Abstract Traditional in vivo inhalation studies to inform hazard identification and risk assessment are time-intensive and financially expensive. Cell culture models combined with aerosol exposure systems have shown promise as surrogates in screening assays when multiple substances require preliminary information on hazard potential associated with aerosolized materials. This paper presents two different aerosol exposure apparatuses: a settling chamber and a gentle impactor. Both apparatuses have been demonstrated for aerosol delivery capable of exposing cells in culture at the air-liquid interface. The settling chamber was constructed with simple design specifications, but exhibited a low deposition efficiency. The gentle impactor required a more sophisticated design based on aerosol dynamics of target size for the droplet delivery, but ultimately produced 64.25-fold greater deposition efficiency than the settling chamber. This led to a shorter exposure duration for the same dosage. It also enabled consistent exposure to the same sized aerosols. From these results, the gentle impactor shows promise as a high-throughput exposure tool that could be used in conjunction with cell-based co-culture models. Using a triple cell co-culture model of epithelial, dendritic, and macrophage cell-types, the induced inflammatory markers produced a more definitive dose-response for known irritants and positive indication for sensitizers. The materials tested include toluene-2,4-diisocyanate and trimellitic anhydride as known respiratory sensitizers; silica as a known respiratory irritant; and d -limonene as a known dermal sensitizer. Conversely, when using single cell monolayers, no significant different responses in inflammatory biomarkers was observed, suggesting cellular cross-talk is important. Evaluation of the ability to deliver aerosolized substances consistently and measure cytotoxicity and inflammatory endpoints is possible and demonstrates a potential high throughput screening tool.

中文翻译：

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气溶胶科学杂志传递的气溶胶剂量与炎症反应之间的联系：将肺细胞共培养系统暴露于选定的过敏原和刺激物

摘要 传统的体内吸入研究为危害识别和风险评估提供信息，既费时又费钱。当多种物质需要有关与气雾化材料相关的潜在危害的初步信息时，细胞培养模型与气溶胶暴露系统相结合已显示出作为筛选试验的替代品的前景。本文介绍了两种不同的气溶胶暴露装置：沉降室和温和的撞击器。两种装置都已被证明用于气溶胶递送，能够在气液界面处暴露培养细胞。沉降室的设计规格简单，但沉积效率低。温和的撞击器需要基于液滴输送目标尺寸的气溶胶动力学进行更复杂的设计，但最终产生的沉积效率比沉降室高 64.25 倍。这导致相同剂量的暴露时间更短。它还能够持续暴露于相同大小的气溶胶。从这些结果来看，温和的撞击器显示出作为一种高通量暴露工具的前景，可以与基于细胞的共培养模型结合使用。使用上皮细胞、树突细胞和巨噬细胞类型的三细胞共培养模型，诱导炎症标志物对已知刺激物产生更明确的剂量反应，并对致敏物产生阳性指示。测试的材料包括甲苯-2,4-二异氰酸酯和偏苯三酸酐作为已知的呼吸致敏剂；二氧化硅作为已知的呼吸道刺激物；d-柠檬烯作为已知的皮肤致敏剂。相反，当使用单细胞单层时，没有观察到炎症生物标志物的显着不同反应，表明细胞串扰很重要。评估持续输送雾化物质和测量细胞毒性和炎症终点的能力是可能的，并证明了一种潜在的高通量筛选工具。