United States
          Environmental Protection
          Agency
Environmental Research
Laboratory
Gulf Breeze FL 32561
          Research and Development
EPA/600/8-87/043 March 1988
&EPA   Methods for Toxicity
          Tests of Single
          Substances and Liquid
          Complex Wastes with
          Marine Unicellular
          Algae

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          Errata Sheet for EPA/600/8-87/043

  Methods for Tox/c/ty Tests of Single Substances and
 Liquid Complex Wastes with Marine Unicellular Algae


Please note that Figure 3 (p. 28) and Figure 6 (p. 41) are transposed. The
figure captions are correct.

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                              EPA/600/8-87/043
                                 March 1988
Methods for Toxicity Tests of Single
  Substances and Liquid Complex
Wastes with Marine Unicellular Algae
              Gerald E.Walsh
   ENVIRONMENTAL RESEARCH LABORATORY
  OFFICE OF ENVIRONMENTAL PROCESSES AND
                EFFECTS
   OFFICE OF RESEARCH AND DEVELOPMENT
   U. S. ENVIRONMENTAL PROTECTION AGENCY
       GULF BREEZE, FLORIDA 32561
                 \5PL-I6]
                 ir^et, HOOP

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                           Disclaimer


    This document has been reviewed in accordance with U.S. Environmental
Protection  Agency policy and  approved  for publication. Mention  of trade
names or commercial  products  does  not constitute endorsement  or
recommendation for use.

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                        Table of Contents
Abstract	   v
Acknowledgments   	   vi
1  Principles of Aquatic Toxicity Testing with Algae 	   1
   1.1   Introduction  	   1
   12   Growth Curve of Unicellular Algae in Culture   	   1
   1.3   Factors That Influence Growth of Unicellular Algae in Culture   3
   1.4   Maintenance of Algal Cultures  	   7
   1 5   Choice of Species	      	   7
   1.6   Measurement of Population Density  	   8
   1.7   Living and Dead Cells	   9
   1 8   Numerical Expression of Effect 	   9
   1.9   Addition of Toxicant   	   10
   1.10  Bioaccumulation  	   10
   1.11  Summary   	   10
   1 12  References	   11
2. Toxicity Tests With  Marine Unicellular Algae  	   16
   2.1   Introduction	   16
   2.2   Definitions of Terms   	   16
   2 3   Personnel     	   17
   2.4   Safety 	   17
   2.5   Disposal of Toxicants  	   18
   2.6   Quality Control  	   18
   2.7   Chemical and Physical Properties of Test Substances  ....   18
   2.8   Chemical Analyses of Test Substances  	   19
   2.9   Equipment  	   19
   2.10  Test Species	   21
   2.11  Axenic Culture  	     	   21
   2.12  Growth Medium  	   22
   2.13  Medium for Use in Studies on Toxicity of Heavy Metals   ..   23
   2.14  Medium for Use with Tests on Liquid Complex Mixtures   ..   25
   2.15  Fractionation Procedure for Liquid Complex Wastes    ....   29
   2.16  Test for Living  and Dead Cells  	   29
   217  Bioaccumulation	   29
   218  Documentation and Reporting of Results    	   29
   2.19  References   	    29
3. Growth Test with Single Substances  	   31
   3.1   Preparation of Toxicant	   31
   3 2   Toxicant Concentrations  	   31
   3.3   Test Procedure  	   32
4. Growth Tests with Liquid Complex Wastes  	   38
   4.1   Collection  of Waste	   38

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   4.2   Filtering of Waste  	       	   38
   4.3   Sterile Techniques	      38
   4.4   Estimation of Population Density   ...       	38
   4.5   Calculation of Effect Concentration	    40
   4.6   Procedure for Effects of Whole Waste   ...        	   42
        4.6.1  Preparation of Medium      ...          	      42
        4.6.2  Procedural Steps  . .           ...       	      42
   4.7   Procedures for Effects of Inorganic and Organic Fractions   .   44
        4 7 1  Preparation and Testing of Inorganic and  Organic
              Fractions	      	   44
        4.7 2  Procedural Steps   .         	      46
   4.8   Procedures for Effects of Inorganic and Organic Subfractions  49
        4.8.1  Inorganic Subfractions   .     	   49
              4 8.1.1 Preparation and Testing of the Cation
                    Subfraction  .      	   50
              4812 Preparation and Testing of the Anion
                    Subfraction              	   51
        4.8.2  Organic Subfractions       	   53
              4 8 2.1 Preparation and Testing of the Subfractions      53
   4.9   Procedure for Extraction and  Testing of Particles  	    55
        4.9 1  Extraction of Organics   	     	   55
        4.9 2  Testing of Extract   	   55
   4.10  References	       	   55
5.   Bioaccumulation Test  	   60
6.  Enumeration of Living and Dead Cells   ....        	   63
   6.1   References  	   64

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                               Abstract


    This manual describes methods for laboratory toxicity testing with marine
unicellular algae. It consists of six parts: Part I describes principles of aquatic
toxicity  testing  with algae  It describes algal growth curves and factors that
influence algal  growth  including light,  temperature,  composition of culture
medium, and pH.  Methods  for maintenance  of algal  cultures,  choice  of
species for testing, estimation  of population density, detection  of living and
dead cells, expression of toxicant effect, and bioaccumulation are discussed.
    Part II defines terms related to algal toxicity testing, describes equipment
needed for algal toxicity tests, and gives detailed methods for preparation of
algal growth medium  and estimation of population density by cell counts and
spectroscopy.
    Part III describes the recommended toxicity  test with single substances.
The test is conducted for 48 h,  at which time population densities of control
and treated cultures are measured and the median  effect concentration and
growth rates are calculated
    Part IV gives methods  for estimating effects of liquid complex wastes on
growth  of algae  Methods are  described  for  analysis  of  whole waste, its
organic  and inorganic fractions,  anion,  cation,  base neutral, and  acid
subtractions,  and particulars matter
    Part V describes a  method for estimation of bioaccumulation of single
substances by algae in culture.
    Part VI gives a method for distinguishing living and dead algal cells
    Each of the above tests addresses a different aspect of hazard evaluation
of single substances or  mixed waste with regard to inhibition or stimulation of
algal population growth,  survival, and possible introduction of toxic substances
into food chains. When  population growth tests are combined with studies on
bioaccumulation and algicidal  or algistatic  properties of  a  toxicant,  an
overview of important effects is obtained, and several relevant effects criteria
provide  a  base  for regulation of   single  substances and   mixtures  of
substances.

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                      Acknowledgments

    Sincere thanks are given to the following who reviewed  the  entire
manuscript of this  manual  and  offered  valuable  suggestions  for  its
improvement: Dr. Dennis Ades, Department of Environmental Quality, State of
Oregon, Portland, Oregon;  Dr.  John H.  Duffus,  Heriot-Watt University,
Edinburgh, Scotland;  Mr.  Terrence  A. Hollister, EPA,  Region VI, Houston,
Texas; Dr. Niels  Nyholm, Water Quality  Institute, Horsholm, Denmark;  Dr.
Ronald L. Rashke, EPA, Region IV, Athens, Georgia; and Dr. Jerry Smrchek,
EPA, Office of Toxic Substances, Washington, D.C.
    Thanks also are given to Mrs. Val Coseo, who had the onerous task of
typing several drafts of the manual and did so in a professional and cheerful
manner, and to reviewers at the Environmental Research  Laboratory, Gulf
Breeze: Dr. Thomas W. Duke, Dr. David A. Flemer, Mr. Larry Goodman,  Mr.
Jack I. Lowe, Dr. Foster L.  Mayer, Mr. P.R. Parrish, and Mr. Marlin E. Tagatz.
                                  VI

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  1.  Principles of Aquatic Toxicity Testing with Algae

1.1 Introduction

This manual describes methods for use of marine unicellular algae in toxicity
tests. Although no common method has been used by testing laboratories,
those described here have  been used successfully in  tests with pesticides,
heavy metals, other toxic substances,  and  complex  industrial  wastes.
Methods have differed  mainly  in composition of  algal  growth  medium, test
species, and endpoint, each of which may affect expression of toxicity.  The
methods described here recommend a carefully formulated growth medium,
sensitive algal species, and three means for  estimation  of algal population
density.
    Toxicity testing with unicellular algae requires application of the principles
of phycology and microbiology  to culturing, handling,  and  exposing  the
organisms.   Success in culturing and  testing  depends upon the knowledge
and competence of  the responsible person  The technician who works with
unicellular  algae must be  familiar   with  methods  for maintenance  of
nonbacterized cultures and their transfer to fresh media, identification of algal
species  and deviations from  normal  morphology, rates  of growth  of algal
species  in  culture,  use of laboratory  instruments, such as   microscopes,
counting  chambers,  analytical  balances,   light  and  fluorescence
spectrophotometers, and all other aspects of  culture and testing  described
below

1.2 Growth Curve of Unicellular Algae in Culture

Algal  population  growth  in  culture follows  a  predictable  course under
controlled conditions of light, temperature, and nutrient concentration  After
inoculation of growth medium with a known number of cells of a standard age,
the usual pattern of population  growth  includes a lag phase,  phase  of
exponential growth,  phase  of  declining growth  rate, stationary phase, and
death phase (Fig.  1). See Kaufmann (1981) for a discussion of  use of growth
curves   The period of time  for  each phase under  optimal  conditions is
specific  for each  algal species.   It is not  necessary  to use synchronous
cultures in toxicity tests because the exponential growth phase, in  which  cell
number  increases at a high rate, is required
    The  pattern  of  population growth is  very important in toxicity  testing
because toxicants and growth  stimulating  substances cause deviations from
normal  (Fig.  2).   Generally,  two responses  of  algal  populations to test
substances are measured:  (1)  Rate of growth over  part   or all  of  the
exponential phase is determined and growth of treated  cultures is  compared
with growth of control cultures.   Population  density or  a   mathematical

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Logarithm of Population Density




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expression of the growth rates of control and exposed cultures at a selected
time may be compared  (2) Final population density is an important criterion
for detection of growth-inhibiting and growth-stimulating substances and  for
characterizing eutrophic natural waters.
    Length  of  the  lag  phase may  be critical  to  success because  it  can
determine duration of the  toxicity test.  To minimize the length of the  lag
phase, cultures must be initiated with the proper number of cells from algal
stocks in the early exponential phase. Use of older cells may cause a lengthy
lag phase.
    Duration of the toxicity test is  very important.  Algal  tests should  be
conducted within as  short  a time period as possible to minimize problems
with fate of the test chemical in the exposure flasks. When the solution, with
algae,  is placed under lighting required for algal growth, concentration  of the
chemical may  decline due  to photodegradation,  molecular  instability,
adsorption  to vessel walls, volatilization from  the surface  of the  medium,
adsorption to algal cells, absorption by algal cells, or biodegradation.  Shape
of the growth curve in response to a  chemical may be due, at least in part, to
behavior of that chemical in the  test system For example,  loss of  chemical
over a selected period of time could  determine the rate of decrease in growth
or period of increased lag phase.
    Because of the confounding factor of chemical  fate, it may be difficult to
interpret algal toxicity data  from static tests.  Walsh (1983) demonstrated that
the IC50  (interpolated  concentration of a   toxicant that would inhibit  algal
population growth by 50%)  increased  with time of exposure.  Thus, it is
recommended that  test duration  be no longer than  three days, at which time
population densities (which are  low) and growth rates (which are high) of
control and exposed populations may be compared by either graphical inter-
polation from density data or by comparison  of the growth rates.
    If the final  yield of algae is required for growth stimulation studies, the
test must be continued until the early stationary phase.

1.3 Factors that Influence Growth of Unicellular Algae in Culture

There  are  five major factors that  affect growth of  algae  in culture: light
(quality, intensity, duration), temperature, and composition, salinity, and pH of
the growth medium.  Each must be controlled carefully, with little deviation
among tests.
    LIGHT  Algae are cultured under artificial illumination in  the laboratory,
but such  illumination  may differ  greatly from  natural sunlight in quality
(spectral composition),  intensity,  and duration    These  three  characteristics
may be regulated for optimal growth of individual species   When species with
different optimal requirements are held  in a single  growth chamber, average
conditions that support growth can be maintained.
    Intensity  of light has a  strong influence on growth and  physiological state
of algal populations (Beardall and Morns, 1976,  Hitchcock, 1980; Perry  et al.,
1981; Cosper,  1982; Soeder  and  Stengel, 1974;  Gallagher  et al.,  1984;
Falkowski et  al.,  1985).  Gallagher et al. (1984) reviewed  a  portion of the
literature on effects of light intensity on rates of  growth and photosynthesis,
pigments, the photosynthetic unit, and means of photoadaptation of algae.  In

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addition,  light intensity may  influence release of products of photosynthesis
from algal  cells (Fogg,  1965;  Fogg  et  al.,  1965;  Hellebust,  1965,  1967;
Nalewajko,  1966;  Watt,  1966,  1969;  Bellin and Ronayne,  1968),  thus
increasing the amount of dissolved organic matter in  growth  medium and,
perhaps,  affecting uptake of the test substance
    Light intensity may also affect behavior of the test chemical.  Rates of
photodecomposition of numerous compounds are related to intensity of light
and, when photodecomposition is rapid,  it may be  the major factor that
determines toxicity. Kamp-Neilsen (1969) reported that toxicity of copper to
Chlorella pyrenoidosa was related to light intensity.
    Care must be taken to insure little variation in illumination of algal cultures
because light  intensity  can  influence growth  rate  and  physiological
characteristics of algal populations and behavior  of test chemicals.  Intensity
of light in growth chambers must be kept constant for all tests and should not
exceed the  optimal for algal population  growth.  Light intensity should  be
recorded daily, and when it falls  to 90% of optimal,  the lamps should  be
replaced.
    Spectral composition of  light can  affect growth and photosynthetic  rates
and cellular morphology of  algae  (Humphrey,  1983).   As for  other
photosynthesizing  plants,  energy of visible light  in the wavelength range of
400 to 729  nm  is incorporated by pigments specialized for  absorption of
electromagnetic  radiation. The  various algal   divisions contain  different
amounts  of the three types of pigments that absorb light: (1) chlorophylls that
absorb blue and red light, (2) carotenoids that absorb  blue and  green  light,
and (3)  phycobilins that absorb green, yellow,  and orange light.  Tungsten
lamps emit light in wavelengths used by algae, but also emit a large amount
of heat that is  difficult to control in growth chambers. Fluorescent lights also
emit wavelengths that can be utilized  by algae,  and "cool white" fluorescent
tubes are used commonly, sometimes in conjunction with tungsten lamps.
    Spectral signatures of tungsten  and fluorescent lamps can usually  be
obtained from manufacturers.  Whatever the form of lighting,  it is essential
that lamps be replaced before gross changes  occur  in spectral signature.
Replacement when intensity diminishes is probably adequate  for consistent
spectral  output,  but changes in color of  light can sometimes be detected
visually.  If a color  change is seen, the lamp should be replaced.
    Marine unicellular algae may  be cultivated and tested under continuous
light or under  dark-light cycles.  Humphrey  (1979) described photosynthetic
characteristics of  algae  grown  under both  types of regimes'  algae grown
under a  12 h light - 12 h dark cycle had a higher photosynthetic rate and a
higher photosynthesis respiration  ratio, but a lower growth rate than those
grown under continuous lighting  These findings are important  to culture and
testing of algae.  All stock algal cultures and all tests  should be maintained
under the same lighting  conditions  to  insure comparability of  results.  In
addition, although temperature change  has little effect on photochemical
processes, optimal temperature for  population  growth  may vary  with light
intensity: increase in temperature increases the point at which light  saturation
occurs (Soeder  and Stengel, 1974).  The test  recommended  here requires
continuous  lighting at constant temperature to  insure population densities
large enough to allow  statistical evaluation of toxicity data after two days.

