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-------
TABLE E.+.  SIGNIFICANT LEVELS OF 8: VALUES OF 8 (LARGE TYPE
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-------
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                                 140

-------
TABLE E.4,  SIGNIFICANT LEVELS OF 8: VALUES OF 3 (LARGE TYPE
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-------
TABLE 6**V:." SIGNIFICANT LEVELS OF 8: VALUES OF 3 (LARSE TYPE
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                                     142

-------
TABLE E.4.  SIGNIFICANT LEVELS OF B: VALUES OF 3  (LARGE TYPE
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-------
                                APPENDIX  F

                             PROSIT ANALYSIS^


1. -PROSIT ANALYSIS OF FATHEAD MINNOW EMBRYO-LARVAL DATA

1.1  This program calculates the LCI  value and associated 95* confidence
limits using Probit Analysis.  The program, written in FORTRAN PLUS IV
v.3,  was adapted by James Dryer, EMSL-Cincinnati, from a program obtained
from Ors. Wesley Birge and Jeffrey Slack, Graduate Center for Toxicology,
University of Kentucky, Lexington.

1.2  The program runs on the Digital  Equipment Corporation, PDP-11/70 -
computer under IAS version 3.1.  Machine readable copies of the program
and assistance in running it can be obtained by contacting James Dryer,
EMSL-Cincinnati Newtown Facility (FTS 778-8350; comm'l 513-527-8350).

1.3  Sample Data Input and Output from the Computer Program

1.3.1  The data input process and the output provided by the computer
program are illustrated with a set of mortality data from a fathead
minnow embryo-larval survival and teratogen.icity test.

    The program begins with a request for the following information:

    1. The number of concentrations.
    2. The number of test organisms exposured in the control.
    3. The number of test organisms that died in the control.

    The program then requests information on each toxicant concentration:

    1. The concentration value.
    2. The total number that died at each toxicant concentration.
    3. The number of test organisms exposed at each toxicant
       concentration.

    Probit statistics are then  listed for the analysis, including a table
which provides the LCI value and confidence limits.
 1Prepared by James  Dryer, Aquatic  Biology Section, EMSL-Cincinnati
 Newtown Facility, U.  S. Environmental Protection Agency, 3411 Church.
 Street, Newtown, Ohio
                                     144

-------
1.3.2  Sa«pl« Oita Input and Output from the Computer Program for Probit
Analysis of Fathead Minnow Embryo-larval Data
       PROBIT ANALYSIS***MAXIMNM LIKELIHOOD SOLUTION

            USED FOR CALCULATING LCI S»  . ,. .  LC99 S

        MAXIMUM NUMBER OF POINTS IS 20.

     NUMBER OF CONCENTRATIONS = 5
     '•CONTROL SAMPLE SIZE » 100.
     NUMBER OF HEAD IN THE CONTROL GROUP17.
       8ESIN INPUTTING OF DATA WITH LOWFST  CONCENTRATION

     CONCENTRATION - 3.
     NUMBER RESPONDING (BEAD) = 14.
     NUMBER TREATED =* 100.

     CONCENTRATION =5.
     NUMBER RESPONDING (HEAD) = 1/5.
     NUMBER TREATED = 102.

     CONCENTRATION = 7.
     NUMBER RESPONDING (DEAD) = 35.
     NUMBER TREATED - 100.

     CONCENTRATION =11.
     NUMBER RESPONDING (HEAD) = 72.
     NUMBER TREATED =99.  '

     CONCENTRATION = 1<5.
     NUMBER RESPONDING (DEAD) = 99.
     NUMBER  TREATED = 99.

     INPUT  CONCENTRATION SCALE IS  TRANSFORMED TO LOG(10)
                               145

-------
1.3.2  Sample;data  Input and output from the  computer program (continued),
      LOS
 CONCENTRATION SAMPLE
   0.4771
   0.8451
   1.0414
   1.2041

  CONTROL
10O.
102.
100.
 99.
 99.

100.
  PROSIT   TABLE..

OBSERVED      EXPECTED

     14.  .
     35.
     72.
     99.

     17.
                                       DEVIATION   PROBABILITY
15.38.
17.79
31.32
74.43
9A.37

15.57
-1.58
-1.79
 3.48
-4.45
 2.43

 1.43
0.1558
0.1744
0.3132
0.7720
0.9734

0.1557
 THP CONSTANTS USED  IN THIS PROBLEM WERE5

      HETEROGENEITY  FACTOR »    1.5884
          NUMBER OF  POINTS -    5
         DEGREES OF FREEDOM -    3
                   DEVIATE *    1.9400
                          8 >    0.0515
 THE TOTAL  NUMBER OF CYCLES-    2.

 THE STATISTICS ARE}
                   '   AVG Y         5.3497
                  . .  ..AVG X         1.0059 "
                      AVG T         1.4983
          NATURAL MORTALITY         0.1557
                      SLOPE         9.0354
                 INTERCEPT        -2.7134
               CHI SQUARED         4.7458
                           S£
                           SE
                         0.0229
                         0.93O4
      POINT      CONCENTRATION


   LCI                 4.4817
                        LOWER                UPPER
                          9SZ CONFIDENCE LIMITS
                          3.4430
                                             5.5047
  NOTE:IF THE LCI is ABOVE/BELOW THE HIGHEST/LOWEST CONCEN-
  TRATION  TESTED* EXTREME CAUTION  SHOULD BE EXERCISED IN
  REGARD TO  USING SUCH VALUE BECAUSE IT LIES  OUTSIDE THE
  KNOWN RANGE A*0 IS ONLY AN EXTRAPOLATED ESTIMATED  VALUE.
  SIMILAR  CAUTIONS  SHOULD  ALSO BE USED IN REGARD TO THE
  UPPER  AND  LOUER 9SZ CONFIDENCE LIMITS FOR LIKE REASONS.
  FOR FURTHER CLARIFICATION. PLEASE CONSULT YOUR QUALIFIED
  STATISTIC!***.     .
                                       146

-------
1.3..3  Listing of Computer  Program for Probit  Analysis  of Fathead Minnow
     Embryo-larval  Data
               SGSZCXF SSffi* (A-a.O-Z)
               nQEBiar JMT(U) ,S3(20) ,aW3ES(20) ,SWSI(20) ,VEE(13)
               ansfflzar acpz(20) ^993(20) ,^999(20) ,214(20) ,ros(is)
                         BHS>(20),(2132(18),
                         X(20),»(20)1
         c
         c
         c
         c
         c
    IHfUHTlH OF(1) ,02(1)
       OP,OI/0.01,2.6737/

           -**! VMUES 9SCB&D.

 HOTS;  THIS   VERSION   WRITTBK   9/16/83

   CMDk TOS,CS1SO/12.70«,*.3CO,3.132, 2.776, 2.571,
  * 2.447,2.353,2.306,2.262,2.228,2.201,2.179,2.160,
  * 2.143,2.131,2.120,2.110,2.101,3.341,3.391,7.313,
  * 9.483,11.07,12.592,14.067,13.307,15.913,13.307,
  * 13. 673,21.026,22.362, 23. 633,24.99«,26.a9«r27.5a7,
  * 23.3fi9/
           100 TDK*,
   T5SB*,
   TXEC*/
   T2ES 2      	
 2 Pdaflfff' 2CHSES OF
   ACCSPI 3,N
 3 KSSOI(I2)
   THE 4      	
 4 IQEKXCC Gd/iHGLi SSMHE
10
                               WMSCR OF KOftS IS 20.
                                             ',$)
                               TO 1
             1TOB 3
             5 BJgag (' HOMEEaOFCEAO IK OB CCMIEGL GBOOF « ',$)
               03 ID 200
           192 SO ID 9999
           200 HCG- 1
               OO TO 260
           230 03 250 J - 1,
               H(J) --
           230 X(J) " ESOS10WJ))
                           ,280,270
                    JB 2
           280 ICZCI^-1
               lMf-2
           270
               GOTO 290
           280
               BIGCXI.CO
                                            147   .

-------
1.3.3   Ltstlnig of Program for  Probit Analysis of Fathead Minnow
        Bnbryo-larval Data (Continued)
           290 00 TO (300,320), XCOS
           300 TSB*, '  '   _  _
              TOE*, '  "o uiujt nocniHs 07 DMA HUH THE IOOST
              03 330 J-1,H
              TZ8B 313,
           311 B3WKTC OSHCnnHMnar * ',$}
              £0399 312,X((oasL.zz.o  ) .OR. (icrct.Gz.of )   0010320
              CEOKKOOO
              03 313 I-1,H
                                        S3 TO 313
           315 "*"''"'*
              rF(nQc«.aa.o)  GO TO 320
           320 IPCOID.IX'.l) 03 TO 230
              DO 400 I-l.K
            6   	
              IP (ICZtt) 350,390,390
           350 3?(SMtt»(D .12.0.00) GO TO 330
              13"(afltt3?(I) .GS.1.DO) O3 TO 340
              03 TO 380
           330 SMttS(I)«.
              03 TO 380
           340 SMOS(D-.9999EO
           330 <
            . 03 TO 400
           3se>r-	
           400 <
         C
         C
         C
         c
              S»0>O.DO
              snoaiM.oo
              SWOOO.DO
                                          148

-------

-------
1.3.3  Listing of  Program for Probit  Analysis  of Fathead Minnow
        Embryo-larval Data (Continued)
                SMflM.GO
             .  oo 470 X-1,H
                S>OSSZ(X) -5.BO
                nr
                GO ID 431
            430 »•( (0.000043063aPO**gH}.000276SS72PO) *»M. 000332014300) *Mft-O.Q09
               A&-.5DO-.5IX/ ( ( (AI*AHK 042282012300) **». 070S230784CO) *A»1.DO) *•!
               16            _
            431 BBSP(I)».3DO+CSIGS(AI,£D)
            440
               !?( (BES?(Z) .ZZ.1.00) ~AMD. (DRBS(H5) .12.13.00) )  GO TO 441
               WM^J.OO                       .   •  '
               00 TO 442                     -
            441
            442
               HfflDWOCK(I)
               sar -
                3U&&K&BIHX
                I? (ZCZCO 470,450,450
            450
            460
            470 CCNCfflOS
                IT(S»l.aj.O.DO)  CD TO 520
            471
&((atOX.ZQ.O).CR.(S»OGr.SQ.O)} GO TO 520
EHEW>€f*Qa/SltCCC
SB-OKEX

IFOflttO 471,472,472



                            149       :-

-------
1.3.3  Listing of  Program for Probit Analysis  of Fathead Minnow
        Efflbryo-larval Data (Continued)
               0*5.03
               CZ2*>0«00
           472 If (1CXCL) 480,500,500
           490 00 490 1-1,21
           490
               GO TO 320
           500 XF(satq 520,510,510
           510
               GUI-LOO/ (swcc-saonysanr*swca)
           502
           520 00 530
           530
               g(TgSr)540,550,550
           540 fSSX^^CEStS
           550 IF(XCSe&-100) 560,580,580

           561 IF(TZ3T.IZ.CQ001EO)   GO TO 610
               GO TO 570
           565 X?((TE5T.XZ..01DO).aR.(CaBS(BNE»-B8).£r..OOSQO)) GO TO 610
           570 &BKSSI
               GO TO 320
           580
           590
           600 BSSBXC49H 100 CK32S HAVE BEEN CCMETEIED. 3(100) - 3(99) -,F14.7)
         C
         C              	     	     	
         C     rXTCTTy* r~"'*^i 2HD •'•"«'• FOR »«i-iTMiS%i'.i-'iV-
         c
           610 D-3
               X7(2CaS3*Q) GO TD 320
               zr ( sso.flR.nrreoxK)) GO TO 650
           649 GO TO 820
           650 W03B(5,660) XSQ
                          ____    _        _ ^^^
           640 JCBHK (47H 
-------
1.3.3  'Ltsffiiif o? Program  for  Probit Analysis of Fathead Minnow
                          Data  (Continued)
          C
          C    SB? OP C9SS9NIS AHD ULMHUS. S393XSCCC3.
                rFdCRIrfSM?) 830,330,330
            330 WH2{5,340)
            340  £CRKC(  26H NOdQUi'ICAOT HBSBESSSCN/)
            350
                DO 980
                g(CBKCT .Z2.0.00) 00 TO 360
                g(QB8Bf (CT) .CS.1.00J 00 TO 370
                GO ID 920
            860
            _ GO TO 920
            370
            920
                      '
                TOB*,'  •
    TBB*,'
    XFCHOG.aa.2)
929 B3RaZ(fiC,3HC
    W03S(5, 330)
   1  ggg(J) ^j.,^
930 futouJCUC, l.lff ,tt!LiLMiliAlIIlJT,I^,SHSflMRZ>gyf
   ID ,7X,?aa
                                                 PRO BIT  TA-BI,a«
                                 oa ro 940
                            _
                T3Q3B(S , 933) GZISIi, COO, "SBSX, 3,5X£G
               1
            935
                                                      _
            950 PCBMKT(4iaOIHB OONSBanS- IMfel) IN '1H13 ESOHtaC
                «O3Z(5f360)HSr
            960 ler^>nnt(*y, J JUUMI ym iJi.'Mgr'ffy FACTOR »,J9.4)
                WaZE(5,970)H
            970 !aWKP(iar,19HHCKBCEl 0? FOZHS - ,13)
                !XQ!B(5,980)S
            980 FOHJKTO^iaBnEXSEES OF ESEED3C - ,13)
            990 B3WW(13X,3H3E7iaiE -,£9.4)
             * ~ «B3B(5,1000)G
           uoa
                      -' •- -   •
           wia KsaKctsaa IBE rorai. NUMBER or cxci2s-,i4,iH.)
            940 nrd-GT.O) WRECE(5,94S)
            945 ZCROS(3aO,48Xr '*-£XI®Cm3 I2SS ISftH 5 '/49X, <**>£S&CTED tCRS
           1020 FOraai(22B3IHE S
                                              151

-------
1.3.3  Listing of  Program for Probit Analysis  of  Fathead Minnow
        Embryo-larval  Data (Continued)
           1030 icaag(2af7gBic T -,212.4)
                mis(5,io40)xsxac
           1040 ICSKM(213C,7HXVG X - ,112.4)
           10SO KHflg(23X,7HM?S T - ,512.4)
                HQ2E(5,1060)BXBe,SEC
           loco IOWMOX, isaoacsxL icRjacnz -,512.4, 4x,4HSB - ,Pio.4)
                HBnE(5,1070)BKar,SEB
           1070 KR9S(21X,7E5USS - ,F12.4,4iC,4BSB -,510.4)
                W03S(5,10SO)A.
           1080 IOH«C(I7X,llSniTEBC2E!? -,F12.4)
                303E(5,1090)3SQ
           1090
                                                      _
           1095 FCE39£C(  'Q*G3£ aquflRED IS CTQOjTQHr.  ^i-i-i.nnJMM||i|il|y E&JIUK IS
               1 HOT I KID.  CSS
                TXH*,'
               1
           iioo
          c     _
               13025(5,387)
            987 rcswxrr          •                              95*
                        _
                OLSUU1Z J;lHX.'LATi
                                 GO ID 1150
           U10
               GO TO (1130,1120)
           1120
           1130 I?(HI.GI.X1*(II))A999(J)«3P(1)*100
           1140 HS«XC(S  IC1,4X,1    ',FlS.4,5XfFlS.4r3X,?16.4)
               GO TO nso
           1150 GO TO ,(1170,1160) ,HSS
           1160 aMSO?(2.30253SOa*EH)
           1170 wnas(5,nso)  CP(D*IOO.,EH
           LUM ICKBOrC tC',23.0,iaC,nS.4,aX, •  aSCALCUL
           lisa Tgs», '
               1— - '
               ins*,1 •
               BOB*, ' •                               _   _
               T&fi*, 'NOIKIF *Pffl! Tm XS ABCVE/EEICW THE HKjHEST/ICSffigr
               'i'iltB*, "CaZECM  'in.vivj>f EOEEME cai/riLH  *iHniJIJ) BE EXERCISED DT
               T2HE*, 'BSSKEO TO  US2HB ^.^^ VMDE HECKDSE TT TilTB  W»JITI 1 1 f. TBS*
               TXPE*, "SNCMJ SSNCSB AND IS CttlX AH SCTRAPOraiCED SSTIMRISO  VAZDE. '
                            n  CBDnCKS  aCULD  AtSO BE USED IH REGSVBD TO THE'
                             MO  ICWER 95* CCNFUENCS TTHTT3 FOR USE SEASONS. '
                                             152

-------
1.3.3   Listing of Progran for  Probit Analysis  of Fathead Minnow
        Bafcrya-larval Data (Continued)
              TSFE*, 'SCR gOigSgt QiSSKXCSSS, EUaSB tlHSU'luT YQCR
                   ,
              T2BB*,1 •
           •  HRnZ<3,9991)
          9991 FCEHK
          9999 STOP
              HMD	
                  i IHK'I'll H iMJfiill*8vii«jitJ
                                         153

-------
2.  PROBIT ANALYSIS OF ALGAL GROWTH TEST DATA

2.1  This prograa calculates the EC! value and associated 95% confidence
limits using Probit Analysis.  The program, written in FORTRAN PLUS IV
v,3, was adapted by James Dryer, EMSL-Cincinnati, from a program obtained
from Ors. Wesley Birge and Jeffrey Black, Graduate Center for Toxicology,
University_of Kentucky, Lexington.

2.2  The program runs on the Digital Equipment Corporation, POP-11/70
computer under IAS version 3.1.  Machine readable copies of the program
and assistance in running it can be obtained by contacting James Dryer,
EMSL-Cincinnati Nevrtown Facility (FTS 778-8350; comm'l 513-527-8350).

2.3  Sample Data Input and Output from the Computer Program

2.3.1  The cell counts are input to the program.  (Counts obtained with
the Coulter Counter, must first be "corrected" for coincidence.).  The
program determines the mean count for each concentration, divides each of
the treatment means by the control mean, and subtracts the quotient from
1.0 to form an inhibition proportion for each concentration.  The
proportions are arbitrarily based on a population size of 100.
                                    154

-------
2.3.2  SMffi- Data Input And Output From The Computer program for Prooit
Analysis f£jft1gaiT Growth Test Data
PROSIT ANALYSIS-USED FOR CALCULATING THE ECU (A.1 GAL TEST)

EXCLUDING  CONTROL*  NUMBER OF CONCENTRATIONS » 3

NUMBER OF  VALUES  FOR CONTROL  » 3

PLEASE ENTER  THE   3 CORRECTED COUNTS IN CONTROL.

CONTROL COUNT »  1209*
CONTROL COUNT *  1180.
CONTROL COUNT »  1340.

   BEGIN INPUTTING  OF DATA WITH LOWEST CONCENTRATION

CONCENTRATION »  5*
PLEASE ENTER  THE   3 CORRECTED COUNTS IN CONG   5.00
COUNTS «1212.
COUNTS »1136.
COUNTS » 1204.

CONCENTRATION a  10.
PLEASE ENTER  THE   3 CORRECTED COUNTS IN CONC  10.00
COUNTS »S26.   ,                                      .
COUNTS =628.
COUNTS
CONCENTRATION  = 20.
PLEASE ENTER THE  3  CORRECTED COUNTS IN CONC  20.00
COUNTS -493.
COUNTS »416.
COUNTS »413.

CONCENTRATION  * 40.
PLEASE ENTER THE  3  CORRECTED COUNTS IN CONC  4O.OO
COUNTS i!27.     •
COUNTS »147.   .
COUNTS »147»   v  ;
                 80.
PLEASE  ip THE  3  CORRECTED COUNTS IN CONC,  30.00
COUNTS  «*?t»3
COUNTS'  *4
-------
2.3.2  Safflplt'Oata Input And  Output From The Computer Program for Probit
Analysis  of Algal Growth Test Data (Continued)
          NOTE»  CHI  SQUARED ESTIMATE QBTAINEDJY SUBTRACTION
                       PROBIT
          CONCENTRATION  PERCENT
            5.0000
           10.000O
           20.0000
           40.0000
           SO.0000
 3.41
39.13
64. SS
88.71
96.43
TABLE
  PROBABILITY

   O.OSS1
   0.3090
   0.6337
   0.8866
   0.9804
          THE CONSTANTS USEB IN THIS PROBLEM WERE?
               HETEROGENEITY FACTOR
                   NUMBER OF POINTS
                 DEGREES OF FREEDOM
                            DEVIATE
                   NUMBER OF CYCLES

           THE STATISTICS ARE»

                              AUG X
                              AVG T
                              SLOPE
                          INTERCEPT
                                  G
                        CHI SQUARED
               2.7298
               5
              • 3
               3.1820
              '• 9.
                  S.0917
                  1.2082
                 •1.9104
                  2.8363
                  1.6650
                  0.0555
                  8.189?:
                SE
                        0.2100
               POINT    '  CONCENTRATION
               EC1             2.2681
                         LOUER
                           932
                                                   1.1959
                                  UPPER
                              LIMITS

                                 3.41S1
                           r    -           SETS
            STATISTICIAN.
                                        156

-------
2.3.3   Listing Of Computer  Program For Probit  Analysis  Of Algal  Growth
Test "-"
                         BXPg(30) ,A998(20) ,A999(20) ,3X4(20) ,103(13)
                         HB»(20) ,0130(13), OBSf (20) ,2B>(20)
               CttHBSHnr X(20) ,27(20) ,3(20) ,3012(20)
                         sc(20) ,21(20) ,ss<20) ,
          c          _  _
          C    T AIB < HTSU 7UQES U1UMEL).
          C-
          C  KOTB;   THIS   7BR3IOM   VTaiTtSH   9/1S/3S
          C
          c                                             •
               ami T05,CaiSO/13.706,*.303,3.132,2.T7(S,2.571r
              * 2.*47,2.3ffl,2.30«,2.2a2,2.22a,2.201,2ol79,2.160,
              * 2.143,2.131,2.120r2.UO,2.101,3.a41,5«991,7.3ia,
              * 9.438, 11.07,12.392, 14. 087, 13.5O7,lS.9i9,lS.307,
              * 19.S7S,21.02e,22.3S2,23.S8a,24.S9«,26.29«,27.S87,
              * 28.369/
           100 rag*, •  • _    __
                   11! 'SBOBZC AtOffiZSXS^SSD ICR
               TSE 2   _    _     .
             2 JdMKTC  BXtHTUIlHB OUMUUL, NDMBHR OF CTNCNtSMlCBS » ',$!•
               MTfflT 3,H
             3 IdSai(12)
               T2BE*,1 '
               TOES
             5 K3MKCC MOHBEa.OF VamS BQR 03nBOL  - ',$)
               ACCSET S,itt
             S 5T3IWM(13)
               TSSB*,' ''
                                             _
                       srsass ansa isB',13, ' m^""*'1"' OSOHIS DT
               TSSB*,1  *
               03 10 a*i,ia     •        .
               TSE 501
           501 KEMXTC aanoL asmzr - (,S)
            10
               TSSB*, '  •
           200 nos - 1
               GO TO  260
           230 T2EB*, ' '
             •  SUM
               see -2
           260 XG2O>-1
               SOtttXi.

           521
               (33 10(300,320) ,gQS              _
           300 THE*,*   BEBOf IKtUl'illHB OF QXA HUB ICWEST
                                            157

-------
2.3.3  Listing  of Computer  Program for Proo it  Analysis of Algal Growth
Test Data  (Continued)
               00310
               TH5311
           3U KHflttC oaKsanaasar • ',$)
               tcesss 3U,z(j)
           312 KSK«(?33.13)
               XL4(J)-X(J)
               X(J)-£OS10(X(J))
                                            _
           314 JCSKHC HZRSS UEBSt CSS' /X3 , '  "mm"-!i'»in uJUWiS IN OCHC* ,F7.2)
               DO 313 I»»1,KL
               TOB 316      '
           316 PCRflSC 032ns -',$)
               JfXSSS 322,H7(S)
           313
               TZEE*,' '
               DO Z31 I-1,H
               TZHS*,' !
           231 (INITHOS
           320 1F(11O.IS.1)GO TO 230
               DO 400 I-1,N
                          ,390,390
           350 U(£ZnU>(I).I2.Q.) GO TO 330
               IF(SKMP(D.Gg.l.) <30 TO 340
               GO TO 380
           330 sax?(X)-.aooi
               GOTO 330
           340
           380
               GO TO 400
           390
           400
          C
          C
          C
          C
               SNDM.
               at«-o.
               SWE-0.
               swnx.
               DO 470 3
               IF(AB3(lD)-ia.) 401-,401,402
                                            158

-------
2.3.3   Listing of Computer Program  for  Proolt Analysis of  Algal  Srowth
Test
           .'•,:.;. QQTD 403
            403 a».H>13
            403 XT (ZC3CL} 410,420,420
            410 Bffi? (I}-Sai»<(0.000043063a*«HW.000276S«72)*MW.0001S20143)*»H).OOS
               1270073
               AI-.5-.S/ ( ( (AI*A». 0422820123) *ABK 07QS230784) *Jfflfl. } **lfi
            431
            440
                                                    )  00033441
                             -
               00 TO 442
            441
            442
               SS*f • SHK 4- WT

                             - SRHO; *
               ZT  (1OCD 470,450,450
            450 g(SHKtC) 470, 460, 460
            460
               SHHTNSMIPW5W
            470
                IT(S(«.aQ.O.) GO TO 520
                IT((SStOOCJQ.O).CR.(SSMXZ.aQ.O)} GO TO 520
                         471,472,472
            471
            472 IT OCSffi) 480,500,500
            4aOD0490>l,M
            490
                                             159

-------
2.3.3  Listing of  Computer  Program for Probit Analysis of  Algal Growth
Test Data (Continued)
               00 TO 320
           500 XF(SOXC) 520,510,510
           510
           512
         c       __
         C*     QuKCtTOB ZSQ^SCZSO
         C     TEST ABS(B(I+11-B(I)-.OCXM1)
         C     TUST* T^P^Tr ** 100
         c
           520 DO 530
           530
                         ,550,550
           540
           550 iy(IC£CL-100)5«Or530,5aO
           560 r?(SMMC5581,5iS5,565
           551 XFCBSr.ZZ. 00001)  C» TO 610
               GO TO 570
           563 TF((T25T.I2.. 00001) .CR.(ABS
-------
            *»•«,•-                                     '
2.3.3   Listing of Computer  Program for Probit  Analysis  of Algal  Growth
Test Data (Continued)                                             •
            8SO-
               00 930
                         .Z8.o.) aa TO 8«o
               IT(CBSZ(J} .08.1.) CO TO 870
               00 TO 930
           980 OBSr980)K          _
           980 reBMM?(8X,aiHISBaES OF numm** » ,13)
           990
           940 WffiB(5,10XO)IC2CL
          1003
          1010 PCraar(3X,2CH NDMEER OP G2OE3 -,I4,E.)


          1020 KBtfljCC^HJIBK S33KCESXXCS US'   }

          1030 Kagg(21X,7HKBC 7 -,J12.4)


          1040 CTBjgtaa^7H3E8B X « ,F12.4)


                    r(2JX,7H«« T - ,312.4)


                                  ,H2.4,4X,4ffiB -,F10.4)
                    3,2QSO)A
               	5,1000)G
          1X380 IC««(17X,llHINIH?CEPr -,£12.4)
          1090
                   .
             1
               ________
          1105 *uuaii(5,liOO)
          1100 ICEH»(5X,£HB30OT,fiX,13SaXC3mtaZtCH,12X,SH]X»^
                                            161

-------
2.3.3  Listing of  Computer  Program for Probit  Analysis  of Algal Growth
Test Data (Continued)

          c                                                                     .
               wosE(5,9«7}
            9*7 KSaOTC                                        95* OCNRD
             •  Tag*,' ' _
          C    G3SSOIK KM ' F ' f7ff!f
               OENJ.OI
               IFOSHn.IS.0.) GO TO 1120
           1110
               CO 7X3 (1130,1220) ,HCG
           1120
           U30
           1140
           1220 GO ID (1170,1160) ,1X05

           1170 ra035(5,iiaO) EM
           nao
           12SO «KHBV-
              1	
               TZIBV '
               TOPS*, 'IIQIE:  n* IBS EX3.  •gams IS ABOVg/BEZCW TSB
                                         ,  BflBEMS Cai/l!iLM SHXHD BE
                    , '127 KEGRED ID SOS VAIOE BEOnSS IT IHS (JUIMIIK IBS
               TSE», •IONIS AND IS COS AM SOSABOLftlZD ESTmJOED VMBE.STMHAR1
               TZHE*, 'aurrcKS  saroojvcso SB  HSEP nr SExaso TO IHE crest AND'
               T2EB*, 'ICHSH. 95> CLttflTEMCE UHHS FOR UTO HEftSQS. SHJJID EUR-'
                                     BE u»jiim.nrgrgagg qjfcjJU TCOR
                         .-1-i.-fi-ir-i  -
               TZIS5*/1
           9991 TCBSKSV/////////////////////////-)
           9399 STOP
               BESL
                               (A-H,0-Z)
               1EEMJWIHfiu:(2.S15517-«EMP»(0.3028S34lEEHP»0.010328))/
                  (l.-rtZ!ffi»(1.432788«H!P*(0.189269«H
-------
                                   TECHNICAL REPORT DATA
                            (flea* rttd iHsaucriara on rfit reverse lit fort committing)
 1. REPORT NOv
   EPA-60Q/4-35-Q14
                                                           3. RECIPIENTS ACCESSIONINO.
4. T1TUZ ANDSurriTCK

  SHORT^EMlsiCtHODS FOR ESTIMATING THE  CHRONIC
  TOXieiT£0£-EFFLUENTS ANO RECEIVING  WATERS TO
  FRESHWATER  ORGANISMS
                                                            8. REPORT DATE
                                                                            1985
                                                             . PCRPORMINQ ORGANIZATION CODE
 7. AUTHORiB)
                                                            8. PERPORMINa ORGANIZATION REPORT NO
   William B. Horning,  II and Cornelius I. Weber
 9. PSRPORMINQ ORGANIZATION NAMI AND ADDRESS
   Environmental Monitoring & Support Laooratory
   Office of Research  and Development
   U.S. Environmental  Protection Agency
   Cincinnati, Ohio 45268
                                                           10. PROGRAM CUEMfNf N6.
                                                                    AAPB1A
                                                           11. CONTRACT/QHANT NO.
 12. SPONSORING AOSNCV NAMC AND ADDRESS
   Environmental Monitoring & Support Laooratory
   Office of Research  and Development
   U.S. Environmental  Protection Agency
   Cincinnati, Ohio 45268
                                                           13. TYPf O* PWORT ANO ^tRIOO COVgH6O
                                                             	Innouse
                                                           14. SPONSOMINQ AGINCY COOC
                                                                EPA/600/06
 15* 3UP~U«M*NTAnY NQTIS
   Companion document  to EPA/4-85-013, Methods  for Measuring the Acute Toxicity
   of Effluents to Freshwater and Marine Organisms.
       This manual describes snort-term (four-  to  eight-day) methods for estimating
   the chronic toxidty  of effluents and receiving waters to a freshwater fish,  an
   invertebrate, and  an  alga.  Also Included  are guidelines on laboratory safety,
   quality assurance, facilities and equipment, dilution water, effluent sampling
   and holding, data  analysis, and organism culturing and handling-.  Listings  of
   computer programs  for Ounnett's Procedure  and Prooit Analysis are provided  in
   the Appendix.
 7.
                                KIY WORDS ANO DOCUMENT ANALYSIS
                  OMCRirroRS
                                              b.lDCNTtFISRS/OPeN ENDED TERMS
                                                                         c. COSAT) Field/Group
   Ecotoxicology
   Effluents
   Receiving Water
   Tox lefty
   Bioassay
   Industrial Waste
   Domestic Waste
                      Fish
                      Invertebrates
                      Algae
                      Freshwater Biology
                      Marine Biology
        6C
 3. DISTRIBUTION STATEMENT

  RELEASE TO PUBLIC
                                             19. SECURITY CLASS (This JteponT
                                                 UNCLASSIFIED
21. NO. OP PACES
       161
                                              2O. ScCUmTT CUAS5 (TrtU
                                                  UNCLASSIFIED
EPA Form 1220-1 73)
                                            163

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;'* "=* *S

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                                                  EPA-6QQ/4-S5-OU
                                                   September 1985
             SHORT-TERM METHODS FOR ESTIMATING
   THE CHRONIC TOXICITY OF EFFLUENTS AND RECEIVING WATERS
                  TO FRESHWATER ORGANISMS
                           Edited
                   William 8. Homing, II
                             and
                     Cornelius I. Weber
                 Biological  Methods Branch
Environmental Monitoring and Support Laboratory- Cincinnati
                   Cincinnati, Ohio  45268
ENVIRONMENTAL MONITORING AND SUPPORT LABORATORY - CINCINNATI
          -•  OFFICE OF RESEARCH AND DEVELOPMENT
            U.  5.  ENVIRONMENTAL PROTECTION AGENCY
                   CINCINNATI,  OHIO  45268

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           UNITED STATES  ENVIRONMENTAL PROTECTION AGENCY ^S|rr^ p*
                    OFFICE OF RESEARCH AND DEVELOPMENT              C      *

                                                                       Of/^

                                                                           °
                    OFFICE OF RESEARCH AND DEVELOPMENT

              ENVIRONMENTAL MONITORING AND SUPPORT LABORATORY
                              CINCINNATI. OHIO 4.5268
 fr7yo

I'  fr

   *"
DATE:    December 4, 1985

SUBJECT: Advance Copy of Chronic Toxicity Test Manual for Use in the New
         Water Quality Based Approacn to Permit Writing
                                                            J
FROM:    Cornelius I. Weber, Ph.D., Chief
         Biological Methods Branch
TO:      Water Management Division Directors
         Environmental Services Division Directors
         Permits Branch Chiefs
         Regional Water Quality Coordinators
         Senior Regional Biologists
    Attached is a prepublication copy of the manual, "Short-term Methods
for Estimating the Chronic Toxicity of Effluents and Receiving Waters to
Freshwater Organisms," prepared at the request of the Office of Water
Enforcement and Permits for use in the water quality based approach to
permitting.  Publication.of this manual was originally scheduled for
October, 1985, but was delayed because of budget restrictions during the
first two months of FY-86, when the Agency was operating under continuing
resolutions.

    Funds are now available for printing, and we anticipate that copies
of the manual will be received from the printer in February.  To obtain
additional copies at that time, please contact our Publications
Assistant, Betty Thomas, FTS 684-7301.-
Attachment (1):
As Stated

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                                   NOTICE

    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.
                                     n

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                                  FOREWORD

    Environmental measurements are required to determine the quality of
ambient water, the character of effluents, and the effects of pollutants
on aquatic life.  The Environmental Monitoring and Support Laboratory -
Cincinnati (EMSL-Cincinnati) operates an Agency-wide quality assurance
program to assure standardization and quality control of systems for
monitoring water and wastewater, and conducts research to develop,
evaluate, and promulgate methods to:

        Measure the presence and concentration of physical, chemical, and
        radiological pollutants in water, wastewater, bottom sediments,
        and solid waste.

    •   Concentrate, recover, and identify enteric viruses, bacteria, and
        other microorganisms in water, wastewater, and municipal sludge.

        Measure the effects of pollution on freshwater, estuarine, and
        marine organisms, including the phytoplankton, zooplankton,	
        periphyton, macrophyton, macroinvertebrates, and fish.

        Automate the measurement of the physical, chemical, and
        biological quality of water.                        _..,.,«


    The Federal Water Pollution Control Act Amendments of 1972
(PL 92-500) and the Clean Water Act (CWA) of 1977 (PL 95-217) explicitly
state that it is the national policy that the discharge of toxic
substances in toxic amounts be prohibited.  Determination of the toxicity
of effluents, therefore, plays an important role in identifying and
controlling toxic discharges to surface waters.  This report provides
standardized methods for estimating the chronic toxicity of effluents and
receiving waters to aquatic life for use by the U.S. Environmental
Protection Agency (USEPA) regional and state,programs, and National
Pollutant Discharge Elimination System (NPOES) permittees.
                                    Robert L. Booth
                                    Director
                                    Environmental Monitoring and
                                    Support Laboratory - Cincinnati

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                                   PREFACE

    This manual 1s the first Agency methods manual for estimating the
chronic toxicity of effluents and receiving waters.  The draft was
reviewed by the Bioassay Subcommittee of the EMSL-Cincinnati Biological
Advisory Committee, USEPA headquarters and regional staff, other Federal
agencies, state and interstate water pollution control programs,
environmental protection groups, trade associations, major industries,
consulting firms, academic institutions engaged in aquatic toxicology
research, and other interested parties in the private sector.

