Abstract
When we began our studies about six years ago on the relationship between the metabolism and hepatotoxicity of trichloroethylene, there seemed to be a great deal more to know about its mechanism of metabolism than about its hepatotoxicity. Knowledge about its metabolism began with the detection by Powell in 1945 of an oxidized metabolite of trichloroethylene with three chlorines on one carbon in human urine. On this basis, she suggested that the metabolism of trichloroethylene proceeds via an unstable epoxide intermediate. Subsequently Daniel (1963) demonstrated that the oxidation of trichloroethylene to trichloroethanol and trichloroacetic acid proceeds without loss of labeled chlorine, which supported an epoxidation mechanism of metabolism followed by an intramolecular chlorine shift. Metabolic investigations by Leibman (1965) identified the liver mixed-function oxidases as the enzyme system primarily responsible for the initial oxidation of trichloroethylene. Other enzyme systems, including those in the adjacent cytoplasm, were found to participate in subsequent hydration, oxidation, reduction, and/or conjugation of secondary metabolites (Byington and Leibman, 1965; Muller et al., 1975). Figure 1 summarizes probable and potential pathways of trichloroethylene biotransformation.
Supported by Grant No. ES-02102 from the National Institutes of Health.
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References
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Reynolds, E.S., Moslen, M.T. (1982). Metabolic Activation and Hepatotoxicity of Trichloroethylene. In: Snyder, R., et al. Biological Reactive Intermediates—II. Advances in Experimental Medicine and Biology, vol 136. Springer, New York, NY. https://doi.org/10.1007/978-1-4757-0674-1_51
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