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2.
Environ Pollut ; 311: 119925, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35988680

RESUMO

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.


Assuntos
Falconiformes , Rodenticidas , Animais , Anticoagulantes/toxicidade , Aves , Espécies em Perigo de Extinção , Rodenticidas/toxicidade
3.
Ecotoxicol Environ Saf ; 243: 113971, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35981482

RESUMO

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.


Assuntos
Quirópteros , Rodenticidas , Animais , Anticoagulantes/toxicidade , Quirópteros/metabolismo , Ecossistema , Mamíferos/metabolismo , Fenindiona/análogos & derivados , Ratos , Rodenticidas/toxicidade , Toxicocinética , Vitamina K Epóxido Redutases/genética , Vitamina K Epóxido Redutases/metabolismo , Varfarina/toxicidade
4.
Sci Rep ; 12(1): 12545, 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35869096

RESUMO

Anticoagulants are a major component of rodenticides used worldwide, which function by effectively blocking the vitamin K cycle in rodents. The rat Vitamin K epoxide Reductase Complex (VKORC) subunit 1 is the enzyme responsible for recycling vitamin K, and five substitution mutations (Tyr139Cys, Tyr139Ser, Tyr139Phe and Leu128Gln and Leu120Gln) located in the VKORC1 could result in resistance to anticoagulant rodenticides. This study carried out a VKORC1-based survey to estimate the anticoagulant rodenticide resistance in three Rattus species (R. losea, R. norvegicus, and R. tanezumi) collected in Hong Kong. A total of 202 rats captured in Hong Kong between 2017 and 2021 were analysed. Sequencing of molecular marker cytochrome c oxidase subunit 1 (COX1) was carried out to assist the species identification, and the identities of 52 lesser ricefield rats (R. losea), 81 common rats (R. norvegicus) and 69 house rats (R. tanezumi) were confirmed. Three VKORC1 exons were amplified from individuals by PCR followed by Sanger sequencing. A total of 47 R. tanezumi (68.1%) contained Tyr139Cys mutation in VKORC1 gene, and half of them were homozygous. None of the collected R. losea and R. norvegicus were detected with the five known substitutions leading to anticoagulant rodenticides resistance, and previously undescribed missense mutations were revealed in each species. Whole genome sequencing was further carried out on some individuals, and single nucleotide polymorphisms (SNPs) were also identified in the introns. This is the first study investigating the situation of anticoagulant rodenticide resistance in the rats collected in Hong Kong. Given that the efficacy of rodenticides is crucial for effective rodent management, regular genetic testing as well as population genomic analyses will be required to both monitor the situation and understand the adaption of different rat haplotypes for integrated pest management. Susceptibility tests for individual rodenticides should also be conducted regularly to assess their effectiveness on local species.


Assuntos
Rodenticidas , Animais , Anticoagulantes/farmacologia , Resistência a Medicamentos/genética , Hong Kong , Polimorfismo de Nucleotídeo Único , Ratos , Rodenticidas/farmacologia , Vitamina K , Vitamina K Epóxido Redutases/genética
5.
PLoS One ; 17(7): e0270568, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35857771

RESUMO

BACKGROUND: The presence of synanthropic rodents, such as Rattus norvegicus, in urban environments generates high costs of prophylaxis and control, in large part due to the environmental transmission of the pathogenic spirochete Leptospira interrogans, which causes leptospirosis. In Salvador, Brazil, The Center for Control of Zoonosis (CCZ) is responsible for planning and implementing Rodent Control Programs (RCP) which are based on chemical rodenticide. However, these strategies have not been standardized for use in developing countries. AIM: This study aimed to identify the effect of a chemical control campaign on the demographic variables of urban R. norvegicus, analyzing relative abundance, sex structure, body mass, and age of the population, as well as the characterization of spatial distribution among households, rodent capture campaigns and interventions. METHODS: This study was carried out during 2015 in three valleys of an urban poor community in Salvador. Individuals of R. norvegicus were systematically captured before (Pre-intervention) and three months (1st post-intervention) and six months (2nd post-intervention) after a chemical control intervention conducted by the CCZ in two valleys of the study area while the third valley was not included in the intervention campaign and was used as a non-intervention reference. We used analysis of variance to determine if intervention affected demographic variables and chi-square to compare proportions of infested households (Rodent infestation index-PII). RESULTS: During the chemical intervention, 939 households were visited. In the pre-intervention campaign, an effort of 310 trap nights resulted in 43 rodents captured, and in the 1st and 2nd, post-intervention campaigns resulted in 47 rodents captured over 312 trap nights and 36 rodents captured over 324 traps-nights, respectively. The rodent infestation index (PII) points did not show a reduction between the period before the intervention and the two periods after the chemical intervention (70%, 72%, and 65%, respectively). Regarding relative abundances, there was no difference between valleys and period before and two periods after chemical intervention (trap success valley 1: 0,18; 0,19; 0,18 / Valley 3 0,15; 0,17; 0,13/ P>0,05). Other demographic results showed that there was no difference in demographic characteristics of the rodent population before and after the intervention, as well as there being no influence of the application of rodenticide on the areas of concentration of capture of rodents between the campaigns. CONCLUSION: Our study indicates that the chemical control was not effective in controlling the population of R. norvegicus and provides evidence of the need for re-evaluation of rodent control practices in urban poor community settings.


Assuntos
Leptospira interrogans , Leptospirose , Doenças dos Roedores , Rodenticidas , Animais , Brasil/epidemiologia , Leptospirose/epidemiologia , Ratos , Doenças dos Roedores/epidemiologia , Roedores
6.
Sci Total Environ ; 845: 157192, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35810904

RESUMO

Control of rodent populations is a big challenge because of the rapid evolution of resistance to commonly used rodenticides and the collateral negative impacts that these products may have on biodiversity. Second-generation anticoagulants are very efficient but different single nucleotide polymorphisms (SNPs) in the Vkorc1 gene may confer resistance in rodents. We sequenced exons 1, 2 and 3 of the Vkorc1 gene from 111 mice (Mus musculus domesticus) captured across the city of Barcelona and found SNPs associated with resistance to first- and second-generation anticoagulants in all of them. Although most of the SNPs were associated with resistance to bromadiolone, we also found SNPs associated with resistance to brodifacoum. Out of all the individuals analyzed, 94.59 % carried mutations associated to introgression events with Mus spretus, a sympatric rodent species. Currently most of the chemical products for rodent control commercialized in the area are based on bromadiolone, although recent public control campaigns have already shifted to other products. Thus, the widespread occurrence of resistant mice to bromadiolone represents a challenge for rodent control in Barcelona and may increase the risk of secondary poisoning of animals preying on this species. Public health managers, pest control companies and citizens should be aware that the use of bromadiolone based products is ineffective and represents a risk for the environment, including human and animal health.


Assuntos
4-Hidroxicumarinas , Proteínas de Membrana , Rodenticidas , Vitamina K Epóxido Redutases , Animais , Anticoagulantes , Proteínas de Membrana/genética , Camundongos , Mutação , Controle de Roedores , Espanha , Vitamina K Epóxido Redutases/genética
7.
Ecotoxicology ; 31(6): 976-997, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35699849

RESUMO

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.


Assuntos
Aves Predatórias , Rodenticidas , Estrigiformes , Animais , Animais Selvagens , Anticoagulantes/toxicidade , Ásia Sudeste , Mamíferos , Ratos , Rodenticidas/toxicidade
8.
J Chromatogr A ; 1676: 463209, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35717864

RESUMO

Numerous cases of wildlife exposure to five second-generation anticoagulant rodenticides have been reported worldwide, and residues of these chiral pesticides in biological matrices are still quantified by achiral liquid chromatography methods. However, they are a mixture of cis- and trans-diastereomers, thus a mixture of four stereoisomers. Their persistence must be evaluated in a differentiated way in the food chain of concerned predator species in order to reduce the environmental impact. This article presents an evaluation of the chiral selectivity of five polysaccharide-based chiral selectors for the four stereoisomers of bromadiolone, difenacoum, brodifacoum, flocoumafen and difethialone. Different chromatographic parameters, influencing the chiral separation, such as organic modifier (acetonitrile, methanol), percentage of formic acid and water content in the mobile phase are systematically tested for all columns. It was shown that little amount of water added to the acetonitrile mobile phase may influence the retention behaviors between reversed phase and HILIC-like modes, and consequently the enantiomer elution order of the four stereoisomers. On the contrary, reversed phase is always the observed mode for the methanol water mobile phase. A suitable combination of all these parameters is presented for each second-generation anticoagulant rodenticide with a description of the enantioresolution, the enantiomer elution order and the retention times of the respective stereoisomers. A method is validated for all stereoisomers of each second-generation anticoagulant rodenticide with chicken liver and according to an official bioanalytical guideline. As an example, the enantiomer fraction is evaluated in the liver of a raptor species (rodent predator) exposed to bromadiolone and difenacoum. The results showed that only one enantiomer of trans-bromadiolone and one enantiomer of cis-difenacoum is present in hepatic residues, although all four stereoisomers are present in bromadiolone and difenacoum rodenticide baits.


Assuntos
Rodenticidas , Acetonitrilas , Anticoagulantes/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Metanol , Polissacarídeos , Rodenticidas/análise , Rodenticidas/química , Estereoisomerismo , Espectrometria de Massas em Tandem/métodos , Água
9.
Anal Bioanal Chem ; 414(19): 5829-5836, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35715587

RESUMO

Fortunately, the intentional contamination of food or water supplies out of criminal or terroristic motivation is a rather rare event. However, in the face of asymmetric warfare and as the consequences of such an event would be severe, food defence as a necessary supplement to food safety is gaining increased attention. While some progress has been made in developing non-target detection devices, the contamination of food or water supplies using readily available rodenticides may still be revealed only by complex analytical techniques. The presented study therefore aimed to develop a quick and easy screening method for the detection of sixteen globally common rodenticides in foodstuffs. Robust operation with limited personnel and analytical resources were one benchmark to be met by the method, which uses a slightly modified QuEChERS (quick, easy, cheap, effective, rugged, safe) protocol for dispersive solid-phase extraction and subsequent ion-pair chromatography with diode-array and fluorescence detection. Quantification limits were as low as 5 µg/kg with satisfying bias (recovery) and repeatability rates of 77 to 117% and 1.8 to 17.1%, respectively. The developed method provides reliable and robust detection of these deadly poisons at toxic concentrations, which was demonstrated impressively in an improvised assault scenario.


Assuntos
Rodenticidas , Alimentos , Contaminação de Alimentos/análise , Rodenticidas/análise , Extração em Fase Sólida/métodos
10.
Environ Toxicol Chem ; 41(8): 1903-1917, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35678209

RESUMO

As the dominant means for control of pest rodent populations globally, anticoagulant rodenticides (ARs), particularly the second-generation compounds (SGARs), have widely contaminated nontarget organisms. We present data on hepatic residues of ARs in 741 raptorial birds found dead or brought into rehabilitation centers in British Columbia, Canada, over a 30-year period from 1988 to 2018. Exposure varied by species, by proximity to residential areas, and over time, with at least one SGAR residue detected in 74% of individuals and multiple residues in 50% of individuals. By comparison, we detected first-generation compounds in <5% of the raptors. Highest rates of exposure were in barred owls (Strix varia), 96%, and great horned owls (Bubo virginianus), 81%, species with diverse diets, including rats (Rattus norvegicus and Rattus rattus), and inhabiting suburban and intensive agricultural habitats. Barn owls (Tyto alba), mainly a vole (Microtus) eater, had a lower incidence of exposure of 65%. Putatively, bird-eating raptors also had a relatively high incidence of exposure, with 75% of Cooper's hawks (Accipiter cooperii) and 60% of sharp-shinned hawks (Accipiter striatus) exposed. Concentrations of SGARs varied greatly, for example, in barred owls, the geometric mean ∑SGAR = 0.13, ranging from <0.005 to 1.81 µg/g wet weight (n = 208). Barred owls had significantly higher ∑SGAR concentrations than all other species, driven by significantly higher bromadiolone concentrations, which was predicted by the proportion of residential land within their home ranges. Preliminary indications that risk mitigation measures implemented in 2013 are having an influence on exposure include a decrease in mean concentrations of brodifacoum and difethialone in barred and great horned owls and an increase in bromodialone around that inflection point. Environ Toxicol Chem 2022;41:1903-1917. © 2022 Her Majesty the Queen in Right of Canada. 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.


