Exposomic Assessment of Endocrine-Disrupting Chemicals Using Hair: A Cross-Matrix Comparison with Serum and Urine by LC-HRMS and Metabolite Profiling

Abstract Endocrine-disrupting chemicals (EDCs) are increasingly implicated in chronic diseases, yet their biomonitoring in human studies still relies mainly on urine and serum, which capture only short-term exposure to these fast-elimination compounds. Here, we evaluated hair as a complementary and long-term biomonitoring matrix for EDC mixtures by integrating it into an LC-HRMS exposomics workflow together with paired serum and urine samples. We developed and validated a method targeting 44 endocrine disruptors from five chemical families (benzophenones, phthalates, parabens, bisphenols, and organophosphate esters), combining quantitative analysis with suspect screening and semi-quantification of phase II metabolites. Applied to samples from 20 postmenopausal women, the hair-based approach provided the broadest coverage and highest concentrations (31/44 compounds), up to about three orders of magnitude higher than in urine or serum, consistent with distinct accumulation mechanisms and temporal integration windows. In hair, EDCs were present in unconjugated form (>99%), whereas urine was dominated by conjugated metabolites and serum showed limited detection. Overall, these findings demonstrate that integrating hair into multimatrix exposomics designs substantially expands both the chemical and temporal resolution of human exposure assessment.