Abstract：
As part of the development of new approach methodologies (NAMs), numerous in vitro methods are being developed to characterize the potential toxicity of inhalable xenobiotics (gases, volatile organic compounds, polycyclic aromatic hydrocarbons, particulate matter, nanoparticles). However, the materials and methods employed are extremely diverse, and no single method is currently in use. Method standardization and validation would raise trust in the results and enable them to be compared. This four-part review lists and compares biological models and exposure methodologies before describing measurable biomarkers of exposure or effect. The first section emphasizes the importance of developing alternative methods to reduce, if not replace, animal testing (3R principle). The biological models presented are mostly to cultures of epithelial cells from the respiratory system, as the lungs are the first organ to come into contact with air pollutants. Monocultures or cocultures of primary cells or cell lines, as well as 3D organotypic cultures such as organoids, spheroids and reconstituted tissues, but also the organ(s) model on a chip are examples. The exposure methods for these biological models applicable to airborne compounds are submerged, intermittent, continuous either static or dynamic. Finally, within the restrictions of these models (i.e. relative tiny quantities, adhering cells), the mechanisms of toxicity and the phenotypic markers most commonly examined in models exposed at the air-liquid interface (ALI) are outlined.
摘要：
作为开发新方法方法(NAM)的一部分，正在开发许多体外方法来表征可吸入外源性物质的潜在毒性(气体，挥发性有机化合物，多环芳烃，颗粒物,纳米粒子)。然而,所用的材料和方法极其多样，并且目前没有使用单一方法。方法标准化和验证将提高对结果的信任，并使它们能够进行比较。在描述可测量的暴露或影响的生物标志物之前，这四个部分的综述列出并比较了生物模型和暴露方法。第一部分强调了开发替代方法的重要性，如果不更换，动物试验（3R原理）。提出的生物模型主要是针对呼吸系统上皮细胞的培养物，因为肺是第一个与空气污染物接触的器官。原代细胞或细胞系的单一培养或共培养，以及3D器官型培养，如类器官，球体和重组组织，而且芯片上的器官模型也是例子。这些适用于空气传播化合物的生物模型的暴露方法被淹没，间歇性,连续的静态或动态。最后,在这些模型的限制内(即相对微小的数量，粘附细胞)，概述了在暴露于空气-液体界面（ALI）的模型中最常见的毒性机制和表型标志物。
