title: Pulmonary effects of inhalation of spark-generated silver nanoparticles in Brown-Norway and Sprague-Dawley rats.
abstract: The increasing use of silver nanoparticles (AgNPs) in consumer products is concerning. We examined the potential toxic effects when inhaled in Brown-Norway (BN) rats with a pre-inflammatory state compared to Sprague-Dawley (SD) rats.
  
  
  
  We determined the effect of AgNPs generated from a spark generator (mass concentration: 600-800 μg/mm(3); mean diameter: 13-16 nm; total lung doses: 8 [Low] and 26-28 [High] μg) inhaled by the nasal route in both rat strains. Rats were sacrificed at day 1 and day 7 after exposure and measurement of lung function.
  
  
  
  In both strains, there was an increase in neutrophils in bronchoalveolar lavage (BAL) fluid at 24 h at the high dose, with concomitant eosinophilia in BN rats. While BAL inflammatory cells were mostly normalised by Day 7, lung inflammation scores remained increased although not the tissue eosinophil scores. Total protein levels were elevated at both lung doses in both strains. There was an increase in BAL IL-1β, KC, IL-17, CCL2 and CCL3 levels in both strains at Day 1, mostly at high dose. Phospholipid levels were increased at the high dose in SD rats at Day 1 and 7, while in BN rats, this was only seen at Day 1; surfactant protein D levels decreased at day 7 at the high dose in SD rats, but was increased at Day 1 at the low dose in BN rats. There was a transient increase in central airway resistance and in tissue elastance in BN rats at Day 1 but not in SD rats. Positive silver-staining was seen particularly in lung tissue macrophages in a dose and time-dependent response in both strains, maximal by day 7. Lung silver levels were relatively higher in BN rat and present at day 7 in both strains.
  
  
  
  Presence of cellular inflammation and increasing silver-positive macrophages in lungs at day 7, associated with significant levels of lung silver indicate that lung toxicity is persistent even with the absence of airway luminal inflammation at that time-point. The higher levels and persistence of lung silver in BN rats may be due to the pre-existing inflammatory state of the lungs.
authors.affiliation: Airways Disease, National Heart & Lung Institute, Imperial College London, Dovehouse St, London, SW3 6LY, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Seiffert
authors.affiliation: Nanoparticle Inhalation Research Group, Public Health England, Oxfordshire, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Buckley
authors.affiliation: Department of Material Science, Chemistry and the London Centre for Nanotechnology, Imperial College, London, SW3, UK.
authors.forename: Bey
authors.initials: B
authors.lastname: Leo
authors.affiliation: Department of Clinical Biochemistry, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, W6 8RF, UK.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: Airways Disease, National Heart & Lung Institute, Imperial College London, Dovehouse St, London, SW3 6LY, UK.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Airways Disease, National Heart & Lung Institute, Imperial College London, Dovehouse St, London, SW3 6LY, UK.
authors.forename: Ranran
authors.initials: R
authors.lastname: Dai
authors.affiliation: Airways Disease, National Heart & Lung Institute, Imperial College London, Dovehouse St, London, SW3 6LY, UK.
authors.forename: Farhana
authors.initials: F
authors.lastname: Hussain
authors.affiliation: Nanoparticle Inhalation Research Group, Public Health England, Oxfordshire, UK.
authors.forename: Chang
authors.initials: C
authors.lastname: Guo
authors.affiliation: Nanoparticle Inhalation Research Group, Public Health England, Oxfordshire, UK.
authors.forename: James
authors.initials: J
authors.lastname: Warren
authors.affiliation: Nanoparticle Inhalation Research Group, Public Health England, Oxfordshire, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Hodgson
authors.affiliation: Nicholas School of Environment & Duke Global Health Institute, Duke University, Durham, USA.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Material Science, Chemistry and the London Centre for Nanotechnology, Imperial College, London, SW3, UK.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Ryan
authors.affiliation: Nicholas School of Environment & Duke Global Health Institute, Duke University, Durham, USA.
authors.forename: Junfeng Jim
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Department of Material Science, Chemistry and the London Centre for Nanotechnology, Imperial College, London, SW3, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Porter
authors.affiliation: Airways Disease, National Heart & Lung Institute, Imperial College London, Dovehouse St, London, SW3 6LY, UK.
authors.forename: Terry D
authors.initials: TD
authors.lastname: Tetley
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gow
authors.affiliation: Nanoparticle Inhalation Research Group, Public Health England, Oxfordshire, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Smith
authors.affiliation: Airways Disease, National Heart & Lung Institute, Imperial College London, Dovehouse St, London, SW3 6LY, UK. f.chung@imperial.ac.uk.
authors.forename: Kian Fan
authors.identifier: 0000-0001-7101-1426
authors.initials: KF
authors.lastname: Chung
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D010743:Phospholipids / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects; D012834:Silver / Q000633:toxicity*; D013997:Time Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D010743:Phospholipids; D037663:Pulmonary Surfactant-Associated Protein D; D012834:Silver
keywords: Inflammation; Inhalation; Lungs; Silver nanospheres