Behavioral and developmental toxicity assessment of the strobilurin fungicide fenamidone in zebrafish embryos/larvae (Danio rerio).

Strobilurin fungicides are among the most widely used in the world and have characteristics that include high water solubility and toxicity to aquatic organisms. While several studies report on mechanisms of toxicity of strobilurins in fish, there are no data on the sub-lethal toxicity of fish to the fungicide fenamidone. To address this gap, survival and hatch rate, deformities, mitochondrial bioenergetics, expression of oxidative stress and apoptotic genes, and behavior (locomotor activity and anxiolytic-related behaviors) were assessed in zebrafish embryos and larvae following exposure to fenamidone. Fenamidone negatively affected development of zebrafish embryos, causing a delay of hatching time at concentrations of 2.5 and 5 µM. Fenamidone caused morphological deformities in zebrafish, including pericardial edema, yolk sac edema, tail deformities, and spinal curvature. Exposure to 1.5 µM fenamidone reduced surface area of swim bladder in larvae at 6 dpf. Fenamidone significantly reduced oxygen consumption rates of embryos; 5 µM fenamidone decreased basal respiration (~85%), oligomycin induced ATP-linked respiration (~70%), FCCP-induced maximal respiration (~75%) and non-mitochondrial respiration (~90%) compared to controls. Sod2 mRNA levels were decreased by fenamidone in larval fish. Locomotor activity was significantly decreased in zebrafish larvae following exposure to 2 µM fenamidone but there was no evidence for anxiolytic nor anxiety-related behaviors (exposures of 100 nM up to 1.5 µM). This study addresses a data gap for potential risks associated with fenamidone exposure in developing fish.

Analytical method validation, dissipation and safety evaluation of combination fungicides fenamidone + mancozeb and iprovalicarb + propineb in/on tomato.

Dissipation behavior and degradation kinetics of fenamidone + mancozeb (Sectin 60 WG) and iprovalicarb + propineb (Melody Duo 66.75 WP) in tomato were studied at recommended dose (RD) and double dose (DD) of application. The analysis of the field samples were carried out by employing liquid chromatography tandem mass spectrometry (LC-MS/MS) for fenamidone and iprovalicarb residues and gas chromatography mass spectrometry for mancozeb and propineb residues after thorough validation of the extraction methods. The dissipation of residues best followed 1st + 1st order for all the test fungicides. The half-life period for fenamidone, mancozeb, iprovalicarb and propineb were 2, 2, 1.5 and 2 days for RD and 3, 2.5, 2 and 3 days for DD, respectively. The pre-harvest intervals were not applicable for iprovalicarb, fenamidone and mancozeb (at RD) as the residues at 0 day were below maximum residue limit set by European Union, and it was 1 day for DD of iprovalicarb, 3.5 days for DD of fenamidone, 3 days for DD of mancozeb, 3 and 7 days for propineb at RD and DD, respectively. A PHI of 4 and 7 days are proposed for fenamidone + Mancozeb and iprovalicarb + propineb, respectively. Dietary exposure calculated for all the pesticides were safe on all the sampling days except for propineb residues for which it was safe after first day of the double dose application. The study will be useful for promoting effective residue management and safe use of these chemicals for controlling fungal diseases in tomato crop.

Physical-Chemical Properties of the Chiral Fungicide Fenamidone and Strategies for Enantioselective Crystallization.

Thermodynamic and kinetic parameters are of prime importance for designing crystallization processes. In this article, Preferential Crystallization, as a special approach to carry out enantioselective crystallization, is described to resolve the enantiomers of the chiral fungicide fenamidone. In preliminary investigations the melting behavior and solid-liquid equilibria in the presence of solvents were quantified. The analyses revealed a stable solid phase behavior of fenamidone in the applied solvents. Based on the results obtained, a two-step crystallization route was designed and realized capable of providing highly pure enantiomers. An initial Preferential Crystallization of the racemate was performed prior to crystallizing the target enantiomer preferentially out of the enriched mother liquor. Chirality 28:514-520, 2016. © 2016 Wiley Periodicals, Inc.

