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|Title:||Age-dependent rat lung deposition patterns of inhaled 20 nanometer gold nanoparticles and their quantitative biokinetics in adult rats.|
|Authors:||KREYLING WOLFGANG; MÖLLER WINFRIED; HOLZWARTH UWE; HIRN S.; WENK A.; SCHLEH C.; SCHAFFLER M.; HABERL NADINE; GIBSON PETER; SCHITTNY JOHANNES|
|Citation:||ACS NANO vol. 12 no. 8 p. 7771-7790|
|Publisher:||AMER CHEMICAL SOC|
|Type:||Articles in periodicals and books|
|Abstract:||The increasing use of gold nanoparticles leads to a possible increase of exposure by inhalation. Therefore, we have studied the deposition patterns of inhaled 20 nm gold nanoparticles (AuNP) in 7−90 day old rats and their biokinetics in 60 day old ones. Wistar−Kyoto rats inhaled intratracheally 20 nm 195Au-radiolabeled AuNP by negative pressure ventilation over 2 h. Immediately afterward lungs were excised, inflated and microwave dried. AuNP deposition was analyzed by single-photon emission computed tomography, computed-tomography and autoradiography. Completely balanced, quantitative biodistributions in major organs and all body tissues and total excretion were analyzed from 1 h to 28 d after inhalation. Intratracheal inhalation caused AuNP deposition predominately in the caudal lungs, independent of age. About 30% AuNP were deposited on airway epithelia and rapidly cleared by mucociliary clearance. About 80% of AuNP deposited in alveoli was relocated from the epithelium into the interstitium within 24 h and was inaccessible to broncho-alveolar lavage. During interstitial long-term retention, re-entrainment within macrophages back onto the lung epithelium and to the larynx and gastrointestinal tract (GIT) dominated AuNP clearance (rate 0.03 d−1) In contrast, AuNP-translocation across the air−blood barrier was much smaller leading to persistent retention in secondary organs and tissues in the ranking order liver > soft issue > spleen > kidneys > skeleton > blood > uterus > heart > brain. The age-independent, inhomogeneous AuNP deposition was probably caused by the negative pressure ventilation. Long-term AuNP clearance was dominated by macrophage-mediated transport from the interstitium to the larynx and GIT. Translocation across the rat air−blood barrier appeared to be similar to that of humans for similar sized AuNP.|
|JRC Directorate:||Health, Consumers and Reference Materials|
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