New Rodenticides: an Update on Recent Research Trials Gary Witmer USDA-APHIS-WS, Gary.W.Witmer@Usda.Gov

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University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Wildlife Damage Management Conferences -- Wildlife Damage Management, Internet Center for Proceedings

2013 New Rodenticides: An Update on Recent Research Trials Gary Witmer USDA-APHIS-WS, [email protected]

Katherine E. Horak USDA/APHIS/WS National Wildlife Research Center, [email protected]

Rachael S. Moulton U.S. Department of Agriculture

Roger A. Baldwin University of California - Davis, [email protected]

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Witmer, Gary; Horak, Katherine E.; Moulton, Rachael S.; and Baldwin, Roger A., "New Rodenticides: An Update on Recent Research Trials" (2013). Wildlife Damage Management Conferences -- Proceedings. 164. https://digitalcommons.unl.edu/icwdm_wdmconfproc/164

This Article is brought to you for free and open access by the Wildlife Damage Management, Internet Center for at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Wildlife Damage Management Conferences -- Proceedings by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. New Rodenticides: An Update on Recent Research Trials

Gary Witmer, Katherine Horak and Rachel Moulton USDA-APHIS-WS, National Wildlife Research Center, Fort Collins, Colorado

Roger A. Baldwin Department of Wildlife, Fish, and Conservation Biology, University of California, Davis, California

ABSTRACT: Rodents cause substantial amounts of damage and losses of foodstuffs around the world. While various methods are used to reduce damage and losses to rodents, rodenticides remain the most important tool in the toolbox. However, like all tools, rodenticides have advantages and disadvantages. Several considerations are shaping the future of rodenticide use. These include manufacturing and registration costs, concern about toxicity levels and non-target animal hazards, potential hazards to children, reduced effectiveness of some formulations, and humaneness to the targeted rodents. While there have been very few new developments in rodenticides in the last several decades, new formulations and active ingredients need to be investigated so that these concerns can be addressed. We are conducting studies on some new materials: sodium nitrite, lower concentrations of zinc phosphide, and two-active ingredient formulations (cholecalciferol plus diphacinone). Preliminary results are promising with a number of rodent species. Some materials (sodium nitrite and zinc phosphide) have been encapsulated to avoid low palatability and bait shyness issues. Preliminary cage study results are presented as well as proposed future studies.

Key Words: damage, management, pesticide regulation, risk mitigation, rodent, rodenticide

Proceedings of the 15th Wildlife Damage Management Conference. (J. B. Armstrong, G. R. Gallagher, Eds). 2013. Pp. 79-85.

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INTRODUCTION Additionally, they provide an important prey Comprising over 1,400 species world- base for many species of predatory animals. wide, rodents are the largest taxonomic Relatively few (perhaps 5%) rodent group of mammals (Nowak 1999). Rodent species around the world are serious pests. use of habitats is extensive and varied. Most Examples of genera and species of rodents rodent species are relatively small, secretive, considered to be serious pests around the prolific, adaptable, and have continuously world were provided by Prakash (1988) and growing incisors which require constant Witmer and Singleton (2010). In the United eroding by gnawing. All rodent species States (US), native species causing signifi- have ecological, scientific, social, and/or cant damage in various regions include economic values. They recycle nutrients, pocket gophers (Thomomys spp., Geomys aerate soils, distribute seeds and spores, and spp.), ground squirrels (Spermophilus spp.), affect plant succession. Some provide meat voles (Microtus spp.), deer mice and furs for people. Several species are (Peromyscus spp.), beaver (Castor canaden- used in large numbers in medical research. sis), marmots (Marmota monax), mountain beaver (Aplodontia rufa), and porcupines