Assuntos
Aves Predatórias , Rodenticidas , Estrigiformes , Animais , Anticoagulantes , Colúmbia Britânica , Feminino , Ratos , Rodenticidas/análise
11.
Sci Total Environ ; 838(Pt 1): 155914, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-35569667

RESUMO

Bromadiolone is an anticoagulant rodenticide (AR) commonly used as a plant protection product (PPP) against rodent pests in agricultural lands. ARs can be transferred trophically to predators/scavengers when they consume intoxicated live or dead rodents. ARs exposure in weasels Mustela nivalis, small mustelids specialized on rodent predation, is poorly known in southern Europe. Moreover, in this species there is no information on bioaccumulation of AR diastereomers e.g., cis- and trans-bromadiolone. Trans-bromadiolone is more persistent in the rodent liver and thus, is expected to have a greater probability of trophic transfer to predators. Here, we report on bromadiolone occurrence, total concentrations and diastereomers proportions (trans- and cis-bromadiolone) in weasels from Castilla y León (north-western Spain) collected in 2010-2017, where bromadiolone was irregularly applied to control outbreaks of common voles Microtus arvalis mainly with cereal grain bait distributed by the regional government. We also tested variables possibly associated with bromadiolone occurrence and concentration, such as individual features (e.g., sex), spatio-temporal variables (e.g., year), and exposure risk (e.g., vole outbreaks). Overall bromadiolone occurrence in weasels was 22% (n = 32, arithmetic mean of concentration of bromadiolone positives = 0.072 mg/kg). An individual showed signs of bromadiolone intoxication (i.e., evidence of macroscopic hemorrhages or hyperaemia and hepatic bromadiolone concentration > 0.1 mg/kg). All the exposed weasels (n = 7) showed only trans-bromadiolone diastereomer in liver, whilst a single analyzed bait from those applied in Castilla y León contained trans- and cis-bromadiolone at 65/35%. Bromadiolone occurrence and concentration in weasels varied yearly. Occurrence was higher in 2012 (100% of weasels), when bromadiolone was widely distributed, compared to 2016-2017 (2016: 20%; 2017: 8.33%) when bromadiolone was exceptionally permitted. The highest concentrations happened in 2014 and 2017, both years with vole outbreaks. Our findings indicate that specialist rodent predators could be exposed to bromadiolone in areas and periods with bromadiolone treatments against vole outbreaks.


Assuntos
4-Hidroxicumarinas , Mustelidae , Rodenticidas , Animais , Anticoagulantes , Arvicolinae , Europa (Continente) , Roedores
12.
BMJ Case Rep ; 15(5)2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35584857

RESUMO

Superwarfarin (long-acting anticoagulant rodenticide) poisoning should be suspected in unexplained bleeding with prolonged prothrombin time, especially in the absence of another explanation. Diagnosis and treatment of this intoxication remain a challenge as the direct analysis of superwarfarin in serum is not always possible. Therefore, toxin bioavailability remains unknown and close monitoring and treatment for long periods are required to avoid serious bleeding complications. Here, we discuss a case of suspected superwarfarin poisoning to highlight the challenges in early diagnosis and the challenges we encountered in treatment management and ensuring compliance for long periods.


Assuntos
4-Hidroxicumarinas , Transtornos da Coagulação Sanguínea , Intoxicação , Rodenticidas , Anticoagulantes , Transtornos da Coagulação Sanguínea/induzido quimicamente , Humanos , Intoxicação/terapia
13.
Am J Emerg Med ; 58: 349.e5-349.e7, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35527098

RESUMO

BACKGROUND: Zinc phosphide is a highly toxic rodenticide that reacts with hydrochloric acid in the stomach to form phosphine gas. Ingestion of zinc phosphide can result in consequential toxicity even when ingested in small quantities. Clear guidelines are lacking on appropriate personal protective equipment for providers to avoid additional exposure. CASE PRESENTATION: We present the case of a four-year-old boy who suffered mild gastrointestinal symptoms after an unintentional ingestion of zinc phosphide. After discussion with the regional Poison Control Center, providers wore powered air-purifying respirators in a negative pressure room and experienced no symptoms of phosphine exposure. The patient was discharged the next day after a complete recovery. CONCLUSIONS: Clinicians should be aware of the potential clinical ramifications to patients who ingest zinc phosphide and the potential risks of caring for such patients. To prevent additional exposure, providers should don appropriate personal protective equipment and contact HAZMAT (or local health department) to safely remove additional zinc phosphide.


Assuntos
Fosfinas , Rodenticidas , Criança , Pré-Escolar , Ingestão de Alimentos , Humanos , Masculino , Centros de Controle de Intoxicações , Compostos de Zinco
14.
Ecotoxicology ; 31(6): 919-932, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35622198

RESUMO

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.


