Inter-individual variation in chlorpyrifos toxicokinetics characterized by physiologically based kinetic (PBK) and Monte Carlo simulation comparing human liver microsome and Supersome^™ cytochromes P450 (CYP)-specific kinetic data as model input.

ABSTRACT: The present study compares two approaches to evaluate the effects of inter-individual differences in the biotransformation of chlorpyrifos (CPF) on the sensitivity towards in vivo red blood cell (RBC) acetylcholinesterase (AChE) inhibition and to calculate a chemical-specific adjustment factor (CSAF) to account for inter-individual differences in kinetics (HK_AF). These approaches included use of a Supersome^™ cytochromes P450 (CYP)-based and a human liver microsome (HLM)-based physiologically based kinetic (PBK) model, both combined with Monte Carlo simulations. The results revealed that bioactivation of CPF exhibits biphasic kinetics caused by distinct differences in the Km of CYPs involved, which was elucidated by Supersome^™ CYP rather than by HLM. Use of

SUBMITTER: Zhao S 

PROVIDER: S-EPMC9013686 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature