Toxicology of chemical biocides: Anticoagulant rodenticides - Beyond hemostasis disturbance.

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.

Evaluation of anticoagulant rodenticide sensitivity by examining in vivo and in vitro responses in avian species, focusing on raptors.

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.

An atypical presentation of anticoagulant rodenticide toxicosis in a dog.

A 5-month-old intact female Australian shepherd dog was referred to our clinic for neurologic signs including ataxia, a head tilt, and altered mentation following consumption of an unidentified rodenticide several days prior to developing clinical signs. A provisional diagnosis of bromethalin toxicosis had been made, given the neurologic signs seen and the general increased use of bromethalin-containing rodenticide products. However, on physical examination, the dog was noted to have scleral hemorrhage and bleeding at the venipuncture sites, which was inconsistent with bromethalin toxicosis. Coagulation testing was supportive of anticoagulant rodenticide toxicosis and the rodenticide was later identified as the first-generation anticoagulant rodenticide diphacinone. The neurologic signs seen were attributed to a coagulopathy causing multifocal hemorrhage into the central nervous system. Neurologic signs rapidly resolved following treatment with a frozen plasma transfusion and vitamin K1. This atypical presentation of an anticoagulant rodenticide toxicosis highlights the need for accurate product identification, if available, and thorough patient examination and laboratory testing. An atypical presentation of anticoagulant rodenticide toxicosis should be considered when neurologic signs are present with clinical bleeding, especially if the type of rodenticide is unknown, or even if it was not thought to have an anticoagulant as the active ingredient. Key clinical message: Given the change in commercially available rodenticide products, this case highlights the need for accurate product identification in cases of suspected toxicosis, and the variable clinical signs that can be seen following anticoagulant rodenticide toxicosis.

Présentation atypique d'une toxicose aux rodenticides anticoagulants chez un chien. Une chienne berger australien intacte âgée de 5 mois a été référée à notre clinique pour des signes neurologiques, notamment de l'ataxie, une inclinaison de la tête et une altération de l'état mental à la suite de la consommation d'un rodenticide non identifié plusieurs jours avant l'apparition des signes cliniques. Un diagnostic provisoire de toxicose à la brométhaline avait été posé, compte tenu des signes neurologiques observés et d'une utilisation historique accrue de produits rodenticides contenant de la brométhaline. Cependant, lors de l'examen physique, il a été constaté que le chien présentait une hémorragie sclérale et des saignements au niveau des sites de ponction veineuse, ce qui n'était pas cohérent avec une toxicose à la brométhaline. Les tests de coagulation ont confirmé la toxicose au rodenticide anticoagulant et le rodenticide a ensuite été identifié comme étant le rodenticide anticoagulant de première génération diphacinone. Les signes neurologiques observés ont été attribués à une coagulopathie provoquant une hémorragie multifocale du système nerveux central. Les signes neurologiques ont rapidement disparu après un traitement par transfusion de plasma congelé et de vitamine K1. Cette présentation atypique d'une toxicose aux rodenticides anticoagulants met en évidence la nécessité d'une identification précise du produit, si disponible, ainsi que d'un examen approfondi du patient et de tests de laboratoire. Une présentation atypique de toxicose des rodenticides anticoagulants doit être envisagée lorsque des signes neurologiques sont présents avec saignement clinique, en particulier si le type de rodenticide est inconnu, ou même si l'on ne pense pas qu'un anticoagulant soit l'ingrédient actif.Message clinique clé :Compte tenu de l'évolution des produits rodenticides disponibles dans le commerce, ce cas met en évidence la nécessité d'une identification précise du produit en cas de suspicion de toxicose et les signes cliniques variables qui peuvent être observés à la suite d'une toxicose au rodenticide anticoagulant.(Traduit par Dr Serge Messier).

Silent killers? The widespread exposure of predatory nocturnal birds to anticoagulant rodenticides.

