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Sample records for 90-day inhalation toxicity

  1. 90-Day Inhalation Toxicity Study of FT Fuel

    DTIC Science & Technology

    2011-08-01

    chromosome aberration test and micronucleus assay (Mattie et al., 2011a, 2011b), demonstrated that FT fuel was not mutagenic or genotoxic. The acute...over approximately 90 days, at concentrations of 0, 200, 700, and 2000 mg/m3. In the motor activity test , males exposed to the highest concentration...2 3.1 Test Substance ....................................................................................................................3 3.2

  2. Evaluation of the 90-Day Inhalation Toxicity of Petroleum and Oil Shale JP-5 Jet Fuel

    DTIC Science & Technology

    1985-04-01

    the required fill shall be rejected . If the number of defective or underfilled containers exceeds the acceptance number for ...035 The experiments reported herein were conducted according to the "Guide for the Care and Use of Laboratory Animals," Institute of Laboratory Animal...and is approved for publication. FOR THE COMMANDER BRUCE 0. STUART, PhD Director Toxic Hazards Division Air Force Aerospace Medical Research

  3. 90-Day Inhalation Toxicity Study of Swedish Biofuel Alcohol-to-Jet (ATJ) Synthetic Kerosene with Aromatics (SPA) in Rats with Neurotoxicity Testing and Genotoxicity Assay

    DTIC Science & Technology

    2015-09-01

    concentration in the 700 or 2000 mg/m3 exposure groups. No indications of changes in reproductive health were found when vaginal cytology and sperm...deemed biologically significant. As an indicator of reproductive health, vaginal cytology was assessed during week 9 of exposure and sperm count...endpoints assessed were neurotoxicity, reproductive toxicity, and genotoxicity. 4 Distribution Statement A. Approved for public release

  4. Subacute (90 days) oral toxicity studies of Kombucha tea.

    PubMed

    Vijayaraghavan, R; Singh, M; Rao, P V; Bhattacharya, R; Kumar, P; Sugendran, K; Kumar, O; Pant, S C; Singh, R

    2000-12-01

    Kombucha tea (KT) is a popular health beverage and is used as an alternative therapy. KT is prepared by placing the kombucha culture in solution of tea and sugar and allowing to ferment. The inoculum is a fungus consisting of symbiotic colony of yeast and bacteria. KT is consumed in several countries and is believed to have prophylactic and therapeutic benefits in a wide variety of ailments, viz., intestinal disorders, arthritis, ageing and stimulation of immunological system. Though KT is used in several parts of the world its beneficial effects and adverse effects have not been scientifically evaluated. Since there are no animal toxicological data on KT, subacute oral toxicity study was carried out. Five groups of rats were maintained: (a) control group given tap water orally, (b) KT given 2 ml/kg orally, (c) plain tea (PT) given 2 ml/kg orally, (d) KT given in drinking water, 1% (v/v) and (e) PT given in drinking water, 1% (v/v). The rats were given this treatment daily for a period of 90 days. Weekly records of weight, feed intake, water intake and general behaviour were monitored. There was no significant difference in the growth of the animals as evidenced by the progressive body weight change. The organ to body weight ratio and histological evaluation did not show any toxic signs. The haematological and biochemical variables were within the clinical limits. The study indicates that rats fed KT for 90 days showed no toxic effects.

  5. Evaluation of silica nanoparticle toxicity after topical exposure for 90 days

    PubMed Central

    Ryu, Hwa Jung; Seong, Nak-won; So, Byoung Joon; Seo, Heung-sik; Kim, Jun-ho; Hong, Jeong-Sup; Park, Myeong-kyu; Kim, Min-Seok; Kim, Yu-Ri; Cho, Kyu-Bong; Seo, Mu Yeb; Kim, Meyoung-Kon; Maeng, Eun Ho; Son, Sang Wook

    2014-01-01

    Silica is a very common material that can be found in both crystalline and amorphous forms. Well-known toxicities of the lung can occur after exposure to the crystalline form of silica. However, the toxicities of the amorphous form of silica have not been thoroughly studied. The majority of in vivo studies of amorphous silica nanoparticles (NPs) were performed using an inhalation exposure method. Since silica NPs can be commonly administered through the skin, a study of dermal silica toxicity was necessary to determine any harmful effects from dermal exposures. The present study focused on the results of systemic toxicity after applying 20 nm colloidal silica NPs on rat skin for 90 days, in accordance with the Organization for Economic Cooperation and Development test guideline 411 with a good laboratory practice system. Unlike the inhalation route or gastrointestinal route, the contact of silica NPs through skin did not result in any toxicity or any change in internal organs up to a dose of 2,000 mg/kg in rats. PMID:25565831

  6. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... target organs, body weight changes, effects on mortality and any other general or specific toxic effects... REQUIREMENTS Health Effects Test Guidelines § 799.9310 TSCA 90-day oral toxicity in rodents. (a) Scope. This... no-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure...

  7. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... target organs, body weight changes, effects on mortality and any other general or specific toxic effects... REQUIREMENTS Health Effects Test Guidelines § 799.9310 TSCA 90-day oral toxicity in rodents. (a) Scope. This... no-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure...

  8. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system...) Thyroids. (D) Respiratory system. (1) Trachea. (2) Lung. (3) Pharynx. (4) Larynx. (5) Nose. (E..., whatever its size, shape, and density. It is used to predict where in the respiratory tract such...

  9. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system...) Thyroids. (D) Respiratory system. (1) Trachea. (2) Lung. (3) Pharynx. (4) Larynx. (5) Nose. (E..., whatever its size, shape, and density. It is used to predict where in the respiratory tract such...

  10. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system...) Thyroids. (D) Respiratory system. (1) Trachea. (2) Lung. (3) Pharynx. (4) Larynx. (5) Nose. (E..., whatever its size, shape, and density. It is used to predict where in the respiratory tract such...

  11. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system...) Thyroids. (D) Respiratory system. (1) Trachea. (2) Lung. (3) Pharynx. (4) Larynx. (5) Nose. (E..., whatever its size, shape, and density. It is used to predict where in the respiratory tract such...

  12. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system...) Thyroids. (D) Respiratory system. (1) Trachea. (2) Lung. (3) Pharynx. (4) Larynx. (5) Nose. (E..., whatever its size, shape, and density. It is used to predict where in the respiratory tract such...

  13. Safety assessment of vitacoxib: Acute and 90-day sub-chronic oral toxicity studies.

    PubMed

    Wang, Jianzhong; Sun, Feifei; Tang, Shusheng; Zhang, Suxia; Lv, Pengyue; Li, Jing; Cao, Xingyuan

    2017-02-24

    Vitacoxib, is a newly developed coxibs NSAID (selective inhibitors of cyclooxygenase-2). To date, no experimental data have been published concerning its safety for use as an additive in the human diet. In the present study, we assessed the acute and sub-chronic toxicity of vitacoxib administered by gavage. The acute toxicity tests in Sprague Dawley (SD) rats and ICR mice demonstrated that vitacoxib at a dose of 5000 mg/kg BW failed to alter any of the parameters studied. In the 90-day sub-chronic toxicity test, vitacoxib was administered to SD rats at the doses of 0 (control), 5, 10, 20, 30, and 60 mg/kg BW. The results demonstrated that there were no significant differences for most indexes of sub-chronic toxicity throughout the experiment at the dose of 5-20 mg/kg BW, indicating no apparent dose-dependent. However, there were significant histopathology changes in the liver and kidney, and alterations in some biochemical parameters in the 60 mg/kg BW group. Based on these findings, the gavage LD50 was determined to be > 5000 mg/kg in SD rats and ICR mice, and the 90-day gavage no-observed-adverse-effect level (NOAEL) of vitacoxib was considered to be 20 mg/kg BW under the present study conditions.

  14. The 90-day oral toxicity of d-psicose in male Wistar rats.

    PubMed

    Matsuo, Tatsuhiro; Ishii, Reika; Shirai, Yoko

    2012-03-01

    d-Psicose is a rare sugar present in small quantities in natural products. In a previous study, we showed that d-psicose suppresses increase in plasma glucose and reduces body fat accumulation in rats. Based on acute toxicity testing in rats, d-psicose is classified as an ordinary substance (LD(50) = 16 g/kg). Elucidating the effects of sub-chronic feeding of d-psicose in rats is essential before it can be utilized as a physiologically functional food. In this study, male Wistar rats (3 weeks old) were fed diets containing 3% d-psicose or sucrose for 90 days. The body weight gain and intra-abdominal adipose tissue weight did not differ between the sucrose and the d-psicose groups. The weights of the liver and kidneys were significantly higher in the d-psicose group than in the sucrose group. However, no gross pathological findings were evident at dietary doses of 3% d-psicose or were correlated with hypertrophy of the liver and kidney. In a clinical chemistry analysis, the erythrocyte and leukocyte courts were significantly higher in the d-psicose group, but that was not considered to be toxicologically significant. Therefore, the present study found no adverse effects of d-psicose in rats fed a diet containing 3% d-psicosefor 90 days.

  15. A subchronic 90-day oral toxicity study of Origanum vulgare essential oil in rats.

    PubMed

    Llana-Ruiz-Cabello, M; Maisanaba, S; Puerto, M; Pichardo, S; Jos, A; Moyano, R; Cameán, A M

    2017-03-01

    Oregano essential oil (Origanum vulgare L. virens) (OEO) is being used in the food industry due to its useful properties to develop new active packaging systems. In this concern, the safety assessment of this natural extract is of great interest before being commercialized. The European Food Safety Authority requests different in vivo assays to ensure the safety of food contact materials. One of these studies is a 90 days repeated-dose oral assay in rodents. In the present work, 40 male and 40 female Wistar rats were orally exposed to 50, 100 and 200 mg/kg body weight (b.w.) OEO during 90 days following the OECD guideline 408. Data revealed no mortality and no treatment-related adverse effects of the OEO in food/water consumption, body weight, haematology, biochemistry, necropsy, organ weight and histopathology. These findings suggest that the oral no-observed-adverse-effect level (NOAEL) of this OEO is 200 mg/kg b.w. in Wistar rats, the highest dose tested. In conclusion, the use of this OEO in food packaging appears to be safe based on the lack of toxicity during the subchronic study at doses 330-fold higher than those expected to be in contact consumers in the worst scenario of exposure.

  16. A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats

    PubMed Central

    2012-01-01

    Background The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study. Methods In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250–3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments. Results DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count. Conclusions Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males. PMID:22892317

  17. Safety assessment of dietary bamboo charcoal powder: a 90-day subchronic oral toxicity and mutagenicity studies.

    PubMed

    Zhenchao, Jia; Yuting, Zhong; Jiuming, Yan; Yedan, Lu; Yang, Song; Jinyao, Chen; Lishi, Zhang

    2015-01-01

    Vegetable carbon has been used as food additive in EU (E153) and China for many years; however, no experimental data have been available on its dietary safety. This study was designed to evaluate the subchronic toxicity and genotoxicity of bamboo charcoal powder (BCP). In the study of subchronic oral toxicity, BCP was administered orally at doses of 2.81, 5.62, and 11.24 g/kg BW for 90 days to SD rats. Additional satellite groups from the control group and high dose group were observed for a 28-day recovery period. At the end of the treatment and recovery periods, animals were sacrificed, and their organs were weighed and blood samples were collected. The toxicological endpoints observed included clinical signs, food consumption, body and organ weights, hematological and biochemical parameters, macroscopic and microscopic examinations. The results showed no significant differences between the BCP treated groups and control group. The genotoxicity of BCP was assessed with the Salmonella typhimurium mutagenicity assay (Ames test) and a combination of comet assay and mammalian erythrocyte micronucleus protocol. The results did not reveal any genotoxicity of BCP. Based on our study, the no-observed-adverse-effect level (NOAEL) for BCP is 11.24 g/kg BW/day.

  18. A 90-day subchronic toxicity study of neem oil, a Azadirachta indica oil, in mice.

    PubMed

    Wang, C; Cao, M; Shi, D-X; Yin, Z-Q; Jia, R-Y; Wang, K-Y; Geng, Y; Wang, Y; Yao, X-P; Yang, Z-R; Zhao, J

    2013-09-01

    To determine the no-observed-adverse-effect level (NOAEL) of exposure and target organs of neem oil for establishing safety criteria for human exposure, the subchronic toxicity study with neem oil in mice was evaluated. The mice (10 per sex for each dose) was orally administered with neem oil with the doses of 0 (to serve as a control), 177, 533 and 1600 mg/kg/day for 90 days. After the treatment period, observation of reversibility or persistence of any toxic effects, mice were continuously fed without treatment for the following 30 days. During the two test periods, the serum biochemistry, organ weight and histopathology were examined. The results showed that the serum biochemistry and organ coefficient in experimental groups had no statistical difference compared with those of the control group. At the 90th day, the histopathological examinations showed that the 1600 mg/kg/day dose of neem oil had varying degrees of damage on each organ except heart, uterus and ovarian. After 30-day recovery, the degree of lesions to the tissues was lessened or even restored. The NOAEL of neem oil was 177 mg/kg/day for mice and the target organs of neem oil were determined to be testicle, liver and kidneys.

  19. [Kooroo color: 90-day dietary toxicity study in F344 rats].

    PubMed

    Sekita, Kiyoshi; Umemura, Takashi; Saito, Minoru; Ogawa, Yukio; Ueno, Katsunori; Kaneko, Toyozo; Uchida, Osayuki; Matsushima, Yuko; Kawasaki, Yasushi; Inoue, Tohru

    2002-06-01

    A subchronic toxicity study on kooroo color was conducted using F344 rats of both genders. Kooroo color is an extract of yam root, Dioscorea matudai Hayata, of which the major components are known to be flavonoid pigments. Use of kooroo as a food color is permitted by the Food Sanitation Law in Japan, but the chronic toxicity has not been evaluated in the literature. Rats were fed the product of kooroo color (PKC) at doses of 0.5%, 1.50%, and 5.0% in basal powder diet, while control groups received PKC-free basal diet, for ninety days. A vehicle control given propylene glycol (PG) alone, at the same dosage that the 5.0% group received, was included, because PKC used in this study contained ca. 80 percent PG, used as an extractant during the manufacturing processes. Daily observation of general behavior, and weekly measurement of body weight as well as food consumption were performed. Hematological, serum biochemical and anatomopathological examinations were conducted at the end of administration. No abnormalities ascribable to the treatment with PKC or PG were noted in any examination in this study. Hence, dietary intake of 5.0% of PKC, i.e., 2,993 mg/kg/day for males, and 3,376 mg/kg/day for females, as a mean daily intake for 90 days, had no observable adverse effect in F344 rats. Therefore, kooroo color has no significant general toxicity, and its toxicity, if any, is of a very low order.

  20. Toxicological assessment of a prototype e-cigaret device and three flavor formulations: a 90-day inhalation study in rats

    PubMed Central

    Werley, Michael S.; Kirkpatrick, Dan J.; Oldham, Michael J.; Jerome, Ann M.; Langston, Timothy B.; Lilly, Patrick D.; Smith, Donna C.; Mckinney, Willie J.

    2016-01-01

    Abstract A prototype electronic cigaret device and three formulations were evaluated in a 90-day rat inhalation study followed by a 42-day recovery period. Animals were randomly assigned to groups for exposure to low-, mid- and high-dose levels of aerosols composed of vehicle (glycerin and propylene glycol mixture); vehicle and 2.0% nicotine; or vehicle, 2.0% nicotine and flavor mixture. Daily targeted aerosol total particulate matter (TPM) doses of 3.2, 9.6 and 32.0 mg/kg/day were achieved by exposure to 1 mg/L aerosol for 16, 48 and 160 min, respectively. Pre-study evaluations included indirect ophthalmoscopy, virology and bacteriological screening. Body weights, clinical observations and food consumption were monitored weekly. Plasma nicotine and cotinine and carboxyhemoglobin levels were measured at days 28 and 90. After days 28, 56 and 90, lung function measurements were obtained. Biological endpoints after 90-day exposure and 42-day recovery period included clinical pathology, urinalysis, bronchoalveolar fluid (BALF) analysis, necropsy and histopathology. Treatment-related effects following 90 days of exposure included changes in body weight, food consumption and respiratory rate. Dose-related decreases in thymus and spleen weights, and increased BALF lactate dehydrogenase, total protein, alveolar macrophages, neutrophils and lung weights were observed. Histopathology evaluations revealed sporadic increases in nasal section 1–4 epithelial hyperplasia and vacuolization. Following the recovery period, effects in the nose and BALF were persistent while other effects were resolved. The no observed effect level based upon body weight decreases is considered to be the mid-dose level for each formulation, equivalent to a daily TPM exposure dose of approximately 9.6 mg/kg/day. PMID:26787428

  1. Toxicity of Carbon Nanotubes in the Lungs of Mice 7 and 90 Days After Intratracheal Instillation

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-Wing; James, John T.; McCluskey, Richard; Hunter, Robert L.

    2002-01-01

    Single-walled carbon nanotubes have many potential applications in the electronic, computer, and aerospace industries. Because unprocessed nanotubes could become airborne and potentially reach the lungs, their pulmonary toxicity was investigated. The three products studied were made by different methods, and contained different types and amounts of residual catalytic metals. Mice were each intratracheally instilled once with 0,0.1 or 0.5 mg of nanotubes, a carbon black negative control, or a quartz positive control, and killed for histopathological study 7 d or 90 d after the treatment. All nanotube products induced epithelioid granulomas and, in some cases, interstitial inflammation in the animals of the 7 -d groups. These lesions persisted and were worse in the 90-d groups. We found that, if nanotubes reach the lung, they can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.

  2. 90-day dietary toxicity study with esterified propoxylated glycerol (EPG) in micropigs.

    PubMed

    Wedig, John; Bechtel, David H

    2014-12-01

    The subchronic (90-day) toxicity of esterified propoxylated glycerol (EPG) was assessed in micropigs. Animals (5/sex/group) received feed containing 5%, 10%, and 17% EPG, mixed accordingly throughout the study to deliver 1.5, 3, and 5 g/kg bw/day of EPG, respectively. Corn oil served as the vehicle control (0 g/kg bw/day). Subsets of animals were evaluated at Week 6; the remainder between Weeks 12 and 14. With the exception of liver and serum vitamin levels, statistically significant difference between control and EPG groups were seen sporadically, and with no apparent connection to treatment and/or no consistency across time intervals. EPG intakes of 3 and 5 g/kg bw/day, but not at 1.5 g/kg bw/day were associated with significantly lower serum 25-OH vitamin D levels. Serum total vitamin D levels were significantly lower across all EPG groups. There were also trends toward lower levels of liver vitamins A and E among EPG-treated animals, but the effects were less consistent. The effects on vitamin levels observed in EPG-treated animals were not accompanied by any signs of vitamin deficiency (e.g., effects on growth, clinical signs, or clinical pathology), and might have been related to the larger mass of EPG acting as a lipid "sink" during transit in the gastrointestinal tract.

  3. Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats

    PubMed Central

    Ryu, Hwa Jung; Seo, Mu Yeb; Jung, Sung Kyu; Maeng, Eun Ho; Lee, Seung-Young; Jang, Dong-Hyouk; Lee, Taek-Jin; Jo, Ki-Yeon; Kim, Yu-Ri; Cho, Kyu-Bong; Kim, Meyoung-Kon; Lee, Beom Jun; Son, Sang Wook

    2014-01-01

    Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery) groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally. PMID:25565832

  4. A repeated dose 90-day oral toxicity study of cyflumetofen,a novel acaricide, in rats.

    PubMed

    Yoshida, Toshinori; Ikemi, Naoki; Takeuchi, Yukiko; Ebino, Koichi; Kojima, Sayuri; Chiba, Yuko; Nakashima, Nobuaki; Kawakatsu, Hisao; Saka, Machiko; Harada, Takanori

    2012-02-01

    Cyflumetofen is a novel acaricide which is highly active against phytophagous mites. As a part of safety assessment, a repeated dose 90-day oral toxicity study of cyflumetofen was conducted in Fischer (F344/DuCrj) rats of both sexes. Technical grade cyflumetofen was administered in feed to groups of 10 males and 10 females at dose levels of 0, 100, 300, 1,000, and 3,000 ppm. Prothrombin time was prolonged in males at 3,000 ppm and plasma globulin levels were decreased in females at 1,000 and 3,000 ppm. At necropsy, enlarged and whitish adrenals were observed in females at 3,000 ppm. There were statistically significant increases in relative liver weight (ratio to body weight) in males and relative adrenal weight in females in the 1,000 ppm group; increased relative liver and kidney weights in both sexes at 3,000 ppm, and increased absolute and relative weights of adrenals in females at 3,000 ppm. Increased absolute liver weight was also noted in males at 3,000 ppm. Histopathologically, at 1,000 and 3,000 ppm males had diffuse vacuolation and females had diffuse hypertrophy of adrenal cortical cells. In addition, vacuolation of ovarian interstitial gland cells was noted in females at 1,000 and 3,000 ppm. There were no treatment-related changes in any parameters for either sex in other dose groups. Based on these results, the no-observed-adverse-effect level (NOAEL) of cyflumetofen was judged to be 300 ppm for both sexes (16.5 mg/kg/day for males and 19.0 mg/kg/day for females).

  5. Evaluation of 90 day repeated dose oral toxicity and reproductive/developmental toxicity of 3'-hydroxypterostilbene in experimental animals

    PubMed Central

    Majeed, Muhammed; Bani, Sarang; Natarajan, Sankaran; Pandey, Anjali; S, Naveed

    2017-01-01

    3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium. Despite many proposed therapeutic applications, the safety profile of 3'-HPT has not been established. The present work investigated 90 day repeated oral dose and reproductive (developmental) toxicity of 3'-HPT as a test substance in rats as per OECD guidelines. 90 day toxicity was conducted in sixty Sprague Dawley rats of each sex (120 rats), grouped into six dosage groups of 0 (control), 0 (control recovery), 20 (low dose), 80 (mid dose), 200 (high dose) and 200 (high dose recovery) mg/kg bwt/day (body weight/day) respectively. For the reproductive toxicity study forty Wistar rats of each sex (80 rats) divided into four dosage groups received 0 (vehicle control), 20 (low dose), 100 (mid dose) and 200 (high dose) mg/kg bwt/day of 3'-HPT respectively for a period of two weeks while pre-mating, mating, on the day before sacrifice, in females during pregnancy and four days of lactation period. Results showed no significant differences in body weight, food intake, absolute organ weight, haematology, with no adverse effects (toxicity) on biochemical values nor any abnormal clinical signs or behavioural changes were observed in any of the control/treatment groups, including reproductive and developmental parameters, gross and histopathological changes. In conclusion, the results suggested a No-Observed-Adverse-Effect-Level (NOAEL) of 200 mg/kg bwt/day in rats after oral administration, implying 3'-HPT did not exhibit any toxicity under the study conditions employed. PMID:28257483

  6. Evaluation of 90 day repeated dose oral toxicity and reproductive/developmental toxicity of 3'-hydroxypterostilbene in experimental animals.

    PubMed

    Majeed, Muhammed; Bani, Sarang; Natarajan, Sankaran; Pandey, Anjali; S, Naveed

    2017-01-01

    3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium. Despite many proposed therapeutic applications, the safety profile of 3'-HPT has not been established. The present work investigated 90 day repeated oral dose and reproductive (developmental) toxicity of 3'-HPT as a test substance in rats as per OECD guidelines. 90 day toxicity was conducted in sixty Sprague Dawley rats of each sex (120 rats), grouped into six dosage groups of 0 (control), 0 (control recovery), 20 (low dose), 80 (mid dose), 200 (high dose) and 200 (high dose recovery) mg/kg bwt/day (body weight/day) respectively. For the reproductive toxicity study forty Wistar rats of each sex (80 rats) divided into four dosage groups received 0 (vehicle control), 20 (low dose), 100 (mid dose) and 200 (high dose) mg/kg bwt/day of 3'-HPT respectively for a period of two weeks while pre-mating, mating, on the day before sacrifice, in females during pregnancy and four days of lactation period. Results showed no significant differences in body weight, food intake, absolute organ weight, haematology, with no adverse effects (toxicity) on biochemical values nor any abnormal clinical signs or behavioural changes were observed in any of the control/treatment groups, including reproductive and developmental parameters, gross and histopathological changes. In conclusion, the results suggested a No-Observed-Adverse-Effect-Level (NOAEL) of 200 mg/kg bwt/day in rats after oral administration, implying 3'-HPT did not exhibit any toxicity under the study conditions employed.

  7. A 90-day toxicity study of GmTMT transgenic maize in Sprague-Dawley rats.

    PubMed

    Fang, Jin; Feng, Yongquan; Zhi, Yuan; Zhang, Lan; Yu, Zhou; Jia, Xudong

    2017-04-01

    GmTMT transgenic maize is a genetically modified maize plant that overexpresses the γ-tocopherol methyltransferase (γ-TMT) from Glycine max (Gm). The γ-TMT gene was introduced into maize line Zhen58 to encode the GmTMT2a protein which can convert γ-tocopherol into α-tocopherol. Overexpression of GmTMT2a significantly increased the α-tocopherol content in transgenic maize. The present study was designed to investigate any potential effects of GmTMT maize grain in a 90-day subchronic rodent feeding study. Maize grains from GmTMT or Zhen58 were incorporated into rodent diets at low (12.5%), medium (25%) or high (50%) concentrations and administered to Sprague-Dawley rats (n = 10/sex/group) for 90 days. The negative control group of rats (n = 10/sex/group) were fed with common maize diets. Results from body weights, feed consumption, clinical chemistry, hematology, absolute and relative organ weights indicated no treatment-related side effects of GmTMT maize grain on rats in comparison with rats consuming diets containing Zhen58 maize grain. In addition, no treatment-related changes were found in necropsy and histopathology examinations. Altogether, our data indicates that GmTMT transgenic maize is as safe and nutritious as its conventional non-transgenic maize.

  8. A 90-Day Oral Toxicity Study and a 5-Day Metabolism Study of Diisopropyl Methylphosphonate (DIMP) in Mink.

    DTIC Science & Technology

    1992-06-01

    Eighty 12-13 month-old brown "Ranch Wild " mink of each sex were randomized by body weight into eight dose groups of ten animals per sex. The animals...Laboratory Practice Standard (Toxic Substances Control Act) was followed. 90-DAY STUDY One hundred sixty 12-13 month-old brown "Ranch Wild " mink (80...3.2 x 10ŚM sec-’ * Hydrolysis Half- life : 687 years * Decomposition Products: (in microwave plasma discharge): methylphosphonic acid, isopropyl

  9. Safety assessment of essential oil from Minthostachys verticillata (Griseb.) Epling (peperina): 90-days oral subchronic toxicity study in rats.

    PubMed

    Escobar, Franco Matías; Sabini, María Carola; Cariddi, Laura Noelia; Sabini, Liliana Inés; Mañas, Fernando; Cristofolini, Andrea; Bagnis, Guillermo; Gallucci, Mauro Nicolas; Cavaglieri, Lilia Renée

    2015-02-01

    Minthostachys verticillata (Lamiaceae), popularly known as peperina is largely used in popular medicine for its digestive, carminative, antispasmodic and antirheumatic properties. There are no reports of repeated exposure toxicity to guarantee their safety. The present study investigated the chemical composition, analyzed by GC-FID, and the 90-day toxicity and genotoxicity effect of M. verticillata essential oil (Mv-EO), using Wistar rats as test animals. The rats were divided into four groups (5 rats/sex/group) and Mv-EO was administered on diet at doses of 0, 1, 4 and 7 g/kg feed. The main components of Mv-EO were pulegone (64.65%) and menthone (23.92%). There was no mortality, adverse effects on general conditions or changes in body weight, food consumption and feed conversion efficiency throughout the study in male and female rats. Subchronic administration of Mv-EO did not alter the weights, morphological and histopathological analyses of liver, kidney and intestine. Genotoxicity was tested by micronucleus and comet assays. Mv-EO up to a concentration of 7 g/kg feed for 90 days did not exert a cyto-genotoxic effect on the bone marrow and cells blood of Wistar rats. These results suggest that Mv-EO appears to be safe and could be devoid of any toxic risk.

  10. A 90-day oral (dietary) toxicity and mass balance study of corn starch fiber in Sprague Dawley rats.

    PubMed

    Crincoli, Christine M; Nikiforov, Andrey I; Rihner, Marisa O; Lambert, Elizabeth A; Greeley, Melanie A; Godsey, Justin; Eapen, Alex K; van de Ligt, Jennifer L G

    2016-11-01

    The potential toxicity of corn starch fiber was assessed and compared to polydextrose, a commonly used bulking agent with a long history of safe use in the food supply. Groups of male and female Crl:CD(SD) rats were fed 0 (control), 1,000, 3,000, or 10,000 mg/kg-bw/day corn starch fiber in the diet for 90 days. The polydextrose reference article was offered on a comparable regimen at 10,000 mg/kg-bw/day. Following a single gavage dose of [(14)C]-corn starch fiber on study day 13 or 90, the mass balance of the test article was assessed by analysis of excreta samples collected from 0 to 168 h post-dose. There were no toxicologically or biologically relevant findings in any of the test article-treated groups. The few minor differences observed between the corn starch fiber and polydextrose exposed groups were considered to be due to normal biological variation. Following [(14)C]-corn starch fiber dosing, nearly complete excretion of the administered dose occurred over 168 h post-dosing, with the majority excreted in the feces. The dietary no-observed-adverse-effect level of corn starch fiber after 90 days was 10,000 mg/kg-bw/day. Similar toxicity profiles for corn starch fiber and polydextrose were observed due to the structural and compositional similarities of these materials.

  11. A 90-day subchronic toxicity study with sodium formononetin-3'-sulphonate (Sul-F) delivered to dogs via intravenous administration.

    PubMed

    Li, Chunmei; Li, Guisheng; Gao, Yonglin; Sun, Chengfeng; Wang, Xiaoyan

    2016-06-01

    Sodium formononetin-3'-sulphonate (Sul-F) is a water-soluble derivate of formononetin, and an increasing number of studies have shown that Sul-F not only possesses favorable water solubility but also exhibits good lipid-lowering and bioactivities. In the current study, the toxicity of Sul-F was evaluated in dogs after 90-day intravenous infusion. Dogs were treated with Sul-F at dose of 0, 33.3, 100, and 300 mg/kg, and observed for 90-day followed by 28-day recovery period. Weekly measurement of body weight, temperature and food consumption were conducted. Ophthalmoscopy, ECG examination, urinalysis, serum biochemistry and hematology examination were performed at pre-test, on days 45 and 90, and following by 28-day recovery period. Histological examination was performed on day 90 and 28-day recovery period. No mortality, ophthalmic abnormalities or treatment-related findings in body weight, clinical chemistry, hematology, and histopathological examination were detected. However, a white crystal (non-metabolic Sul-F), transient vomiting and recoverable vascular stimulation were observed in 300 mg/kg/day Sul-F treated dogs. Under the conditions, the no-observed-adverse-effect-level (NOAEL) for Sul-F was 100 mg/kg in dogs.

  12. Pulmonary toxicity of simulated lunar and Martian dusts in mice: I. Histopathology 7 and 90 days after intratracheal instillation

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-Wing; James, John T.; McCluskey, Richard; Cowper, Shawn; Balis, John; Muro-Cacho, Carlos

    2002-01-01

    O(3) and MSS coexposure appeared to be more than additive. Results for the TiO(2) and quartz controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of lung injury was TiO(2) < LSS < MSS < O(3) + MSS < quartz. Except for TiO(2), the increased duration of dust presence in the lung from 7 to 90 days transformed the acute inflammatory response to a chronic inflammatory lesion. This study showed that LSS and MSS are more hazardous in the lungs than nuisance dusts.

  13. Pulmonary toxicity of simulated lunar and Martian dusts in mice: I. Histopathology 7 and 90 days after intratracheal instillation.

    PubMed

    Lam, Chiu-Wing; James, John T; McCluskey, Richard; Cowper, Shawn; Balis, John; Muro-Cacho, Carlos

    2002-09-01

    O(3) and MSS coexposure appeared to be more than additive. Results for the TiO(2) and quartz controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of lung injury was TiO(2) < LSS < MSS < O(3) + MSS < quartz. Except for TiO(2), the increased duration of dust presence in the lung from 7 to 90 days transformed the acute inflammatory response to a chronic inflammatory lesion. This study showed that LSS and MSS are more hazardous in the lungs than nuisance dusts.

  14. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-Wing; James, John T.; McCluskey, Richard; Hunter, Robert L.

    2004-01-01

    Nanomaterials are part of an industrial revolution to develop lightweight but strong materials for a variety of purposes. Single-wall carbon nanotubes are an important member of this class of materials. They structurally resemble rolled-up graphite sheets, usually with one end capped; individually they are about 1 nm in diameter and several microns long, but they often pack tightly together to form rods or ropes of microscopic sizes. Carbon nanotubes possess unique electrical, mechanical, and thermal properties and have many potential applications in the electronics, computer, and aerospace industries. Unprocessed nanotubes are very light and could become airborne and potentially reach the lungs. Because the toxicity of nanotubes in the lung is not known, their pulmonary toxicity was investigated. The three products studied were made by different methods and contained different types and amounts of residual catalytic metals. Mice were intratracheally instilled with 0, 0.1, or 0.5 mg of carbon nanotubes, a carbon black negative control, or a quartz positive control and euthanized 7 d or 90 d after the single treatment for histopathological study of the lungs. All nanotube products induced dose-dependent epithelioid granulomas and, in some cases, interstitial inflammation in the animals of the 7-d groups. These lesions persisted and were more pronounced in the 90-d groups; the lungs of some animals also revealed peribronchial inflammation and necrosis that had extended into the alveolar septa. The lungs of mice treated with carbon black were normal, whereas those treated with high-dose quartz revealed mild to moderate inflammation. These results show that, for the test conditions described here and on an equal-weight basis, if carbon nanotubes reach the lungs, they are much more toxic than carbon black and can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.

  15. Evaluation of 90-Day Inhalation Toxicity of Petroleum and Oil Shale Diesel Fuel Marine (DFM)

    DTIC Science & Technology

    1985-12-01

    ileum, kidneys, larynx, liver, lungs and bronchi, mammary gland, mesenteric and mandibular lymph nodes, nasal cavity, ovaries, pancreas, parathyroids...Virtually all of the male rats exposed to 300 mg/M 3 had mineralized deposits in the renal papilla . The incidence of mineralization in male rats exposed to...demonstrated mineralization of the renal papilla . The severity of this lesion was characterized as mild, with no indication of a dose related increase in

  16. Toxicity studies on agent GA (Phase 2): 90 day subchronic study of GA (Tabun) in cd rats. Appendices. Final report, July 1985-August 1991

    SciTech Connect

    Not Available

    1992-03-01

    The purpose of the report is to provide essential toxicologic information on Tabun administration over a 90 day period. This toxicologic information may be used to adjust the maximum-tolerated dose for subsequent dominant-lethal and two-generation reproduction studies. The objectives were to determine the toxic effects of nerve agent exposure (e.g., target organs); and to determine the effects of nerve agent GA on sperm morphology and motility and vaginal cytology.

  17. 90-Day Cycle Handbook

    ERIC Educational Resources Information Center

    Park, Sandra; Takahashi, Sola

    2013-01-01

    90-Day Cycles are a disciplined and structured form of inquiry designed to produce and test knowledge syntheses, prototyped processes, or products in support of improvement work. With any type of activity, organizations inevitably encounter roadblocks to improving performance and outcomes. These barriers might include intractable problems at…

  18. Evaluation of the Tobacco Heating System 2.2. Part 6: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects of a mentholated version compared with mentholated and non-mentholated cigarette smoke.

    PubMed

    Oviedo, Alberto; Lebrun, Stefan; Kogel, Ulrike; Ho, Jenny; Tan, Wei Teck; Titz, Bjoern; Leroy, Patrice; Vuillaume, Gregory; Bera, Monali; Martin, Florian; Rodrigo, Gregory; Esposito, Marco; Dempsey, Ruth; Ivanov, Nikolai V; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

    2016-11-30

    The toxicity of a mentholated version of the Tobacco Heating System (THS2.2M), a candidate modified risk tobacco product (MRTP), was characterized in a 90-day OECD inhalation study. Differential gene and protein expression analysis of nasal epithelium and lung tissue was also performed to record exposure effects at the molecular level. Rats were exposed to filtered air (sham), to THS2.2M (at 15, 23 and 50 μg nicotine/l), to two mentholated reference cigarettes (MRC) (at 23 μg nicotine/l), or to the 3R4F reference cigarette (at 23 μg nicotine/l). MRCs were designed to meet 3R4F specifications. Test atmosphere analyses demonstrated that aldehydes were reduced by 75%-90% and carbon monoxide by 98% in THS2.2M aerosol compared with MRC smoke; aerosol uptake was confirmed by carboxyhemoglobin and menthol concentrations in blood, and by the quantities of urinary nicotine metabolites. Systemic toxicity and alterations in the respiratory tract were significantly lower in THS2.2M-exposed rats compared with MRC and 3R4F. Pulmonary inflammation and the magnitude of the changes in gene and protein expression were also dramatically lower after THS2.2M exposure compared with MRCs and 3R4F. No menthol-related effects were observed after MRC mainstream smoke-exposure compared with 3R4F.

  19. Evaluation of the Tobacco Heating System 2.2. Part 4: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects compared with cigarette smoke.

    PubMed

    Wong, Ee Tsin; Kogel, Ulrike; Veljkovic, Emilija; Martin, Florian; Xiang, Yang; Boue, Stephanie; Vuillaume, Gregory; Leroy, Patrice; Guedj, Emmanuel; Rodrigo, Gregory; Ivanov, Nikolai V; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

    2016-11-30

    The objective of the study was to characterize the toxicity from sub-chronic inhalation of test atmospheres from the candidate modified risk tobacco product (MRTP), Tobacco Heating System version 2.2 (THS2.2), and to compare it with that of the 3R4F reference cigarette. A 90-day nose-only inhalation study on Sprague-Dawley rats was performed, combining classical and systems toxicology approaches. Reduction in respiratory minute volume, degree of lung inflammation, and histopathological findings in the respiratory tract organs were significantly less pronounced in THS2.2-exposed groups compared with 3R4F-exposed groups. Transcriptomics data obtained from nasal epithelium and lung parenchyma showed concentration-dependent differential gene expression following 3R4F exposure that was less pronounced in the THS2.2-exposed groups. Molecular network analysis showed that inflammatory processes were the most affected by 3R4F, while the extent of THS2.2 impact was much lower. Most other toxicological endpoints evaluated did not show exposure-related effects. Where findings were observed, the effects were similar in 3R4F- and THS2.2-exposed animals. In summary, toxicological changes observed in the respiratory tract organs of THS2.2 aerosol-exposed rats were much less pronounced than in 3R4F-exposed rats while other toxicological endpoints either showed no exposure-related effects or were comparable to what was observed in the 3R4F-exposed rats.

  20. Safety assessment of the fermented Phylloporia ribis (Lonicera japonica Thunb.) mycelia by oral acute toxicity study in mice and 90-day feeding study in rats.

    PubMed

    Lu, Lianhua; Fan, Yiou; Yao, Wenhuan; Xie, Wei; Guo, Jie; Yan, Yan; Yang, Fei; Xu, Lingchuan

    2014-07-01

    Phylloporia ribis is an edible fungus in China. Its fermented mycelia have been approved by the National Health and Family Planning Commission (NHFPC) of PR China for use as a novel food material, but little information on its safety is available. The present research was the first to evaluate acute and subchronic toxicity in experimental animals of fermented Phylloporia ribis mycelia (FPM) following standard procedures. In acute toxicity study, FPM was orally administered to male and female mice twice a day at single dose of 10 g/kg bw. The Maximum Tolerated Dose (MTD) of FPM for mice of both sexes was over 10 g/kg bw. No death and abnormal behaviors occurred during 14 days study except for an increased locomotor activity in three animals. In 90-day feeding study, male and female Sprague-Dawley rats were fed diets containing 10.0%, 5.0%, 2.5%, 1.25% and 0% (control) FPM for 90 days. The treatment caused no effects on mortality, gross pathology, histology, hematology, and blood chemistry, no dose-dependent changes in food consumption, but caused effect on body weight gain compared with control group. The No Observed Adverse-Effect Level (NOAEL) of FPM was greater than 8.7 g/kg bw/day in both sexes of rats.

  1. Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats.

    PubMed

    Feng, Weiwei; Wu, Huiyu; Li, Qian; Zhou, Zhaoxiang; Chen, Yao; Zhao, Ting; Feng, Yun; Mao, Guanghua; Li, Fang; Yang, Liuqing; Wu, Xiangyang

    2015-11-01

    Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption.

  2. A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats

    PubMed Central

    Park, Hark-Soo; Kim, Seon-Ju; Lee, Taek-Jin; Kim, Geon-Yong; Meang, EunHo; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Hong, Seung-Guk; Sun, Yle-Shik; Kang, Jin Seok; Kim, Yu-Ri; Kim, Meyoung-Kon; Jeong, Jayoung; Lee, Jong-Kwon; Son, Woo-Chan; Park, Jae-Hak

    2014-01-01

    Purpose The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM20(+)) nanoparticles in Sprague Dawley rats for 90 days. Methods For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg) and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM20(+) NPs. Results No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with control in both 500 mg/kg groups. Total protein and albumin levels were decreased significantly in both sexes in the 250 and 500 mg/kg groups. Histopathological studies revealed acinar cell apoptosis in the pancreas, inflammation and edema in stomach mucosa, and retinal atrophy of the eye in the 500 mg/kg group. Conclusion There were significant parameter changes in terms of anemia in the hematological and blood chemical analyses in the 250 and 500 mg/kg groups. The significant toxic change was observed to be below 125 mg/kg, so the no-observed-adverse-effect level was not determined, but the lowest-observed-adverse-effect level was considered to be 125 mg/kg in both sexes and the target organs were found to be the pancreas, eye, and stomach. PMID:25565829

  3. Safety assessment of freeze-dried powdered Tenebrio molitor larvae (yellow mealworm) as novel food source: Evaluation of 90-day toxicity in Sprague-Dawley rats.

    PubMed

    Han, So-Ri; Lee, Byoung-Seok; Jung, Kyung-Jin; Yu, Hee-Jin; Yun, Eun-Young; Hwang, Jae Sam; Moon, Kyoung-Sik

    2016-06-01

    Worldwide demand for novel food source has grown and edible insects are a promising food sources for humans. Tenebrio molitor, as known as yellow mealworm, has advantages of being rich in protein, and easy to raise as a novel food source. The objective of this study was to evaluate subchronic toxicity, including potential hypersensitivity, of freeze-dried powdered T. molitor larvae (fdTML) in male and female Sprague-Dawley rats. The fdTML was administered orally once daily at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 90 days. A toxicological assessment was performed, which included mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings, histopathologic examination and allergic reaction. There were no fdTML- related findings in clinical signs, urinalysis, hematology and serum chemistry, gross examination, histopathologic examination or allergic reaction. In conclusion, the No Observed Adverse Effect Level (NOAEL) for fdTML was determined to be in excess of 3000 mg/kg/day in both sexes of rats under the experimental conditions of this study.

  4. A 90-day repeated dose oral (gavage) toxicity study of perfluorohexanoic acid (PFHxA) in rats (with functional observational battery and motor activity determinations).

    PubMed

    Chengelis, Christopher P; Kirkpatrick, Jeannie B; Radovsky, Ann; Shinohara, Motoki

    2009-06-01

    Possible toxic effects of perfluorohexanoic acid (PFHxA) were evaluated when administered orally by gavage to rats at levels up to 200mg/kg/day for 90 days. Lower body weight gains were noted in the 10, 50 and 200mg/kg/day group males (not dose-responsive) throughout dosing. Other changes included lower red blood cell parameters, higher reticulocyte counts and lower globulin in the 200mg/kg/day group males and females, higher liver enzymes in males at 50 and 200mg/kg/day, lower total protein and higher albumin/globulin ratio, and lower cholesterol, calcium in males at 200mg/kg/day. Minimal centrilobular hepatocellular hypertrophy was present in 200mg/kg/day group males and correlated with higher liver weights and slightly higher peroxisome beta oxidation activity at the end of the dosing period. Based on liver histopathology and liver weight changes, the no-observed-adverse-effect level (NOAEL) for oral administration was 50mg/kg/day for males and 200mg/kg/day for females.

  5. Toxicity studies on Agents GB and GD (Phase 2): 90-day subchronic study of GB (Sarin, Type II) in CD rats. Final report, Jul 85-Aug 91

    SciTech Connect

    Bucci, T.J.; Parker, R.M.

    1992-01-01

    A two-phase Dose Range findng study and a 90-Day Subchronic study were conducted in CD rats using the organophosphate ester Sarin (Agent GB, Type II, CAS Number 107-44-8). The highest dose level without lethality in the second phase of the range finding study was designated the maximum tolerated dose (MTD). The doses selected for the subchronic study were the MTD (300 micron GBII/Kg/day), MTD/2 (150micron GBII/Kg/day), MTD/4 (75micron GBII/Kg/day), and a vehicle control . Forty-eight male and forty-eight female CD rats were randomly allocated at 11 -1 2 weeks of age into four treatment groups (1 2 per sex per group). The animals were gavaged Monday through Friday for 13 weeks and euthanized with carbon dioxide at the beginning of the fourteenth week. Animals were observed daily for clinical signs of toxicity and were weighed weekly. The rats were bled (6 rat/sex/dose) during weeks -1, 1, 3, 7, and at necropsy. Necropsy examination was performed on all animals. Microscopic evaluation was performed on all high-dose and control animals and on those tissues of lower dose animals that were abnormal at necropsy. All gross lesions and all animals dying or removed early received histological examination. A cause of death or morbidity for animals removed before the end of the study, determined from histopathological examination, was established in four cases. There were several statistically significant effects in the clinical chemistry and hematology data. These effects were scattered among the treatment groups and were not numerous enough to develop a pattern of organ toxicity.

  6. Toxicity studies on Agents GB and GD (Phase 2): 90-day subchronic study of GB (Sarin, Type I) in CD rats. Final report, Jul 85-Aug 91

    SciTech Connect

    Bucci, T.J.; Parker, R.M.; Crowell, J.A.; Thurman, J.D.; Gosnell, P.A.

    1991-08-01

    A two-phase Dose Range finding study and a 90-Day Subchronic study were conducted in CD rats using the organophosphate ester Sarin (Agent GB, Type I, CAS Number 107-44-8). The highest dose level without lethality in the second phase of the range finding study was designated the maximum tolerated dose (MTD). The doses selected for the subchronic study were the MTD (300 micron GBI/Kg/day), MTD/2 (150, micron GBI/Kg/day), MTD/4 (75 micron GBI/Kg/day), and a vehicle control (O micron /Kg/day). Forty-eight male and forty-eight female CD rats were randomly allocated at 11-12 weeks of age into four treatment groups (12 per sex per group). The animals were gavaged Monday through Friday for 13 weeks and euthanized with carbon dioxide at the beginning of the fourteenth week. Animals were observed daily for clinical signs of toxicity and were weighed weekly. The rats were bled (6 rats/sex/dose) during weeks -1, 1, 3, 7, and at necropsy. Necropsy examination was performed on all animals. Microscopic evaluation was performed on all high-dose and control animals, and on those tissues of lower dose animals that were abnormal at necropsy. All gross lesions and all animals dying or removed early received histological examination. A cause of death or morbidity for animals removed before the end of the study, determined from histopathological examination, was established in four of the eight cases. There were several statistically significant effects in the clinical chemistry and hematology data. These effects were scattered among the treatment groups and were not numerous enough to develop a pattern of organ toxicity.

  7. Results of a 90-day toxicity study on 1,2,3- and 1,1,2-trichloropropane administered via the drinking water.

    PubMed

    Villeneuve, D C; Chu, I; Secours, V E; Coté, M G; Plaa, G L; Valli, V E

    1985-12-01

    Trichloropropanes have been identified as environmental contaminants in sediments of the Great Lakes region of North America. Since these chemicals had the potential to find their way into drinking water, a 90-day feeding study was carried out in order to determine their subchronic toxicity. Groups of 10 male and 10 female weanling Sprague-Dawley rats were supplied drinking water ad libitum, containing 1,2,3- or 1,1,2-trichloropropane at concentrations of 1, 10, 100 or 1000 mg/L for 13 weeks. Emulphor (0.5%) was used to solubilize the chemicals. At the end of the study, the animals were killed and examined for gross and microscopic changes. Heart, liver, brain, kidney and spleen were excised and weighed. Blood was collected and subjected to a comprehensive hematological analysis. Serum was collected and profiled for changes in 12 biochemical parameters and a portion of liver was used to determined mixed function oxidase activity. Although three animals died during the study, their deaths could not be related to treatment. Decreased growth rate was observed in both sexes of the group receiving 1000 mg/L 1,2,3-trichloropropane. There was an increase in liver, kidney and brain weights (relative to body weight) in rats of both sexes fed 1000 mg/L 1,2,3-trichloropropane. Fatty livers were observed in some of the treated animals but a clear dose-relationship was not evident. An elevation in serum cholesterol was observed in female rats fed the highest dose of 1,2,3-trichloropropane.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. 90-Day Nose-Only Inhalation Toxicity Study of Trifluoroiodomethane (CG3I) to Male and Female Fischer Rats

    DTIC Science & Technology

    1996-02-01

    or 8% CF3I, minimal to mild atrophy of the testes and degeneration of spermatogonia in male rats exposed to 4 or 8% CF3I, and a mild m increase in...parameters included erythrocyte (RBC), leukocyte (WBC), differential leukocyte and platelet counts, hemoglobin (HGB), hematocrit (HCT), mean corpuscular... differentials were determined according to established procedures. Erythrocytes were enumerated on a Coulter counter (Coulter Electronics, Hialeah, FL

  9. Metabonomics study of transgenic Bacillus thuringiensis rice (T2A-1) meal in a 90-day dietary toxicity study in rats.

    PubMed

    Cao, Sishuo; Xu, Wentao; Luo, YunBo; He, Xiaoyun; Yuan, Yanfang; Ran, Wenjun; Liang, Lixing; Huang, Kunlun

    2011-07-01

    Rice is one of the most important staple foods in the world. The Cry2A gene was inserted into the rice genome to help the plant combat insects. As the unintended effects of the genetically modified (GM) organisms are the most important barriers to the promotion of GM organisms, we have carried out a useful exploration to establish a new in vivo evaluation model for genetically modified foods by metabonomics methods. In this study, the rats were fed for 90 days with the GM and NON-GM rice diets. The changes in metabolites of the urine were detected using (1)H-NMR. The metabonomics were analyzed to see whether the GM rice can induce the metabolite changes in the rats' urine when compared with the NON-GM rice group. The multivariate analysis and ANOVA were used to determine the differences and the significance of differences respectively, and eventually we concluded that these differences did not have a biological significance. The conclusion of the metabonomics was comparable with that from the traditional method. As a non-invasive and dynamic monitoring method, metabonomics will be a new way of assessing the food safety of GM foods.

  10. Assessment of the safety of hydrogenated resistant maltodextrin: reverse mutation assay, acute and 90-day subchronic repeated oral toxicity in rats, and acute no-effect level for diarrhea in humans.

    PubMed

    Yoshikawa, Yuko; Kishimoto, Yuka; Tagami, Hiroyuki; Kanahori, Sumiko

    2013-01-01

    A series of safety assessments were performed on hydrogenated resistant maltodextrin prepared by converting the reducing terminal glucose of resistant maltodextrin into sorbitol. The reverse mutation assay did not show mutagenicity. Acute and 90-day subchronic oral toxicity studies in rats showed no death was observed in any groups, including the group receiving the highest single dose of 10 g/kg body weight or the highest dose of 5 g/kg body weight per day for 90 days. Mucous or watery stools were observed in the hydrogenated resistant maltodextrin treatment group on the acute study, which were transient and were associated with the osmotic pressure caused by intake of the high concentrations. Subchronic study showed dose-dependent increases in the weights of cecum alone, cecal contents alone, and cecum with cecal contents as well as hypertrophy of the cecal mucosal epithelium, which are considered to be common physiological responses after intake of indigestible carbohydrates. These results indicated that the no observed adverse effect level (NOAEL) of hydrogenated resistant maltodextrin was 10 g/kg body weight or more on the acute oral toxicity study and 5.0 g/kg body weight/day or more on the 90-day subchronic repeated oral toxicity study in rats. Further study performed in healthy adult humans showed that the acute no-effect level of hydrogenated resistant maltodextrin for diarrhea was 0.8 g/kg body weight for men and more than 1.0 g/kg body weight for women. The results of the current safety assessment studies suggest that hydrogenated resistant maltodextrin is safe for human consumption.

  11. Studies on the Inhalation Toxicity of Dyes Present in Colored Smoke Munitions. Phase IV. 90-Day Inhalation Exposures of Rats to Dye Aerosols

    DTIC Science & Technology

    1985-10-01

    epithelial cell hyperplasla and proliferation of foamy alveolar •. macrophages and lymphoid hyperplasia in the tracheobronchial lymph nodes of rats exposed...These accumulations of alveolar macrophages were accompanied by slight to moderate hyperplasia of k Type II cells (granular pneumocytes). In the nasal...dose rats. These accumulations of alveolar macrophages were accompanied by slight to moderate hyperplasii of Type II cells (granular pneumocytes). In the

  12. Subacute Inhalation Toxicity of 3-Methylpentane

    PubMed Central

    Chung, Yong Hyun; Shin, Seo-Ho; Han, Jeong Hee; Lee, Yong-Hoon

    2016-01-01

    3-Methylpentane (C6H14, CAS No. 96-14-0), isomer of hexane, is a colorless liquid originating naturally from petroleum or natural gas liquids. 3-Methylpentane has been used as a solvent in organic synthesis, as a lubricant, and as a raw material for producing carbon black. There is limited information available on the inhalation toxicity of 3-methylpentane, and the aim of this study was to determine its subacute inhalation toxicity. According to OECD Test Guideline 412 (subacute inhalation toxicity: 28-day study), Sprague Dawley rats were exposed to 0, 284, 1,135, and 4,540 ppm of 3-methylpentane for 6 hr/day, 5 days/week for 4 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, organ weights, and gross and histopathological findings were compared between control and all exposure groups. No mortality or remarkable clinical signs were observed during the study. No gross or histopathological lesions, or adverse effects on body weight, food consumption, hematology, serum chemistry, and organ weights were observed in any male or female rats in all exposure groups, although some statistically significant changes were observed in food consumption, serum chemistry, and organ weights. In conclusion, the results of this study indicate that no observable adverse effect level (NOAEL) for 3-methylpentane above 4,540 ppm/6 hr/day, 5 days/week for rats. PMID:27437092

  13. Inhalation toxicity of methyl difluoromalonyl fluoride in rats

    SciTech Connect

    Kennedy, G.L. Jr.; Burgess, B.A.; Chen, H.C.

    1988-06-01

    Methyl 2,2-difluoromalonyl fluoride (MMF) is highly toxic by inhalation producing mortality in rats exposed for 4 hours to 0.55 mg/L. Repeated inhalation exposures of rats to 0.009 mg/L produced irritation but no other signs of a toxic response. Mortality was encountered following repeated exposures to 0.066 mg/L.

  14. 90-Day Inhalation Toxicity Study of Hydroprocessed Esters and Fatty Acids (HEFA) Bio-Based Jet Fuel in Rats (Rattus norvegicus) with Neurotoxicity Testing and Genotoxicity Assay

    DTIC Science & Technology

    2013-06-01

    nociception , social interaction, the forced swim test, spontaneous locomotor activity, passive avoidance or Morris water maze performance. However...system. V.4. Technical Methods V.4.1. Pain / Distress Assessment V.4.1.1. APHIS Form 7023 Information V.4.1.1.1. Number of Animals V...4.1.1.1.1. Column C: 0 V.4.1.1.1.2. Column D: 150 V.4.1.1.1.3. Column E: 0 V.4.1.2. Pain Relief / Prevention V.4.1.2.1. Anesthesia

  15. 90-Day Inhalation Toxicity Study of Bio-Derived Gevo Alcohol-to-Jet (ATJ) Synthetic Paraffinic Kerosene (SPK) in Rats with Neurotoxicity Testing and Genotoxicity Assay

    DTIC Science & Technology

    2015-05-31

    Animals were fed a certified rodent diet (Formulab Diet Purina Lab Chow, PMI Nutrition, International, LLC, Brentwood MO), ad libitum, except during...weights of the liver , kidneys, adrenals, testes, epididymides, ovaries, uterus, thymus, spleen, brain, and heart were obtained after dissection from the...g) 0.02 0.01 0.02 0.02 % BW (mean) 0.02 0.02 0.02 0.02 % BW (SD) 0.01 0.005 0.005 0.01 Liver Average (g) 10.15a 10.51 9.98 10.89 SD (g) 0.46a

  16. The Toxicity of Inhaled Sulphur Mustard

    DTIC Science & Technology

    2012-03-01

    acetyl -L- cysteine (Mucomyst™; NAC ), in ameliorating inhaled HD-induced lung injury was then assessed in the established model. This work was conducted...J and Sciuto AM. N- acetyl -L- cysteine ( NAC ) Protects Against Inhaled Sulfur Mustard (HD) Poisoning in the Large Swine. Clinical Toxicology, 2012...2012. N- acetyl -L- cysteine ( NAC ) Protects against inhaled sulfur mustard (HD) poisoning in the large swine. Clinical Toxicology; in preparation

  17. The subacute inhalation toxicity of 109 industrial chemicals

    PubMed Central

    Gage, J. C.

    1970-01-01

    Gage, J. C. (1970).Brit. J. industr. Med.,27, 1-18. The subacute inhalation toxicity of 109 industrial chemicals. The inhalation toxicity of 109 substances has been studied by exposing experimental animals to known concentrations in air for periods of about three weeks. The toxic properties of these substances are reviewed in relation to the effects of similar compounds on animals and on man. Provisional operational limits are suggested to assist in the design of new plant and in the establishment of codes for safe manufacturing practice. PMID:5418916

  18. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... respiratory tract such particles may be deposited. This term is used in contrast to measured or geometric... within the respiratory tract. (3) The geometric mean diameter or the median diameter is the calculated... respiratory tract from the trachea to the alveoli. For man, inhalable diameter is considered as 15...

  19. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... respiratory tract such particles may be deposited. This term is used in contrast to measured or geometric... within the respiratory tract. (3) The geometric mean diameter or the median diameter is the calculated... respiratory tract from the trachea to the alveoli. For man, inhalable diameter is considered as 15...

  20. Toxicological assessment of kretek cigarettes. Part 7: the impact of ingredients added to kretek cigarettes on inhalation toxicity.

    PubMed

    Schramke, H; Roemer, E; Dempsey, R; Hirter, J; Meurrens, K; Berges, A; Weiler, H; Vanscheeuwijck, P; Schorp, M K

    2014-12-01

    The biological activity of mainstream smoke from experimental kretek cigarettes with and without three mixes of ingredients was assessed in a 90-day rat inhalation study and in a 4-day in vivo micronucleus assay. 350 ingredients, commonly used in various combinations and in a limited number in a given brand in the manufacture of marketed kretek cigarettes, were applied at a low and a high target level to test cigarettes with a typical Indonesian blend of tobaccos and cloves. In the 90-day inhalation study, effects commonly seen in rat inhalation studies with mainstream smoke were observed. In general, no ingredients-related histopathological changes were found in the respiratory tract. In the 4-day micronucleus assay exposure of male rats to mainstream smoke from the test cigarettes containing any of the three mixes did not increase the proportions of micronucleated cells in peripheral blood and bone marrow over the proportion of micronucleated cells in the control group. Based on the results of these studies, it can be concluded that the addition of ingredients commonly used in the manufacture of kretek cigarettes did not change the overall in vivo toxicity profile of the mainstream smoke.

  1. Toxic alveolitis after inhalation of a water repellent.

    PubMed

    Epping, Guido; Van Baarlen, Joop; Van Der Valk, Paul D L P M

    2011-12-01

    Inhalation of fluorocarbon polymers can cause pulmonary toxicity. Although multiple cases of lung injury have been reported, cellular characterization of the associated alveolitis occurring acutely after inhalation is limited. We report the case of a previously healthy woman who presented at our Emergency Department with an acute pneumonitis following inhalation of a fluorocarbon polymer-based rain-proofing spray. Bronchoalveolar lavage (BAL) performed shortly after the presentation showed an elevated total cell count, with a high proportion of neutrophils (58%) and eosinophils (9%). In addition, a lipid stain (Oil-Red-O-stain) showed a high level of lipid laden macrophages, a marker that could reflect a direct toxic effect of the spray on alveolar cells. The patient made a full recovery after four days of in-hospital observation with supportive care.

  2. 40 CFR 798.4350 - Inhalation developmental toxicity study.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... to ensure that conditions throughout the exposure chamber are essentially the same. Test material... of the toxic characteristics of an inhalable material such as a gas, volatile substance, or aerosol... particles of the test substance. It is used to compare particles of different sizes, shapes, and...

  3. 40 CFR 798.4350 - Inhalation developmental toxicity study.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... to ensure that conditions throughout the exposure chamber are essentially the same. Test material... of the toxic characteristics of an inhalable material such as a gas, volatile substance, or aerosol... particles of the test substance. It is used to compare particles of different sizes, shapes, and...

  4. 40 CFR 798.4350 - Inhalation developmental toxicity study.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... to ensure that conditions throughout the exposure chamber are essentially the same. Test material... of the toxic characteristics of an inhalable material such as a gas, volatile substance, or aerosol... particles of the test substance. It is used to compare particles of different sizes, shapes, and...

