Science.gov

Sample records for predicting environmental chemical

  1. 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. PMID:27509301

  2. 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...

  3. 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.

  4. 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...

  5. Predicting environmental chemical factors associated with disease-related gene expression data

    PubMed Central

    2010-01-01

    Background Many common diseases arise from an interaction between environmental and genetic factors. Our knowledge regarding environment and gene interactions is growing, but frameworks to build an association between gene-environment interactions and disease using preexisting, publicly available data has been lacking. Integrating freely-available environment-gene interaction and disease phenotype data would allow hypothesis generation for potential environmental associations to disease. Methods We integrated publicly available disease-specific gene expression microarray data and curated chemical-gene interaction data to systematically predict environmental chemicals associated with disease. We derived chemical-gene signatures for 1,338 chemical/environmental chemicals from the Comparative Toxicogenomics Database (CTD). We associated these chemical-gene signatures with differentially expressed genes from datasets found in the Gene Expression Omnibus (GEO) through an enrichment test. Results We were able to verify our analytic method by accurately identifying chemicals applied to samples and cell lines. Furthermore, we were able to predict known and novel environmental associations with prostate, lung, and breast cancers, such as estradiol and bisphenol A. Conclusions We have developed a scalable and statistical method to identify possible environmental associations with disease using publicly available data and have validated some of the associations in the literature. PMID:20459635

  6. 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

  7. 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.

  8. The prediction of toxic mode of action for environmental pollutants based on physico-chemical properties

    SciTech Connect

    Boxall, A.B.A. |; Watts, C.D.; Bresnen, G.M.; Dearden, J.C.; Scoffin, R.

    1995-12-31

    Aquatic ecosystems receive a wide range of potentially toxic contaminants. One approach to measure the environmental impact of these compounds is to perform costly and detailed experimental investigations. A quick and cost-effective alternative is to predict the likely effects of chemical contaminants using quantitative structure activity relationships (QSARs) which relate effects to chemical structure. One problem with the predictive approach is that QSARs can be established and used only for compounds with a common mode of toxic action. It is therefore important that a compound is assigned to the correct mode of action and that the correct QSAR is used. Two kinds of approach can be used to address this problem. In the first a compound is assigned to a class based on responses observed during experimental tests. The other approach uses chemical structural information e.g. the OECD method where compounds are classed as inert, less inert, reactive or specific acting based on chemical structure. The objective of this study was to determine whether compounds could be classified into one of the four OECD classes solely on the basis of their physico-chemical properties. Approximately 800 compounds were assigned to an OECD class and a range of properties were calculated. Discriminant analysis demonstrated that a large proportion of these compounds could be classified correctly based on two properties, namely a molecular connectivity index ({sup 2}{sub x}) and an electronic parameter (E{sub HOMO}).

  9. 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...

  10. 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...

  11. 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. PMID:25967479

  12. 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

    2016-04-01

    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

  13. 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

  14. 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 ...

  15. 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 ...

  16. 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 ...

  17. 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...

  18. 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

  19. 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...

  20. 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

    2015-02-01

    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.

  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. 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.

  3. Development of an integrated chemical weather prediction system for environmental applications at meso to global scales: NMMB/BSC-CHEM

    NASA Astrophysics Data System (ADS)

    Jorba, O.; Pérez, C.; Karsten, K.; Janjic, Z.; Dabdub, D.; Baldasano, J. M.

    2009-09-01

    This contribution presents the ongoing developments of a new fully on-line chemical weather prediction system for meso to global scale applications. The modeling system consists of a mineral dust module and a gas-phase chemistry module coupled on-line to a unified global-regional atmospheric driver. This approach allows solving small scale processes and their interactions at local to global scales. Its unified environment maintains the consistency of all the physico-chemical processes involved. The atmospheric driver is the NCEP/NMMB numerical weather prediction model (Janjic and Black, 2007) developed at National Centers for Environmental Prediction (NCEP). It represents an evolution of the operational WRF-NMME model extending from meso to global scales. Its unified non-hydrostatic dynamical core supports regional and global simulations. The Barcelona Supercomputing Center is currently designing and implementing a chemistry transport model coupled online with the new global/regional NMMB. The new modeling system is intended to be a powerful tool for research and to provide efficient global and regional chemical weather forecasts at sub-synoptic and mesoscale resolutions. The online coupling of the chemistry follows the approach similar to that of the mineral dust module already coupled to the atmospheric driver, NMMB/BSC-DUST (Pérez et al., 2008). Chemical species are advected and mixed at the corresponding time steps of the meteorological tracers using the same numerical scheme. Advection is eulerian, positive definite and monotone. The chemical mechanism and chemistry solver is based on the Kinetic PreProcessor KPP (Damian et al., 2002) package with the main purpose of maintaining a wide flexibility when configuring the model. Such approach will allow using a simplified chemical mechanism for global applications or a more complete mechanism for high-resolution local or regional studies. Moreover, it will permit the implementation of a specific configuration for

  4. 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.

  5. 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

  6. 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

  7. Environmental and chemical carcinogenesis.

    PubMed

    Wogan, Gerald N; Hecht, Stephen S; Felton, James S; Conney, Allan H; Loeb, Lawrence A

    2004-12-01

    People are continuously exposed exogenously to varying amounts of chemicals that have been shown to have carcinogenic or mutagenic properties in experimental systems. Exposure can occur exogenously when these agents are present in food, air or water, and also endogenously when they are products of metabolism or pathophysiologic states such as inflammation. It has been estimated that exposure to environmental chemical carcinogens may contribute significantly to the causation of a sizable fraction, perhaps a majority, of human cancers, when exposures are related to "life-style" factors such as diet, tobacco use, etc. This chapter summarizes several aspects of environmental chemical carcinogenesis that have been extensively studied and illustrates the power of mechanistic investigation combined with molecular epidemiologic approaches in establishing causative linkages between environmental exposures and increased cancer risks. A causative relationship between exposure to aflatoxin, a strongly carcinogenic mold-produced contaminant of dietary staples in Asia and Africa, and elevated risk for primary liver cancer has been demonstrated through the application of well-validated biomarkers in molecular epidemiology. These studies have also identified a striking synergistic interaction between aflatoxin and hepatitis B virus infection in elevating liver cancer risk. Use of tobacco products provides a clear example of cancer causation by a life-style factor involving carcinogen exposure. Tobacco carcinogens and their DNA adducts are central to cancer induction by tobacco products, and the contribution of specific tobacco carcinogens (e.g. PAH and NNK) to tobacco-induced lung cancer, can be evaluated by a weight of evidence approach. Factors considered include presence in tobacco products, carcinogenicity in laboratory animals, human uptake, metabolism and adduct formation, possible role in causing molecular changes in oncogenes or suppressor genes, and other relevant data

  8. 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...

  9. 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 ...

  10. 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.

  11. 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...

  12. 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.

  13. 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

  14. 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...

  15. 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

  16. 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.

  17. 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...

  18. 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...

  19. 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.

  20. Environmental benefits of chemical propulsion

    SciTech Connect

    Hayes, J.A.; Goldberg, B.E.; Anderson, D.M.

    1995-03-01

    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.

  1. 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.

  2. 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...

  3. 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...

  4. 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),...

  5. Conformal Prediction Classification of a Large Data Set of Environmental Chemicals from ToxCast and Tox21 Estrogen Receptor Assays.

    PubMed

    Norinder, Ulf; Boyer, Scott

    2016-06-20

    Quantitative structure-activity relationships (QSAR) are critical to exploitation of the chemical information in toxicology databases. Exploitation can be extraction of chemical knowledge from the data but also making predictions of new chemicals based on quantitative analysis of past findings. In this study, we analyzed the ToxCast and Tox21 estrogen receptor data sets using Conformal Prediction to enhance the full exploitation of the information in these data sets. We applied aggregated conformal prediction (ACP) to the ToxCast and Tox21 estrogen receptor data sets using support vector machine classifiers to compare overall performance of the models but, more importantly, to explore the performance of ACP on data sets that are significantly enriched in one class without employing sampling strategies of the training set. ACP was also used to investigate the problem of applicability domain using both data sets. Comparison of ACP to previous results obtained on the same data sets using traditional QSAR approaches indicated similar overall balanced performance to methods in which careful training set selections were made, e.g., sensitivity and specificity for the external Tox21 data set of 70-75% and far superior results to those obtained using traditional methods without training set sampling where the corresponding results showed a clear imbalance of 50 and 96%, respectively. Application of conformal prediction to imbalanced data sets facilitates an unambiguous analysis of all data, allows accurate predictive models to be built which display similar accuracy in external validation to external validation, and, most importantly, allows an unambiguous treatment of the applicability domain.

  6. 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...

  7. Impact of Environmental Chemicals on Lung Development

    PubMed Central

    Miller, Mark D.; Marty, Melanie A.

    2010-01-01

    Background Disruption of fundamental biologic processes and associated signaling events may result in clinically significant alterations in lung development. Objectives We reviewed evidence on the impact of environmental chemicals on lung development and key signaling events in lung morphogenesis, and the relevance of potential outcomes to public health and regulatory science. Data sources We evaluated the peer-reviewed literature on developmental lung biology and toxicology, mechanistic studies, and supporting epidemiology. Data synthesis Lung function in infancy predicts pulmonary function throughout life. In utero and early postnatal exposures influence both childhood and adult lung structure and function and may predispose individuals to chronic obstructive lung disease and other disorders. The nutritional and endogenous chemical environment affects development of the lung and can result in altered function in the adult. Studies now suggest that similar adverse impacts may occur in animals and humans after exposure to environmentally relevant doses of certain xenobiotics during critical windows in early life. Potential mechanisms include interference with highly conserved factors in developmental processes such as gene regulation, molecular signaling, and growth factors involved in branching morphogenesis and alveolarization. Conclusions Assessment of environmental chemical impacts on the lung requires studies that evaluate specific alterations in structure or function—end points not regularly assessed in standard toxicity tests. Identifying effects on important signaling events may inform protocols of developmental toxicology studies. Such knowledge may enable policies promoting true primary prevention of lung diseases. Evidence of relevant signaling disruption in the absence of adequate developmental toxicology data should influence the size of the uncertainty factors used in risk assessments. PMID:20444669

  8. WORKSHOP ON ENVIRONMENTALLY CONSCIOUS CHEMICAL PROCESS DESIGN

    EPA Science Inventory

    To encourage the consideration of environmental issues during chemical process design, the USEPA has developed techniques and software tools to evaluate the relative environmental impact of a chemical process. These techniques and tools aid in the risk management process by focus...

  9. 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

  10. 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 ...

  11. 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...

  12. 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. PMID:25679532

  13. 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.

  14. 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...

  15. 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...

  16. Neurogenic inflammation and sensitivity to environmental chemicals.

    PubMed

    Meggs, W J

    1993-08-01

    Neurogenic inflammation as a pathway distinct from antigen-driven, immune-mediated inflammation may play a pivotal role in understanding a broad class of environmental health problems resulting from chemical exposures. Recent progress in understanding the mediators, triggers, and regulation of neurogenic inflammation is reviewed. Evidence for and speculations about a role for neurogenic inflammation in established disorders such as asthma, rhinitis, contact dermatitis, migraine headache, and rheumatoid arthritis are presented. The sick building syndrome and multiple chemical sensitivity syndrome have been defined as clinical entities in which exposure to chemical inhalants gives rise to disease. Current data on the existence of chemical irritant receptors in the airway and skin are discussed; neurogenic inflammation arising from stimulation of chemical irritant receptors is a possible model to explain many of the aspects of chemical sensitivities.

  17. 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.

  18. 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.

  19. INTEGRATING TOXICITY PATHWAY-SPECIFIC IN VITRO TESTING WITH ADVANCED CHEMICAL SELECTION STRATEGIES FOR ENVIRONMENTAL QSAR DEVELOPMENT

    EPA Science Inventory

    Environmental risk assessments often require the evaluation of large numbers of untested chemicals. Chemical assessment protocols that include QSARs have been widely applied for endpoint prediction as well as chemical ranking and prioritization. Approaches are needed to strategi...

  20. Environmental release of chemicals and reproductive ecology.

    PubMed Central

    Bajaj, J S; Misra, A; Rajalakshmi, M; Madan, R

    1993-01-01

    Reproductive ecology is defined as "the study of causes and mechanisms of the effects of environmental risk factors on reproductive health and the methods of their prevention and management." Major areas of concern, within the purview of this paper, relate to adverse pregnancy outcomes, effects on target tissues in the male and the female, and alterations in the control and regulatory mechanisms of reproductive processes. Teratogenic potential of chemicals, released as a result of accidents and catastrophes, is of critical significance. Congenital Minamata disease is due to transplacental fetal toxicity caused by accidental ingestion of methyl mercury. Generalized disorders of ectodermal tissue following prenatal exposure to polychlorinated biphenyls have been reported in Taiwan and Japan. The Bhopal gas disaster, a catastrophic industrial accident, was due to a leak of toxic gas, methyl isocyanate (MIC), in the pesticide manufacturing process. The outcome of pregnancy was studied in female survivors of MIC exposure. The spontaneous abortion rate was nearly four times more common in the affected areas as compared to the control area (24.2% versus 5.6%; p < 0.0001). Furthermore, while stillbirth rate was found to be similar in the affected and control areas, the perinatal and neonatal mortality rates were observed to be higher in the affected area. The rate of congenital malformations in the affected and control areas did not show any significant difference. Chromosomal aberrations and sister chromatid exchange (SCE) frequencies were investigated in human survivors of exposure. The observed SCE frequencies in control and exposed groups indicated that mutagenesis has been induced. Strategies for the management, prediction, and preventability of such disasters are outlined. PMID:8243381

  1. Biomarker strategies to evaluate the environmental effects of chemicals.

    PubMed Central

    Walker, C H

    1998-01-01

    Environmental risk assessment of chemicals depends on the production of toxicity data for surrogate species of mammals, birds, and fish and on making comparisons between these and estimated or predicted environmental concentrations of the chemicals. This paper gives an overview of biomarker assays and strategies that might be used as alternatives, that is, to replace, reduce, or refine currently used ecotoxicity tests that cause suffering to vertebrates. In the present context a biomarker is a biologic response to an environmental chemical at the individual level or below which demonstrates a departure from normal status. Of immediate interest and relevance are nondestructive assays that provide a measure of toxic effect in vertebrate species and that can be used in both laboratory and parallel field studies. A major shortcoming of this approach is that such assays are currently only available for a limited number of chemicals, primarily when the mode of action is known. Nondestructive assays can be performed on blood, skin, excreta, and eggs of birds, fish, reptiles, and amphibians. An interesting recent development is the use of vertebrate cell cultures, including transgenic cell lines that have been developed specifically for toxicity testing. The ultimate concern in ecotoxicology is the effects of chemicals at the level of populations and above. Current risk assessment practices do not address this problem. The development of biomarker strategies could be part of a movement toward more ecologic end points in the safety evaluation of chemicals, which would effect a reduction in animal tests that cause suffering. PMID:9599708

  2. 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

    2014-11-01

    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.

  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. 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).

  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. 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 ...

  7. Predicting modes of toxic action from chemical structure: an overview.

    PubMed

    Bradbury, S P

    1994-01-01

    In the field of environmental toxicology, and especially aquatic toxicology, quantitative structure activity relationships (QSARs) have developed as scientifically-credible tools for predicting the toxicity of chemicals when little or no empirical data are available. A basic and fundamental understanding of toxicological principles has been considered crucial to the continued acceptance and application of these techniques as biologically relevant. As a consequence, there has been an evolution of QSAR development and application from that of a chemical-class perspective to one that is more consistent with assumptions regarding modes of toxic action. The assessment of a compound's likely mode of toxic action is critical for a correct QSAR selection; incorrect mode of action-based QSAR selections can result in 10- to 1000-fold errors in toxicity predictions. The establishment of toxicologically-credible techniques to assess mode of toxic action from chemical structure requires toxicodynamic knowledge bases that are clearly defined with regard to exposure regimes and biological models/endpoints and based on compounds that adequately span the diversity of chemicals anticipated for future applications. With such knowledge bases classification systems, including rule-based experts systems, have been established for use in predictive aquatic toxicology applications. PMID:8790641

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

    EPA Science Inventory

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

  9. 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. PMID:15646185

  10. 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

  11. 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...

  12. 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

  13. Influences of Environmental Chemicals on Atopic Dermatitis.

    PubMed

    Kim, Kwangmi

    2015-06-01

    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.

  14. Computational Molecular Modeling for Evaluating the Toxicity of Environmental Chemicals: Prioritizing Bioassay Requirements

    EPA Science Inventory

    This commentary provides an overview of the challenges that arise from applying molecular modeling tools developed and commonly used for pharmaceutical discovery to the problem of predicting the potential toxicities of environmental chemicals.

  15. 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

  16. 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.

  17. 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. PMID:14594379

  18. 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).

  19. 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. PMID:19830747

  20. 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.

  1. 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. ...

  2. 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...

  3. Predicting Tick Presence by Environmental Risk Mapping

    PubMed Central

    Swart, Arno; Ibañez-Justicia, Adolfo; Buijs, Jan; van Wieren, Sip E.; Hofmeester, Tim R.; Sprong, Hein; Takumi, Katsuhisa

    2014-01-01

    Public health statistics recorded an increasing trend in the incidence of tick bites and erythema migrans (EM) in the Netherlands. We investigated whether the disease incidence could be predicted by a spatially explicit categorization model, based on environmental factors and a training set of tick absence–presence data. Presence and absence of Ixodes ricinus were determined by the blanket-dragging method at numerous sites spread over the Netherlands. The probability of tick presence on a 1 km by 1 km square grid was estimated from the field data using a satellite-based methodology. Expert elicitation was conducted to provide a Bayesian prior per landscape type. We applied a linear model to test for a linear relationship between incidence of EM consultations by general practitioners in the Netherlands and the estimated probability of tick presence. Ticks were present at 252 distinct sampling coordinates and absent at 425. Tick presence was estimated for 54% of the total land cover. Our model has predictive power for tick presence in the Netherlands, tick-bite incidence per municipality correlated significantly with the average probability of tick presence per grid. The estimated intercept of the linear model was positive and significant. This indicates that a significant fraction of the tick-bite consultations could be attributed to the I. ricinus population outside the resident municipality. PMID:25505781

  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. 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…

  6. 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...

  7. Human metabolic interactions of environmental chemicals.

    PubMed

    Hodgson, Ernest; Rose, Randy L

    2007-01-01

    Investigations utilizing recombinant human xenobiotic-metabolizing enzymes as well as human hepatocytes have revealed a number of interactions not only between different environmental chemicals (ECs) but also between ECs and endogenous metabolites. Organophosphorus insecticides (OPs) are potent inhibitors of the human metabolism of carbaryl, carbofuran, DEET and fipronil, as well as the jet fuel components, nonane and naphthalene. OPs are potent irreversible inhibitors of testosterone metabolism by cytochrome P450 (CYP) 3A4 and of estradiol metabolism by CYP3A4 and CYP1A2. All of these CYP inhibitions are believed to be due to the release of reactive sulfur during CYP-catalyzed oxidative desulfuration. It has also been shown that the esterase(s) responsible for the initial step in permethrin metabolism in human liver is inhibited by both chlorpyrifos oxon and carbaryl. A number of pesticides, including chlorpyrifos, fipronil and permethrin, and the repellent, DEET, have been shown to be inducers of CYP isoforms in human hepatocytes, with fipronil being the most potent. Several agrochemicals, including fipronil and the pyrethroids, permethrin and deltamethrin, show toxicity toward human hepatocytes with fipronil being the most potent in this regard. Endosulfan-alpha, which has shown promise as a model substrate for phenotyping CYP3A4 and CYP2B6 in human liver microsomes, is also an inducer of CYP2B6, acting through the PXR receptor.

  8. Environmental applications of chemically pure natural ferrihydrite.

    PubMed

    Filip, Jan; Zboril, Radek; Schneeweiss, Oldrich; Zeman, Josef; Cernik, Miroslav; Kvapil, Petr; Otyepka, Michal

    2007-06-15

    Fresh precipitates, deposited from seepage waters of complex-ore mine-tailing impoundment at Zlaté Hory, Czech Republic, were characterized by means of X-ray diffraction, transmission electron microscopy, low temperature and in-field Mössbauer spectroscopy, and Brunauer-Emmett-Teller surface area measurements. The prevailing phases (approximately 96 wt %) found in precipitates are poorly crystalline, 2-6 nm sized two-line ferrihydrite, forming globular aggregates of about 150 nm in diameter, rimmed by acicular irregular nanocrystals of goethite. These nanocrystalline ferrihydrite-goethite precipitates are of a relatively high chemical purity (approximately 3% SiO2, Zn approximately 1300 ppm, trace and rare earth elements < 100 ppm) and thus applicable in various nanotechnologies. With a surface area of 270 m2 g(-1), precipitate possesses a high catalytic activity in the decomposition of hydrogen peroxide, which is comparable with that found for commercially accessible FeO(OH) catalyst. Another superior aspect of such natural nanoparticles presents a cheap and suitable precursor for a thermally induced solid-state synthesis of the stable core-shell alpha-Fe-FeO nanoparticles that are well applicable in reductive technologies of groundwater treatment. Just the possibility of using the undesirable waste contaminating the environment in further environmental technologies is the key practical benefit discussed in this paper.

  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. 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.

  11. Prediction of chemical biotransfer of organic chemicals from cattle diet into beef and milk using the molecular connectivity index

    SciTech Connect

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

    1996-03-01

    Biotransfer factors (BTFs) represent the ratio of the concentration of a chemical found in animal tissues such as beef or milk to the animal`s daily intake of that chemical. Using currently available citations for BTFs in meat and milk, the use of molecular connectivity indices (MCIs) as a quantitative structure reactivity relationship (QSAR) for predicting the BTFs for organic chemicals is evaluated. Based on a statistical evaluation of correlation, residual error, and cross validation, this evaluation reveals that the MCI provides both higher reliability and a fast and cost-effective method for predicting the potential biotransfer of a chemical from environmental media into food. When compared to the use of K{sub ow} as a predictor of BTFs, the analysis here indicates that MCI can substantially increase the reliability with which BTFs can be estimated. 66 refs., 2 figs., 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. 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. 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...

  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. 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

  17. 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.

  18. 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...

  19. 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.

  20. 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...

  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 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.

  3. 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...

  4. 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...

  5. 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 ...

  6. 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.

  7. 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...

  8. 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...

  9. 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...

  10. Information System for Environmental Chemicals: Training for End Users.

    ERIC Educational Resources Information Center

    Voigt, Kristina; And Others

    1991-01-01

    Discusses factors to consider in identifying and accessing appropriate data sources for environmental chemical information and describes three training programs for end-users: (1) a course on retrieval of information on dangerous substances; (2) a seminar on German offline databases on chemicals; and (3) a workshop on the Information System for…

  11. Estimation of environmentally relevant chemical properties of veterinary ionophore antibiotics.

    PubMed

    Sun, Peizhe; Pavlostathis, Spyros G; Huang, Ching-Hua

    2016-09-01

    Monensin (MON) and salinomycin (SAL), known as polyether ionophore antibiotics (IPAs), are extensively used in livestock industry and can enter the environment via animal manure and agricultural runoff. Although some studies have investigated the environmental fate and transformation of IPAs, the lack of information on IPAs' aqueous-phase chemical properties is a major hindrance for further in-depth research. This study was able to experimentally determine the acidity constants (pKa), metal-complex dissociation constants (Kdiss), and intrinsic aqueous solubility of MON species, and some of these properties of SAL. The pKa value of MON was found to be 4.5, close to other aliphatic carboxylic acids and the predicted value by the computer program ChemAxon. The metal-complex dissociation constants of MON were estimated to be 0.058 and 0.573 with sodium ion (Na(+)) and potassium ion (K(+)), respectively. The Kdiss value of SAL with sodium ion was found to be 1.31. Compared to the previous values determined in organic solvents, the Kdiss of MON in aqueous phase are several orders of magnitude higher but maintain the same relative selectivity toward metal ions (Na(+) versus K(+)). The determined pKa and Kdiss values were also used to assess the aqueous solubility limits of different IPA species under different pH and metal ion concentrations. Results from this study provide more accurate information for the properties of IPAs. The obtained constants can be applied to predict the speciation of IPAs in various aquatic systems and help shed light on the environmental fate of IPAs. PMID:27282367

  12. Estimation of environmentally relevant chemical properties of veterinary ionophore antibiotics.

    PubMed

    Sun, Peizhe; Pavlostathis, Spyros G; Huang, Ching-Hua

    2016-09-01

    Monensin (MON) and salinomycin (SAL), known as polyether ionophore antibiotics (IPAs), are extensively used in livestock industry and can enter the environment via animal manure and agricultural runoff. Although some studies have investigated the environmental fate and transformation of IPAs, the lack of information on IPAs' aqueous-phase chemical properties is a major hindrance for further in-depth research. This study was able to experimentally determine the acidity constants (pKa), metal-complex dissociation constants (Kdiss), and intrinsic aqueous solubility of MON species, and some of these properties of SAL. The pKa value of MON was found to be 4.5, close to other aliphatic carboxylic acids and the predicted value by the computer program ChemAxon. The metal-complex dissociation constants of MON were estimated to be 0.058 and 0.573 with sodium ion (Na(+)) and potassium ion (K(+)), respectively. The Kdiss value of SAL with sodium ion was found to be 1.31. Compared to the previous values determined in organic solvents, the Kdiss of MON in aqueous phase are several orders of magnitude higher but maintain the same relative selectivity toward metal ions (Na(+) versus K(+)). The determined pKa and Kdiss values were also used to assess the aqueous solubility limits of different IPA species under different pH and metal ion concentrations. Results from this study provide more accurate information for the properties of IPAs. The obtained constants can be applied to predict the speciation of IPAs in various aquatic systems and help shed light on the environmental fate of IPAs.

  13. 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...

  14. 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...

  15. Structure-activity relationships: quantitative techniques for predicting the behavior of chemicals in the ecosystem

    SciTech Connect

    Nirmalakhandan, N.; Speece, R.E.

    1988-06-01

    Quantitative Structure-Activity Relationships (QSARs) are used increasingly to screen and predict the toxicity and the fate of chemicals released into the environment. The impetus to use QSAR methods in this area has been the large number of synthetic chemicals introduced into the ecosystem via intensive agriculture and industrialization. Because of the costly and time-consuming nature of environmental fate testing, QSARs have been effectively used to screen large classes of chemical compounds and flag those that appear to warrant more thorough testing.

  16. 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

  17. 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...

  18. Evaluating Geographically Weighted Regression Models for Environmental Chemical Risk Analysis

    PubMed Central

    Czarnota, Jenna; Wheeler, David C; Gennings, Chris

    2015-01-01

    In the evaluation of cancer risk related to environmental chemical exposures, the effect of many correlated chemicals on disease is often of interest. The relationship between correlated environmental chemicals and health effects is not always constant across a study area, as exposure levels may change spatially due to various environmental factors. Geographically weighted regression (GWR) has been proposed to model spatially varying effects. However, concerns about collinearity effects, including regression coefficient sign reversal (ie, reversal paradox), may limit the applicability of GWR for environmental chemical risk analysis. A penalized version of GWR, the geographically weighted lasso, has been proposed to remediate the collinearity effects in GWR models. Our focus in this study was on assessing through a simulation study the ability of GWR and GWL to correctly identify spatially varying chemical effects for a mixture of correlated chemicals within a study area. Our results showed that GWR suffered from the reversal paradox, while GWL overpenalized the effects for the chemical most strongly related to the outcome. PMID:25983546

  19. 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.

  20. Prediction uncertainty of environmental change effects on temperate European biodiversity.

    PubMed

    Dormann, Carsten F; Schweiger, Oliver; Arens, P; Augenstein, I; Aviron, St; Bailey, Debra; Baudry, J; Billeter, R; Bugter, R; Bukácek, R; Burel, F; Cerny, M; Cock, Raphaël De; De Blust, Geert; DeFilippi, R; Diekötter, Tim; Dirksen, J; Durka, W; Edwards, P J; Frenzel, M; Hamersky, R; Hendrickx, Frederik; Herzog, F; Klotz, St; Koolstra, B; Lausch, A; Le Coeur, D; Liira, J; Maelfait, J P; Opdam, P; Roubalova, M; Schermann-Legionnet, Agnes; Schermann, N; Schmidt, T; Smulders, M J M; Speelmans, M; Simova, P; Verboom, J; van Wingerden, Walter; Zobel, M

    2008-03-01

    Observed patterns of species richness at landscape scale (gamma diversity) cannot always be attributed to a specific set of explanatory variables, but rather different alternative explanatory statistical models of similar quality may exist. Therefore predictions of the effects of environmental change (such as in climate or land cover) on biodiversity may differ considerably, depending on the chosen set of explanatory variables. Here we use multimodel prediction to evaluate effects of climate, land-use intensity and landscape structure on species richness in each of seven groups of organisms (plants, birds, spiders, wild bees, ground beetles, true bugs and hoverflies) in temperate Europe. We contrast this approach with traditional best-model predictions, which we show, using cross-validation, to have inferior prediction accuracy. Multimodel inference changed the importance of some environmental variables in comparison with the best model, and accordingly gave deviating predictions for environmental change effects. Overall, prediction uncertainty for the multimodel approach was only slightly higher than that of the best model, and absolute changes in predicted species richness were also comparable. Richness predictions varied generally more for the impact of climate change than for land-use change at the coarse scale of our study. Overall, our study indicates that the uncertainty introduced to environmental change predictions through uncertainty in model selection both qualitatively and quantitatively affects species richness projections. PMID:18070098

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Generalized Concentration Addition Modeling Predicts Mixture Effects of Environmental PPARγ Agonists.

    PubMed

    Watt, James; Webster, Thomas F; Schlezinger, Jennifer J

    2016-09-01

    The vast array of potential environmental toxicant combinations necessitates the development of efficient strategies for predicting toxic effects of mixtures. Current practices emphasize the use of concentration addition to predict joint effects of endocrine disrupting chemicals in coexposures. Generalized concentration addition (GCA) is one such method for predicting joint effects of coexposures to chemicals and has the advantage of allowing for mixture components to have differences in efficacy (ie, dose-response curve maxima). Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that plays a central role in regulating lipid homeostasis, insulin sensitivity, and bone quality and is the target of an increasing number of environmental toxicants. Here, we tested the applicability of GCA in predicting mixture effects of therapeutic (rosiglitazone and nonthiazolidinedione partial agonist) and environmental PPARγ ligands (phthalate compounds identified using EPA's ToxCast database). Transcriptional activation of human PPARγ1 by individual compounds and mixtures was assessed using a peroxisome proliferator response element-driven luciferase reporter. Using individual dose-response parameters and GCA, we generated predictions of PPARγ activation by the mixtures, and we compared these predictions with the empirical data. At high concentrations, GCA provided a better estimation of the experimental response compared with 3 alternative models: toxic equivalency factor, effect summation and independent action. These alternatives provided reasonable fits to the data at low concentrations in this system. These experiments support the implementation of GCA in mixtures analysis with endocrine disrupting compounds and establish PPARγ as an important target for further studies of chemical mixtures.

  6. 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.

  7. 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.

  8. Macromolecular adducts caused by environmental chemicals.

    PubMed

    Neumann, H G; Albrecht, O; van Dorp, C; Zwirner-Baier, I

    1995-12-01

    We describe three biomonitoring studies in which hemoglobin (Hb) adducts were used as biochemical markers to assess indirectly the target dose of genotoxic chemicals. We monitored the exposure to 1,3-butadiene in occupationally exposed workers and in two control groups by analyzing the adducts formed by the reaction of the first activation product, butadiene monoepoxide, with the terminal valine of Hb; we also measured hydrolyzable adducts formed by the reaction of metabolically formed nitroso derivatives with Hb from five selected nitropolycyclic aromatic hydrocarbons (1-nitropyrene; 2-nitrofluorene, 3-nitrofluoranthrene, 6-nitrochrysene, and 9-nitrophenanthrene) in coke oven workers of different job categories and control workers of the same geographical area. We detected hydrolyzable adducts from monocyclic nitroarenes in blood from individuals living in a contaminated area where explosives had been produced and from controls. The contaminants considered were 2,4,6-trinitrotoluene; 2,4- and 2,6-dinitrotoluene; and 1,3-dinitrobenzene. Differences between groups were significant, but interindividual variation was great and back-ground exposures must be considered.

  9. 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.

