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 ( 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.