Urinary Glyphosate and Oxidative DNA Damage, Lipid Peroxidation, and Prostaglandin-Related Biomarkers in Taiwanese Adults: A Cross-Sectional Analysis

Abstract Human epidemiological evidence linking glyphosate exposure to oxidative stress remains limited, particularly in adult general-population settings and in studies evaluating multiple oxidative stress biomarkers. We conducted a cross-sectional analysis of 1,030 adults from the Young Taiwanese Cohort (YOTA) in Taiwan. Urinary glyphosate and a panel of oxidative stress biomarkers were quantified by liquid chromatography–tandem mass spectrometry (LC–MS/MS), including 8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-iso-PGF2α), 2,3-dinor-8-iso-prostaglandin F2α (2,3-dinor-8-iso-PGF2α), prostaglandin F2α (PGF2α), 13(S)-hydroxyoctadecadienoic acid [13(S)-HODE], and the 8-iso-PGF2α/PGF2α ratio. The mean age was 33.45 years. The median and geometric mean urinary glyphosate concentrations were both 0.11 μg/L before and 0.12 μg/L after standardization to the median urinary specific gravity. In the fully adjusted model, each 1-unit increase in ln-transformed urinary glyphosate was associated with a 13.39% increase in 2,3-dinor-8-iso-PGF2α (95% CI: 4.45, 23.10) and a 17.62% increase in PGF2α (95% CI: 9.15, 26.74), whereas the 8-iso-PGF2α/PGF2α ratio decreased by 11.88% (95% CI: −19.47, −3.59). Associations with 8-OHdG and 8-iso-PGF2α were not statistically significant. A weaker positive association was observed for 13(S)-HODE [6.54% (95% CI: 0.39, 13.08)], but it did not remain statistically significant after correction for multiple comparisons. Restricted cubic spline (RCS) analyses provided no evidence of significant nonlinearity, and the overall pattern of findings was generally similar across sensitivity analyses addressing extreme exposure values, cardiometabolic conditions, BMI adjustment, dietary factors, and the molar sum of urinary di(2-ethylhexyl) phthalate (DEHP) metabolites. In conclusion, higher urinary glyphosate concentrations were associated most consistently with selected lipid-derived biomarkers, particularly 2,3-dinor-8-iso-PGF2α and PGF2α, together with a lower 8-iso-PGF2α/PGF2α ratio. These cross-sectional associations establish neither causality nor biomarker-specific mechanisms, do not exclude broader oxidative effects, and warrant confirmation in longitudinal studies with repeated measurements.