Toxicity anticoagulant rodenticides

DuVall, M.D., Murphy, M.J., Ray, A.C., Reagor, J.C. (1989). Case studies on second-generation anticoagulant rodenticide toxicities in non-target species. J. Vet. Diagn. Invest. 1(1) 66-8. 

The anticoagulant rodenticides warfarin and superwarfarins are toxic because they have high affinity for a vitamin K binding site of hepatic microsomes (Chapter 11, Section 11.2.4). In theory, an ideal biomarker would... 

TABLE 15.3. Number of exposures to long-acting anticoagulant rodenticides and deaths reported by the American Association of Poison Control Centers - Toxic Exposure... 

As a result of intensive research, derivatives of 4-hydroxycoumarin were found, which proved to be particularly efficient against rodents and resistant to anticoagulant rodenticides. Difenacoum (34) is a chronic rodenticide, which acts as a typical indirect blood anticoagulant similar to warfarin. However, it is effective against rats and mice, which are resistant to warfarin and other anticoagulant rodenticides, and is more toxic than warfarin to susceptible strains of these rodents. The chemical composition of difenacoum is 3-(3-p-biphenyl-1,2,3,4-tetrahydro-naphth-l-yI)-4-hydroxycoumarin. Its acute oral LD50 is 1.8 mg/kg for Norway rats (Hadler et al., 1975a,b). 

This group of compounds have a 4-hydroxycouma-rin ring with different side-chain substituents at the 3-position. Commonly used superwarfarin anticoagulant rodenticides in this group are bromadiolone, brodi-facoum, coumatetralyl, coumafuryl, and difenacoum. Brodifacoum, difenacoum, and bromadiolone are three of the most commonly used rodenticides around the world. Brodifacoum is the most frequently used roden-ticide in the United States. These rodenticides share most of their physical and chemical characteristics, as well as their toxicokinetics, toxicod3mamics, and mechanism of toxicity, and the medical toxicological management is the same for all superwarfarins. 

TABLE 18.3 Number of Exposures to Long-Acting Anticoagulant Rodenticides and Deaths Reported by the American Association of Poison Control Centers—Toxic Exposure Surveillance System (AAPCC-TESS) Annual Reports 24 Year Data ... 

Because rodent populations world-wide were becoming resistant to the widely used Warfarin-type anticoagulant poisons, a search was initiated to find a rodenticide with a different mode of action one that would be effective against these resistant rodents. This search led to the discovery of the toxic nature of a family of diphenyl amines which act as uncouplers of oxidative phosphorylation. A structure-activity relationship (SAR) study was undertaken to choose a derivative that would be both poisonous to rodents but still readily consumed by them. This approach led to the discovery of bromethalin,... 

Rodenticides are a broad class of chemicals designed to kill mammals, particularly rats and mice. Compounds that inhibit blood clotting, anticoagulants, are commonly used to control rat populations. One of the first was warfarin, which is related to the plant-derived coumadin (from spoiled sweet clover). In the 1950s rats developed resistance to warfarin, which prompted the development of more potent anticoagulants. Other rodenticides include fluoroacetic acid and zinc phosphide (very toxic) and thiourea-based compounds. The primary alternative to using rodenticides is trapping. 

Rodenticides are used to control rats and mice in fields, in storage areas, and in household environments. Rodents not only destroy harvested products, but are also vectors for contagious diseases. Most rodenticides belong to the coumarin group and act as anticoagulants. Bromadiolone is an example of a relative selective rodenticide that is highly toxic to rodents, but less toxic to domestic animals such as dogs and cats. 

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