Jackson A J, Schumacher H J
Teratology. 1979 Jun;19(3):341-4. doi: 10.1002/tera.1420190310.
The relationship between the teratogenicity of EM12, 2-(2,6-dioxopiperiden-3'-yl) phthalimidine, a stable analogue of thalidomide, and zinc status in the maternal animal was investigated using pregnant rats on a low-zinc diet (1 ppm zinc, days 0--14 gestation) as the experimental model. Previous studies with this compound in rats fed a commercial diet at oral doses up to 250 mg/kg per day for three days and intravenous doses up to 10 mg/kg per day for three days failed to produce "typical" thalidomide malformations. However, when a dose of 150 mg/kg was given intraperitoneally to rats on a low-zinc diet, typical thalidomide malformations occurred with an incidence of 57.5%.
使用低锌饮食(妊娠第0至14天,锌含量为1 ppm)的怀孕大鼠作为实验模型,研究了沙利度胺的稳定类似物EM12(2-(2,6-二氧代哌啶-3'-基)邻苯二甲酰亚胺)的致畸性与母体动物锌状态之间的关系。此前对该化合物进行的研究中,给喂食商业饲料的大鼠口服剂量高达每天250 mg/kg,持续三天,静脉注射剂量高达每天10 mg/kg,持续三天,均未产生“典型”的沙利度胺畸形。然而,当给低锌饮食的大鼠腹腔注射150 mg/kg的剂量时,典型的沙利度胺畸形出现了,发生率为57.5%。