sulfoxaflor and flupyradifurone

Lethal and sublethal effects of pesticides on nontarget organisms are one of the causes of the current decline of many insect species. However, research in the past decades has focused primarily on pollinators, although other beneficial nontarget organisms such as parasitic wasps may also be affected. We studied the sublethal effects of the four insecticides acetamiprid, dimethoate, flupyradifurone, and sulfoxaflor on pheromone-mediated sexual communication and olfactory host finding of the parasitic wasp Nasonia vitripennis. All agents target cholinergic neurons, which are involved in the processing of chemical information by insects. We applied insecticide doses topically and tested the response of treated wasps to sex pheromones and host-associated chemical cues. In addition, we investigated the mating rate of insecticide-treated wasps. The pheromone response of females surviving insecticide treatment was disrupted by acetamiprid (≥0.63 ng), dimethoate (≥0.105 ng), and flupyradifurone (≥21 ng), whereas sulfoxaflor had no significant effects at the tested doses. Olfactory host finding was affected by all insecticides (acetamiprid ≥1.05 ng, dimethoate ≥0.105 ng, flupyradifurone ≥5.25 ng, sulfoxaflor ≥0.52 ng). Remarkably, females treated with ≥0.21 ng dimethoate even avoided host odor. The mating rate of treated N. vitripennis couples was decreased by acetamiprid (6.3 ng), flupyradifurone (≥2.63 ng), and sulfoxaflor (2.63 ng), whereas dimethoate showed only minor effects. Finally, we determined the amount of artificial nectar consumed by N. vitripennis females within 48 h. Considering this amount (∼2 µL) and the maximum concentrations of the insecticides reported in nectar, tested doses can be considered field-realistic. Our results suggest that exposure of parasitic wasps to field-realistic doses of insecticides targeting the cholinergic system reduces their effectiveness as natural enemies by impairing the olfactory sense. Environ Toxicol Chem 2023;42:2400-2411. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Topics: Animals; Cholinergic Neurons; Dimethoate; Female; Insecticides; Plant Nectar; Sex Attractants; Wasps

The development of novel and safe insecticides remains an important need for a growing world population to protect crops and animal and human health. New chemotypes modulating the insect nicotinic acetylcholine receptors have been recently brought to the agricultural market, yet with limited understanding of their molecular interactions at their target receptor. Herein, we disclose the first crystal structures of these insecticides, namely, sulfoxaflor, flupyradifurone, triflumezopyrim, flupyrimin, and the experimental compound, dicloromezotiaz, in a double-mutated acetylcholine-binding protein which mimics the insect-ion-channel orthosteric site. Enabled by these findings, we discovered novel pharmacophores with a related mode of action, and we describe herein their design, synthesis, and biological evaluation.

Topics: 4-Butyrolactone; Animals; Binding Sites; Coleoptera; Crystallography, X-Ray; Drug Design; Humans; Insect Control; Insect Proteins; Insecticides; Molecular Conformation; Molecular Dynamics Simulation; Mutagenesis, Site-Directed; Pyridines; Pyrimidinones; Receptors, Nicotinic; Sulfur Compounds

The gut microbiome plays an important role in bee health and disease. But it can be disrupted by pesticides and in-hive chemicals, putting honey bee health in danger. We used a controlled and fully crossed laboratory experimental design to test the effects of a 10-day period of chronic exposure to field-realistic sublethal concentrations of two nicotinic acetylcholine receptor agonist insecticides (nACHRs), namely flupyradifurone (FPF) and sulfoxaflor (Sulf), and a fungicide, azoxystrobin (Azoxy), individually and in combination, on the survival of individual honey bee workers and the composition of their gut microbiota (fungal and bacterial diversity). Metabarcoding was used to examine the gut microbiota on days 0, 5, and 10 of pesticide exposure to determine how the microbial response varies over time; to do so, the fungal ITS2 fragment and the V4 region of the bacterial 16S rRNA were targeted. We found that FPF has a negative impact on honey bee survival, but interactive (additive or synergistic) effects between either insecticide and the fungicide on honey bee survival were not statistically significant. Pesticide treatments significantly impacted the microbial community composition. The fungicide Azoxy substantially reduced the Shannon diversity of fungi after chronic exposure for 10 days. The relative abundance of the top 10 genera of the bee gut microbiota was also differentially affected by the fungicide, insecticides, and fungicide-insecticide combinations. Gut microbiota dysbiosis was associated with an increase in the relative abundance of opportunistic pathogens such as Serratia spp. (e.g. S. marcescens), which can have devastating consequences for host health such as increased susceptibility to infection and reduced lifespan. Our findings raise concerns about the long-term impact of novel nACHR insecticides, particularly FPF, on pollinator health and recommend a novel methodology for a refined risk assessment that includes the potential effects of agrochemicals on the gut microbiome of bees.

Topics: 4-Butyrolactone; Animals; Bees; Fungicides, Industrial; Gastrointestinal Microbiome; Insecticides; Pesticides; Pyridines; Pyrimidines; Receptors, Nicotinic; RNA, Ribosomal, 16S; Serratia marcescens; Strobilurins; Sulfur Compounds

The decline of insect pollinators threatens global food security. A major potential cause of decline is considered to be the interaction between environmental stressors, particularly between exposure to pesticides and pathogens. To explore pesticide-pathogen interactions in an important pollinator insect, the honey bee, we used two new nicotinic acetylcholine receptor agonist insecticides (nACHRs), flupyradifurone (FPF) and sulfoxaflor (SULF), at sublethal and field-realistic doses in a fully crossed experimental design with three common viral honey bee pathogens, Black queen cell virus (BQCV) and Deformed wing virus (DWV) genotypes A and B. Through laboratory experiments in which treatments were administered singly or in combination to individual insects, we recorded harmful effects of FPF and pathogens on honey bee survival and immune gene expression. Though we found no evidence of synergistic interactions among stressors on either honey bee survival or viral load, the combined treatment SULF and DWV-B led to a synergistic upregulation of dicer-like gene expression. We conclude that common viral pathogens pose a major threat to honey bees, while co-exposure to these novel nACHR insecticides does not significantly exacerbate viral impacts on host survival in the laboratory.

Topics: 4-Butyrolactone; Animals; Bees; Immunocompetence; Insecticides; Pyridines; RNA Viruses; Sulfur Compounds

Pesticide exposures can have detrimental impacts on bee pollinators, ranging from immediate mortality to sub-lethal impacts. Flupyradifurone is the active ingredient in Sivanto™ and sulfoxaflor is the active ingredient in Transform®. They are both relatively new insecticides developed with an intent to reduce negative effects on bees, when applied to bee-attractive crops. With the growing concern regarding pollinator health and pollinator declines, it is important to have a better understanding of any potential negative impacts, especially sub-lethal, of these pesticides on bees. This study reports novel findings regarding physiological stress experienced by bees exposed to field application rates of these two insecticides via a Potter Tower sprayer. Two contact exposure experiments were conducted-a shorter 6-hour study and a longer 10-day study. Honey bee mortality, sugar syrup and water consumption, and physiological responses (oxidative stress and apoptotic protein assays) were assessed in bees exposed to Sivanto™ and Transform®, and compared to bees in control group. For the longer, 10-day contact exposure experiment, only the Sivanto™ group was compared to the control group, as high mortality recorded in the sulfoxaflor treatment group during the shorter contact exposure experiment, made the latter group unfeasible to test in the longer 10-days experiment. In both the studies, sugar syrup and water consumptions were significantly different between treatment groups and controls. The highest mortality was observed in Transform® exposed bees, followed by the Sivanto™ exposed bees. Estimates of reactive oxygen/nitrogen species indicated significantly elevated oxidative stress in both pesticide treatment groups, when compared to controls. Caspase-3 protein assays, an indicator of onset of apoptosis, was also significantly higher in the pesticide treatment groups. These differences were largely driven by post exposure duration, indicating sub-lethal impacts. Further, our findings also emphasize the need to revisit contact exposure impacts of Sivanto™, given the sub-lethal impacts and mortality observed in our long-term (10-day) contact exposure experiment.

Topics: 4-Butyrolactone; Animals; Bees; Caspase 3; Cell Survival; Insect Proteins; Oxidative Stress; Pesticides; Pollination; Pyridines; Sulfur Compounds; Time Factors

The impact of increasing resistance of mosquitoes to conventional pesticides has led to investigate various unique tools and pest control strategies. Herein, we assessed the potency of flupyradifurone, a novel pesticide, on fourth instar larvae of Culex quinquefasciatus Say. Further, we evaluated the synergistic action of piperonyl butoxide (PBO) and the octopamine receptor agonists (OR agonists) chlordimeform (CDM) and amitraz (AMZ) on the toxicity of flupyradifurone in comparison with sulfoxaflor and nitenpyram to increase their toxicity on Cx. quinquefasciatus. Results demonstrated that flupyradifurone was the most potent pesticide followed by sulfoxaflor and nitenpyram. Further, the synergetic effect of PBO, CDM, and AMZ was significant for all selected pesticides especially flupyradifurone. However, AMZ had the most significant effect in combination with the selected pesticides followed by CDM and PBO. The toxicity of the pesticides was time-dependent and increased over time from 24, 48, to 72 h of exposure in all experiments. The results indicate that flupyradifurone is a promising component in future mosquito control programs.

Topics: 4-Butyrolactone; Animals; Chlorphenamidine; Culex; Insect Proteins; Insecticides; Larva; Mosquito Control; Neonicotinoids; Piperonyl Butoxide; Pyridines; Receptors, Biogenic Amine; Sulfur Compounds; Toluidines

Systemic insecticides, such as neonicotinoids, are a major contributor towards beneficial insect declines. This has led to bans and restrictions on neonicotinoid use globally, most noticeably in the European Union, where four commonly used neonicotinoids (imidacloprid, thiamethoxam, clothianidin and thiacloprid) are banned from outside agricultural use. While this might seem like a victory for conservation, restrictions on neonicotinoid use will only benefit insect populations if newly emerging insecticides do not have similar negative impacts on beneficial insects. Flupyradifurone and sulfoxaflor are two novel insecticides that have been registered for use globally, including within the European Union. These novel insecticides differ in their chemical class, but share the same mode of action as neonicotinoids, raising the question as to whether they have similar sub-lethal impacts on beneficial insects. Here, we conducted a systematic literature search of the potential sub-lethal impacts of these novel insecticides on beneficial insects, quantifying these effects with a meta-analysis. We demonstrate that both flupyradifurone and sulfoxaflor have significant sub-lethal impacts on beneficial insects at field-realistic levels of exposure. These results confirm that bans on neonicotinoid use will only protect beneficial insects if paired with significant changes to the agrochemical regulatory process. A failure to modify the regulatory process will result in a continued decline of beneficial insects and the ecosystem services on which global food production relies.

Topics: 4-Butyrolactone; Animals; Ecosystem; Guanidines; Insecta; Insecticides; Neonicotinoids; Nitro Compounds; Pyridines; Sulfur Compounds; Thiamethoxam; Thiazines; Thiazoles

The use of foliar insecticide sprays at low temperatures may result in decreased efficacy in grain sorghum, Sorghum bicolor L. Moench, for control of sugarcane aphid, Melanaphis sacchari (Zehntner). Sulfoxaflor and flupyradifurone were evaluated to determine the impact of temperature on their efficacy against sugarcane aphid in grain sorghum. Sorghum was treated at the soft dough growth stage with sulfoxaflor and flupyradifurone, as well as an untreated check. Leaf discs were pulled at various intervals from 0 to 10 d after treatment, placed in water agar plates, infested with aphids, placed in growth chambers at 15.5°C or 29.4°C, and evaluated 48 h after each interval. In 2015, both insecticides resulted in similar levels of sugarcane aphid mortality and efficacy decreased at a similar rate at 15.5°C. At 29.0°C, flupyradifurone resulted in greater mortality of sugarcane aphid than sulfoxaflor as length of time after treatment increased, suggesting that it provides longer residual control than sulfoxaflor. In 2016, both insecticides provided poor control of sugarcane aphid at 15.5°C for all time intervals. At 29.0°C, flupyradifurone provided overall better control than sulfoxaflor. These data suggest that lower temperatures can reduce the efficacy of both sulfoxaflor and flupyradifurone. In addition, flupyradifurone appeared to provide longer residual control and overall better control of sugarcane aphid than sulfoxaflor. If lower temperatures occur when sugarcane aphid populations exceed current thresholds, weather forecast should be considered in pest management decision-making process.

