Indoor VOCs Exposure Disrupts Hemostatic Balance: Plasma Proteomics Identifies Complement and Coagulation Cascade Dysregulation as a Critical Signature.

Volatile organic compounds (VOCs) are prevalent indoor pollutants, posing significant health risks. However, current toxicological data focus predominantly on individual compounds, leaving a critical gap in understanding how exposure to mixed VOCs alters the plasma proteome and impacts health risk prediction. Herein, we investigated VOCs-induced hematological disturbances using a whole-body inhalation exposure model with C57BL/6J mice (n = 3) exposed to decoration-derived VOCs for 8 weeks. By integrating plasma proteomics with machine learning, we demonstrated that VOCs exposure significantly disrupts hemostatic homeostasis, primarily by perturbing the complement and coagulation cascades. Network enrichment and correlation analyses further identified a network of suppressed pathways (e.g., platelet activation and focal adhesion) and activated pathways (e.g., necroptosis and IL-17 signaling pathway) that collectively drive this dysregulation. Critically, we identified downregulated von Willebrand factor (VWF) and cell division control protein 42 (CDC42) as a robust biomarker signature, as evidenced by correlation coefficients (r) of 0.91 and 0.90 with complement and coagulation cascades, respectively. Leveraging these biomarkers, we developed a highly accurate health risk scoring model. This study provides the first comprehensive molecular portrait of VOCs-induced hematological disturbances and presents a novel proteomics-driven framework for the early prediction and intervention of VOCs-related health effects.