Screening industrial chemicals for human developmental toxicity in the DevTox Germ Layer Reporter platform

The EPA New Chemicals Collaborative Research Program (NCCRP) seeks to maximize the efficiency and robustness of the new chemical review process under the Toxic Substances Control Act (TSCA) using new approach methods (NAMs) that represent the best available science. Consideration of the possible health hazards to pregnant women, and their developing offspring, for new chemical submissions is challenged by an insufficient number of acceptable screening modalities to quickly identify potential hazards to humans. The DevTox Germ Layer Reporter (GLR) assay platform evaluates chemical effects on early germ layer development and has been demonstrated to be a viable option for rapid chemical screening. The objective of this study was to screen a structurally diverse set of 171 representative chemicals selected from the TSCA non-confidential active inventory, and 54 in vitro assay reference chemicals, for potential developmental toxicity in the DevTox GLR-Endo assay. Assay performance metrics, as well as predictivity across a set of 16 reference developmental toxicants, were consistent with prior reporting and within acceptable parameters. Of the 38 reference chemicals not previously evaluated in the assay, 25 were identified as active, with 13 demonstrating selectivity for the SOX17 assay endpoint. For the test chemical set, 60 of the 165 chemicals analyzed were active, with 29 exhibiting a degree of selective activity. The results provide coverage of a critical toxicological domain for a set of chemicals relevant to the development of NAM-based methods for the NCCRP and may inform the development of tools in a NAMs-based hazard assessment strategy.