Document aG5rM8yQLVR6keOkBRLnZ6va

' '' RECEIVED J/ifj [ o 1977 EVALUATION OF THE EHV V RONMKHTAL TOXICANTS VINYL CHLORIDE (VC) AND VINYLIDKHE CHLORIDE (VDC) by Chcng-Chun Lee Joseph M. Winston Paul J. Peters Jagdish C. Bhandari John R. Hodgson Jack H. Hagensen Thomas W. Reddig Ellen R. Ellis PROGRESS REPORT NO. 10 1 April through 30 June 1976 Contract No. N01-ES-2-2084 (Continuation of NIH-NTEHS-72-2-2084) J;. j .H-A i/ LP Cf MRI Project No. 3612-B For National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park, NC 27709 Attn: James S-. Woods 0007B39 EVALUATION OK THE ENVIRONMENTAL TOXICANTS VINYL CHLORIDE (VC) AND VIKYLIDENE CHLORIDE (VDC) (Progress Report No. 10) ABSTRACT This report summarizes the results of 9 months exposure to various levels of vinyl chloride (VC) and one level of vinylidene chloride (VDC) in rats and mice. At the end of 9 months exposure of rats to 50, 250, or 1,000 ppm VC, or 55 ppm VDC for 6 hours/day, 5 days/week, a number of adverse effects were found. Between the 33rd and 39th week, one male and three female rats exposed to VC died or were terminated. A number of tumors were found in these rats as well as in some of the rats terminated at the, end of 9 months exposure to VC. Hemangiosarconas were observed in liver, lung and adrenal! gland of rats exposed to 250 or 1,000 ppm VC. The tumor incidence was higher in the rats exposed to 1,000 ppm VC than in rats exposed to 250 ppm VC. The. body weignt gain of female rats exposed to 1,000 ppm VC was slightly depressed. Exposure to 55 ppm VDC caused one subcutaneous hemangiosarcoma of the skin. Exposure to 55 ppm VDC slightly depressed the body weights of both male and female rats. At the end of 9 months exposure to VC or VDC, no adverse changes in clinical laboratory data occurred. Exposure of mice to 50, 250, or 1,000 ppra VC resulted in a large number of deaths or early terminations during the 7- to 9-month period. The clinical signs in these mice included rough hair coat, lethargy, sudden 1 weight loss and the appearance of external tumor masses and/or abdominal dis tention. The majority of mice terminated during the 7- to 9-month period had tumors in more than one tissue. The major tumors found were bronchiolar adenoma and/or metastatic mammary gland squamous cell carcinoma or anaplastic carcinoma in the lung; hemangiosarcoma in the liver; and ductular adeno carcinoma, squamous cell carcinoma and/or anaplastic carcinoma in the mammary gland.. Other tumors found Included malignant lymphoma, hemangioma or hemangiosarcoma of'various tissues. The incidence and severity of the bronchiolar adenomas were dose related. A threshold level of exposure greater than 50 ppm VC for the induction of hepatic angiosarcoma appeared to exist. The ex posure to.VC.caused no apparent changes in clinical laboratory data with the exception of increased pulmonary macrophage counts in the 1,000 ppm VC ex posed male mice. Exposure to 55 ppm VDC resulted tumors In three mice. These tumors included bronchiolar adenoma in lung and hemangiosarcoma or hepatoma in the liver. Other lesions which appeared to be related Co the VDC exposure were intranuclear inclusions and an increase in the number of large, basophilic nuclei. No adverse changes in clinical laboratory data were noted. iv RSV 0007840