Trichloroethylene

Endpoint summary

Additional information

Studies in experimental animals and humans have shown that trichloroethylene is rapidly and extensively absorbed by all routes of exposure. Once absorbed it readily distributes to all compartments within the body. Although trichloroethylene preferentially partitions into fat rich tissues, there is no evidence of prolonged retention at these sites. Trichloroethylene is predominantly cleared from the body by metabolism, accounting for 50 to 99% of the absorbed dose. Studies in humans and a variety of experimental animal species suggest that the metabolic pathways are common to all species. The major metabolic pathway in all species involves the initial conversion of trichloroethylene by cytochrome P450 to a transient epoxide. This epoxide undergoes intramolecular rearrangement to form trichloroacetaldehyde, which in turn is hydrolysed to form chloral hydrate. Chloral hydrate then acts as a substrate for alcohol dehydrogenase and chloral hydrate dehydrogenase to yield trichloroethanol and trichloroacetic acid respectively. A second quantitatively minor pathway involving conjugation with glutathione has also been identified in rats, mice and humans.

Although all species share common metabolic pathways, differences between species and strains have been identified in the saturability of trichloroethylene metabolism. This has been investigated most thoroughly in rats and mice. Whereas the metabolism of trichloroethylene shows little evidence of saturation in B6C3F1 and Swiss-Webster mice at oral doses of up to 2000 mg/kg, there is clear evidence of saturation in all strains of rat following oral doses of 1000 mg/kg. No evidence of saturation for any metabolic pathway has been found in humans although the exposure levels were generally lower than those used in animal studies and thus saturable concentrations may not have been achieved.

Routes of elimination for trichloroethylene are the same in humans and animals and there is no evidence that the route of exposure influences the route of elimination. Most unmetabolised trichloroethylene is exhaled; the percentage which is exhaled increases when metabolism becomes saturated. Other metabolites which have been detected in exhaled air include carbon dioxide, carbon monoxide and a small amount of trichloroethanol. Metabolites of trichloroethylene are predominantly eliminated in the urine with a small proportion eliminated in the bile and faeces. Other routes of elimination have not been investigated.