Trichloroethylene Induced Cancer in Animals and Its Relevance to Humans

Trichloroethylene Induced Cancer in animals and its relevance to Humans : Trevor G reen . Zeneca Central Toxicology Laboratory —Tri‐chloroethylene has been manufactured on an industrial scale since the beginning of this century. During that time widespread human exposure has occurred in industry and in the general population through the environment and from its uses in medicine, food and consumer products. Following the discovery in 1976 that trichloroethylene was an animal carcinogen, there have been numerous animal toxicology and human epidemiology studies evaluating the risks associated with exposure to this chemical. Tri‐chloroethylene has been shown to cause tumours in both rats and mice in lifetime bioassays, principally liver and lung tumours in the mouse and kidney tumours in the rat. The mechanisms involved in the development of these tumours have been studied in detail and have been shown to be either species specific or a result of the use of cytotoxic dose levels. There is little or no evidence for genotoxicity playing a major role in these mechanisms. In mice, liver tumours are associated with peroxisome proliferation and increased cell division, the lung tumours are linked to cell damage and increased cell division. None of these effects are seen in rats due to metabolic and pharmacokinetic differences nor can they be replicated in human tissues. The low incidences of rat kidney tumours seen in some cancer bioassays appear to be linked to high dose toxicity. Human epidemiology studies based on large well defined cohorts support the findings of the mechanistic studies in animals and the overall conclusions that trichloroethylene is not a cancer hazard at current occupational and environmental levels.