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    TEMPERATURE  Each algal species has a specific culture temperature
for  optimal growth  at a given  light intensity   Soeder  and Stengel  (1974)
reviewed algal adaptation to and effects of temperature on population  growth
rate,  cell growth,  and metabolic processes   Algae adapt  quickly  to
temperature change. However,  if tests are to be done at a temperature other
than that at which  algal  stocks are maintained, then new  stocks  must be
prepared and adapted to the new temperature. \Temperature should not vary
by more than one degree C from the desired temperature.
    ALGAL GROWTH MEDIA   There  have been numerous reviews of algal
nutrition in  relation to composition of growth medium (Provasoli et al., 1957;
Krauss, 1958; Provasoli, 1958,  1966;  McLachlan,  1959,  1964;  Droop, 1961,
1969; Gerloff, 1963; Nicholas, 1963; Hunter and Provasoli, 1964; Kester et al.,
1967;  Venkataraman, 1969;  Prat  et al.,  1972; Healy,  1973;  Stein,  1973;
O'Kelley, 1974).  Droop (1969) gave 65 references to different growth media
for  marine algae.  The major thrust in  development  of marine algal medium
has been elucidation of nutritional requirements and amounts of nutrients and
their ratios  required for growth and normal cell morphology. Modern media
are composed either of natural or artificial seawater to  which nutrients  are
added   Nutrient additions include orthophosphate (PGV), nitrate  (NOa"),
potassium,  magnesium, calcium,  sulphur, boron,  cnelated  trace metals,
vitamins, and silica  (for diatoms and some chrysophytes and xanthophytes).
See Droop (1977) for a discussion of nutrition of phytoplankton.
    Media  made  from  seawater have  been  used extensively for culture of
unicellular algae.  Guillard and Ryther (1962) described a medium (Medium f)
made from natural  seawater that  has  proved to be excellent for culture of
many algal species.  Medium f  and its nutritional variations,  f-1  (Guillard and
Ryther, 1962) and f/2 (Stein 1973), are  still in use today.
    Although  natural seawater-based media are often  excellent for  culturing
algae,  diel  and seasonal variability in its composition may control  rate of
growth. Johnston (1962) demonstrated seasonal variability  of ocean surface
water to support growth of algae.  Media prepared from  surface water of the
Gulf of Mexico support growth of algae  in our laboratory between October and
April, but not between May and  September, even though  nutrient enrichments
are identical.  Unless a relatively unchanging source is available, toxicity tests
with medium  prepared from natural seawater may not yield  comparable data
if the seawater is collected at different times.
    Growth media prepared  from  pure chemicals and distilled or deionized
water have been described (Morel et  al., 1979; Harrison et al.,  1980).  See
Morel  et al.  (1979) for a discussion  of  requirements  for algal synthetic
medium. Such media  have  the advantage  of constant salt  and  nutrient
composition without possible variations that can occur  in natural water.  This
is  especially  important if  fluorescence intensity is  used for estimation  of
population density (Tunzi et al,  1974; Slovacek and  Hannon, 1977; Gilbert et
al.,  1986). Synthetic media are particularly  advantageous  for  toxicity tests
because there is  little batch-to-batch variation: the only  significant variables
are the toxicants and their concentrations. In our laboratory, the medium of
Morel  et al.  (1979) produced  good growth  with normal  cell morphology.
However,  medium  prepared  as  described by  Morel et al. (1979)  is
unacceptable in toxicity tests because  algae are very sensitive to the toxicant

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carrier, acetone.  We have modified nutrient concentrations slightly to make it
acceptable in toxicity tests.
    Algal  growth  medium can also  be prepared from commercial  sea salt
mixtures. Preparation of media from  commercial sea salts is rapid and easy,
and algae grow  well in them  when nutrients are added.  Although overall
composition  is  known,  there  may  be lot-to-lot variability, with  possible
inhomogeneity within lots of commercial  mixtures.   We have  compared
growth and responses to toxicants in media made from five commercial sea
salt mixtures and natural seawater (Walsh et al., in press). We have used one
product, Rila  Salts® (Rila Products, Teaneck,  NJ), with good results in many
tests.  Although salinity was the same and  only small differences were found
in nutrient concentrations,  differences in response to the same toxicant were
large.  Sensitivity to toxicants  was generally greater  in medium made from
Rila Salts than other commercial formulations  (Walsh et al., in press),  with
good growth and normal morphology in carrier controls.
    Algal  medium  must be sterilized before  use.  Although autoclaving has
been used by many investigators, it is not recommended because of possible
contamination of medium  from steam under pressure   It is recommended
that  basal medium  be pasteurized and  that  nutrients be sterilized  by
membrane filtration and added to basal medium immediately before the test.
    Responses of algae to acetone when the  medium of Morel et al  (1979) is
used  demonstrate that care must be taken  in  choosing an algal  medium;
although  good growth and  normal  morphology may be  obtained with a
medium,  that medium may be unsuitable for use in toxicity tests
    When liquid  complex wastes  are to be  tested, growth medium  is
prepared by addition of  salts and nutrients used in synthetic medium (Walsh
and Alexander, 1983; Walsh et al., 1980, 1982; Walsh and Garnas,  1983), and
synthetic medium is used as the untreated control.  Filtration should be done
only if algae are  present in the waste before testing  The medium cannot be
sterilized  because physical and chemical properties of the  waste  may be
altered.
    SALINITY   Salinity  of  growth  medium affects  growth and  primary
production of algal  populations (Braarud,  1951; Nakanishi and Monsi, 1965,
Vosjan and Siezen, 1968). Algal species may be stenohaline, oligohalme, or
euryhaline.  Euryhaline species  tolerate a wide salinity range  by  adjusting
concentrations of organic solutes in the cell (Hellebust, 1976a, 1976b; Ahmed
and Hellebust, 1985), and osmoregulation and osmoadaptation may  also rely
on  activity and  specificity of ionic  pumps  (Soeder  and  Stengel,  1974).
Osmotolerant marine algae require time to  adjust to hypertonic and hypotonic
stress (Gilmour et al., 1982, 1984), and it is important that algae be cultured in
the salinity  of the  toxicity test for  several  stock transfers before the test
begins.   Salinity  must not change when inoculum culture is added to test
medium.
    pH  Since growth media and natural seawater are generally around pH 8,
this should not present a problem in  culturmg marine algae, but pH should be
measured and recorded before each test.  Measurement of pH after a test is
of little value because algal activities may change it by as much  as one pH
unit even in the highly buffered medium. Flasks should be shaken gently and
continuously  to maintain gaseous equilibrium between growth  medium and

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air. This should insure sufficient carbon dioxide in the medium to maintain pH
at less than 8.5.
    Deviations from the normal  pH  can indicate  improper preparation  of
medium. We have used media between pH 7.6 and 8.2 with good growth and
normal morphology. It is best to use  a single medium that  is constant from
test to test to  avoid effects of pH  on toxicity of test substances.  However,
when  medium  is prepared from highly acidic  or basic liquid waste, rather than
from deionized water, pH is adjusted to approximately 8.

1.4 Maintenance  of Algal  Cultures

Stock algal cultures are maintained in the laboratory under conditions of light,
temperature, and growth medium  identical  to  those  of the toxicity test.
Inoculation of new medium is  done under aseptic conditions during the phase
of declining growth or no later than early in the stationary  phase to insure that
healthy cells are  transferred.   Microscopic examination of stocks should be
made for cellular morphology at each transfer  If abnormal cells are  seen,
transfers should  be made at  an earlier time  in the growth curve, the culture
may  be contaminated, or  the growth medium may  have  been prepared
incorrectly. Usually, abnormal cells are caused by excess of one or more of
the trace metal  nutrients    Stock  cultures  are  checked for  aerobic  and
anaerobic bacterial contamination at approximately monthly intervals, or more
frequently if contamination is suspected.
    Algal stocks for toxicity tests should be in the early exponential growth
phase to avoid transfer of extracellular algal products and because over 99%
of the cells  are living and healthy during this phase (Walsh and Alexander,
1980). The  stocks  should  be examined  for cellular morphology and only
normal  cells, as  found  during the exponential phase  of population  growth,
should be used.

1.5 Choice of Species

The major factor that determines quantitative expression of toxicity is  the
species  used  in  the  toxicity  test.   Some species are more  sensitive than
others to toxicants, but it is impossible to  predict which species, or clone of a
species, will be most sensitive or resistant to a particular  toxicant. Choice
should  be from  ecologically important  or  abundant, generally sensitive
species that can be  cultured in the  laboratory  and with population growth
rates  that allow estimation of  density within two or three  days of inoculation.
Bonin et al. (1986)  listed six  principal criteria for choice of  test species: (1)
wide  geographical  distribution, (2) well-known  nutrient  requirements,  (3)
good  taxonomical characterization  of the strains, (4)  small  genetic and
phenotypic variability, (5) high growth rate, and  (6) ease of  handling.  They
also presented an important critical review of algae commonly used in toxicity
tests.
    When possible, test species should occur naturally in the areas that may
be affected by the toxicant. For example, if a toxicant is a threat to an inshore
environment, a species  isolated from a nonpolluted inshore environment may
be used  for maximum  utility of the test (Murphy and Belastock,  1980).
Usually,  algal clones  must  be purchased from a  laboratory  that maintains a
culture collection.

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    It is usually impractical to maintain  more than one or two test species in
culture.  Walsh and Alexander (1980) recommended the diatom, Skeletonema
costatum, because  it meets most criteria listed above  and  is  generally
sensitive to pollutants.  However, estimation of cell numbers cannot be made
on an electronic  particle  counter because the  diatom forms long chains.
Bonin et al.  (1986) offered compelling arguments  for use of the  diatom,
Thalassiosira pseudonana, which occurs as a single cell.
    The diatom, Minutocellus polymorphus Hasle, von Stosch and Syvertsen,
is recommended here.  It is sensitive to most pollutants,  population density
can be estimated easily, and the period of exposure to toxicants is  only 48
hours. In addition, estuanne and oceanic clones are available for site-specific
studies.

1.6 Measurement of Population Density

There are three common methods  for estimation of  population density  of
marine algal cultures:  cell counts,  light spectroscopy,  and  fluorescence
spectroscopy.  Brezonik et al.  (1975)  reviewed  methods for  estimation  of
population  density of cultured  algae,  Rehnberg et al.  (1982)  reviewed
limitations of electronic particle  counting methods when used in algal tests.
Each  method estimates a different aspect of the population.  Cell counts give
the  number  of cells in a volume of medium, and when performed  under the
microscope, cell morphology can be examined. Light spectroscopy estimates
the  concentration  of suspended particles  (algae)  by absorption of light, and
fluorescence spectroscopy estimates the  amount of chlorophyll in  cells in
suspension   Cell counts and spectroscopy  do not  give information on cell
size, morphology, physiological state,  or if cells are living or dead.
    No single method for population analysis is completely  satisfactory.  For
example, a  toxicant may  cause a large  number of small  cells or  a small
number of large cells, relative to untreated control populations, with biomass
equal to  the control.  Such effects lead to false conclusions from all three
methods, unless results are also expressed as cell size, measured with a size
distribution meter on  an  electronic particle counter, or as  fluorescence  per
cell.   Even here, counts may be misleading because particle counters cannot
distinguish  living from dead cells.  Fluorescence results  may  be  deceiving
because  fluorescence yield is  a function of chlorophyll  concentration and
chloroplast shape  Toxicants may cause change in cell chlorophyll content
without causing change in cell  number, or they  may cause deformation of
thylakoids, thus affecting fluorescence yield.
    Despite problems associated with  estimation of population density, we
have found good correlation between  results from the three  methods and, on
a practical  basis, recommend  them  for  use  with  most toxicants.  The
researcher should be aware, however, that some toxicants,  notably heavy
metals,  cause conformational changes  in algal cells that  may  affect results,
and  that effects  cannot be reported simply  as mathematical expressions
(IC50, EC50, SC20;  see below) derived  from cell  counts  or spectroscopal
data.  Enumeration of  deformed cells may be vital for determination of effects
of some substances.

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1.7 Living and Dead Cells

It is  often desirable to identify the mechanism that inhibits algal population
growth.   Toxicants may kill cells (algicidal)  or  simply inhibit  the  rate of
reproduction (algistatic).  Presumably,  algicides would  have  greater effects
than  algistats on algae in natural waters  because algicides kill resident and
allochthonous  species and  reduce ability  of  populations to adapt  to the
pollution.
    Cnppen and Perrier (1974) described a method  for identification of  living
and dead cells by direct counts with the vital stain, neutral red, and the mortal
stain, Evans blue.  Reynolds et  al. (1978)  used the method to demonstrate
that  chlorine-produced  oxidants did not kill  algae,  and  Walsh  (1983)
described use of Evans blue in toxicity tests with pesticides.   In  the  method
of Walsh (1983), algae are grown in uncontaminated  medium for 48 h  and the
living and dead cells enumerated. The algae are then exposed to toxicant for
24 h, living and dead cells again enumerated, and  decrease in  growth rate
and  increase  in  number of dead cells  compared  to untreated  control
populations.   The method provides for rapid estimation of algistatic and
algiadal potentials of toxicants.

1.8 Numerical Expression of Effect

Bioactivity  of  compounds toward algae  is expressed  as  the  interpolated
concentration that  would  cause a specific effect in a specific  period of  time.
Thus, the  72-h IC50 is the calculated concentration  that would inhibit
population growth  or a physiological  process of treated cultures by  50% of
untreated  cultures in  72 h.   The IC50  is also called  the  EC50 (effective
concentration)  Similar expressions are used  when cell death  is observed
(lethal concentration,  LC) or when growth or a physiological  process is
stimulated (stimulatory concentration, SC).  Test durations have  ranged from
hours for physiological and  growth endpomts to weeks for growth endpoints,
and effects as percentages of untreated controls have been reported between
1 and 99.  Effect concentrations  are calculated from tests in  which response
to a graded series of toxicant concentrations is measured and percentage (of
untreated cultures) response is related to concentration.  Methods that  have
been  used for calculation of algal response include:  graphical  interpolation
(Yamane et al., 1984, APHA, 1985),  moving  average  interpolation  (Harris,
1959; Stephan, 1977), probit regression  (Finney, 1971; Ordog,  1981), and
binomial  (Harris,  1959)   Walsh  et al. (1987)  discussed these  methods as
applied  to  growth tests, compared  EC50s calculated  by them,  found  no
significant differences, and suggested use of graphical interpolation because
it is simple, rapid, and accurate.
    Two  other expressions  are   used  to  describe toxicity.  The  Lowest
Observed Effect  Concentration  (LOEC)  is the  lowest  concentration  of a
substance  in  a toxicity  test that has an  adverse  effect on the exposed
population  when  compared  to the untreated  control population.   The  No
Observed Effect Concentration (NOEC) is the highest concentration used in a
test that has no observed effect on the exposed population.

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1.9 Addition of Toxicant

In toxicity tests, a range of toxicant concentrations is used to encompass the
desired percentage response, e.g ,  if the IC50 is to be used for expression of
algal response, concentrations should include the NOEC, the 100% response
concentration, and concentrations that inhibit growth by more than and less
than 50%, such as 35 and 65%. At least five concentrations should be used
for establishment of the concentration-response curve.
    Most toxicants are poorly soluble in water and  must be dissolved in a
solvent carrier before addition to test medium.  Concentration  of solvent is
critical to success of a test.  It must be  as low as possible and  the same for
every toxicant concentration.  Carrier controls must be included  in every test,
with  algal growth equal to that of noncarrier controls.  We  have found
(unpublished data) that acetone  is  less toxic to marine algae than two other
frequently used carriers, tnethylene glycoi and dimethyl sulfoxide.  However,
acetone can affect results by interaction with toxicants, and the publications of
Stratton  (Stratton et al., 1980,  1982;  Stratton and Corke,  1981a,  1981b;
Stratton, 1986, 1987) should be consulted for review  of this subject.

1.10    Bioaccumulation

Although not necessarily related to toxicity, accumulation of toxicants  from
sublethal  concentrations in  water  may be  important to  toxicant fate and
transfer through  food chains.  Rice and Sikka (1973), Hollister et al. (1975)
and  Walsh  et al  (1977) showed  that living and  dead algal cells can
accumulate  toxicants   Banner  et  al.  (1977)  demonstrated transfer of the
pesticide, Kepone,  from contaminated  algae  to  oysters.  Bioaccumulation
studies are recommended for a more complete understanding of relationships
between algae and toxicants.

1.11     Summary

Algal toxicity tests include numerous microbiological procedures and culture
criteria that must be controlled carefully for accuracy and reproducibility.
There must be  test-to-test consistency in technique to insure comparable
data.  Algal  stock cultures must be maintained in a  healthy, growing  state.
Constant monitoring  of light intensity and temperature, care in preparation of
growth medium, analysis  of  growth  medium for  salinity and pH, and
morphological examination of  algal stock,  inoculum, and control  cultures
should insure healthy populations with reproducible growth  rates.   Algal
populations  used as inocula  for toxicity tests  must be taken from the  early
exponential  phase of growth  in  all tests.  By  carefully following established
good laboratory  practices for  culturing and testing, the trained technician can
generate data that describe  potential  effects of  chemical substances  on
population growth and survival and  on bioaccumulation by marine unicellular
algae.
                                   10

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1.12    References

Ahmed, I. and J.A. Hellebust. 1985. Salinity responses of the marine
    microalga Branchiomonas submarina Bohlin. J. Mar. Biol.  Ecol. 88:
    45-53.
APHA.  1985.  Standard Methods For the Examination of Water and Waste-
    water, 16th ed., American Public Health Association. Washington, DC.
Bahner, L.H., A.J. Wilson, Jr., J.M. Sheppard, J.M. Patrick, Jr., L.R. Goodman,
    and G.E. Walsh.  1977   Kepone® bioconcentration, accumulation, loss,
    and transfer through estuarine food chains.  Chesapeake  Sci.  18: 299-
    308.
Beardall, J. and I. Morris. 1976. The concept of light intensity in marine
    phytoplankton: some experiments with Phaeodactylum tncornutum. Mar.
    Biol. 37: 377-387.
Bellin, J.S. and M.E. Ronayne.  1968  Effects of photodynamic action on the
    cell membrane of Euglena  Physiol. Plant. 21. 1060-1066.
Bonin, D.J., M.R  Droop, S.Y. Maestrini, and M. C. Bonm. 1986.
    Physiological features of six micro-algae  to be used as  indicators  of
    seawater quality. Cryptogam Algol. 7:  23-83.
Braarud, T. 1951. Salinity as an ecological factor in marine phytoplankton
    Physiol. Plant 4: 28-34.
Brezonic, P.L., F.X. Browne, and J.L. Fox. 1975. Application of ATP  to
    plankton biomass and bioassay studies.  Water Res  9: 155-163.
Cosper, E.  1982. Effect of variations in light intensity on the efficiency of
    growth of Skeletonema costatum  (Bacillanophyceae) in  a  cyclostat   J.
    Phycol.  18:  360-368.
Crippen, R.W. and J.L  Perrier. 1974.  The use of neutral red  and Evans blue
    for live-dead determinations of marine plankton   Stain Technol. 49: 97-
    104.
Droop, M.R. 1961. Some chemical considerations in the design of synthetic
    culture media. Bot. Mar. 2: 231-246
Droop, M.R. 1969.  Algae, pp. 269-313,  in  Methods in Microbiology 3B
    (J.R. Norns and W  D. Ribbons, eds.), Academic Press, New  York.
Droop, M.R  1977. An  approach to quantitative nutrition of phytoplankton.
    J. Protozool.  24: 528-532
Falkowski, P G., Z Dubmsky, and K. Wyman.  1985.  Growth-irradiance
    relationships in phytoplankton.  Limnol.  Oceanogr. 30: 311-321.
Finney,  D.J. 1971. Probit Analysis, 3rd Ed., Cambridge University Press,
    New York.
Fogg, G.E.  1965. Algal Cultures and Phytoplankton Ecology.  University of
    Wisconsin Press, Madison.
Fogg, G.E., C. Nalewajko, and W.D. Watt.  1965. Extracellular products of
    phytoplankton photosynthesis.  Proc  R. Soc.  Lond. Ser  B 162" 517-
    534.
Gallagher, J.C , A.M. Wood, and R.S. Alberte  1984.  Ecotypic differentiation
    in the marine diatom Skeletonema costatum   influence of  light intensity
    on the  photosynthetic apparatus  Mar  Biol.  82  121-134.
Gerloff, G.C. 1963.  Comparative mineral nutrition of plants. Annu. Rev. Plant
    Physiol   14: 107-123.
                                  11

