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Sample records for predicting environmental chemical

  1. 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

  2. Prediction of Estrogenic Bioactivity of Environmental Chemical Metabolites.

    PubMed

    Pinto, Caroline L; Mansouri, Kamel; Judson, Richard; Browne, Patience

    2016-09-19

    The US Environmental Protection Agency's (EPA) Endocrine Disruptor Screening Program (EDSP) is using in vitro data generated from ToxCast/Tox21 high-throughput screening assays to assess the endocrine activity of environmental chemicals. Considering that in vitro assays may have limited metabolic capacity, inactive chemicals that are biotransformed into metabolites with endocrine bioactivity may be missed for further screening and testing. Therefore, there is a value in developing novel approaches to account for metabolism and endocrine activity of both parent chemicals and their associated metabolites. We used commercially available software to predict metabolites of 50 parent compounds, out of which 38 chemicals are known to have estrogenic metabolites, and 12 compounds and their metabolites are negative for estrogenic activity. Three ER QSAR models were used to determine potential estrogen bioactivity of the parent compounds and predicted metabolites, the outputs of the models were averaged, and the chemicals were then ranked based on the total estrogenicity of the parent chemical and metabolites. The metabolite prediction software correctly identified known estrogenic metabolites for 26 out of 27 parent chemicals with associated metabolite data, and 39 out of 46 estrogenic metabolites were predicted as potential biotransformation products derived from the parent chemical. The QSAR models estimated stronger estrogenic activity for the majority of the known estrogenic metabolites compared to their parent chemicals. Finally, the three models identified a similar set of parent compounds as top ranked chemicals based on the estrogenicity of putative metabolites. This proposed in silico approach is an inexpensive and rapid strategy for the detection of chemicals with estrogenic metabolites and may reduce potential false negative results from in vitro assays.

  3. Predictive environmental risk assessment of chemical mixtures: a conceptual framework.

    PubMed

    Backhaus, Thomas; Faust, Michael

    2012-03-06

    Environmental risks of chemicals are still often assessed substance-by-substance, neglecting mixture effects. This may result in risk underestimations, as the typical exposure is toward multicomponent chemical "cocktails". We use the two well established mixture toxicity concepts (Concentration Addition (CA) and Independent Action (IA)) for providing a tiered outline for environmental hazard and risk assessments of mixtures, focusing on general industrial chemicals and assuming that the "base set" of data (EC50s for algae, crustaceans, fish) is available. As mixture toxicities higher than predicted by CA are rare findings, we suggest applying CA as a precautious first tier, irrespective of the modes/mechanisms of action of the mixture components. In particular, we prove that summing up PEC/PNEC ratios might serve as a justifiable CA-approximation, in order to estimate in a first tier assessment whether there is a potential risk for an exposed ecosystem if only base-set data are available. This makes optimum use of existing single substance assessments as more demanding mixture investigations are requested only if there are first indications of an environmental risk. Finally we suggest to call for mode-of-action driven analyses only if error estimations indicate the possibility for substantial differences between CA- and IA-based assessments.

  4. 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...

  5. 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...

  6. Evaluation of a multimedia model for predicting the environmental fate of organic chemicals in Canada

    SciTech Connect

    Kane, D.M.; Mackay, D.

    1995-12-31

    Health Canada is required to assess human health risks associated with the introduction of new chemicals for commercial use in Canada. An important initial step in this assessment process is the estimation of expected concentrations of a particular new chemical in various environmental media such as air, water, sail, and sediment. These concentrations can then form the basis for subsequent calculations of human exposure. A fugacity-based multimedia exposure model (CHEMCAN3) was developed for these assessments which describes the chemical`s fate in the environment based on its physical chemical properties, reactivity, transport characteristics and emissions. This paper presents the results of a validation exercise comparing the predictions of the model against measured data. CHEMCAN3 was applied to the prediction of the environmental fate of a set of 10 organic chemicals. The predictions were then compared to available environmental monitoring data for these chemicals, The test set included 5 industrial chemicals and 5 commonly used pesticides; benzene, chlorobenzene, hexachlorobenzene, toluene, dichloromethane, di(2-ethylhexyl) phthalate, atrazine, dinoseb, lindane, parathion, and 2,4-dichlorophenoxyacetic acid. The Southern Ontario region of Canada was used as the environment for the model predictions. The results show that the model successfully predicts the environmental behavior of the chemicals, with 82% agreement within one order of magnitude between predicted and measured values. This result lends confidence to the use of this model, and similar models, for prediction of environmental fate and as a basis for exposure assessment.

  7. Predictive In Vitro Screening of Environmental Chemicals – The ToxCast Project

    EPA Science Inventory

    ToxCast, the United States Environmental Protection Agency’s chemical prioritization research program, is developing methods for utilizing computational chemistry and bioactivity profiling to predict potential for toxicity and prioritize limited testing resources (www.epa.gov/toc...

  8. Predictive In Vitro Screening of Environmental Chemicals – The ToxCast Project

    EPA Science Inventory

    ToxCast, the United States Environmental Protection Agency’s chemical prioritization research program, is developing methods for utilizing computational chemistry and bioactivity profiling to predict potential for toxicity and prioritize limited testing resources (www.epa.gov/toc...

  9. Prediction of Hydrolysis Products of Organic Chemicals under Environmental pH Conditions

    EPA Science Inventory

    Cheminformatics-based software tools can predict the molecular structure of transformation products using a library of transformation reaction schemes. This paper presents the development of such a library for abiotic hydrolysis of organic chemicals under environmentally relevant...

  10. Use of QSARs in international decision-making frameworks to predict ecologic effects and environmental fate of chemical substances.

    PubMed Central

    Cronin, Mark T D; Walker, John D; Jaworska, Joanna S; Comber, Michael H I; Watts, Christopher D; Worth, Andrew P

    2003-01-01

    This article is a review of the use, by regulatory agencies and authorities, of quantitative structure-activity relationships (QSARs) to predict ecologic effects and environmental fate of chemicals. For many years, the U.S. Environmental Protection Agency has been the most prominent regulatory agency using QSARs to predict the ecologic effects and environmental fate of chemicals. However, as increasing numbers of standard QSAR methods are developed and validated to predict ecologic effects and environmental fate of chemicals, it is anticipated that more regulatory agencies and authorities will find them to be acceptable alternatives to chemical testing. PMID:12896861

  11. A unified algorithm for predicting partition coefficients for PBPK modeling of drugs and environmental chemicals.

    PubMed

    Peyret, Thomas; Poulin, Patrick; Krishnan, Kannan

    2010-12-15

    The algorithms in the literature focusing to predict tissue:blood PC (P(tb)) for environmental chemicals and tissue:plasma PC based on total (K(p)) or unbound concentration (K(pu)) for drugs differ in their consideration of binding to hemoglobin, plasma proteins and charged phospholipids. The objective of the present study was to develop a unified algorithm such that P(tb), K(p) and K(pu) for both drugs and environmental chemicals could be predicted. The development of the unified algorithm was accomplished by integrating all mechanistic algorithms previously published to compute the PCs. Furthermore, the algorithm was structured in such a way as to facilitate predictions of the distribution of organic compounds at the macro (i.e. whole tissue) and micro (i.e. cells and fluids) levels. The resulting unified algorithm was applied to compute the rat P(tb), K(p) or K(pu) of muscle (n=174), liver (n=139) and adipose tissue (n=141) for acidic, neutral, zwitterionic and basic drugs as well as ketones, acetate esters, alcohols, aliphatic hydrocarbons, aromatic hydrocarbons and ethers. The unified algorithm reproduced adequately the values predicted previously by the published algorithms for a total of 142 drugs and chemicals. The sensitivity analysis demonstrated the relative importance of the various compound properties reflective of specific mechanistic determinants relevant to prediction of PC values of drugs and environmental chemicals. Overall, the present unified algorithm uniquely facilitates the computation of macro and micro level PCs for developing organ and cellular-level PBPK models for both chemicals and drugs.

  12. A unified algorithm for predicting partition coefficients for PBPK modeling of drugs and environmental chemicals

    SciTech Connect

    Peyret, Thomas; Poulin, Patrick; Krishnan, Kannan

    2010-12-15

    The algorithms in the literature focusing to predict tissue:blood PC (P{sub tb}) for environmental chemicals and tissue:plasma PC based on total (K{sub p}) or unbound concentration (K{sub pu}) for drugs differ in their consideration of binding to hemoglobin, plasma proteins and charged phospholipids. The objective of the present study was to develop a unified algorithm such that P{sub tb}, K{sub p} and K{sub pu} for both drugs and environmental chemicals could be predicted. The development of the unified algorithm was accomplished by integrating all mechanistic algorithms previously published to compute the PCs. Furthermore, the algorithm was structured in such a way as to facilitate predictions of the distribution of organic compounds at the macro (i.e. whole tissue) and micro (i.e. cells and fluids) levels. The resulting unified algorithm was applied to compute the rat P{sub tb}, K{sub p} or K{sub pu} of muscle (n = 174), liver (n = 139) and adipose tissue (n = 141) for acidic, neutral, zwitterionic and basic drugs as well as ketones, acetate esters, alcohols, aliphatic hydrocarbons, aromatic hydrocarbons and ethers. The unified algorithm reproduced adequately the values predicted previously by the published algorithms for a total of 142 drugs and chemicals. The sensitivity analysis demonstrated the relative importance of the various compound properties reflective of specific mechanistic determinants relevant to prediction of PC values of drugs and environmental chemicals. Overall, the present unified algorithm uniquely facilitates the computation of macro and micro level PCs for developing organ and cellular-level PBPK models for both chemicals and drugs.

  13. In Silico Prediction of Physicochemical Properties of Environmental Chemicals Using Molecular Fingerprints and Machine Learning.

    PubMed

    Zang, Qingda; Mansouri, Kamel; Williams, Antony J; Judson, Richard S; Allen, David G; Casey, Warren M; Kleinstreuer, Nicole C

    2017-01-23

    There are little available toxicity data on the vast majority of chemicals in commerce. High-throughput screening (HTS) studies, such as those being carried out by the U.S. Environmental Protection Agency (EPA) ToxCast program in partnership with the federal Tox21 research program, can generate biological data to inform models for predicting potential toxicity. However, physicochemical properties are also needed to model environmental fate and transport, as well as exposure potential. The purpose of the present study was to generate an open-source quantitative structure-property relationship (QSPR) workflow to predict a variety of physicochemical properties that would have cross-platform compatibility to integrate into existing cheminformatics workflows. In this effort, decades-old experimental property data sets available within the EPA EPI Suite were reanalyzed using modern cheminformatics workflows to develop updated QSPR models capable of supplying computationally efficient, open, and transparent HTS property predictions in support of environmental modeling efforts. Models were built using updated EPI Suite data sets for the prediction of six physicochemical properties: octanol-water partition coefficient (logP), water solubility (logS), boiling point (BP), melting point (MP), vapor pressure (logVP), and bioconcentration factor (logBCF). The coefficient of determination (R(2)) between the estimated values and experimental data for the six predicted properties ranged from 0.826 (MP) to 0.965 (BP), with model performance for five of the six properties exceeding those from the original EPI Suite models. The newly derived models can be employed for rapid estimation of physicochemical properties within an open-source HTS workflow to inform fate and toxicity prediction models of environmental chemicals.

  14. Prediction of Hydrolysis Products of Organic Chemicals under Environmental pH Conditions.

    PubMed

    Tebes-Stevens, Caroline; Patel, Jay M; Jones, W Jack; Weber, Eric J

    2017-05-02

    Cheminformatics-based software tools can predict the molecular structure of transformation products using a library of transformation reaction schemes. This paper presents the development of such a library for abiotic hydrolysis of organic chemicals under environmentally relevant conditions. The hydrolysis reaction schemes in the library encode the process science gathered from peer-reviewed literature and regulatory reports. Each scheme has been ranked on a scale of one to six based on the median half-life in a data set compiled from literature-reported hydrolysis rates. These ranks are used to predict the most likely transformation route when more than one structural fragment susceptible to hydrolysis is present in a molecule of interest. Separate rank assignments are established for pH 5, 7, and 9 to represent standard conditions in hydrolysis studies required for registration of pesticides in Organisation for Economic Co-operation and Development (OECD) member countries. The library is applied to predict the likely hydrolytic transformation products for two lists of chemicals, one representative of chemicals used in commerce and the other specific to pesticides, to evaluate which hydrolysis reaction pathways are most likely to be relevant for organic chemicals found in the natural environment.

  15. THE INTEGRATED USE OF COMPUTATIONAL CHEMISTRY, SCANNING PROBE MICROSCOPY, AND VIRTUAL REALITY TO PREDICT THE CHEMICAL REACTIVITY OF ENVIRONMENTAL SURFACES

    EPA Science Inventory

    In the last decade three new techniques scanning probe microscopy (SPM), virtual reality (YR) and computational chemistry ave emerged with the combined capability of a priori predicting the chemically reactivity of environmental surfaces. Computational chemistry provides the cap...

  16. Toxicity challenges in environmental chemicals: Prediction of human plasma protein binding through quantitative structure-activity relationship (QSAR) models

    EPA Science Inventory

    The present study explores the merit of utilizing available pharmaceutical data to construct a quantitative structure-activity relationship (QSAR) for prediction of the fraction of a chemical unbound to plasma protein (Fub) in environmentally relevant compounds. Independent model...

  17. THE INTEGRATED USE OF COMPUTATIONAL CHEMISTRY, SCANNING PROBE MICROSCOPY, AND VIRTUAL REALITY TO PREDICT THE CHEMICAL REACTIVITY OF ENVIRONMENTAL SURFACES

    EPA Science Inventory

    In the last decade three new techniques scanning probe microscopy (SPM), virtual reality (YR) and computational chemistry ave emerged with the combined capability of a priori predicting the chemically reactivity of environmental surfaces. Computational chemistry provides the cap...

  18. Toxicity challenges in environmental chemicals: Prediction of human plasma protein binding through quantitative structure-activity relationship (QSAR) models

    EPA Science Inventory

    The present study explores the merit of utilizing available pharmaceutical data to construct a quantitative structure-activity relationship (QSAR) for prediction of the fraction of a chemical unbound to plasma protein (Fub) in environmentally relevant compounds. Independent model...

  19. Importance of environmental and biomass dynamics in predicting chemical exposure in ecological risk assessment.

    PubMed

    Morselli, Melissa; Semplice, Matteo; De Laender, Frederik; Van den Brink, Paul J; Di Guardo, Antonio

    2015-09-01

    In ecological risk assessment, exposure is generally modelled assuming static conditions, herewith neglecting the potential role of emission, environmental and biomass dynamics in affecting bioavailable concentrations. In order to investigate the influence of such dynamics on predicted bioavailable concentrations, the spatially-resolved dynamic model "ChimERA fate" was developed, incorporating macrophyte and particulate/dissolved organic carbon (POC/DOC) dynamics into a water-sediment system. An evaluation against three case studies revealed a satisfying model performance. Illustrative simulations then highlighted the potential spatio-temporal variability of bioavailable concentrations after a pulsed emission of four chemicals in a system composed of a pond connected to its inflow and outflow streams. Changes in macrophyte biomass and POC/DOC levels caused exposure variations which were up to a factor of 4.5 in time and even more significant (several orders of magnitude) in space, especially for highly hydrophobic chemicals. ChimERA fate thus revealed to be a useful tool to investigate such variations and to identify those environmental and ecological conditions in which risk is expected to be highest. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. 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...

  1. 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...

  2. A Rat α-Fetoprotein Binding Activity Prediction Model to Facilitate Assessment of the Endocrine Disruption Potential of Environmental Chemicals

    PubMed Central

    Hong, Huixiao; Shen, Jie; Ng, Hui Wen; Sakkiah, Sugunadevi; Ye, Hao; Ge, Weigong; Gong, Ping; Xiao, Wenming; Tong, Weida

    2016-01-01

    Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through binding of endocrine disruptors with the hormone receptors in the target cells. Entrance of endocrine disruptors into target cells is the precondition of endocrine disruption. The binding capability of a chemical with proteins in the blood affects its entrance into the target cells and, thus, is very informative for the assessment of potential endocrine disruption of chemicals. α-fetoprotein is one of the major serum proteins that binds to a variety of chemicals such as estrogens. To better facilitate assessment of endocrine disruption of environmental chemicals, we developed a model for α-fetoprotein binding activity prediction using the novel pattern recognition method (Decision Forest) and the molecular descriptors calculated from two-dimensional structures by Mold2 software. The predictive capability of the model has been evaluated through internal validation using 125 training chemicals (average balanced accuracy of 69%) and external validations using 22 chemicals (balanced accuracy of 71%). Prediction confidence analysis revealed the model performed much better at high prediction confidence. Our results indicate that the model is useful (when predictions are in high confidence) in endocrine disruption risk assessment of environmental chemicals though improvement by increasing number of training chemicals is needed. PMID:27023588

  3. A Rat α-Fetoprotein Binding Activity Prediction Model to Facilitate Assessment of the Endocrine Disruption Potential of Environmental Chemicals.

    PubMed

    Hong, Huixiao; Shen, Jie; Ng, Hui Wen; Sakkiah, Sugunadevi; Ye, Hao; Ge, Weigong; Gong, Ping; Xiao, Wenming; Tong, Weida

    2016-03-25

    Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through binding of endocrine disruptors with the hormone receptors in the target cells. Entrance of endocrine disruptors into target cells is the precondition of endocrine disruption. The binding capability of a chemical with proteins in the blood affects its entrance into the target cells and, thus, is very informative for the assessment of potential endocrine disruption of chemicals. α-fetoprotein is one of the major serum proteins that binds to a variety of chemicals such as estrogens. To better facilitate assessment of endocrine disruption of environmental chemicals, we developed a model for α-fetoprotein binding activity prediction using the novel pattern recognition method (Decision Forest) and the molecular descriptors calculated from two-dimensional structures by Mold² software. The predictive capability of the model has been evaluated through internal validation using 125 training chemicals (average balanced accuracy of 69%) and external validations using 22 chemicals (balanced accuracy of 71%). Prediction confidence analysis revealed the model performed much better at high prediction confidence. Our results indicate that the model is useful (when predictions are in high confidence) in endocrine disruption risk assessment of environmental chemicals though improvement by increasing number of training chemicals is needed.

  4. 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 ...

  5. Essential Set of Molecular Descriptors for ADME Prediction in Drug and Environmental Chemical Space

    EPA Science Inventory

    Historically, the disciplines of pharmacology and toxicology have embraced quantitative structure-activity relationships (QSAR) and quantitative structure-property relationships (QSPR) to predict ADME properties or biological activities of untested chemicals. The question arises ...

  6. Essential Set of Molecular Descriptors for ADME Prediction in Drug and Environmental Chemical Space

    EPA Science Inventory

    Historically, the disciplines of pharmacology and toxicology have embraced quantitative structure-activity relationships (QSAR) and quantitative structure-property relationships (QSPR) to predict ADME properties or biological activities of untested chemicals. The question arises ...

  7. Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans

    EPA Pesticide Factsheets

    Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans (Presented by James McKim, Ph.D., DABT, Founder and Chief Science Officer, CeeTox) (5/25/2012)

  8. In Silico Prediction of Physicochemical Properties of Environmental Chemicals Using Molecular Fingerprints and Machine Learning

    EPA Science Inventory

    There are little available toxicity data on the vast majority of chemicals in commerce. High-throughput screening (HTS) studies, such as those being carried out by the U.S. Environmental Protection Agency (EPA) ToxCast program in partnership with the federal Tox21 research progra...

  9. 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 ...

  10. 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 ...

  11. An Online Prediction Platform to Support the Environmental Sciences (American Chemical Society)

    EPA Science Inventory

    Historical QSAR models are currently utilized across a broad range of applications within the U.S. Environmental Protection Agency (EPA). These models predict basic physicochemical properties (e.g., logP, aqueous solubility, vapor pressure), which are then incorporated into expo...

  12. An Online Prediction Platform to Support the Environmental Sciences (American Chemical Society)

    EPA Science Inventory

    Historical QSAR models are currently utilized across a broad range of applications within the U.S. Environmental Protection Agency (EPA). These models predict basic physicochemical properties (e.g., logP, aqueous solubility, vapor pressure), which are then incorporated into expo...

  13. From consumption to harvest: Environmental fate prediction of excreted ionizable trace organic chemicals.

    PubMed

    Polesel, Fabio; Plósz, Benedek Gy; Trapp, Stefan

    2015-11-01

    Excreted trace organic chemicals, e.g., pharmaceuticals and biocides, typically undergo incomplete elimination in municipal wastewater treatment plants (WWTPs) and are released to surface water via treated effluents and to agricultural soils through sludge amendment and/or irrigation with freshwater or reclaimed wastewater. Recent research has shown the tendency for these substances to accumulate in food crops. In this study, we developed and applied a simulation tool to predict the fate of three ionizable trace chemicals (triclosan-TCS, furosemide-FUR, ciprofloxacin-CIP) from human consumption/excretion up to the accumulation in soil and plant, following field amendment with sewage sludge or irrigation with river water (assuming dilution of WWTP effluent). The simulation tool combines the SimpleTreat model modified for fate prediction of ionizable chemicals in a generic WWTP and a recently developed dynamic soil-plant uptake model. The simulation tool was tested using country-specific (e.g., consumption/emission rates, precipitation and temperature) input data. A Monte Carlo-based approach was adopted to account for the uncertainty associated to physico-chemical and biokinetic model parameters. Results obtained in this study suggest significant accumulation of TCS and CIP in sewage sludge (1.4-2.8 mg kgDW(-1)) as compared to FUR (0.02-0.11 mg kgDW(-1)). For the latter substance, more than half of the influent load (60.1%-72.5%) was estimated to be discharged via WWTP effluent. Specific emission rates (g ha(-1) a(-1)) of FUR to soil via either sludge application or irrigation were up to 300 times lower than for TCS and CIP. Nevertheless, high translocation potential to wheat was predicted for FUR, reaching concentrations up to 4.3 μg kgDW(-1) in grain. Irrigation was found to enhance the relative translocation of FUR to plant (45.3%-48.9% of emission to soil), as compared to sludge application (21.9%-27.6%). A comparison with peer-reviewed literature showed

  14. Chemical and Environmental Technology.

    ERIC Educational Resources Information Center

    Sheather, Harry

    The two-year curriculum in chemical technology presented in the document is designed to prepare high school graduates for technical positions in the chemical industry. Course outlines are given for general chemistry, chemical calculations, quantitative analysis, environmental chemistry, organic chemistry 1 and 2, instrumental analysis, and…

  15. Environmental toxicological fate prediction of diverse organic chemicals based on steady-state compartmental chemical mass ratio using quantitative structure-fate relationship (QSFR) models.

    PubMed

    Pramanik, Subrata; Roy, Kunal

    2013-07-01

    Four quantitative prediction models for steady-state compartmental chemical mass concentrations (Wn,g) were obtained from structural information, physiochemical properties, degradation rate and transport coefficients of 455 diverse organic chemicals using chemometric tools in a quantitative structure-fate relationship (QSFR) study. The mass ratio assessment of environmentally prevalent organic chemicals may be helpful to predict their toxicological fate in the ecosystems. Four sets of mass ratios [(1) log(Wair) from water emissions (water to air compartment), (2) log(Wair) from air emissions (within different zones of the air compartment), (3) log(Wwater) from water emissions (within different zones of the water compartment) and (4) log(Wwater) from air emissions (air to water compartment)] have been used. The developed models using genetic function approximation followed by multiple linear regression (GFA-MLR) and subsequent partial least squares (PLS) treatment identify only four descriptors for log(Wair) from water emission, six descriptors for log(Wair) from air emission, five descriptors for log(Wwater) from water emission and seven descriptors for log(Wwater) from air emission for predicting efficiently a large number of test set chemicals (ntest=182). The conclusive models suggest that descriptors such as partition coefficients (Kaw, Kow and Ksw), degradation parameters (Ksoil,Kwater and Kair), vapor pressure (Pv), diffusivity (Dwater), spatial descriptors (Jurs-WNSA-1, Jurs-WNSA-2, Jurs-WPSA-3, Jurs-FNSA-3 and Density), thermodynamic descriptors (MolRef and AlogP98), electrotopological state indices (S_dsN, S_ssNH and S_dsCH) are important for predicting the chemical mass ratios. The developed models may be applicable in toxicological fate prediction of diverse chemicals in the ecosystems.

  16. The Environmental Fate Simulator: A tool for predicting the degradation pathways of organic chemicals in groundwater aquifers

    EPA Science Inventory

    Development of the Environmental Fate Simulator (EFS): • High throughput computational system for providing molecular and environmental descriptors for consumption by EF&T models Requires:  Knowledge of the process science controlling chemical fate and transport  The abil...

  17. The Environmental Fate Simulator: A tool for predicting the degradation pathways of organic chemicals in groundwater aquifers

    EPA Science Inventory

    Development of the Environmental Fate Simulator (EFS): • High throughput computational system for providing molecular and environmental descriptors for consumption by EF&T models Requires:  Knowledge of the process science controlling chemical fate and transport  The abil...

  18. In Silico Prediction of Toxicokinetic Parameters for Environmentally Relevant Chemicals for Risk-Based Prioritization

    EPA Science Inventory

    Toxicokinetic (TK) models can address an important component of chemical risk assessments by helping bridge the gap between chemical exposure and measured toxicity endpoints. The metabolic clearance rate (CLint) and fraction of a chemical unbound by plasma proteins (Fub) are crit...

  19. Prediction of hydrolysis pathways and kinetics for antibiotics under environmental pH conditions: a quantum chemical study on cephradine.

    PubMed

    Zhang, Haiqin; Xie, Hongbin; Chen, Jingwen; Zhang, Shushen

    2015-02-03

    Understanding hydrolysis pathways and kinetics of many antibiotics that have multiple hydrolyzable functional groups is important for their fate assessment. However, experimental determination of hydrolysis encounters difficulties due to time and cost restraint. We employed the density functional theory and transition state theory to predict the hydrolysis pathways and kinetics of cephradine, a model of cephalosporin with two hydrolyzable groups, two ionization states, two isomers and two nucleophilic attack directions. Results showed that the hydrolysis of cephradine at pH = 8.0 proceeds via opening of the β-lactam ring followed by intramolecular amidation. The predicted rate constants at different pH conditions are of the same order of magnitude as the experimental values, and the predicted products are confirmed by experiment. This study identified a catalytic role of the carboxyl group in the hydrolysis, and implies that the carboxyl group also plays a catalytic role in the hydrolysis of other cephalosporin and penicillin antibiotics. This is a first attempt to quantum chemically predict hydrolysis of an antibiotic with complex pathways, and indicates that to predict hydrolysis products under the environmental pH conditions, the variation of the rate constants for different pathways with pH should be evaluated.

  20. Prediction of Cytochrome P450 Profiles of Environmental Chemicals with QSAR Models Built from Drug-like Molecules

    EPA Science Inventory

    The human cytochrome P450 (CYP450) enzyme family is involved in the biotransformation of many environmental chemicals. As part of the U.S. Tox21 effort, we profiled the CYP450 activity of ~2800 chemicals predominantly of environmental concern against CYP1A2, CYP2C19, CYP2C9, CYP2...

  1. Prediction of Cytochrome P450 Profiles of Environmental Chemicals with QSAR Models Built from Drug-like Molecules

    EPA Science Inventory

    The human cytochrome P450 (CYP450) enzyme family is involved in the biotransformation of many environmental chemicals. As part of the U.S. Tox21 effort, we profiled the CYP450 activity of ~2800 chemicals predominantly of environmental concern against CYP1A2, CYP2C19, CYP2C9, CYP2...

  2. Application of Quantum Chemical Approximations to Environmental Problems: Prediction of Water Solubility for Nitro Compounds

    DTIC Science & Technology

    2009-11-10

    V Laboratory of Theoretical Chemistry, Department of Molecular Structure, A.V. Bogatsky Physical-Chemical Institute, National Academy of Sciences of...Academy of Sciences of Ukraine, Odessa, Ukraine V I C T O R E . K U Z ’ M I N Laboratory of Theoretical Chemistry, Department of Molecular Structure...A.V. Bogatsky Physical-Chemical Institute, National Academy of Sciences of Ukraine, Odessa, Ukraine M O H A M M A D Q A S I M U.S. Army ERDC, Vicksburg

  3. 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.

  4. Epigenetics and environmental chemicals

    PubMed Central

    Baccarelli, A; Bollati, V.

    2011-01-01

    Purpose of the review Epigenetics investigates heritable changes in gene expression occurring without changes in DNA sequence. Several epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA (miRNA) expression, can change genome function under exogenous influence. Here, we review current evidence indicating that epigenetic alterations mediate toxicity from environmental chemicals. Recent findings In-vitro, animal, and human investigations have identified several classes of environmental chemicals that modify epigenetic marks, including metals (cadmium, arsenic, nickel, chromium, methylmercury), peroxisome proliferators (trichloroethylene, dichloroacetic acid, trichloroacetic acid), air pollutants (particulate matter, black carbon, benzene), and endocrine-disrupting/reproductive toxicants (diethylstilbestrol, bisphenol A, persistent organic pollutants, dioxin). Most studies conducted so far have been centered on DNA methylation, whereas only a few investigations have studied environmental chemicals in relation to histone modications and miRNA. Summary For several exposures, it has been proved that chemicals can alter epigenetic marks and that the same or similar epigenetic alterations can be found in patients with the disease of concern or in diseased tissues. Future prospective investigations are needed to determine whether exposed subjects develop epigenetic alterations over time and, in turn, which such alterations increase the risk of disease. Also, further research is needed to determine whether environmental epigenetic changes are transmitted transgenerationally. PMID:19663042

  5. Informing the Human Plasma Protein Binding of Environmental Chemicals by Machine Learning in the Pharmaceutical Space: Applicability Domain and Limits of Predictability.

    PubMed

    Ingle, Brandall L; Veber, Brandon C; Nichols, John W; Tornero-Velez, Rogelio

    2016-11-28

    The free fraction of a xenobiotic in plasma (Fub) is an important determinant of chemical adsorption, distribution, metabolism, elimination, and toxicity, yet experimental plasma protein binding data are scarce for environmentally relevant chemicals. The presented work explores the merit of utilizing available pharmaceutical data to predict Fub for environmentally relevant chemicals via machine learning techniques. Quantitative structure-activity relationship (QSAR) models were constructed with k nearest neighbors (kNN), support vector machines (SVM), and random forest (RF) machine learning algorithms from a training set of 1045 pharmaceuticals. The models were then evaluated with independent test sets of pharmaceuticals (200 compounds) and environmentally relevant ToxCast chemicals (406 total, in two groups of 238 and 168 compounds). The selection of a minimal feature set of 10-15 2D molecular descriptors allowed for both informative feature interpretation and practical applicability domain assessment via a bounded box of descriptor ranges and principal component analysis. The diverse pharmaceutical and environmental chemical sets exhibit similarities in terms of chemical space (99-82% overlap), as well as comparable bias and variance in constructed learning curves. All the models exhibit significant predictability with mean absolute errors (MAE) in the range of 0.10-0.18Fub. The models performed best for highly bound chemicals (MAE 0.07-0.12), neutrals (MAE 0.11-0.14), and acids (MAE 0.14-0.17). A consensus model had the highest accuracy across both pharmaceuticals (MAE 0.151-0.155) and environmentally relevant chemicals (MAE 0.110-0.131). The inclusion of the majority of the ToxCast test sets within the AD of the consensus model, coupled with high prediction accuracy for these chemicals, indicates the model provides a QSAR for Fub that is broadly applicable to both pharmaceuticals and environmentally relevant chemicals.

  6. Coal Extraction - Environmental Prediction

    USGS Publications Warehouse

    Cecil, C. Blaine; Tewalt, Susan J.

    2002-01-01

    Coal from the Appalachian region has supplied energy to the Nation for more than 200 years. Appalachian coal fueled America through a civil war and helped win two world wars. Appalachian coal has also provided fuel for keeping America warm in the winter and cool in the summer and has served as the basis for the steel, automobile, organic chemicals, chlorine, and aluminum industries. These benefits have not come without environmental costs, however. Coal extraction and utilization have had significant environmental impacts.

  7. Environmental Chemicals in Breast Milk

    EPA Science Inventory

    Most of the information available on environmental chemicals in breast milk is focused on persistent, lipophilic chemicals; the database on levels of these chemicals has expanded substantially since the 1950s. Currently, various types of chemicals are measured in breast milk and ...

  8. Environmental Chemicals in Breast Milk

    EPA Science Inventory

    Most of the information available on environmental chemicals in breast milk is focused on persistent, lipophilic chemicals; the database on levels of these chemicals has expanded substantially since the 1950s. Currently, various types of chemicals are measured in breast milk and ...

  9. Prediction of Cytochrome P450 Profiles of Environmental Chemicals with QSAR Models Built from Drug-like Molecules

    PubMed Central

    Sun, Hongmao; Veith, Henrike; Xia, Menghang; Austin, Christopher P.; Tice, Raymond R.; Huang, Ruili

    2012-01-01

    The human cytochrome P450 (CYP) enzyme family is involved in the biotransformation of many xenobiotics. As part of the U.S. Tox21 Phase I effort, we profiled the CYP activity of approximately three thousand compounds, primarily those of environmental concern, against human CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4 isoforms in a quantitative high throughput screening (qHTS) format. In order to evaluate the extent to which computational models built from a drug-like library screened in these five CYP assays under the same conditions can accurately predict the outcome of an environmental compound library, five support vector machines (SVM) models built from over 17,000 drug-like compounds were challenged to predict the CYP activities of the Tox21 compound collection. Although a large fraction of the test compounds fall outside of the applicability domain (AD) of the models, as measured by k-nearest neighbor (k-NN) similarities, the predictions were largely accurate for CYP1A2, CYP2C9, and CYP3A4 ioszymes with area under the receiver operator characteristic curves (AUC-ROC) ranging between 0.82 and 0.84. The lower predictive power of the CYP2C19 model (AUC-ROC = 0.76) is caused by experimental errors and that of the CYP2D6 model (AUC-ROC = 0.76) can be rescued by rebalancing the training data. Our results demonstrate that decomposing molecules into atom types enhanced the coverage of the AD and that computational models built from drug-like molecules can be used to predict the ability of non-drug like compounds to interact with these CYPs. PMID:23459712

  10. Predicting biological effects of environmental mixtures using exposure:activity ratios (EAR) derived from US EPA’s ToxCast data: Retrospective application to chemical monitoring data

    EPA Science Inventory

    Chemical monitoring has been widely used in environmental surveillance to assess exposure to environmental contaminants which could represent potential hazards to exposed organisms. However, the ability to detect chemicals in the environment has rapidly outpaced assessment of pot...

  11. Predicting biological effects of environmental mixtures using exposure:activity ratios (EAR) derived from US EPA’s ToxCast data: Retrospective application to chemical monitoring data

    EPA Science Inventory

    Chemical monitoring has been widely used in environmental surveillance to assess exposure to environmental contaminants which could represent potential hazards to exposed organisms. However, the ability to detect chemicals in the environment has rapidly outpaced assessment of pot...

  12. Predictive testing of environmental carcinogens

    SciTech Connect

    Dickson, J.G.

    1982-01-01

    Two research approaches are presented which address different aspects of predictive testing for environmental carcinogens. In Part I, a well-known microbial assay is used to determine the presence of carcinogens in an environmental sample of suspected hazard. In Part II, a single chemical carcinogen is chosen to demonstrate the utility of three-phase microcosms for prediction of transport and transformations pathways in a reservoir ecosystem. The Ames/Salmonella mutagenicity assay was used to screen processed oil shale extracts for potentially carcinogenic chemicals. Positive mutagenic activity was detected in organic solvent extracts of all four spent shales tested. Problems which might limit application of the Ames assay were explored. The results of assays of one-to-one mixtures of two mutagens which exhibited different dose response curves when assayed separately indicated the response to the mixture was nonadditive. Furthermore, the response to the mixture was determined to be statistically indistinguishable (chi-square analysis) from the dose response curve of one of the mutagens in the majority of cases. This masking effect was found to persist for one strong mutagen (benzo(a)pyrene) even when it composed only 10% of the mixture. The effect of various non-toxic solvents on the mutagenic response of certain mutagens was also determined. Three-phase microcosms were used to study the aquatic fate and effect of a polycyclic aromatic hydrocarbon (PAH), benz(a)antracene.

  13. Toxicokinetic Triage for Environmental Chemicals

    PubMed Central

    Wambaugh, John F.; Wetmore, Barbara A.; Pearce, Robert; Strope, Cory; Goldsmith, Rocky; Sluka, James P.; Sedykh, Alexander; Tropsha, Alex; Bosgra, Sieto; Shah, Imran; Judson, Richard; Thomas, Russell S.; Woodrow Setzer, R.

    2015-01-01

    Toxicokinetic (TK) models link administered doses to plasma, blood, and tissue concentrations. High-throughput TK (HTTK) performs in vitro to in vivo extrapolation to predict TK from rapid in vitro measurements and chemical structure-based properties. A significant toxicological application of HTTK has been “reverse dosimetry,” in which bioactive concentrations from in vitro screening studies are converted into in vivo doses (mg/kg BW/day). These doses are predicted to produce steady-state plasma concentrations that are equivalent to in vitro bioactive concentrations. In this study, we evaluate the impact of the approximations and assumptions necessary for reverse dosimetry and develop methods to determine whether HTTK tools are appropriate or may lead to false conclusions for a particular chemical. Based on literature in vivo data for 87 chemicals, we identified specific properties (eg, in vitro HTTK data, physico-chemical descriptors, and predicted transporter affinities) that correlate with poor HTTK predictive ability. For 271 chemicals we developed a generic HT physiologically based TK (HTPBTK) model that predicts non-steady-state chemical concentration time-courses for a variety of exposure scenarios. We used this HTPBTK model to find that assumptions previously used for reverse dosimetry are usually appropriate, except most notably for highly bioaccumulative compounds. For the thousands of man-made chemicals in the environment that currently have no TK data, we propose a 4-element framework for chemical TK triage that can group chemicals into 7 different categories associated with varying levels of confidence in HTTK predictions. For 349 chemicals with literature HTTK data, we differentiated those chemicals for which HTTK approaches are likely to be sufficient, from those that may require additional data. PMID:26085347

  14. Toxicokinetic Triage for Environmental Chemicals.

    PubMed

    Wambaugh, John F; Wetmore, Barbara A; Pearce, Robert; Strope, Cory; Goldsmith, Rocky; Sluka, James P; Sedykh, Alexander; Tropsha, Alex; Bosgra, Sieto; Shah, Imran; Judson, Richard; Thomas, Russell S; Setzer, R Woodrow

    2015-09-01

    Toxicokinetic (TK) models link administered doses to plasma, blood, and tissue concentrations. High-throughput TK (HTTK) performs in vitro to in vivo extrapolation to predict TK from rapid in vitro measurements and chemical structure-based properties. A significant toxicological application of HTTK has been "reverse dosimetry," in which bioactive concentrations from in vitro screening studies are converted into in vivo doses (mg/kg BW/day). These doses are predicted to produce steady-state plasma concentrations that are equivalent to in vitro bioactive concentrations. In this study, we evaluate the impact of the approximations and assumptions necessary for reverse dosimetry and develop methods to determine whether HTTK tools are appropriate or may lead to false conclusions for a particular chemical. Based on literature in vivo data for 87 chemicals, we identified specific properties (eg, in vitro HTTK data, physico-chemical descriptors, and predicted transporter affinities) that correlate with poor HTTK predictive ability. For 271 chemicals we developed a generic HT physiologically based TK (HTPBTK) model that predicts non-steady-state chemical concentration time-courses for a variety of exposure scenarios. We used this HTPBTK model to find that assumptions previously used for reverse dosimetry are usually appropriate, except most notably for highly bioaccumulative compounds. For the thousands of man-made chemicals in the environment that currently have no TK data, we propose a 4-element framework for chemical TK triage that can group chemicals into 7 different categories associated with varying levels of confidence in HTTK predictions. For 349 chemicals with literature HTTK data, we differentiated those chemicals for which HTTK approaches are likely to be sufficient, from those that may require additional data.

  15. Informing the Human Plasma Protein Binding of Environmental Chemicals by Machine Learning in the Pharmaceutical Space: Applicability Domain and Limits of Predictability

    EPA Science Inventory

    The free fraction of a xenobiotic in plasma (Fub) is an important determinant of chemical adsorption, distribution, metabolism, elimination, and toxicity, yet experimental plasma protein binding data is scarce for environmentally relevant chemicals. The presented work explores th...

  16. Informing the Human Plasma Protein Binding of Environmental Chemicals by Machine Learning in the Pharmaceutical Space: Applicability Domain and Limits of Predictability

    EPA Science Inventory

    The free fraction of a xenobiotic in plasma (Fub) is an important determinant of chemical adsorption, distribution, metabolism, elimination, and toxicity, yet experimental plasma protein binding data is scarce for environmentally relevant chemicals. The presented work explores th...

  17. Environmental chemical exposures and human epigenetics

    PubMed Central

    Hou, Lifang; Zhang, Xiao; Wang, Dong; Baccarelli, Andrea

    2012-01-01

    Every year more than 13 million deaths worldwide are due to environmental pollutants, and approximately 24% of diseases are caused by environmental exposures that might be averted through preventive measures. Rapidly growing evidence has linked environmental pollutants with epigenetic variations, including changes in DNA methylation, histone modifications and microRNAs. Environ mental chemicals and epigenetic changes All of these mechanisms are likely to play important roles in disease aetiology, and their modifications due to environmental pollutants might provide further understanding of disease aetiology, as well as biomarkers reflecting exposures to environmental pollutants and/or predicting the risk of future disease. We summarize the findings on epigenetic alterations related to environmental chemical exposures, and propose mechanisms of action by means of which the exposures may cause such epigenetic changes. We discuss opportunities, challenges and future directions for future epidemiology research in environmental epigenomics. Future investigations are needed to solve methodological and practical challenges, including uncertainties about stability over time of epigenomic changes induced by the environment, tissue specificity of epigenetic alterations, validation of laboratory methods, and adaptation of bioinformatic and biostatistical methods to high-throughput epigenomics. In addition, there are numerous reports of epigenetic modifications arising following exposure to environmental toxicants, but most have not been directly linked to disease endpoints. To complete our discussion, we also briefly summarize the diseases that have been linked to environmental chemicals-related epigenetic changes. PMID:22253299

  18. Human health and the environment: Predicting plasma protein binding and metabolic clearance rates of environmentally relevant chemicals.

    EPA Science Inventory

    In silico methods provide a rapid, inexpensive means of screening a wide array of environmentally relevant pollutants, pesticides, fungicides and consumer products for further toxicity testing. Physiologically based pharmacokinetic (PBPK) models bridge the gap between in vitro as...

  19. Human health and the environment: Predicting plasma protein binding and metabolic clearance rates of environmentally relevant chemicals.

    EPA Science Inventory

    In silico methods provide a rapid, inexpensive means of screening a wide array of environmentally relevant pollutants, pesticides, fungicides and consumer products for further toxicity testing. Physiologically based pharmacokinetic (PBPK) models bridge the gap between in vitro as...

  20. Predicted no effect concentration derivation as a significant source of variability in environmental hazard assessments of chemicals in aquatic systems: an international analysis.

    PubMed

    Hahn, Thorsten; Diamond, Jerry; Dobson, Stuart; Howe, Paul; Kielhorn, Janet; Koennecker, Gustav; Lee-Steere, Chris; Mangelsdorf, Inge; Schneider, Uwe; Sugaya, Yoshio; Taylor, Ken; Dam, Rick Van; Stauber, Jenny L

    2014-01-01

    Environmental hazard assessments for chemicals are carried out to define an environmentally "safe" level at which, theoretically, the chemical will not negatively affect any exposed biota. Despite this common goal, the methodologies in use are very diverse across different countries and jurisdictions. This becomes particularly obvious when international scientists work together on documents with global scope, e.g., in the World Health Organization (WHO) International Program on Chemical Safety. In this article, we present a study that describes the extent of such variability and analyze the reasons that lead to different outcomes in deriving a "safe level" (termed the predicted no effect concentration [PNEC] throughout this article). For this purpose, we chose 5 chemicals to represent well-known substances for which sufficient high-quality aquatic effects data were available: ethylene glycol, trichloroethylene, nonylphenol, hexachlorobenzene, and copper (Cu). From these data, 2 data sets for each chemical were compiled: the full data set, that contained all information from selected peer-review sources, and the base data set, a subsample of the full set simulating limited data. Scientists from the European Union (EU), United States, Canada, Japan, and Australia independently carried out hazard assessments for each of these chemicals using the same data sets. Their reasoning for key study selection, use of assessment factors, or use of probabilistic methods was comprehensively documented. The observed variation in the PNECs for all chemicals was up to 3 orders of magnitude, and this was not simply due to obvious factors such as the size of the data set or the methodology used. Rather, this was due to individual decisions of the assessors within the scope of the methodology used, especially key study selection, acute versus chronic definitions, and size of assessment factors. Awareness of these factors, together with transparency of the decision-making process, would

  1. Assessment of in vitro high throughput pharmacokinetic data to predict in vivo pharmacokinetic data of environmental chemicals

    EPA Science Inventory

    Assessing the health risks of the thousands of chemicals in use requires both toxicology and pharmacokinetic (PK) data that can be generated more quickly. For PK, in vitro clearance assays with hepatocytes and serum protein binding assays provide a means to generate high throughp...

  2. Assessment of in vitro high throughput pharmacokinetic data to predict in vivo pharmacokinetic data of environmental chemicals

    EPA Science Inventory

    Assessing the health risks of the thousands of chemicals in use requires both toxicology and pharmacokinetic (PK) data that can be generated more quickly. For PK, in vitro clearance assays with hepatocytes and serum protein binding assays provide a means to generate high throughp...

  3. Environmental benefits of chemical propulsion

    NASA Technical Reports Server (NTRS)

    Hayes, Joyce A.; Goldberg, Benjamin E.; Anderson, David M.

    1995-01-01

    This paper identifies the necessity of chemical propulsion to satellite usage and some of the benefits accrued through monitoring global resources and patterns, including the Global Climate Change Model (GCM). The paper also summarized how the satellite observations are used to affect national and international policies. Chemical propulsion, like all environmentally conscious industries, does provide limited, controlled pollutant sources through its manufacture and usage. However, chemical propulsion is the sole source which enables mankind to launch spacecraft and monitor the Earth. The information provided by remote sensing directly affects national and international policies designed to protect the environment and enhance the overall quality of life on Earth. The resultant of chemical propulsion is the capability to reduce overall pollutant emissions to the benefit of mankind.

  4. Toxicokinetic Triage for Environmental Chemicals

    EPA Science Inventory

    Toxicokinetic (TK) models are essential for linking administered doses to blood and tissue concentrations. In vitro-to-in vivo extrapolation (IVIVE) methods have been developed to determine TK from limited in vitro measurements and chemical structure-based property predictions, p...

  5. Toxicokinetic Triage for Environmental Chemicals

    EPA Science Inventory

    Toxicokinetic (TK) models are essential for linking administered doses to blood and tissue concentrations. In vitro-to-in vivo extrapolation (IVIVE) methods have been developed to determine TK from limited in vitro measurements and chemical structure-based property predictions, p...

  6. Chemical-gene interaction networks and causal reasoning for biological effects prediction and prioritization of contaminants for environmental monitoring and surveillance

    EPA Science Inventory

    Evaluating the potential human health and ecological risks associated with exposures to complex chemical mixtures in the environment is one of the main challenges of chemical safety assessment and environmental protection. There is a need for approaches that can help to integrat...

  7. Chemical-gene interaction networks and causal reasoning for biological effects prediction and prioritization of contaminants for environmental monitoring and surveillance

    EPA Science Inventory

    Evaluating the potential human health and ecological risks associated with exposures to complex chemical mixtures in the environment is one of the main challenges of chemical safety assessment and environmental protection. There is a need for approaches that can help to integrat...

  8. Prediction of Chemical Function: Model Development and ...

    EPA Pesticide Factsheets

    The United States Environmental Protection Agency’s Exposure Forecaster (ExpoCast) project is developing both statistical and mechanism-based computational models for predicting exposures to thousands of chemicals, including those in consumer products. The high-throughput (HT) screening-level exposures developed under ExpoCast can be combined with HT screening (HTS) bioactivity data for the risk-based prioritization of chemicals for further evaluation. The functional role (e.g. solvent, plasticizer, fragrance) that a chemical performs can drive both the types of products in which it is found and the concentration in which it is present and therefore impacting exposure potential. However, critical chemical use information (including functional role) is lacking for the majority of commercial chemicals for which exposure estimates are needed. A suite of machine-learning based models for classifying chemicals in terms of their likely functional roles in products based on structure were developed. This effort required collection, curation, and harmonization of publically-available data sources of chemical functional use information from government and industry bodies. Physicochemical and structure descriptor data were generated for chemicals with function data. Machine-learning classifier models for function were then built in a cross-validated manner from the descriptor/function data using the method of random forests. The models were applied to: 1) predict chemi

  9. Prediction of Chemical Function: Model Development and ...

    EPA Pesticide Factsheets

    The United States Environmental Protection Agency’s Exposure Forecaster (ExpoCast) project is developing both statistical and mechanism-based computational models for predicting exposures to thousands of chemicals, including those in consumer products. The high-throughput (HT) screening-level exposures developed under ExpoCast can be combined with HT screening (HTS) bioactivity data for the risk-based prioritization of chemicals for further evaluation. The functional role (e.g. solvent, plasticizer, fragrance) that a chemical performs can drive both the types of products in which it is found and the concentration in which it is present and therefore impacting exposure potential. However, critical chemical use information (including functional role) is lacking for the majority of commercial chemicals for which exposure estimates are needed. A suite of machine-learning based models for classifying chemicals in terms of their likely functional roles in products based on structure were developed. This effort required collection, curation, and harmonization of publically-available data sources of chemical functional use information from government and industry bodies. Physicochemical and structure descriptor data were generated for chemicals with function data. Machine-learning classifier models for function were then built in a cross-validated manner from the descriptor/function data using the method of random forests. The models were applied to: 1) predict chemi

  10. Coal extraction - environmental prediction

    SciTech Connect

    C. Blaine Cecil; Susan J. Tewalt

    2002-08-01

    To predict and help minimize the impact of coal extraction in the Appalachian region, the U.S. Geological Survey (USGS) is addressing selected mine-drainage issues through the following four interrelated studies: spatial variability of deleterious materials in coal and coal-bearing strata; kinetics of pyrite oxidation; improved spatial geologic models of the potential for drainage from abandoned coal mines; and methodologies for the remediation of waters discharged from coal mines. As these goals are achieved, the recovery of coal resources will be enhanced. 2 figs.

  11. High-Throughput Pharmacokinetics for Environmental Chemicals (SOT)

    EPA Science Inventory

    High throughput screening (HTS) promises to allow prioritization of thousands of environmental chemicals with little or no in vivo information. For bioactivity identified by HTS, toxicokinetic (TK) models are essential to predict exposure thresholds below which no significant bio...

  12. 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...

  13. High-Throughput Pharmacokinetics for Environmental Chemicals (SOT)

    EPA Science Inventory

    High throughput screening (HTS) promises to allow prioritization of thousands of environmental chemicals with little or no in vivo information. For bioactivity identified by HTS, toxicokinetic (TK) models are essential to predict exposure thresholds below which no significant bio...

  14. 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...

  15. Prediction of Chemical Function: Model Development and Application

    EPA Science Inventory

    The United States Environmental Protection Agency’s Exposure Forecaster (ExpoCast) project is developing both statistical and mechanism-based computational models for predicting exposures to thousands of chemicals, including those in consumer products. The high-throughput (...

  16. Prediction of Chemical Function: Model Development and Application

    EPA Science Inventory

    The United States Environmental Protection Agency’s Exposure Forecaster (ExpoCast) project is developing both statistical and mechanism-based computational models for predicting exposures to thousands of chemicals, including those in consumer products. The high-throughput (...

  17. ENVIRONMENTAL ENGINEERING AND ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Endocrine disruptors are a class of chemicals of growing interest to the environmental community. USEPA's Risk Assessment Forum defined an endocrine disrupting chemical (EDC) as "an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or elim...

  18. ENVIRONMENTAL ENGINEERING AND ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Endocrine disruptors are a class of chemicals of growing interest to the environmental community. USEPA's Risk Assessment Forum defined an endocrine disrupting chemical (EDC) as "an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or elim...

  19. Prediction of rodent carcinogenicity for 30 chemicals

    SciTech Connect

    Ashby, J.

    1996-10-01

    Predictions of carcinogenic activity are made for 30 chemicals currently being assessed for rodent carcinogenicity by the U.S. National Toxicology Program. The predictions are based upon the chemical structure, the anticipated or reported mutagenicity, and the reported sub-chronic toxicity of each chemical. It is predicted that 13 chemicals will be noncarcinogenic to rodents, that 7 will be genotoxic carcinogens, and that 10 may show some evidence of presumed nongenotoxic rodent carcinogenesis. 3 refs., 1 fig.

  20. Integrating Biological and Chemical Data for Hepatotoxicity Prediction (SOT)

    EPA Science Inventory

    The U.S. EPA ToxCastTM program is screening thousands of environmental chemicals for bioactivity using hundreds of high-throughput in vitro assays to build predictive models of toxicity. A set of 677 chemicals were represented by 711 bioactivity descriptors (from ToxCast assays),...

  1. Integrating Biological and Chemical Data for Hepatotoxicity Prediction (SOT)

    EPA Science Inventory

    The U.S. EPA ToxCastTM program is screening thousands of environmental chemicals for bioactivity using hundreds of high-throughput in vitro assays to build predictive models of toxicity. A set of 677 chemicals were represented by 711 bioactivity descriptors (from ToxCast assays),...

  2. Learning to predict chemical reactions.

    PubMed

    Kayala, Matthew A; Azencott, Chloé-Agathe; Chen, Jonathan H; Baldi, Pierre

    2011-09-26

    Being able to predict the course of arbitrary chemical reactions is essential to the theory and applications of organic chemistry. Approaches to the reaction prediction problems can be organized around three poles corresponding to: (1) physical laws; (2) rule-based expert systems; and (3) inductive machine learning. Previous approaches at these poles, respectively, are not high throughput, are not generalizable or scalable, and lack sufficient data and structure to be implemented. We propose a new approach to reaction prediction utilizing elements from each pole. Using a physically inspired conceptualization, we describe single mechanistic reactions as interactions between coarse approximations of molecular orbitals (MOs) and use topological and physicochemical attributes as descriptors. Using an existing rule-based system (Reaction Explorer), we derive a restricted chemistry data set consisting of 1630 full multistep reactions with 2358 distinct starting materials and intermediates, associated with 2989 productive mechanistic steps and 6.14 million unproductive mechanistic steps. And from machine learning, we pose identifying productive mechanistic steps as a statistical ranking, information retrieval problem: given a set of reactants and a description of conditions, learn a ranking model over potential filled-to-unfilled MO interactions such that the top-ranked mechanistic steps yield the major products. The machine learning implementation follows a two-stage approach, in which we first train atom level reactivity filters to prune 94.00% of nonproductive reactions with a 0.01% error rate. Then, we train an ensemble of ranking models on pairs of interacting MOs to learn a relative productivity function over mechanistic steps in a given system. Without the use of explicit transformation patterns, the ensemble perfectly ranks the productive mechanism at the top 89.05% of the time, rising to 99.86% of the time when the top four are considered. Furthermore, the system

  3. Learning to Predict Chemical Reactions

    PubMed Central

    Kayala, Matthew A.; Azencott, Chloé-Agathe; Chen, Jonathan H.

    2011-01-01

    Being able to predict the course of arbitrary chemical reactions is essential to the theory and applications of organic chemistry. Approaches to the reaction prediction problems can be organized around three poles corresponding to: (1) physical laws; (2) rule-based expert systems; and (3) inductive machine learning. Previous approaches at these poles respectively are not high-throughput, are not generalizable or scalable, or lack sufficient data and structure to be implemented. We propose a new approach to reaction prediction utilizing elements from each pole. Using a physically inspired conceptualization, we describe single mechanistic reactions as interactions between coarse approximations of molecular orbitals (MOs) and use topological and physicochemical attributes as descriptors. Using an existing rule-based system (Reaction Explorer), we derive a restricted chemistry dataset consisting of 1630 full multi-step reactions with 2358 distinct starting materials and intermediates, associated with 2989 productive mechanistic steps and 6.14 million unproductive mechanistic steps. And from machine learning, we pose identifying productive mechanistic steps as a statistical ranking, information retrieval, problem: given a set of reactants and a description of conditions, learn a ranking model over potential filled-to-unfilled MO interactions such that the top ranked mechanistic steps yield the major products. The machine learning implementation follows a two-stage approach, in which we first train atom level reactivity filters to prune 94.00% of non-productive reactions with a 0.01% error rate. Then, we train an ensemble of ranking models on pairs of interacting MOs to learn a relative productivity function over mechanistic steps in a given system. Without the use of explicit transformation patterns, the ensemble perfectly ranks the productive mechanism at the top 89.05% of the time, rising to 99.86% of the time when the top four are considered. Furthermore, the system

  4. DESIGNING ENVIRONMENTALLY FRIENDLY CHEMICAL PROCESSES

    EPA Science Inventory

    The design of a chemical process involves many aspects: from profitability, flexibility and reliability to safety to the environment. While each of these is important, in this work, the focus will be on profitability and the environment. Key to the study of these aspects is the ...

  5. DESIGNING ENVIRONMENTALLY FRIENDLY CHEMICAL PROCESSES

    EPA Science Inventory

    The design of a chemical process involves many aspects: from profitability, flexibility and reliability to safety to the environment. While each of these is important, in this work, the focus will be on profitability and the environment. Key to the study of these aspects is the ...

  6. Environmental Chemicals and Nervous System Dysfunction 1

    PubMed Central

    Damstra, Terri

    1978-01-01

    Selected examples of associations between nervous system diseases and exposures to occupational and environmental chemicals have been reviewed. Recent outbreaks of human neurotoxicity from both wellknown and previously unknown toxicants reemphasize the need for the medical community to give increased attention to chemical causes of nervous system dysfunction. PMID:87062

  7. HUMAN HEALTH IMPACT OF ENVIRONMENTAL ESTROGENIC CHEMICALS

    EPA Science Inventory

    HUMAN HEALTH IMPACT OF ENVIRONMENTAL ESTROGENIC CHEMICALS.

    Robert J. Kavlock, Reproductive Toxicology Division, NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, NC USA.

    Over the past several decades a hypothesis has been put forth that a numb...

  8. HUMAN HEALTH IMPACT OF ENVIRONMENTAL ESTROGENIC CHEMICALS

    EPA Science Inventory

    HUMAN HEALTH IMPACT OF ENVIRONMENTAL ESTROGENIC CHEMICALS.

    Robert J. Kavlock, Reproductive Toxicology Division, NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, NC USA.

    Over the past several decades a hypothesis has been put forth that a numb...

  9. 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

  10. Prioritizing Environmental Chemicals for Obesity and Diabetes ...

    EPA Pesticide Factsheets

    Background: Diabetes and obesity are major threats to public health in the US and abroad. Understanding the role chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals for testing beyond those already implicated in the literature is a challenge. This review is intended to help researchers generate hypotheses about chemicals potentially contributing to diabetes and obesity-related health outcomes by summarizing relevant findings from the US Environmental Protection Agency (EPA) ToxCast high-throughput screening (HTS) program. Objectives: To develop new hypotheses around environmental chemicals of potential interest for diabetes- or obesity-related outcomes using high throughput screening data. Methods: Identify ToxCast assay targets relevant to several biological processes related to diabetes and obesity (insulin sensitivity in peripheral tissue, pancreatic islet and beta cell function, adipocyte dierentiation, and feeding behavior) and present chemical screening data against those assay targets to identify chemicals of potential interest. Discussion: Results of this screening-level analysis suggest that the spectrum of environmental chemicals to consider in research related to diabetes and obesity is much broader than indicated from research papers and reviews published in the peer-reviewed literature. Testing of hypotheses based on ToxCast data will a

  11. Environmental chemicals and microRNAs

    PubMed Central

    Hou, Lifang; Wang, Dong; Baccarelli, Andrea

    2013-01-01

    MicroRNAs (miRNAs) are short single-stranded non-coding molecules that function as negative regulators to silence or suppress gene expression. Aberrant miRNA expression has been implicated in a several cellular processes and pathogenic pathways of a number of diseases. Evidence is rapidly growing that miRNA regulation of gene expression may be affected by environmental chemicals. These environmental exposures include those that have frequently been associated with chronic diseases, such as heavy metals, air pollution, bisphenol A, and cigarette smoking. In this article, we review the published data on miRNAs in relation to the exposure to several environmental chemicals, and discuss the potential mechanisms that may link environmental chemicals to miRNA alterations. We further discuss the challenges in environmental-miRNA research and possible future directions. The cumulating evidence linking miRNAs to environmental chemicals, coupled with the unique regulatory role of miRNAs in gene expression, makes miRNAs potential biomarkers for better understanding the mechanisms of environmental diseases. PMID:21609724

  12. Predicting skin permeability from complex chemical mixtures

    SciTech Connect

    Riviere, Jim E. . E-mail: Jim_Riviere@ncsu.edu; Brooks, James D.

    2005-10-15

    Occupational and environmental exposure to topical chemicals is usually in the form of complex chemical mixtures, yet risk assessment is based on experimentally derived data from individual chemical exposures from a single, usually aqueous vehicle, or from computed physiochemical properties. We present an approach using hybrid quantitative structure permeation relationships (QSPeR) models where absorption through porcine skin flow-through diffusion cells is well predicted using a QSPeR model describing the individual penetrants, coupled with a mixture factor (MF) that accounts for physicochemical properties of the vehicle/mixture components. The baseline equation is log k {sub p} = c + mMF + a{sigma}{alpha} {sub 2} {sup H} + b{sigma}{beta} {sub 2} {sup H} + s{pi} {sub 2} {sup H} + rR {sub 2} + vV {sub x} where {sigma}{alpha} {sub 2} {sup H} is the hydrogen-bond donor acidity, {sigma}{beta} {sub 2} {sup H} is the hydrogen-bond acceptor basicity, {pi} {sub 2} {sup H} is the dipolarity/polarizability, R {sub 2} represents the excess molar refractivity, and V {sub x} is the McGowan volume of the penetrants of interest; c, m, a, b, s, r, and v are strength coefficients coupling these descriptors to skin permeability (k {sub p}) of 12 penetrants (atrazine, chlorpyrifos, ethylparathion, fenthion, methylparathion, nonylphenol, {rho}-nitrophenol, pentachlorophenol, phenol, propazine, simazine, and triazine) in 24 mixtures. Mixtures consisted of full factorial combinations of vehicles (water, ethanol, propylene glycol) and additives (sodium lauryl sulfate, methyl nicotinate). An additional set of 4 penetrants (DEET, SDS, permethrin, ricinoleic acid) in different mixtures were included to assess applicability of this approach. This resulted in a dataset of 16 compounds administered in 344 treatment combinations. Across all exposures with no MF, R{sup 2} for absorption was 0.62. With the MF, correlations increased up to 0.78. Parameters correlated to the MF include refractive

  13. Toxicokinetic Triage for Environmental Chemicals | Science ...

    EPA Pesticide Factsheets

    Toxicokinetic (TK) models are essential for linking administered doses to blood and tissue concentrations. In vitro-to-in vivo extrapolation (IVIVE) methods have been developed to determine TK from limited in vitro measurements and chemical structure-based property predictions, providing a less resource–intensive alternative to traditional in vivo TK approaches. High throughput TK (HTTK) methods use IVIVE to estimate doses that produce steady-state plasma concentrations equivalent to those producing biological activity in in vitro screening studies (e.g., ToxCast). In this study, the domain of applicability and assumptions of HTTK approaches were evaluated using both in vivo data and simulation analysis. Based on in vivo data for 87 chemicals, specific properties (e.g., in vitro HTTK data, physico-chemical descriptors, chemical structure, and predicted transporter affinities) were identified that correlate with poor HTTK predictive ability. For 350 xenobiotics with literature HTTK data, we then differentiated those xenobiotics for which HTTK approaches are likely to be sufficient, from those that may require additional data. For 272 chemicals we also developed a HT physiologically-based TK (HTPBTK) model that requires somewhat greater information than a steady-state model, but allows non-steady state dynamics and can predict chemical concentration time-courses for a variety of exposure scenarios, tissues, and species. We used this HTPBTK model to show that the

  14. Prediction of cancer drugs by chemical-chemical interactions.

    PubMed

    Lu, Jing; Huang, Guohua; Li, Hai-Peng; Feng, Kai-Yan; Chen, Lei; Zheng, Ming-Yue; Cai, Yu-Dong

    2014-01-01

    Cancer, which is a leading cause of death worldwide, places a big burden on health-care system. In this study, an order-prediction model was built to predict a series of cancer drug indications based on chemical-chemical interactions. According to the confidence scores of their interactions, the order from the most likely cancer to the least one was obtained for each query drug. The 1(st) order prediction accuracy of the training dataset was 55.93%, evaluated by Jackknife test, while it was 55.56% and 59.09% on a validation test dataset and an independent test dataset, respectively. The proposed method outperformed a popular method based on molecular descriptors. Moreover, it was verified that some drugs were effective to the 'wrong' predicted indications, indicating that some 'wrong' drug indications were actually correct indications. Encouraged by the promising results, the method may become a useful tool to the prediction of drugs indications.

  15. Characterization and Prediction of Chemical Functions and ...

    EPA Pesticide Factsheets

    Assessing exposures from the thousands of chemicals in commerce requires quantitative information on the chemical constituents of consumer products. Unfortunately, gaps in available composition data prevent assessment of exposure to chemicals in many products. Here we propose filling these gaps via consideration of chemical functional role. We obtained function information for thousands of chemicals from public sources and used a clustering algorithm to assign chemicals into 35 harmonized function categories (e.g., plasticizers, antimicrobials, solvents). We combined these functions with weight fraction data for 4115 personal care products (PCPs) to characterize the composition of 66 different product categories (e.g., shampoos). We analyzed the combined weight fraction/function dataset using machine learning techniques to develop quantitative structure property relationship (QSPR) classifier models for 22 functions and for weight fraction, based on chemical-specific descriptors (including chemical properties). We applied these classifier models to a library of 10196 data-poor chemicals. Our predictions of chemical function and composition will inform exposure-based screening of chemicals in PCPs for combination with hazard data in risk-based evaluation frameworks. As new information becomes available, this approach can be applied to other classes of products and the chemicals they contain in order to provide essential consumer product data for use in exposure-b

  16. Human Stem Cell Derived Cardiomyocytes: An Alternative Model to Evaluate Environmental Chemical Cardiac Safety and Development of Predictive Adverse Outcome Pathways

    EPA Science Inventory

    Chemical spills and associated deaths in the US has increased 2.6-fold and 16-fold from 1983 to 2012, respectfully. In addition, the number of chemicals to which humans are exposed to in the environment has increased almost 10-fold from 2001 to 2013 within the US. Internationally...

  17. Human Stem Cell Derived Cardiomyocytes: An Alternative Model to Evaluate Environmental Chemical Cardiac Safety and Development of Predictive Adverse Outcome Pathways

    EPA Science Inventory

    Chemical spills and associated deaths in the US has increased 2.6-fold and 16-fold from 1983 to 2012, respectfully. In addition, the number of chemicals to which humans are exposed to in the environment has increased almost 10-fold from 2001 to 2013 within the US. Internationally...

  18. Validated predictive modelling of the environmental resistome.

    PubMed

    Amos, Gregory C A; Gozzard, Emma; Carter, Charlotte E; Mead, Andrew; Bowes, Mike J; Hawkey, Peter M; Zhang, Lihong; Singer, Andrew C; Gaze, William H; Wellington, Elizabeth M H

    2015-06-01

    Multi-drug-resistant bacteria pose a significant threat to public health. The role of the environment in the overall rise in antibiotic-resistant infections and risk to humans is largely unknown. This study aimed to evaluate drivers of antibiotic-resistance levels across the River Thames catchment, model key biotic, spatial and chemical variables and produce predictive models for future risk assessment. Sediment samples from 13 sites across the River Thames basin were taken at four time points across 2011 and 2012. Samples were analysed for class 1 integron prevalence and enumeration of third-generation cephalosporin-resistant bacteria. Class 1 integron prevalence was validated as a molecular marker of antibiotic resistance; levels of resistance showed significant geospatial and temporal variation. The main explanatory variables of resistance levels at each sample site were the number, proximity, size and type of surrounding wastewater-treatment plants. Model 1 revealed treatment plants accounted for 49.5% of the variance in resistance levels. Other contributing factors were extent of different surrounding land cover types (for example, Neutral Grassland), temporal patterns and prior rainfall; when modelling all variables the resulting model (Model 2) could explain 82.9% of variations in resistance levels in the whole catchment. Chemical analyses correlated with key indicators of treatment plant effluent and a model (Model 3) was generated based on water quality parameters (contaminant and macro- and micro-nutrient levels). Model 2 was beta tested on independent sites and explained over 78% of the variation in integron prevalence showing a significant predictive ability. We believe all models in this study are highly useful tools for informing and prioritising mitigation strategies to reduce the environmental resistome.

  19. Validated predictive modelling of the environmental resistome

    PubMed Central

    Amos, Gregory CA; Gozzard, Emma; Carter, Charlotte E; Mead, Andrew; Bowes, Mike J; Hawkey, Peter M; Zhang, Lihong; Singer, Andrew C; Gaze, William H; Wellington, Elizabeth M H

    2015-01-01

    Multi-drug-resistant bacteria pose a significant threat to public health. The role of the environment in the overall rise in antibiotic-resistant infections and risk to humans is largely unknown. This study aimed to evaluate drivers of antibiotic-resistance levels across the River Thames catchment, model key biotic, spatial and chemical variables and produce predictive models for future risk assessment. Sediment samples from 13 sites across the River Thames basin were taken at four time points across 2011 and 2012. Samples were analysed for class 1 integron prevalence and enumeration of third-generation cephalosporin-resistant bacteria. Class 1 integron prevalence was validated as a molecular marker of antibiotic resistance; levels of resistance showed significant geospatial and temporal variation. The main explanatory variables of resistance levels at each sample site were the number, proximity, size and type of surrounding wastewater-treatment plants. Model 1 revealed treatment plants accounted for 49.5% of the variance in resistance levels. Other contributing factors were extent of different surrounding land cover types (for example, Neutral Grassland), temporal patterns and prior rainfall; when modelling all variables the resulting model (Model 2) could explain 82.9% of variations in resistance levels in the whole catchment. Chemical analyses correlated with key indicators of treatment plant effluent and a model (Model 3) was generated based on water quality parameters (contaminant and macro- and micro-nutrient levels). Model 2 was beta tested on independent sites and explained over 78% of the variation in integron prevalence showing a significant predictive ability. We believe all models in this study are highly useful tools for informing and prioritising mitigation strategies to reduce the environmental resistome. PMID:25679532

  20. The chemical and environmental property space of REACH chemicals.

    PubMed

    Öberg, Tomas; Iqbal, M Sarfraz

    2012-05-01

    The European regulation on chemicals, REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals), came into force on 1 June 2007. With pre-registration complete in 2008, data for these substances may provide an overview of the expected chemical space and its characteristics. In this paper, using various in silico computation tools, we evaluate 48782 neutral organic compounds from the list to identify hazardous and safe compounds. Two different classification schemes (modified Verhaar and ECOSAR) identified between 17% and 25% of the compounds as expressing only baseline toxicity (narcosis). A smaller portion could be identified as reactive (19%) or specifically acting (2.7%), while the majority were non-assigned (61%). Overall environmental persistence, bioaccumulation and long-range transport potential were evaluated using structure-activity relationships and a multimedia fugacity-based model. A surprisingly high proportion of compounds (20%), mainly aromatic and halogenated, had a very high estimated persistence (>195 d). The proportion of compounds with a very high estimated bioconcentration or bioaccumulation factor (>5000) was substantially less (6.9%). Finally, a list was compiled of those compounds within the applicability domain of the models used, meeting both persistence and bioaccumulation criteria, and with a long-range transport potential comparable to PCB. This list of 68 potential persistent organic pollutants contained many well-known compounds (all halogenated), but notably also five fluorinated compounds that were not included in the EINECS inventory. This study demonstrates the usability of in silico tools for identification of potentially environmentally hazardous chemicals.

  1. High throughput heuristics for prioritizing human exposure to environmental chemicals.

    PubMed

    Wambaugh, John F; Wang, Anran; Dionisio, Kathie L; Frame, Alicia; Egeghy, Peter; Judson, Richard; Setzer, R Woodrow

    2014-11-04

    The risk posed to human health by any of the thousands of untested anthropogenic chemicals in our environment is a function of both the hazard presented by the chemical and the extent of exposure. However, many chemicals lack estimates of exposure intake, limiting the understanding of health risks. We aim to develop a rapid heuristic method to determine potential human exposure to chemicals for application to the thousands of chemicals with little or no exposure data. We used Bayesian methodology to infer ranges of exposure consistent with biomarkers identified in urine samples from the U.S. population by the National Health and Nutrition Examination Survey (NHANES). We performed linear regression on inferred exposure for demographic subsets of NHANES demarked by age, gender, and weight using chemical descriptors and use information from multiple databases and structure-based calculators. Five descriptors are capable of explaining roughly 50% of the variability in geometric means across 106 NHANES chemicals for all the demographic groups, including children aged 6-11. We use these descriptors to estimate human exposure to 7968 chemicals, the majority of which have no other quantitative exposure prediction. For thousands of chemicals with no other information, this approach allows forecasting of average exposure intake of environmental chemicals.

  2. Priority Environmental Chemical Contaminants in Meat

    NASA Astrophysics Data System (ADS)

    Brambilla, Gianfranco; Iamiceli, Annalaura; di Domenico, Alessandro

    Generally, foods of animal origin play an important role in determining the exposure of human beings to contaminants of both biological and chemical origins (Ropkins & Beck, 2002; Lievaart et al., 2005). A potentially large number of chemicals could be considered, several of them deserving a particular attention due to their occurrence (contaminations levels and frequencies) and intake scenarios reflecting the differences existing in the economical, environmental, social and ecological contexts in which the “from-farm-to-fork” activities related to meat production are carried out (FAO - Food and Agriculture Organization, 2008).

  3. Health and environmental effects of complex chemical mixtures: proceedings

    SciTech Connect

    Not Available

    1985-01-01

    The Office of Health and Environmental Research (OHER) of the Department of Energy supports a broad long-term research program on human health and environmental effects from potential exposure to energy-related complex chemical mixtures. The program seeks basic mechanistic data on the effects of complex mixtures at the cellular, molecular, and whole animal levels to aid in predicting human health effects and seeks ecological data on biological and physical transformations in the mixtures, concentrations of the mixtures in various compartments of the environment, and potential routes for human exposure to these mixtures (e.g., food chain). On June 17-18, 1985, OHER held its First Annual Technical Meeting on the Complex Chemical Mixtures Program in Chicago, IL. The primary purpose of the meeting was to enable principal investigators to report the research status and accomplishments of ongoing complex chemical mixture studies supported by OHER. To help focus future research directions round table discussions were conducted.

  4. Jensen's Inequality Predicts Effects of Environmental Variation

    Treesearch

    Jonathan J. Ruel; Matthew P. Ayres

    1999-01-01

    Many biologists now recognize that environmental variance can exert important effects on patterns and processes in nature that are independent of average conditions. Jenson's inequality is a mathematical proof that is seldom mentioned in the ecological literature but which provides a powerful tool for predicting some direct effects of environmental variance in...

  5. Global Environmental Multiscale model - a platform for integrated environmental predictions

    NASA Astrophysics Data System (ADS)

    Kaminski, Jacek W.; Struzewska, Joanna; Neary, Lori; Dearden, Frank

    2017-04-01

    The Global Environmental Multiscale model was developed by the Government of Canada as an operational weather prediction model in the mid-1990s. Subsequently, it was used as the host meteorological model for an on-line implementation of air quality chemistry and aerosols from global to the meso-gamma scale. Further model developments led to the vertical extension of the modelling domain to include stratospheric chemistry, aerosols, and formation of polar stratospheric clouds. In parallel, the modelling platform was used for planetary applications where dynamical, radiative transfer and chemical processes in the atmosphere of Mars were successfully simulated. Undoubtedly, the developed modelling platform can be classified as an example capable of the seamless and coupled modelling of the dynamics and chemistry of planetary atmospheres. We will present modelling results for global, regional, and local air quality episodes and the long-term air quality trends. Upper troposphere and lower stratosphere modelling results will be presented in terms of climate change and subsonic aviation emissions modelling. Model results for the atmosphere of Mars will be presented in the context of the 2016 ExoMars mission and the anticipated observations from the NOMAD instrument. Also, we will present plans and the design to extend the GEM model to the F region with further coupling with a magnetospheric model that extends to 15 Re.

  6. Environmental mimics of chemical warfare agents.

    PubMed

    Claborn, David M

    2004-12-01

    There are several natural and artificial factors that mimic the effects of chemical warfare agents, thereby causing unwarranted alarm and confusion on the battlefield. Symptoms associated with chemical warfare include paralysis, muscle tremors, heavy salivation, severe burns, blistering, and corrosive skin injuries among others. Similar symptoms can be produced from a variety of environmental sources, artificial and natural. This article reviews several published and unpublished examples of environmental factors that produce syndromes similar to those caused by these agents. Examples of such mimics include pesticides, blistering exudates from insects and plants, various types of bites, and naturally occurring diseases. The potential for confusion caused by these factors is discussed and means of discriminating between warfare agents and naturally occurring events are identified. Recommendations for the use of this information and for needed research are also discussed.

  7. Allergic contact sensitizing chemicals as environmental carcinogens.

    PubMed Central

    Albert, R E

    1997-01-01

    Chemicals that were bioassayed by the National Toxicology Program (NTP) and that also produce allergic dermatitis (ACD) in humans were evaluated for their tumorigenic characteristics. The impetus for the study was that most contact sensitizers, i.e., those that produce ACD, and genotoxic carcinogens are chemically similar in that they are electrophilic, thereby producing adducts on macromolecules including protein and DNA. This similarity in chemical behavior suggests that many contact sensitizers might be environmental carcinogens. All of the published NTP bioassays by early 1996 that had both genotoxicity and carcinogenicity studies were included in this analysis. The NTP chemicals had been chosen for bioassay without regard to their ability to produce ACD. Of the 209 chemicals that were bioassayed, there were 36 (17%) that were known to be human contact sensitizers; about half of these were positive on tumor bioassays. The contact sensitizers differed from the NTP sample as a whole by having a proportionately larger number of nongenotoxic chemicals by the Ames Salmonella assay, presumably because more of them were selected on the basis of widespread usage rather than structural resemblance to known carcinogens. Compared to the nongenotoxic chemicals, the genotoxics were stronger carcinogens in that they had a higher incidence of positive tumor bioassays, with twice the number of organs in which tumors were induced. The nongenotoxic chemicals had a preference for tumor induction in parenchymal tissues in contrast to epithelial tissues. The contact sensitizers showed essentially the same characteristics as the whole NTP sample when stratified according to genotoxicity. Judging by the chemicals that were chosen primarily for their widespread use rather than for their structural resemblance to carcinogens, the addition of a test for contact sensitization to the Ames test as a screening tool would increase the tumorigenic detection efficiency by about 40% because of

  8. Alterations in macrophage functions by environmental chemicals.

    PubMed Central

    Gardner, D E

    1984-01-01

    The establishment of infectious diseases is rarely entirely attributed to a single entity, but instead is the result of a primary stress and one or more secondary factors that interfere with homeostasis and the ability of the host to cope with the primary etiologic assault. Any environmental chemical that can suppress the normal functioning of the host's body defenses would be expected to increase the risk of the host to such diseases. Within the lung, the alveolar macrophages are the crucial elements responsible for defending the body against such airborne viable agents. The effects of inhaled gases and particulates on these defense cells are a major concern of the environmental health scientist since such chemicals have the capability of adversely affecting the integrity and functioning of these pulmonary defense cells. The objective of this report is to provide an overview that will improve our understanding of how a variety of environmental chemicals can alter the biochemical, physiological and immunological functioning of these cells. PMID:6376106

  9. Multiple Classes of Environmental Chemicals are Associated ...

    EPA Pesticide Factsheets

    Biomonitoring of human tissues and fluids has shown that virtually all individuals, worldwide, carry a “body burden” of synthetic chemicals (Thornton et al. 2002; CDC 2009). Although the measurement of an environmental chemical in a person’s tissues or fluids is an indication of exposure, it does not by itself mean that the chemical or the exposure concentration is sufficient to cause a disease or an adverse effect. However, since humans are exposed to multiple chemicals, there may be a combination effect (e.g., additive, synergistic) on health risks associated with exposure even at low levels (Kortenkamp 2008). Further, biomonitoring studies show that humans carry a body burden of multiple classes of contaminants which are often not studied together. We used the 2003-2006 National Health and Nutrition Examination Survey to evaluate the relationship between alanine aminotransferase (ALT) and 53 environmental contaminants across six classes (metals; perfluorinated compounds [PFCs]; phthalates; phenols; coplanar and non-dioxin-like polychlorinated biphenyls [PCBs]) using a novel method.

  10. Environmental chemistry of chemical warfare agents

    SciTech Connect

    MacNaughton, M.G.; Brewer, J.H.; Ledbetter-Ferrill, J.

    1995-06-01

    This paper summarizes the approach used in the preparation of a Handbook for the Corps of Engineers, Huntsville Division, on the environmental chemistry of chemical warfare agents. The agents GB and HD will be used to illustrate the type of information in the report. Those readers interested in the full report should contact Mr. Arkie Fanning, Huntsville Corps of Engineers at (505) 955-5256. The U.S. Army Corps of Engineers (ACE) has identified approximately 7,200 formerly used defense sites (FUDS) in the United States, some of which are suspected to be contaminated with chemical warfare agents (CWA). The ACE has responsibility for environmental clean-up of FUDS, including site characterization, evaluation and remediation of the site. Thirty-four FUDS and 48 active DOD installations that may contain CWA were identified in an Interim Survey and Analysis Report by the USACMDA Program Manager for Non-Stockpile Chemical Material (NSCM). The chemical agents listed include sulfur mustard (H), lewisite (L), tabun (GA), sarin (GB), VX, hydrogen cyanide (AC), cyanogen chloride (CK), phosgene (CG), BZ, and CS.

  11. ToxCast: Developing Predictive Signatures of Chemically Induced Toxicity (Developing Predictive Bioactivity Signatures from ToxCasts HTS Data)

    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...

  12. ToxCast: Developing Predictive Signatures of Chemically Induced Toxicity (Developing Predictive Bioactivity Signatures from ToxCasts HTS Data)

    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...

  13. Positive genetic hazard predictions from short-term tests have proved false for results in mammalian spermatogonia with all environmental chemicals so far tested

    SciTech Connect

    Russell, W.L.

    1985-01-01

    Eleven chemicals for which there has been considerable human exposure were studied by the mouse specific-locus method because of their positive mutagenic action in other test systems. All were positive in the Drosophila sex-linked recessive lethal test, and in mammalian somatic cells proved mutagenic. In mouse stem-cell spermatogonia none of the chemicals, even at maximum tolerated dose, has given a specific-locus mutation frequency higher than the control, and the mutation frequency for all eleven combined (12 mutations in 298,502 offspring) was actually less than the historical control. Absence of mutation induction cannot be attributed to: (a) failure of the chemicals to reach the testis (10 of them are known to reach the testis in active form), (b) small sample size (the samples are large), (c) insensitivity of the test (the test is not insensitive: a positive control gave a mutation frequency 132 times higher than the historical control). It is concluded that mammalian stem-cell spermatogonia have an effective repair capability. 9 refs., 1 tab.

  14. Prediction of Cancer Drugs by Chemical-Chemical Interactions

    PubMed Central

    Li, Hai-Peng; Feng, Kai-Yan; Chen, Lei; Zheng, Ming-Yue; Cai, Yu-Dong

    2014-01-01

    Cancer, which is a leading cause of death worldwide, places a big burden on health-care system. In this study, an order-prediction model was built to predict a series of cancer drug indications based on chemical-chemical interactions. According to the confidence scores of their interactions, the order from the most likely cancer to the least one was obtained for each query drug. The 1st order prediction accuracy of the training dataset was 55.93%, evaluated by Jackknife test, while it was 55.56% and 59.09% on a validation test dataset and an independent test dataset, respectively. The proposed method outperformed a popular method based on molecular descriptors. Moreover, it was verified that some drugs were effective to the ‘wrong’ predicted indications, indicating that some ‘wrong’ drug indications were actually correct indications. Encouraged by the promising results, the method may become a useful tool to the prediction of drugs indications. PMID:24498372

  15. Influences of Environmental Chemicals on Atopic Dermatitis

    PubMed Central

    2015-01-01

    Atopic dermatitis is a chronic inflammatory skin condition including severe pruritus, xerosis, visible eczematous skin lesions that mainly begin early in life. Atopic dermatitis exerts a profound impact on the quality of life of patients and their families. The estimated lifetime prevalence of atopic dermatitis has increased 2~3 fold during over the past 30 years, especially in urban areas in industrialized countries, emphasizing the importance of life-style and environment in the pathogenesis of atopic diseases. While the interplay of individual genetic predisposition and environmental factors contribute to the development of atopic dermatitis, the recent increase in the prevalence of atopic dermatitis might be attributed to increased exposure to various environmental factors rather than alterations in human genome. In recent decades, there has been an increasing exposure to chemicals from a variety of sources. In this study, the effects of various environmental chemicals we face in everyday life - air pollutants, contact allergens and skin irritants, ingredients in cosmetics and personal care products, and food additives - on the prevalence and severity of atopic dermatitis are reviewed. PMID:26191377

  16. Predicting chemical impacts on vertebrate endocrine systems.

    PubMed

    Nichols, John W; Breen, Miyuki; Denver, Robert J; Distefano, Joseph J; Edwards, Jeremy S; Hoke, Robert A; Volz, David C; Zhang, Xiaowei

    2011-01-01

    Animals have evolved diverse protective mechanisms for responding to toxic chemicals of both natural and anthropogenic origin. From a governmental regulatory perspective, these protective responses complicate efforts to establish acceptable levels of chemical exposure. To explore this issue, we considered vertebrate endocrine systems as potential targets for environmental contaminants. Using the hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-gonad (HPG), and hypothalamic-pituitary-adrenal (HPA) axes as case examples, we identified features of these systems that allow them to accommodate and recover from chemical insults. In doing so, a distinction was made between effects on adults and those on developing organisms. This distinction was required because endocrine system disruption in early life stages may alter development of organs and organ systems, resulting in permanent changes in phenotypic expression later in life. Risk assessments of chemicals that impact highly regulated systems must consider the dynamics of these systems in relation to complex environmental exposures. A largely unanswered question is whether successful accommodation to a toxic insult exerts a fitness cost on individual animals, resulting in adverse consequences for populations. Mechanistically based mathematical models of endocrine systems provide a means for better understanding accommodation and recovery. In the short term, these models can be used to design experiments and interpret study findings. Over the long term, a set of validated models could be used to extrapolate limited in vitro and in vivo testing data to a broader range of untested chemicals, species, and exposure scenarios. With appropriate modification, Tier 2 assays developed in support of the U.S. Environmental Protection Agency's Endocrine Disruptor Screening Program could be used to assess the potential for accommodation and recovery and inform the development of mechanistically based models.

  17. Predicting the bioconcentration factor of highly hydrophobic organic chemicals.

    PubMed

    Garg, Rajni; Smith, Carr J

    2014-07-01

    Bioconcentration refers to the process of uptake and buildup of chemicals in living organisms. Experimental measurement of bioconcentration factor (BCF) is time-consuming and expensive, and is not feasible for a large number of chemicals of regulatory concern. Quantitative structure-activity relationship (QSAR) models are used for estimating BCF values to help in risk assessment of a chemical. This paper presents the results of a QSAR study conducted to address an important problem encountered in the prediction of the BCF of highly hydrophobic chemicals. A new QSAR model is derived using a dataset of diverse organic chemicals previously tested in a United States Environmental Protection Agency laboratory. It is noted that the linear relationship between the BCF and hydrophobic parameter, i.e., calculated octanol-water partition coefficient (ClogP), breaks down for highly hydrophobic chemicals. The parabolic QSAR equation, log BCF=3.036 ClogP-0.197 ClogP(2)-0.808 MgVol (n=28, r(2)=0.817, q(2)=0.761, s=0.558) (experimental log BCF range=0.44-5.29, ClogP range=3.16-11.27), suggests that a non-linear relationship between BCF and the hydrophobic parameter, along with inclusion of additional molecular size, weight and/or volume parameters, should be considered while developing a QSAR model for more reliable prediction of the BCF of highly hydrophobic chemicals.

  18. Use of the Chemical Transformation Simulator as a Parameterization Tool for Modeling the Environmental Fate of Organic Chemicals and their Transformation Products

    EPA Science Inventory

    A Chemical Transformation Simulator is a web-based system for predicting transformation pathways and physicochemical properties of organic chemicals. Role in Environmental Modeling • Screening tool for identifying likely transformation products in the environment • Parameteri...

  19. Use of the Chemical Transformation Simulator as a Parameterization Tool for Modeling the Environmental Fate of Organic Chemicals and their Transformation Products

    EPA Science Inventory

    A Chemical Transformation Simulator is a web-based system for predicting transformation pathways and physicochemical properties of organic chemicals. Role in Environmental Modeling • Screening tool for identifying likely transformation products in the environment • Parameteri...

  20. Chemical Shift Prediction for Denatured Proteins

    PubMed Central

    Sahu, Sarata C.; Nkari, Wendy K.; Morris, Laura C.; Live, David; Gruta, Christian

    2013-01-01

    While chemical shift prediction has played an important role in aspects of protein NMR that include identification of secondary structure, generation of torsion angle constraints for structure determination, and assignment of resonances in spectra of intrinsically disordered proteins, interest has arisen more recently in using it in alternate assignment strategies for crosspeaks in 1H-15N HSQC spectra of sparsely labeled proteins. One such approach involves correlation of crosspeaks in the spectrum of the native protein with those observed in the spectrum of the denatured protein, followed by assignment of the peaks in the latter spectrum. As in the case of disordered proteins, predicted chemical shifts can aid in these assignments. Some previously developed empirical formulas for chemical shift prediction have depended on basis data sets of 20 pentapeptides. In each case the central residue was varied among the 20 amino common acids, with the flanking residues held constant throughout the given series. However, previous choices of solvent conditions and flanking residues make the parameters in these formulas less than ideal for general application to denatured proteins. Here, we report 1H and 15N shifts for a set of alanine based pentapeptides under the low pH urea denaturing conditions that are more appropriate for sparse label assignments. New parameters have been derived and a Perl script was created to facilitate comparison with other parameter sets. A small, but significant, improvement in shift predictions for denatured ubiquitin is demonstrated. PMID:23297019

  1. Chemical shift prediction for denatured proteins.

    PubMed

    Prestegard, James H; Sahu, Sarata C; Nkari, Wendy K; Morris, Laura C; Live, David; Gruta, Christian

    2013-02-01

    While chemical shift prediction has played an important role in aspects of protein NMR that include identification of secondary structure, generation of torsion angle constraints for structure determination, and assignment of resonances in spectra of intrinsically disordered proteins, interest has arisen more recently in using it in alternate assignment strategies for crosspeaks in (1)H-(15)N HSQC spectra of sparsely labeled proteins. One such approach involves correlation of crosspeaks in the spectrum of the native protein with those observed in the spectrum of the denatured protein, followed by assignment of the peaks in the latter spectrum. As in the case of disordered proteins, predicted chemical shifts can aid in these assignments. Some previously developed empirical formulas for chemical shift prediction have depended on basis data sets of 20 pentapeptides. In each case the central residue was varied among the 20 amino common acids, with the flanking residues held constant throughout the given series. However, previous choices of solvent conditions and flanking residues make the parameters in these formulas less than ideal for general application to denatured proteins. Here, we report (1)H and (15)N shifts for a set of alanine based pentapeptides under the low pH urea denaturing conditions that are more appropriate for sparse label assignments. New parameters have been derived and a Perl script was created to facilitate comparison with other parameter sets. A small, but significant, improvement in shift predictions for denatured ubiquitin is demonstrated.

  2. Sea-dumped chemical weapons: environmental risk, occupational hazard.

    PubMed

    Greenberg, M I; Sexton, K J; Vearrier, D

    2016-01-01

    Chemical weapons dumped into the ocean for disposal in the twentieth century pose a continuing environmental and human health risk. In this review we discuss locations, quantity, and types of sea-dumped chemical weapons, related environmental concerns, and human encounters with sea-dumped chemical weapons. We utilized the Ovid (http://ovidsp.tx.ovid.com) and PubMed (http://www.pubmed.org) search engines to perform MEDLINE searches for the terms 'sea-dumped chemical weapons', 'chemical warfare agents', and 'chemical munitions'. The searches returned 5863 articles. Irrelevant and non-English articles were excluded. A review of the references for these articles yielded additional relevant sources, with a total of 64 peer-reviewed articles cited in this paper. History and geography of chemical weapons dumping at sea: Hundreds of thousands of tons of chemical munitions were disposed off at sea following World War II. European, Russian, Japanese, and United States coasts are the areas most affected worldwide. Several areas in the Baltic and North Seas suffered concentrated large levels of dumping, and these appear to be the world's most studied chemical warfare agent marine dumping areas. Chemical warfare agents: Sulfur mustard, Lewisite, and the nerve agents appear to be the chemical warfare agents most frequently disposed off at sea. Multiple other type of agents including organoarsenicals, blood agents, choking agents, and lacrimators were dumped at sea, although in lesser volumes. Environmental concerns: Numerous geohydrologic variables contribute to the rate of release of chemical agents from their original casings, leading to difficult and inexact modeling of risk of release into seawater. Sulfur mustard and the organoarsenicals are the most environmentally persistent dumped chemical agents. Sulfur mustard in particular has a propensity to form a solid or semi-solid lump with a polymer coating of breakdown products, and can persist in this state on the ocean floor

  3. Network predicting drug's anatomical therapeutic chemical code.

    PubMed

    Wang, Yong-Cui; Chen, Shi-Long; Deng, Nai-Yang; Wang, Yong

    2013-05-15

    Discovering drug's Anatomical Therapeutic Chemical (ATC) classification rules at molecular level is of vital importance to understand a vast majority of drugs action. However, few studies attempt to annotate drug's potential ATC-codes by computational approaches. Here, we introduce drug-target network to computationally predict drug's ATC-codes and propose a novel method named NetPredATC. Starting from the assumption that drugs with similar chemical structures or target proteins share common ATC-codes, our method, NetPredATC, aims to assign drug's potential ATC-codes by integrating chemical structures and target proteins. Specifically, we first construct a gold-standard positive dataset from drugs' ATC-code annotation databases. Then we characterize ATC-code and drug by their similarity profiles and define kernel function to correlate them. Finally, we use a kernel method, support vector machine, to automatically predict drug's ATC-codes. Our method was validated on four drug datasets with various target proteins, including enzymes, ion channels, G-protein couple receptors and nuclear receptors. We found that both drug's chemical structure and target protein are predictive, and target protein information has better accuracy. Further integrating these two data sources revealed more experimentally validated ATC-codes for drugs. We extensively compared our NetPredATC with SuperPred, which is a chemical similarity-only based method. Experimental results showed that our NetPredATC outperforms SuperPred not only in predictive coverage but also in accuracy. In addition, database search and functional annotation analysis support that our novel predictions are worthy of future experimental validation. In conclusion, our new method, NetPredATC, can predict drug's ATC-codes more accurately by incorporating drug-target network and integrating data, which will promote drug mechanism understanding and drug repositioning and discovery. NetPredATC is available at http

  4. ToxCast: Developing Predictive Signatures of Chemically ...

    EPA Pesticide Factsheets

    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 resources (www.epa.gov/tocast). In the proof-of-concept phase, we are focused upon evaluating chemicals with an existing, rich toxicological database in order to provide an interpretive context for the high through put screening data. This set of 320 reference chemicals are largely derived from the active ingredients in food use pesticides and represent numerous structural classes and phenotypic outcomes, including tumorigens, developmental and reproductive toxicants, neurotoxicants and irnrnunotoxicants. The goal of the program is to develop signatures based on the combined use of physico-chemical properties (the traditional independent variables in structure activity models) and the bioactivity data (derived from a broad spectrum of more than 400 readouts from biochemical assays, cell-based phenotypic assays, and genomic analyses of cells) that are predictive of responses in animal bioassays. The signatures derived for chemicals with toxicity data gaps could then be compared with those of the well characterized chemicals, and those with significant signatures would become priority candidates for testing in traditional animal bioassays. These data are being generated through a series of

  5. INTERSPECIES CORRELATION ESTIMATES PREDICT PROTECTIVE ENVIRONMENTAL CONCENTRATIONS

    EPA Science Inventory

    Environmental risk assessments often use multiple single species toxicity test results and species sensitivity distributions (SSDs) to derive a predicted no-effect concentration in the environment, typically the 5th percentile of the SSD, termed the HC5. The shape and location of...

  6. INTERSPECIES CORRELATION ESTIMATES PREDICT PROTECTIVE ENVIRONMENTAL CONCENTRATIONS

    EPA Science Inventory

    Environmental risk assessments often use multiple single species toxicity test results and species sensitivity distributions (SSDs) to derive a predicted no-effect concentration in the environment, typically the 5th percentile of the SSD, termed the HC5. The shape and location of...

  7. Predicting hepatotoxicity using ToxCast in vitro bioactivity and chemical structure

    EPA Science Inventory

    Background: The U.S. EPA ToxCastTM program is screening thousands of environmental chemicals for bioactivity using hundreds of high-throughput in vitro assays to build predictive models of toxicity. We represented chemicals based on bioactivity and chemical structure descriptors ...

  8. Predicting hepatotoxicity using ToxCast in vitro bioactivity and chemical structure

    EPA Science Inventory

    Background: The U.S. EPA ToxCastTM program is screening thousands of environmental chemicals for bioactivity using hundreds of high-throughput in vitro assays to build predictive models of toxicity. We represented chemicals based on bioactivity and chemical structure descriptors ...

  9. Environmental remediation monitoring using chemical sensors

    SciTech Connect

    Dong X. Li

    1996-12-31

    Monitoring is one of the most critical steps in environmental site remediation. However, the conventional technique of monitoring {open_quotes}inlet{close_quotes} and {open_quotes}outlet{close_quotes} of a process stream is no longer applicable in many in-situ remedial processes such as bioventing, biosparging, and intrinsic bioremediation. Traditional soil sampling and analysis is also unsuitable for monitoring biodegradation process because of chemical and biological inhomogeneity in soil. Soil gas measurement, on the other hand, is one of the few techniques available which is ideally suited for monitoring in-situ processes, since bioremediation processes involve gaseous components such as oxygen and carbon dioxide. In addition to oxygen and carbon dioxide, contaminant vapors and other trace gaseous components found in the pores of unsaturated soils also provide information on the spatial distribution and the extent of biodegradation. These gaseous components are very mobile, which are ideal analytes for chemical sensors. In this study, oxygen, carbon dioxide, and hydrocarbon subsurface chemical sensors were employed for monitoring in-situ bioremediation of petroleum hydrocarbon contaminated soils.

  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. 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...

  12. Environmental effects of oilfield chemicals on composite

    SciTech Connect

    Sorem, R.M.

    1998-12-31

    This paper presents a feasibility study of the effects of oilfield chemicals on composite materials. In this initial study only hydrochloric acid is considered. Initial attempts were made to test stressed specimens, but results were very poor. Subsequent testing was performed to determine how the composite material constituents reacted to the hydrochloric acid. The initial testing was performed on tubular specimens with axial and essentially hoop wound fibers of different materials with different resins. The specimens were loaded in bending to induce representative strains in the tubing. All specimens failed. The second tests consisted of only an environmental soak to determine the amount of mass uptake as well as the reduction in strength. The strength reduction results will be presented at a later time. Testing was performed on S-2 glass, carbon and Kevlar 49 as well as three different resins.

  13. Systematic chemical-genetic and chemical-chemical interaction datasets for prediction of compound synergism.

    PubMed

    Wildenhain, Jan; Spitzer, Michaela; Dolma, Sonam; Jarvik, Nick; White, Rachel; Roy, Marcia; Griffiths, Emma; Bellows, David S; Wright, Gerard D; Tyers, Mike

    2016-11-22

    The network structure of biological systems suggests that effective therapeutic intervention may require combinations of agents that act synergistically. However, a dearth of systematic chemical combination datasets have limited the development of predictive algorithms for chemical synergism. Here, we report two large datasets of linked chemical-genetic and chemical-chemical interactions in the budding yeast Saccharomyces cerevisiae. We screened 5,518 unique compounds against 242 diverse yeast gene deletion strains to generate an extended chemical-genetic matrix (CGM) of 492,126 chemical-gene interaction measurements. This CGM dataset contained 1,434 genotype-specific inhibitors, termed cryptagens. We selected 128 structurally diverse cryptagens and tested all pairwise combinations to generate a benchmark dataset of 8,128 pairwise chemical-chemical interaction tests for synergy prediction, termed the cryptagen matrix (CM). An accompanying database resource called ChemGRID was developed to enable analysis, visualisation and downloads of all data. The CGM and CM datasets will facilitate the benchmarking of computational approaches for synergy prediction, as well as chemical structure-activity relationship models for anti-fungal drug discovery.

  14. Systematic chemical-genetic and chemical-chemical interaction datasets for prediction of compound synergism

    PubMed Central

    Wildenhain, Jan; Spitzer, Michaela; Dolma, Sonam; Jarvik, Nick; White, Rachel; Roy, Marcia; Griffiths, Emma; Bellows, David S.; Wright, Gerard D.; Tyers, Mike

    2016-01-01

    The network structure of biological systems suggests that effective therapeutic intervention may require combinations of agents that act synergistically. However, a dearth of systematic chemical combination datasets have limited the development of predictive algorithms for chemical synergism. Here, we report two large datasets of linked chemical-genetic and chemical-chemical interactions in the budding yeast Saccharomyces cerevisiae. We screened 5,518 unique compounds against 242 diverse yeast gene deletion strains to generate an extended chemical-genetic matrix (CGM) of 492,126 chemical-gene interaction measurements. This CGM dataset contained 1,434 genotype-specific inhibitors, termed cryptagens. We selected 128 structurally diverse cryptagens and tested all pairwise combinations to generate a benchmark dataset of 8,128 pairwise chemical-chemical interaction tests for synergy prediction, termed the cryptagen matrix (CM). An accompanying database resource called ChemGRID was developed to enable analysis, visualisation and downloads of all data. The CGM and CM datasets will facilitate the benchmarking of computational approaches for synergy prediction, as well as chemical structure-activity relationship models for anti-fungal drug discovery. PMID:27874849

  15. Robotic automation of the environmental chemical laboratory

    SciTech Connect

    Hollen, R.M.; Erkkila, T.H.

    1994-04-01

    To date, automation of the environmental chemical laboratory has been a slow and tedious affair. In many, of our domestic analytical laboratories, automation consists of no more than analytical instrumentation coupled to an autosampling device. When we look into the future environmental needs of our nation, and indeed the world, it is apparent that we will not be able to keep up with the drastically increasing sample load without automated analyses. Stricter regulatory requirements on the horizon will potentially mandate staggering changes in sampling and characterization requirements. The Contaminant Analysis Automation (CAA) Program was initiated in 1990 by the US government`s Department of Energy (DOE) to address these issues. By application of a new robotics paradigm, based on an integrated production chemistry foundation applied to analytical chemistry, the CAA will use standardized modular instruments called Standard Laboratory Modules (SLM) to provide flexible and standardized automation systems. By promoting the commercialization of this technology, CAA will provide the integrated robotics systems necessary to meet the coming remediation demands. This multilaboratory program is within the Robotics Technology Development Program (RTDP) of the Office of Technology Development (OTD).

  16. Analytic considerations for measuring environmental chemicals in breast milk.

    PubMed Central

    Needham, Larry L; Wang, Richard Y

    2002-01-01

    The presence of environmental chemicals in human breast milk is of general concern because of the potential health consequence of these chemicals to the breast-fed infant and the mother. In addition to the mother's exposure, several features determine the presence of environmental chemicals in breast milk and their ability to be determined analytically. These include maternal factors and properties of the environmental chemical--both physical and chemical--such as its lipid solubility, degree of ionization, and molecular weight. Environmental chemicals with high lipid solubility are likely to be found in breast milk; they include polyhalogenated compounds such as polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, organochlorine insecticides, and polybrominated diphenylethers. These fat-soluble chemicals are incorporated into the milk as it is synthesized, and they must be measured in accordance with the fat content of the milk to allow for meaningful comparisons within an individual and among populations. Although the analytic approach selected to measure the environmental chemical is predominantly determined by the characteristics of the chemical, the concentration of the chemical in the milk sample and the existence of structurally similar chemicals (e.g., congeners) must be considered as well. In general, the analytic approach for measuring environmental chemicals in breast milk is similar to the approach for measuring the same chemicals in other matrices, except special considerations must be given for the relatively high fat content of milk. The continued efforts of environmental scientists to measure environmental chemicals in breast milk is important for defining the true contribution of these chemicals to public health, especially to the health of the newborn. Work is needed for identifying and quantifying additional environmental chemicals in breast milk from the general population and for developing analytic

  17. DESIGNING ENVIRONMENTALLY FRIENDLY CHEMICAL PROCESSES WITH FUGITIVE AND OPEN EMISSIONS

    EPA Science Inventory

    Designing a chemical process normally includes aspects of economic and environmental disciplines. In this work we describe methods to quickly and easily evaluate the economics and potential environmental impacts of a process, with the hydrodealkylation of toluene as an example. ...

  18. 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...

  19. DESIGNING ENVIRONMENTALLY FRIENDLY CHEMICAL PROCESSES WITH FUGITIVE AND OPEN EMISSIONS

    EPA Science Inventory

    Designing a chemical process normally includes aspects of economic and environmental disciplines. In this work we describe methods to quickly and easily evaluate the economics and potential environmental impacts of a process, with the hydrodealkylation of toluene as an example. ...

  20. 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...

  1. 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

  2. A Framework for the Environmental Professional in the Chemical Industry.

    ERIC Educational Resources Information Center

    Priesing, Charles P.

    1982-01-01

    Addresses four areas of environmental concern in the chemical industry: (1) needs and responsibilities of environmental protection; (2) organization and distribution of environmental affairs within the corporate structure; (3) functions and operations associated with industrial environmental management; and (4) origins and tasks of the…

  3. A Framework for the Environmental Professional in the Chemical Industry.

    ERIC Educational Resources Information Center

    Priesing, Charles P.

    1982-01-01

    Addresses four areas of environmental concern in the chemical industry: (1) needs and responsibilities of environmental protection; (2) organization and distribution of environmental affairs within the corporate structure; (3) functions and operations associated with industrial environmental management; and (4) origins and tasks of the…

  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. Prediction of chemical carcinogenicity from molecular structure.

    PubMed

    Sun, Hongmao

    2004-01-01

    Carcinogens represent a serious threat to human health. In vivo determination of carcinogenicity is time-consuming and expensive, thus in silico models to predict chemical carcinogenicity are highly desirable for virtual screening of compound libraries of both pharmaceutically and other commercially interesting molecules. In the present study, a PLS-DA (partial least squares discriminant analysis) model was developed to predict carcinogenicities in each of four rodent models: male mouse (MM), female mouse (FM), male rat (MR), and female rat (FR). The data set that was used contained over 520 compounds from both the NTP and the FDA databases. All the models were built from the same molecular descriptor system, which is based on atom typing [Sun, H. J. Chem. Inf. Comput. Sci. 2004, 44, 748-757], enabling the comparison of atomic contributions to carcinogenicity with respect to species and gender. Using four components, the models were able to achieve excellent fitting and prediction, with r(2) = 0.987 and q(2) = 0.944 for MM, r(2) = 0.985 and q(2) = 0.950 for FM, r(2) = 0.989 and q(2) = 0.962 for MR, and r(2) = 0.990 and q(2) = 0.965 for FR. The models were further validated by response permutation testing and external validation, and the results indicated that the models were both statistically significant and predictive. Variable influence on projection (VIP) analysis identified the key atom types and fragments that contributed to carcinogenicities and response differences across species and gender.

  7. Predicting the Environmental Impact of Active Sonar

    NASA Astrophysics Data System (ADS)

    Duncan, Alec J.; McCauley, Robert D.; Maggi, Amos L.

    2004-11-01

    The effect of active sonar on marine animals, particularly mammals, has become a hot topic in recent times. The Australian Environmental Protection and Biodiversity Conservation Act 1999 obligates Defence to avoid significant environmental impacts from Navy activities including those which produce underwater sound such as active sonar. It is in the interests of all parties that these effects be modeled accurately to facilitate both the quantitative evaluation of the consequences of any proposed sonar trials, and the identification of suitable mitigation procedures. This paper discusses the received signal parameters that are of importance when predicting the effect of sonar systems on marine animals and techniques for modeling both the expected values of these parameters and their statistical fluctuations.

  8. Applications of predictive environmental strain models.

    PubMed

    Reardon, M J; Gonzalez, R R; Pandolf, K B

    1997-02-01

    Researchers at the U.S. Army Research Institute of Environmental Medicine have developed and validated numerical models capable of predicting the extent of physiologic strain and adverse terrain and weather-related medical consequences of military operations in harsh environments. A descriptive historical account is provided that details how physiologic models for hot and cold weather exposure have been integrated into portable field advisory devices, computer-based meteorologic planning software, and combat-oriented simulation systems. It is important that medical officers be aware of the existence of these types of decision support tools so that they can assure that outputs are interpreted in a balanced and medically realistic manner. Additionally, these modeling applications may facilitate timely preventive medicine planning and efficient dissemination of appropriate measures to prevent weather- and altitude-related illnesses and performance decrements. Such environmental response modeling applications may therefore be utilized to support deployment preventive medicine planning by field medical officers.

  9. EFFECTS OF ENVIRONMENTAL CHEMICALS ON FETAL TESTES TESTOSTERONE PRODUCTION

    EPA Science Inventory

    Effects of Environmental Chemicals on Fetal Testes Testosterone Production

    Lambright, CS , Wilson, VS , Furr, J, Wolf, CJ, Noriega, N, Gray, LE, Jr.
    US EPA, ORD/NHEERL/RTD, RTP, NC

    Exposure of pregnant rodents to certain environmental chemicals during criti...

  10. EFFECTS OF ENVIRONMENTAL CHEMICALS ON FETAL TESTES TESTOSTERONE PRODUCTION

    EPA Science Inventory

    Effects of Environmental Chemicals on Fetal Testes Testosterone Production

    Lambright, CS , Wilson, VS , Furr, J, Wolf, CJ, Noriega, N, Gray, LE, Jr.
    US EPA, ORD/NHEERL/RTD, RTP, NC

    Exposure of pregnant rodents to certain environmental chemicals during criti...

  11. Environmental chemical mutagens and genetic risks: Lessons from radiation genetics

    SciTech Connect

    Sankaranarayanan, K.

    1996-12-31

    The last three decades have witnessed substantial progress in the development and use of a variety of in vitro and in vivo assay systems for the testing of environmental chemicals which may pose a mutagenic hazard to humans. This is also true of basic studies in chemical mutagenesis on mechanisms, DNA repair, molecular dosimetry, structure-activity relationships, etc. However, the field of quantitative evaluation of genetic risks of environmental chemicals to humans is still in it infancy. This commentary addresses the question of how our experience in estimating genetic risks of exposure to ionizing radiation can be helpful in similar endeavors with environmental chemical mutagens. 24 refs., 3 tabs.

  12. Environmental analysis of the chemical release module. [space shuttle payload

    NASA Technical Reports Server (NTRS)

    Heppner, J. P.; Dubin, M.

    1980-01-01

    The environmental analysis of the Chemical Release Module (a free flying spacecraft deployed from the space shuttle to perform chemical release experiments) is reviewed. Considerations of possible effects of the injectants on human health, ionosphere, weather, ground based optical astronomical observations, and satellite operations are included. It is concluded that no deleterious environmental effects of widespread or long lasting nature are anticipated from chemical releases in the upper atmosphere of the type indicated for the program.

  13. Critical conceptualism in environmental modeling and prediction.

    PubMed

    Christakos, G

    2003-10-15

    Many important problems in environmental science and engineering are of a conceptual nature. Research and development, however, often becomes so preoccupied with technical issues, which are themselves fascinating, that it neglects essential methodological elements of conceptual reasoning and theoretical inquiry. This work suggests that valuable insight into environmental modeling can be gained by means of critical conceptualism which focuses on the software of human reason and, in practical terms, leads to a powerful methodological framework of space-time modeling and prediction. A knowledge synthesis system develops the rational means for the epistemic integration of various physical knowledge bases relevant to the natural system of interest in order to obtain a realistic representation of the system, provide a rigorous assessment of the uncertainty sources, generate meaningful predictions of environmental processes in space-time, and produce science-based decisions. No restriction is imposed on the shape of the distribution model or the form of the predictor (non-Gaussian distributions, multiple-point statistics, and nonlinear models are automatically incorporated). The scientific reasoning structure underlying knowledge synthesis involves teleologic criteria and stochastic logic principles which have important advantages over the reasoning method of conventional space-time techniques. Insight is gained in terms of real world applications, including the following: the study of global ozone patterns in the atmosphere using data sets generated by instruments on board the Nimbus 7 satellite and secondary information in terms of total ozone-tropopause pressure models; the mapping of arsenic concentrations in the Bangladesh drinking water by assimilating hard and soft data from an extensive network of monitoring wells; and the dynamic imaging of probability distributions of pollutants across the Kalamazoo river.

  14. Accurate prediction of the response of freshwater fish to a mixture of estrogenic chemicals.

    PubMed

    Brian, Jayne V; Harris, Catherine A; Scholze, Martin; Backhaus, Thomas; Booy, Petra; Lamoree, Marja; Pojana, Giulio; Jonkers, Niels; Runnalls, Tamsin; Bonfà, Angela; Marcomini, Antonio; Sumpter, John P

    2005-06-01

    Existing environmental risk assessment procedures are limited in their ability to evaluate the combined effects of chemical mixtures. We investigated the implications of this by analyzing the combined effects of a multicomponent mixture of five estrogenic chemicals using vitellogenin induction in male fathead minnows as an end point. The mixture consisted of estradiol, ethynylestradiol, nonylphenol, octylphenol, and bisphenol A. We determined concentration-response curves for each of the chemicals individually. The chemicals were then combined at equipotent concentrations and the mixture tested using fixed-ratio design. The effects of the mixture were compared with those predicted by the model of concentration addition using biomathematical methods, which revealed that there was no deviation between the observed and predicted effects of the mixture. These findings demonstrate that estrogenic chemicals have the capacity to act together in an additive manner and that their combined effects can be accurately predicted by concentration addition. We also explored the potential for mixture effects at low concentrations by exposing the fish to each chemical at one-fifth of its median effective concentration (EC50). Individually, the chemicals did not induce a significant response, although their combined effects were consistent with the predictions of concentration addition. This demonstrates the potential for estrogenic chemicals to act additively at environmentally relevant concentrations. These findings highlight the potential for existing environmental risk assessment procedures to underestimate the hazard posed by mixtures of chemicals that act via a similar mode of action, thereby leading to erroneous conclusions of absence of risk.

  15. Accurate Prediction of the Response of Freshwater Fish to a Mixture of Estrogenic Chemicals

    PubMed Central

    Brian, Jayne V.; Harris, Catherine A.; Scholze, Martin; Backhaus, Thomas; Booy, Petra; Lamoree, Marja; Pojana, Giulio; Jonkers, Niels; Runnalls, Tamsin; Bonfà, Angela; Marcomini, Antonio; Sumpter, John P.

    2005-01-01

    Existing environmental risk assessment procedures are limited in their ability to evaluate the combined effects of chemical mixtures. We investigated the implications of this by analyzing the combined effects of a multicomponent mixture of five estrogenic chemicals using vitellogenin induction in male fathead minnows as an end point. The mixture consisted of estradiol, ethynylestradiol, nonylphenol, octylphenol, and bisphenol A. We determined concentration–response curves for each of the chemicals individually. The chemicals were then combined at equipotent concentrations and the mixture tested using fixed-ratio design. The effects of the mixture were compared with those predicted by the model of concentration addition using biomathematical methods, which revealed that there was no deviation between the observed and predicted effects of the mixture. These findings demonstrate that estrogenic chemicals have the capacity to act together in an additive manner and that their combined effects can be accurately predicted by concentration addition. We also explored the potential for mixture effects at low concentrations by exposing the fish to each chemical at one-fifth of its median effective concentration (EC50). Individually, the chemicals did not induce a significant response, although their combined effects were consistent with the predictions of concentration addition. This demonstrates the potential for estrogenic chemicals to act additively at environmentally relevant concentrations. These findings highlight the potential for existing environmental risk assessment procedures to underestimate the hazard posed by mixtures of chemicals that act via a similar mode of action, thereby leading to erroneous conclusions of absence of risk. PMID:15929895

  16. Some environmental considerations relating to the interaction of the solid rocket motor exhaust with the atmosphere: Predicted chemical composition of exhaust species and predicted conditions for the formation of HCl aerosol

    NASA Technical Reports Server (NTRS)

    Rhein, R. A.

    1973-01-01

    The exhaust products of a solid rocket motor using as propellant 14% binder, 16% aluminum, and 70% (wt) ammonium perchlorate consist of hydrogen chloride, water, alumina, and other compounds. The equilibrium and some frozen compositions of the chemical species upon interaction with the atmosphere were computed. The conditions under which hydrogen chloride interacts with the water vapor in humid air to form an aerosol containing hydrochloric acid were computed for various weight ratios of air/exhaust products. These computations were also performed for the case of a combined SRM and hydrogen-oxygen rocket engine. Regimes of temperature and relative humidity where this aerosol is expected were identified. Within these regimes, the concentration of HCL in the aerosol and weight fraction of aerosol to gas phase were plotted. Hydrochloric acid aerosol formation was found to be particularly likely in cool humid weather.

  17. EVALUATING AND DESIGNING CHEMICAL PROCESSES FOR ENVIRONMENTAL SUSTAINABILITY

    EPA Science Inventory

    Chemicals and chemical processes are at the heart of most environmental problems. This isn't surprising since chemicals make up all of the products we use in our lives. The common use of cjhemicals makes them of high interest for systems analysis, particularly because of environ...

  18. EVALUATING AND DESIGNING CHEMICAL PROCESSES FOR ENVIRONMENTAL SUSTAINABILITY

    EPA Science Inventory

    Chemicals and chemical processes are at the heart of most environmental problems. This isn't surprising since chemicals make up all of the products we use in our lives. The common use of cjhemicals makes them of high interest for systems analysis, particularly because of environ...

  19. PREDICTION OF PHYSICOCHEMICAL PROCESSES FOR ENVIRONMENTAL MODELING BY COMPUTER

    EPA Science Inventory

    The major differences among behavioral profiles of molecules in the environment are attributable to their physicochemical properties. For most chemicals, only fragmentary knowledge exists about those properties that determine each compound's environmental fate. A chemical-by-ch...

  20. PREDICTION OF PHYSICOCHEMICAL PROCESSES FOR ENVIRONMENTAL MODELING BY COMPUTER

    EPA Science Inventory

    The major differences among behavioral profiles of molecules in the environment are attributable to their physicochemical properties. For most chemicals, only fragmentary knowledge exists about those properties that determine each compound's environmental fate. A chemical-by-ch...

  1. Chemical Fingerprinting of Materials Developed Due to Environmental Issues

    NASA Technical Reports Server (NTRS)

    Smith, Doris A.; McCool, A. (Technical Monitor)

    2000-01-01

    Instrumental chemical analysis methods are developed and used to chemically fingerprint new and modified External Tank materials made necessary by changing environmental requirements. Chemical fingerprinting can detect and diagnose variations in material composition. To chemically characterize each material, fingerprint methods are selected from an extensive toolbox based on the material's chemistry and the ability of the specific methods to detect the material's critical ingredients. Fingerprint methods have been developed for a variety of materials including Thermal Protection System foams, adhesives, primers, and composites.

  2. Toward a predictive theory for environmental enrichment.

    PubMed

    Watters, Jason V

    2009-11-01

    There have been many applications of and successes with environmental enrichment for captive animals. The theoretical spine upon which much enrichment work hangs largely describes why enrichment should work. Yet, there remains no clear understanding of how enrichment should be applied to achieve the most beneficial results. This lack of understanding may stem in part from the assumptions that underlie the application of enrichment by practitioners. These assumptions are derived from an understanding that giving animals choice and control in their environment stimulates their motivation to perform behaviors that may indicate a heightened state of well-being. Learning theory provides a means to question the manner in which these constructs are routinely applied, and converting learning theory's findings to optimality predictions suggests a particularly vexing paradox-that motivation to perform appears to be maintained best when acquiring a payoff for expressing the behavior is uncertain. This effect occurs even when the actual value of the payoff is the same for all schedules of certainty of payoff acquisition. The paradox can be resolved by invoking rewards of an alternative type, such as cognitive rewards, or through an understanding of how the average payoff changes with changes in the probability of reward. This model, with measures of the average change of the payoff, suggests testable scenarios by which practitioners can measure the quality of environmental uncertainty in enrichment programs.

  3. Simulation of Chronic Liver Injury Due to Environmental Chemicals

    EPA Science Inventory

    US EPA Virtual Liver (v-Liver) is a cellular systems model of hepatic tissues to predict the effects of chronic exposure to chemicals. Tens of thousands of chemicals are currently in commerce and hundreds more are introduced every year. Few of these chemicals have been adequate...

  4. Simulation of Chronic Liver Injury Due to Environmental Chemicals

    EPA Science Inventory

    US EPA Virtual Liver (v-Liver) is a cellular systems model of hepatic tissues to predict the effects of chronic exposure to chemicals. Tens of thousands of chemicals are currently in commerce and hundreds more are introduced every year. Few of these chemicals have been adequate...

  5. Computational Toxicology: Application in Environmental Chemicals

    EPA Science Inventory

    This chapter provides an overview of computational models that describe various aspects of the source-to-health effect continuum. Fate and transport models describe the release, transportation, and transformation of chemicals from sources of emission throughout the general envir...

  6. Computational Toxicology: Application in Environmental Chemicals

    EPA Science Inventory

    This chapter provides an overview of computational models that describe various aspects of the source-to-health effect continuum. Fate and transport models describe the release, transportation, and transformation of chemicals from sources of emission throughout the general envir...

  7. Predicting drugs side effects based on chemical-chemical interactions and protein-chemical interactions.

    PubMed

    Chen, Lei; Huang, Tao; Zhang, Jian; Zheng, Ming-Yue; Feng, Kai-Yan; Cai, Yu-Dong; Chou, Kuo-Chen

    2013-01-01

    A drug side effect is an undesirable effect which occurs in addition to the intended therapeutic effect of the drug. The unexpected side effects that many patients suffer from are the major causes of large-scale drug withdrawal. To address the problem, it is highly demanded by pharmaceutical industries to develop computational methods for predicting the side effects of drugs. In this study, a novel computational method was developed to predict the side effects of drug compounds by hybridizing the chemical-chemical and protein-chemical interactions. Compared to most of the previous works, our method can rank the potential side effects for any query drug according to their predicted level of risk. A training dataset and test datasets were constructed from the benchmark dataset that contains 835 drug compounds to evaluate the method. By a jackknife test on the training dataset, the 1st order prediction accuracy was 86.30%, while it was 89.16% on the test dataset. It is expected that the new method may become a useful tool for drug design, and that the findings obtained by hybridizing various interactions in a network system may provide useful insights for conducting in-depth pharmacological research as well, particularly at the level of systems biomedicine.

  8. Predicting Drugs Side Effects Based on Chemical-Chemical Interactions and Protein-Chemical Interactions

    PubMed Central

    Chen, Lei; Huang, Tao; Zhang, Jian; Zheng, Ming-Yue; Feng, Kai-Yan; Cai, Yu-Dong; Chou, Kuo-Chen

    2013-01-01

    A drug side effect is an undesirable effect which occurs in addition to the intended therapeutic effect of the drug. The unexpected side effects that many patients suffer from are the major causes of large-scale drug withdrawal. To address the problem, it is highly demanded by pharmaceutical industries to develop computational methods for predicting the side effects of drugs. In this study, a novel computational method was developed to predict the side effects of drug compounds by hybridizing the chemical-chemical and protein-chemical interactions. Compared to most of the previous works, our method can rank the potential side effects for any query drug according to their predicted level of risk. A training dataset and test datasets were constructed from the benchmark dataset that contains 835 drug compounds to evaluate the method. By a jackknife test on the training dataset, the 1st order prediction accuracy was 86.30%, while it was 89.16% on the test dataset. It is expected that the new method may become a useful tool for drug design, and that the findings obtained by hybridizing various interactions in a network system may provide useful insights for conducting in-depth pharmacological research as well, particularly at the level of systems biomedicine. PMID:24078917

  9. In silico environmental chemical science: properties and processes from statistical and computational modelling

    SciTech Connect

    Tratnyek, Paul G.; Bylaska, Eric J.; Weber, Eric J.

    2017-01-01

    Quantitative structure–activity relationships (QSARs) have long been used in the environmental sciences. More recently, molecular modeling and chemoinformatic methods have become widespread. These methods have the potential to expand and accelerate advances in environmental chemistry because they complement observational and experimental data with “in silico” results and analysis. The opportunities and challenges that arise at the intersection between statistical and theoretical in silico methods are most apparent in the context of properties that determine the environmental fate and effects of chemical contaminants (degradation rate constants, partition coefficients, toxicities, etc.). The main example of this is the calibration of QSARs using descriptor variable data calculated from molecular modeling, which can make QSARs more useful for predicting property data that are unavailable, but also can make them more powerful tools for diagnosis of fate determining pathways and mechanisms. Emerging opportunities for “in silico environmental chemical science” are to move beyond the calculation of specific chemical properties using statistical models and toward more fully in silico models, prediction of transformation pathways and products, incorporation of environmental factors into model predictions, integration of databases and predictive models into more comprehensive and efficient tools for exposure assessment, and extending the applicability of all the above from chemicals to biologicals and materials.

  10. In silico environmental chemical science: properties and processes from statistical and computational modelling.

    PubMed

    Tratnyek, Paul G; Bylaska, Eric J; Weber, Eric J

    2017-03-22

    Quantitative structure-activity relationships (QSARs) have long been used in the environmental sciences. More recently, molecular modeling and chemoinformatic methods have become widespread. These methods have the potential to expand and accelerate advances in environmental chemistry because they complement observational and experimental data with "in silico" results and analysis. The opportunities and challenges that arise at the intersection between statistical and theoretical in silico methods are most apparent in the context of properties that determine the environmental fate and effects of chemical contaminants (degradation rate constants, partition coefficients, toxicities, etc.). The main example of this is the calibration of QSARs using descriptor variable data calculated from molecular modeling, which can make QSARs more useful for predicting property data that are unavailable, but also can make them more powerful tools for diagnosis of fate determining pathways and mechanisms. Emerging opportunities for "in silico environmental chemical science" are to move beyond the calculation of specific chemical properties using statistical models and toward more fully in silico models, prediction of transformation pathways and products, incorporation of environmental factors into model predictions, integration of databases and predictive models into more comprehensive and efficient tools for exposure assessment, and extending the applicability of all the above from chemicals to biologicals and materials.

  11. 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...

  12. 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 ...

  13. DESIGNING ENVIRONMENTAL, ECONOMIC AND ENERGY EFFICIENT CHEMICAL PROCESSES

    EPA Science Inventory

    The design and improvement of chemical processes can be very challenging. The earlier energy conservation, process economics and environmental aspects are incorporated into the process development, the easier and less expensive it is to alter the process design. Process emissio...

  14. DESIGNING ENVIRONMENTAL, ECONOMIC AND ENERGY EFFICIENT CHEMICAL PROCESSES

    EPA Science Inventory

    The design and improvement of chemical processes can be very challenging. The earlier energy conservation, process economics and environmental aspects are incorporated into the process development, the easier and less expensive it is to alter the process design. Process emissio...

  15. 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 ...

  16. Chemical Aging of Environmentally Friendly Cleaners

    NASA Technical Reports Server (NTRS)

    Biegert, L. L.; Evans, K. B.; Olsen, B. D.; Weber, B. L.

    2001-01-01

    Use of cleaners in the manufacturing area demands bottles that will hold a sufficient amount of material and allow for easy and controlled dispensing by the operator without contamination or material leaching from the bottle. The manufacturing storage conditions are also a factor that may affect cleaner chemical integrity and its potential to leave a residue on the part. A variety of squeeze bottles stored in mild (72 F, 10% R.H., dark) and harsh (105 F, 50% R.H., fluorescent lighting) conditions were evaluated to determine the effect of environment and bottle exposure on ozone depleting chemicals (ODC) cleaners chemical composition. Low Density Polyethylene (LDPE) bottles were found to be quite permeable to all the cleaners evaluated in this study indicating this bottle type should not be used in the manufacturing area. Fluorinated Polyethylene (FLPE) bottles showed little cleaner loss and change in cleaner chemical composition over time suggesting these bottles would be acceptable for use. Chemical analysis indicates limonene containing cleaners show increased non-volatile residue (NVR) content with storage under harsh conditions. Some cleaners use BHT (butylated hydroxytoluene) as stabilizer and to protect against limonene oxidation. Under harsh conditions, BHT was quickly depleted resulting in higher NVR levels.

  17. Chemical Aging of Environmentally Friendly Cleaners

    NASA Technical Reports Server (NTRS)

    Biegert, L. L.; Evans, K. B.; Olsen, B. D.; Weber, B. L.

    2001-01-01

    Use of cleaners in the manufacturing area demands bottles that will hold a sufficient amount of material and allow for easy and controlled dispensing by the operator without contamination or material leaching from the bottle. The manufacturing storage conditions are also a factor that may affect cleaner chemical integrity and its potential to leave a residue on the part. A variety of squeeze bottles stored in mild (72 F, 10% R.H., dark) and harsh (105 F, 50% R.H., fluorescent lighting) conditions were evaluated to determine the effect of environment and bottle exposure on ozone depleting chemicals (ODC) cleaners chemical composition. Low Density Polyethylene (LDPE) bottles were found to be quite permeable to all the cleaners evaluated in this study indicating this bottle type should not be used in the manufacturing area. Fluorinated Polyethylene (FLPE) bottles showed little cleaner loss and change in cleaner chemical composition over time suggesting these bottles would be acceptable for use. Chemical analysis indicates limonene containing cleaners show increased non-volatile residue (NVR) content with storage under harsh conditions. Some cleaners use BHT (butylated hydroxytoluene) as stabilizer and to protect against limonene oxidation. Under harsh conditions, BHT was quickly depleted resulting in higher NVR levels.

  18. 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.

  19. The Molecular Recognition Paradigm of Environmental Chemicals with Biomacromolecules.

    PubMed

    Zhang, Wenjing; Pan, Liumeng; Wang, Haifei; Lv, Xuan; Ding, Keke

    2017-01-01

    The interactions of ligands with biomacromolecules play a fundamental role in almost all bioprocesses occuring in living organisms. The binding of ligands can cause the conformational changes of biomacromolecules, possibly affecting their physiological functions. The interactions of ligands with biomacromolecules are thus becoming a research hotspot. However, till now, there still lacks a systematic compilation of review with the focus on the interactions between environmental chemicals and biomacromolecules. In this review, we focus on the molecular recognition paradigm of environmental chemicals with biomacromolecules and chemical basis for driving the complex formation. The state-of-the-art review on in vitro and in silico studies on interaction of organic chemicals with transport proteins, nuclear receptors and CYP450 enzymes was provided, and the enantioselective interactions of chiral environmental chemicals was also mentioned.

  20. Chemical Aging of Environmentally Friendly Cleaners

    NASA Technical Reports Server (NTRS)

    Evans, K.; Biegert, L.; Olsen, B.; Weber, B.; McCool, Alex (Technical Monitor)

    2001-01-01

    Use of cleaners in the manufacturing area demands bottles that will hold a sufficient amount of material and allow for easy and controlled dispensing by the operator without contamination or material leaching from the bottle. The manufacturing storage conditions are also a factor that may affect cleaner chemical integrity and its potential to leave a residue on the part. A variety of squeeze bottles stored in mild (72 F, 10 % R.H., dark) and harsh (105 F, 50 % R.H., fluorescent lighting) conditions were evaluated to determine the effect of environment and bottle exposure on the chemical composition of TCA (1,1,1 trichloroethane) replacement solvents. Low Density Polyethylene (LDPE) bottles were found to be quite permeable to all the cleaners evaluated in this study indicating this bottle type should not be used in the manufacturing area. Fluorinated Polyethylene (FLPE) bottles showed little cleaner loss and change in cleaner chemical composition over time suggesting these bottles would be acceptable for use. Chemical analysis indicates limonene-containing cleaners show increased non-volatile residue (NVR) content with storage under harsh conditions. Some cleaners use BHT (butylated hydroxytoluene) as stabilizer and to protect against limonene oxidation. Under harsh conditions, BHT was quickly depleted resulting in higher NVR levels.

  1. RAPID SCREENING OF ENVIRONMENTAL CHEMICALS FOR ESTROGEN RECEPTOR BINDING CAPACITY

    EPA Science Inventory

    Over the last few years, an increased awareness of endocrine disrupting chemicals (EDCs) and their potential to affect wildlife and humans has produced a demand for practical screening methods to identify endocrine activity in a wide range of environmental and industrial chemical...

  2. RAPID SCREENING OF ENVIRONMENTAL CHEMICALS FOR ESTROGEN RECEPTOR BINDING CAPACITY

    EPA Science Inventory

    Over the last few years, an increased awareness of endocrine disrupting chemicals (EDCs) and their potential to affect wildlife and humans has produced a demand for practical screening methods to identify endocrine activity in a wide range of environmental and industrial chemical...

  3. A Chemical Properties Simulator to Support Integrated Environmental Modeling

    EPA Science Inventory

    Users of Integrated Environmental Modeling (IEM) systems are responsible for defining individual chemicals and their properties, a process that is time-consuming at best and overwhelming at worst, especially for new chemicals with new structures. A software tool is needed to allo...

  4. A Chemical Properties Simulator to Support Integrated Environmental Modeling (proceeding)

    EPA Science Inventory

    Users of Integrated Environmental Modeling (IEM) systems are responsible for defining individual chemicals and their properties, a process that is time-consuming at best and overwhelming at worst, especially for new chemicals with new structures. A software tool is needed to allo...

  5. A Chemical Properties Simulator to Support Integrated Environmental Modeling

    EPA Science Inventory

    Users of Integrated Environmental Modeling (IEM) systems are responsible for defining individual chemicals and their properties, a process that is time-consuming at best and overwhelming at worst, especially for new chemicals with new structures. A software tool is needed to allo...

  6. A Chemical Properties Simulator to Support Integrated Environmental Modeling (proceeding)

    EPA Science Inventory

    Users of Integrated Environmental Modeling (IEM) systems are responsible for defining individual chemicals and their properties, a process that is time-consuming at best and overwhelming at worst, especially for new chemicals with new structures. A software tool is needed to allo...

  7. CHEMICAL INDUCTION MIXER VERIFICATION - ENVIRONMENTAL TECHNOLOGY VERIFICATION PROGRAM

    EPA Science Inventory

    The Wet-Weather Flow Technologies Pilot of the Environmental Technology Verification (ETV) Program, which is supported by the U.S. Environmental Protection Agency and facilitated by NSF International, has recently evaluated the performance of chemical induction mixers used for di...

  8. CHEMICAL INDUCTION MIXER VERIFICATION - ENVIRONMENTAL TECHNOLOGY VERIFICATION PROGRAM

    EPA Science Inventory

    The Wet-Weather Flow Technologies Pilot of the Environmental Technology Verification (ETV) Program, which is supported by the U.S. Environmental Protection Agency and facilitated by NSF International, has recently evaluated the performance of chemical induction mixers used for di...

  9. ANIMALS AS SENTINELS OF HUMAN HEALTH HAZARDS OF ENVIRONMENTAL CHEMICALS

    EPA Science Inventory

    A workshop titled "Using Sentinel Species Data to Address the Potential Human Health Effects of Chemicals in the Environmnet," sponsored by the U.S. Army Center for Environmental Health Research, the National Center for Environmental Assessment of the EPA, and the Agency for Toxi...

  10. ANIMALS AS SENTINELS OF HUMAN HEALTH HAZARDS OF ENVIRONMENTAL CHEMICALS

    EPA Science Inventory

    A workshop titled "Using Sentinel Species Data to Address the Potential Human Health Effects of Chemicals in the Environmnet," sponsored by the U.S. Army Center for Environmental Health Research, the National Center for Environmental Assessment of the EPA, and the Agency for Toxi...

  11. Biomonitoring human exposure to environmental carcinogenic chemicals.

    PubMed

    Farmer, P B; Sepai, O; Lawrence, R; Autrup, H; Sabro Nielsen, P; Vestergård, A B; Waters, R; Leuratti, C; Jones, N J; Stone, J; Baan, R A; van Delft, J H; Steenwinkel, M J; Kyrtopoulos, S A; Souliotis, V L; Theodorakopoulos, N; Bacalis, N C; Natarajan, A T; Tates, A D; Haugen, A; Andreassen, A; Ovrebø, S; Shuker, D E; Amaning, K S; Castelain, P

    1996-07-01

    A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of second biological effects (mutation and cytogenetic damage). Adduct detection at the level of DNA or protein (haemoglobin) was carried out by 32P-postlabelling, immunochemical, HPLC or mass spectrometric methods. Urinary excretion products resulting from DNA damage were also estimated (immunochemical assay, mass spectrometry). The measurement of adducts was focused on those from genotoxicants that result from petrochemical combustion or processing, e.g. low-molecular-weight alkylating agents, PAHs and compounds that cause oxidative DNA damage. Cytogenetic analysis of lymphocytes was undertaken (micronuclei, chromosome aberrations and sister chromatid exchanges) and mutation frequency was estimated at a number of loci including the hprt gene and genes involving in cancer development. Blood and urine samples from individuals exposed to urban pollution were collected. Populations exposed through occupational or medical sources to larger amounts of some of the genotoxic compounds present in the environmental samples were used as positive controls for the environmentally exposed population. Samples from rural areas were used as negative controls. The project has led to new, more sensitive and more selective approaches for detecting carcinogen-induced damage to DNA and proteins, and subsequent biological effects. These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in workers in a coke oven plant, garage workers exposed to diesel exhaust and workers exposed to ethylene oxide in a sterilization plant. Dose reponse and adduct repair were studied for methylated adducts in patients treated with methylating cytostatic drugs

  12. Deconstructing environmental predictability: seasonality, environmental colour and the biogeography of marine life histories.

    PubMed

    Marshall, Dustin J; Burgess, Scott C

    2015-02-01

    Environmental predictability is predicted to shape the evolution of life histories. Two key types of environmental predictability, seasonality and environmental colour, may influence life-history evolution independently but formal considerations of both and how they relate to life history are exceedingly rare. Here, in a global biogeographical analysis of over 800 marine invertebrates, we explore the relationships between both forms of environmental predictability and three fundamental life-history traits: location of larval development (aplanktonic vs. planktonic), larval developmental mode (feeding vs. non-feeding) and offspring size. We found that both dispersal potential and offspring size related to environmental predictability, but the relationships depended on both the environmental factor as well as the type of predictability. Environments that were more seasonal in food availability had a higher prevalence of species with a planktonic larval stage. Future studies should consider both types of environmental predictability as each can strongly affect life-history evolution. © 2014 John Wiley & Sons Ltd/CNRS.

  13. Predicting environmental fate parameters with infrared spectroscopy.

    EPA Science Inventory

    One of the principal uncertainties associated with risk assessments of organic chemicals in the environment is the lack of chemical-specific values that quantify the many processes determining the chemical's transport and transformation. Because it is not feasible to measure the ...

  14. Predicting environmental fate parameters with infrared spectroscopy.

    EPA Science Inventory

    One of the principal uncertainties associated with risk assessments of organic chemicals in the environment is the lack of chemical-specific values that quantify the many processes determining the chemical's transport and transformation. Because it is not feasible to measure the ...

  15. Perceived Vulnerability to Disease Predicts Environmental Attitudes

    ERIC Educational Resources Information Center

    Prokop, Pavol; Kubiatko, Milan

    2014-01-01

    Investigating predictors of environmental attitudes may bring valuable benefits in terms of improving public awareness about biodiversity degradation and increased pro-environmental behaviour. Here we used an evolutionary approach to study environmental attitudes based on disease-threat model. We hypothesized that people vulnerable to diseases may…

  16. Perceived Vulnerability to Disease Predicts Environmental Attitudes

    ERIC Educational Resources Information Center

    Prokop, Pavol; Kubiatko, Milan

    2014-01-01

    Investigating predictors of environmental attitudes may bring valuable benefits in terms of improving public awareness about biodiversity degradation and increased pro-environmental behaviour. Here we used an evolutionary approach to study environmental attitudes based on disease-threat model. We hypothesized that people vulnerable to diseases may…

  17. Family Environmental and Genetic Influences on Children's Future Chemical Dependency.

    ERIC Educational Resources Information Center

    Kumpfer, Karol L.; DeMarsh, Joseph

    1985-01-01

    Discusses the following in relation to their predictability to future drug abuse in youth: (1) susceptibility of children of chemically dependent parents; (2) genetic transmutation; (3) family structure and management; (4) socialization; and (5) cognitive family characteristics. (Author/LHW)

  18. Synergistic activation of estrogen receptor with combinations of environmental chemicals

    SciTech Connect

    Arnold, S.F.; Klotz, D.M.; Collins, B.M.

    1996-06-07

    Certain chemicals in the environment are estrogenic. The low potencies of the compounds, when studied singly, suggest that they may have little effect on biological systems. The estrogenic potencies of combinations of such chemicals were screened in a simple yeast estrogen potencies of combination of such chemicals were screened in a simple yeast estrogen systems (YES) containing human estrogen receptor (hER). Combinations of two weak environmental estrogens, such as dieldrin, endosulfan, or toxaphene, were 100 times as potent in hER-mediated transactivation as any chemical alone. Hydroxylated polychlorinated biphenyls shown previously to synergistically alter sexual development in turtles also synergized in the YES. The synergistic interaction of chemical mixtures with the estrogen receptor may have profound environmental implications. These results may represent a previously uncharacterized level of regulation of estrogen-associated responses. 32 refs., 3 figs., 3 tabs.

  19. Predicting Anatomical Therapeutic Chemical (ATC) classification of drugs by integrating chemical-chemical interactions and similarities.

    PubMed

    Chen, Lei; Zeng, Wei-Ming; Cai, Yu-Dong; Feng, Kai-Yan; Chou, Kuo-Chen

    2012-01-01

    The Anatomical Therapeutic Chemical (ATC) classification system, recommended by the World Health Organization, categories drugs into different classes according to their therapeutic and chemical characteristics. For a set of query compounds, how can we identify which ATC-class (or classes) they belong to? It is an important and challenging problem because the information thus obtained would be quite useful for drug development and utilization. By hybridizing the informations of chemical-chemical interactions and chemical-chemical similarities, a novel method was developed for such purpose. It was observed by the jackknife test on a benchmark dataset of 3,883 drug compounds that the overall success rate achieved by the prediction method was about 73% in identifying the drugs among the following 14 main ATC-classes: (1) alimentary tract and metabolism; (2) blood and blood forming organs; (3) cardiovascular system; (4) dermatologicals; (5) genitourinary system and sex hormones; (6) systemic hormonal preparations, excluding sex hormones and insulins; (7) anti-infectives for systemic use; (8) antineoplastic and immunomodulating agents; (9) musculoskeletal system; (10) nervous system; (11) antiparasitic products, insecticides and repellents; (12) respiratory system; (13) sensory organs; (14) various. Such a success rate is substantially higher than 7% by the random guess. It has not escaped our notice that the current method can be straightforwardly extended to identify the drugs for their 2(nd)-level, 3(rd)-level, 4(th)-level, and 5(th)-level ATC-classifications once the statistically significant benchmark data are available for these lower levels.

  20. Environmental and safety obligations of the Chemical Weapons Convention

    SciTech Connect

    Tanzman, E.A.

    1994-04-07

    Among its many unique and precedent-setting provisions, the Chemical Weapons Convention (CWC) includes important requirements for States Parties to protect the public safety and the environment in the course of carrying out the treaty. These obligations will apply to the destruction of chemical weapons, of former chemical weapons production facilities, and to other activities under the Convention such as the verification scheme. This morning, I will briefly discuss the Convention`s safety and environmental obligations, concentrating on their effects in this country as the United States chemical weapons stockpile is destroyed.

  1. Environmental neurotoxicity of chemicals and radiation

    SciTech Connect

    Verity, M.A. )

    1993-06-01

    Epidemiologic and societal concerns continue to stimulate studies in the field of environmental neurotoxicology. Although the role of heavy metals, aluminum, and iron are unclear in the etiology of human neurodegenerative disorders, these toxins have provided fertile ground for in vivo and in vitro experimental studies to elucidate their role in neurotoxic injury. Experimental models of clinical syndromes are discussed with special relevance to developmental neurotoxicology. Cycloleucine, tellurium, and 1,3-dinitrobenzene provide models of subacute combined degeneration, primary peripheral nerve demyelination, and thiamine deficiency-like lesions, respectively. Increasing attention is being given to irradiation neurotoxicity, especially in the developing or young central nervous system. A fuller understanding of the pathogenesis of low-dose irradiation injury allows for a clearer understanding of its neurobiology and also provides a more rational approach to understanding an interventional therapy associated with brain irradiation for childhood neoplasia. 43 refs.

  2. Isotope labeled immunoassay for environmental chemical detection

    SciTech Connect

    Velez, M.M.

    1994-05-06

    Altrazine, one of the most heavily used agricultural pesticides in North America, has been identified as a major groundwater contaminant in the U.S. Research provides evidence that under certain conditions atrazine and some of its derivatives may prove to be carcinogenic and mutagenic. Immunossays are one of the most powerful of all analytical immunochemical techniques. They employ a wide range of methods to detect and quantitate antigens or antibodies, and to study the structure of antigens. With the appropriate assay, they can be remarkably quick and easy, to yield information that would be difficult to determine by other techniques. The development of the appropriate assay; however, requires clean and precise separation of antigens bound to antibodies from those that remain free. Sensitive assays depend on quantification of these bound antigens at very low levels. We are making direct and competitive immunoassays with atrazine and its antibodies using accelerator mass spectrometry (AMS) in order to obtain a sensitive immunoassay for atrazine in environmental samples.

  3. Environmental Influences on Reproductive Health, the Importance of Chemical Exposures

    PubMed Central

    Wang, Aolin; Padula, Amy; Sirota, Marina; Woodruff, Tracey J.

    2016-01-01

    Unstructured Abstract Chemical exposures during pregnancy can have a profound and life-long impact on human health. Due to the omnipresence of chemicals in our daily life, there is continuous contact with chemicals in food, water, air and consumer products. Consequently, human biomonitoring studies show that pregnant women around the globe are exposed to a variety of chemicals. In this review, we provide a summary of current data on maternal and fetal exposure as well as health consequences from these exposures. We review several chemical classes including polychlorinated biphenyls (PCBs), perfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), phenols, phthalates, pesticides, and metals. Additionally, we discuss environmental disparities and vulnerable populations, and future research directions. We conclude by providing some recommendations for prevention of chemical exposure and its adverse reproductive health consequences. PMID:27513554

  4. Environmental influences on reproductive health: the importance of chemical exposures.

    PubMed

    Wang, Aolin; Padula, Amy; Sirota, Marina; Woodruff, Tracey J

    2016-09-15

    Chemical exposures during pregnancy can have a profound and life-long impact on human health. Because of the omnipresence of chemicals in our daily life, there is continuous contact with chemicals in food, water, air, and consumer products. Consequently, human biomonitoring studies show that pregnant women around the globe are exposed to a variety of chemicals. In this review we provide a summary of current data on maternal and fetal exposure, as well as health consequences from these exposures. We review several chemical classes, including polychlorinated biphenyls, perfluoroalkyl substances, polybrominated diphenyl ethers, phenols, phthalates, pesticides, and metals. Additionally, we discuss environmental disparities and vulnerable populations, and future research directions. We conclude by providing some recommendations for prevention of chemical exposure and its adverse reproductive health consequences. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. TSCA Work Plan Chemical Technical Supplement – Physicochemical Properties and Environmental Fate of the Brominated Phthalates Cluster (BPC) Chemicals

    EPA Pesticide Factsheets

    TSCA Work Plan Chemical Technical Supplement – Physicochemical Properties and Environmental Fate of the Brominated Phthalates Cluster (BPC) Chemicals -- Brominated Phthalates Cluster Flame Retardants.

  6. How can Databases assist with the Prediction of Chemical Compounds?

    PubMed Central

    Schön, J Christian

    2014-01-01

    An overview is given on the ways databases can be employed to aid in the prediction of chemical compounds, in particular inorganic crystalline compounds. Methods currently employed and possible future approaches are discussed. PMID:26213422

  7. Environmental fate and transport of chemical signatures from buried landmines -- Screening model formulation and initial simulations

    SciTech Connect

    Phelan, J.M.; Webb, S.W.

    1997-06-01

    The fate and transport of chemical signature molecules that emanate from buried landmines is strongly influenced by physical chemical properties and by environmental conditions of the specific chemical compounds. Published data have been evaluated as the input parameters that are used in the simulation of the fate and transport processes. A one-dimensional model developed for screening agricultural pesticides was modified and used to simulate the appearance of a surface flux above a buried landmine, estimate the subsurface total concentration, and show the phase specific concentrations at the ground surface. The physical chemical properties of TNT cause a majority of the mass released to the soil system to be bound to the solid phase soil particles. The majority of the transport occurs in the liquid phase with diffusion and evaporation driven advection of soil water as the primary mechanisms for the flux to the ground surface. The simulations provided herein should only be used for initial conceptual designs of chemical pre-concentration subsystems or complete detection systems. The physical processes modeled required necessary simplifying assumptions to allow for analytical solutions. Emerging numerical simulation tools will soon be available that should provide more realistic estimates that can be used to predict the success of landmine chemical detection surveys based on knowledge of the chemical and soil properties, and environmental conditions where the mines are buried. Additional measurements of the chemical properties in soils are also needed before a fully predictive approach can be confidently applied.

  8. Dutch plan sets environmental targets for chemical industry

    SciTech Connect

    Layman, P.L. )

    1993-11-01

    The Dutch effort is a covenant--established between the nation's government and its chemical industry--to move the Netherlands forward in sustainable development, toward the year 2010, by cutting emissions from chemical production at both large and small chemical companies. The agreement is even accepted, in principle, by many of the country's tough environmental groups, although they have serious reservations on such aspects as timing and extent of the efforts. The chemical industry has committed itself to supporting the national plant, which sets forth firm sectoral goals for 2000 and targets for 2010. The government, in turn, has pledged to not unilaterally change its standards or requirements during this time. The Dutch government thereby achieves its strategic goals of lessened environmental pollution. And the industry's managers can incorporate the goals into their long-term investment planning.

  9. Chemical Genomics Profiling of Environmental Chemical Modulation of Human Nuclear Receptors

    EPA Science Inventory

    The large and increasing number of chemicals released into the environment demand more efficient and cost effective approaches for assessing environmental chemical toxicity. The U.S. Tox21 program has responded to this challenge by proposing alternative strategies for toxicity te...

  10. Chemical Genomics Profiling of Environmental Chemical Modulation of Human Nuclear Receptors

    EPA Science Inventory

    The large and increasing number of chemicals released into the environment demand more efficient and cost effective approaches for assessing environmental chemical toxicity. The U.S. Tox21 program has responded to this challenge by proposing alternative strategies for toxicity te...

  11. Developmental Exposure to Environmental Chemicals and Metabolic Changes in Children.

    PubMed

    Russ, Karin; Howard, Sarah

    2016-08-01

    The incidence of childhood obesity, type 2 diabetes, and other forms of metabolic disease have been rising over the past several decades. Although diet and physical activity play important roles in these trends, other environmental factors also may contribute to this significant public health issue. In this article, we discuss the possibility that widespread exposure to endocrine-disrupting chemicals (EDCs) may contribute to the development of metabolic diseases in children. We summarize the epidemiological evidence on exposure to environmental chemicals during early development and metabolic outcomes in infants and children. Prenatal exposure to EDCs, particularly the persistent organic pollutant DDT and its metabolite DDE, may influence growth patterns during infancy and childhood. The altered growth patterns associated with EDCs vary according to exposure level, sex, exposure timing, pubertal status, and age at which growth is measured. Early exposure to air pollutants also is linked to impaired metabolism in infants and children. As a result of these and other studies, professional health provider societies have called for a reduction in environmental chemical exposures. We summarize the resources available to health care providers to counsel patients on how to reduce chemical exposures. We conclude with a discussion of environmental policies that address chemical exposures and ultimately aim to improve public health.

  12. Chemicals and environmentally caused diseases in developing countries

    SciTech Connect

    Jamall, I.S.; Davis, B. )

    1991-06-01

    This chapter discusses international aspects of diseases resulting from exposure to chemical pollutants in the environment, with an emphasis on developing countries. These countries share many of the same problems of air, water, and pesticide pollution that face the more industrialized countries. In developing countries, however, the problems are compounded by a number of unique situations, viz., economic priorities, high burden of infectious diseases, impoverishment, and absence of a regulatory framework for the disposal of toxic chemicals. This discussion emphasizes the importance of interactions among toxicants, malnutrition, and infectious diseases for both urban and rural populations insofar as these interactions contribute to disease. Toxicants not only produce disease directly but also exacerbate diseases with other causes. Specific examples from developing countries demonstrate how human health effects from exposures to environmental chemicals can be assessed. While they do not strictly fall under the rubric of developing countries, the public health consequences of inadequate control of environmental pollution in the East European countries should demonstrate the magnitude of the problem, except that in developing countries the public health consequence of environmental chemicals will be aggravated by the widespread malnutrition and high prevalence of infectious diseases. Much needs to be done before we can adequately quantify the contribution of environmental chemicals to morbidity and mortality in developing countries with the level of sophistication now evident in the charting of infectious diseases in these countries. 52 references.

  13. Deciphering Diseases and Biological Targets for Environmental Chemicals using Toxicogenomics Networks

    PubMed Central

    Audouze, Karine; Juncker, Agnieszka Sierakowska; Roque, Francisco J. S. S. A.; Krysiak-Baltyn, Konrad; Weinhold, Nils; Taboureau, Olivier; Jensen, Thomas Skøt; Brunak, Søren

    2010-01-01

    Exposure to environmental chemicals and drugs may have a negative effect on human health. A better understanding of the molecular mechanism of such compounds is needed to determine the risk. We present a high confidence human protein-protein association network built upon the integration of chemical toxicology and systems biology. This computational systems chemical biology model reveals uncharacterized connections between compounds and diseases, thus predicting which compounds may be risk factors for human health. Additionally, the network can be used to identify unexpected potential associations between chemicals and proteins. Examples are shown for chemicals associated with breast cancer, lung cancer and necrosis, and potential protein targets for di-ethylhexyl-phthalate, 2,3,7,8-tetrachlorodibenzo-p-dioxin, pirinixic acid and permethrine. The chemical-protein associations are supported through recent published studies, which illustrate the power of our approach that integrates toxicogenomics data with other data types. PMID:20502671

  14. Environmental laws regulating chemicals: Uses of information in decision making under environmental statutes

    SciTech Connect

    Gaba, J.M.

    1990-12-31

    Three areas are addressed in this paper: generic issues that arise simply in the process of decision-making under environmental statutes; different decision-making standards under various environmental statutes; and efforts to legislate a {open_quotes}safe{close_quotes} or {open_quotes}acceptable{close_quotes} risk from exposure to carcinogenic chemicals.

  15. Environmental Impact on Vascular Development Predicted by High Throughput Screening

    EPA Science Inventory

    Understanding health risks to embryonic development from exposure to environmental chemicals is a significant challenge given the diverse chemical landscape and paucity of data for most of these compounds. High throughput screening (HTS) in EPA’s ToxCastTM project provides vast d...

  16. Environmental Impact on Vascular Development Predicted by High Throughput Screening

    EPA Science Inventory

    Understanding health risks to embryonic development from exposure to environmental chemicals is a significant challenge given the diverse chemical landscape and paucity of data for most of these compounds. High throughput screening (HTS) in EPA’s ToxCastTM project provides vast d...

  17. PREDICTING EVAPORATION RATES AND TIMES FOR SPILLS OF CHEMICAL MIXTURES

    EPA Science Inventory


    Spreadsheet and short-cut methods have been developed for predicting evaporation rates and evaporation times for spills (and constrained baths) of chemical mixtures. Steady-state and time-varying predictions of evaporation rates can be made for six-component mixtures, includ...

  18. PREDICTING EVAPORATION RATES AND TIMES FOR SPILLS OF CHEMICAL MIXTURES

    EPA Science Inventory


    Spreadsheet and short-cut methods have been developed for predicting evaporation rates and evaporation times for spills (and constrained baths) of chemical mixtures. Steady-state and time-varying predictions of evaporation rates can be made for six-component mixtures, includ...

  19. Improving confidence in (Q)SAR predictions under Canada's Chemicals Management Plan - a chemical space approach.

    PubMed

    Kulkarni, S A; Benfenati, E; Barton-Maclaren, T S

    2016-10-20

    One of the key challenges of Canada's Chemicals Management Plan (CMP) is assessing chemicals with limited/no empirical hazard data for their risk to human health. In some instances, these chemicals have not been tested broadly for their toxicological potency; as such, limited information exists on their potential to induce human health effects following exposure. Although (quantitative) structure activity relationship ((Q)SAR) models are able to generate predictions to address data gaps for certain toxicological endpoints, the confidence in predictions also needs to be addressed. One way to address this issue is to apply a chemical space approach. This approach uses international toxicological databases, for example, those available in the Organisation for Economic Co-operation and Development (OECD) QSAR Toolbox. The approach,assesses a model's ability to predict the potential hazards of chemicals that have limited hazard data that require assessment under the CMP when compared to a larger, data-rich chemical space that is structurally similar to chemicals of interest. This evaluation of a model's predictive ability makes (Q)SAR analysis more transparent and increases confidence in the application of these predictions in a risk-assessment context. Using this approach, predictions for such chemicals obtained from four (Q)SAR models were successfully classified into high, medium and low confidence levels to better inform their use in decision-making.

  20. Multicomponent criteria for predicting carcinogenicity: dataset of 30 NTP chemicals.

    PubMed Central

    Huff, J; Weisburger, E; Fung, V A

    1996-01-01

    This article is in response to the challenge issued to the scientific community by the National Toxicology Program to predict the carcinogenicity potential of 30 chemicals previously selected for long-term carcinogenicity testing. Utilizing the available toxicologic, genetic, and structural information on 30 chemicals previously selected for long-term carcinogenicity testing, we predict that 16 chemicals (53%) would induce some indication of carcinogenic activity in rodents; we further predict that 10 chemicals (33%) would be associated with weak or equivocal carcinogenic responses, and another 4 (13%) would give no indication of carcinogenicity. Our level of certainty is indicated for many of these predictions. Nonetheless, we believe that most instances of guessing whether a chemical would eventually induce cancer in experimental animals and hence represent a carcinogenic hazard to humans are fraught with considerable uncertainty: uncertainty that can only be relieved by long-term testing for carcinogenicity in animals or by conducting an epidemiologic investigation of exposed individuals or groups. We further believe that the day may come when our predictive acumen will be upgraded to such an extent that we might eventually obviate cancer testing. Until then, and in the best interests of public health, however, we urge long term testing of chemicals in animals be continued, at increased pace. PMID:8933061

  1. Prediction of Harmful Human Health Effects of Chemicals from Structure

    NASA Astrophysics Data System (ADS)

    Cronin, Mark T. D.

    There is a great need to assess the harmful effects of chemicals to which man is exposed. Various in silico techniques including chemical grouping and category formation, as well as the use of (Q)SARs can be applied to predict the toxicity of chemicals for a number of toxicological effects. This chapter provides an overview of the state of the art of the prediction of the harmful effects of chemicals to human health. A variety of existing data can be used to obtain information; many such data are formalized into freely available and commercial databases. (Q)SARs can be developed (as illustrated with reference to skin sensitization) for local and global data sets. In addition, chemical grouping techniques can be applied on "similar" chemicals to allow for read-across predictions. Many "expert systems" are now available that incorporate these approaches. With these in silico approaches available, the techniques to apply them successfully have become essential. Integration of different in silico approaches with each other, as well as with other alternative approaches, e.g., in vitro and -omics through the development of integrated testing strategies, will assist in the more efficient prediction of the harmful health effects of chemicals

  2. Chemical Fingerprinting of Materials Developed Due To Environmental Issues

    NASA Technical Reports Server (NTRS)

    Smith, Doris A.; McCool, A. (Technical Monitor)

    2000-01-01

    This paper presents viewgraphs on chemical fingerprinting of materials developed due to environmental issues. Some of the topics include: 1) Aerospace Materials; 2) Building Blocks of Capabilities; 3) Spectroscopic Techniques; 4) Chromatographic Techniques; 5) Factors that Determine Fingerprinting Approach; and 6) Fingerprinting: Combination of instrumental analysis methods that diagnostically characterize a material.

  3. 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...

  4. 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...

  5. ENVIRONMENTAL ANDROGENS AND ANTIANDROGENS: AN EXPANDING CHEMICAL UNIVERSE

    EPA Science Inventory

    Within the last ten years, awareness has grown about environmental chemicals that display antiandrogenic or androgenic activity. While studies in the early 1990s focused on pesticides that acted as androgen receptor (AR) antagonists, it soon became evident that this was not the ...

  6. ENVIRONMENTAL ANDROGENS AND ANTIANDROGENS: AN EXPANDING CHEMICAL UNIVERSE

    EPA Science Inventory

    Within the last ten years, awareness has grown about environmental chemicals that display antiandrogenic or androgenic activity. While studies in the early 1990s focused on pesticides that acted as androgen receptor (AR) antagonists, it soon became evident that this was not the ...

  7. High-throughput dietary exposure predictions for chemical migrants from food contact substances for use in chemical prioritization.

    PubMed

    Biryol, Derya; Nicolas, Chantel I; Wambaugh, John; Phillips, Katherine; Isaacs, Kristin

    2017-08-30

    Under the ExpoCast program, United States Environmental Protection Agency (EPA) researchers have developed a high-throughput (HT) framework for estimating aggregate exposures to chemicals from multiple pathways to support rapid prioritization of chemicals. Here, we present methods to estimate HT exposures to chemicals migrating into food from food contact substances (FCS). These methods consisted of combining an empirical model of chemical migration with estimates of daily population food intakes derived from food diaries from the National Health and Nutrition Examination Survey (NHANES). A linear regression model for migration at equilibrium was developed by fitting available migration measurements as a function of temperature, food type (i.e., fatty, aqueous, acidic, alcoholic), initial chemical concentration in the FCS (C0) and chemical properties. The most predictive variables in the resulting model were C0, molecular weight, log Kow, and food type (R(2)=0.71, p<0.0001). Migration-based concentrations for 1009 chemicals identified via publicly-available data sources as being present in polymer FCSs were predicted for 12 food groups (combinations of 3 storage temperatures and food type). The model was parameterized with screening-level estimates of C0 based on the functional role of chemicals in FCS. By combining these concentrations with daily intakes for food groups derived from NHANES, population ingestion exposures of chemical in mg/kg-bodyweight/day (mg/kg-BW/day) were estimated. Calibrated aggregate exposures were estimated for 1931 chemicals by fitting HT FCS and consumer product exposures to exposures inferred from NHANES biomonitoring (R(2)=0.61, p<0.001); both FCS and consumer product pathway exposures were significantly predictive of inferred exposures. Including the FCS pathway significantly impacted the ratio of predicted exposures to those estimated to produce steady-state blood concentrations equal to in-vitro bioactive concentrations. While these

  8. Predicting volunteer commitment in environmental stewardship programmes

    Treesearch

    Robert L. Ryan; Rachel Kaplan; Robert E. Grese

    2001-01-01

    The natural environment benefits greatly from the work of volunteers in environmental stewardship programmes. However, little is known about volunteers' motivations for continued participation in these programmes. This study looked at the relationship between volunteer commitment and motivation, as well as the effect that volunteering has on participants'...

  9. Gut Dysbiosis in Animals Due to Environmental Chemical Exposures

    PubMed Central

    Rosenfeld, Cheryl S.

    2017-01-01

    The gut microbiome consists of over 103–104 microorganism inhabitants that together possess 150 times more genes that the human genome and thus should be considered an “organ” in of itself. Such communities of bacteria are in dynamic flux and susceptible to changes in host environment and body condition. In turn, gut microbiome disturbances can affect health status of the host. Gut dysbiosis might result in obesity, diabetes, gastrointestinal, immunological, and neurobehavioral disorders. Such host diseases can originate due to shifts in microbiota favoring more pathogenic species that produce various virulence factors, such as lipopolysaccharide. Bacterial virulence factors and metabolites may be transmitted to distal target sites, including the brain. Other potential mechanisms by which gut dysbiosis can affect the host include bacterial-produced metabolites, production of hormones and factors that mimic those produced by the host, and epimutations. All animals, including humans, are exposed daily to various environmental chemicals that can influence the gut microbiome. Exposure to such chemicals might lead to downstream systemic effects that occur secondary to gut microbiome disturbances. Increasing reports have shown that environmental chemical exposures can target both host and the resident gut microbiome. In this review, we will first consider the current knowledge of how endocrine disrupting chemicals (EDCs), heavy metals, air pollution, and nanoparticles can influence the gut microbiome. The second part of the review will consider how potential environmental chemical-induced gut microbiome changes might subsequently induce pathophysiological responses in the host, although definitive evidence for such effects is still lacking. By understanding how these chemicals result in gut dysbiosis, it may open up new remediation strategies in animals, including humans, exposed to such chemicals. PMID:28936425

  10. Prediction of rodent carcinogenicity for 44 chemicals: results.

    PubMed

    Ashby, J; Tennant, R W

    1994-01-01

    Methods by which rodent carcinogenicity can be predicted have been prospectively validated for 40 chemicals evaluated for carcinogenicity by the US National Toxicology Program. It is concluded that a chemical of unknown carcinogenicity can be predicted to be in one of three possible categories--probably carcinogenic, probably non-carcinogenic or of uncertain activity. The last category is unlikely to contain genotoxic trans-species and/or multiple-site carcinogens. The component parameters of such predictions are one or more of several aspects of chemical structure, genotoxicity and rodent toxicity. Each of these parameters requires refinement but all are developed to the point that they can be integrated to make assessment of possible carcinogenicity. Carcinogenicity tends to be overpredicted by this integrated technique, each part of which has already been simulated by computer modelling. Improvements in predictive methodology will flow from three assumptions: (i) that emphasis must be placed equally on the properties of the test chemical and the responses it elicits in tissues for which carcinogenicity is to be predicted, (ii) that the integration of different predictive technique is preferable to the exclusive use of a single technique, and (iii) that the general predictivity of any technique or combination of techniques appears to be limited to < or = 80%, imposed by inadequate knowledge, and uncertainties in the experimental evaluation and classification of carcinogenic responses for diverse chemicals. This last statement does not preclude the attainment of higher accuracy within a congeneric series of chemicals. Foreknowledge of the likely outcome of a rodent carcinogenicity bioassay is now possible and will contribute to the focusing of animal testing resources.

  11. High-throughput imaging-based nephrotoxicity prediction for xenobiotics with diverse chemical structures.

    PubMed

    Su, Ran; Xiong, Sijing; Zink, Daniele; Loo, Lit-Hsin

    2016-11-01

    The kidney is a major target for xenobiotics, which include drugs, industrial chemicals, environmental toxicants and other compounds. Accurate methods for screening large numbers of potentially nephrotoxic xenobiotics with diverse chemical structures are currently not available. Here, we describe an approach for nephrotoxicity prediction that combines high-throughput imaging of cultured human renal proximal tubular cells (PTCs), quantitative phenotypic profiling, and machine learning methods. We automatically quantified 129 image-based phenotypic features, and identified chromatin and cytoskeletal features that can predict the human in vivo PTC toxicity of 44 reference compounds with ~82 % (primary PTCs) or 89 % (immortalized PTCs) test balanced accuracies. Surprisingly, our results also revealed that a DNA damage response is commonly induced by different PTC toxicants that have diverse chemical structures and injury mechanisms. Together, our results show that human nephrotoxicity can be predicted with high efficiency and accuracy by combining cell-based and computational methods that are suitable for automation.

  12. The effects of environmental chemicals on renal function

    PubMed Central

    Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

    2015-01-01

    The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease. PMID:26100504

  13. The effects of environmental chemicals on renal function.

    PubMed

    Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

    2015-10-01

    The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease.

  14. Toxic chemicals in environment and models for predicting their degradation and fate

    SciTech Connect

    Sabljic, A.

    1996-12-31

    During the last 50 years many man-made chemicals have reached every corner of the global environment despite the limitations on their use in some regions and the fact that many of them were not deliberately released into the environment. Both the mobility and persistence of commercial chemicals are the key factors for evaluating their ultimate fate and possible adverse effects on mankind and environment. The notorious global adverse effects are climate changes such as global warming, acid rain, forest decline, as well as permanent degradation of the environment and quality of life. Global and regional models have been developed for predicting transport of chemicals in atmosphere, hydrosphere, and biosphere and hence their ultimate fate or their environmental sinks. Performance of these models will be demonstrated on several classes of persistent organic chemicals. However, in order to work reliably, global and regional models for environmental fate of chemicals require, as input parameters, their physico-chemical properties and reactivity data. Unfortunately, these data are unavailable for the majority of commercial chemicals and necessary data must be calculated or estimated. The present state of the art on the calculation and estimation of several critical environmental parameters, i.e. soil sorption coefficients, tropospheric and microbiological degradation rates will be presented and evaluated including the most recent results from our laboratory.

  15. 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.

  16. Are chemicals in articles an obstacle for reaching environmental goals? - Missing links in EU chemical management.

    PubMed

    Molander, Linda; Breitholtz, Magnus; Andersson, Patrik L; Rybacka, Aleksandra; Rudén, Christina

    2012-10-01

    It is widely acknowledged that the management of risks associated with chemicals in articles needs to be improved. The EU environmental policy states that environmental damage should be rectified at source. It is therefore motivated that the risk management of substances in articles also takes particular consideration to those substances identified as posing a risk in different environmental compartments. The primary aim of the present study was to empirically analyze to what extent the regulation of chemicals in articles under REACH is coherent with the rules concerning chemicals in the Sewage Sludge Directive (SSD) and the Water Framework Directive (WFD). We also analyzed the chemical variation of the organic substances regulated under these legislations in relation to the most heavily used chemicals. The results show that 16 of 24 substances used in or potentially present in articles and regulated by the SSD or the WFD are also identified under REACH either as a substance of very high concern (SVHC) or subject to some restrictions. However, for these substances we conclude that there is limited coherence between the legislations, since the identification as an SVHC does not in itself encompass any use restrictions, and the restrictions in REACH are in many cases limited to a particular use, and thus all other uses are allowed. Only a minor part of chemicals in commerce is regulated and these show a chemical variation that deviates from classical legacy pollutants. This warrants new tools to identify potentially hazardous chemicals in articles. We also noted that chemicals monitored in the environment under the WFD deviate in their chemistry from the ones regulated by REACH. In summary, we argue that to obtain improved resource efficiency and a sustainable development it is necessary to minimize the input of chemicals identified as hazardous to health or the environment into articles. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Comparative study of biodegradability prediction of chemicals using decision trees, functional trees, and logistic regression.

    PubMed

    Chen, Guangchao; Li, Xuehua; Chen, Jingwen; Zhang, Ya-Nan; Peijnenburg, Willie J G M

    2014-12-01

    Biodegradation is the principal environmental dissipation process of chemicals. As such, it is a dominant factor determining the persistence and fate of organic chemicals in the environment, and is therefore of critical importance to chemical management and regulation. In the present study, the authors developed in silico methods assessing biodegradability based on a large heterogeneous set of 825 organic compounds, using the techniques of the C4.5 decision tree, the functional inner regression tree, and logistic regression. External validation was subsequently carried out by 2 independent test sets of 777 and 27 chemicals. As a result, the functional inner regression tree exhibited the best predictability with predictive accuracies of 81.5% and 81.0%, respectively, on the training set (825 chemicals) and test set I (777 chemicals). Performance of the developed models on the 2 test sets was subsequently compared with that of the Estimation Program Interface (EPI) Suite Biowin 5 and Biowin 6 models, which also showed a better predictability of the functional inner regression tree model. The model built in the present study exhibits a reasonable predictability compared with existing models while possessing a transparent algorithm. Interpretation of the mechanisms of biodegradation was also carried out based on the models developed.

  18. Predicting the response of populations to environmental change

    SciTech Connect

    Ives, A.R.

    1995-04-01

    When subject to long-term directional environmental perturbations, changes in population densities depend on the positive and negative feedbacks operating through interactions within and among species in a community. This paper develops techniques to predict the long-term responses of population densities to environmental changes using data on short-term population fluctuations driven by short-term environmental variability. In addition to giving quantitative predictions, the techniques also reveal how different qualitative patterns of species interactions either buffer or accentuate population responses to environmental trends. All of the predictions are based on regression coefficients extracted from time series data, and they can therefore be applied with a minimum of mathematical and statistical gymnastics. 48 refs., 10 figs., 4 tabs.

  19. Environmental chemicals impacting the thyroid: targets and consequences.

    PubMed

    Zoeller, R Thomas

    2007-09-01

    Thyroid hormone (TH) is essential for normal brain development, but the specific actions of TH differ across developmental time and brain region. These actions of TH are mediated largely by a combination of thyroid hormone receptor (TR) isoforms that exhibit specific temporal and spatial patterns of expression during animal and human brain development. In addition, TR action is influenced by different cofactors, proteins that directly link the TR protein to functional changes in gene expression. Considering the importance of TH signaling in development, it is important to consider environmental chemicals that may interfere with this signaling. Recent research indicates that environmental chemicals can interfere with thyroid function and with TH signaling. The key issues are to understand the mechanism by which these chemicals act and the dose at which they act, and whether adaptive responses intrinsic to the thyroid system can ameliorate potential adverse consequences (i.e., compensate). In addition, several recent studies show that TRs may be unintended targets of chemicals manufactured for industrial purposes to which humans and wildlife are routinely exposed. Polychlorinated biphenyls, polybrominated diphenyl ethers, bisphenol-A, and specific halogenated derivatives and metabolites of these compounds have been shown to bind to TRs and perhaps have selective effects on TR functions. A number of common chemicals, including polybrominated biphenyls and phthalates, may also exert such effects. When we consider the importance of TH in brain development, it will be important to pursue the possibilities that these chemicals-or interactions among chemical classes-are affecting children's health by influencing TH signaling in the developing brain.

  20. Integrated chemical management system: A tool for managing chemical information at the Rocky Flats Environmental Technology Site

    SciTech Connect

    Costain, D.

    1995-07-01

    The Integrated Chemical Management System is a computer-based chemical information at the Rocky Flats Environmental Technology Site. Chemical containers are identified by bar code labels and information on the type, quantity and location of chemicals are tracked on individual data bases in separate buildings. Chemical inventories from multiple buildings are uploaded to a central sitewide chemical data base where reports are available from Product, Waste, and Chemical Use modules. Hazardous chemical information is provided by a separate Material Safety Data Sheet module and excess chemicals are traded between chemical owners and users with the aid of the Chemical Exchange Module.

  1. Environmental exposure to endocrine-disrupting chemicals and miscarriage.

    PubMed

    Krieg, Sacha A; Shahine, Lora K; Lathi, Ruth B

    2016-09-15

    Establishment of early pregnancy is the result of complex biochemical interactions between the decidua and blastocyst. Any alteration in this chemical dialogue has the potential to result in adverse pregnancy outcomes including miscarriage. Sporadic miscarriage is the most common complication of pregnancy and can be caused by multiple factors. While the most common cause of miscarriage is genetic abnormalities in the fetus, other contributing factors certainly can play a role in early loss. One such factor is environmental exposure, in particular to endocrine-disrupting chemicals, which has the potential to interfere with endogenous hormone action. These effects can be deleterious, especially in early pregnancy when the hormonal milieu surrounding implantation is in delicate balance. The purpose of this paper is to review the current evidence on the role of environmental toxins in reproduction.

  2. Elucidating environmental dimensions of neurological disorders and disease: Understanding new tools from federal chemical testing programs.

    PubMed

    McPartland, Jennifer; Dantzker, Heather; Portier, Christopher

    2017-09-01

    Federal agencies are making significant investments to advance predictive approaches to evaluate chemical hazards and risks. Environmental Defense Fund (EDF) believes that engagement with the broader scientific community is critical to building and maintaining a strong biological foundation for these approaches. On June 18-19, 2015, EDF organized a meeting to 1) foster a conversation between federal scientists advancing predictive approaches and environmental health researchers investigating environmental exposures and neurological outcomes, and 2) explore opportunities and challenges for the use of federal chemical high-throughput in vitro screening (HTS) data in hypothesis-driven research toward, ultimately, improved data for public health decision-making. The meeting achieved its objectives. Government scientists showcased their chemical testing programs and vision for how emerging data may be used to meet agency missions. Environmental health researchers shared their experiences using federal HTS data, offered recommendations for strengthening federal HTS platforms, and expressed great interest in continued engagement with evolving federal chemical testing initiatives. The meeting provided an invaluable exchange between two scientific communities with a shared interest in protecting public health from harmful environmental exposures, but who have not sufficiently engaged with each other. Discussions identified opportunities and work ahead for the use of HTS data in hypothesis-driven research. Though the meeting focused on neurological outcomes, the purpose, objectives and experience of the meeting are broadly applicable. EDF strongly encourages more discourse and collaboration between federal and non-government scientists working to understand environmental influences on health outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. The Chemical Technology Division at Argonne National Laboratory: Applying chemical innovation to environmental problems

    SciTech Connect

    1995-06-01

    The Chemical Technology Division is one of the largest technical divisions at Argonne National Laboratory, a leading center for research and development related to energy and environmental issues. Since its inception in 1948, the Division has pioneered in developing separations processes for the nuclear industry. The current scope of activities includes R&D on methods for disposing of radioactive and hazardous wastes and on energy conversion processes with improved efficiencies, lower costs, and reduced environmental impact. Many of the technologies developed by CMT can be applied to solve manufacturing as well as environmental problems of industry.

  4. Evaluating the environmental hazard of industrial chemicals from data collected during the REACH registration process.

    PubMed

    Gustavsson, Mikael B; Hellohf, Andreas; Backhaus, Thomas

    2017-05-15

    Registration dossiers for 11,678 industrial chemicals were retrieved from the database of the European Chemicals Agency, of which 3566 provided a numerical entry for the corresponding predicted no effect concentration for the freshwater environment (PNEC). A distribution-based examination of 2244 of these entries reveals that the average PNEC of an industrial chemical in Europe is 238nmol/L, covering a span of 9 orders of magnitude. A comparison with biocides, pesticides, pharmaceuticals and WFD-priority pollutants reveals that, in average, industrial chemicals are least hazardous (hazard ranking: industrial chemicals≪pharmaceuticalschemicals have a lower environmental threshold than the median pesticide and 73 have a lower environmental threshold than even the median biocide. Industrial chemicals produced and/or imported in higher tonnages have, on average, higher PNECs which most likely is due to the lower assessment factors used for the PNEC determination. This pattern indicates that the initial AF of 1000 comprises a measure of conservatism. The vast majority of PNEC values are driven by EC50 and NOEC data from tests with Daphnia magna. Tests with marine species are rarely provided for the hazard characterization of industrial chemicals.

  5. NASA's Earth Science Research and Environmental Predictions

    NASA Technical Reports Server (NTRS)

    Hilsenrath, E.

    2004-01-01

    NASA Earth Science program began in the 1960s with cloud imaging satellites used for weather observations. A fleet of satellites are now in orbit to investigate the Earth Science System to uncover the connections between land, Oceans and the atmosphere. Satellite systems using an array of active and passive remote sensors are used to search for answers on how is the Earth changing and what are the consequences for life on Earth? The answer to these questions can be used for applications to serve societal needs and contribute to decision support systems for weather, hazard, and air quality predictions and mitigation of adverse effects. Partnerships with operational agencies using NASA's observational capabilities are now being explored. The system of the future will require new technology, data assimilation systems which includes data and models that will be used for forecasts that respond to user needs.

  6. NASA's Earth Science Research and Environmental Predictions

    NASA Technical Reports Server (NTRS)

    Hilsenrath, E.

    2004-01-01

    NASA Earth Science program began in the 1960s with cloud imaging satellites used for weather observations. A fleet of satellites are now in orbit to investigate the Earth Science System to uncover the connections between land, Oceans and the atmosphere. Satellite systems using an array of active and passive remote sensors are used to search for answers on how is the Earth changing and what are the consequences for life on Earth? The answer to these questions can be used for applications to serve societal needs and contribute to decision support systems for weather, hazard, and air quality predictions and mitigation of adverse effects. Partnerships with operational agencies using NASA's observational capabilities are now being explored. The system of the future will require new technology, data assimilation systems which includes data and models that will be used for forecasts that respond to user needs.

  7. Invertebrates in testing of environmental chemicals: are they alternatives?

    PubMed Central

    Lagadic, L; Caquet, T

    1998-01-01

    An enlarged interpretation of alternatives in toxicology testing includes the replacement of one animal species with another, preferably a nonmammalian species. This paper reviews the potential of invertebrates in testing environmental chemicals and provides evidence of their usefulness in alternative testing methodologies. The first part of this review addresses the use of invertebrates in laboratory toxicology testing. Problems in extrapolating results obtained in invertebrates to those obtained from vertebrates are noted, suggesting that invertebrates can essentially be used in addition to rather than as replacements for vertebrates in laboratory toxicity tests. However, evaluation of the ecologic impact of environmental chemicals must include defining end points that may frequently differ from those classically used in biomedical research. In this context, alternative approaches using invertebrates may be more pertinent. The second part of the review therefore focuses on the use of invertebrates in situ to assess the environmental impact of pollutants. Advantages of invertebrates in ecotoxicologic investigation are presented for their usefulness for seeking mechanistic links between effects occurring at the individual level and consequences for higher levels of biologic organization (e.g., population and community). In the end, it is considered that replacement of vertebrates by invertebrates in ecotoxicity testing is likely to become a reality when basic knowledge of metabolic, physiologic, and developmental patterns in the latter will be sufficient to assess the effect of a given chemical through end points that could be different between invertebrates and vertebrates. PMID:9599707

  8. Predictive performance of the Vitrigel‐eye irritancy test method using 118 chemicals

    PubMed Central

    Yamaguchi, Hiroyuki; Kojima, Hajime

    2015-01-01

    Abstract We recently developed a novel Vitrigel‐eye irritancy test (EIT) method. The Vitrigel‐EIT method is composed of two parts, i.e., the construction of a human corneal epithelium (HCE) model in a collagen vitrigel membrane chamber and the prediction of eye irritancy by analyzing the time‐dependent profile of transepithelial electrical resistance values for 3 min after exposing a chemical to the HCE model. In this study, we estimated the predictive performance of Vitrigel‐EIT method by testing a total of 118 chemicals. The category determined by the Vitrigel‐EIT method in comparison to the globally harmonized system classification revealed that the sensitivity, specificity and accuracy were 90.1%, 65.9% and 80.5%, respectively. Here, five of seven false‐negative chemicals were acidic chemicals inducing the irregular rising of transepithelial electrical resistance values. In case of eliminating the test chemical solutions showing pH 5 or lower, the sensitivity, specificity and accuracy were improved to 96.8%, 67.4% and 84.4%, respectively. Meanwhile, nine of 16 false‐positive chemicals were classified irritant by the US Environmental Protection Agency. In addition, the disappearance of ZO‐1, a tight junction‐associated protein and MUC1, a cell membrane‐spanning mucin was immunohistologically confirmed in the HCE models after exposing not only eye irritant chemicals but also false‐positive chemicals, suggesting that such false‐positive chemicals have an eye irritant potential. These data demonstrated that the Vitrigel‐EIT method could provide excellent predictive performance to judge the widespread eye irritancy, including very mild irritant chemicals. We hope that the Vitrigel‐EIT method contributes to the development of safe commodity chemicals. Copyright © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. PMID:26472347

  9. Predictive performance of the Vitrigel-eye irritancy test method using 118 chemicals.

    PubMed

    Yamaguchi, Hiroyuki; Kojima, Hajime; Takezawa, Toshiaki

    2016-08-01

    We recently developed a novel Vitrigel-eye irritancy test (EIT) method. The Vitrigel-EIT method is composed of two parts, i.e., the construction of a human corneal epithelium (HCE) model in a collagen vitrigel membrane chamber and the prediction of eye irritancy by analyzing the time-dependent profile of transepithelial electrical resistance values for 3 min after exposing a chemical to the HCE model. In this study, we estimated the predictive performance of Vitrigel-EIT method by testing a total of 118 chemicals. The category determined by the Vitrigel-EIT method in comparison to the globally harmonized system classification revealed that the sensitivity, specificity and accuracy were 90.1%, 65.9% and 80.5%, respectively. Here, five of seven false-negative chemicals were acidic chemicals inducing the irregular rising of transepithelial electrical resistance values. In case of eliminating the test chemical solutions showing pH 5 or lower, the sensitivity, specificity and accuracy were improved to 96.8%, 67.4% and 84.4%, respectively. Meanwhile, nine of 16 false-positive chemicals were classified irritant by the US Environmental Protection Agency. In addition, the disappearance of ZO-1, a tight junction-associated protein and MUC1, a cell membrane-spanning mucin was immunohistologically confirmed in the HCE models after exposing not only eye irritant chemicals but also false-positive chemicals, suggesting that such false-positive chemicals have an eye irritant potential. These data demonstrated that the Vitrigel-EIT method could provide excellent predictive performance to judge the widespread eye irritancy, including very mild irritant chemicals. We hope that the Vitrigel-EIT method contributes to the development of safe commodity chemicals. Copyright © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. Copyright © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.

  10. PEEX Modelling Platform for Seamless Environmental Prediction

    NASA Astrophysics Data System (ADS)

    Baklanov, Alexander; Mahura, Alexander; Arnold, Stephen; Makkonen, Risto; Petäjä, Tuukka; Kerminen, Veli-Matti; Lappalainen, Hanna K.; Ezau, Igor; Nuterman, Roman; Zhang, Wen; Penenko, Alexey; Gordov, Evgeny; Zilitinkevich, Sergej; Kulmala, Markku

    2017-04-01

    The Pan-Eurasian EXperiment (PEEX) is a multidisciplinary, multi-scale research programme stared in 2012 and aimed at resolving the major uncertainties in Earth System Science and global sustainability issues concerning the Arctic and boreal Northern Eurasian regions and in China. Such challenges include climate change, air quality, biodiversity loss, chemicalization, food supply, and the use of natural resources by mining, industry, energy production and transport. The research infrastructure introduces the current state of the art modeling platform and observation systems in the Pan-Eurasian region and presents the future baselines for the coherent and coordinated research infrastructures in the PEEX domain. The PEEX modeling Platform is characterized by a complex seamless integrated Earth System Modeling (ESM) approach, in combination with specific models of different processes and elements of the system, acting on different temporal and spatial scales. The ensemble approach is taken to the integration of modeling results from different models, participants and countries. PEEX utilizes the full potential of a hierarchy of models: scenario analysis, inverse modeling, and modeling based on measurement needs and processes. The models are validated and constrained by available in-situ and remote sensing data of various spatial and temporal scales using data assimilation and top-down modeling. The analyses of the anticipated large volumes of data produced by available models and sensors will be supported by a dedicated virtual research environment developed for these purposes.

  11. Approaches for predicting effects of unintended environmental ...

    EPA Pesticide Factsheets

    Tamoxifen is an endocrine-active pharmaceutical (EAP) that is used world-wide. Because tamoxifen is a ubiquitous pharmaceutical and interacts with estrogen receptors, a case study was conducted with this compound to (1) determine effects on reproductive endpoints in a nontarget species (i.e., a fish), (2) compare biologically-active metabolites across species, (3) assess whether in vitro assays predict in vivo results, and (4) investigate metabolomic profiles in tamoxifen-treated fish to better understand the biological mechanisms of tamoxifen toxicity. In reproductive assays, tamoxifen exposure caused a significant reduction in egg production and significantly increased ovarian aromatase activity in spawning adult cunner fish (Tautogolabrus adspersus). In plasma from tamoxifen-exposed cunner, the predominant metabolite was 4-hydroxytamoxifen, while in rats it was N-desmethyltamoxifen. Because 4-hydroxytamoxifen is a more biologically active metabolite than N-desmethyltamoxifen, this difference could result in a different level of risk for the two species. The results of in vitro assays with fish hepatic microsomes to assess tamoxifen metabolism did not match in vivo results, indicating probable differences in excretion of tamoxifen metabolites in fish compared with rats. For the first time, a complete in vitro characterization of the metabolism of tamoxifen using fish microsomes is presented. Furthermore, a metabolomic investigation of cunner gonad extracts dem

  12. Prediction of Rate Constants for Catalytic Reactions with Chemical Accuracy.

    PubMed

    Catlow, C Richard A

    2016-08-01

    Ex machina: A computational method for predicting rate constants for reactions within microporous zeolite catalysts with chemical accuracy has recently been reported. A key feature of this method is a stepwise QM/MM approach that allows accuracy to be achieved while using realistic models with accessible computer resources.

  13. The Formation Age of Comets: Predicted Physical and Chemical Trends

    NASA Technical Reports Server (NTRS)

    Nuth, Joesph A., III; Hill, H. G. M.

    2000-01-01

    The chemical composition of a comet has always been considered to be a function of where it formed in the nebula. We suggest that the most important factor in determining a comet's chemistry might actually be when it formed. We present specific predictions of correlations between the dust and volatile components to test our hypothesis.

  14. How well do cognitive and environmental variables predict active commuting?

    PubMed Central

    Lemieux, Mélanie; Godin, Gaston

    2009-01-01

    Background In recent years, there has been growing interest in theoretical studies integrating cognitions and environmental variables in the prediction of behaviour related to the obesity epidemic. This is the approach adopted in the present study in reference to the theory of planned behaviour. More precisely, the aim of this study was to determine the contribution of cognitive and environmental variables in the prediction of active commuting to get to and from work or school. Methods A prospective study was carried out with 130 undergraduate and graduate students (93 females; 37 males). Environmental, cognitive and socio-demographic variables were evaluated at baseline by questionnaire. Two weeks later, active commuting (walking/bicycling) to get to and from work or school was self-reported by questionnaire. Hierarchical multiple regression analyses were performed to predict intention and behaviour. Results The model predicting behaviour based on cognitive variables explained more variance than the model based on environmental variables (37.4% versus 26.8%; Z = 3.86, p < 0.001). Combining cognitive and environmental variables with socio-demographic variables to predict behaviour yielded a final model explaining 41.1% (p < 0.001) of the variance. The significant determinants were intention, habit and age. Concerning intention, the same procedure yielded a final model explaining 78.2% (p < 0.001) of the variance, with perceived behavioural control, attitude and habit being the significant determinants. Conclusion The results showed that cognitive variables play a more important role than environmental variables in predicting and explaining active commuting. When environmental variables were significant, they were mediated by cognitive variables. Therefore, individual cognitions should remain one of the main focuses of interventions promoting active commuting among undergraduate and graduate students. PMID:19267911

  15. Chemical stimulation in unconventional hydrocarbons extraction in the USA: a preliminary environmental risk assessment.

    NASA Astrophysics Data System (ADS)

    Sutra, Emilie; Spada, Matteo; Burgherr, Peter

    2016-04-01

    While the exploitation of unconventional resources recently shows an extensive development, the stimulation techniques in use in this domain arouse growing public concerns. Often in the shadow of the disputed hydraulic fracturing process, the matrix acidizing is however a complementary or alternative procedure to enhance the reservoir connectivity. Although acidizing processes are widespread within the traditional hydrocarbons sources exploration, the matrix acidizing does not appear to be commonly used in unconventional hydrocarbons formations due to their low permeability. Nonetheless, this process has been recently applied to the Monterey formation, a shale oil play in California. These stimulation fluids are composed by various chemicals, what represents a matter of concern for public as well as for authorities. As a consequence, a risk assessment implying an exposure and toxicity analysis is needed. Focusing on site surface accidents, e.g., leak of a chemical from a storage tank, we develop in this study concentration scenarios for different exposure pathways to estimate the potential environmental risk associated with the use of specific hazardous substances in the matrix acidizing process for unconventional hydrocarbon reservoirs in the USA. Primary, information about the usage of different hazardous substances have been collected in order to extract the most frequently used chemicals. Afterwards, a probabilistic estimation of the environmental risk associated with the use of these chemicals is carried out by comparing the Predicted Environmental Concentrations (PEC) distribution with the Predicted No Effect Concentrations (PNEC) value. The latter is collected from a literature review, whereas the PEC is estimated as probability distribution concentrations in different environmental compartments (e.g., soil) built upon various predefined accident scenarios. By applying a probabilistic methodology for the concentrations, the level at which the used chemicals

  16. Environmental chemical exposures and disturbances of heme synthesis.

    PubMed Central

    Daniell, W E; Stockbridge, H L; Labbe, R F; Woods, J S; Anderson, K E; Bissell, D M; Bloomer, J R; Ellefson, R D; Moore, M R; Pierach, C A; Schreiber, W E; Tefferi, A; Franklin, G M

    1997-01-01

    Porphyrias are relatively uncommon inherited or acquired disorders in which clinical manifestations are attributable to a disturbance of heme synthesis (porphyrin metabolism), usually in association with endogenous or exogenous stressors. Porphyrias are characterized by elevations of heme precursors in blood, urine, and/or stool. A number of chemicals, particularly metals and halogenated hydrocarbons, induce disturbances of heme synthesis in experimental animals. Certain chemicals have also been linked to porphyria or porphyrinuria in humans, generally involving chronic industrial exposures or environmental exposures much higher than those usually encountered. A noteworthy example is the Turkish epidemic of porphyria cutanea tarda produced by accidental ingestion of wheat treated with the fungicide hexachlorobenzene. Measurements of excreted heme precursors have the potential to serve as biological markers for harmful but preclinical effects of certain chemical exposures; this potential warrants further research and applied field studies. It has been hypothesized that several otherwise unexplained chemical-associated illnesses, such as multiple chemical sensitivity syndrome, may represent mild chronic cases of porphyria or other acquired abnormalities in heme synthesis. This review concludes that, although it is reasonable to consider such hypotheses, there is currently no convincing evidence that these illnesses are mediated by a disturbance of heme synthesis; it is premature or unfounded to base clinical management on such explanations unless laboratory data are diagnostic for porphyria. This review discusses the limitations of laboratory measures of heme synthesis, and diagnostic guidelines are provided to assist in evaluating the symptomatic individual suspected of having a porphyria. PMID:9114276

  17. Environmental management of assembled chemical weapons assessment program.

    SciTech Connect

    Frey, G.; Mohrman, G.; Templin, B. R.

    1999-05-07

    Environmental planning and management was an integral part of the ACWA Program planning process. To ensure that environmental protection issues could be addressed expeditiously and not delay the demonstrations, the PMACWA scaled the technology demonstrations such that simplified regulatory processes and existing research and development facilities could be used. The use of enclosed facilities for the demonstrations prevents any uncontrolled discharges to the environment and made it possible to conduct environmental assessments relatively quickly. The PMACWA also arranged for public briefings to ease any community concerns over the operations with chemical weapons. These steps precluded regulatory and community resistance to the ACWA activities. The cooperation of the regulators and stakeholders has been a key element in enabling the ACWA Program to move with the speed that it has to date. Technology demonstrations are currently underway and are scheduled to be completed in late May 1999. The data collected during these demonstrations will be used to prepare and submit a summary report to Congress by August 1999. The challenge continues for the ACWA management to guide the demonstrations to completion and to plan for possible pilot testing. As the scale of the ACWA facilities increase in size, the ease of reduced regulatory processes and environmental analyses will no longer be possible. However, the PMACWA will continue to explore all paths through the environmental process to speed the ACWA program to its goals while at the same time ensuring adequate protection of public health and safety and of the environment.

  18. Predicting People's Environmental Behaviour: Theory of Planned Behaviour and Model of Responsible Environmental Behaviour

    ERIC Educational Resources Information Center

    Chao, Yu-Long

    2012-01-01

    Using different measures of self-reported and other-reported environmental behaviour (EB), two important theoretical models explaining EB--Hines, Hungerford and Tomera's model of responsible environmental behaviour (REB) and Ajzen's theory of planned behaviour (TPB)--were compared regarding the fit between model and data, predictive ability,…

  19. Predicting People's Environmental Behaviour: Theory of Planned Behaviour and Model of Responsible Environmental Behaviour

    ERIC Educational Resources Information Center

    Chao, Yu-Long

    2012-01-01

    Using different measures of self-reported and other-reported environmental behaviour (EB), two important theoretical models explaining EB--Hines, Hungerford and Tomera's model of responsible environmental behaviour (REB) and Ajzen's theory of planned behaviour (TPB)--were compared regarding the fit between model and data, predictive ability,…

  20. The effect of environmental chemicals on the tumor microenvironment

    PubMed Central

    Casey, Stephanie C.; Vaccari, Monica; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Barcellos-Hoff, Mary Helen; Brown, Dustin G.; Chapellier, Marion; Christopher, Joseph; Curran, Colleen S.; Forte, Stefano; Hamid, Roslida A.; Heneberg, Petr; Koch, Daniel C.; Krishnakumar, P.K.; Laconi, Ezio; Maguer-Satta, Veronique; Marongiu, Fabio; Memeo, Lorenzo; Mondello, Chiara; Raju, Jayadev; Roman, Jesse; Roy, Rabindra; Ryan, Elizabeth P.; Ryeom, Sandra; Salem, Hosni K.; Scovassi, A.Ivana; Singh, Neetu; Soucek, Laura; Vermeulen, Louis; Whitfield, Jonathan R.; Woodrick, Jordan; Colacci, Anna Maria; Bisson, William H.; Felsher, Dean W.

    2015-01-01

    Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis. PMID:26106136

  1. The chemical biology of naphthoquinones and its environmental implications.

    PubMed

    Kumagai, Yoshito; Shinkai, Yasuhiro; Miura, Takashi; Cho, Arthur K

    2012-01-01

    Quinones are a group of highly reactive organic chemical species that interact with biological systems to promote inflammatory, anti-inflammatory, and anticancer actions and to induce toxicities. This review describes the chemistry, biochemistry, and cellular effects of 1,2- and 1,4-naphthoquinones and their derivatives. The naphthoquinones are of particular interest because of their prevalence as natural products and as environmental chemicals, present in the atmosphere as products of fuel and tobacco combustion. 1,2- and 1,4-naphthoquinones are also toxic metabolites of naphthalene, the major polynuclear aromatic hydrocarbon present in ambient air. Quinones exert their actions through two reactions: as prooxidants, reducing oxygen to reactive oxygen species; and as electrophiles, forming covalent bonds with tissue nucleophiles. The targets for these reactions include regulatory proteins such as protein tyrosine phosphatases; Kelch-like ECH-associated protein 1, the regulatory protein for NF-E2-related factor 2; and the glycolysis enzyme glyceraldehyde-3-phosphate dehydrogenase. Through their actions on regulatory proteins, quinones affect various cell signaling pathways that promote and protect against inflammatory responses and cell damage. These actions vary with the specific quinone and its concentration. Effects of exposure to naphthoquinones as environmental chemicals can vary with the physical state, i.e., whether the quinone is particle bound or is in the vapor state. The exacerbation of pulmonary diseases by air pollutants can, in part, be attributed to quinone action.

  2. The effect of environmental chemicals on the tumor microenvironment.

    PubMed

    Casey, Stephanie C; Vaccari, Monica; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Barcellos-Hoff, Mary Helen; Brown, Dustin G; Chapellier, Marion; Christopher, Joseph; Curran, Colleen S; Forte, Stefano; Hamid, Roslida A; Heneberg, Petr; Koch, Daniel C; Krishnakumar, P K; Laconi, Ezio; Maguer-Satta, Veronique; Marongiu, Fabio; Memeo, Lorenzo; Mondello, Chiara; Raju, Jayadev; Roman, Jesse; Roy, Rabindra; Ryan, Elizabeth P; Ryeom, Sandra; Salem, Hosni K; Scovassi, A Ivana; Singh, Neetu; Soucek, Laura; Vermeulen, Louis; Whitfield, Jonathan R; Woodrick, Jordan; Colacci, Annamaria; Bisson, William H; Felsher, Dean W

    2015-06-01

    Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Influence of heredity on human sensitivity to environmental chemicals

    SciTech Connect

    Weber, W.W.

    1995-12-31

    Hereditary peculiarities in individual responses to environmental chemicals are a common occurrence in human populations. Genetic variation in glutathione S-transferase, CYP1A2, N-acetyltransferase, and paraoxonase exemplify the relationship of metabolic variation to individual susceptibility to cancer and other toxicants of environmental origin. Heritable receptor protein variants, a subset of proteins of enormous pharmacogenetic, potential that have not thus far been extensively explored form the pharmacogenetic standpoint, and also considered. Examples of interest that are considered include receptor variants associated with retinoic acid resistance in acute promyelocytic leukemia, with paradoxical responses to antiandrogens in prostate cancer, and with retinitis pigmentosa. Additional heritable protein variants of pharmacogenetic interest that result in antibiotic-induced deafness, glucocorticoid-remediable aldosteronism and hypertension, the long-QT syndrome, and beryllium-induced lung disease are also discussed. These traits demonstrate how knowledge of the molecular basis and mechanism of the variant response may contribute to its prevention in sensitive persons as well as to improved therapy for genetically conditioned disorders that arise form environmental chemicals. 99 refs.

  4. Application of a predictive Bayesian model to environmental accounting.

    PubMed

    Anex, R P; Englehardt, J D

    2001-03-30

    Environmental accounting techniques are intended to capture important environmental costs and benefits that are often overlooked in standard accounting practices. Environmental accounting methods themselves often ignore or inadequately represent large but highly uncertain environmental costs and costs conditioned by specific prior events. Use of a predictive Bayesian model is demonstrated for the assessment of such highly uncertain environmental and contingent costs. The predictive Bayesian approach presented generates probability distributions for the quantity of interest (rather than parameters thereof). A spreadsheet implementation of a previously proposed predictive Bayesian model, extended to represent contingent costs, is described and used to evaluate whether a firm should undertake an accelerated phase-out of its PCB containing transformers. Variability and uncertainty (due to lack of information) in transformer accident frequency and severity are assessed simultaneously using a combination of historical accident data, engineering model-based cost estimates, and subjective judgement. Model results are compared using several different risk measures. Use of the model for incorporation of environmental risk management into a company's overall risk management strategy is discussed.

  5. Chemodynamics: transport and behavior of chemicals in the environment--a problem in environmental health.

    PubMed Central

    Freed, V H; Chiou, C T; Haque, R

    1977-01-01

    In the manufacture and use of the several thousand chemicals employed by technological societies, portions of these chemicals escape or are intentionally introduced into the environment. The behavior, fate, and to some extent the effects produced by these chemicals are a result of a complex interaction of the properties of the chemical with the various processes governing transport, degradation, sequestration, and uptake by organisms. In addition, such processes as adsorption, evaporation, partitioning, and degradation are influenced by ambient conditions of temperature, air movement, moisture, presence of other chemicals, and the concentration and properties of the subject chemicals. These influence the level and extent of exposure to these chemicals that man might receive. Study of the physiochemical properties and extent of exposure to these chem;cals that man might receive. Study of the physiochemical properties of compounds in relation to these various processes has provided a basis for better understanding of the quantitative behavior. Such information is useful in development of predictive models on behavior and fate of the chemicals in relation to human exposure. Beyond this, it provides information that could be used to devise procedures of manufacture, use, and disposal that would minimize environmental contamination. Some of the physical principles involved in chemodynamics are presented in this review. PMID:598352

  6. Predicting on-site environmental impacts of municipal engineering works

    SciTech Connect

    Gangolells, Marta Casals, Miquel Forcada, Núria Macarulla, Marcel

    2014-01-15

    The research findings fill a gap in the body of knowledge by presenting an effective way to evaluate the significance of on-site environmental impacts of municipal engineering works prior to the construction stage. First, 42 on-site environmental impacts of municipal engineering works were identified by means of a process-oriented approach. Then, 46 indicators and their corresponding significance limits were determined on the basis of a statistical analysis of 25 new-build and remodelling municipal engineering projects. In order to ensure the objectivity of the assessment process, direct and indirect indicators were always based on quantitative data from the municipal engineering project documents. Finally, two case studies were analysed and found to illustrate the practical use of the proposed model. The model highlights the significant environmental impacts of a particular municipal engineering project prior to the construction stage. Consequently, preventive actions can be planned and implemented during on-site activities. The results of the model also allow a comparison of proposed municipal engineering projects and alternatives with respect to the overall on-site environmental impact and the absolute importance of a particular environmental aspect. These findings are useful within the framework of the environmental impact assessment process, as they help to improve the identification and evaluation of on-site environmental aspects of municipal engineering works. The findings may also be of use to construction companies that are willing to implement an environmental management system or simply wish to improve on-site environmental performance in municipal engineering projects. -- Highlights: • We present a model to predict the environmental impacts of municipal engineering works. • It highlights significant on-site environmental impacts prior to the construction stage. • Findings are useful within the environmental impact assessment process. • They also

  7. Predictive remapping gives rise to environmental inhibition of return.

    PubMed

    Yan, Chuyao; He, Tao; Klein, Raymond M; Wang, Zhiguo

    2016-12-01

    Neurons in various brain regions predictively respond to stimuli that will be brought to their receptive fields by an impending eye movement. This neural mechanism, known as predictive remapping, has been suggested to underlie spatial constancy. Inhibition of return (IOR) is a bias against recently attended locations. The present study examined whether predictive remapping is a mechanism underlying IOR effects observed in environmental coordinates. The participant made saccades to a peripheral location after an IOR effect had been elicited by an onset cue and discriminated a target presented around the time of saccade onset. Immediately before the required saccade, IOR emerged at the retinal locus that would be brought to the cued location. A second task in which the participant maintained fixation during the entire trial ruled out the possibility that this IOR effect was simply the spillover of IOR from the cued location. These findings, for the first time, provide direct behavioral evidence that predictive remapping is a mechanism underlying environmental IOR.

  8. Predicting evaporation rates and times for spills of chemical mixtures.

    PubMed

    Smith, R L

    2001-08-01

    Spreadsheet and short-cut methods have been developed for predicting evaporation rates and evaporation times for spills and constrained baths of chemical mixtures. Steady-state and time-varying predictions of evaporation rates can be made for six-component mixtures, including liquid-phase non-idealities as expressed through the UNIFAC method for activity coefficients. A group-contribution method is also used to estimate vapor-phase diffusion coefficients, which makes the method completely predictive. The predictions are estimates that require professional judgement in their application. One application that the evaporation time calculations suggest is a method for labeling chemical containers that allows one to quickly assess the time for complete evaporation of spills of both pure components and mixtures. The labeling would take the form of an evaporation time that depends on the local environment. For instance, evaporation time depends on indoor or outdoor conditions and the amount of each chemical among other parameters. This labeling would provide rapid information and an opportunity to premeditate a response before a spill occurs.

  9. Predicting bioconcentration of chemicals into vegetation from soil or air using the molecular connectivity index

    SciTech Connect

    Dowdy, D.L.; McKone, T.E.; Hsieh, D.P.H.

    1995-12-31

    Bioconcentration factors (BCFs) are the ratio of chemical concentration found in an exposed organism (in this case a plant) to the concentration in an air or soil exposure medium. The authors examine here the use of molecular connectivity indices (MCIs) as quantitative structure-activity relationships (QSARS) for predicting BCFs for organic chemicals between plants and air or soil. The authors compare the reliability of the octanol-air partition coefficient (K{sub oa}) to the MC based prediction method for predicting plant/air partition coefficients. The authors also compare the reliability of the octanol/water partition coefficient (K{sub ow}) to the MC based prediction method for predicting plant/soil partition coefficients. The results here indicate that, relative to the use of K{sub ow} or K{sub oa} as predictors of BCFs the MC can substantially increase the reliability with which BCFs can be estimated. The authors find that the MC provides a relatively precise and accurate method for predicting the potential biotransfer of a chemical from environmental media into plants. In addition, the MC is much faster and more cost effective than direct measurements.

  10. 77 FR 12867 - Accreditation of ALTOL Chemical and Environmental Lab Inc., as a Commercial Laboratory

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-02

    ... SECURITY U.S. Customs and Border Protection Accreditation of ALTOL Chemical and Environmental Lab Inc., as.... ACTION: Notice of accreditation of Altol Chemical and Environmental Lab Inc., as a commercial laboratory. SUMMARY: Notice is hereby given that, pursuant to 19 CFR 151.12, Altol Chemical and Environmental Lab Inc...

  11. UK Environmental Prediction - integration and evaluation at the convective scale

    NASA Astrophysics Data System (ADS)

    Fallmann, Joachim; Lewis, Huw; Castillo, Juan Manuel; Pearson, David; Harris, Chris; Saulter, Andy; Bricheno, Lucy; Blyth, Eleanor

    2016-04-01

    It has long been understood that accurate prediction and warning of the impacts of severe weather requires an integrated approach to forecasting. For example, high impact weather is typically manifested through various interactions and feedbacks between different components of the Earth System. Damaging high winds can lead to significant damage from the large waves and storm surge along coastlines. The impact of intense rainfall can be translated through saturated soils and land surface processes, high river flows and flooding inland. The substantial impacts on individuals, businesses and infrastructure of such events indicate a pressing need to understand better the value that might be delivered through more integrated environmental prediction. To address this need, the Met Office, NERC Centre for Ecology & Hydrology and NERC National Oceanography Centre have begun to develop the foundations of a coupled high resolution probabilistic forecast system for the UK at km-scale. This links together existing model components of the atmosphere, coastal ocean, land surface and hydrology. Our initial focus has been on a 2-year Prototype project to demonstrate the UK coupled prediction concept in research mode. This presentation will provide an update on UK environmental prediction activities. We will present the results from the initial implementation of an atmosphere-land-ocean coupled system and discuss progress and initial results from further development to integrate wave interactions. We will discuss future directions and opportunities for collaboration in environmental prediction, and the challenges to realise the potential of integrated regional coupled forecasting for improving predictions and applications.

  12. [Environmental history as an anthropologic topic. Contribution to "chemical anthropology"].

    PubMed

    Grupe, G

    1990-06-01

    Human population history is firmly connected with temporal and regional changes of the environment. Whether natural or anthropogene, alteration of environmental features lead to changes of human life-style and to the development of adaptive strategies. The demand of resources for his subsistence has led man to diverse impacts on his environment since ever. Thus, environmental history is a scientific topic for anthropologists. The research potential of trace element studies of excavated human skeletons for the reconstruction of natural and socio-cultural environments as well as for distribution patterns of hazardous substances is outlined for the European Middle Ages. The scientific value of unravelling past man/environment-interrelationships for both the historical and applied sciences and the place of any "chemical anthropology" within this context is discussed.

  13. Understanding clinical immunological testing in alleged chemically induced environmental illnesses.

    PubMed

    Salvaggio, J E

    1996-08-01

    Some believe that an abnormal immunoregulatory response based on environmental damage to T cells is fundamental to the production of symptoms in patients with alleged "multiple chemical sensitivity" and/or "environmental illness." According to this theory stimulation of T cells or T cell phenotypic subsets by environmental chemicals results in release of cytokines that can effect appropriate target cells of multiple organ systems, resulting in a wide range of symptoms. This concept is reinforced by frequent media reporting of pollution incidents and environmental disasters plus continued isolated reports of immunologic abnormalities in patients with various forms of alleged environmental illness, multiple chemical sensitivities, or other related syndromes. These include reports of slight perturbations in quantity and function of immunoglobulins, complement and its components, B cells, natural killer cells, T cells, phenotypic T cell subsets, and helper suppressor T cell ratios. There are also reports of increased or decreased interleukin levels including IL-1 and IL-2 or their receptors (IL-2R) in these patients. Such assays are not infrequently performed even though there is no evidence for their diagnostic efficacy in these alleged conditions. It is reasonable, however, to anticipate that with the wide development of assays for many of the interleukins and their receptors, these assays may become important in the future diagnosis of many autoimmune, allergic, neoplastic, and infectious diseases. At this time, however, the induction of environmental illness or multiple chemical sensitivity by exposure to trace levels of environmental "immunotoxins" is unproven and remains a matter of speculation. The reproducibility of immunologic test abnormalities reported under these conditions has not been documented, and the data have often not been analyzed statistically. Appropriate controls also have not usually been employed, nor have control values been provided in many

  14. Disruption of Androgen Receptor Signaling in Males by Environmental Chemicals

    PubMed Central

    Luccio-Camelo, Doug C.; Prins, Gail S

    2011-01-01

    Androgen-disruptors are environmental chemicals in that interfere with the biosynthesis, metabolism or action of endogenous androgens resulting in a deflection from normal male developmental programming and reproductive tract growth and function. Since male sexual differentiation is entirely androgen-dependent, it is highly susceptible to androgen-disruptors. Animal models and epidemiological evidence link exposure to androgen disrupting chemicals with reduced sperm counts, increased infertility, testicular dysgenesis syndrome, and testicular and prostate cancers. Further, there appears to be increased sensitivity to these agents during critical developmental windows when male differentiation is at its peak. A variety of in vitro and in silico approaches have been used to identify broad classes of androgen disrupting molecules that include organochlorinated pesticides, industrial chemicals, and plasticizers with capacity to ligand the androgen receptor. The vast majority of these synthetic molecules act as anti-androgens. This review will highlight the evidence for androgen disrupting chemicals that act through interference with the androgen receptor, discussing specific compounds for which there is documented in vivo evidence for male reproductive tract perturbations. PMID:21515368

  15. An environmental rationale for retention of endangered chemicals

    SciTech Connect

    Wuebbles, D.J.; Calm, J.M.

    1997-11-07

    Some of the chemicals being phased out to protect the stratospheric ozone layer offer offsetting benefits such as the potential to reduce global warming. This article discusses these two environmental issues together. Six scenarios were analyzed to assess the chlorine and bromine loading of HCFC-123, raising four major policy issues: using of single measure controls places excessive emphasis on the process rather than the objectives; the current Montreal Protocol, production is tantamount to emission, warrents reconsideration; phaseout of compounds based on GWPs will not resolve global warming concerns unless related emissions of greenhouse gases are also address, and careless elimination of options can be more harmful than beneficial. 8 refs., 2 figs.

  16. From laboratory to environmental conditions: a new approach for chemical's biodegradability assessment.

    PubMed

    François, Brillet; Armand, Maul; Marie-José, Durand; Thouand, Gérald

    2016-09-01

    With thousands of organic chemicals released every day into our environment, Europe and other continents are confronted with increased risk of health and environmental problems. Even if a strict regulation such as REgistration, Authorization and restriction of CHemicals (REACH) is imposed and followed by industry to ensure that they prove the harmlessness of their substances, not all testing procedures are designed to cope with the complexity of the environment. This is especially true for the evaluation of persistence through biodegradability assessment guidelines. Our new approach has been to adapt "in the lab" biodegradability assessment to the environmental conditions and model the probability for a biodegradation test to be positive in the form of a logistic function of both the temperature and the viable cell density. Here, a proof of this new concept is proposed with the establishment of tri-dimensional biodegradability profiles of six chemicals (sodium benzoate, 4-nitrophenol, diethylene glycol, 2,4,5-trichlorophenol, atrazine, and glyphosate) between 4 to 30 °C and 10(4) to 10(8) cells ml(-1) as can be found in environmental compartments in time and space. The results show a significant increase of the predictive power of existing screening lab-scale tests designed for soluble substances. This strategy can be complementary to those current testing strategies with the creation of new indicators to quantify environmental persistence using lab-scale tests.

  17. Improving Prediction of Prostate Cancer Recurrence using Chemical Imaging

    NASA Astrophysics Data System (ADS)

    Kwak, Jin Tae; Kajdacsy-Balla, André; Macias, Virgilia; Walsh, Michael; Sinha, Saurabh; Bhargava, Rohit

    2015-03-01

    Precise Outcome prediction is crucial to providing optimal cancer care across the spectrum of solid cancers. Clinically-useful tools to predict risk of adverse events (metastases, recurrence), however, remain deficient. Here, we report an approach to predict the risk of prostate cancer recurrence, at the time of initial diagnosis, using a combination of emerging chemical imaging, a diagnostic protocol that focuses simultaneously on the tumor and its microenvironment, and data analysis of frequent patterns in molecular expression. Fourier transform infrared (FT-IR) spectroscopic imaging was employed to record the structure and molecular content from tumors prostatectomy. We analyzed data from a patient cohort that is mid-grade dominant - which is the largest cohort of patients in the modern era and in whom prognostic methods are largely ineffective. Our approach outperforms the two widely used tools, Kattan nomogram and CAPRA-S score in a head-to-head comparison for predicting risk of recurrence. Importantly, the approach provides a histologic basis to the prediction that identifies chemical and morphologic features in the tumor microenvironment that is independent of conventional clinical information, opening the door to similar advances in other solid tumors.

  18. Chemical testing strategies for predicting health hazards to children.

    PubMed

    Lamb, J C; Brown, S M

    2000-01-01

    The United States Environmental Protection Agency has proposed the development of a Children's Health Test Program under the Toxic Substances Control Act. The Environmental Protection Agency's proposal for the children's health test battery has 12 different assays including general toxicity, genotoxicity, carcinogenicity, neurotoxicity, and developmental and reproductive toxicity. The current Environmental Protection Agency testing proposal is an "all or nothing" test battery. An alternative and preferable approach would be to use a science-based, tiered testing scheme. It is proposed that the Screening Information Dataset program, currently used by the Organization for Economic Co-operation and Development (OECD) for the Screening Information Dataset-High Production Volume test battery, or equivalent, be considered for the first step. Step 1 would include acute and repeat dose toxicity testing, developmental toxicity testing (first species OECD 414 or OECD 422), reproductive toxicity screening (OECD 415 or 422), and genetic toxicity testing. For this step, the rat would be the initial and only species tested unless the mouse was used for in vivo genetic toxicity. Step 2 of the proposed children's health test battery would include developmental testing (second species OECD 414) or special mode of action studies performed for those chemicals that proved to be developmental toxicants in Step 1. Those chemicals that tested positive as reproductive toxicants in Step 1 would be tested in a two-generation reproduction study (OECD 416) or a special mode of action study. Steps 1 and 2 provide information on whether oncogenicity or developmental neurotoxicity testing is useful. Step 3 would include chronic toxicity/oncogenicity testing for those chemicals that tested positive for genetic toxicity in Step 1, and positive for developmental concerns in Step 2. In this step, chemicals would also be tested for developmental neurotoxicity if they showed evidence of neuropathy

  19. 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

  20. Environmental signaling: from environmental estrogens to endocrine-disrupting chemicals and beyond.

    PubMed

    McLachlan, J A

    2016-07-01

    The landmark report (Herbst et al. 1971) linking prenatal treatment with a synthetic estrogen, diethylstilbestrol (DES), to cancer at puberty in women whose mothers took the drug while pregnant ushered in an era of research on delayed effects of such exposures on functional outcomes in offspring. An animal model developed in our laboratory at the National Institute of Environmental Health Sciences confirmed that DES was the carcinogen and exposure to DES caused, as well, functional alterations in the reproductive, endocrine, and immune systems of male and female mice treated in utero. DES was also being used in agriculture and we discovered, at the first meeting on Estrogens in the Environment in 1979 (Estrogens in the Environment, 1980), that many environmental contaminants were also estrogenic. Many laboratories sought to discern the basis for estrogenicity in environmental chemicals and to discover other hormonally active xenobiotics. Our laboratory elucidated how DES and other estrogenic compounds worked by altering differentiation through epigenetic gene imprinting, helping explain the transgenerational effects found in mice and humans. At the Wingspread Conference on the Human-Wildlife Connection in 1991 (Advances in Modern Environmental Toxicology, 1992), we learned that environmental disruption of the endocrine system occurred in many species and phyla, and the term endocrine disruption was introduced. Further findings of transgenerational effects of environmental agents that mimicked or blocked various reproductive hormones and the ubiquity of environmental signals, such as bisphenol A increased concern for human and ecological health. Scientists began to look at other endocrine system aspects, such as cardiovascular and immune function, and other nuclear receptors, with important observations regarding obesity and metabolism. Laboratories, such as ours, are now using stem cells to try to understand the mechanisms by which various environmental signals

  1. Predicting Responses to Contemporary Environmental Change Using Evolutionary Response Architectures.

    PubMed

    Bay, Rachael A; Rose, Noah; Barrett, Rowan; Bernatchez, Louis; Ghalambor, Cameron K; Lasky, Jesse R; Brem, Rachel B; Palumbi, Stephen R; Ralph, Peter

    2017-05-01

    Rapid environmental change currently presents a major threat to global biodiversity and ecosystem functions, and understanding impacts on individual populations is critical to creating reliable predictions and mitigation plans. One emerging tool for this goal is high-throughput sequencing technology, which can now be used to scan the genome for signs of environmental selection in any species and any system. This explosion of data provides a powerful new window into the molecular mechanisms of adaptation, and although there has been some success in using genomic data to predict responses to selection in fields such as agriculture, thus far genomic data are rarely integrated into predictive frameworks of future adaptation in natural populations. Here, we review both theoretical and empirical studies of adaptation to rapid environmental change, focusing on areas where genomic data are poised to contribute to our ability to estimate species and population persistence and adaptation. We advocate for the need to study and model evolutionary response architectures, which integrate spatial information, fitness estimates, and plasticity with genetic architecture. Understanding how these factors contribute to adaptive responses is essential in efforts to predict the responses of species and ecosystems to future environmental change.

  2. Phenotypic plasticity and population viability: the importance of environmental predictability

    PubMed Central

    Reed, Thomas E.; Waples, Robin S.; Schindler, Daniel E.; Hard, Jeffrey J.; Kinnison, Michael T.

    2010-01-01

    Phenotypic plasticity plays a key role in modulating how environmental variation influences population dynamics, but we have only rudimentary understanding of how plasticity interacts with the magnitude and predictability of environmental variation to affect population dynamics and persistence. We developed a stochastic individual-based model, in which phenotypes could respond to a temporally fluctuating environmental cue and fitness depended on the match between the phenotype and a randomly fluctuating trait optimum, to assess the absolute fitness and population dynamic consequences of plasticity under different levels of environmental stochasticity and cue reliability. When cue and optimum were tightly correlated, plasticity buffered absolute fitness from environmental variability, and population size remained high and relatively invariant. In contrast, when this correlation weakened and environmental variability was high, strong plasticity reduced population size, and populations with excessively strong plasticity had substantially greater extinction probability. Given that environments might become more variable and unpredictable in the future owing to anthropogenic influences, reaction norms that evolved under historic selective regimes could imperil populations in novel or changing environmental contexts. We suggest that demographic models (e.g. population viability analyses) would benefit from a more explicit consideration of how phenotypic plasticity influences population responses to environmental change. PMID:20554553

  3. High-throughput dietary exposure predictions for chemical migrants from food contact substances for use in chemical prioritization

    EPA Science Inventory

    Under the ExpoCast program, United States Environmental Protection Agency (EPA) researchers have developed a high-throughput (HT) framework for estimating aggregate exposures to chemicals from multiple pathways to support rapid prioritization of chemicals. Here, we present method...

  4. The impact of environmental chemicals on wildlife vertebrates.

    PubMed

    Bernanke, Julia; Köhler, Heinz-R

    2009-01-01

    A plethora of papers have been published that address the affects of chemicals on wildlife vertebrates. Collectively, they support a connection between environmental pollution and effects on wildlife vertebrate populations; however, causal relationships between exposure, and reproduction or population structure effects have been established for only a few species. In a vast number of fish species, particularly in teleosts, it is accepted that EDCs affect the endocrine system of individuals and may alter sexual development and fertility. However, only few studies have demonstrated population-level consequences as a result of exposure to EDCs. The same applies to fish populations exposed to contaminants or contaminant mixtures with non-endocrine modes of action; few studies link EDCs directly to population affects. Amphibian populations are declining in many parts of the world. Although environmental chemicals have been shown to affect reproduction and development in single organism tests, the degree to which chemicals contribute to the decline of amphibians, either alone, or in concert with other factors (habitat loss, climate change, introduction of neozoa, UV-B irradiation, and direct exploitation) is still uncertain. Because reptilian endocrinology is so variable among species, EDC effects reported for individual species cannot easily be extrapolated to others. Nevertheless, for some species and locations (e.g., the Lake Popka alligators), there is considerable evidence that population declines are caused or triggered by chemical pollution. In birds, there is ample evidence for EDC effects on the reproductive system. In some bird species, effects can be linked to population declines (e.g., based on egg-shell thinning induced by DDT/DDE). In contrast, other bird species were shown to be rather insensitive to endocrine disruption. Oil spills, which also may exert endocrine effects, are usually regarded to cause only transient bird population effects, although long

  5. Modelling physico-chemical properties of (benzo)triazoles, and screening for environmental partitioning.

    PubMed

    Bhhatarai, B; Gramatica, P

    2011-01-01

    (Benzo)triazoles are distributed throughout the environment, mainly in water compartments, because of their wide use in industry where they are employed in pharmaceutical, agricultural and deicing products. They are hazardous chemicals that adversely affect humans and other non-target species, and are on the list of substances of very high concern (SVHC) in the new European regulation of chemicals - REACH (Registration, Evaluation, Authorization and Restriction of Chemical substances). Thus there is a vital need for further investigations to understand the behavior of these compounds in biota and the environment. In such a scenario, physico-chemical properties like aqueous solubility, hydrophobicity, vapor pressure and melting point can be useful. However, the limited availability and the high cost of lab testing prevents the acquisition of necessary experimental data that industry must submit for the registration of these chemicals. In such cases a preliminary analysis can be made using Quantitative Structure-Property Relationships (QSPR) models. For such an analysis, we propose Multiple Linear Regression (MLR) models based on theoretical molecular descriptors selected by Genetic Algorithm (GA). Training and prediction sets were prepared a priori by splitting the available experimental data, which were then used to derive statistically robust and predictive (both internally and externally) models. These models, after verification of their structural applicability domain (AD), were used to predict the properties of a total of 351 compounds, including those in the REACH preregistration list. Finally, Principal Component Analysis was applied to the predictions to rank the environmental partitioning properties (relevant for leaching and volatility) of new and untested (benzo)triazoles within the AD of each model. Our study using this approach highlighted compounds dangerous for the aquatic compartment. Similar analyses using predictions obtained by the EPI Suite and

  6. Environmental Impact on Vascular Development Predicted by High-Throughput Screening

    PubMed Central

    Judson, Richard S.; Reif, David M.; Sipes, Nisha S.; Singh, Amar V.; Chandler, Kelly J.; DeWoskin, Rob; Dix, David J.; Kavlock, Robert J.; Knudsen, Thomas B.

    2011-01-01

    Background: Understanding health risks to embryonic development from exposure to environmental chemicals is a significant challenge given the diverse chemical landscape and paucity of data for most of these compounds. High-throughput screening (HTS) in the U.S. Environmental Protection Agency (EPA) ToxCast™ project provides vast data on an expanding chemical library currently consisting of > 1,000 unique compounds across > 500 in vitro assays in phase I (complete) and Phase II (under way). This public data set can be used to evaluate concentration-dependent effects on many diverse biological targets and build predictive models of prototypical toxicity pathways that can aid decision making for assessments of human developmental health and disease. Objective: We mined the ToxCast phase I data set to identify signatures for potential chemical disruption of blood vessel formation and remodeling. Methods: ToxCast phase I screened 309 chemicals using 467 HTS assays across nine assay technology platforms. The assays measured direct interactions between chemicals and molecular targets (receptors, enzymes), as well as downstream effects on reporter gene activity or cellular consequences. We ranked the chemicals according to individual vascular bioactivity score and visualized the ranking using ToxPi (Toxicological Priority Index) profiles. Results: Targets in inflammatory chemokine signaling, the vascular endothelial growth factor pathway, and the plasminogen-activating system were strongly perturbed by some chemicals, and we found positive correlations with developmental effects from the U.S. EPA ToxRefDB (Toxicological Reference Database) in vivo database containing prenatal rat and rabbit guideline studies. We observed distinctly different correlative patterns for chemicals with effects in rabbits versus rats, despite derivation of in vitro signatures based on human cells and cell-free biochemical targets, implying conservation but potentially differential

  7. 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.

  8. Activation of CAR and PXR by Dietary, Environmental and Occupational Chemicals Alters Drug Metabolism, Intermediary Metabolism, and Cell Proliferation

    PubMed Central

    Hernandez, J.P.; Mota, L.C.; Baldwin, W.S.

    2010-01-01

    The constitutive androstane receptor (CAR) and the pregnane × receptor (PXR) are activated by a variety of endogenous and exogenous ligands, such as steroid hormones, bile acids, pharmaceuticals, and environmental, dietary, and occupational chemicals. In turn, they induce phase I–III detoxification enzymes and transporters that help eliminate these chemicals. Because many of the chemicals that activate CAR and PXR are environmentally-relevant (dietary and anthropogenic), studies need to address whether these chemicals or mixtures of these chemicals may increase the susceptibility to adverse drug interactions. In addition, CAR and PXR are involved in hepatic proliferation, intermediary metabolism, and protection from cholestasis. Therefore, activation of CAR and PXR may have a wide variety of implications for personalized medicine through physiological effects on metabolism and cell proliferation; some beneficial and others adverse. Identifying the chemicals that activate these promiscuous nuclear receptors and understanding how these chemicals may act in concert will help us predict adverse drug reactions (ADRs), predict cholestasis and steatosis, and regulate intermediary metabolism. This review summarizes the available data on CAR and PXR, including the environmental chemicals that activate these receptors, the genes they control, and the physiological processes that are perturbed or depend on CAR and PXR action. This knowledge contributes to a foundation that will be necessary to discern interindividual differences in the downstream biological pathways regulated by these key nuclear receptors. PMID:20871735

  9. 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.

  10. Biochar physico-chemical properties as affected by environmental exposure.

    PubMed

    Sorrenti, Giovambattista; Masiello, Caroline A; Dugan, Brandon; Toselli, Moreno

    2016-09-01

    To best use biochar as a sustainable soil management and carbon (C) sequestration technique, we must understand the effect of environmental exposure on its physical and chemical properties because they likely vary with time. These properties play an important role in biochar's environmental behavior and delivery of ecosystem services. We measured biochar before amendment and four years after amendment to a commercial nectarine orchard at rates of 5, 15 and 30tha(-1). We combined two pycnometry techniques to measure skeletal (ρs) and envelope (ρe) density and to estimate the total pore volume of biochar particles. We also examined imbibition, which can provide information about soil hydraulic conductivity. Finally, we investigated the chemical properties, surface, inner layers atomic composition and C1s bonding state of biochar fragments through X-ray photoelectron spectroscopy (XPS). Ageing increased biochar skeletal density and reduced the water imbibition rate within fragments as a consequence of partial pore clogging. However, porosity and the volume of water stored in particles remained unchanged. Exposure reduced biochar pH, EC, and total C, but enhanced total N, nitrate-N, and ammonium-N. X-ray photoelectron spectroscopy analyses showed an increase of O, Si, N, Na, Al, Ca, Mn, and Fe surface (0-5nm) atomic composition (at%) and a reduction of C and K in aged particles, confirming the interactions of biochar with soil inorganic and organic phases. Oxidation of aged biochar fragments occurred mainly in the particle surface, and progressively decreased down to 75nm. Biochar surface chemistry changes included the development of carbonyl and carboxylate functional groups, again mainly on the particle surface. However, changes were noticeable down to 75nm, while no significant changes were measured in the deepest layer, up to 110nm. Results show unequivocal shifts in biochar physical and chemical properties/characteristics over short (~years) timescales.

  11. UK Environmental Prediction - integration and evaluation at the convective scale

    NASA Astrophysics Data System (ADS)

    Fallmann, Joachim; Lewis, Huw; Castillo, Juan Manuel; Pearson, David; Harris, Chris; Saulter, Andy; Bricheno, Lucy; Blyth, Eleanor

    2016-04-01

    Traditionally, the simulation of regional ocean, wave and atmosphere components of the Earth System have been considered separately, with some information on other components provided by means of boundary or forcing conditions. More recently, the potential value of a more integrated approach, as required for global climate and Earth System prediction, for regional short-term applications has begun to gain increasing research effort. In the UK, this activity is motivated by an understanding that accurate prediction and warning of the impacts of severe weather requires an integrated approach to forecasting. The substantial impacts on individuals, businesses and infrastructure of such events indicate a pressing need to understand better the value that might be delivered through more integrated environmental prediction. To address this need, the Met Office, NERC Centre for Ecology & Hydrology and NERC National Oceanography Centre have begun to develop the foundations of a coupled high resolution probabilistic forecast system for the UK at km-scale. This links together existing model components of the atmosphere, coastal ocean, land surface and hydrology. Our initial focus has been on a 2-year Prototype project to demonstrate the UK coupled prediction concept in research mode. This presentation will provide an update on UK environmental prediction activities. We will present the results from the initial implementation of an atmosphere-land-ocean coupled system, including a new eddy-permitting resolution ocean component, and discuss progress and initial results from further development to integrate wave interactions in this relatively high resolution system. We will discuss future directions and opportunities for collaboration in environmental prediction, and the challenges to realise the potential of integrated regional coupled forecasting for improving predictions and applications.

  12. Integrated strategy for mutagenicity prediction applied to food contact chemicals.

    PubMed

    Manganelli, Serena; Schilter, Benoît; Benfenati, Emilio; Manganaro, Alberto; Lo Piparo, Elena

    2017-09-18

    Food contamination due to unintentional leakage of chemicals from food contact materials (FCM) is a source of increasing concern. Since for many of these substances, only limited or no toxicological data are available, the development of alternative methodologies to establish rapidly and cost-efficiently level of safety concern is critical to ensure adequate consumer protection. Computational toxicology methods are considered the most promising solutions to cope with this data gap. In particular, mutagenicity assessment has a particular relevance and is a mandatory requirement for all substances released from plastic FCM, regardless how low migration and exposure are. In the present work, a strategy integrating a number of (Quantitative) Structure Activity Relationship ((Q)SAR) models for Ames mutagenicity predictions is proposed. A list of chemicals representing likely migrating moieties from FCM was selected to test the value of the newly defined strategy and the possibility to combine predictions given by the different algorithms was evaluated. In particular, a scheme to integrate mutagenicity estimations into a single final assessment was developed resulting in an increased domain of applicability. In most cases, a deeper analysis of experimental data, where available, allowed fixing misclassification errors, highlighting the importance of data curation in the development, validation and application of in silico methods. The high accuracy of the strategy provided the rationales for its application for toxicologically uncharacterized chemicals. Finally, the overall strategy of integration will be automated through its implementation into a freely available software application.

  13. Predictions of Chemical Weather in Asia: The EU Panda Project

    NASA Astrophysics Data System (ADS)

    Brasseur, G. P.; Petersen, A. K.; Wang, X.; Granier, C.; Bouarar, I.

    2014-12-01

    Air quality has become a pressing problem in Asia and specifically in China due to rapid economic development (i.e., rapidly expanding motor vehicle fleets, growing industrial and power generation activities, domestic and biomass burning). In spite of efforts to reduce chemical emissions, high levels of particle matter and ozone are observed and lead to severe health problems with a large number of premature deaths. To support efforts to reduce air pollution, the European Union is supporting the PANDA project whose objective is to use space and surface observations of chemical species as well as advanced meteorological and chemical models to analyze and predict air quality in China. The Project involves 7 European and 7 Chinese groups. The paper will describe the objectives of the project and present some first accomplishments. The project focuses on the improvement of methods for monitoring air quality from combined space and in-situ observations, the development of a comprehensive prediction system that makes use of these observations, the elaboration of indicators for air quality in support of policies, and the development of toolboxes for the dissemination of information.

  14. 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.

  15. Fate of sessile droplet chemical agents in environmental substrates in the presence of physiochemical processes

    NASA Astrophysics Data System (ADS)

    Navaz, H. K.; Dang, A. L.; Atkinson, T.; Zand, A.; Nowakowski, A.; Kamensky, K.

    2014-05-01

    A general-purpose multi-phase and multi-component computer model capable of solving the complex problems encountered in the agent substrate interaction is developed. The model solves the transient and time-accurate mass and momentum governing equations in a three dimensional space. The provisions for considering all the inter-phase activities (solidification, evaporation, condensation, etc.) are included in the model. The chemical reactions among all phases are allowed and the products of the existing chemical reactions in all three phases are possible. The impact of chemical reaction products on the transport properties in porous media such as porosity, capillary pressure, and permeability is considered. Numerous validations for simulants, agents, and pesticides with laboratory and open air data are presented. Results for chemical reactions in the presence of pre-existing water in porous materials such as moisture, or separated agent and water droplets on porous substrates are presented. The model will greatly enhance the capabilities in predicting the level of threat after any chemical such as Toxic Industrial Chemicals (TICs) and Toxic Industrial Materials (TIMs) release on environmental substrates. The model's generality makes it suitable for both defense and pharmaceutical applications.

  16. Simultaneous prediction of enzyme orthologs from chemical transformation patterns for de novo metabolic pathway reconstruction

    PubMed Central

    Tabei, Yasuo; Yamanishi, Yoshihiro; Kotera, Masaaki

    2016-01-01

    Motivation: Metabolic pathways are an important class of molecular networks consisting of compounds, enzymes and their interactions. The understanding of global metabolic pathways is extremely important for various applications in ecology and pharmacology. However, large parts of metabolic pathways remain unknown, and most organism-specific pathways contain many missing enzymes. Results: In this study we propose a novel method to predict the enzyme orthologs that catalyze the putative reactions to facilitate the de novo reconstruction of metabolic pathways from metabolome-scale compound sets. The algorithm detects the chemical transformation patterns of substrate–product pairs using chemical graph alignments, and constructs a set of enzyme-specific classifiers to simultaneously predict all the enzyme orthologs that could catalyze the putative reactions of the substrate–product pairs in the joint learning framework. The originality of the method lies in its ability to make predictions for thousands of enzyme orthologs simultaneously, as well as its extraction of enzyme-specific chemical transformation patterns of substrate–product pairs. We demonstrate the usefulness of the proposed method by applying it to some ten thousands of metabolic compounds, and analyze the extracted chemical transformation patterns that provide insights into the characteristics and specificities of enzymes. The proposed method will open the door to both primary (central) and secondary metabolism in genomics research, increasing research productivity to tackle a wide variety of environmental and public health matters. Availability and Implementation: Contact: maskot@bio.titech.ac.jp PMID:27307627

  17. Modelling Chemical Reasoning to Predict and Invent Reactions.

    PubMed

    Segler, Marwin H S; Waller, Mark P

    2016-11-11

    The ability to reason beyond established knowledge allows organic chemists to solve synthetic problems and invent novel transformations. Herein, we propose a model that mimics chemical reasoning, and formalises reaction prediction as finding missing links in a knowledge graph. We have constructed a knowledge graph containing 14.4 million molecules and 8.2 million binary reactions, which represents the bulk of all chemical reactions ever published in the scientific literature. Our model outperforms a rule-based expert system in the reaction prediction task for 180 000 randomly selected binary reactions. The data-driven model generalises even beyond known reaction types, and is thus capable of effectively (re-)discovering novel transformations (even including transition metal-catalysed reactions). Our model enables computers to infer hypotheses about reactivity and reactions by only considering the intrinsic local structure of the graph and because each single reaction prediction is typically achieved in a sub-second time frame, the model can be used as a high-throughput generator of reaction hypotheses for reaction discovery.

  18. Prediction of odor from pig production based on chemical odorants.

    PubMed

    Hansen, Michael J; Adamsen, Anders Peter S; Pedersen, Poul; Feilberg, Anders

    2012-01-01

    The present work was performed to investigate the use of odorant measurements for prediction of odor concentration in facilities with growing-finishing pigs and to analyze the odorant composition in facilities with different floor and ventilation systems. Air was sampled in Nalophan bags, odor concentrations were measured by dilution-to-threshold olfactometry, and concentrations of odorants were measured by proton-transfer-reaction mass spectrometry (PTR-MS). Olfactometry and chemical analyses were synchronized to take place at identical time intervals after sampling. A principal component analysis revealed that different facilities for growing-finishing pigs can be distinguished based on the odorants. Pit ventilation comprising a small amount of the total ventilation air (10-20%) in facilities with both room and pit ventilation can be used to concentrate odorants, whereas the room ventilation contains lower concentrations of most odorants. A partial least squares regression model demonstrated that prediction of the odor concentration based on odorants measured by PTR-MS is feasible. Hydrogen sulfide, methanethiol, trimethylamine, and 4-methylphenol were identified as the compounds having the largest influence on the prediction of odor concentration, whereas carboxylic acids had no significant influence. In conclusion, chemical measurement of odorants by PTR-MS is an alternative for expressing the odor concentration in facilities with growing-finishing pigs that can be used to increase the understanding of odor from different types of facilities and improve the development of odor reduction technologies.

  19. CHEMICAL HAZARD EVALUATION FOR MANAGEMENT STRATEGIES: A METHOD FOR RANKING AND SCORING CHEMICALS BY POTENTIAL HUMAN HEALTH AND ENVIRONMENTAL IMPACTS

    EPA Science Inventory

    Between 60,000 and 100,000 of the over than 8,000,000 chemicals listed by the Chemical Abstracts Services Registry are commercially produced and are potential environmental pollutants. Risk-based evaluation for these chemicals is often required to evaluate the potential impacts...

  20. CHEMICAL HAZARD EVALUATION FOR MANAGEMENT STRATEGIES: A METHOD FOR RANKING AND SCORING CHEMICALS BY POTENTIAL HUMAN HEALTH AND ENVIRONMENTAL IMPACTS

    EPA Science Inventory

    Between 60,000 and 100,000 of the over than 8,000,000 chemicals listed by the Chemical Abstracts Services Registry are commercially produced and are potential environmental pollutants. Risk-based evaluation for these chemicals is often required to evaluate the potential impacts...

  1. Developing predictions of in vivo developmental toxicity of ToxCast chemicals using mouse embryonic stem cells.

    EPA Science Inventory

    Developing predictions of in vivo developmental toxicity of ToxCast chemicals using mouse embryonic stem cells S. Hunter, M. Rosen, M. Hoopes, H. Nichols, S. Jeffay, K. Chandler1, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Labor...

  2. Developing predictions of in vivo developmental toxicity of ToxCast chemicals using mouse embryonic stem cells.

    EPA Science Inventory

    Developing predictions of in vivo developmental toxicity of ToxCast chemicals using mouse embryonic stem cells S. Hunter, M. Rosen, M. Hoopes, H. Nichols, S. Jeffay, K. Chandler1, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Labor...

  3. Andra Environmental Specimen Bank: archiving the environmental chemical quality for long-term monitoring.

    PubMed

    Leclerc, Elisabeth; d'Arbaumont, Maëlle; Verron, Jean-Patrick; Goldstein, Céline; Cesar, Frédérique; Dewonck, Sarah

    2015-02-01

    Andra Environmental Specimen Bank (ESB) was established in 2010 as a part of the Perennial Observatory of the Environment (OPE), ongoing Long-Term Environmental Research Monitoring and Testing System located next to the Underground Research Laboratory (URL) at Bure, Meuse/Haute-Marne, France. The URL is used to study the deep geological disposal of high and intermediate level radioactive waste. Andra ESB is designed to archive during at least 100 years samples collected to define the initial state of environmental quality of the local area before the construction of industrial facilities and to ensure the traceability of long-term series of samples collected by the OPE ( http://www.andra.fr/ope ), using safe long-term conservation practices. Samples archived in the bank include some local food chain products (milk, cheese, honey, cereals, grass, cherry plum…) and specimen usually archived internationally to monitor the environmental quality (soil, sediment, water, fish, tree leaves, wild life, etc.). Regarding the different samples and analytical issues, three conservation modalities and facilities were designed: dry conservation under controlled temperature and humidity, cryopreservation in liquid nitrogen (LN2) vapor phase freezers (-150 °C) and in deep-freezing at -80 °C for temporary storage and raw samples before preparation. Andra ESB is equipped with a sample preparation clean room, certified ISO Class 5, dedicated to cryopreservation. This paper describes this first French experiment of long-term chemical quality monitoring and samples cryopreservation of different ecosystems and environmental compartments.

  4. Animals as sentinels of human health hazards of environmental chemicals.

    PubMed Central

    van der Schalie, W H; Gardner, H S; Bantle, J A; De Rosa, C T; Finch, R A; Reif, J S; Reuter, R H; Backer, L C; Burger, J; Folmar, L C; Stokes, W S

    1999-01-01

    A workshop titled "Using Sentinel Species Data to Address the Potential Human Health Effects of Chemicals in the Environment," sponsored by the U.S. Army Center for Environmental Health Research, the National Center for Environmental Assessment of the EPA, and the Agency for Toxic Substances and Disease Registry, was held to consider the use of sentinel and surrogate animal species data for evaluating the potential human health effects of chemicals in the environment. The workshop took a broad view of the sentinel species concept, and included mammalian and nonmammalian species, companion animals, food animals, fish, amphibians, and other wildlife. Sentinel species data included observations of wild animals in field situations as well as experimental animal data. Workshop participants identified potential applications for sentinel species data derived from monitoring programs or serendipitous observations and explored the potential use of such information in human health hazard and risk assessments and for evaluating causes or mechanisms of effect. Although it is unlikely that sentinel species data will be used as the sole determinative factor in evaluating human health concerns, such data can be useful as for additional weight of evidence in a risk assessment, for providing early warning of situations requiring further study, or for monitoring the course of remedial activities. Attention was given to the factors impeding the application of sentinel species approaches and their acceptance in the scientific and regulatory communities. Workshop participants identified a number of critical research needs and opportunities for interagency collaboration that could help advance the use of sentinel species approaches. PMID:10090711

  5. Development and Validation of Decision Forest Model for Estrogen Receptor Binding Prediction of Chemicals Using Large Data Sets.

    PubMed

    Ng, Hui Wen; Doughty, Stephen W; Luo, Heng; Ye, Hao; Ge, Weigong; Tong, Weida; Hong, Huixiao

    2015-12-21

    Some chemicals in the environment possess the potential to interact with the endocrine system in the human body. Multiple receptors are involved in the endocrine system; estrogen receptor α (ERα) plays very important roles in endocrine activity and is the most studied receptor. Understanding and predicting estrogenic activity of chemicals facilitates the evaluation of their endocrine activity. Hence, we have developed a decision forest classification model to predict chemical binding to ERα using a large training data set of 3308 chemicals obtained from the U.S. Food and Drug Administration's Estrogenic Activity Database. We tested the model using cross validations and external data sets of 1641 chemicals obtained from the U.S. Environmental Protection Agency's ToxCast project. The model showed good performance in both internal (92% accuracy) and external validations (∼ 70-89% relative balanced accuracies), where the latter involved the validations of the model across different ER pathway-related assays in ToxCast. The important features that contribute to the prediction ability of the model were identified through informative descriptor analysis and were related to current knowledge of ER binding. Prediction confidence analysis revealed that the model had both high prediction confidence and accuracy for most predicted chemicals. The results demonstrated that the model constructed based on the large training data set is more accurate and robust for predicting ER binding of chemicals than the published models that have been developed using much smaller data sets. The model could be useful for the evaluation of ERα-mediated endocrine activity potential of environmental chemicals.

  6. Potential of environmental models to predict meningitis epidemics in Africa.

    PubMed

    Thomson, Madeleine C; Molesworth, Anna M; Djingarey, Mamoudou H; Yameogo, K R; Belanger, Francois; Cuevas, Luis E

    2006-06-01

    Meningococcal meningitis is a major public health problem in Africa. This report explores the potential for climate/environmental models to predict the probability of occurrence of meningitis epidemics. Time series of meningitis cases by month and district were obtained for Burkina Faso, Niger, Mali and Togo (536 district-years). Environmental information (1989-1999) for the continent [soil and land-cover type, aerosol index, vegetation greenness (NDVI), cold cloud duration (CCD) and rainfall] was used to develop models to predict the incidence of meningitis. Meningitis incidence, dust, rainfall, NDVI and CCD were analysed as anomalies (mean minus observed value). The models were developed using univariate and stepwise multi-variate linear regression. Anomalies in annual meningitis incidence at district level were related to monthly climate anomalies. Significant relationships were found for both estimates of rainfall and dust in the pre-, post- and epidemic season. While present in all land-cover classes these relationships were strongest in savannah areas. Predicting epidemics of meningitis could be feasible. To fully develop this potential, we require (a) a better understanding of the epidemiological and environmental phenomena underpinning epidemics and how satellite derived climate proxies reflect conditions on the ground and (b) more extensive epidemiological and environmental datasets. Climate forecasting tools capable of predicting climate variables 3-6 months in advance of an epidemic would increase the lead-time available for control strategies. Our increased capacity for data processing; the recent improvements in meningitis surveillance in preparation for the distribution of the impending conjugate vaccines and the development of other early warning systems for epidemic diseases in Africa, favours the creation of these models.

