Class-specific chemical categories represent useful concepts which help guide assessors in making risk decisions for a diverse chemical universe. Chemical categories are defined by both structural and bioactivity/molecular property information where structural information can be encoded as structural alerts to identify chemical categories. This concept has been employed by both industry and government agencies. This approach forms the basis for the Organization for Economic and Cooperative Development guidance document on grouping chemicals through the selection of structure and bioactivity/property-based analogues [Guidance on Grouping Chemicals, 2nd edition Series on Testing and Assessment No. 194, 2014]. Under the Toxic Substances Control Act (TSCA), the US EPA consider risks to potentially exposed or susceptible subpopulations when making risk decisions. In recent amendments to TSCA, “[t]he term ‘potentially exposed or susceptible subpopulation’ means a group of individuals within the general population […] who, due to either greater susceptibility or greater exposure, may be at greater risk than the general population of adverse health effects from exposure to a chemical substance or mixture, such as infants, children, pregnant women, workers, or the elderly.” For this particular group, developmental and reproductive toxicity (DART) endpoints pose a challenging concern to address in a risk assessment context due to the lack of test data. There are a number of tools available or in development that might be useful to inform the evaluation of data poor chemicals on DART endpoints. For example, the US EPA GenRA [Shah et al., 2016] and Proctor & Gamble DART [Wu et al., 2014] models can be used to identify potential DART toxicants. However, challenges regarding chemical domains of applicability for modeled structure alerts can also exist and therefore it is necessary to evaluate the performance and relevance of a structural alert or analog system. Our work examines the use of existing substructure fragments and alerts for identifying potential DART toxicants in the TSCA universe of chemicals and their concordance with new alternative methods such as high-throughput in vitro assays (i.e., ToxCastTM). The views of the authors of this abstract are those of the authors and do not represent Agency policy or endorsement. Mention of trade names of commercial products should not be interpreted as an endorsement by the U.S. Environmental Protection Agency.

Identification and analysis of substructure fragments for developmental and reproductive toxicity endpoints within the Toxic Substances Control Act universe of chemicals

253rd National Meeting (2017)

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