&EPA
United States
Environmental Protection
Agency
Office of Chemical Safety
and Pollution Prevention
(7101)
EPA712-C-016
January 2012
        Ecological Effects
        Test Guidelines
        OCSPP 850.3100:
        Earthworm Subchronic
        Toxicity Test

-------
                                     NOTICE

     This guideline is one of a series of test guidelines established by the United States
Environmental Protection Agency's Office of Chemical Safety and Pollution Prevention
(OCSPP) for use in testing pesticides and chemical substances to develop data for
submission to the Agency under the Toxic Substances Control Act (TSCA) (15 U.S.C. 2601,
et seq.), the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) (7 U.S.C. 136, et
seq.), and section 408 of the Federal Food, Drug and Cosmetic (FFDCA) (21 U.S.C. 346a).
Prior to April 22, 2010, OCSPP was known as the Office of Prevention, Pesticides and Toxic
Substances (OPPTS). To distinguish these guidelines from guidelines issued by other
organizations, the numbering convention adopted in 1994 specifically included OPPTS as
part of the guideline's  number.  Any test guidelines developed after April 22, 2010 will use
the new acronym (OCSPP)  in their title.

     The OCSPP harmonized test guidelines serve as a compendium of accepted scientific
methodologies and protocols that are intended to provide data to inform regulatory decisions
under TSCA, FIFRA, and/or FFDCA. This document provides guidance for conducting the
test, and is also  used  by EPA, the public, and the companies that are subject to data
submission requirements under TSCA, FIFRA, and/or the FFDCA.  As a guidance
document, these guidelines are not binding on either EPA or any outside parties, and the
EPA may depart from  the guidelines where circumstances warrant and without prior notice.
At places in this  guidance, the Agency uses the word "should."  In this guidance, the use of
"should" with regard to an action means that the action is recommended rather than
mandatory. The procedures contained in this guideline are strongly recommended for
generating the data that are the subject of the guideline, but EPA recognizes that departures
may be appropriate in specific situations. You may propose alternatives to the
recommendations described in these guidelines, and the Agency will assess them for
appropriateness on a  case-by-case basis.

     For additional information about these test guidelines and to access these guidelines
electronically, please go to http://www.epa.gov/ocspp and select "Test Methods &
Guidelines" on the left side navigation menu.  You may also access the guidelines in
http://www.requlations.qov grouped by Series under Docket ID #s: EPA-HQ-OPPT-2009-
0150 through EPA-HQ-OPPT-2009-0159, and EPA-HQ-OPPT-2009-0576.
                                   Page i of 17

-------
OCSPP 850.3100: Earthworm subchronic toxicity test.

(a) Scope—
       (1) Applicability. This guideline is intended to be used to help develop data to submit to
       EPA under the Toxic Substances Control Act (TSCA) (15 U.S.C. 2601, et seq.),  the
       Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) (7 U.S.C. 136, et seq.), and
       the Federal Food, Drug, and Cosmetic Act (FFDCA) (21 U.S.C. 346a).
       (2) Background.  The source materials used in developing this harmonized OCSPP test
       guideline include the OPPT guideline under 40 CFR 795.150 Earthworm Toxicity Test
       (proposed in the Federal Register of June 25, 1991 (56 FR 29155)) and ASTM E  1676,
       Standard Guide for Conducting Laboratory Soil Toxicity or Bioaccumulation Tests with
       the  Lumbricid Earthworm Eisenia fetida.  This guideline was  formerly Public  Draft
       OCSPP 850.6200 (April, 1996).

(b) Purpose. This guideline is intended for use in developing data on the toxicity of chemical
substances  and mixtures ("test chemicals" or "test substances") subject to environmental effects
test regulations.   This guideline sets forth the procedures for a toxicity test using earthworms
which are maintained in direct contact with an artificial (formulated) soil, allowing earthworms
to ingest contaminated soil ad libitum.  The Environmental Protection Agency will use data from
this test in assessing the hazard of a chemical to earthworms in the soil environment.

(c) Definitions.  The definitions in OCSPP 850.3000 apply to this guideline.  In addition,  the
more specific definitions in this paragraph also apply to this guideline:

       Artificial (formulated) soil means a defined dry weight mixture of 70 percent (70%) of
       number 70 mesh silica  sand, 20% kaolin clay, 10% sphagnum peat moss, and calcium
       carbonate (to adjust the pH).  These ingredients are weighed and mixed in the  stated
       proportions and moistened to 35-45% (by weight) with reagent water.

       Behavioral symptoms are indicators of  toxicity  to earthworms such  that  a  distinct
       difference in position in the test container can be identified, e.g., below surface or on the
       surface; writhing on the surface; stiffened and shortened on the surface or elongated and
       pulsing;  or inactive below surface in a ball.

       Clitellum means a glandular portion of the anterior epidermis, appearing as saddle-shaped
       or annular, usually  differentiated externally by color.  It is  the most visible feature  of an
       adult earthworm and secretes the cocoon into which eggs and sperm are deposited.

       Mature or adult worms mean a condition of the worm  exhibiting  a  clitellum in  the
       anterior of the body.

       Mortality means the  lack of movement by the test organism in response to  a definite
       tactile stimulus to the anterior end. Also, because earthworms tend to disintegrate rapidly
       after death, the absence of organisms in the enclosed soil test container is considered to
       mean death has occurred.

       Pathological symptoms mean toxic effects, such as surface lesions and mid-segmental
       swellings or general ulcerated areas on the surface of the earthworm.