Anticoagulant rodenticides (ARs) influence predator populations and threaten the stability of ecosystems. Understanding the prevalence and impact of rodenticides in predators is crucial to inform conservation planning and policy. We collected dead birds of four nocturnal predatory species across differing landscapes: forests, agricultural, urban. Liver samples were analysed for eight ARs: three First Generation ARs (FGARs) and five SGARs (Second Generation ARs). We investigated interspecific differences in liver concentrations and whether landscape composition influenced this. FGARs were rarely detected, except pindone at low concentrations in powerful owls Ninox strenua. SGARs, however, were detected in every species and 92 % of birds analysed. Concentrations of SGARs were at levels where potential toxicological or lethal impacts would have occurred in 33 % of powerful owls, 68 % of tawny frogmouths Podargus strigoides, 42 % of southern boobooks N. bookbook and 80 % of barn owls Tyto javanica. When multiple SGARs were detected, the likelihood of potentially lethal concentrations of rodenticides increased. There was no association between landscape composition and SGAR exposure, or the presence of multiple SGARs, suggesting rodenticide poisoning is ubiquitous across all landscapes sampled. This widespread human-driven contamination in wildlife is a major threat to wildlife health. Given the high prevalence and concentrations of SGARs in these birds across all landscape types, we support the formal consideration of SGARs as a threatening process. Furthermore, given species that do not primarily eat rodents (tawny frogmouths, powerful owls) have comparable liver rodenticide concentrations to rodent predators (southern boobook, eastern barn owl), it appears there is broader contamination of the food-web than anticipated. We provide evidence that SGARs have the potential to pose a threat to the survival of avian predator populations. Given the functional importance of predators in ecosystems, combined with the animal welfare impacts of these chemicals, we propose governments should regulate the use of SGARs.

Active metabolite of the neurotoxic rodenticide bromethalin along with anticoagulant rodenticides detected in birds of prey in the northeastern United States.

Little is known about the ecologic fate of the neurotoxic rodenticide bromethalin, which is currently registered for use in the United States, Canada, and other countries including Australia. There is minimal research on bromethalin's potential to cause secondary toxicosis in nontarget wildlife. The aim of this study was to evaluate adipose tissue in four species of birds of prey presented to a wildlife clinic in Massachusetts, USA, for desmethylbromethalin (DMB), the active metabolite of bromethalin. Birds were also screened for anticoagulant rodenticides (ARs) in liver tissue to present a more complete picture of rodenticide exposures in this geographic area and to evaluate the impact of current mitigation measures in place during the time of sampling, 2021-2022. A total of 44 hawks and owls were included; DMB was found in 29.5% of birds and ARs were present in 95.5%. All birds with DMB detections also had residues of ARs. Among birds positive for ARs, 81% had two or more compounds. To the authors' knowledge the data presented here represent the first published monitoring study to document bromethalin/DMB bioaccumulation in obligate carnivores. As DMB is a more potent neurotoxicant than its parent compound, these results are cause for concern and an indication that further monitoring and study of the potential risk of bromethalin to wildlife species is needed. These findings have global implications as increasing concern regarding exposure to and toxicosis from ARs in nontarget wildlife worldwide leads to a search for alternatives and effective mitigation approaches.

Análisis de un protocolo basado en la norma USEPA 1.213 para la evaluación regulatoria de la eficacia de las cebaderas en el control seguro de roedores pequeños / Analysis of a protocol based on the USEPA 1.213 standard for the regulatory evaluation of the efficacy of the bait station system in the safe control of small rodents

Varios rodenticidas modernos son formulados con compuestos anticoagulantes superwarfarínicos. Debido a su alta toxicidad en humanos, los cebos suelen ser formulados con otros ingredientes destinados a generar respuestas de rechazo en el caso de ingestión accidental o intento de suicidio; aun así, las unidades hospitalarias reportan anualmente numerosos casos de intoxicaciones con rodenticidas. Se han desarrollado cebaderas con el propósito de brindar al usuario alta eficacia y seguridad extendida. Dado que en muchos países existe experiencia limitada para la evaluación regulatoria de cebos combinados con cebaderas, en este trabajo se presenta un protocolo adaptado a partir de la guía USEPA- 1.213/1990, el cual se propone para verificar la aptitud de las cebaderas para controlar roedores en ambientes hogareños, ocupacionales y otros espacios urbanos. Se incluye una discusión de aspectos técnicos que se espera que sean de ayuda para los asesores de las agencias regulatorias intervinientes al interpretar los resultados en términos de eficacia y seguridad. El sistema cebadera-cebo examinado mostró alta letalidad en ratas adultas jóvenes. La inspección, carga y recarga de producto fresco se realizó en forma simple, rápida y segura; sólo excepcionalmente se observó dispersión del cebo fuera de la cebadera. Sin embargo, debe tenerse en cuenta que el sistema que solicita un registro ante la autoridad regulatoria debe ser adecuado a la especie que se busca controlar, considerando las diferencias de peso corporal entre ratas y ratones, entre machos y hembras, y entre animales jóvenes y adultos, lo cual determina la facilidad de ingreso al interior del dispositivo (cebadera) donde se coloca el cebo contenido en su embalaje unitario original. (AU)

