INHALATION TOXICOLOGY OF DECAMETHYLCYCLOPENTASILOXANE (D-5) FOLLOWINGA 3-MONTH NOSE-ONLY EXPOSURE IN FISCHER-344 RATS

D-5 is a low-molecular-weight cyclic siloxane used for industrial and consumer product applications. The objective of the present study was to evaluate the subchronic toxicity of D-5 following a 3-month nose-on ly inhalation exposure. In addition, animals from both sexes of the co ntrol and high dose groups were allowed a 4-week recovery period to ob serve reversibility, persistence, or delayed occurrence of any potenti al adverse effects. Male and female Fischer 344 rats were exposed for 6 h/day, 5 days/week for 3 months to target concentrations of 0 (30/se x/group), 26 (20/sex/group), 46 (20/sex/group), 86 (20/sex/group), and 224 (30/sex/group) ppm D-5. Recovery groups (0 and 224 ppm) comprised 10 rats/sex/group. Body weights and food consumption were monitored a t least twice weekly over the course of exposures. Approximately 16 h preceding euthanasia, animals were transferred into metabolism caging for urine collection and were fasted. Rats were anesthetized with pent obarbital and euthanized by exsanguination. Blood was collected for he matological and clinical biochemical analyses. Selected organ weights were measured and a complete set of tissues was taken for histopatholo gical examination. There were several minor changes observed in clinic al biochemistry parameters; the most notable was an increase in gamma glutamyl transferase (gamma-GT) in both sexes at the high dose. In fem ales, this effect was dose-related (46-224 ppm) and did not recover up on cessation of exposure. Additionally, there was an decrease in serum lactate dehydrogenase (LDH) observed in females at 86 and 224 ppm whi ch was not resolved during recovery. There was an increase in absolute and/or relative liver weight in rats of both sexes. Taken together, t hese data suggest that the female rat is more sensitive to the actions of D-5 on the liver. Exposure-related increases in absolute and relat ive lung weights were observed in both sexes at terminal necropsy. Thi s observation was not noted in males in the recovery phase, but was st ill present in females. Finally, histopathological evidence indicated the primary target organ following D-5 inhalation exposure is the lung , with an increase in focal macrophage accumulation and interstitial i nflammation in the lungs of male and female rats exposed to 224 ppm D- 5. This observation did not appear to resolve at the end of a 1-month period of nonexposure. The incidence of these changes was also slightl y increased in rats of both sexes exposed to 86 ppm D-5. These data su ggest that nose-only D-5 vapor inhalation provokes minimal changes in the lung which are similar in incidence and severity to spontaneously occurring changes in control animals after nose-only exposures. There were no histopathological findings noted in the livers which support t his organ as a target in this study, despite the observed changes in o rgan weight and in some serum chemistry parameters. (C) 1998 Society o f Toxicology.