                                      Page 1 of 17

-------
       Test mixture means the test substance/artificial soil mixture(s) which the earthworms are
       exposed to during the test.

(d) General considerations—

       (1)  Summary  of the test.   This toxicity test is  conducted by placing acclimated
       earthworms in test chambers containing artificial (formulated) soil which has been spiked
       with the test substance.   Earthworms are allowed to ingest this  test mixture soil ad
       libitum.  Mortality and other effects are examined on a weekly basis for 28 days.  The
       results are expressed as the 28-d LCso (median lethal concentration).   Sublethal effects
       may also be determined, and expressed as ECso, (experimentally derived concentration of
       a test  substance in a test matrix (e.g., growth medium, soil sediment, feed) that would be
       expected to  cause a defined adverse  effect in 50%  of  a group  test organisms under
       specified exposure conditions), NOEC (no observed effect concentration), LOEC (lowest
       observed effect concentration), and MATC (maximum acceptable toxicant concentration)
       values.

       (2)  General test  guidance.  The general  guidance in OCSPP 850.3000 applies to this
       guideline except as specifically noted herein.

       (3)  Range-finding test.  A range-finding  test  is usually  conducted  to establish the
       appropriate test concentrations to be used in the definitive test.  The earthworms should
       be exposed (for at least 28 days) to a  series of widely spaced concentrations of the test
       substance (e.g., 0.1,  1.0,  10, 100, 1,000 milligrams per kilogram (mg/kg) dry weight
       artificial  soil).  Treatment replication  is not needed  and  nominal concentrations of the
       chemical are acceptable.  The number  of test organisms used and details of observations
       do not have to be the same as definitive testing. However, the range-finding test will be
       more  useful  the greater the  similarity  between the range-finding test and the definitive
       test.  Results of  range-finding tests should be reported along with the results of the
       definitive test, if range-finding tests are conducted.

       (4)  Definitive test.  The  goal of the  definitive test  is to determine the concentration-
       response curve  for mortality and the LCso (95% confidence limits and standard error) at
       28 days, as well as the slope of the concentration-response curve, its associated standard
       error and 95% confidence interval.  Where sufficient data warrant,  these values are also
       calculated for the 7, 14, and 21-day  concentration response-curves for mortality.  An
       additional desired endpoint is the weight loss ECso  (95% confidence interval) and the
       LOEC, NOEC  and MATC values  at each sampling time.  For this  determination,  a
       minimum of five concentrations of the  test chemical, plus appropriate controls, are tested.
       Analytical confirmation  of test concentrations is performed  as  described in  OCSPP
       850.3000. A summary of test conditions is provided in Table 1 and validity elements for
       an acceptable definitive test are listed in Table 2 of this guideline.

       (5)  Limit test.  In some situations, it is only necessary to ascertain that the 28-d LCso is
       above a certain limit, and at the  limit there is also no observable adverse growth effect.
       In a limit test, at least 20 earthworms are exposed to a single "limit concentration," with
       the  same number of organisms  in  appropriate control(s).  The multiple-concentration
       definitive test may be waived if the following  conditions  are met.   First, if one or fewer
       mortalities occur  at the limit concentration (i.e.  the  LCso > limit concentration), and
                                      Page 2 of 17

-------
       second,  the  limit treatment responses  are  not significantly reduced  (or inhibited) as
       compared to the control response  (i.e.,  NOEC  > limit  concentration).   For  most
       chemicals, 1,000 mg test substance (based upon 100% active ingredient for pesticides)
       per kg dry weight of artificial soil is considered appropriate as the limit concentration.
       Except for the number of treatment groups and number of test organisms, an acceptable
       limit test follows the same test procedures and is the same duration as the definitive test
       (see Table 1  of this guideline).

(e) Test standards—

       (1) Test substance.  The substance to be tested should be technical grade unless the test
       is designed to test a specific formulation, mixture, or end-use product.  For pesticides, if
       more than one active ingredient constitutes a technical product, the technical grade of
       each active  ingredient  should be tested separately, in addition to the combination,  if
       applicable.   OCSPP 850.3000 lists the type of information that should be known about
       the test substance before testing, and discusses methods for preparation of test substances.

       (2) Test duration.  The test duration is 28 days.

       (3) Test organism—

             (i) Species.  The test  species is the earthworm Eisenia fetida andrei (Bouche).
             Some taxonomists consider these  to be two  separate  species, Eisenia fetida
             (Savigny  1826)  and Eisenia andrei  (Andre 1963); see  the  references under
             paragraph (j)(l), (J)(5) and (j)(H) of this  guideline for additional  information
             about the taxonomy of the Eisenia fetida complex.   These organisms naturally
             inhabit high  organic environments such as compost and manure piles.  They are
             easily bred  in  the  laboratory and  have  been used  commonly  in laboratory
             experiments.  The species identity of the test organism should  be verified using
             appropriate  taxonomic keys as described by Fender (paragraph  (j)(4)  of this
             guideline), or an equivalent method.

             (ii) Source.

                    (A)  Earthworms used in  toxicity  tests  should be  purchased  from  a
                    commercial source that can verify the  species.   Once verified, cultures
                    should be maintained at the  test facility.   Information about culturing
                    procedures can be  found  in  the reference  in  paragraph  (j)0)  °f this
                    guideline. Records should be kept regarding the source of the  initial stock
                    and culturing techniques.  All organisms used for a particular test should
                    have originated from the same population (culture).

