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RECORD NUMBER: 7 OF 10

Main Title Effects of Dose and Route of Exposure on Dioxin Disposition.
Author Kedderis, L. B. ; Diliberto, J. J. ; Jackson, J. A. ; Linko, P. ; Goldstein, J. A. ;
CORP Author 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.
Publisher 1992
Year Published 1992
Report Number EPA/600/J-94/024;
Stock Number PB94-137304
Additional Subjects Environmental exposure pathways ; Dose-response relationships ; Tetrachlorodibenzodioxin ; Pharmacokinetics ; Tissue distribution ; Cytochromes ; Liver ; Enzyme induction ; Reprints ; Tetrabromodibenzodioxins
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NTIS  PB94-137304 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 6p
Abstract
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.