Particle size dependent deposition and pulmonary inflammation after short-term inhalation of silver nanoparticles

Hedwig M. Braakhuis*, Ilse Gosens, Petra Krystek, John A. F. Boere, Flemming R. Cassee, Paul H. B. Fokkens, Jan Andries Post, Henk van Loveren, Margriet V. D. Z. Park

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Although silver nanoparticles are currently used in more than 400 consumer products, it is not clear to what extent they induce adverse effects after inhalation during production and use. In this study, we determined the lung burden, tissue distribution, and the induction and recovery of adverse effects after short-term inhalation exposure to 15 nm and 410 nm silver nanoparticles. Methods: Rats were nose-only exposed to clean air, 15 nm silver nanoparticles (179 mu g/m(3)) or 410 nm silver particles (167 mu g/m(3)) 6 hours per day, for four consecutive days. Tissue distribution and the induction of pulmonary toxicity were determined at 24 hours and 7 days after exposure and compared with the internal alveolar dose. Presence of silver nanoparticles in lung cells was visualized by transmission electron microscopy (TEM). Results: Exposure to 15 nm silver nanoparticles induced moderate pulmonary toxicity compared to the controls, indicated by a 175-fold increased influx of neutrophils in the lungs, a doubling of cellular damage markers in the lungs, a 5-fold increase in pro-inflammatory cytokines, and a 1.5-fold increase in total glutathione at 24 hours after exposure. All the observed effects disappeared at 7 days after exposure. No effects were observed after exposure to 410 nm silver particles. The internal alveolar mass dose of the 15 nm nanoparticles was 3.5 times higher compared to the 410 nm particles, which equals to a 66,000 times higher particle number. TEM analysis revealed 15 nm nanoparticles in vesicles and nuclei of lung cells, which were decreased in size to
Original languageEnglish
Article number49
JournalParticle and Fibre Toxicology
Publication statusPublished - 17 Sept 2014


  • Nanoparticles
  • Inhalation exposure
  • Pulmonary toxicity
  • Cellular uptake
  • Dissolution


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