三聚氰胺与三聚氰酸对小鼠的联合急性毒性

The combined acute oral toxicity of melamine and cyanuric acid in mice

目的:研究不同比例的三聚氰胺(melamine,M)与三聚氰酸(cyanuric acid,C)联合给药对小鼠的联合急性毒性。方法:选择SPF级昆明种小鼠240只,随机分为20组,每组12只,雌雄各半。采用寇氏法研究三聚氰胺与三聚氰酸(M+C)对小鼠的联合急性毒性,M+C按1∶1、2∶1、1∶2三种比例混合经口一次性灌胃给药。每种比例设立6个剂量组即109、173、274、435、689和1092mg/kg,灌胃容量为0.02mL/g。并设溶剂对照组(给予等体积的玉米油),另设空白组。动物给药后记录生长情况、死亡情况、死亡动物体质量与肾脏质量,连续观察14d,计算半数致死剂量(median lethal dose,LD)。第15天将存活动物全部脱臼处死,解50剖观察,记录动物体质量与肾脏质量。结果:M+C(1∶1)组,雄鼠LD为274mg/kg、雌鼠LD为401mg/kg;M+C(2∶1)组,雄鼠5050LD值为401mg/kg、雌鼠LD值为546mg/kg;M+C(1∶2)组,雄鼠LD值为344mg/kg、雌鼠LD值为589mg/kg。M+C3种比例混合50505050物经口灌胃,剂量为1092mg/kg时,动物均死亡;剂量低于173mg/kg时,各组动物均无死亡。M+C各给药试验组,小鼠肾脏均发生病变,肾脏不同程度膨胀,表面可见斑点,肾脏脏器系数值大于两个对照组(P<0.05)。结论:三聚氰胺与三聚氰酸混合物在1∶1比例下,经口毒性较大,对雄鼠的毒性大于雌鼠,可引起肾毒性。与单独三聚氰胺或三聚氰酸毒性相比,M+C联合毒性大。

OBJECTIVE： To study the combined acute toxicity of different concentrations of melamine and cyanuric acid （M＋C） in KM mice, and calculate the corresponding median lethal dose （LD,0）. METHODS： 240 SPF Kunming mice were randomly divided into 20 groups, each group 12 mice, male and female in half. Three proportions of melamine and cyanuric acid（1 ： 1, 2 ： 1 and 1 ： 2） were infused with the spray by single oral injection into mice, and Karber has used to explore the combined acute toxicity of M＋C mixture. Six dose groups were treated in each proportion, for 109, 173, 274, 435, 689 and 1092 mg/kg same volume of corn oil was as the solvent control group , respectively, and orally capacity was 0.02 mL/g. The and the blank control group at the same time. The growing states, deaths, body-weight and kidney viscera coefficient of mice were all observed for 14 days after administration, and median lethal dose was calculated. The mice were cervical dislocation to death in 15 days, and body-weight and kidney-weight of mice were checked. RESULTS： The median lethal dose of M＋C（1 ： 1） in male mice was 274 mg/kg , and in female mice 401 mg/kg. The median lethal dose of M＋C（2 ： 1） in male mice was 401 mg/kg, and in female mice 546 mg/kg. The median lethal dose of M＋C （1 ： 2） in male mice was 344 mg/kg , and in female mice 589 mg/kg. The lethal dose of M＋C mixture was 1 092 mg/kg, and the non-fatal dose was 173 mg/kg. Kidney damage was observed in experimental animals, which was swelled and some spot was seen. CONCLUSION： More toxicity was found with the mixture of M＋C in 1 ： 1 ratio, and more in male mice than female mice. M＋C mixture could induce renal toxicity. The combined toxicity of melamine and cyanuric acid was more than either alone. [KEY WORDS1 melamine; cyanuric acid; nephrotoxicity; combined toxicity