Survey of ecotoxicologically-relevant reproductive endpoint coverage within the ECOTOX database across ToxCast ER agonists (ASCCT)

The U.S. EPA’s Endocrine Disruptor Screening Program (EDSP) has been charged with screening thousands of chemicals for their potential to affect the endocrine systems of humans and wildlife. In vitro high throughput screening (HTS) assays have been proposed as a way to prioritize chemicals for EDSP Tier 1 screening. There are 18 HTS assays within ToxCast that measure chemical bioactivity at different sites along the estrogen receptor pathway. Recent work has correlated these in vitro results to in vivo estrogenic endpoints, including the rodent uterotrophic assay. It is unclear how the in vitro HTS assays, generated in mammalian cell-lines and using mammalian receptors, may correlate to in vivo effects in environmentally relevant species, like fish. Here, the availability of ecotoxicological reproduction data and its correlation to in vitro HTS results will be explored. The U.S. EPA’s Ecotox database is a comprehensive knowledgebase for environmental toxicity data. To date, this database contains over 780,000 entries representing ~11,000 chemicals, ~11,700 species, and ~3300 endpoints. A total of 91 chemicals were selected as in vitro estrogen receptor agonists based on the ToxCast ER Model. Of these 91 chemicals, 67 had data within the Ecotox database. Endpoints are plausibly linked to estrogen-disruption were identified including: vitellogenin synthesis, abnormal sexual development, imposex/intersex conditions, effects in progeny counts, and alterations in population sex ratios. This represents a valuable resource for the modeling community. Study coverage will be discussed, and modeling opportunities will be highlighted.This abstract does not necessarily represent U.S. EPA policy.