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

The biokinetics of a size-selected fraction (70nm median size) of commercially available and V-48-radiolabeled [V-48]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 [V-48]TiO2-nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [V-48]TiO2-nanoparticle doses in the range of 40-240 mu g.kg(-1) bodyweight and making use of the high sensitivity of the radiotracer technique. The [V-48]TiO2-nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for V-48-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 [V-48]TiO2-nanoparticles present in liver and kidneys remained constant (0.03%). [V-48]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 [V-48]TiO2-nanoparticles. This contribution may account for 1/5 of the nanoparticle retention in some organs. After normalizing the fractions of retained [V-48]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.