Environmental relevant concentrations of TBBPA cause complex toxicological mechanisms.

Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant recognized for its environmental persistence, bioaccumulation and toxicological potential, raising concerns about its hazardous effects on both ecological systems and human health. Our research investigated the hepatotoxicity of TBBPA at environmentally relevant concentrations (1-100 nM) using transformed human liver epithelial-2 (THLE-2) cells. Results demonstrated that TBBPA exposure induced cell alterations in cell density, nuclear irregularities and fibrosis-like extensions. Transcriptomic analysis revealed significant perturbations in pathways related to metabolism, cellular stress responses, inflammatory responses, cell proliferation, substance transport and degradation. Further investigations revealed the most obvious gene expression profile changes at 1 nM TBBPA exposure, however, higher concentrations (10 nM and 100 nM) of TBBPA appeared to cause more severe hepatotoxicity. RT-qPCR and molecular docking experiments confirmed the changed gene expression and TBBPA-Protein binding. These findings elucidate complex mechanisms of TBBPA-induced effects in hepatocytes, highlighting the environmental health risks of TBBPA.