  10. 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

  11. Thyroid hormone metabolism and environmental chemical exposure

    PubMed Central

    2012-01-01

    Background Polychlorinated dioxins and –furans (PCDD/Fs) and polychlorinated-biphenyls (PCBs) are environmental toxicants that have been proven to influence thyroid metabolism both in animal studies and in human beings. In recent years polybrominated diphenyl ethers (PBDEs) also have been found to have a negative influence on thyroid hormone metabolism. The lower brominated flame retardants are now banned in the EU, however higher brominated decabromo-diphenyl ether (DBDE) and the brominated flame retardant hexabromocyclododecane (HBCD) are not yet banned. They too can negatively influence thyroid hormone metabolism. An additional brominated flame retardant that is still in use is tetrabromobisphenol-A (TBBPA), which has also been shown to influence thyroid hormone metabolism. Influences of brominated flame retardants, PCDD/F’s and dioxin like-PCBs (dl-PCB’s) on thyroid hormone metabolism in adolescence in the Netherlands will be presented in this study and determined if there are reasons for concern to human health for these toxins. In the period 1987-1991, a cohort of mother-baby pairs was formed in order to detect abnormalities in relation to dioxin levels in the perinatal period. The study demonstrated that PCDD/Fs were found around the time of birth, suggesting a modulation of the setpoint of thyroid hormone metabolism with a higher 3,3’, 5,5’tetrathyroxine (T4) levels and an increased thyroid stimulating hormone (TSH). While the same serum thyroid hormone tests (- TSH and T4) were again normal by 2 years of age and were still normal at 8-12 years, adolescence is a period with extra stress on thyroid hormone metabolism. Therefore we measured serum levels of TSH, T4, 3,3’,5- triiodothyronine (T3), free T4 (FT4), antibodies and thyroxine-binding globulin (TBG) in our adolescent cohort. Methods Vena puncture was performed to obtain samples for the measurement of thyroid hormone metabolism related parameters and the current serum dioxin (PCDD/Fs), PCB

  12. 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. PMID:27513554

  13. 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.

  14. 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...

  15. 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

  16. 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.

  17. 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. PMID:27401018

  18. Environmental sentinel biomonitors: integrated response systems for monitoring toxic chemicals

    NASA Astrophysics Data System (ADS)

    van der Schalie, William H.; Reuter, Roy; Shedd, Tommy R.; Knechtges, Paul L.

    2002-02-01

    Operational environments for military forces are becoming potentially more dangerous due to the increased number, use, and misuse of toxic chemicals across the entire range of military missions. Defense personnel may be exposed to harmful chemicals as a result of industrial accidents or intentional or unintentional action of enemy, friendly forces, or indigenous populations. While there has been a significant military effort to enable forces to operate safely and survive and sustain operations in nuclear, biological, chemical warfare agent environments, until recently there has not been a concomitant effort associated with potential adverse health effects from exposures of deployed personnel to toxic industrial chemicals. To provide continuous real-time toxicity assessments across a broad spectrum of individual chemicals or chemical mixtures, an Environmental Sentinel Biomonitor (ESB) system concept is proposed. An ESB system will integrate data from one or more platforms of biologically-based systems and chemical detectors placed in the environment to sense developing toxic conditions and transmit time-relevant data for use in risk assessment, mitigation, and/or management. Issues, challenges, and next steps for the ESB system concept are described, based in part on discussions at a September 2001 workshop sponsored by the U.S. Army Center for Environmental Health Research.

  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 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.

  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

    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.

  2. 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...

  3. 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 ...

  4. 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

  5. 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.

  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. Facing environmental predictability with different sources of epigenetic variation.

    PubMed

    Leung, Christelle; Breton, Sophie; Angers, Bernard

    2016-08-01

    Different sources of epigenetic changes can increase the range of phenotypic options. Environmentally induced epigenetic changes and stochastic epimutations are, respectively, associated with phenotypic plasticity and diversifying bet-hedging. Their relative contribution is thus expected to reflect the capacity of a genotype to face distinct changes since these strategies are differentially selected according to environmental uncertainty. To test this hypothesis, we assessed the sources of epigenetic changes on clonal fish from predictable (lakes) or unpredictable (intermittent streams) environments. DNA methylation of clones from natural conditions revealed contrasting contribution of environmentally induced versus stochastic changes according to their origins. These differences were validated in common garden experiments. Consistent with theoretical models, distinct sources of epigenetic variation prevail according to the environmental uncertainty. However, both sources act conjointly, suggesting that plasticity and random processes are complementary strategies. This represents a rigorous approach for further exploring the capacity of organisms to respond to environmental conditions. PMID:27551379

  8. 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

  9. 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.

  10. Agricultural chemical application practices to reduce environmental contamination.

    PubMed

    Bode, L E

    1990-01-01

    Current practices of applying agricultural chemicals play a major role in the environmental health concerns of agriculture. Those who mix, load, and handle the concentrated formulations run the greatest risk of exposure but field hands and others can encounter significant levels of pesticides. Drift can be a major source of contamination to residents, wildlife, and water sources. Improved methods of application and ways of reducing the total amount of pesticide applied can help reduce environmental contamination. Chemigation, direct injection, closed system handling, and fertilizer impregnation are examples of technology that affect the efficiency of applying agricultural chemicals. An area of beneficial research is related to leak and spill technology. Current surveys indicate that point sources such as spills, mixing and loading areas, back-siphoning, and direct routes for surface water movement into the ground are often a major cause of pesticides reaching groundwater. The commercial dealer/applicator provides storage, handling, mixing, and loading for large amounts of chemicals and has received limited guidance regarding the products. Education remains an important element of any rural environmental health strategy. With appropriate information about pesticide risks and groundwater, people will be better equipped to address environmental concerns. By design, agricultural chemicals are biologically active and, in most cases, toxic. Thus, they pose potential risks to humans, wildlife, water, and the environment in general. The magnitude of the risks depends to some degree on the methods and techniques used to apply the chemicals. Pesticides are applied by persons possessing a variety of skills, using equipment ranging from hand-operated systems to aircraft.

  11. 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,…

  12. 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.

  13. Rapid screening of environmental chemicals for estrogen receptor binding capacity.

    PubMed Central

    Bolger, R; Wiese, T E; Ervin, K; Nestich, S; Checovich, W

    1998-01-01

    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 chemicals. While it is clear that in vivo methods will be required to identify adverse effects produced by these chemicals, in vitro assays can define particular mechanisms of action and have the potential to be employed as rapid and low-cost screens for use in large scale EDC screening programs. Traditional estrogen receptor (ER) binding assays are useful for characterizing a chemical's potential to be an estrogen-acting EDC, but they involve displacement of a radioactive ligand from crude receptor preparations at low temperatures. The usefulness of these assays for realistically determining the ER binding interactions of weakly estrogenic environmental and industrial compounds that have low aqueous solubility is unclear. In this report, we present a novel fluorescence polarization (FP) method that measures the capacity of a competitor chemical to displace a high affinity fluorescent ligand from purified, recombinant human ER-[alpha] at room temperature. The ER-[alpha] binding interactions generated for 15 natural and synthetic compounds were found to be similar to those determined with traditional receptor binding assays. We also discuss the potential to employ this FP technology to binding studies involving ER-ss and other receptors. Thus, the assay introduced in this study is a nonradioactive receptor binding method that shows promise as a high throughput screening method for large-scale testing of environmental and industrial chemicals for ER binding interactions. Images Figure 2 Figure 3 Figure 4 PMID:9721254

  14. 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.

  15. [The pattern of variables predicting self-reported environmental behavior].

    PubMed

    Kannapin, O; Pawlik, K; Zinn, F

    1998-01-01

    Many of the changes observed in our environment today may be traced back to human action. In addition to a descriptive elaboration of possible predictor variables, the psychological analysis of environmental behavior is directed towards the identification of key variables and the structural relationships among these and behavior. Variables that are suitable to predict environmental behavior need to be identified. In this study, 215 subjects each were drawn from an urban and a rural sample; 85 further subjects were considered to be highly environmentally engaged. Thus the total sample population for this study included 515 subjects. Scales on acquisition of information, values, locus of control, attribution of responsibility, and environmental threat were administered to all subjects. A modified version of the protection-motivation theory formulated by Gardner and Stern (1996) served as a reference model. Simultaneous regression analysis revealed that scales specifically directed to the domain of environmental behavior are well suited to explain environmental actions, especially in the subset of highly engaged persons (R2 = .58). In contrast to both other groups, the acquisition of environmentally specific information was a strong predictor in this group. On the basis of these regression analyses, it is argued that additional predictors--along with the ones used in this study--must be taken into account in groups that do not display extraordinary engagement in environmental matters.

  16. 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.

  17. Bioassay-directed chemical analysis in environmental research

    SciTech Connect

    Schuetzle, D.; Lewtas, J.

    1986-01-01

    The use of short-term bioassay tests in conjunction with analytical measurements, constitute a powerful tool for identifying important environmental contaminants. The authors have coined the terminology bioassay directed chemical analysis to best describe this marriage of analytical chemistry and biology. The objective of this methodology is to identify key compounds in various types of air-pollutant samples. Once that task is completed, studies on metabolism, sources, environmental exposure and atmospheric chemistry can be undertaken. The principles and methodologies for bioassay directed chemical analysis are presented and illustrated in this paper. Most of this work has been directed toward the characterization of ambient air and diesel particulates, which are used as examples in this report to illustrate the analytical logic used for identifying the bio-active components of complex mixtures.

  18. Predicting microbial toxicity of nonuniform multicomponent mixtures of organic chemicals

    SciTech Connect

    Peace, J.; Daniel, D.; Nirmalakhandan, N.; Egemen, E.

    1997-04-01

    Three schemes proposed in the literature for analyzing joint toxic effects of multicomponent mixtures on fish, namely the additivity index (AI), the mixture toxicity index (MTI), and the similarity parameter ({lambda}) are evaluated in this study for microbial toxicity. A new approach is proposed to establish acceptance limits for the similarity parameter, {lambda}, based on experimental errors and uncertainties. Quantitative structure activity relationship (QSAR) techniques are then used to develop a model to predict the concentrations of components in mixtures that would jointly cause 50% inhibition of microbial respiration. The application of this approach is demonstrated on the experimental toxicity data of six eight-component organic chemical mixtures on microorganisms.

  19. 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

  20. Environmental monitoring of hydrocarbons: a chemical sensor perspective.

    PubMed

    Pejcic, Bobby; Eadington, Peter; Ross, Andrew

    2007-09-15

    Assessing the environmental impact of organic pollutants requires reliable analytical tools that can rapidly screen them with minimal sample handling. Chemical sensors are expected to play an increasing role in environmental monitoring, and recent technological advances are certain to facilitate the application of chemical sensing devices. The search for highly selective, sensitive, low cost, stable, and robust sensors for hydrocarbons is an area of interest that is reflected by many publications on this topic. This report surveys some of the work that has been undertaken using sensors to detect hydrocarbons in the gas and liquid phase. The analytical capabilities of various sensors are compared and discussed in terms of their selectivity, sensitivity, and detection limit. It was found that the sensitivity is highly dependent on the experimental conditions used in the preparation of the sensing surface. Many sensors display acceptable sensitivity under controlled laboratory conditions; however, very few are selective enough to distinguish among several hydrocarbons in complex mixtures. Selectivity is still a challenge that is hindering the widespread application of chemical sensors for environmental monitoring of hydrocarbons and a number of strategies have been proposed to help overcome some of these problems.

  1. 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

  2. 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.

  3. Generalized Concentration Addition Modeling Predicts Mixture Effects of Environmental PPARγ Agonists.

    PubMed

    Watt, James; Webster, Thomas F; Schlezinger, Jennifer J

    2016-09-01

    The vast array of potential environmental toxicant combinations necessitates the development of efficient strategies for predicting toxic effects of mixtures. Current practices emphasize the use of concentration addition to predict joint effects of endocrine disrupting chemicals in coexposures. Generalized concentration addition (GCA) is one such method for predicting joint effects of coexposures to chemicals and has the advantage of allowing for mixture components to have differences in efficacy (ie, dose-response curve maxima). Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that plays a central role in regulating lipid homeostasis, insulin sensitivity, and bone quality and is the target of an increasing number of environmental toxicants. Here, we tested the applicability of GCA in predicting mixture effects of therapeutic (rosiglitazone and nonthiazolidinedione partial agonist) and environmental PPARγ ligands (phthalate compounds identified using EPA's ToxCast database). Transcriptional activation of human PPARγ1 by individual compounds and mixtures was assessed using a peroxisome proliferator response element-driven luciferase reporter. Using individual dose-response parameters and GCA, we generated predictions of PPARγ activation by the mixtures, and we compared these predictions with the empirical data. At high concentrations, GCA provided a better estimation of the experimental response compared with 3 alternative models: toxic equivalency factor, effect summation and independent action. These alternatives provided reasonable fits to the data at low concentrations in this system. These experiments support the implementation of GCA in mixtures analysis with endocrine disrupting compounds and establish PPARγ as an important target for further studies of chemical mixtures. PMID:27255385

  4. Modeling Nonlinear Adsorption with a Single Chemical Parameter: Predicting Chemical Median Langmuir Binding Constants.

    PubMed

    Davis, Craig Warren; Di Toro, Dominic M

    2015-07-01

    Procedures for accurately predicting linear partition coefficients onto various sorbents (e.g., organic carbon, soils, clay) are reliable and well established. However, similar procedures for the prediction of sorption parameters of nonlinear isotherm models are not. The purpose of this paper is to present a procedure for predicting nonlinear isotherm parameters, specifically the median Langmuir binding constants, K̃L, obtained utilizing the single-chemical parameter log-normal Langmuir isotherm developed in the accompanying work. A reduced poly parameter linear free energy relationship (pp-LFER) is able to predict median Langmuir binding constants for graphite, charcoal, and Darco granular activated carbon (GAC) adsorption data. For the larger F400 GAC data set, a single pp-LFER model was insufficient, as a plateau is observed for the median Langmuir binding constants of larger molecular volume sorbates. This volumetric cutoff occurs in proximity to the median pore diameter for F400 GAC. A log-linear relationship exists between the aqueous solubility of these large compounds and their median Langmuir binding constants. Using this relationship for the chemicals above the volumetric cutoff and the pp-LFER below the cutoff, the median Langmuir binding constants can be predicted with a root-mean square error for graphite (n = 13), charcoal (n = 11), Darco GAC (n = 14), and F400 GAC (n = 44) of 0.129, 0.307, 0.407, and 0.424, respectively. PMID:26035017

  5. Modeling Nonlinear Adsorption with a Single Chemical Parameter: Predicting Chemical Median Langmuir Binding Constants.

    PubMed

    Davis, Craig Warren; Di Toro, Dominic M

    2015-07-01

    Procedures for accurately predicting linear partition coefficients onto various sorbents (e.g., organic carbon, soils, clay) are reliable and well established. However, similar procedures for the prediction of sorption parameters of nonlinear isotherm models are not. The purpose of this paper is to present a procedure for predicting nonlinear isotherm parameters, specifically the median Langmuir binding constants, K̃L, obtained utilizing the single-chemical parameter log-normal Langmuir isotherm developed in the accompanying work. A reduced poly parameter linear free energy relationship (pp-LFER) is able to predict median Langmuir binding constants for graphite, charcoal, and Darco granular activated carbon (GAC) adsorption data. For the larger F400 GAC data set, a single pp-LFER model was insufficient, as a plateau is observed for the median Langmuir binding constants of larger molecular volume sorbates. This volumetric cutoff occurs in proximity to the median pore diameter for F400 GAC. A log-linear relationship exists between the aqueous solubility of these large compounds and their median Langmuir binding constants. Using this relationship for the chemicals above the volumetric cutoff and the pp-LFER below the cutoff, the median Langmuir binding constants can be predicted with a root-mean square error for graphite (n = 13), charcoal (n = 11), Darco GAC (n = 14), and F400 GAC (n = 44) of 0.129, 0.307, 0.407, and 0.424, respectively.

  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. Potential effects of environmental chemical contamination in congenital heart disease.

    PubMed

    Gorini, Francesca; Chiappa, Enrico; Gargani, Luna; Picano, Eugenio

    2014-04-01

    There is compelling evidence that prenatal exposures to environmental xenobiotics adversely affect human development and childhood. Among all birth defects, congenital heart disease (CHD) is the most prevalent of all congenital malformations and remains the leading cause of death. It has been estimated that in most cases the causes of heart defects remain unknown, while a growing number of studies have indicated the potential role of environmental agents as risk factors in CHD occurrence. In particular, maternal exposure to chemicals during the first trimester of pregnancy represents the most critical window of exposure for CHD. Specific classes of xenobiotics (e.g. organochlorine pesticides, organic solvents, air pollutants) have been identified as potential risk factors for CHD. Nonetheless, the knowledge gained is currently still incomplete as a consequence of the frequent heterogeneity of the methods applied and the difficulty in estimating the net effect of environmental pollution on the pregnant mother. The presence of multiple sources of pollution, both indoor and outdoor, together with individual lifestyle factors, may represent a further confounding element for association with the disease. A future new approach for research should probably focus on individual measurements of professional, domestic, and urban exposure to physical and chemical pollutants in order to accurately retrace the environmental exposure of parents of affected offspring during the pre-conceptional and pregnancy periods.

  8. Effects of environmental uncertainties on sonar detection performance prediction.

    PubMed

    Sha, Liewei; Nolte, Loren W

    2005-04-01

    The development of effective passive sonar systems depends upon the ability to accurately predict the performance of sonar detection algorithms in realistic ocean environments. Such environments are typically characterized by a high degree of uncertainty, thus limiting the usefulness of performance prediction approaches that assume a deterministic environment. Here we derive closed-form receiver operating characteristic (ROC) expressions for an optimal Bayesian detector and for several typical suboptimal detectors, based on a statistical model of environmental uncertainty. Various scenarios extended from an NRL benchmark shallow-water model were used to check the analytical ROC expressions and to illustrate the effect of environmental uncertainty on detection performance. The results showed that (1) optimal detection performance in an uncertain environment in diffuse noise depends primarily on the signal-to-noise ratio at the receivers and the rank of the signal matrix, where the rank is an effective representation of the scale of environmental uncertainty; (2) the ROC expression for the optimal Bayesian detector provides a more realistic performance upper bound than that obtained from conventional sonar equations that do not incorporate environmental uncertainty; and (3) detection performance predictions can be performed much faster than with commonly used numerical methods such as Monte Carlo performance evaluations.

  9. 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.

  10. 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

  11. 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.

  12. 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. PMID:26524122

  13. 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...

  14. 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

  15. Improved Prediction of CYP-Mediated Metabolism with Chemical Fingerprints.

    PubMed

    Zaretzki, Jed; Boehm, Kevin M; Swamidass, S Joshua

    2015-05-26

    Molecule and atom fingerprints, similar to path-based Daylight fingerprints, can substantially improve the accuracy of P450 site-of-metabolism prediction models. Only two chemical fingerprints have been used in metabolism prediction, so little is known about the importance of fingerprint parameters on site of metabolism predictions. It is possible that different fingerprints might yield more accurate models. Here, we study if tuning fingerprints to specific site of metabolism data sets can lead to improved models. We measure the impact of 484 specific chemical fingerprints on the accuracy of P450 site-of-metabolism prediction models on nine P450 isoform site of metabolism data sets. Using a range of search depths, we study path, circular, and subgraph fingerprints. Two different labelings, also, are considered, both standard SMILES labels and also a labeling that marks ring bonds differently than nonring bonds, enabling ortho, para, and meta positioning of substituents to be more clearly encoded. Optimal fingerprint models chosen by cross-validation performance on the full training data are, on average, 3.8% (Top-2; percent of molecules with a site of metabolism in the top two predictions) and 1.4% (AUC; area under the ROC curve) more accurate than base fingerprint models. These gains represent, respectively, a 25.6% and 16.7% reduction in error. A more rigorous assessment selects fingerprints within each cross-validation fold, sometimes selecting different fingerprints for different folds, but yielding a more reliable estimate of generalization error. In this assessment, averaging the scores from the top few fingerprints yields performances improvements of, on average, 3.0% (Top-2) and 0.7% (AUC). These gains are statistically significant and represent, respectively, a 20.1% and 8.8% reduction in error. Between different isoforms, not many consistencies were observed among the top performing fingerprints, with different fingerprints working best for different

  16. 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.

  17. 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

  18. Chemical and radiation environmental risk management: differences, commonalities, and challenges.

    PubMed

    Tran, N L; Locke, P A; Burke, T A

    2000-04-01

    Driven by differing statutory mandates and programmatic separation of regulatory responsibilities between federal, state, and tribal agencies, distinct chemical and radiation risk management strategies have evolved. In the field this separation poses real challenges since many of the major environmental risk management decisions we face today require the evaluation of both types of risks. Over the last decade, federal, state, and tribal agencies have continued to discuss their different approaches and explore areas where their activities could be harmonized. The current framework for managing public exposures to chemical carcinogens has been referred to as a "bottom up approach." Risk between 10(-4) and 10(-6) is established as an upper bound goal. In contrast, a "top down" approach that sets an upper bound dose limit and couples with site specific As Low As Reasonably Achievable Principle (ALARA), is in place to manage individual exposure to radiation. While radiation risk are typically managed on a cumulative basis, exposure to chemicals is generally managed on a chemical-by-chemical, medium-by-medium basis. There are also differences in the nature and size of sites where chemical and radiation contamination is found. Such differences result in divergent management concerns. In spite of these differences, there are several common and practical concerns among radiation and chemical risk managers. They include 1) the issue of cost for site redevelopment and long-term stewardship, 2) public acceptance and involvement, and 3) the need for flexible risk management framework to address the first two issues. This article attempts to synthesize key differences, opportunities for harmonization, and challenges ahead. PMID:10859777

  19. [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

  20. Discovery of characteristic molecular signatures for the simultaneous prediction and detection of environmental pollutants.

    PubMed

    Song, Mi-Kyung; Choi, Han-Seam; Park, Yong-Keun; Ryu, Jae-Chun

    2014-02-01

    Gene expression data may be very promising for the classification of toxicant types, but the development and application of transcriptomic-based gene classifiers for environmental toxicological applications are lacking compared to the biomedical sciences. Also, simultaneous classification across a set of toxicant types has not been investigated extensively. In the present study, we determined the transcriptomic response to three types of ubiquitous toxicants exposure in two types of human cell lines (HepG2 and HL-60), which are useful in vitro human model for evaluation of toxic substances that may affect human hepatotoxicity (e.g., polycyclic aromatic hydrocarbon [PAH] and persistent organic pollutant [POP]) and human leukemic myelopoietic proliferation (e.g., volatile organic compound [VOC]). The findings demonstrate characteristic molecular signatures that facilitated discrimination and prediction of the toxicant type. To evaluate changes in gene expression levels after exposure to environmental toxicants, we utilized 18 chemical substances; nine PAH toxicants, six VOC toxicants, and three POP toxicants. Unsupervised gene expression analysis resulted in a characteristic molecular signature for each toxicant group, and combination analysis of two separate multi-classifications indicated 265 genes as surrogate markers for predicting each group of toxicants with 100 % accuracy. Our results suggest that these expression signatures can be used as predictable and discernible surrogate markers for detection and prediction of environmental toxicant exposure. Furthermore, this approach could easily be extended to screening for other types of environmental toxicants. PMID:24197968

  1. 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

  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. PMID:26106136

  3. 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.

  4. 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.

  5. KCF-S: KEGG Chemical Function and Substructure for improved interpretability and prediction in chemical bioinformatics

    PubMed Central

    2013-01-01

    Background In order to develop hypothesis on unknown metabolic pathways, biochemists frequently rely on literature that uses a free-text format to describe functional groups or substructures. In computational chemistry or cheminformatics, molecules are typically represented by chemical descriptors, i.e., vectors that summarize information on its various properties. However, it is difficult to interpret these chemical descriptors since they are not directly linked to the terminology of functional groups or substructures that the biochemists use. Methods In this study, we used KEGG Chemical Function (KCF) format to computationally describe biochemical substructures in seven attributes that resemble biochemists' way of dealing with substructures. Results We established KCF-S (KCF-and-Substructures) format as an additional structural information of KCF. Applying KCF-S revealed the specific appearance of substructures from various datasets of molecules that describes the characteristics of the respective datasets. Structure-based clustering of molecules using KCF-S resulted the clusters in which molecular weights and structures were less diverse than those obtained by conventional chemical fingerprints. We further applied KCF-S to find the pairs of molecules that are possibly converted to each other in enzymatic reactions, and KCF-S clearly improved predictive performance than that presented previously. Conclusions KCF-S defines biochemical substructures with keeping interpretability, suggesting the potential to apply more studies on chemical bioinformatics. KCF and KCF-S can be automatically converted from Molfile format, enabling to deal with molecules from any data sources. PMID:24564846

  6. 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.

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

    PubMed

    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

    2015-11-01

    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.

  8. Predicting Arsenate Adsorption by Soils Using Soil Chemical Parameters in the Constant Capacitance Model

    NASA Astrophysics Data System (ADS)

    Goldberg, S. R.; Lesch, S. M.; Suarez, D. L.

    2004-12-01

    general regression model. This provided a completely independent evaluation of the ability of the constant capacitance model to describe As(V) adsorption. The model was able to accurately predict As(V) adsorption on three soils, qualitatively predict As(V) adsorption on one soil, and unable to prediction As(V) adsorption on one soil. Incorporation of these regression prediction equations into chemical speciation-transport models will allow simulation of soil solution As(V) concentrations under diverse environmental and agricultural management conditions without requiring soil specific adsorption data and subsequent parameter optimization.

  9. 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. PMID:27312897

  10. Environmental tobacco smoke: overview of chemical composition and genotoxic components.

    PubMed

    Löfroth, G

    1989-02-01

    Tobacco smoke contains numerous compounds emitted as gases and condensed tar particles. The sidestream smoke emissions, which constitute the major part of environmental tobacco smoke (ETS), are generally larger than the mainstream smoke emissions. Many of the organic compounds, belonging to a variety of chemical classes, are known to be genotoxic and carcinogenic. These include the known constituents, alkenes, nitrosamines, aromatic and heterocyclic hydrocarbons and amines. Emission of sidestream smoke in indoor environments with relatively low ventilation rates can result in pollutant concentrations above those generally encountered in ambient air in urban areas. The chemical characteristics of ETS thus support the indications that exposure to ETS can be causally associated with the induction of several types of cancer.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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. PMID

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. 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...

  5. Integrating chemical footprinting data into RNA secondary structure prediction.

    PubMed

    Zarringhalam, Kourosh; Meyer, Michelle M; Dotu, Ivan; Chuang, Jeffrey H; Clote, Peter

    2012-01-01

    Chemical and enzymatic footprinting experiments, such as shape (selective 2'-hydroxyl acylation analyzed by primer extension), yield important information about RNA secondary structure. Indeed, since the [Formula: see text]-hydroxyl is reactive at flexible (loop) regions, but unreactive at base-paired regions, shape yields quantitative data about which RNA nucleotides are base-paired. Recently, low error rates in secondary structure prediction have been reported for three RNAs of moderate size, by including base stacking pseudo-energy terms derived from shape data into the computation of minimum free energy secondary structure. Here, we describe a novel method, RNAsc (RNA soft constraints), which includes pseudo-energy terms for each nucleotide position, rather than only for base stacking positions. We prove that RNAsc is self-consistent, in the sense that the nucleotide-specific probabilities of being unpaired in the low energy Boltzmann ensemble always become more closely correlated with the input shape data after application of RNAsc. From this mathematical perspective, the secondary structure predicted by RNAsc should be 'correct', in as much as the shape data is 'correct'. We benchmark RNAsc against the previously mentioned method for eight RNAs, for which both shape data and native structures are known, to find the same accuracy in 7 out of 8 cases, and an improvement of 25% in one case. Furthermore, we present what appears to be the first direct comparison of shape data and in-line probing data, by comparing yeast asp-tRNA shape data from the literature with data from in-line probing experiments we have recently performed. With respect to several criteria, we find that shape data appear to be more robust than in-line probing data, at least in the case of asp-tRNA.

  6. pK(a) prediction from "Quantum Chemical Topology" descriptors.

    PubMed

    Harding, A P; Wedge, D C; Popelier, P L A

    2009-08-01

    Knowing the pK(a) of a compound gives insight into many properties relevant to many industries, in particular the pharmaceutical industry during drug development processes. In light of this, we have used the theory of Quantum Chemical Topology (QCT), to provide ab initio descriptors that are able to accurately predict pK(a) values for 228 carboxylic acids. This Quantum Topological Molecular Similarity (QTMS) study involved the comparison of 5 increasingly more expensive levels of theory to conclude that HF/6-31G(d) and B3LYP/6-311+G(2d,p) provided an accurate representation of the compounds studies. We created global and subset models for the carboxylic acids using Partial Least Square (PLS), Support Vector Machines (SVM), and Radial Basis Function Neural Networks (RBFNN). The models were extensively validated using 4-, 7-, and 10-fold cross-validation, with the validation sets selected based on systematic and random sampling. HF/6-31G(d) in conjunction with SVM provided the best statistics when taking into account the large increase in CPU time required to optimize the geometries at the B3LYP/6-311+G(2d,p) level. The SVM models provided an average q(2) value of 0.886 and an RMSE value of 0.293 for all the carboxylic acids, a q(2) of 0.825 and RMSE of 0.378 for the ortho-substituted acids, a q(2) of 0.923 and RMSE of 0.112 for the para- and meta-substituted acids, and a q(2) of 0.906 and RMSE of 0.268 for the aliphatic acids. Our method compares favorably to ACD/Laboratories, VCCLAB, SPARC, and ChemAxon's pK(a) prediction software based of the RMSE calculated by the leave-one-out method.

  7. 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.

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

    PubMed

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

    2016-05-01

    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 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

  9. 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

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

    PubMed

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

    2016-05-01

    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 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

  11. 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

  12. 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...

  13. 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.

  14. 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....

  15. 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

  16. 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)

  17. 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...

  18. 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...

  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. 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. PMID:24809491

  1. 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.

  2. Advances in mechanisms of activation and deactivation of environmental chemicals.

    PubMed Central

    Goldstein, J A; Faletto, M B

    1993-01-01

    Environmental chemicals are both activated and detoxified by phase I and phase II enzymes. The principal enzymes involved in phase I reactions are the cytochrome P-450s. The phase II enzymes include hydrolase and the conjugative enzymes such as glucuronyltransferases, glutathione transferases, N-acetyltransferase, and sulfotransferase. Although other phase I and phase II enzymes exist, the present review is limited to these enzymes. Once thought to be a single enzyme, multiple cytochrome P-450 enzymes have been purified and characterized from many different species across the evolutionary tree. The application of molecular biology techniques to this field has identified more than 150 cytochrome P-450 genes to date. At least 20-30 cytochrome P-450 enzymes appear to exist in each mammalian species, and many polymorphisms in these enzymes are being identified. The cytochrome P-450 enzymes can now be expressed in recombinant form using cDNA expression systems. The phase II conjugative enzymes add a hydrophilic moiety such as sulfate, glucuronide, or acetate to compounds, which increases their water solubility and facilitates their excretion. However, conjugates of a number of compounds also result in more reactive electrophilic species, which appear to be the ultimate carcinogens. Many of these phase II enzymes also represent families of enzymes, and polymorphisms can affect the ability of these enzymes to metabolize chemicals. Whenever possible, we have reviewed knowledge of the human enzymes involved in particular pathways. PMID:8354165

  3. Epigenetic effects of environmental chemicals bisphenol A and phthalates.

    PubMed

    Singh, Sher; Li, Steven Shoei-Lung

    2012-01-01

    The epigenetic effects on DNA methylation, histone modification, and expression of non-coding RNAs (including microRNAs) of environmental chemicals such as bisphenol A (BPA) and phthalates have expanded our understanding of the etiology of human complex diseases such as cancers and diabetes. Multiple lines of evidence from in vitro and in vivo models have established that epigenetic modifications caused by in utero exposure to environmental toxicants can induce alterations in gene expression that may persist throughout life. Epigenetics is an important mechanism in the ability of environmental chemicals to influence health and disease, and BPA and phthalates are epigenetically toxic. The epigenetic effect of BPA was clearly demonstrated in viable yellow mice by decreasing CpG methylation upstream of the Agouti gene, and the hypomethylating effect of BPA was prevented by maternal dietary supplementation with a methyl donor like folic acid or the phytoestrogen genistein. Histone H3 was found to be trimethylated at lysine 27 by BPA effect on EZH2 in a human breast cancer cell line and mice. BPA exposure of human placental cell lines has been shown to alter microRNA expression levels, and specifically, miR-146a was strongly induced by BPA treatment. In human breast cancer MCF7 cells, treatment with the phthalate BBP led to demethylation of estrogen receptor (ESR1) promoter-associated CpG islands, indicating that altered ESR1 mRNA expression by BBP is due to aberrant DNA methylation. Maternal exposure to phthalate DEHP was also shown to increase DNA methylation and expression levels of DNA methyltransferases in mouse testis. Further, some epigenetic effects of BPA and phthalates in female rats were found to be transgenerational. Finally, the available new technologies for global analysis of epigenetic alterations will provide insight into the extent and patterns of alterations between human normal and diseased tissues. In vitro models such as human embryonic stem cells

  4. 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.

