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1.
Chem Biodivers ; : e202402098, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39316748

RESUMO

The exponential rise in pesticide resistance to conventional chemical pesticides is another major factor driving the development of novel insecticidal active agents. One approach to solving this problem is to investigate novel classes and environmentally safe insecticidal chemicals with a variety of modes of action. Among these techniques is the creation of novel tebufenozide derivatives. Tebufenozide belongs to the insect growth regulator class of insecticides and is regarded as one of the safest chemical insecticides ever. The toxicological and biochemical efficiency of each analog was assessed against the Spodoptera littoralis pest in both its second and fourth instar larvae. The bioassay results show that compound 7 was the most effective insecticidal agent, with LC50 values of 10.6.5 and 18.7 mg/L against S. littoralis larvae in their second and fourth instar larvae, respectively. Finally, it was shown how treatment with the LC50 of the examined substances affected the activity of many enzymes involved in the cuticle production of S. littoralis larvae in their fourth instar. From this study, it was concluded that Acyl hydrazide are helpful for the management of S. littoralis and will be an effective replacement for other synthetic insecticides.

2.
Ecol Appl ; 33(6): e2890, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37212374

RESUMO

Outbreaks of the spongy moth Lymantria dispar can have devastating impacts on forest resources and ecosystems. Lepidoptera-specific insecticides, such as Bacillus thuringiensis var. kurstaki (BTK) and tebufenozide, are often deployed to prevent heavy defoliation of the forest canopy. While it has been suggested that using BTK poses less risk to non-target Lepidoptera than leaving an outbreak untreated, in situ testing of this assumption has been impeded by methodological challenges. The trade-offs between insecticide use and outbreaks have yet to be addressed for tebufenozide, which is believed to have stronger side effects than BTK. We investigated the short-term trade-offs between tebufenozide treatments and no-action strategies for the non-target herbivore community in forest canopies. Over 3 years, Lepidoptera and Symphyta larvae were sampled by canopy fogging in 48 oak stands in southeast Germany during and after a spongy moth outbreak. Half of the sites were treated with tebufenozide and changes in canopy cover were monitored. We contrasted the impacts of tebufenozide and defoliator outbreaks on the abundance, diversity, and functional structure of chewing herbivore communities. Tebufenozide treatments strongly reduced Lepidoptera up to 6 weeks after spraying. Populations gradually converged back to control levels after 2 years. Shelter-building species dominated caterpillar assemblages in treated plots in the post-spray weeks, while flight-dimorphic species were slow to recover and remained underrepresented in treated stands 2 years post-treatment. Spongy moth outbreaks had minor effects on leaf chewer communities. Summer Lepidoptera decreased only when severe defoliation occurred, whereas Symphyta declined 1 year after defoliation. Polyphagous species with only partial host plant overlap with the spongy moth were absent from heavily defoliated sites, suggesting greater sensitivity of generalists to defoliation-induced plant responses. These results demonstrate that both tebufenozide treatments and spongy moth outbreaks alter canopy herbivore communities. Tebufenozide had a stronger and longer lasting impact, but it was restricted to Lepidoptera, whereas the outbreak affected both Lepidoptera and Symphyta. These results are tied to the fact that only half of the outbreak sites experienced severe defoliation. This highlights the limited accuracy of current defoliation forecast methods, which are used as the basis for the decision to spray insecticides.


Assuntos
Bacillus thuringiensis , Inseticidas , Mariposas , Animais , Ecossistema
3.
Ecotoxicology ; 31(8): 1231-1240, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36083423

RESUMO

The use of insecticides to control undesirable pest species in forestry has undergone a shift from broad spectrum to narrow spectrum insecticides to reduce the risk of effects on non-target species. However, there is still risk of direct effects on non-target species as some insecticides function as hormone mimics, or through indirect pathways as the insecticide is broken down in the environment. Tebufenozide, an ecdysone hormone mimic, is the active ingredient in insecticides used in a variety of large scale pest control programs. An oft cited reason for the safety of Tebufenozide is that it is rapidly broken down in the environment by microbes. We investigated the potential non-target effects of two Tebufenozide formulations used in Canada, Mimic 240LV and Limit 240, on aquatic communities using an outdoor mesocosm experiment. We focus on direct effects on amphibian larvae (wood frog, Rana sylvaticus), zooplankton communities, and effects on biofilm and phytoplanktonic microbial communities that could arise from either direct toxicity, or from breaking down the insecticide as a nutrient and/or carbon source. There was limited evidence for direct effects on amphibian larvae or zooplankton communities. There were small but non-significant shifts in biofilm microbial communities responsible for nutrient cycling. Beta diversity in the plankton community was slightly higher among tanks treated with insecticide indicating a community dispersion/disbiosis effect. Overall, we found limited evidence of negative effects, however, subtle changes to microbial communities did occur and could indicate changes to ecosystem function.


