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Sample records for acceptable toxicity profile

  1. Consumer acceptance and sensory profiling of reengineered kitoza products.

    PubMed

    Pintado, Ana I E; Monteiro, Maria J P; Talon, Régine; Leroy, Sabine; Scislowski, Valérie; Fliedel, Geneviève; Rakoto, Danielle; Maraval, Isabelle; Costa, Ana I A; Silva, Ana P; Pallet, Dominique; Tomlins, Keith; Pintado, Manuela M E

    2016-05-01

    Kitoza refers to a traditional way of preparing beef and pork in Madagascar. However, in order to improve some drawbacks previous identified, the product was submitted to a reengineering process. The acceptance and sensory profiling of improved Kitoza products among Portuguese consumers was investigated. A local smoked loin sausage was selected as basis for comparison. Firstly, a Focus Group study was performed to identify sensory descriptors for Kitoza products and explore product perception. Subsequently, a Flash Profile and a consumer sensory acceptance study were conducted. Flash Profile's results showed that beef- and pork-based Kitoza products investigated differed considerably in all sensory dimensions. The Portuguese sausage was characterized as having a more intense and lasting after taste, as well as displaying a higher degree of (meat) doneness. The acceptance study yielded higher overall liking ratings for pork- than for beef-based Kitoza, although the Portuguese sausage remained the most appreciated product. PMID:26769507

  2. GENE EXPRESSION PROFILING TO IDENTIFY BIOMARKERS OF REPRODUCTIVE TOXICITY

    EPA Science Inventory

    SOT 2005 SESSION ABSTRACT

    GENE EXPRESSION PROFILING TO IDENTIFY BIOMARKERS OF REPRODUCTIVE TOXICITY

    David J. Dix. National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle...

  3. Development of an in Silico Profiler for Mitochondrial Toxicity.

    PubMed

    Nelms, Mark D; Mellor, Claire L; Cronin, Mark T D; Madden, Judith C; Enoch, Steven J

    2015-10-19

    This study outlines the analysis of mitochondrial toxicity for a variety of pharmaceutical drugs extracted from Zhang et al. ((2009) Toxicol. In Vitro, 23, 134-140). These chemicals were grouped into categories based upon structural similarity. Subsequently, mechanistic analysis was undertaken for each category to identify the molecular initiating event driving mitochondrial toxicity. The mechanistic information elucidated during the analysis enabled mechanism-based structural alerts to be developed and combined together to form an in silico profiler. This profiler is envisaged to be used to develop chemical categories based upon similar mechanisms as part of the adverse outcome pathway paradigm. Additionally, the profiler could be utilized in screening large data sets in order to identify chemicals with the potential to induce mitochondrial toxicity. PMID:26375963

  4. GENE EXPRESSION PROFILING TO IDENTIFY MECHANISMS OF MALE REPRODUCTIVE TOXICITY

    EPA Science Inventory

    Gene Expression Profiling to Identify Mechanisms of Male Reproductive Toxicity
    David J. Dix
    National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, 27711, USA.
    Ab...

  5. Pathway Profiling and Tissue Modeling of Developmental Toxicity

    EPA Science Inventory

    High-throughput and high-content screening (HTS-HCS) studies are providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential toxicity. EPA’s ToxCast™ project, and the broader Tox21 consortium, in addition t...

  6. A Review on Renal Toxicity Profile of Common Abusive Drugs

    PubMed Central

    Singh, Varun Parkash; Singh, Nirmal

    2013-01-01

    Drug abuse has become a major social problem of the modern world and majority of these abusive drugs or their metabolites are excreted through the kidneys and, thus, the renal complications of these drugs are very common. Morphine, heroin, cocaine, nicotine and alcohol are the most commonly abused drugs, and their use is associated with various types of renal toxicity. The renal complications include a wide range of glomerular, interstitial and vascular diseases leading to acute or chronic renal failure. The present review discusses the renal toxicity profile and possible mechanisms of commonly abused drugs including morphine, heroin, cocaine, nicotine, caffeine and alcohol. PMID:23946695

  7. Acceptable Toxicity After Stereotactic Body Radiation Therapy for Liver Tumors Adjacent to the Central Biliary System

    SciTech Connect

    Eriguchi, Takahisa; Takeda, Atsuya; Sanuki, Naoko; Oku, Yohei; Aoki, Yousuke; Shigematsu, Naoyuki; Kunieda, Etsuo

    2013-03-15

    Purpose: To evaluate biliary toxicity after stereotactic body radiation therapy (SBRT) for liver tumors. Methods and Materials: Among 297 consecutive patients with liver tumors treated with SBRT of 35 to 50 Gy in 5 fractions, patients who were irradiated with >20 Gy to the central biliary system (CBS), including the gallbladder, and had follow-up times >6 months were retrospectively analyzed. Toxicity profiles, such as clinical symptoms and laboratory and radiologic data especially for obstructive jaundice and biliary infection, were investigated in relation to the dose volume and length relationship for each biliary organ. Results: Fifty patients with 55 tumors were irradiated with >20 Gy to the CBS. The median follow-up period was 18.2 months (range, 6.0-80.5 months). In the dose length analysis, 39, 34, 14, and 2 patients were irradiated with >20 Gy, >30 Gy, >40 Gy, and >50 Gy, respectively, to >1 cm of the biliary tract. Seven patients were irradiated with >20 Gy to >20% of the gallbladder. Only 2 patients experienced asymptomatic bile duct stenosis. One patient, metachronously treated twice with SBRT for tumors adjacent to each other, had a transient increase in hepatic and biliary enzymes 12 months after the second treatment. The high-dose area >80 Gy corresponded to the biliary stenosis region. The other patient experienced biliary stenosis 5 months after SBRT and had no laboratory changes. The biliary tract irradiated with >20 Gy was 7 mm and did not correspond to the bile duct stenosis region. No obstructive jaundice or biliary infection was found in any patient. Conclusions: SBRT for liver tumors adjacent to the CBS was feasible with minimal biliary toxicity. Only 1 patient had exceptional radiation-induced bile duct stenosis. For liver tumors adjacent to the CBS without other effective treatment options, SBRT at a dose of 40 Gy in 5 fractions is a safe treatment with regard to biliary toxicity.

  8. Passion fruit juice with different sweeteners: sensory profile by descriptive analysis and acceptance

    PubMed Central

    Rocha, Izabela Furtado de Oliveira; Bolini, Helena Maria André

    2015-01-01

    This study evaluated the effect of different sweeteners on the sensory profile, acceptance, and drivers of preference of passion fruit juice samples sweetened with sucrose, aspartame, sucralose, stevia, cyclamate/saccharin blend 2:1, and neotame. Sensory profiling was performed by 12 trained assessors using quantitative descriptive analysis (QDA). Acceptance tests (appearance, aroma, flavor, texture and overall impression) were performed with 124 consumers of tropical fruit juice. Samples with sucrose, aspartame and sucralose showed similar sensory profile (P < 0.05), without bitter taste, bitter aftertaste, and metallic taste, and samples with sucrose and sucralose did not differ from each other for the attribute sweet aftertaste. Passion fruit flavor affected positively and sweet aftertaste affected negatively the acceptance of the samples. Samples sweetened with aspartame, sucralose, and sucrose presented higher acceptance scores for the attributes flavor, texture, and overall impression, with no significant (P < 0.05) differences between them. Aspartame and sucralose can be good substitutes for sucrose in passion fruit juice. PMID:25838891

  9. Passion fruit juice with different sweeteners: sensory profile by descriptive analysis and acceptance.

    PubMed

    Rocha, Izabela Furtado de Oliveira; Bolini, Helena Maria André

    2015-03-01

    This study evaluated the effect of different sweeteners on the sensory profile, acceptance, and drivers of preference of passion fruit juice samples sweetened with sucrose, aspartame, sucralose, stevia, cyclamate/saccharin blend 2:1, and neotame. Sensory profiling was performed by 12 trained assessors using quantitative descriptive analysis (QDA). Acceptance tests (appearance, aroma, flavor, texture and overall impression) were performed with 124 consumers of tropical fruit juice. Samples with sucrose, aspartame and sucralose showed similar sensory profile (P < 0.05), without bitter taste, bitter aftertaste, and metallic taste, and samples with sucrose and sucralose did not differ from each other for the attribute sweet aftertaste. Passion fruit flavor affected positively and sweet aftertaste affected negatively the acceptance of the samples. Samples sweetened with aspartame, sucralose, and sucrose presented higher acceptance scores for the attributes flavor, texture, and overall impression, with no significant (P < 0.05) differences between them. Aspartame and sucralose can be good substitutes for sucrose in passion fruit juice. PMID:25838891

  10. Gaining acceptance for the use of in vitro toxicity assays and QIVIVE in regulatory risk assessment.

    PubMed

    Meek, M E Bette; Lipscomb, John C

    2015-06-01

    Testing strategies are anticipated to increasingly rely on in vitro data as a basis to characterize early steps or key events in toxicity at relevant dose levels in human tissues. Such strategies require quantitative in vitro to in vivo extrapolation to characterize dose-response as a basis for comparison with exposure to estimate risk. Current experience in the incorporation of mechanistic and in vitro data in risk assessment is considered here in the context of identified principles to increase the potential for timely acceptance of more progressive and tailored testing strategies by the regulatory community. These principles are outlined as transitioning in a familiar context, tiering to acquire experience and increase confidence, contextual knowledge transfer to facilitate interpretation and communication, coordination and development of expertise and continuing challenge. A proposed pragmatic tiered data driven framework which includes increasing reliance on in vitro data and quantitative in vitro to in vivo extrapolation is considered in the context of these principles. Based on this analysis, possible additional steps that might facilitate timely evolution and potentially, uptake are identified. PMID:25598226

  11. Rectal toxicity profile after transperineal interstitial permanent prostate brachytherapy: Use of a comprehensive toxicity scoring system and identification of rectal dosimetric toxicity predictors

    SciTech Connect

    Shah, Jinesh N.; Ennis, Ronald D. . E-mail: rennis@chpnet.org

    2006-03-01

    Purpose: To better understand rectal toxicity after prostate brachytherapy, we employed the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0), a comprehensive system with distinct and separately reported gastrointestinal adverse event items (unlike Radiation Therapy Oncology Group morbidity scoring), to evaluate item-specific postimplant rectal toxicities. Methods and Materials: We analyzed 135 patients treated with brachytherapy {+-} hormonal therapy, using CTCAE v3.0 to score acute/late rectal toxicities (median follow-up, 41 months). Dosimetric parameters were evaluated for ability to predict toxicities. Results: Use of CTCAE yielded a novel rectal toxicity profile consisting of diarrhea, incontinence, urgency, proctitis, pain, spasms, and hemorrhage event rates. No item had a <5% Grade 1-2 acute toxicity rate (except spasms). Rectal dosimetry predicted late toxicities: for diarrhea, 5% Grade 1 toxicity rate for %V{sub 25} (percent of rectal volume receiving 25% of prescribed prostate dose) {<=} 25% vs. 60% for %V{sub 25} > 25% (p < 0.001); for maximum toxicity, 10% Grade 1 toxicity rate for %V{sub 1} {<=} 40% vs. 44% for %V{sub 1} > 40% (p = 0.007). Conclusions: A comprehensive understanding of item-specific postimplant rectal toxicities was obtained using CTCAE. Rectal %V{sub 25} > 25% and %V{sub 1} > 40% predicted worse late diarrhea and maximum toxicity, respectively.

  12. Evaluation of drug toxicity profiles based on the phenotypes of ascidian Ciona intestinalis.

    PubMed

    Mizotani, Yuji; Itoh, Shun; Hotta, Kohji; Tashiro, Etsu; Oka, Kotaro; Imoto, Masaya

    2015-08-01

    In vivo toxicity evaluation using model organisms is an important step for the development of new drugs. Here, we report that Ciona intestinalis, a chordate invertebrate, is beneficial to drug toxicity evaluation for the following reasons: rapid embryonic and larval development, resemblance to vertebrates, ease of management, low cost, transparent body, and low risk of ethical issues. The dynamic phenotypic change of Ciona larvae during metamorphosis prompted us to examine the effect of cytotoxic drugs on its development by quantifying six toxicity endpoints: degenerated tail size, ampulla length, rotation of body axis, stomach size, heart rate, and body size. As a result, mitochondrial respiratory inhibitors, tubulin polymerization/depolymerization inhibitors, or DNA/RNA synthesis inhibitors showed distinct toxicity profiles against these six endpoints, but drugs with the same targets showed a similar toxicity profile in Ciona. Our results suggest Ciona is an effective animal model for profiling drug toxicity and exploring the mechanisms of drugs with unknown targets. PMID:26043689

  13. Profiling Animal Toxicants by Automatically Mining Public Bioassay Data: A Big Data Approach for Computational Toxicology

    PubMed Central

    Zhang, Jun; Hsieh, Jui-Hua; Zhu, Hao

    2014-01-01

    In vitro bioassays have been developed and are currently being evaluated as potential alternatives to traditional animal toxicity models. Already, the progress of high throughput screening techniques has resulted in an enormous amount of publicly available bioassay data having been generated for a large collection of compounds. When a compound is tested using a collection of various bioassays, all the testing results can be considered as providing a unique bio-profile for this compound, which records the responses induced when the compound interacts with different cellular systems or biological targets. Profiling compounds of environmental or pharmaceutical interest using useful toxicity bioassay data is a promising method to study complex animal toxicity. In this study, we developed an automatic virtual profiling tool to evaluate potential animal toxicants. First, we automatically acquired all PubChem bioassay data for a set of 4,841 compounds with publicly available rat acute toxicity results. Next, we developed a scoring system to evaluate the relevance between these extracted bioassays and animal acute toxicity. Finally, the top ranked bioassays were selected to profile the compounds of interest. The resulting response profiles proved to be useful to prioritize untested compounds for their animal toxicity potentials and form a potential in vitro toxicity testing panel. The protocol developed in this study could be combined with structure-activity approaches and used to explore additional publicly available bioassay datasets for modeling a broader range of animal toxicities. PMID:24950175

  14. Profiling the reproductive toxicity of chemicals from multigeneration studies in the toxicity reference database

    EPA Science Inventory

    Multigeneration reproduction studies are used to characterize parental and offspring systemic toxicity, as well as reproductive toxicity of pesticides, industrial chemicals and pharmaceuticals. Results from 329 multigeneration studies on 316 chemicals have been digitized into sta...

  15. Evaluation of three soil toxicity tests used to monitor acceptable endpoints

    SciTech Connect

    Brinkmann, M.; Stroo, H.; Leuschner, A.; Leuteritz, D.; Stromberg, M.; Brourman, M.

    1995-12-31

    Three terrestrial toxicity tests were used to evaluate the efficacy of biological treatment of creosote and pentachlorophenol impacted soils at a Superfund site. Microtox, 5-day lettuce seed, and 14-day earthworm toxicity tests were performed on 10 soil samples at the beginning and end of 3 months of land treatment. Secondary endpoints of root length and earthworm weight loss were also evaluated. EC50 and LC50 values were calculated using a Trimmed Logit Statistical Program and compared to toxicity of 10 background samples collected from the site. Results for initial soils demonstrated toxicity with three of the five endpoints. End treatment results showed no measurable toxicity using all endpoints. Toxicity testing results are critical for obtaining regulatory approval for the full-scale treatment system. Post treatment closure requirements for the site will be based on bioassay results. Evaluation of the three tests used showed the Microtox test to be the most sensitive to this type of toxicity. Lettuce seed germination results were the least sensitive of the three primary endpoints chosen. Of the secondary endpoint criteria, root length demonstrated reliable EC50 values and showed toxicity trends similar to Microtox and earthworm tests. The earthworm weight loss endpoint was not a useful toxicity measurement at 14 days.

  16. ACTIVITY PROFILES OF DEVELOPMENTAL TOXICITY: DESIGN CONSIDERATIONS AND PILOT IMPLEMENTATION

    EPA Science Inventory

    The available literature was searched for quantitative test results from both in vitro and in vivo assays for developmental toxicity for five model compounds: yclophosphamid, methotrexate, hydroxyurea, caffeine, and ethylenethiourea. hese compounds were chosen on the basis of the...

  17. KSC 50-MHz Doppler Radar Wind Profiler (DRWP) Operational Acceptance Test (OAT) Report

    NASA Technical Reports Server (NTRS)

    Barbre, Robert E.

    2015-01-01

    This report documents analysis results of the Kennedy Space Center updated 50-MHz Doppler Radar Wind Profiler (DRWP) Operational Acceptance Test (OAT). This test was designed to demonstrate that the new DRWP operates in a similar manner to the previous DRWP for use as a situational awareness asset for mission operations at the Eastern Range to identify rapid changes in the wind environment that weather balloons cannot depict. Data examination and two analyses showed that the updated DRWP meets the specifications in the OAT test plan and performs at least as well as the previous DRWP. Data examination verified that the DRWP provides complete profiles every five minutes from 1.8-19.5 km in vertical increments of 150 m. Analysis of 5,426 wind component reports from 49 concurrent DRWP and balloon profiles presented root mean square (RMS) wind component differences around 2.0 m/s. The DRWP's effective vertical resolution (EVR) was found to be 300 m for both the westerly and southerly wind component, which the best EVR possible given the DRWP's vertical sampling interval. A third analysis quantified the sensitivity to rejecting data that do not have adequate signal by assessing the number of first-guess propagations at each altitude. This report documents the data, quality control procedures, methodology, and results of each analysis. It also shows that analysis of the updated DRWP produced results that were at least as good as the previous DRWP with proper rationale. The report recommends acceptance of the updated DRWP for situational awareness usage as per the OAT's intent.

  18. Results of the NASA Kennedy Space Center 50-MHz Doppler Radar Wind Profiler Operational Acceptance Test

    NASA Technical Reports Server (NTRS)

    Barbre', Robert E., Jr.; Decker, Ryan K.; Leahy, Frank B.; Huddleston, Lisa

    2016-01-01

    This paper presents results of the new Kennedy Space Center (KSC) 50-MHz Doppler Radar Wind Profiler (DRWP) Operational Acceptance Test (OAT). The goal of the OAT was to verify the data quality of the new DRWP against the performance of the previous DRWP in order to use wind data derived by the new DRWP for space launch vehicle operations support at the Eastern Range. The previous DRWP was used as a situational awareness asset for mission operations to identify rapid changes in the wind environment that weather balloons cannot depict. The Marshall Space Flight Center's Natural Environments Branch assessed data from the new DRWP collected during Jan-Feb 2015 against a specified set of test criteria. Data examination verified that the DRWP provides complete profiles every five minutes from 1.8-19.5 km in vertical increments of 150 m. Analysis of 49 concurrent DRWP and balloon profiles presented root mean square wind component differences around 2.0 m/s. Evaluation of the DRWP's coherence between five-minute wind pairs found the effective vertical resolution to be Nyquist-limited at 300 m for both wind components. In addition, the sensitivity to rejecting data that do not have adequate signal was quantified. This paper documents the data, quality control procedures, methodology, and results of each analysis.

  19. PEER REVIEW OF THE PERSISTENT, BIOACCUMULATIVE, AND TOXIC (PBT) PROFILER

    EPA Science Inventory

    The U.S. EPA is required, under Sections 4, 5, and 6 of the Toxic Substances Control Act (TSCA), to screen chemicals for potential risk to humans and the environment. OPPT has developed computerized methods designed to support screening-level assessment of chemicals in the absen...

  20. Elucidation of Adverse Bioactivity Profiles as Predictors of Toxicity Potential

    EPA Science Inventory

    Toxicity testing in vitro remains a formidable challenge due to lack of understanding of key molecular targets and pathways underlying many pathological events. The combination of genome sequencing and widespread application of high-throughput screening tools have provided the me...

  1. Gaining Acceptance for the use of in vitro Toxicity Assays and QIVIVE in Regulatory Risk Assessment

    EPA Science Inventory

    Testing strategies are anticipated to increasingly rely on in vitro data as a basis to characterize early steps or key events in toxicity at relevant dose levels in human tissues. This requires quantitative in vitro to in vivo extrapolation to characterize dose-response as a bas...

  2. Validation, acceptance, and extension of a predictive model of reproductive toxicity using ToxCast data

    EPA Science Inventory

    The EPA ToxCast research program uses a high-throughput screening (HTS) approach for predicting the toxicity of large numbers of chemicals. Phase-I tested 309 well-characterized chemicals (mostly pesticides) in over 500 assays of different molecular targets, cellular responses an...

  3. Short communication: Sensory profile and acceptability of a cow milk cheese manufactured by adding jenny milk.

    PubMed

    Cosentino, C; Faraone, D; Paolino, R; Freschi, P; Musto, M

    2016-01-01

    The addition of jenny milk during cheesemaking has been recommended as a viable alternative to egg lysozyme for controlling late blowing defects. However, little is known on the sensory properties of the cheeses made with jenny milk. In this study, the effect of the addition of jenny milk during cheesemaking on sensory properties and consumer acceptability of cheese was evaluated. A sensory profile was carried out by 10 trained panelists on 4 cow milk cheese types. Two types of cheeses were made by adding jenny milk to cow milk during cheesemaking; the cheeses were then left to ripen for 45 and 120 d. The remaining 2 cheese types were made with only cow milk and were also left to ripen for 45 and 120 d. The attributes generated by a quantitative descriptive analysis sensory panel were effective for discriminating the 4 products. Among them, added jenny milk samples aged for 45 d had the highest intensity of some appearance descriptors (structure and color uniformity), as well as the highest intensity of sweetness. The analysis of acceptability data obtained from 89 consumers showed that added jenny milk aged for 45 d was the most preferred type of cheese, whereas no significant differences were found among the other products, which had higher intensity of bitter, salty, acid milk, and so on. PMID:26506544

  4. Toxic chemical hazard classification and risk acceptance guidelines for use in DOE facilities. Revision 2

    SciTech Connect

    Craig, D.K.; Davis, J.S.; Prowse, J.; Hoffman, P.W.

    1995-03-24

    The concentration-limit guidelines presented in this document apply to airborne releases of chemicals evaluated with respect to human health effects for the purposes of hazard classification and categorization, risk assessment and safety analysis. They apply to all DOE facilities and operations involving the use of potentially hazardous chemicals. The guidelines do not address other nonradiological hazards such as fire, pressure releases (including explosions), and chemical reactivity, but the guidelines are applicable to hazardous chemical releases resulting from these events. This report presents the subcommittee`s evaluation and recommendations regarding analyses of accidentally released toxic chemicals. The premise upon which these recommendations are based is that the mechanism of action of toxic chemicals is fundamentally different from that associated with radionuclides, with the exception of carcinogens. The recommendations reported herein are restricted to the airborne pathway because in an accident scenario this typically represents the most immediately significant route of public exposure. However, the subcommittee recognizes that exposure to chemicals through other pathways, in particular waterborne, can have significant impacts on human health and the environment. Although there are a number of chemicals for which absorption through the skin can contribute measurably to the total dose in chronic (e.g., occupational) exposure situations, this pathway has not been considered for the acute exposure scenarios considered in this report. Later studies. will address these issues if it appears desirable.

  5. Subacute Toxicity Profile of Lacidipine Nanoformulation in Wistar Rats

    PubMed Central

    Shirodkar, Rupesh; Misra, Chandrasekhar; GH, Chethan; Shetty, Pallavi; Mutalik, Srinivas; Lewis, Shaila

    2015-01-01

    The present study was aimed at investigating the safety of Lacidipine (LCDP) loaded nanostructured lipid carriers (NLCs) in Wistar rats. NLCs were formulated using ultrasound dispersion technique. Animals were orally treated once daily with NLCs containing 0.140 mg, 0.350 mg, and 0.875 mg of LCDP as low, medium, and high dose per kg body weight, respectively, during 28 days along with blank formulation and pure LCDP. Control rats were fed with water. Animals were observed throughout experiment period and their body weight was recorded once weekly. Overnight fasted rats were sacrificed on the 29th day. Study revealed no signs or symptoms of toxicity or morbidity. No significant changes in the body weight were observed between treated and control group. Significant increase in left testis weight and liver weight was observed in male and female rats, respectively. Haematological estimation revealed significant decrease in haemoglobin count in male rats while female rats showed significant increase in granulocyte count. All the serum clinical parameters were within the normal range and no gross histopathological changes were observed. No delayed effect was noted in satellite group. The results indicate that developed LCDP loaded NLCs are safe when administered orally in rats. PMID:26101786

  6. Proposal of an in silico profiler for categorisation of repeat dose toxicity data of hair dyes.

    PubMed

    Nelms, M D; Ates, G; Madden, J C; Vinken, M; Cronin, M T D; Rogiers, V; Enoch, S J

    2015-05-01

    This study outlines the analysis of 94 chemicals with repeat dose toxicity data taken from Scientific Committee on Consumer Safety opinions for commonly used hair dyes in the European Union. Structural similarity was applied to group these chemicals into categories. Subsequent mechanistic analysis suggested that toxicity to mitochondria is potentially a key driver of repeat dose toxicity for chemicals within each of the categories. The mechanistic hypothesis allowed for an in silico profiler consisting of four mechanism-based structural alerts to be proposed. These structural alerts related to a number of important chemical classes such as quinones, anthraquinones, substituted nitrobenzenes and aromatic azos. This in silico profiler is intended for grouping chemicals into mechanism-based categories within the adverse outcome pathway paradigm. PMID:24888375

  7. Behavioural toxicity assessment of silver ions and nanoparticles on zebrafish using a locomotion profiling approach.

    PubMed

    Ašmonaitė, Giedrė; Boyer, Scott; Souza, Karine Bresolin de; Wassmur, Britt; Sturve, Joachim

    2016-04-01

    Zebrafish (Danio rerio) is not only a widely used species in the Fish Embryo Toxicity (FET) test but also an emerging model in behavioural ecotoxicology. By using automatic behaviour tracking technology, locomotion of developing zebrafish (ZF) larvae can be accurately recorded and potentially used in an ecotoxicological context to detect toxicant-induced behavioural alterations. In this study, we explored if and how quantitative locomotion data can be used for sub-lethal toxicity testing within the FET framework. We exposed ZF embryos to silver ions and nanoparticles, which previously have been reported to cause neurodevelopmental toxicity and behavioural retardation in early-life stages of ZF. Exposure to a broad range of silver (Ag(+) and AgNPs) concentrations was conducted, and developmental toxicity was assessed using FET criteria. For behavioural toxicity assessment, locomotion of exposed ZF eleutheroembryos (120hpf) was quantified according to a customised behavioural assay in an automatic video tracking system. A set of repeated episodes of dark/light stimulation were used to artificially stress ZF and evoke photo-motor responses, which were consequently utilized for locomotion profiling. Our locomotion-based behaviour profiling approach consisted of (1) dose-response ranking for multiple and single locomotion variables; (2) quantitative assessment of locomotion structure; and (3) analysis of ZF responsiveness to darkness stimulation. We documented that both silver forms caused adverse effects on development and inhibited hatchability and, most importantly, altered locomotion. High Ag(+) and AgNPs exposures significantly suppressed locomotion and a clear shift in locomotion towards inactivity was reported. Additionally, we noted that low, environmentally relevant Ag(+) concentrations may cause subordinate locomotive changes (hyperactivity) in developing fish. Overall, it was concluded that our locomotion-based behaviour-testing scheme can be used jointly

  8. Hydroxyethyl starch and granulocyte transfusions: considerations of utility and toxicity profile for patients and donors.

    PubMed

    Ambruso, Daniel R

    2015-04-01

    Hydroxyethyl starch (hetastarch) is a synthetic glucose compound with extensive clinical use as a volume expander. Because of its red blood cell-sedimenting properties, hetastarch plays a major role in preparation of granulocyte products. Recent concerns have been raised about the use of hetastarch in critically ill patients for the development of renal injury and other severe adverse events. In contrast, granulocyte donors receive much less of this compound during collection procedures, and over many years, minimal toxicity has been documented in these individuals. Furthermore, granulocyte products contain very little hetastarch, and ill effects on renal function have not been associated with their administration. This review assesses available information about the toxicity profile of hetastarch in critically ill patients requiring a volume expander as well as granulocyte donors and recipients. Because of the lack of toxicity in these latter two groups, hetastarch should be available for preparation of granulocyte products and their administration. PMID:25315227

  9. Urinary and Rectal Toxicity Profiles After Permanent Iodine-125 Implant Brachytherapy in Japanese Men: Nationwide J-POPS Multi-institutional Prospective Cohort Study

    SciTech Connect

    Ohashi, Toshio; Yorozu, Atsunori; Saito, Shiro; Tanaka, Nobumichi; Katayama, Norihisa; Kojima, Shinsuke; Maruo, Shinichiro; Kikuchi, Takashi; Dokiya, Takushi; Fukushima, Masanori; Yamanaka, Hidetoshi

    2015-09-01

    Purpose: To assess, in a nationwide multi-institutional cohort study begun in 2005 and in which 6927 subjects were enrolled by 2010, the urinary and rectal toxicity profiles of subjects who enrolled during the first 2 years, and evaluate the toxicity profiles for permanent seed implantation (PI) and a combination therapy with PI and external beam radiation therapy (EBRT). Methods and Materials: Baseline data for 2339 subjects out of 2354 patients were available for the analyses. Toxicities were evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events, and the International Prostate Symptom Scores were recorded prospectively until 36 months after radiation therapy. Results: Grade 2+ acute urinary toxicities developed in 7.36% (172 of 2337) and grade 2+ acute rectal toxicities developed in 1.03% (24 of 2336) of the patients. Grade 2+ late urinary and rectal toxicities developed in 5.75% (133 of 2312) and 1.86% (43 of 2312) of the patients, respectively. A higher incidence of grade 2+ acute urinary toxicity occurred in the PI group than in the EBRT group (8.49% vs 3.66%; P<.01). Acute rectal toxicity outcomes were similar between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late urinary toxicities were 6.04% versus 4.82% for the PI and the EBRT groups, respectively, with no significant differences between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late rectal toxicities were 0.90% versus 5.01% (P<.01) for the PI and the EBRT groups, respectively. The mean of the postimplant International Prostate Symptom Score peaked at 3 months, but it decreased to a range that was within 2 points of the baseline score, which was observed in 1625 subjects (69.47%) at the 1-year follow-up assessment. Conclusions: The acute urinary toxicities observed were acceptable given the frequency and retention, and the late rectal toxicities were more favorable than those of other studies.

  10. Toxicity Profile of a Nutraceutical Formulation Derived from Green Mussel Perna viridis

    PubMed Central

    Joseph, Deepu; Chakkalakal, Selsa J.

    2014-01-01

    The short-term (acute) and long-term (subchronic) toxicity profile, mean lethal dose 50 (LD50), and no-observed-adverse-effect level (NOAEL) of a nutraceutical formulation developed from green mussel Perna viridis, which showed in vitro and in vivo anti-inflammatory properties, were evaluated in the present study. The formulation was administered to the male and female Wistar rats at graded doses (0.5, 1.0, and 2.5 g/kg body weight) for two weeks of acute toxicity study and 0.5, 1.0, and 2.0 g/kg body weight for 90 days in subchronic toxicity study. The LD50, variations in clinical signs, changes in body weight, body weight, food/water consumption, organ weight (liver, kidney, spleen, and brain), hematology, serum chemistry, and histopathological changes were evaluated. The LD50 of the formulation was 5,000 mg/kg BW. No test article related mortalities as well as change in body weight, and food and water consumption were observed. No toxicity related significant changes were noted in renal/hepatic function, hematological indices, and serum biochemical parameters between the control and treated groups. Histopathological alterations were not observed in the vital organs of rats. The subchronic NOAEL for the formulation in rats is greater than 2000 mg/kg. This study demonstrated that the green mussel formulation is safe to consume without any adverse effects in the body. PMID:24995298

  11. In Vitro and In Vivo Toxicity Profiling of Ammonium-Based Deep Eutectic Solvents

    PubMed Central

    Hayyan, Maan; Looi, Chung Yeng; Hayyan, Adeeb; Wong, Won Fen; Hashim, Mohd Ali

    2015-01-01

    The cytotoxic potential of ammonium-based deep eutectic solvents (DESs) with four hydrogen bond donors, namely glycerine (Gl), ethylene glycol (EG), triethylene glycol (TEG) and urea (U) were investigated. The toxicity of DESs was examined using In Vitro cell lines and In Vivo animal model. IC50 and selectivity index were determined for the DESs, their individual components and their combinations as aqueous solutions for comparison purposes. The cytotoxicity effect of DESs varied depending on cell lines. The IC50 for the GlDES, EGDES, UDES and TEGDES followed the sequence of TEGDES< GlDES< EGDES< UDES for OKF6, MCF-7, A375, HT29 and H413, respectively. GlDES was selective against MCF-7 and A375, EGDES was selective against MCF-7, PC3, HepG2 and HT29, UDES was selective against MCF-7, PC3, HepG2 and HT29, and TEGDES was selective against MCF-7 and A375. However, acute toxicity studies using ICR mice showed that these DESs were relatively toxic in comparison to their individual components. DES did not cause DNA damage, but it could enhance ROS production and induce apoptosis in treated cancer cells as evidenced by marked LDH release. Furthermore, the examined DESs showed less cytotoxicity compared with ionic liquids. To the best of our knowledge, this is the first time that combined In Vitro and In Vivo toxicity profiles of DESs were being demonstrated, raising the toxicity issue of these neoteric mixtures and their potential applicability to be used for therapeutic purposes. PMID:25679975

  12. In Vitro and In Vivo toxicity profiling of ammonium-based deep eutectic solvents.

    PubMed

    Hayyan, Maan; Looi, Chung Yeng; Hayyan, Adeeb; Wong, Won Fen; Hashim, Mohd Ali

    2015-01-01

    The cytotoxic potential of ammonium-based deep eutectic solvents (DESs) with four hydrogen bond donors, namely glycerine (Gl), ethylene glycol (EG), triethylene glycol (TEG) and urea (U) were investigated. The toxicity of DESs was examined using In Vitro cell lines and In Vivo animal model. IC50 and selectivity index were determined for the DESs, their individual components and their combinations as aqueous solutions for comparison purposes. The cytotoxicity effect of DESs varied depending on cell lines. The IC50 for the GlDES, EGDES, UDES and TEGDES followed the sequence of TEGDES< GlDES< EGDES< UDES for OKF6, MCF-7, A375, HT29 and H413, respectively. GlDES was selective against MCF-7 and A375, EGDES was selective against MCF-7, PC3, HepG2 and HT29, UDES was selective against MCF-7, PC3, HepG2 and HT29, and TEGDES was selective against MCF-7 and A375. However, acute toxicity studies using ICR mice showed that these DESs were relatively toxic in comparison to their individual components. DES did not cause DNA damage, but it could enhance ROS production and induce apoptosis in treated cancer cells as evidenced by marked LDH release. Furthermore, the examined DESs showed less cytotoxicity compared with ionic liquids. To the best of our knowledge, this is the first time that combined In Vitro and In Vivo toxicity profiles of DESs were being demonstrated, raising the toxicity issue of these neoteric mixtures and their potential applicability to be used for therapeutic purposes. PMID:25679975

  13. Haematolohical Profile of Subacute Oral Toxicity of Molybdenum and Ameliorative Efficacy of Copper Salt in Goats

    PubMed Central

    Kusum; Raina, R.; Verma, P. K.; Pankaj, N. K.; Kant, V.; Kumar, J.; Srivastava, A. K.

    2010-01-01

    Molybdenum toxicity produces a state of secondary hypocuprosis, resulting into alterations in normal hematological profile. In the present study, ammonium molybdate alone and with copper sulfate (II) pentahydrate (ameliorative agent) was administered orally for 30 consecutive days in healthy goats of group 1 and 2, respectively, to access the effect on the hematological profile on different predetermined days of dosing. Administration of ammonium molybdate alone produced significant decline in the mean values of hemoglobin (Hb), packed cell volume (PCV), total leukocyte count (TLC), total erythrocyte count (TEC), and mean corpuscular hemoglobin concentration (MCHC), with a significant increase in neutrophil level and mean corpuscular volume (MCV). However, values of erythrocyte sedimentation rate, mean corpuscular hemoglobin, and differential leukocyte count were not significantly altered. On comparing observations of ameliorative group with the group 1 goats, it is concluded that the ameliorative copper salt has beneficial effects in alleviating the alterations in the values of Hb, PCV, TLC, TEC, MCV, MCHC, and neutrophils. PMID:21170251

  14. Toxicity Profile of the Aqueous Ethanol Root Extract of Corrigiola telephiifolia Pourr. (Caryophyllaceae) in Rodents

    PubMed Central

    Lakmichi, Hind; Bakhtaoui, Fatima Zahra; Gadhi, Chemseddoha A.; Ezoubeiri, Aicha; El Jahiri, Younes; El Mansouri, Abdellah; Zrara, Ibtissam; Loutfi, Kenza

    2011-01-01

    Corrigiola telephiifolia Pourr. (Caryophyllaceae) is a Moroccan medicinal plant. Despite its popular usage, no study has been published concerning its toxicological profile. The acute toxicity of C. telephiifolia root extract was evaluated by giving it orally to mice at single doses of 5000, 10000, and 14000 mg/kg bodyweight. The extract was also administered at doses of 5, 70, and 2000 mg/kg bodyweight per day to rats for a forty-day toxicity study. No mortality or signs of toxicity were observed in the acute study. In the forty-day study in rats, the extract at 5 mg/kg/day showed no toxicological effects in either sex. At 70 mg/kg/day, the treated group differed from the control only by a significant decrease in serum concentrations of sodium and chloride ions (P < .05). At the dose of 2000 mg/kg/day, the extract significantly increased the serum concentrations of creatinine, alkaline phosphatase, gamma-glutamyltransferase and phosphorus (P < .05) all suggestive of functional nephrotoxicity and hepatotoxicity. The relative bodyweight of both sexes decreased at the dose of 2000 mg/kg/day, with a fast recovery for males. Histological examination did not reveal any treatment-related effects. In conclusion, Corrigiola extract appears safe at the doses used ethno-medicinally. Much higher doses pose toxicological risks. PMID:20953424

  15. Toxicity profile of choline chloride-based deep eutectic solvents for fungi and Cyprinus carpio fish.

    PubMed

    Juneidi, Ibrahim; Hayyan, Maan; Mohd Ali, Ozair

    2016-04-01

    An investigation on the toxicological assessment of 10 choline chloride (ChCl)-based deep eutectic solvents (DESs) towards four fungi strains and Cyprinus carpio fish was conducted. ChCl was combined with materials from different chemical groups such as alcohols, sugars, acids and others to form DESs. The study was carried out on the individual DES components, their aqueous mixture before DES formation and their formed DESs. The agar disc diffusion method was followed to investigate their toxicity on four fungi strains selected as a model of eukaryotic microorganisms (Phanerochaete chrysosporium, Aspergillus niger, Lentinus tigrinus and Candida cylindracea). Among these DESs, ChCl:ZnCl2 exhibited the highest inhibition zone diameter towards the tested fungi growth in vitro, followed by the acidic group (malonic acid and p-toluenesulfonic acid). Another study was conducted to test the acute toxicity and determine the lethal concentration at 50 % (LC50) of the same DESs on C. carpio fish. The inhibition range and LC50 of DESs were found to be different from their individual components. DESs were found to be less toxic than their mixture or individual components. The LC50 of ChCl:MADES is much higher than that of ChCl:MAMix. Moreover, the DESs acidic group showed a lower inhibition zone on fungi growth. Thus, DESs should be considered as new components with different physicochemical properties and toxicological profiles, and not merely compositions of compounds. PMID:26743645

  16. The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a "Central Dogma" for Toxic Mechanisms?

    PubMed

    Park, Yeong-Chul; Lee, Sundong; Cho, Myung-Haing

    2014-09-01

    Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems. PMID:25343011

  17. The added value of the 90-day repeated dose oral toxicity test for industrial chemicals with a low (sub)acute toxicity profile in a high quality dataset.

    PubMed

    Taylor, Katy; Andrew, David J; Rego, Laura

    2014-08-01

    A survey conducted on the EU Notification of New Substances (NONS) database suggested that for industrial chemicals with a profile of low toxicity in (sub)acute toxicity tests there is little added value to the conduct of the 90-day repeated dose study. Avoiding unnecessary animal testing is a central aim of the EU REACH chemicals legislation; therefore we sought to verify the profile using additional data. The OECD's eChemPortal was searched for substances that had both a 28-day and a 90-day study and their robust study summaries were then examined from the ECHA CHEM database. Out of 182 substances with high quality 28-day and 90-day study results, only 18 reported no toxicity of any kind in the (sub)acute tests. However, for 16 of these there were also no reported signs of toxicity at or close to the limit dose (1000mg/kgbw/d) in the 90-day study. Restricting the 'low (sub)acute toxicity in a high quality dataset' profile to general industrial chemicals of no known biological activity, whilst allowing irritant substances, increases the data set and improves the prediction to 95% (20 substances out of 21 substances). The low toxicity profile appears to be of low prevalence within industrial chemicals (10-15%), nevertheless, avoidance of the conduct of a redundant 90-day study for this proportion of the remaining REACH phase-in substances would avoid the use of nearly 50,000 animals and save industry 50million Euros, with no impact on the assessment of human health. PMID:24768988

  18. 3D printed polymers toxicity profiling: a caution for biodevice applications

    NASA Astrophysics Data System (ADS)

    Zhu, Feng; Skommer, Joanna; Friedrich, Timo; Kaslin, Jan; Wlodkowic, Donald

    2015-12-01

    A recent revolution in additive manufacturing technologies and access to 3D Computer Assisted Design (CAD) software has spurred an explosive growth of new technologies in biomedical engineering. This includes biomodels for diagnosis, surgical training, hard and soft tissue replacement, biodevices and tissue engineering. Moreover, recent developments in high-definition additive manufacturing systems such as Multi-Jet Modelling (MJM) and Stereolithography (SLA), capable of reproducing feature sizes close to 100 μm, promise brand new capabilities in fabrication of optical-grade biomicrofluidic Lab-on-a-Chip and MEMS devices. Compared with other rapid prototyping technologies such as soft lithography and infrared laser micromachining in PMMA, SLA and MJM systems can enable user-friendly production of prototypes, superior feature reproduction quality and comparable levels of optical transparency. Prospectively they can revolutionize fabrication of microfluidic devices with complex geometric features and eliminate the need to use clean room environment and conventional microfabrication techniques. In this work we demonstrate preliminary data on toxicity profiling of a panel of common polymers used in 3D printing applications. The main motivation of our work was to evaluate toxicity profiles of most commonly used polymers using standardized biotests according to OECD guidelines for testing of chemic risk assessment. Our work for the first time provides a multispecies view of potential dangers and limitation for building biocompatible devices using FDM, SLA and MJM additive manufacturing systems. Our work shows that additive manufacturing holds significant promise for fabricating LOC and MEMS but requires caution when selecting systems and polymers due to toxicity exhibited by some 3D printing polymers.

  19. Results of the Updated NASA Kennedy Space Center 50-MHz Doppler Radar Wind Profiler Operational Acceptance Test

    NASA Technical Reports Server (NTRS)

    Barbre', Robert E., Jr.; Deker, Ryan K.; Leahy, Frank B.; Huddleston, Lisa

    2016-01-01

    We present here the methodology and results of the Operational Acceptance Test (OAT) performed on the new Kennedy Space Center (KSC) 50-MHz Doppler Radar Wind Profiler (DRWP). On day-of-launch (DOL), space launch vehicle operators have used data from the DRWP to invalidate winds in prelaunch loads and trajectory assessments due to the DRWP's capability to quickly identify changes in the wind profile within a rapidly-changing wind environment. The previous DRWP has been replaced with a completely new system, which needs to undergo certification testing before being accepted for use in range operations. The new DRWP replaces the previous three-beam system made of coaxial cables and a copper wire ground plane with a four-beam system that uses Yagi antennae with enhanced beam steering capability. In addition, the new system contains updated user interface software while maintaining the same general capability as the previous system. The new DRWP continues to use the Median Filter First Guess (MFFG) algorithm to generate a wind profile from Doppler spectra at each range gate. DeTect (2015) contains further details on the upgrade. The OAT is a short-term test designed so that end users can utilize the new DRWP in a similar manner to the previous DRWP during mission operations at the Eastern Range in the midst of a long-term certification process. This paper describes the Marshall Space Flight Center Natural Environments Branch's (MSFC NE's) analyses to verify the quality and accuracy of the DRWP's meteorological data output as compared to the previous DRWP. Ultimately, each launch vehicle program has the responsibility to certify the system for their own use.

  20. Classification and toxicity mechanisms of novel flame retardants (NFRs) based on whole genome expression profiling.

    PubMed

    Guan, Miao; Su, Guanyong; Giesy, John P; Zhang, Xiaowei

    2016-02-01

    Recently some novel alternative flame retardants (NFRs), which have been widely applied to meet demands for mandated flame retardation of products, have been detected in various matrices of the environment. However, knowledge on toxic effects and associated molecular mechanisms of these chemicals was limited. Here, toxic mechanisms of action of six NFRs, bis (2-ethylhexyl) phosphate (BEHP), chlorendic acid (Het acid), 2,2-bis (bromomethyl)-1,3-propanediol (BMP), tris (2-butoxyethyl) phosphate (TBEP), triethyl phosphate (TEP), tributyl phosphate (TBP) were investigated by use of a library containing ∼1820 modified green fluorescent protein (GFP) expressing promoter reporter vectors constructed from Escherichia coli K12(E.coli). BEHP, Het acid, BMP, TBEP, TEP, TBP inhibited growth of E. coli with 4 h 10%-inhibition concentrations of 53.0-3102.3 μM. A total of 119, 44, 26, 131, 62, 103 genes out of 336 genes selected during preliminary screening were significantly altered with fold-changes greater than 1.5 by BEHP, Het acid, BMP, TBEP, TEP and TBP, respectively. GO analyses of responsive genes suggested that RNA and primary metabolism process were involved in molecular mechanisms of toxicity. Chemical clustering based on expression of 62 multi-responsive genes showed that BEHP, TBP and TBEP were grouped together, which is consistent with similarity of their chemical structures, especially for BEHP and TBP. Clustering by molecular descriptors and molecular activity by use of the multivariate classification system ToxCast was consistent with that by profiles of multi-responsive genes. The results of this study demonstrated the utility of the E. coli, whole-cell assay for determining mechanisms of toxic action of chemicals. PMID:26588597

  1. Assessing mechanisms of toxicant response in the amphipod Melita plumulosa through transcriptomic profiling.

    PubMed

    Hook, Sharon E; Osborn, Hannah L; Spadaro, David A; Simpson, Stuart L

    2014-01-01

    This study describes the function of transcripts with altered abundance in the epibenthic amphipod, Melita plumulosa, following whole-sediment exposure to a series of common environmental contaminants. M. plumulosa were exposed for 48 h to sediments spiked and equilibrated with the following contaminants at concentrations predicted to cause sublethal effects to reproduction: porewater ammonia 30 mg L(-1); bifenthrin at 100 μg kg(-1); fipronil at 50 μg kg(-1); 0.6% diesel; 0.3% crude oil; 250 mg Cu kg(-1); 400 mg Ni kg(-1); and 400 mg Zn kg(-1). RNA was extracted and hybridized against a custom Agilent microarray developed for this species. Although the microarray represented a partial transcriptome and not all features on the array could be annotated, unique transcriptomic profiles were generated for each of the contaminant exposures. Hierarchical clustering grouped the expression profiles together by contaminant class, with copper and zinc, the petroleum products and nickel, and the pesticides each forming a distinct cluster. Many of the transcriptional changes observed were consistent with patterns previously described in other crustaceans. The changes in the transcriptome demonstrated that contaminant exposure caused changes in digestive function, growth and moulting, and the cytoskeleton following metal exposure, whereas exposure to petroleum products caused changes in carbohydrate metabolism, xenobiotic metabolism and hormone cycling. Functional analysis of these gene expression profiles can provide a better understanding of modes of toxic action and permits the prediction of mixture effects within contaminated ecosystems. PMID:24334007

  2. Profiling Developmental Toxicity of 387 Environmental Chemicals using EPA’s Toxicity Reference Database (ToxRefDB)

    EPA Science Inventory

    EPA's Toxicity Reference Databases (ToxRefDB) was developed by the National Center for Computational Toxicology in partnership with EPA's Office of Pesticide Programs, to store data derived from in vivo animal toxicity studies [www.epa.gov/ncct/toxrefdb/]. The initial build of To...

  3. Consumer acceptability and sensory profile of cooked broccoli with mustard seeds added to improve chemoprotective properties.

    PubMed

    Ghawi, Sameer Khalil; Shen, Yuchi; Niranjan, Keshavan; Methven, Lisa

    2014-09-01

    Broccoli, a rich source of glucosinolates, is a commonly consumed vegetable of the Brassica family. Hydrolysis products of glucosinolates, isothiocyanates, have been associated with health benefits and contribute to the flavor of Brassica. However, boiling broccoli causes the myrosinase enzyme needed for hydrolysis to denature. In order to ensure hydrolysis, broccoli must either be mildly cooked or active sources of myrosinase, such as mustard seed powder, can be added postcooking. In this study, samples of broccoli were prepared in 6 different ways; standard boiling, standard boiling followed by the addition of mustard seeds, sous vide cooking at low temperature (70 °C) and sous vide cooking at higher temperature (100 °C) and sous vide cooking at higher temperature followed by the addition of mustard seeds at 2 different concentrations. The majority of consumers disliked the mildly cooked broccoli samples (70 °C, 12 min, sous vide) which had a hard and stringy texture. The highest mean consumer liking was for standard boiled samples (100 °C, 7 min). Addition of 1% mustard seed powder developed sensory attributes, such as pungency, burning sensation, mustard odor, and flavor. One cluster of consumers (32%) found mustard seeds to be a good complement to cooked broccoli; however, the majority disliked the mustard-derived sensory attributes. Where the mustard seeds were partially processed, doubling the addition to 2% led to only the same level of mustard and pungent flavors as 1% unprocessed seeds, and mean consumer liking remained unaltered. This suggests that optimization of the addition level of partially processed mustard seeds may be a route to enhance bioactivity of cooked broccoli without compromising consumer acceptability. PMID:25156799

  4. Gene expression profiling in liver and testis of rats to characterize the toxicity of triazole fungicides

    SciTech Connect

    Tully, Douglas B.; Bao Wenjun; Goetz, Amber K.; Blystone, Chad R.; Ren, Hongzu; Schmid, Judith E.; Strader, Lillian F.; Wood, Carmen R.; Best, Deborah S.; Narotsky, Michael G.; Wolf, Douglas C.; Rockett, John C.; Dix, David J. . E-mail: dix.david@epa.gov

    2006-09-15

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected for hormone measurements, and liver and testes were collected for histology, enzyme biochemistry, or gene expression profiling. Body and testis weights were unaffected, but liver weights were significantly increased by all four triazoles, and hepatocytes exhibited centrilobular hypertrophy. Myclobutanil exposure increased serum testosterone and decreased sperm motility, but no treatment-related testis histopathology was observed. We hypothesized that gene expression profiles would identify potential mechanisms of toxicity and used DNA microarrays and quantitative real-time PCR (qPCR) to generate profiles. Triazole fungicides are designed to inhibit fungal cytochrome P450 (CYP) 51 enzyme but can also modulate the expression and function of mammalian CYP genes and enzymes. Triazoles affected the expression of numerous CYP genes in rat liver and testis, including multiple Cyp2c and Cyp3a isoforms as well as other xenobiotic metabolizing enzyme (XME) and transporter genes. For some genes, such as Ces2 and Udpgtr2, all four triazoles had similar effects on expression, suggesting possible common mechanisms of action. Many of these CYP, XME and transporter genes are regulated by xeno-sensing nuclear receptors, and hierarchical clustering of CAR/PXR-regulated genes demonstrated the similarities of toxicogenomic responses in liver between all four triazoles and in testis between myclobutanil and triadimefon. Triazoles also affected expression of multiple genes involved in steroid hormone metabolism in the two tissues. Thus, gene expression profiles helped identify possible toxicological mechanisms of the triazole fungicides.

  5. Toxicity profile of lisdexamfetamine dimesylate in three independent rat toxicology studies.

    PubMed

    Krishnan, Suma; Montcrief, Scott

    2007-10-01

    Lisdexamfetamine dimesylate (LDX) is a d-amphetamine prodrug developed for the treatment of attention-deficit/hyperactivity disorder. The toxicity profile of orally administered LDX has been evaluated in rats. In an acute study, LDX doses of 60 mg/kg and higher caused increased motor activity. At 1000 mg/kg, one rat died and another was euthanized. In a 7-day repeat-dose study, all rats dosed with LDX (14 per dose group for each sex) showed increased activity; 10 male rats and 11 female rats at 300 mg/kg/day and 3 female rats at 100 mg/kg/day were euthanized because of self-mutilation and 1 male rat at 300 mg/kg/day was found dead. In a 28-day study, only rats at 80 mg/kg showed signs of self-mutilation and thin body condition. In both the 7- and 28-day studies, LDX caused significant changes in some blood chemistry parameters (e.g. blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase) and organ weights (e.g. particularly heart, liver, brain, and spleen). Overall, no apparent treatment-related histopathologic changes were observed. Toxicokinetic assessments indicated that as the dose of LDX was increased, rats were exposed to increasing levels of LDX and d-amphetamine. The extent of exposure to LDX and d-amphetamine increased after repeated-dose in the 28-day study. The findings of the repeat-dose studies indicate that the toxicity profile in rats administered LDX orally is comparable to that for d-amphetamine; however, the apparent lethal dose of LDX in rats is more than five times higher than the LD(50) of orally administered d-amphetamine, supporting a putative protective effect of conjugating amphetamine with lysine. PMID:17845504

  6. Effects of Dietary Selenium Against Lead Toxicity Are Related to the Ion Profile in Chicken Muscle.

    PubMed

    Jin, Xi; Liu, Chun Peng; Teng, Xiao Hua; Fu, Jing

    2016-08-01

    Complex antagonistic interactions between Selenium (Se) and heavy metals have been reported in previous studies. However, little is known regarding the effects of Se on lead (Pb)-induced toxicity and the ion profile in the muscles of chickens. In this present study, we fed chickens either Se or Pb or both Se and Pb supplement and later analyzed the concentrations of 26 ions in chicken muscle tissues. We determined that a Se- and Pb-containing diets significantly affected microelements in chicken muscle. Treatment with Se increased the content of Se but resulted in a reduced concentration of Cu, As, Cd, Sn, Hg, and Ba. Treatment with Pb increased concentrations of Ni while reducing those of B, V, Cr, Fe, Co, Cu, Zn, and Mo. Moreover, Se also reduced the concentration of Pb, Zn, Co, Fe, V, and Cr, which in contrast were induced by Pb. Additionally, we also found that synergistic and antagonistic interactions existed between Se and Pb supplementation. Our findings suggested that Se can exert a negative effect on Pb in chicken muscle tissues and may be related to changes in ion profiles. PMID:26743866

  7. GENE EXPRESSION PROFILING OF ACCESSIBLE SURROGATE TISSUES TO MONITOR MOLECULAR CHANGES IN INACCESSIBLE TARGET TISSUES FOLLOWING TOXICANT EXPOSURE

    EPA Science Inventory

    Gene Expression Profiling Of Accessible Surrogate Tissues To Monitor Molecular Changes In Inaccessible Target Tissues Following Toxicant Exposure
    John C. Rockett, Chad R. Blystone, Amber K. Goetz, Rachel N. Murrell, Judith E. Schmid and David J. Dix
    Reproductive Toxicology ...

