TR 060 – Trichloroethylene: Assessment of Human Carcinogenic Hazard

Abstract

TR 060 : Trichloroethylene: Assessment of Human Carcinogenic Hazard | May 1994

Trichloroethylene (TCE) has been manufactured on an industrial scale since the beginning of this century and it is used for many different purposes.

The potential carcinogenic effect of occupational exposure to TCE has been the subject of a number of epidemiological studies conducted during 1978-1990, including 4 cohort studies, 2 cancer case-studies without control, one small cohort study without control and one colon cancer case-control study. Each of the above studies has some shortcomings, e.g. flawed study design or small study size. None of the studies demonstrate a link between exposure to TCE and an increase in cancer mortality or excess incidence of liver and colon cancer.

More recently 2 well-designed and well-conducted studies were published. The first, from the US National Cancer Institute studied mortality in a cohort of 6,929 workers with a follow-up of up to 30 years. This study included an extensive exposure assessment which indicated high exposures, in particular during the first part of the study period. The second reported mortality as well as morbidity in an extension of the initial cohort to 1,670 workers, with a follow-up period of 37 years. Both studies showed no association between exposure to TCE and cancer in general or any specific cancer.

Taken together, five cohort studies report on 18,183 workers with a follow-up period of more than 25 years for 4 out of five studies. None of these studies demonstrate a link between exposure to TCE and an increased risk for cancer in general or for any specific type of cancer in man.

These important findings contrast with the results from animal studies where evidence of carcinogenicity has been demonstrated. The principal tumour sites in the mouse are the liver and the lung (separate studies) and in the male rat, the kidney. The occurrence of an increased incidence of mouse liver tumours (hepatocellular carcinomas and adenomas) is the most frequently reported and significant observation in lifetime cancer bioassays of TCE following exposure by either inhalation or gavage. Increased incidences of lung tumours (adenocarcinomas) have been observed in female mice only.

Small increased incidences of kidney carcinomas were found in male Sprague-Dawley, F344 and Osborne-Mendel rats but not in female rats or in any of the other strains tested (ACI, August, Marshall and Wistar) although almost all rats exposed to high TCE levels had tubular cell cytokariomegaly. The carcinogenicity results may have been confounded by the reduced survival due to the nephrotoxic effect of excessive doses of TCE.

A substantial number of biochemical studies have identified mechanisms for the development of the rodent tumours which do not require a direct interaction between TCE or its metabolites and DNA. In each case the mechanism is thought to be linked to species specific metabolism of TCE and to a range of biochemical responses which are either specific to rodents or are not seen at dose levels relevant to human exposure. The excess tumour incidences in the liver, lung or kidney in either mice or rats exposed to TCE are, therefore, considered to be of no real relevance to human carcinogenic hazard.

The rnutagenic potential of TCE has been studied widely in in vitro and in vivo test systems. In many of the reported studies the purity of the test sample is not stated, although potentially mutagenic epoxide stabilisers were almost certainly present. Overall there is no convincing or conclusive evidence that pure TCE is genotoxic.

Taking all of this information into account, it is concluded that exposure to TCE does not present a carcinogenic hazard to man at levels of current occupational exposure standards.