| Reference | [1]. J Biochem Mol Toxicol. 2020 Apr;34(4):e22459. doi: 10.1002/jbt.22459. Epub 2020 Jan 31.<br />
Interactions between cyazofamid and human drug transporters.<br />
Song IS(1), Jeong HU(2), Choi MK(3), Kwon M(1), Shin Y(2), Kim JH(4), Lee HS(2).<br />
Author information: (1)College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea. (2)Drug Metabolism & Bioanalysis Laboratory, College of Pharmacy, The Catholic University of Korea, Bucheon, Republic of Korea. (3)College of Pharmacy, Dankook University, Cheon-an, Republic of Korea. (4)Pesticide Chemistry and Toxicology Laboratory, Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.<br />
We aimed to investigate the intestinal permeability and interaction of cyazofamid with clinically important transporters. The intestinal permeability of cyazofamid was low (0.21 ± 0.02 cm/s), and it is a substrate for P-glycoprotein (P-gp) with a Km value of 83.1 μM, indicated that P-gp in the intestinal lumen could serve as a protective barrier to this fungicide. Cyazofamid was not a substrate for clinically important transporters. However, cyazofamid inhibited organic cation transporter 3 (OCT3) and OAT1, with IC50 values of 1.54 and 17.3 μM, respectively, but could not result in OAT3- and OAT1-mediated cyazofamid-drug interactions because of its low plasma concentration. Cyazofamid poorly interacted with OCT1, OCT2, organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, P-gp, breast cancer resistance-related protein, and multidrug resistance-related protein 2. In conclusion, the interactions of cyazofamid with human drug transporters have been evaluated as part of the safety assessment. Given its low intestinal permeability and poor interaction with human drug transporters, cyazofamid might not cause serious toxicity or adverse events.<br />
DOI: 10.1002/jbt.22459 PMID: 32003934<br />
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[2]. Molecules. 2020 Feb 11;25(4):777. doi: 10.3390/molecules25040777.<br />
The Dissipation of Cyazofamid and Its Main Metabolite CCIM During Wine-Making Process.<br />
Yang Q(1), Wei S(1), Liu N(2), Gu Z(1).<br />
Author information: (1)Department of Pesticide Science, Plant Protection College, Shenyang Agricultural University, Shenyang 110866, Liaoning, China. (2)State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.<br />
Few studies have focused on the residues of cyazofamid and its main metabolite CCIM (4-chloro-5-p-tolylimidazole-2-carbonitrile) in the wine making process, which is crucial to evaluate the potential food risk of cyazofamid and CCIM. In this work, detailed study has been conducted on the evaluation of the fate of cyazofamid and its main metabolite CCIM during the wine-making process. The targeted compounds cyazofamid and CCIM were separated and determined by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) and processing procedure including washing, peeling, fermentation, and clarification. Results showed that residues of cyazofamid and CCIM decreased significantly in wine processing. The dissipation of cyazofamid in the fermentation process followed the first-order of kinetics, and the half-life of cyazofamid was 46.2-63.0 h, whereas, the residues of CCIM, in the three treatments, decreased with time elapse. The processing factors (PFs) were all less than one in different processing processes, and the PFs ranges of cyazofamid and CCIM were 0.003-0.025 and 0.039-0.067 in three treatments in the overall process. The outcome indicated that the whole process could significantly reduce the residues of cyazofamid and CCIM in red and white wines. The results might provide more precise risk assessments of cyazofamid in the wine-making process.<br />
DOI: 10.3390/molecules25040777 PMCID: PMC7070920 PMID: 32054034 [Indexed for MEDLINE]<br />
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[3]. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2019 Sep;36(9):1327-1336. doi: 10.1080/19440049.2019.1626999. Epub 2019 Jun 21.<br />
The dissipation of cyazofamid and its main metabolite CCIM during tomato growth and tomato paste making process.<br />
Yang Q(1), Liu N(2), Zhang S(1), Wang W(1), Zou Y(1), Gu Z(1).<br />
Author information: (1)College of Plant Protection, Shenyang Agricultural University , Shenyang , P. R. China. (2)State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences , Beijing , P. R. China.<br />