  5. The toxicity of inhaled methanol vapors

    SciTech Connect

    Kavet, R.; Nauss, K.M. )

    1990-01-01

    Methanol could become a major automotive fuel in the U.S., and its use may result in increased exposure of the public to methanol vapor. Nearly all of the available information on methanol toxicity in humans relates to the consequences of acute, rather than chronic, exposures. Acute methanol toxicity evolves in a well-understood pattern and consists of an uncompensated metabolic acidosis with superimposed toxicity to the visual system. The toxic properties of methanol are rooted in the factors that govern both the conversion of methanol to formic acid and the subsequent metabolism of formate to carbon dioxide in the folate pathway. In short, the toxic syndrome sets in if formate generation continues at a rate that exceeds its rate of metabolism. Current evidence indicates that formate accumulation will not challenge the metabolic capacity of the folate pathway at the anticipated levels of exposure to automotive methanol vapor.117 references.

  6. Pulmonary toxicity of printer toner following inhalation and intratracheal instillation.

    PubMed

    Morimoto, Yasuo; Oyabu, Takako; Horie, Masanori; Kambara, Tatsunori; Izumi, Hiroto; Kuroda, Etsushi; Creutzenberg, Otto; Bellmann, Bernd; Pohlmann, Gerhard; Schuchardt, Sven; Hansen, Tanja; Ernst, Heinrich

    2013-10-01

    The pulmonary effects of a finished toner were evaluated in intratracheal instillation and inhalation studies, using toners with external additives (titanium dioxide nanoparticles and amorphous silica nanoparticles). Rats received an intratracheal dose of 1 mg or 2 mg of toner and were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months. The toner induced pulmonary inflammation, as evidenced by a transient neutrophil response in the low-dose groups and persistent neutrophil infiltration in the high-dose groups. There were increased concentrations of heme oxygenase-1 (HO-1) as a marker of oxidative stress in the bronchoalveolar lavage fluid (BALF) and the lung. In a 90-day inhalation study, rats were exposed to well-dispersed toner (mean of MMAD: 3.76 µm). The three mass concentrations of toner were 1, 4 and 16 mg/m(3) for 13 weeks, and the rats were sacrificed at 6 days and 91 days after the end of the exposure period. The low and medium concentrations did not induce neutrophil infiltration in the lung of statistical significance, but the high concentration did, and, in addition, upon histopathological examination not only showed findings of inflammation but also of fibrosis in the lung. Taken together, the results of our studies suggest that toners with external additives lead to pulmonary inflammation and fibrosis at lung burdens suggest beyond the overload. The changes observed in the pulmonary responses in this inhalation study indicate that the high concentration (16 mg/m(3)) is an LOAEL and that the medium concentration (4 mg/m(3)) is an NOAEL.

  7. Acute inhalation toxicity of carbonyl sulfide

    SciTech Connect

    Benson, J.M.; Hahn, F.F.; Barr, E.B.

    1995-12-01

    Carbonyl sulfide (COS), a colorless gas, is a side product of industrial procedures sure as coal hydrogenation and gasification. It is structurally related to and is a metabolite of carbon disulfide. COS is metabolized in the body by carbonic anhydrase to hydrogen sulfide (H{sub 2}S), which is thought to be responsible for COS toxicity. No threshold limit value for COS has been established. Results of these studies indicate COS (with an LC{sub 50} of 590 ppm) is slightly less acutely toxic than H{sub 2}S (LC{sub 50} of 440 ppm).

  8. Inhalation dosimetry modeling provides insights into regional respiratory tract toxicity of inhaled diacetyl.

    PubMed

    Cichocki, Joseph A; Morris, John B

    2016-11-13

    Vapor dosimetry models provide a means of assessing the role of delivered dose in determining the regional airway response to inspired vapors. A validated hybrid computational fluid dynamics physiologically based pharmacokinetic model for inhaled diacetyl has been developed to describe inhaled diacetyl dosimetry in both the rat and human respiratory tracts. Comparison of the distribution of respiratory tract injury with dosimetry estimates provides strong evidence that regional delivered dose rather than regional airway tissue sensitivity to diacetyl-induced injury is the critical determinant of the regional respiratory tract response to this water soluble reactive vapor. In the rat, inhalation exposure to diacetyl causes much lesser injury in the distal bronchiolar airways compared to nose and large tracheobronchial airways. The degree of injury correlates very strongly to model based estimates of local airway diacetyl concentrations. According to the model, regional dosimetry patterns of diacetyl in the human differ greatly from those in the rat with much greater penetration of diacetyl to the bronchiolar airways in the lightly exercising mouth breathing human compared to the rat, providing evidence that rat inhalation toxicity studies underpredict the risk of bronchiolar injury in the human. For example, repeated exposure of the rat to 200ppm diacetyl results in bronchiolar injury; the estimated bronchiolar tissue concentration in rats exposed to 200ppm diacetyl would occur in lightly exercising mouth breathing humans exposed to 12ppm. Consideration of airway dosimetry patterns of inspired diacetyl is critical to the proper evaluation of rodent toxicity data and its relevance for predicting human risk.

  9. Cadmium inhalation and male reproductive toxicity

    SciTech Connect

    Ragan, H.A.; Mast, T.J. )

    1990-01-01

    Cadmium is a highly toxic element that is cumulative and has a long biological half-life in mammals. The severe toxicity of cadmium in man has been known for more than 100 years. Despite the knowledge that cadmium is toxic, only 20 human cases of poisoning via ingestion were recorded prior to 1941, whereas in the ensuing five-year period more than 680 cases of cadmium poisonings from accidental oral ingestion of this metal were documented. Some of the recorded effects of exposure to cadmium in laboratory animals include renal tubular damage, placental and testicular necrosis, structural and functional liver damage, osteomalacia, testicular tumors, teratogenic malformations, anemia, hypertension, pulmonary edema, chronic pulmonary emphysema, and induced deficiencies of iron, copper, and zinc. Some of these effects have also been observed in human after accidental exposures to cadmium oxide fumes and are characteristic of the syndrome described in Japan as Itai Itai disease in which ingestion of cadmium is the inciting chemical.134 references.

  10. Evaluation of the Tobacco Heating System 2.2 (THS2.2). Part 5: microRNA expression from a 90-day rat inhalation study indicates that exposure to THS2.2 aerosol causes reduced effects on lung tissue compared with cigarette smoke.

    PubMed

    Sewer, Alain; Kogel, Ulrike; Talikka, Marja; Wong, Ee Tsin; Martin, Florian; Xiang, Yang; Guedj, Emmanuel; Ivanov, Nikolai V; Hoeng, Julia; Peitsch, Manuel C

    2016-11-30

    Modified-risk tobacco products (MRTP) are designed to reduce the individual risk of tobacco-related disease as well as population harm compared to smoking cigarettes. Experimental proof of their benefit needs to be provided at multiple levels in research fields. Here, we examined microRNA (miRNA) levels in the lungs of rats exposed to a candidate modified-risk tobacco product, the Tobacco Heating System 2.2 (THS2.2) in a 90-day OECD TG-413 inhalation study. Our aim was to assess the miRNA response to THS2.2 aerosol compared with the response to combustible cigarettes (CC) smoke from the reference cigarette 3R4F. CC smoke exposure, but not THS2.2 aerosol exposure, caused global miRNA downregulation, which may be explained by the interference of CC smoke constituents with the miRNA processing machinery. Upregulation of specific miRNA species, such as miR-146a/b and miR-182, indicated that they are causal elements in the inflammatory response in CC-exposed lungs, but they were reduced after THS2.2 aerosol exposure. Transforming transcriptomic data into protein activity based on corresponding downstream gene expression, we identified potential mechanisms for miR-146a/b and miR-182 that were activated by CC smoke but not by THS2.2 aerosol and possibly involved in the regulation of those miRNAs. The inclusion of miRNA profiling in systems toxicology approaches increases the mechanistic understanding of the complex exposure responses.

  11. Toxic inhalation fatalities of US construction workers, 1990 to 1999.

    PubMed

    Dorevitch, Samuel; Forst, Linda; Conroy, Lorraine; Levy, Paul

    2002-07-01

    Construction workers account for a disproportionately large number of occupational fatalities. A small percentage of these deaths is attributable to poisoning. Risk factors for such deaths using national data have not been reported previously. Construction poisoning fatalities from 1990 to 1999 in the Occupational Safety and Health Administration Integrated Management and Information System data set were analyzed. Risk and risk factors were determined using Bureau of Labor Statistics and census data. Eighty-seven poisoning deaths of construction workers are characterized, all attributable to toxic inhalation. Cellular and simple asphyxiants accounted for the largest numbers of fatalities. The majority of these deaths occurred in confined spaces. Water, sewer, and utility line workers are at increased risk for poisoning fatality. Toxic inhalation fatalities in the construction industry are preventable. Extending the Occupational Safety and Health Administration's confined space standard could save lives, particularly among water, sewer, and utility line industry workers.

  12. Changing the dose metric for inhalation toxicity studies: short-term study in rats with engineered aerosolized amorphous silica nanoparticles.

    PubMed

    Sayes, Christie M; Reed, Kenneth L; Glover, Kyle P; Swain, Keith A; Ostraat, Michele L; Donner, E Maria; Warheit, David B

    2010-03-01

    Inhalation toxicity and exposure assessment studies for nonfibrous particulates have traditionally been conducted using particle mass measurements as the preferred dose metric (i.e., mg or microg/m(3)). However, currently there is a debate regarding the appropriate dose metric for nanoparticle exposure assessment studies in the workplace. The objectives of this study were to characterize aerosol exposures and toxicity in rats of freshly generated amorphous silica (AS) nanoparticles using particle number dose metrics (3.7 x 10(7) or 1.8 x 10(8) particles/cm(3)) for 1- or 3-day exposures. In addition, the role of particle size (d(50) = 37 or 83 nm) on pulmonary toxicity and genotoxicity endpoints was assessed at several postexposure time points. A nanoparticle reactor capable of producing, de novo synthesized, aerosolized amorphous silica nanoparticles for inhalation toxicity studies was developed for this study. SiO(2) aerosol nanoparticle synthesis occurred via thermal decomposition of tetraethylorthosilicate (TEOS). The reactor was designed to produce aerosolized nanoparticles at two different particle size ranges, namely d(50) = approximately 30 nm and d(50) = approximately 80 nm; at particle concentrations ranging from 10(7) to 10(8) particles/cm(3). AS particle aerosol concentrations were consistently generated by the reactor. One- or 3-day aerosol exposures produced no significant pulmonary inflammatory, genotoxic, or adverse lung histopathological effects in rats exposed to very high particle numbers corresponding to a range of mass concentrations (1.8 or 86 mg/m(3)). Although the present study was a short-term effort, the methodology described herein can be utilized for longer-term inhalation toxicity studies in rats such as 28-day or 90-day studies. The expansion of the concept to subchronic studies is practical, due, in part, to the consistency of the nanoparticle generation method.

  13. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...—adrenals, parathyroid, thyroid. (D) Respiratory system—trachea, lungs, pharynx, larynx, nose. (E..., but not be limited to, evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects, including...

  14. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...—adrenals, parathyroid, thyroid. (D) Respiratory system—trachea, lungs, pharynx, larynx, nose. (E..., but not be limited to, evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects, including...

  15. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...—adrenals, parathyroid, thyroid. (D) Respiratory system—trachea, lungs, pharynx, larynx, nose. (E..., but not be limited to, evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects, including...

  16. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...—adrenals, parathyroid, thyroid. (D) Respiratory system—trachea, lungs, pharynx, larynx, nose. (E..., but not be limited to, evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects, including...

  17. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...—adrenals, parathyroid, thyroid. (D) Respiratory system—trachea, lungs, pharynx, larynx, nose. (E..., but not be limited to, evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects, including...

  18. MODELING APPROACHES FOR ESTIMATING THE DOSIMETRY OF INHALED TOXICANTS IN CHILDREN

    EPA Science Inventory

    Risk assessment of inhaled toxicants has typically focused upon adults, with modeling used to extrapolate dosimetry and risks from laboratory animals to humans. However, behavioral factors such as time spent playing outdoors can lead to more exposure to inhaled toxicants in chil...

  19. Application of short-term inhalation studies to assess the inhalation toxicity of nanomaterials

    PubMed Central

    2014-01-01

    Background A standard short-term inhalation study (STIS) was applied for hazard assessment of 13 metal oxide nanomaterials and micron-scale zinc oxide. Methods Rats were exposed to test material aerosols (ranging from 0.5 to 50 mg/m3) for five consecutive days with 14- or 21-day post-exposure observation. Bronchoalveolar lavage fluid (BALF) and histopathological sections of the entire respiratory tract were examined. Pulmonary deposition and clearance and test material translocation into extra-pulmonary organs were assessed. Results Inhaled nanomaterials were found in the lung, in alveolar macrophages, and in the draining lymph nodes. Polyacrylate-coated silica was also found in the spleen, and both zinc oxides elicited olfactory epithelium necrosis. None of the other nanomaterials was recorded in extra-pulmonary organs. Eight nanomaterials did not elicit pulmonary effects, and their no observed adverse effect concentrations (NOAECs) were at least 10 mg/m3. Five materials (coated nano-TiO2, both ZnO, both CeO2) evoked concentration-dependent transient pulmonary inflammation. Most effects were at least partially reversible during the post-exposure period. Based on the NOAECs that were derived from quantitative parameters, with BALF polymorphonuclear (PMN) neutrophil counts and total protein concentration being most sensitive, or from the severity of histopathological findings, the materials were ranked by increasing toxic potency into 3 grades: lower toxic potency: BaSO4; SiO2.acrylate (by local NOAEC); SiO2.PEG; SiO2.phosphate; SiO2.amino; nano-ZrO2; ZrO2.TODA; ZrO2.acrylate; medium toxic potency: SiO2.naked; higher toxic potency: coated nano-TiO2; nano-CeO2; Al-doped nano-CeO2; micron-scale ZnO; coated nano-ZnO (and SiO2.acrylate by systemic no observed effect concentration (NOEC)). Conclusion The STIS revealed the type of effects of 13 nanomaterials, and micron-scale ZnO, information on their toxic potency, and the location and reversibility of effects

  20. Trichloromelamine 14-Day Range Finding and 90-Day Subchronic Studies in Rats. 3 August 1988 - 17 January 1989. Phase 2

    DTIC Science & Technology

    1992-11-13

    COSATI CODES 10. SUBJECT TERMS (Continue on reverne if necessary and identify by block number) FIELD GROUP SUB-GROUP Trichloroemelamine, toxicity , 14-Day...90-Day 19, ABSTRACT (Conamnue on revers if necessary and identify by block number) The subchronic study examined the toxicity of the food service...observed adverse effect level in the 90-day study was 30 mg/kg/day. Trichloromelamine should be considered moderately toxic when ingested acutely

  1. Inhalation toxicity of lithium combustion aerosols in rats

    SciTech Connect

    Greenspan, B.J.; Allen, M.D.; Rebar, A.H.

    1986-01-01

    Studies of the acute inhalation toxicity of lithium combustion aerosols were undertaken to aid in evaluating the health hazards associated with the proposed use of lithium metal in fusion reactors. Male and female F344/Lov rats, 9-12 wk of age, were exposed once for 4 h to concentrations of 2600, 2300, 1400, or 620 mg/m/sup 3/ of aerosol (MMAD = 0.69 ..mu..m, sigma/sub g/ = 1.45) that was approximately 80% lithium carbonate and 20% lithium hydroxide to determine the acute toxic effects. Fourteen-day LC50 values (with 95% confidence limits) of 1700 (1300-2000) mg/m/sup 3/ for the male rats and 2000 (1700-2400) mg/m/sup 3/ for the female rate were calculated. Clinical signs of anorexia, dehydration, respiratory difficulty, and perioral and perinasal encrustation were observed. Body weights were decreased the first day after exposure in relation to the exposure concentration. In animals observed for an additional 2 wk, body weights, organ weights, and clinical signs began to return to pre-exposure values. Histopathologic examination of the respiratory tracts from the animals revealed ulcerative or necrotic laryngitis, focal to segmental ulcerative rhinitis often accompanied by areas of squamous metaplasia, and, in some cases, a suppurative bronchopneumonia or aspiration pneumonia, probably secondary to the laryngeal lesions. The results of these studies indicate the moderate acute toxicity of lithium carbonate aerosols and will aid in the risk analysis of accidental releases of lithium combustion aerosols.

  2. Assessment of chronic inhalation non-cancer toxicity for diethylamine

    PubMed Central

    Grant, Roberta L.; Taiwo, Samuel O.; McCant, Darrell

    2015-01-01

    Abstract A non-cancer inhalation chronic toxicity assessment for diethylamine (DEA, CAS number 109-89-7) was conducted by the Texas Commission on Environmental Quality. A chronic Reference Value (ReV) was determined based on a high-quality study conducted in mice and rats by the National Toxicology Program. Chronic inhalation ReVs are health-based exposure concentrations used in assessing health risks of long-term (i.e. lifetime) chemical exposure. DEA is used industrially as an organic intermediate to produce corrosion inhibitors, and is widely used in rubber, pharmaceuticals, resins, pesticides, insect repellants, dye processing and as a polymerization inhibitor. Although systemic effects have been noted at higher concentrations, DEA acts primarily as a respiratory irritant with effects occurring in the upper respiratory tract. Rats were exposed to 0, 31, 62.5 and 125 ppm DEA and mice to 0, 16, 31 and 62.5 ppm DEA for 6 h/day, 5 days/week for 105 weeks. Mice were slightly more sensitive than rats. The critical effect identified in mice was hyperostosis in the turbinates although DEA caused a number of other non-neoplatic lesions. Dose–response data were suitable to benchmark concentration (BMC) modeling. The human equivalent point of departure (PODHEC) was calculated from the 95% lower limit of the BMC(10) using default duration and animal-to-human dosimetric adjustments. Total uncertainty factors of 90 were applied to the PODHEC to account for variation in sensitivity within the human population, toxicodynamic differences between mice and humans, and database uncertainty. The chronic ReV for DEA is 11 ppb (33 µg/m3). PMID:26671196

  3. Inhalants

    MedlinePlus

    ... place a chemical- soaked rag in their mouth. Abusers may also inhale fumes from a balloon or ... by inhalants usually lasts just a few minutes, abusers often try to prolong it by continuing to ...

  4. Inhalants

    MedlinePlus

    ... Drug Facts Chat Day: Inhalants Drug Facts Chat Day: Inhalants Print Can you get high off of ... Cool Order Free Materials National Drugs & Alcohol Chat Day Newsletter Sign up to receive National Drug & Alcohol ...

  5. Photochemical Reaction Altered Cardiac Toxicity of Diesel Exhaust Inhalation

    EPA Science Inventory

    Rationale: Epidemiological studies have indicated an association between urban air pollution exposure and cardiovascular morbidity and mortality. The present study was designed to evaluate the cardiac effects of inhaled diesel exhaust and compared with photochemically altered d...

  6. Inhalation exposure and risk from mobile source air toxics in future years.

    PubMed

    Cook, Richard; Strum, Madeleine; Touma, Jawad S; Palma, Ted; Thurman, James; Ensley, Darrell; Smith, Roy

    2007-01-01

    Modeling of inhalation exposure and risks resulting from exposure to mobile source air toxics can be used to evaluate impacts of reductions from control programs on overall risk, as well as changes in relative contributions of different source sectors to risk, changes in contributions of different pollutants to overall risk, and changes in geographic distributions of risk. Such analysis is useful in setting regulatory priorities, and informing the decision-making process. In this paper, we have conducted national-scale air quality, exposure, and risk modeling for the US in the years 2015, 2020, and 2030, using similar tools and methods as the 1999 National-Scale Air Toxics Assessment. Our results suggest that US Environmental Protection Agency emission control programs will substantially reduce average inhalation cancer risks and potential noncancer health risks from exposure to mobile source air toxics. However, cancer risk and noncancer hazard due to inhalation of air toxics will continue to be a public health concern.

  7. Safety assessment of meat from transgenic cattle by 90-day feeding study in rats.

    PubMed

    Liu, Shan; Li, Chen-Xi; Feng, Xiao-Lian; Wang, Hui-Ling; Liu, Hai-Bo; Zhi, Yuan; Geng, Gui-Ying; Zhao, Jie; Xu, Hai-Bin

    2013-07-01

    The study was carried out to evaluate the subchronic toxicity of meat derived from human lactoferrin gene-modified cattle in male and female Wistar rats. Rats were fed 5% or 10% transgenic meat diet, 5% or 10% conventional meat diet, or AIN93G diet for 90 days. During the study, body weight and food consumption were weighed weekly and clinical observations were conducted daily. At the end of the study, urinary examination, hematology and blood biochemistry examination, macroscopic and microscopic examinations were performed. There were no biologically significant differences in these factors between the rat groups fed transgenic meat diet and conventional meat diet. Therefore, the present 90-day rodent feeding study suggests that meat derived from the transgenic cattle is equivalent to meat from conventional cattle in use as dietary supplements.

  8. An interesting case of characteristic methanol toxicity through inhalational exposure

    PubMed Central

    Kumar, Pratyush; Gogia, Atul; Kakar, Atul; Miglani, Pratyush

    2015-01-01

    Methanol poisoning is rare but carries high risk of morbidity and mortality. Most of the cases witnessed in emergency are due to consumption of adulterated alcohol. Here we are reporting a very rare case of methanol poisoning through inhalational exposure leading to putamen necrosis and decreased visual acuity. He had dyselectrolytemia and metabolic acidosis which was successfully managed with early intervention. Its importance lies in the fact that inhalational methanol poisoning is an entity which if picked up early can prevent long-term neurological sequelae. PMID:26285665

  9. U. S. Environmental Protection Agency's inhalation RFD methodology: Risk assessment for air toxics

    SciTech Connect

    Jarabek, A.M.; Menache, M.G.; Overton, J.H.; Dourson, M.L.; Miller, F.J.

    1989-01-01

    The U.S. Environmental Protection Agency (U.S. EPA) has advocated the establishment of general and scientific guidelines for the evaluation of toxicological data and their use in deriving benchmark values to protect exposed populations from adverse health effects. The Agency's reference dose (RfD) methodology for deriving benchmark values for noncancer toxicity originally addressed risk assessment of oral exposures. The paper presents a brief background on the development of the inhalation reference dose (RFDi) methodology, including concepts and issues related to addressing the dynamics of the respiratory system as the portal of entry. Different dosimetric adjustments are described that were incorporated into the methodology to account for the nature of the inhaled agent (particle or gas) and the site of the observed toxic effects (respiratory or extrarespiratory). Impacts of these adjustments on the extrapolation of toxicity data of inhaled agents for human health risk assessment and future research directions are also discussed.

  10. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... where in the respiratory tract such particles may be deposited. Concentration is expressed as weight of... of being inhaled and deposited anywhere within the respiratory tract . LC 50 (median lethal... to initiating the study, animals must be monitored for known viral and bacterial...

  11. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... where in the respiratory tract such particles may be deposited. Concentration is expressed as weight of... of being inhaled and deposited anywhere within the respiratory tract . LC 50 (median lethal... to initiating the study, animals must be monitored for known viral and bacterial...

  12. Toxicological assessment of kretek cigarettes Part 5: mechanistic investigations, inhalation toxicity.

    PubMed

    Roemer, E; Dempsey, R; Van Overveld, F J; Berges, A; Pype, J; Weiler, H; Vanscheeuwijck, P; Schorp, M K

    2014-12-01

    The biological effects of mainstream smoke (MS) from Indonesian-blended cigarettes with and without added cloves, cloves extracted with hot ethanol, and extracted cloves replenished with eugenol or clove oil were assessed in a 90-day inhalation study in rats. A separate 35-day inhalation study in rats was performed with MS from American-blended cigarettes with 0%, 2.5%, 5% or 10% added eugenol. Effects commonly seen in inhalation studies with MS were observed. These included histopathological changes indicative of irritation in the entire respiratory tract and inflammatory responses in the lung. Adding cloves to American- or Indonesian-blended cigarettes reduced the inflammatory response in the lung but with no difference between the two blend types. When the clove oil was extracted (∼ 75% reduction of eugenol achieved) from cloves, the inflammatory response in the lung was still reduced similarly to whole cloves but the severity of histopathological changes in the upper respiratory tract was less reduced. Add back of clove oil or pure eugenol reduced this response to a level similar to what was seen with whole cloves. When eugenol was added to American-blended cigarettes, similar findings of reduced lung inflammation and severity of histopathological changes in respiratory the tract was confirmed. These studies demonstrate a clear effect of cloves, and in particular eugenol, in explaining these findings.

  13. Inhalants

    MedlinePlus

    ... Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription Drugs & Cold ... Notes Articles Adolescent Cigarette, Alcohol Use Declines as Marijuana Use Rises ( February 2013 ) Program Helps Troubled Boys ...

  14. Toxicity of inhaled plutonium dioxide in beagle dogs

    SciTech Connect

    Muggenburg, M.A.; Guilmette, R.A.; Mewhinney, J.A.

    1996-03-01

    This study was conducted to determine the biological effects of inhaled {sup 238}PuO{sub 2} over the life spans of 144 beagle dogs. The dogs inhaled one of two sizes of monodisperse aerosols of {sup 238}PuO{sub 2} to achieve graded levels of initial lung burden (ILB). The aerosols also contained {sup 169}Yb to provide a {gamma}-ray-emitting label for the {sup 238}Pu inhaled by each dog. Excreta were collected periodically over each dog`s life span to estimate plutonium excretion; at death, the tissues were analyzed radiochemically for plutonium activity. The tissue content and the amount of plutonium excreted were used to estimate the ILB. These data for each dog were used in a dosimetry model to estimate the ILB. These data for each dog were used in a dosimetry model to estimate tissue doses. The lung, skeleton and liver received the highest {alpha}-particle doses, ranging from 0.16-68 Gy for the liver. At death, all dogs were necropsied, and all organs and lesions were sampled and examined by histopathology. Findings of non-neoplastic changes included neutropenia and lymphopenia that developed in a dose-related fashion soon after inhalation exposure. These effects persisted for up to 5 years in some animals, but no other health effects could be related to the blood changes observed. Radiation pneumonitis was observed among the dogs with the highest ILBs. Deaths from radiation pneumonitis occurred from 1.5 to 5.4 years after exposure. Tumors of the lung, skeleton and liver occurred beginning at about 3 years after exposure. These findings in dogs suggest that similar dose-related biological effects could be expected in humans accidentally exposed to {sup 238}PuO{sub 2}. 89 refs., 10 figs., 11 tab.

  15. Baroreflex Sensitivity Decreases During 90-Day Bed Rest

    NASA Technical Reports Server (NTRS)

    Stenger, M. B.; Arzeno, N. M.; Platts, S. H.

    2008-01-01

    Baroreflex sensitivity (BRS) decreases during spaceflight and simulated spaceflight (head down bed rest [BR]). However, previous studies have only examined BRS in response to a limited blood pressure (BP) range or to a single sudden change in BP. PURPOSE: The purpose of this study was to examine BRS during 90 days of 6deg head-down tilt BR over a broad range of BP perturbations. METHODS: Nineteen normal volunteers (12M, 7F) were tested one day before BR, and then near BR days 30, 60 and 90. BP was pharmacologically altered by continuous infusions of phenylephrine (PE) and sodium nitroprusside (SNP). Electrocardiogram and continuous BP were collected during 10 min of normal saline (NS), followed by increasing concentrations of PE (10 min each of 0.4, 0.8 and 1.6 micro-g/kg/min). After a 20 min break, NS was infused again for 10 min, followed by increasing concentrations of SNP (10 min each of 0.4, 0.8, 1.2 micro-g/kg/min). Baroreceptor sensitivity was measured as the slope of a sequence of 3 or more beats in which the systolic BP and following R-R interval (RR) both increased or decreased. Spectral heart rate variability (HRV) and mean RR were analyzed using data from only the NS infusions. Two-way repeated-measures analysis of variance was performed to examine the effects of BR and gender. RESULTS: RR decreased (p<0.001) from pre- BR across BR days. High frequency in normalized units, a measure of parasympathetic activity, decreased with BR (p=0.027) and was lower (p=0.046) in men (0.39+/-0.02, mean+/-SEM) than women (0.48+/-0.02). The spontaneous baroreflex slope, our measure of BRS, increased with PE and decreased with SNP across BR (p<0.001). The percentage decrease in BRS from pre- to post-BR appeared to be larger in women (43.6+/-7.0%) than in men (31.3+/-3.9%, p=0.06). CONCLUSION: Parasympathetic activity and baroreflex sensitivity decrease during 90 days of BR, and BRS tends to diminish more in women than in men.

  16. Assessment of Airborne Particles. Fundamentals, Applications, and Implications to Inhalation Toxicity.

    ERIC Educational Resources Information Center

    Mercer, Thomas T., Ed.; And Others

    Concern over chemical and radioactive particulate matter in industry and over rapidly increasing air pollution has stimulated research both on the properties of airborne particles and methods for assessing them and on their biological effects following inhalation. The Third Rochester International Conference on Environmental Toxicity was,…

  17. Overview of testing methods used in inhalation toxicity: from facts to artifacts.

    PubMed

    Pauluhn, Jürgen

    2003-04-11

    For smaller rodent species, homogenous in size and growth, small head or nose-only chambers are commonly used up to subchronic exposure durations, whereas larger whole-body exposure chambers are used for long-term exposures or exposure paradigms exceeding the normal working day. The advantages and disadvantages of each different technique have already been identified and published in detail. It is often believed best that whole-body inhalation chambers simulate potential human exposure to environmental chemicals or pesticides and this serves as a justification for preferring this mode of exposure. However, real-life exposure conditions of humans cannot be readily duplicated. A comparable mode of exposure may be employed rather than duplicating both the exposure regimens and atmospheres similar to those present in real-world settings. Especially in inhalation studies with complex mixtures, in which atmosphere generation is difficult to control, non-homogenous exposure atmospheres and artifacts are more likely to occur in larger whole-body chambers than in the smaller nose-only inhalation chambers. Inhalation studies with complex mixtures not only face all the challenges of traditional inhalation toxicity testing, but also they are frequently subject to artifacts not readily detected. Thus, a disproportionation of volatile and particulate constituents might occur in inhalation chambers depend on selected technical features, i.e., whether a dynamic or (quasi)static mode of exposure is chosen. Inappropriate timing of the sampling of biological specimens may lead to the underestimation of effects, especially in whole-body exposed animals.

  18. Lung Deposition Analyses of Inhaled Toxic Aerosols in Conventional and Less Harmful Cigarette Smoke: A Review

    PubMed Central

    Kleinstreuer, Clement; Feng, Yu

    2013-01-01

    Inhaled toxic aerosols of conventional cigarette smoke may impact not only the health of smokers, but also those exposed to second-stream smoke, especially children. Thus, less harmful cigarettes (LHCs), also called potential reduced exposure products (PREPs), or modified risk tobacco products (MRTP) have been designed by tobacco manufacturers to focus on the reduction of the concentration of carcinogenic components and toxicants in tobacco. However, some studies have pointed out that the new cigarette products may be actually more harmful than the conventional ones due to variations in puffing or post-puffing behavior, different physical and chemical characteristics of inhaled toxic aerosols, and longer exposure conditions. In order to understand the toxicological impact of tobacco smoke, it is essential for scientists, engineers and manufacturers to develop experiments, clinical investigations, and predictive numerical models for tracking the intake and deposition of toxicants of both LHCs and conventional cigarettes. Furthermore, to link inhaled toxicants to lung and other diseases, it is necessary to determine the physical mechanisms and parameters that have significant impacts on droplet/vapor transport and deposition. Complex mechanisms include droplet coagulation, hygroscopic growth, condensation and evaporation, vapor formation and changes in composition. Of interest are also different puffing behavior, smoke inlet conditions, subject geometries, and mass transfer of deposited material into systemic regions. This review article is intended to serve as an overview of contributions mainly published between 2009 and 2013, focusing on the potential health risks of toxicants in cigarette smoke, progress made in different approaches of impact analyses for inhaled toxic aerosols, as well as challenges and future directions. PMID:24065038

  19. Toxicological Considerations, Toxicity Assessment, and Risk Management of Inhaled Nanoparticles

    PubMed Central

    Bakand, Shahnaz; Hayes, Amanda

    2016-01-01

    Novel engineered nanoparticles (NPs), nanomaterial (NM) products and composites, are continually emerging worldwide. Many potential benefits are expected from their commercial applications; however, these benefits should always be balanced against risks. Potential toxic effects of NM exposure have been highlighted, but, as there is a lack of understanding about potential interactions of nanomaterials (NMs) with biological systems, these side effects are often ignored. NPs are able to translocate to the bloodstream, cross body membrane barriers effectively, and affect organs and tissues at cellular and molecular levels. NPs may pass the blood–brain barrier (BBB) and gain access to the brain. The interactions of NPs with biological milieu and resulted toxic effects are significantly associated with their small size distribution, large surface area to mass ratio (SA/MR), and surface characteristics. NMs are able to cross tissue and cell membranes, enter into cellular compartments, and cause cellular injury as well as toxicity. The extremely large SA/MR of NPs is also available to undergo reactions. An increased surface area of the identical chemical will increase surface reactivity, adsorption properties, and potential toxicity. This review explores biological pathways of NPs, their toxic potential, and underlying mechanisms responsible for such toxic effects. The necessity of toxicological risk assessment to human health should be emphasised as an integral part of NM design and manufacture. PMID:27314324

  20. Range Finding 14-Day and 90-Day Subchronic Feeding Studies with N,N-Dipropylcyclohexanecarboxamide in Rats. Phase 4.

    DTIC Science & Technology

    1986-12-01

    clinical chemistry values. Significant increases occurred in male rat liver organ-to-body weight ratios in all three dose levels at the 45 and 90 day necropsies during the 90-day feeding study. A no effect dose was not achieved during this study. Additional testing would be required to confirm a no effect dose level. It is concluded that a toxic hazard may exist from a prolonged significant oral exposure to N,N-Dopropylcyclohexanecarboxamide. It is recommended that further evaluation of this compound as a candidate insect repellent be discontinued due to the deleterious

  1. Cold blast furnace syndrome: a new source of toxic inhalation by nitrogen oxides

    PubMed Central

    Tague, I; Llewellin, P; Burton, K; Buchan, R; Yates, D

    2004-01-01

    Methods: Fourteen workers developed acute respiratory symptoms shortly after exposure to "air blast" from blast furnace tuyeres. These included chest tightness, dyspnoea, rigors, and diaphoresis. Chest radiographs showed pulmonary infiltrates, and lung function a restrictive abnormality. This report includes a description of clinical features of the affected workers and elucidation of the probable cause of the outbreak. Results: Clinical features and occupational hygiene measurements suggested the most likely cause was inhalation of nitrogen oxides at high pressure and temperature. While the task could not be eliminated, engineering controls were implemented to control the hazard. No further cases have occurred. Conclusions: "Cold blast furnace syndrome" represents a previously undescribed hazard of blast furnace work, probably due to inhalation of nitrogen oxides. It should be considered in the differential diagnosis of acute toxic inhalational injuries in blast furnace workers. PMID:15090669

  2. 40 CFR 798.4350 - Inhalation developmental toxicity study.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue... million (ppm). (6) “No-observed-effect level” is the maximum concentration in a test which produces no observed adverse effects. A no-observed-effect level is expressed in terms of weight or volume of...

  3. 40 CFR 798.4350 - Inhalation developmental toxicity study.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... should not come in direct contact with the test atmospheres. (9) Observation of animals. (i) A gross... Academy of Sciences. “Principles and Procedures for Evaluating the Toxicity of Household Substances.” A... Committee on Toxicology, National Research Council, National Academy of Sciences, Washington, DC (1977)....

  4. Acute and Subchronic Toxicity of Inhaled Toluene in Male ...

    EPA Pesticide Factsheets

    The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute and one subchronic, were conducted to seek effects of the VOC, toluene, in rats and to compare the effects between acute and subchronic exposures. Adult male Long-Evans rats were exposed to toluene vapor (n = 6 per group) at a concentration of 0 or l 019 ± 14 ppm for 6 h in the acute study and at 0 ± 0, 10 ± 1.4, 97 ± 7, or 995 ± 43 ppm for 6 h/d, 5 d/week for 13 weeksin the subchronic study. For the acute study, brains were dissected on ice within 30 min of the end of exposure, while for the subchronic study, brains were dissected 18 h after the last exposure. Frontal cortex, hippocampus, cerebellum, and striatum were assayed for a variety of oxidative stress (OS) parameters including total aconitase (TA), protein carbonyls, glutathione peroxidase (GPX), glutathione reductase (GRD), glutathione transferase (GST), y-­glutamylcysteine synthetase (GCS), superoxide dismutase (SOD), total antioxidants (TAS), NADPH quinone oxidoreductase- 1 (NQO1 ), and NADH ubiquinone reductase (UBIQ-RD) activities using commercially available kits. Following acute exposure, UBIQ-RD, GCS and GRD were increased significantly only in the cerebellum, while TAS was increased in frontal cortex. On the other

  5. Acute inhalation toxicity and sensory irritation of dimethylamine. [Rats, mice

    SciTech Connect

    Steinhagen, W.H.; Swenberg, J.A.; Barrow, C.S.

    1982-06-01

    The sensory irritation potential of dimethylamine (DMA) inhalation on male Fischer-344 rats and male Swiss-Webster mice was evaluated by measuring the reflex decrease in respiratory rate. In addition, the six hour LC/sub 50/ for rats exposed to dimetylamine was established. Groups of 3 or 4 rats and mice were exposed for 10 minutes to concentrations of DMA ranging from 49 to 1576 ppm during which time the respiratory rate was monitored and recorded. Sensory irritation concentration-response curves were obtained and RD/sub 50/ values (concentration which elicits a 50% decrease in respiratory rate) were determined to be 573 and 511 ppm for rats and mice, respectively. In another set of experiments seven groups of male rats were exposed to concentrations of DMA ranging from 600 to 6119 ppm for six hours. Mortality counts were made during and for 48 hours post exposure. The six hour LC/sub 50/ was determined to be 4540 ppm. Histopathologic examination of the respiratory tract revealed concentration related changes ranging from ulceration and necrosis to rhinitis, tracheitis, and emphysema. Overall, DMA was found to be less potent as a sensory irritant than other airborne irritants.

  6. Inhalation toxicity of 316L stainless steel powder in relation to bioaccessibility.

    PubMed

    Stockmann-Juvala, H; Hedberg, Y; Dhinsa, N K; Griffiths, D R; Brooks, P N; Zitting, A; Wallinder, I Odnevall; Santonen, T

    2013-11-01

    The Globally Harmonized System for Classification and Labelling of Chemicals (GHS) considers metallic alloys, such as nickel (Ni)-containing stainless steel (SS), as mixtures of substances, without considering that alloys behave differently compared to their constituent metals. This study presents an approach using metal release, explained by surface compositional data, for the prediction of inhalation toxicity of SS AISI 316L. The release of Ni into synthetic biological fluids is >1000-fold lower from the SS powder than from Ni metal, due to the chromium(III)-rich surface oxide of SS. Thus, it was hypothesized that the inhalation toxicity of SS is significantly lower than what could be predicted based on Ni metal content. A 28-day inhalation study with rats exposed to SS 316L powder (<4 µm, mass median aerodynamic diameter 2.5-3.0 µm) at concentrations up to 1.0 mg/L showed accumulation of metal particles in the lung lobes, but no signs of inflammation, although Ni metal caused lung toxicity in a similar published study at significantly lower concentrations. It was concluded that the bioaccessible (released) fraction, rather than the elemental nominal composition, predicts the toxicity of SS powder. The study provides a basis for an approach for future validation, standardization and risk assessment of metal alloys.

  7. The toxicity of inhaled particles of sup 238 PuO sub 2 in dogs

    SciTech Connect

    Muggenburg, B.A.; Guilmette, R.A.; Griffith, W.C. Jr.; Hahn, F.F.; Boecker, B.B. . Inhalation Toxicology Research Inst.); Gillett, N.A. )

    1991-01-01

    This study was conducted to determine the toxicity of inhaled {sup 238}PuO{sub 2} in the dog. Inhalation was selected because it is the mostly likely route of human exposure in the event of an accidental airborne release. Of 166 dog in the study, 72 inhaled 1.5{mu}m and 72 inhaled 3.0 {mu}m activity median aerodynamic diameter particles of {sup 238}PuO{sub 2}. Another 24 dogs inhaled the aerosol vector without plutonium. The aerosol exposures resulted in initial pulmonary burdens ranging from 37 to 0.11 and 55.5 to 0.37 kBq of {sup 238}Pu/kg body mass, of 1.5 {mu}m and 3.0 {mu}, particles, respectively. The particles dissolved slowly resulting in translocation of the Pu to liver, bone and other sites. The dogs were observed for biological effects over their life span. Necropsies were performed at death, and tissues were examined microscopically. The principal late-occurring effects were tumors of the lung, skeleton, and liver. Risk factors estimated for these cancers were 2800 lung cancers/10{sup 4} Gy, 800 liver cancers/10{sup 4} Gy, and 6200 bone cancers/10{sup 4} Gy for dogs. The potential hazard from {sup 238}Pu to humans may include tumors of the lung, bone and liver because of the likelihood of similarity of the dose patterns for the two species. 10 refs., 1 fig., 3 tabs.

  8. Toxicity of Phosgene to White Mice by Inhalation

    DTIC Science & Technology

    1932-11-21

    Ph.G. Aooession ParI 1A u1 SW. S.-0 1 ..9.. TOXICITY OF PEOSGENE TO WHITE MICE BY INHkLATION. ABSTRU&T Objeots pe The object of this work was to...phongeno, where the chief ’"," ..’ -.: OAU4e Of death i0 puBL~Oniry sea, it is possible that the 48-hr.’, ,- d[eths are the4 beso index of the

  9. Lung inflammation caused by inhaled toxicants: a review

    PubMed Central

    Wong, John; Magun, Bruce E; Wood, Lisa J

    2016-01-01

    Exposure of the lungs to airborne toxicants from different sources in the environment may lead to acute and chronic pulmonary or even systemic inflammation. Cigarette smoke is the leading cause of chronic obstructive pulmonary disease, although wood smoke in urban areas of underdeveloped countries is now recognized as a leading cause of respiratory disease. Mycotoxins from fungal spores pose an occupational risk for respiratory illness and also present a health hazard to those living in damp buildings. Microscopic airborne particulates of asbestos and silica (from building materials) and those of heavy metals (from paint) are additional sources of indoor air pollution that contributes to respiratory illness and is known to cause respiratory illness in experimental animals. Ricin in aerosolized form is a potential bioweapon that is extremely toxic yet relatively easy to produce. Although the aforementioned agents belong to different classes of toxic chemicals, their pathogenicity is similar. They induce the recruitment and activation of macrophages, activation of mitogen-activated protein kinases, inhibition of protein synthesis, and production of interleukin-1 beta. Targeting either macrophages (using nanoparticles) or the production of interleukin-1 beta (using inhibitors against protein kinases, NOD-like receptor protein-3, or P2X7) may potentially be employed to treat these types of lung inflammation without affecting the natural immune response to bacterial infections. PMID:27382275

  10. The toxicity of continuous long-term low-dose formaldehyde inhalation in mice.

    PubMed

    Cheng, Jiaying; Zhang, Long; Tang, Yufu; Li, Zhenhai

    2016-12-01

    Although the toxicity of high-dose formaldehyde (FA) inhalation has been extensively analyzed in animals, the effect of continuous long-term exposure to low-dose FA has not been well documented. This study aims to evaluate the toxicity of continuous long-term low-dose FA inhalation in mice. Forty-eight Kunming male mice were equally randomized to three groups according to the dose of FA inhalation exposure: a control (0 mg/m(3)) group, a low-dose (0.08 mg/m(3)) group and a high-dose (0.8 mg/m(3)) group. The mice have been selected to expose to FA for different consecutive days at 24 h/day. The learning and memory functions, pathological changes in the lung and liver, and the percentage of CD4 (+) T and CD8 (+) T cells were observed and analyzed. It was found that continuous long-term inhalation of FA at relatively low doses could impair the learning and memory functions and induce pathological changes in the lung and liver, but did not seem to significantly affect the number of immune (CD4 (+) T and CD8 (+) T) cells.

  11. Toxicity of lunar dust assessed in inhalation-exposed rats

    PubMed Central

    Lam, Chiu-wing; Scully, Robert R.; Zhang, Ye; Renne, Roger A.; Hunter, Robert L.; McCluskey, Richard A.; Chen, Bean T.; Castranova, Vincent; Driscoll, Kevin E.; Gardner, Donald E.; McClellan, Roger O.; Cooper, Bonnie L.; McKay, David S.; Marshall, Linda; James, John T.

    2015-01-01

    Humans will again set foot on the moon. The moon is covered by a layer of fine dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m3 of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only exposure chambers were generated from a jet-mill ground preparation of a lunar soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13 weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of toxicity assessed in bronchoalveolar fluids showed concentration-dependent changes; biomarkers that showed treatment effects were total cell and neutrophil counts, total protein concentrations and cellular enzymes (lactate dehydrogenase, glutamyl transferase and aspartate transaminase). No statistically significant differences in these biomarkers were detected between rats exposed to air and those exposed to the two low concentrations of lunar dust. Dose-dependent histopathology, including inflammation, septal thickening, fibrosis and granulomas, in the lung was observed at the two higher exposure concentrations. No lesions were detected in rats exposed to ≤6.8 mg/m3. This 4-week exposure study in rats showed that 6.8 mg/m3 was the highest no-observable-adverse-effect level (NOAEL). These results will be useful for assessing the health risk to humans of exposure to lunar dust, establishing human exposure limits and guiding the design of dust mitigation systems in lunar landers or habitats. PMID:24102467

  12. Toxicity of lunar dust assessed in inhalation-exposed rats.

    PubMed

    Lam, Chiu-wing; Scully, Robert R; Zhang, Ye; Renne, Roger A; Hunter, Robert L; McCluskey, Richard A; Chen, Bean T; Castranova, Vincent; Driscoll, Kevin E; Gardner, Donald E; McClellan, Roger O; Cooper, Bonnie L; McKay, David S; Marshall, Linda; James, John T

    2013-10-01

    Humans will again set foot on the moon. The moon is covered by a layer of fine dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m(3) of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only exposure chambers were generated from a jet-mill ground preparation of a lunar soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13 weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of toxicity assessed in bronchoalveolar fluids showed concentration-dependent changes; biomarkers that showed treatment effects were total cell and neutrophil counts, total protein concentrations and cellular enzymes (lactate dehydrogenase, glutamyl transferase and aspartate transaminase). No statistically significant differences in these biomarkers were detected between rats exposed to air and those exposed to the two low concentrations of lunar dust. Dose-dependent histopathology, including inflammation, septal thickening, fibrosis and granulomas, in the lung was observed at the two higher exposure concentrations. No lesions were detected in rats exposed to ≤6.8 mg/m(3). This 4-week exposure study in rats showed that 6.8 mg/m(3) was the highest no-observable-adverse-effect level (NOAEL). These results will be useful for assessing the health risk to humans of exposure to lunar dust, establishing human exposure limits and guiding the design of dust mitigation systems in lunar landers or habitats.

  13. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Replacement housing payment for 90-day occupants... Payments § 24.402 Replacement housing payment for 90-day occupants. (a) Eligibility. A tenant or owner... occupied the displacement dwelling for at least 90 days immediately prior to the initiation of...

  14. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Replacement housing payment for 90-day occupants... Payments § 24.402 Replacement housing payment for 90-day occupants. (a) Eligibility. A tenant or owner... occupied the displacement dwelling for at least 90 days immediately prior to the initiation of...

  15. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Replacement housing payment for 90-day occupants... Payments § 24.402 Replacement housing payment for 90-day occupants. (a) Eligibility. A tenant or owner... occupied the displacement dwelling for at least 90 days immediately prior to the initiation of...

  16. 29 CFR 2590.715-2708 - Prohibition on waiting periods that exceed 90 days.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Prohibition on waiting periods that exceed 90 days. 2590... PLANS Other Requirements § 2590.715-2708 Prohibition on waiting periods that exceed 90 days. (a) General... not apply any waiting period that exceeds 90 days, in accordance with the rules of this section....

  17. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Replacement housing payment for 90-day mobile home... Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a mobile... 90 days immediately prior to the initiation of negotiations; (b) The person meets the other...

  18. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false Replacement housing payment for 90-day occupants... Payments § 24.402 Replacement housing payment for 90-day occupants. (a) Eligibility. A tenant or owner... occupied the displacement dwelling for at least 90 days immediately prior to the initiation of...

  19. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Replacement housing payment for 90-day mobile home... Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a mobile... 90 days immediately prior to the initiation of negotiations; (b) The person meets the other...

  20. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Replacement housing payment for 90-day occupants... Payments § 24.402 Replacement housing payment for 90-day occupants. (a) Eligibility. A tenant or owner... occupied the displacement dwelling for at least 90 days immediately prior to the initiation of...

  1. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Replacement housing payment for 90-day mobile home... Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a mobile... 90 days immediately prior to the initiation of negotiations; (b) The person meets the other...

  2. MODULAR APPLICATION OF COMPUTATIONAL MODELS OF INHALED REACTIVE GAS DOSIMETRY FOR RISK ASSESSMENT OF RESPIRATORY TRACT TOXICITY: CHLORINE

    EPA Science Inventory

    Inhaled reactive gases typically cause respiratory tract toxicity with a prominent proximal to distal lesion pattern. This pattern is largely driven by airflow and interspecies differences between rodents and humans result from factors such as airway architecture, ventilation ra...

  3. Inhalation Injuries

    MedlinePlus

    ... you can inhale that can cause acute internal injuries. Particles in the air from fires and toxic ... and lung diseases worse. Symptoms of acute inhalation injuries may include Coughing and phlegm A scratchy throat ...

  4. Aerosolized scopolamine protects against microinstillation inhalation toxicity to sarin in guinea pigs.

    PubMed

    Che, Magnus M; Chanda, Soma; Song, Jian; Doctor, Bhupendra P; Rezk, Peter E; Sabnekar, Praveena; Perkins, Michael W; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2011-07-01

    Sarin is a volatile nerve agent that has been used in the Tokyo subway attack. Inhalation is predicted to be the major route of exposure if sarin is used in war or terrorism. Currently available treatments are limited for effective postexposure protection against sarin under mass casualty scenario. Nasal drug delivery is a potential treatment option for mass casualty under field conditions. We evaluated the efficacy of endotracheal administration of muscarinic antagonist scopolamine, a secretion blocker which effectively crosses the blood-brain barrier for protection against sarin inhalation toxicity. Age and weight matched male Hartley guinea pigs were exposed to 677.4 mg/m³ or 846.5 mg/ m³ (1.2 × LCt₅₀) sarin by microinstillation inhalation exposure for 4 min. One minute later, the animals exposed to 846.5 mg/ m³ sarin were treated with endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24 h for efficacy evaluation. The results showed that treatment with scopolamine increased the survival rate from 20% to 100% observed in untreated sarin-exposed animals. Behavioral symptoms of nerve agent toxicity including, convulsions and muscular tremors were reduced in sarin-exposed animals treated with scopolamine. Sarin-induced body weight loss, decreased blood O₂ saturation and pulse rate were returned to basal levels in scopolamine-treated animals. Increased bronchoalveolar lavage (BAL) cell death due to sarin exposure was returned to normal levels after treatment with scopolamine. Taken together, these data indicate that postexposure treatment with aerosolized scopolamine prevents respiratory toxicity and protects against lethal inhalation exposure to sarin in guinea pigs.

  5. Comparative pulmonary toxicity of inhaled nickel nanoparticles; role of deposited dose and solubility.

    PubMed

    Kang, Gi Soo; Gillespie, Patricia A; Gunnison, Albert; Rengifo, Hernan; Koberstein, Jeffrey; Chen, Lung-Chi

    2011-02-01

    In this pilot study, we investigated which physicochemical properties of nickel hydroxide nanoparticles (nano-NH) were mainly responsible in inducing pulmonary toxicity. First, we studied the role of nickel ions solubilized from nano-NH by comparing the toxic effects of nano-NH to those of readily soluble nickel sulfate nanoparticles (nano-NS). Additionally, to test whether there was a non-specific stress response due to particle morphology, we compared the toxicity of nano-NH with that of carbon nanoparticles (nano-C) and titanium dioxide nanoparticles (nano-Ti), both of which had similar physical properties such as particle size and shape, to nano-NH. We exposed mice to each type of nanoparticles for 4?h via a whole-body inhalation system and examined oxidative stress and inflammatory responses in the lung. We also determined the lung burden and clearance of Ni following nano-NH and nano-NS exposures. The results showed that lung deposition of nano-NH was significantly greater than that of nano-NS and nano-NH appeared to have stronger inflammogenic potential than nano-NS even when lung Ni burden taken into consideration. This suggests that the toxicity of nano-NH is not driven solely by released Ni ions from deposited nano-NH particles. However, it is unlikely that the greater toxic potential of nano-NH is attributable to a generic stress response from any nanoparticle exposure, since nano-C and nano-Ti did not elicit toxic responses similar to those of nano-NH. These results indicate that the observed pulmonary toxicity by inhaled nano-NH were chemical-specific and deposited dose and solubility are key factors to understand toxicity induced by nano-NH.

  6. Toxicity and bio-accumulation of inhaled cerium oxide nanoparticles in CD1 mice.

    PubMed

    Aalapati, Srinivas; Ganapathy, Selvam; Manapuram, Saikumar; Anumolu, Goparaju; Prakya, Balakrishna Murthy

    2014-11-01

    Male CD1 mice were subjected to nose-inhalation exposure of CeO2 nanoparticles (NPs) for 0, 7, 14 or 28 days with 14 or 28 days of recovery time at an aerosol concentration of 2 mg/m(3). Markers of lung injury and pro-inflammatory cytokines (interleukin-1beta, tumour necrosis factor-alpha, interleukin-6 and macrophage inflammatory protein-2) in bronchoalveolar lavage fluid (BALF), oxidative stress in lungs, bio-accumulation, and histopathology of pulmonary and extrapulmonary tissues were assessed. BALF analysis revealed the induction of pulmonary inflammation, as evident by an increase in the influx of neutrophils with a significant secretion of pro-inflammatory cytokines that lead to generation of oxidative stress and cytotoxicity, as is evident by induction of lipid peroxidation, depletion of glutathione and increased BALF lactate dehydrogenase and protein. The histopathological examination revealed that these inhaled CeO2 NPs were located all over the pulmonary parenchyma, inducing a severe, chronic, active inflammatory response characterised by necrosis, proteinosis, fibrosis and well-formed discrete granulomas in the pulmonary tissue and tubular degeneration leading to coagulative necrosis in kidneys. Inductively coupled plasma optical emission spectrometer results showed a significant bio-accumulation of these particles in the pulmonary and extrapulmonary tissues, even after one month of post-inhalation exposure. Together, these findings suggest that inhalation exposure of CeO2 NPs can induce pulmonary and extrapulmonary toxicity.

  7. Relative toxicity of inhaled metal sulfate salts for pulmonary macrophages

    SciTech Connect

    Skornik, W.A.; Brain, J.D.

    1983-08-01

    The effects of metal sulfate aerosols on respiratory defense mechanisms in hamsters were studied. Pulmonary macrophage phagocytic rates were measured by determining the in vivo uptake of radioactive colloidal gold (/sup 198/Au) 1, 24, or 48 h after a single 4-h exposure. The concentrations of sulfate aerosols causing a 50% inhibition in pulmonary macrophage endocytosis (EC/sub 50/) were determined. When hamsters were exposed for 4 h to cupric sulfate (greater than or equal to 4.8 mg/m/sup 3/), zinc sulfate (greater than or equal to 3.1 mg/m/sup 3/), ferric sulfate (greater than or equal to 7.8 mg/m/sup 3/), or zinc ammonium sulfate (greater than or equal to 10.0 mg/m/sup 3/), macrophage endocytosis was significantly reduced 1 h after exposure compared with that in unexposed control animals. Although the response was variable, 24 h after exposures to the higher sulfate concentrations the percent of gold ingested by pulmonary macrophages remained depressed. By 48 h, the rate of macrophage endocytosis in hamsters had returned to normal control values except in hamsters exposed to 4.8 mg/m/sup 3/ cupric sulfate or 9.8 mg/m/sup 3/ ferric sulfate. These hamsters showed significant increases in phagocytosis. The EC/sub 50/ values in milligrams of sulfate per cubic meter for cupric sulfate, zinc sulfate, ferric sulfate, and zinc ammonium sulfate were 2.7, 4.5, 7.5, and 17.9, respectively. These results are negatively correlated with the ranking of sulfates using the criteria of relative irritant potency, as measured by increases in pulmonary flow resistance. Thus, rankings of related chemical structures are not absolute. Their relative toxicities vary depending on the end point selected.

  8. Relative toxicity of inhaled metal sulfate salts for pulmonary macrophages.

    PubMed

    Skornik, W A; Brain, J D

    1983-08-01

    The effects of metal sulfate aerosols on respiratory defense mechanisms in hamsters were studied. Pulmonary macrophage phagocytic rates were measured by determining the in vivo uptake of radioactive colloidal gold (198Au) 1, 24, or 48 h after a single 4-h exposure. The concentrations of sulfate aerosols causing a 50% inhibition in pulmonary macrophage endocytosis (EC50) were determined. When hamsters were exposed for 4 h to cupric sulfate (greater than or equal to 4.8 mg/m3), zinc sulfate (greater than or equal to 3.1 mg/m3), ferric sulfate (greater than or equal to 7.8 mg/m3), or zinc ammonium sulfate (greater than or equal to 10.0 mg/m3), macrophage endocytosis was significantly reduced 1 h after exposure compared with that in unexposed control animals. Although the response was variable, 24 h after exposures to the higher sulfate concentrations the percent of gold ingested by pulmonary macrophages remained depressed. By 48 h, the rate of macrophage endocytosis in hamsters had returned to normal control values except in hamsters exposed to 4.8 mg/m3 cupric sulfate or 9.8 mg/m3 ferric sulfate. These hamsters showed significant increases in phagocytosis. The EC50 values in milligrams of sulfate per cubic meter for cupric sulfate, zinc sulfate, ferric sulfate, and zinc ammonium sulfate were 2.7, 4.5, 7.5, and 17.9, respectively. These results are negatively correlated with the ranking of sulfates using the criteria of relative irritant potency, as measured by increases in pulmonary flow resistance. Thus, rankings of related chemical structures are not absolute. Their relative toxicities vary depending on the end point selected.

  9. Acute respiratory toxicity following inhalation exposure to soman in guinea pigs

    SciTech Connect

    Perkins, Michael W.; Pierre, Zdenka; Rezk, Peter; Sabnekar, Praveena; Sciuto, Alfred M.; Nambiar, Madhusoodana P.

    2010-06-01

    Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m{sup 3} concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m{sup 3} soman survived, while animals exposed to 841, and 1121 mg/m{sup 3} resulted in 38% and 13% survival, respectively. The microinstillation inhalation exposure LCt{sub 50} for soman determined by probit analysis was 827.2 mg/m{sup 3}. A majority of the animals that died at 1121 mg/m{sup 3} developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24 h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs.

  10. Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation

    PubMed Central

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro; Shimada, Manabu; Kubo, Masaru; Yamamoto, Kazuhiro; Kitajima, Shinichi; Kuroda, Etsushi; Kawaguchi, Kenji; Sasaki, Takeshi

    2016-01-01

    We conducted inhalation and intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m3) for four weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity. PMID:27490535

  11. Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

    NASA Astrophysics Data System (ADS)

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro; Shimada, Manabu; Kubo, Masaru; Yamamoto, Kazuhiro; Kitajima, Shinichi; Kuroda, Etsushi; Kawaguchi, Kenji; Sasaki, Takeshi

    2015-11-01

    We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO2) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO2 nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO2 nanoparticles (2, 10 mg/m3, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO2 nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO2 nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO2 nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO2 nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

  12. A 90-Day Feeding Study in Rats to Assess the Safety of Genetically Engineered Pork.

    PubMed

    Xiao, Gao-Jun; Jiang, Sheng-Wang; Qian, Li-Li; Cai, Chun-Bo; Wang, Qing-Qing; Ma, De-Zun; Li, Biao; Xie, Shan-Shan; Cui, Wen-Tao; Li, Kui

    2016-01-01

    Our laboratory recently produced genetically engineered (GE) Meishan pigs containing a ZFN-edited myostatin loss-of-function mutant. These GE pigs develop and grow as normal as wild type pigs but produce pork with greater lean yield and lower fat mass. To assess any potential subchronic toxicity risks of this GE pork, a 90-day feeding study was conducted in Sprague-Dawley rats. Rats were randomly divided into five groups, and fed for 90 days with basic diet and basic diets formulated with low dose and high dose pork prepared from wild type pigs and GE pigs, respectively. Animal behaviors and clinical signs were monitored twice daily, and body weight and food consumption were measured and recorded weekly. At days 45 and 90, blood tests (lipid panel, electrolytes, parameters related to liver and kidney functions, and complete blood counts) were performed. Additionally, gross pathology and histopathological analyses were performed for major organs in each group. Data analysis shows that there were no significant differences in growth rate, food consumption, and blood test parameters between rat groups fed with GE pork and wild type pork. Although differences in some liver function parameters (such as aspartate aminotransferase, total proteins, albumin, and alkaline phosphatase) and white blood cell counts (such as lymphocyte percentage and monocyte percentage) were observed between rats fed with high dose GE pork and basic diet, all test results in rats fed with GE pork are in the normal range. Additionally, there are no apparent lesions noted in all organs isolated from rats in all five feeding groups on days 45 and 90. Overall, our results clearly indicate that food consumption of GE pork produced by ZFN-edited myostatin loss-of-function mutant pigs did not have any long-term adverse effects on the health status in rats.

