIA DERMAL SURFACE RESIDUE CONTACT AND NON-DIETARY INGESTION

EPA Science Inventory

A physically-based stochastic model has been applied to estimate residential chlorpyrifos exposure and dace to children via the non-dietary ingestion and dermal residue contact pathways. Time-location-activity data for 2825 children were sampled from national surveys to generat...

Predicting Adaptive Response to Fadrozole Exposure: Computational Model of the Fathead Minnow Hypothalamic-Pituitary-Gonadal Axis

EPA Science Inventory

Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (...

Occupational Radiation Exposure During Endovascular Aortic Repair

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sailer, Anna M., E-mail: anni.sailer@mumc.nl; Schurink, Geert Willem H., E-mail: gwh.schurink@mumc.nl; Bol, Martine E., E-mail: m.bol@maastrichtuniversity.nl

PurposeThe aim of the study was to evaluate the radiation exposure to operating room personnel and to assess determinants for high personal doses during endovascular aortic repair.Materials and MethodsOccupational radiation exposure was prospectively evaluated during 22 infra-renal aortic repair procedures (EVAR), 11 thoracic aortic repair procedures (TEVAR), and 11 fenestrated or branched aortic repair procedures (FEVAR). Real-time over-lead dosimeters attached to the left breast pocket measured personal doses for the first operators (FO) and second operators (SO), radiology technicians (RT), scrub nurses (SN), anesthesiologists (AN), and non-sterile nurses (NSN). Besides protective apron and thyroid collar, no additional radiation shielding wasmore » used. Procedural dose area product (DAP), iodinated contrast volume, fluoroscopy time, patient’s body weight, and C-arm angulation were documented.ResultsAverage procedural FO dose was significantly higher during FEVAR (0.34 ± 0.28 mSv) compared to EVAR (0.11 ± 0.21 mSv) and TEVAR (0.06 ± 0.05 mSv; p = 0.003). Average personnel doses were 0.17 ± 0.21 mSv (FO), 0.042 ± 0.045 mSv (SO), 0.019 ± 0.042 mSv (RT), 0.017 ± 0.031 mSv (SN), 0.006 ± 0.007 mSv (AN), and 0.004 ± 0.009 mSv (NSN). SO and AN doses were strongly correlated with FO dose (p = 0.003 and p < 0.001). There was a significant correlation between FO dose and procedural DAP (R = 0.69, p < 0.001), iodinated contrast volume (R = 0.67, p < 0.001) and left-anterior C-arm projections >60° (p = 0.02), and a weak correlation with fluoroscopy time (R = 0.40, p = 0.049).ConclusionAverage FO dose was a factor four higher than SO dose. Predictors for high personal doses are procedural DAP, iodinated contrast volume, and left-anterior C-arm projections greater than 60°.« less

Dose- and time-dependent gene expression alterations in prostate and colon cancer cells after in vitro exposure to carbon ion and X-irradiation

PubMed Central

Suetens, Annelies; Moreels, Marjan; Quintens, Roel; Soors, Els; Buset, Jasmine; Chiriotti, Sabina; Tabury, Kevin; Gregoire, Vincent; Baatout, Sarah

2015-01-01

Hadrontherapy is an advanced form of radiotherapy that uses beams of charged particles (such as protons and carbon ions). Compared with conventional radiotherapy, the main advantages of carbon ion therapy are the precise absorbed dose localization, along with an increased relative biological effectiveness (RBE). This high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. Currently, hadrontherapy is being used for the treatment of specific types of cancer. Previous in vitro studies have shown that, under certain circumstances, exposure to charged particles may inhibit cell motility and migration. In the present study, we investigated the expression of four motility-related genes in prostate (PC3) and colon (Caco-2) cancer cell lines after exposure to different radiation types. Cells were irradiated with various absorbed doses (0, 0.5 and 2 Gy) of accelerated 13C-ions at the GANIL facility (Caen, France) or with X-rays. Clonogenic assays were performed to determine the RBE. RT-qPCR analysis showed dose- and time-dependent changes in the expression of CCDC88A, FN1, MYH9 and ROCK1 in both cell lines. However, whereas in PC3 cells the response to carbon ion irradiation was enhanced compared with X-irradiation, the effect was the opposite in Caco-2 cells, indicating cell-type–specific responses to the different radiation types. PMID:25190155

Sphinganine to sphingosine ratio and predictive biochemical markers of fumonisin B1 exposure in ducks.

PubMed

Tran, S T; Bailly, J D; Tardieu, D; Durand, S; Benard, G; Guerre, P

2003-07-25

The kinetics of free sphinganine (Sa), sphinganine to sphingosine ratio (Sa/So), proteins, cholesterol, alanine aminotransferase (ALAT) and lactate dehydrogenase (LDH) were investigated in the course of fumonisin B1 (FB1) exposure in ducks (20 growing males divided into four groups of 5 receiving, respectively, a daily dose of 0, 5, 15 or 45 mg/kg FB1 via oral administration over 12 days). Descriptive statistics of these parameters were also studied in a large number of ducks not exposed to mycotoxins and free of known pathology. Although the toxin at the end of the treatment affected all the parameters investigated, only 2 days of treatment appeared necessary to increase free Sa concentrations in serum, whereas 6 days were necessary to detect a significant effect on Sa/So ratio. Significant differences between control and treated ducks were observed after 4 days of treatment for ALAT and LDH and after 6 and 8 days for cholesterol and proteins concentrations. The minimum doses of FB1 required to determine an effect were assessed using three different methods. This approach reveals that FB1 has greater effects when it is ingested at a low dose for a long time than when ingested at a high dose for a short time. Although the minimum toxic dose of FB1 in ducks remains to be determined, this result must be considered in the context of chronic exposure to the toxin, not only in avian populations.

Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results.

PubMed

Hesterberg, T W; Axten, C; McConnell, E E; Oberdörster, G; Everitt, J; Miiller, W C; Chevalier, J; Chase, G R; Thevenaz, P

1997-09-01

The effects of chronic inhalation of glass fibers and amosite asbestos are currently under study in hamsters. The study includes 18 months of inhalation exposure followed by lifetime recovery. Syrian golden hamsters are exposed, nose only, for 6 hr/day, 5 day/week to size-selected test fibers: MMVF10a (Schuller 901 insulation glass); MMVF33 (Schuller 475 durable glass); amosite asbestos (three doses); or to filtered air (controls). Here we report interim results on airborne fiber characterization, lung fiber burden, and pathology (preliminary) through 12 months. Aerosolized test fibers averaged 15 to 20 microns in length and 0.5 to 1 micron in diameter. Target aerosol concentrations of World Health Organization (WHO) fibers (longer than 5 microns) were 250 fibers/cc for MMVF10a and MMVF33, and 25, 125, or 250 fibers/cc for amosite. WHO fiber lung burdens showed time-dependent and (for amosite) dose-dependent increases. After a 12-month exposure, lung burdens of fibers longer than 20 microns were greatest with amosite high and mid doses, similar for low-dose amosite and MMVF33, and smaller for MMVF10a. Biological responses of animals exposed for 12 months to MMVF10a were limited to nonspecific pulmonary inflammation. However, exposures to MMVF33 and each of three doses of amosite were associated with lung fibrosis and possible mesotheliomas (1 with MMVF33 and 2, 3, and 1 with amosite low, mid, and high doses, respectively). Pulmonary and pleural changes associated with amosite were qualitatively and quantitatively more severe than those associated with MMVF33. As of the 12-month time point, this study demonstrates that two different fiber glass compositions with similar fiber dimensions but different durabilities can have distinctly different effects on the hamster lung and pleura after inhalation exposure. (Preliminary tumor data through 18 months of exposure and 6 weeks of postexposure recovery became available as this manuscript went to press: No tumors were observed in the control or MMVF10a groups, and no additional tumors were observed in the MMVF33 group; however, a number of additional mesotheliomas were observed in the amosite groups.

Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results.

PubMed Central

Hesterberg, T W; Axten, C; McConnell, E E; Oberdörster, G; Everitt, J; Miiller, W C; Chevalier, J; Chase, G R; Thevenaz, P

1997-01-01

The effects of chronic inhalation of glass fibers and amosite asbestos are currently under study in hamsters. The study includes 18 months of inhalation exposure followed by lifetime recovery. Syrian golden hamsters are exposed, nose only, for 6 hr/day, 5 day/week to size-selected test fibers: MMVF10a (Schuller 901 insulation glass); MMVF33 (Schuller 475 durable glass); amosite asbestos (three doses); or to filtered air (controls). Here we report interim results on airborne fiber characterization, lung fiber burden, and pathology (preliminary) through 12 months. Aerosolized test fibers averaged 15 to 20 microns in length and 0.5 to 1 micron in diameter. Target aerosol concentrations of World Health Organization (WHO) fibers (longer than 5 microns) were 250 fibers/cc for MMVF10a and MMVF33, and 25, 125, or 250 fibers/cc for amosite. WHO fiber lung burdens showed time-dependent and (for amosite) dose-dependent increases. After a 12-month exposure, lung burdens of fibers longer than 20 microns were greatest with amosite high and mid doses, similar for low-dose amosite and MMVF33, and smaller for MMVF10a. Biological responses of animals exposed for 12 months to MMVF10a were limited to nonspecific pulmonary inflammation. However, exposures to MMVF33 and each of three doses of amosite were associated with lung fibrosis and possible mesotheliomas (1 with MMVF33 and 2, 3, and 1 with amosite low, mid, and high doses, respectively). Pulmonary and pleural changes associated with amosite were qualitatively and quantitatively more severe than those associated with MMVF33. As of the 12-month time point, this study demonstrates that two different fiber glass compositions with similar fiber dimensions but different durabilities can have distinctly different effects on the hamster lung and pleura after inhalation exposure. (Preliminary tumor data through 18 months of exposure and 6 weeks of postexposure recovery became available as this manuscript went to press: No tumors were observed in the control or MMVF10a groups, and no additional tumors were observed in the MMVF33 group; however, a number of additional mesotheliomas were observed in the amosite groups. PMID:9400728

A non-linear pharmacokinetic-pharmacodynamic relationship of metformin in healthy volunteers: An open-label, parallel group, randomized clinical study.

PubMed

Chung, Hyewon; Oh, Jaeseong; Yoon, Seo Hyun; Yu, Kyung-Sang; Cho, Joo-Youn; Chung, Jae-Yong

2018-01-01

The aim of this study was to explore the pharmacokinetic-pharmacodynamic (PK-PD) relationship of metformin on glucose levels after the administration of 250 mg and 1000 mg of metformin in healthy volunteers. A total of 20 healthy male volunteers were randomized to receive two doses of either a low dose (375 mg followed by 250 mg) or a high dose (1000 mg followed by 1000 mg) of metformin at 12-h intervals. The pharmacodynamics of metformin was assessed using oral glucose tolerance tests before and after metformin administration. The PK parameters after the second dose were evaluated through noncompartmental analyses. Four single nucleotide polymorphisms in MATE1, MATE2-K, and OCT2 were genotyped, and their effects on PK characteristics were additionally evaluated. The plasma exposure of metformin increased as the metformin dose increased. The mean values for the area under the concentration-time curve from dosing to 12 hours post-dose (AUC0-12h) were 3160.4 and 8808.2 h·μg/L for the low- and high-dose groups, respectively. Non-linear relationships were found between the glucose-lowering effect and PK parameters with a significant inverse trend at high metformin exposure. The PK parameters were comparable among subjects with the genetic polymorphisms. This study showed a non-linear PK-PD relationship on plasma glucose levels after the administration of metformin. The inverse relationship between systemic exposure and the glucose-lowering effect at a high exposure indicates a possible role for the intestines as an action site for metformin. ClinicalTrials.gov NCT02712619.

A new form of the calibration curve in radiochromic dosimetry. Properties and results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamponi, Matteo, E-mail: mtamponi@aslsassari.it; B

Purpose: This work describes a new form of the calibration curve for radiochromic dosimetry that depends on one fit parameter. Some results are reported to show that the new curve performs as well as those previously used and, more importantly, significantly reduces the dependence on the lot of films, the film orientation on the scanner, and the time after exposure. Methods: The form of the response curve makes use of the net optical densities ratio against the dose and has been studied by means of the Beer–Lambert law and a simple modeling of the film. The new calibration curve hasmore » been applied to EBT3 films exposed at 6 and 15 MV energy beams of linear accelerators and read-out in transmission mode by means of a flatbed color scanner. Its performance has been compared to that of two established forms of the calibration curve, which use the optical density and the net optical density against the dose. Four series of measurements with four lots of EBT3 films were used to evaluate the precision, accuracy, and dependence on the time after exposure, orientation on the scanner and lot of films. Results: The new calibration curve is roughly subject to the same dose uncertainty, about 2% (1 standard deviation), and has the same accuracy, about 1.5% (dose values between 50 and 450 cGy), as the other calibration curves when films of the same lot are used. Moreover, the new calibration curve, albeit obtained from only one lot of film, shows a good agreement with experimental data from all other lots of EBT3 films used, with an accuracy of about 2% and a relative dose precision of 2.4% (1 standard deviation). The agreement also holds for changes of the film orientation and of the time after exposure. Conclusions: The dose accuracy of this new form of the calibration curve is always equal to or better than those obtained from the two types of curves previously used. The use of the net optical densities ratio considerably reduces the dependence on the lot of films, the landscape/portrait orientation, and the time after exposure. This form of the calibration curve could become even more useful with new optical digital devices using monochromatic light.« less

A new form of the calibration curve in radiochromic dosimetry. Properties and results.

PubMed

Tamponi, Matteo; Bona, Rossana; Poggiu, Angela; Marini, Piergiorgio

2016-07-01

This work describes a new form of the calibration curve for radiochromic dosimetry that depends on one fit parameter. Some results are reported to show that the new curve performs as well as those previously used and, more importantly, significantly reduces the dependence on the lot of films, the film orientation on the scanner, and the time after exposure. The form of the response curve makes use of the net optical densities ratio against the dose and has been studied by means of the Beer-Lambert law and a simple modeling of the film. The new calibration curve has been applied to EBT3 films exposed at 6 and 15 MV energy beams of linear accelerators and read-out in transmission mode by means of a flatbed color scanner. Its performance has been compared to that of two established forms of the calibration curve, which use the optical density and the net optical density against the dose. Four series of measurements with four lots of EBT3 films were used to evaluate the precision, accuracy, and dependence on the time after exposure, orientation on the scanner and lot of films. The new calibration curve is roughly subject to the same dose uncertainty, about 2% (1 standard deviation), and has the same accuracy, about 1.5% (dose values between 50 and 450 cGy), as the other calibration curves when films of the same lot are used. Moreover, the new calibration curve, albeit obtained from only one lot of film, shows a good agreement with experimental data from all other lots of EBT3 films used, with an accuracy of about 2% and a relative dose precision of 2.4% (1 standard deviation). The agreement also holds for changes of the film orientation and of the time after exposure. The dose accuracy of this new form of the calibration curve is always equal to or better than those obtained from the two types of curves previously used. The use of the net optical densities ratio considerably reduces the dependence on the lot of films, the landscape/portrait orientation, and the time after exposure. This form of the calibration curve could become even more useful with new optical digital devices using monochromatic light.

POPULATION EXPOSURE AND DOSE MODEL FOR AIR TOXICS: A BENZENE CASE STUDY

EPA Science Inventory

The EPA's National Exposure Research Laboratory (NERL) is developing a human exposure and dose model called the Stochastic Human Exposure and Dose Simulation model for Air Toxics (SHEDS-AirToxics) to characterize population exposure to air toxics in support of the National Air ...

Space radiation risks to the central nervous system

NASA Astrophysics Data System (ADS)

Cucinotta, Francis A.; Alp, Murat; Sulzman, Frank M.; Wang, Minli

2014-07-01

Central nervous system (CNS) risks which include during space missions and lifetime risks due to space radiation exposure are of concern for long-term exploration missions to Mars or other destinations. Possible CNS risks during a mission are altered cognitive function, including detriments in short-term memory, reduced motor function, and behavioral changes, which may affect performance and human health. The late CNS risks are possible neurological disorders such as premature aging, and Alzheimer's disease (AD) or other dementia. Radiation safety requirements are intended to prevent all clinically significant acute risks. However the definition of clinically significant CNS risks and their dependences on dose, dose-rate and radiation quality is poorly understood at this time. For late CNS effects such as increased risk of AD, the occurrence of the disease is fatal with mean time from diagnosis of early stage AD to death about 8 years. Therefore if AD risk or other late CNS risks from space radiation occur at mission relevant doses, they would naturally be included in the overall acceptable risk of exposure induced death (REID) probability for space missions. Important progress has been made in understanding CNS risks due to space radiation exposure, however in general the doses used in experimental studies have been much higher than the annual galactic cosmic ray (GCR) dose (∼0.1 Gy/y at solar maximum and ∼0.2 Gy/y at solar minimum with less than 50% from HZE particles). In this report we summarize recent space radiobiology studies of CNS effects from particle accelerators simulating space radiation using experimental models, and make a critical assessment of their relevance relative to doses and dose-rates to be incurred on a Mars mission. Prospects for understanding dose, dose-rate and radiation quality dependencies of CNS effects and extrapolation to human risk assessments are described.

PRELIMINARY REPORT: EFFECTS OF IRRADIATION AND THERMAL EXPOSURE ON ELASTOMERIC SEALS FOR CASK TRANSPORTATION AND STORAGE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verst, C.; Skidmore, E.; Daugherty, W.

2014-05-30

A testing and analysis approach to predict the sealing behavior of elastomeric seal materials in dry storage casks and evaluate their ability to maintain a seal under thermal and radiation exposure conditions of extended storage and beyond was developed, and initial tests have been conducted. The initial tests evaluate the aging response of EPDM elastomer O-ring seals. The thermal and radiation exposure conditions of the CASTOR® V/21 casks were selected for testing as this cask design is of interest due to its widespread use, and close proximity of the seals to the fuel compared to other cask designs leading tomore » a relatively high temperature and dose under storage conditions. A novel test fixture was developed to enable compression stress relaxation measurements for the seal material at the thermal and radiation exposure conditions. A loss of compression stress of 90% is suggested as the threshold at which sealing ability of an elastomeric seal would be lost. Previous studies have shown this value to be conservative to actual leakage failure for most aging conditions. These initial results indicate that the seal would be expected to retain sealing ability throughout extended storage at the cask design conditions, though longer exposure times are needed to validate this assumption. The high constant dose rate used in the testing is not prototypic of the decreasingly low dose rate that would occur under extended storage. The primary degradation mechanism of oxidation of polymeric compounds is highly dependent on temperature and time of exposure, and with radiation expected to exacerbate the oxidation.« less

Biological Response to SPE Exposures

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Cucinotta, F. A.; Kim, M.; Shinn, J. L.; Jones, T. D.; Chang, C. K.

2004-01-01

It has long been recognized that a single solar particle event (SPE) can produce, over a short period of time, exposures on the order of LD50 for humans under normal physiological conditions. It is further recognized that recovery from injury over the period of exposure would greatly increase the chances of survival (dose rate effects) although such effects were left unquantified. In the present report we use the bioresponse model derived from a broad range of animal and human exposure data for evaluation of troop readiness in tactical nuclear warfare to evaluate the biological risk posed by the solar event of 4 August 1972. The astronaut blood forming organ (BFO) exposure in deep space would have been 2.2 Sv (1.6 Gy) in a space suit, 1.8 Sv (1.3 Gy) in an aluminum pressure vessel, and 0.7 Sv (0.5 Gy) in an equipment room compared to an X-ray mortality threshold of 1.5 Gy (assuming high dose rate). We find BFO dose rate effectiveness factors for this SPE on the order of 3 to 4, greatly reducing the mortality risks for this event. There is an approximate 3 percent chance that an even larger event may occur for which exposures could be 2-4 times higher. Assured survival of the astronaut requires added shelter shielding and a warning system for this event. The required mass of the shelter shield can be greatly reduced by using hydrogenous materials such as polymers, water, food, and other biological materials in its construction. Limitations of the current bioresponse model arise from the exposures taking place in the microgravity environment wherein the immune system is already challenged and the effective mortality threshold may be reduced by a factor of two. Such microgravity effects could greatly affect astronaut risks.

Toxicokinetics of the flame retardant hexabromocyclododecane alpha: effect of dose, timing, route, repeated exposure, and metabolism.

PubMed

Szabo, David Taylor; Diliberto, Janet J; Hakk, Heldur; Huwe, Janice K; Birnbaum, Linda S

2011-06-01

Alpha-hexabromocyclododecane (α-HBCD) is an emerging persistent organic pollutant present in the hexabromocyclododecane (HBCD) commercial mixture. HBCD is used as an additive flame retardant in a wide variety of household consumer products. Three main stereoisomers, alpha (α), beta (β), and gamma (γ), comprise roughly 10, 10, and 80% of the mixture, respectively. Despite its small contribution to HBCD global production and usage, α-HBCD is the major stereoisomer found in wildlife and human tissues including breast milk and blood in North America, European Union, and Asia. No mammalian or human data are currently available regarding the toxicokinetics of α-HBCD. This study was conducted in an effort to fully characterize the absorption, distribution, metabolism, and elimination of α-HBCD following a single and repeated exposure with respect to dose, time, and route of administration in female C57BL/6 mice. Results indicate that ∼90% of the administered dose (3 mg/kg) was absorbed after oral exposure. Disposition was (1) dictated by lipophilicity, as adipose, liver, muscle, and skin were major depots and (2) was dose dependent with nonlinear accumulation at higher doses. Elimination, both whole-body and from individual tissues, was biphasic. α-HBCD-derived radioactivity was excreted in the feces as parent and metabolites, whereas urine only contained metabolites. Presence of polar metabolites in the blood and urine were a major factor in determining the rapid initial whole-body half-life after a single oral exposure. Initial half-lives were ∼1-3 days and much longer terminal half-lives of 17 days were observed, suggesting the potential for α-HBCD bioaccumulation. A 10-day repeated study supports α-HBCD bioaccumulation potential. Stereoisomerization previously observed after exposure to γ-HBCD was not seen after exposure of α-HBCD. The toxicokinetic behavior reported here has important implications for the extrapolation of toxicological studies of the commercial HBCD mixture to the assessment of risk of α-HBCD which is the major stereoisomer found in wildlife and people.

The effects of proton exposure on neurochemistry and behavior

NASA Technical Reports Server (NTRS)

Shukitt-Hale, B.; Szprengiel, A.; Pluhar, J.; Rabin, B. M.; Joseph, J. A.

2004-01-01

Future space missions will involve long-term travel beyond the magnetic field of the Earth, where astronauts will be exposed to radiation hazards such as those that arise from galactic cosmic rays. Galactic cosmic rays are composed of protons, alpha particles, and particles of high energy and charge (HZE particles). Research by our group has shown that exposure to HZE particles, primarily 600 MeV/n and 1 GeV/n 56Fe, can produce significant alterations in brain neurochemistry and behavior. However, given that protons can make up a significant portion of the radiation spectrum, it is important to study their effects on neural functioning and on related performance. Therefore, these studies examined the effects of exposure to proton irradiation on neurochemical and behavioral endpoints, including dopaminergic functioning, amphetamine-induced conditioned taste aversion learning, and spatial learning and memory as measured by the Morris water maze. Male Sprague-Dawley rats received a dose of 0, 1.5, 3.0 or 4.0 Gy of 250 MeV protons at Loma Linda University and were tested in the different behavioral tests at various times following exposure. Results showed that there was no effect of proton irradiation at any dose on any of the endpoints measured. Therefore, there is a contrast between the insignificant effects of high dose proton exposure and the dramatic effectiveness of low dose (<0.1 Gy) exposures to 56Fe particles on both neurochemical and behavioral endpoints. Published by Elsevier Ltd on behalf of COSPAR.

Pharmacodynamics of levofloxacin in a murine pneumonia model of Pseudomonas aeruginosa infection: determination of epithelial lining fluid targets.

PubMed

Louie, Arnold; Fregeau, Christine; Liu, Weiguo; Kulawy, Robert; Drusano, G L

2009-08-01

The dose choice for Pseudomonas aeruginosa remains a matter of debate. The actual exposure targets required for multilog killing of organisms at the primary infection site have not been delineated. We studied Pseudomonas aeruginosa PAO1 using a murine model of pneumonia. We employed a large mathematical model to fit all the concentration-time data in plasma and epithelial lining fluid (ELF) as well as colony counts in lung simultaneously for all drug doses. Penetration into ELF was calculated to be approximately 77.7%, as indexed to the ratio of the area under the concentration-time curve for ELF (AUC(ELF)) to the AUC(plasma). We determined the ELF concentration-time profile required to drive a stasis response as well as 1-, 2-, or 3-log(10)(CFU/g) kill. AUC/MIC ratios of 12.4, 31.2, 62.8, and 127.6 were required to drive these bacterial responses. Emergence of resistance was seen only at the two lowest doses (three of five animals at 50 mg/kg [body weight] and one of five animals at 100 mg/kg). The low exposure targets were likely driven by a low mutational frequency to resistance. Bridging to humans was performed using Monte Carlo simulation. With a 750-mg levofloxacin dose, target attainment rates fell below 90% at 4 mg/liter, 1 mg/liter, and 0.5 mg/liter for 1-, 2-, and 3-log kills, respectively. Given the low exposure targets seen with this strain, we conclude that levofloxacin at a 750-mg dose is not adequate for serious Pseudomonas aeruginosa pneumonia as a single agent. More isolates need to be studied to make these observations more robust.

Pharmacodynamics of Levofloxacin in a Murine Pneumonia Model of Pseudomonas aeruginosa Infection: Determination of Epithelial Lining Fluid Targets▿

PubMed Central

Louie, Arnold; Fregeau, Christine; Liu, Weiguo; Kulawy, Robert; Drusano, G. L.

