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BackgroundExposure to disinfection by-products (DBPs) in drinking water and chlorinated swimming pools are associated with adverse health outcomes, but biological mechanisms remain poorly understood.ObjectivesEvaluate short-term changes in metabolic profiles in response to DBP exposure while swimming in a chlorinated pool.Materials and methodsThe PISCINA-II study (EXPOsOMICS project) includes 60 volunteers swimming 40 min in an indoor pool. Levels of most common DBPs were measured in water and in exhaled breath before and after swimming. Blood samples, collected before and 2 h after swimming, were used for metabolic profiling by liquid-chromatography coupled to high-resolution mass-spectrometry. Metabolome-wide association between DBP exposures and each metabolic feature was evaluated using multivariate normal (MVN) models. Sensitivity analyses and compound annotation were conducted.ResultsExposure levels of all DBPs in exhaled breath were higher after the experiment. A total of 6,471 metabolic features were detected and 293 features were associated with at least one DBP in exhaled breath following Bonferroni correction. A total of 333 metabolic features were associated to at least one DBP measured in water or urine. Uptake of DBPs and physical activity were strongly correlated and mutual adjustment reduced the number of statistically significant associations. From the 293 features, 20 could be identified corresponding to 13 metabolites including compounds in the tryptophan metabolism pathway.ConclusionOur study identified numerous molecular changes following a swim in a chlorinated pool. While we could not explicitly evaluate which experiment-related factors induced these associations, molecular characterization highlighted metabolic features associated with exposure changes during swimming.Highlights•MWAS of exposure to Disinfection By-Products from swimming in a chlorinated pool•6471 metabolic features were detected by UHPLC-QTOF- Mass Spectrometry.•DBP exposures were measured in exhaled breath, urine and in swimming water.•293 metabolic features associated to at least one DPB, and 137 to all exposures•Annotation revealed 13 compounds involved in the tryptophan metabolism pathway.