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吸入纳米氧化铈在 2 年低剂量暴露研究中的器官负担:是“垃圾库”还是“储库”?

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

机构信息

Department of Chemicals and Product Safety, German Federal Institute of Risk Assessment (BfR), Berlin, Germany.

Institute of Medical Physics and Biophysics, Leipzig University, Leipzig, Germany.

出版信息

Nanotoxicology. 2020 May;14(4):554-576. doi: 10.1080/17435390.2020.1736355. Epub 2020 Mar 27.

Abstract

No detailed information on biokinetics of CeO nanoparticles (NPs) following chronic low-dose inhalation is available. The CeO 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/m, 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 CeO 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 CeO 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 CeO 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

目前尚无关于 CeO 纳米颗粒(NPs)经慢性低剂量吸入后的生物动力学的详细信息。根据 OECD TG453 进行的一项雌性 Wistar 大鼠慢性全身吸入研究中,确定了 CeO 在肺部、肺相关淋巴结和主要非肺部器官、血液和粪便中的负荷,该研究每天进行 6 小时,每周 5 天,共 104 周,浓度分别为:0、0.1、0.3、1.0 和 3.0mg/m,动物在 3、12 和 24 个月后被处死。使用不同的光谱方法(ICP-MS、离子束显微镜)对器官负荷进行定量,并对组织中 NP 分布模式进行可视化。暴露 24 个月后,最高的 CeO 肺部负荷(每肺 4.41mg)与最高的气溶胶浓度相关,并且与其他组呈剂量依赖性,比例降低。成像技术证实了 CeO 团聚体在肺部组织中存在不同大小类别的存在,分布不均匀。对于最高暴露组,在总共 24 个月的时间里,在本研究中分析的器官和组织中发现,保留在肺部的剂量为 1.2%,不包括淋巴结和骨骼。每组织的 CeO 负荷从肺部>淋巴结>硬骨>肝脏>骨髓减少。对于两个剂量组,肝脏器官负荷显示出低积累率。在这里,肝脏可以被视为储存库,而肾脏、骨骼和骨髓似乎由于 NP 负荷随时间的推移而不断增加而成为倾倒区。

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