Nanomaterial (NM) characteristics may affect the pulmonary toxicity and inflammatory response, including specific surface area, size, shape, crystal phase or other surface characteristics. Grouping of TiO2 in hazard assessment might be challenging because of variation in physicochemical properties. We exposed C57BL/6 J mice to a single dose of four anatase TiO2 NMs with various sizes and shapes by intratracheal instillation and assessed the pulmonary toxicity 1, 3, 28, 90 or 180 days post-exposure. The quartz DQ12 was included as benchmark particle. Pulmonary responses were evaluated by histopathology, electron microscopy, bronchoalveolar lavage (BAL) fluid cell composition and acute phase response. Genotoxicity was evaluated by DNA strand break levels in BAL cells, lung and liver in the comet assay. Multiple regression analyses were applied to identify specific TiO2 NMs properties important for the pulmonary inflammation and acute phase response. The TiO2 NMs induced similar inflammatory responses when surface area was used as dose metrics, although inflammatory and acute phase response was greatest and more persistent for the TiO2 tube. Similar histopathological changes were observed for the TiO2 tube and DQ12 including pulmonary alveolar proteinosis indicating profound effects related to the tube shape. Comparison with previously published data on rutile TiO2 NMs indicated that rutile TiO2 NMs were more inflammogenic in terms of neutrophil influx than anatase TiO2 NMs when normalized to total deposited surface area. Overall, the results suggest that specific surface area, crystal phase and shape of TiO2 NMs are important predictors for the observed pulmonary effects of TiO2 NMs.

中文翻译：

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TiO2纳米材料的理化性质对气管内暴露小鼠的肺部炎症，急性期反应和肺泡蛋白沉着的影响。

纳米材料（NM）的特性可能会影响肺部毒性和炎症反应，包括比表面积，大小，形状，晶相或其他表面特性。由于物理化学性质的变化，在危害评估中将TiO2分组可能具有挑战性。我们通过气管内滴注将C57BL / 6 J小鼠暴露于单剂量的四个大小和形状各异的锐钛矿型TiO2 NMs中，并评估了暴露后1、3、28、90或180天的肺毒性。石英DQ12作为基准粒子被包括在内。通过组织病理学，电子显微镜，支气管肺泡灌洗（BAL）液细胞组成和急性期反应评估肺反应。在彗星试验中，通过BAL细胞，肺和肝中DNA链断裂水平评估了遗传毒性。应用多元回归分析确定对肺部炎症和急性期反应重要的特定TiO2 NMs特性。当将表面积用作剂量指标时，TiO2 NMs诱导了类似的炎症反应，尽管对于TiO2管来说，炎症和急性期反应最大且更持久。对于TiO2管和DQ12（包括肺泡蛋白沉着症）也观察到了相似的组织病理学变化，表明与管形状有关的深远影响。与先前发表的有关金红石型TiO2 NMs的数据比较表明，就中性粒细胞流入而言，金红石型TiO2 NMs比锐钛矿型TiO2 NMs更具致火性，并按总沉积表面积进行归一化处理。总体而言，结果表明比表面积，