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Min Shen - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of Brodifacoum-induced Toxicity by Metabonomics Approach Based on HPLC-TOF-MS
Fa yi xue za zhi, 2017Co-Authors: Hui Yan, Xian-yi Zhuo, Bao-hua Shen, Ping Xiang, Min ShenAbstract:OBJECTIVES To analyse the metabolic changes in urine of rats with Brodifacoum intoxication, and to reveal the molecular mechanism of Brodifacoum-induced toxicity on rats. METHODS By establishing a Brodifacoum poisoning rats model, the urine metabolic profiling data of rats were acquired using high performance liquid chromatography-time of flight mass spectrometry （HPLC-TOF-MS）. The orthogonal partial least squares analysis-discrimination analysis （OPLS-DA） was applied for the multivariate statistics and the discovery of differential metabolites closely related to toxicity of Brodifacoum. RESULTS OPLS-DA score plot showed that the urinary metabolic at different time points before and after drug administration had good similarity within time period and presented clustering phenomenon. Comparing the urine samples of rats before drug administration with which after drug administration, twenty-two metabolites related to Brodifacoum-induced toxicity were selected. CONCLUSIONS The toxic effect of Brodifacoum worked by disturbing the metabolic pathways in rats such as tricarboxylic cycle, glycolysis, sphingolipid metabolism and tryptophan metabolism, and the toxicity of Brodifacoum is characterized of accumulation effect. The metabonomic method based on urine HPLC-TOF-MS can provide a novel insight into the study on molecular mechanism of Brodifacoum-induced toxicity.
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Plasma metabolic profiling analysis of toxicity induced by Brodifacoum using metabonomics coupled with multivariate data analysis
Forensic science international, 2016Co-Authors: Hui Yan, Bao-hua Shen, Ping Xiang, Zheng Qiao, Min ShenAbstract:Brodifacoum is one of the most widely used rodenticides for rodent control and eradication; however, human and animal poisoning due to primary and secondary exposure has been reported since its development. Although numerous studies have described Brodifacoum induced toxicity, the precise mechanism still needs to be explored. Gas chromatography mass spectrometry (GC-MS) coupled with an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was applied to characterize the metabolic profile of Brodifacoum induced toxicity and discover potential biomarkers in rat plasma. The toxicity of Brodifacoum was dose-dependent, and the high-dose group obviously manifested toxicity with subcutaneous hemorrhage. The blood Brodifacoum concentration showed a positive relation to the ingestion dose in toxicological analysis. Significant changes of twenty-four metabolites were identified and considered as potential toxicity biomarkers, primarily involving glucose metabolism, lipid metabolism and amino acid metabolism associated with anticoagulant activity, nephrotoxicity and hepatic damage. MS-based metabonomics analysis in plasma samples is helpful to search for potential poisoning biomarkers and to understand the underlying mechanisms of Brodifacoum induced toxicity.
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determination of bromadiolone and Brodifacoum in human blood using lc esi ms ms and its application in four superwarfarin poisoning cases
Forensic Science International, 2012Co-Authors: Hui Yan, Ping Xiang, Lin Zhu, Min ShenAbstract:Superwarfarin poisoning is a growing health problem. A sensitive and reproducible LC-ESI/MS/MS (liquid chromatography electrospray ionization tandem mass spectrometry) method was developed and validated for the determination of bromadiolone and Brodifacoum, the most commonly used superwarfarins, in human blood using warfarin-D5 as an internal standard. Bromadiolone and Brodifacoum were extracted from whole blood samples by liquid-liquid extraction with ethyl acetate. Multiple-reaction monitoring (MRM) was used to detect bromadiolone and Brodifacoum using precursor→product ion combinations of m/z 525→250 and 521→135, respectively. The calibration curves were linear (r(2)=0.9999) in the concentration range of 0.5-100.0 ng/mL for bromadiolone and Brodifacoum, with a lower limit of detection of 0.1 and 0.2 ng/mL, respectively, in whole blood. This method detected trace levels of bromadiolone and Brodifacoum in whole blood samples and can be used in the diagnosis of poisoned human beings.
