a Helmholtz Zentrum München - 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):443-453. doi: 10.1080/17435390.2017.1306893. 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 female Wistar-Kyoto rats at retention timepoints 1 h, 4 h, 24 h and 7 days after oral application of a single dose of an aqueous [V]TiO-nanoparticle suspension by intra-esophageal instillation. A completely balanced quantitative body clearance and biokinetics in all organs and tissues was obtained by applying typical [V]TiO-nanoparticle doses in the range of 30-80 μg•kg bodyweight, making use of the high sensitivity of the radiotracer technique. The [V]TiO-nanoparticle content was corrected for nanoparticles in the residual blood retained in organs and tissue after exsanguination and for V-ions not bound to TiO-nanoparticles. Beyond predominant fecal excretion about 0.6% of the administered dose passed the gastro-intestinal-barrier after one hour and about 0.05% were still distributed in the body after 7 days, with quantifiable [V]TiO-nanoparticle organ concentrations present in liver (0.09 ng•g), lungs (0.10 ng•g), kidneys (0.29 ng•g), brain (0.36 ng•g), spleen (0.45 ng•g), uterus (0.55 ng•g) and skeleton (0.98 ng•g). Since chronic, oral uptake of TiO particles (including a nano-fraction) by consumers has continuously increased in the past decades, the possibility of chronic accumulation of such biopersistent nanoparticles in secondary organs and the skeleton raises questions about the responsiveness of their defense capacities, and whether these could be leading to adverse health effects in the population at large. After normalizing the fractions of retained [V]TiO-nanoparticles to the fraction that passed the gastro-intestinal-barrier and reached systemic circulation, the biokinetics was compared to the biokinetics determined after IV-injection (Part 1). Since the biokinetics patterns differ largely, IV-injection is not an adequate surrogate for assessing the biokinetics after oral exposure to TiO nanoparticles.
已研究了经商业途径获得的、经 V 放射性标记的 [V]TiO 纳米颗粒的经尺寸筛选的级分（中值尺寸为 70nm）在雌性 Wistar-Kyoto 大鼠中的生物动力学。在通过食管内滴注给予单次口服[V]TiO 纳米颗粒混悬剂后，于 1h、4h、24h 和 7d 时，通过测定所有器官和组织中放射性示踪剂的保留量来研究其生物动力学。通过应用 30-80μg•kg 体重范围内的典型[V]TiO 纳米颗粒剂量，并利用放射性示踪剂技术的高灵敏度，实现了所有器官和组织中纳米颗粒的完全平衡定量的体内清除和生物动力学。在通过放血去除器官和组织中残留血液中的纳米颗粒以及未与 TiO 纳米颗粒结合的 V 离子后，对[V]TiO 纳米颗粒的含量进行了校正。1 小时后，约 0.6%的给药剂量通过胃肠道屏障，7 天后仍有 0.05%的剂量分布在体内，肝脏（0.09ng•g）、肺（0.10ng•g）、肾（0.29ng•g）、脑（0.36ng•g）、脾（0.45ng•g）、子宫（0.55ng•g）和骨骼（0.98ng•g）中存在可定量的[V]TiO 纳米颗粒器官浓度。由于过去几十年消费者经口摄入 TiO 颗粒（包括纳米级）的慢性增加，这些生物持久性纳米颗粒在次级器官和骨骼中的慢性蓄积的可能性引起了对其防御能力反应性的质疑，以及这些是否会导致普通人群的健康不良影响。将保留的[V]TiO 纳米颗粒的分数归一化为穿过胃肠道屏障并到达全身循环的分数后，将生物动力学与静脉内注射（第 1 部分）确定的生物动力学进行比较。由于生物动力学模式差异很大，因此静脉内注射不是评估经口暴露于 TiO 纳米颗粒后生物动力学的合适替代方法。
