Integration of In Vitro Exposure Data into the ECOTOXicology Knowledgebase and Application to Adverse Outcome Pathway Development

Chemical safety evaluations are shifting to incorporate alternative methods (e.g., in vitro and in silico approaches) to meet demand for rapid, efficient chemical hazard assessments for human health and ecological impacts. Historically, toxicity results from in vitro exposures were not candidates for inclusion in the U.S. EPA’s ECOTOXicology Knowledgebase (ECOTOX). ECOTOX is the world’s largest compilation of curated ecotoxicity data for aquatic and terrestrial organisms, providing support for ecological chemical assessments through identification and curation of toxicity results. Presented here is ECOTOX’s recent expansion to incorporate in vitro studies of chemical ecotoxicity using well-established ECOTOX systematic literature review procedures. Since 2017, in vitro ecotoxicity data from over 575 publications were added to the public website (www.epa.gov/ecotox), with cell, tissue, and/or enzyme exposures from 310 species, including fish, amphibians, reptiles, birds, mammals, plants, algae, and invertebrates. Here we summarize in vitro ecotoxicological data available, identify where in vitro data are currently lacking for research and risk assessment, and demonstrate application of ECOTOX in vitro data in adverse outcome pathway development. This in vitro expansion continues and will evolve to support study quality evaluations and validation of new approach methodologies, necessary components for strengthening evidence certainty and furthering application of alternative approaches in regulatory frameworks.