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Journal of Toxicology
Volume 2012 (2012), Article ID 895391, 10 pages
http://dx.doi.org/10.1155/2012/895391
Research Article

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

1Environmental and Occupational Health Sciences Institute, UMDNJ-RW Johnson Medical School, Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA
2Department of Chemical and Biochemical Engineering, Rutgers University, 98 Brett Road, Piscataway, NJ 08854, USA
3Département de Santé Environnementale et Santé au Travail, 2375 Cote-Sainte-Catherine, Université de Montréal, Montreal, Road QC, Canada H3C 3J7

Received 12 August 2011; Revised 5 October 2011; Accepted 6 October 2011

Academic Editor: Jane C. Caldwell

Copyright © 2012 Alan F. Sasso et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.