Comparative study of the teratogenicity of phenobarbitone, diphenylhydantoin and carbamazepine in mice

Three selected anticonvulsants, phenobarbitone (PHB), diphenylhydantoin (DPH) and carbamazepine (CAA) were examined for embryotoxic and teratogenic activity in albino mice. After oral treatment of the dams during the period of organogenesis (days 6-15 of gestation) with both PHB and DPH in doses causing marked symptoms and signs of toxicity (40 and 170 mg/kg/day respectively), an abnormally high incidence of cleft palate was observed in the foetuses (4.3% and 9.3% resp.). In a cumulative control group of foetuses, the incidence of this particular malformation was only 0.13%. No significant change in the malformation rate was seen after the administration of CAA in doses up to 250 mg/kg/day. Slight to moderate retardation of foetal growth was noted after treatment with DPH and CAA, but only at the higer and toxic dose levels. DPH also increased the incidence of early embryonic deaths (deciduomata).