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JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART B-PESTICIDES FOOD CONTAMINANTS AND AGRICULTURAL WASTES · 2023 · IF 2

Dissipation, residue and dietary risk assessment of difenoconazole in Rosa roxburghii

Qingshan Feng,Lei Han,Qiong Wu,Xiaomao Wu

Rosa roxburghii is a medicinal and edible plant, which is favored by consumers due to its rich vitamin C content. Residues and potential health risks of difenoconazole in the R. roxburghii ecosystem has aroused a concern considering its extensive use for controlling the powdery mildew of R. roxburghii. In this study, the residue of difenoconazole in R. roxburghii and soil was extracted by acetonitrile, purified by primary secondary amine and detected by liquid chromatography-tandem triple quadrupole mass spectrometry. The average recoveries in R. roxburghii and soil matrix varied from 82.59% to 99.63%, with relative standard deviations (RSD) of 1.14%–8.23%. The limit of quantification (LOQ) and detection (LOD) of difenoconazole in R. roxburghii and soil samples were 0.01 mg/kg. The dissipation of difenoconazole followed well the first-order kinetic, with a half-life of 3.99–5.57 d in R. roxburghii and 4.94–6.23 d in soil, respectively. And the terminal residues were <0.01–2.181 mg/kg and 0.014–2.406 mg/kg, respectively. The chronic and acute risk quotient values of difenoconazole were respectively 0.42% and 4.1%, which suggests that the risk was acceptable and safe to consumers. This study provides a reference for the safe and reasonable use of difenoconazole in R. roxburghii production.

研究领域: 植物保护 · 食品安全 · 分析化学
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CHEMICAL PAPERS · 2017 ·Vol. 72 ·期 5 ·1277-1286 · IF 1.258

Preparation and characterization of hydrophilic molecularly imprinted microspheres for difenoconazole

Li Ling,Wang Yan,Liu Xin-Xin,Li Ran-Hong

Hydrophilic molecularly imprinted microspheres (HMIMs) for difenoconazole were prepared by precipitation polymerization using 2-hydroxypropyl methacrylate (HPMA) as functional monomer, ethylene glycol dimethacrylate as cross-linker, azobisisobutyronitrile as initiator, and mixture of butanone and n-heptane (6:4, V:V) as solvent. The morphological particle sizes and structures were determined via scanning electron microscopy, laser particle size analyzer, and Fourier transform infrared spectrometry. The average particle size of HMIMs and hydrophilic molecularly non-imprinted microspheres (HNIMs) were 2.72 and 3.28 μm, respectively. Binding experiments were performed in distilled water to evaluate the adsorption capacity of the obtained microspheres towards difenoconazole. Scatchard model shows the maximum adsorption of HMIMs and HNIMs for difenoconazole are 65.04 and 56.97 mg g −1 . Langmuir isotherm presents Q max of HMIMs and HNIMs are 62.89 and 53.19 mg g −1 . Pseudo-second-order kinetic model displayed a good linear relation and illustrated that the adsorption process of HMIMs is belong to chemical adsorption. Selectivity analysis presented HMIM1 possessed highly specific binding sites for difenoconazole.

CAS / MDL: 97-90-5 27813-02-1
研究领域: 材料科学 · 环境科学
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JOURNAL OF CHEMICAL AND ENGINEERING DATA · 2023 · IF 2.6

Solubility Measurement and Calculation of Difenoconazole in Several Solvents at 278.15 to 323.15 K

Zhenghui Li,Chunjuan Huang

The equilibrium solubility (mole fraction) of difenoconazole in methanol, ethanol, n-propanol, isopropanol, N,N-dimethylformamide (DMF), acetonitrile, acetone, propylene glycol (PG), ethylene glycol (EG), and water and methanol/ethanol/isopropanol/PG + water was measured by isothermal saturation method at 278.15–323.15 K under 101.2 kPa. The solubility of difenoconazole in pure solvents increased with increasing temperature, and the solubility in mixed solvents was proportional to the temperature and the ratio of cosolvents. The solubility of difenoconazole in pure solvents was correlated with the Apelblat, NRTL, and λh models. The Jouyban-Acree (JA), modified Apelblat-Jouyban-Acree (AJA), and van’t Hoff-Jouyban-Acree (VJA) models were applied to calculate the solubility of difenoconazole in mixtures. Solvent effect analysis as a powerful tool was used to estimate solvent–solvent and solvent–solute interactions at the molecular level, and the results showed that nonspecific dipolarity/polarizability interactions were the main influencing factor.

