Incorporation of the glutathione conjugation pathway in an updated physiologically-based pharmacokinetic model for perchloroethylene in mice.

ABSTRACT:

Background

Perchloroethylene (perc) induced target organ toxicity has been associated with tissue-specific metabolic pathways. Previous physiologically-based pharmacokinetic (PBPK) modeling of perc accurately predicted oxidative metabolites but suggested the need to better characterize glutathione (GSH) conjugation as well as toxicokinetic uncertainty and variability.

Objectives

We updated the previously published "harmonized" perc PBPK model in mice to better characterize GSH conjugation metabolism as well as the uncertainty and variability of perc toxicokinetics.

Methods

The updated PBPK model includes expanded models for perc and its oxidative metabolite trichloroacetic acid (TCA), and physiologically-based sub-models for conjugative metabolites. Previously compile

SUBMITTER: Dalaijamts C 

PROVIDER: S-EPMC6051410 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature