Skin toxicity of liquid crystal monomers (LCMs): Mitochondrial dysfunction and metabolic dysregulation revealed by integrated multi-omics analysis

Liquid crystal monomers (LCMs), as core components of liquid crystal displays (LCDs), are emerging as environmental materials due to their widespread use and potential for human and ecological exposure. Even as inquiries pertaining to the environmental and health risks of LCMs are progressing, their direct toxic effects on human organs and ecosystems persist in being inadequately comprehended. The present research underscores the hazards entailed by prolonged LCMs exposure, with specific reference to skin cells and animal models, under daily exposure magnitudes. This study reveals that long-term LCMs exposure disrupts mitochondrial function in skin cells, triggers inflammatory pathways (TNF signaling), and downregulates critical proteins (PLOD2, DDIT4) and metabolites (ATP, glutathione), indicating oxidative stress and cellular dysfunction. In vivo experiments further demonstrate histopathological damage in mouse skin, including disordered skin appendages and adipose disorganization, highlighting LCMs' hazardous potential. Multi-omics analysis links LCMs exposure to diseases such as lung cancer and Alzheimer’s, while untargeted metabolomics identifies β -alanylleucine downregulation as a promising biomarker for LCM-induced toxicity. Given LCD e-waste growth, improper disposal releases LCMs, risking ecosystem bioaccumulation. These findings underscore the need for stricter regulation of LCMs throughout their lifecycle-from production to waste management-to mitigate ecological and health risks, with β -alanylleucine serving as a potential monitoring tool for environmental contamination. • In vitro experiments revealed that LCMs exposure impaired mitochondrial function in HaCaT cells in a time-dependent manner. • Activation of the TNF signaling pathway, along with significant downregulation of PLOD2, DNA damage-inducible DDIT4, and CE proteins. • Disruptions in the TCA cycle, glutathione metabolism, and purine metabolism, with downregulation of key metabolites. • β -alanylleucine was identified as a potential metabolic biomarker for LCMs-induced skin injury.