             -   EMSL-CINCINNATI  BIOASSAY  SUBCOMMITTEE  MEMBERS

    William Peltier, Subcommittee Chairman
    Environmental Services Division, Region 4
    Peter Nolan, Environmental Services Division, Region 1
    Thomas Fikslin, Environmental Services Division, Region 2
    Ronald Preston, Environmental Services Division, Region 3
    Lee Tebo, Environmental Services Division, Region 4
    Charles Steiner, Environmental Services Division, Region 5
    David Parrish, Environmental Services Division, Region 6
    Bruce Littell, Environmental Services Division, Region 7  .
    Leo Mosby, Environmental Services Division, Region 7
    Loys Parrish, Environmental Services Division, Region 8
    James Lazorchak, Water Management Division, Region 8
    Milton Tunzi, Environmental Services Division, Region 9
    Joseph Cummins, Environmental Services Division, Region  10
    Robert Schneider, National Enforcement Investigations Center, Denver
    Wesley Kinney, Environmental Monitoring Systems Laboratory - Las Vegas
    Steven Schimmel, Environmental Research Laboratory - Narragansett
    Douglas Middaugh, Environmental Research Laboratory - Gulf Breeze
    Donald Mount, Environmental Research Laboratory - Duluth
    Alan Nebeker, Environmental Research Laboratory - Corvallis
    Rick Brandes, National Pollutant Discharge Elimination System
    Technical Support Branch, Permits Division, Office of Water
    Enforcement and Permits
    Edward Bender, Compliance Branch, Enforcement Division, Office of
    Water Enforcement and Permits
    Thomas Murray, Monitoring Branch, Monitoring and Data Support
    Division,"Office of Water Regulations and Standards
    Stephen Ells, Environmental Effects Branch, Health and Environmental
    Review Division, Office .of Toxic Substances
                              Cornelius I. Weber, Ph.D.
                              Chairman, Biological Advisory Committee
                              Chief, Biological Methods Branch
                              Environmental Monitoring and Support
                              Laboratory - Cincinnati
                                     iv

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                                  ABSTRACT

    This manual describes short-term (four- to eight-day) methods for
estimating the chronic toxicity of effluents and receiving waters to a
freshwater fish, an invertebrate, and an alga.  Also included are
guidelines on'laboratory safety, quality assurance, facilities and
equipment, dilution water, effluent sampling and holding, data analysis,
report preparation, and organism culturing and handling.  Listings of
computer programs for Ounnett's Procedure and Probit Analysis are
provided in the Appendix.

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                                  CONTENTS

Foreword .	*	   iii
Preface	    iv
Abstract	     v
Figures	   vii
Tables	   vii
Acknowledgments  	  viii

      1. Introduction	     1
      2. Short-Term Methods for Estimating Chronic Toxicity  ...     3
      3. Health and Safety   	     6
      4. Quality Assurance   	 .....     8
      5. Facilities and Equipment	'	    13
      6. Test Organisms  .	    15
      7. Dilution Water	    17
      8. Effluent and Receiving Water Sampling and Sample Handling    19
      9. Chronic Toxicity Test End Pofnts and Data Analysis  ...    22
     10. Report Preparation  	    26
     11. Fathead Minnow (Pimephales promelas) Larval Survival
         and Growth'Test	    28
     12. Fathead Minnow (Pimephales promelas) Embryo-larval
         Survival and Teratogemcity Test	    42
     13. Ceriodaphnia Survival.and Reproduction Test 	    58
     14. Algal (Selenastrum capricornutum) Growth Test 	    76

Selected References	    96
Appendix   . ^	   105
      A. Validating Normality and Homogeneity of Variance
         Assumptions   . . .	   106
      8. Arc Sine Square-Root Transformation   	   Ill
      C. Dunnett's Procedure   	   113
      0. Steel's Many-one Rank Test	   132
      E. Fisher's Exact Test	   135
      F. Probit Analysis	   144
                                     VI

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                                  FIGURES

Number                                      "                      Page
   1. Control chart	     12
                                  TABLES

Number                                .                             page -

 1. Preparation of synthetic fresh water.   . . .	     18

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                               ACKNOWLEDGMENTS

    Materials  in  this  manual  were taken  in  part from the following
 sources:  USEPA, 1975,  Methods for Acute  Toxieity Tests  with  Fish,
 Macroinvertebrates,  and  Amphibians,   Environmental  Research  Laboratory,
 U.  S.  Environmental  Protection Agency, Duluth,  Minnesota,
 EPA-660/3-75-009;  USEPA, 1979, Handbook  for Analytical  Quality Control  in
 Water  and Wastewater Laboratories, Environmental  Monitoring  and Support
 Laboratory - Cincinnati, U. S. Environmental  Protection Agency,
 Cincinnati, Ohio,  EPA-600/4-79/019;  USEPA,  1979,  Interim NPOES Compliance
 Biomonitoring  Inspection Manual,  Enforcement  Division,  Office  of Water
 Enforcement, U. S. Environmental  Protection Agency,  Washington, D.C.;
 Peltier,  W. H., and  C. I. Weber,  1985, Methods  for  Measuring the Acute
 Toxicity  of Effluents  to Freshwater  and  Marine  Organisms, Environmental
 Monitoring and Support Laboratory -  Cincinnati, U.  S. Environmental
 Protection Agency, Cincinnati, Ohio,  EPA-600/4-85/013;  Mount,  D. I., and
 T.  J.  Norberg, 1984, A Seven-day  Life-cycle Cladoceran  Test,   Environ.
 Toxicol.  Chem. 3:425-434; Norberg, T., and  0. I.  Mount,  1985,  A New
 Subchronic Fathead Minnow (Pimephales promelas) Toxicity Test,  Environ.
 Toxicol.  Chem. (In press); and Miller, W. £., J.  C.  Greene, and
 T.  Shiroyama, 1978r  The  Selenastrum  capricornutum Printz Algal  Assay
 Bottle Test, Environmental Research  Laboratory, U.  S. Environmental
 Protection Agency, Corvallis,  Oregon, EPA-600/9-78-018.

    The assistance of the following  members of  the  staff of the Aquatic
 Biology Section, Biological Methods  Branch, EMSL-Cincinnati, is
 gratefully acknowledged: Quentin  Pickering  prepared  the  section on the
 fathead minnow larval survival and growth test; Timothy  Neiheisel
 prepared  the section on  the fathead minnow  embryo-larval survival and
 teratogenicity test; Philip Lewis  prepared  the  section on the
 Ceriodaphnia survival and reproduction test; Ernest Robinson provided the
 precision  data for Selenastrum capricornutum; James Dryer provided the
 listings  of the computer programs, and assisted in preparing other
 materials  on test data analysis;  and Cordelia Newell, Diane Schirmann,
 Dianne White, and Janice Miller provided valuable secretarial  assistance.

    Many helpful  suggestions for  the revision of the manual  were provided
 by members of the Bioassay Subcommittee  in the first and second round
 review.  William Peltier, Chairman, Bioassay Subcommittee, deserves
 special recognition for the valuable assistance provided in  the
 preparation of the final  draft of the manual.

    John Menkedick and Florence Kessler,  Statisticians,  Computer Sciences
Corporation, on-site contractor at the Andrew W. Breidenbach
Environmental Research Center, U. S.  Environmental Protection Agency,
Cincinnati, provided materials for inclusion in Section  9, and assisted
 in the preparation of materials on data analysis and precision for  other
sections and the Appendix.
                                   viii

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    The editors also wish to acknowledge the review comments received
from the following persons: Howard Alexander, Dow Chemical U.S.A.,
Midland, Michigan; R. Clifton Bailey, U. S. Environmental Protection
Agency, Washington, DC; James Baker, U. S. Environmental Protection
Agency, Denver, Colorado; Dorothy Berner, Temple University,
Philadelphia, Pennsylvania; F. A. Blanchard, Dow Chemical U.S.A, Midland,
Michigan; K. M. Bodner, Dow Chemical U.S.A, Midland, Michigan; Douglas
Burnhara, Vermont Agency of Environmental Conservation, Montpelier,
Vermont; Oscar Cabra, U. S. Environmental Protection Agency, Dallas,
Texas; Joseph Carra, U. S. Environmental Protection Agency, Washington,
DC;'  Larry Claxton, U. S. Environmental Protection Agency, Research
Triangle Park, North Carolina; Gary Collins, U. S. Environmental
Protection Agency, Cincinnati, Ohio; Jody Connor, New Hampshire Water
Pollution Control Commission, Concord, New Hampshire; Nelson Cooley,
U. S. Environmental Protection Agency, Gulf Breeze, Florida; John Cooney,
Battelle Columbus Laboratories, Columbus, Ohio; Frank Covington, U. S.
Environmental Protection Agency, San Francisco, California; U. M.
Cowgill, Dow Chemical U.S.A., Midland, Michigan; Michael OeGraeve,
Battelle Columbus Laboratories, Columbus, Ohio; D. C. Dill, Dow Chemical
U.S.A., Midland, Michigan; Kenneth Dostal, Water Engineering Research
Laboratory, U. S. Environmental Protection Agency, Cincinnati, Ohio;
Thomas Duke, U. S. Environmental Protection Agency, Gulf Breeze, Florida;
Robert Elliott, U. S. Environmental Protection Agency, Seattle,
Washington; Robert Estabrook, New Hampshire Water Pollution Control
Conraission, Concord, New Hampshire; James Fava, EA Engineering, Science,
and Technology, inc., Sparks, Maryland; David Flemer, U. S. Environmental
Protection Agency,, Washington, DC; Peter Gartside, University of
Cincinnati Medical School, Cincinnati, Ohio; F. M. Gersich, Dow Chemical
U.S.A., Midland, Michigan; James Gillett, Cornell University, Ithaca, New
York; Miriam Goldberg, U. S. Environmental Protection Agency, Washington,
DC; Larry Goodman, U. S. Environmental Protection Agency, Gulf Breeze,
Florida; Joseph Gorsuch, Eastman Kodak Company, Rochester, New York;
David Gruber, Biological Monitoring, Inc., Blacksburg, Virginia; Scott
Hall, Johns Hopkins University, Baltimore, Maryland; Jerry Hamelink,
Lilly Research Laboratory, Greenfield, Indiana; David Hansen, U. S.
Environmental Protection Agency, Narr.agansett, Rhode Island; David
Hutton, Haskell Laboratory for Toxicology, I.E. DuPont de Nemours and
Company, Newark, Delaware; Kathleen Keating, Rutgers State University,
Park Ridge, New Jersey; Stephen Klaine, Memphis State University,
Memphis, Tennessee; Armond Lemke, U. S. Environmental Protection Agency,
Dulutn, Minnesota; Michael Lewis, Proctor and Gamble Company, Cincinnati,
Ohio; Elizabeth Loevey, U. S. Environmental Protection Agency,
Washington, DC; Donald Lollock, California Department of Fish and Game,
Sacramento, California; Leif Marking, U. S. Fish and Wildlife Service, La
Crosse, Wisconsin; Michael Martin, California Department of Fish and
Game, Monteray, California; Jack Mattice, Electric Power Research
Institute, Palo Alto, California; Foster Mayer, U. S. Environmental
Protection Agency, Gulf Breeze, Florida; M. A. Mayes, Dow Chemical
U.S.A., Midland, Michigan; Robert Medz, U. S. Environmental Protection
Agency, Washington, DC; Gary Neuderfer, New York Department of

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Environmental Control, Avon, New York; Paul Pan, U. S. Environmental
Protection Agency, Washington, DC; Rod Parri|h, U. S. Environmental
Protection Agency, Gulf Breeze, Florida; Gilbert Potter, U. S.
Environmental Protection Agency, Las Vegas, Nevada; Ronald Raschke, U. S.
Environmental Protection Agency, Athens, Georgia; John Rogers, University
of Wisconsin, Superior, Wisconsin; Landon Ross, Florida Department of
Environmental Regulation, Tallahassee, Florida; Richard Scnoettger, U. S.
Fish and Wildlife Service, Columbia, Missouri; William Selconis,
Hoffman-LaRoche, Belvidere, New Jersey; Judith Shaw, American Petroleum
Institute, Washington, DC; Russell Sherer, South Carolina Department of
Health and Environmental Control, Columbia, South Carolina; Richard
Steele, U. S. Environmental Protection Agency, Narragansett, Rhode
Island; Charles Stephan, U. S. Environmental Protection Agency, Duluth,
Minnesota; James Stiebing, U. S. Environmental Protection Agency,
Seattle, Washington; Daniel Sullivan, U. S. Environmental Protection
Agency, Edison, New Jersey; Jerry Stara, U. S. Environmental Protection
Agency, Cincinnati Ohio; I. T. Takahashi, Dow Chemical U.S.A, Midland,
Michigan; James Swigert, Indiana State Board of Health, Indianapolis,
Indiana; Frieda Taub, University of Washington, Seattle, Washington;
William Telliard, U. S. Environmental Protection Agency, Washington, DC;
Roy Thompson, Imperial Chemical Industries, Devon, England; Glen Thursby,
U. S. Environmental Protection Agency, Narragansett,.Rhode Island;
William Tucker, Illinois Environmental Protection Agency, Springfield,
Illinois; William Waller, University of Texas at Dallas, Richardson,
Texas; Gerald Walsh, U. S. Environmental Protection Agency, Gulf Breeze,
Florida; Barbara Walton, Oak Ridge National Laboratory, Oak Ridge,
Tennessee; Thomas Wallingham, U. S. Environmental Protection Agency,
Denver, Colorado;  James Whitaker, Illinois Environmental Protection
Agency, Springfield, Illinois; J. I. Whitfield, Dow Chemical U.S.A.,
Midland, Michigan; John Winter, U. S. Environmental Protection Agency,
Cincinnati, Ohio; and William Wuerthele, U. S. Environmental Protection
Agency, Denver, Colorado.

