Teratogenicity of diphenylhydantoin in the New Zealand white rabbit

Abstract

Abstract The teratogenic potential of diphenylhydantoin sodium (DPH) was investigated in the rabbit after oral intubation of 0 (Control), 25, 50, 75, 100, and 150 mg/kg/day from days 7–18 of gestation. Except for reduced maternal weight gains at the two higher dosages, no other obvious pharmacological or toxic effects were noted in treated rabbits. Dose‐response‐related increases in the resorption and malformation rates were observed. Four litters (one of 14 litters with viable fetuses at 75 mg/kg/day and three of eight litters with viable fetuses at 100 mg/kg/day) exhibited a similar pattern of multiple malformations that included some or all of the following defects: open eyes, cleft palate, and limb abnormalities that included shortened and curved long bones, pes caves, syndactyly, and ossification defects of the phalanges. Dosages of 150 mg/kg/day produced nearly complete resorption, which may have masked the teratogenic response to the drug.