Organ burden of inhaled nanoceria in a 2-year low-dose exposure study: dump or depot?

No detailed information on <i>in vivo</i> biokinetics of CeO₂ nanoparticles (NPs) following chronic low-dose inhalation is available. The CeO₂ burden for lung, lung-associated lymph nodes, and major non-pulmonary organs, blood, and feces, was determined in a chronic whole-body inhalation study in female Wistar rats undertaken according to OECD TG453 (6 h per day for 5 days per week for a 104 weeks with the following concentrations: 0, 0.1, 0.3, 1.0, and 3.0 mg/m³, animals were sacrificed after 3, 12, 24 months). Different spectroscopy methods (ICP-MS, ion-beam-microscopy) were used for the quantification of organ burden and for visualization of NP distribution patterns in tissues. After 24 months of exposure, the highest CeO₂ lung burden (4.41 mg per lung) was associated with the highest aerosol concentration and was proportionally lower for the other groups in a dose-dependent manner. Imaging techniques confirmed the presence of CeO₂ agglomerates of different size categories within lung tissue with a non-homogenous distribution. For the highest exposure group, after 24 months in total 1.2% of the dose retained in the lung was found in the organs and tissues analyzed in this study, excluding lymph nodes and skeleton. The CeO₂ burden per tissue decreased from lungs &gt; lymph nodes &gt; hard bone &gt; liver &gt; bone marrow. For two dosage groups, the liver organ burden showed a low accumulation rate. Here, the liver can be regarded as depot, whereas kidneys, the skeleton, and bone marrow seem to be dumps due to steadily increasing NP burden over time.目前尚无关于慢性低剂量吸入二氧化铈（CeO₂）纳米颗粒（NPs）的体内（in vivo）生物动力学的详细研究资料。本研究按照经济合作与发展组织实验指南453（OECD TG453），对雌性Wistar大鼠开展慢性全身吸入染毒实验：每日染毒6小时，每周5天，持续104周，染毒浓度分别设置为0、0.1、0.3、1.0及3.0 mg/m³，分别于染毒3、12、24个月后处死实验动物。本研究测定了肺、肺相关淋巴结、主要非肺器官、血液及粪便中的二氧化铈负荷量，并采用电感耦合等离子体质谱（ICP-MS）、离子束显微镜等多种光谱学方法对器官负荷量进行定量分析，同时可视化观察组织内纳米颗粒的分布模式。染毒24个月后，最高气溶胶浓度组的肺二氧化铈负荷量达峰值（每肺4.41 mg），其余各组的负荷量随染毒剂量升高呈比例递增的剂量依赖性变化趋势，且均低于该最高浓度组。成像技术证实，肺组织内存在不同粒径级别的二氧化铈团聚体，且分布呈非均质性。对于最高暴露组，染毒24个月后，本研究分析的器官与组织中，肺部滞留剂量的总占比为1.2%（不含淋巴结与骨骼）。各组织的二氧化铈负荷量依次为：肺＞淋巴结＞硬骨＞肝脏＞骨髓。在两个剂量组中，肝脏的二氧化铈蓄积率较低，可将肝脏视为二氧化铈的储存库；而肾脏、骨骼与骨髓的纳米颗粒负荷量随时间持续升高，因此被视为二氧化铈的滞留蓄积部位。