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1

Daniells, Laura J. "The non-target effects of anticoagulant rodenticides." Thesis, University of Reading, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559253.

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The exposure of primary and secondary non-target species to Second Generation Anticoagulant Rodenticides (SGARs) is widespread and is a cause for concern amongst conservationists. Levels found in wild non-target species range from trace amounts to lethal levels and occur in up to 81% of barn owl carcasses surveyed. The harm caused by low level AR residues carried by many animals in the wild is not well understood, as is the relative toxicity of the different AR compounds to bird species. My experimental work investigated both sub-lethal residues carried by laboratory mice, Mus musculus, and the comparative toxicity of three SGARs (bromadiolone, difenacoum and brodifacoum) to feral pigeon, Columba livia. Laboratory mice were given >LDso doses of three SGAR compounds and were maintained initially with vitamin K supplements. These mice were monitored for 175 days post-dosing, including through pregnancy. No measurable effect of carrying a SGAR-residue was seen on the growth and breeding activity of mice. Using blood-clotting response testing in pigeons, an EDso was determined for SGAR compounds. Bromadiolone was the least toxic compound to pigeons while the toxicity of difenacoum did not differ significantly from brodifacoum. Data from field trials conducted against AR-resistant rat populations was modelled to compare the exposure levels posed by three SGAR compounds used to control the wild rat infestations. The model was in two parts, the uptake and persistence in the rat population, and the secondary exposure posed by the trials. The AR-resistant rat populations were not controlled completely by bromadiolone or difenacoum and this resulted in much higher levels of SGAR entering the food chain through the rats. This in turn led to higher exposure levels in the secondary non-target species. The need for understanding the toxicity level of each compound to the non-target species of concern was highlighted by this work.
2

Butler, Sarah Elizabeth. "The sub-lethal effects of second generation anticoagulant rodenticides on birds." Thesis, University of Leicester, 2014. http://hdl.handle.net/2381/29133.

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There are high economic, human health and environmental reasons for using Second Generation Anticoagulant Rodenticides (SGARs) but there is also widespread non-target exposure to a large number of bird of prey species, such as red kites and barn owls. My overall aim was to assess the potential biochemical and physiological impacts of sub-lethal exposure on birds. I determined environmentally realistic doses of two SGARs, brodifacoum (high acute toxicity) and difenacoum (most widely used and detected in wildlife), in a model species, Japanese quail (Coturnix coturnix japonica), and used these doses in subsequent studies. Anticoagulation profiles and liver residues associated with the doses were characterised. Unexpectedly, one dose (0.4 mg kg-1 body weight brodifacoum) induced persistent (> three weeks) residual anticoagulation. Half-life and repeat-exposure studies highlighted the risk to birds from multiple exposures of brodifacoum in particular. Liver half lives in quail were longer than in rats for brodifacoum but shorter for difenacoum. The magnitude and duration of anticoagulation was greatly increased by multiple exposures involving brodifacoum and was the result of a complex interplay (including inhibition of binding and replacement) between residues in the liver. Studies on quail chicks demonstrated that, while chicks were not especially sensitive to SGARs, exposure reduced growth by 5-10%. Overall, my results suggest that the most likely exposure scenario for UK wildlife, that of repeated exposures to difenacoum, is likely to pose relatively little increased risk compared to single exposures. This is not true for brodifacoum, but it is less widely used in the UK. Thus, exposure scenarios likely to be associated with greater risk, such as repeated exposures to brodifacoum or mixed exposure patterns, are probably less common in the UK. This may partially explain why the number of detected rodenticide-induced wildlife mortalities is low.
3

Mahjoub, Tarek. "Etudes des propriétés toxicocinétiques et toxicodynamiques des anticoagulants antivitamines K et leurs impacts environnementaux chez les espèces animales non-cibles." Electronic Thesis or Diss., Lyon 1, 2023. https://n2t.net/ark:/47881/m6x34xkf.

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Les rodenticides anticoagulants (AR) constituent un moyen incontournable pour lutter contre les rongeurs nuisibles. L'utilisation écoresponsable des AR tend à limiter l'exposition des espèces non-cibles. Aucune étude sur la prévalence des AR chez les animaux n'a été menée en Tunisie. De ce fait, une première enquête toxicologique a montré que les AR sont incriminés parmi les causes les plus fréquentes d'intoxications aigues aux AR chez le chien. De plus, dans une autre étude, nous avons rapporté que les anticoagulants naturels, comme le férulénol produit par Ferula communis peut causer de lourdes pertes chez les éleveurs locaux. Peu d'études se sont intéressées à la toxicocinétique des AR. Pour évaluer la prévalence d'exposition, le choix de la matrice biologique est primordial et constitue un garant de la robustesse de la méthode utilisée. Le foie est le tissu de stockage des AR et constitue le meilleur prélèvement pour mettre en évidence une exposition chez les animaux. Cependant, ce prélèvement n'est disponible que sur les animaux morts. Par ailleurs, le sang et les fèces peuvent être utilisés sur des animaux vivants. Nous avons étudié la comparaison des trois matrices (foie, sang et fèces), en tenant compte de trois facteurs d'influence : la dose, le sexe et le temps. Nos résultats démontrent que les prélèvements fécaux sont plus utiles que les prélèvements plasmatiques pour le suivi de l'exposition aux AR des animaux domestiques et sauvages. Le tableau clinique lors d'une intoxication aigue aux AR est spectaculaire, cependant, les expositions à faibles doses passent inaperçues mais présentent des effets délétères insidieux sur la santé. L'exposition asymptomatique des animaux domestiques aux AR est peu documentée. Notre étude a montré une prévalence limitée chez les chiens et les chats, contrairement à d'autres travaux où la prévalence chez les prédateurs de la faune sauvage est bien supérieure et dont les analyses ont été réalisés sur les foies d'animaux morts de manière opportuniste, sans tenir compte des animaux sains. Ce travail pourrait générer des idées pour de nouvelles stratégies analytiques et permettrait de mieux aborder les particularités toxicocinétiques et toxicodynamiques chez d'autres espèces non-cibles dans le cadre du développement de nouvelles molécules d'AR plus écoresponsables
Anticoagulant rodenticides (AR) are an essential tool for controlling rodent pests. The environmentally responsible use of AR tends to limit the exposure of non-target species. No study on the prevalence of AR in animals has been conducted in Tunisia. Therefore, a first toxicological survey showed that AR are incriminated as one of the most frequent causes of acute AR poisoning in dogs. Moreover, in another study, we reported that natural anticoagulants, such as ferulenol produced by Ferula communis can cause heavy losses to local farmers. Few studies have focused on the toxicokinetics of AR. To monitor these exposure rates, the validation of the appropriate biological matrix is essential and is a major guarantee of the robustness of the analytical method. The liver is the storage tissue for AR and is the best sample for assessing exposure in animals. However, it is only available from dead animals. Blood and feces can be used from live animals. We studied the comparison of the three matrices (liver, blood, and feces), considering three influencing factors: dose, sex, and time. Our results show that fecal samples are more valuable than plasma samples for monitoring AR exposure in domestic and wild animals. The clinical symptoms of acute AR poisoning are dramatic, but low-dose exposures go unnoticed and present insidious deleterious health effects. Asymptomatic exposure of domestic animals to AR is poorly documented. Our study showed limited prevalence in dogs and cats, in contrast to other work where prevalence in wildlife predators is much higher from analyses performed on the livers of opportunistically dead animals, without considering the healthy ones. This work could generate ideas for new analytical strategies. It would allow better addressing toxicokinetic and toxicodynamic properties in other non-target species as part of the development of new, more eco-friendly AR molecules
4

