Mapping Mechanistic Pathways of Acute Oral Systemic Toxicity Using Chemical Structure and Bioactivity Measurements.

ABSTRACT: Regulatory agencies around the world have committed to reducing or eliminating animal testing for establishing chemical safety. Adverse outcome pathways can facilitate replacement by providing a mechanistic framework for identifying the appropriate non-animal methods and connecting them to apical adverse outcomes. This study separated 11,992 chemicals with curated rat oral acute toxicity information into clusters of structurally similar compounds. Each cluster was then assigned one or more ToxCast/Tox21 assays by looking for the minimum number of assays required to record at least one positive hit call below cytotoxicity for all acutely toxic chemicals in the cluster. When structural information is used to select assays for testing, none of the chemicals required more than four assays and

SUBMITTER: Edwards SW 

PROVIDER: S-EPMC8915918 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature