Effects of organochlorine pesticides (OCPs) on adolescent body composition: Integrating epidemiology and bioinformatics

Exposure to organochlorine pesticides (OCPs) may disrupt adolescent development; however, their precise impacts remain unclear. Using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016, we examined associations between OCPs and adolescent body composition indicators, including body mass index (BMI) z_score, appendicular lean mass (ALM), trunk fat (TRF), total fat (TOF), total lean mass (TLM), and total percent fat (TPF). We fitted several statistical models including linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Mediation analysis evaluated the effect of serum albumin, while network toxicology and molecular docking identified key targets and pathways. Linear regression showed that OCPs were negatively correlated with BMI z_score, ALM, TRF, TOF, TLM, and TPF in adolescents, particularly in males. The WQS and BKMR revealed a negative relationship between OCPs mixtures and BMI z_score, TRF, TOF, and TPF, with hexachlorobenzene (HCB) as the major contributor. Albumin mediated the negative effects of HCB on all body composition indicators. Preliminary bioinformatics analyses suggested that HCB may influence body composition through inflammation, metabolic regulation, and apoptosis involving the MAPK, PI3K-Akt, and Ras signaling pathways. These findings suggest that HCB exposure may adversely affect adolescent growth and nutritional health, particularly among males.