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Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues
FIGURE 3-1 Composite figure of metabolic pathways relevant to renal toxicity demonstrated in mammalian tissue (see text for references). Abbreviations: DCVC, S-(1,2-dichlorovinyl)-L-cysteine; DCVG, S-(1,2-dichlorovinyl)glutathione; DCVT, 1,2-dichlorovinylthiol; GST, glutathions S-transferase; NAcDCVC, N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine; NAT, N-acetyl transferase; TCA, trichloroacetic acid; TCOH, trichloroethanol; THF, tetrahydrofolate.
Elfarra 1991; Park et al. 1992; Lash et al. 1994; Werner et al. 1995a,b, 1996; Birner et al. 1998). Sulfoxidation of haloalkyl cysteine S-conjugates can constitute a toxification independent of β-lyase-mediated bioactivation (Lash et al. 1994; Werner et al. 1995a,b, 1996; Birner et al. 1998). Lash et al. (2000a,b) extensively reviewed biotransformation and bioactivation of trichloroethylene. Since then, there have been additional investigations of the renal metabolism and effects of trichloroethylene, some with a focus on sulfoxidation, as well as the sulfoxidation and toxicity of other haloalkyl nephrotoxicants (see below).
The sulfoxidation and toxicity of trichloroethylene S-conjugates (involving hepatic or kidney microsomal sulfoxidation of cysteine and mercapturic acid conjugates) have been clearly established (Sausen and Elfarra 1991; Lash et al. 1994; Werner et al. 1996; Krause et al. 2003; Lash et al. 2003). The first report of enzymatic trichloroethylene S-conjugate sulfoxidation was by Ripp et al. (1997), who demonstrated rabbit liver microsomal sulfoxidation of S-(1,2-dichlorovinyl)-L-cysteine. Sulfoxidation was cata-