Jordan R L, Wilson J G, Schumacher H J
Teratology. 1977 Feb;15(1):73-9. doi: 10.1002/tera.1420150110.
The prenatal effects of methotrexate (MTX) in rats and rabbits were assessed. It was found highly embryotoxic in postimplantation rat embryos; 0.3 mg/kg ip or less caused nearly total embryolethality with slight teratogenicity. Rabbit embryos were far more resistant to small doses of MTX than rats, but 19.2 mg/kg iv, when given during days 10 to 15 of gestation, produced little death and a constant spectrum of malformation in a high percentage of offspring. Cleft palate, skull defects, and severe fore- and hindlimb dysplasias, occurred with a high degree of regularity and were strongly dose and developmental-stage specific.
评估了甲氨蝶呤（MTX）对大鼠和兔子的产前影响。发现其对植入后大鼠胚胎具有高度胚胎毒性；腹腔注射0.3mg/kg或更低剂量几乎导致胚胎全部死亡，且有轻微致畸性。兔子胚胎对小剂量MTX的耐受性远高于大鼠，但在妊娠第10至15天静脉注射19.2mg/kg时，很少导致死亡，且在高比例后代中产生一系列持续的畸形。腭裂、颅骨缺陷以及严重的前肢和后肢发育异常出现的规律性很高，且具有强烈的剂量和发育阶段特异性。
