RODENTICIDE EFFICACYRODENTICIDEEFFICACYWilliam W. Jacobs, Ph. D1Outline•Rodenticide ConceptsRodenticideConcepts•Development of CommensalR d ti idRodenticides•EPA’s EfficacyData Requirementsqfor Commensal Rodenticides2Commensal RodenticidesCommensalRodenticidesPesticides and pesticide productsPesticidesandpesticideproductsused to control Norway rats, roofrats and/or house micerats,and/orhousemice.3Lethal Rodenticides–The Basics•These products are created to kill rodents.•Sufficient exposure is needed to kill rodents.•For rodenticide baits, the route of exposure isvia oral ingestion.•Baits must be accepted by rodents for affi i t i d f ti t ff d tisufficientperiodoftimeto affordconsumptionof a lethal dosage.4Palatability vs. Bait ShynessPalatabilityvs.BaitShynessPalatabilityShyness•Palatability is the acceptability of the flavor ofthe bait to the rodent.•Bait Shyness is the subsequent refusal of abait initially accepted due to the perception ofillness related to the flavor of the bait. Inother contexts this effect also is known as aothercontexts,thiseffectalsoisknownasa“conditioned food aversion.”5Survivors of BaitingOperationsp•Animals that are not exposed to bait•Animals that do not find the bait to be palatable•Animals that become bait-shy•Animals that are resistant to the active ingredientThese animals become the founders of theTheseanimalsbecomethefoundersoftherebounding rodent population.6Animals Not ExposedAnimalsNotExposed•Label directions call for sustained baiting overt t l ti f i f t dstructuralportions ofinfestedarea.•Lengthening bait-exposure period, relocatingplacements and increasing amounts used perplacements,andincreasingamountsusedperplacement and area covered by placements canresult in reaching more rodents.•Immigration may not be controllable under somecircumstances (e.g., from sewers or garbage trucks).7Unpalatable BaitsUnpalatableBaits•EPA’s efficacydata requirements should limitqavailability of baits that are unpalatable ingeneral. Marginal feeders in choice trials arean indication that there may be palatabilityissues even if composite acceptance is high.U h ti f it hi t diff t•Usershave option ofswitchingto adifferentbait formulation registered for the same use.8Bait Shyness•Of the commensal rodenticides still registered in theU.S., zinc phosphide is the one most likely to havebait shyness issues.•Users can select or switch to anticoagulants or otherUserscanselectorswitchtoanticoagulantsorotheragents (e.g., bromethalin) for which true bait shynessdoes not seem to occur.•Zinc phosphide users can prebait. (Option is notavailable to “consumers” for commensal rodents)9Resistance•Behavioral (e.g., palatability or bait shyness)•Induced (low-level initial exposure stimulatesphysiological change that resists chemical)G ti ( l it i ti ti i bilit d•Genetic(exploits existing genetic variability andselects for alleles that offer protection from chemical)•Control requires chemical or other method that takesControlrequireschemicalorothermethodthattakesresistant animals.10Rodenticide History•Very early rodenticides included agents (e.g., arseniccompounds and strychnine) that people knew to bepoisonous.•These and other rodenticides including sodiumTheseandotherrodenticides,includingsodiumfluoroacetate and zinc phosphide, used prior to 1950typically were fast-acting but induced bait shyness.Initial kills were rapid, but survivors would not eat thesame bait, or often the same rodenticide again.11Rodenticide Historycont.)Rodenticide Histor( )•Prebaitingwith thegrain contained in thegtoxic bait was employed to overcome initialreluctance to feed on toxic bait and thereby toenhance knockdown.•Even with relatively short periods of baitdl t t t ddeployment, nontargetexposures occurred,often with serious consequences.12Anticoagulant Rodenticides•Serendipitous discovery of warfarin in 1940’s led tod l t f ti l t d ti id ( ddevelopmentofanticoagulants as rodenticides(andas medicines).•Warfarin other hydroxycoumarins (e g fumarin) andWarfarin,otherhydroxycoumarins(e.g.,fumarin)andindandione anticoagulants (e.g., diphacinone, pival,valone) came into common usage in the 1950’s and,as they were more effective largely replaced acuteastheyweremoreeffective,largelyreplacedacuteagents in many parts of the world.13Advantages of Anticoagulantsg•Slow mode of action and absence of “stomachpoison” quality meant essentially no bait shyness.Rodents could eat toxic amounts without detectingthat food was poisonedthatfoodwaspoisoned.•Multiple ingestions usually were needed for toxiceffects, including to nontargets.•Unlike most acute agents, anticoagulants have anantidote (Vitamin K1).14Drawbacks to Anticoagulants•Large amounts of bait are needed. Delay ofsymptoms means that rodents feed and behavesymptomsmeansthatrodentsfeedandbehavenormally for 3-4 days or longer.•Deploymentperiods of two to several weeks arey pneeded to afford feeding opportunities for residentand immigrant rodents.Careful placement and sustained monitoring is•Carefulplacementandsustainedmonitoringisneeded for efficacy and relative safety.15Resistance to AnticoagulantsResistancetoAnticoagulants•Evidence of resistance to anticoagulants first wasd t t d i S tl d i th l t 1950’ d f ddetectedinScotlandinthelate1950’s andwasfoundin all 3 major commensal rodent species by the early1970’s.