Several modern rodenticides are formulated with anticoagulant superwarfarin compounds. Due to their high toxicity in humans, these baits are usually formulated with other ingredients intended to generate rejection responses in the case of accidental ingestion or suicide attempt. However, hospital units report numerous cases of poisoning with rodenticides every year. Box-like bait stations have been developed to provide the user with high efficacy and extended safety. Given that in many countries there is limited experience for the regulatory consideration of bait stations, this work presents a protocol adapted from the USEPA-1.213/1990 guideline, proposed to verify the aptitude of these devices to control wild rodents in home, work, and other urban spaces. The work includes a discussion of technical issues that are expected to be helpful to advisors of the regulatory agencies involved in interpreting the results in terms of efficacy and safety. The bait-station system examined showed high efficacy in young adult rats. The inspection, loading and reloading of fresh product were carried out in a simple, fast and safe way; bait dispersal outside the station was only rarely observed. However, it must be taken into account that the system that require a registration by the regulatory authority must be appropriate to the species sought to be controlled. This is important due to differences in body weight between rats and mice, between males and females, and between young and aged animals, which determines the ease of entry into the station where the bait contained in its original unitary packaging is placed. (AU)

Anticoagulant rodenticides are associated with increased stress and reduced body condition of avian scavengers in the Pacific Northwest.

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.

Interest of the faecal and plasma matrix for monitoring the exposure of wildlife or domestic animals to anticoagulant rodenticides.

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.

Toxicokinetic analysis of the anticoagulant rodenticides warfarin & diphacinone in Egyptian fruit bats (Rousettus aegyptiacus) as a comparative sensitivity assessment for Bonin fruit bats (Pteropus pselaphon).

Anticoagulant rodenticides have been widely used to eliminate wild rodents, which as invasive species on remote islands can disturb ecosystems. Since rodenticides can cause wildlife poisoning, it is necessary to evaluate the sensitivity of local mammals and birds to the poisons to ensure the rodenticides are used effectively. The Bonin Islands are an archipelago located 1000 km southeast of the Japanese mainland and are famous for the unique ecosystems. Here the first-generation anticoagulant rodenticide diphacinone has been used against introduced black rats (Rattus rattus). The only land mammal native to the archipelago is the Bonin fruit bat (Pteropus pselaphon), but little is known regarding its sensitivity to rodenticides. In this study, the Egyptian fruit bats (Rousettus aegyptiacus) was used as a model animal for in vivo pharmacokinetics and pharmacodynamics analysis and in vitro enzyme kinetics using their hepatic microsomal fractions. The structure of vitamin K epoxide reductase (VKORC1), the target protein of the rodenticide in the Bonin fruit bat, was predicted from its genome and its binding affinity to rodenticides was evaluated. The Egyptian fruit bats excreted diphacinone slowly and showed similar sensitivity to rats. In contrast, they excreted warfarin, another first-generation rodenticide, faster than rats and recovered from the toxic effect faster. An in silico binding study also indicated that the VKORC1 of fruit bats is relatively tolerant to warfarin, but binds strongly to diphacinone. These results suggest that even chemicals with the same mode of action display different sensitivities in different species: fruit bat species are relatively resistant to warfarin, but vulnerable to diphacinone.

Collateral damage: Anticoagulant rodenticides pose threats to California condors.

Anticoagulant rodenticides (ARs) are widespread environmental contaminants that pose risks to scavenging birds because they routinely occur within their prey and can cause secondary poisoning. However, little is known about AR exposure in one of the rarest avian scavengers in the world, the California condor (Gymnogyps californianus). We assessed AR exposure in California condors and surrogate turkey vultures (Cathartes aura) to gauge potential hazard to a proposed future condor flock by determining how application rate and environmental factors influence exposure. Additionally, we examined whether ARs might be correlated with prolonged blood clotting time and potential mortality in condors. Only second-generation ARs (SGARs) were detected, and exposure was detected in all condor flocks. Liver AR residues were detected in 42% of the condors (27 of 65) and 93% of the turkey vultures (66 of 71). Although concentrations were generally low (<10 ng/g ww), 48% of the California condors and 64% of the turkey vultures exposed to ARs exceeded the 5% probability of exhibiting signs of toxicosis (>20 ng/g ww), and 10% and 13% exceeded the 20% probability of exhibiting signs toxicosis (>80 ng/g ww). There was evidence of prolonged blood clotting time in 16% of the free-flying condors. For condors, there was a relationship between the interaction of AR exposure index (legal use across regions where condors existed) and precipitation, and the probability of detecting ARs in liver. Exposure to ARs may complicate recovery efforts of condor populations within their current range and in the soon to be established northern California experimental population. Continued monitoring of AR exposure using plasma blood clotting assays and residue analysis would allow for an improved understanding of their hazard to condors, particularly if paired with recent movement data that could elucidate exposure sources on the landscape occupied by this endangered species.

