Acute and Subacute Toxicity Studies of Water Soluble Dimethyl Dimethoxy Biphenylate Derivative in Rats

수용성 DDB유도체의 주사제 개발을 위한 급성독성 및 아급성독성시험연구

The acute and subacute toxicity of water soluble dimethyl dimethoxy biphenylate derivative (new DDB), hepatitis therapeutics, were investigated in SD rats. In the acute toxicity study, body weights and clinical signs were observed for 7 days after the intravenous injection of new DDB at doses of 140, 182, 236, 307 and 400 mg/kg(r=1.3). Death. Severe convulsion, tremor and decrease motor activity were observed in almost treated groups (except the 140 mg/kg treated group). Changes of body weight in treated groups were not significantly different from control group. Autopsy of survived animals revealed no abnormal gross findings related to new DDB. As a results, the $LD_{50}$ values of new DDB were 244.1 mg/kg for male and 232.5 mg/kg for female. In subacute toxicity study, body weights and clinical signs were observed after intravenous injection of new DDB at doses of 57, 75 and 100 mg/kg/day for 28 days. Death, decrease motor activity and tremor were observed above 75 mg/kg treated groups. Statistically significant changes were observed in hematological and biochemical parameters of new DDB-treated groups; however, these changes were within normal range and had no relationship with dosage. Several abnormal findings were observed in microscopic examination of tissue; however, these findings were not caused by new DDB but environmental factor. The no toxic dose level of new DDB were estimated to be 57 mg/kg/day in this study.