Associations of phthalate and phthalate alternative metabolites in urine with the risk of gallstones in adults: a cross-sectional analysis

It remains unclear whether phthalates are associated with gallstones and whether the associations of phthalate alternatives with gallstones are different from traditional phthalates. In this study, 1735 participants from the NHANES 2017-2018 were included and their urine was used to detect phthalate metabolites. We used logistic and restricted cubic spline regressions to assess individual associations and dose-response relationships between phthalate metabolites and gallstones, quantile g-computation and Bayesian kernel machine regression to assess mixed associations of phthalate metabolites with gallstones, and subgroup analyses to explore potential effect modifiers. We observed that individual associations of cyclohexane-1,2-dicarboxylic acid-mono(carboxyoctyl) ester phthalate (MCOCHP) (OR: 1.423, 95% CI: 1.098-1.844) and cyclohexane 1,2-dicarboxylic acid monohydroxy isononyl ester (MHNCH) (OR: 1.380, 95% CI: 1.080-1.763) with gallstones were linearly positive, mixed association of phthalate metabolites (OR: 2.453, 95% CI: 1.054-5.708) with gallstones was also positive, and MCOCHP and MHNCH had positive weights. The associations of phthalate metabolites with gallstones were higher in the males and participants with age ≥ 60 years, BMI ≥ 30 kg/m², hypertension, and diabetes. MCOCHP and MHNCH had the highest groupPIP (groupPIP: 0.941), mono(2-ethyl-5-carboxypentyl) terephthalate (MECPTP) had the highest condPIP (condPIP: 0.721), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), MCOCHP, and mono-isobutyl phthalate (MiBP) also had high condPIPs (condPIP > 0.5). The trend in mixed associations of phthalate metabolites with gallstones was positive. Our study suggests that traditional phthalates and phthalate alternatives are associated with gallstones, especially in the elderly, men, obese, hypertensive populations, and diabetic populations, and phthalate alternatives are associated with a higher risk of gallstones.