Resistance to anticoagulant rodenticides.

Abstract

This chapter defines anticoagulant rodenticide resistance and reviews its history and genetics in Norway rat (Rattus norvegicus), house mouse (Mus musculus) and other rodent species. The mechanisms of resistance (vitamin K cycle, biochemical resistance), the distribution and occurrence of resistance, and the practical effects of resistance and cross-resistance are described. The detection tests for and management of anticoagulant resistance are discussed.

Anticoagulant Rodenticide Toxicity to Non-target Wildlife Under Controlled Exposure Conditions

“…Studies with warfarin in chicken, ostrich (Stuthio camelus), mallard, crow (Corvus macrorhynchos) and snowy owl (Bubo scandiacus) describe inter-specific differences in warfarin metabolism that could account for inter-specific differences in sensitivity (Watanabe et al 2010(Watanabe et al , 2015. As previously suggested (Rattner et al 2014a), it might be possible that AR tolerance in some non-target species may be related to differences in the primary structure of VKOR that has been reported in genetically resistant rodents (Pelz et al 2005). Preliminary investigation of the primary structure of VKORC1L1 in 14 species of birds using GenBank suggests that the primary structure of VKORC1L1 is highly conserved in the region of the active site (N. Karouna-Renier, personal communication).…”

“…This observation is not uniform among ARs (USEPA 1998), and some studies suggest that male rats and mice seem to be more sensitive to difenacoum than females (Winn et al 1987). While not the objective of this chapter, a major research effort entailing controlled exposure studies has characterized the development, magnitude and genetic basis of resistance to first-and second-generation ARs in "target" Norway rats and other rodents (e.g., Greaves and Cullen-Aryes 1988;Thijssen 1995;Pelz et al 2005;Prescott et al 2007;Buckle 2013). The issue of differential sensitivity between sexes extends into the realm of genetically-based AR resistance (Pelz et al 2005;Berny 2011), with resistantfemale rodents often exhibiting greater tolerance than resistant-males (e.g., Wallace and MacSwiney 1976;Thijssen 1995).…”

“…It is believed that ARs bind tightly to the proposed warfarin-binding site of VKOR at tyrosine residue 135 in close proximity to the active site (cysteines 132 and 135) of this 163 amino acid enzyme (Tie and Stafford 2008). Notably, some point mutations can impede AR binding and thus confer resistance in target pest species (Boyle 1960;Pelz et al 2005).…”

Anticoagulant Rodenticides and Wildlife: Introduction

“…Despite the prevailing opinion that warfarin was both safe and effective, evidence began to accrue that some rodent populations were developing resistance to some FGARs (e.g., warfarin and diphacinone, Boyle 1960;Cuthbert 1963;Lund 1964). Possible mechanisms of resistance development include mutations at the receptor site with decreased binding affinity of the compounds (Lasseur et al 2006;Meerburg et al 2014;Pelz and Prescott 2015) or by modulation of metabolic activity (Ishizuka et al 2008;Markussen et al 2007).…”

Brodifacoum Toxicity in American Kestrels (Falco sparverius) with Evidence of Increased Hazard on Subsequent Anticoagulant Rodenticide Exposure

“…It is not clear if liver AR residues are uniformly diagnostic of a potentially toxic dose evoking anticoagulant effects; such a cause–effect relationship may not be appropriate (US Environmental Protection Agency ). Furthermore, there are genetic and biochemical variants of VKOR that afford resistance (VKORC1, VKORC1L1; Pelz et al ; Hammed et al ), as well as other pharmacokinetic (e.g., cytochrome P450–mediated, AR binding; Watanabe et al , ) and possibly diet‐based (Thijssen ) mechanisms that could result in AR tolerance.…”