•Beginning in the 1960’s, research efforts in the UK, US(1970’s), and elsewhere centered on detectingresistant populations and finding alternatives to theresistantpopulationsandfindingalternativestotheanticoagulants to which resistance had been detected.16Second-generation Anticoagulantsg•Hydroxycoumarin compounds synthesized for thepurpose of finding agents having the use advantagesof anticoagulants plus the capacity to controlpopulations resistant to the anticoagulants previouslypopulationsresistanttotheanticoagulantspreviouslyused (later called “first-generation anticoagulants”)•Initial research showed such effects for difenacoum,bromadiolone, brodifacoum.172nd-Gen. Anticoagulants(cont.)nd-Gen. Anticoagulants(cont.)()•Animals feeding on baits containing second-generationanticoagulants were more likelythan those feedingonygother anticoagulants to ingest a lethal amount over thefirst 24 hours – a plus for efficacy and a minus for safety.Sll d “ i lf di ” ff t l li d t t t•o-called“single-feeding”effectalso appliedto nontargetincidents.•Although Vitamin K1isantidotal,extendedtreatmentoug a1s a do a , e e ded ea eregimens may be needed with 2nd-generationanticoagulants.18Anticoagulant Resistance in U.S.•Not well studied: no surveillance for ~30 years, someVKORC1 mutants detected recently•Not documented for 2nd-generation anticoagulants inU S but has been elsewhere for some compoundsU.S.buthasbeenelsewhereforsomecompounds•Resistant animals would be vulnerable to bromethalin,cholecalciferol, zinc phosphide and to mechanicalmethods in addition to some or all 2nd-generationanticoagulants.19No 2nd-generation Anticoagulants inCons mer StoresConsumerStores•No effects likely if local rodents are susceptible to 1st-generationti l tancoagulants•Other control approaches available, including rodenticides thatare not anticoagulants•Selection for resistance possible only where resistanceconferring alleles are present and only if selective pressure issufficient (e.g., bait removes all susceptibles over wide area)•Consumer use of rodenticidesunlikely to be well coordinated,even within neighborhoods to exert sustained selective pressure20Efficacy Data Requirements forCommensal Rodenticides•Characterize lethalityof active ingredient to targetg gspecies: oral LD50trials with wild-type of eachspecies to be claimedD t l t bilit /l th lit f d ti id d•Documentpalatability/lethality ofrodenticide underlaboratory conditions: “choice” feeding trials with wildthe of each species to be claimed•Document ability of rodenticide to control commensalrodenticide populations: field trials with each speciesto be claimedtobeclaimed21Field Efficacy TrialsFieldEfficacyTrials•Existing infestations of target speciesExistinginfestationsoftargetspecies•Must be conducted as an experimentPretreatment and posttreatment•-treatmentandpost-treatmentactivity monitoring using at least twoindependent census methodsindependentcensusmethods22New Bait Formulations forR i t d A ti I di tRegisteredActiveIngredients•Laboratorychoice feedingtests with wild-typegNorway rats and house mice, or with certainlaboratory strains if equivalency has beenestablished (the usual case)•Penetration studies for placepacks•Rarely, field trials for odd or perishableformulations.23Palatability in Choice TestsPalatabilityinChoiceTestsPalatability•Bait and challenge diet are presented in equalamounts to test-group rodents at start of choice test.Both are novel food items.•Challenge diet is 65% whole yellow ground corn 25%Challengedietis65%wholeyellowgroundcorn,25%ground rolled oat groats, 5% corn oil, and 5% 10Xpowdered or confectioners sugar.•Bait exposure periods are 1, 2, or 15 days long,depending upon protocol selected. 3-day baitexposure periods also have been usedexposureperiodsalsohavebeenused.24Bait Form: Blocks vs. Pellets•Commensal rodenticide bait formulations registered inU S t d ffi it i ThU.S. meetor exceedefficacy criteria.The samecriteria apply for blocks and pellets if baits areregistered for typical structural uses.yp•Initial reluctance to recognize bait blocks as food hasbeen observed in some cases.•Bait blocks secured in bait stations are less likely tobe transported by rodents than are pellets or small,unsecured bait blocks.25EfficacyCriteria•Field Trials – at least 70% in reduction of pretreatment activity as determined through at least twotreatmentactivityasdeterminedthroughatleasttwoindependent census methods.•Laboratory Trials -- >90% mortality of test group with<10% mortality in control group. >33% baitacceptance (rejection <2:1 vs. challenge diet) fortrialswithbait-exposureperiods>1dayfora s t ba tposu e pe ods day oanticoagulants. Exceptions: >80% mortality and>25% acceptance for weathered baits.26Efficacy Bottom LinesEfficacyBottomLines•Active ingredients are not registered to controlgcommensal rodents unless control of allcommensal species claimed has beendemonstrated under conditions of actual use.•Bait formulations are not registered unlessth t it i f ffi i l b tthey meetcriteriafor efficacyinlaboratorychoice tests (or in field tests – an optionseldom exercised)seldomexercised).27Conclusions•Active ingredients in consumer marketActiveingredientsinconsumermarketpost-RMD have met EPA’s efficacycriteria.•Bait formulations in consumer marketpostRMD have met EPA’efficacy-RMDhavemetEPA sefficacycriteria.28