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

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 48V-radiolabeled [48V]TiO2 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 [48V]TiO2-nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [48V]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 [48V]TiO2-nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for 48V-ions not bound to TiO2-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 [48V]TiO2-nanoparticles present in liver and kidneys remained constant (0.03%). [48V]TiO2-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 [48V]TiO2-nanoparticles. This contribution may account for 1/5 of the nanoparticle retention in some organs. After normalizing the fractions of retained [48V]TiO2-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 TiO2-particles (including nanoparticles) and accumulation in secondary organs may pose long-term health risks, this issue should be scrutinized more comprehensively.

Keywords: Size-selected, radiolabeled titanium dioxide nanoparticles; 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.

MeSH terms

  • Animals
  • Blood-Air Barrier / metabolism*
  • Dose-Response Relationship, Drug
  • Environmental Pollutants / administration & dosage
  • Environmental Pollutants / blood
  • Environmental Pollutants / pharmacokinetics*
  • Environmental Pollutants / urine
  • Female
  • Inhalation Exposure
  • Metabolic Clearance Rate
  • Nanoparticles* / administration & dosage
  • Organ Specificity
  • Radioisotopes
  • Rats
  • Rats, Inbred WKY
  • Time Factors
  • Tissue Distribution
  • Titanium / administration & dosage
  • Titanium / blood
  • Titanium / pharmacokinetics*
  • Titanium / urine
  • Vanadium


  • Environmental Pollutants
  • Radioisotopes
  • Vanadium
  • titanium dioxide
  • Titanium