2009-01-01

The dose choice for Pseudomonas aeruginosa remains a matter of debate. The actual exposure targets required for multilog killing of organisms at the primary infection site have not been delineated. We studied Pseudomonas aeruginosa PAO1 using a murine model of pneumonia. We employed a large mathematical model to fit all the concentration-time data in plasma and epithelial lining fluid (ELF) as well as colony counts in lung simultaneously for all drug doses. Penetration into ELF was calculated to be approximately 77.7%, as indexed to the ratio of the area under the concentration-time curve for ELF (AUCELF) to the AUCplasma. We determined the ELF concentration-time profile required to drive a stasis response as well as 1-, 2-, or 3-log10(CFU/g) kill. AUC/MIC ratios of 12.4, 31.2, 62.8, and 127.6 were required to drive these bacterial responses. Emergence of resistance was seen only at the two lowest doses (three of five animals at 50 mg/kg [body weight] and one of five animals at 100 mg/kg). The low exposure targets were likely driven by a low mutational frequency to resistance. Bridging to humans was performed using Monte Carlo simulation. With a 750-mg levofloxacin dose, target attainment rates fell below 90% at 4 mg/liter, 1 mg/liter, and 0.5 mg/liter for 1-, 2-, and 3-log kills, respectively. Given the low exposure targets seen with this strain, we conclude that levofloxacin at a 750-mg dose is not adequate for serious Pseudomonas aeruginosa pneumonia as a single agent. More isolates need to be studied to make these observations more robust. PMID:19364849

Development of a Non-Invasive Biomonitoring Approach to Determine Exposure to the Organophosphorus Insecticide Chlorpyrifos in Rat Saliva

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timchalk, Chuck; Campbell, James A.; Liu, Guodong

2007-03-01

Abstract Non-invasive biomonitoring approaches are being developed using reliable portable analytical systems to quantify dosimetry utilizing readily obtainable body fluids, such as saliva. In the current study, rats were given single oral gavage doses (1, 10 or 50 mg/kg) of the insecticide chlorpyrifos (CPF), saliva and blood were collected from groups of animals (4/time-point) at 3, 6, and 12 hr post-dosing, and the samples were analyzed for the CPF metabolite trichlorpyridinol (TCP). Trichlorpyridinol was detected in both blood and saliva at all doses and the TCP concentration in blood exceeded saliva, although the kinetics in blood and saliva were comparable.more » A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF incorporated a compartment model to describe the time-course of TCP in blood and saliva. The model adequately simulated the experimental results over the dose ranges evaluated. A rapid and sensitive sequential injection (SI) electrochemical immunoassay was developed to monitor TCP, and the reported detection limit for TCP in water was 6 ng/L. Computer model simulation in the range of the Allowable Daily Intake (ADI) or Reference Dose (RfD) for CPF (0.01-0.003 mg/kg/day) suggest that the electrochemical immunoassay had adequate sensitivity to detect and quantify TCP in saliva at these low exposure levels. To validate this approach further studies are needed to more fully understand the pharmacokinetics of CPF and TCP excretion in saliva. The utilization of saliva as a biomonitoring matrix, coupled to real-time quantitation and PBPK/PD modeling represents a novel approach with broad application for evaluating both occupational and environmental exposures to insecticides.« less

Pharmacokinetic interactions of efavirenz and voriconazole in healthy volunteers

PubMed Central

Damle, Bharat; LaBadie, Robert; Crownover, Penelope; Glue, Paul

2008-01-01

AIMS Co-administration of standard-dose voriconazole and efavirenz results in a substantial decrease in voriconazole levels, while concurrently increasing efavirenz levels. Hence, concomitant use of standard doses of these drugs was initially contraindicated. This study assessed different dose combinations of efavirenz and voriconazole, with the goal of attaining a dose combination that provides systemic exposures similar to standard-dose monotherapy with each drug. METHODS This was an open-label, four-treatment, multiple-dose, fixed-sequence study in 16 healthy males. Steady-state pharmacokinetics were assessed following two test treatments (voriconazole 300 mg q12 h + efavirenz 300 mg q24 h and voriconazole 400 mg q12 h + efavirenz 300 mg q24 h) and compared with standard-dose monotherapy (voriconazole 200 mg q12 h or efavirenz 600 mg q24 h). RESULTS Dose adjustment to voriconazole 300 mg q12 h with efavirenz 300 mg q24 h decreased voriconazole area under the concentration–time curve (AUCτ) and maximum concentration (Cmax), with changes of −55% [90% confidence interval (CI) −62, −45] and −36% (90% CI −49, −21), respectively, when compared with monotherapy. Voriconazole 400 mg q12 h plus efavirenz 300 mg q24 h decreased voriconazole AUCτ (−7%; 90% CI −23, 13) and increased Cmax (23%; 90% CI −1, 53), while increasing efavirenz AUCτ (17%; 90% CI 6, 29) and not changing Cmax when compared with the respective monotherapy regimens. No serious adverse events were observed with voriconazole plus efavirenz. CONCLUSIONS When co-administered, voriconazole dose should be increased to 400 mg q12 h and efavirenz dose decreased to 300 mg q24 h in order to provide systemic exposures similar to standard-dose monotherapy. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Efavirenz 400 mg q24 h reduces exposure to voriconazole 200 mg q12 h when the two drugs are co-administered.Furthermore, voriconazole increases the systemic exposure of efavirenz.Co-administration was therefore initially contraindicated. WHAT THIS STUDY ADDS The doses of efavirenz and voriconazole can be adjusted to provide adequate exposure to both drugs when the two are co-administered, without compromising safety.Appropriate adjustment of doses for both drugs may thus represent an alternative to a mere contraindication. PMID:18294336

Cytogenetic Reconstruction of Gamma-Ray Doses Delivered to Atomic Bomb Survivors: Dealing with Wide Distributions of Photon Energies and Contributions from Hematopoietic Stem/Progenitor Cells.

PubMed

Nakamura, Nori; Hirai, Yuko; Kodama, Yoshiaki; Hamasaki, Kanya; Cullings, Harry M; Cordova, Kismet A; Awa, Akio

2017-10-01

Retrospective estimation of the doses received by atomic bomb (A-bomb) survivors by cytogenetic methods has been hindered by two factors: One is that the photon energies released from the bomb were widely distributed, and since the aberration yield varies depending on the energy, the use of monoenergetic 60 Co gamma radiation to construct a calibration curve may bias the estimate. The second problem is the increasing proportion of newly formed lymphocytes entering into the lymphocyte pool with increasing time intervals since the exposures. These new cells are derived from irradiated precursor/stem cells whose radiosensitivity may differ from that of blood lymphocytes. To overcome these problems, radiation doses to tooth enamel were estimated using the electron spin resonance (ESR; or EPR, electron paramagnetic resonance) method and compared with the cytogenetically estimated doses from the same survivors. The ESR method is only weakly dependent on the photon energy and independent of the years elapsed since an exposure. Both ESR and cytogenetic doses were estimated from 107 survivors. The latter estimates were made by assuming that although a part of the cells examined could be lymphoid stem or precursor cells at the time of exposure, all the cells had the same radiosensitivity as blood lymphocytes, and that the A-bomb gamma-ray spectrum was the same as that of the 60 Co gamma rays. Subsequently, ESR and cytogenetic endpoints were used to estimate the kerma doses using individual DS02R1 information on shielding conditions. The results showed that the two sets of kerma doses were in close agreement, indicating that perhaps no correction is needed in estimating atomic bomb gamma-ray doses from the cytogenetically estimated 60 Co gamma-ray equivalent doses. The present results will make it possible to directly compare cytogenetic doses with the physically estimated doses of the survivors, which would pave the way for testing whether or not there are any systematic trends or factors affecting physically estimated doses.

The effect of single and repeated UVB radiation on rabbit cornea.

PubMed

Fris, Miroslav; Tessem, May-Britt; Cejková, Jitka; Midelfart, Anna

2006-12-01

Cumulative effect of ultraviolet radiation (UVR) is an important aspect of UV corneal damage. The purpose of this study was to apply high resolution magic angle spinning proton nuclear magnetic resonance (HR-MAS 1H NMR) spectroscopy to evaluate the effect of single and repeated UV radiation exposure of the same overall dose on the rabbit cornea. Corneal surfaces of 24 normal rabbit eyes were examined for the effects of UVB exposure (312 nm). In the first group (UVB1), animals were irradiated with a single dose (3.12 J/cm2; 21 min) of UVB radiation. The animals in the second group (UVB2) were irradiated three times for 7 min every other day (dose of 1.04 J/cm2; days 1, 3, 5) to give the same overall dose (3.12 J/cm2). The third group served as an untreated control group. One day after the last irradiation, the animals were sacrificed, and the corneas were removed and frozen. HR-MAS 1H NMR spectra from intact corneas were obtained. Special grouping patterns among the tissue samples and the relative percentage changes in particular metabolite concentrations were evaluated using modern statistical methods (multivariate analysis, one-way ANOVA). The metabolic profile of both groups of UVB-irradiated samples was significantly different from the control corneas. Substantial decreases in taurine, hypo-taurine and choline-derivatives concentrations and substantial elevation in glucose and betaine levels were observed following the UVR exposure. There was no significant difference between the effect of a single and repeated UVB irradiation of the same overall dose. For the first time, the effects of single and repeated UVR doses on the metabolic profile of the rabbit cornea were analysed and compared. The combination of HR-MAS 1H NMR spectroscopy and modern statistical methods (multivariate analysis, one-way ANOVA) proved suitable to assess the overall view of the metabolic alterations in the rabbit corneal tissue following UVB radiation exposure.

1H NMR spectroscopic analysis detects metabolic disturbances in rat urine on acute exposure to heavy metal tungsten alloy based metals salt.

PubMed

Tyagi, Ritu; Rana, Poonam; Gupta, Mamta; Bhatnagar, Deepak; Srivastava, Shatakshi; Roy, Raja; Khushu, Subash

2014-03-25

Heavy metal tungsten alloys (HMTAs) have been found to be safer alternatives for making military munitions. Recently, some studies demonstrating the toxic potential of HMTAs have raised concern over the safety issues, and further propose that HMTAs exposure may lead to physiological disturbances as well. To look for the systemic effect of acute toxicity of HMTA based metals salt, (1)H nuclear magnetic resonance ((1)H NMR) spectroscopic profiling of rat urine was carried out. Male Sprague Dawley rats were administered (intraperitoneal) low and high dose of mixture of HMTA based metals salt and NMR spectroscopy was carried out in urine samples collected at 8, 24, 72 and 120 h post dosing (p.d.). Serum biochemical parameters and liver histopathology were also conducted. The (1)H NMR spectra were analysed using multivariate analysis techniques to show the time- and dose-dependent biochemical variations in post HMTA based metals salt exposure. Urine metabolomic analysis showed changes associated with energy metabolism, amino acids, N-methyl nicotinamide, membrane and gut flora metabolites. Multivariate analysis showed maximum variation with best classification of control and treated groups at 24h p.d. At the end of the study, for the low dose group most of the changes at metabolite level reverted to control except for the energy metabolites; whereas, in the high dose group some of the changes still persisted. The observations were well correlated with histopathological and serum biochemical parameters. Further, metabolic pathway analysis clarified that amongst all the metabolic pathways analysed, tricarboxylic acid cycle was most affected at all the time points indicating a switchover in energy metabolism from aerobic to anaerobic. These results suggest that exposure of rats to acute doses of HMTA based metals salt disrupts physiological metabolism with moderate injury to the liver, which might indirectly result from heavy metals induced oxidative stress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Further Characterization of the Mitigation of Radiation Lethality by Protective Wounding

PubMed Central

Dynlacht, Joseph R.; Garrett, Joy; Joel, Rebecca; Lane, Katharina; Mendonca, Marc S.; Orschell, Christie M.

2017-01-01

There continues to be a major effort in the United States to develop mitigators for the treatment of mass casualties that received high-intensity acute ionizing radiation exposures from the detonation of an improvised nuclear device during a radiological terrorist attack. The ideal countermeasure should be effective when administered after exposure, and over a wide range of absorbed doses. We have previously shown that the administration of a subcutaneous incision of a defined length, if administered within minutes after irradiation, protected young adult female C57BL/6 mice against radiation-induced lethality, and increased survival after total-body exposure to an LD50/30 X-ray dose from 50% to over 90%. We refer to this approach as “protective wounding”. In this article, we report on our efforts to further optimize, characterize and demonstrate the validity of the protective wounding response by comparing the response of female and male mice, varying the radiation dose, the size of the wound, and the timing of wounding with respect to administration of the radiation dose. Both male and female mice that received a subcutaneous incision after irradiation were significantly protected from radiation lethality. We observed that the extent of protection against lethality after an LD50/30 X-ray dose was independent of the size of the subcutaneous cut, and that a 3 mm subcutaneous incision is effective at enhancing the survival of mice exposed to a broad range of radiation doses (LD15–LD100). Over the range of 6.2–6.7 Gy, the increase in survival observed in mice that received an incision was associated with an enhanced recovery of hematopoiesis. The enhanced rate of recovery of hematopoiesis was preceded by an increase in the production of a select group of cytokines. Thus, a thorough knowledge of the timing of the cytokine cascade after wounding could aid in the development of novel pharmacological radiation countermeasures that can be administered several days after the actual radiation exposure. PMID:28437188

Effects of maternal and lactational exposure to 2-hydroxy-4-methoxybenzone on development and reproductive organs in male and female rat offspring

PubMed Central

Nakamura, Noriko; Inselman, Amy L.; White, Gene A.; Chang, Ching-Wei; Trbojevich, Raul A.; Sepehr, Estatira; Voris, Kristie L.; Patton, Ralph E.; Bryant, Matthew S.; Harrouk, Wafa; McIntyre, Barry; Foster, Paul M.; Hansen, Deborah K.

2015-01-01

BACKGROUND 2-hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV)-absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential. METHODS To determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1,000, 3,000, 10,000, 25,000, or 50,000 ppm HMB (7-8 per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23. RESULTS AND CONCLUSION Exposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats. PMID:25707689

Pharmacokinetics of a Single Oral Dose of the MEK1/2 Inhibitor Selumetinib in Subjects With End‐Stage Renal Disease or Varying Degrees of Hepatic Impairment Compared With Healthy Subjects

PubMed Central

Dymond, Angela W.; Martin, Paul; Huang, Yifan; Severin, Paul; Holmes, Victoria; Mariani, Gabriella; Marbury, Thomas

2016-01-01

Abstract Two phase I open‐label studies were conducted to investigate the pharmacokinetics (PK), safety, and tolerability of single oral doses of selumetinib in subjects with end‐stage renal disease (ESRD) undergoing hemodialysis and subjects with varying degrees of hepatic impairment; both studies included a matched control group comprised of healthy individuals. In the renal impairment study, subjects received single doses of selumetinib 50 mg; those with ESRD received selumetinib before and after dialysis (with a between‐treatment washout period of ≥7 days). In the hepatic impairment study, subjects received varying single doses of selumetinib (20‐50 mg) depending on liver dysfunction (mild, moderate, or severe as per Child‐Pugh classification). PK, safety, and tolerability data were collected from both studies. Overall, 24 subjects were included in the renal impairment study (ESRD, N = 12; healthy subjects, N = 12). Selumetinib exposure (AUC and Cmax) was not increased in the ESRD group vs healthy subjects. Selumetinib exposure was lower when selumetinib was dosed before vs after dialysis, although individual exposure was variable. Overall, 32 subjects were included in the hepatic impairment study (mild, moderate, and severe impairment, N = 8 per group; healthy subjects, N = 8). Generally, dose‐normalized total selumetinib exposure was increased by 25% to 59% in subjects with moderate and severe hepatic impairment compared with healthy subjects. Increasing Child‐Pugh score, decreasing serum albumin, and increasing prothrombin time correlated with increasing unbound selumetinib exposure. In both studies, selumetinib was well tolerated with no new safety concerns. These studies will inform dose adjustment considerations in patients. PMID:28019010

Long-lasting behavioral effects in neonatal mice with multiple exposures to ketamine-xylazine anesthesia

PubMed Central

Huang, Lianyan; Hayes, Scott; Yang, Guang

2016-01-01

Anesthetic agents are often administered in the neonatal period, a time of rapid brain development and synaptogenesis. Mounting evidence suggests that anesthetics can disrupt neurocognitive development, particularly in cases of multiple or prolonged anesthetic exposure. Previous studies have shown that administering multiple doses of ketamine-xylazine (KX) anesthesia to neonatal mice can induce long-term changes to synaptic plasticity in the cortex, but the effect on neurocognitive function remains unclear. In this study, we exposed neonatal mice to single dose and multiple doses of KX anesthesia in the neonatal period (postnatal days 7, 9, 11), and conducted a series of behavioral tests in young adulthood (1 month of age). Mice receiving multiple doses of KX anesthesia showed deficits in novel object recognition, sociability, preference for social novelty and contextual fear response, but no effect on auditory-cued fear response. Single dose of KX anesthesia had no effect on these behaviors except for contextual fear response. We also observed that multiple exposures to KX anesthesia were associated with decreased CaMKII phosphorylation, which is known to play a role in synapse development and long-term potentiation, likely contributing to learning impairment. PMID:27622724

Longitudinal trends of total white blood cell and differential white blood cell counts of atomic bomb survivors.

PubMed

Hsu, Wan-Ling; Tatsukawa, Yoshimi; Neriishi, Kazuo; Yamada, Michiko; Cologne, John; Fujiwara, Saeko

2010-01-01

In studying the late health effects of atomic-bomb (A-bomb) survivors, earlier findings were that white blood cell (WBC) count increased with radiation dose in cross-sectional studies. However, a persistent effect of radiation on WBC count and other risk factors has yet to be confirmed. The objectives of the present study were 1) to examine the longitudinal relationship between A-bomb radiation dose and WBC and differential WBC counts among A-bomb survivors and 2) to investigate the potential confounding risk factors (such as age at exposure and smoking status) as well as modification of the radiation dose-response. A total of 7,562 A-bomb survivors in Hiroshima and Nagasaki were included in this study from 1964-2004. A linear mixed model was applied using the repeated WBC measurements. During the study period, a secular downward trend of WBC count was observed. Radiation exposure was a significant risk factor for elevated WBC and differential WBC counts over time. A significant increase of WBC counts among survivors with high radiation dose (> 2 Gy) was detected in men exposed below the age of 20 and in women regardless of age at exposure. Effects on WBC of low dose radiation remain unclear, however. Cigarette smoking produced the most pronounced effect on WBC counts and its impact was much larger than that of radiation exposure.

Marked depression of time interval between fertilization period and hatching period following exposure to low-dose X-rays in zebrafish.

PubMed

Miyachi, Yukihisa; Kanao, Tomoko; Okamoto, Takehito

2003-10-01

In recent years there has been growing concern over the stimulating effects of very low-dose X-rays. Our laboratory had observed that zebrafish irradiated with low-dose X-rays tended to emerge earlier than sham controls. This observation led us to quantitatively examine the effects of low-dose X irradiation on a series of stages of development in the zebrafish. The embryos were fertilized simultaneously in vitro and incubated at an optimal temperature without crowding. Following exposure of the cleavage period (1.5 h after fertilization) to 0.025-Gy X-rays, the duration to hatching was slightly shorter than that of the sham controls. This tendency was increased when the X-ray exposure occurred during the blastula period (3.5 h). In these embryos, the duration to hatching decreased significantly by an average of 6 h sooner than for sham controls. No differences in duration to hatching were seen when irradiation was given during either the zygote period (45 min) or the segmentation period (12 h). On the contrary, upon exposure to 0.5-Gy X-rays during the blastula period, the duration to hatching increased significantly relative to that of sham controls. These results suggest that the radiation-induced early hatching effect is observed for low doses of X-rays.

SU-E-I-22: Dependence On Calibration Phantom and Field Area of the Conversion Factor Used to Calculate Skin Dose During Neuro-Interventional Fluoroscopic Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rana, V K; Vijayan, S; Rudin, S R

Purpose: To determine the appropriate calibration factor to use when calculating skin dose with our real-time dose-tracking system (DTS) during neuro-interventional fluoroscopic procedures by evaluating the difference in backscatter from different phantoms and as a function of entrance-skin field area. Methods: We developed a dose-tracking system to calculate and graphically display the cumulative skin-dose distribution in real time. To calibrate the DTS for neuro-interventional procedures, a phantom is needed that closely approximates the scattering properties of the head. We compared the x-ray backscatter from eight phantoms: 20-cm-thick solid water, 16-cm diameter water-filled container, 16-cm CTDI phantom, modified-ANSI head phantom, 20-cm-thickmore » PMMA, Kyoto-Kagaku PBU- 50 head, Phantom-Labs SK-150 head, and RSD RS-240T head. The phantoms were placed on the patient table with the entrance surface at 15 cm tube-side from the isocenter of a Toshiba Infinix C-arm, and the entrance-skin exposure was measured with a calibrated 6-cc PTW ionization chamber. The measurement included primary radiation, backscatter from the phantom and forward scatter from the table and pad. The variation in entrance-skin exposure was also measured as a function of the skin-entrance area for a 30x30 cm by 20-cm-thick PMMA phantom and the SK-150 head phantom using four different added beam filters. Results: The entranceskin exposure values measured for eight different phantoms differed by up to 12%, while the ratio of entrance exposure of all phantoms relative to solid water showed less than 3% variation with kVp. The change in entrance-skin exposure with entrance-skin area was found to differ for the SK-150 head compared to the 20-cm PMMA phantom and the variation with field area was dependent on the added beam filtration. Conclusion: To accurately calculate skin dose for neuro-interventional procedures with the DTS, the phantom for calibration should be carefully chosen since different phantoms can contribute different backscatter for identical exposure parameters. Research supported in part by Toshiba Medical Systems and NIH Grants R43FD0158401, R44FD0158402 and R01EB002873.« less

Does exposure to glyphosate lead to an increase in the micronuclei frequency? A systematic and meta-analytic review.

PubMed

Ghisi, Nédia de Castilhos; de Oliveira, Elton Celton; Prioli, Alberto José

2016-02-01

Glyphosate-based herbicides are among the most used pesticides worldwide. Reviews on the safety of glyphosate have been conducted by several regulatory agencies and researches centers, many times with contradictory results. This study is a systematic meta-analytical review of experimental studies on the relationship between exposure to the glyphosate (GLY) and its formulations with the formation of micronuclei (MN) to establish a quantitative estimate of the environmental risks. The natural logarithm (ln) of the estimated response ratio was calculated from 81 experiments. A meta-analysis was performed on the complete data set, and individual meta-analyses were conducted after stratification by test system, class of vertebrate, exposure route, gender, endpoints, type of literature, formulation, GLY dose and exposure time. A forest plot showed an overall positive association between GLY exposure and its formulations and MN, corroborated by the cumulative effects size. Different responses were observed on mammalian and non-mammalian. Interesting results was noticed in exposure route where oral administration of GLY presented no significance. Exposure by intraperitoneal injection presented the highest MN formation. Pure GLY caused fewer effects than to commercial mixtures, but both presented mutagenic effects. The studies with males presented significant responses, while studies with females were not significant. The cumulative effects size was not clearly related to GLY dose, and was negatively related to exposure time. It can be attributed to different test systems, exposure routes and protocols analyzed. In conclusion, our results support the hypothesis that exposure to GLY and its formulations increases the frequency of MN formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Possible relationship between endocrine disrupting chemicals and hormone dependent gynecologic cancers.

PubMed

Dogan, Selen; Simsek, Tayup

2016-07-01

The effects of the natural and synthetic estrogens have been studied for a long time but the data regarding estrogen related chemicals (endocrine disrupting chemicals, EDCs) and their effects on reproductive system are scarce. EDCs are hormone like agents that are readily present in the environment, which may alter the endocrine system of humans and animals. Approximately 800 chemicals are known or suspected to have the potential to function as EDC. Potential role of EDCs on reproductive disease has gained attention in medical literature in recent years. We hypothesize that exposure to low doses of EDCs in a chronic manner could cause hormone dependent genital cancers including ovarian and endometrial cancer. Long term exposure to low concentrations of EDCs may exert potentiation effect with each other and even with endogenous estrogens and could inhibit enzymes responsible for estrogen metabolism. Exposure time to these EDCs is essential as we have seen from Diethylstilbestrol experience. Dose-response curves of EDCs are also unpredictable. Hence mode of action of EDCs are more complex than previously thought. In the light of these controversies lower doses of EDCs in long term exposure is not harmless. Possibility of this relationship and this hypothesis merit further investigation especially through in vivo studies that could better show the realistic environmental exposure. With the confirmation of our hypothesis, possible EDCs could be identified and eliminated from general use as a public health measure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stringari, James; Nunes, Adriana K.C.; Franco, Jeferson L.

