title: Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure.
abstract: Increased use of nanomaterials has raised concerns about the potential for undesirable human health and environmental effects. Releases into the air may occur and, therefore, the inhalation route is of specific interest. Here we tested copper oxide nanoparticles (CuO NPs) after repeated inhalation as hazard data for this material and exposure route is currently lacking for risk assessment.
  
  
  
  Rats were exposed nose-only to a single exposure concentration and by varying the exposure time, different dose levels were obtained (C × T protocol). The dose is expressed as 6 h-concentration equivalents of 0, 0.6, 2.4, 3.3, 6.3, and 13.2 mg/m(3) CuO NPs, with a primary particle size of 10 9.2-14 nm and an MMAD of 1.5 μm.
  
  
  
  Twenty-four hours after a 5-d exposure, dose-dependent lung inflammation and cytotoxicity were observed. Histopathological examinations indicated alveolitis, bronchiolitis, vacuolation of the respiratory epithelium, and emphysema in the lung starting at 2.4 mg/m(3). After a recovery period of 22 d, limited inflammation was still observed, but only at the highest dose of 13.2 mg/m(3). The olfactory epithelium in the nose degenerated 24 h after exposure to 6.3 and 13.2 mg/m(3), but this was restored after 22 d. No histopathological changes were detected in the brain, olfactory bulb, spleen, kidney and liver.
  
  
  
  A 5-d, 6-h/day exposure equivalent to an aerosol of agglomerated CuO NPs resulted in a dose-dependent toxicity in rats, which almost completely resolved during a 3-week post-exposure period.
authors.affiliation: a National Institute for Public Health and the Environment , Bilthoven , The Netherlands .
authors.forename: Ilse
authors.initials: I
authors.lastname: Gosens
authors.affiliation: a National Institute for Public Health and the Environment , Bilthoven , The Netherlands .|b Institute for Risk Assessment Studies, Utrecht University , Utrecht , The Netherlands .
authors.forename: Flemming R
authors.initials: FR
authors.lastname: Cassee
authors.affiliation: c ECSIN-European Center for the Sustainable Impact of Nanotechnology, Veneto Nanotech S.C.P.A. , Rovigo , Italy .
authors.forename: Michela
authors.initials: M
authors.lastname: Zanella
authors.affiliation: c ECSIN-European Center for the Sustainable Impact of Nanotechnology, Veneto Nanotech S.C.P.A. , Rovigo , Italy .
authors.forename: Laura
authors.initials: L
authors.lastname: Manodori
authors.affiliation: d Informatics and Statistics, University Ca' Foscari of Venice, INCA - VEGAPARK , Venice , Italy .
authors.forename: Andrea
authors.initials: A
authors.lastname: Brunelli
authors.affiliation: e National Research Council - Institute of Science and Technology for Ceramics , Faenza , Italy , and.
authors.forename: Anna Luisa
authors.initials: AL
authors.lastname: Costa
authors.affiliation: a National Institute for Public Health and the Environment , Bilthoven , The Netherlands .
authors.forename: Bas G H
authors.initials: BG
authors.lastname: Bokkers
authors.affiliation: a National Institute for Public Health and the Environment , Bilthoven , The Netherlands .
authors.forename: Wim H
authors.initials: WH
authors.lastname: de Jong
authors.affiliation: f School of Life Sciences, Heriot-Watt University, Nanosafety Research Group , Edinburgh , UK.
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.affiliation: d Informatics and Statistics, University Ca' Foscari of Venice, INCA - VEGAPARK , Venice , Italy .
authors.forename: Danail
authors.initials: D
authors.lastname: Hristozov
authors.affiliation: f School of Life Sciences, Heriot-Watt University, Nanosafety Research Group , Edinburgh , UK.
authors.forename: Vicki
authors.initials: V
authors.lastname: Stone
mesh_terms: D000336:Aerosols; D000818:Animals; D001822:Body Burden; D003300:Copper / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects* / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013499:Surface Properties
chemical_list: D000336:Aerosols; D003300:Copper; C030973:cupric oxide
keywords: Benchmark dose modelling; copper oxide; nanoparticles; organ burden; pulmonary toxicity