In humans, only 1% to 3% of the absorbed tetrachloroethylene is metabolized in the liver to trichloroacetic acid, which is then excreted in the urine. Small amounts of trichloroethanol have also been detected in the urine of workers exposed to tetrachloroethylene. The rate of urinary elimination is slower than the rate for exhalation.
Studies of dry-cleaning shop workers have shown that urinary metabolite levels increase linearly with air concentrations of up to 100 ppm tetrachloroethylene, then level off at higher concentrations. This indicates the saturability of the tetrachloroethylene metabolic pathways (Agency for Toxic Substances and Disease Registry 1997).
Metabolism of tetrachloroethylene occurs by cytochrome P450-dependent oxidation and glutathione conjugation. The cytochrome P450 pathway generates tri- and dichloroacetate as metabolites of tetrachloroethylene, and these are associated with hepatic toxicity and carcinogenicity. Glutathione conjugation pathway leads to selective formation of reactive metabolites in the kidneys. It is associated with tetrachloroethylene-induced renal toxicity and carcinogenicity (Lash and Parker 2001). |