Rodenticide Resistance – An Overview

If a rodent control program fails, is it a case of rodenticide resistance? An overview of rodenticide resistance – history, incidence, mechanism and more.

As with all pesticide use, the potential for rodent populations developing resistance to rodenticides is very real. But before jumping to a conclusion that the non-performance of a rodent program is due to rodenticide resistance, it is important to exclude other potential factors for non-performance. Are the rodents actually taking the bait? Is enough bait being provided? Are additional rodents entering from outside the treatment area? If all other reasons for treatment failure can be excluded and there is repeated failure of different rodent baits on site, then rodenticide resistance may be a cause. Resistance can only be confirmed through laboratory testing and DNA analysis.

Here we take a closer look at rodenticide resistance around the world (including Australia and New Zealand).


First Generation Anticoagulant Rodenticides (FGARs)

First generation anticoagulants (warfarin, diphacinone, coumatetralyl and chlorophacinone) became widely available in rodenticide baits in the 1950s. These rodenticides impacted the vitamin K cycle resulting in excessive bleeding and death over a period of days. It is generally necessary for rodents to have multiple feeds on an FGAR bait to ingest a lethal dose. Consequently, it is not uncommon for some rodents in a population to receive a sub-lethal dose, which in turn can aid in the development of rodenticide resistance.

It was therefore not a surprise that before the end of the 1950s the first cases of resistance in the Norway Rat (Rattus norwegicus) were reported in Scotland. Over the following years, reports of resistance to warfarin and the other FGARs increased across Europe.


Second Generation Anticoagulant Rodenticides (SGARs)

The 1970s and 1980s saw the development of the Second Generation Anticoagulant Rodenticides (SGARs). The first SGARs developed were bromadiolone and difenacoum. Although they had the same mode of action as the FGARS, they were significantly more potent. However, reports of resistance to baits containing these actives started appearing in the late 1970s in Europe. However, no resistance to bromadiolone or difenacoum has been reported in Australian or New Zealand.

The more recent and more potent SGARs, brodifacoum, flocoumafen and difethialone, were introduced later as ‘resistance breakers’. To date, there have been no reported cases in the field of resistance to rodent baits containing these rodenticides in either Norway rats or house mice.


Rodent bait in bait station
SGARs were designed to be ‘resistance breakers’

Mechanism of rodenticide resistance

The mechanism of resistance to anticoagulant rodenticides is due to a mutation on the gene (Vkorc1) encoding for the vitamin K epoxide reductase (VKOR) enzyme. The VKOR enzyme is essential in activating vitamin K for its involvement in blood coagulation. Anticoagulants bind to this enzyme preventing it activating vitamin K and therefore preventing blood coagulation, which results in excessive bleeding and death. Mutations on the VKOR enzyme present in resistant rodents prevent the anticoagulants binding to the enzyme and therefore still allow the VKOR enzyme to do its job in the blood coagulation process, even in the presence of the anticoagulant rodenticide, rendering them less effective.

There are a number of different mutations of the VKOR enzyme, each of which confer different levels of resistance.


Roof rat on shelf
Rodenticide resistance is more likely to occur in areas of high rodenticide use


Resistance to non-anticoagulant rodenticides

As is the general nature of pesticide resistance, non-anticoagulant rodenticides – such as bromethalin, cholecalciferol and zinc phosphide – remain effective against anticoagulant-resistant rodents. Further, there are no reported incidences of resistance to these actives with their differing modes of action.


Measuring resistance and resistance maps

In cases of suspected rodenticide resistance (i.e. repeated failure of correctly applied baiting programs when baits have been consumed), resistance can only be confirmed through DNA testing. This is typically achieved by the pest manager taking the tip of the tail of a recently deceased rodent and sending it to a suitable laboratory. In a number of countries, especially in Europe, the process for this is well established and laboratories will perform the necessary tests.

Apart from confirming resistance or otherwise in a particular population, the collection of data allows resistance maps to be generated for individual countries. The Rodenticide Resistance Action Committee (RRAC) – which is a working group with the framework of CropLife International, and includes the leading global rodenticide companies as participants – provides rodenticide resistance maps by country. Obviously, the quality of these maps depends on the amount of data generated in each country. Europe certainly has the most rodenticide resistance maps.

Unfortunately, no such data is available in Australia and New Zealand. However, a recent study in Western Australia analysed mouse populations from Perth (where there has been significant rodenticide used over an extended period) and Browse Island (where no anticoagulant rodenticides have been used). Surprisingly, no mutation was found on the gene encoding for the VKOR enzyme in either population – which indicates no evidence of resistance in these house mouse populations.

Data on resistance in New Zealand is also somewhat limited, although a 2017 study on invasive rats across 30 sites found at least one species at each site contained gene mutations in the Vkorc1 gene.  Although only the roof rat, Rattus Rattus, contained mutations of the gene that had previously been associated with anticoagulant resistance.


Rodenticide resistance by rodent species

When it comes to rodenticide resistance, the focus is very much on the house mouse and Norway rat. These tend to be the more common rodents in the US and Europe where most of the research occurs. Data on levels of resistance in roof rat populations is very limited.

The incidence of rodenticide resistance will vary depending on location. Clearly those areas where anticoagulant rodenticides have been used over an extended period will have a higher level of incidence. Urban areas and agricultural areas would be two obvious hotspots. To actual confirm levels of resistance, actual sampling needs to occur, and this is more limited. However, a recent countrywide study in the Netherlands found resistance genes in 38% of house mouse and 15.3% of Norway rat populations.


Bait not being eaten? That’s not rodenticide resistance!

Rodents refusing to feed on baits is not evidence of rodenticide resistance. There are a number of reasons why rodents may not be taking a particular rodent bait, including:

  • Neophobia – avoiding bait boxes or the bait itself (bait shyness)
  • Too many competing food sources
  • Bait not palatable
  • Poor bait placement
  • Bait aversion – they have learnt to avoid a bait that makes them feel unwell.


Rodent management best practice

As a general rule in pest control, in areas where regular use of a pesticide is required, it is recommended to rotate between products with different modes of action. However, when it comes to rodent control, with the vast majority of products containing anticoagulants with the same mode of action, product rotation options are somewhat limited. However, following an integrated pest management approach, the use of rodent bait can be minimised, thus reducing the chances of resistance occurring. The AEPMA Code of Pest Practice for Rodent Management provides detailed information on how rodent control programs should be approached. The approach is designed to reduce rodenticide use to minimise the potential development of resistance and limit non-target and secondary poisoning events.

Whatever the rodent program put in place, when rodenticides are being used, it is good practice to whenever practically possible, ensure 100% control of the population. Allowing one or two individuals to survive after a treatment could result in a problem in the future.




Rodenticide Resistance Action Committee (RRAC).

McGee, C.F et al (2020). Anticoagulant rodenticides and resistance development in rodent pest species – A comprehensive review. Journal of Stored Product Pests, 88:

Resistance to Anti-coagulents in Western Australia?

Krijger, I.M et al (2022). Large‐scale identification of rodenticide resistance in Rattus norvegicus and Mus musculus in the Netherlands based on Vkorc1 codon 139 mutations. Pest Management Science, 70(3): 989-995. 10.1002/ps.7261

Duncan B.J.M.L., et al. (2020) Mus musculus populations in Western Australia lack VKORC1 mutations conferring resistance to first generation anticoagulant rodenticides: Implications for conservation and biosecurity. PLoS ONE 15(9):e0236234.

Cowan, P.E. et al (2017). Vkorc1 sequencing suggests anticoagulant resistance in rats in New Zealand. Pest Management Science, 73(1): 262-266.

Other useful documents:

AEPMA Code of Best Practice for Rodent Management

More information on rodents and rodent control.