Assuntos
Falcões , Rodenticidas , Animais , Anticoagulantes/toxicidade , Prevalência , Tempo de Protrombina , Rodenticidas/toxicidade
15.
J Occup Environ Hyg ; 19(7): 411-414, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35544736

RESUMO

This paper presents experimental data on the skin absorption of sodium fluoroacetate from a formulated product using an in vitro approach and human skin. Sodium fluoroacetate is a pesticide, typically applied in formulation (1080) for the control of unwanted vertebrate invasive species. It has been assigned a Skin Notation by the ACGIH, and other international workplace health regulatory bodies, due to its predicted ability to permeate intact and abraded human skin. However, there is a distinct lack of experimental data on the skin absorption of sodium fluoroacetate to support this assignment. This study found that sodium fluoroacetate, as a formulated product, permeated the human epidermis when in direct contact for greater than 10 hr. A steady-state flux (Jss) of 1.31 ± 0.043 µg/cm2/hr and a lag time of 6.1 hr was calculated from cumulative skin permeation data. This study provides important empirical evidence in support of the assignment of a Skin Notation.


Assuntos
Composição de Medicamentos , Fluoracetatos , Absorção Cutânea , Pele , Fluoracetatos/administração & dosagem , Fluoracetatos/metabolismo , Fluoracetatos/farmacocinética , Humanos , Técnicas In Vitro , Rodenticidas/administração & dosagem , Rodenticidas/metabolismo , Rodenticidas/farmacocinética , Pele/metabolismo , Fatores de Tempo
16.
Basic Clin Pharmacol Toxicol ; 131(1): 74-82, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35470573

RESUMO

OBJECTIVE: Long-acting anticoagulant rodenticide (LAAR) poisoning remains a serious public health problem. The aim of this study was to explore the clinical characteristics of different LAARs and a method of making a decision on the VK1 treatment course and the time to stop VK1 treatment safely. METHOD: This retrospective study compared the clinical characteristics of two LAARs poisoning patients and used multivariate regression method to explore the relationship between blood LAAR concentration and vitamin K1 dose/treatment time. RESULT: A total of 115 patients with LAAR poisoning were included in this study after screening. Of these, 50 patients attempted to commit suicide. The median LAAR concentration of the patients at admission was 409 (157-1174) ng/mL, and the VK1 treatment duration was 14 (8-34) days. The total VK1 treatment time in patients with LAAR poisoning was positively correlated with admission LAAR concentration. During the maintenance treatment period, the VK1 dosage was positively correlated with blood LAAR concentration. CONCLUSION: Low dose of VK1 during the maintenance period is indicative of the blood LAAR concentration being relatively low. This provides a basis for judging the LAAR content in the body during the maintenance treatment period.


Assuntos
Intoxicação , Rodenticidas , Anticoagulantes , Humanos , Intoxicação/diagnóstico , Intoxicação/tratamento farmacológico , Estudos Retrospectivos , Vitamina K 1
17.
Pest Manag Sci ; 78(6): 2704-2713, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35394111

RESUMO

BACKGROUND: Some rodent species living in arid areas show elevated physiological tolerance to anti-vitamin K rodenticides (AVKs), which seems to be due to some unknown selective pressures that rodents may experience in desert habitats. Genes involved in the ϒ-carboxylation of blood coagulation, including vitamin K epoxide reductase complex, subunit 1 (Vkorc1), ϒ-glutamyl-carboxylase (Ggcx) and NAD(P)H quinone one dehydrogenase (Nqo1) are associated with anticoagulant resistance, or some levels of elevated tolerance, in rodents. To detect whether the DNA sequences of the three genes are also under natural selection in the desert rodent species, we analyzed the Vkorc1, Ggcx and Nqo1 genes of the desert rodents and compared them with other rodent species. RESULTS: We found an accelerated evolutionary rate in Vkorc1 of desert rodents, especially in Mus spretus, Nannospalax galili and Psammomys obesus. By contrast, signals of positive selection were absent for Ggcx and Nqo1 in all species. Mapping the amino acid variations on the VKORC1 protein three-dimensional model suggested most interspecific amino acid variations occur on the outer surface of the VKORC1 pocket, whereas most intraspecific amino acid changes and known AVK resistance mutations occurred on the inner surface and endoplasmic reticulum luminal loop regions. Some desert-species-specific amino acid variations were found on the positions where known resistance mutations occurred, indicating these variations might be related to the elevated physical tolerance to AVKs in desert rodents. CONCLUSION: The evolution of Vkorc1 has been accelerated in some desert rodent species, indicating genetic preadaptation to anticoagulant rodenticides. Positive selection and relaxed selection have been detected in Psammomys obesus and Nannospalax galili, indicating the two rodent species might also show tolerance to AVKs, which needs further verification. © 2022 Society of Chemical Industry.


