The Experts below are selected from a list of 222 Experts worldwide ranked by ideXlab platform
Etienne Benoit - One of the best experts on this subject based on the ideXlab platform.
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Mass spectrometry characterization of anticoagulant rodenticides and hydroxyl-metabolites.
Rapid Communications in Mass Spectrometry, 2020Co-Authors: Isabelle Fourel, Alexandra Berlioz-barbier, Etienne BenoitAbstract:RATIONALE Anticoagulant rodenticides (ARs) are used worldwide for rodent population control to protect human health and biodiversity, and to prevent agricultural and economical losses. Rodents may develop a metabolic resistance to ARs. In order to help understand the metabolic resistance, mass spectrometry was used to position the hydroxylated group of hydroxyl-metabolite of second-generation anticoagulant rodenticides (SGARs). METHODS Most ARs pesticides are derived from the 4-hydroxy coumarin/thiocoumarin family. We used low-resolution and high-resolution mass spectrometry to understand the fragmentation pathways of the ARs and their respective metabolites, and to better define the structure of their MS/MS product ions. RESULTS Seven specific product ions were evidenced for five ARs, with their respective chemical structures. Those ions were obtained from the mass spectra of the hydroxyl metabolites of four SGARs difenacoum (DFM), brodifacoum (BFM), Difethialone (DFTL) and flocoumafen (FLO) with different positions of the hydroxyl group. CONCLUSION The differences of chemical structure between DFM on the one hand and BFM, FLO and DFTL on the other could explain the differences of bioavailability between these two groups of molecules. The defined product ions will be used to investigate the part played by the metabolic issue in the field resistance of SGARs.
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enantiomeric fraction evaluation of the four stereoisomers of Difethialone in biological matrices of rat by two enantioselective liquid chromatography tandem mass spectrometry methods chiral stationary phase or derivatization
Journal of Chromatography A, 2020Co-Authors: Isabelle Fourel, Etienne Benoit, Virginie LattardAbstract:Abstract The need for the control of rodent populations with anticoagulant rodenticides remains actual, and enantioselective analytical methods are mandatory to understand ecotoxicity issues of those chiral pesticides. This study presents two enantioselective methods to achieve the residue levels and differentiated persistence of the four stereoisomers of Difethialone (called in this work E1-trans, E2-cis, E3-cis and E4-trans), which is one of the most toxic second generation anticoagulant rodenticide. Their enantiomeric fraction evaluation in biological matrices of rats was determined by two LC-MS/MS methods. The first one (chiral-LC-MS/MS) combined a chiral column employed in reversed-phase mode (with acetonitrile-water mobile phase) to be compatible with mass spectrometry detection. The second one was also a LC-MS/MS method but with a reversed phase column after a derivatization step with (1S)-(−)-camphanic chloride. Extraction process combined Solid-Liquid extraction and sorbent cartridges. The methods were fully validated. The chiral column was chosen as a reference method for our laboratory because it was quicker and cheaper, and enantioresolution and sensitivity were better. This chiral-LC-MS/MS method was used to measure the enantiomeric fraction of the four stereoisomers of Difethialone in rodent biological matrices (liver, plasma, blood and feces) of female rats treated with 3.5 mg/kg of Difethialone. The results showed that metabolism is not the same for all the stereoisomers: cis-E3-Difethialone was the most persistent, and E4-trans-Difethialone was the most quickly eliminated. This chiral-LC-MS/MS method will be used to study the pharmacokinetics of the four stereoisomers of Difethialone, and for ecotoxicological surveillance to evaluate the specific persistence of each stereoisomer of Difethialone in case of secondary exposure of wildlife non-target species.
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Comparative biological properties of the four stereoisomers of Difethialone, a second-generation anticoagulant rodenticide, in rats: development of a model allowing to choose the appropriate stereoisomeric ratio
Archives of Toxicology, 2020Co-Authors: Sébastien Lefebvre, Isabelle Fourel, Etienne Benoit, Nolan Chatron, Hervé Caruel, Virginie LattardAbstract:The current management of rodent pest populations is based on second-generation anticoagulant rodenticides (SGAR). These molecules, of which Difethialone is part, are much more efficient than the first generation. Nevertheless, this efficiency comes with a major drawback, SGARs are tissue persistent that increases the exposure of rodent predators to them. According to its chemical structure, Difethialone has four stereoisomers, whose specific inhibition potency and pharmacokinetic have never been described and might be useful to design new eco-friendly rodenticides. The study aimed to investigate the ability to inhibit anticoagulant target enzyme (VKORC1) and the pharmacokinetics in rats of the four Difethialone stereoisomers in rats. We show that stereoisomers are all highly efficient to inhibit VKORC1 activity, but they have distinct initial half-life with 6.0 h, 25.4 h, 69.3 h, and 82.3 h for, respectively, E4- trans , E2- cis , E1- trans , and E3- cis stereoisomer. These results open the way of the development of eco-friendly and efficient rodenticide by mixing some of these stereoisomers. Preferential incorporation of the E4- trans stereoisomer (high inhibitory VKORC1 potency, relatively shorter liver half-life) into Difethialone rodenticides baits might result in a more eco-friendly product than current commercially available Difethialone formulations. In addition, we put forward modelling to help design bait according to the circumstance of use (presence of non-target species, food competition, etc.) by modulating the theorical AUC and and the theorical concentration of the product at the death of the rodent pest. Thus, this modeling might allow to diminish the use of laboratory animal in assay. Difethialone stereoisomers are potent inhibitors of VKORC1 enzyme activity. Difethialone stereoisomer initial half-lives range from 6 to 69.3 h. E1-trans and E3-cis initial half-lives are similar and greater than other stereoisomers. Modeling can be used to refine the bait formulation process and to diminish the use of laboratory animals.