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Gilbert, P.M., T.M. Kana, R J. Olson, D LKirchman, and R.S. Alberte.  1986.
    Clonal comparisons of growth and photosynthetic responses to  nitrogen
    availability in marine Synechococcus spp.  J. Exp. Mar. Biol. Ecol 101:
    199-208.
Gilmour, D.J., M.F.  Hipkins, and A. D. Boney. 1982.  The effect of salt stress
    on the  primary  processes of photosynthesis in Dunaliella tertiolecta.
    Plant Sci  Lett. 26: 325-330
Gilmour, D.J., M.F.  Hipkins, and A.D. Boney.  1984.  The effect of decreasing
    the  external salinity on the  primary  processes  of  photosynthesis  in
    Dunaliella tertiolecta.  J. Exp. Bot. 150: 28-35.
Guillard, R.R L. and J H. Ryther. 1962.  Studies of marine planktonic diatoms.
    I  Cyclotella nana Hustedt,  and Detonula confervacea  (Cleve) Gran.  Can.
    J Microbiol  62: 229-239.
Harris, E.K   1959  Confidence limits for the LD50 using the moving average
    angle method   Biometrics 15: 424-432.
Harrison, P.J , R.E. Waters, and F.J R. Taylor. 1980.  A broad spectrum
    artificial  seawater medium for coastal and open ocean phytoplankton.  J.
    Phycol.  16:  28-35.
Healey, F.P   1973.  Inorganic nutrient uptake and deficiency in algae  Grit.
    Rev. Microbiol.  3:  69-113.
Hellebust, J.A. 1965. Excretion of some organic compounds by marine
    phytoplankton. Limnol Oceanogr  10:  192-206
Hellebust, J.A. 1967 Excretion of organic compounds by cultured and
    natural  populations of marine phytoplankton.  pp. 361-366, in Estuaries
    (G H. Lauff, ed.), American Association for the Advancement of  Science
    Publ. No. 83. Washington, DC.
Hellebust, J.A.  1976a.  Osmoregulation. Annu.  Rev  Plant Physiol. 27: 485-
    505.
Hellebust, J.A. 1976b.  Effect of salinity on photosynthesis and mannitol
    synthesis  in the green flagellate Platymonas suecica.  Can. J.  Bot. 54:
    1735-1741.
Hitchcock, G.L. 1980.  Influence of temperature on the growth rate of
    Skeletonema costatum in  response to  variations in  daily light intensity.
    Mar. Biol. 57: 261-269
Hollister, T.A., G.E. Walsh, and J. Forester   1975. Mirex and marine
    unicellualar algae: accumulation, population growth and oxygen evolution.
    Bull. Environ. Contam. Toxicol 14: 753-759.
Humphrey, G.F.  1979.  Photosynthetic characteristics of algae grown under
    constant illumination and light-dark regimes.  J.  Exp.  Mar. Biol. Ecol. 40:
    63-70.
Humphrey, G.F.  1983.  The effect of the spectral compositon of light on the
    growth,  pigments, and photosynthetic rate of unicellular marine algae.  J.
    Exp. Mar. Biol.  Ecol. 66: 49-67.
Hunter, S H. and L  Provasoli.  1964.  Nutrition of algae. Annu.  Rev. Plant
    Physiol  15: 37-56.
Johnston, R. 1962.  Seawater,  the natural medium of phytoplankton.  J  Mar.
    Biol. Assoc  U K. 43. 427-456.
Kamp-Neilsen, L. 1969.  The influence of  copper on the  photosynthesis and
    growth  of Chlorella pyrenoidosa.  Dans. Tidsskr. Farm. 43: 249-254.
                                   12

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 Kaufmann, K.W.  1981  Fitting and using growth curves.  Oecologia 49:
    293-299.
Kester, D.R., I W.  Duedall, D.N. Connors, and R M. Pytkowicz. 1967.
    Preparation of artificial seawater.  Limnol. Oceanogr.  12: 176-178.
Krauss, R.W. 1958.  Physiology of the fresh-water algae.  Annu. Rev. Plant
    Physiol. 9.  207-244.
McLachlan, J.  1959. The growth of unicellular algae in artificial and enriched
    seawater media.  Can. J. Microbiol. 5: 9-15.
McLachlan, J.  1964. Some considerations of the growth of marine algae in
    artificial media.  Can. J. Microbiol. 10: 769-782.
Morel, F.M.M., J.G. Rueter, D M. Anderson, and R.R.L. Guillard.  1979.  Aquil:
    a chemically  defined phytoplankton  culture medium  for trace  metal
    studies. J. Phycol. 15' 135-141
Murphy, L.S. and  R.A. Belastock   1980.  The effect of environmental origin on
    the response of marine diatoms to  chemical stress.   Limnol. Oceanogr.
    25:  160-165.
Nakanishi, M. and M Monsi   1965.  Effect of variation in salinity on
    photosynthesis of phytoplankton growing in estuaries. J. Fac.  Sci. Univ.
    Tokyo  9: 19-42
Nalewajko,  C  1966. Photosynthesis and excretion in various planktonic
    algae. Limnol. Oceanogr. 11: 1-10
Nicholas, D.J D  1963. Inorganic nutrient nutrition of microorganisms,  pp
    363-447, in  Plant  Physiology, Vol.  Ill  (F.C. Steward,  ed.), Academic
    Press, New York.
O'Kelley, JC 1974.  Inorganic nutrients, pp. 610-635,  in Algal Physiology
    and Biochemistry, Botanical Monographs No. 10 (WD.P. Stewart,  ed.),
    University of California Press, Berkeley
Ordog, V.  1981.   Statistical evaluation of the lexicological  algal bioassays.
    Acta. Hydrochim. Hydrobiol. 9  607-612.
Perry, M.J., C M. Talbot, and R.S. Alberte.  1981. Photoadaptation in marine
    phytoplankton:  response  of  the  photosynthetic unit.   Mar.  Biol. 62: 91-
    101.
Prat, S., J. Dvorakova, and M.  Baslerova.  1972.  Cultures of algae in  various
    media. Czechoslovak Academy of Sciences, Prague.
Provasoli, L. 1958.  Nutrition and ecology of protozoa and algae.  Annu  Rev.
    Microbiol.  12: 279-308.
Provasoli, L. 1966.  Media and prospects for the cultivation of marine algae.
    pp. 63-75, in  Cultures and  Collections of Algae.  Proceedings of the
    U.S.-Japan Conference held at Hakone, Sept. 12-15, (A. Watanabe and
    A. Hattori, eds.), The Japanese Society of Plant Physiologists.
Provasoli, L., J.J.A. McLaughlin, and M.R  Droop. 1957 The  development of
    artificial media for marine algae.  Arch. Mikrobiol.  25' 392-428.
Rehnberg, B.G., D.A. Schultz,  and R.L. Raschke.  1982. Limitations of
    electronic particle counting in reference to algal assays.  J. Water Pollut.
    Control Fed.  54- 181-186.
Reynolds, A.E., G.B. Mackiernan, and S.D Van Valkenburg. 1978. Vital and
    mortal  staining of algae in the presence of chlorine-produced  oxidants.
    Estuaries 1:  192-196.
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Rice, C P  and H C. Sikka.  1973.  Uptake and metabolism of DDT by six
    species of marine algae.  J. Agric. Food Chem. 21: 148-152.
Slovacek, R.E  and P J  Hannon. 1977.  In vitro fluorescence determinations
    of phytoplankton chlorophyll a.  Limnol. Oceanogr. 22:  919-925.
Boeder, C.  and E. Stengel  1974  Physico-chemical factors affecting
    metabolism  and growth  rate,   pp  714-740, in Algal Physiology  and
    Biochemistry,  Botanical  Monographs No.  10  (W.D.P.  Stewart, ed.),
    University of California Press, Berkeley
Stein, J.R. (ed ).  1973.  Handbook of Phycological Methods: Culture
    Methods and Growth Measurements.  Cambridge University Press, New
    York
Stephan, C E.  1977. Methods for calculating an LC50.  pp. 65-84, in
    Aquatic Toxicology and Hazard Evaluation (F L. Mayer and J.L. Hamelink,
    eds.), American Society For Testing Materials, STP 634, Philadelphia.
Stratton, G W.  1986  Medium composition and its influence on solvent-
    pesticide interactions  in  laboratory  bioassays   Bull  Environ. Contain.
    Toxicol. 36  807-814
Stratton, G  W  1987  Toxic effects of organic solvents on the growth of
    blue-green algae   Bull  Environ  Contam. Toxicol  38:  1012-1019.
Stratton, G  W.  and C T. Corke. 1981 a. Effect of acetone on the toxicity of
    atrazme towards photosynthesis in Anabaena  J  Environ. Sci. 1316.  21-
    33
Stratton, G.W  and C T  Corke  1981b  Interaction between  acetone and two
    pesticides towards  several  unicellular  green  algae.  Bull. Environ
    Contam. Toxicol. 27. 13-16
Stratton, G.W., R.E  Burrell, M.L. Kurp, and  C.T. Corke  1980.  Interactions
    between the solvent acetone and the pyrethroid insecticide permethrin on
    activities  of the blue-green  alga Anabaena.   Bull. Environ. Contam.
    Toxicol. 24: 562-569
Stratton, G W , R.E. Burrell, and C.T. Corke. 1982  Technique for identifying
    and minimizing solvent-pesticide  interactions  in  bioassays.  Arch.
    Environ. Contam.  Toxicol. 11: 437-445.
Tunzi, M.G., M.Y  Chu, and R C Bam. 1974.  In vivo fluorescence, extracted
    fluorescence, and  chlorophyll  concentrations  in algal  mass
    measurements. Water Res 8. 623-636.
Venkataraman, G.S  1969.  The Cultivation of Algae.  The Indian Council of
    Agricultural Research, New Delhi.
Vosjan, J.H and R T. Siezen.  1968  Relation between primary production
    and salinity of algal cultures.  Neth  J.  Sea Res. 4: 11-20.
Walsh, G.E. 1983.  Cell death and inhibition of population growth of marine
    unicellular algae by pesticides   Aquat Toxicol. 3:  209-214.
Walsh, G.E. and S.V. Alexander. 1980.  A marine algal bioassay method:
    results with  pesticides  and industrial wastes   Water Air Soil  Pollut. 13:
    45-55.
Walsh, G.E and R.L. Garnas. 1983.  Determination of bioactivity of chemical
    fractions  of liquid wastes using freshwater  and  saltwater  algae  and
    crustaceans.  Environ.  Sci  Technol.  17: 180-182.
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Walsh, G.E., K. Ainsworth, and A.J Wilson. 1977  Toxicity and uptake of
    Kepone in marine unicellular algae.  Chesapeake Sci  18: 222-223
Walsh, G.E , LH. Banner, and W B Horning.  1980  Toxicity of textile mill
    effluents to  freshwater  and  estuarme algae, crustaceans  and fishes.
    Environ. Pollut.  Ser. A 2V  169-179.
Walsh, G.E., K.M. Duke, and  R.B. Foster   1982. Algae and crustaceans as
    indicators of bioactivity of industrial wastes.  Water Res. 16:  879-883.
Walsh, G.E., C.H. Deans, and L L. Mclaughlin. 1987. Comparison of the EC50
    of algal toxicity tests calculated by four methods. Environ. Toxicol. Chem.
    6 767-770.
Walsh, G.E., M.J. Yoder, L  L. Mclaughlin, and E.M. Lores.  Responses of
    marine unicellular algae  to brominated organic compounds in six growth
    media. Ecotoxicol. Environ. Safety, in press.
Watt, W.D. 1966 Release of dissolved organic material from the cells of
    phytoplankton populations.  Proc. R. Soc. Lond Ser. B 164:  521-551.
Watt, W.D. 1969. Extracellular release of organic matter from two freshwater
    diatoms. Ann. Bot. 33:  423-437.
Yamane, A.M., M. Okada, and R. Sudo. 1984.  The growth inhibition of
    planktonic algae due to surfactants used  in washing agents.  Water Res.
    18: 1101-1105.
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     2.  Toxicity Tests with Marine Unicellular Algae

2.1 Introduction

Marine unicellular algae (phytoplankton, microalgae) are essential to  normal
function of marine (estuarine and oceanic) ecosystems.  As the main primary
producers, algae form the first link in food webs, oxygenate the water, and are
important in  cycling of dissolved organic  and inorganic substances. It is
important, therefore, to be  able  to  predict  possible effects of chemical
pollutants on  algal  populations with data  from  toxicity  tests on  sensitive
species.
    The  methods given here are static laboratory  toxicity tests for detecting
effects of single compounds and complex wastes on  growth of laboratory
algal populations, death of algal cells, and determination  of bioaccumulation
by algae in vitro.   Although specific  algal species are recommended, the
method may be used  with  other species,  either  unmodified or with slight
variations in light intensity,  temperature, or salinity in accordance with their
requirements. The test  is not designed to detect fate of toxicants. Effects on
growth and survival  in relation to initial concentration of parent compound are
expressed,  but effects of possible  degradation  products, behavior  of
chemicals  in the  test system,  or effects  upon  physical or chemical
characteristics of the growth  medium are not.

2.2 Definition of Terms

    Unicellular  Algae —   Members  of   the  Kingdom Plantae   whose
individuals  are composed of a single cell and whose growth form may  be
unicells,  chains,  or  groups.  Those  used in toxicity tests are phytoplankton
and are known as microalgae in contrast to the multicellular macroalgae.
    Axenic Culture —  Culture whose  living  components are  known.   In
axenic algal cultures, algal  species and bacterial contaminants have been
identified. Generally, axenic  algal cultures consist  of a single  species  without
bacterial  contamination.
    Growth Medium --  The liquid  in which algae are  cultured.  It consists of
a basic salt component in water that is similar  in composition to seawater and
to which  nutrients are added. It may also be made from natural seawater.
    Population  Growth -- Increase in number or  weight (biomass)  of algal
cells in a laboratory population. Cell size or morphology may change during
rapid population growth.
    Growth Rate -- Change in cell number or biomass of a  population over
a specific period of time.  This is generally expressed as a positive  integer,
but may be negative if a toxicant causes  death  and disintegration of cells
during the testing period.
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    Exponential Growth  Phase  --  Time  of  population  growth  in  vitro  at
which cell number increases exponentially.
    Population  Density  --  Number of  cells in,  or weight of,  an  algal
population  at a specific  time.   In algal toxicity tests, population density  is
estimated at the beginning  of a test and at one or  more times during the
period of exponential growth to allow calculation of the growth rate.
    Inoculum  Culture  -- Stock  culture of algae in  the  exponential  phase
that is diluted to a specific concentration of cells and added to test medium
    Untreated  Control Culture  -- Algal  culture that  is  an integral part  of
every toxicity test.  It is a culture that is prepared, incubated and analyzed as
all other cultures in the test, except toxicant and its carrier are not added.
    Carrier Control Culture -- Algal  culture  that is  an integral part of every
toxicity test in which a solvent carrier is used.  It is a culture that is prepared,
incubated, and analyzed  as all others in the  test, except it contains the same
volume of solvent carrier  as treated cultures, but without the toxicant.
    Rangefinding  Test (Screening  Test) —  Test conducted to determine
concentrations of a toxicant to be used  in the definitive test.
    Definitive  Test -- Test conducted to define the toxic  or  stimulating
concentration of a chemical.  It yields data for calculation of the IC50, LC50,
or SC20.
    IC50  (EC50) -- Interpolated or calculated  concentration  of a  toxicant
that would inhibit population growth  or any other biological process  of algae
by 50% compared  to  the controls in a  specific period of time.  This has also
been  called the RC50 (concentration that reduces growth by 50%).  The term
RC50 is not recommended here because it is  an erroneous expression  of
effect. Toxicity causes a lower growth  rate  in relation to control growth:  it
does  not reduce growth rate in treated cultures.
    LC50 -- Interpolated or calculated  concentration  of a toxicant that
would kill 50% of the cells in a specific  period of time.
    SC20  ~ Interpolated or calculated concentration  of  a  substance  that
would cause population density  of a treated culture to be 20% greater than
the controls in a specific  period of time.
    NOEC  --  No  observed  effect concentration.   This  is  the highest
concentration of a substance that had no observed effect in a toxicity test.
    LOEC --  Lowest  observed  effect  concentration.  This  is  the lowest
concentration of a substance that caused an observed effect in a toxicity test.

2.3 Personnel

    Personnel designated to perform toxicity tests with algae must be trained
in the principles and techniques of  phycology and microbiology.  Successful
maintenance of axenic cultures, sterile  transfer, identification of deviations
from  normal morphology, early  detection of problems, and numerous other
aspects of algal culture and testing  can be accomplished only by scrupulous
attention to details by  knowledgeable people.

2.4 Safety

    Safety of laboratory  personnel  must be insured before initiation of algal
tests  with toxic substances and  solvent carriers.  Manufacturer's  data sheets
                                   17

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and other sources of information on effects of the test  material  on human
health must be consulted and proper safety measures applied before testing.
Care is especially important when working with liquid complex wastes, where
contents  of the mixtures may be unknown.  Operators must wear protective
clothing (laboratory coats, gloves, respirators) whenever exposure  may occur
to skin or by inhalation, suitable absorbants for carrier and toxicant  spills must
be at hand, and the  laboratory must be well-ventilated.  All liquids  must be
transferred by automatic pipette, never by mouth, and flame or sparks must
not be present when  solvents are used.  Stock solutions must be stored in a
refrigerator equipped with a spark-free motor.  Laboratory coats, gloves, and
respirators must be worn when cleaning contaminated glassware with solvent.
    When  algal tests  are  done  for EPA, each  laboratory must have an
approved,  detailed, written  safety  plan  that describes  methods  for  safe
handling  of toxicants and solvents.

