Bayesian analysis of a lipid-based physiologically based toxicokinetic model for a mixture of PCBs in rats

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. © 2012 alan f. sasso et al.