                    (B) All newly acquired earthworms  should be quarantined and observed
                    for at least 14 days prior to use in a test.

             (iii) Age and size. Adult earthworms are used to start the test.  The weight of the
             individual adult earthworms should be between 300 mg and 600 mg each.  All
             organisms used in a test should be as uniform as possible in the state of maturity
             and weight.
                                       Page 3 of 17

-------
       (iv) Acclimation.  It is recommended that earthworms be  cultured at the test
       temperature. In any event, earthworms should be held for a minimum of 7 days in
       uncontaminated soil at the test temperature prior to testing. Any changes in soil
       temperature should not exceed 3 degrees Celsius (°C) per day or 1 °C per hour.

       (v) Health status.  Earthworms should not be used if they have been under stress
       from too much moisture or a lack of moisture as  described  by Reinecke and
       Venter (see paragraph (j)(13) of this guideline); excessive  or inadequate food or
       temperature as described  by Tomlin and Miller  (paragraph  (j)(17) of this
       guideline); pH variation as described by Satchell and Dottie (paragraph (j)(14) of
       this guideline); or crowding.  Any of these conditions  will produce earthworms
       that may not be healthy.

       (vi) Care  and handling.   Adult  earthworms  should be handled with care.
       Sufficient numbers of earthworms should be harvested and sorted to insure that
       healthy individuals are used for the test. For a satisfactory test, any  animals that
       appear to  be injured are discarded and not used  in the test.   Additionally, any
       organisms that touch dry surfaces or are dropped  or injured during handling are
       discarded.

       (vii) Diet and feeding—

              (A) Culture Period.  Substrate food for culturing Eisenia fetida andrei
              should  be commercial  alfalfa (Medicago  saliva) pellets, saturated with
              reagent water at a ratio of approximately 1 gram (g)  of dry pellets per 2
              milliliters (mL) water and aged for two weeks in a covered container.
              Worms are fed once or twice per week and the bedding  turned by hand to
              inspect the general condition of the culture.

              (B) Test Period. The earthworms are not fed during the  test period.

(4) Administration  of test substance.  The  test is  started  by introducing adult
earthworms, which have been acclimated to the test conditions, into test chambers which
contain artificial (formulated) soil  (see paragraph (e)(7)(vii) of this guideline)  to which
the test substance has been added.  Earthworms should be  introduced into test soils on the
surface of the test medium so as  to evaluate burrowing  behavior. The jar capped and
secured without making an airtight seal.

       (i) Preparation of treated soil.

              (A) Appropriate portions  of artificial soil  are mixed thoroughly with
              appropriate  amounts of test substance (see paragraph (e)(4)(i)(B) of this
              guideline).  Hand  mixing or mechanical mixing  may be  used.  Test
              concentrations should be prepared  on day -1 and  allowed to equilibrate
              overnight before adding test organisms.

              (B) Test substances may be  added directly to the artificial soil  on a dry
              weight  basis, but are typically dissolved in  reagent water (preferably) or a
              vehicle to form  a stock  solution.  Aliquots of the stock  solution,  or
                               Page 4  of 17

-------
              dilutions thereof, are then added to the artificial soil.  If a solvent is used,
              the opened chambers are placed in a hood for 24 hours to evaporate the
              solvent prior to adding the earthworms.

       (ii)  Test  concentrations.    For the  definitive  test,  a  minimum  of  five
       concentrations of the test chemical, plus appropriate  controls,  are tested.  Test
       concentrations should be chosen in a geometric  series in which  the ratio is
       between 1.5  and 2.0 (e.g., 2, 4, 8, 16, 32,  and 64 mg/kg).  All test concentrations
       should be based  on milligram  of test chemical  (100% active ingredient for
       pesticides) per kilogram of artificial soil (air-dry weight).

(5) Controls

       (i) Every test should include  a negative control consisting of the same artificial
       (formulated) soil,  conditions, procedures, and earthworms from the same group as
       used with the test substance, except that none of the test substance is added.  In
       addition if a vehicle is used,  a vehicle control is tested,  using the same vehicle
       batch  as used to make the stock solution and at the highest concentration used to
       prepare test concentrations.  See OCSPP  850.3000 for additional information on
       preparation of test substances using a vehicle.

       (ii) A test is not acceptable if average survival of either  the negative  or solvent
       control earthworms was less  than 80% at the  end of the test or the total mean
       weight of the earthworms  in  either the  negative or  solvent control containers
       declined significantly during the test (i.e., by 30%).

(6) Number of test organisms and replicates—

       (i) Definitive test.  In the definitive test, there is a minimum of three replicates for
       each  treatment  concentration  and control group, with  a minimum  of  10
       earthworms per replicate. The earthworms are selected from the culture randomly
       into groups of 10.  These groups are then  randomly assigned to the test chambers
       and then weighed to  verify  they do  not differ more than ±  10%  among the
       replicates.  Each test chamber contains 200 g (dry weight) of artificial soil. Each
       test chamber should contain an equal amount of test soil and an equal number of
       earthworms.   For a satisfactory test, replicate test chambers are to be physically
       separated,  since  the test chamber is  the experimental  unit.   In addition,  test
       chambers within the testing area are positioned in a random manner or in a way in
       which appropriate statistical analyses can be used to determine the variation due
       to placement.

       (ii) Limit  test. In  a limit  test, at least 20 earthworms  are exposed to a single
       "limit  concentration,"  with  the  same  number  of  organisms in  appropriate
       control(s).

       (iii) Loading.  The number of earthworms placed in a test chamber should not be
       so great as to affect the results of the test.
                                Page 5 of 17

-------
(7) Facilities, apparatus and supplies.  Normal laboratory equipment and supplies, and
items especially listed in (e)(7)(i) through (e)(7)(vii).

       (i) Facilities.

              (A) Facilities should be well ventilated and free of fumes and disturbances
              that may affect the test organisms.

              (B) Ventilation hood for evaporating solvent from test soil when a solvent
              is used.

       (ii) Instruments and general equipment.

              (A) Suitable balances to measure soil mixtures.

              (B) A properly calibrated balance with sufficient accuracy should be used
              to weigh the worms.

       (iii) Culturing. Polyethylene  containers (e.g., rectangular dish pans measuring
       32.5 by 27.5 by 12.5 centimeters) for culturing earthworms.

       (iv) Environmental control equipment.

              (A) Apparatus for providing continuous lighting.

              (B) A mechanism (e.g.,  environmental chamber) for controlling  and
              maintaining the artificial soil temperature and relative humidity during the
              culturing, holding, acclimation, and test periods.  Relative humidity should
              be maintained  above 85%. An open pan of water can be used for this
              purpose to prevent moisture loss from the containers.

       (v) Test containers and exposure system.

              (A) Chambers  for exposing test earthworms to the test substance.  Glass
              canning jars, 1-pint  capacity, or their  equivalent, should  be  used for
              testing.  The lids should be reversed (i.e.,  turned upside down), loosely
              capped and secured without making an airtight seal to reduce evaporation
              and permit air exchange.

              (B) Construction materials  and  equipment that contact test  mixtures
              should not contain substances that  can be leached  or dissolved  into
              artificial soil in  quantities that can affect the test  results.   Construction
              materials and equipment that contact test mixtures should  be chosen to
              minimize sorption of test substances.

       (vi) Cleaning.  The test chambers should be cleaned before each test following
       standard  laboratory procedures.   Hard glass jars  are preferable and should be
       heated in an  ashing oven between tests. For a satisfactory test, if soft glass is used
       it should be used only once and then be discarded.  Refer to OCSPP  850.3000 for
       additional information.
                               Page 6 of 17

-------
       (vii) Artificial soil.

              (A) For each  test substance concentration  and control tested, enough
              artificial soil is prepared by recipe to yield  270 g of artificial  soil (wet
              weight) per replicate.  The constituents identified in  this paragraph are
              mixed together on a dry weight basis: 10% Canadian sphagnum peat moss
              (that portion passing through a 2.36 millimeter (mm) screen); 20% kaolin
              clay (97% kaolinite with a particle size under 40 micrometers (|im)); and
              70% silica sand (grade 70, 97.1% particle size of 0.053 to 0.3 mm).

              (B) After  these  materials are  mixed  together,  an amount of calcium
              carbonate (99% purity) is added to the mixture to adjust the soil pH to 6.5
              ±0.5.  The amount of calcium  carbonate used will  depend on the  pH of
              the peat moss used.

              (C) An appropriate amount of reagent water (e.g., 70 g per 200 g of dry
              soil) is added to the artificial soil and mixed with the artificial soil to raise
              the artificial soil moisture level to 35% by weight.

(8) Environmental conditions.  Environmental parameters during the test should  be
maintained as follows:

       (i) Temperature.  The  test  soil temperature should be 22 °C and it should  be
       constant within ±  2 °C during the test, as described by Edwards (paragraph (j)(3)
       of this guideline),  or using an equivalent method.

       (ii)  Lighting and photoperiod.  Replicates should  be illuminated continuously
       with incandescent or fluorescent lights as described by Edwards (paragraph (j)(3)
       of this guideline),  or using an equivalent method. Light intensity should be about
       5.7  micromoles per square meter per second (|imol/m2/s) (for cool-white lights,
       this is equivalent to approximately 420 lux) measured at the artificial soil surface.

(9) Observations. Earthworms in the test chambers are observed periodically during the
test; the dead worms are  removed and the findings recorded. Soil temperature and pH,
and  the concentration of test substance in  the  treated soil are measured at  specified
intervals.   Data collected during the test are used to develop  concentration-response
curves and  LCso values for the test substance.

       (i)  Measurement  of  test substance.   Analytical  confirmation   of test
       concentrations in artificial soil  is to  be performed using validated  analytical
       methods, as described in OCSPP 850.3000.  A 10-g sample should be removed
       from each replicate prior to addition  of earthworms  to measure pH and test
       substance  concentrations.  The homogeneity of the test substance in treated soil
       should be determined.

              (A) For stable test substances, monitor test concentrations at the beginning
              and at  the end of the test.  However,  for volatile,  unstable substances,
              those subject to  ready degradation,  or  where there  is uncertainty in the

                                Page 7 of 17

-------
       analytical   measurements,  it  may  be   necessary   to  measure  test
       concentrations more often during the test, e.g. every seven days.

       (B) In addition to analyzing samples of artificial soil, at least one reagent
       blank, containing all reagents used, should  also be analyzed.

       (C) The measured concentration of the test substance  in artificial soil in
       any chamber during the test should not  vary more than 50% from the
       measured  concentration prior to initiation of the test;  concentration
       measurements should be as described  by Neuhauser  et al.  (paragraphs
       (j)(9) and (j)(10) of this guideline), or an equivalent method.

