No abstract

Exposure of mice to 50, 250, or 1000 ppmm of vinyl chloride (VC) in the air for 6 h/d, 5 d/wk, caused a high incidence of bronchioloalveolar adenoma, mammary gland tumors, and hemangiosarcoma. Mammary gland tumors occurred in the females and included ductular adenocarcinoma and squamous and anaplastic cell carcinomas with metastasis to the lung. Hemangiosarcoma occurred in the liver and, to a lesser extent, in various other organs. The incidence and severity of these tumors increased with the concentration of VC and the length of exposure. Malignant lymphoma involving various organs was observed in several mice. Rats were more resistant to the carcinogenic effects of VC. Exposure of rats to 250 or 1000 ppm of VC caused hemangiosarcoma in the liver. Many rats with hepatic hemangiosarcoma also developed hemangiosarcoma in the lung. Extrahepatic hemangiosarcoma also occasionally occurred in other organs. Exposure to 55 ppm of vinylidene chloride (VDC) caused hepatic hemangiosarcoma and probably bronchioloalveolar adenoma in mice. Hemangiosarcoma also occurred in the mesenteric lymph node or subcutaneous tissue in two rats exposed to 55 ppm of VDC.

Carcinogenic and other toxic effects in rats and mice were examined during a 12-mo period following exposure to vinyl chloride (VC) or vinylidene chloride (VDC). Exposure of male and female mice to 50, 250, or 1000 ppm VC for 6 h/d, 5 d/wk, for 1, 3, or 6 mo resulted in increased numbers of deaths and increased moribundity at all dose levels during the exposure and postexposure periods, as compared with air-exposed controls. Similar observations were made with rats after 1, 3, 6, or 10 mo exposure to VC. Cumulative tumor incidence at various organ sites also increased in both species during the postexposure period in proportion to dose or duration of exposure at higher dose levels. However, except for mammary gland tumors in female mice, no significant increase in cumulative tumor incidence occurred in either species at 50 ppm VC or 55 ppm VDC, regardless of duration of exposure. These results suggest that exposure to vinyl halides at dose levels lower than those that elicit a significant increase in cancer incidence during the lifetime of the animal may, nonetheless, increase the risk of early death or moribundity from toxic pre- or subcarcinogenic effects. At dose levels higher than those consistent with the physiological defense or repair capabilities of the cell, ultimate tumor incidence becomes proportionate to length of exposure and may reflect the number of carcinogenic events elicited during the exposure period.