Division of Risk Assessment, Biological Safety Center, National Institute of Health Sciences, Tokyo, Japan.
Reprod Toxicol. 2010 Jun;29(3):292-7. doi: 10.1016/j.reprotox.2010.01.012. Epub 2010 Feb 2.
This study evaluated the prenatal developmental toxicity of the pesticide 2-sec-butyl-4,6-dinitrophenol (dinoseb). Pregnant rats were given dinoseb by gavage at 0, 8.0 or 10 mg/kg bw/day on days 6-15 of gestation, or in the diet at 0, 120 or 200 ppm (0, 6.52 or 8.50 mg/kg bw/day) on days 6-16 of gestation, and litters were evaluated on day 20 of gestation. Maternal toxicity was observed as evidenced by significantly decreased body weight gain and reduced food consumption during the administration period in all the dinoseb-treated groups, and two dams died at 10 mg/kg bw/day. Significantly lower fetal weights and delayed skeletal ossification was observed in the dinoseb-treated groups except for the group fed dinoseb at 120 ppm. The teratogenic potential of the gavage dose of dinoseb was confirmed as evidenced by increased incidences of fetuses with external and skeletal malformations at 10 mg/kg bw/day. The incidence of fetuses with microphthalmia was significantly increased at this dose. On the other hand, feeding doses of dinoseb up to 200 ppm did not induce teratogenicity in this study. These data indicate that dinoseb is teratogenic at maternally toxic doses, but the exposure range of dinoseb at which malformations occur seems to be narrow.
本研究评估了农药 2-仲丁基-4,6-二硝基苯酚(敌草净)的产前发育毒性。妊娠大鼠在妊娠第 6-15 天经灌胃给予敌草净 0、8.0 或 10mg/kg bw/天,或在妊娠第 6-16 天通过饮食给予 0、120 或 200ppm(0、6.52 或 8.50mg/kg bw/天),并在妊娠第 20 天评估胎仔。所有敌草净处理组均观察到母体毒性,表现为给药期间体重增长明显减少和食物摄入量减少,10mg/kg bw/天组有 2 只母鼠死亡。除 120ppm 敌草净喂养组外,敌草净处理组的胎仔体重明显降低,骨骼骨化延迟。灌胃剂量的敌草净致畸潜力得到证实,表现为 10mg/kg bw/天组胎仔的外部和骨骼畸形发生率增加。该剂量下小眼畸形的胎仔发生率也显著增加。另一方面,本研究中,敌草净的饲料剂量高达 200ppm 时并未引起致畸性。这些数据表明,敌草净在母体毒性剂量下具有致畸性,但发生畸形的敌草净暴露范围似乎较窄。