[Code of Federal Regulations]
[Title 40, Volume 30]
[Revised as of July 1, 2004]
From the U.S. Government Printing Office via GPO Access
[CITE: 40CFR797.1600]

[Page 121-132]
 
                   TITLE 40--PROTECTION OF ENVIRONMENT
 
         CHAPTER I--ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)
 
PART 797_ENVIRONMENTAL EFFECTS TESTING GUIDELINES--Table of Contents
 
                      Subpart B_Aquatic Guidelines
 
Sec. 797.1600  Fish early life stage toxicity test.

    (a) Purpose. This guideline is intended to be used for assessing the 
propensity of chemical substances to produce adverse effects to fish 
during the early stages of their growth and development. This guideline 
describes the conditions and procedures for the continuous exposure of 
several representative species to a chemical substance during egg, fry 
and early juvenile life stages. The Environmental Protection Agency 
(EPA) will use data from this test in assessing the potential hazard of 
the test substance to the aquatic environment.
    (b) Definitions. The definitions in section 3 of the Toxic 
Substances Control Act (TSCA) and the definitions in part 792--Good 
Laboratory Practice Standards, apply to this section. In addition, the 
following definitions are applicable to this specific test guideline:
    (1) ``Acclimation'' physiological or behavioral adaptation of 
organisms to one or more environmental conditions associated with the 
test method (e.g., temperature, hardness, pH).
    (2) ``Carrier'' solvent or other agent used to dissolve or improve 
the solubility of the test substance in dilution water.
    (3) ``Conditioning'' exposure of construction materials, test 
chambers, and testing apparatus to dilution water or to the test 
solution prior to the start of the test in order to minimize the 
sorption of test substance onto the test facilities or the leachig of 
substances from test facilities into the dilution water or the test 
solution.
    (4) ``Control'' an exposure of test organisms to dilution water only 
or dilution water containing the test solvent or carrier (no toxic agent 
is intentionally or inadvertently added).
    (5) ``Dilution water'' the water used to produce the flow-through 
conditions of the test to which the test substance is added and to which 
the test species is exposed.
    (6) ``Early life stage toxicity test'' a test to determine the 
minimum concentration of a substance which produces a statistically 
significant observable effect on hatching, survival, development and/or 
growth of a fish species continuously exposed during the period of their 
early development.
    (7) ``Embryo cup'' a small glass jar or similar container with a 
screened bottom in which the embryos of some species (i.e., minnow) are 
placed during the incubation period and which is normally oscillated to 
ensure a flow of water through the cup.
    (8) ``Flow through'' refers to the continuous or very frequent 
passage of fresh test solution through a test chamber with no recycling.
    (9) ``Hardness'' the total concentration of the calcium and 
magnesium ions in water expressed as calcium carbonate (mg 
CaCO3/liter).
    (10) ``Loading'' the ratio of biomass (grams of fish, wet weight) to 
the volume (liters) of test solution passing through the test chamber 
during a specific interval (normally a 24-hr. period).
    (11) ``No observed effect concentration (NOEC)'' the highest tested 
concentration in an acceptable early life stage test: (i) which did not 
cause the occurrence of any specified adverse effect (statistically 
different from the control at the 95 percent level); and (ii) below 
which no tested concentration caused such an occurrence.
    (12) ``Observed effect concentration (OEC)'' the lowest tested 
concentration in an acceptable early life stage test: (i) Which caused 
the occurrence of any specified adverse effect (statistically different 
from the control at the 95 percent level); and (ii) above which all

