Kavlock R J, Chernoff N, Hanisch R C, Gray J, Rogers E, Gray L E
Toxicology. 1981;21(2):141-50. doi: 10.1016/0300-483x(81)90124-4.
The fetotoxic potential of endrin in the CD rat and CD-1 mouse was investigated. Endrin was administered as a solution in corn oil to groups of pregnant animals by gastric intubation at multiple dose levels throughout the period of organogenesis. The dams were sacrificed prior to term and the fetuses were examined for skeletal and visceral anomalies. In addition, maternal livers and fetuses from rats in each dose level were analyzed for endrin content. In the mouse, endrin caused maternal liver enlargement at a dose of 0.5 mg/kg/day and reduced maternal weight gain at a dose of 1.0 mg/kg/day. Fetal weight and skeletal and visceral maturity were adversely affected at a dose of 1.0 mg/kg/day, but no teratogenic effect or embryo lethality was evident even at a dose level that produced maternal lethality (1.5 mg/kg/day). In the rat, endrin markedly reduced maternal weight at doses above 0.150 mg/kg/day but produced no apparent effects on the fetus. The data suggest that species differences in sensitivity to endrin may in part be due to differences in metabolism. Although endrin levels in rat fetuses at a maximally tolerated dosage level resembled those previously reported for the hamster, relatively less 12-ketoendrin was present, paralleling the change in fetal sensitivity.
研究了异狄氏剂对CD大鼠和CD-1小鼠的胚胎毒性潜力。在整个器官形成期,通过胃插管以玉米油溶液的形式将异狄氏剂给予多组怀孕动物,设置多个剂量水平。在足月前处死母鼠,并检查胎儿的骨骼和内脏异常情况。此外,分析了每个剂量水平的大鼠的母鼠肝脏和胎儿中的异狄氏剂含量。在小鼠中,异狄氏剂在剂量为0.5毫克/千克/天时导致母鼠肝脏肿大,在剂量为1.0毫克/千克/天时降低母鼠体重增加。在剂量为1.0毫克/千克/天时,胎儿体重以及骨骼和内脏成熟度受到不利影响,但即使在产生母鼠致死率的剂量水平(1.5毫克/千克/天)下,也没有明显的致畸作用或胚胎致死性。在大鼠中,异狄氏剂在剂量高于0.150毫克/千克/天时显著降低母鼠体重,但对胎儿没有明显影响。数据表明,对异狄氏剂敏感性的物种差异可能部分归因于代谢差异。尽管在最大耐受剂量水平下大鼠胎儿中的异狄氏剂水平与先前报道的仓鼠相似,但相对较少的12-酮异狄氏剂存在,这与胎儿敏感性的变化平行。