[Study on toxicity of halopredone acetate. (II). Subacute toxicity study in rats]

Halopredone acetate (THS-201), a synthetic corticosteroid, is expected to be used clinically for intra-articular injection because of its long-lasting activity in the synovial bursa. Subacute toxicity study was carried out on THS-201 by using Jcl: Wistar rats. THS-201 was subcutaneously administered to the rat in doses of 0.1, 0.5, 2.5 and 12.5 mg/kg/day, with the periods for administration and recovery being 3 and 2 months, respectively. Methylprednisolone acetate (MPA) was used for the positive control in dose of 0.5 mg/kg/day. In the group of THS-201 12.5 mg/kg, the below findings were observed: thinning of lumbar hair, swelling of injection site, suppression in body weight gain and decrease of food consumption. The lesions to lymphatic system were indicated by the examinations of peripheral blood, autopsy and histopathology. Slight changes in erythrocytic and biochemical values were seen, and foreign body granuloma was observed in injected subcutis. These findings, exception for lesion of injection site, were almost recovered after the 2 month-recovery period. In the group of THS-201 2.5 mg/kg, some of the changes were noted slightly. In the groups of THS-201 0.5 and 0.1 mg/kg, any toxic changes attributable to THS-201 were not observed. On the other hand, in the group of MPA 0.5 mg/kg, similar findings noted in THS-201 12.5 mg/kg group were observed, but these changes were recovered almost completely at the end of the 2 month-recovery period. It was concluded that the non-toxic dose and the defined toxic dose of THS-201 in this study were 0.5 and 2.5 mg/kg/day, respectively.