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Sample records for highly toxic chemicals

  1. Phase out persistent, bioaccumulative or highly toxic chemicals.

    PubMed

    Easthope, Tracey; Valeriano, Laurie

    2007-01-01

    Chemicals such as lindane, lead compounds, and some brominated flame retardants and organophosphate pesticides are examples of persistent, bio-accumulative, and/or highly toxic chemicals that continue to be used in commerce, although strong evidence exists that they pose threats to human and ecosystem health. These and other chemicals, by virtue of their characteristics, are very difficult to manage without unacceptable threats to workers, the environment, or ecosystems. Chemicals that cannot be safely managed should be prioritized for phase out. A transparent process to further identify and prioritize the list of chemicals for phase out is needed. With few exceptions, the U.S. government lacks the authority or an efficient policy instrument to prevent these high-priority chemicals from being used in products and processes or released to the environment. It also has been very difficult for state and local governments to restrict these chemicals. Policy instruments to efficiently and effectively phase out problematic chemicals are needed at all levels of government.

  2. Integration of Dosimetry, Exposure and High-Throughput Screening Data in Chemical Toxicity Assessment

    EPA Science Inventory

    High-throughput in vitro toxicity screening can provide an efficient way to identify potential biological targets for chemicals. However, relying on nominal assay concentrations may misrepresent potential in vivo effects of these chemicals due to differences in bioavailability, c...

  3. Integration of Dosimetry, Exposure and High-Throughput Screening Data in Chemical Toxicity Assessment

    EPA Science Inventory

    High-throughput in vitro toxicity screening can provide an efficient way to identify potential biological targets for chemicals. However, relying on nominal assay concentrations may misrepresent potential in vivo effects of these chemicals due to differences in bioavailability, c...

  4. 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.

  5. 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

  6. Estimating Toxicity Pathway Activating Doses for High Throughput Chemical Risk Assessments

    EPA Science Inventory

    Estimating a Toxicity Pathway Activating Dose (TPAD) from in vitro assays as an analog to a reference dose (RfD) derived from in vivo toxicity tests would facilitate high throughput risk assessments of thousands of data-poor environmental chemicals. Estimating a TPAD requires def...

  7. Estimating Toxicity Pathway Activating Doses for High Throughput Chemical Risk Assessments

    EPA Science Inventory

    Estimating a Toxicity Pathway Activating Dose (TPAD) from in vitro assays as an analog to a reference dose (RfD) derived from in vivo toxicity tests would facilitate high throughput risk assessments of thousands of data-poor environmental chemicals. Estimating a TPAD requires def...

  8. Sources of toxicity and exposure information for identifying chemicals of high concern to children

    SciTech Connect

    Stone, Alex; Delistraty, Damon

    2010-11-15

    Due to the large number of chemicals in commerce without adequate toxicity characterization data, coupled with an ineffective federal policy for chemical management in the United States, many states are grappling with the challenge to identify toxic chemicals that may pose a risk to human health and the environment. Specific populations (e.g., children, elderly) are particularly sensitive to these toxic chemicals. In 2008, the Children's Safe Product Act (CSPA) was passed in Washington State. The CSPA included specific requirements to identify High Priority Chemicals (HPCs) and Chemicals of High Concern to Children (CHCCs). To implement this legislation, a methodology was developed to identify HPCs from authoritative scientific and regulatory sources on the basis of toxicity criteria. Another set of chemicals of concern was then identified from authoritative sources, based on their potential exposure to children. Exposure potential was evaluated by identifying chemicals detected in biomonitoring studies (i.e., human tissues), as well as those present in residential exposure media (e.g., indoor air, house dust, drinking water, consumer products). Accordingly, CHCCs were defined as HPCs that also appear in biomonitoring studies or relevant exposure media. For chemicals with unique Chemical Abstracts Service (CAS) numbers, we identified 2044 HPCs and 2219 chemicals with potential exposure to children, resulting in 476 CHCCs. The process of chemical identification is dynamic, so that chemicals may be added or subtracted as new information becomes available. Although beyond the scope of this paper, the 476 CHCCs will be prioritized in a more detailed assessment, based on the strength and weight of evidence of toxicity and exposure data. Our approach was developed to be flexible which allows the addition or removal of specific sources of toxicity or exposure information, as well as transparent to allow clear identification of inputs. Although the methodology was

  9. How Much is Too Much? Toxic Chemicals in High School Labs.

    ERIC Educational Resources Information Center

    Nagel, Miriam C.

    1982-01-01

    Lists 37 chemicals classified as suspected carcinogens and suspected teratogens (chemicals capable of producing malformations in an embryo). Offers suggestions to high school chemistry teachers for conducting safe laboratory investigations by avoiding use of these potentially toxic materials. (Author/JN)

  10. How Much is Too Much? Toxic Chemicals in High School Labs.

    ERIC Educational Resources Information Center

    Nagel, Miriam C.

    1982-01-01

    Lists 37 chemicals classified as suspected carcinogens and suspected teratogens (chemicals capable of producing malformations in an embryo). Offers suggestions to high school chemistry teachers for conducting safe laboratory investigations by avoiding use of these potentially toxic materials. (Author/JN)

  11. High Throughput Screening of Toxicity Pathways Perturbed by Environmental Chemicals

    EPA Science Inventory

    Toxicology, a field largely unchanged over the past several decades, is undergoing a significant transformation driven by a number of forces – the increasing number of chemicals needing assessment, changing legal requirements, advances in biology and computer science, and concern...

  12. High Throughput Screening of Toxicity Pathways Perturbed by Environmental Chemicals

    EPA Science Inventory

    Toxicology, a field largely unchanged over the past several decades, is undergoing a significant transformation driven by a number of forces – the increasing number of chemicals needing assessment, changing legal requirements, advances in biology and computer science, and concern...

  13. Estimating the impact of high-production-volume chemicals on remote ecosystems by toxic pressure calculation.

    PubMed

    Harbers, Jasper V; Huijbregts, Mark A J; Posthuma, Leo; Van de Meent, Dik

    2006-03-01

    Although many chemicals are in use, the environmental impacts of only a few have been established, usually on per-chemical basis. Uncertainty remains about the overall impact of chemicals. This paper estimates combined toxic pressure on coastal North Sea ecosystems from 343 high-production-volume chemicals used within the catchment of rivers Rhine, Meuse, and Scheldt. Multimedia fate modeling and species sensitivity distribution-based effects estimation are applied. Calculations start from production volumes and emission rates and use physicochemical substance properties and aquatic ecotoxicity data. Parameter uncertainty is addressed by Monte Carlo simulations. Results suggest that the procedure is technically feasible. Combined toxic pressure of all 343 chemicals in coastal North Seawater is 0.025 (2.5% of the species are exposed to concentration levels above EC50 values), with a wide confidence interval of nearly 0-1. This uncertainty appears to be largely due to uncertainties in interspecies variances of aquatic toxicities and, to a lesser extent, to uncertainties in emissions and degradation rates. Due to these uncertainties, the results support gross ranking of chemicals in categories: negligible and possibly relevant contributions only. With 95% confidence, 283 of the 343 chemicals (83%) contribute negligibly (less than 0.1%) to overall toxic pressure, and only 60 (17%) need further consideration.

  14. Quantitative high-throughput screening for chemical toxicity in a population-based in vitro model.

    PubMed

    Lock, Eric F; Abdo, Nour; Huang, Ruili; Xia, Menghang; Kosyk, Oksana; O'Shea, Shannon H; Zhou, Yi-Hui; Sedykh, Alexander; Tropsha, Alexander; Austin, Christopher P; Tice, Raymond R; Wright, Fred A; Rusyn, Ivan

    2012-04-01

    A shift in toxicity testing from in vivo to in vitro may efficiently prioritize compounds, reveal new mechanisms, and enable predictive modeling. Quantitative high-throughput screening (qHTS) is a major source of data for computational toxicology, and our goal in this study was to aid in the development of predictive in vitro models of chemical-induced toxicity, anchored on interindividual genetic variability. Eighty-one human lymphoblast cell lines from 27 Centre d'Etude du Polymorphisme Humain trios were exposed to 240 chemical substances (12 concentrations, 0.26nM-46.0μM) and evaluated for cytotoxicity and apoptosis. qHTS screening in the genetically defined population produced robust and reproducible results, which allowed for cross-compound, cross-assay, and cross-individual comparisons. Some compounds were cytotoxic to all cell types at similar concentrations, whereas others exhibited interindividual differences in cytotoxicity. Specifically, the qHTS in a population-based human in vitro model system has several unique aspects that are of utility for toxicity testing, chemical prioritization, and high-throughput risk assessment. First, standardized and high-quality concentration-response profiling, with reproducibility confirmed by comparison with previous experiments, enables prioritization of chemicals for variability in interindividual range in cytotoxicity. Second, genome-wide association analysis of cytotoxicity phenotypes allows exploration of the potential genetic determinants of interindividual variability in toxicity. Furthermore, highly significant associations identified through the analysis of population-level correlations between basal gene expression variability and chemical-induced toxicity suggest plausible mode of action hypotheses for follow-up analyses. We conclude that as the improved resolution of genetic profiling can now be matched with high-quality in vitro screening data, the evaluation of the toxicity pathways and the effects of

  15. 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...

  16. 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...

  17. Quantitative high content imaging of cellular adaptive stress response pathways in toxicity for chemical safety assessment.

    PubMed

    Wink, Steven; Hiemstra, Steven; Huppelschoten, Suzanna; Danen, Erik; Niemeijer, Marije; Hendriks, Giel; Vrieling, Harry; Herpers, Bram; van de Water, Bob

    2014-03-17

    Over the past decade, major leaps forward have been made on the mechanistic understanding and identification of adaptive stress response landscapes underlying toxic insult using transcriptomics approaches. However, for predictive purposes of adverse outcome several major limitations in these approaches exist. First, the limited number of samples that can be analyzed reduces the in depth analysis of concentration-time course relationships for toxic stress responses. Second these transcriptomics analysis have been based on the whole cell population, thereby inevitably preventing single cell analysis. Third, transcriptomics is based on the transcript level, totally ignoring (post)translational regulation. We believe these limitations are circumvented with the application of high content analysis of relevant toxicant-induced adaptive stress signaling pathways using bacterial artificial chromosome (BAC) green fluorescent protein (GFP) reporter cell-based assays. The goal is to establish a platform that incorporates all adaptive stress pathways that are relevant for toxicity, with a focus on drug-induced liver injury. In addition, cellular stress responses typically follow cell perturbations at the subcellular organelle level. Therefore, we complement our reporter line panel with reporters for specific organelle morphometry and function. Here, we review the approaches of high content imaging of cellular adaptive stress responses to chemicals and the application in the mechanistic understanding and prediction of chemical toxicity at a systems toxicology level.

  18. A high-throughput method for assessing chemical toxicity using a Caenorhabditis elegans reproduction assay

    SciTech Connect

    Boyd, Windy A.; McBride, Sandra J.; Rice, Julie R.; Snyder, Daniel W.; Freedman, Jonathan H.

    2010-06-01

    The National Research Council has outlined the need for non-mammalian toxicological models to test the potential health effects of a large number of chemicals while also reducing the use of traditional animal models. The nematode Caenorhabditis elegans is an attractive alternative model because of its well-characterized and evolutionarily conserved biology, low cost, and ability to be used in high-throughput screening. A high-throughput method is described for quantifying the reproductive capacity of C. elegans exposed to chemicals for 48 h from the last larval stage (L4) to adulthood using a COPAS Biosort. Initially, the effects of exposure conditions that could influence reproduction were defined. Concentrations of DMSO vehicle {<=} 1% did not affect reproduction. Previous studies indicated that C. elegans may be influenced by exposure to low pH conditions. At pHs greater than 4.5, C. elegans reproduction was not affected; however below this pH there was a significant decrease in the number of offspring. Cadmium chloride was chosen as a model toxicant to verify that automated measurements were comparable to those of traditional observational studies. EC{sub 50} values for cadmium for automated measurements (176-192 {mu}M) were comparable to those previously reported for a 72-h exposure using manual counting (151 {mu}M). The toxicity of seven test toxicants on C. elegans reproduction was highly correlative with rodent lethality suggesting that this assay may be useful in predicting the potential toxicity of chemicals in other organisms.

  19. A HIGH-THROUGHPUT METHOD FOR ASSESSING CHEMICAL TOXICITY USING A CAENORHABDITIS ELEGANS REPRODUCTION ASSAY

    PubMed Central

    Boyd, Windy A.; McBride, Sandra J.; Rice, Julie R.; Snyder, Daniel W.; Freedman, Jonathan H.

    2010-01-01

    The National Research Council has outlined the need for non-mammalian toxicological models to test the potential health effects of a large number of chemicals while also reducing the use of traditional animal models. The nematode Caenorhabditis elegans is an attractive alternative model because of its well-characterized and evolutionarily-conserved biology, low cost, and ability to be used in high-throughput screening. A high-throughput method is described for quantifying the reproductive capacity of C. elegans exposed to chemicals for 48 h from the last larval stage (L4) to adulthood using a COPAS Biosort. Initially, the effects of exposure conditions that could influence reproduction were defined. Concentrations of DMSO vehicle ≤ 1% did not affect reproduction. Previous studies indicated that C. elegans may be influenced by exposure to low pH conditions. At pHs greater than 4.5, C. elegans reproduction was not affected, however below this pH there was a significant decrease in the number of offspring. Cadmium chloride was chosen as a model toxicant to verify that automated measurements were comparable to those of traditional observational studies. EC50 values for cadmium for automated measurements (176-192 μM) were comparable to those previously reported for a 72-h exposure using manual counting (151 μM). The toxicity of seven test toxicants on C. elegans reproduction was highly correlative with rodent lethality suggesting that this assay may be useful in predicting the potential toxicity of chemicals in other organisms. PMID:20206647

  20. A systematic study of mitochondrial toxicity of environmental chemicals using quantitative high throughput screening

    PubMed Central

    Attene-Ramos, Matias S.; Huang, Ruili; Sakamuru, Srilatha; Witt, Kristine L.; Beeson, Gyda C.; Shou, Louie; Schnellmann, Rick G.; Beeson, Craig C.; Tice, Raymond R.; Austin, Christopher P.; Xia, Menghang

    2014-01-01

    A goal of the Tox21 program is to transit toxicity testing from traditional in vivo models to in vitro assays that assess how chemicals affect cellular responses and toxicity pathways. A critical contribution of the NIH Chemical Genomics center (NCGC) to the Tox21 program is the implementation of a quantitative high throughput screening (qHTS) approach, using cell- and biochemical-based assays to generate toxicological profiles for thousands of environmental compounds. Here, we evaluated the effect of chemical compounds on mitochondrial membrane potential in HepG2 cells by screening a library of 1,408 compounds provided by the National Toxicology Program (NTP) in a qHTS platform. Compounds were screened over 14 concentrations, and results showed that 91 and 88 compounds disrupted mitochondrial membrane potential after treatment for one or five h, respectively. Seventy-six compounds active at both time points were clustered by structural similarity, producing 11 clusters and 23 singletons. Thirty-eight compounds covering most of the active chemical space were more extensively evaluated. Thirty-six of the 38 compounds were confirmed to disrupt mitochondrial membrane potential using a fluorescence plate reader and 35 were confirmed using a high content imaging approach. Among the 38 compounds, 4 and 6 induced LDH release, a measure of cytotoxicity, at 1 or 5 h, respectively. Compounds were further assessed for mechanism of action (MOA) by measuring changes in oxygen consumption rate, which enabled identification of 20 compounds as uncouplers. This comprehensive approach allows for evaluation of thousands of environmental chemicals for mitochondrial toxicity and identification of possible MOAs. PMID:23895456

  1. An abbreviated repeat dose and reproductive/developmental toxicity test for high production volume chemicals.

    PubMed

    Scala, R A; Bevan, C; Beyer, B K

    1992-08-01

    A novel protocol is described for obtaining preliminary data on repeated dose systemic effects and reproductive/developmental toxicity. The test protocol was developed by a group of experts at the request of the U.S. Environmental Protection Agency (EPA) for use as part of a Screening Information Data Set on high production volume chemicals. Interest in this protocol is shared by several regulatory agencies, including the Organization for Economic Cooperation, the European Community, and the EPA. To validate the study protocol, ethylene glycol monomethyl ether (EGME) was used. After a dosing period of approximately 6 weeks, EGME showed both systemic and reproductive/developmental effects similar to those previously reported using standard protocols. Thus, this test protocol may be used as a screening tool for high production volume chemicals.

  2. Controlling toxic chemicals

    SciTech Connect

    Postel, S.

    1988-01-01

    The use of pesticides in agriculture and the disposal of industrial chemical wastes constitute two major pathways by which people are inadvertently exposed to toxics. These practices release hundreds of millions of tons of potentially hazardous substances into the environment each year. In many ways the situation with industrial chemical waste parallels the predicament with pesticides: Not only are current practices contaminating the environment and creating health risks, but they are unsustainable over the long term. Strategies that reduce pesticide use in agriculture and minimize waste generation in industry offer cost-effective approaches to decreasing risks from toxics. Such strategies differ fundamentally from current practice and require new ways of thinking. The quick fixes of pesticide spraying and end-of-pipe pollution control are replaced with new production systems aimed at reconciling economic profits with environmental protection. Current efforts in integrated pest management and industrial waste reduction, although clearly promising, only hint at their long-term potential for detoxifying the environment.

  3. Including Bioconcentration Kinetics for the Prioritization and Interpretation of Regulatory Aquatic Toxicity Tests of Highly Hydrophobic Chemicals.

    PubMed

    Kwon, Jung-Hwan; Lee, So-Young; Kang, Hyun-Joong; Mayer, Philipp; Escher, Beate I

    2016-11-01

    Worldwide, regulations of chemicals require short-term toxicity data for evaluating hazards and risks of the chemicals. Current data requirements on the registration of chemicals are primarily based on tonnage and do not yet consider properties of chemicals. For example, short-term ecotoxicity data are required for chemicals with production volume greater than 1 or 10 ton/y according to REACH, without considering chemical properties. Highly hydrophobic chemicals are characterized by low water solubility and slow bioconcentration kinetics, which may hamper the interpretation of short-term toxicity experiments. In this work, internal concentrations of highly hydrophobic chemicals were predicted for standard acute ecotoxicity tests at three trophic levels, algae, invertebrate, and fish. As demonstrated by comparison with maximum aqueous concentrations at water solubility, chemicals with an octanol-water partition coefficient (Kow) greater than 10(6) are not expected to reach sufficiently high internal concentrations for exerting effects within the test duration of acute tests with fish and invertebrates, even though they might be intrinsically toxic. This toxicity cutoff was explained by the slow uptake, i.e., by kinetics, not by thermodynamic limitations. Predictions were confirmed by data entries of the OECD's screening information data set (SIDS) (n = 746), apart from a few exceptions concerning mainly organometallic substances and those with inconsistency between water solubility and Kow. Taking error propagation and model assumptions into account, we thus propose a revision of data requirements for highly hydrophobic chemicals with log Kow > 7.4: Short-term toxicity tests can be limited to algae that generally have the highest uptake rate constants, whereas the primary focus of the assessment should be on persistence, bioaccumulation, and long-term effects.

  4. Evaluating the Toxicity Pathways Using High-Throughput Environmental Chemical Data

    EPA Science Inventory

    The application of HTS methods to the characterization of human phenotypic response to environmental chemicals is a largely unexplored area of pharmacogenomics. The U.S. Environmental Protection Agency (EPA), through its ToxCast program, is developing predictive toxicity approach...

  5. Evaluating the Toxicity Pathways Using High-Throughput Environmental Chemical Data

    EPA Science Inventory

    The application of HTS methods to the characterization of human phenotypic response to environmental chemicals is a largely unexplored area of pharmacogenomics. The U.S. Environmental Protection Agency (EPA), through its ToxCast program, is developing predictive toxicity approach...

  6. EXPANDING CHEMICAL-TOXICITY INFORMATION ...

    EPA Pesticide Factsheets

    We find that the connection between structure and biological response is not symmetric, with biological response better at predicting chemical structure than vice versa. *ToxCast Toxicity Reference Database. We find that the connection between structure and biological response is not symmetric, with biological response better at predicting chemical structure than vice versa. *ToxCast Toxicity Reference Database.

  7. Classification of Chemicals Based On Structured Toxicity ...

    EPA Pesticide Factsheets

    Thirty years and millions of dollars worth of pesticide registration toxicity studies, historically stored as hardcopy and scanned documents, have been digitized into highly standardized and structured toxicity data within the Toxicity Reference Database (ToxRefDB). Toxicity-based classifications of chemicals were performed as a model application of ToxRefDB. These endpoints will ultimately provide the anchoring toxicity information for the development of predictive models and biological signatures utilizing in vitro assay data. Utilizing query and structured data mining approaches, toxicity profiles were uniformly generated for greater than 300 chemicals. Based on observation rate, species concordance and regulatory relevance, individual and aggregated effects have been selected to classify the chemicals providing a set of predictable endpoints. ToxRefDB exhibits the utility of transforming unstructured toxicity data into structured data and, furthermore, into computable outputs, and serves as a model for applying such data to address modern toxicological problems.

  8. Toxicity identification and high-efficiency treatment of aging chemical industrial wastewater from the Hangu Reservoir, China.

    PubMed

    Li, Wei; Hua, Tao; Zhou, Qixing; Zhang, Shuguang; Rong, Weiying

    2011-01-01

    The Hangu Reservoir, located in Binhai New Area, Tianjin, China, receives mixed wastewater from a chemical industrial park. The aging chemical industrial wastewater is less biodegradable and contains complex hazardous substances, thus having an adverse effect on local ecological service function of the reservoir and on local economic and social development. In this study, key toxicants in the aging chemical industrial wastewater from the Hangu Reservoir were systematically identified by the toxicity identification evaluations (TIEs), and the treatment efficiency of the aging chemical industrial wastewater was examined and optimized by a municipal wastewater treatment process simulated in a laboratory. According to the TIE results using and wheat seeds as tested organisms, Cl, Cu, Pb, and Zn were identified as key toxicants in the aging chemical industrial wastewater, with concentrations of 7349.11, 0.01, 0.07, and 0.07 mg L, respectively, which were confirmed by subsequent spiking approaches. Based on the TIE results, the aging chemical industrial wastewater could be classified as high-salinity wastewater. The co-treatment of the aging chemical industrial wastewater and municipal wastewater may be an effective and low-cost method. The treatment efficiency of the mixed wastewater increased with an increase in the volume ratio of municipal wastewater to aging chemical industrial wastewater. When the volume ratio was 10:1, the best removal efficiencies of chemical oxygen demand, total N, and total P were up to 85.1, 89.3, and 96.5%, respectively, whereas the toxicity unit of the treated wastewater was reduced to 0.50.

  9. Hierarchical dose-response modeling for high-throughput toxicity screening of environmental chemicals.

    PubMed

    Wilson, Ander; Reif, David M; Reich, Brian J

    2014-03-01

    High-throughput screening (HTS) of environmental chemicals is used to identify chemicals with high potential for adverse human health and environmental effects from among the thousands of untested chemicals. Predicting physiologically relevant activity with HTS data requires estimating the response of a large number of chemicals across a battery of screening assays based on sparse dose-response data for each chemical-assay combination. Many standard dose-response methods are inadequate because they treat each curve separately and under-perform when there are as few as 6-10 observations per curve. We propose a semiparametric Bayesian model that borrows strength across chemicals and assays. Our method directly parametrizes the efficacy and potency of the chemicals as well as the probability of response. We use the ToxCast data from the U.S. Environmental Protection Agency (EPA) as motivation. We demonstrate that our hierarchical method provides more accurate estimates of the probability of response, efficacy, and potency than separate curve estimation in a simulation study. We use our semiparametric method to compare the efficacy of chemicals in the ToxCast data to well-characterized reference chemicals on estrogen receptor α (ERα) and peroxisome proliferator-activated receptor γ (PPARγ) assays, then estimate the probability that other chemicals are active at lower concentrations than the reference chemicals.

  10. Risk assessment of high-energy chemicals by in vitro toxicity screening and quantitative structure-activity relationships.

    PubMed

    Trohalaki, Steven; Zellmer, Robert J; Pachter, Ruth; Hussain, Saber M; Frazier, John M

    2002-08-01

    Hydrazine propellants pose a substantial operational concern to the U.S. Air Force and to the aerospace industry because of their toxicity. In our continuing efforts to develop methods for the prediction of the toxicological response to such materials, we have measured in vitro toxicity endpoints for a series of high-energy chemicals (HECs) that were recently proposed as propellants. The HECs considered are structurally diverse and can be classified into four chemical types (hydrazine-based, amino-based, triazoles, and a quaternary ammonium salt), although most are hydrazine derivatives. We measured the following endpoints in primary cultures of isolated rat hepatocytes: mitochondrial function (MTT), lactate dehydrogenase leakage (LDH), generation of reactive oxygen species (ROS), and total glutathione content (GSH). In several instances, effective concentrations (EC) were indeterminate, and only lower limits to the measured endpoints could be ascertained. Using molecular descriptors calculated with a semiempirical molecular orbital method, quantitative structure-activity relationships (QSARs) were derived for MTT (EC25) and for GSH (EC50). Correlation coefficients for 2- and 3-parameter QSARs of about 0.9 enable us to predict the toxicity for similar compounds. Furthermore, except in one case, predicted EC values for the uncertain endpoints were consistent with experiment. Descriptors comprising the QSARs for MTT were consistent with the biophysical mechanism of toxic response found experimentally for hydrazine derivatives. Application of our derived QSARs will assist in predicting toxicity for newly proposed propellants.

  11. Can nutrition affect chemical toxicity?

    PubMed

    Furst, A

    2002-01-01

    Universally, the general population is exposed to a variety of "toxic" substances. Some of these are from manufactured goods and some from air and water pollution. Toxins are also normally found in many foods; however, unless the exposure is overwhelming, we are many times (even unknowingly) protected by the foods we eat. A judicious choice of food will counteract noxious agents. Therefore, the diet can be a major factor in determining who does and who does not show toxic symptoms following exposure. This review will cover three aspects. The first will be on protectors against metal toxicity. For example, whereas humans can consume fish that have absorbed mercury from contaminated bay water, selenium can act as a natural antagonist for mercury poisoning. (Naturally, too much selenium itself can be detrimental!) Some vegetables can accumulate cadmium from contaminated soil, and zinc from a variety of nuts is an antagonist of cadmium toxicity. Nitrites in preserved meats can be converted into nitroamines by saliva or mild stomach acid. Vitamin C found in oranges and bell peppers can inhibit that conversion. In addition, calcium antagonizes both lead and aluminum toxicity. The second aspect is on oxidants and antioxidants. Oxidative stress can lead to some cancers, atherosclerosis, and adverse effects of aging. Antioxidants are the best protectors of the damage caused by reactive oxygen species (ROS). The most effective antioxidants are found in highly colored fruits and vegetables such as carrots, tomatoes, and berries, called carotenoids. Flavonoids (polyphenols), another class of effective antioxidants that negate ROS, may or may not be colored. The third aspect is on gaps in current knowledge. Many foods naturally contain chemicals that are, in larger concentrations, quite toxic or carcinogenic. Biotransformations (detoxification mechanisms) involving type I and type II enzymes are known. Some foods do modify these enzymes either positively or negatively

  12. High-performance gene expression module analysis tool and its application to chemical toxicity data.

    PubMed

    Fujibuchi, Wataru; Kim, Hyeryung; Okada, Yoshifumi; Taniguchi, Takeaki; Sone, Hideko

    2009-01-01

    Gene clustering is one of the main themes of data mining approaches in bioinformatics. Although it has the power to analyze gene function, interpretation of the results becomes increasingly difficult when the number of experiments (samples) exceeds hundreds or more. A new type of clustering called "biclustering," where genes and experiments are coclustered in a large-scale of gene expression data, has been extensively studied in the last decade. We have developed "SAMURAI," an original program that detects all the biclusters or "gene modules" whose genes have similar expression patterns to query profile using the ultrafast data mining algorithm called Linear-time Closed itemset Miner (LCM). Using chemical toxicity dataset from J&J rat liver experiments, we compiled an exhaustive dictionary of gene modules by searching datasets of gene modules with each chemical exposure experiment as query. Through the module analysis, we found that our program can detect up/down-regulated gene sets that significantly represent particular GO functions or KEGG pathways, thereby unraveling reactions and mechanisms common to different toxicochemical treatments of hepatocytes.

  13. CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals

    EPA Pesticide Factsheets

    Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

  14. Incorporating High-Throughput Exposure Predictions With Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing

    PubMed Central

    Wetmore, Barbara A.; Wambaugh, John F.; Allen, Brittany; Ferguson, Stephen S.; Sochaski, Mark A.; Setzer, R. Woodrow; Houck, Keith A.; Strope, Cory L.; Cantwell, Katherine; Judson, Richard S.; LeCluyse, Edward; Clewell, Harvey J.; Thomas, Russell S.; Andersen, Melvin E.

    2015-01-01

    We previously integrated dosimetry and exposure with high-throughput screening (HTS) to enhance the utility of ToxCast HTS data by translating in vitro bioactivity concentrations to oral equivalent doses (OEDs) required to achieve these levels internally. These OEDs were compared against regulatory exposure estimates, providing an activity-to-exposure ratio (AER) useful for a risk-based ranking strategy. As ToxCast efforts expand (ie, Phase II) beyond food-use pesticides toward a wider chemical domain that lacks exposure and toxicity information, prediction tools become increasingly important. In this study, in vitro hepatic clearance and plasma protein binding were measured to estimate OEDs for a subset of Phase II chemicals. OEDs were compared against high-throughput (HT) exposure predictions generated using probabilistic modeling and Bayesian approaches generated by the U.S. Environmental Protection Agency (EPA) ExpoCast program. This approach incorporated chemical-specific use and national production volume data with biomonitoring data to inform the exposure predictions. This HT exposure modeling approach provided predictions for all Phase II chemicals assessed in this study whereas estimates from regulatory sources were available for only 7% of chemicals. Of the 163 chemicals assessed in this study, 3 or 13 chemicals possessed AERs < 1 or < 100, respectively. Diverse bioactivities across a range of assays and concentrations were also noted across the wider chemical space surveyed. The availability of HT exposure estimation and bioactivity screening tools provides an opportunity to incorporate a risk-based strategy for use in testing prioritization. PMID:26251325

  15. PROLIFERATION AS A KEY EVENT IN DEVELOPMENTAL TOXICITY: "CHEMICAL SCREENING IN HUMAN NEURAL STEM CELLS USING HIGH CONTENT IMAGING

    EPA Science Inventory

    New toxicity testing approaches will rely on in vitro assays to assess chemical effects at the cellular and molecular level. Cell proliferation is imperative to normal development, and chemical disruption of this process can be detrimental to the organism. As part of an effort to...

  16. PROLIFERATION AS A KEY EVENT IN DEVELOPMENTAL TOXICITY: "CHEMICAL SCREENING IN HUMAN NEURAL STEM CELLS USING HIGH CONTENT IMAGING

    EPA Science Inventory

    New toxicity testing approaches will rely on in vitro assays to assess chemical effects at the cellular and molecular level. Cell proliferation is imperative to normal development, and chemical disruption of this process can be detrimental to the organism. As part of an effort to...

  17. Oxidative stress in chemical toxicity.

    PubMed

    Kappus, H

    1987-01-01

    The toxic effects of compounds which undergo redox cycling via enzymatic one-electron reduction are reviewed. First of all, the enzymatic reduction of these compounds leads to reactive intermediates, mainly radicals which react with oxygen, whereby superoxide anion radicals are formed. Further oxygen metabolites are hydrogen peroxide, singlet oxygen and hydroxyl radicals. The role of these oxygen metabolites in toxicity is discussed. The occurrence of lipid peroxidation during redox cycling of quinonoide compounds, e.g., adriamycin, and the possible relationship to their toxicity is critically evaluated. It is shown that iron ions play a crucial role in lipid peroxidation induced by redox cycling compounds. DNA damage by metal chelates, e.g., bleomycin, is discussed on the basis of findings that enzymatic redox cycling of a bleomycin-iron complex has been observed. The involvement of hydroxyl radicals in bleomycin-induced DNA damage occurring during redox cycling in cell nuclei is claimed. Redox cycling of other substances, e.g., aromatic amines, is discussed in relation to carcinogenesis. Other chemical groups, e.g., nitroaromatic compounds, hydroxylamines and azo compounds are included. Other targets for oxygen radical attack, e.g., proteins, are also dealt with. It is concluded that oxygen radical formation by redox cycling may be a critical event in toxic effects of several compounds if the protective mechanisms of cells are overwhelmed.

  18. High-throughput Screening of ToxCast™ Phase I Chemicals in a Mouse Embryonic Stem Cell (mESC) Assay Reveals Disruption of Potential Toxicity Pathways

    EPA Science Inventory

    Little information is available regarding the potential for many commercial chemicals to induce developmental toxicity. The mESC Adherent Cell Differentiation and Cytoxicity (ACDC) assay is a high-throughput screen used to close this data gap. Thus, ToxCast™ Phase I chemicals wer...

  19. High-throughput Screening of ToxCast™ Phase I Chemicals in a Mouse Embryonic Stem Cell (mESC) Assay Reveals Disruption of Potential Toxicity Pathways

    EPA Science Inventory

    Little information is available regarding the potential for many commercial chemicals to induce developmental toxicity. The mESC Adherent Cell Differentiation and Cytoxicity (ACDC) assay is a high-throughput screen used to close this data gap. Thus, ToxCast™ Phase I chemicals wer...

  20. High-Throughput Toxicity Testing: New Strategies for Assessing Chemical Safety

    EPA Science Inventory

    In recent years, the food industry has made progress in improving safety testing methods focused on microbial contaminants in order to promote food safety. However, food industry toxicologists must also assess the safety of food-relevant chemicals including pesticides, direct add...

  1. Estimating Toxicity-Related Biological Pathway Altering Doses for High-Throughput Chemical Risk Assessment

    EPA Science Inventory

    We describe a framework for estimating the human dose at which a chemical significantly alters a biological pathway in vivo, making use of in vitro assay data and an in vitro derived pharmacokinetic model, coupled with estimates of population variability and uncertainty. The q...

  2. High-Throughput Toxicity Testing: New Strategies for Assessing Chemical Safety

    EPA Science Inventory

    In recent years, the food industry has made progress in improving safety testing methods focused on microbial contaminants in order to promote food safety. However, food industry toxicologists must also assess the safety of food-relevant chemicals including pesticides, direct add...

  3. Estimating Toxicity-Related Biological Pathway Altering Doses for High-Throughput Chemical Risk Assessment

    EPA Science Inventory

    We describe a framework for estimating the human dose at which a chemical significantly alters a biological pathway in vivo, making use of in vitro assay data and an in vitro derived pharmacokinetic model, coupled with estimates of population variability and uncertainty. The q...

  4. Chemical toxicity of red cells.

    PubMed Central

    Piomelli, S

    1981-01-01

    Exposure to toxic chemicals may result in alterations of red cell function. In certain cases, the toxic effect requires a genetic predisposition and thus affects only a restricted number of individuals; in other instances, the toxic effect is exerted on the hematopoietic system of every person. Glucose-6-phosphate dehydrogenase deficiency is probably the most widespread genetic disorder. It is observed at highest frequency in populations from subtropical countries as a result of its selective advantage vis à vis falciparum malaria. The gene controlling this enzyme is located on the X-chromosome; thus, the defect is sex-linked. Individuals with a genetic defect of this enzyme are extremely susceptible to hemolysis, when exposed to oxidant drugs (such as certain antimalarials and sulfonamides) because of the inability of their red cells to regenerate NADPH. Lead poisoning result in profound effects on the process of heme synthesis. Among the steps most sensitive to lead toxicity are the enzyme delta-aminolevulinic acid dehydratase and the intramitochondrial step that leads to the incorporation of iron into protoporphyrin. By these mechanisms, in severe lead intoxication there is an accumulation of large amounts of delta-aminolevulinic acid (a compound with inherent neurotoxicity), and there are abnormalities of mitochondrial function in all cells of the body. Individuals living in an industrialized society are unavoidably exposed to some environmental lead. Recent evidence indicates that, even at levels of exposure which do not increase the blood lead level above values presently considered normal, abnormalities of heme synthesis are clearly detectable. PMID:7016524

  5. Toxic ratio as an indicator of the intrinsic toxicity in the assessment of persistent, bioaccumulative, and toxic chemicals.

    PubMed

    Maeder, Valérie; Escher, Beate I; Scheringer, Martin; Hungerbühler, Konrad

    2004-07-01

    Persistence, bioconcentration, and toxicity (PBT) are important hazardous properties of organic chemicals. In PBT assessments, it is desirable that the three criteria P, B, and T are independent. However, this requirement is not fulfilled if an aqueous lethal concentration (LC50) is used as T indicator because LC50 includes both bioconcentration and intrinsic toxicity. Indicators for intrinsic toxicity such asthe internal lethal concentration (ILC) are independent of a chemical's bioconcentration potential. However, ILC50 data are scarce and difficult to measure. Therefore, the toxic ratio (TR) is proposed here as an alternative. TR is defined as the ratio of a chemical's LC50 estimated from a QSAR for baseline toxicity and the experimental LC50 value. TR can also be interpreted as a measure of the ILC relative to the ILC for baseline toxicity. A TR of 10 separates specifically toxic chemicals from baseline toxicants. With some 800 chemicals, the practicability of classifying chemicals in terms of TR is demonstrated. Employing TR as toxicity indicator leads to different T scores for 30% of the chemicals studied. The baseline toxicity of hydrophobic compounds with TR < 10 does not receive a high T score but is still indicated by a high B score. The toxicity of specifically toxic hydrophilic substances is given additional emphasis by high TR values. These classification changes require that the interpretation of the B and T dimensions in PBT assessments is redefined.

  6. The Toxicity Data Landscape for Environmental Chemicals

    PubMed Central

    Judson, Richard; Richard, Ann; Dix, David J.; Houck, Keith; Martin, Matthew; Kavlock, Robert; Dellarco, Vicki; Henry, Tala; Holderman, Todd; Sayre, Philip; Tan, Shirlee; Carpenter, Thomas; Smith, Edwin

    2009-01-01

    Objective Thousands of chemicals are in common use, but only a portion of them have undergone significant toxicologic evaluation, leading to the need to prioritize the remainder for targeted testing. To address this issue, the U.S. Environmental Protection Agency (EPA) and other organizations are developing chemical screening and prioritization programs. As part of these efforts, it is important to catalog, from widely dispersed sources, the toxicology information that is available. The main objective of this analysis is to define a list of environmental chemicals that are candidates for the U.S. EPA screening and prioritization process, and to catalog the available toxicology information. Data sources We are developing ACToR (Aggregated Computational Toxicology Resource), which combines information for hundreds of thousands of chemicals from > 200 public sources, including the U.S. EPA, National Institutes of Health, Food and Drug Administration, corresponding agencies in Canada, Europe, and Japan, and academic sources. Data extraction ACToR contains chemical structure information; physical–chemical properties; in vitro assay data; tabular in vivo data; summary toxicology calls (e.g., a statement that a chemical is considered to be a human carcinogen); and links to online toxicology summaries. Here, we use data from ACToR to assess the toxicity data landscape for environmental chemicals. Data synthesis We show results for a set of 9,912 environmental chemicals being considered for analysis as part of the U.S. EPA ToxCast screening and prioritization program. These include high-and medium-production-volume chemicals, pesticide active and inert ingredients, and drinking water contaminants. Conclusions Approximately two-thirds of these chemicals have at least limited toxicity summaries available. About one-quarter have been assessed in at least one highly curated toxicology evaluation database such as the U.S. EPA Toxicology Reference Database, U.S. EPA Integrated

  7. High-content imaging-based BAC-GFP toxicity pathway reporters to assess chemical adversity liabilities.

    PubMed

    Wink, Steven; Hiemstra, Steven; Herpers, Bram; van de Water, Bob

    2017-03-01

    Adaptive cellular stress responses are paramount in the healthy control of cell and tissue homeostasis and generally activated during toxicity in a chemical-specific manner. Here, we established a platform containing a panel of distinct adaptive stress response reporter cell lines based on BAC-transgenomics GFP tagging in HepG2 cells. Our current panel of eleven BAC-GFP HepG2 reporters together contains (1) upstream sensors, (2) downstream transcription factors and (3) their respective target genes, representing the oxidative stress response pathway (Keap1/Nrf2/Srxn1), the unfolded protein response in the endoplasmic reticulum (Xbp1/Atf4/BiP/Chop) and the DNA damage response (53bp1/p53/p21). Using automated confocal imaging and quantitative single-cell image analysis, we established that all reporters allowed the time-resolved, sensitive and mode-of-action-specific activation of the individual BAC-GFP reporter cell lines as defined by a panel of pathway-specific training compounds. Implementing the temporal pathway activity information increased the discrimination of training compounds. For a set of >30 hepatotoxicants, the induction of Srxn1, BiP, Chop and p21 BAC-GFP reporters correlated strongly with the transcriptional responses observed in cryopreserved primary human hepatocytes. Together, our data indicate that a phenotypic adaptive stress response profiling platform will allow a high throughput and time-resolved classification of chemical-induced stress responses, thus assisting in the future mechanism-based safety assessment of chemicals.

  8. Toxic Release Inventory Chemicals by Groupings

    EPA Pesticide Factsheets

    The Toxics Release Inventory (TRI) makes available information for more than 600 toxic chemicals that are being used, manufactured, treated, transported, or released into the environment since 1987. EPA makes changes (additions, deletions, or changes in definition) to the TRI chemical list. As a result, the TRI list of reportable toxic chemicals can vary from year to year. EPA created groupings such as the core chemical lists (of 1988, 1991, 1995, 1998, 2000, and 2001) to facilitate year-to-year comparison based on a consistent set of reporting requirements and assure that changes in TRI release or other waste management amounts do not reflect the addition, deletion, or change in definition of reportable chemicals. EPA also created groupings of specific chemicals of interest by categories such as Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), Hazardous Air Pollutants (HAPs), Metals, Newly Added TRI Chemicals in 1995, Occupational Safety and Health Administration (OSHA, Carcinogens), Persistent Bioaccumulative and Toxic (PBT) Chemicals, and Priority Chemicals.

  9. Exploitation of deep-sea resources: the urgent need to understand the role of high pressure in the toxicity of chemical pollutants to deep-sea organisms.

    PubMed

    Mestre, Nélia C; Calado, Ricardo; Soares, Amadeu M V M

    2014-02-01

    The advent of industrial activities in the deep sea will inevitably expose deep-sea organisms to potentially toxic compounds. Although international regulations require environmental risk assessment prior to exploitation activities, toxicity tests remain focused on shallow-water model species. Moreover, current tests overlook potential synergies that may arise from the interaction of chemicals with natural stressors, such as the high pressures prevailing in the deep sea. As pressure affects chemical reactions and the physiology of marine organisms, it will certainly affect the toxicity of pollutants arising from the exploitation of deep-sea resources. We emphasize the need for environmental risk assessments based on information generated from ecotoxicological trials that mimic, as close as possible, the deep-sea environment, with emphasis to a key environmental factor - high hydrostatic pressure.

  10. America's Poisoned Playgrounds: Children and Toxic Chemicals.

    ERIC Educational Resources Information Center

    Freedberg, Louis

    Next to chemical and farm workers, today's children are at the greatest risk from toxic chemicals. Through their normal play activities, children are exposed to a frightening array of toxic hazards, including lead, pesticides, arsenic, and unknown dangers from abandoned landfills and warehouses. Through a series of documented examples, the author…

  11. America's Poisoned Playgrounds: Children and Toxic Chemicals.

    ERIC Educational Resources Information Center

    Freedberg, Louis

    Next to chemical and farm workers, today's children are at the greatest risk from toxic chemicals. Through their normal play activities, children are exposed to a frightening array of toxic hazards, including lead, pesticides, arsenic, and unknown dangers from abandoned landfills and warehouses. Through a series of documented examples, the author…

  12. Identification of Chemical Toxicity Using Ontology Information of Chemicals.

    PubMed

    Jiang, Zhanpeng; Xu, Rui; Dong, Changchun

    2015-01-01

    With the advance of the combinatorial chemistry, a large number of synthetic compounds have surged. However, we have limited knowledge about them. On the other hand, the speed of designing new drugs is very slow. One of the key causes is the unacceptable toxicities of chemicals. If one can correctly identify the toxicity of chemicals, the unsuitable chemicals can be discarded in early stage, thereby accelerating the study of new drugs and reducing the R&D costs. In this study, a new prediction method was built for identification of chemical toxicities, which was based on ontology information of chemicals. By comparing to a previous method, our method is quite effective. We hope that the proposed method may give new insights to study chemical toxicity and other attributes of chemicals.

  13. Ranking chemicals based on chronic toxicity data.

    PubMed

    De Rosa, C T; Stara, J F; Durkin, P R

    1985-12-01

    During the past 3 years, EPA's ECAO/Cincinnati has developed a method to rank chemicals based on chronic toxicity data. This ranking system reflects two primary attributes of every chemical: the minimum effective dose and the type of effect elicited at that dose. The purpose for developing this chronic toxicity ranking system was to provide the EPA with the technical background required to adjust the RQs of hazardous substances designated in Section 101(14) of CERCLA or "Superfund." This approach may have applications to other areas of interest to the EPA and other regulatory agencies where ranking of chemicals based on chronic toxicity is desired.

  14. Raising awareness of new psychoactive substances: chemical analysis and in vitro toxicity screening of 'legal high' packages containing synthetic cathinones.

    PubMed

    Araújo, Ana Margarida; Valente, Maria João; Carvalho, Márcia; Dias da Silva, Diana; Gaspar, Helena; Carvalho, Félix; de Lourdes Bastos, Maria; Guedes de Pinho, Paula

    2015-05-01

    The world's status quo on recreational drugs has dramatically changed in recent years due to the rapid emergence of new psychoactive substances (NPS), represented by new narcotic or psychotropic drugs, in pure form or in preparation, which are not controlled by international conventions, but that may pose a public health threat comparable with that posed by substances listed in these conventions. These NPS, also known as 'legal highs' or 'smart drugs', are typically sold via Internet or 'smartshops' as legal alternatives to controlled substances, being announced as 'bath salts' and 'plant feeders' and is often sought after for consumption especially among young people. Although NPS have the biased reputation of being safe, the vast majority has hitherto not been tested and several fatal cases have been reported, namely for synthetic cathinones, with pathological patterns comparable with amphetamines. Additionally, the unprecedented speed of appearance and distribution of the NPS worldwide brings technical difficulties in the development of analytical procedures and risk assessment in real time. In this study, 27 products commercialized as 'plant feeders' were chemically characterized by gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. It was also evaluated, for the first time, the in vitro hepatotoxic effects of individual synthetic cathinones, namely methylone, pentedrone, 4-methylethcathinone (4-MEC) and 3,4-methylenedioxypyrovalerone (MDPV). Two commercial mixtures ('Bloom' and 'Blow') containing mainly cathinone derivatives were also tested, and 3,4-methylenedioxymethamphetamine (MDMA) was used as the reference drug. The study allowed the identification of 19 compounds, showing that synthetic cathinones are the main active compounds present in these products. Qualitative and quantitative variability was found in products sold with the same trade name in matching or different 'smartshops'. In the toxicity studies performed in

  15. Toxicity challenges in environmental chemicals: Prediction of ...

    EPA Pesticide Factsheets

    Physiologically based pharmacokinetic (PBPK) models bridge the gap between in vitro assays and in vivo effects by accounting for the adsorption, distribution, metabolism, and excretion of xenobiotics, which is especially useful in the assessment of human toxicity. Quantitative structure-activity relationships (QSAR) serve as a vital tool for the high-throughput prediction of chemical-specific PBPK parameters, such as the fraction of a chemical unbound by plasma protein (Fub). The presented work explores the merit of utilizing experimental pharmaceutical Fub data for the construction of a universal QSAR model, in order to compensate for the limited range of high-quality experimental Fub data for environmentally relevant chemicals, such as pollutants, pesticides, and consumer products. Independent QSAR models were constructed with three machine-learning algorithms, k nearest neighbors (kNN), random forest (RF), and support vector machine (SVM) regression, from a large pharmaceutical training set (~1000) and assessed with independent test sets of pharmaceuticals (~200) and environmentally relevant chemicals in the ToxCast program (~400). Small descriptor sets yielded the optimal balance of model complexity and performance, providing insight into the biochemical factors of plasma protein binding, while preventing over fitting to the training set. Overlaps in chemical space between pharmaceutical and environmental compounds were considered through applicability of do

  16. Integration of High-Throughput Screening Data with Dosimetry and Human Exposure in the Toxicity Assessment of Environmental Chemicals

    EPA Science Inventory

    High-throughput in vitro screening and computational tools provide government an efficient way to identify those chemicals that warrant further testing while conserving limited testing resources. Incorporation of kinetic and exposure information should provide a more meaningful i...

  17. THE TOXCAST PROGRAM FOR PRIORITIZING TOXICITY TESTING OF ENVIRONMENTAL CHEMICALS

    EPA Science Inventory

    The United States Environmental Protection Agency (EPA) is developing methods for utilizing computational chemistry, high-throughput screening (HTS) and various toxicogenomic technologies to predict potential for toxicity and prioritize limited testing resources towards chemicals...

  18. THE TOXCAST PROGRAM FOR PRIORITIZING TOXICITY TESTING OF ENVIRONMENTAL CHEMICALS

    EPA Science Inventory

    The United States Environmental Protection Agency (EPA) is developing methods for utilizing computational chemistry, high-throughput screening (HTS) and various toxicogenomic technologies to predict potential for toxicity and prioritize limited testing resources towards chemicals...

  19. Toxic Chemicals Use in School Labs Examined.

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1982

    1982-01-01

    The Consumer Product Safety Commission will recommend an information network to inform students and teachers of current toxicity evaluations of chemicals and of possible use of less hazardous substitutes. Lists names of 33 suspected carcinogens and 11 suspected teratogens. (SK)

  20. Toxic Chemicals Use in School Labs Examined.

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1982

    1982-01-01

    The Consumer Product Safety Commission will recommend an information network to inform students and teachers of current toxicity evaluations of chemicals and of possible use of less hazardous substitutes. Lists names of 33 suspected carcinogens and 11 suspected teratogens. (SK)

  1. CHEMICAL STRUCTURE INDEXING OF TOXICITY DATA ON ...

    EPA Pesticide Factsheets

    Standardized chemical structure annotation of public toxicity databases and information resources is playing an increasingly important role in the 'flattening' and integration of diverse sets of biological activity data on the Internet. This review discusses public initiatives that are accelerating the pace of this transformation, with particular reference to toxicology-related chemical information. Chemical content annotators, structure locator services, large structure/data aggregator web sites, structure browsers, International Union of Pure and Applied Chemistry (IUPAC) International Chemical Identifier (InChI) codes, toxicity data models and public chemical/biological activity profiling initiatives are all playing a role in overcoming barriers to the integration of toxicity data, and are bringing researchers closer to the reality of a mineable chemical Semantic Web. An example of this integration of data is provided by the collaboration among researchers involved with the Distributed Structure-Searchable Toxicity (DSSTox) project, the Carcinogenic Potency Project, projects at the National Cancer Institute and the PubChem database. Standardizing chemical structure annotation of public toxicity databases

  2. Differential Toxicity Characterization of Green Alternative Chemicals

    EPA Science Inventory

    Assessing the toxicity of a chemical across all possible disease domains and understanding its dose- response behavior cost millions to tens of millions of dollars per chemical, and can take years to decades to evaluate fully. This expense and the lack of regulatory requirements ...

  3. Differential Toxicity Characterization of Green Alternative Chemicals

    EPA Science Inventory

    Assessing the toxicity of a chemical across all possible disease domains and understanding its dose- response behavior cost millions to tens of millions of dollars per chemical, and can take years to decades to evaluate fully. This expense and the lack of regulatory requirements ...

  4. Toxico-Cheminformatics: New and Expanding Public Resources to Support Chemical Toxicity Assessments

    EPA Science Inventory

    High-throughput screening (HTS) technologies, along with efforts to improve public access to chemical toxicity information resources and to systematize older toxicity studies, have the potential to significantly improve information gathering efforts for chemical assessments and p...

  5. Toxico-Cheminformatics: New and Expanding Public Resources to Support Chemical Toxicity Assessments

    EPA Science Inventory

    High-throughput screening (HTS) technologies, along with efforts to improve public access to chemical toxicity information resources and to systematize older toxicity studies, have the potential to significantly improve information gathering efforts for chemical assessments and p...

  6. [Arsine: an unknown industrial chemical toxic].

    PubMed

    Plantamura, J; Dorandeu, F; Burnat, P; Renard, C

    2011-07-01

    Arsines family includes many compounds with various toxicities. Arsenic trihydride or arsine is the most toxic form of arsenic. Powerful haemolytic gas, it has never been used as a chemical weapon because its toxicity is not immediate and it is non persistent. However, cases of industrial poisoning with arsine are still identified in spite of a strict regulation at work. It is also identified as a potential toxic of chemical terrorism. This agent, of which the mechanism of action is still not well defined, is badly recognized because of intoxications rarity. However, fast detection means are available. Health professionals and especially those who are involved in piratox plan need to learn to recognize arsine intoxication (hematuria, oliguria, haemolytic anemia) in order to provide early, specific treatment and avoid damages. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  7. Management of chemical toxic wastes

    SciTech Connect

    Gold, L.

    1982-05-25

    Two regimes of vertical shaft furnace operation can be employed to slag encapsulate hazardous chemical wastes. One of these is similar to a method applicable to radioactive wastes, involving the pouring of hot molten slag from a coal reactor over the hazardous matter contained in a suitable designed crucible. The other method is especially appropriate for the treatment of chemical wastes that have become mixed with a great deal of soil or other diluent as must be handled as in the case of the love canal incident. It consists of feeding the contaminated solid mass into the coal reactor with a predetermined amount of coal and limestone that will still admit an adequate heat balance to generate a carefully tailored slag to incorporate the reacted waste feedstock.

  8. DOE contractor's meeting on chemical toxicity

    SciTech Connect

    Not Available

    1987-01-01

    The Office of Health and Environmental Research (OHER) is required to determine the potential health and environmental effects associated with energy production and use. To ensure appropriate communication among investigators and scientific disciplines that these research studies represent, OHER has sponsored workshops. This document provides a compilation of activities at the Third Annual DOE/OHER Workshop. This year's workshop was broadened to include all OHER activities identified as within the chemical effects area. The workshop consisted of eight sessions entitled Isolation and Detection of Toxic chemicals; Adduct Formation and Repair; Chemical Toxicity (Posters); Metabolism and Genotoxicity; Inhalation Toxicology; Gene Regulation; Metals Toxicity; and Biological Mechanisms. This document contains abstracts of the information presented by session.

  9. The problem of current toxic chemicals management.

    PubMed

    Tickner, Joel; Geiser, Ken

    2004-01-01

    In this article, we explore the limitations of current chemicals management policies worldwide and the evolution of new European, International and U.S. policies to address the problem of toxic chemicals control. It is becoming increasingly apparent that current chemicals management policies in Europe and the United States are inadequate. There is a general lack of toxicity and exposure information on chemicals in commerce and the vast majority of chemicals were considered safe until proven guilty in legislation. Governments must then prove each chemical is dangerous through a slow and resource-intensive risk assessment process. For more than a decade, Nordic countries, such as Denmark and Sweden, have actively promoted integrated chemicals policies to address contamination of critical waterways. They have successfully used a variety of voluntary and mandatory policy tools, such as education, procurement, lists of chemicals of concern, eco-labeling, research and development on safer substitutes, and chemical phase-out requirements, to encourage companies using chemicals to reduce their reliance on harmful substances and to develop safer substitutes. While previously isolated to particular countries, innovative and exciting European-wide policies to promote sustainable chemicals management are now moving forward, including the recently published draft Registration, Evaluation and Authorization of CHemicals (REACH) policy of the European Union. A sweeping change in chemicals management policies in Europe is inevitable and it will ultimately affect manufacturers in the U.S. and globally. The European movement provides an opportunity to initiate a discussion on integrated chemicals policy in the U.S. where some innovative initiatives already are underway.

