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1.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34638750

RESUMO

Long-term use of a single fungicide increases the resistance risk and causes adverse effects on natural ecosystems. Controlled release formulations of dual fungicides with different modes of action can afford a new dimension for addressing the current issues. Based on adjustable aperture and superhigh surface area, metal-organic frameworks (MOFs) are ideal candidates as pesticide release carriers. This study used Al3+ as the metal node and 2-aminoterephthalic acid as the organic chain to prepare aluminum-based metal-organic framework material (NH2-Al-MIL-101) with "cauliflower-like" structure and high surface area of 2359.0 m2/g. Fungicides of azoxystrobin (AZOX) and diniconazole (Dini) were simultaneously encapsulated into NH2-Al-MIL-101 with the loading content of 6.71% and 29.72%, respectively. Dual fungicide delivery system of AZOX@Dini@NH2-Al-MIL-101 demonstrated sustained and pH responsive release profiles. When the maximum cumulative release rate of AZOX and Dini both reached about 90%, the release time was 46 and 136 h, respectively. Furthermore, EC50 values as well as the percentage of inhibition revealed that AZOX@Dini@NH2-Al-MIL-101 had enhanced germicidal efficacy against rice sheath blight (Rhizoctonia solani), evidenced by the synergistic ratio of 1.83. The present study demonstrates a potential application prospect in sustainable plant protection through co-delivery fungicides with MOFs as a platform.


Assuntos
Fungicidas Industriais , Estruturas Metalorgânicas , Pirimidinas , Rhizoctonia/crescimento & desenvolvimento , Estrobilurinas , Triazóis , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/farmacocinética , Fungicidas Industriais/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacocinética , Estruturas Metalorgânicas/farmacologia , Oryza/microbiologia , Doenças das Plantas/microbiologia , Pirimidinas/química , Pirimidinas/farmacocinética , Pirimidinas/farmacologia , Estrobilurinas/química , Estrobilurinas/farmacocinética , Estrobilurinas/farmacologia , Triazóis/química , Triazóis/farmacocinética , Triazóis/farmacologia
2.
Food Chem ; 331: 127277, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32544653

RESUMO

A novel nanocomposite poly(ethylene-co-vinyl acetate) (EVA) film with controlled in vitro release of iprodione (ID) was prepared. Chitosan (CS) was used as the reinforcement which enhances the water and oxygen permeability of films. ID loaded poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) (IPP) micelles were used as the drug carrier which endows the films with antifungal and controlled release ability. IPP micelles with spherical shape and uniform size were obtained, and the maximum encapsulation efficacy (EE) was 91.17 ± 5.03% by well controlling the feeding amount of ID. Incorporation CS could improve the oxygen and moisture permeability of films, and the maximum oxygen permeability (OP) and water vapor transmission rate (WVTR) were 477.84 ± 13.03 cc/(m2·d·0.1 MPa) and 8.60 ± 0.25 g m-2 d-1, respectively. After loading IPP micelles, the films showed an improved antifungal ability and temperature-sensitive drug release behavior, and were found to enhance the quality of grapes by pre-harvest spraying.


Assuntos
Aminoimidazol Carboxamida/análogos & derivados , Hidantoínas/farmacocinética , Nanocompostos/química , Vitis/efeitos dos fármacos , Aminoimidazol Carboxamida/administração & dosagem , Aminoimidazol Carboxamida/farmacocinética , Quitosana/química , Preparações de Ação Retardada , Portadores de Fármacos , Microbiologia de Alimentos , Fungicidas Industriais/administração & dosagem , Fungicidas Industriais/farmacocinética , Hidantoínas/administração & dosagem , Lactonas/química , Micelas , Oxigênio , Permeabilidade , Polietilenoglicóis/química , Polivinil/química , Vapor
3.
J Environ Sci Health B ; 55(5): 477-483, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32449480

RESUMO

Pyraoxystrobin is a novel strobilurin fungicide that is widely used on many crops. The high log Kow of pyraoxystrobin implies that it tends to accumulate in aquatic organisms. This study optimized the sorbents of QuEChERS (quick, easy, cheap, effective, rugged, and safe) using 13C-labelled pyraoxystrobin as the internal standard (IS). It has been established a QuEChERS-LC-MS/MS IS method to study the bioconcentration and elimination of pyraoxystrobin in zebrafish (Danio rerio). The results indicated that the method had satisfactory linearity between 0.234 and 15 µg L-1 (R2 = 0.9996). The limits of detection (LOD) and quantification (LOQ) for pyraoxystrobin were 0.01 and 0.03 µg L-1, respectively. The LOQs of the method for water and zebrafish were 0.05 µg L-1 and 0.01 mg/kg, respectively. The mean recovery of pyraoxystrobin in zebrafish and water at fortification levels of 0.01-0.3 mg kg-1 and 0.05-1.5 µg L-1 ranged from 98.31 to 105.61% and 101.87 to 108.48%, respectively, with a % RSD (relative standard deviation) of 0.94-3.57%. The bioconcentration has been evaluated. The bioconcentration factors for pyraoxystrobin in zebrafish were 1,792 and 3,505 after exposure to 0.5 µg L-1 for 168 h and 0.05 µg L-1 for 216 h, respectively. The half-life of pyraoxystrobin in zebrafish was 9.0-9.5 d.