       (D) The mean measured concentration  of test substance in artificial soil
       (dry weight) should be used to plot all concentration-response curves and
       to calculate all LCso, ECso, LOEC, and NOEC values.

(ii) Environmental conditions—

       (A) Temperature.  Temperature should be measured and reported at the
       beginning of the test and on days  7, 14, 21, and 28 in all test chambers.
       The temperature should be measured at least hourly in one test container.

       (B) Light intensity.  Light intensity should be measured at least once
       during the test at the surface of the container and checked weekly in the
       test chambers.

       (C)  Total  organic  carbon  (TOC)  concentration.    The  TOC
       concentration in soil at test initiation should be determined as measured by
       the method of Plumb (paragraph (j)(12) of this guideline), or an equivalent
       method.

       (D) Soil pH.  The  pH should be measured at test initiation and 7 day
       intervals (days 7, 14, 21, 28) thereafter in each test chamber.

(iii) Organisms—

       (A) Mortality,  behavior, and other adverse effects.   At test initiation
       burrowing  behavior  of earthworms placed on the surface  of the test
       medium is recorded for each test chamber.  Each test and control chamber
       should  be  checked  for  dead or affected  earthworms  and  observations
       recorded 7, 14, 21, and 28 days after the beginning of the test or within 1
       hour  of the designated times in all test chambers.  Missing  earthworms
       should be considered to have died. Mortality is assessed by emptying the
       test medium on  a glass or other inert surface, sorting earthworms from the
       test mixture and testing their reaction  to a gentle  mechanical stimulus.
       Any adverse effects (e.g., behavioral or pathological symptoms) are noted
       and should be reported. The medium is returned to each container.
                         Page 8 of 17

-------
                    (B) Weight loss.   Total biomass of test organisms per test chamber is
                    measured at the beginning and  end of the test.  The worms should be
                    washed and purged before weighing.  To accomplish this, the bedding is
                    rinsed from the worms with reagent water; the worms are placed in petri
                    dishes with wet filter paper, and allowed to purge the gut contents for 24
                    hours. Before weighing worms,  excess surface water may be removed by
                    placing the worms between layers of an absorbent towel. However, it is
                    very important not to dry the surface of the worms which might stress the
                    worms unduly.

(f) Treatment of results—

       (1) Descriptive summary statistics—

             (i) Environmental conditions.  The soil characteristics and TOC content should
             be described.  Temperature and light intensity results should be summarized in
             tabular form, showing the range, mean and  standard deviation during the test.
             The pH in each test chamber should  be  summarized in tabular form, showing the
             range, mean, and standard deviation.

             (ii)  Test  substance  soil  concentration.   Soil  concentrations  should  be
             summarized in tabular  form by treatment  and sample time, showing mean
             concentrations and standard deviations.  The treatment mean soil concentration
             should be calculated.

             (iii) Mortality.  Death is the primary effect used in this test guideline to evaluate
             the toxicity of  the test substance.   The number of initial earthworms  at each
             treatment and control and the number of dead earthworms should be summarized
             in tabular form by observation time (e.g. day 7, 14, 21,  and  28) treatment, and
             replicate.

             (iv) Sublethal effects  and growth.  The sublethal effects and growth (i.e., fresh
             weight) data should be used to determine concentration-response curves, calculate
             ECso values, and  determine LOEC, NOEC,  and  MATC values.   Number  of
             earthworms with  abnormal  appearance  or behavior  symptoms  should  be
             summarized in  tabular form by  symptom, time of observation, treatment, and
             replicate.   Mean total biomass at the  beginning and  end of the  test for each
             treatment replicate  should  be  summarized in tabular  form and the mean and
             standard deviation in weight loss or gain calculated by treatment.

       (2) Percent—

             (i) Mortality.  Calculate the percent mortality at each treatment level and control
             by observation time.

             (ii) Appearance and behavior.  Calculate  the percent effected at each treatment
             level and control by symptom, and observation time.
                                     Page 9 of 17

-------
(3) Limit test—

       (i)  LCso value.  At test termination (28 days), if one or fewer earthworms are
       dead at the limit concentration, the LCso is considered to be greater than the limit
       concentration.  This is because the Binomial  Theorem predicts that when 20
       earthworms are tested, the probability of seeing <1 dead earthworm if the true 28-
       d LCso  is  at  or below  the  limit  concentration  is  <0.001.   Conversely  the
       probability of seeing 2  or more dead earthworms  if the true 28-d LCso is at or
       below the limit dose is  >0.999.  Therefore, if <1 mortality  occurs among the 20
       earthworms  tested, the  28-d  LCso  is  reported  as  greater than  the limit
       concentration (i.e., 28-d LCso >1,000 mg/kg dry wt in soil).

       (ii) Proportion of mortality (p ). The Binomial Theorem also can provide both
       an  estimate of the true  proportion of mortality ( p ) in the population as well as
       confidence bounds on that estimate (see Table A4 of the reference in paragraph
       (j)(2)).  For small sample sizes the interval may be large. For no mortalities in 20
       earthworms (p = 0), the upper 99% confidence bound on  the estimate of p is
       0.24 (95% upper confidence bound is  0.17),  this means that the estimate of the
       true proportion of mortality may actually be as high as 0.24 when no earthworms
       die out of 20 tested (or as high as 0.17 for the 95% confidence estimate). For  one
       mortality in 20 earthworms  (p = 0.05), the upper 99% confidence bound on the
       estimate of p is 0.32 (95% upper confidence bound is 0.29). For assessing risks,
       the  confidence in the proportion  impacted is considered in determining acute
       effects at environmental exposure doses.

