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发育毒理学中的替代模型。

Alternative models in developmental toxicology.

机构信息

Division of Personalized Nutrition and Medicine, FDA/National Center for Toxicological Research, Jefferson, AR 72079, USA.

出版信息

Syst Biol Reprod Med. 2012 Feb;58(1):10-22. doi: 10.3109/19396368.2011.648302.

Abstract

In light of various pressures, toxicologists have been searching for alternative methods for safety testing of chemicals. According to a recent policy in the European Union (Regulation, Evaluation Authorisation and Restriction of Chemicals, REACH), it has been estimated that over the next twelve to fifteen years, approximately 30,000 chemicals may need to be tested for safety, and under current guidelines such testing would require the use of approximately 7.2 million laboratory animals [ Hofer et al. 2004 ]. It has also been estimated that over 80% of all animals used for safety testing under REACH legislation would be used for examining reproductive and developmental toxicity [Hofer et al., 2004]. In addition to REACH initiatives, it has been estimated that out of 5,000 to 10,000 new drug entities that a pharmaceutical company may start with, only one is finally approved by the Food and Drug Administration at a cost of over one billion dollars [ Garg et al. 2011 ]. A large portion of this cost is due to animal testing. Therefore, both the pharmaceutical and chemical industries are interested in using alternative models and in vitro tests for safety testing. This review will examine the current state of three alternative models - whole embryo culture (WEC), the mouse embryonic stem cell test (mEST), and zebrafish. Each of these alternatives will be reviewed, and advantages and disadvantages of each model will be discussed. These models were chosen because they are the models most commonly used and would appear to have the greatest potential for future applications in developmental toxicity screening and testing.

摘要

鉴于各种压力,毒理学家一直在寻找替代方法来测试化学品的安全性。根据欧盟最近的一项政策(化学品的注册、评估、授权和限制法规,REACH),据估计,在未来十二到十五年内,大约有 30000 种化学品需要进行安全性测试,根据现行指南,这种测试需要使用大约 720 万只实验动物[Hofer 等人,2004]。据估计,在 REACH 法规下用于安全性测试的所有动物中,超过 80%将用于检查生殖和发育毒性[Hofer 等人,2004]。除了 REACH 倡议,据估计,一家制药公司可能从 5000 到 10000 种新的药物实体开始,最终只有一种能得到美国食品和药物管理局的批准,成本超过 10 亿美元[Garg 等人,2011]。这部分成本的很大一部分是由于动物测试。因此,制药和化工行业都有兴趣使用替代模型和体外测试来进行安全性测试。本综述将检查三种替代模型的现状——全胚胎培养(WEC)、小鼠胚胎干细胞测试(mEST)和斑马鱼。将对这些替代方法逐一进行审查,并讨论每种模型的优缺点。选择这些模型是因为它们是最常用的模型,并且似乎在未来的发育毒性筛选和测试中具有最大的应用潜力。

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