title: Management of Rodent Populations by Anticoagulant Rodenticides: Toward Third-Generation Anticoagulant Rodenticides.
abstract: Second-generation anticoagulant rodenticides (SGARs) have been used since the 1980s for pest management. They are highly efficient even in warfarin-resistant rodents. Nevertheless, because of their tissue persistence, nontarget poisoning by SGARs is commonly described in wildlife. Due to this major problem, a new generation of anticoagulants must be developed to limit this risk. This study proposes a method of developing a new generation of anticoagulant rodenticides by revisiting the old SGARs based on the concept of stereochemistry. Each current SGAR is a mixture of diastereomers. Diastereomers of each compound were purified, and their biologic properties were compared by determining their ability to inhibit vitamin K epoxide reductase (VKOR) activity involved in the activation of vitamin K-dependent clotting factors and their toxicokinetic properties. Systematically, for each SGAR, both diastereomers are as effective in inhibiting VKOR activity. However, their toxicokinetic properties are very different, with one of the two diastereomers always more rapidly cleared than the other one. For all SGARs except flocoumafen, the less persistent diastereomer is always the less predominant isomer present in the current mixture. Therefore, the development of baits containing only the less persistent diastereomer would avoid the ecotoxicological risk associated with their use without decreasing their efficacy.
authors.affiliation: USC 1233 RS2GP, VetAgro Sup, INRA, University of Lyon, Marcy L'Etoile, France (M.D.P., B.E., S.L., I.F., E.B., V.L.); and Liphatech, Bonnel, Pont du Casse, France (M.D.P., H.C.).
authors.forename: Marlène
authors.initials: M
authors.lastname: Damin-Pernik
authors.affiliation: USC 1233 RS2GP, VetAgro Sup, INRA, University of Lyon, Marcy L'Etoile, France (M.D.P., B.E., S.L., I.F., E.B., V.L.); and Liphatech, Bonnel, Pont du Casse, France (M.D.P., H.C.).
authors.forename: Bernadette
authors.initials: B
authors.lastname: Espana
authors.affiliation: USC 1233 RS2GP, VetAgro Sup, INRA, University of Lyon, Marcy L'Etoile, France (M.D.P., B.E., S.L., I.F., E.B., V.L.); and Liphatech, Bonnel, Pont du Casse, France (M.D.P., H.C.).
authors.forename: Sebastien
authors.initials: S
authors.lastname: Lefebvre
authors.affiliation: USC 1233 RS2GP, VetAgro Sup, INRA, University of Lyon, Marcy L'Etoile, France (M.D.P., B.E., S.L., I.F., E.B., V.L.); and Liphatech, Bonnel, Pont du Casse, France (M.D.P., H.C.).
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fourel
authors.affiliation: USC 1233 RS2GP, VetAgro Sup, INRA, University of Lyon, Marcy L'Etoile, France (M.D.P., B.E., S.L., I.F., E.B., V.L.); and Liphatech, Bonnel, Pont du Casse, France (M.D.P., H.C.).
authors.forename: Hervé
authors.initials: H
authors.lastname: Caruel
authors.affiliation: USC 1233 RS2GP, VetAgro Sup, INRA, University of Lyon, Marcy L'Etoile, France (M.D.P., B.E., S.L., I.F., E.B., V.L.); and Liphatech, Bonnel, Pont du Casse, France (M.D.P., H.C.).
authors.forename: Etienne
authors.initials: E
authors.lastname: Benoit
authors.affiliation: USC 1233 RS2GP, VetAgro Sup, INRA, University of Lyon, Marcy L'Etoile, France (M.D.P., B.E., S.L., I.F., E.B., V.L.); and Liphatech, Bonnel, Pont du Casse, France (M.D.P., H.C.) Virginie.lattard@vetagro-sup.fr.
authors.forename: Virginie
authors.initials: V
authors.lastname: Lattard
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D015394:Molecular Structure; D010571:Pest Control / Q000379:methods*; D017207:Rats, Sprague-Dawley; D012378:Rodenticides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D064417:Vitamin K Epoxide Reductases / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D012378:Rodenticides; D064417:Vitamin K Epoxide Reductases