       (iii) NOEC. To ascertain that there is no observable adverse growth effect at the
       limit treatment (i.e., NOEC  >  limit dose), the  limit treatment  response is
       compared  to the  control treatment response  using  a one-sided  two-sample
       parametric or nonparametric test for a  reduction in growth from the control (see
       OCSPP 850.3000).  The minimum significant difference detectable by the test or
       a similar estimate of the sensitivity of the test should be determined and reported.

       (iv) Multiple-concentration definitive testing.

             (A) At  test termination, if two or more mortalities occur among  the 20
             earthworms tested or growth was significantly reduced from the control, a
             definitive dose-response test should be conducted.

             (B) Multiple-concentration definitive testing  may be  waived  if  at  test
             termination (28  days), one or  fewer earthworms  are  dead  at the limit
             concentration, and at  the  limit treatment there  is also  no observable
             adverse growth effect.

(4) Multiple-concentration definitive test—

       (i)  Concentration-response curve,  slope and LCso.  Statistical procedures are
       employed to calculate the 28-d LCso (standard error and 95% confidence interval)
       based upon mortality.  If a concentration-response  model (e.g., probit) was fit to
                               Page 10 of 17

-------
              the  data to determine  the LCso,  the  model parameters (e.g., slope) and their
              uncertainty estimates (e.g., standard error) should be recorded.

              (ii) Concentration-response curve, slope and ECso.  Statistical procedures are
              employed to calculate the 28-d ECso (standard error and 95% confidence interval)
              based upon biomass weight loss.  If a concentration-response model was fit to the
              data  to determine  the ECso, the  model  parameters (e.g.,  slope)  and their
              uncertainty estimates (e.g., standard error) should be recorded.

              (iii) NOEL.  Appropriate statistical methods (e.g.,  one-way analysis of variance
              and multiple comparison tests) should be used to test  for significant  differences
              between treatment means and determine LOEC, NOEC and MATC for mortality,
              biomass weight loss, and other sublethal effects.

              (iv)  Statistical methods.   Statistical  procedures for  modeling quantal  and
              continuous data are available and should be used.   Additional discussion about
              measurement endpoints and statistical procedures is found in OCSPP 850.3000.

(g) Tabular summary of test conditions.  Table 1  lists the important conditions that  should
prevail during the definitive test.   Except for the number of test  organisms per concentration,
number of replicate chambers, and test concentrations, Table 1 also lists the important conditions
that should prevail  during a limit test.  Meeting these  test conditions will greatly increase the
likelihood that the completed test will be acceptable or valid.
                                      Page 11 of 17

-------
       Table 1.—Summary of Test Conditions for Earthworm Subchronic Toxicity Test
Test type
Test duration
Temperature
Light quality
Light intensity
Photoperiod
Test chamber size
Substrate
Substrate amount per replicate
Age/size of test organisms per replicate
Number of test organisms per concentration
Number of organisms per test chamber
Number of replicate chambers per concentration
Loading
Feeding regime
Test concentrations
Measures of Effect or Measurement Endpoints
Spiked formulated soil
28 days
22 °C (constant during test within ± 2 °C)
Incandescent or fluorescent lights
5.7 umol/m2/s (approximately 420 lux)
Continuous light
Glass canning jars, 1 pint, or equivalent
Artificial (formulated) soil
270 g wet weight (200 g dry weight)
Adult earthworms, 300 - 600 mg
30 (minimum)
10
3 (minimum)
300 - 600 mg per 270 g of soil
No feeding during test
Minimum of 5 test concentrations chosen in a
geometric series plus a control, and a vehicle
control if a vehicle is used
LC50 based upon mortality at 28 days at a minimum;
EC50, NOEC, LOEC and MATC based upon
sublethal effects (weight change)
(h) Test validity elements.  This test would be considered to be unacceptable or invalid if one or
more of the conditions in Table 2 occurred. This list should not be misconstrued as limiting the
reason(s) that a test could be found unacceptable or invalid.  However, except for the conditions
listed in Table 2 and in OCSPP 850.3000, it is unlikely a study will be rejected when there are
slight variations  from guideline environmental conditions and study design unless the  control
organisms are significantly  affected, the precision of the test is reduced,  the power of a test to
detect differences is reduced, and/or significant biases are introduced in defining the magnitude
of effect on measurement  endpoints as compared to guideline conditions.  Before departing
significantly from this guideline, the investigator should contact the Agency to discuss the reason
for the departure and the effect the change(s) will have on test acceptability.  In the test report, all
departures from  the guideline  should be identified, reasons for these changes given, and  any
resulting effects on test endpoints noted and discussed.
                                      Page 12 of 17

-------
       Table 2.—Test Validity Elements for Earthworm Subchronic Toxicity Test
1. All test chambers were not identical.

2.  Treatments  were  not randomly  assigned to individual test  chamber locations or individual test
organisms were not impartially or randomly assigned to test chambers.

3. The negative and vehicle control [when a vehicle was used] were not included in the test.

4. Average survival of either the negative or solvent control earthworms was less than 80% at the end of
the test.

5. The total mean weight of the earthworms in the control containers declined  significantly during the test
(i.e., by 30%).
(i) Reporting—

       (1)  Background information.  Background information to be supplied in the report
       consists at a minimum of those background information items listed in paragraph (j)0) of
       OCSPP 850.3000.

