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 

16330344 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16330344  

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