Toxicological Assessment of ITER-Like Tungsten Nanoparticles Using an In Vitro 3D Human Airway Epithelium Model

Isabelle George (1) , Chiara Uboldi (2) , Elodie Bernard (3) , Marcos Sanles Sobrido (4) , Sarah Dine (5) , Agnès Hagège (6) , Dominique Vrel (5) , Nathalie Herlin (7) , Jérôme Rose (4) , Thierry Orsiere (2) , Christian Grisolia (3) , Bernard Rousseau (1) , Veronique Malard (8, 9)

1 SCBM - Service de Chimie Bio-Organique et de Marquage
2 IMBE - Institut méditerranéen de biodiversité et d'écologie marine et continentale
3 IRFM - Institut de Recherche sur la Fusion par confinement Magnétique
4 CEREGE - Centre européen de recherche et d'enseignement des géosciences de l'environnement
5 LSPM - Laboratoire des Sciences des Procédés et des Matériaux
6 TechSep - Separative Methods - Techniques séparatives
7 LEDNA - Laboratoire Edifices Nanométriques
8 BIAM - Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB)
9 IPM - Interactions Protéine Métal

The International Thermonuclear Experimental Reactor (ITER) is an international project aimed at the production of carbon-free energy through the use of thermonuclear fusion. During ITER operation, in case of a loss-of-vacuum-accident, tungsten nanoparticles (W-NPs) could potentially be released into the environment and induce occupational exposure via inhalation. W-NPs toxicity was evaluated on MucilAir™, a 3D in vitro cell model of the human airway epithelium. MucilAir™ was exposed for 24 h to metallic ITER-like milled W-NPs, tungstate (WO$_4$$^{2−}$) and tungsten carbide cobalt particles alloy (WC-Co). Cytotoxicity and its reversibility were assessed using a kinetic mode up to 28 days after exposure. Epithelial tightness, metabolic activity and interleukin-8 release were also evaluated. Electron microscopy was performed to determine any morphological modification, while mass spectrometry allowed the quantification of W-NPs internalization and of W transfer through the MucilAir™. Our results underlined a decrease in barrier integrity, no effect on metabolic activity or cell viability and a transient increase in IL-8 secretion after exposure to ITER-like milled W-NPs. These effects were associated with W-transfer through the epithelium, but not with intracellular accumulation. We have shown that, under our experimental conditions, ITER-like milled W-NPs have a minor impact on the MucilAir™ in vitro model.

Keywords: MucilAir™; lung; nanoparticles; acute toxicity; tungsten

Domains: Material chemistry; Toxicology

Isabelle George, Chiara Uboldi, Elodie Bernard, Marcos Sanles Sobrido, Sarah Dine, et al.. Toxicological Assessment of ITER-Like Tungsten Nanoparticles Using an In Vitro 3D Human Airway Epithelium Model. Nanomaterials, 2019, 9 (10), pp.1374. ⟨10.3390/nano9101374⟩. ⟨cea-02302666⟩