Quantitative biokinetics of titanium dioxide nanoparticles after intratracheal instillation in rats: Part 3

• Published in: Nanotoxicology Vol. 11; no. 4; pp. 454 - 464
• Main Authors: Kreyling, Wolfgang G., Holzwarth, Uwe, Haberl, Nadine, Kozempel, Ján, Wenk, Alexander, Hirn, Stephanie, Schleh, Carsten, Schäffler, Martin, Lipka, Jens, Semmler-Behnke, Manuela, Gibson, Neil
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.05.2017; Taylor & Francis Ltd
• Subjects: Accumulation; accumulation in secondary organs and tissues; Animals; Blood; Blood-Air Barrier - metabolism; Circulation; different biokinetics patterns after intratracheal instillation and gavage versus intravenous injection; Digestive tract; Dioxides; Dose-Response Relationship, Drug; Environmental Pollutants - administration & dosage; Environmental Pollutants - blood; Environmental Pollutants - pharmacokinetics; Environmental Pollutants - urine; Epithelium; Female; gut-absorption of swallowed nanoparticles; Health risks; Inhalation; Inhalation Exposure; Injection; intratracheal instillation; Intravenous administration; Ions; Kidneys; Larynx; Liver; Lungs; Metabolic Clearance Rate; nanoparticle translocation across the air-blood-barrier; Nanoparticles; Nanoparticles - administration & dosage; Normalizing; Organ Specificity; Organs; Particulates; Radioisotopes; Rats; Rats, Inbred WKY; Respiration; Retention; Retention time; Sensitivity; Size-selected, radiolabeled titanium dioxide nanoparticles; Time Factors; Tissue Distribution; Tissues; Titanium - administration & dosage; Titanium - blood; Titanium - pharmacokinetics; Titanium - urine; Titanium dioxide; Trachea; Vanadium; gut-absorption of swallowed nanoparticles; nanoparticle translocation across the air-blood-barrier; intratracheal instillation; Size-selected, radiolabeled titanium dioxide nanoparticles; accumulation in secondary organs and tissues; different biokinetics patterns after intratracheal instillation and gavage versus intravenous injection
• ISSN: 1743-5390; 1743-5404
• DOI: 10.1080/17435390.2017.1306894

The biokinetics of a size-selected fraction (70 nm median size) of commercially available and 48 V-radiolabeled [ 48 V]TiO 2 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 [ 48 V]TiO 2 -nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [ 48 V]TiO 2 -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]TiO 2 -nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for 48 V-ions not bound to TiO 2 -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 [ 48 V]TiO 2 -nanoparticles present in liver and kidneys remained constant (0.03%). [ 48 V]TiO 2 -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 [ 48 V]TiO 2 -nanoparticles. This contribution may account for 1/5 of the nanoparticle retention in some organs. After normalizing the fractions of retained [ 48 V]TiO 2 -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 2 -particles (including nanoparticles) and accumulation in secondary organs may pose long-term health risks, this issue should be scrutinized more comprehensively.