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OBJECTIVE Toxicity induced by exposure to bisphenol A (BPA) has been widely reported.Studying metabolites variation holds promise for the discovery of mechanisms linked to BPA toxic effects.METHODS AND RESULTS Male Sprague-Dawley rats were orally administered doses of BPA at the levels of 0, 0.0005, 50 mg· kg-1· d-1 for 8 weeks.We used unbiased liquid chromatography (LC)-time-of-flight (TOF) and capillary electrophoresis (CE)-TOF metabolomics technique to discover,identify and analyze the variation of metabolites in testes and urine, respectively.In rat testes, by using multiple approaches, we identified linoleic acid (LA) and arachidonic acid (AA), two n-6 fatty acids, as potential testicular biomarkers.Decreased levels of LA, increased levels of AA and AA/LA ratio in testes were observed in exposed group.According to these suggestions, the levels of testicular antioxidant enzymes were detected.Testicular superoxide dismutase (SOD) declined significantly compared with that of the control, and the glutathione peroxidase (GSH-Px) and catalase (CAT) also showed decreasing trend in BPA treated group.In rat urine, 199 named metabolites were profiled in rat urine.Various changes in metabolic pathways were observed including elevated nucleotide degradation, altered choline metabolism and vitamin metabolism.CONCLUSION BPA caused testicular n-6 fatty acid composition variation and decreased antioxidant capacity, which may be involved in its reproductive toxicity.The metabolic profiling in urine indicates that BPA exposure caused wide changes in lipid, nucleotide, carbohydrate and amino acid metabolism.This metabonomics study firstly showed the availability of metabolomic analysis in exploring BPA toxicity.