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Kreyling, W.G. ; Holzwarth, U.* ; Haberl, N. ; Kozempel, J.* ; Wenk, A. ; Hirn, S. ; Schleh, C. ; Schäffler, M. ; Lipka, J. ; Semmler-Behnke, M. ; Gibson, N.*

Quantitative biokinetics of titanium dioxide nanoparticles after intratracheal instillation in rats (Part 3).

Nanotox. 11, 454-464 (2017)
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The biokinetics of a size-selected fraction (70nm median size) of commercially available and (48)V-radiolabeled [(48)V]TiO2 nanoparticles has been investigated in healthy adult female Wistar-Kyoto rats at retention time-points of 1h, 4h, 24h, 7d and 28d after intratracheal instillation of a single dose of an aqueous [(48)V]TiO2-nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [(48)V]TiO2-nanoparticle doses in the range of 40-240 μg·kg(-1) bodyweight and making use of the high sensitivity of the radiotracer technique. The [(48)V]TiO2-nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for (48)V-ions not bound to TiO2-nanoparticles. About 4% of the initial peripheral lung dose passed through the air-blood-barrier after 1h and were retained mainly in the carcass (4%); 0.3% after 28d. Highest organ fractions of [(48)V]TiO2-nanoparticles present in liver and kidneys remained constant (0.03%). [(48)V]TiO2-nanoparticles which entered across the gut epithelium following fast and long-term clearance from the lungs via larynx increased from 5-20% of all translocated/absorbed [(48)V]TiO2-nanoparticles. This contribution may account for 1/5 of the nanoparticle retention in some organs. After normalizing the fractions of retained [(48)V]TiO2-nanoparticles to the fraction that reached systemic circulation, the biodistribution was compared with the biodistributions determined after IV-injection (Part-1) and gavage (Part-2). The biokinetics patterns after IT-instillation and gavage 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 TiO2-particles (including nanoparticles) and accumulation in secondary organs may pose long-term health risks, this issue should be scrutinized more comprehensively.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Size-selected ; Accumulation In Secondary Organs And Tissues ; Different Biokinetics Patterns After Intratracheal Instillation And Gavage Versus Intravenous Injection ; Gut-absorption Of Swallowed Nanoparticles ; Intratracheal Instillation ; Nanoparticle Translocation Across The Air-blood-barrier ; Radiolabeled Titanium Dioxide Nanoparticles; Insoluble Iridium Particles; Gold Nanoparticles; Inhaled Nanoparticles; Lung Clearance; Ultrafine; Translocation; Size; Inhalation; Deposition; Epithelium
ISSN (print) / ISBN 1743-5390
e-ISSN 1743-5404
Zeitschrift Nanotoxicology
Quellenangaben Band: 11, Heft: 4, Seiten: 454-464 Artikelnummer: , Supplement: ,
Verlag Informa Healthcare
Verlagsort London
Begutachtungsstatus Peer reviewed