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197317 
Journal Article 
Comparison of the use of a physiologically based pharmacokinetic model and a classical pharmacokinetic model for dioxin exposure assessments 
Emond, C; Michalek, JE; Birnbaum, LS; DeVito, MJ 
2005 
Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 
113 
12 
1666-1668 
English 
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. 
Body Burden; Cohort Studies; *Environmental Exposure; Epidemiologic Factors; Humans; Military Personnel; *Models, Biological; Tetrachlorodibenzodioxin/blood/*pharmacokinetics; Time Factors 
Body Burden 
Cohort Studies 
Environmental Exposure 
Epidemiologic Factors 
Humans 
Military Personnel 
Models, Biological 
Tetrachlorodibenzodioxin 
Time Factors 
 

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