Abstract

There are multiple in vitro and ex vivo eye irritation and corrosion test methods that are available as internationally harmonized test guidelines for regulatory use. Despite their demonstrated usefulness to a broad range of substances through inter-laboratory validation studies, they have not been widely adopted for testing agrochemical formulations due to a lack of concordance with parallel results from the traditional regulatory test method for this endpoint, the rabbit eye test. The inherent variability of the rabbit test, differences in the anatomy of the rabbit and human eyes, and differences in modelling exposures in rabbit eyes relative to human eyes contribute to this lack of concordance. Ultimately, the regulatory purpose for these tests is protection of human health, and, thus, there is a need for a testing approach based on human biology. This paper reviews the available in vivo, in vitro and ex vivo test methods with respect to their relevance to human ocular anatomy, anticipated exposure scenarios, and the mechanisms of eye irritation/corrosion in humans. Each of the in vitro and ex vivo methods described is generally appropriate for identifying non-irritants. To discriminate among eye irritants, the human three-dimensional epithelial and full thickness corneal models provide the most detailed information about the severity of irritation. Consideration of the mechanisms of eye irritation, and the strengths and limitations of the in vivo, in vitro and ex vivo test methods, show that the in vitro/ex vivo methods are as or more reflective of human biology and less variable than the currently used rabbit approach. Suggestions are made for further optimizing the most promising methods to distinguish between severe (corrosive), moderate, mild and non-irritants and provide information about the reversibility of effects. Also considered is the utility of including additional information (e.g. physical chemical properties), consistent with the Organization for Economic Cooperation and Development’s guidance document on an integrated approach to testing and assessment of potential eye irritation. Combining structural and functional information about a test substance with test results from human-relevant methods will ensure the best protection of humans following accidental eye exposure to agrochemicals.

摘要

有多种体外和离体眼睛刺激和腐蚀测试方法，可作为监管使用的国际统一测试指南。尽管通过实验室间验证研究证明它们对广泛的物质有用，但由于与该终点的传统监管测试方法的平行结果缺乏一致性，它们尚未被广泛用于测试农用化学品配方，兔眼测试. 兔子测试的固有可变性、兔子和人眼解剖结构的差异以及兔子眼睛相对于人眼的建模暴露的差异导致了这种一致性的缺乏。最终，这些测试的监管目的是保护人类健康，因此需要一种基于人类生物学的测试方法。本文回顾了可用的体内、体外和离体测试方法与人体眼部解剖结构的相关性、预期的暴露场景以及人类眼睛刺激/腐蚀的机制。所描述的每种体外和离体方法通常适用于识别非刺激性物质。为了区分眼睛刺激物，人体三维上皮和全厚度角膜模型提供了有关刺激严重程度的最详细信息。考虑眼睛刺激的机制，以及体内、体外和离体测试方法的优势和局限性，表明体外/离体方法与目前使用的兔方法一样或更多地反映了人类生物学，并且变化较小。建议进一步优化最有前途的方法，以区分严重（腐蚀性）、中度、轻度和无刺激性，并提供有关影响可逆性的信息。还考虑了包括附加信息（例如物理化学特性）的效用，这与经济合作与发展组织关于测试和评估潜在眼睛刺激的综合方法的指导文件一致。将测试物质的结构和功能信息与人类相关方法的测试结果相结合，将确保在眼睛意外接触农用化学品后为人类提供最佳保护。