Gray L E, Rogers J M, Kavlock R J, Ostby J S, Ferrell J M, Gray K L
Teratog Carcinog Mutagen. 1986;6(1):33-43. doi: 10.1002/tcm.1770060105.
The present study is an evaluation of the developmental toxicity of dinocap in three rodent species using an in vivo teratology screen. Our protocol uses postnatal viability, weight gain, and morphological and behavioral development through weaning to assess the developmental toxicity of compounds. Dinocap administered orally on days 7 to 16 of gestation to the CD-1 mouse resulted in increased postnatal mortality at 25 mg/kg/d (80% in block 1 and 40% in block 2). Many of the treated pups that died during the neonatal period were "ballooned" and had cleft palates. Although there was no treatment related mortality in the 12 mg/kg/d dosage group, 6% (14/226) of these mice and 24% (23/96) of the survivors from the 25 mg/kg/d dosage group displayed torticollis (a twisting of the neck resulting in an abnormal tilting of the head). These tilted-head mice held the head and forepart of the body tilted constantly to one side, both when resting and walking. The tilt was in either direction but was always constant for a given animal; in different mice, the angle varied considerably from almost 0 to 30 degrees. Some mice circled repeatedly in one direction in the home cage, others bobbed their heads and did back-flips, while others rolled over, always rolling in the same direction. In the hamster, developmental toxicity was seen at (100 and 200 mg/kg/d) or near (50 mg/kg/d) maternally toxic doses but no behavioral alterations were noted and none of the pups were ballooned.
本研究使用体内致畸学筛选方法评估了敌螨普对三种啮齿动物的发育毒性。我们的实验方案通过断奶后的存活能力、体重增加以及形态和行为发育来评估化合物的发育毒性。在妊娠第7至16天对CD-1小鼠经口给予敌螨普,剂量为25mg/kg/d时导致出生后死亡率增加(第1组为80%,第2组为40%)。许多在新生儿期死亡的受试幼崽出现“气球样”外观并有腭裂。虽然12mg/kg/d剂量组没有与治疗相关的死亡,但该组6%(14/226)的小鼠以及25mg/kg/d剂量组24%(23/96)的存活小鼠出现斜颈(颈部扭曲导致头部异常倾斜)。这些斜颈小鼠在休息和行走时,头部和身体前部持续向一侧倾斜。倾斜方向不定,但对某一只动物而言是固定的;不同小鼠的倾斜角度差异很大,从几乎0度到30度不等。一些小鼠在饲养笼中沿一个方向反复转圈,另一些小鼠点头并做后空翻,还有一些小鼠翻滚,且总是朝同一方向翻滚。在仓鼠中,在母体毒性剂量(100和200mg/kg/d)或接近该剂量(50mg/kg/d)时观察到发育毒性,但未发现行为改变,且没有幼崽出现“气球样”外观。