Professional Pest Controller Magazine Issue 97

12 November 2019

Resistance in rodents, both behavioural and metabolic

Pest Control | PPC97 November 2019

Much has been written about the resistance to Vitamin K antagonists, more colloquially known as ‘the anticoagulants’.

Dr Mike Ayers, from BPCA member company Precision Pest Management Solutions, investigates the impact resistance is having on the control of rodents. 


  • Genetically-encoded behaviour in rodents, such as neophobia and bait shyness, boosts survival in hostile environments
  • Research suggests that rodents have behavioural resistance to bait boxes and cereal-based baits
  • Resistance is mostly a self-inflicted problem by pesticide users through poor practice
  • Studies suggest 10-20% of food sites are permanently infested creating ‘nurseries’ for further resistance
  • If a main objective is to protect wildlife then ‘undercover’ baiting could be construed as baiting indoors when dealing with internal rodent problems
  • Pricing structures should allow staff to service properties properly and conduct necessary follow-ups.

763 resistance in rodents mike ayers precision pest5

The house mouse, Mus musculus, has a natural but mild resistance to anticoagulants (Buckle AP, 2012) which, with repeated sub-lethal dosing through poor practice, results in the typical Darwinian selection of the fittest producing properly or ‘metabolically’ resistant populations of mice with the resistance genetically encoded. Unfortunately the problem doesn’t stop there.

Rats and mice have genetically encoded behavioural patterns designed to increase the survival of their species in hostile environments.

One of these behaviours in rats we know well as neophobia: the fear of new objects within their environment.

Another is aversion to food that makes them feel unwell also known as base or bait shyness (Rzoska J, 1953).

Part of this behavioural protection mechanism extends into an aversion of circumstances that result in their being eaten by predators, cats for example.

Rodents have not only evolved a nocturnal behaviour to avoid their predators, they are also very cautious in new environments.

This is why the parasite Toxoplasma gondii, when it infects rodents, induces much greater risk-taking and removes many of the behavioural cautions designed to protect the animal.

This means that the rodent then becomes much more likely to be caught by a cat, which is exactly what the parasite was after as this is its primary host (Webster JP, 2007).

As behaviour is genetically encoded then it is no surprise that, in parallel with metabolic resistance to the active ingredients, the accumulation of usage restrictions, commercial expediency and poor pest control practice has induced a growing resistance to the rodenticide delivery methods.

Rodents have not only evolved a nocturnal behaviour to avoid their predators, they are also very cautious in new environments.

Dr Mike Ayers

The primary means being the bait box over the last 50 years.

There has been some research into this, primarily by Humphries et al (1992) who identified the West Midlands Behavioural Resistant (WMBR) mice in Birmingham that exhibited avoidance behaviour to bait boxes.

Interestingly they also seemed to show an aversion to the cereal-based baits, which was possibly a part of the aversion.

This was followed up by further research (Humphries et al, 2000) that confirmed a strong aversion to cereal-based food, the main ingredient of almost all our rodenticides!

Hopefully this might have been restricted to a small area of Birmingham and while problems in London showed mouse populations with a stronger preference for meat-based baits, this may not have necessarily been an aversion to carbohydrates.

If this were to develop to a greater extent we would certainly have problems.

We expect rats to avoid traps and glue boards when newly placed in their environment, but this phobic trait of avoiding bait boxes seems now to include traps and glue boards in some house mouse populations, and appears to have spread around the country in my and many others’ experiences.

Simmons and Swindell (2017) demonstrated that reliance on bait boxes to monitor and subsequently deliver toxic bait should be treated with caution, as they demonstrated clear evidence of box and trap avoidance.

Resistance, both physiological and behavioural, is mostly a self-inflicted problem created by pesticide users through poor pest control practice.

Rodents become resistant to poor practice far quicker than to the rodenticides but eventually poor practice leads to resistance.

This has occurred for several reasons.

Pest controllers and amateurs either didn’t know what they were doing because of inadequate training or thought they could take short cuts.

The commercial pressure on pest control companies over the last 30 years has meant that follow-ups haven’t been conducted either as thoroughly or as frequently as necessary to eradicate a population.

The retail codes of practice have also contributed to the problem in that the follow-up regimes were either too lax or too onerous.

The former meant that contractors would either fail to report infestation or take the easy route for the sake of economy and simply stick to checking the boxes rather than inspecting the environment properly.

Many pest controllers seem to equate ‘no takes’ from the plastic boxes with ‘no rodents’ in the property. In my experience this is done by technicians either too rushed to spend time or too poorly trained. They miss all the other signs of infestation obvious to those not operating under those constraints of time and profit. I call this the ‘wishful thinking technique’ and it rarely works.