  13. A 90-Day Feeding Study in Rats to Assess the Safety of Genetically Engineered Pork

    PubMed Central

    Xiao, Gao-jun; Jiang, Sheng-Wang; Qian, Li-Li; Cai, Chun-Bo; Wang, Qing-qing; Ma, De-Zun; Li, Biao; Xie, Shan-shan; Cui, Wen-Tao; Li, Kui

    2016-01-01

    Our laboratory recently produced genetically engineered (GE) Meishan pigs containing a ZFN-edited myostatin loss-of-function mutant. These GE pigs develop and grow as normal as wild type pigs but produce pork with greater lean yield and lower fat mass. To assess any potential subchronic toxicity risks of this GE pork, a 90-day feeding study was conducted in Sprague-Dawley rats. Rats were randomly divided into five groups, and fed for 90 days with basic diet and basic diets formulated with low dose and high dose pork prepared from wild type pigs and GE pigs, respectively. Animal behaviors and clinical signs were monitored twice daily, and body weight and food consumption were measured and recorded weekly. At days 45 and 90, blood tests (lipid panel, electrolytes, parameters related to liver and kidney functions, and complete blood counts) were performed. Additionally, gross pathology and histopathological analyses were performed for major organs in each group. Data analysis shows that there were no significant differences in growth rate, food consumption, and blood test parameters between rat groups fed with GE pork and wild type pork. Although differences in some liver function parameters (such as aspartate aminotransferase, total proteins, albumin, and alkaline phosphatase) and white blood cell counts (such as lymphocyte percentage and monocyte percentage) were observed between rats fed with high dose GE pork and basic diet, all test results in rats fed with GE pork are in the normal range. Additionally, there are no apparent lesions noted in all organs isolated from rats in all five feeding groups on days 45 and 90. Overall, our results clearly indicate that food consumption of GE pork produced by ZFN-edited myostatin loss-of-function mutant pigs did not have any long-term adverse effects on the health status in rats. PMID:27812153

  14. Inhalation toxicity of 4-ethoxyaniline (p-phenetidine): critical analysis of results of subacute inhalation exposure studies in rats.

    PubMed

    Pauluhn, J; Mohr, U

    2001-11-01

    This article addresses results from a single 4-h and repeated 1- and 4-wk inhalation exposure studies in Wistar rats with vapor and/or aerosol atmospheres of 4-ethoxyaniline (p-phenetidine). Groups of 10 rats/sex were exposed nose-only to mean analytical concentrations of 11.1, 86.2, and 882.6 mg p-phenetidine/m(3) using an exposure regimen of 6 h/day, 5 days/wk for 4 wk. Concentrations were selected based on results from a pilot study in which rats were exposed under identical conditions on 5 consecutive days for 6 h/day to mean analytical concentrations of 38.2, 133.0, and 1247.6 mg/m(3). In repeated exposure studies, the focus of endpoints was on hematotoxicity. The LC50 was not determined, but no rats died following a single 4-h exposure to 5085 mg/m(3) as a mixture of vapor and aerosol. No mortality was observed either in the 1- or 4-wk studies. Rats exposed to 882.6 mg/m(3) and above evoked characteristic signs of toxicity that included cyanosis, with no apparent progression of findings during the exposure period. Animals exposed to 86.2 mg/m(3) and above exhibited a concentration-dependent, significant increase in blood methemoglobin and reticulocyte counts as well as a significant decrease in hemoglobin, hematocrit, and red blood cell counts. Spleen weights were significantly increased in groups exposed to 133.0 mg/m(3) and above. Microscopic changes demonstrated an increased hematopoiesis (bone marrow smears) and splenic hemosiderosis at 86.2 and 882.6 mg/m(3) and a hepatic hemosiderosis only at 882.6 mg/m(3). These data suggest that the toxicity of p-phenetidine is similar to that of its structural analog aniline. Based on the erythrocytotoxicity occurring at 86.2 mg/m(3) and above, including the apparent reactive changes in bone marrow (increased erythropoiesis) and spleen (increased erythroclasia), the no-observed-adverse-effect level (NOAEL) of the 4-wk study was 11.1 mg/m(3) air and that of the 1-wk study was 38.2 mg/m(3) air. This difference in

  15. Systematic Review and Meta-Analysis of Inhaled Toxicants from Waterpipe and Cigarette Smoking

    PubMed Central

    Carroll, Mary V.; Weiss, Patricia M.; Shihadeh, Alan L.; Shensa, Ariel; Farley, Steven T.; Fine, Michael J.; Eissenberg, Thomas; Nayak, Smita

    2016-01-01

    Objective Waterpipe tobacco smoking (WTS) is an emerging trend worldwide. To inform public health policy and educational programming, we systematically reviewed the biomedical literature to compute the inhaled smoke volume, nicotine, tar, and carbon monoxide (CO) associated with a single WTS session and a single cigarette. Methods We searched seven biomedical bibliographic databases for controlled laboratory or natural environment studies designed to mimic human tobacco consumption. Included studies quantified the mainstream smoke of a single cigarette and/or single WTS session for smoke volume, nicotine, tar, and/or CO. We conducted meta-analyses to calculate summary estimates for the inhalation of each unique substance for each mode of tobacco consumption. We assessed between-study heterogeneity using chi-squared and I-squared statistics. Results Sufficient data from 17 studies were available to derive pooled estimates for inhalation of each exposure via each smoking method. Two researchers working independently abstracted measurement of smoke volume in liters, and nicotine, tar, and CO in milligrams. All numbers included in meta-analyses matched precisely between the two researchers (100% agreement, Cohen's k=1.00). Whereas one WTS session was associated with 74.1 liters of smoke inhalation (95% confidence interval [CI] 38.2, 110.0), one cigarette was associated with 0.6 liters of smoke (95% CI 0.5, 0.7). One WTS session was also associated with higher levels of nicotine, tar, and CO. Conclusions One WTS session consistently exposed users to larger smoke volumes and higher levels of tobacco toxicants compared with one cigarette. These computed estimates may be valuable to emphasize in prevention programming. PMID:26843673

  16. 25 CFR 900.17 - Can the statutory 90-day period be extended?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Can the statutory 90-day period be extended? 900.17... ASSISTANCE ACT Review and Approval of Contract Proposals § 900.17 Can the statutory 90-day period be extended...-day deadline applies....

  17. 25 CFR 900.17 - Can the statutory 90-day period be extended?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Can the statutory 90-day period be extended? 900.17... ASSISTANCE ACT Review and Approval of Contract Proposals § 900.17 Can the statutory 90-day period be extended...-day deadline applies....

  18. 25 CFR 900.17 - Can the statutory 90-day period be extended?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 2 2014-04-01 2014-04-01 false Can the statutory 90-day period be extended? 900.17... ASSISTANCE ACT Review and Approval of Contract Proposals § 900.17 Can the statutory 90-day period be extended...-day deadline applies....

  19. 25 CFR 900.17 - Can the statutory 90-day period be extended?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Can the statutory 90-day period be extended? 900.17... ASSISTANCE ACT Review and Approval of Contract Proposals § 900.17 Can the statutory 90-day period be extended...-day deadline applies....

  20. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Replacement housing payment for 90-day mobile home... ASSISTANCE AND REAL PROPERTY ACQUISITION FOR FEDERAL AND FEDERALLY-ASSISTED PROGRAMS Mobile Homes § 24.503 Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a...

  1. Comparison of sarin and cyclosarin toxicity by subcutaneous, intravenous and inhalation exposure in Gottingen minipigs.

    PubMed

    Hulet, Stanley W; Sommerville, Douglas R; Miller, Dennis B; Scotto, Jacqueline A; Muse, William T; Burnett, David C

    2014-02-01

    Sexually mature male and female Gottingen minipigs were exposed to various concentrations of GB and GF vapor via whole-body inhalation exposures or to liquid GB or GF via intravenous or subcutaneous injections. Vapor inhalation exposures were for 10, 60 or 180 min. Maximum likelihood estimation was used to calculate the median effect levels for severe effects (ECT50 and ED50) and lethality (LCT50 and LD50). Ordinal regression was used to model the concentration × time profile of the agent toxicity. Contrary to that predicted by Haber's rule, LCT50 values increased as the duration of the exposures increased for both nerve agents. The toxic load exponents (n) were calculated to be 1.38 and 1.28 for GB and GF vapor exposures, respectively. LCT50 values for 10-, 60- and 180-min exposures to vapor GB in male minipigs were 73, 106 and 182 mg min/m(3), respectively. LCT50 values for 10-, 60 - and 180-min exposures to vapor GB in female minipigs were 87, 127 and 174 mg min/m(3), respectively. LCT50 values for 10-, 60- and 180-min exposures to vapor GF in male minipigs were 218, 287 and 403 mg min/m(3), respectively. LCT50 values for 10-, 60- and 180-min exposures in female minipigs were 183, 282 and 365 mg min/m(3), respectively. For GB vapor exposures, there was a tenuous gender difference which did not exist for vapor GF exposures. Surprisingly, GF was 2-3 times less potent than GB via the inhalation route of exposure regardless of exposure duration. Additionally GF was found to be less potent than GB by intravenous and subcutaneous routes.

  2. Improved dispersion method of multi-wall carbon nanotube for inhalation toxicity studies of experimental animals.

    PubMed

    Taquahashi, Yuhji; Ogawa, Yukio; Takagi, Atsuya; Tsuji, Masaki; Morita, Koichi; Kanno, Jun

    2013-01-01

    A multi-wall carbon nanotube (MWCNT) product Mitsui MWNT-7 is a mixture of dispersed single fibers and their agglomerates/aggregates. In rodents, installation of such mixture induces inflammatory lesions triggered predominantly by the aggregates/agglomerates at the level of terminal bronchiole of the lungs. In human, however, pulmonary toxicity induced by dispersed single fibers that reached the lung alveoli is most important to assess. Therefore, a method to generate aerosol predominantly consisting of dispersed single fibers without changing their length and width is needed for inhalation studies. Here, we report a method (designated as Taquann method) to effectively remove the aggregate/agglomerates and enrich the well-dispersed singler fibers in dry state without dispersant and without changing the length and width distribution of the single fibers. This method is base on two major concept; liquid-phase fine filtration and critical point drying to avoid re-aggregation by surface tension. MWNT-7 was suspended in Tert-butyl alcohol, freeze-and-thawed, filtered by a vibrating 25 µm mesh Metallic Sieve, snap-frozen by liquid nitrogen, and vacuum-sublimated (an alternative method to carbon dioxide critical point drying). A newly designed direct injection system generated well-dispersed aerosol in an inhalation chamber. The lung of mice exposed to the aerosol contained single fibers with a length distribution similar to the original and the Taquann-treated sample. Taquann method utilizes inexpensive materials and equipments mostly found in common biological laboratories, and prepares dry powder ready to make well-dispersed aerosol. This method and the chamber with direct injection system would facilitate the inhalation toxicity studies more relevant to human exposure.

  3. The First 90 Days of the New Middle School Principal in a Turnaround School: In-Depth Case Study of the Transition Period (First 90 Days)

    ERIC Educational Resources Information Center

    Baeza, Marco A.

    2010-01-01

    This study analyzed skills, strategies, and theories that new middle school principals used to be successful during their transition period (the first 90 days) in turnaround schools. Based on research on transitions, three research questions guided the study: 1. Do middle school principals in a turnaround school situation find the transition…

  4. Household insecticides: evaluation and assessment of inhalation toxicity: a workshop summary.

    PubMed

    Achmadi, U F; Pauluhn, J

    1998-03-01

    from that utilising a daily exposure. 3) In certain instances, inhalation testing of shorter duration, for example 2 or 4 weeks, may be appropriate if the inhalation toxicity of the basic formula has already been characterised or the major constituents contained in the formulation have been examined in extant studies. The duration of study should also depend on actual use and exposure pattern, the accumulation potential and the mode of action of the ingredients of concern. 4) Particularly for mosquito coil smokes, the possible physico-chemical interactions of particulates, potentially irritant water soluble or nonsoluble vapours and aerosol or vapours of the active ingredient(s) are virtually impossible to predict without appropriate inhalation testing. 5) Physiological measurements may be useful for the detection and quantification of the respiratory tract sensory irritation potency. Biochemical endpoints in lung lavage and conventional histopathology of the lungs and extrathoracic airways are considered to be important. 6) It has been agreed that the nose-only exposure technique provides the most cost-effective and controlled means to expose small laboratory animals to well defined atmospheres as long as the limitations of this technique are taken into account.

  5. Per- and polyfluoro toxicity (LC(50) inhalation) study in rat and mouse using QSAR modeling.

    PubMed

    Bhhatarai, Barun; Gramatica, Paola

    2010-03-15

    Fully or partially fluorinated compounds, known as per- and polyfluorinated chemicals are widely distributed in the environment and released because of their use in different household and industrial products. Few of these long chain per- and polyfluorinated chemicals are classified as emerging pollutants, and their environmental and toxicological effects are unveiled in the literature. This has diverted the production of long chain compounds, considered as more toxic, to short chains, but concerns regarding the toxicity of both types of per- and polyfluorinated chemicals are alarming. There are few experimental data available on the environmental behavior and toxicity of these compounds, and moreover, toxicity profiles are found to be different for the types of animals and species used. Quantitative structure-activity relationship (QSAR) is applied to a combination of short and long chain per- and polyfluorinated chemicals, for the first time, to model and predict the toxicity on two species of rodents, rat (Rattus) and mouse (Mus), by modeling inhalation (LC(50)) data. Multiple linear regression (MLR) models using the ordinary-least-squares (OLS) method, based on theoretical molecular descriptors selected by genetic algorithm (GA), were used for QSAR studies. Training and prediction sets were prepared a priori, and these sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the model was verified on a larger set of per- and polyfluorinated chemicals retrieved from different databases and journals. The descriptors involved, the similarities, and the differences observed between models pertaining to the toxicity related to the two species are discussed. Chemometric methods such as principal component analysis (PCA) and multidimensional scaling (MDS) were used to select most toxic compounds from those within the AD of both models, which will be subjected to experimental tests

  6. 4-Phenylcyclohexene: 2-week inhalation toxicity and neurotoxicity studies in Swiss-Webster mice.

    PubMed

    Beekman, M J; Maurissen, J P; Johnson, K A

    1996-09-01

    4-Phenylcyclohexene (4-PCH) is a by-product formed during the polymerization of styrene-butadiene latex used in carpet backing. Limited reports suggest that exposure to very low levels of 4-PCH or other emission products following new carpet installation may result in health complaints. Significantly, it has been claimed that Swiss-Webster mice held in neck restraints and exposed head-only to approximately 0.4 ppm 4-PCH for a few hours suffered severe toxicity including death. A 2-wk inhalation and neurotoxicity study was therefore conducted in Swiss-Webster mice using standard methods of toxicity testing. Groups of 40 mice were exposed to 0, 7, 18 or 71 ppm (near-saturated atmosphere) 4-PCH vapour, 6 hr/day for 9 consecutive days. Data were collected on a wide variety of clinical, neurological and histopathological parameters including extensive neurohistopathology. All animals survived the exposures, and there were no treatment-related effects. Because of the occurrence of spontaneous lesions in two high-dose group mice, 40 additional males were exposed to 0 ppm or a near-saturated atmosphere of 4-PCH under the same exposure regimen. No treatment-related lesions were observed in the follow-up study, confirming the conclusions of the original study. These findings, consistent with the reported lack of toxicity of inhaled 4-PCH in rats, do not suggest a direct, organic, association between low-level 4-PCH exposure and human complaints. Further, the results of this study suggest that positive findings in mice may have been due to methodological problems and not to exposure to 4-PCH.

  7. Propylene glycol monomethyl ether acetate (PGMEA) metabolism, disposition, and short-term vapor inhalation toxicity studies

    SciTech Connect

    Miller, R.R.; Hermann, E.A.; Young, J.T.; Calhoun, L.L.; Kastl, P.E.

    1984-09-30

    Male Fischer 344 rats were given a single po dose of approximately 8.7 mmol/kg of (1-14C)propylene glycol monomethyl ether acetate (PGMEA) or exposed to 3000 ppm (1-14C)PGMEA for 6 hr. After dosing, expired air, excreta, and tissues were analyzed for 14C activity, and metabolites in urine were isolated and identified. Approximately 64% of the administered 14C activity was eliminated as 14CO2 and about 24% was excreted in urine within 48 hr after a single po dose of radiolabeled PGMEA. Similarly, 53% was eliminated as 14CO2 and 26% was excreted in urine within 48 hr after the inhalation exposure. Propylene glycol, propylene glycol monomethyl ether (PGME), and the sulfate and glucuronide conjugates of PGME were identified as urinary metabolites after po dosing, as well as after inhalation exposure to PGMEA. The urinary metabolite profile and disposition of (14C)PGMEA were nearly identical to results previously obtained with propylene glycol monomethyl ether (PGME), indicating that PGMEA is rapidly and extensively hydrolyzed to PGME in vivo. A short-term vapor inhalation toxicity study in which male and female Fischer 344 rats and B6C3F1 mice were exposed to 0, 300, 1000, or 3000 ppm PGMEA confirmed that there were no substantial differences in the systemic effects of PGMEA as compared to PGME. However, histopathologic examination did reveal changes in the olfactory portions of the nasal mucosa of rats and mice exposed to PGMEA, which may be related to acetic acid resulting from hydrolysis of PGMEA in the nasal epithelium.

  8. Subchronic toxicity of inhaled technical grade 1,3-dichloropropene in rats and mice.

    PubMed

    Stott, W T; Young, J T; Calhoun, L L; Battjes, J E

    1988-08-01

    In order to provide a comprehensive subchronic inhalation toxicity study of the soil fumigant, technical grade 1,3-dichloropropene (DCPT), male and female Fischer 344 rats and B6C3F1 mice were exposed to 0, 10, 30, 90, or 150 ppm DCPT vapors 6 hr/day, 5 days/week for 13 weeks. The primary target tissues of inhaled DCPT were identified as the nasal mucosa of both sexes of rats and mice, and the urinary bladder of female mice. In addition, depressed growth rates of all animals exposed to 90 or 150 ppm DCPT (up to 20% in rats and 12% in mice) resulted in a variety of alterations in hematologic and clinical chemistry parameters, and changes in organ weights relative to controls. Nasal mucosal effects consisted of a dose-related slight degenerative effect of nasal olfactory epithelium or a mild hyperplasia of the respiratory epithelium or both in all animals exposed to 90 or 150 ppm and 2 of 10 male rats exposed to 30 ppm DCPT. Some focal areas of respiratory metaplasia were also noted in high exposure group mice. Urinary bladder effects consisted of a diffuse, moderate hyperplasia of the transitional epithelium in female mice exposed to 90 or 150 ppm DCPT. No treatment-related effects were observed in rats or mice exposed to 10 ppm DCPT vapors.

  9. Component-specific toxic concerns of the inhalable fraction of urban road dust.

    PubMed

    Potgieter-Vermaak, S; Rotondo, G; Novakovic, V; Rollins, S; Van Grieken, R

    2012-12-01

    Continuous global urbanisation causes an ever-growing ecological footprint of pollution. Road dust (RD), one of these pollutants, poses a health concern due to carcinogenic and toxic components potentially present in the micron-sized fractions. The literature reports on the concentrations of trace, toxic metals and metalloids present in RD (Hooker and Nathanail in Chem Geol 226:340-351, 2006), but the literature on its molecular composition is limited. Recent reports on the bioaccessibility of platinum group metals are also reported (Colombo et al. in Chem Geol 226:340-351, 2008). In vitro and animal toxicological studies confirmed that the chemical composition of inhaled particles plays a major role in its toxic, genotoxic and carcinogenic mechanisms, but the component-specific toxic effects are still not understood. Particle-bound airborne transition metals can also lead to the production of reactive oxygen species in lung tissue; a special concern amongst particularly susceptible cohorts (children and elderly). The characterisation of the molecular composition of the fine fraction is evidently of importance for public health. During a pilot study, partially characterised size-fractioned RD samples (Barrett et al. in Eviron Sci Technol 44:2940-2946, 2010) were analysed for their elemental concentration using X-ray fluorescence spectrometry and inductively coupled plasma mass spectrometry. In addition, separately dispersed particles (200 particles per size fraction) were analysed individually by means of computer-controlled electron probe X-ray micro-analysis (CC-EPXMA) and their molecular structure probed by studying elemental associations. These were correlated with micro-Raman spectroscopy (MRS) results. It was found that the fine fraction (<38 μm) had the highest Pb (238 ppm) and Cr (171 ppm) concentrations. The CC-EPXMA data showed >50 % association of Cr-rich particles with Pb, and the MRS data showed that the Cr was mostly present as lead chromate and

  10. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 3 2014-04-01 2014-04-01 false Schedule for 90-Day Sunset Reviews VIII Annex VIII... AND COUNTERVAILING DUTIES Pt. 351, Annex VIII-A Annex VIII-A to Part 351—Schedule for 90-Day Sunset Reviews Day 1 Event Regulation 0 Initiation § 351.218(c) 15 Filing of Notice of Intent to Participate...

  11. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 3 2012-04-01 2012-04-01 false Schedule for 90-Day Sunset Reviews VIII Annex VIII... AND COUNTERVAILING DUTIES Pt. 351, Annex VIII-A Annex VIII-A to Part 351—Schedule for 90-Day Sunset Reviews Day 1 Event Regulation 0 Initiation § 351.218(c) 15 Filing of Notice of Intent to Participate...

  12. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 3 2013-04-01 2013-04-01 false Schedule for 90-Day Sunset Reviews VIII Annex VIII... AND COUNTERVAILING DUTIES Pt. 351, Annex VIII-A Annex VIII-A to Part 351—Schedule for 90-Day Sunset Reviews Day 1 Event Regulation 0 Initiation § 351.218(c) 15 Filing of Notice of Intent to Participate...

  13. Odorless inhalant toxic encephalopathy in developing countries household: Gas geyser syndrome

    PubMed Central

    Mehta, Anish; Mahale, Rohan; John, Aju Abraham; Abbas, Masoom Mirza; Javali, Mahendra; Acharya, Purushottam; Rangasetty, Srinivasa

    2016-01-01

    Background: Liquefied petroleum gas geysers are used very frequently for heating water in developing countries such as India. However, these gas geysers emit various toxic gases; one among them is colorless, odorless carbon monoxide (CO). In the past few years, there were reports of unexplained loss of consciousness in the bathroom. However, the exact cause for these episodes has been recognized as toxic encephalopathy due to toxic gases inhalation mainly CO. Objective: To analyze the clinical profile and outcome of patients brought with loss of consciousness in the bathroom while bathing using gas geyser. Materials and Methods: Case records of patients with the diagnosis of gas geyser syndrome from 2013 to 2015 were retrieved and analyzed. Twenty-four cases were identified and included in the study. This was a retrospective, descriptive study. Results: Twenty-four patients were brought to our Emergency Department with loss of consciousness in the bathroom while bathing. Twenty-one cases had loss of consciousness during bathing and recovered spontaneously. Two cases were found dead in the bathroom and were brought to the Department of Forensic Medicine for postmortem. One case was brought in deep altered state of consciousness and succumbed to illness within 1 week. Conclusion: Awareness regarding CO intoxication due to usage of ill-fitted, ill-ventilated gas geyser is necessary as they are entirely preventable conditions. PMID:27114653

  14. Ethylene glycol monomethyl ether and propylene glycol monomethyl ether: metabolism, disposition, and subchronic inhalation toxicity studies

    SciTech Connect

    Miller, R.R.; Hermann, E.A.; Young, J.T.; Landry, T.D.; Calhoun, L.L.

    1984-08-01

    Short-term and subchronic vapor inhalation studies have shown that there are pronounced differences in the toxicological properties of ethylene glycol monomethyl ether (EGME) and propylene glycol monomethyl ether (PGME). Overexposure to EGME has resulted in adverse effects on testes, bone marrow and lymphoid tissues in laboratory animals. PGME does not affect these tissues, and instead, overexposure to PGME has been associated with increases in liver weight and central nervous system depression. EGME is primarily oxidized to methoxyacetic acid in male rats, while PGME apparently undergoes O-demethylation to form propylene glycol. Since methoxyacetic acid has been shown to have the same spectrum of toxicity as EGME in male rats, the observed differences in the toxicological properties of EGME and PGME are thought to be due to the fact that the two materials are biotransformed via different routes to different types of metabolites. 6 references, 3 figures, 12 tables.

  15. Airway irritation, inflammation, and toxicity in mice following inhalation of metal oxide nanoparticles

    PubMed Central

    Larsen, Søren T.; Jackson, Petra; Poulsen, Steen S.; Levin, Marcus; Jensen, Keld A.; Wallin, Håkan; Nielsen, Gunnar D.; Koponen, Ismo K.

    2016-01-01

    Abstract Metal oxide nanoparticles are used in a broad range of industrial processes and workers may be exposed to aerosols of the particles both during production and handling. Despite the widespread use of these particles, relatively few studies have been performed to investigate the toxicological effects in the airways following inhalation. In the present study, the acute (24 h) and persistent (13 weeks) effects in the airways after a single exposure to metal oxide nanoparticles were studied using a murine inhalation model. Mice were exposed 60 min to aerosols of either ZnO, TiO2, Al2O3 or CeO2 and the deposited doses in the upper and lower respiratory tracts were calculated. Endpoints were acute airway irritation, pulmonary inflammation based on analyses of bronchoalveolar lavage (BAL) cell composition, DNA damage assessed by the comet assay and pulmonary toxicity assessed by protein level in BAL fluid and histology. All studied particles reduced the tidal volume in a concentration-dependent manner accompanied with an increase in the respiratory rate. In addition, ZnO and TiO2 induced nasal irritation. BAL cell analyses revealed both neutrophilic and lymphocytic inflammation 24-h post-exposure to all particles except TiO2. The ranking of potency regarding induction of acute lung inflammation was Al2O3 = TiO2 < CeO2 ≪ ZnO. Exposure to CeO2 gave rise to a more persistent inflammation; both neutrophilic and lymphocytic inflammation was seen 13 weeks after exposure. As the only particles, ZnO caused a significant toxic effect in the airways while TiO2 gave rise to DNA-strand break as shown by the comet assay. PMID:27323801

  16. Airway irritation, inflammation, and toxicity in mice following inhalation of metal oxide nanoparticles.

    PubMed

    Larsen, Søren T; Jackson, Petra; Poulsen, Steen S; Levin, Marcus; Jensen, Keld A; Wallin, Håkan; Nielsen, Gunnar D; Koponen, Ismo K

    2016-11-01

    Metal oxide nanoparticles are used in a broad range of industrial processes and workers may be exposed to aerosols of the particles both during production and handling. Despite the widespread use of these particles, relatively few studies have been performed to investigate the toxicological effects in the airways following inhalation. In the present study, the acute (24 h) and persistent (13 weeks) effects in the airways after a single exposure to metal oxide nanoparticles were studied using a murine inhalation model. Mice were exposed 60 min to aerosols of either ZnO, TiO2, Al2O3 or CeO2 and the deposited doses in the upper and lower respiratory tracts were calculated. Endpoints were acute airway irritation, pulmonary inflammation based on analyses of bronchoalveolar lavage (BAL) cell composition, DNA damage assessed by the comet assay and pulmonary toxicity assessed by protein level in BAL fluid and histology. All studied particles reduced the tidal volume in a concentration-dependent manner accompanied with an increase in the respiratory rate. In addition, ZnO and TiO2 induced nasal irritation. BAL cell analyses revealed both neutrophilic and lymphocytic inflammation 24-h post-exposure to all particles except TiO2. The ranking of potency regarding induction of acute lung inflammation was Al2O3 = TiO2 < CeO2 ≪ ZnO. Exposure to CeO2 gave rise to a more persistent inflammation; both neutrophilic and lymphocytic inflammation was seen 13 weeks after exposure. As the only particles, ZnO caused a significant toxic effect in the airways while TiO2 gave rise to DNA-strand break as shown by the comet assay.

  17. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects... (retina, optic nerve). (C) Glandular system—adrenals, parathyroid, thyroid. (D) Respiratory system—trachea... hematopoietic system, reticulocyte counts and bone marrow cytology may be indicated. (D) Other...

  18. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects... (retina, optic nerve). (C) Glandular system—adrenals, parathyroid, thyroid. (D) Respiratory system—trachea... hematopoietic system, reticulocyte counts and bone marrow cytology may be indicated. (D) Other...

  19. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects... (retina, optic nerve). (C) Glandular system—adrenals, parathyroid, thyroid. (D) Respiratory system—trachea... hematopoietic system, reticulocyte counts and bone marrow cytology may be indicated. (D) Other...

  20. Five-day inhalation toxicity study of three types of synthetic amorphous silicas in Wistar rats and post-exposure evaluations for up to 3 months.

    PubMed

    Arts, Josje H E; Muijser, Hans; Duistermaat, Evert; Junker, Karin; Kuper, C Frieke

    2007-10-01

    Evidence suggests that short-term animal exposures to synthetic amorphous silicas (SAS) and crystalline silica can provide comparable prediction of toxicity to those of 90-day studies, therefore providing the opportunity to screen these types of substances using short-term rather than 90-day studies. To investigate this hypothesis, the inhalation toxicity of three SAS, precipitated silica Zeosil 45, silica gel Syloid 74, and pyrogenic silica Cab-O-Sil M5 was studied in Wistar rats. Rats were exposed nose-only to concentrations of 1, 5 or 25mg/m(3) of one of the SAS 6h a day for five consecutive days. Positive controls were exposed to 25mg/m(3) crystalline silica (quartz dust), negative controls to clean air. Animals were necropsied the day after the last exposure or 1 or 3 months later. All exposures were tolerated without serious clinical effects, changes in body weight or food intake. Differences in the effects associated with exposure to the three types of SAS were limited and almost exclusively confined to the 1-day post-exposure time point. Silicon levels in tracheobronchial lymph nodes were below the detection limit in all groups at all time points. Silicon was found in the lungs of all high concentration SAS groups 1-day post-exposure, and was cleared 3 months later. Exposure to all three SAS at 25mg/m(3) induced elevations in biomarkers of cytotoxicity in bronchoalveolar lavage fluid (BALf), increases in lung and tracheobronchial lymph node weight and histopathological lung changes 1-day post-exposure. Exposure to all three SAS at 5mg/m(3) induced histopathological changes and changes in BALf only. With all three SAS these effects were transient and, with the exception of slight histopathological lung changes at the higher exposure levels, were reversible during the 3-month recovery period. No adverse changes were observed in animals exposed to any of the SAS at 1mg/m(3). In contrast, with quartz-exposed animals the presence of silicon in the lungs was

  1. Acute inhalation toxicity of 3-methylfuran in the mouse: pathology, cell kinetics, and respiratory rate effects

    SciTech Connect

    Haschek, W.M.; Boyd, M.R.; Hakkinen, P.J.; Owenby, C.S.; Witschi, H.

    1984-01-01

    The acute inhalation toxicity of 3-methylfuran (3MF) was investigated in male BALB/c mice by morphologic examination of animals killed at varying timepoints following a 1-hr exposure to an initial chamber concentration of 14 to 37 mumol/liter (343 to 906 ppm). In addition, respiratory rate measurements and cell kinetics were used to assess quantitatively pulmonary damage and repair. Necrosis of nonciliated bronchiolar epithelial (Clara) cells was seen 1 day following exposure and was followed by regeneration, which was virtually complete, within 21 days. Cell kinetic studies showed peak bronchiolar cell proliferation at 3 days with a labeling index (LI) of 5.0% compared to 0.4% in controls. An increase in parenchymal cell proliferation was also noted coincident with a mild interstitial pneumonitis. This parenchymal proliferation, peaking at 10 days with an LI of 1.4% compared to 0.2% in controls, consisted primarily of type II epithelial and endothelial cell proliferation indicating possible delayed damage and repair of type I epithelial and endothelial cells. The respiratory rate showed an initial transient increase followed by a more prolonged decrease with eventual return to control levels. 3MF toxicity was also evidenced by a necrotizing suppurative rhinitis, centrilobular hepatic necrosis, lymphocyte necrosis in the thymus and spleen, sialoadenitis, and otitis media.

  2. Recombinant paraoxonase 1 protects against sarin and soman toxicity following microinstillation inhalation exposure in guinea pigs.

    PubMed

    Valiyaveettil, Manojkumar; Alamneh, Yonas; Rezk, Peter; Perkins, Michael W; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2011-05-10

    To explore the efficacy of paraoxonase 1 (PON1) as a catalytic bioscavenger, we evaluated human recombinant PON1 (rePON1) expressed in Trichoplusia ni larvae against sarin and soman toxicity using microinstillation inhalation exposure in guinea pigs. Animals were pretreated intravenously with catalytically active rePON1, followed by exposure to 1.2 X LCt₅₀ sarin or soman. Administration of 5 units of rePON1 showed mild increase in the blood activity of the enzyme after 30 min, but protected the animals with a significant increase in survival rate along with minimal signs of nerve agent toxicity. Recombinant PON1 pretreated animals exposed to sarin or soman prevented the reduction of blood O₂ saturation and pulse rate observed after nerve agent exposure. In addition, rePON1 pretreated animals showed significantly higher blood PON1, acetylcholinesterase (AChE), and butyrylcholinesterase activity after nerve agent exposure compared to the respective controls without treatments. AChE activity in different brain regions of rePON1 pretreated animals exposed to sarin or soman were also significantly higher than respective controls. The remaining activity of blood PON1, cholinesterases and brain AChE in PON1 pretreated animals after nerve agent exposure correlated with the survival rate. In summary, these data suggest that human rePON1 protects against sarin and soman exposure in guinea pigs.

  3. 90-day postoperative mortality is a legitimate measure of hepatopancreatobiliary surgical quality

    PubMed Central

    Mise, Yoshihiro; Vauthey, Jean-Nicolas; Zimmitti, Giuseppe; Parker, Nathan H.; Conrad, Claudius; Aloia, Thomas A.; Lee, Jeffery E.; Fleming, Jason B.; Katz, Matthew H. G.

    2015-01-01

    Objective To investigate the legitimacy of 90-day mortality as a measure of hepatopancreatobiliary quality. Summary Background Data The 90-day mortality rate has been increasingly but not universally reported after hepatopancreatobiliary surgery. The legitimacy of this definition as a measure of surgical quality has not been evaluated. Methods We retrospectively reviewed the causes of all deaths that occurred within 365 postoperative days in patients undergoing hepatectomy (n = 2811) and/or pancreatectomy (n = 1092) from January 1997 through December 2012. The rates of surgery-related, disease-related, and overall mortality within 30 days, within 30 days or during the index hospitalization, within 90 days, and within 180 days following surgery were calculated. Results Seventy-nine (3%) surgery-related deaths and 92 (3%) disease-related deaths occurred within 365 days after hepatectomy. Twenty (2%) surgery-related deaths and 112 (10%) disease-related deaths occurred within 365 days after pancreatectomy. The overall mortality rates at 99 day and 118 days optimally reflected surgery-related mortality following hepatobiliary and pancreatic operations, respectively. The 90-day overall mortality rate was a less sensitive but equivalently specific measure of surgery-related death. Conclusions and Relevance The 99-day and 118-day definitions of postoperative mortality optimally reflected surgery-related mortality following hepatobiliary and pancreatic operations, respectively. However, among commonly reported metrics, the 90-day overall mortality rate represents a legitimate measure of surgical quality. PMID:25590497

  4. A 90-day study of three bruchid-resistant mung bean cultivars in Sprague-Dawley rats.

    PubMed

    Yao, Yang; Cheng, Xuzhen; Ren, Guixing

    2015-02-01

    Mung bean has been traditionally and widely used as an edible and medicinal plant in the South and Southeast Asia. Bruchid resistance mung bean has more potential in commercial use, but scarcely been evaluated for safety through standard in vivo toxicological studies. In the present study, subchronic oral toxicity studies of bruchid-resistant mung bean were designed and conducted in Sprague-Dawley (SD) rats for 90 days. During the subchronic oral toxicity study, no mortality and toxicologically significant changes in clinical signs, food consumption, opthalmoscopic examination, hematology, clinical biochemistry, macroscopic findings, organ weights and histopathological examination were noted in animal administered diet containing bruchid-resistant mung bean. These results demonstrated that bruchid resistant mung bean is as safe as conventional mung bean.

  5. Subchronic (12-week) inhalation toxicity study of methanol-fueled engine exhaust in rats

    SciTech Connect

    Maejima, Kazuhito; Suzuki, Tadao ); Numata, Hiroaki ); Maekawa, Akihiko ); Nagase, Sumi ); Ishinishi, Noburu )

    1994-01-01

    To evaluate the inhalation toxicity to rats of exhaust at low concentration for longer periods, Fischer 344 rats were exposed to 3 concentrations of exhaust generated by an M85 methanol-fueled engine (methanol with 15% gasoline) without catalyst for 8 h/d, 6 d/wk for 4, 8, or 12 wk. Concentration- and time-dependent increase carboxyhemoglobin in the erythrocytes and decrease in cytochrome P-450 in the lungs were observed in all treated groups. Furthermore, significant increases in plasma formaldehyde were observed in the group exposed to the highest concentration of exhaust (carbon monoxide, 89.8 ppm; formaldehyde, 2.3 ppm; methanol, 8.1 ppm; nitrogen oxides, 22.9 ppm; nitrogen dioxide, 1.1 ppm) for 8 or 12 wk. No change of plasma folic acid was observed in any group, and no methanol or formic acid was detected in the plasma in any animals. Histopathologically, exposure-related changes were found only in the nasal cavity of the high-concentration group. Slight hyperplasia/squamous metaplasias of the respiratory epithelium lining the nasoturbinate and maxilloturbinate were observed after 4 wk of exposure, and the incidences and degrees of these lesions increased slightly with the exposure time. No changes were found in the olfactory epithelium of the nasal cavity. As judged by optical microscopy, the exhaust concentration with no effect on the nasal cavity under the experimental conditions was concluded to be the medium concentration level containing 0.55 ppm formaldehyde. In the present study, however, concentration- and time-dependent increase of carboxyhemoglobin in the erythrocytes and decrease of the lung P-450 level were observed. Therefore, further study on more long-term inhalation of lower concentrations of exhaust might be needed. 31 refs., 2 figs., 3 tabs.

  6. Acute pulmonary toxicity following inhalation exposure to aerosolized VX in anesthetized rats.

    PubMed

    Peng, Xinqi; Perkins, Michael W; Simons, Jannitt; Witriol, Alicia M; Rodriguez, Ashley M; Benjamin, Brittany M; Devorak, Jennifer; Sciuto, Alfred M

    2014-06-01

    This study evaluated acute toxicity and pulmonary injury in rats at 3, 6 and 24 h after an inhalation exposure to aerosolized O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX). Anesthetized male Sprague-Dawley rats (250-300 g) were incubated with a glass endotracheal tube and exposed to saline or VX (171, 343 and 514 mg×min/m³ or 0.2, 0.5 and 0.8 LCt₅₀, respectively) for 10 min. VX was delivered by a small animal ventilator at a volume of 2.5 ml × 70 breaths/minute. All VX-exposed animals experienced a significant loss in percentage body weight at 3, 6, and 24 h post-exposure. In comparison to controls, animals exposed to 514 mg×min/m³ of VX had significant increases in bronchoalveolar lavage (BAL) protein concentrations at 6 and 24 h post-exposure. Blood acetylcholinesterase (AChE) activity was inhibited dose dependently at each of the times points for all VX-exposed groups. AChE activity in lung homogenates was significantly inhibited in all VX-exposed groups at each time point. All VX-exposed animals assessed at 20 min and 3, 6 and 24 h post-exposure showed increases in lung resistance, which was prominent at 20 min and 3 h post-exposure. Histopathologic evaluation of lung tissue of the 514 mg×min/m³ VX-exposed animals at 3, 6 and 24 h indicated morphological changes, including perivascular inflammation, alveolar exudate and histiocytosis, alveolar septal inflammation and edema, alveolar epithelial necrosis, and bronchiolar inflammatory infiltrates, in comparison to controls. These results suggest that aerosolization of the highly toxic, persistent chemical warfare nerve agent VX results in acute pulmonary toxicity and lung injury in rats.

  7. Rifapentine-Proliposomes for Inhalation: In Vitro and In Vivo Toxicity

    PubMed Central

    Patil-Gadhe, Arpana A.; Kyadarkunte, Abhay Y.; Pereira, Michael; Jejurikar, Gauri; Patole, Milind S.; Risbud, Arun; Pokharkar, Varsha B.

    2014-01-01

    Background: Oral therapy for pulmonary tuberculosis (TB) treatment suffers from the limitation of hepatic metabolism leading insufficient concentration of antitubercular (anti-TB) drugs in alveolar macrophage which harbors Mycobacterium tuberculosis (MTB). Targeted aerosol delivery of antituberculous drug to lung is efficient for treating local lung TB infection. Objective: The present study was aimed to evaluate rifapentine (RPT) loaded proliposomal dry powder for inhalation (RLDPI) for anti-TBactivity and cytotoxicity in vitro. In vivo toxicity study was also undertaken in Wistar rats to determine safe concentration of RLDPI for administration. Materials and Methods: Anti-TB activity of developed RLDPI was assessed using drug susceptibility testing (DST) on Mycobacteria growth indicator tube (MGIT) method. In vitro cytotoxicity was performed in A549 cell lines and IC50 values were used to compare the cytotoxicity of formulation with pure RPT. In vivo repeated dose toxicity study was undertaken using Wistar rats at three different doses for 28-days by intratracheal insufflations method. Results: The results of DST study revealed sensitivity of tubercle bacteria to RLDPI at concentration equivalent to 10 μg/mL of RPT. This study confirmed anti-TB potential of RPT in spray-dried RLDPI, though the spray drying method is reported to reduce activity of drugs. Cytotoxicity study in A549 cells demonstrated that RPT when encapsulated in liposomes as RLDPI was safe to cells as compared to pure RPT. In vivo toxicity study revealed that RPT in the form of RLDPI was safe at 1 and 5 mg/kg dose. However, mortality was seen at higher dose (10 mg/kg), possibly because of liver and kidney damage. Conclusion: Thus, these studies demonstrated safety of RLDPI for the treatment of pulmonary TB. PMID:25948966

  8. Comparative inhalation toxicity of multi-wall carbon nanotubes, graphene, graphite nanoplatelets and low surface carbon black

    PubMed Central

    2013-01-01

    Background Carbon nanotubes, graphene, graphite nanoplatelets and carbon black are seemingly chemically identical carbon-based nano-materials with broad technological applications. Carbon nanotubes and carbon black possess different inhalation toxicities, whereas little is known about graphene and graphite nanoplatelets. Methods In order to compare the inhalation toxicity of the mentioned carbon-based nanomaterials, male Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 hours per day on 5 consecutive days. Target concentrations were 0.1, 0.5, or 2.5 mg/m3 for multi-wall carbon nanotubes and 0.5, 2.5, or 10 mg/m3 for graphene, graphite nanoplatelets and low-surface carbon black. Toxicity was determined after end of exposure and after three-week recovery using broncho-alveolar lavage fluid and microscopic examinations of the entire respiratory tract. Results No adverse effects were observed after inhalation exposure to 10 mg/m3 graphite nanoplatelets or relatively low specific surface area carbon black. Increases of lavage markers indicative for inflammatory processes started at exposure concentration of 0.5 mg/m3 for multi-wall carbon nanotubes and 10 mg/m3 for graphene. Consistent with the changes in lavage fluid, microgranulomas were observed at 2.5 mg/m3 multi-wall carbon nanotubes and 10 mg/m3 graphene. In order to evaluate volumetric loading of the lung as the key parameter driving the toxicity, deposited particle volume was calculated, taking into account different methods to determine the agglomerate density. However, the calculated volumetric load did not correlate to the toxicity, nor did the particle surface burden of the lung. Conclusions The inhalation toxicity of the investigated carbon-based materials is likely to be a complex interaction of several parameters. Until the properties which govern the toxicity are identified, testing by short-term inhalation is the best option to identify hazardous properties in

  9. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    PubMed Central

    2014-01-01

    Background Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Methods Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. Results An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Conclusions Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post

  10. 26 CFR 54.9815-2708 - Prohibition on waiting periods that exceed 90 days.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... days. 54.9815-2708 Section 54.9815-2708 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... on waiting periods that exceed 90 days. (a) General rule. A group health plan, and a health insurance issuer offering group health insurance coverage, must not apply any waiting period that exceeds 90...

  11. Implications of the 90-day episode definition used for the Comprehensive Care for Joint Replacement model

    PubMed Central

    Ellimoottil, Chad; Ryan, Andrew M.; Hou, Hechuan; Dupree, James M.; Hallstrom, Brian; Miller, David C.

    2017-01-01

    Importance Under the Comprehensive Care for Joint Replacement (CJR) model, hospitals are held accountable for nearly all Medicare payments that occur during the initial hospitalization through 90-days post-discharge (i.e., episode of care). It is unknown whether unrelated expenditures resulting from this “broad” episode definition will impact participating hospital’s average 90-day episode payments. Objective To compare the CJR program’s broad episode definition to a clinically-narrow episode definition Design We identified Medicare claims for patients in Michigan who underwent joint replacement from 2011 through 2013. Using specifications from the CJR model and the clinically-narrow Hospital Compare payment measure, we constructed episodes of care and calculated 90-day episode payments. We then compared hospitals’ average 90-day episode payments using the two episode definitions and fit linear regression models to understand whether payment differences were associated with specific hospital characteristics (average CMS-HCC risk score, rural hospital status, joint replacement volume, percentage of Medicaid discharges, teaching hospital status, number of beds, percentage of joint replacements performed on African American patients and median income of the hospital’s county). Setting All Michigan hospitals located in metropolitan statistical areas Participants Medicare beneficiaries Main Outcome and Measure(s) The correlation and difference between average 90-day episode payments using the broad CJR model episode definition and the clinically-narrow Hospital Compare episode definition. Results We identified 23,251 joint replacement episodes. 90-day episode payments using the broad CJR episode definition ranged from $17,349 to $29,465 (mean: $22,122, standard deviation: $2,600). Episode payments were slightly lower (mean: $21,670) when the Hospital Compare episode definition was used. Both methods were strongly correlated (r=0.99, p<0.001). The average

  12. Health assessment of gasoline and fuel oxygenate vapors: subchronic inhalation toxicity.

    PubMed

    Clark, Charles R; Schreiner, Ceinwen A; Parker, Craig M; Gray, Thomas M; Hoffman, Gary M

    2014-11-01

    Sprague Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess whether their use in gasoline influences the hazard of evaporative emissions. Test substances included vapor condensates prepared from an EPA described "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/m(3) and exposures were for 6h/day, 5days/week for 13weeks. A portion of the animals were maintained for a four week recovery period to determine the reversibility of potential adverse effects. Increased kidney weight and light hydrocarbon nephropathy (LHN) were observed in treated male rats in all studies which were reversible or nearly reversible after 4weeks recovery. LHN is unique to male rats and is not relevant to human toxicity. The no observed effect level (NOAEL) in all studies was 10,000mg/m(3), except for G/MTBE (<2000) and G/TBA (2000). The results provide evidence that use of the studied oxygenates are unlikely to increase the hazard of evaporative emissions during refueling, compared to those from gasoline alone.

  13. Assessment of Pulmonary Toxicity Induced by Inhaled Toner with External Additives.

    PubMed

    Tomonaga, Taisuke; Izumi, Hiroto; Yoshiura, Yukiko; Myojo, Toshihiko; Oyabu, Takako; Lee, Byeong-Woo; Okada, Takami; Li, Yunshan; Kawai, Kazuaki; Higashi, Toshiaki; Morimoto, Yasuo

    2017-01-01

    We investigated the harmful effects of exposure to a toner with external additives by a long-term inhalation study using rats, examining pulmonary inflammation, oxidative stress, and histopathological changes in the lung. Wistar rats were exposed to a well-dispersed toner (mean of MMAD: 2.1 μm) at three mass concentrations of 1, 4, and 16 mg/m(3) for 22.5 months, and the rats were sacrificed after 6 months, 12 months, and 22.5 months of exposure. The low and medium concentrations did not induce statistically significant pulmonary inflammation, but the high concentration did, and, in addition, a histopathological examination showed fibrosis in the lung. Although lung tumor was observed in one sample of high exposure for 22.5 months, the cause was not statistically significant. On the other hand, a persistent increase in 8-OHdG was observed in the high exposure group, indicating that DNA damage by oxidative stress with persistent inflammation leads to the formation of tumorigenesis. The results of our studies show that toners with external additives lead to pulmonary inflammation, oxidative stress, and fibrosis only at lung burdens beyond overload. These data suggest that toners with external additives may have low toxicity in the lung.

  14. Assessment of Pulmonary Toxicity Induced by Inhaled Toner with External Additives

    PubMed Central

    Yoshiura, Yukiko; Myojo, Toshihiko; Oyabu, Takako; Lee, Byeong-Woo; Okada, Takami; Li, Yunshan; Higashi, Toshiaki

    2017-01-01

    We investigated the harmful effects of exposure to a toner with external additives by a long-term inhalation study using rats, examining pulmonary inflammation, oxidative stress, and histopathological changes in the lung. Wistar rats were exposed to a well-dispersed toner (mean of MMAD: 2.1 μm) at three mass concentrations of 1, 4, and 16 mg/m3 for 22.5 months, and the rats were sacrificed after 6 months, 12 months, and 22.5 months of exposure. The low and medium concentrations did not induce statistically significant pulmonary inflammation, but the high concentration did, and, in addition, a histopathological examination showed fibrosis in the lung. Although lung tumor was observed in one sample of high exposure for 22.5 months, the cause was not statistically significant. On the other hand, a persistent increase in 8-OHdG was observed in the high exposure group, indicating that DNA damage by oxidative stress with persistent inflammation leads to the formation of tumorigenesis. The results of our studies show that toners with external additives lead to pulmonary inflammation, oxidative stress, and fibrosis only at lung burdens beyond overload. These data suggest that toners with external additives may have low toxicity in the lung. PMID:28191462

  15. A 90-Day Tenofovir Reservoir Intravaginal Ring for Mucosal HIV Prophylaxis

    PubMed Central

    Johnson, Todd J.; Clark, Meredith R.; Albright, Theodore H.; Nebeker, Joel S.; Tuitupou, Anthony L.; Clark, Justin T.; Fabian, Judit; McCabe, R. Tyler; Chandra, Neelima; Doncel, Gustavo F.; Friend, David R.

    2012-01-01

    A vaginal gel containing the antiretroviral tenofovir (TFV) recently demonstrated 39% protection against HIV infection in women. We designed and evaluated a novel reservoir TFV intravaginal ring (IVR) to potentially improve product effectiveness by providing a more controlled and sustained vaginal dose to maintain cervicovaginal concentrations. Polyurethane tubing of various hydrophilicities was filled with a high-density TFV/glycerol/water semisolid paste and then end-sealed to create IVRs. In vitro, TFV release increased with polyurethane hydrophilicity, with 35 weight percent water-swelling polyurethane IVRs achieving an approximately 10-mg/day release for 90 days with mechanical stiffness similar to that of the commercially available NuvaRing. This design was evaluated in two 90-day in vivo sheep studies for TFV pharmacokinetics and safety. Overall, TFV vaginal tissue, vaginal fluid, and plasma levels were relatively time independent over the 90-day duration at approximately 104 ng/g, 106 ng/g, and 101 ng/ml, respectively, near or exceeding the highest observed concentrations in a TFV 1% gel control group. TFV vaginal fluid concentrations were approximately 1,000-fold greater than levels shown to provide significant protection in women using the TFV 1% gel. There were no toxicological findings following placebo and TFV IVR treatment for 28 or 90 days, although slight to moderate increases in inflammatory infiltrates in the vaginal epithelia were observed in these animals compared to naïve animals. In summary, the controlled release of TFV from this reservoir IVR provided elevated sheep vaginal concentrations for 90 days to merit its further evaluation as an HIV prophylactic. PMID:23006751

  16. Acute and subchronic toxicity of inhaled toluene in male Long Evans rats: oxidative stress markers in brain

    EPA Pesticide Factsheets

    Research interested in oxidative stress markers following exposure to VOCsThis dataset is associated with the following publication:Kodavanti , P., J. Royland , D.A. Moore-Smith, J. Beas, J. Richards , T. Beasley , P. Evansky , and P.J. Bushnell. Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain. NEUROTOXICOLOGY. Elsevier B.V., Amsterdam, NETHERLANDS, 51: 10-19, (2015).

  17. Asphyxial deaths caused by automobile exhaust inhalation not attributable to carbon monoxide toxicity: study of 2 cases.

    PubMed

    Schmunk, Gregory A; Kaplan, James A

    2002-06-01

    The authors report two suicides that resulted from the intentional inhalation of automobile exhaust gases in which death occurred without the formation of physiologically significant amounts of carboxyhemoglobin. These circumstances are correlated with measurements of the involved vehicles' exhaust gases, which showed reduced concentrations of carbon monoxide present, reflecting improvements in automobile engine technology. In the absence of carbon monoxide toxicity, the authors attribute death in these cases to asphyxia caused by carbon dioxide intoxication and diminished atmospheric oxygen concentrations.

  18. Preoperative risk score predicting 90-day mortality after liver resection in a population-based study.

    PubMed

    Chang, Chun-Ming; Yin, Wen-Yao; Su, Yu-Chieh; Wei, Chang-Kao; Lee, Cheng-Hung; Juang, Shiun-Yang; Chen, Yi-Ting; Chen, Jin-Cherng; Lee, Ching-Chih

    2014-09-01

    The impact of important preexisting comorbidities, such as liver and renal disease, on the outcome of liver resection remains unclear. Identification of patients at risk of mortality will aid in improving preoperative preparations. The purpose of this study is to develop and validate a population-based score based on available preoperative and predictable parameters predicting 90-day mortality after liver resection using data from a hepatitis endemic country.We identified 13,159 patients who underwent liver resection between 2002 and 2006 in the Taiwan National Health Insurance Research Database. In a randomly selected half of the total patients, multivariate logistic regression analysis was used to develop a prediction score for estimating the risk of 90-day mortality by patient demographics, preoperative liver disease and comorbidities, indication for surgery, and procedure type. The score was validated with the remaining half of the patients.Overall 90-day mortality was 3.9%. Predictive characteristics included in the model were age, preexisting cirrhosis-related complications, ischemic heart disease, heart failure, cerebrovascular disease, renal disease, malignancy, and procedure type. Four risk groups were stratified by mortality scores of 1.1%, 2.2%, 7.7%, and 15%. Preexisting renal disease and cirrhosis-related complications were the strongest predictors. The score discriminated well in both the derivation and validation sets with c-statistics of 0.75 and 0.75, respectively.This population-based score could identify patients at risk of 90-day mortality before liver resection. Preexisting renal disease and cirrhosis-related complications had the strongest influence on mortality. This score enables preoperative risk stratification, decision-making, quality assessment, and counseling for individual patients.

  19. A two-generation inhalation reproductive toxicity study upon the exposure to manganese chloride.

    PubMed

    McGough, Doreen; Jardine, Lynne

    2017-01-01

    A number of published studies have suggested that high levels of exposure to manganese, especially those found in occupational settings, can adversely affect the reproductive system. The objective of this study was therefore to investigate if these findings can be replicated using the Sprague Dawley rat and, if so, to identify those parts of the reproductive system are more susceptible. Male and female rats were exposed to manganese dichloride (MnCl2) via inhalation at concentrations of 0 (air-control); 5, 10 and 20μg/L air over 10 weeks (F0) and over 11 weeks (F1) prior to mating, and then throughout mating, gestation and lactation until termination after the F1 and F2 generation had reached Day 21 of lactation respectively. Animals were monitored for clinical signs of toxicity and for effects on body weight, food consumption, effects on the entire reproductive system including maternal care. The offspring were monitored for survival and growth up to weaning. Blood samples were taken from all adult animals for bioanalytical of manganese analysis prior to dosing, prior to mating and prior to weaning/necropsy. There were no deaths related to treatment, though respiratory tract effects were observed in F0 animals in the mid and high dose animals. Body weight and food consumption were affected at high dose in both generation. There were no treatment-related effects on the oestrous cycles, mating performance, sexual maturity, fertility or duration of gestation or litter size, the sperm motility, count of morphology (sperm) or the ovary follicle scoring in either generation. The No Observed Effect Level (NOEL) for reproductive performance was considered to be the target dose level of 20μg/L. Based on these findings, manganese chloride could not be considered a reprotoxicant under these conditions of exposure. Therefore, soluble and insoluble forms of inorganic manganese compounds by extrapolation cannot be considered as reprotoxicants.

  20. Carbon capture and sequestration: an exploratory inhalation toxicity assessment of amine-trapping solvents and their degradation products.

    PubMed

    McDonald, Jacob D; Kracko, Dean; Doyle-Eisele, Melanie; Garner, C Edwin; Wegerski, Chris; Senft, Al; Knipping, Eladio; Shaw, Stephanie; Rohr, Annette

    2014-09-16

    Carbon dioxide (CO2) absorption with aqueous amine solvents is a method of carbon capture and sequestration (CCS) from flue gases. One concern is the possible release of amine solvents and degradation products into the atmosphere, warranting evaluation of potential pulmonary effects from inhalation. The CCS amines monoethanolamine (MEA), methyldiethanolamine (MDEA), and piperazine (PIP) underwent oxidative and CO2-mediated degradation for 75 days. C57bl/6N mice were exposed for 7 days by inhalation of 25 ppm neat amine or equivalant concentration in the degraded mixture. The aqueous solutions were nebulized to create the inhalation atmospheres. Pulmonary response was measured by changes in inflammatory cells in bronchoalveolar lavage fluid and cytokine expression in lung tissue. Ames mutagenicity and CHO-K1 micronucleus assays were applied to assess genotoxicity. Chemical analysis of the test atmosphere and liquid revealed complex mixtures, including acids, aldehydes, and other compounds. Exposure to oxidatively degraded MEA increased (p < 0.05) total cells, neutrophils, and lymphocytes compared to control mice and caused inflammatory cytokine expression (statistical increase at p < 0.05). MEA and CO2-degraded MEA were the only atmospheres to show statistical (p < 0.05) increase in oxidative stress. CO2 degradation resulted in a different composition, less degradation, and lower observed toxicity (less magnitude and number of effects) with no genotoxicity. Overall, oxidative degradation of the amines studied resulted in enhanced toxicity (increased magnitude and number of effects) compared to the neat chemicals.

  1. Bioaccumulation and locomotor effects of manganese sulfate in Sprague-Dawley rats following subchronic (90 days) inhalation exposure

    SciTech Connect

    Tapin, Danielle; Kennedy, Greg; Lambert, Jean; Zayed, Joseph . E-mail: joseph.zayed@umontreal.ca

    2006-03-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic compound that was introduced as an antiknock additive to replace lead in unleaded fuel. The combustion of MMT results in the emission of fine Mn particulates mainly in the form of manganese sulfate and manganese phosphate. The objective of this study is to determine the effects of subchronic exposure to Mn sulfate in different tissues, on locomotor activity, on neuropathology, and on blood serum biochemical parameters. A control group and three groups of 30 male Sprague-Dawley rats were exposed 6-h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 {mu}g/m{sup 3} Mn sulfate. Locomotor activity was measured during 36 h using an Auto-Track System. Blood and the following tissues were collected and analyzed for manganese content by neutron activation analysis: olfactory bulb, globus pallidus, caudate/putamen, cerebellum, frontal cortex, liver, lung, testis, and kidney. Neuronal cell counts were obtained for the caudate/putamen and the globus pallidus and clinical biochemistry was assessed. Manganese concentrations were increased in blood, kidney, lung, and testis and in all brain regions in the 3000 {mu}g/m{sup 3} exposure group. Significant differences were also noted in the 300 {mu}g/m{sup 3} exposure group. Neuronal cell counts for the globus pallidus were significantly different between the two highest exposed groups and the controls. Locomotor activity for all exposure concentrations and resting time for the middle and highest concentrations for the two night resting periods were significantly increased. Total ambulatory count was decreased significantly for all exposure concentrations. Biochemical profiles also presented significant differences. No body weight loss was observed between all groups. These results suggest that neurotoxicity could occur at low exposure levels of Mn sulfate, one of the main combustion products of MMT.

  2. Influence of agglomeration and specific lung lining lipid/protein interaction on short-term inhalation toxicity.

    PubMed

    Wohlleben, Wendel; Driessen, Marc D; Raesch, Simon; Schaefer, Ulrich F; Schulze, Christine; Vacano, Bernhard von; Vennemann, Antje; Wiemann, Martin; Ruge, Christian A; Platsch, Herbert; Mues, Sarah; Ossig, Rainer; Tomm, Janina M; Schnekenburger, Jürgen; Kuhlbusch, Thomas A J; Luch, Andreas; Lehr, Claus-Michael; Haase, Andrea

    2016-09-01

    Lung lining fluid is the first biological barrier nanoparticles (NPs) encounter during inhalation. As previous inhalation studies revealed considerable differences between surface functionalized NPs with respect to deposition and toxicity, our aim was to investigate the influence of lipid and/or protein binding on these processes. Thus, we analyzed a set of surface functionalized NPs including different SiO2 and ZrO2 in pure phospholipids, CuroSurf(TM) and purified native porcine pulmonary surfactant (nS). Lipid binding was surprisingly low for pure phospholipids and only few NPs attracted a minimal lipid corona. Additional presence of hydrophobic surfactant protein (SP) B in CuroSurf(TM) promoted lipid binding to NPs functionalized with Amino or PEG residues. The presence of the hydrophilic SP A in nS facilitated lipid binding to all NPs. In line with this the degree of lipid and protein affinities for different surface functionalized SiO2 NPs in nS followed the same order (SiO2 Phosphate ∼ unmodified SiO2 < SiO2 PEG < SiO2 Amino NPs). Agglomeration and biomolecule interaction of NPs in nS was mainly influenced by surface charge and hydrophobicity. Toxicological differences as observed in short-term inhalation studies (STIS) were mainly influenced by the core composition and/or surface reactivity of NPs. However, agglomeration in lipid media and lipid/protein affinity appeared to play a modulatory role on short-term inhalation toxicity. For instance, lipophilic NPs like ZrO2, which are interacting with nS to a higher extent, exhibited a far higher lung burden than their hydrophilic counterparts, which deserves further attention to predict or model effects of respirable NPs.

  3. Multisite Study of an Implanted Continuous Glucose Sensor Over 90 Days in Patients With Diabetes Mellitus

    PubMed Central

    Dehennis, Andrew; Mortellaro, Mark A.; Ioacara, Sorin

    2015-01-01

    Background: Continuous glucose monitoring (CGM), which enables real-time glucose display and trend information as well as real-time alarms, can improve glycemic control and quality of life in patients with diabetes mellitus. Previous reports have described strategies to extend the useable lifetime of a single sensor from 1-2 weeks to 28 days. The present multisite study describes the characterization of a sensing platform achieving 90 days of continuous use for a single, fully implanted sensor. Method: The Senseonics CGM system is composed of a long-term implantable glucose sensor and a wearable smart transmitter. Study subjects underwent subcutaneous implantation of sensors in the upper arm. Eight-hour clinic sessions were performed every 14 days, during which sensor glucose values were compared against venous blood lab reference measurements collected every 15 minutes using mean absolute relative differences (MARDs). Results: All subjects (mean ± standard deviation age: 43.5 ± 11.0 years; with 10 sensors inserted in men and 14 in women) had type 1 diabetes mellitus. Most (22 of 24) sensors reported glucose values for the entire 90 days. The MARD value was 11.4 ± 2.7% (range, 8.1-19.5%) for reference glucose values between 40-400 mg/dl. There was no significant difference in MARD throughout the 90-day study (P = .31). No serious adverse events were noted. Conclusions: The Senseonics CGM, composed of an implantable sensor, external smart transmitter, and smartphone app, is the first system that uses a single sensor for continuous display of accurate glucose values for 3 months. PMID:26224762

  4. Human exploration of space: A review of NASA's 90-day study and alternatives

    NASA Technical Reports Server (NTRS)

    Stever, H. Guyford; Cannon, Robert H., Jr.; Gavin, Joseph G.; Kerrebrock, Jack L.; Lanzerotti, Louis J.; Levinthal, Elliott C.; Mar, James W.; Mcelroy, John H.; Mcruer, Duane T.; Merrell, William J., Jr.

    1990-01-01

    The National Research Council (NRC) examines the NASA Report of the 90-Day Study on Human Exploration of the Moon and Mars, and alternative concepts. Included in this paper, prepared for the National Space Council, are the answers to a challenging set of questions posed by the Vice President. Concerns addressed include: the appropriate pace, the scope of human exploration, the level of long-term support required, the technology development available and needed, the feasibility of long-duration human spaceflight in a low-gravity environment, scientific objectives, and other considerations such as costs and risks.

  5. 77 FR 45571 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To Delist the Green Turtle in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-01

    ...; 90-Day Finding on a Petition To Delist the Green Turtle in Hawaii and Notice of Status Review AGENCY...: We, NMFS, announce a 90-day finding on a petition to identify the Hawaiian population of the green... Species Act (ESA). The green turtle was listed under the ESA on July 28, 1978. Breeding populations of...

  6. 75 FR 67341 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Bay...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-02

    ... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Bay Springs Salamander as Endangered AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice of 90-day petition finding. SUMMARY: We, the U.S. Fish and Wildlife...

  7. 76 FR 61825 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List 29 Mollusk...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-05

    ... and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List 29 Mollusk Species as... CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List 29... term ``species'' to include ``any subspecies of fish or wildlife or plants, and any distinct...

  8. Pulmonary toxicity of nanomaterials: a critical comparison of published in vitro assays and in vivo inhalation or instillation studies.

    PubMed

    Landsiedel, Robert; Sauer, Ursula G; Ma-Hock, Lan; Schnekenburger, Jürgen; Wiemann, Martin

    2014-11-01

    To date, guidance on how to incorporate in vitro assays into integrated approaches for testing and assessment of nanomaterials is unavailable. In addressing this shortage, this review compares data from in vitro studies to results from in vivo inhalation or intratracheal instillation studies. Globular nanomaterials (ion-shedding silver and zinc oxide, poorly soluble titanium dioxide and cerium dioxide, and partly soluble amorphous silicon dioxide) and nanomaterials with higher aspect ratios (multiwalled carbon nanotubes) were assessed focusing on the Organisation for Economic Co-Operation and Development (OECD) reference nanomaterials for these substances. If in vitro assays are performed with dosages that reflect effective in vivo dosages, the mechanisms of nanomaterial toxicity can be assessed. In early tiers of integrated approaches for testing and assessment, knowledge on mechanisms of toxicity serves to group nanomaterials thereby reducing the need for animal testing.

  9. SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: IMMUNOLOGY, CARDIAC GENE EXPRESSION AND MARKERS OF OXIDATIVE STRESS.

    EPA Science Inventory

    The health effects of long-term exposure to volatile organic compounds (VOCs) are poorly understood, due primarily to insufficient human exposure data and inconsistent animal models. To develop a rodent model of long-term exposure to VOCs, a sub-chronic inhalation study with mult...

  10. SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: OXIDATIVE STRESS MARKERS IN BRAIN.

    EPA Science Inventory

    The effects of long-term exposure to volatile organic compounds (VOCs), which is of concern to the EPA, are poorly understood, primarily due to insufficient information about human exposure and unreliable animal models. A sub-chronic inhalation study with multiple endpoints was c...

  11. Ultrastructural response of rat lung to 90 days' exposure to oxygen at 450 mm Hg

    NASA Technical Reports Server (NTRS)

    Harrison, G. A.

    1974-01-01

    Young Sprague-Dawley rats were exposed to 100% oxygen at 450 mm Hg in constant environment capsules for 90 days. Lung tissue examined by electron microscopy revealed a number of changes, many similar to those observed after exposure to oxygen at 760 mm Hg for shorter periods of time. Alterations in vesicle size and number and in mitochondrial matrix and cristae appear in both the endothelial and epithelial cells. Blebbing and rarefication of cytoplasm occur in both cell layers of the alveolo-capillary wall. Also seen are fluid in the basement membrane, platelets in the capillaries, and alveolar fluid and debris. All of these alterations occur at 1 atm exposure. However, after exposure to 450 mm Hg the changes are not as widespread nor as destructive as they are at the higher pressure.

  12. Program operational summary: Operational 90 day manned test of a regenerative life support system

    NASA Technical Reports Server (NTRS)

    Jackson, J. K.; Wamsley, J. R.; Bonura, M. S.; Seeman, J. S.

    1972-01-01

    An operational 90-day manned test of a regenerative life support system was successfully completed. This test was performed with a crew of four carefully selected and trained men in a space station simulator (SSS) which had a two gas atmosphere maintained at a total pressure of 68.9, 10 psia, and composed of oxygen at a partial pressure of 3.05 psia with nitrogen as the diluent. The test was planned to provide data on regenerative life support subsystems and on integrated system operations in a closed ecology, similar to that of a space station. All crew equipment and expendables were stored onboard at the start of the mission to eliminate the need for pass-in operations. The significant accomplishments of the test, some of the pertinent test results, some of the problem areas, and conclusions are presented.

  13. Bioregenerative Life Support Experiment for 90-days in a Closed Integrative Experimental Facility LUNAR PALACE 1

    NASA Astrophysics Data System (ADS)

    Liu, Hong

    A 90-day bioregenerative life support experiment with three-member crew was carried out in the closed integrative experimental facility, LUNAR PALACE 1 regenerating basic living necessities and disposing wastes to provide life support for crew. It was composed of higher plant module, animal module, and waste treatment module. The higher plant module included wheat, chufa, pea, carrot and green leafy vegetables, with aim to satisfy requirement of 60% plant food and 100% O2 and water for crew. The yellow mealworm was selected as animal module to provide partial animal protein for crew, and reared on plant inedible biomass. The higher plant and yellow mealworm were both cultivated and harvested in the conveyor-type manner. The partial plant inedible biomass and human feces were mixed and co- fermented in the waste treatment module for preparation of soil-like substrate by bioconversion, maintaining gas balance and increasing closure degree. Meanwhile, in the waste treatment module, the water and partial nitrogen from human urine were recovered by physical-chemical means. Circulation of O2 and water as well as food supply from crops cultivated in the LUNAR PALACE 1 were investigated and calculated, and simultaneously gas exchange, mass flow among different components and system closure degree were also analyzed, respectively. Furthermore, the system robustness with respect to internal variation was tested and evaluated by sensitivity analysis of the aggregative index consisting of key performance indicators like crop yield, gaseous equilibrium concentration, microbial community composition, biogenic elements dynamics, etc., and comprehensively evaluating the operating state, to number change of crew from 2 to 4 during the 90-day closed experiment period.

  14. A 90-day subchronic feeding study of genetically modified rice expressing Cry1Ab protein in Sprague-Dawley rats.

    PubMed

    Song, Huan; He, Xiaoyun; Zou, Shiying; Zhang, Teng; Luo, Yunbo; Huang, Kunlun; Zhu, Zhen; Xu, Wentao

    2015-04-01

    Bacillus thuringiensis (Bt) transgenic rice line (mfb-MH86) expressing a synthetic cry1Ab gene can be protected against feeding damage from Lepidopteran insects, including Sesamia inferens, Chilo suppressalis, Tryporyza incertulas and Cnaphalocrocis medinalis. Rice flour from mfb-MH86 and its near-isogenic control MH86 was separately formulated into rodent diets at concentrations of 17.5, 35 and 70 % (w/w) for a 90-day feeding test with rats, and all of the diets were nutritionally balanced. In this study, the responses of rats fed diets containing mfb-MH86 were compared to those of rats fed flour from MH86. Overall health, body weight and food consumption were comparable between groups fed diets containing mfb-MH86 and MH86. Blood samples were collected prior to sacrifice and a few significant differences (p < 0.05) were observed in haematological and biochemical parameters between rats fed genetically modified (GM) and non-GM diets. However, the values of these parameters were within the normal ranges of values for rats of this age and sex, thus not considered treatment related. In addition, upon sacrifice a large number of organs were weighed, macroscopic and histopathological examinations were performed with only minor changes to report. In conclusion, these results demonstrated that no toxic effect was observed in the conditions of the experiment, based on the different parameters assessed. GM rice mfb-MH86 is as safe and nutritious as non-GM rice.

  15. A 90-day safety study of genetically modified rice expressing rhIGF-1 protein in C57BL/6J rats.

    PubMed

    Tang, Maoxue; Xie, Tingting; Cheng, Wenke; Qian, Lili; Yang, Shulin; Yang, Daichang; Cui, Wentao; Li, Kui

    2012-06-01

    Genetically modified plants expressing disease resistance traits offer new treatment strategies for human diseases, but at the same time present a challenge in terms of food safety assessment. The present 90-day feeding study was designed to assess the safety of transgenic rice expressing the recombinant human insulin-like growth factor-1 (rhIGF-1) compared to its parental wild rice. Male and female C57BL/6J rats were given a nutritionally balanced purified diet with 20% transgenic rhIGF-1 rice or 20% parental rice for 90 days. This corresponds to a mean daily rhIGF-1 protein intake of approximately 217.6 mg/kg body weight based on the average feed consumption. In the animal study a range of biological, biochemical, clinical, microbiological and pathological parameters were examined and several significant differences were observed between groups, but none of the effects were considered to be adverse. In conclusion, no adverse or toxic effects on C57BL/6J rats were observed in the design used in this 90-day study. These results will provide valuable information for the safety assessment of genetically modified food crops.

  16. Evaluation of the toxic effects of cypermethrin inhalation on the frog heart.

    PubMed

    Coşkun, Banu; Cömelekoğlu, Ulkü; Polat, Ayşe; Kaymaz, F Figen

    2004-02-01

    Cypermethrin is widely used as an insecticide on animals and in agriculture, the home, and the garden. The effect of inhaled cypermethrin on the cardiac mechanics, electrophysiology, and ultrastructure in frogs was investigated in this study. Four groups received 100 microL of cypermethrin via inhalation for different exposure times, and one group was used as a control. Electrical and mechanical activities of the heart were recorded, and heart samples were examined at light and transmission electron microscopic levels for all groups. The atrial and ventricular contractile forces on the mechanogram, the amplitude of the P wave and the QRS complex on electrocardiogram, and the heart rate were significantly decreased in cypermethrin-inhalated frogs. The total duration of contraction was prolonged in the study groups. Ultrastructurally, dilatation in smooth endoplasmic reticulum cisterns, a decrease in the number of mitochondria, disorganization in the myofibrils of myocytes, and necrotic changes in endothelial cells were observed. These results suggest that cypermethrin has cardiotoxic effects that increase with exposure time.

  17. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine

    PubMed Central

    Hirka, Gábor; Glávits, Róbert; Palmer, Philip A.; Endres, John R.; Pasics Szakonyiné, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals. PMID:27635133

  18. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine.

    PubMed

    Clewell, Amy; Hirka, Gábor; Glávits, Róbert; Palmer, Philip A; Endres, John R; Murbach, Timothy S; Marx, Tennille; Pasics Szakonyiné, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals.

  19. Inhalation toxicity of (1→3)-β-D glucan: recent advances

    PubMed Central

    Fogelmark, Birgitta; Sjöstrand, Margareta; Williams, David; Rylander, Ragnar

    1997-01-01

    To investigate the effects of (1→3)-β-D-glucan after inhalation, animals were exposed to different forms of glucan and the number of lung lavage cells was determined 24 h after exposure. None of the different forms assayed caused any increase in cell numbers. In animals exposed to endotoxin, all types of cells were increased after 24 h. A simultaneous exposure to curdlan reduced this increase in a dose-related fashion. The results suggest that (1→3)-β-D-glucan-related acute injury to the lung is induced by mechanisms other than those induced by inflammagenic agents such as endotoxin. PMID:18472855

  20. Inhalation Toxicology. 11. The Effect of Elevated Temperature on Carbon Monoxide Toxicity

    DTIC Science & Technology

    1990-12-01

    TEMPERATURE ON CARBON MONOXIDE TOXICITY INTRODUCTION The use of the laboratory rat as an animal model for determining the toxicity of combustion gases is...response of rats during exercise. J Appl Physiol. 1968; 24:747-50. 7. Hubbard RW, Matthew WT, Linduska JD, et al. The laboratory rat as a model for

  1. Ozone Inhalation Impairs Coronary Artery Dilation via Intracellular Oxidative Stress: Evidence for Serum-Borne Factors as Drivers of Systemic Toxicity

    PubMed Central

    Paffett, Michael L.; Zychowski, Katherine E.; Sheppard, Lianne; Robertson, Sarah; Weaver, John M.; Lucas, Selita N.; Campen, Matthew J.

    2015-01-01

    Ambient ozone (O3) levels are associated with cardiovascular morbidity and mortality, but the underlying pathophysiological mechanisms driving extrapulmonary toxicity remain unclear. This study examined the coronary vascular bed of rats in terms of constrictive and dilatory responses to known agonists following a single O3 inhalation exposure. In addition, serum from exposed rats was used in ex vivo preparations to examine whether bioactivity and toxic effects of inhaled O3 could be conveyed to extrapulmonary systems via the circulation. We found that 24 h following inhalation of 1 ppm O3, isolated coronary vessels exhibited greater basal tone and constricted to a greater degree to serotonin stimulation. Vasodilation to acetylcholine (ACh) was markedly diminished in coronary arteries from O3-exposed rats, compared with filtered air-exposed controls. Dilation to ACh was restored by combined superoxide dismutase and catalase treatment, and also by NADPH oxidase inhibition. When dilute (10%) serum from exposed rats was perfused into the lumen of coronary arteries from unexposed, naïve rats, the O3-induced reduction in vasodilatory response to ACh was partially recapitulated. Furthermore, following O3 inhalation, serum exhibited a nitric oxide scavenging capacity, which may partially explain blunted ACh-mediated vasodilatory responses. Thus, bioactivity from inhalation exposures may be due to compositional changes of the circulation. These studies shed light on possible mechanisms of action that may explain O3-associated cardiac morbidity and mortality in humans. PMID:25962394

  2. Inhalation Toxicity of Ground Lunar Dust Prepared from Apollo-14 Soil

    NASA Technical Reports Server (NTRS)

    James, John T.; Lam, Chiu-wing; Scully, Robert R.; Cooper, Bonnie L.

    2011-01-01

    Within the decade one or more space-faring nations intend to return humans to the moon for more in depth exploration of the lunar surface and subsurface than was conducted during the Apollo days. The lunar surface is blanketed with fine dust, much of it in the respirable size range (<10 micron). Eventually, there is likely to be a habitable base and rovers available to reach distant targets for sample acquisition. Despite designs that could minimize the entry of dust into habitats and rovers, it is reasonable to expect lunar dust to pollute both as operations progress. Apollo astronauts were exposed briefly to dust at nuisance levels, but stays of up to 6 months on the lunar surface are envisioned. Will repeated episodic exposures to lunar dust present a health hazard to those engaged in lunar exploration? Using rats exposed to lunar dust by nose-only inhalation, we set out to investigate that question.

  3. Ethylene Oxide: Acute Four-Hour and One-Hour Inhalation Toxicity Testing in Rats

    PubMed Central

    Snellings, William M.; Nachreiner, Donald J.; Pottenger, Lynn H.

    2011-01-01

    Ethylene oxide was tested on groups of rats for either 4-hour or 1-hour inhalation exposure, followed by 14 days of observation. Groups of five Sprague-Dawley rats/sex were exposed, and clinical signs and mortality were recorded. Clinical signs noted included irregular breathing, absence of certain reflexes, and tremors. Rats that died had moderate to severe pulmonary congestion. The calculated LC50 values, reported as ppm by volume (with 95% confidence limits), were as follows. 4-hour LC50 values were 1972 (1887 to 2061) ppm for males; 1537 (1391 to 1698) ppm for females; 1741 (1655 to 1831) ppm for the combined sexes. The 1-hour LC50 values were 5748 (5276 to 6262) ppm for males; 4439 (4034 to 4884) ppm for females; 5029 (4634 to 5459) ppm for the combined sexes. PMID:21785591

  4. The importance of anatomical realism for validation of physiological models of disposition of inhaled toxicants.

    PubMed

    Kohn, M C

    1997-12-01

    The goodness of fit of three PBPK models to data for inhalation uptake of 1,3-butadiene by mice from closed chambers were compared. These models included a classical flow-limited model with blood consolidated into arterial and venous compartments, a flow-limited model with implicit blood and alveolar compartments, and a model with an actual alveolar compartment and blood distributed among compartments for arterial, venous, and capillary spaces. Using physiological and biochemical parameters from the literature, all three models reproduced observed steady-state blood butadiene concentrations. However, the first two models predicted more rapid uptake of butadiene than was observed. Assumptions such as ignoring extrahepatic metabolism or reducing the ventilation rate by 75% were required to enable these models to fit the butadiene uptake data. The behavior of the third model resembled that of the other two models when the single-pass extraction ratio of butadiene for all tissues was close to 1, but the model did reproduce observed butadiene uptake when an extraction ratio of 0.5 was used. The difference in predictions of the three models was traced to smaller computed blood:tissue gradients and tissue butadiene concentrations, hence reduced rates of metabolic clearance, when the blood is distributed. These results suggest that the common assumption of flow limitation in the disposition of an inhaled gas may not always be appropriate. Because structurally different models can reproduce the same uptake data and all these models cannot be correct, the assumptions on which these models were based must be investigated experimentally to ensure that they are physiologically realistic.

  5. Effects of 30-, 60-, and 90-Day Bed Rest on Postural Control in Men and Women

    NASA Technical Reports Server (NTRS)

    Esteves, Julie; Taylor, Laura C.; Vanya, Robert D.; Dean, S. Lance; Wood, Scott J.

    2011-01-01

    INTRODUCTION Head-down-tilt bed rest (HDT) has been used as a safe gr ound-based analog to mimic and develop countermeasures for the physiological effects of spaceflight, including decrements in postural stability. The purpose of this investigation was to characterize the effects of 30-, 60-, and 90-day bed rest on postural control in men and women. METHODS Twenty-nine subjects (18M,11F) underwent 13 days of ambula tory acclimatization and were placed in 6? HDT for 30 (n=12), 60 (n=8), or 90 (n=9) days, followed by 14 days of ambulatory recovery. Computerized dynamic posturography (CDP) was used to assess changes in sensory and motor components of postural control, and recovery after HDT. Sensory Organization Tests (SOTs) objectively evaluate one?s ability to effectively use or suppress visual, vestibular, and proprioceptive information for postural control. Stability during the SOTs was assessed using peak-to-peak sway and convergence toward stability limits to derive an equilibrium score. Motor Control Tests (MCTs) evaluate one?s ability to recover from unexpected support surface perturbations, with performance determined by center-of-pressure path length. Whole-body kinematic data were collected to determine body-sway strategy used to maintain stability during each condition. Baselines were determined pre-HDT. Recovery was tracked post-HDT on days 0, 1, 2, and 4. RESULTS Immediately after HDT, subjects showed decreased performance on most SOTs, primarily on sway-referenced support conditions, typically returning to baseline levels within 4 days. MCT performance was not significantly affected. There were no significant gender or duration differences in performance. Kinematic data revealed a tendency to use ankle strategy to maintain an upright stance during most SOT conditions. Interestingly, six subjects (2M,4F) experienced orthostatic intolerance and were unable to complete day 0 testing. CONCLUSION HDT mimics some un loading mechanisms of spaceflight and

  6. Bioaccessibility, bioavailability and toxicity of commercially relevant iron- and chromium-based particles: in vitro studies with an inhalation perspective

    PubMed Central

    2010-01-01

    Background Production of ferrochromium alloys (FeCr), master alloys for stainless steel manufacture, involves casting and crushing processes where particles inevitably become airborne and potentially inhaled. The aim of this study was to assess potential health hazards induced by inhalation of different well-characterized iron- and chromium-based particles, i.e. ferrochromium (FeCr), ferrosiliconchromium (FeSiCr), stainless steel (316L), iron (Fe), chromium (Cr), and chromium(III)oxide (Cr2O3), in different size fractions using in vitro methods. This was done by assessing the extent and speciation of released metals in synthetic biological medium and by analyzing particle reactivity and toxicity towards cultured human lung cells (A549). Results The amount of released metals normalized to the particle surface area increased with decreasing particle size for all alloy particles, whereas the opposite situation was valid for particles of the pure metals. These effects were evident in artificial lysosomal fluid (ALF) of pH 4.5 containing complexing agents, but not in neutral or weakly alkaline biological media. Chromium, iron and nickel were released to very low extent from all alloy particles, and from particles of Cr due to the presence of a Cr(III)-rich protective surface oxide. Released elements were neither proportional to the bulk nor to the surface composition after the investigated 168 hours of exposure. Due to a surface oxide with less protective properties, significantly more iron was released from pure iron particles compared with the alloys. Cr was predominantly released as Cr(III) from all particles investigated and was strongly complexed by organic species of ALF. Cr2O3 particles showed hemolytic activity, but none of the alloy particles did. Fine-sized particles of stainless steel caused however DNA damage, measured with the comet assay after 4 h exposure. None of the particles revealed any significant cytotoxicity in terms of cell death after 24 h

  7. Chronic cardiac toxicity after inhalation of 1,1,1-trichloroethane.

    PubMed Central

    McLeod, A A; Marjot, R; Monaghan, M J; Hugh-Jones, P; Jackson, G

    1987-01-01

    Two patients showed evidence of chronic cardiac toxicity after repeated exposure to 1,1,1-trichloroethane. In both cases there was circumstantial evidence of a deterioration after routine anaesthetic use of the related compound halothane. An adolescent boy who sniffed trichloroethane presented with multiple ventricular arrhythmias during tonsillectomy. Follow up showed mild chronic left ventricular impairment. A 54 year old man had repeated industrial exposure to trichloroethane and deteriorated from mild stable cardiac failure to end stage cardiac failure after halothane anaesthesia for herniorrhaphy. Chronic cardiac toxicity is a previously unreported feature of this type of solvent exposure. Related compounds such as halothane may have a toxic interaction after exposure to trichloroethane. Images FIG. 1 FIG. 2 PMID:3105712

  8. Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure

    PubMed Central

    Gosens, Ilse; Cassee, Flemming R.; Zanella, Michela; Manodori, Laura; Brunelli, Andrea; Costa, Anna Luisa; Bokkers, Bas G. H.; de Jong, Wim H.; Brown, David; Hristozov, Danail; Stone, Vicki

    2016-01-01

    Abstract Introduction: Increased use of nanomaterials has raised concerns about the potential for undesirable human health and environmental effects. Releases into the air may occur and, therefore, the inhalation route is of specific interest. Here we tested copper oxide nanoparticles (CuO NPs) after repeated inhalation as hazard data for this material and exposure route is currently lacking for risk assessment. Methods: Rats were exposed nose-only to a single exposure concentration and by varying the exposure time, different dose levels were obtained (C × T protocol). The dose is expressed as 6 h-concentration equivalents of 0, 0.6, 2.4, 3.3, 6.3, and 13.2 mg/m3 CuO NPs, with a primary particle size of 10 9.2–14 nm and an MMAD of 1.5 μm. Results: Twenty-four hours after a 5-d exposure, dose-dependent lung inflammation and cytotoxicity were observed. Histopathological examinations indicated alveolitis, bronchiolitis, vacuolation of the respiratory epithelium, and emphysema in the lung starting at 2.4 mg/m3. After a recovery period of 22 d, limited inflammation was still observed, but only at the highest dose of 13.2 mg/m3. The olfactory epithelium in the nose degenerated 24 h after exposure to 6.3 and 13.2 mg/m3, but this was restored after 22 d. No histopathological changes were detected in the brain, olfactory bulb, spleen, kidney and liver. Conclusion: A 5-d, 6-h/day exposure equivalent to an aerosol of agglomerated CuO NPs resulted in a dose-dependent toxicity in rats, which almost completely resolved during a 3-week post-exposure period. PMID:27132941

  9. Fate and toxic effects of inhaled ultrafine cadmium oxide particles in the rat lung.

    PubMed

    Takenaka, S; Karg, E; Kreyling, W G; Lentner, B; Schulz, H; Ziesenis, A; Schramel, P; Heyder, J

    2004-01-01

    Female Fischer 344 rats were exposed to ultrafine cadmium oxide particles, generated by spark discharging, for 6 h at a concentration of 70 microg Cd/m(3) (1 x 10(6)/cm(3)) (40 nm modal diameter). Lung morphology and quantification of Cd content/concentration by inductively coupled plasma (ICP)-mass spectrometry were performed on days 0, 1, 4, and 7 after exposure. Cd content in the lung on day 0 was 0.53 +/- 0.12 microg/lung, corresponding to 19% of the estimated total inhaled cumulative dose, and the amount remained constant throughout the study. In the liver no significant increase of Cd content was found up to 4 days. A slight but statistically significant increase was observed in the liver on day 7. We found neither exposure-related morphological changes of lungs nor inflammatory responses in lavaged cells. Another group of rats were exposed to a higher concentration of ultrafine CdO particles (550 microg Cd/m(3) for 6 h, 51 nm modal diameter). The rats were sacrificed immediately and 1 day after exposure. The lavage study performed on day 0 showed an increase in the percentage of neutrophils. Multifocal alveolar inflammation was seen histologically on day 0 and day 1. Although the Cd content in the lung was comparable between day 0 and day 1 (3.9 microg/lung), significant elevation of Cd levels in the liver and kidneys was observed on both days. Two of 4 rats examined on day 0 showed elevation of blood cadmium, indicating systemic translocation of a fraction of deposited Cd from the lung in this group. These results and comparison with reported data using fine CdO particles indicate that inhalation of ultrafine CdO particles results in efficient deposition in the rat lung. With regard to the deposition dose, adverse health effects of ultrafine CdO and fine CdO appear to be comparable. Apparent systemic translocation of Cd took place only in animals exposed to a high concentration that induced lung injury.

  10. Comparative safety testing of genetically modified foods in a 90-day rat feeding study design allowing the distinction between primary and secondary effects of the new genetic event.

    PubMed

    Knudsen, Ib; Poulsen, Morten

    2007-10-01

    This article discusses the wider experiences regarding the usefulness of the 90-day rat feeding study for the testing of whole foods from genetically modified (GM) plant based on data from a recent EU-project [Poulsen, M., Schrøder, M., Wilcks, A., Kroghsbo, S., Lindecrona, R.H., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Shu, Q., Emami, K., Taylor, M., Gatehouse, A., Engel, K.-H., Knudsen, I., 2007a. Safety testing of GM-rice expressing PHA-E lectin using a new animal test design. Food Chem. Toxicol. 45, 364-377; Poulsen, M., Kroghsbo, S., Schrøder, M., Wilcks, A., Jacobsen, H., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Shu, Q., Emami, K., Sudhakar, D., Gatehouse, A., Engel, K.-H., Knudsen, I., 2007b. A 90-day safety in Wistar rats fed genetically modified rice expressing snowdrop lectin Galanthus nivalis (GNA). Food Chem. Toxicol. 45, 350-363; Schrøder, M., Poulsen, M., Wilcks, A., Kroghsbo, S., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Emami, K., Gatehouse, A., Shu, Q., Engel, K.-H., Knudsen, I., 2007. A 90-day safety study of genetically modified rice expressing Cry1Ab protein (Bacillus thuringiensis toxin) in Wistar rats. Food Chem. Toxicol. 45, 339-349]. The overall objective of the project has been to develop and validate the scientific methodology necessary for assessing the safety of foods from genetically modified plants in accordance with the present EU regulation. The safety assessment in the project is combining the results of the 90-day rat feeding study on the GM food with and without spiking with the pure novel gene product, with the knowledge about the identity of the genetic change, the compositional data of the GM food, the results from in-vitro/ex-vivo studies as well as the results from the preceding 28-day toxicity study with the novel gene product, before the hazard characterisation is concluded. The results demonstrated the ability of the 90-day rat feeding study to detect the biological/toxicological effects of the

  11. The Acute Inhalation Toxicity in Rats from the Pyrolysis Products of Four Fluoropolymers

    NASA Technical Reports Server (NTRS)

    Carter, V. L., Jr.; Bafus, D. A.; Warrington, H. P.; Harris, E. S.

    1974-01-01

    Male Sprague-Dawley rats (225?250 g) were exposed to the thermal degradation products from four fluoropolymers. The three polymers containing vinylidene fluoride and hexafluoropropene (VF2/HFP) were pyrolyzed at 550? and 800?C, whereas polytetrafluoroethylene (PTFE) was pyrolyzed at 625 and 800?C. At the lower temperatures, the pyrolysate from the copolymer of vinylidene fluoride and hexafluoropropene (VF2/HFP) was less toxic than the pyrolysates from either the terpolymer of vinyidene fluoride, hexafluoropropene, and tetrafluoroethylene (VF2/HFP/TFE) or the copolymer of vinylidene fluoride and hexafluoropropene with ?additives? (VF2/HFP-A). However, the pyrolysates from the VF2/HFP-containing materials produced less toxic products than the pyrolysate from PTFE at 625?C. When the pyrolysis temperature was increased to 800?C, very little difference was noted between the pyrolysis toxicity for any of the VF2/HFP-containing polymers with the most toxic pyrolysate again produced by PTFE. Carbon monoxide levels were all sublethal. No correlation could be established between hydrolyzable fluoride levels and the lethality of the pyrolysates. Death following exposure occurred within 48 hr due to acute pulmonary edema and hemorrhage. Survival of this acute phase was followed by alveolar lymphocytic infiltration and peribronchial tissue proliferation.

  12. 40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... effects on the structure or functions of the respiratory system related to exposure to a chemical... the respiratory system by examining changes in the content of the lavage fluid of the lung. At 24 hrs... significant toxic effects on the respiratory organ system are produced are compared to those levels...

  13. 40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... effects on the structure or functions of the respiratory system related to exposure to a chemical... the respiratory system by examining changes in the content of the lavage fluid of the lung. At 24 hrs... significant toxic effects on the respiratory organ system are produced are compared to those levels...

  14. 40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... effects on the structure or functions of the respiratory system related to exposure to a chemical... the respiratory system by examining changes in the content of the lavage fluid of the lung. At 24 hrs... significant toxic effects on the respiratory organ system are produced are compared to those levels...

  15. 40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... effects on the structure or functions of the respiratory system related to exposure to a chemical... the respiratory system by examining changes in the content of the lavage fluid of the lung. At 24 hrs... significant toxic effects on the respiratory organ system are produced are compared to those levels...

  16. 40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... effects on the structure or functions of the respiratory system related to exposure to a chemical... the respiratory system by examining changes in the content of the lavage fluid of the lung. At 24 hrs... significant toxic effects on the respiratory organ system are produced are compared to those levels...

  17. Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX.

    PubMed

    Nambiar, Madhusoodana P; Gordon, Richard K; Rezk, Peter E; Katos, Alexander M; Wajda, Nikolai A; Moran, Theodore S; Steele, Keith E; Doctor, Bhupendra P; Sciuto, Alfred M

    2007-03-01

    To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m(3) of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure.

  18. Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX

    SciTech Connect

    Nambiar, Madhusoodana P.; Doctor, Bhupendra P.

    2007-03-15

    To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m{sup 3} of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure.

  19. A clinical pathologic study of four adult cases of acute mercury inhalation toxicity

    SciTech Connect

    Kanluen, S.; Gottlieb, C.A. )

    1991-01-01

    We report four cases of fatal mercury vapor inhalation, a rare occurrence. The mercury vapor was released at a private home, where one of the occupants was smelting silver from dental amalgam containing an unknown amount of mercury. Within 24 hours of the incident, all occupants began having shortness of breath necessitating hospital admission. The clinical courses are briefly detailed; however, all included rapid deterioration with respiratory failure. Chest roentgenograms in all four cases were consistent with adult respiratory distress syndrome. All patients were treated with dimercaprol, a mercury chelator, but all died, with survival varying from 9 to 23 days postexposure. Autopsies were performed on all four patients. The lungs in all cases were heavy, firm, and airless. Histologic examination revealed severe diffuse alveolar damage, with variable amounts of fibrosis, conforming with acute lung injury in various stages of organization. Additional postmortem findings included acute proximal renal tubular necrosis, vacuolar hepatoxicity, and a spectrum of central nervous system alterations including multifocal ischemic necrosis, gliosis, and vasculitis.

  20. Six-month low level chlorine dioxide gas inhalation toxicity study with two-week recovery period in rats

    PubMed Central

    2012-01-01

    Background Chlorine dioxide (CD) gas has a potent antimicrobial activity at extremely low concentration and may serve as a new tool for infection control occupationally as well as publicly. However, it remains unknown whether the chronic exposure of CD gas concentration effective against microbes is safe. Therefore, long-term, low concentration CD gas inhalation toxicity was studied in rats as a six-month continuous whole-body exposure followed by a two-week recovery period, so as to prove that the CD gas exposed up to 0.1 ppm (volume ratio) is judged as safe on the basis of a battery of toxicological examinations. Methods CD gas at 0.05 ppm or 0.1 ppm for 24 hours/day and 7 days/week was exposed to rats for 6 months under an unrestrained condition with free access to chow and water in a chamber so as to simulate the ordinary lifestyle in human. The control animals were exposed to air only. During the study period, the body weight as well as the food and water consumptions were recorded. After the 6-month exposure and the 2-week recovery period, animals were sacrificed and a battery of toxicological examinations, including biochemistry, hematology, necropsy, organ weights and histopathology, were performed. Results Well regulated levels of CD gas were exposed throughout the chamber over the entire study period. No CD gas-related toxicity sign was observed during the whole study period. No significant difference was observed in body weight gain, food and water consumptions, and relative organ weight. In biochemistry and hematology examinations, changes did not appear to be related to CD gas toxicity. In necropsy and histopathology, no CD gas-related toxicity was observed even in expected target respiratory organs. Conclusions CD gas up to 0.1 ppm, exceeding the level effective against microbes, exposed to whole body in rats continuously for six months was not toxic, under a condition simulating the conventional lifestyle in human. PMID:22348507

  1. Acute and Short-Term Inhalation Toxicity Study of FT Fuel

    DTIC Science & Technology

    2011-02-01

    than JP-8 in equivalent tests . In addition, micronucleus induction was tested ; FT jet fuel does not induce micronuclei, indicating that the fuel is...OECD, 1981). A separate group of rats were used as controls for assessment of micronucleus induction in order to complete the genotoxicity testing of...toxicity study in F344 rats was investigated in a short-term mutagenicity assay, the mammalian erythrocyte micronucleus (MN) test . Animals were exposed

  2. Concentrations, sources and human health risk of inhalation exposure to air toxics in Edmonton, Canada.

    PubMed

    Bari, Md Aynul; Kindzierski, Warren B

    2017-04-01

    With concern about levels of air pollutants in recent years in the Capital Region of Alberta, an investigation of ambient concentrations, sources and potential human health risk of hazardous air pollutants (HAPs) or air toxics was undertaken in the City of Edmonton over a 5-year period (2009-2013). Mean concentrations of individual HAPs in ambient air including volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs) and trace metals ranged from 0.04 to 1.73 μg/m(3), 0.01-0.54 ng/m(3), and 0.05-3.58 ng/m(3), respectively. Concentrations of benzene, naphthalene, benzo(a)pyrene (BaP), arsenic, manganese and nickel were far below respective annual Alberta Ambient Air Quality Objectives. Carcinogenic and non-carcinogenic risk of air toxics were also compared with risk levels recommended by regulatory agencies. Positive matrix factorization identified six air toxics sources with traffic as the dominant contributor to total HAPs (4.33 μg/m(3), 42%), followed by background/secondary organic aerosol (SOA) (1.92 μg/m(3), 25%), fossil fuel combustion (0.92 μg/m(3), 11%). On high particulate air pollution event days, local traffic was identified as the major contributor to total HAPs compared to background/SOA and fossil fuel combustion. Carcinogenic risk values of traffic, background/SOA and metals industry emissions were above the USEPA acceptable level (1 × 10(-6)), but below a tolerable risk (1 × 10(-4)) and Alberta benchmark (1 × 10(-5)). These findings offer useful preliminary information about current ambient air toxics levels, dominant sources and their potential risk to public health; and this information can support policy makers in the development of appropriate control strategies if required.

  3. Acute toxicity assessment of choline by inhalation, intraperitoneal and oral routes in Balb/c mice.

    PubMed

    Mehta, Amit Kumar; Arora, Naveen; Gaur, Shailendra Nath; Singh, Bhanu Pratap

    2009-08-01

    Studies suggest that choline has potential to be used as a dietary supplement and a drug for immune inflammatory diseases like asthma and rhinitis. But there are apprehensions regarding adverse effects of choline when given orally in high doses. To address this knowledge gap, toxicity assessment of choline chloride was carried out by intranasal (i.n.), oral and intraperitoneal (i.p.) routes in Balb/c mice for 28days. Body weight, food and water consumption of mice were recorded daily. Hematology and clinical chemistry were assessed to check hepatocellular functions and morphological alterations of the cells. Splenocyte counts were analysed for evaluating cellular immunity. Liver function test was performed by assaying different enzyme systems in serum such as, urea, blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Body weight, food and water consumption did not differ between mice treated with choline and the saline control group. Hematologic and biochemical variables were not affected with any increase in serum toxicity marker enzymes indicating normal liver functioning. Choline administration did not affect total cholesterol and high density lipoprotein levels as compared to their respective controls. Urea and blood urea nitrogen levels in choline treated mice were not different than controls. Creatinine level was, however, higher than control in i.p. treatment group, but other parameters were normal. In conclusion, the repeated consumption of choline chloride via i.n. and oral or i.p. routes did not cause toxicity in mice in the toxicological endpoints examined.

  4. Inhalation developmental toxicology studies: Developmental toxicity of chloroprene vapors in New Zealand white rabbits. Final report

    SciTech Connect

    Mast, T.J.; Evanoff, J.J.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1994-04-01

    Chloroprene, 2-chloro-1,3-butadiene, is a colorless liquid with a pungent ethereal odor that is primarily used as an intermediate in the manufacture of neoprene rubber, and has been used as such since about 1930. This study addressed the potential for chloroprene to cause developmental toxicity in New Zealand white rabbits following gestational exposure to 0, 10, 40, or 175 ppm chloroprene vapors, 6h/dy, 7dy/wk. Each treatment group consisted of 15 artificially inseminated females exposed on 6 through 28 days of gestation (dg). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 29 dg. Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. There were no overt signs of maternal toxicity and the change in maternal body weight over the course of the study was not affected. Exposure of pregnant rabbits to chloroprene vapors on 6-28 dg had no effect on the number of implantation, the mean percent of live pups per litter, or on the incidence of resorptions per litter. The incidence of fetal malformations was not increased by exposure to chloroprene. Results of this study indicate that gestational exposure of New Zealand white rabbits to 10, 40, or 175 ppm chloroprene did not result in observable toxicity to either the dam or the offspring.

  5. Acute, 2-week, and 13-week inhalation toxicity studies on dimethylethoxysilane vapor in Fischer 344 rats.

    PubMed

    Dodd, D E; Stuart, B O; Rothenberg, S J; Kershaw, M; Mann, P C; James, J T; Lam, C W

    1994-01-01

    Dimethylethoxysilane (DMES), a volatile liquid, is used by NASA to waterproof the heat-protective silica tiles and blankets on the Space Shuttle. Acute, 2-wk, and 13-wk inhalation exposures to DMES vapor were conducted in male and female Fischer 344 rats. In the acute study, rats were exposed to 4000, 2000, 1000, 500, or 0 (control) ppm DMES for 4 h and observed for 14 days. There were no deaths. Narcosis and ataxia were observed in rats of the two highest concentrations only. These signs disappeared within 1 h following exposure. There were no DMES-related gross or microscopic tissue lesions in rats of all exposure groups. In the 2-wk study, rats were exposed for 6 h/day, 5 days/wk to 3000, 1000, 300, 100, or 0 ppm DMES. During exposure, narcosis was observed in rats of the 3000 and 1000 ppm groups. There was a mild decrease in body weight gain in rats of the 3000 ppm group. A decrease in platelet count, an increase in bile acids, and reduced weights of the thymus, testis, and liver were observed in rats of the 3000 ppm group. Microscopically, hypospermatogenesis and spermatid giant cells were observed in the seminiferous tubules of the testes of rats exposed to 3000 ppm DMES. In the 13-wk study, rats were exposed 6 h/day, 5 days/wk to 2000, 600, 160, 40, or 0 ppm DMES. During exposure, rats of the 2000 ppm group exhibited mild narcosis and loss of startle reflex. Recovery from these central nervous system signs was rapid. Body weights were mildly decreased for rats of the 2000 ppm group. There were no exposure-related effects in hematology, serum chemistry, or urinalysis. Female rats of the 2000 ppm group had delayed estrous cycles (6 days compared to 5 days in control rats). Noteworthy organ weight changes in rats of the 2000 ppm group included decreases in thymus, liver, and testicular weights; however, pathologic lesions were observed in the testes only. Sperm motility, epididymal sperm count, and testicular spermatid count were dramatically reduced

  6. Acute, 2-week, and 13-week inhalation toxicity studies on dimethylethoxysilane vapor in Fischer 344 rats

    NASA Technical Reports Server (NTRS)

    Dodd, D. E.; Stuart, B. O.; Rothenberg, S. J.; Kershaw, M.; Mann, P. C.; James, J. T.; Lam, C. W.

    1994-01-01

    Dimethylethoxysilane (DMES), a volatile liquid, is used by NASA to waterproof the heat-protective silica tiles and blankets on the Space Shuttle. Acute, 2-wk, and 13-wk inhalation exposures to DMES vapor were conducted in male and female Fischer 344 rats. In the acute study, rats were exposed to 4000, 2000, 1000, 500, or 0 (control) ppm DMES for 4 h and observed for 14 days. There were no deaths. Narcosis and ataxia were observed in rats of the two highest concentrations only. These signs disappeared within 1 h following exposure. There were no DMES-related gross or microscopic tissue lesions in rats of all exposure groups. In the 2-wk study, rats were exposed for 6 h/day, 5 days/wk to 3000, 1000, 300, 100, or 0 ppm DMES. During exposure, narcosis was observed in rats of the 3000 and 1000 ppm groups. There was a mild decrease in body weight gain in rats of the 3000 ppm group. A decrease in platelet count, an increase in bile acids, and reduced weights of the thymus, testis, and liver were observed in rats of the 3000 ppm group. Microscopically, hypospermatogenesis and spermatid giant cells were observed in the seminiferous tubules of the testes of rats exposed to 3000 ppm DMES. In the 13-wk study, rats were exposed 6 h/day, 5 days/wk to 2000, 600, 160, 40, or 0 ppm DMES. During exposure, rats of the 2000 ppm group exhibited mild narcosis and loss of startle reflex. Recovery from these central nervous system signs was rapid. Body weights were mildly decreased for rats of the 2000 ppm group. There were no exposure-related effects in hematology, serum chemistry, or urinalysis. Female rats of the 2000 ppm group had delayed estrous cycles (6 days compared to 5 days in control rats). Noteworthy organ weight changes in rats of the 2000 ppm group included decreases in thymus, liver, and testicular weights; however, pathologic lesions were observed in the testes only. Sperm motility, epididymal sperm count, and testicular spermatid count were dramatically reduced

  7. Effects of exercise exposure on toxic interactions between inhaled oxidant and aldehyde air pollutants

    SciTech Connect

    Mautz, W.J.; Kleinman, M.T.; Phalen, R.F.; Crocker, T.T.

    1988-01-01

    Respiratory tract injury resulting from inhalation of mixtures of ozone (O3) and nitrogen dioxide (NO2) and of O3 and formaldehyde (HCHO) was studied in Sprague-Dawley rats under exposure conditions of rest and exercise. Focal inflammatory injury induced in lung parenchyma by O3 exposure was measured morphometrically and HCHO injury to the nasal respiratory epithelium was measured by cell turnover using tritium-labeled thymidine. Mixtures of O3 (0.35 or 0.6 ppm) with NO2 (respectively 0.6 or 2.5 ppm) doubled the level of lung injury produced by O3 alone in resting exposures to the higher concentrations and in exercising exposures to the lower concentrations. Formaldehyde (10 ppm) mixed with O3 (0.6 ppm) resulted in reduced lung injury compared to O3 alone in resting exposures, but exercise exposure to the mixture did not show an antagonistic interaction. Nasal epithelial injury from HCHO exposure was enhanced when O3 was present in a mixture. Mixtures of O3 and NO2 at high and low concentrations formed respectively 0.73 and 0.02 ppm nitric acid (HNO3) vapor. Chemical interactions among the oxidants, HNO3, and other reaction products (N2O5 and nitrate radical) and lung tissue may be the basis for the O3-NO2 synergism. Increased dose and dose rate associated with exercise exposure may explain the presence of synergistic interaction at lower concentrations than observed in resting exposure. No oxidation products were detected in O3-HCHO mixtures, and the antagonistic interaction observed in lung tissue during resting exposure may result from irritant breathing pattern interactions.

  8. 76 FR 54423 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List All...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-01

    ... on a Petition To List All Chimpanzees (Pan troglodytes) as Endangered AGENCY: Fish and Wildlife....S. Fish and Wildlife Service, announce a 90-day finding on a petition to list all chimpanzees (Pan... listing all chimpanzees as endangered may be warranted. Therefore, with the publication of this notice,...

  9. 75 FR 18782 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Thorne's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE INTERIOR Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Thorne's Hairstreak Butterfly as Endangered Correction In Federal...

  10. 77 FR 54548 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Eagle...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-05

    ... [Docket No. FWS-R8-ES-2012-0072: 4500030113] Endangered and Threatened Wildlife and Plants; 90-Day Finding... species to, or removing a species from, the Federal Lists of Endangered and Threatened Wildlife and Plants... had had portions of their genome deliberately spliced with genes from another species...

  11. 78 FR 57611 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List Alabama Shad as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-19

    ... 20, 2010, the Center for Biological Diversity (CBD), Alabama Rivers Alliance, Clinch Coalition... shad may be warranted. On April 28, 2011, in response to the negative 90-day finding, CBD filed a notice of intent to sue DOC and NMFS for alleged violations of the ESA in making its finding. CBD...

  12. 75 FR 41436 - Endangered and Threatened Wildlife; Notice of 90-Day Finding on a Petition to Revise Critical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-16

    ... 90-Day Finding on a Petition to Revise Critical Habitat for the Endangered Leatherback Sea Turtle... endangered leatherback sea turtle under the Endangered Species Act (ESA). We find that the petition does not... leatherback sea turtles and their habitat under our jurisdiction. FOR FURTHER INFORMATION CONTACT:...

  13. 78 FR 41716 - Hours of Service; Limited 90-Day Waiver From the 30-Minute Rest Break Requirement for the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-11

    ... beginning of this notice. Long-Range Weather Forecasts The FMCSA reviewed information from the National Oceanic and Atmospheric Administration's National Weather Service (NOAA). The NOAA posts long-range... Federal Motor Carrier Safety Administration 49 CFR Part 395 Hours of Service; Limited 90-Day Waiver...

  14. 78 FR 66675 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List Multiple Species of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-06

    ...; February 7, 1996). A species, subspecies, or DPS is ``endangered'' if it is in danger of extinction... extinction risk of concern for the species at issue. To make a 90-day finding on a petition to list a species.... Next, we evaluate whether the information indicates that the species at issue faces extinction...

  15. 76 FR 7820 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition to List the Texas Pipefish as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-11

    ... species, subspecies, or DPS is ``endangered'' if it is in danger of extinction throughout all or a... suggests an extinction risk of concern for the species at issue. To make a 90-day finding on a petition to... extinction risk that is cause for concern; this may be indicated in information expressly discussing...

  16. 76 FR 67401 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List All...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-01

    ... on a Petition To List All Chimpanzees (Pan troglodytes) as Endangered AGENCY: Fish and Wildlife... to list all chimpanzees (Pan troglodytes) as endangered under the Endangered Species Act of 1973, as... 54423) a 90-day finding on a petition to list all chimpanzees (Pan troglodytes) as endangered under...

  17. 78 FR 69376 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List 19 Species and 3...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-19

    ...We (NMFS) announce a 90-day finding on a petition to list 19 species and 3 subpopulations of sharks as threatened or endangered under the Endangered Species Act (ESA). We find that the petition presents substantial scientific or commercial information indicating that the petitioned action may be warranted for 9 species: Centrophorus harrissoni, Isogomphodon oxyrhynchus, Mustelus fasciatus,......

  18. 76 FR 55638 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Snowy...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-08

    ... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding... Kansas; the southern Texas coast into northeast Mexico; and the central Mexican plateau) (AOU 1957, pp... of plants, and any distinct population segment of any species of vertebrate fish or wildlife...

  19. 75 FR 55730 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on Petitions To Delist the Gray...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-14

    ... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding... the 1973 Act, published in May 1974 (USDI 1974). A third gray wolf subspecies, the Mexican wolf (C. l... ``any species or subspecies of fish and wildlife or plants, and any distinct vertebrate...

  20. 75 FR 46894 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Mexican...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-04

    ... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Mexican Gray Wolf as an Endangered Subspecies With Critical Habitat AGENCY... finding on two petitions to list the Mexican gray wolf (Canis lupus baileyi) (Mexican wolf) as...

  1. Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein.

    PubMed

    Conklin, Daniel J; Haberzettl, Petra; Jagatheesan, Ganapathy; Kong, Maiying; Hoyle, Gary W

    2016-08-31

    Acrolein is a highly toxic, volatile, unsaturated aldehyde generated during incomplete combustion as in tobacco smoke and indoor fires. Because the transient receptor potential ankyrin 1 (TRPA1) channel mediates tobacco smoke-induced lung injury, we assessed its role in high-level acrolein-induced toxicity in mice. Acrolein (100-275ppm, 10-30min) caused upper airway epithelial sloughing, bradypnea and oral gasping, hypothermia, cardiac depression and mortality. Male wild-type mice (WT, C57BL/6; 5-52weeks) were significantly more sensitive to high-level acrolein than age-matched, female WT mice. Both male and female TRPA1-null mice were more sensitive to acrolein-induced mortality than age- and sex-matched WT mice. Acrolein exposure increased lung weight:body weight ratios and lung albumin and decreased plasma albumin to a greater extent in TRPA1-null than in WT mice. Lung and plasma protein-acrolein adducts were not increased in acrolein-exposed TRPA1-null mice compared with WT mice. To assess TRPA1-dependent protective mechanisms, respiratory parameters were monitored by telemetry. TRPA1-null mice had a slower onset of breathing rate suppression ('respiratory braking') than WT mice suggesting TRPA1 mediates this protective response. Surprisingly, WT male mice treated either with a TRPA1 antagonist (HC030031; 200mg/kg) alone or with combined TRPA1 (100mg/kg) and TRPV1 (capsazepine, 10mg/kg) antagonists at 30min post-acrolein exposure (i.e., "real world" delay in treatment) were significantly protected from acrolein-induced mortality. These data show TRPA1 protects against high-level acrolein-induced toxicity in a sex-dependent manner. Post-exposure TRPA1 antagonism also protected against acrolein-induced mortality attesting to a complex role of TRPA1 in cardiopulmonary injury.

  2. Four-week inhalation toxicity, mutagenicity and immunotoxicity studies of Keum-Yeon-Cho (NosmoQ), tobacco substitute composition, in mice.

    PubMed

    Kim, Min-Young; Yoo, Gi-Yong; Yoo, Won-Ha; Choi, Jin-Hyuk; Bae, Mi-Ok; Kim, Jun-Sung; Kim, Hyun-Woo; Moon, Seo-Hyun; Kim, Jung-Hyun; Han, Kyu-Tae; Chae, Chan-Hee; Kim, Myung-Soo; Cho, Myung-Haing

    2003-01-01

    Safety of Keum-Yeon-Cho (NosmoQ), a tobacco substitute composition, was evaluated in terms of acute- and 4 weeks repeated-inhalation toxicity, mutagenicity, and immunotoxicity using Balb/c mice. The air inside the inhalation chamber was collected and analyzed by GC-MS. In acute inhalation toxicity test, male and female mice were exposed to 40 Keum-Yeon-Cho cigarettes. The 50% lethal concentration (LC(50)) of NosmoQ was considered to be much higher than 40 cigarettes in both sexes. In 4-week repeated inhalation toxicity test, male and female mice were exposed for 6 h/day, 5 days/week for 4 weeks to 10 and 20 cigarettes per day, while control mice were exposed to filtered air. Our data indicated that no observed adverse effect level (NOAEL) of Keum-Yeon-Cho should be over 20 cigarettes per day. Results of Salmonella typhimurium reversion assay with/without histidine moiety, in vivo chromosomal aberration and in vivo micronucleus assays using mouse bone marrow cells revealed that Keum-Yeon-Cho has no mutagenicity. Evaluation of peripheral cellular immunity of mice treated with Keum-Yeon-Cho using in vitro lymphocyte proliferation assay showed no significant difference in mean stimulation index (SI) between mice exposed to Keum-Yeon-Cho and control mice. Mean CO concentrations and total particulate matter contents of 10 and 20 cigarettes were 21.1±1.23 and 40.7±1.21 ppm (mean±S.D., n=5), and 25.7±3.09 and 59.0±4.0 mg dry weight (mean±S.D., n=5), respectively. Although at negligible concentration (less than ppb level) several polycyclic aromatic hydrocarbons (PAHs) were also detected, these results indicate that NosmoQ has no toxic effect on mice.

  3. Inhaled Steroids

    MedlinePlus

    ... Medications Long-Term Control Medications Inhaled Steroids Inhaled Steroids Make an Appointment Ask a Question Refer Patient ... more about steroids? What are some common inhaled steroids? Common inhaled steroids include: Asmanex ® (mometasone) Alvesco ® (ciclesonide) ...

  4. Toxicity of chemical components of fine particles inhaled by aged rats: effects of concentration.

    PubMed

    Kleinman, Michael T; Hyde, Dallas M; Bufalino, Charles; Basbaum, Carol; Bhalla, Deepak K; Mautz, William J

    2003-09-01

    This study tested the hypothesis that exposure to mixtures containing fine particles and ozone (O3) would cause pulmonary injury and decrements in functions of immunological cells in exposed rats (22-24 months old) in a dose-dependent manner. Rats were exposed to high and low concentrations of ammonium bisulfate and elemental carbon and to 0.2 ppm O3. Control groups were exposed to purified air or O3 alone. The biological end points measured included histopathological markers of lung injury, bronchoalveolar lung fluid proteins, and measures of the function of the lung's innate immunological defenses (macrophage antigen-directed phagocytosis and respiratory burst activity). Exposure to O3 alone at 0.2 ppm did not result in significant changes in any of the measured end points. Exposures to the particle mixtures plus O3 produced statistically significant changes consistent with adverse effects. The low-concentration mixture produced effects that were statistically significant compared to purified air but, with the exception of macrophage Fc receptor binding, exposure to the high-concentration mixture did not. The effects of the low- and high-concentration mixtures were not significantly different. The study supports previous work that indicated that particle + O3 mixtures were more toxic than O3 alone.

  5. Inhalation of mercury vapor can cause the toxic effects on rat kidney.

    PubMed

    Akgül, Nilgün; Altunkaynak, Berrin Zuhal; Altunkaynak, Muhammed Eyüp; Deniz, Ömür Gülsüm; Ünal, Deniz; Akgül, Hayati Murat

    2016-01-01

    Dental amalgam has been used in dentistry as a filling material. The filler comprises mercury (Hg). It is considered one of the most important and widespread environmental pollutants, which poses a serious potential threat for the humans and animals. However, mercury deposition affects the nervous, cardiovascular, pulmonary, gastrointestinal, and especially renal systems. In most animals' species and humans, the kidney is one of the main sites of deposition of mercury and target organ for its toxicity. In this study, the effects of mercury intake on kidney in rats were searched. For the this purpose; we used 24 adult female Wistar albino rats (200 g in weight) obtained from Experimental Research and Application Center of Atatürk University with ethical approval. Besides, they were placed into a specially designed glass cage. Along this experiment for 45 days, subjects were exposed to (1 mg/m(3)/day) mercury vapor. However, no application was used for the control subjects. At the end of the experiment, kidney samples were obtained from all subjects and processed for routine light microscopic level and stereological aspect were assessed. Finally, according to our results, mercury affects the histological features of the kidney. That means, the severe effects of mercury has been shown using stereological approach, which is one of the ideal quantitative methods in the current literature. In this study, it was detected that chronic exposure to mercury vapor may lead to renal damage and diseases in an experimental rat model.

  6. Toxicity of inhaled particulate matter on the central nervous system: neuroinflammation, neuropsychological effects and neurodegenerative disease.

    PubMed

    Wang, Yan; Xiong, Lilin; Tang, Meng

    2017-03-16

    Particulate matter (PM) combined with meteorological factors cause the haze, which brings inconvenience to people's daily life and deeply endanger people's health. Accumulating literature, to date, reported that PM are closely related to cardiopulmonary disease. Outpatient visits and admissions as a result of asthma and heart attacks gradually increase with an elevated concentration of PM. Owing to its special physicochemical property, the brain could be a potential target beyond the cardiopulmonary system. Possible routes of PM to the brain via a direct route or stimulation of pro-inflammatory cytokines have been reported in several documents concerning toxicity of engineered nanoparticles in rodents. Recent studies have demonstrated that PM have implications in oxidative stress, inflammation, dysfunction of cellular organelles, as well as the disturbance of protein homeostasis, promoting neuron loss and exaggerating the burden of central nervous system (CNS). Moreover, the smallest particles (nano-sized particles), which were involved in inflammation, reactive oxygen species (ROS), microglial activation and neuron loss, may accelerate the process of the neurodevelopmental disorder and neurodegenerative disease. Potential or other undiscovered mechanisms are not mutually exclusive but complementary aspects of each other. Epidemiology studies have shown that exposure to PM could bring about neurotoxicity and play a significant role in the etiology of CNS disease, which has been gradually corroborated by in vivo and in vitro studies. This review highlights research advances on the health effects of PM with an emphasis on neurotoxicity. With the hope of enhancing awareness in the public and calling for prevention and protective measures, it is a critical topic that requires proceeding exploration. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Visual-motor response of crewmen during a simulated 90-day space mission as measured by the critical task battery

    NASA Technical Reports Server (NTRS)

    Allen, R. W.; Jex, H. R.

    1973-01-01

    In order to test various components of a regenerative life support system and to obtain data on the physiological and psychological effects of long duration exposure to confinement in a space station atmosphere, four carefully screened young men were sealed in a space station simulator for 90 days and administered a tracking test battery. The battery included a clinical test (Critical Instability Task) designed to measure a subject's dynamic time delay, and a more conventional steady tracking task, during which dynamic response (describing functions) and performance measures were obtained. Good correlation was noted between the clinical critical instability scores and more detailed tracking parameters such as dynamic time delay and gain-crossover frequency. The levels of each parameter span the range observed with professional pilots and astronaut candidates tested previously. The chamber environment caused no significant decrement on the average crewman's dynamic response behavior, and the subjects continued to improve slightly in their tracking skills during the 90-day confinement period.

  8. 77 FR 21920 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Eastern...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list either the Eastern population or the Southern Rocky Mountain (SRM) population of the boreal toad (Anaxyrus boreas boreas) as a distinct population segment (DPS) that is endangered or threatened under the Endangered Species Act of 1973, as amended (Act), and to designate critical habitat. Based on......

  9. Acute toxic effects of nerve agent VX on respiratory dynamics and functions following microinsillation inhalation exposure in guinea pigs.

    PubMed

    Rezk, Peter E; Graham, Jacob R; Moran, Theodore S; Gordon, Richard K; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2007-03-01

    Exposure to a chemical warfare nerve agent (CWNA) leads to severe respiratory distress, respiratory failure, or death if not treated. We investigated the toxic effects of nerve agent VX on the respiratory dynamics of guinea pigs following exposure to 90.4 mug/m3 of VX or saline by microinstillation inhalation technology for 10 min. Respiratory parameters were monitored by whole-body barometric plethysmography at 4, 24, and 48 h, 7 d, 18 d, and 4 wk after VX exposure. VX-exposed animals showed a significant decrease in the respiratory frequency (RF) at 24 and 48 h of recovery (p value .0329 and .0142, respectively) compared to the saline control. The tidal volume (TV) slightly increased in VX exposed animals at 24 and significantly at 48 h (p = .02) postexposure. Minute ventilation (MV) increased slightly at 4 h but was reduced at 24 h and remained unchanged at 48 h. Animals exposed to VX also showed an increase in expiratory (Te) and relaxation time (RT) at 24 and 48 h and a small reduction in inspiratory time (Ti) at 24 h. A significant increase in end expiratory pause (EEP) was observed at 48 h after VX exposure (p = .049). The pseudo lung resistance (Penh) was significantly increased at 4 h after VX exposure and remained slightly high even at 48 h. Time-course studies reveal that most of the altered respiratory dynamics returned to normal at 7 d after VX exposure except for EEP, which was high at 7 d and returned to normal at 18 d postexposure. After 1 mo, all the monitored respiratory parameters were within normal ranges. Bronchoalveolar lavage (BAL) 1 mo after exposure showed virtually no difference in protein levels, cholinesterase levels, cell number, and cell death in the exposed and control animals. These results indicate that sublethal concentrations of VX induce changes in respiratory dynamics and functions that over time return to normal levels.

  10. Comparative short-term inhalation toxicity of five organic diketopyrrolopyrrole pigments and two inorganic iron-oxide-based pigments

    PubMed Central

    Hofmann, Thomas; Ma-Hock, Lan; Strauss, Volker; Treumann, Silke; Rey Moreno, Maria; Neubauer, Nicole; Wohlleben, Wendel; Gröters, Sibylle; Wiench, Karin; Veith, Ulrich; Teubner, Wera; van Ravenzwaay, Bennard; Landsiedel, Robert

    2016-01-01

    Abstract Diketopyrrolopyrroles (DPP) are a relatively new class of organic high-performance pigments. The present inhalation and particle characterization studies were performed to compare the effects of five DPP-based pigments (coarse and fine Pigment Red 254, coarse and fine meta-chloro DPP isomer and one form of mixed chlorinated DPP isomers) and compare it to coarse and fine inorganic Pigment Red 101. Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 h/day on 5 consecutive days. Target concentrations were 30 mg/m3 as high dose for all compounds and selected based occupational exposure limits for respirable nuisance dust. Toxicity was determined after end of exposure and after 3-week recovery using broncho-alveolar lavage fluid (BALF) and microscopic examinations of the entire respiratory tract. Mixed chlorinated DPP isomers and coarse meta-chloro DPP isomer caused marginal changes in BALF, consisting of slight increases of polymorphonuclear neutrophils, and in case of coarse meta-chloro DPP increased MCP-1 and osteopontin levels. Mixed chlorinated DPP isomers, Pigment Red 254, and meta-chloro DPP caused pigment deposits and phagocytosis by alveolar macrophages, slight hypertrophy/hyperplasia of the bronchioles and alveolar ducts, but without evidence of inflammation. In contrast, only pigment deposition and pigment phagocytosis were observed after exposure to Pigment Red 101. All pigments were tolerated well and caused only marginal effects in BALF or no effects at all. Only minor effects were seen on the lung by microscopic examination. There was no evidence of systemic inflammation based on acute-phase protein levels in blood. PMID:27387137

  11. Spontaneous and Dosing Route-related Lung Lesions in Beagle Dogs from Oral Gavage and Inhalation Toxicity Studies: Differentiation from Compound-induced Lesions.

    PubMed

    Mukaratirwa, Sydney; Garcia, Begonya; Isobe, Kaori; Petterino, Claudio; Bradley, Alys

    2016-10-01

    This study was conducted to characterize lung microscopic lesions in control beagle dogs from inhalation and oral gavage toxicity studies, to determine differences associated with the route of administration, and to discuss distinguishing features from compound-induced lung lesions. Samples from 138 control dogs from oral gavage studies and 124 control dogs from inhalation (vehicle control) studies were evaluated microscopically. There was no significant sex-related difference in the incidence of all lesions. Perivascular mononuclear cell infiltration, centriacinar mixed cell infiltration, bronchopneumonia, subpleural septal fibrosis, and alveolar macrophage accumulation were the most common lesions. Aspiration pneumonia was more common in dogs from gavage studies, suggesting reflux after gavage dosing or accidental administration of test formulation as possible causes. Centriacinar mixed cell infiltration was more common in dogs from inhalation studies, suggesting mild irritation by the vehicles used. Vascular lesions, which included pulmonary arteriopathy and smooth muscle mineralization, were observed in a few animals. Some of the spontaneous lesions are similar to lesions induced by test compounds. Compared to spontaneous lesions, compound-induced lesions tend to be multifocal or diffuse, follow a pattern of distribution (e.g., centriacinar, perivascular, and interstitial), show a dose response in the incidence and severity, and may show cell-specific toxicity.

  12. Compositional and toxicological analysis of a GM potato line with reduced α-solanine content--a 90-day feeding study in the Syrian Golden hamster.

    PubMed

    Langkilde, Søren; Schrøder, Malene; Frank, Thomas; Shepherd, Louise V T; Conner, Sean; Davies, Howard V; Meyer, Otto; Danier, Jürgen; Rychlik, Michael; Belknap, William R; McCue, Kent F; Engel, Karl-Heinz; Stewart, Derek; Knudsen, Ib; Poulsen, Morten

    2012-10-01

    Steroidal glycoalkaloids (GAs) are toxins, produced by plants of the Solanaceae family. The potato plant (Solanum tuberosum L.) and its tubers predominantly contain the two GAs α-chaconine and α-solanine. These compounds are believed to act in synergy, and the degree of toxicity may therefore depend on their ratio in the potato. To determine the influence of α-solanine: α-chaconine ratio in potatoes on toxicity, a GM potato line (SGT 9-2) with reduced α-solanine content, and the parental control line (Desirée wild-type) having a traditional α-solanine: α-chaconine ratio were (1) studied for compositional similarity by analysing for a range of potato constituents, and (2) used in a 90-day feeding trial with the Syrian Golden hamster to study differential toxicity. The animal feeding study used diets with up to 60% freeze-dried potato powder from either line. Whilst data indicated some compositional differences between the GM line and its wildtype control these did not raise concerns related to nutritional value or safety. Results of the feeding trials showed a low number of significant differences between potato lines with different α-solanine: α-chaconine ratio but none were considered to raise safety concerns with regard to human (or animal) consumption.

  13. Studies on the chronic toxicity (inhalation) of four types of refractory ceramic fiber in male Fischer 344 rats.

    PubMed

    Mast, R W; McConnell, E E; Anderson, R; Chevalier, J; Kotin, P; Bernstein, D M; Thevenaz, P; Glass, L R; Miiller, W C; Hesterberg, T W

    1995-01-01

    Abstract Refractory ceramic fibers (RCF) are man-made vitreous fibers used primarily in industrial high-temperature applications, especially for insulation of furnaces and kilns. Because of their increasing use and potential for human exposure, a chronic toxicity/carcinogenicity inhalation study was conducted in Fischer 344 (F344) rats. Five groups of 140 weanling male F344 rats were exposed via noseonly inhalation to either HEPA-filtered air (chamber controls) or 30 mg/m(3) (approximately 220 fibers/cm(3)) of three types [kaolin-based, high-purity, and aluminum zirconia silica (AZS)] of "size-selected" RCF fibers (approximately 1µ in diameter and approximately 20 um in length) and an "after-service" heat-treated (2400°F for 24 h) kaolin-based fiber for 6 h/day, 5 days/wk for 24 mo. They were then held unexposed until approximately 20% survival and then sacrificed at 30 mo. A positive control group of 80 F344 rats was exposed to 10 mg/m(3) chrysotile asbestos. Croups of 3-6 animals were sacrificed at 3, 6, 9, 12, 15, 18, and 24 mo to follow the progression of lesions and to determine fiber lung burdens. Additional groups of 3 rats were removed from exposure at 3, 6, 9, 12, and 18 mo and were held until sacrificed at 24 mo (recovery groups) for similar determinations. Lung burdens increased rapidly for all RCFs, appearing to plateau by about 12 mo. By 24 mo, lung burdens ranged from 2.6 to 9.6 × 10(5) fiberslmg of dry lung tissue for the RCFs tested. Treatment-related lesions were restricted to the lungs. To some extent all types of RCF resulted in macrophage infiltration, bronchiolization of proximal alveoli, and microgranuloma formation by 3 mo of exposure. Interstitial fibrosis was observed at 6 mo for all types of RCF, except the "after-service" fiber where fibrosis was not seen until 12 mo. The lesions progressed in severity until 12-15 mo, after which they plateaued. A minimal amount of focal pleural fibrosis was first observed at 9 mo and progressed to a

  14. Prognostic Abilities and Quality Assessment of Models for the Prediction of 90-Day Mortality in Liver Transplant Waiting List Patients

    PubMed Central

    Barthold, Marc; Kaltenborn, Alexander

    2017-01-01

    Background Model of end-stage liver disease (MELD)-score and diverse variants are widely used for prognosis on liver transplant waiting-lists. Methods 818 consecutive patients on the liver transplant waiting-list included to calculate the MELD, MESO Index, MELD-Na, UKELD, iMELD, refitMELD, refitMELD-Na, upMELD and PELD-scores. Prognostic abilities for 90-day mortality were investigated applying Receiver-operating-characteristic-curve analysis. Independent risk factors for 90-day mortality were identified with multivariable binary logistic regression modelling. Methodological quality of the underlying development studies was assessed with a systematic assessment tool. Results 74 patients (9%) died on the liver transplant waiting list within 90 days after listing. All but one scores, refitMELD-Na, had acceptable prognostic performance with areas under the ROC-curves (AUROCs)>0.700. The iMELD performed best (AUROC = 0.798). In pediatric cases, the PELD-score just failed to reach the acceptable threshold with an AUROC = 0.699. All scores reached a mean quality score of 72.3%. Highest quality scores could be achieved by the UKELD and PELD-scores. Studies specifically lack statistical validity and model evaluation. Conclusions Inferior quality assessment of prognostic models does not necessarily imply inferior prognostic abilities. The iMELD might be a more reliable tool representing urgency of transplantation than the MELD-score. PELD-score is assumedly not accurate enough to allow graft allocation decision in pediatric liver transplantation. PMID:28129338

  15. First Report of 90-Day Support of Two Calves with a Continuous-Flow Total Artificial Heart

    PubMed Central

    Karimov, Jamshid H.; Moazami, Nader; Kobayashi, Mariko; Sale, Shiva; Such, Kimberly; Byram, Nicole; Sunagawa, Gengo; Horvath, David; Gao, Shengqiang; Kuban, Barry; Golding, Leonard A.; Fukamachi, Kiyotaka

    2015-01-01

    Objective The Cleveland Clinic continuous-flow total artificial heart (CFTAH) is a compact, single-piece, valveless, pulsatile pump providing self-regulated hemodynamic output to left/right circulation. We evaluated chronic in vivo pump performance, physiologic and hemodynamic parameters, and biocompatibility of the CFTAH in a well-established calf model. Methods CFTAH pumps have been implanted in 17 calves total. Hemodynamics, pump performance, and device-related adverse events were evaluated during studies and at necropsy. Results In vivo experiments demonstrated good hemodynamic performance (pump flow, 7.3 ± 0.7 L/min; left atrial pressure [LAP], 16 ± 3 mm Hg; right atrial pressure [RAP], 17 ± 3 mm Hg; RAP-LAP difference, 1 ± 2 mm Hg; mean arterial pressure, 103 ± 7 mm Hg; arterial pulse pressure, 30 ± 11 mm Hg; pulmonary arterial pressure, 34 ± 5 mm Hg). The CFTAH has operated within design specifications and never failed. With ever-improving pump design, the implants have shown no chronic hemolysis. Three recent animals with the CFTAH recovered well, with no postoperative anticoagulation, during planned in vivo durations of 30, 90, and 90 days (last two were intended to be 90-day studies). All these longest-surviving cases showed good biocompatibility, with no thromboembolism in organs. Conclusions The current CFTAH has demonstrated reliable self-regulation of hemodynamic output and acceptable biocompatibility without anticoagulation throughout 90 days of chronic implantation in calves. Meeting these milestones is in accord with our strategy to achieve transfer of this unique technology to surgical practice, thus filling the urgent need for cardiac replacement devices as destination therapy. PMID:26173607

  16. Readmission Rate and Causes at 90-Day after Radical Cystectomy in Patients on Early Recovery after Surgery Protocol

    PubMed Central

    Altobelli, Emanuela; Buscarini, Maurizio; Gill, Harcharan S.; Skinner, Eila C.

    2017-01-01

    Background: Radical cystectomy (RC) is associated with high risk of early and late perioperative complications, and readmissions. The Enhanced Recovery After Surgery (ERAS) protocol has been applied to RC showing decreased hospital stay without increased morbidity. Objective: To evaluate the specific causes of hospital readmissions in RC patients treated before and after adoption of an ERAS protocol at our institution. Methods: We retrospectively evaluated the outcome of 207 RC patients on ERAS protocol at the Stanford University Hospital from January 2012 to December 2014. We focused on early (30-day) and late (90-day) postoperative readmission rate and causes. Results were compared with a pre-ERAS consecutive series of 177 RC patients from January 2009 to December 2011. Results: In the post-ERAS time period a total of 56 patients were readmitted, 41 within the first 30 days after surgery (20%) and 15 within the following 60 days (7%). Fever, often associated with dehydration, was the most common reason for presentation to the hospital, accounting for 57% of all readmissions. At 90 days infection accounted for 53% of readmissions. Of all the patients readmitted during the first 90 days after surgery, 32 had positive urine cultures, mostly caused by Enterococcus faecalis isolated in 18 (56%). Readmission rates did not increase since the introduction of the ERAS protocol, with an incidence of 27% in the post-ERAS group versus 30% in the pre-ERAS group. Conclusions: Despite accurate adherence to most recent perioperative antibiotic guidelines, the incidence of readmissions after RC due to infection still remains significant. PMID:28149935

  17. Readmission Rate and Causes at 90-Day after Radical Cystectomy in Patients on Early Recovery after Surgery Protocol.

    PubMed

    Altobelli, Emanuela; Buscarini, Maurizio; Gill, Harcharan S; Skinner, Eila C

    2017-01-27

    Background: Radical cystectomy (RC) is associated with high risk of early and late perioperative complications, and readmissions. The Enhanced Recovery After Surgery (ERAS) protocol has been applied to RC showing decreased hospital stay without increased morbidity. Objective: To evaluate the specific causes of hospital readmissions in RC patients treated before and after adoption of an ERAS protocol at our institution. Methods: We retrospectively evaluated the outcome of 207 RC patients on ERAS protocol at the Stanford University Hospital from January 2012 to December 2014. We focused on early (30-day) and late (90-day) postoperative readmission rate and causes. Results were compared with a pre-ERAS consecutive series of 177 RC patients from January 2009 to December 2011. Results: In the post-ERAS time period a total of 56 patients were readmitted, 41 within the first 30 days after surgery (20%) and 15 within the following 60 days (7%). Fever, often associated with dehydration, was the most common reason for presentation to the hospital, accounting for 57% of all readmissions. At 90 days infection accounted for 53% of readmissions. Of all the patients readmitted during the first 90 days after surgery, 32 had positive urine cultures, mostly caused by Enterococcus faecalis isolated in 18 (56%). Readmission rates did not increase since the introduction of the ERAS protocol, with an incidence of 27% in the post-ERAS group versus 30% in the pre-ERAS group. Conclusions: Despite accurate adherence to most recent perioperative antibiotic guidelines, the incidence of readmissions after RC due to infection still remains significant.

  18. Evolution of a 90-day model of care for bundled episodic payments for congestive heart failure in home care.

    PubMed

    Feld, April; Madden-Baer, Rose; McCorkle, Ruth

    2016-01-01

    The Centers for Medicare and Medicaid Services Innovation Center's Episode-Based Payment initiatives propose a large opportunity to reduce cost from waste and variation and stand to align hospitals, physicians, and postacute providers in the redesign of care that achieves savings and improve quality. Community-based organizations are at the forefront of this care redesign through innovative models of care aimed at bridging gaps in care coordination and reducing hospital readmissions. This article describes a community-based provider's approach to participation under the Bundled Payments for Care Improvement initiative and a 90-day model of care for congestive heart failure in home care.

  19. 13-week inhalation toxicity study (including 6- and 13-week recovery periods) with ammonium persulfate dust in albino rats.

    PubMed

    Signorin, J; Ulrich, C E; Butt, M T; D'Amato, E A

    2001-11-01

    The subchronic inhalation toxicity of ammonium persulfate was characterized using Sprague-Dawley rats (20/sex/group) at respirable dust concentrations of 0, 5.0, 10.3, and 25 mg/m(3). Whole-body exposures were conducted 6 h/day, 5 days/wk for 13 wk. Gravimetric airborne test material samples were taken daily and particle size samples were taken weekly from each exposure chamber for analysis. Ten animals/sex/group were necropsied after 13 wk of exposure, and 5 animals/sex/group were held for 6- and 13-wk recovery periods. Animals were observed for clinical signs. Effects on body weight, food consumption, clinical chemistry and hematology, ophthalmologic parameters, organ weights, gross lesions, and histopathology were evaluated. There were no exposure-related deaths during the study. Rales and increased respiration rate were noted in both males and females in the 25 mg/m(3) group, and in a few animals in the 10.3 mg/m(3) group. The incidence of these clinical signs decreased to zero during the first few weeks of the recovery period. Body weights for both males and females in the 25 mg/m(3) group were significantly depressed during most of the exposure period compared to the control group. By the end of the recovery period, body weights for the exposed animals were similar to the control group values. Lung weights were elevated in the 25 mg/m(3) group after 13 wk of exposure, but were similar to controls at 6 wk postexposure. Irritation of the trachea and bronchi/bronchiole was noted microscopically after 13 wk of exposure to 25 mg/m(3). These lesions had recovered by 6 wk postexposure. Based on the results of this study, the no-observed-adverse-effect level (NOAEL) was 10.3 mg/m(3), while the no-observed-effect level (NOEL) for exposure of rats to a dust aerosol of ammonium persulfate was 5.0 mg/m(3).

  20. The development and succession of microbial communities in 90-day Bioregenerative Life Support Experiment in the Lunar Palace 1

    NASA Astrophysics Data System (ADS)

    Sun, Yi; Liu, Hong; Fu, Yuming; Liu, Bojie; Su, Qiang; Xie, Beizhen; Qin, Youcai; Dong, Chen; Liu, Guanghui

    Lunar Palace 1, as an integrative experiment facility for permanent astrobase life-support artificial closed ecosystem, is an artificial ecosystem which consists of plant cultivation, animal breeding and waste treatment units. It has been used to carry out a 90-day bioregenerative life support experiment with three crew members. Apparently, it’s hard to prevent the growth of microorganisms in such closed ecosystem for their strong adaptive capacity. Original microorganisms in the cabin, microbes in the course of loads delivery and the autologous microorganism by crew members and animals themselves are all the main source of the interior microorganisms, which may grow and regenerate in air, water and plants. Therefore, if these microorganisms could not be effectively monitored and controlled, it may cause microbial contamination and even lead to the unsteadiness of the whole closed ecosystem. In this study, the development and succession of the microbial communities of air, water system, plant system, and key facilities surfaces in Lunar Palace 1 were continuously monitored and analyzed by using plate counting method and molecular biological method during the 90-day experiment. The results were quite useful for the controlling of internal microorganisms and the safe operation of the whole system, and could also reveal the succession rules of microorganisms in an artificial closed ecosystem.

  1. Effects of 90-day feeding of transgenic Bt rice TT51 on the reproductive system in male rats.

    PubMed

    Wang, Er Hui; Yu, Zhou; Hu, Jing; Xu, Hai Bin

    2013-12-01

    Rice is a staple food crop; however, the threat of pests leads to a serious decline in its output and quality. The CryAb/CryAc gene, encodes a synthetic fusion Bacillus thuringiensis (Bt) crystal protein, was introduced into rice MingHui63 to produce insect-resistant rice TT51. This study was undertaken to investigate potential unintended effects of TT51 on the reproductive system in male rats. Male rats were treated with diets containing 60% of either TT51 or MingHui63 by weight, nutritionally balanced to an AIN93G diet, for 90days. An additional negative control group of rats were fed with a rice-based AIN93G diet. Body weights, food intake, hematology, serum chemistry, serum hormone levels, sperm parameters and relative organ/body weights were measured, and gross as well as microscopic pathology were examined. No diet-related significant differences in the values of response variables were observed between rats that were fed with diet containing transgenic TT51, MingHui63 and the control in this 90-day feeding study. In addition, necropsy and histopathology examination indicated no treatment-related changes. The results from the present study indicated that TT51 does not appear to exert any effect on the reproductive system in male rats compared with MingHui63 or the control.

  2. Modeling potential occupational inhalation exposures and associated risks of toxic organics from chemical storage tanks used in hydraulic fracturing using AERMOD.

    PubMed

    Chen, Huan; Carter, Kimberly E

    2017-05-01

    Various toxic chemicals used in hydraulic fracturing fluids may influence the inherent health risks associated with these operations. This study investigated the possible occupational inhalation exposures and potential risks related to the volatile organic compounds (VOCs) from chemical storage tanks and flowback pits used in hydraulic fracturing. Potential risks were evaluated based on radial distances between 5 m and 180 m from the wells for 23 contaminants with known inhalation reference concentration (RfC) or inhalation unit risks (IUR). Results show that chemicals used in 12.4% of the wells posed a potential acute non-cancer risks for exposure and 0.11% of the wells with may provide chronic non-cancer risks for exposure. Chemicals used in 7.5% of the wells were associated with potential acute cancer risks for exposure. Those chemicals used in 5.8% of the wells may be linked to chronic cancer risks for exposure. While eight organic compounds were associated with acute non-cancer risks for exposure (>1), methanol the major compound in the chemical storage tanks (1.00-45.49) in 7,282 hydraulic fracturing wells. Wells with chemicals additives containing formaldehyde exhibited both acute and chronic cancer risks for exposure with IUR greater than 10(-6), suggesting formaldehyde was the dominant contributor to both types of risks for exposure in hydraulic fracturing. This study also found that due to other existing on-site emission sources of VOCs and the geographically compounded air concentrations from other surrounding wells, chemical emissions data from storage tanks and flowback pits used in this study were lower than reported concentrations from field measurements where higher occupational inhalation risks for exposure may be expected.

  3. Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain

    EPA Science Inventory

    The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute an...

  4. Training and certification program of the operating staff for a 90-day test of a regenerative life support system

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Prior to beginning a 90-day test of a regenerative life support system, a need was identified for a training and certification program to qualify an operating staff for conducting the test. The staff was responsible for operating and maintaining the test facility, monitoring and ensuring crew safety, and implementing procedures to ensure effective mission performance with good data collection and analysis. The training program was designed to ensure that each operating staff member was capable of performing his assigned function and was sufficiently cross-trained to serve at certain other positions on a contingency basis. Complicating the training program were budget and schedule limitations, and the high level of sophistication of test systems.

  5. Dietary and Food Processing for a 90-day Bioregenerative Life Support Experiment in the Lunar Palace 1

    NASA Astrophysics Data System (ADS)

    Zhao, Zhiruo; Fu, Yuming; Dong, Chen; Liu, Guanghui

    A 4-day cycle dietary menu was developed to meet the requirements of balanced diet of the crew within the 90-day closed experiment of bioregenerative life support in the Lunar Palace 1. The menu consisted of items prepared from crops and insect grown inside the system, as well as prestored food. Dairy recipe was composed of breads, vegetables, meats and soups, which provided about 2900 kcal per crew member per day. During food processing, to maximize nutrient recovery and minimize waste production, the whole wheat grains and chufa nuts were milled. Further, the carrot leaves and yellow mealworms were used as salad materials and bread ingredients, respectively. The sensory acceptability of the dishes in the menu was evaluated by flavor, texture, and appearance. Our results show that all dishes in the 4-day cycle menu were highly acceptable, which satisfies nutritional requirement of the crew members in the closed habitation.

  6. A 90-day toxicology study of meat from genetically modified sheep overexpressing TLR4 in Sprague-Dawley rats.

    PubMed

    Bai, Hai; Wang, Zhixian; Hu, Rui; Kan, Tongtong; Li, Yan; Zhang, Xiaosheng; Zhang, Jinlong; Lian, Ling; Han, Hongbing; Lian, Zhengxing

    2015-01-01

    Genetic modification offers alternative strategies to traditional animal breeding. However, the food safety of genetically modified (GM) animals has attracted increasing levels of concern. In this study, we produced GM sheep overexpressing TLR4, and the transgene-positive offsprings (F1) were confirmed using the polymerase chain reaction (PCR) and Southern blot. The expression of TLR4 was 2.5-fold compared with that of the wild-type (WT) sheep samples. During the 90-day safety study, Sprague-Dawley rats were fed with three different dietary concentrations (3.75%, 7.5%, and 15% wt/wt) of GM sheep meat, WT sheep meat or a commercial diet (CD). Blood samples from the rats were collected and analyzed for hematological and biochemical parameters, and then compared with hematological and biochemical reference ranges. Despite a few significant differences among the three groups in some parameters, all other values remained within the normal reference intervals and thus were not considered to be affected by the treatment. No adverse diet-related differences in body weights or relative organ weights were observed. Furthermore, no differences were observed in the gross necropsy findings or microscopic pathology of the rats whose diets contained the GM sheep meat compared with rats whose diets contained the WT sheep meat. Therefore, the present 90-day rat feeding study suggested that the meat of GM sheep overexpressing TLR4 had no adverse effect on Sprague-Dawley rats in comparison with WT sheep meat. These results provide valuable information regarding the safety assessment of meat derived from GM animals.

  7. Distribution, elimination, and biopersistence to 90 days of a systemically introduced 30 nm ceria-engineered nanomaterial in rats.

    PubMed

    Yokel, Robert A; Au, Tu C; MacPhail, Robert; Hardas, Sarita S; Butterfield, D Allan; Sultana, Rukhsana; Goodman, Michael; Tseng, Michael T; Dan, Mo; Haghnazar, Hamed; Unrine, Jason M; Graham, Uschi M; Wu, Peng; Grulke, Eric A

    2012-05-01

    Nanoceria is used as a catalyst in diesel fuel, as an abrasive in printed circuit manufacture, and is being pursued as an antioxidant therapeutic. Our objective is to extend previous findings showing that there were no reductions of cerium in organs of the mononuclear phagocyte (reticuloendothelial) system up to 30 days after a single nanoscale ceria administration. An ~5% aqueous dispersion of citrate-stabilized 30 nm ceria, synthesized and characterized in-house, or vehicle, was iv infused into rats terminated 1, 7, 30, or 90 days later. Cageside observations were obtained daily, body weight weekly. Daily urinary and fecal cerium outputs were quantified for 2 weeks. Nine organs were weighed and samples collected from 14 tissues/organs/systems, blood and cerebrospinal fluid for cerium determination. Histology and oxidative stress were assessed. Less than 1% of the nanoceria was excreted in the first 2 weeks, 98% in feces. Body weight gain was initially impaired. Spleen weight was significantly increased in some ceria-treated groups, associated with abnormalities. Ceria was primarily retained in the spleen, liver, and bone marrow. There was little decrease of ceria in any tissue over the 90 days. Granulomas were observed in the liver. Time-dependent oxidative stress changes were seen in the liver and spleen. Nanoscale ceria was persistently retained by organs of the mononuclear phagocyte system, associated with adverse changes. The results support concern about the long-term fate and adverse effects of inert nanoscale metal oxides that distribute throughout the body, are persistently retained, and produce adverse changes.

  8. Physico-chemical properties of a novel (-)-hydroxycitric acid extract and its effect on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological changes over a period of 90 days.

    PubMed

    Shara, Michael; Ohia, Sunny E; Schmidt, Robert E; Yasmin, Taharat; Zardetto-Smith, Andrea; Kincaid, Anthony; Bagchi, Manashi; Chatterjee, Archana; Bagchi, Debasis; Stohs, Sidney J

    2004-05-01

    Garcinia cambogia-derived (-)-hydroxycitric acid (HCA) is a popular and natural supplement for weight management. HCA is a competitive inhibitor of the enzyme ATP citrate lyase, which catalyzes the conversion of citrate and coenzyme A to oxaloacetate and acetyl coenzyme A (acetyl CoA) in the cytosol. Acetyl CoA is used in the synthesis of fatty acids, cholesterol and triglycerides, and in the synthesis of acetylcholine in the central nervous system. Studies have demonstrated the efficacy of a novel 60% calcium-potassium salt of HCA derived from Garcinia cambogia (HCA-SX, Super CitriMax) in weight management. Results have shown that HCA-SX promotes fat oxidation, enhances serotonin release and availability in the brain cortex, normalizes lipid profiles, and lowers serum leptin levels in obese subjects. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicity, as well as Ames bacterial reverse mutation studies and mouse lymphoma tests have demonstrated the safety of HCA-SX. However, no detailed long-term safety of HCA-SX or any other HCA extract has been previously assessed. We evaluated the dose- and time-dependent effects of HCA-SX in Sprague-Dawley rats on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry over a period of 90 days. Furthermore, a 90-day histopathological evaluation was conducted. The animals were treated with 0, 0.2, 2.0 and 5.0% HCA-SX of feed intake and were sacrificed on 30, 60 or 90 days of treatment. The body weight and selected organ weights were assessed and correlated as a % of body weight and brain weight at 90 days of treatment. A significant reduction in body weight was observed in treated rats as compared to control animals. An advancing age-induced marginal increase in hepatic lipid peroxidation was observed in both male and female rats, while no such difference in hepatic DNA fragmentation was observed as compared to the control

  9. Short term inhalation toxicity of a liquid aerosol of glutaraldehyde-coated CdS/Cd(OH)2 core shell quantum dots in rats.

    PubMed

    Ma-Hock, L; Farias, P M A; Hofmann, T; Andrade, A C D S; Silva, J N; Arnaud, T M S; Wohlleben, W; Strauss, V; Treumann, S; Chaves, C R; Gröters, S; Landsiedel, R; van Ravenzwaay, B

    2014-02-10

    Quantum dots exhibit extraordinary optical and mechanical properties, and the number of their applications is increasing. In order to investigate a possible effect of coating on the inhalation toxicity of previously tested non-coated CdS/Cd(OH)2 quantum dots and translocation of these very small particles from the lungs, rats were exposed to coated quantum dots or CdCl2 aerosol (since Cd(2+) was present as impurity), 6h/d for 5 consecutive days. Cd content was determined in organs and excreta after the end of exposure and three weeks thereafter. Toxicity was determined by examination of broncho-alveolar lavage fluid and microscopic evaluation of the entire respiratory tract. There was no evidence for translocation of particles from the respiratory tract. Evidence of a minimal inflammatory process was observed by examination of broncho-alveolar lavage fluid. Microscopically, minimal to mild epithelial alteration was seen in the larynx. The effects observed with coated quantum dots, non-coated quantum dots and CdCl2 were comparable, indicating that quantum dots elicited no significant effects beyond the toxicity of the Cd(2+) ion itself. Compared to other compounds with larger particle size tested at similarly low concentrations, quantum dots caused much less pronounced toxicological effects. Therefore, the present data show that small particle sizes with corresponding high surfaces are not the only factor triggering the toxic response or translocation.

  10. Report of an Expert Panel on the reanalysis by of a 90-day study conducted by Monsanto in support of the safety of a genetically modified corn variety (MON 863).

    PubMed

    Doull, J; Gaylor, D; Greim, H A; Lovell, D P; Lynch, B; Munro, I C

    2007-11-01

    MON 863, a genetically engineered corn variety that contains the gene for modified Bacillus thuringiensis Cry3Bb1 protein to protect against corn rootworm, was tested in a 90-day toxicity study as part of the process to gain regulatory approval. This study was reanalyzed by Séralini et al. who contended that the study showed possible hepatorenal effects of MON 863. An Expert Panel was convened to assess the original study results as analyzed by the Monsanto Company and the reanalysis conducted by Séralini et al. The Expert Panel concludes that the Séralini et al. reanalysis provided no evidence to indicate that MON 863 was associated with adverse effects in the 90-day rat study. In each case, statistical findings reported by both Monsanto and Séralini et al. were considered to be unrelated to treatment or of no biological or clinical importance because they failed to demonstrate a dose-response relationship, reproducibility over time, association with other relevant changes (e.g., histopathology), occurrence in both sexes, difference outside the normal range of variation, or biological plausibility with respect to cause-and-effect. The Séralini et al. reanalysis does not advance any new scientific data to indicate that MON 863 caused adverse effects in the 90-day rat study.

  11. Toxicity of inhaled isocyanate in F344/N rats and B6C3F1 mice. I. Acute exposure and recovery studies

    SciTech Connect

    Bucher, J.R.; Gupta, B.N.; Adkins, B. Jr.; Thompson, M.; Jameson, C.W.; Thigpen, J.E.; Schwetz, B.A.

    1987-06-01

    Male and female F344/N rats and B6C3F1 mice were exposed to lethal and sublethal concentrations of methyl isocyanate by inhalation. Mortality, clinical signs, body and organ weights, and changes in clinical pathology and hematology were monitored immediately after 2-hr exposures and during the ensuing 3 months. Additional studies investigated the possible involvement of cyanide in the toxicity of methyl isocyanate. Deaths of rats and mice exposed to lethal concentrations (20 to 30 ppm) began within 15-18 hr, with males more prone to early death than females. A second wave of deaths occurred after 8 to 10 days, affecting primarily female rats and mice exposed to 20 to 30 ppm of methyl isocyanate, and male and female rats exposed to 10 ppm. Most deaths occurred during the first month following the exposures and were preceded by periods of severe respiratory distress. Body weights decreased in proportion to dose early, but then weight gain resumed in survivors at control rates. The only organ with a consistent, dose-related weight change was the lung, which was heavier throughout the studies in animals exposed to high concentrations of methyl isocyanate. Blood and brain cholinesterase were not inhibited. Studies attempting to measure cyanide in the blood of methyl isocyanate-exposed rats, and attempting to affect lethality with a cyanide antidote (sodium nitrite and sodium thiosulfate) gave negative results. The findings indicate that at these doses, methyl isocyanate inhalation causes deaths and persistent pulmonary changes, but no evidence of extrapulmonary toxicity in rodents. Cyanide does not appear to be involved in methyl isocyanate toxicity.

  12. Safety assessment of genetically modified milk containing human beta-defensin-3 on rats by a 90-day feeding study.

    PubMed

    Chen, Xin; Gao, Ming-Qing; Liang, Dong; Yin, Songna; Yao, Kezhen; Zhang, Yong

    2017-02-01

    In recent years, transgenic technology has been widely applied in many fields. There is concern about the safety of genetically modified (GM) products with the increased prevalence of GM products. In order to prevent mastitis in dairy cows, our group produced transgenic cattle expressing human beta-defensin-3 (HBD3) in their mammary glands, which confers resistance to the bacteria that cause mastitis. The milk derived from these transgenic cattle thus contained HBD3. The objective of the present study was to analyze the nutritional composition of HBD3 milk and conduct a 90-day feeding study on rats. Rats were divided into 5 groups which consumed either an AIN93G diet (growth purified diet for rodents recommended by the American Institute of Nutrition) with the addition of 10% or 30% HBD3 milk, an AIN93G diet with the addition of 10% or 30% conventional milk, or an AIN93G diet alone. The results showed that there was no difference in the nutritional composition of HBD3 and conventional milk. Furthermore, body weight, food consumption, blood biochemistry, relative organ weight, and histopathology were normal in those rats that consumed diets containing HBD3. No adverse effects were observed between groups that could be attributed to varying diets or gender.

  13. An estimate of equatorial wave energy flux at 9- to 90-day periods in the Central Pacific

    NASA Technical Reports Server (NTRS)

    Eriksen, Charles C.; Richman, James G.

    1988-01-01

    Deep fluctuations in current along the equator in the Central Pacific are dominated by coherent structures which correspond closely to narrow-band propagating equatorial waves. Currents were measured roughly at 1500 and 3000 m depths at five moorings between 144 and 148 deg W from January 1981 to March 1983, as part of the Pacific Equatorial Ocean Dynamics program. In each frequency band resolved, a single complex empirical orthogonal function accounts for half to three quarters of the observed variance in either zonal or meridional current. Dispersion for equatorial first meridional Rossby and Rossby gravity waves is consistent with the observed vertical-zonal coherence structure. The observations indicate that energy flux is westward and downward in long first meridional mode Rossby waves at periods 45 days and longer, and eastward and downward in short first meridional mode Rossby waves and Rossby-gravity waves at periods 30 days and shorter. A local minimum in energy flux occurs at periods corresponding to a maximum in upper-ocean meridional current energy contributed by tropical instability waves. Total vertical flux across the 9- to 90-day period range is 2.5 kW/m.

  14. Anatomical sector analysis of load-bearing tibial bone structure during 90-day bed rest and 1-year recovery.

    PubMed

    Cervinka, Tomas; Rittweger, Jörn; Hyttinen, Jari; Felsenberg, Dieter; Sievänen, Harri

    2011-07-01

    The aim of this study was to investigate whether the bone response to long bed rest-related immobility and during subsequent recovery differed at anatomically different sectors of tibial epiphysis and diaphysis. For this study, peripheral quantitative tomographic (pQCT) scans obtained from a previous 90-day 'Long Term Bed Rest' intervention were preprocessed with a new method based on statistical approach and re-analysed sector-wise. The pQCT was performed on 25 young healthy males twice before the bed rest, after the bed rest and after 1-year follow-up. All men underwent a strict bed rest intervention, and in addition, seven of them received pamidronate treatment and nine did flywheel exercises as countermeasures against disuse-related bone loss. Clearly, 3-9% sector-specific losses in trabecular density were observed at the tibial epiphysis on average. Similarly, cortical density decreased in a sector-specific way being the largest at the anterior sector of tibial diaphysis. During recovery, the bed rest-induced bone losses were practically restored and no consistent sector-specific modulation was observed in any subgroup. It is concluded that the sector-specific analysis of bone cross-sections has potential to reveal skeletal responses to various interventions that cannot be inferred from the average analysis of the whole bone cross-section. This approach is considered also useful for evaluating the bone responses from the biomechanical point of view.

  15. Results of a 90-day safety assurance study with rats fed grain from corn rootworm-protected corn.

    PubMed

    Hammond, B; Lemen, J; Dudek, R; Ward, D; Jiang, C; Nemeth, M; Burns, J

    2006-02-01

    The results of a 90-day rat feeding study with YieldGard (YieldGard Rootworm Corn is a registered trademark of Monsanto Technology, LLC.) Rootworm corn (MON 863) grain that is protected against feeding damage caused by corn rootworm larvae are presented. Corn rootworm-protection was accomplished through the introduction of a cry3Bb1 coding sequence into the corn genome for in planta production of a modified Cry3Bb1 protein from Bacillus thuringiensis. Grain from MON 863 and its near isogenic control were separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. Additionally, six groups of rats were fed diets containing grain from different conventional (non-biotechnology-derived) reference varieties. The responses of rats fed diets containing MON 863 were compared to those of rats fed grain from conventional corn varieties. All diets were nutritionally balanced and conformed to Purina Mills, Inc. specifications for Certified LabDiet 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. Overall health, body weight gain, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 863 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 863 grain, confirming that it is as safe and nutritious as existing conventional corn varieties.

  16. Results of a 90-day safety assurance study with rats fed grain from corn borer-protected corn.

    PubMed

    Hammond, B G; Dudek, R; Lemen, J K; Nemeth, M A

    2006-07-01

    The results of a 90-day rat feeding study with grain from MON 810 corn (YieldGard Cornborer -- YieldGard Cornborer is a registered trademark of Monsanto Technology, LLC) that is protected against feeding damage from corn and stalk boring lepidopteran insects are presented. Corn borer protection was accomplished through the introduction of cry1Ab coding sequences into the corn genome for in planta production of a bioactive form of Cry1Ab protein. Grain from MON 810 and its near-isogenic control was separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. (PMI). All diets were nutritionally balanced and conformed to PMI specifications for Certified LabDiet (PMI Certified LabDiet 5002 is a registered trademark of Purina Mills, Inc.) 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. The responses of rats fed diets containing MON 810 were compared to those of rats fed grain from conventional corn varieties. Overall health, body weight, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, and gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 810 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 810 grain, confirming that it is as safe and nutritious as grain from existing commercial corn varieties.

  17. Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry

    EPA Pesticide Factsheets

    EPA's methodology for estimation of inhalation reference concentrations (RfCs) as benchmark estimates of the quantitative dose-response assessment of chronic noncancer toxicity for individual inhaled chemicals.

  18. 77 FR 43799 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Gila...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-26

    ... 2010, p. 2). The petition states that aluminum is toxic to aquatic insects and cite several papers in... of pollutants from roads and off-road vehicle trails, introduction of bacteria and excess nutrients... warranted. The petition states that aluminum is toxic to aquatic insects and cite several papers in...

  19. Toxic Hazards Research Unit annual report, 1990. Annual report No. 27 (Final), 1 Oct 89-15 Nov 90

    SciTech Connect

    Wall, H.G.; Vinegar, A.; Kinkead, E.R.

    1990-12-01

    This report presents a review of the activities of the Toxic Hazards Research Unit for the period of 1 October 1989 through 15 November 1990. Research activities focused on toxicity evaluations of aerospace and naval chemicals to include aircraft fuels and rocket fuels, hydraulic fluids, ground water contaminants, and chemical defense simulants. There was increased utilization of multidisciplinary efforts for quantitative toxicology studies and the development and validation of physiologically based pharmacokinetic models for predicting toxicity responses. The General Toxicology Laboratory conducted acute studies, toxicokinetic studies, repeated-dose studies, and subchronic inhalation studies to include a 90-day continuous inhalation study using the Thomas Domes. The development and characterization of a unique high pressure aerosol generator was a significant adjunct benefitting the study conducted in the Thomas Domes.

  20. Asthma Inhalers

    MedlinePlus

    ... an inhaler into the lungs. But CFCs are ozone-depleting substances (ODSs) that hurt the environment. Manufacturers ... inhalers, that do not rob the atmosphere of ozone. “The FDA [Food and Drug Administration] and various ...

  1. Inhalant Abuse

    MedlinePlus

    ... Who may be abusing inhalants?The most common abusers of inhalants are teenagers, especially those who are ... to your child about the dangers of trying drugs can help him or her make the right ...

  2. Dose- and time-dependent effects of a novel (-)-hydroxycitric acid extract on body weight, hepatic and testicular lipid peroxidation, DNA fragmentation and histopathological data over a period of 90 days.

    PubMed

    Shara, Michael; Ohia, Sunny E; Yasmin, Taharat; Zardetto-Smith, Andrea; Kincaid, Anthony; Bagchi, Manashi; Chatterjee, Archana; Bagchi, Debasis; Stohs, Sidney J

    2003-12-01

    (-)-Hydroxycitric acid (HCA), a natural extract from the dried fruit rind of Garcinia cambogia (family Guttiferae), is a popular supplement for weight management. The dried fruit rind has been used for centuries as a condiment in Southeastern Asia to make food more filling and satisfying. A significant number of studies highlight the efficacy of Super CitriMax (HCA-SX, a novel 60% calcium-potassium salt of HCA derived from Garcinia cambogia) in weight management. These studies also demonstrate that HCA-SX promotes fat oxidation, inhibits ATP-citrate lyase (a building block for fat synthesis), and lowers the level of leptin in obese subjects. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicity studies have demonstrated the safety of HCA-SX. However, no long-term safety of HCA-SX or any other (-)-hydroxycitric acid extract has been previously assessed. In this study, we have evaluated the dose- and time-dependent effects of HCA-SX in Sprague-Dawley rats on body weight, hepatic and testicular lipid peroxidation, DNA fragmentation, liver and testis weight, expressed as such and as a % of body weight and brain weight, and histopathological changes over a period of 90 days. The animals were treated with 0, 0.2, 2.0 and 5.0% HCA-SX as feed intake and the animals were sacrificed on 30, 60 or 90 days of treatment. The feed and water intake were assessed and correlated with the reduction in body weight. HCA-SX supplementation demonstrated a reduction in body weight in both male and female rats over a period of 90 days as compared to the corresponding control animals. An advancing age-induced marginal increase in hepatic lipid peroxidation was observed in both male and female rats as compared to the corresponding control animals. However, no such difference in hepatic DNA fragmentation and testicular lipid peroxidation and DNA fragmentation was observed. Furthermore, liver and testis weight, expressed as such and as a percentage of body

  3. Inhalation exposure methodology.

    PubMed Central

    Phalen, R F; Mannix, R C; Drew, R T

    1984-01-01

    Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and gases. The various modes of inhalation exposure (whole body, head only, nose or mouth only, etc.) are described at length, including the advantages and disadvantages inherent to each mode. Numerous literature citations are included for further reading. Among the topics briefly discussed are the selection of appropriate animal species for toxicological testing, and the types of inhalation studies performed (acute, chronic, etc.). PMID:6383799

  4. Assessment of the reproductive toxicity of inhalation exposure to ethyl tertiary butyl ether in male mice with normal, low active and inactive ALDH2.

    PubMed

    Weng, Zuquan; Ohtani, Katsumi; Suda, Megumi; Yanagiba, Yukie; Kawamoto, Toshihiro; Nakajima, Tamie; Wang, Rui-Sheng

    2014-04-01

    No data are available regarding aldehyde dehydrogenase 2 (ALDH2) polymorphisms related to the reproductive toxicity possibly caused by ethyl tertiary butyl ether (ETBE). In this study, two inhalation experiments were performed in Aldh2 knockout (KO), heterogeneous (HT) and wild type (WT) C57BL/6 male mice exposed to ETBE, and the data about general toxicity, testicular histopathology, sperm head numbers, sperm motility and sperm DNA damage were collected. The results showed that the 13-week exposure to 0, 500, 1,750 and 5,000 ppm ETBE significantly decreased sperm motility and increased levels of sperm DNA strand breaks and 8-hydroxy-deoxyguanosine in both WT and KO mice, the effects were found in 1,750 and 5,000 ppm groups of WT mice, and all of the three exposed groups of KO mice compared to the corresponding control; furthermore, ETBE also caused decrease in the relative weights of testes and epididymides, the slight atrophy of seminiferous tubules of testis and reduction in sperm numbers of KO mice exposed to ≥500 ppm. In the experiment of exposure to lower concentrations of ETBE (0, 50, 200 and 500 ppm) for 9 weeks, the remarkable effects of ETBE on sperm head numbers, sperm motility and sperm DNA damage were further observed in KO and HT mice exposed to 200 ppm ETBE, but not in WT mice. Our findings suggested that only exposure to high concentrations of ETBE might result in reproductive toxicity in mice with normal active ALDH2, while low active and inactive ALDH2 enzyme significantly enhanced the ETBE-induced reproductive toxicity in mice, even exposed to low concentrations of ETBE, mainly due to the accumulation of acetaldehyde as a primary metabolite of ETBE.

  5. Acute inhalation toxicity evaluation of a 93:7 mixture of perfluoro-2-butene and 1-bromopropane, a replacement candidate for ozone depleting substances. Interim report, July--August 1997

    SciTech Connect

    Feldmann, M.L.; Leahy, H.F.; Vinegar, A.

    1997-10-01

    The DoD requires the development of toxicity profiles for chemical substitute candidates proposed to replace ozone depleting substances such as chloro- and fluorocarbons and halons. A 93:7 mixture of perfluoro-2-butene and 1-bromopropane was identified as a possible replacement candidate for ozone-depleting fire extinguishants. An acute inhalation toxicity test utilizing male and female Fischer 344 rats was performed on this test material. No deaths occurred in any of the rats exposed to 5.3 mg/L of the 93:7 perfluoro-2-butene and 1-bromopropane mixture. Body weights of male and female rats during the subsequent 14-day observation period were unaffected by treatment. The test material did not produce acute toxicity via the inhalation route.

  6. Calf venous volume during stand-test after a 90-day bed-rest study with or without exercise countermeasure

    PubMed Central

    de Chantemèle, Eric Belin; Pascaud, Ludovic; Custaud, Marc-Antoine; Capri, Arnaud; Louisy, Francis; Ferretti, Guido; Gharib, Claude; Arbeille, Philippe

    2004-01-01

    The objectives to determine both the contribution to orthostatic intolerance (OI) of calf venous volume during a stand-test, and the effects of a combined eccentric–concentric resistance exercise countermeasure on both vein response to orthostatic test and OI, after 90-day head-down tilt bed-rest (HDT). The subjects consisted of a control group (Co-gr, n = 9) and an exercise countermeasure group (CM-gr, n = 9). Calf volume and vein cross-sectional area (CSA) were assessed by plethysmography and echography during pre- and post-HDT stand-tests. From supine to standing (post-HDT), the tibial and gastronemius vein CSA increased significantly in intolerant subjects (tibial vein, +122% from pre-HDT; gastronemius veins, +145%; P < 0.05) whereas it did not in tolerant subjects. Intolerant subjects tended to have a higher increase in calf filling volume than tolerant subjects, in both sitting and standing positions. The countermeasure did not reduce OI. Absolute calf volume decreased similarly in both groups. Tibial and gastrocnemius vein CSA at rest did not change during HDT in either group. During the post-HDT stand-test, the calf filling volume increased more in the CM-gr than in the Co-gr both in the sitting (+1.3 ± 5.1%, vs.–7.3 ± 4.3%; P < 0.05) and the standing positions (+56.1 ± 23.7%vs.+1.6 ± 9.6%; P < 0.05). The volume ejected by the muscle venous pump increased only in the CM-gr (+38.3 ± 21.8%). This study showed that intolerant subjects had a higher increase in vein CSA in the standing position and a tendency to present a higher calf filling volume in the sitting and standing positions. It also showed that a combined eccentric–concentric resistance exercise countermeasure had no effects on either post-HDT OI or on the venous parameters related to it. PMID:15331681

  7. Substance use - inhalants

    MedlinePlus

    Substance abuse - inhalants; Drug abuse - inhalants; Drug use - inhalants; Glue - inhalants ... symptoms and may include: Strong cravings for the drug Having mood swings from feeling depressed to agitated ...

  8. Significance of durability of mineral fibers for their toxicity and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of inhalation studies.

    PubMed Central

    Pott, F; Roller, M; Kamino, K; Bellmann, B

    1994-01-01

    At the same time that carcinogenicity of very thin glass fibers after intrapleural and intraperitoneal (ip) administration was demonstrated (1,2) researchers found that gypsum fibers and HCI-leached chrysotile fibers were easily soluble in the peritoneal cavity. This led to the conclusion that the chemical composition of fibers was not responsible for the carcinogenesis but that the degree of carcinogenic potency of a fiber depended on the extent to which it retained its fibrous structure. A thin glass fiber with a low biodurability did not induce tumors after ip injection of a high dose, although the ip test had been criticized for being "overly sensitive." The ip model has been the most successful for determining carcinogenicity of inorganic fibers and establishing dose-response relationships; but to determine the possibilities and limitations of this test model, very high doses of nonfibrous silicon carbide and of a slightly durable glass fiber type were injected ip in Wistar rats. No obviously acute or chronic toxic effect was observed in 90 weeks, but there was a 40% incidence of serosal tumors in the group treated with glass fibers. A pilot study on the persistence of slag fibers in the omentum of rats after ip injection showed a half-time of about 1 year. It was calculated that an ip injection of 10(9) fibers would lead to a concentration of fiber numbers in the ash of the omentum in the same range as the concentration in the lung after 2 years of inhalation exposure. The long-term inhalation study with fibers in rats has been called the "gold standard" for risk characterization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7882919

  9. Acute inhalation toxicity of carbon monoxide and hydrogen cyanide revisited: Comparison of models to disentangle the concentration × time conundrum of lethality and incapacitation.

    PubMed

    Pauluhn, Juergen

    2016-10-01

    Contemporary emergency response planning guidelines are stratified to consider the threshold for serious toxicity and/or impairment of escape, relative to the potentially lethal level above this threshold and the lower level at which individuals should not experience or develop effects more serious than mild irritation. While harmonized testing guidelines and risk assessment paradigms are available for the quantification of thresholds for lethality or establishing no adverse effect levels, the quantification of 'impairment of escape' appears to be a more elusive goal. Approaches were explored in context with CO and HCN in past experimental combustion toxicology studies to estimate the time available for escape. This point of departure (POD) was compared with the non-lethal threshold (LC01) and one third thereof from published recent acute inhalation studies in rats examining the Cxt-matrix of both CO and HCN. The findings from this analysis suggest that the rat delivers the most consistent data. However, it remains challenging yet to bridge the behavioral variables of human behavior typical of escape to any surrogate animal model. For the asphyxiant gases examined, the PODs characterizing 'impairment of escape' were difficult to distinguish from those indicative of impending death. No specific modeled carboxyhemoglobin (COHb) level could be linked to onset of incapacitation. In summary, the higher ventilation of rats (kg body weight adjusted) renders this species even more susceptible than heavy breathing humans. LCt01 × 1/3 values derived from the comprehensive Cxt matrix of rat inhalation studies are considered to be most suitable and robust to estimate the human equivalent threshold (POD) of 'impairment of escape'.

  10. Thirteen-week study of toxicity of fiber-like multi-walled carbon nanotubes with whole-body inhalation exposure in rats.

    PubMed

    Kasai, Tatsuya; Umeda, Yumi; Ohnishi, Makoto; Kondo, Hitomi; Takeuchi, Tetsuya; Aiso, Shigetoshi; Nishizawa, Tomoshi; Matsumoto, Michiharu; Fukushima, Shoji

    2015-05-01

    Cancer development due to fiber-like straight type of multi-walled carbon nanotubes (MWCNTs) has raised concerns for human safety because of its shape similar to asbestos. To set concentrations of MWCNT for a rat carcinogenicity study, we conducted a 13-week whole body inhalation study. F344 male and female rats, 6-week-old at the commencement of the study, were exposed by whole-body inhalation to MWCNT at concentrations of 0, 0.2, 1 and 5 mg/m(3) with a generation and exposure system utilizing the cyclone sieve method. Measured concentrations in the exposure chambers were 0.20 ± 0.02, 1.01 ± 0.11 and 5.02 ± 0.25 mg/m(3) for 13 weeks. The MMAD (GSD) of MWCNT were 1.4-1.6 μm (2.3-3.0), and mean width and length were 94.1-98.0 nm and 5.53-6.19 μm, respectively, for each target concentration. Lung weights were increased 1.2-fold with 1 mg/m(3) and 1.3-fold with 5 mg/m(3) in both sexes compared to the controls. In the bronchoalveolar lavage fluid (BALF) analyses, inflammatory parameters were increased concentration-dependently in both sexes from 0.2 mg/m(3). Granulomatous changes in the lung were induced at 1 and 5 mg/m(3) in females and even at 0.2 mg/m(3) in males. Focal fibrosis of the alveolar wall was observed in both sexes at 1 mg/m(3) or higher. Inflammatory infiltration in the visceral pleural and subpleural areas was induced only at 5 mg/m(3). In conclusion, we determined 0.2 mg/m(3) as the low-observed-adverse-effect level (LOAEL) for respiratory tract toxicity in the present inhalation exposure study of rats.

  11. Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A®) Following Acute Repeated Inhalation Exposure

    PubMed Central

    Roberts, Jenny R; Anderson, Stacey E; Kan, Hong; Krajnak, Kristine; Thompson, Janet A; Kenyon, Allison; Goldsmith, William T; McKinney, Walter; Frazer, David G; Jackson, Mark; Fedan, Jeffrey S

    2014-01-01

    INTRODUCTION Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. METHODS The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m3, five hours per day, over nine work days, or filtered air (control). At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. RESULTS No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following methacholine (MCh) inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM) to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP) responses to these agents; however, the baseline heart rate (HR) and HR responses to isoproterenol (ISO) were significantly elevated at one-day post exposure, with resolution

  12. FURTHER REFINEMENTS AND TESTING OF APEX3.0: EPA'S POPULATION EXPOSURE MODEL FOR CRITERIA AND AIR TOXIC INHALATION

    EPA Science Inventory

    The Air Pollutants Exposure Model (APEX(3.0)) is a PC-based model that was derived from the probabilistic NAAQS Exposure Model for carbon monoxide (pNEM/CO). APEX will be one of the tools used to estimate human population exposure for criteria and air toxic pollutants as part ...

  13. Vancomycin MIC Does Not Predict 90-Day Mortality, Readmission, or Recurrence in a Prospective Cohort of Adults with Staphylococcus aureus Bacteremia

    PubMed Central

    Clemenzi-Allen, Angelo; Gahbauer, Alice; Deck, Daniel; Imp, Brandon; Vittinghoff, Eric; Chambers, Henry F.; Doernberg, Sarah

    2016-01-01

    Staphylococcus aureus bacteremia (SAB) is a tremendous health burden. Previous studies examining the association of vancomycin MIC and outcomes in patients with SAB have been inconclusive. This study evaluated the association between vancomycin MICs and 30- or 90-day mortality in individuals with SAB. This was a prospective cohort study of adults presenting from 2008 to 2013 with a first episode of SAB. Subjects were identified by an infection surveillance system. The main predictor was vancomycin MIC by MicroScan. The primary outcomes were death at 30 and 90 days, and secondary outcomes included recurrence, readmission, or a composite of death, recurrence, and readmission at 30 and 90 days. Covariates included methicillin susceptibility, demographics, illness severity, comorbidities, infectious source, and antibiotic use. Cox proportional-hazards models with propensity score adjustment were used to estimate 30- and 90-day outcomes. Of 429 unique first episodes of SAB, 11 were excluded, leaving 418 individuals for analysis. Eighty-three (19.9%) participants had a vancomycin MIC of 2 μg/ml. In the propensity-adjusted Cox model, a vancomycin MIC of 2 μg/ml compared to <2 μg/ml was not associated with a greater hazard of mortality or composite outcome of mortality, readmission, and recurrence at either 30 days (hazard ratios [HRs] of 0.86 [95% confidence interval {CI}, 0.41, 1.80] [P = 0.70] and 0.94 [95% CI, 0.55, 1.58] [P = 0.80], respectively) or 90 days (HRs of 0.91 [95% CI, 0.49, 1.69] [P = 0.77] and 0.69 [95% CI, 0.46, 1.04] [P = 0.08], respectively) after SAB diagnosis. In a prospective cohort of patients with SAB, vancomycin MIC was not associated with 30- or 90-day mortality or a composite of mortality, disease recurrence, or hospital readmission. PMID:27324762

  14. The chronic toxicity and oncogenicity of inhaled technical-grade 1,3-dichloropropene in rats and mice.

    PubMed

    Lomax, L G; Stott, W T; Johnson, K A; Calhoun, L L; Yano, B L; Quast, J F

    1989-04-01

    Male and female Fischer 344 rats and B6C3F1 mice were exposed by inhalation to target concentrations of 0, 5, 20, or 60 ppm (0, 22.7, 90.8, or 272 mg/m3) technical-grade 1,3-dichloropropene (DCPT) 6 hr/day, 5 days/week, for up to 2 years. Ancillary groups of rats and mice were exposed for 6- and 12-month periods. Significant treatment-related nonneoplastic changes following exposure for 2 years were morphological alterations in the nasal tissues of rats exposed to 60 ppm and mice exposed to 20 or 60 ppm DCPT. In addition, mice exposed to 20 or 60 ppm had hyperplasia of the transitional epithelium lining the urinary bladder. Survival of male and female rats and mice exposed to DCPT was similar to that of the corresponding controls. No statistically increased tumor incidence was observed in treated rats. The only neoplastic response observed in mice was an increased incidence of benign lung tumors (bronchioloalveolar adenomas) in male mice exposed to 60 ppm DCPT (22/50 versus 9/50 in controls).

