Vinyl chloride hemangiosarcoma

Both benign and malignant liver tumors may arise from exposure to hepatotoxins and can be derived from various cell types. Thus, adenomas have been associated with the use of contraceptive steroids and exposure to aflatoxin Bi, and dimethylnitrosamine can produce hepatocellular carcinomas, whereas vinyl chloride causes hemangiosarcomas derived from the vasculature (see chap. 7). 

Vinyl chloride is a chemical used in the manufacture of plastics, which is carcinogenic and causes various toxic effects, including liver injury and damage to the bones and skin. Liver hemangiosarcomas are produced in animals and humans. Vinyl chloride undergoes metabolic activation by cytochrome P-450 to an epoxide, which may interact with DNA and form adducts (ethenodeoxyadenosine and ethenodeoxycytidine), which leads to mutations. These can be detected in white cells, and a mutant p21 ras protein can be detected in the serum of exposed workers. Also, reaction with GSH occurs. 

Vinyl chloride causes liver cancer (hemangiosarcoma), narcosis, and Raynaud s phenomenon that comprises scleroderma, acro-osteolysis, and liver damage. The appearance of liver tumors is dose dependent but reaches a maximum at about 22% incidence. This seems to be due to the fact that the metabolism that is necessary for the carcinogenicity, is saturated, and/or inhibited by vinyl chloride. The toxic metabolites produced are the epoxide and chloroacetaldehyde. 

Arguably the most clearly documented human carcinogen is vinyl chloride, which has been shown to cause a type of liver tumor called hemangiosarcoma, which is virtually unobserved except in workers heavily exposed to vinyl chloride.8 Up until about 1970, workers were exposed... 

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