Knowledge of the metabolism and disposition of a xenobiotic is often critical in understanding the toxic effect of the compound. The fidelity of extrapolation of results from animal testing to possible human health effects is also greatly enhanced when metabolic pathways are known. Investigation of the mechanistic aspects of metabolic pathways allows greater understanding of how metabolism of a xenobiotic might lead either to detoxification or to a reactive species with greater toxicity. As more is learned about mechanisms of metabolism more accurate prediction of the possible metabolic pathways for new compounds should be possible. The disposition and metabolism of furan, a hepatotoxic heterocyclic compound, is being studied in male F344 rats. Following an oral dose of 14C-furan, tissue concentration of radioactivity was highest in liver at 24 hr; the next highest tissue level was found in kidney. The structure of the metabolites of TCDF, a highly toxic contaminant often found in PCB's, is under investigation. One metabolite, a hydroxylated tetrachloro compound, has been identified using GC-MS and chemical synthesis. An investigation of the metabolism of dimethylvinyl chloride indicated that the apparent specificity for metabolic oxidation of the methyl group trans to the chlorine is not the result of a regiospecific oxidation. The all trans configuration of the isolated urinary metabolites seems to arise from a subsequent reaction which gives trans product regardless of the stereochemistry of the reactant.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021075-05
Application #
3941484
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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