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OCR for page 355
Pesticide Resistance: Strategies and Tactics for Management.
1986. National Academy Press, Washington, D.C.
Case Histones of
Anticoagulant Resistance
WILLIAM B. JACKSON and A. DANIEL ASHTON
Genetic resistance to anticoagulant rodenticides by commensal
rodents (Rattus norvegicus, R. rattus, Mus musculusJ is widespread.
Where it occurs rats and mice are not readily controlled with first-
generation compounds. Second-generation anticoagulants, however,
are effective in most situations. The first evidence of resistance to
these compounds is now available. Management of rodent popula-
tions is importantfor aesthetic, economic, and public health reasons.
INTRODUCTION
Anticoagulant rodenticides introduced in the 1950s selected for resistance
within a decade, first in Norway rats (Rattus norvegicus) from Scotland
(Boyle, 1960) then elsewhere in the United Kingdom (Rowe and Redfern,
1966; Bentley, 1969; Greaves et al., 1973~; from many areas of Europe,
including the roof rat (R. rattus) and house mouse (Mus musculus) (Lund,
1964, 19724; and eventually the United States (Jackson et al., 19714.
More recently resistance has been confirmed in commensal rats in Japan
(Naganuma et al., 1981) and Australia (Saunders, 19781. In Malaysia the
Malay wood rat (R. tiomanicus) (C. H. Lee, Malaysian Agriculture Research
and Development Institute, personal communication, 1982) and R. r. diardii
(Lam et al., 1982; Lam, 1984) are involved.
The World Health Organization (WHO, 1970) initially defined a resistant
Norway rat as one that survived a 6-day, no-choice feeding test with 50
ppm warfarin bait. (Appropriate criteria were also specified for the roof rat
and house mouse.) These criteria were verified by breeding tests (Greaves
355
OCR for page 356
356 TACTICS FOR PREVENTION AND MANAGEMENT
me 1' : ~ !~- ~
, 1 ~
~ Y
\ \ OWL ,
, ~
, ..
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· Cities with resistant populations
of Norway rats
a Cities without resistant Norway
rat populations Identified
, ~a ~°
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FIGURE 1 Distribution of warfar~n-resistant Norway rat populations in the United States.
and Ayres, 19761; and additional collection criteria and minimum consump-
tion levels were added in the United States (Frantz, 19771. Field-test criteria
have also been developed (Drummond and Rennison, 1973; Bishop et al.,
19771.
In Europe resistant populations frequently were identified from rural sites.
The first United States finding was in a rural area, but most of the identified
sites in the United States have been urban (Jackson et al., 19751. A nationwide
survey in the United States to determine the extent of anticoagulant resistance
in rodents was facilitated under the U.S. Public Health Service Urban Rat
Control Program (Jackson et al., 1973, 1975; Jackson and Kaukeinen, 1976;
Jackson and Ashton, 1980; Jackson et al., 1985~. Forty-five of the 98 sites
sampled had resistant Norway rat populations (Figure 11. That most of the
sites were urban may well be a function of the rodenticide use patterns, but
more likely this results from congressional funding of urban rat-control pro-
grams.
The problem of mouse resistance is believed to be far greater than the rat
problem, partly from differences in mouse population dynamics and feeding
OCR for page 357
ANTICOAGULANT RESISTANCE
357
behavior. House mouse populations had such a high level of resistance in
Europe a decade ago that conventional anticoagulants were no longer rec-
ommended for mouse control. Our knowledge of this species in the United
States is meager. Ashton and Jackson ~ 1984) reported anticoagulant resistance
in mice in several areas, both urban and rural, but no comprehensive (na-
tionwide) examination of mouse resistance has been conducted (Table 11.
Canada also has reported mouse resistance (Cronin, 1979; Siddiqi and Blaine,
19821.
The following case histories illustrate the problems inherent in controlling
rat and mouse populations in both rural and urban settings. They will also
show how and why control programs, if done improperly, can create greater
problems.
CHICAGO
The Chicago Rat Control Program began in June 1952, although rodent
control efforts had begun years earlier. Developed as a tripartite program
(the Departments of Health, Streets and Sanitation, and Buildings), initial
treatments covered six of the city's 50 wards during the first six months of
operation. Early rodenticides were cyanide gas, red squill, and 0.025 percent
warfarin (1: 191. The warfarin toxicant-to-bait ratio was later reduced to 1:49
(0.01 percent), when a mixer for the warfarin bait became available locally.
