Support: Inhalation Reproductive Toxicity Study of Octamethylcyclotetrasiloxane (D4) in Female Rats using Multiple and Single Day Exposure Regimens, with Cover Letter dated 07/07/1999

摘要

In several earlier and previously reported single generation reproductive toxicity studies, rats were exposed to high concentrations of octamethylcyclotetrasiloxane (OMCTS) for a prolonged premating interval (at least 28 consecutive days). Exposures continued during the mating period, throughout gestation, and (in some studies) during lactation. In these studies, decreased litter sizes, decreased numbers of uterine implantations, and reduced numbers of corpora lutea were seen; these findings were previously communicated to EPA. In an ongoing, previously reported two generation inhalation reproductive toxicity study in male and female rats, a reduction in mean live litter size was seen in litters produced by both Fo and FI animals. Mating and fertility indices were reduced among Fr rats and some FI female rats displayed signs of prolonged diestrous. The decreased mating and fertility indices are likely due, at least in part, to the increased numbers of females in diestrous; it is well known that female rats in diestrous will not mate. The study which is the subject of this supplemental submission was conducted to evaluate the temporal responsiveness of female rats to the reproductive effects of OMCTS. Female rats were exposed by whole-body inhalation for six hours daily to the 700 ppm of test article at different times during the pre-mating and post- mating phases of their reproductive cycles. Lapohysterectomies were performed on gestation day 8, and corpora lutea and uterine contents were examined. Toxicity was expressed in some segments of the pre-mating phase by a reduced pregnancy rate and effects on mean body weight gains, reduced food consumption, and/or reduced numbers of mean corpora lutea and implantation sites, increased numbers of small implantation sites, and reduced mean uterine weight for different treatment regimens. In the post-mating phase, mean numbers of corpora lutea and implantation sites, pre-implantation losses, and numbers of small implantation sites were unaffected under all treatment regimens, with toxicity being expressed in a single group by reduced mean body weight gain and food consumption. The effects we are reporting occurred only at exposure concentrations that greatly exceed typical occupational or consumer exposures. Consequently, we believe that the results of this study are not indicative of a substantial risk to human health or the environment. Nevertheless, we are reporting these findings to EPA to ensure our compliance with both the letter and the spirit of TSCA Section 8(e).