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

Abstract

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

Biodistribution, Clearance, and Long‐Term Fate of Clinically Relevant Nanomaterials

“…The biokinetics and biodistribution of nanomaterials following intravenous exposure is different from the biokinetics/biodistribution of nanomaterials administered to the respiratory tract as described earlier . In addition, a very recent series of three publications by Kreyling et al showed that the biokinetics of intravenously injected nanomaterials does not represent a surrogate biokinetic approach for pulmonary or oral routes of exposure . The authors employed 70 nm radiolabeled TiO 2 NPs containing 48 V in rats to study the biokinetics and biodistribution in various tissues over the period of 1 h to 28 d. After intravenous injection, the highest titanium accumulation was found in the liver, followed by the spleen, carcass, skeleton, and blood after 1 h, after which the blood content decreased rapidly, while the distribution in the other organs and tissues remained constant until day 28.…”

Does intranasal instillation TiO2 cause pulmonary tumorigenesis in male mice?

“…Even so, the accumulated TiO 2 dose in the lungs of mice is peculiarly extremely small, only few nanograms. This is many orders less than what has been reported in the literature (even if the reported doses were the accumulated ones) …”

Occupational exposure to inhaled nanoparticles: Are young workers being left in the dust?

“…For more than a decade, epidemiological studies have demonstrated an association between exposure to increased concentrations of fine and UFPs and adverse health effects, namely pulmonary and cardiovascular morbidity . Particles in the nano‐range are of particular concern as they may translocate and be transported by mechanisms such as macrophage‐mediated clearance, interstitial‐lymphatic clearance and the blood circulation to distant sites and organs . Recently, the increase in the production and application of engineered nanomaterials (ENMs) has raised concern about occupational exposures and resulting health effects.…”