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                                  SECTION 1

                                 INTRODUCTION

1.1  The Federal Water Pollution Control Act Amendments of 1972 (PL 92-500)
and the Clean Water Act (CWA) of 1977 (PL 95-217) were enacted to restore
and maintain the chemical, physical, and biological integrity of the
Nation's waters (Section 101[a]), and contained specific or implied
requirements for the collection of b i onion i tor ing data in at least 15
sections.

1.2  The Declaration of Goals and Policy, Section 101(a)(3), in these two
laws, states that "it is the national goal that the discharge of toxic
pollutants in toxic amounts be prohibited."  To achieve the goals of this
legislation, extensive effluent toxicity screening programs were conducted
during the 1970s by the regions and states.  Acute toxicity tests (USEPA,
1975; Peltier, 1978) were used to measure effluent toxicity and to estimate
the safe concentration of toxic effluents in receiving waters.  However,
for those effluents that were not sufficiently toxic to cause mortality in
acute (one- to four-day) fests, short-term inexpensive methods were not
available to detect the more subtle, low-level, long-term, adverse effects
of effluents on aquatic organisms, such as reduction in growth and
reproduction, and occurrence of terata.  Fortunately, rapid developments in
toxicity test methodology during the past five years have resulted in the
availability of several methods that permit  detection of the low-level,
adverse effects (chronic toxicity) of effluents in eight days or less.
                  *>
1.3  As a result of the increased awareness  of the value of'effluent
toxicity test data for toxics control in the National Pollutant Discharge
Elimination System (NPOES) permit program, which emerged from the extensive
effluent toxicity monitoring activities of the regions and states, and the
recent availability of short-term chronic toxicity test methods, the U. S.
Environmental Protection Agency (USEPA) issued a national policy statement
entitled, "Policy for the Development of Water Quality-Based Permit
Limitations for Toxic Pollutants," in the Federal Register Vol. 49, No. 48,
Friday, March 9, 1984.  A technical support  document on the use of effluent
and receiving water toxicity data also has been prepared by the Office of
Water Enforcement and Permits (OWE?) to provide additional guidance on the
implementation of the biomonitoring policy (USEPA, 1985).

1.4  This new Agency policy proposes the use of toxicity data to assess and
control the discharge of toxic substances to the Nation's waters through
the NPDES permits program.  The policy states that "biological testing of
effluents is an important aspect of the water quality-based approach for
controlling toxic pollutants.  Effluent toxicity data, in conjunction with
other data, cain be used to establish control priorities, assess compliance
with State water quality standards, and set  permit limitations to achieve
those standards."  All states have water quality standards which include
narrative statements prohibiting the discharge of toxic materials in toxic
amounts.

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1.5  The four short-term tests described in this manual are for use in the
NPOES Program to estimate one or more of the following: (1) the chronic
toxicity of effluents collected at the end of the discharge pipe and tested
with a standard dilution water (moderately hard synthetic freshwater in Table
1, p. 18); (2) the chronic toxicity of effluents collected at the end of the
discharge pipe and tested with dilution water consisting of non-toxic
receiving water collected upstream from the outfall, or with other
uncontaminated surface water or standard dilution water having approximately
the same hardness as the receiving water; (3) the toxicity of receiving water
downstream from the outfall; and (4) the effects of multiple discharges on
the quality of the receiving water.  The tests may also be useful in
developing site-specific water quality criteria.

1.6  These methods were developed to provide the most favorable cost-benefit
relationship possible, and are intended for use in effluent toxicity tests
performed on-site, where time is very costly, and for toxicity tests with
effluent samples shipped to central and distant laboratories, where the
volume of waste shipped.must be kept to a minimum.

    The tests include:

    1. Seven-day, sub-chronic, fathead minnow (Pimephales promelas),
       static renewal, larval survival and growth test.

    2. Seven-day, (three-brood), chrom'c, Ceriodaphnia dubia, static
       renewal, survival and reproduction test.

    3. Eight-day, sub-chronic, fathead minnow (Pimephales promelas),
       static renewal, embryo-larval survival and teratogenicity test.

    4. Four-day, chronic, Selenastrum capricornutum, static, growth test.

1.7  The first two tests were adapted from methods developed by
Or. Donald Mount and Teresa Norberg, Environmental Research Laboratory,
USEPA, Duluth, Minnesota (Mount and Norberg, 1984; Norberg and Mount,
1985).  The third test was adapted from a method developed by Drs. Wesley
Birge and Jeffrey Black, Graduate Center for Toxicology, University of
Kentucky, Lexington, Kentucky (Birge and Black, 1981).  The fourth test,
a 96-h, multi-generation test utilizing the freshwater alga, Selenastrum
capricornutum, was adapted from the publications of the Environmental
Research Laboratory - Corvallis (USEPA, 1971; Miller et al., 1978).

1.8  The Environmental Monitoring and Support Laboratory - Cincinnati
(EMSL-Cincinnati) has incorporated the short-term chronic and sub-chronic
tests Into this manual for use by regulatory agencies involved in
biological monitoring of wastewater under the NPOES program.  Authority
for promulgating test procedures for the analysis of pollutants is
contained in Section 304(h) of the CWA.

1.9  The manual was prepared in the established EMSL-Cincinnati format
(Kopp, 1983) so that each method can be used independently of the other
methods.

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          ... .... ..                SECTION 2

              SHORT-TERM METHODS FOR ESTIMATING CHRONIC TOXICITY

2.1  The objective of aquatic toxicity tests with effluents or pure
compounds is to estimate the "safe" or "no effect" concentration of these
substances, which is defined as the concentration which will permit normal
propagation of fish and other aquatic life in the receiving waters.  The
endpoints that have been considered in tests to determine the adverse
effects of toxicants include death and survival, decreased reproduction and
growth, locomotor activity, gill ventilation rate, heart rate, blood
chemistry, histopathology, enzyme activity, olfactory function, and
terata.  Since it is not feasible to detect and/or measure all of these
(and other possible) effects of toxic substances on a routine basis,
observations in toxicity tests generally have been limited to .only a few
effects, such as mortality, growth, and reproduction.

2.2  Acute mortality is.an obvious and easily observed effect, which
accounts for its wide use in the early period of evaluation of the toxicity
of pure compounds and complex effluents.  The results of these tests were
usually expressed as the concentration lethal to 50% of the test organisms
(LC50) over relatively short exposure periods (two to four days).

2.3  As exposure periods of acute tests were lengthened, the LC50 and
lethal threshold concentration were observed to decline for many
compounds.  By lengthening the tests to include one or more complete life
cycles and observing the more subtle effects of the toxicants, such as a
reduction in growth and reproduction, more accurate, direct, estimates of
the threshold or safe concentration of the toxicant could be obtained.
However, laboratory life-cycle tests may not accurately estimate the safe
concentration of toxicants because they are conducted with a limited number
of species under highly controlled, steady-state conditions, and the
results do not include the effects of the stresses to which the organisms
would ordinarily be exposed in the natural environment.

2.4  An early published account of a full life-cycle, fish toxicity test
was that of Mount and Stephan (1967).  In this study, fathead minnows
(Pimephales promelas) were exposed to a graded series of pesticide
concentrations throughout their life cycle, and the effects of the toxicant
on survival, growth, and reproduction were measured and evaluated.  This
work was soon followed by full life-cycle tests using other toxicants and
fish species.

2.5  McKira (1977) evaluated the data from 56 full life-cycle tests, 32 of
which used the fathead minnow, and concluded that the embryo-larval and
early juvenile life-stages were the most sensitive stages.  He proposed the
use of partial life-cyle toxicity tests with the early life-stages (ELS) of
fish to establish water quality criteria.

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2.6  Macek and Sleight (1977) found that exposure of critical life-stages
of fish to toxicants provides estimates of chronically safe concentrations
remarkably similar to those derived from full life-cycle toxicity tests,
and reported that "for a great majority of toxicants, the concentration
which will not be acutely toxic to the most sensitive life stages is the
chronically safe concentration for fish, and that the most sensitive life
stages are-the embryos and fry."  Critical life-stage exposure was
considered to be exposure of the embryos during most, preferably all, of
the embryogenic (incubation) period, and exposure of the fry for 30 days
post-hatch for warm water fish with embryogenic periods ranging from one to
14 days, and for 60 days post-hatch for fish with longer embryogenic
periods.  They concluded that in the majority of cases, the maximum
acceptable toxicant concentration (MATC) could be estimated from the
results of exposure of the embryos during incubation, and the larvae for 30
days post-hatch.

2.7  Because of the high cost of full life-cycle fish toxicity tests and
the emerging concensus that the ELS test data would be adequate for
estimating chronically safe concentrations, there was a rapid shift by
aquatic toxicologists to 30- to 90-day ELS toxicity tests for estimating
chronically safe concentrations in the late 1970s.  In 1980, USEPA adopted
the policy that ELS test data could be used in establishing water quality
criteria if data from full life-cycle tests were not available (USEPA,
1980a).

2.8  Published reports of the results of ELS tests indicate that the
relative sensitivity of growth and survival as endpoints may be species
dependent, toxicant dependent, or both.  Ward and Parrish (1980) examined
the literature on ELS tests that used embryos and juveniles of the salt
water species, sheepshead minnow (Cyprinodon variegatus), and found that
growth was not a statistically sensitive indicator of toxicity in 16 of 18
tests.  They suggested that the ELS tests be shortened to 14 days posthatch
and that growth be eliminated as an indicator of toxic effects.

2.9  In a review of the literature on 173 fish full life-cycle and ELS
tests performed to determine the chronically safe concentrations of a wide
variety of toxicants, such as metals, pesticides, organics, inorganics,
detergents, and complex effluents, Woltering (1984) found that at the
lowest effect'concentration, significant reductions were observed in fry
survival in 57%, fry growth in 36%, and egg hatchability in.19% of the
tests.  He also found that fry survival and growth were very often equally
sensitive, and concluded that the growth response could be deleted from
routine application of the ELS tests.  The net result would be a
significant reduction in the duration and cost of screening tests with no
appreciable impact on estimating MATCs for chemical hazard assessments.
Benoit, et al., (1982), however, in early life-stage tests with four
organic chemicals, found larval growth to be the most significant measure
of effect, and survival to be equally or less sensitive than growth.

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2.10  Efforts to further reduce the length of partial life-cycle toxicity
tests for fish without compromising their predictive value have resulted in
the devtlopratnt of an eight-day, embryo-larval survival and teratogenicity
test for fish and and other aquatic vertebrates  (Birge and Black,  1981;
Birge et al., 1985), and a seven-day larval survival and growth test (Mount
et al., 1984; Norberg and Mount, 1985).

2.11  The similarity of estimates of chronically safe concentrations of
toxicants derived from short-term, embryo-larval survival and
teratogenicity test to those derived from full life-cycle tests has been
demonstrated by Birge et al. (1981), Birge and Cassidy (1983), and Birge
et al. (1985).

2.12  Use of a seven-day, fathead minnow larval survival and growth test
was first proposed by Norberg and Mount at the 1983 annual meeting of the
Society for Environmental Toxicology and Chemistry (Norberg and Mount,
1983).  This test was subquently used by Mount and associates in field.
demonstrations at Lima,.Ohio (Mount, et al., 1984), and-at many other
locations.  Growth was frequently found to be more sensitive than survival
in determining the effect of complex effluents.

2.13  Norberg and Mount (1985) performed three single toxicant fathead
minnow larval growth tests with zinc, copper, and DURSBANR, using
dilution water from Lake Superior.  The results were comparable to, and had
confidence intervals that overlapped with, chronic values reported in the
literature for both ELS and full life-cycle tests.

2.14 "Efforts to develop a short-term cladoceran chronic toxicity test as a
substitute for the 21- to 28-day Daphnia chronic toxicity test have
resulted in a seven-day (three-brood) survival and reproduction test using
Ceriodaphm'a (Mount and Norberg, 1984).  This test has been shown to
provide data comparable to the previous, longer-term Daphnia chronic tests,
and has also been used extensively by Mount and associates in field
demonstrations.