  10. Toxic chemical considerations for tank farm releases

    SciTech Connect

    Van Keuren, J.C.; Davis, J.S., Westinghouse Hanford

    1996-08-01

    This topical report contains technical information used to determine the accident consequences of releases of toxic chemical and gases for the Tank Farm Final Safety Analysis report (FSAR).It does not provide results for specific accident scenarios but does provide information for use in those calculations including chemicals to be considered, chemical concentrations, chemical limits and a method of summing the fractional contributions of each chemical. Tank farm composites evaluated were liquids and solids for double shell tanks, single shell tanks, all solids,all liquids, headspace gases, and 241-C-106 solids. Emergency response planning guidelines (ERPGs) were used as the limits.Where ERPGs were not available for the chemicals of interest, surrogate ERPGs were developed. Revision 2 includes updated sample data, an executive summary, and some editorial revisions.

  11. CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals - Detailed Conceptual Diagram

    EPA Pesticide Factsheets

    Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

  12. CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals - Simple Conceptual Diagram

    EPA Pesticide Factsheets

    Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

  13. Comparative toxicity of chemicals to earthworms

    SciTech Connect

    Callahan, C.A.; Shirazi, M.A. ); Neuhauser, E.F. )

    1994-02-01

    The concentration-response (mortality) relationships of four species of earthworms, Eisenia fetida (Savigny), Allolobophora tuberculata (Eisen), Eudrilus eugeniae (Kinberg), and Perionyx excavatus (Perrier) are summarized for 62 chemicals and two test protocols. A Weibull function is used to summarize these data for each chemical in terms of sensitivity and toxicity, in addition to the LC50. The estimation of the Weibull parameters a and k summarize the entire concentration-response relationship. This technique should be applicable to a variety of testing protocols with different species whenever the goal is summarizing the shape of the concentration-response curves to fully evaluate chemical impact on organisms. In some cases for these data four orders of magnitude separate LC50s of the soil test and the contact test for the same chemical and species. All four species appear to be similar in range of toxicity and tolerance to these chemicals, suggesting that Eisenia fetida and may be representative of these four species and these chemicals.

  14. [Chemical incidents and gathering information on toxicity].

    PubMed

    Yamamoto, Miyako; Morikawa, Kaoru

    2006-12-01

    Major cases of chemical incidents and information on chemical agents and chemical terrorist attacks are outlined. Since the late 1990s, major incidents occurred consecutively, such as two cases of sarin attack in 1994 and 1995, an oil spill from a Russian oil tanker in the Japan Sea in 1997, arsenic poisoning in Wakayama in 1998, the criticality incident at Tokai-Mura in 1999 in Japan, and terrorist attacks on September 11, 2001, in New York. The importance of crisis management and cooperation among relevant organizations has been emphasized. To provide information for an appropriate and quick response in emergencies, we prepared a Web portal site for information on chemicals including chemical agents, a chemical incident database, and links to relevant Web sites. In intentional cases of poisoning caused by toxic chemicals in Japan, 111 cases were collected mainly from a newspaper database (1984-1999). Many copy-cat poisonings occurred, especially in 1984-1985 and in 1998 just after an arsenic poisoning incident in Wakayama. Many cases occurred in the laboratories of institutes, universities, and hospitals where various types of chemicals are used.

  15. Toxic Industrial Chemicals: A Future Weapons of Mass Destruction Threat

    DTIC Science & Technology

    2007-11-02

    dependent on factors, such as temperature , pressure, and wind speed (US Army 1990; 1994; and 1998a). In addition to CW agents’ toxicities, their chemical...expected to be at especially high risk of shigellosis, malaria, sandfly fever, and cutaneous leishmaniasis (Quin 1992). Studies conducted since the war

  16. 40 CFR 372.45 - Notification about toxic chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 28 2011-07-01 2011-07-01 false Notification about toxic chemicals..., EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS TOXIC CHEMICAL RELEASE REPORTING: COMMUNITY RIGHT-TO-KNOW Supplier Notification Requirements § 372.45 Notification about toxic chemicals. (a) Except...

  17. 40 CFR 372.45 - Notification about toxic chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Notification about toxic chemicals..., EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS TOXIC CHEMICAL RELEASE REPORTING: COMMUNITY RIGHT-TO-KNOW Supplier Notification Requirements § 372.45 Notification about toxic chemicals. (a) Except...

  18. 40 CFR 372.45 - Notification about toxic chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Notification about toxic chemicals..., EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS TOXIC CHEMICAL RELEASE REPORTING: COMMUNITY RIGHT-TO-KNOW Supplier Notification Requirements § 372.45 Notification about toxic chemicals. (a) Except...

  19. 40 CFR 372.45 - Notification about toxic chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 28 2014-07-01 2014-07-01 false Notification about toxic chemicals..., EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS TOXIC CHEMICAL RELEASE REPORTING: COMMUNITY RIGHT-TO-KNOW Supplier Notification Requirements § 372.45 Notification about toxic chemicals. (a) Except...

  20. 48 CFR 52.223-14 - Toxic Chemical Release Reporting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Toxic Chemical Release....223-14 Toxic Chemical Release Reporting. As prescribed in 23.906(b), insert the following clause: Toxic Chemical Release Reporting (AUG 2003) (a) Unless otherwise exempt, the Contractor, as owner...

  1. 40 CFR 372.45 - Notification about toxic chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Notification about toxic chemicals..., EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS TOXIC CHEMICAL RELEASE REPORTING: COMMUNITY RIGHT-TO-KNOW Supplier Notification Requirements § 372.45 Notification about toxic chemicals. (a) Except...

  2. 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...

  3. 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...

  4. Sampling the stratum corneum for toxic chemicals.

    PubMed

    Coman, Garrett; Blickenstaff, Nicholas R; Blattner, Collin M; Andersen, Rosa; Maibach, Howard I

    2014-01-01

    Dermal exposure is an important pathway in environmental health. Exposure comes from contaminated water, soil, treated surfaces, textiles, aerosolized chemicals, and agricultural products. It can occur in homes, schools, play areas, and work settings in the form of industrial sources, consumer products, or hazardous wastes. Dermal exposure is most likely to occur through contact with liquids, water, soil, sediment, and contaminated surfaces. The ability to detect and measure exposure to toxic materials on the skin is an important environmental health issue. The stratum corneum is the skin's first and principal barrier layer of protection from the outside world. It has a complex structure that can effectively protect against a wide variety of physical, chemical, and biological contaminants. However, there are a variety of chemical agents that can damage the stratum corneum and the underlying epidermis, dermis and subcutis, and/or enter systemic circulation through the skin. There are numerous ways of sampling the stratum corneum for these toxic materials like abrasion techniques, biopsy, suction blistering, imaging, washing, wipe sampling, tape stripping, and spot testing. Selecting a method likely depends on the particular needs of the situation. Hence, there is a need to review practical considerations for their use in sampling the stratum corneum for toxins.

  5. Incorporating High-Throughput Exposure Predictions with Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing

    EPA Science Inventory

    We previously integrated dosimetry and exposure with high-throughput screening (HTS) to enhance the utility of ToxCast™ HTS data by translating in vitro bioactivity concentrations to oral equivalent doses (OEDs) required to achieve these levels internally. These OEDs were compare...

  6. Incorporating High-Throughput Exposure Predictions with Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing

    EPA Science Inventory

    We previously integrated dosimetry and exposure with high-throughput screening (HTS) to enhance the utility of ToxCast™ HTS data by translating in vitro bioactivity concentrations to oral equivalent doses (OEDs) required to achieve these levels internally. These OEDs were compare...

  7. Chemical air pollutants and otorhinolaryngeal toxicity

    SciTech Connect

    Bisesi, M.S.; Rubin, A.M. . Occupational Health and Otolaryngology)

    1994-03-01

    Air pollution and the specific issue regarding the impact of airborne chemical agents to human health are familiar topics to most members of the environmental health science and environmental medicine communities. Some aspects, however, have received relatively less attention. Much has been published regarding the impact of air pollutants on the human upper and lower respiratory system, including interaction with the rhinologic (nasal) system. Relatively fewer data have been published, however, regarding the potential impact of air pollutants in reference specifically to the otologic (auditory and vestibular) and the laryngeal (larynx) system. Adverse impact to the ears, nose and throat, referred to as the otorhinolaryngeal system'', warrants attention as an important environmental health issue. Toxic interactions from exposure to many chemical air pollutants not only causes potential respiratory irritation and lung disease, but can also result in impaired hearing, balance, sense of smell, taste, and speech due to interaction with related target systems. This may be significant to environmental health risk assessment of chemical air pollutants if multi-target site models are considered.

  8. Integrated Proteomic Approaches for Understanding Toxicity of Environmental Chemicals

    EPA Science Inventory

    To apply quantitative proteomic analysis to the evaluation of toxicity of environmental chemicals, we have developed an integrated proteomic technology platform. This platform has been applied to the analysis of the toxic effects and pathways of many important environmental chemi...

  9. Integrated Proteomic Approaches for Understanding Toxicity of Environmental Chemicals

    EPA Science Inventory

    To apply quantitative proteomic analysis to the evaluation of toxicity of environmental chemicals, we have developed an integrated proteomic technology platform. This platform has been applied to the analysis of the toxic effects and pathways of many important environmental chemi...

  10. Optical detection of chemical warfare agents and toxic industrial chemicals

    NASA Astrophysics Data System (ADS)

    Webber, Michael E.; Pushkarsky, Michael B.; Patel, C. Kumar N.

    2004-12-01

    We present an analytical model evaluating the suitability of optical absorption based spectroscopic techniques for detection of chemical warfare agents (CWAs) and toxic industrial chemicals (TICs) in ambient air. The sensor performance is modeled by simulating absorption spectra of a sample containing both the target and multitude of interfering species as well as an appropriate stochastic noise and determining the target concentrations from the simulated spectra via a least square fit (LSF) algorithm. The distribution of the LSF target concentrations determines the sensor sensitivity, probability of false positives (PFP) and probability of false negatives (PFN). The model was applied to CO2 laser based photoacosutic (L-PAS) CWA sensor and predicted single digit ppb sensitivity with very low PFP rates in the presence of significant amount of interferences. This approach will be useful for assessing sensor performance by developers and users alike; it also provides methodology for inter-comparison of different sensing technologies.

  11. Policy Statement on a New Chemicals Category for Persistent, Bioaccumulative, and Toxic (PBT) Chemicals

    EPA Pesticide Factsheets

    On November 4, 1999, EPA issued its policy statement on a category for Persistent Bioaccumulative and Toxic (PBT) new chemicals. The statement provides guidance criteria for persistence, bioaccumulation, and toxicity for new chemicals.

  12. Using Chemical-Induced Gene Expression in Cultured Human Cells to Predict Chemical Toxicity.

    PubMed

    Liu, Ruifeng; Yu, Xueping; Wallqvist, Anders

    2016-11-21

    Chemical toxicity is conventionally evaluated in animal models. However, animal models are resource intensive; moreover, they face ethical and scientific challenges because the outcomes obtained by animal testing may not correlate with human responses. To develop an alternative method for assessing chemical toxicity, we investigated the feasibility of using chemical-induced genome-wide expression changes in cultured human cells to predict the potential of a chemical to cause specific organ injuries in humans. We first created signatures of chemical-induced gene expression in a vertebral-cancer of the prostate cell line for ∼15,000 chemicals tested in the US National Institutes of Health Library of Integrated Network-Based Cellular Signatures program. We then used the signatures to create naı̈ve Bayesian prediction models for chemical-induced human liver cholestasis, interstitial nephritis, and long QT syndrome. Detailed cross-validation analyses indicated that the models were robust with respect to false positives and false negatives in the samples we used to train the models and could predict the likelihood that chemicals would cause specific organ injuries. In addition, we performed a literature search for drugs and dietary supplements, not formally categorized as causing organ injuries in humans but predicted by our models to be most likely to do so. We found a high percentage of these compounds associated with case reports of relevant organ injuries, lending support to the idea that in vitro cell-based experiments can be used to predict the toxic potential of chemicals. We believe that this approach, combined with a robust technique to model human exposure to chemicals, may serve as a promising alternative to animal-based chemical toxicity assessment.

  13. Toxicity testing in the 21st century beyond environmental chemicals.

    PubMed

    Rovida, Costanza; Asakura, Shoji; Daneshian, Mardas; Hofman-Huether, Hana; Leist, Marcel; Meunier, Leo; Reif, David; Rossi, Anna; Schmutz, Markus; Valentin, Jean-Pierre; Zurlo, Joanne; Hartung, Thomas

    2015-01-01

    After the publication of the report titled Toxicity Testing in the 21st Century - A Vision and a Strategy, many initiatives started to foster a major paradigm shift for toxicity testing - from apical endpoints in animal-based tests to mechanistic endpoints through delineation of pathways of toxicity (PoT) in human cell based systems. The US EPA has funded an important project to develop new high throughput technologies based on human cell based in vitro technologies. These methods are currently being incorporated into the chemical risk assessment process. In the pharmaceutical industry, the efficacy and toxicity of new drugs are evaluated during preclinical investigations that include drug metabolism, pharmacokinetics, pharmacodynamics and safety toxicology studies. The results of these studies are analyzed and extrapolated to predict efficacy and potential adverse effects in humans. However, due to the high failure rate of drugs during the clinical phases, a new approach for a more predictive assessment of drugs both in terms of efficacy and adverse effects is getting urgent. The food industry faces the challenge of assessing novel foods and food ingredients for the general population, while using animal safety testing for extrapolation purposes is often of limited relevance. The question is whether the latest paradigm shift proposed by the Tox21c report for chemicals may provide a useful tool to improve the risk assessment approach also for drugs and food ingredients.

  14. The chemical exposure toxicity space (CETS) model: Displaying exposure time, aqueous and organic concentration, activity, and onset of toxicity.

    PubMed

    Mackay, Donald; Celsie, Alena K D; Parnis, J Mark; McCarty, Lynn S; Arnot, Jon A; Powell, David E

    2017-05-01

    A 1-compartment toxicokinetic model is used to characterize the chemical exposure toxicity space (CETS), providing a novel graphic tool that can aid in the design of aquatic toxicity tests for fish and for interpreting their results. The graph depicts the solution to the differential equation describing the uptake kinetics of a chemical by a modeled fish under conventional bioassay conditions. The model relates the exposure concentration in the water to a dimensionless time and the onset of toxicity as determined by an estimated or assumed critical body residue or incipient lethal aqueous concentration. These concentration graphs are specific to each chemical and exposure and organism parameters and clearly demonstrate differences in toxicity between chemicals and how factors such as hydrophobicity influence the toxic endpoint. The CETS plots can also be used to assess bioconcentration test conditions to ensure that concentrations are well below toxic levels. Illustrative applications are presented using a recent set of high-quality toxicity data. Conversion of concentrations to chemical activities in the plots enables results for different baseline toxicants to be superimposed. For chemicals that have different modes of toxic action, the increased toxicity then becomes apparent. Implications for design and interpretation of aquatic toxicity tests are discussed. The model, and pictorial visualization of the time-course of aquatic toxicity tests, may contribute to improvements in test design, implementation, and interpretation, and to reduced animal usage. Environ Toxicol Chem 2017;36:1389-1396. © 2016 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC. © 2016 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.

  15. GENE INDUCTION STUDIES AND TOXICITY OF CHEMICAL MIXTURES

    EPA Science Inventory

    As part of its mixtures program the Agency for Toxic Substances and Disease Registry (ATSDR) supports in vitro and limited in vivo toxicity testing to further our understanding of the toxicity and health effects of chemical mixtures. There are increasing concerns that environment...

  16. GENE INDUCTION STUDIES AND TOXICITY OF CHEMICAL MIXTURES

    EPA Science Inventory

    As part of its mixtures program the Agency for Toxic Substances and Disease Registry (ATSDR) supports in vitro and limited in vivo toxicity testing to further our understanding of the toxicity and health effects of chemical mixtures. There are increasing concerns that environment...

  17. Exposure Science for Chemical Prioritization and Toxicity Testing

    EPA Science Inventory

    Currently, a significant research effort is underway to apply new technologies to screen and prioritize chemicals for toxicity testing as well as to improve understanding of toxicity pathways (Dix et al. 2007, Toxicol Sci; NRC, 2007, Toxicity Testing in the 21st Century; Collins ...

  18. Toxic Chemical Exposure in Schools: Our Children at Risk.

    ERIC Educational Resources Information Center

    Sterling, Peter; Paquette, Nicole

    Asserting that toxic chemicals can be found throughout school grounds in pesticides, building materials, school supplies, cleaning products, office equipment, and personal care products, this reports details the prevalence of toxic chemicals within schools and recommends methods for reducing exposure. Following an executive summary, the report…

  19. Reactive chromophores for sensitive and selective detection of chemical warfare agents and toxic industrial chemicals

    NASA Astrophysics Data System (ADS)

    Frye-Mason, Greg; Leuschen, Martin; Wald, Lara; Paul, Kateri; Hancock, Lawrence F.

    2005-05-01

    A reactive chromophore developed at MIT exhibits sensitive and selective detection of surrogates for G-class nerve agents. This reporter acts by reacting with the agent to form an intermediate that goes through an internal cyclization reaction. The reaction locks the molecule into a form that provides a strong fluorescent signal. Using a fluorescent sensor platform, Nomadics has demonstrated rapid and sensitive detection of reactive simulants such as diethyl chloro-phosphate (simulant for sarin, soman, and related agents) and diethyl cyanophosphate (simulant for tabun). Since the unreacted chromophore does not fluoresce at the excitation wavelength used for the cyclized reporter, the onset of fluo-rescence can be easily detected. This fluorescence-based detection method provides very high sensitivity and could enable rapid detection at permissible exposure levels. Tests with potential interferents show that the reporter is very selective, with responses from only a few highly toxic, electrophilic chemicals such as phosgene, thionyl chloride, and strong acids such as HF, HCl, and nitric acid. Dimethyl methyl phosphonate (DMMP), a common and inactive simu-lant for other CW detectors, is not reactive enough to generate a signal. The unique selectivity to chemical reactivity means that a highly toxic and hazardous chemical is present when the reporter responds and illustrates that this sensor can provide very low false alarm rates. Current efforts focus on demonstrating the sensitivity and range of agents and toxic industrial chemicals detected with this reporter as well as developing additional fluorescent reporters for a range of chemical reactivity classes. The goal is to produce a hand-held sensor that can sensitively detect a broad range of chemical warfare agent and toxic industrial chemical threats.

  20. Integrated modeling systems to assess exposure and toxicity of chemicals in support of aquatic ecological risk assessment of methodologically challenging chemicals

    EPA Science Inventory

    From an exposure assessment perspective, persistent, bioaccumulative and toxic chemicals (PBTs) are some of the most challenging chemicals facing environmental decision makers today. Due to their general physico-chemical properties [e.g., high octanol-water partition coefficien...

  1. Integrated modeling systems to assess exposure and toxicity of chemicals in support of aquatic ecological risk assessment of methodologically challenging chemicals

    EPA Science Inventory

    From an exposure assessment perspective, persistent, bioaccumulative and toxic chemicals (PBTs) are some of the most challenging chemicals facing environmental decision makers today. Due to their general physico-chemical properties [e.g., high octanol-water partition coefficien...

  2. DETECTION OF TOXICANT(S) ON BUILDING SURFACES FOLLOWING CHEMICAL ATTACK

    EPA Science Inventory

    A critical step prior to reoccupation of any facility following a chemical attack is monitoring for toxic compounds on surfaces within that facility. Low level detection of toxicant(s) is necessary to ensure that these compounds have been eliminated after building decontaminatio...

  3. DETECTION OF TOXICANT(S) ON BUILDING SURFACES FOLLOWING CHEMICAL ATTACK

    EPA Science Inventory

    A critical step prior to reoccupation of any facility following a chemical attack is monitoring for toxic compounds on surfaces within that facility. Low level detection of toxicant(s) is necessary to ensure that these compounds have been eliminated after building decontaminatio...

  4. Classification of Chemicals Based On Structured Toxicity Information

    EPA Science Inventory

    Thirty years and millions of dollars worth of pesticide registration toxicity studies, historically stored as hardcopy and scanned documents, have been digitized into highly standardized and structured toxicity data within the Toxicity Reference Database (ToxRefDB). Toxicity-bas...

  5. Classification of Chemicals Based On Structured Toxicity Information

    EPA Science Inventory

    Thirty years and millions of dollars worth of pesticide registration toxicity studies, historically stored as hardcopy and scanned documents, have been digitized into highly standardized and structured toxicity data within the Toxicity Reference Database (ToxRefDB). Toxicity-bas...

  6. [Combined biological effect of electromagnetic fields and chemical substances (toxic)].

    PubMed

    Kamedula, M; Kamedula, T

    1996-01-01

    The authors present results of own measurements and examinations as well as the literature data on the occurrence and effect of direct, low and high frequency electromagnetic fields and chemicals. In real working conditions and in experimental conditions, the following relations can be observed: 1) concomitant occurrence of electromagnetic fields and chemicals, e.g. processes of electrolysis, inductive and dielectric heating; 2) experimental studies of combined effect of electromagnetic fields and chemicals on e.g. cancer development: 3) drug effect modified by electromagnetic fields; 4) effect of chemicals produced in materials under the influence of electromagnetic fields. There are only a few publications on medical examinations of workers exposed simultaneously to electromagnetic fields and chemicals. However, even in those reported studies, an attempt to distinguish changes in the health state due to electromagnetic fields, and due to chemicals has field. The studies of the effect of electromagnetic fields which modify the effect of carcinogenic substances have not yielded unequivocal results. Electromagnetic fields may modify significantly the effect of some psychotropic and hormonal drugs. Under the influence of pyrolisis, induced by thermal effect of electromagnetic fields, toxic substances or substances with harmful biological effect may occur in some materials.

  7. Comparison of the radiological and chemical toxicity of lead

    SciTech Connect

    Beitel, G.A.; Mott, S.

    1995-03-01

    This report estimates the worst-case radiological dose to an individual from ingested lead containing picocurie levels of radionuclides and then compares the calculated radiological health effects to the chemical toxic effects from that same lead. This comparison provides an estimate of the consequences of inadvertently recycling, in the commercial market, lead containing nominally undetectable concentrations of radionuclides. Quantitative expressions for the radiological and chemical toxicities of lead are based on concentrations of lead in the blood stream. The result shows that the chemical toxicity of lead is a greater health hazard, by orders of magnitude, than any probable companion radiation dose.

  8. EPA'S TOXCAST PROGRAM FOR PREDICTING HAZARD AND PRIORITIZING TOXICITY TESTING OF ENVIRONMENTAL CHEMICALS

    EPA Science Inventory

    EPA is developing methods for utilizing computational chemistry, high-throughput screening (HTS) and various toxicogenomic technologies to predict potential for toxicity and prioritize limited testing resources towards chemicals that likely represent the greatest hazard to human ...

  9. SIMULATION MODELS FOR ENVIRONMENTAL MULTIMEDIA ANALYSIS OF TOXIC CHEMICALS

    EPA Science Inventory

    Multimedia understanding of pollutant behavior in the environment is of particular concern for chemicals that are toxic and are subject to accumulation in the environmental media (air, soil, water, vegetation) where biota and human exposure is significant. Multimedia simulation ...

  10. SIMULATION MODELS FOR ENVIRONMENTAL MULTIMEDIA ANALYSIS OF TOXIC CHEMICALS

    EPA Science Inventory

    Multimedia understanding of pollutant behavior in the environment is of particular concern for chemicals that are toxic and are subject to accumulation in the environmental media (air, soil, water, vegetation) where biota and human exposure is significant. Multimedia simulation ...

  11. Meta-analysis of toxicity and teratogenicity of 133 chemicals from zebrafish developmental toxicity studies

    EPA Science Inventory

    Zebrafish developmental toxicity testing is an emerging field, which faces considerable challenges regarding data meta-analysis and the establishment of standardized test protocols. Here, we present an initial correlation study on toxicity of 133 chemicals based on data in the li...

  12. SCREENING FOR TOXIC INDUSTRIAL CHEMICALS USING SEMIPERMEABLE MEMBRANE DEVICES WITH RAPID TOXICITY ASSAYS

    EPA Science Inventory

    A time-integrated sampling device interfaced with two toxicity-based assays is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethylsulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

  13. Meta-analysis of toxicity and teratogenicity of 133 chemicals from zebrafish developmental toxicity studies

    EPA Science Inventory

    Zebrafish developmental toxicity testing is an emerging field, which faces considerable challenges regarding data meta-analysis and the establishment of standardized test protocols. Here, we present an initial correlation study on toxicity of 133 chemicals based on data in the li...

  14. SCREENING FOR TOXIC INDUSTRIAL CHEMICALS USING SEMIPERMEABLE MEMBRANE DEVICES WITH RAPID TOXICITY ASSAYS

    EPA Science Inventory

    A time-integrated sampling device interfaced with two toxicity-based assays is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethylsulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

  15. 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: An update.

    PubMed

    Taylor, Katy; Andrew, David J

    2017-09-15

    A previous retrospective analysis of substances in the ECHA CHEM database concluded that, for industrial chemicals with a 'low (sub)acute toxicity profile', further testing in the 90-day study is unlikely to change this profile (Taylor et al., 2014). We have further tested this hypothesis by assessing the outcome of substances with testing proposals for which a prediction was made in that paper that the NOAEL based on the 90-day study would be 1000 mg/kg bw/d. Indeed, for seven out of ten substances for which data was available, the profile was shown to be held. For three substances, the reduced NOAEL was explained by renal effects in the rats, two of which had been seen in the 28-day study but had been dismissed by the study submitter. We conclude that the low toxicity profile will be even more protective if the NOEL is used from the 28-day study and an independent expert view is taken of the human relevance of any effects reported in the 28-day study. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. New TRI data shows chemical industry remains top toxic polluter

    SciTech Connect

    Begley, R.; Rotman, D.

    1993-06-02

    Despite continued declines in emissions, the latest Toxics Release Inventory (TRI) data from the Environmental Protection Agency show the chemical industry was by far the largest emitter of toxic pollutants in 1991. DuPont headed the list of polluting companies, releasing a whopping 243 million lbs of toxic chemical-almost 100 million lbs more than number two Freeport-McMoRan. Releasing 1.55 billion lbs of toxics in 1991, chemical producers are trailed distantly by primary metals at 433 million lbs and paper manufacturing at 242 million lbs. total TRI air releases for all industries declined 13% because of reductions in industrial solvent, chlorine, and ammonia. Water releases rose 24%, primarily because of runoff from four fertilizer plants in Louisiana; and land releases dropped 9% because of decreases in phosphoric acid and metal compounds. The top three states for TRI releases are Lousiana, with 459 million lbs; Texas, with 411 million lbs; and Tennessee, with 215 million lbs.

  17. SIMULATING METABOLISM OF XENOBIOTIC CHEMICALS AS A PREDICTOR OF TOXICITY

    EPA Science Inventory

    EPA is faced with long lists of chemicals that need to be assessed for hazard. A major gap in evaluating chemical risk is accounting for metabolic activation resulting in increased toxicity. The goals of this project are to develop a capability to forecast the metabolism of xenob...

  18. SIMULATING METABOLISM OF XENOBIOTIC CHEMICALS AS A PREDICTOR OF TOXICITY

    EPA Science Inventory

    EPA is faced with long lists of chemicals that need to be assessed for hazard. A major gap in evaluating chemical risk is accounting for metabolic activation resulting in increased toxicity. The goals of this project are to develop a capability to forecast the metabolism of xenob...

  19. EPA'S TOXCAST PROGRAM FOR PREDICTING TOXICITY AND PRIORITIZING ENVIRONMENTAL CHEMICALS

    EPA Science Inventory

    ToxCast is a research program to predict or forecast toxicity by evaluating a broad spectrum of chemicals and effects; physical-chemical properties, predicted bioactivities, HTS and cell-based assays, and genomics. Data will be interpretively linked to known or predicted toxicol...

  20. EPA'S TOXCAST PROGRAM FOR PREDICTING TOXICITY AND PRIORITIZING ENVIRONMENTAL CHEMICALS

    EPA Science Inventory

    ToxCast is a research program to predict or forecast toxicity by evaluating a broad spectrum of chemicals and effects; physical-chemical properties, predicted bioactivities, HTS and cell-based assays, and genomics. Data will be interpretively linked to known or predicted toxicol...

  1. Why toxic equivalency factors are not suitable for perfluoroalkyl chemicals.

    PubMed

    Peters, Jeffrey M; Gonzalez, Frank J

    2011-10-17

    The pervasive nature of perfluoroalkyl chemicals in the environment has generated considerable interest for developing new strategies for risk assessment. In experimental animal models, exposure to perfluoroalkyl chemicals can cause developmental toxicity and hepatotoxicity. Peroxisome proliferator-activated receptor-α (PPARα) is required to mediate some but not all of these effects. Since PPARα has a role in mediating some of these effects, and there is some overlap in the type of toxicities elicited by perfluoroalkyl chemicals, it has been suggested that a scaling system analogous to the toxic equivalency factor (TEF) system used for polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans (PCDF), and polychlorinated biphenyls (PCB) could be used for perfluoroalkyl chemicals. However, evidence suggests that perfluoroalkyl chemicals can activate/interfere with other receptors, and there is reason to suggest the possibility of species differences in the response mediated by different receptors as well as qualitative differences in toxicities elicited by perfluoroalkyl chemicals. These differences and other data gaps preclude the development of a TEF approach for perfluoroalkyl chemicals.

  2. Sediment toxicity in Boston Harbor: Magnitude, extent, and relationships with chemical toxicants. Technical memo

    SciTech Connect

    Long, E.R.; Sloane, G.M.; Carr, R.S.; Scott, K.J.; Thursby, G.B.

    1996-06-01

    A survey of the toxicity of sediments throughout Boston Harbor and vicinity was conducted by NOAA`s National Status and Trends (NS&T) Program. The objectives of the survey were to determine the magnitude and spatial extent of toxicity and the relationship between measures of toxicity and the concentrations of chemical toxicants in the sediments. Multiple toxicity tests were performed including: an amphipod survival test performed with whole sediments, a microbial bioluminescence test performed with organic solvent extracts of the sediments, and sea urchin fertilization and embryological development tests performed with the pore waters extracted from the sediments. Chemical analyses were performed on selected samples for trace metals, polynuclear aromatic hydrcarbons, chlorinated pesticides, PCBs, and butyltins.

  3. The Respiratory Toxicity of Chemical Warefare Agents

    EPA Science Inventory

    Inhalation is one of the most important routes of exposure for chemical warfare agents (CWAs) and thus, the lung remains a critical target of injury. Depending on the mode of action by which the CWAs cause injury, the nature of injury, the location being impacted within the respi...

  4. The Respiratory Toxicity of Chemical Warefare Agents

    EPA Science Inventory

    Inhalation is one of the most important routes of exposure for chemical warfare agents (CWAs) and thus, the lung remains a critical target of injury. Depending on the mode of action by which the CWAs cause injury, the nature of injury, the location being impacted within the respi...

  5. Process safety management for highly hazardous chemicals

    SciTech Connect

    1996-02-01

    Purpose of this document is to assist US DOE contractors who work with threshold quantities of highly hazardous chemicals (HHCs), flammable liquids or gases, or explosives in successfully implementing the requirements of OSHA Rule for Process Safety Management of Highly Hazardous Chemicals (29 CFR 1910.119). Purpose of this rule is to prevent releases of HHCs that have the potential to cause catastrophic fires, explosions, or toxic exposures.

  6. Future of toxicology--predictive toxicology: An expanded view of "chemical toxicity".

    PubMed

    Richard, Ann M

    2006-10-01

    A chemistry approach to predictive toxicology relies on structure-activity relationship (SAR) modeling to predict biological activity from chemical structure. Such approaches have proven capabilities when applied to well-defined toxicity end points or regions of chemical space. These approaches are less well-suited, however, to the challenges of global toxicity prediction, i.e., to predicting the potential toxicity of structurally diverse chemicals across a wide range of end points of regulatory and pharmaceutical concern. New approaches that have the potential to significantly improve capabilities in predictive toxicology are elaborating the "activity" portion of the SAR paradigm. Recent advances in two areas of endeavor are particularly promising. Toxicity data informatics relies on standardized data schema, developed for particular areas of toxicological study, to facilitate data integration and enable relational exploration and mining of data across both historical and new areas of toxicological investigation. Bioassay profiling refers to large-scale high-throughput screening approaches that use chemicals as probes to broadly characterize biological response space, extending the concept of chemical "properties" to the biological activity domain. The effective capture and representation of legacy and new toxicity data into mineable form and the large-scale generation of new bioassay data in relation to chemical toxicity, both employing chemical structure information to inform and integrate diverse biological data, are opening exciting new horizons in predictive toxicology.

  7. An expert system for prediction of chemical toxicity

    USGS Publications Warehouse

    Hickey, James P.; Aldridge, Andrew J.; Passino-Reader, Dora R.; Frank, Anthony M.

    1992-01-01

    The National Fisheries Research Center- Great Lakes has developed an interactive computer program that uses the structure of an organic molecule to predict its acute toxicity to four aquatic species. The expert system software, written in the muLISP language, identifies the skeletal structures and substituent groups of an organic molecule from a user-supplied standard chemical notation known as a SMILES string, and then generates values for four solvatochromic parameters. Multiple regression equations relate these parameters to the toxicities (expressed as log10LC50s and log10EC50s, along with 95% confidence intervals) for four species. The system is demonstrated by prediction of toxicity for anilide-type pesticides to the fathead minnow (Pimephales promelas). This software is designed for use on an IBM-compatible personal computer by personnel with minimal toxicology background for rapid estimation of chemical toxicity. The system has numerous applications, with much potential for use in the pharmaceutical industry

  8. Chemical and radiological toxicity of depleted uranium.

    PubMed

    Sztajnkrycer, Matthew D; Otten, Edward J

    2004-03-01

    A by-product of the uranium enrichment process, depleted uranium (DU) contains approximately 40% of the radioactivity of natural uranium yet retains all of its chemical properties. After its use in the 1991 Gulf War, public concern increased regarding its potential radiotoxicant properties. Whereas in vitro and rodent data have suggested the potential for uranium-induced carcinogenesis, human cohort studies assessing the health effects of natural and DU have failed to validate these findings. Heavy-metal nephrotoxicity has not been noted in either animal studies or Gulf War veteran cohort studies despite markedly elevated urinary uranium excretion. No significant residual environmental contamination has been found in geographical areas exposed to DU. As such, although continued surveillance of exposed cohorts and environments (particularly water sources) are recommended, current data would support the position that DU poses neither a radiological nor chemical threat.

  9. Cumulative risk: toxicity and interactions of physical and chemical stressors.

    PubMed

    Rider, Cynthia V; Boekelheide, Kim; Catlin, Natasha; Gordon, Christopher J; Morata, Thais; Selgrade, Maryjane K; Sexton, Kenneth; Simmons, Jane Ellen

    2014-01-01

    Recent efforts to update cumulative risk assessment procedures to incorporate nonchemical stressors ranging from physical to psychosocial reflect increased interest in consideration of the totality of variables affecting human health and the growing desire to develop community-based risk assessment methods. A key roadblock is the uncertainty as to how nonchemical stressors behave in relationship to chemical stressors. Physical stressors offer a reasonable starting place for measuring the effects of nonchemical stressors and their modulation of chemical effects (and vice versa), as they clearly differ from chemical stressors; and "doses" of many physical stressors are more easily quantifiable than those of psychosocial stressors. There is a commonly held belief that virtually nothing is known about the impact of nonchemical stressors on chemically mediated toxicity or the joint impact of coexposure to chemical and nonchemical stressors. Although this is generally true, there are several instances where a substantial body of evidence exists. A workshop titled "Cumulative Risk: Toxicity and Interactions of Physical and Chemical Stressors" held at the 2013 Society of Toxicology Annual Meeting provided a forum for discussion of research addressing the toxicity of physical stressors and what is known about their interactions with chemical stressors, both in terms of exposure and effects. Physical stressors including sunlight, heat, radiation, infectious disease, and noise were discussed in reference to identifying pathways of interaction with chemical stressors, data gaps, and suggestions for future incorporation into cumulative risk assessments.

  10. Cumulative Risk: Toxicity and Interactions of Physical and Chemical Stressors

    PubMed Central

    Rider, Cynthia V.

    2014-01-01

    Recent efforts to update cumulative risk assessment procedures to incorporate nonchemical stressors ranging from physical to psychosocial reflect increased interest in consideration of the totality of variables affecting human health and the growing desire to develop community-based risk assessment methods. A key roadblock is the uncertainty as to how nonchemical stressors behave in relationship to chemical stressors. Physical stressors offer a reasonable starting place for measuring the effects of nonchemical stressors and their modulation of chemical effects (and vice versa), as they clearly differ from chemical stressors; and “doses” of many physical stressors are more easily quantifiable than those of psychosocial stressors. There is a commonly held belief that virtually nothing is known about the impact of nonchemical stressors on chemically mediated toxicity or the joint impact of coexposure to chemical and nonchemical stressors. Although this is generally true, there are several instances where a substantial body of evidence exists. A workshop titled “Cumulative Risk: Toxicity and Interactions of Physical and Chemical Stressors” held at the 2013 Society of Toxicology Annual Meeting provided a forum for discussion of research addressing the toxicity of physical stressors and what is known about their interactions with chemical stressors, both in terms of exposure and effects. Physical stressors including sunlight, heat, radiation, infectious disease, and noise were discussed in reference to identifying pathways of interaction with chemical stressors, data gaps, and suggestions for future incorporation into cumulative risk assessments. PMID:24154487

  11. Statistical evaluation of chronic toxicity data on aquatic organisms for the hazard identification: the chemicals toxicity distribution approach.

    PubMed

    González-Doncel, Miguel; Ortiz, José; Izquierdo, Juan J; Martín, Bárbara; Sánchez, Paloma; Tarazona, José V

    2006-05-01

    Presently, in the Globally Harmonised System of Classification and Labelling of Chemicals the classification of substances for long-term effects to aquatic life is based on acute toxicity in combination with degradation and/or bioaccumulation potential. Recently an OECD Working Group was created to develop the classification scheme to accommodate chronic toxicity data related to aquatic organisms for assigning a chronic hazard category. This study focuses on a new approach for setting chronic toxicity cut-off values based on Chemicals Toxicity Distributions (CTDs). A CTD is obtained through statistical fitting of the data used by regulatory bodies for setting hazard-based classifications. The CTDs were made using the lowest aquatic NOEC value of each chemical. A review of different toxicological sources reporting acute aquatic toxicities was carried out. Initially, the data were arranged according to the specific source and distributions for key taxonomic groups (i.e. fishes, crustaceans and algae) were evaluated separately. In most cases, no significant departures from normality were observed. Thereafter, a compiled database containing >900 values was developed and the CTDs were constructed for each taxonomic group. Significant deviation from normality (P < 0.05) was observed in the fishes and crustaceans' CTDs. However, this deviation was apparently produced by the presence of only seven values with NOECs <1 x 10(-5) mg l(-1), while high correlation between the data and the normal scores (r-values>or= 0.989) indicated that the data were samples from normal distributions. From these observations, potential cut-off values would allow quantitative estimations of the percentage of chemicals falling into each specific category. This approach results in a simple classification hazard scheme where most chemicals are covered in one of the categories, allowing a clear distribution of the chemicals among three categories for chronic toxicity.

  12. In vitro Cell Culture Model for Toxic Inhaled Chemical Testing

    PubMed Central

    Ahmad, Shama; Ahmad, Aftab; Neeves, Keith B.; Hendry-Hofer, Tara; Loader, Joan E.; White, Carl W.; Veress, Livia

    2014-01-01

    Cell cultures are indispensable to develop and study efficacy of therapeutic agents, prior to their use in animal models. We have the unique ability to model well differentiated human airway epithelium and heart muscle cells. This could be an invaluable tool to study the deleterious effects of toxic inhaled chemicals, such as chlorine, that can normally interact with the cell surfaces, and form various byproducts upon reacting with water, and limiting their effects in submerged cultures. Our model using well differentiated human airway epithelial cell cultures at air-liqiuid interface circumvents this limitation as well as provides an opportunity to evaluate critical mechanisms of toxicity of potential poisonous inhaled chemicals. We describe enhanced loss of membrane integrity, caspase release and death upon toxic inhaled chemical such as chlorine exposure. In this article, we propose methods to model chlorine exposure in mammalian heart and airway epithelial cells in culture and simple tests to evaluate its effect on these cell types. PMID:24837339

  13. In vitro cell culture model for toxic inhaled chemical testing.

    PubMed

    Ahmad, Shama; Ahmad, Aftab; Neeves, Keith B; Hendry-Hofer, Tara; Loader, Joan E; White, Carl W; Veress, Livia

    2014-05-08

    Cell cultures are indispensable to develop and study efficacy of therapeutic agents, prior to their use in animal models. We have the unique ability to model well differentiated human airway epithelium and heart muscle cells. This could be an invaluable tool to study the deleterious effects of toxic inhaled chemicals, such as chlorine, that can normally interact with the cell surfaces, and form various byproducts upon reacting with water, and limiting their effects in submerged cultures. Our model using well differentiated human airway epithelial cell cultures at air-liqiuid interface circumvents this limitation as well as provides an opportunity to evaluate critical mechanisms of toxicity of potential poisonous inhaled chemicals. We describe enhanced loss of membrane integrity, caspase release and death upon toxic inhaled chemical such as chlorine exposure. In this article, we propose methods to model chlorine exposure in mammalian heart and airway epithelial cells in culture and simple tests to evaluate its effect on these cell types.

  14. The subacute inhalation toxicity of 109 industrial chemicals

    PubMed Central

    Gage, J. C.

    1970-01-01

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

  15. Modeling Reproductive Toxicity for Chemical Prioritization into an Integrated Testing Strategy

    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 in over 500 assays of different molecular targets, cellular responses and cell-states. Of th...

  16. EPA's ToxCast Program for Predicting Hazard and Prioritizing the Toxicity Testing of Environmental Chemicals

    EPA Science Inventory

    An alternative is to perform a set of relatively inexpensive and rapid high throughput screening (HTS) assays, derive signatures predictive of effects or modes of chemical toxicity from the HTS data, then use these predictions to prioritize chemicals for more detailed analysis. T...

  17. EPA's ToxCast Program for Predicting Hazard and Prioritizing the Toxicity Testing of Environmental Chemicals

    EPA Science Inventory

    An alternative is to perform a set of relatively inexpensive and rapid high throughput screening (HTS) assays, derive signatures predictive of effects or modes of chemical toxicity from the HTS data, then use these predictions to prioritize chemicals for more detailed analysis. T...

  18. Modeling Reproductive Toxicity for Chemical Prioritization into an Integrated Testing Strategy

    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 in over 500 assays of different molecular targets, cellular responses and cell-states. Of th...

  19. Development of a Daphnia magna DNA microarray for evaluating the toxicity of environmental chemicals.

    PubMed

    Watanabe, Hajime; Takahashi, Eri; Nakamura, Yuko; Oda, Shigeto; Tatarazako, Norihisa; Iguchi, Taisen

    2007-04-01

    Toxic chemical contaminants have a variety of detrimental effects on various species, and the impact of pollutants on ecosystems has become an urgent issue. However, the majority of studies regarding the effects of chemical contaminants have focused on vertebrates. Among aquatic organisms, Daphnia magna has been used extensively to evaluate organism- and population-level responses of invertebrates to pollutants in acute toxicity or reproductive toxicity tests. Although these types of tests can provide information concerning hazardous concentrations of chemicals, they provide no information about their mode of action. Recent advances in molecular genetic techniques have provided tools to better understand the responses of aquatic organisms to pollutants. In the present study, we adapted some of the techniques of molecular genetics to develop new tools, which form the basis for an ecotoxicogenomic assessment of D. magna. Based on a Daphnia expressed sequence tag database, we developed an oligonucleotide-based DNA microarray with high reproducibility. The DNA microarray was used to evaluate gene expression profiles of neonatal daphnids exposed to several different chemicals: Copper sulfate, hydrogen peroxide, pentachlorophenol, or beta-naphthoflavone. Exposure to these chemicals resulted in characteristic patterns of gene expression that were chemical-specific, indicating that the Daphnia DNA microarray can be used for classification of toxic chemicals and for development of a mechanistic understanding of chemical toxicity on a common freshwater organism.

  20. Effects of toxic metals and chemicals on biofilm and biocorrosion.

    PubMed

    Fang, Herbert H P; Xu, Li-Chong; Chan, Kwong-Yu

    2002-11-01

    Microbes in marine biofilms aggregated into clusters and increased the production of extracellular polymeric substances (EPS), by over 100% in some cases, when the seawater media containing toxic metals and chemicals, such as Cd(II), Cu(II), Pb(II), Zn(II), AI(III), Cr(III), glutaraldehyde, and phenol. The formation of microbial cluster and the increased production of EPS, which contained 84-92% proteins and 8-16% polysaccharides, accelerated the corrosion of the mild steel. However, there was no quantitative relationship between the degree of increased corrosion and the toxicity of metals/chemicals towards sulfate-reducing bacteria, or the increased EPS production.

  1. A DNA-based assay for toxic chemicals in wastewater.

    PubMed

    Foreman, Amy L; Phillips, Leo; Kanellis, Vangelis G; Hammoudeh, Daoud; Naumann, Christoph; Wong, Henri; Chisari, Robert; Hibbert, D Brynn; Lee, Garry S H; Patra, Ronald; Julli, Moreno; Chapman, John; Cooke, A Roger; dos Remedios, Cristobal G

    2011-08-01

    Chemical toxicants, particularly metal ions, are a major contaminant in global waterways. Live-organism bioassays used to monitor chemical toxicants commonly involve measurements of activity or survival of a freshwater cladoceran (Ceriodaphnia dubia) or light emitted by the marine bacterium Vibrio fischeri, used in the commercial Microtox® bioassay. Here we describe a novel molecule-based assay system employing DNA as the chemical biosensor. Metals bind to DNA, causing structural changes that expel a bound (intercalated) fluorescent reporter dye. Analyses of test data using 48 wastewater samples potentially contaminated by metal ions show that the DNA-dye assay results correlate with those from C. dubia and Microtox bioassays. All three assays exhibit additive, antagonistic, and synergistic responses that cannot be predicted by knowing individual metal concentrations. Analyses of metals in these samples imply the presence of chemical toxicants other than metal ions. The DNA-dye assay is robust, has a 12-month shelf life, and is only slightly affected by sample pH in the range 4 to 9. The assay is completed in a matter of minutes, and its portability makes it well suited as a screening assay for use in the field. We conclude that the DNA-dye test is a surrogate bioassay suitable for screening chemical toxicity.

  2. In vitro screening for population variability in chemical toxicity.

    PubMed

    O'Shea, Shannon H; Schwarz, John; Kosyk, Oksana; Ross, Pamela K; Ha, Min Jin; Wright, Fred A; Rusyn, Ivan

    2011-02-01

    Immortalized human lymphoblastoid cell lines have been used to demonstrate that it is possible to use an in vitro model system to identify genetic factors that affect responses to xenobiotics. To extend the application of such studies to investigative toxicology by assessing interindividual and population-wide variability and heritability of chemical-induced toxicity phenotypes, we have used cell lines from the Centre d'Etude du Polymorphisme Humain (CEPH) trios assembled by the HapMap Consortium. Our goal is to aid in the development of predictive in vitro genetics-anchored models of chemical-induced toxicity. Cell lines from the CEPH trios were exposed to three concentrations of 14 environmental chemicals. We assessed ATP production and caspase-3/7 activity 24 h after treatment. Replicate analyses were used to evaluate experimental variability and classify responses. We show that variability of response across the cell lines exists for some, but not all, chemicals, with perfluorooctanoic acid (PFOA) and phenobarbital eliciting the greatest degree of interindividual variability. Although the data for the chemicals used here do not show evidence for broad-sense heritability of toxicity response phenotypes, substantial cell line variation was found, and candidate genetic factors contributing to the variability in response to PFOA were investigated using genome-wide association analysis. The approach of screening chemicals for toxicity in a genetically defined yet diverse in vitro human cell-based system is potentially useful for identification of chemicals that may pose a highest risk, the extent of within-species variability in the population, and genetic loci of interest that potentially contribute to chemical susceptibility.

  3. Chemical toxicity correlations for several fish species based on the Abraham solvation parameter model.

    PubMed

    Hoover, Kaci R; Acree, William E; Abraham, Michael H

    2005-09-01

    The Abraham solvation parameter model is used to construct mathematical correlations for describing the nonspecific aquatic toxicity of organic compounds to the fathead minnow, guppy, bluegill, goldfish, golden orfe, and high-eyes medaka. The derived mathematical correlations describe the observed published toxicity data to within an overall average standard deviation of approximately 0.28 log units. In the case of ester solutes, the descriptions were improved by introducing an indicator variable into the basic model. Derived correlations can be used to estimate aquatic toxicities of organic chemicals to the six fish species studied and to help in identifying compounds whose toxic mode of action might involve chemical specific reactivity, rather than nonpolar or polar narcosis. A principal component analysis of the correlation equations shows that the water-octanol system is a poor model for nonspecific aquatic toxicity but that the water-isobutanol and water-pentanol systems are much better models.

  4. A review of the toxicity of chemical dispersants.

    PubMed

    Wise, James; Wise, John Pierce

    2011-01-01

    Chemical dispersants are a mixture of various surfactants and solvents. Most dispersants are proprietary, and the complete composition is not often public knowledge. Chemical dispersants used for the cleanup and containment of crude oil toxicity became a major concern after the 2010 Deepwater Horizon oil crisis in the Gulf of Mexico. During the crisis, millions of liters of chemical dispersants (Corexit 9527 and 9500) were used--the largest known application of dispersants in the field. As of February 2011, 38 peer-reviewed articles were available on the toxicity of 35 different chemical dispersants. Nalco, BP, Shell, and Total Special Fluids manufacture a variety of chemical dispersants. Most notably, Nalco manufactures Corexit 9527 and 9500, and 19 miscellaneous dispersants are manufactured by others. Most studies examined the lethality of the dispersants. Several nonlethal end points were considered, including the effect on predator/prey recognition, enzyme activity changes, effects on hatchability, and the threshold for bradycardia. The animals studied included Daphnia (small planktonic crustaceans), anemones, corals, crustaceans, starfish, mollusks, fish, birds, and rats. Studies in birds and mammals are distinctly lacking. The variety of chemical dispersants, the variability in test methods, and the lack of distinct species overlap between studies make it difficult to compare and deduce which dispersant is most toxic and which is least. Here, we offer some attempt at comparing Corexit 9527 and 9500 (because these have had the largest field application), but significantly more research is needed before clear conclusions can be drawn.

  5. Acute mixture toxicity of halogenated chemicals and their next generation counterparts on zebrafish embryos.

    PubMed

    Godfrey, Amy; Abdel-Moneim, Ahmed; Sepúlveda, Maria S

    2017-08-01

    Perfluorinated chemicals and flame retardants are halogenated compounds commonly used in food packaging and in clothing and electronics, respectively. Due to the hazardous effects of many of these chemicals, manufacturers are developing next generation potential less toxic alternatives. The objective of this study was to assess the toxicity of potentially "safer" alternatives, singly and in mixtures, in relation to their first generation counterparts. We used zebrafish embryos as our model organism due to its high structural and functional homology to other vertebrates and its suitability for early developmental studies. We tested three well studied halogens, perfluorooctanoic acid (PFOA), tris (1,3-dichloro-2-propyl) phosphate (TDCPP) and tetrabromobisphenal A (TBBPA), and two less-studied next generation chemicals, 9,10-Dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO) and perfluorobutyric acid (PFBA). First, we identified their lethal concentration (LC50) under 96 h exposures using zebrafish embryos; chemical LC50 values ranged from 1.3 to 13,795 ppm. Next, we tested the toxicity of tertiary mixtures containing the estimated LC50 values for each chemical which ranged from 126 to 5,094 ppm. We found that chemicals within these mixtures displayed concentration addition suggesting a similar mode of toxic action. Importantly, next generation chemicals were less acutely toxic singly and in mixtures than their first generation counterpart. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Relevancy in Basic Courses: Considering Toxic Chemical Disposal.

    ERIC Educational Resources Information Center

    Sollimo, Vincent J.

    1985-01-01

    A 2-week unit on toxic chemical waste disposal is used in a physical science course for nonscience majors. Descriptions of the unit, supplementary student activities, and student library project are provided. Also provided are selected student responses to a five-question survey on the unit. (JN)

  7. Toxicity of fishery chemicals to the asiatic clam, Corbicula manilensis

    USGS Publications Warehouse

    Chandler, Jack H.; Marking, L.L.

    1979-01-01

    The Asiatic clam (Corbicula manilensis), a species introduced into U. S. waters, has spread rapidly, and its ability to survive, reproduce, and spread has caused concern. Aquatic biologists suspect that the clams may crowd out indigenous mollusks, and the animals sometimes plug water intakes and leave shell deposits that interfere with sand and gravel operations. The toxicity of 20 commonly used fishery chemicals to the Asiatic clam was determined to evaluate hazards to a nontarget aquatic invertebrate and to assess the potential of the chemicals for controlling clam populations. Among six piscicides and two lampricides tested, antimycin was most toxic to the clam; the 96-h LC50 was 0.065 mg/L. Among three therapeutants and two disinfectants tested, nifurpirinol was the most toxic; the 96-h LC50 was 7.60 mg/L. All of the compounds were less toxic to the clam than to fish. As a nontarget organism, this clam would be safe in water treated with any of the tested fishery chemicals at recommended use pattern concentrations. None of the chemicals have potential for controlling unwanted populations of these clams.

  8. Yellow phosphorus process to convert toxic chemicals to non-toxic products

    DOEpatents

    Chang, S.G.

    1994-07-26

    The present invention relates to a process for generating reactive species for destroying toxic chemicals. This process first contacts air or oxygen with aqueous emulsions of molten yellow phosphorus. This contact results in rapid production of abundant reactive species such as O, O[sub 3], PO, PO[sub 2], etc. A gaseous or liquid aqueous solution organic or inorganic chemicals is next contacted by these reactive species to reduce the concentration of toxic chemical and result in a non-toxic product. The final oxidation product of yellow phosphorus is phosphoric acid of a quality which can be recovered for commercial use. A process is developed such that the byproduct, phosphoric acid, is obtained without contamination of toxic species in liquids treated. A gas stream containing ozone without contamination of phosphorus containing species is also obtained in a simple and cost-effective manner. This process is demonstrated to be effective for destroying many types of toxic organic, or inorganic, compounds, including polychlorinated biphenyls (PCB), aromatic chlorides, amines, alcohols, acids, nitro aromatics, aliphatic chlorides, polynuclear aromatic compounds (PAH), dyes, pesticides, sulfides, hydroxyamines, ureas, dithionates and the like. 20 figs.

  9. Yellow phosphorus process to convert toxic chemicals to non-toxic products

    DOEpatents

    Chang, Shih-Ger

    1994-01-01

    The present invention relates to a process for generating reactive species for destroying toxic chemicals. This process first contacts air or oxygen with aqueous emulsions of molten yellow phosphorus. This contact results in rapid production of abundant reactive species such as O, O.sub.3, PO, PO.sub.2, etc. A gaseous or liquid aqueous solution organic or inorganic chemicals is next contacted by these reactive species to reduce the concentration of toxic chemical and result in a non-toxic product. The final oxidation product of yellow phosphorus is phosphoric acid of a quality which can be recovered for commercial use. A process is developed such that the byproduct, phosphoric acid, is obtained without contamination of toxic species in liquids treated. A gas stream containing ozone without contamination of phosphorus containing species is also obtained in a simple and cost-effective manner. This process is demonstrated to be effective for destroying many types of toxic organic, or inorganic, compounds, including polychlorinated biphenyls (PCB), aromatic chlorides, amines, alcohols, acids, nitro aromatics, aliphatic chlorides, polynuclear aromatic compounds (PAH), dyes, pesticides, sulfides, hydroxyamines, ureas, dithionates and the like.

