RODENTICIDE EFFICA

RODENTICIDE EFFICA

William W. Jacobs, Ph. D
Outline

• Rodenticide Concepts Rodenticide Concepts• Development of Commensal 

R d ti id Rodenticides

• EPA’s Efficacy q Data Requireme

for Commensal Rodenticides
Commensal Rodenticid

Commensal Rodenticid

Pesticides and pesticide produPesticides and pesticide produ

used to control Norway rats, ro

rats and/or house mice rats, and/or house mice.
Lethal Rodenticides 

– The Bas

• These products are created to kill roden• Sufficient exposure is needed to kill rode• For rodenticide baits, the route of expos

via oral ingestion.

• Baits must be accepted by rodents for a 

suffi i t i d f ti t ff d 

ffi

cien

t perio

d o

f time 

to affor

d consum

of a lethal dosage.
Palatability vs. Bait Shyne

Palatability Palatability vs. Bait Shyne

Shyne

• Palatability is the acceptability of the fla

the bait to the rodent.

• Bait Shyness is the subsequent refusa

bait initially accepted due to the percepillness related to the flavor of the bait. other contexts this effect also is known other contexts, this effect also is known 

“conditioned food aversion.”
Survivors of Baitin

g p O

perati

• Animals that are not exposed to bait• Animals that do not find the bait to be palatabl• Animals that become bait-shy•

Animals that are resistant to the active ingredie

These animals become the founders of the These animals become the founders of the

rebounding rodent population.
Animals Not Exposed Animals Not Exposed

• Label directions call for sustained baiting over 

st t l ti f i f t d truc

tural portions o

f in

fes

t

e

d area.

• Lengthening bait-exposure period, relocating 

placements and increasing amounts used per placements, and increasing amounts used per

placement and area covered by placements caresult in reaching more rodents.

• Immigration may not be controllable under som

circumstances (e.g., from sewers or garbage tr
Unpalatable Baits Unpalatable Baits

• EPA’s efficac

y q data re

quirements shoul

availability of baits that are unpalatable general. Marginal feeders in choice triaan indication that there may be palatabiissues even if composite acceptance is 

• U h ti f it hi t diff 

Users 

have option o

f swit

ching 

to a diffe

bait formulation registered for the same 
Bait Shyness

• Of the commensal rodenticides still registered 

U.S., zinc phosphide is the one most likely to hbait shyness issues.

• Users can select or switch to anticoagulants or 

Users can select or switch to anticoagulants or 

agents (e.g., bromethalin) for which true bait shdoes not seem to occur.

• Zinc phosphide users can prebait. (Option is n

available to “consumers” for commensal roden
Resistance

• Behavioral (e.g., palatability or bait shyness)• Induced (low-level initial exposure stimulates 

physiological change that resists chemical)

• G ti ( l it i ti ti i bilit 

Genetic (exploits existing genetic variability an

selects for alleles that offer protection from che

• Control requires chemical or other method tha

Control requires chemical or other method tha

resistant animals.
Rodenticide Histor

y

• Very early rodenticides included agents (e.g., a

compounds and strychnine) that people knew tpoisonous.

• These and other rodenticides including sodium These and other rodenticides, including sodium

fluoroacetate and zinc phosphide, used prior to typically were fast-acting but induced bait shyn

Initial kills were rapid, but survivors would not esame bait, or often the same rodenticide again
Rodenticide Histor Rodenticide Histor

y( ) cont.

)

• Prebaitin

g g with the 

grain contained in th

toxic bait was employed to overcome inreluctance to feed on toxic bait and therenhance knockdown.

• Even with relatively short periods of bait 

dl t t t deploymen

t, non

targe

t exposures occur

often with serious consequences.
Anticoagulant Rodenticide

• Serendipitous discovery of warfarin in 1940’s le

d l t f ti l t d ti id development of anticoagulants as rodenticides 

as medicines).

• Warfarin other hydroxycoumarins (e g fumari

Warfarin, other hydroxycoumarins (e.g., fumari

indandione anticoagulants (e.g., diphacinone, pvalone) came into common usage in the 1950’s 

as they were more effective largely replaced aas they were more effective, largely replaced a

agents in many parts of the world.
Advantag g es of Anticoagula

• Slow mode of action and absence of “stomachpoison” quality meant essentially no bait shyne

Rodents could eat toxic amounts without detecthat food was poisoned that food was poisoned.

• Multiple ingestions usually were needed for tox

effects, including to nontargets.

• Unlike most acute agents, anticoagulants have 

antidote (Vitamin K1).
Drawbacks to Anticoa

gulan

• Large amounts of bait are needed. Delay of 

symptoms means that rodents feed and behavsymptoms means that rodents feed and behav

normally for 3-4 days or longer.

• De

py p lo

yment 

periods of two to several weeks a

needed to afford feeding opportunities for residand immigrant rodents.

• Careful placement and sustained monitoring is Careful placement and sustained monitoring is

needed for efficacy and relative safety. 
Resistance to Anticoagula

Resistance to Anticoagula

• Evidence of resistance to anticoagulants first wa

d t t d i S tl d i th l t 1950’ d d

e

tec

t

e

d in 

Scotlan

d in the la

te 1950’s an

d was 

in all 3 major commensal rodent species by the 1970’s.