Assuntos
Acrilatos/análise , Acrilatos/farmacocinética , Fracionamento Químico/métodos , Pirazóis/análise , Pirazóis/farmacocinética , Peixe-Zebra , Acrilatos/toxicidade , Animais , Bioacumulação , Cromatografia Líquida , Ecotoxicologia/métodos , Fungicidas Industriais/análise , Fungicidas Industriais/farmacocinética , Fungicidas Industriais/toxicidade , Meia-Vida , Limite de Detecção , Pirazóis/toxicidade , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodos , Testes de Toxicidade Aguda , Poluentes Químicos da Água/análise
4.
Int J Mol Sci ; 21(8)2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32316699

RESUMO

Rutaceae are widely used in ethnomedicine to treat infectious diseases in humans and plants. In this study, the antifungal activity of the Vepris macrophylla leaf essential oil (VEO) and its main components, citral and citronellol, was evaluated against six phytopathogenic fungi. In addition, the possible action of VEO on the synthesis of mycotoxins was evaluated as well. To determine the antifungal activity of VEO we used the agar dilution method and VEO showed inhibitory activity against all the tested fungi. In particular, VEO resulted to be fungicidal against Phytophthora cryptogea and Fusarium avenaceum. For all other fungi VEO exhibited fungistatic activity and the weakest effect was observed on Alternaria solani. Citral was very effective against P. cryptogea, F. avenaceum, F. poae and F. graminearum. On the other hand, citronellol showed good activity towards P. cryptogea and F. avenaceum and weaker activity towards F. poae and F. graminearum. It can be concluded that VEO can be considered a promising antifungal agent, especially against P. cryptogea and F. avenaceum, suggesting a possible use in the formulation of new selective and natural fungicides.


Assuntos
Fungos/crescimento & desenvolvimento , Fungicidas Industriais/farmacocinética , Micotoxinas/metabolismo , Óleos Voláteis/farmacologia , Rutaceae/química , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/farmacologia , Alternaria/efeitos dos fármacos , Alternaria/crescimento & desenvolvimento , Contagem de Colônia Microbiana , Fungos/classificação , Fungos/efeitos dos fármacos , Fungicidas Industriais/química , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Óleos Voláteis/química , Phytophthora/efeitos dos fármacos , Phytophthora/crescimento & desenvolvimento , Folhas de Planta/química , Óleos de Plantas/química , Óleos de Plantas/farmacologia
5.
Biomed Chromatogr ; 34(7): e4836, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32222076

RESUMO

The dissipation dynamic and residues of spiroxamine in open-field-grown strawberries were determined using liquid chromatography tandem mass spectrometry (LC-MS/MS). Spiroxamine application was performed according to Egyptian good agricultural practices recommendation. A QuEChERS-based extraction method along with direct analysis with an LC-MS/MS analytical method were optimized and validated, and the specificity of the techniques used was considered satisfactory. Good linearity (R2 > 0.999) was obtained for spiroxamine within the range of 0.001-0.1 µg/ml. The mean recoveries varied between 97.1 and 108.2%, with inter- and intra-day precision (RSD) <4.9%. The limit of quantitation for spiroxamine was 0.001 mg/kg. The results indicated that spiroxamine degradation in strawberry followed first-order kinetics (R2 > 0.9929) with an estimated half-life value of 4.71 days. Considering the Australian maximum residue limit (0.05 mg/kg) in strawberry and based on the results from residue trials with a preharvest interval of 14 days for strawberry, compliance can be expected. The present results could provide guidance to fully evaluate the risks of spiroxamine residues, preventing any potential health risk to consumers.


