Benzophenones exposure and precocious puberty in Chinese children: A case-control study

Benzophenones (BPs), widely used as ultraviolet filter in personal care products, were potential endocrine disruptors. However, epidemiological data of BPs exposure with precocious puberty (PP), one of the most common endocrine disorder in children, remain limited. This case-control study, conducted at Wuhan Children's Hospital with 298 clinically diagnosed PP cases and 1:1 matched (n = 298) controls, aims to assess the associations between BPs exposure and PP. Urinary concentrations of five BPs were measured using ultra‑performance liquid chromatography‑tandem mass spectrometry (UPLC‑MS/MS). Detection frequencies of 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3) reached 100% and 96%, respectively. Conditional logistic regression analyses revealed that higher exposure levels of BP-1 (Q2-Q4) were associated with PP, with odds ratios (ORs) and 95% CIs of 2.30 (1.33-3.97), 1.78 (1.06-2.98), and 1.80 (1.08-3.01), compared with the lowest exposure quartile (Q1),. Higher levels of BP-3 and 4-OH-BP were also significantly associated with PP. When stratified by subtypes of PP, we observed similar associations in children with central precocious puberty (CPP), but not in those with rapidly progressive puberty (RPP) or partial central precocious puberty (PCPP). BKMR analysis further suggested that co-exposure to multiple BPs was associated with increased odds of PP, particularly CPP. These findings suggest a potential association between BP exposure and childhood pubertal development, warranting prospective studies to confirm temporality and evaluate BP exposure as a possible risk factor for PP.