Resistance anticoagulant rodenticides

Brodifaeoum has been marketed in several countries for the eontrol of a wide range of rodent pest species. It is available as a 0.005% pellet for rat and mouse control, a smaller 0.001% pellet for field rodent eontrol, and as 29 g wax bloeks for sewer rat eontrol. It is the only anticoagulant rodenticide found to produee 100% mortality in most rodent speeies after only a 24 h dose (Chalermehaikit et al, 1993). Brodifaeoum was effeetive against warfarin-resistant rats and miee in 1984, but the possibility of resistance has been raised (Lund, 1984). 

Lund, M. (1984). Resistance to the second-generation anticoagulant rodenticides. Proceedings of the 11th Vertebral Pesticide Conference, Sacramento, CA, p. 89. 

The concentration of bromethalin in rodent baits is 0.005% or 0.01%. It is effective against rodents that are resistant to anticoagulant rodenticides and does not induce bait shyness. Anorexia and neurological effects occur after an effective dose has been consumed. 

It is also very effective against rodents resistant to anticoagulant rodenticides (Gratz, 1973). Its action is relatively slow, but the animal dies without pain 6-8... 

The wide application of anticoagulant rodenticides for more than 20 years has gradually increased the genetic resistance of rodents to these active substances. Warfarin resistance and cross-resistance to similar anticoagulants predominate in certain territories to such an extent that it impedes the practical use of these active substances (Gratz, 1973). 

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). 

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). 

Sources. Bromethalin, which is available to the public, was developed in the 1980s as an alternative rodentid to use against warfarin-resistant rats and mice however, it is generally used less frequently than anticoagulant rodenticides or cholecalciferoi. 

The widespread resistance, recently encountered in rats, to the anticoagulant rodenticide warfarin (6.55), seems to be of this type. Ribosomes from resistant animals contain less warfarin than normal, due to replacement of the usual binding protein by one with less affinity (Martin, 1973). 

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. 

The rodenticidal efficacy of warfarin increases with admixture of calciferol in many anticoagulant-resistant rodent species. The mixture is semi-acute in action. 

An even more important derivative is 3-[3-(4 -bromobiphenyl-4-yl)-1,2,3,4-tetrahydronaphth-l-yl]-4-hydroxycoumarin (brodifacoum, 35). This anticoagulant of exceptional potency is capable of control resistant rodents as well as several noncommensal species. Contrary to first generation anticoagulants, a bait concentration of only SO mg/kg brodifacoum is adequate to give control even in a single feeding for most species. As with other anticoagulants, vitamin K, is an effective antidote. In contrast with other acute rodenticides, symptoms are delayed and no bait shyness is observed (Dubock and Kaukeinen, 1978). Its effectiveness... 

Due to their potent anticoagulant activity, some of these compounds have been used to control rodent infestation. Particularly, warfarin has been applied as an effective rodenticide for years. The laevorotatory form of this compound is seven times more active than the dextrorotatory isomer [471]. Recently, a resistance to warfarin has been found to develop in some rats [483]. These animals may metabolise the drug more rapidly or the affinity of the receptor sites for vitamin K may be greater in the resistant animals than in the sensitive ones, hence the coumarin is metabolised and eliminated faster. 

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