||Health Effects Research Lab., Research Triangle Park, NC. ;North Carolina Univ. at Chapel Hill. Curriculum in Toxicology. ;ManTech Environmental Technology, Inc., Research Triangle Park, NC. ;National Inst. of Environmental Health Sciences, Research Triangle Park, NC.
The absorption, distribution, metabolism and excretion of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) was studied in male F344 rats. Oral absorption was dose-dependent. Absorption of 1 nmol/kg by both the oral and intratracheal (itr) routes was about 80%, whereas only about 12% was absorbed through the skin. Tissue distribution was dependent on dose, time, and route of exposure. Liver:fat ratios of 3.4, 2.9, 2.0, and 1.5 were observed 3 days after iv, oral, itr. and dermal administration, respectively, of 1 nmol/kg. Liver:fat ratios were 0.2 and 2.6 by 56 days after 1 and 100 nmol/kg iv, respectively. Dose-dependent elimination in urine and feces was observed beginning 3 weeks after iv administration. However, auto-induction of dioxin metabolism did not occur in vivo when evaluated by biliary excretion of (3H)TBDD or (3H)TCDD in pretreated and naive rats. Dose response profiles for TBDD induction of hepatic cytochromes CYP1A1 and CYP1A2 indicated the latter to be a more sensitive response. Finally, comparison of the dose-response behavior for TBDD induction of hepatic CYP1A2 with hepatic concentrations of TBDD suggests that induction of CYP1A2 alone does not account for nonlinearities in dioxin disposition exemplified by dose-related increases in the ratio of dioxin concentrations in live and fat.