2.5 Disposal of Toxicants

    The  testing  laboratory  must have a written plan,  approved by  EPA, for
safe  disposal of toxicant stocks and stock dilutions in  solvent, contaminated
growth  medium with algae, solvent  used  for  rinsing  glassware,  and
contaminated  equipment such  as  pipettes, laboratory coats,  gloves,  and
absorbant used to clean up  spills.  Disposal will generally require employment
of a commercial company licensed  by the State for hauling and disposing of
toxic waste according to RCRA regulations

2.6 Quality  Control

    The  best quality control that can be  applied  to  algal toxicity  tests is
related to competent personnel, close adherence to all aspects of the method
as described, and  consistency  in  day-to-day operations.   Careful quality
control must be applied to maintenance of algal stock cultures, control of light
intensity  and  temperature, rigorous cleaning of  glassware,  a draft-free
working  area, application of  microbiological techniques  for maintenance of
sterility, and periodic testing for bacterial contamination of stocks.
    When algal tests are done for EPA, each laboratory must have a detailed,
written quality control plan that describes requirements  for culturmg and
testing of algae. A laboratory notebook that records data showing adherence
to good  laboratory  practices required  by EPA  should  be available for
inspection by the Project Officer.

2.7 Chemical and  Physical Properties  of Test Substances

    Chemical and physical  properties of toxic substances and solvent carriers
should be known before the test begins.  They can often be obtained from the
manufacturer, seller,  or  handbooks on such  properties, and are  used for
setting toxicant  concentrations  and  interpretation of results.   Information is
required  on  solubility, volatility,  vapor  pressure,  rate of  decomposition in
water, and octanol-water partition coefficient.
                                   18

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2.8 Chemical Analyses of Test Substances

    Chemical analyses must  be performed to confirm identity and purity of
the toxicant and to determine percentage recovery in growth medium before
initiation of algal tests  Quantitative analyses  must also be done on medium
that contains the concentrations of toxicant used in each test.  Identification
and  quantitation of major  organics, anions,  cations,  PCV, and NC>3~ in
complex mixtures is also desirable, and results of chemical analyses should
be submitted with test results. When algal tests are done for EPA, the testing
laboratory  must have  an approved, detailed, written set of protocols for
chemical analyses, including a plan for quality  control

2.9 Equipment

GLASSWARE    All glassware must be of borosihcate glass or equivalent.
Glassware used for stock cultures and in toxicity tests should be capped with
stainless  steel closures or  foam plugs.  Flasks and closures distributed by
Bellco  Glass Co , Vmeland, NJ,  work well. Foam plugs  may be used only
once because  they absorb volatile  chemicals.   Their use  is  discouraged
because they must be disposed of as solid  waste.
    Volume of growth  medium  used for maintenance of algal stocks should
be limited to an amount easily handled for sterile transfer.  It is suggested that
200  ml of  growth medium in a  500 ml  volume Erlenmeyer flask  is  a
convenient  system  because  sterile  transfer  is difficult with larger  flasks.
Volume of growth medium  should  not exceed  one-half  that  of  the
Erlenmeyer flask, whatever  the volume.
    Flasks  of 125 ml volume are used in toxicity tests.  If heavy metals are to
be  tested,  the  flask  should be  coated with  silicone film such  as General
Electric SC-87  dry film (Pierce  Chemical Co., Rockford,  IL) or equivalent.
The method for silicone coating was  described by  Davey et  al.  (1970).  Use
2 5 - 5.0% SC-87 in cyclohexane to coat the flasks.   Swirl the solution to
cover the flask  wall, dry  in  air, cure  at  150 -  175 C  for  4 h, rinse with
deionized  or  glass-distilled water, and dry again.  Inspect all  flasks  after
each test and recoat over the old silicone layer if necessary
    Fernback flasks of 2.8 L volume are used in bioaccumulation  studies.
    It is necessary to use clean flasks that are not scratched inside because
such flasks cause precipitation of salts from growth medium.  Medium in all
flasks should be examined for precipitated salts before each test
    Glassware must be washed thoroughly to avoid carryover of toxicant from
test to test.  When  a test is completed,  dispense all contaminated algal
cultures to a  safe container  and  rinse three times with acetone into  the
container.   Rinse the flasks with tap water and  soak them overnight in 1N HCI,
scrub in phosphate-free detergent, rinse 10 times with tap water and three
times with  glass-distilled  or  deionized  water, dry  in an  oven, and store
capped in  a draft- and dust-free  room
GROWTH CHAMBERS   Separate growth  chambers must be maintained for
algal stock cultures and toxicity  tests  They  must be  kept  under identical,
carefully controlled conditions of  light (quality  and intensity) and  temperature.
Light should be from  cool  white fluorescent  tubes, with  variable control of
                                   19

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light-dark cycles  or  continuous lighting.   Intensity may  vary  with  algal
species, but is generally between 50 and 150 pE rrv2 sec~1.  Intensity may
be controlled by rheostat or by placing cultures at selected distances from the
fluorescent  tubes.  Light intensity  in the tests recommended here may  be
between  100 and  125  p,E m-2 sec-1  (590-735  ft can;  6,350-7,900 lux) at
the surface of the  growth medium. When light intensity falls below 100 pE
nrr2 sec-1, the fluorescent tubes should be replaced.  Intensity of light from
new tubes falls rapidly during the first four days of use and remains constant
for many days thereafter  Therefore, it is best if tests are not initiated until
four days after the fluorescent tubes are replaced.
    Temperature in the growth chamber may also vary with requirements of
individual algal  species.  Generally, a chamber  that can maintain constant
temperature between  10 and 25 C (±0 5 C) is adequate  Temperature in the
test described below is 20 C.
LIGHT METER   Light intensity must be monitored at least once a day at the
level of the surface of the growth medium.  The light meter must be calibrated
against a standard, and  measurements must be recorded daily.
TEMPERATURE MONITOR   A  device  for continuous   recording  of
temperature must be installed in the growth chamber  It should read in °C,
and all original temperature records should be kept in a permanent file.
MICROSCOPE   A microscope with resolving power that  allows detailed
examination of algal cells is needed for checking cell morphology.  It must
have a mechanical stage that accepts a hemacytometer for counting cells.
STERILIZATION OVEN  Algal  growth  medium  is  sterilized by heat.  The
sterilization oven must be large enough to  contain all flasks of each toxicity
test and must maintain its temperature at 60 C for 4 h.
AUTOCLAVE    An autoclave  is  used to sterilize everything other than
growth medium. The autoclave must have a  drying cycle to  insure dry
glassware and filters.
PIPETTORS Medium  for toxicity tests is added to exposure  flasks  with a 50-
ml volume pipettor. The Ace Glass (Louisville, KY) Volumetril Bulb and 500-
ml volume flask  work well.  Nutrients are added  with Eppendorf pipettes  (or
equivalent)  fitted with disposable tips.   Metal and vitamin additions require
sterile tips.  Sterile, disposable glass pipettes are required for culture transfers
and sampling.
HEMACYTOMETER  A hemacytometer is  needed  to estimate  population
density of inoculum cultures and for enumeration of cells in toxicity tests.
HAND TALLEY  A multi-channel hand  talley device is required for counting
cells on a hemacytometer and for differential counts of living  and dead cells.
ELECTRONIC CELL COUNTER  An electronic particle counter may be used
to estimate  population  density of algae that occur as unicells,  but  not as
doublets, chains, clumps, etc.  It is desirable to have an attachment to the
counter for estimation of average cell volume.
SALINOMETER  A hand-held  salinometer  is required  to check  salinity of
growth medium and raw liquid waste
VISIBLE  LIGHT SPECTROPHOTOMETER Population   density  may  be
estimated with a  visible light spectrophotometer equipped with variable
wavelength control and a 10-cm light  path.  This equipment may be used
                                  20

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when the only particles in the culture are algal cells,  the population is in the
exponential phase of growth, and the medium is not highly colored
FLUORESCENCE SPECTROPHOTOMETER  Population density  may  also
be estimated by fluorescence spectroscopy of intact cells.  This  method is
very sensitive, especially at low population density.
ROTARY SHAKERS Cultures in algal toxicity tests must be shaken gently to
insure exchange of oxygen and carbon dioxide between the atmosphere and
growth medium, and to maintain the cells in suspension for optimal utilization
of nutrients and light.
pH METER  pHs of stock and test media are measured and recorded before
each transfer or test.
CENTRIFUGE   A high-speed  centrifuge  is  used  in  studies  on
bioaccumulation.  Buckets may be up to 500 ml  in volume and  lined with
Teflon   (E.I.  DuPont  de  Nemours, Newtown, CT) or equivalent,  but never
metal.
MAGNETIC STIRRER     Magnetic stirrers are used for preparation of growth
medium and resin for cation removal.

2.10    Test Species

Algal species used in toxicity tests may vary in accordance with requirements
and objectives of the tests, and the method given here should accommodate
most marine unicellular algae after slight modifications of salinity or  nutrients.
    If a  specific  species is not  required, the  test  species should be
Minutocellus polymorphus Hasle, von  Stosch and Syvertsen (1983).   This
species,  earlier called  Bellerochea polymorpha  by Margraves and  Guillard
(1974), is found  in estuaries  and the open ocean, is easily cultured, and is
sensitive to toxicants (Fisher et al., 1972; Fisher,  1977).  In the United States,
M. polymorpha can be obtained from the Bigelow  Laboratory  for Ocean
Studies, West Boothbay Harbor,  Maine 04755.   It is suggested that Clones
675D, BCN, or SD be used  in toxicity tests because they are oceanic and
thus tend to be  more sensitive to  most toxicants  than  clones from inshore
waters.  However, Clone SAY 7, isolated from an estuary, may also  be used.
    An important consideration for use  of M. polymorphus is its rapid growth
in culture.  Toxicity tests  can be completed after 48 h growth, thus reducing
the  influence of photodecomposition, volatilization,  and adsorption  of toxicant
that may occur in tests of longer duration.
    Starr (1971) and Rosowski and Parker (1982) have identified laboratories
from which algal cultures may be obtained.

2.11    Axenic Culture

Axenic cultures of algae are uncontaminated by bacteria or other organisms.
Algal  cultures used in toxicity tests should be axenic and tested for the
presence of bacteria at approximately monthly intervals.
    The  ATCC Media Handbook (1984) gives  formulations of  media for
detection of bacterial contamination At least two  media should be used:
          LBacto Peptone   	    10.0 g
           Succmic Acid  ...     	  1.0 g
           (NH4)2SO4  ...        	  1.0g
                                  21

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          MgSO4-7H2O	     1.0 g
          FeCI3-6H20   	      2.0 g
          MnSO4-H20	   2.0 g
          Synthetic Seawater                          1.0 L
         2. Bacto-Tryptone Yeast Extract   	   5.0 g
          Glycerol 	   3.0 g
          Synthetic Seawater  	    750 ml
          Distilled or  Deionized Water  	   250 ml

    Synthetic Seawater

          NaCI 	   27 5 g
          MgCI2   	   5.0 g
          MnSO4 7H20  	   2.0 g
          CaCI2 	   0.5 g
          KCI  	   1.0 g
          FeSO4   	   1.0 g
          Distilled or  Deionized Water  	   1.0 L
          Adjust to pH 6.8 with KOH
    Dispense  10 ml  of medium into  test tubes,  cap with stainless steel
closures  or foam plugs, and sterilize by autoclaving at 121 C for 15  min.
Inoculate the sterile media with 0.25 ml of stock algal culture and incubate at
20 C   Examine the media for bacterial growth daily for seven days.  After
seven days, streak ahquots of the  media on  1.5% agar prepared with  the
bacterial  media and incubate at 20 C for seven days.
    If bacterial  contamination is detected, the stock culture must be purified
or a new culture obtained.  Techniques  for purification are  given by Stein
(1975). The easiest  method is by  treatment with  antibiotics,  and  the
techniques  described  by Stein (1975) for purification in liquid and on  agar
should be used.

2.12    Growth Medium

BASIC MEDIUM The algal growth medium is a modification of that described
by Morel et al  (1979).  This medium, called  "Aquil," is completely artificial
and chemically  defined.   It is designed to reduce contamination by trace
metals and  to  contain  nutrient  concentrations similar to those  of natural
seawater, thus precluding complications due to precipitation of salts. Morel et
al. (1979) recommended removal of cations from the major salt and nutrient
solutions by use of an ion exchange column.  This  step may be used when
the toxicants in question are heavy metals,  but it  is possible that the ion
exchange process  may  modify  the medium and  introduce contaminants.
Untreated medium can be used with all other toxicants. Separate algal stocks
should be maintained  in both media.
    Formulations of salt  and nutrient solutions are given in Table 1.  The
sequence of steps in preparation  and inoculation of 1 L of growth medium is:
    1    Dissolve all salts, except MgCI2-6H2O, in  approximately  750  ml of
glass-distilled  or deionized  water in  a 1-L  volumetric flask.   The  water
should have a resistivity of at least 18 megohm-cm at 25 C.
    2    When all of the salts have dissolved, add the MgCL2-6H20.
                                   22

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    3.  When  the MgCl2'6H2O has dissolved, add 0.25 ml  of each  of  the
       NO3~,  and SiOa"  nutrient  solutions.
    4.  Bring to 1 L volume with glass-distilled or deiomzed  water. Salinity
should  be approximately 35  parts  per  thousand.   Check salinity with a
salinometer.
    5.  Filter the growth medium through a 0.45 jam porosity filter washed
previously with 1 L of deiomzed or distilled water.
    6.  Dispense into culture flasks. Add approximately 200  ml to each 500
ml volume Erlenmeyer flask for stock cultures.  Add 50 ml to each 125 ml
volume Erlenmeyer flask with a volumetric bulb.  Dispense approximately  1 L
into each Fernbach flask for bioaccumulation studies
    7.  Heat sterilize in an oven at 60 C for 4 h.
    8.  Immediately before the test, mix equal volumes  of  the  metal and
vitamin solution, sterilize by filtration, and add 2 ml to each stock culture flask
with  200 ml growth medium, 0.25  ml to each test flask with 50  ml growth
medium, and 5 ml to each liter of medium in bioaccumulation studies
    9.  Use  a sterile membrane filter (0.45 jam porosity)  and non-metallic
filter holder affixed to a sterile syringe for sterilization of the metal and vitamin
mixture. Filter into a sterile capped tube and add to growth medium with an
Eppendorf pipette equipped with a sterile tip.
    10. For toxicity tests, add toxicant in no more than 0.025 ml solvent
carrier to  medium in exposure flasks; add the same volume to medium in
carrier control flasks   All flasks  must receive the same amount  of solvent
carrier.  Reserve other flasks without carrier to serve as untreated controls.
    11. Add 1 or 2 ml of old stock at the end of the exponential growth  phase
to 200 ml fresh medium  for  maintenance of  algal stocks.  For toxicity tests,
add 1 ml of inoculum culture, prepared as described below, to 50 ml growth
medium.  These transfers  must  be done by  microbiological methods that
insure sterility.

2.13    Medium for Use in Studies on Toxicity of Heavy Metals

Contaminating cations  may  be  removed  from the basic salt  and nutrient
solutions before tests for heavy metal toxicity in water.  The method for  cation
removal was given by Morel et al. (1979). Their report should be  consulted
before proceeding with this  test,  which  should never be used with acetone
carrier.  A chromatography column, packed with  resin that retains  cations by
chelation, is used to strip impurities before the  salts and  nutrients are mixed.
For one column:
    1.  Use  Chelex  100  resin  (drymesh  100-200,  Na form;  Bio-Rad
Laboratories, Richmond, CA).
    2.  Rinse 15 g resin for 5 min in approximately 200 ml methanol in a
400-ml  beaker.
    3.  Rinse the resin three times in glass-distilled or deiomzed water.
    4.  Add  300 ml of the  solution to be cleaned and, while stirring on a
magnetic stirrer, titrate very slowly to pH 8 (±0.1) with 1N  NaOH for the salt
solution and 1N HCI for PO4", NC>3~, and SiOa" solutions. Titrate until  pH is
stable for at least 30 min.
    5.  Fill a 10 x 250 mm glass chromatography column with the  solution to
be cleaned  A column with a reservoir at the top will save much time.  While
                                  23

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Table 1. Composition  of Salts and  Nutrients to be Used in Culturing
and Testing Marine Unicellular Algae (Morel et al.,  1979)
Substance1
NaCI
CaCI2-2H20
KBr
NaF
KCI
H3B03
Na2SO4
NaHC03
SrCI26H2O
MgCI26H2O2

QL-1
24.53
1.54
0 10
0.003
0.70
0.03
4.09
0.20
0.017
11.1

1 The first nine substances are weighed previously to the test.  Several batches of dry salts
may be prepared at one time and stored in tightly capped glass containers for use when
needed.  Since it is convenient to prepare two liters of medium for each test, batches of
salts that contain twice the amounts given here may  be stored and used to prepare growth
medium in glass-distilled or deionized water
2 The MgCI2 6H2O is dried at 104 C, stored  in a desiccator, and added only after the
other salts have dissolved.
Nutrients
1.Dissolve  1.38 g Na2HPO4-H2O and 5.26 g NaCI in 1  L glass-distilled or  deionized
water.
2.Dissolve 8.5 g NaNO3 in 1 L glass-distilled or deionized water . Ad)ust pH to 8.0 with
INNaOH.
3.Dissolve  3.55 g Na2SiO3 9H2O and 4.38 g NaCI in 1  L glass-distilled or  deionized
water. Adjust pH to 8.0 with 1N HCI.
Trace Metals
1.Dissolve 0.47 g Na2EDTA and 0.031  g FeCl3'6H2O in approximately 300 ml glass-
distilled or deionized water in a 500 ml volumetric flask. If heavy metals or liquid waste are
to be tested, use one-half of the iron concentration and prepare this solution without
EDTA immediately before the test
2.Dissolve 0 249 g CuSO4 5H20  in 1 L glass-distilled or deionized water.1
S.Dissolve 0.265 g (NH4)6Mo7O24 4H2O and 0.595 g CoCI2-6H2O in 1 L glass-distilled
or deionized water.1
4.Dissolve 0.455 g MnCI2-4H2O and 0.115 g ZnSO4-7H2O  in 1 L glass-distilled  or
deionized water.1
                                       24

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the solution is dripping at about 40 ml min'1, pour the resin slurry that was
5.Add 0.25 ml of 2, 3, and 4 to 1  above and take to volume. This if the metals working
mix.
1 Unused portions of these solutions may be frozen for up to a year for later use.
Vitamins
1.Dissolve 110 mg Vitamin  8,2 in  100 ml glass-distilled or deionized water.
2.Dissolve 10 mg biotin in 100 ml glass-distilled or deionized water.
3.Add 0.025 ml Vitamin B12 and  0.25 ml biotin solutions to approximately 75 ml glass-
distilled or  deionized water in a  100  ml volumetric flask.   Dissolve  0.005 g thiamin
hydrochlonde in it and take to volume.  This is the vitamin working mix. Keep frozen when
not in use.

adjusted to pH 8 into it  at a constant rate and without interruption to insure a
continuous, homogeneous column of resin.
    6.  After  all of the slurry has been added, continue flow of salt or nutrient
solution until the column is completely packed.
    7.  Pass the solution to be cleaned through the column at  the drip rate of
5  ml min'1.
    8.  After  it has passed through the column, bubble air vigorously through
the solution to return the pH to 8.   The air should  be  filtered through a cotton
plug.
    9.  Prepare  separate columns as above for the salt, PCV, NC>3~,  and
SiC>3~ solutions. The metal and vitamin solutions are  not stripped  of cations.
    10.  After the pH  is returned to 8,  medium is prepared as described
above for  nonstripped medium.
    11. Resin should be replaced after 50  L  of salt solution or  100 L of
nutrient solution  have  eluted.  It should  also be   replaced  if it  becomes
discolored.
    12  The columns may be kept at room temperature when  not in use,  but
they must not become dry. If the  resin breaks, or if any part of it dries out, it
must be regenerated to pH 8 and replaced
    It is suggested that several columns for stripping  the salt solution be used
simultaneously because this step  is time-consuming.


