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 48V-radiolabeled [48V]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 [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 1h and were retained mainly in the carcass (4%); 0.3% after 28d. 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 5-20% 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 (Part-2). The biokinetics patterns after IT instillation and gavage 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 chronic occupational inhalation of minimally dissolving TiO2-particles (including nanoparticles) and accumulation in secondary organs may pose long-term health risks to be scrutinized more comprehensively.

KREYLING Wolfgang;  HOLZWARTH Uwe;  HIRN Stephanie;  KOZEMPEL J.;  WENK A.;  HABERL Nadine;  SCHLEH Carsten;  SCHAEFFLER Martin;  LIPKA Jens;  SEMMLER-BEHNKE Manuela;  GIBSON Peter; 

2017-04-27

TAYLOR & FRANCIS LTD

JRC105653

1743-5390,   

http://dx.doi.org/10.1080/17435390.2017.1306894,    https://publications.jrc.ec.europa.eu/repository/handle/JRC105653,   

10.1080/17435390.2017.1306894,