Bayesian Analysis of a Lipid-Based Physiologically Based Toxicokinetic Model for a Mixture of PCBs in Rats

الملخص EN

A lipid-based physiologically based toxicokinetic (PBTK) model has been developed for a mixture of six polychlorinated biphenyls (PCBs) in rats.

The aim of this study was to apply population Bayesian analysis to a lipid PBTK model, while incorporating an internal exposure-response model linking enzyme induction and metabolic rate.

Lipid-based physiologically based toxicokinetic models are a subset of PBTK models that can simulate concentrations of highly lipophilic compounds in tissue lipids, without the need for partition coefficients.

A hierarchical treatment of population metabolic parameters and a CYP450 induction model were incorporated into the lipid-based PBTK framework, and Markov-Chain Monte Carlo was applied to in vivo data.

A mass balance of CYP1A and CYP2B in the liver was necessary to model PCB metabolism at high doses.

The linked PBTK/induction model remained on a lipid basis and was capable of modeling PCB concentrations in multiple tissues for all dose levels and dose profiles.