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EFFECT OF PRETREATMENT ON THE BILIARY EXCRETION OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD), 2,3,7,8-TETRACHLORODIBENZOFURAN (TCDF) NAD 3,3'4,4'-TETRACHLOROBIPHENYL (TCB) IN THE RAT
Citation:
McKinley, M., L. Kedderis, AND L. Birnbaum. EFFECT OF PRETREATMENT ON THE BILIARY EXCRETION OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD), 2,3,7,8-TETRACHLORODIBENZOFURAN (TCDF) NAD 3,3'4,4'-TETRACHLOROBIPHENYL (TCB) IN THE RAT. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/073 (NTIS PB94141413).
Description:
The laterally halogenated chemicals 2,3,7,8-tetrachlorodibenzofuran (TCDF) and 3,3',4,4 1-tetrachlorobiphenyl (TCB) exhibit the same spectrum of toxic effects as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prototype and most toxic member of the halogenated aromatic hydrocarbon family. etabolism of all three compounds appears to be the rate-limiting step for excretion, which is primarily via the bile into the feces. herefore, the biliary elimination of TCDF, TCDD, and TCB was examined as an indirect measure of metabolism. ale F344 rats were anesthetized with pentobarbital, the bile duct was cannulated, and 0.1umol[3H]TCDD, [14C]TCDF, or [14C]TCB per kilogram body weight w4s administered iv. ile was collected for 0-8 hours while the animals were kept under anesthesia. o determine if TCDF was able to induce its own metabolism - in vivo, a single dose of 1.0pmol TCDF/kg was administered to rats by oral gavage 3 days prior to iv injection of 0.1 or 0.34mol [14C]TCDF/kg. iliary excretion and hepatic concentrations of [14C]TCDF were significantly increased in the pretreated animals. hese results suggest an auto-induction of TCDF metabolism. ssentially all biliary [14C]TCDF radioactivity was attributable to metabolites.