Lifespan oral toxicity study of vinyl chloride in rats

Abstract

A lifespan oral toxicity study of vinyl chloride monomer (VCM) was carried out in Wistar rats, using five groups each of 60–80 males and 60–80 females. VCM was administered by incorporating polyvinyl chloride (PVC) powder with a high VCM content into the diet or by gastric intubation of a 10% VCM solution in soya-bean oil. The VCM doses (actual exposures) were 0 (control), 1·7, 5·0 and 14·1 mg/kg body weight/day provided by diets containing PVC powder, and 300 mg/kg body weight given by stomach tube as a solution of VCM in oil on 5 days/wk. The death rate was higher in all VCM-treated groups than in the controls and increased with increasing VCM doses. The 14·1- and 300-mg/kg treatments were associated with shortened blood-clotting times, slightly increased α-foetoprotein levels in the blood serum, liver enlargement and an increased haematopoietic activity in the spleen. A variety of neoplastic and non-neoplastic treatment-related liver lesions was found at each of the VCM levels. The changes varied from swollen and irregularly-shaped mitochondria in hepatocytes to hepatocellular carcinomas and hepatic angiosarcomas. The tumour response of the liver appeared to shift from a predominance of angiosarcomas at the highest dose level via a mixture of angiosarcomas and hepatocellular tumours at the intermediate levels to the exclusive development of hepatocellular tumours at the lowest VCM level. Tumours attributable to VCM exposure and found at other sites included pulmonary angiosarcomas, extrahepatic abdominal angiosarcomas and tumours of the Zymbal glands; these neoplasms occurred at VCM levels of 5·0 mg/kg and above. In addition, there was some evidence that VCM exposure enhanced the development of abdominal mesotheliomas and of adenocarcinomas of the mammary glands. Thus, the present study showed that orally administered VCM is a carcinogen in rats, and that the “no-observed-adverse-effect level” in rats was lower than 1·7 mg/kg body weight/day under the rigorous conditions of continuous oral VCM exposure resulting from the release of VCM from PVC powder present in the gastro-intestinal tract.