benzofurans and ethofumesate

Ethofumesate is a chiral herbicide that may display enantioselective behavior in humans. For this reason, the enantioselective potential of ethofumesate and its main metabolite ethofumesate-2-hydroxy to cause pesticide-drug interactions on cytochrome P450 forms (CYPs) has been evaluated by using human liver microsomes. Among the evaluated CYPs, CYP2C19 had its activity decreased by the ethofumesate racemic mixture (rac-ETO), (+)-ethofumesate ((+)-ETO), and (-)-ethofumesate ((-)-ETO). CYP2C19 inhibition was not time-dependent, but a strong inhibition potential was observed for rac-ETO (IC

Topics: Benzofurans; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Dose-Response Relationship, Drug; Drug Discovery; Humans; Mesylates; Molecular Docking Simulation; Pesticides; Protein Binding; Protein Conformation; Stereoisomerism

Analytical method was developed for determining the total residue of ethofumesate (ET) herbicide using GC-MS/MS. The ET residues were analyzed as a sum of ET, 2-keto-ethofumesate (KET), and open-ring-2-keto-ethofumesate (OKET) and its conjugate. The extracted samples were partitioned with hexane and NaOH solution. For ET analysis, the hexane layer was cleaned up by a silica gel cartridge prior to GC-MS/MS analysis. For the analyses of the metabolites, the aqueous layer was heated with HCl to hydrolyze the conjugates, thereafter, heated in acetic anhydride to convert OKET to KET, and cleaned up by a silica gel cartridge prior to GC-MS/MS analysis. The method was validated for ET, KET, and OKET in garlic, onion, and sugar beet at 0.3 and 0.01 mg/kg. The recoveries were 94-113%, with relative standard deviations of <6%. The limits of detection were 0.0005 mg/kg for all analytes. The proposed method is suitable for regulatory analysis.

Topics: Benzofurans; Chromatography, High Pressure Liquid; Garlic; Gas Chromatography-Mass Spectrometry; Limit of Detection; Mesylates; Onions; Pesticide Residues; Tandem Mass Spectrometry

Topics: Benzofurans; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP3A; Herbicides; Humans; In Vitro Techniques; Mesylates; Microsomes, Liver; Reproducibility of Results; Stereoisomerism

The aim of this study was to evaluate the coupled impact of an herbicide, ethofumesate, and temperature on the cellular energy metabolism of juvenile roach, especially on the glycolysis pathway. Juvenile roach were exposed to 0, 0.5, 5, and 50 μg/L of ethofumesate for 7 days in laboratory conditions at two temperatures (10 and 17 °C). The energy reserves (carbohydrate, lipid, and protein) were quantified, since the availability of substrates regulates the glycolysis. Then, the glycolysis was studied at the biochemical level by the measurement of the glycolytic flux and at the molecular level with the measurement of the relative expression of four genes encoding for glycolysis enzymes. This study revealed different effect of ethofumesate on the glycolysis pathway according to the temperature of exposure. Indeed, at 10 °C, it appeared that only the molecular regulation level was affected, whereas, at 17 °C, ethofumesate acted on the biochemical level. The differences observed between the two exposures imply the establishment of different strategies in order to maintain to cope with stress according to the temperature of exposure.

Topics: Aerobiosis; Anaerobiosis; Animals; Benzofurans; Cyprinidae; Energy Metabolism; Glycolysis; Mesylates; Temperature; Water Pollutants, Chemical

The commercial herbicide formulation Betanal® Expert and its active ingredients (a.i.s) ethofumesate, phenmedipham and desmedipham were focused in this study. Following questions yielding from a previous study, an in-depth analysis of the reproductive toxicity of the pesticide was made. Long-term exposures of Daphnia magna and Daphnia longispina to Betanal® Expert, to each a.i. and to a customised mixture matching the a.i.s ratio within the commercial formulation were carried out, and deleterious effects in the offspring were recorded. This intended to clarify whether (1) the tested compounds induce reproductive injury; (2) there is interspecific variation in daphnids tolerance to the compounds; (3) there is an interaction between chemicals in combined treatments; and (4) the so-called inert ingredients added to the commercial formulation contribute to the toxicity of the herbicide. Generally, developmental impair was observed in both species (egg abortion and release of undeveloped embryos or dead offspring) at concentrations of any of the a.i.s below 1 mg L(-1). Ethofumesate was invariably the least toxic pesticide, and D. magna tended to be of slightly higher sensitivity to the exposures compared to D. longispina. Joint exposures indicated that the a.i.s can interact, inducing more than and less than additive effects for Betanal® Expert and the customised a.i. mixture, respectively. This indicates that inert ingredients co-formulating the commercial pesticide (which are absent from the customised a.i. mixture) actually contribute to its overall toxicity. This study constitutes an add-on to the discussion on the ecotoxicological framework required for authorisation of pesticide trade and usage. The results support the need to consider test species, long-term hazardous potential and toxicity of commercial formulations rather than solely that of active ingredients, as relevant variables in pesticide regulation.