  8. The relationship between developmental toxicity and aromatic-ring class profile of high-boiling petroleum substances.

    PubMed

    Murray, F Jay; Roth, Randy N; Nicolich, Mark J; Gray, Thomas M; Simpson, Barry J

    2013-11-01

    In response to the US EPA HPV Challenge Program, this study was conducted to: (1) evaluate the relationship between PAC content and the developmental toxicity of high-boiling petroleum substances (HBPS) and (2) develop mathematical models to predict the developmental toxicity of similar untested substances based on their aromatic ring class (ARC) profiles. For this investigation, 68 developmental toxicity studies were reviewed. The ARC models relied on data from 21 rat dermal developmental toxicity studies conducted with similar experimental designs to ensure a consistent data set for comparison. The most sensitive general endpoints of developmental toxicity (i.e., decreased fetal survival and growth) were chosen for modeling. The ARC models demonstrated a strong correlation between the predicted vs. observed values for specific sensitive endpoints of these developmental toxicities (percent resorptions, r=0.99; live fetuses per litter, r=0.98; fetal body weight, r=0.94). Such associations provide a promising approach for predicting the developmental toxicity of untested HBPS. Efforts to corroborate the ARC models using test substances that were not used to build the ARC models produced mixed results, and further development and refinement of the ARC models is recommended before they can be reliably applied to all HBPS. PMID:23680405

  9. Toxicity of coarse and fine particulate matter from sites with contrasting traffic profiles.

    PubMed

    Gerlofs-Nijland, Miriam E; Dormans, Jan A M A; Bloemen, Henk J T; Leseman, Daan L A C; John, A; Boere, F; Kelly, Frank J; Mudway, Ian S; Jimenez, Al A; Donaldson, Ken; Guastadisegni, Cecilia; Janssen, Nicole A H; Brunekreef, Bert; Sandström, Thomas; van Bree, Leendert; Cassee, Flemming R

    2007-10-01

    Residence in urban areas with much traffic has been associated with various negative health effects. However, the contribution of traffic emissions to these adverse health effects has not been fully determined. Therefore, the objective of this in vivo study is to compare the pulmonary and systemic responses of rats exposed to particulate matter (PM) obtained from various locations with contrasting traffic profiles. Samples of coarse (2.5 microm-10 microm) and fine (0.1 microm-2.5 microm) PM were simultaneously collected at nine sites across Europe with a high-volume cascade impactor. Six PM samples from various locations were selected on the basis of contrast in in vitro analysis, chemical composition, and traffic profiles. We exposed spontaneously hypertensive (SH) rats to a single dose (3 mg PM/kg body weight or 10 mg PM/kg body weight) of either coarse or fine PM by intratracheal instillation. We assessed changes in biochemical markers, cell differentials, and histopathological changes in the lungs and blood 24 h postexposure. The dose-related adverse effects that both coarse and fine PM induced in the lungs and vascular system were mainly related to cytotoxicity, inflammation, and blood viscosity. We observed clear differences in the extent of these responses to PM from the various locations at equivalent dose levels. There was a trend that suggests that samples from high-traffic sites were the most toxic. It is likely that the toxicological responses of SH rats were associated with specific PM components derived from brake wear (copper and barium), tire wear (zinc), and wood smoke (potassium). PMID:17957546

  10. Longitudinal Stability of Social Competence Indicators in a Portuguese Sample: Q-Sort Profiles of Social Competence, Measures of Social Engagement, and Peer Sociometric Acceptance

    ERIC Educational Resources Information Center

    Santos, António J.; Vaughn, Brian E.; Peceguina, Inês; Daniel, João R.

    2014-01-01

    This study examines the temporal stability (over 3 years) of individual differences in 3 domains relevant to preschool children's social competence: social engagement/motivation, profiles of behavior and personality attributes characteristic of socially competent young children, and peer acceptance. Each domain was measured with multiple…

  11. Aerial Prefeeding Followed by Ground Based Toxic Baiting for More Efficient and Acceptable Poisoning of Invasive Small Mammalian Pests

    PubMed Central

    Morgan, David; Warburton, Bruce; Nugent, Graham

    2015-01-01

    Introduced brushtail possums (Trichosurus vulpecula) and rat species (Rattus spp.) are major vertebrate pests in New Zealand, with impacts on conservation and agriculture being managed largely through poisoning operations. Aerial distribution of baits containing sodium fluoroacetate (1080) has been refined to maximise cost effectiveness and minimise environmental impact, but this method is strongly opposed by some as it is perceived as being indiscriminate. Although ground based control enables precise placement of baits, operations are often more than twice as costly as aerial control, mainly due to the high labour costs. We investigated a new approach to ground based control that combined aerial distribution of non-toxic ‘prefeed’ baits followed by sparse distribution of toxic baits at regular intervals along the GPS tracked prefeeding flight paths. This approach was tested in two field trials in which both 1080 baits and cholecalciferol baits were used in separate areas. Effectiveness of the approach, assessed primarily using ‘chewcards’, was compared with that of scheduled aerial 1080 operations that were conducted in outlying areas of both trials. Contractors carrying out ground based control were able to follow the GPS tracks of aerial prefeeding flight lines very accurately, and with 1080 baits achieved very high levels of kill of possums and rats similar to those achieved by aerial 1080 baiting. Cholecalciferol was less effective in the first trial, but by doubling the amount of cholecalciferol bait used in the second trial, few possums or rats survived. By measuring the time taken to complete ground baiting from GPS tracks, we predicted that the method (using 1080 baits) would be similarly cost effective to aerial 1080 operations for controlling possums and rats, and considerably less expensive than typical current costs of ground based control. The main limitations to the use of the method will be access to, and size of, the operational site

  12. Aerial Prefeeding Followed by Ground Based Toxic Baiting for More Efficient and Acceptable Poisoning of Invasive Small Mammalian Pests.

    PubMed

    Morgan, David; Warburton, Bruce; Nugent, Graham

    2015-01-01

    Introduced brushtail possums (Trichosurus vulpecula) and rat species (Rattus spp.) are major vertebrate pests in New Zealand, with impacts on conservation and agriculture being managed largely through poisoning operations. Aerial distribution of baits containing sodium fluoroacetate (1080) has been refined to maximise cost effectiveness and minimise environmental impact, but this method is strongly opposed by some as it is perceived as being indiscriminate. Although ground based control enables precise placement of baits, operations are often more than twice as costly as aerial control, mainly due to the high labour costs. We investigated a new approach to ground based control that combined aerial distribution of non-toxic 'prefeed' baits followed by sparse distribution of toxic baits at regular intervals along the GPS tracked prefeeding flight paths. This approach was tested in two field trials in which both 1080 baits and cholecalciferol baits were used in separate areas. Effectiveness of the approach, assessed primarily using 'chewcards', was compared with that of scheduled aerial 1080 operations that were conducted in outlying areas of both trials. Contractors carrying out ground based control were able to follow the GPS tracks of aerial prefeeding flight lines very accurately, and with 1080 baits achieved very high levels of kill of possums and rats similar to those achieved by aerial 1080 baiting. Cholecalciferol was less effective in the first trial, but by doubling the amount of cholecalciferol bait used in the second trial, few possums or rats survived. By measuring the time taken to complete ground baiting from GPS tracks, we predicted that the method (using 1080 baits) would be similarly cost effective to aerial 1080 operations for controlling possums and rats, and considerably less expensive than typical current costs of ground based control. The main limitations to the use of the method will be access to, and size of, the operational site, along with

  13. The Antagonistic Effect of Selenium on Lead Toxicity Is Related to the Ion Profile in Chicken Liver.

    PubMed

    Xu, Tong; Gao, Xuejiao; Liu, Guowen

    2016-02-01

    The interactions between the essential element selenium (Se) and the toxic element lead (Pb) have been reported extensively; however, limited data are available regarding the effects of Se on Pb and the ion profile in chicken liver. Whether the change in the ion profile was involved in the protective process of Se and the toxic effect of Pb is unknown. In the present study, we detected 26 ion profiles (including those of Na, Mg, K, Ca, B, Si, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Se, Mo, Sb, Ba, Tl, Li, Al, As, Cd, Sn, Hg, and Pb) in chicken liver following treatment with Se or Pb and with the compound treatment of Se and Pb. The results showed that Se supplementation decreased the content of B and Cr and increased that of Zn and Ba (P < 0.05); however, Pb exposure decreased Cr, Mn, Cu, Se, Mo, and Hg and increased V, Fe, Cd, and Sn (P < 0.05). The results showed that Se and Pb primarily influenced essential microelements and toxic microelements in the chicken liver. In this process, Se alleviated the increased Cd and Pb induced by Pb exposure but aggravated the decreased Cu and Mn. The results also indicated that there existed both synergistic and antagonistic interactions between different ions, further verifying the principal component analysis. Thus, the results showed that prolonged exposure to Se and Pb influences the ion profiles in chicken liver. The protective role of Se and toxic effect of Pb may be related to these changing ion profiles in chicken liver. PMID:26123166

  14. Predicting chronic copper and nickel reproductive toxicity to Daphnia pulex-pulicaria from whole-animal metabolic profiles.

    PubMed

    Taylor, Nadine S; Kirwan, Jennifer A; Johnson, Craig; Yan, Norman D; Viant, Mark R; Gunn, John M; McGeer, James C

    2016-05-01

    The emergence of omics approaches in environmental research has enhanced our understanding of the mechanisms underlying toxicity; however, extrapolation from molecular effects to whole-organism and population level outcomes remains a considerable challenge. Using environmentally relevant, sublethal, concentrations of two metals (Cu and Ni), both singly and in binary mixtures, we integrated data from traditional chronic, partial life-cycle toxicity testing and metabolomics to generate a statistical model that was predictive of reproductive impairment in a Daphnia pulex-pulicaria hybrid that was isolated from an historically metal-stressed lake. Furthermore, we determined that the metabolic profiles of organisms exposed in a separate acute assay were also predictive of impaired reproduction following metal exposure. Thus we were able to directly associate molecular profiles to a key population response - reproduction, a key step towards improving environmental risk assessment and management. PMID:26854702

  15. Genomewide Expression Profiling of Cryptolepine-Induced Toxicity in Saccharomyces cerevisiae▿

    PubMed Central

    Rojas, Marta; Wright, Colin W.; Piña, Benjamin; Portugal, José

    2008-01-01

    We have used the budding yeast Saccharomyces cerevisiae to identify genes that may confer sensitivity in vivo to the antimalarial and cytotoxic agent cryptolepine. Five S. cerevisiae strains, with different genetic backgrounds in cell permeability and DNA damage repair mechanisms, were exposed to several concentrations of cryptolepine. Cryptolepine showed a relatively mild toxicity for wild-type strains, which was augmented by either increasing cell permeability (Δerg6 or ISE2 strains) or disrupting DNA damage repair (Δrad52 strains). These results are compatible with the ability of cryptolepine to intercalate into DNA and thus promote DNA lesions. The effects of low concentrations of cryptolepine (20% and 40% inhibitory concentrations [IC20 and IC40]) were analyzed by comparing the gene expression profiles of treated and untreated Δerg6 yeast cells. Significant changes in expression levels were observed for 349 genes (117 upregulated and 232 downregulated). General stress-related genes constituted the only recognizable functional cluster whose expression was increased upon cryptolepine treatment, making up about 20% of upregulated genes. In contrast, analysis of the characteristics of downregulated genes revealed a specific effect of cryptolepine on genes related to iron transport or acid phosphatases, as well as a significant proportion of genes related to cell wall components. The effects of cryptolepine on the transcription of iron transport-related genes were consistent with a loss of function of the iron sensor Aft1p, indicating a possible disruption of iron metabolism in S. cerevisiae. Since the interference of cryptolepine with iron metabolism is considered one of its putative antimalarial targets, this finding supports the utility of S. cerevisiae in drug-developing schemes. PMID:18710911

  16. Toxicity and composition profiles of solid phase extracts of oil sands process-affected water.

    PubMed

    Yue, Siqing; Ramsay, Bruce A; Wang, Jiaxi; Ramsay, Juliana

    2015-12-15

    After fractionation using sequential solid phase extraction, the presence of toxic components in oil sands process-affected water (OSPW) was detected by the Microtox® acute toxicity assay using effect-directed analysis. The composition of each fraction was determined by high-resolution electrospray ionization-Orbitrap mass spectrometry. Partial least-squares discriminant analysis (PLS-DA) was used to determine which chemical constituents in all seven fractions co-varied most strongly with toxicity. Although O2 compounds with double bond equivalence (DBE) between 3 and 9 positively correlated with toxicity, C15-C18 O2-NAs with DBE=4 (tricyclic structure), as well as C14-C17 O2-NAs with DBE=3 (bicyclic structure), were found to be most likely associated with OSPW toxicity, consistent with published toxicity studies of surrogate NAs. O4, many O3 (i.e. possibly hydroxylated O2 c-NAs) and a few O2 compounds were found to negatively correlate with toxicity. The results demonstrate the utility of the fractionation and the PLS-DA approach for evaluating composition-response relationships in a complex mixture and also contribute to a better understanding of the toxic compounds in OSPW. These findings will help to focus study on the most environmentally significant components in OSPW. PMID:26318810

  17. Strategies for integrating transcriptional profiling into high throughput toxicity testing (SOT Symposium Workshop presentation)

    EPA Science Inventory

    Presentation Description: The release of the National Research Council’s Report “Toxicity Testing in the 21st Century: A Vision and a Strategy” in 2007 initiated a broad-based movement in the toxicology community to re-think how toxicity testing and risk assessment are performed....

  18. Constitutive gene expression profile segregates toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy

    PubMed Central

    Henríquez Hernández, Luis Alberto; Lara, Pedro Carlos; Pinar, Beatriz; Bordón, Elisa; Gallego, Carlos Rodríguez; Bilbao, Cristina; Pérez, Leandro Fernández; Morales, Amílcar Flores

    2009-01-01

    Breast cancer patients show a wide variation in normal tissue reactions after radiotherapy. The individual sensitivity to x-rays limits the efficiency of the therapy. Prediction of individual sensitivity to radiotherapy could help to select the radiation protocol and to improve treatment results. The aim of this study was to assess the relationship between gene expression profiles of ex vivo un-irradiated and irradiated lymphocytes and the development of toxicity due to high-dose hyperfractionated radiotherapy in patients with locally advanced breast cancer. Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database (GEO accession GSE15341). We obtained a small group of 81 genes significantly regulated by radiotherapy, lumped in 50 relevant pathways. Using ANOVA and t-test statistical tools we found 20 and 26 constitutive genes (0 Gy) that segregate patients with and without acute and late toxicity, respectively. Non-supervised hierarchical clustering was used for the visualization of results. Six and 9 pathways were significantly regulated respectively. Concerning to irradiated lymphocytes (2 Gy), we founded 29 genes that separate patients with acute toxicity and without it. Those genes were gathered in 4 significant pathways. We could not identify a set of genes that segregates patients with and without late toxicity. In conclusion, we have found an association between the constitutive gene expression profile of peripheral blood lymphocytes and the development of acute and late toxicity in consecutive, unselected patients. These observations suggest the possibility of predicting normal tissue response to irradiation in high-dose non-conventional radiation therapy regimens. Prospective studies with higher number of patients are needed to validate these preliminary results. PMID:19497124

  19. Gene Expression Profile and Toxic Effects in Human Bronchial Epithelial Cells Exposed to Zearalenone

    PubMed Central

    So, Mei Yu; Tian, ZhiPeng; Phoon, Yong Shian; Sha, Sha; Antoniou, Michael N.; Zhang, JiangWen; Wu, Rudolf S. S.; Tan-Un, Kian C

    2014-01-01

    Zearalenone (ZEA), a mycoestrogen produced by Fusarium fungal species, is mainly found in cereal crops such as maize, wheat and barley. Although ZEA has been reported to be present in air, little is known about the health risk or the molecular basis of action when lung cells are exposed to ZEA. As ZEA has a similar structure to estrogen, its potential risk as an endocrine disrupting chemical (EDC) has thus aroused both environmental and public health concerns. The purpose of this study is to identify the responses and underlying molecular changes that occur when human bronchial epithelial BEAS-2B cells are exposed to ZEA. Differential gene expression profiles were identified in cells that were treated with 40 µM ZEA for 6 h and 24 h by high-throughput microarray analysis using Affymetrix Human Gene 2.0 GeneChip. The array results showed that after ZEA treatment, 262 genes at 6 h and 1073 genes at 24 h were invovled in the differential regulation. Pathway analysis revealed that diverse cellular processes were affected when lung cells were exposed to ZEA resulting in impaired response to DNA damage, cell cycle arrest, down-regulation of inflammatory responses and alterations of epigenetic marks. Results of further experiments indicated that 40 µM ZEA decreased cell viability, induced apoptosis and promoted reactive oxygen species (ROS) generation in a time-dependent manner. Immuno-suppressive effects of ZEA were further revealed through the suppression of lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines (IL-6, IL-8 and IL-1β). Interestingly, the level of global DNA methylation was markedly decreased after 24 h exposure to ZEA. Collectively, these observations suggested that a broad range of toxic effects are elicited by ZEA. Particularly, ROS may play a pivotal role in ZEA-induced cell death. These adverse effects observed in lung cells suggest that exposure to ZEA may increase susceptibility of lung cells to diseases and required further

  20. Toxicity and binding profile of lectins from the Genus canavalia on brine shrimp.

    PubMed

    Arruda, Francisco Vassiliepe Sousa; Melo, Arthur Alves; Vasconcelos, Mayron Alves; Carneiro, Romulo Farias; Barroso-Neto, Ito Liberato; Silva, Suzete Roberta; Pereira-Junior, Francisco Nascimento; Nagano, Celso Shiniti; Nascimento, Kyria Santiago; Teixeira, Edson Holanda; Saker-Sampaio, Silvana; Sousa Cavada, Benildo; Sampaio, Alexandre Holanda

    2013-01-01

    Lectins are sugar-binding proteins widely distributed in nature with many biological functions. Although many lectins have a remarkable biotechnological potential, some of them can be cytotoxic. Thus, the aim of this study was to assess the toxicity of five lectins, purified from seeds of different species of Canavalia genus. In order to determine the toxicity, assays with Artemia nauplii were performed. In addition, a fluorescence assay was carried out to evaluate the binding of lectins to Artemia nauplii. In order to verify the relationship between the structure of lectins and their cytotoxic effect, structural analysis was carried out to evaluate the volume of the carbohydrate recognition domain (CRD) of each lectin. The results showed that all lectins exhibited different toxicities and bound to a similar area in the digestive tract of Artemia nauplii. Concerning the structural analysis, differences in spatial arrangement and volume of CRD may explain the variation of the toxicity exhibited by each lectin. To this date, this is the first study that establishes a link between toxicity and structure of CRD from Diocleinae lectins. PMID:24380079

  1. Insights on cryoprotectant toxicity from gene expression profiling of endothelial cells exposed to ethylene glycol.

    PubMed

    Cordeiro, Rui Martins; Stirling, Soren; Fahy, Gregory M; de Magalhães, João Pedro

    2015-12-01

    Cryopreservation consists of preserving living cells or tissues generally at -80 °C or below and has many current applications in cell and tissue banking, and future potential for organ banking. Cryoprotective agents such as ethylene glycol (EG) are required for successful cryopreservation of most living systems, but have toxic side effects whose mechanisms remain largely unknown. In this work, we investigated the mechanisms of toxicity of ethylene glycol in human umbilical vein endothelial cells (HUVECs) as a model of the vascular endothelium in perfused organs. Exposing cells to 60% v/v EG for 2 h at 4 °C resulted in only a slight decrease in subsequent cell growth, suggesting only modest toxicity of EG for this cell type. Gene expression analysis with whole genome microarrays revealed signatures indicative of a generalized stress response at 24 h after EG exposure and a trend toward partial recovery at 72 h. The observed changes involved signalling pathways, glycoproteins, and genes involved in extracellular and transmembrane functions, the latter suggesting potential effects of ethylene glycol on membranes. These results continue to develop a new paradigm for understanding cryoprotectant toxicity and reveal molecular signatures helpful for future experiments in more completely elucidating the toxic effects of ethylene glycol in vascular endothelial cells and other cell types. PMID:26471925

  2. Toxicity and Binding Profile of Lectins from the Genus Canavalia on Brine Shrimp

    PubMed Central

    Arruda, Francisco Vassiliepe Sousa; Melo, Arthur Alves; Vasconcelos, Mayron Alves; Carneiro, Romulo Farias; Barroso-Neto, Ito Liberato; Silva, Suzete Roberta; Pereira-Junior, Francisco Nascimento; Nagano, Celso Shiniti; Nascimento, Kyria Santiago; Teixeira, Edson Holanda; Saker-Sampaio, Silvana; Sousa Cavada, Benildo; Sampaio, Alexandre Holanda

    2013-01-01

    Lectins are sugar-binding proteins widely distributed in nature with many biological functions. Although many lectins have a remarkable biotechnological potential, some of them can be cytotoxic. Thus, the aim of this study was to assess the toxicity of five lectins, purified from seeds of different species of Canavalia genus. In order to determine the toxicity, assays with Artemia nauplii were performed. In addition, a fluorescence assay was carried out to evaluate the binding of lectins to Artemia nauplii. In order to verify the relationship between the structure of lectins and their cytotoxic effect, structural analysis was carried out to evaluate the volume of the carbohydrate recognition domain (CRD) of each lectin. The results showed that all lectins exhibited different toxicities and bound to a similar area in the digestive tract of Artemia nauplii. Concerning the structural analysis, differences in spatial arrangement and volume of CRD may explain the variation of the toxicity exhibited by each lectin. To this date, this is the first study that establishes a link between toxicity and structure of CRD from Diocleinae lectins. PMID:24380079

  3. The affective profiles, psychological well-being, and harmony: environmental mastery and self-acceptance predict the sense of a harmonious life

    PubMed Central

    Al Nima, Ali; Kjell, Oscar N.E.

    2014-01-01

    Background. An important outcome from the debate on whether wellness equals happiness, is the need of research focusing on how psychological well-being might influence humans’ ability to adapt to the changing environment and live in harmony. To get a detailed picture of the influence of positive and negative affect, the current study employed the affective profiles model in which individuals are categorised into groups based on either high positive and low negative affect (self-fulfilling); high positive and high negative affect (high affective); low positive and low negative affect (low affective); and high negative and low positive affect (self-destructive). The aims were to (1) investigate differences between affective profiles in psychological well-being and harmony and (2) how psychological well-being and its dimensions relate to harmony within the four affective profiles. Method. 500 participants (mean age = 34.14 years, SD. = ±12.75 years; 187 males and 313 females) were recruited online and required to answer three self-report measures: The Positive Affect and Negative Affect Schedule; The Scales of Psychological Well-Being (short version) and The Harmony in Life Scale. We conducted a Multivariate Analysis of Variance where the affective profiles and gender were the independent factors and psychological well-being composite score, its six dimensions as well as the harmony in life score were the dependent factors. In addition, we conducted four multi-group (i.e., the four affective profiles) moderation analyses with the psychological well-being dimensions as predictors and harmony in life as the dependent variables. Results. Individuals categorised as self-fulfilling, as compared to the other profiles, tended to score higher on the psychological well-being dimensions: positive relations, environmental mastery, self-acceptance, autonomy, personal growth, and purpose in life. In addition, 47% to 66% of the variance of the harmony in life was explained by

  4. Assessing urban stormwater toxicity: methodology evolution from point observations to longitudinal profiling.

    PubMed

    Grapentine, Lee; Rochfort, Quintin; Marsalek, Jiri

    2008-01-01

    The quality of aquatic habitat in a stormwater management facility located in Toronto, Ontario, was assessed by examining ecotoxicological responses of benthic invertebrates exposed to sediment and water from this system. Besides residential stormwater, the facility receives highway runoff contaminated with trace metals, polycyclic aromatic hydrocarbons (PAHs), and road salt. The combined flow passes through two extended detention ponds (in series) and a vegetated outlet channel. Toxicity of surficial sediment collected from 14 longitudinally arrayed locations was assessed based on 10 acute and chronic endpoints from laboratory tests with four benthic organisms. Greatest overall toxicity was observed in sediment from sites in the upstream pond, where mortality to amphipods and mayflies reached up to 100%. Downstream pond sediment was less toxic on average than the upstream pond sediment, but not the outlet channel sediment where untreated stormwater discharges provided additional sources of contamination. Macroinvertebrate communities in sediment cores were depauperate and dominated by oligochaetes and chironomids, with minimum densities and diversity at the deeper central pond sites. While sediment toxicity was associated with high concentrations of trace metals and high-molecular weight PAHs, benthic community impoverishment appeared related to high water column salinity. PMID:18496002

  5. Speciation Profiles and Toxic Emission Factors for Nonroad Engines: DRAFT REPORT

    EPA Science Inventory

    This document details the research and development behind how MOVES2014a estimates air toxic emissions for nonroad engines and equipment run on conventional gasoline without ethanol (E0) and gasoline blended with 10% ethanol (E10) as well as diesel fuel, compressed natural gas (C...

  6. Transcriptional profiling of Al toxicity and tolerance responses in maize roots

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aluminum (Al) toxicity is a major factor limiting crop yields on acid soils. Plant species exhibit considerable genotypic variation for Al tolerance, which is being exploited by researchers to identify the mechanisms that underlie this trait. In maize, Al tolerance is a complex phenomenon involving ...

  7. High Throughput Prioritization for Integrated Toxicity Testing Based on ToxCast Chemical Profiling

    EPA Science Inventory

    The rational prioritization of chemicals for integrated toxicity testing is a central goal of the U.S. EPA’s ToxCast™ program (http://epa.gov/ncct/toxcast/). ToxCast includes a wide-ranging battery of over 500 in vitro high-throughput screening assays which in Phase I was used to...

  8. Using in vitro Dose-Response Profiles to Enhance QSAR Modeling of in vivo Toxicity

    EPA Science Inventory

    To develop effective means for rapid toxicity evaluation of environmental chemicals, the Tox21 partnership among the National Toxicology Program (NTP), NIH Chemical Genomics Center, and National Center for Computational Toxicology (NCCT) at the US EPA are conducting a number of ...

  9. Predictive Signatures of Developmental Toxicity Modeled with HTS Data from ToxCast™ Bioactivity Profiles

    EPA Science Inventory

    The EPA ToxCast™ research program uses a high-throughput screening (HTS) approach for predicting the toxicity of large numbers of chemicals. Phase-I contains 309 well-characterized chemicals which are mostly pesticides tested in over 600 assays of different molecular targets, cel...

  10. 78 FR 17213 - Agency for Toxic Substances and Disease Registry Availability of Final Toxicological Profile

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-20

    ... of the 275 priority substances was announced in the Federal Register on November 3rd, 2011 (76 FR... published in the Federal Register on April 27, 2011 (76 FR 23600), with notice of a 90-day public comment... HUMAN SERVICES Agency for Toxic Substances and Disease Registry Availability of Final...

  11. "Would you accept having your DNA profile inserted in the National Forensic DNA database? Why?" Results of a questionnaire applied in Portugal.

    PubMed

    Machado, Helena; Silva, Susana

    2014-01-01

    The creation and expansion of forensic DNA databases might involve potential threats to the protection of a range of human rights. At the same time, such databases have social benefits. Based on data collected through an online questionnaire applied to 628 individuals in Portugal, this paper aims to analyze the citizens' willingness to donate voluntarily a sample for profiling and inclusion in the National Forensic DNA Database and the views underpinning such a decision. Nearly one-quarter of the respondents would indicate 'no', and this negative response increased significantly with age and education. The overriding willingness to accept the inclusion of the individual genetic profile indicates an acknowledgement of the investigative potential of forensic DNA technologies and a relegation of civil liberties and human rights to the background, owing to the perceived benefits of protecting both society and the individual from crime. This rationale is mostly expressed by the idea that all citizens should contribute to the expansion of the National Forensic DNA Database for reasons that range from the more abstract assumption that donating a sample for profiling would be helpful in fighting crime to the more concrete suggestion that everyone (criminals and non-criminals) should be in the database. The concerns with the risks of accepting the donation of a sample for genetic profiling and inclusion in the National Forensic DNA Database are mostly related to lack of control and insufficient or unclear regulations concerning safeguarding individuals' data and supervising the access and uses of genetic data. By providing an empirically-grounded understanding of the attitudes regarding willingness to donate voluntary a sample for profiling and inclusion in a National Forensic DNA Database, this study also considers the citizens' perceived benefits and risks of operating forensic DNA databases. These collective views might be useful for the formation of international common

  12. Investigating the chemical profile of regenerated scorpion (Parabuthus transvaalicus) venom in relation to metabolic cost and toxicity.

    PubMed

    Nisani, Zia; Boskovic, Danilo S; Dunbar, Stephen G; Kelln, Wayne; Hayes, William K

    2012-09-01

    We investigated the biochemical profile of regenerated venom of the scorpion Parabuthus transvaalicus in relation to its metabolic cost and toxicity. Using a closed-system respirometer, we compared oxygen consumption between milked and unmilked scorpions to determine the metabolic costs associated with the first 192 h of subsequent venom synthesis. Milked scorpions had a substantially (21%) higher mean metabolic rate than unmilked scorpions, with the largest increases in oxygen consumption occurring at approximately 120 h, 162 h, and 186 h post-milking. Lethality tests in crickets indicated that toxicity of the regenerated venom returned to normal levels within 4 d after milking. However, the chemical profile of the regenerated venom, as evaluated by FPLC and MALDI-TOF mass spectrometry, suggested that regeneration of different venom components was asynchronous. Some peptides regenerated quickly, particularly those associated with the scorpion's "prevenom," whereas others required much or all of this time period for regeneration. This asynchrony could explain the different spikes detected in oxygen consumption of milked scorpions as various peptides and other venom components were resynthesized. These observations confirm the relatively high metabolic cost of venom regeneration and suggest that greater venom complexity can be associated with higher costs of venom production. PMID:22564718

  13. Transcriptome assembly and expression profiling of molecular responses to cadmium toxicity in hepatopancreas of the freshwater crab Sinopotamon henanense

    PubMed Central

    Sun, Min; Ting Li, Yi; Liu, Yang; Chin Lee, Shao; Wang, Lan

    2016-01-01

    Cadmium (Cd) pollution is a serious global problem, which causes irreversible toxic effects on animals. Freshwater crab, Sinopotamon henanense, is a useful environmental indicator since it is widely distributed in benthic habitats whereby it tends to accumulate Cd and other toxicants. However, its molecular responses to Cd toxicity remain unclear. In this study, we performed transcriptome sequencing and gene expression analyses of its hepatopancreas with and without Cd treatments. A total of 7.78 G clean reads were obtained from the pooled samples, and 68,648 unigenes with an average size of 622 bp were assembled, in which 5,436 were metabolism-associated and 2,728 were stimulus response-associated that include 380 immunity-related unigenes. Expression profile analysis demonstrated that most genes involved in macromolecular metabolism, oxidative phosphorylation, detoxification and anti-oxidant defense were up-regulated by Cd exposure, whereas immunity-related genes were down-regulated, except the genes involved in phagocytosis were up-regulated. The current data indicate that Cd exposure alters gene expressions in a concentration-dependent manner. Therefore, our results provide the first comprehensive S.henanense transcriptome dataset, which is useful for biological and ecotoxicological studies on this crab and its related species at molecular level, and some key Cd-responsive genes may provide candidate biomarkers for monitoring aquatic pollution by heavy metals. PMID:26786678

  14. Transcriptome assembly and expression profiling of molecular responses to cadmium toxicity in hepatopancreas of the freshwater crab Sinopotamon henanense.

    PubMed

    Sun, Min; Ting Li, Yi; Liu, Yang; Chin Lee, Shao; Wang, Lan

    2016-01-01

    Cadmium (Cd) pollution is a serious global problem, which causes irreversible toxic effects on animals. Freshwater crab, Sinopotamon henanense, is a useful environmental indicator since it is widely distributed in benthic habitats whereby it tends to accumulate Cd and other toxicants. However, its molecular responses to Cd toxicity remain unclear. In this study, we performed transcriptome sequencing and gene expression analyses of its hepatopancreas with and without Cd treatments. A total of 7.78 G clean reads were obtained from the pooled samples, and 68,648 unigenes with an average size of 622 bp were assembled, in which 5,436 were metabolism-associated and 2,728 were stimulus response-associated that include 380 immunity-related unigenes. Expression profile analysis demonstrated that most genes involved in macromolecular metabolism, oxidative phosphorylation, detoxification and anti-oxidant defense were up-regulated by Cd exposure, whereas immunity-related genes were down-regulated, except the genes involved in phagocytosis were up-regulated. The current data indicate that Cd exposure alters gene expressions in a concentration-dependent manner. Therefore, our results provide the first comprehensive S.henanense transcriptome dataset, which is useful for biological and ecotoxicological studies on this crab and its related species at molecular level, and some key Cd-responsive genes may provide candidate biomarkers for monitoring aquatic pollution by heavy metals. PMID:26786678

  15. Transcriptome assembly and expression profiling of molecular responses to cadmium toxicity in hepatopancreas of the freshwater crab Sinopotamon henanense

    NASA Astrophysics Data System (ADS)

    Sun, Min; Ting Li, Yi; Liu, Yang; Chin Lee, Shao; Wang, Lan

    2016-01-01

    Cadmium (Cd) pollution is a serious global problem, which causes irreversible toxic effects on animals. Freshwater crab, Sinopotamon henanense, is a useful environmental indicator since it is widely distributed in benthic habitats whereby it tends to accumulate Cd and other toxicants. However, its molecular responses to Cd toxicity remain unclear. In this study, we performed transcriptome sequencing and gene expression analyses of its hepatopancreas with and without Cd treatments. A total of 7.78 G clean reads were obtained from the pooled samples, and 68,648 unigenes with an average size of 622 bp were assembled, in which 5,436 were metabolism-associated and 2,728 were stimulus response-associated that include 380 immunity-related unigenes. Expression profile analysis demonstrated that most genes involved in macromolecular metabolism, oxidative phosphorylation, detoxification and anti-oxidant defense were up-regulated by Cd exposure, whereas immunity-related genes were down-regulated, except the genes involved in phagocytosis were up-regulated. The current data indicate that Cd exposure alters gene expressions in a concentration-dependent manner. Therefore, our results provide the first comprehensive S.henanense transcriptome dataset, which is useful for biological and ecotoxicological studies on this crab and its related species at molecular level, and some key Cd-responsive genes may provide candidate biomarkers for monitoring aquatic pollution by heavy metals.

  16. Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Nanoparticle Titanium Dioxide

    EPA Science Inventory

    Identification of toxicity pathways linked to chemical -exposure is critical for a better understanding of biological effects of the exposure, toxic mechanisms, and for enhancement of the prediction of chemical toxicity and adverse health outcomes. To identify toxicity pathways a...

  17. Pharmacogenetic profile of xenobiotic enzyme metabolism in survivors of the Spanish toxic oil syndrome.

    PubMed Central

    Ladona, M G; Izquierdo-Martinez, M; Posada de la Paz, M P; de la Torre, R; Ampurdanés, C; Segura, J; Sanz, E J

    2001-01-01

    In 1981, the Spanish toxic oil syndrome (TOS) affected more than 20,000 people, and over 300 deaths were registered. Assessment of genetic polymorphisms on xenobiotic metabolism would indicate the potential metabolic capacity of the victims at the time of the disaster. Thus, impaired metabolic pathways may have contributed to the clearance of the toxicant(s) leading to a low detoxification or accumulation of toxic metabolites contributing to the disease. We conducted a matched case-control study using 72 cases (54 females, 18 males) registered in the Official Census of Affected Patients maintained by the Spanish government. Controls were nonaffected siblings (n =72) living in the same household in 1981 and nonaffected nonrelatives (n = 70) living in the neighborhood at that time, with no ties to TOS. Genotype analyses were performed to assess the metabolic capacity of phase I [cytochrome P450 1A1 (CYP1A1), CYP2D6] and phase II [arylamine N-acetyltransferase-2 (NAT2), GSTM1 (glutathione S-transferase M1) and GSTT1] enzyme polymorphisms. The degree of association of the five metabolic pathways was estimated by calculating their odds ratios (ORs) using conditional logistic regression analysis. In the final model, cases compared with siblings (72 pairs) showed no differences either in CYP2D6 or CYP1A1 polymorphisms, or in conjugation enzyme polymorphisms, whereas cases compared with the unrelated controls (70 pairs) showed an increase in NAT2 defective alleles [OR = 6.96, 95% confidence interval (CI), 1.46-33.20] adjusted by age and sex. Glutathione transferase genetic polymorphisms (GSTM1, GSTT1) showed no association with cases compared with their siblings or unrelated controls. These findings suggest a possible role of impaired acetylation mediating susceptibility in TOS. PMID:11335185

  18. Toxic element profiles in selected medicinal plants growing on serpentines in Bulgaria.

    PubMed

    Pavlova, Dolja; Karadjova, Irina

    2013-12-01

    Populations of medicinal plants growing on serpentines and their respective soils were analyzed for Fe, Ni, Mn, Cr, Co, Cd, Cu, Zn, and Pb using inductively coupled plasma atomic emission spectrometry. Aqua regia extraction and 0.43 M acetic acid extraction were used for the quantification of pseudototal and bioavailable fractions, respectively, of elements in soil and nitric acid digestion for determination of total element content in plants. Screening was performed to (1) document levels of toxic metals in herbs extensively used in preparation of products and standardized extracts, (2) compare accumulation abilities of ferns and seed plants, and (3) estimate correlations between metal content in plants and their soils. The toxic element content of plants varied from site to site on a large scale. The concentrations of Fe and Ni were elevated while those of Cu, Zn, and Pb were close to average values usually found in plants. The highest concentrations for almost all elements were measured in both Teucrium species. Specific differences in metal accumulation between ferns and seed plants were not recorded. The investigated species are not hyperaccumulators but can accumulate toxic elements, in some cases exceeding permissible levels proposed by the World Health Organization and European Pharmacopoeia. The harvesting of medicinal plants from serpentines could be hazardous to humans. PMID:24170367

  19. Towards Profiles of Resistance Development and Toxicity for the Small Cationic Hexapeptide RWRWRW-NH2.

    PubMed

    Wenzel, Michaela; Prochnow, Pascal; Mowbray, Catherine; Vuong, Cuong; Höxtermann, Stefan; Stepanek, Jennifer J; Albada, H Bauke; Hall, Judith; Metzler-Nolte, Nils; Bandow, Julia E

    2016-01-01

    RWRWRW-NH2 (MP196) is an amphipathic hexapeptide that targets the bacterial cytoplasmic membrane and inhibits cellular respiration and cell wall synthesis. In previous studies it showed promising activity against Gram-positive bacteria and no significant cytotoxicity or hemolysis. MP196 is therefore used as lead structure for developing more potent antibiotic derivatives. Here we present a more comprehensive study on the parent peptide MP196 with regard to clinically relevant parameters. We found that MP196 acts rapidly bactericidal killing 97% of initial CFU within 10 min at two times MIC. We were unable to detect resistance in standard 24 and 48 h resistance frequency assays. However, MP196 was effective against some but not all MRSA and VISA strains. Serum binding of MP196 was intermediate and we confirmed its low toxicity against mammalian cell lines. MP196 did neither induce NFκB activation nor cause an increase in IL8 levels at 250 μg/mL, and no IgE-dependent activation of basophil granulocytes was detected at 500 μg/mL. Yet, MP196 demonstrated acute toxicity in mice upon injection into the blood stream. Phase contrast microscopy of mouse blood treated with MP196 revealed a shrinking of erythrocytes at 250 μg/mL and severe morphological changes and lysis of erythrocytes at 500 μg/mL. These data suggest that MP196 derivatization directed at further lowering hemolysis could be instrumental in overcoming acute toxicity. The assessment of hemolysis is a critical step in the evaluation of the clinical potential of promising antimicrobial peptides and should be accompanied by microscopy-based morphological analysis of blood cells. PMID:27617260

  20. Towards Profiles of Resistance Development and Toxicity for the Small Cationic Hexapeptide RWRWRW-NH2

    PubMed Central

    Wenzel, Michaela; Prochnow, Pascal; Mowbray, Catherine; Vuong, Cuong; Höxtermann, Stefan; Stepanek, Jennifer J.; Albada, H. Bauke; Hall, Judith; Metzler-Nolte, Nils; Bandow, Julia E.

    2016-01-01

    RWRWRW-NH2 (MP196) is an amphipathic hexapeptide that targets the bacterial cytoplasmic membrane and inhibits cellular respiration and cell wall synthesis. In previous studies it showed promising activity against Gram-positive bacteria and no significant cytotoxicity or hemolysis. MP196 is therefore used as lead structure for developing more potent antibiotic derivatives. Here we present a more comprehensive study on the parent peptide MP196 with regard to clinically relevant parameters. We found that MP196 acts rapidly bactericidal killing 97% of initial CFU within 10 min at two times MIC. We were unable to detect resistance in standard 24 and 48 h resistance frequency assays. However, MP196 was effective against some but not all MRSA and VISA strains. Serum binding of MP196 was intermediate and we confirmed its low toxicity against mammalian cell lines. MP196 did neither induce NFκB activation nor cause an increase in IL8 levels at 250 μg/mL, and no IgE-dependent activation of basophil granulocytes was detected at 500 μg/mL. Yet, MP196 demonstrated acute toxicity in mice upon injection into the blood stream. Phase contrast microscopy of mouse blood treated with MP196 revealed a shrinking of erythrocytes at 250 μg/mL and severe morphological changes and lysis of erythrocytes at 500 μg/mL. These data suggest that MP196 derivatization directed at further lowering hemolysis could be instrumental in overcoming acute toxicity. The assessment of hemolysis is a critical step in the evaluation of the clinical potential of promising antimicrobial peptides and should be accompanied by microscopy-based morphological analysis of blood cells.

  1. An Unusual Case of Central Retinal Vein Occlusion and Review of the Toxicity Profile of Regorafenib in GIST Patients.

    PubMed

    Schvartsman, Gustavo; Wagner, Michael J; Zobniw, Chrystia M; Trinh, Van Anh; Patel, Shreyaskumar; Somaiah, Neeta

    2016-08-01

    Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract with around 5000 new cases per year. Outcomes for patients with GIST dramatically improved after the development of tyrosine kinase inhibitors targeted against the aberrant signaling pathways that drive GIST oncogenesis. Majority of patients derive benefit from first-line imatinib, and the type of driver mutation is predictive of response. However, almost half of the patients eventually develop resistance to initial targeted therapy and further lines of treatment do not have the same impact. Regorafenib is an oral multi-kinase inhibitor approved as a third-line therapy for advanced GIST and though its efficacy is limited in comparison to imatinib, it has activity across the various driver mutation categories in GIST even in the setting of imatinib resistance. Herein, we describe a case of central retinal vein occlusion (CRVO) secondary to regorafenib and review regorafenib's efficacy and toxicity profile. PMID:27319943

  2. Toxicity Profiles In Vivo in Mice and Antitumour Activity in Tumour-Bearing Mice of Di- and Triorganotin Compounds

    PubMed Central

    Willem, R.; Dalil, H.; de Vos, D.; Kuiper, C. M.; Peters, G. J.

    1998-01-01

    The in vivo toxicity profiles in mice and the antitumour activity in tumour bearing mice were screened for four di-n-butyltin and five triorganotin carboxylates, di-n-butyltin diterebate (5), bis(phenylacetate) (6), bis(deoxycholate) (7), bis(lithocholate) (8), tri-n-butyltin terebate (9), cinnamate (10), and triphenyltin terebate (11). At their maximum tolerated dosis (MTD), no antitumour effect (T/C ~1) was observed for the compounds 5, 7, 9, 10 and 11. The compounds 6 (T/C = 0.51) and 8 (T/C = 0.42) showed clear antitumour activity after single dose administration and might therefore be of interest for further antitumour activity studies. PMID:18475827

  3. In vivo toxicity of nano-alumina on mice neurobehavioral profiles and the potential mechanisms.

    PubMed

    Zhang, Q L; Li, M Q; Ji, J W; Gao, F P; Bai, R; Chen, C Y; Wang, Z W; Zhang, C; Niu, Q

    2011-01-01

    The rapid development and expanding applications of nanotechnology have led to enhanced exposure of human body to nanoparticles. It is, therefore, necessary to address the safety issue via rigorous toxicological evaluation and to understand the underlying interaction mechanism. However, only a few studies to date have evaluated the safety of nano-sized materials and their potential adverse effects on biological systems. In this study, we sought to investigate the potential toxicity of aluminum oxide (alumina) nanoparticles in ICR strained mice, focusing on potential neurobehavioral defects and the possible mechanisms. The results demonstrated that nano-alumina impaired neurobehavioral functions, including lengthened escape latency, shorter time spent in the target quadrant and reductions in the number of platform crossing. In addition, it induced cell necrosis and apoptosis, which were likely mediated by the reduction of MMP and ROS, and the induction of the caspase-3 gene. Our results implicated that mitochondrial impairment plays a key role in neurotoxicity of nano-alumina, sequent oxidative damage and neural cell loss, especially necrosis, may be direct causes for the neurobehavioral defects. Collectively, nano-alumina presents a strong pro-cell death effect on ICR mice in vivo, suggesting that nano-alumina may serve as an inducer for neural toxicology. Findings in the present study indicating that surface chemical characteristics and nanoscale sizes of nano-alumina could co-contribute significantly to neurotoxicity. The impaired neurobehavioral patterns indicate that nano-alumina particles are more toxic to the cerebrum than those of nano-carbon with the same nanoparticle size and micro-alumina with the same surface chemical characteristics. PMID:21329562

  4. Genomic and proteomic profiling of responses to toxic metals in human lung cells.

    PubMed Central

    Andrew, Angeline S; Warren, Amy J; Barchowsky, Aaron; Temple, Kaili A; Klei, Linda; Soucy, Nicole V; O'Hara, Kimberley A; Hamilton, Joshua W

    2003-01-01

    Examining global effects of toxic metals on gene expression can be useful for elucidating patterns of biological response, discovering underlying mechanisms of toxicity, and identifying candidate metal-specific genetic markers of exposure and response. Using a 1,200 gene nylon array, we examined changes in gene expression following low-dose, acute exposures of cadmium, chromium, arsenic, nickel, or mitomycin C (MMC) in BEAS-2B human bronchial epithelial cells. Total RNA was isolated from cells exposed to 3 M Cd(II) (as cadmium chloride), 10 M Cr(VI) (as sodium dichromate), 3 g/cm2 Ni(II) (as nickel subsulfide), 5 M or 50 M As(III) (as sodium arsenite), or 1 M MMC for 4 hr. Expression changes were verified at the protein level for several genes. Only a small subset of genes was differentially expressed in response to each agent: Cd, Cr, Ni, As (5 M), As (50 M), and MMC each differentially altered the expression of 25, 44, 31, 110, 65, and 16 individual genes, respectively. Few genes were commonly expressed among the various treatments. Only one gene was altered in response to all four metals (hsp90), and no gene overlapped among all five treatments. We also compared low-dose (5 M, noncytotoxic) and high-dose (50 M, cytotoxic) arsenic treatments, which surprisingly, affected expression of almost completely nonoverlapping subsets of genes, suggesting a threshold switch from a survival-based biological response at low doses to a death response at high doses. PMID:12760830

  5. Comprehensive microRNA profiling in acetaminophen toxicity identifies novel circulating biomarkers for human liver and kidney injury.

    PubMed

    Vliegenthart, A D B; Shaffer, J M; Clarke, J I; Peeters, L E J; Caporali, A; Bateman, D N; Wood, D M; Dargan, P I; Craig, D G; Moore, J K; Thompson, A I; Henderson, N C; Webb, D J; Sharkey, J; Antoine, D J; Park, B K; Bailey, M A; Lader, E; Simpson, K J; Dear, J W

    2015-01-01

    Our objective was to identify microRNA (miRNA) biomarkers of drug-induced liver and kidney injury by profiling the circulating miRNome in patients with acetaminophen overdose. Plasma miRNAs were quantified in age- and sex-matched overdose patients with (N = 27) and without (N = 27) organ injury (APAP-TOX and APAP-no TOX, respectively). Classifier miRNAs were tested in a separate cohort (N = 81). miRNA specificity was determined in non-acetaminophen liver injury and murine models. Sensitivity was tested by stratification of patients at hospital presentation (N = 67). From 1809 miRNAs, 75 were 3-fold or more increased and 46 were 3-fold or more decreased with APAP-TOX. A 16 miRNA classifier model accurately diagnosed APAP-TOX in the test cohort. In humans, the miRNAs with the largest increase (miR-122-5p, miR-885-5p, miR-151a-3p) and the highest rank in the classifier model (miR-382-5p) accurately reported non-acetaminophen liver injury and were unaffected by kidney injury. miR-122-5p was more sensitive than ALT for reporting liver injury at hospital presentation, especially combined with miR-483-3p. A miRNA panel was associated with human kidney dysfunction. In mice, miR-122-5p, miR-151a-3p and miR-382-5p specifically reported APAP toxicity - being unaffected by drug-induced kidney injury. Profiling of acetaminophen toxicity identified multiple miRNAs that report acute liver injury and potential biomarkers of drug-induced kidney injury. PMID:26489516

  6. Exploring the zebrafish embryo as an alternative model for the evaluation of liver toxicity by histopathology and expression profiling.

    PubMed

    Driessen, Marja; Kienhuis, Anne S; Pennings, Jeroen L A; Pronk, Tessa E; van de Brandhof, Evert-Jan; Roodbergen, Marianne; Spaink, Herman P; van de Water, Bob; van der Ven, Leo T M

    2013-05-01

    The whole zebrafish embryo model (ZFE) has proven its applicability in developmental toxicity testing. Since functional hepatocytes are already present from 36 h post fertilization onwards, whole ZFE have been proposed as an attractive alternative to mammalian in vivo models in hepatotoxicity testing. The goal of the present study is to further underpin the applicability of whole ZFE for hepatotoxicity testing by combining histopathology and next-generation sequencing-based gene expression profiling. To this aim, whole ZFE and adult zebrafish were exposed to a set of hepatotoxic reference compounds. Histopathology revealed compound and life-stage-specific effects indicative of toxic injury in livers of whole ZFE and adult zebrafish. Next-generation sequencing (NGS) was used to compare transcript profiles in pooled individual RNA samples of whole ZFE and livers of adult zebrafish. This revealed that hepatotoxicity-associated expression can be detected beyond the overall transcription noise in the whole embryo. In situ hybridization verified liver specificity of selected highly expressed markers in whole ZFE. Finally, cyclosporine A (CsA) was used as an illustrative case to support applicability of ZFE in hepatotoxicity testing by comparing CsA-induced gene expression between ZFE, in vivo mouse liver and HepaRG cells on the levels of single genes, pathways and transcription factors. While there was no clear overlap on single gene level between the whole ZFE and in vivo mouse liver, strong similarities were observed between whole ZFE and in vivo mouse liver in regulated pathways related to hepatotoxicity, as well as in relevant overrepresented transcription factors. In conclusion, both the use of NGS of pooled RNA extracts analysis combined with histopathology and traditional microarray in single case showed the potential to detect liver-related genes and processes within the transcriptome of a whole zebrafish embryo. This supports the applicability of the whole ZFE

  7. Identification of 1- and 3-methylhistidine as biomarkers of skeletal muscle toxicity by nuclear magnetic resonance-based metabolic profiling.

    PubMed

    Aranibar, Nelly; Vassallo, Jeffrey D; Rathmacher, John; Stryker, Steve; Zhang, Yingru; Dai, Jun; Janovitz, Evan B; Robertson, Don; Reily, Michael; Lowe-Krentz, Linda; Lehman-McKeeman, Lois

    2011-03-01

    Nuclear magnetic resonance (NMR)-based metabolomic profiling identified urinary 1- and 3-methylhistidine (1- and 3-MH) as potential biomarkers of skeletal muscle toxicity in Sprague-Dawley rats following 7 and 14 daily doses of 0.5 or 1mg/kg cerivastatin. These metabolites were highly correlated to sex-, dose- and time-dependent development of cerivastatin-induced myotoxicity. Subsequently, the distribution and concentration of 1- and 3-MH were quantified in 18 tissues by gas chromatography-mass spectrometry. The methylhistidine isomers were most abundant in skeletal muscle with no fiber or sex differences observed; however, 3-MH was also present in cardiac and smooth muscle. In a second study, rats receiving 14 daily doses of 1mg/kg cerivastatin (a myotoxic dose) had 6- and 2-fold elevations in 1- and 3-MH in urine and had 11- and 3-fold increases in 1- and 3-MH in serum, respectively. Selectivity of these potential biomarkers was tested by dosing rats with the cardiotoxicant isoproterenol (0.5mg/kg), and a 2-fold decrease in urinary 1- and 3-MH was observed and attributed to the anabolic effect on skeletal muscle. These findings indicate that 1- and 3-MH may be useful urine and serum biomarkers of drug-induced skeletal muscle toxicity and hypertrophy in the rat, and further investigation into their use and limitations is warranted. PMID:21094120

  8. Proteome Profiling of BEAS-2B Cells Treated with Titanium Dioxide Reveals Potential Toxicity of and Detoxification Pathways for Nanomaterial

    EPA Science Inventory

    Oxidative stress is known to play important roles in nanomaterial-induced toxicities. However, the proteins and signaling pathways associated with nanomaterial-mediated oxidative stress and toxicity are largely unknown. To identify oxidative stress-responding toxicity pathways an...

