flupyradifurone and butenolide

Flupyradifurone (FPF), a novel butenolide insecticide binding to nicotinic acetylcholine receptors (nAChRs), has been shown to be less acutely toxic to western honey bees (Apis mellifera) than other insecticides such as neonicotinoids sharing the same target-site. A previous study revealed that this is due to enhanced oxidative metabolism of FPF, mediated by three cytochrome P450 monooxygenases (P450s), including CYP6AQ1. Therefore, we followed a toxicogenomics approach and investigated the potential role of functional CYP6AQ1 orthologs in FPF metabolism from eight different bee species, including stingless bees (Tribe: Meliponini). We conducted a phylogenetic analysis on four stingless bee species, including Frieseomelitta varia, Heterotrigona itama, Melipona quadrifasciata and Tetragonula carbonaria to identify CYP6AQ1-like functional orthologs. Three non-Meliponini, but tropical bee species, i.e., Ammobates syriacus, Euglossa dilemma and Megalopta genalis were analyzed as well. We identified candidate P450s in all (neo)tropical species with greater than 61% and 67% predicted protein sequence identities when compared to A. mellifera CYP6AQ1 and Bombus terrestris CYP6AQ26, respectively. Heterologous expression in High Five insect cells of these functional orthologs revealed a common coumarin substrate profile and a preference for the O-debenzylation of bulkier substrates. Competition assays using the fluorescent probe substrate 7-benzyloxymethoxy-4-trifluoromethylcoumarin (BOMFC) with these enzymes indicated inhibition of BOMFC metabolism by increasing concentrations of FPF. Furthermore, UPLC-MS/MS analysis revealed the capacity of all CYP6AQ1-like orthologs to metabolize FPF by hydroxylation in vitro at various levels, indicating a conserved FPF detoxification potential in different (neo)tropical bee species including Meliponini. This research, employing a toxicogenomics approach, provides important insights into the potential of stingless and other tropical bee species to detoxify FPF, and highlights the significance of investigating the detoxification mechanisms of insecticides in non-Apis bee species by molecular tools to inform risk assessment and conservation efforts.

Topics: Animals; Bees; Chromatography, Liquid; Insecticides; Phylogeny; Tandem Mass Spectrometry

Flupyradifurone, a novel butenolide insecticide, selectively targets insect nicotinic acetylcholine receptors (nAChRs), comparable to structurally different insecticidal chemotypes such as neonicotinoids and sulfoximines. However, flupyradifurone was shown in acute toxicity tests to be several orders of magnitude less toxic to western honey bee (Apis mellifera L.) than many other insecticides targeting insect nAChRs. The underlying reasons for this difference in toxicity remains unknown and were investigated here. Pharmacokinetic studies after contact application of [

Topics: 4-Butyrolactone; Animals; Bees; Cytochrome P-450 Enzyme System; Fungicides, Industrial; Imidazoles; Insecticides; Neonicotinoids; Pyridines; Toxicogenetics; Triazoles

Sublethal exposure to neonicotinoids, a popular class of agricultural pesticides, can lead to behavioral effects that impact the health of pollinators. Therefore, new compounds, such as flupyradifurone (FPF), have recently been developed as 'safer' alternatives. FPF is an excitotoxic nicotinic acetylcholine receptor agonist, similar to neonicotinoids. Given the novelty of FPF, what data exist are focused mostly on assessing the effect of FPF on pollinator mortality. One important avenue for investigation is the potential effect of FPF on the sensitivity of nectar foragers, such as Apis mellifera, to sucrose concentrations. Neonicotinoids can alter this sucrose responsiveness and disrupt foraging. Compounding this effect, neonicotinoid-containing solutions are preferred by A. mellifera over pure sucrose solutions. We therefore conducted four studies, administering FPF under both acute and chronic conditions, and at field-realistic and higher than field-realistic doses, to assess the influence of FPF exposure on sucrose responsiveness and sucrose solutions with FPF in A. mellifera nectar foragers.. We found no evidence that FPF exposure under acute or chronic field-realistic conditions significantly altered sucrose responsiveness, and we did not find that bees exposed to FPF consumed more of the solution. However, at the much higher median lethal dose (48 h), among bees that survived, FPF-exposed foragers responded to significantly lower concentrations of sucrose than controls and responded at significantly higher rates to all concentrations of sucrose than controls.. We found no evidence that FPF alters the sucrose responsiveness of nectar foragers at field-realistic doses during winter or early spring, but caution and further investigation are warranted, particularly on the effects of FPF in conjunction with other stressors. © 2019 Society of Chemical Industry.

