[Rodent Control] Warfarin: A Forgotten Weapon

August 10, 2004

Rodenticide baits form the cornerstone of many or most rodent pest management programs. Modern baits and formulations offer an economical, generally safe method of knocking down rat and mouse infestations as part of an integrated pest management strategy.

However, the Environmental Protection Agency (EPA) recently has raised concerns about the safety of the most widely used rodenticides, the so-called "second-generation" anticoagulants, and may soon impose new use restrictions aimed at reducing non-target exposure. This comes at a time when the pest professional needs more tools, not less. It may be time to consider adding warfarin baits to the PCO toolbox again. Warfarin has some benefits, as well as some real and perceived shortcomings.

HISTORICAL PERSPECTIVE. Warfarin revolutionized the rodent control business when it first appeared on the market in 1950. It was different from the highly toxic rat and mouse poisons used at that time (i.e., strychnine and zinc phosphide). I asked Rex Marsh, professor emeritus at the University of California-Davis, about the early impacts of warfarin: "Rat control levels of 90 percent or better soon became the norm with warfarin — compared with the 70 to 80 percent, at best, that PCOs could achieve with pre-baited acute poison baits available at that time — with the exception of 1080," he said. (Note: Compound 1080 rodenticide uses were canceled by the EPA in 1988.)

Such rodenticides killed quickly after a single feeding, but control was often poor if rodents failed to eat a lethal dose at the first meal. Rodents could become bait-shy. Bait shyness occurs when a fast-acting poison makes an animal sick before it has eaten a lethal dose. Further control with any kind of bait becomes more difficult. In addition, with no antidote to most of the acute rodenticides, the risk to unintended targets could only be managed with careful placements.

This all changed with the introduction of warfarin, a slow-acting blood thinner (or anticoagulant). Although rodents had to feed on warfarin baits several times over several days, the slow action also prevented bait-shyness from developing. Rodents didn’t associate the gradually developing sickness with the bait, and would return to feed several times over several days. In addition to improved performance, there is a readily available antidote for warfarin — vitamin K.

Warfarin was so safe and effective to use compared to earlier rodenticides that it came to be used almost constantly in some places. Consequently, as early as 1958, the pest control industry and scientists in Great Britain noted that warfarin seemed to be losing effectiveness at some sites. Researchers determined that some rats and mice were genetically resistant to the compound. With constant warfarin use, susceptible rodents were being killed and the resistant individuals appeared to dominate local populations. Beginning about 1971, similar reports of apparent resistance emerged from North Carolina, New York and California. To make matters worse, warfarin-resistant rodents appeared to be resistant to some of the other anticoagulants that had been developed, such as chloro-phacinone and diphacinone. This phenomenon was labeled "cross-resistance."

In response to the discovery of warfarin-resistant rodents, the pest control industry fell back upon the acute, single-feeding rodenticides. At the same time, rodenticide manufacturers pushed to developed new, more potent anticoagulants. The effort was successful, with compounds like brodifacoum, bromadiolone and most recently difethialone appearing on the U.S. market in the last 25 years. These "second-generation" anticoagulants are strong enough to be considered acute toxicants, since a single feeding can kill a rat or mouse. The mode of action is the same as warfarin, and vitamin K is antidotal. While some cases of "cross-resistance" have been reported, the second generation of anticoagulants have been effective replacements for warfarin for several decades now.

REGULATORY CONCERNS. However, a regulatory backlash has been building as reports of non-target incidents attributed to the second-generation products have accumulated over the years. In 1998, the EPA issued the first of a series of documents that may lead to new limits on the use of second-generation anticoagulants. The Re-registration Eligibility Documents (REDs) for a cluster of rodenticides were issued that year. The REDs describe data gaps in the toxicology profile of each rodenticide. Individual companies must generate the missing research data in order to keep their product registrations active and on the market.

The draft version of an EPA "comparative assessment of rodenticide risks" was issued in 2002. The final version is to be issued this summer. In this case, rodenticide manufacturers have joined together and formed a task force to respond to the agency. The task force reviewed EPA’s methods and interpretations of the scientific data. A carefully crafted industry response was very critical of the draft document. (This response has been made available for public viewing as an EPA Docket Document and can downloaded at www.pctonline.com/industryresponse). In spite of this, indications are that the final document will not be very different from the draft version.

While no one can predict the agency’s future actions, the outcome of the process may be greater restrictions on the uses of many popular rat and mouse baits. In Dec. 2002, EPA issued a report titled "Potential Risks of Nine Rodenticides to Birds and Nontarget Mammals: A Comparative Approach." Included in this document is a graph summarizing potential hazards posed to non-target birds and mammals by the rodenticides. (This graph can be downloaded at www.pctonline.com/epagraph.)

