The effects of prenatal alkylphenols exposure on offspring neurodevelopment: evidence-based risk assessment with the TRAEC strategy

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% 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) with 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, incorporating reliability, weight of concentration, risk intensity, and correlation. Risk rankings for the nine APs evaluated were as follows: 4-P-NP > 4-N-NP > P-NP > 4-OP > 4-T-OP > NP > OP > 4-N-OP > 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 - ToxRTool, SciRAP, OHAT, and IRIS - highlighting its methodological robustness. This study successfully applies the TRAEC framework, advancing the understanding of neurodevelopmental risks following prenatal alkylphenol exposure.