Assuntos
Cromatografia Líquida/métodos , Fragaria , Fungicidas Industriais/análise , Resíduos de Praguicidas/análise , Compostos de Espiro/análise , Egito , Inocuidade dos Alimentos , Fragaria/química , Fragaria/metabolismo , Fungicidas Industriais/farmacocinética , Modelos Lineares , Resíduos de Praguicidas/farmacocinética , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e Especificidade , Compostos de Espiro/farmacocinética , Espectrometria de Massas em Tandem/métodos
6.
Chem Res Toxicol ; 33(6): 1449-1457, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32154713

RESUMO

Over 30% of commercial pesticides are racemic mixtures. Nowadays, the environmental safety of chiral pesticides has received more and more attention. Metalaxyl is a broad-spectrum fungicide with systemic function, which has a chiral carbon. Although its fungicidal activity almost entirely originates from the R-enantiomer, the enantioselective toxicity of metalaxyl in animals and human beings are not yet clear. In this study, the urinary metabolomics approach was applied to analyze the changes in metabolic phenotypes in adolescent rats by using nuclear magnetic resonance (NMR). In the urinary metabolomics results, the metabolic profiles of the different enantiomers were distinguishable, and the characteristic metabolites were different. Both in the exposure of R/S-enantiomers, the disturbed metabolic pathways in common were butanoate metabolism, valine, leucine and isoleucine biosynthesis, alanine, aspartate and glutamate metabolism, and glutamine and glutamate metabolism. These pathways were closely involved in gut microbiota. In addition to the disturbed metabolic pathways common to both, three metabolic pathways were abnormal in the exposure of S-metalaxyl, including aminoacyl-tRNA biosynthesis, arginine biosynthesis, and citrate cycle. These disturbed metabolic pathways could cause genetic diseases and affect the liver function. These results indicate that a specific insight into the effects of different metalaxyl enantiomers on metabolic disturbance. Our work could allow us to well understand the health risk assessments of metalaxyl enantiomers, especially at the metabolic level.


Assuntos
Alanina/análogos & derivados , Fungicidas Industriais/farmacocinética , Metaboloma/efeitos dos fármacos , Alanina/química , Alanina/farmacocinética , Alanina/urina , Animais , Feminino , Fungicidas Industriais/química , Fungicidas Industriais/urina , Metabolômica , Fenótipo , Espectroscopia de Prótons por Ressonância Magnética , Ratos Sprague-Dawley , Estereoisomerismo
7.
J Biochem Mol Toxicol ; 34(4): e22459, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32003934

RESUMO

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.


Assuntos
Permeabilidade da Membrana Celular , Fungicidas Industriais/metabolismo , Fungicidas Industriais/farmacologia , Imidazóis/metabolismo , Imidazóis/farmacologia , Proteínas de Membrana Transportadoras/metabolismo , Sulfonamidas/metabolismo , Sulfonamidas/farmacologia , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Transporte Biológico , Células CACO-2 , Interações Medicamentosas , Fungicidas Industriais/farmacocinética , Células HEK293 , Humanos , Imidazóis/farmacocinética , Concentração Inibidora 50 , Intestinos/fisiologia , Células LLC-PK1 , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Transportadores de Ânions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Sulfonamidas/farmacocinética , Suínos
8.
Biomed Chromatogr ; 34(3): e4745, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31725903

RESUMO

Using LC-MS/MS, a rapid and sensitive method for the simultaneous determination of pyraclostrobin and azoxystrobin residues in banana matrices (leaf and whole banana) and soil was established. The samples were extracted using acetonitrile and purified through C18 dispersive solid-phase extraction. The average recovery of the analytes in various matrices was in the range of 77.3%-103.9% with an RSD range of 0.9%-9.5%. The initial deposition amounts of pyraclostrobin and azoxystrobin at 2 h in the banana leaves of the mineral oil group were 1.43 and 1.31 times in Guangxi, and 2.10 and 1.81 times in Hainan for the water group, whereas those in the soil of the water group were 3.45 and 3.03 times in Guangxi, and 2.14 and 3.48 times in Hainan for the mineral oil group. The half-lives in the leaves and soil of the mineral oil group were not remarkably different from those of the water group. The terminal residue of the analytes on the whole banana was <0.02 mg/kg at 14 days after application from the two sites. The results of this work may indicate and promote the safety of using pyraclostrobin and azoxystrobin in banana production, especially with mineral oil spray adjuvants.


