Bromadiolone Concentrations Research Articles

Weasel exposure to the anticoagulant rodenticide bromadiolone in agrarian landscapes of southwestern Europe.

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.

Anticoagulant Rodenticide Contamination of Terrestrial Birds of Prey from Western Canada: Patterns and Trends, 1988-2018.

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.

Temporal Persistence of Bromadiolone in Decomposing Bodies of Common Kestrel (Falco tinnunculus).

Bromadiolone is a second generation anticoagulant rodenticide (SGAR) used to control pest rodents worldwide. SGARs are frequently involved in secondary poisoning in rodent predators due to their persistence and toxicity. This study aims to evaluate the persistence of bromadiolone in liver at different stages of carcass decomposition in experimentally-dosed common kestrels (Falco tinnunculus) to understand the possibility of detecting bromadiolone in cases of wildlife poisoning and the potential risk of tertiary poisoning. Twelve individuals were divided into the bromadiolone-dose group (dosed with 55 mg/kg b.w) and the control group. Hepatic bromadiolone concentrations found in each stage of decomposition were: 3000, 2891, 4804, 4245, 8848, and 756 ng/g dry weight at 1–2 h (fresh carcass), 24 h (moderate decomposition), 72 h, 96 h (advanced decomposition), seven days (very advanced decomposition), and 15 days (initial skeletal reduction) after death, respectively. Liver bromadiolone concentrations in carcasses remained relatively stable over the first four days and raised on day 7 of decomposition under the specific conditions of this experiment, presenting a risk of causing tertiary poisoning. However, at the initial skeletal reduction stage, liver bromadiolone concentration declined, which should be considered to interpret toxicological analyses and for proper diagnosis. This experimental study provides for the first time some light to better understand the degradation of SGARs in carcasses in the wild.

Study on the pharmacokinetics of bromadiolone in oral poisoning rabbits

Objective: To investigate the variations of bromadiolone concentration in blood and its metabolism in rabbits after oral administration of bromadiolone, and to provide reference for the study of bromadiolone metabolism. Methods: Designed absolute alcohol (1 g/kg) reagent control group, high dose (0.3 mg/kg) and low dose group (0.05 mg/kg) , there were 6 rabbits in each group. Blood samples were collected from the rabbit central auricular artery at regular intervals as 1 h, 2 h, 4 h, 8 h, 12 h, 16 h, 24 h, 36 h, 48 h, 72 h, 168 h, 336 h, 504 h after oral administration. The samples were centrifuged within 1 h. Prothrombin time (PT) , activated partial thromboplastin time (APTT) and concentrations of bromadiolone in plasma were tested. Metabolic kinetics data was analyzed by DAS 3.0.2 software. Results: Bromadiolone had no significant effect on the body weight of the experimental rabbits during the experimental period (P>0.05) . PT and APTT were significantly abnormal in different dose groups, but for occurrence of exception, PT was earlier than APTT. The concentration of bromadiolone in plasma reached the peak value 12 h after gavage in both high-dose and low-dose groups. The absorption time of t(1/2Ka) in high-dose group was 4.34 h, the clearance time of t(1/2) was 81.52 h, the absorption time of t(1/2Ka) in low-dose group was 6.90 h, and the elimination time of t(1/2) was 56.38 h. The atrioventricular model of bromadidone was three compartment model in rabbits. Conclusion: Bromadiolone can be absorbed rapidly by oral administration, but its metabolism is slow. The change of bromadiolone in vivo accords with the three compartment model.

Exposure of non-target small mammals to anticoagulant rodenticide during chemical rodent control operations.

The extensive use of anticoagulant rodenticides (ARs) results in widespread unintentional exposure of non-target rodents and secondary poisoning of predators despite regulatory measures to manage and reduce exposure risk. To elucidate on the potential vectoring of ARs into surrounding habitats by non-target small mammals, we determined bromadiolone prevalence and concentrations in rodents and shrews near bait boxes during an experimental application of the poison for 2weeks. Overall, bromadiolone was detected in 12.6% of all small rodents and insectivores. Less than 20m from bait boxes, 48.6% of small mammals had detectable levels of bromadiolone. The prevalence of poisoned small mammals decreased with distance to bait boxes, but bromadiolone concentration in the rodenticide positive individuals did not. Poisoned small mammals were trapped up to 89m from bait boxes. Bromadiolone concentrations in yellow-necked mice (Apodemus flavicollis) were higher than concentrations in bank vole (Myodes glareolus), field vole (Microtus agrestis), harvest mouse (Micromys minutus), and common shrew (Sorex araneus). Our field trials documents that chemical rodent control results in widespread exposure of non-target small mammals and that AR poisoned small mammals disperse away from bating sites to become available to predators and scavengers in large areas of the landscape. The results suggest that the unintentional secondary exposure of predators and scavengers is an unavoidable consequence of chemical rodent control outside buildings and infrastructures.

