Toxicity of tungsten and molybdenum disulphide particles after acute and subacute exposure in vitro

Tungsten (W) and molybdenum disulphide (MoS₂) particles are increasingly used industrially, but may pose potential health risks, particularly following inhalation in occupational settings. Existing data is inconsistent but there is evidence that these particles are genotoxic. Therefore, there is a need to further increase our understanding on their toxicity and underlying mechanisms. To this end, we tested W and MoS₂ particles in two human cell models, in vitro bronchial epithelial cells (BEAS-2B) and monocyte-derived macrophages (dTHP-1) after acute exposure (24 h), but we also investigated effects after subacute (2-week) exposure of BEAS-2B cells. We evaluated cellular metal content (by ICP-MS), cytotoxicity (by Alamar Blue and Trypan Blue), DNA damage (by alkaline comet assay) and secretion of pro-inflammatory cytokines (IL-6, IL-8/CXCL8, IL-1ß, TNF-α by multiplex electrochemiluminescence) into cell media. After acute exposure, both particles induced dose-dependent DNA damage in BEAS-2B and dTHP-1 cells. In addition, W particles also increased secretion of cytokines from dTHP1, while none were significantly increased in BEAS-2B cells. After subacute exposure both particles increased IL-6 secretion from BEAS-2B cells and induced dose-dependent DNA damage, which remained persistent at 1 week of recovery. Overall, our data indicate that MoS₂ and W are genotoxic, likely via different mechanisms. The data suggest that exposure duration did not influence genotoxicity in BEAS-2B, but was important for inflammatory responses. When compared with in vivo data, our cell models predicted genotoxicity in bronchoalveolar lavage cells well and, to some extent, also lung inflammation. Finally, these findings stress the importance of limiting occupational exposure to W and MoS₂ to protect workers' health.