Teratogenicity study of the new glucocorticosteroid budesonide in rabbits

16 alpha,17 alpha-Butylidenedioxy-11 beta,21-dihydroxy-pregna-1,4-diene-3,20-dione (budesonide), a newly developed glucocorticosteroid, was administered subcutaneously to pregnant rabbits at doses of 0.01, 0.06 and 0.29 mumol/kg during the organogenetic period. As a reference compound the glucocorticosteroid fluocinolone acetonide, at the dose 0.28 mumol/kg, was used. In the group given 0.06 mumol/kg 2 dams out of 15 aborted. All animals receiving 0.29 mumol/kg aborted. All dams receiving fluocinolone acetonide aborted. The food consumption was reduced in all groups given budesonide. The body weight change was dose-dependently reduced for the groups receiving budesonide. The group receiving fluocinolone acetonide also showed a negative body weight change compared with the control group. The affected litter parameters were: reduced litter and fetal weight in the groups receiving 0.01 and 0.06 mumol/kg of budesonide, indicating intrauterine growth retardation. Furthermore, the frequency of fetal abnormalities, mainly skeletal anomalies, was significantly increased in the group receiving 0.06 mumol/kg of budesonide. The anomalies seen were mostly different kinds of delayed development of the bones in the skull and at the vertebra. A direct teratogenic effect cannot be excluded but severe maternal toxic reactions may have contributed to the pregnancy outcome.