The neurodevelopmental effects of early pregnancy exposure to alkylphenols (APs) have been extensively studied, yet findings remain inconsistent. To address these discrepancies, 28 published studies were integrated with an original epidemiological dataset, and the Targeted Risk Assessment of Environmental Chemicals (TRAEC) strategy (version 1.1) was employed. Analysis of the primary early pregnancy cohort data revealed consistent inverse associations between maternal exposure to nonylphenol (NP) [β = -3.032; 95% confidence interval (95%CI): -6.059, -0.005], 4-nonyl-nonylphenol (4-N-NP) (β = -4.280; 95%CI: -7.402, -1.159), and 4-tert-octylphenol (4-T-OP) (β = -5.835; 95%CI: -10.879, -0.792) and children’s Ages and Stages Questionnaire (ASQ) scores, as indicated by generalized linear models (GLMs). These findings suggest that early pregnancy exposure to APs may disrupt neurodevelopmental trajectories in children, with sex-specific vulnerabilities. To provide a thorough assessment throughout gestation, the neurodevelopmental risks of prenatal AP exposure were systematically evaluated by incorporating reliability, weight of concentration, risk intensity, and correlation. Risk rankings for the nine APs evaluated were as follows: 4-para-nonylphenol (4-P-NP) > 4-N-NP > para-nonylphenol (P-NP) > 4-octylphenol (4-OP) > 4-T-OP > nonylphenol (NP) > octylphenol (OP) > 4-nonyl-octylphenol (4-N-OP) > 4-nonylphenol (4-NP). The final comprehensive risk score of 5.91 indicated a moderate level of neurotoxicity risk. Additionally, the TRAEC assessment demonstrated strong alignment with four established frameworks - Toxicological data reliability assessment tool (ToxRTool), Science in Risk Assessment and Policy (SciRAP), Office of Health Assessment and Translation (OHAT), and Integrated Risk Information System (IRIS) - highlighting its methodological robustness. This study successfully applies the TRAEC framework, advancing the understanding of neurodevelopmental risks following prenatal AP exposure.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has been on the rise, with nearly one-quarter of the world’s population currently affected by this condition. Per- and polyfluoroalkyl substances (PFAS) have been suggested as emerging and potentially modifiable environmental risk factors for NAFLD. However, relevant epidemiological evidence remains limited. In the present study, 5,348 adult participants were enrolled from the China National Human Biomonitoring study. The fatty liver index (FLI) was computed using waist circumference, body mass index, triglycerides and γ-glutamyltransferase. NAFLD was defined as an FLI value exceeding 30. To explore the associations of PFAS with FLI and NAFLD, weighted multiple linear regression and logistic regression analyses were performed. Weighted quantile sum regression was applied to assess the joint effects of PFAS mixtures on FLI. The weighted prevalence of NAFLD among study participants was 41.8%. Multiple PFAS congeners were positively associated with FLI. PFAS concentrations were categorized into four equal quartiles from the lowest to the highest level. When comparing the highest quartile (Q4) group with the lowest quartile (Q1) group, the adjusted regression coefficients β [95% confidence interval (CI)] for FLI were as follows: perfluorooctanoic acid (PFOA) 3.63 (1.37-5.89), perfluorooctane sulfonic acid 3.11 (0.87-5.35), perfluorononanoic acid 4.20 (1.82-6.59), perfluorohexane sulfonic acid (PFHxS) 3.62 (0.92-6.32), perfluoroheptane sulfonic acid 3.78 (1.31-6.25) and 6:2 chlorinated polyfluoropolyether sulfonic acid 3.65 (1.02-6.29). PFHxS was positively associated with NAFLD. When comparing Q4 group with Q1 group, the adjusted odds ratio (95%CI) was 1.61 (1.04-2.50). Furthermore, fish consumption appeared to attenuate the adverse effects of PFAS on NAFLD. Exposure to PFAS mixtures was positively associated with FLI, with PFOA and PFHxS identified as the major contributing compounds. These findings support that PFAS may act as an emerging and potentially modifiable environmental risk factor for NAFLD, providing new evidence for the environmental determinants of NAFLD.