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The Chemical Landscape of High Throughput New Approach Methodologies for Exposure
Citation:
Isaacs, K., K. Dionisio, D. Meyer, K. Phillips, G. Ruiz-Mercado, J. Sobus, E. Ulrich, B. Wetmore, AND J. Wambaugh. The Chemical Landscape of High Throughput New Approach Methodologies for Exposure. SOT, Anaheim, CA, March 15 - 19, 2020. https://doi.org/10.23645/epacomptox.22572859
Impact/Purpose:
This abtract the describes an evaluation of the chemical data landscape associated with high-throughput exposure methods. This research product demonstrates that such exposure new approach methodologies have advanced the Agency's ability to assess exposure and risk to thousands to chemicals for the prioritization of chemicals for further study.
Description:
The rapid characterization of risk to humans and ecosystems from commercial chemicals requires information on both hazard and exposure. The U.S. Environmental Protection Agency’s ToxCast program and the interagency Tox21 initiative have screened thousands of chemicals in various high-throughput (HT) assay systems for in vitro bioactivity. EPA’s ExpoCast program is developing complementary HT methods for characterizing the human and ecological exposures necessary to interpret HT hazard data in a real-world risk context. These new approach methodologies (NAMs) for exposure include computational and analytical tools for characterizing multiple components of the complex pathways chemicals take from their source to human and ecological receptors. These pathway components include chemical use, release, transport, toxicokinetics, and ultimately external and internal exposure. Exposure NAMs being developed in ExpoCast include machine learning models that draw inferences from existing data, statistical frameworks that integrate multiple model predictions, and non-targeted analytical screening methods that generate new HT monitoring information. Here, we evaluate the landscape of exposure NAMs in the context of various chemical lists of scientific and regulatory interest, including the ToxCast and Tox21 libraries, Toxic Substances Control Act (TSCA) inventories, and larger libraries of structures recently curated within EPA’s CompTox Chemicals Dashboard. We show that exposure NAMs drastically improve the coverage of the chemical landscape compared to traditional approaches. While existing HT human exposure predictions provide comprehensive coverage of many key inventories, additional work is needed to develop analogous predictions for ecological receptors. A critical bottleneck that should be addressed via future work is the prediction of pathway specific chemical releases, especially ambient releases to the environment. Furthermore, in vitro toxicokinetics information is needed for additional substances to improve chemical space coverage and expand the domain of associated in silico models. The utility of exposure NAMs has been demonstrated in limited case studies on household dust and consumer products, rapidly increasing the number of chemicals identified in these media. The application of exposure NAMs to additional media will be critical for the improving the scope of evaluation datasets for HT exposure predictions.
URLs/Downloads:
DOI: The Chemical Landscape of High Throughput New Approach Methodologies for Exposure
SOT2020-EXPOSURENAMS_03042020_REVISED.PDF (PDF, NA pp, 1528.768 KB, about PDF)