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1.
Proc Natl Acad Sci U S A ; 115(51): 13033-13038, 2018 12 18.
Article in English | MEDLINE | ID: mdl-30509996

ABSTRACT

Mass mortalities of honey bees occurred in France in the 1990s coincident with the introduction of two agricultural insecticides, imidacloprid and fipronil. Imidacloprid, a neonicotinoid, was widely blamed, but the differential potency of imidacloprid and fipronil has been unclear because of uncertainty over their capacity to bioaccumulate during sustained exposure to trace dietary residues and, thereby, cause time-reinforced toxicity (TRT). We experimentally quantified the toxicity of fipronil and imidacloprid to honey bees and incorporated the observed mortality rates into a demographic simulation of a honey bee colony in an environmentally realistic scenario. Additionally, we evaluated two bioassays from new international guidance for agrochemical regulation, which aim to detect TRT. Finally, we used analytical chemistry (GC-MS) to test for bioaccumulation of fipronil. We found in demographic simulations that only fipronil produced mass mortality in honey bees. In the bioassays, only fipronil caused TRT. GC-MS analysis revealed that virtually all of the fipronil ingested by a honey bee in a single meal was present 6 d later, which suggests that bioaccumulation is the basis of TRT in sustained dietary exposures. We therefore postulate that fipronil, not imidacloprid, caused the mass mortalities of honey bees in France during the 1990s because it is lethal to honey bees in even trace doses due to its capacity to bioaccumulate and generate TRT. Our results provide evidence that recently proposed laboratory bioassays can discriminate harmful bioaccumulative substances and, thereby, address evident shortcomings in a regulatory system that had formerly approved fipronil for agricultural use.


Subject(s)
Bees/drug effects , Bees/growth & development , Insecticides/toxicity , Mortality , Pesticides/toxicity , Pyrazoles/toxicity , Animals , Toxicity Tests
2.
Pest Manag Sci ; 72(10): 1897-900, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26750092

ABSTRACT

BACKGROUND: Concentrations of the neonicotinoid insecticides clothianidin, thiamethoxam and imidacloprid were determined in honey collected in Spring 2013 from a variety of locations in England. The honey was produced before the moratorium in the EU on the use of neonicotinoids in pollinator-attractive crops became effective. RESULTS: Neither imidacloprid nor its metabolites were detected in any honey samples. Concentrations of clothianidin ranged from <0.02 to 0.82 µg kg(-1) , and thiamethoxam concentrations were between <0.01 and 0.79 µg kg(-1) . CONCLUSION: Neonicotinoid concentrations were below those likely to cause any chronic mortality. The concentrations detected should provide a useful baseline against which the effectiveness of the moratorium in reducing exposure of honeybees can be measured. © 2016 Society of Chemical Industry.


Subject(s)
Honey/analysis , Insecticides/analysis , Animals , Bees , England , Environmental Monitoring , Guanidines/analysis , Imidazoles/analysis , Neonicotinoids , Nitro Compounds/analysis , Oxazines/analysis , Pesticide Residues/analysis , Thiamethoxam , Thiazoles/analysis
3.
Pest Manag Sci ; 70(12): 1780-4, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24888990

ABSTRACT

BACKGROUND: Concentrations of the neonicotinoid insecticides clothianidin, thiamethoxam and imidacloprid were determined in arable soils from a variety of locations in England. RESULTS: In soil samples taken from the central area of fields, concentrations of clothianidin ranged from 0.02 to 13.6 µg kg(-1) . Thiamethoxam concentrations were between <0.02 and 1.50 µg kg(-1) , and imidacloprid concentrations between <0.09 and 10.7 µg kg(-1) . Concentrations of clothianidin and thiamethoxam were lower in soil samples taken from the edges of fields than from the centres of fields, but this difference was less pronounced for imidacloprid. CONCLUSION: This work gives a clear indication of the levels of neonicotinoids in arable soils after typical use of these compounds as seed dressings in the United Kingdom. There was evidence that imidacloprid was more persistent in the soils studied than clothianidin and thiamethoxam. As clothianidin and thiamethoxam have largely superseded imidacloprid in the United Kingdom, neonicotinoid levels were lower than suggested by predictions based on imidacloprid alone.


