4种急性经口毒性试验方法的比较研究

发布时间：2018-05-04 00:31

本文选题：急性经口毒性 + 固定剂量法　；参考：《环境与职业医学》2015年06期

【摘要】：[目的]通过比较4种急性经口毒性试验方法操作性和结果一致性,分析其在化学品急性毒性评价中的应用价值及其意义。[方法]对3种已知化学物(对苯二胺、对苯二酚、硼酸)分别使用固定剂量法(FDP)、上下增减剂量法(UDP)、急性毒性分类法(ATC)3种替代方法与传统霍恩氏(Horn’s)法进行大鼠急性经口毒性试验。比较各方法判断化学物毒性分类的一致性;并对动物使用、剂量选择、观察指标进行综合分析。[结果]3种化学物分别用4种方法测定得到的全球化学品统一分类和标签系统(GHS)分类结果一致。3种替代方法均采用序贯原则,使用实验动物数量较少,但实验周期更长。FDP法和ATC法不以获得精确半数致死量(LD50)为研究目标,即不以动物死亡作为最终结果判定标准,降低了实验动物的死亡率,提高了动物福利。UDP法与Horn’s法很相似,系列剂量都有相对固定的剂量级数因子,都以动物死亡为重要的结果判断指标,都能获得确切的LD50值及其95%CI;但UDP更适合染毒后短期(48 h内)死亡的急性毒性评价。[结论]可根据受试物的性质和已知资料,选择合适的急性经口毒性替代方法代替传统Horn’s法。
[Abstract]:[objective] to compare the operability and consistency of four acute oral toxicity test methods, and analyze their application value and significance in acute toxicity evaluation of chemicals. [methods] three known chemicals (p-phenylenediamine, hydroquinone, p-phenylenediamine, hydroquinone) Boric acid was used to evaluate the acute oral toxicity of rats by fixed dose method (FDP), up and down increase / decrease dose method (UDP), acute toxicity classification method (ATC) and traditional Hornsberg method. The consistency of the classification of chemical toxicity was compared, and the animal use, dose selection and observation index were analyzed synthetically. [results] the three chemicals were determined by four methods respectively. The results of the three chemical classification methods were consistent with those of the GHSs. 3 alternative methods were all based on the sequential principle, and the number of experimental animals was less. But the experiment cycle is longer. FDP method and ATC method do not aim at obtaining accurate 50% lethal dose (LD50), that is, do not regard animal death as the final result criterion, and reduce the mortality rate of experimental animals. The animal welfare. UDP method is very similar to the Horn's method. The series of doses have relatively fixed dose progression factors, and all of them take animal death as the important result judgment index. Both of them could obtain the exact LD50 value and 95 CI, but UDP was more suitable for acute toxicity evaluation of death within 48 hours after exposure. [conclusion] according to the properties and known data of the samples, a suitable alternative method of acute oral toxicity can be selected instead of the traditional Horn's method.
【作者单位】：上海市疾病预防控制中心毒性评价科;
【分类号】：R114

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