Assuntos
Inseticidas , Animais , Carbono , Ecdisona/farmacologia , Ecossistema , Hidrazinas , Inseticidas/farmacologia , Larva , Zooplâncton
4.
Bioorg Med Chem ; 28(9): 115429, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32201191

RESUMO

Cytochrome P450 (CYP) enzymes constitute a superfamily of heme-containing monooxygenases. CYPs are involved in the metabolism of many chemicals such as drugs and agrochemicals. Therefore, examining the metabolic reactions by each CYP isoform is important to elucidate their substrate recognition mechanisms. The clarification of these mechanisms may be useful not only for the development of new drugs and agrochemicals, but also for risk assessment of chemicals. In our previous study, we identified the metabolites of tebufenozide, an insect growth regulator, formed by two human CYP isoforms: CYP3A4 and CYP2C19. The accessibility of each site of tebufenozide to the reaction center of CYP enzymes and the susceptibility of each hydrogen atom for metabolism by CYP enzymes were evaluated by a docking simulation and hydrogen atom abstraction energy estimation at the density functional theory level, respectively. In this study, the same in silico prediction method was applied to the metabolites of tebufenozide derivatives by major human CYPs (CYP1A2, 2C9, 2C19, 2D6, and 3A4). In addition, the production rate of the metabolites by CYP3A4 was quantitively analyzed by frequency based on docking simulation and hydrogen atom abstraction energy using the classical QSAR approach. Then, the obtained QSAR model was applied to predict the sites of metabolism and the metabolite production order by each CYP isoform.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Hidrazinas/metabolismo , Simulação de Acoplamento Molecular , Teoria da Densidade Funcional , Humanos , Hidrazinas/química , Isoenzimas/metabolismo , Estrutura Molecular
5.
Ecotoxicol Environ Saf ; 189: 110020, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31809954

RESUMO

Azadirachtin, as the most promising and effective botanical insecticide, exhibits significant growth inhibition activity against agricultural and forestry pests. However, its biochemical effects at the metabolic level compared with those of other insect growth regulators have not been studied. Therefore, in this study, a GC-MS based untargeted metabolomics approach was applied to compare azadirachtin with pyriproxyfen (a juvenile hormone analog) and tebufenozide (a molting hormone analog) in terms of their metabolic effects on Bactrocera dorsalis larvae. The bioactivity of azadirachtin against B. dorsalis larvae was significantly different than those of pyriproxyfen and tebufenozide. A total of 693 mass features were recognized, and 112 metabolites were identified in this study. The results showed that a total of 16, 13 and 10 differentially regulated metabolites corresponding to 12, 5 and 8 pathways occur in Aza versus CK, Pyr versus CK and Teb versus CK group, respectively. Further analysis showed that 6 differentially regulated metabolites corresponding to 5 key pathways could be the primary differential metabolic response of B. dorsalis larvae to the three insect growth regulators. The pathways were myo-inositol corresponding to ascorbate and aldarate metabolism as the specific response of B. dorsalis larvae to azadirachtin; xylitol, xylulose and 3-aminopropionitrile corresponding to pentose and glucuronate interconversions, and cyanoamino acid metabolism as the common responses to azadirachtin and pyriproxyfen; and 3-hydroxypropionic acid and beta-alanine corresponding to propanoate metabolism and beta-alanine metabolism as the specific responses to tebufenozide. The results showed that the metabolic response of B. dorsalis larvae to azadirachitin is closer to that of pyriproxyfen than tebufenozide. The differentially regulated metabolites and pathways responsible for this difference are discussed.


