Workplace inhalation exposure to indium compounds has been reported to produce ‘indium lung disease’ characterized by pulmonary alveolar proteinosis (PAP), granulomas, and pulmonary fibrosis. However, there is little information about the pulmonary toxicity of nano-sized indium oxide (In₂O₃), which is widely used in various applications such as liquid crystal displays. In this study, we evaluated the time-course and dose-dependent lung injuries by In₂O₃ nanoparticles (NPs) after a single intratracheal instillation to rats. In₂O₃ NPs were instilled to female Wistar rats at 7.5, 30, and 90 cm²/rat and lung injuries were evaluated at day 1, 3, 7, 14, 30, 90, and 180 after a single intratracheal instillation. Treatment of In₂O₃ NPs induced worsening diverse pathological changes including PAP, persistent neutrophilic inflammation, type II cell hyperplasia, foamy macrophages, and granulomas in a time- and dose-dependent manner. PAP was induced from day 3 and worsened throughout the study. The concentrations of interleukin-1β, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in bronchoalveolar lavage fluid (BALF) showed dose- and time-dependent increases and the levels of these inflammatory mediators are consistent with the data of inflammatory cells in BALF and progressive lung damages by In₂O₃ NPs. This study suggests that a single inhalation exposure to In₂O₃ NPs can produce worsening lung damages such as PAP, chronic active inflammation, infiltration of foamy macrophages, and granulomas. The early onset and persistent PAP even at the very low dose (7.5 cm²/rat) implies that the re-evaluation of occupational recommended exposure limit for In₂O₃ NPs is urgently needed to protect workers.

据报道，工作场所吸入铟化合物会导致“肺铟疾病”，其特征是肺泡蛋白沉着症（PAP），肉芽肿和肺纤维化。然而，关于纳米级氧化铟（In ₂ O ₃）的肺毒性的信息很少，该纳米级氧化铟广泛用于诸如液晶显示器之类的各种应用中。在这项研究中，我们评估了在气管内滴注大鼠后In ₂ O ₃纳米颗粒（NPs）对肺的时程和剂量依赖性肺损伤。在_2个O _3中，分别以7.5、30和90 cm ^2将NPs注入雌性Wistar大鼠中在单次气管内滴注后第1、3、7、14、30、90和180天评估大鼠/大鼠和肺损伤。In ₂ O ₃ NP的治疗以时间和剂量依赖性方式诱导各种病理变化的恶化，包括PAP，持续性嗜中性粒细胞炎症，II型细胞增生，泡沫巨噬细胞和肉芽肿。从第3天开始诱导PAP，并在整个研究过程中恶化。支气管肺泡灌洗液（BALF）中白细胞介素1β，肿瘤坏死因子-α和单核细胞趋化蛋白1的浓度呈剂量和时间依赖性增长，这些炎性介质的水平与炎性细胞的数据一致。 In ₂ O _3对BALF和进行性肺损伤NP。这项研究表明，一次吸入In ₂ O ₃ NP会导致肺损伤恶化，例如PAP，慢性活动性炎症，泡沫巨噬细胞浸润和肉芽肿。即使在非常低的剂量（7.5 cm ² /大鼠）下，PAP的早期发作和持续性也意味着迫切需要重新评估In ₂ O ₃ NP的职业推荐暴露极限，以保护工人。