Gambardella_2026_Front.Cell.Death_5_1680195

Pesticides are an emerging category of contaminants employed in agriculture or for domestic use. Among them, anti-cholinesterase insecticides are the most extensively applied. These are neurotoxic compounds released into the environment in an estimated millions of tons per year, posing serious risks to both environmental and human health. This review examines the current literature on hazard identification and the assessment of two major classes of neurotoxic compoundsorganophosphates (OPs) and carbamates (CBs)in relation to human and environmental health. We report the harmful effects of OPs and CBs on humans and present bioethical models as alternatives to vertebrates in toxicological testing. We describe the most utilized bioassays, employing a range of experimental models (cells, monolayer cultures, spheroids, and whole organisms) exposed to different doses of OPs and CBs, to identify and quantify the most sensitive biological responses (endpoints and biomarkers). This novel approach aims to improve predictive capacity and strengthen the risk assessment of human and environmental health. In conclusion, in vitro or non-mammalian models are promising alternatives for assessing human health risks caused by OPs and CBs, in line with the ""Replacement, Reduction, and Refinement"" (3R) principle.