RESUMEN
As resistance to the limited number of insecticides available for medical and veterinary pests becomes more widespread, there is an urgent need for new insecticides and synergists on the market. To address this need, we conducted a study to assess the toxicity of three monoterpenoids-carvone, menthone, and fenchone-in comparison to permethrin and methomyl against adults of two common pests: the yellow fever mosquito (Aedes aegypti) and the house fly (Musca domestica). We also examined the potential for these monoterpenoids to enhance the effectiveness of permethrin and methomyl when used together. Finally, we evaluated the ability of each monoterpenoid to inhibit acetylcholinesterase, comparing them to methomyl. While all three monoterpenoids performed relatively poorly as topical insecticides (LD50 > 4000 ng/mg on M. domestica; >6000 ng/mg on Ae. aegypti), they synergized both permethrin and methomyl as well as or better than piperonyl butoxide (PBO). Carvone and menthone yielded synergistic co-toxicity factors (23 and 29, respectively), which were each higher than PBO at 24 h. Currently, the mechanism of action is unknown. During preliminary testing, symptoms of acetylcholinesterase inhibition were identified, prompting further testing. Acetylcholinesterase inhibition did not appear to explain the toxic or synergistic effects of the three monoterpenoids, with IC50 values greater than 1 mM for all, compared to the 2.5 and 1.7 µM for methomyl on Aedes aegypti and Musca domestica, respectively. This study provides valuable monoterpenoid toxicity and synergism data on two pestiferous insects and highlights the potential for these chemistries in future pest control formulations.
Asunto(s)
Aedes , Moscas Domésticas , Insecticidas , Muscidae , Fiebre Amarilla , Animales , Insecticidas/farmacología , Permetrina/farmacología , Acetilcolinesterasa/farmacología , Metomil , Monoterpenos/farmacologíaRESUMEN
House flies, Musca domestica (L), are the mechanical vector of >100 human and animal pathogens, including those that are antibiotic-resistant. Given that house flies are associated closely with human and livestock activity, they present medical and veterinary health concerns. Although there are numerous strategies for control of house fly populations, chemical control has been favored in many facilities. Products with pyrethroid active ingredients have been used predominantly for >35 years in space sprays. As a result, strong selection for pyrethroid resistance has led to reduced control of many populations. Reliance on a limited number of insecticides for decades has created fly control problems necessitating the discovery and formulation of new control chemistries. Fluralaner is a relatively new insecticide and acaricide (first reported in 2010), belonging to the isoxazoline class. These insecticides target the glutamate- and gamma-aminobutyric acid-gated (GABA) chloride channels, which is a different mode of action from other insecticides used against house flies. Although is it not currently registered for house fly control in the United States, previous work has shown that fluralaner is highly toxic to house flies and that there was limited cross-resistance found in laboratory strains having high levels of resistance to other insecticides. Herein, we characterized the time and age dependency of fluralaner toxicity, detected cross-resistance in populations from across the United States, and selected a highly resistant (>11,000-fold) house fly strain. We found that the fluralaner LD50 of 18-24 h old flies was 2-fold higher than for 5-6 d old flies. This appears to be due to more rapid penetration of fluralaner into the 5-6 d old flies. Fluralaner resistance was inherited as an intermediate to incompletely dominant trait and was mapped to chromosomes 5 and 3. Resistance could be suppressed to 7-fold with piperonyl butoxide, suggesting that cytochrome P450 (CYP)-mediated detoxification was a major mechanism of resistance. Decreased penetration was also demonstrated as a mechanism of resistance. The utility of fluralaner for house fly control is discussed.