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

Alan F. Sasso, Panos G. Georgopoulos, Sastry S. Isukapalli, Kannan Krishnan

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number895391
JournalJournal of Toxicology
Volume2012
DOIs
StatePublished - 2012

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

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