  7. Predictive spectroscopy and chemical imaging based on novel optical systems

    NASA Astrophysics Data System (ADS)

    Nelson, Matthew Paul

    1998-10-01

    This thesis describes two futuristic optical systems designed to surpass contemporary spectroscopic methods for predictive spectroscopy and chemical imaging. These systems are advantageous to current techniques in a number of ways including lower cost, enhanced portability, shorter analysis time, and improved S/N. First, a novel optical approach to predicting chemical and physical properties based on principal component analysis (PCA) is proposed and evaluated. A regression vector produced by PCA is designed into the structure of a set of paired optical filters. Light passing through the paired filters produces an analog detector signal directly proportional to the chemical/physical property for which the regression vector was designed. Second, a novel optical system is described which takes a single-shot approach to chemical imaging with high spectroscopic resolution using a dimension-reduction fiber-optic array. Images are focused onto a two- dimensional matrix of optical fibers which are drawn into a linear distal array with specific ordering. The distal end is imaged with a spectrograph equipped with an ICCD camera for spectral analysis. Software is used to extract the spatial/spectral information contained in the ICCD images and deconvolute them into wave length-specific reconstructed images or position-specific spectra which span a multi-wavelength space. This thesis includes a description of the fabrication of two dimension-reduction arrays as well as an evaluation of the system for spatial and spectral resolution, throughput, image brightness, resolving power, depth of focus, and channel cross-talk. PCA is performed on the images by treating rows of the ICCD images as spectra and plotting the scores of each PC as a function of reconstruction position. In addition, iterative target transformation factor analysis (ITTFA) is performed on the spectroscopic images to generate ``true'' chemical maps of samples. Univariate zero-order images, univariate first

  8. Predicting regional lung deposition of environmental tobacco smoke particles

    SciTech Connect

    Nazaroff, W.W.; Hung, W.Y.; Sasse, A.G.B.M.; Gadgil, A.J.

    1993-10-01

    Inhalation exposure of environmental tobacco smoke (ETS) particles may increase health risks, but only to the extent that the particles deposit in the respiratory tract. We describe a technique to predict regional lung deposition of environmental tobacco smoke particles. Interpretation of particle size distribution measurements after cigarette combustion by a smoking machine in a test room yields an effective emissions profile. An aerosol dynamics model is used to predict indoor particle concentrations resulting from a specified combination of smoking frequency and building factors. By utilizing a lung deposition model, the rate of ETS mass accumulation in human lungs is then determined as a function of particle size and lung airway generation. Considering emissions of sidestream smoke only, residential exposures of nonsmokers to ETS are predicted to cause rates of total respiratory tract particle deposition in the range of 0.4-0.7 {mu}g/day per kg of body weight for light smoking in a well-ventilated residence and 8-13 {mu}g/day per kg for moderately heavy smoking in a poorly ventilated residence. Emissions of sidestream plus mainstream smoke lead to predicted deposition rates about a factor of 4 higher. This technique should be useful for evaluating health risks and control techniques associated with exposure to ETS particles. 36 refs., 6 figs., 3 tabs.

  9. Predicting co-morbidities in chemically sensitive individuals from exhaled breath analysis.

    PubMed

    Zeliger, Harold I; Pan, Yaqin; Rea, William J

    2012-09-01

    The exhaled breath of more than four hundred patients who presented at the Environmental Health Center - Dallas with chemical sensitivity conditions were analyzed for the relative abundance of their breath chemical composition by gas chromatography and mass spectrometry for volatile and semi-volatile organic compounds. All presenting patients had no fewer than four and as many as eight co-morbid conditions. Surprisingly, almost all the exhaled breath analyses showed the presence of a preponderance of lipophilic aliphatic and aromatic hydrocarbons. The hydrophilic compounds present were almost entirely of natural origin, i.e. expected metabolites of foods. The lipophile, primarily C3 to C16 hydrocarbons and believed to have come from inhalation of polluted air, were, in all cases, present at concentrations far below those known to be toxic to humans, but caused sensitivity and signs of chemical overload. The co-morbid health effects observed are believed to be caused by the sequential absorption of lipophilic and hydrophilic chemicals; an initial absorption and retention of lipophile followed by a subsequent absorption of hydrophilic species facilitated by the retained lipophile to produce chemical mixtures that are toxic at very low levels. It is hypothesized that co-morbid conditions in chemically sensitive individuals can be predicted from analysis of their exhaled breath.

  10. [Development of Chemical Exposure Prediction Model for Aerobic Sewage Treatment Plant for Biochemical Wastewaters].

    PubMed

    Zhou, Lin-jun; Liu, Ji-ning; Shi, Li-li; Feng, Jie; Xu, Yan-hua

    2016-01-15

    Sewage treatment plant (STP) is a key transfer station for chemicals distributed into different environment compartment, and hence models of exposure prediction play a crucial role in the environmental risk assessment and pollution prevention of chemicals. A mass balance model namely Chinese Sewage treatment plant (C-STP(O)) was developed to predict the fate and exposure of chemicals in a conventional sewage treatment plant. The model was expressed as 9 mixed boxes by compartment of air, water, suspended solids, and settled solids. It was based on the minimum input data required on the notification in new chemicals, such as molecular weight, absorption coefficient, vapor pressure, water solubility, ready or inherent biodegradability. The environment conditions ( Temperature = 283 K, wind speed = 2 m x s(-1)) and the classic STP scenario parameters of China, especially the scenario parameters of water quality and sludge properties were adopted in C-STP( 0) model to reflect Chinese characteristics, these parameters were sewage flow of 35 000 m3 x d(-1), influent BOD5 of 0.15 g x L(-1), influent SS of 0.2 kg x m(-3), effluent SS of 0.02 kg x m(-3), BOD5 removal in aerator of 90% sludge density of 1.6 kg x L(3) and organic carbon content of 0.18-0.19. It adopted the fugacity express for mechanism of linear absorption, first-order degradation, Whitman two resistances. An overall interphase transfer constant which was the sum of surface volatilization and stripping was used to assess the volatilization in aerator. The most important and uncertain input value was the biodegradation rate constant, and determination of which required a tier test strategy from ready or inherent biodegradability data to simulate test in STP. An extrapolated criterion of US EPA to derive biodegradation rate constant using the results of ready and inherent biodegradability was compared with that of EU and was recommended. C-STP ( 0 ) was valid to predict the relative emission of volatilization

  11. Predicting Chemical Environments of Bacteria from Receptor Signaling

    PubMed Central

    Neumann, Silke; Sourjik, Victor; Endres, Robert G.

    2014-01-01

    Sensory systems have evolved to respond to input stimuli of certain statistical properties, and to reliably transmit this information through biochemical pathways. Hence, for an experimentally well-characterized sensory system, one ought to be able to extract valuable information about the statistics of the stimuli. Based on dose-response curves from in vivo fluorescence resonance energy transfer (FRET) experiments of the bacterial chemotaxis sensory system, we predict the chemical gradients chemotactic Escherichia coli cells typically encounter in their natural environment. To predict average gradients cells experience, we revaluate the phenomenological Weber's law and its generalizations to the Weber-Fechner law and fold-change detection. To obtain full distributions of gradients we use information theory and simulations, considering limitations of information transmission from both cell-external and internal noise. We identify broad distributions of exponential gradients, which lead to log-normal stimuli and maximal drift velocity. Our results thus provide a first step towards deciphering the chemical nature of complex, experimentally inaccessible cellular microenvironments, such as the human intestine. PMID:25340783

  12. Study of improved methods for predicting chemical equilibria

    NASA Astrophysics Data System (ADS)

    Lenz, Terry G.; Vaughan, John D.

    The research involves developing general computational methods for predicting the thermodynamic properties of condensed state chemically reactive systems. The overall effort has encompassed both computer studies, and parallel laboratory experimental work to support the evolving computational models. To date, the soundness of molecular mechanics/force-field techniques were demonstrated for accurate prediction of the thermodynamic properties of chemically reactive systems. Extensive work was done with three molecular mechanics models, Boyd's MOLBD3, Allinger's MMP2 and the Warshel/Lifson/Karplus QCFF/PI program. Not one of these programs at present has general full thermodynamic output capability. Modification of the QCFF/PI is well on its way to full thermodynamic capability. Supporting laboratory studies have involved careful bomb calorimetry for H(sub f) information, X-ray structure determination for accurate molecular geometry data, and kinetics/equilibrium determinations for various prototypical Diels-Alder reactions. Vapor pressure studies for candidate Diels-Alder compounds are also underway. The bomb calorimetric and greater initial effort on vapor pressure studies have replaced the original solvent effect and hindered rotation NMR studies planned, on the basis of most critical data needs for correct computational model development.

  13. Environmental sensing and response genes in Cnidaria: the chemical defensome in the sea anemone Nematostella vectensis

    PubMed Central

    Goldstone, J.V.

    2010-01-01

    The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of the bilateria. Cnidaria play important roles in estuarine and reef communities, but are exposed to many environmental stressors. Here I describe the genetic components of a ‘chemical defensome’ in the genome of N. vectensis, and review cnidarian molecular toxicology. Gene families that defend against chemical stressors and the transcription factors that regulate these genes have been termed a ‘chemical defensome,’ and include the cytochromes P450 and other oxidases, various conjugating enyzymes, the ATP-dependent efflux transporters, oxidative detoxification proteins, as well as various transcription factors. These genes account for about 1% (266/27200) of the predicted genes in the sea anemone genome, similar to the proportion observed in tunicates and humans, but lower than that observed in sea urchins. While there are comparable numbers of stress-response genes, the stress sensor genes appear to be reduced in N. vectensis relative to many model protostomes and deuterostomes. Cnidarian toxicology is understudied, especially given the important ecological roles of many cnidarian species. New genomic resources should stimulate the study of chemical stress sensing and response mechanisms in cnidaria, and allow us to further illuminate the evolution of chemical defense gene networks. PMID:18956243

  14. Environmental sensing and response genes in cnidaria: the chemical defensome in the sea anemone Nematostella vectensis.

    PubMed

    Goldstone, J V

    2008-12-01

    The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of the bilateria. Cnidaria play important roles in estuarine and reef communities, but are exposed to many environmental stressors. Here, I describe the genetic components of a "chemical defensome" in the genome of N. vectensis and review cnidarian molecular toxicology. Gene families that defend against chemical stressors and the transcription factors that regulate these genes have been termed a chemical defensome and include the cytochromes P450 and other oxidases, various conjugating enyzymes, the ATP-dependent efflux transporters, oxidative detoxification proteins, as well as various transcription factors. These genes account for about 1% (266/27,200) of the predicted genes in the sea anemone genome, similar to the proportion observed in tunicates and humans, but lower than that observed in sea urchins. While there are comparable numbers of stress-response genes, the stress sensor genes appear to be reduced in N. vectensis relative to many model protostomes and deuterostomes. Cnidarian toxicology is understudied, especially given the important ecological roles of many cnidarian species. New genomic resources should stimulate the study of chemical stress sensing and response mechanisms in cnidaria and allow us to further illuminate the evolution of chemical defense gene networks.

  15. Evaluation of artificial intelligence based models for chemical biodegradability prediction.

    PubMed

    Baker, James R; Gamberger, Dragan; Mihelcic, James R; Sabljić, Aleksandar

    2004-12-31

    This study presents a review of biodegradability modeling efforts including a detailed assessment of two models developed using an artificial intelligence based methodology. Validation results for these models using an independent, quality reviewed database, demonstrate that the models perform well when compared to another commonly used biodegradability model, against the same data. The ability of models induced by an artificial intelligence methodology to accommodate complex interactions in detailed systems, and the demonstrated reliability of the approach evaluated by this study, indicate that the methodology may have application in broadening the scope of biodegradability models. Given adequate data for biodegradability of chemicals under environmental conditions, this may allow for the development of future models that include such things as surface interface impacts on biodegradability for example.

  16. Consensus models to predict endocrine disruption for all human-exposure chemicals (AAAS Annual Meeting)

    EPA Science Inventory

    Humans are potentially exposed to tens of thousands of man-made chemicals in the environment. It is well known that some environmental chemicals mimic natural hormones and thus have the potential to be endocrine disruptors. Most of these environmental chemicals have never been te...

  17. Environmental Impact Research Program: Environmental Impact Assessment in Coastal Habitats: An Evaluation of Predictions

    DTIC Science & Technology

    1990-09-01

    Charleston Harbor deepening project, Charleston Harbor and Shipyard River , 1976 NAV South Carolina Maintenance dredging of Atlantic intracoastal waterway... South Carolina 1976 NAV Hunting Island Beach, South Carolina 1975 SP Application by AMOCO Chemicals Corp. for a permit to dredge in the Cooper River ...Neches River at Beaumont, TX 1975 MIS Portland District Umpqua River jetty extension 1976/77 NAV Columbia and Lower Willamette River environmental

  18. Toxic Environmental Chemicals: The Role of Reproductive Health Professionals In Preventing Harmful Exposures

    PubMed Central

    SUTTON, Patrice; WOODRUFF, Tracey J.; PERRON, Joanne; STOTLAND, Naomi; CONRY, Jeanne A.; MILLER, Mark D.; GIUDICE, Linda C.

    2015-01-01

    Every pregnant woman in the U.S. is exposed to many and varied environmental chemicals. Rapidly accumulating scientific evidence documents that widespread exposure to environmental chemicals at levels encountered in daily life can adversely impact reproductive and developmental health. Preconception and prenatal exposure to environmental chemicals are of particular import because they may have a profound and lasting impact on health across the life course. Thus, preventing developmental exposures to environmental chemicals would benefit greatly from the active participation of reproductive health professionals in clinical and policy arenas. PMID:22405527

  19. UK Environmental Prediction - integration and evaluation at the convective scale

    NASA Astrophysics Data System (ADS)

    Lewis, Huw; Brunet, Gilbert; Harris, Chris; Best, Martin; Saulter, Andrew; Holt, Jason; Bricheno, Lucy; Brerton, Ashley; Reynard, Nick; Blyth, Eleanor; Martinez de la Torre, Alberto

    2015-04-01

    It has long been understood that accurate prediction and warning of the impacts of severe weather requires an integrated approach to forecasting. This was well demonstrated in the UK throughout winter 2013/14 when an exceptional run of severe winter storms, often with damaging high winds and intense rainfall led to significant damage from the large waves and storm surge along coastlines, and from saturated soils, high river flows and significant flooding inland. The substantial impacts on individuals, businesses and infrastructure indicate a pressing need to understand better the value that might be delivered through more integrated environmental prediction. To address this need, the Met Office, Centre for Ecology & Hydrology and National Oceanography Centre have begun to develop the foundations of a coupled high resolution probabilistic forecast system for the UK at km-scale. This links together existing model components of the atmosphere, coastal ocean, land surface and hydrology. Our initial focus on a 2-year Prototype project will demonstrate the UK coupled prediction concept in research mode, including an analysis of the winter 2013/14 storms and its impacts. By linking science development to operational collaborations such as the UK Natural Hazards Partnership, we can ensure that science priorities are rooted in user requirements. This presentation will provide an overview of UK environmental prediction activities and an update on progress during the first year of the Prototype project. We will present initial results from the coupled model development and discuss the challenges to realise the potential of integrated regional coupled forecasting for improving predictions and applications.

  20. A new environmental chamber for evaluation of gas-phase chemical mechanisms and secondary aerosol formation

    NASA Astrophysics Data System (ADS)

    Carter, William P. L.; Cocker, David R.; Fitz, Dennis R.; Malkina, Irina L.; Bumiller, Kurt; Sauer, Claudia G.; Pisano, John T.; Bufalino, Charles; Song, Chen

    A new state-of-the-art indoor environmental chamber facility for the study of atmospheric processes leading to the formation of ozone and secondary organic aerosol (SOA) has been constructed and characterized. The chamber is designed for atmospheric chemical mechanism evaluation at low reactant concentrations under well-controlled environmental conditions. It consists of two collapsible 90 m 3 FEP Teflon film reactors on pressure-controlled moveable frameworks inside a temperature-controlled enclosure flushed with purified air. Solar radiation is simulated with either a 200 kW Argon arc lamp or multiple blacklamps. Results of initial characterization experiments, all carried out at ˜300-305 K under dry conditions, concerning NO x and formaldehyde offgasing, radical sources, particle loss rates, and background PM formation are described. Results of initial single organic-NO x and simplified ambient surrogate-NO x experiments to demonstrate the utility of the facility for mechanism evaluation under low NO x conditions are summarized and compared with the predictions of the SAPRC-99 chemical mechanism. Overall, the results of the initial characterization and evaluation indicate that this new environmental chamber can provide high quality mechanism evaluation data for experiments with NO x levels as low as ˜2 ppb, though the results indicate some problems with the gas-phase mechanism that need further study. Initial evaluation experiments for SOA formation, also carried out under dry conditions, indicate that the chamber can provide high quality secondary aerosol formation data at relatively low hydrocarbon concentrations.

  1. Global phase behavior of supercritical water - environmentally significant organic chemicals mixtures

    NASA Astrophysics Data System (ADS)

    Artemenko, S. V.; Mazur, V. A.

    Recent developments of the global phase equilibria studies of binary mixtures provide some basic ideas of how the required methods can be developed based on global phase diagrams for visualization of the phase behavior of mixtures. The mapping of the global equilibrium surface in the parameter space of the equation of state (EoS) model provides the most comprehensive system of criteria for predicting binary mixture phase behavior. The main types of phase behavior for environmentally significant organic chemicals in aqueous environments are considered using structure-property correlations for the critical parameters of substances. Analytic expressions for azeotropy prediction for cubic EoS are derived. A local mapping concept is introduced to describe thermodynamically consistently the saturation curve of water.

  2. Chemical approaches to the study of environmental diseases

    SciTech Connect

    Phillips, N.J.

    1986-01-01

    Cause-and-effect relationships are difficult to establish in chronic diseases which take years to develop. Awareness of the health hazards posed by long-term, low-level exposure to toxins has focused attention on causative environmental agents. Studies discussed here identified chemical factors potentially involved in the induction of chronic diseases. The novel spiroketal mycotoxins talaromycins A and B (C/sub 12/H/sub 22/O/sub 4/) were isolated from Talaromyces stipitatus, a fungus associated with fermenting silage. /sup 1/H NMR 2D COSY spectroscopy was used to distinguish isolated spin systems in the diastereomeric mixture and to facilitate the complete proton assignments of the pure isomers. Dipolar couplings between protons on different rings of the bicyclic system, observed by NOE difference and 2D Exchange spectroscopy, established the relative configuration of the ketal center. Extracts of the fungus Fusarium equiseti isolated from the home of genetically unrelated leukemia patients showed toxicity to mammals and immunosuppressive activity. Chronic byssinosis may result from accumulation of toxins in the lungs of long-term cotton mill workers.

  3. Shuttle sonic boom - Technology and predictions. [environmental impact

    NASA Technical Reports Server (NTRS)

    Holloway, P. F.; Wilhold, G. A.; Jones, J. H.; Garcia, F., Jr.; Hicks, R. M.

    1973-01-01

    Because the shuttle differs significantly in both geometric and operational characteristics from conventional supersonic aircraft, estimation of sonic boom characteristics required a new technology base. The prediction procedures thus developed are reviewed. Flight measurements obtained for both the ascent and entry phases of the Apollo 15 and 16 and for the ascent phase only of the Apollo 17 missions are presented which verify the techniques established for application to shuttle. Results of extensive analysis of the sonic boom overpressure characteristics completed to date are presented which indicate that this factor of the shuttle's environmental impact is predictable, localized, of short duration and acceptable. Efforts are continuing to define the shuttle sonic boom characteristics to a fine level of detail based on the final system design.

  4. Shuttle sonic boom - Technology and predictions. [environmental impact

    NASA Technical Reports Server (NTRS)

    Holloway, P. F.; Wilhold, G. A.; Jones, J. H.; Garcia, F., Jr.; Hicks, R. M.

    1973-01-01

    Because the shuttle differs significantly in both geometric and operational characteristics from conventional supersonic aircraft, estimation of sonic boom characteristics required a new technology base. The prediction procedures thus developed are reviewed. Flight measurements obtained for both the ascent and entry phases of the Apollo 15 and 16 and for the ascent phase only of the Apollo 17 missions are presented which verify the techniques established for application to shuttle. Results of extensive analysis of the sonic boom overpressure characteristics completed to date are presented which indicate that this factor of the shuttle's environmental impact is predictable, localized, of short duration and acceptable. Efforts are continuing to define the shuttle sonic boom characteristics to a fine level of detail based on the final system design.

  5. Prioritizing Environmental Chemicals for Obesity and Diabetes Outcomes Research: A Screening Approach Using ToxCast™ High-Throughput Data.

    PubMed

    Auerbach, Scott; Filer, Dayne; Reif, David; Walker, Vickie; Holloway, Alison C; Schlezinger, Jennifer; Srinivasan, Supriya; Svoboda, Daniel; Judson, Richard; Bucher, John R; Thayer, Kristina A

    2016-08-01

    Diabetes and obesity are major threats to public health in the United States and abroad. Understanding the role that chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals for testing beyond those already implicated in the literature is challenging. This review is intended to help researchers generate hypotheses about chemicals that may contribute to diabetes and to obesity-related health outcomes by summarizing relevant findings from the U.S. Environmental Protection Agency (EPA) ToxCast™ high-throughput screening (HTS) program. Our aim was to develop new hypotheses around environmental chemicals of potential interest for diabetes- or obesity-related outcomes using high-throughput screening data. We identified ToxCast™ assay targets relevant to several biological processes related to diabetes and obesity (insulin sensitivity in peripheral tissue, pancreatic islet and β cell function, adipocyte differentiation, and feeding behavior) and presented chemical screening data against those assay targets to identify chemicals of potential interest. The results of this screening-level analysis suggest that the spectrum of environmental chemicals to consider in research related to diabetes and obesity is much broader than indicated by research papers and reviews published in the peer-reviewed literature. Testing hypotheses based on ToxCast™ data will also help assess the predictive utility of this HTS platform. More research is required to put these screening-level analyses into context, but the information presented in this review should facilitate the development of new hypotheses. Auerbach S, Filer D, Reif D, Walker V, Holloway AC, Schlezinger J, Srinivasan S, Svoboda D, Judson R, Bucher JR, Thayer KA. 2016. Prioritizing environmental chemicals for obesity and diabetes outcomes research: a screening approach using ToxCast™ high-throughput data. Environ

  6. Prioritizing Environmental Chemicals for Obesity and Diabetes Outcomes Research: A Screening Approach Using ToxCast™ High-Throughput Data

    PubMed Central

    Auerbach, Scott; Filer, Dayne; Reif, David; Walker, Vickie; Holloway, Alison C.; Schlezinger, Jennifer; Srinivasan, Supriya; Svoboda, Daniel; Judson, Richard; Bucher, John R.; Thayer, Kristina A.

    2016-01-01

    Background: Diabetes and obesity are major threats to public health in the United States and abroad. Understanding the role that chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals for testing beyond those already implicated in the literature is challenging. This review is intended to help researchers generate hypotheses about chemicals that may contribute to diabetes and to obesity-related health outcomes by summarizing relevant findings from the U.S. Environmental Protection Agency (EPA) ToxCast™ high-throughput screening (HTS) program. Objectives: Our aim was to develop new hypotheses around environmental chemicals of potential interest for diabetes- or obesity-related outcomes using high-throughput screening data. Methods: We identified ToxCast™ assay targets relevant to several biological processes related to diabetes and obesity (insulin sensitivity in peripheral tissue, pancreatic islet and β cell function, adipocyte differentiation, and feeding behavior) and presented chemical screening data against those assay targets to identify chemicals of potential interest. Discussion: The results of this screening-level analysis suggest that the spectrum of environmental chemicals to consider in research related to diabetes and obesity is much broader than indicated by research papers and reviews published in the peer-reviewed literature. Testing hypotheses based on ToxCast™ data will also help assess the predictive utility of this HTS platform. Conclusions: More research is required to put these screening-level analyses into context, but the information presented in this review should facilitate the development of new hypotheses. Citation: Auerbach S, Filer D, Reif D, Walker V, Holloway AC, Schlezinger J, Srinivasan S, Svoboda D, Judson R, Bucher JR, Thayer KA. 2016. Prioritizing environmental chemicals for obesity and diabetes outcomes research

  7. Carcinogenicity prediction of noncongeneric chemicals by a support vector machine.

    PubMed

    Zhong, Min; Nie, Xianglei; Yan, Aixia; Yuan, Qipeng

    2013-05-20

    The ability to identify carcinogenic compounds is of fundamental importance to the safe application of chemicals. In this study, we generated an array of in silico models allowing the classification of compounds into carcinogenic and noncarcinogenic agents based on a data set of 852 noncongeneric chemicals collected from the Carcinogenic Potency Database (CPDBAS). Twenty-four molecular descriptors were selected by Pearson correlation, F-score, and stepwise regression analysis. These descriptors cover a range of physicochemical properties, including electrophilicity, geometry, molecular weight, size, and solubility. The descriptor mutagenic showed the highest correlation coefficient with carcinogenicity. On the basis of these descriptors, a support vector machine-based (SVM) classification model was developed and fine-tuned by a 10-fold cross-validation approach. Both the SVM model (Model A1) and the best model from the 10-fold cross-validation (Model B3) runs gave good results on the test set with prediction accuracy over 80%, sensitivity over 76%, and specificity over 82%. In addition, extended connectivity fingerprints (ECFPs) and the Toxtree software were used to analyze the functional groups and substructures linked to carcinogenicity. It was found that the results of both methods are in good agreement.

  8. Progress of environmental management and risk assessment of industrial chemicals in China.

    PubMed

    Wang, Hong; Yan, Zhen-Guang; Li, Hong; Yang, Ni-Yun; Leung, Kenneth M Y; Wang, Yi-Zhe; Yu, Ruo-Zhen; Zhang, Lai; Wang, Wan-Hua; Jiao, Cong-Ying; Liu, Zheng-Tao

    2012-06-01

    With China's rapid economic growth, chemical-related environmental issues have become increasingly prominent, and the environmental management of chemicals has garnered increased attention from the government. This review focuses on the current situation and the application of risk assessment in China's environmental management of industrial chemicals. The related challenges and research needs of the country are also discussed. The Chinese government promulgated regulations for the import and export of toxic chemicals in 1994. Regulations for new chemical substances came into force in 2003, and were revised in 2010 based on the concept of risk management. In order to support the implementation of new regulations, Guidance for Risk Assessment of Chemicals is under development in an attempt to provide the concepts and techniques of risk assessment. With increasing concern and financial support from Chinese government, China is embarking on the fast track of research and development in environmental management of industrial chemicals. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Revolution In Toxicity Testing And Risk Prediction For Chemicals In The Environment (ASA)

    EPA Science Inventory

    Addressing safety aspects of drugs and environmental chemicals relies extensively on animal testing; however, the quantity of chemicals needing assessment and challenges of species extrapolation require alternative approaches to traditional animal studies. Newer in vitro and in s...

  10. Predicting Toxic and Therapeutic Mechanisms of the ToxCast Chemical Library by Phenotypic Screening (SOT)

    EPA Science Inventory

    Addressing safety aspects of drugs and environmental chemicals relies extensively on animal testing. However the quantity of chemicals needing assessment and challenges of species extrapolation require development of alternative approaches. Using 8 primary human cell systems (Bio...

  11. Revolution In Toxicity Testing And Risk Prediction For Chemicals In The Environment (ASA)

    EPA Science Inventory

    Addressing safety aspects of drugs and environmental chemicals relies extensively on animal testing; however, the quantity of chemicals needing assessment and challenges of species extrapolation require alternative approaches to traditional animal studies. Newer in vitro and in s...

  12. Predicting Toxic and Therapeutic Mechanisms of the ToxCast Chemical Library by Phenotypic Screening (SOT)

    EPA Science Inventory

    Addressing safety aspects of drugs and environmental chemicals relies extensively on animal testing. However the quantity of chemicals needing assessment and challenges of species extrapolation require development of alternative approaches. Using 8 primary human cell systems (Bio...

  13. Using ToxCast in vitro Assays in the Hierarchical Quantitative Structure-Activity Relationship (QSAR) Modeling for Predicting in vivo Toxicity of Chemicals

    EPA Science Inventory

    The goal of chemical toxicology research is utilizing short term bioassays and/or robust computational methods to predict in vivo toxicity endpoints for chemicals. The ToxCast program established at the US Environmental Protection Agency (EPA) is addressing this goal by using ca....

  14. An Online Prediction Platform to Support the Environmental ...

    EPA Pesticide Factsheets

    Historical QSAR models are currently utilized across a broad range of applications within the U.S. Environmental Protection Agency (EPA). These models predict basic physicochemical properties (e.g., logP, aqueous solubility, vapor pressure), which are then incorporated into exposure, fate and transport models. Whereas the classical manner of publishing results in peer-reviewed journals remains appropriate, there are substantial benefits to be gained by providing enhanced, open access to the training data sets and resulting models. Benefits include improved transparency, more flexibility to expand training sets and improve model algorithms, and greater ability to independently characterize model performance both globally and in local areas of chemistry. We have developed a web-based prediction platform that uses open-source descriptors and modeling algorithms, employs modern cheminformatics technologies, and is tailored for ease of use by the toxicology and environmental regulatory community. This tool also provides web-services to meet both EPA’s projects and the modeling community at-large. The platform hosts models developed within EPA’s National Center for Computational Toxicology, as well as those developed by other EPA scientists and the outside scientific community. Recognizing that there are other on-line QSAR model platforms currently available which have additional capabilities, we connect to such services, where possible, to produce an integrated

  15. Integrating hydrology within a fully coupled environmental prediction system

    NASA Astrophysics Data System (ADS)

    Best, Martin; Lewis, Huw; Ashton, Heather; Blyth, Eleanor; Martinez, Alberto

    2017-04-01

    Historically the hydrological community and the community developing the land surface component of atmospheric models have both been tasked with representing the terrestrial hydrological cycle, but have focused on different ends, namely streamflow and evaporation respectively. To date the lack of computational resources and representative observations have limited the integration of the skills within these two communities. However, this is no longer the case. In addition, the drive toward fully integrated high resolution environmental prediction systems, coupling atmosphere, land and ocean on regional domains, requires an accurate representation for all aspects of terrestrial hydrology. Hence a new focus is emerging to integrate improved hydrological processes within the land surface components of atmospheric models. The UK Environmental Prediction (UKEP) project is a research experiment aimed at understanding the potential benefits for detailed environmental forecasting from a fully coupled atmosphere/land/ocean system at km-scale resolution for the UK. The prototype model utilises the Joint UK Land Environment Simulator (JULES) as its land surface component, coupled to the RFM river flow model. Although JULES has been previously used for climate studies that close the global water cycle, the JULES/RFM system has not been comprehensively evaluated for its ability to simulate river discharge. In this study we attempt some initial evaluation of the JULES/RFM system for all aspects of the terrestrial hydrological cycle, including evaporation, soil moisture and streamflow. In addition, comparisons are made between the results from the fully coupled environmental prediction system and stand alone JULES/RFM simulations forced by atmospheric driving data from the UK weather forecasting model. This provides an opportunity to assess the impact of fully coupled versus a one way coupled response for terrestrial hydrology. Finally we consider the potential for coupling JULES

  16. Chemometric Methods and Theoretical Molecular Descriptors in Predictive QSAR Modeling of the Environmental Behavior of Organic Pollutants

    NASA Astrophysics Data System (ADS)

    Gramatica, Paola

    This chapter surveys the QSAR modeling approaches (developed by the author's research group) for the validated prediction of environmental properties of organic pollutants. Various chemometric methods, based on different theoretical molecular descriptors, have been applied: explorative techniques (such as PCA for ranking, SOM for similarity analysis), modeling approaches by multiple-linear regression (MLR, in particular OLS), and classification methods (mainly k-NN, CART, CP-ANN). The focus of this review is on the main topics of environmental chemistry and ecotoxicology, related to the physico-chemical properties, the reactivity, and biological activity of chemicals of high environmental concern. Thus, the review deals with atmospheric degradation reactions of VOCs by tropospheric oxidants, persistence and long-range transport of POPs, sorption behavior of pesticides (Koc and leaching), bioconcentration, toxicity (acute aquatic toxicity, mutagenicity of PAHs, estrogen binding activity for endocrine disruptors compounds (EDCs)), and finally persistent bioaccumulative and toxic (PBT) behavior for the screening and prioritization of organic pollutants. Common to all the proposed models is the attention paid to model validation for predictive ability (not only internal, but also external for chemicals not participating in the model development) and checking of the chemical domain of applicability. Adherence to such a policy, requested also by the OECD principles, ensures the production of reliable predicted data, useful also in the new European regulation of chemicals, REACH.

  17. In Vitro Screening of Environmental Chemicals for Targeted Testing Prioritization: The ToxCast Project

    EPA Science Inventory

    Chemical toxicity testing is being transformed by advances in biology and computer modeling, concerns over animal use, and the thousands of environmental chemicals lacking toxicity data. The U.S. Environmental Protection Agency’s ToxCast program aims to address these concerns by ...

  18. In Vitro Screening of Environmental Chemicals for Targeted Testing Prioritization: The ToxCast Project

    EPA Science Inventory

    Chemical toxicity testing is being transformed by advances in biology and computer modeling, concerns over animal use, and the thousands of environmental chemicals lacking toxicity data. The U.S. Environmental Protection Agency’s ToxCast program aims to address these concerns by ...

  19. Environmental chemicals and breast cancer risk--a structural chemistry perspective.

    PubMed

    Weyandt, Jamie; Ellsworth, Rachel E; Hooke, Jeffrey A; Shriver, Craig D; Ellsworth, Darrell L

    2008-01-01

    In modern industrialized societies, people are exposed to thousands of naturally occurring and synthetic chemicals throughout their lifetime. Although certain occupational chemicals are known to be carcinogenic in humans, it has been difficult to definitively determine the adverse health effects of many environmental pollutants due to their tremendous chemical diversity and absence of a consistent structural motif. Many environmental chemicals are metabolized in the body to reactive intermediates that readily react with DNA to form modified bases known as adducts, while other compounds mimic the biological function of estrogen. Because environmental chemicals tend to accumulate in human tissues and have carcinogenic and/or estrogenic properties, there is heightened interest in determining whether environmental chemicals increase risk for endocrine-related cancers, including breast cancer. Breast cancer is the most common cancer in women worldwide, but established risk factors account for a relatively small proportion of cases and causative factors remain ambiguous and poorly defined. In this review, we outline the structural chemistry of environmental contaminants, describe mechanisms of carcinogenesis and molecular pathways through which these chemicals may exert detrimental health effects, review current knowledge of relationships between chemicals and breast cancer risk, and highlight future directions for research on environmental contributions to breast cancer. Improved understanding of the relationship between environmental chemicals and breast cancer will help to educate the general public about real and perceived dangers of these pollutants in our environment and has the potential to reduce individual risk by changing corporate practices and improving public health policies.

  20. Predicting effects of environmental change on a migratory herbivore

    USGS Publications Warehouse

    Stillman, R A; Wood, K A; Gilkerson, Whelan; Elkinton, E; Black, J. M.; Ward, David H.; Petrie, M.

    2015-01-01

    for which birds were disturbed. We discuss the consequences of these predictions for Black Brant conservation. A wide range of migratory species responses are expected in response to environmental change. Process-based models are potential tools to predict such responses and understand the mechanisms which underpin them.

  1. Development of structure-activity relationship rules for predicting carcinogenic potential of chemicals.

    PubMed

    Woo, Y T; Lai, D Y; Argus, M F; Arcos, J C

    1995-09-01

    Since the inception of Section 5 (Premanufacturing/Premarketing Notification, PMN) of the Toxic Substances Control Act (TSCA), structure-activity relationship (SAR) analysis has been effectively used by U.S. Environmental Protection Agency's (EPA) Structure Activity Team (SAT) in the assessment of potential carcinogenic hazard of new chemicals for which test data are not available. To capture, systematize and codify the Agency's predictive expertise in order to make it more widely available to assessors outside the TSCA program, a cooperative project was initiated to develop a knowledge rule-based expert system to mimic the thinking and reasoning of the SAT. In this communication, we describe the overall structure of this expert system, discuss the scientific bases and principles of SAR analysis of chemical carcinogens used in the development of SAR knowledge rules, and delineate the major factors/rules useful for assessing the carcinogenic potential of fibers, polymers, metals/metalloids and several major classes of organic chemicals. An integrative approach using available short-term predictive tests and non-cancer toxicological data to supplement SAR analysis has also been described.

  2. Fruit transpiration in kiwifruit: environmental drivers and predictive model

    PubMed Central

    Montanaro, Giuseppe; Dichio, Bartolomeo; Xiloyannis, Cristos; Lang, Alexander

    2012-01-01

    Background and aims In most fruit crops, storage quality varies greatly between regions and seasons, causing significant commercial loss. Understanding the sources of this variability will contribute to the knowledge of fruit developmental physiology and may also benefit commercial fruit production via altered managements that reduce it or forecasts that predict it. A causal-chain relationship is proposed to help elucidate the sources of variability in fruit storage quality: the weather →(i)→ fruit transpiration →(ii)→ fruit calcium →(iii)→ fruit storage quality. This paper explores the first link of this hypothesis, →(i)→, for Hayward kiwifruit using field measurements of fruit transpiration rate and concurrent meteorological recordings. The aims are to identify the key environmental variables driving fruit transpiration and develop a predictive fruit transpiration model. Methodology Fruit transpiration was determined hourly over several 24-h periods by recording weight loss of detached fruit, on Days 23, 35, 49, 65, 94 and 140 after full bloom. Meteorological records were made every 15 min throughout the season at an adjacent regional weather station. A model of fruit transpiration was developed in which the usual meteorological variables (radiation, temperature, windspeed and relative humidity) were incorporated in a Fick's Law transpiration flux equation. Principal results Fruit transpiration rate (i.e. the molar flux density, mmol cm−2 h−1) varied diurnally and decreased during the season. The dominant fruit variable governing transpiration rate was skin conductance and the dominant environmental variables were relative humidity and temperature. Radiation and windspeed were not significantly influential. Conclusions The model provides a good fit to the fruit transpiration rate measurements regardless of the time of day/night or the stage of fruit development. The model allows reasonably accurate and continuous predictions of fruit

  3. Fruit transpiration in kiwifruit: environmental drivers and predictive model.

    PubMed

    Montanaro, Giuseppe; Dichio, Bartolomeo; Xiloyannis, Cristos; Lang, Alexander

    2012-01-01

    In most fruit crops, storage quality varies greatly between regions and seasons, causing significant commercial loss. Understanding the sources of this variability will contribute to the knowledge of fruit developmental physiology and may also benefit commercial fruit production via altered managements that reduce it or forecasts that predict it. A causal-chain relationship is proposed to help elucidate the sources of variability in fruit storage quality: the weather →(i)→ fruit transpiration →(ii)→ fruit calcium →(iii)→ fruit storage quality. This paper explores the first link of this hypothesis, →(i)→, for Hayward kiwifruit using field measurements of fruit transpiration rate and concurrent meteorological recordings. The aims are to identify the key environmental variables driving fruit transpiration and develop a predictive fruit transpiration model. Fruit transpiration was determined hourly over several 24-h periods by recording weight loss of detached fruit, on Days 23, 35, 49, 65, 94 and 140 after full bloom. Meteorological records were made every 15 min throughout the season at an adjacent regional weather station. A model of fruit transpiration was developed in which the usual meteorological variables (radiation, temperature, windspeed and relative humidity) were incorporated in a Fick's Law transpiration flux equation. Fruit transpiration rate (i.e. the molar flux density, mmol cm(-2) h(-1)) varied diurnally and decreased during the season. The dominant fruit variable governing transpiration rate was skin conductance and the dominant environmental variables were relative humidity and temperature. Radiation and windspeed were not significantly influential. The model provides a good fit to the fruit transpiration rate measurements regardless of the time of day/night or the stage of fruit development. The model allows reasonably accurate and continuous predictions of fruit transpiration rate throughout fruit development based on standard

  4. Use of Geochemical Indices in Environmental Assessment of Soil; the Predictable and the Predictably Unpredictable

    NASA Astrophysics Data System (ADS)

    Mikkonen, Hannah; Clarke, Bradley; van de Graaff, Robert; Reichman, Suzie

    2016-04-01

    Geochemical correlations between common contaminants (Pb, Ni, As, Cr, Co and Zn) and earth metals, Fe and Mn, have been recommended as empirical tools to estimate "background" concentrations of metals in soil. A limited number of studies indicate that geochemical ratios between Pb, Ni, As, Cr, Co, V and Zn with scavenger metals Fe or Mn, are consistent between soils collected from different regions (Hamon et al. 2004, Myers and Thorbjornsen 2004). These studies have resulted in the incorporation of geochemical indices into Australian guidance, for derivation of ecological investigation levels for Ni, Cr, Cu and Zn. However, little research has been undertaken to assess the variation of geochemical patterns between soils derived from different parent materials or different weathering environments. A survey of background soils derived from four different parent materials, across Victoria, Australia, was undertaken, comprising collection of samples (n=640) from the surface (0 to 0.1 m) and sub-surface (0.3 to 0.6 m). Soil samples were collected from urban and rural areas of low disturbance, away from point sources of contamination. Samples were analysed for metals/metalloids and soil physical and chemical properties. Statistical review of results included regression and multivariate analysis. The results of the soil survey were compared against geochemical relationships reported within Australia and internationally. Compilation of results from this study and international data sets, indicates that geochemical relationships for metals Cr and V (in the format of log[Cr] = alog[Fe] +c) are predictable, not only between soils derived from different parent materials, but also between soils of different continents. Conversely, relationships between Zn and Fe, Pb and Fe, Cu and Fe, Co and Mn are variable, particularly within soils derived from alluvial sediments, which may have undergone periods of reducing conditions, resulting in dissociation from metal oxides. Broad

  5. A Comparison of Predictive Thermo and Water Solvation Property Prediction Tools and Experimental Data for Selected Traditional Chemical Warfare Agents and Simulants II: COSMO RS and COSMOTherm

    DTIC Science & Technology

    2017-04-01

    density Physical properties Chemical properties Theoretical prediction Chemical agents Simulants 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...SUMMARY The capability to accurately and reliably predict the physical and chemical properties of molecular compounds is highly desirable. In the...updated results. 1.2 Background The capability to predict the physical and chemical properties of chemical warfare agents is critical for the

  6. Identification and Prioritization of Chemical Mixtures from Environmental Residue Data

    EPA Science Inventory

    High throughput toxicity testing has greatly improved the speed at which single chemicals can be screened using in vitro methods. However, people are not exposed to a single chemical at a time, rather to a mixture of chemicals. Even with the increased speed of these methods, te...

  7. Identification and Prioritization of Chemical Mixtures from Environmental Residue Data

    EPA Science Inventory

    High throughput toxicity testing has greatly improved the speed at which single chemicals can be screened using in vitro methods. However, people are not exposed to a single chemical at a time, rather to a mixture of chemicals. Even with the increased speed of these methods, te...

  8. In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human induced pluripotent stem cell-derived model.

    PubMed

    Sirenko, Oksana; Grimm, Fabian A; Ryan, Kristen R; Iwata, Yasuhiro; Chiu, Weihsueh A; Parham, Frederick; Wignall, Jessica A; Anson, Blake; Cromwell, Evan F; Behl, Mamta; Rusyn, Ivan; Tice, Raymond R

    2017-03-01

    An important target area for addressing data gaps through in vitro screening is the detection of potential cardiotoxicants. Despite the fact that current conservative estimates relate at least 23% of all cardiovascular disease cases to environmental exposures, the identities of the causative agents remain largely uncharacterized. Here, we evaluate the feasibility of a combinatorial in vitro/in silico screening approach for functional and mechanistic cardiotoxicity profiling of environmental hazards using a library of 69 representative environmental chemicals and drugs. Human induced pluripotent stem cell-derived cardiomyocytes were exposed in concentration-response for 30min or 24h and effects on cardiomyocyte beating and cellular and mitochondrial toxicity were assessed by kinetic measurements of intracellular Ca(2+) flux and high-content imaging using the nuclear dye Hoechst 33342, the cell viability marker Calcein AM, and the mitochondrial depolarization probe JC-10. More than half of the tested chemicals exhibited effects on cardiomyocyte beating after 30min of exposure. In contrast, after 24h, effects on cell beating without concomitant cytotoxicity were observed in about one third of the compounds. Concentration-response data for in vitro bioactivity phenotypes visualized using the Toxicological Prioritization Index (ToxPi) showed chemical class-specific clustering of environmental chemicals, including pesticides, flame retardants, and polycyclic aromatic hydrocarbons. For environmental chemicals with human exposure predictions, the activity-to-exposure ratios between modeled blood concentrations and in vitro bioactivity were between one and five orders of magnitude. These findings not only demonstrate that some ubiquitous environmental pollutants might have the potential at high exposure levels to alter cardiomyocyte function, but also indicate similarities in the mechanism of these effects both within and among chemicals and classes.

  9. Advancing Environmental Prediction Capabilities for the Polar Regions and Beyond during The Year of Polar Prediction

    NASA Astrophysics Data System (ADS)

    Werner, Kirstin; Goessling, Helge; Hoke, Winfried; Kirchhoff, Katharina; Jung, Thomas

    2017-04-01

    Environmental changes in polar regions open up new opportunities for economic and societal operations such as vessel traffic related to scientific, fishery and tourism activities, and in the case of the Arctic also enhanced resource development. The availability of current and accurate weather and environmental information and forecasts will therefore play an increasingly important role in aiding risk reduction and safety management around the poles. The Year of Polar Prediction (YOPP) has been established by the World Meteorological Organization's World Weather Research Programme as the key activity of the ten-year Polar Prediction Project (PPP; see more on www.polarprediction.net). YOPP is an internationally coordinated initiative to significantly advance our environmental prediction capabilities for the polar regions and beyond, supporting improved weather and climate services. Scheduled to take place from mid-2017 to mid-2019, the YOPP core phase covers an extended period of intensive observing, modelling, prediction, verification, user-engagement and education activities in the Arctic and Antarctic, on a wide range of time scales from hours to seasons. The Year of Polar Prediction will entail periods of enhanced observational and modelling campaigns in both polar regions. With the purpose to close the gaps in the conventional polar observing systems in regions where the observation network is sparse, routine observations will be enhanced during Special Observing Periods for an extended period of time (several weeks) during YOPP. This will allow carrying out subsequent forecasting system experiments aimed at optimizing observing systems in the polar regions and providing insight into the impact of better polar observations on forecast skills in lower latitudes. With various activities and the involvement of a wide range of stakeholders, YOPP will contribute to the knowledge base needed to managing the opportunities and risks that come with polar climate change.

  10. Environmental Fate of Organophosphorus Compounds Related to Chemical Weapons

    SciTech Connect

    Davisson, M L; Love, A H; Vance, A; Reynolds, J G

    2005-02-08

    Man-made organophosphorus compounds have been widely distributed throughout our environment as pesticides since their development during and after WWII. Many important studies have documented their relative persistence and toxicity. Development and use of some organophosphorus compounds as nerve agents gave rise to a separate but parallel effort to understand environmental persistence. In this latter case, the experiments have focused mainly on evaporation rates and first-order reaction kinetics. However, because organophosphorus compounds are easily polarized, the ionic content of a surrounding media directly factors into these reaction rates, but limited work in this regard has been done under environmentally relevant conditions. Furthermore, limited experiments investigating persistence of these agents on soil has resulted in widely varying degradation rates. Not surprisingly, no studies have investigated affinities of organophosphorus nerve agents to mineral or organic matter typically found in soil. As a result, we initiated laboratory experiments on dilute concentrations of nerve agent O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX) to quantify persistence in simulated environmental aqueous conditions. A quantitative analytical method was developed for VX and its degradation products using High Performance Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (HPLC-ESI-MS). VX hydrolysis rate is known to have a pH-dependency, however, the type of buffer and the relative proportion of different nucleophiles in solution significantly affect the overall rate and mechanism of degradation. For example, dissolved carbonate, a weak nucleophile dominating natural water, yielded pseudo-first order rate constants of {approx} 8 x 10{sup -3}/hr at pH 5 and 2 x 10{sup -2}/hr at pH 11. This small pH-dependent variation departs significantly from widely accepted rates at this pH range (4 x 10{sup -4}/hr to 8 x 10{sup -2}/hr) that were based on

  11. Toward seamless weather-climate and environmental prediction

    NASA Astrophysics Data System (ADS)

    Brunet, Gilbert

    2016-04-01

    Over the last decade or so, predicting the weather, climate and atmospheric composition has emerged as one of the most important areas of scientific endeavor. This is partly because the remarkable increase in skill of current weather forecasts has made society more and more dependent on them day to day for a whole range of decision making. And it is partly because climate change is now widely accepted and the realization is growing rapidly that it will affect every person in the world profoundly, either directly or indirectly. One of the important endeavors of our societies is to remain at the cutting-edge of modelling and predicting the evolution of the fully coupled environmental system: atmosphere (weather and composition), oceans, land surface (physical and biological), and cryosphere. This effort will provide an increasingly accurate and reliable service across all the socio-economic sectors that are vulnerable to the effects of adverse weather and climatic conditions, whether now or in the future. This emerging challenge was at the center of the World Weather Open Science Conference (Montreal, 2014).The outcomes of the conference are described in the World Meteorological Organization (WMO) book: Seamless Prediction of the Earth System: from Minutes to Months, (G. Brunet, S. Jones, P. Ruti Eds., WMO-No. 1156, 2015). It is freely available on line at the WMO website. We will discuss some of the outcomes of the conference for the WMO World Weather Research Programme (WWRP) and Global Atmospheric Watch (GAW) long term goals and provide examples of seamless modelling and prediction across a range of timescales at convective and sub-kilometer scales for regional coupled forecasting applications at Environment and Climate Change Canada (ECCC).

