[Studies on toxicity of hydrocortisone 17-butyrate 21-propionate -4. Chronic toxicity in rats by subcutaneous administration (author's transl)].
Chronic toxicity of hydrocortisone 17-butyrate 21-propionate (HBP), a new synthetic corticosteroid, was studied in rats. HBP was subcutaneously injected to rats as the daily doses of 0.001, 0.01, 0.01, 1.0 and 3.0 mg/kg for 6 months, and the following recovery test was carried out for 4 weeks. Hydrocortisone 17-butyrate (HB) and betamethasone 17-valerate (BV) were used as the reference drugs at the doses of 0.1, 1.0 and 3.0 mg/kg. The suppression of body weight gain by the administration of HBP was observed at the doses more than 1.0 mg/kg in male and more than 0.1 mg/kg in female, and the dead animals were sent at the highest dose of HB and BV. Mainly at the doses more than 0.1 mg/kg HBP induced the dose-dependent symptoms such as decrease in the number of white blood cells and total protein level in serum, and increase in total cholesterol, GOT and GPT level in serum, and atrophic changes of adrenals, lymphatic tissues, skin and subsexual organs. No usual abnormality was recognized at the doses less than 0.01 mg/kg of HBP. These symptoms were more toxic in male, and the strength of toxicity was in the order of BV greater than HB greater than HBP. Many of these findings have known as common effects of corticosteroids. The changes observed in this study were almost recovered after withdrawal of HBP at the doses less than 0.1 mg/kg. As the result, it was suggested that the maximum non-toxic dose of HBP was 0.001 mg/kg.
D000287:Administration, Topical; D000311:Adrenal Glands / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000633:toxicity; D007279:Injections, Subcutaneous; D007958:Leukocyte Count; D008208:Lymphatic System / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D012867:Skin / Q000473:pathology
D000893:Anti-Inflammatory Agents; C033014:hydrocortisone 17-butyrate 21-propionate; D006854:Hydrocortisone