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28 reviewsABSTRACTKeywords:8:2 Chlorinated polyfluoroalkyl ether sulfonate (8:2 Cl-PFESA) is a substitute for perfluorooctane sulfonate and 8:2 chlorinated polyfluoroalkyl ether sulfonatean emerging environmental pollutant, yet its bioaccumulation and health risks are poorly understood. We Accumulationestablished a subchronic exposure model in mice (0.04, 0.2, and 1 mg/kg/d) to evaluate its adverse effects. Our Hepatotoxicityfindings show extensive distribution of 8:2 Cl-PFESA in various tissues (plasma, liver, kidney, brain, heart, lung, Multi-omicstestis, ovary, spleen, thymus, thyroid, uterus, large intestine, small intestine, muscle, and fat), with the highest Amino acid metabolismaccumulation in the liver, identified as the primary storage organ. Liver histopathology revealed elevated alanine aminotransferase levels, reduced triglycerides, and ballooning degeneration. Proteomics analysis indicated