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Monitoring of antivitamin K-dependent anticoagulation in rodents - Towards an evolution of the methodology to detect resistance in rodents.
Pesticide Biochemistry and Physiology, 2017Co-Authors: Sébastien Lefebvre, Etienne Benoit, Benoit Rannou, Claire Hascoët, Marlène Damin-pernik, Virginie LattardAbstract:Abstract Vitamin K antagonists are used as rodenticides for pest control management. In rodents, prothrombin time is used to monitor their effect despite its limits and the emergence of many coagulation methods. The aim of this study is to explore different coagulation monitoring methods in order to propose the best method and the best parameter to monitor vitamin K antagonists effect in rodents. The coagulation function was thus monitored with global coagulation assays and specialty assays after Difethialone administration in rats. Despite many parameters obtained by thromboelastometry, only clotting time and clot formation time obtained by ExTEM were modified. Their evolution was fast with doubling time respectively of 4.0 h and 3.7 h but their increases were delayed with a lag time higher than 8 h. Conversely, prothrombin time evolution presented a lag time of only 2 h, but a higher doubling time of 7.2 h. The measurements of factor VII and X activities were the most sensitive assays to monitor vitamin K antagonists effect with almost no lag time and the fastest evolution. Nevertheless, factor X was shown to be the only key factor driving prothrombin time. Monitoring factor X activity enables to follow most effectively the anticoagulation status in rats after rodenticides administration.
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Core-shell LC-MS/MS method for quantification of second generation anticoagulant rodenticides diastereoisomers in rat liver in relationship with exposure of wild rats.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2016Co-Authors: Isabelle Fourel, Etienne Benoit, Marlène Damin-pernik, Virginie LattardAbstract:Second generation anticoagulant rodenticides (SGARs), pesticides used worldwide to control rodent populations, exist in two diastereoisomer chemical species because they own two stereogenic centers. A core-shell LC-MS/MS multi-residue method for comprehensive quantitative analysis of the diastereoisomers of five SGARs as well as three first generation anticoagulant rodenticide molecules has been fully validated in liver of rats according to a bioanalytical guideline. A core-shell column (superficially porous particles) has been chosen for its ability to separate the diastereomers of bromadiolone, difenacoum, brodifacoum, flocoumafen and Difethialone and for its robustness to rat liver extracts. The highly selective chromatographic separation of the diastereoisomers contributes to good signal to noise ratios and then enhances the sensitivity of the method compared to the ones of fully porous columns. An elution gradient has been optimized with 10mM ammonium acetate and acetonitrile as aqueous/organic mobile phase respectively. Triple quadrupole mass detector has been used to achieve specifity and LLOQ from 0.92 to 2.2ng/g for each diastereoisomer, or first generation anticoagulant rodenticides. Then we evidenced diastereoisomeric ratios in liver of rats issued from not controlled exposure of wild rats (Rattus norvegicus) trapped in a French Parisian park through a campaign of rodent eradication. We compared them to diastereoisomeric ratios in SGARs commercial baits that contain both isomers, and showed that one of the two diastereoiomers had nearly disappeared in liver of rats. The proportions of cis-bromadiolone and trans-difenacoum were really lowered compared to the baits: 5/7 and 9/12 rats had only trans-bromadiolone and cis-difenacoum hepatic residues respectively. Liver persistence of the two diastereoisomers of bromadiolone and difenacoum was different due to differences in their pharmacokinetics in wild rats. The new core-shell LC-MS/MS method is particularly well adapted for further exploration of diastereoisomers ratios in rodent and predatory wildlife biological samples in order to evaluate ecological consequences of actual baits, to explore new formulated baits with a good balance between efficacity (ability to kill rodents) and diastereoisomers persistence, and hopefully to mitigate exposure of non-target species.
