Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats.
Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats.
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DOI：
10.1186/1743-8977-11-30
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发表时间：
2014-07-03
影响因子：
10
通讯作者：
de Jong WH
中科院分区：
文献类型：
--
作者：
Geraets L;Oomen AG;Krystek P;Jacobsen NR;Wallin H;Laurentie M;Verharen HW;Brandon EF;de Jong WH
本研究的目的是获得可用于二氧化钛纳米材料人体风险评估的动力学数据。各种二氧化钛纳米粒子（NM-100、NM-101、NM-102、NM-103 和 NM-104）的组织分布和血液动力学在大鼠中口服和静脉注射单次或五次重复剂量后长达 90 天进行了研究，这些纳米粒子的初级粒径、晶型和疏水性各不相同。对于口腔研究，选择肝脏、脾脏和肠系膜淋巴结作为钛（Ti）分析的靶组织。仅部分大鼠肝脏和脾脏中的 Ti 水平高于检测限。在肠系膜淋巴结中可以检测到低水平的钛。这些结果表明，胃肠道中发生了一些轻微的吸收，但程度非常有限。单次和重复静脉（IV）暴露后，钛迅速从体循环分布到所有评估的组织（即肝、脾、肾、肺、心、脑、胸腺、生殖器官）。肝脏被确定为主要靶组织，其次是脾脏和肺。在单次或重复暴露后 24 小时测量的所有四种测试纳米材料的总回收率（以标称剂量的百分比表示）对于雄性或雌性动物分别为 64-95% 或 59-108%。在暴露后 90 天期间，观察到 Ti 水平有所下降（主要是 NM-100 和 NM-102），最大相对下降量为 26%。动力学分析的结果也证实了这一点，该分析表明，对于每种研究的组织，半衰期都很长（范围为 28-650 天，取决于 TiO2 颗粒和研究的组织）。在不同颗粒之间观察到动力学曲线的微小差异，尽管这些差异不能与初级颗粒尺寸或疏水性的差异清楚地相关。观察到晶型（锐钛矿与金红石）对总钛回收率的影响的一些迹象。总体而言，目前的口服和静脉注射研究的结果表明口服生物利用度非常低且组织消除缓慢。有限的吸收加上缓慢的消除可能会导致长期潜在的组织积累。
The aim of this study was to obtain kinetic data that can be used in human risk assessment of titanium dioxide nanomaterials. Tissue distribution and blood kinetics of various titanium dioxide nanoparticles (NM-100, NM-101, NM-102, NM-103, and NM-104), which differ with respect to primary particle size, crystalline form and hydrophobicity, were investigated in rats up to 90 days post-exposure after oral and intravenous administration of a single or five repeated doses. For the oral study, liver, spleen and mesenteric lymph nodes were selected as target tissues for titanium (Ti) analysis. Ti-levels in liver and spleen were above the detection limit only in some rats. Titanium could be detected at low levels in mesenteric lymph nodes. These results indicate that some minor absorption occurs in the gastrointestinal tract, but to a very limited extent. Both after single and repeated intravenous (IV) exposure, titanium rapidly distributed from the systemic circulation to all tissues evaluated (i.e. liver, spleen, kidney, lung, heart, brain, thymus, reproductive organs). Liver was identified as the main target tissue, followed by spleen and lung. Total recovery (expressed as % of nominal dose) for all four tested nanomaterials measured 24 h after single or repeated exposure ranged from 64-95% or 59-108% for male or female animals, respectively. During the 90 days post-exposure period, some decrease in Ti-levels was observed (mainly for NM-100 and NM-102) with a maximum relative decrease of 26%. This was also confirmed by the results of the kinetic analysis which revealed that for each of the investigated tissues the half-lifes were considerable (range 28–650 days, depending on the TiO2-particle and tissue investigated). Minor differences in kinetic profile were observed between the various particles, though these could not be clearly related to differences in primary particle size or hydrophobicity. Some indications were observed for an effect of crystalline form (anatase vs. rutile) on total Ti recovery. Overall, the results of the present oral and IV study indicates very low oral bioavailability and slow tissue elimination. Limited uptake in combination with slow elimination might result in the long run in potential tissue accumulation.
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影响因子：
10
作者：
Jacobsen NR;Møller P;Jensen KA;Vogel U;Ladefoged O;Loft S;Wallin H
通讯作者：
Wallin H
DOI：
10.1111/j.1467-2494.1997.tb00175.x
发表时间：
1997-01-01
影响因子：
2.3
作者：
Dussert, A.-S.;Gooris, E.;Hemmerle, J.
通讯作者：
Hemmerle, J.
影响因子：
5
作者：
Shinohara, Naohide;Danno, Nobuko;Gamo, Masashi
通讯作者：
Gamo, Masashi
影响因子：
5.5
作者：
Lankveld, Danielle P. K.;Rayavarapu, Raja G.;Manohar, Srirang
通讯作者：
Manohar, Srirang
影响因子：
10
作者：
Johnston HJ;Hutchison GR;Christensen FM;Peters S;Hankin S;Stone V
通讯作者：
Stone V