Fisher, P. M. "Residual concentrations and persistence of the anticoagulant rodenticides brodifacoum and diphacinone in fauna." Lincoln University, 2009. http://hdl.handle.net/10182/930.

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Brodifacoum is a highly effective anticoagulant rodenticide that presents a secondary hazard to some non-target wildlife. The high acute toxicity of brodifacoum to mammals and birds, and its prolonged persistence in liver predicates secondary risk to predators and scavengers of poisoned rodents. Hence there is a need to improve ability to monitor and predict hazards of brodifacoum to non-targets, and optimise use patterns accordingly. Use of a less persistent anticoagulant rodenticide, diphacinone, is an alternative approach currently under investigation in New Zealand. This thesis describes a series of laboratory and pen studies that address information gaps relevant to the assessment of non-target hazards in continued use of brodifacoum, and of using diphacinone as an alternative. Non-lethal techniques for determining sublethal brodifacoum exposure in birds was investigated in chickens. Elevation of prothrombin time was a less reliable index than residual concentrations in tissues. Samples requiring less invasive procedures, such as dried blood spots or faeces, have potential to detect recent sublethal brodifacoum exposure and refinement of these indices could be useful in proactive monitoring of avian wildlife. Residual brodifacoum in eggs of sublethally-exposed hens raised further questions regarding wider non-target hazard and adverse effects on development of fertile eggs or chicks. A laboratory trial with rats found a positive correlation between residual brodifacoum concentrations in liver and the amount of brodifacoum ingested as bait. An estimated 14-22% of ingested brodifacoum was excreted in rat faeces in the period between ingestion of a lethal dose and death, indicating another potentially significant environmental pathway for brodifacoum transfer. In considering diphacinone as a less persistent alternative rodenticide to brodifacoum, evaluation of residual concentrations and persistence in pig tissues was required to estimate secondary hazard to human consumers and adequate with-holding periods for hunting feral pigs in areas where diphacinone was applied. A pen trial showed that domestic pigs were more susceptible to diphacinone toxicity, and thus primary poisoning risk, than previously estimated. Hepatic half-life of diphacinone in pigs was approximately 14 days, indicating reduced persistence in comparison to brodifacoum and enabling estimates of with-holding periods for hunting feral pigs from areas where diphacinone baits were applied. To investigate potential hazards of diphacinone use to invertebrates a trial using tree weta, a native New Zealand invertebrate, was undertaken. Weta readily ate diphacinone wax block baits with no mortality or weight loss evident, indicating low susceptibility. Residual whole-body diphacinone concentrations did not increase with the amount of diphacinone bait eaten. A simple, deterministic risk assessment suggested that, as a single secondary exposure, the maximum diphacinone concentration measured in weta would present a low risk to non-target birds. Given international recognition of the high secondary hazard and corresponding restrictions on use of brodifacoum, continued availability of brodifacoum to non-licensed users and sustained field applications for possum and rodent control in New Zealand is an exceptional use pattern. New data in this thesis suggest that baiting strategies that minimise the amount of brodifacoum available in the environment are important and regulatory review of some New Zealand brodifacoum applications should address this. In parallel, development of diphacinone as an alternative to brodifacoum should continue, as new data here confirms lower persistence in mammalian liver than brodifacoum, and also indicates low toxicity to invertebrates. However further investigation of multiple-exposure hazard and potential sublethal effects of diphacinone on non-target mammals and birds is warranted before extensive and sustained field applications of diphacinone are undertaken.
5

Loureiro, Maria Adelaide Kress Pinto. "Contribuição para o estudo da fuinha (Martes foina) : aspetos ecológicos, morfológicos e toxicológicos de 40 indivíduos provenientes do Centro de Ecologia, Recuperação e Vigilância de Animais Selvagens (CERVAS)." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2017. http://hdl.handle.net/10400.5/14236.

