ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
·
2021
·Vol. 41
·期 1
·230-239
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IF 3.742
Siqi Wu,Huizhen Li,Jing You
Fipronil has been frequently detected in waterways worldwide at concentrations that threaten aquatic organisms, yet the metabolic behavior of fipronil enantiomers in aquatic organisms is largely unknown, which is of significance in enantioselective toxicity evaluation. We quantitatively identified the specific cytochrome P450 (CYP) isozymes involved in metabolizing fipronil enantiomers in tilapia by combining in vitro metabolic kinetic assays and molecular docking. Inhibition studies suggested that CYP1A enzyme was the main isoform catalyzing metabolism of fipronil and that CYP3A contributed in a limited way to the metabolism in fish liver S9. Both the dissipation rate constant and the maximum metabolic velocity of R -(−)-fipronil were greater than those of S -(+)-fipronil in tilapia liver S9, suggesting that tilapia selectively metabolized R -(−)-fipronil. The CYP1A1 isozyme exhibited the highest binding capacity to R -(−)-fipronil and S -(+)-fipronil (binding energy ‒9.39 and ‒9.17 kcal/mol, respectively), followed by CYP1A2 (‒7.30 and ‒6.94 kcal/mol, respectively) and CYP3A4 (‒7.16 and ‒6.91 kcal/mol, respectively). The results of in vitro metabolic assays and molecular docking were consistent, that is, CYP1A, specifically CYP1A1, exhibited a higher metabolic capacity to fipronil than CYP3A, and fish liver S9 selectively metabolized R -(−)-fipronil. The present study provides insight into the enantioselective metabolic behavior and toxicological implications of the in vitro metabolic kinetics of fipronil in fish. Environ Toxicol Chem 2022;41:230–239. © 2021 SETAC
研究领域:
环境毒理学
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水生毒理学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Analytical Methods
·
2020
·Vol. 12
·期 46
·5581-5590
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IF 2.596
Xin Pan,Zhangjun Wang,Chao Chen,Hui Li,Xianxin Li,Quanfeng Zhang,Xiufen Wang,Yanan Zhang
Neonicotinoid and fipronil insecticides have been consumed worldwide, particularly in China. There is growing interest in the environmental research community about the occurrence, sources, and risks of neonicotinoids and fipronil. A new method based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and disc solid phase extraction (SPE) techniques were developed for the determination of neonicotinoids and fipronil in seawater in this research. The effects of the styrene divinyl benzene-reverse phase sulfonated (SDB-RPS) membrane-based solid phase extraction optimization process and the HPLC separation parameters on the detection results of the target compounds were studied. Under the optimized conditions, the detection limit of this method for 12 target compounds ranged from 0.05 ng L−1 to 0.50 ng L−1 and absolute recovery was achieved from 58.9–106.5%. The results proved that this method can effectively detect neonicotinoid and fipronil pesticides in seawater. At the same time, dinotefuran, nitenpyram, thiamethoxam, imidacloprid, thiacloprid, fipronil and its metabolites were found in seawater samples from the Yangtze River Estuary and the adjacent sea area. Among them, the total concentration of neonicotinoid insecticides ranged from ND-12.45 ng L−1 and the average total concentration was 3.5 ng L−1; the total concentration of fipronil and its metabolites ranged from ND-2.45 ng L−1, and the average total concentration was 0.79 ng L−1. The results showed that there was contamination of neonicotinoids and fipronil in the Yangtze River Estuary and its adjacent area.
研究领域:
环境科学
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分析化学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
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2022
·Vol. 30
·期 7
·18499-18508
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IF 5.19
Suo Decheng,Song Zhandeng,Xiao Zhiming,Zhuang Fenting,Fan Li,Fan Xia
A method based on a multi-mechanism impurity adsorption and ultra-performance liquid chromatography–tandem mass spectrometry was established to detect fipronil and four of its metabolites in chicken feathers. This method was successfully applied to the depletion study of fipronil in feathers of laying hens. Fipronil and two metabolites were found in feathers during treatment. Fipronil concentrations in feathers increased during medication and then regularly decreased during withdrawal, and they were still detected on the 14th day after withdrawal. High residue concentrations were also present in feathers on day 23 of the experimental period. Pollution sources of fipronil can be inferred on the basis of the residue ratio of fipronil metabolites from different pollution modes. Result shows that feathers were an effective matrix for residue monitoring and risk analysis of fipronil in animals and the environment.
