Study on risk mitigation measures for anticoagulant rodenticides as biocidal products : Final report

Rodent pest control worldwide relies largely on the use of anti-vitamin K anticoagulant rodenticides (ARs). ARs have considerably changed our practice and perspectives for rodent control. The delayed action of these compounds, with mortality occurring several days after bait consumption, makes them particularly effective against neophobic species such as the Norway rat (Rattus norvegicus). The intensive use of these compounds has been rapidly followed by the selection of resistant strains in Norway rats, roof rats (Rattus rattus) and house mice (Mus musculus and M. domesticus). ARs are usually classified as First Generation AR (FGAR) (warfarin, chlorophacinone, coumatetralyl), requiring several days of feeding to be fully active, Second Generation ARs (SGARs) (bromadiolone, difenacoum, brodifacoum, flocoumafen, difethialone), more potent and active after only one day of feeding. Bromadiolone and difenacoum are considered less potent than the other SGARs and resistance to them is described, while there is no evidence of ‘practical’ resistance on the field to the three other SGARs. Alternatives to ARs are limited today. Alphachloralose has been registered as a biocidal product against mice only. Cholecalciferol has been recently submitted as an active substance to the EU. Because of its delayed action, it can overcome neophobia, although bait aversion has been demonstrated against Norway rats. Old compounds (zinc phosphide, sodium selenite, bromethalin) all may have some interest but also have major drawbacks (either in terms of efficacy, toxicity to non-target species or lack of antidotes). Methaemoglobin-forming compounds are currently being investigated as rodenticides but usually act too fast to be good rodenticides. ARs are also being reconsidered with modern tools in order to separate their activity and their persistence. With the exception of the above, there is no evidence that chemical alternatives to ARs will be available in the next 5 years, (no results anticipated before 2020). Because chemical control of rodents relies almost exclusively on ARs, many distinct resistant strains of Norway rats and house mice have been identified. These resistant strains have developed specific genetic traits through a modification of the VKOR enzyme involved in the catalytic recycling of vitamin K and through enhanced metabolism of the active ingredient by means of the induction and over expression of selected CYP450 isoforms. The most widely spread resistance mechanism appears to be related to VKOR alterations and specifically Single Nucleotide Polymorphisms of the VKORC gene (resulting from a single mutation in the DNA sequence), at least in rats and mice. A lot of work still needs to be conducted on these mutations to determine precisely the level of resistance conferred by each Single Nucleotid Polymorphism (SNP). Resistant strains have been identified in most western European countries, but information is lacking for most central, eastern and southern parts of Europe. Other countries in the world also have detected mutated strains. Resistance testing can be done either via in vivo tests (BCR for instance) or by in vitro identification of the mutations. Because of its simplicity and lower cost, the latter appears to be the most promising tool, provided field information is available on the level of resistance associated with each mutation. This technique could be used to monitor AR resistance in all EU countries, with information presented using GIS mapping by dedicated institutions