Abstract

Respiratory sensitization has been considered an important toxicological endpoint, because of the severe risk to human health. A great part of sensitization events were caused by low molecular weight (< 1000) respiratory sensitizers in the past decades. However, there is currently no widely accepted test method that can identify prospective low molecular weight respiratory sensitisers. Herein, we performed the study of modeling and insights into molecular basis of low molecular weight respiratory sensitizers with a high-quality data set containing 136 respiratory sensitizers and 518 nonsensitizers. We built a number of classification models by using OCHEM tools, and a consensus model was developed based on the ten best individual models. The consensus model showed good predictive ability with a balanced accuracy of 0.78 and 0.85 on fivefold cross-validation and external validation, respectively. The readers can predict the respiratory sensitization of organic compounds via https://ochem.eu/article/114857. The effect of several molecular properties on respiratory sensitization was also evaluated. The results indicated that these properties differ significantly between respiratory sensitizers and nonsensitizers. Furthermore, 14 privileged substructures responsible for respiratory sensitization were identified. We hope the models and the findings could provide useful help for environmental risk assessment.

Graphic abstract

摘要

由于对人类健康的严重风险，呼吸致敏被认为是一个重要的毒理学终点。在过去的几十年中，很大一部分致敏事件是由低分子量 (< 1000) 呼吸道致敏剂引起的。然而，目前还没有被广泛接受的测试方法可以识别潜在的低分子量呼吸致敏物。在此，我们使用包含 136 种呼吸致敏剂和 518 种非致敏剂的高质量数据集对低分子量呼吸致敏剂的分子基础进行建模和洞察。我们使用 OCHEM 工具构建了多个分类模型，并基于 10 个最佳个体模型开发了一个共识模型。共识模型显示出良好的预测能力，平衡精度为 0.78 和 0。五重交叉验证和外部验证分别为 85。读者可以通过 https://ochem.eu/article/114857 预测有机化合物的呼吸致敏性。还评估了几种分子特性对呼吸致敏的影响。结果表明，这些特性在呼吸致敏剂和非致敏剂之间存在显着差异。此外，还确定了 14 个负责呼吸致敏的特权子结构。我们希望这些模型和研究结果能为环境风险评估提供有用的帮助。结果表明，这些特性在呼吸致敏剂和非致敏剂之间存在显着差异。此外，还确定了 14 个负责呼吸致敏的特权子结构。我们希望这些模型和研究结果能为环境风险评估提供有用的帮助。结果表明，这些特性在呼吸致敏剂和非致敏剂之间存在显着差异。此外，还确定了 14 个负责呼吸致敏的特权子结构。我们希望这些模型和研究结果能为环境风险评估提供有用的帮助。

图形摘要