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Absorption, Distribution and Metabolism of 2,3,7,8-Tetrachlorodibenzodioxin (TCDD) in Experimental Animals

  • T. A. Gasiewicz
  • J. R. Olson
  • L. H. Geiger
  • R. A. Neal
Part of the Environmental Science Research book series (ESRH, volume 26)

Abstract

Current understanding of the absorption, distribution, metabolism, and excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in various mammalian species is reviewed. Previous studies on the influence of solvents and adsorbants on dermal and intestinal absorption of TCDD suggest the vehicle for TCDD may be of importance in assessing the relative risk of a given exposure to this compound. In a variety of animal species the liver and adipose tissues appear to be the major storage organs for TCDD. Interspecies differences in TCDD distribution do not appear to be related to species differences in the acute toxic effects of this compound. Following the administration of radiolabeled TCDD, radioactivity appears to be eliminated from most species through a first-order process. However at present no clear relationship exists between the ability of a given species to excrete TCDD and/or its metabolites and the acute lethal toxicity of TCDD in that species. TCDD-derived radioactivity was found to be largely eliminated in the feces. In hamsters and mice urinary elimination was found to be a major route of excretion. High-performance liquid chromatographic (HPLC) analyses of bile and urine from various species show that radioactivity excreted by these routes is mainly associated with metabolites of TCDD. Additional studies utilizing hamster hepatocytes suggest that TCDD is metabolized by the cytochrome P-450-containing monooxygenases. Although the chemical structures of these TCDD metabolites is unknown, additional studies suggest some of these may be glucuronide conjugates.

Keywords

Body Burden Hepatic Microsome Repeated Oral Dose Adipose Tissue Store Hplc Elution Profile 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • T. A. Gasiewicz
    • 1
  • J. R. Olson
    • 2
  • L. H. Geiger
    • 3
  • R. A. Neal
    • 4
  1. 1.Environmental Health Sciences CenterUniversity of Rochester School of MedicineRochesterUSA
  2. 2.Department of Pharmacology and Therapeutics, School of MedicneState University of New YorkRochesterUSA
  3. 3.Center in ToxicologyVanderbilt UniversityNashvilleUSA
  4. 4.Chemical Industry Institute of ToxicologyResearch Triangle ParkUSA

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