2008-02-15

During the perinatal period, the central nervous system (CNS) is extremely sensitive to metals, including methylmercury (MeHg). Although the mechanism(s) associated with MeHg-induced developmental neurotoxicity remains obscure, several studies point to the glutathione (GSH) antioxidant system as an important molecular target for this toxicant. To extend our recent findings of MeHg-induced GSH dyshomeostasis, the present study was designed to assess the developmental profile of the GSH antioxidant system in the mouse brain during the early postnatal period after in utero exposure to MeHg. Pregnant mice were exposed to different doses of MeHg (1, 3 and 10 mg/l, diluted in drinkingmore » water, ad libitum) during the gestational period. After delivery, pups were killed at different time points - postnatal days (PND) 1, 11 and 21 - and the whole brain was used for determining biochemical parameters related to the antioxidant GSH system, as well as mercury content and the levels of F{sub 2}-isoprostane. In control animals, cerebral GSH levels significantly increased over time during the early postnatal period; gestational exposure to MeHg caused a dose-dependent inhibition of this developmental event. Cerebral glutathione peroxidase (GPx) and glutathione reductase (GR) activities significantly increased over time during the early postnatal period in control animals; gestational MeHg exposure induced a dose-dependent inhibitory effect on both developmental phenomena. These adverse effects of prenatal MeHg exposure were corroborated by marked increases in cerebral F{sub 2}-isoprostanes levels at all time points. Significant negative correlations were found between F{sub 2}-isoprostanes and GSH, as well as between F{sub 2}-isoprostanes and GPx activity, suggesting that MeHg-induced disruption of the GSH system maturation is related to MeHg-induced increased lipid peroxidation in the pup brain. In utero MeHg exposure also caused a dose-dependent increase in the cerebral levels of mercury at birth. Even though the cerebral mercury concentration decreased to nearly basal levels at postnatal day 21, GSH levels, GPx and GR activities remained decreased in MeHg-exposed mice, indicating that prenatal exposure to MeHg affects the cerebral GSH antioxidant systems by inducing biochemical alterations that endure even when mercury tissue levels decrease and become indistinguishable from those noted in pups born to control dams. This study is the first to show that prenatal exposure to MeHg disrupts the postnatal development of the glutathione antioxidant system in the mouse brain, pointing to an additional molecular mechanism by which MeHg induces pro-oxidative damage in the developing CNS. Moreover, our experimental observation corroborates previous reports on the permanent functional deficits observed after prenatal MeHg exposure.« less

Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain

PubMed Central

Stringari, James; Nunes, Adriana KC; Franco, Jeferson L; Bohrer, Denise; Garcia, Solange C; Dafre, Alcir L; Milatovic, Dejan; Souza, Diogo O; Rocha, João BT; Aschner, Michael; Farina, Marcelo

2010-01-01

During the perinatal period, the central nervous system (CNS) is extremely sensitive to metals, including methylmercury (MeHg). Although the mechanism(s) associated with MeHg-induced developmental neurotoxicity remains obscure, several studies point to the glutathione (GSH) antioxidant system as an important molecular target for this toxicant. To extend our recent findings of MeHg-induced GSH dyshomeostasis, the present study was designed to assess the developmental profile of the GSH antioxidant system in the mouse brain during the early postnatal period after in utero exposure to MeHg. Pregnant mice were exposed to different doses of MeHg (1, 3 and 10 mg/L, diluted in drinking water, ad libitum) during the gestational period. After delivery, pups were killed at different time points - postnatal days (PNDs) 1, 11 and 21 - and the whole brain was used for determining biochemical parameters related to the antioxidant GSH system, as well as mercury content and the levels of F2-isoprostane. In control animals, cerebral GSH levels significantly increased over time during the early postnatal period; gestational exposure to MeHg caused a dose-dependent inhibition of this developmental event. Cerebral glutathione peroxidase (GPx) and glutathione reductase (GR) activities significantly increased over time during the early postnatal period in control animals; gestational MeHg exposure induced a dose-dependent inhibitory effect on both developmental phenomena. These adverse effects of prenatal MeHg exposure were corroborated by marked increases in cerebral F2-isoprostanes levels at all time points. Significant negative correlations were found between F2-isoprostanes and GSH, as well as between F2-isoprostanes and GPx activity, suggesting that MeHg-induced disruption of the GSH system maturation is related to MeHg-induced increased lipid peroxidation in the pup brain. In utero MeHg exposure also caused a dose-dependent increase in the cerebral levels of mercury at birth. Even though the cerebral mercury concentration decreased to nearly basal levels at postnatal day 21, GSH levels, GPx and GR activities remained decreased in MeHg-exposed mice, indicating that prenatal exposure to MeHg affects the cerebral GSH antioxidant systems by inducing biochemical alterations that endure even when mercury tissue levels decrease and become indistinguishable from those noted in pups born to control dams. This study is the first to show that prenatal exposure to MeHg disrupts the postnatal development of the glutathione antioxidant system in the mouse brain, pointing to an additional molecular mechanism by which MeHg induces pro-oxidative damage in the developing CNS. Moreover, our experimental observation corroborates previous reports on the permanent functional deficits observed after prenatal MeHg exposure. PMID:18023834

SU-E-CAMPUS-I-04: Automatic Skin-Dose Mapping for An Angiographic System with a Region-Of-Interest, High-Resolution Detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vijayan, S; Rana, V; Setlur Nagesh, S

2014-06-15

Purpose: Our real-time skin dose tracking system (DTS) has been upgraded to monitor dose for the micro-angiographic fluoroscope (MAF), a high-resolution, small field-of-view x-ray detector. Methods: The MAF has been mounted on a changer on a clinical C-Arm gantry so it can be used interchangeably with the standard flat-panel detector (FPD) during neuro-interventional procedures when high resolution is needed in a region-of-interest. To monitor patient skin dose when using the MAF, our DTS has been modified to automatically account for the change in scatter for the very small MAF FOV and to provide separated dose distributions for each detector. Themore » DTS is able to provide a color-coded mapping of the cumulative skin dose on a 3D graphic model of the patient. To determine the correct entrance skin exposure to be applied by the DTS, a correction factor was determined by measuring the exposure at the entrance surface of a skull phantom with an ionization chamber as a function of entrance beam size for various beam filters and kVps. Entrance exposure measurements included primary radiation, patient backscatter and table forward scatter. To allow separation of the dose from each detector, a parameter log is kept that allows a replay of the procedure exposure events and recalculation of the dose components.The graphic display can then be constructed showing the dose distribution from the MAF and FPD separately or together. Results: The DTS is able to provide separate displays of dose for the MAF and FPD with field-size specific scatter corrections. These measured corrections change from about 49% down to 10% when changing from the FPD to the MAF. Conclusion: The upgraded DTS allows identification of the patient skin dose delivered when using each detector in order to achieve improved dose management as well as to facilitate peak skin-dose reduction through dose spreading. Research supported in part by Toshiba Medical Systems Corporation and NIH Grants R43FD0158401, R44FD0158402 and R01EB002873.« less

Biomarkers of oxidative stress study V: ozone exposure of rats and its effect on lipids, proteins, and DNA in plasma and urine.

PubMed

Kadiiska, Maria B; Basu, Samar; Brot, Nathan; Cooper, Christopher; Saari Csallany, A; Davies, Michael J; George, Magdalene M; Murray, Dennis M; Jackson Roberts, L; Shigenaga, Mark K; Sohal, Rajindar S; Stocker, Roland; Van Thiel, David H; Wiswedel, Ingrid; Hatch, Gary E; Mason, Ronald P

2013-08-01

Ozone exposure effect on free radical-catalyzed oxidation products of lipids, proteins, and DNA in the plasma and urine of rats was studied as a continuation of the international Biomarker of Oxidative Stress Study (BOSS) sponsored by NIEHS/NIH. The goal was to identify a biomarker for ozone-induced oxidative stress and to assess whether inconsistent results often reported in the literature might be due to the limitations of the available methods for measuring the various types of oxidative products. The time- and dose-dependent effects of ozone exposure on rat plasma lipid hydroperoxides, malondialdehyde, F2-isoprostanes, protein carbonyls, methionine oxidation, and tyrosine- and phenylalanine oxidation products, as well as urinary malondialdehyde and F2-isoprostanes were investigated with various techniques. The criterion used to recognize a marker in the model of ozone exposure was that a significant effect could be identified and measured in a biological fluid seen at both doses at more than one time point. No statistically significant differences between the experimental and the control groups at either ozone dose and time point studied could be identified in this study. Tissue samples were not included. Despite all the work accomplished in the BOSS study of ozone, no available product of oxidation in biological fluid has yet met the required criteria of being a biomarker. The current negative findings as a consequence of ozone exposure are of great importance, because they document that in complex systems, as the present in vivo experiment, the assays used may not provide meaningful data of ozone oxidation, especially in human studies. Published by Elsevier Inc.

Biomarkers of Oxidative Stress Study V: Ozone exposure of rats and its effect on lipids, proteins and DNA in plasma and urine

PubMed Central

Kadiiska, Maria B.; Basu, Samar; Brot, Nathan; Cooper, Christopher; Csallany, A. Saari; Davies, Michael J.; George, Magdalene M.; Murray, Dennis M.; Roberts, L. Jackson; Shigenaga, Mark K.; Sohal, Rajindar S.; Stocker, Roland; Van Thiel, David H.; Wiswedel, Ingrid; Hatch, Gary E.; Mason, Ronald P.

2014-01-01

Ozone exposure effect on free radical-catalyzed oxidation products of lipids, proteins and DNA in the plasma and urine of rats was studied as a continuation of the international Biomarker of Oxidative Stress Study (BOSS) sponsored by NIEHS/NIH. The goal was to identify a biomarker for ozone-induced oxidative stress and to assess whether inconsistent results often reported in the literature might be due to the limitations of the available methods for measuring the various types of oxidative products. The time and dose-dependent effects of ozone exposure on rat plasma lipid hydroperoxides, malondialdehyde, F2-isoprostanes, protein carbonyls, methionine oxidation, tyrosine- and phenylalanine oxidation products, as well as urinary malondialdehyde and F2-isoprostanes were investigated with various techniques. The criterion used to recognize a marker in the model of ozone exposure was that a significant effect could be identified and measured in a biological fluid seen at both doses at more than one time point. No statistically significant differences between the experimental and control groups at either ozone dose and time point studied could be identified in this study. Tissue samples were not included. Despite all the work accomplished in the BOSS study of ozone, no available product of oxidation in biological fluid has yet met the required criteria of being a biomarker. The current negative findings as a consequence of ozone exposure are of great importance, because they document that in complex systems, as the present in vivo experiment, the assays used may not provide meaningful data of ozone oxidation, especially in human studies. PMID:23608465

Development of methods for avian oil toxicity studies using the double crested cormorant (Phalacrocorax auritus).

PubMed

Cunningham, Fred; Dean, Karen; Hanson-Dorr, Katie; Harr, Kendal; Healy, Kate; Horak, Katherine; Link, Jane; Shriner, Susan; Bursian, Steven; Dorr, Brian

2017-07-01

Oral and external dosing methods replicating field exposure were developed using the double crested cormorant (DCCO) to test the toxicity of artificially weathered Deepwater Horizon Mississippi Canyon 252 oil. The majority of previous oil dosing studies conducted on wild-caught birds used gavage methods to dose birds with oil and determine toxicity. However, rapid gut transit time of gavaged oil likely reduces oil absorption. In the present studies, dosing relied on injection of oil into live feeder fish for oral dosing of these piscivorous birds, or applying oil to body contour feathers resulting in transdermal oil exposure and oral exposure through preening. Both oral and external oil dosing studies identified oil-related toxicity endpoints associated with oxidative stress such as hemolytic anemia, liver and kidney damage, and immuno-modulation or compromise. External oil application allowed for controlled study of thermoregulatory stress as well. Infrared thermal images indicated significantly greater surface temperatures and heat loss in treated birds following external oil applications; however, measurements collected by coelomically implanted temperature transmitters showed that internal body temperatures were stable over the course of the study period. Birds exposed to oil externally consumed more fish than control birds, indicating metabolic compensation for thermal stress. Conversely, birds orally dosed with oil experienced hypothermia and consumed less fish compared to control birds. Published by Elsevier Inc.

Neuropsychological exploration of alleged mold neurotoxicity.

PubMed

Reinhard, Matthew J; Satz, Paul; Scaglione, Cris A; D'Elia, Louis F; Rassovsky, Yuri; Arita, Anthony A; Hinkin, Charles H; Thrasher, Delaney; Ordog, Gary

2007-05-01

Cognitive and emotional correlates of toxic mold exposure and potential dose-response effects for both outcomes were investigated. Self-reported length of exposure, time since last exposure, and serum immunoglobulin (IgG) levels were assessed. Despite CNS complaints often seen with mold exposed individuals, overall results did not uncover concomitant cognitive deficits suggested in previous studies or a significant reduction in intellectual functioning. Fewer subjects were excluded as result of failing effort/motivation assessment than expected. Correlations of IgG and cognitive function are discussed. A dose-effect for self-reported length of exposure and cognitive outcome was not seen. The sample's overall Minnesota Multiphasic Personality Inventory II (MMPI-2) profile indicated elevations on scales 1, 2, 3, 7 and 8. MMPI-2 clinical scales 1 and 3 were significantly correlated with length of exposure. The MMPI-2 may be sensitive to increasing physical and emotional sequelae as length of exposure increases. A potential subgroup of cognitively impaired outliers within mold exposure litigants is explored. Limitations of self-reported and objective measurements for mold exposure and exploratory statistical methodology are discussed.

Ingestion, inhalation, and dermal exposures to chloroform and trichloroethene from tap water.

PubMed Central

Weisel, C P; Jo, W K

1996-01-01

Individuals are exposed to volatile compounds present in tap water by ingestion, inhalation, and dermal absorption. Traditional risk assessments for water often only consider ingestion exposure to toxic chemicals, even though showering has been shown to increase the body burden of certain chemicals due to inhalation exposure and dermal absorption. We collected and analyzed time-series samples of expired alveolar breath to evaluate changes in concentrations of volatile organic compounds being expired, which reflects the rate of change in the bloodstream due to expiration, metabolism, and absorption into tissues. Analysis of chloroform and trichloethene in expired breath, compounds regulated in water, was also used to determine uptake from tap water by each route (inhalation, ingestion, or absorption). Each route of exposure contributed to the total exposure of these compounds from daily water use. Further, the ingestion dose was completely metabolized before entering the bloodstream, whereas the dose from the other routes was dispersed throughout the body. Thus, differences in potential biologically effective doses depend on route, target organ, and whether the contaminant or metabolite is the biologically active agent. Images Figure 1. A Figure 1. B Figure 1. C Figure 2. A Figure 2. B PMID:8834861

Animal studies of life shortening and cancer risk from space radiation

NASA Astrophysics Data System (ADS)

Wood, D. H.; Yochmowitz, M. G.; Hardy, K. A.; Salmon, Y. L.

The U. S. Air Force study of the delayed effects of single, total body exposures to simulated space radiation in rhesus monkeys is now in its 21st year. Observations on 301 irradiated and 57 age-matched control animals indicate that life expectancy loss from exposure to protons in the energy range encountered in the Van Allen belts and solar proton events can be expressed as a logarithmic function of the dose. The primary causes of life shortening are cancer and endometriosis (an abnormal proliferation of the lining of the uterus in females). Life shortening estimates permit comparison of the risk associated with space radiation exposures to be compared with that of other occupational and environmental hazards, thereby facilitating risk/benefit decisions in the planning and operational phases of manned space missions. Calculations of the relative risk of fatal cancers in the irradiated subjects reveal that the total body surface dose required to double the risk of death from cancer over a 20-year post exposure period varies with the linear energy transfer (LET) of the radiation. The ability to determine the integrated dose and LET spectrum in space radiation exposures of human is, therefore, critical to the assessment of life-time cancer risk.

APPLICATION AND USE OF DOSE ESTIMATING EXPOSURE MODEL (DEEM) FOR DOSE COMPARISONS AFTER EXPOSURE TO TRICHLOROETHYLENE (TCE)

EPA Science Inventory

Route-to-route extrapolations are a crucial step in many risk assessments. Often the doses which result In toxicological end points in one route must be compared with doses resulting from typical environmental exposures by another route. In this case we used EPA's Dose Estimati...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kitabatake, T.; Kaneko, M.; Takagi, Y.

Dosimetry was used to estimate the radiation dose received by dertal patients and dentists in dental clinics in Japan, and the results were compared with those obtained by an enlargement technique. The phantom of paraffin used for measuring exposure doses was based on a whole-body plaster of panis cast of a Japanese of medium size. The lungs in the phantom were made of cork with a specific gravity of 0.2, and three holes were constructed in the oral cavity, lower abdomen (ovary region), and testicular region for insertion of a dosimeter. Since in most dental clinics in Japan the x-raymore » apparatus is installed in the corner of the treatment room without any Pb protection, dose distribution of scattered x rays was also surveyed. Four types of x-ray units were used, and measurement was performed at distances 50 to 200 cm at levels of 50 and 100 cm from the floor. The gonads received a dose of about 0.5 to 3 mr per exposure in males, and 0.03 to 1 mr in females. Patients received radiation doses of 10 to l000 mr per exposure at the eye lens, 1500 mr on the nasal apex, and 500 mr on the thyroid region. Not less than 100 mr of radiation was distributed in the regions of the pharynx and cervical spine. For dentists holding the film in the patient's mouth, about 1 to 3 r were received per exposure. They also received whole-body irradiation of scattered rays of about 500 to 2000 mr/hr. Since in Japan, even at present, the dentist usually holds the fllm in the patient's mouth during radiography, and if he conducts dental radiography 10 times a day, he should receive 10 to 30 r on his hands a day, or 3000 to 9000 r a year. Furthermore, the dentist standing near the patient is exposed to scattered rays of about 1.4 mr per exposure. Therefore 11 exposures per day give the upper limit of irradiation dose according to maximum permissible dose. The long-cone method, it is suggested, is of value not only for making enlargement radiograms but also for diminishing the exposure dose of dentists since it prevents the production of scattered rays. (BBB)« less

THE UNIQUE VALUE OF BREATH BIOMARKERS FOR ESTIMATING PHAMACOKINETIC RATE CONSTANTS AND BODY BURDEN FROM RANDOM/INTERMITTENT DOSE

EPA Science Inventory

Biomarker measurements are used in three ways: 1) evaluating the time course and distribution of a chemical in the body, 2) estimating previous exposure or dose, and 3) assessing disease state. Blood and urine measurements are the primary methods employed. Of late, it has been ...

Dose-response relationship between hand-transmitted vibration and hand-arm vibration syndrome in a tropical environment.

PubMed

Su, Anselm Ting; Maeda, Setsuo; Fukumoto, Jin; Darus, Azlan; Hoe, Victor C W; Miyai, Nobuyuki; Isahak, Marzuki; Takemura, Shigeki; Bulgiba, Awang; Yoshimasu, Kouichi; Miyashita, Kazuhisa

2013-07-01

The dose-response relationship for hand-transmitted vibration has been investigated extensively in temperate environments. Since the clinical features of hand-arm vibration syndrome (HAVS) differ between the temperate and tropical environment, we conducted this study to investigate the dose-response relationship of HAVS in a tropical environment. A total of 173 male construction, forestry and automobile manufacturing plant workers in Malaysia were recruited into this study between August 2011 and 2012. The participants were interviewed for history of vibration exposure and HAVS symptoms, followed by hand functions evaluation and vibration measurement. Three types of vibration doses-lifetime vibration dose (LVD), total operating time (TOT) and cumulative exposure index (CEI)-were calculated and its log values were regressed against the symptoms of HAVS. The correlation between each vibration exposure dose and the hand function evaluation results was obtained. The adjusted prevalence ratio for finger tingling and numbness was 3.34 (95% CI 1.27 to 8.98) for subjects with lnLVD≥20 ln m(2) s(-4) against those <16 ln m(2) s(-4). Similar dose-response pattern was found for CEI but not for TOT. No subject reported white finger. The prevalence of finger coldness did not increase with any of the vibration doses. Vibrotactile perception thresholds correlated moderately with lnLVD and lnCEI. The dose-response relationship of HAVS in a tropical environment is valid for finger tingling and numbness. The LVD and CEI are more useful than TOT when evaluating the dose-response pattern of a heterogeneous group of vibratory tools workers.

Fluoxetine exposure impacts boldness in female Siamese fighting fish, Betta splendens.

PubMed

Dzieweczynski, Teresa L; Kane, Jessica L; Campbell, Brennah A; Lavin, Lindsey E

2016-01-01

The present study examined the effects of the selective serotonin reuptake inhibitor, fluoxetine, on the behavior of female Siamese fighting fish, Betta splendens, in three different boldness assays (Empty Tank, Novel Environment, Social Tendency). When females were unexposed to fluoxetine, boldness was consistent within a context and correlated across assays. Fluoxetine exposure affected behavior within and among individuals on multiple levels. Exposure reduced overall boldness levels, made females behave in a less consistent manner, and significantly reduced correlations over time and across contexts. Fluoxetine exerted its effects on female Betta splendens behavior in a dose-dependent fashion and these effects persisted even after females were housed in clean water. If fluoxetine exposure impacts behaviors such as exploration that are necessary to an individual’s success, this may yield evolutionary consequences. In conclusion, the results show that fluoxetine exposure alters behavior beyond the level of overall response and highlights the importance of studying the behavioral effects of inadvertent pharmaceutical exposure in multiple contexts and with different dosing regimes.

Modeling the acute health effects of astronauts from exposure to large solar particle events.

PubMed

Hu, Shaowen; Kim, Myung-Hee Y; McClellan, Gene E; Cucinotta, Francis A

2009-04-01

Radiation exposure from Solar Particle Events (SPE) presents a significant health concern for astronauts for exploration missions outside the protection of the Earth's magnetic field, which could impair their performance and result in the possibility of failure of the mission. Assessing the potential for early radiation effects under such adverse conditions is of prime importance. Here we apply a biologically based mathematical model that describes the dose- and time-dependent early human responses that constitute the prodromal syndromes to consider acute risks from SPEs. We examine the possible early effects on crews from exposure to some historically large solar events on lunar and/or Mars missions. The doses and dose rates of specific organs were calculated using the Baryon radiation transport (BRYNTRN) code and a computerized anatomical man model, while the hazard of the early radiation effects and performance reduction were calculated using the Radiation-Induced Performance Decrement (RIPD) code. Based on model assumptions we show that exposure to these historical events would cause moderate early health effects to crew members inside a typical spacecraft or during extra-vehicular activities, if effective shielding and medical countermeasure tactics were not provided. We also calculate possible even worse cases (double intensity, multiple occurrences in a short period of time, etc.) to estimate the severity, onset and duration of various types of early illness. Uncertainties in the calculation due to limited data on relative biological effectiveness and dose-rate modifying factors for protons and secondary radiation, and the identification of sensitive sites in critical organs are discussed.

The Effect of Dose Rate on Composite Durability When Exposed to a Simulated Long-Term Lunar Radiation Environment

NASA Technical Reports Server (NTRS)

Rojdev, Kristina; O'Rourke, Mary Jane; Hill, Charles; Nutt, Steven; Atwell, William

2011-01-01

Human exploration of space beyond low Earth orbit (LEO) requires a safe living and working environment for crew. Composite materials are one type of material being investigated by NASA as a multi-functional structural approach to habitats for long-term use in space or on planetary surfaces with limited magnetic fields and atmosphere. These materials provide high strength with the potential for decreased weight and increased radiation protection of crew and electronics when compared with conventional aluminum structures. However, these materials have not been evaluated in a harsh radiation environment, as would be experienced outside of LEO or on a planetary surface. Thus, NASA has been investigating the durability of select composite materials in a long-term radiation environment. Previously, NASA exposed composite samples to a simulated, accelerated 30-year radiation treatment and tensile stresses similar to those of a habitat pressure vessel. The results showed evidence of potential surface oxidation and enhanced cross-linking of the matrix. As a follow-on study, we performed the same accelerated exposure alongside an exposure with a decreased dose rate. The slower dose ]rate is comparable to a realistic scenario, although still accelerated. Strain measurements were collected during exposure and showed that with a fastdose rate, the strain decreased with time, but with a slow ]dose rate, the strain increased with time. After the radiation exposures, samples were characterized via tensile tests, flexure tests, Fourier Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC). The results of these tests will be discussed.

Characterization and control of EUV scanner dose uniformity and stability

NASA Astrophysics Data System (ADS)

Robinson, Chris; Corliss, Dan; Meli, Luciana; Johnson, Rick

2018-03-01

The EUV source is an impressive feat of engineering that provides 13.5 nm radiation by vaporizing tin droplets with a high power CO2 laser and focusing the photons produced in the resultant plasma into the scanner illumination system. Great strides have been made in addressing the many potential stability challenges, but there are still residual spatial and temporal dose non-uniformity signatures. Since even small dose errors can impact the yieldable process window for the advanced lithography products that are exposed on EUV scanners it is crucial to monitor and control the dose variability. Using on-board metrology, the EUV scanner outputs valuable metrics that provide real time insight into the dose performance. We have supplemented scanner data collection with a wafer based methodology that provides high throughput, high sensitivity, quantitative characterization of the EUV scanner dose delivery. The technique uses open frame EUV exposures, so it is exclusive of lithographic pattern imaging, exclusive of lithographic mask pattern and not limited by placement of metrology features. Processed wafers are inspected rapidly, providing 20,000 pixels of detail per exposure field in approximately one minute. Exposing the wafer on the scanner with a bit less than the resist E0 (open frame clearing dose) results in good sensitivity to small variations in the EUV dose delivered. The nominal exposure dose can be modulated by field to calibrate the inspection results and provide quantitative assessment of variations with < 1% sensitivity. This technique has been used for dose uniformity assessments. It is also being used for long term dose stability monitoring and has proven valuable for short term dose stability follow up investigations.

Solar UV radiation exposure of seamen - Measurements, calibration and model calculations of erythemal irradiance along ship routes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feister, Uwe; Meyer, Gabriele; Kirst, Ulrich

2013-05-10

Seamen working on vessels that go along tropical and subtropical routes are at risk to receive high doses of solar erythemal radiation. Due to small solar zenith angles and low ozone values, UV index and erythemal dose are much higher than at mid-and high latitudes. UV index values at tropical and subtropical Oceans can exceed UVI = 20, which is more than double of typical mid-latitude UV index values. Daily erythemal dose can exceed the 30-fold of typical midlatitude winter values. Measurements of erythemal exposure of different body parts on seamen have been performed along 4 routes of merchant vessels.more » The data base has been extended by two years of continuous solar irradiance measurements taken on the mast top of RV METEOR. Radiative transfer model calculations for clear sky along the ship routes have been performed that use satellite-based input for ozone and aerosols to provide maximum erythemal irradiance and dose. The whole data base is intended to be used to derive individual erythemal exposure of seamen during work-time.« less

Single-dose pharmacokinetic properties of esomeprazole in children aged 1 - 11 years with endoscopically proven GERD: a randomized, open-label study.

PubMed

Youssef, Nader N; Tron, Eduardo; Tolia, Vasundhara; Hamer-Maansson, Jennifer E; Lundborg, Per; Illueca, Marta

2014-11-01

To assess the overall exposure after a single dose of esomeprazole in children with gastroesophageal reflux disease (GERD). Oral esomeprazole administered as an intact capsule with 30 - 180 mL of water, or as an opened capsule mixed with as much as 1 tablespoon of applesauce followed by 30 - 180 mL of water. In this randomized, open-label study of children aged 1 - 11 years with endoscopically proven GERD, patients weighing 8 - < 20 kg were randomized to a single 5- or 10-mg oral dose of esomeprazole, and patients weighing >= 20 kg were randomized to a single 10- or 20-mg oral dose of esomeprazole. Esomeprazole exposure (AUC(0-∞)), AUC from zero to last measurable concentration (AUC(0-t)), maximum plasma concentration (C(max)), time to C(max) (t(max)), terminal-phase half-life, apparent oral clearance, and apparent volume of distribution were determined. 28 patients were randomized to receive esomeprazole: 14 patients weighing 8 to < 20 kg received esomeprazole 5 mg (n = 7) or 10 mg (n = 7), and 14 patients weighing ≥20 kg received esomeprazole 10 mg (n = 6) or 20 mg (n = 8). Children weighing 8 - < 20 kg had a 1.8-fold higher exposure with the 10-mg vs. 5-mg dose (AUC(0-∞), 1.32 vs. 0.73 μmol·h/L, respectively); children weighing ≥ 20 kg had a 4.4-fold higher exposure with the 20-mg vs. 10-mg dose (AUC(0-∞), 3.06 vs. 0.69 μmol·h/L). C(max) was 2.2-fold higher for the 10-mg vs. 5-mg dose (8 to < 20 kg) and 2.4-fold higher for the 20-mg vs.10-mg dose (>= 20 kg). The pharmacokinetics of single-dose esomeprazole were dose-dependent in children weighing >= 20 kg but not in children weighing 8 to < 20 kg.

Defining the radiation "scatter cloud" in the interventional suite.