Virginie Lattard - One of the best experts on this subject based on the ideXlab platform.
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enantiomeric fraction evaluation of the four stereoisomers of Difethialone in biological matrices of rat by two enantioselective liquid chromatography tandem mass spectrometry methods chiral stationary phase or derivatization
Journal of Chromatography A, 2020Co-Authors: Isabelle Fourel, Etienne Benoit, Virginie LattardAbstract:Abstract The need for the control of rodent populations with anticoagulant rodenticides remains actual, and enantioselective analytical methods are mandatory to understand ecotoxicity issues of those chiral pesticides. This study presents two enantioselective methods to achieve the residue levels and differentiated persistence of the four stereoisomers of Difethialone (called in this work E1-trans, E2-cis, E3-cis and E4-trans), which is one of the most toxic second generation anticoagulant rodenticide. Their enantiomeric fraction evaluation in biological matrices of rats was determined by two LC-MS/MS methods. The first one (chiral-LC-MS/MS) combined a chiral column employed in reversed-phase mode (with acetonitrile-water mobile phase) to be compatible with mass spectrometry detection. The second one was also a LC-MS/MS method but with a reversed phase column after a derivatization step with (1S)-(−)-camphanic chloride. Extraction process combined Solid-Liquid extraction and sorbent cartridges. The methods were fully validated. The chiral column was chosen as a reference method for our laboratory because it was quicker and cheaper, and enantioresolution and sensitivity were better. This chiral-LC-MS/MS method was used to measure the enantiomeric fraction of the four stereoisomers of Difethialone in rodent biological matrices (liver, plasma, blood and feces) of female rats treated with 3.5 mg/kg of Difethialone. The results showed that metabolism is not the same for all the stereoisomers: cis-E3-Difethialone was the most persistent, and E4-trans-Difethialone was the most quickly eliminated. This chiral-LC-MS/MS method will be used to study the pharmacokinetics of the four stereoisomers of Difethialone, and for ecotoxicological surveillance to evaluate the specific persistence of each stereoisomer of Difethialone in case of secondary exposure of wildlife non-target species.
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Comparative biological properties of the four stereoisomers of Difethialone, a second-generation anticoagulant rodenticide, in rats: development of a model allowing to choose the appropriate stereoisomeric ratio
Archives of Toxicology, 2020Co-Authors: Sébastien Lefebvre, Isabelle Fourel, Etienne Benoit, Nolan Chatron, Hervé Caruel, Virginie LattardAbstract:The current management of rodent pest populations is based on second-generation anticoagulant rodenticides (SGAR). These molecules, of which Difethialone is part, are much more efficient than the first generation. Nevertheless, this efficiency comes with a major drawback, SGARs are tissue persistent that increases the exposure of rodent predators to them. According to its chemical structure, Difethialone has four stereoisomers, whose specific inhibition potency and pharmacokinetic have never been described and might be useful to design new eco-friendly rodenticides. The study aimed to investigate the ability to inhibit anticoagulant target enzyme (VKORC1) and the pharmacokinetics in rats of the four Difethialone stereoisomers in rats. We show that stereoisomers are all highly efficient to inhibit VKORC1 activity, but they have distinct initial half-life with 6.0 h, 25.4 h, 69.3 h, and 82.3 h for, respectively, E4- trans , E2- cis , E1- trans , and E3- cis stereoisomer. These results open the way of the development of eco-friendly and efficient rodenticide by mixing some of these stereoisomers. Preferential incorporation of the E4- trans stereoisomer (high inhibitory VKORC1 potency, relatively shorter liver half-life) into Difethialone rodenticides baits might result in a more eco-friendly product than current commercially available Difethialone formulations. In addition, we put forward modelling to help design bait according to the circumstance of use (presence of non-target species, food competition, etc.) by modulating the theorical AUC and and the theorical concentration of the product at the death of the rodent pest. Thus, this modeling might allow to diminish the use of laboratory animal in assay. Difethialone stereoisomers are potent inhibitors of VKORC1 enzyme activity. Difethialone stereoisomer initial half-lives range from 6 to 69.3 h. E1-trans and E3-cis initial half-lives are similar and greater than other stereoisomers. Modeling can be used to refine the bait formulation process and to diminish the use of laboratory animals.
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Thrombin generation test: A reliable tool to evaluate the pharmacodynamics of vitamin K antagonist rodenticides in rats.