研究领域:
动物学
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环境科学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2025
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IF 2.8
Meichen Liu,Yingxia Guo,Ziyi Niu,Yufeng Guo,Shuang Feng,Xiaoyan Zhang,Jiansong You,Lei Yin,Hongyu Xue,Meiyun Shi
A sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry cubed (UPLC-MS 3 ) assay was established for detection of fipronil in zebrafish tissue samples. Following protein precipitation pretreatment, the concentrations of fipronil in various zebrafish tissue samples were quantified by the developed UPLC-MS 3 assay. Fipronil was monitored by MS 3 transition ( m/z 435.0 → 398.9 → 330.0) with a ± 1.0 Da isolation window for secondary product ions. Chromatographic separation was achieved with 0.1 % formic acid-water ( v /v) as the aqueous phase and acetonitrile as the organic phase. Gradient elution with C 18 column was employed for separation of fipronil and probenecid (internal standard, IS). Method validation demonstrated excellent linearity over the range of 0.1–10 ng/mL (r 2 > 0.995), with the accuracies ranging from −10.33 % to 3.17 % and precisions between 3.25 % and 11.34 %. Consistent extraction recoveries (89.92–113.49 %) and acceptable matrix effects (92.54–110.27 %) were observed across all tested matrices. The implementation of MS 3 scanning significantly enhanced specificity by eliminating endogenous interference compared to conventional MRM detection. The successful application of this method in zebrafish tissue distribution studies confirmed its reliability for environmental toxicology research. This MS 3 -based approach provides a robust analytical platform for investigating biodistribution of fipronil in aquatic models.
研究领域:
分析化学
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环境科学
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毒理学
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产品关联
DOI
PubMed
高影响因子
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
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2023
·Vol. 37
·期 13
·e9518
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IF 2
Lihua Qu,Xiaoyu Qi,Li Zhao,Yu Zhang,Ronghua Zhuge,Zhihui Hao,Congmin Liu
Rationale The residues of fipronil and its metabolites in chicken eggs pose a threat to human health, so regular monitoring is necessary. However, the pretreatments of the existing detection methods are complex and time-consuming. A simple and streamlined pretreatment method is needed to improve the detection efficiency. Method A rapid, efficient, and facile approach employing the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method with online solid-phase extraction liquid chromatography tandem Q Exactive Orbitrap high-resolution mass spectrometry (online-SPE-LC-HRMS) was established and evaluated for the determination of fipronil, fipronil-desulfinyl, fipronil-sulfone, and fipronil-sulfide in chicken eggs. An improved sample preparation technique combining QuEChERS and online-SPE was developed. Negative targeted ion fragmentation scanning and targeted-selected ion monitoring of HRMS were adopted to identify and quantify the target analytes. Results The proposed pretreatment method took a few steps in <13 min to achieve excellent recoveries and negligible interference. High selectivity was acquired with the adoption of Q/Orbitrap HRMS. The limit of quantification (LOQ) of the analytes was 2.5 μg kg −1 , meeting the detection requirements of the maximum residue level enacted by the Codex Alimentarius Commission, Japan, and the United States for the sum of fipronil and its metabolites. Extraction recoveries at three spiked concentration levels were within 84.56% to 93.84%, with relative standard deviation ≤5.87%. Conclusion The established method is efficient and easy to operate and displays satisfactory LOQs, recoveries, accuracy, and precision. This approach serves as a reference method for monitoring eggs while providing potential solutions for fipronil determination in more complicated matrices.
