Childhood susceptibility to PFAS-associated endocrine disruption: NHANES age-stratified analysis and PFOS mouse model...

Mixed exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with altered male endocrine function, but age-specific susceptibility is uncertain. We analyzed 1965 males aged 6-80 years in NHANES 2013-2018, relating PFOS, PFOA, PFHxS, and PFNA to estradiol (E2) and sex hormone-binding globulin (SHBG) with survey-weighted linear models; mixture effects were assessed by weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) within age strata. Associations were strongest at ages 6-12: PFOS was associated with higher E2, whereas PFOA and PFNA were associated with lower SHBG, with supportive evidence for PFHxS. Mixture analyses identified PFOS as a main contributor and suggested nonlinear PFOS-E2 increases and monotonic SHBG suppression by PFOA/PFHxS. Juvenile mice received PFOS in drinking water for six weeks; PFOS altered hormones and induced germ-cell injury, consistent with the human window. Our findings suggest that childhood may be a sensitive period for PFAS-related endocrine disruption, warranting child-focused monitoring and mixture-aware risk assessment.