2.14   Medium for Use with Tests on Liquid Complex Mixtures

Follow instructions for preparation  of medium  as described above, except use
liquid waste instead of water in the  salt solution.  Do not filter the waste before
adding  salts unless  algae are present, and do not  sterilize.  Flasks used in
waste  studies  should  be  coated  with  silicone  as  described above.
Polycarbonate flasks may also be  used.  Prepare the metal solutions (Table
1) without EDTA.
    Liquid waste must be  collected, stored,  and  shipped  in  unreactive
containers at 4  C and tested as soon  as  possible after  receipt at  the
laboratory.  If the waste cannot be analyzed immediately, store it in the dark
at approximately 4 C. Characteristics such as pH, salinity, color, smell,  and
presence  of solids should be reported with results of toxicity tests.
                                    25

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ESTIMATION OF POPULATION DENSITY Three  methods  for estimation  of
population  density are acceptable:  cell  counts,  light  spectroscopy, and
fluorescence spectroscopy.
    1 .Cell counts -- Estimation of cell numbers may be  made by  counts on
a hemacytometer.   A sample is taken with a sterile  pipette after vigorous
swirling of the culture and added to both sides of the hemacytometer. All cells
in the four corner and one central squares of each chamber are counted with
a multi-channel  hand tally.   The  total is the number  of  cells m a  cubic
millimeter of culture  medium.  This  method has  the advantage  of  visual
inspection of algal cells,  and those of abnormal  morphology may be  noted
during the counting  procedure.   It is,  however, time-consuming,  relatively
imprecise,  and  considerable precision is lost as  cell  numbers  decrease.
Photomicrography  of  hemacytometer preparations with subsequent  image
analysis is acceptable for estimation of population density.
    Cells may be enumerated on an electronic particle counter.  This method
is more rapid and precise than the hemacytometer method,  but it can be used
only with species that  occur as unicells.
    Minutocellus polymorphus occurs as unicells  in cultures up to 3 days old.
Cham formation  sometimes  occurs in older  cultures, and  electronic particle
counters cannot be  used to estimate  population  density.  Since the test
described here requires only two days, chain formation is of little importance.
    If an electronic particle counter is used, growth medium, metal mix and
vitamin mix should be filtered  through  a 0.22 u,m  porosity  filter  before
sterilizing, and an unmoculated blank sample of medium prepared for  use in
instrument calibration  with regard to background particle interference.  This
method is used  best with  a  particle size  distribution  meter  to  determine
influence  of  toxicant  concentration on cell size.   All  cultures  should be
examined microscopically for abnormal cells when counts are made  on  an
electronic particle counter.   If  appreciable  numbers of abnormal cells  are
present, estimate their percentage by  a  differential count  of 100  cells.  In
order to determine the IC50 as described below, calculate the average counts
for control, solvent carrier control, and each treatment culture.
    2.Light spectroscopy  — Light spectroscopy  is a rapid, efficient way to
estimate population density, provided that the only  particles in suspension in
growth medium are algal cells.  The spectrophotometer must be calibrated to
zero  with growth  medium  before each  test,  and  checked  again  for
maintenance of  zero  calibration after the  series of absorbance readings  is
completed.  The spectrophotometer  should  be equipped with a recorder for
producing a printed direct readout of  results   Keep the printed readout in the
laboratory notebook   Absorbance of the cultures  must be measured across a
10-cm  light  path  to  insure  precision  at  low population  density and at  a
wavelength specific for the  algal test species  This  may  be determined  by
scanning  between  wavelengths  of 500  to 700 nm  and  choosing  the
wavelength that  produces the highest optical density with  a culture of algae.
The wavelength  is approximately 680 nm for M.  polymorphus.   Examine the
cultures microscopically for abnormal  cellular  morphology.  If appreciable
numbers  of  abnormal  cells are  present,  estimate their percentage  by
differential counts of  100 cells   In order to determine the  IC50 as described
                                   26

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below, calculate the average optical density for each control, solvent carrier
control, and treatment group.
    3.Fluorescence spectroscopy  —  Fluorescence spectroscopy  is  also a
rapid and efficient method for estimation of population density when the only
particles in suspension are algal cells. The fluorescence spectrophotometer
must be calibrated according to the manufacturer's specifications before each
test  and calibrated to zero with  growth  medium  that contains the  highest
concentration of toxicant used in the test. If toxicant fluorescence is detected
at the same wavelength as  algal fluorescence, this method cannot be used.
The spectrophotometer should be equippped with a recorder for  printed direct
readout of results.  The printout  must be kept in the laboratory notebook.
    Wavelengths of excitation and  analysis must be determined  (see  Mitchell
and Kiefer, 1984, for a discussion of absorption and excitation spectra).  This
is done by determining  fluorescence emission  at  a  specific  emission
wavelength  while  scanning with  excitation wavelengths  The excitation
wavelength at which emission was greatest is then  held constant while the
emission  wavelength  scale is  scanned for greatest emission.   The final
excitation and  emission wavelengths may be determined by a series  of such
steps,  using  a scanning  range  more  narrow  than the  previous one.
Wavelengths for M. polymorphus are  approximately 443 nm (excitation) and
643  nm (emission).  Examine the  cultures microscopically for  abnormal
cellular morphology   If appreciable numbers of abnormal cells are present,
estimate their  percentage  by differential counts of  100  cells.   In order to
determine the  IC50 as described below, calculate the  average  fluorescence
values for untreated control, solvent carrier control, and each treatment group.
Average fluorescence of the carrier controls should  be  similar to average
fluorescence of the untreated controls. Subtract average fluorescence of Aquil
medium from average fluorescence of the control and treatment cultures for
final fluorescence of the cultures.

CALCULATION OF THE IC50

The  IC50 may be calculated by straight-line graphical interpolation  (APHA,
1985; Walsh et al., 1987).  Plot  the toxicant  (active  ingredient in  formulations)
concentration on  the y axis and the  percentage inhibition on the x  axis of
semi-logarithmic graph paper.   Plot the concentrations that inhibited growth
just above ana below 50%  and draw a line between them.   Interpolate the
IC50 as shown in Fig. 3.
                                  27

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CALCULATION OF THE GROWTH RATE

    Growth rate (u.) is calculated from the expression
                                   t-t
                                       o

Where N = population density at the end of the test
        N0 = population density at the beginning of the test
        loginNo = 4.69
        t - t0 = length of time of the test (2 days).
Calculate  p.  from average cell  numbers, optical density, or fluorescence
emission of control, solvent carrier control, and each treatment group.

Figure 3. Graphical interpolation of the IC50.
        3 -
   as
   c
    10
   I
2 -
                                                     SC20 = 26 mg/l
                             TO        15

                           Waste-Control, Cells
                                               20
                                                 25
                                                           30
                                  28

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2.15    Fractionation Procedure for Liquid Complex Wastes

If a complex waste inhibits or stimulates algal growth, it is often  desirable to
identify its bioactive constituents   This may be done by a method described
by  Walsh and  Garnas (1983), which  combines  chemical  fractionation and
biological  testing to identify  bioactive organic  and  inorganic fractions
Bioactive fractions or subfractions may  be analyzed chemically to identify
toxic or stimulatory substances. Details of this procedure are given below

2.16    Test for Living and Dead Cells

Algal  growth tests do not indicate  whether  a toxicant  simply  inhibits
population growth  or kills  cells directly.  It may be desirable to know if a
compound kills algae because, presumably, substances that kill  are of more
potential danger than those that inhibit population growth.  In this case, algal
populations early in the exponential growth phase are exposed to a toxicant
for 24 h, and differential counts of living and dead cells  are performed. Dead
cells are dyed by the mortal stain, Evans blue, in contrast to unstained living
cells.  Skeletonema costatum should be used in this test because  the cells
are large and easy  to identify.

2.17    Bioaccumulation

Algae accumulate  toxicants by   adsorption  to  the cell  surface  and  by
absorption into cells.  Thus, they constitute the first link in food chain transfer,
whereby toxicants may be transferred to higher trophic levels. Ability of living
algae to accumulate toxicants is estimated by exposure  of populations in  the
exponential phase of growth to various concentrations in  the medium  for 24 h,
with subsequent analyses of cell  concentrations.  It is important that growing
populations,  where over 99% of  the cells are living, are exposed  because
dead cells also adsorb toxicants.

2.18    Documentation and Reporting of Results

When algal  tests  are  done for   EPA a  notebook  that contains  detailed
descriptions  of methods and quality control procedures  used in testing must
be kept in the laboratory at all times.  All data from toxicity tests  must be
entered  in this notebook and these data used for compilation of reports to
EPA.

2.19    References

APHA, 1985   Standard Methods For the Examination of Water and
    Wastewater,  16th  ed , American  Public Health  Association, Washington,
    DC.
ATCC, 1984.  Media Handbook  American Type Culture  Collection. Rockville,
    MD.
Davey, E.W., J.W. Gentile, S.J. Erickson, and P Betzer   1970. Removal of
     trace metals from marine culture media   Limnol.  Oceanogr.   15: 486-
    488
Fisher, N.S  1977. On the differential sensitivity of estuanne and open-
    ocean diatoms to exotic  chemical stress.  Am. Nat.  111. 871-895
                                  29

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Fisher, N S , L.B  Graham, and E J Carpenter.  1972. Geographic differences
    in phytoplankton sensitivity to PCBs.  Nature 241: 548-549
Hargraves, P E. and R R L. Guillard  1974. Structural and physiological
    observations on some small marine diatoms.  Phycologia 13: 163-172.
Hasle, G.R., H.A. von Stosch, and E.E  Syvertsen.  1983.  Cymatosiraceae, a
    new diatom family  Bacillaria 6. 9-156
Mitchell, B.G. and D A  Kiefer. 1984. Determination of absorption and
    fluorescence  excitation  spectra for phytoplankton.   pp.  157-169, in
    Lecture  Notes on Coastal and Estuarme Studies  (O.  Holm-Hansen, L.
    Bolis  and R. Gilles, eds.), Springer-Verlag, New York.
Morel, F M M., J.G. Reuter, D.M. Anderson, and R.R L. Guillard.  1979.  Aquil:
    a chemically defined phytoplankton  culture medium  for  trace  metal
    studies  J.  Phycol. 15  135-141.
Rosowski, J.R. and B C. Parker (eds.)  1982  Selected Papers in Phycology
    Phycological Society of America, Inc. Lawrence KS
Starr, R.C  1971. Algal cultures - sources and methods of cultivation,  pp.
    29-53,  in Methods  in  Enzymology, Vol. 28 (A. San Pietro,  ed.),
    Academic Press, New York.
Stein, J R (ed.).  1973  Handbook of Phycological Methods:  Culture
    Methods  and Growth  Measurements. Cambridge University Press, New
    York.
Walsh, G.E. and  R.L Garnas. 1983. Determination  of bioactivity of chemical
    fractions  of  liquid  wastes using freshwater and  saltwater algae  and
    crustaceans.  Environ  Sci. Technol. 17: 180-182.
Walsh, G E., C.H. Deans, and L.L McLaughlin 1987.  Comparison of the  EC50
    of  algal  toxicity tests calculated by four methods.   Environ. Toxicol.
    Chem.   6.767-700.
                                  30

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          3.   Growth Test with Single Substances
3.1 Preparation of Toxicant

If the toxicant is soluble in growth medium at the highest concentration to be
used  in a test,  a saturated solution in  growth medium should be  used as
stock. Have this stock analyzed for purity and concentration.
    If the toxicant is of low solubility in growth medium, several days before
the test is to begin prepare a stock solution in nanograde acetone carrier on a
weight to volume basis. Dissolve enough in  the acetone so that, when 0.025
ml is  added to 51  ml of growth  medium, the concentration will approximate
the saturation concentration.   Have this stock analyzed  for  purity  and
concentration  and store in a sealed flask in an  explosion-proof refrigerator.
Express results of chemical analyses as  concentration of the toxic substance,
whether it will be tested as a single substance or as the active ingredient in a
formulation.
    When toxicant purity and concentration have been  confirmed, determine
the highest concentration  of toxicant that can be used in the test.   This  is
done  by adding 0.025 ml of the stock to  51 ml of growth medium. If crystals
do not form, this concentration can be used as the highest in the toxicity test.
If crystals form and do not go into solution with swirling  of the  medium, dilute
the stock slightly and test  again for crystal formation. Continue until crystals
do not form.   This will be the highest concentration  used in  the test.  This
method cannot be construed to estimate  the saturation concentration, but it is
a practical way to determine highest test  concentration.

3.2 Toxicant Concentrations

The highest concentration of toxicant to be  used in a test is  determined as
above, and  lower concentrations are percentages of it.  Use volumetric flasks
for  making  dilutions  of  toxicant  stock.    In  rangefinding  tests,  the
concentrations are widely  separated to estimate the  IC50  and establish
chemical concentrations  for the  definitive test.    Use  at least five
concentrations, such as 0.01, 0.1,  1, 10, and  100%  of  the  concentration
determined above. All flasks should receive the same  volume of toxicant in
carrier, and acetone stock must be diluted so that 0.025 ml is added for each
concentration. Convert percentage to weight of toxicant added and calculate
the  concentrations.   Toxicant  stock and dilutions should be stored  in  an
explosion-proof refrigerator.
    If the substance is toxic to  algae in the rangefinding test, use at least five
concentrations of toxicant that encompass the estimated IC50 in the definitive
test.   In most cases,  each concentration should be at least 60% of the next
                                   31

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higher  For example, if, in  the rangefinder, there was  no inhibition of algal
growth at 10 ppm  (parts per million)  and total inhibition  at  100 ppm, use
concentrations of 13, 22, 36,  60, and  100 ppm in the  definitive test.  This
sequence,  based on 60%,  may  be unacceptable in some cases, such as
when there is a narrow concentration  range between no  inhibition and total
inhibition of growth.  If, for example, the IC50 is between 5 and 10 ppm, then
the series, 5, 6, 7, 8, 9, and 10 ppm (six concentrations) should be used.
    It is clear  from the above  that there cannot be  a  single  method  for
determining concentrations in definitive tests, but that they must be chosen in
relation to algal response. Overall, response must be graded in relation to the
series of concentrations.  It is best if at  least one concentration inhibits growth
by  between  55 and  75%,  and  another  concentration inhibits  growth  by
between 25 and 45%.  These  criteria insure that responses to concentrations
used  to calculate the IC50 are statistically different from each  other, and that
population densities in treated flasks are significantly different from densities
in control flasks

3.3 Test Procedure

Day 1      a. Prepare 2  L of algal growth medium  (chelexed or nonchelexed)
             as described on page 24, dispense 50 ml into each of 40 125-
             ml culture flasks; cap with stainless steel closures or previously
             unused foam plugs; label the flasks:
                3 control flasks
                3 solvent carrier flasks
                15 treatment flasks labeled with  toxicant concentrations (3
                flasks for each concentration)
                5 flasks for chemical analyses
                1 flask for inoculum culture
                1 flask for determination of pH
                1 flask to serve  as a blank when population density is to be
                measured by light or fluorescence spectroscopy
                5 flasks that may be needed  to replace flasks in which salts
                have precipitated
                1 flask for dilution of algal inoculum culture
                5 extra flasks to be used if needed;
                sterilize by heating in  an oven at 60 C for 4 h.
           b. The following method is recommended for preparation of  the
             algal growth medium:
                1. Dissolve all salts, except MgCla-eHgO in  1.5 L of glass-
                distilled or deionized  water in a 2-L volumetric flask.
                2. After dissolution of salts, add the MgCIa 6H2O
                3. After dissolution of MgCIa 6H2O, add 0.5 ml of the PO4",
                NOs",  and SiOa" nutrients; take  to  volume  and determine
                salinity; add 50 ml to culture flasks as above;  sterilize.
           c.  Prepare stock toxicant solution and its dilutions in volumetric
              flasks according to the  instruction  on page 31, wrap masking
              tape around the stoppers and  flask necks to reduce  loss by
              evaporation; store in  the dark  at  4 C in  an  explosion-proof
              refrigerator.
                                    32