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Dissertação de Mestrado Integrado em Medicina Veterinária
Em Portugal a sensibilização para a biodiversidade que possuímos é ainda escassa, sendo da responsabilidade de cada um termos um papel ativo nesta luta. Com esse intuito desenvolveu-se este trabalho, acerca da fuinha (Martes foina), pretendendo aprofundar-se o conhecimento sobre este pequeno habitante das florestas e meios urbanos do nosso país, caracterizando-o em diferentes parâmetros: desde a sua morfologia, características anatómicas, reprodutoras, alimentares e epidemiológicas, até ao seu papel no ecossistema, inclusive na sua relação com a espécie humana. Esta relação tende a ser tendencionalmente desvantajosa para espécies predadoras de animais considerados pragas, devido ao combate destas últimas com compostos tóxicos não seletivos. Uma das consequências da exposição a estes compostos relaciona-se com intoxicações em doses sub-letais, que podem não ser a principal causa de morte, mas predispor a tal ou ao aumento da morbilidade. Foi com o objetivo de perceber um pouco mais sobre este tipo de efeitos na fuinha (espécie predadora de roedores) que este trabalho foi realizado, com especial incidência nos rodenticidas anticoagulantes. A amostra populacional em estudo inclui 21 amostras de fígado de fuinhas provenientes do Centro de Ecologia, Recuperação e Vigilância de Animais Selvagens (CERVAS) e recolhidas entre os anos de 2009 a 2015. Estas amostras foram analisadas pela técnica da Cromatografia de Camada Fina para deteção de rodenticidas anticoagulantes (RAC) e em nenhuma delas estes compostos foram detetados.
ABSTRACT - SUB-LETHAL SECONDARY INTOXICATIONS BY ANTICOAGULANT RODENTICIDES IN FUINHAS: A RETROSPECTIVE STUDY OF 21 CASES BETWEEN 2009 AND 2015. - In Portugal, the awareness of the biodiversity we have is still scarce, and it is our responsibility to play an active role in this struggle. With this intention, this study was developed on the stone marten (Martes foina), aiming to deepen the knowledge about this small inhabitant of the forests and urban environments of our country, characterizing it in different parameters: morphology, anatomical characteristics, reproduction, diet, epidemiology and their role in the ecosystem, including their relationship with the human species. This relationship tends to be disadvantageous for predatory species of animals considered as pests, due to their combating with non-selective toxic compounds. One of the consequences of these compounds is sub-lethal dose intoxications, which may not be the main cause of death, but predispose to such or increased morbidity. The main goal of this study is to understand a little more about this type of effects in the stone marten (predator species of rodents) that this work was carried out, with special incidence on anticoagulant rodenticides. Thin Layer Chromatography tecnhique was used in 21 liver samples from the Centro de Ecologia, Recuperação e Vigilância de Animais Selvagens (CERVAS) between 2009 and 2015, and no second generation anticoagulant rodenticide was detected in any of the samples.
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6

Jacquot, Marion. "Usage des rodenticides anticoagulants et conséquences en termes d'exposition et d'impact pour les populations de renard roux." Phd thesis, Université de Franche-Comté, 2013. http://tel.archives-ouvertes.fr/tel-00917412.

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Les rodenticides anticoagulants (RA) constituent le principal moyen de lutte contre les rongeurs. L'exposition aux RA du renard roux et l'impact des RA sur les populations de ce prédateur sont étudiés. En France, on distingue un contexte " biocide " (BCD) où les RA sont principalement utilisés près des bâtiments et un contexte " phytopharmaceutique " (PP) où la bromadiolone (un RA) est également utilisée en plein champs contre le campagnol terrestre. La contamination des rongeurs aux RA est mesurée : 5 RA sont détectés en contexte BCD alors que la bromadiolone est la molécule majoritaire en contexte PP ; les espèces de rongeurs non ciblées par les RA étant exposées dans les 2 contextes. L'exposition est maximale chez les espèces ciblées ou celles au mode de vie similaire. L'exposition du renard est évaluée par la mesure des résidus de RA dans des fèces collectées in situ. La bromadiolone est retrouvée dans 97 % des fèces positives et les RA sont plus retrouvés dans les fèces en cas de traitements PP. En contexte PP, le ratio de fèces positives augmente non linéairement avec la surface traitée dans un rayon d'1 km autour des fèces. L'impact des traitements PP sur les populations de renards est évalué (période 2003-2009, département du Doubs). Les indices d'abondance de renard mesurés sur une commune le printemps d'une année n diminuent avec l'augmentation des quantités d'appâts utilisées les années n-1 et n-2. Pendant la période suivie, la mise en place d'une lutte intégrée contre le campagnol terrestre s'est traduite par une diminution des quantités d'AR utilisées et donc par une diminution des impacts sur les populations de renards.
7

Fergusson, D. "The effects of 4-hydroxycoumarin anticoagulant rodenticides on birds and the development of techniques for non-destructively monitoring their ecotoxicological effect." Thesis, University of Reading, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239503.

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Rached, Antoine. "Exploration des pistes de gestion du risque écotoxicologique associé aux anticoagulants antivitamine K utilisés comme rodonticides." Electronic Thesis or Diss., Lyon, 2022. http://www.theses.fr/2022LYSE1077.

