Synergistic exposure to endocrine-disrupting chemicals in pediatric lungs: Epidemiological drivers and...

This study examined 79 endocrine-disrupting chemicals (EDCs) in 99 normal and 53 paired malformed pediatric lung tissues with congenital pulmonary airway malformation (CPAM). In normal tissues, 35 EDCs were identified in over 50 % of cases. The most abundant compounds were phthalates (216-9395 ng g^-1 ww) and their metabolites (24.1-421 ng g^-1 ww), followed by organophosphate esters (66.4-2678 ng g^-1 ww) and their metabolites (14.2-283 ng g^-1 ww). Other EDCs with detection frequencies higher than 50 % included 3 parabens, 2 bisphenols, 2 alkylphenols, benzophenone-3, and triclosan, indicating a complex exposure scenario in pediatric lungs. Although only four targeted EDCs might pose gender-specific risks, more than half of these EDCs exhibited age or developmentally dependent distribution patterns, highlighting the impacts of physiological factors on EDC exposure in children. Besides, 20 out of 35 EDCs differed significantly between normal and adjacent malformed tissues, with 17 elevated in malformed tissues (p < 0.05). Transcriptome analysis was performed in 8 samples and identified 62 differentially expressed genes associated with CPAM. Exposure levels of 19 out of 20 EDCs correlated significantly with these genes, which may be involved in pathways of chemical carcinogenesis, cytokine and hormone signaling. These findings highlight the vulnerability of pediatric lungs to EDC mixtures and emphasize the need for exploration the underlying mechanisms of EDC exposure in respiratory diseases in children.