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Determination of bromadiolone and Brodifacoum in human blood using LC-ESI/MS/MS and its application in four superwarfarin poisoning cases
Forensic Science International, 2012Co-Authors: Hui Yan, Ping Xiang, Lin Zhu, Min ShenAbstract:Superwarfarin poisoning is a growing health problem. A sensitive and reproducible LC-ESI/MS/MS (liquid chromatography electrospray ionization tandem mass spectrometry) method was developed and validated for the determination of bromadiolone and Brodifacoum, the most commonly used superwarfarins, in human blood using warfarin-D5 as an internal standard. Bromadiolone and Brodifacoum were extracted from whole blood samples by liquid-liquid extraction with ethyl acetate. Multiple-reaction monitoring (MRM) was used to detect bromadiolone and Brodifacoum using precursor→product ion combinations of m/z 525→250 and 521→135, respectively. The calibration curves were linear (r(2)=0.9999) in the concentration range of 0.5-100.0 ng/mL for bromadiolone and Brodifacoum, with a lower limit of detection of 0.1 and 0.2 ng/mL, respectively, in whole blood. This method detected trace levels of bromadiolone and Brodifacoum in whole blood samples and can be used in the diagnosis of poisoned human beings.
Philippe Berny - One of the best experts on this subject based on the ideXlab platform.
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accumulation of anticoagulant rodenticides chlorophacinone bromadiolone and Brodifacoum in a non target invertebrate the slug deroceras reticulatum
Science of The Total Environment, 2018Co-Authors: Hussein Alomar, Michael Coeurdassier, Andre Chabert, Philippe BernyAbstract:Abstract Anticoagulant rodenticides (ARs) are used worldwide to control populations of agricultural and urban rodents, but these pesticides may be accumulated in and poisoned non-target species of wildlife. Slugs may feed on rodenticide bait following field applications. Thus, it can be assumed that their predators are exposed to rodenticides through food chain transfer. However, AR exposure in the slugs has not been systematically studied. We investigated the accumulation of three ARs (chlorophacinone, bromadiolone or Brodifacoum) in the slug Deroceras reticulatum exposed for a period of 5 days followed by depuration time of 4 days in the laboratory. Moreover, we studied the exposure of slugs to Brodifacoum in the field. In the laboratory exposure, the slugs consumed rodenticide baits, but no mortality was observed. After 1 day, their concentrations were stable over the time and no differences were detected between the concentrations of the three ARs. After 5 days of exposure, mean concentrations in slugs were 1.71, 1.91 and 0.44 mg/kg wet weight for chlorophacinone, bromadiolone and Brodifacoum respectively. A significant decrease of bromadiolone and Brodifacoum in slugs was observed in the post exposure period. In the field study, Brodifacoum was detected in > 90% of analyzed slugs after application of Brodifacoum baits. Then, based on a toxicity-exposure ratio approach, we found that slug consumption may represent a risk of secondary poisoning for three of their predators under acute, repeated or subchronic exposure scenarios. These results suggest that the slugs are not only the potential subject to primary exposure, but also the source of secondary exposure for their predators following application of rodenticide baits.
Hui Yan - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of Brodifacoum-induced Toxicity by Metabonomics Approach Based on HPLC-TOF-MS
Fa yi xue za zhi, 2017Co-Authors: Hui Yan, Xian-yi Zhuo, Bao-hua Shen, Ping Xiang, Min ShenAbstract:OBJECTIVES To analyse the metabolic changes in urine of rats with Brodifacoum intoxication, and to reveal the molecular mechanism of Brodifacoum-induced toxicity on rats. METHODS By establishing a Brodifacoum poisoning rats model, the urine metabolic profiling data of rats were acquired using high performance liquid chromatography-time of flight mass spectrometry （HPLC-TOF-MS）. The orthogonal partial least squares analysis-discrimination analysis （OPLS-DA） was applied for the multivariate statistics and the discovery of differential metabolites closely related to toxicity of Brodifacoum. RESULTS OPLS-DA score plot showed that the urinary metabolic at different time points before and after drug administration had good similarity within time period and presented clustering phenomenon. Comparing the urine samples of rats before drug administration with which after drug administration, twenty-two metabolites related to Brodifacoum-induced toxicity were selected. CONCLUSIONS The toxic effect of Brodifacoum worked by disturbing the metabolic pathways in rats such as tricarboxylic cycle, glycolysis, sphingolipid metabolism and tryptophan metabolism, and the toxicity of Brodifacoum is characterized of accumulation effect. The metabonomic method based on urine HPLC-TOF-MS can provide a novel insight into the study on molecular mechanism of Brodifacoum-induced toxicity.
