||Dow Corning Corp., Midland, MI.; Huntingdon Life Sciences, Ltd., Princeton, NJ.; Environmental Protection Agency, Washington, DC. Office of Toxic Substances.
The objective of this study was to assess the effects of Dow Corning 200 Fluid, 350 cSt, upon the progress and outcome of pregnancy in New Zealand White rabbits. The study was performed in general compliance with the United States Environmental Protection Agency Guideline, Title 40, Part 798 (Toxic Substances Control Act, July 1989) and taking into account the EPA Health Effect Test Guideline OPPTS 870.3700 'Public Draft', February 1996. The exception to this draft guideline was that the animals were not dosed from Day.20 to Day 29 after mating because of potential practical problems associated with dermal administration. Dow Corning 200 Fluid, 350 cSt was administered by dermal application to three groups of 23 pregnant female New Zealand White rabbits from Day 6 to Day 19 after mating at dosages of 33, 300 or 1000 mg/kg/day. The test substance was removed after six hours of exposure on each day of treatment. A similarly constituted fourth group, serving as Controls (Sham Controls), were subjected to the same procedures as the treated animals, but no test substance was applied. Throughout the study, signs associated with treatment and body weights were recorded daily and food consumption was recorded over five specified periods. The dermal application sites were examined daily for signs of irritation from Day 6 after mating until termination. On Day 29 after mating, the females were sacrificed to allow examination of their uterine contents. The fetuses were examined at necropsy and following skeletal processing, except for the heads from half of the fetuses which were examined following f ice-hand serial sectioning. The general condition of the treated animals was similar to that of the Controls and there were no adverse signs considered to be related to treatment. A higher incidence of ungroomed coat was observed for females receiving 300 or 1000 mg/kg/day when compared with the Controls. This was considered to be as a result of the accumulation of test substance around the application site. One female in Group 4 aborted on Day 29 of gestation and one female in the Control group had total litter resorptions. The incidence and distribution of these fmdings were not indicative of an effect of treatment. Six females were not pregnant; one in the control group and five treated at 33 mg/kg/day. The distribution of these findings was incidental and not related to treatment. Bodyweight, bodyweight change and food consumption were not considered to be affected by treatment. Macroscopic examination of the females did not reveal any toxicologically-significant treatment-related fmdings. Litter parameters were considered to be unaffected and fetal examination revealed a number of abnormalities in both the Control and treatment groups, however none were considered to be attributable to treatment with Dow Corning 200 Fluid, 350 cSt. It was concluded from this study that the No-Observed-Effect-Level (NOEL) of Dow Corning 200 Fluid, 350 cSt on maternal condition or embryo-fetal development in the rabbit was 1000 mg/kg/day.