Anticoagulant rodenticide use in oil palm plantations in Southeast Asia and hazard assessment to non-target animals.

Anticoagulant rodenticides (ARs) are used worldwide for the control of rodent pests and are the main method of control of rat pest populations in agricultural areas. The main aim of this review is to discuss the risk of ARs to non-target wildlife in oil palm areas in Southeast Asia, mainly Indonesia and Malaysia. We discussed AR use in oil palm areas and toxicities of ARs on target and non-target animals. We also reviewed published literature on wildlife species reported in oil palm areas in Southeast Asia and utilizing this information, we assessed the hazard risk of ARs to non-target wildlife in oil palm plantations. ARs are a secondary exposure hazard to rodent-consuming mammalian carnivores, such as leopard cats and civets, and rodent-consuming raptors, such as barn owls. Consumption of dead poisoned prey puts scavengers, such as water monitors, at high risk for AR exposure. Domestic livestock and granivorous birds are at high risk for AR exposure via primary exposure to toxic bait, while omnivores such as macaques and wild pigs are at moderate risk for both primary and secondary exposure to ARs. The effects of ARs on barn owls have been well studied in the field and in laboratory secondary toxicity studies. Thus, the nest-box occupancy and reproductive parameters of local barn owl populations can be monitored as an indicator of the AR exposure level in the area. CLINICAL TRIALS REGISTRATION: No clinical trials were involved in this study.

Toxicological responses to sublethal anticoagulant rodenticide exposure in free-flying hawks.

An important component of assessing the hazards of anticoagulant rodenticides to non-target wildlife is observations in exposed free-ranging individuals. The objective of this study was to determine whether environmentally realistic, sublethal first-generation anticoagulant rodenticide (FGAR) exposures via prey can result in direct or indirect adverse effects to free-flying raptors. We offered black-tailed prairie dogs (Cynomys ludovicianus) that had fed on Rozol® Prairie Dog Bait (Rozol, 0.005% active ingredient chlorophacinone, CPN) to six wild-caught red-tailed hawks (RTHA, Buteo jamaicensis), and also offered black-tailed prairie dogs that were not exposed to Rozol to another two wild-caught RTHAs for 7 days. On day 6, blood was collected to determine CPN's effects on blood clotting time. On day 7, seven of the eight RTHAs were fitted with VHF radio telemetry transmitters and the RTHAs were released the following day and were monitored for 33 days. Prothrombin time (PT) and Russell's viper venom time confirmed that the CPN-exposed RTHAs were exposed to and were adversely affected by CPN. Four of the six CPN-exposed RTHAs exhibited ptiloerection, an indication of thermoregulatory dysfunction due to CPN toxicity, but no signs of intoxication were observed in the reference hawk or the remaining two CPN-exposed RTHAs. Of note is that PT values were associated with ptiloerection duration and frequency; therefore, sublethal CPN exposure can directly or indirectly evoke adverse effects in wild birds. Although our sample sizes were small, this study is a first to relate coagulation times to adverse clinical signs in free-ranging birds.

Prevalence of anticoagulant rodenticide exposure in red-tailed hawks (Buteo jamaicensis) and utility of clotting time assays to detect coagulopathy.

Anticoagulant rodenticides (ARs) continue to be used across the United States as a method for controlling pest rodent species. As a consequence, wild birds of prey are exposed to these toxicants by eating poisoned prey items. ARs prevent the hepatic recycling of vitamin K and thereby impede the post-translational processing of coagulation factors II, VII, IX, and X that are required for procoagulant complex assembly. Through this mechanism of action, ARs cause hemorrhage and death in their target species. Various studies have documented the persistence of these contaminants in birds of prey but few have attempted to use affordable and accessible diagnostic tests to diagnose coagulopathy in free-ranging birds of prey. In our study free-ranging red-tailed hawks were found to be exposed to difethialone and brodifacoum. Eleven of sixteen (68%) livers tested for AR exposure had detectable residues. Difethialone was found in 1/16 (6%), and brodifacoum was detected in 10/16 (62%) liver samples that were tested for rodenticide residues. Difethialone was found at a concentration of 0.18 ug/g wet weight and brodifacoum concentrations ranged from 0.003-0.234 ug/g wet weight. Two out of 34 (6%) RTHA assessed for blood rodenticide had brodifacoum in serum with measured concentrations of 0.003 and 0.006 ug/g. The range of clotting times in the prothrombin time (PT) and Russell's viper venom time assays for control RTHA were 16.7 to 39.7 s and 11.5 to 91.8 s, respectively. One study bird was diagnosed with clinical AR intoxication with a brodifacoum levels in blood of 0.006 and 0.234 ug/g wet weight in blood and liver respectively, a packed cell volume (PCV) of 19%, and PT and RVVT times of >180 s. No correlation was found between PT and RVVT in the control or free-range RTHA, and there was no relationship found between the presence of liver anticoagulant residues and clotting times in the PT and RVVT.

Determining an approximate minimum toxic dosage of diphacinone in horses and corresponding serum, blood, and liver diphacinone concentrations: a pilot study.

Poisoning of nontarget species is a major concern with the use of anticoagulant rodenticides (ARs). At postmortem examination, differentiating toxicosis from incidental exposure is sometimes difficult. Clotting profiles cannot be performed on postmortem samples, and clinically significant serum, blood, and liver AR concentrations are not well-established in most species. We chose diphacinone for our study because, at the time, it was the publicly available AR most commonly detected in samples analyzed at the University of Kentucky Veterinary Diagnostic Laboratory. We determined an approximate minimum toxic dosage (MTD) of oral diphacinone in 3 horses and measured corresponding serum, blood, and liver diphacinone concentrations. Diphacinone was administered orally to healthy horses. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and serum and blood diphacinone concentrations were measured daily. At the study endpoint, the horses were euthanized, and diphacinone concentration was measured in each liver lobe. The horse that received 0.2 mg/kg diphacinone developed prolonged (>1.5× baseline) PT and aPTT; the horse that received 0.1 mg/kg did not. This suggests an approximate oral MTD in horses of 0.2 mg/kg diphacinone. Median liver diphacinone concentration at this dosage was 1,780 (range: 1,590-2,000) ppb wet weight. Marginal (model-adjusted) mean diphacinone concentrations of liver lobes were not significantly different from one another (p = NS). Diphacinone was present in similar concentrations in both serum and blood at each time after administration, indicating that both matrices are suitable for detection of diphacinone exposure in horses.

Neuropathology of feral conures with bromethalin toxicosis.

Bromethalin is a widely used neurotoxic rodenticide sometimes affecting nontarget wildlife. However, the effects of bromethalin on avian species are largely unknown. Here, we report the neuropathology of 14 feral conures (Psittacara sp.) with bromethalin toxicosis. Clinically, all birds presented with different degrees of paraparesis that sometimes progressed to dysphagia, ataxia, and tetraparesis. Histologically, there was astrogliosis, pallor, and vacuolation of white matter in the brain. This was usually more prominent in the medial longitudinal fasciculus, pons, optic tectum, cerebellar peduncle, and ventral funiculus. In most affected areas, there was loss of oligodendrocytes, and axons had extensive myelin loss or marked intramyelinic edema with splitting of myelin sheaths at the intraperiod line. Conures with bromethalin toxicosis had neuropathological changes similar to those of mammals exposed to bromethalin but with a characteristic distribution, probably related to higher susceptibility to cytotoxic edema in certain regions of the avian brain.

Short-term exposure of anticoagulant rodenticides leads to the toxin accumulation from prey (Rattus losea) to predator (Elanus caeruleus).

Rodenticides are widely used around the world since the 1950s. In Taiwan, an anti-rodent operation initiated 1977 and became a regular action annually implied by the government until 2014. This anti-rodent operation caused many animals of non-target species being exposed by rodenticides and became an environmental issue. The Black-winged Kite (Elanus caeruleus) is a small-sized diurnal raptor widely distributed in the Old World continent. Since 2000, a newly colonized population of this species occurred in Taiwan. Although the Black-winged Kites may suffer from the threats of rodenticides, the population is still growing and soon became the most abundant raptor in farmlands of Taiwan. Whether the Black-winged Kite accumulates higher anticoagulant rodenticide residues than other raptors are still unclear. In this study, liver samples of Black-winged Kites were collected from 2013 to 2016, when the detected residues of anticoagulant rodenticides increased annually. The concentration of residue rodenticide was above 0.2 ppm among 30% of the detected samples, which is the toxicity threshold concentration of other raptors. In the meanwhile, the lesser ricefield rat (Rattus losea), the most common prey of Black-winged Kites, also extended the survival period after fed on rodenticide. The longer survival days after being poisoned can enhance the predation opportunity of raptors, thus affect the accumulated rodenticides in the raptors. This study demonstrates that the Black-winged Kite has higher concentration of anticoagulant rodenticide than most other raptors, which provide the case that the raptor can quickly accumulate rodenticide residues within a short period of time.