Topics: Animals; Benzofurans; Carbamates; Daphnia; Female; Herbicides; Mesylates; Reproduction; Water Pollutants, Chemical

Herbicides are used in large amounts in agriculture and the evaluation of their toxic effects is of major concern to environmental safety. The aim of the present study was to investigate common carp hematological alterations caused by herbicide exposure. Fish were treated with pendimethalin and ethofumesate tested separately and in mixture administered to aquarium water. Peripheral blood of treated fish was collected after 1, 3 and 7 days of exposure and compared to control. The total number of erythrocytes (RBC), total number of leukocytes (WBC), hematocrit value (Hct), total hemoglobin concentration (Hb), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and leukograms were determined at once. The results indicate that herbicide exposure caused different changes in the hematological profile of the fish. In the case of exposure to individual herbicides, short-term fluctuations of various hematological indices were noted. Moreover, a significant increase in RBC and Hct after a short period of exposure (1-3 days) in fish exposed simultaneously to both tested herbicides was observed. Exposure to herbicides affected the leukocyte profile after 3 and 7 days of duration. Fluctuations of hematological parameters are a typical change in fish exposed to pesticides.

Topics: Aniline Compounds; Animals; Benzofurans; Carps; Hematologic Tests; Herbicides; Mesylates

New herbicidal formulations were designed by combining wheat gluten (WG), two montmorillonites (MMTs) (unmodified and organically modified) and a model pesticide (ethofumesate), and their performances were assessed through an integrative study conducted in soil using an experimental methodology with data modelling.. All the WG formulations tested were effective in decreasing the apparent diffusivity of ethofumesate in soil in comparison with the non-formulated active substance. The slow-release effect was significantly more pronounced in the presence of the organically modified MMT, confirming the importance of sorption mechanisms to reduce ethofumesate diffusion. The bioassays undertaken on watercress to evaluate herbicidal antigerminating performances showed that all the WG formulations (with or without MMT) were more effective than both the commercial formulation and the non-formulated ethofumesate, whatever the concentration tested. To explain such results, it was proposed that WG formulations would enable ethofumesate to be more available and thus more effective in inhibiting seed germination, as they would be less prone to be leached by water transport due to watering and also less subject to photodegradation.. The use of pesticide formulations based on wheat gluten and nanoclays appeared to be a promising strategy both to reduce the mobility of pesticides in soil and to protect UV-photosensitive pesticides from photodegradation.

Topics: Bentonite; Benzofurans; Diffusion; Glutens; Herbicides; Lepidium sativum; Mesylates; Nanostructures; Pest Control; Photolysis; Soil; Water Pollution, Chemical; Weed Control

Earthworms represent an important food source for many vertebrates and as a result, predators may encounter toxic effects via the food chain from consumption of contaminated worms. Therefore, including an assessment of xenobiotic to worms in risk assessment procedures is advisable. Here we studied the acute toxicity, bioaccumulation and elimination of ethofumesate enantiomers in earthworm, Eisenia fetida, in a soil. A slight difference in toxicity to earthworm between two enantiomers was found, and the calculated LC50 values for (+)-, rac- and (-)-ethofumesate were 4.51, 5.93 and 7.98 μg/cm(2), respectively, indicating that the acute toxicity of ethofumesate enantiomers was enantioselective. Earthworm can uptake ethofumesate but the bioaccumulation curve did not reach the steady state. In the elimination experiment, the concentrations of ethofumesate in earthworm declined following a first-order decay model with a short half life of 1.8d. The bioaccumulation and elimination of ethofumesate in earthworm were both nonenantioselective. In combination with other studies, a linear relationship between Log BSAFs and Log Kow was observed, and the Log BSAFs increased with increasing Log Kow. But the elimination rate did not show any correlation with the Kow value.

