Use of IVIVE and Data from a Stem Cell-based Assay to Predict Developmental Toxicity Potential

To support implementation of NAMs for regulatory decision-making on developmental toxicity, FDA and NIEHS scientists and collaborators evaluated the performance of the devTOX quickPredict assay for predicting lowest effect levels in rat developmental toxicity studies. Studies conducted during 2020 and 2021 focused on developmental toxicity potential of valproic acid and analogues (Chang et al. 2022) and 186 chemicals from the Tox21 program. Developmental toxicity potential (dTP) concentrations from the devTOX quickPredict assay were used as inputs to IVIVE analyses to estimate equivalent administered doses that would result in the maximum plasma concentrations equivalent to dTP concentrations. Results suggested that the devTOX quickPredict assay can quantitatively predict developmental toxicity potential at concentrations relevant to human exposure and in some cases may provide a more conservative hazard estimate than animal studies for use in risk assessment.