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Les anticoagulants antivitamines K (AVKs) constituent actuellement le moyen de lutte chimique le plus efficace contre les infestations de rongeurs dans les zones rurales et urbaines. Pour assurer un effet létal, les AVKs de première génération doivent être ingérés en plusieurs doses pendant plusieurs jours consécutifs. Cependant, cette consommation chronique était à l'origine de l'apparition d'une résistance à ces molécules chez certaines populations de rongeurs commensaux nuisibles, les rendant moins efficaces. Une deuxième génération de rodonticides anticoagulants a été développée pour surmonter cette résistance. Cette génération est plus puissante (une concentration plus faible d’AVK pour induire la mortalité) et a une durée d'action plus longue (persistance plus longue dans l'organe cible). L'intoxication des animaux non-cibles est le principal inconvénient de la deuxième génération. En effet, l'accès direct à l'appât toxique et la consommation de proies empoisonnées peuvent entraîner des expositions de la faune non-cible. Afin de réduire ce risque écotoxicologique des anticoagulants rodonticides, des solutions ont été envisagées notamment la réduction de la concentration des appâts et l’utilisation des isomères d’AVK (la stéréochimie) qui ont déjà démontré un temps de rétention hépatique court avec une efficacité pareille aux molécules AVKs raticides déjà sur le marché. L’objectif principal de ce travail de thèse est d’explorer ces pistes de gestion de ce risque. Nous nous sommes intéressés dans un premier temps à étudier la pertinence des avantages de la stéréochimie dans le contrôle des différentes espèces de rongeurs nuisibles, notamment les rats, les souris et les campagnols terrestres et chez les deux sexes mâles et femelles. Dans un second temps, nous avons comparé l’évolution des résidus d’AVK chez des rats mâles après administration soit d’une dose faible d’AVK, soit d’une dose forte dans un but d’explorer l’effet de la réduction de la concentration des appâts en AVK sur les résidus restants dans le foie. Ces pistes de gestion ont bien montré leur capacité à réduire les résidus des AVKs, responsables de l’intoxication des espèces non-cibles par la consommation de proies empoisonnées
Vitamin K antagonists (VKA) are currently the most effective chemical control of rodent infestations in rural and urban areas. To ensure a lethal effect, first-generation VKA must be ingested in multiple doses over several consecutive days. However, this chronic consumption was responsible for the development of resistance to these molecules in certain populations of commensal rodents, making them less effective. A second generation of anticoagulant rodenticides was developed to overcome this resistance. This generation is more potent (lower concentration of VKA to induce mortality) and has a longer duration of action (longer persistence in the target organ). The intoxication of non-target animals is the main drawback of the second generation. Indeed, direct access to the toxic bait and the consumption of poisoned prey can lead to exposure of non-target fauna. In order to reduce this ecotoxicological risk of rodenticide anticoagulants, some solutions have been considered such as the reduction of bait concentration and the use of VKA isomers (stereochemistry) which have already demonstrated short tissue retention time with an efficiency similar to VKA rodenticide molecules currently available on the market. The main objective of this thesis work is to explore these possibilities for managing this risk. First, we studied the relevance of the benefits of stereochemistry in the control of different species of rodent pests including rats, mice and water voles and in both male and female species. In a second phase, we compared the evolution of VKA residues in male rats after administration of either a low or a high dose of VKA in order to explore the effect of reducing the concentration of VKA baits on the residues remaining in the liver. These management approaches have been shown to reduce the residues of VKA, which are responsible for the intoxication of non-target species through the consumption of poisoned prey
9

Jorge, Ana Patrícia Mestre de Oliveira. "Clínica e cirurgia em animais de companhia: intoxicação por rodenticidas anticoagulantes." Master's thesis, Universidade de Évora, 2015. http://hdl.handle.net/10174/16227.

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O presente relatório de estágio diz respeito às atividades desenvolvidas durante o período de estágio curricular do mestrado integrado em Medicina Veterinária ministrado pela Universidade de Évora. O estágio curricular decorreu no Hospital Veterinário da Arrábida (HVA) durante 6 meses, compreendidos entre 15 de Setembro de 2014 a 15 de Março de 2015, sob orientação da Dr.ª. Margarida Fragoso Costa e coorientação da Dr.ª. Ângela Martins. Este relatório é constituído por um resumo da casuística assistida, por uma monografia subordinada ao tema “Intoxicação por rodenticidas anticoagulantes” e um estudo comparativo de casos clínicos relacionados com o tema da monografia. A intoxicação por rodenticidas anticoagulantes é um dos mais frequentes tipos de intoxicação na clínica de animais de companhia, sendo importante o conhecimento por parte do médico veterinário dos diferentes tipos de rodenticidas existentes, bem como abordagem a esta patologia e ao paciente intoxicado no geral; Abstract: - Small animal medicine and surgery This report aims to describe the activities developed during my curricular internship of my masters in veterinary medicine degree at the University of Évora. The internship took place at the Hospital Veterinário da Arrábida (HVA) with the duration of six months, from 15 September 2014 to 15 March 2015, under the supervision of Dr. Margarida Fragoso Costa and co-supervision of Dr. Ângela Martins. This report consists of a summary of assisted cases, a bibliographic review entitled "Anticoagulant rodenticides poisoning” and a comparative study of clinical cases related to this subject. Poisoning by anticoagulant rodenticides is one of the most frequent types of poisoning in the small animal clinic. It is important for the veterinary to have knowledge of the different types of rodenticides and how to approach this issue, as well as the overall intoxicated patient.
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Chia, Tio-Huat. "Growth, distribution and susceptibility of major rat species to anticoagulant rodenticides and the inheritance of resistance to warfarin in Rattus tiomanicus in oil palm plantations in peninsular Malaysia." Thesis, University of Reading, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342461.

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Corniot, Anne-Gaëlle. "Intoxication par un raticide anticoagulant, la chlorophacinone : mise au point d'une méthode de dosage plasmatique par chromatographie liquide haute performance." Bordeaux 2, 1997. http://www.theses.fr/1997BOR2P098.

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Montagut-Romans, Adrien. "Réactivité et pharmacomodulation de la 4-hydroxycoumarine : conception, synthèse et évaluation biologique de nouvelles molécules rodonticides éco-compatibles." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10028.

