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- Title
Comparison of the Use of a Physiologically Based Pharmacokinetic Model and a Classical Pharmacokinetic Model for Dioxin Exposure Assessments.
- Authors
Emond, Claude; Michalek, Joel E.; Birnbaum, Linda S.; DeVito, Michael J.
- Abstract
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.
- Subjects
DIOXINS; TETRACHLORODIBENZODIOXIN; POLYCHLORINATED dibenzodioxins; AGRICULTURAL chemicals; AGRICULTURE; PHARMACOKINETICS; CHEMICAL kinetics; PHARMACOLOGY; COHORT analysis
- Publication
Environmental Health Perspectives, 2005, Vol 113, Issue 12, p1666
- ISSN
0091-6765
- Publication type
Article
- DOI
10.1289/ehp.8016