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RECORD NUMBER: 14 OF 35

OLS Field Name OLS Field Data
Main Title Disposition of 2,3,7,8-Tetrabromodibenzo-p-Dioxin and 2,3,7,8-Tetrachlorodibenzo-p-dioxin in the Rat: Biliary Excretion and Induction of Cytochromes CYP1A1 and CYP1A2.
Author Kedderis, L. B. ; Diliberto, J. J. ; Linko, P. ; Goldstein, J. A. ; Birnbaum, L. S. ;
CORP Author Health Effects Research Lab., Research Triangle Park, NC. Environmental Toxicology Div. ;North Carolina Univ. at Chapel Hill. ;National Inst. of Environmental Health Sciences, Research Triangle Park, NC.
Publisher c1992
Year Published 1992
Report Number EPA/600/J-92/060;
Stock Number PB92-150747
Additional Subjects Pharmacokinetics ; Bile ; Enzyme induction ; Cytochromes ; Tetrachlorodibenzodioxin ; Toxicology ; Feces ; Liquid chromatography ; Radioimmunoassay ; Rats ; Dose-response relationships ; Liver ; Adipose tissue ; Reprints ; Tetrabromodibenzodioxins
Holdings
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Status
NTIS  PB92-150747 Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy. NTIS 08/28/1992
Collation 12p
Abstract
The biologic activity and pharmacokinetic properties of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) are similar to those of the chlorinated congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Metabolism of both compounds appears to be rate-limiting for excretion, which is primarily via the feces. Therefore, the biliary elimination of TBDD and TCDD was examined as an indirect assessment of metabolism. Male F344 rats were anesthetized with pentobarbital, and 1 nmol/kg (3H)TBDD or (3H)TCDD was administered iv. Bile was collected for up to 8 hr while rats were maintained under anesthesia. In a second set of studies, the dose-response profiles for induction of cytochromes CYP1A1 and CYP1A2 by TBDD were characterized. The ED50 value for CYP1A1 induction (measured by ethoxyresorufin O-deethylase activity and radioimmunoassay (RIA)) was estimated to be 0.8-1.0 nmol/kg, similar to what has been reported for TCDD. Induction of CYP1A2 (RIA) by TBDD appeared to be a more sensitive response over the dose range studied. Finally, comparison of hepatic CYP1A2 induction vs hepatic concentrations of TBDD 3 days following treatment with 10 vs 1 nmol/kg TBDD suggested that induction of CYP1A2 alone may not account for nonlinearities in dioxin disposition exemplified by dose-related increases in the ratio of dioxin concentrations in liver and adipose tissue.