In vitro analysis of the cytotoxic effect of two different sizes ITER-like tungsten nanoparticles on human dermal fibroblasts

Background: Based on the current configuration of the International Thermonuclear Experimental Reactor, tungsten (W) was chosen as the armour material. Nevertheless, during operation, the expected power and temperature of plasma can trigger the formation of W dust in the plasma chamber. According to the scenario for a Loss Of Vacuum Accident (LOVA), in the case of confinement failure dust is released, which can lead to occupational or accidental exposure.Methods: For a first evidence of potential risks, fusion devices relevant W dust has been produced on purpose, using a magnetron sputtering gas aggregation source. We aimed to assess the in vitro cytotoxicity of synthesized tungsten nanoparticles (W-NPs) with diameters of 30 and 100 nm, on human BJ fibroblasts. That was systematically investigated using different cytotoxic endpoints (metabolic activity, cellular ATP, AK release and caspase-3/7 activity) and by direct observation with optical and scanning electron microscopy.Results: Increasing concentrations of W-NPs of both sizes induced cell viability decrease, but the effect was significantly higher for large W-NPs, starting from 200 mu g/mL. In direct correlation with the effect on the cell membrane integrity, high concentrations of large W-NPs appear to increase AK release in the first 24 h of treatment. On the other hand, activation of the cellular caspase 3/7 was found significantly increased after 16 h of treatment solely for low concentra-tions of small W-NPs. SEM images revealed an increased tendency of agglomeration of small W -NPs in liquid medium, but no major differences in cells development and morphology were observed after treatment. An apparent internalization of nanoparticles under the cell membrane was also identified.Conclusion: These results provide evidence for different toxicological outputs identified as mechanistic responses of BJ fibroblasts to different sizes of W-NPs, indicating also that small W -NPs (30 nm) display lower cytotoxicity compared to larger ones (100 nm).