  9. Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Titanium Dioxide Nanoparticles

    EPA Science Inventory

    Oxidative stress is known to play important roles in engineered nanomaterial induced cellular toxicity. However, the proteins and signaling pathways associated with the engineered nanomaterial mediated oxidative stress and toxicity are largely unknown. To identify these toxicity ...

  10. Third and fourth generation fluoroquinolone antibacterials: a systematic review of safety and toxicity profiles.

    PubMed

    Sousa, Joana; Alves, Gilberto; Fortuna, Ana; Falcão, Amilcar

    2014-01-01

    In the last decade, several third and fourth generation fluoroquinolones (FQs) have been approved for clinical use. These new agents exhibit a more potent and broader-spectrum antibacterial activity and improved pharmacokinetic properties in comparison to the earlier FQs. Although new FQs are generally safe and well tolerated, moderate-to-severe toxicity events have been reported for some of them, leading to their restriction, suspension or even withdrawal from the market. The most common FQ-related adverse effects (AEs) are usually mild and involve the gastrointestinal tract (e.g. nausea and diarrhea) and the central nervous system (e.g. headache and dizziness). Uncommon, but severe AEs (e.g. arthropathy, QTc interval prolongation, dysglycaemia and phototoxicity) and idiosyncratic reactions (e.g. hepatitis and hemolytic anemia) have also been reported and will be discussed throughout this paper. The evidence currently available suggests that AEs can be inherent to the FQ class or can be associated with a particular chemical moiety of the molecular structure of each FQ, thus varying in frequency, severity and nature. The main goal of this review is to provide a systematic evaluation of safety and tolerability data of the newer FQs with emphasis on those currently marketed. PMID:24410307

  11. Preclinical Reproductive and Developmental Toxicity Profile of a Glycine Transporter Type 1 (Glyt1) Inhibitor.

    PubMed

    Barrow, Paul; Parrott, Neil; Alberati, Daniela; Paehler, Axel; Koerner, Annette

    2016-06-01

    Bitopertin is a glycine type 1 (GlyT1) inhibitor intended for the treatment of psychiatric disorders. The principle adverse effect in the regulatory reproductive toxicity studies was peri-natal pup death when rat dams were treated during parturition at a dose resulting in five-times the human therapeutic exposure (AUC). Cessation of dosing two days before parturition prevented the pup deaths. Investigatory experiments and pharmacokinetic modelling suggested that the neonatal mortality was related to transplacental passage of bitopertin leading to high systemic levels in the newborn pups. Brain levels of bitopertin in the rat fetus and neonate were two-fold higher than in the mother. As illustrated by knock-out mice models, GlyT1 function is essential for neonatal pup survival in rodents, but is not necessary for normal prenatal morphological development. The glycine transport systems are immature at birth in the rat, but are functionally well-developed in the human newborn. While the relevance to humans of the neonatal mortality seen in rats following late gestational exposure is unknown, bitopertin would not be recommended for use during late pregnancy unless the anticipated benefit for the mother outweighs the potential risk to the newborn. PMID:27221585

  12. PROFILING GENE EXPRESSION IN HUMAN H295R ADRENOCORTICAL CARCINOMA CELLS AND RAT TESTES TO IDENTIFY PATHWAYS OF TOXICITY FOR CONAZOLE FUNGICIDES

    EPA Science Inventory

    Profiling Gene Expression in Human H295R Adrenocortical Carcinoma Cells and Rat Testes to Identify Pathways of Toxicity for Conazole Fungicides
    Ren1, H., Schmid1, J., Retief2, J., Turpaz2, Y.,Zhang3, X.,Jones3, P., Newsted3, J.,Giesy3, J., Wolf1, D.,Wood1, C., Bao1, W., Dix1, ...

  13. Profiles of paralytic shellfish toxins in bivalves of low and elevated toxicities following exposure to Gymnodinium catenatum blooms in Portuguese estuarine and coastal waters.

    PubMed

    Botelho, Maria João; Vale, Carlos; Ferreira, João Gomes

    2015-11-01

    Profiles of paralytic shellfish toxins (PSTs) were examined in 405 composite samples of Mytilus spp., Cerastoderma edule, Donax trunculus and Spisula solida collected between 2007 and 2012 from natural production areas in two estuaries (Aveiro and Mondego), two coastal lagoons (Óbidos and Formosa), and three open coastal areas (Aguda, Comporta and Culatra). Toxin concentrations were obtained from the biotoxin monitoring programme database. Episodes of PST toxicity in Portugal have been associated with Gymnodinium catenatum blooms. Toxin profiles for each species showed no trend over the surveyed years. In general, profiles differ only slightly among areas, except for Óbidos. However, toxin profiles in bivalves varied between low and elevated toxicities, corresponding to below and above the PST regulatory limit, respectively. The ratio R1=(C1+2):B1, which were the main toxins produced by G. catenatum cells, decreased considerably between elevated and low toxicity cockles, indicating the elimination of C1+2 or conversion of compounds into B1. R2=[(dcSTX)+(dcGTX2+3)]:[(C1+2)+(B1)], which represents the ratio of minor to major toxins in G. catenatum cells, increased substantially in wedge clams (D. trunculus) of low toxicity and less markedly in cockles (C. edule) and mussels (Mytilus spp.). These differences are interpreted as the predominance of a biotransformation phase after exposure to the algal bloom. The toxin profile of surf clams (S. solida) was dominated by decarbamoyl compounds, reflecting intense biotransformation during exposure to blooms. The higher ratio R2 in low toxicity samples suggests that elimination of the produced decarbamoyl toxins was slower than biotransformation. PMID:25616737

  14. Carbonyl emission and toxicity profile of diesel blends with an animal-fat biodiesel and a tire pyrolysis liquid fuel.

    PubMed

    Ballesteros, R; Guillén-Flores, J; Martínez, J D

    2014-02-01

    In this paper, two diesel fuels, an animal-fat biodiesel and two diesel blends with the animal-fat biodiesel (50vol.%) and with a tire pyrolysis liquid (TPL) fuel (5vol.%) have been tested in a 4-cylinder, 4-stroke, turbocharged, intercooled, 2.0L Nissan diesel automotive engine (model M1D) with common-rail injection system and diesel oxidation catalyst (DOC). Carbonyl emissions have been analyzed both before and after DOC and specific reactivity of carbonyl profile has been calculated. Carbonyl sampling was carried out by means of a heated line, trapping the gas in 2,4-DNPH cartridges. The eluted content was then analyzed in an HPLC system, with UV-VIS detection. Results showed, on the one hand, an increase in carbonyl emissions with the biodiesel fraction in the fuel. On the other hand, the addition of TPL to diesel also increased carbonyl emissions. These trends were occasionally different if the emissions were studied after the DOC, as it seems to be selectivity during the oxidation process. The specific reactivity was also studied, finding a decrease with the oxygen content within the fuel molecule, although the equivalent ozone emissions slightly increased with the oxygen content. Finally, the emissions toxicity was also studied, comparing them to different parameters defined by different organizations. Depending on the point of study, emissions were above or below the established limits, although acrolein exceeded them as it has the least permissive values. PMID:24184046

  15. Intraventricular etoposide safety and toxicity profile in children and young adults with refractory or recurrent malignant brain tumors.

    PubMed

    Pajtler, Kristian W; Tippelt, Stephan; Siegler, Nele; Reichling, Stefanie; Zimmermann, Martina; Mikasch, Ruth; Bode, Udo; Gnekow, Astrid; Pietsch, Torsten; Benesch, Martin; Rutkowski, Stefan; Fleischhack, Gudrun

    2016-07-01

    Systemic administration of etoposide is effective in treating metastatic, recurrent or refractory brain tumors, but penetration into the cerebrospinal fluid is extremely poor. This study was designed to determine the safety and toxicity profile of intraventricular etoposide administration and was affiliated with the prospective, multicenter, nonblinded, nonrandomized, multi-armed HIT-REZ-97 trial. The study enrolled 68 patients, aged 1.1-34.6 (median age 11 years). Adverse events that could possibly be related to intraventricular etoposide therapy were documented and analyzed. Intraventricular etoposide was simultaneously administered with either oral or intravenous chemotherapy in 426 courses according to three major schedules varying in dosing (0.25-1 mg), frequency of administration (bolus injection, every 12 or 24 h), course duration (5-10 days) and length of interval between courses (2-5 weeks). Potential treatment-related adverse effects included transient headache, seizures, infection of the reservoir, nausea and neuropsychological symptoms. Hematological side effects were not observed. One patient, with history of multiple prior therapies, who received long-term intraventricular and oral etoposide treatment developed acute myeloid leukemia as a secondary malignancy. Overall intraventricular etoposide is well tolerated. The results of this study have warranted a phase II trial to determine the effectiveness of this regimen in disease stages with very limited therapeutic options. PMID:27147083

  16. Development of a beef flavor lexicon and its application to compare the flavor profile and consumer acceptance of rib steaks from grass- or grain-fed cattle.

    PubMed

    Maughan, Curtis; Tansawat, Rossarin; Cornforth, Daren; Ward, Robert; Martini, Silvana

    2012-01-01

    Ten panelists were selected from the local community to develop a meat lexicon composed of 18 terms that describe flavor attributes found in red meats. This flavor lexicon was used to compare the flavor profile of meat from beef cattle finished on grass or grain. Steaks from grass-fed animals were significantly (P<0.05) higher in barny, bitter, gamey, and grassy flavor, and lower in juicy and umami notes. Gamey, barny, bitter and grassy were some of the attributes inversely correlated to the degree of liking of the meat and therefore can be classified as "negative" attributes. Brothy, umami, roast beef, juicy, browned, fatty and salty are some of the attributes positively correlated to the degree of liking of beef and therefore can be identified as attributes that drive consumers' acceptance. Steaks from grass-fed cattle were rated by consumers as slightly liked (6.08 on a 9-point scale), while steaks from grain-fed animals were rated as moderately liked (7.05 on a 9-point scale). PMID:21703775

  17. Longitudinal stability of social competence indicators in a Portuguese sample: Q-sort profiles of social competence, measures of social engagement, and peer sociometric acceptance.

    PubMed

    Santos, António J; Vaughn, Brian E; Peceguina, Inês; Daniel, João R

    2014-03-01

    This study examines the temporal stability (over 3 years) of individual differences in 3 domains relevant to preschool children's social competence: social engagement/motivation, profiles of behavior and personality attributes characteristic of socially competent young children, and peer acceptance. Each domain was measured with multiple indicators. Sociometric status categories (Asher & Dodge, 1986) and reciprocated friendships were derived from sociometric data. Composites for social competence domains were significantly associated across all time points. Within age-periods, social competence domains were associated with both sociometric and friendship status categories; however, neither sociometric status nor reciprocated friendships were stable over time. Nevertheless, analyses examining the social competence antecedents to reciprocated friendship at age-4 and age-5 suggested that more socially competent children in the prior year were more likely to have a reciprocated friendship in the current year. Popular and rejected sociometric status categories were also associated with social competence indicators in prior years, but this was most clearly seen at age-5. PMID:24015691

  18. Activity-guided chemo toxic profiling of Cassia occidentalis (CO) seeds: detection of toxic compounds in body fluids of CO-exposed patients and experimental rats.

    PubMed

    Panigrahi, Gati Krushna; Ch, Ratnasekhar; Mudiam, Mohana K R; Vashishtha, Vipin M; Raisuddin, S; Das, Mukul

    2015-06-15

    Our prior studies have shown an association between the deaths of children and consumption of Cassia occidentalis (CO) seeds. However, the chemicals responsible for the CO poisoning are not known. Therefore, the present study was designed to identify the key moieties in CO seeds and their cytotoxicity in rat primary hepatocytes and HepG2 cells. Activity-guided sequential extraction and fractionation of the seeds followed by GC-MS analysis identified the toxic compounds in the CO seeds. These identified compounds were subsequently detected and quantified in blood and urine samples from CO-exposed rats and CO poisoning human study cases. GC-MS analysis of different fractions of methanol extracts of CO seeds revealed the presence of five anthraquinones (AQs), viz. physcion, emodin, rhein, aloe-emodin, and chrysophanol. Interestingly, these AQs were detected in serum and urine samples from the study cases and CO-exposed rats. Cytotoxicity analysis of the above AQs in rat primary hepatocytes and HepG2 cells revealed that rhein is the most toxic moiety, followed by emodin, aloe-emodin, physcion, and chrysophanol. These studies indicate that AQ aglycones are responsible for producing toxicity, which may be associated with symptoms of hepatomyoencephalopathy in CO poisoning cases. PMID:25915165

  19. Profiling Chemicals Based on Chronic Toxicity Results from the U.S. EPA ToxRef Database

    EPA Science Inventory

    Thirty years of pesticide registration toxicity data have been historically stored as hardcopy and scanned documents by the U.S. Environmental Protection Agency (EPA) . A significant portion of these data have now been processed into standardized and structured toxicity data with...

  20. Profiles.

    ERIC Educational Resources Information Center

    School Arts, 1979

    1979-01-01

    Profiles seven Black, Native American, and Chicano artists and art teachers: Hale A. Woodruff, Allan Houser, Luis Jimenez, Betrand D. Phillips, James E. Pate, I, and Fernando Navarro. This article is part of a theme issue on multicultural art. (SJL)

  1. [Toxicity and toxin profile of scavenging and carnivorous gastropods from the coastal waters of Okinawa Prefecture, Japan].

    PubMed

    Taniyama, Shigeto; Takatani, Tomohiro; Sorimachi, Taiki; Sagara, Takefumi; Kubo, Hirofumi; Oshiro, Naomasa; Ono, Kaname; Xiao, Ning; Tachibana, Katsuyasu; Arakawa, Osamu

    2013-01-01

    From January to June 2009, a total of 64 gastropod specimens of 15 species were collected from the coastal waters of Okinawa Prefecture, Japan, and examined for toxicity by means of mouse bioassay. Among the specimens tested, 5 species, Nassarius glans, Nassariuscoronatus, Olivaannulata, Oliva concavospira and Zeuxis sp., were toxic. The toxicity scores of N. glans were very high; 39.6-461 MU/g in muscle, and 98.6-189 MU/g in viscera including digestive gland, followed by Zeuxis sp. (12.7 MU/g in whole body), N. coronatus (5.64-11.1 MU/g in whole body), O. annulata (10.8 MU/g in the whole body), O. concavospira (6.65 MU/g in the muscle). Liquid chromatography/mass spectrometry (LC-MS) revealed that the major toxic component was tetrodotoxin (TTX), which accounting for 13-82% of the total toxicity. As for the remaining toxicity in the case of N. glans, 4,9-anhydroTTX, 4-epiTTX and 11-oxoTTX were contributors. Moreover, Niotha albescens showed no toxicity (less than 10 MU/g) in mouse bioassay, but TTX (5.08 MU/g) was detected by LC-MS. Paralytic shellfish poison was not detected in any of the specimens by high-performance liquid chromatography with fluorometric detection (HPLC-FLD). PMID:23470873

  2. Toxic substances handbook

    NASA Technical Reports Server (NTRS)

    Junod, T. L.

    1979-01-01

    Handbook, published in conjunction with Toxic Substances Alert Program at NASA Lewis Research Center, profiles 187 toxic chemicals in their relatively pure states and include 27 known or suspected carcinogens.

  3. PROFILE OF TOXIC RESPONSE TO SEDIMENTS USING WHOLE-ANIMAL AND IN VITRO SUBMITOCHONDRIAL PARTICLE (SMP) ASSAYS

    EPA Science Inventory

    A rapid bioassy for monitoring acute toxicity of wastewater, ground water, and soil and sediment extracts using submitochondrial particles (SMP) has been developed. The assay utilizes the mitochondrial electron transfer enzyme complex present in all eukaryotic cells. Prior develo...

  4. Comparison of hepatic transcription profiles of locked ribonucleic acid antisense oligonucleotides: evidence of distinct pathways contributing to non-target mediated toxicity in mice.

    PubMed

    Kakiuchi-Kiyota, Satoko; Koza-Taylor, Petra H; Mantena, Srinivasa R; Nelms, Linda F; Enayetallah, Ahmed E; Hollingshead, Brett D; Burdick, Andrew D; Reed, Lori A; Warneke, James A; Whiteley, Lawrence O; Ryan, Anne M; Mathialagan, Nagappan

    2014-03-01

    Development of LNA gapmers, antisense oligonucleotides used for efficient inhibition of target RNA expression, is limited by non-target mediated hepatotoxicity issues. In the present study, we investigated hepatic transcription profiles of mice administered non-toxic and toxic LNA gapmers. After repeated administration, a toxic LNA gapmer (TS-2), but not a non-toxic LNA gapmer (NTS-1), caused hepatocyte necrosis and increased serum alanine aminotransferase levels. Microarray data revealed that, in addition to gene expression patterns consistent with hepatotoxicity, 17 genes in the clathrin-mediated endocytosis (CME) pathway were altered in the TS-2 group. TS-2 significantly down-regulated myosin 1E (Myo1E), which is involved in release of clathrin-coated pits from plasma membranes. To map the earliest transcription changes associated with LNA gapmer-induced hepatotoxicity, a second microarray analysis was performed using NTS-1, TS-2, and a severely toxic LNA gapmer (HTS-3) at 8, 16, and 72 h following a single administration in mice. The only histopathological change observed was minor hepatic hypertrophy in all LNA groups across time points. NTS-1, but not 2 toxic LNA gapmers, increased immune response genes at 8 and 16 h but not at 72 h. TS-2 significantly perturbed the CME pathway only at 72 h, while Myo1E levels were decreased at all time points. In contrast, HTS-3 modulated DNA damage pathway genes at 8 and 16 h and also modulated the CME pathway genes (but not Myo1E) at 16 h. Our results may suggest that different LNAs modulate distinct transcriptional genes and pathways contributing to non-target mediated hepatotoxicity in mice. PMID:24336348

  5. Comparative toxicity profiles of Plumbago zeylanica L. root petroleum ether, acetone and hydroalcoholic extracts in Wistar rats

    PubMed Central

    Kumar, Dushyant; Patil, Paragouda A.; Roy, Subarna; Kholkute, Sanjiv D.; Hegde, Harsha V.; Nair, Vinod

    2015-01-01

    Introduction: The root of Plumbago zeylanica Linn. is used in traditional medicine for the treatment of chronic inflammatory diseases and various disorders. The toxicity of this plant has not yet been extensively evaluated. Aim: To evaluate and compare the toxicity of P. zeylanica root petroleum ether (PZPE), acetone (PZAC), and the hydroalcoholic (PZHY) extracts. Materials and Methods: The acute and sub-acute toxicities of extracts were evaluated according to OECD guidelines 425 and 407, respectively in female rats. Results: PZPE was more toxic than PZAC and PZHA, based on LD50 values of 93.45, 928.4, and 928.4 mg/kg, respectively. This potency difference directly correlates with the plumbagin content of extracts. With regard to sub-acute toxicity, a significant increase in organ weights (liver, adrenal glands, and/or heart) was observed in PZPE and PZAC treated groups. All extracts produced a significant increase in serum aspartate aminotransferase and urea, and PZAC produced a significant increase in serum creatinine as compared to control. A decrease in hematocrit was observed in the highest dose PZPE group, and a decrease in leukocytes was observed in all PZAC groups. Hepatic and renal changes were observed in all extract treated groups. Conclusion: The findings of our study, thus demonstrate that liver and kidney are the primary organs being adversely affected following sub-acute administration of P. zeylanica root extract in rats. PMID:27313422

  6. Nephron Toxicity Profiling via Untargeted Metabolome Analysis Employing a High Performance Liquid Chromatography-Mass Spectrometry-based Experimental and Computational Pipeline*

    PubMed Central

    Ranninger, Christina; Rurik, Marc; Limonciel, Alice; Ruzek, Silke; Reischl, Roland; Wilmes, Anja; Jennings, Paul; Hewitt, Philip; Dekant, Wolfgang; Kohlbacher, Oliver; Huber, Christian G.

    2015-01-01

    Untargeted metabolomics has the potential to improve the predictivity of in vitro toxicity models and therefore may aid the replacement of expensive and laborious animal models. Here we describe a long term repeat dose nephrotoxicity study conducted on the human renal proximal tubular epithelial cell line, RPTEC/TERT1, treated with 10 and 35 μmol·liter−1 of chloroacetaldehyde, a metabolite of the anti-cancer drug ifosfamide. Our study outlines the establishment of an automated and easy to use untargeted metabolomics workflow for HPLC-high resolution mass spectrometry data. Automated data analysis workflows based on open source software (OpenMS, KNIME) enabled a comprehensive and reproducible analysis of the complex and voluminous metabolomics data produced by the profiling approach. Time- and concentration-dependent responses were clearly evident in the metabolomic profiles. To obtain a more comprehensive picture of the mode of action, transcriptomics and proteomics data were also integrated. For toxicity profiling of chloroacetaldehyde, 428 and 317 metabolite features were detectable in positive and negative modes, respectively, after stringent removal of chemical noise and unstable signals. Changes upon treatment were explored using principal component analysis, and statistically significant differences were identified using linear models for microarray assays. The analysis revealed toxic effects only for the treatment with 35 μmol·liter−1 for 3 and 14 days. The most regulated metabolites were glutathione and metabolites related to the oxidative stress response of the cells. These findings are corroborated by proteomics and transcriptomics data, which show, among other things, an activation of the Nrf2 and ATF4 pathways. PMID:26055719

  7. Nephron Toxicity Profiling via Untargeted Metabolome Analysis Employing a High Performance Liquid Chromatography-Mass Spectrometry-based Experimental and Computational Pipeline.

    PubMed

    Ranninger, Christina; Rurik, Marc; Limonciel, Alice; Ruzek, Silke; Reischl, Roland; Wilmes, Anja; Jennings, Paul; Hewitt, Philip; Dekant, Wolfgang; Kohlbacher, Oliver; Huber, Christian G

    2015-07-31

    Untargeted metabolomics has the potential to improve the predictivity of in vitro toxicity models and therefore may aid the replacement of expensive and laborious animal models. Here we describe a long term repeat dose nephrotoxicity study conducted on the human renal proximal tubular epithelial cell line, RPTEC/TERT1, treated with 10 and 35 μmol·liter(-1) of chloroacetaldehyde, a metabolite of the anti-cancer drug ifosfamide. Our study outlines the establishment of an automated and easy to use untargeted metabolomics workflow for HPLC-high resolution mass spectrometry data. Automated data analysis workflows based on open source software (OpenMS, KNIME) enabled a comprehensive and reproducible analysis of the complex and voluminous metabolomics data produced by the profiling approach. Time- and concentration-dependent responses were clearly evident in the metabolomic profiles. To obtain a more comprehensive picture of the mode of action, transcriptomics and proteomics data were also integrated. For toxicity profiling of chloroacetaldehyde, 428 and 317 metabolite features were detectable in positive and negative modes, respectively, after stringent removal of chemical noise and unstable signals. Changes upon treatment were explored using principal component analysis, and statistically significant differences were identified using linear models for microarray assays. The analysis revealed toxic effects only for the treatment with 35 μmol·liter(-1) for 3 and 14 days. The most regulated metabolites were glutathione and metabolites related to the oxidative stress response of the cells. These findings are corroborated by proteomics and transcriptomics data, which show, among other things, an activation of the Nrf2 and ATF4 pathways. PMID:26055719

  8. 1H NMR-based lipidomics of rodent fur: species-specific lipid profiles and SCD1 inhibitor-related dermal toxicity[S

    PubMed Central

    Khandelwal, Purnima; Stryker, Steven; Chao, Hannguang; Aranibar, Nelly; Lawrence, R. Michael; Madireddi, Malavi; Zhao, Wenjun; Chen, Luping; Reily, Michael D.

    2014-01-01

    A method is described that allows noninvasive identification and quantitative assessment of lipid classes present in sebaceous excretions in rodents. The method relies on direct high-field proton NMR analysis of common group lipid protons in deuterated organic solvent extracts of fur. Extracts from as little as 15 mg of fur from rat, mouse, and hamster provided acceptable results on a 600 MHz NMR equipped with a cryogenically cooled proton-observe probe. In rats, sex- and age-related differences in lipid composition are larger than differences in fur collected from various body regions within an individual and much larger than interanimal differences in age- and sex-matched specimens. The utility of this method to noninvasively monitor drug-induced sebaceous gland atrophy in rodents is demonstrated in rats dosed with a stearoyl-CoA desaturase 1 (SCD1) inhibitor. In this model, a 35% reduction in sebum lipids, extracted from fur, was observed. Finally, structural elucidation of cholesta-7,24-dien-3β-ol ester as the most prominent, previously unidentified sebum sterol ester in male Syrian hamsters is described. The utility of this method for drug and cosmetic safety and efficacy assessment is discussed. PMID:24755647

  9. Toxicity of nickel ions and comprehensive analysis of nickel ion-associated gene expression profiles in THP-1 cells

    PubMed Central

    ZHANG, YING; ZHANG, ZHI-WEI; XIE, YU-MEI; WANG, SHU-SHUI; QIU, QING-HUAN; ZHOU, YING-LING; ZENG, GUO-HONG

    2015-01-01

    The aim of the present study was to explore the toxic effects and underlying mechanisms of nickel ions during therapeutic nickel-based alloy-treatment in congenital heart disease by investigating the metal-induced cytotoxicity to the human monocyte-derived macrophage cell line THP-1. THP-1 cells were treated with NiCl2·6H2O (25, 50, 100, 200, 400 and 800 µM) for 24, 48 and 72 h, respectively. MTT was applied to detect THP-1 cell proliferation following NiCl2 treatment. Apoptosis of THP-1 cells was quantified using flow cytometry. Illumina sequencing was used for screening the associated genes, whose mRNA expression levels were further confirmed by quantitative real-time polymerase chain reaction. High concentrations of nickel ions had a significant suppressive effect on cell proliferation at the three concentrations investigated (200, 400 and 800 µM). Treatment with nickel ions (25–400 µM) for 48 h reduced cell viability in a dose-dependent manner. The mRNA expression levels of RELB, FIGF, SPI-1, CXCL16 and CRLF2 were significantly increased following nickel treatment. The results of the present study suggested that nickel ions exert toxic effects on THP-1 cell growth, which may indicate toxicity of the nickel ion during treatment of congenital heart disease. The identification of genes modified by the toxic effects of nickel on THP-1 cells (EPOR, RELB, FIGF, SPI-1, TGF-β1, CXCL16 and CRLF2) may aid in the development of interventional measures for the treatment/prevention of nickel ion-associated toxic effects during the treatment of congenital heart disease. PMID:26044615

  10. Subchronic oral toxicity and metabolite profiling of the p53 stabilizing agent, CP-31398, in rats and dogs.

    PubMed

    Johnson, William D; Muzzio, Miguel; Detrisac, Carol J; Kapetanovic, Izet M; Kopelovich, Levy; McCormick, David L

    2011-11-18

    CP-31398 (N'-[2-[2-(4-methoxyphenyl)ethenyl]-4-quinazolinyl]-N,N-dimethyl-1,3-propanediamine dihydrochloride) is a styrylquinazoline that stabilizes the DNA binding conformation of p53, thereby maintaining the activity of p53 as a transcription factor and tumor suppressor. In consideration of the potential use of p53 stabilizers for cancer prevention and therapy, 28-day studies (with recovery) were performed to characterize the toxicity of CP-31398 in rats and dogs. In the rat study, groups of 15 CD rats/sex received daily gavage exposure to CP-31398 at 0, 40, 80, or 160mg/kg/day (0, 240, 480, or 960mg/m(2)/day). In the dog study, groups of five beagle dogs received daily gavage exposure to CP-31398 at 0, 10, 20, or 40mg/kg/day (0, 200, 400, or 800mg/m(2)/day). The high dose of CP-31398 induced mortality in both species: seven male rats and four female rats died as a result of hepatic infarcts, and two female dogs died as a result of hepatic necrosis without evidence of thrombosis. No deaths were seen in the mid- or low-dose groups in either species. In dogs, sporadic emesis was seen in the high dose and mid dose groups, and reductions in body weight gain were observed in all drug-exposed groups. CP-31398 induced mild anemia in both species; clinical pathology data also demonstrated hepatic toxicity, renal toxicity, inflammatory reactions, and coagulopathies in rats in the high dose and mid dose groups. Treatment-related microscopic changes in high dose and mid dose rats were identified in the liver, kidney, heart, bone marrow, lung, adrenals, spleen, thymus, skeletal muscle, and ovary; microscopic changes in the liver, heart, lung, and adrenals persisted through the recovery period. In dogs, microscopic changes were identified in the central nervous system, lung, and liver; changes in all tissues remained at the end of the recovery period. The liver is the primary site of limiting toxicity for CP-31398 in rats, and is also a key site of toxicity in dogs. The

  11. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    SciTech Connect

    Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; Ende, Piet van den; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.

    2012-02-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  12. Combination therapies with oxaliplatin and oral capecitabine or intravenous 5-FU show similar toxicity profiles in gastrointestinal carcinoma patients if hand-food syndrome prophylaxis is performed continuously

    PubMed Central

    WEHLER, THOMAS C.; CAO, YANG; GALLE, PETER R.; THEOBALD, MATTHIAS; MOEHLER, MARKUS; SCHIMANSKI, CARL C.

    2012-01-01

    The use of anticancer drugs in palliative settings is often limited by their severe toxic effects. In gastrointestinal carcinomas the 5-fluorouracil-based palliative regimen FOLFOX-4 is often preferred to the equally effective, but more convenient oral capecitabine-based regimen XELOX. This preference is mainly based on the fact that the highly effective oral agent capecitabine induces hand-foot syndrome (HFS). In this study, we investigated whether the continuous administration of skin prophylaxis (10% urea, panthenol, bisabolol, vitamin A, C and E) is capable of protecting against capecitabine-induced HFS and allowing a more convenient oral therapeutic option. In this retrospective analysis, the toxicity profiles, according to NCI CTCAE 3.0 criteria, of 54 patients with gastrointestinal cancer who received either XELOX (34 patients) or FOLFOX-4 (20 patients) were compared using Fisher tests. The treatment protocols that were compared, herein, did not differ significantly in the majority of the analyzed items, with the exception of increased nausea (XELOX-70), fatigue (XELOX-130) and tumor pain (XELOX-70 and XELOX-130). No significant differences were observed among the various groups with regard to emesis, diarrhea, mucositis, exanthema, alopecia, loss of weight and the incidence of infections. In particular, no significant differences in toxicity levels occurred in terms of dose, and HFS was limited if skin prophylaxis was performed continuously. XELOX-based palliative regimens provide an equally effective and comparably toxic therapeutic alternative to FOLFOX-4 if HFS prophylaxis is performed continuously. Since the oral administration of capecitabine is a more convenient method of application, it provides patients with a quality of life-preserving therapeutic alternative. PMID:22783416

  13. Combination therapies with oxaliplatin and oral capecitabine or intravenous 5-FU show similar toxicity profiles in gastrointestinal carcinoma patients if hand-food syndrome prophylaxis is performed continuously.

    PubMed

    Wehler, Thomas C; Cao, Yang; Galle, Peter R; Theobald, Matthias; Moehler, Markus; Schimanski, Carl C

    2012-06-01

    The use of anticancer drugs in palliative settings is often limited by their severe toxic effects. In gastrointestinal carcinomas the 5-fluorouracil-based palliative regimen FOLFOX-4 is often preferred to the equally effective, but more convenient oral capecitabine-based regimen XELOX. This preference is mainly based on the fact that the highly effective oral agent capecitabine induces hand-foot syndrome (HFS). In this study, we investigated whether the continuous administration of skin prophylaxis (10% urea, panthenol, bisabolol, vitamin A, C and E) is capable of protecting against capecitabine-induced HFS and allowing a more convenient oral therapeutic option. In this retrospective analysis, the toxicity profiles, according to NCI CTCAE 3.0 criteria, of 54 patients with gastrointestinal cancer who received either XELOX (34 patients) or FOLFOX-4 (20 patients) were compared using Fisher tests. The treatment protocols that were compared, herein, did not differ significantly in the majority of the analyzed items, with the exception of increased nausea (XELOX-70), fatigue (XELOX-130) and tumor pain (XELOX-70 and XELOX-130). No significant differences were observed among the various groups with regard to emesis, diarrhea, mucositis, exanthema, alopecia, loss of weight and the incidence of infections. In particular, no significant differences in toxicity levels occurred in terms of dose, and HFS was limited if skin prophylaxis was performed continuously. XELOX-based palliative regimens provide an equally effective and comparably toxic therapeutic alternative to FOLFOX-4 if HFS prophylaxis is performed continuously. Since the oral administration of capecitabine is a more convenient method of application, it provides patients with a quality of life-preserving therapeutic alternative. PMID:22783416

  14. Vertical profile, source apportionment, and toxicity of PAHs in sediment cores of a wharf near the coal-based steel refining industrial zone in Kaohsiung, Taiwan.

    PubMed

    Chen, Chih-Feng; Chen, Chiu-Wen; Ju, Yun-Ru; Dong, Cheng-Di

    2016-03-01

    Three sediment cores were collected from a wharf near a coal-based steel refining industrial zone in Kaohsiung, Taiwan. Analyses for 16 polycyclic aromatic hydrocarbons (PAHs) of the US Environmental Protection Agency priority list in the core sediment samples were conducted using gas chromatography-mass spectrometry. The vertical profiles of PAHs in the core sediments were assessed, possible sources and apportionment were identified, and the toxicity risk of the core sediments was determined. The results from the sediment analyses showed that total concentrations of the 16 PAHs varied from 11774 ± 4244 to 16755 ± 4593 ng/g dry weight (dw). Generally, the vertical profiles of the PAHs in the sediment cores exhibited a decreasing trend from the top to the lower levels of the S1 core and an increasing trend of PAHs from the top to the lower levels of the S2 and S3 cores. Among the core sediment samples, the five- and six-ring PAHs were predominantly in the S1 core, ranging from 42 to 54 %, whereas the composition of the PAHs in the S2 and S3 cores were distributed equally across three groups: two- and three-ring, four-ring, and five- and six-ring PAHs. The results indicated that PAH contamination at the site of the S1 core had a different source. The molecular indices and principal component analyses with multivariate linear regression were used to determine the source contributions, with the results showing that the contributions of coal, oil-related, and vehicle sources were 38.6, 35.9, and 25.5 %, respectively. A PAH toxicity assessment using the mean effect range-median quotient (m-ERM-q, 0.59-0.79), benzo[a]pyrene toxicity equivalent (TEQ(carc), 1466-1954 ng TEQ/g dw), and dioxin toxicity equivalent (TEQ(fish), 3036-4174 pg TEQ/g dw) identified the wharf as the most affected area. The results can be used for regular monitoring, and future pollution prevention and management should target the coal-based industries in this region for pollution reduction

  15. A comparison of toxicity profiles between the lower and standard dose capecitabine in breast cancer: a systematic review and meta-analysis.

    PubMed

    Nishijima, Tomohiro F; Suzuki, Maya; Muss, Hyman B

    2016-04-01

    Capecitabine 1000 mg/m(2) bid × 14 days every 21 days (14/21) has been reported to have similar efficacy but more favorable toxicity profile than the approved dosage of 1250 mg/m(2). However, a dose-toxicity relationship of capecitabine in breast cancer patients has not been fully elucidated. We performed a systematic review and meta-analysis to compare a safety profile between capecitabine starting dose of 1000 and 1250 mg/m(2) bid. Studies were identified using PubMed, ASCO, and San Antonio Breast Cancer Symposium abstract databases through December 2015. Eligible trials included phase II/III trials of capecitabine monotherapy at 1000 or 1250 mg/m(2) bid (14/21) for breast cancer patients that reported adequate safety data for all (grade 1-4) or high (grade 3-4) grade hand foot syndrome (HFS), diarrhea, fatigue, nausea, vomiting, stomatitis, neutropenia, thrombocytopenia, or anemia, as well as dose reductions, treatment discontinuation or treatment-related deaths. The summary incidence was calculated using random-effects models. A total of 4833 patients from 34 trials were included. 1218 and 3615 patients were treated with capecitabine 1000 and 1250 mg/m(2) bid, respectively. A significantly lower incidence of dose reduction (15.9 vs. 39.0 %; P = 0.007), high-grade HFS (12.0 vs. 19.0 %; P = 0.01), diarrhea (5.3 vs. 9.1 %; P = 0.01), and neutropenia (1.8 vs. 7.3 %; P < 0.01), and all-grade neutropenia (5.8 vs. 25.4 %; P = 0.01) was seen in capecitabine 1000 mg/m(2) compared to 1250 mg/m(2). Capecitabine monotherapy at 1000 mg/m(2) bid (14/21) has a clinically meaningful and significantly better toxicity profile compared to 1250 mg/m(2) bid (14/21). PMID:26988358

  16. Toxicity profiling of water contextual zinc oxide, silver, and titanium dioxide nanoparticles in human oral and gastrointestinal cell systems.

    PubMed

    Giovanni, Marcella; Tay, Chor Yong; Setyawati, Magdiel Inggrid; Xie, Jianping; Ong, Choon Nam; Fan, Rongli; Yue, Junqi; Zhang, Lifeng; Leong, David Tai

    2015-12-01

    Engineered nanoparticles (ENPs) are increasingly detected in water supply due to environmental release of ENPs as the by-products contained within the effluent of domestic and industrial run-off. The partial recycling of water laden with ENPs, albeit at ultra-low concentrations, may pose an uncharacterized threat to human health. In this study, we investigated the toxicity of three prevalent ENPs: zinc oxide, silver, and titanium dioxide over a wide range of concentrations that encompasses drinking water-relevant concentrations, to cellular systems representing oral and gastrointestinal tissues. Based on published in silico-predicted water-relevant ENPs concentration range from 100 pg/L to 100 µg/L, we detected no cytotoxicity to all the cellular systems. Significant cytotoxicity due to the NPs set in around 100 mg/L with decreasing extent of toxicity from zinc oxide to silver to titanium dioxide NPs. We also found that noncytotoxic zinc oxide NPs level of 10 mg/L could elevate the intracellular oxidative stress. The threshold concentrations of NPs that induced cytotoxic effect are at least two to five orders of magnitude higher than the permissible concentrations of the respective metals and metal oxides in drinking water. Based on these findings, the current estimated levels of NPs in potable water pose little cytotoxic threat to the human oral and gastrointestinal systems within our experimental boundaries. PMID:24930694

  17. In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components

    SciTech Connect

    Verma, Ranjana; Xu, Xiufen; Jaiswal, Manoj K.; Olsen, Cara; Mears, David; Caretti, Giuseppina; Galdzicki, Zygmunt

    2011-06-15

    Tungsten-alloy has carcinogenic potential as demonstrated by cancer development in rats with intramuscular implanted tungsten-alloy pellets. This suggests a potential involvement of epigenetic events previously implicated as environmental triggers of cancer. Here, we tested metal induced cytotoxicity and epigenetic modifications including H3 acetylation, H3-Ser10 phosphorylation and H3-K4 trimethylation. We exposed human embryonic kidney (HEK293), human neuroepithelioma (SKNMC), and mouse myoblast (C2C12) cultures for 1-day and hippocampal primary neuronal cultures for 1-week to 50-200 {mu}g/ml of tungsten-alloy (91% tungsten/6% nickel/3% cobalt), tungsten, nickel, and cobalt. We also examined the potential role of intracellular calcium in metal mediated histone modifications by addition of calcium channel blockers/chelators to the metal solutions. Tungsten and its alloy showed cytotoxicity at concentrations > 50 {mu}g/ml, while we found significant toxicity with cobalt and nickel for most tested concentrations. Diverse cell-specific toxic effects were observed, with C2C12 being relatively resistant to tungsten-alloy mediated toxic impact. Tungsten-alloy, but not tungsten, caused almost complete dephosphorylation of H3-Ser10 in C2C12 and hippocampal primary neuronal cultures with H3-hypoacetylation in C2C12. Dramatic H3-Ser10 dephosphorylation was found in all cobalt treated cultures with a decrease in H3 pan-acetylation in C2C12, SKNMC and HEK293. Trimethylation of H3-K4 was not affected. Both tungsten-alloy and cobalt mediated H3-Ser10 dephosphorylation were reversed with BAPTA-AM, highlighting the role of intracellular calcium, confirmed with 2-photon calcium imaging. In summary, our results for the first time reveal epigenetic modifications triggered by tungsten-alloy exposure in C2C12 and hippocampal primary neuronal cultures suggesting the underlying synergistic effects of tungsten, nickel and cobalt mediated by changes in intracellular calcium homeostasis

  18. Building America Top Innovations 2014 Profile: ASHRAE Standard 62.2. Ventilation and Acceptable Indoor Air Quality in Low-Rise Residential Buildings

    SciTech Connect

    none,

    2014-11-01

    This 2014 Top Innovations profile describes Building America research and support in developing and gaining adoption of ASHRAE 62.2, a residential ventilation standard that is critical to transforming the U.S. housing industry to high-performance homes.

  19. Transcript and protein profiling analysis of OTA-induced cell death reveals the regulation of the toxicity response process in Arabidopsis thaliana

    PubMed Central

    Wang, Yan; Peng, Xiaoli; Xu, Wentao; Luo, YunBo; Zhao, Weiwei; Hao, Junran; Liang, Zhihong; Zhang, Yu; Huang, Kunlun

    2012-01-01

    Ochratoxin A (OTA) is a toxic isocoumarin derivative produced by various species of mould which mainly grow on grain, coffee, and nuts. Recent studies have suggested that OTA induces cell death in plants. To investigate possible mechanisms of OTA phytotoxicity, both digital gene expression (DGE) transcriptomic and two-dimensional electrophoresis proteomic analyses were used, through which 3118 genes and 23 proteins were identified as being up- or down-regulated at least 2-fold in Arabidopsis leaf in response to OTA treatment. First, exposure of excised Arabidopsis thaliana leaves to OTA rapidly causes the hypersensitive reponse, significantly accelerates the increase of reactive oxygen species and malondialdehyde, and enhances antioxidant enzyme defence responses and xenobiotic detoxification. Secondly, OTA stimulation causes dynamic changes in transcription factors and activates the membrane transport system dramatically. Thirdly, a concomitant persistence of compromised photosynthesis and photorespiration is indicative of a metabolic shift from a highly active to a weak state. Finally, the data revealed that ethylene, salicylic acid, jasmonic acid, and mitogen-activated protein kinase signalling molecules mediate the process of toxicity caused by OTA. Profiling analyses on Arabidopsis in response to OTA will provide new insights into signalling transduction that modulates the OTA phytotoxicity mechanism, facilitate mapping of regulatory networks, and extend the ability to improve OTA tolerance in Arabidopsis. PMID:22207617

  20. Transcript and protein profiling analysis of OTA-induced cell death reveals the regulation of the toxicity response process in Arabidopsis thaliana.

    PubMed

    Wang, Yan; Peng, Xiaoli; Xu, Wentao; Luo, Yunbo; Zhao, Weiwei; Hao, Junran; Liang, Zhihong; Zhang, Yu; Huang, Kunlun

    2012-03-01

    Ochratoxin A (OTA) is a toxic isocoumarin derivative produced by various species of mould which mainly grow on grain, coffee, and nuts. Recent studies have suggested that OTA induces cell death in plants. To investigate possible mechanisms of OTA phytotoxicity, both digital gene expression (DGE) transcriptomic and two-dimensional electrophoresis proteomic analyses were used, through which 3118 genes and 23 proteins were identified as being up- or down-regulated at least 2-fold in Arabidopsis leaf in response to OTA treatment. First, exposure of excised Arabidopsis thaliana leaves to OTA rapidly causes the hypersensitive reponse, significantly accelerates the increase of reactive oxygen species and malondialdehyde, and enhances antioxidant enzyme defence responses and xenobiotic detoxification. Secondly, OTA stimulation causes dynamic changes in transcription factors and activates the membrane transport system dramatically. Thirdly, a concomitant persistence of compromised photosynthesis and photorespiration is indicative of a metabolic shift from a highly active to a weak state. Finally, the data revealed that ethylene, salicylic acid, jasmonic acid, and mitogen-activated protein kinase signalling molecules mediate the process of toxicity caused by OTA. Profiling analyses on Arabidopsis in response to OTA will provide new insights into signalling transduction that modulates the OTA phytotoxicity mechanism, facilitate mapping of regulatory networks, and extend the ability to improve OTA tolerance in Arabidopsis. PMID:22207617

  1. Discriminating the molecular basis of hepatotoxicity using the large-scale characteristic molecular signatures of toxicants by expression profiling analysis.

    PubMed

    Eun, Jung Woo; Ryu, So Yeon; Noh, Ji Heon; Lee, Min-Jae; Jang, Ja-Jun; Ryu, Jae Chun; Jung, Kwang Hwa; Kim, Jeong Kyu; Bae, Hyun Jin; Xie, Hongjian; Kim, Su Young; Lee, Sug Hyung; Park, Won Sang; Yoo, Nam Jin; Lee, Jung Young; Nam, Suk Woo

    2008-07-30

    Predicting the potential human health risk posed by chemical stressors has long been a major challenge for toxicologists, and the use of microarrays to measure responses to toxicologically relevant genes, and to identify selective, sensitive biomarkers of toxicity is a major application of predictive and discovery toxicology. To investigate this possibility, we investigated whether carcinogens (at doses known to induce liver tumors in chronic exposure bioassays) deregulate characteristic sets of genes in mice. Male C3H/He mice were dosed with two hepatocarcinogens (vinyl chloride (VC, 50-25 mg/kg), aldrin (AD, 0.8-0.4 mg/kg)), or two non-hepatocarcinogens (copper sulfate (CS, 150-60 mg/kg), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T, 150-60 mg/kg)). Large-scale molecular changes elicited by these four hepatotoxicants in liver tissues were analyzed using DNA microarray. Three days after administration, no significant phenotypic changes were induced by these four different hepatotoxicants in terms of histological examination or blood biochemical assay. However, unsupervised hierarchical analysis of gene expressional changes induced by hepatotoxicants resulted in two major gene subclusters on dendrogram, i.e., a carcinogen (VN, AD) and non-carcinogen group (CS, 2,4,5-T), and also revealed that distinct molecular signatures exist. These signatures were founded on well-defined functional gene categories and may differentiate genotoxic and non-genotoxic carcinogens. Furthermore, Venn diagram analysis allowed us to identify carcinogen and non-carcinogen-associated molecular signatures. Using statistical methods, we analyzed outlier genes for four different classes (genotoxic-, non-genotoxic-carcinogen, genotoxic-, non-genotoxic non-carcinogen) in terms of their potential to predict different modes-of-action. In conclusion, the identification of large-scale molecular changes in different hepatocarcinogen exposure models revealed that different types of hepatotoxicants are

  2. Metal toxicity inferred from algal population density, heterotrophic substrate use, and fatty acid profile in a small stream

    SciTech Connect

    Genter, R.B.; Lehman, R.M.

    2000-04-01

    The purpose of this study was to examine relations between metal concentrations in periphyton and the abundance of algal species, heterotrophic use of 95 carbon sources, and phospholipid fatty acids (PLFA) of the periphyton in a small stream spanning a mine in Lemhi County, Idaho, USA. Two upstream two mine, and two downstream sites were examined. Elevated concentrations of As and Cu at the mine sites were associated with communities that were depleted of diatoms and filamentous blue-green algae and characterized by a low-diversity community dominated by a single blue-green alga and patchy populations of the diatom Achnanthidium minutissimum and a filamentous green alga. Carbon source use and PLFA profiles provided a rapid assessment of stream conditions that were consistent with algal taxonomy and with the hypotheses constructed from previous reports on periphyton responses to metal stress.

  3. 454 pyrosequencing-based analysis of gene expression profiles in the amphipod Melita plumulosa: transcriptome assembly and toxicant induced changes.

    PubMed

    Hook, Sharon E; Twine, Natalie A; Simpson, Stuart L; Spadaro, David A; Moncuquet, Philippe; Wilkins, Marc R

    2014-08-01

    Next generation sequencing using Roche's 454 pyrosequencing platform can be used to generate genomic information for non-model organisms, although there are bioinformatic challenges associated with these studies. These challenges are compounded by a lack of a standardized protocol to either assemble data or to evaluate the quality of a de novo transcriptome. This study presents an assembly of the control and toxicant responsive transcriptome of Melita plumulosa, an Australian amphipod commonly used in ecotoxicological studies. RNA was harvested from control amphipods, juvenile amphipods, and from amphipods exposed to either metal or diesel contaminated sediments. This RNA was used as the basis for a 454 based transcriptome sequencing effort. Sequencing generated 1.3 million reads from control, juvenile, metal-exposed and diesel-exposed amphipods. Different read filtering and assembly protocols were evaluated to generate an assembly that (i) had an optimal number of contigs; (ii) had long contigs; (iii) contained a suitable representation of conserved genes; and (iv) had long ortholog alignment lengths relative to the length of each contig. A final assembly, generated using fixed-length trimming based on the sequence quality scores, followed by assembly using the MIRA algorithm, produced the best results. The 26,625 contigs generated via this approach were annotated using Blast2GO, and the differential expression between treatments and control was determined by mapping with BWA followed by DESeq. Although the mapping generated low coverage, many differentially expressed contigs, including some with known developmental or toxicological function, were identified. This study demonstrated that 454 pyrosequencing is an effective means of generating reference transcriptome information for organisms, such as the amphipod M. plumulosa, that have no genomic information available in databases or in closely related sequenced species. It also demonstrated how optimization of

  4. Acceptance speech.

    PubMed

    Carpenter, M

    1994-01-01

    In Bangladesh, the assistant administrator of USAID gave an acceptance speech at an awards ceremony on the occasion of the 25th anniversary of oral rehydration solution (ORS). The ceremony celebrated the key role of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) in the discovery of ORS. Its research activities over the last 25 years have brought ORS to every village in the world, preventing more than a million deaths each year. ORS is the most important medical advance of the 20th century. It is affordable and client-oriented, a true appropriate technology. USAID has provided more than US$ 40 million to ICDDR,B for diarrheal disease and measles research, urban and rural applied family planning and maternal and child health research, and vaccine development. ICDDR,B began as the relatively small Cholera Research Laboratory and has grown into an acclaimed international center for health, family planning, and population research. It leads the world in diarrheal disease research. ICDDR,B is the leading center for applied health research in South Asia. It trains public health specialists from around the world. The government of Bangladesh and the international donor community have actively joined in support of ICDDR,B. The government applies the results of ICDDR,B research to its programs to improve the health and well-being of Bangladeshis. ICDDR,B now also studies acute respiratory diseases and measles. Population and health comprise 1 of USAID's 4 strategic priorities, the others being economic growth, environment, and democracy, USAID promotes people's participation in these 4 areas and in the design and implementation of development projects. USAID is committed to the use and improvement of ORS and to complementary strategies that further reduce diarrhea-related deaths. Continued collaboration with a strong user perspective and integrated services will lead to sustainable development. PMID:12345470

  5. Acceptance speech.

    PubMed

    Yusuf, C K

    1994-01-01

    I am proud and honored to accept this award on behalf of the Government of Bangladesh, and the millions of Bangladeshi children saved by oral rehydration solution. The Government of Bangladesh is grateful for this recognition of its commitment to international health and population research and cost-effective health care for all. The Government of Bangladesh has already made remarkable strides forward in the health and population sector, and this was recognized in UNICEF's 1993 "State of the World's Children". The national contraceptive prevalence rate, at 40%, is higher than that of many developed countries. It is appropriate that Bangladesh, where ORS was discovered, has the largest ORS production capacity in the world. It was remarkable that after the devastating cyclone in 1991, the country was able to produce enough ORS to meet the needs and remain self-sufficient. Similarly, Bangladesh has one of the most effective, flexible and efficient control of diarrheal disease and epidemic response program in the world. Through the country, doctors have been trained in diarrheal disease management, and stores of ORS are maintained ready for any outbreak. Despite grim predictions after the 1991 cyclone and the 1993 floods, relatively few people died from diarrheal disease. This is indicative of the strength of the national program. I want to take this opportunity to acknowledge the contribution of ICDDR, B and the important role it plays in supporting the Government's efforts in the health and population sector. The partnership between the Government of Bangladesh and ICDDR, B has already borne great fruit, and I hope and believe that it will continue to do so for many years in the future. Thank you. PMID:12345479

  6. Nanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats

    PubMed Central

    Zhang, Cong; Peng, Fan; Liu, Wei; Wan, Jiangling; Wan, Chunxi; Xu, Huibi; Lam, Christopher Waikei; Yang, Xiangliang

    2014-01-01

    After oral administration in rodents, triptolide (TP), a diterpenoid triepoxide compound, active as anti-inflammatory, immunosuppressive, anti-fertility, anti-cystogenesis, and anticancer agent, is rapidly absorbed into the blood circulation (from 5.0 to 19.5 minutes after dosing, depending on the rodent species) followed by a short elimination half-life (from about 20 minutes to less than 1 hour). Such significant and rapid fluctuations of TP in plasma likely contribute to its toxicity, which is characterized by injury to hepatic, renal, digestive, reproductive, and hematological systems. With the aim of prolonging drug release and improving its safety, TP-loaded nanostructured lipid carriers (TP-NLCs), composed of Compritol® 888 ATO (solid lipid) and Capryol™ 90 (liquid lipid), were developed using a microemulsion technique. The formulated TP-NLCs were also characterized and in vitro release was evaluated using the dialysis bag diffusion technique. In addition, the pharmacokinetics and toxicology profiles of TP-NLCs were compared to free TP and TP-loaded solid lipid nanoparticles (TP-SLNs; containing Compritol 888 ATO only). Results demonstrate that TP-NLCs had mean particle size of 231.8 nm, increased drug encapsulation with a 71.6% efficiency, and stable drug incorporation for over 1-month. TP-NLCs manifested a better in vitro sustained-release pattern compared to TP-SLNs. Furthermore, TP-NLCs prolonged mean residence time (MRT)0–t (P<0.001, P<0.001), delayed Tmax (P<0.01, P<0.05) and decreased Cmax (P<0.01, P<0.05) compared to free TP and TP-SLNs, respectively, which was associated with reduced subacute toxicity in male rats. In conclusion, our data suggest that TP-NLCs are superior to TP-SLNs and could be a promising oral delivery system for a safer use of TP. PMID:24591827

  7. Toxicity Profile and Pharmacokinetic Study of A Phase I Low-Dose Schedule-Dependent Radiosensitizing Paclitaxel Chemoradiation Regimen for Inoperable Non-Small-Cell Lung Cancer

    SciTech Connect

    Chen, Yuhchyau Pandya, Kishan J.; Feins, Richard; Johnstone, David W.; Watson, Thomas; Smudzin, Therese; Keng, Peter C.

