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.

目前尚无关于二氧化铈（CeO₂）纳米颗粒（NPs）经慢性低剂量吸入染毒后的体内（in vivo）生物动力学的详细研究数据。本研究依据经济合作与发展组织试验指南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，设置0、0.1、0.3、1.0及3.0 mg/m³共5个暴露浓度，分别于染毒3、12、24个月后处死动物；并测定了肺、肺相关淋巴结、主要非肺部器官、血液及粪便中的CeO₂负载量。本研究采用多种光谱学方法（电感耦合等离子体质谱法（ICP-MS）、离子束显微镜）对器官内的CeO₂负载量进行定量分析，并可视化纳米颗粒在组织内的分布模式。染毒24个月后，气溶胶浓度最高组的肺CeO₂负载量达峰值（每肺4.41 mg），其余各组的负载量随暴露浓度降低呈比例下降，整体呈现剂量依赖关系。成像技术证实，肺组织内存在不同粒径的CeO₂团聚体，且分布不均一。对于最高暴露浓度组，染毒24个月后，本研究检测的器官与组织（不含淋巴结与骨骼）中留存的CeO₂总量占肺部滞留剂量的1.2%。各组织的CeO₂负载量由高到低依次为：肺＞淋巴结＞致密骨＞肝脏＞骨髓。针对两个剂量组，肝脏的CeO₂负载量积累速率较低，因此肝脏可被视为储存库；而肾脏、骨骼与骨髓的纳米颗粒负载量随时间持续升高，似乎为长期蓄积部位。