Development of an Ecofriendly Anticoagulant Rodenticide Based on the Stereochemistry of Difenacoum

Damin-Pernik, Marlène; Espana, Bernadette; Besse, Stéphane; Fourel, Isabelle; Caruel, Hervé; Popowycz, Florence; Benoît, Etienne; Lattard, Virginie

doi:10.1124/dmd.116.071688

Cited by 33 publications

(40 citation statements)

References 34 publications

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“…Therefore, commercial second-generation ARs are a mixture of two diastereoisomeric forms (1R,3R)(1S,3S)-isomers and (1R,3S)(1S,3R)-isomers with diferent pharmacokinetic properties. For each second-generation AR, there is systematically one diastereoisomeric form with a shorter half-life than the other one (Table 1) [20,27]. Proportion between stereoisomers in commercial baits is deined by regulatory documents.…”

Section: Pharmacokinetics Propertiesmentioning

confidence: 99%

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Poisoning by Anticoagulant Rodenticides in Humans and Animals: Causes and Consequences

Lefebvre¹,

Fourel²,

Queffélec³

et al. 2017

Poisoning - From Specific Toxic Agents to Novel Rapid and Simplified Techniques for Analysis

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Anticoagulant rodenticides (ARs) are a keystone of the management of rodent populations in the world. The widespread use of these molecules raises questions on exposure and intoxication risks, which deine the safety of these products. Exposures and intoxications can afect humans, domestic animals and wildlife. Consequences are diferent for each group, from the simple issue of intoxication in humans to public health concern if farm animals are exposed. After a rapid presentation of the mechanism of action and the use of anticoagulant rodenticides, this chapter assesses the prominence of poisoning by anticoagulant rodenticides in humans, domestic animals and wildlife.

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Section: Pharmacokinetics Propertiesmentioning

confidence: 99%

“…Therefore, some recent research makes efort to implement a third generation of ARs which is based on the stereochemistry concept, which would be eicient against resistant strains of rodents and be less persistent and thus less involved in secondary poisoning [20,27].…”

Section: Prevention Of Poisoningmentioning

confidence: 99%

Poisoning by Anticoagulant Rodenticides in Humans and Animals: Causes and Consequences

Lefebvre¹,

Fourel²,

Queffélec³

et al. 2017

Poisoning - From Specific Toxic Agents to Novel Rapid and Simplified Techniques for Analysis

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“…Line 114.-123 ….." it was proposed by Damin et al, (2016, 2017) 2016, 2017) proposed lowering to lower the proportion of the most persistent isomer (trans-bromadiolone) to produce obtain a new bait with the same ability to kill rodents (because both isomers have identical toxicity) but with decreased ecological risk for predators (because cis-bromadiolone is less persistent in tissue). This proposal was hypothesis is based on pharmacological data from of laboratory and wild rats (Damin et al, 2016(Damin et al, , 2017Fourel et al, 2017), although while the pharmacokinetics of SGARs diastereoisomers in for other species (other rodents and non-targetspecies) is unknown. The persistence of isomers and their respective proportions in other rodents and predators with secondary exposure should be evaluated before modification of the actual baits is instituted."…”

Section: Responses To Reviewers Commentsmentioning

confidence: 99%

“…Suggest rephrase to "…. difenacoum in their body (Damin-Pernik et al, 2016Fourel et al, 2017). Proportions of the minor isomers cis-bromadiolone and trans-difenacoum (minor isomers) in the livers liver of rats were very different…."…”

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confidence: 99%

Cis-bromadiolone diastereoisomer is not involved in bromadiolone Red Kite ( Milvus milvus) poisoning