  5. 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

  6. 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

  7. Expert-system comparison of structural determinants of chemical toxicity to environmental bacteria

    SciTech Connect

    Pangrekar, J.; Rosenkranz, H.S. . Dept. of Environmental and Occupational Health); Klopman, G. . Dept. of Chemistry)

    1994-06-01

    The CASE (computer automated structure evaluation) structure-activity relational expert system was used to analyze the toxicity of a database of chemical sets to environmental bacteria (aerobic heterotrophs, nitrosomonas, methanogens, and photobacteria [Microtox [reg sign]test]). The analyses revealed that the data sets related to each of the antimicrobial activities, albeit containing a relatively small number of chemicals, are characterized by structural determinants significantly associated with the probability of antimicrobial activity, as well as with antibacterial potency. Although there were a number of similarities among the structural determinants associated with each of these antimicrobial activities, there were also features unique to each assay that presumably reflect species-specific targets of bactericidal activity. Overall the assay for antimethanogenic activity appears to be the most informative as well as the one most predictive of the activity in the other three assays.

  8. 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).

  9. Environmental correction factors for predicting room sound pressure levels

    SciTech Connect

    Warnock, A.C.C.

    1998-10-01

    ARI Standard 885 provides a method for calculating sound pressure levels in room below plenums containing air-handling devices. An important step in the calculation is the correction of the sound power for the device from values provided by the manufacturer to values appropriate for use in occupied spaces. This correction is called the environmental adjustment factor. It compensates for the fact that sound power measured for a source placed outdoors or in a hemi-free field has been found to be greater at low frequencies than the sound power measured for the same source in a reverberation room. When making predictions of sound pressure level in a room using such sound power levels, one has to estimate the reduction in sound power caused by the room. Estimated reductions provided in ARI 885 were examined during ASHRAE research project RP-755 and found to be too large. Lower values are suggested in this paper.

  10. Environmental chemical exposures and risk of herpes zoster.

    PubMed Central

    Arndt, V; Vine, M F; Weigle, K

    1999-01-01

    This study investigated whether residence in Aberdeen, North Carolina, the location of the Aberdeen pesticides dumps site (a national priority list Superfund site containing organochlorine pesticides, volatile organic compounds, and metals), is associated with immune suppression as indicated by a higher incidence of herpes zoster and recent occurrences of other common infectious diseases. Study participants included 1,642 residents, 18-64 years of age, who responded to a telephone survey concerning potential occupational and recreational exposures to pesticides and other chemicals, lifetime history of herpes zoster (shingles), and the recent occurrence of other common infectious diseases. Stratified and logistic regression analyses were used to compare the cumulative incidence of herpes zoster among Aberdeen residents and residents of nearby communities. There was little evidence of an overall increased risk of herpes zoster among Aberdeen residents during the period 1951-1994 [relative risk (RR), 1.3; 95% confidence interval (CI), 0.8-2.1]. However, an elevated risk of herpes zoster was noted consistently among Aberdeen residents of younger ages as compared to residents of the nearby communities. The RR was 2.0 (CI, 1.0-4.0) among those 18-40 years of age and was not affected by controlling for potential confounders. The RR of herpes zoster was also consistently elevated in all age groups for the period before 1985. No differences were noted between residents of Aberdeen and those of the nearby communities with respect to the recent occurrence of other common infectious diseases. These results support the plausibility of an association between exposure to the Aberdeen pesticides dumps site and immune suppression and the potential use of herpes zoster as a marker of immune suppression in studies of environmental chemical exposures. Images Figure 1 PMID:10504152

  11. 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

  12. 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

  13. 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...

  14. Testing methods for developmental neurotoxicity of environmental chemicals.

    PubMed

    Claudio, L; Kwa, W C; Russell, A L; Wallinga, D

    2000-04-01

    Human brain development is slow and delicate, involving many unique, though interrelated, cellular events. The fetus and child are often more susceptible to chemical toxins that alter the structure and/or function of the brain, although susceptibility varies for individual neurotoxicants. Early exposure to neurotoxins has been implicated in neurological diseases and mental retardation. Pesticide exposures pose a particular concern since many are designed to be neurotoxic to pests and can also affect humans. Acknowledging the potential for vulnerability of the developing brain, EPA recently began to "call in" data on developmental neurotoxicity (DNT) from manufacturers of pesticides already registered and considered to be neurotoxic-around 140 pesticides. Chemicals are to be tested following the DNT testing guideline (OPPTS 870.6300). This paper assesses whether tests performed according to this guideline can effectively identify developmental neurotoxicants. We found the testing guideline deficient in several respects, including: It is not always triggered appropriately within the current tiered system for testing; It does not expose developing animals during all critical periods of vulnerability; It does not assess effects that may become evident later in life; It does not include methodology for consideration of pharmacokinetic variables; Methodology for assessment of neurobehavioral, neuropathological, and morphometry is highly variable; Testing of neurochemical changes is limited and not always required. We propose modifications to the EPA testing guideline that would improve its adequacy for assessing and predicting risks to infants and children. This paper emphasizes that deficiencies in the testing methodology for developmental neurotoxicants represent a significant gap and increase the uncertainty in the establishment of safe levels of exposure to developing individuals.

  15. 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...

  16. 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.

  17. 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

  18. Correlation of chemical shifts predicted by molecular dynamics simulations for partially disordered proteins

    PubMed Central

    Karp, Jerome M.; Erylimaz, Ertan

    2015-01-01

    There has been a longstanding interest in being able to accurately predict NMR chemical shifts from structural data. Recent studies have focused on using molecular dynamics (MD) simulation data as input for improved prediction. Here we examine the accuracy of chemical shift prediction for intein systems, which have regions of intrinsic disorder. We find that using MD simulation data as input for chemical shift prediction does not consistently improve prediction accuracy over use of a static X-ray crystal structure. This appears to result from the complex conformational ensemble of the disordered protein segments. We show that using accelerated molecular dynamics (aMD) simulations improves chemical shift prediction, suggesting that methods which better sample the conformational ensemble like aMD are more appropriate tools for use in chemical shift prediction for proteins with disordered regions. Moreover, our study suggests that data accurately reflecting protein dynamics must be used as input for chemical shift prediction in order to correctly predict chemical shifts in systems with disorder. PMID:25416617

  19. 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

  20. Variation in Chemical Defense Among Natural Populations of Common Toad, Bufo bufo, Tadpoles: the Role of Environmental Factors.

    PubMed

    Bókony, Veronika; Móricz, Ágnes M; Tóth, Zsófia; Gál, Zoltán; Kurali, Anikó; Mikó, Zsanett; Pásztor, Katalin; Szederkényi, Márk; Tóth, Zoltán; Ujszegi, János; Üveges, Bálint; Krüzselyi, Dániel; Capon, Robert J; Hoi, Herbert; Hettyey, Attila

    2016-04-01

    Defensive toxins are widespread in nature, yet we know little about how various environmental factors shape the evolution of chemical defense, especially in vertebrates. In this study we investigated the natural variation in the amount and composition of bufadienolide toxins, and the relative importance of ecological factors in predicting that variation, in larvae of the common toad, Bufo bufo, an amphibian that produces toxins de novo. We found that tadpoles' toxin content varied markedly among populations, and the number of compounds per tadpole also differed between two geographical regions. The most consistent predictor of toxicity was the strength of competition, indicating that tadpoles produced more compounds and larger amounts of toxins when coexisting with more competitors. Additionally, tadpoles tended to contain larger concentrations of bufadienolides in ponds that were less prone to desiccation, suggesting that the costs of toxin production can only be afforded by tadpoles that do not need to drastically speed up their development. Interestingly, this trade-off was not alleviated by higher food abundance, as periphyton biomass had negligible effect on chemical defense. Even more surprisingly, we found no evidence that higher predation risk enhances chemical defenses, suggesting that low predictability of predation risk and high mortality cost of low toxicity might select for constitutive expression of chemical defense irrespective of the actual level of predation risk. Our findings highlight that the variation in chemical defense may be influenced by environmental heterogeneity in both the need for, and constraints on, toxicity as predicted by optimal defense theory.

  1. Variation in Chemical Defense Among Natural Populations of Common Toad, Bufo bufo, Tadpoles: the Role of Environmental Factors.

    PubMed

    Bókony, Veronika; Móricz, Ágnes M; Tóth, Zsófia; Gál, Zoltán; Kurali, Anikó; Mikó, Zsanett; Pásztor, Katalin; Szederkényi, Márk; Tóth, Zoltán; Ujszegi, János; Üveges, Bálint; Krüzselyi, Dániel; Capon, Robert J; Hoi, Herbert; Hettyey, Attila

    2016-04-01

    Defensive toxins are widespread in nature, yet we know little about how various environmental factors shape the evolution of chemical defense, especially in vertebrates. In this study we investigated the natural variation in the amount and composition of bufadienolide toxins, and the relative importance of ecological factors in predicting that variation, in larvae of the common toad, Bufo bufo, an amphibian that produces toxins de novo. We found that tadpoles' toxin content varied markedly among populations, and the number of compounds per tadpole also differed between two geographical regions. The most consistent predictor of toxicity was the strength of competition, indicating that tadpoles produced more compounds and larger amounts of toxins when coexisting with more competitors. Additionally, tadpoles tended to contain larger concentrations of bufadienolides in ponds that were less prone to desiccation, suggesting that the costs of toxin production can only be afforded by tadpoles that do not need to drastically speed up their development. Interestingly, this trade-off was not alleviated by higher food abundance, as periphyton biomass had negligible effect on chemical defense. Even more surprisingly, we found no evidence that higher predation risk enhances chemical defenses, suggesting that low predictability of predation risk and high mortality cost of low toxicity might select for constitutive expression of chemical defense irrespective of the actual level of predation risk. Our findings highlight that the variation in chemical defense may be influenced by environmental heterogeneity in both the need for, and constraints on, toxicity as predicted by optimal defense theory. PMID:27059330

  2. Towards a systematic approach of effect prediction: A handbook as guide and aid for environmental prediction. A review

    NASA Astrophysics Data System (ADS)

    Jeltes, Robert; Hermens, Peter A. H.

    1990-03-01

    Environmental impact assessment (EIA) is based on the results of effect prediction. In general, there is much diversity in the expertise in the field of environmental prediction between the different categories of actors involved in EIA. In practice it became obvious in The Netherlands that the accessibility and comprehensibility of existing relevant information was insufficient. For improvement, a series of systematic handbooks on effect prediction, useful for all categories of actors, has been developed in The Netherlands. In this way, the selection of effect prediction methods to be used in concrete circumstances is improved and speeded up for all parties involved in environmental prediction. After a discussion of the purpose of the handbook, the realization and structure of the series are presented. Finally, the use and (potential) benefits of the handbooks for environmental management are indicated.

  3. Artificial streams in the assessment of environmental hazard of chemicals.

    PubMed

    Coffinet, S; Cossu-Leguille, C; Bassères, A; Gonnet, J-F; Vasseur, P

    2006-10-01

    Artificial streams are dynamic mesocosms, simulating aquatic systems and rivers. They are useful to study ecotoxicity of chemicals and their effects on flora and fauna colonizing the streams or introduced into the channels. These artificial rivers can also be used to study the influence of ecological and hydrodynamic parameters, such as the kind of substrate of river and flow rate. Responses of the bivalve Unio tumidus to substrate type (silt, sand, and pebbles) and water flow rate (high and low) were investigated after 15 and 35 days in the channels, in order to optimize the experimental conditions for ecotoxicity study with methyl methacrylate (MMA). The toxicological effects of different concentrations of MMA on bivalves and on communities of invertebrates and diatoms were determined after several weeks of exposure at a high flow rate. Biomarkers responses measured in the digestive gland and the gills of U. tumidus were the activities of detoxification systems as early indicators of toxicity and lipid peroxidation as a marker of cytotoxicity. Effects of MMA resulted in a decrease in antioxidant activities. Disturbances in bivalves appeared at lower concentrations than in communities. This indicates sensitivity of the biomarkers studied, which are predictive indicators of ecotoxicity.

  4. 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.

  5. Dynamical recurrent neural networks--towards environmental time series prediction.

    PubMed

    Aussem, A; Murtagh, F; Sarazin, M

    1995-06-01

    Dynamical Recurrent Neural Networks (DRNN) (Aussem 1995a) are a class of fully recurrent networks obtained by modeling synapses as autoregressive filters. By virtue of their internal dynamic, these networks approximate the underlying law governing the time series by a system of nonlinear difference equations of internal variables. They therefore provide history-sensitive forecasts without having to be explicitly fed with external memory. The model is trained by a local and recursive error propagation algorithm called temporal-recurrent-backpropagation. The efficiency of the procedure benefits from the exponential decay of the gradient terms backpropagated through the adjoint network. We assess the predictive ability of the DRNN model with meterological and astronomical time series recorded around the candidate observation sites for the future VLT telescope. The hope is that reliable environmental forecasts provided with the model will allow the modern telescopes to be preset, a few hours in advance, in the most suited instrumental mode. In this perspective, the model is first appraised on precipitation measurements with traditional nonlinear AR and ARMA techniques using feedforward networks. Then we tackle a complex problem, namely the prediction of astronomical seeing, known to be a very erratic time series. A fuzzy coding approach is used to reduce the complexity of the underlying laws governing the seeing. Then, a fuzzy correspondence analysis is carried out to explore the internal relationships in the data. Based on a carefully selected set of meteorological variables at the same time-point, a nonlinear multiple regression, termed nowcasting (Murtagh et al. 1993, 1995), is carried out on the fuzzily coded seeing records. The DRNN is shown to outperform the fuzzy k-nearest neighbors method. PMID:7496587

  6. Dynamical recurrent neural networks--towards environmental time series prediction.

    PubMed

    Aussem, A; Murtagh, F; Sarazin, M

    1995-06-01

    Dynamical Recurrent Neural Networks (DRNN) (Aussem 1995a) are a class of fully recurrent networks obtained by modeling synapses as autoregressive filters. By virtue of their internal dynamic, these networks approximate the underlying law governing the time series by a system of nonlinear difference equations of internal variables. They therefore provide history-sensitive forecasts without having to be explicitly fed with external memory. The model is trained by a local and recursive error propagation algorithm called temporal-recurrent-backpropagation. The efficiency of the procedure benefits from the exponential decay of the gradient terms backpropagated through the adjoint network. We assess the predictive ability of the DRNN model with meterological and astronomical time series recorded around the candidate observation sites for the future VLT telescope. The hope is that reliable environmental forecasts provided with the model will allow the modern telescopes to be preset, a few hours in advance, in the most suited instrumental mode. In this perspective, the model is first appraised on precipitation measurements with traditional nonlinear AR and ARMA techniques using feedforward networks. Then we tackle a complex problem, namely the prediction of astronomical seeing, known to be a very erratic time series. A fuzzy coding approach is used to reduce the complexity of the underlying laws governing the seeing. Then, a fuzzy correspondence analysis is carried out to explore the internal relationships in the data. Based on a carefully selected set of meteorological variables at the same time-point, a nonlinear multiple regression, termed nowcasting (Murtagh et al. 1993, 1995), is carried out on the fuzzily coded seeing records. The DRNN is shown to outperform the fuzzy k-nearest neighbors method.

  7. Human AP Endonuclease 1: A Potential Marker for the Prediction of Environmental Carcinogenesis Risk

    PubMed Central

    Park, Jae Sung; Kim, Hye Lim; Kim, Yeo Jin; Weon, Jong-Il; Sung, Mi-Kyung; Chung, Hai Won; Seo, Young Rok

    2014-01-01

    Human apurinic/apyrimidinic endonuclease 1 (APE1) functions mainly in DNA repair as an enzyme removing AP sites and in redox signaling as a coactivator of various transcription factors. Based on these multifunctions of APE1 within cells, numerous studies have reported that the alteration of APE1 could be a crucial factor in development of human diseases such as cancer and neurodegeneration. In fact, the study on the combination of an individual's genetic make-up with environmental factors (gene-environment interaction) is of great importance to understand the development of diseases, especially lethal diseases including cancer. Recent reports have suggested that the human carcinogenic risk following exposure to environmental toxicants is affected by APE1 alterations in terms of gene-environment interactions. In this review, we initially outline the critical APE1 functions in the various intracellular mechanisms including DNA repair and redox regulation and its roles in human diseases. Several findings demonstrate that the change in expression and activity as well as genetic variability of APE1 caused by environmental chemical (e.g., heavy metals and cigarette smoke) and physical carcinogens (ultraviolet and ionizing radiation) is likely associated with various cancers. These enable us to ultimately suggest APE1 as a vital marker for the prediction of environmental carcinogenesis risk. PMID:25243052

  8. 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

    2014-10-01

    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.

  9. 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

    2014-10-01

    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

  10. Predicting environmental risk: A road map for the future.

    PubMed

    Jager, Tjalling

    2016-01-01

    Frameworks for environmental risk assessment (ERA) focus on comparing results from separate exposure and effect assessments. Exposure assessment generally relies on mechanistic fate models, whereas the effects assessment is anchored in standard test protocols and descriptive statistics. This discrepancy prevents a useful link between these two pillars of ERA, and jeopardizes the realism and efficacy of the entire process. Similar to exposure assessment, effects assessment requires a mechanistic approach to translate the output of fate models into predictions for impacts on populations and food webs. The aim of this study was to discuss (1) the central importance of the individual level, (2) different strategies of dealing with biological complexity, and (3) the role that toxicokinetic-toxicodynamic (TKTD) models, energy budgets, and molecular biology play in a mechanistic revision of the ERA framework. Consequently, an outline for a risk assessment paradigm was developed that incorporates a mechanistic effects assessment in a consistent manner, and a "roadmap for the future." Such a roadmap may play a critical role to eventually arrive at a more scientific and efficient ERA process, and needs to be used to shape our long-term research agendas. PMID:27484139

  11. 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...

  12. 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 ...

  13. 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

  14. 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.

  15. Molecular Modeling to Predict and Understand Chemical Toxicity

    EPA Science Inventory

    The risk posed to human health and the environment by chemicals that result from human activity often must be evaluated when relevant elements of the preferred data set are unavailable. Therefore, strategies are needed that estimate this information and prioritize the outstanding...

  16. 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...

  17. 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.

  18. Prenatal Exposures to Environmental Chemicals and Children's Neurodevelopment: An Update

    PubMed Central

    2013-01-01

    This review surveys the recent literature on the neurodevelopmental impacts of chemical exposures during pregnancy. The review focuses primarily on chemicals of recent concern, including phthalates, bisphenol-A, polybrominated diphenyl ethers, and perfluorinated compounds, but also addresses chemicals with longer histories of investigation, including air pollutants, lead, methylmercury, manganese, arsenic, and organophosphate pesticides. For some chemicals of more recent concern, the available literature does not yet afford strong conclusions about neurodevelopment toxicity. In such cases, points of disagreement among studies are identified and suggestions provided for approaches to resolution of the inconsistencies, including greater standardization of methods for expressing exposure and assessing outcomes. PMID:23515885

  19. 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.

  20. 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.

  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. 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 ...

  3. 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...

  4. 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…

  5. 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...

  6. Predicted thermochemistry for chemical conversions of 5-hydroxymethylfurfural

    NASA Astrophysics Data System (ADS)

    Assary, Rajeev S.; Redfern, Paul C.; Hammond, Jeff R.; Greeley, Jeffrey; Curtiss, Larry A.

    2010-09-01

    The thermochemistry of various chemical transformations of 5-hydroxy methyl furfural (HMF) were investigated using highly accurate G AUSSIAN-4 (G4) theory. The conversion of HMF to nonane through aldol condensation, hydrogenation, and hydrogenolysis reactions was found to be thermodynamically favorable. The hydrogenation reactions involving the keto groups in the nonane reaction sequence were found to be enhanced at low temperatures and high pressures of H 2. The hydrogenation, selective oxidation, and hydration of HMF were also found to be thermodynamically favorable. Gas phase enthalpies of formation of all the intermediate compounds were calculated at the G4 level of theory and compared against existing experimental data.

  7. Predicted thermochemistry for chemical conversions of 5-hydroxymethylfurfural.

    SciTech Connect

    Assary, R. S.; Redfern, P. C.; Hammond, J. R.; Greeley, J.; Curtiss, L. A.; Northwestern Univ.

    2010-09-10

    The thermochemistry of various chemical transformations of 5-hydroxy methyl furfural (HMF) were investigated using highly accurate Gaussian-4 (G4) theory. The conversion of HMF to nonane through aldol condensation, hydrogenation, and hydrogenolysis reactions was found to be thermodynamically favorable. The hydrogenation reactions involving the keto groups in the nonane reaction sequence were found to be enhanced at low temperatures and high pressures of H{sub 2}. The hydrogenation, selective oxidation, and hydration of HMF were also found to be thermodynamically favorable. Gas phase enthalpies of formation of all the intermediate compounds were calculated at the G4 level of theory and compared against existing experimental data.

  8. 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.

  9. 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.

  10. 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. PMID:24284198

  11. PREDICTION OF CHEMICAL RESIDUES IN AQUATIC ORGANISMS FOR A FIELD DISCHARGE SITUATION.

    EPA Science Inventory

    A field study was performed which compared predicted and measured concentrations of chemicals in receiving water organisms from three sampling locations on Five Mile Creek, Birmingham, Al. Two point source discharges, both from coke manufacturing facilities, were included in the ...

  12. Prediction of Chemical Vapor Deposition Rates on Monofilaments and Its Implications for Fiber Properties

    NASA Technical Reports Server (NTRS)

    Gokoglu, S. A.; Kuczmarski, M.; Veitch, L. C.

    1992-01-01

    Deposition rates are predicted in a cylindrical upflow reactor designed for chemical vapor deposition (CVD) on monofilaments. Deposition of silicon from silane in a hydrogen carrier gas is chosen as a relevant example. The effects of gas and surface chemistry are studied in a two-dimensional axisymmetric flow field for this chemically well-studied system. Model predictions are compared to experimental CVD rate measurements. The differences in some physical and chemical phenomena between such small diameter (about 150 microns) fiber substrates and other typical CVD substrates are highlighted. The influence of the Soret mass transport mechanism is determined to be extraordinarily significant. The difficulties associated with the accurate measurement and control of the fiber temperature are discussed. Model prediction sensitivities are investigated with respect to fiber temperatures, fiber radii, Soret transport, and chemical kinetic parameters. The implications of the predicted instantaneous rates are discussed relative to the desired fiber properties for both the batch and the continuous processes.

  13. EPA's Toxcast ™ Program for Predicting Hazard and Priortizing Toxicity Testing of Environemntal Chemicals (T)

    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 ...

  14. Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling

    SciTech Connect

    Valerio, Luis G. . E-mail: luis.valerio@FDA.HHS.gov; Arvidson, Kirk B.; Chanderbhan, Ronald F.; Contrera, Joseph F.

    2007-07-01

    Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool of current interest is MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a group of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogenic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals

  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. 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.

  17. 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

  18. The CONCEPTS Global Ice-Ocean Prediction System: Establishing an Environmental Prediction Capability in Canada

    NASA Astrophysics Data System (ADS)

    Pellerin, Pierre; Smith, Gregory; Testut, Charles-Emmanuel; Surcel Colan, Dorina; Roy, Francois; Reszka, Mateusz; Dupont, Frederic; Lemieux, Jean-Francois; Beaudoin, Christiane; He, Zhongjie; Belanger, Jean-Marc; Deacu, Daniel; Lu, Yimin; Buehner, Mark; Davidson, Fraser; Ritchie, Harold; Lu, Youyu; Drevillon, Marie; Tranchant, Benoit; Garric, Gilles

    2015-04-01

    Here we describe a new system implemented recently at the Canadian Meteorological Centre (CMC) entitled the Global Ice Ocean Prediction System (GIOPS). GIOPS provides ice and ocean analyses and 10 day forecasts daily at 00GMT on a global 1/4° resolution grid. GIOPS includes a full multivariate ocean data assimilation system that combines satellite observations of sea level anomaly and sea surface temperature (SST) together with in situ observations of temperature and salinity. In situ observations are obtained from a variety of sources including: the Argo network of autonomous profiling floats, moorings, ships of opportunity, marine mammals and research cruises. Ocean analyses are blended with sea ice analyses produced by the Global Ice Analysis System.. GIOPS has been developed as part of the Canadian Operational Network of Coupled Environmental PredicTion Systems (CONCEPTS) tri-departmental initiative between Environment Canada, Fisheries and Oceans Canada and National Defense. The development of GIOPS was made through a partnership with Mercator-Océan, a French operational oceanography group. Mercator-Océan provided the ocean data assimilation code and assistance with the system implementation. GIOPS has undergone a rigorous evaluation of the analysis, trial and forecast fields demonstrating its capacity to provide high-quality products in a robust and reliable framework. In particular, SST and ice concentration forecasts demonstrate a clear benefit with respect to persistence. These results support the use of GIOPS products within other CMC operational systems, and more generally, as part of a Government of Canada marine core service. Impact of a two-way coupling between the GEM atmospheric model and NEMO-CICE ocean-ice model will also be presented.

  19. Significance of vapor phase chemical reactions on CVD rates predicted by chemically frozen and local thermochemical equilibrium boundary layer theories

    NASA Technical Reports Server (NTRS)

    Gokoglu, Suleyman A.

    1988-01-01

    This paper investigates the role played by vapor-phase chemical reactions on CVD rates by comparing the results of two extreme theories developed to predict CVD mass transport rates in the absence of interfacial kinetic barrier: one based on chemically frozen boundary layer and the other based on local thermochemical equilibrium. Both theories consider laminar convective-diffusion boundary layers at high Reynolds numbers and include thermal (Soret) diffusion and variable property effects. As an example, Na2SO4 deposition was studied. It was found that gas phase reactions have no important role on Na2SO4 deposition rates and on the predictions of the theories. The implications of the predictions of the two theories to other CVD systems are discussed.

  20. CURRENT STATE OF PREDICTING THE RESPIRATORY ALLERGY POTENTIAL OF CHEMICALS: WHAT ARE THE ISSUES?

    EPA Science Inventory

    Current State of Predicting the Respiratory Allergy Potential of Chemicals: What Are the Issues? M I. Gilmour1 and S. E. Loveless2, 1USEPA, Research Triangle Park, NC and 2DuPont Haskell Laboratory, Newark, DE.

    Many chemicals are clearly capable of eliciting immune respon...

  1. Students' Predictions about the Sensory Properties of Chemical Compounds: Additive versus Emergent Frameworks

    ERIC Educational Resources Information Center

    Talanquer, Vicente

    2008-01-01

    We investigated general chemistry students' intuitive ideas about the expected properties of the products of a chemical reaction. In particular, we analyzed college chemistry students' predictions about the color, smell, and taste of the products of chemical reactions represented at the molecular level. The study was designed to explore the extent…

  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

    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...

  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. 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...

  6. [Application of near infrared reflectance spectroscopy to predict meat chemical compositions: a review].

    PubMed

    Tao, Lin-Li; Yang, Xiu-Juan; Deng, Jun-Ming; Zhang, Xi

    2013-11-01

    In contrast to conventional methods for the determination of meat chemical composition, near infrared reflectance spectroscopy enables rapid, simple, secure and simultaneous assessment of numerous meat properties. The present review focuses on the use of near infrared reflectance spectroscopy to predict meat chemical compositions. The potential of near infrared reflectance spectroscopy to predict crude protein, intramuscular fat, fatty acid, moisture, ash, myoglobin and collagen of beef, pork, chicken and lamb is reviewed. This paper discusses existing questions and reasons in the current research. According to the published results, although published results vary considerably, they suggest that near-infrared reflectance spectroscopy shows a great potential to replace the expensive and time-consuming chemical analysis of meat composition. In particular, under commercial conditions where simultaneous measurements of different chemical components are required, near infrared reflectance spectroscopy is expected to be the method of choice. The majority of studies selected feature-related wavelengths using principal components regression, developed the calibration model using partial least squares and modified partial least squares, and estimated the prediction accuracy by means of cross-validation using the same sample set previously used for the calibration. Meat fatty acid composition predicted by near-infrared spectroscopy and non-destructive prediction and visualization of chemical composition in meat using near-infrared hyperspectral imaging and multivariate regression are the hot studying field now. On the other hand, near infrared reflectance spectroscopy shows great difference for predicting different attributes of meat quality which are closely related to the selection of calibration sample set, preprocessing of near-infrared spectroscopy and modeling approach. Sample preparation also has an important effect on the reliability of NIR prediction; in particular

  7. 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

  8. 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.

  9. 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 ...

  10. 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.

  11. 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.

  12. High pressure electrides: a predictive chemical and physical theory.

    PubMed

    Miao, Mao-Sheng; Hoffmann, Roald

    2014-04-15

    Electrides, in which electrons occupy interstitial regions in the crystal and behave as anions, appear as new phases for many elements (and compounds) under high pressure. We propose a unified theory of high pressure electrides (HPEs) by treating electrons in the interstitial sites as filling the quantized orbitals of the interstitial space enclosed by the surrounding atom cores, generating what we call an interstitial quasi-atom, ISQ. With increasing pressure, the energies of the valence orbitals of atoms increase more significantly than the ISQ levels, due to repulsion, exclusion by the atom cores, effectively giving the valence electrons less room in which to move. At a high enough pressure, which depends on the element and its orbitals, the frontier atomic electron may become higher in energy than the ISQ, resulting in electron transfer to the interstitial space and the formation of an HPE. By using a He lattice model to compress (with minimal orbital interaction at moderate pressures between the surrounding He and the contained atoms or molecules) atoms and an interstitial space, we are able to semiquantitatively explain and predict the propensity of various elements to form HPEs. The slopes in energy of various orbitals with pressure (s > p > d) are essential for identifying trends across the entire Periodic Table. We predict that the elements forming HPEs under 500 GPa will be Li, Na (both already known to do so), Al, and, near the high end of this pressure range, Mg, Si, Tl, In, and Pb. Ferromagnetic electrides for the heavier alkali metals, suggested by Pickard and Needs, potentially compete with transformation to d-group metals. PMID:24702165

  13. Predicting carcinogenicity of diverse chemicals using probabilistic neural network modeling approaches

    SciTech Connect

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

    2013-10-15

    Robust global models capable of discriminating positive and non-positive carcinogens; and predicting carcinogenic potency of chemicals in rodents were developed. The dataset of 834 structurally diverse chemicals extracted from Carcinogenic Potency Database (CPDB) was used which contained 466 positive and 368 non-positive carcinogens. Twelve non-quantum mechanical molecular descriptors were derived. Structural diversity of the chemicals and nonlinearity in the data were evaluated using Tanimoto similarity index and Brock–Dechert–Scheinkman statistics. Probabilistic neural network (PNN) and generalized regression neural network (GRNN) models were constructed for classification and function optimization problems using the carcinogenicity end point in rat. Validation of the models was performed using the internal and external procedures employing a wide series of statistical checks. PNN constructed using five descriptors rendered classification accuracy of 92.09% in complete rat data. The PNN model rendered classification accuracies of 91.77%, 80.70% and 92.08% in mouse, hamster and pesticide data, respectively. The GRNN constructed with nine descriptors yielded correlation coefficient of 0.896 between the measured and predicted carcinogenic potency with mean squared error (MSE) of 0.44 in complete rat data. The rat carcinogenicity model (GRNN) applied to the mouse and hamster data yielded correlation coefficient and MSE of 0.758, 0.71 and 0.760, 0.46, respectively. The results suggest for wide applicability of the inter-species models in predicting carcinogenic potency of chemicals. Both the PNN and GRNN (inter-species) models constructed here can be useful tools in predicting the carcinogenicity of new chemicals for regulatory purposes. - Graphical abstract: Figure (a) shows classification accuracies (positive and non-positive carcinogens) in rat, mouse, hamster, and pesticide data yielded by optimal PNN model. Figure (b) shows generalization and predictive

  14. 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.

  15. 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...

  16. 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...

  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. Quantitative Regression Models for the Prediction of Chemical Properties by an Efficient Workflow.

    PubMed

    Yin, Yongmin; Xu, Congying; Gu, Shikai; Li, Weihua; Liu, Guixia; Tang, Yun

    2015-10-01

    Rapid safety assessment is more and more needed for the increasing chemicals both in chemical industries and regulators around the world. The traditional experimental methods couldn't meet the current demand any more. With the development of the information technology and the growth of experimental data, in silico modeling has become a practical and rapid alternative for the assessment of chemical properties, especially for the toxicity prediction of organic chemicals. In this study, a quantitative regression workflow was built by KNIME to predict chemical properties. With this regression workflow, quantitative values of chemical properties can be obtained, which is different from the binary-classification model or multi-classification models that can only give qualitative results. To illustrate the usage of the workflow, two predictive models were constructed based on datasets of Tetrahymena pyriformis toxicity and Aqueous solubility. The qcv (2) and qtest (2) of 5-fold cross validation and external validation for both types of models were greater than 0.7, which implies that our models are robust and reliable, and the workflow is very convenient and efficient in prediction of various chemical properties. PMID:27490968

  20. 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. PMID:14753679

  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. 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.

