Insights into Hepatotoxicity of Fluorinated Liquid Crystal Monomer 1-Ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) benzene (EDPrB) in Adult Zebrafish at Environmentally Relevant Concentrations: Metabolic Disorder and Stress Response

Fluorinated liquid crystal monomers (FLCMs) are widely employed in liquid crystal display (LCD) panels. As emerging environmental contaminants with persistent, bioaccumulative, and toxic properties, FLCMs were proven to accumulate in liver, raising great concern regarding potential hepatotoxicity. 1-Ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) benzene (EDPrB), as one representative FLCM, was chosen to investigate the hepatotoxicity in adult zebrafish (Danio rerio) at environmentally relevant concentrations (1, 10, and 100   μg/L) with long-term exposure (21 days). EDPrB caused morphological abnormalities, elevated transaminase activities, and inhibited antioxidant levels in zebrafish liver. The contents of total cholesterol and triglyceride were reduced by 2.3- and 1.82-fold, respectively, at 100   μg/L of EDPrB. Transcriptomic analysis revealed that EDPrB disrupted the lipid and glucose metabolisms, protein processing in endoplasmic reticulum (ER), and P53 signal pathway by dysregulating genes, such as fasn, acaca, acsl1b, hkdc1, xbp1, and ero1lb. EDPrB induced ER stress by activating PERK-eIF2α pathway, leading to hepatic metabolic dysfunction. PERK-eIF2α and P53-Bax/Bcl2 pathways were involved in EDPrB-induced apoptosis. Additionally, molecular simulation confirmed that EDPrB had a strong binding affinity to some lipid metabolism proteins (-8.9~-6.7   kcal/mol) and stress proteins (-9.3~-5.8   kcal/mol). The findings elucidate EDPrB-induced hepatotoxicity and underlying mechanisms, which contribute to assessing the ecological risk and pollution control of FLCMs.