    2008-06-01

    Purpose: We report the toxicity profile and pharmacokinetic data of a schedule-dependent chemoradiation regimen using pulsed low-dose paclitaxel for radiosensitization in a Phase I study for inoperable non-small-cell lung cancer. Methods and Materials: Paclitaxel at escalating doses of 15 mg/m{sup 2}, 20 mg/m{sup 2}, and 25 mg/m{sup 2} were infused on Monday, Wednesday, and Friday with daily chest radiation in cohorts of 6 patients. Daily radiation was delayed for maximal G2/M arrest and apoptotic effect, an observation from preclinical investigations. Plasma paclitaxel concentration was determined by high-performance liquid chromatography. Results: Dose-limiting toxicities included 3 of 18 patients with Grade 3 pneumonitis and 3 of 18 patients with Grade 3 esophagitis. There was no Grade 4 or 5 pneumonitis or esophagitis. There was also no Grade 3 or 4 neutropenia, thrombocytopenia, anemia or neuropathy. For Dose Levels I (15 mg/m{sup 2}), II (20 mg/m{sup 2}), and III (25 mg/m{sup 2}), the mean peak plasma level was 0.23 {+-} 0.06 {mu}mol/l, 0.32 {+-} 0.05 {mu}mol/l, and 0.52 {+-} 0.14 {mu}mol/l, respectively; AUC was 0.44 {+-} 0.09 {mu}mol/l, 0.61 {+-} 0.1 {mu}mol/l, and 0.96 {+-} 0.23 {mu}mol/l, respectively; and duration of drug concentration >0.05 {mu}mol/l (t > 0.05 {mu}mol/l) was 1.6 {+-} 0.3 h, 1.9 {+-} 0.2 h, and 3.0 {+-} 0.9 h, respectively. Conclusion: Pulsed low-dose paclitaxel chemoradiation is associated with low toxicity. Pharmacokinetic data showed that plasma paclitaxel concentration >0.05 {mu}mol/l for a minimum of 1.6 h was sufficient for effective radiosensitization.

  8. Accumulation and depuration profiles of PSP toxins in the short-necked clam Tapes japonica fed with the toxic dinoflagellate Alexandrium catenella.

    PubMed

    Samsur, Mohamad; Yamaguchi, Yasunaga; Sagara, Takefumi; Takatani, Tomohiro; Arakawa, Osamu; Noguchi, Tamao

    2006-09-01

    A toxic dinoflagellate responsible for paralytic shellfish poisoning (PSP), Alexandrium catenella (Ac) was fed to the short-necked clam Tapes japonica, and the accumulation and depuration profiles of PSP toxins were investigated by means of high-performance liquid chromatography with postcolumn fluorescence derivatization (HPLC-FLD). The short-necked clams ingested more than 99% of the Ac cells (4 x 10(7)cells) supplied once at the beginning of experiment, and accumulated a maximal amount of toxin (185 nmol/10 clams) after 12h. The rate of toxin accumulation at that time was 23%, which rapidly decreased thereafter. Composition of the PSP toxin accumulated in the clams obviously different from that of Ac even 0.5h after the cell supply, the proportion of C1+2 being much higher than in Ac, although the reason remains to be elucidated. In contrast, a higher ratio of gonyautoxin (GTX)1+4 than in Ac was detected in the toxin profiles of clam excrements. The variation in toxin composition derived presumably from the transformation of toxin analogues in clams was observed from 0.5h, such as reversal of the ratio of C1 to C2, and appearance of carbamate (saxitoxin (STX), neoSTX and GTX2, 3) and decarbamoyl (dc) derivatives (dcSTX and dcGTX2, 3), which were undetectable in Ac cells. The total amount of toxin distributed over Ac cells, clams and their excrements gradually declined, and only 1% of supplied toxin was detected at the end of experiment. PMID:16887162

  9. Phenological and liver antioxidant profiles of adult Nile tilapia (Oreochromis niloticus) exposed to toxic live cyanobacterium (Microcystis aeruginosa Kützing) cells.

    PubMed

    Khairy, Hanan M; Ibrahim, Marwa A; Ibrahem, Mai D

    2012-01-01

    Blue-green algae (cyanobacteria) constitute the greater part of the phytoplankton. Microcystis aeruginosa is amongst the most ubiquitously distributed cyanobacterial species, and almost invariably produces cyclic heptapeptide toxins called microcystins (MCs). The present study was designed to investigate the phenological and liver antioxidant profiles of the Nile tilapia Oreochromis niloticus chronically exposed to toxic live M. aeruginosa cells. Fish were grown in the absence and presence of M. aeruginosa in three different concentrations for seven days, and subsequently reared for another 30 days in the absence of the cyanobacteria. While cyanobacteria did not cause any fish mortality, there was a progressive development of yellowish discolouration in the livers of exposed fish. In the livers, the activities and levels of superoxide dismutase (SOD), lactate dehydrogenase (LDH), glutathione (GSH), and lipid peroxidation products like malondialdehyde (MDA) were elevated in response to the concentration of M. aeruginosa. Moreover, DNA fragmentation and DNA-protein crosslinks were measured. These parameters can thus be considered potential biomarkers for the fish exposure to M. aeruginosa. The present study sheds light on cyanobacterial blooms like health, environmental, and economic problem, respectively. PMID:23413757

  10. Toxic action/toxicity.

    PubMed

    Hathway, D E

    2000-02-01

    Some six or so physiological systems, essential to normal mammalian life, are involved in poisoning; an intoxication that causes severe injury to any one of them could be life threatening. Reversible chemical reactions showing Scatchard-type binding are exemplified by CO, CN- and cyclodiene neurotoxin insecticide intoxications, and by antigen-antibody complex formation. Haemoglobin (Hb) molecular biology accounts for the allosteric co-operativity and other characteristics of CO poisoning, CN- acts as a powerful cytochrome oxidase inhibitor, and antigen binding in a deep antibody cleft between two domains equipped with epitopes for antigen-binding groups explains hapten-specific immune reactions. Covalent chemical reactions with second-order (SN2) kinetics characterize Hg and Cd poisonings, the reactions of organophosphates and phosphonates with acetylcholinesterase and neurotoxic esterase and the reaction sequence whereby Paraquat accepts electrons and generates superoxide under aerobic conditions. Indirect carcinogens require cytochrome P450 activation to form DNA adducts in target-organ DNA and cause cancer, but a battery of detoxifying enzymes clustered with the P450 system must be overcome. Thus, S-metabolism competes ineffectively with target DNA for reactive vinyl chloride (VC) metabolites, epoxide hydrolase is important to the metabolism and carcinogenicity of alfatoxins and polycyclic aromatic hydrocarbons (benzo[a]pyrene, etc.), and the non-toxic 2-naphthylhydroxylamine N-glucuronide acts as a transport form in 2-naphthylamine bladder cancer. VC liver-cancer pathogenesis is explicable in terms of the presence of the glutathione S-transferase detoxifying system in hepatocytes and its absence from the fibroblastic elements, and of the VC concentrations reaching the liver by different administrative routes. In VC carcinogenicity, chemical reactions give imidazo-cyclization products with nucleoside residues of target DNA, and in benzene leukaemia, Z

  11. Toxic substances alert program

    NASA Technical Reports Server (NTRS)

    Junod, T. L.

    1978-01-01

    A toxicity profile is provided, of 187 toxic substances procured by NASA Lewis Research Center during a 3 1/2 year period, including 27 known or suspected carcinogens. The goal of the program is to assure that the center's health and safety personnel are aware of the procurement and use of toxic substances and to alert and inform the users of these materials as to the toxic characteristics and the control measures needed to ensure their safe use. The program also provides a continuing record of the toxic substances procured, who procured them, what other toxic substances the user has obtained in the past, and where similar materials have been used elsewhere at the center.

  12. Gene Transcription, Metabolite and Lipid Profiling in Eco-Indicator Daphnia magna Indicate Diverse Mechanisms of Toxicity by Legacy and Emerging Flame-Retardants

    EPA Science Inventory

    The use of chemical flame-retardants (FR) in consumer products has steadily increased over the last 30 years. Toxicity data exist for legacy FRs such as pentabromodiphenyl ether (pentaBDE), but less is known about effects of new formulations. To address this issue, the toxicity o...

  13. Comparative Toxicity and Dosimetric Profile of Whole-Pelvis Versus Prostate Bed-Only Intensity-Modulated Radiation Therapy After Prostatectomy

    SciTech Connect

    Deville, Curtiland; Vapiwala, Neha; Hwang, Wei-Ting; Lin Haibo; Bar Ad, Voichita; Tochner, Zelig; Both, Stefan

    2012-03-15

    Purpose: To assess whether whole-pelvis (WP) intensity modulated radiation therapy (IMRT) for prostate cancer (PCa) after prostatectomy is associated with increased toxicity compared to prostate-bed only (PB) IMRT. Methods and Materials: All patients (n = 67) undergoing postprostatectomy IMRT to 70.2 Gy at our institution from January 2006 to January 2009 with minimum 12-month follow-up were divided into WP (n = 36) and PB (n = 31) comparison groups. WP patients received initial pelvic nodal IMRT to 45 Gy. Pretreatment demographics, bladder and rectal dose-volume histograms, and maximum genitourinary (GU) and gastrointestinal (GI) toxicities were compared. Logistic regression models evaluated uni- and multivariate associations between pretreatment demographics and toxicities. Results: Pretreatment demographics including age and comorbidities were similar between groups. WP patients had higher Gleason scores, T stages, and preoperative prostate-specific antigen (PSA) levels, and more WP patients underwent androgen deprivation therapy (ADT). WP minimum (Dmin) and mean bladder doses, bladder volumes receiving more than 5 Gy (V5) and V20, rectal Dmin, and PB bladder and rectal V65 were significantly increased. Maximum acute GI toxicity was Grade 2 and was increased for WP (61%) vs. PB (29%) patients (p = 0.001); there was no significant difference in acute Grade {>=}2 GU toxicity (22% WP vs. 10% PB; p = 0.193), late Grade {>=}2 GI toxicity (3% WP vs. 0% PB; p = 0.678), or late Grade {>=}2 GU toxicity (28% WP vs. 19% PB; p = 0.274) with 25-month median follow-up (range, 12-44 months). On multivariate analysis, long-term ADT use was associated with Grade {>=}2 late GU toxicity (p = 0.02). Conclusion: Despite dosimetric differences in irradiated bowel, bladder, and rectum, WP IMRT resulted only in clinically significant increased acute GI toxicity in comparison to that with PB IMRT, with no differences in GU or late GI toxicity.

  14. Profiling the activity of environmental chemicals in prenatal developmental toxicity studies using the U.S. EPA’s ToxRefDB

    EPA Science Inventory

    As the primary source for regulatory developmental toxicity information, prenatal studies characterize maternal effects and fetal endpoints including malformations, resorptions, and fetal weight reduction. Results from 383 rat and 368 rabbit prenatal studies on 387 chemicals, mo...

  15. Profiling of the toxicity mechanisms of coated and uncoated silver nanoparticles to yeast Saccharomyces cerevisiae BY4741 using a set of its 9 single-gene deletion mutants defective in oxidative stress response, cell wall or membrane integrity and endocytosis.

    PubMed

    Käosaar, Sandra; Kahru, Anne; Mantecca, Paride; Kasemets, Kaja

    2016-09-01

    The widespread use of nanosilver in various antibacterial, antifungal, and antiviral products warrants the studies of the toxicity pathways of nanosilver-enabled materials toward microbes and viruses. We profiled the toxicity mechanisms of uncoated, casein-coated, and polyvinylpyrrolidone-coated silver nanoparticles (AgNPs) using Saccharomyces cerevisiae wild-type (wt) and its 9 single-gene deletion mutants defective in oxidative stress (OS) defense, cell wall/membrane integrity, and endocytosis. The 48-h growth inhibition assay in organic-rich growth medium and 24-h cell viability assay in deionized (DI) water were applied whereas AgNO3, H2O2, and SDS served as positive controls. Both coated AgNPs (primary size 8-12nm) were significantly more toxic than the uncoated (~85nm) AgNPs. All studied AgNPs were ~30 times more toxic if exposed to yeast cells in DI water than in the rich growth medium: the IC50 based on nominal concentration of AgNPs in the growth inhibition test ranged from 77 to 576mg Ag/L and in the cell viability test from 2.7 to 18.7mg Ag/L, respectively. Confocal microscopy showed that wt but not endocytosis mutant (end3Δ) internalized AgNPs. Comparison of toxicity patterns of wt and mutant strains defective in OS defense and membrane integrity revealed that the toxicity of the studied AgNPs to S. cerevisiae was not caused by the OS or cell wall/membrane permeabilization. PMID:27260961

  16. Profiling and Racial Profiling: An Interactive Exercise

    ERIC Educational Resources Information Center

    Semple, Philip

    2013-01-01

    Racial Profiling has been recognized as a serious problem that affects many segments of our society and is especially notable in law enforcement. Governments and police services have pronounced that racial profiling is not acceptable and will not be tolerated. They have gone to great lengths in trying to eradicate racial profiling through…

  17. Adenovirus type 35-vectored tuberculosis vaccine has an acceptable safety and tolerability profile in healthy, BCG-vaccinated, QuantiFERON(®)-TB Gold (+) Kenyan adults without evidence of tuberculosis.

    PubMed

    Walsh, Douglas S; Owira, Victorine; Polhemus, Mark; Otieno, Lucas; Andagalu, Ben; Ogutu, Bernhards; Waitumbi, John; Hawkridge, Anthony; Shepherd, Barbara; Pau, Maria Grazia; Sadoff, Jerald; Douoguih, Macaya; McClain, J Bruce

    2016-05-01

    In a Phase 1 trial, we evaluated the safety of AERAS-402, an adenovirus 35-vectored TB vaccine candidate expressing 3 Mycobacterium tuberculosis (Mtb) immunodominant antigens, in subjects with and without latent Mtb infection. HIV-negative, BCG-vaccinated Kenyan adults without evidence of tuberculosis, 10 QuantiFERON(®)-TB Gold In-Tube test (QFT-G)(-) and 10 QFT-G(+), were randomized 4:1 to receive AERAS-402 or placebo as two doses, on Days 0 and 56, with follow up to Day 182. There were no deaths, serious adverse events or withdrawals. For 1 AERAS-402 QFT-G(-) and 1 AERAS-402 QFT-G(+) subject, there were 3 self-limiting severe AEs of injection site pain: 1 after the first vaccination and 1 after each vaccination, respectively. Two additional severe AEs considered vaccine-related were reported after the first vaccination in AERAS-402 QFT-G(+) subjects: elevated blood creatine phosphokinase and neutropenia, the latter slowly improving but remaining abnormal until study end. AERAS-402 was not detected in urine or throat cultures for any subject. In intracellular cytokine staining studies, curtailed by technical issues, we saw modest CD4+ and CD8+ T cell responses to Mtb Ag85A/b peptide pools among both QFT-G(-) and (+) subjects, with trends in the CD4+ T cells suggestive of boosting after the second vaccine dose, slightly more so in QFT-G(+) subjects. CD4+ and CD8+ responses to Mtb antigen TB10.4 were minimal. Increases in Adenovirus 35 neutralizing antibodies from screening to end of study, seen in 50% of AERAS-402 recipients, were mostly minimal. This small study confirms acceptable safety and tolerability profiles for AERAS-402, in line with other Phase 1 studies of AERAS-402, now to include QFT-G(+) subjects. PMID:27026148

  18. Genome-Wide Functional and Stress Response Profiling Reveals Toxic Mechanism and Genes Required for Tolerance to Benzo[a]pyrene in S. cerevisiae

    PubMed Central

    O’Connor, Sean Timothy Francis; Lan, Jiaqi; North, Matthew; Loguinov, Alexandre; Zhang, Luoping; Smith, Martyn T.; Gu, April Z.; Vulpe, Chris

    2012-01-01

    Benzo[a]pyrene (BaP) is a ubiquitous, potent, and complete carcinogen resulting from incomplete organic combustion. BaP can form DNA adducts but other mechanisms may play a role in toxicity. We used a functional toxicology approach in S. cerevisiae to assess the genetic requirements for cellular resistance to BaP. In addition, we examined translational activities of key genes involved in various stress response pathways. We identified multiple genes and processes involved in modulating BaP toxicity in yeast which support DNA damage as a primary mechanism of toxicity, but also identify other potential toxicity pathways. Gene ontology enrichment analysis indicated that DNA damage and repair as well as redox homeostasis and oxidative stress are key processes in cellular response to BaP suggesting a similar mode of action of BaP in yeast and mammals. Interestingly, toxicant export is also implicated as a potential novel modulator of cellular susceptibility. In particular, we identified several transporters with human orthologs (solute carrier family 22) which may play a role in mammalian systems. PMID:23403841

  19. Intra-articular administration of lidocaine plus adrenaline in dogs: Pharmacokinetic profile and evaluation of toxicity in vivo and in vitro.

    PubMed

    Di Salvo, A; Chiaradia, E; Della Rocca, G; Mancini, F; Galarini, R; Giusepponi, D; De Monte, V; Cagnardi, P; Marenzoni, M L; Bufalari, A

    2016-02-01

    The aim of this study was to evaluate the safety of intra-articular (IA) lidocaine plus adrenaline for improving peri-operative analgesia in anaesthetized dogs undergoing arthroscopy of the elbow. A solution of lidocaine (L) 1.98% plus adrenaline 1:100.000 was administered via the IA route and its safety evaluated in terms of cardio-, neuro-, and chondro-toxicity. No bradycardia or hypotension was recorded from induction to the last observational time point. Signs of toxicity of the nervous system could have been masked by the general anaesthesia but lidocaine concentrations detected in the blood were lower than those thought to be capable of producing toxicity. The assessment of in vitro chondrotoxicity showed a dose- and time-dependent effect of lidocaine on the viability of articular cells. Adrenaline appeared to reduce the chondrotoxicity of 1% lidocaine, following an exposure of up to 30 min. PMID:26681138

  20. Survey of receiving-water environmental impacts associated with discharges from pulp mills; 1: Mill characteristics, receiving-water chemical profiles and lab toxicity tests

    SciTech Connect

    Robinson, R.D. . Dept. of Environmental Biology); Carey, J.H. . Rivers Research Branch); Solomon, K.R. ); Smith, I.R. . Water Resources Branch); Servos, M.R.; Munkittrick, K.R. . Great Lakes Lab. for Fisheries and Aquatic Sciences)

    1994-07-01

    This survey examined the relationship between environmental responses at pulp mill sites and the pulping process, effluent treatment, and bleaching technology used by pulp mills. This manuscript is the first in a series of four; it reviews the location and operating characteristics of mills included in the survey and provides background information on water chemistry that is relevant to the other components of the survey. In addition, lab 7-d toxicity tests of receiving water were conducted using fathead minnows (Pimephales promelas) and the cladoceran Ceriodaphnia dubia with water samples collected upstream and downstream of effluent discharges at 11 Canadian pulp and paper mills; these samples were collected at the same time as fish surveys were conducted. Survival of fathead minnow larvae was significantly reduced at four of the 11 downstream sites. Ceriodaphnia reproduction was significantly higher at six of the 11 downstream sites and significantly lower at two downstream sites. There were no significant effects on fathead minnow larva growth or adult Ceriodaphnia survival at any of the examined downstream sites. Negative effects in the toxicity tests were generally associated with the low dilution discharge of primary treated effluent with a previous history of acute toxicity. Fathead minnow and Ceriodaphnia tests were generally correlated with historical data on benthic macroinvertebrate community responses. Neither toxicity test predicted the physiological changes in wild fish that are presented in accompanying papers.

  1. Cytochrome P450 Expression Profile of the PICM-19H Pig Liver Cell Line: Potential Application to Rapid Liver Toxicity Assays.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In vitro models of the liver are needed to replace animal models for the rapid assessment of drug biotransformation and toxicity. One hepatocellular model, the PICM-19 pig liver stem cell line, may fulfill this need since these cells have many activities associated with xenobiotic phase I and phas...

  2. Fatty Acid-Derived Pro-Toxicants of the Rat Selective Toxicant Norbormide.

    PubMed

    Choi, Hans; Conole, Daniel; Atkinson, Darcy J; Laita, Olivia; Jay-Smith, Morgan; Pagano, Mario Angelo; Ribaudo, Giovanni; Cavalli, Maurizio; Bova, Sergio; Hopkins, Brian; Brimble, Margaret A; Rennison, David

    2016-06-01

    Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents and mammals. However, as an acute vasoactive, NRB has a rapid onset of action which makes it relatively unpalatable to rats, often leading to sublethal uptake and accompanying bait shyness. A series of NRB-derived pro-toxicants (3a - i, 4a - i, and 5a - i) were prepared in an effort to 'mask' this acute response and improve both palatability and efficacy. Their synthesis, in vitro biological evaluation (vasocontractile response in rat vasculature, stability in selected rat media) and palatability/efficacy in Sprague-Dawley, wild Norway, and wild ship rats is described. Most notably, pro-toxicant 3d was revealed to be free of all pre-cleavage vasoconstrictory activity in rat caudal artery and was subsequently demonstrated to release NRB in the presence of rat blood, liver, and pancreatic enzymes. Moreover, it consistently displayed a high level of acceptance by rats in a two-choice bait-palatability and efficacy trial, with accompanying high mortality. On this evidence, fatty acid ester prodrugs would appear to offer a promising platform for the further development of NRB-derived toxicants with enhanced palatability and efficacy profiles. PMID:27144301

  3. Developmental Toxicity

    EPA Science Inventory

    This chapter provides an overview the developmental toxicity resulting from exposure to perfluorinated alkyl acids (PFAAs). The majority of studies of PFAA-induced developmental toxicity have examined effects of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) a...

  4. Social Acceptance of Wind: A Brief Overview (Presentation)

    SciTech Connect

    Lantz, E.

    2015-01-01

    This presentation discusses concepts and trends in social acceptance of wind energy, profiles recent research findings, and discussions mitigation strategies intended to resolve wind power social acceptance challenges as informed by published research and the experiences of individuals participating in the International Energy Agencies Working Group on Social Acceptance of Wind Energy

  5. Laser ablation ICP-MS profiling and semiquantitative determination of trace element concentrations in desert tortoise shells: Documenting the uptake of elemental toxicants

    USGS Publications Warehouse

    Seltzer, M.D.; Berry, K.H.

    2005-01-01

    The outer keratin layer (scute) of desert tortoise shells consists of incrementally grown laminae in which various bioaccumulated trace elements are sequestered during scute deposition. Laser ablation ICP-MS examination of laminae in scutes of dead tortoises revealed patterns of trace elemental distribution from which the chronology of elemental uptake can be inferred. These patterns may be of pathologic significance in the case of elemental toxicants such as arsenic, which has been linked to both shell and respiratory diseases. Laser ablation transects, performed along the lateral surfaces of sectioned scutes, offered the most successful means of avoiding exogenous contamination that was present on the scute exterior. Semiquantitative determination of elemental concentrations was achieved using sulfur, a keratin matrix element, as an internal standard. The results presented here highlight the potential of laser ablation ICP-MS as a diagnostic tool for investigating toxic element uptake as it pertains to tortoise morbidity and mortality.

  6. Laser ablation ICP-MS profiling and semiquantitative determination of trace element concentrations in desert tortoise shells: documenting the uptake of elemental toxicants.

    PubMed

    Seltzer, Michaeld; Berry, Kristinh

    2005-03-01

    The outer keratin layer (scute) of desert tortoise shells consists of incrementally grown laminae in which various bioaccumulated trace elements are sequestered during scute deposition. Laser ablation ICP-MS examination of laminae in scutes of dead tortoises revealed patterns of trace elemental distribution from which the chronology of elemental uptake can be inferred. These patterns may be of pathologic significance in the case of elemental toxicants such as arsenic, which has been linked to both shell and respiratory diseases. Laser ablation transects, performed along the lateral surfaces of sectioned scutes, offered the most successful means of avoiding exogenous contamination that was present on the scute exterior. Semiquantitative determination of elemental concentrations was achieved using sulfur, a keratin matrix element, as an internal standard. The results presented here highlight the potential of laser ablation ICP-MS as a diagnostic tool for investigating toxic element uptake as it pertains to tortoise morbidity and mortality. PMID:15740773

  7. (I) Pharmacological profiling of a novel modulator of the α7 nicotinic receptor: Blockade of a toxic acetylcholinesterase-derived peptide increased in Alzheimer brains.

    PubMed

    Garcia-Ratés, Sara; Morrill, Paul; Tu, Henry; Pottiez, Gwenael; Badin, Antoine-Scott; Tormo-Garcia, Cristina; Heffner, Catherine; Coen, Clive W; Greenfield, Susan A

    2016-06-01

    The primary cause of Alzheimer's disease is unlikely to be the much studied markers amyloid beta or tau. Their widespread distribution throughout the brain does not account for the specific identity and deep subcortical location of the primarily vulnerable neurons. Moreover an unusual and intriguing feature of these neurons is that, despite their diverse transmitters, they all contain acetylcholinesterase. Here we show for the first time that (1) a peptide derived from acetylcholinesterase, with independent trophic functions that turn toxic in maturity, is significantly raised in the Alzheimer midbrain and cerebrospinal fluid; (2) a synthetic version of this peptide enhances calcium influx and eventual production of amyloid beta and tau phosphorylation via an allosteric site on the α7 nicotinic receptor; (3) a synthetic cyclic version of this peptide is neuroprotective against the toxicity not only of its linear counterpart but also of amyloid beta, thereby opening up the prospect of a novel therapeutic approach. PMID:26867503

  8. Does Image-Guided Radiotherapy Improve Toxicity Profile in Whole Pelvic-Treated High-Risk Prostate Cancer? Comparison Between IG-IMRT and IMRT

    SciTech Connect

    Chung, Hans T. Xia Ping; Chan, Linda W.; Park-Somers, Eileen; Roach, Mack

    2009-01-01

    Purpose: To evaluate the impact of adding image-guided (IG) technique to intensity-modulated radiotherapy (IMRT) on dosimetric avoidance of organs at risk (OAR) and acute toxicities. Methods and Materials: A total of 25 consecutively treated patients (10 from National University Hospital and 15 from University of California San Francisco) with high-risk prostate cancer formed the study cohort. All received definitive IMRT with prophylactic nodal RT. Similar IMRT contouring and planning techniques were used at both centers. At University of California, San Francisco, intraprostatic fiducial markers were used for daily pretreatment on-line corrections (IG-IMRT). In contrast, at the National University Hospital, no fiducial markers were used (IMRT). At University of California, San Francisco, the planning target volume margins to the prostate were 2-3 mm. At the National University Hospital, they were 1 cm circumferentially, except for 0.5 cm posteriorly. The acute rectal and bladder toxicities and dosimetric endpoints to the planning target volume and organs at risk were compared. Results: The planning target volume dose coverage was not significantly different between IMRT and IG-IMRT for the prostate, seminal vesicles, and lymph nodes. The volume of rectum and bladder receiving {>=}40, {>=}60, and {>=}70 Gy were all significantly less using IG-IMRT (p <0.001). IG-IMRT yielded lower acute Radiation Therapy Oncology Group Grade 2 rectal (80% vs. 13%, p = 0.004) and bladder (60% vs. 13%, p = 0.014) toxicities. Conclusions: IG-IMRT, using daily target localization with fiducial markers, permits the use of smaller margins and correspondingly lower doses to the organs at risk, such as the rectum and bladder. These tangible gains appear to translate into lower clinically significant toxicities.

  9. Comparative In Vitro Toxicity Profile of Electronic and Tobacco Cigarettes, Smokeless Tobacco and Nicotine Replacement Therapy Products: E-Liquids, Extracts and Collected Aerosols

    PubMed Central

    Misra, Manoj; Leverette, Robert D.; Cooper, Bethany T.; Bennett, Melanee B.; Brown, Steven E.

    2014-01-01

    The use of electronic cigarettes (e-cigs) continues to increase worldwide in parallel with accumulating information on their potential toxicity and safety. In this study, an in vitro battery of established assays was used to examine the cytotoxicity, mutagenicity, genotoxicity and inflammatory responses of certain commercial e-cigs and compared to tobacco burning cigarettes, smokeless tobacco (SLT) products and a nicotine replacement therapy (NRT) product. The toxicity evaluation was performed on e-liquids and pad-collected aerosols of e-cigs, pad-collected smoke condensates of tobacco cigarettes and extracts of SLT and NRT products. In all assays, exposures with e-cig liquids and collected aerosols, at the doses tested, showed no significant activity when compared to tobacco burning cigarettes. Results for the e-cigs, with and without nicotine in two evaluated flavor variants, were very similar in all assays, indicating that the presence of nicotine and flavors, at the levels tested, did not induce any cytotoxic, genotoxic or inflammatory effects. The present findings indicate that neither the e-cig liquids and collected aerosols, nor the extracts of the SLT and NRT products produce any meaningful toxic effects in four widely-applied in vitro test systems, in which the conventional cigarette smoke preparations, at comparable exposures, are markedly cytotoxic and genotoxic. PMID:25361047

  10. Toxicity Studies.

    PubMed

    2016-01-01

    Toxicity studies in the animal models are done to determine the dose level recommended for the treatment of disease as drug. This guideline enables the characterization of adverse effects following repeated daily inhalation exposure to a test. This chapter includes oral and dermal toxicity studies which are discussed as per OECD guidelines. Both acute and subacute toxicity studies are given special emphasis. PMID:26939270

  11. Toxicity profile and clinical outcomes in locally advanced head and neck cancer patients treated with induction chemotherapy prior to concurrent chemoradiation.

    PubMed

    Ko, Eric C; Genden, Eric M; Misiukiewicz, Krzysztof; Som, Peter M; Kostakoglu, Lale; Chen, Chien-Ting; Packer, Stuart; Kao, Johnny

    2012-02-01

    The use of induction chemotherapy prior to chemoradiation for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) remains controversial. We explored whether toxicity from induction chemotherapy influenced the delivery of concurrent chemoradiation. Among 171 consecutive previously unirradiated patients with HNSCC treated with combined chemotherapy and radiation, we identified 66 patients with stage III-IVB head and neck carcinoma who were treated with induction chemotherapy prior to planned chemoradiation. The most common induction regimen was docetaxel, cisplatin and 5-FU (TPF; 80%) for 2 to 3 cycles. Mean radiation dose was 72 Gy (range, 36-75 Gy). Concurrent chemotherapy regimens included cisplatin (26%), cetuximab (5%) and 5-fluorouracil/hydroxyurea (65%)-based regimens. At a median follow-up of 27 months (range, 9-56 months), the 2-year locoregional control and distant control rates were 85 and 86%, respectively. The 2-year disease-free survival and overall survival rates were 74 and 80%, respectively. Although there were no grade 5 toxicities during induction chemotherapy, 26% of patients required hospitalization for adverse events, including 5% needing intensive care. The most common high grade adverse events were grade 4 neutropenia (21%) and neutropenic fever (17%). Six percent of patients were unable to tolerate concurrent chemotherapy. The 2-year disease-free survival was significantly higher in patients able to complete induction and concurrent chemoradiation as planned (83 vs. 27%, p<0.001). Induction chemotherapy followed by concurrent chemoradiation results in promising survival rates in our cohort of advanced head and neck carcinoma patients. Due to severe toxicities in a subset of patients, this strategy is only recommended in selected high-risk patients who are carefully followed by an experienced multidisciplinary team. PMID:22020564

  12. Health and environmental effects profile for chlorthiophos

    SciTech Connect

    Not Available

    1986-04-01

    The Health and Environmental Effects Profile for Chlorthiophos was prepared to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Chlorthiophos has been determined to be a systemic toxicant. An Acceptable Daily Intake (ADI), for chlorthiophos is 0.8 microgram/kg/day for oral exposure. The Reportable Quantity (RQ) value of 1, 10, 100, 1000 or 500 pounds is used to determine the quantity of a hazardous substance for which notification is required in the event of a release as specified by CERCLA based on chronic toxicity. Existing data are insufficient to determine an RQ value.

  13. Radiation treatment with volumetric modulated arc therapy of hepatocellular carcinoma patients. Early clinical outcome and toxicity profile from a retrospective analysis of 138 patients

    PubMed Central

    2012-01-01

    Background To report early outcome and toxicity for inoperable patients with hepatocellular carcinoma (HCC) treated with volumetric modulated arc therapy (VMAT). Methods One hundred and thirty eight patients were retrospectively analysed. Dose prescription ranged from 45 to 66Gy with conventional fractionation regime. Based on AJCC staging, 88.4% presented stage III or IV. Two-thirds (69.6%) were Child-Pugh stage A, the remaining were stage B. According to Barcelona Clinic Liver Cancer staging, 72.5% of patients were classified as stage C. Results Median age was 66 years, median tumor volume was 516cm3 (28 to 3620cm3). The most patients (83%) were treated with 60Gy. Median follow-up time was 9 months. One-year overall survival rate was 45% (100% for AJCC stage I, 83% for stage II, 45% for stage III and 28% for stage IV), median survival was 10.3 months (95% C.I. 7.2-13.3). Local control was achieved in 94% (of 109 assessable patients), stable disease in 29%, partial response in 53%, complete response in 11%, and progression in 6%. Radiation-induced liver disease was observed in 34 patients (25%). Gastrointestinal grade 3 toxicity was modest with a total of 17 (12.3%) cases for all endpoints. Conclusions Clinical results could suggest to introduce VMAT as an appropriate technique for the patients with HCC. PMID:23216929

  14. Ocular toxicity of fludarabine

    PubMed Central

    Ding, Xiaoyan; Herzlich, Alexandra A; Bishop, Rachel; Tuo, Jingsheng; Chan, Chi-Chao

    2008-01-01

    The purine analogs, fludarabine and cladribine represent an important class of chemotherapy agents used to treat a broad spectrum of lymphoid malignancies. Their toxicity profiles include dose-limiting myelosuppression, immunosuppression, opportunistic infection and severe neurotoxicity. This review summarizes the neurotoxicity of high- and standard-dose fludarabine, focusing on the clinical and pathological manifestations in the eye. The mechanisms of ocular toxicity are probably multifactorial. With increasing clinical use, an awareness of the neurological and ocular vulnerability, particularly to fludarabine, is important owing to the potential for life- and sight-threatening consequences. PMID:18461151

  15. ATLAS ACCEPTANCE TEST

    SciTech Connect

    J.C. COCHRANE; J.V. PARKER; ET AL

    2001-06-01

    The acceptance test program for Atlas, a 23 MJ pulsed power facility for use in the Los Alamos High Energy Density Hydrodynamics program, has been completed. Completion of this program officially releases Atlas from the construction phase and readies it for experiments. Details of the acceptance test program results and of machine capabilities for experiments will be presented.

  16. Identification and confirmation of ammonia toxicity in contaminated sediments using a modified toxicity identification evaluation approach

    SciTech Connect

    Sprang, P.A. Van; Janssen, C.R.

    1997-12-01

    Toxicity identification of sediment pore waters from four sites in the Upper Scheldt (Belgium) was assessed using a simplified and discriminative toxicity identification evaluation procedure. The samples from all locations exhibited acute toxicity toward the freshwater crustacean Thamnocephalus platyurus. Toxicity was removed or considerably reduced by the cation exchange resins and air stripping at pH 11. In addition, the toxicity of the pore waters was found to be highly pH dependent. Increased toxicity was observed at higher pH levels, whereas reduced toxicity was found at lower pH levels. Based on these results, ammonia was suggested as the main toxic agent. The presence of ammonia concentrations exceeding the 24-h median lethal concentration and comparison of the toxicity characterization profiles of the pore waters with those of the suspected toxicant supported this hypothesis. Furthermore, a significant positive correlation between the observed toxicity of the pore waters and the expected toxicity (due to the presence of the suspected toxicant) confirmed ammonia as the true toxic agent. Finally, the ratio between the expected ammonia toxicity and the observed toxicity from the characterization tests was approx. 1, meaning that all or most of the observed toxicity was caused by the presence of one toxicant (i.e., ammonia). The developed toxicity identification evaluation procedure is suggested as a useful tool for the identification and confirmation of toxicants in contaminated sediments.

  17. Toxicity and safety of topical sodium hypochlorite.

    PubMed

    Bruch, Mary K

    2007-01-01

    The safety and toxicity of sodium hypochlorite is reviewed with particular correlation to topical use. Since sodium hypochlorite is one of the most widely used chemicals in the environment, its safety has been established by long use and toxicity profile. This chapter reviews recent toxicology testing including routine systemic LD50, topical LD50, topical toxicology, irritation and sensitization. The resulting toxicity or safety profile clarifies the safe topical use of electrolytically produced sodium hypochlorite solution (ExSept, Amuchina 10%). PMID:17099299

  18. Toxicogenomics profiling of bone marrow from rats treated with topotecan in combination with oxaliplatin: a mechanistic strategy to inform combination toxicity

    PubMed Central

    Davis, Myrtle; Li, Jianying; Knight, Elaine; Eldridge, Sandy R.; Daniels, Kellye K.; Bushel, Pierre R.

    2015-01-01

    Combinations of anticancer agents may have synergistic anti-tumor effects, but enhanced hematological toxicity often limit their clinical use. We examined whether “microarray profiles” could be used to compare early molecular responses following a single dose of agents administered individually with that of the agents administered in a combination. We compared the mRNA responses within bone marrow of Sprague-Dawley rats after a single 30 min treatment with topotecan at 4.7 mg/kg or oxaliplatin at 15 mg/kg alone to that of sequentially administered combination therapy or vehicle control for 1, 6, and 24 h. We also examined the histopathology of the bone marrow following all treatments. Drug-related histopathological lesions were limited to bone marrow hypocellularity for animals dosed with either agent alone or in combination. Lesions had an earlier onset and higher incidence for animals given topotecan alone or in combination with oxaliplatin. Severity increased from mild to moderate when topotecan was administered prior to oxaliplatin compared with administering oxaliplatin first. Notably, six patterns of co-expressed genes were detected at the 1 h time point that indicate regulatory expression of genes that are dependent on the order of the administration. These results suggest alterations in histone biology, chromatin remodeling, DNA repair, bone regeneration, and respiratory and oxidative phosphorylation are among the prominent pathways modulated in bone marrow from animals treated with an oxaliplatin/topotecan combination. These data also demonstrate the potential for early mRNA patterns derived from target organs of toxicity to inform toxicological risk and molecular mechanisms for agents given in combination. PMID:25729387

  19. Toxic Encephalopathy

    PubMed Central

    Kim, Jae Woo

    2012-01-01

    This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure. PMID:23251840

  20. [Toxic polyneuropathies].

    PubMed

    Neundörfer, B

    1992-08-01

    Toxic factors may have damaging effects on the peripheral nerves at different sites: on the axon, on the myelin sheath, on the cell bodies and on the vasa nervorum. The toxic neuropathies can be divided up into polyneuropathies induced by drugs, by industrial, environmental and stimulant poisons. Mostly symmetrical sensory symptoms and signs are the first disturbances, often followed by symmetrical motor pareses. Some polyneuropathies induced by amiodarone, benzene, lead, cimetidine, chloroquine, dapsone, gentamycin, gold, imipramine, hexacarbons, nialamide, penicillin, triorthocresylphosphate and vincristine are primarily dominated by motory losses. Polyneuropathies induced by amitriptyline, ethylene, oxide, lead, chlorprothixene, heroin, hydralazine, methaqualone, nialamide and penicillin show an asymmetrical distribution pattern of the neural losses. In some types of toxic polyneuropathies the cranial nerves and the autonomic nerves are particularly involved. The clinical symptomatology of the most important types of toxic neuropathies are described shortly. The best therapy is, of course, termination of exposure to the toxic substance concerned. PMID:1509644

  1. Acceptance, values, and probability.

    PubMed

    Steel, Daniel

    2015-10-01

    This essay makes a case for regarding personal probabilities used in Bayesian analyses of confirmation as objects of acceptance and rejection. That in turn entails that personal probabilities are subject to the argument from inductive risk, which aims to show non-epistemic values can legitimately influence scientific decisions about which hypotheses to accept. In a Bayesian context, the argument from inductive risk suggests that value judgments can influence decisions about which probability models to accept for likelihoods and priors. As a consequence, if the argument from inductive risk is sound, then non-epistemic values can affect not only the level of evidence deemed necessary to accept a hypothesis but also degrees of confirmation themselves. PMID:26386533

  2. Newbery Medal Acceptance.

    ERIC Educational Resources Information Center

    Freedman, Russell

    1988-01-01

    Presents the Newbery Medal acceptance speech of Russell Freedman, writer of children's nonfiction. Discusses the place of nonfiction in the world of children's literature, the evolution of children's biographies, and the author's work on "Lincoln." (ARH)

  3. Newbery Medal Acceptance.

    ERIC Educational Resources Information Center

    Cleary, Beverly

    1984-01-01

    Reprints the text of Ms. Cleary's Newbery medal acceptance speech in which she gives personal history concerning her development as a writer and her response to the letters she receives from children. (CRH)

  4. Caldecott Medal Acceptance.

    ERIC Educational Resources Information Center

    Provensen, Alice; Provensen, Martin

    1984-01-01

    Reprints the text of the Provensens' Caldecott medal acceptance speech in which they describe their early interest in libraries and literature, the collaborative aspect of their work, and their current interest in aviation. (CRH)

  5. PFOS, PFNA, and PFOA sub-lethal exposure to embryonic zebrafish have different toxicity profiles in terms of morphometrics, behavior and gene expression.

    PubMed

    Jantzen, Carrie E; Annunziato, Kate A; Bugel, Sean M; Cooper, Keith R

    2016-06-01

    Polyfluorinated compounds (PFC) are a class of anthropogenic, persistent and toxic chemicals. PFCs are detected worldwide and consist of fluorinated carbon chains of varying length, terminal groups, and industrial uses. Previous zebrafish studies in the literature as well as our own studies have shown that exposure to these chemicals at a low range of concentrations (0.02-2.0μM; 20-2000ppb) resulted in chemical specific developmental defects and reduced post hatch survival. It was hypothesized that sub-lethal embryonic exposure to perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), or perfluorooctanoic acid (PFOA) would result in different responses with regard to morphometric, behavior, and gene expression in both yolk sac fry and larval zebrafish. Zebrafish were exposed to PFOS, PFOA, and PFNA (0.02, 0.2, 2.0μM) for the first five days post fertilization (dpf) and analyzed for morphometrics (5 dpf, 14 dpf), targeted gene expression (5 dpf, 14 dpf), and locomotive behavior (14 dpf). All three PFCs commonly resulted in a decrease in total body length, increased tfc3a (muscle development) expression and decreased ap1s (protein transport) expression at 5dpf, and hyperactive locomotor activity 14 dpf. All other endpoints measured at both life-stage time points varied between each of the PFCs. PFOS, PFNA, and PFOA exposure resulted in significantly altered responses in terms of morphometric, locomotion, and gene expression endpoints, which could be manifested in field exposed teleosts. PMID:27058923

  6. Borocaptate sodium (BSH) toxicity issues

    SciTech Connect

    LaHann, T.

    1995-11-01

    ISU`s Center for Toxicology Research has been conducting toxicity testing of borocaptate sodium (BSH) to aid in assessing if proposed human studies of BSH are likely to be acceptably safe. This report describes BSH interactions with other biological agents.

  7. Identifying the cause of toxicity in an algal whole effluent toxicity study - an unanticipated toxicant.

    PubMed

    Naddy, Rami B; Tapp, Kelly; Rehner, Anita B; Pillard, David A; Schrage, Laura

    2011-10-01

    Toxicity was observed in whole effluent toxicity (WET) studies with the freshwater alga, Pseudokirchneriella subcapitata, in three consecutive monthly studies, (NOEC=50-75%). Toxicity was not observed to Ceriodaphnia dubia or the fathead minnow, Pimephales promelas in concurrent studies. Selected toxicity identification evaluation (TIE) tests were conducted in a tiered approach to eliminate possible toxicants and progressively identify the causative agent. Filtration following alkaline adjustment (pH 10 or 11) was effective in eliminating significant growth effects and also reduced phosphate concentration. The TIE studies confirmed that the observed effluent toxicity was caused by excess ortho-phosphate in the effluent not by overstimulation or related to unfavorable N:P ratios; but due to direct toxicity. The 96-h 25% inhibition concentration (IC25) of ortho-phosphate to P. subcapitata was 3.4 mg L⁻¹ while the maximum acceptable toxicant concentration was 4.8 mg L⁻¹. This study illustrates the value of multi-species testing and also provides an example of an effective TIE using algae identifying an unanticipated toxicant. PMID:21840029

  8. Ecdysone-Related Biomarkers of Toxicity in the Model Organism Chironomus riparius: Stage and Sex-Dependent Variations in Gene Expression Profiles

    PubMed Central

    Gómez-Sande, Pablo; Ozáez, Irene; Cobo, Fernando; Servia, María J.

    2015-01-01

    Despite being considered a model organism in toxicity studies, particularly in assessing the environmental impact of endocrine disrupting compounds (EDCs) and other chemicals, the molecular basis of development is largely unknown in Chironomus riparius. We have characterized the expression patterns of important genes involved in the ecdysone pathway from embryos to pupa, but specially during the different phases of C. riparius fourth larval instar, according to the development of genital and thoracic imaginal discs. Real-Time PCR was used to analyze: EcR and usp, two genes encoding the two dimerizing partners of the functional ecdysone receptor; E74, an early response gene induced by ecdysteroids; vg (vitellogenin), an effector gene; hsp70 and hsc70, two heat-shock genes involved in the correct folding of the ecdysone receptor; and rpL13, as a part of the ribosomal machinery. Our results show for the first time stage and sex-dependent variations in ecdysone-responsive genes, specially during the late larval stage of C. riparius. The induction in the expression of EcR and usp during the VII-VIII phase of the fourth instar is concomitant with a coordinated response in the activity of the other genes analyzed, suggesting the moment where larvae prepare for pupation. This work is particularly relevant given that most of the analyzed genes have been proposed previously in this species as sensitive biomarkers for the toxicological evaluation of aquatic ecosystems. Identifying the natural regulation of these molecular endpoints throughout the Chironomus development will contribute to a more in-depth and accurate evaluation of the disrupting effects of EDCs in ecotoxicological studies. PMID:26448051

  9. Ecdysone-Related Biomarkers of Toxicity in the Model Organism Chironomus riparius: Stage and Sex-Dependent Variations in Gene Expression Profiles.

    PubMed

    Planelló, Rosario; Herrero, Óscar; Gómez-Sande, Pablo; Ozáez, Irene; Cobo, Fernando; Servia, María J

    2015-01-01

    Despite being considered a model organism in toxicity studies, particularly in assessing the environmental impact of endocrine disrupting compounds (EDCs) and other chemicals, the molecular basis of development is largely unknown in Chironomus riparius. We have characterized the expression patterns of important genes involved in the ecdysone pathway from embryos to pupa, but specially during the different phases of C. riparius fourth larval instar, according to the development of genital and thoracic imaginal discs. Real-Time PCR was used to analyze: EcR and usp, two genes encoding the two dimerizing partners of the functional ecdysone receptor; E74, an early response gene induced by ecdysteroids; vg (vitellogenin), an effector gene; hsp70 and hsc70, two heat-shock genes involved in the correct folding of the ecdysone receptor; and rpL13, as a part of the ribosomal machinery. Our results show for the first time stage and sex-dependent variations in ecdysone-responsive genes, specially during the late larval stage of C. riparius. The induction in the expression of EcR and usp during the VII-VIII phase of the fourth instar is concomitant with a coordinated response in the activity of the other genes analyzed, suggesting the moment where larvae prepare for pupation. This work is particularly relevant given that most of the analyzed genes have been proposed previously in this species as sensitive biomarkers for the toxicological evaluation of aquatic ecosystems. Identifying the natural regulation of these molecular endpoints throughout the Chironomus development will contribute to a more in-depth and accurate evaluation of the disrupting effects of EDCs in ecotoxicological studies. PMID:26448051

  10. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with 177Lu-DOTATATE

    PubMed Central

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium (177Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with 177Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites of

  11. Surviving in a toxic world: transcriptomics and gene expression profiling in response to environmental pollution in the critically endangered European eel

    PubMed Central

    2012-01-01

    Background Genomic and transcriptomic approaches have the potential for unveiling the genome-wide response to environmental perturbations. The abundance of the catadromous European eel (Anguilla anguilla) stock has been declining since the 1980s probably due to a combination of anthropogenic and climatic factors. In this paper, we explore the transcriptomic dynamics between individuals from high (river Tiber, Italy) and low pollution (lake Bolsena, Italy) environments, which were measured for 36 PCBs, several organochlorine pesticides and brominated flame retardants and nine metals. Results To this end, we first (i) updated the European eel transcriptome using deep sequencing data with a total of 640,040 reads assembled into 44,896 contigs (Eeelbase release 2.0), and (ii) developed a transcriptomic platform for global gene expression profiling in the critically endangered European eel of about 15,000 annotated contigs, which was applied to detect differentially expressed genes between polluted sites. Several detoxification genes related to metabolism of pollutants were upregulated in the highly polluted site, including genes that take part in phase I of the xenobiotic metabolism (CYP3A), phase II (glutathione-S-transferase) and oxidative stress (glutathione peroxidase). In addition, key genes in the mitochondrial respiratory chain and oxidative phosphorylation were down-regulated at the Tiber site relative to the Bolsena site. Conclusions Together with the induced high expression of detoxification genes, the suggested lowered expression of genes supposedly involved in metabolism suggests that pollution may also be associated with decreased respiratory and energy production. PMID:23009661

  12. Venom of the Coral Snake Micrurus clarki: Proteomic Profile, Toxicity, Immunological Cross-Neutralization, and Characterization of a Three-Finger Toxin.

    PubMed

    Lomonte, Bruno; Sasa, Mahmood; Rey-Suárez, Paola; Bryan, Wendy; Gutiérrez, José María

    2016-01-01

    Micrurus clarki is an uncommon coral snake distributed from the Southeastern Pacific of Costa Rica to Western Colombia, for which no information on its venom could be found in the literature. Using a 'venomics' approach, proteins of at least nine families were identified, with a moderate predominance of three-finger toxins (3FTx; 48.2%) over phospholipase A₂ (PLA₂; 36.5%). Comparison of this venom profile with those of other Micrurus species suggests that it may represent a more balanced, 'intermediate' type within the dichotomy between 3FTx- and PLA₂-predominant venoms. M. clarki venom was strongly cross-recognized and, accordingly, efficiently neutralized by an equine therapeutic antivenom against M. nigrocinctus, revealing their high antigenic similarity. Lethal activity for mice could be reproduced by a PLA₂ venom fraction, but, unexpectedly, not by fractions corresponding to 3FTxs. The most abundant venom component, hereby named clarkitoxin-I, was identified as a short-chain (type I) 3FTx, devoid of lethal effect in mice, whose target remains to be defined. Its amino acid sequence of 66 residues shows high similarity with predicted sequences of venom gland transcripts described for M. fulvius, M. browni, and M. diastema. PMID:27164141

  13. Accumulation and elimination profiles of paralytic shellfish poison in the short-necked clam Tapes japonica fed with the toxic dinoflagellate Gymnodinium catenatum.

