Quantitative biokinetics of titanium dioxide nanoparticles after oral administration in rats (Part 2)

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 and 7days after oral application of a single dose of an aqueous [48V]TiO2-nanoparticle suspension by intra-esophageal instillation. A completely balanced quantitative body clearance and biokinetics in all organs and tissues was obtained by applying typical [48V]TiO2-nanoparticle doses in the range of 30 – 80 μg•kg-1 bodyweight, making use of the high sensitivity of the radiotracer technique. The [48V]TiO2-nanoparticle content was corrected for nanoparticles in the residual blood retained in organs and tissue after exsanguination and for 48V-ions not bound to TiO2-nanoparticles. Beyond predominant fecal excretion about 0.6% of the administered dose passed the gastro-intestinal barrier after 1h and about 0.05% were still distributed in the body after 7 days, with quantifiable [48V]TiO2-nanoparticle organ concentrations present in liver (0.09ng•g-1), lungs (0.10ng•g-1), kidneys (0.29ng•g-1), brain (0.36ng•g-1), spleen (0.45ng•g-1), uterus (0.55ng•g-1) and skeleton (0.98ng•g-1). Since the chronic, oral uptake of TiO2 particles (including a nano-fraction) by consumers continuously increases since decades, the concomitant chronic accumulation of such biopersistent particles in secondary organs and the skeleton raises questions about adverse health effects in the population at large. After normalizing the fractions of retained [48V]TiO2-nanoparticles to the fraction that passed the gastro-intestinal barrier and reached systemic circulation the biokinetics was compared to the biokinetics determined after intravenous injection (Part 1). The biokinetics patterns are very different. Thus, intravenous injection appears not to be an adequate surrogate for assessing the biokinetics after oral exposure to TiO2 nanoparticles.

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

2017-04-27

TAYLOR & FRANCIS LTD

JRC105652

1743-5390,   

http://dx.doi.org/10.1080/17435390.2017.1306893,    https://publications.jrc.ec.europa.eu/repository/handle/JRC105652,   

10.1080/17435390.2017.1306893,