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20191103 - An Update on Public Tools for Prediction of Endocrine Hazard and Risk (SETAC NA)
Citation:
Friedman, K., J. Wambaugh, R. Judson, AND A. Williams. 20191103 - An Update on Public Tools for Prediction of Endocrine Hazard and Risk (SETAC NA). Society of Environmental Toxicology and Chemistry NA 40th annual meeting, Toronto, Ontario, CANADA, November 03 - 07, 2019. https://doi.org/10.23645/epacomptox.11310467
Impact/Purpose:
Abstract to be submitted for an invited talk at the Endocrine Platform Session at the Society of Environmental Toxicology and Chemistry 40th annual meeting being held November 2019 in Toronto Canada. A workflow for understanding chemical endocrinicity should begin with assessment of available in silico and in vitro data and predictions, integrated consideration of these information, followed by the use of high-throughput toxicokinetic data and models to transform in vitro concentrations to doses that can be compared to the units of exposure for an endocrine bioactivity:exposure ratio (BER). A BER may be a useful metric for prioritization of substances for further evaluation. This presentation provides a brief overview and update on the status of available tools for such a hazard and risk screening workflow.
Description:
Prediction of potential chemical-induced endocrine hazard and/or risk is relevant for chemical safety assessment internationally, and there are a number of publicly available tools for this purpose. A workflow for understanding chemical endocrinicity should begin with assessment of available in silico and in vitro data and predictions, integrated consideration of these information, followed by the use of high-throughput toxicokinetic data and models to transform in vitro concentrations to doses that can be compared to the units of exposure for an endocrine bioactivity:exposure ratio (BER). A BER may be a useful metric for prioritization of substances for further evaluation. This presentation provides a brief overview and update on the status of available tools for such a hazard and risk screening workflow. An initial source of endocrine activity information can be defined using results from quantitative structure activity models including the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP) and the Collaborative Modeling Project for Androgen Receptor Activity (COMPARA); these models provide information for tens of thousands of chemical structures, well beyond the scope of high-throughput screening (HTS) in vitro. HTS data from the ToxCast program have been used to inform models of estrogen and androgen receptor activity and steroidogenesis disruption, and additional HTS assay data are available for thyroid-related bioactivity. HTS bioactivity data and models should be considered in concert with other available information on cytotoxicity, often referred to as the cytotoxicity “burst” threshold that typically aligns with an increase in the number of non-specific assay responses in vitro. For transformation of bioactive in vitro concentrations to external doses for comparison to exposure doses, an R software package that operationalizes high-throughput toxicokinetic modeling using toxicokinetic data from in vivo, in vitro, and/or in silico experiments, HTTK, is available with iterative refinement. Finally, a new meta-model for aggregate population median exposure, ExpoCast Systematic Empirical Evaluation of Models (SEEM3), is now available. Much of this information is already viewable in the CompTox Chemicals Dashboard. Consideration of hazard and exposure predictions as a set enables a state-of-the-science, risk-driven consideration of endocrine activity in a rapid assessment. This abstract does not necessarily reflect U.S. EPA policy.
URLs/Downloads:
DOI: 20191103 - An Update on Public Tools for Prediction of Endocrine Hazard and Risk (SETAC NA)
PAUL-FRIEDMAN_UPDATE_PUBLIC_TOOLS_ENDOCRINE_EVAL_SETAC_NOV2019.PDF (PDF, NA pp, 2391.158 KB, about PDF)