Vinyl chloride-induced hepatic angiosarcoma.

Abstract

In early 1974, an alert plant physician reported the occurrence of several cases of the otherwise rare hepatic angiosarcoma (HAS) at a single polyvinyl chloride (PVC) production facility in Louisville, Kentucky (U.S.A.). Upon further investigation, the relative risk for HAS at this plant appeared to be approximately 5,000, strongly indicating a causal relationship with some factor at the plant. Epidemiologic studies at this and other PVC polymerization plants identified vinyl chloride monomer (VCM) as the causative agent. Experimental studies reported in early 1974 confirmed VCM as a hepatic carcinogen capable of producing HAS and other tumors. Follow-up epidemiologic studies revealed that: 1) HAS is the end stage of a progressive liver disease consisting of hepatocytic and sinusoidal cell hyperplasia, sinusoidal dilatation, and hepatic fibrosis; 2) over 100 cases of VCM-induced HAS have occurred worldwide; and 3) an increased risk of lung cancer has been reported in some cohort studies of PVC polymerization workers, although this outcome may be related to PVC dust or factors other than VCM. A national study of HAS in the United States identified 3 other causes of HAS: Thorotrast, inorganic arsenic, and androgenic-anabolic steroids. Of 168 cases found to occur during 1964 through 1974, 42 cases (25%) were associated with the 4 known etiologic agents, while 126 cases (75%) were of unknown etiology.