Warfarin is ranked among the safest rodenticides by the EPA. This can be attributed to two characteristics of the compound. First, the slow action provides a large window for medical intervention in cases of accidental child or pet poisoning. Second, warfarin is rapidly metabolized and excreted from the body. The half-life, or the time required for the warfarin load in the body to decrease by one half, is about 42 hours. Warfarin is also used in humans, under the trade name Coumadin, for blood clot and stroke prevention. Most people who undergo surgeries such as coronary by-pass or joint replacements, take Coumadin for clot prevention. By contrast, the second-generation anticoagulants are not readily metabolized.

Warfarin is not as potent as many other rodenticides. It is typically formulated at 250 parts per million, about five times higher than other anticoagulants. The low potency and slow action required that baits be supplied in relatively large quantities with closely spaced placements, and that fresh bait be offered for a longer time than is sometimes needed with other rodenticides.

The length of exposure may not be as important as originally thought with warfarin. In lab tests, 50 percent of Norway rats died after a single day’s exposure to warfarin baits. Historical data from our studies of both first- and second-generation anticoagulants reveal that mortality curves, or time until death after ingestion of bait, is surprisingly similar among all the anticoagulant compounds. Maintaining a constant supply is the most critical factor to success with warfarin baits.

OTHER CONSIDERATIONS. Mice are generally harder to control with warfarin than rats. They are erratic feeders, and the availability of even small quantities of alternative foods will dilute the dietary concentration of the rodenticide. However, recent studies in our laboratory have demonstrated that 100 percent mortality in mice can be achieved after five days of exposure.

Poor acceptance was a problem often associated with warfarin baits in the past. But now it has been well established that the problem lies with impurities found in poor quality warfarin. Highly purified warfarin mixed with fresh, high-quality ingredients is well accepted by rodents. The Wisconsin-based bait manufacturer HACCO (www.hacco.com) imports a nearly pure form of warfarin that excels in baits.

Professor Marsh says that he believes that part of warfarin’s reputation for poor palatability stems from the fact that warfarin was initially marketed as a dilute concentrate. Buyers prepared their own baits. Often an inappropriate grain was selected, or poor quality grain was used, and the predictable result was poor acceptance.

Probably the greatest concern surrounding warfarin is resistance. How important is this in most situations? The answer is that it will rarely be an issue. However, in the case that a pest management professional encounters this problem, he or she must be aware of the situation and monitor it carefully. Genetic resistance to warfarin among rats is not widespread. Wild house mice we have trapped from various locales where resistance had been reported in the 1970s, failed to survive the World Health Organization (WHO) screening test with warfarin. In addition, the very definition of warfarin resistance has been called into question in recent years.

Both the New York State Health Department, and Genesis Laboratories in Colorado, have tested the effects of warfarin on Norway rats from Chicago that are "warfarin resistant" as defined by the WHO. According to WHO standards, rats that can survive six days of feeding on a 50 part-per-million (ppm) warfarin bait are "resistant." Yet, we found that when rats that passed this test were fed the normal, commercial strength 250 ppm warfarin bait, 85 percent mortality was achieved in a simulated field test. In this test the rats were offered a choice between the warfarin bait and conventional rodent chow.

Tests by the N.Y. State Health Department showed that repeated exposures to 50 ppm warfarin baits (alternated with 30 day "clean-out" periods) will kill almost all "resistant" Norway rats. Researchers Stephen Frantz and Constance Madigan concluded that, "… resistant Norway rats are likely to die upon re-exposure to warfarin, the very product which is used to identify or define their resistance."

Warfarin baits are still very effective for routine rat control. Adrian Meehan, in the classic reference Rats and Mice: Their biology and control (1984), states that "It is generally recognized that long-term feeding of warfarin to susceptible (brown) rats will invariably produce complete mortality." (p. 160). According to Robert M. Corrigan, Ph.D., "…small daily exposures [to warfarin] over a short period give a high percentage of kill (90-100%)", (Rodent Control: A Practical Guide For the Pest Management Professional [2001]).

So, does warfarin belong in the rodent control arsenal of the pest professional? Any rodenticide should be just one part of a well-considered IPM program. A good IPM program will include educating the client, reducing and removing conditions that attract pests, and minimizing the use of pesticides. When pesticides are necessary, select the least toxic, safest pesticide that will get the job done. In many cases warfarin can fill the bill. In other cases, alternative products will do the job. Just as with controlling insects, pest management professionals must use all of the available tools in their toolbox.

Professor Marsh notes that "Warfarin has the greatest non-target safety margin of all currently used anticoagulant baits, [and] efficacy is only marginally sacrificed for safety. Warfarin may be preferred where safety to non-targets is a greater concern than resistance."

The author is a senior scientist with Genesis Laboratories Inc., Wellington, Colo. He can be reached at jbaroch@giemedia.com.