Comparison of the use of a physiologically based pharmacokinetic model and a classical pharmacokinetic model for dioxin exposure assessments.
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.
Emond
Claude
C
National Research Council, National Academy of Sciences, Washington, DC, USA.
Michalek
Joel E
JE
Birnbaum
Linda S
LS
DeVito
Michael J
MJ
D001822:Body Burden; D015331:Cohort Studies; D004781:Environmental Exposure; D015981:Epidemiologic Factors; D006801:Humans; D008889:Military Personnel; D008954:Models, Biological; D000072317:Polychlorinated Dibenzodioxins / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
D000072317:Polychlorinated Dibenzodioxins