  3. Predicting (17)O NMR chemical shifts of polyoxometalates using density functional theory.

    PubMed

    Sharma, Rupali; Zhang, Jie; Ohlin, C André

    2016-03-21

    We have investigated the computation of (17)O NMR chemical shifts of a wide range of polyoxometalates using density functional theory. The effects of basis sets and exchange-correlation functionals are explored, and whereas pure DFT functionals generally predict the chemical shifts of terminal oxygen sites quite well, hybrid functionals are required for the prediction of accurate chemical shifts in conjunction with linear regression. By using PBE0/def2-tzvp//PBE0/cc-pvtz(H-Ar), lanl2dz(K-) we have computed the chemical shifts of 37 polyoxometalates, corresponding to 209 (17)O NMR signals. We also show that at this level of theory the protonation-induced pH dependence of the chemical shift of the triprotic hexaniobate Lindqvist anion, [HxNb6O19]((8-x)), can be reproduced, which suggests that hypotheses regarding loci of protonation can be confidently tested. PMID:26925832

  4. 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...

  5. 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.

  6. 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,...

  7. 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...

  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. QSAR prediction of estrogen activity for a large set of diverse chemicals under the guidance of OECD principles.

    PubMed

    Liu, Huanxiang; Papa, Ester; Gramatica, Paola

    2006-11-01

    A large number of environmental chemicals, known as endocrine-disrupting chemicals, are suspected of disrupting endocrine functions by mimicking or antagonizing natural hormones, and such chemicals may pose a serious threat to the health of humans and wildlife. They are thought to act through a variety of mechanisms, mainly estrogen-receptor-mediated mechanisms of toxicity. However, it is practically impossible to perform thorough toxicological tests on all potential xenoestrogens, and thus, the quantitative structure--activity relationship (QSAR) provides a promising method for the estimation of a compound's estrogenic activity. Here, QSAR models of the estrogen receptor binding affinity of a large data set of heterogeneous chemicals have been built using theoretical molecular descriptors, giving full consideration to the new OECD principles in regulation for QSAR acceptability, during model construction and assessment. An unambiguous multiple linear regression (MLR) algorithm was used to build the models, and model predictive ability was validated by both internal and external validation. The applicability domain was checked by the leverage approach to verify prediction reliability. The results obtained using several validation paths indicate that the proposed QSAR model is robust and satisfactory, and can provide a feasible and practical tool for the rapid screening of the estrogen activity of organic compounds.

  10. Prediction of the rodent carcinogenicity of organic compounds from their chemical structures using the FALS method.

    PubMed Central

    Moriguchi, I; Hirano, H; Hirono, S

    1996-01-01

    Fuzzy adaptive least-squares (FALS), a pattern recognition method recently developed in our laboratory for correlating structure with activity rating, was used to generate quantitative structure-activity relationship (QSAR) models on the carcinogenicity of organic compounds of several chemical classes. Using the predictive models obtained from the chemical class-based FALS QSAR approach, the rodent carcinogenicity or noncarcinogenicity of a group of organic chemicals currently being tested by the U.S. National Toxicology Program was estimated from their chemical structures. PMID:8933054

  11. Prediction of the rodent carcinogenicity of organic compounds from their chemical structures using the FALS method

    SciTech Connect

    Moriguchi, Ikuo; Hirono, Shuichi; Hirano, Hiroyuki

    1996-10-01

    Fuzzy adaptive least-squares (FALS), a pattern recognition method recently developed in our laboratory for correlating structure with activity rating, was used to generate quantitative structure-activity relationship (QSAR) models on the carcinogenicity of organic compounds of several chemical classes. Using the predictive models obtained from the chemical class-based FALS QSAR approach, the rodent carcinogenicity or noncarcinogenicity of a group of organic chemicals currently being tested by the U.S. National Toxicology Program was estimated from their chemical structures. 12 refs., 4 tabs.

  12. 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...

  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. 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...

  14. 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. PMID:26613357

  15. 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.

  16. 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

  17. 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

  18. 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...

  19. 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...

  20. 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.

  1. 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...

  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. 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...

  4. Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts.

    PubMed Central

    Hong, Huixiao; Tong, Weida; Fang, Hong; Shi, Leming; Xie, Qian; Wu, Jie; Perkins, Roger; Walker, John D; Branham, William; Sheehan, Daniel M

    2002-01-01

    A number of environmental chemicals, by mimicking natural hormones, can disrupt endocrine function in experimental animals, wildlife, and humans. These chemicals, called "endocrine-disrupting chemicals" (EDCs), are such a scientific and public concern that screening and testing 58,000 chemicals for EDC activities is now statutorily mandated. Computational chemistry tools are important to biologists because they identify chemicals most important for in vitro and in vivo studies. Here we used a computational approach with integration of two rejection filters, a tree-based model, and three structural alerts to predict and prioritize estrogen receptor (ER) ligands. The models were developed using data for 232 structurally diverse chemicals (training set) with a 10(6) range of relative binding affinities (RBAs); we then validated the models by predicting ER RBAs for 463 chemicals that had ER activity data (testing set). The integrated model gave a lower false negative rate than any single component for both training and testing sets. When the integrated model was applied to approximately 58,000 potential EDCs, 80% (approximately 46,000 chemicals) were predicted to have negligible potential (log RBA < -4.5, with log RBA = 2.0 for estradiol) to bind ER. The ability to process large numbers of chemicals to predict inactivity for ER binding and to categorically prioritize the remainder provides one biologic measure to prioritize chemicals for entry into more expensive assays (most chemicals have no biologic data of any kind). The general approach for predicting ER binding reported here may be applied to other receptors and/or reversible binding mechanisms involved in endocrine disruption. PMID:11781162

  5. 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…

  6. Computational prediction of microRNA networks incorporating environmental toxicity and disease etiology

    NASA Astrophysics Data System (ADS)

    Li, Jie; Wu, Zengrui; Cheng, Feixiong; Li, Weihua; Liu, Guixia; Tang, Yun

    2014-07-01

    MicroRNAs (miRNAs) play important roles in multiple biological processes and have attracted much scientific attention recently. Their expression can be altered by environmental factors (EFs), which are associated with many diseases. Identification of the phenotype-genotype relationships among miRNAs, EFs, and diseases at the network level will help us to better understand toxicology mechanisms and disease etiologies. In this study, we developed a computational systems toxicology framework to predict new associations among EFs, miRNAs and diseases by integrating EF structure similarity and disease phenotypic similarity. Specifically, three comprehensive bipartite networks: EF-miRNA, EF-disease and miRNA-disease associations, were constructed to build predictive models. The areas under the receiver operating characteristic curves using 10-fold cross validation ranged from 0.686 to 0.910. Furthermore, we successfully inferred novel EF-miRNA-disease networks in two case studies for breast cancer and cigarette smoke. Collectively, our methods provide a reliable and useful tool for the study of chemical risk assessment and disease etiology involving miRNAs.

  7. 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.

  8. Toxic effects of occupational and environmental chemicals on the testes

    SciTech Connect

    Sever, L.E.; Hessol, N.A.

    1983-01-01

    This paper examines evidence for effects of occupational chemicals on male reproduction. We consider primarily human data, and much of that from epidemiologic studies. We use animal studies to illustrate points, but the theme is the human experience. The approach is based on examining reproductive function as an indicator of toxic effects. Testicular structure and function is briefly discussed. We provide a brief review of relevant structure, function and hormonal control. We describe the anatomy of the testis and its histological structure. We then discuss the testis from the point of view of exocrine and endocrine function and the relationship of the testis to other endocrinological organs. This is followed by a review of methods for assessing human testicular function, including reproductive histories, sperm analysis, assessment of hormonal status, and histological studies. Although the primary focus is on human studies, we consider briefly general categories of chemicals shown to have a testicular effect in animal studies and also animal evidence of mechanisms of action associated with testicular toxicology. Specific chemicals shown to affect reproduction in the human male are reviewed and directions for future research in this area discussed.

  9. 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...

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

    PubMed Central

    Judson, Richard S.; Houck, Keith A.; Kavlock, Robert J.; Knudsen, Thomas B.; Martin, Matthew T.; Mortensen, Holly M.; Reif, David M.; Rotroff, Daniel M.; Shah, Imran; Richard, Ann M.; Dix, David J.

    2010-01-01

    Background 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 screening and prioritizing chemicals for potential human toxicity using in vitro assays and in silico approaches. Objectives This project aims to evaluate the use of in vitro assays for understanding the types of molecular and pathway perturbations caused by environmental chemicals and to build initial prioritization models of in vivo toxicity. Methods We tested 309 mostly pesticide active chemicals in 467 assays across nine technologies, including high-throughput cell-free assays and cell-based assays, in multiple human primary cells and cell lines plus rat primary hepatocytes. Both individual and composite scores for effects on genes and pathways were analyzed. Results Chemicals displayed a broad spectrum of activity at the molecular and pathway levels. We saw many expected interactions, including endocrine and xenobiotic metabolism enzyme activity. Chemicals ranged in promiscuity across pathways, from no activity to affecting dozens of pathways. We found a statistically significant inverse association between the number of pathways perturbed by a chemical at low in vitro concentrations and the lowest in vivo dose at which a chemical causes toxicity. We also found associations between a small set of in vitro assays and rodent liver lesion formation. Conclusions This approach promises to provide meaningful data on the thousands of untested environmental chemicals and to guide targeted testing of environmental contaminants. PMID:20368123

  12. 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

  13. 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. PMID:25341502

  14. Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression.

    PubMed

    Nahta, Rita; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Andrade-Vieira, Rafaela; Bay, Sarah N; Brown, Dustin G; 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; Ryan, Elizabeth P; Salem, Hosni K; Scovassi, A Ivana; Singh, Neetu; Vaccari, Monica; Vento, Renza; Vondráček, Jan; Wade, Mark; Woodrick, Jordan; Bisson, William H

    2015-06-01

    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.

  15. 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.

  16. 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

  17. 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

  18. Role of Environmental Chemical Insult in Neuronal Cell Death and Cytoskeleton Damage.

    PubMed

    Aung, Kyaw Htet; Tsukahara, Shinji; Maekawa, Fumihiko; Nohara, Keiko; Nakamura, Kazuaki; Tanoue, Akito

    2015-01-01

    Environmental influences, such as chemical exposure, have long been considered potential risk factors for neurodegenerative disorders, including neuromuscular diseases. However, no definitive links between environmental chemical exposure and a pathogenic mechanism of neurodegenerative disease has yet been established. In this study, we describe that exposure to arsenic, an environmental pollutant naturally found in drinking water, induces neuronal cell death and alteration of morphology, particularly neurite outgrowth and in the cytoskeleton of neurons. Since progressive cell loss accompanied by the alteration of neuronal structures and cytoskeleton is considered the major pathologic feature of neurodegenerative disorders, arsenic-induced neurotoxicity might contribute to an etiologic mechanism of some neurodegenerative diseases. Further, we discuss the importance of in vitro assay, particularly an embryonic toxicity test, for assessing the neurotoxicity of chemicals, because most of chemicals found in our environment remain to be evaluated regarding their neurotoxicity risk for neurodegenerative diseases.

  19. 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. PMID:27118737

  20. Role of Environmental Chemical Insult in Neuronal Cell Death and Cytoskeleton Damage.

    PubMed

    Aung, Kyaw Htet; Tsukahara, Shinji; Maekawa, Fumihiko; Nohara, Keiko; Nakamura, Kazuaki; Tanoue, Akito

    2015-01-01

    Environmental influences, such as chemical exposure, have long been considered potential risk factors for neurodegenerative disorders, including neuromuscular diseases. However, no definitive links between environmental chemical exposure and a pathogenic mechanism of neurodegenerative disease has yet been established. In this study, we describe that exposure to arsenic, an environmental pollutant naturally found in drinking water, induces neuronal cell death and alteration of morphology, particularly neurite outgrowth and in the cytoskeleton of neurons. Since progressive cell loss accompanied by the alteration of neuronal structures and cytoskeleton is considered the major pathologic feature of neurodegenerative disorders, arsenic-induced neurotoxicity might contribute to an etiologic mechanism of some neurodegenerative diseases. Further, we discuss the importance of in vitro assay, particularly an embryonic toxicity test, for assessing the neurotoxicity of chemicals, because most of chemicals found in our environment remain to be evaluated regarding their neurotoxicity risk for neurodegenerative diseases. PMID:26235574

  1. Prediction of Drug Indications Based on Chemical Interactions and Chemical Similarities

    PubMed Central

    Huang, Guohua; Lu, Yin; Lu, Changhong; Cai, Yu-Dong

    2015-01-01

    Discovering potential indications of novel or approved drugs is a key step in drug development. Previous computational approaches could be categorized into disease-centric and drug-centric based on the starting point of the issues or small-scaled application and large-scale application according to the diversity of the datasets. Here, a classifier has been constructed to predict the indications of a drug based on the assumption that interactive/associated drugs or drugs with similar structures are more likely to target the same diseases using a large drug indication dataset. To examine the classifier, it was conducted on a dataset with 1,573 drugs retrieved from Comprehensive Medicinal Chemistry database for five times, evaluated by 5-fold cross-validation, yielding five 1st order prediction accuracies that were all approximately 51.48%. Meanwhile, the model yielded an accuracy rate of 50.00% for the 1st order prediction by independent test on a dataset with 32 other drugs in which drug repositioning has been confirmed. Interestingly, some clinically repurposed drug indications that were not included in the datasets are successfully identified by our method. These results suggest that our method may become a useful tool to associate novel molecules with new indications or alternative indications with existing drugs. PMID:25821813

  2. 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.

  3. 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. PMID:27222376

  4. 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...

  5. Mapping Proteome-Wide Targets of Environmental Chemicals Using Reactivity-Based Chemoproteomic Platforms.

    PubMed

    Medina-Cleghorn, Daniel; Bateman, Leslie A; Ford, Breanna; Heslin, Ann; Fisher, Karl J; Dalvie, Esha D; Nomura, Daniel K

    2015-10-22

    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.

  6. In Silico Prediction of Chemically Induced Mutagenicity: How to Use QSAR Models and Interpret Their Results.

    PubMed

    Mombelli, Enrico; Raitano, Giuseppa; Benfenati, Emilio

    2016-01-01

    Information on genotoxicity is an essential piece of information gathering for a comprehensive toxicological characterization of chemicals. Several QSAR models that can predict Ames genotoxicity are freely available for download from the Internet and they can provide relevant information for the toxicological profiling of chemicals. Indeed, they can be straightforwardly used for predicting the presence or absence of genotoxic hazards associated with the interactions of chemicals with DNA.Nevertheless, and despite the ease of use of these models, the scientific challenge is to assess the reliability of information that can be obtained from these tools. This chapter provides instructions on how to use freely available QSAR models and on how to interpret their predictions.

  7. In Silico Prediction of Chemically Induced Mutagenicity: How to Use QSAR Models and Interpret Their Results.

    PubMed

    Mombelli, Enrico; Raitano, Giuseppa; Benfenati, Emilio

    2016-01-01

    Information on genotoxicity is an essential piece of information gathering for a comprehensive toxicological characterization of chemicals. Several QSAR models that can predict Ames genotoxicity are freely available for download from the Internet and they can provide relevant information for the toxicological profiling of chemicals. Indeed, they can be straightforwardly used for predicting the presence or absence of genotoxic hazards associated with the interactions of chemicals with DNA.Nevertheless, and despite the ease of use of these models, the scientific challenge is to assess the reliability of information that can be obtained from these tools. This chapter provides instructions on how to use freely available QSAR models and on how to interpret their predictions. PMID:27311463

  8. TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts.

    PubMed

    Shen, Yang; Delaglio, Frank; Cornilescu, Gabriel; Bax, Ad

    2009-08-01

    NMR chemical shifts in proteins depend strongly on local structure. The program TALOS establishes an empirical relation between 13C, 15N and 1H chemical shifts and backbone torsion angles phi and psi (Cornilescu et al. J Biomol NMR 13 289-302, 1999). Extension of the original 20-protein database to 200 proteins increased the fraction of residues for which backbone angles could be predicted from 65 to 74%, while reducing the error rate from 3 to 2.5%. Addition of a two-layer neural network filter to the database fragment selection process forms the basis for a new program, TALOS+, which further enhances the prediction rate to 88.5%, without increasing the error rate. Excluding the 2.5% of residues for which TALOS+ makes predictions that strongly differ from those observed in the crystalline state, the accuracy of predicted phi and psi angles, equals +/-13 degrees . Large discrepancies between predictions and crystal structures are primarily limited to loop regions, and for the few cases where multiple X-ray structures are available such residues are often found in different states in the different structures. The TALOS+ output includes predictions for individual residues with missing chemical shifts, and the neural network component of the program also predicts secondary structure with good accuracy.

  9. CADASTER QSPR Models for Predictions of Melting and Boiling Points of Perfluorinated Chemicals.

    PubMed

    Bhhatarai, Barun; Teetz, Wolfram; Liu, Tao; Öberg, Tomas; Jeliazkova, Nina; Kochev, Nikolay; Pukalov, Ognyan; Tetko, Igor V; Kovarich, Simona; Papa, Ester; Gramatica, Paola

    2011-03-14

    Quantitative structure property relationship (QSPR) studies on per- and polyfluorinated chemicals (PFCs) on melting point (MP) and boiling point (BP) are presented. The training and prediction chemicals used for developing and validating the models were selected from Syracuse PhysProp database and literatures. The available experimental data sets were split in two different ways: a) random selection on response value, and b) structural similarity verified by self-organizing-map (SOM), in order to propose reliable predictive models, developed only on the training sets and externally verified on the prediction sets. Individual linear and non-linear approaches based models developed by different CADASTER partners on 0D-2D Dragon descriptors, E-state descriptors and fragment based descriptors as well as consensus model and their predictions are presented. In addition, the predictive performance of the developed models was verified on a blind external validation set (EV-set) prepared using PERFORCE database on 15 MP and 25 BP data respectively. This database contains only long chain perfluoro-alkylated chemicals, particularly monitored by regulatory agencies like US-EPA and EU-REACH. QSPR models with internal and external validation on two different external prediction/validation sets and study of applicability-domain highlighting the robustness and high accuracy of the models are discussed. Finally, MPs for additional 303 PFCs and BPs for 271 PFCs were predicted for which experimental measurements are unknown.

  10. An environmental chamber for investigating the evaporation of volatile chemicals.

    PubMed

    Dillon, H K; Rumph, P F

    1998-03-01

    An inexpensive test chamber has been constructed that provides an environment appropriate for testing the effects of temperature and chemical interactions on gaseous emissions from test solutions. Temperature, relative humidity, and ventilation rate can be controlled and a well-mixed atmosphere can be maintained. The system is relatively simple and relies on heated tap water or ice to adjust the temperature. Temperatures ranging from 9 to 21 degrees C have been maintained. At an average temperature of 15.1 degrees C, temperatures at any location within the chamber vary by no more than 0.5 degree C, and the temperature of the test solution within the chamber varies by no more than 0.1 degree C. The temperatures within the chamber are stable enough to generate precise steady-state concentrations. The wind velocities within the chamber are reproducible from run to run. Consequently, the effect of velocity on the rate of evaporation of a test chemical is expected to be uniform from run to run. Steady-state concentrations can be attained in less than 1 hour at an air exchange rate of about 5 per hour. PMID:9530806

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

    PubMed

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

    2014-05-19

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

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

    PubMed

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

    2014-05-19

    The research aims to develop multispecies quantitative structure-activity relationships (QSARs) modeling tools capable of predicting the acute toxicity of diverse chemicals in various Organization for Economic Co-operation and Development (OECD) recommended test species of different trophic levels for regulatory toxicology. Accordingly, the ensemble learning (EL) approach based classification and regression QSAR models, such as decision treeboost (DTB) and decision tree forest (DTF) implementing stochastic gradient boosting and bagging algorithms were developed using the algae (P. subcapitata) experimental toxicity data for chemicals. The EL-QSAR models were successfully applied to predict toxicities of wide groups of chemicals in other test species including algae (S. obliguue), daphnia, fish, and bacteria. Structural diversity of the selected chemicals and those of the end-point toxicity data of five different test species were tested using the Tanimoto similarity index and Kruskal-Wallis (K-W) statistics. Predictive and generalization abilities of the constructed QSAR models were compared using statistical parameters. The developed QSAR models (DTB and DTF) yielded a considerably high classification accuracy in complete data of model building (algae) species (97.82%, 99.01%) and ranged between 92.50%-94.26% and 92.14%-94.12% in four test species, respectively, whereas regression QSAR models (DTB and DTF) rendered high correlation (R(2)) between the measured and model predicted toxicity end-point values and low mean-squared error in model building (algae) species (0.918, 0.15; 0.905, 0.21) and ranged between 0.575 and 0.672, 0.18-0.51 and 0.605-0.689 and 0.20-0.45 in four different test species. The developed QSAR models exhibited good predictive and generalization abilities in different test species of varied trophic levels and can be used for predicting the toxicities of new chemicals for screening and prioritization of chemicals for regulation. PMID:24738471

  13. Drug-target interaction prediction from chemical, genomic and pharmacological data in an integrated framework

    PubMed Central

    Yamanishi, Yoshihiro; Kotera, Masaaki; Kanehisa, Minoru; Goto, Susumu

    2010-01-01

    Motivation: In silico prediction of drug–target interactions from heterogeneous biological data is critical in the search for drugs and therapeutic targets for known diseases such as cancers. There is therefore a strong incentive to develop new methods capable of detecting these potential drug–target interactions efficiently. Results: In this article, we investigate the relationship between the chemical space, the pharmacological space and the topology of drug–target interaction networks, and show that drug–target interactions are more correlated with pharmacological effect similarity than with chemical structure similarity. We then develop a new method to predict unknown drug–target interactions from chemical, genomic and pharmacological data on a large scale. The proposed method consists of two steps: (i) prediction of pharmacological effects from chemical structures of given compounds and (ii) inference of unknown drug–target interactions based on the pharmacological effect similarity in the framework of supervised bipartite graph inference. The originality of the proposed method lies in the prediction of potential pharmacological similarity for any drug candidate compounds and in the integration of chemical, genomic and pharmacological data in a unified framework. In the results, we make predictions for four classes of important drug–target interactions involving enzymes, ion channels, GPCRs and nuclear receptors. Our comprehensively predicted drug–target interaction networks enable us to suggest many potential drug–target interactions and to increase research productivity toward genomic drug discovery. Supplementary information: Datasets and all prediction results are available at http://cbio.ensmp.fr/~yyamanishi/pharmaco/. Availability: Softwares are available upon request. Contact: yoshihiro.yamanishi@ensmp.fr PMID:20529913

  14. 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

  15. Development of computer program ENMASK for prediction of residual environmental masking-noise spectra, from any three independent environmental parameters

    SciTech Connect

    Chang, Y.-S.; Liebich, R. E.; Chun, K. C.

    2000-03-31

    Residual environmental sound can mask intrusive4 (unwanted) sound. It is a factor that can affect noise impacts and must be considered both in noise-impact studies and in noise-mitigation designs. Models for quantitative prediction of sensation level (audibility) and psychological effects of intrusive noise require an input with 1/3 octave-band spectral resolution of environmental masking noise. However, the majority of published residual environmental masking-noise data are given with either octave-band frequency resolution or only single A-weighted decibel values. A model has been developed that enables estimation of 1/3 octave-band residual environmental masking-noise spectra and relates certain environmental parameters to A-weighted sound level. This model provides a correlation among three environmental conditions: measured residual A-weighted sound-pressure level, proximity to a major roadway, and population density. Cited field-study data were used to compute the most probable 1/3 octave-band sound-pressure spectrum corresponding to any selected one of these three inputs. In turn, such spectra can be used as an input to models for prediction of noise impacts. This paper discusses specific algorithms included in the newly developed computer program ENMASK. In addition, the relative audibility of the environmental masking-noise spectra at different A-weighted sound levels is discussed, which is determined by using the methodology of program ENAUDIBL.

  16. 3D Chemical Similarity Networks for Structure-Based Target Prediction and Scaffold Hopping.

    PubMed

    Lo, Yu-Chen; Senese, Silvia; Damoiseaux, Robert; Torres, Jorge Z

    2016-08-19

    Target identification remains a major challenge for modern drug discovery programs aimed at understanding the molecular mechanisms of drugs. Computational target prediction approaches like 2D chemical similarity searches have been widely used but are limited to structures sharing high chemical similarity. Here, we present a new computational approach called chemical similarity network analysis pull-down 3D (CSNAP3D) that combines 3D chemical similarity metrics and network algorithms for structure-based drug target profiling, ligand deorphanization, and automated identification of scaffold hopping compounds. In conjunction with 2D chemical similarity fingerprints, CSNAP3D achieved a >95% success rate in correctly predicting the drug targets of 206 known drugs. Significant improvement in target prediction was observed for HIV reverse transcriptase (HIVRT) compounds, which consist of diverse scaffold hopping compounds targeting the nucleotidyltransferase binding site. CSNAP3D was further applied to a set of antimitotic compounds identified in a cell-based chemical screen and identified novel small molecules that share a pharmacophore with Taxol and display a Taxol-like mechanism of action, which were validated experimentally using in vitro microtubule polymerization assays and cell-based assays.

  17. 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)

  18. High-Throughput Dietary Exposure Predictions for Chemical Migrants from Food Packaging Materials

    EPA Science Inventory

    United States Environmental Protection Agency researchers have developed a Stochastic Human Exposure and Dose Simulation High -Throughput (SHEDS-HT) model for use in prioritization of chemicals under the ExpoCast program. In this research, new methods were implemented in SHEDS-HT...

  19. Prediction of biodegradability from chemical structure: Modeling or ready biodegradation test data

    SciTech Connect

    Loonen, H.; Lindgren, F.; Hansen, B.

    1999-08-01

    Biodegradation data were collected and evaluated for 894 substances with widely varying chemical structures. All data were determined according to the Japanese Ministry of International Trade and Industry (MITI) I test protocol. The MITI I test is a screening test for ready biodegradability and has been described by Organization for Economic Cooperation and Development (OECD) test guideline 301 C and European Union (EU) test guideline C4F. The chemicals were characterized by a set of 127 predefined structural fragments. This data set was used to develop a model for the prediction of the biodegradability of chemicals under standardized OECD and EU ready biodegradation test conditions. Partial least squares (PLS) discriminant analysis was used for the model development. The model was evaluated by means of internal cross-validation and repeated external validation. The importance of various structural fragments and fragment interactions was investigated. The most important fragments include the presence of a long alkyl chain; hydroxy, ester, and acid groups (enhancing biodegradation); and the presence of one or more aromatic rings and halogen substituents (regarding biodegradation). More than 85% of the model predictions were correct for using the complete data set. The not readily biodegradable predictions were slightly better than the readily biodegradable predictions (86 vs 84%). The average percentage of correct predictions from four external validation studies was 83%. Model optimization by including fragment interactions improve the model predicting capabilities to 89%. It can be concluded that the PLS model provides predictions of high reliability for a diverse range of chemical structures. The predictions conform to the concept of readily biodegradable (or not readily biodegradable) as defined by OECD and EU test guidelines.

  20. 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.

    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. 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.

  1. Prediction of developmental chemical toxicity based on gene networks of human embryonic stem cells.

    PubMed

    Yamane, Junko; Aburatani, Sachiyo; Imanishi, Satoshi; Akanuma, Hiromi; Nagano, Reiko; Kato, Tsuyoshi; Sone, Hideko; Ohsako, Seiichiroh; Fujibuchi, Wataru

    2016-07-01

    Predictive toxicology using stem cells or their derived tissues has gained increasing importance in biomedical and pharmaceutical research. Here, we show that toxicity category prediction by support vector machines (SVMs), which uses qRT-PCR data from 20 categorized chemicals based on a human embryonic stem cell (hESC) system, is improved by the adoption of gene networks, in which network edge weights are added as feature vectors when noisy qRT-PCR data fail to make accurate predictions. The accuracies of our system were 97.5-100% for three toxicity categories: neurotoxins (NTs), genotoxic carcinogens (GCs) and non-genotoxic carcinogens (NGCs). For two uncategorized chemicals, bisphenol-A and permethrin, our system yielded reasonable results: bisphenol-A was categorized as an NGC, and permethrin was categorized as an NT; both predictions were supported by recently published papers. Our study has two important features: (i) as the first study to employ gene networks without using conventional quantitative structure-activity relationships (QSARs) as input data for SVMs to analyze toxicogenomics data in an hESC validation system, it uses additional information of gene-to-gene interactions to significantly increase prediction accuracies for noisy gene expression data; and (ii) using only undifferentiated hESCs, our study has considerable potential to predict late-onset chemical toxicities, including abnormalities that occur during embryonic development. PMID:27207879

  2. Prediction of developmental chemical toxicity based on gene networks of human embryonic stem cells

    PubMed Central

    Yamane, Junko; Aburatani, Sachiyo; Imanishi, Satoshi; Akanuma, Hiromi; Nagano, Reiko; Kato, Tsuyoshi; Sone, Hideko; Ohsako, Seiichiroh; Fujibuchi, Wataru

    2016-01-01

    Predictive toxicology using stem cells or their derived tissues has gained increasing importance in biomedical and pharmaceutical research. Here, we show that toxicity category prediction by support vector machines (SVMs), which uses qRT-PCR data from 20 categorized chemicals based on a human embryonic stem cell (hESC) system, is improved by the adoption of gene networks, in which network edge weights are added as feature vectors when noisy qRT-PCR data fail to make accurate predictions. The accuracies of our system were 97.5–100% for three toxicity categories: neurotoxins (NTs), genotoxic carcinogens (GCs) and non-genotoxic carcinogens (NGCs). For two uncategorized chemicals, bisphenol-A and permethrin, our system yielded reasonable results: bisphenol-A was categorized as an NGC, and permethrin was categorized as an NT; both predictions were supported by recently published papers. Our study has two important features: (i) as the first study to employ gene networks without using conventional quantitative structure-activity relationships (QSARs) as input data for SVMs to analyze toxicogenomics data in an hESC validation system, it uses additional information of gene-to-gene interactions to significantly increase prediction accuracies for noisy gene expression data; and (ii) using only undifferentiated hESCs, our study has considerable potential to predict late-onset chemical toxicities, including abnormalities that occur during embryonic development. PMID:27207879

  3. Can Exposure to Environmental Chemicals Increase the Risk of Diabetes Type 1 Development?

    PubMed Central

    Stene, Lars Christian

    2015-01-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune disease, where destruction of beta-cells causes insulin deficiency. The incidence of T1DM has increased in the last decades and cannot entirely be explained by genetic predisposition. Several environmental factors are suggested to promote T1DM, like early childhood enteroviral infections and nutritional factors, but the evidence is inconclusive. Prenatal and early life exposure to environmental pollutants like phthalates, bisphenol A, perfluorinated compounds, PCBs, dioxins, toxicants, and air pollutants can have negative effects on the developing immune system, resulting in asthma-like symptoms and increased susceptibility to childhood infections. In this review the associations between environmental chemical exposure and T1DM development is summarized. Although information on environmental chemicals as possible triggers for T1DM is sparse, we conclude that it is plausible that environmental chemicals can contribute to T1DM development via impaired pancreatic beta-cell and immune-cell functions and immunomodulation. Several environmental factors and chemicals could act together to trigger T1DM development in genetically susceptible individuals, possibly via hormonal or epigenetic alterations. Further observational T1DM cohort studies and animal exposure experiments are encouraged. PMID:25883945

  4. Environmental chemicals relevant for respiratory hypersensitivity: the indoor environment.

    PubMed

    Becher, R; Hongslo, J K; Jantunen, M J; Dybing, E

    1996-08-01

    The allergenic constituents of non-industrial indoor environments are predominantly found in the biologic fraction. Several reports have related biological particles such as mites and their excreta, dander from pets and other furred animals, fungi and bacteria to allergic manifestations including respiratory hypersensitivity among the occupants of buildings. Also, bacterial cell-wall components and the spores of toxin-producing moulds may contribute to the induction of hypersensitivity, but the relevance for human health is not yet determined. The knowledge regarding hypersensitivity and asthmatic reactions after exposure to chemical agents is primarily based on data from occupational settings with much higher exposure levels than usually found in non-industrial indoor environments. However, there is evidence that indoor exposure to tobacco smoke, some volatile organic compounds (VOC) and various combustion products (either by using unvented stoves or from outdoor sources) can be related to asthmatic symptoms. In some susceptible individuals, the development of respiratory hypersensitivity or elicitation of asthmatic symptoms may also be related to the indiscriminate use of different household products followed by exposure to compounds such as diisocyanates, organic acid anhydrides, formaldehyde, styrene and hydroquinone. At present, the contribution of the indoor environment both to the development of respiratory hypersensitivity and for triggering asthmatic symptoms is far from elucidated.

