Kobayashi Norihiro, Naya Masato, Endoh Shigehisa, Maru Junko, Yamamoto Kazuhiro, Nakanishi Junko
Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8569, Japan.
Toxicology. 2009 Oct 1;264(1-2):110-8. doi: 10.1016/j.tox.2009.08.002. Epub 2009 Aug 8.
Two intratracheal instillation experiments with nano-size titanium dioxide (TiO(2)) particles of different sizes and agglomerations were conducted in rats to compare the biological responses induced by the different particles. In experiment 1, 5 mg/kg of nano-TiO(2) particles of different primary sizes was intratracheally instilled in rats. In experiment 2, a similar procedure was followed with 5 mg/kg of nano-TiO(2) particles of the same primary sizes but different agglomerations in liquid. Following the instillations, body and lung weight measurements, bronchoalveolar fluid (BALF) cells and inflammatory biomarkers assessment, and histopathological evaluations of the lungs and other tissues were conducted. Pulmonary inflammatory responses until 1 week post-instillation differed among the TiO(2) particle-exposed groups: that is, smaller particles induced greater inflammation in the short-term observations. With regard to the long-term effects (>1 week post-instillation), however, pulmonary inflammation remarkably recovered in all the TiO(2) particle-exposed groups, with no differences between the groups regardless of particle size. On the other hand, no clear relationship was observed between the TiO(2) particle-exposed groups with different agglomerations but the same primary size. These findings suggest that different evaluations can be derived on the basis of the observations up to 1 week post-instillation and those after 1 month post-instillation. In most of the current studies, the relationship between pulmonary responses and instilled particle sizes has been discussed only on the basis of the 24 h post-instillation results, which could be a misleading evaluation. Consequently, our findings indicate that both short- and long-term effects should be evaluated when assessing the toxicity of nanoparticles based on the results of intratracheal instillation studies.
在大鼠中进行了两项气管内滴注实验，使用不同尺寸和团聚状态的纳米级二氧化钛（TiO₂）颗粒，以比较不同颗粒诱导的生物学反应。在实验1中，将5mg/kg不同原始尺寸的纳米TiO₂颗粒气管内滴注到大鼠体内。在实验2中，采用类似的程序，使用5mg/kg相同原始尺寸但在液体中有不同团聚状态的纳米TiO₂颗粒。滴注后，测量了体重和肺重量，评估了支气管肺泡灌洗液（BALF）细胞和炎症生物标志物，并对肺和其他组织进行了组织病理学评估。在滴注后1周内，TiO₂颗粒暴露组的肺部炎症反应有所不同：即在短期观察中，较小的颗粒诱导了更大的炎症。然而，关于长期影响（滴注后>1周），所有TiO₂颗粒暴露组的肺部炎症都显著恢复，无论颗粒大小，各组之间均无差异。另一方面，在具有相同原始尺寸但不同团聚状态的TiO₂颗粒暴露组之间未观察到明确的关系。这些发现表明，根据滴注后1周内的观察结果和滴注后1个月后的观察结果，可以得出不同的评估。在目前的大多数研究中，仅根据滴注后24小时的结果讨论了肺部反应与滴注颗粒大小之间的关系，这可能是一种误导性的评估。因此，我们的研究结果表明，在基于气管内滴注研究结果评估纳米颗粒的毒性时，应同时评估短期和长期影响。
Zotero 插件