Biosafety of two-dimensional molybdenum disulfide nanomaterials: Natural and engineered transformation pathways and their role in the toxicity profile

As a rising star in the post-graphene era, two-dimensional molybdenum disulfide nanomaterials (2D-MoS₂) are taking the scientific community by storm due to their fascinating physicochemical properties. An accurate and comprehensive understanding of the biosafety of 2D-MoS₂ is urgently needed before further translating its promising performance in laboratory scale studies into actual applications in practice. The toxicity of 2D-MoS₂ is highly correlated with their specific parameters, which means that artificial modifications or natural aging scenarios of 2D-MoS₂ should be included in the corresponding toxicological reports. In this review, we first critically review the toxicological data on 2D-MoS₂ obtained in various in vitro and in vivo toxicity evaluation models. Subsequently, we summarize the different approaches of modification and natural aging pathways of 2D-MoS₂, including size and layer structure changes, phase transformation, surface defects, bio-molecular hybridization, surface functionalization, etc. We further critically discuss how these transformations will affect the toxicity and mechanisms of interaction of 2D-MoS₂ with organisms, emphasizing the necessity of adopting interdisciplinary approaches to fully reveal the correlation between 2D-MoS₂ transformations and toxicity profile. Based on the critical review of existing studies, we identify current knowledge gaps and priorities for future research, highlighting the necessity of establishing exposure protocols with uniform criteria, developing precautionary toxicity mitigation strategies and predictive models, and incorporating transformation scenarios throughout the toxicity assessment procedures of 2D-MoS₂.