Assuntos
Óleo Mineral/química , Musa/química , Resíduos de Praguicidas , Pirimidinas , Estrobilurinas , Cromatografia Líquida/métodos , Frutas/química , Fungicidas Industriais/análise , Fungicidas Industriais/isolamento & purificação , Fungicidas Industriais/farmacocinética , Cinética , Limite de Detecção , Modelos Lineares , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/isolamento & purificação , Resíduos de Praguicidas/farmacocinética , Folhas de Planta/química , Pirimidinas/análise , Pirimidinas/isolamento & purificação , Pirimidinas/farmacocinética , Reprodutibilidade dos Testes , Solo/química , Extração em Fase Sólida , Estrobilurinas/análise , Estrobilurinas/isolamento & purificação , Estrobilurinas/farmacocinética , Espectrometria de Massas em Tandem/métodos
9.
Environ Geochem Health ; 42(1): 109-120, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31037581

RESUMO

Nowadays, nanocarbon is widely employed to enwrap into fertilizers. However, the influence of nanocarbon on the transportation of contaminants from soil to plants and its mechanism remain unclear. In this study, pentachloronitrobenzene (PCNB), a typical organochlorine fungicide utilized all over the world, was chosen as the target contaminant to investigate the influence of nanocarbon on its transportation in soil-pak choi system. The maximum PCNB concentration in the root and leaf reached to 112 and 86 ng/g, respectively, demonstrating that PCNB would be absorbed by pak choi. The ratio of PCNB between leaf and root indicated that nanocarbon promoted root of pak choi to absorb PCNB. The transportation of PCNB inside plant was inhibited when pak choi was planted in soil containing higher concentration of nanocarbon. Human risk assessment showed that people consuming the pak choi in this study would not experience risk. However, in vitro toxicity test indicated that PCNB could directly impair intestinal epithelial cells (Caco-2 cells) and thus pose a potential risk to human intestine.


Assuntos
Brassica/metabolismo , Fertilizantes , Nitrobenzenos/farmacocinética , Nitrobenzenos/toxicidade , Poluentes do Solo/farmacocinética , Transporte Biológico , Brassica/química , Células CACO-2 , Exposição Dietética , Contaminação de Alimentos , Fungicidas Industriais/farmacocinética , Fungicidas Industriais/toxicidade , Humanos , Nanoestruturas , Folhas de Planta/química , Folhas de Planta/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Medição de Risco , Solo/química , Poluentes do Solo/toxicidade , Testes de Toxicidade Aguda
10.
J Environ Sci Health B ; 55(3): 175-183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31631749

RESUMO

The purpose of this study was to study the excretion stereoselectivity of triticonazole enantiomers in rat urine and faeces. Six male Sprague-Dawley (SD) rats were administrated 50 mg/kg rac-triticonazole. Rats urine and faeces were separately and quantitatively collected at the following intervals: 0-3, 3-6, 6-9, 9-12, 12-24, 24-36 and 36-48 h. The faeces samples were homogenized in an aqueous solution containing 0.2% DMSO at the ratio of 1 g: 40 mL. An aliquot of 100 µL rats urine or faeces homogenate was spiked and mixed with 6.0 µL of 1.00 µg/mL flusilazole as an internal standard. The triticonazole enantiomers in urine and faeces were determined by using an HPLC/MS-MS after samples preparation. The excreted amounts of enantiomers in the urine showed a significant difference (P < 0.05) except for 3-6 h. The cumulative excretion rate (Xu0→24) in urine was 26.43 ± 0.08% and 37.58 ± 0.11% for R-(-)- and S-(+)-triticonazole, respectively, indicating high enantioselectivity (P < 0.001). The cumulative excretion rate (Xu0→72) in faeces was 6.93 ± 0.03% and 6.77 ± 0.03% for R-(-)- and S-(+)-triticonazole, respectively, without a difference. The results showed that the total cumulative percentage of triticonazole enantiomers accounted for in urine and faeces was 64.00 ± 0.13% and 13.70 ± 0.32%, the urinary excretion of R-(-)- and S-(+)-triticonazole were significantly different and S-(+)-triticonazole was preferentially excreted. However, the faecal excretion of the enantiomers showed no difference.


Assuntos
Ciclopentanos/química , Ciclopentanos/farmacocinética , Fezes/química , Triazóis/química , Triazóis/farmacocinética , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão/métodos , Ciclopentanos/urina , Fungicidas Industriais/química , Fungicidas Industriais/farmacocinética , Fungicidas Industriais/urina , Masculino , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Silanos/urina , Estereoisomerismo , Espectrometria de Massas em Tandem , Triazóis/urina
11.
J Environ Sci Health B ; 55(4): 388-395, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31868560

RESUMO

To stipulate the rationale of spraying doses and to determine the safe interval period of boscalid suspension concentrate (SC), the degradation dynamics and residual levels were investigated in cucumber and soil using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Field trials were conducted according to Chinese Guideline on pesticide residue trials. Following application, the degradation kinetics was best ascribed to first-order kinetic models with half-life of 2.67-9.90 d in cucumber. Spraying boscalid SC at 1.5-fold the recommended dosage yield terminal residues, which are clearly lower than the maximum residue limit (MRL) established by China (MRL =5 mg.kg-1) in cucumber. At variance, the dissipation dynamics in soil did not fit to first-order kinetics and the half-life was more than 17 days, the finding which denotes that the degradation behavior of boscalid in soil proceeds slowly. It has therefore been shown that boscalid is safe for use on cucumbers under the recommended dosage.


