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Comparison of the Use of a Physiologically Based Pharmacokinetic Model and a Classical Pharmacokinetic Model for Dioxin Exposure Assessments

By Michalek, Joel E.

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Book Id: WPLBN0000149283
Format Type: PDF eBook
File Size: 0.2 MB
Reproduction Date: 2005

Title: Comparison of the Use of a Physiologically Based Pharmacokinetic Model and a Classical Pharmacokinetic Model for Dioxin Exposure Assessments  
Author: Michalek, Joel E.
Volume:
Language: English
Subject: Government publications, United Nations., United Nations. Office for Disarmament Affairs
Collections: Government Library Collection, Disarmament Documents
Historic
Publication Date:
Publisher: United Nations- Office for Disarmament Affairs (Unoda)

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Michalek, J. E. (n.d.). Comparison of the Use of a Physiologically Based Pharmacokinetic Model and a Classical Pharmacokinetic Model for Dioxin Exposure Assessments. Retrieved from http://www.ebooklibrary.org/


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Government Reference Publication

Excerpt
Excerpt: In epidemiologic studies, exposure assessments of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) assume a fixed elimination rate. Recent data suggest a dose-dependent elimination rate for TCDD. A physiologically based pharmacokinetic (PBPK) model, which uses a body-burden?dependent elimination rate, was developed previously in rodents to describe the pharmacokinetics of TCDD and has been extrapolated to human exposure for this study. Optimizations were performed using data from a random selection of veterans from the Ranch Hand cohort and data from a human volunteer who was exposed to TCDD. Assessment of this PBPK model used additional data from the Ranch Hand cohort and a clinical report of two women exposed to TCDD. This PBPK model suggests that previous exposure assessments may have significantly underestimated peak blood concentrations, resulting in potential exposure misclassifications. Application of a PBPK model that incorporates an inducible elimination of TCDD may improve the exposure assessments in epidemiologic studies of TCDD. Key words: dioxin, epidemiology, PBPK, pharmacokinetic, physiologically based pharmacokinetic model, Ranch Hand, risk assessment. Environ Health Perspect 113:1666?1668 (2005). doi:10.1289/ehp.8016 [25 August 2005].


 

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