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Plasma metabolic profiling analysis of toxicity induced by Brodifacoum using metabonomics coupled with multivariate data analysis
Forensic science international, 2016Co-Authors: Hui Yan, Bao-hua Shen, Ping Xiang, Zheng Qiao, Min ShenAbstract:Brodifacoum is one of the most widely used rodenticides for rodent control and eradication; however, human and animal poisoning due to primary and secondary exposure has been reported since its development. Although numerous studies have described Brodifacoum induced toxicity, the precise mechanism still needs to be explored. Gas chromatography mass spectrometry (GC-MS) coupled with an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was applied to characterize the metabolic profile of Brodifacoum induced toxicity and discover potential biomarkers in rat plasma. The toxicity of Brodifacoum was dose-dependent, and the high-dose group obviously manifested toxicity with subcutaneous hemorrhage. The blood Brodifacoum concentration showed a positive relation to the ingestion dose in toxicological analysis. Significant changes of twenty-four metabolites were identified and considered as potential toxicity biomarkers, primarily involving glucose metabolism, lipid metabolism and amino acid metabolism associated with anticoagulant activity, nephrotoxicity and hepatic damage. MS-based metabonomics analysis in plasma samples is helpful to search for potential poisoning biomarkers and to understand the underlying mechanisms of Brodifacoum induced toxicity.
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determination of bromadiolone and Brodifacoum in human blood using lc esi ms ms and its application in four superwarfarin poisoning cases
Forensic Science International, 2012Co-Authors: Hui Yan, Ping Xiang, Lin Zhu, Min ShenAbstract:Superwarfarin poisoning is a growing health problem. A sensitive and reproducible LC-ESI/MS/MS (liquid chromatography electrospray ionization tandem mass spectrometry) method was developed and validated for the determination of bromadiolone and Brodifacoum, the most commonly used superwarfarins, in human blood using warfarin-D5 as an internal standard. Bromadiolone and Brodifacoum were extracted from whole blood samples by liquid-liquid extraction with ethyl acetate. Multiple-reaction monitoring (MRM) was used to detect bromadiolone and Brodifacoum using precursor→product ion combinations of m/z 525→250 and 521→135, respectively. The calibration curves were linear (r(2)=0.9999) in the concentration range of 0.5-100.0 ng/mL for bromadiolone and Brodifacoum, with a lower limit of detection of 0.1 and 0.2 ng/mL, respectively, in whole blood. This method detected trace levels of bromadiolone and Brodifacoum in whole blood samples and can be used in the diagnosis of poisoned human beings.
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Determination of bromadiolone and Brodifacoum in human blood using LC-ESI/MS/MS and its application in four superwarfarin poisoning cases
Forensic Science International, 2012Co-Authors: Hui Yan, Ping Xiang, Lin Zhu, Min ShenAbstract:Superwarfarin poisoning is a growing health problem. A sensitive and reproducible LC-ESI/MS/MS (liquid chromatography electrospray ionization tandem mass spectrometry) method was developed and validated for the determination of bromadiolone and Brodifacoum, the most commonly used superwarfarins, in human blood using warfarin-D5 as an internal standard. Bromadiolone and Brodifacoum were extracted from whole blood samples by liquid-liquid extraction with ethyl acetate. Multiple-reaction monitoring (MRM) was used to detect bromadiolone and Brodifacoum using precursor→product ion combinations of m/z 525→250 and 521→135, respectively. The calibration curves were linear (r(2)=0.9999) in the concentration range of 0.5-100.0 ng/mL for bromadiolone and Brodifacoum, with a lower limit of detection of 0.1 and 0.2 ng/mL, respectively, in whole blood. This method detected trace levels of bromadiolone and Brodifacoum in whole blood samples and can be used in the diagnosis of poisoned human beings.
Xiao-hong Chen - One of the best experts on this subject based on the ideXlab platform.
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High-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry for the determination of flocoumafen and Brodifacoum in whole blood.
Journal of applied toxicology : JAT, 2006Co-Authors: Micong Jin, Xiao-kun Ouyang, Xiao-hong ChenAbstract:A high-performance liquid chromatographic–tandem mass spectrometric (HPLC–MS–MS) assay was developed and validated to determine quantitatively flocoumafen and Brodifacoum in whole blood using warfarin as an internal standard (IS). Liquid–liquid extraction, using ethyl acetate, was used to isolate flocoumafen, Brodifacoum and the IS from the biological matrix. Detection was performed on a mass spectrometer by negative electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode. The calibration curves were linear (r2 > 0.998) in the concentration range of 0.1–100.0 ng ml−1 with a lower limit of quantification of 0.05 ng ml−1 for flocoumafen, and 0.1 ng ml−1 for Brodifacoum in whole blood. Intra-day and inter-day relative standard deviations (RSDs) were less than 8.0% and 10.8%, respectively. Recoveries of flocoumafen and Brodifacoum ranged from 78.0% to 83.7%. This assay can be used to determine trace flocoumafen and Brodifacoum in whole blood to investigate suspected poisoning of human and animals. Copyright © 2006 John Wiley & Sons, Ltd.
