Repurposing isoxazoline insecticides to control Varroa destructor populations in honey bee colonies.

BACKGROUND The devastating honey bee (Apis mellifera) pest, Varroa destructor, has developed resistance to commonly used synthetic acaricides, such as amitraz, tau-fluvalinate, and coumaphos. To find new active ingredients that may be useful in reducing V. destructor populations in honey bee colonies, we examined the acute toxicity of isoxazoline insecticides that are toxic to ectoparasites, such as ticks and fleas. RESULTS Here, we evaluated the toxicity of afoxolaner, fluralaner, sarolaner, and lotilaner to V. destructor and honey bees using direct application methods. Fluralaner (median lethal dose (LD50) = 0.07 ng/V. destructor) was the most toxic isoxazoline insecticide and only 2× less toxic than amitraz (0.04 ng/V. destructor), but 25,600× more toxic than coumaphos (1789 ng/V. destructor). Sarolaner (selectivity ratio = 0.3) was much more toxic to honey bees than to V. destructor, while afoxolaner toxicity was equal to mites and bees. Fluralaner and lotilaner were 123× and 2× more toxic to V. destructor than to honey bees. In addition to describing isoxazolines as a putative chemical class to control V. destructor, we tested the potency of fluralaner against the firing frequency of V. destructor central neurons. Exposure to 30 μm fluralaner led to reversal of GABA inhibition with a significant increase of nerve firing when compared to GABA firing rates. CONCLUSION These data suggest that fluralaner represents a potential candidate for V. destructor control in colonies due to its high toxicity to V. destructor and its relatively low toxicity to honey bees. Additionally, methodological details for electrophysiological recordings on V. destructor central nervous system (CNS) firing rates can be used to advance the development of new miticides. © 2025 Society of Chemical Industry.