Reproductive and developmental toxicity studies of S-1090, cefmatilen hydrochloride hydrate (1)--A study on oral administration prior to and in the early stages of pregnancy in rats

Cefmatilen hydrochloride hydrate (S-1090) was administered daily by gavage to rats at doses of 100, 300 or 1000 mg potency/kg/day prior to and in the early stage of pregnancy to assess its adverse effects on parental reproductive ability and embryo-fetal development. Loose and/or reddish brown feces were observed in both males and females of all the S-1090 dosing groups, and abdominal distention was also observed in males throughout the dosing period. No drug-related deaths occurred in either males or females. In males, body weight and food consumption were increased at a dose of 1000 mg potency/kg/day throughout the dosing period. In females, body weight gain was restrained during late pregnancy, and food consumption was decreased transiently following the initiation of dosing, and then remained high on the day before parturition in all the S-1090 dosing groups. Necropsy of male and female rats revealed an increase in the cecum weight. The reproductive ability of males and females was normal in all the S-1090 dosing groups. No effects of S-1090 were observed in the implantation ratio, embryo-fetal viability, fetal body weight, and incidence of external, skeletal and visceral anomalies. Based on these results, the no observed adverse effect levels of S-1090 are estimated to be less than 100 mg potency/kg/day for parental general toxicity, 1000 mg potency/kg/day for reproductive toxicity, and 1000 mg potency/kg/day for developmental toxicity in embryo-fetuses under the conditions of the present study.