Pesticide Biochemistry and Physiology, 2018Co-Authors: G Jourdi, Sébastien Lefebvre, Virginie Lattard, Bernard Le Bonniec, Emmanuel Curis, Pascale Gaussem, Virginie SiguretAbstract:Vitamin K antagonist rodenticide pharmacodynamics (PD) is studied in rodents with traditional laboratory tests. We wondered if thrombin generation test (TGT) could add value. Difethialone (10mg/kg) was administered per os to 97 OFA-Sprague Dawley rats. PD was studied over a 72h-period using the Calibrated Automated Thrombogram on platelet poor plasma before and after intoxication (3 female and 3 male rats for each 13 time points) and TGT parameters were compared with the prothrombin time (PT) and vitamin K dependent factor activities previously reported. Following intoxication, preliminary tests evidenced rapid and full inhibition of thrombin generation triggered with 5 or 20pM human recombinant tissue factor. To study the evolution of TGT parameters following Difethialone intake, we adapted the test by complementing intoxicated rat samples with pooled normal rat plasma (3/1, v/v). Adapted TGT confirmed the known higher procoagulant basal level in females compared to males through higher endogenous thrombin potential (ETP) and peak height (PH) (p
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Monitoring of antivitamin K-dependent anticoagulation in rodents - Towards an evolution of the methodology to detect resistance in rodents.
Pesticide Biochemistry and Physiology, 2017Co-Authors: Sébastien Lefebvre, Etienne Benoit, Benoit Rannou, Claire Hascoët, Marlène Damin-pernik, Virginie LattardAbstract:Abstract Vitamin K antagonists are used as rodenticides for pest control management. In rodents, prothrombin time is used to monitor their effect despite its limits and the emergence of many coagulation methods. The aim of this study is to explore different coagulation monitoring methods in order to propose the best method and the best parameter to monitor vitamin K antagonists effect in rodents. The coagulation function was thus monitored with global coagulation assays and specialty assays after Difethialone administration in rats. Despite many parameters obtained by thromboelastometry, only clotting time and clot formation time obtained by ExTEM were modified. Their evolution was fast with doubling time respectively of 4.0 h and 3.7 h but their increases were delayed with a lag time higher than 8 h. Conversely, prothrombin time evolution presented a lag time of only 2 h, but a higher doubling time of 7.2 h. The measurements of factor VII and X activities were the most sensitive assays to monitor vitamin K antagonists effect with almost no lag time and the fastest evolution. Nevertheless, factor X was shown to be the only key factor driving prothrombin time. Monitoring factor X activity enables to follow most effectively the anticoagulation status in rats after rodenticides administration.
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Core-shell LC-MS/MS method for quantification of second generation anticoagulant rodenticides diastereoisomers in rat liver in relationship with exposure of wild rats.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2016Co-Authors: Isabelle Fourel, Etienne Benoit, Marlène Damin-pernik, Virginie LattardAbstract:Second generation anticoagulant rodenticides (SGARs), pesticides used worldwide to control rodent populations, exist in two diastereoisomer chemical species because they own two stereogenic centers. A core-shell LC-MS/MS multi-residue method for comprehensive quantitative analysis of the diastereoisomers of five SGARs as well as three first generation anticoagulant rodenticide molecules has been fully validated in liver of rats according to a bioanalytical guideline. A core-shell column (superficially porous particles) has been chosen for its ability to separate the diastereomers of bromadiolone, difenacoum, brodifacoum, flocoumafen and Difethialone and for its robustness to rat liver extracts. The highly selective chromatographic separation of the diastereoisomers contributes to good signal to noise ratios and then enhances the sensitivity of the method compared to the ones of fully porous columns. An elution gradient has been optimized with 10mM ammonium acetate and acetonitrile as aqueous/organic mobile phase respectively. Triple quadrupole mass detector has been used to achieve specifity and LLOQ from 0.92 to 2.2ng/g for each diastereoisomer, or first generation anticoagulant rodenticides. Then we evidenced diastereoisomeric ratios in liver of rats issued from not controlled exposure of wild rats (Rattus norvegicus) trapped in a French Parisian park through a campaign of rodent eradication. We compared them to diastereoisomeric ratios in SGARs commercial baits that contain both isomers, and showed that one of the two diastereoiomers had nearly disappeared in liver of rats. The proportions of cis-bromadiolone and trans-difenacoum were really lowered compared to the baits: 5/7 and 9/12 rats had only trans-bromadiolone and cis-difenacoum hepatic residues respectively. Liver persistence of the two diastereoisomers of bromadiolone and difenacoum was different due to differences in their pharmacokinetics in wild rats. The new core-shell LC-MS/MS method is particularly well adapted for further exploration of diastereoisomers ratios in rodent and predatory wildlife biological samples in order to evaluate ecological consequences of actual baits, to explore new formulated baits with a good balance between efficacity (ability to kill rodents) and diastereoisomers persistence, and hopefully to mitigate exposure of non-target species.
Isabelle Fourel - One of the best experts on this subject based on the ideXlab platform.
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Non-invasive monitoring of red fox exposure to rodenticides from scats
Ecological Indicators, 2020Co-Authors: Yves Prat-mairet, Isabelle Fourel, Jacques Barrat, Mickaël Sage, Patrick Giraudoux, Michael CoeurdassierAbstract:Abstract Exposure of wildlife to anticoagulant rodenticides is mainly assessed by analysing residues in the tissues, notably liver, of dead animals. Recent finding suggested that the analysis of active ingredients in mammal scats sampled in the field could be used as a non-invasive method to monitor non-lethal exposure in populations. Here, we measure experimentally the persistence of 6 anticoagulant rodenticides in fox scats when placed under natural conditions. Six foxes were fed with voles dosed with brodifacoum, bromadiolone, chlorophacinone, warfarin, difenacoum and Difethialone in controlled conditions and their faeces were collected. Then, the scats were placed outside, thus exposed to weathering, and sampled up to four months later to measure the concentrations of the 6 rodenticides. We showed that both the concentrations and the occurrence of residues in the scats decreased rapidly for all these pesticides. Based on concentrations, the degradation half-lives ranged from 5.26 days for chlorophacinone to 7.98 days for bromadiolone. Furthermore, the probability of sampling a scat containing detectable residues decreased by 10% after 7d, 2d, 10d, 5d, 3d and 10d for warfarin, chlorophacinone, bromadiolone, brodifacoum, difenacoum and Difethialone respectively. Thus, in terms of using residues in scats to monitor fox exposure to rodenticides, we recommend first, to clear the studied areas of old faeces and then, sample scats after a short period, ideally
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Mass spectrometry characterization of anticoagulant rodenticides and hydroxyl-metabolites.
Rapid Communications in Mass Spectrometry, 2020Co-Authors: Isabelle Fourel, Alexandra Berlioz-barbier, Etienne BenoitAbstract:RATIONALE Anticoagulant rodenticides (ARs) are used worldwide for rodent population control to protect human health and biodiversity, and to prevent agricultural and economical losses. Rodents may develop a metabolic resistance to ARs. In order to help understand the metabolic resistance, mass spectrometry was used to position the hydroxylated group of hydroxyl-metabolite of second-generation anticoagulant rodenticides (SGARs). METHODS Most ARs pesticides are derived from the 4-hydroxy coumarin/thiocoumarin family. We used low-resolution and high-resolution mass spectrometry to understand the fragmentation pathways of the ARs and their respective metabolites, and to better define the structure of their MS/MS product ions. RESULTS Seven specific product ions were evidenced for five ARs, with their respective chemical structures. Those ions were obtained from the mass spectra of the hydroxyl metabolites of four SGARs difenacoum (DFM), brodifacoum (BFM), Difethialone (DFTL) and flocoumafen (FLO) with different positions of the hydroxyl group. CONCLUSION The differences of chemical structure between DFM on the one hand and BFM, FLO and DFTL on the other could explain the differences of bioavailability between these two groups of molecules. The defined product ions will be used to investigate the part played by the metabolic issue in the field resistance of SGARs.
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enantiomeric fraction evaluation of the four stereoisomers of Difethialone in biological matrices of rat by two enantioselective liquid chromatography tandem mass spectrometry methods chiral stationary phase or derivatization
Journal of Chromatography A, 2020Co-Authors: Isabelle Fourel, Etienne Benoit, Virginie LattardAbstract:Abstract The need for the control of rodent populations with anticoagulant rodenticides remains actual, and enantioselective analytical methods are mandatory to understand ecotoxicity issues of those chiral pesticides. This study presents two enantioselective methods to achieve the residue levels and differentiated persistence of the four stereoisomers of Difethialone (called in this work E1-trans, E2-cis, E3-cis and E4-trans), which is one of the most toxic second generation anticoagulant rodenticide. Their enantiomeric fraction evaluation in biological matrices of rats was determined by two LC-MS/MS methods. The first one (chiral-LC-MS/MS) combined a chiral column employed in reversed-phase mode (with acetonitrile-water mobile phase) to be compatible with mass spectrometry detection. The second one was also a LC-MS/MS method but with a reversed phase column after a derivatization step with (1S)-(−)-camphanic chloride. Extraction process combined Solid-Liquid extraction and sorbent cartridges. The methods were fully validated. The chiral column was chosen as a reference method for our laboratory because it was quicker and cheaper, and enantioresolution and sensitivity were better. This chiral-LC-MS/MS method was used to measure the enantiomeric fraction of the four stereoisomers of Difethialone in rodent biological matrices (liver, plasma, blood and feces) of female rats treated with 3.5 mg/kg of Difethialone. The results showed that metabolism is not the same for all the stereoisomers: cis-E3-Difethialone was the most persistent, and E4-trans-Difethialone was the most quickly eliminated. This chiral-LC-MS/MS method will be used to study the pharmacokinetics of the four stereoisomers of Difethialone, and for ecotoxicological surveillance to evaluate the specific persistence of each stereoisomer of Difethialone in case of secondary exposure of wildlife non-target species.
