Studies of the toxicological potential of capsinoids: IX. Teratology studies of dihydrocapsiate in rats and rabbits.

In order to determine the safety of dihydrocapsiate (4-hydroxy-3-methoxybenzyl 8-methylnonanoate; CAS no. 205687-03-2), teratology studies were conducted in pregnant Sprague-Dawley rats (18 to 20 animals per group) and pregnant New Zealand white rabbits (20 to 21 animals per group). The test substance was administered by gavage for 11 days, from days 7 to 17 of gestation in rats, and for 13 days from days 6 to 18 of gestation in rabbits, at dose levels of 0 (vehicle), 100, 300, or 1000 mg/kg/day. In the rat study, no deaths occurred in any group and there were no test substance-related changes or abnormalities in clinical signs, body weight, food consumption, or gross pathological findings. There were no test substance-related changes in the number of corpora lutea, number of implantations, index of implantations, index of embryofetal deaths, and number, sex ratio, or body weight of live fetuses at the end of the gestation period and there were no abnormalities in the placentae of live fetuses. There were no test substance-related abnormalities or variations in the external, skeletal, or visceral examinations of live fetuses. There were no abnormalities in ossification. En toto, it was concluded there were no teratogenic effects in the rat study. In the rabbit study, there were no test substance-related effects on clinical signs, body weight, food consumption, or necropsy findings in any group. There were neither test substance-related abortions nor test substance-related effects on the number of corpora lutea, number of implantations, or implantation index in any group. There were no test substance-related effects on the number of dead embryos/fetuses, the number, sex ratio, or body weight of live fetuses, or gross pathological finding of placentae. There were no test substance-related external abnormalities, or incidence of visceral or skeletal abnormalities or variations, and there were no test substance-related effects on the progress of ossification in any group. Based upon these data, the no observed adverse effect level (NOAEL) of dihydrocapsiate for general toxicity in dams, reproductive functions of dams, and embryofetal development was judged to be 1000 mg/kg/day both in rats and rabbits.