[Reproductive and developmental toxicity study of S-1090, cefmatilen hydrochloride hydrate (3)--A study on oral administration during the period of organogenesis in rabbits].
Cefmatilen hydrochloride hydrate (S-1090) at dosage levels of 6.25, 12.5 and 25 mg potency/kg/day was administered orally by gavage to groups of 13-16 pregnant rabbits daily during the period of organogenesis, and the effects of S-1090 on dams and fetuses were examined. Control animals were treated with a 0.5 w/v% aqueous solution of methylcellulose. Abortion was noted in 1 of the 16 females of the 12.5 mg potency/kg group and in 1 of the 14 females of the 25 mg potency/kg group, and death was noted in 1 of the 14 females of the 25 mg potency/kg group. Regarding the dams, decreased food consumption was noted in the 12.5 mg potency/kg group in the beginning of the dosing period. Suppressed body weight gain and decreased food consumption were noted in the 25 mg potency/kg group during the pregnancy period. At necropsy, thickening of the gastric mucosa, hemorrhage in the cecum, and higher values of cecum weight were also noted in this group. On the other hand, no effects of S-1090 were noted in general signs, body weight changes, food consumption, necropsy findings, or organ weights in the 6.25 mg potency/kg group. No effects of S-1090 were noted in the number of corpora lutea, number of implantations, implantation rate, death or resorption rate, number of live fetuses, sex ratio of live fetuses, fetal body weight of either sex, incidence of external anomalies, incidence of skeletal anomalies or variations, degree of ossification, or incidence of visceral anomalies. On the basis of the above results, the no observed adverse effect levels of S-1090 are estimated at 6.25 mg potency/kg/day for general toxicity and reproductive functions in dams, and at 25 mg potency/kg/day for development in fetuses under the conditions of the present study.