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Comparative biological properties of the four stereoisomers of Difethialone, a second-generation anticoagulant rodenticide, in rats: development of a model allowing to choose the appropriate stereoisomeric ratio
Archives of Toxicology, 2020Co-Authors: Sébastien Lefebvre, Isabelle Fourel, Etienne Benoit, Nolan Chatron, Hervé Caruel, Virginie LattardAbstract:The current management of rodent pest populations is based on second-generation anticoagulant rodenticides (SGAR). These molecules, of which Difethialone is part, are much more efficient than the first generation. Nevertheless, this efficiency comes with a major drawback, SGARs are tissue persistent that increases the exposure of rodent predators to them. According to its chemical structure, Difethialone has four stereoisomers, whose specific inhibition potency and pharmacokinetic have never been described and might be useful to design new eco-friendly rodenticides. The study aimed to investigate the ability to inhibit anticoagulant target enzyme (VKORC1) and the pharmacokinetics in rats of the four Difethialone stereoisomers in rats. We show that stereoisomers are all highly efficient to inhibit VKORC1 activity, but they have distinct initial half-life with 6.0 h, 25.4 h, 69.3 h, and 82.3 h for, respectively, E4- trans , E2- cis , E1- trans , and E3- cis stereoisomer. These results open the way of the development of eco-friendly and efficient rodenticide by mixing some of these stereoisomers. Preferential incorporation of the E4- trans stereoisomer (high inhibitory VKORC1 potency, relatively shorter liver half-life) into Difethialone rodenticides baits might result in a more eco-friendly product than current commercially available Difethialone formulations. In addition, we put forward modelling to help design bait according to the circumstance of use (presence of non-target species, food competition, etc.) by modulating the theorical AUC and and the theorical concentration of the product at the death of the rodent pest. Thus, this modeling might allow to diminish the use of laboratory animal in assay. Difethialone stereoisomers are potent inhibitors of VKORC1 enzyme activity. Difethialone stereoisomer initial half-lives range from 6 to 69.3 h. E1-trans and E3-cis initial half-lives are similar and greater than other stereoisomers. Modeling can be used to refine the bait formulation process and to diminish the use of laboratory animals.
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Core-shell LC-MS/MS method for quantification of second generation anticoagulant rodenticides diastereoisomers in rat liver in relationship with exposure of wild rats.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2016Co-Authors: Isabelle Fourel, Etienne Benoit, Marlène Damin-pernik, Virginie LattardAbstract:Second generation anticoagulant rodenticides (SGARs), pesticides used worldwide to control rodent populations, exist in two diastereoisomer chemical species because they own two stereogenic centers. A core-shell LC-MS/MS multi-residue method for comprehensive quantitative analysis of the diastereoisomers of five SGARs as well as three first generation anticoagulant rodenticide molecules has been fully validated in liver of rats according to a bioanalytical guideline. A core-shell column (superficially porous particles) has been chosen for its ability to separate the diastereomers of bromadiolone, difenacoum, brodifacoum, flocoumafen and Difethialone and for its robustness to rat liver extracts. The highly selective chromatographic separation of the diastereoisomers contributes to good signal to noise ratios and then enhances the sensitivity of the method compared to the ones of fully porous columns. An elution gradient has been optimized with 10mM ammonium acetate and acetonitrile as aqueous/organic mobile phase respectively. Triple quadrupole mass detector has been used to achieve specifity and LLOQ from 0.92 to 2.2ng/g for each diastereoisomer, or first generation anticoagulant rodenticides. Then we evidenced diastereoisomeric ratios in liver of rats issued from not controlled exposure of wild rats (Rattus norvegicus) trapped in a French Parisian park through a campaign of rodent eradication. We compared them to diastereoisomeric ratios in SGARs commercial baits that contain both isomers, and showed that one of the two diastereoiomers had nearly disappeared in liver of rats. The proportions of cis-bromadiolone and trans-difenacoum were really lowered compared to the baits: 5/7 and 9/12 rats had only trans-bromadiolone and cis-difenacoum hepatic residues respectively. Liver persistence of the two diastereoisomers of bromadiolone and difenacoum was different due to differences in their pharmacokinetics in wild rats. The new core-shell LC-MS/MS method is particularly well adapted for further exploration of diastereoisomers ratios in rodent and predatory wildlife biological samples in order to evaluate ecological consequences of actual baits, to explore new formulated baits with a good balance between efficacity (ability to kill rodents) and diastereoisomers persistence, and hopefully to mitigate exposure of non-target species.
