In humans less than 3% of absorbed tetrachloroethylene is metabolised (Ogata et al., 1971; Fernandez et al., 1976; Monster, 1979; Monster et al., 1979). Tetrachloroethylene undergoes mainly oxidative metabolism, but when this becomes saturated, reductive metabolism occurs. Saturation of tetrachloroethylene metabolism has been demonstrated in experimental animals (Ikeda et al., 1972; Pegg et al., 1979; Schumann et al., 1980; Buben and O'Flaherty, 1985) and humans (Fernandez et al., 1976; Monster et al., 1979).

Tetrachloroethylene is oxidised by cytochrome P450 enzymes to the epoxide (tetrachlorooxiram), which spontaneously rearranges to trichloroacetyl chloride (Bonse et al., 1975; Pegg et al., 1979). This is then hydrolysed to trichloroacetic acid which is excreted in the urine (Yllner, 1961; Daniel, 1963). This can be detected days after exposure (Daniel, 1963; Ikeda, 1977; Monster et al., 1979).

In experimental animals, dichloroacetic acid (Yllner, 1961; Dekant et al., 1986), oxalic acid (Yllner, 1961; Daniel, 1963; Pegg et al., 1979; Dekant et al., 1986), oxalylaminoethanol (Dekant et al., 1986) and tetrachloroacetylaminoethanol (Dekant et al., 1986) have also been detected in urine. The latter is formed from trichloroacetyl chloride and its reaction with phosphatidylaminoethanol, whereas oxalylaminoethanol derives from the intermediate dichlorooxalic acid (BUA, 1996). Animals treated with radiolabelled tetrachloroethylene have been found to excrete a small quantity of radioactivity in the faeces (Yllner, 1961; Schumann et al., 1980).

Information on the presence of the metabolite 2,2,2-trichloroethanol is conflicting. It has been detected in humans (Ikeda et al., 1972; Ikeda, 1977; Monster et al., 1983; Gaillard et al., 1995; Birner et al., 1996; Garnier et al., 1996) exposed to tetrachloroethylene but may be due to contamination with trichloroethylene (Skender et al., 1991).

Once the oxidative cytochrome P450 metabolic pathway is saturated, tetrachloroethylene is metabolised via reductive pathways resulting in 1,2,2-trichlorovinylcysteine and 1,2,2-trichlorovinyl-N-acetylcysteine. The former is formed by binding of tetrachloroethylene to glutathione which is transformed through N-acetylation to 1,2,2-trichlorovinyl-N-acetylcysteine. Since this is the stable metabolite, it is excreted in the urine (BUA, 1996) and has been detected in animals (Dekant et al., 1986) and humans (Birner et al., 1996) exposed to tetrachloroethylene. This pathway of glutathione conjugation is less efficient in humans compared to rodents (Birner et al., 1996).

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