Assuntos
Hidrazinas/farmacologia , Hormônios de Inseto/farmacologia , Inseticidas/farmacologia , Limoninas/farmacologia , Piridinas/farmacologia , Tephritidae/metabolismo , Animais , Larva/efeitos dos fármacos , Larva/metabolismo , Metaboloma/efeitos dos fármacos , Metabolômica , Tephritidae/efeitos dos fármacos
6.
J Sci Food Agric ; 100(3): 1230-1237, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31696522

RESUMO

BACKGROUND: Ensuring the yield, quality, and profitability of okra by preventing and controlling pests with the application of insecticides has increased in the last decade. Some insecticide residues might remain in edible parts of okra (fruits) and lead to several potential human health problems. Therefore, research on the residue behaviour, risk assessment and removal approach of insecticides on okra fruits is important for food safety, together with the proper application and residual elimination of insecticides in okra. RESULTS: A simple liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was established and validated for determining the tebufenozide residues in okra fruits. The recoveries of tebufenozide in okra fruits were >72% with relative standard deviations of 0.6 to 6.1%. The dissipation rates of tebufenozide were different in okra fruits cultivated under open land and glasshouse field conditions because of the discriminating humidity and temperature conditions. The dietary intake of the tebufenozide residues from okra fruit consumption for Chinese consumers was fairly low, with approximately no potential health risk. The processing factor values of washing, blanching, washing + blanching and soaking were all less than one, which indicated that these processes could effectively reduce the residual hydrazide in the okra fruit. CONCLUSION: The developed method for analysing tebufenozide in okra fruits was applicable for field studies on this insecticide. The potential health risk of tebufenozide in okra fruits could be negligible to the health of different age groups of Chinese consumers. The soaking process effectively removed tebufenozide residues from okra fruits. The obtained data will help Chinese governments establish a maximum residue limit of tebufenozide in okra and provide data for the risk assessment and removal of tebufenozide in other crops. © 2019 Society of Chemical Industry.


Assuntos
Abelmoschus/química , Hidrazinas/análise , Inseticidas/análise , Resíduos de Praguicidas/análise , Inocuidade dos Alimentos , Frutas/química , Humanos , Medição de Risco
7.
Biomed Chromatogr ; 33(7): e4522, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30821836

RESUMO

We developed an analytical method using liquid-liquid extraction (LLE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect and quantify tebufenozide (TEB) and indoxacarb (IND) residues in animal and aquatic products (chicken muscle, milk, egg, eel, flatfish, and shrimp). The target compounds were extracted using 1% acetic acid (0.1% acetic acid for egg only) in acetonitrile and purified using n-hexane. The analytes were separated on a Gemini-NX C18 column using (a) distilled water with 0.1% formic acid and 5 mm ammonium acetate and (b) methanol with 0.1% formic acid as the mobile phase. All six-point matrix-matched calibration curves showed good linearity with coefficients of determination (R2 ) ≥0.9864 over a concentration range of 5-50 µg/kg. Intra- and inter-day accuracy was expressed as the recovery rate at three spiking levels and ranged between 73.22 and 114.93% in all matrices, with a relative standard deviation (RSD, corresponding to precision) ≤13.87%. The limits of quantification (LOQ) of all target analytes ranged from 2 to 20 µg/kg, which were substantially lower than the maximum residue limits (MRLs) specified by the regulatory agencies of different countries. All samples were collected from different markets in Seoul, Republic of Korea, and tested negative for tebufenozide and indoxacarb residues. These results show that the method developed is robust and may be a promising tool to detect trace levels of the target analytes in animal products.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Resíduos de Drogas/análise , Análise de Alimentos/métodos , Hidrazinas/análise , Oxazinas/análise , Espectrometria de Massas em Tandem/métodos , Animais , Galinhas , Resíduos de Drogas/química , Resíduos de Drogas/isolamento & purificação , Contaminação de Alimentos/análise , Hidrazinas/química , Hidrazinas/isolamento & purificação , Limite de Detecção , Modelos Lineares , Extração Líquido-Líquido , Oxazinas/química , Oxazinas/isolamento & purificação , Reprodutibilidade dos Testes
8.
Ecotoxicol Environ Saf ; 134P1: 204-212, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27636325

RESUMO

The novel nonsteroidal ecdysone agonist tebufenozide is capable of controlling a wide range of lepidopteran pests. However its intensive use in vegetables has raised concerns towards the safety of food and environment. Here, we developed an easy and reliable method to analyze tebufenozide in cabbage and soil by reversed-phase high performance liquid chromatography (HPLC). The average recoveries of tebufenozide ranged from 72.01% to 101.10% with the relative standard deviations (RSD)<6%, and the LOD and LOQ were 0.02µgg-1 and 0.05µgg-1, respectively. According to the dissipation study, the half-lives of tebufenozide were 2.96 and 4.08 d in cabbage and 4.95-7.70d in soil, respectively. The final residues were determined below the maximum residue limit (MRL) (0.5mgkg-1) after a pre-harvest interval (PHI) of 7d. Moreover, its major metabolites were identified by liquid chromatography tandem mass spectrometry (LC-MS/MS) on LTQ-Orbitrap XL, which leading to the first report of the degradation pathway of tebufenozide in cabbage. The present study is expected to provide basic data for the use guidance and safety evaluation of tebufenozide in agricultural crops and environment.

9.
Ecotoxicol Environ Saf ; 129: 180-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27043174

RESUMO

Tebufenozide is considered an environmentally friendly pesticide due to its specificity on target insects, but the effects on human are well studied. Studies on the toxicity of tebufenozide at molecular and cellular level is poorly understood. The present study reveals non-selective cytotoxic effects of tebufenozide, and the apoptotic mechanism induced by tebufenozide on HeLa and Tn5B1-4 cells. We demonstrate that the viability of HeLa and Tn5B1-4 cells is inhibited by tebufenozide in a time- and concentration-dependent manner. Intracellular biochemical assays showed that tebufenozide-induced apoptosis of two cell lines concurrent with a decrease in the mitochondrial membrane potential and an increase reactive oxygen species generation, the release of cytochrome-c into the cytosol and a marked activation of caspase-3. These results indicate that a mitochondrial-dependent intrinsic pathway contributes to tebufenozide induced apoptosis in HeLa and Tn5B1-4 cells and suggests potential threats to ecosystems and human health.


Assuntos
Bioensaio , Hidrazinas/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Citocromos c/metabolismo , Células HeLa , Humanos , Inseticidas/toxicidade , Lepidópteros/citologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
10.
Bioorg Med Chem ; 23(20): 6594-601, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26404412

RESUMO

The metabolites of tebufenozide, a model compound, formed by the yeast-expressed human CYP3A4 and CYP2C19 were identified to clarify the substrate recognition mechanism of the human cytochrome P450 (CYP) isozymes. We then determined whether tebufenozide metabolites may be predicted in silico. Hydrogen abstraction energies were calculated with the density functional theory method B3LYP/6-31G(∗). A docking simulation was performed using FRED software. Several alkyl sites of tebufenozide were hydroxylated by CYP3A4 whereas only one site was modified by CYP2C19. The accessibility of each site of tebufenozide to the reaction center of CYP enzymes and the susceptibility of each hydrogen atom for metabolism by CYP enzymes were evaluated by a docking simulation and hydrogen abstraction energy estimation, respectively.


Assuntos
Simulação por Computador , Citocromo P-450 CYP2C19/metabolismo , Citocromo P-450 CYP3A/metabolismo , Hidrazinas/análise , Hidrazinas/metabolismo , Humanos , Simulação de Acoplamento Molecular , Software
11.
J Econ Entomol ; 108(1): 277-85, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26470131

RESUMO

The codling moth, Cydia pomonella (L.), is the key pest of apple production worldwide. Insecticide resistance has been reported in all producing countries, based on five different mechanisms. Codling moth in Chile has resistance to azinphos-methyl and tebufenozide in post-diapausing larvae. However, there are no studies about the susceptibility of these populations to insecticides from other chemical groups. Therefore, the efficacy of azinphos-methyl, chlorpyrifos-ethyl, esfenvalerate, methoxyfenozide, tebufenozide, and thiacloprid on neonate and post-diapausing larvae from six field populations was investigated, and identified resistance mechanisms in this species were evaluated. Neonate larvae were susceptible to all insecticides studied, but post-diapausing larvae from four populations were resistant to chlorpyrifos, one of them was also resistant to azinphos-methyl, and another one was resistant to tebufenozide. The acetylcholinesterase insensitivity mutation was not detected, and the sodium channel knockdown resistance mutation was present in a low frequency in one population. Detoxifying enzymatic activity of glutathione S-transferases, esterases, and cytochrome P-450 monooxygenases in adults differed among populations, but chlorpyrifos resistance was associated only with a decreased esterase activity as shown by a significant negative correlation between chlorpyrifos mortality and esterase activity.


Assuntos
Resistência a Inseticidas/fisiologia , Mariposas/enzimologia , Animais , Feminino , Masculino , Mariposas/genética , Organofosfatos
12.
Food Sci Biotechnol ; 33(3): 557-567, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38274176

RESUMO

The effects of milling, washing, and cooking on etofenprox, flubendiamide, and tebufenozide levels in brown and polished rice were investigated by HPLC using a UV detector. The reduction rates of etofenprox, flubendiamide, and tebufenozide after milling were 68.74-93.16%, 64.49-90.25%, and 69.74-92.58%, respectively, 11.64-41.44%, 31.36-65.37%, and 31.61-73.79%, respectively, after washing brown rice, and 30.85-82.08%, 52.13-83.05%, and 43.04-83.89%, respectively, after washing polished rice. The residue levels of the three pesticides in brown rice decreased after electric and pressure cooking by 56.49 and 54.41%, 75.80 and 73.42%, and 70.01 and 71.27%, respectively, and the corresponding levels in polished rice decreased after electric and pressure cooking by 85.58 and 85.82%, 86.70 and 87.06%, and 89.89 and 89.68%, respectively. In conclusion, various processing methods decrease the residual levels of etofenprox, flubendiamide, and tebufenozide in rice.

13.
Mol Ther Methods Clin Dev ; 32(1): 101202, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38374964

RESUMO

The transgene toggling device is recognized as a powerful tool for gene- and cell-based biological research and precision medicine. However, many of these devices often operate in binary mode, exhibit unacceptable leakiness, suffer from transgene silencing, show cytotoxicity, and have low potency. Here, we present a novel transgene switch, SIQ, wherein all the elements for gene toggling are packed into a single vector. SIQ has superior potency in inducing transgene expression in response to tebufenozide compared with the Gal4/UAS system, while completely avoiding transgene leakiness. Additionally, the ease and versatility of SIQ make it possible with a single construct to perform transient transfection, establish stable cell lines by targeting a predetermined genomic locus, and simultaneously produce adenovirus for transduction into cells and mammalian tissues. Furthermore, we integrated a cumate switch into SIQ, called SIQmate, to operate a Boolean AND logic gate, enabling swift toggling-off of the transgene after the removal of chemical inducers, tebufenozide and cumate. Both SIQ and SIQmate offer precise transgene toggling, making them adjustable for various researches, including synthetic biology, genome engineering, and therapeutics.

14.
J Agric Food Chem ; 72(3): 1462-1472, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38197605

RESUMO

Insects' lipids, including fatty acids, as the second largest constituents in insects, play a variety of fundamental and vital functions. However, there is a lack of reports on the effects of insect growth regulators on fatty acid profiles and metabolic mechanisms. Therefore, in this study, a comparative study of three growth regulators, azadirachtin, pyriproxyfen, and tebufenozide, on fatty acids was carried out using a targeted metabolomics approach to fill this gap. The results showed that when exposed to azadirachtin, pyriproxyfen, and tebufenozide, there were 14, 17, and 11 differentially regulated fatty acids, respectively. The pathway of biosynthesis of unsaturated fatty acids was the common shared pathway, while fatty acid biosynthesis and linoleic acid metabolism were the specific pathways affected by the 3 insect growth regulators. Therefore, the results could be helpful to deepen the effects of azadirachtin and insect growth regulators on terrestrial insects.


