[Study on toxicity of halopredone acetate. (I) Acute toxicity study in mice and rats]

Since halopredone acetate (THS-201), a synthetic corticosteroid, is expected to be used clinically for intra-articular injections because of its long-lasting activity in the synovial bursa, its acute toxicity was compared with that of triamsinolone acetonide (TA) and methylprednisolone acetate (MPA). The test animals were Jcl: ICR mice and Jcl: Wistar rats, and drugs were administered orally, intraperitoneally and subcutaneously. The LD50 values of THS-201 both in mice and rats were estimated more than 5000 mg/kg at each route, and these are for above larger than those of TA or MPA. Moreover, in oral and subcutaneous administration of THS-201, no severe toxic signs were observed either in mice or in rats. In intraperitoneal injection, a few of mice and rats died after showing several clinical signs and suppression of body weight gain, and their autopsy revealed atrophy of thymus, spleen and adrenal, induction of infection and hemorrhage in digestive tract. On the other hand, the mice and rats administered TA or MPA revealed the severe toxic signs such as loss of hair gloss, marked emaciation, decrease in spontaneous movement, anemia, bloated face, decrease or suppression of body weight gain, atrophy of thymus, spleen and adrenal, severe induction of infection and lesions in digestive tracts. Accordingly, it is concluded that the acute toxicity of THS-201 in mice and rats was lower than that of TA or MPA.