  12. Fast and accurate predictions of covalent bonds in chemical space.

    PubMed

    Chang, K Y Samuel; Fias, Stijn; Ramakrishnan, Raghunathan; von Lilienfeld, O Anatole

    2016-05-07

    We assess the predictive accuracy of perturbation theory based estimates of changes in covalent bonding due to linear alchemical interpolations among molecules. We have investigated σ bonding to hydrogen, as well as σ and π bonding between main-group elements, occurring in small sets of iso-valence-electronic molecules with elements drawn from second to fourth rows in the p-block of the periodic table. Numerical evidence suggests that first order Taylor expansions of covalent bonding potentials can achieve high accuracy if (i) the alchemical interpolation is vertical (fixed geometry), (ii) it involves elements from the third and fourth rows of the periodic table, and (iii) an optimal reference geometry is used. This leads to near linear changes in the bonding potential, resulting in analytical predictions with chemical accuracy (∼1 kcal/mol). Second order estimates deteriorate the prediction. If initial and final molecules differ not only in composition but also in geometry, all estimates become substantially worse, with second order being slightly more accurate than first order. The independent particle approximation based second order perturbation theory performs poorly when compared to the coupled perturbed or finite difference approach. Taylor series expansions up to fourth order of the potential energy curve of highly symmetric systems indicate a finite radius of convergence, as illustrated for the alchemical stretching of H2 (+). Results are presented for (i) covalent bonds to hydrogen in 12 molecules with 8 valence electrons (CH4, NH3, H2O, HF, SiH4, PH3, H2S, HCl, GeH4, AsH3, H2Se, HBr); (ii) main-group single bonds in 9 molecules with 14 valence electrons (CH3F, CH3Cl, CH3Br, SiH3F, SiH3Cl, SiH3Br, GeH3F, GeH3Cl, GeH3Br); (iii) main-group double bonds in 9 molecules with 12 valence electrons (CH2O, CH2S, CH2Se, SiH2O, SiH2S, SiH2Se, GeH2O, GeH2S, GeH2Se); (iv) main-group triple bonds in 9 molecules with 10 valence electrons (HCN, HCP, HCAs, HSiN, HSi

  13. Fast and accurate predictions of covalent bonds in chemical space

    NASA Astrophysics Data System (ADS)

    Chang, K. Y. Samuel; Fias, Stijn; Ramakrishnan, Raghunathan; von Lilienfeld, O. Anatole

    2016-05-01

    We assess the predictive accuracy of perturbation theory based estimates of changes in covalent bonding due to linear alchemical interpolations among molecules. We have investigated σ bonding to hydrogen, as well as σ and π bonding between main-group elements, occurring in small sets of iso-valence-electronic molecules with elements drawn from second to fourth rows in the p-block of the periodic table. Numerical evidence suggests that first order Taylor expansions of covalent bonding potentials can achieve high accuracy if (i) the alchemical interpolation is vertical (fixed geometry), (ii) it involves elements from the third and fourth rows of the periodic table, and (iii) an optimal reference geometry is used. This leads to near linear changes in the bonding potential, resulting in analytical predictions with chemical accuracy (˜1 kcal/mol). Second order estimates deteriorate the prediction. If initial and final molecules differ not only in composition but also in geometry, all estimates become substantially worse, with second order being slightly more accurate than first order. The independent particle approximation based second order perturbation theory performs poorly when compared to the coupled perturbed or finite difference approach. Taylor series expansions up to fourth order of the potential energy curve of highly symmetric systems indicate a finite radius of convergence, as illustrated for the alchemical stretching of H 2+ . Results are presented for (i) covalent bonds to hydrogen in 12 molecules with 8 valence electrons (CH4, NH3, H2O, HF, SiH4, PH3, H2S, HCl, GeH4, AsH3, H2Se, HBr); (ii) main-group single bonds in 9 molecules with 14 valence electrons (CH3F, CH3Cl, CH3Br, SiH3F, SiH3Cl, SiH3Br, GeH3F, GeH3Cl, GeH3Br); (iii) main-group double bonds in 9 molecules with 12 valence electrons (CH2O, CH2S, CH2Se, SiH2O, SiH2S, SiH2Se, GeH2O, GeH2S, GeH2Se); (iv) main-group triple bonds in 9 molecules with 10 valence electrons (HCN, HCP, HCAs, HSiN, HSi

  14. Predicting the evolution of fast chemical reactions in chaotic flows.

    PubMed

    Tsang, Yue-Kin

    2009-08-01

    We study the fast irreversible bimolecular reaction in a two-dimensional chaotic flow. The reactants are initially segregated and together fill the whole domain. Simulations show that the reactant concentration decays exponentially with rate lambda and then crosses over to the algebraic law of chemical kinetics in the final stage of the reaction. We estimate the crossover time from the reaction rate constant and the flow parameters. The exponential decay phase of the reaction can be described in terms of an equivalent passive scalar problem, allowing us to predict lambda using the theory of passive scalar advection. Depending on the relative length scale between the velocity and the concentration fields, lambda is either related to the distribution of the finite-time Lyapunov exponent of the flow or given in terms of an effective diffusivity which is independent of the small-scale stretching properties of the flow. For the former case, we suggest an optimal choice of flow parameters at which lambda is maximum.

  15. 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...

  16. About Using Predictive Models and Tools To Assess Chemicals under TSCA

    EPA Pesticide Factsheets

    As part of EPA's effort to promote chemical safety, OPPT provides public access to predictive models and tools which can help inform the public on the hazards and risks of substances and improve chemical management decisions.

  17. 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...

  18. PREDICTING TOXICOLOGICAL ENDPOINTS OF CHEMICALS USING QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSARS)

    EPA Science Inventory

    Quantitative structure-activity relationships (QSARs) are being developed to predict the toxicological endpoints for untested chemicals similar in structure to chemicals that have known experimental toxicological data. Based on a very large number of predetermined descriptors, a...

  19. AI AND SAR APPROACHES FOR PREDICTING CHEMICAL CARCINOGENICITY: SURVEY AND STATUS REPORT

    EPA Science Inventory

    A wide variety of artificial intelligence (AI) and structure-activity relationship (SAR approaches have been applied to tackling the general problem of predicting rodent chemical carcinogenicity. Given the diversity of chemical structures and mechanisms relative to this endpoin...

  20. AI AND SAR APPROACHES FOR PREDICTING CHEMICAL CARCINOGENICITY: SURVEY AND STATUS REPORT

    EPA Science Inventory

    A wide variety of artificial intelligence (AI) and structure-activity relationship (SAR approaches have been applied to tackling the general problem of predicting rodent chemical carcinogenicity. Given the diversity of chemical structures and mechanisms relative to this endpoin...

  1. PREDICTING TOXICOLOGICAL ENDPOINTS OF CHEMICALS USING QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSARS)

    EPA Science Inventory

    Quantitative structure-activity relationships (QSARs) are being developed to predict the toxicological endpoints for untested chemicals similar in structure to chemicals that have known experimental toxicological data. Based on a very large number of predetermined descriptors, a...

  2. 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.

  3. In silico prediction of toxicity of non-congeneric industrial chemicals using ensemble learning based modeling approaches

    SciTech Connect

    Singh, Kunwar P. Gupta, Shikha

    2014-03-15

    Ensemble learning approach based decision treeboost (DTB) and decision tree forest (DTF) models are introduced in order to establish quantitative structure–toxicity relationship (QSTR) for the prediction of toxicity of 1450 diverse chemicals. Eight non-quantum mechanical molecular descriptors were derived. Structural diversity of the chemicals was evaluated using Tanimoto similarity index. Stochastic gradient boosting and bagging algorithms supplemented DTB and DTF models were constructed for classification and function optimization problems using the toxicity end-point in T. pyriformis. Special attention was drawn to prediction ability and robustness of the models, investigated both in external and 10-fold cross validation processes. In complete data, optimal DTB and DTF models rendered accuracies of 98.90%, 98.83% in two-category and 98.14%, 98.14% in four-category toxicity classifications. Both the models further yielded classification accuracies of 100% in external toxicity data of T. pyriformis. The constructed regression models (DTB and DTF) using five descriptors yielded correlation coefficients (R{sup 2}) of 0.945, 0.944 between the measured and predicted toxicities with mean squared errors (MSEs) of 0.059, and 0.064 in complete T. pyriformis data. The T. pyriformis regression models (DTB and DTF) applied to the external toxicity data sets yielded R{sup 2} and MSE values of 0.637, 0.655; 0.534, 0.507 (marine bacteria) and 0.741, 0.691; 0.155, 0.173 (algae). The results suggest for wide applicability of the inter-species models in predicting toxicity of new chemicals for regulatory purposes. These approaches provide useful strategy and robust tools in the screening of ecotoxicological risk or environmental hazard potential of chemicals. - Graphical abstract: Importance of input variables in DTB and DTF classification models for (a) two-category, and (b) four-category toxicity intervals in T. pyriformis data. Generalization and predictive abilities of the

  4. Prediction and Prevention of Chemical Reaction Hazards: Learning by Simulation.

    ERIC Educational Resources Information Center

    Shacham, Mordechai; Brauner, Neima; Cutlip, Michael B.

    2001-01-01

    Points out that chemical hazards are the major cause of accidents in chemical industry and describes a safety teaching approach using a simulation. Explains a problem statement on exothermic liquid-phase reactions. (YDS)

  5. Prediction and Prevention of Chemical Reaction Hazards: Learning by Simulation.

    ERIC Educational Resources Information Center

    Shacham, Mordechai; Brauner, Neima; Cutlip, Michael B.

    2001-01-01

    Points out that chemical hazards are the major cause of accidents in chemical industry and describes a safety teaching approach using a simulation. Explains a problem statement on exothermic liquid-phase reactions. (YDS)

  6. Why small and medium chemical companies continue to pose severe environmental risks in rural China.

    PubMed

    He, Guizhen; Zhang, Lei; Mol, Arthur P J; Wang, Tieyu; Lu, Yonglong

    2014-02-01

    In China, rural chemical SMEs are often believed to still largely operate below the sustainability radar. This paper investigates to what extent and how chemical SMEs are already experiencing pressure to improve their environmental performance, using an in-depth case study in Jasmine County, Hebei province. The results show that local residents had rather low trust in the environmental improvement promises made by the enterprises and the local government, and disagreed with the proposed improvement plans. Although the power of local residents to influence decision making remained limited, the chemical SMEs started to feel increasing pressures to clean up their business, from governments, local communities and civil society, and international value chain stakeholders. Notwithstanding these mounting pressures chemical SME's environmental behavior and performance has not changed radically for the better. The strong economic ties between local county governments and chemical SMEs continue to be a major barrier for stringent environmental regulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Genetic and environmental factors affecting host response to drugs and other chemical compounds in our environment.

    PubMed Central

    Vesell, E S; Passananti, G T

    1977-01-01

    Compared to laboratory animals, humans are extremely heterogenous with respect to the many factors that can influence the distribution and biological effects of toxic chemicals. This heterogeneity can prevent an accurate assessment of the impact of a particular toxic compound on the health of an individual subject. Some of the factors that can significantly modify the host response to certain drugs, which serve in this review as a model for environmental chemicals, are enumerated and discussed. Although the mechanisms by which many of these factors modify the biological effects of certain environmental chemicals and drugs have been determined in some cases, better definition of the nature of interactions between these factors and environmental chemicals in a particular individual is required at a biochemical and molecular level. Recommendations are offered for the further development of our knowledge concerning interactions between environmental chemicals and such factors in a particular individual. PMID:598349

  8. Model to predict aerial dispersal of bacteria during environmental release.

    PubMed Central

    Knudsen, G R

    1989-01-01

    Risk assessment for genetically engineered bacteria sprayed onto crops includes determination of off-site dispersal and deposition. The ability to predict microbial dispersal patterns is essential to characterize the uncertainty (risk) associated with environmental release of recombinant organisms. Toward this end, a particle dispersal model was developed to predict recovery of bacteria on fallout plates at various distances and directions about a test site. The microcomputer simulation incorporates particle size distribution, wind speed and direction, turbulence, evaporation, sedimentation, and mortality, with a time step of 0.5 s. The model was tested against data reported from three field applications of nonrecombinant bacteria and two applications of recombinant bacteria. Simulated dispersal of 10(5) particles was compared with reported deposition measurements. The model may be useful in defining appropriate populations of organisms for release, methods of release or application, characteristics of a release site that influence containment or dispersal, and in developing an appropriate sampling methodology for monitoring the dispersal of organisms such as genetically engineered bacteria. PMID:2604402

  9. High Throughput Heuristics for Prioritizing Human Exposure to Environmental Chemicals

    EPA Science Inventory

    The risk posed to human health by any of the thousands of untested anthropogenic chemicals in our environment is a function of both the potential hazard presented by the chemical, and the possibility of being exposed. Without the capacity to make quantitative, albeit uncertain, f...

  10. High Throughput Heuristics for Prioritizing Human Exposure to Environmental Chemicals

    EPA Science Inventory

    The risk posed to human health by any of the thousands of untested anthropogenic chemicals in our environment is a function of both the potential hazard presented by the chemical, and the possibility of being exposed. Without the capacity to make quantitative, albeit uncertain, f...

  11. Agricultural Chemicals and Radiation. Ag Ed Environmental Education Series.

    ERIC Educational Resources Information Center

    Tulloch, Rodney W.

    The document is designed to be used as a resource in teaching vocational agriculture high school students about the environment. Agricultural chemicals are the major focus, with some attention to radiation. The importance of safety in agricultural chemical use is stressed, with descriptions of the pesticide label; protective clothing; respiratory…

  12. Monitoring, modelling and environmental exposure assessment of industrial chemicals in the aquatic environment.

    PubMed

    Holt, M S; Fox, K; Griessbach, E; Johnsen, S; Kinnunen, J; Lecloux, A; Murray-Smith, R; Peterson, D R; Schröder, R; Silvani, M; ten Berge, W F; Toy, R J; Feijtel, T C

    2000-12-01

    Monitoring and laboratory data play integral roles alongside fate and exposure models in comprehensive risk assessments. The principle in the European Union Technical Guidance Documents for risk assessment is that measured data may take precedence over model results but only after they are judged to be of adequate reliability and to be representative of the particular environmental compartments to which they are applied. In practice, laboratory and field data are used to provide parameters for the models, while monitoring data are used to validate the models' predictions. Thus, comprehensive risk assessments require the integration of laboratory and monitoring data with the model predictions. However, this interplay is often overlooked. Discrepancies between the results of models and monitoring should be investigated in terms of the representativeness of both. Certainly, in the context of the EU risk assessment of existing chemicals, the specific requirements for monitoring data have not been adequately addressed. The resources required for environmental monitoring, both in terms of manpower and equipment, can be very significant. The design of monitoring programmes to optimise the use of resources and the use of models as a cost-effective alternative are increasing in importance. Generic considerations and criteria for the design of new monitoring programmes to generate representative quality data for the aquatic compartment are outlined and the criteria for the use of existing data are discussed. In particular, there is a need to improve the accessibility to data sets, to standardise the data sets, to promote communication and harmonisation of programmes and to incorporate the flexibility to change monitoring protocols to amend the chemicals under investigation in line with changing needs and priorities.

  13. Do Interactions Between Gut Ecology and Environmental Chemicals Contribute to Obesity and Diabetes?

    PubMed Central

    Snedeker, Suzanne M.

    2011-01-01

    Background: Gut microbiota are important factors in obesity and diabetes, yet little is known about their role in the toxicodynamics of environmental chemicals, including those recently found to be obesogenic and diabetogenic. Objectives: We integrated evidence that independently links gut ecology and environmental chemicals to obesity and diabetes, providing a framework for suggesting how these environmental factors may interact with these diseases, and identified future research needs. Methods: We examined studies with germ-free or antibiotic-treated laboratory animals, and human studies that evaluated how dietary influences and microbial changes affected obesity and diabetes. Strengths and weaknesses of studies evaluating how environmental chemical exposures may affect obesity and diabetes were summarized, and research gaps on how gut ecology may affect the disposition of environmental chemicals were identified. Results: Mounting evidence indicates that gut microbiota composition affects obesity and diabetes, as does exposure to environmental chemicals. The toxicology and pharmacology literature also suggests that interindividual variations in gut microbiota may affect chemical metabolism via direct activation of chemicals, depletion of metabolites needed for biotransformation, alteration of host biotransformation enzyme activities, changes in enterohepatic circulation, altered bioavailability of environmental chemicals and/or antioxidants from food, and alterations in gut motility and barrier function. Conclusions: Variations in gut microbiota are likely to affect human toxicodynamics and increase individual exposure to obesogenic and diabetogenic chemicals. Combating the global obesity and diabetes epidemics requires a multifaceted approach that should include greater emphasis on understanding and controlling the impact of interindividual gut microbe variability on the disposition of environmental chemicals in humans. PMID:22042266

  14. Prioritizing chemicals for environmental management in China based on screening of potential risks

    NASA Astrophysics Data System (ADS)

    Yu, Xiangyi; Mao, Yan; Sun, Jinye; Shen, Yingwa

    2014-03-01

    The rapid development of China's chemical industry has created increasing pressure to improve the environmental management of chemicals. To bridge the large gap between the use and safe management of chemicals, we performed a comprehensive review of the international methods used to prioritize chemicals for environmental management. By comparing domestic and foreign methods, we confirmed the presence of this gap and identified potential solutions. Based on our literature review, we developed an appropriate screening method that accounts for the unique characteristics of chemical use within China. The proposed method is based on an evaluation using nine indices of the potential hazard posed by a chemical: three environmental hazard indices (persistence, bioaccumulation, and eco-toxicity), four health hazard indices (acute toxicity, carcinogenicity, mutagenicity, and reproductive and developmental toxicity), and two environmental exposure hazard indices (chemical amount and utilization pattern). The results of our screening agree with results of previous efforts from around the world, confirming the validity of the new system. The classification method will help decisionmakers to prioritize and identify the chemicals with the highest environmental risk, thereby providing a basis for improving chemical management in China.

  15. Overview of the ToxCast Research Program: Applications to Predictive Toxicology and Chemical Prioritization (SETAC)

    EPA Science Inventory

    Understanding the potential health risks posed by environmental chemicals is a significant challenge driven by the large number of diverse chemicals with generally uncharacterized exposures, mechanisms and toxicities. The U.S. EPA’s ToxCast chemical prioritization research projec...

  16. Overview of the ToxCast Research Program: Applications to Predictive Toxicology and Chemical Prioritization (SETAC)

    EPA Science Inventory

    Understanding the potential health risks posed by environmental chemicals is a significant challenge driven by the large number of diverse chemicals with generally uncharacterized exposures, mechanisms and toxicities. The U.S. EPA’s ToxCast chemical prioritization research projec...

  17. Integrated Environmental Risk Assessment and Whole-Process Management System in Chemical Industry Parks

    PubMed Central

    Shao, Chaofeng; Yang, Juan; Tian, Xiaogang; Ju, Meiting; Huang, Lei

    2013-01-01

    Chemical industry parks in China are considered high-risk areas because they present numerous risks that can damage the environment, such as pollution incidents. In order to identify the environmental risks and the principal risk factors in these areas, we have developed a simple physical model of a regional environmental risk field (ERF) using existing dispersal patterns and migration models. The regional ERF zoning was also conducted and a reference value for diagnostic methods was developed to determine risk-acceptable, risk-warning, and risk-mitigation zones, which can provide a risk source layout for chemical industry parks. In accordance with the environmental risk control requirements, this study focused on the three stages of control and management of environmental risk and established an environmental risk management system including risk source identification and assessment, environmental safety planning, early risk warning, emergency management, assessment of environmental effects, and environmental remediation of pollution accidents. By using this model, the environmental risks in Tianjin Binhai New Area, the largest chemical industry park in China, were assessed and the environmental risk zoning map was drawn, which suggested the existence of many unacceptable environmental risks in this area. Thus, relevant suggestions have been proposed from the perspective of the adjustment of risk source layout, intensified management of environmental risk control and so on. PMID:23603866

  18. Integrated environmental risk assessment and whole-process management system in chemical industry parks.

    PubMed

    Shao, Chaofeng; Yang, Juan; Tian, Xiaogang; Ju, Meiting; Huang, Lei

    2013-04-19

    Chemical industry parks in China are considered high-risk areas because they present numerous risks that can damage the environment, such as pollution incidents. In order to identify the environmental risks and the principal risk factors in these areas, we have developed a simple physical model of a regional environmental risk field (ERF) using existing dispersal patterns and migration models. The regional ERF zoning was also conducted and a reference value for diagnostic methods was developed to determine risk-acceptable, risk-warning, and risk-mitigation zones, which can provide a risk source layout for chemical industry parks. In accordance with the environmental risk control requirements, this study focused on the three stages of control and management of environmental risk and established an environmental risk management system including risk source identification and assessment, environmental safety planning, early risk warning, emergency management, assessment of environmental effects, and environmental remediation of pollution accidents. By using this model, the environmental risks in Tianjin Binhai New Area, the largest chemical industry park in China, were assessed and the environmental risk zoning map was drawn, which suggested the existence of many unacceptable environmental risks in this area. Thus, relevant suggestions have been proposed from the perspective of the adjustment of risk source layout, intensified management of environmental risk control and so on.

  19. 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...

  20. THE EFFECT OF ENVIRONMENTAL CHEMICALS ON HUMAN HEALTH -- USCF

    EPA Science Inventory

    Humans and animals have always been exposed to chemicals in our environment - natural products in foods, smoke from cooking fires, sewage in drinking water, pesticides from plants. However, the dramatic increases in industrialization over the past three centuries have dramatical...

  1. THE EFFECT OF ENVIRONMENTAL CHEMICALS ON HUMAN HEALTH

    EPA Science Inventory

    Humans and animals have always been exposed to chemicals in our environments - natural products in foods, smoke from cooking fires, sewage in drinking water, pesticides from plants. However, the dramatic increases in industrialization over the past three centuries have dramatica...

  2. The Effect of Environmental Chemicals on Human Health -- CJA

    EPA Science Inventory

    Humans and animals have always been exposed to chemicals in our environment - natural products in foods, smoke from cooking fires, sewage in drinking water, pesticides from plants. However, the dramatic increases in industrialization over the past three centuries have dramatical...

  3. The Effect of Environmental Chemicals on Human Health -- CJA

    EPA Science Inventory

    Humans and animals have always been exposed to chemicals in our environment - natural products in foods, smoke from cooking fires, sewage in drinking water, pesticides from plants. However, the dramatic increases in industrialization over the past three centuries have dramatical...

  4. THE EFFECT OF ENVIRONMENTAL CHEMICALS ON HUMAN HEALTH -- USCF

    EPA Science Inventory

    Humans and animals have always been exposed to chemicals in our environment - natural products in foods, smoke from cooking fires, sewage in drinking water, pesticides from plants. However, the dramatic increases in industrialization over the past three centuries have dramatical...

  5. THE EFFECT OF ENVIRONMENTAL CHEMICALS ON HUMAN HEALTH

    EPA Science Inventory

    Humans and animals have always been exposed to chemicals in our environments - natural products in foods, smoke from cooking fires, sewage in drinking water, pesticides from plants. However, the dramatic increases in industrialization over the past three centuries have dramatica...

  6. Environmental issues and work: women with multiple chemical sensitivities.

    PubMed

    Lipson, Juliene G; Doiron, Nathalie

    2006-08-01

    Multiple chemical sensitivities (MCS) is an acquired condition in which exposure to low levels of chemicals causes symptoms in multiple organ systems. Some 12%-16% of the U.S. population has some level of chemical sensitivity, 80% of whom are women. Attempts to reduce chemical exposures leads to enormous life difficulties at home, school, and workplace. We base our article on an ethnographic study of MCS in the United States and Canada. We describe here themes related to work issues in terms of a general trajectory of becoming sick from work exposures, coping with toxic physical environments and dealing with coworkers and, when unable to continue working, applying for workers' compensation, or disability status, or both.

  7. 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...

  8. ENVIRONMENTAL CHEMICAL MONITORING IN THE U.S.

    EPA Science Inventory

    Chemical monitoring of the environment is performed in the United States by Federal and State agencies, local governments, industries, organizations, and private individuals. The major reasons for monitoring are for compliance with laws and regulations, investigation of suspec...

  9. ENVIRONMENTAL CHEMICAL MONITORING IN THE U.S.

    EPA Science Inventory

    Chemical monitoring of the environment is performed in the United States by Federal and State agencies, local governments, industries, organizations, and private individuals. The major reasons for monitoring are for compliance with laws and regulations, investigation of suspec...

  10. Environmental chemicals and autoimmune disease: cause and effect.

    PubMed

    Hess, Evelyn V

    2002-12-27

    Many important clues have been provided by the relationship of certain medications to lupus and other autoimmune syndromes. These are temporary conditions that resolve when the medication is removed. There are now over 70 such medications which have been reported related to these autoimmune conditions. Interest continues to grow in the potential for environmental substances to cause these syndromes. Among those under suspicion are hydrazines, tartrazines, hair dyes, trichloroethylene, industrial emissions and hazardous wastes. Other possible associations include silica, mercury, cadmium, gold and L canavanine. Two recognised outbreaks include 'toxic oil syndrome' related to contaminated rape seed oil in Spain in 1981 and exposure to a contaminated environmental substance associated with an autoimmune attack on muscle tissue in 1989. Recently, there have been proposals made for the definition and identification of environmentally associated immune disorders. The World Health Organisation (WHO) has also provided recent publications for other environmentally related problems. All these aspects will be presented and reviewed in detail.

  11. Assays for endocrine-disrupting chemicals: Beyond environmental estrogens

    SciTech Connect

    Folmar, L.C.

    1999-07-01

    Recent popular and scientific articles have reported the presence of estrogenic and other hormone mimicking chemicals in the environment and their potential for causing reproductive dysfunction in humans and wildlife. The purpose of this session was to present the best available, if not standard, analytical methods to assay for the effects of xenobiotic chemicals on a broad range of endocrine-mediated events, including reproduction, growth, development and stress responses in aquatic vertebrate and invertebrate animals.

  12. New environmental concepts in the chemical and coke industries

    SciTech Connect

    A.Yu. Naletov; V.A. Naletov

    2007-05-15

    We know that environmentally pure technologies do not exist. Coke production is no exception to the rule. The article considers the logic of environmental decision making. Attention focuses on a new bank of ecologically appropriate materials whose release to the biosphere must be considered solely in quantititative terms. Qualitativily all these materials are familiar; they are assimilated by populations of microorganisms and tar thus compatible with the biosphere.

  13. Assessment of quantitative structure-activity relationship of toxicity prediction models for Korean chemical substance control legislation

    PubMed Central

    Kim, Kwang-Yon; Shin, Seong Eun; No, Kyoung Tai

    2015-01-01

    Objectives For successful adoption of legislation controlling registration and assessment of chemical substances, it is important to obtain sufficient toxicological experimental evidence and other related information. It is also essential to obtain a sufficient number of predicted risk and toxicity results. Particularly, methods used in predicting toxicities of chemical substances during acquisition of required data, ultimately become an economic method for future dealings with new substances. Although the need for such methods is gradually increasing, the-required information about reliability and applicability range has not been systematically provided. Methods There are various representative environmental and human toxicity models based on quantitative structure-activity relationships (QSAR). Here, we secured the 10 representative QSAR-based prediction models and its information that can make predictions about substances that are expected to be regulated. We used models that predict and confirm usability of the information expected to be collected and submitted according to the legislation. After collecting and evaluating each predictive model and relevant data, we prepared methods quantifying the scientific validity and reliability, which are essential conditions for using predictive models. Results We calculated predicted values for the models. Furthermore, we deduced and compared adequacies of the models using the Alternative non-testing method assessed for Registration, Evaluation, Authorization, and Restriction of Chemicals Substances scoring system, and deduced the applicability domains for each model. Additionally, we calculated and compared inclusion rates of substances expected to be regulated, to confirm the applicability. Conclusions We evaluated and compared the data, adequacy, and applicability of our selected QSAR-based toxicity prediction models, and included them in a database. Based on this data, we aimed to construct a system that can be used

  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. Prediction of glass durability as a function of environmental conditions

    SciTech Connect

    Jantzen, C M

    1988-01-01

    A thermodynamic model of glass durability is applied to natural, ancient, and nuclear waste glasses. The durabilities of over 150 different natural and man-made glasses, including actual ancient Roman and Islamic glasses (Jalame ca. 350 AD, Nishapur 10-11th century AD and Gorgon 9-11th century AD), are compared. Glass durability is a function of the thermodynamic hydration free energy, ..delta..G/sub hyd/, which can be calculated from glass composition and solution pH. The durability of the most durable nuclear waste glasses examined was /approximately/10/sup 6/ years. The least durable waste glass formulations were comparable in durability to the most durable simulated medieval window glasses of /approximately/10/sup 3/ years. In this manner, the durability of nuclear waste glasses has been interpolated to be /approximately/10/sup 6/ years and no less than 10/sup 3/ years. Hydration thermodynamics have been shown to be applicable to the dissolution of glass in various natural environments. Groundwater-glass interactions relative to geologic disposal of nuclear waste, hydration rind dating of obsidians, andor other archeological studies can be modeled, e.g., the relative durabilities of six simulated medieval window glasses have been correctly predicted for both laboratory (one month) and burial (5 years) experiments. Effects of solution pH on glass dissolution has been determined experimentally for the 150 different glasses and can be predicted theoretically by hydration thermodynamics. The effects of solution redox on dissolution of glass matrix elements such as SI and B have shown to be minimal. The combined effects of solution pH and Eh have been described and unified by construction of thermodynamically calculated Pourbaix (pH-Eh) diagrams for glass dissolution. The Pourbaix diagrams have been quantified to describe glass dissolution as a function of environmental conditions by use of the data derived from hydration thermodynamics. 56 refs., 7 figs.

  16. Factors Predicting the Ocular Surface Response to Desiccating Environmental Stress

    PubMed Central

    Alex, Anastasia; Edwards, Austin; Hays, J. Daniel; Kerkstra, Michelle; Shih, Amanda; de Paiva, Cintia S.; Pflugfelder, Stephen C.

    2013-01-01

    Purpose. To identify factors predicting the ocular surface response to experimental desiccating stress. Methods. The ocular surfaces of both eyes of 15 normal and 10 dry eye subjects wearing goggles were exposed to a controlled desiccating environment (15%–25% relative humidity and 2–5 L/min airflow) for 90 minutes. Eye irritation symptoms, blink rate, tear meniscus dimensions, noninvasive (RBUT) and invasive tear break-up time, and corneal fluorescein and conjunctival lissamine green-dye staining were recorded before and after desiccating stress. Pre- and postexposure measurements were compared, and Pearson correlations between clinical parameters before and after desiccating stress were calculated. Results. Corneal and conjunctival dye staining significantly increased in all subjects following 90-minute exposure to desiccating environment, and the magnitude of change was similar in normal and dry eye subjects; except superior cornea staining was greater in dry eye. Irritation severity in the desiccating environment was associated with baseline dye staining, baseline tear meniscus height, and blink rate after 45 minutes. Desiccation-induced change in corneal fluorescein staining was inversely correlated to baseline tear meniscus width, whereas change in total ocular surface dye staining was inversely correlated to baseline dye staining, RBUT, and tear meniscus height and width. Blink rate from 30 to 90 minutes in desiccating environment was higher in the dry eye than normal group. Blink rate significantly correlated to baseline corneal fluorescein staining and environmental-induced change in corneal fluorescein staining. Conclusions. Ocular surface dye staining increases in response to desiccating stress. Baseline ocular surface dye staining, tear meniscus height, and blink rate predict severity of ocular surface dye staining following exposure to a desiccating environment. PMID:23572103

  17. THYROID DISRUPTING CHEMICALS: CHALLENGES IN ASSESSING NEUROTOXIC RISK FROM ENVIRONMENTAL MIXTURES.

    EPA Science Inventory

    Environmental contaminants are known to act as thyroid disrupting chemicals (TDCs). Broadly defined, TDCs are xenobiotics that alter the structure or function of the thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeostasis, or change circulating o...

  18. IMPROVING THE ENVIRONMENTAL PERFORMANCE OF CHEMICAL PROCESSES THROUGH THE USE OF INFORMATION TECHNOLOGY

    EPA Science Inventory

    Efforts are currently underway at the USEPA to develop information technology applications to improve the environmental performance of the chemical process industry. These efforts include the use of genetic algorithms to optimize different process options for minimal environmenta...

  19. TRACI - THE TOOL FOR THE REDUCTION AND ASSESSMENT OF CHEMICAL AND OTHER ENVIRONMENTAL IMPACTS

    EPA Science Inventory

    TRACI, The Tool for the Reduction and Assessment of Chemical and other environmental Impacts, is described along with its history, the underlying research, methodologies, and insights within individual impact categories. TRACI facilitates the characterization of stressors that ma...

  20. THYROID DISRUPTING CHEMICALS: CHALLENGES IN ASSESSING NEUROTOXIC RISK FROM ENVIRONMENTAL MIXTURES.

    EPA Science Inventory

    Environmental contaminants are known to act as thyroid disrupting chemicals (TDCs). Broadly defined, TDCs are xenobiotics that alter the structure or function of the thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeostasis, or change circulating o...

  1. EPAs Actions to Restrict PFOA and Similar Chemicals Yield Significant Human Health and Environmental Benefits

    EPA Pesticide Factsheets

    WASHINGTON - To further agency and industry achievements, the U.S. Environmental Protection Agency (EPA) today proposed measures to ensure that perfluorinated chemicals that have been phased out do not re-enter the marketplace without review.

  2. Laser Applications to Chemical, Security, and Environmental Analysis: introduction to the feature issue

    SciTech Connect

    Dreizler, Andreas; Fried, Alan; Gord, James R

    2007-07-01

    This Applied Optics feature issue on Laser Applications to Chemical, Security,and Environmental Analysis (LACSEA) highlights papers presented at theLACSEA 2006 Tenth Topical Meeting sponsored by the Optical Society ofAmerica.

  3. Designing a Quantitative Structure-Activity Relationship for the Intrinsic Metabolic Clearance of Environmentally Relevant Chemicals

    EPA Science Inventory

    Toxicokinetic models serve a vital role in risk assessment by bridging the gap between chemical exposure and potentially toxic endpoints. While intrinsic metabolic clearance rates have a strong impact on toxicokinetics, limited data is available for environmentally relevant chemi...

  4. Designing a Quantitative Structure-Activity Relationship for the Intrinsic Metabolic Clearance of Environmentally Relevant Chemicals

    EPA Science Inventory

    Toxicokinetic models serve a vital role in risk assessment by bridging the gap between chemical exposure and potentially toxic endpoints. While intrinsic metabolic clearance rates have a strong impact on toxicokinetics, limited data is available for environmentally relevant chemi...

  5. Chemical Safety Alert: First Responders’ Environmental Liability Due To Mass Decontamination Runoff

    EPA Pesticide Factsheets

    CERCLA's good Samaritan provisions protect responders such as the Chemical Weapons Improved Response Team during lifesaving actions. Once imminent threats are addressed, responders should contain contamination and avoid/mitigate environmental consequences.

  6. IMPROVING THE ENVIRONMENTAL PERFORMANCE OF CHEMICAL PROCESSES THROUGH THE USE OF INFORMATION TECHNOLOGY

    EPA Science Inventory

    Efforts are currently underway at the USEPA to develop information technology applications to improve the environmental performance of the chemical process industry. These efforts include the use of genetic algorithms to optimize different process options for minimal environmenta...

  7. Comparison of cell type specificities of stress pathway reporter assay ensemble response to environmental chemicals.

    EPA Science Inventory

    The large number of environmental compounds that currently need characterization and prioritization for further toxicological study is a serious regulatory challenge facing the EPA. In addition to these agents comprising of pesticides, inerts, and high-production volume chemical...

  8. TRACI - THE TOOL FOR THE REDUCTION AND ASSESSMENT OF CHEMICAL AND OTHER ENVIRONMENTAL IMPACTS

    EPA Science Inventory

    TRACI, The Tool for the Reduction and Assessment of Chemical and other environmental Impacts, is described along with its history, the underlying research, methodologies, and insights within individual impact categories. TRACI facilitates the characterization of stressors that ma...

  9. Comparison of cell type specificities of stress pathway reporter assay ensemble response to environmental chemicals.

    EPA Science Inventory

    The large number of environmental compounds that currently need characterization and prioritization for further toxicological study is a serious regulatory challenge facing the EPA. In addition to these agents comprising of pesticides, inerts, and high-production volume chemical...

  10. 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...

  11. 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...

  12. Predicting Human Olfactory Perception from Chemical Features of Odor Molecules

    PubMed Central

    Keller, Andreas; Gerkin, Richard C.; Guan, Yuanfang; Dhurandhar, Amit; Turu, Gabor; Szalai, Bence; Mainland, Joel D.; Ihara, Yusuke; Yu, Chung Wen; Wolfinger, Russ; Vens, Celine; Schietgat, Leander; De Grave, Kurt; Norel, Raquel; Stolovitzky, Gustavo; Cecchi, Guillermo; Vosshall, Leslie B.; Meyer, Pablo

    2017-01-01

    It is still not possible to predict whether a given molecule will have a perceived odor, or what olfactory percept it will produce. We therefore organized the crowd-sourced DREAM Olfaction Prediction Challenge. Using a large olfactory psychophysical dataset, teams developed machine learning algorithms to predict sensory attributes of molecules based on their chemoinformatic features. The resulting models accurately predicted odor intensity and pleasantness, and also successfully predicted eight among 19 rated semantic descriptors (“garlic”, “fish”, “sweet”, “fruit,” “burnt”, “spices”, “flower”, “sour”). Regularized linear models performed nearly as well as random-forest-based ones, with a predictive accuracy that closely approaches a key theoretical limit. These models help to predict the perceptual qualities of virtually any molecule with high accuracy and also reverse-engineer the smell of a molecule. PMID:28219971

  13. Predicting human olfactory perception from chemical features of odor molecules.

    PubMed

    Keller, Andreas; Gerkin, Richard C; Guan, Yuanfang; Dhurandhar, Amit; Turu, Gabor; Szalai, Bence; Mainland, Joel D; Ihara, Yusuke; Yu, Chung Wen; Wolfinger, Russ; Vens, Celine; Schietgat, Leander; De Grave, Kurt; Norel, Raquel; Stolovitzky, Gustavo; Cecchi, Guillermo A; Vosshall, Leslie B; Meyer, Pablo

    2017-02-24

    It is still not possible to predict whether a given molecule will have a perceived odor or what olfactory percept it will produce. We therefore organized the crowd-sourced DREAM Olfaction Prediction Challenge. Using a large olfactory psychophysical data set, teams developed machine-learning algorithms to predict sensory attributes of molecules based on their chemoinformatic features. The resulting models accurately predicted odor intensity and pleasantness and also successfully predicted 8 among 19 rated semantic descriptors ("garlic," "fish," "sweet," "fruit," "burnt," "spices," "flower," and "sour"). Regularized linear models performed nearly as well as random forest-based ones, with a predictive accuracy that closely approaches a key theoretical limit. These models help to predict the perceptual qualities of virtually any molecule with high accuracy and also reverse-engineer the smell of a molecule. Copyright © 2017, American Association for the Advancement of Science.

  14. Predicting effects of environmental change on river inflows to ...

    EPA Pesticide Factsheets

    Estuarine river watersheds provide valued ecosystem services to their surrounding communities including drinking water, fish habitat, and regulation of estuarine water quality. However, the provisioning of these services can be affected by changes in the quantity and quality of river water, such as those caused by altered landscapes or shifting temperatures or precipitation. We used the ecohydrology model, VELMA, in the Trask River watershed to simulate the effects of environmental change scenarios on estuarine river inputs to Tillamook Bay (OR) estuary. The Trask River watershed is 453 km2 and contains extensive agriculture, silviculture, urban, and wetland areas. VELMA was parameterized using existing spatial datasets of elevation, soil type, land use, air temperature, precipitation, river flow, and water quality. Simulated land use change scenarios included alterations in the distribution of the nitrogen-fixing tree species Alnus rubra, and comparisons of varying timber harvest plans. Scenarios involving spatial and temporal shifts in air temperature and precipitation trends were also simulated. Our research demonstrates the utility of ecohydrology models such as VELMA to aid in watershed management decision-making. Model outputs of river water flow, temperature, and nutrient concentrations can be used to predict effects on drinking water quality, salmonid populations, and estuarine water quality. This modeling effort is part of a larger framework of

  15. Prediction of phylogeographic endemism in an environmentally complex biome

    PubMed Central

    Carnaval, Ana Carolina; Waltari, Eric; Rodrigues, Miguel T.; Rosauer, Dan; VanDerWal, Jeremy; Damasceno, Roberta; Prates, Ivan; Strangas, Maria; Spanos, Zoe; Rivera, Danielle; Pie, Marcio R.; Firkowski, Carina R.; Bornschein, Marcos R.; Ribeiro, Luiz F.; Moritz, Craig

    2014-01-01

    Phylogeographic endemism, the degree to which the history of recently evolved lineages is spatially restricted, reflects fundamental evolutionary processes such as cryptic divergence, adaptation and biological responses to environmental heterogeneity. Attempts to explain the extraordinary diversity of the tropics, which often includes deep phylogeographic structure, frequently invoke interactions of climate variability across space, time and topography. To evaluate historical versus contemporary drivers of phylogeographic endemism in a tropical system, we analyse the effects of current and past climatic variation on the genetic diversity of 25 vertebrates in the Brazilian Atlantic rainforest. We identify two divergent bioclimatic domains within the forest and high turnover around the Rio Doce. Independent modelling of these domains demonstrates that endemism patterns are subject to different climatic drivers. Past climate dynamics, specifically areas of relative stability, predict phylogeographic endemism in the north. Conversely, contemporary climatic heterogeneity better explains endemism in the south. These results accord with recent speleothem and fossil pollen studies, suggesting that climatic variability through the last 250 kyr impacted the northern and the southern forests differently. Incorporating sub-regional differences in climate dynamics will enhance our ability to understand those processes shaping high phylogeographic and species endemism, in the Neotropics and beyond. PMID:25122231

  16. Prediction of phylogeographic endemism in an environmentally complex biome.

    PubMed

    Carnaval, Ana Carolina; Waltari, Eric; Rodrigues, Miguel T; Rosauer, Dan; VanDerWal, Jeremy; Damasceno, Roberta; Prates, Ivan; Strangas, Maria; Spanos, Zoe; Rivera, Danielle; Pie, Marcio R; Firkowski, Carina R; Bornschein, Marcos R; Ribeiro, Luiz F; Moritz, Craig

    2014-10-07

    Phylogeographic endemism, the degree to which the history of recently evolved lineages is spatially restricted, reflects fundamental evolutionary processes such as cryptic divergence, adaptation and biological responses to environmental heterogeneity. Attempts to explain the extraordinary diversity of the tropics, which often includes deep phylogeographic structure, frequently invoke interactions of climate variability across space, time and topography. To evaluate historical versus contemporary drivers of phylogeographic endemism in a tropical system, we analyse the effects of current and past climatic variation on the genetic diversity of 25 vertebrates in the Brazilian Atlantic rainforest. We identify two divergent bioclimatic domains within the forest and high turnover around the Rio Doce. Independent modelling of these domains demonstrates that endemism patterns are subject to different climatic drivers. Past climate dynamics, specifically areas of relative stability, predict phylogeographic endemism in the north. Conversely, contemporary climatic heterogeneity better explains endemism in the south. These results accord with recent speleothem and fossil pollen studies, suggesting that climatic variability through the last 250 kyr impacted the northern and the southern forests differently. Incorporating sub-regional differences in climate dynamics will enhance our ability to understand those processes shaping high phylogeographic and species endemism, in the Neotropics and beyond. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  17. The Modification of Biocellular Chemical Reactions by Environmental Physicochemicals

    NASA Astrophysics Data System (ADS)

    Ishido, M.

    Environmental risk factors affect human biological system to different extent from modification of biochemical reaction to cellular catastrophe. There are considerable public concerns about electromagnetic fields and endocrine disruptors. Their risk assessments have not been fully achieved because of their scientific uncertainty: electromagnetic fields just modify the bioreaction in the restricted cells and endocrine disruptors are quite unique in that their expression is dependent on the exposure periods throughout a life. Thus, we here describe their molecular characterization to establish the new risk assessments for environmental physicochemicals.

  18. Leveraging Publically Available Chemical Functional Use Data in Support of Exposure Prediction

    EPA Science Inventory

    The U.S. EPA Exposure Forecasting (ExpoCast) project aims to provide rapid screening-level exposure predictions for thousands of chemicals, most of which lack detailed exposure data. Chemical functional use - the role a chemical plays in processes or products (e.g. solvent, ant...

  19. Leveraging Publically Available Chemical Functional Use Data in Support of Exposure Prediction

    EPA Science Inventory

    The U.S. EPA Exposure Forecasting (ExpoCast) project aims to provide rapid screening-level exposure predictions for thousands of chemicals, most of which lack detailed exposure data. Chemical functional use - the role a chemical plays in processes or products (e.g. solvent, ant...

  20. Predictive models for identifying the binding activity of structurally diverse chemicals to human pregnane X receptor.

    PubMed

    Yin, Cen; Yang, Xianhai; Wei, Mengbi; Liu, Huihui

    2017-07-12

    Toxic chemicals entered into human body would undergo a series of metabolism, transport and excretion, and the key roles played in there processes were metabolizing enzymes, which was regulated by the pregnane X receptor (PXR). However, some chemicals in environment could activate or antagonize human pregnane X receptor, thereby leading to a disturbance of normal physiological systems. In this study, based on a larger number of 2724 structurally diverse chemicals, we developed qualitative classification models by the k-nearest neighbor method. Moreover, the logarithm of 20 and 50% effective concentrations (log EC 20 and log EC 50) was used to establish quantitative structure-activity relationship (QSAR) models. With the classification model, two descriptors were enough to establish acceptable models, with the sensitivity, specificity, and accuracy being larger than 0.7, highlighting a high classification performance of the models. With two QSAR models, the statistics parameters with the correlation coefficient (R (2)) of 0.702-0.749 and the cross-validation and external validation coefficient (Q (2)) of 0.643-0.712, this indicated that the models complied with the criteria proposed in previous studies, i.e., R (2) > 0.6, Q (2) > 0.5. The small root mean square error (RMSE) of 0.254-0.414 and the good consistency between observed and predicted values proved satisfactory goodness of fit, robustness, and predictive ability of the developed QSAR models. Additionally, the applicability domains were characterized by the Euclidean distance-based approach and Williams plot, and results indicated that the current models had a wide applicability domain, which especially included a few classes of environmental contaminant, those that were not included in the previous models.

  1. Physico-chemical measurements of CL-20 for environmental applications. Comparison with RDX and HMX.

    PubMed

    Monteil-Rivera, Fanny; Paquet, Louise; Deschamps, Stéphane; Balakrishnan, Vimal K; Beaulieu, Chantale; Hawari, Jalal

    2004-01-30

    CL-20 is a polycyclic energetic nitramine, which may soon replace the monocyclic nitramines RDX and HMX, because of its superior explosive performance. Therefore, to predict its environmental fate, analytical and physico-chemical data must be made available. An HPLC technique was thus developed to measure CL-20 in soil samples based on the US Environmental Protection Agency method 8330. We found that the soil water content and aging (21 days) had no effect on the recoveries (>92%) of CL-20, provided that the extracts were kept acidic (pH 3). The aqueous solubility of CL-20 was poor (3.6 mg l(-1) at 25 degrees C) and increased with temperature to reach 18.5 mg l(-1) at 60 degrees C. The octanol-water partition coefficient of CL-20 (log KOW = 1.92) was higher than that of RDX (log KOW = 0.90) and HMX (log KOW = 0.16), indicating its higher affinity to organic matter. Finally, CL-20 was found to decompose in non-acidified water upon contact with glass containers to give NO2- (2 equiv.), N2O (2 equiv.), and HCOO- (2 equiv.). The experimental findings suggest that CL-20 should be less persistent in the environment than RDX and HMX.

  2. High Throughput Exposure Forecasts for Environmental Chemical Risk (SOT RASS)

    EPA Science Inventory

    Email Announcement to RASS: On December 11th we have rescheduled the webinar regarding progress and advances in exposure assessment, which was cancelled due to the government shutdown in October. Dr. Elaine Hubal, Deputy Director of the Chemical Safety for Sustainability (CSS) n...

  3. ASSAYS FOR ENDOCRINE DISRUPTING CHEMICALS: BEYOND ENVIRONMENTAL ESTROGENS

    EPA Science Inventory

    Recent popular and scientific articles have reported the presence of estrogenic and other hormone mimicking chemicals in the environment and their potential for causing reproductive dysfunction in humans and wildlife. The purpose of this session was to present the best available,...

  4. Environmental chemical mixtures: Assessing ecological exposure and effects in streams

    EPA Science Inventory

    This product is a USGS fact sheet that describes a collaborative effort between USGS and US EPA to characterize exposures to chemical mixtures and associated biological effects for a diverse range of US streams representing varying watershed size, land-use patterns, and ecotypes.

  5. High Throughput Exposure Forecasts for Environmental Chemical Risk (SOT RASS)

    EPA Science Inventory

    Email Announcement to RASS: On December 11th we have rescheduled the webinar regarding progress and advances in exposure assessment, which was cancelled due to the government shutdown in October. Dr. Elaine Hubal, Deputy Director of the Chemical Safety for Sustainability (CSS) n...

  6. High Throughput Pharmacokinetics for Environmental Chemicals (FutureToxII)

    EPA Science Inventory

    Pharmacokinetic (PK) models are critical to determine whether chemical exposures produce potentially hazardous tissue concentrations. For bioactivity identified in vitro (e.g. ToxCast) – hazardous or not – PK models can forecast exposure thresholds, below which no significant bio...