PubMed

Haqqani, Omar P; Agarwal, Prakhar K; Halin, Neil M; Iafrati, Mark D

2013-11-01

We hypothesized that fluoroscopic imaging creates radiation fields that are unevenly scattered throughout the endovascular suite. We sought to quantify the radiation dose spectrum at various locations during imaging procedures and to represent this in a clinically useful manner. Digital subtraction imaging (Innova 4100; GE Healthcare, Waukesha, Wisc) of the abdomen and pelvis was performed on a cadaver in anteroposterior, left lateral, and right anterior oblique 45° projections. Radiation exposure was monitored in real time with DoseAware dosimeters (Phillips, Houston, Tex) in eight radial projections at distances of 2, 4, and 6 ft from the center of the imaged field, each at 5-ft heights from the floor. Three to five consecutive data points were collected for each location. At most positions around the angiographic table, radiation exposure decreased as the distance from the source emitter increased; however, the intensity of the exposure varied dramatically around the axis of imaging. With anteroposterior imaging, the radiation fields have symmetric dumbbell shapes, with maximal exposure perpendicular to the table at the level of the gantry. Peak levels at 4 and 6 ft from the source emitter were 2.4 times and 3.4 times higher, respectively, than predicted based on the inverse square law. Maximal radiation exposure was measured in the typical operator position 2 ft away and perpendicular to the table (4.99 mSv/h). When the gantry was rotated 45° and 90°, the radiation fields shifted, becoming more asymmetric, with increasing radiation doses to 10.9 and 69 mSv/h, respectively, on the side of the emitter. Minimal exposure is experienced along the axis of the table, decreasing with distance from the source (<0.77 mSv/h). Quantifiable and reproducible radiation scatter is created during interventional procedures. Radiation doses vary widely around the perimeter of the angiography table and change according to imaging angles. These data are easily visualized using contour plots and scatter three-dimensional mesh plots. Rather than the concentric circles predicted by the inverse square law, these data more closely resemble a "scatter cloud." Knowledge of the actual exposure levels within the endovascular environment may help in mitigating these risks to health care providers. Copyright © 2013. Published by Mosby, Inc.

SHEDS-PM: A POPULATION EXPOSURE MODEL FOR PREDICTING DISTRIBUTIONS OF PM EXPOSURE AND DOSE FROM BOTH OUTDOOR AND INDOOR SOURCES

EPA Science Inventory

The US EPA National Exposure Research Laboratory (NERL) has developed a population exposure and dose model for particulate matter (PM), called the Stochastic Human Exposure and Dose Simulation (SHEDS) model. SHEDS-PM uses a probabilistic approach that incorporates both variabi...

Exposure of airport workers to radiation from shipments of radioactive materials. A review of studies conducted at six major airports. Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shapiro, J.

1976-02-01

The radiation exposure of airport workers handling shipments of radioactive materials was studied at six airports. Descriptions were obtained of the handling and arrangement of the packages, dose distributions were mapped around groupings of packages, and doses received by workers were evaluated both on the basis of time-motion studies and through readings of personal monitoring devices. Results of dosimeters worn over extended periods indicated that no workers were expected to receive exposures in excess of 500 millirems per year and most were expected to receive less than 100 millirems per year. No evidence was found in any of the sixmore » airport studies to suggest that members of the public received any exposure of significance relative to the natural background radiation.« less

Growth and development of larval green frogs (Rana clamitans) exposed to multiple doses of an insecticide

USGS Publications Warehouse

Boone, M.D.; Bridges, C.M.; Rothermel, B.B.

2001-01-01

Our objective was to determine how green frogs (Rana clamitans) are affected by multiple exposures to a sublethal level of the carbamate insecticide, carbaryl, in outdoor ponds. Tadpoles were added to 1,000-1 ponds at a low or high density which were exposed to carbaryl 0, 1, 2, or 3 times. Length of the larval period, mass, developmental stage, tadpole survival, and proportion metamorphosed were used to determine treatment effects. The frequency of dosing affected the proportion of green frogs that reached metamorphosis and the developmental stage of tadpoles. Generally, exposure to carbaryl increased rates of metamorphosis and development. The effect of the frequency of carbaryl exposure on development varied with the density treatment; the majority of metamorphs and the most developed tadpoles came from high-density ponds exposed to carbaryl 3 times. This interaction suggests that exposure to carbaryl later in the larval period stimulated metamorphosis, directly or indirectly, under high-density conditions. Our study indicates that exposure to a contaminant can lead to early initiation of metamorphosis and that natural biotic factors can mediate the effects of a contaminant in the environment.

Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields

NASA Astrophysics Data System (ADS)

Ghita, Mihaela; Coffey, Caroline B.; Butterworth, Karl T.; McMahon, Stephen J.; Schettino, Giuseppe; Prise, Kevin M.

2016-01-01

To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions.

Estimations of the lethal and exposure doses for representative methanol symptoms in humans.

PubMed

Moon, Chan-Seok

2017-01-01

The aim of this review was to estimate the lethal and exposure doses of a representative symptom (blindness) of methanol exposure in humans by reviewing data from previous articles. Available articles published from 1970 to 2016 that investigated the dose-response relationship for methanol exposure (i.e., the exposure concentration and the biological markers/clinical symptoms) were evaluated; the MEDLINE and RISS (Korean search engine) databases were searched. The available data from these articles were carefully selected to estimate the range and median of a lethal human dose. The regression equation and correlation coefficient (between the exposure level and urinary methanol concentration as a biological exposure marker) were assumed from the previous data. The lethal human dose of pure methanol was estimated at 15.8-474 g/person as a range and as 56.2 g/person as the median. The dose-response relationship between methanol vapor in ambient air and urinary methanol concentrations was thought to be correlated. An oral intake of 3.16-11.85 g/person of pure methanol could cause blindness. The lethal dose from respiratory intake was reported to be 4000-13,000 mg/l. The initial concentration of optic neuritis and blindness were shown to be 228.5 and 1103 mg/l, respectively, for a 12-h exposure. The concentration of biological exposure indices and clinical symptoms for methanol exposure might have a dose-response relationship according to previous articles. Even a low dose of pure methanol through oral or respiratory exposure might be lethal or result in blindness as a clinical symptom.

Dedicated high dose rate 192Ir brachytherapy radiation fields for in vitro cell exposures at variable source-target cell distances: killing of mammalian cells depends on temporal dose rate fluctuation

NASA Astrophysics Data System (ADS)

Veigel, Cornelia; Hartmann, Günther H.; Fritz, Peter; Debus, Jürgen; Weber, Klaus-Josef

2017-02-01

Afterloading brachytherapy is conducted by the stepwise movement of a radioactive source through surgically implanted applicator tubes where at predefined dwell positions calculated dwell times optimize spatial dose delivery with respect to a planned dose level. The temporal exposure pattern exhibits drastic fluctuations in dose rate at a given coordinate and within a single treatment session because of the discontinuous and repeated source movement into the target volume. This could potentially affect biological response. Therefore, mammalian cells were exposed as monolayers to a high dose rate 192Ir source by utilizing a dedicated irradiation device where the distance between a planar array of radioactive source positions and the plane of the cell monolayer could be varied from 2.5 mm to 40 mm, thus varying dose rate pattern for any chosen total dose. The Gammamed IIi afterloading system equipped with a nominal 370 GBq (10 Ci) 192-Ir source was used to irradiate V79 Chinese hamster lung fibroblasts from both confluent and from exponential growth phase with dose up to 12 Gy (at room temperature, total exposure not exceeding 1 h). For comparison, V79 cells were also exposed to 6 MV x-rays from a clinical linear accelerator (dose rate of 2.5 Gy min-1). As biological endpoint, cell survival was determined by standard colony forming assay. Dose measurements were conducted with a diamond detector (sensitive area 7.3 mm2), calibrated by means of 60Co radiation. Additionally, dose delivery was simulated by Monte Carlo calculations using the EGSnrc code system. The calculated secondary electron fluence spectra at the cell location did not indicate a significant change of radiation quality (i.e. higher linear energy transfer) at the lower distances. Clonogenic cell survival curves obtained after brachytherapy exhibited an altered biological response compared to x-rays which was characterized by a significant reduction of the survival curve shoulder when dose rate fluctuations were high. Therefore, also for the time scale of the present investigation, cellular effects of radiation are not invariant to the temporal pattern in dose rate. We propose that with high dose rate variation the cells activate less efficiently their DNA damage response than after continuous irradiation.

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure.

PubMed

Tucker, Deirdre K; Macon, Madisa B; Strynar, Mark J; Dagnino, Sonia; Andersen, Erik; Fenton, Suzanne E

2015-07-01

Perfluorooctanoic acid (PFOA) is a developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1mg/kg) has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. Also an evaluation of female serum hormone levels and pubertal timing onset revealed no effects of PFOA compared to controls in either strain. These data suggest that the mammary gland is more sensitive to early low level PFOA exposures compared to other pubertal endpoints, regardless of strain. Published by Elsevier Inc.

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure

PubMed Central

Tucker, Deirdre K.; Macon, Madisa B.; Strynar, Mark J.; Dagnino, Sonia; Andersen, Erik; Fenton, Suzanne E.

2015-01-01

Perfluorooctanoic acid (PFOA) is a known developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1 mg/kg), however, has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Mouse pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in exposed female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. In contrast, an evaluation of serum hormone levels and pubertal timing onset in the same offspring revealed no effects of PFOA compared to controls in either strain. Therefore, our data suggest that the mammary gland is more sensitive to the effects of early low level PFOA exposures compared to other pubertal endpoints, regardless of strain. PMID:25499722

Modelling of aircrew radiation exposure from galactic cosmic rays and solar particle events.

PubMed

Takada, M; Lewis, B J; Boudreau, M; Al Anid, H; Bennett, L G I

2007-01-01

Correlations have been developed for implementation into the semi-empirical Predictive Code for Aircrew Radiation Exposure (PCAIRE) to account for effects of extremum conditions of solar modulation and low altitude based on transport code calculations. An improved solar modulation model, as proposed by NASA, has been further adopted to interpolate between the bounding correlations for solar modulation. The conversion ratio of effective dose to ambient dose equivalent, as applied to the PCAIRE calculation (based on measurements) for the legal regulation of aircrew exposure, was re-evaluated in this work to take into consideration new ICRP-92 radiation-weighting factors and different possible irradiation geometries of the source cosmic-radiation field. A computational analysis with Monte Carlo N-Particle eXtended Code was further used to estimate additional aircrew exposure that may result from sporadic solar energetic particle events considering real-time monitoring by the Geosynchronous Operational Environmental Satellite. These predictions were compared with the ambient dose equivalent rates measured on-board an aircraft and to count rate data observed at various ground-level neutron monitors.

Recovery from welding-fume-exposure-induced MRI T1 signal intensities after cessation of welding-fume exposure in brains of cynomolgus monkeys.

PubMed

Han, Jeong Hee; Chung, Yong Hyun; Park, Jung Duck; Kim, Choong Yong; Yang, Seoung Oh; Khang, Hyun Soo; Cheong, Hae Kwan; Lee, Jong Seong; Ha, Chang Soo; Song, Chang-Woo; Kwon, Il Hoon; Sung, Jae Hyuck; Heo, Jeong Doo; Kim, Na-Young; Huang, Mingai; Cho, Myung Haing; Yu, Il Je

2008-09-01

The shortening of the MRI T1 relaxation time, indicative of a high signal intensity in a T1-weighted MRI, is known as a useful biomarker for Mn exposure after short-term welding-fume exposure. A previous monkey experimental study found that the T1 relaxation times decreased time-dependently after exposure, and a visually detectable high signal intensity appeared after 150 days of exposure. The nadir for the shortening of the T1 relaxation time was also previously found to correspond well with the blood Mn concentration in welders, suggesting a correlation between a prolonged high blood Mn concentration and shortened T1 relaxation time. Accordingly, to clarify the clearance of the brain Mn concentration after the cessation of welding-fume exposure, cynomolgus monkeys were assigned to 3 groups-unexposed, low dose (31 mg/m(3) total suspended particulate (TSP), 0.9 mg Mn/m(3)), and high dose (62 mg/m(3) TSP, 1.95 mg Mn/m(3))-and exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h per day for 8 mo in an inhalation chamber system equipped with an automatic fume generator. After reaching the peak MRI T1 signal intensity (shortest T1 relaxation time), the monkeys were allowed to recover by ceasing the welding-fume exposure. Within 2 mo, the MRI T1 signal intensities for the exposed monkeys returned to nearly the same level as those for the unexposed monkeys, indicating the potential for recovery from a high MRI T1 signal intensity induced by welding-fume exposure, even after prolonged exposure. Clearance of the Mn tissue concentration was also demonstrated in the globus pallidus, plus other tissues from the brain, liver, spleen, and blood. In contrast, there was no clearance of the lung concentrations of Mn, indicating that a soluble form of Mn was transported to the blood and brain. Therefore, the solubility of Mn in welding fumes would appear to be an important determinant as regards the retention of blood Mn levels and brain tissue Mn concentrations in welders.

Evaluation of the single-dose pharmacokinetics of bilastine in subjects with various degrees of renal insufficiency.

PubMed

Lasseter, Kenneth C; Sologuren, Ander; La Noce, Anna; Dilzer, Stacy C

2013-09-01

Bilastine is a novel second-generation H1 antihistamine, which has not shown sedative or cardiotoxic effects in clinical trials and in post-marketing experience so far, developed for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. It has recently been granted marketing authorization for these therapeutic indications in adults and adolescents at a once-daily oral dose of 20 mg in several European countries. This study was conducted to determine the pharmacokinetics of bilastine at a single oral dose of 20 mg in renally impaired subjects. The need for a dose adjustment in patients with renal insufficiency was assessed by comparing the exposure to bilastine in these subjects with the estimated exposure of a dose corresponding to the safety margin. The study was an open-label, single-dose, parallel-group study of the pharmacokinetics and safety of a single dose of bilastine. The study was conducted as an in-patient setting at a clinical pharmacology facility. A total of 24 male or female subjects aged 18-80 years were to be enrolled in four groups of six subjects each. The groups were as follows: (1) healthy [glomerular filtration rate (GFR) >80 mL/min/1.73 m(2)]; (2) mild renal insufficiency (GFR 50-80 mL/min/1.73 m(2)); (3) moderate renal insufficiency (GFR 30-50 mL/min/1.73 m(2)); and (4) severe renal insufficiency (GFR ≤30 mL/min/1.73 m(2)). A single 20 mg bilastine tablet was administered in a fasted state. Blood and urine samples were collected from pre-dose up to 72 h post-dose for bilastine pharmacokinetic analysis. Pharmacokinetic results were summarized using appropriate descriptive statistics. There was a clear trend of increasing area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C(max)) through the groups 1-4. The mean AUC from time zero to infinity (AUC(∞)) ranged from 737.4 to 1708.5 ng·h/mL in healthy subjects and severely impaired subjects, respectively. No significant differences among groups in median time to reach Cmax (tmax) or in the mean terminal disposition rate constants for bilastine were found. Renal and plasma clearance paralleled GFR. In all groups of renally impaired subjects the corresponding 90 % confidence interval of both AUC(∞) and AUC from time zero to time of last measurable plasma concentration (AUC(last)) were not within the 0.8-1.25 interval, indicating that bioequivalence between groups could not be demonstrated. The majority of bilastine was excreted within the first 12 h, and elimination was essentially complete by 72 h. An oral dose of bilastine (20 mg) was well-tolerated in renal insufficiency, despite the increase in exposure. The oral plasma clearance to renal clearance ratio [(CL(P)/F)/CL(R)] was approximately equal in the different groups, suggesting that renal excretion was the main elimination route for bilastine, and no alternative elimination routes were used even in severe renal insufficiency. Although exposure to bilastine was higher in renally impaired subjects, it remained well within the safety margins, thus allowing the conclusion that a 20-mg daily dose can be safely administered to subjects with different degrees of renal insufficiency without the need for dose adjustments.

A Multi-Compartment, Single and Multiple Dose Pharmacokinetic Study of the Vaginal Candidate Microbicide 1% Tenofovir Gel

PubMed Central

Schwartz, Jill L.; Rountree, Wes; Kashuba, Angela D. M.; Brache, Vivian; Creinin, Mitchell D.; Poindexter, Alfred; Kearney, Brian P.

2011-01-01

Background Tenofovir (TFV) gel is being evaluated as a microbicide with pericoital and daily regimens. To inhibit viral replication locally, an adequate concentration in the genital tract is critical. Methods and Findings Forty-nine participants entered a two-phase study: single-dose (SD) and multi-dose (MD), were randomized to collection of genital tract samples (endocervical cells [ECC], cervicovaginal aspirate and vaginal biopsies) at one of seven time points [0.5, 1, 2, 4, 6, 8, or 24 hr(s)] post-dose following SD exposure of 4 mL 1% TFV gel and received a single dose. Forty-seven were randomized to once (QD) or twice daily (BID) dosing for 2 weeks and to collection of genital tract samples at 4, 8 or 24 hrs after the final dose, but two discontinued prior to gel application. Blood was collected during both phases at the seven times post-dose. TFV exposure was low in blood plasma for SD and MD; median Cmax was 4.0 and 3.4 ng/mL, respectively (C≤29 ng/mL). TFV concentrations were high in aspirates and tissue after SD and MD, ranging from 1.2×104 to 9.9×106 ng/mL and 2.1×102 to 1.4×106 ng/mL, respectively, and did not noticeably differ between proximal and distal tissue. TFV diphosphate (TFV-DP), the intracellular active metabolite, was high in ECC, ranging from 7.1×103 to 8.8×106 ng/mL. TFV-DP was detectable in approximately 40% of the tissue samples, ranging from 1.8×102 to 3.5×104 ng/mL. AUC for tissue TFV-DP was two logs higher after MD compared to SD, with no noticeable differences when comparing QD and BID. Conclusions Single-dose and multiple-dose TFV gel exposure resulted in high genital tract concentrations for at least 24 hours post-dose with minimal systemic absorption. These results support further study of TFV gel for HIV prevention. Trial registration ClinicalTrials.gov NCT00561496 PMID:22039430

Development of action levels for MED/MPD skin-testing units in ultraviolet phototherapy

NASA Astrophysics Data System (ADS)

O'Connor, Una M.; O'Hare, Neil J.

2003-03-01

Ultraviolet (UV) Phototherapy is commonly used for treatment of skin diseases such as psoriasis and eczema. Treatment is carried out using UV phototherapy units, exposing all or part of the body for a certain exposure time. Prior to exposure in treatment units, an unaffected area of skin may be tested using UV skin-testing units in order to determine a suitable treatment regime. The exposure time at which barely perceptible erythema has developed is known as the Minimal Erythemal Dose (MED) for UVB therapy and Minimal Phototoxic Dose (MPD) for UVA therapy. This is used to determine the starting dose in the treatment regime. The presence of 'hotspots' and 'coldspots' in UV skin-testing units can result in inaccurate determination of MED/MPD. This could give rise to severe burns during treatment, or in a sub-optimal dose regime being used. Quality assurance protocols for UV phototherapy equipment have recently been developed and these protocols have highlighted the need for action levels for skin-testing units. An action level is a reference value, which is used to determine whether the difference in irradiance output level across a UV unit is acceptable. Current methodologies for skin-testing in Ireland have been characterised and errors introduced during testing have been estimated. Action levels have been developed based on analysis of errors and requirements of skin-testing.

Time-course study of different innate immune mediators produced by UV-irradiated skin: comparative effects of short and daily versus a single harmful UV exposure.

PubMed

Cela, Eliana M; Friedrich, Adrian; Paz, Mariela L; Vanzulli, Silvia I; Leoni, Juliana; González Maglio, Daniel H

2015-05-01

The modulatory effects of solar UV radiation on the immune system have been widely studied. As the skin is the main target of UV radiation, our purpose was to compare the impact on skin innate immunity of two contrasting ways to be exposed to sunlight. Hairless mice were UV irradiated with a single high UV dose simulating a harmful exposure, or with repetitive low UV doses simulating short occasional daily exposures. Skin samples were taken at different times after UV irradiation to evaluate skin histology, inflammatory cell recruitment, epidermal T-cell population and the mitochondrial function of epidermal cells. The transcriptional profiles of pro-inflammatory cytokines, chemokines, antimicrobial peptides and Toll-like receptors were evaluated by RT-PCR and ELISA in tissue homogenates. Finally, a lymphangiography was performed to assess modification in the lymphatic vessel system. A single high UV dose produces a deep inflammatory state characterized by the production of pro-inflammatory cytokines and chemokines that, in turn, induces the recruitment of neutrophils and macrophages into the irradiated area. On the other hand, repetitive low UV doses drive the skin to a photo-induced alert state in which there is no sign of inflammation, but the epithelium undergoes changes in thickness, the lymphatic circulation increases, and the transcription of antimicrobial peptides is induced. © 2014 John Wiley & Sons Ltd.

The prolonged gastrointestinal syndrome in rhesus macaques: the relationship between gastrointestinal, hematopoietic, and delayed multi-organ sequelae following acute, potentially lethal, partial-body irradiation.

PubMed

MacVittie, Thomas J; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M

2012-10-01

The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min(-1) to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for efficacy and interaction during the concomitant evolution of acute and delayed key organ-specific subsyndromes.

Dose conversion factors for radon: recent developments.

PubMed

Marsh, James W; Harrison, John D; Laurier, Dominique; Blanchardon, Eric; Paquet, François; Tirmarche, Margot

2010-10-01

Epidemiological studies of the occupational exposure of miners and domestic exposures of the public have provided strong and complementary evidence of the risks of lung cancer following inhalation of radon progeny. Recent miner epidemiological studies, which include low levels of exposure, long duration of follow-up, and good quality of individual exposure data, suggest higher risks of lung cancer per unit exposure than assumed previously by the International Commission on Radiological Protection (ICRP). Although risks can be managed by controlling exposures, dose estimates are required for the control of occupational exposures and are also useful for comparing sources of public exposure. Currently, ICRP calculates doses from radon and its progeny using dose conversion factors from exposure (WLM) to dose (mSv) based on miner epidemiological studies, referred to as the epidemiological approach. Revision of these dose conversion factors using risk estimates based on the most recent epidemiological data gives values that are in good agreement with the results of calculations using ICRP biokinetic and dosimetric models, the dosimetric approach. ICRP now proposes to treat radon progeny in the same way as other radionuclides and to publish dose coefficients calculated using models, for use within the ICRP system of protection.

Emergency Dose Estimation Using Optically Stimulated Luminescence from Human Tooth Enamel

PubMed Central

Sholom, S.; DeWitt, R.; Simon, S.L.; Bouville, A.; McKeever, S.W.S.

2011-01-01

Human teeth were studied for potential use as emergency Optically Stimulated Luminescence (OSL) dosimeters. By using multiple-teeth samples in combination with a custom-built sensitive OSL reader, 60Co-equivalent doses below 0.64 Gy were measured immediately after exposure with the lowest value being 27 mGy for the most sensitive sample. The variability of OSL sensitivity, from individual to individual using multiple-teeth samples, was determined to be 53%. X-ray and beta exposure were found to produce OSL curves with the same shape that differed from those due to ultraviolet (UV) exposure; as a result, correlation was observed between OSL signals after X-ray and beta exposure and was absent if compared to OSL signals after UV exposure. Fading of the OSL signal was “typical” for most teeth with just a few of incisors showing atypical behavior. Typical fading dependences were described by a bi-exponential decay function with “fast” (decay time around of 12 min) and “slow” (decay time about 14 h) components. OSL detection limits, based on the techniques developed to-date, were found to be satisfactory from the point-of-view of medical triage requirements if conducted within 24 hours of the exposure. PMID:21949479

APPLICATION AND USE OF DOSE ESTIMATING EXPOSURE MODEL (DEEM) FOR ROUTE TO ROUTE DOSE COMPARISONS AFTER EXPOSURE TO TRICHLOROETHYLENE (TCE)

EPA Science Inventory

Route-to-route extrapolations are a crucial step in many risk assessments. Often the doses which result In toxicological end points in one route must be compared with doses resulting from typical environmental exposures by another route. In this case we used EPA's Dose Estimati...

Altered gene expression by low-dose arsenic exposure in humans and cultured cardiomyocytes: Assessment by real-time PCR array

EPA Science Inventory

Arsenic contamination in drinking water has become a great public health concern worldwide. Chronic arsenic exposure results in higher risk of skin, lung and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects o...

Identification of fipronil metabolites in rodents by time-of-flight mass spectrometry for application in a human exposure study

EPA Science Inventory

Fipronil is a phenylpyrazole insecticide commonly used in residential and agricultural applications. To understand more about the potential risks associated with fipronil, dosed Long Evans rats were evaluated for metabolites to develop a set of biomarkers for use in human exposur...

A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists

PubMed Central

Miller, Steven L.; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H.; Prager, Eric M.; Almeida-Suhett, Camila P.; Apland, James P.; Braga, Maria F.M.

2015-01-01

Inhibition of acetylcholinesterase (AChE) after nerve agent exposure induces status epilepticus (SE), which causes brain damage or death. The development of countermeasures appropriate for the pediatric population requires testing of anticonvulsant treatments in immature animals. In the present study, exposure of 21-day-old (P21) rats to different doses of soman, followed by probit analysis, produced an LD50 of 62 μg/kg. The onset of behaviorally-observed SE was accompanied by a dramatic decrease in brain AChE activity; rats who did not develop SE had significantly less reduction of AChE activity in the basolateral amygdala than rats who developed SE. Atropine sulfate (ATS) at 2 mg/kg, administered 20 min after soman exposure (1.2XLD50), terminated seizures. ATS at 0.5 mg/kg, given along with an oxime within 1 min after exposure, allowed testing of anticonvulsants at delayed time-points. The AMPA/GluK1 receptor antagonist LY293558, or the specific GluK1 antagonist UBP302, administered 1 h post-exposure, terminated SE. There were no degenerating neurons in soman-exposed P21 rats, but both the amygdala and the hippocampus were smaller than in control rats at 30 and 90 days post-exposure; this pathology was not present in rats treated with LY293558. Behavioral deficits present at 30 days post-exposure, were also prevented by LY293558 treatment. Thus, in immature animals, a single injection of atropine is sufficient to halt nerve agent-induced seizures, if administered timely. Testing anticonvulsants at delayed time-points requires early administration of ATS at a low dose, sufficient to counteract only peripheral toxicity. LY293558 administered 1 h post-exposure, prevents brain pathology and behavioral deficits. PMID:25689173

Low dose trichloroethylene alters cytochrome P450 - 2C subfamily expression in the developing chick heart

PubMed Central

Makwana, Om; Ahles, Lauren; Lencinas, Alejandro; Selmin, Ornella I.; Runyan, Raymond B.

2013-01-01

Trichloroethylene (TCE) is an organic solvent and common environmental contaminant. TCE exposure is associated with heart defects in humans and animal models. Primary metabolism of TCE in adult rodent models is by specific hepatic cytochrome P450 enzymes (Lash et al., 2000). As association of TCE exposure with cardiac defects is in exposed embryos prior to normal liver development, we investigated metabolism of TCE in the early embryo. Developing chick embryos were dosed in ovo with environmentally relevant doses of TCE (8 ppb and 800 ppb) and RNA was extracted from cardiac and extra-cardiac tissue (whole embryo without heart). Real time PCR showed upregulation of CYP2H1 transcripts in response to TCE exposure in the heart. No detectable cytochrome expression was found in extra-cardiac tissue. As seen previously, the dose response was non-monotonic and 8ppb elicited stronger upregulation than 800 ppb. Immunostaining for CYP2C subfamily expression confirmed protein expression and showed localization in both myocardium and endothelium. TCE exposure increased protein expression in both tissues. These data demonstrate that the earliest embryonic expression of phase I detoxification enzymes is in the developing heart. Expression of these CYPs is likely to be relevant to the susceptibility of the developing heart to environmental teratogens. PMID:22855351

Long term effects of radiation exposure on telomere lengths of leukocytes and its associated biomarkers among atomic-bomb survivors.