CAS / MDL: 67-64-1
研究领域: 化学工程 · 物理化学 · 药物化学
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TALANTA · 2018 · IF 4.244

Surface-enhanced Raman scattering of core-shell Au@Ag nanoparticles aggregates for rapid detection of difenoconazole in grapes

Kaiqiang Wang,Da-Wen Sun,Hongbin Pu,Qingyi Wei

The residual of pesticides in fruit and vegetables is one of the major food safety concerns for consumers. There is a demand for easy and rapid analytical methods to sense pesticide residues in foods. In this study, a core-shell Au@Ag nanoparticles aggregates (Au@AgNAs) based surface-enhanced Raman scattering (SERS) method was developed to detect trace amount of difenoconazole . Results suggested that by targeting the characteristic peaks at 700 and 808 cm −1 , the logarithmic SERS signal intensities and logarithmic difenoconazole concentrations in the range from 5 × 10 −7 to 2.5 × 10 −5 M showed linear relationship with the coefficient of determination ( R 2 ) of 0.990 and 0.985, and limit of detection (LOD) values of 5.01 × 10 −8 and 2.8 × 10 −8 M, respectively. The Quick Easy Cheap Effective Rugged and Safe (QuEChERS) sample preparation method was used to extract difenoconazole in grapes for SERS measurements. The LOD of difenoconazole in grapes using this developed method was as low as 48 μg/kg, which was significantly lower than the maximum residue limit (MRL) values prescribed by European Union and China. This study demonstrated that the Au@AgNAs-based SERS method can be used as a simple, rapid and sensitive approach for sensing trace contaminants in food.

研究领域: 食品安全 · 分析化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SCIENCE OF THE TOTAL ENVIRONMENT · 2021 · IF 7.963

Stereoselective effects of fungicide difenoconazole and its four stereoisomers on gut barrier, microbiota, and glucolipid metabolism in male mice

Hu Zhang,Guiling Yang,Zhiwei Bao,Yuanxiang Jin,Jianmei Wang,Jing Chen,Mingrong Qian

Difenoconazole is a commonly used triazole fungicide that consists of four stereoisomers [( 2S,4S )-, ( 2S,4R )-, ( 2R,4R )-, and ( 2R,4S )-isomers] with different bioactivity. For example, the toxicity of the ( 2R,4S )-isomer to fish is approximately seven times higher than that of the ( 2S,4S )-isomer. However, the stereoselective toxic effects of difenoconazole stereoisomers on mammals have received little attention. In the present study, adult male mice were orally treated with a mixture of the four stereoisomers or each stereoisomer individually (0, 30, or 100 mg/kg/d) by gavage for 28 days. Pathological staining of the liver sections showed that the ( 2R,4R )-isomer caused lipid droplet accumulation. The mixture or each individual stereoisomers decreased the levels of amino acids and acyl-carnitine in serum. Moreover, the ( 2S,4R )-, ( 2R,4R )-, and ( 2R,4S )-isomers affected intestinal permeability, causing decreases in mucus secretion and tight junction protein expression in colon. Analysis of the gut microbiota composition showed that the stereoisomers caused decreases of OTU numbers and observed species at different levels. Interestingly, difenoconazole and its four stereoisomers reduced the relative abundance of Bacteroidetes at the phylum level and some short-chain fatty acid (SCFA)-producing bacteria. Taking the findings together, 2R -difenoconazole with strong bioactivity against pathogenic fungi also had significant effects in mammals, disrupting hepatic lipid metabolism, intestinal permeability, and gut microbiota. It is concluded that the health risks of the four difenoconazole stereoisomers to mammals should not be overlooked.

研究领域: 毒理学 · 环境科学 · 代谢组学
✓ 已验证 DOI PubMed 高影响因子
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CHEMOSPHERE · 2022 · IF 8.943

Highly efficient in-situ cleaner degradation of difenoconazole by two novel dominant strains: Microflora diversity, monoclonal isolation, growth factor optimization, intermediates, and pathways

Xiaoxin Chen,Shan Peng,Miao Liu,Lei Wang,Kyongjin Pang,Liyuan Zhang,Ziyi Cui,An Liu