Assuntos
Compostos de Bifenilo/análise , Cucumis sativus/química , Niacinamida/análogos & derivados , Resíduos de Praguicidas/análise , Poluentes do Solo/análise , Compostos de Bifenilo/farmacocinética , China , Cromatografia Líquida/métodos , Contaminação de Alimentos/análise , Fungicidas Industriais/análise , Fungicidas Industriais/farmacocinética , Niacinamida/análise , Niacinamida/farmacocinética , Poluentes do Solo/farmacocinética , Espectrometria de Massas em Tandem/métodos
12.
Regul Toxicol Pharmacol ; 108: 104438, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31461669

RESUMO

Herein, we publish data from regulatory studies investigating the oral ADME (absorption, distribution, metabolism, excretion) of tricyclazole in vivo, in silico and in vitro. The oral route is relevant to human dietary exposure assessment. Tricyclazole is readily absorbed and highly bioavailable in rodents (>86%) with indication of saturation of absorption at high doses. Enterohepatic recirculation is evident. Excretion occurs quickly both via urinary (31-64%) and faecal routes (39-65%), with substantial biliary elimination in the rat (≥58%). The tricyclazole-derived radioactivity is distributed to major organs, including those investigated in in vivo genotoxicity studies (liver, kidney, gastrointestinal tract and bone marrow). There is no evidence of bioaccumulation. Metabolism is extensive (approximately 30 metabolites), with the liver being identified as the primary metabolism organ with Phase I and II enzymes involved. Several metabolites are formed following an initial cleavage of the central thiazole ring, with no loss of free triazole from the remaining phenyl ring. A group of 4 metabolites derive from an initial oxidation step with the formation of the tricyclazole-alcohol, a relevant crop metabolite, and account for up to 13% of the administered dose. In vitro metabolism, investigated with liver microsomes, confirmed that humans do not form unique metabolites.


Assuntos
Fungicidas Industriais/farmacocinética , Tiazóis/farmacocinética , Administração Oral , Animais , Humanos , Medição de Risco
13.
J Environ Sci Health B ; 54(10): 810-816, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31264918

RESUMO

Pesticides are biological or chemical substances used to manage pests and diseases. Encapsulation of pesticides in biodegradable carriers creates a slow-release system that can improve water dispersibility and prolong residual activity. We prepared two kinds of poly (lactic-co-glycolic acid)(PLGA) nanoparticles (NPs) with polyvinyl alcohol (PVA) and sodium dodecyl sulfate (SDS) surfactants. These were used to encapsulate the fungicide fluazinam (Flu) against Rhizoctonia solani using the Shirasu Porous Glass (SPG) membrane emulsification method. Both nanoparticles had uniform spherical shapes with average diameters of 314.13 nm (SDS) and 612.80 nm (PVA). The slow-release microspheres had excellent sustained-release properties, resistance to UV degradation, storage stability, leaf surface coverage and antifungal efficacy compared to the commercial formulation.


Assuntos
Aminopiridinas/farmacocinética , Fungicidas Industriais/farmacocinética , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Aminopiridinas/farmacologia , Fungicidas Industriais/farmacologia , Microesferas , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/metabolismo , Álcool de Polivinil/química , Porosidade , Rhizoctonia/efeitos dos fármacos , Dodecilsulfato de Sódio/química , Espectrofotometria Ultravioleta , Tensoativos/química
14.
Chemosphere ; 233: 183-189, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31173956

RESUMO

Tolclofos-methyl (TM) is an organophosphorus fungicide and widely utilized to control soil-borne diseases. However, toxic effects of TM on terrestrial invertebrates are still unknown. Here we measured the bioaccumulation of TM in earthworms (Eisenia fetida) to assess its environmental bioavailability. Mortality, weight change, and oxidative damage of earthworms were determined to investigate the toxicological bioavailability of TM. ROS, SOD and MDA in highest concentration treatment group significantly increased compared to the control group, suggesting that hazardous effects of TM to earthworms were caused by the oxidative stress. To further examine its toxicological bioavailability, cytotoxicity test was carried out by using extracted earthworm coelomocytes. The biomarkers, e.g., intracellular ROS, extracellular LDH, and cell viability showed correlation with TM in the culture media, demonstrating that cytotoxicity test could be employed to reflect the toxicological bioavailability of pollutants to earthworms or other organisms.


