Title: Quantitative biokinetics over a 28 day period of freshly generated, pristine, 20 nm titanium dioxide nanoparticle aerosols in healthy adult rats after a single two-hour inhalation exposure
Authors: KREYLING WOLFGANGHOLZWARTH UWESCHLEH CARSTENHIRN STEPHANIEWENK A.SCHAFFLER M.HABERL NADINESEMMLER-BEHNKE MANUELAGIBSON PETER
Citation: PARTICLE AND FIBRE TOXICOLOGY vol. 16 no. 29 p. 1-27
Publisher: BIOMED CENTRAL LTD
Publication Year: 2019
JRC N°: JRC115423
ISSN: 1743-8977 (online)
URI: https://publications.jrc.ec.europa.eu/repository/handle/JRC115423
DOI: 10.1186/s12989-019-0303-7
Type: Articles in periodicals and books
Abstract: Background Industrially produced quantities of TiO2 nanoparticles are steadily rising, leading to an increasing risk of inhalation exposure for both professionals and consumers. Particle inhalation can result in inflammatory and allergic responses, and there are concerns about other negative health effects from either acute or chronic low-dose exposure. Results To study the fate of inhaled TiO2-NP, adult rats were exposed to 2-hour intra-tracheal inhalations of 48V-radiolabeled, 20nm TiO2-NP aerosols (deposited NP-mass 1.4±0.5 μg). At five time points (1h, 4h, 24h, 7d, 28d) post-exposure, a complete balance of the [48V]TiO2-NP fate was obtained by quantifying the [48V]TiO2-NP in selected organs, tissues, carcass, lavage and body fluids, including excretions. After fast mucociliary airway clearance (fractional range 0.16-0.31), long-term macrophage-mediated clearance (LT-MC) from the alveolar region is twice as high after 28d (integral fraction 0.31±0.04) as translocation across the air-blood-barrier (integral fraction 0.15±0.01). There was no detectable lymph-node clearance. A high NP fraction remains in the alveoli (0.44±0.05 after 28d), half of these on the alveolar epithelium and half in interstitial spaces. There is clearance from both retention sites at fractional rates (0.02-0.03 d-1) by LT-MC. Prior to LT-MC, [48V]TiO2-NP are reentrained to the epithelium as reported earlier for 20nm inhaled gold-NP (AuNP) and iridium-NP (IrNP). Conclusion Comparing the 28-day biokinetics patterns of three different inhaled NP materials TiO2-NP, AuNP and IrNP, the long-term kinetics of interstitial relocation and subsequent reentrainment onto the lung-epithelium is similar for AuNP and Ir-NP but slower than for TiO2-NP. Additionally, after 28 days the integral translocated fractions of TiO2-NP and IrNP across the air-blood-barrier (ABB) are similar and become 0.15 while the translocated AuNP fraction is only 0.04. Translocated TiO2-NP and IrNP are predominantly excreted in urine (~0.1) while the urinary AuNP excretion amounts to a fraction of only 0.01. Urinary AuNP excretion is below 0.0001 during the first week but rises tenfold thereafter suggesting delayed disagglomeration. Of note, all three NP dissolve minimally, since no ionic radio-label release was detectable. These biokinetics data of inhaled, same-sized NP suggest significant time-dependent differences of the ABB translocation and subsequent fate in the organism.
JRC Directorate:Health, Consumers and Reference Materials

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