偶氮四唑二胍的急性毒性实验研究

Experimental study on acute toxicity of Guanidinium Azotetrazolate

目的了解偶氮四唑二胍(GZT)的急性经口毒性及皮肤、黏膜的刺激性,为其毒性分级和标签管理提供依据。方法急性经口毒性试验选择SPF级健康成年SD大鼠50只,雌雄各25只,随机分为5组:1 000、1 414、2 000、2 828、4 000 mg/kg,每组10只。禁食后按体重一次灌胃染毒,观察染毒后大鼠的死亡情况和毒性反应,按寇氏法求GZT经口半数致死量(LD_(50))和LD_(50)的95%可信限(95%CI),按急性毒性分级标准评定GZT毒性大小。急性皮肤刺激和眼刺激试验选择健康成年日本大耳白兔8只,经皮肤及黏膜途径给予GZT原药,观察毒性反应并评分,根据各观察时点动物的刺激反应总分均值,判定GZT对皮肤、眼刺激作用的有无及强度。结果 GZT的经口LD_(50)为2 148 mg/kg,95%CI:1 876～2 460 mg/kg。GZT皮肤刺激性最高总积分平均值为1.6,眼刺激性最高总积分平均值为15。结论 GZT对大鼠的急性经口毒性为低毒,对白兔皮肤有轻度刺激性,对白兔眼睛有中度刺激性,刺激可逆。

To provide evidence for toxicity classification and label management by studying the acute oral toxicity,skin irritation and mucosal irritation of guanidinium azotetrazolate(GZT).[Methods]Acute oral toxicity test:50 healthy adult SD SPF rats,half male and half female,were randomly divided into five groups:1 000 mg/kg,1 414 mg/kg,2 000 mg/kg,2 828 mg/kg and 4 000 mg/kg,10 rats in each group.After fasting,the rats were exposed to arsenic by oral perfusion at weight dose,the death and toxicity of rats were observed and the lethal median dose(LD50)and the 95%confidence limits of LD50 were determined according to the method of Karber.The acute toxicity of GZT was assessed according to the acute toxicity grading standard.Acute skin irritation and eye irritation test:eight healthy adult Japanese white rabbits were selected.GZT was given through the skin and mucous membrane,and the toxicity and score were observed.According to the mean value of the total score of the stimulus response at each observation point,the intensity of the irritation of the subjects on the skin and eye was determined.[Results]Orally LD50 of GZT was 2 148 mg/kg and 95%confidence limit was 1 876-2 460 mg/kg.The skin irritation total average score of GZT was 1.6,and mean value of total maximum score of eye irritation was 15.[Conclusion]The acute oral toxicity of GZT is low to the rats,and it has a mild irritation to the white rabbit skin,moderate irritation to the white rabbit eyes and reversible stimulation.