Aerosol Toxicology Research Center, HCTm CO.,LTD, Icheon, South Korea.
Department of Mechanical Engineering, Hanyang University, Ansan, South Korea.
Part Fibre Toxicol. 2020 Oct 20;17(1):54. doi: 10.1186/s12989-020-00384-w.
Information on particle deposition, retention, and clearance is important when evaluating the risk of inhaled nanomaterials to human health. The revised Organization Economic Cooperation and Development (OECD) inhalation toxicity test guidelines now require lung burden measurements of nanomaterials after rodent subacute and sub-chronic inhalation exposure (OECD 412, OECD 413) to inform on lung clearance behavior and translocation after exposure and during post-exposure observation (PEO). Lung burden measurements are particularly relevant when the testing chemical is a solid poorly soluble nanomaterial. Previously, the current authors showed that total retained lung burden of inhaled soluble silver nanoparticles (AgNPs) could be effectively measured using any individual lung lobe.
Accordingly, the current study investigated the evenness of deposition/retention of poorly soluble gold nanoparticles (AuNPs) after 1 and 5 days of inhalation exposure. Rats were exposed nose-only for 1 or 5 days (6 h/day) to an aerosol of 11 nm well-dispersed AuNPs. Thereafter, the five lung lobes were separated and the gold concentrations measured using an inductively coupled plasma-mass spectrophotometer (ICP-MS). The results showed no statistically significant difference in the AuNP deposition/retention among the different lung lobes in terms of the gold mass per gram of lung tissue.
Thus, it would seem that any rat lung lobe can be used for the lung burden analysis after short or long-term NP inhalation, while the other lobes can be used for collecting and analyzing the bronchoalveolar lavage fluid (BALF) and for the histopathological analysis. Therefore, combining the lung burden measurement, histopathological tissue preparation, and BALF assay from one rat can minimize the number of animals used and maximize the number of endpoints measured.
在评估吸入纳米材料对人类健康的风险时，有关颗粒沉积、保留和清除的信息非常重要。修订后的经济合作与发展组织（OECD）吸入毒性测试指南现在要求在啮齿动物亚急性和亚慢性吸入暴露后（OECD 412、OECD 413）测量纳米材料的肺部负担，以了解暴露后和暴露后观察期间（PEO）的肺部清除行为和转移。当测试化学品是固体难溶性纳米材料时，肺部负担测量尤为重要。此前，作者研究组表明，可使用任意单个肺叶有效测量吸入可溶性银纳米颗粒（AgNPs）的总保留肺部负担。
因此，本研究调查了吸入 11nm 分散良好的 AuNPs1 或 5 天后，肺部难溶性金纳米颗粒（AuNPs）沉积/保留的均匀性。大鼠经鼻仅暴露于气溶胶中 1 或 5 天（6h/d），每天接触 11nm 分散良好的 AuNPs。然后将五个肺叶分开，并用电感耦合等离子体质谱仪（ICP-MS）测量金浓度。结果表明，就每克肺组织中的金质量而言，不同肺叶之间的 AuNP 沉积/保留没有统计学上的显著差异。
因此，似乎可以在短期或长期 NP 吸入后使用任何大鼠肺叶进行肺部负担分析，而其他肺叶可用于收集和分析支气管肺泡灌洗液（BALF）以及进行组织病理学分析。因此，从一只大鼠中同时进行肺部负担测量、组织病理学准备和 BALF 分析，可以最大限度地减少使用的动物数量并最大限度地增加测量的终点数量。