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L'usage des pesticides au sein de l'Union européenne est de plus en plus réglementé, et les rodonticides actuellement disponibles sur le marché sont responsables de nombreuses intoxications secondaires chez les prédateurs des rongeurs. Il est donc crucial aujourd'hui de trouver une alternative plus écologique aux molécules commerciales. Les travaux de recherches décrits dans cette thèse s'inscrivent dans ce contexte et présentent la mise au point de nouvelles voies d'accès à des structures coumariniques et leurs études biologiques. La molécule anticoagulante ciblée se devait d'être active sur rats sensibles et résistants, et d'avoir une rémanence faible dans l'organisme. Les synthèses chimiques ont été menées conjointement avec les tests biologiques, conduisant l'ensemble des études de façon convergente vers la production d'un lead. Trois nouveaux outils moléculaires ont été mis au point et ont permis la synthèse et l'évaluation d'un grand nombre de candidats. Les deux premières en catalyse homogène, sous micro-onde, ont permis de réduire le temps réactionnel nécessaire à la synthèse de 4-hydroxycoumarine substituée sur le carbone 3. La troisième méthodologie conduit par une approche séquentielle aux mêmes types de composés à l'échelle du gramme. Cette dernière ouvre également la porte à de nombreuses possibilités réactionnelles permettant d'envisager plus de diversité. Toutes les molécules ont été évaluées in vitro, sur différentes souches d'enzymes VKORC1 et ont offert une meilleure compréhension des interactions enzyme/inhibiteur. Après cette première évaluation, des tests in vivo ont été conduits sur une sélection de composés, et ont apporté des informations cruciales sur les relations structure/activité in vivo et structure/rémanence. Le meilleur composé synthétisé à ce jour semble répondre parfaitement aux différentes contraintes liées au cahier des charges établi initialement qui se basait sur une approche singlefeeding. Une stratégie multifeeding est aujourd'hui envisagée afin de mieux correspondre à la réalité du terrain. Sur la base de celle-ci, le nombre de composés décrit dans ce manuscrit potentiellement utilisable en tant que rodonticide se retrouve largement augmenté
To reduce the ecological impact of pesticides in UE many new legislations were put in place, in other hand, most of secondary intoxications of rodent's predators are due to rodenticides available on the market. That why it’s crucial to find alternative rodenticide more eco-friendly. This work describes optimization of new coumarinics compounds synthesis and their biological studies. The new anticoagulant should be active on wild and mutant rat, and must have a low hepatic persistence in the rat body. Organic syntheses were driven with biological studies and have converged to discover the lead. Three different new molecular tools were optimized and have allowed the synthesis and the evaluation of a large number of candidates. The first two through homogeneous catalysis by using micro-waves have reduced the time needed for the alkylation of 4-hydroxycoumarin on the carbon 3. The third methodology allows the synthesis of same kind of compounds in large scale. This methodology opens news potentials reactions to add structural diversity. All the molecules were evaluated in vitro on different types of VKORC1 and have participated to a better understanding of the enzyme/inhibitor interactions. After this first evaluation, in vivo tests were performed on a selection of candidates, and have brought a crucial structural relationship between structure and in vivo persistence/activity. The best compound produced by now seems to answer at all specifications established linked to the single-feeding strategy. Multiple-feeding strategy is today planned to better correspond to the field reality. On the base of this one the number of candidates usable as rodenticides is increased
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Hussain, Iftikhar. "Susceptibility to anticoagulants and the development of physiological resistance in Rattus norvegicus and Bandicota bengalensis." Thesis, University of Reading, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241975.

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Senzolo, Mara <1982&gt. "Valutazione di marker diagnostici, epidemiologia e nuove prospettive terapeutiche nell' avvelenamento da rodenticidi anticoagulanti nel cane." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6677/1/senzolo_mara_tesi.pdf.

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In Medicina Veterinaria l'avvelenamento da rodenticidi anticoagulanti è conosciuto e studiato ormai da anni, essendo una delle intossicazioni più comunemente riscontrate nelle specie non target. In letteratura si rinvengono numerose pubblicazioni ma alcuni aspetti sono rimasti ancora inesplorati.Questo studio si propone di valutare il processo infiammatorio, mediante le proteine di fase acuta (APPs), in corso di fenomeni emorragici, prendendo come modello reale un gruppo di soggetti accidentalmente avvelenati da rodenticidi anticoagulanti. I 102 soggetti avvelenati presentano un valore più elevato di proteina C reattiva (CRP)con una mediana di 4.77 mg/dl statisticamente significativo rispetto alla mediana delle due popolazioni di controllo di pari entità numerica create con cross match di sesso, razza ed età; rispettivamente 0.02 mg/dl dei soggetti sani e 0.37 mg/dl dei soggetti malati di altre patologie. Inoltre all'interno del gruppo dei soggetti avvelenati un valore di CRP elevato all'ammissione può predisporre al decesso. La proteina C reattiva assume quindi un ruolo diagnostico e prognostico in questo avvelenamento. Un'altra finalità, di non inferiore importanza, è quella di definire una linea guida terapeutica con l'ausilio di biomarker coagulativi e di valutare la sicurezza della vitamina K per via endovenosa: in 73 cani, non in terapia con vitamina k, intossicati da rodenticidi anticoagulanti, i tempi della coagulazione (PT ed aPTT) ritornano nel range di normalità dopo 4 ore dalla prima somministrazione di 5 mg/kg di vitamina k per via endovenosa e nessun soggetto durante e dopo il trattamento ha manifestato reazioni anafilattiche, nessuno dei pazienti ha necessitato trasfusione ematica e tutti sono sopravvissuti. Infine si è valutata l'epidemiologia dell'ingestione dei prodotti rodenticidi nella specie oggetto di studio e la determinazione dei principi attivi mediante cromatografia liquida abbinata a spettrofotometria di massa (UPLC-MS/MS).
Anticoagulant rodenticides (AR) are the most commonly used pesticides. They inhibit vitamin K epoxide reductase stopping vitamin K recycling. This will cause depletion of active coagulation factors II-VII-IX-X potentially leading to spontaneous bleeding. The first aim of this study is to measure acute phase proteins in 102 naturally affected dogs by AR intoxication, included in group 0. Two control populations of 102 randomly healthy (group 1) and sick (group 2) dogs were created and matched to group 0 for age, sex (including neutered status), and breed. In particular C-reactive protein (CRP) concentration was significantly (p<0.001) higher in group 0 (median 4.77 mg/dl) versus group 1 (median 0.02 mg/dl) and group 2(median, 0.37 mg/dl). The inflammatory process associated with hemorrhage is probably responsible for the higher CRP concentration. In group 0,CRP concentration was higher in non survivors vs survivors (p=0.04). CRP may be a useful diagnostic and prognostic marker in dogs with AR intoxication. The second aim of this study is to evaluate time to normalisation of activated partial thromboplastin time (aPPT) and prothrombin time (PT) after 5 mg/kg intravenously(IV) vitamin K treatment in 73 dogs with naturally AR intoxication. Four hours and 8 hours post-vitamin K administration (T4 and T8) a coagulation profile was repeated. There was a significant decrease in aPTT and PT between T0 and T4 (p<0.0001). All 73 dogs survived to discharge, none received blood transfusion or had an adverse reaction to IV vitamin k, and by T4 no dogs showed clinical signs of ongoing of external bleeding. This protocol with IV vitamin K administration seems to be safe and effective in treatment of dogs with naturally occurring AR intoxication. Epidemiology of AR intoxication in dogs and determination of responsible compounds by liquid chromatography tandem mass spectrometry has been also evaluated.
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Senzolo, Mara <1982&gt. "Valutazione di marker diagnostici, epidemiologia e nuove prospettive terapeutiche nell' avvelenamento da rodenticidi anticoagulanti nel cane." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6677/.

