Clinical Masking of Insecticide Toxicity: Pharmacological Antagonism Between Flupyradifurone and Deltamethrin in Honeybees (Apis mellifera)

Introduction: In veterinary apiculture, diagnosing pesticide poisoning is challenging because current toxicological frameworks are based on single-agent acute lethality (LD50), which does not account for pharmacological interactions. Flupyradifurone (FL) and deltamethrin (DM) have overlapping agricultural use, but their combined clinical effects are unknown. This study characterized their acute oral toxicity alone and in combination.

Methods: Caged honeybees (20 per group, 10 replicates) received oral administration of: DM 21.6 mg/L; FL 50 mg/L; FL 100 mg/L; DM+FL50; DM+FL100; or sugar solution (control). Clinical monitoring over 72 hours included survival (Kaplan-Meier), daily food consumption, and abnormal behavior (incoordination, decreased movement, moribundity).

Results: DM alone caused significant mortality vs. controls (p<0.001). FL 50 mg/L allowed 46% survival at day 3. FL 100 mg/L caused 100% mortality by day 2. DM+FL50 significantly improved survival vs. DM alone (p<0.001) and vs. FL50 alone (p<0.001). DM+FL100 significantly improved survival vs. FL100 alone (p<0.001), with bees surviving up to day 3, while no significant improvement was observed vs. DM alone (p>0.05). Food consumption and abnormal behavior confirmed antagonism.

Conclusions: Antagonism between FL and DM can mask toxicity severity, leading to clinical underestimation of pesticide exposure in honeybees. By pharmacological extrapolation, similar antagonistic interactions may occur in livestock species (e.g., sheep, cattle, pigs) exposed to contaminated feed or pastures, potentially concealing subacute or chronic poisoning. From a veterinary clinical perspective, this challenges the assumption that single-agent toxicity data predict real-world outcomes across species. Diagnostic protocols should include multi-residue screening, and risk assessment frameworks must integrate mixture toxicity testing for both pollinators and production animals.