Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST), 505 Boul, De Maisonneuve Ouest, Montréal, Québec H3A 3C2, Canada.
Part Fibre Toxicol. 2013 Oct 4;10:48. doi: 10.1186/1743-8977-10-48.
The exact role of primary nanoparticle (NP) size and their degree of agglomeration in aerosols on the determination of pulmonary effects is still poorly understood. Smaller NP are thought to have greater biological reactivity, but their level of agglomeration in an aerosol may also have an impact on pulmonary response. The aim of this study was to investigate the role of primary NP size and the agglomeration state in aerosols, using well-characterized TiO₂ NP, on their relative pulmonary toxicity, through inflammatory, cytotoxic and oxidative stress effects in Fisher 344 male rats.
Three different sizes of TiO₂ NP, i.e., 5, 10-30 or 50 nm, were inhaled as small (SA) (< 100 nm) or large agglomerates (LA) (> 100 nm) at 20 mg/m³ for 6 hours.
Compared to the controls, bronchoalveolar lavage fluids (BALF) showed that LA aerosols induced an acute inflammatory response, characterized by a significant increase in the number of neutrophils, while SA aerosols produced significant oxidative stress damages and cytotoxicity. Data also demonstrate that for an agglomeration state smaller than 100 nm, the 5 nm particles caused a significant increase in cytotoxic effects compared to controls (assessed by an increase in LDH activity), while oxidative damage measured by 8-isoprostane concentration was less when compared to 10-30 and 50 nm particles. In both SA and LA aerosols, the 10-30 nm TiO₂ NP size induced the most pronounced pro-inflammatory effects compared to controls.
Overall, this study showed that initial NP size and agglomeration state are key determinants of nano-TiO₂ lung inflammatory reaction, cytotoxic and oxidative stress induced effects.
初级纳米颗粒（NP）的大小及其在气溶胶中的团聚程度对确定肺部效应的确切作用仍知之甚少。人们认为较小的 NP 具有更大的生物反应性，但它们在气溶胶中的团聚程度也可能对肺部反应产生影响。本研究旨在通过 Fisher 344 雄性大鼠的炎症、细胞毒性和氧化应激效应，研究具有良好特征的 TiO₂ NP 的初级 NP 大小和团聚状态在气溶胶中的作用，及其相对肺毒性。
三种不同大小的 TiO₂ NP，即 5、10-30 或 50nm，以小（SA）（<100nm）或大团聚体（LA）（>100nm）的形式在 20mg/m³下吸入 6 小时。
与对照组相比，支气管肺泡灌洗液（BALF）显示 LA 气溶胶诱导急性炎症反应，特征是中性粒细胞数量显著增加，而 SA 气溶胶产生显著氧化应激损伤和细胞毒性。数据还表明，对于小于 100nm 的团聚状态，与对照组相比，5nm 颗粒引起的细胞毒性作用显著增加（通过 LDH 活性增加来评估），而与 10-30nm 和 50nm 颗粒相比，8-异前列腺素浓度测量的氧化损伤较少。在 SA 和 LA 气溶胶中，与对照组相比，10-30nm TiO₂ NP 尺寸引起的促炎作用最为明显。
总的来说，这项研究表明，初始 NP 大小和团聚状态是纳米 TiO₂ 肺部炎症反应、细胞毒性和氧化应激诱导效应的关键决定因素。
