SD大鼠28 d重复剂量经口毒性试验生物学指标实验室历史对照值研究

Study on the laboratory historical control values of biological indicators in SD rats with 28-day repeated dose oral toxicity tests

目的建立28 d重复剂量经口毒性试验中SD大鼠生物学指标的实验室历史对照值。方法收集10批次28 d重复剂量经口毒性试验中,对照组和对照附加组无特定病原体级SD大鼠的体质量、血常规指标、血清生化指标、脏器质量和脏器系数,建立本实验室的历史对照值。结果雌性和雄性SD大鼠体质量均随着周龄的增加而增加(P值均<0.01),各周龄雄性大鼠体质量均高于雌性大鼠(P值均<0.01)。SD大鼠的体质量、血常规与血清生化指标、脏器质量和脏器系数均不同程度地受到周龄和性别的影响;脏器质量与脏器系数受周龄和性别的影响程度不一致。分别按照SD大鼠的周龄和性别建立其体质量、血常规指标、血清生化指标、脏器质量和脏器系数的实验室历史对照值。结论应按照不同的周龄和性别建立SD大鼠生物学指标的实验室对照值;与脏器质量比较,脏器系数更适合作为毒理学安全性评价的观察指标。

Objective To establish the laboratory historical control values for biological indicators in SD rats with 28-day repeated dose oral toxicity tests. Methods The body mass, blood routine indexes, serum biochemical indexes, organ mass and organ coefficient of 10 batches of specific pathogen free SD rats in the control group and the control additional group were collected for 28-day repeated dose oral toxicity tests, and the historical control values was established. Results The body mass of both male and female SD rats increased with the increasing age(all P<0.01). The body mass of male rats was higher than that of female rats each week(all P<0.01). The body mass, blood routine and serum biochemical indexes, organ mass and organ coefficient of SD rats were affected by the age and gender of rats to varying degrees. The effects of age and gender on organ mass and organ coefficient were not consistent. The laboratory historical control values of body mass, blood routine indexes, serum biochemical indexes, organ mass and organ coefficient of SD rats were established according to the age measured in weeks and the gender of rats. Conclusion The laboratory control values of biological indicators of SD rats should be established according to different weekly age and the gender of rats. Organ coefficient is more suitable as an observation index for toxicological safety evaluation compared with organ mass.