研究领域:
食品安全
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分析化学
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毒理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2018
·
IF 3.412
Bo Zhang,Lei Zhang,Lujue He,Xiaodong Yang,Yali Shi,Shaowei Liao,Shan Yang,Jiagao Cheng,Tianrui Ren
Fipronil is an efficient phenylpyrazole insecticide that acts on insect γ-aminobutyric acid (GABA) receptors (GABARs) and has low toxicity to mammals but high toxicity to nontarget organisms such as fish. To develop novel efficient low-toxicity insecticides, it is necessary to determine the detailed toxic mechanism at the molecular target level. In this work, methods including affinity chromatography, fluorescent-labeled binding assays, and molecular modeling were integrated to explore the binding of fipronil to GABARs in fish (Aristichthys nobilis) and insects (Musca domestica). Affinity chromatography revealed that fipronil acts on two different subunits of GABARs in fish and M. domestica. Moreover, fluorescence assays revealed that fipronil exhibits similar affinity to the two GABARs. The Kd and Bmax of fipronil binding to the A. nobilis GABAR were 346 ± 6 nmol/L and 40.6 ± 3.5 pmol/mg of protein, respectively. And the Kd and Bmax of fipronil binding to the GABAR in M. domestica brain were 109 ± 9 nM and 21.3 ± 2.5 pmol/mg of protein, respectively. In addition, similar fipronil binding positions but different binding modes were observed in docking studies with Brachydanio rerio var. and M. domestica GABARs. These findings indicated similar interactions of fipronil with fish and insects, leading to high toxicity. The different binding features of fipronil between the two species might be helpful for the design and development of highly selective insecticides with low toxicity to fish.
研究领域:
环境毒理学
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分子生物学
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药物化学
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2020
·
IF 3.594
Cong Wang,Yao Lin,Yichao Wang,Ting-Fu Jiang,Zhihua Lv
A novel and sensitive dispersive liquid–liquid micro-extraction (DLLME) combined with 19 F quantitative nuclear magnetic resonance spectroscopy (qNMR) method was developed and validated for determination of fipronil and its metabolites in chicken egg. The qNMR analysis was carried out under the optimum experimental conditions including deuterated DMSO as solvent, calibrated 4′-Bromo-2′-fluoro acetanilide as internal standard, d 1 (relaxation delay) = 1 s, and NS (number of scan) = 1024. The analytes were extracted in a mixed emulsion system of extraction solvent (chloroform) and dispersing solvent (acetonitrile). A demulsifier (acetonitrile) was added to break up the emulsion. Then, the lower layer (chloroform) was collected and analyzed by qNMR. Important parameters affecting the extraction efficiency of DLLME were investigated in detail. Although the pretreatment time is relatively long, we have obtained satisfactory experimental results. The newly established method has a good linear relationship, the linear correlation coefficient r is between 0.9972 and 0.9995, the minimum detection limit is 0.025 μg mL −1 , and the extraction reproducibility is good (RSD ≤ 3.67%, n = 6). The optimized new method was applied to the analysis of fipronil and its metabolites in chicken egg. The recoveries of spiked samples were between 97.49% and 103.0%, and satisfactory experimental results were obtained. The obtained results show that the establishment of this method provides an excellent alternative for the detection of fipronil and its metabolites in chicken egg.
