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Determining an approximate minimum toxic dosage of diphacinone in horses and corresponding serum, blood, and liver diphacinone concentrations: a pilot study.
Abstract: 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 ( = 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.
Publication Date: 2022-04-02 PubMed ID: 35369800PubMed Central: PMC9254070DOI: 10.1177/10406387221086923Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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The researchers carried out a study to find the minimum toxic dosage (MTD) of diphacinone, an anticoagulant rodenticide, in horses and measured its concentration in serum, blood, and liver. They concluded that horses that received a dosage of 0.2mg/kg of diphacinone developed prolonged clotting times and suggested this as the MTD for horses. The study also found similar diphacinone concentrations in blood and serum at each time point after administration.
Study Design
- The researchers conducted a study on three horses to determine the minimum toxic dosage (MTD) of diphacinone, an anticoagulant rodenticide commonly found in samples analyzed at the University of Kentucky Veterinary Diagnostic Laboratory.
- The team administered oral doses of diphacinone to the horses to track the effects.
- They performed daily measurements of prothrombin time (a measure of blood clotting performance) and activated partial thromboplastin time (another blood clotting factor). They also measured serum and blood diphacinone concentrations.
- At the end of the study, the horses were euthanized, and diphacinone concentration was measured in each liver lobe.
Findings
- Based on the observations, the horse that received a dosage of 0.2 mg/kg diphacinone experienced an extended prothrombin time and activated partial thromboplastin time, indicating a delay in blood clotting. This was absent in the horse that received a lower dosage (0.1 mg/kg), so the researchers suggested an MTD of 0.2mg/kg for horses.
- The median liver diphacinone concentration at this dosage was found to be 1,780 ppb wet weight.
- There were no significant differences in the concentrations of diphacinone across different liver lobes.
- Diphacinone was present in similar concentrations in both serum and blood at each time after administration. This suggests both blood and serum as suitable matrices for detecting diphacinone exposure in horses.
Significance
- The findings of this study are significant in providing a reference dosage of diphacinone that could cause toxicity in horses. This could guide veterinarians and animal health professionals in assessing potential poisoning in horses and taking necessary precautionary measures.
- The finding that diphacinone concentrations were similar in serum and blood indicates that either could be used in testing for rodenticide exposure, simplifying the process and providing alternatives based on practical consideration in a clinical setting.
Cite This Article
APA
Romano MC, Francis KA, Janes JG, Poppenga RH, Filigenzi MS, Stefanovski D, Gaskill CL.
(2022).
Determining an approximate minimum toxic dosage of diphacinone in horses and corresponding serum, blood, and liver diphacinone concentrations: a pilot study.
J Vet Diagn Invest, 34(3), 489-495.
https://doi.org/10.1177/10406387221086923 Publication
Researcher Affiliations
- Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
- California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
- University of Pennsylvania School of Veterinary Medicine, New Bolton Center, Kennett Square, PA, USA.
- Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
MeSH Terms
- Animals
- Anticoagulants
- Horses
- Liver
- Phenindione / analogs & derivatives
- Phenindione / toxicity
- Pilot Projects
- Rodenticides / toxicity
- Serum
Conflict of Interest Statement
The authors declared no potential conflicts of interest with respect to the
research, authorship, and/or publication of this article.
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