Industrially produced quantities of TiO2 nanoparticles are steadily rising, leading to an increasing 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 TiO2-NP, adult rats were exposed to 2-h intra-tracheal inhalations of 48V-radiolabeled, 20 nm TiO2-NP aerosols (deposited NP-mass 1.4 ± 0.5 μg). At five time points (1 h, 4 h, 24 h, 7d, 28d) post-exposure, a complete balance of the [48V]TiO2-NP fate was quantified in organs, tissues, carcass, lavage and body fluids, including excretions. After fast mucociliary airway clearance (fractional range 0.16–0.31), long-term macrophage-mediated clearance (LT-MC) from the alveolar region is 2.6-fold higher after 28d (integral fraction 0.40 ± 0.04) than translocation across the air-blood-barrier (integral fraction 0.15 ± 0.01). A high NP fraction remains in the alveoli (0.44 ± 0.05 after 28d), half of these on the alveolar epithelium and half in interstitial spaces. There is clearance from both retention sites at fractional rates (0.02–0.03 d− 1) by LT-MC. Prior to LT-MC, [48V]TiO2-NP are re-entrained to the epithelium as reported earlier for 20 nm inhaled gold-NP (AuNP) and iridium-NP (IrNP). Comparing the 28-day biokinetics patterns of three different inhaled NP materials TiO2-NP, AuNP and IrNP, the long-term kinetics of interstitial relocation and subsequent re-entrainment onto the lung-epithelium is similar for AuNP and Ir-NP but slower than for TiO2-NP. We discuss mechanisms and pathways of NP relocation and re-entrainment versus translocation. Additionally, after 28 days the integral translocated fractions of TiO2-NP and IrNP across the air-blood-barrier (ABB) are similar and become 0.15 while the translocated AuNP fraction is only 0.04. While NP dissolution proved negligible, translocated TiO2-NP and IrNP are predominantly excreted in urine (~ 0.1) while the urinary AuNP excretion amounts to a fraction of only 0.01. Urinary AuNP excretion is below 0.0001 during the first week but rises tenfold thereafter suggesting delayed disagglomeration. Of note, all three NP dissolve minimally, since no ionic radio-label release was detectable. These biokinetics data of inhaled, same-sized NP suggest significant time-dependent differences of the ABB translocation and subsequent fate in the organism.

中文翻译：

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吸入两小时后，在健康成年大鼠中28天新鲜生成的原始20 nm二氧化钛纳米微粒气溶胶的定量生物动力学

工业生产的TiO2纳米颗粒的数量正在稳步增加，这导致专业人员和消费者吸入吸入的风险增加。吸入颗粒会导致炎症和过敏反应，并且人们担心急性或慢性低剂量暴露还会对健康产生其他负面影响。为研究吸入的TiO2-NP的命运，成年大鼠在气管内吸入48V放射性标记的20 nm TiO2-NP气雾剂（沉积的NP质量1.4±0.5μg）暴露2小时。暴露后五个时间点（1小时，4小时，24小时，7天，28天），在器官，组织，尸体，灌洗液和体液（包括排泄物）中，[48V] TiO2-NP的命运完全平衡。 。经过快速的粘膜纤毛气道清除（分数范围0.16-0.31）后，肺泡区域的长期巨噬细胞介导清除（LT-MC）在28天后（整体分数0.40±0.04）比通过气血屏障的转运（整体分数0.15±0.01）高2.6倍。高的NP分数留在肺泡中（28天后为0.44±0.05），其中一半留在肺泡上皮中，另一半留在间隙中。LT-MC可以从两个保留位点以分数速率（0.02–0.03 d-1）清除。在LT-MC之前，如先前报道的20 nm吸入金NP（AuNP）和铱NP（IrNP）所报道的，[48V] TiO2-NP被重新夹带上皮。比较三种不同的吸入性NP材料TiO2-NP，AuNP和IrNP的28天生物动力学模式，AuNP和Ir-NP的间质迁移和随后重新夹带到肺上皮的长期动力学相似，但比用于TiO2-NP。我们讨论了NP迁移和重新夹带与易位的机制和途径。另外，经过28天后，TiO2-NP和IrNP的整体易位分数跨过气血屏障（ABB）相似并变为0.15，而易位AuNP分数仅为0.04。尽管NP的溶解度可以忽略不计，但易位的TiO2-NP和IrNP主要在尿液中排泄（〜0.1），而尿中AuNP的排泄量仅为0.01。第一周尿AuNP排泄量低于0.0001，但此后升高十倍，表明延迟了团聚。值得注意的是，由于没有离子放射性标记的释放被检测到，所有三个NP的溶解都最小。吸入相同大小NP的这些生物动力学数据表明，生物体内ABB易位和随后的命运存在显着的时间依赖性差异。