    PubMed

    Samsur, Mohamad; Takatani, Tomohiro; Yamaguchi, Yasunaga; Sagara, Takefumi; Noguchi, Tamao; Arakawa, Osamu

    2007-02-01

    The paralytic shellfish poison (PSP)-producing dinoflagellate Gymnodinium catenatum (Gc) was fed to the short-necked clam Tapes japonica, and the accumulation, transformation and elimination profiles of PSP were investigated by means of high-performance liquid chromatography with postcolumn fluorescence derivatization (HPLC-FLD). The short-necked clams ingested most of the Gc cells (4 x 10(6) cells) supplied as a bolus at the beginning of the experiment, and accumulated a maximal amount of toxin (181 nmol/10 clams) after 12 hr. The rate of toxin accumulation at that time was 16%, which rapidly decreased thereafter. During the rearing period, a variation in toxin composition, derived presumably from the transformation of toxin analogues in the clams, was observed, including a reversal of the ratio of C2 to C1, and the appearance of carbamate (gonyautoxin (GTX) 2, 3) and decarbamoyl (dc) derivatives (decarbamoylsaxitoxin (dcSTX) and dcGTX2, 3), which were undetectable in Gc cells. The total amount of toxin contained in clams and residue (remaining Gc cells and/or excrement in the rearing tank) gradually declined, and only about 1% of the supplied toxin was detected at the end of the experiment. PMID:17370612

  14. Venom of the Coral Snake Micrurus clarki: Proteomic Profile, Toxicity, Immunological Cross-Neutralization, and Characterization of a Three-Finger Toxin

    PubMed Central

    Lomonte, Bruno; Sasa, Mahmood; Rey-Suárez, Paola; Bryan, Wendy; Gutiérrez, José María

    2016-01-01

    Micrurus clarki is an uncommon coral snake distributed from the Southeastern Pacific of Costa Rica to Western Colombia, for which no information on its venom could be found in the literature. Using a ‘venomics’ approach, proteins of at least nine families were identified, with a moderate predominance of three-finger toxins (3FTx; 48.2%) over phospholipase A2 (PLA2; 36.5%). Comparison of this venom profile with those of other Micrurus species suggests that it may represent a more balanced, ‘intermediate’ type within the dichotomy between 3FTx- and PLA2-predominant venoms. M. clarki venom was strongly cross-recognized and, accordingly, efficiently neutralized by an equine therapeutic antivenom against M. nigrocinctus, revealing their high antigenic similarity. Lethal activity for mice could be reproduced by a PLA2 venom fraction, but, unexpectedly, not by fractions corresponding to 3FTxs. The most abundant venom component, hereby named clarkitoxin-I, was identified as a short-chain (type I) 3FTx, devoid of lethal effect in mice, whose target remains to be defined. Its amino acid sequence of 66 residues shows high similarity with predicted sequences of venom gland transcripts described for M. fulvius, M. browni, and M. diastema. PMID:27164141

  15. Toxic trauma.

    PubMed

    Moles, T M; Baker, D J

    2001-01-01

    Hazardous materials (HAZMAT) carry many inherent dangers. Such materials are distributed widely in industrial and military sites. Toxic trauma (TT) denotes the complex of systemic and organ injury caused by toxic agents. Often, TT is associated with other injuries that also require the application of life-support techniques. Rapid onset of acute respiratory failure and consequent cardiovascular failure are of primary concern. Management of TT casualties is dependent upon the characteristics of the toxic agents involved and on the demographics surrounding the HAZMAT incident. Agents that can produce TT possess two pairs of salient characteristics: (1) causality (toxicity and latency), and (2) EMS system (persistency and transmissibility). Two characteristics of presentations are important: (1) incident presentation, and (2) casualty presentation. In addition, many of these agents complicate the processes associated with anaesthesia and must be dealt with. Failure of recognition of these factors may result in the development of respiratory distress syndromes and multiorgan system failure, or even death. PMID:11513285

  16. Digitalis toxicity

    MedlinePlus

    These are symptoms of digitalis toxicity: Confusion Irregular pulse Loss of appetite Nausea , vomiting , diarrhea Fast heartbeat Vision changes (unusual), including blind spots, blurred vision, changes in how colors look, or ...

  17. Antimony Toxicity

    PubMed Central

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically. PMID:21318007

  18. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with (177)Lu-DOTATATE.

    PubMed

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium ((177)Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with (177)Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites

  19. Nanoparticle albumin-bound paclitaxel in a patient with locally advanced breast cancer and taxane-induced skin toxicity: a case report

    PubMed Central

    2014-01-01

    Introduction Taxanes have demonstrated effectiveness in the treatment of breast cancer, the most common type of cancer in women. The toxicity profile of taxanes (including skin toxicities) induces dose adjustment, delay, or discontinuation, which prevents a sufficient dose intensity to achieve a response. Nanoparticle albumin-bound paclitaxel, a solvent-free form of paclitaxel, prevents toxicities and reduces the pharmacokinetic interferences between paclitaxel and other drugs. Case presentation We describe the case of a 55-year-old Caucasian woman with locally advanced breast cancer treated with neoadjuvant therapy who developed secondary skin toxicity due to delayed hypersensitivity to taxanes. She received Adriamycin® (doxorubicin), cyclophosphamide and docetaxel and developed toxicity that promoted treatment delay and a switch to weekly paclitaxel. After the third and fourth weeks of treatment, paclitaxel toxicities also induced treatment delay and paclitaxel was switched to nanoparticle albumin-bound paclitaxel. She completed the five planned nanoparticle albumin-bound paclitaxel cycles with acceptable tolerability (including persistent grade 2 neuropathy) and without dose delay or adjustments. Clinical response was achieved although pathological response was not good. Conclusions Nanoparticle albumin-bound paclitaxel treatment is a good option for patients with breast cancer with taxanes-related skin toxicity. This drug allows the treatment to be completed with acceptable tolerance in our case. PMID:24386978

  20. Accept or divert?

    PubMed

    Angelucci, P A

    1999-09-01

    Stretching scarce resources is more than a managerial issue. Should you accept the patient to an understaffed ICU or divert him to another facility? The intense "medical utility" controversy focuses on a situation that critical care nurses now face every day. PMID:10614370

  1. Approaches to acceptable risk

    SciTech Connect

    Whipple, C.

    1997-04-30

    Several alternative approaches to address the question {open_quotes}How safe is safe enough?{close_quotes} are reviewed and an attempt is made to apply the reasoning behind these approaches to the issue of acceptability of radiation exposures received in space. The approaches to the issue of the acceptability of technological risk described here are primarily analytical, and are drawn from examples in the management of environmental health risks. These include risk-based approaches, in which specific quantitative risk targets determine the acceptability of an activity, and cost-benefit and decision analysis, which generally focus on the estimation and evaluation of risks, benefits and costs, in a framework that balances these factors against each other. These analytical methods tend by their quantitative nature to emphasize the magnitude of risks, costs and alternatives, and to downplay other factors, especially those that are not easily expressed in quantitative terms, that affect acceptance or rejection of risk. Such other factors include the issues of risk perceptions and how and by whom risk decisions are made.

  2. 1984 Newbery Acceptance Speech.

    ERIC Educational Resources Information Center

    Cleary, Beverly

    1984-01-01

    This acceptance speech for an award honoring "Dear Mr. Henshaw," a book about feelings of a lonely child of divorce intended for eight-, nine-, and ten-year-olds, highlights children's letters to author. Changes in society that affect children, the inception of "Dear Mr. Henshaw," and children's reactions to books are highlighted. (EJS)

  3. Why was Relativity Accepted?

    NASA Astrophysics Data System (ADS)

    Brush, S. G.

    Historians of science have published many studies of the reception of Einstein's special and general theories of relativity. Based on a review of these studies, and my own research on the role of the light-bending prediction in the reception of general relativity, I discuss the role of three kinds of reasons for accepting relativity (1) empirical predictions and explanations; (2) social-psychological factors; and (3) aesthetic-mathematical factors. According to the historical studies, acceptance was a three-stage process. First, a few leading scientists adopted the special theory for aesthetic-mathematical reasons. In the second stage, their enthusiastic advocacy persuaded other scientists to work on the theory and apply it to problems currently of interest in atomic physics. The special theory was accepted by many German physicists by 1910 and had begun to attract some interest in other countries. In the third stage, the confirmation of Einstein's light-bending prediction attracted much public attention and forced all physicists to take the general theory of relativity seriously. In addition to light-bending, the explanation of the advance of Mercury's perihelion was considered strong evidence by theoretical physicists. The American astronomers who conducted successful tests of general relativity became defenders of the theory. There is little evidence that relativity was `socially constructed' but its initial acceptance was facilitated by the prestige and resources of its advocates.

  4. UGV acceptance testing

    NASA Astrophysics Data System (ADS)

    Kramer, Jeffrey A.; Murphy, Robin R.

    2006-05-01

    With over 100 models of unmanned vehicles now available for military and civilian safety, security or rescue applications, it is important to for agencies to establish acceptance testing. However, there appears to be no general guidelines for what constitutes a reasonable acceptance test. This paper describes i) a preliminary method for acceptance testing by a customer of the mechanical and electrical components of an unmanned ground vehicle system, ii) how it has been applied to a man-packable micro-robot, and iii) discusses the value of testing both to ensure that the customer has a workable system and to improve design. The test method automated the operation of the robot to repeatedly exercise all aspects and combinations of components on the robot for 6 hours. The acceptance testing process uncovered many failures consistent with those shown to occur in the field, showing that testing by the user does predict failures. The process also demonstrated that the testing by the manufacturer can provide important design data that can be used to identify, diagnose, and prevent long-term problems. Also, the structured testing environment showed that sensor systems can be used to predict errors and changes in performance, as well as uncovering unmodeled behavior in subsystems.

  5. SEDIMENT TOXICITY ASSESSMENT: COMPARISON OF STANDARD AND NEW TESTING DESIGNS

    EPA Science Inventory

    Standard methods of sediment toxicity testing are fairly well accepted; however, as with all else, evolution of these methods is inevitable. We compared a standard ASTM 10-day amphipod toxicity testing method with smaller, 48- and 96-h test methods using very toxic and reference ...

  6. Toxic Myopathies

    PubMed Central

    Pasnoor, Mamatha; Barohn, Richard J.; Dimachkie, Mazen M.

    2014-01-01

    Muscle tissue is highly sensitive to many substances. Early recognition of toxic myopathies is important, as they potentially are reversible on removal of the offending drug or toxin, with greater likelihood of complete resolution the sooner this is achieved. Clinical features range from mild muscle pain and cramps to severe weakness with rhabdomyolysis, renal failure, and even death. The pathogenic bases can be multifactorial. This article reviews some of the common toxic myopathies and their clinical presentation, histopathologic features and possible underlying cellular mechanisms. PMID:25037083

  7. Hanford Site Solid Waste Acceptance Criteria

    SciTech Connect

    MCDOWELL, A.K.; TRINER, G.C.

    2002-03-28

    DOE Order 435.1 requires that each treatment, storage, and/or disposal facility (referred to in this document as TSD unit) that manages low-level or transuranic (TRU) waste (including mixed waste and TSCA PCB waste) maintain waste acceptance criteria. These criteria must address the various requirements to operate the TSD unit in compliance with applicable safety and environmental requirements. This document sets forth the baseline criteria for acceptance of waste at TSD units operated by WMP. The criteria for each TSD unit have been established to ensure that waste accepted can be managed in a manner that is within the operating requirements of the unit, including environmental regulations, DOE Orders, permits, technical safety requirements, waste analysis plans, performance assessments, and other applicable requirements. Revisions to the acceptance criteria document require an Unreviewed Safety Question review to document that the changes are consistent with current applicable safety analysis. Acceptance criteria apply to the following TSD units: the Low-Level Burial Grounds (LLBG) including both the nonregulated portions of the LLBG and trenches 31 and 34 of the 218-W-5 Burial Ground for mixed waste disposal; Central Waste Complex (CWC); Waste Receiving and Processing (WRAP) Facility; and T-Plant facility. Waste from all generators, both from the Hanford Site and from offsite facilities, must comply with these criteria. Exceptions can be granted as provided in Section 1.6. Specific waste streams could have additional requirements based on the identified TSD pathway. These requirements are communicated in the waste specification records (WSRds) and/or waste stream profile sheet approvals. The Hanford Site manages nonradioactive waste through direct shipments to offsite contractors. The waste acceptance requirements of the offsite TSD facility must be met for these nonradioactive wastes. This document does not address the acceptance requirements of these offsite

  8. Acceptability of human risk.

    PubMed Central

    Kasperson, R E

    1983-01-01

    This paper has three objectives: to explore the nature of the problem implicit in the term "risk acceptability," to examine the possible contributions of scientific information to risk standard-setting, and to argue that societal response is best guided by considerations of process rather than formal methods of analysis. Most technological risks are not accepted but are imposed. There is also little reason to expect consensus among individuals on their tolerance of risk. Moreover, debates about risk levels are often at base debates over the adequacy of the institutions which manage the risks. Scientific information can contribute three broad types of analyses to risk-setting deliberations: contextual analysis, equity assessment, and public preference analysis. More effective risk-setting decisions will involve attention to the process used, particularly in regard to the requirements of procedural justice and democratic responsibility. PMID:6418541

  9. Age and Acceptance of Euthanasia.

    ERIC Educational Resources Information Center

    Ward, Russell A.

    1980-01-01

    Study explores relationship between age (and sex and race) and acceptance of euthanasia. Women and non-Whites were less accepting because of religiosity. Among older people less acceptance was attributable to their lesser education and greater religiosity. Results suggest that quality of life in old age affects acceptability of euthanasia. (Author)

  10. Toxic remediation

    DOEpatents

    Matthews, Stephen M.; Schonberg, Russell G.; Fadness, David R.

    1994-01-01

    What is disclosed is a novel toxic waste remediation system designed to provide on-site destruction of a wide variety of hazardous organic volatile hydrocarbons, including but not limited to halogenated and aromatic hydrocarbons in the vapor phase. This invention utilizes a detoxification plenum and radiation treatment which transforms hazardous organic compounds into non-hazardous substances.

  11. Baby-Crying Acceptance

    NASA Astrophysics Data System (ADS)

    Martins, Tiago; de Magalhães, Sérgio Tenreiro

    The baby's crying is his most important mean of communication. The crying monitoring performed by devices that have been developed doesn't ensure the complete safety of the child. It is necessary to join, to these technological resources, means of communicating the results to the responsible, which would involve the digital processing of information available from crying. The survey carried out, enabled to understand the level of adoption, in the continental territory of Portugal, of a technology that will be able to do such a digital processing. It was used the TAM as the theoretical referential. The statistical analysis showed that there is a good probability of acceptance of such a system.

  12. High acceptance recoil polarimeter

    SciTech Connect

    The HARP Collaboration

    1992-12-05

    In order to detect neutrons and protons in the 50 to 600 MeV energy range and measure their polarization, an efficient, low-noise, self-calibrating device is being designed. This detector, known as the High Acceptance Recoil Polarimeter (HARP), is based on the recoil principle of proton detection from np[r arrow]n[prime]p[prime] or pp[r arrow]p[prime]p[prime] scattering (detected particles are underlined) which intrinsically yields polarization information on the incoming particle. HARP will be commissioned to carry out experiments in 1994.

  13. Beyond toxicity

    PubMed Central

    García, Irene; Gotor, Cecilia; Romero, Luis C

    2014-01-01

    In non-cyanogenic plants, cyanide is a co-product of ethylene and camalexin biosynthesis. To maintain cyanide at non-toxic levels, Arabidopsis plants express the mitochondrial β-cyanoalanine synthase CYS-C1. CYS-C1 knockout leads to an increased level of cyanide in the roots and leaves and a severe defect in root hair morphogenesis, suggesting that cyanide acts as a signaling factor in root development. During compatible and incompatible plant-bacteria interactions, cyanide accumulation and CYS-C1 gene expression are negatively correlated. Moreover, CYS-C1 mutation increases both plant tolerance to biotrophic pathogens and their susceptibility to necrotrophic fungi, indicating that cyanide could stimulate the salicylic acid-dependent signaling pathway of the plant immune system. We hypothesize that CYS-C1 is essential for maintaining non-toxic concentrations of cyanide in the mitochondria to facilitate cyanide’s role in signaling. PMID:24398435

  14. Toxic gases.

    PubMed Central

    Matthews, G.

    1989-01-01

    An overview of the widespread use of gases and some volatile solvents in modern society is given. The usual circumstances in which undue exposure may occur are described. The most prominent symptoms and general principles of diagnosis and treatment are given and are followed by more specific information on the commoner, more toxic materials. While acute poisonings constitute the greater part of the paper, some indication of chronic disorders arising from repeated or prolonged exposure is also given. PMID:2687827

  15. Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles

    PubMed Central

    Spiroux de Vendômois, Joël; Séralini, Gilles-Eric

    2014-01-01

    Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone. PMID:24719846

  16. CADMIUM AND ENDRIN TOXICITY TO FISH IN WATERS CONTAINING MINERAL FIBERS

    EPA Science Inventory

    Taconite tailings and their component asbestiform minerals in Lake Superior water had no demonstrable effect on the chronic toxicity of cadmium to the flagfish, Jordanella floridae. Maximum acceptable toxicant concentrations determined in life cycle tests, where effects on surviv...

  17. Thallium toxicity.

    PubMed

    Galván-Arzate, S; Santamaría, A

    1998-09-30

    Thallium (T1+) is a toxic heavy metal which was accidentally discovered by Sir William Crookes in 1861 by burning the dust from a sulfuric acid industrial plant. He observed a bright green spectral band that quickly disappeared. Crookes named the new element 'Thallium' (after thallos meaning young shoot). In 1862, Lamy described the same spectral line and studied both the physical and chemical properties of this new element (Prick, J.J.G., 1979. Thallium poisoning. In: Vinkrn, P.J., Bruyn, G.W. (Eds.), Intoxication of the Nervous System, Handbook of Clinical Neurology, vol. 36. North-Holland, New York. pp. 239-278). PMID:9801025

  18. Toxic chemicals and toxic laws

    SciTech Connect

    Koshland, D.E. Jr.

    1991-08-30

    Recently there was consternation when it was discovered that a program intended to help minorities and the underprivileged in Detroit might have to be canceled. The reason was that some of the land on which new buildings were built was thought to contain toxic chemicals and therefore fell under the provisions of the Comprehensive Environmental Response, Compensation, and Liability Act (or Superfund). This collision of two valuable programs illustrates how a program originally heralded to carry out a worthwhile goal can become flawed. Since 1980, when the Superfund Act was passed by an overwhelming majority in Congress, only 34 of 1,245 identified priority sites have been cleaned up while approximately 40% of the money has been spent in trial litigation and administrative oversight. Critics, many of them within the EPA, point out that if the chemical danger level had been scientifically determined, approximately 90% of the truly important sites could have been cleaned up by now and the money wisely spent. However, the program was designed so that Congress initially did not have to raise much money or raise taxes and instead could argue that the program would not cost the taxpayer anything because it soaked the corporations. What needs to be done First, priority decisions should be taken out of the hands of nonscientists and lawyers and placed in those of scientists who are knowledgeable about toxic agents, who can identify effective targets objectively and who can establish workable priorities for removal of toxic waste. Second, a significant fraction of the money should be dedicated to research and to new programs that are more cost-effective. The purpose is to get chemical manufacturers thinking about reducing pollutants and the cost of cleanup when they plan to manufacture a chemical.

  19. Sonic boom acceptability studies

    NASA Astrophysics Data System (ADS)

    Shepherd, Kevin P.; Sullivan, Brenda M.; Leatherwood, Jack D.; McCurdy, David A.

    1992-04-01

    The determination of the magnitude of sonic boom exposure which would be acceptable to the general population requires, as a starting point, a method to assess and compare individual sonic booms. There is no consensus within the scientific and regulatory communities regarding an appropriate sonic boom assessment metric. Loudness, being a fundamental and well-understood attribute of human hearing was chosen as a means of comparing sonic booms of differing shapes and amplitudes. The figure illustrates the basic steps which yield a calculated value of loudness. Based upon the aircraft configuration and its operating conditions, the sonic boom pressure signature which reaches the ground is calculated. This pressure-time history is transformed to the frequency domain and converted into a one-third octave band spectrum. The essence of the loudness method is to account for the frequency response and integration characteristics of the auditory system. The result of the calculation procedure is a numerical description (perceived level, dB) which represents the loudness of the sonic boom waveform.

  20. Sonic boom acceptability studies

    NASA Technical Reports Server (NTRS)

    Shepherd, Kevin P.; Sullivan, Brenda M.; Leatherwood, Jack D.; Mccurdy, David A.

    1992-01-01

    The determination of the magnitude of sonic boom exposure which would be acceptable to the general population requires, as a starting point, a method to assess and compare individual sonic booms. There is no consensus within the scientific and regulatory communities regarding an appropriate sonic boom assessment metric. Loudness, being a fundamental and well-understood attribute of human hearing was chosen as a means of comparing sonic booms of differing shapes and amplitudes. The figure illustrates the basic steps which yield a calculated value of loudness. Based upon the aircraft configuration and its operating conditions, the sonic boom pressure signature which reaches the ground is calculated. This pressure-time history is transformed to the frequency domain and converted into a one-third octave band spectrum. The essence of the loudness method is to account for the frequency response and integration characteristics of the auditory system. The result of the calculation procedure is a numerical description (perceived level, dB) which represents the loudness of the sonic boom waveform.

  1. Toxic terror

    SciTech Connect

    Whelan, E.M.

    1985-01-01

    A review of toxic materials in the environment explores the evolution of public awareness of the problem, public and governmental reaction, the effort to establish standards of safe levels and danger thresholds, and the struggle to implement and enforce environmental policy. Separate chapters deal with environmental premises and scientific realities, the DDT debate and birth of environmentalism, the disaster of Love Canal, pesticides, PCBs, PBBs, formaldehyde, dioxin, air pollution, water pollution, nuclear energy and radioactive materials, acid rain, and the status of American health. The book concludes with a chapter on the need for scientific research and hard evidence to either prove or disprove the pessimism of those who warn of a threat to human health and survival.

  2. Assessing the toxic effects of ethylene glycol ethers using Quantitative Structure Toxicity Relationship models

    SciTech Connect

    Ruiz, Patricia; Mumtaz, Moiz; Gombar, Vijay

    2011-07-15

    Experimental determination of toxicity profiles consumes a great deal of time, money, and other resources. Consequently, businesses, societies, and regulators strive for reliable alternatives such as Quantitative Structure Toxicity Relationship (QSTR) models to fill gaps in toxicity profiles of compounds of concern to human health. The use of glycol ethers and their health effects have recently attracted the attention of international organizations such as the World Health Organization (WHO). The board members of Concise International Chemical Assessment Documents (CICAD) recently identified inadequate testing as well as gaps in toxicity profiles of ethylene glycol mono-n-alkyl ethers (EGEs). The CICAD board requested the ATSDR Computational Toxicology and Methods Development Laboratory to conduct QSTR assessments of certain specific toxicity endpoints for these chemicals. In order to evaluate the potential health effects of EGEs, CICAD proposed a critical QSTR analysis of the mutagenicity, carcinogenicity, and developmental effects of EGEs and other selected chemicals. We report here results of the application of QSTRs to assess rodent carcinogenicity, mutagenicity, and developmental toxicity of four EGEs: 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol and their metabolites. Neither mutagenicity nor carcinogenicity is indicated for the parent compounds, but these compounds are predicted to be developmental toxicants. The predicted toxicity effects were subjected to reverse QSTR (rQSTR) analysis to identify structural attributes that may be the main drivers of the developmental toxicity potential of these compounds.

  3. Geographical distribution and source type analysis of toxic metal emissions

    SciTech Connect

    Benjey, W.G.; Conventry, D.H.

    1992-05-01

    An interim toxic emission inventory has been developed for the conterminous United States. Seven toxic metals found in lake and coastal waters are included: arsenic, cadmium, chromium, lead, mercury, nickel and selenium. The emissions are large relative to some estimates and demonstrate the importance of metal production in toxic metal emissions. In the absence of regional inventories dedicated to toxic emissions, there is a need for improvement of emission factors and speciation profiles for use with particulate emission inventories.

  4. Illumina microRNA profiles reveal the involvement of miR397a in Citrus adaptation to long-term boron toxicity via modulating secondary cell-wall biosynthesis.

    PubMed

    Huang, Jing-Hao; Qi, Yi-Ping; Wen, Shou-Xing; Guo, Peng; Chen, Xiao-Min; Chen, Li-Song

    2016-01-01

    The mechanisms underlying tolerance to B-toxicity in plants are still controversial. Our previous studies indicated that B-toxicity is mainly limited to leaves in Citrus and that alternations of cell-wall structure in vascular bundles are involved in tolerance to B-toxicity. Here, miRNAs and their expression patterns were first identified in B-treated Citrus sinensis (tolerant) and C. grandis (intolerant) leaves via high-throughput sequencing. Candidate miRNAs were then verified with molecular and anatomical approaches. The results showed that 51 miRNAs in C. grandis and 20 miRNAs in C. sinensis were differentially expressed after B-toxic treatment. MiR395a and miR397a were the most significantly up-regulated miRNAs in B-toxic C. grandis leaves, but both were down-regulated in B-toxic C. sinensis leaves. Four auxin response factor genes and two laccase (LAC) genes were confirmed through 5'-RACE to be real targets of miR160a and miR397a, respectively. Up-regulation of LAC4 resulted in secondary deposition of cell-wall polysaccharides in vessel elements of C. sinensis, whereas down-regulation of both LAC17 and LAC4, led to poorly developed vessel elements in C. grandis. Our findings demonstrated that miR397a plays a pivotal role in woody Citrus tolerance to B-toxicity by targeting LAC17 and LAC4, both of which are responsible for secondary cell-wall synthesis. PMID:26962011

  5. Illumina microRNA profiles reveal the involvement of miR397a in Citrus adaptation to long-term boron toxicity via modulating secondary cell-wall biosynthesis

    PubMed Central

    Huang, Jing-Hao; Qi, Yi-Ping; Wen, Shou-Xing; Guo, Peng; Chen, Xiao-Min; Chen, Li-Song

    2016-01-01

    The mechanisms underlying tolerance to B-toxicity in plants are still controversial. Our previous studies indicated that B-toxicity is mainly limited to leaves in Citrus and that alternations of cell-wall structure in vascular bundles are involved in tolerance to B-toxicity. Here, miRNAs and their expression patterns were first identified in B-treated Citrus sinensis (tolerant) and C. grandis (intolerant) leaves via high-throughput sequencing. Candidate miRNAs were then verified with molecular and anatomical approaches. The results showed that 51 miRNAs in C. grandis and 20 miRNAs in C. sinensis were differentially expressed after B-toxic treatment. MiR395a and miR397a were the most significantly up-regulated miRNAs in B-toxic C. grandis leaves, but both were down-regulated in B-toxic C. sinensis leaves. Four auxin response factor genes and two laccase (LAC) genes were confirmed through 5′-RACE to be real targets of miR160a and miR397a, respectively. Up-regulation of LAC4 resulted in secondary deposition of cell-wall polysaccharides in vessel elements of C. sinensis, whereas down-regulation of both LAC17 and LAC4, led to poorly developed vessel elements in C. grandis. Our findings demonstrated that miR397a plays a pivotal role in woody Citrus tolerance to B-toxicity by targeting LAC17 and LAC4, both of which are responsible for secondary cell-wall synthesis. PMID:26962011

  6. Sediment Toxicity Identification Evaluation

    EPA Science Inventory

    Approach combining chemical manipulations and aquatic toxicity testing, generally with whole organisms, to systematically characterize, identify and confirm toxic substances causing toxicity in whole sediments and sediment interstitial waters. The approach is divided into thre...

  7. Accepters and Rejecters of Counseling.

    ERIC Educational Resources Information Center

    Rose, Harriett A.; Elton, Charles F.

    Personality differences between students who accept or reject proffered counseling assistance were investigated by comparing personality traits of 116 male students at the University of Kentucky who accepted or rejected letters of invitation to group counseling. Factor analysis of Omnibus Personality Inventory (OPI) scores to two groups of 60 and…

  8. Cone penetrometer acceptance test report

    SciTech Connect

    Boechler, G.N.

    1996-09-19

    This Acceptance Test Report (ATR) documents the results of acceptance test procedure WHC-SD-WM-ATR-151. Included in this report is a summary of the tests, the results and issues, the signature and sign- off ATP pages, and a summarized table of the specification vs. ATP section that satisfied the specification.

  9. Chronic toxicity of biphenyl to Daphnia magna Straus

    SciTech Connect

    Gersich, F.M.; Bartlett, E.A.; Murphy, P.G.; Milazzo, D.P. )

    1989-09-01

    The US Environmental Protection Agency (EPA) issued a final test rule (1985) for biphenyl on the authority of Section 4(a) of the Toxic Substances Control Act (TSCA). Contained within this rule was the requirement for generating chronic daphnid toxicity data for biphenyl. Biphenyl is used primarily to produce dye carriers, heat-transfer fluids and alkylated biphenyls. The acute toxicity of biphenyl to Daphnia magna has been reported. The 48-hr LC50 values were 4.7 and 2.1 mg/L, respectively. To date, the chronic toxicity of biphenyl to fish and aquatic invertebrates has not been investigated. The objective of this study was to determine the chronic toxicity of biphenyl to D. magna. The daphnid chronic toxicity test is designed to estimate the maximum acceptable toxicant concentration (MATC). The MATC is defined as the concentration falling between the highest concentration showing no effect and the next higher concentration showing a toxic effect when compared to the controls.

  10. Health and Environmental Effects Profile for dinitrocresols

    SciTech Connect

    Not Available

    1986-07-01

    The Health and Environmental Effects Profile for Dinitrocresols was prepared to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Dinitrocresols has been determined to be a systemic toxicant. An Acceptable Daily Intake (ADI), defined as the amount of a chemical to which humans can be exposed on a daily basis over an extended period of time (usually a lifetime) without suffering a deleterious effect, for 4,6-dinitrocresol is 0.001 mg/kg/day for inhalation exposure. The Reportable Quantity (RQ) value of 1, 10, 100, 1000 or 5000 pounds is used to determine the quantity of a hazardous substance for which notification is required in the event of a release as specified by CERCLA based on chronic toxicity. The RQ value for 4,6-dinitro-o-cresol is 100. Existing data are insufficient to determine an RQ value for 2,6-dinitro-p-cresol.

  11. Health and Environmental Effects Profile for chloroacetaldehyde

    SciTech Connect

    Not Available

    1986-06-01

    The Health and Environmental Effects Profile for Chloroacetaldehyde was prepared to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Quantitative estimates are presented provided sufficient data are available. Chloroacetaldehyde has been determined to be a systemic toxicant. An Acceptable Daily Intake (ADI), defined as the amount of a chemical to which humans can be exposed on a daily basis over an extended period of time (usually a lifetime) without suffering a deleterious effect, for chloroacetaldehyde is 0.007 mg/kg/day for oral exposure. The Reportable Quantity (RQ) value of 1, 10, 100, 1000 or 5000 pounds is used to determine the quantity of a hazardous substance for which notification is required in the event of a release as specified by CERCLA based on chronic toxicity. Existing data are insufficient to determine an RQ value.

  12. AQUATIC FATE AND TRANSPORT MODELING TECHNIQUES FOR PREDICTING ENVIRONMENTAL EXPOSURE TO ORGANIC PESTICIDES AND OTHER TOXICANTS - A COMPARATIVE STUDY

    EPA Science Inventory

    Exposure assessment enhanced by mathematical modeling has become an accepted technique for evaluating the environmental risk associated with the release of toxic substances into various environmental media. Mathematical models for analyzing the behavior of toxic substances in riv...

  13. High-Throughput Cell Toxicity Assays.

    PubMed

    Murray, David; McWilliams, Lisa; Wigglesworth, Mark

    2016-01-01

    Understanding compound-driven cell toxicity is vitally important for all drug discovery approaches. With high-throughput screening (HTS) being the key strategy to find hit and lead compounds for drug discovery projects in the pharmaceutical industry [1], an understanding of the cell toxicity profile of hit molecules from HTS activities is fundamentally important. Recently, there has been a resurgence of interest in phenotypic drug discovery and these cell-based assays are now being run in HTS labs on ever increasing numbers of compounds. As the use of cell assays increases the ability to measure toxicity of compounds on a large scale becomes increasingly important to ensure that false hits are not progressed and that compounds do not carry forward a toxic liability that may cause them to fail at later stages of a project. Here we describe methods employed in the AstraZeneca HTS laboratory to carry out very large scale cell toxicity screening. PMID:27317000

  14. Accepted scientific research works (abstracts).

    PubMed

    2014-01-01

    These are the 39 accepted abstracts for IAYT's Symposium on Yoga Research (SYR) September 24-24, 2014 at the Kripalu Center for Yoga & Health and published in the Final Program Guide and Abstracts. PMID:25645134

  15. L-286 Acceptance Test Record

    SciTech Connect

    HARMON, B.C.

    2000-01-14

    This document provides a detailed account of how the acceptance testing was conducted for Project L-286, ''200E Area Sanitary Water Plant Effluent Stream Reduction''. The testing of the L-286 instrumentation system was conducted under the direct supervision

  16. New approaches in the derivation of acceptable daily intake (ADI)

    SciTech Connect

    Dourson, M.L.

    1986-01-01

    Current methods for estimating human health risks from exposure to threshold-acting toxicants in water or food, such as those established by the U.S. EPA, the FDA, the NAS, the WHO and the FAO, consider only chronic or lifetime exposure to individual chemicals. These methods generally estimate a single, constant daily intake rate which is low enough to be considered safe or acceptable. The intake rate is termed the acceptable daily intake (ADI). Two problems with the approach have been recognized. The first problem is that the method does not readily account for the number of animals used to determine the appropriate 'no-observed-effect-level' (NOEL). The second problem with the current approach is that the slope of the dose-response curve of the critical toxic effect is generally ignored in estimating the ADI. The report illustrates both a revised approach to estimate ADIs with all toxicity data which includes methods for partial lifetime assessment, and novel methods for ADI estimation with quantal or continuous toxicity data. The latter method addresses to a degree the common problems with the current approach.

  17. Thermal stress and toxicity.

    PubMed

    Gordon, Christopher J; Johnstone, Andrew F M; Aydin, Cenk

    2014-07-01

    Elevating ambient temperature above thermoneutrality exacerbates toxicity of most air pollutants, insecticides, and other toxic chemicals. On the other hand, safety and toxicity testing of toxicants and drugs is usually performed in mice and rats maintained at sub-thermoneutral temperatures of ~22∘C. When exposed to chemical toxicants under these relatively cool conditions, rodents typically undergo a regulated hypothermic response, characterized by preference for cooler ambient temperatures and controlled reduction in core temperature. Reducing core temperature delays the clearance of most toxicants from the body; however, a mild hypothermia also improves recovery and survival from the toxicant. Raising ambient temperature to thermoneutrality and above increases the rate of clearance of the toxicant but also exacerbates toxicity. Furthermore, heat stress combined with work or exercise is likely to worsen toxicity. Body temperature of large mammals, including humans, does not decrease as much in response to exposure to a toxicant. However, heat stress can nonetheless worsen toxic outcome in humans through a variety of mechanisms. For example, heat-induced sweating and elevation in skin blood flow accelerates uptake of some insecticides. Epidemiological studies suggest that thermal stress may exacerbate the toxicity of airborne pollutants such as ozone and particulate matter. Overall, translating results of studies in rodents to that of humans is a formidable task attributed in part to the interspecies differences in thermoregulatory response to the toxicants and to thermal stress. PMID:24944028

  18. Idaho CERCLA Disposal Facility Complex Waste Acceptance Criteria

    SciTech Connect

    W. Mahlon Heileson

    2006-10-01

    The Idaho Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) Disposal Facility (ICDF) has been designed to accept CERCLA waste generated within the Idaho National Laboratory. Hazardous, mixed, low-level, and Toxic Substance Control Act waste will be accepted for disposal at the ICDF. The purpose of this document is to provide criteria for the quantities of radioactive and/or hazardous constituents allowable in waste streams designated for disposal at ICDF. This ICDF Complex Waste Acceptance Criteria is divided into four section: (1) ICDF Complex; (2) Landfill; (3) Evaporation Pond: and (4) Staging, Storage, Sizing, and Treatment Facility (SSSTF). The ICDF Complex section contains the compliance details, which are the same for all areas of the ICDF. Corresponding sections contain details specific to the landfill, evaporation pond, and the SSSTF. This document specifies chemical and radiological constituent acceptance criteria for waste that will be disposed of at ICDF. Compliance with the requirements of this document ensures protection of human health and the environment, including the Snake River Plain Aquifer. Waste placed in the ICDF landfill and evaporation pond must not cause groundwater in the Snake River Plain Aquifer to exceed maximum contaminant levels, a hazard index of 1, or 10-4 cumulative risk levels. The defined waste acceptance criteria concentrations are compared to the design inventory concentrations. The purpose of this comparison is to show that there is an acceptable uncertainty margin based on the actual constituent concentrations anticipated for disposal at the ICDF. Implementation of this Waste Acceptance Criteria document will ensure compliance with the Final Report of Decision for the Idaho Nuclear Technology and Engineering Center, Operable Unit 3-13. For waste to be received, it must meet the waste acceptance criteria for the specific disposal/treatment unit (on-Site or off-Site) for which it is destined.

  19. Defining acceptable conditions in wilderness

    NASA Astrophysics Data System (ADS)

    Roggenbuck, J. W.; Williams, D. R.; Watson, A. E.

    1993-03-01

    The limits of acceptable change (LAC) planning framework recognizes that forest managers must decide what indicators of wilderness conditions best represent resource naturalness and high-quality visitor experiences and how much change from the pristine is acceptable for each indicator. Visitor opinions on the aspects of the wilderness that have great impact on their experience can provide valuable input to selection of indicators. Cohutta, Georgia; Caney Creek, Arkansas; Upland Island, Texas; and Rattlesnake, Montana, wilderness visitors have high shared agreement that littering and damage to trees in campsites, noise, and seeing wildlife are very important influences on wilderness experiences. Camping within sight or sound of other people influences experience quality more than do encounters on the trails. Visitors’ standards of acceptable conditions within wilderness vary considerably, suggesting a potential need to manage different zones within wilderness for different clientele groups and experiences. Standards across wildernesses, however, are remarkably similar.

  20. From requirements to acceptance tests

    NASA Technical Reports Server (NTRS)

    Baize, Lionel; Pasquier, Helene

    1993-01-01

    From user requirements definition to accepted software system, the software project management wants to be sure that the system will meet the requirements. For the development of a telecommunication satellites Control Centre, C.N.E.S. has used new rules to make the use of tracing matrix easier. From Requirements to Acceptance Tests, each item of a document must have an identifier. A unique matrix traces the system and allows the tracking of the consequences of a change in the requirements. A tool has been developed, to import documents into a relational data base. Each record of the data base corresponds to an item of a document, the access key is the item identifier. Tracing matrix is also processed, providing automatically links between the different documents. It enables the reading on the same screen of traced items. For example one can read simultaneously the User Requirements items, the corresponding Software Requirements items and the Acceptance Tests.

  1. Health and Environmental Effects Profile for maleic anhydride

    SciTech Connect

    Not Available

    1986-07-01

    The Health and Environmental Effects Profile for maleic anhydride was prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained from Agency program office files were evaluated as they pertained to potential human-health, aquatic-life, and environmental effects of hazardous-waste constituents. Maleic anhydride has been determined to be a systemic toxicant. An Acceptable Daily Intake (ADI), for maleic anhydride is 0.10 mg/kg/day for oral exposure. The Reportable Quantity (RQ) value for maleic anhydride is 100.

  2. Health and Environmental Effects Profile for methyl bromide

    SciTech Connect

    Not Available

    1986-06-01

    The Health and Environmental Effects Profile for methyl bromide was prepared to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained from Agency program office files were evaluated as they pertained to potential human health, aquatic life, and environmental effects. Quantitative estimates are presented provided sufficient data are available. Methyl bromide has been determined to be a systemic toxicant. An Acceptable Daily Intake (ADI), for methyl bromide is 0.0014 mg/kg/day for oral exposure. The Reportable Quantity (RQ) value for methyl bromide is 100.

  3. Virtual Embryo: Systems Modeling in Developmental Toxicity

    EPA Science Inventory

    High-throughput and high-content screening (HTS-HCS) studies are providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential toxicity. EPA’s ToxCast™ project, and the broader Tox21 consortium, in addition t...

  4. The MAGNEX large acceptance spectrometer

    SciTech Connect

    Cavallaro, M.; Cappuzzello, F.; Cunsolo, A.; Carbone, D.; Foti, A.

    2010-03-01

    The main features of the MAGNEX large acceptance magnetic spectrometer are described. It has a quadrupole + dipole layout and a hybrid detector located at the focal plane. The aberrations due to the large angular (50 msr) and momentum (+- 13%) acceptance are reduced by an accurate hardware design and then compensated by an innovative software ray-reconstruction technique. The obtained resolution in energy, angle and mass are presented in the paper. MAGNEX has been used up to now for different experiments in nuclear physics and astrophysics confirming to be a multipurpose device.

  5. Toxicity and clinical tolerance of lonidamine.

    PubMed

    Robustelli della Cuna, G; Pedrazzoli, P

    1991-04-01

    The new anticancer agent lonidamine has been recently revisited for the treatment of various solid tumors, due to its peculiar and unusual mechanism of action (ie, interference with energy metabolism of tumor cells, morphologically displayed by the appearance of "condensed mitochondria"). First generation trials have in fact demonstrated therapeutic activity and an unusual toxicity profile. Lonidamine is devoid of conventional side effects induced by antiproliferative agents (ie, myelosuppression, stomatitis, cystitis, alopecia, renal, hepatic, and cardiac toxicity). No serious or life-threatening adverse reactions have been recorded even over long term treatment periods. Given as a single agent (in daily doses ranging between 300 and 900 mg) lonidamine induces the following side effects: myalgia, testicular pain, asthenia, ototoxicity, nausea and vomiting, gastric pain, and drowsiness. Hyperesthesia and photophobia have also been reported. In combination with radiotherapy (in oral daily doses ranging between 300 and 450 mg) lonidamine was well tolerated, without any reported evidence of additional toxicity. When associated with cytotoxic agents no enhanced toxicity was observed. In particular, myelosuppression and other conventional nonhematological adverse reactions were never greater than would be expected with chemotherapy alone. The same applies to toxicity and tolerance of lonidamine when used concurrently with hypertermia. The data collected from large series of cancer patients treated with this new agent show that lonidamine is a safe drug whether used alone or in combination with other effective anticancer treatments. The reported therapeutic efficacy and the peculiar toxic profile make lonidamine an interesting new drug for future clinical trials. PMID:2031192

  6. Toxicity and repellency to rats of actidione

    USGS Publications Warehouse

    Traub, R.; DeWitt, J.B.; Welch, J.F.; Newman, D.

    1950-01-01

    The antibiotic actidione was found to be highly repellent to laboratory rats and to significantly reduce gnawing attacks upon treated paperboards. Rats refused to accept food or water containing this material even under conditions of acute starvation and died of starvation and thirst,rather than accept water containing l.0 mg. of actidione per liter. The compound is highly toxic to .rats with the minimum .lethal dose by oral administration being approximately l.0 mg./Kg body weight. Paperboard treated with the compound resisted gnawing attacks by specially trained and motivated rats for periods of two hundred hours, although similar .untreated boards were pierced within thirty-to sixty minutes.

  7. TOXICS RELEASE INVENTORY (TRI)

    EPA Science Inventory

    The Toxics Release Inventory (TRI) site is designed to provide information on toxic chemical releases including collected data, guidance documents, program planning, background, history, and, program contacts, among other things. The data included in this homepage have been submi...

  8. The minipig as a new model for the evaluation of doxorubicin-induced chronic toxicity.

    PubMed

    Manno, Rosa Anna; Grassetti, Andrea; Oberto, Germano; Nyska, Abraham; Ramot, Yuval

    2016-08-01

    Doxorubicin can cause life-threatening toxic effects in several organs, with cardiotoxicity being the major concern. Although a large number of animal models have been utilized to study doxorubicin toxicity, several restrictions limit their use. Since the Göttingen minipig is an accepted species for non-clinical safety assessment and translation to man, we aimed at exploring its use as a non-rodent animal model for safety assessment and regulatory toxicity studies using doxorubicin. Three groups of three males and three females adult Göttingen minipigs received 1.5 mg kg(-1) , 3/2.3 mg kg(-1) or vehicle at intervals of 3 weeks for 7 cycles. Doxorubicin treatment resulted in a dose-related decrease in the erythrocytes, hemoglobin and hematocrit count, accompanied by leukopenia and thrombocytopenia. Bone marrow smears revealed dose-related hypocellularity. Urea and creatinine levels were elevated in treated animals, associated with proteinuria and hematuria. Histopathological evaluation detected nephropathy and atrophy of hematopoietic tissues/organs, mucosa of the intestinal tract and male genital tract. Cardiac lesions including chronic inflammation, endocardial hyperplasia, hemorrhage and myxomatous changes were evident in hematoxylin and eosin stains, and evaluation of semi-thin sections showed the presence of dose-related vacuolation in the atrial and ventricular cardiomyocytes. Cardiac troponin levels were increased in the high-dose group, but there was no direct correlation to the severity of the histopathological lesions. This study confirms that the Göttingen minipig has a comparable toxicity profile to humans and considering its anatomical, physiological, genetic and biochemical resemblance to humans, it should be considered as the non-rodent species of choice for studies on doxorubicin toxicity. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26614124

  9. Nitrogen trailer acceptance test report

    SciTech Connect

    Kostelnik, A.J.

    1996-02-12

    This Acceptance Test Report documents compliance with the requirements of specification WHC-S-0249. The equipment was tested according to WHC-SD-WM-ATP-108 Rev.0. The equipment being tested is a portable contained nitrogen supply. The test was conducted at Norco`s facility.

  10. Helping Our Children Accept Themselves.

    ERIC Educational Resources Information Center

    Gamble, Mae

    1984-01-01

    Parents of a child with muscular dystrophy recount their reactions to learning of the diagnosis, their gradual acceptance, and their son's resistance, which was gradually lessened when he was provided with more information and treated more normally as a member of the family. (CL)

  11. Acceptability of Treatments for Plagiarism

    ERIC Educational Resources Information Center

    Carter, Stacy L.; Punyanunt-Carter, Narissra Maria

    2007-01-01

    This study focused on various treatments for addressing incidents of plagiarism by college students. College students rated the acceptability of different responses by college faculty to a case description of a college student who engaged in plagiarism. The findings revealed that students found some methods of addressing this problem behavior by…

  12. Euthanasia Acceptance: An Attitudinal Inquiry.

    ERIC Educational Resources Information Center

    Klopfer, Fredrick J.; Price, William F.

    The study presented was conducted to examine potential relationships between attitudes regarding the dying process, including acceptance of euthanasia, and other attitudinal or demographic attributes. The data of the survey was comprised of responses given by 331 respondents to a door-to-door interview. Results are discussed in terms of preferred…

  13. Social acceptability of phytoremediation: The role of risk and values.

    PubMed

    Weir, Ellen; Doty, Sharon

    2016-10-01

    A former gas production site that was converted to a public park was chosen as the research location for the present study. Some of the contaminants at the site have been remediated; however, much of the soil is still contaminated with polycyclic aromatic hydrocarbons (PAHs). PAHs are toxic pollutants that have been shown to have numerous negative health effects. The primary form of remediation at the site has been capping, which is usually considered a temporary remediation strategy since it does not remove contaminants from the site but simply covers them, and this requires repeated re-capping efforts. Endophyte-assisted phytoremediation using willow shrubs is an alternative remediation strategy that could improve soil quality and permanently reduce contaminant levels in the soil. The goal of the present study was to explore the social acceptability of utilizing phytoremediation strategies. Surveys were used to explore public perceptions of the park and of using phytoremediation to clean up existing contamination. Results indicated a high level of social acceptability of phytoremediation at the park. Additionally, ecocentrism was shown to be a significant predictor of phytoremediation acceptability. Risk and anthropocentrism were not significant predictors of acceptability. Results suggest that messages intended to encourage the use and acceptability of phytoremediation should focus on the environmental benefits of phytoremediation. PMID:27167719

  14. Automated Test Systems for Toxic Vapor Detectors

    NASA Technical Reports Server (NTRS)

    Mattson, C. B.; Hammond, T. A.; Schwindt, C. J.

    1997-01-01

    The NASA Toxic Vapor Detection Laboratory (TVDL) at the Kennedy Space Center (KSC), Florida, has been using Personal Computer based Data Acquisition and Control Systems (PCDAS) for about nine years. These systems control the generation of toxic vapors of known concentrations under controlled conditions of temperature and humidity. The PCDAS also logs the test conditions and the test article responses in data files for analysis by standard spreadsheets or custom programs. The PCDAS was originally developed to perform standardized qualification and acceptance tests in a search for a commercial off-the-shelf (COTS) toxic vapor detector to replace the hydrazine detectors for the Space Shuttle launch pad. It has since become standard test equipment for the TVDL and is indispensable in producing calibration standards for the new hydrazine monitors at the 10 part per billion (ppb) level. The standard TVDL PCDAS can control two toxic vapor generators (TVG's) with three channels each and two flow/temperature/humidity (FIFH) controllers and it can record data from up to six toxic vapor detectors (TVD's) under test and can deliver flows from 5 to 50 liters per minute (L/m) at temperatures from near zero to 50 degrees Celsius (C) using an environmental chamber to maintain the sample temperature. The concentration range for toxic vapors depends on the permeation source installed in the TVG. The PCDAS can provide closed loop control of temperature and humidity to two sample vessels, typically one for zero gas and one for the standard gas. This is required at very low toxic vapor concentrations to minimize the time required to passivate the sample delivery system. Recently, there have been several requests for information about the PCDAS by other laboratories with similar needs, both on and off KSC. The purpose of this paper is to inform the toxic vapor detection community of the current status and planned upgrades to the automated testing of toxic vapor detectors at the Kennedy

  15. Automated Test Systems for Toxic Vapor Detectors

    NASA Technical Reports Server (NTRS)

    Mattson, C. B.; Hammond, T. A.; Schwindt, C. J.

    1997-01-01

    The NASA Toxic Vapor Detection Laboratory (TVDL) at the Kennedy Space Center (KSC), Florida, has been using Personal Computer based Data Acquisition and Control Systems (PCDAS) for about nine years. These systems control the generation of toxic vapors of known concentrations under controlled conditions of temperature and humidity. The PCDAS also logs the test conditions and the test article responses in data files for analysis by standard spreadsheets or custom programs. The PCDAS was originally developed to perform standardized qualification and acceptance tests in a search for a commercial off-the-shelf (COTS) toxic vapor detector to replace the hydrazine detectors for the Space Shuttle launch pad. It has since become standard test equipment for the TVDL and is indispensable in producing calibration standards for the new hydrazine monitors at the 10 part per billion (ppb) level. The standard TVDL PCDAS can control two toxic vapor generators (TVG's) with three channels each and two flow/ temperature / humidity (FTH) controllers and it can record data from up to six toxic vapor detectors (TVD's) under test and can deliver flows from 5 to 50 liters per minute (L/m) at temperatures from near zero to 50 degrees Celsius (C) using an environmental chamber to maintain the sample temperature. The concentration range for toxic vapors depends on the permeation source installed in the TVG. The PCDAS can provide closed loop control of temperature and humidity to two sample vessels, typically one for zero gas and one for the standard gas. This is required at very low toxic vapor concentrations to minimize the time required to passivate the sample delivery system. Recently, there have been several requests for information about the PCDAS by other laboratories with similar needs, both on and off KSC. The purpose of this paper is to inform the toxic vapor detection community of the current status and planned upgrades to the automated testing of toxic vapor detectors at the

  16. Practical Differential Profiling

    SciTech Connect

    Schulz, M; De Supinski, B R

    2007-02-04

    Comparing performance profiles from two runs is an essential performance analysis step that users routinely perform. In this work we present eGprof, a tool that facilitates these comparisons through differential profiling inside gprof. We chose this approach, rather than designing a new tool, since gprof is one of the few performance analysis tools accepted and used by a large community of users. eGprof allows users to 'subtract' two performance profiles directly. It also includes callgraph visualization to highlight the differences in graphical form. Along with the design of this tool, we present several case studies that show how eGprof can be used to find and to study the differences of two application executions quickly and hence can aid the user in this most common step in performance analysis. We do this without requiring major changes on the side of the user, the most important factor in guaranteeing the adoption of our tool by code teams.

  17. How Toxic Is It?

    ERIC Educational Resources Information Center

    Crellin, John R.

    1989-01-01

    Discusses the relative danger from toxicity of some typical chemicals. Notes that some materials in solutions have low toxicity, but in dust form have high toxicity. Suggests that more chemical compounds should be treated as the dangerous compounds they are. Lists common compounds found in the lab. (MVL)

  18. Toxic Hazards Research Unit

    NASA Technical Reports Server (NTRS)

    Macewen, J. D.; Vernot, E. H.

    1971-01-01

    The activities of the Toxic Hazards Research Unit (THRU) for the period of June 1970 through May 1971 reviewed. Modification of the animal exposure facilities primarily for improved human safety but also for experimental integrity and continuity are discussed. Acute toxicity experiments were conducted on hydrogen fluoride (HF), hydrogen chloride (HCl), nitrogen dioxide (NO2), and hydrogen cyanide (HCN) both singly and in combination with carbon dioxide (CO). Additional acute toxicity experiments were conducted on oxygen difluoride (OF2) and chlorine pentafluoride (ClF5). Subacute toxicity studies were conducted on methylisobutylketone and dichloromethane (methylene dichloride). The interim results of further chronic toxicity experiments on monomethylhydrazine (MMH) are also described.

  19. Relative toxicity of materials in fire situations

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Cumming, H. J.; Casey, C. J.

    1978-01-01

    The results of toxicity testing of additional materials is presented. Relative toxicity data on polymers by generic type are presented and include wood, polyurethane flexible foam, polyvinyl chloride (PVC), acrylonitrile/butadiene/styrene (ABS), and polyisoprene (natural rubber). A second table gives relative toxicity data on fibers and fabrics including wool, nylon, rayon, polyester, and aromatic polyamide. Sulfur-containing materials seemed to exhibit the shortest times to death of laboratory animals. Some chlorine-containing polymers tended to exhibit shortest time to death also while some halogen-containing polymers gave the shortest time to incapacitation. Among fibers and fabrics, wool, silk, and polyester exhibited the shortest times to incapacitation and times to death. Difficulty in restricting generally accepted materials is discussed and attention is given to other factors important in comparing materials, such as backcoatings and relative weights.

  20. Acceptability of reactors in space

    SciTech Connect

    Buden, D.

    1981-04-01

    Reactors are the key to our future expansion into space. However, there has been some confusion in the public as to whether they are a safe and acceptable technology for use in space. The answer to these questions is explored. The US position is that when reactors are the preferred technical choice, that they can be used safely. In fact, it dies not appear that reactors add measurably to the risk associated with the Space Transportation System.

  1. Acceptability of reactors in space

    SciTech Connect

    Buden, D.

    1981-01-01

    Reactors are the key to our future expansion into space. However, there has been some confusion in the public as to whether they are a safe and acceptable technology for use in space. The answer to these questions is explored. The US position is that when reactors are the preferred technical choice, that they can be used safely. In fact, it does not appear that reactors add measurably to the risk associated with the Space Transportation System.

  2. Reactor tank UT acceptance criteria

    SciTech Connect

    Daugherty, W.L.