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High-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry for the determination of flocoumafen and Brodifacoum in whole blood.
Journal of applied toxicology : JAT, 2006Co-Authors: Micong Jin, Xiao-kun Ouyang, Xiao-hong ChenAbstract:A high-performance liquid chromatographic-tandem mass spectrometric (HPLC-MS-MS) assay was developed and validated to determine quantitatively flocoumafen and Brodifacoum in whole blood using warfarin as an internal standard (IS). Liquid-liquid extraction, using ethyl acetate, was used to isolate flocoumafen, Brodifacoum and the IS from the biological matrix. Detection was performed on a mass spectrometer by negative electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode. The calibration curves were linear (r(2) > 0.998) in the concentration range of 0.1-100.0 ng ml(-1) with a lower limit of quantification of 0.05 ng ml(-1) for flocoumafen, and 0.1 ng ml(-1) for Brodifacoum in whole blood. Intra-day and inter-day relative standard deviations (RSDs) were less than 8.0% and 10.8%, respectively. Recoveries of flocoumafen and Brodifacoum ranged from 78.0% to 83.7%. This assay can be used to determine trace flocoumafen and Brodifacoum in whole blood to investigate suspected poisoning of human and animals.
Penny Fisher - One of the best experts on this subject based on the ideXlab platform.
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Residue profiles of Brodifacoum in coastal marine species following an island rodent eradication
Ecotoxicology and environmental safety, 2014Co-Authors: Bryce M. Masuda, Penny Fisher, Brent BeavenAbstract:Abstract The second-generation anticoagulant rodenticide Brodifacoum is an effective tool for the eradication of invasive rodents from islands and fenced sanctuaries, for biodiversity restoration. However, broadcast application of Brodifacoum bait on islands may expose non-target wildlife in coastal marine environments to Brodifacoum, with subsequent secondary exposure risk for humans if such marine wildlife is harvested for consumption. We report a case study of monitoring selected marine species following aerial application of Brodifacoum bait in August 2011 to eradicate Norway rats ( Rattus norvegicus ) from Ulva Island, New Zealand. Residual concentrations of Brodifacoum were detected in 3 of 10 species of coastal fish or shellfish sampled 43–176 d after bait application commenced. Residual Brodifacoum concentrations were found in liver, but not muscle tissue, of 2 of 24 samples of blue cod (0.026 and 0.092 µg/g; Parapercis colias ) captured live then euthanized for tissue sampling. Residual Brodifacoum concentrations were also found in whole-body samples of 4 of 24 mussels (range=0.001–0.022 µg/g, n =4; Mytilus edulis ) and 4 of 24 limpets (range=0.001–0.016 µg/g, n =4; Cellana ornata ). Measured residue concentrations in all three species were assessed as unlikely to have eventually caused mortality of the sampled individuals. We also conducted a literature review and determined that in eleven previous accounts of residue examination of coastal marine species following aerial applications of Brodifacoum bait, including our results from Ulva Island, the overall rate of residue detection was 5.6% for marine invertebrates (11 of 196 samples tested) and 3.1% for fish (2 of 65 samples tested). Furthermore, our results from Ulva Island are the first known detection of Brodifacoum residue in fish liver following an aerial application of Brodifacoum bait. Although our findings confirm the potential for coastal marine wildlife to be exposed to Brodifacoum following island rodent eradications using aerial bait application, the risk of mortality to exposed individual fish or shellfish appears very low. There is also a very low risk of adverse effects on humans that consume fish or shellfish containing residual concentrations in the ranges reported here. Furthermore, any Brodifacoum residues that occur in marine wildlife decline to below detectable concentrations over a period of weeks. Thus potential human exposure to Brodifacoum through consumption of marine wildlife containing residual Brodifacoum could be minimized by defining ‘no take’ periods for harvest following bait application and regular monitoring to confirm the absence of detectable residues in relevant marine wildlife.
