Predicting pan-thyroid toxicity induced by combined exposure to tetrabromobisphenol A and tetrachlorobisphenol A: network toxicology analysis and molecular docking validation

This study investigates thyroid toxicity mechanisms of combined tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) exposure using integrative network toxicology and molecular docking. We identified shared targets between thyroid disorders (hyperthyroidism, thyroid cancer, Hashimoto’s thyroiditis, etc.) and TBBPA/TCBPA exposure. Protein-protein interaction network analysis prioritized core targets (TP53, AKT1, IL6, EGFR) with high centrality. Functional enrichment revealed significant associations with thyroid hormone signaling, PI3K-Akt, and cancer pathways, involving transcriptional regulation, xenobiotic response, and proliferation. Molecular docking demonstrated strong binding affinities of TBBPA/TCBPA to key targets via hydrogen bonding and hydrophobic interactions. Shared core targets and pathways across distinct thyroid disorders suggest interconnected molecular mechanisms. Our findings propose that TBBPA/TCBPA co-exposure may disrupt thyroid homeostasis by modulating apoptosis, inflammation, and hormone signaling, while revealing latent disease correlations. This work provides insights into the environmental etiology of thyroid disorders and a framework for assessing combined toxicant effects.