(Erethizon dorsaatum). Some non-native age situations are rodent population moni- species are widespread in the US and cause toring and the establishment of thresholds damage as well: commensal rats (Rattus for acceptable levels of damage, and for spp.), house mice (Mus musculus), and nu- when to implement rodent population con- tria (Myocastor coypus; Marsh 1988). trol. Some rodent management practitioners Numerous economic and health prob- suggest less reliance on rodenticides and a lems can result from rodent interactions with more “ecologically-based” approach to ro- humans. Damage can occur to agricultural dent damage management (Singleton et al. crops (both in the field and to stored foods), 1999). Nonetheless, traps and rodenticides forests and orchards, rangelands, property remain very important tools in the IPM (structures, cables), natural resources (both toolbox for rodent damage management. faunal and floral), and disease hazards may be posed (Marsh 1988, Witmer and Single- RODENTICIDE USE AND ISSUES IN ton 2010). Singleton et al. (2003) estimated THE UNITED STATES that in Asia alone, the amount of grain eaten Rodenticides are widely used in the US by rodents would provide enough food to for the control of rodent populations in vari- feed 200 million Asians for a year. When a ous settings (e.g., agricultural lands, forests, damage situation occurs, it is very important conservation lands, urban-suburban lands; to determine the species causing the damage, Jacobs 1994). We previously presented nu- the extent of the damage, and the abiotic- merous aspects of their use in the US biotic-cultural factors involved before rodent (Witmer and Eisemann 2007). Rodenticide population and damage management strate- use in the US is regulated by the US Envi- gies are implemented (Singleton et al. 1999, ronmental Protection Agency (EPA) under Witmer and Singleton 2010). the Federal Insecticide, Fungicide and Ro- denticide Act (FIFRA; Jacobs 1994). A RODENT POPULATION AND considerable variety of rodenticides are reg- DAMAGE MANAGEMENT METHODS istered for use in the US, and these can be Worldwide, a wide variety of methods divided into several categories depending on are used to manage rodent populations di- their mode of action and toxicity (Witmer rectly or to reduce the damage caused by and Eisemann 2007). Generally, these are rodents. These methods include physical subdivided into acute rodenticides (e.g., zinc (e.g., traps, barriers), chemical (e.g., toxic phosphide, cholecalciferol, bromethalin, and baits, fumigants, repellents), biologi- fumigants), first generation anticoagulants cal/cultural (e.g., resistant plants, crop type, (e.g., chlorophacinone, diphacinone), and sanitation, habitat manipulation), and others second generation anticoagulants (e.g., (e.g., bounties, compensation; Witmer and brodifacoum, bromadiolone). The charac- Singleton 2010). Other methods are still in teristics of each of these materials were re- the developmental stages (e.g., fertility con- viewed by Timm (1994). Many of these are trol; Nash et al. 2007). Each method has available in one or more formulations: advantages and disadvantages and a site- blocks, pellets, on grains or vegetables, specific assessment should be made before powders, liquid formulations, and toxic gas- implementing a rodent damage management producing fumigants. Some chemicals used program. as rodenticides in various parts of the world Most often, an integrated pest man- are either not used in the US (e.g., com- agement (IPM) strategy is developed and pound 1080 [monosodium fluoroacetate]) or implemented that uses a variety of methods have very limited use (e.g., strychnine--- (Witmer and Singleton 2010). This is im- below ground uses only). Additionally, the- portant, in part, because a particular method se materials may be applied in various ways, of control (e.g., anticoagulant baits) may depending on the situation and regulations: become ineffective over time. Other con- in burrows, near burrow openings or along siderations in the resolution of rodent dam- runways, broadcast over broad areas by