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Abstract:
In Medicina Veterinaria l'avvelenamento da rodenticidi anticoagulanti è conosciuto e studiato ormai da anni, essendo una delle intossicazioni più comunemente riscontrate nelle specie non target. In letteratura si rinvengono numerose pubblicazioni ma alcuni aspetti sono rimasti ancora inesplorati.Questo studio si propone di valutare il processo infiammatorio, mediante le proteine di fase acuta (APPs), in corso di fenomeni emorragici, prendendo come modello reale un gruppo di soggetti accidentalmente avvelenati da rodenticidi anticoagulanti. I 102 soggetti avvelenati presentano un valore più elevato di proteina C reattiva (CRP)con una mediana di 4.77 mg/dl statisticamente significativo rispetto alla mediana delle due popolazioni di controllo di pari entità numerica create con cross match di sesso, razza ed età; rispettivamente 0.02 mg/dl dei soggetti sani e 0.37 mg/dl dei soggetti malati di altre patologie. Inoltre all'interno del gruppo dei soggetti avvelenati un valore di CRP elevato all'ammissione può predisporre al decesso. La proteina C reattiva assume quindi un ruolo diagnostico e prognostico in questo avvelenamento. Un'altra finalità, di non inferiore importanza, è quella di definire una linea guida terapeutica con l'ausilio di biomarker coagulativi e di valutare la sicurezza della vitamina K per via endovenosa: in 73 cani, non in terapia con vitamina k, intossicati da rodenticidi anticoagulanti, i tempi della coagulazione (PT ed aPTT) ritornano nel range di normalità dopo 4 ore dalla prima somministrazione di 5 mg/kg di vitamina k per via endovenosa e nessun soggetto durante e dopo il trattamento ha manifestato reazioni anafilattiche, nessuno dei pazienti ha necessitato trasfusione ematica e tutti sono sopravvissuti. Infine si è valutata l'epidemiologia dell'ingestione dei prodotti rodenticidi nella specie oggetto di studio e la determinazione dei principi attivi mediante cromatografia liquida abbinata a spettrofotometria di massa (UPLC-MS/MS).
Anticoagulant rodenticides (AR) are the most commonly used pesticides. They inhibit vitamin K epoxide reductase stopping vitamin K recycling. This will cause depletion of active coagulation factors II-VII-IX-X potentially leading to spontaneous bleeding. The first aim of this study is to measure acute phase proteins in 102 naturally affected dogs by AR intoxication, included in group 0. Two control populations of 102 randomly healthy (group 1) and sick (group 2) dogs were created and matched to group 0 for age, sex (including neutered status), and breed. In particular C-reactive protein (CRP) concentration was significantly (p<0.001) higher in group 0 (median 4.77 mg/dl) versus group 1 (median 0.02 mg/dl) and group 2(median, 0.37 mg/dl). The inflammatory process associated with hemorrhage is probably responsible for the higher CRP concentration. In group 0,CRP concentration was higher in non survivors vs survivors (p=0.04). CRP may be a useful diagnostic and prognostic marker in dogs with AR intoxication. The second aim of this study is to evaluate time to normalisation of activated partial thromboplastin time (aPPT) and prothrombin time (PT) after 5 mg/kg intravenously(IV) vitamin K treatment in 73 dogs with naturally AR intoxication. Four hours and 8 hours post-vitamin K administration (T4 and T8) a coagulation profile was repeated. There was a significant decrease in aPTT and PT between T0 and T4 (p<0.0001). All 73 dogs survived to discharge, none received blood transfusion or had an adverse reaction to IV vitamin k, and by T4 no dogs showed clinical signs of ongoing of external bleeding. This protocol with IV vitamin K administration seems to be safe and effective in treatment of dogs with naturally occurring AR intoxication. Epidemiology of AR intoxication in dogs and determination of responsible compounds by liquid chromatography tandem mass spectrometry has been also evaluated.
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Huang, Andrew Cheng-An. "Barn owl genetics in Western North America : diversity, phylogeographic structure, connectivity, and potential for a genetic basis to anticoagulant rodenticide susceptibility." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/51947.

