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Kreyling, W.G.

Discovery of unique and ENM-specific pathophysiologic pathways: Comparison of the translocation of inhaled iridium nanoparticles from nasal epithelium versus alveolar epithelium towards the brain of rats.

Toxicol. Appl. Pharmacol. 299, 41-46 (2016)
Postprint DOI PMC
Open Access Green
The biokinetics of inhaled nanoparticles (NP) is more complex than that of larger particles since NP may NP deposited on the nasal mucosa of the upper respiratory tract (URT) may translocate to the olfactory bulb of the brain and also via the trigeminus (URT neuronal route); and (b) NP deposited in the lower respiratory tract (LRT) may cross the ABB into blood and enter the brain across the blood-brain-barrier (BBB) or take a neuronal route from enervated tracheo-bronchial epithelia via the vagus nerve. Translocation from both - the URT and the LRT - are quantified during the first 24h after a 1-hour aerosol inhalation of 20nm-sized, (192)Ir radiolabeled iridium NP by healthy adult rats using differential exposures: (I) nose-only exposure of the entire respiratory tract or (II) intratracheal (IT) inhalation of intubated and ventilated rats, thereby bypassing the URT and extrathoracic nasal passages. After nose-only exposure brain accumulation (BrAcc) is significantly nine-fold higher than after IT inhalation since the former results from both pathways (a+b) while the latter exposure comes only from pathway (b). Interestingly, there are significantly more circulating NP in blood 24h after nose-only inhalation than after IT inhalation. Distinguishing translocation from URT versus LRT estimated from the differential inhalation exposures, the former is significantly higher (8-fold) than from the LRT. Although the BrAcc fraction is rather low compared to total NP deposition after this short-term exposure, this study proofs that inhaled insoluble NP can accumulate in the brain from both - URT and LRT which may trigger and/or modulate adverse health effects in the central nervous system (CNS) during chronic exposure.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Brain Accumulation ; Iridium Nanoparticle ; Neuronal Pathway From Upper Respiratory Tract ; Nose-only And Intratracheal Inhalation ; Quantitative Biokinetics ; Systemic Pathway From Lower Respiratory Tract; Ultrafine Particles; Gold Nanoparticles; Lung; Deposition; Biokinetics; Organs; Model; Size
ISSN (print) / ISBN 0041-008X
e-ISSN 1096-0333
Zeitschrift Toxicology and Applied Pharmacology
Quellenangaben Band: 299, Heft: , Seiten: 41-46 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort San Diego
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)