  5. Increased medication use in a community environmentally exposed to chemicals.

    PubMed

    Bowler, Rosemarie M; Gysens, Sabine; Hartney, Christopher; Ngo, Long; Rauch, Stephen S; Midtling, John

    2002-10-01

    An epidemiological health study compared the health status of residents of a town exposed to an accidental Catacarb chemical release from an adjacent oil refinery, with the health status of demographically similar residents of an unexposed town in the region. Few studies of Catacarb's effects on humans exist; however, animal studies have shown it to be a respiratory, gastro-intestinal, dermatological and visual irritant. As part of the study, health questionnaires assessing pre- and post exposure symptoms, illnesses and medication use were mailed to residents in both towns. Medication use is sometimes reported to be a more objective and reliable measure of health outcomes. The current paper compared medication use of exposed and unexposed residents. Significant increases after exposure were found in the use of the following medications: antacid, asthma medication, cough and cold medication, eye medication, headache medication and sleep medication. These increases were consistent with reported symptoms, albeit of greater magnitude; no increase in medication use for other illnesses was reported. Medication use in this sample was consistent with patients' report of symptoms and may be a better measure of outcome. PMID:12502236

  6. Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

    SciTech Connect

    Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Tropsha, Alexander

    2015-04-15

    Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. - Highlights: • It was compiled the largest publicly-available skin sensitization dataset. • Predictive QSAR models were developed for skin sensitization. • Developed models have higher prediction accuracy than OECD QSAR Toolbox. • Putative

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

    SciTech Connect

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

    1987-01-01

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

  8. Linking empirical estimates of body burden of environmental chemicals and wellness using NHANES data.

    PubMed

    Gennings, Chris; Ellis, Rhonda; Ritter, Joseph K

    2012-02-01

    Biomonitoring of industrial chemicals in human tissues and fluids has shown that all people carry a "body burden" of synthetic chemicals. Although measurement of an environmental chemical in a person's tissues/fluids is an indication of exposure, it does not necessarily mean the exposure concentration is sufficient to cause an adverse effect. Since humans are exposed to multiple chemicals, there may be a combination effect (e.g., additive, synergistic) associated with low-level exposures to multiple classes of contaminants, which may impact a variety of organ systems. The objective of this research is to link measures of body burden of environmental chemicals and a "holistic" measure of wellness. The approach is demonstrated using biomonitoring data from the National Health and Nutrition Examination Surveys (NHANES). Forty-two chemicals were selected for analysis based on their detection levels. Six biological pathway-specific indices were evaluated using groups of chemicals associated with each pathway. Five of the six pathways were negatively associated with wellness. Three non-zero interaction terms were detected which may provide empirical evidence of crosstalk across pathways. The approach identified five of the 42 chemicals from a variety of classes (metals, pesticides, furans, polycyclic aromatic hydrocarbons) as accounting for 71% of the weight linking body burden to wellness. Significant interactions were detected indicating the effect of smoking is exacerbated by body burden of environmental chemicals. Use of a holistic index on both sides of the exposure-health equation is a novel and promising empirical "systems biology" approach to risk evaluation of complex environmental exposures.

  9. Linking Empirical Estimates of Body Burden of Environmental Chemicals and Wellness using NHANES Data

    PubMed Central

    Gennings, Chris; Ellis, Rhonda; Ritter, Joe

    2011-01-01

    Biomonitoring of industrial chemicals in human tissues and fluids has shown that all people carry a “body burden” of synthetic chemicals. Although measurement of an environmental chemical in a person’s tissues/fluids is an indication of exposure, it does not necessarily mean the exposure concentration is sufficient to cause an adverse effect. Since humans are exposed to multiple chemicals, there may be a combination effect (e.g., additive, synergistic) associated with low-level exposures to multiple classes of contaminants, which may impact a variety of organ systems. The objective of this research is to link measures of body burden of environmental chemicals and a “holistic” measure of wellness. The approach is demonstrated using biomonitoring data from the National Health and Nutrition Examination Surveys (NHANES). Forty-two chemicals were selected for analysis based on their detection levels. Six biological pathway-specific indices were evaluated using groups of chemicals associated with each pathway. Five of the six pathways were negatively associated with wellness. Three non-zero interaction terms were detected which may provide empirical evidence of crosstalk across pathways. The approach identified five of the 42 chemicals from a variety of classes (metals, pesticides, furans, polycyclic aromatic hydrocarbons) as accounting for 71% of the weight linking body burden to wellness. Significant interactions were detected indicating the effect of smoking is exacerbated by body burden of environmental chemicals. Use of a holistic index on both sides of the exposure-health equation is a novel and promising empirical “systems biology” approach to risk evaluation of complex environmental exposures. PMID:22208743

  10. Using Neural Networks for 13C NMR Chemical Shift Prediction-Comparison with Traditional Methods

    NASA Astrophysics Data System (ADS)

    Meiler, Jens; Maier, Walter; Will, Martin; Meusinger, Reinhard

    2002-08-01

    Interpretation of 13C chemical shifts is essential for structure elucidation of organic molecules by NMR. In this article, we present an improved neural network approach and compare its performance to that of commonly used approaches. Specifically, our recently proposed neural network ( J. Chem. Inf. Comput. Sci. 2000, 40, 1169-1176) is improved by introducing an extended hybrid numerical description of the carbon atom environment, resulting in a standard deviation (std. dev.) of 2.4 ppm for an independent test data set of ˜42,500 carbons. Thus, this neural network allows fast and accurate 13C NMR chemical shift prediction without the necessity of access to molecule or fragment databases. For an unbiased test dataset containing 100 organic structures the accuracy of the improved neural network was compared to that of a prediction method based on the HOSE code ( hierarchically ordered spherical description of environment) using S PECI NFO. The results show the neural network predictions to be of quality (std. dev.=2.7 ppm) comparable to that of the HOSE code prediction (std. dev.=2.6 ppm). Further we compare the neural network predictions to those of a wide variety of other 13C chemical shift prediction tools including incremental methods (C HEMD RAW, S PECT OOL), quantum chemical calculation (G AUSSIAN, C OSMOS), and HOSE code fragment-based prediction (S PECI NFO, ACD/CNMR, P REDICTI T NMR) for the 47 13C-NMR shifts of Taxol, a natural product including many structural features of organic substances. The smallest standard deviations were achieved here with the neural network (1.3 ppm) and S PECI NFO (1.0 ppm).

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

    PubMed

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

    2013-09-01

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

  12. A hybrid method for prediction and repositioning of drug Anatomical Therapeutic Chemical classes.

    PubMed

    Chen, Lei; Lu, Jing; Zhang, Ning; Huang, Tao; Cai, Yu-Dong

    2014-04-01

    In the Anatomical Therapeutic Chemical (ATC) classification system, therapeutic drugs are divided into 14 main classes according to the organ or system on which they act and their chemical, pharmacological and therapeutic properties. This system, recommended by the World Health Organization (WHO), provides a global standard for classifying medical substances and serves as a tool for international drug utilization research to improve quality of drug use. In view of this, it is necessary to develop effective computational prediction methods to identify the ATC-class of a given drug, which thereby could facilitate further analysis of this system. In this study, we initiated an attempt to develop a prediction method and to gain insights from it by utilizing ontology information of drug compounds. Since only about one-fourth of drugs in the ATC classification system have ontology information, a hybrid prediction method combining the ontology information, chemical interaction information and chemical structure information of drug compounds was proposed for the prediction of drug ATC-classes. As a result, by using the Jackknife test, the 1st prediction accuracies for identifying the 14 main ATC-classes in the training dataset, the internal validation dataset and the external validation dataset were 75.90%, 75.70% and 66.36%, respectively. Analysis of some samples with false-positive predictions in the internal and external validation datasets indicated that some of them may even have a relationship with the false-positive predicted ATC-class, suggesting novel uses of these drugs. It was conceivable that the proposed method could be used as an efficient tool to identify ATC-classes of novel drugs or to discover novel uses of known drugs.

  13. Chemical Engineering of Enzymes: Altered Catalytic Activity, Predictable Selectivity and Exceptional Stability of the Semisynthetic Peroxidase Seleno-Subtilisin

    NASA Astrophysics Data System (ADS)

    Häring, Dietmar; Schreier, Peter

    The increasing demand for enzymes as highly selective, mild, and environmentally benign catalysts is often limited by the lack of an enzyme with the desired catalytic activity or substrate selectivity and by their instability in biotechnological processes. The previous answers to these problems comprised genetically engineered enzymes and several classes of enzyme mimics. Here we describe the potential of chemical enzyme engineering: native enzymes can be modified by merely chemical means and basic equipment yielding so-called semisynthetic enzymes. Thus, the high substrate selectivity of the enzymatic peptide framework is combined with the catalytic versatility of a synthetic active site. We illustrate the potential of chemically engineered enzymes with the conception of the semisynthetic peroxidase seleno-subtilisin. First, the serine endoprotease subtilisin was crystallized and cross-linked with glutaraldehyde to give cross-linked enzyme crystals which were found to be insoluble in water or organic solvents and highly stable. Second, serine 221 in the active site (Enz-OH) was chemically converted into an oxidized derivative of selenocystein (Enz-SeO2H). As a consequence, the former proteolytic enzyme gained peroxidase activity and catalyzed the selective reduction of hydroperoxides. Due to the identical binding sites of the semisynthetic peroxidase and the protease, the substrate selectivity of seleno-subtilisin was predictable in view of the well-known selectivity of subtilisin.

  14. EFFECTS OF USING THE CB05 VERSUS THE CB4 CHEMICAL MECHANISMS ON MODEL PREDICTIONS

    EPA Science Inventory

    The Carbon Bond 4 (CB4) chemical mechanism has been widely used for many years in box and air quality models to predict the effect of atmospheric chemistry on pollutant concentrations. Because of the importance of this mechanism and the length of time since its original developm...

  15. EFFECTS OF USING THE CB05 VERSUS THE CB4 CHEMICAL MECHANISM ON MODEL PREDICTIONS

    EPA Science Inventory

    The Carbon Bond 4 (CB4) chemical mechanism has been widely used for many years in box and air quality models to predict the effect of atmospheric chemistry on pollutant concentrations. Because of the importance of this mechanism and the length of time since its original developm...

  16. Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure

    PubMed Central

    Mathews, David H.; Disney, Matthew D.; Childs, Jessica L.; Schroeder, Susan J.; Zuker, Michael; Turner, Douglas H.

    2004-01-01

    A dynamic programming algorithm for prediction of RNA secondary structure has been revised to accommodate folding constraints determined by chemical modification and to include free energy increments for coaxial stacking of helices when they are either adjacent or separated by a single mismatch. Furthermore, free energy parameters are revised to account for recent experimental results for terminal mismatches and hairpin, bulge, internal, and multibranch loops. To demonstrate the applicability of this method, in vivo modification was performed on 5S rRNA in both Escherichia coli and Candida albicans with 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho-p-toluene sulfonate, dimethyl sulfate, and kethoxal. The percentage of known base pairs in the predicted structure increased from 26.3% to 86.8% for the E. coli sequence by using modification constraints. For C. albicans, the accuracy remained 87.5% both with and without modification data. On average, for these sequences and a set of 14 sequences with known secondary structure and chemical modification data taken from the literature, accuracy improves from 67% to 76%. This enhancement primarily reflects improvement for three sequences that are predicted with <40% accuracy on the basis of energetics alone. For these sequences, inclusion of chemical modification constraints improves the average accuracy from 28% to 78%. For the 11 sequences with <6% pseudoknotted base pairs, structures predicted with constraints from chemical modification contain on average 84% of known canonical base pairs. PMID:15123812

  17. Species-specific predictive models of developmental toxicity using the ToxCast chemical library

    EPA Science Inventory

    EPA’s ToxCastTM project is profiling the in vitro bioactivity of chemicals to generate predictive models that correlate with observed in vivo toxicity. In vitro profiling methods are based on ToxCast data, consisting of over 600 high-throughput screening (HTS) and high-content sc...

  18. Prediction of chemical contaminants and food compositions by near infrared spectroscopy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prediction of Food Adulteration by Infrared Spectroscopy H. Zhuang Quality and Safety Assessment Research Unit, ARS-USDA, 950 College Station Road, Athens, GA 30605 Food adulteration, including both chemical contamination and composition alternation, has been one of major quality and/or safety c...

  19. Species-Specific Predictive Signatures of Developmental Toxicity Using the ToxCast Chemical Library

    EPA Science Inventory

    EPA’s ToxCastTM project is profiling the in vitro bioactivity of chemicals to generate predictive signatures that correlate with observed in vivo toxicity. In vitro profiling methods from ToxCast data consist of over 600 high-throughput screening (HTS) and high-content screening ...

  20. Drug-target interaction prediction by integrating chemical, genomic, functional and pharmacological data.

    PubMed

    Yang, Fan; Xu, Jinbo; Zeng, Jianyang

    2014-01-01

    In silico prediction of unknown drug-target interactions (DTIs) has become a popular tool for drug repositioning and drug development. A key challenge in DTI prediction lies in integrating multiple types of data for accurate DTI prediction. Although recent studies have demonstrated that genomic, chemical and pharmacological data can provide reliable information for DTI prediction, it remains unclear whether functional information on proteins can also contribute to this task. Little work has been developed to combine such information with other data to identify new interactions between drugs and targets. In this paper, we introduce functional data into DTI prediction and construct biological space for targets using the functional similarity measure. We present a probabilistic graphical model, called conditional random field (CRF), to systematically integrate genomic, chemical, functional and pharmacological data plus the topology of DTI networks into a unified framework to predict missing DTIs. Tests on two benchmark datasets show that our method can achieve excellent prediction performance with the area under the precision-recall curve (AUPR) up to 94.9. These results demonstrate that our CRF model can successfully exploit heterogeneous data to capture the latent correlations of DTIs, and thus will be practically useful for drug repositioning. Supplementary Material is available at http://iiis.tsinghua.edu.cn/~compbio/papers/psb2014/psb2014_sm.pdf. PMID:24297542

  1. Predictive models of cytotoxicity as mediated by exposure to chemicals or drugs.

    PubMed

    Moon, H; Cong, M

    2016-06-01

    Predicting cytotoxicity is a challenging task because of the complex biological mechanisms behind it. Cytotoxicity due to toxin - biologically produced poison - is known to play a substantial role in a disease process. Two objectives in this research are to derive robust general predictive cytotoxicity models to minimize unnecessary toxicity. The first objective is to build accurate predictive statistical models for cytotoxicity data based on lymphoblastoid cell lines obtained from in vitro studies. This could be an important step for accomplishing a goal in biomedecial/biophamarceutical research, by obtaining the best medical outcomes by minimizing toxicity in regard to a person's genetic profile. The second objective is to build predictive models to predict population-level cytotoxicity for unknown compounds based on chemical structural features. These two objectives were accomplished by a proposed variable selection process, the random forests, and the least absolute shrinkage and selection operator method. We achieved an excellent prediction result with the random forests algorithm using SNP markers from the proposed approach, having the smallest root mean squared error among the teams which participated in the DREAM Toxicogenetics Challenge. Since chemical compounds for drugs have great influence on human health, the predictive statistical models for these objectives could be helpful to government agencies in relevant decision-making. PMID:27442234

  2. QSAR model for human pregnane X receptor (PXR) binding: Screening of environmental chemicals and correlations with genotoxicity, endocrine disruption and teratogenicity

    SciTech Connect

    Dybdahl, Marianne Nikolov, Nikolai G.; Wedebye, Eva Bay; Jónsdóttir, Svava Ósk; Niemelä, Jay R.

    2012-08-01

    The pregnane X receptor (PXR) has a key role in regulating the metabolism and transport of structurally diverse endogenous and exogenous compounds. Activation of PXR has the potential to initiate adverse effects, causing drug–drug interactions, and perturbing normal physiological functions. Therefore, identification of PXR ligands would be valuable information for pharmaceutical and toxicological research. In the present study, we developed a quantitative structure–activity relationship (QSAR) model for the identification of PXR ligands using data based on a human PXR binding assay. A total of 631 molecules, representing a variety of chemical structures, constituted the training set of the model. Cross-validation of the model showed a sensitivity of 82%, a specificity of 85%, and a concordance of 84%. The developed model provided knowledge about molecular descriptors that may influence the binding of molecules to PXR. The model was used to screen a large inventory of environmental chemicals, of which 47% was found to be within domain of the model. Approximately 35% of the chemicals within domain were predicted to be PXR ligands. The predicted PXR ligands were found to be overrepresented among chemicals predicted to cause adverse effects, such as genotoxicity, teratogenicity, estrogen receptor activation and androgen receptor antagonism compared to chemicals not causing these effects. The developed model may be useful as a tool for predicting potential PXR ligands and for providing mechanistic information of toxic effects of chemicals. -- Highlights: ► Global QSAR model for the identification of PXR ligands was developed. ► Molecular descriptors that may influence PXR binding were identified. ► 35% of a large set of environmental chemicals were predicted to be PXR ligands. ► Predicted PXR binding was associated with various adverse effects.

  3. Biodiversity in environmental assessment-current practice and tools for prediction

    SciTech Connect

    Gontier, Mikael . E-mail: gontier@kth.se; Balfors, Berit . E-mail: balfors@kth.se; Moertberg, Ulla . E-mail: mortberg@kth.se

    2006-04-15

    Habitat loss and fragmentation are major threats to biodiversity. Environmental impact assessment and strategic environmental assessment are essential instruments used in physical planning to address such problems. Yet there are no well-developed methods for quantifying and predicting impacts of fragmentation on biodiversity. In this study, a literature review was conducted on GIS-based ecological models that have potential as prediction tools for biodiversity assessment. Further, a review of environmental impact statements for road and railway projects from four European countries was performed, to study how impact prediction concerning biodiversity issues was addressed. The results of the study showed the existing gap between research in GIS-based ecological modelling and current practice in biodiversity assessment within environmental assessment.

  4. Prediction of aged red wine aroma properties from aroma chemical composition. Partial least squares regression models.

    PubMed

    Aznar, Margarita; López, Ricardo; Cacho, Juan; Ferreira, Vicente

    2003-04-23

    Partial least squares regression (PLSR) models able to predict some of the wine aroma nuances from its chemical composition have been developed. The aromatic sensory characteristics of 57 Spanish aged red wines were determined by 51 experts from the wine industry. The individual descriptions given by the experts were recorded, and the frequency with which a sensory term was used to define a given wine was taken as a measurement of its intensity. The aromatic chemical composition of the wines was determined by already published gas chromatography (GC)-flame ionization detector and GC-mass spectrometry methods. In the whole, 69 odorants were analyzed. Both matrixes, the sensory and chemical data, were simplified by grouping and rearranging correlated sensory terms or chemical compounds and by the exclusion of secondary aroma terms or of weak aroma chemicals. Finally, models were developed for 18 sensory terms and 27 chemicals or groups of chemicals. Satisfactory models, explaining more than 45% of the original variance, could be found for nine of the most important sensory terms (wood-vanillin-cinnamon, animal-leather-phenolic, toasted-coffee, old wood-reduction, vegetal-pepper, raisin-flowery, sweet-candy-cacao, fruity, and berry fruit). For this set of terms, the correlation coefficients between the measured and predicted Y (determined by cross-validation) ranged from 0.62 to 0.81. Models confirmed the existence of complex multivariate relationships between chemicals and odors. In general, pleasant descriptors were positively correlated to chemicals with pleasant aroma, such as vanillin, beta damascenone, or (E)-beta-methyl-gamma-octalactone, and negatively correlated to compounds showing less favorable odor properties, such as 4-ethyl and vinyl phenols, 3-(methylthio)-1-propanol, or phenylacetaldehyde.

  5. Prediction of aqueous solubility, vapor pressure and critical micelle concentration for aquatic partitioning of perfluorinated chemicals.

    PubMed

    Bhhatarai, Barun; Gramatica, Paola

    2011-10-01

    The majority of perfluorinated chemicals (PFCs) are of increasing risk to biota and environment due to their physicochemical stability, wide transport in the environment and difficulty in biodegradation. It is necessary to identify and prioritize these harmful PFCs and to characterize their physicochemical properties that govern the solubility, distribution and fate of these chemicals in an aquatic ecosystem. Therefore, available experimental data (10-35 compounds) of three important properties: aqueous solubility (AqS), vapor pressure (VP) and critical micelle concentration (CMC) on per- and polyfluorinated compounds were collected for quantitative structure-property relationship (QSPR) modeling. Simple and robust models based on theoretical molecular descriptors were developed and externally validated for predictivity. Model predictions on selected PFCs were compared with available experimental data and other published in silico predictions. The structural applicability domains (AD) of the models were verified on a bigger data set of 221 compounds. The predicted properties of the chemicals that are within the AD, are reliable, and they help to reduce the wide data gap that exists. Moreover, the predictions of AqS, VP, and CMC of most common PFCs were evaluated to understand the aquatic partitioning and to derive a relation with the available experimental data of bioconcentration factor (BCF).

  6. Effect of Weather on the Predicted PMN Landmine Chemical Signature for Kabul, Afghanistan

    SciTech Connect

    WEBB, STEPHEN W.; PHELAN, JAMES M.

    2002-11-01

    Buried landmines are often detected through the chemical signature in the air above the soil surface by mine detection dogs. Environmental processes play a significant role in the chemical signature available for detection. Due to the shallow burial depth of landmines, the weather influences the release of chemicals from the landmine, transport through the soil to the surface, and degradation processes in the soil. The effect of weather on the landmine chemical signature from a PMN landmine was evaluated with the T2TNT code for Kabul, Afghanistan. Results for TNT and DNT gas-phase and soil solid-phase concentrations are presented as a function of time of the day and time of the year.

  7. PREDICTION METRICS FOR CHEMICAL DETECTION IN LONG-WAVE INFRARED HYPERSPECTRAL IMAGERY

    SciTech Connect

    Chilton, M.; Walsh, S.J.; Daly, D.S.

    2009-01-01

    Natural and man-made chemical processes generate gaseous plumes that may be detected by hyperspectral imaging, which produces a matrix of spectra affected by the chemical constituents of the plume, the atmosphere, the bounding background surface and instrument noise. A physics-based model of observed radiance shows that high chemical absorbance and low background emissivity result in a larger chemical signature. Using simulated hyperspectral imagery, this study investigated two metrics which exploited this relationship. The objective was to explore how well the chosen metrics predicted when a chemical would be more easily detected when comparing one background type to another. The two predictor metrics correctly rank ordered the backgrounds for about 94% of the chemicals tested as compared to the background rank orders from Whitened Matched Filtering (a detection algorithm) of the simulated spectra. These results suggest that the metrics provide a reasonable summary of how the background emissivity and chemical absorbance interact to produce the at-sensor chemical signal. This study suggests that similarly effective predictors that account for more general physical conditions may be derived.

  8. A multi-scale, multi-disciplinary approach for assessing the technological, economic and environmental performance of bio-based chemicals.

    PubMed

    Herrgård, Markus; Sukumara, Sumesh; Campodonico, Miguel; Zhuang, Kai

    2015-12-01

    In recent years, bio-based chemicals have gained interest as a renewable alternative to petrochemicals. However, there is a significant need to assess the technological, biological, economic and environmental feasibility of bio-based chemicals, particularly during the early research phase. Recently, the Multi-scale framework for Sustainable Industrial Chemicals (MuSIC) was introduced to address this issue by integrating modelling approaches at different scales ranging from cellular to ecological scales. This framework can be further extended by incorporating modelling of the petrochemical value chain and the de novo prediction of metabolic pathways connecting existing host metabolism to desirable chemical products. This multi-scale, multi-disciplinary framework for quantitative assessment of bio-based chemicals will play a vital role in supporting engineering, strategy and policy decisions as we progress towards a sustainable chemical industry.

  9. A multi-scale, multi-disciplinary approach for assessing the technological, economic and environmental performance of bio-based chemicals.

    PubMed

    Herrgård, Markus; Sukumara, Sumesh; Campodonico, Miguel; Zhuang, Kai

    2015-12-01

    In recent years, bio-based chemicals have gained interest as a renewable alternative to petrochemicals. However, there is a significant need to assess the technological, biological, economic and environmental feasibility of bio-based chemicals, particularly during the early research phase. Recently, the Multi-scale framework for Sustainable Industrial Chemicals (MuSIC) was introduced to address this issue by integrating modelling approaches at different scales ranging from cellular to ecological scales. This framework can be further extended by incorporating modelling of the petrochemical value chain and the de novo prediction of metabolic pathways connecting existing host metabolism to desirable chemical products. This multi-scale, multi-disciplinary framework for quantitative assessment of bio-based chemicals will play a vital role in supporting engineering, strategy and policy decisions as we progress towards a sustainable chemical industry. PMID:26614653

  10. Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy.

    PubMed

    Cooke, Gerard M

    2014-01-01

    The first trimester of human fetal life, a period of extremely rapid development of physiological systems, represents the most rapid growth phase in human life. Interference in the establishment of organ systems may result in abnormal development that may be manifest immediately or programmed for later abnormal function. Exposure to environmental chemicals may be affecting development at these early stages, and yet there is limited knowledge of the quantities and identities of the chemicals to which the fetus is exposed during early pregnancy. Clearly, opportunities for assessing fetal chemical exposure directly are extremely limited. Hence, this review describes indirect means of assessing fetal exposure in early pregnancy to chemicals that are considered disrupters of development. Consideration is given to such matrices as maternal hair, fingernails, urine, saliva, sweat, breast milk, amniotic fluid and blood, and fetal matrices such as cord blood, cord tissue, meconium, placenta, and fetal liver. More than 150 articles that presented data from chemical analysis of human maternal and fetal tissues and fluids were reviewed. Priority was given to articles where chemical analysis was conducted in more than one matrix. Where correlations between maternal and fetal matrices were determined, these articles were included and are highlighted, as these may provide the basis for future investigations of early fetal exposure. The determination of fetal chemical exposure, at the time of rapid human growth and development, will greatly assist regulatory agencies in risk assessments and establishment of advisories for risk management concerning environmental chemicals.

  11. Protein backbone and sidechain torsion angles predicted from NMR chemical shifts using artificial neural networks.

    PubMed

    Shen, Yang; Bax, Ad

    2013-07-01

    A new program, TALOS-N, is introduced for predicting protein backbone torsion angles from NMR chemical shifts. The program relies far more extensively on the use of trained artificial neural networks than its predecessor, TALOS+. Validation on an independent set of proteins indicates that backbone torsion angles can be predicted for a larger, ≥90 % fraction of the residues, with an error rate smaller than ca 3.5 %, using an acceptance criterion that is nearly two-fold tighter than that used previously, and a root mean square difference between predicted and crystallographically observed (ϕ, ψ) torsion angles of ca 12º. TALOS-N also reports sidechain χ(1) rotameric states for about 50 % of the residues, and a consistency with reference structures of 89 %. The program includes a neural network trained to identify secondary structure from residue sequence and chemical shifts.

  12. Predicting changes in the distribution and abundance of species under environmental change

    PubMed Central

    Ehrlén, Johan; Morris, William F

    2015-01-01

    Environmental changes are expected to alter both the distribution and the abundance of organisms. A disproportionate amount of past work has focused on distribution only, either documenting historical range shifts or predicting future occurrence patterns. However, simultaneous predictions of abundance and distribution across landscapes would be far more useful. To critically assess which approaches represent advances towards the goal of joint predictions of abundance and distribution, we review recent work on changing distributions and on effects of environmental drivers on single populations. Several methods have been used to predict changing distributions. Some of these can be easily modified to also predict abundance, but others cannot. In parallel, demographers have developed a much better understanding of how changing abiotic and biotic drivers will influence growth rate and abundance in single populations. However, this demographic work has rarely taken a landscape perspective and has largely ignored the effects of intraspecific density. We advocate a synthetic approach in which population models accounting for both density dependence and effects of environmental drivers are used to make integrated predictions of equilibrium abundance and distribution across entire landscapes. Such predictions would constitute an important step forward in assessing the ecological consequences of environmental changes. PMID:25611188

  13. Predicting changes in the distribution and abundance of species under environmental change.

    PubMed

    Ehrlén, Johan; Morris, William F

    2015-03-01

    Environmental changes are expected to alter both the distribution and the abundance of organisms. A disproportionate amount of past work has focused on distribution only, either documenting historical range shifts or predicting future occurrence patterns. However, simultaneous predictions of abundance and distribution across landscapes would be far more useful. To critically assess which approaches represent advances towards the goal of joint predictions of abundance and distribution, we review recent work on changing distributions and on effects of environmental drivers on single populations. Several methods have been used to predict changing distributions. Some of these can be easily modified to also predict abundance, but others cannot. In parallel, demographers have developed a much better understanding of how changing abiotic and biotic drivers will influence growth rate and abundance in single populations. However, this demographic work has rarely taken a landscape perspective and has largely ignored the effects of intraspecific density. We advocate a synthetic approach in which population models accounting for both density dependence and effects of environmental drivers are used to make integrated predictions of equilibrium abundance and distribution across entire landscapes. Such predictions would constitute an important step forward in assessing the ecological consequences of environmental changes.

  14. Predicting changes in the distribution and abundance of species under environmental change.

    PubMed

    Ehrlén, Johan; Morris, William F

    2015-03-01

    Environmental changes are expected to alter both the distribution and the abundance of organisms. A disproportionate amount of past work has focused on distribution only, either documenting historical range shifts or predicting future occurrence patterns. However, simultaneous predictions of abundance and distribution across landscapes would be far more useful. To critically assess which approaches represent advances towards the goal of joint predictions of abundance and distribution, we review recent work on changing distributions and on effects of environmental drivers on single populations. Several methods have been used to predict changing distributions. Some of these can be easily modified to also predict abundance, but others cannot. In parallel, demographers have developed a much better understanding of how changing abiotic and biotic drivers will influence growth rate and abundance in single populations. However, this demographic work has rarely taken a landscape perspective and has largely ignored the effects of intraspecific density. We advocate a synthetic approach in which population models accounting for both density dependence and effects of environmental drivers are used to make integrated predictions of equilibrium abundance and distribution across entire landscapes. Such predictions would constitute an important step forward in assessing the ecological consequences of environmental changes. PMID:25611188

  15. Extended Characterization of Chemical Processes in Hot Cells Using Environmental Swipe Samples

    SciTech Connect

    Olsen, Khris B.; Mitroshkov, Alexandre V.; Thomas, M-L; Lepel, Elwood A.; Brunson, Ronald R.; Ladd-Lively, Jennifer

    2012-09-15

    Environmental sampling is used extensively by the International Atomic Energy Agency (IAEA) for verification of information from State declarations or a facility’s design regarding nuclear activities occurring within the country or a specific facility. Environmental sampling of hot cells within a facility under safeguards is conducted using 10.2 cm x 10.2 cm cotton swipe material or cellulose swipes. Traditional target analytes used by the IAEA to verify operations within a facility include a select list of gamma-emitting radionuclides and total and isotopic U and Pu. Analysis of environmental swipe samples collected within a hot-cell facility where chemical processing occurs may also provide information regarding specific chemicals used in fuel processing. However, using swipe material to elucidate what specific chemical processes were/are being used within a hot cell has not been previously evaluated. Staff from Pacific Northwest National Laboratory (PNNL) and Oak Ridge National Laboratory (ORNL) teamed to evaluate the potential use of environmental swipe samples as collection media for volatile and semivolatile organic compounds. This evaluation was initiated with sample collection during a series of Coupled End-to-End (CETE) reprocessing runs at ORNL. The study included measurement of gamma emitting radionuclides, total and isotopic U and Pu, and volatile and semivolatile organic compounds. These results allowed us to elucidate what chemical processes used in the hot cells during reprocessing of power reactor and identify other legacy chemicals used in hot cell operations which predate the CETE process.

  16. Study of improved methods for predicting chemical equilibria. Final technical report, April 1, 1993--August 31, 1997

    SciTech Connect

    Lenz, T.G.; Vaughan, J.D.

    1997-10-01

    A long-standing goal of chemical engineers and chemists has been the development of techniques for accurate prediction of the thermodynamic properties of isolated molecules. The thermochemical functions for an ideal gas then provide a means of computing chemical equilibria, and such computations can be extended to condensed phase chemical equilibria with appropriate physical property data. Such capability for predicting diverse chemical equilibria is important in today`s competitive international economic environment, where bringing new products to market rapidly and efficiently is crucial. The purpose of this project has been to develop such computational methods for predicting chemical equilibria.

  17. Nonradiological chemical pathway analysis and identification of chemicals of concern for environmental monitoring at the Hanford Site

    SciTech Connect

    Blanton, M.L.; Cooper, A.T.; Castleton, K.J.