PubMed

Lustig, Ana; Shterev, Ivo; Geyer, Susan; Shi, Alvin; Hu, Yiqun; Morishita, Yukari; Nagamura, Hiroko; Sasaki, Keiko; Maki, Mayumi; Hayashi, Ikue; Furukawa, Kyoji; Yoshida, Kengo; Kajimura, Junko; Kyoizumi, Seishi; Kusunoki, Yoichiro; Ohishi, Waka; Nakachi, Kei; Weng, Nan-Ping; Hayashi, Tomonori

2016-06-28

Ionizing radiation (IR) is a major source of cellular damage and the immediate cellular response to IR has been well characterized. But the long-term impact of IR on cell function and its relationship with aging are not known. Here, we examined the IR effects on telomere length and other biomarkers 50 to 68 years post-exposure (two time points per person) in survivors of the atomic bombing at Hiroshima during WWII. We found that telomere length of leukocytes was inversely correlated with the dose of IR (p=0.008), and this effect was primarily found in survivors who were exposed at younger ages; specifically those <12 years old (p=0.0004). Although a dose-related retardation of telomere shortening with age was observed in the cross-sectional data, longitudinal follow-up after 11 years did not show IR exposure-related alteration of the rate of telomere shortening with age. In addition, IR diminished the associations between telomere length and selected aging biomarkers that were observed in survivors with no dose. These included uric acid metabolism, cytokines, and blood T cell counts. These findings showed long-lasting detrimental effects of IR on telomere length of leukocytes in both dose- and age-at-exposure dependent manner, and on alterations of biomarkers with aging.

Occupational Ocular UV Exposure in Civilian Aircrew.

PubMed

Chorley, Adrian C; Baczynska, Katarzyna A; Benwell, Martin J; Evans, Bruce J W; Higlett, Michael P; Khazova, Marina; O'Hagan, John B

2016-01-01

Ultraviolet radiation (UVR) increases with altitude; however, there are a number of other factors which may influence ocular exposure during flight. The aim of this study was to assess ocular UVR exposure of pilots in airline and off-shore helicopter operations on different aircraft types and to compare with exposure in a typical office environment. In-flight data were captured on equipment including a CCD array spectroradiometer on five return sector European airline flights and one transatlantic flight from London Gatwick in addition to four helicopter flights from Aberdeen Dyce airport. Further data were collected in an office environment from three workstations during summer and winter months. A wide variation in ocular UVA dose was found during flights. The main factor influencing exposure was the UVR transmission of the windshield, which fell into two distinct profile types. In an aircraft with good UVA blocking properties, ocular exposure was found to be equivalent to office exposure and did not exceed international guideline limits regardless of external conditions or flight time. Most aircraft assessed had poor UVA blocking windshields which resulted in an ocular exposure to the unprotected eye in excess of international guideline limits (up to between 4.5 to 6.5 times greater during one flight). No significant UVB dose was found. Pilots should be warned of the potential high UVA exposure during flight and advised on the use of sunglasses. A windshield labeling system would allow the pilot to tailor their eye protection practices to that particular aircraft.

Patterns of diagnostic imaging and associated radiation exposure among long-term survivors of young adult cancer: a population-based cohort study.

PubMed

Daly, Corinne; Urbach, David R; Stukel, Thérèse A; Nathan, Paul C; Deitel, Wayne; Paszat, Lawrence F; Wilton, Andrew S; Baxter, Nancy N

2015-09-03

Survivors of young adult malignancies are at risk of accumulated exposures to radiation from repetitive diagnostic imaging. We designed a population-based cohort study to describe patterns of diagnostic imaging and cumulative diagnostic radiation exposure among survivors of young adult cancer during a survivorship time period where surveillance imaging is not typically warranted. Young adults aged 20-44 diagnosed with invasive malignancy in Ontario from 1992-1999 who lived at least 5 years from diagnosis were identified using the Ontario Cancer Registry and matched 5 to 1 to randomly selected cancer-free persons. We determined receipt of 5 modalities of diagnostic imaging and associated radiation dose received by survivors and controls from years 5-15 after diagnosis or matched referent date through administrative data. Matched pairs were censored six months prior to evidence of recurrence. 20,911 survivors and 104,524 controls had a median of 13.5 years observation. Survivors received all modalities of diagnostic imaging at significantly higher rates than controls. Survivors received CT at a 3.49-fold higher rate (95% Confidence Interval [CI]:3.37, 3.62) than controls in years 5 to 15 after diagnosis. Survivors received a mean radiation dose of 26 miliSieverts solely from diagnostic imaging in the same time period, a 4.57-fold higher dose than matched controls (95% CI: 4.39, 4.81). Long-term survivors of young adult cancer have a markedly higher rate of diagnostic imaging over time than matched controls, imaging associated with substantial radiation exposure, during a time period when surveillance is not routinely recommended.

Stochastic Human Exposure and Dose Simulation for Air Toxics

EPA Science Inventory

The Stochastic Human Exposure and Dose Simulation model for Air Toxics (SHEDS-AirToxics) is a multimedia, multipathway population-based exposure and dose model for air toxics developed by the US EPA's National Exposure Research Laboratory (NERL). SHEDS-AirToxics uses a probabili...

No effect on QT intervals of mipomersen, a 2'-O-methoxyethyl modified antisense oligonucleotide targeting ApoB-100 mRNA, in a phase I dose escalation placebo-controlled study, and confirmed by a thorough QT (tQT) study, in healthy subjects.

PubMed

Yu, Rosie Z; Gunawan, Rudy; Li, Zhaoyang; Mittleman, Robert S; Mahmood, Asif; Grundy, John S; Singleton, Walter; Geary, Richard; Wang, Yanfeng

2016-03-01

The aim of this study to evaluate the effect of mipomersen on QT intervals in a phase I dose escalation, placebo-controlled study, and a thorough QT (tQT) study in healthy subjects. In the initial phase I study, 29 healthy subjects received either single or multiple (for 4 weeks) ascending doses of mipomersen (50-400 mg) administered subcutaneously (SC) or via a 2-h intravenous (IV) infusion, and 7 subjects received placebo. In the confirmative tQT study, 58 healthy subjects received placebo, 400 mg IV moxifloxacin, 200 mg SC, or 200 mg IV of mipomersen in a double-blind, 4-way crossover design with a minimum 5-day washout between treatments. ECG measurements were performed at baseline and selected time points (including Tmax). The correlation between QTcF intervals corrected for baseline and time-matched placebo when available with PK plasma exposure was evaluated by linear regression analysis. In the phase I study, no positive correlation between the PK exposure and ∆QTcF or ∆∆QTcF was observed within the wide dose or exposure range tested. Similar results were observed in the tQT study, where the predicted ΔΔQTcF and its upper bound of the 90% CI at Cmax of therapeutic and supratherapeutic dose were approximately -1.7 and 2.9 ms, respectively. Mipomersen showed no effect on QT intervals in both the phase I dose escalation study and the tQT study. These results support the proposal that QT assessment can be made in a phase I dose escalation study, and no tQT study may be necessary if the phase I dose escalation study showed a negative QT effect.

BOOK REVIEW: NCRP Report No. 160: Ionizing Radiation Exposure of the Population of the United States NCRP Report No. 160: Ionizing Radiation Exposure of the Population of the United States

NASA Astrophysics Data System (ADS)

Thurston, Jim

2010-10-01

This report by Committee 6 of the Council is an extensive update of a previous report on the exposure of the US population to ionizing radiation sources from data gathered in the 1980s (published as Report 93 in 1987). It is combined with an update on the more in-depth assessment of data on medical exposures previously reported in 1989 (Report 100). Individual chapters in this new report are dedicated to specific sources of exposure to the US population—both from natural and artificial radiation—and the level of detail in each chapter is intended to reflect the significance of the contribution of each source to the total collective dose of the population. The first chapter is on the most significant contributor: background radiation. It expands on the concept of natural background radiation in Report 93, renaming it 'ubiquitous background', and describing in detail the contributions from both extra-terrestrial and terrestrial sources. The data demonstrates that the average dose from such exposure has varied little since the previous report (a slight increase from 3.0 mSv to 3.1 mSv). The next chapter is on medical radiation, i.e. the exposure to the population when attending as patients, not including occupational exposure to hospital workers. The most striking data published in the entire report is the increase in the contribution to the total US population dose attributed to such medical exposures. It is now as significant as that from background radiation: medical exposures now account for an average effective dose to the US citizen of 3.00 mSv, up from 0.53 mSv in 1992 (Report 100). The most important contribution to this increase is the 1.46 mSv from CT scanning alone. The nuclear medicine (including PET) contribution is up from 0.14 mSv to 0.77mSv. This evidently must be due to significant changes in medical radiological practice in the US tied to the increase in the availability of CT and PET imaging facilities. These increasing contributions have driven the overall average effective dose to a US citizen from approximately 3.6 mSv reported in 1987 to 6.2 mSv per annum, with medical exposures now responsible for 48% of the total (up from 15% in 1992). It is interesting to note that over roughly the same period of time, the total dose to the UK population has been revised upwards from 2.6 mSv to 2.7mSv to reflect (amongst other factors) the increase in CT scanning in the UK—obviously a much smaller change. However, one has to consider whether medical radiological practices in the UK might similarly change in the coming years, and UK population doses subsequently follow the US trend reported here. There is now a more detailed chapter on exposure to the population from consumer products and activities. Of the contributing factors in this category, the radiation dose received from radioactivity in tobacco smoke is the most significant, followed by building materials and air travel. There has been no significant change in the total dose received from these sources when compared to the earlier Report 93, at 0.13 mSv. The report also gives significant detail on exposure to the public from industrial sources (not just nuclear power), and discusses occupational exposure. Both these categories of exposure, averaged out of the whole population, give very small contributions to the total dose (0.003 mSv and 0.005 mSv, respectively). There are two final points to make about this report. Firstly, it continues the NCRP policy introduced for Report 93 of using SI units rather than the radiation units more commonly used within the US, hence making this report more readily accessible to an international audience. Secondly, in all the descriptions of the exposures and radiation doses received, no attempt is made to convert the doses into risk. The view of the Council, as stated in the forward to the report, is that attempting to quantify the risks associated with such levels of radiation exposure falls outside the remit of the Committee that prepared the report.

Study on disinfestation of pulses using microwave technique.

PubMed

Singh, Ranjeet; Singh, K K; Kotwaliwale, N

2012-08-01

Mortality of the pulse beetle (Callosobruchus chinensis L.) exposed, continuously, to microwave radiation (2450 MHz) was evaluated as a function of exposure time and percent power level, at adult stages. The microwave exposure time to attain 100% insect mortality at 100 %, 80%, 60%, 40%, and 20% power levels for Chickpea, Pigeon Pea and Green Gram was optimized. Effect of optimized microwave exposure time on viability, germination, cooking and milling characteristics of Chickpea, Pigeon Pea and Green Gram was also evaluated. Adult stage study was characterized by a distinct dose-exposure curve. The mortality curve was following third degree polynomial equation. The seed viability and germination of Chickpea, Pigeon Pea and Green Gram was affected by microwave exposure time and power level. It was observed that as the power level is decreasing the germination and viability of all the pulses are increasing. The effect on cooking and milling characteristics are not affected by microwave exposure time and power level. The insects in the mobile state were observed to move towards the surface from inside the nutrient medium during microwave exposure. They also curled up and in some cases aggregation was observed.

Ionizing radiation: future etiologic research and preventive strategies.

PubMed

Darby, S C; Inskip, P D

1995-11-01

Estimates of cancer risks following exposure to ionizing radiation traditionally have been based on the experience of populations exposed to substantial (and known) doses delivered over short periods of time. Examples include survivors of the atomic bombings at Hiroshima and Nagasaki, and persons treated with radiation for benign or malignant disease. Continued follow-up of these populations is important to determine the long-term effects of exposure in childhood, to characterize temporal patterns of excess risk for different types of cancer, and to understand better the interactions between radiation and other host and environmental factors. Most population exposure to radiation occurs at very low dose rates. For low linear energy transfer (LET) radiations, it often has been assumed that cancer risks per unit dose are lower following protracted exposure than following acute exposure. Studies of nuclear workers chronically exposed over a working lifetime provide data that can be used to test this hypothesis, and preliminary indications are that the risks per unit dose for most cancers other than leukemia are similar to those for acute exposure. However, these results are subject to considerable uncertainty, and further information on this question is needed. Residential radon is the major source of population exposure to high-LET radiation. Current estimates of the risk of lung cancer due to residential exposure to radon and radon daughters are based on the experience of miners exposed to much higher concentrations. Data indicate that lung cancer risk among miners is inversely associated with exposure rate, and also is influenced by the presence of other lung carcinogens such as arsenic in the mine environment. Further study of populations of radon-exposed miners would be informative, particularly those exposed at below-average levels. More direct evidence on the effects of residential exposure to radon also is desirable but might be difficult to come by, as risks associated with radon levels found in most homes might be too low to be quantified accurately in epidemiological studies.

Ionizing radiation: future etiologic research and preventive strategies.

PubMed Central

Darby, S C; Inskip, P D

1995-01-01

Estimates of cancer risks following exposure to ionizing radiation traditionally have been based on the experience of populations exposed to substantial (and known) doses delivered over short periods of time. Examples include survivors of the atomic bombings at Hiroshima and Nagasaki, and persons treated with radiation for benign or malignant disease. Continued follow-up of these populations is important to determine the long-term effects of exposure in childhood, to characterize temporal patterns of excess risk for different types of cancer, and to understand better the interactions between radiation and other host and environmental factors. Most population exposure to radiation occurs at very low dose rates. For low linear energy transfer (LET) radiations, it often has been assumed that cancer risks per unit dose are lower following protracted exposure than following acute exposure. Studies of nuclear workers chronically exposed over a working lifetime provide data that can be used to test this hypothesis, and preliminary indications are that the risks per unit dose for most cancers other than leukemia are similar to those for acute exposure. However, these results are subject to considerable uncertainty, and further information on this question is needed. Residential radon is the major source of population exposure to high-LET radiation. Current estimates of the risk of lung cancer due to residential exposure to radon and radon daughters are based on the experience of miners exposed to much higher concentrations. Data indicate that lung cancer risk among miners is inversely associated with exposure rate, and also is influenced by the presence of other lung carcinogens such as arsenic in the mine environment. Further study of populations of radon-exposed miners would be informative, particularly those exposed at below-average levels. More direct evidence on the effects of residential exposure to radon also is desirable but might be difficult to come by, as risks associated with radon levels found in most homes might be too low to be quantified accurately in epidemiological studies. PMID:8741792

Ladtap XL Version 2017: A Spreadsheet For Estimating Dose Resulting From Aqueous Releases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minter, K.; Jannik, T.

LADTAP XL© is an EXCEL© spreadsheet used to estimate dose to offsite individuals and populations resulting from routine and accidental releases of radioactive materials to the Savannah River. LADTAP XL© contains two worksheets: LADTAP and IRRIDOSE. The LADTAP worksheet estimates dose for environmental pathways including external exposure resulting from recreational activities on the Savannah River and internal exposure resulting from ingestion of water, fish, and invertebrates originating from the Savannah River. IRRIDOSE estimates offsite dose to individuals and populations from irrigation of foodstuffs with contaminated water from the Savannah River. In 2004, a complete description of the LADTAP XL© codemore » and an associated user’s manual was documented in LADTAP XL©: A Spreadsheet for Estimating Dose Resulting from Aqueous Release (WSRC-TR-2004-00059) and revised input parameters, dose coefficients, and radionuclide decay constants were incorporated into LADTAP XL© Version 2013 (SRNL-STI-2011-00238). LADTAP XL© Version 2017 is a slight modification to Version 2013 with minor changes made for more user-friendly parameter inputs and organization, updates in the time conversion factors used within the dose calculations, and fixed an issue with the expected time build-up parameter referenced within the population shoreline dose calculations. This manual has been produced to update the code description, verification of the models, and provide an updated user’s manual. LADTAP XL© Version 2017 has been verified by Minter (2017) and is ready for use at the Savannah River Site (SRS).« less

The effect of food on the pharmacokinetics of oral ibrutinib in healthy participants and patients with chronic lymphocytic leukemia.

PubMed

de Jong, Jan; Sukbuntherng, Juthamas; Skee, Donna; Murphy, Joe; O'Brien, Susan; Byrd, John C; James, Danelle; Hellemans, Peter; Loury, David J; Jiao, Juhui; Chauhan, Vijay; Mannaert, Erik

2015-05-01

To assess ibrutinib pharmacokinetics under fasted and fed conditions, impact of food-intake timing, and the safety and tolerability. Three studies were analyzed. Study 1 was a randomized, open-label, single-dose, four-way crossover study in 44 healthy participants. Study 2 was a randomized, repeat-dose crossover study in 16 patients with previously treated chronic lymphocytic leukemia (CLL). Ibrutinib dose was 420 mg in both studies. Study 3 was an open-label, sequential study to assess the effect of a standard breakfast on ibrutinib 560 mg in eight healthy participants. Administration of single-dose ibrutinib under fasting conditions (study 1) resulted in approximately 60 % of exposure compared with drug intake either 30 min before, 30 min after (fed), or 2 h after a high-fat meal. Similar food effect was observed (study 3) when ibrutinib was given 30 min before meal. In CLL patients (study 2), the C max and AUC under fasting conditions were 43 and 61 %, respectively, relative to fed conditions. When administered once-daily in uncontrolled food-intake conditions (≥30 min before or 2 h after), exposures were slightly (≈30 %) lower than in fed condition. When corrected for repeated dosing, pharmacokinetic parameters in healthy participants and patients were comparable. Ibrutinib was generally well tolerated in all settings studied. Ibrutinib administered in fasted condition reduces exposure to approximately 60 % as compared with dosing in proximity to food-intake, regardless of timing/type of meal. Because repeated drug intake in fasted condition is unlikely, no food restrictions may be needed to administer ibrutinib.

Acute radiation syndrome: assessment and management.

PubMed

Donnelly, Elizabeth H; Nemhauser, Jeffrey B; Smith, James M; Kazzi, Ziad N; Farfán, Eduardo B; Chang, Arthur S; Naeem, Syed F

2010-06-01

Primary care physicians may be unprepared to diagnose and treat rare, yet potentially fatal, illnesses such as acute radiation syndrome (ARS). ARS, also known as radiation sickness, is caused by exposure to a high dose of penetrating, ionizing radiation over a short period of time. The time to onset of ARS is dependent on the dose received, but even at the lowest doses capable of causing illness, this will occur within a matter of hours to days. This article describes the clinical manifestations of ARS, provides guidelines for assessing its severity, and makes recommendations for managing ARS victims.

Elevated Radiation Exposure Associated With Above Surface Flat Detector Mini C-Arm Use.

PubMed

Martin, Dennis P; Chapman, Talia; Williamson, Christopher; Tinsley, Brian; Ilyas, Asif M; Wang, Mark L

2017-11-01

This study aims to test the hypothesis that: (1) radiation exposure is increased with the intended use of Flat Surface Image Intensifier (FSII) units above the operative surface compared with the traditional below-table configuration; (2) this differential increases in a dose-dependent manner; and (3) radiation exposure varies with body part and proximity to the radiation source. A surgeon mannequin was seated at a radiolucent hand table, positioned for volar distal radius plating. Thermoluminescent dosimeters measured exposure to the eyes, thyroid, chest, hand, and groin, for 1- and 15-minute trials from a mini C-arm FSII unit positioned above and below the operating surface. Background radiation was measured by control dosimeters placed within the operating theater. At 1-minute of exposure, hand and eye dosages were significantly greater with the flat detector positioned above the table. At 15-minutes of exposure, hand radiation dosage exceeded that of all other anatomic sites with the FSII in both positions. Hand exposure was increased in a dose-dependent manner with the flat detector in either position, whereas groin exposure saw a dose-dependent only with the flat detector beneath the operating table. These findings suggest that the surgeon's hands and eyes may incur greater radiation exposure compared with other body parts, during routine mini C-arm FSII utilization in its intended position above the operating table. The clinical impact of these findings remains unclear, and future long-term radiation safety investigation is warranted. Surgeons should take precautions to protect critical body parts, particularly when using FSII technology above the operating with prolonged exposure time.

Automatic exposure control at single- and dual-heartbeat CTCA on a 320-MDCT volume scanner: effect of heart rate, exposure phase window setting, and reconstruction algorithm.

PubMed

Funama, Yoshinori; Utsunomiya, Daisuke; Taguchi, Katsuyuki; Oda, Seitaro; Shimonobo, Toshiaki; Yamashita, Yasuyuki

2014-05-01

To investigate whether electrocardiogram (ECG)-gated single- and dual-heartbeat computed tomography coronary angiography (CTCA) with automatic exposure control (AEC) yields images with uniform image noise at reduced radiation doses. Using an anthropomorphic chest CT phantom we performed prospectively ECG-gated single- and dual-heartbeat CTCA on a second-generation 320-multidetector CT volume scanner. The exposure phase window was set at 75%, 70-80%, 40-80%, and 0-100% and the heart rate at 60 or 80 or corr80 bpm; images were reconstructed with filtered back projection (FBP) or iterative reconstruction (IR, adaptive iterative dose reduction 3D). We applied AEC and set the image noise level to 20 or 25 HU. For each technique we determined the image noise and the radiation dose to the phantom center. With half-scan reconstruction at 60 bpm, a 70-80% phase window- and a 20-HU standard deviation (SD) setting, the imagenoise level and -variation along the z axis manifested similar curves with FBP and IR. With half-scan reconstruction, the radiation dose to the phantom center with 70-80% phase window was 18.89 and 12.34 mGy for FBP and 4.61 and 3.10 mGy for IR at an SD setting SD of 20 and 25 HU, respectively. At 80 bpm with two-segment reconstruction the dose was approximately twice that of 60 bpm at both SD settings. However, increasing radiation dose at corr80 bpm was suppressed to 1.39 times compared to 60 bpm. AEC at ECG-gated single- and dual-heartbeat CTCA controls the image noise at different radiation dose. Copyright © 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Comparative effects of pulmonary and parenteral Δ⁹-tetrahydrocannabinol exposure on extinction of opiate-induced conditioned aversion in rats.

PubMed

Manwell, Laurie A; Mallet, Paul E

2015-05-01

Evidence suggesting that the endogenous cannabinoid (eCB) system can be manipulated to facilitate or impair extinction of learned behaviours has important consequences for opiate withdrawal and abstinence. We demonstrated that the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases eCB levels, facilitates extinction of a naloxone-precipitated morphine withdrawal-induced conditioned place aversion (CPA). The potential of the exogenous CB1 ligand, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), to facilitate extinction of this CPA was tested. Effects of both pulmonary and parenteral Δ(9)-THC exposure were evaluated using comparable doses previously determined. Rats trained to associate a naloxone-precipitated morphine withdrawal with a floor cue were administered Δ(9)-THC-pulmonary (1, 5, 10 mg vapour inhalation) or parenteral (0.5, 1.0, 1.5 mg/kg intraperitoneal injection)-prior to each of 20 to 28 extinction/testing trials. Vapourized Δ(9)-THC facilitated extinction of the CPA in a dose- and time-dependent manner: 5 and 10 mg facilitated extinction compared to vehicle and 1 mg Δ(9)-THC. Injected Δ(9)-THC significantly impaired extinction only for the 1.0-mg/kg dose: it prolonged the CPA fourfold longer than the vehicle and 0.5- and 1.5-mg/kg doses. These data suggest that both dose and route of Δ(9)-THC administration have important consequences for its pharmacokinetic and behavioural effects; specifically, pulmonary exposure at higher doses facilitates, whereas pulmonary and parenteral exposure at lower doses impairs, rates of extinction learning for CPA. Pulmonary-administered Δ(9)-THC may prove beneficial for potentiation of extinction learning for aversive memories, such as those supporting drug-craving/seeking in opiate withdrawal syndrome, and other causes of conditioned aversions, such as illness and stress.

The individual tolerance concept is not the sole explanation for the probit dose-effect model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Newman, M.C.; McCloskey, J.T.

2000-02-01

Predominant methods for analyzing dose- or concentration-effect data (i.e., probit analysis) are based on the concept of individual tolerance or individual effective dose (IED, the smallest characteristic dose needed to kill an individual). An alternative explanation (stochasticity hypothesis) is that individuals do not have unique tolerances: death results from stochastic processes occurring similarly in all individuals. These opposing hypotheses were tested with two types of experiments. First, time to stupefaction (TTS) was measured for zebra fish (Brachydanio rerio) exposed to benzocaine. The same 40 fish were exposed during five trials to test if the same order for TTS was maintainedmore » among trials. The IED hypothesis was supported with a minor stochastic component being present. Second, eastern mosquitofish (Gambusia holbrooki) were exposed to sublethal or lethal NaCl concentrations until a large portion of the lethally exposed fish died. After sufficient time for recovery, fish sublethally exposed and fish surviving lethal exposure were exposed simultaneously to lethal NaCl concentrations. No statistically significant effect was found of previous exposure on survival time but a large stochastic component to the survival dynamics was obvious. Repetition of this second type of test with pentachlorophenol also provided no support for the IED hypothesis. The authors conclude that neither hypothesis alone was the sole or dominant explanation for the lognormal (probit) model. Determination of the correct explanation (IED or stochastic) or the relative contributions of each is crucial to predicting consequences to populations after repeated or chronic exposures to any particular toxicant.« less

Inhalational and dermal exposures during spray application of biocides.

