Drosophila as a model in organophosphate toxicology

Organophosphates (OPs) cause acute cholinergic toxicity, oxidative stress, DNA damage, and delayed axonopathy through neuropathy target esterase (NTE) inhibition. Efficient in vivo models capturing this toxicity spectrum are essential for risk assessment and therapeutic discovery. Here, we review Drosophila melanogaster as a versatile platform for OP toxicology across: (1) wild-type assays using dietary and vapour exposures with behavioural endpoints (survival, locomotion, negative geotaxis) and biochemical markers (acetylcholinesterase activity, oxidative stress indices); (2) genotoxicity assessment via the Somatic Mutation and Recombination Test (SMART) and comet assay; and (3) the swiss cheese (sws) mutant model – the Drosophila ortholog of human PNPLA6/NTE – enabling investigation of organophosphate-induced delayed neuropathy (OPIDN) independent of cholinergic effects. Together, these approaches provide hazard characterization and support discovery of protective strategies targeting both cholinergic and non-cholinergic pathways.