  10. Designing ionic liquids: the chemical structure role in the toxicity.

    PubMed

    Ventura, Sónia P M; Gonçalves, Ana M M; Sintra, Tânia; Pereira, Joana L; Gonçalves, Fernando; Coutinho, João A P

    2013-01-01

    Ionic liquids (ILs) are a novel class of solvents with interesting physicochemical properties. Many different applications have been reported for ILs as alternatives to organic solvents in chemical and bioprocesses. Despite the argued advantage of having low vapor pressure, even the most hydrophobic ILs show some degree of solubility in water, allowing their dispersion into aquatic systems and raising concerns on its pollutant potential. Moreover, nowadays most widespread notion concerning the ILs toxicity is that there is a direct relationship with their hydrophobicity/lipophilicity. This work aims at enlarging the currently limited knowledge on ILs toxicity by addressing negative impacts in aquatic ecosystems and investigating the possibility of designing hydrophobic ILs of low ecotoxicity, by the manipulation of their chemical structures. The impact of aromaticity on the toxicity of different cations (pyridinium, piperidinium, pyrrolidinium and imidazolium) and hydrophobic anions (bis(trifluoromethylsulfonyl)imide [NTf(2)] and hexafluorophosphate [PF(6)]) was analysed. Concomitantly, several imidazolium-based ILs of the type [C( n )C( m )C( j )im][NTf(2)] were also studied to evaluate the effects of the position of the alkyl chain on the ILs' toxicity. For that purpose, standard assays were performed using organisms of different trophic levels, Vibrio fischeri, Pseudokirchneriella subcapitata and Daphnia magna, allowing to evaluate the consistency of the structure-activity relationships across different biological targets. The results here reported suggest the possibility of designing ILs with an enhanced hydrophobic character and lower toxicity, by elimination of their aromatic nature.

  11. An in silico algal toxicity model with a wide applicability potential for industrial chemicals and pharmaceuticals.

    PubMed

    Önlü, Serli; Saçan, Melek Türker

    2017-04-01

    The authors modeled the 72-h algal toxicity data of hundreds of chemicals with different modes of action as a function of chemical structures. They developed mode of action-based local quantitative structure-toxicity relationship (QSTR) models for nonpolar and polar narcotics as well as a global QSTR model with a wide applicability potential for industrial chemicals and pharmaceuticals. The present study rigorously evaluated the generated models, meeting the Organisation for Economic Co-operation and Development principles of robustness, validity, and transparency. The proposed global model had a broad structural coverage for the toxicity prediction of diverse chemicals (some of which are high-production volume chemicals) with no experimental toxicity data. The global model is potentially useful for endpoint predictions, the evaluation of algal toxicity screening, and the prioritization of chemicals, as well as for the decision of further testing and the development of risk-management measures in a scientific and regulatory frame. Environ Toxicol Chem 2017;36:1012-1019. © 2016 SETAC. © 2016 SETAC.

  12. Molecular Mechanisms of Aldehyde Toxicity: A Chemical Perspective

    PubMed Central

    2015-01-01

    Aldehydes are electrophilic compounds to which humans are pervasively exposed. Despite a significant health risk due to exposure, the mechanisms of aldehyde toxicity are poorly understood. This ambiguity is likely due to the structural diversity of aldehyde derivatives and corresponding differences in chemical reactions and biological targets. To gain mechanistic insight, we have used parameters based on the hard and soft, acids and bases (HSAB) theory to profile the different aldehyde subclasses with respect to electronic character (softness, hardness), electrophilic reactivity (electrophilic index), and biological nucleophilic targets. Our analyses indicate that short chain aldehydes and longer chain saturated alkanals are hard electrophiles that cause toxicity by forming adducts with hard biological nucleophiles, e.g., primary nitrogen groups on lysine residues. In contrast, α,β-unsaturated carbonyl derivatives, alkenals, and the α-oxoaldehydes are soft electrophiles that preferentially react with soft nucleophilic thiolate groups on cysteine residues. The aldehydes can therefore be grouped into subclasses according to common electronic characteristics (softness/hardness) and molecular mechanisms of toxicity. As we will discuss, the toxic potencies of these subgroups are generally related to corresponding electrophilicities. For some aldehydes, however, predictions of toxicity based on electrophilicity are less accurate due to inherent physicochemical variables that limit target accessibility, e.g., steric hindrance and solubility. The unsaturated aldehydes are also members of the conjugated type-2 alkene chemical class that includes α,β-unsaturated amide, ketone, and ester derivatives. Type-2 alkenes are electrophiles of varying softness and electrophilicity that share a common mechanism of toxicity. Therefore, exposure to an environmental mixture of unsaturated carbonyl derivatives could cause “type-2 alkene toxicity” through additive interactions

  13. New High Throughput Methods to Estimate Chemical ...

    EPA Pesticide Factsheets

    EPA has made many recent advances in high throughput bioactivity testing. However, concurrent advances in rapid, quantitative prediction of human and ecological exposures have been lacking, despite the clear importance of both measures for a risk-based approach to prioritizing and screening chemicals. A recent report by the National Research Council of the National Academies, Exposure Science in the 21st Century: A Vision and a Strategy (NRC 2012) laid out a number of applications in chemical evaluation of both toxicity and risk in critical need of quantitative exposure predictions, including screening and prioritization of chemicals for targeted toxicity testing, focused exposure assessments or monitoring studies, and quantification of population vulnerability. Despite these significant needs, for the majority of chemicals (e.g. non-pesticide environmental compounds) there are no or limited estimates of exposure. For example, exposure estimates exist for only 7% of the ToxCast Phase II chemical list. In addition, the data required for generating exposure estimates for large numbers of chemicals is severely lacking (Egeghy et al. 2012). This SAP reviewed the use of EPA's ExpoCast model to rapidly estimate potential chemical exposures for prioritization and screening purposes. The focus was on bounded chemical exposure values for people and the environment for the Endocrine Disruptor Screening Program (EDSP) Universe of Chemicals. In addition to exposure, the SAP

  14. New High Throughput Methods to Estimate Chemical ...

    EPA Pesticide Factsheets

    EPA has made many recent advances in high throughput bioactivity testing. However, concurrent advances in rapid, quantitative prediction of human and ecological exposures have been lacking, despite the clear importance of both measures for a risk-based approach to prioritizing and screening chemicals. A recent report by the National Research Council of the National Academies, Exposure Science in the 21st Century: A Vision and a Strategy (NRC 2012) laid out a number of applications in chemical evaluation of both toxicity and risk in critical need of quantitative exposure predictions, including screening and prioritization of chemicals for targeted toxicity testing, focused exposure assessments or monitoring studies, and quantification of population vulnerability. Despite these significant needs, for the majority of chemicals (e.g. non-pesticide environmental compounds) there are no or limited estimates of exposure. For example, exposure estimates exist for only 7% of the ToxCast Phase II chemical list. In addition, the data required for generating exposure estimates for large numbers of chemicals is severely lacking (Egeghy et al. 2012). This SAP reviewed the use of EPA's ExpoCast model to rapidly estimate potential chemical exposures for prioritization and screening purposes. The focus was on bounded chemical exposure values for people and the environment for the Endocrine Disruptor Screening Program (EDSP) Universe of Chemicals. In addition to exposure, the SAP

  15. Toxic neuropathies: Mechanistic insights based on a chemical perspective.

    PubMed

    LoPachin, Richard M; Gavin, Terrence

    2015-06-02

    2,5-Hexanedione (HD) and acrylamide (ACR) are considered to be prototypical among chemical toxicants that cause central-peripheral axonopathies characterized by distal axon swelling and degeneration. Because the demise of distal regions was assumed to be causally related to the onset of neurotoxicity, substantial effort was devoted to deciphering the respective mechanisms. Continued research, however, revealed that expression of the presumed hallmark morphological features was dependent upon the daily rate of toxicant exposure. Indeed, many studies reported that the corresponding axonopathic changes were late developing effects that occurred independent of behavioral and/or functional neurotoxicity. This suggested that the toxic axonopathy classification might be based on epiphenomena related to dose-rate. Therefore, the goal of this mini-review is to discuss how quantitative morphometric analyses and the establishment of dose-dependent relationships helped distinguish primary, mechanistically relevant toxicant effects from non-specific consequences. Perhaps more importantly, we will discuss how knowledge of neurotoxicant chemical nature can guide molecular-level research toward a better, more rational understanding of mechanism. Our discussion will focus on HD, the neurotoxic γ-diketone metabolite of the industrial solvents n-hexane and methyl-n-butyl ketone. Early investigations suggested that HD caused giant neurofilamentous axonal swellings and eventual degeneration in CNS and PNS. However, as our review will point out, this interpretation underwent several iterations as the understanding of γ-diketone chemistry improved and more quantitative experimental approaches were implemented. The chemical concepts and design strategies discussed in this mini-review are broadly applicable to the mechanistic studies of other chemicals (e.g., n-propyl bromine, methyl methacrylate) that cause toxic neuropathies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Toxic Neuropathies: Mechanistic Insights Based On A Chemical Perspective

    PubMed Central

    LoPachin, Richard M.; Gavin, Terrence

    2014-01-01

    2,5-Hexanedione (HD) and acrylamide (ACR) are considered to be prototypical among chemical toxicants that cause central-peripheral axonopathies characterized by distal axon swelling and degeneration. Because the demise of distal regions was assumed to be causally related to the onset of neurotoxicity, substantial effort was devoted to deciphering the respective mechanisms. Continued research, however, revealed that expression of the presumed hallmark morphological features was dependent upon the daily rate of toxicant exposure. Indeed, many studies reported that the corresponding axonopathic changes were late developing effects that occurred independent of behavioral and/or functional neurotoxicity. This suggested that the toxic axonopathy classification might be based on epiphenomena related to dose-rate. Therefore, the goal of this mini-review is to discuss how quantitative morphometric analyses and the establishment of dose-dependent relationships helped distinguish primary, mechanistically relevant toxicant effects from non-specific consequences. Perhaps more importantly, we will discuss how knowledge of neurotoxicant chemical nature can guide molecular-level research toward a better, more rational understanding of mechanism. Our discussion will focus on HD, the neurotoxic γ-diketone metabolite of the industrial solvents n-hexane and methyl-n-butyl ketone. Early investigations suggested that HD caused giant neurofilamentous axonal swellings and eventual degeneration in CNS and PNS. However, as our review will point out, this interpretation underwent several iterations as the understanding of γ-diketone chemistry improved and more quantitative experimental approaches were implemented. The chemical concepts and design strategies discussed in this mini-review are broadly applicable to the mechanistic studies of other chemicals (e.g., n-propyl bromine, methyl methacrylate) that cause toxic neuropathies. PMID:25218479

  17. Spatial Variability in Toxicity Indicators Used to Rank Chemical Risks

    PubMed Central

    Cutter, Susan L.; Scott, Michael S.; Hill, Arleen A.

    2002-01-01

    Objectives. This study used 6 different measures of toxicity to explore spatial and statistical variations in relative risk indicators of Toxic Release Inventory emissions. Methods. Statistical and spatial correlations between the 6 indices were computed for individual South Carolina facilities. Results. Although the 6 toxicity indices are not highly correlated in theory, they have more commonality in practice. There was significant spatial variation in the indices by individual facility level. Conclusions. Environmental justice researchers must be cognizant of differences in toxicity indices because the choice of the toxicity measure can alter (statistically and spatially) the results of equity analyses and lead to erroneous conclusions. (Am J Public Health. 2002;92:420-422) PMID:11867323

  18. 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 ...

  19. 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...

  20. 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...

  1. 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 ...

  2. Identifying and designing chemicals with minimal acute aquatic toxicity.

    PubMed

    Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T; Zimmerman, Julie Beth

    2015-05-19

    Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure-activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical-chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard.

  3. Identifying and designing chemicals with minimal acute aquatic toxicity

    PubMed Central

    Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T.; Zimmerman, Julie Beth

    2015-01-01

    Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure–activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical–chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard. PMID:24639521

  4. Toxicity assessment of unintentional exposure to multiple chemicals

    SciTech Connect

    Mumtaz, M.M. Ruiz, P.; De Rosa, C.T.

    2007-09-01

    Typically exposure to environmental chemicals is unintentional, and often the exposure is to chemical mixtures, either simultaneously or sequentially. When exposure occurs, in public health practice, it is prudent to ascertain if thresholds for harmful health effects are exceeded, whether by individual chemicals or by chemicals in combination. Three alternative approaches are available for assessing the toxicity of chemical mixtures. Each approach, however, has shortcomings. As the procedures of each approach are described in this paper, at various steps research needs are identified. Recently, reliance has increased on computational toxicology methods for predicting toxicological effects when data are limited. Advances in molecular biology, identification of biomarkers, and availability of accurate and sensitive methods allow us to more precisely define the relationships between multiple chemical exposures and health effects, both qualitatively and quantitatively. Key research needs are best fulfilled through collaborative research. It is through such collaborations that resources are most effectively leveraged to further develop and apply toxicity assessment methods that advance public health practices in vulnerable communities.

  5. Cobalt toxicity: chemical and radiological combined effects on HaCaT keratinocyte cell line.

    PubMed

    Gault, N; Sandre, C; Poncy, J-L; Moulin, C; Lefaix, J-L; Bresson, C

    2010-02-01

    Cobalt (Co) is an essential trace element well known as a constituent of vitamin B(12), but different compounds of Co are also described as highly toxic and/or radiotoxic for individuals or the environment. In nuclear power plants, (58)Co and (60)Co are radioactive isotopes of cobalt present as activation products of stable Co and Ni used in alloys. Skin exposure is a current occupational risk in the hard metal and nuclear industries. As biochemical and molecular cobalt-induced toxicological mechanisms are not fully identified, we investigated cobalt toxicity in a model human keratinocyte cell line, HaCaT. In this study, we propose a model to determine the in vitro chemical impact on cell viability of a soluble form of cobalt (CoCl(2)) with or without gamma-ray doses to mimic contamination by (60)Co, to elucidate the mechanisms of cobalt intracellular chemical and radiological toxicity. Intracellular cobalt concentration was determined after HaCaT cell contamination and chemical toxicity was evaluated in terms of cellular viability and clonogenic survival. We investigated damage to DNA in HaCaT cells by combined treatment with chemical cobalt and a moderate gamma-ray dose. Additive effects of cobalt and irradiation were demonstrated. The underlying mechanism of cobalt toxicity is not clearly established, but our results seem to indicate that the toxicity of Co(II) and of irradiation arises from production of reactive oxygen species.

  6. Exploring the role of quantum chemical descriptors in modeling acute toxicity of diverse chemicals to Daphnia magna.

    PubMed

    Reenu; Vikas

    2015-09-01

    Various quantum-mechanically computed molecular and thermodynamic descriptors along with physico-chemical, electrostatic and topological descriptors are compared while developing quantitative structure-activity relationships (QSARs) for the acute toxicity of 252 diverse organic chemicals towards Daphnia magna. QSAR models based on the quantum-chemical descriptors, computed with routinely employed advanced semi-empirical and ab-initio methods, along with the electron-correlation contribution (CORR) of the descriptors, are analyzed for the external predictivity of the acute toxicity. The models with reliable internal stability and external predictivity are found to be based on the HOMO energy along with the physico-chemical, electrostatic and topological descriptors. Besides this, the total energy and electron-correlation energy are also observed as highly reliable descriptors, suggesting that the intra-molecular interactions between the electrons play an important role in the origin of the acute toxicity, which is in fact an unexplored phenomenon. The models based on quantum-chemical descriptors such as chemical hardness, absolute electronegativity, standard Gibbs free energy and enthalpy are also observed to be reliable. A comparison of the robust models based on the quantum-chemical descriptors computed with various quantum-mechanical methods suggests that the advanced semi-empirical methods such as PM7 can be more reliable than the ab-initio methods which are computationally more expensive. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Guidelines for developmental toxicity testing of chemicals in Japan

    SciTech Connect

    Tanimura, T.

    1985-11-01

    With the definition of teratogenicity expanded in terms of the developmental stages when an agent acts and the types of developmental anomalies induced, the concept of developmental toxicity has been established. The examination of functional developmental disorders including behavior has become one of the most important items for the evaluation of developmental toxicity of chemicals, especially pharmaceutical drugs. The guidelines for developmental toxicity testing of drugs in Japan stress the need for examination of growth and development including behavior and fertility on the postweaning offspring. The outline of the Japanese guidelines is presented and it is emphasized that studies should be done as research and include self evaluation of the scientific truth of the experiment and extrapolation to humans. In addition, the activities of the Behavioral Teratology Meeting, a satellite meeting to the Japanese Teratology Society, are introduced and enquete surveys of the Japan Pharmaceutical Manufacturers Association and collaborative studies for the standardization of learning tests in Japan are briefly presented.

  8. Metal-organic frameworks for the removal of toxic industrial chemicals and chemical warfare agents.

    PubMed

    Bobbitt, N Scott; Mendonca, Matthew L; Howarth, Ashlee J; Islamoglu, Timur; Hupp, Joseph T; Farha, Omar K; Snurr, Randall Q

    2017-06-06

    Owing to the vast diversity of linkers, nodes, and topologies, metal-organic frameworks can be tailored for specific tasks, such as chemical separations or catalysis. Accordingly, these materials have attracted significant interest for capture and/or detoxification of toxic industrial chemicals and chemical warfare agents. In this paper, we review recent experimental and computational work pertaining to the capture of several industrially-relevant toxic chemicals, including NH3, SO2, NO2, H2S, and some volatile organic compounds, with particular emphasis on the challenging issue of designing materials that selectively adsorb these chemicals in the presence of water. We also examine recent research on the capture and catalytic degradation of chemical warfare agents such as sarin and sulfur mustard using metal-organic frameworks.

  9. [Influence of specification on chemical composition of dissolution and hepatocytes toxicity of Polygonum multiflorum].

    PubMed

    lI, Yu-Meng; Li, Rui-Yu; Niu, Ming; Li, Chun-Yu; Bai, Zhao-Fang; Feng, Wu-Wen; Zhang, Cong-En; Tan, Peng; Huang, Zhi-Pu; Ma, Wei-Guang; Wang, Jia-Bo; Xiao, Xiao-He

    2016-03-01

    According to different toxicities of various aqueous extracts of Polygonum multiflorum on hepatocyte, the impacts of chemical composition on the safety of P. multiforum was studied. In this study, 8 main chemical compositions in aqueous extracts of P. multiflorum were determined by the established HPLC method; at the same time, the inhibition ratios of different aqueous extracts of P. multiflorum on L02 cell were determined. Afterwards, the potential compounds related to the toxicity of P. multiforum were tentatively found through a multiple correlation analysis. The results showed that P. multiforum with different chemical compositions exhibited great differences in dissolution. The hepatocyte toxicity of P. multiflorum powder was much greater than P. multiflorum lumps. In addition, three constituents closely related to toxicity of P. multiflorum were found by multiple correlation analysis. The study revealed that chemical composition of P. multiflorum is closely related to the hepatotoxicity, and the hepatotoxicity of P. multiflorum powder is greater than that of other dosage forms. This study indicates that P. multiflorum with different chemical compositions show varying toxicity, which therefore shall be given high attention. Copyright© by the Chinese Pharmaceutical Association.

  10. Toxic hazard and chemical analysis of leachates from furfurylated wood.

    PubMed

    Pilgård, Annica; Treu, Andreas; van Zeeland, Albert N T; Gosselink, Richard J A; Westin, Mats

    2010-09-01

    The furfurylation process is an extensively investigated wood modification process. Furfuryl alcohol molecules penetrate into the wood cell wall and polymerize in situ. This results in a permanent swelling of the wood cell walls. It is unclear whether or not chemical bonds exist between the furfuryl alcohol polymer and the wood. In the present study, five different wood species were used, both hardwoods and softwoods. They were treated with three different furfurylation procedures and leached according to three different leaching methods. The present study shows that, in general, the leachates from furfurylated wood have low toxicity. It also shows that the choice of leaching method is decisive for the outcome of the toxicity results. Earlier studies have shown that leachates from wood treated with furfuryl alcohol prepolymers have higher toxicity to Vibrio fischeri than leachates from wood treated with furfuryl alcohol monomers. This is probably attributable to differences in leaching of chemical compounds. The present study shows that this difference in the toxicity most likely cannot be attributed to maleic acid, furan, furfural, furfuryl alcohol, or 2-furoic acid. However, the difference might be caused by the two substances 5-hydroxymethylfurfural and 2,5-furandimethanol. The present study found no difference in the amount of leached furfuryl alcohol between leachates from furfurylated softwood and furfurylated hardwood species. Earlier studies have indicated differences in grafting of furfuryl alcohol to lignin. However, nothing was found in the present study that could support this. The leachates of furfurylated wood still need to be

  11. Applying mechanisms of chemical toxicity to predict drug safety.

    PubMed

    Guengerich, F Peter; MacDonald, James S

    2007-03-01

    Toxicology can no longer be used only as a science that reacts to problems but must be more proactive in predicting potential human safety issues with new drug candidates. Success in this area must be based on an understanding of the mechanisms of toxicity. This review summarizes and extends some of the concepts of an American Chemical Society ProSpectives meeting on the title subject held in June 2006. One important area is the discernment of the exact nature of the most common problems in drug toxicity. Knowledge of chemical structure alerts and relevant biological pathways are important. Biological activation to reactive products and off-target pharmacology are considered to be major contexts of drug toxicity, although defining exactly what the contributions are is not trivial. Some newer approaches to screening for both have been developed. A goal in predictive toxicology is the use of in vitro methods and database development to make predictions concerning potential modes of toxicity and to stratify drug candidates for further development. Such predictions are desirable for several economic and other reasons but are certainly not routine yet. However, progress has been made using several approaches. Some examples of the application of studies of wide-scale biological responses are now available, with incorporation into development paradigms.

  12. For Debate: Impotence in Farm Workers using Toxic Chemicals

    PubMed Central

    Espir, Michael L. E.; Hall, J. W.; Shirreffs, J. G.; Stevens, David L.

    1970-01-01

    Four out of five members of a team of farmworkers who had been using various herbicides and pesticides in intensive agriculture became impotent. Sexual function recovered after further contact with the chemicals was stopped and hormone therapy had been given, though in one case this took about a year. We have not been able to incriminate one particular substance, but with the circumstantial evidence and the lack of any other obvious cause it seems likely that the impotence was due to the toxic effects of one or more of the chemicals being used. PMID:5434665

  13. Reactive formulations for a neutralization of toxic industrial chemicals

    DOEpatents

    Tucker, Mark D.; Betty, Rita G.

    2006-10-24

    Decontamination formulations for neutralization of toxic industrial chemicals, and methods of making and using same. The formulations are effective for neutralizing malathion, hydrogen cyanide, sodium cyanide, butyl isocyanate, carbon disulfide, phosgene gas, capsaicin in commercial pepper spray, chlorine gas, anhydrous ammonia gas; and may be effective at neutralizing hydrogen sulfide, sulfur dioxide, formaldehyde, ethylene oxide, methyl bromide, boron trichloride, fluorine, tetraethyl pyrophosphate, phosphorous trichloride, arsine, and tungsten hexafluoride.

  14. Increased Susceptibility to Chemical Toxicity with Pre-existing ...

    EPA Pesticide Factsheets

    Numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest to risk assessors is the potential for chemicals to interact with pre-existing diseases and aging that may yield cumulative damage, altered chemical response, and increased disease susceptibility. We evaluated the relationships between chemicals and pre-existing disease and identify the type of information needed to evaluate the relationships of interest. Key among these is the existence of a clinically relevant and easy to measure biomarker of disease risk which is also modulated by a particular chemical of interest. This biomarker may be a physiological, biochemical, or genetic indicator that corresponds to a phase of the disease process and may be an indicator of where an individual is on the continuum of disease or health status. The relationship between chemical exposure and a biomarker may then be used to predict how preexisting conditions may modify health risks of chemical exposures. Several case studies are explored to describe the toxic chemical, the clinical biomarker, the impacted disease and the evidence that the chemical enhances disease risk: fine particulate matter/decreased heart rate variability/increased cardiopulmonary events; cadmium/decreased glomerular filtration ate/increased chronic kidney disease; methyl mercury/decreased paraoxonase-1/increased cardiovascular risk; Trichloroethylene/increased anti-nuclear antibody/autoimmunit

  15. [Hospital response and medical management in toxic chemical substance disasters].

    PubMed

    Yeh, I-Jeng; Lin, Tzeng-Jih

    2010-06-01

    A hazardous material is defined as any item or agent which has the potential to cause harm to humans, animals, or the environment, either by itself or through interaction with other factors. Toxic chemical substance events are increasingly common events in our modern world. The numerous variables and special equipment involved make effective response to toxic chemical events an especially critical test of hospital emergency response and patient rescue mechanisms. Inadequacies in management could result in disaster - even when only a simple event and minimal error are involved. This article introduces the general medical management algorithm for toxic chemical substance injury and the hospital incident command systems (HICS) developed and currently used by Taiwanese hospitals. Important steps and frequent mistakes made during medical management procedures are further described. The goal of medical care response and emergency units is to prevent catastrophic disasters in the emergency room and their subsequent results. This article further emphasizes correct patient management not only in terms of medical unit effort, but also in terms of cooperation between various relevant organizations including factory-based industrial health and safety systems, multi-factory union defense systems, coordination centers, fire protection and disaster rescue systems, the Environmental Protection Administration and national defense system in order to achieve the most appropriate management. Such coordination, in particular, requires reinforcement in order to ensure readiness for future response needs.

  16. Microbial contamination and chemical toxicity of the Rio Grande

    PubMed Central

    Mendoza, Jose; Botsford, James; Hernandez, Jose; Montoya, Anna; Saenz, Roswitha; Valles, Adrian; Vazquez, Alejandro; Alvarez, Maria

    2004-01-01

    Background The Rio Grande River is the natural boundary between U.S. and Mexico from El Paso, TX to Brownsville, TX. and is one of the major water resources of the area. Agriculture, farming, maquiladora industry, domestic activities, as well as differences in disposal regulations and enforcement increase the contamination potential of water supplies along the border region. Therefore, continuous and accurate assessment of the quality of water supplies is of paramount importance. The objectives of this study were to monitor water quality of the Rio Grande and to determine if any correlations exist between fecal coliforms, E. coli, chemical toxicity as determined by Botsford's assay, H. pylori presence, and environmental parameters. Seven sites along a 112-Km segment of the Rio Grande from Sunland Park, NM to Fort Hancock, TX were sampled on a monthly basis between January 2000 and December 2002. Results The results showed great variability in the number of fecal coliforms, and E. coli on a month-to-month basis. Fecal coliforms ranged between 0–106 CFU/100 ml while E. coli ranged between 6 to > 2419 MPN. H. pylori showed positive detection for all the sites at different times. Toxicity ranged between 0 to 94% of inhibition capacity (IC). Since values above 50% are considered to be toxic, most of the sites displayed significant chemical toxicity at different times of the year. No significant correlations were observed between microbial indicators and chemical toxicity. Conclusion The results of the present study indicate that the 112-Km segment of the Rio Grande river from Sunland Park, NM to Fort Hancock, TX exceeds the standards for contact recreation water on a continuous basis. In addition, the presence of chemical toxicity in most sites along the 112-Km segment indicates that water quality is an area of concern for the bi-national region. The presence of H. pylori adds to the potential health hazards of the Rio Grande. Since no significant correlation was

  17. Multispecies QSAR modeling for predicting the aquatic toxicity of diverse organic chemicals for regulatory toxicology.

    PubMed

    Singh, Kunwar P; Gupta, Shikha; Kumar, Anuj; Mohan, Dinesh

    2014-05-19

    The research aims to develop multispecies quantitative structure-activity relationships (QSARs) modeling tools capable of predicting the acute toxicity of diverse chemicals in various Organization for Economic Co-operation and Development (OECD) recommended test species of different trophic levels for regulatory toxicology. Accordingly, the ensemble learning (EL) approach based classification and regression QSAR models, such as decision treeboost (DTB) and decision tree forest (DTF) implementing stochastic gradient boosting and bagging algorithms were developed using the algae (P. subcapitata) experimental toxicity data for chemicals. The EL-QSAR models were successfully applied to predict toxicities of wide groups of chemicals in other test species including algae (S. obliguue), daphnia, fish, and bacteria. Structural diversity of the selected chemicals and those of the end-point toxicity data of five different test species were tested using the Tanimoto similarity index and Kruskal-Wallis (K-W) statistics. Predictive and generalization abilities of the constructed QSAR models were compared using statistical parameters. The developed QSAR models (DTB and DTF) yielded a considerably high classification accuracy in complete data of model building (algae) species (97.82%, 99.01%) and ranged between 92.50%-94.26% and 92.14%-94.12% in four test species, respectively, whereas regression QSAR models (DTB and DTF) rendered high correlation (R(2)) between the measured and model predicted toxicity end-point values and low mean-squared error in model building (algae) species (0.918, 0.15; 0.905, 0.21) and ranged between 0.575 and 0.672, 0.18-0.51 and 0.605-0.689 and 0.20-0.45 in four different test species. The developed QSAR models exhibited good predictive and generalization abilities in different test species of varied trophic levels and can be used for predicting the toxicities of new chemicals for screening and prioritization of chemicals for regulation.

  18. Acute oral toxicities of wildland fire control chemicals to birds

    USGS Publications Warehouse

    Vyas, N.B.; Spann, J.W.; Hill, E.F.

    2009-01-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24 h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R?) and two Class A fire suppressant foams (Silv-Ex? and Phos-Chek WD881?) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881? and Silv-Ex? were above the predetermined 2000 mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R? because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

  19. Acute oral toxicities of wildland fire control chemicals to birds.

    PubMed

    Vyas, Nimish B; Spann, James W; Hill, Elwood F

    2009-03-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R) and two Class A fire suppressant foams (Silv-Ex and Phos-Chek WD881) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881 and Silv-Ex were above the predetermined 2000mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

  20. The U.S. Environmental Protection Agency strategic plan for evaluating the toxicity of chemicals.

    PubMed

    Firestone, Michael; Kavlock, Robert; Zenick, Hal; Kramer, Melissa

    2010-02-01

    In the 2007 report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences envisioned a major transition in toxicity testing from cumbersome, expensive, and lengthy in vivo testing with qualitative endpoints, to in vitro robotic high-throughput screening with mechanistic quantitative parameters. Recognizing the need for agencies to partner and collaborate to ensure global harmonization, standardization, quality control and information sharing, the U.S. Environmental Protection Agency is leading by example and has established an intra-agency Future of Toxicity Testing Workgroup (FTTW). This workgroup has produced an ambitious blueprint for incorporating this new scientific paradigm to change the way chemicals are screened and evaluated for toxicity. Four main components of this strategy are discussed, as follows: (1) the impact and benefits of various types of regulatory activities, (2) chemical screening and prioritization, (3) toxicity pathway-based risk assessment, and (4) institutional transition. The new paradigm is predicated on the discovery of molecular perturbation pathways at the in vitro level that predict adverse health effects from xenobiotics exposure, and then extrapolating those events to the tissue, organ, or whole organisms by computational models. Research on these pathways will be integrated and compiled using the latest technology with the cooperation of global agencies, industry, and other stakeholders. The net result will be that chemical toxicity screening will become more efficient and cost-effective, include real-world exposure assessments, and eliminate currently used uncertainty factors.

  1. The U.S. EPA's ToxCast Chemical Screening Program and Predictive Modeling of Toxicity

    EPA Science Inventory

    The ToxCast program was developed by the U.S. EPA's National Center for Computational Toxicology to provide cost-effective high-throughput screening for the potential toxicity of thousands of chemicals. Phase I screened 309 compounds in over 500 assays to evaluate concentration-...

  2. CHEMICAL PRIORITIZATION FOR DEVELOPMENTAL TOXICITY USING LITERATURE MINING-BASED WEIGHTING OF TOXCAST ASSAYS

    EPA Science Inventory

    Defining a predictive model of developmental toxicity from in vitro and high-throughput screening (HTS) assays can be limited by the availability of developmental defects data. ToxRefDB (www.epa.gov/ncct/todrefdb) was built from animal studies on data-rich environmental chemicals...

  3. ToxiFly: Can Fruit Flies be Used to Identify Toxicity Pathways for Airborne Chemicals?

    EPA Science Inventory

    Current high-throughput and alternative screening assays for chemical toxicity are unable to test volatile organic compounds (VOCs), thus limiting their scope. Further, the data generated by these assays require mechanistic information to link effects at molecular targets to adve...

  4. The U.S. EPA's ToxCast Chemical Screening Program and Predictive Modeling of Toxicity

    EPA Science Inventory

    The ToxCast program was developed by the U.S. EPA's National Center for Computational Toxicology to provide cost-effective high-throughput screening for the potential toxicity of thousands of chemicals. Phase I screened 309 compounds in over 500 assays to evaluate concentration-...

  5. ToxiFly: Can Fruit Flies be Used to Identify Toxicity Pathways for Airborne Chemicals?

    EPA Science Inventory

    Current high-throughput and alternative screening assays for chemical toxicity are unable to test volatile organic compounds (VOCs), thus limiting their scope. Further, the data generated by these assays require mechanistic information to link effects at molecular targets to adve...

  6. The US EPAs ToxCast Program for the Prioritization and Prediction of Environmental Chemical Toxicity

    EPA Science Inventory

    To meet the need for evaluating large numbers of chemicals for potential toxicity, the U.S. Environmental Protection Agency has initiated a research project call ToxCast that makes use of recent advances in molecular biology and high-throughput screening. These technologies have ...

  7. CHEMICAL PRIORITIZATION FOR DEVELOPMENTAL TOXICITY USING LITERATURE MINING-BASED WEIGHTING OF TOXCAST ASSAYS

    EPA Science Inventory

    Defining a predictive model of developmental toxicity from in vitro and high-throughput screening (HTS) assays can be limited by the availability of developmental defects data. ToxRefDB (www.epa.gov/ncct/todrefdb) was built from animal studies on data-rich environmental chemicals...

  8. The US EPAs ToxCast Program for the Prioritization and Prediction of Environmental Chemical Toxicity

    EPA Science Inventory

    To meet the need for evaluating large numbers of chemicals for potential toxicity, the U.S. Environmental Protection Agency has initiated a research project call ToxCast that makes use of recent advances in molecular biology and high-throughput screening. These technologies have ...

  9. THE UTILIZATION OF THE NTP-HTS DATA IN CHEMICAL TOXICITY MODELING

    EPA Science Inventory

    To explore efficient approaches to assessing the toxicity of environmental chemicals, the NIEHS National Toxicology Program (NTP) recently initiated a High Throughput Screening (HTS) Project. To date, HTS results for a set of 1,408 compounds tested in 6 cell viability assays have...

  10. Combinatorial QSAR modeling of chemical toxicants tested against Tetrahymena pyriformis.

    PubMed

    Zhu, Hao; Tropsha, Alexander; Fourches, Denis; Varnek, Alexandre; Papa, Ester; Gramatica, Paola; Oberg, Tomas; Dao, Phuong; Cherkasov, Artem; Tetko, Igor V

    2008-04-01

    Selecting most rigorous quantitative structure-activity relationship (QSAR) approaches is of great importance in the development of robust and predictive models of chemical toxicity. To address this issue in a systematic way, we have formed an international virtual collaboratory consisting of six independent groups with shared interests in computational chemical toxicology. We have compiled an aqueous toxicity data set containing 983 unique compounds tested in the same laboratory over a decade against Tetrahymena pyriformis. A modeling set including 644 compounds was selected randomly from the original set and distributed to all groups that used their own QSAR tools for model development. The remaining 339 compounds in the original set (external set I) as well as 110 additional compounds (external set II) published recently by the same laboratory (after this computational study was already in progress) were used as two independent validation sets to assess the external predictive power of individual models. In total, our virtual collaboratory has developed 15 different types of QSAR models of aquatic toxicity for the training set. The internal prediction accuracy for the modeling set ranged from 0.76 to 0.93 as measured by the leave-one-out cross-validation correlation coefficient ( Q abs2). The prediction accuracy for the external validation sets I and II ranged from 0.71 to 0.85 (linear regression coefficient R absI2) and from 0.38 to 0.83 (linear regression coefficient R absII2), respectively. The use of an applicability domain threshold implemented in most models generally improved the external prediction accuracy but at the same time led to a decrease in chemical space coverage. Finally, several consensus models were developed by averaging the predicted aquatic toxicity for every compound using all 15 models, with or without taking into account their respective applicability domains. We find that consensus models afford higher prediction accuracy for the

  11. Toxicity and chemical analyses of airport runoff waters in Poland.

    PubMed

    Sulej, Anna Maria; Polkowska, Zaneta; Wolska, Lidia; Cieszynska, Monika; Namieśnik, Jacek

    2014-05-01

    The aim of this study was to assess the ecotoxicological effects of various compounds in complex airport effluents using a chemical and ecotoxicological integrated strategy. The present work deals with the determination of sum of PCBs, PAHs, pesticides, cations, anions, phenols, anionic, cationic, non-ionic detergents, formaldehyde and metals--as well as TOC and conductivity--in runoff water samples collected from 2009 to 2011 at several locations on two Polish international airports. Two microbiotests (Vibrio fischeri bacteria and the crustacean Thamnocephalus platyurus) have been used to determine the ecotoxicity of airport runoff waters. The levels of many compounds exceeded several or even several tens of times the maximum permissible levels. Analysis of the obtained data shows that samples that displayed maximum toxicity towards the bioindicators Vibrio fischeri were not toxic towards Thamnocephalus platyurus. Levels of toxicity towards T. platyurus are strongly correlated with pollutants that originate from the technological operations related to the maintenance of airport infrastructure. The integrated (chemical-ecotoxicological) approach to environmental contamination assessment in and around airports yields extensive information on the quality of the environment. These methodologies can be then used as tools for tracking the environmental fate of these compounds and for assessing the environmental effect of airports. Subsequently, these data will provide a basis for airport infrastructure management.

  12. Biological and Chemical Characterization of Toxic Substances from Candida albicans

    PubMed Central

    Cutler, Jim E.; Friedman, Lorraine; Milner, Kelsey C.

    1972-01-01

    Whole cells, morphological components, and various extracts of Candida albicans were tested for toxicity by methods involving biological activities ordinarily used to characterize bacterial endotoxin. Fungal preparations exerted several of these activities, but only at much higher dose levels than those required for bacterial products. Both fungal cell walls and intact cells were pyrogenic in rabbits and lethal to actinomycin D-treated mice, but only the former were also lethal to chicken embryos; neither coagulated a hemolysate of horseshoe crabs. Wallfree fungal protoplasm was minimally pyrogenic but negative in the other assays. Bacterial endotoxin was strongly active in all four systems. The toxicity of fungous cell walls was undiminished after exposure to strong alkali, a treatment which destroyed bacterial endotoxin. Extracts obtained with hot phenol-water or potassium hydroxide killed mice but were nonpyrogenic. A defatted and enzyme-digested ethylenediamine extract was both lethal and pyrogenic. Particulate fungal materials but not bacterial endotoxin induced a granulomatous response in prepared mice. These data indicate that contaminating bacterial endotoxin was not responsible for the biological effects of fungal products and suggest that C. albicans may contain at least two different toxic components. Chemical analyses were performed on soluble fractions, but a role in toxicity could not be assigned to any identified component. PMID:4564290

  13. A Literature Review - Problem Definition Studies on Selected Toxic Chemicals

    DTIC Science & Technology

    1978-06-16

    toxicity . . . . . . . . . 27 3. Acute gastrointestinal and pulmonary toxicity . . . 28 4. Chronic cutaneous toxicity . . . . . . . . .. . 29 5. Other...cancer . . . . . . . 37 d. gastrointestinal toxicity and cancer . . ... 42 e. general mortality . . . . . . . . . . 42 f. other effects... gastrointestinal toxicity . . . . . . . . .. 45 c. pulmonary toxicity and lung cancer . . . - 46 d. carcinogenicity . . . ........ . 49 IV. ANIMAL TOXICITY

  14. Reduced Toxicity High Performance Monopropellant

    DTIC Science & Technology

    2011-09-01

    distribution unlimited Propellant Performance Characteristics LMP - 103S AF-M315E Hydrazine Flame Temperature 1600ºC 1900ºC 600 oC Isp 252 (theor)235 sec...public release; distribution unlimited Compatibility and Handling Propellant LMP - 103S AF-M315E Thruster Materials Compatibility High combustion...detonation Bikini gauges indicate > 103 kPa @ 50ft Fragments thrown > 185 m Punched hole in end cap 12 Distribution A: Approved for public

  15. Toxic chemicals and thyroid function: hard facts and lateral thinking.

    PubMed

    Duntas, Leonidas H; Stathatos, Nikos

    2015-12-01

    Increasing quantities of evidence-based data incriminate a large number of environmental pollutants for toxic effects on the thyroid. Among the many chemical contaminants, halogenated organochlorines and pesticides variably affect the hypothalamic-pituitary-thyroid axis and disrupt thyroid function. PCBs and their metabolites and PBDEs bind to thyroid transport proteins, such as transthyretin, displace thyroxine, and disrupt thyroid function. Meanwhile, at the molecular level, PCB congeners may activate phosphorylation of Akt, p-Akt, and forkhead box O3a (FoxO3a) protein resulting in inhibition of the natrium/iodide symporter. Given therefore the growing concern developing around these multiple toxic chemicals today invading numerous environments and their long-term deleterious effects not only on the thyroid but also on general health, we strongly advocate their strict regulation and, moreover, their gradual reduction. A good degree of "lateral thinking", we feel, will lead to a use of chemicals that will enhance life while concurrently carefully protecting the environment.

  16. Use of selective chemical extractions as a strategy for the risk assessment in sites with a high level of potentially toxic elements

    NASA Astrophysics Data System (ADS)

    Pérez-Sirvent, Carmen; Martinez Sanchez, Maria Jose; Garcia Lorenzo, Maria Luz; Hernandez Perez, Carmen; Molina Ruiz, Jose; Bech, Jaume

    2016-04-01

    The present study deals with the geochemical fractions of Pb, Cd, Zn and As present on profiles using chemical simple extraction process. This work was conducted on Portman Bay, a site located in the SE Spain and strongly affected by mining activities. Four simple extractions were applied to selected samples in order to evaluate the potential mobility of metals. X-ray diffraction (XRD) and scanning electron microscopy coupled to with an energy-dispersion spectrometry (SEM-EDS) were applied for the characterisation of both the samples and the residues remaining after each extraction, providing additional information about the sediment phases carrying the elements studied. Soil pollution assessment was carried out using the contamination factor (CF) and the pollution load index (PLI) for total contents, and indicators of mobility for each extraction: natural mobility indicator (NMI), acid mine drainage mobility indicator (AMI), oxic mobility indicator (OMI) and anoxic mobility indicator (ANMI). The results obtained after the extractions suggested that the highest PTEs content were extracted in the acidic medium. The mineralogical composition is an important factor that should be taken into account in the evaluation of PTEs mobility, firstly because the mineral phases react differently in the proposed situations depending on their chemical nature, and secondly, because the presence of a particular phase (with different degree of reactivity) depends on the degree of weathering.

  17. Discovery of Chemical Toxicity via Biological Networks and Systems Biology

    SciTech Connect

    Perkins, Edward; Habib, Tanwir; Guan, Xin; Escalon, Barbara; Falciani, Francesco; Chipman, J.K.; Antczak, Philipp; Edwards, Stephen; Taylor, Ronald C.; Vulpe, Chris; Loguinov, Alexandre; Van Aggelen, Graham; Villeneuve, Daniel L.; Garcia-Reyero, Natalia

    2010-09-30

    Both soldiers and animals are exposed to many chemicals as the result of military activities. Tools are needed to understand the hazards and risks that chemicals and new materials pose to soldiers and the environment. We have investigated the potential of global gene regulatory networks in understanding the impact of chemicals on reproduction. We characterized effects of chemicals on ovaries of the model animal system, the Fathead minnow (Pimopheles promelas) connecting chemical impacts on gene expression to circulating blood levels of the hormones testosterone and estradiol in addition to the egg yolk protein vitellogenin. We describe the application of reverse engineering complex interaction networks from high dimensional gene expression data to characterize chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis that governs reproduction in fathead minnows. The construction of global gene regulatory networks provides deep insights into how drugs and chemicals effect key organs and biological pathways.

  18. Chemical Properties And Toxicity of Chromium(III) Nutritional Supplements

    SciTech Connect

    Levina, A.; Lay, P.A.

    2009-05-19

    The status of Cr(III) as an essential micronutrient for humans is currently under question. No functional Cr(III)-containing biomolecules have been definitively described as yet, and accumulated experience in the use of Cr(III) nutritional supplements (such as [Cr(pic){sub 3}], where pic = 2-pyridinecarboxylato) has shown no measurable benefits for nondiabetic people. Although the use of large doses of Cr(III) supplements may lead to improvements in glucose metabolism for type 2 diabetics, there is a growing concern over the possible genotoxicity of these compounds, particularly of [Cr(pic){sub 3}]. The current perspective discusses chemical transformations of Cr(III) nutritional supplements in biological media, with implications for both beneficial and toxic actions of Cr(III) complexes, which are likely to arise from the same biochemical mechanisms, dependent on concentrations of the reactive species. These species include: (1) partial hydrolysis products of Cr(III) nutritional supplements, which are capable of binding to biological macromolecules and altering their functions; and (2) highly reactive Cr(VI/V/IV) species and organic radicals, formed in reactions of Cr(III) with biological oxidants. Low concentrations of these species are likely to cause alterations in cell signaling (including enhancement of insulin signaling) through interactions with the active centers of regulatory enzymes in the cell membrane or in the cytoplasm, while higher concentrations are likely to produce genotoxic DNA lesions in the cell nucleus. These data suggest that the potential for genotoxic side-effects of Cr(III) complexes may outweigh their possible benefits as insulin enhancers, and that recommendations for their use as either nutritional supplements or antidiabetic drugs need to be reconsidered in light of these recent findings.

  19. Evaluation of Chemical Warfare Agent Percutaneous Vapor Toxicity: Derivation of Toxicity Guidelines for Assessing Chemical Protective Ensembles.

    SciTech Connect

    Watson, A.P.

    2003-07-24

    Percutaneous vapor toxicity guidelines are provided for assessment and selection of chemical protective ensembles (CPEs) to be used by civilian and military first responders operating in a chemical warfare agent vapor environment. The agents evaluated include the G-series and VX nerve agents, the vesicant sulfur mustard (agent HD) and, to a lesser extent, the vesicant Lewisite (agent L). The focus of this evaluation is percutaneous vapor permeation of CPEs and the resulting skin absorption, as inhalation and ocular exposures are assumed to be largely eliminated through use of SCBA and full-face protective masks. Selection of appropriately protective CPE designs and materials incorporates a variety of test parameters to ensure operability, practicality, and adequacy. One aspect of adequacy assessment should be based on systems tests, which focus on effective protection of the most vulnerable body regions (e.g., the groin area), as identified in this analysis. The toxicity range of agent-specific cumulative exposures (Cts) derived in this analysis can be used as decision guidelines for CPE acceptance, in conjunction with weighting consideration towards more susceptible body regions. This toxicity range is bounded by the percutaneous vapor estimated minimal effect (EME{sub pv}) Ct (as the lower end) and the 1% population threshold effect (ECt{sub 01}) estimate. Assumptions of exposure duration used in CPE certification should consider that each agent-specific percutaneous vapor cumulative exposure Ct for a given endpoint is a constant for exposure durations between 30 min and 2 hours.

  20. Toxicity Appraisal of Untreated Dyeing Industry Wastewater Based on Chemical Characterization and Short Term Bioassays.

    PubMed

    Akhtar, Muhammad Furqan; Ashraf, Muhammad; Javeed, Aqeel; Anjum, Aftab Ahmad; Sharif, Ali; Saleem, Ammara; Akhtar, Bushra; Khan, Abdul Muqeet; Altaf, Imran

    2016-04-01

    Characterizing wastewaters only on a chemical basis may be insufficient owing to their complex nature. The purpose of this study was to assess toxicity of textile dyeing wastewater based on analytical techniques and short term toxicity based bioassays. In this study, screening of the fractionated wastewater through GC-MS showed the presence of phenols, phthalic acid derivatives and chlorpyrifos. Metal analysis revealed that chromium, arsenic and mercury were present in amounts higher than the wastewater discharge limits. Textile dyeing wastewater was found to be highly mutagenic in the Ames test. DNA damage in sheep lymphocytes decreased linearly with an increase in the dilution of wastewater. MTT assay showed that 8.3 percent v/v wastewater decreased cell survival percentage to 50 %. It can be concluded from this study that short term toxicity tests such as Ames test, in vitro comet assay, and cytotoxicity assays may serve as useful indicators of wastewater pollution along with their organic and inorganic chemical characterizations.

  1. Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

    PubMed

    Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

    2013-01-01

    Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

  2. The chemical exposure toxicity space (CETS) model: Displaying exposure time, aqueous and organic concentration, activity, and onset of toxicity

    PubMed Central

    Mackay, Donald; Parnis, J. Mark; McCarty, Lynn S.; Arnot, Jon A.; Powell, David E.

    2016-01-01

    Abstract A 1‐compartment toxicokinetic model is used to characterize the chemical exposure toxicity space (CETS), providing a novel graphic tool that can aid in the design of aquatic toxicity tests for fish and for interpreting their results. The graph depicts the solution to the differential equation describing the uptake kinetics of a chemical by a modeled fish under conventional bioassay conditions. The model relates the exposure concentration in the water to a dimensionless time and the onset of toxicity as determined by an estimated or assumed critical body residue or incipient lethal aqueous concentration. These concentration graphs are specific to each chemical and exposure and organism parameters and clearly demonstrate differences in toxicity between chemicals and how factors such as hydrophobicity influence the toxic endpoint. The CETS plots can also be used to assess bioconcentration test conditions to ensure that concentrations are well below toxic levels. Illustrative applications are presented using a recent set of high‐quality toxicity data. Conversion of concentrations to chemical activities in the plots enables results for different baseline toxicants to be superimposed. For chemicals that have different modes of toxic action, the increased toxicity then becomes apparent. Implications for design and interpretation of aquatic toxicity tests are discussed. The model, and pictorial visualization of the time‐course of aquatic toxicity tests, may contribute to improvements in test design, implementation, and interpretation, and to reduced animal usage. Environ Toxicol Chem 2017;36:1389–1396. © 2016 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC. PMID:27801500

  3. 40 CFR 372.22 - Covered facilities for toxic chemical release reporting.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Covered facilities for toxic chemical... (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS TOXIC CHEMICAL RELEASE REPORTING: COMMUNITY RIGHT-TO-KNOW Reporting Requirements § 372.22 Covered facilities for toxic...

  4. A new technique for screening chemical toxicity to the pulp from dental restorative materials and procedures.

    PubMed

    Hume, W R

    1985-11-01

    An in vitro test system is described which allows for quick and relatively inexpensive examination of the potential for chemical toxicity to the pulp of materials and procedures used in the restoration of single teeth. The test system consisted of two sequential steps. First, a restorative procedure was carried out on a freshly-extracted human tooth crown, to the pulpal surface of which had been attached a chamber filled with sterile tissue-culture medium. The preparation was kept at 37 degrees C. The culture medium was removed at day one and replaced with fresh medium, which was removed at day 3. In the second step, we used a standard tissue-culture toxicity assessment technique to examine both culture medium samples for the presence of chemical toxins. In use, this system gave results which correlated well with the known clinical potential for pulpal toxicity of various dental materials and techniques. For example, zinc oxide-eugenol used as temporary filling or base had no apparent potential for toxicity. Sealing a cotton pellet containing phenol into a cavity was of high apparent potential toxicity. Acrylic resin as intracoronal or extracoronal fillings showed potential for toxicity; this potential was decreased by lining with calcium hydroxide cement. Composite resin placed onto etched dentin had apparent toxic potential, but had less such potential when placed onto unetched dentin. The technique had some advantages over previously described in vitro toxicity test for restorative materials, because it included a step requiring diffusion of potential toxins into and through human dentin, and because it allowed for examination of variations in technique which mimic clinical behavior, and of materials used in sequence or in combination.

  5. Characterization of ZnS thin films synthesized through a non-toxic precursors chemical bath

    SciTech Connect

    Rodríguez, C.A.; Sandoval-Paz, M.G.; Cabello, G.; Flores, M.; Fernández, H.; Carrasco, C.

    2014-12-15

    Highlights: • High quality ZnS thin films have been deposited by chemical bath deposition technique from a non-toxic precursor’s solution. • Nanocrystalline ZnS thin films with large band gap energy were synthesized without using ammonia. • Evidence that the growing of the thin films is carried out by means of hydroxide mechanism was found. • The properties of these ZnS thin films are similar and in some cases better than the corresponding ones produced using toxic precursors such as ammonia. - Abstract: In solar cells, ZnS window layer deposited by chemical bath technique can reach the highest conversion efficiency; however, precursors used in the process normally are materials highly volatile, toxic and harmful to the environment and health (typically ammonia and hydrazine). In this work the characterization of ZnS thin films deposited by chemical bath in a non-toxic alkaline solution is reported. The effect of deposition technique (growth in several times) on the properties of the ZnS thin film was studied. The films exhibited a high percentage of optical transmission (greater than 80%); as the deposition time increased a decreasing in the band gap values from 3.83 eV to 3.71 eV was observed. From chemical analysis, the presence of ZnS and Zn(OH){sub 2} was identified and X-ray diffraction patterns exhibited a clear peak corresponding to ZnS hexagonal phase (1 0 3) plane, which was confirmed by electron diffraction patterns. From morphological studies, compact samples with well-defined particles, low roughness, homogeneous and pinhole-free in the surface were observed. From obtained results, it is evident that deposits of ZnS–CBD using a non-toxic solution are suitable as window layer for TFSC.

  6. Acute toxicity of fire-control chemicals, nitrogenous chemicals, and surfactants to rainbow trout

    USGS Publications Warehouse

    Buhl, Kevin J.; Hamilton, Steven J.

    2000-01-01

    Laboratory studies were conducted to determine the acute toxicity of three ammonia-based fire retardants (Fire-Trol LCA-F, Fire-Trol LCM-R, and Phos-Chek 259F), five surfactant-based fire-suppressant foams (FireFoam 103B, FireFoam 104, Fire Quench, ForExpan S, and Pyrocap B-136), three nitrogenous chemicals (ammonia, nitrate, and nitrite), and two anionic surfactants (linear alkylbenzene sulfonate [LAS] and sodium dodecyl sulfate [SDS]) to juvenile rainbow trout Oncorhynchus mykiss in soft water. The descending rank order of toxicity (96-h concentration lethal to 50% of test organisms [96-h LC50]) for the fire retardants was as follows: Phos-Chek 259F (168 mg/L) > Fire-Trol LCA-F (942 mg/L) = Fire-Trol LCM-R (1,141 mg/L). The descending rank order of toxicity for the foams was as follows: FireFoam 103B (12.2 mg/L) = FireFoam 104 (13.0 mg/L) > ForExpan S (21.8 mg/L) > Fire Quench (39.0 mg/L) > Pyrocap B-136 [156 mg/L). Except for Pyrocap B-136, the foams were more toxic than the fire retardants. Un-ionized ammonia (NH3; 0.125 mg/L as N) was about six times more toxic than nitrite (0.79 mg/L NO2-N) and about 13,300 times more toxic than nitrate (1,658 mg/L NO3-N). Linear alkylbenzene sulfonate (5.0 mg/L) was about five times more toxic than SDS (24.9 mg/L). Estimated total ammonia and NH3 concentrations at the 96-h LC50s of the fire retardants indicated that ammonia was the primary toxic component in these formulations. Based on estimated anionic surfactant concentrations at the 96-h LC50s of the foams and reference surfactants, LAS was intermediate in toxicity and SDS was less toxic to rainbow trout when compared with the foams. Comparisons of recommended application concentrations to the test results indicate that accidental inputs of these chemicals into streams require substantial dilutions (100-1,750-fold to reach concentrations nonlethal to rainbow trout.

