Toxicokinetic Modeling as a Tool for Risk Estimation: 2,3,7,8-Tetrachlorodibenzo-P-Dioxin

Abstract

Concepts of toxicokinetic modeling and the relevance of toxicokinetics for understanding dose-response relationships, species scaling, and risk estimation are broached. A physiological one-compartment model for 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD) is presented in detail. It describes the TCDD burden of the human body, which results from TCDD-contaminated food, in dependence of age. The model was validated using a series of measured values obtained by other authors and this group. They represent lipid-based concentrations of TCDD in liver, blood, adipose tissue, feces, and mother's milk in dependence of age. Special attention was paid to the TCDD burden in infants resulting from feeding with mother's milk or formula. Model simulations demonstrate that TCDD burden can amount to 10 mg/kg of lipids after nursing for 6 months with mother's milk exclusively This is still within the range of the concentrations found in adults. After the nursing period, TCDD burden declines. From the age of 7 years on, there is no longer a difference in the TCDD burden, independently of the food they had received as infants. According to the model, elimination half-life of TCDD from the body is not constant but increases during life starting from a few months in newborns to several years in adults.