Akita Masaharu
Department of Nutrition and Dietetics, Faculty of Family and Consumer Sciences, Kamakura Women's University, Kamakura City, Japan.
Yakugaku Zasshi. 2008 May;128(5):765-72. doi: 10.1248/yakushi.128.765.
Currently, the European Centre for the Validation of Alternative Methods in the EU appears to be at the forefront of the development of alternative methods for developmental toxicity test (reproductive/developmental toxicity test). Why is it difficult to develop alternative methods for developmental toxicity test in comparison with other toxicity tests? In developmental toxicity test, chemical substances first enter the bloodstream and then reach the placenta via metabolism in the liver and other organs. After further metabolism in the placenta, chemical substances finally reach the fetus, where they affect fetal development. The difference in the in vivo route of chemical substances is an important reason for the difficulty in the establishment of new methods for developmental toxicologic test in comparison with general toxicity tests. According to the EU, the use of "in silico" techniques for developmental toxicity test may be difficult, and I agree with this. The in silico technique is basically a method for prediction of toxicologic effects from existing data, and cannot predict new effects, because data obtained by developmental toxicologic test are too complex. Three techniques are now being examined to overcome the difficulty in changing the method of developmental toxicologic test: the technique utilizing embryonic stem cells; micromass culture technique; and the whole embryonic culture technique. In this symposium, the current status of developmental toxicity tests and the three techniques being examined in the EU are introduced, and opinions on future progress are presented.
目前，欧盟的欧洲替代方法验证中心似乎在发育毒性试验（生殖/发育毒性试验）替代方法的开发方面处于领先地位。与其他毒性试验相比，为什么开发发育毒性试验的替代方法会如此困难呢？在发育毒性试验中，化学物质首先进入血液，然后通过肝脏和其他器官的代谢到达胎盘。在胎盘中进一步代谢后，化学物质最终到达胎儿体内，在那里它们会影响胎儿发育。与一般毒性试验相比，化学物质在体内的途径差异是难以建立发育毒理学试验新方法的一个重要原因。据欧盟称，将“计算机模拟”技术用于发育毒性试验可能存在困难，对此我表示认同。计算机模拟技术基本上是一种根据现有数据预测毒理学效应的方法，由于发育毒理学试验获得的数据过于复杂，所以无法预测新的效应。目前正在研究三种技术以克服改变发育毒理学试验方法的困难：利用胚胎干细胞的技术；微团培养技术；以及全胚胎培养技术。在本次研讨会上，介绍了欧盟发育毒性试验的现状以及正在研究的这三种技术，并就未来的进展发表了意见。
