Food-Associated Phthalate Exposure and Health Risk: Insights from Urinary Biomonitoring and Dose-Response Modeling

Phthalate acid esters (PAEs) are ubiquitous endocrine-disrupting chemicals with oxidative potential. While diet is a major exposure pathway, especially for high-molecular-weight PAEs, the contribution of specific food categories to internal doses and their subsequent impact on oxidative stress remain inadequately quantified. In this cross-sectional study of 327 adults, we measured 14 urinary monoester metabolites (mPAEs) and linked them with 24 h dietary records and oxidative stress biomarkers. Monoethyl phthalate was the most abundant metabolite (median: 37.8 μg/g creatinine (Cre)), followed by the summed metabolites of di(2-ethylhexyl) phthalate (∑5DEHP, 21.7 μg/g Cre). Redundancy analysis showed that the diet accounted for 33.6% of urinary mPAEs variance, with meat, poultry, protein-rich foods, and staples as major contributors. In mixture-based models, monobenzyl, monobutyl, and mono(2-ethyl-5-hydroxyhexyl) phthalates were identified as key drivers of oxidative damage to DNA (8-oxo-7,8-dihydro-2'-deoxyguanosine), lipids (malondialdehyde), and proteins (dityrosine). Furthermore, nonlinear dose-response patterns were observed, with steeper increases in risk at low-to-moderate exposures. Cumulative risk assessment revealed that 7.3% of individuals exceeded safety thresholds, primarily due to di-n-butyl phthalate and DEHP. Our findings emphasize the value of integrating dietary data in exposure assessment and support incorporating mixture effects and nonlinearity into PAEs risk evaluation and food safety governance.