Recent research on in vitro systems has focused on mimicking the in vivo situation of cells within the respiratory system. However, few studies have predicted inhalation toxicity using conventional and simple submerged two-dimensional (2D) cell culture models. We investigated the conventional submerged 2-D cell culture model as a method for the prediction of acute inhalation toxicity. Median lethal concentration (LC₅₀) (rat, inhalation, 4 h) and half maximal inhibitory concentration (IC₅₀) (lung or bronchial cell, 24 h) data for 59 substances were obtained from the literature and by experiments. Cytotoxicity assays were performed on 44 substances with reported LC₅₀, but without IC₅₀, data to obtain the IC₅₀ values. A weak correlation was observed between the IC₅₀ and LC₅₀ of all substances. Semi-volatile organic compounds (SVOCs) and non-VOCs (NVOCs) (16 substances) with a water solubility of ≥1 g/L were strongly correlated between 24-h IC₅₀ and 4-h LC₅₀, and this had an excellent predictive ability to distinguish between Categories 1–3 and 4 (Globally Harmonized System classification for acute inhalation toxicity). Our results suggest that the submerged 2-D cell culture model may be used to predict in vivo acute inhalation toxicity for substances with a water solubility of ≥1 g/L in SVOCs and NVOCs.

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使用人肺上皮细胞系的细胞毒性数据预测急性吸入毒性

最近对体外系统的研究集中在模拟呼吸系统内细胞的体内情况。然而，很少有研究使用传统和简单的浸没式二维 (2D) 细胞培养模型预测吸入毒性。我们研究了传统的浸没式 2-D 细胞培养模型作为预测急性吸入毒性的方法。59 种物质的半数致死浓度（LC ₅₀）（大鼠，吸入，4 小时）和半数最大抑制浓度（IC ₅₀）（肺或支气管细胞，24 小时）数据来自文献和实验。对 44 种物质进行了细胞毒性试验，报告了 LC ₅₀，但没有 IC ₅₀，获得 IC 的数据_{50 个}值。在所有物质的 IC ₅₀和 LC ₅₀之间观察到弱相关性。水溶性≥1 g/L 的半挥发性有机化合物 (SVOCs) 和非挥发性有机化合物 (NVOCs)（16 种物质）在 24-h IC ₅₀和 4-h LC ₅₀之间具有很强的相关性，这具有极好的区分第 1-3 类和第 4 类（急性吸入毒性全球协调系统分类）的预测能力。我们的结果表明，浸没式二维细胞培养模型可用于预测在 SVOC 和 NVOC 中水溶性≥1 g/L 的物质的体内急性吸入毒性。