研究领域:
分析化学
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食品安全
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
·
IF 8.2
Yun Huang,Li Xu,Junyue Zheng,Peizhuo Wu,Yu Zhang,Lihong Qiu
As we known, inducibility is an important feature of P450 genes. Previous studies indicated that CYP6B7 could be induced and involved in fenvalerate detoxification in Helicoverpa armigera . However, the regulatory mechanism of CYP6B7 induced by fenvalerate is still unclear. In this study, CYP6B7 promoter of H. armigera was cloned and the cis -acting element of fenvalerate was identified to be located between −84 and − 55 bp of CYP6B7 promoter. Subsequently, 33 candidate transcription factors ( CYP6B7 -fenvalerate association proteins, CAPs) that may bind to the cis -acting element were screened and verified by yeast one-hybrid. Among them, the expression levels of several CAPs were significantly induced by fenvalerate. Knockdown of juvenile hormone-binding protein-like (JHBP), RNA polymerase II-associated protein 3 (RPAP3), fatty acid synthase-like (FAS) and peptidoglycan recognition protein LB-like (PGRP) resulted in significant expression inhibition of CYP6B7 , and increased sensitivity of H. armigera to fenvalerate. Co-transfection of reporter gene p (−84/−55) with pFast-CAP showed that JHBP, RPAP3 and PGRP could significantly increase the activity of CYP6B7 promoter. These results suggested that trans -acting factors JHBP, RPAP3 and PGRP may bind with cis -acting elements to regulate the expression of CYP6B7 induced by fenvalerate, and play an important role in the detoxification of H. armigera to fenvalerate.
研究领域:
分子生物学
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昆虫学
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毒理学
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DOI
PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 18
·3223
·
IF 3.06
Xiu Liu,Linya Huang,Hongjun Chen,Na Li,Chao Yan,Chenzhong Jin,Hanhong Xu
To obtain highly selective toxic derivatives of fipronil, a series of Schiff bases with an alkynyl group (3a–3k) were designed and synthesized from 4-ethynylbenzaldehyde (2) and 4-substituted 5-amino-N-arylpyrazole (1a–1k) via a nucleophilic addition elimination reaction in ionic liquids. Utilization of ionic liquids was demonstrated to endow the yield of each compound beyond 50%, which was enhanced over 1.5 times of the synthetic productive rates comparing the conventional method by which longer reactive time was consumed. The derivatives were characterized via nuclear magnetic resonance hydrogen spectroscopy (1H-NMR), carbon-13 nuclear magnetic resonance spectroscopy (13C-NMR), and electrospray ionization high resolution mass spectrometry (ESI-HRMS). The cytotoxicity of these derivatives onTrichoplusia ni(Hi-5) cell andSpodoptera lituracell (SL cell) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) bioassays. The results indicated that several compounds had potential cytotoxicity on Hi-5 cell, especially a 4-ethyl substituted alkynyl Schiff base derivative (3f) that was demonstrated to possess high selective toxicity to the Hi-5 cell than the SL cell. In addition,3fexhibited comparable toxic activity to commercial fipronil on a Hi-5 cell while a little toxic effect on the SL cell, which satisfied the expectation for selective toxicity screening.Keywords:N-arylpyrazole derivatives;schiff base;cytotoxicity;fipronil derivatives
研究领域:
有机化学
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农药学
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毒理学
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产品关联
DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2022
·Vol. 79
·期 1
·125-133
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IF 4.462
Bin Zeng,Ya-Ting Liu,Ze-Rui Feng,Fu-Rong Chen,Shun-Fan Wu,Chris Bass,Cong-Fen Gao
Background Buprofezin, an insect growth regulator, has been widely used to control brown planthopper (BPH), Nilaparvata lugens , one of the most destructive pests of rice crops in Asia. The intensive use of this compound has resulted in very high levels of resistance to buprofezin in the field, however, the underpinning mechanisms of resistance have not been fully resolved. Results Insecticide bioassays using the P450 inhibitor piperonyl butoxide significantly synergized the toxicity of buprofezin in two resistant strains of BPH (BPR and YC2017) compared to a susceptible strain (Sus), suggesting P450s play a role in resistance to this compound. Whole transcriptome profiling identified 1110 genes that were upregulated in the BPR strain compared to the Sus strain, including 13 cytochrome P450 genes, eight esterases and one glutathione S -transferase. Subsequently, qPCR validation revealed that four of the P450 genes, CYP6ER1vA , CYP6CW1 , CYP4C77 , and CYP439A1 were significantly overexpressed in both the BRP and YC2017 strains compared with the Sus strain. Further functional analyses showed that only suppression of CYP6ER1vA , CYP6CW1 , and CYP439A1 gene expression by RNA interference significantly increased the toxicity of buprofezin against BPH. However, only transgenic Drosophila melanogaster expressing CYP6ER1vA and CYP439A1 exhibited significant resistance to buprofezin. Finally, the BPR strain was found to exhibit modest but significant levels of resistance to acetamiprid, dinotefuran and pymetrozine. Conclusions Our findings provide strong evidence that the overexpression of CYP6ER1vA and CYP439A1 contribute to buprofezin resistance in BPH, and that resistance to this compound is associated with low-level resistance to acetamiprid, dinotefuran and pymetrozine. These results advance understanding of the molecular basis of BPH resistance to buprofezin and will inform the development of management strategies for the control of this highly damaging pest. © 2022 Society of Chemical Industry.
