Age-dependent rat lung deposition patterns of inhaled 20 nanometer gold nanoparticles and their quantitative biokinetics in adult rats.

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.

KREYLING Wolfgang;  MÖLLER Winfried;  HOLZWARTH Uwe;  HIRN S.;  WENK A.;  SCHLEH C.;  SCHAFFLER M.;  HABERL Nadine;  GIBSON Peter;  SCHITTNY Johannes; 

2018-10-12

AMER CHEMICAL SOC

JRC111287

1936-0851,   

https://pubs.acs.org/doi/10.1021/acsnano.8b01826,    https://publications.jrc.ec.europa.eu/repository/handle/JRC111287,   

10.1021/acsnano.8b01826,