Kirk H D, Berdasco N M, Breslin W J, Hanley T R
Toxicology Research Laboratory, Dow Chemical Company, Midland, Michigan 48674, USA.
Fundam Appl Toxicol. 1995 Nov;28(1):18-26. doi: 10.1006/faat.1995.1141.
1,2-Dichloropropane (PDC) was evaluated for its potential to cause embryonal/fetal toxicity and teratogenicity in pregnant rats and rabbits. PDC was administered via oral gavage at dose levels of 0, 10, 30, or 125 mg/kg/day on Days 6 through 15 of gestation (rats) or 0, 15, 50, or 150 mg/kg/day on gestation Days 7 through 19 (rabbits). Fetuses were examined on Gestation Day 20 (rats) or Day 28 (rabbits). Maternal toxicity was observed in both rats and rabbits at the high dose levels. Rats given 125 mg/kg/day of PDC showed clinical signs of toxicity and decreased body weight and body weight gain. Rabbits given 150 mg/kg/day PDC showed changes in hematologic parameters and decreased body weight gain. Although maternal toxicity was apparent, no indication of teratogenicity was observed in rat or rabbit fetuses at any dose level. Significant increases in the incidence of delayed ossification of skull bones, considered secondary to decreased maternal body weight gain, were observed in rats given 125 mg/kg/day and in rabbits given 150 mg/kg/day. No maternal or developmental effects were observed in rats given 10 or 30 mg/kg/day or in rabbits given 15 or 50 mg/kg/day of PDC. Based on the results of these studies the maternal and developmental NOELs in rats and rabbits were 30 and 50 mg/kg/day, respectively.
对1,2 - 二氯丙烷（PDC）在妊娠大鼠和家兔中引发胚胎/胎儿毒性和致畸性的可能性进行了评估。在妊娠第6至15天（大鼠），以0、10、30或125毫克/千克/天的剂量水平经口灌胃给予PDC；在妊娠第7至19天（家兔），剂量水平为0、15、50或150毫克/千克/天。在妊娠第20天（大鼠）或第28天（家兔）检查胎儿。在高剂量水平下，大鼠和家兔均观察到母体毒性。给予125毫克/千克/天PDC的大鼠出现毒性临床体征，体重和体重增加减少。给予150毫克/千克/天PDC的家兔血液学参数发生变化，体重增加减少。尽管母体毒性明显，但在任何剂量水平下，大鼠或家兔胎儿均未观察到致畸迹象。在给予125毫克/千克/天的大鼠和给予150毫克/千克/天的家兔中，观察到颅骨延迟骨化发生率显著增加，这被认为是由于母体体重增加减少所致。给予10或30毫克/千克/天PDC的大鼠以及给予15或50毫克/千克/天PDC的家兔未观察到母体或发育影响。基于这些研究结果，大鼠和家兔的母体和发育无观察到有害作用水平分别为30和50毫克/千克/天。