研究领域:
昆虫学
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分子生物学
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害虫管理
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2020
·
IF 4.049
Mengyuan Li,Chunliu Yang,Hongyuan Yan,Yehong Han,Dandan Han
A rapid and economic integrated solid-phase extraction (ISPE) method with ionic liquid-thiol-graphene oxide composite (IL-TGO) as a new adsorbent was established for the extraction of fipronil in chicken eggs. In this study, ISPE, a new form of solid-phase extraction, which combined the advantages of pipette-tip solid phase extraction (PT-SPE) and dispersive solid-phase extraction (DSPE), achieving rapid extraction of analyte with only a small amount of adsorbent. The three-dimensional porous IL-TGO was a new ideal adsorbent for fipronil due to the multiple adsorption interactions (π-π interaction, hydrophobic interaction and hydrogen bond), large adsorption capacity and fast adsorption rate. For this ISPE procedure, the analyte was adsorbed by IL-TGO through the pipette tip mode and then eluted through dispersive mode. Under the optimized condition, the proposed method performed following merits: good linearity (r = 0.9999), precision (RSD ≤ 6.3%), high recoveries (83.7% to 97.7%), rapid extraction (16 min), low consumption of adsorbent (3.00 mg of IL-TGO). The excellent recyclability of the ISPE device and the reusability of IL-TGO were observed and high recovery of fipronil (> 90%) was obtained after fifteen cycles. This work might provide promising strategy for the sensitive extraction and analysis of trace levels of fipronil from egg products.
研究领域:
分析化学
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食品安全
✓ 已验证
DOI
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2025
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IF 4.3
Yunshuo Chen,Yachan Gong,Dan Li,Weiwei Feng,Yao Chen,Ting Zhao,Liuqing Yang,Guanghua Mao,Xiangyang Wu
As a typical neonicotinoid insecticide, dinotefuran (DIN) has immunotoxicity, but its immunotoxicity effects on aquatic organisms and its molecular mechanisms are not known. In this study, zebrafish embryos were used as model to reveal its immunotoxicity and its mechanism from the perspective of inflammatory response. Zebrafish larvae were exposed to DIN at environmentally relevant concentrations (0, 2, 200, and 2000 mg/L) for 120 h, followed by comprehensive analyses of immune cell populations, immune marker activities, oxidative stress levels, and gene expression profiles. The results showed that the number of neutrophils and macrophages, two types of innate immune cells, was significantly reduced, and the activities of the immune markers, lysozyme (LYS), immunoglobulin M (IgM), and complement protein C3, were significantly inhibited. The level of oxidative stress in zebrafish larvae was significantly elevated and antioxidant enzyme activities were markedly inhibited in a dose-dependent manner after exposure to DIN. In this case, pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β were also abnormally expressed, and the expression levels of the genes related to the NF-κB pathway and the JNK-STAT pathway, tlr4a, myd88, nf-κb p65, jak1, jak2 , and stat3 , were elevated. The expression levels of genes related to the antioxidant signaling pathway Nrf2-keap1 signaling pathway were suppressed. Taken together, our results suggest that DIN exposure causes damage to the immune system of zebrafish embryos-larvae, generating oxidative stress and inflammatory responses that lead to immunotoxicity.
研究领域:
环境科学
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毒理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）