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COMPARISON OF THE USE OF A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL AND A CLASSICAL PHARMACOKINETIC MODEL FOR DIOXIN EXPOSURE ASSESSMENTS
Citation:
EMOND, C., J. E. MICHALEK, L. S. BIRNBAUM, AND M. J. DEVITO. COMPARISON OF THE USE OF A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL AND A CLASSICAL PHARMACOKINETIC MODEL FOR DIOXIN EXPOSURE ASSESSMENTS. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 113(12):1666-1674, (2005).
Impact/Purpose:
To compare a PBPK model that uses a body burden dependent elimination rate with classical PBPK models
Description:
In epidemiological studies, exposure assessments to TCDD, known as a possible human carcinogen, assume mono or biphasic elimination rates. Recent data suggests a dose dependent elimination rate for TCDD. A PBPK model, which uses a body burden dependent elimination rate, was developed to describe the pharmacokinetics of TCDD. Model validation used data from the Ranch Hand cohort, and a clinical report of two women exposed to TCDD. This model suggests that previous exposure assessments may have significantly underestimated peak blood concentrations, resulting in potential exposure misclassifications. Application of a PBPK model may improve the TCDD exposure assessments in epidemiological studies.