Abstract

No detailed information on in vivo 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 > lymph nodes > hard bone > liver > 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.

摘要

没有关于慢性低剂量吸入后CeO ₂纳米颗粒（NPs）体内生物动力学的详细信息。根据OECD TG453对雌性Wistar大鼠进行的长期全身吸入研究确定了肺，与肺相关的淋巴结以及主要的非肺器官，血液和粪便中CeO _2的负担（每天6小时，每周5天，持续104周，浓度如下：0、0.1、0.3、1.0和3.0 mg / m ³，在3、12、24个月后处死动物。不同的光谱方法（ICP-MS，离子束显微镜）用于定量器官负荷和可视化组织中的NP分布模式。暴露24个月后，CeO ₂最高肺负荷（每肺4.41毫克）与最高的气溶胶浓度相关，而其他组的剂量依赖性则成比例地降低。成像技术证实了肺组织内存在不同大小类别的CeO ₂团块，且分布不均匀。对于最高暴露组，在本研究分析的器官和组织中，除淋巴结和骨骼外，在24个月后总共发现了保留在肺中的1.2％剂量。首席执行官₂每个组织的负担从肺>淋巴结>硬骨>肝>骨髓减少。对于两个剂量组，肝器官负荷显示出较低的蓄积率。在这里，肝脏可以看作是仓库，而肾脏，骨骼和骨髓似乎是垃圾场，因为随着时间的推移，NP负担不断增加。