PubMed

Berger-Preiss, Edith; Boehncke, Andrea; Könnecker, Gustav; Mangelsdorf, Inge; Holthenrich, Dagmar; Koch, Wolfgang

2005-01-01

Data on inhalational and potential dermal exposures during spray application of liquid biocidal products were generated. On the one hand, model experiments with different spraying devices using fluorescent tracers were carried out to investigate the influence of parameters relevant to the exposure (e.g. spraying equipment, nozzle size, direction of application). On the other hand, measurements were performed at selected workplaces (during disinfection operations in food and feed areas; pest control operations for private, public and veterinary hygiene; wood protection and antifouling applications) after application of biocidal products such as Empire 20, Responsar SC, Omexan-forte, Actellic, Perma-forte; Fendona SC, Pyrethrum mist; CBM 8, Aldekol Des 03, TAD CID, Basileum, Basilit. The measurements taken in the model rooms demonstrated dependence of the inhalation exposure on the type of spraying device used, in the following order: "spraying with low pressure" < "airless spraying" < "fogging" indicating that the particle diameter of the released spray droplets is the most important parameter. In addition inhalation exposure was lowest when the spraying direction was downward. Also for the potential dermal exposure, the spraying direction was of particular importance: overhead spraying caused the highest contamination of body surfaces. The data of inhalational and potential dermal exposures gained through workplace measurements showed considerable variation. During spraying procedures with low-pressure equipments, dose rates of active substances inhaled by the operators ranged from 7 to 230 microg active substance (a.s.)/h. An increase in inhaled dose rates (6-33 mg a.s./h) was observed after use of high application volumes/time unit during wood protection applications indoors. Spraying in the veterinary sector using medium-pressure sprayers led to inhaled dose rates between 2 and 24mga.s./h. The highest inhaled dose rates were measured during fogging (114 mg a.s./h) and after-high-pressure applications in the antifouling sector (110-300 mg a.s./h). The potential dermal exposure of spray operators was lowest (dose rates from 0.2 to 7 mg a.s./h) in the areas of food and feed disinfection and private and public hygiene during spraying with low-pressure devices. During fogging, wood protection and antifouling applications, high-potential dermal exposures of the operators were determined. Dermal dose rates varied between 100 and 34,000 mg a.s./h.

ASSESSMENT OF VISUAL FUNCTION AND RETINAL STRUCTURE FOLLOWING ACUTE LIGHT EXPOSURE IN THE LIGHT SENSITIVE T4R RHODOPSIN MUTANT DOG

PubMed Central

Iwabe, Simone; Ying, Gui-Shuang; Aguirre, Gustavo D.; Beltran, William A.

2016-01-01

The effect of acute exposure to various intensities of white light on visual behavior and retinal structure was evaluated in the T4R RHO dog, a naturally-occurring model of autosomal dominant retinitis pigmentosa due to a mutation in the Rhodopsin gene. A total of 14 dogs (ages: 4–5.5 months) were used in this study: 3 homozygous mutant RHOT4R/T4R, 8 heterozygous mutant RHOT4R/+, and 3 normal wild-type (WT) dogs. Following overnight dark adaptation, the left eyes were acutely exposed to bright white light with a monocular Ganzfeld dome, while the contralateral right eye was shielded. Each of the 3 homozygous (RHOT4R/T4R) mutant dogs had a single unilateral light exposure (LE) to a different (low, moderate, and high) dose of white light (corneal irradiance/illuminance: 0.1 mW/cm2, 170 lux; 0.5 mW/cm2, 820 lux; or 1 mW/cm2, 1590 lux) for 1min. All 8 heterozygous (RHOT4R/+) mutant dogs were exposed once to the same moderate dose of light. The 3 WT dogs had their left eyes exposed 1, 2, or 3 times to the same highest dose of light. Visual function prior to LE and at 2 weeks and 33 weeks after exposure was objectively assessed in the RHOT4R/T4R and WT dogs by using an obstacle-avoidance course. Transit time through the obstacle course was measured under different scotopic to photopic ambient illuminations. Morphological retinal changes were evaluated by non-invasive in vivo cSLO/sdOCT imaging and histology before and at several time-points (2–36 weeks) after light exposure. The analysis of the transit time through the obstacle course showed that no differences were observed in any of mutant or WT dogs at 2 weeks and 33 weeks post LE. The RHOT4R/T4R retina exposed to the lowest dose of white light showed no obvious changes in ONL thickness at 2 weeks, but mild decrease was noted 36 weeks after LE. The RHOT4R/T4R retina that received a moderate dose (showed an obvious decrease in ONL thickness along the superior and temporal meridians at 2 weeks post LE with more severe damage at 36 weeks post LE in all four meridians. The RHOT4R/T4R retina exposed to the high dose showed at 2 weeks after LE extensive ONL damage in all four meridians. This light intensity did not cause any retinal damage in WT dogs even after repeated (up to 3) LE. Analysis of ONL thickness in heterozygous mutant dogs exposed to the moderate dose of light confirmed the increased sensitivity to light damage of the superior/tapetal retina, and the occurrence of an ongoing cell death process several weeks after the acute LE. In conclusion, a short single exposure to a dose of white light that is not retinotoxic in WT dogs causes in the T4R RHO retina an acute loss of ONL in the central to mid peripheral region that keeps progressing over the course of several weeks. However, this severe retinal damage does not affect visual behavior presumably because of islands of surviving photoreceptors found in the area centralis including the newly discovered canine fovea-like area, and the lack of damage to peripheral photoreceptors. PMID:27085210

Induction and repair of HZE induced cytogenetic damage

NASA Technical Reports Server (NTRS)

Brooks, A. L.; Bao, S.; Rithidech, K.; Chrisler, W. B.; Couch, L. A.; Braby, L. A.

2001-01-01

Wistar rats were exposed to high-mass, high energy (HZE) 56Fe particles (1000 GeV/AMU) using the Alternating Gradient Synchrotron (AGS). The animals were sacrificed at 1-5 hours or after a 30-day recovery period. The frequency of micronuclei in the tracheal and the deep lung epithelial cells were evaluated. The relative effectiveness of 56Fe, for the induction of initial chromosome damage in the form of micronuclei, was compared to damage produced in the same biological system exposed to other types of high and low-LET radiation. It was demonstrated that for animals sacrificed at short times after exposure, the tracheal and lung epithelial cells, the 56Fe particles were 3.3 and 1.3 times as effective as 60Co in production of micronuclei, respectively. The effectiveness was also compared to that for exposure to inhaled radon. With this comparison, the 56Fe exposure of the tracheal epithelial cells and the lung epithelial cells were only 0.18 and 0.20 times as effective as radon in the production of the initial cytogenetic damage. It was suggested that the low relative effectiveness was related to potential for 'wasted energy' from the core of the 56Fe particles. When the animals were sacrificed after 30 days, the slopes of the dose-response relationships, which reflect the remaining level of damage, decreased by a factor of 10 for both the tracheal and lung epithelial cells. In both cases, the slope of the dose-response lines were no longer significantly different from zero, and the r2 values were very high. Lung epithelial cells, isolated from the animals sacrificed hours after exposure, were maintained in culture, and the micronuclei frequency evaluated after 4 and 6 subcultures. These cells were harvested at 24 and 36 days after the exposure. There was no dose-response detected in these cultures and no signs of genomic instability at either sample time.

A practical method to standardise and optimise the Philips DoseRight 2.0 CT automatic exposure control system.

PubMed

Wood, T J; Moore, C S; Stephens, A; Saunderson, J R; Beavis, A W

2015-09-01

Given the increasing use of computed tomography (CT) in the UK over the last 30 years, it is essential to ensure that all imaging protocols are optimised to keep radiation doses as low as reasonably practicable, consistent with the intended clinical task. However, the complexity of modern CT equipment can make this task difficult to achieve in practice. Recent results of local patient dose audits have shown discrepancies between two Philips CT scanners that use the DoseRight 2.0 automatic exposure control (AEC) system in the 'automatic' mode of operation. The use of this system can result in drifting dose and image quality performance over time as it is designed to evolve based on operator technique. The purpose of this study was to develop a practical technique for configuring examination protocols on four CT scanners that use the DoseRight 2.0 AEC system in the 'manual' mode of operation. This method used a uniform phantom to generate reference images which form the basis for how the AEC system calculates exposure factors for any given patient. The results of this study have demonstrated excellent agreement in the configuration of the CT scanners in terms of average patient dose and image quality when using this technique. This work highlights the importance of CT protocol harmonisation in a modern Radiology department to ensure both consistent image quality and radiation dose. Following this study, the average radiation dose for a range of CT examinations has been reduced without any negative impact on clinical image quality.

Impact of intense x-ray pulses on a NaI(Tl)-based gamma camera

NASA Astrophysics Data System (ADS)

Koppert, W. J. C.; van der Velden, S.; Steenbergen, J. H. L.; de Jong, H. W. A. M.

2018-03-01

In SPECT/CT systems x-ray and γ-ray imaging is performed sequentially. Simultaneous acquisition may have advantages, for instance in interventional settings. However, this may expose a gamma camera to relatively high x-ray doses and deteriorate its functioning. We studied the NaI(Tl) response to x-ray pulses with a photodiode, PMT and gamma camera, respectively. First, we exposed a NaI(Tl)-photodiode assembly to x-ray pulses to investigate potential crystal afterglow. Next, we exposed a NaI(Tl)-PMT assembly to 10 ms LED pulses (mimicking x-ray pulses) and measured the response to flashing LED probe-pulses (mimicking γ-pulses). We then exposed the assembly to x-ray pulses, with detector entrance doses of up to 9 nGy/pulse, and analysed the response for γ-pulse variations. Finally, we studied the response of a Siemens Diacam gamma camera to γ-rays while exposed to x-ray pulses. X-ray exposure of the crystal, read out with a photodiode, revealed 15% afterglow fraction after 3 ms. The NaI(Tl)-PMT assembly showed disturbances up to 10 ms after 10 ms LED exposure. After x-ray exposure however, responses showed elevated baselines, with 60 ms decay-time. Both for x-ray and LED exposure and after baseline subtraction, probe-pulse analysis revealed disturbed pulse height measurements shortly after exposure. X-ray exposure of the Diacam corroborated the elementary experiments. Up to 50 ms after an x-ray pulse, no events are registered, followed by apparent energy elevations up to 100 ms after exposure. Limiting the dose to 0.02 nGy/pulse prevents detrimental effects. Conventional gamma cameras exhibit substantial dead-time and mis-registration of photon energies up to 100 ms after intense x-ray pulses. This is due PMT limitations and due to afterglow in the crystal. Using PMTs with modified circuitry, we show that deteriorative afterglow effects can be reduced without noticeable effects on the PMT performance, up to x-ray pulse doses of 1 nGy.

Inflammation-associated gene expression in RAW 264.7 macrophages induced by toxins from fungi common on damp building materials.

PubMed

Rand, Thomas G; Chang, Carolyn T; McMullin, David R; Miller, J David

2017-09-01

Most fungi that grow on damp building materials produce low molecular weight compounds, some of which are known to be toxic. In this study, we tested the hypothesis that exposure to some metabolites of fungi common on damp building materials would result in time-, dose-, and compound-specific responses in the production of various chemokines by RAW 264.7 cells. Cell cultures were exposed to a 10 -7 M or 10 -8 M metabolite dose for 2, 4, 8 or 24h. Metabolite concentrations used were based on those that might be expected in alveolar macrophages due to inhalation exposure from living or working in a damp building. Compared to controls, exposure provoked significant time-, dose- and compound-specific responses manifest as differentially elevated secretion of three of nine cytokines tested in culture supernatant of treated cells. The greatest number of cytokines produced in response to the metabolites tested were in andrastin A-treated cells (GM-CSF, TGFβ1, Tnf-α) followed by koninginin A (TGFβ1 and Tnf-α) and phomenone (GM-CSF, TGFβ1). Chaetoglobosin A, chaetomugilin D and walleminone exposures each resulted in significant time-specific production of Tnf-α only. This investigation adds to a body of evidence supporting the role of low molecular weight compounds from damp building materials as pathogen associated molecular patterns (PAMPs). Along with fungal glucan and chitin, these compounds contribute to the non-allergy based respiratory outcomes for people living and working in damp buildings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxidative damage mediated iNOS and UCP-2 upregulation in rat brain after sub-acute cyanide exposure: dose and time-dependent effects.

PubMed

Bhattacharya, Rahul; Singh, Poonam; John, Jebin Jacob; Gujar, Niranjan L

2018-04-03

Cyanide-induced chemical hypoxia is responsible for pronounced oxidative damage in the central nervous system. The disruption of mitochondrial oxidative metabolism has been associated with upregulation of uncoupling proteins (UCPs). The present study addresses the dose- and time-dependent effect of sub-acute cyanide exposure on various non-enzymatic and enzymatic oxidative stress markers and their correlation with inducible-nitric oxide synthase (iNOS) and uncoupling protein-2 (UCP-2) expression. Animals received (oral) triple distilled water (vehicle control), 0.25 LD50 potassium cyanide (KCN) or 0.50 LD50 KCN daily for 21 d. Animals were sacrificed on 7, 14 and 21 d post-exposure to measure serum cyanide and nitrite, and brain malondialdehyde (MDA), reduced glutathione (GSH), glutathione disulfide (GSSG), cytochrome c oxidase (CCO), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CA) levels, together with iNOS and UCP-2 expression, and DNA damage. The study revealed that a dose- and time-dependent increase in cyanide concentration was accompanied by corresponding CCO inhibition and elevated MDA levels. Decrease in GSH levels was not followed by reciprocal change in GSSG levels. Diminution of SOD, GPx, GR and CA activity was congruent with elevated nitrite levels and upregulation of iNOS and UCP-2 expression, without any DNA damage. It was concluded that long-term cyanide exposure caused oxidative stress, accompanied by upregulation of iNOS. The upregulation of UCP-2 further sensitized the cells to cyanide and accentuated the oxidative stress, which was independent of DNA damage.

Time-Course of the Ethanol-like Discriminative Stimulus Effects of Abused Inhalants in Mice

PubMed Central

Bowen, Scott E.

2009-01-01

Abused solvents have effects similar to those of abused depressant drugs. This experiment evaluated the time course of the discriminative stimulus effects of toluene and 1,1,1-trichloroethane (TRI). Mice were trained to discriminate between i.p. injections of ethanol (EtOH;1.25 g/kg) and saline in a two-lever operant task in which responding was under the control of a fixed-ratio 20 schedule. After 20-min inhalation exposures to toluene (500–6000 ppm) or TRI (1,000–12,000 ppm), stimulus generalization was examined at 0, 5, 10, 20, and 40 min post-exposure. Ethanol doses ≥ 0.25 g/kg produced increases in EtOH-lever responding with full substitution occurring immediately after testing for doses between 1.25 and 2.5 g/kg. Toluene and TRI produced increased EtOH-lever responding at 0–10 min post exposure with some EtOH-lever responding occurring up to 20-min post exposure. Response rates were not decreased for any concentration of toluene or TRI immediately following inhalant exposure but several concentrations elevated rates from 5–40 min post exposure. These results confirm and extend previous studies and show these solvents produce similar effects in EtOH-lever responding but with potency differences. The time-dependent differences in EtOH-lever responding suggest that as solvents are cleared from the body, the EtOH-like subjective effects also fade. PMID:18722399

Levels of ambient air pollution according to mode of transport: a systematic review.

PubMed

Cepeda, Magda; Schoufour, Josje; Freak-Poli, Rosanne; Koolhaas, Chantal M; Dhana, Klodian; Bramer, Wichor M; Franco, Oscar H

2017-01-01

Controversy exists about the differences in air pollution exposure and inhalation dose between mode of transport. We aimed to review air pollution exposure and inhaled dose according to mode of transport and pollutant and their effect in terms of years of life expectancy (YLE). In this systematic review, we searched ten online databases from inception to April 13, 2016, without language or temporal restrictions, for cohort, cross-sectional, and experimental studies that compared exposure to carbon monoxide, black carbon, nitrogen dioxide, and fine and coarse particles in active commuters (pedestrian or cyclist) and commuters using motorised transport (car, motorcycle, bus, or massive motorised transport [MMT-ie, train, subway, or metro]). We excluded studies that measured air pollution exposure exclusively with biomarkers or on the basis of simulated data, reviews, comments, consensuses, editorials, guidelines, in-vitro studies, meta-analyses, ecological studies, and protocols. We extracted average exposure and commuting time per mode of transport and pollutant to calculate inhaled doses. We calculated exposure and inhaled dose ratios using active commuters as the reference and summarised them with medians and IQRs. We also calculated differences in YLE due to fine particle inhaled dose and physical activity. We identified 4037 studies, of which 39 were included in the systematic review. Overall, car commuters had higher exposure to all pollutants than did active commuters in 30 (71%) of 42 comparisons (median ratio 1·22 [IQR 0·90-1·76]), followed by those who commuted by bus in 57 (52%) of 109 (1·0 [0·79-1·41]), by motorcycle in 16 (50%) of 32 (0·99 [0·86-1·38]), by a car with controlled ventilation settings in 39 (45%) of 86 (0·95 [0·66-1·54]), and by MMT in 21 (38%) of 55 (0·67 [0·49-1·13]). Overall, active commuters had higher inhalation doses than did commuters using motorised transport (median ratio car with controlled ventilation settings 0·16 [0·10-0·28]; car 0·22 [0·15-0·30]; motorcycle 0·38 [0·26-0·78]; MMT 0·49 [0·34-0·81]; bus 0·72 [IQR 0·50-0·99]). Commuters using motorised transport lost up to 1 year in YLE more than did cyclists. Proximity to traffic and high air interchange increased the exposure to air pollution of commuters using motorised transport. Larger inhalation rates and commuting time increased inhaled dose among active commuters. Benefits of active commuting from physical activity are larger than the risk from an increased inhaled dose of fine particles. Departamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCIAS), National Health and Medical Research Council, Nestlé Nutrition (Nestec), Metagenics, and AXA. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.

Microdosemeter instrument (MIDN) for assessing risk in space.

PubMed

Pisacane, V L; Dolecek, Q E; Malak, H; Cucinotta, F A; Zaider, M; Rosenfeld, A B; Rusek, A; Sivertz, M; Dicello, J F

2011-02-01

Radiation in space generally produces higher dose rates than that on the Earth's surface, and contributions from primary galactic and solar events increase with altitude within the magnetosphere. Presently, no personnel monitor is available to astronauts for real-time monitoring of dose, radiation quality and regulatory risk. This group is developing a prototypic instrument for use in an unknown, time-varying radiation field. This microdosemeter-dosemeter nucleon instrument is for use in a spacesuit, spacecraft, remote rover and other applications. It provides absorbed dose, dose rate and dose equivalent in real time so that action can be taken to reduce exposure. Such a system has applications in health physics, anti-terrorism and radiation-hardening of electronics as well. The space system is described and results of ground-based studies are presented and compared with predictions of transport codes. An early prototype in 2007 was successfully launched, the only solid-state microdosemeter to have flown in space.

Occupational and patient exposure in coronary angiography procedures

NASA Astrophysics Data System (ADS)

Sulieman, A.; Alzimami, K.; Gafar, R.; Babikir, E.; Alsafi, K.; Suliman, I. I.

2014-11-01

Cardiac catheterization is the gold standard in the diagnosis and management of coronary artery diseases. The objectives of this study were to evaluate the radiation dose of patients and staff during cardiology procedures. Staff was monitored using thermoluminescence dosimeter (TLD) chips for 86 procedures. The mean patient dose was 2813.6 μGy m2 and the mean fluoroscopic time was 4.8 min. The mean radiation doses for cardiologists were 0.9 mGy for the forehead, 0.92 mGy for the thyroid, 1.38 mGy for the chest, 1.28 mGy for the waist and 1.41 mGy for the hand. The mean radiation doses for assistants were 0.72 mGy for the chest, 0.82 mGy for the hand. High patient and staff exposure is due to lack of experience and protective equipment, exacerbated by a high workload. Interventional procedures remain operator dependent; therefore, continuous training is crucial.

A priming dose of protons alters the early cardiac cellular and molecular response to 56Fe irradiation

NASA Astrophysics Data System (ADS)

Ramadan, Samy S.; Sridharan, Vijayalakshmi; Koturbash, Igor; Miousse, Isabelle R.; Hauer-Jensen, Martin; Nelson, Gregory A.; Boerma, Marjan

2016-02-01

Purpose: Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a ;priming; dose of protons on the cardiac cellular and molecular response to a ;challenge; dose of 56Fe in a mouse model. Methods: Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of 56Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of 56Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death. Results: Exposure to 56Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before 56Fe prevented all of the responses to 56Fe. Conclusions: This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions.

A priming dose of protons alters the early cardiac cellular and molecular response to (56)Fe irradiation.

PubMed

Ramadan, Samy S; Sridharan, Vijayalakshmi; Koturbash, Igor; Miousse, Isabelle R; Hauer-Jensen, Martin; Nelson, Gregory A; Boerma, Marjan

2016-02-01

Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a "priming" dose of protons on the cardiac cellular and molecular response to a "challenge" dose of (56)Fe in a mouse model. Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of (56)Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of (56)Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death. Exposure to (56)Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before (56)Fe prevented all of the responses to (56)Fe. This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions. Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

A priming dose of protons alters the early cardiac cellular and molecular response to 56Fe irradiation

PubMed Central

Ramadan, Samy S.; Sridharan, Vijayalakshmi; Koturbash, Igor; Miousse, Isabelle R.; Hauer-Jensen, Martin; Nelson, Gregory A.; Boerma, Marjan

2015-01-01

Purpose Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a “priming” dose of protons on the cardiac cellular and molecular response to a “challenge” dose of 56Fe in a mouse model. Methods Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of 56Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of 56Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death. Results Exposure to 56Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before 56Fe prevented all of the responses to 56Fe. Conclusions This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions. PMID:26948008

Differentiating Nonoccupational Postexposure Prophylaxis Seroconverters and Non-Seroconverters in a Community-Based Clinic in Los Angeles, California

PubMed Central

Weiss, Robert E.; Bolan, Robert K.; Kofron, Ryan M.; Flynn, Risa P.; Pieribone, David L.; Kulkarni, Sonali P.; Landovitz, Raphael J.

2017-01-01

Abstract Background. Nonoccupational postexposure prophylaxis (nPEP) is a 28-day regimen of antiretroviral medications taken within 72 hours of human immunodeficiency virus (HIV) exposure to prevent HIV acquisition. Although nPEP has been recommended since 1998, few studies have analyzed the characteristics that distinguish nPEP failures (seroconverters) and successes (non-seroconverters). Methods. This retrospective study analyzed all nPEP courses prompted by sexual exposure that were prescribed at the Los Angeles LGBT Center between March 2010 and July 2014. Fisher exact tests and logistic regressions were used to determine characteristics that distinguished nPEP seroconverters from non-seroconverters. Results. Of the nPEP courses administered, 1744 had a follow-up visit for HIV testing within 24 weeks of exposure and 17 individuals seroconverted. Seven reported a known re-exposure, 8 self-reported only condom-protected sex subsequent to the initial exposure, and 2 reported abstinence since the exposure. In multivariable analyses, seroconverters were more likely than non-seroconverters to report methamphetamine use, incomplete medication adherence, and nPEP initiation later in the 72-hour window. Conclusions. Nonoccupational postexposure prophylaxis is an important emergency tool for HIV prevention. Our findings corroborate that timing of the initial nPEP dose is an important predictor of seroconversion. Although the current study did not offer the initial nPEP dose at the beginning of the visit, use of this fast-track dosing schedule will ensure that the first dose is taken as early as possible postexposure and may lower the likelihood for seroconversion. Furthermore, we recommend systematic screening for substance use because these individuals may be well suited for pre-exposure prophylaxis given their sustained risk. PMID:28596981

Calibration of Kodak EDR2 film for patient skin dose assessment in cardiac catheterization procedures.

PubMed

Morrell, Rachel E; Rogers, Andy

2004-12-21

Kodak EDR2 film has been calibrated across the range of exposure conditions encountered in our cardiac catheterization laboratory. Its dose-response function has been successfully modelled, up to the saturation point of 1 Gy. The most important factor affecting film sensitivity is the use of beam filtration. Spectral filtration and kVp together account for a variation in dose per optical density of -10% to +25%, at 160 mGy. The use of a dynamic wedge filter may cause doses to be underestimated by up to 6%. The film is relatively insensitive to variations in batch, field size, exposure rate, time to processing and day-to-day fluctuations in processor performance. Overall uncertainty in the calibration is estimated to be -20% to +40%, at 160 mGy. However, the uncertainty increases at higher doses, as the curve saturates. Artefacts were seen on a number of films, due to faults in the light-proofing of the film packets.

Environmental exposure to low-doses of ionizing radiation. Effects on early nephrotoxicity in mice.

PubMed

Bellés, Montserrat; Gonzalo, Sergio; Serra, Noemí; Esplugas, Roser; Arenas, Meritxell; Domingo, José Luis; Linares, Victoria

2017-07-01

Nuclear accidents of tremendous magnitude, such as those of Chernobyl (1986) and Fukushima (2011), mean that individuals living in the contaminated areas are potentially exposed to ionizing radiation (IR). However, the dose-response relationship for effects of low doses of radiation is not still established. The present study was aimed at investigating in mice the early effects of low-dose internal radiation exposure on the kidney. Adult male (C57BL/6J) mice were divided into three groups. Two groups received a single subcutaneous (s.c.) doses of cesium ( 137 Cs) with activities of 4000 and 8000Bq/kg bw. A third group (control group) received a single s.c. injection of 0.9% saline. To evaluate acute and subacute effects, mice (one-half of each group) were euthanized at 72h and 10 days post-exposure to 137 Cs, respectively. Urine samples were collected for biochemical analysis, including the measurement of F2-isoprostane (F2-IsoP) and kidney injury molecule-1 (KIM-1) levels. Moreover, the concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA damage, were measured in renal tissue. Urinary excretion of total protein significantly increased at 72h in mice exposed to Cs4000. Uric acid and lactate dehydrogenase (LDH) decreased significantly at both times post-exposure in animals exposed to Cs8000. After 72h and 10d of exposure to Cs4000, a significant increase in the γ-glutamil transferase (GGT) and N-acetyl-β-D-glucosaminidase (NAG) activities was observed. In turn, F2-IsoP levels increased -mainly in the Cs4000 group- at 72h post-exposure. Following irradiation ( 137 Cs), the highest level of KIM-1 was corresponded to the Cs4000 group at 72h. Likewise, the main DNA damage was detected in mice exposed to Cs4000, mainly at 10d after irradiation. The alterations observed in several biomarkers suggest an immediate renal damage following exposure to low doses of IR (given as 137 Cs). Further investigations are required to clarify the mechanisms involved in the internal IR-induced nephrotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessing Inhalation Exposures Associated with Contamination Events in Water Distribution Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davis, Michael J.; Janke, Robert; Taxon, Thomas N.

