Nontargeted Urinary Profiling Strategy for Endocrine-Disrupting Chemicals in Women with Ovarian Malignancies

Endocrine-disrupting chemicals (EDCs), including known and unknown parent compounds, their metabolites, and transformation products, are pervasive in daily life, posing increasing risks to human health and the environment. This study employed a high-resolution mass spectrometry-based nontargeted screening approach, integrating polar (HILIC) and reversed-phase separations to expand the chemical space coverage and, supported by open-science tools and resources, evaluated urinary chemical profiles to assess internal EDC exposure. Among 106 annotated biomarkers of exposure, six exhibited significantly higher normalized intensities in patients with ovarian malignancies compared to healthy controls (<i>p</i> < 0.05). This suggests their greater exposure to phthalates (diethylhexyl phthalate and diethyl phthalate), pesticides (metolachlor metabolite and 4-nitrophenol), a UV filter (benzophenone-1), and an industrial byproduct (4-methyl-2-nitrophenol). These compounds may interfere with hormonal regulation, potentially contributing to cancer development. While these findings highlight potential differences in internal EDC exposure, the study primarily demonstrates the applicability of nontargeted urinary profiling for chemical exposure assessment. By providing new insights into EDCs burden and its pathological implications, this work contributes to advancing next-generation chemical risk assessment within the European Partnership for the Assessment of Risks from Chemicals initiative and supports the development of preventive strategies to mitigate environmental cancer risks.