• Beginning in the 1960’s, research efforts in the 

(1970’s), and elsewhere centered on detecting resistant populations and finding alternatives to resistant populations and finding alternatives to 

anticoagulants to which resistance had been de
Second-g g eneration Anticoagula

• Hydroxycoumarin compounds synthesized for 

purpose of finding agents having the use advaof anticoagulants plus the capacity to control populations resistant to the anticoagulants prepopulations resistant to the anticoagulants pre

used (later called “first-generation anticoagula

• Initial research showed such effects for difena

bromadiolone, brodifacoum.
2nd-Gen. Anticoagulants (con

nd-Gen. Anticoag (

ulants (con

• Animals feeding on baits containing second-gene

anticoag y

ulants were more likely than those feedi

other anticoagulants to ingest a lethal amount ovfirst 24 hours – a plus for efficacy and a minus fo

• So-call d “ i l lled “single-f di ” ff t l li d t 

feeding” effect also applied to n

incidents.

• Although Vitamin K1 oug a is antidotal, extended treatm

1 s a do a , e e ded ea 

regimens may be needed with 2nd-generation 

anticoagulants.
Anticoagulant Resistance in U

• Not well studied: no surveillance for ~30 years

VKORC1 mutants detected recently

• Not documented for 2nd-generation anticoagula

U S but has been elsewhere for some compoU.S. but has been elsewhere for some compo

• Resistant animals would be vulnerable to brom

cholecalciferol, zinc phosphide and to mechanmethods in addition to some or all 2nd-generati

anticoagulants. 
No 2nd-generation Anticoagulan

Cons mer Stores Consumer Stores

• No effects likely if local rodents are susceptible to 1st -ge

anti l t coagulants

• Other control approaches available, including rodenticid

are not anticoagulants

• Selection for resistance possible only where resistanceconferring alleles are present and only if selective press

sufficient (e.g., bait removes all susceptibles over wide 

• Consumer use of rodenticides unlikely to be well coordi

even within neighborhoods to exert sustained selective 
Efficacy Data Requirements f

Commensal Rodenticides

• Characterize lethalit

yg 

 of active in

gredient to tar

species: oral LD50 trials with wild-type of each species to be claimed

• D t l t bilit /l th lit f d ti id 

Documen

t pala

t

abilit

y/l

eth

ality o

f ro

denti

cide u

laboratory conditions: “choice” feeding trials wthe of each species to be claimed

• Document ability of rodenticide to control comm

rodenticide populations: field trials with each sto be claimed to be claimed
Field Efficacy Trials Field Efficacy Trials

• Existing infestations of target speci

Existing infestations of target speci

• Must be conducted as an experime• Pre

-treatment and post treatment and post

-treatment treatment

activity monitoring using at least tw

independent census methods independent census methods
New Bait Formulations fo

R i t d A ti I di Reg

i

s

tere

d

A

ctive 

Ingredien

• Laborator

y g choice feedin

g tests with wil

Norway rats and house mice, or with celaboratory strains if equivalency has beeestablished (the usual case)

• Penetration studies for placepacks

• Rarely, field trials for odd or perishable 

formulations.
Palatability in Choice Tes

Palatability Palatability in Choice Tes

• Bait and challenge diet are presented in equal 

amounts to test-group rodents at start of choicBoth are novel food items.

• Challenge diet is 65% whole yellow ground co

Challenge diet is 65% whole yellow ground co

ground rolled oat groats, 5% corn oil, and 5% powdered or confectioners sugar.

• Bait exposure periods are 1, 2, or 15 days long

depending upon protocol selected. 3-day baitexposure periods also have been used exposure periods also have been used.
Bait Form: Blocks vs. Pelle

• Commensal rodenticide bait formulations regis

U S t d ffi it i Th U.S. mee

t or excee

d efficacy criteria. The sam

criteria apply for blocks and pellets if baits are re

g yp istered for typical structural uses.

• Initial reluctance to recognize bait blocks as fo

been observed in some cases.

• Bait blocks secured in bait stations are less lik

be transported by rodents than are pellets or sunsecured bait blocks.
Efficacy Criteria

• Field Trials – at least 70% in reduction of pretreatment activity as determined through at lea

treatment activity as determined through at lea

independent census methods.

• Laboratory Trials -- >90% mortality of test grou

<10% mortality in control group. >33% bait 

acceptance (rejection <2:1 vs. challenge diet) 

t a s t ba t rials with bait-e posu e pe ods day o xposure periods >1 day for anticoagulants. Exceptions: >80% mortality an

>25% acceptance for weathered baits. 
Efficacy Bottom Lines Efficacy Bottom Lines

• Active in

g g redients are not re

gistered to 

commensal rodents unless control of alcommensal species claimed has been demonstrated under conditions of actua

• Bait formulations are not registered unle

th t it i f ffi i l b t they mee

t criteria 

for efficacy in la

bora

to

choice tests (or in field tests – an option 

seldom exercised) seldom exercised).
Conclusions

• Active ingredients in consumer ma

Active ingredients in consumer ma

post-RMD have met EPA’s efficacy 

criteria.

• Bait formulations in consumer mark

post

-RMD have met EPA RMD have met EPA s’ efficac

efficac

criteria.