The retail codes of practice have also contributed to the problem in that the follow-up regimes were either too lax or too onerous.

Dr Mike Ayers

The arguably over-cautious behaviour of the legislators restricting the circumstances in which rodenticides could be used was partially responsible for the development of resistance in rat populations in the first place (Buckle AP, 2013).

Not allowing the more potent, single feed active ingredients to be used outside resulted in survival rates that generated resistance.

Similarly, I believe that in attempting to reduce the use of rodenticides, the over-cautious interpretation of new label directions and the retail market restrictions had the significant unintended consequences of exactly the opposite.

Such constraints have driven greater use of non-lethal monitoring systems, which are often inappropriately monitored.

This means that single intruder rodents entering a building have the opportunity to reproduce to greater numbers requiring even more toxic bait to kill them than might have been if used on a prophylactic basis. This is especially true in sites with high potential for re-infestation or a high risk of colonisation.

This, combined with inadequate training or supervision in the pest control industry, leads to a lack of control, reasonably high survival rates and the perfect breeding ground for developing both metabolic and behavioural resistance.

As part of their study, Simmons and Swindells (2017) identified that in a representative sample of food manufacturing sites 10 to 20% were permanently infested.

This is a very high and worrying level of infestation.

These are the genetic nurseries for developing further resistance especially in Mus musculus , although less so with rats as these tend to be permanent internal infestations much less often. However, with either species it should be a major concern for the public health authorities as well as the retail sector.

The consequence of this means that the threat to public health from rodent-borne diseases, and damage to product and reputation is now likely to increase.

Legislation from the EU isn't helping either, and it seems there is a drive to remove anticoagulants completely.

As there isn’t a viable alternative at this time, this is arguably a very dangerous direction to take.

A belief, by some in authority, that mass rodent control in complex three-dimensional cavity-based infestations can be achieved with environmental measures and rat or mouse traps alone demonstrates a significant ignorance of the nature of the problem and the adaptability of rodents.

How should the pest control industry respond to such threats?


From a point made earlier, rodents become resistant to poor practice first.

The industry certainly needs to get its act together to ensure that wildlife poisoning levels drop significantly.

The latest BPCA initiatives on improving professionalism through the BPCA Registered CPD scheme and reviewing the qualification levels necessary to be counted as a professional are to be welcomed.

Many of the problems are the result of poor training but not all.

I think that it is well accepted that the RSPH Level 2 does not necessarily make a professional.

The syllabus itself, as designed by the RSPH, has a good and reasonably comprehensive course content but was designed to be delivered over 168 hours not the four days that it has morphed into.

This has come about because of commercial pressures to get technicians trained as quickly and as cheaply as possible.

Unfortunately, the result has been inadequately equipped technicians that do not understand the consequences of their actions, in their attempts to bring infestations under control.

This is complicated by the pest control industry itself still selling perimeter bait boxes to clients, on the basis that they ‘need’ external control.

This is, and always was, a complete fallacy and really took off in 1989/90 when one company developed the green breadbin style external box as a means of achieving their profit targets rather than better pest control.

Unfortunately, every other pest control company and manufacturer jumped on the bandwagon; it is sad to see that the rate of poisoning our wildlife correlates well with the development of the external bait box.

This hasn’t changed and the development of an electronic bait box designed to prevent non-target animals might make it a little more difficult.

Experience so far is that technicians continue to report mice taking the bait from these boxes and the ‘three pass test’ to activate the gate is one that could equally be completed by a non-target animal as well as a rat.

Good business?

The problem is the contradiction in the business model.

On one side the legislators and technical managers are trying to control and limit the use of rodenticides and, on the other, the commercial managers are setting high targets for sales staff (incidentally not as well trained or experienced as technicians) who will sell as many external boxes as possible to help achieve these targets and earn bonuses.

The CRRU Stewardship scheme, while seen by many as restrictive, goes a good way towards protecting our environment by making it more likely that proper surveys are carried out, bait is used appropriately in a focused, targeted manner and removed once control has been established.

This is fine for external use as this is where non-target animals are most at risk.

Revised CRRU guidelines (July 2019) make a much clearer and welcome distinction between the use of rodenticide inside and out, acknowledging that there is a much lower risk to wildlife when bait is used inside.

The CRRU Stewardship scheme, while seen by many as restrictive, goes a good way towards protecting our environment

Dr Mike Ayers

It also acknowledges that there is no real alternative to the use of rodenticides in controlling rodent infestations and that there are sites very prone to infestation that may need prophylactic use of rodenticides on a permanent basis.

