There is a steadily increasing quantity of silver nanoparticles (AgNP) produced for numerous industrial, medicinal and private purposes, leading to an increased risk of inhalation exposure for both professionals and consumers. Particle inhalation can result in inflammatory and allergic responses, and there are concerns about other negative health effects from either acute or chronic low-dose exposure. To study the fate of inhaled AgNP, healthy adult rats were exposed to 1½-hour intra-tracheal inhalations of pristine 105Ag-radiolabeled, 20 nm AgNP aerosols (with mean doses across all rats of each exposure group of deposited NP-mass and NP-number being 13.5 ± 3.6 μg, 7.9 ± 3.2•1011, respectively). At five time-points (0.75 h, 4 h, 24 h, 7d, 28d) post-exposure (p.e.), a complete balance of the [105Ag]AgNP fate and its degradation products were quantified in organs, tissues, carcass, lavage and body fluids, including excretions. Rapid dissolution of [105Ag]Ag-ions from the [105Ag]AgNP surface was apparent together with both fast particulate airway clearance and long-term particulate clearance from the alveolar region to the larynx. The results are compatible with evidence from the literature that the released [105Ag]Ag-ions precipitate rapidly to low-solubility [105Ag]Ag-salts in the ion-rich epithelial lining lung fluid (ELF) and blood. Based on the existing literature, the degradation products rapidly translocate across the air-blood-barrier (ABB) into the blood and are eliminated via the liver and gall-bladder into the small intestine for fecal excretion. The pathway of [105Ag]Ag-salt precipitates was compatible with auxiliary biokinetics studies at 24 h and 7 days after either intravenous injection or intratracheal or oral instillation of [110mAg]AgNO3 solutions in sentinel groups of rats. However, dissolution of [105Ag]Ag-ions appeared not to be complete after a few hours or days but continued over two weeks p.e. This was due to the additional formation of salt layers on the [105Ag]AgNP surface that mediate and prolonge the dissolution process. The concurrent clearance of persistent cores of [105Ag]AgNP and [105Ag]Ag-salt precipitates results in the elimination of a fraction > 0.8 (per ILD) after one week, each particulate Ag-species accounting for about half of this. After 28 days p.e. the cleared fraction rises marginally to 0.94 while 2/3 of the remaining [105Ag]AgNP are retained in the lungs and 1/3 in secondary organs and tissues with an unknown partition of the Ag species involved. However, making use of our previous biokinetics studies of poorly soluble [195Au]AuNP of the same size and under identical experimental and exposure conditions (Kreyling et al., ACS Nano 2018), the kinetics of the ABB-translocation of [105Ag]Ag-salt precipitates was estimated to reach a fractional maximum of 0.12 at day 3 p.e. and became undetectable 16 days p.e. Hence, persistent cores of [105Ag]AgNP were cleared throughout the study period. Urinary [105Ag]Ag excretion is minimal, finally accumulating to 0.016. The biokinetics of inhaled [105Ag]AgNP is relatively complex since the dissolving [105Ag]Ag-ions (a) form salt layers on the [105Ag]AgNP surface which retard dissolution and (b) the [105Ag]Ag-ions released from the [105Ag]AgNP surface form poorly-soluble precipitates of [105Ag]Ag-salts in ELF. Therefore, hardly any [105Ag]Ag-ion clearance occurs from the lungs but instead [105Ag]AgNP and nano-sized precipitated [105Ag]Ag-salt are cleared via the larynx into GIT and, in addition, via blood, liver, gall bladder into GIT with one common excretional pathway via feces out of the body.

中文翻译：

---

吸入1.5小时后，在成年健康大鼠中28天新鲜产生的原始20 nm银纳米颗粒气溶胶的定量生物动力学。

用于许多工业，医学和私人目的的银纳米颗粒（AgNP）的数量稳定增长，这导致专业人员和消费者吸入接触的风险增加。吸入颗粒会导致发炎和过敏反应，并且人们担心急性或慢性低剂量暴露会对健康产生其他负面影响。为了研究吸入AgNP的命运，健康成年大鼠在气管内吸入原始105Ag放射性标记的20 nm AgNP气雾剂进行了1.5小时的气管吸入（平均剂量为每个沉积组NP-质量和NP-暴露组的所有大鼠的平均剂量）分别为13.5±3.6μg，7.9±3.2•1011）。在暴露后（pe）的五个时间点（0.75小时，4小时，24小时，7天，28天），在器官，组织，屠体，灌洗液和包括排泄物在内的体液中定量分析了[105Ag] AgNP命运及其降解产物的完全平衡。从[105Ag] AgNP表面迅速溶解[105Ag] Ag离子与快速的气道清除和从肺泡区到喉部的长期颗粒清除都很明显。该结果与文献证据相符，即所释放的[105Ag] Ag离子在富含离子的上皮衬里肺液（ELF）和血液中迅速沉淀为低溶解度[105Ag] Ag盐。根据现有文献，降解产物迅速通过气血屏障（ABB）转移到血液中，并通过肝脏和胆囊排入小肠排泄粪便。在大鼠前哨组静脉注射或气管内或口服滴注[110mAg] AgNO3溶液后的24小时和7天，[105Ag] Ag-盐沉淀的途径与辅助生物动力学研究兼容。但是，[105Ag] Ag离子的溶解似乎在数小时或数天后仍未完成，但持续了两周之久。这是由于[105Ag] AgNP表面上形成了另外的盐层，这些盐层介导并延长了溶解时间处理。[105Ag] AgNP和[105Ag] Ag-盐沉淀物的持久核的同时清除导致一周后消除了大于0.8（每个ILD）的馏分，每种颗粒的Ag种类约占其中的一半。pe 28天后，清除的分数小幅上升到0。94，而剩余的[105Ag] AgNP中有2/3保留在肺中，而次要器官和组织中保留了1/3，涉及的Ag种类未知。但是，利用我们先前对相同大小，在相同实验和暴露条件下难溶的[195Au] AuNP进行的生物动力学研究（Kreyling等人，ACS Nano 2018），[105Ag] Ag的ABB易位动力学盐沉淀物估计在第3天pe达到最大分数0.12，在16 pe时变得不可检测。因此，在整个研究期间清除了[105Ag] AgNP的持久核心。尿中[105Ag] Ag的排泄量极少，最终累积至0.016。吸入的[105Ag] AgNP的生物动力学相对复杂，因为溶解的[105Ag] Ag离子（a）在[105Ag] AgNP表面上形成了盐层，从而阻碍了溶解，并且（b）从[105Ag] AgNP释放出的[105Ag] Ag离子。 [105Ag] AgNP表面在ELF中形成[105Ag] Ag盐的难溶沉淀物。因此，几乎没有[105Ag] Ag离子从肺中清除，而是[105Ag] AgNP和纳米级沉淀的[105Ag] Ag-盐通过喉部进入GIT，此外还通过血液，肝脏，胆汁清除。膀胱通过粪便通过一种常见的排泄途径进入GIT。