       (2)  Guideline deviations.  Provide a statement of the guideline or protocol followed.
       Include a description of any deviations from the test guideline or any occurrences which
       may have influenced the results of the test.

       (3) Test substance.

              (i) Identification of the test substance:  common name, IUPAC and CAS names,
              CAS number, structural formula,  source, lot or batch number, chemical state or
              form of the test substance, and its purity (i.e. for pesticides,  the identity and
              concentration of active ingredient(s)).  If radiolabeled substance was used provide
              the radio purity  and location(s) of the label.

              (ii) Storage conditions of the test chemical or test substance and  stability of the
              test chemical or test substance under storage conditions if stored prior to use.

              (iii) Methods used for preparation of artificial soil, its age (i.e., prepared  1 day or
              7 days prior to use), and storage conditions if stored prior to use.  If artificial soil
              is not used describe the source, collection method, handling and preparation of
              soil used in the test, its composition  (percent sand,  silt,  and clay), and textural
              classification.

              (iv) Source and amount of hydration water added to test soil and the moisture
              content for the test mixture at test initiation.

              (v) Methods of  preparation of the  test substance and the treatment concentrations
              used in  the range-finding and definitive  test,  or limit test:  description of test
              chemical introduction  into the test medium (e.g., as a powder, stock solution), the
              mass and volume of  soil  and test substance used for  each treatment, how test
                                      Page 13 of 17

-------
       substance was mixed into  the soil, number  of treatments  and nominal test
       substance concentration in soil in each treatment at the beginning of the test.

       (vi) If a vehicle (e.g., solvent) is used to prepare stock or test substance provide:
       the name and source  of the  vehicle, the  nominal concentration(s) of the test
       substance in  the  vehicle, in  stock solutions,  or  mixtures, and the  vehicle
       concentrations used in the treatments.

       (vii) Description of stock solution preparation.

(4) Test organisms.

       (i) Scientific and common names and method of verification, and source.

       (ii) Culture method and conditions, and feeding history.

       (iii) Health status of culture used for collection of test earthworms (e.g., any
       prophylactic or preventative treatments, quarantine period).

       (iv) Collection method and date of collection.

       (v) Acclimation period.

       (vi) Age and weight (by treatment and replicate) in tabular form at test initiation.

(5) Test system and conditions.  Description of the test system and conditions used in
the definitive or limit test, any preliminary range-finding tests, and any positive control
tests.

       (i) Description of the test chambers: type, size, volume, material, and conditioning
       method.

       (ii) Statement verifying that earthworms were not fed during the test.

       (iii) Volume and weight of soil used in each test container.

       (iv) Time between introduction and mixing of the test substance with the soil and
       introduction of the earthworms.

       (v) Number of worms per test container.

       (vi) Number of test containers per concentration.

       (vii) Methods used for test container and treatment randomization as well  as
       methods for impartial assignment of earthworms to test containers.

       (viii) Method of introducing earthworms to test containers.

       (ix) Test duration.


                               Page 14 of 17

-------
       (x) Methods and frequency of environmental  monitoring performed during the
       definitive or limit study for lighting, soil temperature and soil pH.

       (xi) Method, type and frequency of observations made on earthworms during the
       test.

       (xii) For the definitive or limit test, all  analytical  procedures and  preservation
       methods should  be described.  The  accuracy  of the method,  method detection
       limit, and limit of quantification should be given.
(6) Results.
       (i) Environmental monitoring data results (lighting, soil temperature and pH) in
       tabular form  (provide  raw data for measurements not made on  a continuous
       basis), and descriptive statistics (mean, standard deviation, minimum, maximum).

       (ii) For preliminary range-finding test(s), if conducted, the number of dead  and
       intoxicated earthworms at each concentration level and in the control(s).

       (iii) For the definitive and limit test, test substance concentration in the soil at test
       initiation (day 0), during (if needed, at day 7, 14, 21) and test conclusion (day 28),
       in tabular form  and  descriptive  statistics (time weighted  average, standard
       deviation, minimum, maximum).

       (iv) The total  organic carbon (TOC) content  of the soil mixture.

       (v) For the definitive  and  limit test, the number of dead earthworms  at each
       observation period at each treatment level and control(s) (provide the raw data).

       (vi) For  the  definitive  and  limit test, the burrowing  behavior of earthworms
       observed at test initiation: description of behavior, duration, severity, and number
       affected at each treatment level and control(s) (provide the raw data).

       (vii) For the definitive and limit test, a description of all observations made on the
       test earthworms that are suggestive  or predictive of toxicity and all concomitant
       gross toxicological manifestations include time of onset, duration, severity,  and
       number affected at each treatment level and control(s) (provide the raw data).

       (viii) For the definitive and limit test,  the  weight, in tabular form, at each  test
       concentration (including controls),  in  each test chamber at test initiation  and
       termination.

       (ix) For  the  definitive  test, the LCso  value,  and its  standard error and 95%
       confidence interval  should be reported for  7, 14, 21, and 28-day periods.  The
       slope of the concentration-response curve, its standard error, and 95% confidence
       interval should also be reported.

       (x) For the definitive test, the ECso for weight with its standard error and 95%
       confidence interval,  and the LOEC, NOEC, and MATC for day 28.

