Predictive modeling of biological responses in the rat liver using in vitro Tox21 bioactivity: Benefits from high-throughput toxicokinetics.

ABSTRACT: Computational methods are needed to more efficiently leverage data from in vitro cell-based models to predict what occurs within whole body systems after chemical insults. This study set out to test the hypothesis that in vitro high-throughput screening (HTS) data can more effectively predict in vivo biological responses when chemical disposition and toxicokinetic (TK) modeling are employed. In vitro HTS data from the Tox21 consortium were analyzed in concert with chemical disposition modeling to derive nominal, aqueous, and intracellular estimates of concentrations eliciting 50% maximal activity. In vivo biological responses were captured using rat liver transcriptomic data from the DrugMatrix and TG-Gates databases and evaluated for pathway enrichment. In vivo dosing data were translated

SUBMITTER: Ring C 

PROVIDER: S-EPMC8130852 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature