Evaluation of novel carbamate insecticides for neurotoxicity to non-target species

• Carbamates exhibit selectivity for Anopheles gambiae acetylcholinesterase (AChE) over human.
• Carbamates were tested on AChE from non-target species and exhibited up to 582-fold selectivity.
• In vivo assay of D. magna confirmed low or acceptable toxicity to aquatic invertebrates.
• Neurotoxic esterase was unaffected by experimental carbamates (up to 1 mM).
• Experimental carbamates possess more favorable safety profiles than commercial carbamates.

Malaria is an urgent world health concern and vector control is one important option for reducing disease prevalence. Increased reports of pyrethroid-resistant mosquito strains have amplified the need for new vector-control chemicals. We compared three commercially available carbamate insecticides (carbofuran, bendiocarb, and propoxur) to eight experimental compounds 1–8 for activity against Anopheles gambiae acetylcholinesterase, as well as enzymes from mammalian, avian, and aquatic species. The experimental compounds (except 7) were less potent than the commercial inhibitors against the mosquito enzyme, but had higher selectivity values (up to near 600-fold, IC50 of non-target species/IC50An. gambiae) because of their low potency for acetylcholinesterases from nontarget species. Neurotoxic esterase assay showed that none of the experimental carbamates (1 mM) displayed NTE inhibition, while bendiocarb did (24% inhibition at 1 mM), although the effect was much less than that of mipafox. In vivo bioassays using Daphnia magna showed that all novel carbamates were of similar killing potency as bendiocarb (24 h LC50 = 611 nM), with the exception of experimental compound 1 (LC50 = 172 nM). Overall, the results suggested that the novel carbamate insecticides 4–8 presented in this study were safer to mammals than the commercial compounds and were promising insecticides for malaria vector control usage on bednets or indoor residual sprays.

Structure of carbamate insecticides having reduced potency against acetylcholinesterases of non-target species compared to commercially available carbamates.Figure optionsDownload as PowerPoint slide