  15. Inhaled matters of the heart

    PubMed Central

    Zaky, Ahmed; Ahmad, Aftab; Dell’Italia, Louis J; Jahromi, Leila; Reisenberg, Lee Ann; Matalon, Sadis; Ahmad, Shama

    2015-01-01

    Inhalations of atmospheric pollutants, especially particulate matters, are known to cause severe cardiac effects and to exacerbate preexisting heart disease. Heart failure is an important sequellae of gaseous inhalation such as that of carbon monoxide. Similarly, other gases such as sulphur dioxide are known to cause detrimental cardiovascular events. However, mechanisms of these cardiac toxicities are so far unknown. Increased susceptibility of the heart to oxidative stress may play a role. Low levels of antioxidants in the heart as compared to other organs and high levels of reactive oxygen species produced due to the high energetic demand and metabolic rate in cardiac muscle are important in rendering this susceptibility. Acute inhalation of high concentrations of halogen gases is often fatal. Severe respiratory injury and distress occurs upon inhalation of halogens gases, such as chlorine and bromine; however, studies on their cardiac effects are scant. We have demonstrated that inhalation of high concentrations of halogen gases cause significant cardiac injury, dysfunction, and failure that can be critical in causing mortalities following exposures. Our studies also demonstrated that cardiac dysfunction occurs as a result of a direct insult independent of coexisting hypoxia, since it is not fully reversed by oxygen supplementation. Therefore, studies on offsite organ effects of inhaled toxic gases can impact development of treatment strategies upon accidental or deliberate exposures to these agents. Here we summarize the knowledge of cardiovascular effects of common inhaled toxic gases with the intent to highlight the importance of consideration of cardiac symptoms while treating the victims. PMID:26665179

  16. A Standard Reference Material for Calibration of the Cup Furnace Smoke Toxicity Method for Assessing the Acute Inhalation Toxicity of Combustion Products.

    PubMed

    Levin, Barbara C; Paabo, Maya; Schiller, Susannah B

    1991-01-01

    A standard reference material (SRM 1048) has been developed for use with the cup furnace smoke toxicity method. This SRM is to be used to calibrate the apparatus and to enable the user to have confidence that the method is being conducted in a correct manner and that the equipment is functioning properly. The toxicological results from this SRM should not be used to compare with those of other materials (i.e., to determine if the combustion products of a test material are more or less toxic than those from this SRM). SRM 1048 is an acrylonitrile-butadiene-styrene (ABS) and is the same as SRM 1007B which is used for calibrating the flaming mode of the Smoke Density Chamber test method (ASTM E-662 and NFPA 258). For the purposes of calibrating the cup furnace smoke toxicity method, LC50 and N-Gas values plus their respective 95% confidence limits have been determined and certified for two combustion modes (flaming and nonflaming) and two observation periods (for the 30 min exposure only and for the 30 min exposure plus a 14 d post-exposure period). The certified LC50 values plus 95% confidence intervals (in g/m(3)) are 27 ± 3 (30 min, flaming); 25 ± 3 (30 min+ 14 d, flaming); 58 ± 15 (30 min, nonflaming); and 53 + 12 (30 min+ 14 d, nonflaming). The certified N-Gas values plus 95% confidence intervals are 1.4 ± 0.2 (30 min, flaming); 1.5 ± 0.2 (30 min+ 14 d, flaming); 1.2 ± 0.2 (30 min, nonflaming); and 1.4 ± 0.2 (30 min+ 14 d, nonflaming). It is recommended that this SRM be used with the N-Gas approach to calibrate the cup furnace smoke toxicity method rather than to determine the complete LC50 values. The N-Gas approach has the advantage of providing information on the gases responsible for the lethalities as well as the toxic potency of the smoke. In addition, the N-Gas approach reduces the number of experimental animals, the time necessary to complete the calibration, and the expense.

  17. 7 CFR Appendix B to Subpart C of... - FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due B Appendix B to Subpart C of Part 766 Agriculture Regulations of the... LOAN SERVICING-SPECIAL Loan Servicing Programs Pt. 766, Subpt. C, App. B Appendix B to Subpart C...

  18. 7 CFR Appendix B to Subpart C of... - FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due B Appendix B to Subpart C of Part 766 Agriculture Regulations of the... LOAN SERVICING-SPECIAL Loan Servicing Programs Pt. 766, Subpt. C, App. B Appendix B to Subpart C...

  19. A CHRONIC INHALATION STUDY OF METHYL BROMIDE TOXICITY IN B6C3F1 MICE. (FINAL REPORT TO THE NATIONAL TOXICOLOGY PROGRAM)

    SciTech Connect

    HABER, S.B.

    1987-06-26

    This report provides a detailed account of a two year chronic inhalation study of methyl bromide toxicity in B6C3Fl mice conducted for the National Toxicology Program. Mice were randomized into three dose groups (10, 33 and 100 ppm methyl bromide) and one control group (0 ppm) per sex and exposed 5 days/week, 6 hours/day, for a total of 103 weeks. Endpoints included body weight; clinical signs and mortality, and at 6, 15 and 24 months of exposure, animals were sacrificed for organ weights, hematology and histopathology. In addition, a subgroup of animals in each dosage group was monitored for neurobehavioral and neuropathological changes. After only 20 weeks of exposure, 48% of the males and 12% of the females in the 100 ppm group had died. Exposures were terminated in that group and the surviving mice were observed for the duration of the study. Exposure of B6C3Fl mice to methyl bromide, even for only 20 weeks, produced significant changes in growth rate, mortality, organ weights and neurobehavioral functioning. These changes occurred in both males and females, but were more pronounced in males.

  20. Acute Inhalation Injury

    PubMed Central

    Gorguner, Metin; Akgun, Metin

    2010-01-01

    Inhaled substances may cause injury in pulmonary epithelium at various levels of respiratory tract, leading from simple symptoms to severe disease. Acute inhalation injury (AII) is not uncommon condition. There are certain high risk groups but AII may occur at various places including home or workplace. Environmental exposure is also possible. In addition to individual susceptibility, the characteristics of inhaled substances such as water solubility, size of substances and chemical properties may affect disease severity as well as its location. Although AII cases may recover in a few days but AII may cause long-term complications, even death. We aimed to discuss the effects of short-term exposures (minutes to hours) to toxic substances on the lungs. PMID:25610115

  1. Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement.

    PubMed

    Yuan, Yanfang; Xu, Wentao; He, Xiaoyun; Liu, Haiyan; Cao, Sishuo; Qi, Xiaozhe; Huang, Kunlun; Luo, Yunbo

    2013-01-01

    Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora composition, intestinal permeability, epithelial structure, fecal enzymes, bacterial activity, and intestinal immunity. Significant differences were found between rice-fed groups and AIN93G-fed control groups in several parameters, whereas no differences were observed between genetically modified and non-genetically modified groups. No adverse effects were found on GI health resulting from genetically modified T2A-1 rice. In conclusion, this study may offer a systematic safety assessment model for GM material with respect to the effects on GI health.

  2. Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement

    PubMed Central

    Yuan, Yanfang; Xu, Wentao; He, Xiaoyun; Liu, Haiyan; Cao, Sishuo; Qi, Xiaozhe; Huang, Kunlun; Luo, Yunbo

    2013-01-01

    Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora composition, intestinal permeability, epithelial structure, fecal enzymes, bacterial activity, and intestinal immunity. Significant differences were found between rice-fed groups and AIN93G-fed control groups in several parameters, whereas no differences were observed between genetically modified and non-genetically modified groups. No adverse effects were found on GI health resulting from genetically modified T2A-1 rice. In conclusion, this study may offer a systematic safety assessment model for GM material with respect to the effects on GI health. PMID:23752350

  3. Evaluation of the Toxic Effects of a 90-Day Continuous Exposure of Rats to Water-In-Oil Hydraulic Fluid Emulsion.

    DTIC Science & Technology

    1991-09-01

    not request copies of this report from the Harry G. Armstrong Aerospace Medical Research Laboratory. Additional copies may be purchased from: National...evaluate ite poter , t! t-cs from a 9C-aay continuous exposure of water-in-oil hydraulic fluid aeroso; to rats in Thomas Dome innalation chambers An air... Harry G Armstrong Aerospace Medical Research Laboratory, Wright-Patterson Air Force Base, OH Kimmel, E.C. and H.F. Leahy. 1991 A High Pressure

  4. IN VIVO EVALUATION OF THE SEALING ABILITY OF TWO ENDODONTIC SEALERS IN ROOT CANALS EXPOSED TO THE ORAL ENVIRONMENT FOR 45 AND 90 DAYS

    PubMed Central

    Kopper, Patrícia Maria Poli; Vanni, José Roberto; Della Bona, Álvaro; de Figueiredo, José Antônio Poli; Porto, Sérgio

    2006-01-01

    This in vivo study evaluated the sealing ability of a resin-based sealer (AH Plus) and a zinc oxide-eugenol sealer (Endofill) in dogs' teeth, exposed to the oral environment for 45 and 90 days. Forty eight lower incisors from 8 dogs were endodonticaly treated. A stratified randomization determined the sealer use in each root canal. All canals were filled using the lateral condensation technique. The excess filling material at the cervical portion of the root canal was sectioned, leaving a 10-mm obturation length inside the canal. Teeth were provisionally sealed with glass ionomer cement for 24 h and the canals were exposed to the oral environment for either 45 or 90 days. Therefore, the experimental groups were as follows: A45- AH Plus for 45 days; A90- AH Plus for 90 days; E45- Endofill for 45 days; and E90- Endofill for 90 days (n=12). After the experimental period, the dogs were killed and the lower jaw was removed. The incisors were extracted and the roots were covered with two coats of nail varnish. The teeth were immersed in India ink for 96 h and submitted to diaphanization. Dye leakage (in mm) was measured using stereomicroscopy (10x magnification). The results were statistically analyzed using two-way ANOVA and Tukey test for multiple comparisons (á = 0.05). Group E90 (2.03±0.94) showed significantly higher mean leakage value than all other groups (p<0.001). None of the sealers, in both study conditions, were able to prevent dye leakage. PMID:19089029

  5. Vitamin D deficiency at admission is not associated with 90-day mortality in patients with severe sepsis or septic shock: Observational FINNAKI cohort study.

    PubMed

    Ala-Kokko, Tero I; Mutt, Shivaprakash J; Nisula, Sara; Koskenkari, Juha; Liisanantti, Janne; Ohtonen, Pasi; Poukkanen, Meri; Laurila, Jouko J; Pettilä, Ville; Herzig, Karl-Heinz

    2016-01-01

    Introduction Low levels of vitamin D have been associated with increased mortality in patients that are critically ill. This study explored whether vitamin D levels were associated with 90-day mortality in severe sepsis or septic shock. Methods Plasma vitamin D levels were measured on admission to the intensive care unit (ICU) in a prospective multicentre observational study. Results 610 patients with severe sepsis were included; of these, 178 (29%) had septic shock. Vitamin D deficiency (<50 nmol/L) was present in 333 (55%) patients. The 90-day mortality did not differ among patients with or without vitamin D deficiency (28.3% vs. 28.5%, p = 0.789). Diabetes was more common among patients deficient compared to those not deficient in vitamin D (30% vs. 18%, p < 0.001). Hospital-acquired infections at admission were more prevalent in patients with a vitamin D deficiency (31% vs. 16%, p < 0.001). A multivariable adjusted Cox regression model showed that low vitamin D levels could not predict 90-day mortality (<50 nmol/L: hazard ratio (HR) 0.99 (95% CI: 0.72-1.36), p > 0.9; and <25 nmol/L: HR 0.44 (95% CI: 0.22-0.87), p = 0.018). Conclusions Vitamin D deficiency detected upon ICU admission was not associated with 90-day mortality in patients with severe sepsis or septic shock. Key messages In severe sepsis and septic shock, a vitamin D deficiency upon ICU admission was not associated with increased mortality. Compared to patients with sufficient vitamin D, patients with deficient vitamin D more frequently exhibited diabetes, elevated C-reactive protein levels, and hospital-acquired infections upon ICU admission, and they more frequently developed acute kidney injury.

  6. Influence of CO2 change during 90-day experiment on growth characteristics and photosynthetic activity in vegetables grown in Lunar Palace 1

    NASA Astrophysics Data System (ADS)

    Shao, Lingzhi; Liu, Hong; Wang, Minjuan; Fu, Yuming; Dong, Chen; Liu, Guanghui

    To establish bioregenerative life support system (BLSS) on lunar or Mars bases in the future, it is necessary to firstly conduct manned simulation experiments on the ground. For this purpose, Lunar palace 1 as an integrative experimental facility for permanent astrobase life support artificial closed ecosystem was set up, and 90-day experiment was carried out in this system. Vegtables as one of the important plant units, provide various nutrient content for crews in the system, such as vitamin, antioxidants and so on. However, it is not clear yet that how the CO _{2} change during 90-day experiment to affect on growth characteristics and photosynthetic activity in vegtables grown in the system. In this study, red lettuce, red rape, romaine lettuce, and bibb lettuce grown in the system were chosen as the subject investigated. Growth, expressed as dry weight, length of shoot and root, leaf area, was mearsured, and photosynthesis,expressed as net photosynthetic rate, intercellular CO _{2} concentration, chlorophyll contents and fluorescence was analyzed to detemind influence of CO _{2} change during 90-day experiment on growth in vegtables grown in the system.

  7. A 90-day safety study in Sprague-Dawley rats fed milk powder containing recombinant human lactoferrin (rhLF) derived from transgenic cloned cattle.

    PubMed

    Zhou, Cui; Wang, Jian Wu; Huang, Kun Lun; He, XiaoYun; Chen, Xiu Ping; Sun, Hong; Yu, Tian; Che, Hui Lian

    2011-10-01

    Transgenic cloned animals expressing beneficial human nutritional traits offer a new strategy for large-scale production of some kinds of functional substances. In some cases, the required safety testing for genetically modified (GM) foods do not seem appropriate for human food safety, though regulations do not seem to provide alternatives. A 90-day rat feeding study is the core study for the safety assessment of GM foods. The test material in this 90-day study was prepared nonfat milk powder containing recombinant human lactoferrin (rhLF), which was expressed in transgenic cloned cattle. Groups of 10 male and female Sprague-Dawley rats were given a nutritionally balanced purified diet containing 7.5, 15, or 30% transgenic or conventional milk powder for 90 days. A commercial AIN93G diet was used as an additional control group. Clinical, biological, and pathological parameters were compared between groups. The only significant effect of treatment was higher mean ferritin and Fe(+) concentrations for both male and female rats fed the transgenic milk powder diets, as compared to rats fed nontransgenic milk diets or the commercial diet. The results of the present study are consistent with previous research, which indicates that milk powder containing rhLF derived from healthy transgenic cloned cattle is as safe as conventional milk powder.

  8. Reduced toxicological activity of cigarette smoke by the addition of ammonia magnesium phosphate to the paper of an electrically heated cigarette: subchronic inhalation toxicology.

    PubMed

    Moennikes, O; Vanscheeuwijck, P M; Friedrichs, B; Anskeit, E; Patskan, G J

    2008-05-01

    Cigarette smoke is a complex chemical mixture that causes a variety of diseases, such as lung cancer. With the electrically heated cigarette smoking system (EHCSS), temperatures are applied to the tobacco below those found in conventional cigarettes, resulting in less combustion, reduced yields of some smoke constituents, and decreased activity in some standard toxicological tests. The first generation of electrically heated cigarettes (EHC) also resulted in increased formaldehyde yields; therefore, a second generation of EHC was developed with ammonium magnesium phosphate (AMP) in the cigarette paper in part to address this increase. The toxicological activity of mainstream smoke from these two generations of EHC and of a conventional reference cigarette was investigated in two studies in rats: a standard 90-day inhalation toxicity study and a 35-day inhalation study focusing on lung inflammation. Many of the typical smoke exposure-related changes were found to be less pronounced after exposure to smoke from the second-generation EHC with AMP than to smoke from the first-generation EHC or the conventional reference cigarette, when compared on a particulate matter or nicotine basis. Differences between the EHC without AMP and the conventional reference cigarette were not as prominent. Overall, AMP incorporated in the EHC cigarette paper reduced the inhalation toxicity of the EHCSS more than expected based on the observed reduction in aldehyde yields.

  9. Ciclesonide Oral Inhalation

    MedlinePlus

    ... ciclesonide inhaler while you are near an open flame or a heat source. The inhaler may explode ... inhaler near a heat source or an open flame. Protect the inhaler from freezing and direct sunlight. ...

  10. Fluticasone Oral Inhalation

    MedlinePlus

    ... aerosol inhaler while you are near an open flame or a heat source. The inhaler may explode ... inhaler near a heat source or an open flame. Protect the inhaler from freezing and direct sunlight. ...

  11. Flunisolide Oral Inhalation

    MedlinePlus

    ... flunisolide inhaler while you are near an open flame or a heat source. The inhaler may explode ... inhaler near a heat source or an open flame. Protect the inhaler from freezing and direct sunlight. ...

  12. Inhalation Toxicology Research Institute annual report, October 1, 1993--September 30, 1994

    SciTech Connect

    Belinsky, S. A.; Hoover, M. D.; Bradley, P. L.

    1994-11-01

    This document from the Inhalation Toxicology Research Institute includes annual reports in the following general areas: (I) Aerosol Technology and Characterization of Airborne Materials; (II) Deposition, transport, and clearance of inhaled Toxicants; (III) Metabolism and Markers of Inhaled Toxicants; (IV) Carcinogenic Responses to Toxicants; (V) Mechanisms of carcinogenic response to Toxicants; (VI) Non carcinogenic responses to inhaled toxicants; (VII) Mechanisms of noncarcinogenic Responses to Inhaled Toxicants; (VIII) The application of Mathematical Modeling to Risk Estimates. 9 appendices are also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

  13. MELD-Na as a prognostic indicator of 30- and 90-day mortality in patients with end-stage liver disease after creation of transjugular intrahepatic portosystemic shunt.

    PubMed

    Ahmed, Rezwan; Santhanam, Prasanna; Rayyan, Yaser

    2015-10-01

    Previous studies have shown that the Model for End-Stage Liver Disease (MELD) score is superior to other liver disease scoring systems to establish optimal candidates for transjugular intrahepatic portosystemic shunt (TIPS) procedure and liver transplantation. Our aim was to compare MELD-Na score with MELD score as a predictor of 30-day as well as 90-day mortality for individuals with end-stage liver disease (ESLD) after creation of TIPS. We performed a chart review on cirrhotic patients who underwent TIPS procedure and documented presence and severity of ascites and hepatic encephalopathy, patient laboratory values, and results from TIPS procedures. We compared continuous variables by Student's t-test for independent samples and categorical variables by χ-test(s). In non-normal distributions, a nonparametric test was used. We performed a logistic regression to determine the effects of several variables and analyzed variable predictors of likelihood of death within 30 and 90 days of TIPS procedure. Of the six predictor variables, only MELD-Na score was a statistically significant predictor of 30- and 90-day mortality following TIPS procedure for ESLD (P=0.028). For each one point increase in MELD-Na score, the odds of death increased by 1.15 times [95% confidence interval (1.02-1.30), P=0.28]. Since hyponatremia may be associated with poor prognostic features of overall health, its incorporation into the MELD scoring system to predict mortality in ESLD after creation of TIPS serves a useful purpose. Our single-center experience suggests that the MELD-Na score is the most effective predictor of survival after TIPS creation.

  14. Predictors of 30-Day Mortality and 90-Day Functional Recovery after Primary Intracerebral Hemorrhage : Hospital Based Multivariate Analysis in 585 Patients

    PubMed Central

    2009-01-01

    Objective The purpose of this study was to identify independent predictors of mortality and functional recovery in patients with primary intracerebral hemorrhage (PICH) and to improve functional outcome in these patients. Methods Data were collected retrospectively on 585 patients with supratentorial PICH admitted to the Stroke Unit at our hospital between 1st January 2004 and the 31st July 2008. Using multivariate logistic regression analysis, the associations between all selected variables and 30-day mortality and 90-day functional recoveries after PICH was evaluated. Results Ninety-day functional recovery was achieved in 29.1% of the 585 patients and 30-day mortality in 15.9%. Age (OR=7.384, p=0.000), limb weakness (OR=6.927, p=0.000), and hematoma volume (OR=5.293, p=0.000) were found to be powerful predictors of 90-day functional recovery. Furthermore, initial consciousness (OR=3.013, p=0.014) hematoma location (lobar, OR=2.653, p=0.003), ventricular extension of blood (OR=2.077, p=0.013), leukocytosis (OR=2.048, p=0.008), alcohol intake (drinker, OR=1.927, p=0.023), and increased serum aminotransferase (OR=1.892, p=0.035) were found to be independent predictors of 90-day functional recovery after PICH. On the other hand, a pupillary abnormality (OR=4.532, p=0.000) and initial unconsciousness (OR=3.362, p=0.000) were found to be independent predictors of 30-day mortality after PICH. Conclusion The predictors of mortality and functional recovery after PICH identified during this analysis may assist during clinical decision-making, when advising patients or family members about the prognosis of PICH and when planning intervention trials. PMID:19609417

  15. STS-90 Day 09 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this ninth day of the STS-90 mission, the sleep period of the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk, is interrupted due to problems with equipment that removes carbon dioxide from the cabin atmosphere. Because of this, Columbia's crew went to bed about two hours later than scheduled.

  16. STS-90 Day 04 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this forth day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk continue work with the Escher Staircase Behavior Testing of Adult Rats experiment. This is the first of two behavior testing sessions with the adult rats being used for this experiment. The rats will have a 'hyper drive' unit placed on their head which has recording electrodes made of microscopic wires that are positioned in the brain to record activity in the hippocampus. The hippocampus is that portion of the brain used to develop spatial maps to help us navigate from one place to the other. With the 'hyper drive' units in place, the rats will then be put through a maze or on a track. While the rat is maneuvering on the maze or track, the cell activity of the hippocampus will be measured and recorded.

  17. STS-90 Day 14 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this fourteenth day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk focus on the efforts of Neurolab's Neuronal Plasticity Team to better understand how the adult nervous system adapts to the new environment of space. Columbia's science crew -- Mission Specialists Rick Linnehan and Dave Williams and Payload Specialists Jay Buckey and Jim Pawelczyk -- perform the second and final in-flight dissections of the adult male rats on board. The crew euthanizes and dissects nine rats and remove the vestibular or balance organs of the inner ear; the cerebellum, the part of the brain critical for maintaining balance and for processing information from the limbs so they can be moved smoothly; and the cerebrum, one part of which controls automatic functions such as body temperature regulation and the body's internal clock, and the cortical region that controls cognitive functions such as thinking. The first dissection, which was performed on the second day of the flight, went extremely well, according to Neurolab scientists.

  18. Percutaneous reduction of mitral valve regurgitation using the MitraClip system - immediate and 90-day follow-up of 3 cases.

    PubMed

    Kübler, Piotr; Kustrzycka-Kratochwil, Dorota; Telichowski, Artur; Witkowski, Tomasz; Banasiak, Waldemar; Jankowska, Ewa A; Ponikowski, Piotr; Reczuch, Krzysztof

    2013-01-01

    Treatment of hemodynamically significant valvular heart diseases has been the domain of cardiac surgery for decades. However, a promising novel method is the MitraClip system, involving percutaneous connection of insufficient valve leaflets with special cobalt-chrome clips. Our study presents clinical characteristics, course of treatment with the MitraClip system, and immediate and 90-day clinical and echocardiographic follow-up of the first 3 patients treated in our institution. Subsequently, based on data from the literature and our own experience, the current position around the world, and the target group of patients who are most likely to benefit from treatment using the MitraClip system, are discussed.

  19. 40 CFR 79.61 - Vehicle emissions inhalation exposure guideline.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., densities and shapes, and to predict where in the respiratory tract such particles may be deposited. It... to particles which are capable of being inhaled and may be deposited anywhere within the respiratory...) Principles and design criteria of inhalation exposure systems. Proper conduct of inhalation toxicity...

  20. Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double-blind placebo-controlled randomized trial.

    PubMed

    Stough, Con; Downey, Luke A; Lloyd, Jenny; Silber, Beata; Redman, Stephanie; Hutchison, Chris; Wesnes, Keith; Nathan, Pradeep J

    2008-12-01

    While Ayurvedic medicine has touted the cognitive enhancing effects of Bacopa monniera for centuries, there is a need for double-blind placebo-controlled investigations. One hundred and seven healthy participants were recruited for this double-blind placebo-controlled independent group design investigation. Sixty-two participants completed the study with 80% treatment compliance. Neuropsychological testing using the Cognitive Drug Research cognitive assessment system was conducted at baseline and after 90 days of treatment with a special extract of Bacopa monniera (2 x 150 mg KeenMind) or placebo. The Bacopa monniera product significantly improved performance on the 'Working Memory' factor, more specifically spatial working memory accuracy. The number of false-positives recorded in the Rapid visual information processing task was also reduced for the Bacopa monniera group following the treatment period. The current study provides support for the two other published studies reporting cognitive enhancing effects in healthy humans after a 90 day administration of the Bacopa monniera extract. Further studies are required to ascertain the effective dosage range, the time required to attain therapeutic levels and the effects over a longer term of administration.

  1. A 90-day subchronic feeding study of genetically modified maize expressing Cry1Ac-M protein in Sprague-Dawley rats.

    PubMed

    Liu, Pengfei; He, Xiaoyun; Chen, Delong; Luo, Yunbo; Cao, Sishuo; Song, Huan; Liu, Ting; Huang, Kunlun; Xu, Wentao

    2012-09-01

    The cry1Ac-M gene, coding one of Bacillus thuringiensis (Bt) crystal proteins, was introduced into maize H99 × Hi IIB genome to produce insect-resistant GM maize BT-38. The food safety assessment of the BT-38 maize was conducted in Sprague-Dawley rats by a 90-days feeding study. We incorporated maize grains from BT-38 and H99 × Hi IIB into rodent diets at three concentrations (12.5%, 25%, 50%) and administered to Sprague-Dawley rats (n=10/sex/group) for 90 days. A commercialized rodent diet was fed to an additional group as control group. Body weight, feed consumption and toxicological response variables were measured, and gross as well as microscopic pathology were examined. Moreover, detection of residual Cry1Ac-M protein in the serum of rats fed with GM maize was conducted. No death or adverse effects were observed in the current feeding study. No adverse differences in the values of the response variables were observed between rats that consumed diets containing GM maize BT-38 and non-GM maize H99 × Hi IIB. No detectable Cry1Ac-M protein was found in the serum of rats after feeding diets containing GM maize for 3 months. The results demonstrated that BT-38 maize is as safe as conventional non-GM maize.

  2. Inhalation Injury.

    DTIC Science & Technology

    1994-01-01

    alpha,-antitrypsin resulting cur most often as the result of tracheal in prolonged action of proteases such as or laryngeal damage from the endotra... curs is determined by physicochemical Turbulent airflow, such as at bifurca- properties of the inhaled substance, its tions of the airway, separates

  3. Past, present and emerging toxicity issues for jet fuel

    SciTech Connect

    Mattie, David R.

    2011-07-15

    The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels.

  4. Secondary prevention lifestyle interventions initiated within 90 days after TIA or ‘minor’ stroke: a systematic review and meta-analysis of rehabilitation programmes

    PubMed Central

    Heron, Neil; Kee, Frank; Cardwell, Christopher; Tully, Mark A; Donnelly, Michael; Cupples, Margaret E

    2017-01-01

    Background Strokes are often preceded by a transient ischaemic attack (TIA) or ‘minor’ stroke. The immediate period after a TIA/minor stroke is a crucial time to initiate secondary prevention. However, the optimal approach to prevention, including non-pharmacological measures, after TIA is not clear. Aim To systematically review evidence about the effectiveness of delivering secondary prevention, with lifestyle interventions, in comprehensive rehabilitation programmes, initiated within 90 days of a TIA/minor stroke. Also, to categorise the specific behaviour change techniques used. Design and setting The review identified randomised controlled trials by searching the Cochrane Library, Ovid MEDLINE, Ovid EMBASE, Web of Science, EBSCO CINAHL and Ovid PsycINFO. Method Two review authors independently screened titles and abstracts for eligibility (programmes initiated within 90 days of event; outcomes reported for TIA/minor stroke) and extracted relevant data from appraised studies; a meta-analysis was used to synthesise the results. Results A total of 31 potentially eligible papers were identified and four studies, comprising 774 patients post-TIA or minor stroke, met the inclusion criteria; two had poor methodological quality. Individual studies reported increased aerobic capacity but meta-analysis found no significant change in resting and peak systolic blood pressure, resting heart rate, aerobic capacity, falls, or mortality. The main behaviour change techniques were goal setting and instructions about how to perform given behaviours. Conclusion There is limited evidence of the effectiveness of early post-TIA rehabilitation programmes with preventive lifestyle interventions. Further robust randomised controlled trials of comprehensive rehabilitation programmes that promote secondary prevention and lifestyle modification immediately after a TIA are needed. PMID:27919935

  5. Vertical jump performance after 90 days bed rest with and without flywheel resistive exercise, including a 180 days follow-up.

    PubMed

    Rittweger, Jörn; Felsenberg, Dieter; Maganaris, Constantinos; Ferretti, José Luis

    2007-07-01

    Muscle atrophy and neuromuscular de-conditioning occur in response to space flight and bed-rest. In this study, we investigated the efficacy of flywheel training to conserve jumping power and height during 90 days bed rest. Twenty-four young healthy men underwent strict bed-rest (-6 degrees head down tilt) for 90 days. Eight participants were assigned to a flywheel group (FW) and 16 to a control group (Ctrl). The ground reaction force was measured during vertical jump tests twice during baseline data collection, and on day 4, 7, 14, 90 and 180 of recovery. In half of the participants, jump tests were also performed within minutes after re-ambulation and on four more occasions during the first 2 days of recovery. Jump height was reduced from 40.6 cm (SD 6.1 cm) during the first baseline measurement to 27.6 cm (SD 5.6 cm) on day 4 of recovery in Ctrl, but only from 38.6 cm (SD 3.9 cm) to 34.4 cm (SD 6.5 cm) in FW (P < 0.001). At the same time, peak power was reduced from 47.4 W/kg (SD 8.0 W/kg) to 34.5 W/kg in Ctrl, but only from 46.2 W/kg (6.0 W/kg) to 42.2 W/kg SD 4.6 W/kg) in FW (P < 0.001). Jump height and peak power were completely recovered after 163 and 140 days in Ctrl, respectively, and after 72 and 18 days in FW (regression analysis). In conclusion, flywheel exercise could effectively offset neuromuscular de-conditioning during bed-rest, and led to full recovery at an earlier stage. These findings nourish the hope that adequate training paradigms can fully sustain neuromuscular function under microgravity conditions.

  6. A functional variant in the 3ˈ-UTR of VEGF predicts the 90-day outcome of ischemic stroke in Chinese patients

    PubMed Central

    Jin, Lei; Weng, Yingfeng; Wang, Yujie; Wu, Hui; Li, Xia; Huang, Ying; Wang, Shengyue

    2017-01-01

    Vascular endothelial growth factor (VEGF) plays critical roles in angiogenesis and vasculogenesis, which are associated with post-stroke functional recovery. However, the effects of the VEGFA polymorphisms on the outcome of ischemic stroke (IS) have been rarely reported. We therefore investigated the associations of +936C/T variant (rs3025039) with the susceptibilities and the 90-day outcomes from 494 IS patients and 337 healthy controls in Chinese population through the establishment of logistic multivariate regression model. Stroke severity at admission and outcome of 90 days were respectively assessed according to the National Institutes of Health Stroke Scale and the modified Rankin Scale. The analysis showed that there were no significant associations of the rs3025039 genotypes with the susceptibility (P = 0.229) and the severity (P = 0.734). However, when we divided the 308 IS patients into two groups according to the different outcomes, we found that the rs3025039 TC+TT genotype significantly increased the risk of poor recovery [adjusted odds ratio (OR), 1.99; 95% confidence interval (CI), 1.18–3.37]. Interestingly, we observed another 3ˈUTR variant, +1451C/T (rs3025040), exhibited strong linkage disequilibrium (r2 = 1.0) with +936C/T and was located in a predicted microRNA-binding site. The rs3025040 T allele significantly decreased the luciferase activities in four cell lines, which indicated a potential disruption of the miRNA-mRNA interaction that would result in lower VEGF expression levels. Our data suggested that the +936C/T variants significantly increased the risk of poorer stroke outcome by affecting the bindings of miR-199a and miR-199b to VEGF mRNA at the rs30250340 polymorphic site. PMID:28234972

  7. Toxicity evaluation of exposure to an atmospheric mixture of polychlorinated biphenyls by nose-only and whole-body inhalation regimens

    PubMed Central

    Hu, Xin; Adamcakova-Dodd, Andrea; Lehmler, Hans-Joachim; Thorne, Peter S.

    2016-01-01

    The health risk of inhalation exposure to polychlorinated biphenyls (PCB) cannot be assessed due to the lack of rigorous inhalation studies providing a low dose effect level. One large uncertainty rests on the exposure regimen. Whole-body exposure systems allow oral PCB intake that confounds the exposure. Thus, we sought to compare the whole-body and nose-only exposure methods by conducting contemporaneous PCB inhalation exposures. Vapor-phase PCBs were generated from the Chicago Air Mixture supplemented with PCB 11 (CAM+). Female Sprague-Dawley rats were exposed concurrently to a PCB concentration of 533 ± 93 µg/m3, 4 h/day, 6 days/week, for 4 weeks. Congener-specific analysis using gas chromatography– mass spectrometry (GC/MS) showed higher total PCB concentration in the lungs of nose-only exposed animals than the whole-body exposed, resulting in a higher dose level for nose-only group. Congener profiles were consistent among exposure groups and tissue types and were dominated by PCB 28/31 and higher-chlorinated congeners reflecting rapid metabolism of other lower-chlorinated PCBs. No significant change was seen regarding metabolic enzyme expression, glutathione, or histopathology. However, diminished weight gain and reduced plasma total thyroxine levels were found in both groups compared with controls, with stronger response in the nose-only group. Lipid peroxidation was also elevated in the liver of nose-only exposed animals. We conclude that nose-only exposure was the preferred regimen for 4-wk PCB inhalation studies and thyroid hormone dysregulation was observed at an estimated dose of 1320 µg/kg b.w., providing information on a preliminary lowest-observed-adverse-effect-level (LOAEL). PMID:26348937

  8. Levalbuterol Oral Inhalation

    MedlinePlus

    Levalbuterol comes as a solution (liquid) to inhale by mouth using a nebulizer (machine that turns medication into a mist that can be inhaled), a concentrated solution to be mixed with normal saline and inhaled ...

  9. Collagen content in the vastus lateralis and the soleus muscle following a 90-day bed rest period with or without resistance exercises

    PubMed Central

    Nielsen, Rasmus Oestergaard; Schjerling, Peter; Tesch, Per; Stål, Per; Langberg, Henning

    2015-01-01

    Summary Introduction spaceflight seems associated with deterioration of the function of the skeletal muscles. Since muscle collagen is critical for muscle function, an improved understanding of the content of the muscle collagen during long-term inactivity seems important. Bed-rest with in-bed resistance training serves as a proxy for the conditions in space. Therefore, ground-based studies may improve the understanding of the consequences of long-term inactivity. Purpose the purpose is to compare the change in collagen protein in the vastus lateralis (VL) and the soleus (SOL) muscle amongst persons exposed to a 90-day bed rest with or without resistance exercise. Methods an explorative analysis was completed based on data from a randomized, controlled trial. The intervention group (BRE, SOL n=4, VL n=8) performed supine-based squat exercises, whereas the controls (BE, SOL n=6, VL n=12) remained inactive during follow-up. Muscle biopsies from vastus lateralis and soleus were taken at baseline (pre) and after 90-days’ follow-up (post). Muscle collagen (μg collagen/mg protein) was quantified. Two-way repeated measurements ANOVA was used to compare the interaction between the intervention (BRE/BR) and time (pre/post) for each muscle. Results the collagen content of VL was similar between pre and post in the BRE group (−3.8 μg collagen/mg protein [95% CI: −22.0; 14.4], p=0.68) while it rose amongst individuals in the BR group (14.9 μg collagen/mg protein [95% CI: −0.01; 29.7], p=0.05). The difference of 18.66 [95% CI: −6.5; 43.9] between BRE and BR across time was, however, not significant (p=0.14). No significant reduction in SOL muscle collagen content was observed from pre to post in the BR group (−9.3 μg collagen/mg protein [95% CI: −24.9; 6.4], p=0.25) or in the BRE group (−6.5 μg collagen/mg protein [95% CI: −25.6; 12.6], p=0.50). There was no difference in the effect of BR versus BRE over time (mean difference −2.78 μg collagen

  10. A 90 day safety assessment of genetically modified rice expressing Cry1Ab/1Ac protein using an aquatic animal model.

    PubMed

    Zhu, Hao-Jun; Chen, Yi; Li, Yun-He; Wang, Jia-Mei; Ding, Jia-Tong; Chen, Xiu-Ping; Peng, Yu-Fa

    2015-04-15

    In fields of transgenic Bt rice, frogs are exposed to Bt proteins through consumption of both target and nontarget insects. In the present study, we assessed the risk posed by transgenic rice expressing a Cry1Ab/1Ac fusion protein (Huahui 1, HH1) on the development of Xenopus laevis. For 90 days, froglets were fed a diet with 30% HH1 rice, 30% parental rice (Minghui 63, MH63), or no rice as a control. Body weight and length were measured every 15 days. After sacrificing the froglets, we performed a range of biological, clinical, and pathological assessments. No significant differences were found in body weight (on day 90: 27.7 ± 2.17, 27.4 ± 2.40, and 27.9 ± 1.67 g for HH1, MH63, and control, respectively), body length (on day 90: 60.2 ± 1.55, 59.3 ± 2.33, and 59.7 ± 1.64 mm for HH1, MH63, and control, respectively), animal behavior, organ weight, liver and kidney function, or the microstructure of some tissues between the froglets fed on the HH1-containing diet and those fed on the MH63-containing or control diets. This indicates that frog development was not adversely affected by dietary intake of Cry1Ab/1Ac protein.

  11. Phase II, Randomized, Placebo-controlled, 90-day Study of Emixustat HCL in Geographic Atrophy Associated with Dry Age-Related Macular Degeneration

    PubMed Central

    Dugel, Pravin U.; Novack, Roger L.; Csaky, Karl G.; Richmond, Preston P.; Birch, David G.; Kubota, Ryo

    2015-01-01

    Purpose This study assessed the safety, tolerability, and pharmacodynamics of emixustat hydrochloride (ACU-4429), a novel visual cycle modulator, in subjects with geographic atrophy (GA) associated with dry age-related macular degeneration (AMD). Methods Subjects were randomly assigned to oral emixustat (2, 5, 7, or 10 mg once daily) or placebo (3:1 ratio) for 90 days. Recovery of rod photoreceptor sensitivity following a photobleach was measured by electroretinography. Safety evaluations included analysis of adverse events (AEs) and ophthalmic examinations. Results Seventy-two subjects (54 emixustat, 18 placebo) were evaluated. Emixustat suppressed rod photoreceptor sensitivity in a dose-dependent manner. Suppression plateaued by Day 14, and was reversible within 7-14 days after drug cessation. No systemic AEs of concern were noted. Dose-related ocular AEs (chromatopsia, 57% emixustat vs. 17% placebo; and delayed dark adaptation, 48% emixustat vs. 6% placebo) were mild to moderate, and the majority resolved on study or within 7-14 days after study drug cessation. Conclusions In this phase II study, emixustat produced a dose-dependent, reversible effect on rod function, and an ocular AE profile that is consistent with the proposed mechanism of action. These results support further testing of emixustat for the treatment of GA associated with dry AMD. PMID:25932553

  12. Safety assessment of SDA soybean oil: results of a 28-day gavage study and a 90-day/one generation reproduction feeding study in rats.

    PubMed

    Hammond, Bruce G; Lemen, Joan K; Ahmed, Gulam; Miller, Kathleen D; Kirkpatrick, Jeannie; Fleeman, Tammye

    2008-12-01

    Long chain polyunsaturated fatty acids (LC-PUFAs) in the diet reduce risk of cardiac mortality. Fish oils are a dietary source of LC-PUFAs (EPA, DHA) but intake is low in Western diets. Adding beneficial amounts of LC-PUFAs to foods is limited by their instability and potential to impart off-flavors. Stearidonic acid (SDA), a precursor of EPA in man, is more stable than EPA/DHA in food matrices. SDA is present in fish oils (0.5-4%) and in nutraceuticals (echium, borage oil). Genes for Delta6, Delta15 desaturases were introduced into soybeans that convert linoleic and alpha-linolenic acid to SDA (15-30% fatty acids). Since addition of SDA soybean oil into human foods increases SDA intake, toxicology studies were undertaken to assess its safety. In a 28-day pilot study, rats were gavaged with SDA soybean oil at dosages up to 3g/kg body weight/day; no treatment-related adverse effects were observed. A 90-day/one generation rat reproduction study was subsequently conducted where SDA soybean oil was added to diets to provide daily doses of 1.5 and 4 g/kg body weight. There were no treatment-related adverse effects on parental animals or on reproductive performance and progeny development.

  13. Assessment of the reporting of quality and outcome measures in hepatic resections: a call for 90-day reporting in all hepatectomy series

    PubMed Central

    Egger, Michael E; Ohlendorf, Joanna M; Scoggins, Charles R; McMasters, Kelly M; Martin, Robert C G

    2015-01-01

    Background The aim of this paper is to assess the current state of quality and outcomes measures being reported for hepatic resections in the recent literature. Methods Medline and PubMed databases were searched for English language articles published between 1 January 2002 and 30 April 2013. Two examiners reviewed each article and relevant citations for appropriateness of inclusion, which excluded papers of liver donor hepatic resections, repeat hepatectomies or meta-analyses. Data were extracted and summarized by two examiners for analysis. Results Fifty-five studies were identified with suitable reporting to assess peri-operative mortality in hepatic resections. In only 35% (19/55) of the studies was the follow-up time explicitly stated, and in 47% (26/55) of studies peri-operative mortality was limited to in-hospital or 30 days. The time period in which complications were captured was not explicitly stated in 19 out of 28 studies. The remaining studies only captured complications within 30 days of the index operation (8/28). There was a paucity of quality literature addressing truly patient-centred outcomes. Conclusion Quality outcomes after a hepatic resection are inconsistently reported in the literature. Quality outcome studies for a hepatectomy should report mortality and morbidity at a minimum of 90 days after surgery. PMID:26228262

  14. Inhalation Toxicology. V. Evaluation of Relative Toxicity to Rats of Thermal Decomposition Products from Two Aircraft Seat Fire-Blocking Materials.

    DTIC Science & Technology

    1985-11-01

    only. The relative toxicity of the combustion gases was measured by determining time-to-incapacitation (ti) in the laboratory rat , the same endpoint... the laboratory rat was the measured response used to compare the relative toxicity of the combustion gases produced from the two materials. Because of

  15. Toxicity of aerosols of nicotine and pyruvic acid (separate and combined) in Sprague-Dawley rats in a 28-day OECD 412 inhalation study and assessment of systems toxicology.

    PubMed

    Phillips, Blaine; Esposito, Marco; Verbeeck, Jan; Boué, Stéphanie; Iskandar, Anita; Vuillaume, Gregory; Leroy, Patrice; Krishnan, Subash; Kogel, Ulrike; Utan, Aneli; Schlage, Walter K; Bera, Monali; Veljkovic, Emilija; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

    2015-01-01

    Toxicity of nebulized nicotine (Nic) and nicotine/pyruvic acid mixtures (Nic/Pyr) was characterized in a 28-day Organization for Economic Co-operation and Development 412 inhalation study with additional transcriptomic and lipidomic analyses. Sprague-Dawley rats were nose-only exposed, 6 h/day, 5 days/week to filtered air, saline, nicotine (50 µg/l), sodium pyruvate (NaPyr, 33.9 µg/l) or equimolar Nic/Pyr mixtures (18, 25 and 50 µg nicotine/l). Saline and NaPyr caused no health effects, but rats exposed to nicotine-containing aerosols had decreased body weight gains and concentration-dependent increases in liver weight. Blood neutrophil counts were increased and lymphocyte counts decreased in rats exposed to nicotine; activities of alkaline phosphatase and alanine aminotransferase were increased, and levels of cholesterol and glucose decreased. The only histopathologic finding in non-respiratory tract organs was increased liver vacuolation and glycogen content. Respiratory tract findings upon nicotine exposure (but also some phosphate-buffered saline aerosol effects) were observed only in the larynx and were limited to adaptive changes. Gene expression changes in the lung and liver were very weak. Nic and Nic/Pyr caused few significant changes (including Cyp1a1 gene upregulation). Changes were predominantly related to energy metabolism and fatty acid metabolism but did not indicate an obvious toxicity-related response. Nicotine exposure lowered plasma lipids, including cholesteryl ester (CE) and free cholesterol and, in the liver, phospholipids and sphingolipids. Nic, NaPyr and Nic/Pyr decreased hepatic triacylglycerol and CE. In the lung, Nic and Nic/Pyr increased CE levels. These data suggest that only minor biologic effects related to inhalation of Nic or Nic/Pyr aerosols were observed in this 28-day study.

  16. Evaluation of two different metabolic hypotheses for dichloromethane toxicity using physiologically based pharmacokinetic modeling for in vivo inhalation gas uptake data exposure in female B6C3F1 mice

    SciTech Connect

    Evans, M.V.; Caldwell, J.C.

    2010-05-01

    Dichloromethane (DCM, methylene chloride) is a lipophilic volatile compound readily absorbed and then metabolized to several metabolites that may lead to chronic toxicity in different target organs. Physiologically based pharmacokinetic (PBPK) models are useful tools for calculation of internal and target organ doses of parent compound and metabolites. PBPK models, coupled with in vivo inhalation gas-uptake data, can be useful to estimate total metabolism. Previously, such an approach was used to make predictions regarding the metabolism and to make subsequent inferences of DCM's mode of action for toxicity. However, current evidence warrants re-examination of this approach. The goal of this work was to examine two different hypotheses for DCM metabolism in mice. One hypothesis describes two metabolic pathways: one involving cytochrome P450 2E1 (CYP2E1) and a second glutathione (GSH). The second metabolic hypothesis describes only one pathway mediated by CYP2E1 that includes multiple binding sites. The results of our analysis show that the in vivo gas-uptake data fit both hypotheses well and the traditional analysis of the chamber concentration data is not sufficient to distinguish between them. Gas-uptake data were re-analyzed by construction of a velocity plot as a function of increasing DCM initial concentration. The velocity (slope) analysis revealed that there are two substantially different phases in velocity, one rate for lower exposures and a different rate for higher exposures. The concept of a 'metabolic switch,' namely that due to conformational changes in the enzyme after one site is occupied - a different metabolic rate is seen - is also consistent with the experimental data. Our analyses raise questions concerning the importance of GSH metabolism for DCM. Recent research results also question the importance of this pathway in the toxicity of DCM. GSH-related DNA adducts were not formed after in vivo DCM exposure in mice and DCM-induced DNA damage has

  17. Muscle atrophy and bone loss after 90 days' bed rest and the effects of flywheel resistive exercise and pamidronate: results from the LTBR study.

    PubMed

    Rittweger, Jörn; Frost, Harold M; Schiessl, Hans; Ohshima, Hiroshi; Alkner, Björn; Tesch, Per; Felsenberg, Dieter

    2005-06-01

    Muscle atrophy and bone loss pose substantial problems for long-term space flight and in clinical immobilization. We therefore tested the efficacy of flywheel resistive exercise and pamidronate to counteract such losses. Twenty five young healthy males underwent strict bed rest with -6 degrees head-down tilt for 90 days. Subjects were randomized into an exercise group that practiced resistive exercise with a 'flywheel' (FW) device every 2-3 days, a pamidronate group (Pam) that received 60 mg pamidronate i.v. 14 days prior to bed rest and a control group (Ctrl) that received none of these countermeasures. During the study, Ca(++) and protein intake were controlled. Peripheral quantitative computed tomography (pQCT) was used to assess bone mineral content (BMC) and muscle cross sectional area (mCSA) of calf and forearm. Measurements were taken twice during baseline data collection, after 28 and after 89 days bed rest, and after 14 days recovery. On the same days, urinary Pyridinoline excretion and serum levels of alkaline phosphatase, Ca(++) and PTH were measured. Pre-study exercise habits were assessed through the Freiburg questionnaire. Losses in calf mCSA were significantly reduced in FW (Ctrl: -25.6% +/- 2.5% Pam: -25.6% +/- 3.7%, FW: -17.3% +/- 2.7%), but not in the forearm mCSA (Ctrl: -6.4% +/- 4.33%, Pam: -7.7% +/- 4.1%, FW: -7.6% +/- 3.3%). Both diaphyseal and epiphyseal BMC losses of the tibia were mitigated in Pam and FW as compared to Ctrl, although this was significant only at the diaphysis. Inter-individual variability was significantly greater for changes in BMC than in mCSA, and correlation of BMC losses was poor among different locations of the tibia. A significant positive correlation was found between change in tibia epiphyseal BMC and serum cortisol levels. These findings suggest that both countermeasures are only partly effective to preserve BMC (FW and Pam) and mCSA (FW) of the lower leg during bed rest. The partial efficacy of flywheel exercise

  18. Inhalation Therapy in Horses.

    PubMed

    Cha, Mandy L; Costa, Lais R R

    2017-04-01

    This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials.

  19. Exposure to Pb, Cd, and As mixtures potentiates the production of oxidative stress precursors: 30-day, 90-day, and 180-day drinking water studies in rats

    SciTech Connect

    Whittaker, Margaret H.; Wang, Gensheng; Chen Xueqing; Lipsky, Michael; Smith, Donald; Gwiazda, Roberto; Fowler, Bruce A.

    2011-07-15

    Exposure to chemical mixtures is a common and important determinant of toxicity and is of particular concern due to their appearance in sources of drinking water. Despite this, few in vivo mixture studies have been conducted to date to understand the health impact of chemical mixtures compared to single chemicals. Interactive effects of lead (Pb), cadmium (Cd) and arsenic (As) were evaluated in 30-, 90-, and 180-day factorial design drinking water studies in rats designed to test the hypothesis that ingestion of such mixtures at individual component Lowest-Observed-Effect-Levels (LOELs) results in increased levels of the pro-oxidant delta aminolevulinic acid (ALA), iron, and copper. LOEL levels of Pb, Cd, and As mixtures resulted in the increased presence of mediators of oxidative stress such as ALA, copper, and iron. ALA increases were followed by statistically significant increases in kidney copper in the 90- and 180-day studies. Statistical evidence of interaction was identified for six biologically relevant variables: blood delta aminolevulinic acid dehydratase (ALAD), kidney ALAD, urinary ALA, urinary iron, kidney iron, and kidney copper. The current investigations underscore the importance of considering interactive effects that common toxic agents such as Pb, Cd, and As may have upon one another at low-dose levels. The interactions between known toxic trace elements at biologically relevant concentrations shown here demonstrate a clear need to rigorously review methods by which national/international agencies assess health risks of chemicals, since exposures may commonly occur as complex mixtures.

  20. Exposure to Pb, Cd, and As mixtures potentiates the production of oxidative stress precursors: 30-day, 90-day, and 180-day drinking water studies in rats.

    PubMed

    Whittaker, Margaret H; Wang, Gensheng; Chen, Xue-Qing; Lipsky, Michael; Smith, Donald; Gwiazda, Roberto; Fowler, Bruce A

    2011-07-15

    Exposure to chemical mixtures is a common and important determinant of toxicity and is of particular concern due to their appearance in sources of drinking water. Despite this, few in vivo mixture studies have been conducted to date to understand the health impact of chemical mixtures compared to single chemicals. Interactive effects of lead (Pb), cadmium (Cd) and arsenic (As) were evaluated in 30-, 90-, and 180-day factorial design drinking water studies in rats designed to test the hypothesis that ingestion of such mixtures at individual component Lowest-Observed-Effect-Levels (LOELs) results in increased levels of the pro-oxidant delta aminolevulinic acid (ALA), iron, and copper. LOEL levels of Pb, Cd, and As mixtures resulted in the increased presence of mediators of oxidative stress such as ALA, copper, and iron. ALA increases were followed by statistically significant increases in kidney copper in the 90- and 180-day studies. Statistical evidence of interaction was identified for six biologically relevant variables: blood delta aminolevulinic acid dehydratase (ALAD), kidney ALAD, urinary ALA, urinary iron, kidney iron, and kidney copper. The current investigations underscore the importance of considering interactive effects that common toxic agents such as Pb, Cd, and As may have upon one another at low-dose levels. The interactions between known toxic trace elements at biologically relevant concentrations shown here demonstrate a clear need to rigorously review methods by which national/international agencies assess health risks of chemicals, since exposures may commonly occur as complex mixtures.

  1. Formoterol Oral Inhalation

    MedlinePlus

    ... until you are ready to inhale your dose. Pull off the inhaler cover and twist the mouthpiece open in the direction shown by the arrow on the mouthpiece. Push the buttons on each side to be sure ...

  2. Albuterol Oral Inhalation

    MedlinePlus

    Albuterol is used to prevent and treat difficulty breathing, wheezing, shortness of breath, coughing, and chest tightness ... for oral inhalation is also used to prevent breathing difficulties during exercise. Albuterol inhalation aerosol (Proair HFA, ...

  3. Smoke inhalation injury

    NASA Astrophysics Data System (ADS)

    Birky, M.

    The cause of death by fires was studied. The present results and information are, however, not enough to reduce loss of life or inhalation injury. The magnitude and type of inhalation injury for civilians and firefighters represents the most inadequately defined human element of accidental fires. Little information is available on compounds other than carbon monoxide, which are responsible for respiration injury or toxicological syndrome. Effective treatment methods for inhalation victims and studies on fatalities, inhalation injury and animals are suggested.

  4. Dry powder inhalers of gentamicin and leucine: formulation parameters, aerosol performance and in vitro toxicity on CuFi1 cells.

    PubMed

    Aquino, R P; Prota, L; Auriemma, G; Santoro, A; Mencherini, T; Colombo, G; Russo, P

    2012-04-15

    The high hygroscopicity of gentamicin (G) as raw material hampers the production of respirable particles during aerosol generation and prevents its direct use as powder for inhalation in patients suffering from cystic fibrosis (CF). Therefore, this research aimed to design a new dry powder formulation of G studying dispersibility properties of an aminoacid, L-leucine (leu), and appropriate process conditions. Spray-dried powders were characterized as to water uptake, particle size distribution, morphology and stability, in correlation with process parameters. Aerodynamic properties were analyzed both by Single Stage Glass Impinger and Andersen Cascade Impactor. Moreover, the potential cytotoxicity on bronchial epithelial cells bearing a CFTR F508/F508 mutant genotype (CuFi1) were tested. Results indicated that leu may improve the aerosol performance of G-dried powders. The maximum fine particle fraction (FPF) of about 58.3% was obtained when water/isopropyl alcohol 7:3 system and 15-20% (w/w) of leu were used, compared to a FPF value of 13.4% for neat G-dried powders. The enhancement of aerosol efficiency was credited both to the improvement of the powder flowability, caused by the dispersibility enhancer (aminoacid), and to the modification of the particle surface due to the influence of the organic co-solvent on drying process. No significant degradation of the dry powder was observed up to 6 months of storage. Moreover, particle engineering did not affect either the cell viability or cell proliferation of CuFi1 over a 24 h period.

  5. Oxidative Stress, Inflammatory Biomarkers, and Toxicity in Mouse Lung and Liver After Inhalation Exposure to 100% Biodiesel or Petroleum Diesel Emissions

    PubMed Central

    Shvedova, Anna A.; Yanamala, Naveena; Murray, Ashley R.; Kisin, Elena R.; Khaliullin, Timur; Hatfield, Meghan K.; Tkach, Alexey V.; Krantz, Q. T.; Nash, David; King, Charly; Gilmour, M. Ian; Gavett, Stephen H.

    2015-01-01

    Over the past decade, soy biodiesel (BD) has become a first alternative energy source that is economically viable and meets requirements of the Clean Air Act. Due to lower mass emissions and reduced hazardous compounds compared to diesel combustion emissions (CE), BD exposure is proposed to produce fewer adverse health effects. However, considering the broad use of BD and its blends in different industries, this assertion needs to be supported and validated by mechanistic and toxicological data. Here, adverse effects were compared in lungs and liver of BALB/cJ mice after inhalation exposure (0, 50, 150, or 500 μg/m3; 4 h/d, 5 d/wk, for 4 wk) to CE from 100% biodiesel (B100) and diesel (D100). Compared to D100, B100 CE produced a significant accumulation of oxidatively modified proteins (carbonyls), an increase in 4-hydroxynonenal (4-HNE), a reduction of protein thiols, a depletion of antioxidant gluthatione (GSH), a dose-related rise in the levels of biomarkers of tissue damage (lactate dehydrogenase, LDH) in lungs, and inflammation (myeloperoxidase, MPO) in both lungs and liver. Significant differences in the levels of inflammatory cytokines interleukin (IL)-6, IL-10, IL-12p70, monocyte chemoattractant protein (MCP)-1, interferon (IFN) γ, and tumor necrosis factor (TNF)-α were detected in lungs and liver upon B100 and D100 CE exposures. Overall, the tissue damage, oxidative stress, inflammation, and cytokine response were more pronounced in mice exposed to BD CE. Further studies are required to understand what combustion products in BD CE accelerate oxidative and inflammatory responses. PMID:24156694

  6. Focus on Inhalants.

    ERIC Educational Resources Information Center

    Challenge: Safe, Disciplines, and Drug-Free Schools, 1994

    1994-01-01

    The use of inhalants is a major health concern among the school-age population. Information presented in this publication dispels the myths about inhalant use and presents common warning signs that alert teachers to a student's use. The short- and long-term effects of inhalant use are described to shed light on the health risks involved. Lesson…

  7. Inhalation injury: epidemiology, pathology, treatment strategies

    PubMed Central

    2013-01-01

    from European centers supports application of specific antidotes for cyanide toxicity. Consistent international support for this therapy is lacking. Even diagnostic criteria are not consistently applied though bronchoscopy is one diagnostic and therapeutic tool. Medical strategies under investigation for specific treatment of smoke inhalation include beta-agonists, pulmonary blood flow modifiers, anticoagulants and antiinflammatory strategies. Until the value of these and other approaches is confirmed, however, the clinical approach to inhalation injury is supportive. PMID:23597126

  8. Safety evaluation of AB-LIFE(®) (Lactobacillus plantarum CECT 7527, 7528 and 7529): Antibiotic resistance and 90-day repeated-dose study in rats.

    PubMed

    Mukerji, Pushkor; Roper, Jason M; Stahl, Buffy; Smith, Amy B; Burns, Frank; Rae, Jessica Caverly; Yeung, Nicolas; Lyra, Anna; Svärd, Laura; Saarinen, Markku T; Alhoniemi, Esa; Ibarra, Alvin; Ouwehand, Arthur C

    2016-06-01

    AB-LIFE(®) is a probiotic product consisting of equal parts of three strains of Lactobacillus plantarum (CECT 7527, 7528, and 7529) blended with inert excipients. Whole genome sequencing was performed on each of the three strains. Antibiotic resistance was evaluated by genomic mining for resistance genes, and assessment for transferability. No risk of transfer potential was identified for any antibiotic resistance genes in the three strains. AB-LIFE(®) was evaluated for potential subchronic oral toxicity in rats, with dosages of 300 and 1000 mg/kg BW/day (equivalent to 5.55 × 10(10) and 1.85 × 10(11) CFU/kg BW/day). Survival of the three test strains through the gastrointestinal tract was supported by fecal analysis. No adverse effects were identified with respect to in-life parameters, clinical or anatomic pathology, translocation, or fecal chemical analyses. The no-observed-adverse-effect level (NOAEL) for AB-LIFE(®) in male and female rats was 1000 mg/kg BW/day (1.85 × 10(11) CFU of AB-LIFE(®)/kg BW/day), the highest dose level evaluated. These results, in conjunction with a previous acute toxicity study in rats, support the conclusion that AB-LIFE(®) is safe for human consumption.

  9. A 90-day subchronic study of rats fed lean pork from genetically modified pigs with muscle-specific expression of recombinant follistatin.

    PubMed

    Zou, Shiying; Tang, Min; He, Xiaoyun; Cao, Yuan; Zhao, Jie; Xu, Wentao; Liang, Zhihong; Huang, Kunlun

    2015-11-01

    Because cardiovascular disease incidence has rapidly increased in recent years, people are choosing relatively healthier diets with low animal fat. A transgenic pig with low fat and a high percentage of lean meat was created in 2011; this pig overexpresses the follistatin (FST) gene. To evaluate the safety of lean pork derived from genetically modified (GM) pigs, a subchronic oral toxicity study was conducted using Sprague-Dawley rats. GM pork and non-GM pork were incorporated into the diet at levels of 3.75%, 7.5%, and 15% (w/w), and the main nutrients of the various diets were subsequently balanced. The safety of GM pork was assessed by comparison of the toxicology response variables in Sprague-Dawley rats consuming diets containing GM pork with those consuming non-GM pork. No treatment-related adverse or toxic effects were observed based on an examination of the daily clinical signs, body weight, food consumption, hematology, serum biochemistry, and organ weight or based on gross and histopathological examination. The results demonstrate that GM pork is as safe for consumption as conventional pork.

