Toxicity study of the new glucocorticosteroid budesonide in rats

16 alpha,17 alpha-Butylidenedioxy-11 beta,21-dihydroxypregna-1,4-diene-3,20- dione (budesonide) was administered subcutaneously to male and female Wistar rats at the doses 0.01, 0.1 and 5 micrograms/kg/d (10 animals/group), and 5, 20 and 80 micrograms/kg/d (15 animals/group) for 26 weeks in two separate studies. A dose-dependent decrease in body weight gain in the groups given 5, 20 and 80 micrograms/kg/d compared with the control group was noted as well as a dose-related reduction in food intake in males receiving 20 or 80 micrograms/kg/d. Increased values for packed cell volume, hemoglobin concentration and erythrocyte counts were found for both sexes at the dose levels 20 and 80 micrograms/kg/d. Also a marked decrease in the number of lymphocytes was seen for both sexes at 80 micrograms/kg/d, and for females also at 20 micrograms/kg/d. Pathological changes associated with treatment with budesonide were found in the liver--panacinar hepatocytic fine vacuolation in females receiving 80 micrograms/kg/d; cervical lymph nodes--low numbers of small lymphocytes in both males and females receiving 20 or 80 micrograms/kg/d; mesenteric lymph nodes--low numbers of small lymphocytes in females receiving 20 or 80 micrograms/kg/d; thymus--low numbers of small lymphocytes in females receiving 80 micrograms/kg/d; mammary glands--acinar hyperplasia and secretion in both sexes receiving 20 and 80 micrograms/kg/d; uterus--dilation of the lumen in females receiving 20 or 80 micrograms/kg/d. Treatment with budesonide at doses of 5 micrograms/kg/d and below was without effect upon the morphology.