This is certainly much better for the professional pest controller, who should be capable of conducting an appropriate risk assessment to demonstrate that bait can be used safely.

However, one of the barriers to controlling box shy rodents are the constraints put upon the technician in how the bait is delivered. These are the restrictions imposed by the label.

There are two issues with the labels.

Firstly, only bromadiolone and difenacoum are approved for permanent baiting and, secondly, bait can only be used in a limited number of ways, mostly inside a tamper resistant bait box.

This presents a problem for pest controllers working to control rats in central southern England and other resistance hot spots, where both actives have been effectively declared useless but a risk assessment identifies permanent baiting to meet a threat as being necessary.

The instruction to place bait in tamper resistant bait stations is clear enough and would seem a perfectly sensible precaution, but best practice for external rat infestations is to identify the rat burrows and bait them, or use natural cover that is as secure as a tamper resistant bait station.

The allowance to use tamper resistant bait stations outside suggests these provide adequate protection to non-target animals.

The often quoted ‘tamper resistant’ bait station is certainly not the paragon of protection.

The bait inside is still very accessible to all small mammals and birds. Not only that but work by Buckle and Prescott (2010), and Quy (2011) showed that tamper-proof boxes were not well received by rats and thus delayed control, putting wildlife at greater risk by extending the baiting period.

I have always found that, when trying to control rats outside using ‘covered or protected’ bait points that aren’t bait boxes, properly secured is almost as effective as directly burrow baiting, ensures much speedier control and a shorter period of exposure to rodenticides for wildlife.

Bait used indoors is clearly ‘under cover’ from a wildlife point of view, although probably not what is meant by the label.

By its very location, assuming the building is properly proofed, there is still very little risk of access by wildlife as acknowledged by the 2019 CRRU baiting guide.

Permanent baiting of sites with a high risk of reinvasion would seem not only to be sensible but also necessary, in compliance with two key pieces of legislation often used by EHOs in the prosecution of sites with infestation: The Prevention of Damages by Pest Act 1949 and the Food Safety Act 1990.

In the latter the building or business owner has to demonstrate that all practical means of preventing the offence have been adopted.

The standard IPM techniques are relevant here but, as part of that programme, so would permanent location of toxic bait when used appropriately.

The use of non-toxic biscuit based monitoring, in my opinion, does not meet that standard as it is reactive rather than preventative, unless inspected daily.

Special delivery

The delivery methods have been found to be increasingly important, in that Murphy et al (2014) showed that the standard tamper-resistant bait box was probably the least acceptable method of delivery of bait for house mice, compared with cardboard bait boxes.

By choosing to limit its use to indoors against mice in order to protect wildlife, the next requirement would be to ensure its use in cardboard tunnels presents no risk to human health, pets and food products via CoSHH and site specific risk assessments.

It would be useful to extend this research into the control of internal rat infestations, but we probably know enough that the use of open bait trays is generally more quickly accepted by rats than plastic rat bait boxes.

The use of a plastic or metal box reduces bait take (Quy 2011), slows down the control, increases the likelihood of survival and increases the risk of resistance, as well as substantially increasing the risk to the client’s business.

This means pest controllers must find a safe way to deliver bait that complies with the label restrictions without solely relying on the plastic bait box.

When reading the Deadline Rat and Mouse Bait label it would seem that sensible bait placement in cardboard bait tunnels or open trays (when suitably covered) inside, say, a closed warehouse could be argued to comply with the letter of the directions for use as long as a proper risk assessment was carried out.

It does not define what ‘covered’ means.

Given that the ‘cover’ needs to be as good or better than a tamper resistant box performs and protects the bait from wildlife, pets, children and product, it would seem to allow some flexibility to deal with tamper box shy mice and reduce the neophobic response from rats.

This would be contingent on the pest controller being capable of conducting a sufficiently robust risk assessment to walk the line between being safe and effective at killing rodents.

This then reflects back on the quality of the training.

This means pest controllers must find a safe way to deliver bait that complies with the label restrictions without solely relying on the plastic bait box

Dr Mike Ayers

Perhaps also the regulatory authorities who dictate the contents of the label directions should take much greater direction from the end users who have practical expertise in managing rodents.

The retailer codes of practice more recently seem to have gone in the right direction; being less prescriptive, requiring the pest controller to conduct better assessments of risk of infestation and service levels required to meet that risk.

However, pest controllers should ensure that their pricing structures are adequate to allow their staff to service properties properly and conduct the necessary follow-ups, to ensure that resident populations are eliminated rather than just reduced.

