An inhalation reproductive toxicity study of octamethylcyclotetrasiloxane (D4) in female rats using multiple and single day exposure regimens

Octamethylcyclotetrasiloxane (D4) has been shown to have effects on the female rat reproductive cycle. This study evaluated the phase of the female rat reproductive cycle affected by D4 using a study design that allowed the complete female reproductive cycle, as well as phases of the cycle, from pre-mating through gestation, to be evaluated. Rats were exposed via whole body vapor inhalation up to 700 ppm D4 during the overall phase (28 days prior to mating through gestation day (GD) 19), the ovarian phase (31–3 days prior to mating), the fertilization phase (3 days prior to the start of mating through gestation day 3), and the implantation phase (GD 2–GD 5) of the reproductive cycle. D4 was associated with decreases in implantation sites and litter size in the overall and fertilization phases, but not in the ovarian or implantation phases. In order to further define the sensitive period for D4 exposure, additional groups of rats were exposed on single days. A single 6 h exposure to D4 on the day prior to mating resulted in a significant reduction in fertility. These data indicate that there is a very narrow window, around the time of ovulation and fertilization, for D4 to exert effects on the reproductive cycle of the female rat. Subsequent research, reported elsewhere, has elucidated the mode of action and assessed its potential relevance to humans.