Subject(s)
Insecticides/analysis , Pesticide Residues/analysis , Soil Pollutants/analysis , England , Guanidines/analysis , Imidazoles/analysis , Neonicotinoids , Nitro Compounds/analysis , Oxazines/analysis , Thiamethoxam , Thiazoles/analysis
4.
Cell Stem Cell ; 8(2): 149-63, 2011 Feb 04.
Article in English | MEDLINE | ID: mdl-21295272

ABSTRACT

Women with inherited mutations in the BRCA1 gene have increased risk of developing breast cancer but also exhibit a predisposition for the development of aggressive basal-like breast tumors. We report here that breast epithelial cells derived from patients harboring deleterious mutations in BRCA1 (BRCA1(mut /+) give rise to tumors with increased basal differentiation relative to cells from BRCA1+/+ patients. Molecular analysis of disease-free breast tissues from BRCA1(mut /+) patients revealed defects in progenitor cell lineage commitment even before cancer incidence. Moreover, we discovered that the transcriptional repressor Slug is an important functional suppressor of human breast progenitor cell lineage commitment and differentiation and that it is aberrantly expressed in BRCA1(mut /+) tissues. Slug expression is necessary for increased basal-like phenotypes prior to and after neoplastic transformation. These findings demonstrate that the genetic background of patient populations, in addition to affecting incidence rates, significantly impacts progenitor cell fate commitment and, therefore, tumor phenotype.


Subject(s)
Breast Neoplasms/metabolism , Genetic Predisposition to Disease/genetics , Stem Cells/cytology , Adult , Animals , Breast Neoplasms/genetics , Female , Flow Cytometry , Genes, BRCA1 , Humans , Immunohistochemistry , Mice , Mice, SCID , Middle Aged , Molecular Sequence Data , Phenotype , Reverse Transcriptase Polymerase Chain Reaction , Snail Family Transcription Factors , Stem Cells/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
5.
J Chromatogr A ; 1141(1): 117-22, 2007 Feb 02.
Article in English | MEDLINE | ID: mdl-17184785

ABSTRACT

An analytical method employing clean up by high-performance gel permeation chromatography (HPGPC) and solid-phase extraction (SPE) on Florisil cartridges was developed to determine residues of eleven imidazole and triazole ergosterol-biosynthesis-inhibiting (EBI) fungicides in honeybee samples. Detection was by means of gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring (SIM) mode. The method was validated by fortifying control samples at levels of 0.01 and 0.05 micro g/bee. Mean recoveries for each analyte except imazalil were between 79 and 99% with relative standard deviations of 12.3% or less. Mean recoveries of imazalil were 51% at 0.01 micro g/bee and 81% at 0.05 micro g/bee. Limits of detection for the analytes investigated ranged from 0.005 to 0.001 micro g/bee.


Subject(s)
Bees/chemistry , Fungicides, Industrial/analysis , Gas Chromatography-Mass Spectrometry , Imidazoles/analysis , Pesticide Residues/analysis , Triazoles/analysis , Animals , Electrons , Solutions
6.
J Agric Food Chem ; 54(5): 1588-93, 2006 Mar 08.
Article in English | MEDLINE | ID: mdl-16506805

ABSTRACT

This study describes a generic biological screening assay designed to detect anticoagulant rodenticides based on their inhibitory action on the vitamin K epoxide reductase protein complex, resulting in an accumulation of under-carboxylated prothrombin or proteins induced by vitamin K antagonism (PIVKA-II). A combined cell culture/ELISA assay was optimized to measure PIVKA-II production by the human hepatoma HepG2 cell line cultured in the presence of anticoagulant rodenticides. The specificity and sensitivity of the assay was validated using 41 grain extracts containing representative concentrations of rodenticide or appropriate nonrodenticide control compounds. In all cases, PIVKA-II produced by HepG2 cells in response to grain extracts spiked with rodenticides was detected by ELISA, while PIVKA-II was not detected in supernatants collected from cells exposed to nonrodenticide controls. This represents a novel, class-specific biological assay for the detection of anticoagulant rodenticides present in contaminated grain.


