14-day Oral Gavage Study of Octamethylcyclotetrasiloxane in Female Rabbits with Cover Letter Dated 05/11/1992

摘要

A 14-day oral gavage study was conducted to determine effects associated with ingestion of dimethylcyclosiloxane fluid. This study was a follow-up to a range-finding study in which pregnant rabbits consumed less food and had significantly decreased body weights compared to controls. The purpose of this study was to determine if these effects were specific to pregnant rabbits. Groups of six non-pregnant New Zealand White female rabbits were administered 0, 500 or 1000 mg/kg/day of dimethylcyclosiloxane fluid (99.8% pure) suspended in 0.5% Methocel in distilled water via oral gavage, seven days a week for 14 days. Control animals were administered 0.5% Methocel in distilled water in the same manner. Following the first week of exposure, doses were adjusted to reflect body weight changes. The rabbits were observed for signs of toxicity, appearance, behavioral changes, local or systemic toxicity, and mortality. Body weights and food consumption were recorded. On day 14 of the study, animals were sacrificed and gross necropsy performed on all major organs and tissues. There were statistically significant decreases in body weight gains and food consumption in both treated groups when compared to control animals. There was a marked decrease in the size of the thymus in all of the low dose animals and 4 of 6 of the high dose animals. This effect was not seen in the control animals. Although these effects were statistically significant in the treated animals they were not dose related. The decrease in thymus size was considered to be a secondary effect of weight loss (attributed to a decrease in food consumption) and acute stress from the dosing procedure.