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tested concentrations caused such an occurrence.
    (13) ``Replicate'' two or more duplicate tests, samples, organisms, 
concentrations, or exposure chambers.
    (14) ``Stock solution'' the source of the test solution prepared by 
dissolving the test substance in dilution water or a carrier which is 
then added to dilution water at a specified, selected concentration by 
means of the test substance delivery system.
    (15) ``Test chamber'' the individual containers in which test 
organisms are maintained during exposure to test solution.
    (16) ``Test solution'' dilution water with a test substance 
dissolved or suspended in it.
    (17) ``Test substance'' the specific form of a chemical substance or 
mixture that is used to develop data.
    (c) Test Procedures--(1) Summary of test. (i) The early life stage 
toxicity test with fish involves exposure of newly fertilized embryos to 
various concentrations of a test substance. Exposure continues for 28 
days post hatch for the minnows and 60 days post hatch for the trout 
species. During this time various observations and measurements are made 
in a specific manner and schedule in order to determine the lowest 
effect and highest no-effect concentrations of the test substance.
    (ii) A minimum of five exposure (treatment) concentrations of a test 
substance and one control are required to conduct an early life stage 
toxicity test. The concentration of the test substance in each treatment 
is usually 50 percent of that in the next higher treatment level.
    (iii) For each exposure concentration of the test substance and for 
each control (i.e., regular control and carrier control is required) 
there shall be:
    (A) At least two replicate test chambers, each containing one or 
more embryo incubation trays or cups; and there shall be no water 
connections between the replicate test chambers;
    (B) At least 60 embryos divided equally in such a manner that test 
results show no significant bias from the distributions, between the 
embryo incubation trays or cups for each test concentration and control 
(i.e., 30 per embryo cup with 2 replicates);
    (C) All surviving larvae divided equally between the test chambers 
for each test concentration and control (e.g., 30 larvae per test 
chamber with 2 replicates).
    (iv) Duration. (A) For fathead minnow and sheepshead minnow a test 
begins when the newly fertilized minnow embryos (less than 48-hours old) 
are placed in the embryo cups and are exposed to the test solution 
concentrations. The test terminates following 28 days of post-hatch 
exposure, i.e., 28 days after the newly hatched fry are transferred from 
the embryo cups into the test chambers.
    (B) For brook trout and rainbow trout a test begins when newly 
fertilized trout embryos (less than 96-hours old) are placed in the 
embryo trays or cups and are exposed to the test solution 
concentrations. The test terminates following 60 days of post-hatch 
exposure (for an approximate total exposure period of 90 days).
    (C) For silverside a test begins with newly fertilized embryos (less 
than or equal to 48 hours old) and is terminated 28 days after hatching. 
The chorionic fibrils should be cut before randomly placing the embryos 
in the egg incubation cups.
    (2) [Reserved]
    (3) Range-finding test. (i) A range finding test is normally 
performed with the test substance to determine the test concentrations 
to be used in the early life stage toxicity test, especially when the 
toxicity is unknown. It is recommended that the test substance 
concentrations be selected based on information gained from a 4- to 10-
day flow-through toxicity test with juveniles of the selected test 
species.
    (ii) The highest concentration selected for the early life stage 
toxicity test should approximate the lowest concentration indicated in 
any previous testing to cause a significant reduction in survival. The 
range of concentrations selected is expected to include both observed 
effect and no-observed effect levels. The dilution factor between 
concentrations is normally 0.50, however, other dilution factors may be 
used as necessary.
    (4) Definitive test--(i) General. (A) A test shall not be initiated 
until after the test conditions have been met and

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the test substance delivery system has been observed functioning 
properly for 48-hours. This includes temperature stability, flow 
requirements of dilution water, lighting requirements, and the function 
of strainers and air traps included in the water-supply system, and 
other conditions as specified previously.
    (B) New holding and test facilities should be tested with sensitive 
organisms (i.e., juvenile test species or daphnids) before use to assure 
that the facilities or substances possibly leaching from the equipment 
will not adversely affect the test organisms during an actual test.
    (C) Embryos should be acclimated for as long as practical to the 
test temperature and dilution water prior to the initiation of the test.
    (D) When embryos are received from an outside culture source (i.e., 
rainbow and brook trout) at a temperature at variance with the 
recommended test temperature they shall be acclimated to the test 
temperature. When eggs are received, they should be immediately unpacked 
and the temperature of the surrounding water determined. Sudden 
temperature changes should be avoided. Acclimation to the appropriate 
test temperature should be accomplished within a period of 6 hours, and 
should incorporate the use of dilution water.
    (E) Embryos should be visually inspected prior to placement in the 
embryo cups or screen trays. All dead embryos shall be discarded. Dead 
embryos can be discerned by a change in coloration from that of living 
embryos (e.g., trout embryos turn white when dead). During visual 
inspection, empty shells, opaque embryos, and embryos with fungus or 
partial shells attached shall be removed and discarded. If less than 50 
percent of the eggs to be used appear to be healthy, all embryos in such 
a lot shall be discarded.
    (ii) Embryo incubation procedures. (A) Embryos can be distributed to 
the embryo cups or screen trays using a pipette with a large bore or a 
similar apparatus. Newly-hatched silverside fry are very sensitive to 
handling; the egg incubation cups should not be handled at all the first 
5 days after hatching begins. Just before hatching is expected to begin, 
the embryos should be transferred to clean incubation cups. Trout 
embryos can be distributed by using a small container which has been 
precalibrated to determine the approximate number of embryos it can 
hold; embryos are measured volumetrically in this manner, and are then 
poured onto the screen tray (or embryo cup). Trout embryos should be 
separated on the screen tray so that they are not in contact with each 
other. A final count will ensure the actual number on the screen tray. 
After random assignment, the screen trays or embryo cups are placed in 
the test chambers.
    (B) Each day until hatch the embryos are visually examined. Minnow 
embryos may be examined with the aid of a magnifying viewer. Trout 
embryos should not be touched. Trout embryos should be maintained in low 
intensity light or in darkness until 1-week post hatch, and are usually 
examined with the aid of a flashlight or under low intensity light. Dead 
embryos should be removed and discarded. Any embryos which are heavily 
infected with fungus shall be discarded and shall be subtracted from the 
initial number of embryos used as a basis for the calculations of 
percentage hatch.
    (C) When embryos begin to hatch they should not be handled.
    (iii) Initiation of fry exposure. (A) Forty-eight hours after the 
first hatch in each treatment level, or when hatching is completed, the 
live young fish shall be counted and transferred from each embryo cup 
into the appropriate test chamber. For silverside, all surviving fry are 
not counted until six days after hatching and are not transferred to 
embryo cups. All of the normal and abnormal fry shall be gently released 
into the test chamber by allowing the fry to swim out of each embryo 
cup; nets shall not be used. The trout embryos incubated on screen trays 
will hatch out in the test chambers, therefore handling of fish is not 
necessary.
    (B) If necessary, fry can be transferred from one replicate embryo 
cup to the other replicate within a test concentration to achieve equal 
numbers in each replicate chamber.
    (C) The number of live fry, live normal fry, live embryos, dead 
embryos and unaccounted for embryos for each

