United States Prevention, Pesticides EPA712-C-96-331
Environmental Protection and Toxic Substances February 1996
Agency (7101)
&EPA Microbial Pesticide
Test Guidelines
OPPTS 885.4150
Wild Mammal Testing,
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 885.4150 Wild mammal testing, Tier I.
(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-18. The toxicity
and pathogenicity data required for evaluating hazard to humans and do-
mestic animals are normally adequate to indicate potential hazard to wild
mammals. Under certain conditions, however, these data are not sufficient
to assess the potential hazard to wild mammals likely to be exposed to
a microbial pest control agent (MPCA). An example of one circumstance
when such additional testing may be required is the situation in which
data indicate that there is considerable variation in sensitivity of different
mammalian species to the effects of an MPCA agent, and there is evidence
that wild mammals will be heavily exposed to an MPCA. See 40 CFR
158.50 and 158.740(e) to determine whether these data must be submitted.
(b) Test standards. Data must be derived from tests that satisfy the
general test standards in OPPTS 885.0001 and the following:
(1) Test substance. The actual form of the material to be regarded
as the test substance is described in section OPPTS 885.0001. In addition,
any substances used to enhance virulence or toxicity should be tested along
with the test substance.
(2) Species. Testing shall be performed on a mammalian species rep-
resentative or indicative of those found in areas likely to be affected by
the proposed use patterns. Test animals may be reared in pens or captured
in the wild, and must be phenotypically indistinguishable from wild mam-
mals. Endangered or threatened animals shall not be used.
(3) Controls, (i) A negative control group is required.
(ii) A concurrent control group is required and shall be treated, when
possible, with the pure active ingredient that has been inactivated in such
a way as to preserve cellular integrity.
(4) Route of exposure. The test material should be administered by
gavage (acute oral dose) or by intranasal instillation. The method of dosing
should reflect the expected exposure route and shall be determined after
consultation with the Agency.
(5) Maximum hazard dosage level. The standards for maximum haz-
ard dosage level, determination of an LD50 or ID50, and duration of test
that are found in the avian oral pathogenicity/toxicity test OPPTS 885.4050
and the avian inhalation pathogenicity test OPPTS 885.4100.
(c) Reporting and evaluation of data. In addition to the information
specified in OPPTS 885.0001, test reports shall contain the same informa-
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tion required for the avian oral pathogenicity/toxicity test OPPTS 885.4050
and the avian inhalation pathogenicity test OPPTS 885.4100, adapted ap-
propriately for mammalian test procedures.
(d) Tier progression. (1) If any toxic or pathogenic effects on mam-
malian species are observed at the maximum hazard dosage level in this
study, testing at Tier II (OPPTS 885.5000, 885.5200, 885.5300, and
885.5400—environmental expression testing) is required as specified in
40 CFR 158.740(e). In some cases, a subchronic test may serve to better
understanding of the the effects observed at the Tier I level and alleviate
the need for Tier II testing.
(2) If toxic or pathogenic effects are not observed in this study, addi-
tional testing at higher tiers ordinarily is not required. The Agency may
require additional testing, however, if it determines that there is a potential
risk to mammals despite negative Tier I results.
(e) References. The following references are provided for use in the
development of test protocols for conducting wild mammal toxicity and
pathogenicity tests with microbial pest control agents:
(1) Barnes, R.W. et al. Long-term feeding and other toxicity/patho-
genicity studies on rats using a commercial preparation of the nuclear-
polyhedrosis virus of Heliothis zea. Journal of Invertebrate Pathology
16:112-115(1970).
(2) Fisher, R. and L. Rosner. Toxicology of the microbial insecticide,
Thuricide. Agricultural and Food Chemistry 7:686-688 (1959).
(3) Ignoffo, C.M. and A.M. Heimpel. The nuclear polyhedrosis virus
of Heliothis zea (Boddie) and Heliothis virescens (Fabricius) Part V. Tox-
icity-pathogenicity of virus to white mice and guinnea pigs. Journal of
Invertebrate Pathology 7:329-340 (1965).
(4) Ignoffo, C.M. Intraperitoneal injection of white mice with
nucleopolyhedrosis virus of the beet armyworm, Spodoptera exigua. Jour-
nal of Invertebrate Pathology 17:453-454 (1971).
(5) Ignoffo, C.M. Effects of entomopathogens on vertebrates. Annals
N.Y. Academy of Science 217:141-164 (1973).
(6) Ignoffo, C.M. et al. Lack of susceptibility of mice and rats to
the mosquito nematode, Reesimermis nielseni, Tsai and Grundmann. Mos-
quito News 34:425-428 (1974).
(7) Ignoffo, C.M. et al. An evaluation of the risks to mammals of
the use of an entomopathogenic fungus, Nomuraea rileyi, as a microbial
insecticide. In: Baculoviruses for Insect Pest Control: Safety Consider-
ations. Selected papers from EPA/USDA Working Symposium, American
Society of Microbiologists, Washington, DC (1975).
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(8) Lamanna, C. and L. Jones. Lethality for mice of vegetative and
spore forms of Bacillus cereus and Bacillus cereus-like insect pathogens
injected intraperitoneally and subcutaneously. Journal of Bacteriology
85:532-535 (1963).
(9) Lautenschlager, R.A.et al. Effect of nucleopolyhedrosis virus on
selected mammalian predators of the gypsy moth. USDA Forest Service
Research Papers, NE-377, 6p. (1977).
(10) Lautenschlager, R.A. and J.D. Podgwaite. Passage of
nucleopolyhedrosis virus by avian and mammalian predators of the gypsy
moth, Lymantria dispar. Environmental Entomology 8:210-214 (1979).
(11) Lautenschlager, R.A. and J.D. Podgwaite. Passage of infectious
nuclear-polyhedrosis virus through the alimentary tracts of two small mam-
mal predators of the gypsy moth, Lymantria dispar. Environmental Ento-
mology 6:737-738 (1977).
(12) Meinacke, C.F. et al. Toxicity-pathogenicity studies of a nuclear-
polyhedrosis virus of Heliothis zea in white mice. Journal of Invertebrate
Pathology 15:10-14 (1970).
(13) Summers, M., R. Engler, L.A. Falcon, and P. Vail, eds. Pp. 179-
184 In: Guidelines for Safety Testing of Baculoviruses Baculoviruses for
Insect Pest Control: Safety Considerations. American Society for Microbi-
ology Washington, DC (1975).
(14) Watts, D.M. et al. Experimental infection of vertebrates of the
Pocomoke Cypress Swamp, Maryland with Keystone and Jamestown Can-
yon viruses. American Journal of Tropical Medicine and Hygiene 28:344-
350 (1979).
(15) Wolf, K. Evaluation of the exposure of fish and wildlife to nu-
clear polyhedrosis and granulosis viruses. Pp. 109-111 In: Baculoviruses
for Insect Pest Control: Safety Considerations. American Society for
Microbiology, Washington, DC (1975).
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