  10. Two-week inhalation toxicity of polymeric diphenylmethane-4, 4'-diisocyanate (PMDI) in rats: analysis of biochemical and morphological markers of early pulmonary response.

    PubMed

    Pauluhn, J; Emura, M; Mohr, U; Popp, A; Rosenbruch, M

    1999-12-01

    The pulmonary response of Wistar rats to respirable polymeric diphenylmethane-4,4'-diisocyanate (PMDI) aerosol was examined in a 2-wk repeated nose-only inhalation exposure study. Exposure concentrations were 1.1, 3.3, and 13.7 mg PMDI/m(3) (6 h/day, 15 exposures). The level of 13.7 mg/m(3) was actually a combination of an initial target concentration of 10 mg/m(3) in wk 1, which was raised to 16 mg/m(3) in wk 2, due to a lack of signs suggestive of pulmonary irritation. An acute sensory irritation study on rats served as basis for selection of these concentrations. Shortly after the 2-wk exposure period, rats were subjected to pulmonary function and arterial blood gas measurements. Lungs were examined by light and transmission electron microscopy, and labeling indices in terminal bronchioles were measured. Bronchoalveolar lavage (BAL) was performed to assess various indicators of pulmonary inflammation, including neutrophil and macrophage numbers, protein, lactate dehydrogenase (LDH), gamma-glutamyltranspeptidase (gamma-GT), alkaline phosphatase (APh), acid phosphatase (ACPh), and beta-N-acetylglucosaminidase (beta-NAG). Phosphatidylcholine in BAL fluid and BAL cells was determined as aggregated endpoint suggestive of changes in pulmonary surfactant. Rats exposed to 3.3 and 13.7 mg/m(3) experienced concentration-dependent signs of respiratory tract irritation. Determination of arterial blood gases, lung mechanics, and carbon monoxide diffusing capacity did not demonstrate specific effects. Analysis of BAL fluid and BAL cells revealed changes indicative of marked inflammatory response and/or cytotoxicity in rats exposed to 13.7 mg/m(3), and the changes were characterized by statistically significantly increased activities of LDH, beta-NAG, and protein. Phospholipid concentrations were increased in rats exposed to 1.1 mg/m(3) and above (elevated levels of lipid material in alveolar macrophages demonstrated by polychrome stain) and 3.3 mg/m(3) and above (increased

  11. TOXICITY OF TETRYL (N-METHYL-N,2,4,6-TETRANITROANILINE) IN F344 RATS

    EPA Science Inventory

    The toxicity of tetryl (N-methyl-N,2,4,6-tetranitroaniline) in male and female F344 rats was evaluated after adminstration in the diet for 14 or 90 days. The 14-day study diet concentrations used were 0, 500, 1250, 2000, 2500, and 5000 ppm; the 90-day study diet concentrations we...

  12. [Inhaled therapy in asthma].

    PubMed

    Plaza Moral, Vicente; Giner Donaire, Jordi

    2016-04-01

    Because of its advantages, inhaled administration of aerosolized drugs is the administration route of choice for the treatment of asthma and COPD. Numerous technological advances in the devices used in inhaled therapy in recent decades have boosted the appearance of multiple inhalers and aerosolized drugs. However, this variety also requires that the prescribing physician is aware of their characteristics. The main objective of the present review is to summarize the current state of knowledge on inhalers and inhaled drugs commonly used in the treatment of asthma. The review ranges from theoretical aspects (fundamentals and available devices and drugs) to practical and relevant aspects for asthma care in the clinical setting (therapeutic strategies, education, and adherence to inhalers).

  13. Inhalation Toxicity of Humidifier Disinfectants as a Risk Factor of Children’s Interstitial Lung Disease in Korea: A Case-Control Study

    PubMed Central

    Yu, Jinho; Lee, Eun; Jung, Young-Ho; Kim, Hyung-Young; Seo, Ju-Hee; Kwon, Geun-Yong; Park, Ji-Hyuk; Gwack, Jin; Youn, Seung-Ki; Kwon, Jun-Wook; Jun, Byung-Yool; Kim, Kyung Won; Ahn, Kangmo; Lee, Soo-Young; Park, June-Dong; Kwon, Ji-Won; Kim, Byoung-Ju; Lee, Moo-Song; Do, Kyung-Hyun; Jang, Se-Jin; Pyun, Bok-Yang; Hong, Soo-Jong

    2013-01-01

    Background The occurrence of numerous cases of interstitial lung disease in children (chILD) every spring in Korea starting in 2006 raised suspicion about a causal relationship with the use of humidifier disinfectants (HDs). The aim of this study was to evaluate the association between HD use and the risk of chILD. Methods This retrospective, 1∶3 matched case-control study consisted of 16 cases of chILD that had developed between 2010 and 2011. The three groups of parallel controls (patients with acute lobar pneumonia, asthma, and healthy children) were matched by age, gender, and index date. Indoor/outdoor environmental risk factors, including HD use, were investigated by asking the guardians to complete a questionnaire. Results The median age of the affected children (43.8% male) was 26 months (18.25–36.25). The chILD group did not differ significantly from the control groups with respect to socio-demographic and clinical variables. Indoor and outdoor environmental factors were not associated with a risk of chILD. However, the previous use of HDs (OR; 2.73. 95% CI; 1.41–5.90, P = 0.00) were independently associated with an increased risk. Conclusions This study showed that HDs, which are widely used in South Korea in the winter season, independently increased the risk of chILD in spring. Therefore, continuous monitoring and, if needed, changes in policy are essential to prevent and control pediatric diseases caused by toxic chemicals. PMID:23755124

  14. [New inhalation anesthetics].

    PubMed

    Conzen, P; Nuscheler, M

    1996-08-01

    Recently, two new halogenated volatile anaesthetics, sevoflurane and desflurane, have been approved for clinical use in Germany. Their low solubility in blood is the most important common property, and this represents the most obvious difference from the inhalational anaesthetics currently used. Extensive clinical and experimental evaluations have confirmed the superior pharmacokinetic properties predicted. Both sevoflurane and desflurane provide more rapid emergence from anaesthesia, permit easier titration of the anaesthetic dose during maintenance and offer more rapid recovery from anaesthesia. For sevoflurane, there are additional advantages: a pleasant odor, negligible airway irritation, and excellent pharmacodynamic characteristics that even provide cardiovascular stability comparable to isoflurane. A certain disadvantage and source of potential nephrotoxicity result from the metabolism of sevoflurane (2-5%) to anorganic fluoride and degradation to compound A in carbon dioxide absorbents. The extensive clinical data reported to date have revealed no evidence that sevoflurane has adverse renal effects. New insight into the pathomechanism of nephrotoxicity associated with either production of fluoride or compound A may well support clinical experience. Desflurane strongly resists in vivo metabolism and because of this it appears to be devoid of toxicity. Nevertheless, potential side-effects may result from degradation in dry absorbents and subsequent release of CO, from its extreme pungency and irritating airway effects. Thus, desflurane is not recommended for induction of anaesthesia, especially in children. The tendency for desflurane transiently to stimulate sympathetic activity, especially at concentrations above 1.0 MAC, limits its application in patients with cardiac disease.

  15. Toxicological Study No. 75-51-YJ81-93, 4-Amino-2-Nitrotoluene (4A2NT) Oral Approximate Lethal Dose 14-day Range Finding 90-Day Subchronic Feeding Studies in Rats, August 1991-November 1993

    DTIC Science & Technology

    1994-07-01

    NOVEMBER 1993 1. PURPOSE. The oral approximate lethal dose study was conducted todetennine an approximate dosage range at which to begin the 14-day...5000 mg/Kg. The 14-day range fmding study suggested a probable compound related effect in the薘~m (high dose ) exposure groups of both sexes and a...possible compound related effect mIlle 1000 ppm (middle dose ) exposure groups of both sexes. An NOAEL was not established for the 90-day subchronic

  16. Inhalant allergies in children.

    PubMed

    Mims, James W; Veling, Maria C

    2011-06-01

    Children with chronic or recurrent upper respiratory inflammatory disease (rhinitis) should be considered for inhalant allergies. Risk factors for inhalant allergies in children include a first-degree relative with allergies, food allergy in infancy, and atopic dermatitis. Although inhalant allergies are rare in infancy, inhalant allergies are common in older children and impair quality of life and productivity. Differentiating between viral and allergic rhinitis can be challenging in children, but the child's age, history, and risk factors can provide helpful information. Allergic rhinitis is a risk factor for asthma, and if one is present, medical consideration of the other is warranted.

  17. Inhalant Abuse and Dextromethorphan.

    PubMed

    Storck, Michael; Black, Laura; Liddell, Morgan

    2016-07-01

    Inhalant abuse is the intentional inhalation of a volatile substance for the purpose of achieving an altered mental state. As an important, yet underrecognized form of substance abuse, inhalant abuse crosses all demographic, ethnic, and socioeconomic boundaries, causing significant morbidity and mortality in school-aged and older children. This review presents current perspectives on epidemiology, detection, and clinical challenges of inhalant abuse and offers advice regarding the medical and mental health providers' roles in the prevention and management of this substance abuse problem. Also discussed is the misuse of a specific "over-the-counter" dissociative, dextromethorphan.

  18. Effects of inhaled manganese on biomarkers of oxidative stress in the rat brain.

    PubMed

    Taylor, Michael D; Erikson, Keith M; Dobson, Allison W; Fitsanakis, Vanessa A; Dorman, David C; Aschner, Michael

    2006-09-01

    Manganese (Mn) is a ubiquitous and essential element that can be toxic at high doses. In individuals exposed to high levels of this metal, Mn can accumulate in various brain regions, leading to neurotoxicity. In particular, Mn accumulation in the mid-brain structures, such as the globus pallidus and striatum, can lead to a Parkinson's-like movement disorder known as manganism. While the mechanism of this toxicity is currently unknown, it has been postulated that Mn may be involved in the generation of reactive oxygen species (ROS) through interaction with intracellular molecules, such as superoxide and hydrogen peroxide, produced within mitochondria. Conversely, Mn is a required component of an important antioxidant enzyme, Mn superoxide dismutase (MnSOD), while glutamine synthetase (GS), a Mn-containing astrocyte-specific enzyme, is exquisitely sensitive to oxidative stress. To investigate the possible role of oxidative stress in Mn-induced neurotoxicity, a series of inhalation studies was performed in neonatal and adult male and female rats as well as senescent male rats exposed to various levels of airborne-Mn for periods of time ranging from 14 to 90 days. Oxidative stress was then indirectly assessed by measuring glutathione (GSH), metallothionein (MT), and GS levels in several brain regions. MT and GS mRNA levels and regional brain Mn concentrations were also determined. The collective results of these studies argue against extensive involvement of ROS in Mn neurotoxicity in rats of differing genders and ages. There are, however, instances of changes in individual endpoints consistent with oxidative stress in certain brain tissues.

  19. Toxic hazards research unit

    SciTech Connect

    Macewen, J.D.; Vernot, E.H.

    1980-08-01

    Chronic toxicity or oncogenic studies were carried out with methylcyclohexane, tricyclodecane, purified 1,1-dimethylhydrazine, and bicycloheptadiene. A subchronic inhalation study was conducted with shale derived JP-5 and DFM fuels. Acute toxicity studies were conducted on a variety of chemical agents used by the Air Force and Navy.

  20. Modeling Deposition of Inhaled Particles

    EPA Science Inventory

    The mathematical modeling of the deposition and distribution of inhaled aerosols within human lungs is an invaluable tool in predicting both the health risks associated with inhaled environmental aerosols and the therapeutic dose delivered by inhaled pharmacological drugs. Howeve...

  1. Nonthermal Inhalation Injury.

    DTIC Science & Technology

    1992-01-01

    understand the effects of the various byproducts of combustion on the human body. A thorough knowledge of the physiological mechanisms , relevant...as soon as possible. Overview of Smoke Inhalation Physiology The physiologic mechanisms of injury from smoke inhalation are multiple and complex...to breathe Lower airway obstruction Dyspnea, tachypnea, wheezing, rhonchi, carbonaceous sputum Parenchymal injury Dyspnea, tachypnea, rales Table 1

  2. Other Priority Air Toxics in New England | Air Toxics | New ...

    EPA Pesticide Factsheets

    2017-04-10

    The air toxics of greatest concern in New England were selected due to risk modeling for only the inhalation route of exposure and these pollutants exceeded the health benchmarks in one or more of the New England states.

  3. Inhalants in Peru.

    PubMed

    Lerner, R; Ferrando, D

    1995-01-01

    In Peru, the prevalence and consequences of inhalant abuse appear to be low in the general population and high among marginalized children. Inhalant use ranks third in lifetime prevalence after alcohol and tobacco. Most of the use appears to be infrequent. Among marginalized children, that is, children working in the streets but living at home or children living in the street, the problem of inhalant abuse is a serious problem. Among children working in the streets but living at home, the lifetime prevalence rate for inhalant abuse is high, ranging from 15 to 45 percent depending on the study being cited. For children living in the streets, the use of inhalant is even more severe. As mentioned earlier in this chapter, most of these street children use inhalants on a daily basis. The lack of research on the problem of inhalant abuse is a serious impediment to development of intervention programs and strategies to address this problem in Peru. Epidemiologic and ethnographic research on the nature and extent of inhalant abuse are obvious prerequisites to targeted treatment and preventive intervention programs. The urgent need for current and valid data is underscored by the unique vulnerability of the youthful population at risk and the undisputed harm that results from chronic abuse of inhalants. Nonetheless, it is important to mention several programs that work with street children. Some, such as the Information and Education Center for the Prevention of Drug Abuse, Generation, and Centro Integracion de Menores en Abandono have shelters where street children are offered transition to a less marginal lifestyle. Teams of street educators provide the children with practical solutions and gain their confidence, as well as offer them alternative socialization experiences to help them survive the streets and avoid the often repressive and counterproductive environments typical of many institutions. Most of the children who go through these programs tend to abandon

  4. Antitubercular inhaled therapy: opportunities, progress and challenges.

    PubMed

    Pandey, Rajesh; Khuller, G K

    2005-04-01

    Pulmonary tuberculosis remains the commonest form of this disease and the development of methods for delivering antitubercular drugs directly to the lungs via the respiratory route is a rational therapeutic goal. The obvious advantages of inhaled therapy include direct drug delivery to the diseased organ, targeting to alveolar macrophages harbouring the mycobacteria, reduced risk of systemic toxicity and improved patient compliance. Research efforts have demonstrated the feasibility of various drug delivery systems employing liposomes, polymeric microparticles and nanoparticles to serve as inhalable antitubercular drug carriers. In particular, nanoparticles have emerged as a remarkably useful tool for this purpose. While some researchers have preferred dry powder inhalers, others have emphasized nebulization. Beginning with the respiratory delivery of a single antitubercular drug, it is now possible to deliver multiple drugs simultaneously with a greater therapeutic efficacy. More experience and expertise have been observed with synthetic polymers, nevertheless, the possibility of using natural polymers for inhaled therapy has yet to be explored. Several key issues such as patient education, cost of treatment, stability and large scale production of drug formulations, etc. need to be addressed before antitubercular inhaled therapy finds its way from theory to clinical reality.

  5. IRIS Toxicological Review of Formaldehyde (Inhalation) ...

    EPA Pesticide Factsheets

    UPDATE EPA is currently revising its Integrated Risk Information System (IRIS) assessment of formaldehyde to address the 2011 NAS peer review recommendations. This assessment addresses both noncancer and cancer human health effects that are relevant to assessing the risks from chronic inhalation exposure to formaldehyde. To facilitate discussion of several scientific issues pertinent to the assessment, EPA convened a state-of-the-science workshop on April 30 and May 1, 2014. This workshop focused on the following three themes: Evidence pertaining to the influence of formaldehyde that is produced endogenously (by the body during normal biological processes) on the toxicity of inhaled formaldehyde, and implications for the health assessment; Mechanistic evidence relevant to formaldehyde inhalation exposure and lymphohematopoietic cancers (leukemia and lymphomas); and Epidemiological research examining the potential association between formaldehyde exposure and lymphohematopoietic cancers (leukemia and lymphomas). June 2010: EPA is conducting an independent expert peer review by the National Academy of Sciences and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Formaldehyde-Inhalation that when finalized will appear on the Integrated Risk Information System (IRIS) database. This draft IRIS health assessment addresses both noncancer and cancer human health effects that may result from chronic inhal

  6. The Toxicity of Inhaled Sulphur Mustard

    DTIC Science & Technology

    2012-10-01

    BLANK UK UNCLASSIFIED Dstl/TR60201 Page 1 of 92 UK UNCLASSIFIED 1 Introduction The use of sulphur mustard (bis(2-chloroethyl) sulphide ; HD) as a... sulphide ; HD) as a chemical warfare (CW) agent remains of concern to the Armed Forces. Since its first use in World War 1 (WW1; Prentiss, 1937) HD has...Methyl- salicylate (MS); Minute Volume; Model Development; Pig; Porcine; Sulphur Mustard (HD) • Vapor; Bis(2-chloroethyl) sulphide INTRODUCTION Sulphur

  7. Chronic Inhalation Toxicity of Hydrazine: Oncogenic Effects

    DTIC Science & Technology

    1981-06-01

    suggesting that the loss was due to appetite suppression. Gross and microscopic examination of tissues from these animals taken at termination of the...97(85) 91/100(91) 83/97(86) 89/98(91) Myocardial fibrosis 49/147(33) 24/97(25) 24/100(24) 26/97(27) 23/98(23) Thymus: Regression 8S/147(58) 55/97(57...82/147(56) 34/97(35) 52/100(52) 54/97(56) 79/98(81)* Uterus: Polyps 26/147(18) 23/97(24) 21/100(21) 19/97(20) 19/98(19) Cystic endometrial hyperplasia

  8. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...: Electrolyte balance, carbohydrate metabolism, and liver and kidney function. The selection of specific tests.... (ii) At least the liver, kidneys, adrenals, brain, and gonads shall be weighed wet, as soon as... glands; liver; spleen; kidneys; adrenals; pancreas; gonads; uterus; accessory genital organs...

  9. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...: Electrolyte balance, carbohydrate metabolism, and liver and kidney function. The selection of specific tests.... (ii) At least the liver, kidneys, adrenals, brain, and gonads shall be weighed wet, as soon as... glands; liver; spleen; kidneys; adrenals; pancreas; gonads; uterus; accessory genital organs...

  10. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...: Electrolyte balance, carbohydrate metabolism, and liver and kidney function. The selection of specific tests.... (ii) At least the liver, kidneys, adrenals, brain, and gonads shall be weighed wet, as soon as... glands; liver; spleen; kidneys; adrenals; pancreas; gonads; uterus; accessory genital organs...

  11. Methods to Develop Inhalation Cancer Risk Estimates for ...

    EPA Pesticide Factsheets

    This document summarizes the approaches and rationale for the technical and scientific considerations used to derive inhalation cancer risks for emissions of chromium and nickel compounds from electric utility steam generating units. The purpose of this document is to discuss the methods used to develop inhalation cancer risk estimates associated with emissions of chromium and nickel compounds from coal- and oil-fired electric utility steam generating units (EGUs) in support of EPA's recently proposed Air Toxics Rule.

  12. Preliminary Assessment of the Relative Toxicity of 1,5-Diazido-3- Nitrazapentane 90-Day Dermal Application Male and Female Rabbits Study Number 75-51-Y809-90, May 1990 - June 1992. Phase 2

    DTIC Science & Technology

    1992-06-01

    blood samples were collected by the cephalic ear artery from both male and female rabbits each dose group. Tables 4 and 5 list the clinical chemistry and...4. CLINICAL CHEMISTRY Serum Glutamic Oxaloacetic Transaminase (SGOT) (AST) (Aspartate Aminotransferase) Serum Glutamic Pyruvic Transaminase (SGPT...Appendices C-L). (3) The clinical chemistry values (Appendices I and J) showed a significant change in total protein in the 78 mg/kg group for male rabbits and

  13. [Ventricular fibrillation following deodorant spray inhalation].

    PubMed

    Girard, F; Le Tacon, S; Maria, M; Pierrard, O; Monin, P

    2008-01-01

    We report one case of out-of-hospital cardiac arrest with ventricular fibrillation following butane poisoning after inhalation of antiperspiration aerosol. An early management using semi-automatic defibrillator explained the success of the resuscitation. The mechanism of butane toxicity could be an increased sensitivity of cardiac receptors to circulating catecholamines, responsible for cardiac arrest during exercise and for resuscitation difficulties. The indication of epinephrine is discussed.

  14. Budesonide Oral Inhalation

    MedlinePlus

    Budesonide is used to prevent difficulty breathing, chest tightness, wheezing, and coughing caused by asthma. Budesonide powder for oral inhalation (Pulmicort Flexhaler) is used in adults and children 6 ...

  15. Acetylcysteine Oral Inhalation

    MedlinePlus

    Acetylcysteine inhalation is used along with other treatments to relieve chest congestion due to thick or abnormal ... that causes problems with breathing, digestion, and reproduction). Acetylcysteine is in a class of medications called mucolytic ...

  16. Zanamivir Oral Inhalation

    MedlinePlus

    ... you use an inhaled medication to treat asthma, emphysema, or other breathing problems and you are scheduled ... the air passages that lead to the lungs); emphysema (damage to air sacs in the lungs); or ...

  17. Ipratropium Oral Inhalation

    MedlinePlus

    Ipratropium oral inhalation is used to prevent wheezing, shortness of breath, coughing, and chest tightness in people ... damage to the air sacs in the lungs). Ipratropium is in a class of medications called bronchodilators. ...

  18. Pirbuterol Acetate Oral Inhalation

    MedlinePlus

    ... mouth or throat irritation, rinse your mouth with water, chew gum, or suck sugarless hard candy after using pirbuterol.Inhalation devices require regular cleaning. Once a week, remove the mouthpiece cover, turn ...

  19. Umeclidinium Oral Inhalation

    MedlinePlus

    ... chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs ... Do not use umeclidinium inhalation during a sudden COPD attack. Your doctor will prescribe a short-acting ( ...

  20. Olodaterol Oral Inhalation

    MedlinePlus

    ... chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs ... Do not use olodaterol inhalation during a sudden COPD attack. Your doctor will prescribe a short-acting ( ...

  1. Comparison of growth, serum biochemistries and n-6 fatty acid metabolism in rats fed diets supplemented with high-gamma-linolenic acid safflower oil or borage oil for 90 days.

    PubMed

    Tso, Patrick; Caldwell, Jody; Lee, Dana; Boivin, Gregory P; DeMichele, Stephen J

    2012-06-01

    Recently, steps have been taken to further developments toward increasing gamma-linolenic acid (GLA) concentration and lowering costs in plant seed oils using transgenic technology. Through identification and expression of a fungal delta-6 desaturase gene in the high linoleic acid safflower plant, the seeds from this genetic transformation produce oil with >40% GLA (high GLA safflower oil (HGSO)). The aim of the study was to compare the effects of feeding HGSO to a generally recognized as safe source of GLA, borage oil, in a 90 day safety study in rats. Weanling male and female Sprague-Dawley rats were fed a semi-synthetic, fat free, pelleted diet (AIN93G) supplemented with a 10% (wt/wt) oil blend containing HGSO or borage oil, with equivalent GLA levels. Results demonstrated that feeding diets containing HGSO or borage oil for 90 days had similar biologic effects with regard to growth characteristics, body composition, behavior, organ weight and histology, and parameters of hematology and serum biochemistries in both sexes. Metabolism of the primary n-6 fatty acids in plasma and organ phospholipids was similar, despite minor changes in females. We conclude that HGSO is biologically equivalent to borage oil and provides a safe alternative source of GLA in the diet.

  2. Inhaled human insulin.

    PubMed

    Strack, Thomas R

    2006-04-01

    The benefit of subcutaneous insulin therapy in patients with diabetes is frequently limited due to difficulty in convincing patients of the importance of multiple daily insulin injections to cope effectively with meal-associated glycemic changes. Thus, the aim of achieving tight glycemic control, which is critical for reducing the risk of long-term diabetes-related complications, frequently remains elusive. The successful development of an inhalable insulin as a noninvasive alternative promises to change the management of diabetes. The first product to become available to patients is inhaled human insulin, a dry-powder formulation packaged into discrete blisters containing 1 or 3 mg of dry-powder human insulin and administered via a unique pulmonary inhaler device. It has recently been approved in both the United States and the European Union for the control of hyperglycemia in adult patients with type 1 or type 2 diabetes. The pharmacokinetic profile of inhaled human insulin closely mimics the natural pattern of insulin secretion, and resembles that of rapid-acting subcutaneous analogs. Similarly to rapid-acting subcutaneous analogs, inhaled human insulin has a more rapid onset of glucose-lowering activity compared to subcutaneous regular insulin, allowing it to be administered shortly before meals. It has a duration of glucose-lowering activity comparable to subcutaneous regular insulin and longer than rapid-acting insulin analogs. Inhaled human insulin effectively controls postprandial glucose concentrations in patients with type 1 or type 2 diabetes without increasing the risk of hypoglycemia, and even improves fasting glucose levels compared to subcutaneous insulin. Inhaled human insulin has an overall favorable safety profile. There are small reductions in lung function (1-1.5% of total lung forced expiratory volume in the first second [FEV1] capacity) after onset of treatment that are reversible in most patients if treatment is discontinued. Inhaled human

  3. Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90 days of exposure to hexavalent chromium in drinking water

    SciTech Connect

    Kopec, Anna K.; Kim, Suntae; Forgacs, Agnes L.; Zacharewski, Timothy R.; Proctor, Deborah M.; Harris, Mark A.; Haws, Laurie C.; Thompson, Chad M.

    2012-02-15

    Chronic administration of high doses of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) elicits alimentary cancers in mice. To further elucidate key events underlying tumor formation, a 90-day drinking water study was conducted in B6C3F1 mice. Differential gene expression was examined in duodenal and jejunal epithelial samples following 7 or 90 days of exposure to 0, 0.3, 4, 14, 60, 170 or 520 mg/L SDD in drinking water. Genome-wide microarray analyses identified 6562 duodenal and 4448 jejunal unique differentially expressed genes at day 8, and 4630 and 4845 unique changes, respectively, in the duodenum and jejunum at day 91. Comparative analysis identified significant overlap in duodenal and jejunal differential gene expression. Automated dose–response modeling identified > 80% of the differentially expressed genes exhibited sigmoidal dose–response curves with EC{sub 50} values ranging from 10 to 100 mg/L SDD. Only 16 genes satisfying the dose-dependent differential expression criteria had EC{sub 50} values < 10 mg/L SDD, 3 of which were regulated by Nrf2, suggesting oxidative stress in response to SDD at low concentrations. Analyses of differentially expressed genes identified over-represented functions associated with oxidative stress, cell cycle, lipid metabolism, and immune responses consistent with the reported effects on redox status and histopathology at corresponding SDD drinking water concentrations. Collectively, these data are consistent with a mode of action involving oxidative stress and cytotoxicity as early key events. This suggests that the tumorigenic effects of chronic Cr(VI) oral exposure likely require chronic tissue damage and compensatory epithelial cell proliferation. Highlights: ► Mouse small intestine gene expression is highly responsive to hexavalent chromium [Cr(VI)]. ► Cr(VI) elicits more differential gene expression after 7 days of exposure than 90 days of exposure. ► Oral exposure to Cr(VI) leads to

  4. Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90days of exposure to hexavalent chromium in drinking water.

    PubMed

    Kopec, Anna K; Kim, Suntae; Forgacs, Agnes L; Zacharewski, Timothy R; Proctor, Deborah M; Harris, Mark A; Haws, Laurie C; Thompson, Chad M

    2012-02-15

    Chronic administration of high doses of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) elicits alimentary cancers in mice. To further elucidate key events underlying tumor formation, a 90-day drinking water study was conducted in B6C3F1 mice. Differential gene expression was examined in duodenal and jejunal epithelial samples following 7 or 90days of exposure to 0, 0.3, 4, 14, 60, 170 or 520mg/L SDD in drinking water. Genome-wide microarray analyses identified 6562 duodenal and 4448 jejunal unique differentially expressed genes at day 8, and 4630 and 4845 unique changes, respectively, in the duodenum and jejunum at day 91. Comparative analysis identified significant overlap in duodenal and jejunal differential gene expression. Automated dose-response modeling identified >80% of the differentially expressed genes exhibited sigmoidal dose-response curves with EC(50) values ranging from 10 to 100mg/L SDD. Only 16 genes satisfying the dose-dependent differential expression criteria had EC(50) values <10mg/L SDD, 3 of which were regulated by Nrf2, suggesting oxidative stress in response to SDD at low concentrations. Analyses of differentially expressed genes identified over-represented functions associated with oxidative stress, cell cycle, lipid metabolism, and immune responses consistent with the reported effects on redox status and histopathology at corresponding SDD drinking water concentrations. Collectively, these data are consistent with a mode of action involving oxidative stress and cytotoxicity as early key events. This suggests that the tumorigenic effects of chronic Cr(VI) oral exposure likely require chronic tissue damage and compensatory epithelial cell proliferation.

  5. INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE (LA) AND AMOSITE ASBESTOS

    EPA Science Inventory

    Inhalation toxicology studies are being conducted to inform the risk assessment ofLibby amphibole. The overall purpose of these studies is to compare the toxicity of inhaled Libby amphibole fibers to a positive control fiber sample (UICC amosite). A 2-week study was conducted to ...

  6. Inhalation cancer risk assessment of cobalt metal.

    PubMed

    Suh, Mina; Thompson, Chad M; Brorby, Gregory P; Mittal, Liz; Proctor, Deborah M

    2016-08-01

    Cobalt compounds (metal, salts, hard metals, oxides, and alloys) are used widely in various industrial, medical and military applications. Chronic inhalation exposure to cobalt metal and cobalt sulfate has caused lung cancer in rats and mice, as well as systemic tumors in rats. Cobalt compounds are listed as probable or possible human carcinogens by some agencies, and there is a need for quantitative cancer toxicity criteria. The U.S. Environmental Protection Agency has derived a provisional inhalation unit risk (IUR) of 0.009 per μg/m(3) based on a chronic inhalation study of soluble cobalt sulfate heptahydrate; however, a recent 2-year cancer bioassay affords the opportunity to derive IURs specifically for cobalt metal. The mechanistic data support that the carcinogenic mode of action (MOA) is likely to involve oxidative stress, and thus, non-linear/threshold mechanisms. However, the lack of a detailed MOA and use of high, toxic exposure concentrations in the bioassay (≥1.25 mg/m(3)) preclude derivation of a reference concentration (RfC) protective of cancer. Several analyses resulted in an IUR of 0.003 per μg/m(3) for cobalt metal, which is ∼3-fold less potent than the provisional IUR. Future research should focus on establishing the exposure-response for key precursor events to improve cobalt metal risk assessment.

  7. Preclinical safety evaluation of inhaled cyclosporine in propylene glycol.

    PubMed

    Wang, Tao; Noonberg, Sarah; Steigerwalt, Ronald; Lynch, Maryellen; Kovelesky, Rosemary A; Rodríguez, Carlos A; Sprugel, Katherine; Turner, Nancy

    2007-01-01

    Cyclosporine inhalation solution has the potential to improve outcomes following lung transplantation by delivering high concentrations of an immunosuppressant directly to the allograft while minimizing systemic drug exposure and associated toxicity. The objective of these studies was to evaluate the potential toxicity of aerosolized cyclosporine formulated in propylene glycol when given by inhalation route to rats and dogs for 28 days. Sprague-Dawley rats received total inhaled doses of 0 (air), 0 (vehicle, propylene glycol), 7.4, 24.3, and 53.9 mg cyclosporine/kg/day. In a separate study, beagle dogs were exposed to 0, 4.4, 7.7, and 9.7 mg cyclosporine/kg/day. Endpoints used to evaluate potential toxicity of inhaled cyclosporine were clinical observations, body weight, food consumption, respiratory functions, toxicokinetics, and clinical/anatomic pathology. Daily administration of aerosolized cyclosporine did not result in observable accumulation of cyclosporine in blood or lung tissue. Toxicokinetic analysis from the rat study showed that the exposure of cyclosporine was approximately 18 times higher in the lung tissue compared to the blood. Systemic effects were consistent with those known for cyclosporine. There was no unexpected systemic toxicity or clinically limiting local respiratory toxicity associated with inhalation exposure to cyclosporine inhalation solution at exposures up to 2.7 times the maximum human exposure in either rats or dogs. There were no respiratory or systemic effects of high doses of propylene glycol relative to air controls. These preclinical studies demonstrate the safety of aerosolized cyclosporine in propylene glycol and support its continued clinical investigation in patients undergoing allogeneic lung transplantation.

  8. MODELING DEPOSITION OF INHALED PARTICLES

    EPA Science Inventory

    Modeling Deposition of Inhaled Particles: ABSTRACT

    The mathematical modeling of the deposition and distribution of inhaled aerosols within human lungs is an invaluable tool in predicting both the health risks associated with inhaled environmental aerosols and the therapeut...

  9. STIR Version 1.0 User's Guide for Pesticide Inhalation Risk

    EPA Pesticide Factsheets

    STIR estimates inhalation-type exposure based on pesticide-specific information. It also estimates spray droplet exposure using the application method and rate and then compares these exposure estimates to avian and mammalian toxicity data.

  10. NATIONAL-SCALE ASSESSMENT OF AIR TOXICS RISKS

    EPA Science Inventory

    The national-scale assessment of air toxics risks is a modeling assessment which combines emission inventory development, atmospheric fate and transport modeling, exposure modeling, and risk assessment to characterize the risk associated with inhaling air toxics from outdoor sour...

  11. Inhalants. Specialized Information Service.

    ERIC Educational Resources Information Center

    Do It Now Foundation, Phoenix, AZ.

    The document presents a collection of articles about inhalant abuse. Article 1 presents findings on the psychophysiological effects related to the use of amyl or butyl nitrate as a "recreational drug." Article 2 suggests a strong association between chronic sniffing of the solvent toulene and irreversible brain damage. Article 3 warns…

  12. Mercury vapor and female reproductive toxicity.

    PubMed

    Davis, B J; Price, H C; O'Connor, R W; Fernando, R; Rowland, A S; Morgan, D L

    2001-02-01

    Epidemiological studies finding menstrual cycle abnormalities among women occupationally exposed to Hg degrees prompted us to investigate the mechanisms of reproductive toxicity of Hg degrees in the female rat. Nose-only Hg degrees vapor inhalation exposures were conducted on regularly cycling rats 80-90 days of age in dose-response and acute time-course studies, which have previously proven useful as a model to identify ovarian toxicants. Vaginal smears were evaluated daily and serum hormone levels were correlated with cycle and with ovarian morphology at necropsy. Exposure concentration-related effects of Hg degrees were evaluated by exposing rats to 0, 1, 2, or 4 mg/m3 Hg degrees vapor 2 h/day for 11 consecutive days. Tissue Hg levels correlated with exposure concentration and duration. Exposure of rats to 4 mg/m3 (but not 1 or 2 mg/m3) Hg vapor for 11 days resulted in significant decreases in body weights relative to controls. Estrous cycles were slightly prolonged in the 2 and 4 mg/m3 dose groups, and serum estradiol and progesterone levels were significantly different in the 4 mg/m3 group compared to controls. The alterations in cycle and hormones at the 4 mg/m3 exposure concentration were attributed to body weight loss and generalized toxicity. In the time-course study, rats were exposed to 2 mg/m3 Hg degrees or air beginning in metestrus and evaluated daily for 8 days. A lengthening of the cycle was detected and morphological changes were observed in the corpora lutea (CL) after exposure for 6 days. To determine if changes in the CL and cyclicity correlated with a functional defect, rats were exposed to Hg degrees vapor and evaluated for pregnancy outcome. There were no significant effects on pregnancy rate or numbers of implantation sites when rats were exposed to 1 or 2 mg/m3 Hg degrees for 8 days prior to breeding, or when exposed for 8 days after breeding. These studies indicate that exposure to Hg degrees vapor altered estrous cyclicity, but had no

  13. Generation and characterization of aerosols and vapors for inhalation experiments.

    PubMed Central

    Tillery, M I; Wood, G O; Ettinger, H J

    1976-01-01

    Control of aerosol and vapor characteristics that affect the toxicity of inhaled contaminants often determines the methods of generating exposure atmospheres. Generation methods for aerosols and vapors are presented. The characteristics of the resulting exposure atmosphere and the limitations of the various generation methods are discussed. Methods and instruments for measuring the airborne contaminant with respect to various charcteristics are also described. PMID:797565

  14. Wildlife ecological screening levels for inhalation of volatile organic chemicals.

    PubMed

    Gallegos, Patricia; Lutz, Jill; Markwiese, James; Ryti, Randall; Mirenda, Rich

    2007-06-01

    For most chemicals, evaluation of ecological risk typically does not address inhalation because ingestion dominates exposure. However, burrowing ecological receptors have an increased exposure potential from inhalation at sites contaminated with volatile chemicals in the subsurface. Evaluation of ecological risk from contaminants like volatile organic chemicals (VOCs) is constrained by a lack of relevant ecological screening levels (ESLs). To address this need, inhalation ESLs were developed for 16 VOCs: Acetone, benzene, carbon tetrachloride, chloroform, chloromethane, dichlorodifluoromethane, 1,1-dichloroethane, 1,2-dichloroethane, 1,1-dichloroethene, methylene chloride, tetrachloroethene, toluene, 1,1,1-trichloroethane, trichloroethene, trichlorofluoromethane, and total xylene. These ESLs are based on Botta's pocket gopher (Thomomys bottae) as a representative fossorial receptor. The ESLs are presented with an emphasis on the process for developing inhalation toxicity reference values to illustrate the selection of suitable toxicity data and effect levels from the literature. The resulting ESLs provide a quantitative method for evaluating ecological risk of VOCs through comparison to relevant exposure data such as direct burrow-air measurements. The toxicity reference value development and ESL calculation processes and assumptions detailed here are provided as bases from which risk assessors can use or refine to suit site-specific needs with respect to toxicity and exposure inputs.

  15. Cardiomyopathy from 1,1-Difluoroethane Inhalation.

    PubMed

    Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

    2016-10-01

    Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.

  16. Food hypersensitivity by inhalation

    PubMed Central

    Ramirez, Daniel A; Bahna, Sami L

    2009-01-01

    Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization. PMID:19232116

  17. Treatment of Inhalation Injury

    DTIC Science & Technology

    1983-01-21

    injuries not visible with endoscopy. . Thermal and especially chemical inhalation injuries. Direct damage to the surfactant is probably implicated. o...exists a set of indirect alveolar lesions, subordinated to the skin burn itself, which is common in patients with extensive burns. This we call the...normo or hypocapnia. Very likely, a 5th lesional level exists which is the capillary itself(Venus et al). By primary or secondary damage , it affects the

  18. Inhalant abuse among adolescents: neurobiological considerations

    PubMed Central

    Lubman, D I; Yücel, M; Lawrence, A J

    2008-01-01

    Experimentation with volatile substances (inhalants) is common during early adolescence, yet limited work has been conducted examining the neurobiological impact of regular binge use during this key stage of development. Human studies consistently demonstrate that chronic use is associated with significant toxic effects, including neurological and neuropsychological impairment, as well as diffuse and subtle changes in white matter. However, most preclinical research has tended to focus on acute exposure, with limited work examining the neuropharmacological or toxicological mechanisms underpinning these changes or their potential reversibility with abstinence. Nevertheless, there is growing evidence that commonly abused inhalants share common cellular mechanisms, and have similar actions to other drugs of abuse. Indeed, the majority of acute behavioural effects appear to be underpinned by changes in receptor and/or ion channel activity (for example, GABAA, glycine and 5HT3 receptor activation, NMDA receptor inhibition), although nonspecific interactions can also arise at high concentrations. Recent studies examining the effects of toluene exposure during the early postnatal period are suggestive of long-term alterations in the function of NMDA and GABAA receptors, although limited work has been conducted investigating exposure during adolescence. Given the critical role of neurotransmitter systems in cognitive, emotional and brain development, future studies will need to take account of the substantial neuromaturational changes that are known to occur in the brain during childhood and adolescence, and to specifically investigate the neuropharmacological and toxicological profile of inhalant exposure during this period of development. PMID:18332858

  19. Blood Gases as an Indicator of Inhalation Injury and Prognosis in Burn Patients

    PubMed Central

    Megahed, M.A.; Ghareeb, F.; Kishk, T.; El-Barah, A.; Abou-Gereda, H.; El-Fol, H.; El-Sisy, A.; Omran, A.M.

    2008-01-01

    Summary Inhalation injury greatly increases the incidence of respiratory failure and the acute respiratory distress syndrome. It is also the cause of most early deaths in burn victims. The aim of our research was to study the incidence, early diagnosis, complications, and management of inhalation injury and to discuss the relation between inhalation injury and death in burn patients.This study included 130 burn patients with inhalation injury admitted to Menoufiya University Hospital Burn Center, Egypt, from January 2004 to April 2008 (61 males and 69 females). We found that the presence of inhalation injury, increasing burn size, and advancing age were all associated with increased mortality (p < 0.01). The incidence of inhalation injury in our study was 46.3% (130 patients were identified as having inhalation injury out of 281). The overall mortality for patients with inhalation injury was 41.5% (54 patients out of 130) compared with 7.2% (11 patients out of 151) for patients without inhalation injury. These statistical data make it clear that inhalation injury is an important factor for the prediction of mortality in burn patients. Approximately 80% of fire-related deaths are due not to the burn injury to the airway but to the inhalation of toxic products, especially carbon monoxide and hydrogen cyanide gases. Inhalation injury is generally caused by thermal burns, mostly confined to the upper airways.Major airway, pulmonary, and systemic complications may occur in cases of inhalation injury and thus increase the incidence of burn patient mortality PMID:21991136

  20. Inhalant-Abuse Myocarditis Diagnosed by Cardiac Magnetic Resonance

    PubMed Central

    Rao, Krishnasree; Matulevicius, Susan

    2016-01-01

    Multiple reports of toxic myocarditis from inhalant abuse have been reported. We now report the case of a 23-year-old man found to have toxic myocarditis from inhalation of a hydrocarbon. The diagnosis was made by means of cardiac magnetic resonance imaging with delayed enhancement. The use of cardiac magnetic resonance to diagnose myocarditis has become increasingly common in clinical medicine, although there is not a universally accepted criterion for diagnosis. We appear to be the first to document a case of toxic myocarditis diagnosed by cardiac magnetic resonance. In patients with a history of drug abuse who present with clinical findings that suggest myocarditis or pericarditis, cardiac magnetic resonance can be considered to support the diagnosis. PMID:27303242

  1. Cyanide poisoning by fire smoke inhalation: a European expert consensus.

    PubMed

    Anseeuw, Kurt; Delvau, Nicolas; Burillo-Putze, Guillermo; De Iaco, Fabio; Geldner, Götz; Holmström, Peter; Lambert, Yves; Sabbe, Marc

    2013-02-01

    Smoke inhalation is a common cause of cyanide poisoning during fires, resulting in injury and even death. In many cases of smoke inhalation, cyanide has increasingly been recognized as a significant toxicant. The diagnosis of cyanide poisoning remains very difficult, and failure to recognize it may result in inadequate or inappropriate treatment. Findings suggesting cyanide toxicity include the following: (a) a history of enclosed-space fire; (b) any alteration in the level of consciousness; (c) any cardiovascular changes (particularly inexplicable hypotension); and (d) elevated plasma lactate. The feasibility and safety of empiric treatment with hydroxocobalamin for fire smoke victims have been reported in the literature. On the basis of a literature review and a panel discussion, a group of European experts has proposed emergency management protocols for cyanide toxicity in fire smoke victims.

  2. Evaluation of two different metabolic hypotheses for dichloromethane toxicity using physiologically based pharmacokinetic (PBPK) modeling for in vivo inhalation gas uptake data exposure in female B6C3F1 mice *

    EPA Science Inventory

    Dichloromethane (DCM, methylene chloride) is a lipophilic volatile compound readily absorbed and then metabolized to several metabolites that may lead to chronic toxicity in different target organs. Physiologically based pharmacokinetic (PBPK) models are useful tools used for cal...

  3. Toxicity test of a dental commercial composite

    PubMed Central

    Ponce-Bravo, Santa; Martínez-Rivera, José-Luis; Garcés-Ortíz, Maricela

    2015-01-01

    Background International rules must be followed for testing biosecurity in dental materials. A new brand of restorative material appeared in the market and regulations indicated that it should be tested for toxicity. Objectives The aim of this study was to determine the 90-day sub chronic toxicity of one triethylene glycol dimethacrylate containing composite (MEDENTAL Light-Cure Composite™) orally administered to rats according to Organization for Economic Co-Operation and Development no. 48 guidelines and the requirements specified in the ISO 10993-11. Material and Methods Wistar rats ate the polymerized composite during 90 days and were observed to determine changes in their behavior, eye and skin signs and other attitudes such as aggressiveness, posture, walking and response to handling. After 90 days were sacrificed to ascertain blood alterations, we did special hematological tests and assessed microscopic slides from 33 different organs. Results We recorded no significant changes in clinical behavior of the animals. Microscopic review of the H&E stained slides obtained from the analyzed organs showed no abnormal inflammatory or cytological changes and all hematological special tests were within normal limits. Conclusions Results of this study show that under our experimental conditions the MEDENTAL Light-Cure Composite™ does not produce inflammatory or cytological changes suggestive of toxicity. Key words:Dental materials, composite resin, toxicity, inflammation, TEGDMA. PMID:26155348

  4. How to Use Metered-Dose Inhalers

    MedlinePlus

    ... inhaler the right way so that the full dose of medication reaches your lungs. You can use ... inhaler.These directions explain how to use metered-dose inhalers. If you are using a different type ...

  5. Health effects of inhaled gasoline engine emissions.

    PubMed

    McDonald, Jacob D; Reed, Matthew D; Campen, Matthew J; Barrett, Edward G; Seagrave, JeanClare; Mauderly, Joe L

    2007-01-01

    Despite their prevalence in the environment, and the myriad studies that have shown associations between morbidity or mortality with proximity to roadways (proxy for motor vehicle exposures), relatively little is known about the toxicity of gasoline engine emissions (GEE). We review the studies conducted on GEE to date, and summarize the findings from each of these studies. While there have been several studies, most of the studies were conducted prior to 1980 and thus were not conducted with contemporary engines, fuels, and driving cycles. In addition, many of the biological assays conducted during those studies did not include many of the assays that are conducted on contemporary inhalation exposures to air pollutants, including cardiovascular responses and others. None of the exposures from these earlier studies were characterized at the level of detail that would be considered adequate today. A recent GEE study was conducted as part of the National Environmental Respiratory Center (www.nercenter.org). In this study several in-use mid-mileage General Motors (Chevrolet S-10) vehicles were purchased and utilized for inhalation exposures. An exposure protocol was developed where engines were operated with a repeating California Unified Driving Cycle with one cold start per day. Two separate engines were used to provide two cold starts over a 6-h inhalation period. The exposure atmospheres were characterized in detail, including detailed chemical and physical analysis of the gas, vapor, and particle phase. Multiple rodent biological models were studied, including general toxicity and inflammation (e.g., serum chemistry, lung lavage cell counts/differentials, cytokine/chemokine analysis, histopathology), asthma (adult and in utero exposures with pulmonary function and biochemical analysis), cardiovascular effects (biochemical and electrocardiograph changes in susceptible rodent models), and susceptibility to infection (Pseudomonas bacteria challenge). GEE resulted in

  6. Inhalation exposure of animals.

    PubMed Central

    Phalen, R F

    1976-01-01

    Relative advantages and disadvantages and important design criteria for various exposure methods are presented. Five types of exposures are discussed: whole-body chambers, head-only exposures, nose or mouth-only methods, lung-only exposures, and partial-lung exposures. Design considerations covered include: air cleaning and conditioning; construction materials; losses of exposure materials; evenness of exposure; sampling biases; animal observation and care; noise and vibration control, safe exhausts, chamber loading, reliability, pressure fluctuations; neck seals, masks, animal restraint methods; and animal comfort. Ethical considerations in use of animals in inhalation experiments are also discussed. PMID:1017420

  7. Inhalation Lung Injury Associated with Humidifier Disinfectants in Adults

    PubMed Central

    2016-01-01

    We recently established a novel disease entity presented as progressive respiratory failure associated with the inhalation of humidifier disinfectants. In April 2011, we encountered a series of peripartum patients with complaints of respiratory distress of unknown etiology, which was an uncommon phenomenon. Accordingly, we created a multidisciplinary team comprising intensivists, radiologists, pathologists, epidemiologists, and the Korea Centers for Disease Control and Prevention (KCDC). Further, we defined the disease entity and performed a case-control study, epidemiologic investigation, and animal study to determine the etiology. The study findings indicated that the lung injury outbreak was related to the inhalation of humidifier disinfectants and showed that household chemical inhalation can cause severe respiratory failure. Following the withdrawal of humidifier disinfectants from the Korean market in 2012, no such cases were reported. This tragic event is a warning that appropriate safety regulations and monitoring for potential toxic household chemicals are critical to protect public health. PMID:27822921

  8. Inhalation delivery of protein therapeutics.

    PubMed

    Kane, Colleen; O'Neil, Karyn; Conk, Michelle; Picha, Kristen

    2013-04-01

    Inhaled therapeutics are used routinely to treat a variety of pulmonary diseases including asthma, COPD and cystic fibrosis. In addition, biological therapies represent the fastest growing segment of approved pharmaceuticals. However, despite the increased availability of biological therapies, nearly all inhaled therapeutics are small molecule drugs with only a single inhaled protein therapeutic approved. There remains a significant unmet need for therapeutics in pulmonary diseases, and biological therapies with potential to alter disease progression represent a significant opportunity to treat these challenging diseases. This review provides a background into efforts to develop inhaled biological therapies and highlights some of the associated challenges. In addition, we speculate on the ideal properties of a biologic therapy for inhaled delivery.

  9. Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor

    SciTech Connect

    Clewell, H.J. Efremenko, A.; Campbell, J.L.; Dodd, D.E.; Thomas, R.S.

    2014-10-01

    Male and female Fischer 344 rats were exposed to naphthalene vapors at 0 (controls), 0.1, 1, 10, and 30 ppm for 6 h/d, 5 d/wk, over a 90-day period. Following exposure, the respiratory epithelium and olfactory epithelium from the nasal cavity were dissected separately, RNA was isolated, and gene expression microarray analysis was conducted. Only a few significant gene expression changes were observed in the olfactory or respiratory epithelium of either gender at the lowest concentration (0.1 ppm). At the 1.0 ppm concentration there was limited evidence of an oxidative stress response in the respiratory epithelium, but not in the olfactory epithelium. In contrast, a large number of significantly enriched cellular pathway responses were observed in both tissues at the two highest concentrations (10 and 30 ppm, which correspond to tumorigenic concentrations in the NTP bioassay). The nature of these responses supports a mode of action involving oxidative stress, inflammation and proliferation. These results are consistent with a dose-dependent transition in the mode of action for naphthalene toxicity/carcinogenicity between 1.0 and 10 ppm in the rat. In the female olfactory epithelium (the gender/site with the highest incidences of neuroblastomas in the NTP bioassay), the lowest concentration at which any signaling pathway was significantly affected, as characterized by the median pathway benchmark dose (BMD) or its 95% lower bound (BMDL) was 6.0 or 3.7 ppm, respectively, while the lowest female olfactory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 16.1, 11.1, and 8.4 ppm, respectively. In the male respiratory epithelium (the gender/site with the highest incidences of adenomas in the NTP bioassay), the lowest pathway BMD and BMDL were 0.4 and 0.3 ppm, respectively, and the lowest male respiratory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 0.5, 0.7, and 0.9 ppm

  10. Exubera. Inhale therapeutic systems.

    PubMed

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  11. Inhaled Antibiotics for Gram-Negative Respiratory Infections.

    PubMed

    Wenzler, Eric; Fraidenburg, Dustin R; Scardina, Tonya; Danziger, Larry H

    2016-07-01

    Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena.

  12. Cherry-flavoured electronic cigarettes expose users to the inhalation irritant, benzaldehyde.

    PubMed

    Kosmider, Leon; Sobczak, Andrzej; Prokopowicz, Adam; Kurek, Jolanta; Zaciera, Marzena; Knysak, Jakub; Smith, Danielle; Goniewicz, Maciej L

    2016-04-01

    Many non-cigarette tobacco products, including e-cigarettes, contain various flavourings, such as fruit flavours. Although many flavourings used in e-cigarettes are generally recognised as safe when used in food products, concerns have been raised about the potential inhalation toxicity of these chemicals. Benzaldehyde, which is a key ingredient in natural fruit flavours, has been shown to cause irritation of respiratory airways in animal and occupational exposure studies. Given the potential inhalation toxicity of this compound, we measured benzaldehyde in aerosol generated in a laboratory setting from flavoured e-cigarettes purchased online and detected benzaldehyde in 108 out of 145 products. The highest levels of benzaldehyde were detected in cherry-flavoured products. The benzaldehyde doses inhaled with 30 puffs from flavoured e-cigarettes were often higher than doses inhaled from a conventional cigarette. Levels in cherry-flavoured products were >1000 times lower than doses inhaled in the workplace. While e-cigarettes seem to be a promising harm reduction tool for smokers, findings indicate that using these products could result in repeated inhalation of benzaldehyde, with long-term users risking regular exposure to the substance. Given the uncertainty surrounding adverse health effects stemming from long-term inhalation of flavouring ingredients such as benzaldehyde, clinicians need to be aware of this emerging risk and ask their patients about use of flavoured e-cigarettes.

  13. Coal tar creosote abuse by vapour inhalation presenting with renal impairment and neurotoxicity: a case report.

    PubMed

    Hiemstra, Thomas F; Bellamy, Christopher Oc; Hughes, Jeremy H

    2007-09-24

    A 56 year old aromatherapist presented with advanced renal failure following chronic coal tar creosote vapour inhalation, and a chronic tubulo-interstitial nephritis was identified on renal biopsy. Following dialysis dependence occult inhalation continued, resulting in seizures, ataxia, cognitive impairment and marked generalised cerebral atrophy. We describe for the first time a case of creosote abuse by chronic vapour inhalation, resulting in significant morbidity. Use of the polycyclic aromatic hydrocarbon-containing wood preservative coal tar creosote is restricted by many countries due to concerns over environmental contamination and carcinogenicity. This case demonstrates additional toxicities not previously reported with coal tar creosote, and emphasizes the health risks of polycyclic aromatic hydrocarbon exposure.

  14. Deterioration in brain and heart functions following a single sub-lethal (0.8 LCt50) inhalation exposure of rats to sarin vapor: a putative mechanism of the long term toxicity.

    PubMed

    Allon, N; Chapman, S; Egoz, I; Rabinovitz, I; Kapon, J; Weissman, B A; Yacov, G; Bloch-Shilderman, E; Grauer, E

    2011-05-15

    The main injuries among victims of the terrorist act in the Tokyo subway resulted from sub-lethal inhalation and whole body exposure to sarin vapor. In order to study the long term effects of such exposure and to simulate these conditions, freely moving rats were exposed to sarin vapor (27.2±1.7 μg/l) for 10 min. About 50% of the rats showed no overt symptoms and the rest had mild to moderate clinical symptoms that subsided within 4h following exposure. A reduction of weight was noted during the first 3 days with full recovery on the 4th day. Rat's heart was challenged with epinephrine 1 and 6 months post exposure. A significant reduction in the threshold for epinephrine-induced arrhythmia (EPIA) was noted in rats exposed to sarin. A time dependent increase in the kD and Bmax values of muscarinic auto receptors (M2) was recorded in the rat's cortex and striatum. No changes were recorded in the rats' brain trans locator protein (TSPO) levels, concomitant with no observed changes in the animals' performance in A Morris water maze test. A significant increase in open field activity was noted 6 months following exposure to sarin vapor as well as a significant decrease in prostaglandin E₂ (PGE₂) production in the brain. It is speculated that down regulation of the M2 auto receptor function, caused hyper reactivity of the cholinergic system which leads to the changes described above. The continuous reduction in M2 auto-receptor system through an unknown mechanism may be the cause for long lasting decline in sarin-exposed casualties' health.

  15. Deposition, retention, and clearance of inhaled particles.

    PubMed Central

    Lippmann, M; Yeates, D B; Albert, R E

    1980-01-01

    The relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles greater than or equal to 2 micrometers that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from

  16. Umeclidinium and Vilanterol Oral Inhalation

    MedlinePlus

    ... chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs ... use umeclidinium and vilanterol inhalation during a sudden COPD attack. Your doctor will prescribe a short-acting ( ...

  17. Fluticasone and Vilanterol Oral Inhalation

    MedlinePlus

    ... and chest tightness caused by chronic obstructive pulmonary (COPD; a group of diseases that affect the lungs ... use fluticasone and vilanterol inhalation during a sudden COPD attack. Your doctor will prescribe a short acting ( ...

  18. Fluticasone and Salmeterol Oral Inhalation

    MedlinePlus

    ... caused by asthma and chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic ... and salmeterol during an attack of asthma or COPD. Your doctor will prescribe a short-acting inhaler ...

  19. [Inhaled antibiotic therapy in cystic fibrosis].

    PubMed

    Girón Moreno, Rosa M; Salcedo Posadas, Antonio; Mar Gómez-Punter, Rosa

    2011-06-01

    Cystic fibrosis is the most frequent fatal genetically-transmitted disease among Caucasians. Chronic bronchial infection, especially by Pseudomonas aeruginosa, is the main cause of morbidity and mortality in this disease. Aerosolized antibiotic therapy achieves high drug concentrations in the airway with low toxicity, allowing chronic use. Currently, two antibiotics have been approved for inhalation therapy, tobramycin inhalation solution and colistimethate sodium aerosol. There is less evidence from clinical trials for the latter. The main indication for these drugs is chronic bronchial colonization by P. aeruginosa, although there is increasing evidence of the importance of the primary infection by this bacterium, whether treated by oral or intravenous antibiotics or not. More controversial is the use of aerosolized antibiotic therapy in bacterial prophylaxis or respiratory exacerbations. For many years, intravenous formulations of distinct antibiotics for aerosolized use have been employed, which are in distinct phases of research for use in nebulizer therapy. In addition to being used to treat P. aeruginosa infection, aerosolized antibiotics have been used to treat other pathogens such as methicillin-resistant Staphylococus aureus, Mycobacterium abscessus and Aspergillus fumigatus.

  20. Potent Inhalational Anesthetics for Dentistry

    PubMed Central

    Satuito, Mary; Tom, James

    2016-01-01

    Nitrous oxide and the volatile inhalational anesthetics have defined anxiety and pain control in both dentistry and medicine for over a century. From curious experimentation to spectacular public demonstrations, the initial work of 2 dentists, Horace Wells and William T. G. Morton, persists to this day in modern surgery and anesthesia. This article reviews the history, similarities, differences, and clinical applications of the most popular inhalational agents used in contemporary dental surgical settings. PMID:26866411

  1. Inhaler Technique in Asthma: How Does It Relate to Patients' Preferences and Attitudes Toward Their Inhalers?

    PubMed Central

    Jahedi, Lia; Downie, Sue R.; Saini, Bandana; Chan, Hak-Kim

    2017-01-01

    Abstract Background: Correct inhaler technique can increase medication efficacy, reducing both dose and side effects. Patient preference for inhaler device has not been fully explored, and we hypothesized that if patients have a preference and can choose their inhaler, they might be more likely to use it correctly. Our aim was to determine the preferences, attitudes, and perceptions of patients with asthma toward their inhalers, and to evaluate whether any of these factors were related to inhalation technique. Methods: Twenty-five patients with asthma (mean age 43.1 years) participated. Qualitative semi-structured interviews and quantitative patient satisfaction and preference questionnaires (PASAPQ) were used to explore patients' preferences, attitudes, and perceptions about their inhalers. Objective inhalation technique assessment was performed. Data were triangulated to identify characteristics that could indicate a relationship between inhaler technique, satisfaction, preference, and decision making. Results: Themes from qualitative interviews were as follows: asthma inhalers and expectations; inhaler preference; characteristics of an ideal inhaler; perceived effectiveness of inhalers; and inhalers and patient decision making. PASAPQ scores indicated that all patients were at least “somewhat satisfied” with their inhalers, regardless of technique. Only 12% of inhalers were used correctly, despite pilot PASAPQ data suggesting that most patients were confident with their technique. The inhaler technique was unlikely to be related to satisfaction, perception of inhaler devices, or choice in device selection. Patients with correct inhaler technique were more aware of their asthma and expressed motivation to achieve optimal asthma control. Conclusions: The majority of the asthmatic patients did not use their inhaler(s) correctly, despite most having confidence in their technique. Patients attributed confidence in their inhaler technique to their belief that

  2. Inhalation a significant exposure route for chlorinated organophosphate flame retardants.

    PubMed

    Schreder, Erika D; Uding, Nancy; La Guardia, Mark J

    2016-05-01

    Chlorinated organophosphate flame retardants (ClOPFRs) are widely used as additive flame retardants in consumer products including furniture, children's products, building materials, and textiles. Tests of indoor media in homes, offices, and other environments have shown these compounds are released from products and have become ubiquitous indoor pollutants. In house dust samples from Washington State, U.S.A., ClOPFRs were the flame retardants detected in the highest concentrations. Two ClOPFRs, tris(1,3-dichloro-2-propyl)phosphate (TDCPP or TDCIPP) and tris(2-chloroethyl)phosphate (TCEP), have been designated as carcinogens, and there is growing concern about the toxicity of the homologue tris(1-chloro-2-propyl)phosphate (TCPP or TCIPP). In response to concerns about exposure to these compounds, the European Union and a number of U.S. states have taken regulatory action to restrict their use in certain product categories. To better characterize exposure to ClOPFRs, inhalation exposure was assessed using active personal air samplers in Washington State with both respirable and inhalable particulate fractions collected to assess the likelihood particles penetrate deep into the lungs. Concentrations of ∑ClOPFRs (respirable and inhalable) ranged from 97.1 to 1190 ng m(-3) (mean 426 ng m(-3)), with TCPP detected at the highest concentrations. In general, higher levels were detected in the inhalable particulate fraction. Total intake of ClOPFRs via the inhalation exposure route was estimated to exceed intake via dust ingestion, indicating that inhalation is an important route that should be taken into consideration in assessments of these compounds.

