Exposure to metal oxide nanoparticles administered at occupationally relevant doses induces pulmonary effects in mice.
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, MnFe2O4and 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 MnFe2O4and 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 Fe2O3NP 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.
a INSERM, U955, Team4 , Créteil , France.
Mirlande
M
Présumé
a INSERM, U955, Team4 , Créteil , France.|b CNRS, UMR 8502, Laboratoire de Physique des Solides , Orsay , France.
Angélique
A
Simon-Deckers
c INSERM, UMR-S1124, Toxicologie Pharmacologie et Signalisation cellulaire , Paris , France.|d Université Paris Descartes , Paris , France.
Céline
C
Tomkiewicz-Raulet
c INSERM, UMR-S1124, Toxicologie Pharmacologie et Signalisation cellulaire , Paris , France.
Béatrice
B
Le Grand
e APHP, CHU Henri Mondor, Service d'Anatomo-Pathologie , Créteil , France.|f Université Paris-Est Créteil, Faculté de Médecine , Créteil , France.
Jeanne
J
Tran Van Nhieu
g Sorbonne Universités, UPMC Université Paris 06, CNRS, Collège de France, Laboratoire de Chimie de la Matière Condensée de Paris , Paris , France.
Gregory
G
Beaune
g Sorbonne Universités, UPMC Université Paris 06, CNRS, Collège de France, Laboratoire de Chimie de la Matière Condensée de Paris , Paris , France.
Olivier
O
Duruphty
b CNRS, UMR 8502, Laboratoire de Physique des Solides , Orsay , France.
Jean
J
Doucet
c INSERM, UMR-S1124, Toxicologie Pharmacologie et Signalisation cellulaire , Paris , France.|d Université Paris Descartes , Paris , France.
Xavier
X
Coumoul
a INSERM, U955, Team4 , Créteil , France.|f Université Paris-Est Créteil, Faculté de Médecine , Créteil , France.|h Centre Hospitalier Intercommunal de Créteil, Service de Pneumologie et Pathologie professionnelle , Créteil , France , and.
Jean-Claude
JC
Pairon
a INSERM, U955, Team4 , Créteil , France.|f Université Paris-Est Créteil, Faculté de Médecine , Créteil , France.|i APHP, DHU A-TVB, CHU Henri Mondor, Service d'Explorations fonctionnelles respiratoires , Créteil , France.
Jorge
J
Boczkowski
a INSERM, U955, Team4 , Créteil , France.|h Centre Hospitalier Intercommunal de Créteil, Service de Pneumologie et Pathologie professionnelle , Créteil , France , and.
Sophie
S
Lanone
a INSERM, U955, Team4 , Créteil , France.|f Université Paris-Est Créteil, Faculté de Médecine , Créteil , France.|h Centre Hospitalier Intercommunal de Créteil, Service de Pneumologie et Pathologie professionnelle , Créteil , France , and.
Pascal
P
Andujar
D000818:Animals; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D010087:Oxides / Q000633:toxicity; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D014896:Welding
D010087:Oxides
Nanoparticles; occupational exposure limit; occupationally relevant dose; pulmonary effect; welding fume