Mechanistic study of C₅F₁₀O-induced lung toxicity in rats: An eco-friendly insulating gas alternative to SF₆

The global warming and other environmental problems caused by SF₆ emissions can be reduced due to the widespread use of eco-friendly insulating gas, perfluoropentanone (C₅F₁₀O). However, there is an exposure risk to populations in areas near C₅F₁₀O equipment, so it is important to clarify its biosafety and pathogenesis before large-scale application. In this paper, histopathology, transcriptomics, 4D-DIA proteomics, and LC-MS metabolomics of rats exposed to 2000 ppm and 6000 ppm C₅F₁₀O are analyzed to reveal the mechanisms of toxicity and health risks. Histopathological shows that inflammatory cell infiltration, epithelial cell hyperplasia, and alveolar atrophy accompanied by alveolar wall thickening are present in both low-dose and high-dose groups. Analysis of transcriptomic and 4D-DIA proteomic show that Cell cycle and DNA replication can be activated by both 2000 ppm and 6000 ppm C₅F₁₀O to induce cell proliferation. In addition, it also leads to the activation of pathways such as Antigen processing and presentation, Cell adhesion molecules and Complement and coagulation cascades, T cell receptor signal path, Th1 and T cell receptor signal path, Th1 and Th2 cell differentiation, complement and coagulation cascades. Finally, LC-MS metabolomics analysis confirms that the metabolic pathways associated with glycerophospholipids, arachidonic acid, and linoleic acid are disrupted and become more severe with increasing doses. The mechanism of lung toxicity caused by C₅F₁₀O is systematically expounded based on the multi-omics analysis and provided biosafety references for further promotion and application of C₅F₁₀O.