Pharmacokinetics of Anticoagulant Rodenticides in Target and Non-target Organisms

Horak, Katherine E.; Fisher, Penny; Hopkins, Brian

doi:10.1007/978-3-319-64377-9_4

Cited by 43 publications

(30 citation statements)

References 78 publications

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“…Given the relatively short half-lives of ARs in blood (Horak et al 2018) and their generally rapid decline in concentration in other studied species, in the cited field studies it seems reasonable to assume that the positive serum detections reflect recent exposure. In the present study, it is potentially less straightforward to interpret the temporal significance of the serum AR detections in birds diagnosed with AR toxicosis given that the only birds positive in serum were those lethally affected by ARs and that blood was collected postmortem in all but 3 birds (Table 3).…”

Section: Temporal Interpretation Of Serum Ar Levelsmentioning

confidence: 99%

Continued Anticoagulant Rodenticide Exposure of Red‐tailed Hawks (Buteo jamaicensis) in the Northeastern United States with an Evaluation of Serum for Biomonitoring

Murray

2020

Enviro Toxic and Chemistry

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Prior studies (2006-2016) in birds of prey admitted to a wildlife clinic in Massachusetts, USA, revealed widespread exposure to second-generation anticoagulant rodenticides (SGARs) among red-tailed hawks (Buteo jamaicensis, RTHAs). Continued monitoring of species for which historic data are available can reveal trends in exposure that aid in evaluating the effectiveness of risk-mitigation measures. While the majority of exposure-monitoring studies utilize liver tissue collected postmortem, antemortem modalities, such as serum analysis, may be desirable for risk assessments in certain populations. However, the sensitivity of serum for detecting anticoagulant rodenticides (ARs) is not well studied. Paired liver and serum samples from 43 RTHAs were evaluated from 2017 to 2019. In liver tissue, 100% of birds were positive for ARs, with the SGARs brodifacoum, bromadiolone, and difethialone identified most frequently; 91% of birds had liver residues of 2 to 4 ARs. These findings represent the highest exposure both to ARs overall and to multiple ARs in RTHAs compared to previous studies. All birds diagnosed with AR toxicosis (n = 14) were positive for ARs in serum; however, all subclinically exposed birds (n = 29) were negative in serum. These data show that exposure to SGARs remains widespread in RTHAs in this geographic area. In addition, although serum analysis is not sensitive for detecting sublethal exposures in RTHAs, it can potentially support a diagnosis of AR toxicosis in conjunction with other consistent signs.

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Section: Temporal Interpretation Of Serum Ar Levelsmentioning

confidence: 99%

Continued Anticoagulant Rodenticide Exposure of Red‐tailed Hawks (Buteo jamaicensis) in the Northeastern United States with an Evaluation of Serum for Biomonitoring

Murray

2020

Enviro Toxic and Chemistry

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“…Furthermore, hepatic residues of brodifacoum remain elevated in kestrels for a sustained period (months) (Rattner et al unpubl. ), as has been demonstrated in many species of mammals (reviewed in Horak et al 2018). The apparent absence of an effect of the chlorophacinone challenge dose in kestrels was in contrast to that elicited by a warfarin challenge dose in brodifacoum treated rats (Mosterd and Thijssen 1991), and may be due to species difference in AR pharmacokinetics or VKOR activity and its inhibition.…”

Section: Discussionmentioning

confidence: 69%

Is Sensitivity to Anticoagulant Rodenticides Affected by Repeated Exposure in Hawks?

Rattner¹,

Lazarus²,

Bean³

et al. 2018

vertebrate_pest_conference

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A seminal question in wildlife toxicology is whether exposure to an environmental contaminant, in particular a secondgeneration anticoagulant rodenticide, can evoke subtle long lasting effects on body condition, physiological function and survival. Many reports indicate that non-target predators often carry residues of several rodenticides, which is indicative of multiple exposures. An often-cited study in laboratory rats demonstrated that exposure to the second-generation anticoagulant rodenticide brodifacoum prolongs blood clotting time for a few days, but weeks later when rats were re-exposed to the first-generation anticoagulant rodenticide warfarin, coagulopathy was more pronounced in brodifacoum-treated rats than naïve rats exposed to warfarin. To further investigate this phenomenon, American kestrels were fed environmentally realistic doses of chlorophacinone or brodifacoum for a week, and following a week-long recovery period, birds were then challenged with a low-level dietary dose of chlorophacinone. In the present study, neither hematocrit nor clotting time (prothrombin time, Russell's viper venom time) were differentially affected in sequentially exposed kestrels compared to naïve birds fed low-level dietary dose of chlorophacinone. While the present findings do not reveal lasting effects of anticoagulant exposure on blood clotting ability, findings in laboratory rats and other species have demonstrated such effects on blood clotting, and even other molecular pathways associated with immune function and xenobiotic metabolism. Additional studies using an environmentally realistic route of exposure and dose are underway to further test this hypothesis.

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“…These data demonstrate brodifacoum persistence in the liver of birds. Various studies in laboratory rodents indicate that the half‐life of brodifacoum in liver may be as long as 350 d (reviewed in Horak et al ), and a year‐long sampling study in birds (Japanese quail gavaged at 0.4 mg brodifacoum/kg body wt) predicted the half‐life to be 297 d using a single‐phase decay model (Butler ). Using this same single‐phase model, estimated brodifacoum half‐life in liver and kidney of American kestrels (cumulative 7‐d brodifacoum dose ~0.76 mg/kg body wt) over a 4‐wk period was only 27.7 and 34.6 d, respectively.…”

Section: Discussionmentioning

confidence: 99%

Brodifacoum Toxicity in American Kestrels (Falco sparverius) with Evidence of Increased Hazard on Subsequent Anticoagulant Rodenticide Exposure

Rattner

Volker

Lankton

et al. 2020

Enviro Toxic and Chemistry

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A seminal question in ecotoxicology is the extent to which contaminant exposure evokes prolonged effects on physiological function and fitness. A series of studies were undertaken with American kestrels ingesting environmentally realistic concentrations of the second-generation anticoagulant rodenticide (SGAR) brodifacoum. Kestrels fed brodifacoum at 0.3, 1.0, or 3.0 µg/g diet wet weight for 7 d exhibited dose-dependent hemorrhage, histopathological lesions, and coagulopathy (prolonged prothrombin and Russell's viper venom times). Following termination of a 7-d exposure to 0.5 µg brodifacoum/g diet, prolonged blood clotting time returned to baseline values within 1 wk, but brodifacoum residues in liver and kidney persisted during the 28-d recovery period (terminal half-life estimates >50 d). To examine the hazard of sequential anticoagulant rodenticide (AR) exposure, kestrels were exposed to either the first-generation AR chlorophacinone (1.5 µg/g diet) or the SGAR brodifacoum (0.5 µg/g diet) for 7 d and, following a recovery period, challenged with a low dose of chlorophacinone (0.75 µg/g diet) for 7 d. In brodifacoum-exposed kestrels, the challenge exposure clearly prolonged prothrombin time compared to naive controls and kestrels previously exposed to chlorophacinone. These data provide evidence that the SGAR brodifacoum may have prolonged effects that increase the toxicity of subsequent AR exposure. Because free-ranging predatory and scavenging wildlife are often repeatedly exposed to ARs, such protracted toxicological effects need to be considered in hazard and risk assessments. Environ Toxicol Chem 2020;39:468-481. © 2019 SETAC

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Pharmacokinetics of Anticoagulant Rodenticides in Target and Non-target Organisms

Cited by 43 publications

References 78 publications

Continued Anticoagulant Rodenticide Exposure of Red‐tailed Hawks (Buteo jamaicensis) in the Northeastern United States with an Evaluation of Serum for Biomonitoring

Continued Anticoagulant Rodenticide Exposure of Red‐tailed Hawks (Buteo jamaicensis) in the Northeastern United States with an Evaluation of Serum for Biomonitoring

Is Sensitivity to Anticoagulant Rodenticides Affected by Repeated Exposure in Hawks?

Brodifacoum Toxicity in American Kestrels (Falco sparverius) with Evidence of Increased Hazard on Subsequent Anticoagulant Rodenticide Exposure

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