Lifetime (149-week) oral carcinogenicity study of vinyl chloride in rats.
A lifetime (149-wk) oral carcinogenicity study of vinyl chloride monomer (VCM) was carried out. Four groups of Wistar rats were used, each consisting of 100 males and 100 females, except for the high-dose group, which comprised 50 males and 50 females. VCM was administered by incorporating polyvinyl chloride powder with a high content of VCM into the diet. The actual exposure levels of VCM were 0 (control), 0.014, 0.13 and 1.3 mg VCM/kg body weight/day. Detailed histopathological examination was restricted to the liver. In the final stage of the study, the mortality in the high-dose group was slightly higher than in controls. A variety of VCM-related liver lesions was found in the high-dose group. The lesions included increased incidences of liver-cell polymorphism, hepatic cysts, foci of cellular alteration, neoplastic nodules, hepatocellular carcinomas and angiosarcomas. Compared with controls, there were increased incidences of hepatic foci of cellular alteration in females of the mid-dose group and of basophilic foci of hepatocellular alteration in females of both the low- and mid-dose groups. There was no evidence that feeding of VCM affected the incidence of tumours in organs other than the liver. Thus, the present study showed that the feeding of VCM at a level of 1.3 mg/kg body weight/day can induce neoplastic and non-neoplastic changes in the livers of male as well as female rats. The feeding of 0.014 or 0.13 mg VCM/kg body weight/day may result in an increased incidence of (basophilic) foci of cellular alteration in the liver of female rats. It was concluded that 0.13 mg VCM/kg body weight/day is the no-observed-adverse-effect level with respect to the induction of tumours in rats.
Til
H P
HP
TNO Toxicology and Nutrition Institute, Zeist, The Netherlands.
Feron
V J
VJ
Immel
H R
HR
D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000401:mortality; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014752:Vinyl Chloride / Q000008:administration & dosage / Q000633:toxicity*
D002273:Carcinogens; D014752:Vinyl Chloride