Assuntos
Ácidos Graxos , Hidrazinas , Hormônios Juvenis , Limoninas , Piridinas , Tephritidae , Animais , Hormônios Juvenis/farmacologia , Larva , Ácidos Graxos/metabolismo , Insetos , Metaboloma
15.
Biol Open ; 11(3)2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35099005

RESUMO

The inflammatory response is a vital defense mechanism against trauma and pathogen induced damage, but equally important is its appropriate resolution. In some instances of severe trauma or sustained infection, inappropriate and persistent activation of the immune response can occur, resulting in a dangerous systemic inflammatory response. Untreated, this systemic inflammatory response can lead to tissue damage, organ shutdown, and death. Replicating this condition in tractable model organisms can provide insight into the mechanisms involved in the induction, maintenance, and resolution of inflammation. To that end, we developed a non-invasive, inducible, and reversible model of systemic inflammation in zebrafish. Using the Gal4-EcR/UAS system activated by the ecdysone analog tebufenozide, we generated transgenic zebrafish that allow for chemically induced, ubiquitous secretion of the mature form of zebrafish interleukin-1ß (Il-1ßmat) in both larval and adult developmental stages. To ensure a robust immune response, we attached a strong signal peptide from the Gaussia princeps luciferase enzyme to promote active secretion of the cytokine. We observe a dose-dependent inflammatory response involving neutrophil expansion accompanied by tissue damage and reduced survival. Washout of tebufenozide permits inflammation resolution. We also establish the utility of this model for the identification of small molecule anti-inflammatory compounds by treatment with the immunosuppressant rapamycin. Taken together, these features make this model a valuable new tool that can aid in identifying potential new therapies while broadening our understanding of systemic inflammation, its impact on the immune system, and its resolution.


Assuntos
Inflamação , Peixe-Zebra , Animais , Animais Geneticamente Modificados , Inflamação/genética , Síndrome de Resposta Inflamatória Sistêmica , Proteínas de Peixe-Zebra/genética
16.
Insect Sci ; 29(4): 1096-1104, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34730283

RESUMO

ABC transporters have been suggested to be involved in insecticide detoxification in different insect species mainly based on the indirect observation of transcriptional upregulation of ABC gene expression in response to insecticide exposure. Previous studies performed by us and others in the red flour beetle, Tribolium castaneum, have analyzed the function of TcABCA-C and TcABCG-H genes using RNA interference (RNAi) and demonstrated that specific TcABCA and TcABCC genes are involved in the elimination of the pyrethroid tefluthrin and the benzoylurea diflubenzuron, because gene silencing increased the beetle's susceptibility to the insecticides. In this study, we focused on the potential functions of TcABCA-C genes in detoxification of the pyrethroid cyfluthrin (CF), the organophosphate malathion (MAL) and the diacylhdyazine tebufenozide (TBF). Analysis of transcript levels of selected TcABCA-C genes in response to treatment with these three chemically unrelated insecticides revealed that some genes were particularly upregulated after insecticide treatment. In addition, the ABC inhibitor verapamil synergized significantly the toxicity of MAL but only negligibly CF and TBF toxicities. Finally, silencing of two TcABCC genes by RNAi revealed a significant increase in susceptibility to MAL. In contrast, we did not observe a significant increase in insecticide-induced mortalities when knocking down TcABC genes in larvae treated with CF or TBF, although they were upregulated in response to insecticide treatment. Our results suggest that two pleiotropic ABCC transporters expressed in metabolic and excretory tissues contribute to the elimination of MAL.


Assuntos
Besouros , Inseticidas , Piretrinas , Tribolium , Animais , Inseticidas/farmacologia , Malation/metabolismo , Malation/toxicidade , Tribolium/genética , Tribolium/metabolismo
17.
EFSA J ; 19(11): e06920, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34868370

RESUMO

In 2018, the risk assessment for tebufenozide in light of confirmatory data requested following approval in accordance with Article 6(1) of Directive 91/414/EEC and Article 6(f) of Regulation (EC) No 1107/2009 concluded that based on the submitted data, the metabolite RH-2651 has to be considered as a relevant groundwater metabolite since the absence of genotoxic potential in vivo was not fully demonstrated. Following further considerations during the decision-making process, the European Commission asked EFSA on 14 July 2021 to provide its scientific view on the genotoxic potential of the metabolite RH-2651 following consideration of new experimental data submitted by the applicant under Article 21(2) of Regulation (EC) No 1107/2009. Based on the available data, it is concluded that metabolite RH-2651 does not have genotoxic potential and therefore is not automatically considered a relevant groundwater metabolite.