    1990-01-30

    The SRS reactor tanks are constructed of type 304 stainless steel, with 0.5 inch thick walls. An ultrasonic (UT) in-service inspection program has been developed for examination of these tanks, in accordance with the ISI Plan for the Savannah River Production Reactors Process Water System (DPSTM-88-100-1). Prior to initiation of these inspections, criteria for the disposition of any indications that might be found are required. A working group has been formed to review available information on the SRS reactor tanks and develop acceptance criteria. This working group includes nationally recognized experts in the nuclear industry. The working group has met three times and produced three documents describing the proposed acceptance criteria, the technical basis for the criteria and a proposed initial sampling plan. This report transmits these three documents, which were prepared in accordance with the technical task plan and quality assurance plan for this task, task 88-001-A- 1. In addition, this report summarizes the acceptance criteria and proposed sampling plan, and provides further interpretation of the intent of these three documents where necessary.

  3. High-dose paclitaxel in combination with doxorubicin, cyclophosphamide and peripheral blood progenitor cell rescue in patients with high-risk primary and responding metastatic breast carcinoma: toxicity profile, relationship to paclitaxel pharmacokinetics and short-term outcome

    PubMed Central

    Somlo, G; Doroshow, J H; Synold, T; Longmate, J; Reardon, D; Chow, W; Forman, S J; Leong, L A; Margolin, K A; Jr, R J Morgan; Raschko, J W; Shibata, S I; Tetef, M L; Yen, Y; Kogut, N; Schriber, J; Alvarnas, J

    2001-01-01

    We assessed the feasibility and pharmacokinetics of high-dose infusional paclitaxel in combination with doxorubicin, cyclophosphamide, and peripheral blood progenitor cell rescue. Between October 1995 and June 1998, 63 patients with high-risk primary [stage II with ≥ 10 axillary nodes involved, stage IIIA or stage IIIB inflammatory carcinoma (n = 53)] or with stage IV responsive breast cancer (n = 10) received paclitaxel 150–775 mg/m2infused over 24 hours, doxorubicin 165 mg/m2as a continuous infusion over 96 hours, and cyclophosphamide 100 mg kg–1. There were no treatment-related deaths. Dose-limiting toxicity was reversible, predominantly sensory neuropathy following administration of paclitaxel at the 775 mg/m2dose level. Paclitaxel pharmacokinetics were non-linear at higher dose levels; higher paclitaxel dose level, AUC, and peak concentrations were associated with increased incidence of paraesthesias. No correlation between stomatitis, haematopoietic toxicities, and paclitaxel dose or pharmacokinetics was found. Kaplan–Meier estimates of 30-month event-free and overall survival for patients with primary breast carcinoma are 65% (95% CI; 51–83%) and 77% (95% CI; 64–93%). Paclitaxel up to 725 mg/m2infused over 24 hours in combination with with doxorubicin 165 mg/m2and cyclophosphamide 100 mg kg–1is tolerable. A randomized study testing this regimen against high-dose carboplatin, thiotepa and cyclophosphamide (STAMP V) is currently ongoing. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11401310

  4. Big Data in Chemical Toxicity Research: The Use of High-Throughput Screening Assays To Identify Potential Toxicants

    PubMed Central

    2015-01-01

    High-throughput screening (HTS) assays that measure the in vitro toxicity of environmental compounds have been widely applied as an alternative to in vivo animal tests of chemical toxicity. Current HTS studies provide the community with rich toxicology information that has the potential to be integrated into toxicity research. The available in vitro toxicity data is updated daily in structured formats (e.g., deposited into PubChem and other data-sharing web portals) or in an unstructured way (papers, laboratory reports, toxicity Web site updates, etc.). The information derived from the current toxicity data is so large and complex that it becomes difficult to process using available database management tools or traditional data processing applications. For this reason, it is necessary to develop a big data approach when conducting modern chemical toxicity research. In vitro data for a compound, obtained from meaningful bioassays, can be viewed as a response profile that gives detailed information about the compound’s ability to affect relevant biological proteins/receptors. This information is critical for the evaluation of complex bioactivities (e.g., animal toxicities) and grows rapidly as big data in toxicology communities. This review focuses mainly on the existing structured in vitro data (e.g., PubChem data sets) as response profiles for compounds of environmental interest (e.g., potential human/animal toxicants). Potential modeling and mining tools to use the current big data pool in chemical toxicity research are also described. PMID:25195622

  5. Big data in chemical toxicity research: the use of high-throughput screening assays to identify potential toxicants.

    PubMed

    Zhu, Hao; Zhang, Jun; Kim, Marlene T; Boison, Abena; Sedykh, Alexander; Moran, Kimberlee

    2014-10-20

    High-throughput screening (HTS) assays that measure the in vitro toxicity of environmental compounds have been widely applied as an alternative to in vivo animal tests of chemical toxicity. Current HTS studies provide the community with rich toxicology information that has the potential to be integrated into toxicity research. The available in vitro toxicity data is updated daily in structured formats (e.g., deposited into PubChem and other data-sharing web portals) or in an unstructured way (papers, laboratory reports, toxicity Web site updates, etc.). The information derived from the current toxicity data is so large and complex that it becomes difficult to process using available database management tools or traditional data processing applications. For this reason, it is necessary to develop a big data approach when conducting modern chemical toxicity research. In vitro data for a compound, obtained from meaningful bioassays, can be viewed as a response profile that gives detailed information about the compound's ability to affect relevant biological proteins/receptors. This information is critical for the evaluation of complex bioactivities (e.g., animal toxicities) and grows rapidly as big data in toxicology communities. This review focuses mainly on the existing structured in vitro data (e.g., PubChem data sets) as response profiles for compounds of environmental interest (e.g., potential human/animal toxicants). Potential modeling and mining tools to use the current big data pool in chemical toxicity research are also described. PMID:25195622

  6. 12 CFR 7.1007 - Acceptances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Acceptances. 7.1007 Section 7.1007 Banks and... § 7.1007 Acceptances. A national bank is not limited in the character of acceptances it may make in financing credit transactions. Bankers' acceptances may be used for such purpose, since the making...

  7. 12 CFR 7.1007 - Acceptances.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 1 2011-01-01 2011-01-01 false Acceptances. 7.1007 Section 7.1007 Banks and... § 7.1007 Acceptances. A national bank is not limited in the character of acceptances it may make in financing credit transactions. Bankers' acceptances may be used for such purpose, since the making...

  8. 21 CFR 820.86 - Acceptance status.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Acceptance status. 820.86 Section 820.86 Food and... QUALITY SYSTEM REGULATION Acceptance Activities § 820.86 Acceptance status. Each manufacturer shall identify by suitable means the acceptance status of product, to indicate the conformance or...

  9. 12 CFR 615.5550 - Bankers' acceptances.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Bankers' acceptances. 615.5550 Section 615.5550... POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Bankers' Acceptances § 615.5550 Bankers' acceptances. Banks for cooperatives may rediscount with other purchasers the acceptances they have created. The bank...

  10. 48 CFR 245.606-3 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Acceptance. 245.606-3... Contractor Inventory 245.606-3 Acceptance. (a) If the schedules are acceptable, the plant clearance officer shall, within 15 days, complete and send the contractor a DD Form 1637, Notice of Acceptance...

  11. 48 CFR 12.402 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Acceptance. 12.402 Section... Acceptance. (a) The acceptance paragraph in 52.212-4 is based upon the assumption that the Government will rely on the contractor's assurances that the commercial item tendered for acceptance conforms to...

  12. 21 CFR 820.86 - Acceptance status.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Acceptance status. 820.86 Section 820.86 Food and... QUALITY SYSTEM REGULATION Acceptance Activities § 820.86 Acceptance status. Each manufacturer shall identify by suitable means the acceptance status of product, to indicate the conformance or...

  13. 12 CFR 615.5550 - Bankers' acceptances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Bankers' acceptances. 615.5550 Section 615.5550... POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Bankers' Acceptances § 615.5550 Bankers' acceptances. Banks for cooperatives may rediscount with other purchasers the acceptances they have created. The bank...

  14. 48 CFR 12.402 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Acceptance. 12.402 Section... Acceptance. (a) The acceptance paragraph in 52.212-4 is based upon the assumption that the Government will rely on the contractor's assurances that the commercial item tendered for acceptance conforms to...

  15. Learning Style Profile: Examiner's Manual.

    ERIC Educational Resources Information Center

    Keefe, James W.; Monk, John S.

    This examiner's manual accompanies the Learning Style Profile (LSP), which measures cognitive skills as well as affective and environmental preferences. Charles Letteri's General Operations Model was accepted as the prototype for relating learning styles to cognitive information processing. The LSP was developed from 1983 to 1986; several versions…

  16. VIRTUAL EMBRYO: SYSTEMS MODELING IN DEVELOPMENTAL TOXICITY - Symposium: SOT 2012

    EPA Science Inventory

    High-throughput screening (HTS) studies are providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential toxicity. Chemical profiling in ToxCast covered 965 drugs-chemicals in over 500 diverse assays testing...

  17. Possible toxic metal exposure of prehistoric bronze workers.

    PubMed Central

    Harper, M

    1987-01-01

    An attempt has been made to assess the possible occupational exposure to arsenic, lead, and mercury during the Bronze Age. Archaeological, metallurgical, and historical evidence is combined to form a picture of the potential toxic hazards. In the case of arsenic a definite picture emerges of the effect of toxicity as a useful material is abandoned for health reasons on discovery of an acceptable alternative. Images PMID:3314977

  18. Interspecies quantitative structure-toxicity-toxicity (QSTTR) relationship modeling of ionic liquids. Toxicity of ionic liquids to V. fischeri, D. magna and S. vacuolatus.

    PubMed

    Das, Rudra Narayan; Roy, Kunal; Popelier, Paul L A

    2015-12-01

    Considering the increasing uses of ionic liquids (ILs) in various industrial processes and chemical engineering operations, a complete assessment of their hazardous profile is essential. In the absence of adequate experimental data, in silico modeling might be helpful in filling data gaps for the toxicity of ILs towards various ecological indicator organisms. Using the rationale of taxonomic relatedness, the development of predictive quantitative structure-toxicity-toxicity relationship (QSTTR) models allows predicting the toxicity of ILs to a particular species using available experimental toxicity data towards a different species. Such studies may employ, along with the available experimental toxicity data to a species, molecular structure features and physicochemical properties of chemicals as independent variables for prediction of the toxicity profile against another closely related species. A few such interspecies toxicity correlation models have been reported in the literature for diverse chemicals in general, but this approach has been rarely applied to the class of ionic liquids. The present study involves the use of IL toxicity data towards the bacteria Vibrio fischeri along with molecular structure derived information or computational descriptors like extended topochemical atom (ETA) indices, quantum topological molecular similarity (QTMS) descriptors and computed lipophilicity measure (logk0) for the interspecies exploration of the toxicity data towards green algae S. vacuolatus and crustacea Daphnia magna, separately. This modeling study has been performed in accordance with the OECD guidelines. Finally, predictions for a true external set have been performed to fill the data gap of toxicity towards daphnids and algae using the Vibrio toxicity data and molecular structure attributes. PMID:26414597

  19. Decision support tools for proton therapy ePR: intelligent treatment planning navigator and radiation toxicity tool for evaluating of prostate cancer treatment

    NASA Astrophysics Data System (ADS)

    Le, Anh H.; Deshpande, Ruchi; Liu, Brent J.

    2010-03-01

    The electronic patient record (ePR) has been developed for prostate cancer patients treated with proton therapy. The ePR has functionality to accept digital input from patient data, perform outcome analysis and patient and physician profiling, provide clinical decision support and suggest courses of treatment, and distribute information across different platforms and health information systems. In previous years, we have presented the infrastructure of a medical imaging informatics based ePR for PT with functionality to accept digital patient information and distribute this information across geographical location using Internet protocol. In this paper, we present the ePR decision support tools which utilize the imaging processing tools and data collected in the ePR. The two decision support tools including the treatment plan navigator and radiation toxicity tool are presented to evaluate prostate cancer treatment to improve proton therapy operation and improve treatment outcomes analysis.

  20. Understanding Genetic Toxicity Through Data Mining: The Process of Building Knowledge by Integrating Multiple Genetic Toxicity Databases

    EPA Science Inventory

    This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in...

  1. Proposals accepted by the CEC

    SciTech Connect

    Not Available

    1987-06-01

    Descriptions are given of 12 geothermal projects approved by the California Energy Commission (CEC) for inclusion on the 1988-89 state budget. Projects include an aquaculture facility for mosquistofish to be used instead of toxic chemicals to control mosquitoes, an air monitoring program at The Geysers, a water quality baseline study for the Pieta Creek Basin within The Geysers KGRA, expansion of an existing geothermal district heating system, resource assessment and exploratory drilling on the Santa Ysabel Indian Reservation, and modifications and retrofit of space and water heating systems at two hospitals.

  2. Early and late toxicity of radiotherapy for rectal cancer.

    PubMed

    Joye, Ines; Haustermans, Karin

    2014-01-01

    With the implementation of total mesorectal excision surgery and neoadjuvant (chemo) radiotherapy, the outcome of rectal cancer patients has improved and a substantial proportion of them have become long-term survivors. These advances come at the expense of radiation- and chemotherapy-related toxicity which remains an underestimated problem. Radiation-induced early toxicity in rectal cancer treatment mainly includes diarrhea, cystitis, and perineal dermatitis, while bowel dysfunction, fecal incontinence, bleeding, and perforation, genitourinary dysfunction, and pelvic fractures constitute the majority of late toxicity. It is now generally accepted that short-course radiotherapy (SCRT) and immediate surgery is associated with less early toxicity compared to conventionally fractionated chemoradiotherapy with delayed surgery. There are no significant differences in late toxicity between both treatment regimens. While there is hardly an increase in early toxicity after preoperative SCRT with immediate surgery, late toxicity is substantial compared to surgery alone. Early toxicity is more frequent when a longer interval between SCRT and surgery is used and is comparable to the toxicity observed with conventionally fractionated radiotherapy except that it occurs after the end of the radiotherapy. So far, randomized phase III trials failed to demonstrate a substantial gain in tumoural response when oxaliplatin or molecular agents are added to the multimodality treatment. Moreover, the addition of these drugs increases toxicity and remains therefore experimental. PMID:25103006

  3. Health and environmental effects profile for formaldehyde

    SciTech Connect

    Not Available

    1985-10-01

    The Health and Environmental Effects Profile for formaldehyde was prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained from Agency program office files were evaluated as they pertained to potential human health, aquatic life, and environmental effects of hazardous-waste constituents. Quantitative estimates are presented, provided sufficient data are available. Existing data are insufficient to determine an Acceptable Daily Intake (ADI) or a carcinogenic potency factor for formaldehyde. The Reportable Quantity (RQ) value of 1, 10, 100, 1000, or 5000 pounds is used to determine the quantity of a hazardous substance for which notification is required in the event of a release as specified by CERCLA based on chronic toxicity. The RQ value for formaldehyde is 10.

  4. Screening of toxic potential of graphene family nanomaterials using in vitro and alternative in vivo toxicity testing systems

    PubMed Central

    Chatterjee, Nivedita; Yang, Ji Su; Park, Kwangsik; Oh, Seung Min; Park, Jeonggue; Choi, Jinhee

    2015-01-01

    Objectives The widely promising applications of graphene nanomaterials raise considerable concerns regarding their environmental and human health risk assessment. The aim of the current study was to evaluate the toxicity profiling of graphene family nananomaterials (GFNs) in alternative in vitro and in vivo toxicity testing models. Methods The GFNs used in this study are graphene nanoplatelets ([GNPs]–pristine, carboxylate [COOH] and amide [NH2]) and graphene oxides (single layer [SLGO] and few layers [FLGO]). The human bronchial epithelial cells (Beas2B cells) as in vitro system and the nematode Caenorhabditis elegans as in vivo system were used to profile the toxicity response of GFNs. Cytotoxicity assays, colony formation assay for cellular toxicity and reproduction potentiality in C. elegans were used as end points to evaluate the GFNs’ toxicity. Results In general, GNPs exhibited higher toxicity than GOs in Beas2B cells, and among the GNPs the order of toxicity was pristine>NH2>COOH. Although the order of toxicity of the GNPs was maintained in C. elegans reproductive toxicity, but GOs were found to be more toxic in the worms than GNPs. In both systems, SLGO exhibited profoundly greater dose dependency than FLGO. The possible reason of their differential toxicity lay in their distinctive physicochemical characteristics and agglomeration behavior in the exposure media. Conclusions The present study revealed that the toxicity of GFNs is dependent on the graphene nanomaterial’s physical forms, surface functionalizations, number of layers, dose, time of exposure and obviously, on the alternative model systems used for toxicity assessment. PMID:26602558

  5. Toxicity and outcomes of thoracic re-irradiation using stereotactic body radiation therapy (SBRT)

    PubMed Central

    2013-01-01

    Background Patients treated for a thoracic malignancy carry a significant risk of developing other lung lesions. Locoregional control of intrathoracic recurrences is challenging due to the impact of prior therapies on normal tissues. We examined the safety and efficacy of thoracic re-irradiation using high-precision image-guided stereotactic body radiation therapy (SBRT). Methods Records of 39 patients with prior intra-thoracic conventionally fractionated radiation therapy (RT) who underwent SBRT for a subsequent primary, recurrent or metastatic lung tumor from 11/2004 to 7/2011 were retrospectively reviewed. Results Median dose of prior RT was 61 Gy (range 30–80 Gy). Median biologically effective prescription dose (α/β = 10) (BED10) of SBRT was 70.4 Gy (range 42.6-180 Gy). With a median followup of 12.6 months among survivors, 1- and 2-year actuarial local progression-free survival (LPFS) were 77% and 64%, respectively. Median recurrence-free (RFS) and overall survival (OS) were 13.8 and 22.0 months, respectively. Patients without overlap of high-dose regions of the primary and re-irradiation plans were more likely to receive a BED10 ≥100 Gy, which was associated with higher LPFS (hazard ratio, [HR] = 0.18, p = 0.04), RFS ([HR] = 0.31, p = 0.038) and OS ([HR] = 0.25, p = 0.014). Grade 2 and 3 pulmonary toxicity was observed in 18% and 5% of patients, respectively. Other grade 2–4 toxicities included chest wall pain in 18%, fatigue in 15% and skin toxicity in 5%. No grade 5 events occurred. Conclusions SBRT can be safely and successfully administered to patients with prior thoracic RT. Dose reduction for cases with direct overlap of successive radiation fields results in acceptable re-treatment toxicity profile. PMID:23617949

  6. THE RARITY OF DNA PROFILES1

    PubMed Central

    Weir, Bruce S.

    2008-01-01

    It is now widely accepted that forensic DNA profiles are rare, so it was a surprise to some people that different people represented in offender databases are being found to have the same profile. In the first place this is just an illustration of the birthday problem, but a deeper analysis must take into account dependencies among profiles caused by family or population membership. PMID:19030117

  7. Smoke toxicity methodology

    NASA Technical Reports Server (NTRS)

    Dilley, J. V.; Martin, S. B.; Mckee, R.; Pryor, G.

    1978-01-01

    The toxicity of pyrolysis products for aircraft interior materials must be within some reasonable limit. The toxicity of pyrolysis products from five candidate aircraft materials is evaluated. The most important part of this study was to demonstrate that pyrolysis of materials could be controlled and biological endpoints are reproducible.

  8. Reproductive toxicity of brazilein in ICR mice.

    PubMed

    Yuan, Zhi-Yi; Lei, Fan; Chai, Yu-Shuang; Wu, Hao; Zhao, Shuang; Wang, Yu-Gang; Feng, Tian-Shi; Li, Hui-Ying; Li, Hui-Yu; Zhan, Hong-Lei; Xing, Dong-Ming; DU, Li-Jun

    2016-06-01

    Brazilein is an active small molecular compound extracted from Caesalpinia sappan L. with favorable pharmacological properties on immune system, cardiovascular system, and nervous system. C. sappan has been used as a traditional medicine in China for hundreds of years for various diseases. However, the general reproductive toxicity of brazilein is still unknown. The purpose of the present study was to thoroughly evaluate the general reproductive toxicity of brazilein in ICR mice to support the future drug development and modernization of this potent traditional Chinese medicine. The results showed that, although no apparent toxicity on the reproducibility of the male was observed, brazilein might cause considerable risks to the fetuses and females as indicated by the ratios of dead fetuses and reabsorptions. In conclusion, our results from the present study provided some useful insights about the safety profile of brazilein, suggesting that brazilein should be used with caution in pregnant women. PMID:27473962

  9. 48 CFR 811.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Market acceptance. 811.103 Section 811.103 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS COMPETITION AND... acceptance....

  10. 48 CFR 811.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Market acceptance. 811.103 Section 811.103 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS COMPETITION AND... acceptance....

  11. Computer acceptance of older adults.

    PubMed

    Nägle, Sibylle; Schmidt, Ludger

    2012-01-01

    Even though computers play a massive role in everyday life of modern societies, older adults, and especially older women, are less likely to use a computer, and they perform fewer activities on it than younger adults. To get a better understanding of the factors affecting older adults' intention towards and usage of computers, the Unified Theory of Acceptance and Usage of Technology (UTAUT) was applied as part of a more extensive study with 52 users and non-users of computers, ranging in age from 50 to 90 years. The model covers various aspects of computer usage in old age via four key constructs, namely performance expectancy, effort expectancy, social influences, and facilitating conditions, as well as the variables gender, age, experience, and voluntariness it. Interestingly, next to performance expectancy, facilitating conditions showed the strongest correlation with use as well as with intention. Effort expectancy showed no significant correlation with the intention of older adults to use a computer. PMID:22317258

  12. Mechanisms of phosphine toxicity.

    PubMed

    Nath, Nisa S; Bhattacharya, Ishita; Tuck, Andrew G; Schlipalius, David I; Ebert, Paul R

    2011-01-01

    Fumigation with phosphine gas is by far the most widely used treatment for the protection of stored grain against insect pests. The development of high-level resistance in insects now threatens its continued use. As there is no suitable chemical to replace phosphine, it is essential to understand the mechanisms of phosphine toxicity to increase the effectiveness of resistance management. Because phosphine is such a simple molecule (PH(3)), the chemistry of phosphorus is central to its toxicity. The elements above and below phosphorus in the periodic table are nitrogen (N) and arsenic (As), which also produce toxic hydrides, namely, NH(3) and AsH(3). The three hydrides cause related symptoms and similar changes to cellular and organismal physiology, including disruption of the sympathetic nervous system, suppressed energy metabolism and toxic changes to the redox state of the cell. We propose that these three effects are interdependent contributors to phosphine toxicity. PMID:21776261

  13. Management of digoxin toxicity

    PubMed Central

    Pincus, Matthew

    2016-01-01

    Summary Digoxin toxicity can emerge during long-term therapy as well as after an overdose. It can occur even when the serum digoxin concentration is within the therapeutic range. Toxicity causes anorexia, nausea, vomiting and neurological symptoms. It can also trigger fatal arrhythmias. There is a range of indications for using digoxin-specific antibody fragments. The amount ingested and serum digoxin concentration help to determine the dose required, but are not essential. Digoxin-specific antibody fragments are safe and effective in severe toxicity. Monitoring should continue after treatment because of the small risk of rebound toxicity. Restarting therapy should take into account the indication for digoxin and any reasons why the concentration became toxic. PMID:27041802

  14. Evaluation of multiple mechanism-based toxicity endpoints in primary cultured human hepatocytes for the identification of drugs with clinical hepatotoxicity: Results from 152 marketed drugs with known liver injury profiles.

    PubMed

    Zhang, Jie; Doshi, Utkarsh; Suzuki, Ayako; Chang, Ching-Wei; Borlak, Jürgen; Li, Albert P; Tong, Weida

    2016-08-01

    We report here the results of a collaborative research program to develop a robust and reliable in vitro system to allow an accurate definition of the drug-induced liver injury (DILI) potential of new drug entities during drug development. The in vitro hepatotoxic potential of 152 drugs with known DILI profiles were evaluated in primary cultured human hepatocytes with four mechanistically-relevant endpoints: cellular ATP depletion, reactive oxygen species (ROS), glutathione (GSH) depletion, and caspase activation for apoptosis. The drugs, 80 in the testing set and 72 in the validation set, were classified based on serious clinical/regulatory outcomes as defined by reported acute liver failure, black-box warning, and/or withdrawal. The drugs were further sub-categorized for dominant types of liver injury. Logistic regression models were performed to calculate the area under the receiver operating characteristics curve (AUROC) and to evaluate the prediction potential of the selected endpoints for serious clinical/regulatory outcomes. The ROS/ATP ratio was found to yield an excellent AUROC in both the testing (0.8989, P < 0.0001) and validation set (0.8545, P < 0.0001), and was found to distinguish drugs associated with severe from non-severe DILI cases (p < 0.0001). The results suggest that evaluation of drugs in primary human hepatocytes using the ROS/ATP ratio endpoint may aid the definition of their potential to cause severe DILI. PMID:26581450

  15. Ammonia and sediment toxicity

    SciTech Connect

    Ogle, R.S.; Hansen, S.R.

    1994-12-31

    Ammonia toxicity to aquatic organisms has received considerable study, with most of these studies focusing on water column organisms. However, with the development and implementation of sediment (and pore water) toxicity tests, the toxicity of ammonia to benthic infauna and other sediment toxicity test organisms has become important, especially since sediment/porewater ammonia occurs at higher concentrations than in the water column. Unfortunately, there has been very little of this type information, especially for marine/estuarine organisms. This laboratory determined the toxicity of ammonia to three key marine/estuarine test organisms: the amphipod Eohaustorius estuarius, the bivalve Mytilus edulis, and the echinoderm Strongylocentrotus purpuratus. Because sediment/porewater pH can differ substantially from typical seawater pH, the toxicity evaluations covered a range of pH levels (6, 7, 8, and 9). Eohaustorius results indicate that while Total Ammonia increased in toxicity (measured as EC50) as pH increased (from 460 mg/L at pH 6, to 13 mg/L at pH 9), unionized ammonia toxicity decreased from 0.13 mg/L at pH 6 to 2.8 mg/L at pH 9. The amphipod was much less sensitive to ammonia than were the bivalve and echinoderm, with an unionized ammonia EC50 at pH 8 of 2.14 mg/L relative to 0.43 mg/L for the mussel and 0.13 mg/L for the purple urchin. These results are discussed with respect to design and interpretation of sediment toxicity test results, including an interpretation approach based on partitioning of Toxic Units (TU).

  16. Polymyxin E sulfate-loaded liposome for intravenous use: preparation, lyophilization, and toxicity assessment in vivo.

    PubMed

    Wang, Dongkai; Kong, Liwen; Wang, Jing; He, Xiaoling; Li, Xiang; Xiao, Yuting

    2009-01-01

    Polymyxin E sulfate, a hydrophilic drug with high tissue toxicity, was formulated into a stable liposome to reduce its in vivo toxicity. The liposome was prepared using both a reverse phase evaporation and freezing-thawing method. The encapsulation efficiency was determined by high-performance liquid chromatography. The influence of the freezing-thawing process on the liposome's stability was evaluated using a centrifugation test. The dialysis method was employed to investigate the in vitro release profile of the drug-loaded liposome. The toxicity of the polymyxin E sulfate-loaded liposome was compared with the polymyxin E sulfate solution in Kunming mice by intravenous administration. A freeze-drying (lyophilization) technique was utilized to prepare the proliposome. A cryoprotectant formulation was optimized by the evaluation of the particle diameter and encapsulation efficiency of the redispersed proliposomes, while the influence of the concentration and method of the addition of the cryoprotectant on the protective effect was investigated as well. It was found that the stability and encapsulation efficiency of the liposome could be improved by the freezing-thawing process. The delayed drug release profile of the drug-loaded liposome was observed in vitro, and a comparison with the polymyxin E sulfate solution revealed that the in vivo toxicity of the polymyxin E sulfate-loaded liposome was significantly reduced. Sucrose and mannitol at a weight ratio of 1:0.8:0.6 (phospholipids:mannitol:sucrose) added inside displayed the greatest protective effect on the polymyxin E sulfate liposome during freeze-drying. The rehydrated proliposomes with optimized cryoprotectants produced an acceptable particle diameter (204.1 nm) and a satisfactory encapsulation efficiency percentage (51.48%), thus demonstrating a practical method for preparation of polymyxin E sulfate-loaded proliposome. A combination of the reverse phase evaporation and freezing-thawing methods was found to

  17. 7 CFR 966.29 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 966.29 Section 966.29 Agriculture... Regulating Handling Committee § 966.29 Acceptance. Any person selected as a committee member or alternate shall qualify by filing a written acceptance with the Secretary within ten days after being notified...

  18. 7 CFR 924.25 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 924.25 Section 924.25 Agriculture....25 Acceptance. Any person selected by the Secretary as a member or as an alternate member of the committee shall qualify by filing a written acceptance with the Secretary promptly after being notified...

  19. 7 CFR 924.25 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 924.25 Section 924.25 Agriculture....25 Acceptance. Any person selected by the Secretary as a member or as an alternate member of the committee shall qualify by filing a written acceptance with the Secretary promptly after being notified...

  20. 7 CFR 923.25 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 923.25 Section 923.25 Agriculture... COUNTIES IN WASHINGTON Order Regulating Handling Administrative Body § 923.25 Acceptance. Any person prior... written acceptance of willingness to serve on the committee....

  1. 7 CFR 993.31 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 993.31 Section 993.31 Agriculture... Order Regulating Handling Prune Marketing Committee § 993.31 Acceptance. Each person selected as a... with the Secretary a written acceptance within 15 days after receiving notice of his selection....

  2. 7 CFR 1215.23 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Acceptance. 1215.23 Section 1215.23 Agriculture... Acceptance. Each individual nominated for membership of the Board shall qualify by filing a written acceptance with the Secretary at the time of nomination....

  3. 7 CFR 906.25 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 906.25 Section 906.25 Agriculture... RIO GRANDE VALLEY IN TEXAS Order Regulating Handling Committee § 906.25 Acceptance. Any person selected as a committee member or alternate shall qualify by filing a written acceptance with the...

  4. 7 CFR 946.26 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 946.26 Section 946.26 Agriculture... Order Regulating Handling Administrative Committee § 946.26 Acceptance. Any person selected by the Secretary as a committee member or as an alternate shall qualify by filing a written acceptance with...

  5. 7 CFR 959.29 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 959.29 Section 959.29 Agriculture... Regulating Handling Committee § 959.29 Acceptance. Any person selected as a committee member or alternate shall qualify by filing a written acceptance within ten days after being notified of such selection....

  6. 12 CFR 250.164 - Bankers' acceptances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Bankers' acceptances. 250.164 Section 250.164... MISCELLANEOUS INTERPRETATIONS Interpretations § 250.164 Bankers' acceptances. (a) Section 207 of the Bank Export... bankers' acceptances (“BAs”) that may be created by an individual member bank from 50 per cent (or 100...

  7. 24 CFR 3282.355 - Submission acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 false Submission acceptance. 3282.355... § 3282.355 Submission acceptance. (a) A party whose submission is determined by the Department to be adequate shall be granted provisional acceptance until December 15, 1976, or for a six month period...

  8. 7 CFR 906.25 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 906.25 Section 906.25 Agriculture... RIO GRANDE VALLEY IN TEXAS Order Regulating Handling Committee § 906.25 Acceptance. Any person selected as a committee member or alternate shall qualify by filing a written acceptance with the...

  9. 24 CFR 3282.355 - Submission acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Submission acceptance. 3282.355... § 3282.355 Submission acceptance. (a) A party whose submission is determined by the Department to be adequate shall be granted provisional acceptance until December 15, 1976, or for a six month period...

  10. 48 CFR 11.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Market acceptance. 11.103... DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 11.103 Market acceptance. (a) Section... either— (i) Achieved commercial market acceptance; or (ii) Been satisfactorily supplied to an...

  11. 7 CFR 1250.330 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Acceptance. 1250.330 Section 1250.330 Agriculture... Research and Promotion Order Egg Board § 1250.330 Acceptance. Any person appointed by the Secretary as a member, or as an alternate member, of the Board shall qualify by filing a written acceptance with...

  12. 7 CFR 923.25 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 923.25 Section 923.25 Agriculture... COUNTIES IN WASHINGTON Order Regulating Handling Administrative Body § 923.25 Acceptance. Any person prior... written acceptance of willingness to serve on the committee....

  13. 7 CFR 1205.326 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Acceptance. 1205.326 Section 1205.326 Agriculture... Research and Promotion Order Cotton Board § 1205.326 Acceptance. Any person selected by the Secretary as a member or as an alternate member of the Board shall qualify by filing a written acceptance with...

  14. 7 CFR 953.21 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 953.21 Section 953.21 Agriculture... STATES Order Regulating Handling Administrative Committee § 953.21 Acceptance. Any person selected by the... acceptance with the Secretary within the time specified by the Secretary....

  15. 12 CFR 250.164 - Bankers' acceptances.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Bankers' acceptances. 250.164 Section 250.164... MISCELLANEOUS INTERPRETATIONS Interpretations § 250.164 Bankers' acceptances. (a) Section 207 of the Bank Export... bankers' acceptances (“BAs”) that may be created by an individual member bank from 50 per cent (or 100...

  16. 7 CFR 966.29 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 966.29 Section 966.29 Agriculture... Regulating Handling Committee § 966.29 Acceptance. Any person selected as a committee member or alternate shall qualify by filing a written acceptance with the Secretary within ten days after being notified...

  17. 48 CFR 2911.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Market acceptance. 2911... DESCRIBING AGENCY NEEDS Selecting And Developing Requirements Documents 2911.103 Market acceptance. The... offered have either achieved commercial market acceptance or been satisfactorily supplied to an...

  18. 7 CFR 1215.23 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Acceptance. 1215.23 Section 1215.23 Agriculture... Acceptance. Each individual nominated for membership of the Board shall qualify by filing a written acceptance with the Secretary at the time of nomination....

  19. 7 CFR 946.26 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 946.26 Section 946.26 Agriculture... Order Regulating Handling Administrative Committee § 946.26 Acceptance. Any person selected by the Secretary as a committee member or as an alternate shall qualify by filing a written acceptance with...

  20. 7 CFR 1205.326 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Acceptance. 1205.326 Section 1205.326 Agriculture... Research and Promotion Order Cotton Board § 1205.326 Acceptance. Any person selected by the Secretary as a member or as an alternate member of the Board shall qualify by filing a written acceptance with...

  1. 7 CFR 953.21 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 953.21 Section 953.21 Agriculture... STATES Order Regulating Handling Administrative Committee § 953.21 Acceptance. Any person selected by the... acceptance with the Secretary within the time specified by the Secretary....

  2. 7 CFR 1250.330 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Acceptance. 1250.330 Section 1250.330 Agriculture... Research and Promotion Order Egg Board § 1250.330 Acceptance. Any person appointed by the Secretary as a member, or as an alternate member, of the Board shall qualify by filing a written acceptance with...

  3. 48 CFR 2911.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Market acceptance. 2911... DESCRIBING AGENCY NEEDS Selecting And Developing Requirements Documents 2911.103 Market acceptance. The... offered have either achieved commercial market acceptance or been satisfactorily supplied to an...

  4. 48 CFR 11.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Market acceptance. 11.103... DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 11.103 Market acceptance. (a) Section... either— (i) Achieved commercial market acceptance; or (ii) Been satisfactorily supplied to an...

  5. 7 CFR 1210.323 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Acceptance. 1210.323 Section 1210.323 Agriculture... PLAN Watermelon Research and Promotion Plan National Watermelon Promotion Board § 1210.323 Acceptance. Each person nominated for membership on the Board shall qualify by filing a written acceptance with...

  6. 7 CFR 959.29 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 959.29 Section 959.29 Agriculture... Regulating Handling Committee § 959.29 Acceptance. Any person selected as a committee member or alternate shall qualify by filing a written acceptance within ten days after being notified of such selection....

  7. 7 CFR 993.31 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 993.31 Section 993.31 Agriculture... Order Regulating Handling Prune Marketing Committee § 993.31 Acceptance. Each person selected as a... with the Secretary a written acceptance within 15 days after receiving notice of his selection....

  8. 7 CFR 915.25 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 915.25 Section 915.25 Agriculture... Regulating Handling Administrative Body § 915.25 Acceptance. Any person selected by the Secretary as a member or as an alternate member of the committee shall qualify by filing a written acceptance with...

  9. 7 CFR 1210.323 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Acceptance. 1210.323 Section 1210.323 Agriculture... PLAN Watermelon Research and Promotion Plan National Watermelon Promotion Board § 1210.323 Acceptance. Each person nominated for membership on the Board shall qualify by filing a written acceptance with...

  10. 46 CFR 28.73 - Accepted organizations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Accepted organizations. 28.73 Section 28.73 Shipping... INDUSTRY VESSELS General Provisions § 28.73 Accepted organizations. An organization desiring to be designated by the Commandant as an accepted organization must request such designation in writing. As...

  11. Older Adults' Acceptance of Information Technology

    ERIC Educational Resources Information Center

    Wang, Lin; Rau, Pei-Luen Patrick; Salvendy, Gavriel

    2011-01-01

    This study investigated variables contributing to older adults' information technology acceptance through a survey, which was used to find factors explaining and predicting older adults' information technology acceptance behaviors. Four factors, including needs satisfaction, perceived usability, support availability, and public acceptance, were…

  12. 48 CFR 11.103 - Market acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Market acceptance. 11.103... DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 11.103 Market acceptance. (a) Section... either— (i) Achieved commercial market acceptance; or (ii) Been satisfactorily supplied to an...

  13. 48 CFR 11.103 - Market acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Market acceptance. 11.103... DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 11.103 Market acceptance. (a) 41 U.S...) Achieved commercial market acceptance; or (ii) Been satisfactorily supplied to an agency under current...

  14. 48 CFR 2911.103 - Market acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Market acceptance. 2911... DESCRIBING AGENCY NEEDS Selecting And Developing Requirements Documents 2911.103 Market acceptance. The... offered have either achieved commercial market acceptance or been satisfactorily supplied to an...

  15. 48 CFR 11.103 - Market acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Market acceptance. 11.103... DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 11.103 Market acceptance. (a) Section... either— (i) Achieved commercial market acceptance; or (ii) Been satisfactorily supplied to an...

  16. 48 CFR 2911.103 - Market acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Market acceptance. 2911.103... DESCRIBING AGENCY NEEDS Selecting And Developing Requirements Documents 2911.103 Market acceptance. The... offered have either achieved commercial market acceptance or been satisfactorily supplied to an...

  17. 48 CFR 2911.103 - Market acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Market acceptance. 2911... DESCRIBING AGENCY NEEDS Selecting And Developing Requirements Documents 2911.103 Market acceptance. The... offered have either achieved commercial market acceptance or been satisfactorily supplied to an...

  18. The Relationship between Treatment Acceptability and Familism

    ERIC Educational Resources Information Center

    Pemberton, Joy R.; Borrego, Joaquin, Jr.

    2005-01-01

    Many studies have examined the acceptability of treatments for children with disruptive behaviors. However, few studies to date have tested the effects of home environment variables such as family support on treatment acceptability. In the current study, parents' level of familism was used to predict their willingness to accept several behavioral…

  19. 46 CFR 28.73 - Accepted organizations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Accepted organizations. 28.73 Section 28.73 Shipping... INDUSTRY VESSELS General Provisions § 28.73 Accepted organizations. An organization desiring to be designated by the Commandant as an accepted organization must request such designation in writing. As...

  20. COMPARISON OF EFFLUENT TOXICITY RESULTS USING CERIODAPHNIA DUBIA CULTURED ON SEVERAL DIETS

    EPA Science Inventory

    Several diets have been proposed for Ceriodaphnia dubia, but no single diet has been universally accepted as optimal for toxicity testing. lthough several diets for Ceriodaphnia dubia culturing and testing are commonly used, little or no data exist on whether toxicity varies with...

  1. DEVELOPMENT OF PROTOCOLS FOR CHRONIC TOXICITY TESTING OF PACIFIC MARINE SPECIES

    EPA Science Inventory

    Development of a year-round capability for conducting short-term toxicity tests for estimating chronic effect levels of toxic materials with a native Pacific coast fish and a native Pacific coast mysid shrimp was the goal of this project. n order to achieve acceptable sensitivity...

  2. Imprecision profiling.

    PubMed

    Sadler, William A

    2008-08-01

    * Imprecision profiles express precision characteristics of an assay over a range of concentration values. They can convert large quantities of potentially complex data into an easily interpreted graphical summary. * Imprecision profile estimation does not require precisely structured data. This implies that structured method evaluation data can be easily compared with, or merged with, less structured internal quality control (QC) data (or with data from any other source). * Although originally conceived for immunoassays, imprecision profiles could, in principle, be used as a summary method with any measurement system where precision varies with level of measurand. PMID:18852854

  3. Differences in gene expression profiles in the liver between carcinogenic and non-carcinogenic isomers of compounds given to rats in a 28-day repeat-dose toxicity study.

    PubMed

    Nakayama, Koji; Kawano, Yukiko; Kawakami, Yuuki; Moriwaki, Norichika; Sekijima, Masaru; Otsuka, Masanori; Yakabe, Yoshikuni; Miyaura, Hideki; Saito, Koichi; Sumida, Kayo; Shirai, Tomoyuki

    2006-12-15

    Some compounds have structural isomers of which one is apparently carcinogenic, and the other not. Because of the similarity of their chemical structures, comparisons of their effects can allow gene expression elicited in response to the basic skeletons of the isomers to be disregarded. We compared the gene expression profiles of male Fischer 344 rats administered by daily oral gavage up to 28 days using an in-house oligo microarray. 2-Acetylaminofluorene (2-AAF), 2,4-diaminotoluene (2,4-DAT), 2-nitropropane (2-NP), and 2-nitro-p-phenylenediamine (2-NpP) are hepatocarcinogenic. However, their isomers, 4-acetylaminofluorene (4-AAF), 2,6-diaminotoluene (2,6-DAT), 1-nitropropane (1-NP), and 4-nitro-o-phenylenediamine (4-NoP), are non-hepatocarcinogenic. Because of the limited carcinogenicity of 2-NpP, we attempted to perform two-parametric comparison analyses with (1) a set of 4 isomers: 2-AAF, 2,4-DAT, 2-NP, and 2-NpP as "carcinogenic", and 4-AAF, 2,6-DAT, 1-NP, and 4-NoP as "non-carcinogenic"; and (2) a set of 3 isomers: 2-AAF, 2,4-DAT, and 2-NP, as "carcinogenic", and 4-AAF, 2,6-DAT, and 1-NP as "non-carcinogenic". After ratio filtering and Welch's approximate t-test analysis, 54 and 28 genes were selected from comparisons between the sets of 3 and 4 isomers, respectively, for day 28 data. Using hierarchical clustering analysis with the 54 or 28 genes, 2-AAF, 2,4-DAT, and 2-NP clustered into a "carcinogenic" branch. 2-NpP was in the same cluster as 4-NoP and 4-AAF. This clustering corresponded to the previous finding that 2-NpP is not carcinogenic in male Fischer 344 rats, which indicates that comparing the differences in gene expression elicited by different isomers is an effective method of developing a prediction system for carcinogenicity. PMID:17070881

  4. Assessing Nanoparticle Toxicity

    NASA Astrophysics Data System (ADS)

    Love, Sara A.; Maurer-Jones, Melissa A.; Thompson, John W.; Lin, Yu-Shen; Haynes, Christy L.

    2012-07-01

    Nanoparticle toxicology, an emergent field, works toward establishing the hazard of nanoparticles, and therefore their potential risk, in light of the increased use and likelihood of exposure. Analytical chemists can provide an essential tool kit for the advancement of this field by exploiting expertise in sample complexity and preparation as well as method and technology development. Herein, we discuss experimental considerations for performing in vitro nanoparticle toxicity studies, with a focus on nanoparticle characterization, relevant model cell systems, and toxicity assay choices. Additionally, we present three case studies (of silver, titanium dioxide, and carbon nanotube toxicity) to highlight the important toxicological considerations of these commonly used nanoparticles.

  5. Acceptability of GM foods among Pakistani consumers.

    PubMed

    Ali, Akhter; Rahut, Dil Bahadur; Imtiaz, Muhammad

    2016-04-01

    In Pakistan majority of the consumers do not have information about genetically modified (GM) foods. In developing countries particularly in Pakistan few studies have focused on consumers' acceptability about GM foods. Using comprehensive primary dataset collected from 320 consumers in 2013 from Pakistan, this study analyzes the determinants of consumers' acceptability of GM foods. The data was analyzed by employing the bivariate probit model and censored least absolute deviation (CLAD) models. The empirical results indicated that urban consumers are more aware of GM foods compared to rural consumers. The acceptance of GM foods was more among females' consumers as compared to male consumers. In addition, the older consumers were more willing to accept GM food compared to young consumers. The acceptability of GM foods was also higher among wealthier households. Low price is the key factor leading to the acceptability of GM foods. The acceptability of the GM foods also reduces the risks among Pakistani consumers. PMID:27494790

  6. A nontoxic case of vitamin D toxicity.

    PubMed

    Chakraborty, Sutirtha; Sarkar, Ajoy Krishna; Bhattacharya, Chandramouli; Krishnan, Prasad; Chakraborty, Subhosmito

    2015-01-01

    Vitamin D toxicity also known as hypervitaminosis D was previously believed to be rare. But with an increase in vitamin D supplementation several cases have been reported in literature. Fat soluble vitamins like Vitamin D, due to their ability to accumulate in the body, have a higher potential for toxicity than water soluble vitamins. The main clinical consequence of vitamin D toxicity is hypercalcemia. In this report we describe an adult female patient who developed very high serum Vitamin D levels (746 ng/mL, RI: 20 to 50) as a result of medication error. Inspite of such high serum concentrations the patient was without any clinical symptoms and had normal serum calcium. We critically discuss the mechanism of toxicity and hypothesize the possible molecular/metabolic factors which might have been responsible for this nontoxic presentation. This case study highlights the fact that physicians need to consider the risk of medication errors while prescribing Vitamin D therapy. Clinical trials to study Vitamin D toxicity in humans is not possible ethically. Thus the evidence base regarding the safety profile of Vitamin D supplementation in humans has been build through case reports. This review of the paradoxical clinico-laboratory manifestation of hypervitaminosis D could possibly contribute to existing literature. PMID:25918194

  7. Leadership Profiles.

    ERIC Educational Resources Information Center

    Teach, Beverly; And Others

    1994-01-01

    Presents profiles of two leaders in the field of educational media and technology: Carolyn Guss and Mendel Sherman, both retired professors from Indiana University's program in Information Systems Technology. (KRN)

  8. Pioneer Profile.

    ERIC Educational Resources Information Center

    Butcher, Channa Beth

    1987-01-01

    Profiles Herbert A. Sweet, founder and director of Acorn Farms Day Camp (Indiana) for 44 years. Includes reminiscences about the camp's program, staffing, food, World War II, affiliation with the American Camping Association, and camps/directors of today. (NEC)

  9. Acceptance in Romantic Relationships: The Frequency and Acceptability of Partner Behavior Inventory

    ERIC Educational Resources Information Center

    Doss, Brian D.; Christensen, Andrew

    2006-01-01

    Despite the recent emphasis on acceptance in romantic relationships, no validated measure of relationship acceptance presently exists. To fill this gap, the 20-item Frequency and Acceptability of Partner Behavior Inventory (FAPBI; A. Christensen & N. S. Jacobson, 1997) was created to assess separately the acceptability and frequency of both…

  10. BIOMARKERS OF REPRODUCTIVE TOXICITY

    EPA Science Inventory

    Identification and verification of anatomical, endocrine, cellular and molecular biomarkers is crucial for successful clinical diagnosis and treatment of toxicity and disease, as well as basic toxicological, epidemiological and other research. Various in situ biomarkers of repro...

  11. Toxic shock syndrome

    MedlinePlus

    ... by a toxin produced by some types of Staphylococcus bacteria. A similar problem, called toxic shock-like ... men. Risk factors include: Recent childbirth Infection with Staphylococcus aureus ( S. aureus ), commonly called a Staph infection Foreign ...

  12. Contact Lens Solution Toxicity

    MedlinePlus

    ... rash and rashes clinical tools newsletter | contact Share | Contact Lens Solution Toxicity Information for adults A A A This image shows a reaction to contact lens solution. The prominent blood vessels and redness ...

  13. Aspects of aluminum toxicity

    SciTech Connect

    Hewitt, C.D.; Savory, J.; Wills, M.R. )

    1990-06-01

    Aluminum is the most abundant metal in the earth's crust. The widespread occurrence of aluminum, both in the environment and in foodstuffs, makes it virtually impossible for man to avoid exposure to this metal ion. Attention was first drawn to the potential role of aluminum as a toxic metal over 50 years ago, but was dismissed as a toxic agent as recently as 15 years ago. The accumulation of aluminum, in some patients with chronic renal failure, is associated with the development of toxic phenomena; dialysis encephalopathy, osteomalacic dialysis osteodystrophy, and an anemia. Aluminum accumulation also occurs in patients who are not on dialysis, predominantly infants and children with immature or impaired renal function. Aluminum has also been implicated as a toxic agent in the etiology of Alzheimer's disease, Guamiam amyotrophic lateral sclerosis, and parkinsonism-dementia. 119 references.

  14. Toxic inhalational exposures.

    PubMed

    Chen, Tze-Ming Benson; Malli, Harjoth; Maslove, David M; Wang, Helena; Kuschner, Ware G

    2013-01-01

    Respirable toxicants are a spectrum of irritant and nonirritant gases, vapors, fumes, and airborne particles that can be entrained into the body through the respiratory tract, resulting in exposures that cause pulmonary injury and/or systemic disease. Sources of respirable toxicants include structural fires, industrial accidents, domestic mishaps, and intentional releases of injurious agents on the battleground (warfare) or in civilian settings (acts of terrorism). Acute toxic inhalational exposures may result in respiratory failure, multisystem organ dysfunction, and death. Management of victims includes assessment and protection of the airway, monitoring and treatment of systemic toxicity, and delivery of exposure-specific and nonspecific therapies that improve outcomes. Treatments may include antidotes, hyperbaric oxygen, and other nonspecific life-supporting interventions. PMID:22232204

  15. Cadmium Toxicity and Treatment

    PubMed Central

    Bernhoft, Robin A.

    2013-01-01

    Cadmium is a heavy metal of considerable toxicity with destructive impact on most organ systems. It is widely distributed in humans, the chief sources of contamination being cigarette smoke, welding, and contaminated food and beverages. Toxic impacts are discussed and appear to be proportional to body burden of cadmium. Detoxification of cadmium with EDTA and other chelators is possible and has been shown to be therapeutically beneficial in humans and animals when done using established protocols. PMID:23844395

  16. 2013 SYR Accepted Poster Abstracts.