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cup shall be recorded when hatching is deemed complete. Those fry which 
are visibly (without the use of a dissecting scope or magnifying viewer) 
lethargic or grossly abnormal (either in swimming behavior or physical 
appearance) shall be counted. Late hatching embryos shall be left in the 
embryo cups to determine if they will eventually hatch or not. The range 
of time-to-hatch (to the nearest day) for each cup shall be recorded.
    (iv) Time to first feeding. (A) The first feeding for the fathead 
and sheepshead minnow fry shall begin shortly after transfer of the fry 
from the embryo cups to the test chambers. Silversides are fed the first 
day after hatch. Trout species initiate feeding at swim-up. The trout 
fry shall be fed trout starter mash three times a day ad libitum, with 
excess food siphoned off daily. The minnow fry shall be fed live newly-
hatched brine shrimp nauplii (Artemia salina) at least three times a 
day.
    (B) For the first seven days, feeding shall be done at minimum 
intervals of four hours (i.e., 8 am, 12 noon, and 4 pm); thereafter the 
fry shall be fed as indicated below.
    (v) Feeding. (A) The fathead and sheepshead minnow fry shall be fed 
newly hatched brine shrimp nauplii for the duration of the test at 
approximately 4-hour intervals three times a day during the week and 
twice on the weekend after the first week. Trout fry shall be fed at 
similar intervals and may receive live brine shrimp nauplii in addition 
to the trout starter food after the first week. Between days 1 and 8 
after first hatching, silverside fry are fed the rotifer, Brachionus 
plicatilis, three times daily at a concentration of 5,000 to 10,000 
organisms per egg cup (based on 15 fish/cup). From days 9 to 11, the fry 
shall be fed approximately 2,500 newly hatched brine shrimp (Artemia) 
nauplii and 5,000 to 10,000 rotifers twice daily. For the remainder of 
the test, the fish will be fed brine shrimp exclusively. The number of 
organisms used should be gradually increased to approximately 5,000 
nauplii by test day 28.
    (B) An identical amount of food should be provided to each chamber. 
Fish should be fed ad libitum for 30 minutes with excess food siphoned 
off the bottom once daily if necessary.
    (C) Fish should not be fed for the last 24 hours prior to 
termination of the test.
    (vi) Carriers. Water should be used in making up the test stock 
solutions. If carriers other than water are absolutely necessary, the 
amount used should be the minimum necessary to achieve solution of the 
test substance. Triethylene glycol and dimethyl formamide are preferred, 
but ethanol and acetone can be used if necessary. Carrier concentrations 
selected should be kept constant at all treatment levels.
    (vii) Controls. Every test requires a control that consists of the 
same dilution water, conditions, procedures, and test organisms from the 
same group used in the other test chambers, except that none of the test 
substance is added. If a carrier (solvent) is used, a separate carrier 
control is required in addition to the regular control. The carrier 
control shall be identical to the regular control except that the 
highest amount of carrier present in any treatment is added to this 
control. If the test substance is a mixture, formulation, or commercial 
product, none of the ingredients is considered a carrier unless an extra 
amount is used to prepare the stock solution.
    (viii) Randomization. The location of all test chambers within the 
test system shall be randomized. A representative sample of the test 
embryos should be impartially distributed by adding to each cup or 
screen tray no more than 20 percent of the number of embryos to be 
placed in each cup or screen tray and repeating the process until each 
cup or screen tray contains the specified number of embryos. 
Alternatively, the embryos can be assigned by random assignment of a 
small group (e.g., 1 to 5) of embryos to each embryo cup or screen tray, 
followed by random assignment of a second group of equal number to each 
cup or tray, which is continued until the appropriate number of embryos 
are contained in each embryo cup or screen tray. The method of 
randomization used shall be reported.
    (ix) Observations. During the embryo exposure period observations 
shall be made to check for mortality. During