Assuntos
Ecotoxicologia/métodos , Oligoquetos/efeitos dos fármacos , Compostos Organotiofosforados/farmacocinética , Poluentes do Solo/farmacocinética , Animais , Disponibilidade Biológica , Sobrevivência Celular/efeitos dos fármacos , Biomarcadores Ambientais , Fungicidas Industriais/farmacocinética , Fungicidas Industriais/toxicidade , L-Lactato Desidrogenase/metabolismo , Malondialdeído/metabolismo , Oligoquetos/citologia , Compostos Organotiofosforados/toxicidade , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Solo/química , Superóxido Dismutase/metabolismo
15.
Ecotoxicol Environ Saf ; 181: 96-105, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31176252

RESUMO

Tebuconazole (TEB) is a chiral triazole fungicide that is globally marketed and used as a racemic mixture to control plant pathogens. Due to its use as a racemic mixture, TEB may exhibit enantioselective toxicokinetics toward nontarget organisms, including humans. Therefore, the in vitro enantioselective metabolism of TEB by cytochrome P450 enzymes (CYP450) was studied using human liver microsomes, and the in vivo toxicokinetic parameters were predicted. A new enantioselective, reversed-phase LC-MS/MS method was developed and validated to analyze the enantiomers of TEB and its main metabolite, 1-hydroxytebuconazole (TEBOH). In vitro metabolic parameters were obtained, and in vitro-in vivo extrapolations were performed. Michaelis-Menten and atypical biphasic kinetic profiles were observed with a total intrinsic clearance ranging from 53 to 19 mL min-1 mg-1. The in vitro-in vivo extrapolation results showed that TEB first passage effect by the liver seems to be negligible, with hepatic clearance and extraction ratios ranging from 0.53 to 5.0 mL min-1 kg-1 and 2.7-25%, respectively. Preferential metabolism of (+)-TEB to rac-TEB and (-)-TEB was observed, with preferential production of (+)-TEBOH. Furthermore, reaction phenotyping studies revealed that, despite the low hepatic clearance in the first pass metabolism of TEB, multiple human CYP450 isoforms were involved in TEB metabolism when TEBOH enantiomers were generated, mainly CYP3A4 and CYP2C9, which makes TEB accumulation in the human body more difficult due to multiple metabolic pathways.


Assuntos
Fungicidas Industriais/metabolismo , Microssomos Hepáticos/metabolismo , Triazóis/metabolismo , Cromatografia Líquida , Sistema Enzimático do Citocromo P-450/metabolismo , Fungicidas Industriais/química , Fungicidas Industriais/farmacocinética , Fungicidas Industriais/toxicidade , Humanos , Fígado/metabolismo , Estereoisomerismo , Espectrometria de Massas em Tandem , Toxicocinética , Triazóis/química , Triazóis/farmacocinética , Triazóis/toxicidade
16.
Food Chem Toxicol ; 128: 202-211, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30991128

RESUMO

Myclobutanil is a chiral triazole fungicide that is employed worldwide. Although enantiomers have the same physical-chemical properties, they may differ in terms of activity, metabolism, and toxicity. This investigation consisted of in vitro enantioselective metabolism studies that employed a human model to assess the risks of myclobutanil in humans. A LC-MS/MS enantioselective method was developed and validated. The enzymatic kinetic parameters (VMAX, KMapp, and CLINT) determined for in vitro rac-myclobutanil and S-(+)-myclobutanil metabolism revealed enantioselective differences. Furthermore, human CYP450 enzymes did not metabolize R-(-)-myclobutanil. The predicted in vivo toxicokinetic parameters indicated that S-(+)-myclobutanil may be preferentially eliminated by the liver and suffer the first-pass metabolism effect. However, because CYP450 did not metabolize R-(-)-myclobutanil, this enantiomer could reach the systemic circulation and stay longer in the human body, potentially causing toxic effects. The CYP450 isoforms CYP2C19 and CYP3A4 were involved in rac-myclobutanil and S-(+)-myclobutanil metabolism. Although there were differences in the metabolism of the myclobutanil enantiomers, in vitro inhibition studies did not show significant enantioselective differences. Overall, the present investigation suggested that myclobutanil moderately inhibits CYP2D6 and CYP2C9 in vitro and strongly inhibits CYP3A and CYP2C19 in vitro. These results provide useful scientific information for myclobutanil risk assessment in humans.


