To protect native wildlife, more than one hundred rodent eradications have been attempted in the Mediterranean islands by using anticoagulant rodenticides (ARs). Despite their high efficiency, resistance to ARs has been observed in many countries and it is mostly related to missense mutations (SNPs) in the VKORC1 gene. The presence of resistant individuals reduces the efficiency of rodent management, leading to an excessive use of ARs. Thus, the risk of poisoning in non-target species increases. In this study, the first survey of ARs resistance in the house mouse Mus domesticus covering multiple islands in the Mediterranean was performed. Tissue samples of eighty-two mice from eleven islands in Italy were analysed and eight missense SNPs were found. In addition to some well-known missense mutations, such as Tyr139Cys, six new missense SNPs for the house mouse were discovered, four of which were new even for any rodent species. Furthermore, the frequency of Tyr139Cys significantly increased in Ventotene Island after a four-year long rat eradication. This could be due to the selective pressure of ARs that allowed the mice carrying the mutation to survive. This study demonstrates once again the importance of assessing resistance to ARs before undertaking rodent eradications. Indeed, this would allow an informed decision of the most effective AR to use, maximizing the success rate of the eradications and minimizing secondary poisoning and other deleterious effects for non-target species and the environment.

The Natal multimammate mouse (Mastomys natalensis) is the host of Lassa mammarenavirus, causing Lassa haemorrhagic fever in West Africa. As there is currently no operational vaccine and therapeutic drugs are limited, we explored rodent control as an alternative to prevent Lassa virus spillover in Upper Guinea, where the disease is highly endemic in rural areas. In a seven-year experiment, we distributed rodenticides for 10-30 days once a year and, in the last year, added intensive snap trapping for three months in all the houses of one village. We also captured rodents both before and after the intervention period to assess their effectiveness by examining alterations in trapping success and infection rates (Lassa virus RNA and IgG antibodies). We found that both interventions reduced the rodent population by 74-92% but swiftly rebounded to pre-treatment levels, even already six months after the last snap-trapping control. Furthermore, while we observed that chemical control modestly decreased Lassa virus infection rates annually (a reduction of 5% in seroprevalence per year), the intensive trapping unexpectedly led to a significantly higher infection rate (from a seroprevalence of 28% before to 67% after snap trapping control). After seven years, we conclude that annual chemical control, alone or with intensive trapping, is ineffective and sometimes counterproductive in preventing Lassa virus spillover in rural villages. These unexpected findings may result from density-dependent breeding compensation following culling and the survival of a small percentage of chronically infected rodents that may spread the virus to a new susceptible generation of mice.

Anticoagulant rodenticides (ARs) have caused widespread contamination and poisoning of predators and scavengers. The diagnosis of toxicity proceeds from evidence of hemorrhage, and subsequent detection of residues in liver. Many factors confound the assessment of AR poisoning, particularly exposure dose, timing and frequency of exposure, and individual and taxon-specific variables. There is a need, therefore, for better AR toxicity criteria. To respond, we compiled a database of second-generation anticoagulant rodenticide (SGAR) residues in liver and postmortem evaluations of 951 terrestrial raptor carcasses from Canada and the United States, 1989 to 2021. We developed mixed-effects logistic regression models to produce specific probability curves of the toxicity of ∑SGARs at the taxonomic level of the family, and separately for three SGARs registered in North America, brodifacoum, bromadiolone, and difethialone. The ∑SGAR threshold concentrations for diagnosis of coagulopathy at 0.20 probability of risk were highest for strigid owls (15 ng g-1) lower and relatively similar for accipitrid hawks and eagles (8.2 ng g-1) and falcons (7.9 ng g-1), and much lower for tytonid barn owls (0.32 ng g-1). These values are lower than those we found previously, due to compilation and use of a larger database with a mix of species and source locations, and also to refinements in the statistical methods. Our presentation of results on the family taxonomic level should aid in the global applicability of the numbers. We also collated a subset of 440 single-compound exposure events and determined the probability of SGAR-poisoning symptoms as a function of SGAR concentration, which we then used to estimate relative SGAR toxicity and toxic equivalence factors: difethialone, 1, brodifacoum, 0.8, and bromadiolone, 0.5. Environ Toxicol Chem 2024;43:988-998. © 2024 His Majesty the King in Right of Canada and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC Reproduced with the permission of the Minister of Environment and Climate Change Canada.

The use of anticoagulant rodenticides (ARs) is one of the most commonly employed management methods for pest rodents. ARs compete with vitamin K (VK) required for the synthesis of blood clotting factors in the liver, resulting in inhibition of blood coagulation and often animal death due to hemorrhage. Besides rodents (target species), ARs may affect non-target animal species and humans. Out of hemostasis disturbance, the effects of ARs may be related to the inhibition of proteins that require VK for their synthesis but are not involved in the coagulation process, to their direct cytotoxicity, and their pro-oxidant/proinflammatory activity. A survey of the cellular and molecular mechanisms of these sublethal/asymptomatic AR effects is given in this review. Data from field, clinical, and experimental studies are presented. Knowledge of these mechanisms might improve hazard characterization and identification of potential ecotoxicological risks associated with ARs, contributing to a safer use of these chemicals.

Rodent management involves the use of anticoagulant rodenticides (ARs). This use has resulted in the selection of numerous resistance alleles in the Vkorc1 gene, encoding the target enzyme of ARs. In Africa, although rodents are a major problem as a consequence of their transport and transmission of zoonotic pathogens, and damage to crops, the use of ARs and the spread of resistance alleles are poorly documented. We attempted to address both issues in Chad which is one of the largest countries in Africa. Owing to its location at the crossroads of central and northern Africa, Chad is representative of many African countries.
METHODS: Using a sampling of nearly 300 rodents composed of invasive and endemic rodents collected in six of Chad\'s largest cities, exposure to ARs was analyzed by their quantification in the liver; the spread of AR resistance alleles was analyzed by Vkorc1 sequencing.
RESULTS: We demonstrate the use of both ARs generations in Chadian cities and report the total sequencing of the Vkorc1 for 44 Mastomys natalensis with detection of two different haplotypes, the sequencing of the Vkorc1 for two other endemic rodent species, M. kollmannspergeri and Arvicanthis niloticus, and finally the detection of three new missense mutations - V29E, V69E and D127V - in R. rattus, potentially associated with resistance to ARs.
CONCLUSIONS: These results should argue for the implementation of a reasoned management of rodent populations in Africa to avoid the spread of ARs resistance alleles. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Anticoagulant rodenticides (ARs) are used to control pest rodent species but can result in secondary poisoning of non-target animals, especially raptors. In the present study, differences in AR sensitivity among avian species were evaluated by comparing in vivo warfarin pharmacokinetics and effects, measuring cytochrome P450s (CYPs) expression involved in AR metabolism, and conducting in vitro inhibition assays of the AR target enzyme Vitamin K 2,3-epoxide reductase (VKOR). Oral administration of warfarin at 4 mg/kg body weight did not prolong prothrombin time in chickens (Gallus gallus), rock pigeons (Columba livia), or Eastern buzzards (Buteo japonicus). Rock pigeons and buzzards exhibited shorter plasma half-life of warfarin compared to chickens. For the metabolite analysis, 4\'-hydroxywarfarin was predominantly detected in all birds, while 10-hydroxywarfarin was only found in pigeons and raptors, indicating interspecific differences in AR metabolism among birds likely due to differential expression of CYP enzymes involved in the metabolism of ARs and variation of VKOR activities among these avian species. The present findings, and results of our earlier investigations, demonstrate pronounced differences in AR sensitivity and pharmacokinetics among bird species, and in particular raptors. While ecological risk assessment and mitigation efforts for ARs have been extensive, AR exposure and adverse effects in predatory and scavenging wildlife continues. Toxicokinetic and toxicodynamic data will assist in such risk assessments and mitigation efforts.

Anticoagulant rodenticide (AR) exposure in wild carnivores is a current and global concern due to continuous and widespread use worldwide. We studied the prevalence of ARs in liver samples of 25 red foxes (Vulpes vulpes), 3 European badgers (Meles meles) and 2 genets (Genneta genneta) from Alicante (Spanish Levante region) obtained in 2021 and 2022. In addition to trauma, poisoning by pesticides is the most frequent cause of death in wild carnivores in this region. The present research aims to explain a possible association between the fact of suffering from an infectious disease and the increase in ARs concentrations in the affected animals. Both first- and second-generation ARs were analysed by HPLC/MS/TOF in liver samples. Apart from the cause of death, the influence of other variables such as age, sex and body weight were also assessed on AR liver concentrations. Potential health risks for individuals and populations in the study area have also been studied. Our research detected higher AR concentrations in the group of red foxes clinically diagnosed with infectious disease compared to the group of apparently healthy red foxes, mostly killed by trauma. Furthermore, our results lead us to suggest that red fox could be considered a good sentinel species for the risk of exposure to ARs in other wild mammals. All the livers analysed contained ARs and the most detected compounds in red fox were difenacoum, bromadiolone, brodifacoum, present in all the samples analysed, and flocoumafen (in 96 %). Additionally, 53 % of the animals had at least one second generation anticoagulant rodenticide (SGAR) above the threshold value reported as triggering adverse health effects (200 ng/g). Regarding this, the level of risk in red fox in this area might be classified as high and worrying. Moreover, we suggest that individuals and populations with weakened health due to other diseases (for example, infectious or parasitic diseases) might be more prone to high exposure to anticoagulant rodenticides and, very probably, would be more sensitive to suffering serious effects at lower doses of ARs.

