This review outlines the current knowledge on the use of enrofloxacin in veterinary medicine from biochemical mechanisms to the use in the field conditions and even resistance and ecotoxicity. The basics of biochemistry, the mechanisms of action and resistance and pharmacokinetics are presented. Then an overview of available veterinary products, their efficacy and their toxicity against target species, human and environment is provided.

Second-generation anticoagulant rodenticides (SGARs) have been used since the 1980s for pest management. They are highly efficient even in warfarin-resistant rodents. Nevertheless, because of their tissue persistence, nontarget poisoning by SGARs is commonly described in wildlife. Due to this major problem, a new generation of anticoagulants must be developed to limit this risk. This study proposes a method of developing a new generation of anticoagulant rodenticides by revisiting the old SGARs based on the concept of stereochemistry. Each current SGAR is a mixture of diastereomers. Diastereomers of each compound were purified, and their biologic properties were compared by determining their ability to inhibit vitamin K epoxide reductase (VKOR) activity involved in the activation of vitamin K-dependent clotting factors and their toxicokinetic properties. Systematically, for each SGAR, both diastereomers are as effective in inhibiting VKOR activity. However, their toxicokinetic properties are very different, with one of the two diastereomers always more rapidly cleared than the other one. For all SGARs except flocoumafen, the less persistent diastereomer is always the less predominant isomer present in the current mixture. Therefore, the development of baits containing only the less persistent diastereomer would avoid the ecotoxicological risk associated with their use without decreasing their efficacy.

Two distinguishable chemotypes of Ferula communis have been described: the 'nonpoisonous' chemotype, containing as main constituents the daucane esters; and the 'poisonous' chemotype containing prenylated coumarins, such as ferulenol and ferprenin. Ferulenol and ferprenin are 4-oxygenated molecules such as dicoumarol and warfarin, the first developed antivitamin K molecules. Antivitamin K molecules specifically inhibit VKORC1, an enzyme essential for recycling vitamin K. This latest is involved in the activation of clotting factors II, VII, IX, X. The inhibiting effect of ferulenol on VKORC1 was shown in rat, but not for species exposed to F. communis while in vivo studies suggest differences between animal susceptibility to ferulenol. The inhibiting effect of ferprenin on VKORC1 was never demonstrated. The aim of this study was to compare the inhibiting effect of both compounds on VKORC1 of different species exposed to F. communis. Vitamin K epoxide activity was evaluated for each species from liver microsomes and inhibiting effect of ferulenol and ferprenin was characterized. Ferulenol and ferprenin were shown to be able to inhibit VKORC1 from all analyzed species. Nevertheless, susceptibility to ferulenol and ferprenin presented differences between species, suggesting a different susceptibility to 'poisonous' chemotypes of F. communis.

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.

Vitamin K antagonists are used as rodenticides for pest control management. In rodents, prothrombin time is used to monitor their effect despite its limits and the emergence of many coagulation methods. The aim of this study is to explore different coagulation monitoring methods in order to propose the best method and the best parameter to monitor vitamin K antagonists effect in rodents.The coagulation function was thus monitored with global coagulation assays and specialty assays after difethialone administration in rats.Despite many parameters obtained by thromboelastometry, only clotting time and clot formation time obtained by ExTEM were modified. Their evolution was fast with doubling time 1 respectively of 4.0h and 3.7h but their increases were delayed with a lag time higher than 8h.Conversely, prothrombin time evolution presented a lag time of only 2h, but a higher doubling time of 7.2h. The measurements of factor VII and X activities were the most sensitive assays to monitor vitamin K antagonists effect with almost no lag time and the fastest evolution.Nevertheless, factor X was shown to be the only key factor driving prothrombin time.Monitoring factor X activity enables to follow most effectively the anticoagulation status in rats after rodenticides administration.

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The current management of rodent pest populations is based on second-generation anticoagulant rodenticides (SGAR). These molecules, of which difethialone is part, are much more efficient than the first generation. Nevertheless, this efficiency comes with a major drawback, SGARs are tissue-persistent that increases the exposure of rodent predators to them. According to its chemical structure, difethialone has four stereoisomers, whose specific inhibition potency and pharmacokinetic have never been described and might be useful to design new eco-friendly rodenticides. The study aimed to investigate the ability to inhibit anticoagulant target enzyme (VKORC1) and the pharmacokinetics in rats of the four difethialone stereoisomers in rats. We show that stereoisomers are all highly efficient to inhibit VKORC1 activity, but they have distinct initial half-life with 6.0h, 25.4h, 69.3h and 82.3h for respectively E4-trans, E2-cis, E1-trans andE3-cis stereoisomer. These results open the way of the development of eco-friendly and efficient rodenticide by mixing some of these stereoisomers. Preferential incorporation of the E4-trans stereoisomer (high inhibitory VKORC1 potency, relatively shorter liver half-life) into difethialone rodenticides baits might produce a more eco-friendly product than current commerciallyavailable difethialone formulations. In addition, we put forward modeling to help design bait according to the circumstance of use (presence of non-target species, food competition, etc) by modulating the theoretical AUC and the theoretical concentration of the product at the death of the rodent pest. Thus, this modeling might allow to diminish the use of laboratory animal in assay.