Depletion of bromadiolone in tissues of hogs following oral exposure

Objectives: To assess bromadiolone depletion in the edible tissues of swine and propose post-exposure withdrawal periods. Materials and methods: Two groups of barrows and two groups of gilts were given a single oral dose of bromadiolone: low dosage (LD, 0.05 mg/kg; n = 20; 10 males, 10 females) and high dose (HD, 0.5 mg/kg; n = 20; 10 males, 10 females). Coagulation parameters were assessed before and after administration. Animals were sacrificed at 1, 2, 3, 5, and 6 weeks (LD) and 1, 2, 3, 6, and 9 weeks (HD) post dosing. Loin muscle, skin-adherent fat, liver, feces, and blood were analyzed for bromadiolone using liquid chromatography-tandem mass spectrometry. Results: Partial thromboplastin times exceeded control values in the LD and HD groups 6 and 9 weeks post dosing, respectively. In the HD group, bromadiolone concentrations exceeded the limit of detection (LOD) at all time points in liver and skin-adherent fat and for up to 6 weeks in feces, muscle, and plasma. In the LD group, bromadiolone concentrations exceeded the LOD at all time points in liver and up to 3 weeks in fat, feces, and plasma. Estimated withdrawal periods for bromadiolone in liver were 83 and 176 weeks in the LD and HD groups, respectively, and 62 weeks in muscle in the HD group. Implication: Bromadiolone residues persist in tissues such that it is impractical to wait for the hog to eliminate the rodenticide to a concentration that is safe for entry into the human food chain.

Kinetics of bromadiolone in rodent populations and implications for predators after field control of the water vole, Arvicola terrestris

We document the kinetics of bromadiolone in two rodent populations after a field control of water voles, and their implications for predator exposure. Water voles and common voles were trapped aboveground and underground from 1 to 135 days after bromadiolone treatment in the field. Livers, digestive tracts, and rests of the body were analyzed separately. Our results indicate that 99.6% of the water voles trapped underground and 41% of the common voles trapped aboveground contain bromadiolone residues. Concentrations were maximal between 3.3 and 6.5 days after treatment, according to the tissues examined and the model applied for water voles, and after 1.3 to 3.7 days for common voles. Water voles appeared available almost exclusively for foraging predators. Common voles, found less likely to be poisoned and exhibiting weaker concentrations, were mainly sampled aboveground. The liver, primarily eaten by some predators and scavengers, contains a larger bromadiolone quantity (59% of the total amount found in water voles). The rejection of the digestive tract by those species may lead to a subsequent consumption of voles with higher bromadiolone concentrations (from + 3.8 to + 5.8% of concentration) and provide a moderate risk increase. After 135 days, eight of the ten water voles and one of the two common voles exhibited detectable residues. Additionally, one specimen presented higher concentrations than the others, and similar to those measured in Voles trapped between the first 15–20 days. This may have consequences on predator intoxications several months after treatment. These results integrate individual differences for the two main rodent species present in treated areas. Implications for predator exposure were investigated at the end of the study and suggest that, if the risk of secondary poisoning is maximal during the first 15–20 days when the rodent densities remain high, exposure conditions are maintained for at least 135 days.

Bromadiolone Poisoning: LC–MS Method and Pharmacokinetic Data

Poisoning with superwarfarins, like bromadiolone, is a growing public health problem, and the mortality is high. Pharmacokinetic data on bromadiolone in humans are however scarce, and there are no reports following repeated exposures to bromadiolone. We have developed a method for quantification of bromadiolone in whole blood, using liquid chromatography-mass spectrometry (LC-MS). The analytical method is reported. Limit of detection was 0.005 mg/L and limit of quantification was 0.01 mg/L. The concentrations of bromadiolone in whole blood and plasma in serial samples from a 62-year-old woman were measured. The half-life of bromadiolone in blood was estimated to be about 6 days in the initial phase of elimination and about 10-13 days in the terminal phase. The mean plasma/blood ratio of bromadiolone was 1.7 +/- 0.6. Stability testing of bromadiolone in whole blood samples after two cycles of freeze and thaw revealed that bromadiolone concentrations decreased.

How environment and vole behaviour may impact rodenticide bromadiolone persistence in wheat baits after field controls of Arvicola terrestris?

We aimed to evaluate whether environmental factors affect the persistence of bromadiolone in baits in field treatment. Baits were distributed in three soils according to two types of distribution: (1) artificial galleries conform to agricultural practices; (2) storage cavities to mimic bait storage by voles. Persistence was evaluated for 30 days in galleries and 80 days in storage cavities in autumn and spring. The decrease of bromadiolone concentrations was described by a first-order kinetic model. In galleries, the half-lives ranged from 3.0 to 5.1 days in autumn and from 5.4 to 6.2 days in spring. The half-lives were similar between soils and seasons but the pattern of persistence differed lightly for two soils between seasons. Half-lives in storage cavities, 42.7 and 24.6 days in autumn and spring respectively, were longer than in galleries. To conclude, both soil characteristics and climatic conditions weakly influence persistence, while bait storage lengthens it dramatically.