Assuntos
Rodenticidas , Aminoácidos , Animais , Anticoagulantes/farmacologia , Proteínas de Membrana/genética , Camundongos , Roedores/genética , Rodenticidas/farmacologia , Vitamina K Epóxido Redutases/genética , Vitamina K Epóxido Redutases/metabolismo
18.
Pestic Biochem Physiol ; 183: 105052, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35430058

RESUMO

Rodent control is mainly done using anticoagulant rodenticides leading to the death of rodents through internal bleeding by targeting the VKORC1 protein. However, mutations in VKORC1 can lead to resistance to anticoagulant rodenticides that can cause treatment failure in the field. This study provides the first insight into the distribution, frequency and characterization of Vkorc1 mutations in roof rats (Rattus rattus) in France and in three administrative areas of Spain. The roof rat is present in France while it was thought to have almost disappeared with the expansion of the brown rat. Nevertheless, it has been found mainly in maritime areas. 151 roof rats out of 219 tested presented at least one missense mutation in the coding sequences of Vkorc1 gene (i.e. 69.0% of the rat). Nine Vkorc1 genotypes were detected (Y25F, A26P, R40G, S57F, W59C, W59R, H68N, Y25F/K152T and Y25F/W59R. Biochemical characterization of the consequences of these different genotypes proved that these various genotypes did not induce severe resistance to anticoagulant rodenticides. Even if many mutations of the Vkorc1 gene are present in roof rat populations in France, their management may be based in a first approach, considering the low levels of resistance induced, on the use of first-generation anticoagulants less dangerous for wildlife. The use of second-generation may be considered when treatment failure is observed or when bait consumption is limited.


Assuntos
Rodenticidas , Animais , Anticoagulantes/farmacologia , Resistência a Medicamentos/genética , França , Mutação , Mutação de Sentido Incorreto , Ratos , Rodenticidas/farmacologia , Espanha , Vitamina K Epóxido Redutases/genética
19.
J Vet Diagn Invest ; 34(3): 489-495, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35369800

RESUMO

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.


Assuntos
Fenindiona , Rodenticidas , Animais , Anticoagulantes , Cavalos , Fígado , Fenindiona/análogos & derivados , Fenindiona/toxicidade , Projetos Piloto , Rodenticidas/toxicidade , Soro
20.
Environ Sci Pollut Res Int ; 29(40): 60908-60921, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35435551

RESUMO

Wildlife exposures to pest controlling substances have resulted in population declines of many predatory species during the past decades. Many pesticides were subsequently classified as persistent, bioaccumulative, and toxic (PBT) and banned on national or global scales. However, despite their risks for non-target vertebrate wildlife, PBT substances such as anticoagulant rodenticides (ARs) are still permitted for use in Europe and have shown to threaten raptors. Whereas risks of ARs are known, much less information is available on emerging agrochemicals such as currently used PPPs and medicinal products (MPs) in higher trophic level species. We expect that currently used PPPs are relatively mobile (vs. lipophilic) as a consequence of the PBT criteria and thus more likely to be present in aqueous matrices. We therefore analyzed blood of 204 raptor nestlings of three terrestrial (red kite, common buzzard, Montagu's harrier) and two aquatic species (white-tailed sea eagle, osprey) from Germany. In total, we detected ARs in 22.6% of the red kites and 8.6% of the buzzards, whereas no Montagu's harriers or aquatic species were exposed prior to sampling. ΣAR concentration tended to be higher in North Rhine-Westphalia (vs. North-Eastern Germany) where population density is higher and intense livestock farming more frequent. Among the 90 targeted and currently used PPPs, we detected six substances from which bromoxynil (14.2%) was most frequent. Especially Montagu's harrier (31%) and red kites (22.6%) were exposed and concentrations were higher in North Rhine-Westphalia as well. Among seven MPs, we detected ciprofloxacin (3.4%), which indicates that risk mitigation measures may be needed as resistance genes were already detected in wildlife from Germany. Taken together, our study demonstrates that raptors are exposed to various chemicals during an early life stage depending on their sampling location and underpins that red kites are at particular risk for multiple pesticide exposures in Germany.


Assuntos
Falconiformes , Aves Predatórias , Rodenticidas , Animais , Animais Selvagens , Anticoagulantes , Monitoramento Ambiental/métodos , Alemanha , Rodenticidas/análise
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