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

Abstract

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 (WO42−) 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.

A 3D In Vitro Model of the Human Airway Epithelium Exposed to Tritiated Water: Dosimetric Estimate and Cytotoxic Effects

“…A pro-inflammatory response is observed at day 1 and day 7 after exposure to the highest activity level, as indicated by the increase of IL-8 secretion. It is important to note that IL-8, though certainly not exhaustive of the inflammatory response pathway, was chosen as one of the most abundant pro-inflammatory mediators released by airway epithelial cells, shown to be upregulated by, e.g., nanoparticles of different kinds (19) including tungsten (8). This also makes it an ideal candidate for future adoption of this model for tritiated particles, as discussed later.…”

“…The MucilAir model mimics the upper respiratory tract structure of the human lung, including basal, goblet and ciliated cells. Representative TEM pictures of the tissue have been provided elsewhere, in our previously published work (8).…”

“…Such models have the potential to recapitulate toxicity responses through the respiratory function, when exposed to a variety of pathogens or chemicals (7). We recently used such a model to assess the toxicity of tritiated tungsten particles (8). To our knowledge, these models have never been adopted to investigate the effects of tritiated products.…”

Photocatalysis-mediated drug-free sustainable cancer therapy using nanocatalyst

“…It is noticeable that no NIR-irradiation did not trigger photocatalytic reactions and consequently did not cause toxicity to normal organs, and there was no toxic side effects of drug because no drug was used, reflecting the incomparable advantages of drug-free therapy in biosafety. Additionally, the toxicity of tungsten as a heavy metal is mainly demonstrated by soluble tungstates rather than by relatively more stable tungsten oxide and metal tungsten [40][41][42][43][44][45][46][47][48] , and therefore the development of tungsten oxide for biomedical applications is broadly being studies [42][43][44][45][46][47][48] where high biocompatibility with lowest toxic dose of 1000 mg/kg for oral administration was demonstrated. In this work, we also found that neither WO 3 nor SnS 1.68 -WO 2.41 exhibited obvious cytotoxicity (600 μg/mL, Supplementary Fig.…”

Design of an Inhalation Chamber and Metrology Assessment to Study Tungsten Aerosol Neurotoxic Effects

“…Experimental studies have demonstrated an increase in inflammation and oxidative stress processes as well as histological impairments in rodent lungs after exposure of upper airways to tungsten (Roedel et al, 2012;Prajapati et al, 2017). Very recently, using two in vitro models, BEAS-2B cells and 3D human airway epithelium model, differential responses to tungsten were documented: epigenotoxic alterations and transient inflammatory response (George et al, 2019;Uboldi et al, 2019).…”