Chlorpyrifos and Chlorpyrifos-Oxon: A Widening Spectrum of Toxicity

Chlorpyrifos (CP) remains one of the most globally pervasive organophosphorus pesticides, and its toxicological profile continues to raise substantial public health and environmental concerns. While traditionally characterized by its potent acetylcholinesterase-inhibitory properties, accumulating evidence now shows that chlorpyrifos and its bioactive metabolite, chlorpyrifos-oxon (CPO), exert far broader toxic effects, including the induction of oxidative stress, enhancement of neuroinflammatory processes, and the triggering of persistent epigenetic alterations. In this review, we synthesize current findings to highlight the expanding spectrum of CP-induced toxicity, while also providing a multidisciplinary overview of chlorpyrifos characteristics, including its environmental fate, metabolism, and transformation pathways. The analysis encompasses not only classical neurotoxicity but also disruptions in neurodevelopment, endocrine signaling, gut microbiota composition, hepatic function, musculoskeletal integrity and carcinogenic pathways. By synthesizing results across human, animal, and environmental studies, this review offers a comprehensive overview of CP's multidimensional toxicity and highlights the urgent need for improved biomonitoring, regulatory harmonization, and global strategies to reduce exposure.