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Day 2      a. Examine  each flask  for  presence  of  precipitated  salts  by
             swirling; if precipitate is  present, replace the flask  with  one
             prepared for this purpose.
           b. Mix 7.5 ml of metal solution with 7.5 ml of vitamin solution; filter
             sterilize as  described  on  page  23;  add  0.25  ml  of  the
             metals/vitamins mix to each flask  with  an Eppendorf  pipette
             fitted with a sterile tip; flame  the mouth of the flask before and
             after each addition
           c. Prepare an algal inoculum culture by sterile addition  of 4-5 ml
             of algae from a culture in the  logarithmic phase of growth to the
             flask  prepared on  Day 1; place this culture on a shaker at 60
             excursions min-1  in  the  culture chamber  dedicated only to
             algal  tests; incubate  for 3 days under conditions  identical to
             those of the test.
Day 5      a. Measure pH of the medium in the flask prepared on Day 1; if it
             is  7.9 - 8.3, continue the test; if not, prepare new  medium.
           b. The  inoculum culture  should  be in the early exponential growth
             phase.  Immediately  before  use, dilute to 500 cells  mm-3 by
             addition of growth medium prepared for dilution.  This is done
             by pouring dilution medium into the inoculum  culture  by sterile
             means and estimating population density visually.  A sample is
             taken with a sterile pipette,  added  to  a hemocytometer,  and
             cells  over the four corner squares and  one central square are
             counted on both sides of the  hemocytometer.  At this point, cell
             number should be greater than 500 cells mm-3.  By  careful
             addition of dilution  medium, cell  number can  be  adjusted
             downward to a total of approximately 500  cells  mm-3 On both
             sides of the hemocytometer.
           c. Add  1 ml of diluted algal inoculum culture to all control, carrier
             control, and test flasks with an Eppendorf  pipette fitted  with a
             sterile tip; do not add algae to flasks  prepared for  chemical
             analysis; flame the mouth of each flask before and after each
             addition; swirl the inoculum  culture between  each addition to
             keep the cells in suspension.
           d. Do not add anything more to  the three untreated control flasks.
           e. With  no flame present, add 0.025 ml of earner to media in the
             three carrier  control flasks; add 0.025 ml of carrier to medium
             in one  flask  to serve as  control  when a spectrophotometric
             method is used to estimate population density; swirl each flask
             gently after addition of carrier;  do not flame the mouths of the
             flasks when adding carrier.
           f. Add  each concentration of diluted stock toxicant to the proper
             set of three test flasks and to each  flask prepared for chemical
             analysis; swirl each flask gently after addition of toxicant;  do not
             flame the mouths of the flask when adding toxicant in carrier.
           g. Place the flasks, except  those  prepared for chemical analysis,
             on shakers at 60  excursions  min-1 in the  culture  chamber
             dedicated only to algal tests.
           h. Measure light intensity at the level of the flasks
                                   33

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          i.  Analyze for  the toxicant  in the media prepared for  chemical
             analysis to confirm exposure concentrations.
Day 6     a. Measure light intensity at the level of the flasks
          b. Remove all flasks from the shakers and replace at random to
             insure equal illumination of cultures.
Day 7     a. Measure light intensity at the level of the flasks.
          b. Remove flasks from the culture chamber; estimate population
             density by  cell  counts  or  absorbance  or  fluorescence
             spectroscopy by methods given in Chapter 2 of this manual.
          c. Examine all cultures for presence of abnormal cells; if they are
             present, estimate  their numbers by the method  given on page
             26.
          d. In rangefinding tests, estimate the IC50 and conduct a definitive
             test  with five concentrations  of toxicant  that encompass the
             estimated IC50.
          e. In definitive  tests, calculate the IC50 according to  instructions
             on page 27; calculate the  growth rates of control,  carrier
             control, and test groups as shown on page 28.
          f.  Report results on  the  Reporting  Form For  Single Substance
             Analysis
                                   34

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Reporting Form for Single Substance Analysis
Testing Laboratory
Person in charge
Name of Chemical Compound
Generic
Trademark Soun
Stated Purity (%)
EPA Contract No.
Phone No.
CAS No.
Manufacturer
Date Received
:e

Other Substances in formulation and percentage active ingredient.
Toxicant Stock Solution
Date of preparation
Prepared by:
Method of Chemical analysis
Nominal Concentration Anal}
Purity (%) Anah
Test conditions
Date Begin Date End
pH Salinity


Solvent


/zed Concentration
/zed Purity (%)
Algal Species
Light Intensity:
High Low
Temperature:
High Low Enclose a copy of the Temperature Record
Data recorded in Laboratory Notebook
Number

35

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Test Results
Estimation of Population Density by (Circle):
Cell Counts Optical Density Fluorescence
Range Finder Test Definitive Test
Toxicant Average density
Concentration
1 . Control
2. Carrier
Control
3.
4
5.
6.
7.
8.
Toxicant Average density
Concentration
1 . Control
2. Carrier
Control
3.
4.
5.
6.
7.
8.
IC50 LC50 SC20

36

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Growth Rate (y)
Toxicant
Concentration ja
1 . Control
2. Carrier
Control
3.
4.
5.
6.
7.
8.
Cells of Abnormal
Morphology (%)
Toxicant
Concentration %_
1 . Control
2. Carrier
Control
3.
4.
5.
6.
7.
8.
37

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      4.  Growth Tests with  Liquid Complex Wastes
 Initial growth tests with liquid complex wastes are conducted on unmodified
whole waste. If the  waste inhibits and/or stimulates  algal growth, it may be
desirable to fractionate it to determine if effects are caused by organic or
inorganic constituents. The method outlined below was described by Walsh
and Garnas (1983). It describes analysis of  whole  waste and  fractionation
procedures for use with algal tests (Figure 4).
4.1  Collection of Waste

Samples of  liquid  waste  should  be collected,  shipped, and  stored in glass
vessels with  Teflon  lids  or  in  20-L polyethylene containers,  such  as  the
Cubitamer® (Cole Farmer Industrial Co., Chicago,  IL) or its equivalent. Label
the waste clearly with the name of the site, date, and other data pertinent to
the collection. Give the sample a code number to be used for identification at
all steps in  the testing procedure. The  waste  should  be transported to  the
laboratory immediately after the sample is taken and, when possible, analysis
should be made immediately upon receipt. Do not store the  waste for more
than three days before the  first  test is done.  Samples  should  be  kept at
approximately 4 C during shipment and storage. When received, note color,
odor, and presence of solids, and measure  salinity and pH.

4.2 Filtering of Waste

Waste should not  be filtered, even though particles may  be  present,  except
when it contains algae. When received, examine  it at approximately 100 X
magnification. If algae are present, filter the waste through a  0.45 u.m glass-
fiber filter at no more than  0 5  atm pressure  vacuum.  Pass 1  L of glass-
distilled or deionized  water through the filter before filtering the waste.

4.3 Sterile Techniques

Although the waste is not sterilized, sterile techniques should be used in all
steps of the procedure to avoid addition of  bacteria not found  at the collection
site.

4.4 Estimation of Population  Density

Many  liquid  complex  wastes contain  particulates and  color that preclude
estimation of population density by electronic particle counters and by  light or
fluorescence spectroscopy. If spectroscopic methods are used,  blank media
prepared  from  each  waste  concentration  must be  used to calibrate  the
                                   38

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 Figure 4. Scheme for detecting bioactivity of complex waste and its
 fractions with algal toxicity tests.
                            Receive Waste

                                  I
                     Describe Physical  Properties


                            Salinity, pH

                              Algal Test
                             If Bioactive
         Organic Fraction                    Inorganic Fraction

                 I                                   I
            Algal Test                          Algal Test

           If Bioactive                          If Bioactive
   Base/Neutral  Acid     Particles       Anions             Cations

      I                    II                     '
  Algal Test   Algal Test   Algal Test    Algal Test            Algal Test
instrument  to  zero before cultures exposed to  each concentration  are
analyzed. If the waste is highly colored, absorbance spectroscopy may not be
used. If the waste medium fluoresces at the same emission wavelength as the
algae, fluorescence spectroscopy may not be used.
    In most cases, population density must be estimated by cell counts using
a hemacytometer.
    Examine the cultures microscopically for abnormal cellular morphology.  If
appreciable numbers of abnormal cells are present, estimate their percentage
by differential counts of 100 cells. Do this for all tests on waste.
                                   39

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    Calculate  the average cell  count,  optical  density,  or fluorescence
emission of untreated control  and  all waste cultures. Waste  may  also
stimulate growth,  or it may  stimulate  growth at low concentrations and inhibit
it at higher concentrations.  Figure 5 illustrates  some types of responses that
can be expected.

  Figure 5. Types of responses of unicellular algae to complex liquid
  wastes: A inhibition of growth; B stimulation of growth; C stimulation of
  growth at low concentrations and in inhibition of growth at high
  concentrations.
               
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Control
1
2
3
4
5
% Waste
100
102
105
110
125
160
Waste - Control
-
-
-
10
25
-
Figure 6. Graphical interpolation of the SC20.
               5-1
               4.
            .o
            2
            I
            a
                                     72-h IC50 = 2.9 mg/l
                       20     40     60      80
                          Percentage Inhibition
100
                               41

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4.6 Procedure for Effects of Whole Waste

4.6.7 Preparation of Medium

The  first test should  be done  on  whole waste, filtered only if  algae  are
present, without sterilization. After stirring to achieve homogeneity, remove 2
L and add the  basic  salts  (prepared earlier), PCV, NOs", and Si03~.  Add
the metals and vitamin mixture as for the test with single compounds, but use
a metal working mix without EDTA.
    Store  unused waste in the dark at 4  C because it may be needed for
further tests or for  fractionation  Because waste may change during storage,
subsequent tests should be conducted as soon as possible.
    It is best to  attempt a definitive test on  complex waste immediately in
order to avoid possible effects of storage on toxicity or  growth stimulation.
Dilute the  waste that  contains salts,  nutrients,  metals  (without  EDTA), and
vitamins with similar  growth medium (without EDTA) prepared with glass-
distilled or deionized water. Make dilutions of 0.001, 0.01, 0.1, 1, 5, 10, 25, 50,
and 75% as follows.
    1   2  L of waste = 100%
    2   Add 750 ml of 1  to a 1-L volumetric flask and take to  volume with
        growth medium  = 75%
    3.   Add 500 ml of 1  to a 1-L volumetric flask and take to  volume with
        growth medium  = 50%
    4.   Add  125 ml of 3. to a  250-ml volumetric  flask and take  to volume
        with growth medium  = 25%
    5.   Add  100 ml of 4. to a  250-ml volumetric  flask and take  to volume
        with growth medium  = 10%
    6.   Add  125 ml of 5. to a  250-ml volumetric  flask and take  to volume
        with growth medium  = 5%
    7   Add  50  ml of 6. to a 250-ml volumetric  flask and take  to volume
        with growth medium  = 1 %
    8.   Add  25  ml of 7. to a 250-ml volumetric  flask and take  to volume
        with growth medium  = 0.1%
    9.   Add  25  ml of 8. to a 250-ml volumetric  flask and take  to volume
        with growth medium  = 0.01%
    10.  Add  25  ml of 9. to a 250-ml volumetric  flask and take  to volume
        with growth medium  = 0.001%
 These dilutions were designed to be  made in flasks of standard volume with
a minimum amount of diluted waste  left after addition to test flasks.

    Prepare three  test flasks for each waste concentration by dispensing 50
ml into each of three 125 ml Erlenmeyer flasks Also prepare three  flasks with
growth medium  (without EDTA) as  controls  and an  extra  flask of each
concentration to serve as blanks if spectrophotometric methods  will be used
for estimation of population density

4.6.2   Procedural  Steps

Day 1      a Prepare 3  L  of algal  growth  medium  (page 21) in a  3-L
             Erlenmeyer flask,  deliver  100 ml  into  each  of two  250 ml
                                  42

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             Erlenmeyer flasks and 50 ml  into each of  four  125 ml test
             flasks, place a cotton plug  in the mouth of  each Erlenmeyer
             flask and cap the mouths of the test flasks with stainless steel
             closures; sterilize all flasks with medium  by heating at 60 C for
             4  h;  store the  sterile  medium  in  a  draft- and dust-free
             cabinet.
           b Sterilize 40 125 ml  culture  flasks capped with  stainless steel
             closures,  a 2-L volumetric  flask,  and  a 50-ml dispensing
             pipette by heating at 60 C for 4 h.
Day 2      a. Measure pH  of the  medium in one  of the 50-ml  samples
             prepared on  Day 1;  if the pH is between 7.9 and 8.3 continue
             with the tests, if not,  prepare new medium
           b. Add 0 25  ml of  filter-sterilized  (page  23) metal/vitamin  mix to
             the flask with, 100 ml medium with  an Eppendorf pipette fitted
             with a sterile tip; begin an algal  inoculum  culture in one of them
             by adding 2 - 4  ml of an algal culture in  the  logarithmic phase
             of growth with an Eppendorf pipette fitted with a sterile tip; add
             0 25 ml of the mixture of metals (without EDTA) and vitamins to
             each flask  with 50 ml of  medium prepared yesterday with an
             Eppendorf  pipette fitted  with a sterile  tip, flame the mouth of
             each flask before and after each addition.
    Note. If  algae  are  present  and the waste filtered, absorbance  or
fluorescence methods may be  used to estimate population density  See page
39 for restrictions on use of spectroscopic  methods. When such methods are
used, it is necessary to prepare an  extra flask  with each dilution and undiluted
waste to serve as  blanks.
Day 5      a. With the waste  at room temperature,  add salts and  nutrients
             (Table 1) to 2 L of waste in the sterile volumetric flask. Dissolve
             all salts first except  MgCl26H20, then the MgCl2-6H20; add
             0.5 ml of the P04",  NOa",  and SiCV nutrients;  then  add 10
             ml of filter-sterilized  metals/vitamin  mix (the metals should not
             contain EDTA); take to volume with the remaining waste.
           b. Dilute the waste to which salts and nutrients were added with
             medium prepared on Day 1  according to the method given on
             page 42.
           c. Dispense 50 ml  of undiluted waste and each dilution into each
             of three 125-ml  test flasks with the sterile dispensing  pipette;
             this will include 3 flasks for each of  the 9 dilutions and 3 flasks
             for  undiluted  waste;  label each flask with  identifying  code,
             dilution, and date.
           d Measure the pH  of  undiluted waste and all  dilutions with  the
             portions remaining  after  addition  to  the test flasks;  if
             fluorescence will be used to estimate  population density in
             filtered medium, determine if the waste fluoresces at excitation
             and analysis wavelengths to  be used, if it does, fluorescence
             may not be used to estimate population density
           e Prepare algal inoculum culture by diluting the culture begun on
             Day 2 with  a portion of the  remaining 100  ml  of  medium
                                   43

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             prepared on Day 1, dilute to 500 cells mm-3 by the method on
             page 33
          f  Use  3 of the 125-ml  culture flasks  that contain  50 ml of
             medium as untreated controls
          g. Add 1 ml of the diluted algal inoculum culture to each flask with
             an Eppendorf pipette fitted with a sterile tip, flame the mouth of
             each flask before and after each addition
          h. Place the flasks at random on shakers at 60 excursions mm-1
             in the culture chamber dedicated to algal tests.
          i.  Measure intensity of light at the level of the cultures.
Day 6     a. Measure intensity of light at the level of the cultures.
          b. Remove all flasks from the shakers and replace at random.
Day 7     a. Measure intensity of light at the level of the cultures.
          b  Remove  the algal cultures from the culture chamber  and
             estimate population  density  of  each by  cell counts or by
             absorbance or fluorescence spectroscopy; if the waste is not
             filtered, count the number  of cells as described on page 26;  if
             the waste is filtered, population density  may be estimated by
             cell counts or by absorbance or fluorescence spectroscopy.
          c  If population density is estimated by absorbance, use each
             dilution and the undiluted waste (see note on page 43) to zero
             the instrument  before  measuring absorbance of  cultures at
             comparable dilutions and  undiluted  waste,  or  subtract their
             absorbances from absorbances of comparable test cultures
          d  Calculate  the IC50,  SC20,  or both,  as described  on page 27
             and 40, calculate the average growth rate for control and all
             waste concentration  groups as described on page 28.
          e. Report  results on  the  Reporting Form For  Complex Waste
             Analysis

4.7 Procedures for Effects  of  Inorganic and Organic Fractions

If whole waste is biologically active, and it is desirable to categorize broadly
its toxic or stimulating  components, it may be fractionated  into organic  and
inorganic components  and subfractionated  into anion  and  cation inorganics
and acid and base/neutral extractable organics Also, substances extracted
from particulate matter that is part of the waste may be  tested.
    Tests on  the  fractions and  subfractions obtained  by  the  methods
described here  identify  bioactive  portions of the  waste.  They cannot be
construed to express  toxicity  with great accuracy because  of problems
associated with the  extraction procedures and because of possible effects of
solvents on algal population growth. Further tests may  be required to identify
individual toxic components.

