United States       Prevention, Pesticides     EPA 712-C-98-411
         Environmental Protection    and Toxic Substances     March 1998
         Agency        (7101)
4»EPA   Product Performance
         Test Guidelines
         OPPTS 810.3300
         Treatments to Control
         Pests of Humans and
         Pets

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                           INTRODUCTION
     This guideline is one  of a  series  of test  guidelines that have been
developed by the Office of Prevention, Pesticides and Toxic Substances,
United States Environmental  Protection Agency for use  in the testing of
pesticides and toxic substances, and the  development of test data that must
be submitted to the Agency  for review under Federal regulations.

     The Office of Prevention, Pesticides and Toxic Substances (OPPTS)
has  developed this guideline through  a process of harmonization that
blended the testing  guidance  and requirements that  existed in the Office
of Pollution Prevention and  Toxics  (OPPT) and appeared in Title  40,
Chapter I,  Subchapter R of the Code of Federal Regulations  (CFR),  the
Office of Pesticide Programs (OPP) which appeared in publications of the
National Technical  Information Service (NTIS) and the guidelines pub-
lished by the Organization  for Economic Cooperation and Development
(OECD).

     The purpose of harmonizing these  guidelines  into a single set of
OPPTS  guidelines is to minimize variations among the testing procedures
that must be performed to meet the data  requirements of the U. S. Environ-
mental Protection Agency  under the Toxic  Substances  Control Act  (15
U.S.C. 2601) and the Federal Insecticide, Fungicide and Rodenticide Act
(7U.S.C. I36,etseq.).

     Final  Guideline Release: This guideline  is available from the U.S.
Government Printing Office, Washington, DC 20402 on The Federal Bul-
letin  Board.   By  modem  dial   202-512-1387,  telnet   and   ftp:
fedbbs.access.gpo.gov  (IP 162.140.64.19), or  call 202-512-0132 for disks
or paper copies.  This  guideline is also available electronically in ASCII
and PDF (portable document format) from EPA's World Wide Web  site
(http://www.epa.gov/epahome/research.htm) under the heading "Research-
ers and  Scientists/Test Methods and Guidelines/OPPTS  Harmonized Test
Guidelines."

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OPPTS 810.3300  Treatments to control pests of humans and pets.
     (a) Scope—(1) Applicability. This guideline is intended to meet test-
ing requirements of the Federal  Insecticide, Fungicide,  and Rodenticide
Act (FIFRA) (7 U.S.C. 136, et seq.)

     (2) Background. The source materials used in developing this har-
monized OPPTS test guideline are OPP guideline 95-9 Treatments to con-
trol pests  of humans  and pets and 95-30 Acceptable  methods (Pesticide
Assessment Guidelines, Subdivision G: Product Performance,  EPA report
540/9-82-026).

     (b) Overview. This guideline is  concerned with efficacy testing of
invertebrate control pesticides used on humans and pets.  Humans may be
infested by three types  of lice:  The body louse, the head louse, and crab
louse. The demonstration of effectiveness against any species should there-
fore  be based on tests against lice of  that particular type. Dogs and cats
are generally infested by lice, fleas, ticks, and the species used must be
fully identified in the report. There are many factors involved in actual
use conditions that testing cannot always adequately evaluate. The habits
of the host animals, infestation pressures of the parasite,  exposure to rain,
dew, sunlight, or even  pH of water and geographical considerations can
result in a change in the degree or duration  of efficacy for  a particular
product. In order to make label claims more meaningful, an accurate de-
scription of product performance under a broad spectrum  of use conditions
should be  recorded.

     (c) Definitions. The following definitions  apply to this guideline.

     Control animals. Those animals not treated with any pesticide prod-
uct.

     Placebo. A collar formulated from the same carrier matrix as the col-
lar to be tested, but lacking any active pesticide ingredients.

     Positive control.  A collar registered for  the  proposed label claims.

     Qualified personnel. Individuals who count or apply  the reinfestations
and are trained in finding and recognizing the parasites on the dog. They
should also be familiar with the biology of the parasite and the recording
techniques necessary in development of meaningful data.

     Test collar animals. Those animals wearing the collar which is under
evaluation.

     (d) General considerations—(1)  Number of trials. A minimum of
5 large-scale, geographically-prepared  trials are generally necessary, but
the number of trials can vary somewhat due to the accessibility of infesta-
tions, fluctuations in pest population pressures, behavior,  and other impor-
tant considerations in the biology of the target pest.