Assuntos
Inibidores das Enzimas do Citocromo P-450/toxicidade , Sistema Enzimático do Citocromo P-450/metabolismo , Fungicidas Industriais/toxicidade , Nitrilas/toxicidade , Triazóis/toxicidade , Cromatografia Líquida , Inibidores das Enzimas do Citocromo P-450/farmacocinética , Fungicidas Industriais/farmacocinética , Humanos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Nitrilas/química , Nitrilas/farmacocinética , Reprodutibilidade dos Testes , Estereoisomerismo , Espectrometria de Massas em Tandem , Toxicocinética , Triazóis/química , Triazóis/farmacocinética
17.
J Pharm Biomed Anal ; 172: 78-85, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31035096

RESUMO

Triticonazole with an asymmetrical carbon atom has two enantiomers and is a broad-spectrum systemic fungicide, but its disposition in animals is unclear. In this study, a chiral analytical method of LC-MS/MS was developed and validated for the assay of triticonazole enantiomers in rat plasma and tissues. There were no endogenous interferences in the blank plasma and tissues of rats. R-(-)- and S-(+)-triticonazole peaks were separated entirely. The calibration curves were linear from 25 to 2500 ng/mL of each enantiomer. The accuracy, precision, and stability met the requirements of bioanalysis. Therefore, this method is enantioselective, accurate, precise, sensitive and reliable, and has been successfully applied to analyze R-(-)- and S-(+)-triticonazole in rat plasma and to study the toxicokinetics of triticonazole enantiomers in rats. After single oral administration of 50 mg/kg racemate triticonazole to rats, the AUC (0-∞) and Cmax of R-(-)-triticonazole were 3.5 and 3.6 times higher than that of S-(+)-triticonazole, respectively. The content of S-(+)-triticonazole was higher in the kidney whilst R-(-)-triticonazole was higher in the brain and small intestine. The results showed that the toxicokinetics and tissues distribution of triticonazole enantiomers in rats have stereoselective differences.


Assuntos
Ciclopentanos/toxicidade , Fungicidas Industriais/toxicidade , Triazóis/toxicidade , Administração Oral , Animais , Coleta de Amostras Sanguíneas/métodos , Cromatografia Líquida de Alta Pressão , Ciclopentanos/administração & dosagem , Ciclopentanos/farmacocinética , Fungicidas Industriais/administração & dosagem , Fungicidas Industriais/farmacocinética , Masculino , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estereoisomerismo , Espectrometria de Massas em Tandem , Distribuição Tecidual , Testes de Toxicidade/métodos , Toxicocinética , Triazóis/administração & dosagem , Triazóis/farmacocinética
18.
Toxicol Sci ; 169(1): 167-179, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30768125

RESUMO

2,4,6-tribromophenol (TBP, CAS No. 118-79-6) is widely used as a brominated flame retardant and wood antifungal agent. TBP is frequently detected in environmental matrices, biota, and humans. In female SD rats, systemically available TBP (10 µmol/kg, IV) was rapidly excreted primarily via urine, with approximately 61% of the dose recovered after 4 h, and 89%-94% in 24 h; 5% was recovered in feces; and 1%-2% in blood/tissues. TBP administered to female SD rats (0.1-1000 µmol/kg) by gavage was well absorbed, with approximately 25% eliminated via urine after 4 h and approximately 88% after 24 h. Approximately 11% of a single oral dose was recovered in bile. Male SD rats and B6C3F1/J mice of both sexes had similar disposition profiles when administered a single oral dose of TBP (10 µmol/kg). Following administration, fecal recoveries varied only slightly by dose, sex, or species. TBP readily passed unchanged through both human (ex vivo only) and rat skin with between 55% and 85% of a 100 nmol/cm2 passing into or through skin. Concentrations of TBP in blood fit a two-compartment model after IV-dosing and a one-compartment model after oral dosing. Urine contained a mixture of TBP, TBP-glucuronide, and TBP-sulfate. Fecal extracts contained only parent TBP whereas bile contained only TBP-glucuronide. TBP did not appear to bioaccumulate or alter its own metabolism after repeated administration. TBP was readily absorbed at all doses and routes tested with an oral bioavailability of 23%-27%; 49% of TBP is expected to be dermally bioavailable in humans. From these data, we conclude that humans are likely to have significant systemic exposure when TBP is ingested or dermal exposure occurs.


