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Pre-validation study of alternative developmental toxicity test using mouse embryonic stem cell-derived embryoid bodies
Food and Chemical Toxicology ( IF 4.3 ) Pub Date : 2018-10-16 , DOI: 10.1016/j.fct.2018.10.044
Jae-Hwan Lee , Seon Young Park , Changhwan Ahn , Cho-Won Kim , Ji-eun Kim , Na Rae Jo , Hee Young Kang , Yeong-Min Yoo , Eui-Man Jung , Eun Mi Kim , Ki-Suk Kim , Kyung-Chul Choi , Sung Duck Lee , Eui-Bae Jeung

The embryoid body test (EBT) is a developmental toxicity test method that assesses the half inhibitory concentrations of substances in the area of embryoid bodies (EBs), and in the viability of mouse embryonic stem cells (ESCs) and fibroblasts (3T3 cells) following chemical exposure for three and four days, respectively. In the previous study, the EBT showed more advanced than the embryonic stem cell test (EST) from the European Centre for the Validation of Alternative Methods (ECVAM) applying cardiac differentiation of mouse ESCs, because the EBT greatly reduced the exposure time, labor, and amount of materials required, and misclassification of embryotoxic potential. This pre-validation study evaluated the predictive accuracy of the EBT using 26 coded test substances by two steps: intra-laboratory and inter-laboratory reproducibility tests. Since some substances have different embryotoxic potentials at different pregnancy periods, in this study, a new prediction model consisting of non-toxic and toxic classes was used, instead of the existing prediction model assessing embryotoxicants in four classes. The results of the intra- and inter-laboratory tests were highly accurate (above 80%) when substances were classified using the predictive model. In conclusion, EBT can accurately classify various embryotoxicants in a short time with less effort and greater validation.



中文翻译:

小鼠胚胎干细胞来源的类胚体替代发育毒性试验的预验证研究

胚状体测试(EBT)是一种发育毒性测试方法,用于评估以下物质在胚状体(EBs)区域以及小鼠胚胎干细胞(ESCs)和成纤维细胞(3T3细胞)生存力中的一半抑制浓度。化学暴露分别为三天和四天。在先前的研究中,EBT显示比欧洲应用小鼠ESCs心脏替代方法验证中心(ECVAM)的胚胎干细胞测试(EST)更先进,因为EBT大大减少了暴露时间,人工,所需材料的数量,以及对胚胎毒性潜能的错误分类。这项验证前研究通过以下两个步骤对使用26种编码测试物质的EBT的预测准确性进行了评估:实验室内部和实验室之间的可重复性测试。由于某些物质在不同妊娠期具有不同的胚胎毒性潜能,因此在本研究中,使用了一个由无毒和有毒类别组成的新预测模型,而不是现有的评估四类胚胎毒性的预测模型。当使用预测模型对物质进行分类时,实验室内和实验室间测试的结果非常准确(超过80%)。总之,EBT可以在短时间内以更少的努力和更大的准确性对各种胚胎毒物进行准确分类。当使用预测模型对物质进行分类时,实验室内和实验室间测试的结果非常准确(超过80%)。总之,EBT可以在短时间内以更少的努力和更大的准确性对各种胚胎毒物进行准确分类。当使用预测模型对物质进行分类时,实验室内和实验室间测试的结果非常准确(超过80%)。总之,EBT可以在短时间内以更少的努力和更大的准确性对各种胚胎毒物进行准确分类。

更新日期:2018-10-16
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