[Studies on toxicity of clobetasone-17-butyrate (II)--chronic toxicity in rats (author's transl)].

Chronic toxicity of clobetasone-17-butyrate, an anti-inflammatory corticosteroid, was investigated in rats. Subcutaneous administration with the drug at dose of 0.003, 0.01 and 0.03 mg/kg/day for three and six months induced no significant changes in the rats. At 0.1 and 0.3 mg/kg/day, however, some dose-dependent symptoms such as suppression of body weight gain, emaciation, regressive changes in adrenals, lymphatic and hematopoietic tissues, decrease in circulating white blood cell and lymphocyte counts, which have been known as toxic effects of synthetic corticosteroids, were induced. The results indicates that the maximum no-toxic dose of clobetasone-17 butyrate was 0.03 mg/kg/day on this experimental condition. In the recovery test for two months no significant differences in the treated rats from controls were found, suggesting that the toxic effects were reversible in the animals treated at 0.3 mg/kg/day and lower than that.

[Studies on toxicity of clobetasone-17-butyrate (I)--acute toxicity in mice and rats and subacute toxicity in rats (author's transl)].

Acute and subacute toxicities of clobetasone-17-butyrate, a new anti-inflammatory corticosteroid, were studied in mice and rats. In the acute toxicity tests intraperitoneal LD50 values of the drug were estimated to be around 5 g/kg for both sexes of mice, 1.51 g/kg for male and 1.66 g/kg for female rats. Subcutaneous and oral administration induced no fatal cases at dose of 3.6 (mice, s.c.), 2.6 (rats, s.c.) and 6.0 g/kg (mice and rats, p.o.). As for the toxic signs in both mice and rats after the i.p. and s.c. administrations, emaciation was marked, and atrophy of thymus, spleen and adrenals were observed. No marked symptoms, however, were induced in animals administered orally. In the subacute toxicity tests male and female rats were subcutaneously administered with the drug at daily doses of 0.01, 0.03, 0.1, 1.0, 10 and 100 mg/kg for one month. Dose dependent symptoms such as suppression in body weight gain, emaciation, regressive changes in adrenal, lymphatic and hematopoietic tissues, decrease in circulating white blood cell and lymphocyte counts, and increase in total cholesterol level of serum were induced in the rats administered at 0.1 mg/kg/day and more than that, indicating that the maximum nontoxic dose in this experimental condition was 0.03 mg/kg/day. In recovery tests it was observed that the rats, which had been administered with the drug at 1.0 mg/kg/day for one month, were almost normal two months after the final administration.