(This level was probably insufficient to produce consistent mortality and
enhanced resistance selection.) The operational pattern was to move system-
atically, ward by ward, block by block, through the city.
During March 1953 the effectiveness of the poisoning program was ana-
lyzed. In one block eight of nine premises that had active colonies (27 total
burrows) before the poisoning operations still had colonies with evidence of
activity afterward (Jackson and Evans, 19531. Operational efforts varied over
the years. Our next analysis was in 1972 as part of the U.S. Public Health
Service Urban Rat Control Program. Rats collected from the Lawndale target
area during 1972 to 1974 were subjected to the WHO (1970) protocol for
determining rodent resistance. Of the 87 rats tested, 50 (57 percent) survived
(Environmental Studies Center, 1974~.
By 1978 rats had been tested from four wards; 75 percent resistance to
warfarin was found in three of the four wards. The trend continued at least
through 1982. The Englewood area (Table 2) in 1978 had a 43 percent
incidence of rat resistance, a figure similar to the Lawndale resistance pattern
of 1972 to 1974. It is likely that the proportion of resistant rats in the
Englewood population has since increased, but no subsequent collections
have been made.
The problems of resistance in Chicago were both socioeconomic and man-
agerial. Rodent infestations were most abundant in the lower socioeconomic
OCR for page 358
358
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OCR for page 359
ANTICOAGULANT RESISTANCE
TABLE 2 Summary of Norway Rats from Chicago,
Illinois, Subjected to WHO Test for Warfann Resistance
Number ofNumber of Percent
District Rats TestedRats Surviving Resistant
Austin 6244 71
Englewood 6930 43
Garf~eld 118 73
Lawndale 212152 72
SOURCE: Jackson and Ashton (1980).
359
areas, which were characterized by large transient populations, absentee
landlords, abundant garbage, and vacant lots and vandalized buildings. These
general conditions throughout several wards of the city provided abundant
food and harborage, which supported large rat infestations. In contrast nearby
areas with block clubs had overall cleaner alleys, neater back yards, and
fewer rats.
Managerial problems also helped increase resistance. Warfarin baits were
manufactured by city personnel and distributed throughout the neighbor-
hoods. The quality of the bait was generally poor and inconsistent. Battings
were usually insufficient to control rodents, since warfarin baits require
multiple feedings over several days, and blocks were often baited only once
a month. Large dogs were present in many yards so only areas along the
alleys were baited, while burrows adjacent to buildings and inside locked
fences were left untouched. Inside-building infestations generally were not
treated.
The systematic control program often gave way to political pressure, and
rodent battings were handled on a complaint rather than systematic basis.
Thus, particular premises would be baited, but the entire block or even the
adjacent premises would be left untouched. Red squill treatments, which
would have killed resistant rats, were only partially effective because of
induced bait shyness. Therefore, rodent control was never really achieved.
Cyanide gas operations provided visible (political) evidence of rodent control
but offered little overall reduction in rats, because gassings were confined
to burrows in alleyways or away from structures and domestic animals.
Gassing operations were also labor-intensive, requiring more manpower per
unit area than baiting. Other rodenticides, including Vacor and norbormide,
were used in the city, but with limited success; both compounds are no longer
registered for use in rodent control in the United States. Also in 1978 the
Centers for Disease Control (CDC, U.S. Public Health Service in Atlanta)
restricted the use of conventional anticoagulants in federal target areas, thus
leaving the city with only zinc phosphide as a toxicant tool.
Coincident with the federal program a major clean-up campaign was ini
OCR for page 360
360
TACTICS FOR PREVENTION AND MANAGEMENT
tiated in 1978. Vacant lots were cleared of old cars, garbage, and rubbish;
lids were provided for all of the SS-gallon drums that were used as garbage
cans. The program aimed at educating the public was left understaffed,
however, resulting in insufficient follow-up and emphasis on long-term en-
vironmental improvement.
These practices all fostered the increasing frequency of resistant rats. The
ineffective applications of anticoagulant baits meant that rats with the resistant
allele survived, and enough target-area rats remained to facilitate rapid breed-
ing. Populations quickly rebuilt, and when warfarin baits were distributed
again, resistant genotypes tended to be selected. After several years of such
operations, most rats in these areas were anticoagulant-resistant.
Rat Bites
The number of reported and confirmed rat bites hit a low of 90 in 1968,
reflecting a major clean-up campaign initiated in 1966 with the onset of
support from the federal rat-control program (Table 3~. Cases of rat bite
increased during the 1970s, however. They peaked in 1979, a result of heavy
snows hampering garbage pickup and facilitating an increase in the rodent
populations, combined with ineffective rat-control efforts due to an increase
in the incidence of resistance.
