Vinyl chloride: Still a cause for concern

Vinyl chloride (VC) is both a known carcinogen and a regulated chemical, an d its production capacity has almost doubled over the last 20 years, curren tly 27 million tons/year worldwide. According to recent reports it is still a cause for concern. VC has been found as a degradation product of chloroe thylene solvents (perchloroethylene and trichloroethylene) and in landfill gas and groundwater at concentrations up to 200 mg/m(3) and 10 mg/L, respec tively. Worldwide occupational exposure to VC still seems to be high in som e countries (e.g., averages of approximately 1,300 mg/m(3) until 1987 in on e factory), and exposure may also be high in others where VC is not regulat ed. By combining the most relevant epidemiologic studies from several count ries, we observed a 5-fold excess of liver cancer, primarily because of a 4 5-fold excess risk from angiosarcoma of the liver (ASL). The number of ASL cases reported up to the end of 1998 was 197 worldwide. The average latency for ASL is 22 years. Some studies show a small excess risk for hepatocellu lar carcinoma, and others suggest a possible risk of brain tumors among hig hly exposed workers. Lung cancer, lymphomas, or leukemia do not seem to be related to VC exposure according to recent results. The mutation spectra ob served in rat and human liver tumors (ASL and/or hepatocellular carcinoma) that are associated,vith exposure to VC are clearly distinct from those obs erved in sporadic liver tumors or hepatic tumors that are associated with o ther exposures. In rats, the substitution mutations found at A:T base pairs in the ras and p53 genes are consistent with the promutagenic properties o f the DNA adduct 1,N-6-ethenoadenine formed from VC metabolites. Risk asses sments derived from animal studies seem to overestimate the actual risk of cancer when comparing estimated and reported cases of ASL.