DHPO生殖毒性的毒理学评价

目的研究1，2-二甲基-3-羟基-4-吡啶酮（DHPO）的急性毒性及不同剂量、不同时间的生殖毒性。方法以昆明种近交小鼠为实验对象．首先进行半数致死量（LD50）实验，然后对DHPO低（1／8LD50）、中（1／4LD50）、高（1／2LD50）剂量组染毒小鼠进行精子畸变率观察。结果DHPO染毒小鼠经口LD50为562．34mg／kg.精子畸变实验显示，1／8LD50组、1／4LD50组与阴性对照组比较，在第14．28，35，42，70d观察，差异均无统计学意义（P〉0．05）；1／2LD50组与阴性对照组比较，在第14，28，35d观察．差异均有统计学意义（P〈0．05），而在第42，70d观察，差异无统计学意义（P〉O．05）。结论DHPO的低（1／8LD50）、中（1／4LD50）剂量未显示有生殖毒性，高剂量（1／2LD50）具有一定生殖毒性。但可在42d后恢复。

Primary study about reproductive toxicology of DHPO in mice

Objective To evaluate the acute toxicity and reproductive toxicology of deferiprone(DHPO) under various doses and during different periods.Methods Median lethal dose(LD_(50)) test was performed,then Kun Ming mice were administrated different doses of DHPO to cary out the sperm malformation test under low(1/8 LD_(50)),mid(1/4 LD_(50)),high(1/2 LD_(50)) doses.Results LD_(50) of DHPO was 562.34?mg/kg by gavage on mice.There were no significant differences in 1/8 LD_(50) group and 1/4 LD_(50) group in comparison with negative control group in observations conducted din the 14~(th),28~(th),35~(th),42~(nd),and 70~(th) day(P>0.05);While significant differences appeared between 1/2 LD_(50) group and in negative control group in observations conducted in the 14~(th),28~(th) and 35~(th) day(P<0.05);There were no significant differences between 1/2 LD_(50) group and negative control group in observations conducted in the 42~(nd) day and 70~(th) day(P>0.05).Conclusion There is no evidence to indicate that 1/8 LD_(50),1/4 LD_(50) dose have reproductive toxicology(P>0.05).High dose of DHPO(1/2 LD_(50)) has some degrees of reproductive toxicology,but can recover within 42 days.