bromadiolone and difethialone

Superwarfarins, second-generation long-acting anticoagulant rodenticides, are 4-hydroxycoumarin analogues of warfarin that contain a large hydrophobic side chain. These compounds contain two chiral centers and are synthesized for commercial use as two pairs of diastereomer.. To support studies of superwarfarin pharmacokinetics and other efforts to improve clinical care for poisoning victims, a quantitative assay was developed for the measurement of diastereomer of bromadiolone, difenacoum, flocoumafen, brodifacoum, and difethialone in human plasma.. Based on ultrahigh-pressure liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS), this method was validated according to U.S. Food and Drug Administration (FDA) guidelines. Sample preparation involved simple protein precipitation followed by reversed phase UHPLC, which resolved all five pairs of cis/trans diastereomer in less than 10 min. Superwarfarins were measured using negative ion electrospray followed by selected-reaction monitoring on a triple quadrupole mass spectrometer.. Calibration curves covered 3-4 orders of magnitude with linear regression coefficients of >0.999. The lower limits of quantitation were from 0.013 to 2.41 ng/mL, and intra-day and inter-day accuracy and precision coefficients of variation were <12%.. A 10-min UHPLC-MS/MS assay was developed and validated for the separation and quantitative analysis of the pairs of diastereomer of five superwarfarins in human plasma.. This method was used to identify and measure superwarfarins and their cis/trans diastereomers in plasma obtained from patients treated for coagulopathy following consumption of contaminated synthetic cannabinoid products.

Topics: 4-Hydroxycoumarins; Anticoagulants; Chromatography, High Pressure Liquid; Humans; Reproducibility of Results; Rodenticides; Tandem Mass Spectrometry

Anticoagulant rodenticides (ARs) have been used for decades for rodent control worldwide. Research on the exposure of the environment and accumulation of these active substances in biota has been focused on terrestrial food webs, but few data are available on the impact of ARs on aquatic systems and water organisms. To fill this gap, we analyzed liver samples of bream (Abramis brama) and co-located suspended particulate matter (SPM) from the German Environmental Specimen Bank (ESB). An appropriate method was developed for the determination of eight different ARs, including first- and second-generation ARs, in fish liver and SPM. Applying this method to bream liver samples from 17 and 18 sampling locations of the years 2011 and 2015, respectively, five ARs were found at levels above limits of quantifications (LOQs, 0.2 to 2 μg kg

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Aquatic Organisms; Cyprinidae; Environmental Monitoring; Food Chain; Fresh Water; Germany; Liver; Particulate Matter; Rodenticides; Seafood; Water Pollutants, Chemical

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.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Environmental Monitoring; Massachusetts; Pest Control; Raptors; Rodenticides

Second-generation anticoagulant rodenticides (SGARs) are widely used to control rodent pests but exposure and poisonings occur in non-target species, such as birds of prey. Liver residues are often analysed to detect exposure in birds found dead but their use to assess toxicity of SGARs is problematic. We analysed published data on hepatic rodenticide residues and associated symptoms of anticoagulant poisoning from 270 birds of prey using logistic regression to estimate the probability of toxicosis associated with different liver SGAR residues. We also evaluated exposure to SGARs on a national level in Canada by analysing 196 livers from great horned owls (Bubo virginianus) and red-tailed hawks (Buteo jamaicensis) found dead at locations across the country. Analysis of a broader sample of raptor species from Quebec also helped define the taxonomic breadth of contamination. Calculated probability curves suggest significant species differences in sensitivity to SGARs and significant likelihood of toxicosis below previously suggested concentrations of concern (<0.1mg/kg). Analysis of birds from Quebec showed that a broad range of raptor species are exposed to SGARs, indicating that generalised terrestrial food chains could be contaminated in the vicinity of the sampled areas. Of the two species for which we had samples from across Canada, great horned owls are exposed to SGARs to a greater extent than red-tailed hawks and the liver residue levels were also higher. Using our probability estimates of effect, we estimate that a minimum of 11% of the sampled great horned owl population is at risk of being directly killed by SGARs. This is the first time the potential mortality impact of SGARs on a raptor population has been estimated.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Canada; Environmental Monitoring; Environmental Pollutants; Food Chain; Hawks; Liver; Probability; Quebec; Raptors; Rodenticides; Strigiformes

We investigated whether the allocation of rodenticide baiting points to specific structural elements would result in complete rat eradication on livestock farms, as opposed to assigning the baiting points only to places where there were obvious signs of rat activity. The goal was to establish an effective rodent-control program that is easy for untrained persons to conduct.Rat-control strategies were examined on 25 farms in Velen (Muensterland), Germany, where an average of 20% of trapped rats were resistant for bromadiolone according to a blood-clotting response (BCR) test. All farms were investigated for signs of rat activity prior to and after the control measure. Differences in the percentage level of farmer compliance in setting up the baiting points as prescribed were analysed for each type of baiting point and in total, and were compared between the group of farms which achieved complete rat eradication and those which did not. Farms achieving complete eradication had an average of 81% compliance with prescribed control plans, whereas a significantly lower compliance level of only 51% was recorded on farms that did not achieve eradication. A >/=75% level of implementation of the control plan always resulted in complete control success. The new method of bait-point allocation was incorporated into a self-explanatory computer program, which was verified to be effective during a rat-control campaign in the restricted area after an outbreak of classical swine fever near Soltau in northern Germany, in July 2001. This program, which is available on the Internet, enables the creation of individualised rat-control plans, including complete documentation of the control measure.

Topics: 4-Hydroxycoumarins; Agriculture; Animal Husbandry; Animals; Drug Resistance; Environment; Rats; Rodent Control; Rodenticides