两种动物品系与方法比较硝酸镧的急性经口毒性  

Comparison study on acute oral toxicity of lanthanum nitrate using two animal strains and methods

作　　者：敬海明[1,2] 张国艳 杨庆[1] 韩高超 张鹏[1] 宁钧宇[1,2] 李国君[1,2] JING Hai-ming;ZHANG Guo-yan;YANG Qing;HAN Gao-chao;ZHANG Peng;NING Jun-yu;LI Guo-jun(Beijing Center for Disease Prevention and Control/Beijing Center of Preventive Medicine Research,Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning,Beijing 100013,China;School of Public Health,Capital Medical University,Beijing 100069,China)

机构地区：[1]北京市疾病预防控制中心/北京市预防医学研究中心,食物中毒诊断溯源技术北京市重点实验室,北京100013 [2]首都医科大学公共卫生学院,北京100069

出　　处：《毒理学杂志》2021年第3期173-178,192,共7页Journal of Toxicology

基　　金：国家重点研发计划(2018YFC1602705,2018YFC1603102,2018YFC1602703)。

摘　　要：目的以近交系C57小鼠与远交系KM小鼠为研究对象,应用霍恩氏(Horn)法与上-下法(up-down procedure,UDP)的改良方案,比较硝酸镧(Ⅲ)六水合物的急性经口毒性。方法参照国内外急性经口毒性试验标准或指南中Horn法与UDP法的设计与计算原理,分别选用90只C57小鼠与KM小鼠(雌雄各半)进行随机分组后,经口灌胃给予预定剂量的硝酸镧(Ⅲ)六水合物水溶液,观察实验动物的中毒表现和死亡情况,计算并比较染毒后1、4、24和48 h以及7和14 d时的半数致死量(LD_(50))。结果两种方法观察期结束后,硝酸镧(Ⅲ)六水合物对C57小鼠与KM小鼠的急性经口毒性LD_(50)均在低毒级别(501~5000 mg/kg·bw),但UDP法的95%可信限范围较广,LD_(50)计算的准确性没有Horn法高。另外,C57小鼠的中毒表现多在4 h内,较KM小鼠(24 h)明显更早,并且动物死亡数量也明显更多,提示C57小鼠的毒性反应更加敏感。并且,同一检测方法下某一小鼠的雄性LD_(50)在各时间点均普遍较低于雌性,存在一定的性别差异。结论两种方法检测所得硝酸镧(Ⅲ)六水合物对C57小鼠与KM小鼠的急性经口毒性等级均为低毒,且存在明显的性别差异(毒性反应雄性>雌性),但C57小鼠相对更敏感,提示在进行其他稀土化合物急性毒性检测与评价以及应急毒性检测需缩短观察时间时或可作为优选品系使用。Objective To compare the acute oral toxicity of lanthanum nitrate(Ⅲ)hexahydrate in inbred C57 mice and outbred KM mice by the improved scheme of Horn and up-and-down procedure(UDP)methods.Methods Ninty C57 mice or KM mice(half male and half female)were randomly divided into two groups according to the design and calculation principles of Horn procedure and UDP method in the domestic standards and foreign guidelines for acute oral toxicity test,and then given predetermined doses of lanthanum nitrate(Ⅲ)solutions by oral gavage.Following exposure,clinical observations and the death time of each animal should be recorded.The median lethal dose(LD_(50))at 1,4,24,48 h,7 and 14 d after exposure were calculated and compared.Results The acute oral toxicity LD_(50) of lanthanum nitrate(Ⅲ)hexahydrate to C57 mice and KM mice were all in the low toxicity level(501~5000 mg/kg·bw),but the 95%confidence limit of UDP method was more greater,and the accuracy was not as high as Horn method.In addition,C57 mice appeared toxicity effects within 4 hours,significantly earlier than KM mice(24 hours),and the number of animals died at the specific time point was also significantly more,suggesting that C57 mice were more sensitive to the toxicity of lanthanum nitrate(Ⅲ).Moreover,the LD_(50) of male mice was generally lower than that of female mice at each time point under the same testing method,indicated that there was a gender difference in the toxicity response.Conclusion The acute oral toxicity of lanthanum nitrate(Ⅲ)hexahydrate detected by Horn and UDP method to C57 and KM mice are all at the low toxicity level,and there is a significant gender difference(toxic reaction male>female),but C57 mice are relatively more sensitive,suggesting that it can be used as an optimal strain for testing and evaluation of other rare-earth compounds and emergency toxicity detection when necessary.

关 键 词：硝酸镧(Ⅲ)六水合物 C57小鼠 KM小鼠 霍恩氏法 上-下法 

分 类 号：R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]