Retailers and their manufacturers should therefore expect that the costs of their pest control contracts are likely to increase with the additional service demand.

Purchasing departments should not be tempted to go for the lowest possible price.

Pest control company owners and managers should encourage surveyors not to fall for the lure of a quick sale by cutting the price to win the business at any cost, because ultimately it will backfire when infestation takes hold and profitability will dwindle.

This inevitably leads to an increased risk of infestation and any money saved on the contract lost many times over because of the cost of keeping the infestation longer than necessary.

What of the future?

I think that there will be other problems with rodents adapting to our techniques and preparations as they have already.

One that might happen is that we are selecting for rodents that are much more sensitive to other components of our baits, such as denatonium benzoate, and might actively avoid bait tainted with it.

Much work is done to ensure that the bait is as palatable as possible and there is no evidence for this at present but 50 years ago we had no evidence of behavioural resistance.

The ability to taste bitter flavours is an evolutionary adaptation in most mammals to avoid eating toxic food.

Plants take advantage of this by making themselves taste bitter. Rats and mice can taste denatonium benzoate although perhaps not as well as we do.

Denatonium benzoate is used experimentally to research taste receptor physiology, the experimental animal is generally the laboratory rat.

The ability to taste bitter flavours is an evolutionary adaptation in most mammals to avoid eating toxic food.

Dr Mike Ayers

In one set of experiments (Caicedo and Roper, 2001) 17 out of 374 rats showed a response to 10µM concentration of denatonium, this is equivalent to about 5ppm.

This is half the common concentration used in rodenticides (Buckle and Kaukeinen, 1992) so it is likely that a higher proportion of rats can taste it.

At present we are culling the least sensitive rodents and selecting for the greatest aversion to the bittering agent.

If we aren’t already seeing aversion to this additive I believe we might do.

One thing is sure, if we don’t deal with our skill and training base to ensure technicians can eliminate rodent problems quickly and effectively now, we run more risks of either losing the active ingredients via legislation or the rodents out pacing our techniques.


Alejandro Caicedo A and D. Roper SD. Taste Receptor Cells That Discriminate Between Bitter Stimuli. Science. 2001 Feb 23; 291(5508): 1557–1560.

Buckle AP and Kaukleinen DE. Evaluation of aversive agents to increase the selectivity of rodenticides, with emphasis on denatonium benzoate (Bitrex TM) bittering agent. Vertebrate Pest Conference, California Volume: 15 1992.

Buckle AP and Prescott CV. Effects of tamper-resistant bait boxes on bait uptake by Norway rats (Rattus norvegicus Berk.) International Journal of Pest Management, 57 (1). pp. 77-83. 2011

Buckle AP. Anticoagulant resistance in the UK and a new guideline for the management of resistant infestations of Norway rats (Rattus norvegicus Berk.) Pest Management Science 69(3):334-341 2013.

Buckle AP. RRAG House Mouse Resistance Guideline 10 pp 2012

Humphries RE, Meehan AP and Sibly RM. The Characteristics and History of Behavioural Resistance in Inner-City House Mice (Mus domesticus) in the UK. Proceedings of 15th Vertebrate Pest Conference, University of Nebraska, 1992

Humphries RE, Sibly RM and Meehan AP. Cereal aversion in behaviourally-resistant house mice in Birmingham, UK. Appl. Anim. Behav. Sci., 66, 323-333. (erratum vol 69, 175-176) 2000.

Kerins GM, MacNicoll AD. Comparison of the half-lives and regeneration rates of blood clotting factors II, VII, and X in anticoagulant-resistant and susceptible Norway rats (Rattus norvegicus Berk.). Comp. Biochem. Physiol. C Pharmacol. Toxicol. Endocrinol. 122, 3. 1999

Murphy G, Baker RD, Thomas AF, Fowler M. The influence of bait presentation on bait uptake by mice (Mus domesticus) in infested urban domestic dwellings. January 2014 International Journal of Pest Management 60(1)

Quy R. Review of the use of bait boxes during operations to control Norway rats, Rattus norvegicus – a report to CIEH 2011

Rzoska J. Bait Shyness, A Study in Rat Behaviour British Journal of Animal Behaviour: Vol 1, Issue 4, Oct. 1953, pp. 128-135

Simmons J and Swindells C. Controlling House Mice in the Food Industry. Proceedings of the Ninth International Conference on Urban Pests 2017.

Webster JP Schizophr Bull. 2007 May; 33(3):752-6. Epub 2007

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We'll be talking more resistance at PPC Live in Harrogate next March!

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