4.7.1 Preparation and Testing of Inorganic and  Organic Fractions

On the day  that the  test on whole waste is placed  in  the  algal growth
chamber, mix the waste well, place 2 L in a glass container, and store in the
dark at approximately 4 C Do not freeze the waste. This portion is to be used
                                   44

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for a test on the whole waste if the first test must be repeated. The remaining
16 L of whole waste will be used for fractionation
    Materials
    1.   142 mm filter holder
    2.   142 mm glass-fiber filter
    3.   Silicon tubing 1/8" id x 1/4" od
    4.   20 L Cubitainer
    5.   Microflow adjustable gear pump
    6.   Disposable syringe with Luer  Lock® (Becton,  Dickenson  &  Co.,
        Rutherford, NJ) tip, 50 ml
    7.   Amberhte XAD-4 resin
    8.   Dowex® (Dow Co., Midland,  Ml)  1-X8 strong base  anion exchange
        resin
    9.   Dowex 50W-X8 strong acid cation exchange  resin,  20  - 50 mesh
    10  20 mm nylon mesh screen
    11  50 Kg scale
XAD-4 Resin  Preparation
    1   Rinse the  resin repeatedly  in an Erlenmeyer  flask with  glass-
        distilled  or deiomzed water until  all salts and fines are removed. Allow
        the remaining resin beads to stand in 2N H2SO4 for  30 mm and  then
        rinse with glass-distilled or deiomzed water.
    2.   Remove impurities by swirling the resin with technical grade acetone
        intermittently for 30 mm, decant,  and remove the remaining  organic
        contaminants by  sequential  solvent extractions with acetone  and
        methanol in a Soxhlet  extractor for 12 h for each solvent.
    3.   Transfer the purified resin with distilled  methanol into an Erlenmeyer
        flask fitted with a ground glass stopper for storage.
    Column
    The column  consists of a  50-ml disposable  syringe loosely  plugged  with
    glass wool and filled with  50 ml (wet  volume)  XAD-4 resin. Use  at least
    20  bed volumes  of glass-distilled  or deionized  water  to displace
    methanol from  the column.  Connect a bored  No. 6  Neoprene®  stopper
    coupled to a 3-cm piece of 8 mm od glass tubing to the  top  of  the
    column. A number of columns can be prepared this way and stored in a
    refrigerator until needed.
    Filter
    Position a glass-fiber filter in the filter  holder and  overlay with  20  pm
    nylon mesh to prevent the  filter from clogging.
    Quality Assurance
    In  conjunction with  the large-volume  extraction method, 1-L  aliquots of
    water sampled before and  after resin treatment should be  extracted
    according to procedures  in  the "Method 625  Base/Neutrals and  Acids"
    (Office of  the  Federal Register, 1986). The fractions obtained from  this
    procedure, i.e., organic base/neutral and acid can be tested for effects on
    algal growth.
    Fractionation System
    1.   Following initial testing of raw effluent,  weigh the Cubitainer and its
        contents to 0 1 Kg, add  a 7 5-cm  Teflon stirring bar  to the container,
        and connect a service faucet to the opening.
                                   45

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    2.   Connect the Cubitamer  to  the  inlet  of the filter  assembly with a
        minimal length of silicon tubing and connect the column to the filter
        exit and to the inlet of the microflow pump with silicon tubing. Direct
        the  exit of the pump into an empty, tared Cubitamer to receive  the
        filtered, extracted  sample  Determine  volume of  the sample
        gravimetrically and store in the dark at approximately 4 C.
    3   Be  sure to stir the  raw effluent in  the  Cubitainer continuously  to
        insure homogeneous distribution of solids, and adjust the pump so
        that the flow through the apparatus is 500 to 1000 ml tr1. Care must
        be  taken  to   avoid  overload  of the  column  with  subsequent
        breakthrough of organics
    4   Following extraction  of organics, remove the Neoprene stopper and
        aspirate the resin by vacuum  to  remove  excess water.  Fit  the
        disposable syringe with an  18 gauge stainless steel needle and elute
        with 150 ml nanograde acetone into a rotary evaporator concentrator
        flask. Concentrate this organic fraction by  vacuum to 25 ml at room
        temperature  and store, tightly capped, m   an explosion-proof
        refrigerator.

4.7.2   Procedural Steps

Day  1     Prepare  XAD-4 resin  and make a  resin column as described on
          page 45.
Day 2     a Prepare 3 L of algal  growth  medium m a 3-L flask (page 24),
             adding  7.5  ml  of each  of the  PO4",  NOa",  and  S\O^'
             solutions; dispense 50 ml into  each of four  125-ml culture
             flasks and cap with stainless steel closures; dispense 100 ml
             into each of  two  250-ml  Erlenmeyer flasks and plug with
             cotton stoppers; plug  the 3-L  flask with a cotton  stopper;
             sterilize all flasks with medium by heating at 60 C for 4 h; store
             in a draft- and dust-free cabinet.
          b. Sterilize  40 125-ml culture flasks capped with stainless steel
             closures, two 2-L   volumetric  flasks,  and  two  50-ml
             dispensing pipettes by heating at 60  C for 4 h.
          c. Pass  the remaining  16 L  of waste through the XAD-4 resin
             column  as described on page 45. Column effluent will contain
             the inorganic  fraction  and,  perhaps,  ionized organics. This
             fraction  will  be called the inorganic fraction, even though, in
             some instances, it may  contain  a  small amount of organic
             material. Store  this  inorganic fraction  in  the  dark  at
             approximately  4 C. The organic fraction is the  material that
             remains  on the XAD-4 resin column.
           d. Extract  the organic fraction  from the resin  with acetone and
             reduce the volume to 25 ml as  described  above; store in  an
             explosion-proof refrigerator.
Day 3      a Measure  pH  of the  medium  in one of the 50-ml  samples
             prepared yesterday, if the  pH is between 7.9 and 8.3 continue
             with the test; if not, prepare new medium.
           b. Add 0.5 ml of filter-sterilized (page 23)  metal/vitamin  mix to
             the flasks with 100 ml medium with an Eppendorf pipette fitted
                                   46

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             with a sterile tip; begin an algal inoculum culture in one of them
             by  adding  4-5 ml  of an  algal culture in  the logarithmic phase
             of growth with an Eppendorf pipette fitted with a sterile tip; add
             0.25 ml of the mix of metals (without EDTA) and  vitamins to
             each of the flasks with 50 ml  of medium  prepared yesterday
             with an Eppendorf pipette fitted with a sterile tip, flame  the
             mouth of each flask before and after each addition
Preparation and Testing of the  Inorganic Fraction
Day 6     a. Prepare  algal  growth  medium  with the  inorganic  column
             effluent 6 with salts as described on page  24, add  the salts to
             approximately 1.5  L of column effluent with continuous stirring
             in the  sterile  2-L volumetric flask; when  the  salts  have
             dissolved,  add 0.5 ml of each of the PCV, N03~, and  SiOs"
             nutrients and  10 ml of the  mixture  of metals  (without EDTA)
             and  vitamins with an Eppendorf pipette fitted with a sterile tip,
             take to volume  with  the inorganic  column  effluent  and mix
             thoroughly; store the  remaining column  effluent in  the dark at
             approximately 4 C, if  fluorescence spectroscopy is to be used
             to estimate algal population  density,  determine if this sample
             fluoresces  at the excitation and analysis wavelengths required
             for  the  test algal  species;  if it does, fluorescence cannot be
             used, if absorbance will be used to estimate population  density,
             determine  if color present  in the fraction is detectable at  the
             wavelength used for the  algal species; if it  is, prepare an extra
             flask, as described in c below, for undiluted  medium and all
             dilutions; use these as blanks  for the zero  spectrophotometer
             settings for comparable  test cultures,  or  subtract  their
             absorbance values from those of comparable test cultures
          b. Add 5 ml of sterile mix of metals (without EDTA) and vitamins
             to each liter of dilution medium prepared on Day 2; dilute  the
             medium prepared  from inorganic column effluent according to
             instructions on page 42.
          c. Dispense 50 ml  of undiluted medium and  each dilution into  3
             sterile test  flasks prepared on Day 2  with the sterile dispensing
             pipette;  this will  include 3 flasks for each of the 9 dilutions and
             3 flasks for undiluted  medium; label  each flask with identifying
             code, dilution, and date.
          d. Measure the pH of undiluted medium prepared  from inorganic
             column  effluent  and all  dilutions with the  portions remaining
             after addition to the test flask.
          e. Prepare an algal inoculum culture by diluting the culture begun
             on Day 3 with a portion of  the remaining  100  ml  of medium
             prepared on Day 2.  Dilute to 500 cells  mm-3  by the  method
             on page  33.
          f.  Use the three flasks with 50 ml medium prepared on Day 2 as
             untreated controls
          g. Add 1 ml of the diluted algal inoculum culture to each flask with
             an Eppendorf pipette fitted with a sterile tip; flame the mouth of
             each flask before and after each addition
                                   47

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          h. Place the  flasks at random on shakers  at 60 excursions min~1
             in the culture chamber dedicated to algal tests.
          i   Measure intensity  of light at the level of the cultures
Day 7     a  Measure intensity  of light at the level of the cultures
          b. Remove all flasks  from the shakers and replace at random.
Day 8     a. Measure intensity  of light at the level of the cultures.
          b. Remove  the algal cultures from the  culture  chamber and
             estimate  population density  of each  by  cell  counts  or by
             absorbance or fluorescence spectroscopy.
          c  If population density is estimated  by  absorbance,  use each
             dilution and  undiluted  medium (see note on page 43) to zero
             the instrument before  measuring absorbance  of cultures  at
             comparable  dilutions and  undiluted  medium,  or subtract their
             absorbances from absorbances of comparable test cultures
          d  Calculate the IC50, SC20, or both, as described on pages 27
             and 40; calculate  the  average growth rate for control and all
             waste concentration groups as described on page 28
          e  Report results on the Reporting Form  For Chemical Fraction
             Analysis
Preparation and Testing of the Organic Fraction
Day 2     a  Prepare  5  L  of  algal  growth  medium  in  a 6-L  flask as
             described on  page 24;  add  1.25  ml of  each of  the  PCV,
             NOa", and S\0^'  solutions, dispense 50  ml into each  of four
             125-ml culture flasks  and cap with stainless steel  closures;
             dispense  100  ml  into each of two  250-ml Erlenmeyer  flasks
             and plug with cotton stoppers, plug  the 3-L flask with a cotton
             stopper; sterilize all flasks with medium by heating  at 60  C for 4
             h;  store in a draft- and dust-free cabinet.
          b. Sterilize 40  125-ml  culture flasks capped with stainless  steel
             closures, two  2-L volumetric flasks, and  a 50-ml dispensing
             pipette by heating at 60 C  for 4 h
Day 3     a. Measure pH of the  medium in one  of the  50-ml  samples
             prepared yesterday; if the pH is between 7.9 and  8 3 continue
             with the test; if not, prepare new medium.
          b  Add  0.5  ml of filter-sterilized metal/vitamin mix (page 23) to
             the flasks with 100 ml of medium with an Eppendorf  pipette
             fitted with a  sterile tip; begin an algal inoculum culture in one of
             them  by adding 4-5 ml of an algal culture in the logarithmic
             phase of growth with an Eppendorf  pipette fitted with a sterile
             tip; add  0.25  of  the  mixture of metals (without EDTA) and
             vitamins to each  flask with 50-ml medium  prepared on Day  2
             with  an Eppendorf  pipette fitted with a  sterile tip;  flame the
             mouth of each flask before and after each addition
Day 6     a  Carefully  add  31  ml  of the acetone solution  of organic
             compounds from the  XAD-4 resin column to approximately
             1.5 L  of growth medium  prepared  on  Day  1  in  a  2-L
             volumetric flask,  add  5 ml  of the mixture of metals (without
             EDTA) and vitamins, bring to volume with growth  medium and
             mix thoroughly.
                                   48

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          b. Dilute  the medium that contains  the  organic extract  as
             described on page 42.
          c. Dispense 50 ml of undiluted  medium and each dilution to each
             of three 125-ml volumetric flasks sterilized on Day  1 with the
             sterile dispensing  pipette; this will include 3 flasks for each of 9
             dilutions  and 3 flasks for undiluted medium; label  each flask
             with identifying code, dilution, and date
          d. Measure the pH of undiluted waste and all dilutions with the
             portions remaining after  addition  to the test flasks;  if fluores-
             cence  is  used  to estimate population  density   in filtered
             medium, determine if the waste fluoresces at excitation and
             analysis wavelengths to be used; if it does, fluorescence may
             not be used to estimate population density.
          e. Prepare an algal inoculum culture by diluting the culture begun
             on  Day  2 with a  portion  of  the remaining  100 ml of medium
             prepared on Day 1, dilute to  500 cells mnv3 by the method  on
             page 33.
          f.  Use 3 of the 125-ml  culture flasks that  contain  50  ml  of
             medium as untreated controls.
          g. Add 1 ml of the diluted algal  inoculum culture to each flask with
             an Eppendorf pipette fitted with a sterile tip; flame the mouth of
             each flask before and after each addition.
          h. Place the flasks at random on shakers at 60 excursions min-1
             in the culture chamber dedicated to algal tests
          i.  Measure intensity of light at the level of the cultures.
Day 7     a. Measure intensity of light at the level of the cultures
          b. Remove all flasks from the shakers and replace at random.
Day 8     a. Measure intensity of light at the level of the cultures.
          b. Remove  the algal  cultures  from  the  culture chamber and
             estimate  population  density  of  each by cell counts  or  by
             absorbance or fluorescence spectroscopy.
          c. If population density is  estimated  by  absorbance,  use  each
             dilution and the undiluted waste (see note on page 43) to zero
             the instrument before  measuring absorbance of cultures  at
             comparable dilutions and undiluted waste, or subtract their
             absorbances from absorbances of comparable test cultures
          d. Calculate the IC50, SC20, or both,  as described on pages  27
             and 40; calculate the average growth rate for control and  all
             fraction concentration groups as described on page 28.

4.8 Procedures for Effects of Inorganic and Organic Subfractions

4.8.1    Inorganic Subfractions

If the inorganic fraction of waste  inhibited or stimulated algal growth, it may  be
desirable to know whether  the  effect  was due  to cations  or anions The
following method may be used for this purpose.
                                   49

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4.8.1.1  Preparation and Testing of the Cation Subtraction

Day 1     a. Prepare  5 L of  algal growth  medium  (page 24)  in  a 6-L
             Erlenmeyer flask; deliver  100 ml  into each  of  two  250-ml
             Erlenmeyer flasks and  50 ml  into each  of four  125-ml test
             flasks; place a  cotton plug in the mouth  of each  Erlenmeyer
             flask and cap the mouths of the test flasks with stainless steel
             closures; sterilize all flasks with medium by heating at 60 C for
             4  h;  store the  sterile  medium  in  a draft-  and  dust-free
             cabinet.
          b Sterilize  40 125-ml culture flasks  capped with stainless steel
             closures,  five  2-L  volumetric   flasks,  and  five  50-ml
             dispensing pipettes by heating at 60 C for 4 h.
Day 2     a Measure pH of  the medium m one  of  the  50-ml  samples
             prepared yesterday, if the pH is between 7.9 and 8.3 continue
             with the test, if not, prepare new medium.
          b. Add 0 5  ml of  filter-sterilized (page 23) metal/vitamin  mix  to
             the flasks with 100 ml medium with an Eppendorf pipette fitted
             with a sterile tip, begin an algal inoculum culture m one of them
             by  adding  4-5 ml of an  algal culture  in the logarithmic phase
             of growth with an Eppendorf pipette fitted with a sterile tip; add
             0.25 ml of the mixture of metals (without EDTA) and vitamins to
             each  flask  with 50 ml of medium  prepared  yesterday with  an
             Eppendorf pipette fitted  with a sterile  tip; flame the mouth  of
             each flask before and  after each  addition.
Day 3-4   a. Prepare the cation subtraction by batch extraction  slowly add 2
             N HCI to 2 L of the inorganic fraction until the pH is less  than 4;
             add 20 g of Dowex 1-X8 strong  base anion exchange resin;
             stir for 24 h; filter the resin from  the sample with the glass fiber
             filter assembly; adjust to pH 7 with 2 N NaOH
          b. Prepare  algal growth  medium  with the cation subfraction.  do
             this by adding  1.5  L  to  a  2-L volumetric  flask, dissolving first
             all  salts  except  MgCIa 6H2O, then the MgCl2.6H2O, and then
             adding 0.5 ml  of the P04", NO3", and S\03' nutrients, then
             add 10  ml of  filter-sterilized metal/vitamin mix (the  metals
             should not contain  EDTA); take to volume with  the  remaining
             waste.
          c. Dilute the cation subfraction  to which salts and nutrients were
             added with medium  prepared  on Day  1  according  to  the
             method given on page 42.
          d. Dispense 50 ml of  undiluted cation medium and each  dilution
             into  each  of  three  125-ml  test flasks with  the  sterile
             dispensing  pipette, this will  include  3 flasks each  for the 9
             dilutions and 3 flasks for undiluted waste; label each flask with
             identifying code, dilution, and date.              •
           e. Measure the pH of undiluted cation medium  and all dilutions
             with the  portions remaining  after  addition to the test flasks; if
             fluorescence will be  used to  estimate  population density in
             filtered medium, determine  if  the waste  fluoresces  at  the
                                    50

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             excitation and  analysis wavelengths  to  be used, if  it does,
             fluorescence may not be used to estimate population density.
Day 5      a  Prepare an algal inoculum culture by diluting the culture begun
             on Day 2 with  a  portion of the  remaining  100 ml of  medium
             prepared on Day 2; dilute to 500 cells mm-3 by the method on
             page 33.
           b. Use  3 of the  125-ml  culture flasks  that  contain  50 ml of
             medium as untreated controls.
           c  Add  1 ml of the diluted algal inoculum culture to each flask  with
             an Eppendorf pipette fitted with a sterile tip; flame  the mouth of
             each flask before and after each addition.
           d  Place the flasks at random on shakers at 60 excursions mirr1
             in the culture chamber dedicated to algal tests
           e. Measure intensity of light at the level of the cultures
Day 6      a  Measure intensity of light at the level of the cultures.
           b  Remove all flasks from the shakers and replace at random.
Day 7      a  Measure intensity of light at the level of the cultures
           b  Remove  the algal  cultures from the  culture  chamber  and
             estimate  population  density  of  each  by  cell  counts or  by
             absorbance or fluorescence spectroscopy.
           c. If population density  is estimated by  absorbance, use each
             dilution and the undiluted waste  (see note on page.43) to zero
             the  instrument before measuring absorbance  of cultures at
             comparable dilutions and  undiluted waste, or subtract their
             absorbances from absorbances of comparable test cultures.
           d  Calculate the IC50, SC20, or both, as described on pages 27
             and  40; calculate the average growth  rate for  control  and all
             cation subfraction concentrations as described on page 28.
           e. Report results on  the Reporting Form For Chemical  Fraction
             Analysis

4.8.1.2    Preparation and Testing of the Anton Subfraction

Day 1      a  Prepare  5  L of algal  growth medium (page 24) in a  6-L
             Erlenmeyer  flask;  deliver 100  ml into each  of  two  250-ml
             Erlenmeyer  flasks and  50 ml into  each  of four  125-ml  test
             flasks,  place a cotton plug in the mouth of each Erlenmeyer
             flask and cap the mouths of the  test flasks  with stainless steel
             closures; sterilize  all flasks with medium by heating at  60 C for
             4  h;  store  the sterile medium in a draft-  and dust-free
             cabinet.
           b. Sterilize 40  125-ml culture flasks capped with stainless steel
             closures by  heating at 60 C for 4 h.
Day 2      a. Measure  pH of the medium  in  one  of the  50-ml  samples
             prepared yesterday, if the pH is  between 7 9 and  8 3 continue
             with  the test; if not, prepare new medium.
           b  Add  0.5  ml of  filter-sterilized (page 23)  metal/vitamin mix to
             the flasks with 100 ml medium with an  Eppendorf  pipette fitted
             with  a sterile tip; begin an algal inoculum culture in one of them
                                   51