  7. Environmental chemical mixtures: Assessing ecological exposure and effects in streams

    EPA Science Inventory

    This product is a USGS fact sheet that describes a collaborative effort between USGS and US EPA to characterize exposures to chemical mixtures and associated biological effects for a diverse range of US streams representing varying watershed size, land-use patterns, and ecotypes.

  8. High Throughput Pharmacokinetics for Environmental Chemicals (FutureToxII)

    EPA Science Inventory

    Pharmacokinetic (PK) models are critical to determine whether chemical exposures produce potentially hazardous tissue concentrations. For bioactivity identified in vitro (e.g. ToxCast) – hazardous or not – PK models can forecast exposure thresholds, below which no significant bio...

  9. METHODS FOR INTEGRATING ENVIRONMENTAL CONSIDERATIONS INTO CHEMICAL PROCESS DESIGN DECISIONS

    EPA Science Inventory

    The objective of this cooperative agreement was to postulate a means by which an engineer could routinely include environmental considerations in day-to-day conceptual design problems; a means that could easily integrate with existing design processes, and thus avoid massive retr...

  10. DESIGNING EFFICIENT, ECONOMIC AND ENVIRONMENTALLY FRIENDLY CHEMICAL PROCESSES

    EPA Science Inventory

    A catalytic reforming process has been studied using hierarchical design and simulation calculations. Aproximations for the fugitive emissions indicate which streams allow the most value to be lost and which have the highest potential environmental impact. One can use tis inform...

  11. METHODS FOR INTEGRATING ENVIRONMENTAL CONSIDERATIONS INTO CHEMICAL PROCESS DESIGN DECISIONS

    EPA Science Inventory

    The objective of this cooperative agreement was to postulate a means by which an engineer could routinely include environmental considerations in day-to-day conceptual design problems; a means that could easily integrate with existing design processes, and thus avoid massive retr...

  12. DESIGNING EFFICIENT, ECONOMIC AND ENVIRONMENTALLY FRIENDLY CHEMICAL PROCESSES

    EPA Science Inventory

    A catalytic reforming process has been studied using hierarchical design and simulation calculations. Approximations for the fugitive emissions indicate which streams allow the most value to be lost and which have the highest potential environmental impact. One can use this infor...

  13. DESIGNING EFFICIENT, ECONOMIC AND ENVIRONMENTALLY FRIENDLY CHEMICAL PROCESSES

    EPA Science Inventory

    A catalytic reforming process has been studied using hierarchical design and simulation calculations. Approximations for the fugitive emissions indicate which streams allow the most value to be lost and which have the highest potential environmental impact. One can use this infor...

  14. THE ENVIRONMENTAL CHEMISTRY BRANCH - PROVIDING CHEMICAL ANSWERS TO ENVIRONMENTAL EXPOSURE AND RISK PROBLEMS

    EPA Science Inventory

    The Environmental Chemistry Branch (ECB) is part of the National Exposure Research Laboratory (NERL) within EPA's Office of Research and Development. ECB is located in NERL's Environmental Sciences Division in Las Vegas, Nevada. We are 15 Research Chemists and Environmental Scien...

  15. Progress in High Throughput Exposure Assessment for Prioritizing Human Exposure to Environmental Chemicals (SRA)

    EPA Science Inventory

    For thousands of chemicals in commerce, there is little or no information about exposure or health and ecological effects. The US Environmental Protection Agency (USEPA) has ongoing research programs to develop and evaluate models that use the often minimal chemical information a...

  16. Multiple Classes of Environmental Chemicals are Associated with Liver Disease: NHANES 2003-2006 [Journal Article

    EPA Science Inventory

    Biomonitoring of human tissues and fluids has shown that virtually all individuals, worldwide, carry a “body burden” of synthetic chemicals (Thornton et al. 2002; CDC 2009). Although the measurement of an environmental chemical in a person’s tissues or fluids is an indication of...

  17. Endocrine Profiling and Prioritization of Environmental Chemicals Using ToxCast Data

    EPA Science Inventory

    The prioritization of chemicals for toxicity testing is a primary goal of the U.S. EPA’s ToxCast™ program. Phase I of ToxCast utilized a battery of 467 in vitro, high-throughput screening assays to assess 309 environmental chemicals. One important mode of action leading to toxici...

  18. A Qualitative Comparison of Porcine and Rodent Thyroperoxidase -Effects of Environmental Chemicals.

    EPA Science Inventory

    A wide variety of environmental chemicals alter the function of the thyroid system in many animal species. Thyroperoxidase (TPO), the enzyme that synthesizes thyroid hormone, is one of the known biochemical targets for thyroid disrupting chemicals (TDC). The majority of the in vi...

  19. Identifying Candidate Chemical-Disease Linkages (Environmental and Epigenetic Determinants of IBD)

    EPA Science Inventory

    Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This h...

  20. WAR DSS: A DECISION SUPPORT SYSTEM FOR ENVIRONMENTALLY CONSCIOUS CHEMICAL PROCESS DESIGN

    EPA Science Inventory

    The second generation of the Waste Reduction (WAR) Algorithm is constructed as a decision support system (DSS) in the design of chemical manufacturing facilities. The WAR DSS is a software tool that can help reduce the potential environmental impacts (PEIs) of industrial chemical...

  1. 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.

  2. A Qualitative Comparison of Porcine and Rodent Thyroperoxidase -Effects of Environmental Chemicals.

    EPA Science Inventory

    A wide variety of environmental chemicals alter the function of the thyroid system in many animal species. Thyroperoxidase (TPO), the enzyme that synthesizes thyroid hormone, is one of the known biochemical targets for thyroid disrupting chemicals (TDC). The majority of the in vi...

  3. Multiple Classes of Environmental Chemicals are Associated with Liver Disease: NHANES 2003-2006 [Journal Article

    EPA Science Inventory

    Biomonitoring of human tissues and fluids has shown that virtually all individuals, worldwide, carry a “body burden” of synthetic chemicals (Thornton et al. 2002; CDC 2009). Although the measurement of an environmental chemical in a person’s tissues or fluids is an indication of...

  4. Endocrine Profiling and Prioritization of Environmental Chemicals Using ToxCast Data

    EPA Science Inventory

    The prioritization of chemicals for toxicity testing is a primary goal of the U.S. EPA’s ToxCast™ program. Phase I of ToxCast utilized a battery of 467 in vitro, high-throughput screening assays to assess 309 environmental chemicals. One important mode of action leading to toxici...

  5. Progress in High Throughput Exposure Assessment for Prioritizing Human Exposure to Environmental Chemicals (SRA)

    EPA Science Inventory

    For thousands of chemicals in commerce, there is little or no information about exposure or health and ecological effects. The US Environmental Protection Agency (USEPA) has ongoing research programs to develop and evaluate models that use the often minimal chemical information a...

  6. Chemical structure-based predictive model for the oxidation of trace organic contaminants by sulfate radical.

    PubMed

    Ye, Tiantian; Wei, Zongsu; Spinney, Richard; Tang, Chong-Jian; Luo, Shuang; Xiao, Ruiyang; Dionysiou, Dionysios D

    2017-06-01

    Second-order rate constants [Formula: see text] for the reaction of sulfate radical anion (SO4(•-)) with trace organic contaminants (TrOCs) are of scientific and practical importance for assessing their environmental fate and removal efficiency in water treatment systems. Here, we developed a chemical structure-based model for predicting [Formula: see text] using 32 molecular fragment descriptors, as this type of model provides a quick estimate at low computational cost. The model was constructed using the multiple linear regression (MLR) and artificial neural network (ANN) methods. The MLR method yielded adequate fit for the training set (Rtraining(2)=0.88,n=75) and reasonable predictability for the validation set (Rvalidation(2)=0.62,n=38). In contrast, the ANN method produced a more statistical robustness but rather poor predictability (Rtraining(2)=0.99andRvalidation(2)=0.42). The reaction mechanisms of SO4(•-) reactivity with TrOCs were elucidated. Our result shows that the coefficients of functional groups reflect their electron donating/withdrawing characters. For example, electron donating groups typically exhibit positive coefficients, indicating enhanced SO4(•-) reactivity. Electron withdrawing groups exhibit negative values, indicating reduced reactivity. With its quick and accurate features, we applied this structure-based model to 55 discrete TrOCs culled from the Contaminant Candidate List 4, and quantitatively compared their removal efficiency with SO4(•-) and OH in the presence of environmental matrices. This high-throughput model helps prioritize TrOCs that are persistent to SO4(•-) based oxidation technologies at the screening level, and provide diagnostics of SO4(•-) reaction mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Integrating Sustainable Development in Chemical Engineering Education: The Application of an Environmental Management System

    ERIC Educational Resources Information Center

    Montanes, M. T.; Palomares, A. E.; Sanchez-Tovar, R.

    2012-01-01

    The principles of sustainable development have been integrated in chemical engineering education by means of an environmental management system. These principles have been introduced in the teaching laboratories where students perform their practical classes. In this paper, the implementation of the environmental management system, the problems…

  8. Integrating Sustainable Development in Chemical Engineering Education: The Application of an Environmental Management System

    ERIC Educational Resources Information Center

    Montanes, M. T.; Palomares, A. E.; Sanchez-Tovar, R.

    2012-01-01

    The principles of sustainable development have been integrated in chemical engineering education by means of an environmental management system. These principles have been introduced in the teaching laboratories where students perform their practical classes. In this paper, the implementation of the environmental management system, the problems…

  9. Integrating Environmental Management in Chemical Engineering Education by Introducing an Environmental Management System in the Student's Laboratory

    ERIC Educational Resources Information Center

    Montanes, Maria T.; Palomares, Antonio E.

    2008-01-01

    In this work we show how specific challenges related to sustainable development can be integrated into chemical engineering education by introducing an environmental management system in the laboratory where the students perform their experimental lessons. It is shown how the system has been developed and implemented in the laboratory, what role…

  10. Integrating Environmental Management in Chemical Engineering Education by Introducing an Environmental Management System in the Student's Laboratory

    ERIC Educational Resources Information Center

    Montanes, Maria T.; Palomares, Antonio E.

    2008-01-01

    In this work we show how specific challenges related to sustainable development can be integrated into chemical engineering education by introducing an environmental management system in the laboratory where the students perform their experimental lessons. It is shown how the system has been developed and implemented in the laboratory, what role…

  11. Developing methods to assess and predict the population level effects of environmental contaminants.

    USGS Publications Warehouse

    Emlen, J.M.; Springman, K.R.

    2007-01-01

    The field of ecological toxicity seems largely to have drifted away from what its title implies--assessing and predicting the ecological consequences of environmental contaminants--moving instead toward an emphasis on individual effects and physiologic case studies. This paper elucidates how a relatively new ecological methodology, interaction assessment (INTASS), could be useful in addressing the field's initial goals. Specifically, INTASS is a model platform and methodology, applicable across a broad array of taxa and habitat types, that can be used to construct population dynamics models from field data. Information on environmental contaminants and multiple stressors can be incorporated into these models in a form that bypasses the problems inherent in assessing uptake, chemical interactions in the environment, and synergistic effects in the organism. INTASS can, therefore, be used to evaluate the effects of contaminants and other stressors at the population level and to predict how changes in stressor levels or composition of contaminant mixtures, as well as various mitigation measures, might affect population dynamics.

  12. Developing methods to assess and predict the population and community level effects of environmental contaminants

    USGS Publications Warehouse

    Emlen, John M.; Springman, Kathrine R.

    2007-01-01

    The field of ecological toxicity seems largely to have drifted away from what its title implies—assessing and predicting the ecological consequences of environmental contaminants—moving instead toward an emphasis on individual effects and physiologic case studies. This paper elucidates how a relatively new ecological methodology, interaction assessment (INTASS), could be useful in addressing the field's initial goals. Specifically, INTASS is a model platform and methodology, applicable across a broad array of taxa and habitat types, that can be used to construct population dynamics models from field data. Information on environmental contaminants and multiple stressors can be incorporated into these models in a form that bypasses the problems inherent in assessing uptake, chemical interactions in the environment, and synergistic effects in the organism. INTASS can, therefore, be used to evaluate the effects of contaminants and other stressors at the population level and to predict how changes in stressor levels or composition of contaminant mixtures, as well as various mitigation measures, might affect population dynamics.

  13. The contribution of household chemicals to environmental discharges via effluents: combining chemical and behavioural data.

    PubMed

    Richards, Samia; Paterson, Eric; Withers, Paul J A; Stutter, Marc

    2015-03-01

    Increased concentrations and loads of soluble, bioavailable forms of phosphorus (P) are a major cause of eutrophication in streams, rivers and lakes in many countries around the world. To implement P control measures, it is essential to identify P sources and their relative load contributions. A proportion of P loading generated from household wastewaters is derived from detergents yet the P compositions of the range of domestic detergents and their usage is poorly understood. To quantify P loads from household detergents, we analysed a large range of detergents and cleaning products commonly available in the UK and Europe, comparing regular and eco-labelled products. Chemical data were coupled with survey results on typical household detergents preferences and usage (n = 95 households). We also determined whether the major and trace element signatures of these household detergents could potentially be used as anthropogenic tracers in watercourses. The greatest P concentrations were found for regular dishwasher detergents (43-131 mg P/g detergent) whilst the range of P in eco-labelled dishwasher detergents was much lower (0.7-9.1 mg P/g detergent). Other household cleaning groups contained relatively smaller P concentrations. Considering the survey results, detergents' total P loading generated from one household using either regular or eco labelled products, was 0.414 and 0.021 kg P/year, respectively. Given a household occupancy of 2.7, the P load from all detergent use combined was 0.154 kg P/person/year of which the dishwasher contribution was 0.147 kg P/person/year. In terms of elemental signatures, (DWD) dishwasher detergents were significantly (P-value <0.001) different from other household cleaning products in their As, Na, TP, Si, Sr, SRP, Ti, Zn and Zr signatures. Na, P and B were all positively correlated with each other, indicating their potential use as a tracer suite for septic tank effluent in combination with other indices. We conclude that

  14. Variation in Environmentalism among University Students: Majoring in Outdoor Recreation, Parks, and Tourism Predicts Environmental Concerns and Behaviors

    ERIC Educational Resources Information Center

    Arnocky, Steven; Stroink, Mirella L.

    2011-01-01

    In a survey of Canadian university students (N = 205), the relationship between majoring in an outdoor recreation university program and environmental concern, cooperation, and behavior were examined. Stepwise linear regression indicated that enrollment in outdoor recreation was predictive of environmental behavior and ecological cooperation; and…

  15. Variation in Environmentalism among University Students: Majoring in Outdoor Recreation, Parks, and Tourism Predicts Environmental Concerns and Behaviors

    ERIC Educational Resources Information Center

    Arnocky, Steven; Stroink, Mirella L.

    2011-01-01

    In a survey of Canadian university students (N = 205), the relationship between majoring in an outdoor recreation university program and environmental concern, cooperation, and behavior were examined. Stepwise linear regression indicated that enrollment in outdoor recreation was predictive of environmental behavior and ecological cooperation; and…

  16. Novel flame retardants: Estimating the physical-chemical properties and environmental fate of 94 halogenated and organophosphate PBDE replacements.

    PubMed

    Zhang, Xianming; Sühring, Roxana; Serodio, Daniela; Bonnell, Mark; Sundin, Nils; Diamond, Miriam L

    2016-02-01

    In the wake of the listing by the Stockholm Convention of PBDEs, an increasing number of "novel" flame retardants (NFRs) are being used in products. The properties that make for desirable flame retardants can also lead to negative health effects, long environmental residence times and an affinity for organic matrices. While NFRs are currently in use, little information is available regarding their physical-chemical properties and environmental fate. In this study, 94 halogenated and organophosphate NFRs were evaluated for their persistence and long-range transport potential. Physical-chemical properties (namely liquid sub-cooled vapor pressure P(l) and solubility S(l), air-water (K(AW)), octanol-water (K(OW)), and octanol-air (K(OA)) partition coefficients) of the NFRs were predicted using three chemical property estimation tools: EPI Suite, SPARC and Absolv. Physical-chemical properties predicted using these tools were generally within 10(2)-10(3) for compounds with molecular weight < 800 g/mol. Estimated physical-chemical properties of compounds with >800 g/mol, and/or the presence of a heteroatom and/or a polar functional group could deviate by up to 10(12). According to the OECD P(OV) and LRTP Screening Tool, up to 40% of the NFRs have a persistence and/or long range transport potential of medium to high level of concern and up to 60% have persistence and or long range transport potential similar to the PBDEs they are replacing. Long range transport potential could be underestimated by the OECD model since the model under-predicts long range transport potential of some organophosphate compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. The decay of chemical weapons agents under environmental conditions

    SciTech Connect

    McGuire, R.R.; Haas, J.S.; Eagle, R.J.

    1993-04-09

    The rate and mechanism of decay of chemical agents in the environment was studied via live agent field trials at the chemical and Biological Defence Establishment, Porton Down, UK. The plan was to deposit the agents GD (Soman), VX, and H (sulfur mustard) on separate l-m{sup 2} plots on three successive days; i.e., Tuesday through Thursday. The depositions were to be made so as to give an areal concentration of 10 g/m{sup 2}. Four felt pads of approximately 25 cm{sup 2} each were placed at the corners of each of the test plots. These were subsequently extracted and analyzed by CBDE to determine the actual agent concentration. Samples for LLNL (two different types of soil, disks of silicone rubber gasket material, and short cylinders of concrete were to be contaminated and analyzed. Results are described.

  18. Molecular Ecology of Bacterial Population in Environmental Hazardous Chemical Control

    DTIC Science & Technology

    1993-01-14

    Pseudomonas putida F1 to measure toluene driven co-metabolic oxidation of TCE. (2) Demonstration of a new pathway for aerobic biodegradation of DDT...mediated by Alcaligenes eutrophus strain A5 previously shown competent for biodegradation of chlorobiphenyl congeners. (3) Confirmation that...the dynamics in microbial population density and activity during environmental biodegradation processes. Metabolism of PAHs. Pseudomonas £luorescens 5RL

  19. Optical chemical sensors for environmental control and system management

    NASA Astrophysics Data System (ADS)

    Tabacco, M. B.; Digiuseppe, T. G.

    Several fiber optic based chemical sensors have been developed for use in plant growth systems and enclosed life support systems. Optical chemical sensors offer several distinct advantages in terms of sensitivity, calibration stability, immunity to biofouling and electrical interference, and ease of multiplexing sensors for multipoint/multiparameter analysis. Also, the ability to locate fiber optic sensors in close proximity to plant roots or leaves should improve the measurement reliability by obviating the need for handling and transport which can compromise sample integrity. Polestar Technologies and GEO-CENTERS have developed and tested many types of optical chemical sensors which utilize novel glass and polymeric materials as the sensor substrate. Analytes are detected using immobilized colorimetric indication systems or molecular recognition elements. Typically transduction is via wavelength specific absorption changes with multiwavelength detection for drift compensation. Sensors have been developed for solution pH, NH_3, ethylene, CO_2, and dissolved metal ions. In addition, unique PC-compatible optoelectronic interfaces, as well as distributed measurement systems, so that integrated detection systems are now available. In this paper recent efforts to develop sensors for critical nutrient ions are presented.

  20. Molecular building blocks and their architecture in biologically/environmentally compatible soft matter chemical machinery.

    PubMed

    Toyota, Taro; Banno, Taisuke; Nitta, Sachiko; Takinoue, Masahiro; Nomoto, Tomonori; Natsume, Yuno; Matsumura, Shuichi; Fujinami, Masanori

    2014-01-01

    This review briefly summarizes recent developments in the construction of biologically/environmentally compatible chemical machinery composed of soft matter. Since environmental and living systems are open systems, chemical machinery must continuously fulfill its functions not only through the influx and generation of molecules but also via the degradation and dissipation of molecules. If the degradation or dissipation of soft matter molecular building blocks and biomaterial molecules/polymers can be achieved, soft matter particles composed of them can be used to realize chemical machinery such as selfpropelled droplets, drug delivery carriers, tissue regeneration scaffolds, protocell models, cell-/tissuemarkers, and molecular computing systems.

  1. Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression

    PubMed Central

    Nahta, Rita; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Andrade-Vieira, Rafaela; Bay, Sarah; G. Brown, Dustin; Calaf, Gloria M.; Castellino, Robert C.; Cohen-Solal, Karine A.; Colacci, Annamaria; Cruickshanks, Nichola; Dent, Paul; Di Fiore, Riccardo; Forte, Stefano; Goldberg, Gary S.; Hamid, Roslida A.; Krishnan, Harini; Laird, Dale W.; Lasfar, Ahmed; Marignani, Paola A.; Memeo, Lorenzo; Mondello, Chiara; Naus, Christian C.; Ponce-Cusi, Richard; Raju, Jayadev; Roy, Debasish; Roy, Rabindra; P. Ryan, Elizabeth; Salem, Hosni K.; Scovassi, A. Ivana; Singh, Neetu; Vaccari, Monica; Vento, Renza; Vondráček, Jan; Wade, Mark; Woodrick, Jordan; Bisson, William H.

    2015-01-01

    As part of the Halifax Project, this review brings attention to the potential effects of environmental chemicals on important molecular and cellular regulators of the cancer hallmark of evading growth suppression. Specifically, we review the mechanisms by which cancer cells escape the growth-inhibitory signals of p53, retinoblastoma protein, transforming growth factor-beta, gap junctions and contact inhibition. We discuss the effects of selected environmental chemicals on these mechanisms of growth inhibition and cross-reference the effects of these chemicals in other classical cancer hallmarks. PMID:26106139

  2. Endocrine-Disrupting Chemicals and Oil and Natural Gas Operations: Potential Environmental Contamination and Recommendations to Assess Complex Environmental Mixtures

    PubMed Central

    Kassotis, Christopher D.; Tillitt, Donald E.; Lin, Chung-Ho; McElroy, Jane A.; Nagel, Susan C.

    2015-01-01

    Background Hydraulic fracturing technologies, developed over the last 65 years, have only recently been combined with horizontal drilling to unlock oil and gas reserves previously deemed inaccessible. Although these technologies have dramatically increased domestic oil and natural gas production, they have also raised concerns for the potential contamination of local water supplies with the approximately 1,000 chemicals that are used throughout the process, including many known or suspected endocrine-disrupting chemicals. Objectives We discuss the need for an endocrine component to health assessments for drilling-dense regions in the context of hormonal and antihormonal activities for chemicals used. Methods We discuss the literature on a) surface and groundwater contamination by oil and gas extraction operations, and b) potential human exposure, particularly in the context of the total hormonal and antihormonal activities present in surface and groundwater from natural and anthropogenic sources; we also discuss initial analytical results and critical knowledge gaps. Discussion In light of the potential for environmental release of oil and gas chemicals that can disrupt hormone receptor systems, we recommend methods for assessing complex hormonally active environmental mixtures. Conclusions We describe a need for an endocrine-centric component for overall health assessments and provide information supporting the idea that using such a component will help explain reported adverse health trends as well as help develop recommendations for environmental impact assessments and monitoring programs. Citation Kassotis CD, Tillitt DE, Lin CH, McElroy JA, Nagel SC. 2016. Endocrine-disrupting chemicals and oil and natural gas operations: potential environmental contamination and recommendations to assess complex environmental mixtures. Environ Health Perspect 124:256–264; http://dx.doi.org/10.1289/ehp.1409535 PMID:26311476

  3. Predicting the environmental distribution of compounds with unknown physicochemical properties from known pesticide properties

    SciTech Connect

    Prasad, S.S.

    1991-01-01

    This study examines how pesticide characteristics such as water solubility, molecular weight, bioconcentration, volatility, and soil absorption affect soil-to-water mobility, water-to-air dissipation, and water-to-biota accumulation when present in the environmental medium of preferred residence. The study concludes that chemicals that have low water solubilities tend to adsorb to soil, those that have low vapor pressures tend to dissipate slowly from water, and those that have relatively high octanol-to-water partition coefficients or low water solubility have a high potential for bioconcentration. Based on these findings, researchers should be able to predict the mobility of pesticides belonging to a particular category or family of compounds with unknown physicochemical properties and recommend ways to restore the environment. 13 refs., 13 figs., 4 tabs.

  4. Improvements to enforcement of multilateral environmental agreements to control international shipments of chemicals and wastes.

    PubMed

    Liu, Ning; Somboon, Vira; Wun'gaeo, Surichai; Middleton, Carl; Tingsabadh, Charit; Limjirakan, Sangchan

    2016-06-01

    Illegal trade in hazardous waste and harmful chemicals has caused severe damage on human health and the environment, and brought big challenges to countries to meet their commitments to related multilateral environmental agreements. Synergy-building, like organising law enforcement operations, is critical to address illegal trade in waste and chemicals, and further improve the effectiveness of environmental enforcement. This article discusses how and why law enforcement operations can help countries to implement chemical and waste-related multilateral environmental agreements in a more efficient and effective way. The research explores key barriers and factors for organising law enforcement operations, and recommends methods to improve law enforcement operations to address illegal trade in hazardous waste and harmful chemicals.

  5. Mapping Proteome-Wide Targets of Environmental Chemicals using Reactivity-Based Chemoproteomic Platforms

    PubMed Central

    Medina-Cleghorn, Daniel; Bateman, Leslie A.; Ford, Breanna; Heslin, Ann; Fisher, Karl J.; Dalvie, Esha D.; Nomura, Daniel K.

    2015-01-01

    We are exposed to a growing number of chemicals in our environment, most of which have not been characterized in terms of their toxicological potential or mechanisms. Here, we employ a chemoproteomic platform to map the cysteine reactivity of environmental chemicals using reactivity-based probes to mine for hyper-reactive hotspots across the proteome. We show that environmental contaminants such as monomethylarsonous acid and widely used pesticides such as chlorothalonil and chloropicrin possess common reactivity with a distinct set of proteins. Many of these proteins are involved in key metabolic processes, suggesting that these targets may be particularly sensitive to environmental electrophiles. We show that the widely used fungicide chlorothalonil specifically inhibits several metabolic enzymes involved in fatty acid metabolism and energetics, leading to dysregulated lipid metabolism in mice. Our results underscore the utility of using reactivity-based chemoproteomic platforms to uncover novel mechanistic insights into the toxicity of environmental chemicals. PMID:26496688

  6. Environmental Chemical Analysis (by B. B. Kebbekus and S. Mitra)

    NASA Astrophysics Data System (ADS)

    Bower, Reviewed By Nathan W.

    1999-11-01

    This text helps to fill a void in the market, as there are relatively few undergraduate instrumental analysis texts designed specifically for the expanding population of environmental science students. R. N. Reeve's introductory, open-learning Environmental Analysis (Wiley, 1994) is one of the few, and it is aimed at a lower level and is less appropriate for traditional classroom study. Kebbekus and Mitra's book appears to be an update of I. Marr and M. Cresser's excellent 1983 text by the same name (and also published under the Chapman and Hall imprint). It assumes no background in instrumental methods of analysis but it does depend upon a good general chemistry background in kinetic and equilibrium calculations and the standard laboratory techniques found in a classical introduction to analytical chemistry. The slant taken by the authors is aimed more toward engineers, not only in the choice of topics, but also in how they are presented. For example, the statistical significance tests presented follow an engineering format rather than the standard used in analytical chemistry. This approach does not detract from the book's clarity. The writing style is concise and the book is generally well written. The earlier text, which has become somewhat of a classic, took the unusual step of teaching the instruments in the context of their environmental application. It was divided into sections on the "atmosphere", the "hydrosphere", the "lithosphere", and the "biosphere". This text takes a similar approach in the second half, with chapters on methods for air, water, and solid samples. Users who intend to use the book as a text instead of a reference will appreciate the addition of chapters in the first half of the book on spectroscopic, chromatographic, and mass spectrometric methods. The six chapters in these two parts of the book along with four chapters scattered throughout on environmental measurements, sampling, sample preparation, and quality assurance make a nice

  7. The dilemma in prioritizing chemicals for environmental analysis: known versus unknown hazards.

    PubMed

    Anna, Sobek; Sofia, Bejgarn; Christina, Rudén; Magnus, Breitholtz

    2016-08-10

    A major challenge for society is to manage the risks posed by the many chemicals continuously emitted to the environment. All chemicals in production and use cannot be monitored and science-based strategies for prioritization are essential. In this study we review available data to investigate which substances are included in environmental monitoring programs and published research studies reporting analyses of chemicals in Baltic Sea fish between 2000 and 2012. Our aim is to contribute to the discussion of priority settings in environmental chemical monitoring and research, which is closely linked to chemical management. In total, 105 different substances or substance groups were analyzed in Baltic Sea fish. Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) were the most studied substances or substance groups. The majority, 87%, of all analyses comprised 20% of the substances or substance groups, whereas 46 substance groups (44%) were analyzed only once. Almost three quarters of all analyses regarded a POP-substance (persistent organic pollutant). These results demonstrate that the majority of analyses on environmental contaminants in Baltic Sea fish concern a small number of already regulated chemicals. Legacy pollutants such as POPs pose a high risk to the Baltic Sea due to their hazardous properties. Yet, there may be a risk that prioritizations for chemical analyses are biased based on the knowns of the past. Such biases may lead to society failing in identifying risks posed by yet unknown hazardous chemicals. Alternative and complementary ways to identify priority chemicals are needed. More transparent communication between risk assessments performed as part of the risk assessment process within REACH and monitoring programs, and information on chemicals contained in consumer articles, would offer ways to identify chemicals for environmental analysis.

  8. Chemical Transformation Simulator

    EPA Science Inventory

    The Chemical Transformation Simulator (CTS) is a web-based, high-throughput screening tool that automates the calculation and collection of physicochemical properties for an organic chemical of interest and its predicted products resulting from transformations in environmental sy...

  9. Chemical Transformation Simulator

    EPA Science Inventory

    The Chemical Transformation Simulator (CTS) is a web-based, high-throughput screening tool that automates the calculation and collection of physicochemical properties for an organic chemical of interest and its predicted products resulting from transformations in environmental sy...

  10. Prediction of rodent carcinogenicity of further 30 chemicals bioassayed by the US National Toxicology Program

    SciTech Connect

    Benigni, R.; Andreoli, C.; Zito, R.

    1996-10-01

    Recently the US National Toxicology Program (NTP) sponsored a comparative exercise in which different prediction approaches (both biologically and chemically based) were challenged for their predictive abilities of rodent carcinogenicity of a common set of chemicals. The exercise enjoyed remarkable scientific success and stimulated NTP to sponsor a second challenging round of tests, inviting participants to present predictions relative to the rodent carcinogenicity of a further 30 chemicals; these are currently being tested. In this article, we present our predictions based on structure-activity relationship considerations. In our procedure, first each chemical was assigned to an activity mechanism class and then, with semiquantitative considerations, was assigned a probability carcinogenicity score, taking into account simultaneously the hypothesized action mechanism and physical chemical parameters. 31 refs., 2 tabs.

  11. A framework for predicting impacts on ecosystem services from (sub)organismal responses to chemicals.

    PubMed

    Forbes, Valery E; Salice, Chris J; Birnir, Bjorn; Bruins, Randy J F; Calow, Peter; Ducrot, Virginie; Galic, Nika; Garber, Kristina; Harvey, Bret C; Jager, Henriette; Kanarek, Andrew; Pastorok, Robert; Railsback, Steve F; Rebarber, Richard; Thorbek, Pernille

    2017-04-01

    Protection of ecosystem services is increasingly emphasized as a risk-assessment goal, but there are wide gaps between current ecological risk-assessment endpoints and potential effects on services provided by ecosystems. The authors present a framework that links common ecotoxicological endpoints to chemical impacts on populations and communities and the ecosystem services that they provide. This framework builds on considerable advances in mechanistic effects models designed to span multiple levels of biological organization and account for various types of biological interactions and feedbacks. For illustration, the authors introduce 2 case studies that employ well-developed and validated mechanistic effects models: the inSTREAM individual-based model for fish populations and the AQUATOX ecosystem model. They also show how dynamic energy budget theory can provide a common currency for interpreting organism-level toxicity. They suggest that a framework based on mechanistic models that predict impacts on ecosystem services resulting from chemical exposure, combined with economic valuation, can provide a useful approach for informing environmental management. The authors highlight the potential benefits of using this framework as well as the challenges that will need to be addressed in future work. Environ Toxicol Chem 2017;36:845-859. © 2017 SETAC. © 2017 SETAC.

  12. A framework for predicting impacts on ecosystem services from (sub)organismal responses to chemicals

    DOE PAGES

    Forbes, Valery E.; Salice, Chris J.; Birnir, Bjorn; ...

    2017-03-28

    Protection of ecosystem services is increasingly emphasized as a risk-assessment goal, but there are wide gaps between current ecological risk-assessment endpoints and potential effects on services provided by ecosystems. The authors present a framework that links common ecotoxicological endpoints to chemical impacts on populations and communities and the ecosystem services that they provide. This framework builds on considerable advances in mechanistic effects models designed to span multiple levels of biological organization and account for various types of biological interactions and feedbacks. For illustration, the authors introduce 2 case studies that employ well-developed and validated mechanistic effects models: the inSTREAM individual-basedmore » model for fish populations and the AQUATOX ecosystem model. They also show how dynamic energy budget theory can provide a common currency for interpreting organism-level toxicity. Lastly, they suggest that a framework based on mechanistic models that predict impacts on ecosystem services resulting from chemical exposure, combined with economic valuation, can provide a useful approach for informing environmental management.« less

  13. Sequential chemical extraction for a phosphogypsum environmental impact evaluation

    NASA Astrophysics Data System (ADS)

    Gennari, R. F.; Garcia, I.; Medina, N. H.; Silveira, M. A. G.

    2013-05-01

    Phosphogypsum (PG) is gypsum generated during phosphoric acid production. PG is stocked in large stacks or accumulated in lakes; it contains heavy metals and naturally occurring radioactive elements. The metal contamination may affect the functionality, sustainability and biodiversity of ecosystems. In this work, PG samples were analyzed by Plasma Spectrometry. Total metal content and in the extractable fraction of chemical elements were determined. For K, Ni, Zn, Cr, Cd, Ba, Pb and U, the results obtained are lower than those obtained in a Idaho plant are including and also lower than those found in the soil, indicating this PG sample analyzed probably will not cause any additional metal neither natural radiation contamination.

  14. Evaluation of QSAR models for predicting the partition coefficient (log P) of chemicals under the REACH regulation.

    PubMed

    Cappelli, Claudia Ileana; Benfenati, Emilio; Cester, Josep

    2015-11-01

    The partition coefficient (log P) is a physicochemical parameter widely used in environmental and health sciences and is important in REACH and CLP regulations. In this regulatory context, the number of existing experimental data on log P is negligible compared to the number of chemicals for which it is necessary. There are many models to predict log P and we have selected a number of free programs to examine how they predict the log P of chemicals registered for REACH and to evaluate wheter they can be used in place of experimental data. Some results are good, especially if the information on the applicability domain of the models is considered, with R(2) values from 0.7 to 0.8 and root mean square error (RMSE) from 0.8 to 1.5.

  15. Estimation of Physical Properties and Chemical Reactivity Parameters of Organic Compounds for Environmental Modeling by SPARC

    EPA Science Inventory

    Mathematical models for predicting the transport and fate of pollutants in the environment require reactivity parameter values that is value of the physical and chemical constants that govern reactivity. Although empirical structure activity relationships have been developed th...

  16. Estimation of Physical Properties and Chemical Reactivity Parameters of Organic Compounds for Environmental Modeling by SPARC

    EPA Science Inventory

    Mathematical models for predicting the transport and fate of pollutants in the environment require reactivity parameter values that is value of the physical and chemical constants that govern reactivity. Although empirical structure activity relationships have been developed th...

  17. 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 ...

  18. 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 ...

  19. 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 ...

  20. EPAs ToxCast Program for Predicting Toxcity 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...

  1. 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 ...

  2. 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...

  3. Evaluation of measured and predicted environmental concentrations of selected human pharmaceuticals and personal care products.

    PubMed

    Liebig, Markus; Moltmann, Johann F; Knacker, Thomas

    2006-03-01

    In the past few years, there was an increasing awareness of the occurrence of pharmaceuticals and personal care products (PPCPs) in surface water and drinking water resources, and measurements in surface water, sediment or waste water were done for a number of PPCPs. In the regulatory context, an environmental risk assessment (ERA) has become essential for new PPCPs. Reliably predicted or measured environmental concentrations (PECs or MECs) of chemicals are essential for the exposure assessment, which is one of the two main pillars of environmental risk assessment (ERA). This paper reports on measured data of selected PPCPs in surface waters and compares the measured values with predicted environmental concentrations from exposure models. Such models have been proposed by the European Agency for the Evaluation of Medicinal Products (EMEA) and the Technical Guidance Document on Risk Assessment for New Notified and Existing Chemical Substances (TGD). Four pharmaceuticals and one personal care product were in the scope of the investigation reported here: 17alpha-ethinylestradiol, carbamazepine, sulfamethoxazole and iopromide as well as tonalide. Measured environmental concentrations in surface waters for these PPCPs were reviewed in the scientific literature. The appropriateness of these data was evaluated according to criteria for monitoring data recommended by the TGD. A total of 38 references were evaluated with emphasis on the adequacy of chemical analysis and the representativeness of sampling. Measurements of concentrations in surface water (MECsw), which were found to be adequate for use in exposure assessment according to the monitoring quality criteria, were averaged and compared with respective PECs in surface water (PECsw) derived from exposure modelling (cf. EMEA and TGD). Measured environmental concentrations adequate for use in exposure assessment were found in 20 out of 38 references. Several of the measurements from Germany could be used for a

  4. Metabolism of environmental chemicals by plants - copolymerization into lignin

    SciTech Connect

    Sandermann, H. Jr.; Scheel, D.; Trenck, T.v.d.

    1983-01-01

    Plants have frequently been found to incorporate xenobiotics into ill-defined ''insoluble'' metabolite fractions. Evidence for the lignin nature of such fractions and for the formation of ''insoluble'' metabolite fractions in sterile plant cell cultures is summarized. In several cases, total ''insoluble'' plant metabolite fractions of pesticides were found to be excreted undigested by rats and sheep. Conclusive evidence for covalent incorporation of chemicals into lignin has only recently been obtained. In the case of herbicide 2,4-dichlorophenoxyacetic acid and of the fungicide pentachlorophenol, the derived pesticide/lignin copolymers were characterized by gel permeation chromatography in dimethylformamide, spectral methods, and chemical degradation. In independent studies, artificial lignin was prepared from coniferyl alcohol with the aid of peroxidase/H/sub 2/O/sub 2/. Benzo(..cap alpha..)pyrene quinones and chlorinated anilines could be copolymerized, and the resulting copolymer species were characterized with regard to size distribution and spectral properties. Detailed /sup 1/H- and /sup 13/C-NMR spectroscopic studies showed that a major mechanism of copolymerization of the anilines consisted of a nucleophilic addition to the benzylic ..cap alpha..-carbon of lignol quinone-methide intermediates. In addition, covalent linkages involving the aromatic rings were also formed. 61 references, 3 figures, 4 tables.

  5. Emerging Tools to Estimate and to Predict Exposures to Chemicals

    EPA Science Inventory

    The timely assessment of the human and ecological risk posed by thousands of existing and emerging commercial chemicals is a critical challenge facing EPA in its mission to protect public health and the environment The US EPA has been conducting research to enhance methods used t...

  6. 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...

  7. 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...

  8. Endocrine-disrupting chemicals and oil and natural gas operations: Potential environmental contamination and recommendations to assess complex environmental mixtures

    USGS Publications Warehouse

    Kassotis, Christopher D.; Tillitt, Donald E.; Lin, Chung-Ho; McElroy, Jane A.; Nagel, Susan C.

    2016-01-01

    Background: Hydraulic fracturing technologies, developed over the last 65 years, have only recently been combined with horizontal drilling to unlock oil and gas reserves previously deemed inaccessible. While these technologies have dramatically increased domestic oil and natural gas production, they have also raised concerns for the potential contamination of local water supplies with the approximately 1,000 chemicals used throughout the process, including many known or suspected endocrine-disrupting chemicals.Objectives: We discuss the need for an endocrine component to health assessments for drilling-dense regions in the context of hormonal and anti-hormonal activities for chemicals used.Methods: We discuss the literature on 1) surface and ground water contamination by oil and gas extraction operations, and 2) potential human exposure, particularly in context of the total hormonal and anti-hormonal activities present in surface and ground water from natural and anthropogenic sources, with initial analytical results and critical knowledge gaps discussed.Discussion: In light of the potential for environmental release of oil and gas chemicals that can disrupt hormone receptor systems, we recommend methods for assessing complex hormonally active environmental mixtures.Conclusions: We describe a need for an endocrine-centric component for overall health assessments and provide supporting information that using this may help explain reported adverse health trends as well as help develop recommendations for environmental impact assessments and monitoring programs.

  9. Endocrine-Disrupting Chemicals and Oil and Natural Gas Operations: Potential Environmental Contamination and Recommendations to Assess Complex Environmental Mixtures.

    PubMed

    Kassotis, Christopher D; Tillitt, Donald E; Lin, Chung-Ho; McElroy, Jane A; Nagel, Susan C

    2016-03-01

    Hydraulic fracturing technologies, developed over the last 65 years, have only recently been combined with horizontal drilling to unlock oil and gas reserves previously deemed inaccessible. Although these technologies have dramatically increased domestic oil and natural gas production, they have also raised concerns for the potential contamination of local water supplies with the approximately 1,000 chemicals that are used throughout the process, including many known or suspected endocrine-disrupting chemicals. We discuss the need for an endocrine component to health assessments for drilling-dense regions in the context of hormonal and antihormonal activities for chemicals used. We discuss the literature on a) surface and groundwater contamination by oil and gas extraction operations, and b) potential human exposure, particularly in the context of the total hormonal and antihormonal activities present in surface and groundwater from natural and anthropogenic sources; we also discuss initial analytical results and critical knowledge gaps. In light of the potential for environmental release of oil and gas chemicals that can disrupt hormone receptor systems, we recommend methods for assessing complex hormonally active environmental mixtures. We describe a need for an endocrine-centric component for overall health assessments and provide information supporting the idea that using such a component will help explain reported adverse health trends as well as help develop recommendations for environmental impact assessments and monitoring programs.

  10. Analysis of Environmental Chemical Mixtures and Non-Hodgkin Lymphoma Risk in the NCI-SEER NHL Study

    PubMed Central

    Czarnota, Jenna; Gennings, Chris; Colt, Joanne S.; De Roos, Anneclaire J.; Cerhan, James R.; Severson, Richard K.; Hartge, Patricia; Ward, Mary H.

    2015-01-01

    Background There are several suspected environmental risk factors for non-Hodgkin lymphoma (NHL). The associations between NHL and environmental chemical exposures have typically been evaluated for individual chemicals (i.e., one-by-one). Objectives We determined the association between a mixture of 27 correlated chemicals measured in house dust and NHL risk. Methods We conducted a population-based case–control study of NHL in four National Cancer Institute–Surveillance, Epidemiology, and End Results centers—Detroit, Michigan; Iowa; Los Angeles County, California; and Seattle, Washington—from 1998 to 2000. We used weighted quantile sum (WQS) regression to model the association of a mixture of chemicals and risk of NHL. The WQS index was a sum of weighted quartiles for 5 polychlorinated biphenyls (PCBs), 7 polycyclic aromatic hydrocarbons (PAHs), and 15 pesticides. We estimated chemical mixture weights and effects for study sites combined and for each site individually, and also for histologic subtypes of NHL. Results The WQS index was statistically significantly associated with NHL overall [odds ratio (OR) = 1.30; 95% CI: 1.08, 1.56; p = 0.006; for one quartile increase] and in the study sites of Detroit (OR = 1.71; 95% CI: 1.02, 2.92; p = 0.045), Los Angeles (OR = 1.44; 95% CI: 1.00, 2.08; p = 0.049), and Iowa (OR = 1.76; 95% CI: 1.23, 2.53; p = 0.002). The index was marginally statistically significant in Seattle (OR = 1.39; 95% CI: 0.97, 1.99; p = 0.071). The most highly weighted chemicals for predicting risk overall were PCB congener 180 and propoxur. Highly weighted chemicals varied by study site; PCBs were more highly weighted in Detroit, and pesticides were more highly weighted in Iowa. Conclusions An index of chemical mixtures was significantly associated with NHL. Our results show the importance of evaluating chemical mixtures when studying cancer risk. Citation Czarnota J, Gennings C, Colt JS, De Roos AJ, Cerhan JR, Severson RK, Hartge P, Ward MH

  11. USE OF A CONVECTION-DIFFUSION MODEL TO UNDERSTAND GASTROINTESTINAL ABSORPTION OF ENVIRONMENTALLY-RELEVANT CHEMICALS

    EPA Science Inventory

    Understanding the factors that affect the gastrointestinal absorption of chemicals is important to predicting the delivered systemic dose of chemicals following exposure in food, water, and other media. Two factors of particular interest are the effects of a matrix to which th...

  12. USE OF A CONVECTION-DIFFUSION MODEL TO UNDERSTAND GASTROINTESTINAL ABSORPTION OF ENVIRONMENTALLY-RELEVANT CHEMICALS

    EPA Science Inventory

    Understanding the factors that affect the gastrointestinal absorption of chemicals is important to predicting the delivered systemic dose of chemicals following exposure in food, water, and other media. Two factors of particular interest are the effects of a matrix to which th...

  13. An evaluation of the ability of chemical measurements to predict polycyclic aromatic hydrocarbon-contaminated sediment toxicity to Hyalella azteca.

    PubMed

    McDonough, Kathleen M; Azzolina, Nicholas A; Hawthorne, Steven B; Nakles, David V; Neuhauser, Edward F

    2010-07-01

    The present study examined the ability of three chemical estimation methods to predict toxicity and nontoxicity of polycyclic aromatic hydrocarbon (PAH) -contaminated sediment to the freshwater benthic amphipod Hyalella azteca for 192 sediment samples from 12 field sites. The first method used bulk sediment concentrations of 34 PAH compounds (PAH34), and fraction of total organic carbon, coupled with equilibrium partitioning theory to predict pore-water concentrations (KOC method). The second method used bulk sediment PAH34 concentrations and the fraction of anthropogenic (black carbon) and natural organic carbon coupled with literature-based black carbon-water and organic carbon-water partition coefficients to estimate pore-water concentrations (KOCKBC method). The final method directly measured pore-water concentrations (pore-water method). The U.S. Environmental Protection Agency's hydrocarbon narcosis model was used to predict sediment toxicity for all three methods using the modeled or measured pore-water concentration as input. The KOC method was unable to predict nontoxicity (83% of nontoxic samples were predicted to be toxic). The KOCKBC method was not able to predict toxicity (57% of toxic samples were predicted to be nontoxic) and, therefore, was not protective of the environment. The pore-water method was able to predict toxicity (correctly predicted 100% of the toxic samples were toxic) and nontoxicity (correctly predicted 71% of the nontoxic samples were nontoxic). This analysis clearly shows that direct pore-water measurement is the most accurate chemical method currently available to estimate PAH-contaminated sediment toxicity to H. azteca.

  14. Mutagenesis and differentiation induction in mammalian cells by environmental chemicals

    SciTech Connect

    Friedman, J.; Huberman, E.

    1980-01-01

    These studies indicate that in agreement with the somatic mutation hypothesis, chemical carcinogens: (1) are mutagenic for mammalian cells as tested in the cell-mediated assay; (2) the degree of mutagenicity is correlated with their degree of carcinogenicity; (3) that at least in cases when analyzed carefully the metabolites responsible for mutagenesis are also responsible for initiating the carcinogenic event; and (4) that a cell organ type specificity can be established using the cell-mediated assay. Studies with HL-60 cells and HO melanoma cells and those of others suggest that tumor-promoting phorbol diesters can alter cell differentiation in various cell types and that the degree of the observed alteration in the differentiation properties may be related to the potency of the phorbol esters. Thus these and similar systems may serve as models for both studies and identification of certain types of tumor promoting agents. (ERB)

  15. [The food legislation evaluation of environmental chemicals in freshwater fish].

    PubMed

    Krüger, K E

    1990-07-01

    During the last 1 1/2 decades different regulatory limits have been given to value pollutants in fish under food-legal aspects. Their requested target, which consists of an effective consumer's protection however has been missed by various reasons: The production and distribution of environmental pollutants cannot be suppressed by limits for food. The selective elimination of limit-exceeding individuals from a lot is impossible. Treating both, natural pollutants like geogenic mercury and anthropogenic ones similar seems to be indefensible with regard to food law. Therefore proposals are made to rule only anthropogenic pollutants by law, when regulatory limits are planned to be supplemented. In case of natural distribution less stringent advisory limits seem to be more suitable.

  16. On the Use of Local and Global QSPRs for the Prediction of Physico-chemical Properties of Polybrominated Diphenyl Ethers.

    PubMed

    Papa, Ester; Kovarich, Simona; Gramatica, Paola

    2011-03-14

    Polybrominated diphenyl ethers (PBDEs) are persistent chemicals that have been among the most marketed flame retardants used all over the world in the last decades. PBDEs have been detected in all environmental compartments, as well as in humans and wildlife, where they are able to accumulate and exert their toxic effects. At present only a limited amount of experimental data is available to characterize the physico-chemical and toxicological behavior of PBDEs and similar brominated flame retardants. QSA(P)R approaches are very useful tools to predict missing data starting from the chemical structure of compounds. In this study several local QSPR models, developed specifically for the prediction of logKoa, logKow and melting point of PBDEs, were compared with predictions by global QSPR models, such as KoaWIN, KowWIN and MPBPWIN from the EPI Suite package, and AlogP and MlogP from DRAGON software, which were trained on heterogeneous and large datasets. The analysis addressed in the paper supported the identification of points of strength and weaknesses of both local models, and global models. The results are relevant to support decisions made by general QSAR users and regulators, when they have to select and apply one of the analyzed models to predict properties for PBDEs. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Analysis of baseline gene expression levels from toxicogenomics study control animals to identify sources of variation and predict responses to chemicals

    EPA Science Inventory

    The use of gene expression profiling to predict chemical mode of action would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control ...