2.15  The algal toxicity test described in this manual is a shortened
version of the Agency's algal growth potential test (Miller et al., 1978).
The 96-h length of the toxicity test period spans several generation times
and, therefore, more than meets the requirements for a full life-cycle
chronic test. "

2.16  The use, of short-term,-subchronic and chronic toxicity tests in the
NPDES Prograa is especially attractive because they provide a more direct
estimate of the safe concentration of effluents in receiving waters than
was provided by acute toxicity tests, at an only slightly increased level
of effort, compared to that required by the fish full life-cyle chronic and
(30-day) ELS tests and the 21- to 28-day cladoceran tests.

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                                   SECTION 3
                               :.   <:.-        :,,«••  -•¥
                              HEALTH AND SAFETY1
3.1  GENERAL PRECAUTIONS
3.1.1  Collection  and  use of effluents  in toxicity tests  may involve
significant risks  to personal  safety and  health.   Personnel  collecting
effluent samples and conducting  toxicity  tests  should  take all  safety
precautions necessary  for the prevention  of bodily injury and illness which
might result from  ingestion  or invasion of infectious  agents, inhalation  or
absorption of corrosive or toxic substances through skin  contact,  and
asphyxiation due to lack  of  oxygen or presence  of  noxious gases.
3.1.2  Prior to sample collection and laboratory work,  personnel should
determine that all necessary safety equipment and  materials  have been
obtained and are in good  condition.
3.2  SAFETY EQUIPMENT
3.2.1  Personal Safety Gear
    Personnel should use  safety  equipment,  as required, such  as rubber
aprons, laboratory coats,  respirators-,  gloves,,  safety glasses, hard  hats,
and safety shoes.
3.2'.2  Laboratory Safety  Equipment
    Each laboratory (including mobile laboratories)  should be provided with
safety equipment such  as  first-aid kits,  fire extinguishers,  fire  blankets,
emergency showers, and eye fountains.
3.3  GENERAL LABORATORY AND  FIELD  OPERATIONS
3.3.1.  Work with effluents  should  be performed in compliance with accepted
rules pertaining to the handling  of hazardous materials (see  safety
manuals, Paragraph 3.5).   It is  recommended that personnel collecting
samples and performing toxicity  tests should  not work alone.
3.3.2.  Because the chemical composition of effluents is usually only
poorly known, they should  be considered as potential health hazards, and
exposure to them should be minimized.
3.3.3.  It is advisable to cleanse exposed parts of the body  immediately
after collecting effluent  samples.
3.3.4.  All  containers should be adequately labeled to indicate their
contents.
Adapted from: Peltier and Weber (1985).

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3.3.5.  Good housekeeping contributes to safety and reliable results.
3.3.6.  Electrical equipment or extension cords not bearing the approval of
Underwriter Laboratories must not be used.  Ground-fault interrupters must
be installed in all "wet" laboratories where electrical equipment is used.
3.3.7.  Mobile laboratories should be properly grounded to protect against
electrical shock."
3.4  DISEASE PREVENTION
3.4.1  Personnel handling samples which are known or suspected to contain
human wastes should be immunized against tetanus, typhoid fever, and polio.
3.5  SAFETY MANUALS
3.5.1  For further guidance on safe practices when collecting effluent
samples and conducting toxicity tests, check with the permittee and consult
general industrial safety manuals, including USEPA (1977), and Walters and
Jameson (1984).

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                                  SECTION 4

                              QUALITY  ASSURANCE1

4.1  INTRODUCTION

4.1.1  Quality Assurance (QA) practices for effluent toxicity tests consist
of all aspects of the test that affect data quality, such as: (1) effluent
sampling and handling; (2) the source and condition of the test organisms;
(3) condition of equipment; (4) test conditions; (5) instrument
calibration; (6) replication; (7) use of reference toxicants; (8) record
keeping; and (9) data evaluation.  For general guidance on good laboratory
practices related to toxicity'testing, see:  FDA, 1978; USEPA, 1979d,
1980b, and 1980c; and DeWoskin, 1984.

4.2  EFFLUENT AND RECEIVING WATER SAMPLING AND HANDLING

4.2.1  Effluent samples.collected for on-site and off-site testing must be
preserved as described in Section 8, Effluent and Receiving Water Sampling
and Sample Handling.

4.3  TEST ORGANISMS

4.3.1  The test organisms used in the procedures described in this manual
are the fathead minnow, Pimephales promelas, the cladoceran, Ceriodaphnia
dubla, and the green alga, SelenaTtrum capricornutunu  The organjsms used
should be disease-free, and snould be positively identified to species.

4.4  FACILITIES, EQUIPMENT, AND TEST CHAMBERS

4.4.1  Laboratory and bioassay temperature control equipment must be
adequate to maintain recommended test water temperatures.  Recommended
materials must be used in the fabrication of the test equipment which comes
in contact with the effluent  (see Section 5, Facilities and Equipment).

4.5  ANALYTICAL METHODS

4.5.1  Routine chemical and physical  analyses must include established
quality assurance practices outlined  in Agency methods manuals (USEPA,
1979a,b).

4.6  CALIBRATION AND STANDARDIZATION

4.6.1  Instruments used for routine measurements of chemical and physical
parameters such as pH, DO, temperature, conductivity, alkalinity, and
hardness, must be calibrated  and standardized according to instrument
manufacturers procedures as indicated in the general section on quality
assurance (see EPA Methods 150.1, 360.1, 170.1, and 120.1, USEPA, 1979b).
Adapted from: Peltier  (1978), Peltier and Weber (1985),
 and USEPA (1979a).

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4.6.2  Wet chemical methods used to measure hardness and alkalinity must be
standardized according to the procedures for those specific EPA methods (see
EPA Methods 130.2 and 310.1, USEPA 1979b). '

4.7  DILUTION WATER

4.7.1  The-dilution water used in the toxicity tests may be synthetic water,
receiving water, or ground water, appropriate to the objectives of the study
and logistical constraints, as discussed in Section 7.

4.8  TEST CONDITIONS

4.3.1  Water temperature must be maintained within the limits specified for
each test.  Dissolved oxygen (DO) concentrations and pH should be checked at
the beginning of the test and daily throughout the test period.

4.9  TEST ACCEPTABILITY

4.9.1  The results of the fathead minnow or Ceriodaphnia 24-h reference
toxicant tests are unacceptable if the survival in the controls is less than
90%.  For effluent toxicity tests to be acceptable, control survival must be
at least 80%.  The results of the algal toxicity test are unacceptable if
the cell density in the controls after 96 h is less than 106 cells/mL.

4.9.2  An individual test may be conditionally acceptable if temperature,
DO, and other specified conditions fall outside specifications, depending on
the degree of the departure and the objectives of the tests (see test
condition summaries).  The acceptability of the test would depend on the
best professional judgment and experience of the investigator.  The
deviation from test specifications must be noted when reporting data from
the test.

4.10  PRECISION

4.10.1 The ability of the laboratory personnel to obtain consistent, precise
results must be demonstrated with reference toxicants before they attempt to
measure effluent toxicity.  The single laboratory precision of each type of
test to be used in a laboratory should be determined by performing five or
more tests with a reference toxicant.  In cases where the test data are used
in the Probit Analysis (see Section 9), precision can be described by the
mean, standard deviation, and relative standard deviation (percent
coefficient of variation, or CV) of the calculated end points from the
replicated tests.  However, in cases where the results are reported in terms
of the No-Observed-Effect Concentration (NOEC) and Lowest-Qbserved-Effect
Concentration (LOEC) (see Section 9), precision can only be described by
listing the NOEC-LOEC interval for each test.  In this case, it is not
possible to express precision in terms of a commonly used statistic.  For
instance, when all tests of the same toxicant yield the same NOEC-LOEC
interval, maximum precision has been attained.  However, the "true" no
effect concentration could fall anywhere within the interval, NOEC +
(NOEC-LOEC).

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4.10.2  It should be noted here that the dilution factor selected for a
test deteraines the width of the NOEC-LOEC Interval and the Inherent
maxima® precision of the test.  As the absolute value of the dilution
factor decreases, the width of the NOEC-LOEC interval increases, and the
Inherent maximum precision of the test decreases.  When a dilution factor
of 0.3 is used, the NOEC could be considered to have a relative variability
as high as- + 300%.  With a dilution factor of 0.5, the NOEC could be
considered to have a relative variability of + 100%.  Other factors which
can affect test precision include test organism age, condition, and
sensitivity, temperature control, and feeding.

4.11 REPLICATION AND TEST SENSITIVITY

4.11.1  The sensitivity of the tests will depend in part on the number of
replicates, the probability level selected, and the type of statistical
analysis.  The minimum recommended number of replicates varies with the
test and the statistical method used, .and is discussed in Section 9 and in
each method.  The sensitivity of the test will increase as the number of
replicates 1s increased.

4.12  QUALITY OF TEST ORGANISMS

4.12.1  If the laboratory does not have an ongoing test organism culturing
program and obtains the test organisms from an outside source, the
sensitivity of each batch of test organisms must be evaluated with a
reference toxicant in a toxicity test performed concurrently with the
effluent and/or receiving water toxicity tests.  If the laboratory
maintains breeding cultures, the sensitivity of the offspring should be
determined in a toxicity test performed with a reference toxicant at least
once each month.  If preferred, this reference toxicant test may be
performed concurrently with an effluent toxicity test.  A 24-h acute
toxicity test is used to determine the sensitivity of fathead minnows and
Ceriodaphnia.  For the acute toxicity test design, see Peltier and Weber
(1985).  A 96-h toxicity test is used to determine the sensitivity of
Selenastrum.

4.12.2  The sensitivity of fathead minnow larvae is determined with newly
hatched larvae as used in the growth and survival or embryo-larval test.
The sensitivity of Ceriodaphnia is determined using animals less than 24 h
old, and which were released within the same 4-h period.

4.12.3  Three reference toxicants are available from EMSL-Cincinnati to
establish the precision and validity of toxicity data generated by
biomonitoring laboratories: sodium dodecylsulfate (SDS), sodium
pentachlorophenate (NaPCP), and cadmium chloride (Cdd2).  The reference
toxicants may be obtained by contacting the Quality Assurance Branch,
Environmental Monitoring and Support Laboratory, U. S. Environmental
Protection Agency, Cincinnati, Ohio, 4526S; FTS 684-7325, comm'l 513-569-7325.
Instructions for the use and the expected toxicity values for the reference
toxicants are provided with the samples.  To assure comparability of QA
                                      10

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 data on a national scale, all laboratories must use the same source of
 reference toxicant (EMSL-C1ncinnati) and the same formulation of dilution
 water —  moderately hard synthetic water,.described in Table 1, p. 18* for
 fathead minnows and Ceriodaphhia. and algal growth medium described in
 Tables 1 and 2, Section 14, for Selenastrum.

 4.13  FOOD QUALITY

 4.13.1  The quality of the food for fish and invertebrates is an important
 factor in toxicity tests.  Suitable trout chow, Artemia. and other foods
 must be obtained as described in the manual.  Limited quantities of
 reference Artemia cysts, information on commerical sources of good quality
 Artemia cysts,  and procedures for determining cyst suitability as food are
 available from  the Quality Assurance Branch, Environmental Monitoring and
 Support Laboratory, U.  S. Environmental  Protection Agency, Cincinnati,
 Ohio,  45268.  The suitability of each new supply of food must be determined
 in  a side-by-side test  in which the response of test organisms  fed with  the
 new food is  compared with the response of organisms fed a reference food or
 a previously used, satisfactory food.

 4.14  CONTROL CHARTS

 4.14.1   A control  chart should be prepared for  each reference-toxicant-
 organism combination, and successive toxicity values should  be  plotted and
 examined to  determine  if the  results-are within prescribed limits
 (Fig.  1).  In this technique,  a running  plot is maintained for  the toxicity
 values  (Xi) from successive tests with a given  reference toxicant.   The
 type of  control  chart illustrated (USEPA,  1979a)  is  used to  evaluate the
 cumulative trend of the statistics from  a series  of  samples.  The mean (1)
 and  upper and lower control limits (± 2S) are re-calculated  with each
 successive point,  until  the statistics stabilize.   Outliers, which  are
 values which  fall  outside  the  upper  and  lower control limits, and trends of
 increasing or decreasing sensitivity are readily  identified.  At the
 P0.05 probability  level, one  in  20 tests would  be expected to fall
 outside of the control  limits  by chance  alone.

