Quantitative biokinetics of titanium dioxide nanoparticles after oral application in rats: Part 2

• Published in: Nanotoxicology Vol. 11; no. 4; pp. 443 - 453
• Main Authors: Kreyling, Wolfgang G., Holzwarth, Uwe, Schleh, Carsten, Kozempel, Ján, Wenk, Alexander, Haberl, Nadine, Hirn, Stephanie, Schäffler, Martin, Lipka, Jens, Semmler-Behnke, Manuela, Gibson, Neil
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.05.2017; Taylor & Francis Ltd
• Subjects: Accumulation; accumulation in secondary organs and tissues; Administration, Oral; Animals; Blood; Brain; Circulation; Consumers; different biokinetics pattern after gavage versus intravenous injection; Dioxides; Dose-Response Relationship, Drug; Environmental Pollutants - administration & dosage; Environmental Pollutants - blood; Environmental Pollutants - pharmacokinetics; Environmental Pollutants - urine; Esophagus; Excretion; Exposure; Feces - chemistry; Female; Gastrointestinal Tract - metabolism; gavage; gut-absorption; Health; Injection; Intestine; Ions; Kidneys; Liver; Lungs; Metabolic Clearance Rate; Nanoparticles; Nanoparticles - administration & dosage; Normalizing; Oral cavity; Organs; Particle Size; Particulates; Radioisotopes; Rats; Rats, Inbred WKY; Retention; Sensitivity; Size-selected, radiolabeled titanium dioxide nanoparticles; Spleen; Surface Properties; Time Factors; Tissue Distribution; Tissues; Titanium - administration & dosage; Titanium - blood; Titanium - pharmacokinetics; Titanium - urine; Titanium dioxide; Uterus; Vanadium; gavage; Size-selected, radiolabeled titanium dioxide nanoparticles; different biokinetics pattern after gavage versus intravenous injection; gut-absorption; accumulation in secondary organs and tissues
• ISSN: 1743-5390; 1743-5404
• DOI: 10.1080/17435390.2017.1306893

The biokinetics of a size-selected fraction (70 nm median size) of commercially available and 48 V-radiolabeled [ 48 V]TiO 2 nanoparticles has been investigated in female Wistar-Kyoto rats at retention timepoints 1 h, 4 h, 24 h and 7 days after oral application of a single dose of an aqueous [ 48 V]TiO 2 -nanoparticle suspension by intra-esophageal instillation. A completely balanced quantitative body clearance and biokinetics in all organs and tissues was obtained by applying typical [ 48 V]TiO 2 -nanoparticle doses in the range of 30-80 μg*kg −1 bodyweight, making use of the high sensitivity of the radiotracer technique. The [ 48 V]TiO 2 -nanoparticle content was corrected for nanoparticles in the residual blood retained in organs and tissue after exsanguination and for 48 V-ions not bound to TiO 2 -nanoparticles. Beyond predominant fecal excretion about 0.6% of the administered dose passed the gastro-intestinal-barrier after one hour and about 0.05% were still distributed in the body after 7 days, with quantifiable [ 48 V]TiO 2 -nanoparticle organ concentrations present in liver (0.09 ng*g −1 ), lungs (0.10 ng*g −1 ), kidneys (0.29 ng*g −1 ), brain (0.36 ng*g −1 ), spleen (0.45 ng*g −1 ), uterus (0.55 ng*g −1 ) and skeleton (0.98 ng*g −1 ). Since chronic, oral uptake of TiO 2 particles (including a nano-fraction) by consumers has continuously increased in the past decades, the possibility of chronic accumulation of such biopersistent nanoparticles in secondary organs and the skeleton raises questions about the responsiveness of their defense capacities, and whether these could be leading to adverse health effects in the population at large. After normalizing the fractions of retained [ 48 V]TiO 2 -nanoparticles to the fraction that passed the gastro-intestinal-barrier and reached systemic circulation, the biokinetics was compared to the biokinetics determined after IV-injection (Part 1). Since the biokinetics patterns differ largely, IV-injection is not an adequate surrogate for assessing the biokinetics after oral exposure to TiO 2 nanoparticles.