Airway irritation, inflammation, and toxicity in mice following inhalation of metal oxide nanoparticles

Larsen, Søren T.; Jackson, Petra; Poulsen, Steen S.; Levin, Marcus; Jensen, Keld A.; Wallin, Håkan; Nielsen, Gunnar D.; Koponen, Ismo K.

doi:10.1080/17435390.2016.1202350

Cited by 79Nanoparticles: synthesis and applicationsImmunotoxicology and immune responsesOccupational and environmental lung diseases

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Airway irritation, inflammation, and toxicity in mice following inhalation of metal oxide nanoparticles

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Larsen, Søren T., Jackson, Petra, Poulsen, Steen S., Levin, Marcus, Jensen, Keld A., Wallin, Håkan, Nielsen, Gunnar D., Koponen, Ismo K.·2016·Nanotoxicology

DOI 10.1080/17435390.2016.1202350PMC PMC5020351

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Abstract

Metal oxide nanoparticles are used in a broad range of industrial processes and workers may be exposed to aerosols of the particles both during production and handling. Despite the widespread use of these particles, relatively few studies have been performed to investigate the toxicological effects in the airways following inhalation. In the present study, the acute (24 h) and persistent (13 weeks) effects in the airways after a single exposure to metal oxide nanoparticles were studied using a murine inhalation model. Mice were exposed 60 min to aerosols of either ZnO, TiO2, Al2O3 or CeO2 and the deposited doses in the upper and lower respiratory tracts were calculated. Endpoints were acute airway irritation, pulmonary inflammation based on analyses of bronchoalveolar lavage (BAL) cell composition, DNA damage assessed by the comet assay and pulmonary toxicity assessed by protein level in BAL fluid and histology. All studied particles reduced the tidal volume in a concentration-dependent manner accompanied with an increase in the respiratory rate. In addition, ZnO and TiO2 induced nasal irritation. BAL cell analyses revealed both neutrophilic and lymphocytic inflammation 24-h post-exposure to all particles except TiO2. The ranking of potency regarding induction of acute lung inflammation was Al2O3 = TiO2 < CeO2 ≪ ZnO. Exposure to CeO2 gave rise to a more persistent inflammation; both neutrophilic and lymphocytic inflammation was seen 13 weeks after exposure. As the only particles, ZnO caused a significant toxic effect in the airways while TiO2 gave rise to DNA-strand break as shown by the comet assay.

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Available in vivo studies on CeO2 nanoparticles confirm the induction of inflammation after inhalation.
“Available in vivo studies on CeO2nanoparticles confirm the induction of inflammation after inhalation [3, 6, 17, 22–26].”
From Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats (2017) · cites this paper as [25]
Larsen et al. examined short-term exposure to metal oxide nanoparticles including CeO2 and detected signs of DNA damage in lung tissue only after TiO2 inhalation.
“Larsen et al. [25] examined short-term exposure to a group of metal oxide nanoparticles including CeO2 and detected signs of DNA damage in lung tissue only after TiO2 inhalation.”
From Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats (2017) · cites this paper as [25]

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Research Metal Oxide Nanoparticles Induce Unique Inflammatory Footprints in the Lung: Important Implications for Nanoparticle Testing
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Authors: Larsen, S. T., Jackson, P., Poulsen, S. S., Levin, M., Jensen, K. A., Wallin, H., Nielsen, G. D., & Koponen, I. K.
Affiliations: National Research Centre for the Working Environment (DK)
University of Copenhagen (DK)
Corresponding author: Larsen, Søren T.
ORCID: Larsen, Søren T.
Poulsen, Steen S.
Levin, Marcus
Jensen, Keld A.
Wallin, Håkan
Koponen, Ismo K.
Venue: Nanotoxicology
Publisher: Informa UK Limited
Published: 2016-07-18
Volume: 10
Issue: 9
Pages: 1254-1262
ISSN: 1743-5390 (ISSN-L)
1743-5404
DOI: 10.1080/17435390.2016.1202350
PMC: PMC5020351
OpenAlex: W2468155482
Cited by: 79
References: 39
Citations by year: 2026: 1 · 2025: 2 · 2024: 9 · 2023: 9 · 2022: 8 · 2021: 7 · 2020: 10 · 2019: 13 · 2018: 9 · 2017: 9 · 2016: 2
FWCI: 4.90
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Nanotoxicology (publishedVersion, cc-by-nc-nd)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc-nd)
Figshare (submittedVersion, cc-by)
Figshare (cc-by)
Topics: Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
Keywords: metal oxide nanoparticles, respiratory irritation, lung inflammation, pulmonary toxicity, zinc oxide, titanium dioxide, alumina, cerium oxide, nasal irritation, DNA damage, bronchoalveolar lavage, respiratory tract deposition, occupational exposure
MeSH terms: Aerosols, Animals, Bronchoalveolar Lavage Fluid, Female, Irritants, Lung, Mice, Inbred BALB C, Oxides, Particle Size, Pneumonia, Respiratory Function Tests, Inhalation Exposure, Respiratory Mucosa, Mice, Metal Nanoparticles

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Airway irritation, inflammation, and toxicity in mice following inhalation of metal oxide nanoparticles

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