Topics: 4-Butyrolactone; Animals; Aphids; Insecticides; Pyridines; Sorghum; Sulfur Compounds; Temperature

Sulfoxaflor is the first commercially available sulfoximine insecticide, which exhibits highly efficacy against many sap-feeding insect pests and has been applied as an alternative insecticide against cotton aphid in China. This study was conducted to investigate the risk of resistance development, the cross-resistance pattern and the potential resistance mechanisms of sulfoxaflor in Aphis gossypii. A colony (SulR strain) of A. gossypii with 245-fold resistance, originated from Xinjiang field population, was established by continuous selection using sulfoxaflor. The SulR strain has developed cross-resistance to imidacloprid (80.8-fold), acetamiprid (19.3-fold), thiamethoxam (10.0-fold), and flupyradifurone (107.5-fold), while no cross-resistance was detected to malathion, omethoate, bifenthrin, methomyl, and carbosulfan. Piperonyl butoxide and S, S, S-tributyl phosphorotrithioate could significantly increase the toxicity of sulfoxaflor to the SulR strain by 5.99- and 4.18-fold, respectively, whereas no synergistic effect with diethyl maleate was observed. The activities of P450s and carboxylesterase were significantly higher in the SulR strain than that in the SS strain. Further gene expression determination demonstrated that nine P450 genes were significantly increased in SulR strain and suppression the expression of CYP6CY13 and CYP6CY19 by RNAi significantly increased the susceptibility of SulR adult aphids to sulfoxaflor. These results demonstrated that the enhancing detoxification by cytochrome P450 monooxygenase may be involved in A.gossypii resistance to sulfoxaflor.

Topics: 4-Butyrolactone; Animals; Aphids; Cytochrome P-450 Enzyme System; Insecticide Resistance; Insecticides; Neonicotinoids; Nitro Compounds; Pyrethrins; Pyridines; Sulfur Compounds

Flupyradifurone and sulfoxaflor present novel insecticide chemistries with particular efficacy against aphids, and the recent emergence of sugarcane aphid, Melanaphis sacchari (Zehntner), as a pest of sorghum in the United States has resulted in their widespread use. We examined their toxicity to Hippodamia convergens Guerin-Meneville, an important aphid biocontrol agent. We exposed beetles to topical applications of the field rate (FR) of these insecticides, fed them contaminated food (eggs of Ephestia kuehniella Zeller), and gave first-instar larvae 24-h exposures to leaf residues. More than half of fourth-instar larvae receiving topical applications of sulfoxaflor at FR survived, whereas flupyradifurone at 0.1× FR caused 90% mortality. Adults survived topical treatments better than larvae and without measurable mortality, except flupyradifurone at FR, which killed more than 80% of beetles. Survivors of all treatments had fertility similar to controls, whether treated as larvae or adults. Ingestion of contaminated food caused significant mortality in all treatments (15-40% for adults and 55-85% for larvae), with no significant differences between insecticides at FR. Leaf residues of sulfoxaflor at 1.0 and 2.0× FR caused approximately 60 and 80% mortality of first instars, respectively, whereas flupyradifurone at 0.1 and 1.0× FR caused > 90% mortality. Although sulfoxaflor was less toxic to H. convergens than flupyradifurone, the tested FR of flupyradifurone has now been reduced by half. We conclude that neither insecticide appears as toxic as other nicotinic acetylcholine receptor agonists, and that both materials are compatible with integrated pest management programs for M. sacchari.

Topics: 4-Butyrolactone; Animals; Coleoptera; Female; Insect Control; Insecticides; Larva; Pest Control, Biological; Predatory Behavior; Pyridines; Sulfur Compounds