The effects of prenatal alkylphenol exposure on offspring neurodevelopment: an evidence-based risk assessment using the TRAEC strategy

Abstract

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.

Keywords

Alkylphenols / neurodevelopmental disorders / risk assessment / TRAEC strategy

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