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Bayesian analysis of a lipid-based physiologically based toxicokinetic model for a mixture of PCBs in rats
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نویسنده
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sasso a.f. ,georgopoulos p.g. ,isukapalli s.s. ,krishnan k.
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منبع
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journal of toxicology - 2012 - دوره : 2012 - شماره : 0
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چکیده
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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.
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آدرس
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environmental and occupational health sciences institute,umdnj-rw johnson medical school,rutgers university,170 frelinghuysen road,piscataway,nj 08854,united states,department of chemical and biochemical engineering,rutgers university,98 brett road,piscataway, United States, environmental and occupational health sciences institute,umdnj-rw johnson medical school,rutgers university,170 frelinghuysen road,piscataway, United States, environmental and occupational health sciences institute,umdnj-rw johnson medical school,rutgers university,170 frelinghuysen road,piscataway, United States, département de santé environnementale et santé au travail,université de montréal,2375 cote-sainte-catherine,montreal, Canada
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Authors
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