Intoxicación por fosfuro de aluminio / Aluminum phosphide poisoning

Resumen En la industria agrícola se ha implementado el uso de plaguicidas lo que ha aumentado la cantidad y calidad de los productos agrícolas en varios países en desarrollo, su objetivo es mejorar la calidad de vida y sustento de los consumidores, sin embargo, el uso inadecuado puede causar graves intoxicaciones tanto por ingestión accidental, ocupacional o ingestión con fines suicidas u homicidas, lo cual los hace un tema de relevancia médico legal. El fosfuro de aluminio es un rodenticida, insecticida y fumigante sólido usado como una sustancia ideal para la conservación de los granos, ya que es altamente tóxico contra los insectos que invaden los granos en todos sus estadios sin afectar como tal las semillas y su germinación, es un compuesto accesible y económico lo que hace que su uso con fines suicidas y homicidas sea elevado, ante la intoxicación con fosfuro de aluminio se han descritos síntomas bastante inespecíficos como lo son dolor en el epigastrio, vómitos, diarrea, mareos, disnea y en algunos casos acompañado de un olor a ajo que es característico de ésta intoxicación lo que aumenta la sospecha clínica. Se realizó una revisión bibliográfica en diferentes bases de datos, de los artículos publicados referentes al tema de los últimos doce años, con el objetivo de profundizar en las características del fosfuro de aluminio, su mecanismo de acción y toxicidad. Se concluye que es fundamental conocer los diferentes plaguicidas y sus efectos en la salud, principalmente de aquellos con una alta letalidad, que se podrían estar utilizando clandestinamente y que al ser sumamente económicos son de fácil acceso para emplearse con fines delictivos.

Abstract The agricultural industry has implemented the use of pesticides, which has increased the quantity and quality of agricultural products in several developing countries, its objective is to improve the quality of life and livelihood of consumers, however, improper use can cause serious intoxications both by accidental ingestion, occupational or ingestion for suicidal or homicidal purposes, which makes them an issue of medico-legal relevance. Aluminum phosphide is a rodenticide, insecticide and solid fumigant used as an ideal substance for the preservation of grains, since it is highly toxic against insects that invade the grains in all their stages without affecting the seeds and their germination, it is an accessible and economic compound which makes its use for suicidal and homicidal purposes high, In the face of aluminum phosphide poisoning, quite unspecific symptoms have been described, such as pain in the epigastrium, vomiting, diarrhea, dizziness, dyspnea and in some cases accompanied by a garlic odor which is characteristic of this poisoning, which increases clinical suspicion. A bibliographic review was conducted in different databases, of the articles published on the subject in the last twelve years, with the aim of deepening in the characteristics of aluminum phosphide, its mechanism of action and toxicity. It is concluded that it is essential to know the different pesticides and their effects on health, those with a high lethality, which could be used clandestinely and which, being extremely cheap, are easily accessible to be used for criminal purposes

Acute severe pericarditis secondary to rodenticide intoxication in a dog.

Background: Pericardial effusions are well described in dogs; however, their association with rodenticide intoxication in the canine population is not widely described. Case Description: An adult mixed-breed dog was presented for 1-day history of anorexia and cough. Thoracic radiographs revealed moderate generalized cardiomegaly with globoid-shaped cardiac silhouette and mild bilateral pleural effusion. Echocardiography showed mild tamponating pericardial effusion and diffuse severe thickened pericardium. Compete blood count and blood chemistry at presentation were not specific. A coagulation profile was completed and showed severe prolongation of prothrombin time and partial thromboplastin time. Intravenous therapy with vitamin K was started at 5 mg/kg BID and on follow-up echocardiography performed 12 hours later there was evidence of complete regression of the pericardial thickening and pericardial effusion. Conclusion: To the authors' knowledge, this is the first case report describing severe pericardial thickening, constrictive pericarditis, and cardiac tamponade secondary to spontaneous anticoagulant-induced hemopericardium in dogs.