Associations between urinary phthalate and benzophenone metabolites and early puberty timing in girls

Phthalates (PAEs) and benzophenones (BPs) are ubiquitous endocrine-disrupting chemicals, and exposure to them is thought to disrupt pubertal development. However, epidemiological evidence regarding their real-world, combined associations with early puberty timing (EPT) in girls remains limited and inconsistent. This case-control study enrolled a total of 147 girls, comprising 63 EPT cases and 84 healthy controls. Urinary concentrations of seven PAE and two BP metabolites were quantified. Single-pollutant associations and exposure-response relationships were evaluated using multivariable logistic regression and restricted cubic splines (RCS). To investigate potential modification of these associations by weight status, we conducted subgroup analyses. Furthermore, the overall joint association of the chemical mixture was quantified applying Bayesian kernel machine regression (BKMR) and quantile g-computation (Qgcomp). In single-pollutant models, MnBP, BP-8, MODP, and MMP were positively associated with the risk of EPT. Stratified analyses indicated that these associations remained consistent across different weight strata, with no significant interaction by weight status. In multi-pollutant analyses, Qgcomp revealed a significant positive joint association of the chemical mixture with EPT (OR=1.36; 95% CI: 1.12, 1.65), which was consistently supported by the BKMR models. Notably, MnBP and BP-8 emerged as the primary contributors of this combined association. Our findings highlight that co-exposure to specific PAE and BP metabolites, particularly MnBP and BP-8, is positively associated with EPT in girls. Future prospective cohorts are necessary to validate these results and uncover the biological pathways.