Komae N, Sanzen T, Kozaki T, Ohba E, Kawamura Y, Kodama T
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Jpn J Antibiot. 1995 Jun;48(6):832-60.
We carried out reproductive and developmental toxicity studies (i.e. fertility study, teratological study, and perinatal and postnatal study) of T-3761, a new quinolone derivative, in S.D. rats. T-3761 was administered orally at the dose of 60, 300 and 1,500 mg/kg/day as suspension in 5% acacia solution. 1. Fertility study T-3761 was administered to male rats for 9 weeks prior to mating and to female rats for 2 weeks prior to mating and until day 7 of gestation. In parent rats, soft stools, slight depression of body weight gain and increase in water intake were observed at the dose of 1,500 mg/kg. Cecum weight was increased at the dose of 300 mg/kg and more in male and at the dose of 1,500 mg/kg in female. No effects on reproductive performance were discernible in the T-3761 treated groups. In fetuses, external, skeletal and visceral examinations revealed no teratological abnormalities. Slightly retarded ossification, however, was observed at the dose of 1,500 mg/kg. From these findings, the no-effect dose of T-3761 in fertility study was considered to be 300 mg/kg/day for parent rats and fetuses. 2. Teratological study T-3761 was administered from day 7 to day 17 of gestation. In dams, soft stools, transient decrease in food intake, increase in water intake, depression of body weight gain and increase in cecum weight were observed at the dose of 1,500 mg/kg. In fetuses, slight increase in incidence of ventricular septal defect and slightly retarded ossification were observed at the dose of 1,500 mg/kg. In the postnatal examination, there were no effects in the T-3761 treated groups. From these findings, the no-effect dose of T-3761 in teratological study was considered to be 300 mg/kg/day for dams and next generations. 3. Perinatal and postnatal study T-3761 was administered from day 17 of gestation to day 21 of lactation. In dams, cecum weight was increased at the dose of 300 mg/kg and more. And soft stools, transient decrease in food intake, increase in water intake, transient depression of body weight gain and slight extension of gestation period were observed at the dose of 1,500 mg/kg. In the postnatal examination, there were no effects in the T-3761 treated groups. From these findings, the no-effect dose of T-3761 in perinatal and postnatal study was considered to be 300 mg/kg/day for dams and more than 1,500 mg/kg/day for next generations.
我们在SD大鼠中开展了新型喹诺酮衍生物T-3761的生殖与发育毒性研究（即生育力研究、致畸学研究以及围产期和产后研究）。T-3761以悬浮于5%阿拉伯胶溶液中的形式，按60、300和1500 mg/kg/天的剂量口服给药。1. 生育力研究 T-3761在交配前对雄性大鼠给药9周，对雌性大鼠在交配前给药2周并持续至妊娠第7天。在亲代大鼠中，1500 mg/kg剂量组出现软便、体重增加略有下降和饮水量增加。雄性大鼠300 mg/kg及以上剂量组和雌性大鼠1500 mg/kg剂量组盲肠重量增加。T-3761处理组的生殖性能未见明显影响。在胎儿中，外观、骨骼和内脏检查未发现致畸异常。然而，在1500 mg/kg剂量组观察到骨化略有延迟。根据这些结果，生育力研究中T-3761对亲代大鼠和胎儿的无作用剂量被认为是300 mg/kg/天。2. 致畸学研究 T-3761在妊娠第7天至第17天给药。在母鼠中，1500 mg/kg剂量组出现软便、食物摄入量短暂减少、饮水量增加、体重增加受抑制和盲肠重量增加。在胎儿中，1500 mg/kg剂量组观察到室间隔缺损发生率略有增加和骨化略有延迟。产后检查中，T-3761处理组未见影响。根据这些结果，致畸学研究中T-3761对母鼠和下一代的无作用剂量被认为是300 mg/kg/天。3. 围产期和产后研究 T-3761在妊娠第17天至哺乳期第21天给药。在母鼠中，300 mg/kg及以上剂量组盲肠重量增加。1500 mg/kg剂量组出现软便、食物摄入量短暂减少、饮水量增加、体重增加短暂受抑制和妊娠期略有延长。产后检查中，T-3761处理组未见影响。根据这些结果，围产期和产后研究中T-3761对母鼠的无作用剂量被认为是300 mg/kg/天，对下一代则超过1500 mg/kg/天。
