1. Disposition and Pharmacokinetics
1. DISPOSITION AND PHARMACOKINETICS The disposition and pharmacokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds have been investigated in several species and under various exposure conditions. Several reviews on this subject focus on TCDD and related halogenated aromatic hydrocarbons (Neal et al., 1982; Gasiewicz et al., 1983a; Olson et al., 1983; Birnbaum, 1985; van den Berg et al., 1994). The relative biological and toxicological potency of TCDD and related compounds depends not only on the affinity of these compounds for the aryl hydrocarbon receptor (AhR), but on the species-, strain-, and congener-specific pharmacokinetics of these compounds (Neal et al., 1982; Gasiewicz et al., 1983a; Olson et al., 1983; Birnbaum, 1985; van den Berg et al., 1994, DeVito and Birnbaum, 1995). 2,3,7,8-TCDD and other similar compounds discussed here are rapidly absorbed into the body and slowly eliminated, making body burden (bioaccumulation) a reliable indicator of time- integrated exposure and absorbed dose. Because of the slow elimination kinetics, it will be shown in this section that lipid or blood concentrations, which are often measured, are in dynamic equilibrium with other tissue compartments in the body, making the overall body burden and tissue disposition relatively easy to estimate. Finally, it will be shown that body burdens can be correlated with adverse health effects (Hardell et al., 1995; Leonards et al., 1995), further leading to the choice of body burden as the optimal indicator of absorbed dose and potential effects. 1.1. ABSORPTION/BIOAVAILABILITY FOLLOWING EXPOSURE Gastrointestinal, dermal, and transpulmonary absorptions represent potential routes for human exposure to this class of persistent environmental contaminants.
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