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The barn owl (Tyto alba) is distributed across much of North America in areas with extensive old-field and grassland habitat. Barn owls are threatened in British Columbia (BC), where the population has declined by 50% in the last 3 decades. I investigated the genetic diversity and phylogeographic patterns of barn owls in western North America, ranging from BC to California, and one eastern population from Pennsylvania. Using 8 polymorphic microsatellite markers (N=126) and ND2 mitochondrial sequences (N=37), I found a high degree of gene flow among the continental sampled regions (global FST = 0.028). The BC mainland population, despite its northwestern geographic peripheral location and ongoing habitat degradation, is not genetically depauperate. However, individuals from Vancouver Island exhibited the lowest genetic diversity of all sampled locations, likely as a result of its insular nature. The low global FST value estimated from this study suggests that their habitat is well connected across North America. Additionally, microsatellite data revealed that the Santa Barbara Island population showed genetic divergence from its continental counterpart. Mitochondrial data, however, demonstrated that this island population is not monophyletic, and thus cannot be designated as an Evolutionarily Significant Unit. Anticoagulant rodenticides (ARs) are pesticides widely employed worldwide to reduce rodent infestations. Avian predators that hunt extensively for small rodents are at risk of secondary poisoning. AR causes internal bleeding by disrupting the Vitamin K cycle, which is essential for blood clotting. Tolerance to AR appears to be highly variable among individuals for any given avian species. I examined whether single point mutations in the CYP2C45 gene are associated with increased or decreased susceptibility to AR in barn owls. I identified a position that showed a heterozygous C/T in one particular individual with low tolerance, whereas all other individuals exhibited a homozygous C. This transversion results in an amino acid substitution from alanine to valine at a conserved region that could potentially have deleterious effects on the function of and structure the protein. However, it is also possible that the CYP2C45 enzyme was not severely affected due to this amino acid change since both alanine and valine are non-polar/hydrophobic.
Forestry, Faculty of
Graduate
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Morin, Marie-Françoise. "Etude de l'impact sur le milieu naturel de la bromadiolone, rodonticide anticoagulant : évolution en milieu aqueux et bioaccumulation sur des organismes terrestres et aquatiques." Poitiers, 1988. http://www.theses.fr/1988POIT2315.

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Sage, Mickaël. "Transfert de bromadiolone (appâts/sols – campagnols de prairie – renards) : Etude environnementale de la persistance et mesure indirecte de l'exposition." Phd thesis, Université de Franche-Comté, 2008. http://tel.archives-ouvertes.fr/tel-00404261.

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Depuis les années 50, les rodenticides anticoagulants sont couramment utilisés pour contrôler les populations de rongeurs commensaux et de prairie. De nombreux empoisonnements de la faune non cible sont répertoriés partout dans le monde. En Europe de l'Ouest notamment, la bromadiolone est utilisée de façon intensive dans les champs. Elle est le seul rodenticide autorisé en France pour contrôler les populations de Campagnol terrestre, Arvicola terrestris Sherman. Ces opérations utilisant des appâts grains de blé enterrés dans le sol sont réalisées à de larges échelles et des dizaines voire des centaines d'empoisonnements secondaires de prédateurs, dont le renard, sont répertoriés chaque année. Cette étude propose d'apporter des éléments de compréhension sur les modalités de son transfert à travers les systèmes biologiques complexes considérés dans leur intégralité.
Le premier objectif a été d'évaluer la variabilité environnementale de la persistance de la bromadiolone dans les appâts en conditions naturelles. Cette persistance dans les galeries de traitement est courte (demi-vie de 3 à 6 jours) et faiblement influencée par les conditions environnementales (type de sol et conditions climatiques). Cependant, elle augmente considérablement lors du stockage des appâts dans des réserves (27
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Lohr, Michael Thomas. "Response of Australian Boobooks (Ninox boobook) to threatening processes across urban, agricultural, and woodland ecosystems." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2019. https://ro.ecu.edu.au/theses/2255.

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The effects of habitat fragmentation on native wildlife can vary depending on the type of land use occurring in the matrix between remaining habitat fragments. I used Australian boobooks (Ninox boobook) in Western Australia to investigate interactions between matrix type and four different potential threatening processes: secondary poisoning by anticoagulant rodenticides (ARs); limitation of juvenile dispersal and impacts on spatial genetic structure; breeding site availability; and infection by the parasite Toxoplasma gondii. I also conducted a literature review on the use and regulation of ARs in Australia and published accounts of non-target impacts in order to contextualise exposure patterns observed in boobooks. The review revealed records of confirmed or suspected poisoning across 37 vertebrate species in Australia. World literature relating to AR exposure in reptiles suggests that they may be less susceptible to AR poisoning than birds and mammals. This relative resistance may create unevaluated risks for wildlife and humans in Australia where reptiles are more abundant than in cooler regions where AR exposure has been studied in greater depth. I analysed AR residues in boobook livers across multiple habitat types. Second generation anticoagulant rodenticides were detected in 72.6% of individuals sampled. Total AR concentration correlated positively with the proportion of urban land use within an area approximately the size of a boobook’s home range centred on the point where the sample was collected. ARs originating in urban habitat probably pose a substantial threat to boobooks and other predatory wildlife species. No spatial genetic structure was evident in boobooks across habitat types. I observed one individual dispersing at least 26km from its natal home range across urban habitat. The apparent permeability of anthropogenically altered landscapes probably explains the lack of spatial genetic structure and is likely related to the observed ability of boobooks to use resources in both urban and agricultural matrices. Boobooks did not appear to be limited by the availability of suitable nesting sites in urban or agricultural landscapes. Occupancy did not change significantly over the duration of the study in remnants provided with artificial nest boxes in either landscape type. However, in one instance, boobooks successfully used a nest box located in an urban bushland. Nest boxes may be a useful management tool in highly-altered areas where natural hollows are unavailable. Toxoplasma gondii seropositivity in boobooks did not vary significantly by landscape type but was more prevalent in individuals sampled during cooler wetter times of year. Risk of exposure due to greater cat abundance in urban and agricultural landscapes may be offset by creation of environmental conditions less favourable to the survival of T. gondii oocysts in soil. Taken together, this body of research demonstrates variation in relationships between different types of habitat fragmentation and threatening processes related to fragmentation. This research also raises questions about how habitat fragmentation is discussed and studied in the context of species which are capable of making extensive use of matrix habitat. I recommend greater consideration of the concept of “usable space” when studying fragmentation impacts in habitat generalists.
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Felício, Laura Almeida. "Estudo de casos suspeitos de intoxicação por rodenticidas anticoagulantes em cães." Master's thesis, 2018. http://hdl.handle.net/10348/8731.