Topics: 4-Butyrolactone; Animals; Bees; Insecticides; Neonicotinoids; Pyridines; Sucrose

The cosmopolitan pest Aphis gossypii (Glover) causes considerable economic losses on various crops by its feeding damage and transmitting diseases around the world. Flupyradifurone is a novel butenolide pesticide; its toxicity on A. gossypii parent generation (F0) was estimated following treatment with LC25 concentration for 48 h. The adult longevity and fecundity of the F0 individuals treated by flupyradifurone showed no significant decrease in comparison with the control. Life table method was used to evaluate the sublethal effects on progeny population (F1). Results showed that the development time of the fourth instar and the preadult as well as the total pre-reproductive period were significantly prolonged, while their fecundity was significantly decreased compared with the control. Additionally, the intrinsic rate of increase (r), the finite rate of increase (λ), and the net reproductive rate (R0) of F1 were all significantly lower in the group treated by LC25 than in the control group. These results reveal that the sublethal concentration of flupyradifurone could suppress the population growth of A. gossypii and indicate that this novel insecticide may be as a useful tool in pest management.

Topics: 4-Butyrolactone; Animals; Aphids; Fertility; Insecticides; Pyridines

Neonicotinoid insecticides are environmentally persistent and highly water-soluble, and thus are prone to leaching into surface waters where they may negatively affect non-target aquatic insects. Most of the research to date has focused on imidacloprid, and few data are available regarding the effects of other neonicotinoids or their proposed replacements (butenolide insecticides). The objective of this study was to assess the toxicity of six neonicotinoids (imidacloprid, thiamethoxam, acetamiprid, clothianidin, thiacloprid, and dinotefuran) and one butenolide (flupyradifurone) to Hexagenia spp. (mayfly larvae). Acute (96-h), water-only tests were conducted, and survival and behaviour (number of surviving mayflies inhabiting artificial burrows) were assessed. Acute sublethal tests were also conducted with imidacloprid, acetamiprid, and thiacloprid, and in addition to survival and behaviour, mobility (ability to burrow into sediment) and recovery (survival and growth following 21 d in clean sediment) were measured. Sublethal effects occurred at much lower concentrations than survival: 96-h LC50s ranged from 780 μg/L (acetamiprid) to >10,000 μg/L (dinotefuran), whereas 96-h EC50s ranged from 4.0 μg/L (acetamiprid) to 630 μg/L (thiamethoxam). Flupyradifurone was intermediate in toxicity, with a 96-h LC50 of 2000 μg/L and a 96-h EC50 of 81 μg/L. Behaviour and mobility were impaired significantly and to a similar degree in sublethal exposures to 10 μg/L imidacloprid, acetamiprid, and thiacloprid, and survival and growth following the recovery period were significantly lower in mayflies exposed to 10 μg/L acetamiprid and thiacloprid, respectively. A suite of effects on mayfly swimming behaviour/ability and respiration were also observed, but not quantified, following exposures to imidacloprid, acetamiprid, and thiacloprid at 1 μg/L and higher. Imidacloprid concentrations measured in North American surface waters have been found to meet or exceed those causing toxicity to Hexagenia, indicating that environmental concentrations may adversely affect Hexagenia and similarly sensitive non-target aquatic species.

Topics: 4-Butyrolactone; Animals; Ephemeroptera; Guanidines; Imidazoles; Insecticides; Larva; Neonicotinoids; Nitro Compounds; Oxazines; Pyridines; Thiamethoxam; Thiazines; Thiazoles

Cucurbit yellow stunting disorder virus (CYSDV) is a whitefly-transmitted Crinivirus (Closteroviridae) that impacts melon production in many parts of the world including the USA. It has been responsible for melon crop loss in the southwestern U.S. since 2006 when it was first identified. Control strategies have revolved mainly around chemical control, but research to identify suitable products and approaches to implementing them have lagged. The current study investigated the performance of four systemic insecticides in the field while concurrently tracking CYSDV disease progression after controlled and natural whitefly inoculation of young melon plants. Assessments of virus incidence were made using two different visual observation methods in concert with ELISA analyses of leaf disks samples collected biweekly. Infection rates were consistently lowest in plots treated with the butenolide insecticide flupyradifurone while dinotefuran was second in efficacy measures. Flupyradifurone also held whitefly densities to their lowest numbers relative to the other treatments. Two other insecticides, imidacloprid and cyantraniliprole, exacerbated virus incidence in multiple trials. Further investigation into the anomalous finding of increased virus incidence due to insecticide application is ongoing.

Topics: 4-Butyrolactone; Animals; Crinivirus; Cucurbitaceae; Guanidines; Hemiptera; Insect Vectors; Insecticides; Neonicotinoids; Nitro Compounds; ortho-Aminobenzoates; Plant Diseases; Pyrazoles; Pyridines