Quantitative biokinetics of titanium dioxide nanoparticles after intratracheal instillation in rats: Part 3 |
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| Authors: | Wolfgang G. Kreyling Uwe Holzwarth Nadine Haberl Ján Kozempel Alexander Wenk Stephanie Hirn |
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| Affiliation: | 1. Helmholtz Center Munich – German Research Center for Environmental Health, Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Neuherberg/Munich, Germany;2. Helmholtz Center Munich – German Research Center for Environmental Health, Institute of Epidemiology 2, Neuherberg/Munich, Germany;3. European Commission, Joint Research Centre, Directorate F – Health, Consumers and Reference Materials, Ispra, Italy |
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| Abstract: | 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. |
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| Keywords: | Size-selected, radiolabeled titanium dioxide nanoparticles intratracheal instillation nanoparticle translocation across the air-blood-barrier gut-absorption of swallowed nanoparticles accumulation in secondary organs and tissues different biokinetics patterns after intratracheal instillation and gavage versus intravenous injection |
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