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