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

<p>The biokinetics of a size-selected fraction (70 nm median size) of commercially available and <sup>48</sup>V-radiolabeled [<sup>48</sup>V]TiO<sub>2</sub> 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 [<sup>48</sup>V]TiO<sub>2</sub>-nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [<sup>48</sup>V]TiO<sub>2</sub>-nanoparticle doses in the range of 40–240 μg·kg<sup>−1</sup> bodyweight and making use of the high sensitivity of the radiotracer technique. The [<sup>48</sup>V]TiO<sub>2</sub>-nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for <sup>48</sup>V-ions not bound to TiO<sub>2</sub>-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 [<sup>48</sup>V]TiO<sub>2</sub>-nanoparticles present in liver and kidneys remained constant (0.03%). [<sup>48</sup>V]TiO<sub>2</sub>-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 [<sup>48</sup>V]TiO<sub>2</sub>-nanoparticles. This contribution may account for 1/5 of the nanoparticle retention in some organs. After normalizing the fractions of retained [<sup>48</sup>V]TiO<sub>2</sub>-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<sub>2</sub>-particles (including nanoparticles) and accumulation in secondary organs may pose long-term health risks, this issue should be scrutinized more comprehensively.</p>