Hexamethyldisiloxane: A 13-Week Subchronic Whole-Body Vapor Inhalation Toxicity Study in Fischer 344 Rats

Hexamethyldisiloxane (HMDS) is a volatile linear siloxane dimer used in many applications, including precision cleaning, active ingredient carrier, and as a manufacturing intermediate. The purpose of this study was to characterize the subchronic vapor inhalation toxicity of the material as part of a comprehensive toxicology program. Groups of 20 male and 20 female Fischer 344 (F344) rats were exposed to nominal (and mean actual) vapor concentrations of 0, 50 (50), 200 (194), 600 (593), 1500 (1509) and 5000 (5012) ppm of HMDS, 6 hours per day, 5 days per week, for 13 weeks. No treatment-related signs of clinical toxicity or mortality, statistically significant effects upon body weight gain or food consumption, ophthahnoscopic changes, gross macroscopic necropsy findings, or organ weight changes were noted. Minor hematological, clinical biochemical, and urinalysis changes were seen but were not considered to be of toxicological relevance. Histological lesions in the kidney apparently consistent with male rat-specific α-2-urinary globulin nephropathy were observed in male rats exposed to 593, 1509, and 5012 ppm of HMDS, accompanied by slightly increased plasma urea and creatinine concentrations. No other treatment-related histological changes were seen in HMDS-exposed rats.