Title
Lifespan oral toxicity study of vinyl chloride in rats
Author
Feron, V.J.
Hendriksen, C.F.M.
Speek, A.J.
Til, H.P.
Spit, B.J.
Centraal Instituut voor Voedingsonderzoek TNO
Publication year
1981
Abstract
A lifespan oral toxicity 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 ??-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 hepato-cellular 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. Chemicals/CAS: polyvinylchloride, 9002-86-2; vinyl chloride, 75-01-4; Vinyl Chloride, 75-01-4; Vinyl Compounds
Subject
Polyvinylchloride
Animal experiment
Blood and hemopoietic system
Blood clotting
Carcinogenesis
Drug response
Drug toxicity
Hematopoiesis
Intoxication
Administration, Oral
Animal
Behavior, Animal
Body Weight
Eating
Female
Hemangiosarcoma
Liver
Liver Neoplasms
Lung
Lung Neoplasms
Male
Mammary Neoplasms, Experimental
Rats
Support, Non-U.S. Gov't
Vinyl Chloride
Vinyl Compounds
To reference this document use:
http://resolver.tudelft.nl/uuid:614378ad-dae0-43be-8890-39ecffc85de5
TNO identifier
229094
ISSN
0015-6264
Source
Food and Cosmetics Toxicology, 19 (3), 317-333
Document type
article