Buttar H S, Dupuis I, Khera K S
Toxicology. 1978 Feb;9(1-2):155-64. doi: 10.1016/0300-483x(78)90040-9.
The fetotoxic potential of dimethadione was studied in rats given single daily oral dosages of 0, 54, 433 or 541 mg/kg on days 1--21 or 6--15 of gestation. No maternal toxicity was observed following treatment on days 6--15. When administered from days 1 to 21 only the highest dose (541 mg/kg) produced a significant reduction in maternal body weight gain. Dimethadione caused a dose-related decrease in fetal weight and an increased incidence of umbilical hernia, ecchymoses and subcutaneous edema. There were also increased incidences of non-specific skeleton defects which consisted of unilateral or bilateral wavy ribs, additional ribs (14th rib, uni- and bilateral), retarded ossification of calvaria and a wide variety of sternal defects. Specific defects were bent radius and ulna, and bent tibia and fibula which increased with increasing dosages of dimethadione. Fetal mortality and incidence of skeletal anomalies were higher when the treatment was given on days 1--21 of gestation than on days 6--15 of pregnancy.
在妊娠第1至21天或第6至15天，给大鼠每日口服0、54、433或541mg/kg的二甲双酮，研究其对胎儿的毒性潜力。在第6至15天给药后未观察到母体毒性。当从第1天至21天给药时，只有最高剂量（541mg/kg）导致母体体重增加显著降低。二甲双酮导致胎儿体重呈剂量相关下降，脐疝、瘀斑和皮下水肿的发生率增加。非特异性骨骼缺陷的发生率也增加，包括单侧或双侧波浪状肋骨、额外肋骨（第14肋，单侧和双侧）、颅骨骨化延迟以及多种胸骨缺陷。特异性缺陷为桡骨和尺骨弯曲以及胫骨和腓骨弯曲，随着二甲双酮剂量增加而增加。在妊娠第1至21天给药时，胎儿死亡率和骨骼异常发生率高于妊娠第6至15天。