  7. New Chemicals Exposure Limits section 5(e) Order Boilerplate insert under the Toxic Substances Control Act (TSCA) New Chemicals Program

    EPA Pesticide Factsheets

    The New Chemicals Exposure Limits (NCELs) section 5(e) Consent Order insert presents the standard NCELs provisions. The actual NCEL concentration is an empty blank to be completed depending on the toxicity of the specific chemical involved.

  8. 76 FR 1067 - Testing of Certain High Production Volume Chemicals; Second Group of Chemicals

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-07

    ... physical/chemical properties and biodegradation); ecotoxicity (in fish, Daphnia, and algae); acute toxicity... toxicity (gene mutations and chromosomal aberrations). Ecotoxicity (studies in fish, Daphnia, and algae..., Daphnia, and algae); acute toxicity; genetic toxicity (gene mutations and chromosomal aberrations);...

  9. Chemical properties and toxicity of soils contaminated by mining activity.

    PubMed

    Agnieszka, Baran; Tomasz, Czech; Jerzy, Wieczorek

    2014-09-01

    This research is aimed at assessing the total content and soluble forms of metals (zinc, lead and cadmium) and toxicity of soils subjected to strong human pressure associated with mining of zinc and lead ores. The research area lay in the neighbourhood of the Bolesław Mine and Metallurgical Plant in Bukowno (Poland). The study obtained total cadmium concentration between 0.29 and 51.91 mg, zinc between 7.90 and 3,614 mg, and that of lead between 28.4 and 6844 mg kg(-1) of soil d.m. The solubility of the heavy metals in 1 mol dm(-3) NH4NO3 was 1-49% for zinc, 5-45% for cadmium, and <1-10% for lead. In 1 mol HCl dm(-3), the solubility of the studied metals was much higher and obtained values depending on the collection site, from 45 to 92% for zinc, from 74 to 99%, and from 79 to 99% for lead. The lower solubility of the heavy metals in 1 mol dm(-3) NH4NO3 than 1 mol HCl dm(-3) is connected with that, the ammonium nitrate has low extraction power, and it is used in determining the bioavailable (active) form of heavy metals. Toxicity assessment of the soil samples was performed using two tests, Phytotoxkit and Microtox(®). Germination index values were between 22 and 75% for Sinapis alba, between 28 and 100% for Lepidium sativum, and between 10 and 28% for Sorghum saccharatum. Depending on the studied soil sample, Vibrio fischeri luminescence inhibition was 20-96%. The sensitivity of the test organisms formed the following series: S. saccharatum > S. alba = V. fischeri > L. sativum. Significant positive correlations (p ≤ 0.05) of the total and soluble contents of the metals with luminescence inhibition in V. fischeri and root growth inhibition in S. saccharatum were found. The general trend observed was an increase in metal toxicity measured by the biotest with increasing available metal contents in soils. All the soil samples were classified into toxicity class III, which means that they are toxic and present severe danger. Biotest are a good complement to

  10. 75 FR 8575 - Testing of Certain High Production Volume Chemicals; Third Group of Chemicals

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-25

    ...EPA is proposing a test rule under section 4(a)(1)(B) of the Toxic Substances Control Act (TSCA) that would require manufacturers, importers, and processors of certain high production volume (HPV) chemicals to conduct testing to obtain screening level data for health and environmental effects and chemical fate.

  11. Predicting acute aquatic toxicity of structurally diverse chemicals in fish using artificial intelligence approaches.

    PubMed

    Singh, Kunwar P; Gupta, Shikha; Rai, Premanjali

    2013-09-01

    The research aims to develop global modeling tools capable of categorizing structurally diverse chemicals in various toxicity classes according to the EEC and European Community directives, and to predict their acute toxicity in fathead minnow using set of selected molecular descriptors. Accordingly, artificial intelligence approach based classification and regression models, such as probabilistic neural networks (PNN), generalized regression neural networks (GRNN), multilayer perceptron neural network (MLPN), radial basis function neural network (RBFN), support vector machines (SVM), gene expression programming (GEP), and decision tree (DT) were constructed using the experimental toxicity data. Diversity and non-linearity in the chemicals' data were tested using the Tanimoto similarity index and Brock-Dechert-Scheinkman statistics. Predictive and generalization abilities of various models constructed here were compared using several statistical parameters. PNN and GRNN models performed relatively better than MLPN, RBFN, SVM, GEP, and DT. Both in two and four category classifications, PNN yielded a considerably high accuracy of classification in training (95.85 percent and 90.07 percent) and validation data (91.30 percent and 86.96 percent), respectively. GRNN rendered a high correlation between the measured and model predicted -log LC50 values both for the training (0.929) and validation (0.910) data and low prediction errors (RMSE) of 0.52 and 0.49 for two sets. Efficiency of the selected PNN and GRNN models in predicting acute toxicity of new chemicals was adequately validated using external datasets of different fish species (fathead minnow, bluegill, trout, and guppy). The PNN and GRNN models showed good predictive and generalization abilities and can be used as tools for predicting toxicities of structurally diverse chemical compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Toxic industrial chemicals and chemical weapons: exposure, identification, and management by syndrome.

    PubMed

    Tomassoni, Anthony J; French, Robert N E; Walter, Frank G

    2015-02-01

    Toxidromes aid emergency care providers in the context of the patient presenting with suspected poisoning, unexplained altered mental status, unknown hazardous materials or chemical weapons exposure, or the unknown overdose. The ability to capture an adequate chemical exposure history and to recognize toxidromes may reduce dependence on laboratory tests, speed time to delivery of specific antidote therapy, and improve selection of supportive care practices tailored to the etiologic agent. This article highlights elements of the exposure history and presents selected toxidromes that may be caused by toxic industrial chemicals and chemical weapons. Specific antidotes for toxidromes and points regarding their use, and special supportive measures, are presented. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Directory of public libraries. Toxic chemical release inventory

    SciTech Connect

    Not Available

    1990-02-01

    The Directory of Public Libraries is a compilation of over 2,300 libraries designated by each State's Librarian to receive their state's microfiche containing data collected under Section 313 (j) of the Emergency Planning and Community Right-to-Know Act (EPCRA) Title III of the Superfund Amendments and Reauthorization Act of 1986--Public Law 99-499. Section 313 (j) of EPCRA requires EPA to establish the National Toxic Chemical Release Inventory (TRI) and to make the data/information collected annually available to the public through computer telecommunications and other means. TRI is distributed, sold and available in many different forms--online through the National Library of Medicine, CD-ROM, dBase, and Lotus floppy diskettes, microfiche, magnetic tape. It is accessible to the public in one or more of these forms from thousands of locations nationwide, as well as several international locations, of which this Directory identifies over 40% of those locations.

  14. Picking Cell Lines for High-Throughput Transcriptomic Toxicity Screening (SOT)

    EPA Science Inventory

    High throughput, whole genome transcriptomic profiling is a promising approach to comprehensively evaluate chemicals for potential biological effects. To be useful for in vitro toxicity screening, gene expression must be quantified in a set of representative cell types that captu...

  15. Radiation-dosimetry and chemical-toxicity considerations for /sup 99/Tc

    SciTech Connect

    Coffey, J.L.; Hayes, R.L.; Rafter, J.J.; Watson, E.E.; Carlton, J.E.

    1982-01-01

    Technetium-99 (T/sub 1/2/ = 2.13 x 10/sup 5/ y) is produced in the fission of /sup 235/U and /sup 239/Pu. Technitium-99 has been found to contaminate some areas of the uranium re-enrichment process. ICRP-30 Part 2 gives the Annual Limit on Intake (ALI) for /sup 99/Tc as 2 x 10/sup 8/ Bq (5.4 mCi) for class D inhaled material (IC80). The ICRP states clearly that ALIs are based on radiation risk only and that chemical toxicity is not considered (IC79). No data wer found on the chemical toxicity of /sup 99/Tc, possibly because there are no stable isotopes of technetium with which to study the toxicity, although, because of its long T/sub 1/2/, /sup 99/Tc can, for all practical purposes, be considered stable. The ALI values for /sup 99/Tc are based on data obtained using high specific activity /sup 99m/Tc (T/sub 1/2/ = 6 h) and /sup 95m/Tc (T/sub 1/2/ = 61 days). Since the specific activities of /sup 99/Tc and Na/sup 99/TcO/sub 4/ are quite low (17 mCi/g and 9 mCi/g, respectively) and /sup 99/Tc is available in abundant supply, we have attempted to assess the relative radiation and chemical hazards that are associated with this radionuclide. The approach in this study was (1) to study the effect of chemical dose on the whole body retention of /sup 99/Tc sodium pertechnetate in rats and to relate these effects to the radiation dose and the ALI and (2) to compare the chemical toxicity of /sup 99/Tc sodium pertechnetate with the ALI at different chemical dose levels.

  16. Mechanical-chemical analyses and sub-chronic systemic toxicity of chemical treated organic bovine bone.

    PubMed

    Lee, Kwang-il; Lee, Jung-soo; Lee, Keun-soo; Jung, Hong-hee; Ahn, Chan-min; Kim, Young-sik; Shim, Young-bock; Jang, Ju-woong

    2015-12-01

    Sequentially chemical-treated bovine bone was not only evaluated by mechanical and chemical analyses but also implanted into the gluteal muscles of rats for 12 weeks to investigate potential local pathological effects and systemic toxicities. The test (chemical treated bone) and control (heat treated bone) materials were compared using scanning electron microscope (SEM), x-ray diffraction pattern, inductively coupled plasma analysis, and bending strength test. In the SEM images, the micro-porous structure of heat-treated bone was changed to sintered ceramic-like structure. The structure of bone mineral from test and control materials was analyzed as100% hydroxyapatite. The ratio of calcium (Ca) to potassium (P), the main inorganic elements, was same even though the Ca and P percentages of the control material was relatively higher than the test material. No death or critical symptoms arose from implantation of the test (chemical treated bone) and control (physiological saline) materials during 12 weeks. The implanted sites were macroscopically examined, with all the groups showing non-irritant results. Our results indicate that chemical processed bovine bone has a better mechanical property than the heat treated bone and the implantation of this material does not produce systemic or pathological toxicity.

  17. Comparing rapid-screening and standard toxicity assays to assess known chemical contamination at a hazardous waste site

    SciTech Connect

    Martino, L.; Swigert, J.; Roberts, C.

    1995-12-31

    The thrust to streamline the Superfund site investigation/remediation program makes it critical for site investigators to utilize rapid screening methodologies to facilitate decision-making. However, screening methodologies providing information upon which decision-making is based must not only be rapid but also scientifically valid. This presentation compares and contrasts two rapid screening toxicity assessments, the Daphnia magna IQ Toxicity Test {trademark} and Microtox{trademark}, to a battery of standard aquatic toxicity tests using Lemna, Rana, Pimephales, Selenastruni and Ceriodaphnia. Chemical analysis of test water samples provided evidence of potential toxicological risk associated with the test samples. The study site was J-Field, Aberdeen Proving Ground, Maryland, a federal facility listed on the National Priority List that used to test and/or dispose of high explosives and chemical warfare agents in open pits or fields. Surface water samples from 20 sites were collected and used in the toxicity assessments. Water samples also were analyzed for explosives, chemical surety degradation compounds, Target Analyte List (inorganics), Target Compound List (organics) and selected pesticides and PCBs. The Microtox{trademark} assay did not reveal any toxicity present in the samples analyzed. Correlation analyses showed only slight correlation between the Daphnia magna IQ{trademark} assay and the standard 48-hour toxicity test. No correlation existed between the Microtox{trademark} assay and the aquatic toxicity tests. Results are discussed in light of the expected risk of the chemicals known to be present and the outcome of the toxicity tests.

  18. A high throughput respirometric assay for mitochondrial biogenesis and toxicity

    PubMed Central

    Beeson, Craig C.; Beeson, Gyda C.; Schnellmann, Rick G.

    2010-01-01

    Mitochondria are a common target of toxicity for drugs and other chemicals, and results in decreased aerobic metabolism and cell death. In contrast, mitochondrial biogenesis restores cell vitality and there is a need for new agents to induce biogenesis. Current cell-based models of mitochondrial biogenesis or toxicity are inadequate because cultured cell lines are highly glycolytic with minimal aerobic metabolism and altered mitochondrial physiology. In addition, there are no high-throughput, real-time assays that assess mitochondrial function. We adapted primary cultures of renal proximal tubular cells (RPTC) that exhibit in vivo levels of aerobic metabolism, are not glycolytic, and retain higher levels of differentiated functions and used the Seahorse Biosciences analyzer to measure mitochondrial function in real time in multi-well plates. Using uncoupled respiration as a marker of electron transport chain (ETC) integrity, the nephrotoxicants cisplatin, HgCl2 and gentamicin exhibited mitochondrial toxicity prior to decreases in basal respiration and cell death. Conversely, using FCCP-uncoupled respiration as a marker of maximal ETC activity, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), SRT1720, resveratrol, daidzein, and metformin produced mitochondrial biogenesis in RPTC. The merger of the RPTC model and multi-well respirometry results in a single high throughput assay to measure mitochondrial biogenesis and toxicity, and nephrotoxic potential. PMID:20465991

  19. Changes of chemical chronic toxicity to Daphnia magna under different food regimes.

    PubMed

    Pavlaki, Maria D; Ferreira, Abel L G; Soares, Amadeu M V M; Loureiro, Susana

    2014-11-01

    In aquatic ecosystems several stressors may act together and affect the life traits of organisms. Pesticide runoffs are usually associated with high inputs of organic matter and depletion of oxygen in aquatic systems. This study aimed at combining anthropogenic stress (chemicals) and natural stress (food availability) and evaluates their joint effect to the life traits of Daphnia magna. The neonicotinoid insecticide imidacloprid and the heavy metal nickel chloride were used and a 21 d chronic test was carried out to obtain reproduction and growth data. The conceptual model Independent action, usually used for assessing response patterns in chemical mixtures, was used for data interpretation. Results showed an increase in the reproduction and growth pattern of D. magna as food levels increased. Both chemicals significantly impaired the reproduction as well as the somatic growth of the organism while the same happened with food concentrations lower than 3×10(5) cells/mL. It was also observed that food availability did not change the toxicity of imidacloprid and nickel chloride when food levels were higher than 3×10(5) cells/mL. When combined with low food levels, imidacloprid showed a slight increase in toxicity, showing that daphnids become more sensitive with reduced food availability, however in a non-significant way. However, toxicity of nickel appeared to be independent of the food level. Both chemicals induced mortality to the organisms exposed in the absence of food only at the end of the test. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Toxic chemical considerations for tank farm releases. Revision 1

    SciTech Connect

    Van Keuren, J.C.

    1995-11-01

    This document provides a method of determining the toxicological consequences of accidental releases from Hanford Tank Farms. A determination was made of the most restrictive toxic chemicals that are expected to be present in the tanks. Concentrations were estimated based on the maximum sample data for each analyte in all the tanks in the composite. Composite evaluated were liquids and solids from single shell tanks, double shell tanks, flammable gas watch list tanks, as well as all solids, all liquids, head space gases, and 241-C-106 solids. A sum of fractions of the health effects was computed for each composite for unit releases based emergency response planning guidelines (ERPGs). Where ERPGs were not available for chemical compounds of interest, surrogate guidelines were established. The calculation method in this report can be applied to actual release scenarios by multiplying the sum of fractions by the release rate for continuous releases, or the release amount for puff releases. Risk guidelines are met if the product is less than for equal to one.

  1. Aquatic toxicity of PAHs and PAH mixtures at saturation to benthic amphipods: linking toxic effects to chemical activity.

    PubMed

    Engraff, Maria; Solere, Clémentine; Smith, Kilian E C; Mayer, Philipp; Dahllöf, Ingela

    2011-04-01

    Organisms in marine sediments are usually exposed to mixtures of polycyclic aromatic hydrocarbons (PAHs), whereas risk assessment and management typically focus on the effects of single PAHs. This can lead to an underestimation of risk if the effects of single compounds are additive or synergistic. Because of the virtually infinite number of mixture-combinations, and the many different targeted organisms, it would be advantageous to have a model for the assessment of mixture effects. In this study we tested whether chemical activity, which drives the partitioning of PAHs into organisms, can be used to model the baseline toxicity of mixtures. Experiments were performed with two benthic amphipod species (Orchomonella pinguis and Corophium volutator), using passive dosing to control the external exposure of single PAHs and mixtures of three and four PAHs. The baseline toxicity of individual PAHs at water saturation generally increased with increasing chemical activity of the PAHs. For O. pinguis, the baseline toxicity of PAH mixtures was successfully described by the sum of chemical activities. Some compounds and mixtures showed a delayed expression of toxicity, highlighting the need to adjust the length of the experiment depending on the organism. On the other hand, some of the single compounds had a higher toxicity than expected, possibly due to the toxicity of PAH metabolites. We suggest that chemical activity of mixtures can, and should, be used in addition to toxicity data for single compounds in environmental risk assessment.

  2. High dose insulin in toxic cardiogenic shock.

    PubMed

    Holger, Joel S; Engebretsen, Kristin M; Marini, John J

    2009-04-01

    To report the successful use of high dose insulin (HDI) in previously unreported insulin dosing ranges in a patient with severe myocardial toxicity due to an amitriptyline and citalopram overdose. A 65-year-old female presented in respiratory arrest, which was followed by bradycardic pulseless electrical activity after ingesting multiple medications. After a prolonged resuscitation, the patient was maintained only on infusions of norepinephrine (40 mcg/min), vasopressin (4 units/h), insulin (80 units/h), and sodium bicarbonate. Due to a deteriorating clinical condition and limited prognosis, the insulin infusion was titrated incrementally upwards to 600 units/h (6 units/kg/h) over a 5 h time period while simultaneously completely weaning off both vasopressors. She developed brisk pulses and warm extremities, and her cardiac output nearly tripled. After 2 days of stabilization the insulin was slowly tapered, and the patient recovered. HDI as a single cardiovascular agent significantly improved clinical and cardiovascular parameters after the failure of vasopressor therapy in severe cardiovascular toxicity. Higher doses of insulin than previously recommended may be needed in toxic poisonings when severe myocardial depression is present.

  3. [Risk assessment and risk control for occupational exposure to chemical toxicants from an isophorone nitrile device].

    PubMed

    Wang, Dejun; Fu, Xiaokuan; Kong, Fanling; Sui, Shaofeng; Jiang, Yuanyuan; Du, Yinglin; Zhou, Jingyang

    2014-06-01

    Risk assessment and risk control for occupational exposure to chemical toxicants were performed on an isophorone nitrile device with an annual production of 5,000 tons, based on improved Singaporean semi-quantitative risk assessment method, with consideration of actual situation in China and in the present project. With the use of engineering analysis and identification of occupational hazards in the improved Singaporean semi-quantitative risk assessment method, hazard rating (HR) and risk assessment were performed on chemical toxicants from an isophorone nitrile device with an annual production of 5,000 tons. The chemical toxicants in the isophorone nitrile device were mainly isophorone, hydrocyanic acid, methanol, phosphoric acid, sodium hydroxide, and sodium cyanide; the HR values were mild hazard (2), extreme hazard (5), mild hazard (2), mild hazard (2), moderate hazard (3), and extreme hazard (5), respectively, and the corresponding exposure rating (ER) values were 2.09, 2.72, 2.76, 1.68, 2.0, and 1.59, respectively. The risk of chemical toxicants in this project was assessed according to the formula Risk = [HR×ER](1/2). Hydrocyanic acid was determined as high risk, sodium hydroxide and sodium cyanide as medium risk, and isophorone, methanol, and phosphoric acid as low risk. Priority in handling of risks was determined by risk rating. The table of risk control measure was established for pre-assessment of occupational hazards. With risk assessment in this study, we concluded that the isophorone nitrile device with 5,000 ton annual production was a high-occupational hazard device. This device is a project of extreme occupational hazard. The improved Singaporean semi-quantitative risk assessment method is a scientific and applicable method, and is especially suitable for pre-evaluation of on-site project with no analogy.

  4. STRUCTURE-ACTIVITY RELATIONSHIP STUIDES AND THEIR ROLE IN PREDICTING AND INVESTIGATING CHEMICAL TOXICITY

    EPA Science Inventory

    Structure-Activity Relationship Studies and their Role in Predicting and Investigating Chemical Toxicity

    Structure-activity relationships (SAR) represent attempts to generalize chemical information relative to biological activity for the twin purposes of generating insigh...

  5. STRUCTURE-ACTIVITY RELATIONSHIP STUIDES AND THEIR ROLE IN PREDICTING AND INVESTIGATING CHEMICAL TOXICITY

    EPA Science Inventory

    Structure-Activity Relationship Studies and their Role in Predicting and Investigating Chemical Toxicity

    Structure-activity relationships (SAR) represent attempts to generalize chemical information relative to biological activity for the twin purposes of generating insigh...

  6. Inhalation toxicity of high flash aromatic naphtha.

    PubMed

    Clark, D G; Butterworth, S T; Martin, J G; Roderick, H R; Bird, M G

    1989-05-01

    A petroleum distillate--a high aromatic naphtha--consisting of a 50/50 blended mixture of equivalent products. SHELLSOL A* and SOLVESSO 100**, containing C9 isomers (75 percent) particularly trimethyl benzenes, was examined for systemic toxicity in rats by inhalation exposure. A preliminary 13-week inhalation study with SHELLSOL A had resulted in liver and kidney weight increases in female rats at the high (7400 mg/m3) and medium (3700 mg/m3) exposure levels, and a low grade anaemia in females at all exposure levels (7400, 3700 and 1800 mg/m3). The follow-up 12-month inhalation study in rats described here used atmosphere generated from the SHELLSOL A/SOLVESSO 100 blend of 1800, 900 and 450 mg/m3. Initial reduction in body weight gain occurred in both male and female rats at the higher exposures. Various statistically significant haematological changes were transiently seen in males up to six months, but were not considered biologically significant. High exposure male liver and kidney weights were increased at 6 and 12 months but, in the absence of histopathological changes, were considered to be physiological adaptive responses. No treatment-related histopathological abnormalities were found. It is concluded that chronic exposure to this high aromatic naphtha is without systemic toxicity in rats under the conditions of these studies.

  7. Multiple reporter gene assays for the assessment and estimation of chemical toxicity.

    PubMed

    Takahashi, Junko; Iwahashi, Hitoshi

    2004-01-01

    To detect chemical toxicity, we are making new bioassay systems that use promoters selected from yeast DNA microarray experiments. We performed multiple reporter gene assays using the promoters of these genes; the promoter regions were inserted upstream of green fluorescence protein (GFP). In this report, six genes (HSP26, MET17, YLL057C, FIT2, CUP1 and OYE3) were selected and assays were carried out for 55 chemicals. The promoters of these genes showed different responses to chemicals within 4 h. This result indicates that this technique enables us to predict the toxicity of chemicals in the environment and to understand toxicities of newly synthesized chemicals.

  8. Acute Toxicity Estimation and Operational Risk Management of Chemical Warfare Agent Exposures

    DTIC Science & Technology

    2004-05-01

    December 2001 Deputy Assistant to The Secretary of Defense Chemical and Biological (Warfare Agent) Defense ((DATSD- CBD ) interim-certified acute...avoidance (detection), protection, decontamination, and medical intervention. d. Compares the DATSD- CBD interim-certified acute toxicity values...defense. 2. CONCLUSIONS AND RECOMMENDATIONS. a. Translating Toxicity Information into ORM Terminology. The 2001 DATSD- CBD toxicity

  9. Environmental Pollution, Toxicity Profile and Treatment Approaches for Tannery Wastewater and Its Chemical Pollutants.

    PubMed

    Saxena, Gaurav; Chandra, Ram; Bharagava, Ram Naresh

    Leather industries are key contributors in the economy of many developing countries, but unfortunately they are facing serious challenges from the public and governments due to the associated environmental pollution. There is a public outcry against the industry due to the discharge of potentially toxic wastewater having alkaline pH, dark brown colour, unpleasant odour, high biological and chemical oxygen demand, total dissolved solids and a mixture of organic and inorganic pollutants. Various environment protection agencies have prioritized several chemicals as hazardous and restricted their use in leather processing however; many of these chemicals are used and discharged in wastewater. Therefore, it is imperative to adequately treat/detoxify the tannery wastewater for environmental safety. This paper provides a detail review on the environmental pollution and toxicity profile of tannery wastewater and chemicals. Furthermore, the status and advances in the existing treatment approaches used for the treatment and/or detoxification of tannery wastewater at both laboratory and pilot/industrial scale have been reviewed. In addition, the emerging treatment approaches alone or in combination with biological treatment approaches have also been considered. Moreover, the limitations of existing and emerging treatment approaches have been summarized and potential areas for further investigations have been discussed. In addition, the clean technologies for waste minimization, control and management are also discussed. Finally, the international legislation scenario on discharge limits for tannery wastewater and chemicals has also been discussed country wise with discharge standards for pollution prevention due to tannery wastewater.

  10. Monitoring and trace detection of hazardous waste and toxic chemicals using resonance Raman spectroscopy

    SciTech Connect

    Sedlacek, A.J. III; Dougherty, D.R.; Chen, C.L.

    1993-01-01

    Raman scattering is a coherent, inelastic, two-photon process, which shifts the frequency of an outgoing photon according to the vibrational structure of the irradiated species, thereby providing a unique fingerprint of the molecule. When involving an allowed electronic transition (resonance Raman), this scattering cross section can be enhanced by 10[sup 4] to 10[sup 6] and provides the basis for a viable technique that can monitor and detect trace quantities of hazardous wastes and toxic chemicals. Resonance Raman spectroscopy (RRS) possesses many of the ideal characteristics for monitoring and detecting of hazardous waste and toxic chemicals. Some of these traits are: (1) very high selectivity (chemical specific fingerprints); (2) independence from the excitation wavelength (ability to monitor in the solar blind region); (3) chemical mixture fingerprints are the sum of its individual components (no spectral cross-talk); (4) near independence of the Raman fingerprint to its physical state (very similar spectra for gas, liquid, solid and solutions -- either bulk or aerosols); and (5) insensitivity of the Raman signature to environmental conditions (no quenching). Data from a few chemicals will be presented which illustrate these features. In cases where background fluorescence accompanies the Raman signals, an effective frequency modulation technique has been developed, which can completely eliminate this interference.

  11. Monitoring and trace detection of hazardous waste and toxic chemicals using resonance Raman spectroscopy

    SciTech Connect

    Sedlacek, A.J. III; Dougherty, D.R.; Chen, C.L.

    1993-04-01

    Raman scattering is a coherent, inelastic, two-photon process, which shifts the frequency of an outgoing photon according to the vibrational structure of the irradiated species, thereby providing a unique fingerprint of the molecule. When involving an allowed electronic transition (resonance Raman), this scattering cross section can be enhanced by 10{sup 4} to 10{sup 6} and provides the basis for a viable technique that can monitor and detect trace quantities of hazardous wastes and toxic chemicals. Resonance Raman spectroscopy (RRS) possesses many of the ideal characteristics for monitoring and detecting of hazardous waste and toxic chemicals. Some of these traits are: (1) very high selectivity (chemical specific fingerprints); (2) independence from the excitation wavelength (ability to monitor in the solar blind region); (3) chemical mixture fingerprints are the sum of its individual components (no spectral cross-talk); (4) near independence of the Raman fingerprint to its physical state (very similar spectra for gas, liquid, solid and solutions -- either bulk or aerosols); and (5) insensitivity of the Raman signature to environmental conditions (no quenching). Data from a few chemicals will be presented which illustrate these features. In cases where background fluorescence accompanies the Raman signals, an effective frequency modulation technique has been developed, which can completely eliminate this interference.

  12. Anaerobic baffled reactor coupled with chemical precipitation for treatment and toxicity reduction of industrial wastewater.

    PubMed

    Laohaprapanona, Sawanya; Marquesa, Marcia; Hogland, William

    2014-01-01

    This study describes the reduction of soluble chemical oxygen demand (CODs) and the removal of dissolved organic carbon (DOC), formaldehyde (FA) and nitrogen from highly polluted wastewater generated during cleaning procedures in wood floor manufacturing using a laboratory-scale biological anaerobic baffled reactor followed by chemical precipitation using MgCI2 .6H20 + Na2HPO4. By increasing the hydraulic retention time from 2.5 to 3.7 and 5 days, the reduction rates of FA, DOC and CODs of nearly 100%, 90% and 83%, respectively, were achieved. When the Mg:N:P molar ratio in the chemical treatment was changed from 1:1:1 to 1.3:1:1.3 at pH 8, the NH4+ removal rate increased from 80% to 98%. Biologically and chemically treated wastewater had no toxic effects on Vibrio fischeri and Artemia salina whereas chemically treated wastewater inhibited germination of Lactuca sativa owing to a high salt content. Regardless of the high conductivity of the treated wastewater, combined biological and chemical treatment was found to be effective for the removal of the organic load and nitrogen, and to be simple to operate and to maintain. A combined process such as that investigated could be useful for on-site treatment of low volumes of highly polluted wastewater generated by the wood floor and wood furniture industries, for which there is no suitable on-site treatment option available today.

  13. Morphological and Chemical Mechanisms of Elongated Mineral Particle Toxicities

    PubMed Central

    Aust, Ann E.; Cook, Philip M.; Dodson, Ronald F.

    2011-01-01

    Much of our understanding regarding the mechanisms for induction of disease following inhalation of respirable elongated mineral particles (REMP) is based on studies involving the biological effects of asbestos fibers. The factors governing the disease potential of an exposure include duration and frequency of exposures; tissue-specific dose over time; impacts on dose persistence from in vivo REMP dissolution, comminution, and clearance; individual susceptibility; and the mineral type and surface characteristics. The mechanisms associated with asbestos particle toxicity involve two facets for each particle's contribution: (1) the physical features of the inhaled REMP, which include width, length, aspect ratio, and effective surface area available for cell contact; and (2) the surface chemical composition and reactivity of the individual fiber/elongated particle. Studies in cell-free systems and with cultured cells suggest an important way in which REMP from asbestos damage cellular molecules or influence cellular processes. This may involve an unfortunate combination of the ability of REMP to chemically generate potentially damaging reactive oxygen species, through surface iron, and the interaction of the unique surfaces with cell membranes to trigger membrane receptor activation. Together these events appear to lead to a cascade of cellular events, including the production of damaging reactive nitrogen species, which may contribute to the disease process. Thus, there is a need to be more cognizant of the potential impact that the total surface area of REMP contributes to the generation of events resulting in pathological changes in biological systems. The information presented has applicability to inhaled dusts, in general, and specifically to respirable elongated mineral particles. PMID:21534085

  14. Toxicity testing of organic chemicals in groundwater polluted with landfill leachate

    SciTech Connect

    Baun, A.; Kloeft, L.; Bjerg, P.L.; Nyholm, N.

    1999-09-01

    A method for assessment of toxicity of nonvolatile organic chemicals contaminants in groundwater polluted with landfill leachate has been evaluated. The biotests utilized were composed of an algal growth inhibition test (Selenastrum capricornutum), a daphnia immobilization test (Daphnia magna), and a bacterial genotoxicity test (umuC, Salmonella typhimurium). The feasibility of the selected biotests was investigated for a series of groundwater samples collected along pollution gradients downstreams of two landfills in Jutland, Denmark. Two different approaches were used, direct toxicity testing of whole groundwater samples, and toxicity testing of concentrates obtained by solid-phase extraction. Direct testing of whole groundwater samples produced toxic responses, but the complex sample matrix masked the toxicity of the organic chemical contaminants of interest. Solid-phase extraction was used successfully as an on-site method that eliminated ion toxicity and produced biotest responses that reflected the toxicity of the nonvolatile organic chemical contaminants in the groundwater.

  15. Modification of the Neubauer technique to assess toxicity of hazardous chemicals in soils

    SciTech Connect

    Thomas, J.M.; Cline, J.F.

    1985-01-01

    The Neubauer technique was modified to provide a sensitive and economical phytoassay for soils and surface waters obtained from a chemical waste site. Use of individual plastic enclosures allowed safe handling and disposal over the course of our experiments. Laboratory tests showed that water from a holding basin was toxic to wheat plants at dilutions of less than 1% and that our modified Neubauer technique produced results compatible with both pot culture and the standard Neubauer test. Further testing of several inorganic constituents of the basin water pointed to an organic toxicant, even though the original water contained high levels of sodium, copper and other elements. The results of testing 26 samples from an abandoned waste pond were negative insofar as toxicity to wheat and lettuce seeds, whereas samples from an abandoned ditch allowed us to determine areal toxicity as well as toxicity as a function of depth and suggested that more than one species should be tested. 10 references, 2 figures, 5 tables.

  16. Low toxicity high temperature PMR polyimide

    NASA Technical Reports Server (NTRS)

    Pater, Ruth H. (Inventor)

    1992-01-01

    In-situ polymerization of monomer reactants (PMR) type polyimides constitute an important class of ultra high performance composite matrix resins. PMR-15 is the best known and most widely used PMR polyimide. An object of the present invention is to provide a substantially improved high temperature PMR-15 system that exhibits better processability, toughness, and thermo-oxidative stability than PMR-15, as well as having a low toxicity. Another object is to provide new PMR polyimides that are useful as adhesives, moldings, and composite matrices. By the present invention, a new PMR polyimide comprises a mixture of the following compounds: 3,4'-oxydianiline (3,4'-ODA), NE, and BTDE which are then treated with heat. This PMR was designated LaRC-RP46 and has a broader processing window, better reproducibility of high quality composite parts, better elevated temperature mechanical properties, and higher retention of mechanical properties at an elevated temperature, particularly, at 371 C.

  17. The inadequacies of pre-market chemical risk assessment's toxicity studies-the implications.

    PubMed

    Tweedale, Anthony C

    2017-01-01

    Industry provides essentially all the data for most (pre-market) chemical risk assessments (RA); academics study a chemical once it is marketed. For two randomly-chosen high production chemicals, despite new European Union mandates to evaluate all data, just 13% of the herbicide bentazon and 15% of the flame-retardant hexabromocyclododecane's published toxicity studies were found in their pre-market RA, and a systematic review on bentazon concludes it has greater hazards than indicated in its RA. More important, for both, academia's toxicity studies were designated as lower quality than industries were, despite showing hazards at lower doses. The accuracy of industry's test methods is analyzed and found to be replicable but insensitive, thus inaccurate. The synthetic pharmaceutical industry originated them, and by 1983 the Organization for Economic Cooperation & Development mandated their test guidelines (TG) methods be accepted for any new study for pre-market RA. For existing studies, industry's "Klimisch" criterion is universally used to evaluate quality, but it only states that TG studies produce the best data. However, no TG can answer the realistic exposure effect hypotheses of academics; therefore, crucially in pre-market RA, tens of thousands of published experimental findings (increasingly at low dose) are ignored to determine the safe dose. Few appreciate this, so scientific debate on the most accurate elements of toxicity tests is urgently indicated. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Export of toxic chemicals - a review of the case of uncontrolled electronic-waste recycling.

    PubMed

    Wong, M H; Wu, S C; Deng, W J; Yu, X Z; Luo, Q; Leung, A O W; Wong, C S C; Luksemburg, W J; Wong, A S

    2007-09-01

    This paper reviews the concentrations of persistent organic pollutants such as flame retardants (PBDEs), dioxins/furans (PCDD/Fs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and heavy metals/metalloid concentrations of different environmental media at Guiyu, a traditional rice-growing village located in southeastern Guangdong Province (PR China), which has turned into an intensive electronic-waste (e-waste) recycling site. Incomplete combustion of e-waste in open air and dumping of processed materials are the major sources of various toxic chemicals. By comparing with existing data available in other areas and also guidelines adopted in different countries, it is obvious that the environment is highly contaminated by these toxic chemicals derived from the recycling processes. For example, the monthly concentration of the sum of 22 PBDE congeners contained in PM(2.5) (16.8ngm(-3)) of air samples at Guiyu was 100 times higher than published data. In order to safeguard the environment and human health, detailed investigations are urgently needed, especially on tracking the exposure pathways of different toxic chemicals which may affect the workers and local residents especially mothers, infants and children.

  19. Toxicity Screening of the ToxCast Chemical Library Using a Zebrafish Developmental Assay

    EPA Science Inventory

    As part of the chemical screening and prioritization research program of the U.S. Environmental Protection Agency, the toxicity of the 320 ToxCast™ Phase I chemicals were assessed using a vertebrate screen of developmental toxicity. Zebrafish embryos/larvae (Danio rerio) were exp...

  20. A Conceptual Framework for Predicting the Toxicity of Reactive Chemicals: Modeling Soft Electrophilicity

    EPA Science Inventory

    Although the literature is replete with QSAR models developed for many toxic effects caused by reversible chemical interactions, the development of QSARs for the toxic effects of reactive chemicals lacks a consistent approach. While limitations exit, an appropriate starting-point...

  1. 40 CFR 372.22 - Covered facilities for toxic chemical release reporting.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Covered facilities for toxic chemical release reporting. 372.22 Section 372.22 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS TOXIC CHEMICAL RELEASE REPORTING: COMMUNITY RIGHT-TO-KNOW...

  2. A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

    EPA Science Inventory

    One of the reported effects for exposure to many of the toxic industrial chemicals is DNA damage. The present study describes a simple, rapid and innovative assay to detect DNA damage resulting from exposure of surrogate DNA to toxic industrial chemicals (acrolein, allylamine, ch...

  3. COMPUTER SUPPORT SYSTEMS FOR ESTIMATING CHEMICAL TOXICITY: PRESENT CAPABILITIES AND FUTURE TRENDS

    EPA Science Inventory

    Computer Support Systems for Estimating Chemical Toxicity: Present Capabilities and Future Trends

    A wide variety of computer-based artificial intelligence (AI) and decision support systems exist currently to aid in the assessment of toxicity for environmental chemicals. T...

  4. COMPUTER SUPPORT SYSTEMS FOR ESTIMATING CHEMICAL TOXICITY: PRESENT CAPABILITIES AND FUTURE TRENDS

    EPA Science Inventory

    Computer Support Systems for Estimating Chemical Toxicity: Present Capabilities and Future Trends

    A wide variety of computer-based artificial intelligence (AI) and decision support systems exist currently to aid in the assessment of toxicity for environmental chemicals. T...

  5. Equity and Information: Information Regulation, Environmental Justice, and Risks from Toxic Chemicals

    ERIC Educational Resources Information Center

    Shapiro, Marc D.

    2005-01-01

    Decreases over time in pounds of industrial chemical emissions have led to concerns that nonminority, higher-income communities have benefited disproportionately in reductions in risk. Toxic chemical release data, modeled for toxicity and dispersion in square kilometer units across 45 states, are used to test six sets of hypotheses of potential…

  6. A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

    EPA Science Inventory

    One of the reported effects for exposure to many of the toxic industrial chemicals is DNA damage. The present study describes a simple, rapid and innovative assay to detect DNA damage resulting from exposure of surrogate DNA to toxic industrial chemicals (acrolein, allylamine, ch...

  7. A Conceptual Framework for Predicting the Toxicity of Reactive Chemicals: Modeling Soft Electrophilicity

    EPA Science Inventory

    Although the literature is replete with QSAR models developed for many toxic effects caused by reversible chemical interactions, the development of QSARs for the toxic effects of reactive chemicals lacks a consistent approach. While limitations exit, an appropriate starting-point...

  8. Equity and Information: Information Regulation, Environmental Justice, and Risks from Toxic Chemicals

    ERIC Educational Resources Information Center

    Shapiro, Marc D.

    2005-01-01

    Decreases over time in pounds of industrial chemical emissions have led to concerns that nonminority, higher-income communities have benefited disproportionately in reductions in risk. Toxic chemical release data, modeled for toxicity and dispersion in square kilometer units across 45 states, are used to test six sets of hypotheses of potential…

  9. Removal of toxic chemicals from water with activated carbon

    USGS Publications Warehouse

    Dawson, V.K.; Marking, L.L.; Bills, T.D.

    1976-01-01

    Activated carbon was effective in removing fish toxicants and anesthetics from water solutions. Its capacity to adsorb 3-trifluoromethyl-4-nitrophenol (TFM), antimycin, NoxfishA? (5% rotenone), Dibrorms, juglone, MSa??222, and benzocaine ranged from 0.1 to 64 mg per gram of carbon. The adsorptive capacity (end point considered as a significant discharge) of activated carbon for removal of TFM was determined at column depths of 15, 30, and 60 cm; temperatures of 7, 12, 17, and 22 C; pH's of 6.5, 7.5, 8.5, and 9.5; and flow rates of 50, 78, 100, 200, and 940 ml/min. Adsorptive capacity increased when the contact time was increased by reducing the flow rate or increasing the column depth. The adsorptive capacity was not significantly influenced by temperature but was substantially higher at pH 6.5 than at the other pH's tested. A practical and efficient filter for purifying chemically treated water was developed.

  10. Prediction of Toxic Pollution Resulting From Warfare Chemical Munitions Dumped In The Sea

    NASA Astrophysics Data System (ADS)

    Korotenko, K. A.

    A 3-D high-resolution Hydrodynamic/Transport model was developed to predict chemical pollution in marine environment with a special reference to warfare chem- icals dumped in the Baltic Sea. The Flow module was developed on the basis of the Princeton Ocean Model (POM). The grid step is chosen at 1/15Deg and 1/30/Deg along x- and y-axes (that is, about 4.0 km and 3.7 km, respectively). The model grid covers the Baltic from 9.3 to 24.6E and from 53.0 to 60.2N. The Transport module of the model takes the predetermined velocity field and uses the random walk technique to predict the motion of individual particles, the sum of which constitutes a consid- ered chemical agent. Several different approaches for modeling are used for different kind of chemical agents. Basic processes affecting the chemicals to be modeled are hydrolysis, solubility, and microbiological destruction. All available toxicity data re- garding the chemical warfare agents of primary concern and the expected degradation products in the Baltic environment were gathered and summarized. This information was used to compare the toxicities of the different agents and their degradation prod- ucts and to decide which chemicals may represent a toxic threat to the environment. The model was adapted to be used for chemical agents with various characteristics and behavior (as Sarin, Lewsite, Musturd, etc.) in seawaters. Special algorithms are developed to describe nonlinear reactions producing toxic and nontoxic products in result of the warfare agent destruction. Sources of chemical pollution in the sea are considered as steady state (chronic) point and/or distributed releases because princi- pally different two methods were used in dumping CW: 1) concentrated dumping of containers, shells, and bombs together with ships; 2) dispersed dumping of individual containers, shells and aircraft bombs from moving vessels. The model was run with four most recurrent climatic wind fields for the Bornholm and Gotland

  11. Evaluating the male and female reproductive toxicity of high-boiling petroleum substances.

    PubMed

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

    2013-11-01

    To meet the EPA HPV Chemical Challenge Program requirement for reproductive toxicity data on sponsored high-boiling petroleum substances (HBPS), an analysis was conducted using the results of 39 repeat-dose and 59 developmental rat dermal toxicity studies on HBPS samples spanning the boiling range of the sponsored substances, and the results of three one-generation reproductive toxicity studies on two samples spanning the concentration range of polycyclic aromatic compounds of sponsored substances. The analysis found little evidence of male or female reproductive tract toxicity based on histopathology, reproductive organ weight, and sperm parameters, and no evidence of effects on fertility, while significant developmental toxicity and/or systemic repeat-dose toxicity were frequently observed. Among 14 samples of HBPS tested in both repeat-dose toxicity and developmental toxicity studies, there were no studies in which an adverse reproductive tract finding occurred at a dose lower than that producing developmental toxicity or other adverse effects in repeat-dose toxicity studies. The current analysis supports the hypothesis that effects in developmental and/or repeat-dose toxicity studies of HBPS occur at doses lower than those that might affect fertility in rat one-generation reproductive studies. When adequate developmental and repeat-dose toxicity studies are available, a reproductive toxicity study of HBPS appears unnecessary.

  12. Computerized in vitro test for chemical toxicity based on tetrahymena swimming patterns

    NASA Technical Reports Server (NTRS)

    Noever, David A.; Matsos, Helen C.; Cronise, Raymond J.; Looger, Loren L.; Relwani, Rachna A.; Johnson, Jacqueline U.

    1994-01-01

    An apparatus and method for rapidly determining chemical toxicity was evaluated. The toxicity monitor includes an automated scoring of how motile biological cells (Tetrahymena pyriformis) slow down or otherwise change their swimming patterns in a hostile chemical environment. The device, called the Motility Assay Apparatus (MAA) is tested for 30 second determination of chemical toxicity in 20 aqueous samples containing trace organics and salts. With equal or better detection limits, results compare favorably to in vivo animal tests of eye irritancy, in addition to agreeing for all chemicals with previous manual evaluations of single cell motility.

  13. Effects of water temperature on the toxicity of chemicals to aquatic organisms

    SciTech Connect

    Mayer, F.; Brecken-Folse, J.; Howe, G.; Linton, T.

    1995-12-31

    Water temperatures fluctuate regularly in aquatic environments, producing physiological and ecological changes in resident biota. Temperature has been recognized as a critical factor affecting the toxicity of chemicals by altering the physiological condition of the biota and the interactions between organisms and toxicants. Temperature significantly affects respiration rates, chemical absorption, and chemical detoxification and excretion. Acute toxicity of most chemicals to aquatic organisms is positively correlated with temperature; however, the toxicity of some chemicals is negatively correlated with or not affected by temperature. Regression slopes of toxicity appear consistent among species within a chemical for temperature, indicating chemical rather than biological differences in toxicity. Temperature may not affect acute toxicity per se, but does affect bioavailability and, therefore, exposure. Octanol/water partition coefficients are altered by temperature and could replace some biological testing since the partition coefficient-acute toxicity relationship has been well established. Temperature may only alter the rate of intoxication in chronic exposures no-effect concentrations do not appear to be affected by temperature; only the time required to attain the same no-effect concentration varies.

  14. Comprehensive assessment of germline chemical toxicity using the nematode Caenorhabditis elegans.

    PubMed

    Parodi, Daniela A; Damoiseaux, Robert; Allard, Patrick

    2015-02-22

    Identifying the reproductive toxicity of the thousands of chemicals present in our environment has been one of the most tantalizing challenges in the field of environmental health. This is due in part to the paucity of model systems that can (1) accurately recapitulate keys features of reproductive processes and (2) do so in a medium- to high-throughput fashion, without the need for a high number of vertebrate animals. We describe here an assay in the nematode C. elegans that allows the rapid identification of germline toxicants by monitoring the induction of aneuploid embryos. By making use of a GFP reporter line, errors in chromosome segregation resulting from germline disruption are easily visualized and quantified by automated fluorescence microscopy. Thus the screening of a particular set of compounds for its toxicity can be performed in a 96- to 384-well plate format in a matter of days. Secondary analysis of positive hits can be performed to determine whether the chromosome abnormalities originated from meiotic disruption or from early embryonic chromosome segregation errors. Altogether, this assay represents a fast first-pass strategy for the rapid assessment of germline dysfunction following chemical exposure.

  15. Chemical-agnostic hazard prediction: statistical inference of in vitro toxicity pathways from proteomics responses to chemical mixtures

    EPA Science Inventory

    Toxicity pathways have been defined as normal cellular pathways that, when sufficiently perturbed as a consequence of chemical exposure, lead to an adverse outcome. If an exposure alters one or more normal biological pathways to an extent that leads to an adverse toxicity outcome...

  16. Antioxidants as potential medical countermeasures for chemical warfare agents and toxic industrial chemicals.

    PubMed

    McElroy, Cameron S; Day, Brian J

    2016-01-15

    The continuing horrors of military conflicts and terrorism often involve the use of chemical warfare agents (CWAs) and toxic industrial chemicals (TICs). Many CWA and TIC exposures are difficult to treat due to the danger they pose to first responders and their rapid onset that can produce death shortly after exposure. While the specific mechanism(s) of toxicity of these agents are diverse, many are associated either directly or indirectly with increased oxidative stress in affected tissues. This has led to the exploration of various antioxidants as potential medical countermeasures for CWA/TIC exposures. Studies have been performed across a wide array of agents, model organisms, exposure systems, and antioxidants, looking at an almost equally diverse set of endpoints. Attempts at treating CWAs/TICs with antioxidants have met with mixed results, ranging from no effect to nearly complete protection. The aim of this commentary is to summarize the literature in each category for evidence of oxidative stress and antioxidant efficacy against CWAs and TICs. While there is great disparity in the data concerning methods, models, and remedies, the outlook on antioxidants as medical countermeasures for CWA/TIC management appears promising.

  17. Insect-gene-activity detection system for chemical and biological warfare agents and toxic industrial chemicals

    NASA Astrophysics Data System (ADS)

    Mackie, Ryan S.; Schilling, Amanda S.; Lopez, Arturo M.; Rayms-Keller, Alfredo

    2002-02-01

    Detection of multiple chemical and biological weapons (CBW) agents and/or complex mixtures of toxic industrial chemicals (TIC) is imperative for both the commercial and military sectors. In a military scenario, a multi-CBW attack would create confusion, thereby delaying decontamination and therapeutic efforts. In the commercial sector, polluted sites invariably contain a mixture of TIC. Novel detection systems capable of detecting CBW and TIC are sorely needed. While it may be impossible to build a detector capable of discriminating all the possible combinations of CBW, a detection system capable of statistically predicting the most likely composition of a given mixture is within the reach of current emerging technologies. Aquatic insect-gene activity may prove to be a sensitive, discriminating, and elegant paradigm for the detection of CBW and TIC. We propose to systematically establish the expression patterns of selected protein markers in insects exposed to specific mixtures of chemical and biological warfare agents to generate a library of biosignatures of exposure. The predicting capabilities of an operational library of biosignatures of exposures will allow the detection of emerging novel or genetically engineered agents, as well as complex mixtures of chemical and biological weapons agents. CBW and TIC are discussed in the context of war, terrorism, and pollution.

  18. Sensitive detection of chemical agents and toxic industrial chemicals using active open-path FTIRs

    NASA Astrophysics Data System (ADS)

    Walter, William T.

    2004-03-01

    Active open-path FTIR sensors provide more sensitive detection of chemical agents than passive FTIRs, such as the M21 RSCAAL and JSLSCAD, and at the same time identify and quantify toxic industrial chemicals (TIC). Passive FTIRs are bistatic sensors relying on infrared sources of opportunity. Utilization of earth-based sources of opportunity limits the source temperatures available for passive chemical-agent FTIR sensors to 300° K. Active FTIR chemical-agent sensors utilize silicon carbide sources, which can be operated at 1500° K. The higher source temperature provides more than an 80-times increase in the infrared radiant flux emitted per unit area in the 7 to 14 micron spectral fingerprint region. Minimum detection limits are better than 5 μgm/m3 for GA, GB, GD, GF and VX. Active FTIR sensors can (1) assist first responders and emergency response teams in their assessment of and reaction to a terrorist threat, (2) provide information on the identification of the TIC present and their concentrations and (3) contribute to the understanding and prevention of debilitating disorders analogous to the Gulf War Syndrome for military and civilian personnel.

  19. Monitoring toxicity of industrial wastewater and specific chemicals to a green alga, nitrifying bacteria and an aquatic bacterium.

    PubMed

    Eilersen, A M; Arvin, E; Henze, M

    2004-01-01

    Treatment plants may be exposed to a whole range of toxic organic and inorganic compounds that may inhibit the removal of organic matter and nitrogen. In order to secure maximum treatment efficiency, the plant manager has to monitor the toxicity of the influent sewage. With regard to the receiving water the manager also has to make sure that toxicity in the influent is significantly reduced during treatment. Because a whole range of chemicals may be present, chemical analysis may be insufficient and expensive as a control instrument. Instead, direct toxicity measurements are preferable to capture the complexity of the wastewater. The monitoring methods have to be relevant and sensitive for the processes in the treatment plant, i.e. removal of organic matter and nutrients. The methods also have to be simple and inexpensive. The paper reports on recent results from the application of nitrification, algae and Biotox tests, and summarises the experience with monitoring of toxicity. Although the sensitivity of the tests varies with respect to individual chemicals or group of chemicals, the application of a combination of the tests gives a high likelihood of detecting toxic impacts on treatment plants and receiving waters.

  20. Temperature-dependent toxicities of four common chemical pollutants to the marine medaka fish, copepod and rotifer.

    PubMed

    Li, Adela J; Leung, Priscilla T Y; Bao, Vivien W W; Yi, Andy X L; Leung, Kenneth M Y

    2014-10-01

    We hypothesize that chemical toxicity to marine ectotherms is the lowest at an optimum temperature (OT) and it exacerbates with increasing or decreasing temperature from the OT. This study aimed to verify this hypothetical temperature-dependent chemical toxicity (TDCT) model through laboratory experiments. Acute toxicity over a range of temperatures was tested on four commonly used chemicals to three marine ectotherms. Our results confirmed that toxicities, in terms of 96-h LC50 (median lethal concentration; for the marine medaka fish Oryzias melastigma and the copepod Tigriopus japonicus) and 24-h LC50 (for the rotifer Brachionus koreanus), were highly temperature-dependent, and varied between test species and between study chemicals. The LC50 value of the fish peaked at 20 °C for copper (II) sulphate pentahydrate and triphenyltin chloride, and at 25 °C for dichlorophenyltrichloroethane and copper pyrithione, and decreased with temperature increase or decrease from the peak (i.e., OT). However, LC50 values of the copepod and the rotifer generally showed a negative relationship with temperature across all test chemicals. Both copepod and rotifer entered dormancy at the lowest temperature of 4 °C. Such metabolic depression responses in these zooplanktons could reduce their uptake of the chemical and hence minimize the chemical toxicity at low temperatures. Our TDCT model is supported by the fish data only, whereas a simple linear model fits better to the zooplankton data. Such species-specific TDCT patterns may be jointly ascribed to temperature-mediated changes in (1) the physiological response and susceptibility of the marine ectotherms to the chemical, (2) speciation and bioavailability of the chemical, and (3) toxicokinetics of the chemical in the organisms.

  1. Estimating the Potential Toxicity of Chemicals Associated with Hydraulic Fracturing Operations Using Quantitative Structure-Activity Relationship Modeling.

    PubMed

    Yost, Erin E; Stanek, John; DeWoskin, Robert S; Burgoon, Lyle D

    2016-07-19

    The United States Environmental Protection Agency (EPA) identified 1173 chemicals associated with hydraulic fracturing fluids, flowback, or produced water, of which 1026 (87%) lack chronic oral toxicity values for human health assessments. To facilitate the ranking and prioritization of chemicals that lack toxicity values, it may be useful to employ toxicity estimates from quantitative structure-activity relationship (QSAR) models. Here we describe an approach for applying the results of a QSAR model from the TOPKAT program suite, which provides estimates of the rat chronic oral lowest-observed-adverse-effect level (LOAEL). Of the 1173 chemicals, TOPKAT was able to generate LOAEL estimates for 515 (44%). To address the uncertainty associated with these estimates, we assigned qualitative confidence scores (high, medium, or low) to each TOPKAT LOAEL estimate, and found 481 to be high-confidence. For 48 chemicals that had both a high-confidence TOPKAT LOAEL estimate and a chronic oral reference dose from EPA's Integrated Risk Information System (IRIS) database, Spearman rank correlation identified 68% agreement between the two values (permutation p-value =1 × 10(-11)). These results provide support for the use of TOPKAT LOAEL estimates in identifying and prioritizing potentially hazardous chemicals. High-confidence TOPKAT LOAEL estimates were available for 389 of 1026 hydraulic fracturing-related chemicals that lack chronic oral RfVs and OSFs from EPA-identified sources, including a subset of chemicals that are frequently used in hydraulic fracturing fluids.

