Rogers J M, Carver B, Gray L E, Gray J A, Kavlock R J
Teratog Carcinog Mutagen. 1986;6(5):375-81. doi: 10.1002/tcm.1770060504.
The teratogenic potential of the fungicide dinocap was evaluated in CD-1 mice. Pregnant mice were dosed by intubation with dinocap in corn oil on gestation days 7-16. Doses used were 0, 5, 10, 20, 40, 80, and 120 mg/kg/day, based on day 6 weight. Dams were killed on day 18, at which time fetuses were counted, weighed, and preserved for necropsy or skeletal examination. The highest dose killed 80% of the dams dosed, while 29% of the dams in the 80 mg/kg group died during dosing. There was no dose-related maternal mortality at lower doses. Net maternal weight gain was affected only at 80 mg/kg/day. There were no live fetuses at 120 mg/kg/day. The number of live fetuses per litter was decreased and resorptions increased at 80 mg/kg. Dose-related decreases in gravid uterus weight and fetal weight were significant at all doses of dinocap. Cleft palate was found in fetuses at 5(1/234; 0.4%), 20(46/195; 23.6%), 40(140/185; 75.5%), and 80(63/85; 74.1%) mg/kg/day. There was a dose-related increase in supernumerary ribs and a low frequency of exencephaly and umbilical hernia at high doses. This study shows that dinocap is teratogenic in the CD-1 mouse at doses well below those causing maternal toxicity.
在CD-1小鼠中评估了杀真菌剂敌菌丹的致畸潜力。妊娠第7至16天,通过灌胃给怀孕小鼠施用溶于玉米油的敌菌丹。根据第6天的体重,使用的剂量分别为0、5、10、20、40、80和120mg/kg/天。在第18天处死母鼠,此时对胎儿进行计数、称重,并保存用于尸检或骨骼检查。最高剂量导致80%接受给药的母鼠死亡,而80mg/kg组有29%的母鼠在给药期间死亡。较低剂量下没有与剂量相关的母鼠死亡率。仅在80mg/kg/天时母体净增重受到影响。120mg/kg/天时没有活胎。80mg/kg时每窝活胎数量减少,吸收增加。在所有敌菌丹剂量下,妊娠子宫重量和胎儿体重的剂量相关下降均显著。在5(1/234;0.4%)、20(46/195;23.6%)、40(140/185;75.5%)和80(63/85;74.1%)mg/kg/天的胎儿中发现腭裂。高剂量时多余肋骨出现剂量相关增加,无脑儿和脐疝出现频率较低。这项研究表明,敌菌丹在CD-1小鼠中具有致畸性,其剂量远低于引起母体毒性的剂量。