    PubMed

    2013-01-01

    SYR 2013 Accepted Poster abstracts: 1. Benefits of Yoga as a Wellness Practice in a Veterans Affairs (VA) Health Care Setting: If You Build It, Will They Come? 2. Yoga-based Psychotherapy Group With Urban Youth Exposed to Trauma. 3. Embodied Health: The Effects of a Mind�Body Course for Medical Students. 4. Interoceptive Awareness and Vegetable Intake After a Yoga and Stress Management Intervention. 5. Yoga Reduces Performance Anxiety in Adolescent Musicians. 6. Designing and Implementing a Therapeutic Yoga Program for Older Women With Knee Osteoarthritis. 7. Yoga and Life Skills Eating Disorder Prevention Among 5th Grade Females: A Controlled Trial. 8. A Randomized, Controlled Trial Comparing the Impact of Yoga and Physical Education on the Emotional and Behavioral Functioning of Middle School Children. 9. Feasibility of a Multisite, Community based Randomized Study of Yoga and Wellness Education for Women With Breast Cancer Undergoing Chemotherapy. 10. A Delphi Study for the Development of Protocol Guidelines for Yoga Interventions in Mental Health. 11. Impact Investigation of Breathwalk Daily Practice: Canada�India Collaborative Study. 12. Yoga Improves Distress, Fatigue, and Insomnia in Older Veteran Cancer Survivors: Results of a Pilot Study. 13. Assessment of Kundalini Mantra and Meditation as an Adjunctive Treatment With Mental Health Consumers. 14. Kundalini Yoga Therapy Versus Cognitive Behavior Therapy for Generalized Anxiety Disorder and Co-Occurring Mood Disorder. 15. Baseline Differences in Women Versus Men Initiating Yoga Programs to Aid Smoking Cessation: Quitting in Balance Versus QuitStrong. 16. Pranayam Practice: Impact on Focus and Everyday Life of Work and Relationships. 17. Participation in a Tailored Yoga Program is Associated With Improved Physical Health in Persons With Arthritis. 18. Effects of Yoga on Blood Pressure: Systematic Review and Meta-analysis. 19. A Quasi-experimental Trial of a Yoga based Intervention to Reduce Stress and

  17. Hydroxychloroquine-related retinal toxicity.

    PubMed

    Ding, Hui Jen; Denniston, Alastair K; Rao, Vijay K; Gordon, Caroline

    2016-06-01

    HCQ is widely used for the treatment of rheumatic diseases, particularly lupus and RA. It is generally well tolerated, but retinopathy is a concern. Retinopathy is rare, but is sight threatening, generally irreversible and may progress even after cessation of therapy. Damage may be subclinical. Although a number of risk factors have been proposed (such as duration of therapy and cumulative dose), the many exceptions (e.g. retinopathy on low-dose HCQ, or no retinopathy after a very large cumulative dose of HCQ) highlight our limited understanding of the disease process. Novel technologies such as optical coherence tomography (OCT), fundus autofluorescence (FAF) and multifocal electroretinogram (mfERG) may provide the earliest structural and functional evidence of toxicity in these stages. Along with the well-established technique of central visual field testing (10-2 visual fields), these modalities are increasingly being used as part of screening programmes. The ideal single test with high sensitivity and high specificity for HCQ retinopathy has still not been achieved. Screening for HCQ retinopathy remains an area of considerable debate, including issues of when, who and how to screen. Commonly accepted risk factors include receiving >6.5 mg/kg/day or a cumulative dose of >1000 g of HCQ, being on treatment for >5 years, having renal or liver dysfunction, having pre-existing retinopathy and being elderly. HCQ continues to be a valuable drug in treating rheumatic disease, but clinicians need to be aware of the associated risks and to have arrangements in place that would enable early detection of toxicity. PMID:26428520

  18. Power equation for all-or-none effects of oxygen toxicity and cumulative oxygen toxicity.

    PubMed

    Arieli, R

    1994-01-01

    Quantification of the level of O2 toxicity may provide a means of setting limits on various hyperoxic exposures. A previously suggested expression for quantitative oxygen toxicity, DMG = a x t2 x PO2c (t-time, DMG-measured level of O2 toxicity), has been adapted for the all-or-none phenomenon: K = t2 x PO2c. A symptom may appear when K reaches a threshold value Kc. Non-linear regression was successfully applied to all-or-none symptoms from the literature: survival, convulsions, substernal distress, reduction in short circuit current and nerve conduction blockade. The generality of these expressions enabled calculation of cumulative oxygen toxicity and a search for the mechanism of oxygen toxicity. Cumulative oxygen toxicity is calculated in three-step calculation loops in three suggested exposure profiles. For a possible recovery period between exposures the expressions took the form: DMGt = DMGc x e-rt, and Kt = Kc x e-rt, where r is the recovery constant. A possibly bimodal distribution of c close to the values of 1 and 4 could be attributed to systemic effects. PMID:8736032

  19. Selective Toxicity at Low Doses: Experiments with Three Plant Species and Toxicants

    PubMed Central

    Sinkkonen, Aki; Myyrä, Mervi; Penttinen, Olli-Pekka; Rantalainen, Anna-Lea

    2010-01-01

    During the last decade, the paradigm that low toxicant doses often have stimulatory effects on plants has become widely accepted. At the same time, low toxicant doses of metal salts have been observed to inhibit the growth of the most vigorous seedlings of a population in vitro, although mean plant size has remained unaffected. We hypothesized that this kind of selective low-dose toxicity is not restricted to inorganic contaminants. We exposed annual plants (baby’s breath Gypsophila elegans, purslane Portulaca oleracea, and duckweed Lemna minor) to 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-γ-2-benzopyran (HHCB) and 4-tert-octylphenol and lead acetate. As compared to unexposed G. elegans roots, 4-tert-octylphenol did not affect the mean root size of all seedlings, but it reduced the average length of roots longer than the 98th percentile. A comparable response was found in case of G. elegans roots treated with lead acetate beyond the 90th percentile. The average size of roots beyond the 90th percentile was decreased also when L. minor was exposed to lead acetate though the means of all roots were constant. P. oleracea seemed to be insensitive to selective toxicity. We conclude that selective toxicity at low doses should be considered in parallel with hormesis. PMID:21431082

  20. Cryoprotectant toxicity neutralization.

    PubMed

    Fahy, Gregory M

    2010-07-01

    Cryoprotectant toxicity is a fundamental limiting factor for the successful cryopreservation of living systems by both freezing and vitrification, and the ability to negate it would be attractive. Past attempts to demonstrate "cryoprotectant toxicity neutralization" (CTN) have had many ups and downs. First convincingly introduced by Baxter and Lathe in 1971, the concept that certain amides can block toxic effects of dimethyl sulfoxide (Me(2)SO) was contradicted by direct experiments in 1990. But in 1995, the opposite mode of CTN, in which Me(2)SO blocked the damaging effects of formamide, was robustly demonstrated. Recent experiments have verified the original 1995 results and extended them to urea and acetamide, but no CTN was detected for N-methylamides (N-methylformamide, N,N-dimethylformamide, and N-methylacetamide). On the theory that the latter amides and acetamide might serve as low-toxicity structural analogs of formamide, urea, or Me(2)SO, competition experiments were carried out between them and formamide or urea, but CTN was not observed for these amide-amide systems. The idea that the N-methylamides might have non-specific rather than specific toxicity was supported by the fact that the concentrations of these amides that cause toxicity are similar to the concentrations that denature model proteins. Clear examples of neutralization of the toxicity of glycerol, propylene glycol, ethylene glycol, or Me(2)SO are presently lacking, but effects of the latter that depend on sulfhydryl oxidation have been reversed with reducing agents. In summary, CTN is a useful phenomenon with significant theoretical and practical implications. PMID:19501081

  1. 7 CFR 932.32 - Acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order Regulating Handling Olive Administrative Committee § 932.32 Acceptance. Any person selected by the...

  2. 7 CFR 932.32 - Acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order Regulating Handling Olive Administrative Committee § 932.32 Acceptance. Any person selected by the...

  3. 7 CFR 932.32 - Acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order Regulating Handling Olive Administrative Committee § 932.32 Acceptance. Any person selected by the...

  4. 7 CFR 1207.323 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan National Potato Promotion Board § 1207.323 Acceptance. Each...

  5. 7 CFR 1207.323 - Acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan National Potato Promotion Board § 1207.323 Acceptance. Each...

  6. 7 CFR 1207.323 - Acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan National Potato Promotion Board § 1207.323 Acceptance. Each...

  7. 7 CFR 1207.323 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan National Potato Promotion Board § 1207.323 Acceptance. Each...

  8. 7 CFR 1207.323 - Acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan National Potato Promotion Board § 1207.323 Acceptance. Each...

  9. PARTICLE SPECIATION AND EMISSION PROFILES OF SMALL 2-STROKE ENGINES

    EPA Science Inventory

    The Human Exposure and Atmospheric Sciences Division (HEASD) conducts studies designed to acquire information from emission sources for use in source apportionment studies. The objective of this work is to characterize a complete, speciated emission profile (PM and air toxics) ...

  10. In acceptance we trust? Conceptualising acceptance as a viable approach to NGO security management.

    PubMed

    Fast, Larissa A; Freeman, C Faith; O'Neill, Michael; Rowley, Elizabeth

    2013-04-01

    This paper documents current understanding of acceptance as a security management approach and explores issues and challenges non-governmental organisations (NGOs) confront when implementing an acceptance approach to security management. It argues that the failure of organisations to systematise and clearly articulate acceptance as a distinct security management approach and a lack of organisational policies and procedures concerning acceptance hinder its efficacy as a security management approach. The paper identifies key and cross-cutting components of acceptance that are critical to its effective implementation in order to advance a comprehensive and systematic concept of acceptance. The key components of acceptance illustrate how organisational and staff functions affect positively or negatively an organisation's acceptance, and include: an organisation's principles and mission, communications, negotiation, programming, relationships and networks, stakeholder and context analysis, staffing, and image. The paper contends that acceptance is linked not only to good programming, but also to overall organisational management and structures. PMID:23278470

  11. What Renders TAU Toxic

    PubMed Central

    Götz, Jürgen; Xia, Di; Leinenga, Gerhard; Chew, Yee Lian; Nicholas, Hannah R.

    2013-01-01

    TAU is a microtubule-associated protein that under pathological conditions such as Alzheimer’s disease (AD) forms insoluble, filamentous aggregates. When 20 years after TAU’s discovery the first TAU transgenic mouse models were established, one declared goal that was achieved was the modeling of authentic TAU aggregate formation in the form of neurofibrillary tangles. However, as we review here, it has become increasingly clear that TAU causes damage much before these filamentous aggregates develop. In fact, because TAU is a scaffolding protein, increased levels and an altered subcellular localization (due to an increased insolubility and impaired clearance) result in the interaction of TAU with cellular proteins with which it would otherwise either not interact or do so to a lesser degree, thereby impairing their physiological functions. We specifically discuss the non-axonal localization of TAU, the role phosphorylation has in TAU toxicity and how TAU impairs mitochondrial functions. A major emphasis is on what we have learned from the four available TAU knock-out models in mice, and the knock-out of the TAU/MAP2 homolog PTL-1 in worms. It has been proposed that in human pathological conditions such as AD, a rare toxic TAU species exists which needs to be specifically removed to abrogate TAU’s toxicity and restore neuronal functions. However, what is toxic in one context may not be in another, and simply reducing, but not fully abolishing TAU levels may be sufficient to abrogate TAU toxicity. PMID:23772223

  12. Lead toxicity: a review

    PubMed Central

    Ara, Anjum; Usmani, Jawed Ahmad

    2015-01-01

    Lead toxicity is an important environmental disease and its effects on the human body are devastating. There is almost no function in the human body which is not affected by lead toxicity. Though in countries like US and Canada the use of lead has been controlled up to a certain extent, it is still used vehemently in the developing countries. This is primarily because lead bears unique physical and chemical properties that make it suitable for a large number of applications for which humans have exploited its benefits from historical times and thus it has become a common environmental pollutant. Lead is highly persistent in the environment and because of its continuous use its levels rise in almost every country, posing serious threats. This article reviews the works listed in the literature with recent updates regarding the toxicity of lead. Focus is also on toxic effects of lead on the renal, reproductive and nervous system. Finally the techniques available for treating lead toxicity are presented with some recent updates. PMID:27486361

  13. Toxicity of lunar dust

    NASA Astrophysics Data System (ADS)

    Linnarsson, Dag; Carpenter, James; Fubini, Bice; Gerde, Per; Karlsson, Lars L.; Loftus, David J.; Prisk, G. Kim; Staufer, Urs; Tranfield, Erin M.; van Westrenen, Wim

    2012-12-01

    The formation, composition and physical properties of lunar dust are incompletely characterised with regard to human health. While the physical and chemical determinants of dust toxicity for materials such as asbestos, quartz, volcanic ashes and urban particulate matter have been the focus of substantial research efforts, lunar dust properties, and therefore lunar dust toxicity may differ substantially. In this contribution, past and ongoing work on dust toxicity is reviewed, and major knowledge gaps that prevent an accurate assessment of lunar dust toxicity are identified. Finally, a range of studies using ground-based, low-gravity, and in situ measurements is recommended to address the identified knowledge gaps. Because none of the curated lunar samples exist in a pristine state that preserves the surface reactive chemical aspects thought to be present on the lunar surface, studies using this material carry with them considerable uncertainty in terms of fidelity. As a consequence, in situ data on lunar dust properties will be required to provide ground truth for ground-based studies quantifying the toxicity of dust exposure and the associated health risks during future manned lunar missions.

  14. Profile video

    NASA Astrophysics Data System (ADS)

    Voglewede, Paul E.; Zampieron, Jeffrey

    2009-05-01

    For unattended persistent surveillance there is a need for a system which provides the following information: target classification, target quantity estimate, cargo presence and characterization, direction of travel, and action. Over highly bandwidth restricted links, such as Iridium, SATCOM or HF, the data rates of common techniques are too high, even after aggressive compression, to deliver the required intelligence in a timely, low power manner. We propose the following solution to this data rate problem: Profile Video. Profile video is a new technique which provides all of the required information in a very low data-rate package.

  15. Toxicity of adipic acid.

    PubMed

    Kennedy, Gerald L

    2002-05-01

    Adipic acid has very low acute toxicity in rats with an LD50 > 5000 mg/kg. Adipic acid produced mild to no skin irritation on intact guinea pig skin as a 50% concentration in propylene glycol; it was not a skin sensitizer. Adipic acid caused mild conjunctival irritation in washed rabbit eyes; in unwashed rabbit eyes, there was mild conjunctival irritation, minimal iritis, but no corneal effects. Adipic acid dust may irritate the mucous membranes of the lungs and nose. In a 2-year feeding study, rats fed adipic acid at concentrations up to 5% in the diet exhibited only weight loss. Adipic acid is not genetically active in a wide variety of assay systems. Adipic acid caused no developmental toxicity in mice, rats, rabbits, or hamsters when administered orally. Adipic acid is partially metabolized in humans; the balance is eliminated unchanged in the urine. Adipic acid is slightly to moderately toxic to fish, daphnia, and algae in acute tests. PMID:12024802

  16. Iron toxicity in yeast.

    PubMed

    Wiśnicka, R; Krzepiłko, A; Wawryn, J; Biliński, T

    1997-01-01

    It has been found that yeast cells are sensitive to iron overload only when grown on glucose as a carbon source. Effective concentration of ferrous iron is much higher than that found in natural environments. Effects of ferrous iron are strictly oxygen dependent, what suggest that the formation of hydroxyl radicals in the Fenton reaction is a cause of the toxicity. Respiratory deficiency and pretreatment of cells with antimycin A prevent toxic effects in the late exponential phase of growth, whereas uncouplers and 2mM magnesium salts completely protect even the most vulnerable exponential cells. Generally, toxic effects correlate with the ability of cells to take up this metal. The results presented suggest that during ferrous iron overload iron is transported through the unspecific divalent cation uptake system which is known in fungi. The data suggest that recently described high and low affinity systems of iron uptake in yeast are the only source of iron in natural environments. PMID:9516981

  17. PSP toxin levels and plankton community composition and abundance in size-fractionated vertical profiles during spring/summer blooms of the toxic dinoflagellate Alexandrium fundyense in the Gulf of Maine and on Georges Bank, 2007, 2008, and 2010: 1. Toxin levels

    PubMed Central

    Deeds, Jonathan R.; Petitpas, Christian M.; Shue, Vangie; White, Kevin D.; Keafer, Bruce A.; McGillicuddy, Dennis J.; Milligan, Peter J.; Anderson, Donald M.; Turner, Jefferson T.

    2014-01-01

    As part of the NOAA ECOHAB funded Gulf of Maine Toxicity (GOMTOX)1 project, we determined Alexandrium fundyense abundance, paralytic shellfish poisoning (PSP) toxin composition, and concentration in quantitatively-sampled size-fractionated (20–64, 64–100, 100–200, 200–500, and > 500 μm) particulate water samples, and the community composition of potential grazers of A. fundyense in these size fractions, at multiple depths (typically 1, 10, 20 m, and near-bottom) during 10 large-scale sampling cruises during the A. fundyense bloom season (May–August) in the coastal Gulf of Maine and on Georges Bank in 2007, 2008, and 2010. Our findings were as follows: (1) when all sampling stations and all depths were summed by year, the majority (94% ± 4%) of total PSP toxicity was contained in the 20–64 μm size fraction; (2) when further analyzed by depth, the 20–64 μm size fraction was the primary source of toxin for 97% of the stations and depths samples over three years; (3) overall PSP toxin profiles were fairly consistent during the three seasons of sampling with gonyautoxins (1, 2, 3, and 4) dominating (90.7% ± 5.5%), followed by the carbamate toxins saxitoxin (STX) and neosaxitoxin (NEO) (7.7% ± 4.5%), followed by n-sulfocarbamoyl toxins (C1 and 2, GTX5) (1.3% ± 0.6%), followed by all decarbamoyl toxins (dcSTX, dcNEO, dcGTX2&3) (< 1%), although differences were noted between PSP toxin compositions for nearshore coastal Gulf of Maine sampling stations compared to offshore Georges Bank sampling stations for 2 out of 3 years; (4) surface cell counts of A. fundyense were a fairly reliable predictor of the presence of toxins throughout the water column; and (5) nearshore surface cell counts of A. fundyense in the coastal Gulf of Maine were not a reliable predictor of A. fundyense populations offshore on Georges Bank for 2 out of the 3 years sampled. PMID:25076816

  18. Toxicity assessment for RMA target contaminants. Volume 1. Endangerment assessment RMA, task 35. Final draft report

    SciTech Connect

    1987-06-01

    This report is detailed discussion of the evaluations performed to develop the toxicity assessment for RMA contaminants in soil. The objectives of the toxicity assessment are to determine the nature and extent of health and environmental hazards associated with exposure to contaminants present at the site and identify a quantitative index of toxicity for each target contaminant, referred to in this assessment as DT. The toxicity assessment for the RMA target contaminants has been performed consistent with published EPA guidelines and addresses only human health hazards associated with contaminants in soil. Each toxicity profile is composed of seven sections: 1. summary; 2. chemical and physical properties; and 3. transport and rate.

  19. 48 CFR 3011.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Market acceptance. 3011.103 Section 3011.103 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... Developing Requirements Documents 3011.103 Market acceptance. (a) Contracting officers may act on behalf...

  20. 7 CFR 930.26 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 930.26 Section 930.26 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Administrative Body § 930.26 Acceptance. Each person to be appointed by the Secretary as a member or as...

  1. 48 CFR 2811.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Market acceptance. 2811.103 Section 2811.103 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE COMPETITION AND... acceptance. Pursuant to FAR 11.103, the HCA or designee at a level not lower than the BPC has the...

  2. 48 CFR 1311.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Market acceptance. 1311.103 Section 1311.103 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE COMPETITION AND... acceptance. The designee authorized as the head of the agency is set forth in CAM 1301.70....

  3. 36 CFR 251.62 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 2 2011-07-01 2011-07-01 false Acceptance. 251.62 Section 251.62 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE LAND USES Special Uses § 251.62 Acceptance. Except for an easement, a special use authorization shall become...

  4. 48 CFR 3011.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Market acceptance. 3011.103 Section 3011.103 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... Developing Requirements Documents 3011.103 Market acceptance. (a) Contracting officers may act on behalf...

  5. 48 CFR 1011.103 - Market Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Market Acceptance. 1011.103 Section 1011.103 Federal Acquisition Regulations System DEPARTMENT OF THE TREASURY COMPETITION AND... Acceptance. (a) BCPOs can act on behalf of the head of the agency in this subpart only. BCPOs,...

  6. 7 CFR 916.25 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 916.25 Section 916.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Administrative Body § 916.25 Acceptance. Each person to be selected by the Secretary as...

  7. 43 CFR 3452.1-3 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Acceptance. 3452.1-3 Section 3452.1-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT..., Cancellation, and Termination § 3452.1-3 Acceptance. The effective date of the lease relinquishment shall,...

  8. 48 CFR 1311.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Market acceptance. 1311.103 Section 1311.103 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE COMPETITION AND... acceptance. The designee authorized as the head of the agency is set forth in CAM 1301.70....

  9. 7 CFR 916.25 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 916.25 Section 916.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Administrative Body § 916.25 Acceptance. Each person to be selected by the Secretary as...

  10. 7 CFR 920.25 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 920.25 Section 920.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Administrative Body § 920.25 Acceptance. Each person to be selected by the Secretary as a member or as...

  11. 5 CFR 1655.11 - Loan acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... CFR 1653.3(c); or (f) The participant has received a taxable loan distribution from the TSP within the... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Loan acceptance. 1655.11 Section 1655.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD LOAN PROGRAM § 1655.11 Loan acceptance....

  12. 7 CFR 930.26 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 930.26 Section 930.26 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Administrative Body § 930.26 Acceptance. Each person to be appointed by the Secretary as a member or as...

  13. 7 CFR 945.27 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 945.27 Section 945.27 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... § 945.27 Acceptance. Any person nominated to serve on the committee as a member or as an alternate...

  14. 19 CFR 114.21 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Acceptance. 114.21 Section 114.21 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARNETS Processing of Carnets § 114.21 Acceptance. A carnet executed in accordance with § 114.3 shall...

  15. 19 CFR 114.21 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Acceptance. 114.21 Section 114.21 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARNETS Processing of Carnets § 114.21 Acceptance. A carnet executed in accordance with § 114.3 shall...

  16. 7 CFR 920.25 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 920.25 Section 920.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Administrative Body § 920.25 Acceptance. Each person to be selected by the Secretary as a member or as...

  17. 7 CFR 932.32 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 932.32 Section 932.32 Agriculture... Regulating Handling Olive Administrative Committee § 932.32 Acceptance. Any person selected by the Secretary as a member or as an alternate member of the committee shall qualify by filing a written...

  18. 5 CFR 1655.11 - Loan acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... CFR 1653.3(c); or (f) The participant has received a taxable loan distribution from the TSP within the... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Loan acceptance. 1655.11 Section 1655.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD LOAN PROGRAM § 1655.11 Loan acceptance....

  19. 48 CFR 411.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Market acceptance. 411.103 Section 411.103 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE COMPETITION AND... acceptance. (a) The head of the contracting activity (HCA) may determine that offerors must demonstrate,...

  20. 7 CFR 989.32 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 989.32 Section 989.32 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... CALIFORNIA Order Regulating Handling Raisin Administrative Committee § 989.32 Acceptance. Each person to...

  1. 7 CFR 932.32 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 932.32 Section 932.32 Agriculture... Regulating Handling Olive Administrative Committee § 932.32 Acceptance. Any person selected by the Secretary as a member or as an alternate member of the committee shall qualify by filing a written...

  2. 7 CFR 945.27 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 945.27 Section 945.27 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... § 945.27 Acceptance. Any person nominated to serve on the committee as a member or as an alternate...

  3. 48 CFR 411.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Market acceptance. 411.103 Section 411.103 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE COMPETITION AND... acceptance. (a) The head of the contracting activity (HCA) may determine that offerors must demonstrate,...

  4. 36 CFR 251.62 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Acceptance. 251.62 Section 251.62 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE LAND USES Special Uses § 251.62 Acceptance. Except for an easement, a special use authorization shall become...

  5. 49 CFR 193.2303 - Construction acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Construction acceptance. 193.2303 Section 193.2303 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Construction § 193.2303 Construction acceptance. No person may place in...

  6. 49 CFR 193.2303 - Construction acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Construction acceptance. 193.2303 Section 193.2303 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Construction § 193.2303 Construction acceptance. No person may place in...

  7. Why Do Women Accept the Rape Myth?

    ERIC Educational Resources Information Center

    Tabone, Christopher; And Others

    The rape myth, defined as prejudicial, stereotyped, or false beliefs about rape, rape victims, and rapists, is accepted by individuals from varied walks of life, including women. It has been suggested that rape myth acceptance (RMA) among women serves a protective function by enabling women to dissociate themselves from a rape victim's experience.…

  8. Heavy Metal, Religiosity, and Suicide Acceptability.

    ERIC Educational Resources Information Center

    Stack, Steven

    1998-01-01

    Reports on data taken from the General Social Survey that found a link between "heavy metal" rock fanship and suicide acceptability. Finds that relationship becomes nonsignificant once level of religiosity is controlled. Heavy metal fans are low in religiosity, which contributes to greater suicide acceptability. (Author/JDM)

  9. Nevada Test Site Waste Acceptance Criteria (NTSWAC)

    SciTech Connect

    NNSA /NSO Waste Management Project

    2008-06-01

    This document establishes the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office, Nevada Test Site Waste Acceptance Criteria (NTSWAC). The NTSWAC provides the requirements, terms, and conditions under which the Nevada Test Site will accept low-level radioactive (LLW) and LLW Mixed Waste (MW) for disposal.

  10. 48 CFR 411.103 - Market acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Market acceptance. 411.103... ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 411.103 Market... accordance with FAR 11.103(a), the market acceptability of their items to be offered. (b) The...

  11. 48 CFR 411.103 - Market acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Market acceptance. 411.103... ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 411.103 Market... accordance with FAR 11.103(a), the market acceptability of their items to be offered. (b) The...

  12. 48 CFR 3011.103 - Market acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Market acceptance. 3011.103 Section 3011.103 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY... Requirements Documents 3011.103 Market acceptance. (a) Contracting officers may act on behalf of the head...

  13. 48 CFR 411.103 - Market acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Market acceptance. 411.103... ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 411.103 Market... accordance with FAR 11.103(a), the market acceptability of their items to be offered. (b) The...

  14. 48 CFR 3011.103 - Market acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Market acceptance. 3011.103 Section 3011.103 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... Developing Requirements Documents 3011.103 Market acceptance. (a) Contracting officers may act on behalf...

  15. 48 CFR 3011.103 - Market acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Market acceptance. 3011.103 Section 3011.103 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... Developing Requirements Documents 3011.103 Market acceptance. (a) Contracting officers may act on behalf...

  16. Four therapeutic diets: adherence and acceptability.

    PubMed

    Berkow, Susan E; Barnard, Neal; Eckart, Jill; Katcher, Heather

    2010-01-01

    Many health conditions are treated, at least in part, by therapeutic diets. Although the success of any intervention depends on its acceptability to the patient, the acceptability of therapeutic diets and factors that influence it have been largely neglected in nutrition research. A working definition of acceptability is proposed and an examination and summary are provided of available data on the acceptability of common diet regimens used for medical conditions. The goal is to suggest ways to improve the success of therapeutic diets. The proposed working definition of "acceptability" refers to the user's judgment of the advantages and disadvantages of a therapeutic diet-in relation to palatability, costs, and effects on eating behaviour and health-that influence the likelihood of adherence. Very low-calorie, reduced-fat omnivorous, vegetarian and vegan, and low-carbohydrate diets all achieve acceptability among the majority of users in studies of up to one year, in terms of attrition and adherence rates and results of questionnaires assessing eating behaviours. Longer studies are fewer, but they suggest that vegetarian, vegan, and reduced-fat diets are acceptable, as indicated by sustained changes in nutrient intake. Few studies of this length have been published for very low-calorie or low-carbohydrate diets. Long-term studies of adherence and acceptability of these and other therapeutic diets are warranted. PMID:21144137

  17. Improving Acceptance of Automated Counseling Procedures.

    ERIC Educational Resources Information Center

    Johnson, James H.; And Others

    This paper discusses factors that may influence the acceptance of automated counseling procedures by the military. A consensual model of the change process is presented which structures organizational readiness, the change strategy, and acceptance as integrated variables to be considered in a successful installation. A basic introduction to the…

  18. Enzyme Reactions and Acceptability of Plant Foods.

    ERIC Educational Resources Information Center

    Palmer, James K.

    1984-01-01

    Provides an overview of enzyme reactions which contribute to the character and acceptability of plant foods. A detailed discussion of polyphenoloxidase is also provided as an example of an enzyme which can markedly affect the character and acceptability of such foods. (JN)

  19. 49 CFR 193.2303 - Construction acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...: FEDERAL SAFETY STANDARDS Construction § 193.2303 Construction acceptance. No person may place in service... 49 Transportation 3 2010-10-01 2010-10-01 false Construction acceptance. 193.2303 Section 193.2303 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS...

  20. 34 CFR 668.57 - Acceptable documentation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Acceptable documentation. 668.57 Section 668.57... Application Information § 668.57 Acceptable documentation. (a) Adjusted Gross Income (AGI), income earned from... applicant, the documentation set forth in paragraph (a)(4) of this section if the individual for the...

  1. The acceptability of ending a patient's life

    PubMed Central

    Guedj, M; Gibert, M; Maudet, A; Munoz, S; Mullet, E; Sorum, P

    2005-01-01

    Objectives: To clarify how lay people and health professionals judge the acceptability of ending the life of a terminally ill patient. Design: Participants judged this acceptability in a set of 16 scenarios that combined four factors: the identity of the actor (patient or physician), the patient's statement or not of a desire to have his life ended, the nature of the action as relatively active (injecting a toxin) or passive (disconnecting life support), and the type of suffering (intractable physical pain, complete dependence, or severe psychiatric illness). Participants: 115 lay people and 72 health professionals (22 nurse's aides, 44 nurses, six physicians) in Toulouse, France. Main measurements: Mean acceptability ratings for each scenario for each group. Results: Life ending interventions are more acceptable to lay people than to the health professionals. For both, acceptability is highest for intractable physical suffering; is higher when patients end their own lives than when physicians do so; and, when physicians are the actors, is higher when patients have expressed a desire to die (voluntary euthanasia) than when they have not (involuntary euthanasia). In contrast, when patients perform the action, acceptability for the lay people and nurse's aides does not depend on whether the patient has expressed a desire to die, while for the nurses and physicians unassisted suicide is more acceptable than physician assisted suicide. Conclusions: Lay participants judge the acceptability of life ending actions in largely the same way as do healthcare professionals. PMID:15923476

  2. Consumer acceptance of ginseng food products.

    PubMed

    Chung, Hee Sook; Lee, Young-Chul; Rhee, Young Kyung; Lee, Soo-Yeun

    2011-01-01

    Ginseng has been utilized less in food products than in dietary supplements in the United States. Sensory acceptance of ginseng food products by U.S. consumers has not been reported. The objectives of this study were to: (1) determine the sensory acceptance of commercial ginseng food products and (2) assess influence of the addition of sweeteners to ginseng tea and ginseng extract to chocolate on consumer acceptance. Total of 126 consumers participated in 3 sessions for (1) 7 commercial red ginseng food products, (2) 10 ginseng teas varying in levels of sugar or honey, and (3) 10 ginseng milk or dark chocolates varying in levels of ginseng extract. Ginseng candy with vitamin C and ginseng crunchy white chocolate were the most highly accepted, while sliced ginseng root product was the least accepted among the seven commercial products. Sensory acceptance increased in proportion to the content of sugar and honey in ginseng tea, whereas acceptance decreased with increasing content of ginseng extract in milk and dark chocolates. Findings demonstrate that ginseng food product types with which consumers have been already familiar, such as candy and chocolate, will have potential for success in the U.S. market. Chocolate could be suggested as a food matrix into which ginseng can be incorporated, as containing more bioactive compounds than ginseng tea at a similar acceptance level. Future research may include a descriptive analysis with ginseng-based products to identify the key drivers of liking and disliking for successful new product development. PMID:22416723

  3. A Distributive Model of Treatment Acceptability

    ERIC Educational Resources Information Center

    Carter, Stacy L.

    2008-01-01

    A model of treatment acceptability is proposed that distributes overall treatment acceptability into three separate categories of influence. The categories are comprised of societal influences, consultant influences, and influences associated with consumers of treatments. Each of these categories are defined and their inter-relationships within…

  4. 40 CFR 161.70 - Acceptable protocols.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Acceptable protocols. 161.70 Section 161.70 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR REGISTRATION OF ANTIMICROBIAL PESTICIDES General Provisions § 161.70 Acceptable protocols....

  5. 40 CFR 161.70 - Acceptable protocols.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Acceptable protocols. 161.70 Section 161.70 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR REGISTRATION OF ANTIMICROBIAL PESTICIDES General Provisions § 161.70 Acceptable protocols....

  6. The ethical and practical aspects of acceptance and universal patient acceptance.

    PubMed

    Corsino, Bruce V; Patthoff, Donald E

    2006-11-01

    "Acceptance" is an often presupposed, hidden core value and ethic focused on how dental and other health practitioners first accept people as possible patients. The three basic styles of patient acceptance are random, selective, and universal. Reduced public access to care results from the practice of random and selective acceptance. Only universal acceptance creates a potential pathway for improved access to care. The notion of Universal Patient Acceptance (UPA) is discussed here as one kind of applied ethical tool or clinical practice that allows for the ethic of acceptance to be more effectively pursued in daily practice. We suggest that health providers falsely surmise that they already understand and practice Universal Patient Acceptance. That myth and perspective are partly what keeps Acceptance hidden as an ethic and overlooked as a potential way to foster dialogue and indirectly promote better access to care. Without Universal Patient Acceptance, dental and health providers will continue to silently engage in practice patterns that adversely affect public access to care. The actual benefits of Universal Patient Acceptance are the subject of ongoing review and debate. Whatever those benefits might be will not likely be realized until Acceptance and Universal Patient Acceptance are included as part of dental and other health professional codes of ethics and training curricula. That is what we argue for here. PMID:17106034

  7. The toxicity of refrigerants

    SciTech Connect

    Calm, J.M.

    1996-07-01

    This paper presents toxicity data and exposure limits for refrigerants. The data address both acute (short-term, single exposure) and chronic (long-term, repeated exposure) effects, with emphasis on the former. The refrigerants covered include those in common use for the last decade, those used as components in alternatives, and selected candidates for future replacements. The paper also reviews the toxicity indicators used in both safety standards and building, mechanical, and fire codes. It then outlines current classification methods for refrigerant safety and relates them to standard and code usage.

  8. Toxic and Metabolic Myelopathies.

    PubMed

    Ramalho, Joana; Nunes, Renato Hoffmann; da Rocha, Antonio José; Castillo, Mauricio

    2016-10-01

    Myelopathy describes any neurologic deficit related to the spinal cord. It is most commonly caused by its compression by neoplasms, degenerative disc disease, trauma, or infection. Less common causes of myelopathy include spinal cord tumors, infection, inflammatory, neurodegenerative, vascular, toxic, and metabolic disorders. Conditions affecting the spinal cord must be recognized as early as possible to prevent progression that may lead to permanent disability. Biopsy is rarely performed, thus the diagnosis and management rely on patient׳s history, physical examination, laboratory results, and imaging findings. Here we review the clinical presentations, pathophysiological mechanisms, and magnetic resonance imaging findings of myelopathies related to metabolic or toxic etiologies. PMID:27616316

  9. Modeling of the charge acceptance of lead-acid batteries

    NASA Astrophysics Data System (ADS)

    Thele, M.; Schiffer, J.; Karden, E.; Surewaard, E.; Sauer, D. U.

    This paper presents a model for flooded and VRLA batteries that is parameterized by impedance spectroscopy and includes the overcharging effects to allow charge-acceptance simulations (e.g. for regenerative-braking drive-cycle profiles). The full dynamic behavior and the short-term charge/discharge history is taken into account. This is achieved by a detailed modeling of the sulfate crystal growth and modeling of the internal gas recombination cycle. The model is applicable in the full realistic temperature and current range of automotive applications. For model validation, several load profiles (covering the dynamics and the current range appearing in electrically assisted or hybrid cars) are examined and the charge-acceptance limiting effects are elaborately discussed. The validation measurements have been performed for different types of lead-acid batteries (flooded and VRLA). The model is therefore an important tool for the development of automotive power nets, but it also allows to analyze different charging strategies and energy gains which can be achieved during regenerative-braking.

  10. Toxicity assessment through multiple endpoint bioassays in soils posing environmental risk according to regulatory screening values.

    PubMed

    Rodriguez-Ruiz, A; Asensio, V; Zaldibar, B; Soto, M; Marigómez, I

    2014-01-01

    Toxicity profiles of two soils (a brownfield in Legazpi and an abandoned iron mine in Zugaztieta; Basque Country) contaminated with several metals (As, Zn, Pb and Cu in Legazpi; Zn, Pb, Cd and Cu in Zugaztieta) and petroleum hydrocarbons (in Legazpi) were determined using a multi-endpoint bioassay approach. Investigated soils exceeded screening values (SVs) of regulatory policies in force (Basque Country; Europe). Acute and chronic toxicity bioassays were conducted with a selected set of test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates, as well as with bioaccumulation studies in earthworms. The sensitivity of the test species and the toxicity endpoints varied depending on the soil. It was concluded that whilst Zugaztieta soil showed very little or no toxicity, Legazpi soil was toxic according to almost all the toxicity tests (solid phase Microtox, D. discoideum inhibition of fruiting body formation and developmental cycle solid phase assays, lettuce seed germination and root elongation test, earthworm acute toxicity and reproduction tests, D. discoideum cell viability and replication elutriate assays). Thus, albeit both soils had similar SVs, their ecotoxicological risk, and therefore the need for intervening, was different for each soil as unveiled after toxicity profiling based on multiple endpoint bioassays. Such a toxicity profiling approach is suitable to be applied for scenario-targeted soil risk assessment in those cases where applicable national/regional soil legislation based on SVs demands further toxicity assessment. PMID:24819436

  11. Toxicity of azaarenes.

    PubMed

    Bleeker, Eric A J; Wiegman, Saskia; de Voogt, Pim; Kraak, Michiel; Leslie, Heather A; de Haas, Elske; Admiraal, Wim

    2002-01-01

    Heterocyclic compounds by far outnumber the homocyclic PAHs. In addition, they are often more soluble in water, which may imply a greater biological significance of these heterocycles. Yet, most research focuses on the homocyclics, based on the implicit assumption that the mostly higher concentration of the homocyclics rank these compounds as priority compounds. This review critically examines the available evidence and poses questions on the biological activity and environmental risk of one small group of heterocyclics, the azaarenes, which contain one nitrogen atom in one of the aromatic rings. In different sections, the biotransformation and different types of toxicity are discussed in comparison to those of homocyclic PAHs. The last section focuses on the implications for risk assessment of PAHs. Two- and three-ringed azaarenes can be relatively easily transformed by bacteria, fungi, invertebrates, and vertebrates. The presence of the N-moiety in the smaller azaarenes leads to metabolic routes that partly differ from those of the homoaromatic analogues. Major metabolic products of the azaarenes appear to be ketones and mono- or dihydroxylated azaarenes. Microorganisms can further degrade these into multiple oxygen-containing compounds or they can open up the aza-containing aromatic ring and fully metabolize the products. Fungi and vertebrates were shown to produce the mutagenic dihydrodiol metabolites. The metabolism of the larger azaarenes in vertebrates proceeds analogous to homoaromatic PAH, because in these larger molecules the N-moiety has less influence. Transformation of the larger azaarenes by microorganisms proceeds much slower if occurring at all. Direct toxicity data of azaarenes are mostly restricted to the effects of acridine and quinoline on a relatively small number of species. From this limited set it becomes clear that differences between species are relatively small. As with homocyclic PAHs, toxicity generally increases with increasing number

  12. Acceptance threshold hypothesis is supported by chemical similarity of cuticular hydrocarbons in a stingless bee, Melipona asilvai.

    PubMed

    Nascimento, D L; Nascimento, F S

    2012-11-01

    The ability to discriminate nestmates from non-nestmates in insect societies is essential to protect colonies from conspecific invaders. The acceptance threshold hypothesis predicts that organisms whose recognition systems classify recipients without errors should optimize the balance between acceptance and rejection. In this process, cuticular hydrocarbons play an important role as cues of recognition in social insects. The aims of this study were to determine whether guards exhibit a restrictive level of rejection towards chemically distinct individuals, becoming more permissive during the encounters with either nestmate or non-nestmate individuals bearing chemically similar profiles. The study demonstrates that Melipona asilvai (Hymenoptera: Apidae: Meliponini) guards exhibit a flexible system of nestmate recognition according to the degree of chemical similarity between the incoming forager and its own cuticular hydrocarbons profile. Guards became less restrictive in their acceptance rates when they encounter non-nestmates with highly similar chemical profiles, which they probably mistake for nestmates, hence broadening their acceptance level. PMID:23053920

  13. Mercury toxicity and neurodegenerative effects.

    PubMed

    Carocci, Alessia; Rovito, Nicola; Sinicropi, Maria Stefania; Genchi, Giuseppe

    2014-01-01

    Mercury is among the most toxic heavy metals and has no known physiological role in humans. Three forms of mercury exist: elemental, inorganic and organic. Mercury has been used by man since ancient times. Among the earliest were the Chinese and Romans, who employed cinnabar (mercury sulfide) as a red dye in ink (Clarkson et al. 2007). Mercury has also been used to purify gold and silver minerals by forming amalgams. This is a hazardous practice, but is still widespread in Brazil's Amazon basin, in Laos and in Venezuela, where tens of thousands of miners are engaged in local mining activities to find and purify gold or silver. Mercury compounds were long used to treat syphilis and the element is still used as an antiseptic,as a medicinal preservative and as a fungicide. Dental amalgams, which contain about 50% mercury, have been used to repair dental caries in the U.S. since 1856.Mercury still exists in many common household products around the world.Examples are: thermometers, barometers, batteries, and light bulbs (Swain et al.2007). In small amounts, some organo mercury-compounds (e.g., ethylmercury tiosalicylate(thimerosal) and phenylmercury nitrate) are used as preservatives in some medicines and vaccines (Ballet al. 2001).Each mercury form has its own toxicity profile. Exposure to Hg0 vapor and MeHg produce symptoms in CNS, whereas, the kidney is the target organ when exposures to the mono- and di-valent salts of mercury (Hg+ and Hg++, respectively)occur. Chronic exposure to inorganic mercury produces stomatitis, erethism and tremors. Chronic MeHg exposure induced symptoms similar to those observed in ALS, such as the early onset of hind limb weakness (Johnson and Atchison 2009).Among the organic mercury compounds, MeHg is the most biologically available and toxic (Scheuhammer et a!. 2007). MeHg is neurotoxic, reaching high levels of accumulation in the CNS; it can impair physiological function by disrupting endocrine glands (Tan et a!. 2009).The most

  14. DETROIT AIR TOXICS INITIATIVE

    EPA Science Inventory

    The project will include both a risk assessment and a risk reduction component. The assessment component will capitalize on the strong air toxics database that currently exists for the Detroit area. Data from several monitoring studies/projects will be utilized to characterize ...

  15. MICROBIAL TOXICITY STUDIES

    EPA Science Inventory

    The chapter cites examples of the common methods used to determine the toxicity of chemicals to bacteria. It covers only the most common methods, particularly those that are easy to perform. Numerous literature citations have been included to help illustrate how a method is used ...

  16. NEW HAVEN TOXICS INVENTORY

    EPA Science Inventory

    EPA will be working with the New Haven Department of Health to collect data and create an inventory of toxic air pollutants in the New Haven area. Under section 112 of the Clean Air Act, EPA and cities and states are required to reduce cancer and non-cancer health risks in urb...

  17. Productivity in Toxicity Papers

    ERIC Educational Resources Information Center

    Montgomery, Ruth Reinke

    1973-01-01

    Personal bibliographies were obtained through a survey of the members of the Society of Toxicology. A group of 183 members showed a 16 percent increase in document output during 1968-1969 compared to 1960-1967. During 1960-1969, 221 members published or made available 1873 documents containing original toxicity data. (5 references) (Author)

  18. Quebec's Toxic Pollution Concern.

    ERIC Educational Resources Information Center

    Mingie, Walter

    The best solution to the problems of increased pollution of Quebec lakes and rivers with toxic wastes and increased incidence of pollution related diseases is to educate children, to make them aware of the environment and man's interrelationship with it. Attitudes of concern, based on knowledge, must be developed so that as adults, they will take…

  19. ToxCast: Developing Predictive Signatures of Chemically Induced Toxicity (S)

    EPA Science Inventory

    ToxCast, the United States Environmental Protection Agency’s chemical prioritization research program, is developing methods for utilizing computational chemistry, bioactivity profiling and toxicogenomic data to predict potential for toxicity and prioritize limited testing resour...

  20. Preliminary studies on model development for rodent toxicity and its interspecies correlation with aquatic toxicities of pharmaceuticals.

    PubMed

    Das, Rudra Narayan; Sanderson, Hans; Mwambo, Andrew E; Roy, Kunal

    2013-03-01

    Environmental toxicity due to pharmaceuticals has been an issue of serious concern for long time. Development of chemometric models with reliable predictive power has been considered as an effective tool for the design of new drug agents with reduced or without ecotoxic potential. Considering a higher degree of similarity in genetic homology towards drug receptor with mammals, we have used a dataset of 194 compounds with reported rodent, fish, daphnia and algae toxicity data for extrapolation of their toxicity towards humans. Allowing for rodents as the most surrogate to human physiology, attempts have also been made to develop interspecies correlation models keeping rodent toxicity as dependent variable so that any drug without reported rodent toxicity can be predicted using fish, daphnia or algae toxicity data which can be consequently extrapolated to human toxicity. The developed models have been subjected to multiple validation strategies. Acceptable results have been obtained in both cases of direct and interspecies extrapolation quantitative structure-activity relationship models. PMID:23238824

  1. Zeaxanthin: Review of Toxicological Data and Acceptable Daily Intake

    PubMed Central

    Edwards, James A.

    2016-01-01

    Zeaxanthin is a nutritional carotenoid with a considerable amount of safety data based on regulatory studies, which form the basis of its safety evaluation. Subchronic OECD guideline studies with mice and rats receiving beadlet formulations of high purity synthetic zeaxanthin in the diet at dosages up to 1000 mg/kg body weight (bw)/day, and in dogs at over 400 mg/kg bw/day, produced no adverse effects or histopathological changes. In developmental toxicity studies, there was no evidence of fetal toxicity or teratogenicity in rats or rabbits at dosages up to 1000 or 400 mg/kg bw/day, respectively. Formulated zeaxanthin was not mutagenic or clastogenic in a series of in vitro and in vivo tests for genotoxicity. A 52-week chronic oral study in Cynomolgus monkeys at doses of 0.2 and 20 mg/kg bw/day, mainly designed to assess accumulation and effects in primate eyes, showed no adverse effects. In a rat two-generation study, the NOAEL was 150 mg/kg bw/day. In 2012, this dosage was used by EFSA (NDA Panel), in association with a 200-fold safety factor, to propose an Acceptable Daily Intake equivalent to 53 mg/day for a 70 kg adult. The requested use level of 2 mg/day was ratified by the EU Commission. PMID:26885380

  2. Zeaxanthin: Review of Toxicological Data and Acceptable Daily Intake.

    PubMed

    Edwards, James A

    2016-01-01

    Zeaxanthin is a nutritional carotenoid with a considerable amount of safety data based on regulatory studies, which form the basis of its safety evaluation. Subchronic OECD guideline studies with mice and rats receiving beadlet formulations of high purity synthetic zeaxanthin in the diet at dosages up to 1000 mg/kg body weight (bw)/day, and in dogs at over 400 mg/kg bw/day, produced no adverse effects or histopathological changes. In developmental toxicity studies, there was no evidence of fetal toxicity or teratogenicity in rats or rabbits at dosages up to 1000 or 400 mg/kg bw/day, respectively. Formulated zeaxanthin was not mutagenic or clastogenic in a series of in vitro and in vivo tests for genotoxicity. A 52-week chronic oral study in Cynomolgus monkeys at doses of 0.2 and 20 mg/kg bw/day, mainly designed to assess accumulation and effects in primate eyes, showed no adverse effects. In a rat two-generation study, the NOAEL was 150 mg/kg bw/day. In 2012, this dosage was used by EFSA (NDA Panel), in association with a 200-fold safety factor, to propose an Acceptable Daily Intake equivalent to 53 mg/day for a 70 kg adult. The requested use level of 2 mg/day was ratified by the EU Commission. PMID:26885380

  3. Patent profiles

    SciTech Connect

    Not Available

    1980-01-01

    This report presents profiles of US patents in the area of solar energy technology, and in the related areas of wind, geothermal and tide and wave energy. Each profile is divided into three parts. The first part identifies the area which is examined, lists the pertinent US Patent Classification(s), and graphically illustrates patent activity across a designated 10-year span. The second part tabulates the data upon which the graphs of the first part were based, provides a list of assignees for the period 1969 to 1978 both by the number of patents and alphabetically, and presents on alphabetical listing of inventors of unassigned patents. The third part updates the preceding material for the period January-October 1979. (SPH)

  4. Comparing toxic air pollutant programs

    SciTech Connect

    Hawkins, S.C.

    1997-05-01

    This article compares state and federal toxic air pollutant programs. The Clean Air Act Ammendments created a program for the control of Hazardous Air Pollutants based on the establishment of control technology standards. State toxic programs can be classified into two categories: control technology-based and ambient concentration-based. Many states have opened to implement the MACT standards while enforcing their own state air toxics programs. Specific topics discussed include the following: the Federal air toxics program; existing state regulations; New Jersey Air Toxic Program; New York Toxics program.

  5. Consumer Acceptance of Dry Dog Food Variations

    PubMed Central

    Donfrancesco, Brizio Di; Koppel, Kadri; Swaney-Stueve, Marianne; Chambers, Edgar

    2014-01-01

    Simple Summary The objectives of this study were to compare the acceptance of different dry dog food products by consumers, determine consumer clusters for acceptance, and identify the characteristics of dog food that drive consumer acceptance. Pet owners evaluated dry dog food samples available in the US market. The results indicated that appearance of the sample, especially the color, influenced pet owner’s overall liking more than the aroma of the product. Abstract The objectives of this study were to compare the acceptance of different dry dog food products by consumers, determine consumer clusters for acceptance, and identify the characteristics of dog food that drive consumer acceptance. Eight dry dog food samples available in the US market were evaluated by pet owners. In this study, consumers evaluated overall liking, aroma, and appearance liking of the products. Consumers were also asked to predict their purchase intent, their dog’s liking, and cost of the samples. The results indicated that appearance of the sample, especially the color, influenced pet owner’s overall liking more than the aroma of the product. Overall liking clusters were not related to income, age, gender, or education, indicating that general consumer demographics do not appear to play a main role in individual consumer acceptance of dog food products. PMID:26480043

  6. Personality Factors Associated with the Decision to Accept or Reject Mobility Training.

    ERIC Educational Resources Information Center

    White, K.; And Others

    1990-01-01

    Adventitiously blind adults (n=79) who had accepted mobility training were compared to 60 subjects who had rejected training. Personality profiles varied significantly between groups on seven scales of the Minnesota Multiphasic Personality Inventory: psychasthenia; schizophrenia; psychopathic deviate; depression; hypomania; paranoia; and…

  7. Test systems to identify reproductive toxicants.

    PubMed

    Riecke, K; Stahlmann, R

    2000-09-01

    Experience with drugs and other xenobiotics indicates that both animal testing and epidemiological studies are necessary to provide adequate data for an estimation of risks that might be associated with exposure to a chemical substance. In this review, the pros and cons of test systems for reproductive toxicity are discussed. Usually, several studies are performed to cover the different phases of the reproductive cycle. In the preclinical development of drugs, the three so-called 'segment testing protocols' have been used for several decades now. More recently, new testing concepts have been accepted internationally which include more flexibility in implementation. Several examples of compounds with the potential for reproductive toxicity are presented in more detail in a discussion of some pitfalls of the tests for fertility (phthalates and fluoroquinolones), teratogenicity (acyclovir and protease inhibitors) and postnatal developmental toxicity (fluoroquinolones). In addition, important aspects of kinetics and metabolism as a prerequisite for a rational interpretation of results from toxicological studies are briefly discussed. In vitro assays are useful for supplementing the routinely used in vivo approaches or for studying an expected or defined effect, but they are not suitable for revealing an unknown effect of a chemical on the complex reproductive process. PMID:11021511

  8. Site planning considerations for toxic materials

    SciTech Connect

    Miller, G.

    1989-03-31

    We are developing procedures for controlling emergencies that may arise at sites where toxic materials are used. In our specific example, these materials are semiconductor gases such as phosphine, silane, chlorine, and diborane, but our procedures apply to other operations using toxic materials such as liquid-fueled rocket development and testing. We start by applying or developing Emergency Response Planning Guidelines (ERPGs) for the chemical of interest and we then determine trade offs between gas quantities and other precautions (such as stack heights or flow-limiting orifices) needed to keep ground-level concentrations acceptable during emergencies. We use a version of the widely acknowledged Gaussian-dispersion model (EPIcode) to estimate contaminant levels over 0.1 km from the release point, and we use an adaptation of Wilson's model to estimate concentrations nearer the source. We will discuss these procedures and other considerations (e.g., how we set ERPGs, the relation of ERPGs to other criteria such as Emergency Exposure Limits, and how minimum stack heights are determined) and areas of uncertainty. This paper focuses on planning for emergencies involving toxic materials, routine protection of employees and the public; the normal activities of industrial hygienists and environmental protection personnel are not discussed. 16 refs., 3 figs., 3 tabs.

  9. Estimation of toxicity using the Toxicity Estimation Software Tool (TEST)

    EPA Science Inventory

    Tens of thousands of chemicals are currently in commerce, and hundreds more are introduced every year. Since experimental measurements of toxicity are extremely time consuming and expensive, it is imperative that alternative methods to estimate toxicity are developed.

  10. Consumer acceptance of nutrigenomics-based personalised nutrition.

    PubMed

    Ronteltap, A; van Trijp, J C M; Renes, R J

    2009-01-01

    Nutrigenomics is a new and promising development in nutritional science which aims to understand the fundamental molecular processes affected by foods. Despite general agreement on its promise for better understanding diet-health relationships, less consensus exists among experts on the potential of spin-offs aimed at the consumer such as personalised nutrition. Research into consumer acceptance of such applications is scarce. The present study develops a set of key hypotheses on public acceptance of personalised nutrition and tests these in a representative sample of Dutch consumers. An innovative consumer research methodology is used in which consumers evaluate short films which are systematically varied scenarios for the future of personalised nutrition. Consumer evaluations of these films, which are pre-tested in a pilot study, allow a formal test of how consumer perceptions of personalised nutrition drive consumer acceptance and through which fundamental psychological processes these effects are mediated. Public acceptance is enhanced if consumers can make their genetic profile available free at their own choice, if the actual spin-off products provide a clearly recognisable advantage to the consumer, and are easy to implement into the daily routine. Consumers prefer communication on nutrigenomics and personalised nutrition by expert stakeholders to be univocal and aimed at building support with consumers and their direct environments for this intriguing new development. Additionally, an exploratory segmentation analysis indicated that people have different focal points in their preferences for alternative scenarios of personalised nutrition. The insights obtained from the present study provide guidance for the successful further development of nutrigenomics and its applications. PMID:18479587

  11. Organic Matter Application Can Reduce Copper Toxicity in Tomato Plants

    ERIC Educational Resources Information Center

    Campbell, Brian

    2010-01-01

    Copper fungicides and bactericides are often used in tomato cultivation and can cause toxic Cu levels in soils. In order to combat this, organic matter can be applied to induce chelation reactions and form a soluble complex by which much of the Cu can leach out of the soil profile or be taken up safely by plants. Organic acids such as citric,…

  12. Polycyclic aromatic hydrocarbons in Dalian soils: distribution and toxicity assessment.

    PubMed

    Wang, Zhen; Chen, Jingwen; Yang, Ping; Qiao, Xianliang; Tian, Fulin

    2007-02-01

    Concentrations of 15 polycyclic aromatic hydrocarbons (PAHs) were measured in surface soils collected from Dalian, China, for examination of distributions and composition profiles and their potential toxicity. The sum of 15 PAHs (SigmaPAHs) ranged from 190 to 8595 ng g(-1) dry weight, and showed an apparent urban-suburban-rural gradient in both SigmaPAHs and composition profiles. Using hierarchical cluster analysis (HCA), the sampling sites were grouped into four clusters corresponding to traffic area, park/residential area, suburban and rural areas. The ratios of naphthalene (Nap) and fluorene (Fl) versus fluoranthene (Flu), pyrene (Pyr) and indeno(1,2,3-cd)pyrene (InP) in the four clusters provided evidence of local distillation. The diagnostic ratios indicated the prevalent PAH sources were petroleum combustion and coal combustion in Dalian, and a cross plot of diagnostic ratios distinguished the urban samples from suburban and rural ones. Toxic potency assessment of soil PAHs presented a good relationship with benzo(a)pyrene (BaP) levels, toxic equivalent concentrations based on BaP (TEQ(BaP)) and dioxin-like toxic equivalent concentrations (TEQ(TCDD)). The study highlights that BaP is a good indicator for assessing the potential toxicity of PAHs, and presents a promising toxicity assessment method for soil PAHs. PMID:17285163

  13. Approaches to acceptable risk: a critical guide

    SciTech Connect

    Fischhoff, B.; Lichtenstein, S.; Slovic, P.; Keeney, R.; Derby, S.

