Knowledge of the metabolism and disposition of a xenobiotic is often critical to an appreciation of the toxic effect(s) of the compound. Further, the fidelity of extrapolation of results from animal testing to possible human health effects is greatly enhanced by the knowledge of metabolic pathways. Investigation of the mechanistic aspects of metabolic processes 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. As part of a continuing effort to study xenobiotic metabolism, this group has investigated the metabolism of 1,2,3-trichloropropane, furan and tetrachlorodibenzofuran. The metabolism and disposition of 14C-1,2,3-trichloropropane have been investigated in male and female rats. The highest concentrations of radioactivity are found in liver, forestomach and kidney after 24 hr. Two urinary metabolites, both from the mercapturic acid pathway, have been identified. The chemical reactivity of butenedialdehyde, the suspected reactive intermediate from furan metabolism, is being investigated. Reaction of the dialdehyde with cysteine-containing compounds results in formation of substituted furans. Evidence for this reaction sequence occurring in vivo is being investigated. The structure of the metabolites of TCDF, a highly toxic contaminant often found in PCB's, continues to be under investigation. Two possible metabolites which have hydroxyl groups in place of chlorines have been synthesized recently. The presence of these compounds in bile of rats treated with TCDF is under investigation.
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