Courtellemont P, Pannetier M, Biesse J P, Larnicol M, Baret J P, Breda B
Lead Laboratory, Parfums Christian Dior SA, Saint Jean de Braye, France.
Toxicol In Vitro. 1999 Apr;13(2):295-304. doi: 10.1016/s0887-2333(98)00081-2.
In the context of the 6th Amendment of the European Directive on Cosmetics, several cosmetic companies concentrate their basic research on the development of the best adapted battery of in vitro tests able to be incorporated in the ocular risk assessment process. Consequently, the European Cosmetic Toiletry and Perfumery Association (COLIPA) has initiated an international multicentric study with the main purpose to validate available alternatives in vitro methods for assessing the eye irritation potential of cosmetic raw materials and formulations. The alternative methods assessed in this validation study were chosen since all of these tests had already been used and continue to be conducted in the risk assessment process. The different endpoints of these assays are mainly biological parameters except for the biochemical assay named EYTEX(TM). In this article, the defined prediction models and the different protocols used in the COLIPA study are described. Then, the EYTEX assay results are presented and discussed in details in order to understand the failure of this assay during this validation study. The relevance and the reliability of the EYTEX assay were particularly low in two laboratories, whereas one laboratory presented acceptable data with a low compatibility with tested samples. These results underline the problem of the complex qualification process of this assay, since sometimes the same sample has been qualified with different protocols in the three laboratories. This validation study also demonstrates that, in the case of EYTEX assay, the criteria used to establish a prediction model have not been rigorous enough. For instance, the mixture of all the EYTEX protocols is not suitable for the establishment of a well-adapted prediction model. Furthermore, a clearer definition of limitations of the EYTEX assay seems to be necessary to better harmonize the qualification procedure in the three laboratories. The COLIPA validation process clearly demonstrated that the EYTEX assay was first, not suitable for the assessment of the eye irritation potential of surfactants and formulations based on surfactants, and secondly not ready for a validation study requiring the establishment of adequate and well defined mathematical prediction models. However, internal comparative studies with specific benchmarks on emulsions containing a low percentage of surfactants may be more adaptable to this type of assay.
在欧洲化妆品指令第六次修订的背景下，几家化妆品公司将其基础研究集中于开发最适用的体外测试组合，以便纳入眼部风险评估流程。因此，欧洲化妆品、盥洗用品和香料协会（COLIPA）发起了一项国际多中心研究，其主要目的是验证用于评估化妆品原料和配方眼部刺激潜力的现有体外替代方法。之所以选择在此验证研究中评估的替代方法，是因为所有这些测试已在风险评估过程中使用并仍在进行。除名为EYTEX™的生化测定外，这些测定的不同终点主要是生物学参数。在本文中，描述了COLIPA研究中定义的预测模型和使用的不同方案。然后，详细介绍并讨论了EYTEX测定结果，以便了解该测定在此次验证研究中的失败情况。在两个实验室中，EYTEX测定的相关性和可靠性特别低，而一个实验室提供了可接受的数据，但与测试样品的兼容性较低。这些结果凸显了该测定复杂的鉴定过程问题，因为有时在三个实验室中，相同的样品采用了不同的方案进行鉴定。该验证研究还表明，就EYTEX测定而言，用于建立预测模型的标准不够严格。例如，所有EYTEX方案的混合不适合建立一个合适的预测模型。此外，似乎有必要更明确地界定EYTEX测定的局限性，以便更好地协调三个实验室的鉴定程序。COLIPA的验证过程清楚地表明：首先，EYTEX测定不适用于评估表面活性剂以及基于表面活性剂的配方的眼部刺激潜力；其次，它还未准备好进行一项需要建立充分且定义明确的数学预测模型的验证研究。然而，针对含低百分比表面活性剂的乳液进行的内部特定基准比较研究可能更适合这类测定。
