Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
Arch Toxicol. 2012 Jul;86(7):1117-22. doi: 10.1007/s00204-012-0833-3. Epub 2012 Mar 15.
After deposition in the respiratory tract, nanoparticles exhibit acute, neutrophil-driven inflammatory and oxidative reactions, fibrotic responses and in chronic studies under overload conditions carcinogenic effects, more severely than the microscaled materials of the same chemistry. Besides these effects also known to be induced by microsized particles, nanoparticles principally can translocate from the site of exposure to circulation and become systemically available. This may either increase the toxic outcome (e.g. cardio-vascular effects and potential responses in remote organs) or facilitate an elimination of nanomaterials. For example, in combination with partial dissolution, a strong lung response after a short-term inhalative exposure may be followed by a rapid recovery effect. Mechanistically, in vitro and in vivo tests demonstrated that nanoparticles induce inflammation and oxidative stress after interaction with macrophages and lung epithelial cells; consequently, a cytotoxic and genotoxic potential may exist. The deposition, retention and clearance behaviour of inhaled nanomaterials and the toxic effects observed are decisively dependent on the particle agglomeration status of the aerosol. Two principally different experimental approaches are used for inhalative exposure to nanoparticles: either (1) a basic research-oriented approach using very small aerosol mass concentrations or particle formulations that result in at least partially nanoscaled aerosols; in this way, the potential hazard and the translocation potential for individual nanoparticles can be followed effectively; or (2) exposure scenarios mimicking the occupational situation (risk-oriented) with mostly agglomerated nanoparticles; consequently, the probable risk deriving from incidental/accidental exposure can be assessed more adequately.
纳米颗粒在呼吸道沉积后，会引发急性、嗜中性粒细胞驱动的炎症和氧化反应、纤维化反应，在超负荷条件下的慢性研究中还会引发致癌作用，其严重程度超过了相同化学物质的微尺度材料。除了已知由微尺度颗粒引起的这些作用之外，纳米颗粒还可以从暴露部位转移到循环系统中，并变得全身可用。这可能会增加毒性作用（例如心血管效应和远程器官的潜在反应），或者促进纳米材料的消除。例如，在与部分溶解结合的情况下，短期吸入暴露后强烈的肺部反应可能会随后出现快速恢复效应。在机制上，体外和体内试验表明，纳米颗粒与巨噬细胞和肺上皮细胞相互作用后会引发炎症和氧化应激；因此，可能存在细胞毒性和遗传毒性潜力。吸入纳米材料的沉积、保留和清除行为以及观察到的毒性作用，在很大程度上取决于气溶胶中颗粒团聚状态。有两种主要不同的实验方法可用于纳米颗粒的吸入暴露：（1）使用非常小的气溶胶质量浓度或至少部分纳米尺度气溶胶的颗粒配方的基础研究导向方法；通过这种方式，可以有效地跟踪单个纳米颗粒的潜在危害和转移潜力；或（2）模拟职业情况（风险导向）的暴露场景，其中主要是团聚的纳米颗粒；因此，可以更充分地评估偶然/意外暴露所带来的可能风险。