80 hand or mechanical device, or placed in bait target animals in some situations. These stations. More recently, rodenticides are include both secondary hazards to predatory aerially broadcast from helicopters to eradi- and scavenging birds and mammals (Ebbert cate invasive rodents from islands (Witmer and Burek-Huntington 2010, Ruder et al. et al. 2007). Some rodenticides are availa- 2011, Thomas et al. 2011, Gabriel et al. ble to the general consumer for use in and 2012) as well as primary hazards to foraging around homes and other buildings and some birds (Ebbert and Burek-Huntington 2010, limited field applications, while others are Ruder et al. 2011). Most of these impacts restricted use materials available only to are attributable to anticoagulant poisoning, trained and certified pesticide applicators. but in some cases there been have non-target Rodenticides are a multi-million dollar a losses due to direct consumption of zinc year industry in the US; nonetheless, these phosphide rodenticides (e.g., Poppenga et al. materials are considered minor-use com- 2005). Finally, articles are being published pared to other pesticides such as insecticides that express concern about the humaneness and herbicides (Fagerstone 2002). It is also of methods used for rodent control (e.g., important to remember that while rodenti- Mason and Littin 2003). cides are very labor and cost effective, they The rodenticides used in the US have do not provide a permanent solution to ro- undergone a review by the EPA before re- dent problems. Where abundant food and newing registrations (Silberhorn et al. 2000). cover is available to rodents, long-term use A number of concerns about the safety of of rodenticides is required to keep popula- rodenticides have been raised, and the re- tions in check. Hence, efforts should be view resulted in many changes in what is made to reduce the area’s carrying capacity available and how these products can be for rodents. Long-term use may lead to used (Jacobs 2002). Recently, the EPA rec- some negative outcomes: rodenticide re- ommended several mitigation measures to sistance in the rodent population and residue reduce the potential hazards of a group of accumulation of certain rodenticides (e.g., nine rodenticides (brodifacoum, second generation anticoagulants) leading to bromadiolone,difethiolone, chlorophacinone, hazards to predators and scavengers. diphacinone, warfarin, bromethalin, zinc What are some of the issues surfacing phosphide and cholecalciferol) to children, regarding the use of rodenticides that make pets, and wildlife (EPA 2007). These it important for identification and testing of measures may have a variety of effects on new potential rodenticide formulations and the production and availability of rodenti- active ingredients? Some of the issues in- cides in the US (Schmit 2007, Kaukeinen clude: and Colvin 2008, Hornbaker and Baldwin Manufacturers are removing some 2010). Sizable costs are associated with the products from the commercial market registration or re-registration of a rodenti- for a variety of reasons cide product in the US, and the market and The US EPA rodenticide hazards investors can be volatile (Fagerstone et al. mitigation measures have been imple- 1990, Jacobs 1992). There is somewhat of a mented and resulted in fewer products trend towards fewer registrations and declin- available and many restrictions on uses ing use of rodenticides in the US Some current rodenticide formula- (Fagerstone et al. 1990, Jacobs 1992). tions have become much less effective Non-target losses and concerns CHARACTERISTICS OF AN “IDEAL’ have increased RODENTICIDE Humaneness concerns have in- Assuming new, effective and accepta- creased ble rodenticides need to be developed, what A number of recent papers have shown are the characteristics that should be looked that rodenticides can have impacts on non- for in new products? Researchers in Aus- tralia (O’Brien 1986, Cowled et al. 2008)

81 have discussed these ideal characteristics as death. This could potentially reduce the risk have others. We compiled a list of desirable of predators and scavengers having access to characteristics from various sources: poisoned carcasses. High toxicity We tested the efficacy of a Species specificity cholecalciferol plus diphacinone bait (C+D Palatable bait) with California voles (M. californicus). Low human hazard These voles cause much damage to arti- No resistance choke plants, and the traditional baits Fast-acting (chlorophacinone-coated bracts or zinc Painless/humane phosphide-coated bracts) were no longer very effective in reducing vole populations. Non-bio-cumulative Our cage trials found both C+D pellets and Stable in baits C+D-coated bracts were very efficacious Antidote available (70-100% mortality in the various trials) Registerable with California voles. A field efficacy trial Economical in California was completed recently, but the data (which is still being evaluated) sug- While it may be difficult to achieve all gests a lower efficacy level. The field trial these characteristics in a single rodenticide will probably be repeated because rodent product, progress can be made towards a numbers were rather low at the time of the more “ideal” rodenticide. Numerous re- first trial. searchers are investigating potential new Sodium nitrite. This new active ingre- rodenticides both in terms of active ingredi- dient is being studied as a potential new tox- ents and new formulations of existing active icant for feral pigs in Australia (Cowled et al. ingredients (e.g., Eason 1992, Eason et al. 2008, Lapidge et al. 2009) and in the US 2010). This is the basis for our research tri- (Campbell et al. 2011). Much is known als summarized below. about sodium nitrite because it is used as a meat preservative and for various industrial RECENT RODENTICIDE TRIALS uses. It can be toxic, however, if enough is Two active ingredients. There has been consumed in a short period of time. This a growing interest in incorporating two ac- results from the alteration of hemoglobin tive ingredients into rodenticide baits. There into methemoglobin which cannot transport are none currently registered in the US. oxygen. Enzymes reverse the effect over This approach would involve combining an time so that if the animal does not die, it acute toxicant with an anticoagulant. soon resumes normal activities. Some of the Connovation, Ltd., New Zealand, has been advantages of sodium nitrite are that it is experimenting with a cholecalciferol plus inexpensive, acts quickly, results in very low coumatetralyl bait and more recently with a risk of secondary hazard because it is quick- cholecalciferol plus diphacinone bait. Bell ly metabolized, and it has an antidote (meth- Labs, Wisconsin, has been experimenting ylene blue). with a cholecalciferol plus brodifacoum bait. We determined that the LD50 for 6 spe- Some of the advantages of a two active in- cies of wild-caught rodents averaged 246 gredient rodenticide are increased efficacy mg/kg which is similar to the LD50 for feral and reduced concentrations of active ingre- pigs. We also conducted preliminary food dients over those currently being used in bait and liquid bait trials. The results of single active ingredient rodenticides. It has those trials showed that rodents can eat (up also been suggested that the acute toxicant, to 60% mortality) or drink (up to 50% mor- because of its rapid “knock down” time, tality) enough sodium nitrite in a short might result in sickened animals retreating enough period of time to consume a lethal to burrows or other refugia before the anti- dose. Additional research will be needed to coagulant takes effect and causes their identify a highly palatable food bait and an

