a Helmholtz Center Munich - German Research Center for Environmental Health, Comprehensive Pneumology Center, Institute of Lung Biology and Disease , Neuherberg/Munich , Germany.
b Helmholtz Center Munich - German Research Center for Environmental Health, Institute of Epidemiology 2 , Neuherberg/Munich , Germany.
Nanotoxicology. 2017 May;11(4):454-464. doi: 10.1080/17435390.2017.1306894. Epub 2017 Apr 3.
The biokinetics of a size-selected fraction (70 nm median size) of commercially available and V-radiolabeled [V]TiO nanoparticles has been investigated in healthy adult female Wistar-Kyoto rats at retention time-points of 1 h, 4 h, 24 h, 7 d and 28 d after intratracheal instillation of a single dose of an aqueous [V]TiO-nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [V]TiO-nanoparticle doses in the range of 40-240 μg·kg bodyweight and making use of the high sensitivity of the radiotracer technique. The [V]TiO-nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for V-ions not bound to TiO-nanoparticles. About 4% of the initial peripheral lung dose passed through the air-blood-barrier after 1 h and were retained mainly in the carcass (4%); 0.3% after 28 d. Highest organ fractions of [V]TiO-nanoparticles present in liver and kidneys remained constant (0.03%). [V]TiO-nanoparticles which entered across the gut epithelium following fast and long-term clearance from the lungs via larynx increased from 5 to 20% of all translocated/absorbed [V]TiO-nanoparticles. This contribution may account for 1/5 of the nanoparticle retention in some organs. After normalizing the fractions of retained [V]TiO-nanoparticles to the fraction that reached systemic circulation, the biodistribution was compared with the biodistributions determined after IV-injection (Part 1) and gavage (GAV) (Part 2). The biokinetics patterns after IT-instillation and GAV were similar but both were distinctly different from the pattern after intravenous injection disproving the latter to be a suitable surrogate of the former applications. Considering that chronic occupational inhalation of relatively biopersistent TiO-particles (including nanoparticles) and accumulation in secondary organs may pose long-term health risks, this issue should be scrutinized more comprehensively.
已在健康成年雌性 Wistar-Kyoto 大鼠中研究了商业可得的且 V 放射性标记的 [V]TiO 纳米颗粒的经尺寸选择的级分（70nm 中位数大小）的生物动力学，其在气管内滴注单次剂量的水性 [V]TiO 纳米颗粒混悬液后 1h、4h、24h、7d 和 28d 的保留时间点进行。通过应用典型的 [V]TiO 纳米颗粒剂量（范围 40-240μg·kg 体重）并利用放射性示踪技术的高灵敏度，获得了所有器官和组织中完全平衡的定量生物分布。[V]TiO 纳米颗粒的含量经过校正，以校正器官和组织中残留的血液和未与 TiO 纳米颗粒结合的 V 离子。在 1h 后，约有 4%的初始肺内剂量穿过气-血屏障，并主要保留在尸体内（4%）；28d 后为 0.3%。存在于肝脏和肾脏中的 [V]TiO 纳米颗粒的最高器官分数保持不变（0.03%）。通过快速和长期从肺部通过喉清除而穿过肠上皮进入的 [V]TiO 纳米颗粒从所有转运/吸收的 [V]TiO 纳米颗粒的 5%增加到 20%。这一贡献可能占某些器官中纳米颗粒保留量的 1/5。将保留的 [V]TiO 纳米颗粒的分数归一化为到达全身循环的分数后，将其与静脉内注射（第 1 部分）和灌胃（GAV）（第 2 部分）确定的生物分布进行比较。气管内滴注和灌胃后的生物动力学模式相似，但均与静脉内注射后的模式明显不同，证明后者不是前者应用的合适替代物。考虑到相对生物持久性的 TiO 颗粒（包括纳米颗粒）的慢性职业性吸入和在次级器官中的积累可能会带来长期健康风险，因此应该更全面地审查这一问题。
