Vinyl chloride induced angiosarcoma

The hazards of chemicals are commonly detected in the workplace first, because exposure levels there are higher than in the general environment. In addition, the exposed population is well known, which allows early detection of the association between deleterious health effects and the exposure. The toxic effects of some chemicals, such as mercury compounds and soot, have been known already for centuries. Already at the end of the eighteenth century, small boys who were employed to climb up the inside of chimneys to clean them suffered from a cancer of the scrotum due to exposure to soot. This was the first occupational cancer ever identified. In the viscose industry, exposure to carbon disulfide was already known to cause psychoses among exposed workers during the nineteenth century. As late as the 1970s, vinyl chloride was found to induce angiosarcoma of the liver, a tumor that was practically unknown in ocher instances. ... 

Popper H, Thomas LB, Telles NC. 1978. Development of hepatic angiosarcoma in man induced by vinyl chloride, Thorotrast, and arsenic. Comparison with cases of unknown etiology. Am J Pathol 92 349- 376. 

Medical surveillance also includes monitoring for a single case of new disease caused by a chemical agent that triggers an alarm in an astute clinician. Such cases, called sentinel events, result in further study and analysis to determine a true cause and effect relationship. Historically, numerous chemical agent induced disease processes have been determined through medical surveillance and sentinel event determination. For example, the relationship between vinyl chloride exposure and hepatic angiosarcoma development was determined by astute medical surveillance. 

CHAPTER 21 PBPK MODELS IN CANCER RISK ASSESSMENT TABLE 21.4. Dose-Response Assessment for Angiosarcoma Induced by Vinyl Chloride... 

Vinyl chloride (VC) has been reported to induce angiosarcoma of the liver in exposed animals and workers [e.g., Gehring et al. (1978, 1979)]. The dose-response... 

In the mid 1970 s, a number of publications appeared that demonstrated that vinyl chloride induced angiosarcoma of the liver in workers in the polyvinyl chloride manufacturing industry [5,7]. Subsequently, a number of biochemical studies, focussing on vinyl chloride metabolism in the liver, were published. Barbin et al. [8] demonstrated that, in Ihe presence of oxygen and NADPH, vinyl chloride was transformed to... 

In human liver angiosarcomas associated with occupational exposure to vinyl chloride, Marion et al. (1991) found that 5 out of 6 tumours contained a Ki-ras gene activated by a GC—>AT transition at the second base of codon 13. Ras gene mutations in vinyl chloride-induced liver tumours are carcinogen-specific but vary with cell type and species (Boivin-Angele et al. 2000). 

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