化学物(药物)毒性测试替代体系的建立及应用  

Establishment and application of toxicity testing alternative system for chemicals (new drugs)

作　　者：施畅[1] 马华智[1] 王全军[1] 吴纯启[1] 原野[1] 石富江[1] 荆淑芳[1] 王建京[1] 廖明阳[1] 

机构地区：[1]军事医学科学院毒物药物研究所,抗毒药物与毒理学国家重点实验室,北京100850

出　　处：《中国比较医学杂志》2017年第5期6-8,共3页Chinese Journal of Comparative Medicine

基　　金：北京市科委科技计划项目(H030230150130);国家科技重大专项课题(2008ZX09305-003,2012ZX09301-003-008,2013ZX09301303)

摘　　要：当前对化学物进行毒性评价的整体动物试验由于试验周期长、成本高,存在种属差异和剂量差异,导致其实验结果在预测人体毒性风险时受到一定的限制。本研究针对化学物安全性评价及风险评估所依赖的毒作用终点(遗传毒性、致癌性、生殖毒性、急性毒性、一般毒性),按照动物试验替代、减少、优化的"3R"原则,建立相应的毒性测试替代筛选体系。该体系涵盖毒性评价的绝大多数终点,并结合分子生物学技术对毒性试验进行整合,优化了多种动物试验操作方法,以期缩短实验周期、降低实验成本、提高动物福利。同时该体系是基于毒作用机制进行的毒性评价,因此试验结果具有较高的人体相关性。There are some shortcomings of animal experiments applied in chemical toxicity testing, such as long period, large cost, species differences and dose differences, which limit the use of animal experiments＇ results in predicting human toxicity.Accordingly, we established a toxicity testing alternative screening system in line with the toxicity endpoints which required in chemical safety evaluation and risk assessment （genotoxicity, carcinogenicity, reproductive toxicity, acute toxicity and general toxicity） based on ＂3R＂ principles （replacement, reduction, refinement） for animal experiments.This system covers most of the endpoints of toxicity assessment, and molecular biology technology was also applied to integrate the toxicity test, as well as some operation was optimized in order to shorten the experimental period, reduce experimental costs, improve animal welfare.Furthermore, the results from the screening system have higher clinical relevance because it is based on the toxicity mechanisms.

关 键 词：毒性测试 替代策略 减少性替代 替代性研究 优化性替代 

分 类 号：R-33[医药卫生]