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             by adding  4-5 ml  of an algal  culture in the logarithmic phase
             of growth with an Eppendorf pipette fitted with a sterile tip; add
             0.25 ml of the mixture of metals (without EDTA) and vitamins to
             each flask  with 50 ml  of medium  prepared yesterday with an
             Eppendorf  pipette fitted with a sterile tip; flame the mouth of
             each flask before and after each addition.
Day 3-4    a. Prepare the anion subtraction by batch extraction  slowly add 2
             N NaOH to 2 L of the  inorganic fraction until the pH is greater
             than  10; add 20  g of Dowex  50W-X8  strong  acid  cation
             exchange resin (20-50  mesh),  stir for 24 h; filter the resin from
             the sample with the  glass fiber filter assembly, adjust to pH 7
             with  2 N HCI.
           b. Prepare  algal growth medium with the anion  subtraction, add
             1 5 L to a sterile  2-L  volumetric flask, dissolve  first all salts
             except MgCI26H2O; then dissolve  MgCI2-6H20 and add 0.5 ml
             of the P04", NO3",  and SiOa" nutrients,  then add 10 ml of
             filter-sterilized  metal/vitamin mix  (the  metals   should  not
             contain  EDTA),  take to  volume with the remaining waste.
           c  Dilute the anion subtraction to which salts and nutrients were
             added with medium  prepared on  Day 1  according to  the
             method given on page  42.
           d. Dispense 50 ml of undiluted cation  medium and  each dilution
             into  each of three 125-ml test flasks with a sterile dispensing
             pipette, this will include 3 flasks for each of the 9 dilutions and
             3 flasks  for undiluted  waste;  label each flask  with identifying
             code, dilution, and date
           e  Measure the pH of undiluted  waste and all dilutions with  the
             portions remaining after  addition to  the  test flasks, if
             fluorescence is used to estimate population density in filtered
             medium, determine if the waste fluoresces at the excitation and
             analysis wavelengths to be  used, if  it does, fluorescence  may
             not be used to estimate population  density.
Day.5      a. Prepare an algal inoculum culture by diluting the culture begun
             on Day 2 with  a portion of the  remaining 100 ml of medium
             prepared on Day 2; dilute to 500 cells mm-3 by the method on
             page 33.
           b. Use  3  of  the  50-ml  volume  of medium in  125-ml culture
             flasks as untreated controls.
           c. Add 1 ml of the diluted algal inoculum culture to each flask with
             an Eppendorf pipette fitted  with a sterile tip; flame the mouth of
             each flask before and after each addition.
           d  Place the flasks at random  on shakers at 60 excursions  min-1
             in the culture chamber dedicated to algal tests
           e. Measure intensity of light at the level of the cultures.
Day 6      a  Measure intensity of light at the level of the cultures
           b  Remove all flasks from the shakers and replace at random.
Day 7      a. Measure intensity of light at the level of the cultures
                                   52

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           b. Remove the algal  cultures  from the  culture chamber and
             estimate population density  of each  by  cell counts  or by
             absorbance or fluorescence spectroscopy.
           c. If  population density is  estimated  by  absorbance,  use each
             dilution and the undiluted waste (see note on page 43) to zero
             the instrument before measuring absorbance of cultures  at
             comparable dilutions and undiluted waste,  or  subtract their
             absorbances from absorbances of comparable test cultures.
           d. Calculate the IC50, SC20, or both,  as  described  on  pages 27
             and 40;  calculate the average  growth  rate for control and all
             anion subtraction  concentrations as described on page 28.
           e. Report  results on the  Reporting Form  For Chemical Fraction
             Analysis

4.8.2   Organic Subtractions

If the organic fraction  of waste inhibited or stimulated algal growth,  it may be
desirable  to  know  whether the  effect was  due  to acid or  base/neutral
extractable organics.  The extraction method  is described in "Method 625
Base/ Neutrals  and Acids,"  published  in the  000*6  of  Federal Regulations
(Office of the Federal  Register,  1986). It is best for the lexicologist who works
with these  subtractions  to  consult  that publication  for details of the
subfractionation  steps  and instructions for preparation  of the  base/neutrals
and acid subtractions of the organic fraction.

4.8.2.1  Preparation and Testing of the Subtractions

Day 1      a. For each subtraction prepare 5 L of algal growth medium (page
             24) in a 6-L Erlenmeyer  flask; deliver 100 ml into each  of two
             250-ml  Erlenmeyer flasks and 50 ml into  each of four 125-ml
             test  flasks; place  a  cotton  plug  in  the  mouth   of  each
             Erlenmeyer flask and cap the  mouth  of  each test  flask with
             stainless steel  closures;  sterilize all  flasks  with medium by
             heating at  60  C  for 4  h, store the  sterile  medium in a  draft-
             and dust-free cabinet.
           b. Sterilize  40 125-ml culture flasks capped  with stainless steel
             closures by heating at 60 C for 4 h.
Day 2      a. Measure pH of  the medium in one  of  the  50-ml   samples
             prepared yesterday, if the pH is between 7.9 and 8 3 continue
             with the test; if not, prepare new medium.
           b  Add 0.5 ml of  filter-sterilized  (page 23) metal/vitamin mix to
             the flasks with 100 ml medium with  an  Eppendorf pipette fitted
             with a sterile tip, begin an algal inoculum culture in one of them
             by adding  4-5 ml of an  algal culture in the logarithmic  phase
             of growth with an  Eppendorf pipette fitted with a sterile tip; add
             0 25 ml of the mixture of  metals (without EDTA) and vitamins to
             each of the flasks with 50 ml of medium prepared  yesterday
             with an  Eppendorf  pipette fitted with  a sterile tip,  flame the
             mouth of each flask before and after each addition.
           c. Add  3.1 ml  of the organic  fraction to  2 L of distilled or
             deionized water and extract according to instructions given for
                                   53

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             separatory funnel  extraction in "Method  625-Base/Neutrals
             and Acids" of the Code of Federal Regulations.  This will yield
             two organic subtractions  base/neutral  and acid in  methylene
             chloride. Before testing, exchange  the methylene chloride with
             dimethyl sulfoxide, which  is less toxic  to algae.  Take the
             volume to 2 ml and store as instructed in Method 625.
          d. The  following instructions  (Day 6) describe testing with  both
             extracts. Testing may be done on each at the same or different
             times.
Day 6     a. Add 2  ml of the base/neutrals or acids extract to  approximately
             1.5 L of algal growth medium  prepared on Day 1 in  a sterile
             2-L volumetric flask;  add  5 ml of the mix of metals (without
             EDTA) and vitamins; bring to volume with growth medium and
             mix thoroughly.
          b Dilute  the  medium that contains  the  organic  subtraction as
             described on  page 42.
          c Dispense 50  ml of undiluted  medium and each dilution into
             each  of three  125-ml test flasks with a  sterile  dispensing
             pipette, this will include 3  flasks for each of 9 dilutions and 3
             flasks  for undiluted  waste; label  each flask  with  identifying
             code, dilution, and date.
          d Measure the  pH of undiluted medium  and all dilutions with the
             portions  remaining  after addition  to   the  test flask;  if
             fluorescence  is used  to estimate population density in filtered
             medium, determine  if the waste fluoresces at  excitation and
             analysis wavelengths  to be used; if it does, fluorescence may
             not be used to estimate population  density.
          e Prepare an algal inoculum culture by diluting the culture begun
             on Day 2 with a portion of the remaining  100 ml of medium
             prepared on  Day 2; dilute  to 500 cells mm-3 by the  method on
             page 33.
          f. Use  3  of  the  125-ml culture  flasks  that  contain  50  ml  of
             medium as untreated  controls
          g. Add 1  ml of the diluted algal inoculum  culture to each flask with
             an Eppendorf pipette  fitted with a sterile tip; flame the mouth of
             each flask before and after each addition.
          h Place the flasks at random on  shakers at 60 excursions  min'1
             in the culture chamber dedicated to algal tests.
          i. Measure intensity of light at the level of the  cultures.
Day 7     a. Measure intensity of light at the level of the cultures.
          b Remove all flasks from the shakers and replace at random.
Day 8     a. Measure intensity of light at the level of the cultures
          b. Remove the  algal cultures from  the culture  chamber and
             estimate  population  density of each  by  cell  counts  or by
             absorbance or fluorescence spectroscopy.
          c. If  population  density is estimated by absorbance, use  each
             dilution and the undiluted  waste (see note  on page  43) to zero
             the  instrument before  measuring absorbance  of  cultures  at
                                    54

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             comparable dilutions and  undiluted waste,  or subtract  their
             absorbances from absorbances of comparable test cultures.
           d. Calculate the IC50, SC20, or both, as described on pages  27
             and  40; calculate the average growth rate for control and  all
             subtraction concentrations as described on page 28.
           e. Report results on the Reporting Form For Chemical Fraction
             Analysis.

4.9 Procedures for Extraction and Testing of  Particles

The following procedure may be used to determine if organic materials that
can be extracted from waste particulate matter are toxic.

4.9.1   Extraction of Organics

    1.   Remove the glass fiber filter and nylon screen from the filter holder;
        cut into pieces;  place  in  a 150-ml  Corex® (Corning Glass Works,
        Corning, NY) bottle.
    2.   Extract the filter pieces 3 times with 50 ml nanograde acetone  using
        a Branson Sonic Probe for  5 min with each extraction.
    3.   Centrifuge the extract at 5000 RPM.
    4.   Concentrate the  combined acetone  extracts  by  vacuum  at  room
        temperature to 25 ml.

4.9.2   Testing of Extract

    1.   The extract contains organics from the particulate  matter in 16 L of
        waste
    2.   Test this extract with  the  method "Preparation and Testing  of the
        Organic Fraction"  page 48.

4.10    References

Office of the Federal Register. 1986. Method 625-base/neutrals and  acids.
    pp. 442-469. Code of  Federal Regulations, 40 CFR  104.1, Revised July
    1, 1986, U.S. Government Printing Office, Washington, DC.
Walsh, G.E. and R L. Garnas. 1983.  Determination of bioactivity of chemical
    fractions  of liquid  wastes using freshwater and  saltwater algae and
    crustaceans. Environ. Sci. Technol. 17: 180-182.
                                  55

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Complex Waste Analysis Reporting Form
Testing Laboratory
Person in charge
Origin of Waste
Name of Site
Type of Industry
Sample Collected By
Method of Collection
Method of Transport
Log No.
EPA Contract No.
Phone No.
Address
Date Collected
Date Received
Time of Transport

Color pH Salinity Odor Solids
Other Applicable Characteristics
Test Conditions
Date Begin Date End Algal Species
Light Intensity: High
Low

Temperature:
High Low Enclose copy of Temperature Record
Data recorded in Laboratory Notebook Number
56

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Test Re
Estimation of Population Density
Cell Counts Optical De
First Test
Waste Cone Average density
(%)
1 . Control
2.
3.
4.
5.
6.
7
8.
9.
10.
11.
suits
by (Circle):
snsity Fluorescence
Second Test (If Necessary)
Waste Cone Average density
(%)
i. Control
2.
3.
4.
5.
6.





IC50 LC50 SC20

57

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           Chemical Fraction Analysis Reporting Form
Test Conditions

      Date Begin
     Date End
        Algal Species
Light Intensity: High
              Low
Temperature:
High	Low
Data recorded in Laboratory Notebook Number
Test Results, Fractions

Estimation of Population Density by (Circle):
       Cell Counts     Optical Density     Fluorescence


 Fraction
  Range Finder Test
             Definitive Test
  % Original
      Cone.
Average
Density
% Original
    Cone.
Average
Density
 1. Control
2.
3.
 5.
 1C50
                                1. Control
                               2.
     LC50
                                             SC20
                              58

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Growth Rate (p)
Waste
Concentration (%) y
1 . Control
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Cells of Abnormal
Morphology
Waste
Concentration (%) %
1 Control
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
59

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                   5.  Bioaccumulation  Test

It may  be important  to know  if  algae accumulate  a compound.  This  is
determined by exposure of a population for 24 h, with subsequent chemical
analysis.
    1.   Dispense 1  L of algal growth medium into six 2.8-L Fernbach flasks,
        seal with a foam plug or cotton stopper, and sterilize in an oven at 60
        C for 4 h.
    2.   Add  100  ml of an algal stock culture in the exponential phase  of
        growth to the flasks and incubate in a growth chamber for five days
        Continuous light at 100-120 u.E nv2 sec~1  should  be  supplied  at
        20 C. Swirl  the flasks twice each day to maintain gaseous exchange
        between atmosphere and growth medium
    3.   On Day 5, add toxicant  at the highest concentration that does not kill
        algae (see  Enumeration of  Dead Cells Section) to five  flasks, and
        return the cultures to the growth chamber for 24 h.
    4.   After  24  h exposure,  centrifuge the  cultures  at 5000 rpm and
        combine all treated algae by resuspension in fresh medium  (without
        toxicant);  add  them  to a previously weighed  centrifuge tube and
        centrifuge again.
    5.   Weigh the  tube with algae  and  subtract  the weight of  the  tube  to
        determine the weight of algae
    6.   Analyze for toxicant concentration  in algae from the  control and
        treated flasks and calculate  uptake as weight  of toxicant per
        milligram of wet cells versus weight of toxicant per  milliliter of growth
        medium. Calculate the concentration factor:
           Concentration  Factor = toxicant concentration in  algae
                               toxicant concentration in water
    7.   If concentration of toxicant per milligram of dry algae is desired
        a.   Dry a filter to constant weight at  110 C.
        b.   Collect a known wet weight  of algal cells suspended in growth
            medium on the filter by very gentle vacuum
        c.   Dry again to constant weight at  110  C and weigh to the nearest
            0.1 mg
        d   Subtract the weight of the  filter from the weight of the filter with
            algae for dry algal weight.
        e.   Calculate the concentration factor as described above.
        f.   Report results on the Bioaccumulation Studies  Reporting Form.
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NOTE:This method cannot be used if the toxicant is volatile at 110 C  There is
a small error in estimation of dry weight of algae by the above method

    Some of the salt from the growth medium will be present on the cells and
filter after drying. This is small in relation to algal weight and may be ignored
in this test.
                         Test Results
   Toxicant Concentration in Test


   Nominal                         Analyzed
  Bioconcentration
                       Toxicant         Toxicant        Cone, in
                    Concentration    Concentration      Algae/
                        Algae          Medium        Cone, in
                                                       Medium
   1. Control
   2. Treated
                                 61

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Bioaccumulation Studies Reporting Form
Testing Laboratory
Person in charge
Name of Compound
Chemical
Generic
Trademark
EPA Contract Number
Phone Number
CAS No.
Manufacturer
Date Received
Source
Stated Purity (%)
Other Substances in Formulation and Percentage Active Ingredient
Toxicant Stock Solution
Date of Preparation
Solvent
Prepared by
Method of Chemical Analysis
Nominal Concentration
Purity (%)
Test Conditions
Date Begin
Algal Species pH
Light Intensity: High
Analyzed Concentration
Analyzed
Date End
Salinity
Low
Temperature:
High Low Enclose copy of Temperature Record
Data recorded in Laboratory Notebook Number
62

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         6.  Enumeration of  Living and Dead Cells

The method used here for detection  and enumeration of dead algal cells was
described by Crippen and Perrier (1974); Reynolds et al. (1978)  and Walsh
(1983)  used it  to  detect  effects  of toxicants  on marine  unicellular algae.
Alexander and Wilkinson (1987) showed  that toxicants may affect  the pattern
of staining
    1    Prepare a  1%  (w/v) solution  of the  acidic mono-azo dye,  Evans
        blue, by dissolving 1 g of the dye in 100 ml of algal growth medium
    2.   Prepare an algal  test with Skeletonema  costatum as described for
        single substances but do not  add toxicant After 48 h, remove  the
        algal cultures from the growth chamber and add toxicant and solvent
        carrier as for the test with single substances. Return the  cultures to
        the growth chamber  and incubate for 24 h.
    3.   After 24-h  exposure, centrifuge the culture gently and  resuspend
        the cells  in a  selected  volume of uncontammated  medium.
        Centrifugation  should not disrupt  cells,  time  and  speed  of
        centrifugation must be determined  by trial and error. Dispense 10 ml
        of the suspension into a test tube.
    4.   Add  0.5 ml  of the  Evans  blue  solution to  the  10  ml  of  algal
        suspension and wait 30 mm
    5.   After 30 mm, swirl the suspension to distribute the cells evenly in the
        medium and, with a pipette, fill  both sides of hemacytometer.  Dead
        cells will be colored  blue.
    6.   Make a differential count  of a total of  100 living and dead cells at
        400  x  magnification over  the grids on  each  side  of  the
        hemacytometer This can  be done by using a hand talley  with four
        channels, designating one for  living cells and one for  dead cells on
        each side of the hemacytometer
    7.   Add the living and dead cell counts of each flask and calculate  the
        percentage of dead cells for the triplicate control, carrier control, and
        toxicant concentrations.
    8.   Calculate the LC50  by  straight-line graphical interpolation as shown
        in  Fig.  3. Plot concentration on  the y axis and  percentage dead on
        the x axis.
    9.   Report counts of living and dead cells in  control, carrier control, and
        all toxicant  concentrations,  giving counts on  each  of  the three
        cultures in each of the groups,  their averages, and the LC50.
                                   63

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6.1  References

Alexander, L M and M Wilkinson. 1987. A protocol for the validation of vital
    and mortal stains. Bot Mar. 30: 109-113.
Cnppen,  R.W  and J L Perrier  1974  The use of neutral red and Evans blue
for live-dead determinations of marine plankton. Stain Technol. 49:  97-104.
Reynolds, A E , G.B  Mackiernan, and  S.D. Van Valkenburg. 1978. Vital and
    mortal  staining  of algae in the presence of chlorine-produced oxidents.
    Estuaries  1:  192-196.
Walsh, G E. 1983. Cell death and inhibition of population growth of marine
    unicellular algae by pesticides. Aquat. Toxicol.  3' 209-214
                             .Government Printing Office: 1988 — 548-158/67090
                                    64

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