82 appropriate sodium nitrite concentration that sulated zinc phosphide-coated oats at a 0.5% results in high mortality levels in rodents. concentration than at concentrations of 1% More effective rodenticides for house and 2%. mice. Invasive house mice have been prob- We have also conducted preliminary lematic to control well or to eradicate from trials to determine if an enzyme inhibitor islands with current rodenticides in many could reduce the rate of metabolism of the situations. Our earlier trials found only 5 of anticoagulant rodenticides chlorophacinone 12 commercial rodenticide products to be and diphacinone in voles. These inhibitors effective against house mice (Witmer 2007). are found in some fruit juices which is why We investigated seven new rodenticide for- people taking blood thinners (i.e., anticoagu- mulations to identify more effective alterna- lants) are told not to consume grapefruit dur- tive rodenticides (different formulation ing treatment. Using wild-caught voles, we and/or different active ingredients). Five of found that pomegranate juice was a good the 7 new formulations of rodenticides or inhibitor of anticoagulant metabolism. The new active ingredients were found to be ef- level of enzyme inhibition was concentra- ficacious (> 70% mortality) and warrant fur- tion dependent. Additionally, it was more ther investigation as potential control meth- effective in this role than was grapefruit ods for invasive house mice. Additionally, a juice. two active ingredient rodenticide (cholecalciferol plus brodifacoum), which is CONCLUSIONS not currently registered in the US, showed We can assume that rodents will con- promise as a new house mice control tool tinue to pose challenges to land and resource (100% mortality). These may have some managers, commodity producers, and home- advantages over currently-registered inva- owners. While many tools and methods are sive house mice rodenticides. Field trials available to reduce rodent populations and with these formulations are recommended as associated damage, we need to continue to a next step in the research and pesticide reg- identify effective, safe rodenticides especial- istration process. ly for situations where existing products are Improvement of existing zinc phos- not considered effective. It is probably safe phide and anticoagulant rodenticides. Zinc to assume that much of the public will con- phosphide rodenticides are widely used tinue to be leery of toxicant use, and con- around the world. It most cases they have cerns about non-target hazards and humane- been highly effective in controlling rodent ness will increase. Hence, products need to populations. However, in some situations, not only be effective, but must also address like the California vole situation described these other concerns. Continued technology above, they are no longer considered effica- development and transfer are essential to cious. This could be for a number of rea- improve the effectiveness and safety of ro- sons (e.g., bait shyness, low palatability), denticides. We have summarized our recent but the ultimate cause is not known. To research studies which we believe are a step make it an effective rodenticide again, we in that direction. have been conducting trials to 1) determine the effectiveness of reduced concentrations LITERATURE CITED of zinc phosphide in rodenticides, and 2) CAMPBELL, T. A., D. B. LONG, and G. determine if encapsulated zinc phosphide MASSEI. 2011. Efficacy of the Boar- would be more acceptable/palatable to ro- Operated-System to deliver baits to dents. In trials with wild-caught voles, we feral swine. Preventive Veterinary found that zinc phosphide concentrations as Medicine 98:243-249. low as 0.5% were still highly efficacious COWLED, B., P. ELSWORTH, and S. LAPIDGE. (80% mortality). The concentration in exist- 2008. Additional toxins for feral pig ing commercial products is 2%. We also (Sus scrofa) control: identifying found that the voles consumed more encap-

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