Phthalate mixture exposure is associated with oxidative imbalance in postmenopausal women: a cross-sectional study using WQS, qgcomp, and BKMR.

Phthalates are widespread environmental contaminants known for their endocrine-disrupting properties. Due to the decline in estrogen's antioxidant effects, postmenopausal women may be particularly vulnerable to oxidative stress; however, the effect of phthalate mixture exposure on systemic redox balance in this population remains uncertain. This study aimed to investigate the associations between urinary phthalate metabolites and oxidative balance score (OBS) among postmenopausal women and to identify major contributors within phthalate mixtures. We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Urinary concentrations of five phthalate metabolites measured via HPLC-ESI-MS/MS as part of the NHANES laboratory protocols, and the OBS derived by integrating both pro-oxidant and antioxidant factors, were used in the present analysis. Single-pollutant models, restricted cubic spline models, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were employed to assess individual and joint mixture effects while adjusting for sociodemographic, lifestyle, and clinical covariates. Higher urinary levels of certain phthalate metabolites, particularly mono-n-butyl phthalate (MBP) and mono-(2-ethylhexyl) phthalate (MEHP), were significantly associated with lower OBS, suggesting increased oxidative stress. Mixture models (WQS, qgcomp, and BKMR) consistently showed robust inverse associations between phthalate mixture exposure and oxidative balance. MBP and MEHP were identified as predominant contributors to the adverse oxidative effects. These associations remained robust across multiple sensitivity analyses. Our findings suggest that exposure to phthalate mixtures, notably MBP and MEHP, is linked to oxidative imbalance in postmenopausal women. These results highlight the importance of considering chemical mixtures in environmental health research and underscore the need for longitudinal studies to confirm causality and elucidate underlying mechanisms.