  2. Acute toxicity of Daphnia pulex to six classes of chemical compounds potentially hazardous to Great Lakes aquatic biota

    USGS Publications Warehouse

    Smith, Stephen B.; Savino, Jacqueline F.; Blouin, Marc A.

    1988-01-01

    Of the six classes of chemicals potentially hazardous to Great Lakes aquatic biota, derivatives of polyaromatic hydrocarbons (PAHs) were the most acutely toxic (48-h EC 50) to Daphnia pulex. The other classes, listed in order of decreasing toxicity were alkyl halides, nitrogen-containing compounds, cyclic alkanes, heterocyclic nitrogen compounds, silicon-containing compounds. O f the 41 compounds representing the six chemical classes, 6 were extremely toxic (> 0.01 - 0.1 mg/L), 11 highly toxic (> 01. - 1.0 mg/L), 20 moderately toxic (> 1.0 - 10.0 mg/L), and 4 slightly toxic (>10 - 100 mg/L). The reference compound, p, p'DDT, was super toxic (< 0.01 mg/L). Based on toxicity and relative abundance (hazard ranking) of the 21 compounds that were detected in tissue of Great Lakes fishes, the classes of compounds that present the greatest threat to Great Lakes aquatic biota are PAH derivatives, alkyl halides, and cyclic aklanes.

  3. Predictive Model of Rat Reproductive Toxicity from ToxCast High Throughput Screening

    EPA Science Inventory

    The EPA ToxCast research program uses high throughput screening for bioactivity profiling and predicting the toxicity of large numbers of chemicals. ToxCast Phase‐I tested 309 well‐characterized chemicals in over 500 assays for a wide range of molecular targets and cellular respo...

  4. Predictive Model of Rat Reproductive Toxicity from ToxCast High Throughput Screening

    EPA Science Inventory

    The EPA ToxCast research program uses high throughput screening for bioactivity profiling and predicting the toxicity of large numbers of chemicals. ToxCast Phase‐I tested 309 well‐characterized chemicals in over 500 assays for a wide range of molecular targets and cellular respo...

  5. In silico toxicology: computational methods for the prediction of chemical toxicity.

    PubMed

    Raies, Arwa B; Bajic, Vladimir B

    2016-03-01

    Determining the toxicity of chemicals is necessary to identify their harmful effects on humans, animals, plants, or the environment. It is also one of the main steps in drug design. Animal models have been used for a long time for toxicity testing. However, in vivo animal tests are constrained by time, ethical considerations, and financial burden. Therefore, computational methods for estimating the toxicity of chemicals are considered useful. In silico toxicology is one type of toxicity assessment that uses computational methods to analyze, simulate, visualize, or predict the toxicity of chemicals. In silico toxicology aims to complement existing toxicity tests to predict toxicity, prioritize chemicals, guide toxicity tests, and minimize late-stage failures in drugs design. There are various methods for generating models to predict toxicity endpoints. We provide a comprehensive overview, explain, and compare the strengths and weaknesses of the existing modeling methods and algorithms for toxicity prediction with a particular (but not exclusive) emphasis on computational tools that can implement these methods and refer to expert systems that deploy the prediction models. Finally, we briefly review a number of new research directions in in silico toxicology and provide recommendations for designing in silico models. WIREs Comput Mol Sci 2016, 6:147-172. doi: 10.1002/wcms.1240 For further resources related to this article, please visit the WIREs website.

  6. Predicting Michael-acceptor reactivity and toxicity through quantum chemical transition-state calculations.

    PubMed

    Mulliner, Denis; Wondrousch, Dominik; Schüürmann, Gerrit

    2011-12-21

    The electrophilic reactivity of Michael acceptors is an important determinant of their toxicity. For a set of 35 α,β-unsaturated aldehydes, ketones and esters with experimental rate constants of their reaction with glutathione (GSH), k(GSH), quantum chemical transition-state calculations of the corresponding Michael addition of the model nucleophile methane thiol (CH(3)SH) have been performed at the B3LYP/6-31G** level, focusing on the 1,2-olefin addition pathway without and with initial protonation. Inclusion of Boltzmann-weighting of conformational flexibility yields intrinsic reaction barriers ΔE(‡) that for the case of initial protonation correctly reflect the structural variation of k(GSH) across all three compound classes, except that they fail to account for a systematic (essentially incremental) decrease in reactivity upon α-substitution. By contrast, the reduction in k(GSH) through β-substitution is well captured by ΔE(‡). Empirical correction for the α-substitution effect yields a high squared correlation coefficient (r(2) = 0.96) for the quantum chemical prediction of log k(GSH), thus enabling an in silico screening of the toxicity-relevant electrophilicity of α,β-unsaturated carbonyls. The latter is demonstrated through application of the calculation scheme for a larger set of 46 Michael-acceptor aldehydes, ketones and esters with experimental values for their toxicity toward the ciliates Tetrahymena pyriformis in terms of 50% growth inhibition values after 48 h exposure (EC(50)). The developed approach may add in the predictive hazard evaluation of α,β-unsaturated carbonyls such as for the European REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) Directive, enabling in particular an early identification of toxicity-relevant Michael-acceptor reactivity.

  7. Evaluating the aquatic toxicity of complex organic chemical mixtures: lessons learned from polycyclic aromatic hydrocarbon and petroleum hydrocarbon case studies.

    PubMed

    Landrum, Peter F; Chapman, Peter M; Neff, Jerry; Page, David S

    2012-04-01

    Experimental designs for evaluating complex mixture toxicity in aquatic environments can be highly variable and, if not appropriate, can produce and have produced data that are difficult or impossible to interpret accurately. We build on and synthesize recent critical reviews of mixture toxicity using lessons learned from 4 case studies, ranging from binary to more complex mixtures of primarily polycyclic aromatic hydrocarbons and petroleum hydrocarbons, to provide guidance for evaluating the aquatic toxicity of complex mixtures of organic chemicals. Two fundamental requirements include establishing a dose-response relationship and determining the causative agent (or agents) of any observed toxicity. Meeting these 2 requirements involves ensuring appropriate exposure conditions and measurement endpoints, considering modifying factors (e.g., test conditions, test organism life stages and feeding behavior, chemical transformations, mixture dilutions, sorbing phases), and correctly interpreting dose-response relationships. Specific recommendations are provided. Copyright © 2011 SETAC.

  8. Primary chemical and physical characterization of acute toxic components in wastewaters

    SciTech Connect

    Svenson, A.; Linlin, Z.; Kaj, L. )

    1992-10-01

    A chemical and physical primary characterization work sheet was developed based on the Microtox test, a bacterial bioluminescence system used as a rapid estimate of acute aquatic toxic effects. Measurements of the variation in light reduction upon different pretreatments provided information about the chemical and physical properties of the main toxic component(s) in test wastewater samples. This primary characterization of a wastewater sample was performed within 1 day. Tests of pure toxic chemical compounds and wastewaters with known and unknown primary toxicants are presented. Outlines to the chemical analysis and identification of toxic components may be deduced from the primary characterization. The provisional characterization may also provide information on wastewater treatment techniques.

  9. The relationship between the toxicity and structure of nitroaromatic chemicals

    SciTech Connect

    Bailey, M.C.; Spanggord, R.J.

    1981-10-01

    The acute toxicities of nitrotoluene, dinitrotoluene, trinitrotoluene, aminonitrotoluene, aminodinitrotoluene, and dinitrobenzene isomers were evaluated in fathead minnows. For the nitroaromatics, toxicity appeared to be related to the number and orientation of nitro groups; compounds with nitro groups positioned ortho or para to each other were appreciably more toxic than isomers having the nitro groups in the meta orientation. In contrast, the toxicities of the aminonitrotoluenes and aminodinitrotoluenes were not related in any obvious way to their structures. Two mechanisms may account for the differences in toxicity between the nitroaromatic isomers: nucleophilic displacement of a nitro group and reduction of a nitro group. The available data indicate that reduction of a nitro group is the more likely pathway.

  10. Genetic and Biochemical Analysis of High Iron Toxicity in Yeast

    PubMed Central

    Lin, Huilan; Li, Liangtao; Jia, Xuan; Ward, Diane McVey; Kaplan, Jerry

    2011-01-01

    Iron storage in yeast requires the activity of the vacuolar iron transporter Ccc1. Yeast with an intact CCC1 are resistant to iron toxicity, but deletion of CCC1 renders yeast susceptible to iron toxicity. We used genetic and biochemical analysis to identify suppressors of high iron toxicity in Δccc1 cells to probe the mechanism of high iron toxicity. All genes identified as suppressors of high iron toxicity in aerobically grown Δccc1 cells encode organelle iron transporters including mitochondrial iron transporters MRS3, MRS4, and RIM2. Overexpression of MRS3 suppressed high iron toxicity by decreasing cytosolic iron through mitochondrial iron accumulation. Under anaerobic conditions, Δccc1 cells were still sensitive to high iron toxicity, but overexpression of MRS3 did not suppress iron toxicity and did not result in mitochondrial iron accumulation. We conclude that Mrs3/Mrs4 can sequester iron within mitochondria under aerobic conditions but not anaerobic conditions. We show that iron toxicity in Δccc1 cells occurred under both aerobic and anaerobic conditions. Microarray analysis showed no evidence of oxidative damage under anaerobic conditions, suggesting that iron toxicity may not be solely due to oxidative damage. Deletion of TSA1, which encodes a peroxiredoxin, exacerbated iron toxicity in Δccc1 cells under both aerobic and anaerobic conditions, suggesting a unique role for Tsa1 in iron toxicity. PMID:21115478

  11. Toxicological characteristics of endocrine-disrupting chemicals: developmental toxicity, carcinogenicity, and mutagenicity.

    PubMed

    Choi, Seul Min; Yoo, Sun Dong; Lee, Byung Mu

    2004-01-01

    It is generally accepted that endocrine-disrupting chemicals (EDCs) play a role in a variety of adverse health effects in an intact organism or its progeny as a consequence of changes in the endocrine system. Primary toxic effects of EDCs were reported to be related to infertility, reduction in sperm count, and teratogenicity, but other important toxic effects of EDCs such as carcinogenicity and mutagenicity have also been demonstrated. The aim of the present study was to systematically analyze the toxicological characteristics of EDCs in pesticides, industrial chemicals, and metals. A comprehensive literature survey on the 48 EDCs classified by the Centers for Disease Control and Prevention (CDC) was conducted using a number of databases which included Medline, Toxline, and Toxnet. The survey results revealed that toxicological characteristics of EDCs were shown to produce developmental toxicity (81%), carcinogenicity (79%, when positive in at least one animal species; 48%, when classified based on IARC evaluation), mutagenicity (79%), immunotoxicity (52%), and neurotoxicity (50%). Regarding the hormone-modulating effects of the 48 EDCs, estrogenic effects were the most predominant in pesticides, while effects on thyroid hormone were found for heavy metals. EDCs showing estrogen-modulating effects were closely related to carcinogenicity or mutagenicity with a high degree of sensitivity. Systematic information on the toxicological characteristics of the EDCs will be useful for future research directions on EDCs, the development of new screening methods, legal regulation, and for investigations of their mechanism of action.

  12. High energy chemical laser system

    DOEpatents

    Gregg, D.W.; Pearson, R.K.

    1975-12-23

    A high energy chemical laser system is described wherein explosive gaseous mixtures of a reducing agent providing hydrogen isotopes and interhalogen compounds are uniformly ignited by means of an electrical discharge, flash- photolysis or an electron beam. The resulting chemical explosion pumps a lasing chemical species, hydrogen fluoride or deuterium fluoride which is formed in the chemical reaction. The generated lasing pulse has light frequencies in the 3- micron range. Suitable interhalogen compounds include bromine trifluoride (BrF$sub 3$), bromine pentafluoride (BrF$sub 5$), chlorine monofluoride (ClF), chlorine trifluoride (ClF$sub 3$), chlorine pentafluoride (ClF$sub 5$), iodine pentafluoride (IF$sub 5$), and iodine heptafluoride (IF$sub 7$); and suitable reducing agents include hydrogen (H$sub 2$), hydrocarbons such as methane (CH$sub 4$), deuterium (D$sub 2$), and diborane (B$sub 2$H$sub 6$), as well as combinations of the gaseous compound and/or molecular mixtures of the reducing agent.

  13. Chemicals in the environment and developmental toxicity to children: a public health and policy perspective.

    PubMed

    Goldman, L R; Koduru, S

    2000-06-01

    There are numerous pesticides and toxic chemicals in the environment that have yet to be evaluated for potential to cause developmental neurotoxicity. Recent legislation and testing initiatives provide an impetus to generating more information about potential hazards to children. In the United States, the 1996 Food Quality Protection Act (FQPA) required the U.S. Environmental Protection Agency (U.S. EPA) to make a finding that a pesticide food use is safe for children. In addition, the law requires U.S. EPA to incorporate an additional 10-fold factor in risk assessments for pesticide residue tolerances to take into account the special sensitivities of infants and children as well as incomplete data with respect to toxicity and exposures. The potential of chemicals in food and drinking water to cause endocrine disruption will also be examined via the Endocrine Disruptor Screening and Testing Program required by the FQPA and the 1996 Safe Drinking Water Act. In addition, a new voluntary chemical information program will provide screening-level information for the some 2,800 high-volume chemicals in commerce in the United States. These initiatives will need to be accompanied by research focused on developmental toxicity for children, including developmental disabilities. Developmental disabilities exact a large toll on children's health in the United States. Three major developmental disabilities--autism, cerebral palsy, and severe mental retardation--each affect substantial numbers of children. We know very little about the etiology of these conditions. A number of priority areas for research are suggested, including a large environmental prospective study of developmental neurotoxicity.

  14. TOXICOGENOMIC STUDY OF TRIAZOLE FUNGICIDES AND PERFLUOROALKYL ACIDS IN RAT LIVERS ACCURATELY CATEGORIZES CHEMICALS AND IDENTIFIES MECHANISMS OF TOXICITY

    EPA Science Inventory

    Toxicogenomic analysis of five environmental chemicals was performed to investigate the ability of genomics to predict toxicity, categorize chemicals, and elucidate mechanisms of toxicity. Three triazole antifungals (myclobutanil, propiconazole, and triadimefon) and two perfluori...

  15. TOXICOGENOMIC STUDY OF TRIAZOLE FUNGICIDES AND PERFLUOROALKYL ACIDS IN RAT LIVERS ACCURATELY CATEGORIZES CHEMICALS AND IDENTIFIES MECHANISMS OF TOXICITY

    EPA Science Inventory

    Toxicogenomic analysis of five environmental chemicals was performed to investigate the ability of genomics to predict toxicity, categorize chemicals, and elucidate mechanisms of toxicity. Three triazole antifungals (myclobutanil, propiconazole, and triadimefon) and two perfluori...

  16. Estimating the Potential Toxicity of Chemicals Associated with Hydraulic Fracturing Operations Using Quantitative Structure-Activity Relationship Modeling

    EPA Pesticide Factsheets

    Researchers facilitated evaluation of chemicals that lack chronic oral toxicity values using a QSAR model to develop estimates of potential toxicity for chemicals used in HF fluids or found in flowback or produced water

  17. Molecular toxicity identification evaluation (mTIE) approach predicts chemical exposure in Daphnia magna.

    PubMed

    Antczak, Philipp; Jo, Hun Je; Woo, Seonock; Scanlan, Leona; Poynton, Helen; Loguinov, Alex; Chan, Sarah; Falciani, Francesco; Vulpe, Chris

    2013-10-15

    Daphnia magna is a bioindicator organism accepted by several international water quality regulatory agencies. Current approaches for assessment of water quality rely on acute and chronic toxicity that provide no insight into the cause of toxicity. Recently, molecular approaches, such as genome wide gene expression responses, are enabling an alternative mechanism based approach to toxicity assessment. While these genomic methods are providing important mechanistic insight into toxicity, statistically robust prediction systems that allow the identification of chemical contaminants from the molecular response to exposure are needed. Here we apply advanced machine learning approaches to develop predictive models of contaminant exposure using a D. magna gene expression data set for 36 chemical exposures. We demonstrate here that we can discriminate between chemicals belonging to different chemical classes including endocrine disruptors and inorganic and organic chemicals based on gene expression. We also show that predictive models based on indices of whole pathway transcriptional activity can achieve comparable results while facilitating biological interpretability.

  18. Passive dosing of soil invertebrates with polycyclic aromatic hydrocarbons: limited chemical activity explains toxicity cutoff.

    PubMed

    Mayer, Philipp; Holmstrup, Martin

    2008-10-01

    The partitioning of organic soil pollutants into soil organisms is driven by their chemical activity, which normally does not exceed that of the pure pollutant. Passive dosing with the silicone poly(dimethylsiloxane) (PDMS) was used to initiate and maintain the maximum chemical activity of 10 polycyclic aromatic hydrocarbons (PAHs) in toxicity tests with the springtail Folsomia candida. The test animals could move freely on the PDMS saturated with PAHs, resulting in direct contact and exposure to saturated air. After 7 days, springtail lethality correlated neither with the octanol-water partition coefficients of the PAHs nor with their molecular size, but with their melting point All low-melting PAHs (T(M) < or = 110 degrees C) caused 100% lethality, whereas all high-melting PAHs (TM > or = 180 degrees C) caused no significant lethality. The lethality was successfully fitted to one chemical activity response curve for all PAHs tested, with effective chemical activity causing 50% lethality (Ea-50) of 0.058. It was also fitted to the PAH concentration in the PDMS, resulting in an EC(PDMS)-50 of 8.7 mM. Finally, the combined exposure to anthracene and pyrene was described by the sum of chemical activities causing lethality, in good agreement with the chemical activity-response curve obtained.

  19. 2008 Toxic Chemical Release Inventory 2008 Toxic Chemical Release Inventory Community Right-to-Know Act of 1986, Title III, Section 313

    SciTech Connect

    Ecology and Air Quality Group

    2009-10-01

    For reporting year 2008, Los Alamos National Laboratory (LANL) submitted a Form R report for lead as required under the Emergency Planning and Community Right-to- Know Act (EPCRA) Section 313. No other EPCRA Section 313 chemicals were used in 2008 above the reportable thresholds. This document was prepared to provide a description of the evaluation of EPCRA Section 313 chemical use and threshold determinations for LANL for calendar year 2008, as well as to provide background information about data included on the Form R reports. Section 313 of EPCRA specifically requires facilities to submit a Toxic Chemical Release Inventory Report (Form R) to the U.S. Environmental Protection Agency (EPA) and state agencies if the owners and operators manufacture, process, or otherwise use any of the listed toxic chemicals above listed threshold quantities. EPA compiles this data in the Toxic Release Inventory database. Form R reports for each chemical over threshold quantities must be submitted on or before July 1 each year and must cover activities that occurred at the facility during the previous year. In 1999, EPA promulgated a final rule on persistent bioaccumulative toxics (PBTs). This rule added several chemicals to the EPCRA Section 313 list of toxic chemicals and established lower reporting thresholds for these and other PBT chemicals that were already reportable. These lower thresholds became applicable in reporting year 2000. In 2001, EPA expanded the PBT rule to include a lower reporting threshold for lead and lead compounds. Facilities that manufacture, process, or otherwise use more than 100 lb of lead or lead compounds must submit a Form R.

  20. Computerized In Vitro Test for Chemical Toxicity Based on Tetrahymena Swimming Patterns

    NASA Technical Reports Server (NTRS)

    Noever, David A.; Matsos, Helen C.; Cronise, Raymond J.; Looger, Loren L.; Relwani, Rachna A.; Johnson, Jacqueline U.

    1994-01-01

    An apparatus and a method for rapidly determining chemical toxicity have been evaluated as an alternative to the rabbit eye initancy test (Draize). The toxicity monitor includes an automated scoring of how motile biological cells (Tetrahymena pyriformis) slow down or otherwise change their swimming patterns in a hostile chemical environment. The method, called the motility assay (MA), is tested for 30 s to determine the chemical toxicity in 20 aqueous samples containing trace organics and salts. With equal or better detection limits, results compare favorably to in vivo animal tests of eye irritancy.

  1. Anaerobic toxicity and biodegradability of hydrolysis products of chemical warfare agents.

    PubMed

    Sklyar, V I; Mosolova, T P; Kucherenko, I A; Degtyarova, N N; Varfolomeyev, S D; Kalyuzhnyi, S V

    1999-08-01

    The toxicity and biodegradability of the main hydrolysis products of chemical warfare agents were investigated under methanogenic conditions. Among the tested substances, only MPhA does not have any toxic effect with regard to the aceticlastic methanogenic activity. The toxicity of other compounds varied between moderate (TDG, mercaptoethanol) to strong (ethanolamine, diisobutyl ester of MPhA). Biodegradability tests showed that all the products of chemical detoxification of mustard gas (ethanolamine, ethylene glycol, TDG, mercaptoethanol) can be biomineralized under methanogenic conditions. On the contrary, phosphorus-containing compounds from the chemical detoxification of nerve warfare agents (Sarin, Soman, Vx-gases) are quite persistent under these conditions.

  2. 76 FR 38169 - Toxic Substances Control Act Chemical Testing; Receipt of Test Data

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-29

    ...This notice announces EPA's receipt of test data on five chemicals listed in the Toxic Substances Control Act (TSCA) section 4 test rule titled ``In Vitro Dermal Absorption Rate Testing of Certain Chemicals of Interest to the Occupational Safety and Health Administration,'' amended by the final rule titled ``Revocation of the TSCA Section 4 Testing Requirements for Certain Chemical Substances.''

  3. Picking Cell Lines for High-Throughput Transcriptomic Toxicity ...

    EPA Pesticide Factsheets

    High throughput, whole genome transcriptomic profiling is a promising approach to comprehensively evaluate chemicals for potential biological effects. To be useful for in vitro toxicity screening, gene expression must be quantified in a set of representative cell types that captures the diversity of potential responses across chemicals. The ideal dataset to select these cell types would consist of hundreds of cell types treated with thousands of chemicals, but does not yet exist. However, basal gene expression data may be useful as a surrogate for representing the relevant biological space necessary for cell type selection. The goal of this study was to identify a small (< 20) number of cell types that capture a large, quantifiable fraction of basal gene expression diversity. Three publicly available collections of Affymetrix U133+2.0 cellular gene expression data were used: 1) 59 cell lines from the NCI60 set; 2) 303 primary cell types from the Mabbott et al (2013) expression atlas; and 3) 1036 cell lines from the Cancer Cell Line Encyclopedia. The data were RMA normalized, log-transformed, and the probe sets mapped to HUGO gene identifiers. The results showed that <20 cell lines capture only a small fraction of the total diversity in basal gene expression when evaluated using either the entire set of 20960 HUGO genes or a subset of druggable genes likely to be chemical targets. The fraction of the total gene expression variation explained was consistent when

  4. Predictive Modeling of Chemical Hazard by Integrating Numerical Descriptors of Chemical Structures and Short-term Toxicity Assay Data

    PubMed Central

    Rusyn, Ivan; Sedykh, Alexander; Guyton, Kathryn Z.; Tropsha, Alexander

    2012-01-01

    Quantitative structure-activity relationship (QSAR) models are widely used for in silico prediction of in vivo toxicity of drug candidates or environmental chemicals, adding value to candidate selection in drug development or in a search for less hazardous and more sustainable alternatives for chemicals in commerce. The development of traditional QSAR models is enabled by numerical descriptors representing the inherent chemical properties that can be easily defined for any number of molecules; however, traditional QSAR models often have limited predictive power due to the lack of data and complexity of in vivo endpoints. Although it has been indeed difficult to obtain experimentally derived toxicity data on a large number of chemicals in the past, the results of quantitative in vitro screening of thousands of environmental chemicals in hundreds of experimental systems are now available and continue to accumulate. In addition, publicly accessible toxicogenomics data collected on hundreds of chemicals provide another dimension of molecular information that is potentially useful for predictive toxicity modeling. These new characteristics of molecular bioactivity arising from short-term biological assays, i.e., in vitro screening and/or in vivo toxicogenomics data can now be exploited in combination with chemical structural information to generate hybrid QSAR–like quantitative models to predict human toxicity and carcinogenicity. Using several case studies, we illustrate the benefits of a hybrid modeling approach, namely improvements in the accuracy of models, enhanced interpretation of the most predictive features, and expanded applicability domain for wider chemical space coverage. PMID:22387746

  5. A Novel Water Delivery System for Administering Volatile Chemicals while Minimizing Chemical Waste in Rodent Toxicity Studies

    EPA Science Inventory

    Rodent toxicity studies typically use water bottles to administer test chemicals via drinking water. However, water bottles provide inconsistent exposure of volatile chemicals due to varying headspace, as well as lead to excessive waste of test material. In order to refine drin...

  6. A novel water delivery system for administering volatile chemicals while minimizing chemical waste in rodent toxicity sutdies

    EPA Science Inventory

    Rodent toxicity studies typically use water bottles to administer test chemicals via drinking water. However, water bottles provide inconsistent exposure of volatile chemicals due to varying headspace, as well as lead to excessive waste of test material. In order to refine drinki...

  7. A novel water delivery system for administering volatile chemicals while minimizing chemical waste in rodent toxicity sutdies

    EPA Science Inventory

    Rodent toxicity studies typically use water bottles to administer test chemicals via drinking water. However, water bottles provide inconsistent exposure of volatile chemicals due to varying headspace, as well as lead to excessive waste of test material. In order to refine drinki...

  8. A Novel Water Delivery System for Administering Volatile Chemicals while Minimizing Chemical Waste in Rodent Toxicity Studies

    EPA Science Inventory

    Rodent toxicity studies typically use water bottles to administer test chemicals via drinking water. However, water bottles provide inconsistent exposure of volatile chemicals due to varying headspace, as well as lead to excessive waste of test material. In order to refine drin...

  9. Uptake and toxicity of polycyclic aromatic hydrocarbons in terrestrial springtails--studying bioconcentration kinetics and linking toxicity to chemical activity.

    PubMed

    Schmidt, Stine Nørgaard; Smith, Kilian Eric Christopher; Holmstrup, Martin; Mayer, Philipp

    2013-02-01

    Passive dosing applies a polymer loaded with test compound(s) to establish and maintain constant exposure in laboratory experiments. Passive dosing with the silicone poly(dimethylsiloxane) was used to control exposure of the terrestrial springtail Folsomia candida to six polycyclic aromatic hydrocarbons (PAHs) in bioconcentration and toxicity experiments. Folsomia candida could move freely on the PAH-loaded silicone, resulting in exposure via air and direct contact. The bioconcentration kinetics indicated efficient uptake of naphthalene, anthracene, and pyrene through air and (near) equilibrium partitioning of these PAHs to lipids and possibly the waxy layer of the springtail cuticle. Toxicities of naphthalene, phenanthrene, and pyrene were related to chemical activity, which quantifies the energetic level and drives spontaneous processes including diffusive biouptake. Chemical activity-response relationships yielded effective lethal chemical activities (La50s) well within the expected range for baseline toxicity (0.01-0.1). Effective lethal body burdens for naphthalene and pyrene exceeded the expected range of 2 to 8 mmol kg(-1) fresh weight, which again indicated the waxy layer to be a sorbing phase. Finally, chemical activities were converted into equilibrium partitioning concentrations in lipids yielding effective lethal concentrations for naphthalene and phenanthrene in good correspondence with the lethal membrane burden for baseline toxicity (40-160 mmol kg(-1) lipid). Passive dosing was a practical approach for tightly controlling PAH exposure, which in turn provided new experimental possibilities and findings.

  10. Neuroprotective effects of imidazenil against chemical warfare nerve agent soman toxicity in guinea pigs.

    PubMed

    Wang, Ying; Oguntayo, Samuel; Wei, Yanling; Wood, Elisa; Brown, Ammon; Jensen, Neil; Auta, James; Guiodotti, Alessandro; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2012-03-01

    The chemical warfare nerve agent, soman irreversibly inhibits acetylcholinesterase (AChE) leading to hypercholinergy and seizures which trigger glutamate toxicity and status epilepticus ultimately resulting in neuropathology and neurobehavioral deficits. The standard emergency treatment comprising of anticholinergic, AChE reactivator and anticonvulsant does not completely protect against soman toxicity. We have evaluated imidazenil, a new anticonvulsant imidazo benzodiazepine with high affinity and intrinsic efficacy at α5-, α2-, and α3- but low intrinsic efficacy at α1-containing GABA(A) receptors and is devoid of cardiorespiratory depression, sedative/hypnoitc and amnestic actions and does not elicit tolerance and dependence liabilities unlike diazepam, for protection against soman toxicity. Guinea pigs implanted with bipotential radiotelemetry probes for recording EEG and ECG were administered with 26 μg/kg pyridostigmine bromide 30 min prior to 2× LD(50) soman exposure and 1 min later treated with a combination of 2mg/kg atropine sulfate and 25mg/kg 2-pralidoxime and various doses of imidazenil. Intramuscular administration of imidazenil, dose-dependently protected against 2× LD(50) of soman toxicity up to 1mg/kg. Further increase in the dose of imidazenil to 2.5mg/kg was less effective than 1mg/kg probably due to non-specific actions at sites other than GABA(A) receptors. Compared to vehicle group, 1mg/kg imidazenil treatment showed optimal increase in survival rate, reduction in behavioral manifestations and high power of EEG spectrum as well as neuronal necrosis. These data suggest that imidazenil is an effective anticonvulsant for medical countermeasure against soman-induced toxicity.

  11. Glycol ethers: a ubiquitous family of toxic chemicals: a plea for REACH regulation.

    PubMed

    Cicolella, André

    2006-09-01

    Glycol ethers (GE) are chemicals used since the 1930s as solvents in paints, inks, varnishes, and cleaning agents, mainly in water-based products, cosmetics, and drugs. World production approximates 1 million tons. Nineteen GE are produced or imported each year; over 1000 tons in European Union (EU) have been classified as high production volume chemicals (HPVCs). First animal data were published in 1971 and 1979 showing severe reprotoxicity for some GE. Two alerts were launched in the United States in 1982 and 1983, but the first partial GE regulation only occurred in 1993 in the EU. Although these chemicals may expose a very large population, basic toxicity data, more especially carcinogenicity, are still lacking (3/32 GE). However, experimental data were sufficient to lead developmental toxicity risk assessment since the early 1980s. Risk indices over 1000 have been calculated for consumers and workers exposed to reprotoxic GE in domestic and industrial activities. The first ban was decided in 1999 in France, but was only for drugs and cosmetics. Not surprisingly, since the late 1980s, human studies have found results similar to those in animal data: spontaneous abortions, malformations, testicular toxicity, and hematotoxicity. Despite this highly coherent set of data, and although substitution products are available, reprotoxic GE have been and still remain widely used in the world. The case of GE shows the failure of the present system based on a posteriori risk assessment. This pleads for the change of paradigm through the European REACH regulation based on the "No data, no market" principle. Ethics in REACH management should also be considered.

  12. Development of a QSAR for worst case estimates of acute toxicity of chemically reactive compounds.

    PubMed

    Freidig, A P; Dekkers, S; Verwei, M; Zvinavashe, E; Bessems, J G M; van de Sandt, J J M

    2007-05-15

    Future EU legislations enforce a fast hazard and risk assessment of thousands of existing chemicals. If conducted by means of present data requirements, this assessment will use a huge number of test animals and will be neither cost nor time effective. The purpose of the current research was to develop methods to increase the acceptability of in vitro data for classification and labelling regarding acute toxicity. For this purpose, a large existing database containing in vitro and in vivo data was analysed. For more than 300 compounds in the database, relations between in vitro cytotoxicity and rat or mouse intravenous and oral in vivo LD50 values were re-evaluated and the possibilities for definition of mechanism based chemical subclasses were investigated. A high in vitro-in vivo correlation was found for chemicals classified as irritants. This can be explained by a shared unspecific cytotoxicity of these compounds which will act as the predominant mode of action for both endpoints, irritation and acute toxicity. For this subclass, which covered almost 40% of all compounds in the database, the LD50 values after intravenous dosing could be predicted with high accuracy. A somewhat lower accuracy was found for the prediction of oral LD50 values based on in vitro cytotoxicity data. Based on this successful correlation, a classification and labelling scheme was developed, that includes a hazard based definition of the applicability domain (irritants) and a prediction of the labelling of compounds for their acute iv and oral toxicity. The scheme was tested by an external validation.

  13. Predicting Developmental Toxicity of ToxCast Phase I Chemicals Using Human Embryonic Stem Cells and Metabolomics

    EPA Science Inventory

    EPA’s ToxRefDB contains prenatal guideline study data from rats and rabbits for over 240 chemicals that overlap with the ToxCast in vitro high throughput screening project. A subset of these compounds were tested in Stemina Biomarker Discovery's developmental toxicity platform, a...

  14. Predicting Developmental Toxicity of ToxCast Phase I Chemicals Using Human Embryonic Stem Cells and Metabolomics

    EPA Science Inventory

    EPA’s ToxRefDB contains prenatal guideline study data from rats and rabbits for over 240 chemicals that overlap with the ToxCast in vitro high throughput screening project. A subset of these compounds were tested in Stemina Biomarker Discovery's developmental toxicity platform, a...

  15. Fate of chemical warfare agents and toxic industrial chemicals in landfills.

    PubMed

    Bartelt-Hunt, Shannon L; Barlaz, Morton A; Knappe, Detlef R U; Kjeldsen, Peter

    2006-07-01

    One component of preparedness for a chemical attack is planning for the disposal of contaminated debris. To assess the feasibility of contaminated debris disposal in municipal solid waste (MSW) landfills, the fate of selected chemical warfare agents (CWAs) and toxic industrial chemicals (TICs) in MSW landfills was predicted with a mathematical model. Five blister agents [sulfur mustard (HD), nitrogen mustard (HN-2), lewisite (L), ethyldichloroarsine (ED), and phosgene oxime (CX)], eight nerve agents [tabun (GA), sarin (GB), soman (GD), GE, GF, VX, VG, and VM], one riot-control agent [CS], and two TICs [furan and carbon disulfide] were studied. The effects of both infiltration (climate) and contaminant biodegradability on fate predictions were assessed. Model results showed that hydrolysis and gas-phase advection were the principal fate pathways for CWAs and TICs, respectively. Apart from CX and the TICs, none of the investigated compounds was predicted to persist in a landfill for more than 5 years. Climate had little impact on CWA/TIC fate, and biodegradability was only important for compounds with long hydrolysis half-lives. Monte Carlo simulations were performed to assess the influence of uncertainty in model input parameters on CWA/TIC fate predictions. Correlation analyses showed that uncertainty in hydrolysis rate constants was the primary contributor to variance of CWA fate predictions, while uncertainty in the Henry's Law constant and landfill gas-production rate accounted for most of the variance of TIC fate predictions. CWA hydrolysates were more persistent than the parent CWAs, but limited information is available on abiotic or biotic transformation rates for these chemicals.

  16. Biochemical strategies for the detection and detoxification of toxic chemicals in the environment

    PubMed Central

    Febbraio, Ferdinando

    2017-01-01

    Addressing the problems related to the widespread presence of an increasing number of chemicals released into the environment by human activities represents one of the most important challenges of this century. In the last few years, to replace the high cost, in terms of time and money, of conventional technologies, the scientific community has directed considerable research towards the development both of new detection systems for the measurement of the contamination levels of chemicals in people’s body fluids and tissue, as well as in the environment, and of new remediation strategies for the removal of such chemicals from the environment, as a means of the prevention of human diseases. New emerging biosensors for the analysis of environmental chemicals have been proposed, including VHH antibodies, that combine the antibody performance with the affinity for small molecules, genetically engineered microorganisms, aptamers and new highly stable enzymes. However, the advances in the field of chemicals monitoring are still far from producing a continuous real-time and on-line system for their detection. Better results have been obtained in the development of strategies which use organisms (microorganisms, plants and animals) or metabolic pathway-based approaches (single enzymes or more complex enzymatic solutions) for the fixation, degradation and detoxification of chemicals in the environment. Systems for enzymatic detoxification and degradation of toxic agents in wastewater from chemical and manufacturing industries, such as ligninolytic enzymes for the treatment of wastewater from the textile industry, have been proposed. Considering the high value of these research studies, in terms of the protection of human health and of the ecosystem, science must play a major role in guiding policy changes in this field. PMID:28289515

  17. Biochemical strategies for the detection and detoxification of toxic chemicals in the environment.

    PubMed

    Febbraio, Ferdinando

    2017-02-26

    Addressing the problems related to the widespread presence of an increasing number of chemicals released into the environment by human activities represents one of the most important challenges of this century. In the last few years, to replace the high cost, in terms of time and money, of conventional technologies, the scientific community has directed considerable research towards the development both of new detection systems for the measurement of the contamination levels of chemicals in people's body fluids and tissue, as well as in the environment, and of new remediation strategies for the removal of such chemicals from the environment, as a means of the prevention of human diseases. New emerging biosensors for the analysis of environmental chemicals have been proposed, including VHH antibodies, that combine the antibody performance with the affinity for small molecules, genetically engineered microorganisms, aptamers and new highly stable enzymes. However, the advances in the field of chemicals monitoring are still far from producing a continuous real-time and on-line system for their detection. Better results have been obtained in the development of strategies which use organisms (microorganisms, plants and animals) or metabolic pathway-based approaches (single enzymes or more complex enzymatic solutions) for the fixation, degradation and detoxification of chemicals in the environment. Systems for enzymatic detoxification and degradation of toxic agents in wastewater from chemical and manufacturing industries, such as ligninolytic enzymes for the treatment of wastewater from the textile industry, have been proposed. Considering the high value of these research studies, in terms of the protection of human health and of the ecosystem, science must play a major role in guiding policy changes in this field.

  18. Toxic organic chemicals in waste streams: anaerobic bioconversion to methane

    SciTech Connect

    Young, L.Y.

    1985-01-01

    Sixteen substituted aromatic compounds were evaluated for their anaerobic biodegradability and toxicity to methanogenesis with two standardized anaerobic bioassays. Each compound was the only added carbon source (20 to 200 mg/L) prepared in prereduced defined medium with a 10% (v/v) inoculum of municiple digester sludge. Four types of responses were observed: (1) all concentrations of benzoate, phenol, dibutyl phthalate and low concentrations (20 mg/L) of dimethyl and diethyl phthalate, 4-nitrophenol and 2,4-dinitrophenol were degraded to CH/sub 4/ and CO/sub 2/, attaining 50-100% of the theoretical gas yield; (2) high concentrations (200 mg/L) of diethyl and dimethyl phthalate, and low concentrations of 2-nitrophenol produced methane yields between 10 to 50% of the theoretical; (3) all concentrations of bis(2-ethylhexyl)phthalate, 2,4-dimethyl phenol, 4-chloro-m-cresol, ortho- and meta-cresol, 2-chlorophenol, intermediate concentrations (100 mg/L) of 2-nitrophenol and low concentrations of 4,6-dinitro-o-cresol yielded no more than 10% of the theoretical methane value; (4) high concentrations of 2-nitrophenol, 4-nitrophenol, 4,6-dinitro-o-cresol and 2,4-dinitrophenol exhibited a distinct suppression of methanogenesis from 10 to 90% below that of the background. Acclimation for most of the compounds took several days to weeks before degradation commenced. Thus, many of these compounds are metabolized in anoxic environments. Their fate may be significantly influenced by their concentration and residence time in such habitats. 35 refs., 33 figs., 12 tabs.

  19. Chemicals under the Toxic Substances Control Act (TSCA)

    EPA Pesticide Factsheets

    This web area will allow stakeholders to search and view centralized chemical info from various systems. This page will focus on TSCA chemical data such as health and safety studies, risk assessments and hazard characterizations.

  20. The aquatic toxicity and chemical forms of coke plant effluent cyanide -- Implications for discharge limits

    SciTech Connect

    Garibay, R.; Rupnow, M.; Godwin-Saad, E.; Hall, S.

    1995-12-31

    Cyanide is present in treated cokemaking process waters at concentrations as high as 8.0 mg/L. In assessing options for managing the discharge of a treated effluent, the development and implementation of discharge limits for cyanide became a critical issue. A study was initiated to evaluate possible alternatives to cyanide permit limits at the US Steel Gary Works Facility. The objectives of the study were to: (1) evaluation the forms of cyanide present in coke plant effluent; (2) determine whether these forms of cyanide are toxic to selected aquatic organisms; (3) compare the aquatic toxicity of various chemical forms of cyanide; (4) identify if the receiving water modifies cyanide bioavailability; and (5) confirm, with respect to water quality-based effluent limits, an appropriate analytical method for monitoring cyanide in a coke plant effluent. The results of aquatic toxicity tests and corresponding analytical data are presented. Toxicity tests were conducted with various pure chemical forms of cyanide as well as whole coke plant effluent (generated from a pilot-scale treatment system). Test species included the fathead minnow (Pimephales promelas), rainbow trout (Oncorhynchus mykiss), Ceriodaphnia dubia (C. dubia) and Daphnia magna (D. magna). Analytical measurements for cyanide included total, weak acid dissociable, diffusible cyanide and selected metal species of cyanide. The findings presented by the paper are relevant with respect to the application of cyanide water quality criteria for a coke plant effluent discharge, the translation of these water quality-based effluent limits to permit limits, and methods for compliance monitoring for cyanide.

  1. Metal Oxide Nanoparticles: The Importance of Size, Shape, Chemical Composition, and Valence State in Determining Toxicity

    NASA Astrophysics Data System (ADS)

    Dunnick, Katherine

    Nanoparticles, which are defined as a structure with at least one dimension between 1 and 100 nm, have the potential to be used in a variety of consumer products due to their improved functionality compared to similar particles of larger size. Their small size is associated with increased strength, improved catalytic properties, and increased reactivity; however, their size is also associated with increased toxicity in vitro and in vivo. Numerous toxicological studies have been conducted to determine the properties of nanomaterials that increase their toxicity in order to manufacture new nanomaterials with decreased toxicity. Data indicates that size, shape, chemical composition, and valence state of nanomaterials can dramatically alter their toxicity profile. Therefore, the purpose of this dissertation was to determine how altering the shape, size, and chemical composition of various metal oxide nanoparticles would affect their toxicity. Metal oxides are used in variety of consumer products, from spray-sun screens, to food coloring agents; thus, understanding the toxicity of metal oxides and determining which aspects affect their toxicity may provide safe alternatives nanomaterials for continued use in manufacturing. Tungstate nanoparticles toxicity was assessed in an in vitro model using RAW 264.7 cells. The size, shape, and chemical composition of these nanomaterials were altered and the effect on reactive oxygen species and general cytotoxicity was determined using a variety of techniques. Results demonstrate that shape was important in reactive oxygen species production as wires were able to induce significant reactive oxygen species compared to spheres. Shape, size, and chemical composition did not have much effect on the overall toxicity of these nanoparticles in RAW 264.7 cells over a 72 hour time course, implicating that the base material of the nanoparticles was not toxic in these cells. To further assess how chemical composition can affect toxicity

  2. Toxic, bioaccumulative and persistent chemicals in central and eastern Europe--state-of-the-art report.

    PubMed

    Holoubek, I

    2000-07-01

    Organic substances that are persistent, bioaccumulative and have toxic characteristics likely to cause adverse effects on human health or have environmental effects are called PBTs (Persistent, Bioaccumulative, Toxic substances). The report "Persistent, Bioaccumulative and Toxic Chemicals in Central and Eastern European Countries--State-of-the-art Report" was prepared by a group of scientists from the Czech Republic, Slovakia, Poland and Estonia and was published on the Internet (http:¿recetox.chemi.muni.cz/).

  3. Integration of chemical-specific exposure and pharmacokinetic information with the chemical-agnostic AOP framework to support high throughput risk assessment

    EPA Science Inventory

    Application of the Adverse Outcome Pathway (AOP) framework and high throughput toxicity testing in chemical-specific risk assessment requires reconciliation of chemical concentrations sufficient to trigger a molecular initiating event measured in vitro and at the relevant target ...

  4. Integration of chemical-specific exposure and pharmacokinetic information with the chemical-agnostic AOP framework to support high throughput risk assessment

    EPA Science Inventory

    Application of the Adverse Outcome Pathway (AOP) framework and high throughput toxicity testing in chemical-specific risk assessment requires reconciliation of chemical concentrations sufficient to trigger a molecular initiating event measured in vitro and at the relevant target ...

  5. CHEMICAL STRUCTURE INDEXING OF TOXICITY DATA ON THE INTERNET: MOVING TOWARDS A FLAT WORLD

    EPA Science Inventory

    Standardized chemical structure annotation of public toxicity databases and information resources is playing an increasingly important role in the 'flattening' and integration of diverse sets of biological activity data on the Internet. This review discusses public initiatives th...

  6. LINKING EFFECTS OF PERSISTENT BIOACCUMULATIVE TOXICANTS TO CHEMICAL EXPOSURES IN AQUATIC ECOSYSTEMS

    EPA Science Inventory

    The critical step in characterization of ecological risks associated with exposures of fish and wildlife to persistent bioaccumulative toxicants (PBTs) is linking chemical residue based toxicological data to concentrations of PBTs in sediments, water, and biota. This is necessary...

  7. Impact of toxic chemicals on local wastewater treatment plant and the environment

    NASA Astrophysics Data System (ADS)

    Bennett, Gary F.

    1989-05-01

    Because toxic chemicals being discharged to sewers were simultaneously interfering with wastewater treatment processes of municipal, biological treatment plants and were passing through these plants to negatively impact the bodies of water to which these plants were discharging, the U.S. Environmental Protection Agency issued regulations governing industrial discharges to municipal sewers. These “Pretreatment Regulations” limit industrial discharges to municipal sewers of heavy metals, oil and grease, acids and bases, and toxic organic chemicals. This paper discusses the evolution of these regulations, the basis for them, the types of regulations (categorical and local), and the rationale for their promulgation based on the impacts of toxics chemicals on the treatment plant and receiving system. Finally, the expected results of these regulations in reducing industrial discharges of toxic chemicals is discussed.

  8. 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...

  9. CHEMICAL STRUCTURE INDEXING OF TOXICITY DATA ON THE INTERNET: MOVING TOWARDS A FLAT WORLD

    EPA Science Inventory

    Standardized chemical structure annotation of public toxicity databases and information resources is playing an increasingly important role in the 'flattening' and integration of diverse sets of biological activity data on the Internet. This review discusses public initiatives th...

  10. 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...

  11. Fact Sheet: Final Air Toxics Standards for Area Sources in the Chemical Manufacturing Industry

    EPA Pesticide Factsheets

    Fact sheet on the national air toxics standards issued October 16, 2009 by the Environmental Protection Agency (EPA) for smaller-emitting sources, known as area sources, in the chemical manufacturing industry.

  12. The comparative toxicity to soil invertebrates of natural chemicals and their synthetic analogues.

    PubMed

    Whitaker, J; Chaplow, J S; Potter, E; Scott, W A; Hopkin, S; Harman, M; Sims, I; Sorokin, N

    2009-07-01

    The introduction of Registration, Evaluation and Authorisation of Chemicals (REACH), requires companies to register and risk assess all substances produced or imported in volumes of >1 tonne per year. Extrapolation methods which use existing data for estimating the effects of chemicals are attractive to industry, and comparative data are therefore increasingly in demand. Data on natural toxic chemicals could be used for extrapolation methods such as read-across. To test this hypothesis, the toxicity of natural chemicals and their synthetic analogues were compared using standardised toxicity tests. Two chemical pairs: the napthoquinones, juglone (natural) and 1,4-naphthoquinone (synthetic); and anthraquinones, emodin (natural) and quinizarin (synthetic) were chosen, and their comparative effects on the survival and reproduction of collembolans, earthworms, enchytraeids and predatory mites were assessed. Differences in sensitivity between the species were observed with the predatory mite (Hypoaspis aculeifer) showing the least sensitivity. Within the chemical pairs, toxicity to lethal and sub-lethal endpoints was very similar for the four invertebrate species. The exception was earthworm reproduction, which showed differential sensitivity to the chemicals in both naphthoquinone and anthraquinone pairs. Differences in toxicity identified in the present study may be related to degree of exposure and/or subtle differences in the mode of toxic action for the chemicals and species tested. It may be possible to predict differences by identifying functional groups which infer increased or decreased toxicity in one or other chemical. The development of such techniques would enable the use of read-across from natural to synthetic chemicals for a wider group of compounds.

  13. VAPOR SAMPLING DEVICE FOR INTERFACE WITH MICROTOX ASSAY FOR SCREENING TOXIC INDUSTRIAL CHEMICALS

    EPA Science Inventory

    A time-integrated sampling system interfaced with a toxicity-based assay is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethyl sulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

  14. 76 FR 38170 - Toxic Substances Control Act Chemical Testing; Receipt of Test Data

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-29

    ...: Kathy Calvo, Chemical Control Division (7405M), Office of Pollution Prevention and Toxics, Environmental... 0290.1, pg. 15; and 1782 (thermal analysis). 0290.2. n-Octanol/Water Partition 0290, 0290.1, pg. 17..., Office of Pollution Prevention and Toxics. BILLING CODE 6560-50-P...

  15. QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP (QSAR) MODELS TO PREDICT CHEMICAL TOXICITY FOR VARIOUS HEALTH ENDPOINTS

    EPA Science Inventory

    Although ranking schemes based on exposure and toxicity have been developed to aid in the prioritization of research funds for identifying chemicals of regulatory concern, there are significant gaps in the availability of experimental toxicity data for most health endpoints. Pred...

  16. QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP (QSAR) MODELS TO PREDICT CHEMICAL TOXICITY FOR VARIOUS HEALTH ENDPOINTS

    EPA Science Inventory

    Although ranking schemes based on exposure and toxicity have been developed to aid in the prioritization of research funds for identifying chemicals of regulatory concern, there are significant gaps in the availability of experimental toxicity data for most health endpoints. Pred...

  17. VAPOR SAMPLING DEVICE FOR INTERFACE WITH MICROTOX ASSAY FOR SCREENING TOXIC INDUSTRIAL CHEMICALS

    EPA Science Inventory

    A time-integrated sampling system interfaced with a toxicity-based assay is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethyl sulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

  18. Exposure to toxic chemicals in the diet: is the Brazilian population at risk?

    PubMed

    Caldas, Eloisa Dutra; Jardim, Andreia Nunes Oliveira

    2012-01-01

    In Brazil, in the last 20 years, dietary risk assessments have been conducted on pesticides, mycotoxins, food additives, heavy metals (mainly mercury), environmental contaminants (mainly DDT) and acrylamide, a compound formed during food processing. The objectives of this paper were to review these studies, discuss their limitations and uncertainties and identify the most critical chemicals that may pose a health risk to Brazilian consumers. The studies have shown that the cumulative intake of organophosphorus and carbamate pesticides by high consumers of fruits and vegetables may represent a health concern (up to 169% of the ARfD), although the benefits of consuming large portions of those foods most probably overcome the risks. High consumers of maize products may also be at risk due to the presence of fumonisin (355% of the PMTDI), a mycotoxin present at high levels in Brazilian maize. The studies conducted in the Brazilian Amazon have shown that riparian fish consumers are exposed to unsafe levels of mercury. However, this is a more complex issue, as mercury levels in the region are naturally high and the health benefits of a fish-based diet are well known. Studies conducted both in Brazil and internationally on acrylamide have shown that the exposure to this genotoxic compound, mainly from the consumption of French fries and potato chips, is of health concern. Reducing the population dietary exposure to toxic chemicals is a challenge for government authorities and food producers in all countries. Management strategies aimed at decreasing exposure to the critical chemicals identified in this review involve limiting the use or eliminating highly toxic pesticides, implementing good agricultural practices to decrease maize contamination by fumonisins, educating local fish-eating communities toward a fish diet less contaminated by mercury, and changing dietary habits concerning the consumption of fried potatoes, the main processed food containing acrylamide.

  19. Toxicity of organic chemical pollution in groundwater downgradient of a landfill (Grindsted, Denmark)

    SciTech Connect

    Baun, A.; Jensen, S.D.; Bjerg, P.L.; Christensen, T.H.; Nyholm, N.

    2000-05-01

    The aim of the present study was to describe the occurrence and distribution of toxicity related to organic chemical contaminants in the leachate plume downgradient of the Grindsted Landfill (Denmark). A total of 27 groundwater samples were preconcentrated by solid-phase extraction (SPE) using XAD-2 as the resin material. This treatment effectively eliminated sample matrix toxicity caused by inorganic salts and natural organic compounds and produced an aqueous concentrate of the nonvolatile chemical contaminants. The SPE extracts were tested in a battery of standardized short-term aquatic toxicity tests with luminescent bacteria (Vibrio fischeri), algae (Selenastrum capricornutum), and crustaceans (Daphnia magna). Additional genotoxicity tests were made using the umuC test (Salmonella typhimurium). Biotests with algae and luminescent bacteria were the most sensitive tests. On the basis of results with these two bioassays, it was concluded that SPE extracts of groundwater collected close to the landfill were toxic. The toxicity decreased with the distance from the landfill. At distances greater than 80 m from the border of the landfill, the groundwater toxicity was not significantly different from the background toxicity. SPE extracts were not toxic to Daphnia, and no genotoxicity was observed in the umuC test. The overall findings indicate that a battery of biotests applied on preconcentrated groundwater samples can be a useful tool for toxicity characterization and hazard ranking of groundwater polluted with complex chemical mixtures, such as landfill leachates.

  20. Colorimetric sensor array for determination and identification of toxic industrial chemicals.

    PubMed

    Feng, Liang; Musto, Christopher J; Kemling, Jonathan W; Lim, Sung H; Zhong, Wenxuan; Suslick, Kenneth S

    2010-11-15

    A low-cost yet highly sensitive colorimetric sensor array for the detection and identification of toxic industrial chemicals (TICs) has been developed. The sensor consists of a disposable array of cross-responsive nanoporous pigments whose colors are changed by diverse chemical interactions with analytes. Clear differentiation among 20 different TICs has been easily achieved at both their IDLH (immediately dangerous to life or health) concentration within 2 min of exposure and PEL (permissible exposure limit) concentration within 5 min of exposure with no errors or misclassifications. Detection limits are generally well below the PEL (in most cases below 5% of PEL) and are typically in the low ppb range. The colorimetric sensor array is not responsive to changes in humidity or temperature over a substantial range. The printed arrays show excellent batch to batch reproducibility and long shelf life (greater than 3 months).

  1. [Characteristic of toxic risks of air pollution by chemical admixtures aboard the piloted orbital stations].

    PubMed

    Mukhamedieva, L N; Bogomolov, V V

    2009-01-01

    Trends in the chemical composition of air revealed by the sanitary-chemical and toxicological investigations in multifactorial ground-based tests and long-term space flights aboard the Salyut- 6, 7, Mir and the International space station have been used to deduce the chemical characteristic and to substantiate methods to and criteria for evaluation of toxic risks to space crews from air chemical pollution. Of particular concern were the toxic risks and crew protection during the first ingress to modules on the stage of station assembly in orbit, in the course of long-term missions, and in the event of acute exposure in off-nominal and emergency conditions.

  2. Toxicity to freshwater organisms from oils and oil spill chemical treatments in laboratory microcosms.

    PubMed

    Bhattacharyya, S; Klerks, P L; Nyman, J A

    2003-01-01

    Toxicity and temporal changes in toxicity of freshwater-marsh-microcosms containing South Louisiana Crude (SLC) or diesel fuel and treated with a cleaner or dispersant, were investigated using Chironomus tentans, Daphnia pulex, and Oryzias latipes. Bioassays used microcosm water (for D. pulex and O. latipes) or soil slurry (for C. tentans) taken 1,7, 31, and 186 days after treatment. SLC was less toxic than diesel, chemical additives enhanced oil toxicity, the dispersant was more toxic than the cleaner, and toxicities were greatly reduced by day 186. Toxicities were higher in the bioassay with the benthic species than in those with the two water-column species. A separate experiment showed that C. tentans' sensitivity was intermediate to that of Tubifex tubifex and Hyallela azteca. Freshwater organisms, especially benthic invertebrates, thus appear seriously effected by oil under the worst-case-scenario of our microcosms. Moreover, the cleaner and dispersant tested were poor response options under those conditions.

