Study on toxicity of halopredone acetate. (III). Chronic toxicity study in rats

Chronic toxicity study of halopredone acetate (THS-201), a synthetic corticosteroid, was carried out using Jcl : Wistar rats. THS-201 was subcutaneously administered to the rat in doses of 0.02, 0.1, 0.5 and 2.5mg/kg/day, with the periods for administration and recovery being 12 and 2 months, respectively. In the group of THS-201 2.5 mg/kg, the below findings were observed :thinning of lumbar hair, suppression in body weight gain, decrease of food consumption in both sexes and decrease of water consumption in male. The lesions to lymphatic system were indicated by the examinations of hemogram, organ weight and histopathology. A few changes in urinary and biochemical values were seen, and foreign body granuloma was observed in the injected subcutis. After 2 month-recovery period, above-mentioned findings almost disappeared. In the group of THS-201 0.5mg/kg, some of the changes were noted slightly and disappeared after the recovery period. IN the groups of THS-201 0.1 and 0.02mg/kg, any toxic changes attrib-utable to THS-201 were not observed. It was concluded that the non-toxic does and the defined toxic dose of THS-201 in this study were 0.1 and 0.5 mg/kg/day, respectively.