Toxicity, mode of action, and synergist potential of flonicamid against mosquitoes

Abstract

The present study focused on the toxicity of the aphid anti-feedant flonicamid and its main metabolite, 4-trifluoromethylnicotinamide (TFNA-AM) to Aedes aegypti and Anopheles gambiae mosquitoes.The compounds were toxic to both species via topical application, resulting in un-coordinated locomotion and leg splaying, with a favorable An. gambiae LD 50value of 35 ng/mg for TFNA-AM, but no significant lethality to Ae. aegypti at 10 μg/female.There was mild cross resistance in the Akron-kdr (Akdr) strain of An. gambiae. Both compounds were non-toxic to intact larvae (LC 50 >300 ppm); however, headless Ae. aegypti larvae displayed spastic paralysis, with PC 50 values of 2-4 ppm, indicating that the cuticle is a significant barrier to penetration. TFNA-AM showed low mammalian toxicity, with an LD 50 of >2000 mg/kg in mice. Electrophysiological experiments showed larval Aedes muscle depolarization and Kv2 channel blocking activity that required near mM concentrations, suggesting that this potassium channel is not the main target for flonicamid nor its metabolite.However, TFNA-AM was a potent blocker of evoked body wall sensory discharge in dipteran larvae, suggesting that some component of the chordotonal organ system may be involved in its toxicity. Finally, flonicamid and TFNA-AM showed about 2-fold synergism of permethrin toxicity against An. gambiae adult females whose mechanism should become more clear once the mode of action of these compounds is better defined.

Characterizing Permethrin and Etofenprox Resistance in Two Common Laboratory Strains of Anopheles gambiae (Diptera: Culicidae)

“…The paralytic effect of the test compounds was examined using a previously described headless larval assay [20,21] that was adapted for An. gambiae.…”

Pharmacological Inhibition of Inward Rectifier Potassium Channels Induces Lethality in Larval Aedes aegypti

“…gambiae [13] and adult soybean aphids, Aphis glycines [20]. The relatively slow time course (i.e., >24 h) for barium and VU041 to become toxic against larvae may be attributed to: (1) low permeability of the cuticle and/or gut epithelium to these molecules, thereby limiting their access to the hemolymph, as was observed previously for flonicamid [27]; and/or (2) a chronic mechanism of toxicity, such as disruption of osmoregulation.…”

“…aegypti and An. gambiae , albeit the weak cuticular penetration of this compound likely limited its efficacy [27].…”

Fatty Acid and Related Potassium Kv2 Channel Blockers: Toxicity and Physiological Actions on Mosquitoes

“…In the present study, FA co-applied with permethrin yielded differential toxicity rates (Table 3): only 5-HDC slightly decreased the LD 50 value of permethrin, while DAUDA and decanoic acid had no visible effect on mortality. Permethrin synergistic action on mosquitoes has been shown with different compounds such as propoxur or flonicamid, acting on different targets than Kv channels [26,39]. Moreover, piperonyl butoxide (PBO), a known synergistic agent to many pesticide compounds [40,41], has also been tested in co-application with decanoic acid or 5-HDC (see Supplementary Figure S1 and Table S1).…”

“…The synergistic action of pyrethroids with organophosphates have been documented [22,23] and tested on insects [24]. Synergistic action of propoxur [25] and flonicamid [26] with permethrin has been demonstrated on mosquitoes, so we further examined the utility of K + channel blockers as permethrin synergists for control of disease-vectoring mosquitoes. In light of these results, we also discuss the use of fatty acids as biochemicals in the scope of integrated pest management, to better fit the legislative framework of pesticides regulation [27].…”