Embryotoxicity of the folate antagonist methotrexate in rats and rabbits

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abnormalities, Drug-Induced*
  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Fetal Death / chemically induced*
  • Fetal Resorption / chemically induced
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Methotrexate / administration & dosage
  • Methotrexate / toxicity*
  • Pregnancy
  • Rabbits
  • Rats
  • Species Specificity


  • Methotrexate