Synergistic Effects of Amitraz and Dinotefuran on Honey Bee Health: Impacts on Survival, Gene Expression, and Hypopharyngeal Gland Morphology.

Honey bees (Apis mellifera) are major pollinators, playing a critical role in global food production, biodiversity, and ecosystem stability. However, their populations are increasingly threatened by multiple interacting stressors, including pesticide exposure. Among these, agricultural insecticides and anti-Varroa acaricides such as dinotefuran and amitraz can persist in hive matrices, resulting in chronic and combined exposure. This study investigates the low lethal (LC10 and LC30) effects of these compounds, individually and in combination, on honey bee survival, immune function, oxidative stress responses, detoxification pathways, and hypopharyngeal gland morphology. Both pesticides negatively affected honey bee health at low lethal concentrations, with dinotefuran showing higher toxicity. Exposure led to the reduced survival, suppression of vitellogenin expression, and dysregulation of genes related to antioxidant defense, immunity, and detoxification. Additionally, high concentrations of dinotefuran and its combination with amitraz impaired hypopharyngeal gland morphology. Notably, co-exposure resulted in synergistic toxic effects, exacerbating physiological damage beyond individual treatments. These findings emphasize the potential risks of combined exposure to agricultural and beekeeping pesticides. A more comprehensive risk assessment and stricter regulations are urgently needed.