Assuntos
Retardadores de Chama/administração & dosagem , Retardadores de Chama/farmacocinética , Fungicidas Industriais/administração & dosagem , Fungicidas Industriais/farmacocinética , Fenóis/administração & dosagem , Fenóis/farmacocinética , Administração Cutânea , Administração Oral , Animais , Bile/metabolismo , Disponibilidade Biológica , Biotransformação , Fezes/química , Feminino , Fungicidas Industriais/sangue , Fungicidas Industriais/urina , Eliminação Hepatobiliar , Humanos , Injeções Intravenosas , Eliminação Intestinal , Masculino , Camundongos , Modelos Biológicos , Fenóis/sangue , Fenóis/urina , Ratos , Ratos Sprague-Dawley , Eliminação Renal , Fatores Sexuais , Especificidade da Espécie , Distribuição Tecidual
19.
J Environ Sci Health B ; 54(3): 196-204, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30638127

RESUMO

In this study, tebuconazole (TEB)-loaded poly-3-hydroxybutyrate (P3HB)-based microparticles were developed and comprehensively characterized. TEB-loaded microparticles with the initial loading amounts of the fungicide of 10, 25, and 50% of the polymer mass (TEB 10, TEB 25, and TEB 50%) were prepared using emulsion technique. Encapsulation efficiency of TEB varied from 59 to 86%. As the loading amount was increased, the average diameter of microparticles increased too, from 41.3 to 71.7 µm, while zeta potential was not influenced by TEB loading, varying between -32.6 and -35.7 mV. TEB was gradually released from the microparticles to the model medium, and after 60 d, from 25 to 43% of TEB was released depending on the content of the encapsulated fungicide. The data obtained from in vitro TEB release were fitted to different mathematical models. It was shown that the release profiles of TEB could be best explained by the Zero-order, Higuchi, and Hixson-Crowell models. The antifungal activity of the P3HB/TEB microparticles against phytopathogenic fungi Fusarium moniliforme and Fusarium solani was demonstrated by in vitro tests conducted in Petri dishes. Thus, hydrophobic agrochemicals (TEB) can be effectively encapsulated into P3HB microparticles to construct slow-release formulations.


Assuntos
Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Fusarium/efeitos dos fármacos , Triazóis/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Emulsões/química , Fungicidas Industriais/farmacocinética , Fusarium/patogenicidade , Hidroxibutiratos/química , Modelos Teóricos , Tamanho da Partícula , Poliésteres/química , Triazóis/química
20.
Environ Sci Pollut Res Int ; 26(6): 6077-6086, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30613891

RESUMO

The present study describes the uptake and distribution of fungicides, fluopyram, and tebuconazole in tomato and bell pepper plant tissues from the soil drench application of their combination product fluopyram17.7% + tebuconazole 17.7%. For extraction and cleanup of fluopyram, its metabolite fluopyram benzamide, and tebuconazole samples, the QuEChERS method was used in conjunction with LC-MS/MS. The limit of detection (LOD) and limit of quantification (LOQ) of the method determined were 1.5 µg kg-1 and 0.005 mg kg-1, respectively, and recoveries of all analytes from sample matrices remained within the acceptable range of 70-120%. Rapid uptake of the fungicides by tomato and bell pepper plants was observed from the first day onwards. In the tomato plant, the major part of the fungicides accumulated in the roots, whereas in bell pepper plant, it accumulated both in the roots and in the leaves. Accumulation of fluopyram and tebuconazole residues was lowest in tomato and bell pepper fruits which were much below their respective maximum residue limits (MRLs). The highest residue concentration of fluopyram and tebuconazole in tomato fruits was 0.060 and 0.009 mg kg-1; the corresponding values in bell pepper fruits were 0.080 and 0.013 mg kg-1. In field soil, fluopyram residues were 3.18-3.570 mg kg-1 initially which dissipated at the half-life of 36 days. Tebuconazole concentration was 1.57-1.892 mg kg-1 initially, and it dissipated at the half-life of 44.5-49.5 days. The major metabolite of fluopyram, fluopyram benzamide, was detected in plant tissues as well as in soil, and remained within 12% of the parent compound. The results of the study indicated that fluopyram and tebuconazole are less likely of entry into food chain through intake of tomato and bell pepper fruits if these crops are grown on soil contaminated with these fungicides.


Assuntos
Benzamidas/análise , Capsicum/química , Resíduos de Praguicidas/análise , Piridinas/análise , Poluentes do Solo/análise , Solanum lycopersicum/química , Triazóis/análise , Benzamidas/farmacocinética , Cromatografia Líquida , Frutas/química , Fungicidas Industriais/análise , Fungicidas Industriais/farmacocinética , Meia-Vida , Resíduos de Praguicidas/farmacocinética , Piridinas/farmacocinética , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Triazóis/farmacocinética
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