Topics: Animals; Benzofurans; Ecotoxicology; Laboratories; Mesylates; Oligochaeta; Soil; Soil Pollutants; Stereoisomerism; Structure-Activity Relationship

As a way to improve the efficacy to target organisms, new pesticide generation is based on technologically advanced coformulations of two or more active ingredients. One example is Betanal(®)Expert, a postemergence herbicide composed of an Advanced Micro Droplet coformulation of phenmedipham, desmedipham, and ethofumesate. Although its composed formulation brings an increase in the pesticide performance, it can also enhance its toxicity to nontarget species. Therefore, the present study intends to contribute with relevant information on ecotoxicological effects of Betanal(®)Expert and its active ingredients on a battery of bioassays using aquatic species from different trophic levels: bacteria (Vibrio fischeri), microalgae (Pseudokirchneriella subcapitata, Chlorella vulgaris, and Chlamydomonas pseudocostata), macrophyte (Lemna minor), and cladocerans (Daphnia magna and Daphnia longispina) species. Across the organisms tested and endpoints measured, different responses concerning the toxicity of the active ingredients were found: (i) phenmedipham was the most toxic to V. fischeri and L. minor; (ii) desmedipham was the most toxic to P. subcapitata, D. magna, and D. longispina; (iii) and ethofumesate was the most toxic to C. pseudocostata and C. vulgaris. Furthermore, for C. pseudocostata and daphnids, the toxicity observed for some active ingredients was higher than the toxicity of the commercial formulation. In fact, in an attempt to evaluate the contribution of each active ingredient to the overall toxicity of Betanal(®)Expert, it was observed that, in general, the toxicity values obtained for desmedipham and phenmedipham were close or even lower to the values determined for Betanal(®)Expert, indicating that the ethofumesate can act as an antagonist in the three-way coformulation. In spite of the most impaired species being the photosynthetic ones, this study also showed pernicious effects on nonphotosynthetic organisms with distinct target sites. Therefore, our results underline the importance of clarifying the mode of action and metabolic pathways of these compounds on nonphotosynthetic species.

Topics: Animals; Aquatic Organisms; Benzofurans; Biological Assay; Carbamates; Daphnia; Ecotoxicology; Herbicides; Mesylates; Toxicity Tests; Water Pollutants, Chemical

The potential use of nanoclays for modulating transfer properties of active agents in bio-sourced polymers was explored. For this purpose, new pesticide formulations were designed by combining wheat gluten, ethofumesate (model pesticide) and three montmorillonites (MMT) using a bi-vis extrusion process. Controlled release properties, evaluated through release experiments in water, were discussed in relation to the material formulations and their resulting structure. Partition coefficients were calculated from experimental data and diffusivity values were identified with a Fick's second law mechanistic model. The effect of temperature on release pattern was also evaluated and the activation energy of diffusion was determined. Ethofumesate release was slowed down for all wheat gluten based-formulations as compared to the commercial product. This slow release effect was increased in the presence of hydrophobic MMTs, due to a higher affinity for ethofumesate than for wheat gluten. Contrarily, hydrophilic MMT, displaying a greater affinity for wheat gluten than for ethofumesate seemed ineffective to slow down its release despite the tortuous pathway achieved through a well-exfoliated structure. To conclude, the release mechanisms would be rather governed by pesticide/MMT interactions than MMT/polymer matrix in the case of a hydrophobic pesticide such as ethofumesate and a hydrophilic matrix such as wheat gluten.

