United States       Prevention, Pesticides     EPA712-C-96-342
          Environmental Protection    and Toxic Substances     February 1996
          Agency         (7101)
&EPA    Microbial Pesticide
          Test Guidelines
          OPPTS 885.4600
          Avian Chronic
          Pathogenicity and
          Reproduction Test, Tier

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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),    internet:     http://
fedbbs.access.gpo.gov, or call 202-512-0132 for disks  or paper copies.
This guideline is also available electronically in ASCII and PDF (portable
document format) from the EPA Public Access Gopher  (gopher.epa.gov)
under the heading "Environmental Test  Methods and Guidelines."

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OPPTS  885.4600  Avian chronic pathogenicity and reproduction
test, Tier III.
     (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 material used in developing this har-
monized OPPTS test guideline is OPP guideline 154A-26.

     (b) Purpose. The test in this guideline is intended to  determine if
chronic effects will occur  when animals are exposed to  low  levels of  the
microbial pest control agent  (MPCA) over an  extended period  of time.

     (c) Test standards. Data must satisfy the general test standards in
OPPTS 885.0001, and the following:

     (1) Test substance. The actual form of the material to be tested is
described in OPPTS 885.0001. In addition, any substances used to enhance
the virulence should be tested  along with the test substance.

     (2) Species.  Testing shall be performed on one avian species (pref-
erably the bobwhite quail  or mallard duck). The species selected shall be
the same as that used  for the avian inhalation pathogenicity test in OPPTS
885.4100.

     (3) Age. Birds approaching their first breeding season shall be used.

     (4) Controls. A  concurrent  control  group is  required and  shall  be
treated with inactivated MPCA.

     (5) Treatment levels. At  least two treatment levels shall be used.
The test concentrations should include an actual or expected field residue
exposure level and a multiple of that level such as 5x or lOx.

     (6) Dosing. The MPCA should be incorporated into the diet whenever
possible. The diet should be analyzed for MPCA viability and a new diet
should be prepared often  enough to ensure that the test animals  receive
a constant dose throughout the study.  Alternate routes  of dosing, along
with the rationale, should be discussed with the Agency. The registrant
should discuss with the Agency before starting this testing.

     (7) Number of birds per treatment group.  Each treatment group
should be replicated.  For bobwhite quail and mallard ducks,  a minimum
of 12 pen replicates for each treatment level should be used.

     (8) Duration of exposure. Birds shall be exposed to  treated diets
beginning not less than 10 weeks before  egg laying is expected, and  ex-
tending throughout the laying  season.

     (9) Duration of test. The test shall not end before  14 days after  the
last hatchling leaves the shell.

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     (d) Reporting and evaluation of data. In addition to the information
specified in OPPTS 885.0001, the test report shall contain the following
information:
     (1) Testing protocols.  All  methods used  in performing these tests
should be fully referenced or described in detail.
     (2) Test results. The following information  shall be reported for all
test groups:
     (i) Any observed abnormal behavior.
     (ii) All results of tests used to detect the presence of the MPCA.
     (iii) Time and date of mortalities.
     (iv) Results of gross necropsy tests conducted an all birds dying or
manifesting clinical symptomatology at test termination. Necropsies should
also be performed on at least 50 percent of the nonaffected birds.
     (v) Reisolation of microbes from  selected body tissues  that would
normally be affected by  an infection including the liver, kidney,  lungs,
spleen, cerebrospinal system, testes ovaries, oviducts, and gastrointestinal
tract and from all dead embryos,  and an assessment of the clinical signifi-
cance of such isolations.
     (vi) Morbidity.
     (vii) Accidental deaths or injuries.
     (viii) Observed clinical signs and symptoms.
     (3) Test conditions.  The following information shall be reported for
treated and untreated test groups:
     (i) Species.
     (ii) Age.
     (iii) Body weight.
     (iv) Number and sex  of birds in each treatment group.
     (v) Individual identification of birds.
     (vi) Diet composition and additives (especially antibiotics).
     (vii) Diet storage conditions and results of periodic assays for MPCA
content.
     (viii) Feed consumption (grams per day).
     (ix) Observation on palatability or repellency.
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     (x) Housing conditions of test birds:

     (A) Space allocations for mating and nesting.

     (B) Measures taken to ensure that the birds were protected from inju-
ries.

     (C) Lighting program, including hours per day and wattage or foot-
candles at bird level.

     (xi) Diagram of test layout.

     (xii) Temperature.

     (xiii) Water source and its microbiological and chemical characteris-
tics if sterilized distilled water is not used.

     (xiv) Pretest and  test history of the  test organisms with respect to
medical and chemical treatments.

     (4) Egg and hatching data. The following information shall be re-
ported for each treatment group:

     (i) Eggs laid (number of eggs per bird per day and per season).

     (ii) Hatching egg storage data.

     (A) Temperature.

     (B) Humidity.

     (C) Number of eggs placed in incubator.

     (D) Egg-turning frequency.

     (iii) Number of embryonated eggs.

     (iv) Number of embryos that hatch.

     (v) Ratio of hatched embryos to the number placed in the incubator.

     (vi) Number of dead embryos.

     (vii) Physical abnormalities in hatchlings.

     (viii) All observed clinical signs and symptoms.

     (ix) Post-hatchling mortality.

     (x) Weights of 14-day-old survivors.

     (5) Pesticide test data. The concentration of the MPCA in the  feed
must be monitored weekly, more often if MPCA viability is short, and

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the results tabulated. A statistically-sound sampling method should be em-
ployed for large quantities of treated feed.

     (e) Tier progression.  (1) If pathogenic and/or reproduction effects
are observed at actual or expected exposure levels:

     (i) The applicant should reconsider the proposed registration of the
product.

     (ii) The Agency will, at this time, review all the data and determine
if a decision regarding acceptability for registration should be made. Test-
ing at Tier IV, simulated or actual field testing (OPPTS 885.4900) may
not be feasible if adequate containment or quarantine methods are not pos-
sible. If they are,  testing  at Tier IV is required as specified by 40 CFR
158.740(e).

     (2) If no  pathogenic  effects are observed at actual or expected field
residues exposure levels, no additional testing is ordinarily required.

     (f) References. The following references are provided for use in the
development of test protocols for conducting chronic avian pathogenicity
and reproduction tests with microbial pest control agents:

     (1) Heinz, G.H. Methylmercury: Second year feeding effects on mal-
lard reproduction and duckling behavior. Journal of Wildlife  Management
40:82-90 (1976).

     (2) Heinz, G.H. and  L.N. Locks.  Brain lesions in mallard ducklings
from parents fed methylmercury. Avian Diseases 20:9-17 (1976).

     (3) Pesticide Assessment Guidelines Subdivision E—Hazard Evalua-
tion: Wildlife and Aquatic Organisms,  EPS-540/9-82-024, October  1982.

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