When a water distribution system (WDS) is contaminated, short-term inhalation exposures to airborne contaminants could occur as the result of domestic water use. The most important domestic sources of such exposures are likely to be showering and the use of aerosol-producing humidifiers, i.e., ultrasonic and impeller (cool-mist) units. A framework is presented for assessing the potential effects of short-term, system-wide inhalation exposures that could result from such activities during a contamination event. This framework utilizes available statistical models for showering frequency and duration, available exposure models for showering and humidifier use, and experimental results on both aerosol generation and themore » volatilization of chemicals during showering. New models for the times when showering occurs are developed using time-use data for the United States. Given a lack of similar models for how humidifiers are used, or the information needed to develop them, an analysis of the sensitivity of results to assumptions concerning humidifier use is presented. The framework is applied using network models for three actual WDSs. Simple models are developed for estimating upper bounds on the potential effects of system-wide inhalation exposures associated with showering and humidifier use. From a system-wide, population perspective, showering could result in significant inhalation doses of volatile chemical contaminants, and humidifier use could result in significant inhalation doses of microbial contaminants during a contamination event. From a system-wide perspective, showering is unlikely to be associated with significant doses of microbial contaminants. In conclusion, given the potential importance of humidifiers as a source of airborne contaminants during a contamination event, an improved understanding of the nature of humidifier use is warranted.« less

Assessing Inhalation Exposures Associated with Contamination Events in Water Distribution Systems

DOE PAGES

Davis, Michael J.; Janke, Robert; Taxon, Thomas N.

2016-12-08

When a water distribution system (WDS) is contaminated, short-term inhalation exposures to airborne contaminants could occur as the result of domestic water use. The most important domestic sources of such exposures are likely to be showering and the use of aerosol-producing humidifiers, i.e., ultrasonic and impeller (cool-mist) units. A framework is presented for assessing the potential effects of short-term, system-wide inhalation exposures that could result from such activities during a contamination event. This framework utilizes available statistical models for showering frequency and duration, available exposure models for showering and humidifier use, and experimental results on both aerosol generation and themore » volatilization of chemicals during showering. New models for the times when showering occurs are developed using time-use data for the United States. Given a lack of similar models for how humidifiers are used, or the information needed to develop them, an analysis of the sensitivity of results to assumptions concerning humidifier use is presented. The framework is applied using network models for three actual WDSs. Simple models are developed for estimating upper bounds on the potential effects of system-wide inhalation exposures associated with showering and humidifier use. From a system-wide, population perspective, showering could result in significant inhalation doses of volatile chemical contaminants, and humidifier use could result in significant inhalation doses of microbial contaminants during a contamination event. From a system-wide perspective, showering is unlikely to be associated with significant doses of microbial contaminants. In conclusion, given the potential importance of humidifiers as a source of airborne contaminants during a contamination event, an improved understanding of the nature of humidifier use is warranted.« less

Biological exposure indices of pyrrole adducts in serum and urine for hazard assessment of n-hexane exposure.

PubMed

Yin, Hongyin; Zhang, Chunling; Guo, Ying; Shao, Xiaoying; Zeng, Tao; Zhao, Xiulan; Xie, Keqin

2014-01-01

Pyrrole adducts might be used as a biomarker for monitoring occupational exposure to n-hexane, but the Biological Exposure Indices of pyrrole adducts in serum and urine are still unknown. The current study was designed to investigate the biological exposure limit of pyrrole adducts for hazard assessment of n-hexane. Male Wistar rats were given daily dose of 500, 1000, 1500, 2000, 4000 mg/kg bw n-hexane by gavage for 24 weeks. The levels of pyrrole adducts in serum and urine were determined at 8, 24 hours postdose once a week. The Biological Exposure Indices was evaluated by neurological evaluation and the levels of pyrrole adducts. The difference in pyrrole adducts formation between humans and rats were estimated by using in vitro test. Dose-dependent effects were observed between the doses of n-hexane and pyrrole adducts in serum and urine, and the levels of pyrrole adduct in serum and urine approached a plateau at week 4. There was a significantly negative correlation between the time to paralysis and the level of pyrrole adducts in serum and urine, while a positive correlation between gait score and levels of pyrrole adducts in serum and urine was observed. In vitro, pyrrole adducts formed in human serum was about two times more than those in rat serum at the same level of 2,5-HD. It was concluded that the BEIs of pyrrole adducts in humans were 23.1 ± 5.91 nmol/ml in serum 8 h postdose, 11.7 ± 2.64 nmol/ml in serum 24 h postdose, 253.8 ± 36.3 nmol/ml in urine 8 h postdose and 54.6 ± 15.42 nmol/ml in urine 24 h postdose.

Biological Exposure Indices of Pyrrole Adducts in Serum and Urine for Hazard Assessment of n-Hexane Exposure

PubMed Central

Yin, Hongyin; Zhang, Chunling; Guo, Ying; Shao, Xiaoying; Zeng, Tao; Zhao, Xiulan; Xie, Keqin

2014-01-01

Background Pyrrole adducts might be used as a biomarker for monitoring occupational exposure to n-hexane, but the Biological Exposure Indices of pyrrole adducts in serum and urine are still unknown. The current study was designed to investigate the biological exposure limit of pyrrole adducts for hazard assessment of n-hexane. Methods Male Wistar rats were given daily dose of 500, 1000, 1500, 2000, 4000 mg/kg bw n-hexane by gavage for 24 weeks. The levels of pyrrole adducts in serum and urine were determined at 8, 24 hours postdose once a week. The Biological Exposure Indices was evaluated by neurological evaluation and the levels of pyrrole adducts. The difference in pyrrole adducts formation between humans and rats were estimated by using in vitro test. Results Dose-dependent effects were observed between the doses of n-hexane and pyrrole adducts in serum and urine, and the levels of pyrrole adduct in serum and urine approached a plateau at week 4. There was a significantly negative correlation between the time to paralysis and the level of pyrrole adducts in serum and urine, while a positive correlation between gait score and levels of pyrrole adducts in serum and urine was observed. In vitro, pyrrole adducts formed in human serum was about two times more than those in rat serum at the same level of 2,5-HD. Conclusion It was concluded that the BEIs of pyrrole adducts in humans were 23.1±5.91 nmol/ml in serum 8 h postdose, 11.7±2.64 nmol/ml in serum 24 h postdose, 253.8±36.3 nmol/ml in urine 8 h postdose and 54.6±15.42 nmol/ml in urine 24 h postdose. PMID:24465904

Assessing human variability in kinetics for exposures to multiple environmental chemicals: a physiologically based pharmacokinetic modeling case study with dichloromethane, benzene, toluene, ethylbenzene, and m-xylene.

PubMed

Valcke, Mathieu; Haddad, Sami

2015-01-01

The objective of this study was to compare the magnitude of interindividual variability in internal dose for inhalation exposure to single versus multiple chemicals. Physiologically based pharmacokinetic models for adults (AD), neonates (NEO), toddlers (TODD), and pregnant women (PW) were used to simulate inhalation exposure to "low" (RfC-like) or "high" (AEGL-like) air concentrations of benzene (Bz) or dichloromethane (DCM), along with various levels of toluene alone or toluene with ethylbenzene and xylene. Monte Carlo simulations were performed and distributions of relevant internal dose metrics of either Bz or DCM were computed. Area under the blood concentration of parent compound versus time curve (AUC)-based variability in AD, TODD, and PW rose for Bz when concomitant "low" exposure to mixtures of increasing complexities occurred (coefficient of variation (CV) = 16-24%, vs. 12-15% for Bz alone), but remained unchanged considering DCM. Conversely, AUC-based CV in NEO fell (15 to 5% for Bz; 12 to 6% for DCM). Comparable trends were observed considering production of metabolites (AMET), except for NEO's CYP2E1-mediated metabolites of Bz, where an increased CV was observed (20 to 71%). For "high" exposure scenarios, Cmax-based variability of Bz and DCM remained unchanged in AD and PW, but decreased in NEO (CV= 11-16% to 2-6%) and TODD (CV= 12-13% to 7-9%). Conversely, AMET-based variability for both substrates rose in every subpopulation. This study analyzed for the first time the impact of multiple exposures on interindividual variability in toxicokinetics. Evidence indicates that this impact depends upon chemical concentrations and biochemical properties, as well as the subpopulation and internal dose metrics considered.

Assessing Inhalation Exposures Associated with Contamination Events in Water Distribution Systems

PubMed Central

Davis, Michael J.; Janke, Robert; Taxon, Thomas N.

2016-01-01

When a water distribution system (WDS) is contaminated, short-term inhalation exposures to airborne contaminants could occur as the result of domestic water use. The most important domestic sources of such exposures are likely to be showering and the use of aerosol-producing humidifiers, i.e., ultrasonic and impeller (cool-mist) units. A framework is presented for assessing the potential effects of short-term, system-wide inhalation exposures that could result from such activities during a contamination event. This framework utilizes available statistical models for showering frequency and duration, available exposure models for showering and humidifier use, and experimental results on both aerosol generation and the volatilization of chemicals during showering. New models for the times when showering occurs are developed using time-use data for the United States. Given a lack of similar models for how humidifiers are used, or the information needed to develop them, an analysis of the sensitivity of results to assumptions concerning humidifier use is presented. The framework is applied using network models for three actual WDSs. Simple models are developed for estimating upper bounds on the potential effects of system-wide inhalation exposures associated with showering and humidifier use. From a system-wide, population perspective, showering could result in significant inhalation doses of volatile chemical contaminants, and humidifier use could result in significant inhalation doses of microbial contaminants during a contamination event. From a system-wide perspective, showering is unlikely to be associated with significant doses of microbial contaminants. Given the potential importance of humidifiers as a source of airborne contaminants during a contamination event, an improved understanding of the nature of humidifier use is warranted. PMID:27930709

Pulmonary instillation of low doses of titanium dioxide nanoparticles in mice leads to particle retention and gene expression changes in the absence of inflammation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Husain, Mainul, E-mail: mainul.husain@hc-sc.gc.ca; Saber, Anne T., E-mail: ats@nrcwe.dk; Guo, Charles, E-mail: charles.guo@hc-sc.gc.ca

2013-06-15

We investigated gene expression, protein synthesis, and particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO{sub 2}). Female C57BL/6 mice were exposed to rutile nano-TiO{sub 2} via single intratracheal instillations of 18, 54, and 162 μg/mouse. Mice were sampled 1, 3, and 28 days post-exposure. The deposition of nano-TiO{sub 2} in the lungs was assessed using nanoscale hyperspectral microscopy. Biological responses in the pulmonary system were analyzed using DNA microarrays, pathway-specific real-time RT-PCR (qPCR), gene-specific qPCR arrays, and tissue protein ELISA. Hyperspectral mapping showed dose-dependent retention of nano-TiO{sub 2} in the lungs upmore » to 28 days post-instillation. DNA microarray analysis revealed approximately 3000 genes that were altered across all treatment groups (± 1.3 fold; p < 0.1). Several inflammatory mediators changed in a dose- and time-dependent manner at both the mRNA and protein level. Although no influx of neutrophils was detected at the low dose, changes in the expression of several genes and proteins associated with inflammation were observed. Resolving inflammation at the medium dose, and lack of neutrophil influx in the lung fluid at the low dose, were associated with down-regulation of genes involved in ion homeostasis and muscle regulation. Our gene expression results imply that retention of nano-TiO{sub 2} in the absence of inflammation over time may potentially perturb calcium and ion homeostasis, and affect smooth muscle activities. - Highlights: • Pulmonary effects following exposure to low doses of nano-TiO{sub 2} were examined. • Particle retention in lungs was assessed using nanoscale hyperspectral microscopy. • Particles persisted up to 28 days in lungs in all dose groups. • Inflammation was the pathway affected in the high dose group at all time points. • Ion homeostasis and muscle activity pathways were affected in the low dose group.« less

Daily, seasonal, and latitudinal variations in solar ultraviolet A and B radiation in relation to vitamin D production and risk for skin cancer.

PubMed

Grigalavicius, Mantas; Moan, Johan; Dahlback, Arne; Juzeniene, Asta

2016-01-01

Solar ultraviolet (UV) radiation varies with latitude, time of day, and season. Both spectral UV composition and ambient UV dose lead to different health outcomes at different latitudes. Finding the optimal time for sun exposure, whereby the positive effects of UV exposure (vitamin D) are facilitated and the negative effects (skin cancer, photoimmunosuppression) avoided are the most important consideration in modern skin cancer prevention programs. This paper focuses on the latitude dependency of UVB, UVA, vitamin D production, and skin cancer risk in Caucasians. Biologically effective UVB (280-315 nm) and UVA (315-400 nm) doses were calculated using radiative transfer models with appropriate climatologic data for selected locations. Incidences of squamous cell carcinoma (SCC) and cutaneous melanoma (CM) were retrieved from cancer registries and published articles. Annual doses of UVA radiation decrease much less with increasing latitude than annual doses of UVB. Incidences of CM also decrease less steeply with increasing latitude than incidences of SCC. As SCC is caused mainly by UVB, these observations support the assumption that UVA plays an important role in the development of CM. The variations in UVA (relevant to CM) and UVB (relevant to vitamin D production) over 1 day differ: the UVB : UVA ratio is maximal at noon. The best way to obtain a given dose of vitamin D with minimal carcinogenic risk is through a non-burning exposure in the middle of the day, rather than in the afternoon or morning. © 2015 The International Society of Dermatology.

Comparative analysis of the countermeasures taken to mitigate exposure of the public to radioiodine following the Chernobyl and Fukushima accidents: lessons from both accidents.

PubMed

Uyba, Vladimir; Samoylov, Alexander; Shinkarev, Sergey

2018-04-01

In the case of a severe radiation accident at a nuclear power station, the most important radiation hazard for the public is internal exposure of the thyroid to radioiodine. The purposes of this paper were (i) to compare countermeasures conducted (following the Chernobyl and Fukushima accidents) aimed at mitigation of exposure to the thyroid for the public, (ii) to present comparative estimates of doses to the thyroid and (iii) to derive lessons from the two accidents. The scale and time of countermeasures applied in the early phase of the accidents (sheltering, evacuation, and intake of stable iodine to block the thyroid) and at a later time (control of 131I concentration in foodstuffs) have been described. After the Chernobyl accident, the estimation of the thyroid doses for the public was mainly based on direct thyroid measurements of ~400 000 residents carried out within the first 2 months. The highest estimates of thyroid doses to children reached 50 Gy. After the Fukushima accident, the estimation of thyroid doses was based on radioecological models due to a lack of direct thyroid measurements (only slightly more than 1000 residents were measured). The highest estimates of thyroid doses to children were a few hundred mGy. Following the Chernobyl accident, ingestion of 131I through cows' milk was the dominant pathway. Following the Fukushima accident, it appears that inhalation of contaminated air was the dominant pathway. Some lessons learned following the Chernobyl and Fukushima accidents have been presented in this paper.

Comparative analysis of the countermeasures taken to mitigate exposure of the public to radioiodine following the Chernobyl and Fukushima accidents: lessons from both accidents

PubMed Central

Uyba, Vladimir; Samoylov, Alexander; Shinkarev, Sergey

2018-01-01

Abstract In the case of a severe radiation accident at a nuclear power station, the most important radiation hazard for the public is internal exposure of the thyroid to radioiodine. The purposes of this paper were (i) to compare countermeasures conducted (following the Chernobyl and Fukushima accidents) aimed at mitigation of exposure to the thyroid for the public, (ii) to present comparative estimates of doses to the thyroid and (iii) to derive lessons from the two accidents. The scale and time of countermeasures applied in the early phase of the accidents (sheltering, evacuation, and intake of stable iodine to block the thyroid) and at a later time (control of 131I concentration in foodstuffs) have been described. After the Chernobyl accident, the estimation of the thyroid doses for the public was mainly based on direct thyroid measurements of ~400 000 residents carried out within the first 2 months. The highest estimates of thyroid doses to children reached 50 Gy. After the Fukushima accident, the estimation of thyroid doses was based on radioecological models due to a lack of direct thyroid measurements (only slightly more than 1000 residents were measured). The highest estimates of thyroid doses to children were a few hundred mGy. Following the Chernobyl accident, ingestion of 131I through cows’ milk was the dominant pathway. Following the Fukushima accident, it appears that inhalation of contaminated air was the dominant pathway. Some lessons learned following the Chernobyl and Fukushima accidents have been presented in this paper. PMID:29415268

Capstone Depleted Uranium Aerosol Biokinetics, Concentrations, and Doses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guilmette, Raymond A.; Miller, Guthrie; Parkhurst, MaryAnn

2009-02-26

One of the principal goals of the Capstone Depleted Uranium (DU) Aerosol Study was to quantify and characterize DU aerosols generated inside armored vehicles by perforation with a DU penetrator. This study consequently produced a database in which the DU aerosol source terms were specified both physically and chemically for a variety of penetrator-impact geometries and conditions. These source terms were used to calculate radiation doses and uranium concentrations for various scenarios as part of the Capstone DU Human Health Risk Assessment (HHRA). This paper describes the scenario-related biokinetics of uranium, and summarizes intakes, chemical concentrations to the organs, andmore » E(50) and HT(50) for organs and tissues based on exposure scenarios for personnel in vehicles at the time of perforation as well as for first responders. For a given exposure scenario (duration time and breathing rates), the range of DU intakes among the target vehicles and shots was not large, about a factor of 10, with the lowest being from a ventilated operational Abrams tank and the highest being for an unventilated Abrams with DU penetrator perforating DU armor. The ranges of committed effective doses were more scenario-dependent than were intakes. For example, the largest range, a factor of 20, was shown for scenario A, a 1-min exposure, whereas, the range was only a factor of two for the first-responder scenario (E). In general, the committed effective doses were found to be in the tens of mSv. The risks ascribed to these doses are discussed separately.« less

A PROBABILISTIC EXPOSURE ASSESSMENT FOR CHILDREN WHO CONTACT CCA-TREATED PLAYSETS AND DECKS USING THE STOCHASTIC HUMAN EXPOSURE AND DOSE SIMULATION (SHEDS) MODEL FOR THE WOOD PRESERVATIVE EXPOSURE SCENARIO

EPA Science Inventory

The U.S. Environmental Protection Agency has conducted a probabilistic exposure and dose assessment on the arsenic (As) and chromium (Cr) components of Chromated Copper Arsenate (CCA) using the Stochastic Human Exposure and Dose Simulation model for wood preservatives (SHEDS-Wood...

Improving photoprotection attitudes in the tropics: sunburn vs vitamin D.

PubMed

Silva, Abel A

2014-01-01

The ultraviolet radiation of type B (the UVB) stimulates both the production of vitamin D (VD) and the incorporation of erythema dose (ED). The UVA also contributes to ED. The turning point between the benefit of producing VD and the harm of incorporating ED cannot be determined easily. However, the casual behavior regarding the exposure to the Sun can be changed in order to improve the protoprotection attitudes and create a trend towards benefit. In the case, people living in the low latitudes should exposure themselves to the Sun for a determined time interval within the noon time and avoid the Sun in other periods. This would produce an adequate amount of VD through the VD dose (207-214 J m(-2)) against minimum ED (≈105 J m(-2)) for skin type II. For it, unprotected forearms and hands must be exposed to the noon Sun (cloudless) for 11 min (winter) and 5 min (summer). The exposure at other times different from noon can represent increases of up to 24% in ED and up to 12 times in the time interval to be in the Sun in relation to the minimum amounts of both ED and time interval at noon. © 2014 The American Society of Photobiology.

Analysis of Patients' X-ray Exposure in 146 Percutaneous Radiologic Gastrostomies.

PubMed

Petersen, Tim-Ole; Reinhardt, Martin; Fuchs, Jochen; Gosch, Dieter; Surov, Alexey; Stumpp, Patrick; Kahn, Thomas; Moche, Michael

2017-09-01

Purpose  Analysis of patient´s X-ray exposure during percutaneous radiologic gastrostomies (PRG) in a larger population. Materials and Methods  Data of primary successful PRG-procedures, performed between 2004 and 2015 in 146 patients, were analyzed regarding the exposition to X-ray. Dose-area-product (DAP), dose-length-product (DLP) respectively, and fluoroscopy time (FT) were correlated with the used x-ray systems (Flatpanel Detector (FD) vs. Image Itensifier (BV)) and the necessity for periprocedural placement of a nasogastric tube. Additionally, the effective X-ray dose for PRG placement using fluoroscopy (DL), computed tomography (CT), and cone beam CT (CBCT) was estimated using a conversion factor. Results  The median DFP of PRG-placements under fluoroscopy was 163 cGy*cm 2 (flat panel detector systems: 155 cGy*cm 2 ; X-ray image intensifier: 175 cGy*cm 2 ). The median DLZ was 2.2 min. Intraprocedural placement of a naso- or orogastric probe (n = 68) resulted in a significant prolongation of the median DLZ to 2.5 min versus 2 min in patients with an already existing probe. In addition, dose values were analyzed in smaller samples of patients in which the PRG was placed under CBCT (n = 7, median DFP = 2635 cGy*cm 2 ), or using CT (n = 4, median DLP = 657 mGy*cm). Estimates of the median DFP and DLP showed effective doses of 0.3 mSv for DL-assisted placements (flat panel detector 0.3 mSv, X-ray image converter 0.4 mSv), 7.9 mSv using a CBCT - flat detector, and 9.9 mSv using CT. This corresponds to a factor 26 of DL versus CBCT, or a factor 33 of DL versus CT. Conclusion  In order to minimize X-ray exposure during PRG-procedures for patients and staff, fluoroscopically-guided interventions should employ flat detector systems with short transmittance sequences in low dose mode and with slow image frequency. Series recordings can be dispensed with. The intraprocedural placement of a naso- or orogastric probe significantly extends FT, but has little effect on the overall dose of the intervention. Due to the significantly higher X-ray exposure, the use of a CBCT as well as PRG-placements using CT should be limited to clinically absolutely necessary exceptions with strict indication. Key Points   · Fluoroscopically-guided PRG placements are interventions with low X-ray exposure.. · X-ray exposure from fluoroscopy is lower using flat panel detector systems as compared to image intensifier systems.. · The concomitant placement of an oro- or nasogastric probe extends the fluoroscopy time.. · Gastric probe placement is worthwhile to prevent the premature use of the significantly radiation-intensive CT.. · The use of the C-arm CT or the CT increases the beam exposure by 26 or 33 times, respectively.. · The PRG placement using C-arm CT and CT should only be performed in exceptional cases.. Citation Format · Petersen TO, Reinhardt M, Fuchs J et al. Analysis of Patients' X-ray Exposure in 146 Percutaneous Radiologic Gastrostomies. Fortschr Röntgenstr 2017; 189: 820 - 827. © Georg Thieme Verlag KG Stuttgart · New York.

Defining the optimal dose of rifapentine for pulmonary tuberculosis: Exposure–response relations from two phase II clinical trials

PubMed Central

Savic, RM; MacKenzie, WR; Engle, M; Whitworth, WC; Johnson, JL; Nsubuga, P; Nahid, P; Nguyen, NV; Peloquin, CA; Dooley, KE; Dorman, SE

2017-01-01

Rifapentine is a highly active antituberculosis antibiotic with treatment‐shortening potential; however, exposure–response relations and the dose needed for maximal bactericidal activity have not been established. We used pharmacokinetic/pharmacodynamic data from 657 adults with pulmonary tuberculosis participating in treatment trials to compare rifapentine (n = 405) with rifampin (n = 252) as part of intensive‐phase therapy. Population pharmacokinetic/pharmacodynamic analyses were performed with nonlinear mixed‐effects modeling. Time to stable culture conversion of sputum to negative was determined in cultures obtained over 4 months of therapy. Rifapentine exposures were lower in participants who were coinfected with human immunodeficiency virus, black, male, or fasting when taking drug. Rifapentine exposure, large lung cavity size, and geographic region were independently associated with time to culture conversion in liquid media. Maximal treatment efficacy is likely achieved with rifapentine at 1,200 mg daily. Patients with large lung cavities appear less responsive to treatment, even at high rifapentine doses. PMID:28124478

Considerations for the design and technical setup of a human whole-body exposure chamber.

PubMed

Monsé, Christian; Sucker, Kirsten; van Thriel, Christoph; Broding, Horst Christoph; Jettkant, Birger; Berresheim, Hans; Wiethege, Thorsten; Käfferlein, Heiko; Merget, Rolf; Bünger, Jürgen; Brüning, Thomas

2012-01-01

Exposures to air contaminants, such as chemical vapors and particulate matter, pose important health hazards at workplaces. Short-term experimental exposures to chemical vapors and particles in humans are a promising attempt to investigate acute effects of such hazards. However, a significant challenge in this field is the determination of effects of co-exposures to more than one chemical or mixtures of chemical vapors and/or particles. To overcome such a challenge, studies have to be conducted under standardized exposure characterization and real time measurements, if possible. A new exposure laboratory (ExpoLab) was installed at IPA, combining sophisticated engineering designs with new analytical techniques, to fulfill these requirements. Low-dose as well as high-dose exposure scenarios are achieved by means of a calibration-gas-generator. Exposure monitoring can be carried out with a high performance real time mass spectrometer and other suitable analyzers (e.g. gas chromatograph). Numerous automated security facilities guarantee the physical integrity of the volunteers, and the waste atmosphere is removed using either charcoal filtration or catalytic post-combustion. Measurements of sulfur hexafluoride, carbon dioxide, aniline and carbon black are presented to demonstrate the performance of the exposure unit with respect to the temporal and spatial stability of generated atmospheres. The variations of generated contents in the atmospheres at steady state are slightly higher than the measurement precision of the analyzers (the typical standard deviation of generated atmospheres is < 2%). The technical components of ExpoLab and its monitoring systems ensure high quality standards in validity and reliability of generating and measuring exposure atmospheres.

Radiation Exposure and Vascular Access in Acute Coronary Syndromes: The RAD-Matrix Trial.

PubMed

Sciahbasi, Alessandro; Frigoli, Enrico; Sarandrea, Alessandro; Rothenbühler, Martina; Calabrò, Paolo; Lupi, Alessandro; Tomassini, Francesco; Cortese, Bernardo; Rigattieri, Stefano; Cerrato, Enrico; Zavalloni, Dennis; Zingarelli, Antonio; Calabria, Paolo; Rubartelli, Paolo; Sardella, Gennaro; Tebaldi, Matteo; Windecker, Stephan; Jüni, Peter; Heg, Dik; Valgimigli, Marco

2017-05-23

It remains unclear whether radial access increases the risk of operator or patient radiation exposure compared to transfemoral access when performed by expert operators. This study sought to determine whether radial access increases radiation exposure. A total of 8,404 patients, with or without ST-segment elevation acute coronary syndrome, were randomly assigned to radial or femoral access for coronary angiography and percutaneous intervention, and collected fluoroscopy time and dose-area product (DAP). RAD-MATRIX is a radiation sub-study of the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) trial. We anticipated that 13 or more operators, each wearing a thorax (primary endpoint), wrist, and head (secondary endpoints) lithium fluoride thermoluminescent dosimeter, and randomizing at least 13 patients per access site, were needed to establish noninferiority of radial versus femoral access. Among 18 operators, performing 777 procedures in 767 patients, the noninferiority primary endpoint was not achieved (p value for noninferiority = 0.843). Operator equivalent dose at the thorax (77 μSv) was significantly higher with radial than femoral access (41 μSv; p = 0.02). After normalization of operator radiation dose by fluoroscopy time or DAP, the difference remained significant. Radiation dose at wrist or head did not differ between radial and femoral access. Thorax operator dose did not differ for right radial (84 μSv) compared to left radial access (52 μSv; p = 0.15). In the overall MATRIX population, fluoroscopy time and DAP were higher with radial compared to femoral access: 10 min versus 9 min (p < 0.0001) and 65 Gy·cm 2 versus 59 Gy·cm 2 (p = 0.0001), respectively. Compared to femoral access, radial access is associated with greater operator and patient radiation exposure when performed by expert operators in current practice. Radial operators and institutions should be sensitized towards radiation risks and adopt adjunctive radioprotective measures. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX; NCT101433627). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Six months exposure to a real life mixture of 13 chemicals' below individual NOAELs induced non monotonic sex-dependent biochemical and redox status changes in rats.

