Synergy between deltamethrin and prochloraz in bees: Modeling approach

The metabolic hypothesis proposes that the fungicide prochlorazacts synergistically on deltamethrin by inhibiting oxidative metabolism of deltamethrin. The limits of validity of this hypothesis were tested using a pharmacokinetic box model. Experimental work showed that bee mortalities were higher after 2 h in groups sprayed with deltamethrin at 0.25 g-ha−1 in the presence of prochloraz (25 g-ha−1) than in those sprayed at 1 g-ha−1 with deltamethrin alone. We defined t as the time at which the internal concentration of deltamethrin is the same for both treatments. For the metabolic hypothesis to be consistent with experimental results, t must be less than 2 h. Given t < 2 h, the model was used to study pharmacokinetic parameter values. Published parameter values were inconsistent with simulation results because in all cases t was greater than 2 h. Consequently, the synergy between prochloraz and deltamethrin cannot be explained by the inhibition of oxidative metabolism.