Have animal data been used inappropriately to estimate risks to humans from environmental trichloroethylene?
Trichloroethylene (TCE) is widely viewed as an environmental hazard. Its major metabolite, chloral hydrate, is a currently used medicine. Regulation of TCE is based on a linear extrapolation from effects of high doses in rodents to risks for humans at low doses. However, metabolic, toxicologic, and epidemiologic data on trichloroethylene and chloral hydrate as well as water chlorination studies call this approach into question. The mechanism of carcinogenesis of TCE and chloral hydrate in rodents is nonlinear: very high doses, sufficient to cause cellular necrosis, are necessary. Malignancy arises from repeated cycles of necrosis and regeneration with the ultimate emergence of hyperplasia and then neoplasia. Metabolites of TCE, trichloroacetic acid and dichloroacetic acid, mediate this toxic effect of TCE. These chloroacetic acids also induce similar lesions in rodents given high doses of the medicine, chloral hydrate. Human epidemiologic data show no increase in mortality or malignancy from substantial chronic exposure to trichloroethylene. Chlorination of drinking water produces much higher levels of chloroacetic acids than could be obtained from metabolizing TCE under current regulations. We conclude that the assumptions underlying current regulations are not applicable to TCE. Instead of a straight-line extrapolation model, a threshold model may be more appropriate. The data suggest that it is possible to increase substantially the allowable trichloroethylene in drinking water without increasing health hazards.
Steinberg
A D
AD
MITRE Corporation, McLean, Virginia 22102.
DeSesso
J M
JM
D000818:Animals; D002697:Chloral Hydrate / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D012307:Risk Factors; D014241:Trichloroethylene / Q000633:toxicity*
D004785:Environmental Pollutants; D014241:Trichloroethylene; D002697:Chloral Hydrate