Exposure to metal oxide nanoparticles administered at occupationally relevant doses induces pulmonary effects in mice

Abstract

In spite of the great promises that the development of nanotechnologies can offer, concerns regarding potential adverse health effects of occupational exposure to nanoparticle (NP) is raised. We recently identified metal oxide NP in lung tissue sections of welders, located inside macrophages infiltrated in fibrous regions. This suggests a role of these NP in the lung alterations observed in welders. We therefore designed a study aimed to investigate the pulmonary effects, in mice, of repeated exposure to NP administered at occupationally relevant doses. We therefore chose four metal oxide NPs representative of those found in the welder’s lungs: Fe₂O₃, Fe₃O₄, MnFe₂O₄ and CrOOH. These NPs were administered weekly for up to 3 months at two different doses: 5 μg, chosen as occupationally relevant to welding activity, and 50 μg, chosen as occupationally relevant to the context of an NP-manufacturing facility. Our results show that 3 month-repeated exposures to 5 μg NP induced limited pulmonary effects, characterized by the development of a mild peribronchiolar fibrosis observed for MnFe₂O₄ and CrOOH NP only. This fibrotic event was further extended in terms of intensity and localization after the repeated administration of 50 μg NP: all but Fe₂O₃ NP induced the development of peribronchiolar, perivascular and alveolar fibrosis, together with an interstitial inflammation. Our data demonstrate for the first time a potential risk for respiratory health posed by repeated exposure to NP at occupationally relevant doses. Given these results, the development of occupational exposure limits (OELs) specifically dedicated to NP exposure might therefore be an important issue to address.

• Nanoparticles
• occupationally relevant dose
• pulmonary effect
• occupational exposure limit
• welding fume

Acknowledgements

Mirlande Présumé was a fellow from Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail (ANSES) and Agence de l’Environnement et de la Maîtrise de l’Énergie (ADEME). Angélique Simon-Deckers and Grégory Beaune were both fellows from ANR. Sophie Lanone and Jorge Boczkowski were both recipients of a Contrat de Recherche Translationnelle, between Inserm and CHI Créteil (SL), or CHU Mondor (JB).

Declaration of interest

The authors declare that they have no competing interests.

This work was supported by funds from INSERM, Agence Nationale de la Recherche (grant ANR-09-CESA-017), Université Paris Est-Créteil, Chancellerie des Universités de Paris (Legs POIX), Fonds de Dotation-Recherche en Santé Respiratoire (SPLF), and C’Nano (grant AAP09-NanoSoud). This work also received the support from Labex SERENADE 11-LABX-0064 and DHU A-TVB (Département Hospitalo-Universitaire Ageing-Thorax-Vessel-Blood).

Supplementary material available online