The Procter & Gamble Company, Brussels, Belgium.
Toxicol In Vitro. 2010 Feb;24(1):1-9. doi: 10.1016/j.tiv.2009.05.019. Epub 2009 May 31.
In spite of over 20 years of effort, no single in vitro assay has been developed and validated as a full regulatory replacement for the Draize Eye Irritation test. However, companies have been using in vitro methods to screen new formulations and in some cases as their primary assessment of eye irritation potential for many years. The present report shows the outcome of an Expert Meeting convened by the European Centre for the Validation of Alternative Methods in February 2005 to identify test strategies for eye irritation. In this workshop test developers/users were requested to nominate methods to be considered as a basis for the identification of such testing strategies. Assays were evaluated and categorized based on their proposed applicability domains (e.g., categories of irritation severity, modes of action, chemical class, physicochemical compatibility). The analyses were based on the data developed from current practice and published studies, the ability to predict depth of injury (within the applicable range of severity), modes of action that could be addressed and compatibility with different physiochemical forms. The difficulty in predicting the middle category of irritancy (e.g. R36, GHS Categories 2A and 2B) was recognized. The testing scheme proposes using a Bottom-Up (begin with using test methods that can accurately identify non-irritants) or Top-Down (begin with using test methods that can accurately identify severe irritants) progression of in vitro tests (based on expected irritancy). Irrespective of the starting point, the approach would identify non-irritants and severe irritants, leaving all others to the (mild/moderate) irritant GHS 2/R36 categories.
尽管已经努力了 20 多年,但仍然没有开发出一种完全可以替代 Draize 眼刺激试验的体外检测方法。然而,多年来,许多公司一直在使用体外方法来筛选新的配方,在某些情况下,还将其作为评估眼部刺激性的主要方法。本报告展示了欧洲替代方法验证中心于 2005 年 2 月召开的一次专家会议的结果,该会议旨在确定眼部刺激的测试策略。在这个研讨会上,测试开发者/用户被要求提名可被视为确定这种测试策略的基础的方法。根据其提议的适用性领域(例如,刺激严重程度类别、作用模式、化学类别、物理化学相容性)对试验进行评估和分类。分析基于当前实践和已发表研究的数据,预测损伤深度(在适用的严重程度范围内)的能力、可以解决的作用模式以及与不同物理化学形式的兼容性。识别中度刺激性(例如 R36、GHS 类别 2A 和 2B)的困难得到了认可。该测试方案提出使用自下而上(从能够准确识别非刺激性的测试方法开始)或自上而下(从能够准确识别刺激性的测试方法开始)的体外测试方案(基于预期的刺激性)。无论从哪个起点开始,这种方法都将识别非刺激性和刺激性很强的物质,而将所有其他物质(轻度/中度)刺激性的 GHS 2/R36 类别留给其他方法。