Maureen Murray - One of the best experts on this subject based on the ideXlab platform.
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Anticoagulant rodenticide exposure and toxicosis in four species of birds of prey in Massachusetts, USA, 2012–2016, in relation to use of rodenticides by pest management professionals
Ecotoxicology, 2017Co-Authors: Maureen MurrayAbstract:Restrictions on second-generation anticoagulant rodenticides (SGARs) in the United States, which were partially implemented in 2011, prohibit the sale of SGAR products through general consumer outlets to minimize use by non-professional or non-agricultural applicators. This study analyzed liver tissue from four species of birds of prey admitted to a wildlife clinic in Massachusetts, USA, from 2012–2016 for residues of anticoagulant rodenticides (ARs). Ninety-four birds were analyzed; 16 were symptomatic for AR toxicosis, and 78 asymptomatic. Ninety-six percent of all birds tested were positive for SGARs: 100% of those diagnosed with AR toxicosis ante-mortem and/or post-mortem and 95% of subclinically exposed birds. Brodifacoum was found in 95% of all birds. Sixty-six percent of all birds contained residues of two or more SGARs. A significant increase in exposures to multiple SGARs occurred in later years in the study. Pesticide use reports (PURs) filed with the Massachusetts Department of Agricultural Resources were reviewed to determine the frequency of use of different ARs by pest management professionals (PMPs) across five years. This study finds that the three SGARs favored by PMPs—bromadiolone, Difethialone, brodifacoum—were present in combination in the majority of birds, with increases in multiple exposures driven by increased detections of bromadiolone and Difethialone. Continued monitoring of AR residues in nontarget species following full implementation of sales and packaging restrictions in the US is needed in order to elucidate the role of PMP use of SGARs in wildlife exposures and to evaluate the effectiveness of current mitigation measures.
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Anticoagulant rodenticide exposure and toxicosis in four species of birds of prey in Massachusetts, USA, 2012-2016, in relation to use of rodenticides by pest management professionals.
Ecotoxicology, 2017Co-Authors: Maureen MurrayAbstract:Restrictions on second-generation anticoagulant rodenticides (SGARs) in the United States, which were partially implemented in 2011, prohibit the sale of SGAR products through general consumer outlets to minimize use by non-professional or non-agricultural applicators. This study analyzed liver tissue from four species of birds of prey admitted to a wildlife clinic in Massachusetts, USA, from 2012–2016 for residues of anticoagulant rodenticides (ARs). Ninety-four birds were analyzed; 16 were symptomatic for AR toxicosis, and 78 asymptomatic. Ninety-six percent of all birds tested were positive for SGARs: 100% of those diagnosed with AR toxicosis ante-mortem and/or post-mortem and 95% of subclinically exposed birds. Brodifacoum was found in 95% of all birds. Sixty-six percent of all birds contained residues of two or more SGARs. A significant increase in exposures to multiple SGARs occurred in later years in the study. Pesticide use reports (PURs) filed with the Massachusetts Department of Agricultural Resources were reviewed to determine the frequency of use of different ARs by pest management professionals (PMPs) across five years. This study finds that the three SGARs favored by PMPs—bromadiolone, Difethialone, brodifacoum—were present in combination in the majority of birds, with increases in multiple exposures driven by increased detections of bromadiolone and Difethialone. Continued monitoring of AR residues in nontarget species following full implementation of sales and packaging restrictions in the US is needed in order to elucidate the role of PMP use of SGARs in wildlife exposures and to evaluate the effectiveness of current mitigation measures.
V. R. Parshad - One of the best experts on this subject based on the ideXlab platform.
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Laboratory and field evaluation of three chemical compounds for improving the acceptance of 0.0025% Difethialone (an anti-coagulant rodenticide) baitby rodents
International pest control, 2020Co-Authors: Harjit Kaur, V. R. ParshadAbstract:The efficacy of three chemical compounds viz. 1.5% dimethyl sulphoxide (DMSO), 1% phenyl acetic acid (PAA) and 1% carbon disulphide (CS 2 ) was tested for improving the acceptance of 0.0025% Difethialone bait by Bandicota bengalensis in bi-choice feeding tests using wheat (WSO) and rice (RSO) semolina as cereal, sugar and groundnut oil in 93:5:2 ratio. Wheat and rice fields were infested with rodents - B. bengalensis > Mus musculus > Tatera indica. The DMSO and the CS 2 improved the per cent acceptance of both (WSO and RSO) poison baits in the laboratory by B. bengalensis. However, 1% CS 2 was effective in improving the per cent acceptance significantly (p>0.05) when WSO poison bait was offered in the rice crop and RSO poison bait in the wheat crop ( i.e. different bait to the crop) but non-significantly (p 0.05) with 1% PAA both in the laboratory and in field tests. While this chemical was preferred non-significantly in WSO poison bait in the laboratory it was rejected in both crops by rodents. These differences in effectiveness of compounds might be due to changed palatability of the poison bait by the bait base and the competing food resources. These results revealed that although these chemical compounds improved the acceptance of poison bait by rodents, the bait constituents and the environment i.e. laboratory, rice crop or wheat crop field are crucial factors affecting performance of any rodenticide.
