Intracellular calcium handling dysfunction contributes to behavioural deficits leading to mortality of honey bees after acute contact exposure to the insecticide cyantraniliprole.

Synthetic insecticides are recognized as a major factor contributing to the global decline in insect abundance and diversity. Within this context, anthranilic diamides have gained increasing market share in Europe since 2018. We investigated the second-generation diamide cyantraniliprole, which induces aberrant cytoplasmic calcium release in honeybee skeletal muscle cells. In vivo assays demonstrated that acute contact toxicity varied with exposure site, being more severe when applied to the abdomen, antennae, or ventral thorax compared with the dorsal thorax. Following thoracic exposure to sublethal doses, continuous 21-h monitoring revealed a dose-dependent alteration of behavior, with a reduction in locomotor activity, including maximal velocity and total distance traveled. Notably, at the lowest concentration, antennal exposure elicited stronger behavioral impairments, indicating potential disruption of sensory processing and environmental cue perception. Importantly, cyantraniliprole and its parent compound, chlorantraniliprole, also triggered anarchic calcium mobilization in mammalian skeletal muscle fibers, highlighting potential cross-taxa effects. These results strengthen previous evidence of diamides toxicity in bee cardiomyocytes and neurons and emphasize significant gaps in current risk assessment frameworks. Collectively, our findings indicate that anthranilic diamides represent not only an ecological threat to pollinators but also raise concerns for mammalian health, warranting more stringent evaluation of this insecticide class.