N-脒基脲二硝酰铵盐的急性毒性试验研究

Study on acute toxicity of N-Guanylureadinitramide

目的研究N-脒基脲二硝酰铵盐(FOX-12)的急性毒性。方法急性经口毒性试验采用1 000、1 495、2 236、3 344、5 000 mg/kg 5个剂量组进行试验,每组10只SD大鼠,雌雄各5只,染毒后连续观察14天;7只日本大耳白兔分别进行皮肤刺激和眼刺激试验,皮肤刺激试验染毒后观察72 h,眼刺激试验染毒后观察7天;40只白化豚鼠进行皮肤致敏试验,分别为染毒组、阴性对照组和阳性对照组。激发24 h和48 h后分别观察对照组和试验组局部皮肤反应。结果在14天观察期内,急性经口毒性试验染毒后第7天雌性大鼠体重差异有统计学意义(P<0.01),雌性大鼠死亡7只,雄性大鼠死亡12只,雌、雄性经口LD_(50)分别为3 480.346和2 326.976 mg/kg,合并性别的LD_(50)为2 845.818 mg/kg;皮肤刺激1、24、48和72 h,4只白兔均未出现红斑与焦痂,且皮肤无水肿;眼刺激试验染毒1 h后3只白兔眼睛出现明显刺激症状,到染毒后第7天症状全部消失;皮肤致敏试验激发接触后24 h和48 h,豚鼠皮肤均未出现异常。结论 FOX-12对雌、雄性大鼠急性经口属低毒,对白兔无皮肤刺激性,对眼睛具有轻度刺激性,且具有可逆性,对豚鼠皮肤不具有致敏性。

Objective To study the acute toxicity of N-Guanylureadinitramide(FOX-12).Methods Five dose groups of 1000,1495,2236,3344 and 5000 mg/kg were administrated for acute oral toxicity test.10 SD rats in each group,half male and half female,and they were observed for 14 days after exposure.Seven Japanese white rabbits were used for skin irritation and eye irritation,and the observation periods were 72 hours for skin irritation and 7 days for eye irritation,respectively.40 albino guinea pigs were subjected to skin sensitization test,including the exposure group,negative control group and positive control group.Local skin reactions were observed after 24 hours and 48 hours.Results During the observation period of 14 days,there was a statistically significant difference in body weight of female rats on 7th day after exposure(P<0.01).7 female rats and 12 male rats died in acute oral toxicity test.The LD 50 orally of female and male rats were 3480.346 and 2326.976 mg/kg,respectively.The LD 50 of the combined sex was 2845.818 mg/kg.After 1,24,48 and 72 hours of skin irritation,there were no erythema and eschar in all the four rabbits,and no skin edema.After 1 hour of exposure,3 white rabbits showed obvious eye irritation symptoms in eye stimulation test,and all symptoms disappeared on the 7th day after exposure.After 24 hours and 48 hours of skin sensitization test,no abnormal skin was observed in guinea pigs.Conclusion FOX-12 is low toxicity to male and female rats.No skin irritation and mild eyes irritation were observed to white rabbits.No sensitization was seen to guinea pig skin.