    1980-12-01

    Acceptable-risk decisions are an essential step in the management of technological hazards. In many situations, they constitute the weak (or missing) link in the management process. The absence of an adequate decision-making methodology often produces indecision, inconsistency, and dissatisfaction. The result is neither good for hazard management nor good for society. This report offers a critical analysis of the viability of various approaches as guides to acceptable-risk decisions. This report seeks to define acceptable-risk decisions and to examine some frequently proposed, but inappropriate, solutions. 255 refs., 22 figs., 25 tabs.

  14. Hanford Site Solid Waste Acceptance Criteria

    SciTech Connect

    Not Available

    1993-11-17

    This manual defines the Hanford Site radioactive, hazardous, and sanitary solid waste acceptance criteria. Criteria in the manual represent a guide for meeting state and federal regulations; DOE Orders; Hanford Site requirements; and other rules, regulations, guidelines, and standards as they apply to acceptance of radioactive and hazardous solid waste at the Hanford Site. It is not the intent of this manual to be all inclusive of the regulations; rather, it is intended that the manual provide the waste generator with only the requirements that waste must meet in order to be accepted at Hanford Site TSD facilities.

  15. NEVADA TEST SITE WASTE ACCEPTANCE CRITERIA

    SciTech Connect

    U.S. DEPARTMENT OF ENERGY, NATIONAL NUCLEAR SECURITY ADMINISTRATION, NEVADA SITE OFFICE

    2005-07-01

    This document establishes the U. S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) waste acceptance criteria (WAC). The WAC provides the requirements, terms, and conditions under which the Nevada Test Site will accept low-level radioactive and mixed waste for disposal. Mixed waste generated within the State of Nevada by NNSA/NSO activities is accepted for disposal. It includes requirements for the generator waste certification program, characterization, traceability, waste form, packaging, and transfer. The criteria apply to radioactive waste received at the Nevada Test Site Area 3 and Area 5 Radioactive Waste Management Site for storage or disposal.

  16. The alkaloid profiles of Lupinus sulphureus.

    PubMed

    Cook, Daniel; Lee, Stephen T; Gardner, Dale R; Pfister, James A; Welch, Kevin D; Green, Benedict T; Davis, T Zane; Panter, Kip E

    2009-02-25

    Lupines are common plants on the rangelands in the western United States. Lupines contain alkaloids that can be toxic and teratogenic causing congenital birth defects (crooked calf disease). One such lupine, Lupinus sulphureus, occurs in parts of Oregon, Washington, and British Columbia. Specimens of L. sulphureus from field collections and herbaria were evaluated taxonomically and by chemical means. A total of seven distinct alkaloid profiles and the individual alkaloids associated with each profile were identified. Each alkaloid profile was unique in its geographical distribution and its potential risk to livestock. In conclusion, taxonomic classification is not sufficient to determine risk, as chemical characterization of the alkaloids must also be performed. PMID:19182952

  17. Predictive models of prenatal developmental toxicity from ToxCast high-throughput screening data

    EPA Science Inventory

    EPA's ToxCast™ project is profiling the in vitro bioactivity of chemicals to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesized that developmental toxicity in guideline animal studies captured in the ToxRefDB database wou...

  18. Predictive Modeling of Developmental Toxicity

    EPA Science Inventory

    The use of alternative methods in conjunction with traditional in vivo developmental toxicity testing has the potential to (1) reduce cost and increase throughput of testing the chemical universe, (2) prioritize chemicals for further targeted toxicity testing and risk assessment,...

  19. Gas characterization system software acceptance test report

    SciTech Connect

    Vo, C.V.

    1996-03-28

    This document details the results of software acceptance testing of gas characterization systems. The gas characterization systems will be used to monitor the vapor spaces of waste tanks known to contain measurable concentrations of flammable gases.

  20. 7 CFR 1205.326 - Acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE COTTON RESEARCH AND PROMOTION Cotton Research and Promotion Order Cotton Board § 1205.326 Acceptance. Any person selected by the Secretary as...

  1. 7 CFR 1205.326 - Acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE COTTON RESEARCH AND PROMOTION Cotton Research and Promotion Order Cotton Board § 1205.326 Acceptance. Any person selected by the Secretary as...

  2. 7 CFR 989.32 - Acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN CALIFORNIA Order Regulating Handling Raisin Administrative Committee § 989.32 Acceptance. Each person to...

  3. 7 CFR 989.32 - Acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN CALIFORNIA Order Regulating Handling Raisin Administrative Committee § 989.32 Acceptance. Each person to...

  4. Integrated Model for E-Learning Acceptance

    NASA Astrophysics Data System (ADS)

    Ramadiani; Rodziah, A.; Hasan, S. M.; Rusli, A.; Noraini, C.

    2016-01-01

    E-learning is not going to work if the system is not used in accordance with user needs. User Interface is very important to encourage using the application. Many theories had discuss about user interface usability evaluation and technology acceptance separately, actually why we do not make it correlation between interface usability evaluation and user acceptance to enhance e-learning process. Therefore, the evaluation model for e-learning interface acceptance is considered important to investigate. The aim of this study is to propose the integrated e-learning user interface acceptance evaluation model. This model was combined some theories of e-learning interface measurement such as, user learning style, usability evaluation, and the user benefit. We formulated in constructive questionnaires which were shared at 125 English Language School (ELS) students. This research statistics used Structural Equation Model using LISREL v8.80 and MANOVA analysis.

  5. Gas characterization system software acceptance test procedure

    SciTech Connect

    Vo, C.V.

    1996-02-27

    This document details the Software Acceptance Testing of gas characterization systems. The gas characterization systems will be used to monitor the vapor spaces of waste tanks known to contain measurable concentrations of flammable gases.

  6. Nevada Test Site Waste Acceptance Criteria

    SciTech Connect

    U.S. Department of Energy, Nevada Operations Office, Waste Acceptance Criteria

    1999-05-01

    This document provides the requirements, terms, and conditions under which the Nevada Test Site will accept low-level radioactive and mixed waste for disposal; and transuranic and transuranic mixed waste for interim storage at the Nevada Test Site.

  7. What Are Acceptable Limits of Radiation?

    NASA Video Gallery

    Brad Gersey, lead research scientist at the Center for Radiation Engineering and Science for Space Exploration, or CRESSE, at Prairie View A&M University, describes the legal and acceptable limits ...

  8. The role of taste in food acceptance at the beginning of complementary feeding.

    PubMed

    Schwartz, Camille; Chabanet, Claire; Lange, Christine; Issanchou, Sylvie; Nicklaus, Sophie

    2011-09-26

    Introduction of solid foods is a major step in the establishment of eating behavior and is likely to affect children's health. However, the role of taste in acceptance of new foods, in particular in the first months of complementary feeding, is not fully understood and was the aim of the present study. Infants had to be in good health to participate (N=74). First, the infants' reactions to new foods were recorded by their parents between the ages of 5 and 7 months using a 4-point-scale ranging from very negative to very positive. Taste intensities of infant foods were scored by a trained panel and foods were clustered into groups showing similar taste profiles. Infants' reactions were used to calculate new food acceptance (NFA) defined as the average reaction towards a group of foods showing a similar taste profile. Second, preferences for the five basic tastes over water were measured using a 4-bottle test at 6 months old comparing intake of tastant solutions to water. Taste acceptance was evaluated through ingestion ratio (IR=intake of tastant solutions/intake of tastant solutions and water). NFAs were compared across food groups. Kendall correlations were calculated between NFA and IR. Most reactions (88%) to new foods were positive. However, NFA varied according to the taste profile of the foods: vegetables in which salt or a salty ingredient was added were more accepted than plain vegetables (P<0.01). On average no rejection of basic tastes was observed. For sweet, sour and umami tastes, significant positive correlations were observed between NFA and IR. Healthy foods like vegetables could be easily introduced in the diet of most, but not all infants. The role of taste preferences in new food acceptance was highlighted: a higher acceptance for a taste was associated to an enhanced acceptance of foods bearing this taste. PMID:21554893

  9. Generalized group chain acceptance sampling plan

    NASA Astrophysics Data System (ADS)

    Zain, Zakiyah; Mughal, Abdur Razzaque; Aziz, Nazrina

    2015-12-01

    In this article, we proposed an acceptance sampling plan based on generalized group chain truncated life test. The decision on acceptance of a submitted lot can be made by using the cumulative information of the immediately preceding samples. The design parameters of the proposed plan such as the minimum number of groups are found to satisfy the desired quality standard. The benefits of this plan include smaller sample size and reduced overall costs.

  10. Acceptance Test Plan for ANSYS Software

    SciTech Connect

    CREA, B.A.

    2000-10-25

    This plan governs the acceptance testing of the ANSYS software (Full Mechanical Release 5.5) for use on Project Word Management Contract (PHMC) computer systems (either UNIX or Microsoft Windows/NT). There are two phases to the acceptance testing covered by this test plan: program execution in accordance with the guidance provided in installation manuals; and ensuring results of the execution are consistent with the expected physical behavior of the system being modeled.

  11. Update on toxic myopathies.

    PubMed

    Mastaglia, F L; Needham, M

    2012-02-01

    The toxic myopathies are a clinically and pathologically diverse group of disorders that can be caused by a variety of therapeutic agents used in clinical practice, as well as various venoms and other biological toxins. The most important iatrogenic causes are the statin and fibrate cholesterol-lowering agents that can cause a severe necrotizing myopathy and acute rhabdomyolysis and myoglobinuria. The current update focuses on the mechanisms of statin myotoxicity and the importance of genetic predisposing factors for statin myopathy, as well as the recently described form of necrotizing autoimmune myopathy, which is associated with antibodies to the 3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme and is responsive to aggressive immunotherapy. Mitochondrial myopathies associated with antiretroviral agents and the pyrimidine nucleoside analogue clevudine, and recent reports of myopathies caused by ingestion of red yeast rice and toxic species of mushrooms are also discussed. PMID:21968786

  12. Tungsten Toxicity in Plants

    PubMed Central

    Adamakis, Ioannis-Dimosthenis S.; Panteris, Emmanuel; Eleftheriou, Eleftherios P.

    2012-01-01

    Tungsten (W) is a rare heavy metal, widely used in a range of industrial, military and household applications due to its unique physical properties. These activities inevitably have accounted for local W accumulation at high concentrations, raising concerns about its effects for living organisms. In plants, W has primarily been used as an inhibitor of the molybdoenzymes, since it antagonizes molybdenum (Mo) for the Mo-cofactor (MoCo) of these enzymes. However, recent advances indicate that, beyond Mo-enzyme inhibition, W has toxic attributes similar with those of other heavy metals. These include hindering of seedling growth, reduction of root and shoot biomass, ultrastructural malformations of cell components, aberration of cell cycle, disruption of the cytoskeleton and deregulation of gene expression related with programmed cell death (PCD). In this article, the recent available information on W toxicity in plants and plant cells is reviewed, and the knowledge gaps and the most pertinent research directions are outlined. PMID:27137642

  13. Cardiac toxicities of antibiotics.

    PubMed Central

    Adams, H R; Parker, J L; Durrett, L R

    1978-01-01

    Isolated heart muscle preparations are useful in the study of cardiac toxicities of drugs and environmental chemicals: such tissues allow assessment of chemical effects on heart muscle that is free from indirect in vivo influences that can mask or even accentuate cardiac responses measured in the intact animal. In the present study, left atria of guinea pigs were used to demonstrate a direct cardiac depressant effect of greater-than-therapeutic concentrations of several aminoglycoside antibiotics. The toxic effect of these antibiotics seems to be a calcium-dependent event, and may prove useful to characterize contractile responses of the heart. Other antibiotic agents can also depress cardiovascular function, as summarized in this report, but mechanisms of action have not been clearly defined. PMID:720315

  14. Blindness from quinine toxicity.

    PubMed Central

    Bacon, P; Spalton, D J; Smith, S E

    1988-01-01

    We report a case of quinine overdose in a 47-year-old man who presented with blindness. Fundus photography demonstrates the acute and subsequent retinal changes, and his visual recovery to normal acuity with visual field constriction is documented. Pupillary and electrodiagnostic findings are recorded. Stellate ganglion block has been widely advocated as a helpful therapeutic measure, but out patient was treated with a unilateral stellate ganglion block without apparent benefit to that eye. From a review of the literature we believe that quinine produces its effects by toxicity on the retina rather than by vasoconstriction and that stellate ganglion block probably does not alter the natural history of the retinal toxicity. Images PMID:3281709

  15. Toxic compensation bills.

    PubMed Central

    Anderson, R C

    1985-01-01

    Congress has demonstrated interest in toxic compensation legislation, but not enough agreement to make significant progress. Advocates of reform claim that the legal system is heavily weighed against victims who seek compensation through the courts. Proposed reforms include a compensation fund and a cause of action in federal court. Critics have questioned whether these changes in the law would represent an improvement. Existing income replacement, medical cost reimbursement, and survivor insurance programs largely cover the losses of individuals with chronic disease. Thus, the need for an additional compensation is not clear. Furthermore, experience with compensation funds such as the Black Lung Fund suggests that political rather than scientific criteria may be used to determine eligibility. Finally, under the proposed financing mechanisms the compensation funds that are being debated would not increase incentives for care in the handling of hazardous wastes or toxic substances. PMID:4085440

  16. ACUTE TOXICITY OF NITRITE TO RAINBOW TROUT (SALMO GAIRDNERI): EFFECTS OF PH, NITRITE SPECIES, AND ANION SPECIES

    EPA Science Inventory

    The toxicity of nitrite to rainbow trout is pH-dependent within the range considered acceptable to most freshwater aquatic life (pH 6.5-9.0). Both of the nitrite species, NO2(-) and HNO2, are toxic. It is recommended that nitrite criteria to protect freshwater aquatic life be bas...

  17. MPI Profiling

    SciTech Connect

    Han, D K; Jones, T R

    2005-02-11

    The Message Passing Interface (MPI) is the de facto message-passing standard for massively parallel programs. It is often the case that application performance is a crucial factor, especially for solving grand challenge problems. While there have been many studies on the scalability of applications, there have not been many focusing on the specific types of MPI calls being made and their impact on application performance. Using a profiling tool called mpiP, a large spectrum of parallel scientific applications were surveyed and their performance results analyzed.

  18. Toxic Substances Control Act

    SciTech Connect

    Not Available

    1992-05-15

    This Reference Book contains a current copy of the Toxic Substances Control Act and those regulations that implement the statute and appear to be most relevant to DOE activities. The document is provided to DOE and contractor staff for informational purposes only and should not be interpreted as legal guidance. Questions concerning this Reference Book may be directed to Mark Petts, EH-231 (202/586-2609).

  19. Separations chemistry of toxic metals

    SciTech Connect

    Smith, P.; Barr, M.; Barrans, R.

    1996-04-01

    Sequestering and removing toxic metal ions from their surroundings is an increasingly active area of research and is gaining importance in light of current environmental contamination problems both within the DOE complex and externally. One method of separating metal ions is to complex them to a molecule (a ligand or chelator) which exhibits specific binding affinity for a toxic metal, even in the presence of other more benign metals. This approach makes use of the sometimes subtle differences between toxic and non-toxic metals resulting from variations in size, charge and shape. For example, toxic metals such as chromium, arsenic, and technetium exist in the environment as oxyanions, negatively charged species with a characteristic tetrahedral shape. Other toxic metals such as actinides and heavy metals are positively charged spheres with specific affinities for particular donor atoms such as oxygen (for actinides) and nitrogen (for heavy metals). In most cases the toxic metals are found in the presence of much larger quantities of less toxic metals such as sodium, calcium and iron. The selectivity of the chelators is critical to the goal of removing the toxic metals from their less toxic counterparts. The approach was to build a ligand framework that complements the unique characteristics of the toxic metal (size, charge and shape) while minimizing interactions with non-toxic metals. The authors have designed ligands exhibiting specificity for the target metals; they have synthesized, characterized and tested these ligands; and they have shown that they exhibit the proposed selectivity and cooperative binding effects.

  20. TOXICITY SCREENING WITH ZEBRAFISH ASSAY

    EPA Science Inventory

    The proposed toxicity screening will help EPA to prioritize chemicals for further testing, and it may also alert chemical manufacturers that some of their commercial products may be toxic. The proposed toxicity pathway studies will improve the research community’s abi...

  1. Keeping tabs on toxics.

    PubMed

    Young, J E

    1992-01-01

    The Toxic Release Inventory (TRI) is a list of all chemicals released by over 22,000 manufacturing sites across the US. The TRI was established by the Emergency Planning and Community Right to Know Act of 1986. The TRI is managed by the Environmental Protection Agency. It was opposed by the Reagan administration and many industry groups because it was seen as an increase in government paper work and regulation. It has turned out to be an easy-to-manage stimulate to change. Industry leaders have even proclaimed its ability to help raise awareness of pollution in the industry. The TRI is accessible through computers with modems on the TOXNET system at the National Library of Medicine in Bethesda for about 25$-35$/hour. It is also available through RTK NET which is operated jointly by OMB Watch and the Unison Institute. TRI is by no means complete. It covers an estimated 5% of the total toxic release in the US. It monitors the release of only 330 toxic chemicals leaving about 500 more out. It does not count releases from sites that process less then 25,000 pounds or that use less than 10,000 pounds of a listed chemical. It also only monitors steel, paper, chemical, petroleum refining activities. It does not monitor the releases from other manufacturing like oil and gas extraction, warehousing, transportation, hazardous waste disposal, incineration, and mining. PMID:12317431

  2. Dioxins and human toxicity.

    PubMed

    Marinković, Natalija; Pašalić, Daria; Ferenčak, Goran; Gršković, Branka; Stavljenić Rukavina, Ana

    2010-12-01

    The term dioxins usually refers to polychlorinated dibenzo-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). As 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) has the highest toxic potential, the toxic potentials of other PCDDs and PCDFs are defined in comparison with it. Human exposure to dioxins can be environmental (background), occupational, or accidental pollution. In the human body, dioxins are in part metabolised and eliminated, and the rest is stored in body fat. People vary in their capacity to eliminate TCDD, but it is also dose-dependent; the elimination rate is much faster at higher than lower levels. The liver microsomal P4501A1 enzyme oxygenates lipophilic chemicals such as dioxins. It is encoded by the CYP1A1 gene. Cytosolic aryl hydrocarbon receptor (AhR) mediates their carcinogenic action. It binds to dioxin, translocates to nucleus and together with hydrocarbon nuclear translocator (ARNT) and xenobiotic responsive element (XRE) increases the expression of CYP1A1.Dioxins are classified as known human carcinogens, but they also cause noncancerous effects like atherosclerosis, hypertension, and diabetes. Long-term exposures to dioxins cause disruption of the nervous, immune, reproductive, and endocrine system. Short-term exposure to high levels impairs the liver function and causes chloracne. The most sensitive population to dioxin exposure are the foetuses and infants.A large number of health effects have been documented in the scientific literature, and they all place dioxins among the most toxic chemicals known to man. PMID:21183436

  3. Toxicity of hexamethylenediamine.

    PubMed

    Kennedy, Gerald L

    2005-01-01

    Hexamethylendiamine (HMDA; CAS No. 124-09-4; 6055-52-3 for the dihydrochloride salt) is moderately toxic following acute doses/exposures with oral lethal doses in rats ranging from 750 to 1500 mg/kg. HMDA is extremely irritating to the skin and eyes and is not a sensitizer in guinea pigs. Repeated exposure inhalation studies have defined the upper respiratory tract to be the first target of HMDA. The irritation seen is proportional to the exposure concentration. Systemic damage is limited. Genetic testing is not extensive, but there is no indication of activity. HMDA is neither a developmental nor a reproductive toxin, but in one developmental study, the fetal No-observed-adverse-effect-level (NOAEL) was lower than that of the maternal animal. No carcinogenicity studies have been conducted. Documented human experience is limited, but indications of HMDA's irritative properties are found in the literature. HMDA does not persist or bioaccumulate in the environment. The chemical is not particularly toxic to fish and aquatic invertebrates but is quite toxic to algae. HMDA is rapidly absorbed and metabolized by the rat with little tissue storage. PMID:15720033

  4. 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

  5. The toxicity of methanol

    SciTech Connect

    Tephly, T.R. )

    1991-01-01

    Methanol toxicity in humans and monkeys is characterized by a latent period of many hours followed by a metabolic acidosis and ocular toxicity. This is not observed in most lower animals. The metabolic acidosis and blindness is apparently due to formic acid accumulation in humans and monkeys, a feature not seen in lower animals. The accumulation of formate is due to a deficiency in formate metabolism which is, in turn, related, in part, to low hepatic tetrahydrofolate (H{sub 4}folate). An excellent correlation between hepatic H{sub 4} folate and formate oxidation rates has been shown within and across species. Thus, humans and monkeys possess low hepatic H{sub 4}folate levels, low rates of formate oxidation and accumulation of formate after methanol. Formate, itself, produces blindness in monkeys in the absence of metabolic acidosis. In addition to low hepatic H{sub 4}folate concentrations, monkeys and humans also have low hepatic 10-formyl H{sub 4}folate dehydrogenase levels, the enzyme which is the ultimate catalyst for conversion of formate to carbon dioxide. This review presents the basis for the role of folic acid-dependent reactions in the regulation of methanol toxicity.

  6. Developing a Great Lakes air toxic emission inventory for Ontario

    SciTech Connect

    Wong, P.; Wong, S.; Bobet, E.; Wong, S.; Doan, C.

    1997-12-31

    In meeting the increasing needs for an emission inventory of toxic air pollutants around the Ontario portion of the Great Lakes Region, this pilot study was the first phase of the development of a comprehensive toxic air pollutant emission inventory system which will meet the demand from the Ontario domestic and international environmental management programs. In the ongoing development of a toxic air pollutant emission inventory for Ontario, source-release information gaps and emission estimation methodology deficiencies have been identified for future improvement. The state-of-the-art Regional Air Pollutant Inventory Development System (RAPIDS), being developed by the eight Great Lakes states and under the project management of the Great Lakes Commission, was used in this study to compile the emission inventories of selected toxic air pollutants from point, area and mobile sources for 1990. Other emission inventory related models/tools used in this study included the MOBILE 5C (modified version of US MOBILE 5a by Environment Canada), PART5 and other Environment Canada or Ontario specific emission profiles. An emission inventory of toxic air pollutants from the Great Lakes Commission`s 49 targeted compounds and the Canada-Ontario Agreement Respecting the Great Lakes Basin Ecosystem (COA) was developed in this study. This study identified major point source and area source categories that contributed significant emissions of the specified toxic air pollutants. This study demonstrated that RAPIDS can be used as a framework for the development of an Ontario toxic air pollutant emission inventory. However, further refinement of the RAPIDS system, the emission factors, and source specific toxic air speciation profiles would be required.

  7. HIV vaccine acceptability among immigrant Thai residents in Los Angeles: a mixed-method approach.

    PubMed

    Lee, Sung-Jae; Brooks, Ronald A; Newman, Peter A; Seiden, Danielle; Sangthong, Rassamee; Duan, Naihua

    2008-11-01

    This study examined HIV vaccine acceptability among immigrant Thai residents in Los Angeles, California. We combined a qualitative research method (focus groups) with an innovative market research method (conjoint analysis). Focus groups explored social issues, concerns, barriers and motivators associated with HIV vaccine acceptability. Conjoint analysis was used to assess preferences among eight hypothetical HIV vaccines with varying attribute profiles and the impact of various attributes on acceptability. Five main themes were identified in the focus groups regarding acceptance and utilization of preventive HIV vaccines: (1) vaccine characteristics, such as efficacy, physical side-effects and cost, (2) fear of a vaccine, (3) vaccine acceptability and optimism, (4) social and family responses and (5) behavioral disinhibition. Conjoint analysis revealed HIV vaccine acceptability ranging from 7.4 (SD = 19.4) to 85.2 (SD = 24.3) across eight hypothetical vaccines. The vaccine with the highest acceptability had the following attributes: 99% efficacy, no side-effects, 10 years of protection, protects against one sub-type, free, one dose and given by injection. Vaccine efficacy had the greatest impact on acceptability (51.4, p=.005), followed by side-effects (11.1, p=.005) and duration of protection (8.3, p=.005). Despite some apprehensions and concerns, Thai residents perceived an HIV vaccine as making an important contribution to society and to protecting oneself and one's family from HIV infection. Nevertheless, acceptability of a partially efficacious vaccine may be low, suggesting the need for tailored social marketing interventions that might emphasize a collectivistic rather than an individualistic focus. Assessing HIV vaccine acceptability using a mixed-method approach is feasible with Thai residents and should lend itself to HIV vaccine research with other Asian Pacific Islander populations in the US. PMID:18608068

  8. FINAL DISPOSAL OF RADIOACTIVE WASTE IN GERMANY: PLAN APPROVAL PROCESS OF KONRAD MINE AND ACCEPTANCE REQUIREMENTS

    SciTech Connect

    Bandt, Gabriele; Posnatzki, Britta; Beckers, Klaus-Arno

    2003-02-27

    Currently no final repository for any type of radioactive waste is operated in Germany. Preliminary Final Storage Acceptance Requirements for radioactive waste packages were published in 1995. Up to now these are the basis for treatment of radioactive waste in Germany. After licensing of the final repository these preliminary waste acceptance requirements are completed with licensing conditions. Some of these conditions affect the preliminary waste acceptance requirements, e. g. behavior of chemo-toxic substances in case of accidents in the final repository or the allowed maximum concentration of fissile material. The presented examples of radioactive waste conditioning campaigns demonstrate that no difficulties are expected in management, characterization and quality assurance of radioactive wastes due to the licensing conditions.

  9. Modern toxic antipersonnel projectiles.

    PubMed

    Gaillard, Yvan; Regenstreif, Philippe; Fanton, Laurent

    2014-12-01

    In the spring of 1944, Kurt von Gottberg, the SS police chief in Minsk, was shot and injured by 2 Soviet agents. Although he was only slightly injured, he died 6 hours later. The bullets were hollow and contained a crystalline white powder. They were 4-g bullets, semi-jacketed in cupronickel, containing 28 mg of aconitine. They were later known as akonitinnitratgeschosse. The Sipo (the Nazi security police) then ordered a trial with a 9-mm Parabellum cartridge containing Ditran, an anticholinergic drug with hallucinogenic properties causing intense mental confusion. In later years, QNB was used and given the NATO code BZ (3-quinuclidinyl-benzylate). It was proven that Saddam Hussein had this weapon (agent 15) manufactured and used it against the Kurds. Serbian forces used the same type of weapon in the Bosnian conflict, particularly in Srebrenica.The authors go on to list the Cold War toxic weapons developed by the KGB and the Warsaw pact countries for the discreet elimination of dissidents and proindependence leaders who had taken refuge in the West. These weapons include PSZh-13 launchers, the Troika electronic sequential pistol, and the ingenious 4-S110T captive piston system designed by the engineer Stechkin. Disguised as a cigarette case, it could fire a silent charge of potassium cyanide. This rogues gallery also includes the umbrella rigged to inject a pellet of ricin (or another phytalbumin of similar toxicity, such as abrin or crotin) that was used to assassinate the Bulgarian writer and journalist Georgi Markov on September 7, 1978, in London.During the autopsy, the discovery of a bullet burst into 4 or 5 parts has to make at once suspecting the use of a toxic substance. Toxicological analysis has to look for first and foremost aconitine, cyanide, suxamethonium, Ditran, BZ, or one of the toxic phytalbumins. The use of such complex weapons has to make suspect a powerful organization: army, secret service, terrorism. The existence of the Russian UDAR spray

  10. Role of retinal metabolism in methanol-induced retinal toxicity

    SciTech Connect

    Garner, C.D. |; Lee, E.W.; Terzo, T.S.; Louis-Ferdinand, R.T.

    1995-08-01

    Methanol is a toxicant that causes systemic and ocular toxicity after acute exposure. The folate-reduced (FR) rat is an excellent animal model that mimics characteristic human methanol toxic responses. The present study examines the role of the methanol metabolites formaldehyde and formate in the initiation of methanol-induced retinal toxicity. After a single oral dose of 3.0 g/kg methanol, blood methanol concentrations were not significantly different in FR rats compared with folate-sufficient (FS) (control) rats. However, FR rats treated with 3.0 g/kg methanol displayed elevated blood (14.6 mM) and vitreous humor (19.5 mM) formate levels and abnormal electroretinograms (loss of b-wave) 48 h postdose. FR rats pretreated with disulfiram (DSF) prior to 3.0 g/kg methanol treatment failed to display these symptoms. Formaldehyde was not detected in blood or vitreous humor with or without DSF treatment, suggesting that formate is the toxic metabolite in methanol-induced retinal toxicity. Additionally, creating a blood formate profile (14.2 mM at 48 h) similar to that observed in methanol-treated rats by iv infusion of pH-buffered formate does not alter the electroretinogram as is observed with methanol treatment. These data suggest that intraretinal metabolism of methanol is necessary for the formate-mediated initiation of methanol-induced retinal toxicity. 31 refs., 5 figs., 2 tabs.

  11. A novel titrimetric method for monitoring toxicity on nitrifying biofilms.

    PubMed

    Artiga, P; Oyanedel, V; Garrido, J M; Mendez, R

    2003-01-01

    A titrimetric method for monitoring toxicity in suspended biomass was applied in order to measure the activity of nitrifying biofilms and to determine the effect of several toxic compounds on the biofilm. Three typical tannery compounds, quebracho extract, NaCl and Cr+3 were selected to study their toxicity on the biofilms. The results obtained showed an acceptable repeatability of the method for all the toxicants tested with an average standard deviation of less than 10%. Biofilm systems showed higher resistance to the toxicants, when the results obtained using suspended nitrifying biomass, were compared with those found in the literature. The IC50 obtained with quebracho was 8.8 g/L of quebracho extract, while around 65% of maximum activity was attained with 8.7 g/L of NaCl or 120 mg/L Cr+3. The quebracho extract, NaCl and Cr+3 were 26%, 38% and 18%, respectively, less toxic in the biofilm system than for a suspended biomass culture. PMID:12701930

  12. Health and environmental-effects profile for nitroanilines

    SciTech Connect

    Not Available

    1985-03-01

    The Health and Environmental Effects Profile for nitroanilines was prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained from Agency program office files were evaluated as they pertained to potential human health, aquatic life, and environmental effects of hazardous-waste constituents. Quantitative estimates are presented, provided sufficient data are available. Existing data are insufficient to determine an Acceptable Daily Intake (ADI) or a carcinogenic potency factor for nitroanilines. The Reportable Quantity (RQ) value of 1, 10, 100, 1000, or 5000 pounds is used to determine the quantity of a hazardous substance for which notification is required in the event of a release as specified by CERCLA based on chronic toxicity. The RQ value for nitroanilines is 100.

  13. Health and environmental-effects profile for vanadium pentoxide

    SciTech Connect

    Not Available

    1985-04-01

    The Health and Environmental Effects Profile for vanadium pentoxide was prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained from Agency program office files were evaluated as they pertained to potential human health, aquatic life, and environmental effects of hazardous-waste constituents. Quantitative estimates are presented, provided sufficient data are available. Existing data are insufficient to determine an Acceptable Daily Intake (ADI) or a carcinogenic potency factor for vanadium pentoxide. The Reportable Quantity (RQ) value of 1, 10, 100, 1000, or 5000 pounds is used to determine the quantity of a hazardous substance for which notification is required in the event of a release as specified by CERCLA based on chronic toxicity. The RQ value for vanadium pentoxide is 100.

  14. Health and environmental-effects profile for nitromethane

    SciTech Connect

    Not Available

    1985-03-01

    The Health and Environmental Effects Profile for nitromethane was prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained from Agency program office files were evaluated as they pertained to potential human health, aquatic life, and environmental effects of hazardous-waste constituents. Quantitative estimates are presented, provided sufficient data are available. Existing data are insufficient to determine an Acceptable Daily Intake (ADI) or a carcinogenic potency factor for nitromethane. The Reportable Quantity (RQ) value of 1, 10, 100, 1000, or 5000 pounds is used to determine the quantity of a hazardous substance for which notification is required in the event of a release as specified by CERCLA based on chronic toxicity. The RQ value for nitromethane is 1000.

  15. Persistence of fermentative process to phenolic toxicity in groundwater

    SciTech Connect

    Wu, Y.X.; Lerner, D.N.; Banwart, S.A.; Thornton, S.E.; Pickup, R.W.

    2006-11-15

    The fermentation process is an important component in the biodegradation of organic compounds in natural and contaminated systems. Comparing with terminal electron-accepting processes (TEAPs), however, research on fermentation processes has to some extent been ignored in the past decades, particularly on the persistence of fermentation process in the presence of toxic organic pollutants. Both field and laboratory studies, presented here, showed that microbial processes in a groundwater-based system exhibited a differential inhibitory response to toxicity of phenolic compounds from coal tar distillation, thus resulting in the accumulation of volatile fatty acids (VFAs) and hydrogen. This indicated that fermentation processes could be more resistant to phenol toxicity than the subsequent TEAPs such as methanogenesis and sulfate reduction, thus providing us with more options for enhancing bioremediation processes.

  16. Children acceptance of laser dental treatment

    NASA Astrophysics Data System (ADS)

    Lazea, Andreea; Todea, Carmen

    2016-03-01

    Objectives: To evaluate the dental anxiety level and the degree of acceptance of laser assisted pedodontic treatments from the children part. Also, we want to underline the advantages of laser use in pediatric dentistry, to make this technology widely used in treating dental problems of our children patients. Methods: Thirty pediatric dental patients presented in the Department of Pedodontics, University of Medicine and Pharmacy "Victor Babeş", Timişoara were evaluated using the Wong-Baker pain rating scale, wich was administered postoperatory to all patients, to assess their level of laser therapy acceptance. Results: Wong-Baker faces pain rating scale (WBFPS) has good validity and high specificity; generally it's easy for children to use, easy to compare and has good feasibility. Laser treatment has been accepted and tolerated by pediatric patients for its ability to reduce or eliminate pain. Around 70% of the total sample showed an excellent acceptance of laser dental treatment. Conclusions: Laser technology is useful and effective in many clinical situations encountered in pediatric dentistry and a good level of pacient acceptance is reported during all laser procedures on hard and soft tissues.

  17. Physiologic correlates to background noise acceptance

    NASA Astrophysics Data System (ADS)

    Tampas, Joanna; Harkrider, Ashley; Nabelek, Anna

    2001-05-01

    Acceptance of background noise can be evaluated by having listeners indicate the highest background noise level (BNL) they are willing to accept while following the words of a story presented at their most comfortable listening level (MCL). The difference between the selected MCL and BNL is termed the acceptable noise level (ANL). One of the consistent findings in previous studies of ANL is large intersubject variability in acceptance of background noise. This variability is not related to age, gender, hearing sensitivity, personality, type of background noise, or speech perception in noise performance. The purpose of the current experiment was to determine if individual differences in physiological activity measured from the peripheral and central auditory systems of young female adults with normal hearing can account for the variability observed in ANL. Correlations between ANL and various physiological responses, including spontaneous, click-evoked, and distortion-product otoacoustic emissions, auditory brainstem and middle latency evoked potentials, and electroencephalography will be presented. Results may increase understanding of the regions of the auditory system that contribute to individual noise acceptance.

  18. A systematic evaluation of the safety and toxicity of fingolimod for its potential use in the treatment of acute myeloid leukaemia.

    PubMed

    Enjeti, Anoop K; D'Crus, Angel; Melville, Kathleen; Verrills, Nicole M; Rowlings, Philip

    2016-07-01

    Treatment of acute myeloid leukaemia (AML) is challenging and emerging treatment options include protein phosphatase 2A (PP2A) activators. Fingolimod is a known PP2A activator that inhibits multiple signalling pathways and has been used extensively in patients with multiple sclerosis and other indications. The initial positive results of PP2A activators in vitro and mouse models of AML are promising; however, its safety for use in AML has not been assessed. From human studies of fingolimod in other indications, it is possible to evaluate whether the safety and toxicity profile of the PP2A activators will allow their use in treating AML. A literature review was carried out to assess safety before the commencement of Phase I trials of the PP2A activator Fingolimod in AML. From human studies of fingolimod in other indications, it is possible to evaluate whether the safety and toxicity profile of the PP2A activators will allow their use in treating AML. A systematic review of published literature in Medline, EMBASE and the Cochrane Library of critical reviews was carried out. International standards for the design and reporting of search strategies were followed. Search terms and medical subject headings used in trials involving PP2A activators as well as a specific search were performed for 'adverse events', 'serious adverse events', 'delays in treatment', ' side effects' and 'toxicity' for primary objectives. Database searches were limited to papers published in the last 12 years and available in English. The search yielded 677 articles. A total of 69 journal articles were identified as relevant and included 30 clinical trials, 24 review articles and 15 case reports. The most frequently reported adverse events were nausea, diarrhoea, fatigue, back pain, influenza viral infections, nasopharyngitis and bronchitis. Specific safety concerns include monitoring of the heart rate and conduction at commencement of treatment as cardiotoxicity has been reported. There is

  19. 48 CFR 1346.503 - Place of acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Place of acceptance. 1346... QUALITY ASSURANCE Acceptance 1346.503 Place of acceptance. Insert a clause substantially similar to 1352.246-70, Place of Acceptance, in contracts and solicitations to indicate where the acceptance...

  20. 48 CFR 46.502 - Responsibility for acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... acceptance. 46.502 Section 46.502 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Acceptance 46.502 Responsibility for acceptance. Acceptance of... to a cognizant contract administration office or to another agency (see 42.202(g)), acceptance...

  1. 5 CFR 2601.204 - Conditions for acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Conditions for acceptance. 2601.204... IMPLEMENTATION OF OFFICE OF GOVERNMENT ETHICS STATUTORY GIFT ACCEPTANCE AUTHORITY Guidelines for Solicitation and Acceptance of Gifts § 2601.204 Conditions for acceptance. (a) No gift may be accepted that: (1)...

  2. 48 CFR 570.111 - Inspection and acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Inspection and acceptance... CONTRACTING PROGRAMS ACQUIRING LEASEHOLD INTERESTS IN REAL PROPERTY General 570.111 Inspection and acceptance... acceptance document must contain the square footage accepted and the acceptance date. Include the...

  3. 5 CFR 2601.204 - Conditions for acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Conditions for acceptance. 2601.204... IMPLEMENTATION OF OFFICE OF GOVERNMENT ETHICS STATUTORY GIFT ACCEPTANCE AUTHORITY Guidelines for Solicitation and Acceptance of Gifts § 2601.204 Conditions for acceptance. (a) No gift may be accepted that: (1)...

  4. 48 CFR 46.502 - Responsibility for acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... acceptance. 46.502 Section 46.502 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Acceptance 46.502 Responsibility for acceptance. Acceptance of... to a cognizant contract administration office or to another agency (see 42.202(g)), acceptance...

  5. How much do PCB toxic equivalents account for PHAH toxicity in predatory birds?

    PubMed

    Pereira, M Glória; Murk, A J; Van den Berg, H; Walker, Lee A; Shore, Richard F

    2014-10-01

    Various diffuse polyhalogenated aromatic hydrocarbons (PHAHs) exert common toxicity through the aryl hydrocarbon receptor (AhR). Apex predators spatially and temporally integrate diffuse contamination and simultaneous exposure can cause additive toxicity. We investigated the extent to which PCBs, still amongst the most prevalent PHAHs accumulated by predators, accounted for total PHAH toxicity in raptors and fish eating birds from Britain. We analysed egg or liver extracts from six species and compared chemically determined ΣPCB-TEQs concentrations with total AhR-mediated toxicity determined using the chemical-activated luciferase gene expression bioassay (CALUX-TEQ). Dioxin-like PCB profiles in eggs and livers were dominated by congeners 118, 105 and 167. ΣPCB-TEQ and CALUX-TEQ concentrations were positively associated but not in a 1:1 relationship. ΣPCB-TEQ were broadly similar to CALUX-TEQ concentrations in eggs and livers with CALUX-TEQ concentrations >50-80 and 160-320 pg g(-1) lipid respectively, but were lower than CALUX-TEQ concentrations in less contaminated samples. PMID:25062280

  6. [Acute toxic pneumopathies].

    PubMed

    Garnier, R

    1998-06-15

    The nature and extent of the acute injury due to toxic inhalants depend on the inhalant's solubility in water pH and chemical reactivity, on the aerodynamic diameter of particles (when the inhalant is an aerosol), and on the degree of exposure. Initial signs and symptoms indicate upper airways and bronchial irritation. Laryngeal oedema and (or) severe bronchospasm may be rapidly lethal. After cessation of exposure a transient improvement is generally observed; however a delayed pulmonary oedema may occur within the first 48 hours. On the following days, bacterial surinfection is a common complication. Possible long-term sequelae are reactive airways dysfunction syndrome and bronchiolitis obliterans. PMID:9781191

  7. Herbal toxicity in Zimbabwe.

    PubMed

    Nyazema, N Z

    1986-01-01

    Indigenous natural drugs are in common use in Zimbabwe because modern life-saving drugs are beyond the reach of nearly 85% of the population. These natural drugs have caused a number of poisoning cases. In a study of the records of four hospitals from 1971 to 1982, carried out to see how many people had been poisoned with herbal remedies, it was found that the number had increased since 1971. 50 traditional healers were questioned about record-keeping and knowledge of toxicity and Health Assistants were also interviewed. PMID:3798540

  8. Control of air toxics

    SciTech Connect

    Livengood, C.D.

    1995-03-01

    For more than 10 years, Argonne National Laboratory has supported the US DOE`s Flue Gas Cleanup Program objective by developing new or improved environmental controls for industries that use fossil fuels. Argonne`s pollutant emissions research has ranged from experiments in the basic chemistry of pollution-control systems, through laboratory-scale process development and testing, to pilot-scale field tests of several technologies. The work on air toxics is currently divided into two components: Investigating measures to improve the removal of mercury in existing pollution-control systems applied to coal combustion; and, Developing sensors and control techniques for emissions found in the textile industry.

  9. Nanoparticle toxicity and cancer

    NASA Astrophysics Data System (ADS)

    Prevenslik, T.

    2011-07-01

    Nanoparticles (NPs) have provided significant advancements in cancer treatment. But as in any technology, there is a darkside. Experiments have shown NPs in body fluids pose a health risk by causing DNA damage that in of itself may lead to cancer. To avoid the dilemma that NPs are toxic to both cancer cells and DNA alike, the mechanism of NP toxicity must be understood so that the safe use of NPs may go forward. Reactive oxidative species (ROS) of peroxide and hydroxyl radicals damage the DNA by chemical reaction, but require NPs provide energies of about 5 eV not possible by surface effects. Only electromagnetic (EM) radiations beyond ultraviolet (UV) levels may explain the toxicity of NPs. Indeed, experiments show DNA damage from <100 nm NPs mimic the same reaction pathways of conventional sources of ionizing radiation, Hence, it is reasonable to hypothesize that NPs produce their own source of UV radiation, albeit at low intensity. Ionizing radiation from NPs at UV levels is consistent with the theory of QED induced EM radiation. QED stands for quantum electrodynamics. By this theory, fine < 100 nm NPs absorb low frequency thermal energy in the far infrared (FIR) from collisions with the water molecules in body fluids. Since quantum mechanics (QM) precludes NPs from having specific heat, absorbed EM collision energy cannot be conserved by an increase in temperature. But total internal reflection (TIR) momentarily confines the absorbed EM energy within the NP. Conservation proceeds by the creation of QED photons by frequency up-conversion of the absorbed EM energy to the TIR confinement frequency, typically beyond the UV. Subsequently, the QED photons upon scattering from atoms within the NP avoid TIR confinement and leak UV to the surroundings, thereby explaining the remarkable toxicity of NPs. But QED radiation need not be limited to natural or man-made NPs. Extensions suggest UV radiation is produced from biological NPs within the body, e.g., enzyme induced

  10. [Toxic epidermal necrolysis].

    PubMed

    Carrillo-Esper, Raúl; Elizondo-Argueta, Sandra; Sánchez-Zúñiga, Martín de Jesús; Visoso-Palacios, Porfirio; Cedillo-Torres, Héctor; Carrillo-Córdova, Jorge Raúl

    2006-01-01

    Toxic epidermal necrolysis is the prototype of a proapoptotic disease characterized by system CD95 dysrregulation. Drugs constitute the main antigenic triggers. Hystopatologically it is characterized by epidermis detachment and necrosis with apoptotic keratinocytes. Clinical presentation includes erithematous-ampullous lesions in the skin and mucous membranes. It is associated with serious complications such as severe sepsis and septic shock. The management in the intensive care unit includes support treatment and specific treatment with immunoglobulins that alter disease course. Recombinant activated Factor VII is effective to control the associated microvascular haemorraghe. PMID:17022310

  11. Neurological oxygen toxicity.

    PubMed

    Farmery, Scott; Sykes, Oliver

    2012-10-01

    SCUBA diving has several risks associated with it from breathing air under pressure--nitrogen narcosis, barotrauma and decompression sickness (the bends). Trimix SCUBA diving involves regulating mixtures of nitrogen, oxygen and helium in an attempt to overcome the risks of narcosis and decompression sickness during deep dives, but introduces other potential hazards such as hypoxia and oxygen toxicity convulsions. This study reports on a seizure during the ascent phase, its potential causes and management and discusses the hazards posed to the diver and his rescuer by an emergency ascent to the surface. PMID:21900296

  12. Formulation approaches in mitigating toxicity of orally administrated drugs.

    PubMed

    Kadiyala, Irina; Tan, Elijah

    2013-01-01

    This paper provides an overview of current formulation approaches to mitigate toxicity of orally administrated drugs. The formulation approaches are characterized by their intended impact on a drug's pharmacokinetic parameters, pharmacological properties or metabolic pathways. Regulatory opportunities and constraints with focus on U.S. regulations in optimizing a drug's safety or efficacy profile are reviewed. The following formulation approaches are described: (i) pharmacokinetic-modulating and (ii) pharmacodynamic-modulating. In the pharmacokinetic-modulating approach, the pharmacokinetic profile of drug release is modified by, for example, a reduction in peak drug plasma concentration while preserving or improving AUC, thereby potentially reducing toxic effects that may be related to C(max). In the pharmacodynamic-modulating approach, the drug is co-dosed with pharmacologically active or nonpharmacologically active agent or agents intended for mitigation of the drug's toxicity. The pharmacodynamic-modulating approach requires information on the specificity of drug interactions with other compounds and also on metabolic pathways. Examples demonstrating successful formulation work in reducing drug toxicity are provided. The in-depth knowledge of the drug's PK and PD properties combined with a greater understanding of the biology of diseases are necessary for successful drug product formulation leading to optimized in vivo exposure and minimized toxicity. PMID:23317423

  13. [The acceptability of different oral contraceptive methods].

    PubMed

    Klinger, G; Fritzsche, H; Hempel, E; Carol, W; Böhme, W; Scholz, B; Grass, M; Chemnitius, K H

    1975-05-01

    Results of a survey of contraceptive acceptability are reported. In formation on oral and depot hormonal contraceptives was distributed to 1064 Ovosiston or Nonovlon users, 110 women using depot contraceptives, and 609 women who had never used hormonal contraception. The women's preferences with regard to administration schedule, and their perceptions of effectiveness and safety were noted. Non-users considered daily, weekly, or monthly administration acceptable, while only 2/3 of those taking oral contraceptives thought daily administration convenient. 90.2% of Deposiston patients did not care for daily administration. Deposiston patients also had the greatest confidence in their method. The authors believe on the basis of this survey that weekly administration may be highly acceptable alternative t o conventional oral contraception. PMID:1140078

  14. Conditions for the acceptance of deontic conditionals.

    PubMed

    Over, D E; Manktelow, K I; Hadjichristidis, C

    2004-06-01

    Recent psychological research has investigated how people assess the probability of an indicative conditional. Most people give the conditional probability of q given p as the probability of if p then q. Asking about the probability of an indicative conditional, one is in effect asking about its acceptability. But on what basis are deontic conditionals judged to be acceptable or unacceptable? Using a decision theoretic analysis, we argue that a deontic conditional, of the form if p then must q or if p then may q, will be judged acceptable to the extent that the p & q possibility is preferred to the p & not-q possibility. Two experiments are reported in which this prediction was upheld. There was also evidence that the pragmatic suitability of permission rules is partly determined by evaluations of the not-p & q possibility. Implications of these results for theories of deontic reasoning are discussed. PMID:15285599

  15. Acceptance Priority Ranking & Annual Capacity Report

    SciTech Connect

    2004-07-31

    The Nuclear Waste Policy Act of 1982, as amended (the Act), assigns the Federal Government the responsibility for the disposal of spent nuclear fuel and high-level waste. Section 302(a) of the Act authorizes the Secretary to enter into contracts with the owners and generators of commercial spent nuclear fuel and/or high-level waste. The Standard Contract for Disposal of Spent Nuclear Fuel and/or High-Level Radioactive Waste (Standard Contract) established the contractual mechanism for the Department's acceptance and disposal of spent nuclear fuel and high-level waste. It includes the requirements and operational responsibilities of the parties to the Standard Contract in the areas of administrative matters, fees, terms of payment, waste acceptance criteria, and waste acceptance procedures. The Standard Contract provides for the acquisition of title to the spent nuclear fuel and/or high-level waste by the Department, its transportation to Federal facilities, and its subsequent disposal.

  16. Long Trace Profiler survey results

    SciTech Connect

    Irick, Steve.

    1999-07-01

    Today the Long Trace Profiler (LTP) is widely accepted as a viable way to measure X-ray mirrors, and at some institutions is the only instrument available for measuring long, high-curvature aspheres. Although some questions of absolute accuracy over the entire LTP measurement range remain unanswered, a comparison of LTPs can still be made to assess measurement variation. Recently a round robin survey of some LTPs within the United States has been made using a single set of mirrors. These mirrors were used to characterize the performance of an LTP over its advertised range of operation. The results of this survey are presented here.

  17. Species-Specific Predictive Signatures of Developmental Toxicity Using the ToxCast Chemical Library

    EPA Science Inventory

    EPA’s ToxCastTM project is profiling the in vitro bioactivity of chemicals to generate predictive signatures that correlate with observed in vivo toxicity. In vitro profiling methods from ToxCast data consist of over 600 high-throughput screening (HTS) and high-content screening ...

  18. Species-specific predictive models of developmental toxicity using the ToxCast chemical library

    EPA Science Inventory

    EPA’s ToxCastTM project is profiling the in vitro bioactivity of chemicals to generate predictive models that correlate with observed in vivo toxicity. In vitro profiling methods are based on ToxCast data, consisting of over 600 high-throughput screening (HTS) and high-content sc...

  19. Efficacy and acceptability of perindopril in essential hypertension.

    PubMed

    Sukonthasarn, A; Ratanaprakarn, R; Koanantakul, B; Ngam-Ukos, P

    1994-06-01

    The clinical efficacy and acceptability of once-daily perindopril (4 to 8 mg) monotherapy and in combination with hydrochlorothiazide (50 mg/day) was studied in mild to moderate stable essential hypertensive patients in 4 centres in Thailand. After 2-4 weeks of placebo run-in period, patients received active treatment for 3 months starting with 4 mg perindopril once daily. Dose titration was at second and third month of active treatment if the supine DBP was > 90 mmHg. The dose was doubled and if necessary, 50 mg/day hydrochlorothiazide was added in the last month. The results in 95 patients showed that the mean reduction in supine SBP/DBP at 1, 2 and 3 months of treatment was 10.3/8.0, 13.2/8.7 and 19.1/13.7 mmHg respectively. At the end of the study, 80 per cent of the patients showed normalisation of the supine diastolic blood pressure (supine DBP < or = 90 mmHg) with 30 per cent receiving combined therapy of perindopril and hydrochlorothiazide. There was no significant change in routine haematology or serum biochemistry except for slight increase of potassium levels in patients receiving 8 mg perindopril monotherapy. The incidence of side effects and withdrawal from treatment were quite low. Cough was the major side effect reported comprising 13.6 per cent with only 1 case withdrawn. The study confirms the previous studies that perindopril had satisfactory antihypertensive efficacy and acceptability profiles. PMID:7869013

  20. Hanford Site solid waste acceptance criteria

    SciTech Connect

    Ellefson, M.D.

    1998-07-01

    Order 5820.2A requires that each treatment, storage, and/or disposal facility (referred to in this document as TSD unit) that manages low-level or transuranic waste (including mixed waste and TSCA PCB waste) maintain waste acceptance criteria. These criteria must address the various requirements to operate the TSD unit in compliance with applicable safety and environmental requirements. This document sets forth the baseline criteria for acceptance of radioactive waste at TSD units operated by WMH. The criteria for each TSD unit have been established to ensure that waste accepted can be managed in a manner that is within the operating requirements of the unit, including environmental regulations, DOE Orders, permits, technical safety requirements, waste analysis plans, performance assessments, and other applicable requirements. Acceptance criteria apply to the following TSD units: the Low-Level Burial Grounds (LLBG) including both the nonregulated portions of the LLBG and trenches 31 and 34 of the 218-W-5 Burial Ground for mixed waste disposal; Central Waste Complex (CWC); Waste Receiving and Processing Facility (WRAP); and T Plant Complex. Waste from all generators, both from the Hanford Site and from offsite facilities, must comply with these criteria. Exceptions can be granted as provided in Section 1.6. Specific waste streams could have additional requirements based on the 1901 identified TSD pathway. These requirements are communicated in the Waste Specification Records (WSRds). The Hanford Site manages nonradioactive waste through direct shipments to offsite contractors. The waste acceptance requirements of the offsite TSD facility must be met for these nonradioactive wastes. This document does not address the acceptance requirements of these offsite facilities.