  3. Predicting the future: opportunities and challenges for the chemical industry to apply 21st-century toxicity testing.

    PubMed

    Settivari, Raja S; Ball, Nicholas; Murphy, Lynea; Rasoulpour, Reza; Boverhof, Darrell R; Carney, Edward W

    2015-03-01

    Interest in applying 21st-century toxicity testing tools for safety assessment of industrial chemicals is growing. Whereas conventional toxicology uses mainly animal-based, descriptive methods, a paradigm shift is emerging in which computational approaches, systems biology, high-throughput in vitro toxicity assays, and high-throughput exposure assessments are beginning to be applied to mechanism-based risk assessments in a time- and resource-efficient fashion. Here we describe recent advances in predictive safety assessment, with a focus on their strategic application to meet the changing demands of the chemical industry and its stakeholders. The opportunities to apply these new approaches is extensive and include screening of new chemicals, informing the design of safer and more sustainable chemical alternatives, filling information gaps on data-poor chemicals already in commerce, strengthening read-across methodology for categories of chemicals sharing similar modes of action, and optimizing the design of reduced-risk product formulations. Finally, we discuss how these predictive approaches dovetail with in vivo integrated testing strategies within repeated-dose regulatory toxicity studies, which are in line with 3Rs principles to refine, reduce, and replace animal testing. Strategic application of these tools is the foundation for informed and efficient safety assessment testing strategies that can be applied at all stages of the product-development process.

  4. Predicting the Future: Opportunities and Challenges for the Chemical Industry to Apply 21st-Century Toxicity Testing

    PubMed Central

    Settivari, Raja S; Ball, Nicholas; Murphy, Lynea; Rasoulpour, Reza; Boverhof, Darrell R; Carney, Edward W

    2015-01-01

    Interest in applying 21st-century toxicity testing tools for safety assessment of industrial chemicals is growing. Whereas conventional toxicology uses mainly animal-based, descriptive methods, a paradigm shift is emerging in which computational approaches, systems biology, high-throughput in vitro toxicity assays, and high-throughput exposure assessments are beginning to be applied to mechanism-based risk assessments in a time- and resource-efficient fashion. Here we describe recent advances in predictive safety assessment, with a focus on their strategic application to meet the changing demands of the chemical industry and its stakeholders. The opportunities to apply these new approaches is extensive and include screening of new chemicals, informing the design of safer and more sustainable chemical alternatives, filling information gaps on data-poor chemicals already in commerce, strengthening read-across methodology for categories of chemicals sharing similar modes of action, and optimizing the design of reduced-risk product formulations. Finally, we discuss how these predictive approaches dovetail with in vivo integrated testing strategies within repeated-dose regulatory toxicity studies, which are in line with 3Rs principles to refine, reduce, and replace animal testing. Strategic application of these tools is the foundation for informed and efficient safety assessment testing strategies that can be applied at all stages of the product-development process. PMID:25836969

  5. Effects-driven chemical fractionation of heavy fuel oil to isolate compounds toxic to trout embryos.

    PubMed

    Bornstein, Jason M; Adams, Julie; Hollebone, Bruce; King, Thomas; Hodson, Peter V; Brown, R Stephen

    2014-04-01

    Heavy fuel oil (HFO) spills account for approximately 60% of ship-source oil spills and are up to 50 times more toxic than medium and light crude oils. Heavy fuel oils contain elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and alkyl-PAHs, known to be toxic to fish; however, little direct characterization of HFO toxicity has been reported. An effects-driven chemical fractionation was conducted on HFO 7102 to separate compounds with similar chemical and physical properties, including toxicity, to isolate the groups of compounds most toxic to trout embryos. After each separation, toxicity tests directed the next phase of fractionation, and gas chromatography-mass spectrometry analysis correlated composition with toxicity, with a focus on PAHs. Low-temperature vacuum distillation permitted the separation of HFO into 3 fractions based on boiling point ranges. The most toxic of these fractions underwent wax precipitation to remove long-chain n-alkanes. The remaining PAH-rich extract was further separated using open column chromatography, which provided distinct fractions that were grouped according to increasing aromatic ring count. The most toxic of these fractions was richest in PAHs and alkyl-PAHs. The results of the present study were consistent with previous crude oil studies that identified PAH-rich fractions as the most toxic.

  6. Handbook of acute toxicity of chemicals to fish and aquatic invertebrates : summaries of toxicity tests conducted at Columbia National Fisheries Research Laboratory, 1965-78

    USGS Publications Warehouse

    Johnson, W. Waynon; Finley, Mack T.

    1980-01-01

    Acute toxicity is a major subject of research at Columbia National Fisheries Research Laboratory for evaluating the impact of toxic chemicals on fishery resources. The Laboratory has played a leading role in developing research technology for toxicity testing and data interpretation. In 1965-78, more than 400 chemicals were tested against a variety of invertebrates and fish species representative of both cold- and warm-water climates.The use of acute toxicity tests for assessing the potential hazard of chemical contaminants to aquatic organisms is well documented (Boyd 1957; Henderson et al. 1960; Sanders and Cope 1966; Macek and McAllister 1970). Static acute toxicity tests provide rapid and (within limits) reproducible concentration-response curves for estimating toxic effects of chemicals on aquatic organisms. These tests provide a database for determining relative toxicity of a large number of chemicals to a variety of species and for estimating acute effects of chemical spills on natural aquatic systems; they also assist in determining priority and design of additional toxicity studies.Acute toxicity tests usually provide estimates of the exposure concentration causing 50% mortality (LC50) to test organisms during a specified period of time. For certain invertebrates, the effective concentration is based on immobilization, or some other identifiable endpoint, rather than on lethality. The application of the LC50 has gained acceptance among toxicologists and is generally the most highly rated test for assessing potential adverse effects of chemical contaminants to aquatic life (Brungs and Mount 1978; American Institute for Biological Sciences 1978a).The literature contains numerous papers dealing with the acute toxicity of chemicals to freshwater organisms. However, there is a tremendous need for a concise compendium of toxicity data covering a large variety of chemicals and test species. This Handbook is a compilation of a large volume of acute toxicity data

  7. Meta-analysis of aquatic chronic chemical toxicity data

    EPA Science Inventory

    Chronic toxicity data from the open literature and from tests submitted for pesticide registration were extracted and assembled into a database, AquaChronTox, with a flexible search interface. Data were captured at a treatment and, when available, replicate level to support conc...

  8. DIFFERENTIATING MECHANISMS OF REACTIVE CHEMICAL TOXICITY IN ISOLATED TROUT HEPATOCYTES

    EPA Science Inventory

    The toxicity of four quinones, 2,3-dimethoxy-1,4-naphthoquinone (DMONQ), 2-methyl 1,4-naphthoquinone (MNQ ),1,4-naphthoquinone (NQ), and 1,4-benzoquinone (BQ), which redox cycle or arlyate in mammalian cells, was determined in isolated trout (Oncorhynchus mykiss) hepatocytes. Mor...

  9. DIFFERENTIATING MECHANISMS OF REACTIVE CHEMICAL TOXICITY IN ISOLATED TROUT HEPATOCYTES

    EPA Science Inventory

    The toxicity of four quinones, 2,3-dimethoxy-1,4-naphthoquinone (DMONQ), 2-methyl 1,4-naphthoquinone (MNQ ),1,4-naphthoquinone (NQ), and 1,4-benzoquinone (BQ), which redox cycle or arlyate in mammalian cells, was determined in isolated trout (Oncorhynchus mykiss) hepatocytes. Mor...

  10. Meta-analysis of aquatic chronic chemical toxicity data

    EPA Science Inventory

    Chronic toxicity data from the open literature and from tests submitted for pesticide registration were extracted and assembled into a database, AquaChronTox, with a flexible search interface. Data were captured at a treatment and, when available, replicate level to support conc...

  11. Acute toxicity of fire control chemicals to Daphnia magna (Straus) and Selenastrum capricornutum (Printz).

    PubMed

    McDonald, S F; Hamilton, S J; Buhl, K J; Heisinger, J F

    1996-02-01

    Acute toxicity tests were conducted exposing Daphnia magna Straus (daphnid) in soft and hard reconstituted waters (hardness 42 and 162 mg/liter as CaCO3, respectively), and Selenastrum capricornutum Printz (algae) in ASTM algal assay medium (hardness 15 mg/liter as CaCO3) to fire retardants Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F, and foam suppressants Phos-Check WD-881 and Silv-Ex. The chemicals were slightly toxic to practically harmless to daphnids and moderately toxic to algae. Water quality did not consistently alter the toxicity of the test chemicals to daphnids. The most toxic chemical to daphnids was Silv-Ex (48-hr EC50 7 mg/liter in soft and hard waters), whereas the least toxic chemical to daphnids was Fire-Trol LCG-R (48-hr EC50 848 mg/liter in soft water, 813 mg/liter in hard water). The most toxic chemical to algae was Fire-Trol LCG-R (96-hr IC50 10 mg/liter), and the least toxic chemical was Phos-Chek D75-F (96-hr IC50 79 mg/liter). Un-ionized ammonia concentrations near the EC50 or IC50 value in tests with the Fire-Trol compounds were frequently equal to or above reported LC50 un-ionized ammonia concentrations. Un-ionized ammonia concentrations in tests with Phos-Chek D75-F were low, thus other toxic components present in the compounds probably contributed to the toxicity. When compared to the daphnids tested in ASTM soft water, the Fire-Trol compounds were most toxic to algae, whereas Phos-Chek D75-F and the foam suppressants were most toxic to daphnids. The results of these tests are comparable to those obtained from research conducted in other laboratories with the same species and similar chemicals. Accidental entry of fire-fighting chemicals into aquatic environments could adversely affect algae and aquatic invertebrates, thus disrupting ecosystem function.

  12. Acute toxicity of fire control chemicals to Daphnia magna(Straus) and Selenastrum capricornutum(Printz)

    USGS Publications Warehouse

    McDonald, Susan F.; Hamilton, Steven J.; Buhl, Kevin J.; Heisinger, James F.

    1996-01-01

    Acute toxicity tests were conducted exposingDaphnia magnaStraus (daphnid) in soft and hard reconstituted waters (hardness 42 and 162 mg/liter as CaCO3, respectively), andSelenastrum capricornutumPrintz (algae) in ASTM algal assay medium (hardness 15 mg/liter as CaCO3) to fire retardants Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F, and foam suppressants Phos-Chek WD-881 and Silv-Ex. The chemicals were slightly toxic to practically harmless to daphnids and moderately toxic to algae. Water quality did not consistently alter the toxicity of the test chemicals to daphnids. The most toxic chemical to daphnids was Silv-Ex (48-hr EC507 mg/liter in soft and hard waters), whereas the least toxic chemical to daphnids was Fire-Trol LCG-R (48-hr EC50848 mg/liter in soft water, 813 mg/liter in hard water). The most toxic chemical to algae was Fire-Trol LCG-R (96-hr IC5010 mg/liter), and the least toxic chemical was Phos-Chek D75-F (96-hr IC5079 mg/liter). Un-ionized ammonia concentrations near the EC50or IC50value in tests with the Fire-Trol compounds were frequently equal to or above reported LC50un-ionized ammonia concentrations. Un-ionized ammonia concentrations in tests with Phos-Chek D75-F were low, thus other toxic components present in the compounds probably contributed to the toxicity. When compared to the daphnids tested in ASTM soft water, the Fire-Trol compounds were most toxic to algae, whereas Phos-Chek D75-F and the foam suppressants were most toxic to daphnids. The results of these tests are comparable to those obtained from research conducted in other laboratories with the same species and similar chemicals. Accidental entry of fire-fighting chemicals into aquatic environments could adversely affect algae and aquatic invertebrates, thus disrupting ecosystem function.

  13. Chemical modification : a non-toxic approach to wood preservation

    Treesearch

    Roger M. Rowell

    2006-01-01

    Wood can be chemically modified to reduce the moisture content of the cell wall and increases decay resistance. As the level of bonded chemical increases, the cell wall equilibrium moisture content decreases and the resistance to attack by white-and brown-rot fungi increases. There is a direct relationship between the decrease in cell wall moisture Content and...

  14. Preventing and Managing Toxicities of High-Dose Methotrexate.

    PubMed

    Howard, Scott C; McCormick, John; Pui, Ching-Hon; Buddington, Randall K; Harvey, R Donald

    2016-12-01

    : High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m(2), is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI) in 2%-12% of patients. Nephrotoxicity results from crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. AKI and other toxicities of high-dose methotrexate can lead to significant morbidity, treatment delays, and diminished renal function. Risk factors for methotrexate-associated toxicity include a history of renal dysfunction, volume depletion, acidic urine, and drug interactions. Renal toxicity leads to impaired methotrexate clearance and prolonged exposure to toxic concentrations, which further worsen renal function and exacerbate nonrenal adverse events, including myelosuppression, mucositis, dermatologic toxicity, and hepatotoxicity. Serum creatinine, urine output, and serum methotrexate concentration are monitored to assess renal clearance, with concurrent hydration, urinary alkalinization, and leucovorin rescue to prevent and mitigate AKI and subsequent toxicity. When delayed methotrexate excretion or AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase are usually sufficient to allow renal recovery without the need for dialysis. Prompt recognition and effective treatment of AKI and associated toxicities mitigate further toxicity, facilitate renal recovery, and permit patients to receive other chemotherapy or resume HDMTX therapy when additional courses are indicated.

  15. Toxicity of the organophosphate chemical warfare agents GA, GB, and VX: Implications for public protection

    SciTech Connect

    Munro, N.B.; Ambrose, K.R.; Watson, A.P. )

    1994-01-01

    The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is not evidence that it causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxicity, the nerve agent exposure is the extraordinarily high acute toxicity of these substances. Futhermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent release, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. 187 refs., 3 figs., 7 tabs.

  16. Toxicity of the Organophosphate Chemical Warfare Agents GA, GB, and VX: Implications for Public Protection.

    PubMed Central

    Munro, N

    1994-01-01

    The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is no evidence that it causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxcity, the nerve agents are not likely to be carcinogens. The overreaching concern with regard to nerve agent exposure is the extraordinarily high acute toxicity of these substances. Furthermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent releaase, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. Images Figure 2. PMID:9719666

  17. Toxicity of the organophosphate chemical warfare agents GA, GB, and VX: implications for public protection.

    PubMed

    Munro, N

    1994-01-01

    The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is no evidence that it causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxicity, the nerve agents are not likely to be carcinogens. The overreaching concern with regard to nerve agent exposure is the extraordinarily high acute toxicity of these substances. Furthermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent release, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs.

  18. Children's vulnerability to toxic chemicals: a challenge and opportunity to strengthen health and environmental policy.

    PubMed

    Landrigan, Philip J; Goldman, Lynn R

    2011-05-01

    A key policy breakthrough occurred nearly twenty years ago with the discovery that children are far more sensitive than adults to toxic chemicals in the environment. This finding led to the recognition that chemical exposures early in life are significant and preventable causes of disease in children and adults. We review this knowledge and recommend a new policy to regulate industrial and consumer chemicals that will protect the health of children and all Americans, prevent disease, and reduce health care costs. The linchpins of a new US chemical policy will be: first, a legally mandated requirement to test the toxicity of chemicals already in commerce, prioritizing chemicals in the widest use, and incorporating new assessment technologies; second, a tiered approach to premarket evaluation of new chemicals; and third, epidemiologic monitoring and focused health studies of exposed populations.

  19. Membrane alterations following toxic chemical insult. Research progress report No. 3 (Final), 15 July 1984-31 January 1988

    SciTech Connect

    Liss, A.

    1988-03-10

    A procaryotic cell system was developed that can be used to determine the toxic action of chemicals acting at the level of the eucaryotic or procaryotic cytoplasmic membrane. Cell wall-less microbes known as mycoplasmas were used. In this current study, two perfluorinated fatty acids (CB and C10) were found to inhibit the growth of the test mycoplasmas. Two apparent activities, cytotoxicity and cytolysis, were observed. At high concentrations (>10 mM), a detergent-like action was noted. At low concentrations (<10 mM), cell death was observed without detectable cell lysis. Altering the cell membrane (the presumed target of the toxic compounds) resulted in altered levels to toxicity. Similar results were obtained when human or murine B-cells were used as the target organism. The toxic action of the perfluorinated fatty acids apparently involves some interaction with the membrane of the cells being treated.

  20. A simple, rapid, inexpensive assay for toxic chemicals using a bacterial indicator

    SciTech Connect

    Botsford, J.L.; Hillaker, T.; Robertson, B.; Gonzales, M.; Benavidez, M.; Jones, B.; Baker, R.; Steen, W.; Pacheco, F.; Homer, V.; Lucero, O.; Matthews, M.; Koehler, V.

    1996-12-31

    A simple test for toxic chemicals has been developed. Rhizobium meliloti is combined with the toxic chemical. A tetrazolium dye, MTT (3-[4,5-Dimethylthiazol-2-yl]2,5-diphenyl-tetrazolium bromide) is added. The bacterium reduces this dye, causing the optical absorbance to increase dramatically. The increase can be determined with a simple spectrophotometer. Toxic chemicals and minerals inhibit the reduction of the dye. Presumably the dye serves as a terminal electron acceptor for electron transport. Toxic substances presumably damage the electron transport system. The results compare favorably with published results of tests using the Microtox{trademark} assay and with the Polytox{trademark} assay. This assay is simpler and requires no specialized equipment. It should be possible to use this assay in a third world situation.

  1. Estimating the toxicities of organic chemicals to bioluminescent bacteria and activated sludge.

    PubMed

    Ren, Shijin; Frymier, Paul D

    2002-10-01

    Toxicity assays based on bioluminescent bacteria have several advantages including a quick response and an easily measured signal. The Shk1 assay is a procedure for wastewater toxicity testing based on the bioluminescent bacterium Shk1. Using the Shk1 assay, the toxicity of 98 organic chemicals were measured and EC50 values were obtained. Quantitative structure-activity relationship (QSAR) models based on the logarithm of the octanol-water partition coefficient (log(Kow)) were developed for individual groups of organic chemicals with different functional groups. The correlation coefficients for different groups of organic compounds varied between 0.69 and 0.99. An overall QSAR model without discriminating the functional groups, which can be used for a quick estimate of the toxicities of organic chemicals, was also developed and model predictions were compared to experimental data. The model accuracy was found to be one order of magnitude from the observed values.

  2. The combined toxic effects of nonpolar narcotic chemicals to Pseudokirchneriella subcapitata.

    PubMed

    Hsieh, Shih-Hung; Tsai, Kuo-Pei; Chen, Chung-Yuan

    2006-06-01

    This paper presents the toxicity data of 10 nonpolar narcotic chemicals on Pseudokirchneriella subcapitata (green algae) assessed by a new algal toxicity testing technique conducted under air-tight environment. Based on DO production, median effective concentration (EC50) varies from 1.73 mg/L (1-octanol) to 8,040 mg/L (2-propanol). The endpoint of algal growth rate reveals similar sensitivity as that from DO production. Compared to literature data, Pseudokirchneriella subcapitata and Nitrosomonas are apparently more sensitive to nonpolar narcotics than other organisms such as minnow, daphnia, and Tetrahymena pyriformis. Furthermore, good correlations between toxic effects observed from Pseudokirchneriella subcapitata and other aquatic organisms were found. Hence, algal toxicity test can be considered as a surrogate test for estimating the toxicity of nonpolar chemicals to fathead minnow, Microtox, activated sludge, Daphina magna, and Tetrahymena pyriformis. The combined effects of 13 binary mixtures of nonpolar chemicals were investigated using both additive-index method and isobologram analysis. Overall speaking, the joint actions between these chemicals are strictly additive. Model analyses indicate that these compounds act on identical reaction sites or receptors, which verify that these chemicals are of the same toxicity mechanism (narcosis).

  3. Evidence of Coal-Fly-Ash Toxic Chemical Geoengineering in the Troposphere: Consequences for Public Health

    PubMed Central

    Herndon, J. Marvin

    2015-01-01

    The widespread, intentional and increasingly frequent chemical emplacement in the troposphere has gone unidentified and unremarked in the scientific literature for years. The author presents evidence that toxic coal combustion fly ash is the most likely aerosolized particulate sprayed by tanker-jets for geoengineering, weather-modification and climate-modification purposes and describes some of the multifold consequences on public health. Two methods are employed: (1) Comparison of 8 elements analyzed in rainwater, leached from aerosolized particulates, with corresponding elements leached into water from coal fly ash in published laboratory experiments, and (2) Comparison of 14 elements analyzed in dust collected outdoors on a high-efficiency particulate air (HEPA) filter with corresponding elements analyzed in un-leached coal fly ash material. The results show: (1) the assemblage of elements in rainwater and in the corresponding experimental leachate are essentially identical. At a 99% confidence interval, they have identical means (T-test) and identical variances (F-test); and (2) the assemblage of elements in the HEPA dust and in the corresponding average un-leached coal fly ash are likewise essentially identical. The consequences on public health are profound, including exposure to a variety of toxic heavy metals, radioactive elements, and neurologically-implicated chemically mobile aluminum released by body moisture in situ after inhalation or through transdermal induction. PMID:26270671

  4. Evidence of Coal-Fly-Ash Toxic Chemical Geoengineering in the Troposphere: Consequences for Public Health.

    PubMed

    Herndon, J Marvin

    2015-08-11

    The widespread, intentional and increasingly frequent chemical emplacement in the troposphere has gone unidentified and unremarked in the scientific literature for years. The author presents evidence that toxic coal combustion fly ash is the most likely aerosolized particulate sprayed by tanker-jets for geoengineering, weather-modification and climate-modification purposes and describes some of the multifold consequences on public health. Two methods are employed: (1) Comparison of 8 elements analyzed in rainwater, leached from aerosolized particulates, with corresponding elements leached into water from coal fly ash in published laboratory experiments, and (2) Comparison of 14 elements analyzed in dust collected outdoors on a high-efficiency particulate air (HEPA) filter with corresponding elements analyzed in un-leached coal fly ash material. The results show: (1) the assemblage of elements in rainwater and in the corresponding experimental leachate are essentially identical. At a 99% confidence interval, they have identical means (T-test) and identical variances (F-test); and (2) the assemblage of elements in the HEPA dust and in the corresponding average un-leached coal fly ash are likewise essentially identical. The consequences on public health are profound, including exposure to a variety of toxic heavy metals, radioactive elements, and neurologically-implicated chemically mobile aluminum released by body moisture in situ after inhalation or through transdermal induction.

  5. Toxic essential oils. Part II: chemical, toxicological, pharmacological and microbiological profiles of Artemisia annua L. volatiles.

    PubMed

    Radulović, Niko S; Randjelović, Pavle J; Stojanović, Nikola M; Blagojević, Polina D; Stojanović-Radić, Zorica Z; Ilić, Ivan R; Djordjević, Vidosava B

    2013-08-01

    Botanical drugs based on Artemisia annua L. (Asteraceae) are important in the treatment of malaria. Alongside with artemisinin, this aromatic species produces high and variable amounts of other chemicals that have mostly unknown biological/pharmacological activities. Herein, we have studied the toxicological/pharmacological profile of volatile constituents of a Serbian population of A. annua. Fifty-eight components were identified, among them, artemisia ketone (35.7%), α-pinene (16.5%) and 1,8-cineole (5.5%) were the most abundant ones. Significant variability of A. annua volatile profile was confirmed by means of agglomerative hierarchical cluster analysis indicating the existence of several different A. annua chemotypes. In an attempt to connect the chemical profile of A. annua oil with its biological/toxicological effects, we have evaluated in vivo and/or in vitro toxicity (including hepato- and nephrotoxicity/protection), antinociceptive, antioxidant (DPPH, ABTS and superoxide radical scavenging activity assays), enzyme inhibiting (protein kinase A and α-amylase) and antimicrobial potential of A. annua oil and of its constituents. Our results revealed that the beneficial properties of A. annua botanical drugs are not limited only to their antimalarial properties. Taking into account its relatively low toxicity, the usage of A. annua volatiles (at least of the herein studied population) does not represent a health risk. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Increased Susceptibility to Chemical Toxicity with (Pre-existing ...

    EPA Pesticide Factsheets

    Numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest to risk assessors is the potential for chemicals to interact with pre-existing diseases and aging that may yield cumulative damage, altered chemical response, and increased disease susceptibility. We evaluated the relationships between chemicals and pre-existing disease and identified the type of information needed to evaluate the relationships of interest. This is for presentation at the 54th Society of Toxicology Annual Meeting and ToxExpo 2015.

  7. Probing the ToxCastTM Chemical Library for Predictive Signatures of Developmental Toxicity -NLTO Poster

    EPA Science Inventory

    EPA’s ToxCast™ project is profiling the in vitro bioactivity of chemical compounds to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesize that cell signaling pathways are primary targets for diverse environmental chemicals ...

  8. Probing the ToxCast Chemical Library for Predictive Signatures of Developmental Toxicity

    EPA Science Inventory

    EPA’s ToxCast™ project is profiling the in vitro bioactivity of chemical compounds to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesize that cell signaling pathways are primary targets for diverse environmental chemicals ...

  9. Probing the ToxCastTM Chemical Library for Predictive Signatures of Developmental Toxicity -NLTO Poster

    EPA Science Inventory

    EPA’s ToxCast™ project is profiling the in vitro bioactivity of chemical compounds to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesize that cell signaling pathways are primary targets for diverse environmental chemicals ...

  10. Probing the ToxCast Chemical Library for Predictive Signatures of Developmental Toxicity

    EPA Science Inventory

    EPA’s ToxCast™ project is profiling the in vitro bioactivity of chemical compounds to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesize that cell signaling pathways are primary targets for diverse environmental chemicals ...

  11. Toxic chemical release inventory at the Rocky Flats Environmental Technology Site

    SciTech Connect

    Leonard, R.J.

    1995-07-01

    The Rocky Flats Environmental Technology Site (Site) submits an annual Toxic Chemical Release Inventory (Form R) as required under the Emergency Planning and Community Right-to-Know Act (EPCRA). The Site uses a multi-step process for completing the Form R which includes developing a written procedure, determine thresholds, collection of chemical use and fate information, and peer review.

  12. INVERSE QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP ANALYSIS FOR IMPROVING PREDICTIONS OF CHEMICAL TOXICITY

    EPA Science Inventory

    The toxic outcomes associated with environmental contaminants are often not due to the chemical form that was originally introduced into the environment, but rather to the chemical having undergone a transformation prior to reaching the vulnerable species. More importantly, the c...

  13. THE FUTURE OF TOXICOLOGY-PREDICTIVE TOXICOLOGY: AN EXPANDED VIEW OF CHEMICAL TOXICITY

    EPA Science Inventory

    A chemistry approach to predictive toxicology relies on structure−activity relationship (SAR) modeling to predict biological activity from chemical structure. Such approaches have proven capabilities when applied to well-defined toxicity end points or regions of chemical space. T...

  14. THE FUTURE OF TOXICOLOGY-PREDICTIVE TOXICOLOGY: AN EXPANDED VIEW OF CHEMICAL TOXICITY

    EPA Science Inventory

    A chemistry approach to predictive toxicology relies on structure−activity relationship (SAR) modeling to predict biological activity from chemical structure. Such approaches have proven capabilities when applied to well-defined toxicity end points or regions of chemical space. T...

  15. Proteomic analyses of the environmental toxicity of carcinogenic chemicals

    EPA Science Inventory

    Protein expression and posttranslational modifications consistently change in response to the exposure to environmental chemicals. Recent technological advances in proteomics provide new tools for more efficient characterization of protein expression and posttranslational modific...

  16. Issues Relating To Sediment Toxicity Testing And Bioaccumulation Of Persistent Chemicals In SRS Sediments

    SciTech Connect

    WINONA, SPECHT

    2005-03-01

    Many chemical contaminants that enter a water body in an aqueous form are ultimately deposited to the sediments. Over time, the concentrations of contaminants in sediments may build up to concentrations that are much higher than those found in the water column. However, not all chemicals present in sediments are toxic/bioavailable. Factors that affect bioavailability include aqueous solubility, pH, redox, and composition of the sediment matrix (grain size, mineral constituents, organic matter), and for metals, the quantity of acid volatile sulfides that are present in the sediments. Many sediments contain multiple chemical contaminants, which may interact synergistically or antagonistically with respect to toxicity.

  17. EPA’s ToxCast Program for Predicting Toxicity and Prioritizing Chemicals for Further Screening and Testing

    EPA Science Inventory

    Testing of environmental and industrial chemicals for toxicity potential is a daunting task because of the wide range of possible toxicity mechanisms. Although animal testing is one means of achieving broad toxicity coverage, evaluation of large numbers of chemicals is challengin...

  18. EPA’s ToxCast Program for Predicting Toxicity and Prioritizing Chemicals for Further Screening and Testing

    EPA Science Inventory

    Testing of environmental and industrial chemicals for toxicity potential is a daunting task because of the wide range of possible toxicity mechanisms. Although animal testing is one means of achieving broad toxicity coverage, evaluation of large numbers of chemicals is challengin...

  19. POPs: a QSAR system for developing categories for persistent, bioaccumulative and toxic chemicals and their metabolites.

    PubMed

    Mekenyan, O G; Dimitrov, S D; Pavlov, T S; Veith, G D

    2005-01-01

    This paper presents the framework of a QSAR-based decision support system which provides a rapid screening of potential hazards, classification of chemicals with respect to risk management thresholds, and estimation of missing data for the early stages of risk assessment. At the simplest level, the framework is designed to rank hundreds of chemicals according to their profile of persistence, bioaccumulation potential and toxicity often called the persistent organic pollutant (POP) profile or the PBT (persistent bioaccumulative toxicant) profile. The only input data are the chemical structure. The POPs framework enables decision makers to introduce the risk management thresholds used in the classification of chemicals under various authorities. Finally, the POPs framework advances hazard identification by integrating a metabolic simulator that generates metabolic map for each parent chemical. Both the parent chemicals and plausible metabolites are systematically evaluated for metabolic activation and POPs profile.

  20. Surfactant toxicity to Artemia Franciscana and the influence of humic acid and chemical composition

    PubMed Central

    Deese, Rachel D.; LeBlanc, Madeline R.

    2016-01-01

    Surfactants can be extremely toxic to aquatic species and are introduced to the environment in a variety of ways. It is thus important to understand how other environmental constituents, in this case humic acids (HAs), may alter the toxicity of anthropogenic surfactants. Hatching and mortality assays of Artemia Franciscana were performed for three different toxic surfactants: Triton X-100 (Tx-100, non-ionic), cetylpyridinium chloride (CPC, cationic), and sodium dodecyl sulfate (SDS, anionic). Humic acids of varying composition and concentrations were added to the assays to determine the toxicity mitigating ability of the HAs. Tx-100 had a significant toxic effect on Artemia mortality rates and HAs from terrestrial sources were able to mitigate the toxicity, but an aquatic HA did not. CPC and SDS limited hatching success of the Artemia and, as HAs were added, the hatching percentages increased for all HA sources, indicating toxicity mitigation. In order to determine which functional groups within HAs were responsible for the interaction with the surfactants, the HAs were chemically modified by: (i) bleaching to reduce aromatics, (ii) Soxhlet extraction to reduce lipids, and (iii) acid hydrolysis to reduce O- and N-alkyl groups. Although most of the modified HAs had some toxicity mitigating ability for each of the surfactants, there were two notable differences: 1) the lipid-extracted HA did not reduce the toxicity of Tx-100 and 2) the bleached HA had a lower toxicity mitigating ability for CPC than the other modified HAs. PMID:27453688

  1. A highly toxic morphine-3-glucuronide derivative.

    PubMed

    Salvatella, Mariona; Arsequell, Gemma; Valencia, Gregorio; Rodríguez, Raquel E

    2004-02-23

    By the coupling of octylamine to the uronic acid function of morphine-3-glucuronide (M3G) a new glycoconjugate (morphine-3-octylglucuronamide, M3GOAM) was prepared. When assayed in both rats and mice up to ng/kg (i.p.) doses none of the animals survived. The aliphatic octyl chain may be the lethal factor since a closely related derivative (M3GNH2), was not toxic and showed similar opioid antagonist properties than naloxone.

  2. Toxics Release Inventory Chemical Hazard Information Profiles (TRI-CHIP) Dataset

    EPA Pesticide Factsheets

    The Toxics Release Inventory (TRI) Chemical Hazard Information Profiles (TRI-CHIP) dataset contains hazard information about the chemicals reported in TRI. Users can use this XML-format dataset to create their own databases and hazard analyses of TRI chemicals. The hazard information is compiled from a series of authoritative sources including the Integrated Risk Information System (IRIS). The dataset is provided as a downloadable .zip file that when extracted provides XML files and schemas for the hazard information tables.

  3. Optical disk toxic information online system at Sumitomo Chemical Co. through telecommunication network in Japan

    NASA Astrophysics Data System (ADS)

    Kishida, Fumio; Omodaka, Hisakata; Ishihara, Koichiro; Yamada, Yoshinori; Kato, Hiromi

    Toxicity data about several hundred chemicals, handled and commercialized by Sumitomo Chemical Co., have been collected and estimated. These data are stored in an optical disk filing system "sanfile 8500D". Because the system is mounted with a keyword input panel "Word selecter", information retrieval system is simplified but precised. Online system through telecommunication network is extended between Sumitomo Chemical's works, laboratories, and others. Image informations are mailed from installed facsimili in sanfile 8500D directly.

  4. An enhanced tiered toxicity testing framework with triggers for assessing hazards and risks of commodity chemicals.

    PubMed

    Plunkett, Laura M; Kaplan, A Michael; Becker, Richard A

    2010-12-01

    This paper presents an enhanced integrated testing framework based on tiered testing and endpoint-specific decision triggers envisioned for application to commodity chemical safety assessments. The framework has two tiers in which exposure information can be integrated with hazard data at each Tier. Tier 1 tests are used to screen chemicals for major toxic effects (i.e., acute toxicity potential, target organs of repeat dose toxicity, genotoxicity potential, neurotoxicity potential, reproductive toxicity potential, immunotoxicity potential, and developmental toxicity potential), and to direct planning for more complex and targeted testing in Tier 2. The proposed decision triggers coupled with information on use and potential for exposure allow for scientifically-based decisions to be made about further testing in Tier 2, indicating which specific endpoints and tests warrant further evaluation, and which do not. The testing framework addresses risks to humans during all stages of development and provides data relevant to assessing hazards to sensitive subpopulations, such as infants and children. The REACH program in Europe and TSCA in the United States have led to an increased focus on development of hazard and risk information for chemicals used in industrial processes and consumer products. This framework and its toxicity decision triggers will allow for scientifically justified evaluation of chemicals that is comprehensive in terms of hazard screening, focuses resources on the specific complex tests that are most important for hazard characterization, and minimizes the use of animals. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. Acute toxicity of fire-retardant and foam-suppressant chemicals to yalella azteca (Saussure)

    USGS Publications Warehouse

    McDonald, Susan F.; Hamilton, Steven J.; Buhl, Kevin J.; Heisinger, James F.

    1997-01-01

    Acute toxicity tests were conducted with Hyalella azteca Saussure (an amphipod) exposed in soft and hard waters to three fire retardants (Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F) and two foam suppressants (Phos-Chek WD-881 and Silv-Ex). The chemicals were slightly to moderately toxic to amphipods. The most toxic chemical to amphipods in soft and hard water was Phos-Chek WD-881 (96-h mean lethal concentration [LC50] equal to 10 mg/L and 22 mg/L, respectively), and the least toxic chemical to amphipods in soft water was Fire-Trol GTS-R (96-h LC50 equal to 127 mg/L) and in hard water was Fire-Trol LCG-R (96-h LC50 equal to 535 mg/L). Concentrations of ammonia in tests with the three fire retardants and both water types were greater than reported LC50 values and probably were the major toxic component. Estimated un-ionized ammonia concentrations near the LC50 were frequently less than the reported LC50 ammonia concentrations for amphipods. The three fire retardants were more toxic in soft water than in hard water even though ammonia and un-ionized ammonia concentrations were higher in hard water tests than in soft water tests. The accidental entry of fire-fighting chemicals into aquatic environments could adversely affect aquatic invertebrates, thereby disrupting ecosystem function.

  6. Influence of chemical and environmental stressors on acute cadmium toxicity

    SciTech Connect

    Baer, K.N.; Benson, W.H.

    1987-01-01

    Previous investigations have demonstrated that the cytosolic protein metallothionein (MT) is induced not only by exposure to certain heavy metals but also by a variety of other factors, including environmental stress. While MT synthesis has been observed with exposure to cold temperatures, there is a paucity of data concerning the influence of cold on heavy-metal toxicity. The present investigation focused on the influence of metal and cold pretreatments on the acute toxicity of cadmium. Mortalities of 80% and 100% were observed for mice orally administered challenge doses of 100 mg Cd/kg and 150 mg Cd/kg, respectively. To determine a protective cadmium pretreatment dose, animals were administered 2.5, 5, 10, 20, 25, and 50 mg Cd/kg 24 h prior to cadmium challenge. In animals pretreated with 10 mg Cd/kg, mortalities of 20% and 70% were observed with the respective challenge doses. Immediately following cold stress (4/sup 0/C, 12 h), mortalities of 30% and 90% were observed with cadmium challenge doses of 100 and 150 mg Cd/kg, respectively. Significant correlations were demonstrated between induced hepatic MT concentrations and cadmium pretreatment, as well as cold pretreatment. The induced tolerance to cadmium was attributed, in part, to the induction of MT synthesis. Furthermore, the induced levels of MT resulting from cold stress may confound the simplistic approach of using MT as a biological monitor of occupational exposure to cadmium.

  7. Interactions between toxic chemicals and natural environmental factors--a meta-analysis and case studies.

    PubMed

    Laskowski, Ryszard; Bednarska, Agnieszka J; Kramarz, Paulina E; Loureiro, Susana; Scheil, Volker; Kudłek, Joanna; Holmstrup, Martin

    2010-08-15

    The paper addresses problems arising from effects of natural environmental factors on toxicity of pollutants to organisms. Most studies on interactions between toxicants and natural factors, including those completed in the EU project NoMiracle (Novel Methods for Integrated Risk Assessment of Cumulative Stressors in Europe) described herein, showed that effects of toxic chemicals on organisms can differ vastly depending purely on external conditions. We compiled data from 61 studies on effects of temperature, moisture and dissolved oxygen on toxicity of a range of chemicals representing pesticides, polycyclic aromatic hydrocarbons, plant protection products of bacterial origin and trace metals. In 62.3% cases significant interactions (p< or =0.05 or less) between natural factors and chemicals were found, reaching 100% for the effect of dissolved oxygen on toxicity of waterborne chemicals. The meta-analysis of the 61 studies showed that the null hypothesis assuming no interactions between toxic chemicals and natural environmental factors should be rejected at p=2.7 x 10(-82) (truncated product method probability). In a few cases of more complex experimental designs, also second-order interactions were found, indicating that natural factors can modify interactions among chemicals. Such data emphasize the necessity of including information on natural factors and their variation in time and across geographic regions in ecological risk assessment. This can be done only if appropriate ecotoxicological test designs are used, in which test organisms are exposed to toxicants at a range of environmental conditions. We advocate designing such tests for the second-tier ecological risk assessment procedures.

  8. Chemical characterization and toxicity of particulate matter emissions from roadside trash combustion in urban India

    NASA Astrophysics Data System (ADS)

    Vreeland, Heidi; Schauer, James J.; Russell, Armistead G.; Marshall, Julian D.; Fushimi, Akihiro; Jain, Grishma; Sethuraman, Karthik; Verma, Vishal; Tripathi, Sachi N.; Bergin, Michael H.

    2016-12-01

    Roadside trash burning is largely unexamined as a factor that influences air quality, radiative forcing, and human health even though it is ubiquitously practiced across many global regions, including throughout India. The objective of this research is to examine characteristics and redox activity of fine particulate matter (PM2.5) associated with roadside trash burning in Bangalore, India. Emissions from smoldering and flaming roadside trash piles (n = 24) were analyzed for organic and elemental carbon (OC/EC), brown carbon (BrC), and toxicity (i.e. redox activity, measured via the dithiothreitol "DTT" assay). A subset of samples (n = 8) were further assessed for toxicity by a cellular assay (macrophage assay) and also analyzed for trace organic compounds. Results show high variability of chemical composition and toxicity between trash-burning emissions, and characteristic differences from ambient samples. OC/EC ratios for trash-burning emissions range from 0.8 to 1500, while ambient OC/EC ratios were observed at 5.4 ± 1.8. Trace organic compound analyses indicate that emissions from trash-burning piles were frequently composed of aromatic di-acids (likely from burning plastics) and levoglucosan (an indicator of biomass burning), while the ambient sample showed high response from alkanes indicating notable representation from vehicular exhaust. Volume-normalized DTT results (i.e., redox activity normalized by the volume of air pulled through the filter during sampling) were, unsurprisingly, extremely elevated in all trash-burning samples. Interestingly, DTT results suggest that on a per-mass basis, fresh trash-burning emissions are an order of magnitude less redox-active than ambient air (13.4 ± 14.8 pmol/min/μgOC for trash burning; 107 ± 25 pmol/min/μgOC for ambient). However, overall results indicate that near trash-burning sources, exposure to redox-active PM can be extremely high.

  9. Food safety. [chemical contaminants and human toxic diseases

    NASA Technical Reports Server (NTRS)

    Pier, S. M.; Valentine, J. L.

    1975-01-01

    Illness induced by unsafe food is a problem of great public health significance. This study relates exclusively to the occurrence of chemical agents which will result in food unsafe for human consumption since the matter of food safety is of paramount importance in the mission and operation of the manned spacecraft program of the National Aeronautics and Space Administration.

  10. The Toxicity Data Landscape for Environmental Chemicals (journal)

    EPA Science Inventory

    Thousands of chemicals are in common use but only a portion of them have undergone significant toxicological evaluation, leading to the need to prioritize the remainder for targeted testing. To address this issue, the U.S. Environmental Protection Agency (U.S. EPA) and other orga...

  11. Predicting modes of toxic action from chemical structure

    EPA Science Inventory

    Like many of the papers in the ET&C top 100 list, the development of the fathead minnow database and the assignment of modes of action to the 617 chemicals therein was the result of a comprehensive research effort by a multidisciplinary team of researchers with expertise in quant...

  12. The Toxicity Data Landscape for Environmental Chemicals (journal)

    EPA Science Inventory

    Thousands of chemicals are in common use but only a portion of them have undergone significant toxicological evaluation, leading to the need to prioritize the remainder for targeted testing. To address this issue, the U.S. Environmental Protection Agency (U.S. EPA) and other orga...

  13. Exposure Considerations for Chemical Prioritization and Toxicity Testing

    EPA Science Inventory

    Globally there is a need to characterize potential risk to human health and the environment that arises from the manufacture and use of tens of thousands of chemicals. Currently, a significant research effort is underway to apply new technologies to screen and prioritize chemica...

  14. Predicting modes of toxic action from chemical structure

    EPA Science Inventory

    Like many of the papers in the ET&C top 100 list, the development of the fathead minnow database and the assignment of modes of action to the 617 chemicals therein was the result of a comprehensive research effort by a multidisciplinary team of researchers with expertise in quant...

  15. Chemical modification : a non-toxic approach to wood preservation

    Treesearch

    Roger M. Rowell

    2005-01-01

    Reaction of wood with anhydrides, isocyanates, and epoxides reduces the moisture content of the cell wall and increases the resistance of the modified wood to attack by fungi. As the level of bonded chemical increases. the cell wall equilibrium moisture content decreases and the resistance to attack by white-and brown-rot fungi increases. There is a direct relationship...

  16. The Virtual Liver: Modeling Chemical-Induced Liver Toxicity

    EPA Science Inventory

    The US EPA Virtual Liver (v-Liver) project is aimed at modeling chemical-induced processes in hepatotoxicity and simulating their dose-dependent perturbations. The v-Liver embodies an emerging field of research in computational tissue modeling that integrates molecular and cellul...

  17. The Virtual Liver: Modeling Chemical-Induced Liver Toxicity

    EPA Science Inventory

    The US EPA Virtual Liver (v-Liver) project is aimed at modeling chemical-induced processes in hepatotoxicity and simulating their dose-dependent perturbations. The v-Liver embodies an emerging field of research in computational tissue modeling that integrates molecular and cellul...

  18. Exposure Considerations for Chemical Prioritization and Toxicity Testing

    EPA Science Inventory

    Globally there is a need to characterize potential risk to human health and the environment that arises from the manufacture and use of tens of thousands of chemicals. Currently, a significant research effort is underway to apply new technologies to screen and prioritize chemica...

  19. Prediction of Chemical Carcinogenicity in Rodents from in vitro Genetic Toxicity Assays

    NASA Astrophysics Data System (ADS)

    Tennant, Raymond W.; Margolin, Barry H.; Shelby, Michael D.; Zeiger, Errol; Haseman, Joseph K.; Spalding, Judson; Caspary, William; Resnick, Michael; Stasiewicz, Stanley; Anderson, Beth; Minor, Robert

    1987-05-01

    carcinogenicity and the four in vitro STTs to attempt to confirm the current findings. The standard against which the performance of STTs is measured has changed dramatically in the past decade. The high levels of concordance published in the early 1970s were accurate at the time. Nearly all known carcinogens tested were genotoxic, and there was little experimental evidence on which to base a judgment of noncarcinogenicity which, taken together, restricted assessment of test performances with noncarcinogens. With the increasing availability of results from NCI and NTP 2-year carcinogenicity studies in rodents, higher frequencies of nongenotoxic carcinogens and genotoxic noncarcinogens have been observed; this has resulted in the reduced concordance of the STT results with carcinogenicity results. It is clear that even with a battery of assays, not all rodent carcinogens are in vitro mutagens nor are all in vitro mutagens rodent carcinogens. If current in vitro STTs are expected to replace long-term rodent studies for the identification of chemical carcinogens, then that expectation should be abandoned. STTs do, however, continue to offer an economical, rapid, and dependable means to detect genotoxic chemicals. There is a range of applications in which STTs have been used successfully, from the identification of mutagenic fractions in complex mixtures such as cooked meat (32, 33) or air pollutants (34) to the early identification of genetic toxicity in the development of new chemical products (35). Requirements for the use of STT have not been consistent in both the national and international regulatory agencies. This is evident in the variety of testing requirements (8) and the different impacts that positive test results have on the registration or further testing requirements of chemicals. Consensus on these matters is not likely to occur in the near future, but agreement should be possible in certain areas. For instance, any time a new test or strategy is proposed, it is

  20. Linear solvation energy relationships for toxicity of selected organic chemicals to Daphnia pulex and Daphnia magna

    USGS Publications Warehouse

    Passino, Dora R.M.; Hickey, James P.; Frank, Anthony M.

    1988-01-01

    In the Laurentian Great Lakes, more than 300 contaminants have been identified in fish, other biota, water, and sediment. Current hazard assessment of these chemicals by the National Fisheries Research Center-Great Lakes is based on their toxicity, occurrence in the environment, and source. Although scientists at the Center have tested over 70 chemicals with the crustacean Daphnia pulex, the number of experimental data needed to screen the huge array of chemicals in the Great Lakes exceeds the practical capabilities of conducting bioassays. This limitation can be partly circumvented, however, by using mathematical models based on quantitative structure-activity relationships (QSAR) to provide rapid, inexpensive estimates of toxicity. Many properties of chemicals, including toxicity, bioaccumulation and water solubility are well correlated and can be predicted by equations of the generalized linear solvation energy relationships (LSER). The equation we used to model solute toxicity is Toxicity = constant + mVI/100 + s (π* + dδ) + bβm + aαm where VI = intrinsic (Van der Waals) molar volume; π* = molecular dipolarity/polarizability; δ = polarizability 'correction term'; βm = solute hydrogen bond acceptor basicity; and αm = solute hydrogen bond donor acidity. The subscript m designates solute monomer values for α and β. We applied the LSER model to 48-h acute toxicity data (measured as immobilization) for six classes of chemicals detected in Great Lakes fish. The following regression was obtained for Daphnia pulex (concentration = μM): log EC50 = 4.86 - 4.35 VI/100; N = 38, r2 = 0.867, sd = 0.403 We also used the LSER modeling approach to analyze to a large published data set of 24-h acute toxicity for Daphnia magna; the following regression resulted, for eight classes of compounds (concentration = mM): log EC50 = 3.88 - 4.52 VI/100 - 1.62 π* + 1.66 βm - 0.916 αm; N = 62, r2 = 0.859, sd = 0.375 In addition we developed computer software that identifies

  1. High throughput vacuum chemical epitaxy

    NASA Astrophysics Data System (ADS)

    Fraas, L. M.; Malocsay, E.; Sundaram, V.; Baird, R. W.; Mao, B. Y.; Lee, G. Y.

    1990-10-01

    We have developed a vacuum chemical epitaxy (VCE) reactor which avoids the use of arsine and allows multiple wafers to be coated at one time. Our vacuum chemical epitaxy reactor closely resembles a molecular beam epitaxy system in that wafers are loaded into a stainless steel vacuum chamber through a load chamber. Also as in MBE, arsenic vapors are supplied as reactant by heating solid arsenic sources thereby avoiding the use of arsine. However, in our VCE reactor, a large number of wafers are coated at one time in a vacuum system by the substitution of Group III alkyl sources for the elemental metal sources traditionally used in MBE. Higher wafer throughput results because in VCE, the metal-alkyl sources for Ga, Al, and dopants can be mixed at room temperature and distributed uniformly though a large area injector to multiple substrates as a homogeneous array of mixed element molecular beams. The VCE reactor that we have built and that we shall describe here uniformly deposits films on 7 inch diameter substrate platters. Each platter contains seven two inch or three 3 inch diameter wafers. The load chamber contains up to nine platters. The vacuum chamber is equipped with two VCE growth zones and two arsenic ovens, one per growth zone. Finally, each oven has a 1 kg arsenic capacity. As of this writing, mirror smooth GaAs films have been grown at up to 4 μm/h growth rate on multiple wafers with good thickness uniformity. The background doping is p-type with a typical hole concentration and mobility of 1 × 10 16/cm 3 and 350 cm 2/V·s. This background doping level is low enough for the fabrication of MESFETs, solar cells, and photocathodes as well as other types of devices. We have fabricated MESFET devices using VCE-grown epi wafers with peak extrinsic transconductance as high as 210 mS/mm for a threshold voltage of - 3 V and a 0.6 μm gate length. We have also recently grown AlGaAs epi layers with up to 80% aluminum using TEAl as the aluminum alkyl source. The Al

  2. Perspectives on Validation of High-Throughput Assays Supporting 21st Century Toxicity Testing

    EPA Science Inventory

    In vitro high-throughput screening (HTS) assays are seeing increasing use in toxicity testing. HTS assays can simultaneously test many chemicals but have seen limited use in the regulatory arena, in part because of the need to undergo rigorous, time-consuming formal validation. ...

  3. Perspectives on Validation of High-Throughput Assays Supporting 21st Century Toxicity Testing

    EPA Science Inventory

    In vitro high-throughput screening (HTS) assays are seeing increasing use in toxicity testing. HTS assays can simultaneously test many chemicals but have seen limited use in the regulatory arena, in part because of the need to undergo rigorous, time-consuming formal validation. ...

  4. Comparative Toxicity of Eight Oil Dispersants, Louisiana Sweet Crude Oil (LSC) and Chemically Dispersed LSC to Two Aquatic Test Species

    EPA Science Inventory

    This study describes the acute toxicity of eight commercial oil dispersants, Louisiana sweet crude oil (LSC), and chemically dispersed LSC. The approach utilized consistent test methodologies within a single laboratory in assessing the relative acute toxicity of the eight dispers...

  5. Comparative Toxicity of Eight Oil Dispersants, Louisiana Sweet Crude Oil (LSC) and Chemically Dispersed LSC to Two Aquatic Test Species

    EPA Science Inventory

    This study describes the acute toxicity of eight commercial oil dispersants, Louisiana sweet crude oil (LSC), and chemically dispersed LSC. The approach utilized consistent test methodologies within a single laboratory in assessing the relative acute toxicity of the eight dispers...

  6. Effective Strategies for Monitoring and Regulating Chemical Mixtures and Contaminants Sharing Pathways of Toxicity

    PubMed Central

    Venkatesan, Arjun K.; Halden, Rolf U.

    2015-01-01

    Traditionally, hazardous chemicals have been regulated in the U.S. on a one-by-one basis, an approach that is slow, expensive and can be inefficient, as illustrated by a decades-long succession of replacing one type of organohalogen flame retardants (OHFRs) with another one, without addressing the root cause of toxicity and associated public health threats posed. The present article expounds on the need for efficient monitoring strategies and pragmatic steps in reducing environmental pollution and adverse human health impacts. A promising approach is to combine specific bioassays with state-of-the-art chemical screening to identify chemicals and chemical mixtures sharing specific modes of action (MOAs) and pathways of toxicity (PoTs). This approach could be used to identify and regulate hazardous chemicals as classes or compound families, featuring similar biological end-points, such as endocrine disruption and mutagenicity. Opportunities and potential obstacles of implementing this approach are discussed. PMID:26343697

  7. Chemical structure indexing of toxicity data on the internet: moving toward a flat world.

    PubMed

    Richard, Ann M; Gold, Lois Swirsky; Nicklaus, Marc C

    2006-05-01

    Standardized chemical structure annotation of public toxicity databases and information resources is playing an increasingly important role in the 'flattening' and integration of diverse sets of biological activity data on the Internet. This review discusses public initiatives that are accelerating the pace of this transformation, with particular reference to toxicology-related chemical information. Chemical content annotators, structure locator services, large structure/data aggregator web sites, structure browsers, International Union of Pure and Applied Chemistry (IUPAC) International Chemical Identifier (InChI) codes, toxicity data models and public chemical/biological activity profiling initiatives are all playing a role in overcoming barriers to the integration of toxicity data, and are bringing researchers closer to the reality of a mineable chemical Semantic Web. An example of this integration of data is provided by the collaboration among researchers involved with the Distributed Structure-Searchable Toxicity (DSSTox) project, the Carcinogenic Potency Project, projects at the National Cancer Institute and the PubChem database.

  8. In silico prediction of chemical toxicity profile using local lazy learning.

    PubMed

    Lu, Jing; Zhang, Pin; Zou, Xiaowen; Zhao, Xiaoqiang; Cheng, Keguang; Zhao, Yilei; Bi, Yi; Zheng, Mingyue; Luo, Xiaomin

    2017-02-17

    Chemical toxicity is an important reason for late-stage failure in drug R&D. However, it is time-consuming and expensive to identify the multiple toxicities of compounds using the traditional experiments. Thus, it is attractive to build an accurate prediction model for the toxicity profile of compounds. In this study, we carried out a research on six types of toxicities: (I) Acute Toxicity; (II) Mutagenicity; (III) Tumorigenicity; (IV) Skin and Eye Irritation; (V) Reproductive Effects; (VI) Multiple Dose Effects, using local lazy learning (LLL) method for multi-label learning. 17,120 compounds were split into the training set and the test set as a ratio of 4:1 by using the Kennard-Stone algorithm. Four types of properties, including molecular fingerprints (ECFP_4 and FCFP_4), descriptors, and chemical-chemical-interactions, were adopted for model building. The model 'ECFP_4+LLL' yielded the best performance for the test set, while balanced accuracy (BACC) reached 0.692, 0.691, 0.666, 0.680, 0.631, 0.599 for six types of toxicities, respectively. Furthermore, the prediction ability of the 'ECFP_4+LLL' model was tested and verified by two external sets. Finally, some essential toxicophores for six types of toxicities were identified by using the Laplacian-modified Bayesian model. We wish that the accurate prediction model and the chemical toxicophores can provide some guidance for designing drugs with lower toxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Toxicity induced by chemical warfare agents: insights on the protective role of melatonin.