Second-Generation Anticoagulants
Brodifacoum, a second-generation anticoagulant, was registered for urban
use in 1979. By 1984 rodent activity had decreased 75 percent in much of
the area (Terry Howard, Chicago Sun Times, personal communication, 19841.
Better bait materials and better placement of baits contributed to the reduction,
as did the single-feeding characteristic of this rodenticide.
Many of the underlying problems that permitted the establishment of pop-
ulations resistant to warfarin, however, are still present. Since no rats were
collected in recent years for testing, the current incidence of resistance is
not known. The potential for development of resistance to the new second-
generation anticoagulants exists, and Chicago might well be the premier site
in the United States for identifying this phenomenon.
DECATUR
There have been few investigations of rural rodent resistance in the United
States, and most have been of mouse infestations. Although the number of
iRat bites usually are not uniformly reported, and any statistics concerning them should be used
cautiously. In Chicago, however, records are carefully maintained, and reported cases are investi-
gated. Consequently, these data are indicative of trends in rat populations.
OCR for page 361
ANTICOAGULANT RESISTANCE
TABLE 3 Summary of Number of Confirmed Rat Bite
Cases in Chicago, Illinois, from 1959 to 1982
Calendar Year
Number/Year
214
219
191
193
116
127
155
144
140
90
131
189
148
87
cat 200
323
240
177
156
1959
1960
1961
1962
1963
1964
1965
1966
1967
1968
1969
1970
1971
1972 (to Sept. 29)
1973-1978 (incl.)
1979
1980
1981
1982
SOURCE: Chicago Department of Health.
361
sites and sample sizes have been small, half of the mouse infestations have
had resistant mice. House mouse populations generally are confined to a
single building (or a single house in a city), and treatment patterns may vary
greatly. In agricultural sites such as poultry or hog farms, however, the
mouse infestations may be extensive.
Usually when a problem is identified the mouse population is well estab-
lished. Mouse movements tend to be vertical as well as horizontal; therefore,
large groups of mice can live in a relatively small area. Mouse population
dynamics can thus compound control efforts. When anticoagulants are used
mice from the "visible" population only are likely to encounter the bait.
Generally, the quantities of anticoagulant baits placed are insufficient to
control the infestation. Even if baits are maintained continuously for the
recommended 21 days, most mice will not encounter them.
In field tests mouse "waves" occur at approximately three-week intervals,
and in large populations in complex environments, several waves may occur
as mice are removed by poisoning (Ashton et al., 19831. Therefore, control
of such populations may take months. If bait is available for only three
weeks, the new immigrants may encounter only remnants of the bait, resulting
in sublethal doses and enhanced selection of the resistant gene. Such was
the case on a chicken farm near Decatur, Indiana.
OCR for page 362
362
TACTICS FOR PREVENTION AND MANAGEMENT
The farm was composed of three older, deep-litter grower houses. Main-
tenance in the buildings was minimal, and the feeding operation was
semiautomatic. Some grain was stored within the buildings. Mice had infested
the building for several years, and the farmer had treated with locally pro-
duced, low-quality warfarin bait. Considering the size of the mouse popu-
lation, the ample harborage and food to support a continuously breeding
population, and a poor-quality bait, the selection of resistant mice was only
a matter of time.
During one six-week period, 250 pounds of the poor-quality bait were
consumed without any apparent reduction in the mouse infestation. Labo-
ratory studies (conducted at the Bowling Green State University Rodent
Research Laboratory) of mice collected at the site revealed that 76 percent
were resistant to warfarin. Another site (Monroe, Indiana) had been treated
with the same bait for several years: 70 percent of the mice tested were
resistant to warfarin.
UNITED KINGDOM
Although the initial identification of warfarin resistance was in Scotland
(Boyle, 1960), most resistance sites were found in England and Wales (Greaves
and Rennison, 19731. Most were rural, although resistant rats apparently
spread from the initial site into nearby Glasgow, and Folkestone in south-
eastern England had a well-identified resistant urban population.
The best-studied resistant population was at a site on the Welsh-English
border near Welshpool. Initial efforts went into encircling and containing
the infested area using zinc phosphide as a toxicant. As the infested area
expanded 5 km/yr, however, defending the perimeter became increasingly
difficult and eventually was abandoned (Drummond, 1970~.
