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 oncogenicity studies, there is clear evidence that
styrene does not induce
cancer in rats.