In several studies focused on the residues of cyazofamid and its main metabolite 4-chloro-5-p-tolylimidazole-2-carbonitrile (CCIM) on tomato where it is widely used, CCIM has been shown to have higher acute toxicity than cyazofamid, and this is crucial to evaluate the potential food risk of cyazofamid and CCIM. In this study, the dissipation of cyazofamid and CCIM during tomato growth and tomato paste making process were assessed. The targeted compounds cyazofamid and CCIM were determined by LC-MS/MS. The results indicated that the half-life of cyazofamid was 4.6 days after applying in the field, and the maximum value of CCIM was 0.08 mg/kg at 3 days after the last application of cyazofamid, then gradually decreased. In addition, the concentrations of cyazofamid and CCIM were affected by different processing steps including washing, peeling, homogenisation, simmering, and sterilisation. Results showed that the mean losses of cyazofamid and CCIM were 92.3% and 75.2% after washing and peeling. The Processing Factor (PF) values were all less than 1. Especially for peeling, the PFs of cyazofamid and CCIM were 0.12 and 0.04, respectively.<br />
DOI: 10.1080/19440049.2019.1626999 PMID: 31226007<br />
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[4]. Chemosphere. 2019 Mar;218:26-35. doi: 10.1016/j.chemosphere.2018.11.094. Epub 2018 Nov 15.<br />
The dissipation of cyazofamid and its main metabolite in soil response oppositely to biochar application.<br />
Tang F(1), Xu Z(2), Gao M(1), Li L(3), Li H(4), Cheng H(5), Zhang C(6), Tian G(1).<br />
Author information: (1)Department of Environmental Engineering, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058, China. (2)Institute of Quality and Standard of Agro-Products, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China. Electronic address: [email protected]. (3)Department of Chemistry, School of Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, China. (4)Institute of Environment, Resource, Soil and Fertilizer, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China. (5)Department of Environmental Engineering, College of Chemical and Material Engineering, Quzhou University, Quzhou, 324000, China. (6)Institute of Quality and Standard of Agro-Products, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China.<br />
Biochars derived from rice straw (RS), corn straw (CS), chicken manure (CM) and tire rubber (TR) were applied to soil to investigate their effects on the dissipation of cyazofamid and its metabolite CCIM (4-chloro-5-p-tolylimidazole-2-carbonitrile), with high acute toxicity compared to cyazofamid. The enhancement of cyazofamid dissipation followed the order of CS > RS > CM, whereas TR depressed the cyazofamid dissipation. Adsorption, hydrolysis and microbial degradation were all involved in cyazofamid dissipation. CM and CS enhanced the contribution of biodegradation to cyazofamid dissipation, which might be related with the shifted microbial community. More importantly, CCIM residual was drastically increased by 8-15 times after biochar application, regardless of biochar type. In total, this study shed light on the issue of build-up of metabolites in biochar-amended soil, especially for metabolites having higher toxicities than parent compounds, providing new insights into potential risk of biochar application for soil remediation.<br />
DOI: 10.1016/j.chemosphere.2018.11.094 PMID: 30465972 [Indexed for MEDLINE]<br />
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[5]. Bull Environ Contam Toxicol. 2014 Nov;93(5):586-90. doi: 10.1007/s00128-014-1369-4. Epub 2014 Aug 31.<br />
Analysis of cyazofamid and its metabolite in the environmental and crop samples using LC-MS/MS.<br />
Lee H(1), Kim E, Lee JH, Sung JH, Choi H, Kim JH.<br />
Author information: (1)Environmental Measurement and Analysis Center, National Institute of Environmental Research, Incheon, 404-708, Republic of Korea.<br />
A rapid and robust LC-MS/MS method for the analysis of cyazofamid and its metabolite, 4-chloro-5-p-tolylimidazole-2-carbonitrile (CCIM), in environmental samples (soil and water) and a variety of crops (apple, mandarin, Kimchi cabbage, green pepper, potato and soybean) was established in this study. Those compounds were analyzed by selected reaction monitoring with electrospray ionization (positive mode) on LC-MS/MS. Method limit of quantitations were 2 ng g(-1) (cyazofamid) and 5 ng g(-1) (CCIM) for soil/crop samples, while 0.02 ng mL(-1) (cyazofamid) and 0.05 ng mL(-1) (CCIM) were achieved for water samples. Matrix effect (%) was different depending on sample matrices. For recovery tests, soil/crop samples were treated with QuEChERS method and water samples were extracted with dichloromethane. The recoveries of target analytes in the environmental and crop samples were 80.2 %-105.1 % for cyazofamid and 75.1 %-99.1 % for CCIM (coefficients of variation; ≤16.4 %).<br />
DOI: 10.1007/s00128-014-1369-4 PMID: 25173365
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