Identification and prioritisation of biomarkers of organophosphorus compounds-induced neurotoxicity

Organophosphorus compounds (OPCs), a diverse group of chemicals widely utilised as pesticides and flame retardants, pose significant neurotoxic risks, even during neurodevelopment. While their primary molecular and cellular targets are well characterised, growing evidence suggest additional mechanis...

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Main Authors: Antonio F. Hernández, Marina Lacasaña, Helena Garcia-Cortés, Mariana F. Fernández, Beatriz Gozález-Alzaga
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Environment International
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Online Access:http://www.sciencedirect.com/science/article/pii/S0160412025001977
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author Antonio F. Hernández
Marina Lacasaña
Helena Garcia-Cortés
Mariana F. Fernández
Beatriz Gozález-Alzaga
author_facet Antonio F. Hernández
Marina Lacasaña
Helena Garcia-Cortés
Mariana F. Fernández
Beatriz Gozález-Alzaga
author_sort Antonio F. Hernández
collection DOAJ
description Organophosphorus compounds (OPCs), a diverse group of chemicals widely utilised as pesticides and flame retardants, pose significant neurotoxic risks, even during neurodevelopment. While their primary molecular and cellular targets are well characterised, growing evidence suggest additional mechanisms, particularly in developmental neurotoxicity. Despite extensive research, predictive biomarkers of OPC-induced neurotoxicity beyond acetylcholinesterase remain underexplored. This study conducted a comprehensive review of epidemiological, in vivo, and in vitro evidence to identify and prioritise biomarkers associated with OPC-induced neurotoxicity. Findings highlight the critical roles of non-cholinergic mechanisms, including neuroinflammation, mitochondrial dysfunction, oxidative stress, and epigenetic modifications. Biomarkers were categorised based on their biological function, mechanistic relevance, and feasibility for early, non-invasive detection. Current research efforts focus on validating sensitive and reliable biomarkers capable of predicting and monitoring nervous system damage and severity. Growing attention is being directed toward non-invasive biomarkers that correlate with behavioural, neuropathological, and imaging outcomes. This review addresses two main aspects. The first provides an overview of established and emerging biomarkers for assessing neurotoxicity in the general population and in individuals occupationally exposed to OPC. The second evaluates molecular biomarkers prioritised based on scientific robustness, clinical relevance, and regulatory applicability. A structured ranking of biomarkers across different levels of biological organisation is proposed to enhance mechanistic understanding and improve risk assessment. This study underscores the need for a standardised biomarker framework for neurotoxicity risk assessment and regulatory decision-making. Implementing these biomarkers in biomonitoring for predictive purposes will facilitate early detection and prevention strategies, ultimately mitigating neurotoxic effects in exposed individuals.
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spelling doaj-art-d9778092ab534bd5bdb8f04610d8d2ab2025-08-20T03:18:31ZengElsevierEnvironment International0160-41202025-05-0119910944610.1016/j.envint.2025.109446Identification and prioritisation of biomarkers of organophosphorus compounds-induced neurotoxicityAntonio F. Hernández0Marina Lacasaña1Helena Garcia-Cortés2Mariana F. Fernández3Beatriz Gozález-Alzaga4Department of Legal Medicine and Toxicology, University of Granada School of Medicine, 18016 Granada, Spain; Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), Spain (CIBERESP), Instituto de Salud Carlos III, 28029 Madrid, Spain; Corresponding authors.Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), Spain (CIBERESP), Instituto de Salud Carlos III, 28029 Madrid, Spain; Andalusian School of Public Health (EASP), 18011 Granada, Spain; Andalusian Health and Environment Observatory (OSMAN), Granada, Spain; Corresponding authors.Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; Andalusian School of Public Health (EASP), 18011 Granada, SpainInstituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), Spain (CIBERESP), Instituto de Salud Carlos III, 28029 Madrid, Spain; Department of Radiology and Physical Medicine, School of Medicine, University of Granada 18016 Granada, Spain; Biomedical Research Centre (CIBM), University of Granada 18016 Granada, SpainInstituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), Spain (CIBERESP), Instituto de Salud Carlos III, 28029 Madrid, Spain; Andalusian School of Public Health (EASP), 18011 Granada, SpainOrganophosphorus compounds (OPCs), a diverse group of chemicals widely utilised as pesticides and flame retardants, pose significant neurotoxic risks, even during neurodevelopment. While their primary molecular and cellular targets are well characterised, growing evidence suggest additional mechanisms, particularly in developmental neurotoxicity. Despite extensive research, predictive biomarkers of OPC-induced neurotoxicity beyond acetylcholinesterase remain underexplored. This study conducted a comprehensive review of epidemiological, in vivo, and in vitro evidence to identify and prioritise biomarkers associated with OPC-induced neurotoxicity. Findings highlight the critical roles of non-cholinergic mechanisms, including neuroinflammation, mitochondrial dysfunction, oxidative stress, and epigenetic modifications. Biomarkers were categorised based on their biological function, mechanistic relevance, and feasibility for early, non-invasive detection. Current research efforts focus on validating sensitive and reliable biomarkers capable of predicting and monitoring nervous system damage and severity. Growing attention is being directed toward non-invasive biomarkers that correlate with behavioural, neuropathological, and imaging outcomes. This review addresses two main aspects. The first provides an overview of established and emerging biomarkers for assessing neurotoxicity in the general population and in individuals occupationally exposed to OPC. The second evaluates molecular biomarkers prioritised based on scientific robustness, clinical relevance, and regulatory applicability. A structured ranking of biomarkers across different levels of biological organisation is proposed to enhance mechanistic understanding and improve risk assessment. This study underscores the need for a standardised biomarker framework for neurotoxicity risk assessment and regulatory decision-making. Implementing these biomarkers in biomonitoring for predictive purposes will facilitate early detection and prevention strategies, ultimately mitigating neurotoxic effects in exposed individuals.http://www.sciencedirect.com/science/article/pii/S0160412025001977Organophosphate compoundsPesticidesFlame retardantsEffect biomarkersNeurotoxicityBehavioural endpoints
spellingShingle Antonio F. Hernández
Marina Lacasaña
Helena Garcia-Cortés
Mariana F. Fernández
Beatriz Gozález-Alzaga
Identification and prioritisation of biomarkers of organophosphorus compounds-induced neurotoxicity
Environment International
Organophosphate compounds
Pesticides
Flame retardants
Effect biomarkers
Neurotoxicity
Behavioural endpoints
title Identification and prioritisation of biomarkers of organophosphorus compounds-induced neurotoxicity
title_full Identification and prioritisation of biomarkers of organophosphorus compounds-induced neurotoxicity
title_fullStr Identification and prioritisation of biomarkers of organophosphorus compounds-induced neurotoxicity
title_full_unstemmed Identification and prioritisation of biomarkers of organophosphorus compounds-induced neurotoxicity
title_short Identification and prioritisation of biomarkers of organophosphorus compounds-induced neurotoxicity
title_sort identification and prioritisation of biomarkers of organophosphorus compounds induced neurotoxicity
topic Organophosphate compounds
Pesticides
Flame retardants
Effect biomarkers
Neurotoxicity
Behavioural endpoints
url http://www.sciencedirect.com/science/article/pii/S0160412025001977
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