Kao Corporation, Safety Science Research Laboratories.
Faculty of Engineering, Department of Materials Science and Engineering, Yokohama National University.
J Toxicol Sci. 2018;43(7):407-422. doi: 10.2131/jts.43.407.
The Short Time Exposure (STE) test method is an in vitro method for assessing the eye irritation potential of chemicals and is used to classify the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Category 1 and No Category (NC). The method has been adopted by the Organisation for Economic Co-operation and Development (OECD) as test guideline (TG) 491 since 2015. While this method can be used to classify GHS NC, it is not suitable for testing highly volatile substances and solids other than surfactants. Here we evaluated highly volatile substances to expand the applicability domain. According to TG 491, acetone, ethanol, iso-propanol, and methyl acetate as highly volatile substances resulted in false negatives. Saline was selected as a solvent of these false negatives. In this study, mineral oil was used as the solvent, because these false negatives were amphiphilic. Based on this change, four highly volatile substances were correctly evaluated. The predictive performance for classifying GHS NC was then verified using a substance dataset constructed in reference to the Draize eye test Reference Database and STE Summary Review Document. The accuracy and false-negative rate were 86.6% (194/224) and 3.8% (3/80), respectively. Collectively, the applicability domain was expanded by changing the solvent to mineral oil for highly volatile substances, and the predictive performance for the new applicability domain including highly volatile substances was excellent. The STE test method is suitable to classify GHS NC, indicating its applicability as a test method in a bottom-up approach.
短时间暴露（STE）测试方法是一种用于评估化学品眼部刺激性的体外方法，用于对全球化学品统一分类和标签制度（GHS）第 1 类和无类别（NC）进行分类。该方法自 2015 年以来被经济合作与发展组织（OECD）采用为测试指南（TG）491。虽然该方法可用于对 GHS NC 进行分类，但它不适用于测试高度挥发性物质和除表面活性剂以外的固体。在这里，我们评估了高度挥发性物质以扩展适用性领域。根据 TG 491，作为高度挥发性物质的丙酮、乙醇、异丙醇和乙酸甲酯导致假阴性。选择生理盐水作为这些假阴性的溶剂。在本研究中，矿物油被用作溶剂，因为这些假阴性是两亲性的。基于这一变化，正确评估了四种高度挥发性物质。然后使用参照 Draize 眼试验参考数据库和 STE 总结审查文件构建的物质数据集来验证对 GHS NC 分类的预测性能。准确性和假阴性率分别为 86.6%（194/224）和 3.8%（3/80）。总之，通过将溶剂更改为高度挥发性物质的矿物油，扩展了适用性领域，包括高度挥发性物质在内的新适用性领域的预测性能非常出色。STE 测试方法适用于对 GHS NC 进行分类，表明其作为自下而上方法中的测试方法具有适用性。
