Reproductive toxicological evaluation of Omadine MDS.
Reproductive toxicology studies with Omadine MDS were conducted using rats and rabbits, and plasma levels of the metabolite, 2-methylsulfonylpyridine (2-MSP), were assayed. In phase I (treated males, untreated females) of the fertility study, the no-effect level, for oral dosing, was 3.0 mg/kg; 7.5 mg/kg caused a decrease in male weight gain. In phase II (treated females, untreated males), the no-effect oral dose level was 1.0 mg/kg. At 3.0 mg/kg, decreases were seen in maternal body weight gain, the fertility index, and in total implantations and viable embryos at the 13-day uterine examination. Severe maternal toxicity including impaired motor function of limbs, decrease in weight gain, and mortality occurred at 7.5 mg/kg. In the perinatal/postnatal study, the no-effect level was 3.0 mg/kg. At 7.5 mg/kg, mortality was high, with a majority of animals dying during mid lactation. In the rat teratology study, the high dosage level, 30 mg/kg, dermally administered on Gestation Days 6 through 15 caused slight maternal toxicity, whereas 10 mg/kg produced none. These dosage levels corresponded to peak plasma levels on Gestation Day 10 of 470 and 1950 ng/ml 2-MSP at the 10- and 30-mg/kg dosage levels, respectively. In the rabbit, 5 mg/kg topically applied on Gestation Days 6 through 18 produced slight maternal toxicity while 1.5 mg/kg produced no maternal effects. The plasma levels of 2-MSP peaked on Days 12 and 15 of gestation. At 1.5 mg/kg these levels were 155 and 148 ng/ml; at 5.0 mg/kg, levels were 513 and 573 ng/ml. There was no teratogenic response seen in either species.