PubMed

Docea, Anca Oana; Gofita, Eliza; Goumenou, Marina; Calina, Daniela; Rogoveanu, Otilia; Varut, Marius; Olaru, Cristian; Kerasioti, Efthalia; Fountoucidou, Polyxeni; Taitzoglou, Ioannis; Zlatian, Ovidiu; Rakitskii, Valerii N; Hernandez, Antonio F; Kouretas, Dimitrios; Tsatsakis, Aristidis

2018-05-01

This study assessed the potential adverse health effects of long-term low-dose exposure to chemical mixtures simulating complex real-life human exposures. Four groups of Sprague Dawley rats were administered mixtures containing carbaryl, dimethoate, glyphosate, methomyl, methyl parathion, triadimefon, aspartame, sodium benzoate, calcium disodium ethylene diamine tetra-acetate, ethylparaben, butylparaben, bisphenol A, and acacia gum at doses of 0, 0.25, 1 or 5 times the respective Toxicological Reference Values (TRV): acceptable daily intake (ADI) or tolerable daily intake (TDI) in a 24 weeks toxicity study. Body weight gain, feed and water consumption were evaluated weekly. At 24 weeks blood was collected and biochemistry parameters and redox status markers were assessed. Adverse effects were observed on body weight gain and in hepatotoxic parameters such as the total bilirubin, alanine aminotransferase (ALT) and alkaline phosphatase (ALP), especially in low dose and affecting mainly male rats. The low dose group showed increased catalase activity both in females and males, whereas the high dose group exhibited decreased protein carbonyl and total antioxidant capacity (TAC) levels in both sex groups. Non-monotonic effects and adaptive responses on liver function tests and redox status, leading to non-linear dose-responses curves, are probably produced by modulation of different mechanisms. Copyright © 2018. Published by Elsevier Ltd.

Real Time Radiation Exposure And Health Risks

NASA Technical Reports Server (NTRS)

Hu, Shaowen; Barzilla, Janet E.; Semones, Edward J.

2015-01-01

Radiation from solar particle events (SPEs) poses a serious threat to future manned missions outside of low Earth orbit (LEO). Accurate characterization of the radiation environment in the inner heliosphere and timely monitoring the health risks to crew are essential steps to ensure the safety of future Mars missions. In this project we plan to develop an approach that can use the particle data from multiple satellites and perform near real-time simulations of radiation exposure and health risks for various exposure scenarios. Time-course profiles of dose rates will be calculated with HZETRN and PDOSE from the energy spectrum and compositions of the particles archived from satellites, and will be validated from recent radiation exposure measurements in space. Real-time estimation of radiation risks will be investigated using ARRBOD. This cross discipline integrated approach can improve risk mitigation by providing critical information for risk assessment and medical guidance to crew during SPEs.

Public exposure due to external gamma background radiation in boundary areas of Iran.

PubMed

Pooya, S M Hosseini; Dashtipour, M R; Enferadi, A; Orouji, T

2015-09-01

A monitoring program in boundary areas of a country is an appropriate way to indicate the level of public exposure. In this research, gamma background radiation was measured using TL dosimeters at 12 boundary areas as well as in the capital city of Iran during the period 2010 to 2011. The measurements were carried out in semi-annual time intervals from January to June and July to December in each year. The maximum average dose equivalent value measured was approximately 70 μSv/month for Tehran city. Also, the average dose values obtained were less than 40 μSv/month for all the cities located at the sea level except that of high level natural radiation area of Ramsar, and more than 55 μSv/month for the higher elevation cities. The public exposure due to ambient gamma dose equivalent in Iran is within the levels reported by UNSCEAR. Copyright © 2015 Elsevier Ltd. All rights reserved.

DOSE ASSESSMENTS FROM THE DISPOSAL OF LOW ...

EPA Pesticide Factsheets

Modeling the long-term performance of the RCRA-C disposal cell and potential doses to off-site receptors is used to derive maximum radionuclide specific concentrations in the wastes that would enable these wastes to be disposed of safely using the RCRA-C disposal cell technology. Modeling potential exposures to derive these waste acceptance concentrations involves modeling exposures to workers during storage, treatment and disposal of the wastes, as well as exposures to individuals after disposal operations have ceased. Post facility closure exposures can result from the slow expected degradation of the disposal cell over long time periods (one thousand years after disposal) and in advertent human intrusion. Provide a means of determining waste acceptance radionuclide concentrations for disposal of debris from radiological dispersal device incidents as well as low-activity wastes generated in commercial, medical and research activities, potentially serve as the technical basis for guidance on disposal of these materials.

Concerted application of LC-MS and ligand binding assays to better understand exposure of a large molecule drug.

PubMed

Xu, Weifeng; Jiang, Hao; Titsch, Craig; Gadkari, Snaehal; Batog, Alicja; Wang, Bonnie; Hippeli, Lauren; Yamamoto, Brent; Chadwick, Kristina; Wheeler, Jennifer; Thompson, Chris; Stahl, James; Willett, Scott; DeSilva, Binodh S; Myler, Heather; Dodge, Robert W; Pillutla, Renuka C

2018-06-20

A ligand-binding assay (LBA) was used to measure exposure of PRM-151, the recombinant form of human pentraxin-2 (PTX-2), a complex pentamer with multiple binding partners. However, the assay showed a lack of dose-dependent exposure in select preclinical species and it could not differentiate the infused PRM-151 from the endogenous PTX-2 in nonhuman primates. Instead of assessing interference from its multiple binding partners, which could be time consuming and laborious, a LC-MS assay avoid of these interference was implemented to measure 'total' drug without the use of immunoaffinity capture reagents. The resultant LC-MS data confirmed the original data and the lack of dose-dependent exposure is now understood to be due to the multiple and diverse targets and functions and resultant complex biodistribution rather than an assay artifact.

[Efficacy evaluation of acupoints massage on asthenopia of video display terminal under different exposure dose].

PubMed

Xu, Yan; Gu, Guang-Xia; Yang, Xiao-Sheng; Pan, Chun-Ying; Hou, Wen-Li; Zhao, Wei; Xing, Qin

2012-04-01

To observe the efficacy differences of acupoints massage for asthenopia of video display terminal (VDT) under different exposure dose. One hundred and two cases (204 eyes) were divided into a low exposure group and a high exposure group, fifty-one cases in each group. The same intervention of acupoints massage on Cuanzhu (BL 2), Jingming (BL 1), Sizhukong (TE 23), Sibai (ST 2) and Taiyang(EX-HN 5) were given to the two groups, one acupoint for 5 min and once everyday, one month of which made a course. The symptom score, tear film break-up time (BUT) and Schirmer I test(SIT) were observed before and after treatment. (1) The correlation coefficient of cubic curve model of the exposure dose was the biggest with symptom improvement index (P = 0.000), which indicated that the lower VDT exposure index was, the more obvious the symptom improved. The symptom improvement indices of low exposure group and high exposure group, which were (52.31 +/- 16.65)% and (28.93 +/- 13.35)% respectively, were statistical significant difference (P = 0.000). (2) Compared to before treatment, the levels of BUT and SIT in the two groups were both significantly higher (P < 0.05). Compared with the high exposure group, the levels of BUT and SIT in the low exposure group were increased by 0.826 s (P = 0.022) and 1.029 mm (P = 0.033), respectively, after the impact of BUT and SIT was corrected before the research. The acupoints massage can improve the symptoms and ocular physiology for patients with VDT asthenpia, and it is more effective for the low exposure cases.

Changes in Mipomersen Dosing Regimen Provide Similar Exposure With Improved Tolerability in Randomized Placebo‐Controlled Study of Healthy Volunteers

PubMed Central

Flaim, JoAnn D.; Grundy, John S.; Baker, Brenda F.; McGowan, Mary P.; Kastelein, John J. P.

2014-01-01

Background Mipomersen, an apolipoprotein B synthesis inhibitor, demonstrated significant reductions in low‐density lipoprotein (LDL) cholesterol, non‐high density lipoprotein cholesterol, and apolipoprotein B in 4 phase 3 studies at the FDA‐approved subcutaneous dose of 200 mg once weekly. Methods and Results A short‐term phase 1 study in healthy volunteers was conducted to evaluate the relative bioavailability, safety, and tolerability of mipomersen in 2 test dose regimens in reference to the 200 mg weekly dose regimen. Eighty‐four adults were randomized to 1 of 3 cohorts (30 mg once daily, 70 mg 3 times weekly, or 200 mg once weekly) and then mipomersen or placebo (3:1 ratio) for 3 weeks of treatment. Comparable mipomersen post‐distribution phase plasma concentrations were observed across the 3 dose regimens suggesting similar tissue exposure. Injection site reactions were reported, but did not lead to treatment discontinuation. The median incidence of these responses per injection was decreased by lowering the dose. Signals from a diverse panel of systemic inflammation markers were essentially indistinguishable between dose regimens and placebo treatment. The one exception was a modest transient post‐dose elevation of C‐reactive protein (CRP) in the mipomersen 200 mg weekly group. This elevation was not associated with an increase in other proinflammatory markers. Conclusions This study demonstrated a similar drug exposure and overall safety profile between the 3 dosing regimens. Exploratory assessment of a diverse panel of biomarkers found no indication of a systemic inflammatory response to mipomersen treatment. These results support assessment of alternative dose regimens in longer‐term studies. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01061814. PMID:24627419

Changes in mipomersen dosing regimen provide similar exposure with improved tolerability in randomized placebo-controlled study of healthy volunteers.

PubMed

Flaim, Joann D; Grundy, John S; Baker, Brenda F; McGowan, Mary P; Kastelein, John J P

2014-03-13

Mipomersen, an apolipoprotein B synthesis inhibitor, demonstrated significant reductions in low-density lipoprotein (LDL) cholesterol, non-high density lipoprotein cholesterol, and apolipoprotein B in 4 phase 3 studies at the FDA-approved subcutaneous dose of 200 mg once weekly. A short-term phase 1 study in healthy volunteers was conducted to evaluate the relative bioavailability, safety, and tolerability of mipomersen in 2 test dose regimens in reference to the 200 mg weekly dose regimen. Eighty-four adults were randomized to 1 of 3 cohorts (30 mg once daily, 70 mg 3 times weekly, or 200 mg once weekly) and then mipomersen or placebo (3:1 ratio) for 3 weeks of treatment. Comparable mipomersen post-distribution phase plasma concentrations were observed across the 3 dose regimens suggesting similar tissue exposure. Injection site reactions were reported, but did not lead to treatment discontinuation. The median incidence of these responses per injection was decreased by lowering the dose. Signals from a diverse panel of systemic inflammation markers were essentially indistinguishable between dose regimens and placebo treatment. The one exception was a modest transient post-dose elevation of C-reactive protein (CRP) in the mipomersen 200 mg weekly group. This elevation was not associated with an increase in other proinflammatory markers. This study demonstrated a similar drug exposure and overall safety profile between the 3 dosing regimens. Exploratory assessment of a diverse panel of biomarkers found no indication of a systemic inflammatory response to mipomersen treatment. These results support assessment of alternative dose regimens in longer-term studies. http://www.clinicaltrials.gov. Unique identifier: NCT01061814.

Evolution of TUNEL-labeling in the rat lens after in vivo exposure to just above threshold dose UVB.

PubMed

Kronschläger, Martin; Yu, Zhaohua; Talebizadeh, Nooshin; Meyer, Linda M; Hallböök, Finn; Söderberg, Per G

2013-08-01

To quantitatively analyse the evolution of TUNEL-labeling, after in vivo exposure to UVB. Altogether, 16 Sprague Dawley rats were unilaterally exposed in vivo for 15 min to close to threshold dose, 5 kJ/m(2), of ultraviolet radiation in the 300 nm wavelength region. Animals were sacrificed in groups of 4 at 1, 5, 24 and 120 h after exposure. For each animal, both eye globes were removed and frozen. The frozen eye was cryo-sectioned in 10 µm thick midsagittal sections. From each globe, three midsagittal sections with at least five sections interval in between were mounted on a microscope slide. Sections were TUNEL-labeled and counter stained with DAPI. For quantification of apoptosis, a fluorescence microscope was used. In sections with a continuous epithelial cell surface, the number of lens epithelial cell nuclei and the number of TUNEL-positive epithelial cell nuclei was counted. The total number of TUNEL-positive epithelial cell nuclei for all three sections of one lens in relation to the total number of epithelial cell nuclei for all three sections of the same lens was compared between exposed and contralateral not exposed lens for each animal. The relative difference of the fraction of TUNEL-positive nuclei between exposed and contralateral not exposed lens increased gradually, peaked in the time interval 5-120 h after exposure, and then declined. Close to threshold dose of UVB induces TUNEL-labeling that peaks in the time window 5-120 h after exposure to UVB.

Repeated exposures to chlorpyrifos lead to spatial memory retrieval impairment and motor activity alteration.

PubMed

Yan, Changhui; Jiao, Lifei; Zhao, Jun; Yang, Haiying; Peng, Shuangqing

2012-07-01

Chlorpyrifos (CPF) is one of the most commonly used insecticides throughout the world and has become one of the major pesticides detected in farm products. Chronic exposures to CPF, especially at the dosages without eliciting any systemic toxicity, require greater attention. The purpose of this study was, therefore, to evaluate the behavioral effects of repeated low doses (doses that do not produce overt signs of cholinergic toxicity) of CPF in adult rats. Male rats were given 0, 1.0, 5.0 or 10.0mg/kg of CPF through intragastric administration daily for 4 consecutive weeks. The behavioral functions were assessed in a series of behavioral tests, including water maze task, open-field test, grip strength and rotarod test. Furthermore, the present study was designed to evaluate the effects of repeated exposures to CPF on water maze recall and not acquisition. The results showed that the selected doses only had mild inhibition effects on cholinesterase activity, and have no effects on weight gain and daily food consumption. Performances in the spatial retention task (Morris water maze) were impaired after the 4-week exposure to CPF, but the performances of grip strength and rotarod test were not affected. Motor activities in the open field were changed, especially the time spent in the central zone increased. The results indicated that repeated exposures to low doses of CPF may lead to spatial recall impairments, behavioral abnormalities. However, the underlying mechanism needs further investigations. Copyright © 2012 Elsevier Inc. All rights reserved.

Sol-gel derived copper-doped silica glass as a sensitive material for X-ray beam dosimetry

NASA Astrophysics Data System (ADS)

Capoen, Bruno; Hamzaoui, Hicham El; Bouazaoui, Mohamed; Ouerdane, Youcef; Boukenter, Aziz; Girard, Sylvain; Marcandella, Claude; Duhamel, Olivier

2016-01-01

The light emission from a sol-gel-derived Cu-doped silica glass was studied under 10 keV X-ray irradiation using a fibered setup. Both radioluminescence (RL) and optically stimulated luminescence (OSL) were analyzed at different high dose rates up to 50 Gy/s and for different exposure times, yielding accumulated doses up to 50 kGy (in SiO2). Even if a darkening effect appears at this dose level, the material remains X-sensitive after exposure to several kGy. At low dose rate, the scintillation mechanisms are similar to photoluminescence, involving the Cu+ ions electronic levels, contrary to the nonlinear domain (for dose rates higher than 30 Gy/s). This RL, as well as the OSL, could be exploited in their linear domain to measure doses as high as 3 kGy. A thorough study of the OSL signal has shown that it must be employed with caution in order to take the fading phenomenon and the response dependency on stimulation source intensity into consideration.

Elucidating rifampin's inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers: unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its primary metabolite.

PubMed

Zheng, H X; Huang, Y; Frassetto, L A; Benet, L Z

2009-01-01

The effects of single doses of intravenous (IV) ciprofloxacin and rifampin and of multiple doses of rifampin on glyburide exposure and blood glucose levels were investigated in nine healthy volunteers. A single IV dose of rifampin significantly increased the area under the concentration-time curve (AUC) of glyburide and its metabolite. Blood glucose levels were significantly lower than those observed after dosing with glyburide alone. Multiple doses of rifampin induced an increase in liver enzyme levels, leading to a marked decrease in glyburide exposure and blood glucose levels. When IV rifampin was administered after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect; however, the relative changes in AUC for glyburide and its hydroxyl metabolite were similar to those seen under noninduced conditions. The studies reported here demonstrate how measurements of the levels of both the parent drug and its primary metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and in characterizing enzymatic vs. transporter mechanisms.

A study on the dependence of exposure dose reduction and image evaluation on the distance from the dental periapical X-ray machine

NASA Astrophysics Data System (ADS)

Joo, Kyu-Ji; Shin, Jae-Woo; Dong, Kyung-Rae; Lim, Chang-Seon; Chung, Woon-Kwan; Kim, Young-Jae

2013-11-01

Reducing the exposure dose from a periapical X-ray machine is an important aim in dental radiography. Although the radiation exposure dose is generally low, any radiation exposure is harmful to the human body. Therefore, this study developed a method that reduces the exposure dose significantly compared to that encountered in a normal procedure, but still produces an image with a similar resolution. The correlation between the image resolution and the exposure dose of the proposed method was examined with increasing distance between the dosimeter and the X-ray tube. The results were compared with those obtained from the existing radiography method. When periapical radiography was performed once according to the recommendations of the International Commission on Radiological Protection (ICRP), the measured skin surface dose was low at 7 mGy or below. In contrast, the skin surface dose measured using the proposed method was only 1.57 mGy, showing a five-fold reduction. These results suggest that further decreases in dose might be achieved using the proposed method.

Pharmacokinetics, tissue distribution and metabolism of acriflavine and proflavine in the channel catfish (Ictalurus punctatus).

PubMed

Plakas, S M; el Said, K R; Bencsath, F A; Musser, S M; Hayton, W L

1998-06-01

1. The disposition of proflavine (PRO) and acriflavine (ACR) were examined in channel catfish after intravascular (i.v.) dosing (1 mg/kg) or waterborne exposure (10 mg/l for 4 h). 2. After i.v. dosing, plasma concentration-time profiles of parent PRO and ACR were best described by two- and three-compartment pharmacokinetic models respectively. Terminal elimination half-lives of PRO and ACR in plasma were 8.7 and 11.4 h respectively. 3. In animals dosed with 14C-PRO or 14C-ACR, total drug equivalent concentrations were highest in the excretory organs and lowest in muscle, fat and plasma. In PRO-dosed animals, residues in the liver and trunk kidney were composed primarily of glucuronosyl and acetyl conjugates of PRO; residues in muscle were composed mostly (> 95%) of the parent drug. In ACR-dosed animals, the parent compound comprised > 90% of the total residues in all tissues examined. 4. PRO and ACR were poorly absorbed in catfish during waterborne exposure. At the end of a 4-h exposure, parent PRO and ACR concentrations in muscle were 0.064 and 0.020 microgram/g respectively. Levels in muscle declined below the limit of determination (0.005 microgram/g) within 1-2 weeks.

In Vivo Human Time-Exposure Study of Orally Dosed Commercial Silver Nanoparticles

PubMed Central

Munger, Mark A.; Radwanski, Przemyslaw; Hadlock, Greg C.; Stoddard, Greg; Shaaban, Akram; Falconer, Jonathan; Grainger, David W.; Deering-Rice, Cassandra E.

2013-01-01

Background Human biodistribution, bioprocessing and possible toxicity of nanoscale silver receives increasing health assessment. Methods We prospectively studied commercial 10- and 32-ppm nanoscale silver particle solutions in a single-blind, controlled, cross-over, intent-to-treat, design. Healthy subjects (n=60) underwent metabolic, blood counts, urinalysis, sputum induction, and chest and abdomen magnetic resonance imaging. Silver serum and urine content was determined. Results No clinically important changes in metabolic, hematologic, or urinalysis measures were identified. No morphological changes were detected in the lungs, heart or abdominal organs. No significant changes were noted in pulmonary reactive oxygen species or pro-inflammatory cytokine generation. Conclusion In vivo oral exposure to these commercial nanoscale silver particle solutions does not prompt clinically important changes in human metabolic, hematologic, urine, physical findings or imaging morphology. Further study of increasing time exposure and dosing of silver nanoparticulate silver, and observation of additional organ systems is warranted to assert human toxicity thresholds. PMID:23811290

Terbinafine in combination with other antifungal agents for treatment of resistant or refractory mycoses: investigating optimal dosing regimens using a physiologically based pharmacokinetic model.

PubMed

Dolton, Michael J; Perera, Vidya; Pont, Lisa G; McLachlan, Andrew J

2014-01-01

Terbinafine is increasingly used in combination with other antifungal agents to treat resistant or refractory mycoses due to synergistic in vitro antifungal activity; high doses are commonly used, but limited data are available on systemic exposure, and no assessment of pharmacodynamic target attainment has been made. Using a physiologically based pharmacokinetic (PBPK) model for terbinafine, this study aimed to predict total and unbound terbinafine concentrations in plasma with a range of high-dose regimens and also calculate predicted pharmacodynamic parameters for terbinafine. Predicted terbinafine concentrations accumulated significantly during the first 28 days of treatment; the area under the concentration-time curve (AUC)/MIC ratios and AUC for the free, unbound fraction (fAUC)/MIC ratios increased by 54 to 62% on day 7 of treatment and by 80 to 92% on day 28 compared to day 1, depending on the dose regimen. Of the high-dose regimens investigated, 500 mg of terbinafine taken every 12 h provided the highest systemic exposure; on day 7 of treatment, the predicted AUC, maximum concentration (Cmax), and minimum concentration (Cmin) were approximately 4-fold, 1.9-fold, and 4.4-fold higher than with a standard-dose regimen of 250 mg once daily. Close agreement was seen between the concentrations predicted by the PBPK model and the observed concentrations, indicating good predictive performance. This study provides the first report of predicted terbinafine exposure in plasma with a range of high-dose regimens.

Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart.

PubMed

Seawright, John W; Samman, Yusra; Sridharan, Vijayalakshmi; Mao, Xiao Wen; Cao, Maohua; Singh, Preeti; Melnyk, Stepan; Koturbash, Igor; Nelson, Gregory A; Hauer-Jensen, Martin; Boerma, Marjan

2017-01-01

Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation. Cardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy), or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group. The combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen. This study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T-lymphocyte infiltration, and cardiac remodeling in response to HU with simultaneous exposure to low-dose rate γ-radiation. Results from the late observation time points suggest that the hearts had mostly recovered from these two experimental conditions. However, further research is needed with larger numbers of animals for a more robust statistical power to fully characterize the early and late effects of simulated microgravity combined with exposure to low-dose rate ionizing radiation on the heart.

Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart

PubMed Central

Samman, Yusra; Sridharan, Vijayalakshmi; Mao, Xiao Wen; Cao, Maohua; Singh, Preeti; Melnyk, Stepan; Koturbash, Igor; Nelson, Gregory A.; Hauer-Jensen, Martin; Boerma, Marjan

2017-01-01

Purpose Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation. Methods Cardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy), or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group. Results The combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen. Conclusions This study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T-lymphocyte infiltration, and cardiac remodeling in response to HU with simultaneous exposure to low-dose rate γ-radiation. Results from the late observation time points suggest that the hearts had mostly recovered from these two experimental conditions. However, further research is needed with larger numbers of animals for a more robust statistical power to fully characterize the early and late effects of simulated microgravity combined with exposure to low-dose rate ionizing radiation on the heart. PMID:28678877

A PILOT STUDY USING AN ACCELEROMETER TO EVALUATE A CAREGIVER'S INTERPRETATION OF AN INFANT OR TODDLER'S ACTIVITY LEVEL AS RECORDED IN A TIME ACTIVITY DIARY

EPA Science Inventory

Linking a young child's activity pattern data with samples that are collected during an exposure assessment is important in evaluating uptake dose rates associated with environmental contaminant exposures. A pilot study (N=9) was performed to test how well categorical activity-le...

Effects of prenatal exposure to a low dose atrazine metabolite mixture onpubertal timing and prostate development of male Long-Evans rats

EPA Science Inventory

Atrazine (ATR) is a chlorotriazine herbicide extensively used in the US and other countries. Studies examining the effects of adult or developmental ATR exposure on the mammary gland (MG) have used either the Sprague Dawley (SD) or Long-Evans (LE) rat, but no strain comparisons h...

Determination of the uncertainties in radiation doses from ingestion of strontium-90

NASA Astrophysics Data System (ADS)

Apostoaei, Andrei Iulian

Quantification of the uncertainties in the internal dosimetry is important because it can impact the outcome of dose reconstruction, risk assessment or epidemiological studies. This research focused on determination of the uncertainties in the dose factors from a single ingestion of 90Sr by adults, and analyzed the changes with age and the effect of gender. The uncertainties in the estimated dose factors are a factor of 6 for the bone surface, 5 for the red bone marrow, 2.5 for bladder and stomach, 2.2 for the small intestine, 2.1 for the upper large intestine and 2.7 for the lower large intestine. For the rest of the organs the uncertainty is a factor of 3. Only four parameters of the biokinetic model showed an age-dependency within the adult age group: the fractional transfers of strontium from plasma to cortical and trabecular bone, and the removal rates from the cortical and trabecular bone, respectively. When age-dependent biokinetic parameters were used, the estimated dose-factors are very close to the dose factors obtained using age-independent kinetics (within 40%). Thus, the dose factors based on age-independent parameters should suffice for most practical purposes. The dose factors and the associated uncertainties were also calculated as a function of age-at-exposure and attained age. These age dependent curves can be used for estimating doses from continuous intakes, or doses delivered over a limited portion of time. In addition to the committed dose, an expected dose is also estimated in this work. The expected dose is calculated using the dose rate weighted by the probability of surviving up to the age when the dose-rate is delivered. For exposure at young ages the expected dose and the committed dose are similar, but the committed dose decreases to zero when exposure occurs close to age 70, while the expected dose has elevated values pass age 70. No gender differences were found for bone surface, for red bone marrow, and the large intestine. The doses to the soft tissues for females are larger by 20% than the doses for males, because of the differences in the whole-body mass between males and females.