  3. Inhalation of titanium dioxide induces endoplasmic reticulum stress-mediated autophagy and inflammation in mice.

    PubMed

    Yu, Kyeong-Nam; Sung, Jae Hyuck; Lee, Somin; Kim, Ji-Eun; Kim, Sanghwa; Cho, Won-Young; Lee, Ah Young; Park, Soo Jin; Lim, Joohyun; Park, Changhoon; Chae, Chanhee; Lee, Jin Kyu; Lee, Jinkyu; Kim, Jun-Sung; Cho, Myung-Haing

    2015-11-01

    Titanium dioxide (TiO2) nanoparticles are widely used in cosmetics, sunscreen, electronics, drug delivery systems, and diverse bio-application fields. In the workplace, the primary exposure route for TiO2 nanoparticles is inhalation through the respiratory system. Because TiO2 nanoparticles have different physiological properties, in terms of size and bioactivity, their toxic effects in the respiratory system must be determined. In this study, to determine the toxic effect of inhaled TiO2 nanoparticles in the lung and the underlying mechanism, we used a whole-body chamber inhalation system to expose A/J mice to TiO2 nanoparticles for 28 days. During the experiments, the inhaled TiO2 nanoparticles were characterized using a cascade impactor and transmission electron microscopy. After inhalation of the TiO2 nanoparticles, hyperplasia and inflammation were observed in a TiO2 dose-dependent manner. To determine the biological mechanism of the toxic response in the lung, we examined endoplasmic reticulum (ER) and mitochondria in lung. The ER and mitochondria were disrupted and dysfunctional in the TiO2-exposed lung leading to abnormal autophagy. In summary, we assessed the potential risk of TiO2 nanoparticles in the respiratory system, which contributed to our understanding of the mechanism underlining TiO2 nanoparticle toxicity in the lung.

  4. Pneumoconiosis after sericite inhalation

    PubMed Central

    Algranti, E; Handar, A; Dumortier, P; Mendonca, E; Rodrigues, G; Santos, A; Mauad, T; Dolhnikoff, M; De Vuyst, P; Saldiva, P; Bussacos, M

    2005-01-01

    Aims: To investigate and describe the radiological, clinical, and pathological changes in miners and millers exposed to sericite dust with mineralogical characteristics of inhaled dust. Methods: The working premises were visited to examine the sericite processing and to classify the jobs according to make qualitative evaluation. Respirable dust was collected and the amount of crystalline silica and particle size distribution were measured. Forty four workers were examined by a standard questionnaire for respiratory symptoms, spirometry, and chest x ray. Material from an open lung biopsy was reviewed for histopathological and mineralogical analysis, together with sericite samples from the work site to compare the mineral characteristics in lung lesions and work area. Results: Respirable dust contained 4.5–10.0% crystalline silica. Particle size distribution showed a heavy burden of very fine particles (23–55%) with a mean diameter of <0.5 µm. Mean age of sericite miners was 41.0 (11.9) and mean number of years of exposure was 13.5 (10.1). In 52.3% of workers (23/44), chest radiographs presented a median category of 1/0 or above, and 18.2% (8/44) had a reduced FEV1. There was a significant association between exposure indices and x ray category. Histological studies of the lung biopsy showed lesions compatible with mixed dust fibrosis with no silicotic nodules. x Ray diffraction analysis of the lung dust residue and the bulk samples collected from work area showed similar mineralogical characteristics. Muscovite and kaolinite were the major mineral particle inclusions in the lung. Conclusion: Exposure to fine sericite particles is associated with the development of functional and radiological changes in workers inducing mixed dust lesions, which are distinct histologically from silicosis. PMID:15723874

  5. Nanotechnology-based inhalation treatments for lung cancer: state of the art

    PubMed Central

    Ahmad, Javed; Akhter, Sohail; Rizwanullah, Md; Amin, Saima; Rahman, Mahfoozur; Ahmad, Mohammad Zaki; Rizvi, Moshahid Alam; Kamal, Mohammad A; Ahmad, Farhan Jalees

    2015-01-01

    Considering the challenges associated with conventional chemotherapy, targeted and local delivery of chemotherapeutics via nanoparticle (NP) carriers to the lungs is an emerging area of interest. Recent studies and growing clinical application in cancer nanotechnology showed the huge potential of NPs as drug carriers in cancer therapy, including in lung carcinoma for diagnosis, imaging, and theranostics. Researchers have confirmed that nanotechnology-based inhalation chemotherapy is viable and more effective than conventional chemotherapy, with lesser side effects. Recently, many nanocarriers have been investigated, including liposomes, polymeric micelles, polymeric NPs, solid lipid NPs, and inorganic NPs for inhalation treatments of lung cancer. Yet, the toxicity of such nanomaterials to the lungs tissues and further distribution to other organs due to systemic absorption on inhalation delivery is a debatable concern. Here, prospect of NPs-based local lung cancer targeting through inhalation route as well as its associated challenges are discussed. PMID:26640374

  6. Toxic Hazards Research Unit annual technical report, 1972

    NASA Technical Reports Server (NTRS)

    Macewen, J. D.; Vernot, E. H.

    1972-01-01

    The activities of the Toxic Hazards Research Unit (THRU) for the period of June 1971 through May 1972 are reviewed in this report. Acute inhalation toxicity experiments were conducted on hydrogen chloride (HCl) gas and aerosol, ethyl bromide (C2H5Br), hydrogen bromide (HBr), hydrogen sulfide (H2S), ammonia (NH3), chlorine (CL2), and silane (SiH4). Subacute toxicity studies were conducted on chlorine pentafluoride (ClF5), dichloromethane (CH2Cl2) and coal tar volatiles. Further toxicity studies of subacute and chronic responses to inhaled monomethylhydrazine (MMH) are also described.

  7. Hazard identification of inhaled nanomaterials: making use of short-term inhalation studies.

    PubMed

    Klein, Christoph L; Wiench, Karin; Wiemann, Martin; Ma-Hock, Lan; van Ravenzwaay, Ben; Landsiedel, Robert

    2012-07-01

    A major health concern for nanomaterials is their potential toxic effect after inhalation of dusts. Correspondingly, the core element of tier 1 in the currently proposed integrated testing strategy (ITS) is a short-term rat inhalation study (STIS) for this route of exposure. STIS comprises a comprehensive scheme of biological effects and marker determination in order to generate appropriate information on early key elements of pathogenesis, such as inflammatory reactions in the lung and indications of effects in other organs. Within the STIS information on the persistence, progression and/or regression of effects is obtained. The STIS also addresses organ burden in the lung and potential translocation to other tissues. Up to now, STIS was performed in research projects and routine testing of nanomaterials. Meanwhile, rat STIS results for more than 20 nanomaterials are available including the representative nanomaterials listed by the Organization for Economic Cooperation and Development (OECD) working party on manufactured nanomaterials (WPMN), which has endorsed a list of representative manufactured nanomaterials (MN) as well as a set of relevant endpoints to be addressed. Here, results of STIS carried out with different nanomaterials are discussed as case studies. The ranking of different nanomaterials potential to induce adverse effects and the ranking of the respective NOAEC are the same among the STIS and the corresponding subchronic and chronic studies. In another case study, a translocation of a coated silica nanomaterial was judged critical for its safety assessment. Thus, STIS enables application of the proposed ITS, as long as reliable and relevant in vitro methods for the tier 1 testing are still missing. Compared to traditional subacute and subchronic inhalation testing (according to OECD test guidelines 412 and 413), STIS uses less animals and resources and offers additional information on organ burden and progression or regression of potential effects.

  8. Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

    SciTech Connect

    Kelsey, Chris R.; Horwitz, Mitchell E.; Chino, Junzo P.; Craciunescu, Oana; Steffey, Beverly; Folz, Rodney J.; Chao, Nelson J.; Rizzieri, David A.; Marks, Lawrence B.

    2011-11-01

    Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

  9. Toxicity of nanomaterials

    PubMed Central

    Sharifi, Shahriar; Behzadi, Shahed; Laurent, Sophie; Forrest, M. Laird; Stroeve, Pieter

    2015-01-01

    Nanoscience has matured significantly during the last decade as it has transitioned from bench top science to applied technology. Presently, nanomaterials are used in a wide variety of commercial products such as electronic components, sports equipment, sun creams and biomedical applications. There are few studies of the long-term consequences of nanoparticles on human health, but governmental agencies, including the United States National Institute for Occupational Safety and Health and Japan’s Ministry of Health, have recently raised the question of whether seemingly innocuous materials such as carbon-based nanotubes should be treated with the same caution afforded known carcinogens such as asbestos. Since nanomaterials are increasing a part of everyday consumer products, manufacturing processes, and medical products, it is imperative that both workers and end-users be protected from inhalation of potentially toxic NPs. It also suggests that NPs may need to be sequestered into products so that the NPs are not released into the atmosphere during the product’s life or during recycling. Further, non-inhalation routes of NP absorption, including dermal and medical injectables, must be studied in order to understand possible toxic effects. Fewer studies to date have addressed whether the body can eventually eliminate nanomaterials to prevent particle build-up in tissues or organs. This critical review discusses the biophysicochemical properties of various nanomaterials with emphasis on currently available toxicology data and methodologies for evaluating nanoparticle toxicity. PMID:22170510

  10. Late-onset respiratory distress after inhalation of laundry detergent.

    PubMed

    Wheeler, Derek S; Bonny, Andrea E; Ruddy, Richard M; Jacobs, Brian R

    2003-04-01

    Accidental poisoning with household cleaning products can pose significant risks to children. Exposure to granular laundry detergents accounts for a number of calls each year to poison control centers, though few of these exposures result in hospitalization. While caustic gastrointestinal injury resulting from ingestion of these highly alkaline cleaning agents is well-recognized, few reports address the potential damage to the respiratory tract that can occur following ingestion or inhalation of granular laundry detergent. We present a previously healthy 1-year-old who presented to the emergency department with Late-onset stridor and increased work of breathing following presumed inhalation of granular laundry detergent. Parents, primary care providers, and emergency department physicians need to be aware of the potential toxicity of these widely used household products.

  11. Intraosseous Versus Intravenous Infusion of Hydroxocobalamin for the Treatment Of Acute Severe Cyanide Toxicity in a Swine Model

    DTIC Science & Technology

    2014-11-01

    to smoke inhalation during fires involving many victims. Hydroxocobalamin has proven to be an effective antidote, but cannot be given intramuscularly...car-diac arrest in 50% of cyanide-exposed patients.1,2 In addition, smoke inhalation has produced toxic cyanide levels in over 30% of patients who...died after smoke inhalation .2–4 Hydroxocobalamin is approved by the U.S. Food and Drug Administration for the treatment of cyanide toxic- ity. We have

  12. Ninety-Day Subchronic Oral Toxicity Study of Pyridostigmine Bromide in Rats. Volume 1

    DTIC Science & Technology

    1990-05-01

    myasthenia gravis because of its relative lack of untoward effects in comparison with other anticholinesterases (2). This relative lack of clinical...treatment of myasthenia gravis . Objecrive of Study The objective of this study was to determine the 90-day subchronic toxicity of pyridostigmine bromide in

  13. SUBCHRONIC TOXICITY OF 1,3,5-TRINITROBENZENE IN FISCHER 344 RATS

    EPA Science Inventory

    The subchronic toxicity of 1,3,5-trinitrobenzene (TNB) in male and female Fischer 344 rats was evaluated by feeding a powdered certified laboratory diet containing 0, 66.7, 400 and 800 mg TNB/kg diet for 90 days. The calculated average TNB intake was 4.29, 24.70, and 49.28 mg/kg...

  14. INHALATION EXPOSURE-RESPONSE METHODOLOGY

    EPA Science Inventory

    The Inhalation Exposure-Response Analysis Methodology Document is expected to provide guidance on the development of the basic toxicological foundations for deriving reference values for human health effects, focusing on the hazard identification and dose-response aspects of the ...

  15. Parental Influence on Inhalant Use

    ERIC Educational Resources Information Center

    Baltazar, Alina; Hopkins, Gary; McBride, Duane; Vanderwaal, Curt; Pepper, Sara; Mackey, Sarah

    2013-01-01

    The purpose of this article is to examine the dynamics of the relationship between parents and their adolescent children and their association with lifetime and past-month inhalant usage. The population studied was seventh- through ninth-grade students in rural Idaho (N = 570). The authors found a small, but consistent, significant inverse…

  16. TARGETED DELIVERY OF INHALED PROTEINS

    EPA Science Inventory

    ETD-02-047 (Martonen) GPRA # 10108

    TARGETED DELIVERY OF INHALED PROTEINS
    T. B. Martonen1, J. Schroeter2, Z. Zhang3, D. Hwang4, and J. S. Fleming5
    1Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park...

  17. Inhalant Use in Florida Youth

    ERIC Educational Resources Information Center

    Siqueira, Lorena; Crandall, Lee A.

    2006-01-01

    Purpose: To determine (1) the prevalence of use, (2) risk and protective factors for use of inhalants in Florida youth. Methods: The Florida Youth Substance Abuse Survey 2004 is a comprehensive assessment of youth substance abuse attitudes and practices obtained by sampling youth from sixty-five counties. Results: The sample consisted of 60,345…

  18. INHALATION TOXICOLOGY METHODS: The Generation and Characterization of Exposure Atmospheres and Inhalational Exposures

    PubMed Central

    Chen, Lung-Chi; Lippmann, Morton

    2015-01-01

    In this review, we outline the need for laboratory-based inhalation toxicology studies, the historical background on adverse health effects of airborne toxicants, and the benefits of advance planning for the building of analytic options into the study design to maximize the scientific gains to be derived from the investments in the study. We then discuss methods for: 1) the generation and characterization of exposure atmospheres for inhalation exposures in humans and laboratory animals; 2) their delivery and distribution into and within whole-body exposure chambers, head-only exposure chambers, face-masks, and mouthpieces or nasal catheters; 3) options for on-line functional assays during and between exposures; and 4) options for serial non-invasive assays of response. In doing so, we go beyond exposures to single agents and simple mixtures, and include methods for evaluating biological responses to complex environmental mixtures. We also emphasize that great care should be taken in the design and execution of such studies so that the scientific returns can be maximized both initially, and in follow-up utilization of archived samples of the exposure atmospheres, excreta, and tissues collected for histology. PMID:25645246

  19. Synthetic vitreous fibers--inhalation studies.

    PubMed

    McConnell, E E

    1994-12-01

    Synthetic vitreous fibers (SVFs), often referred to as "man-made vitreous fibers," are a class of materials that have their major uses for insulation against heat and sound. The original fibers are produced by melting various types of rock, clay, etc. and then blowing or extruding them into fibers of particular properties. During production and use small fractions of airborne fibers can be generated. Because of this a series of state-of-the-art inhalation studies was initiated to study the possible health hazards presented by the four major types of vitreous materials [two types of insulation glass wool, rock wool, slag wool, and four types of refractory ceramic fibers (RCF)] found in the workplace or to which the general public may be exposed. Rats and hamsters (30 mg/m3 kaolin-based RCF only) were exposed by nose-only inhalation to 3, 16, or 30 mg/m3 for 6 hr/day, 5 days/week, for 18 (hamsters) or 24 (rats) months and were held for lifetime observation (until approximately 20% survival) to study the chronic toxicity and potential carcinogenic activity of these classes of SVFs. Chrysotile or crocidolite asbestos served as positive controls. All of the fibers stimulated an inflammatory response characterized by an increase in the number of pulmonary macrophages at the level of the terminal bronchioles and proximal alveoli. RCF produced interstitial fibrosis in the walls of the proximal alveoli as early as 3 months and rock wool by 12 months. The only fiber which showed carcinogenic activity was RCF which produced a dose-related increase in both primary lung neoplasms (rats only) and mesotheliomas (rats and hamsters).

  20. Systems Pharmacology Approach Toward the Design of Inhaled Formulations of Rifampicin and Isoniazid for Treatment of Tuberculosis

    PubMed Central

    Cilfone, NA; Pienaar, E; Thurber, GM; Kirschner, DE; Linderman, JJ

    2015-01-01

    Conventional oral therapies for the treatment of tuberculosis are limited by poor antibiotic distribution in granulomas, which contributes to lengthy treatment regimens and inadequate bacterial sterilization. Inhaled formulations are a promising strategy to increase antibiotic efficacy and reduce dose frequency. We develop a multiscale computational approach that accounts for simultaneous dynamics of a lung granuloma, carrier release kinetics, pharmacokinetics, and pharmacodynamics. Using this computational platform, we predict that a rationally designed inhaled formulation of isoniazid given at a significantly reduced dose frequency has better sterilizing capabilities and reduced toxicity than the current oral regimen. Furthermore, we predict that inhaled formulations of rifampicin require unrealistic carrier antibiotic loadings that lead to early toxicity concerns. Lastly, we predict that targeting carriers to macrophages has limited effects on treatment efficacy. Our platform can be extended to account for additional antibiotics and provides a new tool for rapidly prototyping the efficacy of inhaled formulations. PMID:26225241

  1. Toxic leucoencephalopathy after 'chasing the dragon'.

    PubMed

    Singh, Rajinder; Saini, Monica

    2015-06-01

    Toxic leucoencephalopathy (TLE) is a rare neurological complication of heroin abuse. 'Chasing the dragon' is an inhalational mode of heroin abuse that originated in Southeast Asia. Intriguingly, no cases of TLE have been reported from this region, although the inhalational mode of heroin abuse is common. We herein report the case of a middle-aged man with a history of polysubstance abuse who presented with progressive neurological symptoms and progressed to an uncommunicative state. While the initial impression was that of iatrogenic parkinsonism, diffuse leucoencephalopathy with sparing of the cerebellum was noted on magnetic resonance imaging. In view of his history of inhalational heroin abuse close to the onset of the neurological symptoms, a diagnosis of TLE was made. No clinical improvement was noted with administration of a dopaminergic agent. This is the first known case of delayed TLE following heroin inhalation from Southeast Asia with the unusual feature of cerebellar sparing.

  2. Toxic megacolon

    MedlinePlus

    ... disease - toxic megacolon; Crohn disease - toxic megacolon; Ulcerative colitis - toxic megacolon ... people with an inflamed colon due to: Ulcerative colitis , or Crohn disease that is not well controlled ...

  3. Toxicological Assessments of Rats Exposed Prenatally to Inhaled Vapors of Gasoline and Gasoline-Ethanol Blends

    EPA Science Inventory

    The primary alternative to petroleum-based fuels is ethanol, which is blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ...

  4. [Effects of Instruction on Inhalation Techniques Using iPads - Web Application "Inhalation Lessons"].

    PubMed

    Kogawa, Noriko; Ito, Reiko; Gon, Yasuhiro; Maruoka, Shuichiro; Hashimoto, Shu

    2015-12-01

    Instruction on inhalation techniques for chronic obstructive pulmonary disease(COPD)and asthma patients being treated with inhalants have sufficient therapeutic effects and are important to maintain adherence. However, problems continue to exist, including time constraints of medical staff that have a large number of patients and a lack of knowledge on inhalation instruction methods. A web application,"Inhalation Lessons,'for the iPad has been developed. It explains inhalation methods, and consists of videos and review tests. Instruction on inhalation techniques was performed using this application for patients that use Diskus, and the effects were examined. As a result, there are significant improvements in the inhalation techniques of patients after viewing the"Inhalation Lessons'application. Uniform instruction on inhalation techniques can be performed even in the field of homecare.

  5. [Inhalant abusers and psychiatric symptoms].

    PubMed

    Okudaira, K; Yabana, T; Takahashi, H; Iizuka, H; Nakajima, K; Saito, A

    1996-01-01

    There are different opinions about the cause of chronic psychiatric symptoms observed in drug abusers between Japanese and foreign psychiatrists. The Japanese seem to recognize the chronic psychosis as the result of drug abuse. In the other hand, foreigners diagnose these cases as dual diagnosis of drug abuse and psychosis. Authors studied the problem in this research. One of the authors has examined 120 inhalant abusers of all, in- and out-patients in Kanagawa Prefectural Center of Psychiatry, Serigaya Hospital from 1991 to 1995. These patients were classified into three groups: psychosis group (23 patients), dependence group (51 patients) and abuse group (46 patients) according to their clinical courses and psychiatric symptoms. The psychosis group consists of patients who showed psychiatric symptoms such as hallucination, delusion and thought disturbance for long time after detoxification. The dependence group contains patients whose inhalant dependence was severe and met DSM-4 Diagnostic Criteria for Substance Dependence, but manifested no chronic psychiatric symptoms after detoxification. The patients belonging to abuse group were at the earlier stages of inhalant abuse and had no chronic psychiatric symptoms. The average age of the first inhalant abuse was 14.7 years old in the psychosis group, 14.8 years in the dependence group and 14.7 years in the abuse group. The average years of abuse was 9.0 years in the psychosis group, and 8.5 years in the dependence group. There was little difference between these two groups. The psychosis patients manifested chronic symptoms 5.7 years on average after the first abuse of inhalants. About one forth (26.1%) of the psychosis patients and only 5.9% of the dependence patients had family history of schizophrenia. The difference was statistically significant. These results suggest that chronic psychiatric symptoms are caused not only by inhalant abuse, but also by the genetic factors of psychosis of each patient. There have

  6. Toxic Synovitis

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Toxic Synovitis KidsHealth > For Parents > Toxic Synovitis A A A ... and causes no long-term problems. About Toxic Synovitis Toxic synovitis (also known as transient synovitis ) is ...

  7. Suicidal carbon monoxide inhalation of exhaust fumes. Investigation of cases

    SciTech Connect

    Tsunenari, S.; Yonemitsu, K.; Kanda, M.; Yoshida, S.

    1985-09-01

    The inhalation of automobile exhaust gases is a relatively frequent suicidal method. Two such cases of special interest to forensic pathology and toxicology have been introduced. In case 1, a suicide note disclosed the victim's mental state, the inside conditions of the car, and toxic effects of automobile exhaust. In case 2, a reconstruction experiment has revealed important factors for the investigation of the scene, such as the size of a vinyl hose, the conditions of connecting site of the hose with the exhaust pipe, etc.

  8. Inhalation therapy in mechanical ventilation

    PubMed Central

    Maccari, Juçara Gasparetto; Teixeira, Cassiano; Gazzana, Marcelo Basso; Savi, Augusto; Dexheimer-Neto, Felippe Leopoldo; Knorst, Marli Maria

    2015-01-01

    Patients with obstructive lung disease often require ventilatory support via invasive or noninvasive mechanical ventilation, depending on the severity of the exacerbation. The use of inhaled bronchodilators can significantly reduce airway resistance, contributing to the improvement of respiratory mechanics and patient-ventilator synchrony. Although various studies have been published on this topic, little is known about the effectiveness of the bronchodilators routinely prescribed for patients on mechanical ventilation or about the deposition of those drugs throughout the lungs. The inhaled bronchodilators most commonly used in ICUs are beta adrenergic agonists and anticholinergics. Various factors might influence the effect of bronchodilators, including ventilation mode, position of the spacer in the circuit, tube size, formulation, drug dose, severity of the disease, and patient-ventilator synchrony. Knowledge of the pharmacological properties of bronchodilators and the appropriate techniques for their administration is fundamental to optimizing the treatment of these patients. PMID:26578139

  9. Neptunium-237 inhalation in rats.

    PubMed

    Sullivan, M F; Ruemmler, P S; Buschbom, R L

    1986-12-01

    Groups of rats were exposed to aerosols of 237Np nitrate to determine clearance rates, retention and distribution at various intervals after inhalation. Initial lung burdens (ILB) after 237Np inhalation by three treatment groups were 0.12, 0.19 and 0.37 mu Ci/kg, respectively. Radiochemical analyses of animals killed at 4, 8, 14, 28 and 90 d, as well as data for others maintained until they became moribund, showed that their lung clearance followed a three-compartment model, clearance half-times for which were 1, 35, and 10,000 d, respectively. Only 3% of the ILB was retained after 90 d; 12% of that burden had translocated to the skeleton at 750 d; the half-time for skeletal retention was 2500 d. A single tumor was the only malignancy detected in the lungs of the 35 animals allowed to survive the early phase of the study.

  10. Inhaled anesthetics: an historical overview.

    PubMed

    Whalen, Francis X; Bacon, Douglas R; Smith, Hugh M

    2005-09-01

    Inhalational agents have played a pivotal role in anesthesia history. The first publicly demonstrated anesthetic of the modern era, diethyl ether, was an inhalational anesthetic. The attributes of a good agent, ability to rapidly induce anesthesia, with limited side effects has led research efforts for over a hundred and fifty years. The explosion hazard was largely conquered with the development of the halogenated agents in the 1950s. Rapid emergence, with limited nausea and vomiting continue to drive discovery efforts, yet the 'modern' agents continue to improve upon those in the past. The future holds promise, but perhaps the most interesting contrast over time is the ability to rapidly introduce new agents into practice. From James Young Simpson's dinner table one evening to the operating suite the next day, modern agents take decades from first synthesis to clinical introduction.

  11. Inhalation of Talc Induces Infiltration of Macrophages and Upregulation of Manganese Superoxide Dismutase in Rats.

    PubMed

    Shim, Ilseob; Kim, Hyun-Mi; Yang, Sangyoung; Choi, Min; Seo, Gyun-Baek; Lee, Byung-Woo; Yoon, Byung-Il; Kim, Pilje; Choi, Kyunghee

    2015-01-01

    Talc is a mineral that is widely used in cosmetic products, antiseptics, paints, and rubber manufacturing. Although the toxicological effects of talc have been studied extensively, until now no detailed inhalation study of talc focusing on oxidative stress has been done. This repeated 4 weeks whole-body inhalation toxicity study of talc involved Sprague-Dawley rats. Male and female groups of rats were exposed to inhaled talc at 0, 5, 50, and 100 mg/m(3) for 6 hours daily, 5 days/week for 4 weeks. The objective was to identify the 4-week inhalation toxicity of talc and investigate antioxidant activity after exposure to talc. There were no treatment-related symptoms or mortality in rats treated with talc. Glucose (GLU) was decreased significantly in male rats exposed to 50 and 100 mg/m(3) of talc. Histopathological examination revealed infiltration of macrophages on the alveolar walls and spaces near the terminal and respiratory bronchioles. In male and female rats exposed to 100 mg/m(3) talc, expression of superoxide dismutase 2, a typical biological indicator of oxidative damage, was significantly increased. Thus, inhalation of talc induces macrophage aggregations and oxidative damage in the lung.

  12. Thinner inhalation effects on oxidative stress and DNA repair in a rat model of abuse.

    PubMed

    Martínez-Alfaro, Minerva; Cárabez-Trejo, Alfonso; Gallegos-Corona, Marco-Antonio; Pedraza-Aboytes, Gustavo; Hernández-Chan, Nancy Georgina; Leo-Amador, Guillermo Enrique

    2010-04-01

    Humans can come into contact with thinner by occupational exposure or by intentional inhalation abuse. Numerous studies of workers for genotoxic effects of thinner exposure have yielded conflicting results, perhaps because co-exposure to variable other compounds cannot be avoided in workplace exposure studies. In contrast, there is no data concerning the genotoxic effects of intentional inhalation abuse. The aim of this project was to examine the genotoxic effects of thinner inhalation in an animal model of thinner abuse (rats exposed to 3000 ppm toluene, a high solvent concentration over a very short, 15 min time period, twice a day for 6 weeks). The data presented here provides evidence that thinner inhalation in our experimental conditions is able to induce weight loss, lung abnormalities and oxidative stress. This oxidative stress induces oxidative DNA damage that is not a characteristic feature of genotoxic damage. No significant difference in DNA damage and DNA repair (biomarkers of genotoxicity) in lymphocytes from thinner-treated and control rats was found. Lead treatment was used as a positive control in these assays. Finally, bone marrow was evaluated as a biomarker of cellular alteration associated with thinner inhalation. The observed absence of hemopoietic and genetic toxicity could be explained in part by the absence of benzene, the only carcinogenic component of thinner; however, benzene is no longer a common component of thinner. In conclusion, thinner did not cause genotoxic effects in an experimental model of intentional abuse despite the fact that thinner inhalation induces oxidative stress.

  13. Inhaled Therapies for Pulmonary Hypertension.

    PubMed

    Hill, Nicholas S; Preston, Ioana R; Roberts, Kari E

    2015-06-01

    The inhaled route has a number of attractive features for treatment of pulmonary hypertension, including delivery of drug directly to the target organ, thus enhancing pulmonary specificity and reducing systemic adverse effects. It can also improve ventilation/perfusion matching by dilating vessels supplying ventilated regions, thus improving gas exchange. Furthermore, it can achieve higher local drug concentrations at a lower overall dose, potentially reducing drug cost. Accordingly, a number of inhaled agents have been developed to treat pulmonary hypertension. Most in current use are prostacyclins, including epoprostenol, which has been cleared for intravenous applications but is used off-label in acute care settings as a continuously nebulized medication. Aerosolized iloprost and treprostinil are both prostacyclins that have been cleared by the FDA to treat pulmonary arterial hypertension (PAH). Both require frequent administration (6 and 4 times daily, respectively), and both have a tendency to cause airway symptoms, including cough and wheeze, which can lead to intolerance. These agents cannot be used to substitute for the infused routes of prostacyclin because they do not permit delivery of medication at high doses. Inhaled nitric oxide (INO) is cleared for the treatment of primary pulmonary hypertension in newborns. It is also used off-label to test acute vasoreactivity in PAH during right-heart catheterization and to treat acute right-heart failure in hospitalized patients. In addition, some studies on long-term application of INO either have been recently completed with results pending or are under consideration. In the future, because of its inherent advantages in targeting the lung, the inhaled route is likely to be tested using a variety of small molecules that show promise as PAH therapies.

  14. Brain permeability of inhaled corticosteroids.

    PubMed

    Arya, Vikram; Issar, Manish; Wang, Yaning; Talton, James D; Hochhaus, Guenther

    2005-09-01

    The aim of this study was to evaluate if the permeability of inhaled corticosteroids entering the brain is reduced and if P-glycoprotein (P-gp) transporters are involved. Currently employed inhaled corticosteroids were given intravenously and intratracheally to rats at a dose of 100 microg kg-1. An ex-vivo receptor binding assay was used to monitor over 12 h the glucocorticoid receptor occupancy in the brain and a systemic reference organ (kidney). The involvement of P-gp in the brain permeability of triamcinolone acetonide was assessed in wild-type mice and mdr1a(-/-) knockout mice (mice lacking the gene for expressing P-gp). After both forms of administration, the average brain receptor occupancies were 20-56% of those of the reference organ, with the more lipophilic drugs showing a more pronounced receptor occupation. While the receptor occupancies in the liver of wild-type and mdr1a(-/-) mice were similar after administration of triamcinolone acetonide, brain receptor occupancies in mdr1a(-/-) mice were significantly greater (mdr1a(-/-): 47.6%, 40.2-55.0%, n=14; 2; wild-type: 11.5+/-33.0%, n=14; 3). Penetration into the brain for inhaled corticosteroids (especially those of lower lipophilicity) is reduced. Experiments in mdr1a(-/-) mice confirmed the involvement of P-gp transporters. Further studies are needed to assess whether potential drug interactions at the transporter level are of pharmacological significance.

  15. Another Alternative: A 90-Day Contractual Detoxification Treatment Program

    ERIC Educational Resources Information Center

    Kahn, Robert B.; And Others

    1978-01-01

    In May 1974, Fresno County's Narcotic Abuse Treatment Program began a 21-day outpatient methadone detoxification treatment modality. The purpose of this paper is to examine this alternative treatment modality, its characteristics, its therapeutic outcomes and the rationale for its use. (Author)

  16. Acute Inhalation Toxicity of Pyrotechnically Disseminated Terephthalic Acid

    DTIC Science & Technology

    1988-07-01

    calcium concentrations in the bladder, followed by urolithiasis with irritation induced hyperplasia and neoplasms. However, these effects only occur...R.W., Popp, J.A., Heck, H., "Chemical Urolithiasis , 1. Characteristics of Bladder Stone Induction by Terephthalic Acid and Dimethyl Terephthalate in

  17. Inhalation Toxicity of Single Materials and Mixtures. Phase 2.

    DTIC Science & Technology

    1991-03-29

    Lymphocytes (percent leukocytes counted) MONO . monocytes (percent leukocytes counted) EOS - eosinophiLs (percent leukocytes counted) BASO - basophiLs...leukocytes counted) LYMPH - lymphocytes (percent leukocytes counted) MONO - monocytes (percent leukocytes counted) EOS - eosinophils (percent leukocytes...Ex 24 24 0 9 12 12 PULMONARY LN # Ex 21 22 0 8 10 6 Hyperptasia 0 2 0.18 0 8 2.38 0 0 Granu loma 0 0 0 0 6 1.70 6 3.83 Pigment 0 0 0 8 3.00 0 0

  18. Chronic Inhalation Toxicity of Unsymmetrical Dimethylhydrazine: Oncogenic Effects

    DTIC Science & Technology

    1984-10-01

    frequent findings in all groups of exposed and control rats and were part of the complex of chronic murine pneumonia commonly seen in rats. Alveolar...2-methylhydrazino)-p-tolumide HCI (procarbazine hydro- chloride), its degradation products, other hydrazines, and isonico- tinic acid hydrazide , J

  19. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... (1) Each animal must be assigned a unique identification number. A system to assign animals to test... minimum of four measurements should be taken. (4) During the development of the generating system..., evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic...

  20. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... (1) Each animal must be assigned a unique identification number. A system to assign animals to test... minimum of four measurements should be taken. (4) During the development of the generating system..., evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic...

  1. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... (1) Each animal must be assigned a unique identification number. A system to assign animals to test... minimum of four measurements should be taken. (4) During the development of the generating system..., evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic...

  2. Oscillometry complements spirometry in evaluation of subjects following toxic inhalation

    PubMed Central

    Berger, Kenneth I.; Turetz, Meredith; Liu, Mengling; Shao, Yongzhao; Kazeros, Angeliki; Parsia, Sam; Caplan-Shaw, Caralee; Friedman, Stephen M.; Maslow, Carey B.; Marmor, Michael; Goldring, Roberta M.

    2015-01-01

    The World Trade Center (WTC) destruction released dust and fumes into the environment. Although many community members developed respiratory symptoms, screening spirometry was usually normal. We hypothesised that forced oscillation testing would identify functional abnormalities undetected by spirometry and that symptom severity would relate to magnitude of abnormalities measured by oscillometry. A symptomatic cohort (n=848) from the Bellevue Hospital WTC Environmental Health Center was evaluated and compared to an asymptomatic cohort (n=475) from the New York City Department of Health WTC Health Registry. Spirometry and oscillometry were performed. Oscillometry measurements included resistance (R5) and frequency dependence of resistance (R5−20). Spirometry was normal for the majority of subjects (73.2% symptomatic versus 87.6% asymptomatic, p<0.0001). In subjects with normal spirometry, R5 and R5−20 were higher in symptomatic versus asymptomatic subjects (median (interquartile range) R5 0.436 (0.206) versus 0.314 (0.129) kPa·L−1·s−1, p<0.001; R5−20 0.075 (0.085) versus 0.004 (0.042) kPa·L−1·s−1, p<0.0001). In symptomatic subjects, R5 and R5−20 increased with increasing severity and frequency of wheeze (p<0.05). Measurement of R5–20 correlated with the presence and severity of symptoms even when spirometry was within normal limits. These findings are in accord with small airway abnormalities as a potential explanation of the respiratory symptoms. PMID:27730155

  3. Oscillometry complements spirometry in evaluation of subjects following toxic inhalation.

    PubMed

    Berger, Kenneth I; Turetz, Meredith; Liu, Mengling; Shao, Yongzhao; Kazeros, Angeliki; Parsia, Sam; Caplan-Shaw, Caralee; Friedman, Stephen M; Maslow, Carey B; Marmor, Michael; Goldring, Roberta M; Reibman, Joan

    2015-10-01

    The World Trade Center (WTC) destruction released dust and fumes into the environment. Although many community members developed respiratory symptoms, screening spirometry was usually normal. We hypothesised that forced oscillation testing would identify functional abnormalities undetected by spirometry and that symptom severity would relate to magnitude of abnormalities measured by oscillometry. A symptomatic cohort (n=848) from the Bellevue Hospital WTC Environmental Health Center was evaluated and compared to an asymptomatic cohort (n=475) from the New York City Department of Health WTC Health Registry. Spirometry and oscillometry were performed. Oscillometry measurements included resistance (R5) and frequency dependence of resistance (R5-20). Spirometry was normal for the majority of subjects (73.2% symptomatic versus 87.6% asymptomatic, p<0.0001). In subjects with normal spirometry, R5 and R5-20 were higher in symptomatic versus asymptomatic subjects (median (interquartile range) R5 0.436 (0.206) versus 0.314 (0.129) kPa·L(-1)·s(-1), p<0.001; R5-20 0.075 (0.085) versus 0.004 (0.042) kPa·L(-1)·s(-1), p<0.0001). In symptomatic subjects, R5 and R5-20 increased with increasing severity and frequency of wheeze (p<0.05). Measurement of R5-20 correlated with the presence and severity of symptoms even when spirometry was within normal limits. These findings are in accord with small airway abnormalities as a potential explanation of the respiratory symptoms.

  4. 40 CFR 721.4472 - Phenyl, alkyl, hydroxyalkyl substituted imidazole (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant... test guideline) followed by a (90-day subchronic inhalation study in rats (40 CFR 799.9346). A...

  5. 40 CFR 721.4472 - Phenyl, alkyl, hydroxyalkyl substituted imidazole (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant... test guideline) followed by a (90-day subchronic inhalation study in rats (40 CFR 799.9346). A...

  6. 40 CFR 721.4472 - Phenyl, alkyl, hydroxyalkyl substituted imidazole (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant... test guideline) followed by a (90-day subchronic inhalation study in rats (40 CFR 799.9346). A...

  7. 40 CFR 721.4472 - Phenyl, alkyl, hydroxyalkyl substituted imidazole (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant... test guideline) followed by a (90-day subchronic inhalation study in rats (40 CFR 799.9346). A...

  8. 40 CFR 721.4472 - Phenyl, alkyl, hydroxyalkyl substituted imidazole (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant... test guideline) followed by a (90-day subchronic inhalation study in rats (40 CFR 799.9346). A...

  9. [Inhalation therapy: inhaled generics, inhaled antidotes, the future of anti-infectives and the indications of inhaled pentamidine. GAT aerosolstorming, Paris 2012].

    PubMed

    Peron, N; Le Guen, P; Andrieu, V; Bardot, S; Ravilly, S; Oudyi, M; Dubus, J-C

    2013-12-01

    The working group on aerosol therapy (GAT) of the Société de pneumologie de langue française (SPLF) organized its third "Aerosolstorming" in 2012. During the course of one day, different aspects of inhaled therapy were discussed, and these will be treated separately in two articles, this one being the first. Inhaled products represent a large volume of prescriptions both in the community and in hospital settings and they involve various specialties particularly ENT and respiratory care. Technical aspects of the development of these products, their mode of administration and compliance with their indications are key elements for the effective therapeutic use of inhaled treatments. In this first article, we will review issues concerning generic inhaled products, the existence of inhaled antidotes, new anti-infective agents and indications for inhaled pentamidine.

  10. Incinerator air emissions: Inhalation exposure perspectives

    SciTech Connect

    Rogers, H.W.

    1995-12-01

    Incineration is often proposed as the treatment of choice for processing diverse wastes, particularly hazardous wastes. Where such treatment is proposed, people are often fearful that it will adversely affect their health. Unfortunately, information presented to the public about incinerators often does not include any criteria or benchmarks for evaluating such facilities. This article describes a review of air emission data from regulatory trial burns in a large prototype incinerator, operated at design capacity by the US Army to destroy chemical warfare materials. It uses several sets of criteria to gauge the threat that these emissions pose to public health. Incinerator air emission levels are evaluated with respect to various toxicity screening levels and ambient air levels of the same pollutants. Also, emission levels of chlorinated dioxins and furans are compared with emission levels of two common combustion sources. Such comparisons can add to a community`s understanding of health risks associated with an incinerator. This article focuses only on the air exposure/inhalation pathway as related to human health. It does not address other potential human exposure pathways or the possible effects of emissions on the local ecology, both of which should also be examined during a complete analysis of any major new facility.

  11. [Advances in the research of pathogenesis and treatment of severe smoke inhalation injury].

    PubMed

    Feng, Shengjuan; Jia, Chiyu; Liu, Zhen; Lyu, Xiaowu

    2016-02-01

    Among the fire victims, respiratory tract injury resulted from smoke inhalation is the major cause of death. Particulate substances in smoke, toxic and harmful gas, and chemical substances act together would rapidly induce the occurrence of dramatic pathophysiologic reaction in the respiratory tract, resulting in acute injury to the respiratory tract, thus inducing serious injury to it and acute respiratory distress syndrome, leading to death of the victims. In recent years, the pathophysiologic mechanism of severe smoke inhalation injury has been gradually clarified, thus appreciable advances in its treatment have been achieved. This paper is a brief review of above-mentioned aspects.

  12. Computer controlled multi-walled carbon nanotube inhalation exposure system.

    PubMed

    McKinney, Walter; Chen, Bean; Frazer, Dave

    2009-10-01

    Inhalation exposure systems are necessary tools for determining the dose-response relationship of inhaled toxicants under a variety of exposure conditions. The objective of this project was to develop an automated computer controlled system to expose small laboratory animals to precise concentrations of airborne multi-walled carbon nanotubes (MWCNT). An aerosol generator was developed which was capable of suspending a respirable fraction of multi-walled carbon nanotubes from bulk material. The output of the generator was used to expose small laboratory animals to constant aerosol concentrations up to 12 mg/m(3). Particle distribution and morphology of the MWCNT aerosol delivered to the exposure chamber were measured and compared to samples previously taken from air inside a facility that produces MWCNT. The comparison showed the MWCNT generator was producing particles similar in size and shape to those found in a work environment. The inhalation exposure system combined air flow controllers, particle monitors, data acquisition devices, and custom software with automatic feedback control to achieve constant and repeatable exposure chamber temperature, relative humidity, pressure, aerosol concentration, and particle size distribution. The automatic control algorithm was capable of maintaining the mean aerosol concentration to within 0.1 mg/m(3) of the selected target value, and it could reach 95% of the target value in less than 10 minutes during the start-up of an inhalation exposure. One of the major advantages of this system was that once the exposure parameters were selected, a minimum amount of operator intervention was required over the exposure period.

  13. 75 FR 28610 - Draft EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-21

    ... AGENCY Draft EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of Public Comment Period. SUMMARY: EPA is announcing a 90-day public comment period for the external review draft entitled, ``EPA's Reanalysis of...

  14. EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments (External Review Draft)

    EPA Science Inventory

  1. Principles and Procedures for Evaluating the Toxicity of Household Substances. Revised.

    ERIC Educational Resources Information Center

    National Academy of Sciences - National Research Council, Washington, DC. Assembly of Life Sciences.

    This report was prepared for use by the professional toxicologist. It contains chapters on ingestion exposure, dermal and dye toxicity tests, inhalation exposure, chronic toxicity and carcinogenicity tests, mutagenicity tests, reproduction and teratogenicity tests, and behavioral toxicity tests. In addition, regulations under the Federal Hazardous…

  2. Inhalant initiation and the relationship of inhalant use to the use of other substances.

    PubMed

    Shamblen, Stephen R; Miller, Ted

    2012-01-01

    Conventional wisdom suggests that inhalant use is primarily isolated to youthful experimentation; however, a growing body of evidence suggests that inhalant use (a) occurs after use of common substances of experimentation (e.g., alcohol, marijuana), (b) can persist into later life, and (c) is associated with severe consequences. The current study examined the sequencing of substances relative to inhalants and the post-initiation correlates of inhalant use between youth and young adulthood in nationally representative Add Health data. Analyses examined the relationship of substance of initiation to use of other substances, as well as an examination of the relationship between substance use and consequences. The analyses suggest that (a) those initiating their substance use careers with inhalants often go on to use hard drugs, (b) inhalant use likely occurs after alcohol and marijuana use, and (c) inhalant use during adolescence was associated with health and criminal consequences in both adolescence and young adulthood.

  3. How to use an inhaler - with spacer

    MedlinePlus

    ... After using your inhaler, rinse your mouth with water, gargle, and spit. This helps reduce side effects from your medicine. ... If you see powder in or around the hole, clean your inhaler. ... cap in warm water. Let them air dry overnight. In the morning, ...

  4. How to use an inhaler - no spacer

    MedlinePlus

    ... After using your inhaler, rinse your mouth with water, gargle, and spit. This helps reduce side effects from your medicine. ... If you see powder in or around the hole, clean your inhaler. ... cap in warm water. Let them air dry overnight. In the morning, ...

  5. Investigation of Inhalation Anthrax Case, United States

    PubMed Central

    Blaney, David; Shadomy, Sean; Lehman, Mark; Pesik, Nicki; Tostenson, Samantha; Delaney, Lisa; Tiller, Rebekah; DeVries, Aaron; Gomez, Thomas; Sullivan, Maureen; Blackmore, Carina; Stanek, Danielle; Lynfield, Ruth

    2014-01-01

    Inhalation anthrax occurred in a man who vacationed in 4 US states where anthrax is enzootic. Despite an extensive multi-agency investigation, the specific source was not detected, and no additional related human or animal cases were found. Although rare, inhalation anthrax can occur naturally in the United States. PMID:24447835

  6. Investigation of inhalation anthrax case, United States.

    PubMed

    Griffith, Jayne; Blaney, David; Shadomy, Sean; Lehman, Mark; Pesik, Nicki; Tostenson, Samantha; Delaney, Lisa; Tiller, Rebekah; DeVries, Aaron; Gomez, Thomas; Sullivan, Maureen; Blackmore, Carina; Stanek, Danielle; Lynfield, Ruth

    2014-02-01

    Inhalation anthrax occurred in a man who vacationed in 4 US states where anthrax is enzootic. Despite an extensive multi-agency investigation, the specific source was not detected, and no additional related human or animal cases were found. Although rare, inhalation anthrax can occur naturally in the United States.

  7. Parent's Guide to Preventing Inhalant Abuse

    MedlinePlus

    ... child or someone you know is an inhalant abuser, what can you do to help? Be alert for symptoms of inhalant abuse. If you suspect there's a problem, you should consider seeking professional help. Contact a local drug rehabilitation center or other services available in your ...

  8. Experimental inhalation injury in the goat.

    PubMed

    Walker, H L; McLeod, C G; McManus, W F

    1981-11-01

    Inhalation injuries are usually produced by inhalation of gaseous or particulate products of incomplete combustion and are rarely due to heat per se unless steam is inhaled. The clinical and anatomic characteristics of an appropriate animal model should mimic the disease encountered clinically. A model of inhalation injury has been produced in anesthetized goats through the use of a modified bee smoker. The smoke is delivered at a low temperature and contains byproducts of incomplete combustion. This reproducible injury produces necrotic tracheobronchitis and bronchiolitis with pseudomembrane and cast formation in association with mild multifocal atelectasis and bronchopneumonia. These lesions spontaneously resolve within 3 weeks without supportive therapy. The upper trachea, protected from smoke injury by the inflated cuff of the endotracheal tube, showed no evidence of injury. This nonlethal injury is proposed as an appropriate model for evaluation of the pathophysiology and treatment of inhalation injury.

  9. Inhalants

    MedlinePlus

    ... area of the brain that gets damaged. The hippocampus, for example, is responsible for memory, so someone ... stimulants like cocaine and narcotics like heroin or morphine can kill you immediately. The old standbys like ...

  10. Inhalants

    MedlinePlus

    ... Naloxone Pain Prevention Treatment Trends & Statistics Women and Drugs Publications Funding Funding Opportunities Clinical Research Post-Award Concerns General Information Grant & Contract Application ...

  11. Comparative pathology of the nasal mucosa in laboratory animals exposed to inhaled irritants.

    PubMed Central

    Harkema, J R

    1990-01-01

    The nasal cavity is susceptible to chemically induced injury as a result of exposure to inhaled irritants. Some responses of the nasal mucosa to inhaled toxicants are species specific. These species-related differences in response may be due to variations in structural, physiologic, and biochemical factors, such as gross nasal cavity structure, distribution of luminal epithelial cell populations along the nasal airway, intranasal airflow patterns, nasal mucociliary apparatus, and nasal xenobiotic metabolism among animal species. This paper reviews the comparative anatomy and irritant-induced pathology of the nasal cavity in laboratory animals. The toxicologist, pathologist, and environmental risk assessor must have a good working knowledge of the similarities and differences in normal nasal structure and response to injury among species before they can select animal models for nasal toxicity studies, recognize toxicant-induced lesions in the nasal airway, and extrapolate experimental results to estimate the possible effects of an inhaled toxicant on the human nasal airway. Images PLATE 1. PLATE 2. A PLATE 2. B PLATE 3. PMID:2116960

  12. Inhalation and Dietary Exposure to PCBs in Urban and Rural Cohorts via Congener-Specific Measurements

    PubMed Central

    2015-01-01

    Polychlorinated biphenyls (PCBs) are a group of 209 persistent organic pollutants, whose documented carcinogenic, neurological, and respiratory toxicities are expansive and growing. However, PCB inhalation exposure assessments have been lacking for North American ambient conditions and lower-chlorinated congeners. We assessed congener-specific inhalation and dietary exposure for 78 adolescent children and their mothers (n = 68) in the Airborne Exposure to Semi-volatile Organic Pollutants (AESOP) Study. Congener-specific PCB inhalation exposure was modeled using 293 measurements of indoor and outdoor airborne PCB concentrations at homes and schools, analyzed via tandem quadrupole GS-MS/MS, combined with questionnaire data from the AESOP Study. Dietary exposure was modeled using Canadian Total Diet Survey PCB concentrations and National Health and Nutrition Examination Survey (NHANES) food ingestion rates. For ∑PCB, dietary exposure dominates. For individual lower-chlorinated congeners (e.g., PCBs 40+41+71, 52), inhalation exposure was as high as one-third of the total (dietary+inhalation) exposure. ∑PCB inhalation (geometric mean (SE)) was greater for urban mothers (7.1 (1.2) μg yr–1) and children (12.0 (1.2) μg yr–1) than for rural mothers (2.4 (0.4) μg yr–1) and children (8.9 (0.3) μg yr–1). Schools attended by AESOP Study children had higher indoor PCB concentrations than did homes, and account for the majority of children’s inhalation exposure. PMID:25510359

  13. Metabolite profiles of rats in repeated dose toxicological studies after oral and inhalative exposure.

    PubMed

    Fabian, E; Bordag, N; Herold, M; Kamp, H; Krennrich, G; Looser, R; Ma-Hock, L; Mellert, W; Montoya, G; Peter, E; Prokudin, A; Spitzer, M; Strauss, V; Walk, T; Zbranek, R; van Ravenzwaay, B

    2016-07-25

    The MetaMap(®)-Tox database contains plasma-metabolome and toxicity data of rats obtained from oral administration of 550 reference compounds following a standardized adapted OECD 407 protocol. Here, metabolic profiles for aniline (A), chloroform (CL), ethylbenzene (EB), 2-methoxyethanol (ME), N,N-dimethylformamide (DMF) and tetrahydrofurane (THF), dosed inhalatively for six hours/day, five days a week for 4 weeks were compared to oral dosing performed daily for 4 weeks. To investigate if the oral and inhalative metabolome would be comparable statistical analyses were performed. Best correlations for metabolome changes via both routes of exposure were observed for toxicants that induced profound metabolome changes. e.g. CL and ME. Liver and testes were correctly identified as target organs. In contrast, route of exposure dependent differences in metabolic profiles were noted for low profile strength e.g. female rats dosed inhalatively with A or THF. Taken together, the current investigations demonstrate that plasma metabolome changes are generally comparable for systemic effects after oral and inhalation exposure. Differences may result from kinetics and first pass effects. For compounds inducing only weak changes, the differences between both routes of exposure are visible in the metabolome.

  14. Cadmium as a respiratory toxicant

    SciTech Connect

    Grose, E.C.; Graham, J.A.

    1987-01-01

    Cadmium is a major respiratory toxicant as evidenced by numerous human and animal studies. Controlled animal inhalation studies provide supporting evidence to the associations observed in epidemiological studies that Cd has the potential to cause lung fibrosis, emphysema, cancer, and kidney disease after prolonged exposure. Shorter-term exposure studies indicate that mechanisms thought to be involved in several of these chronic disease states (especially fibrosis and emphysema) are acutely activated. The evidence of toxicity is sufficiently clear that a TLV has been set and the International Agency for Research on Cancer has named Cd as a Group B1 substance (probable human carcinogen). The risk to Cd exposure is enhanced by its chemical and physical properties that result in bioaccumulation. Thus, even a low-level exposure over long periods of time would be expected to reach doses that could be toxic.

  15. [Physio-pathological impacts of inhaled nanoparticles].

    PubMed

    Baeza-Squiban, Armelle

    2014-01-01

    Nanomaterials are defined as materials with any external dimension in the nanoscale or having an internal structure or surface structure in the nanoscale, approximately 1 nm to 100 nm. They exhibit new or reinforced properties as compared to the same material at the micrometric scale, providing a benefit in numerous technological applications. However, their specific surface properties in addition to their shape, composition, size are suspected to elicit adverse responses from biological systems, underlining the need for a thorough hazard assessment. Increasing use of nanomaterials in industrial as well as consumer products extends the possibilities of environmental and occupational human exposures. During all their life cycle, from their production to their destruction through their use, engineered nanoparticles can be released and the respiratory route is one of the main unintentional routes of exposure. Although the respiratory tract is equipped with efficient clearance mechanisms, there is increasing evidence that nanoparticles exhibit an ability to cross biological barriers, getting access to the bloodstream and secondary target organs. Different features of nanomaterials (size, form, surface reactivity...) contribute to their internalization and translocation through the respiratory barrier. Short term inhalation exposure to nanoparticles induces pulmonary inflammation the extent of which is dependent on the type of nanoparticles according to shape, size, solubility...Oxidative stress is considered as a major toxicity pathway triggered by nanomaterials as they can intrinsically produce reactive oxygen species or induced the intracellular production of reactive oxygen species or anti-oxidant depletion upon interaction with cells. Alternative mechanisms are suspected, related to the ability of nanoparticles to interact with proteins. As they get in contact with biological fluids, nanoparticles are covered by a protein corona that modifies their interactions

  16. Particle inhalability at low wind speeds.

    PubMed

    Brown, James S

    2005-12-15

    Accurate quantification of the dose delivered by aerosol exposures is essential for estimating the risk of potential adverse health effects. The fraction of airborne particles that can enter the nose or mouth during inhalation is referred to as the inspirable particulate mass fraction. This inhalable fraction is equivalent to delivered dose for particles greater than approximately 25 microm (aerodynamic particle diameter, d(ae)), which deposit completely and almost exclusively in the extrathoracic airways. Particle inhalability at high wind speeds (1-9 m/s) has been well characterized. However, there is a paucity of data describing the inhalability of particles at low wind speeds (< or =0.3 m/s), which are typical of indoor environments. High-wind-speed criteria poorly describe inhalability at low wind speeds. Based on the aspiration efficiencies of blunt and sharp-edged inlets, a function was developed for oral inhalability, P(I(O)), of particles at low wind speeds. This function predicts a slow decline in P(I(O)) from 0.95 at d(ae)= 8 microm, to 0.5 at d(ae) = 74 microm, and 0.1 at d(ae)= 175 microm. Data available from the literature for inhalability at relatively low wind speeds during oral breathing are well described by this logistic function (r(2)= 0.69).

  17. Dynamics of airflow in a short inhalation

    PubMed Central

    Bates, A. J.; Doorly, D. J.; Cetto, R.; Calmet, H.; Gambaruto, A. M.; Tolley, N. S.; Houzeaux, G.; Schroter, R. C.

    2015-01-01

    During a rapid inhalation, such as a sniff, the flow in the airways accelerates and decays quickly. The consequences for flow development and convective transport of an inhaled gas were investigated in a subject geometry extending from the nose to the bronchi. The progress of flow transition and the advance of an inhaled non-absorbed gas were determined using highly resolved simulations of a sniff 0.5 s long, 1 l s−1 peak flow, 364 ml inhaled volume. In the nose, the distribution of airflow evolved through three phases: (i) an initial transient of about 50 ms, roughly the filling time for a nasal volume, (ii) quasi-equilibrium over the majority of the inhalation, and (iii) a terminating phase. Flow transition commenced in the supraglottic region within 20 ms, resulting in large-amplitude fluctuations persisting throughout the inhalation; in the nose, fluctuations that arose nearer peak flow were of much reduced intensity and diminished in the flow decay phase. Measures of gas concentration showed non-uniform build-up and wash-out of the inhaled gas in the nose. At the carina, the form of the temporal concentration profile reflected both shear dispersion and airway filling defects owing to recirculation regions. PMID:25551147

  18. Inhalation challenge in humidifier fever.

    PubMed

    Edwards, J H; Cockcroft, A

    1981-05-01

    When exposed to an amount of contaminated humidifier water roughly equivalent to that inhaled over an 8-hour period at their work place, four out of six subjects developed symptoms of humidifier fever. Two non-exposed subjects failed to react to the same challenge. Characteristic lung function, temperature and leucocyte changes were recorded; however, a fall in gas transfer previously reported was not seen. That the reaction was immunologically mediated and not due to endotoxin activity was shown by a negative pyrogen response in rabbits inoculated intravenously with concentrated humidifier water. The nature of the immune response has not as yet been evaluated but it does not reside with the ability of humidifier fever antigens to activate complement. Skin testing produced an immediate weal and flare in the four subjects with precipitins and may reflect the presence of short-term anaphylactic IgG antibody.

  19. Inhaled Corticosteroids and Bone Health

    PubMed Central

    Chee, Carolyn; Sellahewa, Luckni; Pappachan, Joseph M

    2014-01-01

    Inhaled corticosteroids (ICS) are the cornerstones in the management of bronchial asthma and some cases of chronic obstructive pulmonary disease. Although ICS are claimed to have low side effect profiles, at high doses they can cause systemic adverse effects including bone diseases such as osteopenia, osteoporosis and osteonecrosis. Corticosteroids have detrimental effects on function and survival of osteoblasts and osteocytes, and with the prolongation of osteoclast survival, induce metabolic bone disease. Glucocorticoid-induced osteoporosis (GIO) can be associated with major complications such as vertebral and neck of femur fractures. The American College of Rheumatology (ACR) published criteria in 2010 for the management of GIO. ACR recommends bisphosphonates along with calcium and vitamin D supplements as the first-line agents for GIO management. ACR recommendations can be applied to manage patients on ICS with a high risk of developing metabolic bone disease. This review outlines the mechanisms and management of ICS-induced bone disease. PMID:25674178

  20. Pulmonary Toxicity Studies of Lunar Dusts in Rodents

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-wing; James, John T.; Taylor, Larry

    2008-01-01

    NASA will build an outpost on the lunar surface for long-duration human habitation and research. The surface of the Moon is covered by a layer of fine, reactive dust, and the living quarters in the lunar outpost are expected to be contaminated by lunar dust. NASA established the Lunar Airborne Dust Toxicity Advisory Group (LADTAG) to evaluate the risk of exposure to the dust and to establish safe exposure limits for astronauts working in the lunar habitat. Because the toxicity of lunar dust is not known, LADTAG has recommended investigating its toxicity in the lungs of laboratory animals. After receiving this recommendation, NASA directed the JSC Toxicology Laboratory to determine the pulmonary toxicity of lunar dust in exposed rodents. The rodent pulmonary toxicity studies proposed here are the same as those proposed by the LADTAG. Studies of the pulmonary toxicity of a dust are generally done first in rodents by intratracheal instillation (ITI). This toxicity screening test is then followed by an inhalation study, which requires much more of the test dust and is labor intensive. We succeeded in completing an ITI study on JSC-1 lunar dust simulant in mice (Lam et al., Inhalation Toxicology 14:901-916, 2002, and Inhalation Toxicology 14: 917-928, 2002), and have conducted a pilot ITI study to examine the acute toxicity of an Apollo lunar (highland) dust sample. Preliminary results obtained by examining lung lavage fluid from dust-treated mice show that lunar dust was somewhat toxic (more toxic than TiO2, but less than quartz dust). More extensive studies have been planned to further examine lung lavage fluid for biomarkers of toxicity and lung tissues for histopathological lesions in rodents exposed to aged and activated lunar dust samples. In these studies, reference dusts (TiO2 and quartz) of known toxicities and have industrial exposure limits will be studied in parallel so the relative toxicity of lunar dust can be determined. The ITI results will also be