Anticoagulant rodenticides (AR) have been used globally to manage commensal rodents for decades. However their application has also resulted in primary, secondary, and tertiary poisoning in wildlife. Widespread exposure to ARs (primarily second generation ARs; SGARs) in raptors and avian scavengers has triggered considerable conservation concern over their potential effects on populations. To identify risk to extant raptor and avian scavenger populations in Oregon and potential future risk to the California condor (Gymnogyps californianus) flock recently established in northern California, we assessed AR exposure and physiological responses in two avian scavenger species (common ravens [Corvus corax] and turkey vultures [Cathartes aura]) throughout Oregon between 2013 and 2019. AR exposure was widespread with 51% (35/68) of common ravens and 86% (63/73) of turkey vultures containing AR residues. The more acutely toxic SGAR brodifacoum was present in 83% and 90% of AR exposed common ravens and turkey vultures. The odds of AR exposure in common ravens were 4.7-fold higher along the coastal region compared to interior Oregon. For common ravens and turkey vultures that were exposed to ARs, respectively, 54% and 56% had concentrations that exceeded the 5% probability of toxicosis (>20 ng/g ww; Thomas et al., 2011), and 20% and 5% exceeded the 20% probability of toxicosis (>80 ng/g ww; Thomas et al., 2011). Common ravens exhibited a physiological response to AR exposure with fecal corticosterone metabolites increasing with sum ARs (ΣAR) concentrations. Both female common raven and turkey vultures\' body condition was negatively correlated with increasing ΣAR concentrations. Our results suggest avian scavengers in Oregon are experiencing extensive AR exposure and the newly established population of California condors in northern California may experience similar AR exposure if they feed in southern Oregon. Understanding the sources of ARs across the landscape is an important first step in reducing or eliminating AR exposure in avian scavengers.

Anticoagulant rodenticides (ARs), particularly second-generation compounds (SGAR), are known to be a potential threat to unintended species due to their tissue persistence. The liver is the storage tissue of ARs and is a matrix of choice in diagnosing exposure and intoxication of non-target fauna. However, it is only available on dead animals. Blood and faeces can be used on living animals. These two biological matrices were compared in terms of their relevance to exposure to ARs. In addressing this question, we compared the faecal, plasma and liver concentrations of bromadiolone, one of the SGAR frequently implicated in wildlife exposure. We studied this comparison at the individual level and at the population level, considering three influencing factors: dose, sex and time. Our findings demonstrate that faecal analyses are more valuable than plasma analyses for monitoring AR exposure of domestic and wild animals, even if faecal concentrations cannot be correlated with liver concentrations.

The widespread use of second-generation anticoagulant rodenticides (SGARs) and their high persistence in animal tissues has led to these compounds becoming ubiquitous in rodent-predator-scavenger food webs. Exposure to SGARs has usually been investigated in wildlife species found dead, and despite growing evidence of the potential risk of secondary poisoning of predators and scavengers, the current worldwide exposure of free-living scavenging birds to SGARs remains scarcely investigated. We present the first active monitoring of blood SGAR concentrations and prevalence in the four European obligate (i.e., vultures) and facultative (red and black kites) avian scavengers in NE Spain. We analysed 261 free-living birds and detected SGARs in 39.1% (n = 102) of individuals. Both SGAR prevalence and concentrations (ΣSGARs) were related to the age and foraging behaviour of the species studied. Black kites showed the highest prevalence (100%), followed by red kites (66.7%), Egyptian (64.2%), bearded (20.9%), griffon (16.9%) and cinereous (6.3%) vultures. Overall, both the prevalence and average ΣSGARs were higher in non-nestlings than nestlings, and in species such as kites and Egyptian vultures foraging in anthropic landscapes (e.g., landfill sites and livestock farms) and exploiting small/medium-sized carrions. Brodifacoum was most prevalent (28.8%), followed by difenacoum (16.1%), flocoumafen (12.3%) and bromadiolone (7.3%). In SGAR-positive birds, the ΣSGAR (mean ± SE) was 7.52 ± 0.95 ng mL-1; the highest level detected being 53.50 ng mL-1. The most abundant diastereomer forms were trans-bromadiolone and flocoumafen, and cis-brodifacoum and difenacoum, showing that lower impact formulations could reduce secondary exposures of non-target species. Our findings suggest that SGARs can bioaccumulate in scavenging birds, showing the potential risk to avian scavenging guilds in Europe and elsewhere. We highlight the need for further studies on the potential adverse effects associated with concentrations of SGARSs in the blood to better interpret active monitoring studies of free-living birds.