18.
EFSA J ; 19(1): e06400, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33537071

RESUMO

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Nisso Chemical Europe GmbH submitted a request to the competent national authority in Italy to modify the existing maximum residue levels (MRLs) for the active substance tebufenozide in apricots and peaches. The data submitted in support of the request were found to be sufficient to derive MRL proposals for apricots and peaches. Adequate analytical methods for enforcement are available to control the residues of tebufenozide on the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of tebufenozide according to the reported agricultural practice is unlikely to present a risk to consumer health.

19.
Pest Manag Sci ; 77(6): 2955-2963, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33620766

RESUMO

BACKGROUND: ATP-binding cassette transporter (ABC transporter) subfamilies ABCA-C and ABCG-H have been implicated in insecticide detoxification, mostly based on findings of elevated gene expression in response to insecticide treatment. We previously characterized TcABCA-C genes from the model beetle and pest Tribolium castaneum and demonstrated that TcABCA and TcABCC genes are involved in the elimination of diflubenzuron, because RNA interference (RNAi)-mediated gene silencing increased susceptibility. In this study, we focused on the potential functions of TcABCG and TcABCH genes in insecticide detoxification. RESULTS: When we silenced the expression of TcABCG-H genes using RNAi, we noticed a previously unreported developmental RNAi phenotype for TcABCG-4F, which is characterized by 50% mortality and ecdysial arrest during adult moult. When we knocked down the Drosophila brown orthologue TcABCG-XC, we did not obtain apparent eye colour phenotypes but did observe a loss of riboflavin uptake by Malpighian tubules. Next, we determined the expression profiles of all TcABCG-H genes in different tissues and developmental stages and analysed transcript levels in response to treatment with four chemically unrelated insecticides. We found that some genes were specifically upregulated after insecticide treatment. However, when we determined insecticide-induced mortalities in larvae that were treated by double-stranded RNA injection to silence those TcABCG-H genes that were upregulated, we did not observe a significant increase in susceptibility to insecticides. CONCLUSION: Our findings suggest that the observed insecticide-dependent induction of TcABCG-H gene expression reflects an unspecific stress response, and hence underlines the significance of functional studies on insecticide detoxification. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Besouros , Diflubenzuron , Inseticidas , Tribolium , Animais , Inseticidas/farmacologia , Larva/genética , Interferência de RNA , Tribolium/genética
20.
Food Chem Toxicol ; 120: 64-70, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29958988

RESUMO

Tebufenozide, a newly-developed nonsteroidal ecdysone agonist, is in pre-regulation phase (before approval for use) on stem lettuce in China. Aiming at the safe application of tebufenozide, the dissipation and terminal residue trials on stem lettuce were performed under good agricultural practice (GAP). The dissipation trials shown that tebufenozide was rapidly degraded in stem lettuce, with half-lives of 5.0-8.2 days. Pre-regulation dietary exposure risk assessments were evaluated to recommend maximum residue limits (MRLs) based on risk quotients (RQ) method. Relevant toxicological parameters including ADI (acceptable daily intake) and ARfD (acute reference dose) were applied to assess the potential dietary exposure risk. The results indicated the chronic dietary exposure risk probability (RQc) of tebufenozide ranged from 36.4% to 70.0%. The acute dietary exposure risk probability (RQa) of tebufenozide was 2.88%-8.49% in lettuce stems and 14.0%-20.0% in lettuce leaves, respectively. On the basis of supervised field trial data and dietary exposure risk assessment results, the MRLs of tebufenozide were recommended as 3 mg/kg for lettuce stems and 10 mg/kg for lettuce leaves, respectively. The results demonstrated that the dietary exposure risk of tebufenozide used in stem lettuce under GAP was negligible and would not pose unacceptable health risk to Chinese consumers.


Assuntos
Exposição Dietética , Contaminação de Alimentos/análise , Hidrazinas/análise , Inseticidas/análise , Lactuca/química , Resíduos de Praguicidas/análise , China , Cromatografia Líquida , Ecossistema , Humanos , Hidrazinas/toxicidade , Inseticidas/toxicidade , Resíduos de Praguicidas/toxicidade , Folhas de Planta/química , Caules de Planta/química , Padrões de Referência , Reprodutibilidade dos Testes , Medição de Risco , Espectrometria de Massas em Tandem
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