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anticoagulant rodenticide Brodifacoum detected in dead nestlings of an insectivorous passerine
2014Co-Authors: Bryce M. Masuda, Penny Fisher, Ian G JamiesonAbstract:The anticoagulant rodenticide Brodifacoum is widely used to eradicate invasive rats from islands for the protection and restoration of populations of native species. However, Brodifacoum is also highly toxic to birds. We report the first apparent case of secondary Brodifacoum exposure and subsequent poisoning in nestlings of an insectivorous passerine, the Stewart Island robin (Petroica australis rakiura). Thirteen dead nestlings were collected 3-4 months after Brodifacoum bait was applied to eradicate rats from Ulva Island, New Zealand. Twelve of these composite nestling samples contained moderate concentrations of Brodifacoum (mean = 0.08 ± 0.02 µg g -1 ; range = 0.011-0.28 µg g -1 ) at levels comparable with those associated with mortality in adult birds of other species (0.2 µg g -1 in liver), which suggests exposure in the robin nestlings was lethal. However, we were unable to determine the definitive cause(s) of death because sampling of dead nestlings was opportunistic and we were unable to test live nestlings for residue as a comparison. The period between Brodifacoum application and mortality in the nestlings (52-92 days) implicates secondary poisoning. Our results highlight the potential role of invertebrates as vectors of anticoagulant rodenticides in the environment, as well as the need for further research on this exposure pathway.
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Accidental discharge of Brodifacoum baits into a freshwater lake: a case study.
Bulletin of environmental contamination and toxicology, 2011Co-Authors: Penny Fisher, L. E. Brown, E. Funnell, A. Fairweather, M. CampionAbstract:Approximately 700 kg of cereal bait containing 20 ppm of the anticoagulant rodenticide Brodifacoum was spilled into a southern New Zealand lake in 2010 from a helicopter being used to transport containers of Brodifacoum bait for an aerial baiting operation. In the month after the spill no residual Brodifacoum was detected in samples of lake water, sediment, benthic invertebrates, eels, and two birds.
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diagnosing the cause of failure to eradicate introduced rodents on islands Brodifacoum versus diphacinone and method of bait delivery
2011Co-Authors: John P Parkes, Penny Fisher, Guy ForresterAbstract:SUMMARY Two types of anticoagulant rodenticides have proven successful at eradicating invasive rats and mice from islands. Brodifacoum is the most commonly used and has a low failure rate both when delivered from the air and from ground-based systems. It does , however, present a risk to non-target animals suc h as birds. When such risk is not acceptable or canno t be mitigated, diphacinone has been favoured by some managers because it is less toxic to birds and less persistent in rodents. However, unlike Brodifacoum, diphacinone requires a rodent to eat s everal baits over several days to ingest a lethal d ose. This increases the risk that not all rodents will b e killed. When data on attempts to eradicate rats a nd mice for both aerial and ground-based methods are c ombined, Brodifacoum has a significantly lower failure rate at 17% (54 of 322 attempts) than dipha cinone at 33% (13 of 39 attempts). The difference i s more significant when just rats are considered. Gro und-based methods show similar failure rates for both rodenticides, but to date the very few attempt s using aerially sown diphacinone baits have had a high failure rate compared with that for brodifacou m.
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Anticoagulant Residues in Non-Target Wildlife – Assessing Sublethal Exposure to Brodifacoum without Lethal Sampling
Proceedings of the Vertebrate Pest Conference, 2010Co-Authors: Penny Fisher, Alan Shlosberg, Leslie Brown, Geoff WrightAbstract:Author(s): Fisher, Penny; Shlosberg, Alan; Brown, Leslie; Wright, Geoff | Abstract: Residues of Brodifacoum and other second-generation anticoagulant rodenticides are reported worldwide in a range of non-target wildlife, especially predatory or scavenging birds and mammals. Determination of exposure to Brodifacoum in such cases relies on analysis of liver tissue. This limits current monitoring efforts to either destructive sampling of live birds or mammals to obtain liver, but more commonly opportunistic post-mortem liver sampling from carcasses in suitable condition. Also, detection of Brodifacoum in liver often cannot be confirmed as a contributor to mortality, and within a potential ‘sublethal’ concentration range the toxicological significance of its presence is uncertain. We sought to determine whether dried blood spot (DBS) sampling could form the basis of a non-lethal, minimally invasive method for determining sublethal exposure to Brodifacoum in live birds. Validation of a method for detecting Brodifacoum in DBS samples, and preliminary comparison of Brodifacoum concentrations in DBS and plasma samples, are described.