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the exposure period of the fry, observations shall be made to check for 
mortality and to note the physical appearance and behavior of the young 
fish. The biological responses are used in combination with physical and 
chemical data in evaluating the overall lethal and sublethal effects of 
the test substance. Additional information on the specific methodology 
for the data obtained during the test procedure are discussed in the 
following sections.
    (x) Biological data. (A) Death of embryos shall be recorded daily.
    (B) When hatching commences, daily records of the number of embryos 
remaining in each embryo cup are required. This information is necessary 
to quantify the hatching success. A record of all deformed larvae shall 
be kept throughout the entire post-hatch exposure. Time to swim-up shall 
be recorded for the trout. Upon transfer of fry from the embryo cups to 
the test chambers, daily counts of the number of live fish should be 
made. At a minimum, live fish shall be counted on days 4, 11, 18, 25 and 
(weekly thereafter for the trout species) finally on termination of the 
test.
    (C) The criteria for death of young fish is usually immobility, 
especially absence of respiratory movement, and lack of reaction to 
gentle prodding. Deaths should be recorded daily and dead fish removed 
when discovered.
    (D) Daily and at termination of the test, the number of fish that 
appear (without the use of a magnifying viewer) to be abnormal in 
behavior (e.g., swimming erratic or uncoordinated, obviously lethargic, 
hyperventilating, or over excited, etc.) or in physical appearance 
(e.g., hemorrhaging, producing excessive mucous, or are discolored, 
deformed, etc.) shall be recorded and reported in detail.
    (E) All physical abnormalities (e.g., stunted bodies, scoliosis, 
etc.) shall be photographed and the deformed fish which die, or are 
sacrificed at the termination of the test, shall be preserved for 
possible future pathological examination.
    (F) At termination, all surviving fish shall be measured for growth. 
Standard length measurements should be made directly with a caliper, but 
may be measured photographically. Measurements shall be made to the 
nearest millimeter (0.1 mm is desirable). Weight measurements shall also 
be made for each fish alive at termination (wet, blotted dry, and to the 
nearest 0.01 g for the minnows and 0.1 g for the trout). If the fish 
exposed to the toxicant appear to be edematous compared to control fish, 
determination of dry, rather than wet, weight is recommended.
    (G) Special physiological, bio chem ical and histological 
investigations on embryos, fry, and juveniles may be deemed appropriate 
and shall be performed on a case by case basis.
    (5) Test results. (i) Data from toxicity tests are usually either 
continuous (e.g. length or weight measurements) or dichotomous (e.g. 
number hatching or surviving) in nature. Several methods are available 
and acceptable for statistical analysis of data derived from early life 
stage toxicity tests; however, the actual statistical methodology to 
analyze and interpret the test results shall be reported in detail.
    (ii) The significance level for all statistical testing shall be a 
minimum of P=0.05 (95 percent confidence level).
    (A) Example of statistical analysis. (1) Mortality data for the 
embryonic stage, fry stage and for both stages in replicate exposure 
chambers should first be analyzed using a two-way analysis of variance 
(ANOVA) with interaction model. This analysis will determine if 
replicates are significantly different from each other. If a significant 
difference between replicates or a significant interaction exists, cause 
for the difference should be determined. Modification should then be 
made in the test apparatus or in handling procedures for future toxicity 
tests. Further calculations should incorporate the separation of 
replicates. If no significant difference is observed, replicates may be 
pooled in further analyses.
    (2) After consideration of replicate responses, mortality data 
should then be subjected to one-way ANOVA. The purpose of this analysis 
is to determine if a significant difference exists in the percentage 
mortality between control fish and those exposed to the test material.

[[Page 126]]

    (3) If the one-way ANOVA results in a F ratio that is significant, 
it would be acceptable to perform t-tests on the control versus each 
concentration. A second technique is to identify treatment means that 
are significantly different; this method should involve the additional 
assumption that the true mean response decreases generally with 
increasing concentration. The researcher may also be interested in 
determining significant differences between concentrations.
    (4) Growth data should also be analyzed by one-way ANOVA with the 
inclusion of a covariate to account for possible differences in growth 
of surviving fry in embryo cup(s) that contain fewer individuals. This 
condition can occur in cases when the same amount of food is given to 
each test chamber regardless of the number of survivors.
    (B) Test data to be analyzed. Data to be statistically analyzed are:
    (1) Percentage of healthy, fertile embryos at 40-48 hours after 
initiation of the test. Percentage is based upon initial number used.
    (2) Percentage of embryos that produce live fry for release into 
test chambers. Percentage is based on number of embryos remaining after 
thinning.
    (3) Percentage of embryos that produce live, normal fry for release 
into test chambers. Percentage is based upon number of embryos remaining 
after thinning.
    (4) Percentage of fry survival at swim-up for trout. Percentage is 
based upon number of embryos remaining after thinning.
    (5) Percentage of embryos that produce live fish at end of test. 
Percentage is based upon number of embryos remaining after thinning.
    (6) Percentage of embryos that produce live, normal fish at end of 
test. Percentage is based upon number of embryos remaining after 
thinning.
    (7) Weights and lengths of individual fish alive at the end of the 
test.
    (C) It is important that fish length and weight measurements be 
associated with individual test chambers since the density of the fish 
and available food should be considered in the growth of the organism.
    (iii) Acceptability criteria. (A) An early life stage toxicity test 
is not acceptable unless at least one of the following criteria is 
significantly different (p=0.05) from control organisms when compared 
with treated organisms, and the responses are concentration-dependent: 
mortality of embryos, hatching success, mortality of fry (at swim-up for 
trout), total mortality throughout the test, and growth (i.e. weight). 
If no significant effects occur, but the concentrations tested were the 
highest possible due to solubility or other physio-chemical limitations, 
the data will be considered for acceptance.
    (B) In addition to obtaining significant effects on the exposed test 
species, a measure of acceptability in the response of control fish is 
also required.
    (C) A test is not acceptable if the average survival of the control 
fish at the end of the test is less than 80 percent or if survival in 
any one control chamber is less than 70 percent. For silversides, a test 
is not acceptable if the average overall survival of the control embryos 
and fish at the end of the test is less than 60 percent.
    (D) If a carrier is used, the criteria for effect (mortality of 
embryos and fry, growth, etc.) used in the comparison of control and 
exposed test organisms shall also be applied to the control and control 
with carrier chambers. For the test to be considered acceptable, no 
significant difference shall exist between these criteria.
    (E) A test is not acceptable if the relative standard deviation 
(RSD=100 times the standard deviation divided by the mean) of the 
weights of the fish that were alive at the end of the test in any 
control test chamber is greater than 40 percent.
    (6) Analytical measurements--(i) Analysis of water quality. 
Measurement of certain dilution water quality parameters shall be 
performed every 6 months, to determine the consistency of the dilution 
water quality. In addition, if data in 30-day increments are not 
available to show that freshwater dilution water is constant, 
measurements of hardness, alkalinity, pH, acidity, conductivity, TOC or 
COD and particulate matter should be conducted once a week in the 
highest test substance concentration. Measurement of

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calcium, magnesium, sodium, potassium, chloride, and sulfate is 
desirable.
    (ii) Dissolved oxygen measurement. The dissolved oxygen 
concentration shall be measured in each test chamber at the beginning of 
the test and at least once weekly thereafter (as long as live organisms 
are present) in two replicates of the control and the high, medium, and 
low test substance concentrations.
    (iii) Temperature measurement. Temperatures shall be recorded in all 
test chambers at the beginning of the test, once weekly thereafter and 
at least hourly in one test chamber. When possible, the hourly 
measurement shall be alternated between test chambers and between 
replicates.
    (iv) Test substance measurement. (A) Prior to the addition of the 
test substance to the dilution water, it is recommended that the test 
substance stock solution be analyzed to verify the concentration. After 
addition of the test substance, the concentration of test substance 
should be measured at the beginning of the test in each test 
concentration and control(s), and at least once a week thereafter. Equal 
aliquots of test solution may be removed from each replicate chamber and 
pooled for analysis. If a malfunction in the delivery system is 
discovered, water samples shall be taken from the affected test chambers 
immediately and analyzed.
    (B) The measured concentration of test substance in any chamber 
should be no more than 30 percent higher or lower than the concentration 
calculated from the composition of the stock solution and the 
calibration of the test substance delivery system. If the difference is 
more than 30 percent, the concentration of test substance in the 
solution flowing into the exposure chamber (influent) should be 
analyzed. These results will indicate whether the problem is in the 
stock solution, the test substance delivery system or in the test 
chamber. Measurement of degradation products of the test substance is 
recommended if a reduction of the test substance concentration occurs in 
the test chamber.
    (v) Sampling and analysis methodology. (A) Generally, total test 
substance measurements are sufficient; however, the chemical 
characteristics of the test substance may require both dissolved and 
suspended test substance measurements.
    (B) For measurement of the test substance, water samples shall be 
taken midway between the top, bottom, and sides of the test chamber and 
should not include any surface scum or material stirred up from the 
bottom or sides. Samples of test solutions shall be handled and stored 
appropriately to minimize loss of test substance by microbial 
degradation, photodegradation, chemical reaction, volatilization, or 
sorption.
    (C) Chemical and physical analyses shall be performed using 
standardized methods whenever possible. The analytical method used to 
measure the concentration of the test substance in the test solution 
shall be validated before the beginning of the test. At a minimum, a 
measure of the accuracy of the method should be obtained on each of two 
separate days by using the method of known additions, and using dilution 
water from a tank containing test organisms. Three samples should be 
analyzed at the next-to-lowest test substance concentration. It is also 
desirable to study the accuracy and precision of the analytical method 
for test guideline determination by use of reference (split) samples, or 
in ter lab or a tory studies, and by comparison with alternative, 
reference, or corroborative methods of analysis.
    (D) An analytical method is not acceptable if likely degradation 
products of the test substance, such as hydrolysis and oxidation 
products, give positive or negative interferences, unless it is shown 
that such degradation products are not present in the test chambers 
during the test. In general, atomic absorption spectrophotometric 
methods for metals and gas chro ma to graphic methods for organic com 
pounds are pre fer able to colori metric methods.
    (E) In addition to analyzing samples of test solution, at least one 
reagent blank also should be analyzed when a reagent is used in the 
analysis. Also, at least one sample for the method of known additions 
should be prepared by adding test substance at the concentration used in 
the toxicity test.

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    (d) Test conditions--(1) Test species. (i) One or more of the 
recommended test species will be specified in rules under part 799 of 
this chapter requiring testing of specific chemicals. The recommended 
test species are:
    (A) Fathead minnow (Pimephales promelas Rafinesque).
    (B) Sheepshead minnow (Cyprinodon variegatus).
    (C) Brook trout (Salvelinus fontinalis).
    (D) Rainbow trout (Salmo gairdneri).
    (E) Atlantic silverside (Menidia menidia).
    (F) Tidewater silverside (Menidia peninsulae).
    (ii) Embryos used to initiate the early life stage test shall be 
less than 48 hours old for the fathead and sheepshead minnows, 
silversides, and less than 96 hours old for the brook trout and rainbow 
trout. In addition, the following requirements shall be met:
    (A) All embryos used in the test shall be from the same source. 
Embryos shall be obtained from a stock cultured in-house when possible, 
and maintained under the same parameters as specified for the test 
conditions. When it is necessary to obtain embryos from an external 
source, caution should be exercised to ensure embryo viability and to 
minimize the possibility of fungal growth. A description of the brood 
stock history or embryo source shall be made available to EPA upon 
request.
    (B) Test species shall be cared for and handled properly in order to 
avoid unnecessary stress. To maintain test species in good condition and 
to maximize growth, crowding shall be prevented, and the dissolved 
oxygen level shall be maintained near saturation.
    (C) Embryos and fish shall be handled as little as possible. Embryos 
shall be counted and periodically inspected until hatching begins. When 
larvae begin to hatch, they shall not be handled. Transfer of minnow 
larvae from embryo cups to test chambers shall not involve the use of 
nets. No handling is necessary following introduction into the test 
chambers until termination of the test.
    (D) If fathead minnow embryos are obtained from in-house culture 
units, the embryos should be gently removed from the spawning substrate. 
The method for separating the fertilized eggs from the substrate is 
important and can affect the viability of the embryos; therefore the 
finger-rolling procedure is recommended.
    (E) Disease treatment. Chemical treatments to cure or prevent 
diseases should not be used before, and should not be used during a 
test. All prior treatments of brood stock should be reported in detail. 
Severely diseased organisms should be destroyed.
    (2) Test facilities--(i) Construction materials. Construction 
materials and equipment that contact stock solutions, test solutions, or 
dilution water into which test embryos or fish are placed should not 
contain any substances that can be leached or dissolved into aqueous 
solutions in quantities that can affect test results. Materials and 
equipment that contact stock or test solutions should be chosen to 
minimize sorption of test chemicals from dilution water. Glass, 
316 stainless steel, nylon screen and perfluorocarbon plastic 
(e.g., Teflon) are acceptable materials. Concrete or rigid 
(unplasticized) plastic may be used for holding and acclimation tanks, 
and for water supply systems, but they should be thoroughly conditioned 
before use. If cast iron pipe is used in freshwater supply systems, 
colloidal iron may leach into the dilution water and strainers should be 
used to remove rust particles. Natural rubber, copper, brass, galvanized 
metal, epoxy glues, and flexible tubing should not come in contact with 
dilution water, stock solutions, or test solutions.
    (ii) Test chambers (exposure chambers). (A) Stainless steel test 
chambers should be welded or glued with silicone adhesive, and not 
soldered. Glass should be fused or bonded using clear silicone adhesive. 
Epoxy glues are not recommended, but if used ample curing time should be 
allowed prior to use. As little adhesive as possible should be in 
contact with the water.
    (B) Many different sizes of test chambers have been used 
successfully. The size, shape and depth of the test chamber is 
acceptable if the specified flow rate and loading requirements can be 
achieved.
    (C) The actual arrangement of the test chambers can be important to 
the statistical analysis of the test data.

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Test chambers can be arranged totally on one level (tier) side by side, 
or on two levels with each level having one of the replicate test 
substance concentrations or controls. Regardless of the arrangement, it 
shall be reported in detail and considered in the data analysis.
    (iii) Embryo incubation apparatus. (A) Recommended embryo incubation 
apparatus include embryo cups for the minnow species and screen trays 
for the trout species, although embryo cups can be used for the trout 
species. Embryo cups are normally constructed from approximately 4-5 cm 
inside diameter, 7-8 cm high, glass jars with the end cut off or similar 
sized sections of polyethylene tubing. One end of the jar or tubing is 
covered with stainless steel or nylon screen (approximately 40 meshes 
per inch is recommended). Embryo cups for silversides are normally 
constructed by using silicone adhesive to glue a 10-cm high, 363-um 
nylon mesh tube inside a 9-cm I.D. glass Petri dish bottom. The embryo 
cups shall be appropriately labeled and then suspended in the test 
chamber in such a manner as to ensure that the test solution regularly 
flows through the cup and that the embryos are always submerged but are 
not agitated too vigorously. Cups may be oscillated by a rocker arm 
apparatus with a low rpm motor (e.g., 2 rpm) to maintain the required 
flow of test water. The vertical-travel distance of the rocker arm 
apparatus during oscillation is normally 2.5-4.0 cm. The water level in 
the test chambers may also be varied by means of a self-starting siphon 
in order to ensure exchange of water in the embryo cups.
    (B) The trout embryo incubation trays can be made from stainless 
steel screen (or other acceptable material such as plastic) of about 3-4 
mm mesh. The screen tray should be supported above the bottom of the 
test chamber by two folds of screen or other devices which function as 
legs or supports. The edges of the screen tray should be turned up to 
prevent bump spills and to prevent the embryos from rolling off in the 
event of excessive turbulence. Suspending or supporting the screen tray 
off the bottom ensures adequate water circulation around the embryos and 
avoids contact of embryos with possible bottom debris.
    (iv) Test substance delivery system. (A) The choice of a specific 
delivery system depends upon the specific properties and requirements of 
the test substance. The apparatus used should accurately and precisely 
deliver the appropriate amount of stock solution and dilution water to 
the test chambers. The system selected shall be calibrated before each 
test. Calibration includes determining the flow rate through each 
chamber, and the proportion of stock solution to dilution water 
delivered to each chamber. The general operation of the test substance 
delivery system shall be checked at least twice daily for normal 
operation throughout the test. A minimum of five test substance 
concentrations and one control shall be used for each test.
    (B) The proportional diluter and modified proportional diluter 
systems and metering pump systems have proven suitable and have received 
extensive use.
    (C) Mixing chambers shall be used between the diluter and the test 
chamber(s). This may be a small container or flow-splitting chamber to 
promote mixing of test substance stock solution and dilution water, and 
is positioned between the diluter and the test chambers for each 
concentration. If a proportional diluter is used, separate delivery 
tubes shall run from the flow-splitting chamber to each replicate test 
chamber. Daily checks on this latter system shall be made.
    (D) Silverside fry are injured easily and are susceptible to 
impingement on the mesh of the incubation cups. Consequently, water flow 
into and out of the cups when counting fry must be at a slow rate. This 
can be accomplished by using small diameter (e.g., 2 mm I.D.) capillary 
tubes to drain the test solution from spitter boxes into the replicate 
test chambers. The use of a self-starting siphon to gradually lower 
(i.e., less than or equal to 1 min.) the water level approximately 2 cm 
in the test chamber is recommended. A minimum water depth of 5 cm should 
be maintained in the cups. Although it may be satisfactory, a rocker-arm 
type apparatus has not yet been used with silversides.

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    (v) Other equipment required. (A) An apparatus for removing 
undesirable organisms, particulate matter and air bubbles.
    (B) An apparatus for aerating water.
    (C) A suitable magnifying viewer for examination of minnow embryos.
    (D) A suitable apparatus for the precise measurement of growth of 
the fish, including both length (e.g., with metric or ruler caliper or 
photographic equipment) and weight.
    (E) Facilities for providing a continuous supply of live brine 
shrimp nauplii (Artemia salina).
    (F) For silversides, facilities for providing a supply of rotifers 
(Brachionus plicatilis) for approximately 11 days.
    (G) Facilities (or access to facilities) for performing the required 
water chemistry analyses.
    (vi) Cleaning of equipment. (A) Test substance delivery systems and 
test chambers should be cleaned before use. Test chambers should be 
cleaned during the test as needed to maintain the dissolved oxygen 
concentration, and to prevent clogging of the embryo cup screens and 
narrow flow passages.
    (B) Debris can be removed with a rubber bulb and large pipette or by 
siphoning with a glass tube attached to a flexible hose. Debris should 
be run into a bucket light enough to observe that no live fish are 
accidentally discarded.
    (vii) Dilution water--(A) General. (1) A constant supply of 
acceptable dilution water should be available for use throughout the 
test. Dilution water shall be of a minimum quality such that the test 
species selected will survive in it for the duration of testing without 
showing signs of stress (e.g., loss of pigmentation, disorientation, 
poor response to external stimuli, excessive mucous secretion, lethargy, 
lack of feeding, or other unusual behavior). A better criterion for an 
acceptable dilution water for tests on early life stages should be such 
that the species selected for testing will survive, grow, and reproduce 
satisfactorily in it.
    (2) The concentration of dissolved oxygen in the dilution water 
(fresh or salt) shall be between 90 percent and 100 percent saturation. 
When necessary, dilution water should be aerated by means of airstones, 
surface aerators, or screen tubes before the introduction of the test 
substance.
    (3) Water that is contaminated with undesirable microoganisms (e.g., 
fish pathogens) shall not be used. If such contamination is suspected, 
the water should be passed through a properly maintained ultraviolet 
sterilizer equip ped with an intensity meter before use. Efficacy of the 
sterilizer can be determined by using standard plate count methods.
    (B) Freshwater. (1) Natural water (clean surface or ground water) is 
preferred, however, dechlorinated tap water may be used as a last 
resort. Reconstituted freshwater is not recommended as a practical 
dilution water for the early life stage toxicity test because of the 
large volume of water required.
    (2) Particulate and dissolved substance concentrations should be 
measured at least twice a year and should meet the following 
specifications:

------------------------------------------------------------------------
                Substance                      Concentration maximum
------------------------------------------------------------------------
Particulate matter.......................  <20 mg/liter.
Total organic carbon (TOC)...............  <2 mg/liter.
Chemical oxygen demand (COD).............  <5 mg/liter.
Un-ionized ammonia.......................  <1 [mu]g/liter.
Residual chlorine........................  <1 [mu]g/liter.
Total organoposphorus pesticides.........  <50 ng/liter.
Total organochlorine pesticides plus       <50 ng/liter.
 polychlorinated biphenyls (PCBs).
Total organic chlorine...................  <25 ng/liter.
------------------------------------------------------------------------

    (3) During any one month, freshwater dilution water should not vary 
more than 10 percent from the respective monthly averages of hardness, 
alkalinity and specific conductance; the monthly pH range should be less 
than 0.4 pH units.
    (C) Saltwater. (1) Marine dilution water is considered to be of 
constant quality if the minimum salinity is greater than 150/
00 and the weekly range of the salinity is less than 
150/00. The monthly range of pH shall be less than 
0.8 pH units. Saltwater shall be filtered to remove larval predators. A 
pore size of [lE]20 micrometers (um) is recommended. For silversides, 
the recommended salinity is 20 ppt and shall be maintained between 15 
and 25 ppt throughout testing.
    (2) Artificial sea salts may be added to natural seawater during 
periods of

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low salinity to maintain salinity above 150/00.
    (3) Test parameters--(i) Dissolved oxygen concentration. It is 
recommended that the dissolved oxygen concentration be maintained 
between 90 and 100 percent saturation; but it shall be no less than 75 
percent saturation at all times for both minnow species and between 90 
and 100 percent saturation for the trout species in all test chambers. 
Dilution water in the head box may be aerated, but the test solution 
itself shall not be aerated.
    (ii) Loading and flow rate. (A) The loading in test chambers should 
not exceed 0.1 grams of fish per liter of test solution passing through 
the test chamber in 24 hours. The flow rate to each chamber should be a 
minimum of 6 tank volumes per 24 hours. During a test, the flow rates 
should not vary more than 10 percent from any one test chamber to any 
other.
    (B) A lower loading or higher flow rate or both shall be used if 
necessary to meet the following three criteria at all times during the 
test in each chamber containing live test organisms:
    (1) The concentration of dissolved oxygen shall not fall below 75 
percent saturation for the fathead and sheepshead minnows and 90 percent 
for the rainbow and brook trout;
    (2) The concentration of un-ionized ammonia should not exceed 1 [mu] 
g/1; and
    (3) The concentration of toxicant should not be lowered (i.e., 
caused by uptake by the test organisms and/or materials on the sides and 
bottoms of the chambers) more than 20 percent of the mean measured 
concentration.
    (iii) Temperature. (A) The recommended test temperatures are:
    (1) Fathead minnow----25 [deg]C for all life stages.
    (2) Sheepshead minnow----30 [deg]C for all life stages.
    (3) Rainbow and brook trout----10 [deg]C for embryos. 12 [deg]C for 
fry and alevins.
    (4) Atlantic and tidewater silversides----25 [deg]C for all life 
stages.
    (B) Excursions from the test temperature shall be no greater than 
2.0[deg]C. It is recommended that the test system 
be equipped with an automatic alarm system to alert staff of 
instantaneous temperature changes in excess of 2 [deg]C. If the water is 
heated (i.e., for minnow species), precautions should be taken to ensure 
that supersaturation of dissolved gases is avoided. Temperatures shall 
be recorded in all test chambers at the beginning of the test and weekly 
thereafter. The temperature shall be recorded at least hourly in one 
test chamber throughout the test.
    (iv) Light. (A) Brook and rainbow trout embryos shall be maintained 
in darkness or very low light intensity through one week post-hatch, at 
which time a 14-hour light and 10-hour dark photoperiod shall be 
provided.
    (B) For fathead and sheepshead minnows, a 16-hour light and 8-hour 
dark (or 12:12) photoperiod shall be used throughout the test period.
    (C) For silversides, a 14-hour light and 10-hour dark photoperiod 
shall be used throughout the test period.
    (D) A 15-minute to 30-minute transition period between light and 
dark is optional.
    (E) Light intensities ranging from 30 to 100 lumens at the water 
surface shall be provided; the intensity selected should be duplicated 
as closely as possible for all test chambers.
    (e) Reporting. A report of the results of an early life stage 
toxicity test shall include the following:
    (1) Name of test, sponsor, investigator, laboratory, and dates of 
test duration.
    (2) Detailed description of the test substance including its source, 
lot number, composition (identity and concentration of major ingredients 
and major impurities), known physical and chemical properties, and any 
carriers (solvents) or other additives used.
    (3) The source of the dilution water, its chemical characteristics, 
and a description of any pretreatment.
    (4) Detailed information about the test organisms including 
scientific name and how verified and source history, observed diseases, 
treatments, acclimation procedure, and concentration of any contaminants 
and the method of measurement.
    (5) A description of the experimental design and the test chambers, 
the depth and volume of the solution in the chambers, the way the test 
was begun, the number of organisms per treatment, the number of 
replicates, the

[[Page 132]]

loading, the lighting, a description of the test substance delivery 
system, and the flow rate as volume additions per 24 hours.
    (6) Detailed information on feeding of fish during the toxicity 
test, including type of food used, its source, feeding frequency and 
results of analysis (i.e., concentrations) for contaminants.
    (7) Number of embryos hatched, number of healthy embryos, time to 
hatch, mortality of embryos and fry, measurements of growth (weight and 
length), incidence of pathological or histological effects and 
observations of other effects or clinical signs, number of healthy fish 
at end of test.
    (8) Number of organisms that died or showed an effect in the control 
and the results of analysis for concentration(s) of any contaminant in 
the control(s) should mortality occur.
    (9) Methods used for, and the results of (with standard deviation), 
all chemical analyses of water quality and test substance concentration, 
including validation studies and reagent blanks; the average and range 
of the test temperature(s).
    (10) Anything unusual about the test, any deviation from these 
procedures, and any other relevant information.
    (11) A description of any abnormal effects and the number of fish 
which were affected during each period between observations in each 
chamber, and the average concentration of test substance in each test 
chamber.
    (12) Reference to the raw data location.

[50 FR 39321, Sept. 27, 1985, as amended at 52 FR 19064, May 20, 1987]