title: Influence of particle size on persistence and clearance of aerosolized silver nanoparticles in the rat lung.
abstract: The growing use of silver nanoparticles (AgNPs) in consumer products raises concerns about potential health effects. This study investigated the persistence and clearance of 2 different size AgNPs (20 and 110 nm) delivered to rats by single nose-only aerosol exposures (6 h) of 7.2 and 5.4 mg/m(3), respectively. Rat lung tissue was assessed for silver accumulations using inductively-coupled plasma mass spectrometry (ICP-MS), autometallography, and enhanced dark field microscopy. Involvement of tissue macrophages was assessed by scoring of silver staining in bronchoalveolar lavage fluid (BALF). Silver was abundant in most macrophages at 1 day post-exposure. The group exposed to 20 nm AgNP had the greatest number of silver positive BALF macrophages at 56 days post-exposure. While there was a significant decrease in the amount of silver in lung tissue at 56 days post-exposure compared with 1 day following exposure, at least 33% of the initial delivered dose was still present for both AgNPs. Regardless of particle size, silver was predominantly localized within the terminal bronchial/alveolar duct junction region of the lung associated with extracellular matrix and within epithelial cells. Inhalation of both 20 and 110 nm AgNPs resulted in a persistence of silver in the lung at 56 days post-exposure and local deposition as well as accumulation of silver at the terminal bronchiole alveolar duct junction. Further the smaller particles, 20 nm AgNP, produced a greater silver burden in BALF macrophages as well as greater persistence of silver positive macrophages at later timepoints (21 and 56 days).
authors.affiliation: *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817.
authors.forename: Donald S
authors.initials: DS
authors.lastname: Anderson
authors.affiliation: *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817.
authors.forename: Esther S
authors.initials: ES
authors.lastname: Patchin
authors.affiliation: *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817.
authors.forename: Rona M
authors.initials: RM
authors.lastname: Silva
authors.affiliation: *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Uyeminami
authors.affiliation: *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817.
authors.forename: Arjun
authors.initials: A
authors.lastname: Sharmah
authors.affiliation: *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817.
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.affiliation: *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817.
authors.forename: Gautom K
authors.initials: GK
authors.lastname: Das
authors.affiliation: *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Brown
authors.affiliation: *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Shannahan
authors.affiliation: *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817.
authors.forename: Terry
authors.initials: T
authors.lastname: Gordon
authors.affiliation: *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817.
authors.forename: Lung Chi
authors.initials: LC
authors.lastname: Chen
authors.affiliation: *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817 *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817 *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817.
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
authors.affiliation: *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817 *Center for Health and the Environment, Department of Chemistry, Department of Mechanical and Aerospace Engineering, University of California Davis, Davis, California 95616, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, Department of Environmental Medicine, Langone Medical Center, New York University, Tuxedo, New York 10987, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616 and Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, California 95817 lsvanwinkle@ucdavis.edu.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Van Winkle
mesh_terms: D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008264:Macrophages / Q000648:ultrastructure; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012834:Silver / Q000737:chemistry*
chemical_list: D000336:Aerosols; D012834:Silver
keywords: engineered nanomaterials; inhalation; inhaled; lung; macrophage