    1995-11-01

    Pacific Northwest`s Surface Environmental Surveillance Project (SESP) is an ongoing effort tot design, review, and conducted monitoring on and off the Hanford site. Chemicals of concern that were selected are listed. Using modeled exposure pathways, the offsite cancer incidence and hazard quotient were calculated and a retrospective pathway analysis performed to estimate what onsite concentrations would be required in the soil for each chemical of concern and other detected chemicals that would be required to obtain an estimated offsite human-health risk of 1.0E-06 cancer incidence or 1.0 hazard quotient. This analysis indicates that current nonradiological chemical contamination occurring on the site does not pose a significant offsite human-health risk; the highest cancer incidence to the offsite maximally exposed individual was from arsenic (1.76E-10); the highest hazard quotient was chromium(VI) (1.48E-04). The most sensitive pathways of exposure were surfacewater and aquatic food consumption. Combined total offsite excess cancer incidence was 2.09E-10 and estimated hazard quotient was 2.40E-04. Of the 17 identified chemicals of concern, the SESP does not currently (routinely) monitor arsenic, benzo(a)pyrene, bis(2- ethylhexyl)phthalate (BEHP), and chrysene. Only 3 of the chemicals of concern (arsenic, BEHP, chloroform) could actually occur in onsite soil at concern high enough to cause a 1.0E-06 excess cancer incidence or a 1.0 hazard index for a given offsite exposure pathway. During the retrospective analysis, 20 other chemicals were also evaluated; only vinyl chloride and thallium could reach targeted offsite risk values.

  18. IDENTIFICATION OF ENVIRONMENTAL CHEMICALS ASSOCIATED WITH THE DEVELOPMENT OF TOXICANT ASSOCIATED FATTY LIVER DISEASE IN RODENTS

    PubMed Central

    Al-Eryani, Laila; Wahlang, Banrida; Falkner, K.C.; Guardiola, J. J.; Clair, H.B.; Prough, R.A.; Cave, M.

    2014-01-01

    Background Toxicant associated fatty liver disease (TAFLD) is a recently identified form of non-alcoholic fatty liver disease (NAFLD) associated with exposure to industrial chemicals and environmental pollutants. Numerous studies have been conducted to test the association between industrial chemicals/ environmental pollutants and fatty liver disease both in vivo and in vitro. Objectives The objective of the paper is to report a list of chemicals associated with TAFLD. Methods Two federal databases of rodent toxicology studies– ToxRefDB (Environmental Protection Agency) and Chemical Effects in Biological Systems (CEBS, National Toxicology Program) were searched for liver endpoints. Combined, these two databases archive nearly 2000 rodent studies. TASH descriptors including fatty change, fatty necrosis, Oil red O positive staining, steatosis and lipid deposition were queried. Results Using these search terms, 123 chemicals associated with fatty liver were identified. Pesticides and solvents were the most frequently identified chemicals, while PCBs/dioxins were the most potent. About 44% of identified compounds were pesticides or their intermediates, and nearly 10% of pesticide registration studies in ToxRefDB were associated with fatty liver. Fungicides and herbicides were more frequently associated with fatty liver than insecticides. Conclusions More research on pesticides, solvents, metals and PCBs/dioxins in NAFLD/TAFLD is warranted due to their association with liver damage. PMID:25326588

  19. DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders?

    PubMed Central

    Keil, Kimberly P.; Lein, Pamela J.

    2016-01-01

    There is now compelling evidence that gene by environment interactions are important in the etiology of autism spectrum disorders (ASDs). However, the mechanisms by which environmental factors interact with genetic susceptibilities to confer individual risk for ASD remain a significant knowledge gap in the field. The epigenome, and in particular DNA methylation, is a critical gene expression regulatory mechanism in normal and pathogenic brain development. DNA methylation can be influenced by environmental factors such as diet, hormones, stress, drugs, or exposure to environmental chemicals, suggesting that environmental factors may contribute to adverse neurodevelopmental outcomes of relevance to ASD via effects on DNA methylation in the developing brain. In this review, we describe epidemiological and experimental evidence implicating altered DNA methylation as a potential mechanism by which environmental chemicals confer risk for ASD, using polychlorinated biphenyls (PCBs), lead, and bisphenol A (BPA) as examples. Understanding how environmental chemical exposures influence DNA methylation and how these epigenetic changes modulate the risk and/or severity of ASD will not only provide mechanistic insight regarding gene-environment interactions of relevance to ASD but may also suggest potential intervention strategies for these and potentially other neurodevelopmental disorders. PMID:27158529

  20. Endocrine Profiling and Prioritization of Environmental Chemicals Using ToxCast Data

    PubMed Central

    Reif, David M.; Martin, Matthew T.; Tan, Shirlee W.; Houck, Keith A.; Judson, Richard S.; Richard, Ann M.; Knudsen, Thomas B.; Dix, David J.; Kavlock, Robert J.

    2010-01-01

    Background The prioritization of chemicals for toxicity testing is a primary goal of the U.S. Environmental Protection Agency (EPA) ToxCast™ program. Phase I of ToxCast used a battery of 467 in vitro, high-throughput screening assays to assess 309 environmental chemicals. One important mode of action leading to toxicity is endocrine disruption, and the U.S. EPA’s Endocrine Disruptor Screening Program (EDSP) has been charged with screening pesticide chemicals and environmental contaminants for their potential to affect the endocrine systems of humans and wildlife. Objective The goal of this study was to develop a flexible method to facilitate the rational prioritization of chemicals for further evaluation and demonstrate its application as a candidate decision-support tool for EDSP. Methods Focusing on estrogen, androgen, and thyroid pathways, we defined putative endocrine profiles and derived a relative rank or score for the entire ToxCast library of 309 unique chemicals. Effects on other nuclear receptors and xenobiotic metabolizing enzymes were also considered, as were pertinent chemical descriptors and pathways relevant to endocrine-mediated signaling. Results Combining multiple data sources into an overall, weight-of-evidence Toxicological Priority Index (ToxPi) score for prioritizing further chemical testing resulted in more robust conclusions than any single data source taken alone. Conclusions Incorporating data from in vitro assays, chemical descriptors, and biological pathways in this prioritization schema provided a flexible, comprehensive visualization and ranking of each chemical’s potential endocrine activity. Importantly, ToxPi profiles provide a transparent visualization of the relative contribution of all information sources to an overall priority ranking. The method developed here is readily adaptable to diverse chemical prioritization tasks. PMID:20826373

  1. Prediction Metrics for Chemical Detection in Long-Wave Infrared Hyperspectral Imagery

    SciTech Connect

    Chilton, Marie C.; Walsh, Stephen J.; Daly, Don S.

    2009-01-29

    A natural or anthropogenic process often generates a signature gas plume whose chemical constituents may be identified using hyperspectral imagery. A hyperspectral image is a pixel-indexed set of spectra where each spectrum reflects the chemical constituents of the plume, the atmosphere, the bounding background surface, and instrument noise. This study explored the relationship between gas absorbance and background emissivity across the long-wave infrared (LWIR) spectrum and how they affect relative gas detection sensitivity. The physics-based model for the observed radiance shows that high gas absorbance coupled with low background emissivity at a single wavenumber results in a stronger recorded radiance. Two sensitivity measures were developed to predict relative probability of detection using chemical absorbance and background emissivity: one focused on a single wavenumber while another accounted for the entire spectrum. The predictive abilities of these measures were compared to synthetic image analysis. This study simulated images with 499 distinct gases at each of 6 concentrations over 6 different background surfaces with the atmosphere and level of instrument noise held constant. The Whitened Matched Filter was used to define gas detection from an image spectrum. The estimate of a chemical’s probability of detection at a given concentration over a specific background was the proportion of detections in 500 trials. Of the 499 chemicals used in the images, 276 had estimated probabilities of detection below 0.2 across all backgrounds and concentrations; these chemicals were removed from the study. For 92.8 percent of the remaining chemicals, the single channel measure correctly predicted the background over which the chemical had the largest relative probability of detection. Further, the measure which accounted for information across all wavenumbers predicted the background over which the chemical had the largest relative probability of detection for 93

  2. Predicting the risk of toxic blooms of golden alga from cell abundance and environmental covariates

    USGS Publications Warehouse

    Patino, Reynaldo; VanLandeghem, Matthew M.; Denny, Shawn

    2016-01-01

    Golden alga (Prymnesium parvum) is a toxic haptophyte that has caused considerable ecological damage to marine and inland aquatic ecosystems worldwide. Studies focused primarily on laboratory cultures have indicated that toxicity is poorly correlated with the abundance of golden alga cells. This relationship, however, has not been rigorously evaluated in the field where environmental conditions are much different. The ability to predict toxicity using readily measured environmental variables and golden alga abundance would allow managers rapid assessments of ichthyotoxicity potential without laboratory bioassay confirmation, which requires additional resources to accomplish. To assess the potential utility of these relationships, several a priori models relating lethal levels of golden alga ichthyotoxicity to golden alga abundance and environmental covariates were constructed. Model parameters were estimated using archived data from four river basins in Texas and New Mexico (Colorado, Brazos, Red, Pecos). Model predictive ability was quantified using cross-validation, sensitivity, and specificity, and the relative ranking of environmental covariate models was determined by Akaike Information Criterion values and Akaike weights. Overall, abundance was a generally good predictor of ichthyotoxicity as cross validation of golden alga abundance-only models ranged from ∼ 80% to ∼ 90% (leave-one-out cross-validation). Environmental covariates improved predictions, especially the ability to predict lethally toxic events (i.e., increased sensitivity), and top-ranked environmental covariate models differed among the four basins. These associations may be useful for monitoring as well as understanding the abiotic factors that influence toxicity during blooms.

  3. Machine Learning Predictions of Molecular Properties: Accurate Many-Body Potentials and Nonlocality in Chemical Space.

    PubMed

    Hansen, Katja; Biegler, Franziska; Ramakrishnan, Raghunathan; Pronobis, Wiktor; von Lilienfeld, O Anatole; Müller, Klaus-Robert; Tkatchenko, Alexandre

    2015-06-18

    Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical industries. Aiming toward this goal, we develop and apply a systematic hierarchy of efficient empirical methods to estimate atomization and total energies of molecules. These methods range from a simple sum over atoms, to addition of bond energies, to pairwise interatomic force fields, reaching to the more sophisticated machine learning approaches that are capable of describing collective interactions between many atoms or bonds. In the case of equilibrium molecular geometries, even simple pairwise force fields demonstrate prediction accuracy comparable to benchmark energies calculated using density functional theory with hybrid exchange-correlation functionals; however, accounting for the collective many-body interactions proves to be essential for approaching the “holy grail” of chemical accuracy of 1 kcal/mol for both equilibrium and out-of-equilibrium geometries. This remarkable accuracy is achieved by a vectorized representation of molecules (so-called Bag of Bonds model) that exhibits strong nonlocality in chemical space. In addition, the same representation allows us to predict accurate electronic properties of molecules, such as their polarizability and molecular frontier orbital energies.

  4. Phenotypic side effects prediction by optimizing correlation with chemical and target profiles of drugs.

    PubMed

    Kanji, Rakesh; Sharma, Abhinav; Bagler, Ganesh

    2015-11-01

    Despite technological progresses and improved understanding of biological systems, discovery of novel drugs is an inefficient, arduous and expensive process. Research and development cost of drugs is unreasonably high, largely attributed to the high attrition rate of candidate drugs due to adverse drug reactions. Computational methods for accurate prediction of drug side effects, rooted in empirical data of drugs, have the potential to enhance the efficacy of the drug discovery process. Identification of features critical for specifying side effects would facilitate efficient computational procedures for their prediction. We devised a generalized ordinary canonical correlation model for prediction of drug side effects based on their chemical properties as well as their target profiles. While the former is based on 2D and 3D chemical features, the latter enumerates a systems-level property of drugs. We find that the model incorporating chemical features outperforms that incorporating target profiles. Furthermore we identified the 2D and 3D chemical properties that yield best results, thereby implying their relevance in specifying adverse drug reactions. PMID:26252576

  5. Machine learning predictions of molecular properties: Accurate many-body potentials and nonlocality in chemical space

    SciTech Connect

    Hansen, Katja; Biegler, Franziska; Ramakrishnan, Raghunathan; Pronobis, Wiktor; von Lilienfeld, O. Anatole; Müller, Klaus -Robert; Tkatchenko, Alexandre

    2015-06-04

    Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical industries. Aiming toward this goal, we develop and apply a systematic hierarchy of efficient empirical methods to estimate atomization and total energies of molecules. These methods range from a simple sum over atoms, to addition of bond energies, to pairwise interatomic force fields, reaching to the more sophisticated machine learning approaches that are capable of describing collective interactions between many atoms or bonds. In the case of equilibrium molecular geometries, even simple pairwise force fields demonstrate prediction accuracy comparable to benchmark energies calculated using density functional theory with hybrid exchange-correlation functionals; however, accounting for the collective many-body interactions proves to be essential for approaching the “holy grail” of chemical accuracy of 1 kcal/mol for both equilibrium and out-of-equilibrium geometries. This remarkable accuracy is achieved by a vectorized representation of molecules (so-called Bag of Bonds model) that exhibits strong nonlocality in chemical space. The same representation allows us to predict accurate electronic properties of molecules, such as their polarizability and molecular frontier orbital energies.

  6. Machine learning predictions of molecular properties: Accurate many-body potentials and nonlocality in chemical space

    DOE PAGESBeta

    Hansen, Katja; Biegler, Franziska; Ramakrishnan, Raghunathan; Pronobis, Wiktor; von Lilienfeld, O. Anatole; Müller, Klaus -Robert; Tkatchenko, Alexandre

    2015-06-04

    Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical industries. Aiming toward this goal, we develop and apply a systematic hierarchy of efficient empirical methods to estimate atomization and total energies of molecules. These methods range from a simple sum over atoms, to addition of bond energies, to pairwise interatomic force fields, reaching to the more sophisticated machine learning approaches that are capable of describing collective interactions between many atoms or bonds. In the case of equilibrium molecular geometries, even simple pairwise force fields demonstratemore » prediction accuracy comparable to benchmark energies calculated using density functional theory with hybrid exchange-correlation functionals; however, accounting for the collective many-body interactions proves to be essential for approaching the “holy grail” of chemical accuracy of 1 kcal/mol for both equilibrium and out-of-equilibrium geometries. This remarkable accuracy is achieved by a vectorized representation of molecules (so-called Bag of Bonds model) that exhibits strong nonlocality in chemical space. The same representation allows us to predict accurate electronic properties of molecules, such as their polarizability and molecular frontier orbital energies.« less

  7. Machine Learning Predictions of Molecular Properties: Accurate Many-Body Potentials and Nonlocality in Chemical Space

    PubMed Central

    2015-01-01

    Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical industries. Aiming toward this goal, we develop and apply a systematic hierarchy of efficient empirical methods to estimate atomization and total energies of molecules. These methods range from a simple sum over atoms, to addition of bond energies, to pairwise interatomic force fields, reaching to the more sophisticated machine learning approaches that are capable of describing collective interactions between many atoms or bonds. In the case of equilibrium molecular geometries, even simple pairwise force fields demonstrate prediction accuracy comparable to benchmark energies calculated using density functional theory with hybrid exchange-correlation functionals; however, accounting for the collective many-body interactions proves to be essential for approaching the “holy grail” of chemical accuracy of 1 kcal/mol for both equilibrium and out-of-equilibrium geometries. This remarkable accuracy is achieved by a vectorized representation of molecules (so-called Bag of Bonds model) that exhibits strong nonlocality in chemical space. In addition, the same representation allows us to predict accurate electronic properties of molecules, such as their polarizability and molecular frontier orbital energies. PMID:26113956

  8. Role of Environmental Chemicals in Diabetes and Obesity: A National Toxicology Program Workshop Review

    PubMed Central

    Heindel, Jerrold J.; Bucher, John R.; Gallo, Michael A.

    2012-01-01

    Background: There has been increasing interest in the concept that exposures to environmental chemicals may be contributing factors to the epidemics of diabetes and obesity. On 11–13 January 2011, the National Institute of Environmental Health Sciences (NIEHS) Division of the National Toxicology Program (NTP) organized a workshop to evaluate the current state of the science on these topics of increasing public health concern. Objective: The main objective of the workshop was to develop recommendations for a research agenda after completing a critical analysis of the literature for humans and experimental animals exposed to certain environmental chemicals. The environmental exposures considered at the workshop were arsenic, persistent organic pollutants, maternal smoking/nicotine, organotins, phthalates, bisphenol A, and pesticides. High-throughput screening data from Toxicology in the 21st Century (Tox21) were also considered as a way to evaluate potential cellular pathways and generate -hypotheses for testing which and how certain chemicals might perturb biological processes related to diabetes and obesity. Conclusions: Overall, the review of the existing literature identified linkages between several of the environmental exposures and type 2 diabetes. There was also support for the “developmental obesogen” hypothesis, which suggests that chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes or the development of neural circuits that regulate feeding behavior. The effects may be most apparent when the developmental exposure is combined with consumption of a high-calorie, high-carbohydrate, or high-fat diet later in life. Research on environmental chemical exposures and type 1 diabetes was very limited. This lack of research was considered a critical data gap. In this workshop review, we outline the major themes that emerged from the workshop and discuss activities that NIEHS/NTP is undertaking to address research

  9. Incorporating transgenerational testing and epigenetic mechanisms into chemical testing and risk assessment: A survey of transgenerational responses in environmental chemical studies

    EPA Science Inventory

    A number of environmental chemicals have been shown to alter markers of epigenetic change. Some published multi-generation rodent studies have identified effects on F2 and greater generations after chemical exposures solely to F0 dams, but were not focused on chemical safety. We ...

  10. Chemical analysis of human blood for assessment of environmental exposure to semivolatile organochlorine chemical contaminants.

    PubMed

    Bristol, D W; Crist, H L; Lewis, R G; MacLeod, K E; Sovocool, G W

    1982-01-01

    A chemical method for the quantitative analysis of organochlorine pesticide residues present in human blood was scaled-up to provide increased sensitivity and extended to include organochlorine industrial chemicals. Whole blood samples were extracted with hexane, concentrated, and analyzed without further cleanup by gas chromatography with electron capture detection. The methodology used was validated by conducting recovery studies at 1 and 10 ng/g (ppb) levels. Screening and confirmational analyses were performed by gas chromatography/mass spectrometry on samples collected from potentially exposed residents of the Love Canal area of Niagara Falls, New York and from volunteers in the Research Triangle Park area of North Carolina for 25 specific semivolatile organochlorine contaminants including chlorobenzene and chlorotoluene congeners, hexachloro-1,3-butadiene, pesticides, and polychlorinated biphenyls as Aroclor 1260. Dichlorobenzene, hexachlorobenzene, and beta-hexachlorocyclohexane residues fell in the range of 0.1 to 26 ppb in a high percentage of both the field and volunteer blood samples analyzed. Levels of other organochlorine compounds were either non-detectable or present in sub-ppb ranges. PMID:6819409

  11. Prediction of carcinogenicity for diverse chemicals based on substructure grouping and SVM modeling.

    PubMed

    Tanabe, Kazutoshi; Lučić, Bono; Amić, Dragan; Kurita, Takio; Kaihara, Mikio; Onodera, Natsuo; Suzuki, Takahiro

    2010-11-01

    The Carcinogenicity Reliability Database (CRDB) was constructed by collecting experimental carcinogenicity data on about 1,500 chemicals from six sources, including IARC, and NTP databases, and then by ranking their reliabilities into six unified categories. A wide variety of 911 organic chemicals were selected from the database for QSAR modeling, and 1,504 kinds of different molecular descriptors were calculated, based on their 3D molecular structures as modeled by the Dragon software. Positive (carcinogenic) and negative (non-carcinogenic) chemicals containing various substructures were counted using atom and functional group count descriptors, and the statistical significance of ratios of positives to negatives was tested for those substructures. Very few were judged to be strongly related to carcinogenicity, among substructures known to be responsible for carcinogens as revealed from biomedical studies. In order to develop QSAR models for the prediction of the carcinogenicities of a wide variety of chemicals with a satisfactory performance level, the relationship between the carcinogenicity data with improved reliability and a subset of significant descriptors selected from 1,504 Dragon descriptors was analyzed with a support vector machine (SVM) method: the classification function (SVC) for weighted data in LIBSVM program was used to classify chemicals into two carcinogenic categories (positive or negative), where weights were set depending on the reliabilities of the carcinogenicity data. The quality and stability of the models presented were tested by performing a dual cross-validation procedure. A single SVM model as the first step was developed for all the 911 chemicals using 250 selected descriptors, achieving an overall accuracy level, i.e., positive and negative correct estimate, of about 70%. In order to improve the accuracy of the final model, the 911 chemicals were classified into 20 mutually overlapping subgroups according to contained substructures

  12. Quantitative structure-activity relationships for chemical toxicity to environmental bacteria

    SciTech Connect

    Blum, D.J.; Speece, R.E. )

    1991-10-01

    Quantitative structure-activity relationships (QSARs) were developed for nonreactive chemical toxicity to each of four groups of bacteria of importance in environmental engineering: aerobic heterotrophs, methanogens, Nitrosomonas, and Microtox. The QSARs were based on chemicals covering a range of structures and including important environmental pollutants (i.e., chlorinated and other substituted benzenes, phenols, and aliphatic hydrocarbons). QSARs were developed for each chemical class and for combinations of chemical classes. Three QSAR methods (groups of chemical describing parameters) were evaluated for their accuracy and ease of use: log P, linear solvation energy relationships (LSER), and molecular connectivity. Successful QSARs were found for each group of bacteria and by each method, with correlation coefficients (adjusted r2) between 0.79 and 0.95. LSER QSARs incorporated the widest range of chemicals with the greatest accuracy. Log P and molecular connectivity QSARs are easier to use because their parameters are readily available. Outliers from the QSARs likely due to reactive toxicity included acryls, low pKa compounds, and aldehydes. Nitro compounds and chlorinated aliphatic hydrocarbons and alcohols showed enhanced toxicity to the methanogens only. Chemicals with low IC50 concentrations (log IC50 mumol/liter less than 1.5) were often outliers for Nitrosomonas. QSARs were validated statistically and with literature data. A suggested method is provided for use of the QSARs.

  13. The EPC approach to estimating safety from exposure to environmental chemicals.

    PubMed

    Williams, C A; Jones, H D; Freeman, R W; Wernke, M J; Williams, P L; Roberts, S M; James, R C

    1994-12-01

    Reference doses (RfDs) and reference concentrations (RfCs) developed by the United States Environmental Protection Agency (USEPA) are typically used in the quantitation of risk of potential adverse human health effects from exposure to environmental chemicals. For a large number of chemicals, however, USEPA RfDs and RfCs have not yet been determined. Thus, for risk assessments that involve a large number of chemicals, there is insufficient toxicity information with which to evaluate potential adverse human health effects for all chemicals present at a particular site. Due to this insufficiency, the risk assessor must either (1) ignore potential exposures on the assumption that omitting these exposures does not significantly alter decisions concerning the remediation of the site or (2) undertake a lengthy and costly analysis to generate the necessary RfDs or RfCs. A potential solution to this problem is to develop estimated permissible concentrations (EPCs), values which represent permissible environmental concentrations or related acceptable daily dosages derived from occupational exposure limits. In the present analysis, acceptable daily dosages determined using the EPC method were compared to USEPA RfDs or RfCs which were converted to dosages based on standard exposure assumptions. Based on a comparative analysis of EPCs and USEPA reference values for 103 chemicals, it was found that EPC daily dosages represent a reasonably conservative surrogate value when USEPA or state reference values are unavailable. Given that there are hundreds of chemicals with occupational exposure limits but no state or USEPA reference values, acceptance of the EPC methodology would provide an interim solution for the problem of insufficient toxicity information for a substantial number of environmental chemical contaminants.

  14. An Energy Balance Model to Predict Chemical Partitioning in a Photosynthetic Microbial Mat

    NASA Technical Reports Server (NTRS)

    Hoehler, Tori M.; Albert, Daniel B.; DesMarais, David J.

    2006-01-01

    Studies of biosignature formation in photosynthetic microbial mat communities offer potentially useful insights with regards to both solar and extrasolar astrobiology. Biosignature formation in such systems results from the chemical transformation of photosynthetically fixed carbon by accessory microorganisms. This fixed carbon represents a source not only of reducing power, but also energy, to these organisms, so that chemical and energy budgets should be coupled. We tested this hypothesis by applying an energy balance model to predict the fate of photosynthetic productivity under dark, anoxic conditions. Fermentation of photosynthetically fixed carbon is taken to be the only source of energy available to cyanobacteria in the absence of light and oxygen, and nitrogen fixation is the principal energy demand. The alternate fate for fixed carbon is to build cyanobacterial biomass with Redfield C:N ratio. The model predicts that, under completely nitrogen-limited conditions, growth is optimized when 78% of fixed carbon stores are directed into fermentative energy generation, with the remainder allocated to growth. These predictions were compared to measurements made on microbial mats that are known to be both nitrogen-limited and populated by actively nitrogen-fixing cyanobacteria. In these mats, under dark, anoxic conditions, 82% of fixed carbon stores were diverted into fermentation. The close agreement between these independent approaches suggests that energy balance models may provide a quantitative means of predicting chemical partitioning within such systems - an important step towards understanding how biological productivity is ultimately partitioned into biosignature compounds.

  15. Prediction algorithm for amino acid types with their secondary structure in proteins (PLATON) using chemical shifts.

    PubMed

    Labudde, D; Leitner, D; Krüger, M; Oschkinat, H

    2003-01-01

    The algorithm PLATON is able to assign sets of chemical shifts derived from a single residue to amino acid types with its secondary structure (amino acid species). A subsequent ranking procedure using optionally two different penalty functions yields predictions for possible amino acid species for the given set of chemical shifts. This was demonstrated in the case of the alpha-spectrin SH3 domain and applied to 9 further protein data sets taken from the BioMagRes database. A database consisting of reference chemical shift patterns (reference CSPs) was generated from assigned chemical shifts of proteins with known 3D-structure. This reference CSP database is used in our approach for extracting distributions of amino acid types with their most likely secondary structure elements (namely alpha-helix, beta-sheet, and coil) for single amino acids by comparison with query CSPs. Results obtained for the 10 investigated proteins indicates that the percentage of correct amino acid species in the first three positions in the ranking list, ranges from 71.4% to 93.2% for the more favorable penalty function. Where only the top result of the ranking list for these 10 proteins is considered, 36.5% to 83.1% of the amino acid species are correctly predicted. The main advantage of our approach, over other methods that rely on average chemical shift values is the ability to increase database content by incorporating newly derived CSPs, and therefore to improve PLATON's performance over time.

  16. Oral LD50 toxicity modeling and prediction of per- and polyfluorinated chemicals on rat and mouse.

    PubMed

    Bhhatarai, Barun; Gramatica, Paola

    2011-05-01

    Quantitative structure-activity relationship (QSAR) analyses were performed using the LD(50) oral toxicity data of per- and polyfluorinated chemicals (PFCs) on rodents: rat and mouse. PFCs are studied under the EU project CADASTER which uses the available experimental data for prediction and prioritization of toxic chemicals for risk assessment by using the in silico tools. The methodology presented here applies chemometrical analysis on the existing experimental data and predicts the toxicity of new compounds. QSAR analyses were performed on the available 58 mouse and 50 rat LD(50) oral data using multiple linear regression (MLR) based on theoretical molecular descriptors selected by genetic algorithm (GA). Training and prediction sets were prepared a priori from available experimental datasets in terms of structure and response. These sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the models were verified on 376 per- and polyfluorinated chemicals including those in REACH preregistration list. The rat and mouse endpoints were predicted by each model for the studied compounds, and finally 30 compounds, all perfluorinated, were prioritized as most important for experimental toxicity analysis under the project. In addition, cumulative study on compounds within the AD of all four models, including two earlier published models on LC(50) rodent analysis was studied and the cumulative toxicity trend was observed using principal component analysis (PCA). The similarities and the differences observed in terms of descriptors and chemical/mechanistic meaning encoded by descriptors to prioritize the most toxic compounds are highlighted.

  17. Epigenome: Biosensor of Cumulative Exposure to Chemical and Nonchemical Stressors Related to Environmental Justice

    PubMed Central

    Gruber, David; Sonawane, Babasaheb

    2014-01-01

    Understanding differential disease susceptibility requires new tools to quantify the cumulative effects of environmental stress. Evidence suggests that social, physical, and chemical stressors can influence disease through the accumulation of epigenetic modifications. Geographically stable epigenetic alterations could identify plausible mechanisms for health disparities among the disadvantaged and poor. Relations between neighborhood-specific epigenetic markers and disease would identify the most appropriate targets for medical and environmental intervention. Complex interactions among genes, the environment, and disease require the examination of how epigenetic changes regulate susceptibility to environmental stressors. Progress in understanding disparities in disease susceptibility may depend on assessing the cumulative effect of environmental stressors on genetic substrates. We highlight key concepts regarding the interface between environmental stress, epigenetics, and chronic disease. PMID:25122010

  18. Epigenome: biosensor of cumulative exposure to chemical and nonchemical stressors related to environmental justice.

    PubMed

    Olden, Kenneth; Lin, Yu-Sheng; Gruber, David; Sonawane, Babasaheb

    2014-10-01

    Understanding differential disease susceptibility requires new tools to quantify the cumulative effects of environmental stress. Evidence suggests that social, physical, and chemical stressors can influence disease through the accumulation of epigenetic modifications. Geographically stable epigenetic alterations could identify plausible mechanisms for health disparities among the disadvantaged and poor. Relations between neighborhood-specific epigenetic markers and disease would identify the most appropriate targets for medical and environmental intervention. Complex interactions among genes, the environment, and disease require the examination of how epigenetic changes regulate susceptibility to environmental stressors. Progress in understanding disparities in disease susceptibility may depend on assessing the cumulative effect of environmental stressors on genetic substrates. We highlight key concepts regarding the interface between environmental stress, epigenetics, and chronic disease.

  19. Chemical genomic profiling via barcode sequencing to predict compound mode of action

    PubMed Central

    Piotrowski, Jeff S.; Simpkins, Scott W.; Li, Sheena C.; Deshpande, Raamesh; McIlwain, Sean; Ong, Irene; Myers, Chad L.; Boone, Charlie; Andersen, Raymond J.

    2015-01-01

    Summary Chemical genomics is an unbiased, whole-cell approach to characterizing novel compounds to determine mode of action and cellular target. Our version of this technique is built upon barcoded deletion mutants of Saccharomyces cerevisiae and has been adapted to a high-throughput methodology using next-generation sequencing. Here we describe the steps to generate a chemical genomic profile from a compound of interest, and how to use this information to predict molecular mechanism and targets of bioactive compounds. PMID:25618354

  20. Measurement and chemical kinetic model predictions of detonation cell size in methanol-oxygen mixtures

    NASA Astrophysics Data System (ADS)

    Eaton, R.; Zhang, B.; Bergthorson, J. M.; Ng, H. D.

    2012-03-01

    In this study, detonation cell sizes of methanol-oxygen mixtures are experimentally measured at different initial pressures and compositions. Good agreement is found between the experiment data and predictions based on the chemical length scales obtained from a detailed chemical kinetic model. To assess the detonation sensitivity in methanol-oxygen mixtures, the results are compared with those of hydrogen-oxygen and methane-oxygen mixtures. Based on the cell size comparison, it is shown that methanol-oxygen is more detonation sensitive than methane-oxygen but less sensitive than hydrogen-oxygen.

  1. CDRUG: a web server for predicting anticancer activity of chemical compounds.

    PubMed

    Li, Gong-Hua; Huang, Jing-Fei

    2012-12-15

    Cancer is the leading cause of death worldwide. Screening anticancer candidates from tens of millions of chemical compounds is expensive and time-consuming. A rapid and user-friendly web server, known as CDRUG, is described here to predict the anticancer activity of chemical compounds. In CDRUG, a hybrid score was developed to measure the similarity of different compounds. The performance analysis shows that CDRUG has the area under curve of 0.878, indicating that CDRUG is effective to distinguish active and inactive compounds.

  2. Systems Biology Approach for Understanding MOA, Dose-Response and Susceptibility to Environmental Chemicals

    EPA Science Inventory

    There is an increasing need for assays for the rapid and efficient assessment of toxicities of large numbers of environmental chemicals. To meet this need, we have developed a battery of cell-based reporter assays that measure the activation of key cellular stress pathways. These...

  3. ABILITY OF THE MALE RAT PUBERTAL ASSAY TO DETECT ENVIRONMENTAL CHEMICALS THAT ALTER THYROID HORMONE HOMEOSTASIS

    EPA Science Inventory

    ABILITY OF THE MALE RAT PUBERTAL ASSAY TO DETECT ENVIRONMENTAL CHEMICALS THAT ALTER THYROID HORMONE HOMEOSTASIS

    Stoker, Tammy E.1; Laws, Susan C.1; Ferrell, Janet M.1; Cooper, Ralph L.1.

    Endocrinology Branch, RTD, NHEERL, ORD, U.S. EPA, RTP, NC, 27711.

    The...

  4. Methods for the Determination of Chemical Substances in Marine and Estuarine Environmental Matrices - 2nd Edition

    EPA Science Inventory

    This NERL-Cincinnati publication, “Methods for the Determination of Chemical Substances in Marine and Estuarine Environmental Matrices - 2nd Edition” was prepared as the continuation of an initiative to gather together under a single cover a compendium of standardized laborato...

