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Background Through various sources the Chinese general population may exposed to arsenic.Urinary biomonitoring can provide the most accurate arsenic exposure assessment; however,to improve risk assessment,arsenic-related metabolic biomarker are required to understand internal processes that may be perturbed which may,in turn,link the exposure to a specific health outcome.Objectives The objective of this study is to investigate arsenic-induced metabolome changes and identify dose-dependent metabolic biomarkers.Methods Urinary arsenic species such as inorganic arsenic(iAs = iAsIII + iAsV),methylarsonic acid(MMA),dimethylarsinic acid(DMA)and arsenobetaine(AsB)were quantified using high performance liquid chromatography(HPLC)-inductively coupled plasma-mass spectrometry in a Chinese adult male cohort.Urinary metabolomics was conducted by using HPLC-quadrupole time of flight mass spectrometry(qTOF-MS).Arsenic-related metabolic biomarkers were investigated by comparing the samples of the 1st and 5th quintiles of arsenic exposure classifications using a partial least squares discriminant analysis model.Results After adjustment for age,body mass index,smoking and alcohol consumption,five potential biomarkers related to arsenic exposure(i.e.,testosterone,guanine,hippurate,acetyl-N-formyl-5-methoxykynurenamine(AFMK)and serine)were identified from 61 candidate metabolites; these biomarkers suggest endocrine disruption and oxidative stress are associated with urinary arsenic levels.Testosterone,guanine and hippurate showed high or moderate ability to discriminate the 1st and 5thquintiles of arsenic exposure with AUC 0.89,0.87 and 0.83,respectively; their combination pattern showed an AUC of 0.91 with sensitivity of 88%and specificity of 80%.Arsenic dose-dependent AUC changes were also observed.Conclusions This study demonstrated that metabolomics can be used to investigate arsenic-related biomarkers of metabolic changes; the dose-dependent trends of arsenic exposure to these biomarkers may translate into the use of metabolic biomarkers in arsenic risk assessment.As this was a proof-of-concept study,more research is needed to confirm the relationships we observed between arsenic exposure and biochemical changes.