Topics: Bentonite; Benzofurans; Calorimetry, Differential Scanning; Glutens; Hydrophobic and Hydrophilic Interactions; Mesylates; Microscopy, Electron, Transmission; Nanostructures; Pesticides; Polymers

1. The stereoselective metabolism of ethofumesate (ETO) and its enantiomers in rabbit and rat liver microsomes have been studied by chiral high-performance liquid chromatography (HPLC) method. Two metabolites were detected in both liver microsomes in the presence of beta-nicotinamide adenine dinucleotide phosphate (NADPH). 2. The T(1/2) of (+)-ETO and (-)-ETO in rabbit liver microsomes were 12.2 and 4.7 min of rac-ETO and 25.9 and 6.7 of ETO enantiomers. However, the T(1/2) of (+)-ETO and (-)-ETO in rat liver microsomes were 5.3 and 5.9 min of rac-ETO and 7.8 and 10.6 of ETO enantiomers. The stereoselective selectivity is similar to the in vivo study. 3. After incubation of ETO enantiomers, stereoselectivity was present in the formation of ETO-OH enantiomer in rabbit liver microsomes, but stereoselectivity was not evident in rat liver microsomes. 4. There was no chiral inversion from the (+)-ETO to (-)-ETO or inversion from (-)-ETO to (+)-ETO in both rabbit and rat liver microsomes.

Topics: Animals; Benzofurans; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Kinetics; Male; Mesylates; Metabolic Networks and Pathways; Microsomes, Liver; NADP; Rabbits; Rats; Rats, Sprague-Dawley; Stereoisomerism

The stereoselective toxicokinetics of ethofumesate enantiomers following a single intravenous (i.v.) administration at doses of 30 mg/kg were investigated in rabbits. Plasma concentrations of (+)- and (-)-ethofumesate were analyzed by a validated chiral HPLC method that involved extraction of plasma with organic solvent followed by separation on a cellulose-Tris-(3,5-dimethylphenylcarbamate)-based chiral column and quantification by UV absorbance at 230 nm. Plasma concentration-time curves after i.v. administration were best described by an open two-compartment model. The concentration of the (-)-enantiomer decreased more rapidly than that of the (+)-enantiomer. Significant differences in toxicokinetic parameters between the two enantiomers indicated that stereoselective behavior occurred with the (-)-enantiomer being preferentially metabolized and eliminated.

Topics: Animals; Benzofurans; Chromatography, High Pressure Liquid; Herbicides; Male; Mesylates; Rabbits; Stereoisomerism; Tissue Distribution

The fate of five herbicides (glyphosate, glufosinate-ammonium, phenmedipham, ethofumesate and metamitron) was studied in two Finnish sugar beet fields for 26 months. Soil types were sandy loam and clay. Two different herbicide-tolerant sugar beet cultivars and three different herbicide application schedules were used. Meteorological data were collected throughout the study and soil properties were thoroughly analysed. An extensive data set of herbicide residue concentrations in soil was collected. Five different soil depths were sampled. The study was carried out using common Finnish agricultural practices and represents typical sugar beet cultivation conditions in Finland. The overall observed order of persistence was ethofumesate > glyphosate > phenmedipham > metamitron > glufosinate-ammonium. Only ethofumesate and glyphosate persisted until the subsequent spring. Seasonal variation in herbicide dissipation was very high and dissipation ceased almost completely during winter. During the 2 year experiment no indication of potential groundwater pollution risk was obtained, but herbicides may cause surface water pollution.

Topics: Aminobutyrates; Benzofurans; Biodegradation, Environmental; Carbamates; Chromatography, Gas; Chromatography, High Pressure Liquid; Finland; Glycine; Glyphosate; Herbicides; Kinetics; Mesylates; Pesticide Residues; Soil Pollutants; Triazines

Three sugar beet herbicides, ethofumesate, phenmedipham and metamitron, are currently used on conventional sugar beet cultivation, while new varieties of herbicide resistant (HR) sugar beet, tolerant of glyphosate or glufosinate-ammonium, are under field testing in Finland. Little knowledge has so far been available on the adsorption of these herbicides to Finnish soils. The adsorption of these five herbicides was studied using the batch equilibrium method in 21 soil samples collected from different depths. Soil properties like organic carbon content, texture, pH and partly the phosphorus and oxide content of the soils were tested against the adsorption coefficients of the herbicides. In general, the herbicides studied could be arranged according to their adsorption coefficients as follows: glyphosate>phenmedipham>ethofumesate approximately glufosinate-ammonium>metamitron, metamitron meaning the highest risk of leaching. None of the measured soil parameters could alone explain the adsorption mechanism of these five herbicides. The results can be used in model assessments of risk for leaching to ground water resulting from weed control of sugar beet in Finland.