  5. Chemical Transformation System: Cloud Based Cheminformatic Services to Support Integrated Environmental Modeling

    EPA Science Inventory

    Integrated Environmental Modeling (IEM) systems that account for the fate/transport of organics frequently require physicochemical properties as well as transformation products. A myriad of chemical property databases exist but these can be difficult to access and often do not co...

  6. EVALUATING THE ENVIRONMENTAL FRIENDLINESS, ECONOMICS, AND ENERGY EFFICIENCY OF CHEMICAL PROCESSES: HEAT INTEGRATION

    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. In this work diff...

  7. Chemical mixtures and environmental effects: a pilot study to assess ecological exposure and effects in streams

    USGS Publications Warehouse

    Buxton, Herbert T.; Reilly, Timothy J.; Kuivila, Kathryn M.; Kolpin, Dana W.; Bradley, Paul M.; Villeneuve, Daniel L.; Mills, Marc A.

    2015-01-01

    Assessment and management of the risks of exposure to complex chemical mixtures in streams are priorities for human and environmental health organizations around the world. The current lack of information on the composition and variability of environmental mixtures and a limited understanding of their combined effects are fundamental obstacles to timely identification and prevention of adverse human and ecological effects of exposure. This report describes the design of a field-based study of the composition and biological activity of chemical mixtures in U.S. stream waters affected by a wide range of human activities and contaminant sources. The study is a collaborative effort by the U.S. Geological Survey and the U.S. Environmental Protection Agency. Scientists sampled 38 streams spanning 24 States and Puerto Rico. Thirty-four of the sites were located in watersheds impacted by multiple contaminant sources, including industrial and municipal wastewater discharges, crop and animal agricultural runoff, urban runoff, and other point and nonpoint contaminant sources. The remaining four sites were minimally development reference watersheds. All samples underwent comprehensive chemical and biological characterization, including sensitive and specific direct analysis for over 700 dissolved organic and inorganic chemicals and field parameters, identification of unknown contaminants (environmental diagnostics), and a variety of bioassays to evaluate biological activity and toxicity.

  8. Incorporating Chemical Information Instruction and Environmental Science into the First-Year Organic Chemistry Laboratory

    ERIC Educational Resources Information Center

    Landolt, R. G.

    2006-01-01

    The chemical information instruction and environmental science which is incorporated into a first-year organic chemistry laboratory is presented. The students are charged with devised search strategies, conducting online searches and limiting the project scope to ocean systems. The laboratory serves to provide for search strategy development…

  9. STRESS PATHWAY-BASED REPORTER ASSAYS TO ASSESS TOXICITY OF ENVIRONMENTAL CHEMICALS.

    EPA Science Inventory

    There is an increasing need for assays for the rapid and efficient assessment of toxicities of large numbers of environmental chemicals. To meet this need, we are developing cell-based reporter assays that measure the activation of key molecular stress pathways. We are using pro...

  10. Development of an Exchange Format for the European Environmental Chemical Data and Information Network (ECDIN).

    ERIC Educational Resources Information Center

    And Others; Proctor, David, J.

    1978-01-01

    Uses collection and storage of data in an environmental chemicals data bank to develop an exchange format of hierarchical tree structure between network partners. Rules identify and process the nodes in the tree in such a way that information is neither lost nor degraded upon transfer between network partners. (CWM)

  11. Engineering Education: Environmental and Chemical Engineering or Technology Curricula--A European Perspective

    ERIC Educational Resources Information Center

    Glavic, Peter; Lukman, Rebeka; Lozano, Rodrigo

    2009-01-01

    Over recent years, universities have been incorporating sustainable development (SD) into their systems, including their curricula. This article analyses the incorporation of SD into the curricula of chemical and environmental engineering or technology bachelor degrees at universities in the European Union (EU) and European Free Trade Association…

  12. Molecular Modeling for Screening Environmental Chemicals for Estrogenicity: Use of the Toxicant-Target Approach

    EPA Science Inventory

    There is a paucity of relevant experimental information available for the evaluation of the potential health and environmental effects of many man made chemicals. Knowledge of the potential pathways for activity provides a rational basis for the extrapolations inherent in the pre...

  13. Evaluating the involvement of glucocorticoid feedback on the reproductive effects of environmental chemicals

    EPA Science Inventory

    Acute and chronic stressors activate the hypothalamic-pituitary-adrenal (lIPA) axis and are known to suppress reproductive function through central negative feedback of the gonadal axis by glucocorticoids. Recently, several environmental chemicals known to attenuate or suppress t...

  14. Environmental biotechnology: biotechnology solutions for a global environmental problem, hazardous chemical wastes.

    PubMed

    Omenn, G S

    Biotechnology has a growing place in the remediation of hazardous waste sites throughout the world, and especially in Asia where population density is high and land and fresh water are scarce. In-situ bioremediation has been demonstrated already to be highly effective for petroleum hydrocarbons (alkanes, aromatics, polychlorophenols) and organophosphate pesticides in soils and for gasoline by-products (benzene, toluene, xylene) and chlorinated solvents (trichloroethylene) in groundwater. Heavy metals and PCBs are not suitable for bioremediation. Environmental biotechnology includes solid-phase and slurry-phase bioremediation for contaminated soils and site-specific bioreactors for contaminated groundwater. Specific examples are presented. From a policy point of view, accumulated wastes must be detoxified, preferably at sites where they already exist. We cannot continue to rely on their removal and disposal "elsewhere". For current waste streams, we must minimize the volumes and toxicity. Environmental biotechnology will play a key role.

  15. Predicting human intestinal absorption of diverse chemicals using ensemble learning based QSAR modeling approaches.

    PubMed

    Basant, Nikita; Gupta, Shikha; Singh, Kunwar P

    2016-04-01

    Human intestinal absorption (HIA) of the drugs administered through the oral route constitutes an important criterion for the candidate molecules. The computational approach for predicting the HIA of molecules may potentiate the screening of new drugs. In this study, ensemble learning (EL) based qualitative and quantitative structure-activity relationship (SAR) models (gradient boosted tree, GBT and bagged decision tree, BDT) have been established for the binary classification and HIA prediction of the chemicals, using the selected molecular descriptors. The structural diversity of the chemicals and the nonlinear structure in the considered data were tested by the similarity index and Brock-Dechert-Scheinkman statistics. The external predictive power of the developed SAR models was evaluated through the internal and external validation procedures recommended in the literature. All the statistical criteria parameters derived for the performance of the constructed SAR models were above their respective thresholds suggesting for their robustness for future applications. In complete data, the qualitative SAR models rendered classification accuracy of >99%, while the quantitative SAR models yielded correlation (R(2)) of >0.91 between the measured and predicted HIA values. The performances of the EL-based SAR models were also compared with the linear models (linear discriminant analysis, LDA and multiple linear regression, MLR). The GBT and BDT SAR models performed better than the LDA and MLR methods. A comparison of our models with the previously reported QSARs for HIA prediction suggested for their better performance. The results suggest for the appropriateness of the developed SAR models to reliably predict the HIA of structurally diverse chemicals and can serve as useful tools for the initial screening of the molecules in the drug development process.

  16. Role of Environmental Chemicals in Obesity: A Systematic Review on the Current Evidence

    PubMed Central

    Kelishadi, Roya; Poursafa, Parinaz; Jamshidi, Fahimeh

    2013-01-01

    The purpose of this paper is to systematically review the experimental and human studies on obesogenic chemicals and their mechanisms of action to provide a comprehensive view on the multifactorial aspects of obesity. The literatures were searched in available databases. The relevant papers were selected in three phases. After quality assessment, two reviewers extracted the data while another checked their extracted data. In this review, we summarized information regarding environmental chemicals that can be associated with obesity. Most evidence comes from experimental and laboratory studies; however a growing number of human studies also support the role of obesogenic chemicals. The current evidence proposes that the systemic responses to exposure to environmental factors could potentially increase the risk of excess weight. The effects of exposure to these chemicals are of crucial importance during developmental phases of life, when preprogramming for an adipogenic outcome may occur. By considering the adverse transgenerational effects of obesogen chemicals on human health, the global obesity epidemic should be considered as a multifactorial complex disorder necessitating the emphasis of public health interventions for environmental protection. PMID:23840234

  17. Role of environmental chemicals in obesity: a systematic review on the current evidence.

    PubMed

    Kelishadi, Roya; Poursafa, Parinaz; Jamshidi, Fahimeh

    2013-01-01

    The purpose of this paper is to systematically review the experimental and human studies on obesogenic chemicals and their mechanisms of action to provide a comprehensive view on the multifactorial aspects of obesity. The literatures were searched in available databases. The relevant papers were selected in three phases. After quality assessment, two reviewers extracted the data while another checked their extracted data. In this review, we summarized information regarding environmental chemicals that can be associated with obesity. Most evidence comes from experimental and laboratory studies; however a growing number of human studies also support the role of obesogenic chemicals. The current evidence proposes that the systemic responses to exposure to environmental factors could potentially increase the risk of excess weight. The effects of exposure to these chemicals are of crucial importance during developmental phases of life, when preprogramming for an adipogenic outcome may occur. By considering the adverse transgenerational effects of obesogen chemicals on human health, the global obesity epidemic should be considered as a multifactorial complex disorder necessitating the emphasis of public health interventions for environmental protection.

  18. [Predictive models for the assessment of occupational exposure to chemicals: a new challenge for employers].

    PubMed

    Gromiec, Jan Piotr; Kupczewska-Dobecka, Małgorzata; Jankowska, Agnieszka; Czerczak, Sławomir

    2013-01-01

    Employers are obliged to carry out and document the risk associated with the use of chemical substances. The best but the most expensive method is to measure workplace concentrations of chemicals. At present no "measureless" method for risk assessment is available in Poland, but predictive models for such assessments have been developed in some countries. The purpose of this work is to review and evaluate the applicability of selected predictive methods for assessing occupational inhalation exposure and related risk to check the compliance with Occupational Exposure Limits (OELs), as well as the compliance with REACH obligations. Based on the literature data HSE COSHH Essentials, EASE, ECETOC TRA, Stoffenmanager, and EMKG-Expo-Tool were evaluated. The data on validation of predictive models were also examined. It seems that predictive models may be used as a useful method for Tier 1 assessment of occupational exposure by inhalation. Since the levels of exposure are frequently overestimated, they should be considered as "rational worst cases" for selection of proper control measures. Bearing in mind that the number of available exposure scenarios and PROC categories is limited, further validation by field surveys is highly recommended. Predictive models may serve as a good tool for preliminary risk assessment and selection of the most appropriate risk control measures in Polish small and medium size enterprises (SMEs) providing that they are available in the Polish language. This also requires an extensive training of their future users. PMID:24502133

  19. Effect-Based Tools for Monitoring and Predicting the Ecotoxicological Effects of Chemicals in the Aquatic Environment

    PubMed Central

    Connon, Richard E.; Geist, Juergen; Werner, Inge

    2012-01-01

    Ecotoxicology faces the challenge of assessing and predicting the effects of an increasing number of chemical stressors on aquatic species and ecosystems. Herein we review currently applied tools in ecological risk assessment, combining information on exposure with expected biological effects or environmental water quality standards; currently applied effect-based tools are presented based on whether exposure occurs in a controlled laboratory environment or in the field. With increasing ecological relevance the reproducibility, specificity and thus suitability for standardisation of methods tends to diminish. We discuss the use of biomarkers in ecotoxicology including ecotoxicogenomics-based endpoints, which are becoming increasingly important for the detection of sublethal effects. Carefully selected sets of biomarkers allow an assessment of exposure to and effects of toxic chemicals, as well as the health status of organisms and, when combined with chemical analysis, identification of toxicant(s). The promising concept of “adverse outcome pathways (AOP)” links mechanistic responses on the cellular level with whole organism, population, community and potentially ecosystem effects and services. For most toxic mechanisms, however, practical application of AOPs will require more information and the identification of key links between responses, as well as key indicators, at different levels of biological organization, ecosystem functioning and ecosystem services. PMID:23112741

  20. Identification and evaluation of computer models for predicting environmental concentrations of pharmaceuticals and veterinary products in the Nordic environment.

    PubMed

    Wajsman, David; Rudén, Christina

    2006-01-01

    According to European Union Council directive 2001/83, an application for the marketing authorization of a medicinal product shall be accompanied by an environmental risk assessment, including an exposure assessment. Computerized exposure models constitute an important tool in predicting environmental exposure to substances yet to be introduced on the market. This paper reports the process of identifying appropriate exposure models for estimating PECs (Predicted Environmental Concentrations) for pharmaceuticals and veterinary products, focusing on emissions to Swedish aquatic and terrestrial environments via water and sludge from sewage treatment plants. From a large number of information sources, a set of 181 potentially relevant exposure models was identified. A process of scrutinizing and testing these models resulted in a final selection of two models, namely SimpleTreat 3.1 that is used to estimate distribution and elimination of chemicals in sewage treatment plants (resulting in a PEC), and VetPec, suited for veterinary products, that estimates PEC in soil (including pore water), groundwater, and surface water. It is concluded that there is still potential for further development of exposure model(s) specifically designed for pharmaceutical emissions to the Nordic environment and climate. Furthermore, increased regulatory data requirements would facilitate the use of existing models, and improve the quality of the output data from these models. PMID:16030525

  1. The Tox21 robotic platform for the assessment of environmental chemicals--from vision to reality.

    PubMed

    Attene-Ramos, Matias S; Miller, Nicole; Huang, Ruili; Michael, Sam; Itkin, Misha; Kavlock, Robert J; Austin, Christopher P; Shinn, Paul; Simeonov, Anton; Tice, Raymond R; Xia, Menghang

    2013-08-01

    Since its establishment in 2008, the US Tox21 inter-agency collaboration has made great progress in developing and evaluating cellular models for the evaluation of environmental chemicals as a proof of principle. Currently, the program has entered its production phase (Tox21 Phase II) focusing initially on the areas of modulation of nuclear receptors and stress response pathways. During Tox21 Phase II, the set of chemicals to be tested has been expanded to nearly 10,000 (10K) compounds and a fully automated screening platform has been implemented. The Tox21 robotic system combined with informatics efforts is capable of screening and profiling the collection of 10K environmental chemicals in triplicate in a week. In this article, we describe the Tox21 screening process, compound library preparation, data processing, and robotic system validation.

  2. Environmental stability of chemically amplified resists: proposing an industry standard methodology for testing

    NASA Astrophysics Data System (ADS)

    Dean, Kim R.; Kishkovich, Oleg P.

    2000-06-01

    The authors propose the establishment of a new industry standard methodology for testing the environmental stability of chemically amplified chemical resists. Preparatory to making this proposal, they developed a pertinent test apparatus and test procedure that might be used uniformly as an industry-wide best practice. To demonstrate and validate their proposed methodology, the authors subjected two different 193 nm chemically amplified photoresists to test conditions in the 'torture chamber,' simulating actual lithographic environmental scenarios. Depending on the variables of each test run (e.g., different resists, different resist thicknesses, different pollutants, different concentrations, and different humidity levels), a variety of defects were noted and described quantitatively. Of the three contaminants tested, ammonia had the strongest effect. The thin resists were more strongly affected by the contamination.

  3. The Tox21 robotic platform for assessment of environmental chemicals - from vision to reality

    PubMed Central

    Attene-Ramos, Matias S.; Miller, Nicole; Huang, Ruili; Michael, Sam; Itkin, Misha; Kavlock, Robert J.; Austin, Christopher P.; Shinn, Paul; Simeonov, Anton; Tice, Raymond R.; Xia, Menghang

    2013-01-01

    Since its establishment in 2008, the US Tox21 inter-agency collaboration has made great progress in developing and evaluating cellular models for the evaluation of environmental chemicals as a proof of principle. Currently, the program has entered its production phase (Tox21 Phase II) focusing initially on the areas of modulation of nuclear receptors and stress response pathways. During Tox21 Phase II, the set of chemicals to be tested has been expanded to nearly 10,000 (10K) compounds and a fully automated screening platform has been implemented. The Tox21 robotic system combined with informatics efforts is capable of screening and profiling the collection of 10K environmental chemicals in triplicate in a week. In this article, we describe the Tox21 screening process, compound library preparation, data processing, and robotic system validation. PMID:23732176

  4. Predicting Formation Damage in Aquifer Thermal Energy Storage Systems Utilizing a Coupled Hydraulic-Thermal-Chemical Reservoir Model

    NASA Astrophysics Data System (ADS)

    Müller, Daniel; Regenspurg, Simona; Milsch, Harald; Blöcher, Guido; Kranz, Stefan; Saadat, Ali

    2014-05-01

    In aquifer thermal energy storage (ATES) systems, large amounts of energy can be stored by injecting hot water into deep or intermediate aquifers. In a seasonal production-injection cycle, water is circulated through a system comprising the porous aquifer, a production well, a heat exchanger and an injection well. This process involves large temperature and pressure differences, which shift chemical equilibria and introduce or amplify mechanical processes. Rock-fluid interaction such as dissolution and precipitation or migration and deposition of fine particles will affect the hydraulic properties of the porous medium and may lead to irreversible formation damage. In consequence, these processes determine the long-term performance of the ATES system and need to be predicted to ensure the reliability of the system. However, high temperature and pressure gradients and dynamic feedback cycles pose challenges on predicting the influence of the relevant processes. Within this study, a reservoir model comprising a coupled hydraulic-thermal-chemical simulation was developed based on an ATES demonstration project located in the city of Berlin, Germany. The structural model was created with Petrel, based on data available from seismic cross-sections and wellbores. The reservoir simulation was realized by combining the capabilities of multiple simulation tools. For the reactive transport model, COMSOL Multiphysics (hydraulic-thermal) and PHREEQC (chemical) were combined using the novel interface COMSOL_PHREEQC, developed by Wissmeier & Barry (2011). It provides a MATLAB-based coupling interface between both programs. Compared to using COMSOL's built-in reactive transport simulator, PHREEQC additionally calculates adsorption and reaction kinetics and allows the selection of different activity coefficient models in the database. The presented simulation tool will be able to predict the most important aspects of hydraulic, thermal and chemical transport processes relevant to

  5. Environmental impact of industrial sludge stabilization/solidification products: chemical or ecotoxicological hazard evaluation?

    PubMed

    Silva, Marcos A R; Testolin, Renan C; Godinho-Castro, Alcione P; Corrêa, Albertina X R; Radetski, Claudemir M

    2011-09-15

    Nowadays, the classification of industrial solid wastes is not based on risk analysis, thus the aim of this study was to compare the toxicity classifications based on the chemical and ecotoxicological characterization of four industrial sludges submitted to a two-step stabilization/solidification (S/S) processes. To classify S/S products as hazardous or non-hazardous, values cited in Brazilian chemical waste regulations were adopted and compared to the results obtained with a battery of biotests (bacteria, alga and daphnids) which were carried out with soluble and leaching fractions. In some cases the hazardous potential of industrial sludge was underestimated, since the S/S products obtained from the metal-mechanics and automotive sludges were chemically classified as non-hazardous (but non-inert) when the ecotoxicity tests showed toxicity values for leaching and soluble fractions. In other cases, the environmental impact was overestimated, since the S/S products of the textile sludges were chemically classified as non-inert (but non-hazardous) while ecotoxicity tests did not reveal any effects on bacteria, daphnids and algae. From the results of the chemical and ecotoxicological analyses we concluded that: (i) current regulations related to solid waste classification based on leachability and solubility tests do not ensure reliable results with respect to environmental protection; (ii) the two-step process was very effective in terms of metal immobilization, even at higher metal-concentrations. Considering that S/S products will be subject to environmental conditions, it is of great interest to test the ecotoxicity potential of the contaminants release from these products with a view to avoiding environmental impact given the unreliability of ecotoxicological estimations originating from chemical analysis.

  6. An efficient algorithm for de novo predictions of biochemical pathways between chemical compounds

    PubMed Central

    2012-01-01

    Background Prediction of biochemical (metabolic) pathways has a wide range of applications, including the optimization of drug candidates, and the elucidation of toxicity mechanisms. Recently, several methods have been developed for pathway prediction to derive a goal compound from a start compound. However, these methods require high computational costs, and cannot perform comprehensive prediction of novel metabolic pathways. Our aim of this study is to develop a de novo prediction method for reconstructions of metabolic pathways and predictions of unknown biosynthetic pathways in the sense that it does not require any initial network such as KEGG metabolic network to be explored. Results We formulated pathway prediction between a start compound and a goal compound as the shortest path search problem in terms of the number of enzyme reactions applied. We propose an efficient search method based on A* algorithm and heuristic techniques utilizing Linear Programming (LP) solution for estimation of the distance to the goal. First, a chemical compound is represented by a feature vector which counts frequencies of substructure occurrences in the structural formula. Second, an enzyme reaction is represented as an operator vector by detecting the structural changes to compounds before and after the reaction. By defining compound vectors as nodes and operator vectors as edges, prediction of the reaction pathway is reduced to the shortest path search problem in the vector space. In experiments on the DDT degradation pathway, we verify that the shortest paths predicted by our method are biologically correct pathways registered in the KEGG database. The results also demonstrate that the LP heuristics can achieve significant reduction in computation time. Furthermore, we apply our method to a secondary metabolite pathway of plant origin, and successfully find a novel biochemical pathway which cannot be predicted by the existing method. For the reconstruction of a known

  7. Environmental chemical exposures and autism spectrum disorders: a review of the epidemiological evidence.

    PubMed

    Kalkbrenner, Amy E; Schmidt, Rebecca J; Penlesky, Annie C

    2014-11-01

    In the past decade, the number of epidemiological publications addressing environmental chemical exposures and autism has grown tremendously. These studies are important because it is now understood that environmental factors play a larger role in causing autism than previously thought and because they address modifiable risk factors that may open up avenues for the primary prevention of the disability associated with autism. In this review, we covered studies of autism and estimates of exposure to tobacco, air pollutants, volatile organic compounds and solvents, metals (from air, occupation, diet, dental amalgams, and thimerosal-containing vaccines), pesticides, and organic endocrine-disrupting compounds such as flame retardants, non-stick chemicals, phthalates, and bisphenol A. We included studies that had individual-level data on autism, exposure measures pertaining to pregnancy or the 1st year of life, valid comparison groups, control for confounders, and adequate sample sizes. Despite the inherent error in the measurement of many of these environmental exposures, which is likely to attenuate observed associations, some environmental exposures showed associations with autism, especially traffic-related air pollutants, some metals, and several pesticides, with suggestive trends for some volatile organic compounds (e.g., methylene chloride, trichloroethylene, and styrene) and phthalates. Whether any of these play a causal role requires further study. Given the limited scope of these publications, other environmental chemicals cannot be ruled out, but have not yet been adequately studied. Future research that addresses these and additional environmental chemicals, including their most common routes of exposures, with accurate exposure measurement pertaining to several developmental windows, is essential to guide efforts for the prevention of the neurodevelopmental damage that manifests in autism symptoms.

  8. The effects of environmental chemical carcinogens on the microRNA machinery.

    PubMed

    Izzotti, A; Pulliero, A

    2014-07-01

    The first evidence that microRNA expression is early altered by exposure to environmental chemical carcinogens in still healthy organisms was obtained for cigarette smoke. To date, the cumulative experimental data indicate that similar effects are caused by a variety of environmental carcinogens, including polycyclic aromatic hydrocarbons, nitropyrenes, endocrine disruptors, airborne mixtures, carcinogens in food and water, and carcinogenic drugs. Accordingly, the alteration of miRNA expression is a general mechanism that plays an important pathogenic role in linking exposure to environmental toxic agents with their pathological consequences, mainly including cancer development. This review summarizes the existing experimental evidence concerning the effects of chemical carcinogens on the microRNA machinery. For each carcinogen, the specific microRNA alteration signature, as detected in experimental studies, is reported. These data are useful for applying microRNA alterations as early biomarkers of biological effects in healthy organisms exposed to environmental carcinogens. However, microRNA alteration results in carcinogenesis only if accompanied by other molecular damages. As an example, microRNAs altered by chemical carcinogens often inhibits the expression of mutated oncogenes. The long-term exposure to chemical carcinogens causes irreversible suppression of microRNA expression thus allowing the transduction into proteins of mutated oncogenes. This review also analyzes the existing knowledge regarding the mechanisms by which environmental carcinogens alter microRNA expression. The underlying molecular mechanism involves p53-microRNA interconnection, microRNA adduct formation, and alterations of Dicer function. On the whole, reported findings provide evidence that microRNA analysis is a molecular toxicology tool that can elucidate the pathogenic mechanisms activated by environmental carcinogens.

  9. The effects of environmental chemical carcinogens on the microRNA machinery.

    PubMed

    Izzotti, A; Pulliero, A

    2014-07-01

    The first evidence that microRNA expression is early altered by exposure to environmental chemical carcinogens in still healthy organisms was obtained for cigarette smoke. To date, the cumulative experimental data indicate that similar effects are caused by a variety of environmental carcinogens, including polycyclic aromatic hydrocarbons, nitropyrenes, endocrine disruptors, airborne mixtures, carcinogens in food and water, and carcinogenic drugs. Accordingly, the alteration of miRNA expression is a general mechanism that plays an important pathogenic role in linking exposure to environmental toxic agents with their pathological consequences, mainly including cancer development. This review summarizes the existing experimental evidence concerning the effects of chemical carcinogens on the microRNA machinery. For each carcinogen, the specific microRNA alteration signature, as detected in experimental studies, is reported. These data are useful for applying microRNA alterations as early biomarkers of biological effects in healthy organisms exposed to environmental carcinogens. However, microRNA alteration results in carcinogenesis only if accompanied by other molecular damages. As an example, microRNAs altered by chemical carcinogens often inhibits the expression of mutated oncogenes. The long-term exposure to chemical carcinogens causes irreversible suppression of microRNA expression thus allowing the transduction into proteins of mutated oncogenes. This review also analyzes the existing knowledge regarding the mechanisms by which environmental carcinogens alter microRNA expression. The underlying molecular mechanism involves p53-microRNA interconnection, microRNA adduct formation, and alterations of Dicer function. On the whole, reported findings provide evidence that microRNA analysis is a molecular toxicology tool that can elucidate the pathogenic mechanisms activated by environmental carcinogens. PMID:24560354

  10. Environmental chemical exposures and autism spectrum disorders: a review of the epidemiological evidence.

    PubMed

    Kalkbrenner, Amy E; Schmidt, Rebecca J; Penlesky, Annie C

    2014-11-01

    In the past decade, the number of epidemiological publications addressing environmental chemical exposures and autism has grown tremendously. These studies are important because it is now understood that environmental factors play a larger role in causing autism than previously thought and because they address modifiable risk factors that may open up avenues for the primary prevention of the disability associated with autism. In this review, we covered studies of autism and estimates of exposure to tobacco, air pollutants, volatile organic compounds and solvents, metals (from air, occupation, diet, dental amalgams, and thimerosal-containing vaccines), pesticides, and organic endocrine-disrupting compounds such as flame retardants, non-stick chemicals, phthalates, and bisphenol A. We included studies that had individual-level data on autism, exposure measures pertaining to pregnancy or the 1st year of life, valid comparison groups, control for confounders, and adequate sample sizes. Despite the inherent error in the measurement of many of these environmental exposures, which is likely to attenuate observed associations, some environmental exposures showed associations with autism, especially traffic-related air pollutants, some metals, and several pesticides, with suggestive trends for some volatile organic compounds (e.g., methylene chloride, trichloroethylene, and styrene) and phthalates. Whether any of these play a causal role requires further study. Given the limited scope of these publications, other environmental chemicals cannot be ruled out, but have not yet been adequately studied. Future research that addresses these and additional environmental chemicals, including their most common routes of exposures, with accurate exposure measurement pertaining to several developmental windows, is essential to guide efforts for the prevention of the neurodevelopmental damage that manifests in autism symptoms. PMID:25199954

  11. Environmental Chemical Exposures and Autism Spectrum Disorders: A Review of the Epidemiological Evidence

    PubMed Central

    Kalkbrenner, Amy E.; Schmidt, Rebecca J.; Penlesky, Annie C.

    2016-01-01

    In the past decade, the number of epidemiological publications addressing environmental chemical exposures and autism has grown tremendously. These studies are important because it is now understood that environmental factors play a larger role in causing autism than previously thought and because they address modifiable risk factors that may open up avenues for the primary prevention of the disability associated with autism. In this review, we covered studies of autism and estimates of exposure to tobacco, air pollutants, volatile organic compounds and solvents, metals (from air, occupation, diet, dental amalgams, and thimerosal-containing vaccines), pesticides, and organic endocrine-disrupting compounds such as flame retardants, non-stick chemicals, phthalates, and bisphenol A. We included studies that had individual-level data on autism, exposure measures pertaining to pregnancy or the 1st year of life, valid comparison groups, control for confounders, and adequate sample sizes. Despite the inherent error in the measurement of many of these environmental exposures, which is likely to attenuate observed associations, some environmental exposures showed associations with autism, especially traffic-related air pollutants, some metals, and several pesticides, with suggestive trends for some volatile organic compounds (e.g., methylene chloride, trichloroethylene, and styrene) and phthalates. Whether any of these play a causal role requires further study. Given the limited scope of these publications, other environmental chemicals cannot be ruled out, but have not yet been adequately studied. Future research that addresses these and additional environmental chemicals, including their most common routes of exposures, with accurate exposure measurement pertaining to several developmental windows, is essential to guide efforts for the prevention of the neurodevelopmental damage that manifests in autism symptoms. PMID:25199954

  12. Three-dimensional prediction of soil physical, chemical, and hydrological properties in a forested catchment of the Santa Catalina CZO

    NASA Astrophysics Data System (ADS)

    Shepard, C.; Holleran, M.; Lybrand, R. A.; Rasmussen, C.

    2014-12-01

    Understanding critical zone evolution and function requires an accurate assessment of local soil properties. Two-dimensional (2D) digital soil mapping provides a general assessment of soil characteristics across a sampled landscape, but lacks the ability to predict soil properties with depth. The utilization of mass-preserving spline functions enable the extrapolation of soil properties with depth, extending predictive functions to three-dimensions (3D). The present study was completed in the Marshall Gulch (MG) catchment, located in the Santa Catalina Mountains, 30 km northwest of Tucson, Arizona, as part of the Santa Catalina-Jemez Mountains Critical Zone Observatory. Twenty-four soil pits were excavated and described following standard procedures. Mass-preserving splines were used to extrapolate mass carbon (kg C m-2); percent clay, silt, and sand (%); sodium mass flux (kg Na m-2); and pH for 24 sampled soil pits in 1-cm depth increments. Saturated volumetric water content (θs) and volumetric water content at 10 kPa (θ10) were predicted using ROSETTA and established empirical relationships. The described profiles were all sampled to differing depths; to compensate for the unevenness of the profile descriptions, the soil depths were standardized from 0.0 to 1.0 and then split into five equal standard depth sections. A logit-transformation was used to normalize the target variables. Step-wise regressions were calculated using available environmental covariates to predict the properties of each variable across the catchment in each depth section, and interpolated model residuals added back to the predicted layers to generate the final soil maps. Logit-transformed R2 for the predictive functions varied widely, ranging from 0.20 to 0.79, with logit-transformed RMSE ranging from 0.15 to 2.77. The MG catchment was further classified into clusters with similar properties based on the environmental covariates, and representative depth functions for each target variable

  13. Environmental properties and aquatic hazard assessment of anionic surfactants: physico-chemical, environmental fate and ecotoxicity properties.

    PubMed

    Könnecker, Gustav; Regelmann, Jürgen; Belanger, Scott; Gamon, Konrad; Sedlak, Richard

    2011-09-01

    This paper summarizes the environmental hazard assessment of physicochemical properties, environmental fate and behavior and the ecotoxicity of a category of 61 anionic surfactants (ANS), comprised of alkyl sulfates (AS), primary alkane sulfonates (PAS) and alpha-olefin sulfonates (AOS) under the High Production Volume Chemicals Program of the Organisation for Economic Co-operation and Development (OECD). The most important common structural feature of the category members examined here is the presence of a predominantly linear aliphatic hydrocarbon chain with a polar sulfate or sulfonate group, neutralized with a counter-ion. The hydrophobic hydrocarbon chain (with a length between C(8) and C(18)) and the polar sulfate or sulfonate groups confer surfactant properties and enable the commercial use of these substances as anionic surfactants. The close structural similarities lead to physico-chemical properties and environmental fate characteristics which follow a regular pattern and justify the applied read-across within a category approach. Common physical and/or biological properties result in structurally similar breakdown products and are, together with the surfactant properties, responsible for similar environmental behavior. The structural similarities result in the same mode of ecotoxic action. Within each of the three sub-categories of ANS the most important parameter influencing ecotoxicity is the varying length of the alkyl chain. Although the counter-ion may also influence the physico-chemical properties, there is no indication that it significantly affects chemical reactivity, environmental fate and behavior or ecotoxicity of these chemicals. Deduced from physico-chemical and surfactancy properties, the main target compartment for the substances of the ANS category is the hydrosphere. They are quantitatively removed in waste water treatment plants, mainly by biodegradation. Quantitative removal in biological treatment plants is reflected by low AS

  14. Simulating Microdosimetry of Environmental Chemicals for EPA’s Virtual Liver

    EPA Science Inventory

    US EPA Virtual Liver (v-Liver) is a cellular systems model of hepatic tissues aimed at predicting chemical-induced adverse effects through agent-based modeling. A primary objective of the project is to extrapolate in vitro data to in vivo outcomes. Agent-based approaches to tissu...