Core-shell structure DA-CDs/AuNPs for the recognition of fenamidone by surface-enhanced Raman scattering.

In this work, a facile synthesis method for dopamine carbon dots-based Au nanoparticles (DA-CDs/AuNPs) by seed gold method was reported as the surface enhanced Raman scattering (SERS) booster. DA-CDs with rich in surface functional groups was synthesized using dopamine, citric acid and ethylenediamine as precursors by a facile hydrothermal method, and can be used as the capping agents and reducing agents for the synthesis of DA-CDs/AuNPs. Due to the electromagnetic "hot spots" effect, DA-CDs/AuNPs with core-shell structure exhibited strong SERS activity. Based on the specific interaction of DA-CDs/AuNPs and fenamidone, a detection method of fenamidone was established with a low detection limit of 0.05 µg/mL. Finally, the SERS sensor was successfully applied to the detection of fenamidone in fruit with recoveries between 90.6 % and 98.7 %. The method here proposed can be reliably applied for fenamidone detection on fruits.

Dynamics and residues of mixed formulation of fenamidone and mancozeb in gherkin field ecosystem.

The dynamics and residues of mixed formulation of fenamidone and mancozeb in a gherkin field ecosystem were investigated. The quantification was performed using gas chromatography-electron capture detection (GC-ECD) and UV-vis spectrophotometry for fenamidone and mancozeb residues, respectively. The method was validated using blank samples spiked at three levels and the results showed that recoveries ranged from 92 to 98 and 90 to 96 percent with relative standard deviations (RSD) ranging of 0.78-5.9 and 2.04-4.41 percent for fenamidone and mancozeb, respectively. The compound degradation followed a first order kinetics with half-lives of 2.8-2.82 and 2.02-2.26 days, for fenamidone and mancozeb, respectively. Pesticide residues in fruit were below the EU maximum residue level (MRL) after 10 days for fenamidone (0.02 µg/g) and just after treatment for mancozeb (2 µg/g). These results can be utilized in formulating the spray schedule and safety evaluation for these pesticides in gherkin.

Dissipation kinetic studies of fenamidone and propamocarb in vegetables under greenhouse conditions using liquid and gas chromatography coupled to high-resolution mass spectrometry.

In this study, fenamidone, propamocarb and their transformation products were monitored in cherry tomato, cucumber, and courgette samples. A mixture of both compounds, which have different physico-chemical characteristics, are commercially available (Consento®). For analysis, ultra high-performance liquid chromatography coupled to Orbitrap mass spectrometry (UHPLC-Orbitrap-MS) and gas chromatography coupled to Q-Orbitrap mass spectrometry (GC-Q-Orbitrap-MS) were used. The dissipation of these active ingredients was monitored at two doses (normal and double dose) from 1 to 40 days after the application of the commercial product. Half-lives (DT50) were lower than 30 days for both compounds, which indicates low persistence. Metabolites of both compounds were also monitored due to in some cases these can be more dangerous for human health than the parent compounds. The metabolites monitored were RPA 410193 ((5S)-3-anilino-5-methyl-5-phenylimidazolidine-2,4-dione), acetophenone, 2-phenylpropionic acid, 5-methyl-5-phenylhydantoin and 5-methylhydantoin for fenamidone, and propamocarb hydrochloride (propyl 3-(dimethylamino)propylcarbamate hydrochloride), N-oxide propamocarb (propyl [3-(dimethylnitroryl)propyl]carbamate), oxazoline-2-one propamocarb (3-[3-(dimethylamino)propyl]-4-hydroxy-4-methyl-1,3-oxazolidin-2-one), 2-hydroxypropamocarb and n-desmethyl propamocarb (propyl [3-(methylamino)propyl]carbamate) for propamocarb. In addition, they were detected one day after the application of commercial product, being RPA 410193, the metabolite detected at the highest concentration in samples. Retrospective analysis of incurred samples allowed putative identification of four possible new metabolites of propamocarb and one of fenamidone.