    PubMed

    Pita, René; Marco-Contelles, José; Ramos, Eva; Del Pino, Javier; Romero, Alejandro

    2013-11-25

    Chemical Warfare Agents (CWAs) are substances that can be used to kill, injure or incapacitate an enemy in warfare, but also against civilian population in terrorist attacks. Many chemical agents are able to generate free radicals and derived reactants, excitotoxicity process, or inflammation, and as consequence they can cause neurological symptoms and damage in different organs. Nowadays, taking into account that total immediate decontamination after exposure is difficult to achieve and there are not completely effective antidotes and treatments against all CWAs, we advance and propose that medical countermeasures against CWAs poisoning would benefit from a broad-spectrum multipotent molecule. Melatonin, a versatile and ubiquitous antioxidant molecule, originally discovered as a hormone synthesized mainly in the pineal gland, has low toxicity and high efficacy in reducing oxidative damage, anti-inflammatory effects by regulation of multiple cellular pathways and properties to prevent excitotoxicity, among others. The purpose of this review is to show the multiple and diverse properties of melatonin, as a pleiotropic indole derivative, and its marked potential for improving human health against the most widely used chemical weapons.

  10. Toxic Industrial Chemical Removal by Isostructural Metal-Organic Frameworks

    DTIC Science & Technology

    2011-01-01

    distance between the MOF -74 metal and the adsorbed hydrogen molecule. In addition, the authors studied the methane storage capabilities of these MOFs and...industrial processes such as gas storage , separations, and catalysis [1-4]. MOFs self-assemble using combinations of metal clusters and organic linking...and organic linkers to achieve better selectivity and activity towards chemicals such as, hydrogen , carbon dioxide, and methane, for gas storage

  11. Assessing physiological .response to toxic industrial chemical exposure in megacities

    DTIC Science & Technology

    2016-03-05

    Rai, A. (2011). DNA damage and cholinesterase activity in occupational workers exposed to pesticides . Environmental Toxicology and Pharmacology, 31(2...chemicals and environmental hazards unique to the megacity operational environment . Properly validated biomarkers of exposure and effect can integrate...Center for Environmental Health Research REPORT NUMBER 568 Doughten Drive Fort Detrick, MD 2 1702-50 l 0 16-047 9. SPONSORING/MONITORING AGENCY NAME

  12. Stabilization of microorganisms for in situ degradation of toxic chemicals

    SciTech Connect

    Crawford, R.L.; Stormo, K.

    1990-01-01

    In our initial work, we have developed methods to microencapsulate cells within beads of 5--100,{mu}m diameter, and we have examined these entrapped cells for their abilities to mineralize specific chemicals in the presence of subsurface soils and waters obtained from the University of Idaho Groundwater Research Site (GRS). We have employed a pentachlorophenol (PCP)-degrading Flavobacterium and a toluene-degrading Pseudomonas. Cells were immobilized within one of three polymeric matrixes: alginate, agarose, or polyurethane.

  13. Anti-obesity activity, acute toxicity, and chemical constituents of aqueous and ethanol Viola mandshurica extracts.

    PubMed

    Sung, Yoon-Young; Kim, Dong-Seon; Kim, Seung-Hyung; Kim, Ho Kyoung

    2017-06-06

    Viola mandshurica has traditionally been used as an expectorant, diuretic, and anti-inflammatory drug. The present study was designed to test the hypothesis that low doses of two different V. mandshurica extracts have anti-obesity effects. We evaluated the effects of ethanol extract (VME) and aqueous extract (VMA) from V. mandshurica on high-fat diet (HFD)-induced obese mice as well as the acute oral toxicities and chemical compositions of both extracts. Oral administration of VME or VMA (50, 100, or 200 mg/kg) decreased body weight gain, liver and adipose tissue mass, adipocyte size, and serum lipid levels. Both extracts increased adiponectin serum concentrations and mRNA expression in epididymal adipose tissue. VME and VMA also reversed the HFD-induced mRNA expression of lipogenic genes such as CCAAT/enhancer binding protein (C/EBP)α, C/EBPβ, sterol regulatory element-binding protein 1c, and leptin in adipose tissue, whereas they increased mRNA expression of uncoupling protein 2 and adenosine monophosphate-activated protein kinase (AMPK). VME and VMA increased the phosphorylation of AMPK and acetyl-coA carboxylase with a concomitant decrease in fat accumulation in the liver. High performance liquid chromatography analysis revealed that both VME and VMA contained esculetin (0.566% for VME, 0.231% for VMA) and schaftoside (0.147% for VME, 0.126% for VMA). In a 2-week acute toxicity study, administration of a single oral dose of VME or VMA (5000 mg/kg) caused no signs of toxicity or mortality. These results suggest that both VM extracts exert anti-obesity effects in HFD-induced obese mice by suppressing lipogenesis and activating AMPK in the liver and adipose tissue. Our findings suggest that VM extracts could be a safe and effective treatment for obesity.

  14. Direct chemical oxidation of mixed or toxic wastes

    SciTech Connect

    Balazs, G B; Cooper, J F; Farmer, J C; Lewis, P

    1999-05-01

    Direct Chemical Oxidation (DCO) is an ambient-pressure, low-temperature (<100 C), and aqueous-based process for general-purpose destruction of the organic fraction of hazardous or mixed waste. It uses the peroxydisulfate anion (S{sub 2}O{sub 8}{sup 2{minus}}) in acid or base solutions. The byproduct of the oxidation reaction, typically sodium or ammonium hydrogen sulfate, may be recycled electrolytically to produce the oxidant. The oxidation kinetic reaction is first order with respect to the peroxydisulfate concentration, expressed in equivalents. The rate constant is constant for nearly all dissolved organic compounds: k{sub a} = 0.01 {+-} 0.005 min{sup {minus}1}. This reflects a common rate-determining step, which is the decomposition of the peroxydisulfate anion into the chemically active derivative, the sulfate radical anion, SO{sub 4}{sup {minus}}. This decomposition is promoted in DCO by raising the operating temperature into the range of 80-100 C. Rates are given for approximately 30 substances with diverse functional groups at low concentrations, and for a number of solid and liquid wastes typical of nuclear and chemical industries. The process has been scale up for treatment studies on chlorinated hydrocarbons, in which the hydrolysis of solvent mixtures was followed by oxidation of products in a series of stirred tank reactors. Cost estimates, safety considerations, and a comprehensive bibliography are given.

  15. Controlling Cellular Uptake and Toxicity of Polyphenylene Dendrimers by Chemical Functionalization.

    PubMed

    Hammer, Brenton; Wu, Yuzhou; Fischer, Stephan; Liu, Weina; Weil, Tanja; Müllen, Klaus

    2017-02-21

    Polyphenylene dendrimers (PPDs) represent a unique class of macromolecules based on their monodisperse and shape-persistent nature. These characteristics have enabled the synthesis of a new genre of "patched" surface dendrimers where their exterior can be functionalized with a variety of polar and unpolar substituents to yield lipophilic binding sites in a site-specific way. While such materials have proven capable of complexing biologically relevant molecules, shown high cellular uptake in various cell lines, and low to no toxicity; there is minimal understanding of the driving forces to these characteristics. Therefore, the present work aims at investigating whether it is the specific chemical functionalities, relative quantities of each moiety, or the "patched" surface patterning on the dendrimers that more significantly influences their behavior in biological media.

  16. Acute oral toxicity of chemicals in terrestrial life stages of amphibians: Comparisons to birds and mammals.

    PubMed

    Crane, Mark; Finnegan, Meaghean; Weltje, Lennart; Kosmala-Grzechnik, Sylwia; Gross, Melanie; Wheeler, James R

    2016-10-01

    Amphibians are currently the most threatened and rapidly declining group of vertebrates and this has raised concerns about their potential sensitivity and exposure to plant protection products and other chemicals. Current environmental risk assessment procedures rely on surrogate species (e.g. fish and birds) to cover the risk to aquatic and terrestrial life stages of amphibians, respectively. Whilst a recent meta-analysis has shown that in most cases amphibian aquatic life stages are less sensitive to chemicals than fish, little research has been conducted on the comparative sensitivity of terrestrial amphibian life stages. Therefore, in this paper we address the questions "What is the relative sensitivity of terrestrial amphibian life stages to acute chemical oral exposure when compared with mammals and birds?" and "Are there correlations between oral toxicity data for amphibians and data for mammals or birds?" Identifying a relationship between these data may help to avoid additional vertebrate testing. Acute oral amphibian toxicity data collected from the scientific literature and ecotoxicological databases were compared with toxicity data for mammals and birds. Toxicity data for terrestrial amphibian life stages are generally sparse, as noted in previous reviews. Single-dose oral toxicity data for terrestrial amphibian life stages were available for 26 chemicals and these were positively correlated with LD50 values for mammals, while no correlation was found for birds. Further, the data suggest that oral toxicity to terrestrial amphibian life stages is similar to or lower than that for mammals and birds, with a few exceptions. Thus, mammals or birds are considered adequate toxicity surrogates for use in the assessment of the oral exposure route in amphibians. However, there is a need for further data on a wider range of chemicals to explore the wider applicability of the current analyses and recommendations. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Dissecting the assays to assess microbial tolerance to toxic chemicals in bioprocessing.

    PubMed

    Zingaro, Kyle A; Nicolaou, Sergios A; Papoutsakis, Eleftherios T

    2013-11-01

    Microbial strains are increasingly used for the industrial production of chemicals and biofuels, but the toxicity of components in the feedstock and product streams limits process outputs. Selected or engineered microbes that thrive in the presence of toxic chemicals can be assessed using tolerance assays. Such assays must reasonably represent the conditions the cells will experience during the intended process and measure the appropriate physiological trait for the desired application. We review currently used tolerance assays, and examine the many parameters that affect assay outcomes. We identify and suggest the use of the best-suited assays for each industrial bioreactor operating condition, discuss next-generation assays, and propose a standardized approach for using assays to examine tolerance to toxic chemicals. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Fluorescence-based assay as a new screening tool for toxic chemicals

    PubMed Central

    Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

    2016-01-01

    Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients. PMID:27653274

  19. Fluorescence-based assay as a new screening tool for toxic chemicals

    NASA Astrophysics Data System (ADS)

    Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

    2016-09-01

    Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

  20. Fluorescence-based assay as a new screening tool for toxic chemicals.

    PubMed

    Moczko, Ewa; Mirkes, Evgeny M; Cáceres, César; Gorban, Alexander N; Piletsky, Sergey

    2016-09-22

    Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

  1. The ChemScreen project to design a pragmatic alternative approach to predict reproductive toxicity of chemicals.

    PubMed

    van der Burg, Bart; Wedebye, Eva Bay; Dietrich, Daniel R; Jaworska, Joanna; Mangelsdorf, Inge; Paune, Eduard; Schwarz, Michael; Piersma, Aldert H; Kroese, E Dinant

    2015-08-01

    There is a great need for rapid testing strategies for reproductive toxicity testing, avoiding animal use. The EU Framework program 7 project ChemScreen aimed to fill this gap in a pragmatic manner preferably using validated existing tools and place them in an innovative alternative testing strategy. In our approach we combined knowledge on critical processes affected by reproductive toxicants with knowledge on the mechanistic basis of such effects. We used in silico methods for prescreening chemicals for relevant toxic effects aiming at reduced testing needs. For those chemicals that need testing we have set up an in vitro screening panel that includes mechanistic high throughput methods and lower throughput assays that measure more integrative endpoints. In silico pharmacokinetic modules were developed for rapid exposure predictions via diverse exposure routes. These modules to match in vitro and in vivo exposure levels greatly improved predictivity of the in vitro tests. As a further step, we have generated examples how to predict reproductive toxicity of chemicals using available data. We have executed formal validations of panel constituents and also used more innovative manners to validate the test panel using mechanistic approaches. We are actively engaged in promoting regulatory acceptance of the tools developed as an essential step towards practical application, including case studies for read-across purposes. With this approach, a significant saving in animal use and associated costs seems very feasible. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Accelerated hematopoietic toxicity by high energy (56)Fe radiation.

    PubMed

    Datta, Kamal; Suman, Shubhankar; Trani, Daniela; Doiron, Kathryn; Rotolo, Jimmy A; Kallakury, Bhaskar V S; Kolesnick, Richard; Cole, Michael F; Fornace, Albert J

    2012-03-01

    There is little information on the relative toxicity of highly charged (Z) high-energy (HZE) radiation in animal models compared to γ or X-rays, and the general assumption based on in vitro studies has been that acute toxicity is substantially greater. C57BL/6J mice were irradiated with (56)Fe ions (1 GeV/nucleon), and acute (within 30 d) toxicity compared to that of γ rays or protons (1 GeV). To assess relative hematopoietic and gastrointestinal toxicity, the effects of (56)Fe ions were compared to γ rays using complete blood count (CBC), bone marrow granulocyte-macrophage colony forming unit (GM-CFU), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis in bone marrow, and intestinal crypt survival. Although onset was more rapid, (56)Fe ions were only slightly more toxic than γ rays or protons with lethal dose (LD)(50/30) (a radiation dose at which 50% lethality occurs at 30-day) values of 5.8, 7.25, and 6.8 Gy, respectively, with relative biologic effectiveness for (56)Fe ions of 1.25 and 1.06 for protons. (56)Fe radiation caused accelerated and more severe hematopoietic toxicity. Early mortality correlated with more profound leukopenia and subsequent sepsis. Results indicate that there is selective enhanced toxicity to bone marrow progenitor cells, which are typically resistant to γ rays, and bone marrow stem cells, because intestinal crypt cells did not show increased HZE toxicity.

  3. In silico quantitative structure toxicity relationship of chemical compounds: some case studies.

    PubMed

    Deeb, Omar; Goodarzi, Mohammad

    2012-09-01

    Undesirable toxicity is still a major block in the drug discovery process. Obviously, capable techniques that identify poor effects at a very early stage of product development and provide reasonable toxicity estimates for the huge number of untested compounds are needed. In silico techniques are very useful for this purpose, because of their advantage in reducing time and cost. These case studies give the description of in silico validation techniques and applied modeling methods for the prediction of toxicity of chemical compounds. In silico toxicity prediction techniques can be classified into two categories: Molecular Modeling and methods that derive predictions from experimental data. Molecular modeling is a computational approach to mimic the behavior of molecules, from small molecules (e.g. in conformational analysis) to biomolecules. But the same approaches can also be applied for toxicological purposes, if the mechanism is receptor mediated. Quantitative Structure-Toxicity Relationships (QSTRs) models are typical examples for the prediction of toxicity which relates variations in the molecular structures to toxicity. There are many applied modeling techniques in QSTR such as Partial Least Squares, Artificial Neural Networks, and Principal Component Regression (PCR). The applicability of these techniques in predictive toxicology will be discussed with different examples of sets of chemical compounds.

  4. 1997 toxic chemical release inventory -- Emergency Planning and Community Right-To-Know Act, Section 313

    SciTech Connect

    Zaloudek, D.E.

    1998-06-30

    Two listed toxic chemicals were used at the Hanford Site above established activity thresholds: phosphoric acid and chlorine. Because total combined quantities of chlorine released, disposed, treated, recovered through recycle operations, co-combusted for energy recovery, and transferred to off-site locations for the purpose of recycle, energy recovery, treatment, and/or disposal, amounted to less than 500 pounds, the Hanford Site qualified for the alternate one million pound threshold for chlorine. Accordingly, this Toxic Chemical Release Inventory includes a Form A for chlorine, and a Form B for phosphoric acid.

  5. Development and evaluation of multispecies test protocols for assessing chemical toxicity

    SciTech Connect

    Garten, C.T. Jr.; Suter, G.W. II; Blaylock, B.G.

    1985-06-01

    Toxicity testing is a well-recognized tool to assist in evaluating the hazards of chemicals to individual biological species. Multispecies toxicity tests, however, are now well developed. Three test systems were examined: the legume-Rhizobium symbiosis for N-fixation, soil microbial populations, and algal multispecies interactions. Test protocols were to be developed and tested using several different chemicals. Test protocols for the legume-Rhizobium and soil microorganisms systems were developed and are presented. The algal multispecies system will require more research, and thus no protocol was recommended at this time. Separate abstracts were prepared for each test system. (ACR)

  6. Comparative toxicity of eight oil dispersants, Louisiana sweet crude oil (LSC), and chemically dispersed LSC to two aquatic test species.

    PubMed

    Hemmer, Michael J; Barron, Mace G; Greene, Richard M

    2011-10-01

    The present study describes the acute toxicity of eight commercial oil dispersants, South Louisiana sweet crude oil (LSC), and chemically dispersed LSC. The approach used consistent test methodologies within a single laboratory in assessing the relative acute toxicity of the eight dispersants, including Corexit 9500A, the predominant dispersant applied during the DeepWater Horizon spill in the Gulf of Mexico. Static acute toxicity tests were performed using two Gulf of Mexico estuarine test species, the mysid shrimp (Americamysis bahia) and the inland silversides (Menidia beryllina). Dispersant-only test solutions were prepared with high-energy mixing, whereas water-accommodated fractions of LSC and chemically dispersed LSC were prepared with moderate energy followed by settling and testing of the aqueous phase. The median lethal concentration (LC50) values for the dispersant-only tests were calculated using nominal concentrations, whereas tests conducted with LSC alone and dispersed LSC were based on measured total petroleum hydrocarbon (TPH) concentrations. For all eight dispersants in both test species, the dispersants alone were less toxic (LC50s: 2.9 to >5,600 µl/L) than the dispersant-LSC mixtures (0.4-13 mg TPH/L). Louisiana sweet crude oil alone had generally similar toxicity to A. bahia (LC50: 2.7 mg TPH/L) and M. beryllina (LC50: 3.5 mg TPH/L) as the dispersant-LSC mixtures. The results of the present study indicate that Corexit 9500A had generally similar toxicity to other available dispersants when tested alone but was generally less toxic as a mixture with LSC.

  7. Are antifouling paint particles a continuous source of toxic chemicals to the marine environment?

    PubMed

    Soroldoni, Sanye; Abreu, Fiamma; Castro, Ítalo Braga; Duarte, Fabio Andrei; Pinho, Grasiela Lopes Leães

    2017-05-15

    Antifouling paint particles (APPs) are generated during periodical maintenance of boat hulls. Chemical composition and toxicity (either chronic or acute) of APPs found in the sediment was evaluated using the epibenthic copepod Nitokra sp. The APPs analyzed showed the presence of high levels of metals such as Cu (234,247±268μgg(-1)), Zn (112,404±845μgg(-1)) and the booster biocide DCOIT (0.13μgg(-1)). Even at low concentrations (as from 5mgg(-1) of APPs by mass of sediment) a significantly decrease in the fecundity was observed in laboratory tests. When the sediment was disturbed in elutriate test, a LC50 of 0.14% for APPs was found. This study was the first assessment of toxicity associated with the presence of APPs in sediment to benthic organisms, and it calls attention to the need of improving regulations in boatyards and marina areas. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Chemical degradation and toxicity reduction of 4-chlorophenol in different matrices by gamma-ray treatment

    NASA Astrophysics Data System (ADS)

    Kang, Sung-Wook; Shim, Seung-Bo; Park, Young-Kwon; Jung, Jinho

    2011-03-01

    Gamma-ray treatment of 4-chlorophenol (4-CP) in different matrices was studied in terms of both chemical degradation and toxicity reduction. Degradation of 4-CP in a complex effluent matrix was less efficient than that in ultrapure water. This is most likely due to the consumption of reactive radicals by matrix components, such as dissolved organic matter in effluents. The matrix effect caused much more profound changes in toxicity. Gamma-ray treatment of 4-CP in ultrapure water abruptly increased acute toxicity toward Daphnia magna while slightly decreased toxicity of 4-CP in effluent. In the presence of ZrO 2 catalyst, degradation of 4-CP as well as toxicity reduction was substantially improved mostly by adsorption of 4-CP onto the nanoparticles. It was found that benzoquinone, hydroquinone and 4-chlorocatechol were generated for ultrapure water sample while only 4-chlorocatechol was formed for effluent samples by gamma-ray treatment. As determined in this work, EC 50 values of benzoquinone (0.46 μM), hydroquinone (0.61 μM) and chlorocatechol (8.87 μM) were much lower than those of 4-CP (31.50 μM), explaining different toxicity changes of 4-CP in different matrices by gamma-ray treatment. The observed toxicity of gamma-ray treated 4-CP was well correlated with the one calculated from individual toxicity based on EC 50 value.

  9. 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)

  10. 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)

  11. Best Practices for NPDES Permit Writers and Pretreatment Coordinators to Address Toxic and Hazardous Chemical Discharges to POTWs

    EPA Pesticide Factsheets

    This guidance generally describes measures (“best practices”) NPDES permit writers and pretreatment coordinators should consider adopting to address hazardous and toxic chemical discharges to POTWs.

  12. Toxicity and utilization of chemical weapons: does toxicity and venom utilization contribute to the formation of species communities?

    PubMed Central

    Westermann, Fabian L; McPherson, Iain S; Jones, Tappey H; Milicich, Lesley; Lester, Philip J

    2015-01-01

    Toxicity and the utilization of venom are essential features in the ecology of many animal species and have been hypothesized to be important factors contributing to the assembly of communities through competitive interactions. Ants of the genus Monomorium utilize a variety of venom compositions, which have been reported to give them a competitive advantage. Here, we investigate two pairs of Monomorium species, which differ in the structural compositions of their venom and their co-occurrence patterns with the invasive Argentine ant. We looked at the effects of Monomorium venom toxicity, venom utilization, and aggressive physical interactions on Monomorium and Argentine ant survival rates during arena trials. The venom toxicity of the two species co-occurring with the invasive Argentine ants was found to be significantly higher than the toxicity of the two species which do not. There was no correlation between venom toxicity and Monomorium survival; however, three of the four Monomorium species displayed significant variability in their venom usage which was associated with the number of Argentine ant workers encountered during trials. Average Monomorium mortality varied significantly between species, and in Monomorium smithii and Monomorium antipodum, aggressive interactions with Argentine ants had a significant negative effect on their mortality. Our study demonstrates that different factors and strategies can contribute to the ability of a species to withstand the pressure of a dominant invader at high abundance, and venom chemistry appears to be only one of several strategies utilized. PMID:26357539

  13. Toxicity and utilization of chemical weapons: does toxicity and venom utilization contribute to the formation of species communities?

    PubMed

    Westermann, Fabian L; McPherson, Iain S; Jones, Tappey H; Milicich, Lesley; Lester, Philip J

    2015-08-01

    Toxicity and the utilization of venom are essential features in the ecology of many animal species and have been hypothesized to be important factors contributing to the assembly of communities through competitive interactions. Ants of the genus Monomorium utilize a variety of venom compositions, which have been reported to give them a competitive advantage. Here, we investigate two pairs of Monomorium species, which differ in the structural compositions of their venom and their co-occurrence patterns with the invasive Argentine ant. We looked at the effects of Monomorium venom toxicity, venom utilization, and aggressive physical interactions on Monomorium and Argentine ant survival rates during arena trials. The venom toxicity of the two species co-occurring with the invasive Argentine ants was found to be significantly higher than the toxicity of the two species which do not. There was no correlation between venom toxicity and Monomorium survival; however, three of the four Monomorium species displayed significant variability in their venom usage which was associated with the number of Argentine ant workers encountered during trials. Average Monomorium mortality varied significantly between species, and in Monomorium smithii and Monomorium antipodum, aggressive interactions with Argentine ants had a significant negative effect on their mortality. Our study demonstrates that different factors and strategies can contribute to the ability of a species to withstand the pressure of a dominant invader at high abundance, and venom chemistry appears to be only one of several strategies utilized.

  14. Effects of thermal food processing on the chemical structure and toxicity of fumonisin mycotoxins.

    PubMed

    Humpf, Hans-Ulrich; Voss, Kenneth A

    2004-09-01

    Fumonisins are Fusarium mycotoxins that occur in corn and corn-based foods. They are toxic to animals and at least one analogue, fumonisin B1, is carcinogenic to rodents. Their effect on human health is unclear, however, fumonisins are considered to be risk factors for cancer and possibly neural tube defects in some heavily exposed populations. It is therefore important to minimize exposures in these populations. Cleaning corn to remove damaged or moldy kernels reduces fumonisins in foods while milling increases their concentration in some and reduces their concentration in other products. Fumonisins are water-soluble and nixtamalization (cooking in alkaline water) lowers the fumonisin content of food products if the cooking liquid is discarded. Baking, frying, and extrusion cooking of corn at high temperatures ( > or = 190 degrees C) also reduces fumonisin concentrations in foods, with the amount of reduction achieved depending on cooking time, temperature, recipe, and other factors. However, the chemical fate of fumonisins in baked, fried, and extruded foods is not well understood and it is not known if the reduced concentrations result from thermal decomposition of fumonisins or from their binding to proteins, sugars or other compounds in food matrices. These possibilities might or might not be beneficial depending upon the bioavailability and inherent toxicity of decomposition products or the degree to which bound fumonisins are released in the gastrointestinal tract. In this review the affects of cooking and processing on the concentration and chemical structure of fumonisins as well as the toxicological consequences of known and likely fumonisin reaction products are discussed.

  15. The toxicity of oil and chemically dispersed oil to the seagrass Thalassia testudinum

    SciTech Connect

    Baca, B.J.; Getter, C.D.

    1982-10-01

    Turtle grass beds, a valuable natural resource, are diminishing throughout the tropics because of damage from dredging, boats, and other factors. The toxicity of chemical dispersants and crude oil to turtle grass was determined in the laboratory to assess the potential for damage from spills occurring in the field. Studies of water-soluble fractions (WSF) of crude oil in static bioassays showed that a chemical dispersant (Corexit 9527) increased the amount of total oil in water more than 50-fold. The toxicity of chemically dispersed oil was assessed by conventional (96-h 50% lethal concentration) methods in static systems, and the results were compared with toxicity measurements where the system was flushed after 12 h. Prudhoe Bay crude WSF was more toxic than dispersed oil or dispersant alone, possibly because of the large component of benzene, toluene, and C-2 benzene. The percentage of green (chlorophyllous) leaves was useful as evidence of toxicity. The importance of anatomical features such as recessed meristem and abundant leaf sheaths in protecting the growing region from waterborne pollutants was evident.

  16. Impact of Environmentally Based Chemical Hardness on Uranium Speciation and Toxicity in Six Aquatic Species

    PubMed Central

    Goulet, Richard R; Thompson, Patsy A; Serben, Kerrie C; Eickhoff, Curtis V

    2015-01-01

    Treated effluent discharge from uranium (U) mines and mills elevates the concentrations of U, calcium (Ca), magnesium (Mg), and sulfate (SO42–) above natural levels in receiving waters. Many investigations on the effect of hardness on U toxicity have been experiments on the combined effects of changes in hardness, pH, and alkalinity, which do not represent water chemistry downstream of U mines and mills. Therefore, more toxicity studies with water chemistry encountered downstream of U mines and mills are necessary to support predictive assessments of impacts of U discharge to the environment. Acute and chronic U toxicity laboratory bioassays were realized with 6 freshwater species in waters of low alkalinity, circumneutral pH, and a range of chemical hardness as found in field samples collected downstream of U mines and mills. In laboratory-tested waters, speciation calculations suggested that free uranyl ion concentrations remained constant despite increasing chemical hardness. When hardness increased while pH remained circumneutral and alkalinity low, U toxicity decreased only to Hyalella azteca and Pseudokirchneriella subcapitata. Also, Ca and Mg did not compete with U for the same uptake sites. The present study confirms that the majority of studies concluding that hardness affected U toxicity were in fact studies in which alkalinity and pH were the stronger influence. The results thus confirm that studies predicting impacts of U downstream of mines and mills should not consider chemical hardness. PMID:25475484

  17. Prediction of organ toxicity endpoints by QSAR modeling based on precise chemical-histopathology annotations.

    PubMed

    Myshkin, Eugene; Brennan, Richard; Khasanova, Tatiana; Sitnik, Tatiana; Serebriyskaya, Tatiana; Litvinova, Elena; Guryanov, Alexey; Nikolsky, Yuri; Nikolskaya, Tatiana; Bureeva, Svetlana

    2012-09-01

    The ability to accurately predict the toxicity of drug candidates from their chemical structure is critical for guiding experimental drug discovery toward safer medicines. Under the guidance of the MetaTox consortium (Thomson Reuters, CA, USA), which comprised toxicologists from the pharmaceutical industry and government agencies, we created a comprehensive ontology of toxic pathologies for 19 organs, classifying pathology terms by pathology type and functional organ substructure. By manual annotation of full-text research articles, the ontology was populated with chemical compounds causing specific histopathologies. Annotated compound-toxicity associations defined histologically from rat and mouse experiments were used to build quantitative structure-activity relationship models predicting subcategories of liver and kidney toxicity: liver necrosis, liver relative weight gain, liver lipid accumulation, nephron injury, kidney relative weight gain, and kidney necrosis. All models were validated using two independent test sets and demonstrated overall good performance: initial validation showed 0.80-0.96 sensitivity (correctly predicted toxic compounds) and 0.85-1.00 specificity (correctly predicted non-toxic compounds). Later validation against a test set of compounds newly added to the database in the 2 years following initial model generation showed 75-87% sensitivity and 60-78% specificity. General hepatotoxicity and nephrotoxicity models were less accurate, as expected for more complex endpoints. © 2012 John Wiley & Sons A/S.

  18. Hair as a monitor of toxic chemicals exposure

    SciTech Connect

    Jones, P.F.; Adams, S.; Baumgartner, W.A.

    1982-08-31

    The possibility of using hair analysis as a monitor of exposure to hydrazines and polychlorinated biphenyls (PCBs) was investigated. Two female Hartley guinea pigs injected with 0.6 milligrams (mg) of Aroclor-1254 had analyzable concentrations of the PCB in their hair. Analysis was made using glass capillary gas chromatography with an electron-capture detector. The levels ranged from 10 picograms/milligram (pg/mg) of Aroclor-1254 in washed hair to 100pg/mg in unwashed hair. Female Fischer-344 rats injected intraperitoneally with 60mg/kg unsymmetrical dimethyl hydrazine (UDMH), 10mg/kg monomethyl hydrazine (MMH) and/or 10mg/kg hydrazine did not have detectable amounts of these chemicals in their hair at 14, 30 or 42 days after injection. The hair samples did take up the hydrazines when suspended above solutions of the test compounds. The authors concluded that analyzing the PCB content of hair may be useful in providing a history of on-the-job PCB exposure.

  19. Use of submitochondrial particles for prediction of chemical toxicity in man

    SciTech Connect

    Knobeloch, L.M.; Blondin, G.A.; Harkin, J.M. )

    1990-05-01

    Three bioassays which use submitochondrial electron transport particles (ETP) to evaluate chemical toxicity have been developed. These tests were initially designed for use in water quality monitoring. However, they are also valuable for assessing the toxicity of new and existing chemicals. The current investigation studies the ability of these procedures to predict in vivo tissue concentrations associated with clinical illness in man. To examine this potential, data obtained using the mitochondrial tests were compared to chemical concentrations measured in human blood samples obtained during the acute stage of chemical-induced illness. Twenty-nine chemicals were used in the comparison including 6 metals, 8 pesticides, 5 drugs, 4 solvents and 3 alcohols. The results of this study support the hypothesis that the mitochondrial bioassays can successfully predict the in vivo toxicity of many diverse chemicals. Properly performed and evaluated, these short-term tests may be useful in identifying potential environmental pollutants, selecting compounds for market development and prioritizing substances for more extensive testing in animals.

  20. Software for analysis of chemical mixtures--composition, occurrence, distribution, and possible toxicity

    USGS Publications Warehouse

    Scott, Jonathon C.; Skach, Kenneth A.; Toccalino, Patricia L.

    2013-01-01

    The composition, occurrence, distribution, and possible toxicity of chemical mixtures in the environment are research concerns of the U.S. Geological Survey and others. The presence of specific chemical mixtures may serve as indicators of natural phenomena or human-caused events. Chemical mixtures may also have ecological, industrial, geochemical, or toxicological effects. Chemical-mixture occurrences vary by analyte composition and concentration. Four related computer programs have been developed by the National Water-Quality Assessment Program of the U.S. Geological Survey for research of chemical-mixture compositions, occurrences, distributions, and possible toxicities. The compositions and occurrences are identified for the user-supplied data, and therefore the resultant counts are constrained by the user’s choices for the selection of chemicals, reporting limits for the analytical methods, spatial coverage, and time span for the data supplied. The distribution of chemical mixtures may be spatial, temporal, and (or) related to some other variable, such as chemical usage. Possible toxicities optionally are estimated from user-supplied benchmark data. The software for the analysis of chemical mixtures described in this report is designed to work with chemical-analysis data files retrieved from the U.S. Geological Survey National Water Information System but can also be used with appropriately formatted data from other sources. Installation and usage of the mixture software are documented. This mixture software was designed to function with minimal changes on a variety of computer-operating systems. To obtain the software described herein and other U.S. Geological Survey software, visit http://water.usgs.gov/software/.

  1. In vitro toxicity assessment of a new series of high energy compounds.

    PubMed

    Hussain, S M; Frazier, J M

    2001-07-02

    Hydrazine is an aircraft fuel and propellant used by the US Air Force. Due to its toxicity the Propulsion Directorate of the Air Force Research Laboratory (AFRL/PR) has investigated alternative chemicals to replace hydrazine. AFRL/PR has synthesized a series of high energy chemicals (HECs), primarily hydrazine derivatives and amino containing compounds such as hydrazinium nitrate (HZN), 2-hydroxyethyl-hydrazine nitrate (HEHN), diethyl hydrazine nitrate (DEHN), ethanolamine nitrate (EAN), histamine dinitrate (HDN) and methoxylamine nitrate (MAN) to study as alternative chemical candidates. Although HECs are reliable constituents of powered propellant systems, they constitute an important class of toxic agents to which military and civilian personnel can be exposed. The current study was undertaken to examine the toxicity of HECs in primary hepatocytes in vitro. The effects of short-term exposure (4 h) of hepatocytes to HECs were investigated with reference to viability, mitochondrial function and oxidative stress markers. The results showed a decrease in mitochondrial activity, increase in lactate dehydrogenase (LDH) leakage and depletion of reduced glutathione (GSH) levels. The levels of reactive oxygen species (ROS) increased dose dependently in HZN, MAN and HDN exposed cells. However, there was no induction of ROS generation in EAN, DEHN and HEHN exposed cells. Depletion of GSH in hepatocytes by buthionine sulfoximine (BSO) prior to exposure to HZN increased its toxicity. The results suggest that at least one mechanism of HEC toxicity is mediated through oxidative stress.

  2. Chemical Compounds Toxic to Invertebrates Isolated from Marine Cyanobacteria of Potential Relevance to the Agricultural Industry

    PubMed Central

    Essack, Magbubah; Alzubaidy, Hanin S.; Bajic, Vladimir B.; Archer, John A. C.

    2014-01-01

    In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review. PMID:25356733

  3. Chemical compounds toxic to invertebrates isolated from marine cyanobacteria of potential relevance to the agricultural industry.

    PubMed

    Essack, Magbubah; Alzubaidy, Hanin S; Bajic, Vladimir B; Archer, John A C

    2014-10-29

    In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review.

  4. Toxic and teratogenic effects of chemical class fractions of a coal-gasification electrostatic precipitator tar.

    PubMed

    Schultz, T W; Dumont, J N; Buchanan, M V

    1983-12-01

    Dimethyl sulfoxide slurries of a coal gasifier electrostatic precipitator tar and its chemical class fractions were assayed for their toxicity and teratogenicity using early embryos of the frog Xenopus laevis. Of the 5 tar fractions the ether-soluble base and polyaromatic were found to be the most teratogenic and the ether-soluble acid and ether-soluble base were the most toxic. The teratogenic effects of the raw tar suggest synergism. The toxic effects to newly metamorphosed froglets is 1-2 orders of magnitude less than those observed for embryos. Chemical analysis shows dihydroxybenzenes and organonitrogen compounds to be the major components of the acid and base fractions, respectively. The neutral fractions contain mainly alkyl-substituted two-ring hydrocarbons.

  5. Comparison of toxicity of class-based organic chemicals to algae and fish based on discrimination of excess toxicity from baseline level.

    PubMed

    Li, Jin J; Tai, Hong W; Yu, Yang; Wen, Yang; Wang, Xiao H; Zhao, Yuan H

    2015-07-01

    Toxicity data to fish and algae were used to investigate excess toxicity between species. Results show that chemicals exhibiting excess toxicity to fish also show excess toxicity to algae for most of the compounds. This indicates that they share the same mode of action between species. Similar relationships between logKOW and toxicities to fish and algae for baseline and less inert compounds suggest that they have similar critical body residues in the two species. Differences in excess toxicity for some compounds suggest that there is a difference of physiological structure and metabolism between fish and algae. Some reactive compounds (e.g. polyamines) exhibit greater toxic effects for algae than those for fish because of relatively low bio-uptake potential of these hydrophilic compounds in fish as compared with that in algae. Esters exhibiting greater toxicity in fish than that in algae indicate that metabolism can affect the discrimination of excess toxicity from baseline level. Algae growth inhibition is a very good surrogate for fish lethality. This is not only because overall toxicity sensitivity to algae is greater than that to fish, but also the excess toxicity calculated from algal toxicity can better reflect reactivity of compounds with target molecules than fish toxicity.

  6. 40 CFR 372.85 - Toxic chemical release reporting form and instructions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS TOXIC CHEMICAL RELEASE... R Schedule 1 may be found on the following EPA Program Web site, http://www.epa.gov/tri. Any subsequent changes to the Form R or Form R Schedule 1 will be posted on this Web site. Submitters may...

  7. Acute Environmental Toxicity and Persistence of a Chemical Agent Simulant: 2-Chloroethyl Ethyl Sulfide (CEES)

    DTIC Science & Technology

    1988-11-01

    3 6 3.2.1 Vegetative Surfaces .................................... 37 3.2.2 Soil Surfaces...terrestrial and aquatic organisms based on contact toxicity and the chemical persistence of the simulant In soils and waters and on vegetative surfaces...processes. The volatility of CEES prevented any meaningful acquisition of particle size distributions. 14 2.2 EXPSRE P Four CEES exposure tests were

  8. Prioritizing ToxCast Chemicals Across Multiple Sectors of Toxicity Using ToxPi

    EPA Science Inventory

    The Toxicological Prioritization Index (ToxPi™) framework was developed as a decision-support tool to aid in the rational prioritization of chemicals for integrated toxicity testing. ToxPi consolidates information from multiple domains—including ToxCast™ in vitro bioactivity prof...

  9. Incorporating Biological, Chemical and Toxicological Knowledge into Predictive Models of Toxicity: Letter to the Editor

    EPA Science Inventory

    Thomas et al. (2012) recently published an evaluation of statistical models for classifying in vivo toxicity endpoints from ToxRefDB (Knudsen et al. 2009; Martin et al. 2009a and 2009b) using ToxCast in vitro bioactivity data (Judson et al. 2010) and chemical structure descriptor...

  10. SEDIMENT CHEMICAL CONTAMINATION AND TOXICITY ASSOCIATED WITH A COASTAL GOLF COURSE COMPLEX.

    EPA Science Inventory

    The increasing density of golf courses represents a potential source of sediment contamination to nearby coastal areas, the chemical and biological magnitude of which is almost unknown. The objective of this study was to determine the concentrations of contaminants and toxicities...

  11. 76 FR 7841 - Agency Information Collection Activities; Proposed Collections; Toxic Chemical Release Reporting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-11

    ... AGENCY Agency Information Collection Activities; Proposed Collections; Toxic Chemical Release Reporting... codes other than SIC codes 20 through 39): 212111, 212112, 212113 (correspond to SIC 12, Coal Mining (except 1241)); or 212221, 212222, 212231, 212234, 212299 (correspond to SIC 10, Metal Mining (except 1011...

  12. CHEMICAL CONTAMINATION AND TOXICITY ASSOCIATED WITH A COASTAL GOLF COURSE COMPLEX

    EPA Science Inventory

    The increasing density of golf courses represents a potential source of contamination to nearby coastal areas, the chemical and biological magnitude of which is almost unknown. The objective of this study was to compare the concentrations of contaminants and toxicities of sedime...

  13. MICHTOX: A MASS BALANCE AND BIOACCUMULATION MODEL FOR TOXIC CHEMICALS IN LAKE MICHIGAN

    EPA Science Inventory

    MICHTOX is a toxic chemical mass balance and bioaccumulation model for Lake Michigan. It was developed for USEPA's Region V in support of the Lake Michigan Lake-wide Management Plan (LaMP) to provide guidance on expected water quality improvements in response to critical pollutan...

  14. Novel approaches to improving the chemical safety of the meat chain towards toxicants.

    PubMed

    Engel, E; Ratel, J; Bouhlel, J; Planche, C; Meurillon, M

    2015-11-01

    In addition to microbiological issues, meat chemical safety is a growing concern for the public authorities, chain stakeholders and consumers. Meat may be contaminated by various chemical toxicants originating from the environment, treatments of agricultural production or food processing. Generally found at trace levels in meat, these toxicants may harm human health during chronic exposure. This paper overviews the key issues to be considered to ensure better control of their occurrence in meat and assessment of the related health risk. We first describe potential contaminants of meat products. Strategies to move towards a more efficient and systematic control of meat chemical safety are then presented in a second part, with a focus on emerging approaches based on toxicogenomics. The third part presents mitigation strategies to limit the impact of process-induced toxicants in meat. Finally, the last part introduces methodological advances to refine chemical risk assessment related to the occurrence of toxicants in meat by quantifying the influence of digestion on the fraction of food contaminants that may be assimilated by the human body. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. 40 CFR 372.85 - Toxic chemical release reporting form and instructions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS TOXIC CHEMICAL RELEASE... R Schedule 1 may be found on the following EPA Program Web site, http://www.epa.gov/tri. Any subsequent changes to the Form R or Form R Schedule 1 will be posted on this Web site. Submitters may also...

  16. Calculations of protective action distance for toxic chemical spills using nomographs

    SciTech Connect

    Lee, L.G.; Vail, J.A.; Gibeault, G.L.

    1995-04-01

    This document was produced for emergency use following a spill of liquid gas or finely divided solid (<100 micron) toxic chemicals. The information on the next few pages was kept deliberately terse and is limited to data and graphic aids needed for calculation of plume distance (protective action distance). All supporting material is provided as Appendices.

  17. U.S. EPA requires Cupertino cement company to report toxic chemicals, commit to environmental projects

    EPA Pesticide Factsheets

    SAN FRANCISCO - The U.S. Environmental Protection Agency announced a settlement with Lehigh Southwest Cement Company for failing to properly report releases of toxic chemicals at its Cupertino, Calif. plant. The company is required to pay a $47,600

  18. STRESS PATHWAY-BASED REPORTER ASSAYS TO ASSESS TOXICITY OF ENVIRONMENTAL CHEMICALS.

    EPA Science Inventory

    There is an increasing need for assays for the rapid and efficient assessment of toxicities of large numbers of environmental chemicals. To meet this need, we are developing cell-based reporter assays that measure the activation of key molecular stress pathways. We are using pro...

  19. Virtual Liver: integrating in vitro and in vivo data to predict chemical-induced toxicity

    EPA Science Inventory

    It is difficult to assess the health impact of long-term exposure to low levels of contaminants from animal studies. Current methods for testing the toxicity of a single chemical can cost millions of dollars, take up to two years and sacrifice thousands of animals. In vitro model...

  20. Virtual Liver: integrating in vitro and in vivo data to predict chemical-induced toxicity

    EPA Science Inventory

    It is difficult to assess the health impact of long-term exposure to low levels of contaminants from animal studies. Current methods for testing the toxicity of a single chemical can cost millions of dollars, take up to two years and sacrifice thousands of animals. In vitro model...

  1. SEDIMENT CHEMICAL CONTAMINATION AND TOXICITY ASSOCIATED WITH A COASTAL GOLF COURSE COMPLEX.

    EPA Science Inventory

    The increasing density of golf courses represents a potential source of sediment contamination to nearby coastal areas, the chemical and biological magnitude of which is almost unknown. The objective of this study was to determine the concentrations of contaminants and toxicities...

  2. Water quality objectives for mixtures of toxic chemicals: problems and perspectives.

    PubMed

    Vighi, M; Altenburger, R; Arrhenius, A; Backhaus, T; Bödeker, W; Blanck, H; Consolaro, F; Faust, M; Finizio, A; Froehner, K; Gramatica, P; Grimme, L H; Grönvall, F; Hamer, V; Scholze, M; Walter, H

    2003-02-01

    The need to develop water quality objectives not only for single substances but also for mixtures of chemicals seems evident. For that purpose, the conceptual basis could be the use of the two existing biometric models: concentration addition (CA) and independent action (IA), which is also called response addition. Both may allow calculation of the toxicity of mixtures of chemicals with similar modes of action (CA) or dissimilar modes of action (IA), respectively. The joint research project Prediction and Assessment of the Aquatic Toxicity of Mixtures of Chemicals (PREDICT) within the framework of the IVth Environment and Climate Programme of the European Commission, provided the opportunity to address (a) chemometric and QSAR criteria to classify substances as supposedly similarly or dissimilarly acting; (b) the predictive values of both models for the toxicity of mixtures at low, statistically nonsignificant effect concentrations of the individual components; and (c) the predictability of mixture toxicity at higher levels of biological complexity. In this article, the general outline, methodological approach, and some preliminary findings of PREDICT are presented. A procedure for classifying chemicals in relation to their structural and toxicological similarities has been developed. The predictive capabilities of CA and IA models have been demonstrated for single species and, to some extent, for multispecies testing. The role of very low effect concentrations in multiple mixtures has been evaluated. Problems and perspectives concerning the development of water quality objectives for mixtures are discussed.

  3. Prioritizing ToxCast Chemicals Across Multiple Sectors of Toxicity Using ToxPi

    EPA Science Inventory

    The Toxicological Prioritization Index (ToxPi™) framework was developed as a decision-support tool to aid in the rational prioritization of chemicals for integrated toxicity testing. ToxPi consolidates information from multiple domains—including ToxCast™ in vitro bioactivity prof...

  4. CHEMICAL CONTAMINATION AND TOXICITY ASSOCIATED WITH A COASTAL GOLF COURSE COMPLEX

    EPA Science Inventory

    The increasing density of golf courses represents a potential source of contamination to nearby coastal areas, the chemical and biological magnitude of which is almost unknown. The objective of this study was to compare the concentrations of contaminants and toxicities of sedime...

  5. MICHTOX: A MASS BALANCE AND BIOACCUMULATION MODEL FOR TOXIC CHEMICALS IN LAKE MICHIGAN

    EPA Science Inventory

    MICHTOX is a toxic chemical mass balance and bioaccumulation model for Lake Michigan. It was developed for USEPA's Region V in support of the Lake Michigan Lake-wide Management Plan (LaMP) to provide guidance on expected water quality improvements in response to critical pollutan...

  6. STRESS PATHWAY-BASED REPORTER ASSAYS TO ASSESS TOXICITY OF ENVIRONMENTAL CHEMICALS.

    EPA Science Inventory

    There is an increasing need for assays for the rapid and efficient assessment of toxicities of large numbers of environmental chemicals. To meet this need, we are developing cell-based reporter assays that measure the activation of key molecular stress pathways. We are using pro...

  7. Incorporating Biological, Chemical and Toxicological Knowledge into Predictive Models of Toxicity: Letter to the Editor

    EPA Science Inventory

    Thomas et al. (2012) recently published an evaluation of statistical models for classifying in vivo toxicity endpoints from ToxRefDB (Knudsen et al. 2009; Martin et al. 2009a and 2009b) using ToxCast in vitro bioactivity data (Judson et al. 2010) and chemical structure descriptor...

  8. 40 CFR 372.85 - Toxic chemical release reporting form and instructions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Toxic chemical release reporting form... of total releases in pounds (except for dioxin and dioxin-like compounds, which shall be reported in... dioxin-like compounds category. (A) For reports pertaining to a reporting year ending on or...

  9. Quinones and aromatic chemical compounds in particulate matter induce mitochondrial dysfunction: implications for ultrafine particle toxicity.

    PubMed

    Xia, Tian; Korge, Paavo; Weiss, James N; Li, Ning; Venkatesen, M Indira; Sioutas, Constantinos; Nel, Andre

    2004-10-01

    Particulate pollutants cause adverse health effects through the generation of oxidative stress. A key question is whether these effects are mediated by the particles or their chemical compounds. In this article we show that aliphatic, aromatic, and polar organic compounds, fractionated from diesel exhaust particles (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses showed that the quinone-enriched polar fraction was more potent than the polycyclic aromatic hydrocarbon (PAH)-enriched aromatic fraction in O2 .- generation, decrease of membrane potential (Delta-Psi m), loss of mitochondrial membrane mass, and induction of apoptosis. A major effect of the polar fraction was to promote cyclosporin A (CsA)-sensitive permeability transition pore (PTP) opening in isolated liver mitochondria. This opening effect is dependent on a direct effect on the PTP at low doses as well as on an effect on Delta-Psi m at high doses in calcium (Ca2+)-loaded mitochondria. The direct PTP effect was mimicked by redox-cycling DEP quinones. Although the aliphatic fraction failed to perturb mitochondrial function, the aromatic fraction increased the Ca2+ retention capacity at low doses and induced mitochondrial swelling and a decrease in Delta-Psi m at high doses. This swelling effect was mostly CsA insensitive and could be reproduced by a mixture of PAHs present in DEPs. These chemical effects on isolated mitochondria could be reproduced by intact DEPs as well as ambient ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles failed to exert mitochondrial effects. These results suggest that DEP and UFP effects on the PTP and Delta-Psi m are mediated by adsorbed chemicals rather than the particles themselves.

  10. Quinones and Aromatic Chemical Compounds in Particulate Matter Induce Mitochondrial Dysfunction: Implications for Ultrafine Particle Toxicity

    PubMed Central

    Xia, Tian; Korge, Paavo; Weiss, James N.; Li, Ning; Venkatesen, M. Indira; Sioutas, Constantinos; Nel, Andre

    2004-01-01

    Particulate pollutants cause adverse health effects through the generation of oxidative stress. A key question is whether these effects are mediated by the particles or their chemical compounds. In this article we show that aliphatic, aromatic, and polar organic compounds, fractionated from diesel exhaust particles (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses showed that the quinone-enriched polar fraction was more potent than the polycyclic aromatic hydrocarbon (PAH)–enriched aromatic fraction in O2•− generation, decrease of membrane potential (ΔΨm), loss of mitochondrial membrane mass, and induction of apoptosis. A major effect of the polar fraction was to promote cyclosporin A (CsA)–sensitive permeability transition pore (PTP) opening in isolated liver mitochondria. This opening effect is dependent on a direct effect on the PTP at low doses as well as on an effect on ΔΨm at high doses in calcium (Ca2+)-loaded mitochondria. The direct PTP effect was mimicked by redox-cycling DEP quinones. Although the aliphatic fraction failed to perturb mitochondrial function, the aromatic fraction increased the Ca2+ retention capacity at low doses and induced mitochondrial swelling and a decrease in ΔΨm at high doses. This swelling effect was mostly CsA insensitive and could be reproduced by a mixture of PAHs present in DEPs. These chemical effects on isolated mitochondria could be reproduced by intact DEPs as well as ambient ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles failed to exert mitochondrial effects. These results suggest that DEP and UFP effects on the PTP and ΔΨm are mediated by adsorbed chemicals rather than the particles themselves. PMID:15471724

  11. Framework for identifying chemicals with structural features associated with the potential to act as developmental or reproductive toxicants.

    PubMed

    Wu, Shengde; Fisher, Joan; Naciff, Jorge; Laufersweiler, Michael; Lester, Cathy; Daston, George; Blackburn, Karen

    2013-12-16

    Developmental and reproductive toxicity (DART) end points are important hazard end points that need to be addressed in the risk assessment of chemicals to determine whether or not they are the critical effects in the overall risk assessment. These hazard end points are difficult to predict using current in silico tools because of the diversity of mechanisms of action that elicit DART effects and the potential for narrow windows of vulnerability. DART end points have been projected to consume the majority of animals used for compliance with REACH; thus, additional nonanimal predictive tools are urgently needed. This article presents an empirically based decision tree for determining whether or not a chemical has receptor-binding properties and structural features that are consistent with chemical structures known to have toxicity for DART end points. The decision tree is based on a detailed review of 716 chemicals (664 positive, 16 negative, and 36 with insufficient data) that have DART end-point data and are grouped into defined receptor binding and chemical domains. When tested against a group of chemicals not included in the training set, the decision tree is shown to identify a high percentage of chemicals with known DART effects. It is proposed that this decision tree could be used both as a component of a screening system to identify chemicals of potential concern and as a component of weight-of-evidence decisions based on structure-activity relationships (SAR) to fill data gaps without generating additional test data. In addition, the chemical groupings generated could be used as a starting point for the development of hypotheses for in vitro testing to elucidate mode of action and ultimately in the development of refined SAR principles for DART that incorporate mode of action (adverse outcome pathways).

  12. Predicting aquatic toxicities of chemical pesticides in multiple test species using nonlinear QSTR modeling approaches.

    PubMed

    Basant, Nikita; Gupta, Shikha; Singh, Kunwar P

    2015-11-01

    In this study, we established nonlinear quantitative-structure toxicity relationship (QSTR) models for predicting the toxicities of chemical pesticides in multiple aquatic test species following the OECD (Organization for Economic Cooperation and Development) guidelines. The decision tree forest (DTF) and decision tree boost (DTB) based QSTR models were constructed using a pesticides toxicity dataset in Selenastrum capricornutum and a set of six descriptors. Other six toxicity data sets were used for external validation of the constructed QSTRs. Global QSTR models were also constructed using the combined dataset of all the seven species. The diversity in chemical structures and nonlinearity in the data were evaluated. Model validation was performed deriving several statistical coefficients for the test data and the prediction and generalization abilities of the QSTRs were evaluated. Both the QSTR models identified WPSA1 (weighted charged partial positive surface area) as the most influential descriptor. The DTF and DTB QSTRs performed relatively better than the single decision tree (SDT) and support vector machines (SVM) models used as a benchmark here and yielded R(2) of 0.886 and 0.964 between the measured and predicted toxicity values in the complete dataset (S. capricornutum). The QSTR models applied to six other aquatic species toxicity data yielded R(2) of >0.92 (DTF) and >0.97 (DTB), respectively. The prediction accuracies of the global models were comparable with those of the S. capricornutum models. The results suggest for the appropriateness of the developed QSTR models to reliably predict the aquatic toxicity of chemicals and can be used for regulatory purpose.

  13. Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms.

    PubMed

    Kleinstreuer, Nicole C; Yang, Jian; Berg, Ellen L; Knudsen, Thomas B; Richard, Ann M; Martin, Matthew T; Reif, David M; Judson, Richard S; Polokoff, Mark; Dix, David J; Kavlock, Robert J; Houck, Keith A

    2014-06-01

    Addressing the safety aspects of drugs and environmental chemicals has historically been undertaken through animal testing. However, the quantity of chemicals in need of assessment and the challenges of species extrapolation require the development of alternative approaches. Our approach, the US Environmental Protection Agency's ToxCast program, utilizes a large suite of in vitro and model organism assays to interrogate important chemical libraries and computationally analyze bioactivity profiles. Here we evaluated one component of the ToxCast program, the use of primary human cell systems, by screening for chemicals that disrupt physiologically important pathways. Chemical-response signatures for 87 endpoints covering molecular functions relevant to toxic and therapeutic pathways were generated in eight cell systems for 641 environmental chemicals and 135 reference pharmaceuticals and failed drugs. Computational clustering of the profiling data provided insights into the polypharmacology and potential off-target effects for many chemicals that have limited or no toxicity information. The endpoints measured can be closely linked to in vivo outcomes, such as the upregulation of tissue factor in endothelial cell systems by compounds linked to the risk of thrombosis in vivo. Our results demonstrate that assaying complex biological pathways in primary human cells can identify potential chemical targets, toxicological liabilities and mechanisms useful for elucidating adverse outcome pathways.

