Identification and Characterization of Key Hazardous Substances in Precocious Puberty Children: An Internal Exposure Assessment in China’s Typical Coastal Cities

Epidemiological studies indicate associations between exposures to endocrine-disrupting chemicals (EDCs) with reproductive disorders (e.g., early puberty). However, the scientific evidence remains limited, particularly in studies on clinically diagnosed precocious puberty (PP), and the specific pollutant drivers underlying this condition are poorly characterized. Identifying the key hazardous substances contributing to PP thus represents a critical research priority. This study conducted a population-based case–control study to profile the internal exposure to organic pollutants. Using a combination of liquid–liquid extraction (LLE) and solid-phase extraction, we performed suspect screening and nontargeted analysis with high-resolution mass spectrometry (HRMS) (liquid chromatography-/GC-Orbitrap HRMS). Nontargeted analysis revealed a broad spectrum of EDCs, including polycyclic aromatic hydrocarbons, phthalate esters (PAEs), organophosphate esters (OPEs), phenols, amides, and acrylates. Differential analysis between cases and controls further highlighted several pollutant classes, such as organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFAS), phenols, and chlorinated paraffins. These pollutants were significantly elevated in the PP group. These findings provide new internal exposure data and methodological support for environmental health research. They also offer a scientific foundation for targeted source–control strategies to reduce children’s exposure to harmful pollutants, supporting the broader public health objectives of “Healthy China 2030”.