Acute Toxicity Study of DA-5018, A Non-narcotic Analgesic Agent

비 마약성 진통제 DA-5018의 급성독성시험

Intravenous and oral acute toxicity tests in ICR mice and SD rats and percutaneous acute toxicity tests in SD rats and NZW rabbits were conducted to evaluate the toxicity of DA-5018 and DA-5018 cream, respectively Clinical signs observed in mice and rats after the administration of DA-5018 were similar regardless of administration route. The observed clinical signs were jumping, wild running, lacrimation, ataxia, reddening of extremities and ears, ventral or lateral recumbency, respiratory distress, cyanosis, convulsion and death. Pulmonary enlargement and hemorrhage were observed in the animals died immediately after the dosing of DA-5018. At terminal necropsy, pulmonary enlargement and hemorrhage, corneal opacity and focal scabbing and depilation around nose were seen. LD$_{50}$ Values of DA-5018 are 11.5 mg/kg (mice, male), 12.6 mg/kg (mice, female), 88.3 mg/kg (rat, male) and 73.2 mg/kg (rat, female) in oral toxicity tests and 11.0 mg/kg (mice, male), 18.7 mg/kg (mice, female), 0.12 mg/kg (rat, male) and 0.32 mg/kg (rat, female) in i.v. toxicity tests. In the percutaneous acute toxicity tests of DA-5018 cream, no deaths occured in all the tested groups during 14-day observation period. There were also no abnormalities in the general conditions, body weight changes and on necropsy findings in all groups. LD$_{50}$ values of 0.1 ~0.9% DA-5018 creams in male and female rats and rabbits are >2000 mg/kg./kg.