Quantitative Characterization of Population-Wide Tissue- and Metabolite-Specific Variability in Perchloroethylene Toxicokinetics in Male Mice.

ABSTRACT: Quantification of interindividual variability is a continuing challenge in risk assessment, particularly for compounds with complex metabolism and multi-organ toxicity. Toxicokinetic variability for perchloroethylene (perc) was previously characterized across 3 mouse strains and in 1 mouse strain with various degrees of liver steatosis. To further characterize the role of genetic variability in toxicokinetics of perc, we applied Bayesian population physiologically based pharmacokinetic (PBPK) modeling to the data on perc and metabolites in blood/plasma and tissues of male mice from 45 inbred strains from the Collaborative Cross (CC) mouse population. After identifying the most influential PBPK parameters based on global sensitivity analysis, we fit the model with a hierarchical Bayesian po

SUBMITTER: Dalaijamts C 

PROVIDER: S-EPMC8331149 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature