United States       Prevention, Pesticides     EPA712-C-96-332
          Environmental Protection    and Toxic Substances     February 1996
          Agency        (7101)
&EPA   Microbial Pesticide
          Test Guidelines
          OPPTS 885.4200
          Freshwater Fish Testing,
          Tier

-------
                           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."

-------
OPPTS 885.4200   Freshwater fish 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-19.

     (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 considered
as the test substance is described in OPPTS 885.0001.  In  addition,  any
substance used to enhance virulence or toxicity should be  tested along
with the test substance.

     (2) Test organisms,  (i)  Testing shall be performed on one fish spe-
cies,  preferable  the rainbow trout  if the  microbial pest control agent
(MPCA) has only a terrestrial use and direct aquatic exposure is not ex-
pected, or two fish  species,  preferably the bluegill sunfish  and rainbow
trout, when direct aquatic exposure is  anticipated. Other species  of  fish
may be used, but  a justification must be supplied based on  an increased
susceptibility to  the MPCA or ecological considerations that preclude the
use of recommended species.

     (ii) The following characteristics should guide species selection:

     (A) Fish species likely to prey upon or scavenge the target host orga-
nisms should be tested, when  applicable.

     (B) Testing of young fish is  preferable. Very young (not yet actively
feeding), spawning, or recently spent fish should not be used.

     (C) Fish should weigh between 0.5 and 5.0 g  and be from the same
year class.  The length of the longest fish should be no  more than twice
that of the shortest fish.

     (iii) Ten fish  per group  should be used in multiple group testing, 30
fish in single group testing.

     (3) Route of exposure,  (i) The test substance shall be  administered
as a suspension directly into the water (i.e. aqueous exposure).

     (ii) Additionally, the MPCA should be administered through the  oral
route of exposure, preferably through incorporation in standard fish food
or through the use  of infected insects.

     (4) Maximum hazard dose, (i) At a minimum, the concentration in
the test water (for aqueous  exposure)  should, whenever possible, be at
least  106 units/mL or  at least l,000x the maximum calculated pesticide
concentration in a 6-in layer of water immediately following a direct appli-

-------
cation to a 6-in layer of water, whichever is greater and attainable. Meas-
ures should be  taken to ensure that the initial concentration of the MPCA
is maintained throughout the test should be described.

     (ii) Feed used in the dietary  exposure should be supplemented with
the test substance  to achieve a microbial concentration per gram of food
of at least lOOx the calculated cell density per milliliter in a 6-in  layer
of water immediately following  a direct application to a  6-in  layer of
water.

     (5) Controls, (i) A negative, nondosed control group should be run
concurrently the test groups.

     (ii) A control group in which the fish are  exposed to sterile filtrate
from production cultures should be performed concurrently with the test
groups.

     (6) Test duration. The fish  should be observed for  a minimum of
30 days after dosing. If symptomatology is present at the 30th day, obser-
vation should  be  continued  until  recovery,  mortality,  or unequivocal
moribundity is established.

     (7) Treatment concentrations. A single, group of fish may be tested
at  the maximum hazard dose. If deleterious effects, due either to toxicity
or pathogenicity are observed, sequentially lower doses  should be  tested
as described in paragraph (b)(8) of this guideline.

     (8) Determination of LC50  or ID50. (i)  The study endpoint  must
be chosen to reflect the activity of the specific microorganism under test,
i.e. if an MPCA is  expected to produce a  toxin and has little or no infectiv-
ity, the  appropriate endpoint would be  mortality. If,  however, the  major
mechanism is pathogenicity,  a more appropriate endpoint would  be  overt
symptomatology.

     (ii) The data  should establish that the freshwater fish LC50, defined
as the dose required to kill 50 percent of the  test organisms, or IC50,
defined as the dose necessary to produce overt symptomatology in 50 per-
cent of the  test organisms,  is  greater than the  maximum hazard dosage
level. If the LC50 or IC50 is lower than the  hazard dose, an LC50 or
IC50 with confidence intervals should be  established.

     (c) Reporting and evaluation of data. In addition  to  information
meeting the general reporting requirements of OPPTS 885.0001, a report
of the results of a fish toxicity and infectivity test must include the follow-
ing:

     (1) LC50 or IC50 determination, including  all associated parameters,
e.g. slope, goodness of fit, etc., along with the raw mortality data.

-------
     (2) Detailed description  of the steps taken to determine microorga-
nism dissemination, replication, or survival in any test animals tissues, or-
gans, or fluids.

     (3) Detailed description of dilution water, including:

     (i) Sterilization method.

     (ii) Source.

     (iii) Chemical characteristics (e.g. dissolved oxygen content, pH, chlo-
rine  content, dissolved salts).

     (iv) Pretreatments (if any).

     (4) Detailed description of the test, including:

     (i) Design.

     (ii) Container size.

     (iii) Medium (e.g. depth and volume).

     (iv) Prophylactic treatments.

     (v) Number of organisms per treatment level.

     (vi) Loading (weight of organisms per unit volume of medium).

     (vii) Lighting,  acclimation,  and test temperatures  (averages  and
range).

     (viii) Amount of test substance administered by each route of expo-
sure.

     (ix) Any unusual feature of the test method.

     (5)  Detailed descriptions of methods (or references to established
methods) used for all chemical analyses of water for chemical content and
MPCA concentrations.

     (6) Detailed description  of methods used for  all  microbial analyses
of water, transport hosts and test organisms, and results of such analyses.

     (7) Detailed description of the effects of exposure to the test substance
including:

     (i) The criteria used to determine the effects.

     (ii) Percentages of test animals that died or showed symptomology.

     (iii) A summary of these observations.

                                  3

-------
     (8) Any additional relevant  information about the test or its results
that would assist in the determination of hazard potential.

     (d) Tier progression. (1) If  toxic or pathogenic effects are observed,
testing at Tier II (environmental expression testing (OPPTS 885.5000,
885.5200,  885.5300, 885.5400,)  is  required  as  specified  in  40  CFR
158.740(e). In some cases,  a  subchronic test may serve to better under-
standing  of the effects observed at the Tier I level and alleviate the need
for Tier II testing.

     (2) Further testing generally is not required if results of this study
do not indicate toxic or pathogenic effects.  The Agency may require addi-
tional testing if it determines  that there is  a potential risk to  fish despite
negative Tier I results.

     (e) References. The following may contain useful background infor-
mation for developing test protocols:

     (1) Standard Methods for  Examination of Water and Wastewater. 14th
Ed. American Public Health Association, Washington, DC (1975).

     (2) ASTM-Standard E 729-80, Practice for Conducting  Acute Tox-
icity Tests with Fishes,  Macroinvertebrates, and Amphibians. American
Society for Testing  and Materials,  1916  Race Street, Philadelphia, PA
19103.

     (3) Committee  an Methods  for  Toxicity  Tests with  Aquatic Orga-
nisms. Methods for acute toxicity tests with fish, macroinvertebrates, and
amphibians. USEPA Ecological Research Series, EPA 660/3-75-009. 61
pp. (1975).

     (4) Hetrick, P.M. et al.Increased  susceptibility of rainbow trout to in-
fectious hematopoietic necrosis virus after exposure to copper. Applied and
Environmental Microbiology 37:198-201 (1979).

     (5) Huang, E. and J.S. Pagano. Nucleic acid hybridization technology
and detection of proviral genomes. Chapter 13 in: The Atlas of Insect and
Plant Viruses, K.  Maramorosch, Ed. Academic Press, NY (1977).

     (6) Ignoffo, C.M. et al. Susceptibility of aquatic vertebrates and inver-
tebrates to the infective  stage of the mosquito nematode Reesimermis
nielseni. Mosquito News 33:599-602 (1973).

     (7)  Tamer,   M.F.  et  al. The  tissue  localization  of  Aeromonas
salmonicida in rainbow trout, Salmo gairdneri Richardson, following three
methods  of administration.  Journal of Fish Biology 25:  95-108  (1984).

-------