  14. 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.

  15. Oral LD50 toxicity modeling and prediction of per- and polyfluorinated chemicals on rat and mouse.

    PubMed

    Bhhatarai, Barun; Gramatica, Paola

    2011-05-01

    Quantitative structure-activity relationship (QSAR) analyses were performed using the LD(50) oral toxicity data of per- and polyfluorinated chemicals (PFCs) on rodents: rat and mouse. PFCs are studied under the EU project CADASTER which uses the available experimental data for prediction and prioritization of toxic chemicals for risk assessment by using the in silico tools. The methodology presented here applies chemometrical analysis on the existing experimental data and predicts the toxicity of new compounds. QSAR analyses were performed on the available 58 mouse and 50 rat LD(50) oral data using multiple linear regression (MLR) based on theoretical molecular descriptors selected by genetic algorithm (GA). Training and prediction sets were prepared a priori from available experimental datasets in terms of structure and response. These sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the models were verified on 376 per- and polyfluorinated chemicals including those in REACH preregistration list. The rat and mouse endpoints were predicted by each model for the studied compounds, and finally 30 compounds, all perfluorinated, were prioritized as most important for experimental toxicity analysis under the project. In addition, cumulative study on compounds within the AD of all four models, including two earlier published models on LC(50) rodent analysis was studied and the cumulative toxicity trend was observed using principal component analysis (PCA). The similarities and the differences observed in terms of descriptors and chemical/mechanistic meaning encoded by descriptors to prioritize the most toxic compounds are highlighted.

  16. A new index to assess chemicals increasing the greenhouse effect based on their toxicity to algae.

    PubMed

    Wang, Ting; Zhang, Xiaoxian; Tian, Dayong; Gao, Ya; Lin, Zhifen; Liu, Ying; Kong, Lingyun

    2015-11-01

    CO2, as the typical greenhouse gas causing the greenhouse effect, is a major global environmental problem and has attracted increasing attention from governments. Using algae to eliminate CO2, which has been proposed as an effective way to reduce the greenhouse effect in the past decades, can be disturbed by a growing number of artificial chemicals. Thus, seven types of chemicals and Selenastrum capricornutum (algae) were examined in this study, and the good consistency between the toxicity of artificial chemicals to algae and the disturbance of carbon fixation by the chemicals was revealed. This consistency showed that the disturbance of an increasing number of artificial chemicals to the carbon fixation of algae might be a "malware" worsening the global greenhouse effect. Therefore, this study proposes an original, promising index to assess the risk of deepening the greenhouse effect by artificial chemicals before they are produced and marketed. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. The underlying toxicological mechanism of chemical mixtures: a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum.

    PubMed

    Tian, Dayong; Lin, Zhifen; Zhou, Xianghong; Yin, Daqiang

    2013-10-15

    Intracellular chemical reaction of chemical mixtures is one of the main reasons that cause synergistic or antagonistic effects. However, it still remains unclear what the influencing factors on the intracellular chemical reaction are, and how they influence on the toxicological mechanism of chemical mixtures. To reveal this underlying toxicological mechanism of chemical mixtures, a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum was employed, and both their joint effects and mixture toxicity were observed. Then series of two-step linear regressions were performed to describe the relationships between joint effects, the expected additive toxicities and descriptors of individual chemicals (including concentrations, binding affinity to receptors, octanol/water partition coefficients). Based on the quantitative relationships, the underlying joint toxicological mechanisms were revealed. The result shows that, for mixtures with their joint effects resulting from intracellular chemical reaction, their underlying toxicological mechanism depends on not only their interaction with target proteins, but also their transmembrane actions and their concentrations. In addition, two generic points of toxicological mechanism were proposed including the influencing factors on intracellular chemical reaction and the difference of the toxicological mechanism between single reactive chemicals and their mixtures. This study provided an insight into the understanding of the underlying toxicological mechanism for chemical mixtures with intracellular chemical reaction.

  18. Multiple life stage sensitivity of a deposit-feeding polychaete to chemical toxicants in sediment

    SciTech Connect

    Rice, C.A.; Sibley, T.; Ylitalo, G.M.; Casillas, E.

    1995-12-31

    By focusing on acute toxicity in species with habitat and food preferences often quite different from the environments of primary interest; that is, the depositional, fine-grained, organically enriched benthos, standard methods of testing sediment toxicity using single species have important problems of relevance in terms of test endpoints and target species. This study addresses these issues by building a set of baseline toxicity data that emphasizes critical life stage sensitivity over a wide range of toxicant concentrations in long-term sediment exposures for an animal with a model life history. The opportunistic, deposit-feeding polychaete Armandia brevis was exposed to sediments supplemented with fluoranthene, cadmium, copper, lead, and mercury, alone and in a model mixture, for 60 days. Mortality and emergence from sediment were recorded daily, and growth and maturity were measured at 20, 40, and 60d. To measure recruitment, cultured larvae were presented with the same sediments and allowed to settle and complete metamorphosis. Differential endpoint sensitivity, and differential chemical toxicity were evaluated. In addition, sediment and tissue concentrations of organic toxicants were used to link toxic responses to body burdens, and to consider the role of benthic infauna as contaminant vectors in the marine environment.

  19. Atomic charges of individual reactive chemicals in binary mixtures determine their joint effects: an example of cyanogenic toxicants and aldehydes.

    PubMed

    Tian, Dayong; Lin, Zhifen; Yin, Daqiang; Zhang, Yalei; Kong, Deyang

    2012-02-01

    Environmental contaminants are usually encountered as mixtures, and many of these mixtures yield synergistic or antagonistic effects attributable to an intracellular chemical reaction that pose a potential threat on ecological systems. However, how atomic charges of individual chemicals determine their intracellular chemical reactions, and then determine the joint effects for mixtures containing reactive toxicants, is not well understood. To address this issue, the joint effects between cyanogenic toxicants and aldehydes on Photobacterium phosphoreum were observed in the present study. Their toxicological joint effects differed from one another. This difference is inherently related to the two atomic charges of the individual chemicals: the oxygen charge of -CHO (O(aldehyde toxicant)) in aldehyde toxicants and the carbon-atom charge of a carbon chain in the cyanogenic toxicant (C(cyanogenic toxicant)). Based on these two atomic charges, the following QSAR (quantitative structure-activity relationship) model was proposed: When (O(aldehyde toxicant) -C(cyanogenic toxicant) )> -0.125, the joint effect of equitoxic binary mixtures at median inhibition (TU, the sum of toxic units) can be calculated as TU = 1.00 ± 0.20; when (O(aldehyde toxicant) -C(cyanogenic toxicant) ) ≤ -0.125, the joint effect can be calculated using TU = - 27.6 x O (aldehyde toxicant) - 5.22 x C (cyanogenic toxicant) - 6.97 (n = 40, r = 0.887, SE = 0.195, F = 140, p < 0.001, q(2) (Loo) = 0.748; SE is the standard error of the regression, F is the F test statistic). The result provides insight into the relationship between the atomic charges and the joint effects for mixtures containing cyanogenic toxicants and aldehydes. This demonstrates that the essence of the joint effects resulting from intracellular chemical reactions depends on the atomic charges of individual chemicals. The present study provides a possible approach for the development of a QSAR model for mixtures containing reactive

  20. Chemical pollution and toxicity of water samples from stream receiving leachate from controlled municipal solid waste (MSW) landfill.

    PubMed

    Melnyk, A; Kuklińska, K; Wolska, L; Namieśnik, J

    2014-11-01

    The present study was aimed to determine the impact of municipal waste landfill on the pollution level of surface waters, and to investigate whether the choice and number of physical and chemical parameters monitored are sufficient for determining the actual risk related to bioavailability and mobility of contaminants. In 2007-2012, water samples were collected from the stream flowing through the site at two sampling locations, i.e. before the stream׳s entry to the landfill, and at the stream outlet from the landfill. The impact of leachate on the quality of stream water was observed in all samples. In 2007-2010, high values of TOC and conductivity in samples collected down the stream from the landfill were observed; the toxicity of these samples was much greater than that of samples collected up the stream from the landfill. In 2010-2012, a significant decrease of conductivity and TOC was observed, which may be related to the modernization of the landfill. Three tests were used to evaluate the toxicity of sampled water. As a novelty the application of Phytotoxkit F™ for determining water toxicity should be considered. Microtox(®) showed the lowest sensitivity of evaluating the toxicity of water samples, while Phytotoxkit F™ showed the highest. High mortality rates of Thamnocephalus platyurus in Thamnotoxkit F™ test can be caused by high conductivity, high concentration of TOC or the presence of compounds which are not accounted for in the water quality monitoring program. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Biological monitoring of occupational exposure to toxic chemicals. Collection, processing, and storage of specimens

    SciTech Connect

    Aitio, A.; Jaervisalo, J.

    1985-03-01

    Exposure to at least 100 different chemicals may be estimated on an individual basis from their concentrations in blood or urine. The present document reviews sources of error in the collection, processing and storage of specimens for this biological monitoring. Physiological factors cause variation in the concentration of chemicals in the body fluids. Distribution of water depends on posture. Exercise and meals cause changes in blood constituents. The urine output varies and, thus, the concentrations of dissolved chemicals change. Many toxic chemicals show short half times in the blood; thus, their concentrations depend on the timing of the specimen collection. Skin absorption may result in dramatically different chemical concentrations in different parts of the circulation. The stability of chemicals in the collected specimens is generally limited: chemical deterioration, adsorption, precipitation, and evaporation are the main causes of losses. For many chemicals, especially for trace elements, contamination of the specimen is the overwhelmingly most important source of error. As the range of the chemicals measured is wide, the relative importance of the sources of error is different for different chemicals. Information on most chemicals is at present very limited. Thus, before commencing a program on biological exposure monitoring, it is advisable to search the optimal conditions for specimen collection, processing, and storage.

  2. Examining predictors of chemical toxicity in freshwater fish using the random forest technique.

    PubMed

    Tuulaikhuu, Baigal-Amar; Guasch, Helena; García-Berthou, Emili

    2017-03-03

    Chemical pollution is one of the main issues globally threatening the enormous biodiversity of freshwater ecosystems. The toxicity of substances depends on many factors such as the chemical itself, the species affected, environmental conditions, exposure duration, and concentration. We used the random forest technique to examine the factors that mediate toxicity in a set of widespread fishes and analyses of covariance to further assess the importance of differential sensitivity among fish species. Among 13 variables, the 5 most important predictors of toxicity with random forests were, by order of importance, the chemical substance itself (i.e., Chemical Abstracts Service number considered as a categorical factor), octanol-water partition coefficient (log P), pollutant prioritization, ecological structure-activity relationship (ECOSAR) classification, and fish species for 50% lethal concentrations (LC50) and the chemical substance, fish species, log P, ECOSAR classification, and water temperature for no observed effect concentrations (NOECs). Fish species was a very important predictor for both endpoints and with the two contrasting statistical techniques used. Different fish species displayed very different relationships with log P, often with different slopes and with as much importance as the partition coefficient. Therefore, caution should be exercised when extrapolating toxicological results or relationships among species. In addition, further research is needed to determine species-specific sensitivities and unravel the mechanisms behind them.

  3. Toxic chemicals: can what we don't know harm us?

    PubMed

    deFur, P L; Foersom, L

    2000-02-01

    The Chesapeake Bay Program began more than 20 years ago with assessments of a number of key areas, relying on measurements of habitats, plant and animal populations, and physical and chemical conditions. This approach used wildlife as indicators of Bay "health" and of potential threats to human health. The extent of toxic chemical contamination was one of the assessment endpoints in the original survey. When the initial assessment was completed in 1983, the results of Bay-wide surveys indicated that several specific waterways were contaminated. These waters, the Elizabeth River, Virginia, the James River, Virginia, and Baltimore Harbor, Maryland, were targeted for specific actions to address the problems of historical and ongoing pollution. Over the past 10 years or more, data on some toxic chemical releases into and levels in the environment have been collected, but these data are limited in scope. Furthermore, these data are not used to assess threats to human health or more generally to nonhuman endpoints. New and existing data on environmental levels of chemicals and effects at low concentrations provide evidence that toxic chemicals may threaten both human and nonhuman health in the wider Bay system. Copyright 2000 Academic Press.

  4. Modeling and managing toxic chemicals: The Lake Michigan mass balance study

    SciTech Connect

    Endicott, D.D.; Richardson, W.L.

    1995-12-31

    The control and management of anthropogenic chemicals in the Great Lakes is an issue of great concern for 2 nations, 9 states and provinces, and 33 million people. As loadings from identified sources have been reduced, sometimes dramatic declines in toxic chemical concentrations have been observed to follow. However, human health and ecological effects from toxic chemicals remain topics of concern. There is also scientific debate regarding what factors control current toxic chemical concentrations in biotic and abiotic components of the Great lakes ecosystem. To address this latter issue, mathematical models are being developed to simulate the sources, transport, bioavailability, and bioaccumulation of four target chemicals (atrazine, mercury, PCBs, and trans-nonachlor). Preliminary modeling assessment by the authors suggested that PCB concentrations in Lake Michigan lake trout would remain greater than 1 mg/kg, even if all point and nonpoint sources in the watershed were eliminated. 2 factors control this result: (1) atmospheric sources are the largest PCB load component, and (2) the release of PCBs from the lake sediments by resuspension represents a huge internal mass flux. However, current data does not allow accurate estimation of either quantity. Because of the major ecological and economical consequences of decisions based upon the mass balance assessment, the modeling results require scientific confirmation.

  5. Detection of toxic industrial chemicals in water supplies using surface-enhanced Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Spencer, Kevin M.; Sylvia, James M.; Spencer, Sarah A.; Clauson, Susan L.

    2010-04-01

    An effective method to create fear in the populace is to endanger the water supply. Homeland Security places significant importance on ensuring drinking water integrity. Beyond terrorism, accidental supply contamination from a spill or chemical residual increases is a concern. A prominent class of toxic industrial chemicals (TICs) is pesticides, which are prevalent in agricultural use and can be very toxic in minute concentrations. Detection of TICs or warfare agents must be aggressive; the contaminant needs to be rapidly detected and identified to enable isolation and remediation of the contaminated water while continuing a clean water supply for the population. Awaiting laboratory analysis is unacceptable as delay in identification and remediation increases the likelihood of infection. Therefore, a portable or online water quality sensor is required that can produce rapid results. In this presentation, Surface-Enhanced Raman Spectroscopy (SERS) is discussed as a viable fieldable sensor that can be immersed directly into the water supply and can provide results in <5 minutes from the time the instrument is turned on until analysis is complete. The ability of SERS to detect several chemical warfare agent degradation products, simulants and toxic industrial chemicals in distilled water, tap water and untreated water will be shown. In addition, results for chemical warfare agent degradation products and simulants will be presented. Receiver operator characteristic (ROC) curves will also be presented.

  6. Toxic chemicals: Can what we don't know harm us?

    SciTech Connect

    Fur, P.L. de; Foersom, L.

    2000-02-01

    The Chesapeake Bay Program began more than 20 years ago with assessments of a number of key areas, relying on measurements of habitats, plant and animal populations, and physical and chemical conditions. This approach used wildlife as indicators of Bay health and of potential threats to human health. The extent of toxic chemical contamination was one of the assessment endpoints in the original survey. When the initial assessment was completed in 1983, the results of Bay-wide surveys indicated that several specific waterways were contaminated. These waters, the Elizabeth River, Virginia, the James River, Virginia, and Baltimore Harbor, Maryland, were targeted for specific actions to address the problems of historical and ongoing pollution. Over the past 10 years or more, data on some toxic chemical releases into and levels in the environment have been collected, but these data are limited in scope. Furthermore, these data are not used to assess threats to human health or more generally to nonhuman endpoints. New and existing data on environmental levels of chemicals and effects at low concentrations provide evidence that toxic chemicals may threaten both human and nonhuman health in the wider Bay system.

  7. Treating chronic arsenic toxicity with high selenium lentil diets

    SciTech Connect

    Sah, Shweta; Vandenberg, Albert; Smits, Judit

    2013-10-01

    Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we compare diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0 ppm As) or As (40 ppm As) water while consuming SK lentils (0.3 ppm Se) or northwestern USA lentils (< 0.01 ppm Se) diets for 14 weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14 weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans. - Highlights: • We reduce chronic arsenic toxicity in rats with a whole food solution. • High selenium lentils decrease liver damage and increase blood glutathione levels. • High selenium lentil diets increase urinary and fecal arsenic excretion. • High selenium lentil diets decrease arsenic levels in kidney, the storage organ. • High selenium lentil diets reverse arsenic suppression of the B cell

  8. Cutaneous signs of systemic toxicity due to dioxins and related chemicals

    SciTech Connect

    Dunagin, W.G.

    1984-04-01

    The controversy about dioxin effects on human health received a great deal of attention recently when the State of Missouri was declared to have a dioxin crisis. However, dioxin and several related chemicals are widespread throughout the world. Cutaneous signs play an important part in evaluating toxicity of dioxin and similar chemicals. Chloracne is the most sensitive indicator of significant dioxin exposure. Porphyria cutanea tarda and hyperpigmentation are other known cutaneous effects, and malignant fibrous histiocytomas of the skin may possibly be associated, although data are inconclusive on this point. The AMC Council on Scientific Affairs recommended that all physicians become familiar with chloracne and other toxic effects of dioxin. Dermatologists, especially, should be aware of the problem and may discover early cases of previously unsuspected exposure to this group of chemicals.

  9. Computer prediction of possible toxic action from chemical structure; the DEREK system.

    PubMed

    Sanderson, D M; Earnshaw, C G

    1991-07-01

    1. The development of DEREK, a computer-based expert system (derived from the LHASA chemical synthesis design program) for the qualitative prediction of possible toxic action of compounds on the basis of their chemical structure is described. 2. The system is able to perceive chemical sub-structures within molecules and relate these to a rulebase linking the sub-structures with likely types of toxicity. 3. Structures can be drawn in directly at a computer graphics terminal or retrieved automatically from a suitable in-house database. 4. The system is intended to aid the selection of compounds based on toxicological considerations, or separately to indicate specific toxicological properties to be tested for early in the evaluation of a compound, so saving time, money and some laboratory animals and resources.

  10. Genetics and susceptibility to toxic chemicals: do you (or should you) know your genetic profile?

    PubMed

    Lash, Lawrence H; Hines, Ronald N; Gonzalez, Frank J; Zacharewski, Timothy R; Rothstein, Mark A

    2003-05-01

    This review is based on a symposium/roundtable session, sponsored by the Division of Toxicology of the American Society for Pharmacology and Experimental Therapeutics, that was held at the 2002 Experimental Biology meeting in New Orleans, LA. The focus is on the role of pharmacogenomics in determining individual susceptibility to chemically induced toxicity. An individual's risk of disease from exposure to toxic chemicals is determined by a complex interplay between genetics, physiology, and concurrent or prior exposures to drugs and other chemicals. The first section of the review defines the basics of pharmacogenetics and pharmacogenomics and assesses the current state of the science. Selected applications to specific enzyme systems are summarized by way of example. New, state-of-the-art approaches to studying genetic determinants of susceptibility, including analytical methods and transgenic technology, are then discussed. Finally, ethical and legal concerns with the application of this knowledge and methodology to human health will be discussed.

  11. A comparison of the toxicity of 30 reference chemicals to Daphnia magna and Daphnia pulex

    SciTech Connect

    Lilius, H.; Haestbacka, T.; Isomaa, B.

    1995-12-01

    To determine whether significant differences exist in the sensitivity of different Daphnia species to toxicants, the acute toxicity of the first 30 MEIC (multicenter evaluation of in vitro cytotoxicity) reference chemicals was determined in two species of Daphnia: D. magna and D. pulex. Correlation and regression analysis of the EC50 data for immobilization showed a very good concordance (r = 0.97, slope = 1.02). A comparison between the EC50 data obtained for D. magna by two laboratories independently for the 50 MEIC chemicals also showed a good concordance (r = 0.93, slope = 0.91). In both comparisons the regression line did not differ significantly from the regression line for a 1:1 regression. The authors conclude that their study, including a set of reference chemicals, indicates that is no difference in the overall sensitivity of the two Daphnia species and the two clones of D. magna.

  12. Identification of compounds in heavy fuel oil that are chronically toxic to rainbow trout embryos by effects-driven chemical fractionation.

    PubMed

    Adams, Julie; Bornstein, Jason M; Munno, Keenan; Hollebone, Bruce; King, Thomas; Brown, R Stephen; Hodson, Peter V

    2014-04-01

    The present study isolated and identified compounds in heavy fuel oil 7102 (HFO 7102) that are bioavailable and chronically toxic to rainbow trout embryos (Oncorhynchus mykiss). An effects-driven chemical fractionation combined the chemical separation of oil with toxicity testing and chemical analyses of each fraction to identify the major classes of compounds associated with embryo toxicity. Toxicity was assessed with 2 exposure methods, a high-energy chemical dispersion of oil in water, which included oil droplets in test solutions, and water accommodated fractions which were produced by oiled gravel desorption columns, and which did not contain visible oil droplets. Fractions of HFO with high concentrations of naphthalenes, alkanes, asphaltenes, and resins were nontoxic to embryos over the range of concentrations tested. In contrast, fractions enriched with 3- to 4-ringed alkyl polycyclic aromatic hydrocarbons (PAHs) were embryotoxic, consistent with published studies of crude oils and individual alkyl PAHs. The rank order of fraction toxicity did not vary between the exposure methods and was consistent with their PAH content; fractions with higher-molecular weight alkyl PAHs were the most toxic. Exposure of juvenile trout to most fractions of HFO induced higher activities of cytochrome P450 enzymes, with a rank order of potency that varied with exposure method and differed somewhat from that of embryotoxicity. Induction reflected the bioavailability of PAHs but did not accurately predict embryotoxicity. © 2013 SETAC.

  13. Predicting changes in aquatic toxicity of chemicals resulting from solvent or dispersant use as vehicle.

    PubMed

    Kikuchi, Mikio; Nakagawa, Masamitsu; Tone, Suguru; Saito, Hotaka; Niino, Tatsuhiro; Nagasawa, Natsumi; Sawai, Jun

    2016-07-01

    The influence of two vehicles (N,N-dimethylformamide [DMF] as solvent and polyoxyethylene hydrogenated castor oil [HCO-40] as a dispersant) on the acute toxicity of eight hydrophobic chemicals with a non-specific mode of action to Daphnia magna was investigated according to the OECD Guidelines for the Testing of Chemicals, No. 202. An increased 48-h EC50 value for D. magna or reduced toxicity resulting from the addition of HCO-40 to the test medium was observed for five of the eight chemicals examined. Each of eight chemicals was dissolved in water at a concentration of either 10 mg/L or 1.0 mg/L, with or without DMF or HCO-40. Silicone film as a model of a biological membrane was then immersed in each solution, and the concentration of each chemical in the water was monitored until equilibrium was reached for each test substance, after which the adsorbed amount of each chemical was determined. The amounts of p-pentylphenol and four other substances with log Pow (1-octanol/water partition coefficient) values greater than 3.4 adsorbed onto the silicone film decreased with increasing concentrations of HCO-40. However, 3-chloro-4-fluoronitrobenzene and two other substances with log Pow values less than 2.6 demonstrated no changes in adsorption with either increasing HCO-40 concentration or the addition of DMF. The reduced adsorption in the presence of a vehicle on the silicone film correlated closely with changes in toxicity. These results indicate that the methodology developed in this study enables the prediction of changes in toxicity resulting from the addition of vehicles to a test system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Development of a fiber optic chemical sensor for detection of toxic vapors

    NASA Astrophysics Data System (ADS)

    Bansal, Lalitkumar

    Nerve agents are among the most potent of the chemical warfare agents being highly toxic in both liquid and gaseous form. In this thesis the development of a fiber optic chemical sensor for detection of organophosphorous nerve agent sarin precursor dimethyl-methylphosphonate (DMMP) is presented. The optical fiber sensor developed is based on the modified cladding approach using conducting polymer polypyrrole as a chemo-chromic material. Polypyrrole is synthesized by chemical oxidation and characterized by FTIR and Raman Spectroscopy. To characterize the electrical and optical property changes that come about in polypyrrole upon exposure to DMMP, four probe technique, ellipsometry, thin film transmission are used. The polypyrrole coating is applied to un-cladded fiber core using two different coating techniques, i.e. in-situ deposition and monomer vapor phase deposition. Preliminary results show an intensity decrease of 2.1% when the sensing element is exposed to 134ppm of DMMP. Three different dopant anions, i.e. 1--5, Napthalene disulphonic acid, Anthraquenone sulphonic acid and Hydrochloric acid, are added to improve the sensor sensitivity. The developed device is tested for DMMP sensitivity optimizations in terms of substrate nature, Cu2+ dopant, waveguide geometry, and light source intensity. The sensitivity optimization has resulted in a 25.75% sensor response and a detection of 26ppm of DMMP concentration. Selectivity and environmental stability of the developed device is investigated. The mechanical property and adhesion investigated using the nanoindentation and ASTM D-4541 pull-off test method. The influence of these adhesion enhancements on the sensor response is investigated.

  15. Sublethal copper toxicity impairs chemical orientation in the crayfish, Orconectes rusticus.

    PubMed

    Lahman, Sara E; Trent, Kaitlyn R; Moore, Paul A

    2015-03-01

    Before reaching concentrations that are high enough to cause mortality, elevated levels of chemical pollution can significantly alter a keystone indicator species' ability to extract sensory information. To organisms that rely on chemical signals to make crucial ecological decisions, increased amounts of a pollutant may impact chemoreceptive abilities by altering the perception of the sensory landscape or impairing the functioning of sensory organs. Heavy metal pollutants entering an aquatic ecosystem are of increasing concern due to discernible effects on chemoreception in many ecologically and economically important species. In order to determine the effects of sublethal copper toxicity on chemically mediated behavior, male and female rusty crayfish, Orconectes rusticus, were exposed to ecologically relevant concentrations of copper (4.5, 45, and 450 µg/l) for 120 h. Following exposure, crayfish were allowed to orient toward a food odor stimulus. During orientation trials, select crayfish oriented under a point or nonpoint source copper background pollutant at the same concentration as the exposure period. Orientation trials were videotaped and analyzed using EthoVision XT 8.5 (Noldus Information Technology, The Netherlands) for differences in overall success in locating the food source and orienting parameters. Significant differences were found in the overall orientation ability of O. rusticus to locate an odor source when previously exposed to copper in combination with a source of pollution in the background of orientation trials. Crayfish exposed to copper in any capacity during the experiment (regardless of concentration or background during trials) showed slower walking speeds toward the source, decreased turning angles, increased heading angles toward the source, and decreased upstream heading angles. Results from this experiment support that copper impairs the ability of crayfish to detect, process, and/or respond appropriately to chemosensory

  16. The chemical toxicity of cesium in Indian mustard (Brassica juncea L.) seedlings.

    PubMed

    Lai, Jin-Long; Tao, Zong-Ya; Fu, Qian; Han, Na; Wu, Guo; Zhang, Hong; Lu, Hong; Luo, Xue-Gang

    2016-08-01

    To distinguish between the radiological and chemical effects of radiocesium, we study the chemical toxicity of cesium in the seedlings of Indian mustard (Brassica juncea L.). In this study, the experiment was designed in two factors and five levels random block design to investigate the interaction effects of Cs and K. Results showed that excessive Cs was one of the main factors influence the growth of Brassica juncea seedlings. And the toxicity of Cs in Brassica juncea is likely to be caused by Cs interacts with K-binding sites in essential K-dependent protein, either competes with K for essential biochemical functions, causing intracellular metabolic disturbance. To test the hypothesis that the toxicity of Cs might cause intracellular metabolic disturbance, next-generation sequencing (NGS)-based Illumina paired-end Solexa sequencing platform was employed to analysis the changes in gene expression, and understand the key genes in B. juncea seedlings responding to the toxicity of Cs. Based on the assembled de novo transcriptome, 2032 DEGs that play significant roles in the response to the toxicity of Cs were identified. Further analysis showed that excessive Cs is disturbance the auxin signal transduction pathway, and inhibited the indoleacetic acid-induced protein (AUX/IAA) genes expression eventually lead the seedlings growth and development be inhibited. The results suggest that disturbances to tryptophan metabolism might be linked to changes in growth.

  17. Use of biosensors to screen urine samples for potentially toxic chemicals.

    PubMed

    Horswell, Jacqui; Dickson, Stuart

    2003-09-01

    Forensic toxicology laboratories are often required to implicate or exclude poisoning as a factor in a death or unexplained illness. An analytical tool which enables toxicologists to screen a wide variety of common poisons would be extremely useful. In this paper, we describe the use of a bacterial biosensor for detecting the presence of commonly encountered potentially toxic chemicals in urine. The biosensor responds to any chemical that causes metabolic stress to the bacterial cell and the response is in direct proportion to the concentration of the stressor. This allows a measure of the concentration of a toxicant in urine, without knowing exactly what the toxic compound(s) may be. This affords a distinct advantage over conventional analytical techniques, which require an extensive screening program before it is even known that a toxic compound is present. This preliminary investigation has shown that this biosensor can indicate the presence, in urine, of herbicides such as glyphosate, 2,4-dichlorophenoxyacetic acid, and 2,4,5-trichlorophenoxyacetic acid; the biocide pentachlorophenol; or inorganic poisons such as arsenic, mercury, and cyanide. The biosensor was also shown to be sensitive to a concentration range of these toxicants likely to be found in samples submitted for toxicological analysis.

  18. Acclimation of Chlamydomonas reinhardtii to ultraviolet radiation and its impact on chemical toxicity.

    PubMed

    Korkaric, Muris; Xiao, Mao; Behra, Renata; Eggen, Rik I L

    2015-10-01

    The toxicity of chemical pollutants can be modulated under stressful environmental conditions, such as increased temperature, salinity or ultraviolet radiation (UVR), due to the interaction of effects during simultaneous stressor exposure. However, organisms may acclimate to such conditions by activation of physiological and biochemical defence mechanisms. In sequential exposures, organisms acclimated to environmental stressors may display an increased sensitivity or co-tolerance towards chemical pollutants. It has been suggested that co-tolerance might be expected for similarly acting stressors due to common defence mechanisms. To test this for combinations of UVR and chemical stressors, we first acclimatized the model green alga Chlamydomonas reinhardtii to UVR and subsequently compared the sensitivity of UVR pre-exposed and control algae towards chemicals. Selected chemicals all act on photosynthesis and thus share a common physiological target, but display distinct toxicity mechanisms. Results showed that UVR pre-exposure for four days partially inhibited algal growth and photosynthesis, but also increased algal tolerance to higher UVR levels, confirming UVR acclimation. HPLC analysis of algal pigments indicated that UVR acclimation might in part be explained by the protective function of lutein while the contribution of UVR absorbing compounds was less clear. Challenge exposure to chemicals in the absence of UVR showed that acclimated algae were co-tolerant to the photosensitizer rose bengal, but not to the herbicides paraquat and diuron, suggesting that the fast physiological and biochemical defence mechanisms that conferred tolerance of algae towards higher UVR levels were related to singlet oxygen defence. The presented study suggests that knowledge of the molecular toxicity mechanisms of chemicals, rather than their general physiological target, is needed in order to predict co-tolerance between environmental and chemical stressors.

  19. The complex interaction between marine debris and toxic chemicals in the ocean.

    PubMed

    Engler, Richard E

    2012-11-20

    Marine debris, especially plastic debris, is widely recognized as a global environmental problem. There has been substantial research on the impacts of plastic marine debris, such as entanglement and ingestion. These impacts are largely due to the physical presence of plastic debris. In recent years there has been an increasing focus on the impacts of toxic chemicals as they relate to plastic debris. Some plastic debris acts as a source of toxic chemicals: substances that were added to the plastic during manufacturing leach from plastic debris. Plastic debris also acts as a sink for toxic chemicals. Plastic sorbs persistent, bioaccumulative, and toxic substances (PBTs), such as polychlorinated biphenyls (PCBs) and dioxins, from the water or sediment. These PBTs may desorb when the plastic is ingested by any of a variety of marine species. This broad look at the current research suggests that while there is significant uncertainty and complexity in the kinetics and thermodynamics of the interaction, plastic debris appears to act as a vector transferring PBTs from the water to the food web, increasing risk throughout the marine food web, including humans. Because of the extremely long lifetime of plastic and PBTs in the ocean, prevention strategies are vital to minimizing these risks.

  20. Toxic effects of chemical dispersant Corexit 9500 on water flea Daphnia magna.

    PubMed

    Toyota, Kenji; McNabb, Nicole A; Spyropoulos, Demetri D; Iguchi, Taisen; Kohno, Satomi

    2017-02-01

    In 2010, approximately 2.1 million gallons of chemical dispersants, mainly Corexit 9500, were applied in the Gulf of Mexico to prevent the oil slick from reaching shorelines and to accelerate biodegradation of oil during the Deepwater Horizon oil spill. Recent studies have revealed toxic effects of Corexit 9500 on marine microzooplankton that play important roles in food chains in marine ecosystems. However, there is still little known about the toxic effects of Corexit 9500 on freshwater zooplankton, even though oil spills do occur in freshwater and chemical dispersants may be used in response to these spills. The cladoceran crustacean, water flea Daphnia magna, is a well-established model species for various toxicological tests, including detection of juvenile hormone-like activity in test compounds. In this study, we conducted laboratory experiments to investigate the acute and chronic toxicity of Corexit 9500 using D. magna. The acute toxicity test was conducted according to OECD TG202 and the 48 h EC50 was 1.31 ppm (CIs 0.99-1.64 ppm). The reproductive chronic toxicity test was performed following OECD TG211 ANNEX 7 and 21 days LOEC and NOEC values were 4.0 and 2.0 ppm, respectively. These results indicate that Corexit 9500 has toxic effects on daphnids, particularly during the neonatal developmental stage, which is consistent with marine zooplankton results, whereas juvenile hormone-like activity was not identified. Therefore, our findings of the adverse effects of Corexit 9500 on daphnids suggest that application of this type of chemical dispersant may have catastrophic impacts on freshwater ecosystems by disrupting the key food chain network. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Assessing contaminant sensitivity of endangered and threatened aquatic species: Part I. Acute toxicity of five chemicals

    USGS Publications Warehouse

    Dwyer, F.J.; Mayer, F.L.; Sappington, L.C.; Buckler, D.R.; Bridges, C.M.; Greer, I.E.; Hardesty, D.K.; Henke, C.E.; Ingersoll, C.G.; Kunz, J.L.; Whites, D.W.; Augspurger, T.; Mount, D.R.; Hattala, K.; Neuderfer, G.N.

    2005-01-01

    Assessment of contaminant impacts to federally identified endangered, threatened and candidate, and state-identified endangered species (collectively referred to as "listed" species) requires understanding of a species' sensitivities to particular chemicals. The most direct approach would be to determine the sensitivity of a listed species to a particular contaminant or perturbation. An indirect approach for aquatic species would be application of toxicity data obtained from standard test procedures and species commonly used in laboratory toxicity tests. Common test species (fathead minnow, Pimephales promelas; sheepshead minnow, Cyprinodon variegatus; and rainbow trout, Oncorhynchus mykiss) and 17 listed or closely related species were tested in acute 96-hour water exposures with five chemicals (carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin) representing a broad range of toxic modes of action. No single species was the most sensitive to all chemicals. For the three standard test species evaluated, the rainbow trout was more sensitive than either the fathead minnow or sheepshead minnow and was equal to or more sensitive than listed and related species 81% of the time. To estimate an LC50 for a listed species, a factor of 0.63 can be applied to the geometric mean LC50 of rainbow trout toxicity data, and more conservative factors can be determined using variance estimates (0.46 based on 1 SD of the mean and 0.33 based on 2 SD of the mean). Additionally, a low- or no-acute effect concentration can be estimated by multiplying the respective LC50 by a factor of approximately 0.56, which supports the United States Environmental Protection Agency approach of multiplying the final acute value by 0.5 (division by 2). When captive or locally abundant populations of listed fish are available, consideration should be given to direct testing. When direct toxicity testing cannot be performed, approaches for developing protective measures using common test

  2. Chemically Diverse Toxicants Converge on Fyn and c-Cbl to Disrupt Precursor Cell Function

    PubMed Central

    Li, Zaibo; Dong, Tiefei; Pröschel, Chris; Noble, Mark

    2007-01-01

    Identification of common mechanistic principles that shed light on the action of the many chemically diverse toxicants to which we are exposed is of central importance in understanding how toxicants disrupt normal cellular function and in developing more effective means of protecting against such effects. Of particular importance is identifying mechanisms operative at environmentally relevant toxicant exposure levels. Chemically diverse toxicants exhibit striking convergence, at environmentally relevant exposure levels, on pathway-specific disruption of receptor tyrosine kinase (RTK) signaling required for cell division in central nervous system (CNS) progenitor cells. Relatively small toxicant-induced increases in oxidative status are associated with Fyn kinase activation, leading to secondary activation of the c-Cbl ubiquitin ligase. Fyn/c-Cbl pathway activation by these pro-oxidative changes causes specific reductions, in vitro and in vivo, in levels of the c-Cbl target platelet-derived growth factor receptor-α and other c-Cbl targets, but not of the TrkC RTK (which is not a c-Cbl target). Sequential Fyn and c-Cbl activation, with consequent pathway-specific suppression of RTK signaling, is induced by levels of methylmercury and lead that affect large segments of the population, as well as by paraquat, an organic herbicide. Our results identify a novel regulatory pathway of oxidant-mediated Fyn/c-Cbl activation as a shared mechanism of action of chemically diverse toxicants at environmentally relevant levels, and as a means by which increased oxidative status may disrupt mitogenic signaling. These results provide one of a small number of general mechanistic principles in toxicology, and the only such principle integrating toxicology, precursor cell biology, redox biology, and signaling pathway analysis in a predictive framework of broad potential relevance to the understanding of pro-oxidant–mediated disruption of normal development. PMID:17298174

  3. Assessing contaminant sensitivity of endangered and threatened aquatic species: part I. Acute toxicity of five chemicals.

    PubMed

    Dwyer, F J; Mayer, F L; Sappington, L C; Buckler, D R; Bridges, C M; Greer, I E; Hardesty, D K; Henke, C E; Ingersoll, C G; Kunz, J L; Whites, D W; Augspurger, T; Mount, D R; Hattala, K; Neuderfer, G N

    2005-02-01

    Assessment of contaminant impacts to federally identified endangered, threatened and candidate, and state-identified endangered species (collectively referred to as "listed" species) requires understanding of a species' sensitivities to particular chemicals. The most direct approach would be to determine the sensitivity of a listed species to a particular contaminant or perturbation. An indirect approach for aquatic species would be application of toxicity data obtained from standard test procedures and species commonly used in laboratory toxicity tests. Common test species (fathead minnow, Pimephales promelas; sheepshead minnow, Cyprinodon variegatus; and rainbow trout, Oncorhynchus mykiss) and 17 listed or closely related species were tested in acute 96-hour water exposures with five chemicals (carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin) representing a broad range of toxic modes of action. No single species was the most sensitive to all chemicals. For the three standard test species evaluated, the rainbow trout was more sensitive than either the fathead minnow or sheepshead minnow and was equal to or more sensitive than listed and related species 81% of the time. To estimate an LC50 for a listed species, a factor of 0.63 can be applied to the geometric mean LC50 of rainbow trout toxicity data, and more conservative factors can be determined using variance estimates (0.46 based on 1 SD of the mean and 0.33 based on 2 SD of the mean). Additionally, a low- or no-acute effect concentration can be estimated by multiplying the respective LC50 by a factor of approximately 0.56, which supports the United States Environmental Protection Agency approach of multiplying the final acute value by 0.5 (division by 2). When captive or locally abundant populations of listed fish are available, consideration should be given to direct testing. When direct toxicity testing cannot be performed, approaches for developing protective measures using common test

  4. EPAS TOXCAST PROGRAM FOR PREDICTING HAZARD AND PRIORITIZING TOXICITY TESTING OF ENVIRONMENTAL CHEMICALS(S).

    EPA Science Inventory

    EPAs National Center for Computational Toxicology is developing methods that apply computational chemistry, high-throughput screening (HTS) and genomic technologies to predict potential toxicity and prioritize the use of limited testing resources.

  5. Nonclinical reproductive toxicity testing requirements for drugs, pesticides, and industrial chemicals in India and China.

    PubMed

    Rao, K S; Dong, Jing

    2013-01-01

    India and China have booming chemical, agrochemical, and pharmaceutical industries. Both countries also represent expanding markets for foreign chemical and healthcare companies. All such products require reproductive toxicity testing before marketing. The ICH testing guidelines for medicinal products are not applicable in China and India. Nonetheless, reproductive toxicity studies designed and run to ICH principles are generally acceptable for submission. The Chinese guidelines take into consideration traditional Chinese medicines, which are usually mixtures. Likewise, the specific recommendations of India and China for the reproductive toxicity testing of chemicals and pesticides differ from those of the OECD and the USEPA. Again, studies performed in accordance with internationally recognized principles are usually acceptable for submission in both countries. The Chinese guideline for the reproductive toxicity testing of agrochemicals is currently under revision; the new version is expected to resemble more closely the requirements of the OECD and the USEPA. As a member of the OECD, India has conducted Good Laboratory Practice (GLP) inspection, accreditation, and monitoring activities since 2004. China has made several attempts to join the Council Decisions on Mutual Acceptance of Data in the Assessment of Chemicals since 2005. Currently 47 laboratories in China have been certified by the national GLP authorities. Several laboratories in China have also been recently been certified by OECD member countries as GLP compliant. In India, there are currently 23 GLP-Certified laboratories; about six of these are also AALAC accredited. The specific study designs specified in the guidelines of China and India for reproductive toxicity studies are described in detail in this chapter.

  6. Biomarker of Exposure and Mechanism of Action of Toxic Industrial Chemicals (TICs)

    DTIC Science & Technology

    2013-07-01

    primary chemicals used, 10 employee 37 samples with a rank of 1 and 10 with a rank of 6. In addition, since AN is a constituent of tobacco smoke and...toxicity of AN. First is that it can be metabolized in the body to cyanide , a well-known acute toxin. However, we have previously shown that...blocking cyanide production with inhibitors of the enzyme(s) that convert AN to cyanide does not prevent acute toxicity but only delays the time to death

  7. Environmental phototoxicity: Solar ultraviolet radiation affects the toxicity of natural and man-made chemicals

    SciTech Connect

    Larson, R.A.; Berenbaum, M.R. )

    1988-04-01

    Ultraviolet radiation appears to be toxic to all forms of unpigmented living cells, including bacteria, protozoa, nematodes, arthropods, fish, birds, and mammals. In addition to the direct absorption of solar energy by cellular constituents, toxicity may occur because of the absorption of sunlight by xenobiotics (or by naturally occurring compounds outside the target cell); these may be converted by light or by subsequent light-promoted reactions that induce cellular damage. This article describes the phototoxicity of photodynamic dyes, light-activated synthetic herbicides, petroleum and its constituents, and naturally occurring chemicals from plants. Detoxification mechanisms are also discussed.

  8. A Brine Shrimp Bioassay for Measuring Toxicity and Remediation of Chemicals

    NASA Astrophysics Data System (ADS)

    Lieberman, Marya

    1999-12-01

    A bioassay using Artemia franciscana (brine shrimp) was adapted to measure the toxicity of household chemicals. One project is described in which students collect dose-response curves for seven commercial flea-killing products. Next, groups of students researched the insecticidal ingredients of the flea products. On the basis of the structures of the active ingredients, they chose remediation methods to make the flea product less toxic to brine shrimp; procedures included copper-catalyzed hydrolysis, adsorption onto activated charcoal, bleach treatment, and photodegradation. No special equipment or supplies are necessary for the bioassay other than the brine shrimp eggs, which can be obtained at any aquarium store.

  9. Lysosomes involved in the cellular toxicity of nano-alumina: combined effects of particle size and chemical composition.

    PubMed

    Zhang, Q; Xu, L; Wang, J; Sabbioni, E; Piao, L; Di Gioacchino, M; Niu, Q

    2013-01-01

    Nowadays, manufactured nano-particles of aluminum oxide (nano-alumina) have been widely used in many fields with the rapidly developed nano-technology, but their basic toxic data are scarce. It is believed that the smaller nano-particles are able to easily cross the bio-membrane and quickly reach cellular compartments rather than micro-size particles, thus showing more toxic effects. The aim of this study was to compare the toxicity of nano- and micro- particles of alumina for detecting particle size related toxicity, and to compare the toxicity of nano-alumina and nano-carbon with the same particle size for determining chemical composition related toxicity. The present study revealed that nano-particles of alumina were much toxic than micro-alumina particles, indicating a particle size related toxicity; and were much more toxic than nano-carbon particles as well, manifesting a chemical related toxicity. The mechanism might be concerned with the involvement of the lysosomes. In conclusion, toxicity of nano-alumina is a combination of the toxic effects of its particle size and chemical composition.

  10. Variation in sensitivity of aquatic species to toxicants: Practical consequences for effect assessment of chemical substances

    SciTech Connect

    Vaal, M.A.; Van Leeuwen, C.J.; Hoekstra, J.A.; Hermens, J.L.M.

    2000-04-01

    This study addresses the relation between the sensitivity of aquatic species and mode of action of different classes or organic chemicals. The authors analyzed large data sets of ecotoxicological information to reveal the interspecies variation in sensitivity, to relate this variation to the compounds' mode of action, and to explain the observed patterns using general biological information. Here the authors present a general framework and recommendations for risk assessment procedures. The authors recommend the use of toxicologically based classification schemes at an early stage of the risk assessment procedure. Screening programs are most efficiently run when only one species per compound is tested to prioritize substances. The toxicity of compounds belonging to the class of nonpolar narcotics is highly predictable and shows little interspecies variation. For these compounds quantitative structure-activity relationships (WSARs) can be used to estimate effect levels. Most effort should be put into testing reactive compounds and compounds with a specific mode of action as toxicity to some species can be 10{sup 5}--10{sup 6} times higher compared with less sensitive species. The use of assessment factors in effect assessment procedures may lead to an underestimation of effects on the more sensitive species. For many priority pollutants there is little information on their ecotoxicity. Predictive techniques are needed to compensate for this lack of data. Knowledge of the relation between modes of action of compounds and interspecies variation in sensitivity should be integrated in risk assessment procedures in order to make more efficient use of the limited financial resources available.

  11. General baseline toxicity QSAR for nonpolar, polar and ionisable chemicals and their mixtures in the bioluminescence inhibition assay with Aliivibrio fischeri.

    PubMed

    Escher, Beate I; Baumer, Andreas; Bittermann, Kai; Henneberger, Luise; König, Maria; Kühnert, Christin; Klüver, Nils

    2017-03-22

    The Microtox assay, a bioluminescence inhibition assay with the marine bacterium Aliivibrio fischeri, is one of the most popular bioassays for assessing the cytotoxicity of organic chemicals, mixtures and environmental samples. Most environmental chemicals act as baseline toxicants in this short-term screening assay, which is typically run with only 30 min of exposure duration. Numerous Quantitative Structure-Activity Relationships (QSARs) exist for the Microtox assay for nonpolar and polar narcosis. However, typical water pollutants, which have highly diverse structures covering a wide range of hydrophobicity and speciation from neutral to anionic and cationic, are often outside the applicability domain of these QSARs. To include all types of environmentally relevant organic pollutants we developed a general baseline toxicity QSAR using liposome-water distribution ratios as descriptors. Previous limitations in availability of experimental liposome-water partition constants were overcome by reliable prediction models based on polyparameter linear free energy relationships for neutral chemicals and the COSMOmic model for charged chemicals. With this QSAR and targeted mixture experiments we could demonstrate that ionisable chemicals fall in the applicability domain. Most investigated water pollutants acted as baseline toxicants in this bioassay, with the few outliers identified as uncouplers or reactive toxicants. The main limitation of the Microtox assay is that chemicals with a high melting point and/or high hydrophobicity were outside of the applicability domain because of their low water solubility. We quantitatively derived a solubility cut-off but also demonstrated with mixture experiments that chemicals inactive on their own can contribute to mixture toxicity, which is highly relevant for complex environmental mixtures, where these chemicals may be present at concentrations below the solubility cut-off.

  12. Developing a list of reference chemicals for testing alternatives to whole fish toxicity tests.

    PubMed

    Schirmer, Kristin; Tanneberger, Katrin; Kramer, Nynke I; Völker, Doris; Scholz, Stefan; Hafner, Christoph; Lee, Lucy E J; Bols, Niels C; Hermens, Joop L M

    2008-11-11

    This paper details the derivation of a list of 60 reference chemicals for the development of alternatives to animal testing in ecotoxicology with a particular focus on fish. The chemicals were selected as a prerequisite to gather mechanistic information on the performance of alternative testing systems, namely vertebrate cell lines and fish embryos, in comparison to the fish acute lethality test. To avoid the need for additional experiments with fish, the U.S. EPA fathead minnow database was consulted as reference for whole organism responses. This database was compared to the Halle Registry of Cytotoxicity and a collation of data by the German EPA (UBA) on acute toxicity data derived from zebrafish embryos. Chemicals that were present in the fathead minnow database and in at least one of the other two databases were subject to selection. Criteria included the coverage of a wide range of toxicity and physico-chemical parameters as well as the determination of outliers of the in vivo/in vitro correlations. While the reference list of chemicals now guides our research for improving cell line and fish embryo assays to make them widely applicable, the list could be of benefit to search for alternatives in ecotoxicology in general. One example would be the use of this list to validate structure-activity prediction models, which in turn would benefit from a continuous extension of this list with regard to physico-chemical and toxicological data.

  13. Chemical and physical characteristics of cellulose insulation particulates, and evaluation of potential acute pulmonary toxicity.

    PubMed

    Morgan, Daniel L; Su, Yin-Fong; Dill, Jeffrey A; Turnier, John C; Westerberg, R Bruce; Smith, Cynthia S

    2004-12-01

    During installation of cellulose insulation (CI) in new and older houses, significant quantities of airborne material are generated. This study characterized the chemical and physical properties, and potential acute pulmonary toxicity of CI. CI from four manufacturers was analyzed for inorganic additives and trace element impurities. Aerosols were generated and size fractionated. The number and size of fibrous and nonfibrous particles in the respirable fractions were determined. Respirable CI particulates were intratracheally instilled in rats (5 mg/kg) to evaluate potential pulmonary toxicity. CI samples were similar in composition with small differences due primarily to fire retardants. Less than 0.1% of CI was respirable and contained few fibers. Acute exposure to CI caused transient inflammation in the lungs and increased 4-hydroxyproline. Microscopic evaluation revealed a minimal to mild, non-progressing granulomatous pneumonitis. Low concentrations of respirable particles were found in CI aerosols. Particles consisted primarily of fire retardants with few fibers, and caused mild pulmonary toxicity in rats.

  14. Chemical ecology of canarian laurel forest: Toxic diterpenes fromPersea indica (Lauraceae).

    PubMed

    Gonzalez-Coloma, A; Hernandez, M G; Perales, A; Fraga, B M

    1990-09-01

    The tree speciesP. indica (Lauraceae) is an important endemism in the Canary Islands laurel forest and can readily be distinguished by its defoliated appearance due to the seasonal action of wild rats (Rattus rattus), which eat the plant and become intoxicated. These observations and the phytochemical interest of this plant species led us to study the potentially toxic chemicals responsible for such action. We found that an ethanolic extract ofP. indica and its water fraction were toxic when injected into laboratory mice. The mice also died after ingestion of the stems and showed a significant preference for those extracted and rehydrated with an 8% aqueous extract solution when compared with the water control. Two compounds that have been isolated from the toxic fraction and identified by spectroscopic methods are the polyhydroxy pentacyclic diterpenes ryanodol and cinnceylanol. Possible ecological implications are discussed.

  15. The underlying toxicological mechanism of chemical mixtures: A case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum

    SciTech Connect

    Tian, Dayong; Lin, Zhifen; Zhou, Xianghong; Yin, Daqiang

    2013-10-15

    Intracellular chemical reaction of chemical mixtures is one of the main reasons that cause synergistic or antagonistic effects. However, it still remains unclear what the influencing factors on the intracellular chemical reaction are, and how they influence on the toxicological mechanism of chemical mixtures. To reveal this underlying toxicological mechanism of chemical mixtures, a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum was employed, and both their joint effects and mixture toxicity were observed. Then series of two-step linear regressions were performed to describe the relationships between joint effects, the expected additive toxicities and descriptors of individual chemicals (including concentrations, binding affinity to receptors, octanol/water partition coefficients). Based on the quantitative relationships, the underlying joint toxicological mechanisms were revealed. The result shows that, for mixtures with their joint effects resulting from intracellular chemical reaction, their underlying toxicological mechanism depends on not only their interaction with target proteins, but also their transmembrane actions and their concentrations. In addition, two generic points of toxicological mechanism were proposed including the influencing factors on intracellular chemical reaction and the difference of the toxicological mechanism between single reactive chemicals and their mixtures. This study provided an insight into the understanding of the underlying toxicological mechanism for chemical mixtures with intracellular chemical reaction. - Highlights: • Joint effects of nitriles and aldehydes at non-equitoxic ratios were determined. • A novel descriptor, ligand–receptor interaction energy (E{sub binding}), was employed. • Quantitative relationships for mixtures were developed based on a novel descriptor. • The underlying toxic mechanism was revealed based on quantitative relationships. • Two

  16. QSTR modeling for qualitative and quantitative toxicity predictions of diverse chemical pesticides in honey bee for regulatory purposes.

    PubMed

    Singh, Kunwar P; Gupta, Shikha; Basant, Nikita; Mohan, Dinesh

    2014-09-15

    Pesticides are designed toxic chemicals for specific purposes and can harm nontarget species as well. The honey bee is considered a nontarget test species for toxicity evaluation of chemicals. Global QSTR (quantitative structure-toxicity relationship) models were established for qualitative and quantitative toxicity prediction of pesticides in honey bee (Apis mellifera) based on the experimental toxicity data of 237 structurally diverse pesticides. Structural diversity of the chemical pesticides and nonlinear dependence in the toxicity data were evaluated using the Tanimoto similarity index and Brock-Dechert-Scheinkman statistics. Probabilistic neural network (PNN) and generalized regression neural network (GRNN) QSTR models were constructed for classification (two and four categories) and function optimization problems using the toxicity end point in honey bees. The predictive power of the QSTR models was tested through rigorous validation performed using the internal and external procedures employing a wide series of statistical checks. In complete data, the PNN-QSTR model rendered a classification accuracy of 96.62% (two-category) and 95.57% (four-category), while the GRNN-QSTR model yielded a correlation (R(2)) of 0.841 between the measured and predicted toxicity values with a mean squared error (MSE) of 0.22. The results suggest the appropriateness of the developed QSTR models for reliably predicting qualitative and quantitative toxicities of pesticides in honey bee. Both the PNN and GRNN based QSTR models constructed here can be useful tools in predicting the qualitative and quantitative toxicities of the new chemical pesticides for regulatory purposes.

  17. Epigenetic toxicity of environmental chemicals upon exposure during development - Bisphenol A and valproic acid may have epigenetic effects.

    PubMed

    Ideta-Otsuka, Maky; Igarashi, Katsuhide; Narita, Minoru; Hirabayashi, Yoko