Developmental effects of phenytoin may differ depending on sex of offspring.

Phenytoin (sodium salt), a developmental neurotoxicant, was administered orally by gavage (50-150 mg/kg) to pregnant rats on days 7-18 of gestation. Various developmental and behavioral indices were evaluated. Results indicated that phenytoin produced decreases in maternal and pup body weight gains, pup hindbrain, and F1 adult forebrain, whole brain, and cerebellar weights. Behavioral/developmental effects included performance deficits in a modified Morris water maze assay, in air righting and auditory startle responses, and increases in locomotor activity, accelerated eye opening, incisor eruption, negative geotaxis, and olfactory orientation. Female offspring appeared to be more severely affected when measuring incisor eruption, negative geotaxis, air righting, reactivity, and locomotor and maze activity. Males appeared to be more affected when measuring eye opening, olfactory orientation, and decreases in startle response. This study suggests that prenatal phenytoin exposure may result in developmental changes and behavioral deficits that may differ depending on the sex of the offspring.