The modifying effect of folinic acid on diphenylhydantoin-induced teratogenicity in mice

Abstract

To test the alleged association between diphenylhydantoin sodium (DPH) teratogenicity in animals and folic acid antagonism, inseminated female mice were treated ip with 50 mg/kg of DPH, a dose reported to be teratogenic in mice. They were given concurrent im doses of folinic acid (FA) of 1, 10, 20, 30, 40 and 100 mg/kg. The incidence of cleft palate in each group was determined. Statistical evaluation of the data demonstrated marked litter variance and a nonlinear modifying response. The incidence of cleft palate was not significantly different between groups receiving DPH alone and groups receiving DPH plus high doses (40–100 mg/kg) of FA or low doses (20 mg/kg) of FA. However, there was a significant difference ( p < 0.05) in the incidence of cleft palate between the groups receiving the high and low doses of FA. The data suggest that the various doses of FA, given concurrently with DPH, offer no significant protection against the development of cleft palate in mice, but do influence its incidence in a nonlinear fashion.