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© 1998 Oxford University Press
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Chronic Toxicity/Oncogenicity Study of Styrene in CD Rats by Inhalation Exposure for 104 Weeks
* ToxWorks, 39 Manners Road, Ringoes, New Jersey 08551
Chevron Research and Technology Company P.O. Box 1627, Richmond, California 94802
ARCO Chemical Company 3801 West Chester Pike, Newtown Square, Pennsylvania 19073
Shell Canada Ltd. 400 4th Avenue, Southwest, Calgary, Alberta, Canada T2P 2H5
||The Dow Chemical Co. Midland, Michigan 48674
¶Huntingdon Life Sciences, Huntingdon Research Centre P.O. Box 2, Huntingdon, Cambs., PE18 6ES, England
**Research Pathology Services 438 East Butler Avenue, New Britain, Pennsylvania 18901
Groups of 70 male and 70 female Charles River CD (Sprague-Dawley-derived) rats were exposed whole body to styrene vapor at 0, 50, 200, 500, or 1000 ppm 6 h/day 5 days/week for 104 weeks. The rats were observed daily, body weights and food and water consumption were measured periodically, and a battery of hematologic and clinical pathology examinations was conducted at weeks 13, 26, 52, 78, and 104. Nine or 10 rats per sex per group were necropsied after 52 weeks of exposure and the remaining survivors were necropsied after 104 weeks. Control and high-exposure rats received a complete histopathologic examination, while target organs, gross lesions, and all masses were examined in the lower exposure groups. Styrene had no effect on survival in males, but females exposed to 500 or 1000 ppm had a dose-related increase in survival. Levels of styrene in the blood at the end of a 6-h exposure during week 95 were proportional to exposure concentration. Levels of styrene oxide in the blood of rats exposed to 200 ppm or greater styrene were proportional to styrene exposure concentration. There were no changes of toxicologic significance in hematology, clinical chemistry, urinalysis, or organ weights. Males exposed to 500 or 1000 ppm gained less weight than the controls during the first year and maintained the difference during the second year. Females exposed to 200, 500, or 1000 ppm gained less weight during the first year; those exposed to 500 or 1000 ppm continued to gain less during months 13–18. Styrene-related non-neoplastic histopathologic changes were confined to the olfactory epithelium of the nasal mucosa. There was no evidence that styrene exposure caused treatment-related increases of any tumor type in males or females or in the number of tumor-bearing rats in the exposed groups compared to controls. In females, there were treatment-related decreases in pituitary adenomas and mammary adenocarcinomas. Based on an overall evaluation of eight onco-genicity studies, there is clear evidence that styrene does not induce Cancer in rats.
Key Words: styrene; inhalation; CRL-CD (Sprague-Dawley) rats; nasal irritation; olfactory epithelium; decreased mammary tumors; decreased pituitary tumors; oncogenicity.
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