Topics: Adsorption; Agriculture; Aminobutyrates; Benzofurans; Beta vulgaris; Carbamates; Finland; Herbicides; Hydrogen-Ion Concentration; Mesylates; Soil; Triazines; Water Pollution, Chemical

The effect of turfgrass cover on the leaching and dissipation of ethofumesate and halofenozide was studied. Sampling cylinders (20 cm diam. x 30 cm long) were placed vertically in plots of creeping bentgrass (Agrostis palustris Huds.), tall fescue (Festuca arundinaceae Schreb.), or bare soil. ethofumesate [(+/-)-2-ethoxy-2,3-dihydro-3,3-dimethylbenzofuran-5-yl methansulfonate] was applied at 840 g ai ha(-)(1) on September 21, 1997. Halofenozide (N-4-chlorobenzoyl-N'-benzoyl-N'-tert-butylhydrazine) was applied at 1680 g ai ha(-)(1) on August 30, 1998. Replicate sampling cylinders were removed 2 h after treatment and 4, 8, 16, 32, and 64 days after treatment. Sampling cylinders were sectioned by depths and soil extracts were assayed by HPLC with a pesticide detection limit of 0.01 mg kg(-)(1). Turfgrass was divided into verdure and thatch and analyzed separately. ethofumesate leaching in turfgrass was reduced by at least 95% compared to leaching in bare soil. The half-life of ethofumesate in bare soil was 51 days compared to 3 days in turfgrass. Halofenozide showed similar leaching with or without turfgrass. Fifty percent dissipation of halofenozide did not occur within 64 days, regardless of organic matter cover.

Topics: Benzoates; Benzofurans; Chromatography, High Pressure Liquid; Environmental Pollution; Half-Life; Herbicides; Hydrazines; Insecticides; Mesylates; Pesticide Residues; Poaceae; Soil; Soil Pollutants; Time Factors

Effects of vapours of two herbicides on plantlets of fourteen wild higher plant species and two bryophytes were screened in fumigation experiments using foliar injury, chlorophyll fluorescence and growth as response parameters. After vaporisation of the herbicides for 48 h, concentrations in the chambers reached 77 micrograms m-3 in the chlorpropham treatments and 184 ng m-3 in the ethofumesate treatments. Despite the higher concentrations of the volatile chlorpropham (vapour pressure, VP: 1.3 mP), plants showed no foliar injury, but vapours of this herbicide caused leaf crinkling in the agriophyte Agrostemma githago. The less volatile ethofumesate (VP: 0.56 mP) caused foliar injury in all higher species, with lowest no observed effect concentrations (NOECs) of 75 ng m-3. Chlorpropham affected growth only in Agrostemma, while ethofumesate reduced growth in one third of the higher plant species. Chlorophyll fluorescence proved to be a less suitable response parameter compared to foliar injury and growth. No adverse effects were observed in mosses, probably due to the slow growth and hence small doses of herbicides taken up. The extent of foliar injury due to ethofumesate showed a weak positive relationship to relative growth rates and specific leaf area in the tested higher plant species.

Topics: Benzofurans; Chlorpropham; Environmental Pollutants; Herbicides; Mesylates; No-Observed-Adverse-Effect Level; Plant Development; Plant Leaves; Volatilization

Triadimefon, a fungicide, and ethofumesate, an herbicide, are commonly applied to turfgrass in the Pacific Northwest, resulting in foliar residues. A simple and rapid method was developed to determine triadimefon and ethofumesate concentrations from dislodgeable foliar residues on turfgrass. Turfgrass samples were washed, and wash water containing surfactant (a 0.126% solution) was collected for residue analysis. This analytical method utilizes a 25 mm C(8) Empore disk and in-vial elution to quantitatively determine triadimefon and ethofumesate in 170 mL aqueous samples. The analytes were eluted by placing the disk in a 2 mL autosampler vial with 980 microL of ethyl acetate and 20 microL of 2-chlorolepidine, the internal standard, for analysis by GC/MS. The method quantitation limits are 0.29 microg/L for ethofumesate and 0.59 microg/L for triadimefon. The method detection limits are 0.047 microg/L and 0.29 microg/L for ethofumesate and triadimefon, respectively. Concentrations of triadimefon and ethofumesate from dislodgeable foliar residues from a field study are reported.

Topics: Benzofurans; Drug Residues; Filtration; Fungicides, Industrial; Herbicides; Mesylates; Molecular Structure; Poaceae; Triazoles