                               Page  15 of 17

-------
             (xi) Description  of statistical  method  used,  including software package,  for
             determining LCso ECso, LOEC, NOEC, and MATC values and the concentration-
             response model parameters and the basis  for the choice of method.  Provide
             results of any  goodness-of-fit  tests and determination of minimum significant
             differences.

(j) References.  For additional background information on this test guideline, the references in
this paragraph should be consulted:

       (1) American Society for Testing and Materials. ASTM E 1676-04, Standard guide for
       conducting laboratory soil  toxicity  or  bioaccumulation  tests with  the  lumbricid
       earthworm Eisenia fetida  and the enchytraeid potworm Enchytraeus albidus. Current
       edition approved April 1, 2004. In Annual Book of ASTM Standards, Vol.  11.06, West
       Conshohocken, PA.

       (2)  Conover, W.  1980.  Practical Nonparametric Statistics, 2nd Edition. John Wiley &
       Sons, Inc., New York, NY.  493 pp.

       (3) Edwards, C.A., 1984. Report of the second stage  in development of a standardized
       laboratory method for  assessing the toxicity of chemical substances to earthworms. The
       Artificial Soil Test. DG Xl/AL/82/43, Revision 4.

       (4) Fender, W.M., 1985.  Earthworms of the Western United States. Part 1. Lumbricidae,
       Megadrilogica 4: 93-129.

       (5) Jaenicke, J., 1982.  "Eiseniafoetida" is two biological species. Megadrilogica 4:6-8.

       (6)  Greene,  J.C.,  Bartels,  C.L.,  Warren-Hicks, W.J.,  Parkhurst,  B.R., Linder,  G.L.,
       Peterson, S.A., and Miller,  W.E.,  1989. Protocols for  Short-Term Toxicity Screening of
       Hazardous Waste  Sites, EPA/600/3-88/029, U.S.  Environmental Protection Agency,
       Environmental Research Laboratory, Corvallis, OR.

       (7) Hartenstein, R. et a/., 1979. Reproductive potential of the earthworm Eisenia foetida.
       Oecologia ¥3:329-340.

       (8) Meier, J.R., Chang, L.W., Jacobs,  S.,  Torsella,  J., Meckes, M.C. and Smith, M.K.,
       1997.  Use of plant and earthworm bioassays to evaluate remediation of soil from a site
       contaminated with polychlorinated biphenyls. Environmental Toxicology and Chemistry
       16(5): 928-938.

       (9) Neuhauser, E.F. et a/., 1986.  Contact and  artificial soil tests using earthworms to
       evaluate the impact of wastes in soils, In:  Hazardous and Industrial Soil Waste Testing:
       Fourth_Symposium, ASTM STP 886. J.K. Petros, Jr. and R.A. Conway, eds.,  American
       Society for Testing and Materials. Philadelphia, PA pp. 192-203.

       (10) Neuhauser, E.F.  et a/.,  1985.  The toxicity of selected organic chemicals  to  the
       earthworm Eisenia fetida. Journal of Environmental Quality 14: 383-388.
                                     Page 16 of 17

-------
(11) Oien,  N. and J.  Stenerson, 1984.  Esterases of earthworm  - III. Electrophoresis
reveals that Eisenia foetida (Savigny) is two species.   Comparative Biochemistry and
Physiology 78c (2):277-282.

(12) Plumb, R.H., Jr.,  1981.  Procedures for handling and chemical analysis of sediment
and  water samples.   Technical  Report  EPA/CE-81-1,  prepared  by  Great  Lakes
Laboratory,  State  University  College  at Buffalo,   Buffalo,  NY.,  for  the  U.S.
Environmental Protection Agency/Corps of Engineers Technical Committee on Criteria
for Dredged and Fill Material. U.S. Army Engineer Waterways Experiment Station, CE,
Vicksburg, MS.

(13) Reinecke,  AJ.  and Venter, J.M.,  1987.   Moisture  preferences,  growth  and
reproduction of the compost worm Eisenia fetida (Oligochaeta).  Biology and Fertility of
Soils 3: 135-141.

(14) Satchell, I.E. and Dottie, D.J., 1984. Factors affecting the longevity of earthworms
stored in peat. Journal of Applied Ecology 21: 285-291.

(15) Stafford, E.A.  and Edwards, C.A., 1985. Comparison of heavy metal  uptake by
Eisenia faetida  with  that of  other  common  earthworms.  Final  Technical Report.
Entomology Department,  Rothamsted Experiment Station, Harpenden, Herts. ALS 2JQ,
U.K. U.S. Army Contract DATA 45-84-0027.

(16) Spurgeon, DJ. andHopkin, S.P., 1995. Extrapolation of the laboratory-based OECD
earthworm toxicity test to metal-contaminated field sites. Ecotoxicology 4:190-205.

(17) Tomlin, A.D. and Miller,  J.J., 1980. Development and fecundity of the manure
worm, Eisenia faetida (Annelida:Lumbricidae),  under  laboratory  conditions.  In: D.L.
Dindal (ed.), Soil Biology as Related to Land Use Practices. Proc. 7th Internal. Soil Zool.
Coll. of ISSS. EPA, Washington, DC., pp. 673-678.

(18) vanGestel, C.A.M., and van Dis, W.A., 1988. The influence of soil characteristics on
the earthworm Eisenia fetida andrei (Oligochaeta). Biology and Fertility of Soils 6:262-
265.
                               Page 17 of 17

-------