 4.14.2   If the toxicity value  from a given test with the reference  toxicant
 does not fall in the expected  range  for  the  test organisms when using  the
 standard dilution  water, the sensitivity of  the organisms and the overall
 credibility of the  test  system are suspect.  In this case, the test
 procedure should be examined for  defects  and should be repeated with a
 different batch of  test  organisms.

 4.15  RECORD KEEPING

4.15.1  Proper record keeping  is required.  Bound notebooks should be used
to maintain detailed records of the test organisms such as species, source,
 age, date of receipt, and other pertinent information-relating to their
history and health, and  information on the calibration of equipment and
 instruments,  test conditions employed, and test results.  Annotations
should be made on a real-time basis to prevent the loss of information.


                                      11

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              to
              «J
                       UPPER CONTROL LIMIT(X+2S)
                           CENTRALTENOENCY
                       LOWER CONTROL LI MIT (X - 2S)
L I I  I I  I I  I  I  I I  I I  I  I I  I I
                                               •  L
                 OS       10       15       20
                TOXIC1TY TEST WITH REFERENCE TOXICANTS
                                               *»

                    •  Figure 1. Control chart.
                n- I
Where:
    X-f » Successive LCSO's from toxicity tests.
    n 3 Nunier of tests.
  '  X » Mean LC50.
    S » Standard deviation.

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                                   SECTION 5

                           FACILITIES AND EQUIPMENT^


 5.1   GENERAL REQUIREMENTS

 5.1.1  Effluent toxicity tests may be performed in a fixed or mobile
 laboratory.   Facilities should include equipment for rearing, holding, and
 accl-imating  organisms.  Temperature control can be achieved using
 circulating  water baths, heat exchangers, or environmental chambers.  Water
 used for rearing, holding, acclimating, and testing organisms may be ground
 water,  surface water,  dechlorinated tap water, or synthetic water.
 Dechlorination can be  accomplished by aeration (allowing the water to stand
 in an open vessel for  24 h),  carbon filtration, or the use of sodium
 thiosulfate.  Use of 1.0 mg (anhydrous) sodium thiosulfate/L will reduce
 1.5  mg  chlorine/L.  After dechlorination, total residual chlorine should be
 non-detectable.  Air used for aeration must be free of oil and fumes.  Test
 facilities must be well ventilated and free of fumes.   During rearing,
 holding, acclimating,  and testing, test organisms should be shielded from
 external disturbances.

 5.1.2  Materials used  for exposure chambers,  tubing,  etc., which come in
•contact with the effluent should  be carefully chosen.   Tempered glass and
 perfluorocarbon plastics (TEFLONR) should be  used whenever possible to
 minimize sorption and  leaching of toxic substances.  These materials may be
 reused  following decontamination.  Plastics such as polyethylene,
 polypropylene,  polyvinyl  chloride, TY60NR,  etc., may  be used as test
 chambers or  to  store effluents, but caution should be  exercised in their
 use  because  they could introduce  toxicants  when new, or carry over
 toxicants from  one test to another if reused.   The use of glass carboys is
 discouraged  for safety reasons.

 5.1.3  New plastic products of a  type not previously used should be tested
 for  toxicity before initial use by exposing the test organisms in the test
 system  where the material  is  used.  Equipment  (pumps,  valves,  etc.)  which
 cannot  be discarded after each use because  of  cost, must be decontaminated
 according to the cleaning procedures listed below.  Fiberglass,  in addition
 to the  previously mentioned materials,  can  be  used for holding,
 acclimating*  and dilution water storage tanks,  and in  the water delivery
 system.   All  material  should  be flushed or  rinsed thoroughly with the test
 media before using in  the test.   Copper,  galvanized material,  rubber,
 brass,  and lead must not  come in  contact  with  holding,  acclimation,  or
 dilution water,  or with effluent  samples  and test solutions.   Some
 materials, such as several  types  of neoprene rubber (commonly  used for
 stoppers) may be toxic and should be tested before  use.
 1Adapted from: Peltier and Weber  (1985).


                                      13

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5.1.4  Silicone adhesive used to construct glass test chambers absorbs some
organochlorint and organophosphorus pesticides, which are difficult to
remove.  Therefore, as little of the adhesive as possible should be in
contact with water.  Extra beads of adhesive inside the containers should
be removed.

5.2  TEST CHAMBERS

5.2.1  Test chamber size and shape are varied according to size of the test
organism.  Requirements are specified in each test.

5.3  CLEANING

5.3.1  New plasticware used for sample collection or organism exposure
vessels does not require rigorous cleaning.  It is sufficient to rinse the
new containers once with sample before use.  New glassware, however, should
be soaked overnight in acid (see below).

5.3.2  It is recommended that all sample containers, test vessels, pumps,
tanks, and other equipment that has come in contact with effluent be washed
after use in the manner described below to remove surface contaminants.
Special cleaning requirements for glassware used in algal toxicity tests
are described in Section 14.

    1. Soak 15 minutes, and scrub with detergent in tap water, or clean in
       an automatic dishwasher.
    2. Rinse twice with tap water.
    3. Carefully rinse once with -fresh dilute (20% V:V) nitric acid or
       hydrochloric acid to remove scale, metals and bases.  To prepare a
       20X solution of acid, add 20 ml of concentrated acid to 80 mL of
       distilled water.
    4. Rinse twice with tap water.
    5. Rinse once with full-strength acetone to remove organic compounds.
    6. Rinse well with tap water.
    7. Rince twice with dilution water.

5.3.3  All test chambers and equipment must be thoroughly rinsed with the
dilution water immediately prior to use in each test.
                                      14

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                                  SECTION 6

                                TEST ORGANISMS

6.1  SPECIES

6.1.1  The organisms used in the chronic tests described in this manual are
the fathead minnow, (Pimephales promelas), the cladoceran, Ceriodaphnia
dubia, and the green alga, SeTehastrum capricornutum.

6.2  SOURCE

6.2.1  The test organisms are easily cultured in the laboratory.
Culturing, care, and handling procedures for Ceriodaphnia and Selenastrum
are described in the respective test methods sections.  A fathead minnow
culturing procedure using laboratory water is described in Peltier and
Weber (1985).                                .

6.2.2  Starter cultures of Selenastrum capricornutum are available from the
following sources:

    1. Aquatic Biology Section, Biological Methods Branch, Environmental
       Monitoring and Support Laboratory, U.S. Environmental Protection
       Agency, Cincinnati, Ohio  45268.

    2. Environmental Research "Laboratory, U.S. Environmental Protection
       Agency, 200 SW 35th Street, Con/all is, Oregon  97330.

    3* American Type Culture Collection (Culture No. ATCC 22662), 12301
       Parklawn Drive, Rockville, Maryland  10852.

    4. Culture Collection of Algae, Botany Department, University of Texas,
       Austin, Texas 78712.

6.2.3  Starter cultures of the fathead minnow (Pimephales promelas) and
Ceriodaphnia dubia (Berner, 1985) can be obtained from the Aquatic Biology
Section, Biological Methods Branch, EMSL-Cincinnati Newtown Facility,
Environmental Monitoring and Support Laboratory, U. S. Environmental
Protection Agency, Newtown, Ohio  45244  (Phone: FTS 778-8350;
Commercial 513-527-8350).

6.2.4  If because of their source there is any uncertainty concerning the
identity of the organisms, it is advisable to have them examined by a
second party to confirm their identification.
                                      15

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6.3  SHIPMENT ;

6.3.1  Many states have strict regulations regarding the importation of
non-native fishes.  Required clearances should be obtained from state
fisheries agencies before arrangements are made for the interstate shipment
of fathead minnows.                          ;

6.4  DISPOSAL

6.4.1  Test organisms must be destroyed after use.
                                     16

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                                  SECTION 7  "

                                DILUTION WATER

7.1  The source of dilution water used  in the tests will depend  largely on
the objectives of the study as described in  Section 1:   (1)  If the
objective of the test is to estimate the inherent chronic toxicity of the
effluent, a standard dilution water (moderately hard water,  Table 1) is
used;  (2) If the objective of the test is to estimate the chronic toxicity
of the effluent in uncontaminated receiving  water, the test  may  be
conducted using dilution water consisting of a single grab sample of
non-toxic receiving water collected upstream from the outfall, or with
other uncontaminated surface water or standard dilution water having
approximately the same hardness (+; 1056) as the receiving water;  (3) If the
objective of the test is to determine the additive effects of the discharge
on already contaminated receiving water, the test is performed using
dilution water consisting of receiving water collected daily upstream from
the outfal1.                          -

7.2  When the dilution water is to be taken  from the receiving water
"upstream" from the outfall, it should be collected at a point as close as
possible to the outfall, but upstream from or outside of the zone
influenced by the effluent.  The sample should be collected  immediately
prior to the test, but never more than 96 h  before the test  begins.  Except
where it is used within 24 h, the sample should be chilled to 4°C during
or immediately following collection, and maintained at that  temperature
until used.

7.3  Where toxicity-free dilution water is required in a test, the water is
considered acceptable if test organisms show adequate survival,  growth, and
reproduction in the controls during the test.

7.4  Dechlorinated water should be used as dilution water only as a last
resort, because it is usually difficult to completely remove all the
residual  chlorine or chlorinated organics, which may be very toxic to the
test organisms.  Sodium thiosulfate is recommended for dech1orination
(1.0 mg anhydrous sodium thiosulfate/L will  reduce 1.5 mg chlorine/L ).
After dech1 orination, total residual chlorine must be non-detectable.

7.5  If it is necessary to pass the dilution water through a deionizer to
remove unacceptably high concentrations of copper, lead, zinc, fluoride, or
other toxic substances before use, it must be reconstituted to restore the
calcium and magnesium removed by the deiom'zation process.

7.6  To prepare a synthetic fresh water, use the reagents listed in
Table 1.   For example, to prepare 20 L of moderately hard synthetic water:

    1. Place 19 L of distilled or deionized water in a properly cleaned
       plastic carboy.
    2. Add sufficient MgS04, NaHCOs and KC1 to the carboy, and stir
       well.
                                     17

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    3. Add sufficient CaS04.2H20 to 1 L of distilled or deionized
       water in a.separate flask, place on a magnetic stirrer until the
       calcium sulfate has dissolved and add to the carboy and stir well.
    4. Aerate vigorously for 24 h (with air filtered through cotton to
       remove oil) to dissolve the added chemicals and stabilize the
       medium.

7.7  The measured pH, hardness and alkalinity of the aerated water will be
approximately as indicated under "Final Water Quality" in Table 1.
                 TABLE  1.   PREPARATION  OF  SYNTHETIC FRESH WATER4
                  Reagent Added (mg/L)b
Final Water Quality
Water
Type
Very soft
Soft
Moderately
Hard
Very hard
«aHC03 (
12.0
48.0
Hard 96.0
192.0
384.0
AND A • 2Ho
7.5
30.0
60.0
120.0
240.0

7.5
30.0
60.0
120.0-
240.0
KCL
0;5
. 2.0
4.0
8.0
16.0
pHc
6.4-6.8
7.2-7.6
7.4-7.8
7.6-8.0
8.0-8.4
- Alka-
Hardnessd linityd
10-13
40-48
80-100
160-180
280-320
10-13
30-35
60-70
110-120
225-245
aTaken iri part from Marking and Dawson (1973).
bAdd reagent grade chemicals to distilled or deionized water.
cApproximate equilibrium pH after 24 h of aeration.
dExpressed as mg CaC03/L .
                                     18

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                                  SECTION 8

          EFFLUENT AND RECEIVING WATER SAMPLING AND SAMPLE HANDLING

8.1  EFFLUENT SAMPLING

8.1.1  The effluent sampling point usually should be the same as that
specified in the NPOES discharge permit  (USEPA, I979c).  Conditions for
exception would be:   (1) better access to a sampling point between the
final treatment and the discharge outfall; (2)  if the processed waste is
chlorinated prior to  discharge to the receiving waters, it may also be
desirable to take samples prior to contact with the chlorine to determine
toxicity of the unchlorinated effluent;  or (3)  in the event there is a
desire to evaluate the toxicity of the influent to municipal waste
treatment plants or separate wastewater  streams in industrial facilities
prior to their being  combined with other wastewater streams or non-contact
cooling water, additional sampling points may be chosen.

