Senoh Hideki, Suzuki Masaaki, Kano Hirokazu, Kasai Tatsuya, Fukushima Shoji
National Institute of Occupational Safety and Health, Japan Organization of Occupational Health and Safety, Fujisawa 251-8555, Kanagawa, Japan.
National Institute of Occupational Safety and Health, Japan Organization of Occupational Health and Safety, Kawasaki 214-8585, Kanagawa, Japan.
Nanomaterials (Basel). 2024 Dec 16;14(24):2019. doi: 10.3390/nano14242019.
The purpose of the present study is to contribute to the establishment of a standard method for evaluating the adverse effects of nanomaterials by intratracheal administration. Low and high doses of multi-walled carbon nanotubes (MWCNTs) were administered to rats in a single administration or the same final dose as the single administration but divided over four administrations. Bronchoalveolar lavage examination on day 14 showed an inflammatory reaction and cytotoxicity in the lung, generally greater at the higher dose, and tending to be greater in the rats with four administrations at both the low and high doses. Histopathologic findings showed increased alveolar macrophages and MWCNT deposition (fibers phagocytosed by alveolar macrophages and fibers that were not phagocytosed) in the alveolar space, granulomatous changes, and MWCNT deposition in bronchus-associated lymphoid tissue (BALT) and lung-related lymph nodes on days 14, 28, and 91. In addition, alveolar type II epithelial hyperplasia was observed on day 91, and fibrosis of the alveolar wall was observed on days 28 and 91. Fewer alveolar macrophages with phagocytosed MWCNTs were present at day 91 compared to day 28. MWCNT deposition tended to be higher in the BALT after a single administration, whereas deposition was higher in the lung-related lymph nodes after four administrations. MWCNTs were considered to be transported from the lungs or BALT to the lymph nodes over time. There were no significant differences in MWCNT deposition in the lung after the single administration compared with four administrations at either the low or high doses, and the histopathological findings were similar after single and four administrations, at both the low and high doses. Based on the above findings, a toxicity evaluation of the nanomaterials can be sufficiently performed by intratracheal administration, even with a single intratracheal administration.
本研究的目的是为建立一种通过气管内给药评估纳米材料不良反应的标准方法做出贡献。将低剂量和高剂量的多壁碳纳米管（MWCNT）以单次给药的方式给予大鼠，或者给予与单次给药相同的最终剂量，但分四次给药。第14天的支气管肺泡灌洗检查显示肺部有炎症反应和细胞毒性，一般在高剂量时更明显，并且在低剂量和高剂量下，四次给药的大鼠的炎症反应和细胞毒性往往更大。组织病理学检查结果显示，在第14天、28天和91天时，肺泡腔中的肺泡巨噬细胞增多和MWCNT沉积（被肺泡巨噬细胞吞噬的纤维和未被吞噬的纤维）、肉芽肿性变化以及支气管相关淋巴组织（BALT）和肺相关淋巴结中的MWCNT沉积。此外，在第91天时观察到II型肺泡上皮增生，在第28天和91天时观察到肺泡壁纤维化。与第28天相比，第91天时吞噬MWCNT的肺泡巨噬细胞较少。单次给药后，BALT中的MWCNT沉积往往更高，而四次给药后，肺相关淋巴结中的沉积更高。随着时间的推移，MWCNT被认为是从肺或BALT转运到淋巴结的。在低剂量或高剂量下，单次给药后肺中MWCNT的沉积与四次给药后相比无显著差异，并且在低剂量和高剂量下，单次给药和四次给药后的组织病理学检查结果相似。基于上述发现，即使仅进行一次气管内给药，也可以通过气管内给药充分进行纳米材料的毒性评估。
