title: Assessment of ruminal degradation, oral bioavailability, and toxic effects of anticoagulant rodenticides in sheep.
abstract: OBJECTIVE
  To assess the rate and extent of ruminal degradation of warfarin, chlorophacinone, and bromadiolone in vitro and determine the oral availability and clinical and hemostatic effects of each anticoagulant rodenticide in adult sheep.
  
  
  METHODS
  3 Texel sheep.
  
  
  METHODS
  Samples of ruminal fluid were incubated with each of the anticoagulants to assess the kinetics of ruminal degradation over 24 hours. To determine the plasma kinetics of the anticoagulants, each sheep received each of the anticoagulants IV or via a rumenimplanted cannula at 2-month intervals (3 rodenticide exposures/sheep). At intervals during a 240- to 360- hour period after treatment, prothrombin time (PT) was measured, plasma anticoagulant concentration was assessed, and clinical signs of rodenticide poisoning were monitored. In plasma and rumen extracts, anticoagulant concentrations were determined via high-performance liquid chromatography.
  
  
  RESULTS
  In the rumen extracts, anticoagulants were slightly degraded (< 15%) over 24 hours. In vivo, oral availability of warfarin, chlorophacinone, and bromadiolone was estimated at 79%, 92%, and 88%, respectively. Although maximum PT was 80 seconds after chlorophacinone and bromadiolone treatments, no clinical signs of toxicosis were detected; PT returned to baseline values within 2 weeks.
  
  
  CONCLUSIONS
  In sheep, warfarin, chlorophacinone, and bromadiolone were not degraded in the rumen but their bioavailabilities were high after oral administration; the kinetics of these compounds in sheep and other mammals are quite similar. These data suggest that the lack of susceptibility of ruminants to these anticoagulant rodenticides cannot be explained by either ruminal degradation or the specific toxicokinetics of these anticoagulants.
authors.affiliation: Unité Mixte de Recherché Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Lyon Metabolisme et Toxicologie Comparés des Xénobiotiques, Ecole Nationale Vétérinaire de Lyon, BP 83, F-69280 Marcy l'étoile, France.
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Berny
authors.forename: Laurent Alves
authors.initials: LA
authors.lastname: de Oliveira
authors.forename: Bernadette
authors.initials: B
authors.lastname: Videmann
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Rossi
mesh_terms: D015110:4-Hydroxycoumarins / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D000925:Anticoagulants / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D001682:Biological Availability; D007189:Indans / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D012378:Rodenticides / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D012417:Rumen / Q000378:metabolism*; D012756:Sheep / Q000378:metabolism*; D012757:Sheep Diseases / Q000139:chemically induced*; D014859:Warfarin / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D015110:4-Hydroxycoumarins; D000925:Anticoagulants; D007189:Indans; D012378:Rodenticides; C004662:chlorophacinone; D014859:Warfarin; C021636:bromadiolone