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     (2) Treatment techniques and equipment. Product  treatments to
control pests of humans are applied as sprays, dusts, lotions, towels, oint-
ments, creams, sticks, soaps, and shampoos. Product treatments to control
pests of pets are applied as sprays, dusts, foams, flea collars, flea tags,
soaps, and shampoos.

     (3) Evaluation and reporting considerations. Reports  should distin-
guish between killing and repelling effects, since repellent insecticides may
preclude any lethal effects. Insect repellency test  data should demonstrate
minimal contact between the insect and the test chemical. Any adverse
effects should be reported. Breed,  age, size, and hair length influence the
effectiveness of invertebrate  control  agents applied to  dogs  and cats, and
such factors must be evaluated and reported in testing pet treatments.

     (4) Toxicology tests. Any product intended to be applied directly to
humans or pets,  or  used so as to provide frequent or constant product
exposure to humans or pets, must be tested under the full range of toxi-
cology testing required in OPPTS guideline series 870, Health Effects Test
Guidelines. After submittal of such toxicology  data,  consultation with the
Agency is required before extensive product performance testing  dealing
with human pest control products is undertaken.

     (e) Suggested  performance  standards.  These  standards are pre-
sented on the basis  of pest population counts  from treated compared to
untreated subjects unless otherwise specified.

     (1) Pests of humans—(i) Body louse. Demonstrate 100% control of
the stage(s)  claimed to be controlled by the test product. Efficacy is based
on numbers of the body louse before treatment  and at intervals after treat-
ment, in tests conducted where  clothing, activities, and environments are
typical of those of louse-infested  populations.  Ovicidal activity must be
demonstrated unless repeat applications are intended.

     (ii) Head  louse and crab  louse. Demonstrate  100% control of the
stage(s) claimed to be controlled  by the  test product.  Efficacy is based
on  the numbers of eggs, nymphs and  adults of the head louse or crab
louse before and after treatment in  tests  conducted where  activities and
environments are typical of those  of louse-infested populations. Ovicidal
activity should be demonstrated unless repeat application are indicated.

     (iii) Ticks, fleas, and mites. Should provide  100% in pest infestation
through a killing or repelling action when tested under  simulated or actual
conditions. Or, the product  should provide the  protection time (in hours)
which is justified by the supporting data and  appears  on the label. The
minimum  acceptable protection time is one  hour, when using first con-
firmed bite methodology, or sock testing.

     (iv) Mosquitoes. Should generally provide a minimum of 2-3 hours
protection time based upon first confirmed bite field tests, depending upon

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the biting pressure evidenced in the testing. If the product provides longer
protection times, then this may be  stated on the label. Performance  stand-
ards for killing  mosquitoes are  listed under OPPTS 810.7400, Mosquito,
Black Fly, and Biting Midge (Sand Fly) Treatments.

     (v) Biting flies.  The data should indicate a minimum protection time
of 3 hours based upon  first  confirmed bite field tests. A product may be
registered for repelling biting  flies if it provides one to three hours of
protection, but the directions should be stated on the label.

     (2) Pests of pets (dogs, cats, birds)—(i) Fleas and ticks. Provide
90% reduction  in pest infestation through  a killing action when  tested
under simulated or actual field conditions.

     (A)  Guidance for the  testing of flea and tick collars for control
of ticks on dogs and cats—(7)  Scope. There are many commercially pro-
duced pesticidal matrices (as collars  and tags) which may now or  in the
future bear label claims for the control of fleas or ticks. Such claims are
acceptable only upon a demonstration of the efficacy of the product, as
claimed,  when used according to label directions. The strength and kind
of acceptable label  claims are generally determined by four factors  which
will be discussed later in greater detail. These  factors are:

     (/) The degree  of control against  fleas and ticks.

     (//) The anatomical coverage of the product.

     (///) The species  of parasites controlled.

     (/v) The duration of the control afforded.

This protocol is designed to  aid the investigator or registrant in the  devel-
opment of data  as it  applies to  the registration of various claims for im-
pregnated products, in such a manner as to include all of the above men-
tioned considerations.

     (2) Size of the test.  The test should be large enough to permit good
statistical evaluation.  The exact  number of animals to be evaluated cannot
be specifically stated. However,  the investigator is reminded that the valid-
ity of the results of the testing program is directly related to the degree
of variability  within  the  test. Increasing the number of test  animals in-
creases the  reliability of the test results.  In general, a minimum  of six
animals per group is required, with 10 preferred in any single test.

     (3) Selection of test arthropods—(/) Ticks. Limited or single species
testing may be utilized to  support restricted claims. For general tick control
claims, however, testing should be designed to show sufficient biological
activity to control those  species of ticks common to dogs.  Therefore, a
minimum amount of testing should  be conducted to ascertain  sufficient
activity against  representative tick species. In order to support  a general

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tick  claim, data must be derived on the brown dog tick (Rhipicephalus
sangulneus) and  at least one other species  of tick common to dogs. In
addition to the brown dog tick, other tick species common to dogs include
the lone star tick (Amblyoma americana), American dog tick (Dermacentor
variabilis)  and the Rocky Mountain wood tick (Dermacentor andersonf).
D. variabilis is preferred.

     (//) Fleas. The only  species  required to  be  tested is the cat flea,
Ctenocephalides fells.  This flea is  the predominant species on  both dogs
and cats. Mixed flea populations may be used providing that an adequate
infestation  of C. fells  is established on  the test animals  and the fleas of
different species are counted and recorded separately.

     (4) Characteristics of control. The magnitude of the infestation on
the control animals should be representative of the population as  estab-
lished by the screening procedures.  Test collar dogs will then be compared
to the controls by parasite count and body areas infested.  The  acceptance
of a collar for registration and ultimate control claims  allowed will be
dependent on a number of factors.  These may include the overall number
of fleas or ticks, the  number of live attached ticks and live fleas on the
test collar  dogs in comparison to  the  control  animals; and the positive
control animals.

     (5) Testing specifications. (/)  All testing shall be conducted on male
and female adult dogs of various sizes and hair lengths.

     (//) Placebo collars shall be used on the control animals.

     (///) The animals  should have  a clean bill of health substantiated by
a veterinarian and  should undergo a preconditioning  period  of at least
seven days before use. All animals should be washed with a non-residual
insecticidal shampoo before initiation of the testing.

     (/v) All  control and test collar dogs shall be prescreened for tick at-
tachment before initiation of the test. Only animals showing acceptable
tick attachment shall be used in the  study.

     (v) Any other insecticides used on or near the animals  during the
course of any testing period must be fully justified, including any effects
of such application on tick populations

     (v/) While not required, a positive control test using a collar registered
for tick control would serve as a standard  reference and  aid in the final
evaluation of the test collars.

     (v//) A minimum of 5 large dogs  (40  Ibs.) must be  represented in
the sum of the entire  series of tests submitted for registration.  It is rec-
ommended, that at  least 3 large  dogs be included  in each group in each
test.

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     (6} Exposure. (/) Adult parasites are recommended for infestation of
the control  and test  collar animals.  All ticks should  be of uniform  age
and feeding status (unfed) since the last moult.

     (//) There are several  basic methods for infesting dogs with fleas  and
ticks. Any of these may be acceptable in developing data for registration.
Regardless  of the infestation procedure, the primary  consideration is to
achieve adequate numbers of attached parasites with sufficient anatomical
distribution to allow evaluation of collar effectiveness. The infestation pro-
cedure should be refined to the extent that equal infestation pressures are
applied to both control and test  collar dogs.  In general, a  minimum of
3 ticks and/or 5 fleas  per dog (controls) are necessary for a valid test.

     (///) All animals should be housed individually in  holding enclosures.
The  holding environment  should  provide both indoor  and outdoor  expo-
sure.

     (fv) If the proposed label claims refer to the ability of the collar such
that performance is unaffected by washing, then the test collared  animals
should be bathed biweekly with a non-insecticidal shampoo.

     (7) Reinfestation. (/)  Since fleas and ticks will leave a dog in certain
situations regardless  of the presence of a collar, a reinfestation of  unfed
parasites must be made at  specific intervals during the testing. All  animals
should be reinfested periodically  following the initial infestation for the
entire period  of control proposed for the product. Frequent observations
as described below for the initial infestation should be recorded for each
subsequent  reinfestation.  The same  period of observation  (1-7  days)
should be utilized for these reinfestations, and  all remaining parasites
should be removed  at  the end of each counting period. The duration of
testing must be consistent with label claims; therefore,  infestation pressure
must be maintained throughout the entire period of control. It  is suggested
that  the  actual  testing  be  continued in excess  of the  label  claim  being
sought to  provide more confidence in the data derived.

     (if) The reinfestation pressure should be of sufficient degree to induce
an acceptable quantity of parasites to attach to the control animals.

     (///) The same collar  shall be used on an  animal  for the duration of
a study, and control  and test collar animals shall not be interchanged prior
to a reinfestation challenge.
        Observations. (/) All observations should be made  and records
maintained by qualified personnel.

     (//) A pretreatment inspection of all animals should be made to ascer-
tain  the number  of parasites  on the dogs prior to the installation of the
collars.

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     (///) The initial observations should be made soon  after inoculation
to ascertain the knockdown potential of the collar. This observation (usu-
ally  at 2 hours, once  again at  8 hours) is essential for a "fast acting"
claim if so desired by the registrant. It is realized that observations made
this  soon after inoculation  may affect the degree of  attachment  for the
first  counting period.

     (/v)  Frequent counts of parasites  are then  recorded (e.g.,  every 2-
3 days) after infestation for a period of 5-7 days or until substantial de-
tachment occurs after engorgement. These inspections  should indicate the
number,  sex, attachment and viability (living or dead) of the ticks along
with the  specific locations on the animals (head, neck, torso,  rump, legs,
feet). This information should  be recorded  in  conjunction  with the  age
of the collar for the particular day on which a  dog was inspected.  For
fleas; only the number of parasites need be recorded.

     (v) Records  should be  kept for each individual  animal, and the data
combined into tables which compare the various  test groups (test  collars,
controls,  positive control animals).

     (v/)  All parasites remaining on animal (both test  collar and control)
at the end of the counting period should be removed as  well as possible.

     (v//) All abnormal signs and symptoms during the  course of the study
shall be noted and recorded  for both control and test collar animals.

     (9) Evaluation and interpretation of data derived from testing.
The  strength and kind of acceptable level claims are  generally determined
by four factors:

     (/) The degree of control.

     (//) Anatomical sites of tick attachment.

     (Hi) The species of parasites tested.

     (/v) The duration of effectiveness.

     (v) Ticks, (a) First is  the  degree  of control afforded by the collar.
Such claims  as "control ticks"  must be supported by data which indicate
that  the collar will effectively reduce  substantial populations of ticks to
a level significantly below  that of the control. For all practical purposes,
this  would be control  to the extent that the user would not usually be
required to rely on other pesticides or methods of control during the time
period specified on the labeling. It is realized that 100% tick control will
rarely be achieved in  tests  where the outdoor exposure  may  provide for
a source  of additional  reinfestation. In general, 90% control  is a desirable
level of reduction, but even 80% control may support label claim under
certain circumstances.

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     (b) It is also realized that some benefit is derived from collars which
do not give  control of ticks, yet induce a consistent recognizable reduction
in the number of ticks  on the test animals  as  compared to  the  control
animals.  Label claims for  "aids in the control of ticks" are  appropriate
for such  products. A recognizable reduction is a  level of protection which
is evident not only upon statistical analysis but which would be apparent
to the purchaser of the  product  in actual use situations. A minimum of
50% reduction must be apparent for an "aids in control" claim.

     (c) The second area of consideration is the use of anatomical restric-
tion in those cases where  the  concentrations of pesticide generated  from
the collar matrix do  not control  ticks over the entire body of the  dog.
If anatomical restrictions  are  necessary,  they will be  added  to  the tick
claim. A familiar example could  be to specify control  "in the head and
neck area only."

     (d) As  stated in paragraph (e)(2)(i)(A)(3)(/) of this guideline, the spe-
cies of ticks tested will determine the label claims to be supported.

     (e) The final factor involved in the  interpretation of the data is the
duration  of testing as compared with efficacy.  Label claims must be justi-
fied by data which are derived from testing the collar for that period of
time which is to appear on product labeling.  Such data must at least  show
the collar to be  efficacious over the control period proposed for the prod-
uct.

     (/) Fleas. For fleas, a minimum of 90% control, as compared to the
counts on the placebo animals,  is required for the duration of testing. There
are no "aids in control"  claims or anatomical restrictions in regard to
claims for the control of fleas.

     (10} Other data. (/) Note that other kinds of data are also  considered
when evaluating the efficacy of a product.  Such information as pesticide
release rates, when accurately  measured and correlated with the effective
dosage of the active ingredient to ticks, may also be used.  Such data should
be derived from in vivo tests and reported as mg  active ingredient released
per day.  Additionally, consumer or veterinary testing is often utilized to
further indicate the performance of a collar.

     (//) This provisional protocol  is not designed to be the only acceptable
test methodology for the generation of applicable data.  It is merely one
acceptable method which attempts to resolve many of those items which
have  resulted in data which were unacceptable to support registration in
the past.

     (ii) Lice. Demonstrate 100% reduction in pest infestation through kill-
ing or repelling action when tested under simulated or actual field condi-
tions.

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     (iii) Mites. Provide 100% reduction in pest infestation through killing
or repelling action when tested under simulated or actual field conditions.
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