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 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.