Abstract
The aim of this work is to propose methods to test mechanism of synergy of toxic agents in bees. A synergy between prochloraz, an imidazole fungicide, and deltamethrin, a pyrethroid insecticide, was demonstrated experimentally. The hypothesis is that prochloraz modifies the penetration or the metabolism of deltamethrin. This hypothesis is tested using a pharmacokinetic box model. A previous experimental work showed that bee instantaneous mortalities were higher, from the time t 1 to the time t 2 after spraying, in groups sprayed with deltamethrin at dose D 0 in the presence of prochloraz (Δ+P) than in those sprayed with deltamethrin alone at a dose α time as high (αΔ). We postulate that accrued mortality is proportional to the cumulated internal deltamethrin (ID 2). ID 2 of treatment (Δ+P) had to be greater than ID 2 of treatment (αΔ) during the period from t 1 to t 2 so that the hypothesis would be consistent with the experimental data. The limit, for which the hypothesis is conceivable, is the ID 2(αΔ) = ID 2(Δ+P ) curve. We study, in particular, the asymptotic behaviour of the limit curve when different parameters of the kinetic model tend to 0 or ∞. These limits allow to verify quickly and easily whether a mechanism is conceivable or not As the limits are calculated with algebraic values, the test can be used for other synergies.
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Chalvet-Monfray, K., Auger, P., Belzunces, L.P. et al. Modelling based method for pharmacokinetic hypotheses test. Acta Biotheor 44, 335–348 (1996). https://doi.org/10.1007/BF00046537
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DOI: https://doi.org/10.1007/BF00046537