Fourel

Damin-Pernik

Benoît

et al. 2017

Science of The Total Environment

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Anticoagulant rodenticides (ARs) are widely used pesticides to control rodent populations. Bromadiolone, a second generation anticoagulant rodenticide (SGARs), is authorized in France to control the population of water voles (Arvicola scherman). The persistence of SGARs in rodents is responsible for secondary exposure or poisoning of predators and scavengers, and is of ecological concern for the conservation of endangered species. Commercial formulations are a mixture of two diastereoisomers of bromadiolone: 70-90% is trans-bromadiolone and 10-30% is cis-bromadiolone. Both diastereoisomers have been shown to inhibit coagulation function with the same potency. On the other hand, cis-bromadiolone has been shown to be less tissue-persistent than transbromadiolone in rats. This difference led to residue levels in rats with substantially weakened proportion in cis-bromadiolone compared to the composition of baits. In this study, a multi-residue LC-MS/MS method for the quantification of the diastereoisomers of SGARs was used to investigate their proportions in field samples of predators. In 2011, 28 red kites (Milvus milvus) were found dead within a few months of bromadiolone application in grassland to control water vole outbreaks. In this study, we report the concentrations of the two diastereoisomers of bromadiolone measured in the livers of thirteen red kites. Exposure to bromadiolone was apparent in all the kites with hepatic concentrations of trans-bromadiolone ranging from 390 to 870 ng/g (89 to 99% of summed SGARs). However, cisbromadiolone was not detected in 5 of 13 red kites and was present at very low concentrations (below 2.2ng/g) in 8 of 13 kites, demonstrating that cis-bromadiolone is not involved in this red kite poisoning event.The results suggest that a change of the proportions of bromadiolone diastereoisomers in baits could reduce the risk of secondary poisoning of predators, but retain primary toxicity for control rodent outbreaks.Response to Reviewers: May 31, 2017 Dear Daniel A. Wunderlin Thank you for your remarks on our manuscript entitled « Cis-bromadiolone diastereoisomer is not involved in bromadiolone Red Kite (Milvus milvus) poisoning» by Fourel et al. We carefully re-revised the manuscript to address the reviewers' concerns. Specific responses to each question are given below. Reviewers/Editor comments:Reviewer #2: This is a re-review of a paper that I reviewed previously. The manuscript that has been resubmitted is much improved and I believe the authors have satisfactorily addressed or rebutted the reviewers' comments. The paper presents important novel data on how isomer composition may alter the risk of secondary poisoning from SGARs.Although the grammar and language are much improved on the original ms, there is still some improvement that is necessary. I have split my comments on this into two parts on the attached pdf, the first that covers small scale questions re meaning where language has been ambiguous to some extent and needs clarification, the second are simply sug...

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“…On the other hand, SGAR molecules have two asymmetric carbons and each of them can be in R or S configuration . Thus, SGAR molecules exist as four stereoisomers with asymmetric carbons ( i.e ., C1 and C3) being in R/R, R/S, S/R or S/S configuration.…”

Section: A Way To Improve Ar Molecules: Their Stereoisomerismmentioning

confidence: 99%

The stereoisomerism of second generation anticoagulant rodenticides: a way to improve this class of molecules to meet the requirements of society?

Lattard

Benoît

2018

Pest Management Science

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Second generation anticoagulant rodenticides (SGAR) are generally highly efficient for rodent management even towards warfarin-resistant rodents. Nevertheless, because of their long tissue-persistence, they are very associated with non-target exposure of wildlife and have been identified as 'Candidates for Substitution' by the European Union's competent authority. A promising way to reduce ecotoxicity issues associated to SGAR could be the improvement of SGAR based on their stereoisomery, and due to this improvement, positioning about SGAR might be reconsidered. © 2018 Society of Chemical Industry.

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Development of an Ecofriendly Anticoagulant Rodenticide Based on the Stereochemistry of Difenacoum

Cited by 33 publications

References 34 publications

Poisoning by Anticoagulant Rodenticides in Humans and Animals: Causes and Consequences

Poisoning by Anticoagulant Rodenticides in Humans and Animals: Causes and Consequences

Cis-bromadiolone diastereoisomer is not involved in bromadiolone Red Kite ( Milvus milvus) poisoning

The stereoisomerism of second generation anticoagulant rodenticides: a way to improve this class of molecules to meet the requirements of society?

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