Comparative teratogenicity of selected glucocorticoids applied ocularly in mice

Three glucocorticoids (dexamethasone, hydrocortisone, and prednisolone), were ocularly applied to pregnant CD-1 mice on days 10-13 of gestation. The drug concentrations were various multiples of the common therapeutic dose levels and were applied to both eyes in 1 microliter drops five times a day. Eighteen-day fetuses were examined for malformations. A significant increase in the incidence of cleft palate was observed in fetuses treated with each of these glucocorticoids. There appeared to be a dose related effect on cleft palate width among fetuses from both dexamethasone and prednisolone treated dams. The incidence of sex organ anomalies, although lower than the incidence of cleft palate, also showed a positive dose relationship. Analysis of variance was used to compare the teratogenic effects of these glucocorticoids ocularly applied in equipotent anti-inflammatory concentrations. Our results indicate that dexamethasone produces a higher incidence of cleft palate, than either of the other two drugs when given in equipotent concentrations. It appears that the teratogenic potency of these ocularly applied glucocorticoids cannot be predicted on the basis of anti-inflammatory potency.