Resistance (involving all three species of commensal rodents) was docu-
mented in so many areas of the United Kingdom that field collections and
studies were discontinued. Use of anticoagulants in these resistant areas was
discouraged. Zinc phosphide was the prime alternative, and calciferol was
recommended for house mice; later, second-generation anticoagulants be-
came available. Some considered the resistant phenotypes to be at a repro-
ductive disadvantage once the selective pressure of anticoagulant use was
lifted (Bishop et al., 19771. In the absence of the rodenticide selection pres-
sure, the frequency of resistance decreased from 57 to 39 percent over several
years (Greaves et al., 19771.
Difenacoum (the first second-generation anticoagulant) use was initiated
in 1975. By the end of the decade resistance was widespread in Hampshire
in southern England: 14 percent of the rats tested (40 percent of the sites)
were resistant to the compound; 85 percent were resistant to warfarin. Prob
OCR for page 363
ANTICOAGUL4NT RESISTANCE
363
ably the distribution of difenacoum-resistant rats is more widespread than
the survey indicated (Greaves et al., 19821.
DATA BASE
Warfarin is a vitamin K antagonist; it inhibits the reduction of vitamin K
2,3-epoxide to vitamin K (Bell and Matschiner, 1972; Bell et al., 1972),
eventually blocking the vitamin K-regeneration enzyme system. This block-
ing inhibits the post-translational modification of prothrombin (carboxylation
of glutamic acid to ~y-carboxyglutamic acid) and eventual completion of the
bloodclotting sequence. Ultimately the animal dies from internal hemor-
rhaging.
Although the exact mechanism of warfarin resistance is still under inves-
tigation, a mutation probably occurs in warfarin-resistant animals at the active
site of the vitamin K-epoxide reductase, such that warfarin cannot compete
as effectively with vitamin K-epoxide. The cycle continues with y-carboxy-
glutamic acid being continuously supplied and subsequently producing nor-
mal prothrombin (Suttie, 1980; MacNicoll, 19811. MacNicoll (this volume)
has suggested some alternatives to the vitamin K-epoxide reductase mech-
anism.
Most investigators have determined resistance to be related to an autosomal
dominant allele (Greaves and Ayres, 19671. At one time resistance in the
house mouse was thought to be polygenic, but more recently, rat and mouse
resistance have been considered very similar (Wallace and MacSwiney, 19761.
In the United Kingdom, hypotheses of incomplete penetrance and modifier
genes have been expressed. Strains (based on geographic origin) have been
identified, and multiple allelism has been advanced to explain such variations
(Greaves and Ayres, 19821. In the laboratory, maintenance of resistant an-
imals requires diet supplementation with vitamin K. In natural populations
the heterozygote is considered to have survival advantage over the resistant
homozygote (Bishop and Hartley, 1976; Greaves et al., 19771. Because North
American resistant animals do not seem to require this vitamin K supple-
mentation, there may be several (or more) resistance genotypes. Research
and tests to identify these genetic variations, however, have not been carried
out.
Data Base United States
In the combined efforts at Bowling Green State University and the New
York State Department of Health, more than 10,000 Norway and roof rats
collected from over 100 locations have been examined (Jackson et al., 19851.
Nearly 50 Norway rat resistance sites have been identified, and the incidence
of resistance in most samples was less than 20 percent.
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364
TACTICS FOR PREVENTION AND MANAGEMENT
Warfarin-resistant house mice have been detected at 21 sites throughout
the country, but samples generally have been small. (Federal Rat project
funds could not be used for studies on mouse populations.) About half the
animals tested were resistant to warfarin, and 10 out of 11 urban samples
contained resistant mice. Thus, the mouse problem seems to be widespread
and critical in the United States.
Cross-Resistance
Norway rats and house mice have been tested against other first-generation
anticoagulant rodenticides. With Norway rats (from 16 locations in 13 cities
and 1 rural site) 165 out of 176 individuals (94 percent) resistant to warfarin
were also resistant to pival. Samples of warfarin-resistant house mice and
roof rats resistant to pival are small but definitive (five of five and two of
two, respectively). Tests for warfarin resistance on laboratory strain, pival-
resistant rats, however, produced mortality in 44 of 46 animals (Fukui, 19851.
Greaves and Ayres (1976) found a similar relationship between Welsh and
Scottish strains resistant to coumatetralyl, with the Welsh strain showing a
high resistance to warfarin and diphacinone. Different alleles probably are
responsible for this action (Greaves and Ayres, 19821. Following this logic
the pival-resistant strain should represent another allele, although this has
not been confirmed.
In general an animal resistant to warfarin is likely to survive (i.e., be
resistant to) feeding tests with any of the other hydroxycoumarin or indan-
dione compounds. Consequently, alternating first-generation rodenticides for
rodent control when resistance is suspected is not likely to be efficacious,
but rather may enhance selection of resistant populations.
MANAGEMENT
Second-Generation Anticoagulants
The new group of anticoagulants characterized as single-feeding (but with
delayed death) is a suitable tool for managing rodents. Brodifacoum and
bromadiolone have been marketed in the United States and elsewhere; di-
fenacoum, only outside the United States. These rodenticides kill rats and
mice resistant to first-generation compounds. Resistance to these second-
generation compounds has been found, however: in Canada, house mice
resistant to bromadiolone (Siddiqi and Blaine, 1982~; in England, Norway
rats resistant to difenacoum (Greaves et al., 19821; and in Denmark, bro-
madiolone resistance in rats (Lund, 1984~. Resistance to either second-gen-
eration compound in the United States has not been confirmed. There are
no published data as yet indicating brodifacoum resistance in natural popu
OCR for page 365
ANTICOAGULANT RESISTANCE
365
rations anywhere in the world, although an occasional laboratory rat has been
observed to survive a test with brodifacoum; similar observations have been
made in England with difenacoum-resistant strains (Lund, 1984; Cornwell,
1984; P. B. Cornwell, Rentokil, Ltd., East Grinstead, Great Britain, personal
communication, 19841.
Nonanticoagulant Alternatives
Alternative rodenticides (or other control tools) must be found when re-
sistance occurs. Acute (single-dose) rodenticides are not wholly acceptable.
Red squill is currently not available. Zinc phosphide is relatively hazardous
when not properly placed and quickly produces bait shyness.
A new chemical, bromethalin, was introduced commercially in December
1985 under the trade names "Vengeance" and "Assault." This rodenticide
is not an anticoagulant and acts after a single feeding. Although no further
feeding occurs, death is delayed several days. The compound kills antico-
agulant-resistant rodents (Jackson, 19851.
Another new compound, Quintox, was introduced in 1985; a form of
vitamin D (cholecalciferol), it disrupts calcium metabolism, producing hy-
percalcemia. It is effective against anticoagulant-resistant rodents and is sim-
ilar to the calciferol formulations long-used in Europe to control resistant
mice. Field-test efficacy data have not been published.
Alpha-chlorohydrin (Epibloc), a male sterilant, is toxic to resistant rats of
both sexes (Andrews and Belknap, 1983; Kassa and Jackson, 19841. It was
introduced as a restricted-use rodenticide, but has not been widely accepted
by pest control operators (PCOs). Other compounds, still in testing and
development modes by various companies, also have the potential for being
effective against resistant populations. The high costs of testing and data
acquisition now required for U. S. Environmental Protection Agency (EPA)
registration, however, may discriminate against their development for the
U. S. market.
Improving sanitation and repairing/proofing structures are long-term so-
lutions that have long been recognized as fundamental to managing pest
populations (Davis, 1953, 1972; NRC, 19801. Without them the effectiveness
of toxicants is reduced, and the selection pressure for resistance is increased.
With increased numbers of resistant rodents in our environment, the potential
for transmission of rodent-borne diseases is also increased. Concern for
resistance is important because of the public health significance, as well as
the depredations of these rodents to crops and stored products. Especially
when these rats and mice share our environment, the potential for transmission
to humans of many rodent-borne diseases is greatly increased. The clinical
forms of some of these diseases are just now being recognized (e.g., hem-
orrhagic fever with renal syndrome).
OCR for page 366
366
TACTICS FOR PREVENTION AND MANAGEMENT
PREDICTIONS AND RECOMMENDATIONS
· With the continued use of first-generation anticoagulants, resistant pop-
ulations will be selected with increasing frequency.
· Resistant house mouse populations especially are likely to increase in
frequency because of rodenticide use both by professionals and the public.
Because of the close association of this species to humans and the high
potential for food destruction and contamination, a serious public health,
economic, and aesthetic threat exists.
· Second-generation anticoagulants will find increasing markets. Resis-
tance can be expected in proportion to their market penetration because of
excessive placement of baits and failure to implement an integrated pest
management (IPM) program. Users should be strongly encouraged (through
training) in the prudent use of these rodenticides [e.g., pulsed baiting with
Talon (Dubock, 198211.