Subject(s)
Anticoagulants/analysis , Biological Assay , Edible Grain/chemistry , Enzyme-Linked Immunosorbent Assay/methods , Indans/pharmacology , Rodenticides/analysis , Anticoagulants/pharmacology , Biomarkers/analysis , Carcinoma, Hepatocellular , Cell Line, Tumor , Coumarins/analysis , Coumarins/pharmacology , Food Contamination/analysis , Humans , Indans/analysis , Liver Neoplasms , Organophosphates/pharmacology , Protein Precursors/analysis , Protein Precursors/biosynthesis , Prothrombin/analysis , Prothrombin/biosynthesis , Warfarin/analysis , Warfarin/pharmacology
7.
J AOAC Int ; 88(1): 204-20, 2005.
Article in English | MEDLINE | ID: mdl-15759743

ABSTRACT

The United Kingdom Wildlife Incident Investigation Scheme (WIIS) investigates cases of suspected poisoning of wildlife, honey bees, and companion animals by pesticides. Together with field inquiries and veterinary post-mortem examinations, the analytical procedures presented here provide a comprehensive approach to the investigation of these cases. The paper covers selection of animal tissues for analysis and methods suitable for the analysis of honey bees and for various types of bait. Seven multiresidue methods cover around 130 pesticides, and methods are also described for a further 8 compounds. These methods are currently used on samples submitted to the Scheme in England and Wales.


Subject(s)
Chemistry Techniques, Analytical/methods , Chromatography, Gas/methods , Chromatography, Liquid/methods , Chromatography/methods , Environmental Pollutants/poisoning , Mass Spectrometry/methods , Pesticides/poisoning , Aluminum/chemistry , Animals , Animals, Wild , Anticoagulants/pharmacology , Bees , Carbamates/analysis , Chromatography, Gas/instrumentation , Chromatography, Gel , Chromatography, Liquid/instrumentation , Environmental Pollutants/analysis , Gizzard, Non-avian/drug effects , Isoxazoles , Liver/drug effects , Mass Spectrometry/instrumentation , Organophosphates/toxicity , Organophosphonates/chemistry , Pesticide Residues/analysis , Pesticide Residues/poisoning , Poisoning/diagnosis , Poisoning/veterinary , Silica Gel , Silicon Dioxide/chemistry , Stomach/drug effects , Tetrazoles , United Kingdom
8.
Proc Biol Sci ; 271 Suppl 6: S458-60, 2004 Dec 07.
Article in English | MEDLINE | ID: mdl-15801603

ABSTRACT

Recent declines in the populations of three species of vultures in the Indian subcontinent are among the most rapid ever recorded in any bird species. Evidence from a previous study of one of these species, Gyps bengalensis, in the Punjab province of Pakistan, strongly implicates mortality caused by ingestion of residues of the veterinary non-steroidal anti-inflammatory drug diclofenac as the major cause of the decline. We show that a high proportion of Gyps bengalensis and G. indicus found dead or dying in a much larger area of India and Nepal also have residues of diclofenac and visceral gout, a post-mortem finding that is strongly associated with diclofenac contamination in both species. Hence, veterinary use of diclofenac is likely to have been the major cause of the rapid vulture population declines across the subcontinent.


Subject(s)
Bird Diseases/epidemiology , Bird Diseases/pathology , Diclofenac/poisoning , Environmental Exposure , Gout/veterinary , Poisoning/veterinary , Animals , Bird Diseases/mortality , Diclofenac/analysis , Falconiformes , Gout/etiology , India/epidemiology , Poisoning/complications , Poisoning/epidemiology , Poisoning/pathology , Population Dynamics
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