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  • Review Article
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Exposure forecasting – ExpoCast – for data-poor chemicals in commerce and the environment

Abstract

Estimates of exposure are critical to prioritize and assess chemicals based on risk posed to public health and the environment. The U.S. Environmental Protection Agency (EPA) is responsible for regulating thousands of chemicals in commerce and the environment for which exposure data are limited. Since 2009 the EPA’s ExpoCast (“Exposure Forecasting”) project has sought to develop the data, tools, and evaluation approaches required to generate rapid and scientifically defensible exposure predictions for the full universe of existing and proposed commercial chemicals. This review article aims to summarize issues in exposure science that have been addressed through initiatives affiliated with ExpoCast. ExpoCast research has generally focused on chemical exposure as a statistical systems problem intended to inform thousands of chemicals. The project exists as a companion to EPA’s ToxCast (“Toxicity Forecasting”) project which has used in vitro high-throughput screening technologies to characterize potential hazard posed by thousands of chemicals for which there are limited toxicity data. Rapid prediction of chemical exposures and in vitro-in vivo extrapolation (IVIVE) of ToxCast data allow for prioritization based upon risk of adverse outcomes due to environmental chemical exposure. ExpoCast has developed (1) integrated modeling approaches to reliably predict exposure and IVIVE dose, (2) highly efficient screening tools for chemical prioritization, (3) efficient and affordable tools for generating new exposure and dose data, and (4) easily accessible exposure databases. The development of new exposure models and databases along with the application of technologies like non-targeted analysis and machine learning have transformed exposure science for data-poor chemicals. By developing high-throughput tools for chemical exposure analytics and translating those tools into public health decisions ExpoCast research has served as a crucible for identifying and addressing exposure science knowledge gaps.

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Fig. 1: Timeline of ExpoCast research.

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Acknowledgements

The research described in this manuscript has been reviewed by the Center for Computational Toxicology and Exposure, in the Office of Research and Development of the U.S. EPA and approved for publication. Approval does not signify those contents necessarily reflect the views and policies of the agency, nor does the mention of trade names or commercial products constitute endorsement or recommendation for use. The authors would like to especially thank Dr. Elaine Cohen Hubal, Dr. Kristin Isaacs, and Dr. Peter Egeghy for their leadership, vision, and tremendous impact on the development and success of the ExpoCast Project, as well as acknowledge the contributions of dozens of researchers, funders, and administrative staff within the U.S. EPA and beyond. It has been a great honor to work with all of you. We appreciate Dr. Kristin Isaacs, Dr. Dan Vallero, Dr. Peter Egeghy, and Dr. Michael Devito for providing U.S. EPA internal technical and clearance reviews of this manuscript. This manuscript was supported by the Intramural Research Program of the Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, and the National Institutes of Health (NIH) from the National Institute of Environmental Health Sciences (P42ES031007). Additional support was provided by the Institute for Environmental Health Solutions at the Gillings School of Global Public Health.

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JFW and JER jointly organized, drafted, and revised the manuscript.

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Wambaugh, J.F., Rager, J.E. Exposure forecasting – ExpoCast – for data-poor chemicals in commerce and the environment. J Expo Sci Environ Epidemiol 32, 783–793 (2022). https://doi.org/10.1038/s41370-022-00492-z

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