Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) are toxic environmental and industrial contaminants. Dermal absorption constitutes a major route of exposure to these chemicals with maximal absorption of a low dose ranging from 40% (TCDD) to 65% (TCDF). Absorption through the skin occurs very slowly yet appears to be more rapid during the first 24 to 48 hours after contact. Our results with TCDD and TCDF suggest that physicochemical properties may govern the rate of absorption of these chemicals. Absorption of a low dose of TCDD through the skin of very young animals is increased compared to absorption through the skin of adult animals. Our results suggest that the potential for systemic exposure might be less in adults compared to children. Polybrominated dibenzo-p-dioxins (PBDDs) and dibenzofurans (PCDFs) are potential environmental contaminants due to their formation from thermolysis or pyrolysis of certain brominated flame retardants. The disposition of TBDD was studied in male F-344 rats following oral or intravenous administration. TBDD exhibited non-linear absorption kinetics with maximal oral absorption (about 80%) occurring at doses <0.01 umol/kg. Distribution to the liver and adipose, the major tissue depots, was dose- dependent, with preferential accumulation in the liver versus the adipose at higher doses. Feces was the major route of elimination and excretion was dose-dependent. The apparent terminal whole body half-life of TBDD was estimated to be 18 days. Within 6 hours, about 6% of the dose was excreted into the bile in metabolized form; pretreatment did not appear to enhance biliary excretion. The overall disposition of TBDD appears similar to that observed for TCDD. The dose-dependent tissue distribution and excretion kinetics suggest important considerations for high to low dose extrapolations.
