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EFFECTS OF DOSE AND ROUTE OF EXPOSURE ON DIOXIN DISPOSITION
Citation:
Kedderis, L., J. Dilberto, J. Jackson, P. Linko, J. Goldstein, AND L. Birnbaum. EFFECTS OF DOSE AND ROUTE OF EXPOSURE ON DIOXIN DISPOSITION. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-93/024.
Description:
The absorption, distribution, metabolism and excretion of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) was studied in male F344 rats. ral absorption was dose-dependent. bsorption of 1 nmol/kg by both the oral and intratracheal (itr) routes was -80%, whereas only -12% was absorbed through the sidn. issue distribution was dependent on dose, time, and route of exposure. iver: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. iverfat ratios were 0.2 nd 2.6 by 56 days after 1 and 100 nmol/kg iv, respectively. ose-dependent elimination in urine and feces was observed beginning 3 weeks after iv administration. owever, auto-induction of dioxin metabolism did not occur in vivo when evaluated by biliary excretion of [3H]TBDD or [3HITCDD in pretreated and naive rats. ose-response profiles for TBDD induction of hepatic cytochromes P45OIAl and P45OIA2 indicated the latter to be a more sensitive response. inally, comparison of the dose-response behavior for TBDD induction of hepatic P45OIA2 with hepatic concentrations of TBDD suggests that induction of P45OIA2 alone does not account for nonlinearities in dioxin disposition exemplified by dose-related increases in the ratio of dioxin concentrations in liver and fat.