  15. Predicting aquatic toxicities of chemical pesticides in multiple test species using nonlinear QSTR modeling approaches.

    PubMed

    Basant, Nikita; Gupta, Shikha; Singh, Kunwar P

    2015-11-01

    In this study, we established nonlinear quantitative-structure toxicity relationship (QSTR) models for predicting the toxicities of chemical pesticides in multiple aquatic test species following the OECD (Organization for Economic Cooperation and Development) guidelines. The decision tree forest (DTF) and decision tree boost (DTB) based QSTR models were constructed using a pesticides toxicity dataset in Selenastrum capricornutum and a set of six descriptors. Other six toxicity data sets were used for external validation of the constructed QSTRs. Global QSTR models were also constructed using the combined dataset of all the seven species. The diversity in chemical structures and nonlinearity in the data were evaluated. Model validation was performed deriving several statistical coefficients for the test data and the prediction and generalization abilities of the QSTRs were evaluated. Both the QSTR models identified WPSA1 (weighted charged partial positive surface area) as the most influential descriptor. The DTF and DTB QSTRs performed relatively better than the single decision tree (SDT) and support vector machines (SVM) models used as a benchmark here and yielded R(2) of 0.886 and 0.964 between the measured and predicted toxicity values in the complete dataset (S. capricornutum). The QSTR models applied to six other aquatic species toxicity data yielded R(2) of >0.92 (DTF) and >0.97 (DTB), respectively. The prediction accuracies of the global models were comparable with those of the S. capricornutum models. The results suggest for the appropriateness of the developed QSTR models to reliably predict the aquatic toxicity of chemicals and can be used for regulatory purpose.

  16. Predicting aquatic toxicities of chemical pesticides in multiple test species using nonlinear QSTR modeling approaches.

    PubMed

    Basant, Nikita; Gupta, Shikha; Singh, Kunwar P

    2015-11-01

    In this study, we established nonlinear quantitative-structure toxicity relationship (QSTR) models for predicting the toxicities of chemical pesticides in multiple aquatic test species following the OECD (Organization for Economic Cooperation and Development) guidelines. The decision tree forest (DTF) and decision tree boost (DTB) based QSTR models were constructed using a pesticides toxicity dataset in Selenastrum capricornutum and a set of six descriptors. Other six toxicity data sets were used for external validation of the constructed QSTRs. Global QSTR models were also constructed using the combined dataset of all the seven species. The diversity in chemical structures and nonlinearity in the data were evaluated. Model validation was performed deriving several statistical coefficients for the test data and the prediction and generalization abilities of the QSTRs were evaluated. Both the QSTR models identified WPSA1 (weighted charged partial positive surface area) as the most influential descriptor. The DTF and DTB QSTRs performed relatively better than the single decision tree (SDT) and support vector machines (SVM) models used as a benchmark here and yielded R(2) of 0.886 and 0.964 between the measured and predicted toxicity values in the complete dataset (S. capricornutum). The QSTR models applied to six other aquatic species toxicity data yielded R(2) of >0.92 (DTF) and >0.97 (DTB), respectively. The prediction accuracies of the global models were comparable with those of the S. capricornutum models. The results suggest for the appropriateness of the developed QSTR models to reliably predict the aquatic toxicity of chemicals and can be used for regulatory purpose. PMID:26142614

  17. Molecular modeling for screening environmental chemicals for estrogenicity: use of the toxicant-target approach.

    PubMed

    Rabinowitz, James R; Little, Stephen B; Laws, Susan C; Goldsmith, Michael-Rock

    2009-09-01

    There is a paucity of relevant experimental information available for the evaluation of the potential health and environmental effects of many man made chemicals. Knowledge of the potential pathways for activity provides a rational basis for the extrapolations inherent in the preliminary evaluation of risk and the establishment of priorities for obtaining missing data for environmental chemicals. The differential step in many mechanisms of toxicity may be generalized as the interaction between a small molecule (a potential toxicant) and one or more macromolecular targets. An approach based on computation of the interaction between a potential molecular toxicant and a library of macromolecular targets of toxicity has been proposed for preliminary chemical screening. In the current study, the interaction between a series of environmentally relevant chemicals and models of the rat estrogen receptors (ER) was computed and the results compared to an experimental data set of their relative binding affinities. The experimental data set consists of 281 chemicals, selected from the U.S. EPA's Toxic Substances Control Act (TSCA) inventory, that were initially screened using the rat uterine cytosolic ER-competitive binding assay. Secondary analysis, using Lineweaver-Burk plots and slope replots, was applied to confirm that only 15 of these test chemicals were true competitive inhibitors of ER binding with experimental inhibition constants (K(i)) less than 100 microM. Two different rapid computational docking methods have been applied. Each provides a score that is a surrogate for the strength of the interaction between each ligand-receptor pair. Using the score that indicates the strongest interaction for each pair, without consideration of the geometry of binding between the toxicant and the target, all of the active molecules were discovered in the first 16% of the chemicals. When a filter is applied on the basis of the geometry of a simplified pharmacophore for binding to

  18. Molecular modeling for screening environmental chemicals for estrogenicity: use of the toxicant-target approach.

    PubMed

    Rabinowitz, James R; Little, Stephen B; Laws, Susan C; Goldsmith, Michael-Rock

    2009-09-01

    There is a paucity of relevant experimental information available for the evaluation of the potential health and environmental effects of many man made chemicals. Knowledge of the potential pathways for activity provides a rational basis for the extrapolations inherent in the preliminary evaluation of risk and the establishment of priorities for obtaining missing data for environmental chemicals. The differential step in many mechanisms of toxicity may be generalized as the interaction between a small molecule (a potential toxicant) and one or more macromolecular targets. An approach based on computation of the interaction between a potential molecular toxicant and a library of macromolecular targets of toxicity has been proposed for preliminary chemical screening. In the current study, the interaction between a series of environmentally relevant chemicals and models of the rat estrogen receptors (ER) was computed and the results compared to an experimental data set of their relative binding affinities. The experimental data set consists of 281 chemicals, selected from the U.S. EPA's Toxic Substances Control Act (TSCA) inventory, that were initially screened using the rat uterine cytosolic ER-competitive binding assay. Secondary analysis, using Lineweaver-Burk plots and slope replots, was applied to confirm that only 15 of these test chemicals were true competitive inhibitors of ER binding with experimental inhibition constants (K(i)) less than 100 microM. Two different rapid computational docking methods have been applied. Each provides a score that is a surrogate for the strength of the interaction between each ligand-receptor pair. Using the score that indicates the strongest interaction for each pair, without consideration of the geometry of binding between the toxicant and the target, all of the active molecules were discovered in the first 16% of the chemicals. When a filter is applied on the basis of the geometry of a simplified pharmacophore for binding to

  19. Evaluation of the performance of four chemical transport models in predicting the aerosol chemical composition in Europe in 2005

    NASA Astrophysics Data System (ADS)

    Prank, Marje; Sofiev, Mikhail; Tsyro, Svetlana; Hendriks, Carlijn; Semeena, Valiyaveetil; Vazhappilly Francis, Xavier; Butler, Tim; Denier van der Gon, Hugo; Friedrich, Rainer; Hendricks, Johannes; Kong, Xin; Lawrence, Mark; Righi, Mattia; Samaras, Zissis; Sausen, Robert; Kukkonen, Jaakko; Sokhi, Ranjeet

    2016-05-01

    Four regional chemistry transport models were applied to simulate the concentration and composition of particulate matter (PM) in Europe for 2005 with horizontal resolution ~ 20 km. The modelled concentrations were compared with the measurements of PM chemical composition by the European Monitoring and Evaluation Programme (EMEP) monitoring network. All models systematically underestimated PM10 and PM2.5 by 10-60 %, depending on the model and the season of the year, when the calculated dry PM mass was compared with the measurements. The average water content at laboratory conditions was estimated between 5 and 20 % for PM2.5 and between 10 and 25 % for PM10. For majority of the PM chemical components, the relative underestimation was smaller than it was for total PM, exceptions being the carbonaceous particles and mineral dust. Some species, such as sea salt and NO3-, were overpredicted by the models. There were notable differences between the models' predictions of the seasonal variations of PM, mainly attributable to different treatments or omission of some source categories and aerosol processes. Benzo(a)pyrene concentrations were overestimated by all the models over the whole year. The study stresses the importance of improving the models' skill in simulating mineral dust and carbonaceous compounds, necessity for high-quality emissions from wildland fires, as well as the need for an explicit consideration of aerosol water content in model-measurement comparison.

  20. Prediction of Chemical Carcinogenicity in Rodents from in vitro Genetic Toxicity Assays

    NASA Astrophysics Data System (ADS)

    Tennant, Raymond W.; Margolin, Barry H.; Shelby, Michael D.; Zeiger, Errol; Haseman, Joseph K.; Spalding, Judson; Caspary, William; Resnick, Michael; Stasiewicz, Stanley; Anderson, Beth; Minor, Robert

    1987-05-01

    Four widely used in vitro assays for genetic toxicity were evaluated for their ability to predict the carcinogenicity of selected chemicals in rodents. These assays were mutagenesis in Salmonella and mouse lymphoma cells and chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Seventy-three chemicals recently tested in 2-year carcinogenicity studies conducted by the National Cancer Institute and the National Toxicology Program were used in this evaluation. Test results from the four in vitro assays did not show significant differences in individual concordance with the rodent carcinogenicity results; the concordance of each assay was approximately 60 percent. Within the limits of this study there was no evidence of complementarity among the four assays, and no battery of tests constructed from these assays improved substantially on the overall performance of the Salmonella assay. The in vitro assays which represented a range of three cell types and four end points did show substantial agreement among themselves, indicating that chemicals positive in one in vitro assay tended to be positive in the other in vitro assays. To help put this project into its proper context, we emphasize certain features of the study: 1) Standard protocols were used to mimic the major use of STTs worldwide--screening for mutagens and carcinogens; no attempt was made to optimize protocols for specific chemicals. 2) The 73 NTP chemicals and their 60% incidence of carcinogenicity are probably not representative of the universe of chemicals but rather reflect the recent chemical selection process for the NTP carcinogenicity assay. 3) The small, diverse group of chemicals precludes a meaningful evaluation of the predictive utility of chemical structure information. 4) The NTP is currently testing these same 73 chemicals in two in vivo STTs for chromosomal effects. 5) Complete data for an additional group of 30 to 40 NTP chemicals will be gathered on

  1. Prediction of organ toxicity endpoints by QSAR modeling based on precise chemical-histopathology annotations.

    PubMed

    Myshkin, Eugene; Brennan, Richard; Khasanova, Tatiana; Sitnik, Tatiana; Serebriyskaya, Tatiana; Litvinova, Elena; Guryanov, Alexey; Nikolsky, Yuri; Nikolskaya, Tatiana; Bureeva, Svetlana

    2012-09-01

    The ability to accurately predict the toxicity of drug candidates from their chemical structure is critical for guiding experimental drug discovery toward safer medicines. Under the guidance of the MetaTox consortium (Thomson Reuters, CA, USA), which comprised toxicologists from the pharmaceutical industry and government agencies, we created a comprehensive ontology of toxic pathologies for 19 organs, classifying pathology terms by pathology type and functional organ substructure. By manual annotation of full-text research articles, the ontology was populated with chemical compounds causing specific histopathologies. Annotated compound-toxicity associations defined histologically from rat and mouse experiments were used to build quantitative structure-activity relationship models predicting subcategories of liver and kidney toxicity: liver necrosis, liver relative weight gain, liver lipid accumulation, nephron injury, kidney relative weight gain, and kidney necrosis. All models were validated using two independent test sets and demonstrated overall good performance: initial validation showed 0.80-0.96 sensitivity (correctly predicted toxic compounds) and 0.85-1.00 specificity (correctly predicted non-toxic compounds). Later validation against a test set of compounds newly added to the database in the 2 years following initial model generation showed 75-87% sensitivity and 60-78% specificity. General hepatotoxicity and nephrotoxicity models were less accurate, as expected for more complex endpoints.

  2. Prediction of cancer cell sensitivity to natural products based on genomic and chemical properties.

    PubMed

    Yue, Zhenyu; Zhang, Wenna; Lu, Yongming; Yang, Qiaoyue; Ding, Qiuying; Xia, Junfeng; Chen, Yan

    2015-01-01

    Natural products play a significant role in cancer chemotherapy. They are likely to provide many lead structures, which can be used as templates for the construction of novel drugs with enhanced antitumor activity. Traditional research approaches studied structure-activity relationship of natural products and obtained key structural properties, such as chemical bond or group, with the purpose of ascertaining their effect on a single cell line or a single tissue type. Here, for the first time, we develop a machine learning method to comprehensively predict natural products responses against a panel of cancer cell lines based on both the gene expression and the chemical properties of natural products. The results on two datasets, training set and independent test set, show that this proposed method yields significantly better prediction accuracy. In addition, we also demonstrate the predictive power of our proposed method by modeling the cancer cell sensitivity to two natural products, Curcumin and Resveratrol, which indicate that our method can effectively predict the response of cancer cell lines to these two natural products. Taken together, the method will facilitate the identification of natural products as cancer therapies and the development of precision medicine by linking the features of patient genomes to natural product sensitivity.

  3. Prediction of contaminant persistence in aqueous phase: a quantum chemical approach.

    PubMed

    Blotevogel, Jens; Mayeno, Arthur N; Sale, Tom C; Borch, Thomas

    2011-03-15

    At contaminated field sites where active remediation measures are not feasible, monitored natural attenuation is sometimes the only alternative for surface water or groundwater decontamination. However, due to slow degradation rates of some contaminants under natural conditions, attenuation processes and their performance assessment can take several years to decades to complete. Here, we apply quantum chemical calculations to predict contaminant persistence in the aqueous phase. For the test compound hexamethylphosphoramide (HMPA), P-N bond hydrolysis is the only thermodynamically favorable reaction that may lead to its degradation under reducing conditions. Through calculation of aqueous Gibbs free energies of activation for all potential reaction mechanisms, it is predicted that HMPA hydrolyzes via an acid-catalyzed mechanism at pH < 8.2, and an uncatalyzed mechanism at pH 8.2-8.5. The estimated half-lives of thousands to hundreds of thousands of years over the groundwater-typical pH range of 6.0 to 8.5 indicate that HMPA will be persistent in the absence of suitable oxidants. At pH 0, where the hydrolysis reaction is rapid enough to enable measurement, the experimentally determined rate constant and half-life are in excellent agreement with the predicted values. Since the quantum chemical methodology described herein can be applied to virtually any contaminant or reaction of interest, it is especially valuable for the prediction of persistence when slow reaction rates impede experimental investigations and appropriate QSARs are unavailable.

  4. A two-scale system to identify environmental risk of chemical industry clusters.

    PubMed

    Huang, Lei; Wan, Wenbo; Li, Fengying; Li, Bing; Yang, Jie; Bi, Jun

    2011-02-15

    Recent reform policies in China have spurred rapid industrial development. This has led to a large increase in chemical accidents, which may have catastrophic impacts on the local population and environment. As industrial facilities become more complex, it becomes more difficult to control and mitigate the risks associated with chemical accidents. In this study, we propose a two-scale system for assessing the environmental risk level of chemical industry clusters. A series of risk early warning indices for both the plant-specific level and regional clusters level are used in this system. Firstly, at the enterprise scale, a risk early warning index is constructed using inputs such as the presence of hazardous materials, the operation of critical plant equipment and the efficiency of extant management techniques. Secondly, an index for quantifying risks on regional scales depends on environmental, economic, and social conditions as well as the specific enterprises' components. As an illustration, the system is applied to a case study involving a five-plant chemical industry cluster in Jiangsu province, China. A geographical information system-based methodology is used to obtain a composite index score for each mesh of the five plants. The results prove that the proposed two-scale early warning system can efficiently identify environmental risk and help guide emergency responses at both the enterprise and cluster level.

  5. Governance of complex socio-environmental risks: the case of hazardous chemicals in the Baltic Sea.

    PubMed

    Karlsson, Mikael; Gilek, Michael; Udovyk, Oksana

    2011-03-01

    Complex socio-environmental risks challenge society. In response to scientific uncertainty and sociopolitical controversies, environmental governance, precaution, and the ecosystem approach to management are held forward as complements to governmental risk-based sector-restricted regulation. We analyze this development for hazardous substances in the Baltic Sea. Based on interviews and policy analysis, we study informal governance and, in particular, four central EU and international policies, and investigate how present governance relates to risks and objectives at hand. While showing emergence of broader governance approaches, we conclude that central objectives will not likely be met. Furthermore, we question the quest for broad environmental governance and emphasize the value of command and control regulation, if it implements precaution. These findings contribute to the theorizing on environmental (risk) governance. Finally, we provide some ideas that could help development and implementation of risk policies for hazardous chemicals in the Baltic Sea as well as other complex risks.

  6. Environmental Chemical Assessment in Clinical Practice: Unveiling the Elephant in the Room.

    PubMed

    Bijlsma, Nicole; Cohen, Marc M

    2016-02-01

    A growing body of evidence suggests chemicals present in air, water, soil, food, building materials and household products are toxicants that contribute to the many chronic diseases typically seen in routine medical practice. Yet, despite calls from numerous organisations to provide clinicians with more training and awareness in environmental health, there are multiple barriers to the clinical assessment of toxic environmental exposures. Recent developments in the fields of systems biology, innovative breakthroughs in biomedical research encompassing the "-omics" fields, and advances in mobile sensing, peer-to-peer networks and big data, provide tools that future clinicians can use to assess environmental chemical exposures in their patients. There is also a need for concerted action at all levels, including actions by individual patients, clinicians, medical educators, regulators, government and non-government organisations, corporations and the wider civil society, to understand the "exposome" and minimise the extent of toxic exposures on current and future generations. Clinical environmental chemical risk assessment may provide a bridge between multiple disciplines that uses new technologies to herald in a new era in personalised medicine that unites clinicians, patients and civil society in the quest to understand and master the links between the environment and human health. PMID:26848668

  7. Environmental Chemical Assessment in Clinical Practice: Unveiling the Elephant in the Room.

    PubMed

    Bijlsma, Nicole; Cohen, Marc M

    2016-02-02

    A growing body of evidence suggests chemicals present in air, water, soil, food, building materials and household products are toxicants that contribute to the many chronic diseases typically seen in routine medical practice. Yet, despite calls from numerous organisations to provide clinicians with more training and awareness in environmental health, there are multiple barriers to the clinical assessment of toxic environmental exposures. Recent developments in the fields of systems biology, innovative breakthroughs in biomedical research encompassing the "-omics" fields, and advances in mobile sensing, peer-to-peer networks and big data, provide tools that future clinicians can use to assess environmental chemical exposures in their patients. There is also a need for concerted action at all levels, including actions by individual patients, clinicians, medical educators, regulators, government and non-government organisations, corporations and the wider civil society, to understand the "exposome" and minimise the extent of toxic exposures on current and future generations. Clinical environmental chemical risk assessment may provide a bridge between multiple disciplines that uses new technologies to herald in a new era in personalised medicine that unites clinicians, patients and civil society in the quest to understand and master the links between the environment and human health.

  8. Environmental Chemical Assessment in Clinical Practice: Unveiling the Elephant in the Room

    PubMed Central

    Bijlsma, Nicole; Cohen, Marc M.

    2016-01-01

    A growing body of evidence suggests chemicals present in air, water, soil, food, building materials and household products are toxicants that contribute to the many chronic diseases typically seen in routine medical practice. Yet, despite calls from numerous organisations to provide clinicians with more training and awareness in environmental health, there are multiple barriers to the clinical assessment of toxic environmental exposures. Recent developments in the fields of systems biology, innovative breakthroughs in biomedical research encompassing the “-omics” fields, and advances in mobile sensing, peer-to-peer networks and big data, provide tools that future clinicians can use to assess environmental chemical exposures in their patients. There is also a need for concerted action at all levels, including actions by individual patients, clinicians, medical educators, regulators, government and non-government organisations, corporations and the wider civil society, to understand the “exposome” and minimise the extent of toxic exposures on current and future generations. Clinical environmental chemical risk assessment may provide a bridge between multiple disciplines that uses new technologies to herald in a new era in personalised medicine that unites clinicians, patients and civil society in the quest to understand and master the links between the environment and human health. PMID:26848668

  9. International Federation of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals.

    PubMed

    Di Renzo, Gian Carlo; Conry, Jeanne A; Blake, Jennifer; DeFrancesco, Mark S; DeNicola, Nathaniel; Martin, James N; McCue, Kelly A; Richmond, David; Shah, Abid; Sutton, Patrice; Woodruff, Tracey J; van der Poel, Sheryl Ziemin; Giudice, Linda C

    2015-12-01

    Exposure to toxic environmental chemicals during pregnancy and breastfeeding is ubiquitous and is a threat to healthy human reproduction. There are tens of thousands of chemicals in global commerce, and even small exposures to toxic chemicals during pregnancy can trigger adverse health consequences. Exposure to toxic environmental chemicals and related health outcomes are inequitably distributed within and between countries; universally, the consequences of exposure are disproportionately borne by people with low incomes. Discrimination, other social factors, economic factors, and occupation impact risk of exposure and harm. Documented links between prenatal exposure to environmental chemicals and adverse health outcomes span the life course and include impacts on fertility and pregnancy, neurodevelopment, and cancer. The global health and economic burden related to toxic environmental chemicals is in excess of millions of deaths and billions of dollars every year. On the basis of accumulating robust evidence of exposures and adverse health impacts related to toxic environmental chemicals, the International Federation of Gynecology and Obstetrics (FIGO) joins other leading reproductive health professional societies in calling for timely action to prevent harm. FIGO recommends that reproductive and other health professionals advocate for policies to prevent exposure to toxic environmental chemicals, work to ensure a healthy food system for all, make environmental health part of health care, and champion environmental justice. PMID:26433469

  10. International Federation of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals.

    PubMed

    Di Renzo, Gian Carlo; Conry, Jeanne A; Blake, Jennifer; DeFrancesco, Mark S; DeNicola, Nathaniel; Martin, James N; McCue, Kelly A; Richmond, David; Shah, Abid; Sutton, Patrice; Woodruff, Tracey J; van der Poel, Sheryl Ziemin; Giudice, Linda C

    2015-12-01

    Exposure to toxic environmental chemicals during pregnancy and breastfeeding is ubiquitous and is a threat to healthy human reproduction. There are tens of thousands of chemicals in global commerce, and even small exposures to toxic chemicals during pregnancy can trigger adverse health consequences. Exposure to toxic environmental chemicals and related health outcomes are inequitably distributed within and between countries; universally, the consequences of exposure are disproportionately borne by people with low incomes. Discrimination, other social factors, economic factors, and occupation impact risk of exposure and harm. Documented links between prenatal exposure to environmental chemicals and adverse health outcomes span the life course and include impacts on fertility and pregnancy, neurodevelopment, and cancer. The global health and economic burden related to toxic environmental chemicals is in excess of millions of deaths and billions of dollars every year. On the basis of accumulating robust evidence of exposures and adverse health impacts related to toxic environmental chemicals, the International Federation of Gynecology and Obstetrics (FIGO) joins other leading reproductive health professional societies in calling for timely action to prevent harm. FIGO recommends that reproductive and other health professionals advocate for policies to prevent exposure to toxic environmental chemicals, work to ensure a healthy food system for all, make environmental health part of health care, and champion environmental justice.

  11. Characterizing the Estrogenic Potential of 1060 Environmental Chemicals by Assessing Growth Kinetics in T47D Cells

    EPA Science Inventory

    In order to detect environmental chemicals that pose a risk of endocrine disruption, high-throughput screening (HTS) tests capable of testing thousands of environmental chemicals are needed. Alteration of estrogen signaling has been implicated in a variety of adverse health effec...

  12. Climate-based archetypes for the environmental fate assessment of chemicals.

    PubMed

    Ciuffo, Biagio; Sala, Serenella

    2013-11-15

    Emissions of chemicals have been on the rise for years, and their impacts are greatly influenced by spatial differentiation. Chemicals are usually emitted locally but their impact can be felt both locally and globally, due to their chemical properties and persistence. The variability of environmental parameters in the emission compartment may affect the chemicals' fate and the exposure at different orders of magnitude. The assessment of the environmental fate of chemicals and the inherent spatial differentiation requires the use of multimedia models at various levels of complexity (from a simple box model to complex computational and high-spatial-resolution models). The objective of these models is to support ecological and human health risk assessment, by reducing the uncertainty of chemical impact assessments. The parameterisation of spatially resolved multimedia models is usually based on scenarios of evaluative environments, or on geographical resolutions related to administrative boundaries (e.g. countries/continents) or landscape areas (e.g. watersheds, eco-regions). The choice of the most appropriate scale and scenario is important from a management perspective, as a balance should be reached between a simplified approach and computationally intensive multimedia models. In this paper, which aims to go beyond the more traditional approach based on scale/resolution (cell, country, and basin), we propose and assess climate-based archetypes for the impact assessment of chemicals released in air. We define the archetypes based on the main drivers of spatial variability, which we systematically identify by adopting global sensitivity analysis techniques. A case study that uses the high resolution multimedia model MAPPE (Multimedia Assessment of Pollutant Pathways in the Environment) is presented. Results of the analysis showed that suitable archetypes should be both climate- and chemical-specific, as different chemicals (or groups of them) have different traits

  13. Climate-based archetypes for the environmental fate assessment of chemicals.

    PubMed

    Ciuffo, Biagio; Sala, Serenella

    2013-11-15

    Emissions of chemicals have been on the rise for years, and their impacts are greatly influenced by spatial differentiation. Chemicals are usually emitted locally but their impact can be felt both locally and globally, due to their chemical properties and persistence. The variability of environmental parameters in the emission compartment may affect the chemicals' fate and the exposure at different orders of magnitude. The assessment of the environmental fate of chemicals and the inherent spatial differentiation requires the use of multimedia models at various levels of complexity (from a simple box model to complex computational and high-spatial-resolution models). The objective of these models is to support ecological and human health risk assessment, by reducing the uncertainty of chemical impact assessments. The parameterisation of spatially resolved multimedia models is usually based on scenarios of evaluative environments, or on geographical resolutions related to administrative boundaries (e.g. countries/continents) or landscape areas (e.g. watersheds, eco-regions). The choice of the most appropriate scale and scenario is important from a management perspective, as a balance should be reached between a simplified approach and computationally intensive multimedia models. In this paper, which aims to go beyond the more traditional approach based on scale/resolution (cell, country, and basin), we propose and assess climate-based archetypes for the impact assessment of chemicals released in air. We define the archetypes based on the main drivers of spatial variability, which we systematically identify by adopting global sensitivity analysis techniques. A case study that uses the high resolution multimedia model MAPPE (Multimedia Assessment of Pollutant Pathways in the Environment) is presented. Results of the analysis showed that suitable archetypes should be both climate- and chemical-specific, as different chemicals (or groups of them) have different traits

  14. Studying the time scale dependence of environmental variables predictability using fractal analysis.

    PubMed

    Yuval; Broday, David M

    2010-06-15

    Prediction of meteorological and air quality variables motivates a lot of research in the atmospheric sciences and exposure assessment communities. An interesting related issue regards the relative predictive power that can be expected at different time scales, and whether it vanishes altogether at certain ranges. An improved understanding of our predictive powers enables better environmental management and more efficient decision making processes. Fractal analysis is commonly used to characterize the self-affinity of time series. This work introduces the Continuous Wavelet Transform (CWT) fractal analysis method as a tool for assessing environmental time series predictability. The high temporal scale resolution of the CWT enables detailed information about the Hurst parameter, a common temporal fractality measure, and thus about time scale variations in predictability. We analyzed a few years records of half-hourly air pollution and meteorological time series from which the trivial seasonal and daily cycles were removed. We encountered a general trend of decreasing Hurst values from about 1.4 (good autocorrelation and predictability), in the sub-daily time scale to 0.5 (which implies complete randomness) in the monthly to seasonal scales. The air pollutants predictability follows that of the meteorological variables in the short time scales but is better at longer scales.

  15. Autoantibodies associated with prenatal and childhood exposure to environmental chemicals in Faroese children.

    PubMed

    Osuna, Christa E; Grandjean, Philippe; Weihe, Pál; El-Fawal, Hassan A N

    2014-11-01

    Methylmercury, polychlorinated biphenyls (PCBs), and perfluorinated compounds (PFCs) are ubiquitous and persistent environmental chemicals with known or suspected toxic effects on the nervous system and the immune system. Animal studies have shown that tissue damage can elicit production of autoantibodies. However, it is not known if autoantibodies similarly will be generated and detectable in humans following toxicant exposures. Therefore, we conducted a pilot study to investigate if autoantibodies specific for neural and non-neural antigens could be detected in children at age 7 years who have been exposed to environmental chemicals. Both prenatal and age-7 exposures to mercury, PCBs, and PFCs were measured in 38 children in the Faroe Islands who were exposed to widely different levels of these chemicals due to their seafood-based diet. Concentrations of IgM and IgG autoantibodies specific to both neural (neurofilaments, cholineacetyltransferase, astrocyte glial fibrillary acidic protein, and myelin basic protein) and non-neural (actin, desmin, and keratin) antigens were measured and the associations of these autoantibody concentrations with chemical exposures were assessed using linear regression. Age-7 blood-mercury concentrations were positively associated with titers of multiple neural- and non-neural-specific antibodies, mostly of the IgM isotype. Additionally, prenatal blood-mercury and -PCBs were negatively associated with anti-keratin IgG and prenatal PFOS was negatively associated with anti-actin IgG. These exploratory findings demonstrate that autoantibodies can be detected in the peripheral blood following exposure to environmental chemicals. The unexpected association of exposures with antibodies specific for non-neural antigens suggests that these chemicals may have toxicities that have not yet been recognized.

  16. Novel integrated-optic chemical sensor for environmental monitoring and process control

    NASA Astrophysics Data System (ADS)

    Edwards, John G.

    1995-01-01

    This paper describes an inexpensive point sensor for chemical detection. The sensor is based on a novel integrated optic interferometer that provides a highly stable platform for measuring low concentrations of specific chemicals in gaseous or aqueous environments. Sensing is accomplished by monitoring refractive index changes in a thin-film surface coating, with specificity for a particular chemical achieved by using a surface coating that selectively interacts with that chemical. Multiple surface coatings can be used for simultaneous detection of several chemicals. This approach has a number of key advantages: (1) it is capable of quantifying concentrations down to at least the parts-per-billion level, yet has a broad dynamic range, (2) it is rapid response (environmental interference (e.g.; electromagnetic fields, radiation, corrosive chemicals), (5) it is compact (centimeter dimensions), (6) it requires minimal power (Chemicals investigated to date include ammonia, benzene, toluene, chlorine, chlorine dioxide and hydrogen. Applications range from worksite and workforce monitoring to agricultural and industrial process control.

  17. The chemical defensome: environmental sensing and response genes in the Strongylocentrotus purpuratus genome.

    PubMed

    Goldstone, J V; Hamdoun, A; Cole, B J; Howard-Ashby, M; Nebert, D W; Scally, M; Dean, M; Epel, D; Hahn, M E; Stegeman, J J

    2006-12-01

    Metazoan genomes contain large numbers of genes that participate in responses to environmental stressors. We surveyed the sea urchin Strongylocentrotus purpuratus genome for homologs of gene families thought to protect against chemical stressors; these genes collectively comprise the 'chemical defensome.' Chemical defense genes include cytochromes P450 and other oxidases, various conjugating enzymes, ATP-dependent efflux transporters, oxidative detoxification proteins, and transcription factors that regulate these genes. Together such genes account for more than 400 genes in the sea urchin genome. The transcription factors include homologs of the aryl hydrocarbon receptor, hypoxia-inducible factor, nuclear factor erythroid-derived 2, heat shock factor, and nuclear hormone receptors, which regulate stress-response genes in vertebrates. Some defense gene families, including the ABCC, the UGT, and the CYP families, have undergone expansion in the urchin relative to other deuterostome genomes, whereas the stress sensor gene families do not show such expansion. More than half of the defense genes are expressed during embryonic or larval life stages, indicating their importance during development. This genome-wide survey of chemical defense genes in the sea urchin reveals evolutionary conservation of this network combined with lineage-specific diversification that together suggest the importance of these chemical stress sensing and response mechanisms in early deuterostomes. These results should facilitate future studies on the evolution of chemical defense gene networks and the role of these networks in protecting embryos from chemical stress during development. PMID:17097629

  18. Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

    PubMed Central

    Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

    2015-01-01

    Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using random forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers were 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the sk