The non-point source pollution of difenoconazole (DIF) has become a serious environmental issue , increasingly causes indelible damages to eco-environment and human health due to its toxicity, persistence, and biomagnification . An eco-friendly, cost-effective, and efficient control technology is imperative towards a cleaner and sustainable agricultural production. Herein, a dominant microflora of efficiently degrading DIF was successfully screened, and its microbial diversity was investigated. Two novel degrading strains were isolated and identified as Phyllobacterium sp. (T-1) and Aeromonas sp. (T-2). The results of growth factor optimization indicated that the degradation rates of DIF (C 0  = 20 mg/L) by strain T-1 and T-2 were up to 96.32% and 97.86% within 14 d, respectively, under the optimal conditions. Moreover, there no obvious synergy between strain T-1 and strain T-2. From catalytic kinetics of enzymes, the intracellular enzyme of strain T-1 dominated the degradation of DIF (C 0  = 20 mg/L) entirely with the degradation rate of 82.4% (48 h), the extracellular enzyme showed little catalytic activity . However, the degrade rates of DIF (C 0  = 20 mg/L) by both intracellular and extracellular enzymes of strain T-2 were 77.99% and 26.73% within 48 h, respectively. Moreover, these enzymes remained an undiminished catalytic activity within 48 h. DIF was degraded by strain T-1 to three main transformation products (DIF-TPs 406, DIF-TPs 216, and DIF-TPs 198) undergoing hydroxyl substitution, hydrolysis, cleavage of ether bond between benzene rings, and rearrangement, while two additional products (DIF-TPs 281 and DIF-TPs 237) were generated with the biodegradation of strain T-2, excepting for DIF-TPs 406 and DIF-TPs 216, involving hydrolysis, hydroxylation, and ether bond cleavage between benzene rings. Moreover, QSAR simulation showed that the by-products were almost much lower toxicity or even non-toxic to three typical aquatic organisms (fish, daphnia, and green algae) than DIF. This study not only provides an in depth understanding of DIF bioelimination, but also be instrumental in cleaner management of DIF-contaminated soil. This study can promote the sustainable development of agriculture.

CAS / MDL: 64-19-7 10043-52-4
研究领域: 环境科学 · 微生物学 · 农业科学
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Toxics · 2022 ·Vol. 10 ·期 1 ·34 · IF 4.472

Sub-Chronic Difenoconazole Exposure Induced Gut Microbiota Dysbiosis in Mice

Zhiwei Bao,Weitao Wang,Xiaofang Wang,Mingrong Qian,Yuanxiang Jin

Difenoconazole (DIF) is a widely separated triazole fungicide in many countries. The excessive usage of DIF increases the high volume of residues in agriculture production and water bodies. Some previous studies demonstrated the toxic effects of DIF on non-target animals, however, there were still some gaps in the knowledge of the potential hazards of DIF to mammals and human health. Herein, 7-week-old male mice were exposed to 30 and 100 mg/kg/day DIF for 14 and 56 days. We observed that 56 days of DIF exposure decreased the colonic mucus expression of alcin blue-periodic acid-schiff (AB-PAS) stain and the immunochemical stain ofmuc2protein. The transcript levels of mucin protein (muc1,muc2andmuc3) decreased significantly in the gut of mice followed 56 days of 100 mg/kg/day DIF exposure. In addition, the gut microbiota composition was also affected after 14 or 56 days of DIF exposure. Although the mucus expression after 14 days of DIF exposure only decreased slightly, the gut microbiota composition compared with the control group was changed significantly. Moreover, the DIF-30 and DIF-100 caused respectively different changes on the gut microbiota. The relative abundance of Bacteroidetes decreased significantly after 14 days and 56 days of DIF exposure. After 14 days of DIF exposure, there were 35 and 18 differential genera in the DIF-30 and DIF-100 group, respectively. There were 25 and 32 differential genera in the DIF-30 and DIF-100 group after 56 days of exposure, respectively. Meanwhile, the alpha diversity indexes, including observed species, Shannon, Simpson, Chao1 and ACE, in gut microbiota decreased significantly after 56 days of DIF exposure. Interestingly, the relative abundance ofAkkermansiaincreased significantly after 56 days of 100 mg/kg/d DIF exposure. AlthoughAkkermansiawas considered as one probiotic, the phenomenon of dramaticAkkermansiaincrease with the decrease in gut microbiota diversity needed further discussion. These results provided some new insights on how DIF exposure impacts the mucus barrier and induces gut microbiota dysbiosis.Keywords:fungicides;Difenoconazole;gut microbiota;mice

研究领域: 毒理学 · 微生物学
✓ 已验证 DOI PubMed 高影响因子
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Toxics · 2023 ·Vol. 11 ·期 4 ·328 · IF 4.6

Difenoconazole Exposure Induces Retinoic Acid Signaling Dysregulation and Testicular Injury in Mice Testes

