Superwarfarin rodenticides

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... 

Superwarfarins Second-generation anticoagulant rodenticides related to warfarin. 

Superwarfarin rodenticides are used to kill urban and agricultural rodent pests. They are readily available to the general public and pest controllers, are easy to obtain and conceal, so may pose a risk of being used as chemical warfare agents (EPA, 2003, 2005 WHO, 2003, 2008). 

This group of compounds have a 4-hydroxycoumarin ring with different side-chain substituents at the 3-position. Commonly used superwarfarin anticoagulant rodentieides in this group are bromadiolone, brodifacoum, coumate-tralyl, coumafuryl, and difenacoum. Brodifacoum, difena-coum and bromadiolone are three of the most commonly used rodentieides around the world. Brodifacoum is the most frequently used rodenticide in the USA. These rodentieides share most of their physical and chemical characteristics, as well as their toxicokinetics, toxicody-namics, and mechanism of toxicity, and the medical toxicological management is the same for all superwarfarins. 

Identification of superwarfarins is easy today. Analytical methods for the detection of these products in serum and tissues are readily available. Routine laboratory tests for coagulopathy may help support the need for such analytical chemistry testing. Stockpiles of vitamin Ki may be useful to consider, particularly in places where large stocks of superwarfarin rodenticides are used such as hvestock areas. 

Community education programs should be developed to inform residents about superwarfarin rodenticides and other household commercial chemicals with the potential to be used as chemical warfare or terror agents. Fact sheets may be one method of informing the pubhc. Identifying those at risk and when they should be informed may be a useful part of this education campaign - this may also improve security in industrial plants, and limit any access from outsiders in all industrial and storage facilities where flammable or highly toxic chemicals are stored, particularly livestock facilities. 

Robben, J.H., Kuijpers, E.A., Mout, H.C. (1998). Plasma superwarfarin levels and vitamin K1 treatment in dogs with anticoagulant rodenticide poisoning. Vet. Q. 20(1) 24-7. 

Brodifacoum is a member of the second-generation anticoagulant rodenticides known as superwarfarins (27). This compound and others like it (e.g., bromadiolone and difenacoum) were developed to combat rodent resistance to warfarin (27). 

Five superwarfarin rodenticides (chlorophacinone, bromadiolone, difetfaialone and cis- and tmn.rextracted from serum and separated on Cg column (2 = 285 nm or 265 nm, ex 400 nm, em). Very good peak shapes were generated with a 45/25 acetonitrile/water (20 mM acetate buffer at pH 4.7 with 1 mM tetrabutylammonium hydroxide) mobile phase [978]. Detection limits for UV were 20-75 ng/mL, whereas for fluorescence Aey were 3-l2ng/mL (however, chlorophacinone and difethialone did not fluoresce). Concentration curves were linear from 100 to 1000 ng/mL. 

Kuijpers EAP, den Hartigh J, Savelkoul TJF, e Wolff FA. A method for the simultaneous identification of five superwarfarin rodenticides in human serum. J Anal Toxicol 1995 19(7) 557-62. 

Lipton, R.A., Klass, E.M., 1984. Human ingestion of a "superwarfarin" rodenticide resulting in a prolonged anticoagulant effect. JAMA 252 (21), 3004-3005. 

Watts, R.G., Castleberry, R.P., Sadowski, J.A., 1990. Accidental poisoning with a superwarfarin compound (brodifacoum) in a child. Pediatrics 86, 883-887. Weitzel, J.N., Sadowski, J.A., Furie, B.C, et al, 1990. Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum clinical and metabolic studies of three cases. Blood 76 (12), 2555-2559. 

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