Associations Between Organophosphate Esters Exposure and Metabolic Syndrome: Exploring the Mediating Role of Oxidative Stress and Inflammation in Adults

Abstract Epidemiological evidence regarding the relationships of organophosphate esters (OPEs) with metabolic syndrome (MetS) and its underlying mechanism was largely unknown. This study sought to estimate the correlations of individual OPEs and their mixture with MetS risk, while also evaluating the potential mediation of oxidative stress and inflammation biomarkers. We measured urinary OPE metabolites, urinary biomarkers of oxidative stress, and serum biomarkers of inflammation among 694 adults based on a case-control design. Our findings revealed positive correlations between urinary 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and bis(2-butoxyethyl) phosphate (BBOEP) and elevated odds of MetS risk. Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) analyses demonstrated the overall effect of the OPE mixtures on MetS risk, with BBOEP identified as the primary contributor. Mediation analysis further revealed that the association between urinary BCIPHIPP and BBOEP and MetS risk was mediated by urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), with mediation proportions of 23.27% and 8.70%, respectively. In addition, serum C-reactive protein (CRP) concentration mediated the association between BBOEP and MetS risk, and the proportion of mediation was 16.32%. Our results indicated that oxidative stress and inflammation might exert a substantial influence on the correlations between OPE exposure and the risk of MetS.