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J Toxicol. 2012;2012:895391. doi: 10.1155/2012/895391. Epub 2012 Jan 19.

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

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  • 1Environmental and Occupational Health Sciences Institute, UMDNJ-RW Johnson Medical School, Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA.

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.

PMID:
22315591
[PubMed]
PMCID:
PMC3270437
Free PMC Article

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