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首页> 外文期刊>Journal of applied toxicology >Development of a multiparametric in vitro model of skin sensitization
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Development of a multiparametric in vitro model of skin sensitization

机译：一种多前述皮肤敏化体外模型的发展

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Most animal experiments on cosmetics safety are prohibited and since March 2013, this obligation includes sensitization tests. However, until now there has been no validated alternative in vitro method. In this work, 400 compounds used in the cosmetic industry were selected to cover the greatest diversity of structures, biological activities and sensitizing potential. These molecules were submitted to a series of tests aimed at reproducing essential steps in sensitization and to distinguish between sensitization and irritations, i.e., transcutaneous permeation (factor A), haptenation (factor B), sensitization cytokines production (factor C) and acute toxicity (factor D). The transcutaneous diffusion was measured on human skin explants using Franz cells. Haptenation was tested in solution on human serum albumin. Sensitization cytokine production was investigated by measurement of interleukin-18 release by keratinocytes. Acute toxicity was determined using an 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(75) cell viability test. As only sufficiently stable, soluble and detectable compounds are usable, 33, 72, 68 and 68 molecules were finally tested on factors A, B, C and D, respectively, and 32 were completely screened by the four factors. The individual correlation of the four factors with the reference in vivo tests was limited but the combination of these factors led to a correlation between in vivo and in vitro assays of 81.2% and the safety of the test (risk of false negative) reached 96.8%. The techniques employed are simple and inexpensive and this model of four tests appears as a promising technique to evaluate in vitro the skin sensitization potential of unknown molecules. Copyright (c) 2014 John Wiley & Sons, Ltd.
机译：大多数关于化妆品安全的动物实验是禁止的，自2013年3月以来，这项义务包括致敏试验。但是，直到现在，没有经过验证的替代方法。在这项工作中，选择了化妆品工业中使用的400种化合物，以涵盖最大的结构，生物活性和敏感潜力。将这些分子提交至一系列测试，该试验旨在再现敏感性的基本步骤，并区分敏化和刺激性，即经皮渗透（因子A），海囊化（因子B），敏化细胞因子产生（因子C）和急性毒性（因子d）。在使用Franz细胞的人体皮肤外植物上测量经皮扩散。在人血清白蛋白溶液中测试了海藻化。通过通过角质形成细胞测量白细胞介素-18释放来研究敏化细胞因子的产生。使用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴铵（75）细胞活力试验测定急性毒性。仅仅是足够稳定的，可溶性和可检测的化合物是可用的，最终测试33,72,68和68分子，分别对因子A，B，C和D分别进行了测试，并通过四个因素完全筛选32个。在体内试验中具有参考的四种因素的个体相关性受到限制，但这些因素的组合导致体内和体外测定的相关性81.2％，试验的安全性（假阴性的风险）达到96.8％ 。所采用的技术简单且便宜，这种四种测试模型表现为评估未知分子的皮肤敏感潜力的有希望的技术。版权所有（c）2014 John Wiley＆Sons，Ltd。

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