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Quantitative evaluation of local pulmonary distribution of TiO 2 in rats following single or multiple intratracheal administrations of TiO 2 nanoparticles using X‐ray fluorescence microscopy
Author(s) -
Zhang Guihua,
Shinohara Naohide,
Kano Hirokazu,
Senoh Hideki,
Suzuki Masaaki,
Sasaki Takeshi,
Fukushima Shoji,
Gamo Masashi
Publication year - 2016
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3287
Subject(s) - lung , distribution (mathematics) , intratracheal instillation , chemistry , fluorescence microscope , pulmonary toxicity , nuclear medicine , medicine , pathology , pharmacology , fluorescence , mathematics , physics , bronchoalveolar lavage , mathematical analysis , quantum mechanics
Uneven pulmonary nanoparticle (NP) distribution has been described when using single‐dose intratracheal administration tests. Multiple‐dose intratracheal administrations with small quantities of NPs are expected to improve the unevenness of each dose. The differences in local pulmonary NP distribution (called microdistribution) between single‐ and multiple‐dose administrations may cause differential pulmonary responses; however, this has not been evaluated. Here, we quantitatively evaluated the pulmonary microdistribution (per mesh: 100 μm × 100 μm) of TiO 2 in lung sections from rats following one, two, three, or four doses of TiO 2 NPs at a same total dosage of 10 mg kg −1 using X‐ray fluorescence microscopy. The results indicate that: (i) multiple‐dose administrations show lower variations in TiO 2 content (ng mesh −1 ) for sections of each lobe; (ii) TiO 2 appears to be deposited more in the right caudal and accessory lobes located downstream of the administration direction of NP suspensions, and less so in the right middle lobes, irrespective of the number of doses; (iii) there are not prominent differences in the pattern of pulmonary TiO 2 microdistribution between rats following single and multiple doses of TiO 2 NPs. Additionally, the estimation of pulmonary TiO 2 deposition for multiple‐dose administrations imply that every dose of TiO 2 would be randomly deposited only in part of the fixed 30–50% of lung areas. The evidence suggests that multiple‐dose administrations do not offer remarkable advantages over single‐dose administration on the pulmonary NP microdistribution, although multiple‐dose administrations may reduce variations in the TiO 2 content for each lung lobe. Copyright © 2016 John Wiley & Sons, Ltd.