Romano Megan C, Francis Kyle A, Janes Jennifer G, Poppenga Robert H, Filigenzi Michael S, Stefanovski Darko, Gaskill Cynthia L
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.
J Vet Diagn Invest. 2022 May;34(3):489-495. doi: 10.1177/10406387221086923. Epub 2022 Apr 2.
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.
非靶标物种中毒是使用抗凝血灭鼠剂(ARs)时的一个主要问题。在尸检时,有时很难区分中毒与偶然接触。无法对死后样本进行凝血分析,而且在大多数物种中,临床上具有显著意义的血清、血液和肝脏AR浓度尚未明确。我们选择敌鼠作为研究对象,因为当时它是肯塔基大学兽医诊断实验室分析的样本中最常检测到的市售AR。我们确定了3匹马口服敌鼠的近似最小中毒剂量(MTD),并测量了相应的血清、血液和肝脏敌鼠浓度。给健康马匹口服敌鼠。每天测量凝血酶原时间(PT)、活化部分凝血活酶时间(aPTT)以及血清和血液中的敌鼠浓度。在研究终点,对马匹实施安乐死,并测量每个肝叶中的敌鼠浓度。接受0.2mg/kg敌鼠的马出现PT和aPTT延长(>基线的1.5倍);接受0.1mg/kg的马则未出现。这表明马匹口服敌鼠的近似MTD为0.2mg/kg。此剂量下肝脏敌鼠浓度中位数为湿重1780(范围:1590 - 2000)ppb。肝叶的边缘(模型调整)平均敌鼠浓度彼此之间无显著差异(P = 无显著性差异)。给药后各时间点血清和血液中的敌鼠浓度相似,表明这两种基质都适用于检测马匹是否接触敌鼠。