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O recurso a rodenticidas tem sido frequente, desde a antiguidade, como forma de controlar pragas de roedores por todo o mundo. As opções que surgiram nas últimas décadas, como é o caso dos rodenticidas anticoagulantes, preocupam a comunidade veterinária, uma vez que a sua utilização no contexto urbano poderá promover intoxicações em animais como cães e gatos. Quando ocorre uma intoxicação, verifica-se um bloqueio do ciclo da vitamina K, associado à não ativação dos fatores de coagulação inativos dela dependentes e consequente depleção dos fatores funcionais ainda em circulação. Desta forma, o quadro típico apresentado pelos animais é de carácter hemorrágico e os sinais clínicos que surgirão serão, por norma, desta natureza. Uma desvantagem de uma intoxicação desta magnitude prendese com a impossibilidade de a diagnosticar, com certeza irredutível, em meio clínicohospitalar, sendo só possível fazê-lo recorrendo a laboratórios especializados. Quando em meio hospitalar, as provas de coagulação são a ferramenta mais credível para um diagnóstico presuntivo. O tratamento instituído engloba a estabilização do animal, a administração de vitamina K1 e de produtos sanguíneos que contenham os fatores de coagulação dependentes da vitamina K, apesar de haver outras possibilidades de tratamento mais recentes que têm vindo a surgir em medicina veterinária. Quando diagnosticada precocemente, uma intoxicação por rodenticidas anticoagulantes tem um prognóstico muito favorável. No entanto, este prognóstico poderá não ser tão positivo quando associado a limitações económicas ou quando o quadro hemorrágico já comprometeu a estabilidade circulatória do animal, o tratamento poderá não ser eficaz e o animal acabar por não sobreviver
O recurso a rodenticidas tem sido frequente, desde a antiguidade, como forma de controlar pragas de roedores por todo o mundo. As opções que surgiram nas últimas décadas, como é o caso dos rodenticidas anticoagulantes, preocupam a comunidade veterinária, uma vez que a sua utilização no contexto urbano poderá promover intoxicações em animais como cães e gatos. Quando ocorre uma intoxicação, verifica-se um bloqueio do ciclo da vitamina K, associado à não ativação dos fatores de coagulação inativos dela dependentes e consequente depleção dos fatores funcionais ainda em circulação. Desta forma, o quadro típico apresentado pelos animais é de carácter hemorrágico e os sinais clínicos que surgirão serão, por norma, desta natureza. Uma desvantagem de uma intoxicação desta magnitude prendese com a impossibilidade de a diagnosticar, com certeza irredutível, em meio clínicohospitalar, sendo só possível fazê-lo recorrendo a laboratórios especializados. Quando em meio hospitalar, as provas de coagulação são a ferramenta mais credível para um diagnóstico presuntivo. O tratamento instituído engloba a estabilização do animal, a administração de vitamina K1 e de produtos sanguíneos que contenham os fatores de coagulação dependentes da vitamina K, apesar de haver outras possibilidades de tratamento mais recentes que têm vindo a surgir em medicina veterinária. Quando diagnosticada precocemente, uma intoxicação por rodenticidas anticoagulantes tem um prognóstico muito favorável. No entanto, este prognóstico poderá não ser tão positivo quando associado a limitações económicas ou quando o quadro hemorrágico já comprometeu a estabilidade circulatória do animal, o tratamento poderá não ser eficaz e o animal acabar por não sobreviver
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Almeida, Maria Teresa de Jesus Horta de. "Estudo prospetivo observacional de âmbito clínico: descrição de sete casos clínicos em urgências em intoxicações por rodenticidas anticoagulantes." Master's thesis, 2019. http://hdl.handle.net/10437/9549.

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Orientação : João Cardoso Martins ; co-orientação : Ângela Martins
Os rodenticidas anticoagulantes constituem uma das principais causas de intoxicação em animais de companhia. A aplicação de novas técnicas de diagnóstico e terapêuticas, é crucial para uma melhoria mais rápida e eficaz no estado clínico do animal. O objetivo deste estudo foi a implementação de técnicas de diagnóstico e de monitorização mais rigorosas, juntamente com a administração do antídoto (vitamina K1) no dobro da dose clássica administrada, de forma a minimizar as terapêuticas efetuadas para o tratamento das intoxicações por rodenticidas anticoagulantes. Para tal, recorreu-se a uma amostra de sete cães com intoxicação por rodenticidas anticoagulantes crónica. Estes foram submetidos ao protocolo terapêutico (vitamina K1, 5 mg/kg BID, SC nas primeiras 24h de intoxicação, seguido de 5 mg/kg SID, SC/PO nos dois dias seguintes), em regime de internamento, aplicado no Hospital Veterinário da Arrábida. Os resultados obitdos revelaram não ser necessário, em todos os casos de intoxicação, a transfusão de derivados sanguíneos, minimizando assim a aplicação de uma das medidas de tratamento para este tipo de intoxicação. Desta forma, concluiu-se que, uma monitorização rigorosa e aplicação de métodos de diagnóstico ecográficos mais restritos, é uma metodologia eficaz para designar com maior precisão a terapêutica a efetuar, contribuindo para a diminuição da taxa de mortalidade e morbilidade.
Anticoagulant rodenticides are a major cause of intoxication in companion animals. The application of new therapeutics and diagnostic techniques is crucial for a more rapid and effective improvement in the clinical state of the animal. The objective of this study was the implementation of more rigorous diagnostic and monitoring techniques, coupled with the administration of the antidote (vitamin K1) twice the administered dose, in order to minimize the therapeutics performed for the treatment of anticoagulant rodenticide intoxications. To do so, a sample of seven dogs with chronic anticoagulant rodenticide poisoning was used. These were submitted to the therapeutic protocol (vitamin K1, 5 mg/kg, BID, SC, in the first 24h of intoxication, followed by 5 mg/kg, SID, SC/PO on the following two days), in hospitalization, applied at the Veterinary Hospital of Arrábida. The results showed that, in all cases of intoxication blood bank therapy was not necessary, thus minimizing the application of one of the treatment measures for this type of intoxication. Thus, it was concluded that strict monitoring and application of more restricted ultrasound diagnostic methods, is an effective methodology to designate more precisely

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