· Nonanticoagulant rodenticides (bromethalin, zinc phosphide, etc.), when
not used exclusively, should be alternated with anticoagulants at least an-
nually. Such use will mitigate against the selection and buildup of populations
resistant to either first- or second-generation anticoagulants.
· Resistant populations of the commensal rodent species can be demon-
strated readily. As agricultural and noncrop, nonurban uses of anticoagulants
expand, resistance in native rodents can be expected following several years
of persistent and careless or excessive distribution of baits.
RESEARCH NEEDS
· Commensal rodents (in the United States, these are Norway and roof
rats and house mice), in the absence of effective management tools and
efforts, will continue to pose serious public health problems, cause environ-
mental destruction and deterioration, and contaminate and consume signif-
icant proportions of grains, feeds, and food products. Rodents infesting
orchards and croplands can also-be selected for resistance with consequences
for serious economic losses. Quantification of such losses to individuals and
society are needed to determine cost/benefit patterns for management pro-
grams and to provide incentives for developing new tools.
· Studies of resistance incidence in the house mouse and native rodent
species have been neglected. Monitoring of resistant commensal rat popu-
lations should be continued and expanded in both agricultural and urban sites.
· The biochemical mechanisms) of resistance need continuing study.
Especially needed is support for breeding and maintenance of resistant strains
for research and genetic investigations of cross-resistance and the allelic
variations among different populations. (Since human anticoagulant resis
OCR for page 367
ANTICOAGULANT RESISTANCE
367
lance (O' Reilly et al., 1968) is an important consideration in treating vascular
problems, potential health benefits accrue as well.)
· In the future if anticoagulants are labeled by EPA for use in mainland
sugarcane (and other agricultural crops), the potential for selection of resis-
tance is present. Evaluation of existing Hawaiian populations, where anti-
coagulants have been used peripherally, would be useful.
· Strategies for rodent management, based on IPM principles, need to be
articulated and used. These will include environmental improvement, effec-
tive environmental education, and use (at least annually) of nonanticoagulant
rodenticides wherever monitoring indicates anticoagulant resistance exceeds
10 percent. In lieu of monitoring, such alternation of rodenticide types should
be part of the scheduled program.
· EPA registration procedures for experimental use permits, registration,
and reregistration of rodenticides should be made realistic (relative to the
characteristics and use patterns of the compounds), to stimulate commercial
development of new products.
ACKNOWLEDGMENTS
We are pleased to acknowledge funding assistance through the Urban Rat
Control Program (US PHS-CDC) for some of these studies. City of Chicago
personnel greatly facilitated our monitoring studies in Chicago. Staffs at both
the New York Health Department Laboratory at Troy and our own Bowling
Green State University Rodent Research Laboratory carried out the resistance
evaluation tests. Art Beeler was most helpful in allowing our access to his
buildings and mouse populations.
REFERENCES
Andrews, R. V. and R. W. Belknap. 1983. Efficacy of alpha-chlorhydrin in sewer rat control. J.
Hyg. (Camb.) 91 :359-366.
Ashton, A., and W. B. Jackson. 1984. Anticoagulant resistance in the house mouse in North America.
Pp. 181-188 in Proc. Conf. Organ. Pract. Vertebr. Pest Cont., A. C. Dubock, ed. Hampshire,
England: ICI Plant Protection Division.
Ashton, A., W. B. Jackson, and J. H. McCumber. 1983. An evaluation of methods used in
comparative field testing of commensal rodenticides. Pp. 138-154 in Vertebr. Pest Cont. Manage.
Mat.: Fourth Symp., ASTM STP 817, D. E. Kaukeinen, ed. Philadelphia, Pa.: American Society
for Testing and Materials.
Bell, R. G., and J. T. Matschiner. 1972. Warfarin and the inhibition of vitamin K by an oxide
metabolite. Nature (London) 237:32-33.
Bell, R. G., J. A. Sadowski, and J. T. Matschiner. 1972. Mechanism of action of warfarin. Warfarin
and metabolism of vitamin K. Biochem. 11:1959-1961.
Bentley, E. W. 1969. The warfarin resistance problem in England and Wales. Schriftenr. Ver.
Wasser., Boden, Lufthyg. Berlin-Dahlem 32:19-25.
Bishop, J. A., and D. J. Hartley. 1976. The size and age structure of rural populations of Rattus
OCR for page 368
368
TACTICS FOR PREVENTION AND MANAGEMENT
norvegicus containing individuals resistant to the anticoagulant poison warfarin. J. Anim. Ecol.
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Representative terms from entire chapter:
house mouse