Xiangqin Zheng,Yuexin Wei,Jiadong Chen,Xia Wang,Dinggang Li,Chengjun Yu,Yifan Hong,Lianju Shen,Chunlan Long,Guanghui Wei,Shengde Wu

Difenoconazole (DFZ) is a broad-spectrum triazole fungicide that is widely utilized in agriculture. Although DFZ has been demonstrated to induce reproductive toxicity in aquatic species, its toxic effects on the mammalian reproductive system have yet to be fully elucidated. In vivo, male mice were administered 0, 20 or 40 mg/kg/d of DFZ via oral gavage for 35 days. Consequently, DFZ significantly decreased testicular organ coefficient, sperm count and testosterone levels, augmented sperm malformation rates, and elicited histopathological alterations in testes. TUNEL assay showed increased apoptosis in testis. Western blotting results suggested abnormally high expression of the sperm meiosis-associated proteins STRA8 and SCP3. The concentrations of retinoic acid (RA), retinaldehyde (RE), and retinol (ROL) were increased in the testicular tissues of DFZ-treated groups. The mRNA expression level of genes implicated in RA synthesis significantly increased while genes involved in RA catabolism significantly decreased. In vitro, DFZ reduced cell viability and increased RA, RE, and ROL levels in GC-2 cells. Transcriptome analysis revealed a significant enrichment of numerous terms associated with the RA pathway and apoptosis. The qPCR experiment verified the transcriptome results. In conclusion, our results indicate that DFZ exposure can disrupt RA signaling pathway homeostasis, and induce testicular injury in mice testes.Keywords:difenoconazole;reproductive toxicity;testis;retinoic acid signaling;GC-2 cell;apoptosis

研究领域: 毒理学 · 生殖生物学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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ChemistrySelect · 2025 ·Vol. 10 ·期 22 ·e00214 · IF 2

Fabrication and Characterization of Difenoconazole/Methyl-beta-cyclodextrin Inclusion Complexes Nanofibers by Electrospinning

Ruichi Wang,Yu Zhang,Hongwei Ji,Zechao Wei,Haoru Zhang,Fengrui Li,Shuang Gao,Ying Fu,Fei Ye

Graphical In this study, difenoconazole (DZ) was encapsulated into methyl-beta-cyclodextrin (MβCD) to form an inclusion complex and then DZ/MβCD inclusion complex nanofibers were prepared by electrospinning. The samples were characterised and tested for thermal stability, water solubility and antifungal activity. Difenoconazole (DZ) is a triazole systemic fungicide with excellent effectiveness and low toxicity. However, its low water solubility makes it only soluble in organic solvents, and solvent residues can cause environmental pollution. Electrospinning was employed to fabricate difenoconazole/methyl-beta-cyclodextrin inclusion complexes nanofibers (DZ/M β CD-IC-NF) in this study. Fourier transform infrared spectroscopy, X-ray diffraction and nuclear magnetic resonance hydrogen spectroscopy were used to characterize the structure. Scanning electron microscopy (SEM) showed that the surface of DZ/M β CD-IC-NF was smooth and beadless. Thermogravimetric analysis studies showed that the preparation of DZ/M β CD-IC-NF enhanced the thermal stability of DZ. Specifically, the rapid dissolution experiments showed that the solubility of DZ in water increased by a factor of 3.4 due to the formation of inclusion complexes. The antimicrobial activity test showed that the antimicrobial effect of DZ/M β CD-IC-NF was 1.52 times that of pure DZ. In conclusion, DZ/M β CD-IC-NF prepared by electrospinning could improve the water solubility, thermal stability and antimicrobial activity of DZ. This promotes the development of DZ towards water-based and low-polluting, and provides an effective solution to reduce the harm of DZ to the environment and to develop green and clean pesticides, thus making a positive contribution to the concept of green agricultural development.

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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2021 · IF 5.279

Electrospun Polymer-Free Nanofibers Incorporating Hydroxypropyl-β-cyclodextrin/Difenoconazole via Supramolecular Assembly for Antifungal Activity

Shuang Gao,Jingyu Jiang,Xiaoming Li,Fei Ye,Ying Fu,Lixia Zhao

In this study, flexible and self-standing hydroxypropyl-β-cyclodextrin/difenoconazole inclusion complex (HPβCD/DZ-IC) nanofibers were prepared by polymer-free electrospinning, which exhibited potential to be a new fast-dissolving pesticide formulation. Scanning electron microscopy and optical microscopy were applied to evaluate the morphology of nanofibers, which showed that the resulting HPβCD/DZ-IC nanofibers were bead-free and uniform. In addition, the proton nuclear magnetic resonance (1H NMR) spectrum suggested a stoichiometric ratio of 1:0.9 (HPβCD/DZ). Other characterization methods, such as UV–vis absorption, fluorescence spectroscopy, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA), were applied in this study. On the one hand, UV–vis absorption, fluorescence spectroscopy, FT-IR, XRD, and TGA provided useful information for the successful formation of an inclusion complex; on the other hand, the results of TGA indicated the thermal stability of DZ was enhanced after the formation of inclusion complexes. Besides, the phase solubility test could explain the increased water solubility of the nanofibers of inclusion complexes formed by DZ and HPβCD. The results of molecular docking studies demonstrated the most favorable binding interactions when HPβCD combined with DZ. The dissolution test and the antifungal performance test exhibited the characteristics of fast dissolution and the excellent antifungal performance of HPβCD/DZ-IC nanofibers, respectively.

研究领域: 材料科学 · 药学 · 纳米技术 · 化学 · 农业科学
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ENVIRONMENTAL POLLUTION · 2023 · IF 8.9

Understanding the ecological effects of the fungicide difenoconazole on soil and Enchytraeus crypticus gut microbiome

Guoyan Qin,Qi Zhang,Ziyao Zhang,Yiling Chen,Jichao Zhu,Yaohui Yang,W.J.G.M. Peijnenburg,Haifeng Qian

Increasing knowledge of the impacts of pesticides on soil ecological communities is fundamental to a comprehensive understanding of the functional changes in the global agroecosystem industry. In this study, we examined microbial community shifts in the gut of the soil-dwelling organism Enchytraeus crypticus and functional shifts in the soil microbiome (bacteria and viruses) after 21 d of exposure to difenoconazole, one of the main fungicides in intensified agriculture. Our results demonstrated reduced body weight and increased oxidative stress levels of E. crypticus under difenoconazole treatment. Meanwhile, difenoconazole not only altered the composition and structure of the gut microbial community, but also interfered with the soil-soil fauna microecology stability by impairing the abundance of beneficial bacteria. Using soil metagenomics , we revealed that bacterial genes encoding detoxification and viruses encoding carbon cycle genes exhibited a dependent enrichment in the toxicity of pesticides via metabolism. Taken together, these findings advance the understanding of the ecotoxicological impact of residual difenoconazole on the soil-soil fauna micro-ecology, and the ecological importance of virus-encoded auxiliary metabolic genes under pesticide stress.

CAS / MDL: 119446-68-3
研究领域: 环境科学 · 微生物学 · 生态学 · 农业科学
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SCIENCE OF THE TOTAL ENVIRONMENT · 2021 · IF 7.963

Histology and multi-omic profiling reveal the mixture toxicity of tebuconazole and difenoconazole in adult zebrafish

Jinhua Jiang,Liezhong Chen,Xingang Liu,Luyan Wang,Shengan Wu,Xueping Zhao

The combination effects of triazole fungicides on aquatic organisms remain largely unknown. In current study, an integrated histological, transcriptome, metabonomics and microbiology was applied to investigate the mixture effects and risk of tebuconazole (TEB) and difenoconazole (DIF) co-exposure on zebrafish liver and gonad at aquatic life benchmark. TEB and DIF mixture showed additive effect on the acute toxicity to adult zebrafish, the combined toxicity on liver was less than the additive effect of individual TEB and DIF, and TEB and DIF mixture also reduced the toxic effects on gonad and intestinal microflora. Transcriptomics and metabolomics further showed TEB and DIF mixture could induce more differentially expressed genes (DEGs) to regulate the metabolic pathways involved in energy metabolism, steroid hormone biosynthesis, retinol metabolism and microbial metabolism, to balance the energy metabolism and supplies, and maintain the steroid hormone and RA level, further reduced the toxic effect on liver and gonad caused by TEB and DIF. Our results showed the different responses and patterns on transcriptional and metabolic profiles mediated in the diverse toxicity and combination effects of TEB and DIF. The present results provided a deep mechanistic understanding of the combined effects and mode of action of DIF and TEB mixture on aquatic organisms, suggesting the concept of additive effects might sufficiently protective when evaluated the combination effects and ecological risk of TEB and DIF at aquatic life benchmarks.

CAS / MDL: 67-68-5
研究领域: 生态毒理学 · 分子生物学 · 环境科学 · 基因组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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