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Metabolism The primary metabolic pathway observed is the epoxidation of vinyl chloride (see fig) to chloroethylene oxide (CEO), which can rearrange spontaneously to chloroacetaldehyde (CAA) (Uziel et al, 1992). The main enzymatic pathway for metabolism of vinylchloride requires microsomal mixed function oxidase, oxygen and NADPH are required as cofactors. In addition, CEO can be hydrolyzed by the enzyme epoxide hydrolase to glycolaldehyde. Vinyl chloride may also be oxidized to 2-chloroethanol and then via alcohol dehydrogenase to CAA. CAA can be oxidized by aldehyde dehydrogenase to 2-chloroacetic acid. 2-Chloroacetic acid can also bind to glutathione to form S-carboxymethylglutathione, which can also be formed from S-formylmethylglutathione. CEO and CAA can react with glutathione via glutathione epoxide transferase (or other glutathione transferases) to form S-formylmethylglutathione. Further metabolism (not shown in fig) occurs with conversion of S-formylmethylglutathione to S-Carboxymethylcysteine and S-(2-hydroxyethyl)-cysteine. N-acetylation of S-(2-hydroxyethyl)-cysteine then yields N-acetyl-S-(2-hydroxyethyl)-cysteine, thiodiglycolate is formed from S-carboxymethyl-cysteine by deamination (Whysner et al, 1996).
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