Da Silva E, Hickey C, Ellis G, Hougaard K S, Sørli J B
Technical University of Denmark, Kgs. Lyngby, Denmark.
National Research Centre for the Working Environment, Copenhagen, Denmark.
Curr Res Toxicol. 2021 May 21;2:204-209. doi: 10.1016/j.crtox.2021.05.002. eCollection 2021.
To date there are no OECD validated alternative approaches to study toxicity following inhalation exposure to airborne chemicals. The available OECD test guidelines for acute inhalation toxicity aim to estimate a value of the lethal air concentration of the test chemical leading to the death of 50% of the exposed animals (LC), to satisfy hazard classification and labelling requirements. This paper explores the view that alternative approaches must compare to outcomes of existing guideline methods to become accepted and implemented in a regulatory context. This case study describes the initiatives taken to validate the lung surfactant bioassay, an cell-free method, and discusses the challenges faced. While the lung surfactant bioassay could not predict the GHS classification for acute inhalation toxicity of 26 chemicals, the assay successfully predicted the clinical signs of respiratory toxicity observed during or shortly after exposure as reported in registration dossiers. The lung surfactant bioassay is a promising alternative approach to assess the potential of chemicals to cause changes to respiration remaining after exposure (indicating decreased lung function), and can be combined with other test methods in an integrated approach to testing and assessment of inhaled substances.
迄今为止，经济合作与发展组织（OECD）尚未验证用于研究吸入空气中化学物质后的毒性的替代方法。现有的OECD急性吸入毒性测试指南旨在估算导致50%暴露动物死亡的受试化学物质的致死空气浓度值（LC），以满足危害分类和标签要求。本文探讨了一种观点，即替代方法必须与现有指南方法的结果进行比较，才能在监管环境中被接受和实施。本案例研究描述了为验证肺表面活性剂生物测定法（一种无细胞方法）所采取的举措，并讨论了所面临的挑战。虽然肺表面活性剂生物测定法无法预测26种化学物质的急性吸入毒性的全球化学品统一分类和标签制度（GHS）分类，但该测定法成功预测了注册卷宗中报告的暴露期间或暴露后不久观察到的呼吸毒性临床症状。肺表面活性剂生物测定法是一种很有前景的替代方法，可用于评估化学物质导致暴露后呼吸变化（表明肺功能下降）的可能性，并且可以与其他测试方法结合，以综合方式对吸入物质进行测试和评估。
