Teratogenicity of methotrexate in mice

The folic acid analogue methotrexate (MTX) was evaluated for its embryotoxic potential in ICR mice on day 10 (stage 18) of gestation. No malformations were produced at doses shown to be embryotoxic in humans, rats, rhesus monkeys, and rabbits (0.3–10 mg/kg), although a significant increase in resorption rate was observed in litters treated with 10 mg/kg. Doses between the LD10 and the LD50 (25 and 50 mg/kg) produced a parallel increase in intrauterine death and congenital defects.