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laboratory and field evaluation of three chemical compounds for improving the acceptance of 0 0025 Difethialone an anti coagulant rodenticide baitby rodents
International pest control, 2004Co-Authors: Harjit Kaur, V. R. ParshadAbstract:The efficacy of three chemical compounds viz. 1.5% dimethyl sulphoxide (DMSO), 1% phenyl acetic acid (PAA) and 1% carbon disulphide (CS 2 ) was tested for improving the acceptance of 0.0025% Difethialone bait by Bandicota bengalensis in bi-choice feeding tests using wheat (WSO) and rice (RSO) semolina as cereal, sugar and groundnut oil in 93:5:2 ratio. Wheat and rice fields were infested with rodents - B. bengalensis > Mus musculus > Tatera indica. The DMSO and the CS 2 improved the per cent acceptance of both (WSO and RSO) poison baits in the laboratory by B. bengalensis. However, 1% CS 2 was effective in improving the per cent acceptance significantly (p>0.05) when WSO poison bait was offered in the rice crop and RSO poison bait in the wheat crop ( i.e. different bait to the crop) but non-significantly (p 0.05) with 1% PAA both in the laboratory and in field tests. While this chemical was preferred non-significantly in WSO poison bait in the laboratory it was rejected in both crops by rodents. These differences in effectiveness of compounds might be due to changed palatability of the poison bait by the bait base and the competing food resources. These results revealed that although these chemical compounds improved the acceptance of poison bait by rodents, the bait constituents and the environment i.e. laboratory, rice crop or wheat crop field are crucial factors affecting performance of any rodenticide.
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Carbon disulphide for improving the efficacy of rodenticide baiting and trapping of the house rat, Rattus rattus L.
International Biodeterioration & Biodegradation, 2002Co-Authors: V. R. ParshadAbstract:Abstract Rodenticide baiting and trapping are the common methods for the control of the house rat, Rattus rattus, which is a predominant commensal and agricultural pest throughout the tropic and sub-tropic regions of the world. During the present studies, a synthetic form of carbon disulphide (CS2), which is considered to be an artificial semiochemical involved in mediating socially induced food choices, at its 0.5%, 1% and 2% concentrations in cereal bait (mixture of broken wheat grains, sugar powder and groundnut oil 96 : 2 : 2), attracted both male and female R. rattus in bio-choice feeding tests with individual rats and pen experiments with groups of 10 rats and also in field experiments in poultry house premises. Addition of 1% CS2 in 2% zinc phosphide, 0.005% bromadiolone and 0.0025% Difethialone baits significantly improved bait acceptance by R. rattus. (Corresponding values of per cent acceptance of scented bait over the unscented bait were 77.3, 74.2 and 65.9.) Similarly a greater number of rats were trapped with cereal bait containing 1% CS2 than without it in pen and field experiments. In poultry houses CS2-scented bait was effective in improving the trappability of rats during the first 3 days, after which it did not have a significant effect on the residual population.
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agro ecological variations in food preference behaviour of bandicota bengalensis in rice wheat cropping system
Journal of research, 2002Co-Authors: H. Kaur, V. R. ParshadAbstract:Field evaluation of semolina baits of rice (RSO) and wheat (WSO), i.e., semolina like particles of size 0.000216–0.001 cu mm of rice (PR 106) or wheat (HD 2329), mixed with sugar and groundnut oil in ratio 93:5:2 and rodenticide baits (0.005% bromadiolone, 0.0375% coumatetralyl and 0.0025% Difethialone) at different stages of wheat and rice crops revealed that bait preference of rodents was affected by the area. The rodents preferred to eat WSO plain bait and rodenticide baits prepared in this bait over their RSO alternative baits in rice and wheat fields at Mukatsar while they preferred RSO plain bait and rodenticide baits prepared in semolina bait of rice over their WSO alternative baits in rice and wheat fields at Ludhiana. Bandicota bangalensis was predominant rodent pest in both the locations. Thus, for effective control of B. bengalensis in different agro-ecological regions, different bait formulations are needed.