Subchronic inhalation toxicity of tetramethoxysilane in rats

Sprague-Dawley rats were exposed 6 hr/day, 5 days a week, for 28 days to tetramethoxysilane (TMOS) at concentrations of 0, 1, 5, and 10 ppm (Phase I study) and to 0, 15, 30, and 45 ppm (Phase II study). All of the rats exposed to 45 ppm TMOS died or were sacrificed in a moribund state during the 28-day study period. Statistically significant changes were observed in food consumption, body weights, and clinical chemistry parameters in the animals exposed to 30 ppm TMOS. Males exposed to 15 ppm TMOS showed a significant decrease in total protein. No effects were seen in rats exposed to 1, 5, and 10 ppm TMOS. Histopathological lesions related to TMOS exposure were observed in the respiratory tract tissues and eyes of rats exposed to 15, 30, and 45 ppm TMOS. The principal types of lesions observed were ulceration, inflammation, and necrosis of epithelium. At 45 ppm, changes at these sites were severe and present in all animals. Changes at 30 ppm, while occurring in all rats, were much less severe than those seen at 45 ppm. At 15 ppm, the changes were minimal and occurred only in three males and five females. The data of this study showed that TMOS has a steep dose-response curve with no observable effects at 10 ppm, very minimal effects at 15 ppm, moderate to severe effects at 30 ppm, and severe effects and lethality at 45 ppm.