3.1.2  The decision on whether to collect grab  or composite samples is
based on the objectives of the test and  an understanding of the short and
long-term operations  and schedules of the discharger.  If the effluent
quality varies considerably with timet which can occur where holding times
are short, grab samples may seem preferable because of the ease of
collection and the potential of observing peaks (spikes) in toxicity.
However, the sampling duration of a grab sample is so short that full
characterization of an effluent over a 24-h period would require a
prohibitive number of separate samples and tests.  Collection of a 24-h
composite sample, however, may dilute toxicity  spikes, and averages the
quality of the effluent over the sampling period.  A lengthy discussion of
the advantages and disadvantages of using grab or composite samples is
found in Peltier and Weber (1985).

8.1.3  Aeration during collection and transfer of effluents should be
minimized to reduce the loss of volatile chemicals.

8.1.4  Definitive tests performed for NPOES permit purposes require daily
effluent sample collection and daily renewal of test solutions.

8.2  RECEIVING WATER  SAMPLING

8.2.1  It is common practice to collect  grab samples for receiving water
toxicity studies.

8.2.2  When non-toxic receiving water is required for a test, it may be
collected upstream from the outfall or from other uncontaminated surface
water having approximately the same hardness (^ 10%) as the receiving
water.  If the objective of the test is to determine the additive effects
of the discharge on receiving water which may already be contaminated, the
test is performed using dilution water consisting of receiving water
collected daily upstream from the outfall.

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8.2.3  Dilution water to be taken from the receiving water  "upstream" from
the outfall, 1s collected at a point as close  as possible to the outfall,
but upstrean from or outside of the zone influenced by the  effluent.

8.2.4  To determine the extent of the zone of  toxicity in the receiving
water downstream from the outfall, receiving water samples  are collected
at several, distances downstream from the discharge.  The time required for
the effluent-receiving-water mixture to travel to sampling  points
downstream from the outfall may be difficult to ascertain,  and it may not
be possible to correlate downstream toxicity with effluent  toxicity at the
discharge point unless a dye study is performed.  The toxicity of
receiving water samples from five stations downstream from  the discharge
point can be evaluated using the same number of test vessels and test
organisms as used in one effluent toxicity test with five effluent
dilutions.

8.3  SAMPLE HANDLING AND PRESERVATION _

8.3.1 .If the data from the samples are to be  acceptable for use in the
NPDES Program, the lapsed time from collection of a grab or composite
sample and the initiation of the test must not exceed 72 h.  Composite
samples should be chilled during collection, where possible.  Except when
used within 24 h of collection, samples must be chilled after collection
and maintained at 4°C until used.

8.3.2 Samples Used in On-Site Tests

8.3.2.1  Samples collected for on-site tests should be used within 24 h.

8.3.3  Samples Shipped to Off-Site Facilities

8.3.3.1  Samples collected for off-site toxicity testing are to be chilled
to 4°C when collected, shipped iced to the central laboratory, and there
transferred to a refrigerator (4QC) until used.  Every effort must be
made to initiate the-test with an effluent sample on the day of arrival  in
the laboratory.

8.3.3.2  Samples may be shipped in 4-L (1-gal) glass jugs, CUBITAIN£RSR,
or new plastic "milk" jugs.  All sample containers should be rinsed with
source water before being filled with sample.  Glass jugs can be cleaned
and reused (see p. 12), whereas CUBITAINERSR and plastic jugs are not
reused.  Plastic containers used for effluents or toxic surface water
samples should be punctured after use to prevent reuse.

8.4  SAMPLE PREPARATION

8.4.1  With the Ceriodaphnia and fathead minnow tests, effluents and
surface waters must be filtered through a (30 urn) plankton net to remove
indigenous organims that may attack,or be confused with the test organisms
(see Ceriodaphnia test method for details).  Surface waters used in algal
                                     20

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toxicity tests must be filtered through a 0.45 urn pore diameter filter
before use.  It may be necessary to first coarse-filter the dilution
and/or waste water through a nylon sieve having 2- to 4-nro holes to remove
debris and/or break up large floating or suspended solids.

8.4.2  The DO concentration in the dilution water should be near
saturation prior to use.  Aeration will bring the 00 and other gases into
equilibrium with air, minimize oxygen demand, and stabilize the pH.

8.4.3  If the dilution water ana effluent must be warmed to bring them to
the prescribed test temperature, supersaturation of the dissolved gases
may become a problem.  To prevent this problem, the effluent and dilution
water are heated to 25°C and checked for dissolved oxygen (DO) with a
probe.  If the 00 exceeds 8.5 mg/L (100% saturation), the solutions are
aerated virorously with an air stone (usually 1-2 min) until the DO is
lowered to 100% saturation.
                                     21

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                                  SECTION 9  '

              CHRONIC TOXICITY TEST  END POINTS  AND DATA ANALYSIS

 9.1   END  POINTS

 9.1.1   Numerous terms are used to define the end points employed  in
 chronic toxicity tests,  which have  their origin in the earlier, full
 life-cycle tests.   As shorter "chronic" tests  were developed,  it  became
 common  practice to  apply the same terminology  to the end points.  The
 primary terms in current use are listed below:

 9.1.1.1   Safe Concentration  - the highest concentration which  will permit
 normal  propagation  of fish and other  aquatic life in receiving waters.

 9.1.1.2  No Observed Effect  Concentration (NOEC)  - The highest
 concentration of toxicant to which  organisms are exposed in a  full
 life-cycle or partial  life-cycle test,  which causes no statistically
 significant adverse effect on the observed parameters (usually
 hatchability,  survival,  growth,  and reproduction).

 9.1.1.2.   Lowest Observed Effect Concentration  (LOEC)  - The lowest
 concentration  of toxicant to which  organisms are  exposed in a  life-cycle
 or partial  life-cycle test,  which causes  a statistically significant
 adverse effect on the observed parameters (usually hatchability,  survival,
 growth, and reproduction).
                  *

 9.1.1.3.   Maximum Acceptable Toxicant Concentration (MATC) - An
 undetermined concentration within the interval  bounded by the  NOEC and
 LOEC.

 9.1.1.4.   Chronic Value  (ChV)  -  A value lying between  the NOEC and LOEC;
 derived by calculating the geometric mean of the  NOEC  and LOEC.  The term
 is sometimes used interchangably with MATC.

 9.1.1.5.   LC  (or EC)  - Lethal  concentration  (LC)  or effective
 concentration  (EC).  A point estimate of the toxicant  concentration that
would adversely  affect a  given percent  of the test  organisms, calculated
by regression  (such  as Probit Analysis).  The LCI  (or  EC!) is the
estimated concentration of toxicant that adversely  affects 1% of the test
population^ and  is defined here  as the  threshold concentration, or lowest
concentration that would  cause an adverse effect on  the observed
parameters, and falls  in  the range of the NOEC  and  LOEC  (Birge, et.  al.
 1981).

9.2  DATA ANALYSIS

9.2.1  Role of the Statistician

9.2.1.1  The choice of a  statistical method  to  analyze toxicity test data
and the interpretation of the results of the analysis of the data from, any
                                     22

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 of  the  toxicity tests described in this manual can become problematic
 because of the Inherent variability and sometimes unavoidable anomalies in
 biological data.  Analysts  who are not proficient in statistics are
 strongly advised to  seek the assistance of a statistician before selecting
 the method of  analysis and  using any of the results.

 9.2.2   Plotting the  Data

 9.2.2.1   It  is recommended  that the data always be plotted as a
 preliminary  step,  to help spot problems and detect unsuspected trends or
 patterns in  the responses.

 9.2.3   Data  Transformations

 9.2.3.1   Transformations of the data,  such as  arc sine  and logs,  can  be
 used if  they help  the data  meet the assumptions of the  proposed analyses.

 9.2.4  Analysis of Growth and  Reproduction Data

 9.2.4.1   Growth data from the  fathead  minnow larval  survival  and  growth
 test, and reproduction data from the Ceriodaphnia survival  and
.reproduction test, are analyzed using  Dunnett's Procedure (Dunnett, 1955)
 if  the assumptions of normality and homogeneity of variance are met (see
 Appendix  for details).   If  the assumptions are not met, the data  are
 analyzed  using  Steel's Many-One Rank Test  (Steel,  1959; Miller,  1981).

 9.2.4.2   The growth  response data from the algal  toxicity test may be
 converted to a  proportion of the growth of the controls,  which may then be
 analyzed  by Probit Analysis  (Finney, 1971)  or,  the growth response data,
 after an  appropriate transformation  if  necessary  to  meet  the  assumptions
 of  normality and homogeneity of variance,  may  be  analyzed by  Dunnett's
 Procedure or Steel's  Many-One  Rank  Test.

 9.2.5  Analysis of.Mortality Data

 9.2.5.1   Mortality data from the fathead minnow  larval survival and growth
 test and  the fathead  minnow  embryo-larval  survival and teratogenicity test
 are used  in .a Probit  Analysis  to determine  the LCI,  if Probit Analysis  is
 appropriate (see discussion  below).

 9.2.5.2   Fisher's Exact Test is  used to  analyze the mortality data from
 the Ceriodaphnia survival and  reproduction  test, prior to the analysis of
 the reproduction data.

9.2.5.3  Mortality data from the fathead minnow larval survival and growth
test,  and the fathead minnow embryo-larval  survival and teratogenicity
 test,  can be analyzed by Ounnett's Procedure or Steel's Many-One Rank  Test
 after transforming the square root of the proportion of dead organisms to
 an arc  sine value (see Appendix).  This transformation is performed by the
computer program for Dunnett's Procedure provided in the Appendix.
                                     23

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9.2.6  Ounnett's Procedure

9.2.6.1  Dunnett's Procedure consists of an analysis of variance (ANOVA)
to determine the error term, which is then used in a multiple comparison
method for comparing each of the treatment means with the control mean, in
a series of paired tests.  Use of Dunnett's Procedure requires at least
two replicates per treatment.

9.2.6.2  The asumptions upon which the use of Ounnett's Procedure are
contingent are that the observations are independent and normally
distributed, with homogeneity of variance.  Before analyzing the data, the
assumptions are checked using the procedures provided in the Appendix.

9.2.6.3  Some indication of the sensitivity of the analysis should be
provided by calculating: (1) the minimum difference between means that can
be detected as statistically significant, and (2) the percent change from
the control mean that this minimum difference represents for a given
test.  Calculation of beta levels (Type II error, which results when the
null hypothesis is not rejected when it should be) as an indication of the
power of the test would be another alternative.

9.2.6.4  The safe concentration derived from this test is reported in
terms of the NOEC.  A step-by-step example of Dunnett's Procedure is
provided in the Appendix.

9.2.6.5  If, after suitable transformations have been carried out, the
normality assumptions have not been met, the Steel Many-One Rank Test
should be used.   •                      .

9.2.7  Steel's Many-One Rank Test

9.2.7.1  Steel's Many-One Rank Test is a multiple comparison method for
comparing several treatments with a control which is similar to Ounnett's
Procedure, except that it is not necessary to meet the assumption for
normality.  The data are ranked, and the analysis is performed on the
ranks rather than on the data themselves.  If the data are normally or
nearly normally distributed, Dunnett's Procedure would be more sensitive
(would detect smaller differences between the treatments and control).
For data that are not normally distributed, Steel's Many-One Rank Test can
be much more efficient (Hodges and Lehmann, 1956).  It is necessary to
have at least four replicates to use Steel's test.  The sensitivity of
this test cannot be stated in terms of the minimum difference between
treatment means and the control mean.

9.2,7.2  The safe concentration is reported as the NOEC.  A step-by-step
example of Steel's Many-One Rank Test is provided in the Appendix.

9.2.8  Probit Analysis

9.2.8.1  Probit Analysis is used to analyze percentage data from
concentration-response tests.  The analysis can provide an estimate of the


                                     24

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concentration «f toxicant lethal to a giverr percent of the test organisms
and provide a. confidence interval for the estimate.  Probit Analysis also
assumes normal distribution of log tolerances and independence of the
individual, responses.  To use Probit Analysis, at least two partial
mortalities must be obtained.

9.2.9  Fisher's Exact Test

9.2.9.1  Fisher's Exact Test (Finney, 1948; Pearson and Hartley, 1962) is
a statistical method based on-the hypergeometric probability distribution
that can be used to test that the probability of a response is the same in
two binomial populations.  When used with the Ceriodaphnia data, it
provides a conservative test of the equality of any two survival
proportions assuming only the independence of responses from a binomial
population.
                                     25

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                                  SECTION  10

                             REPORT PREPARATION!

    The  following  general format  and content  are  recommended for the
report:

10.1   INTRODUCTION

       1. Permit number
       2. Toxicity  testing requirements of permit
       3. Plant location
       4. Name of receiving water  body
       5. Contractor  (if contracted)
         a. Name of  firm
         b. Phone  number
         c. Address


10.2   PLANT OPERATIONS

       1. Product(s)
       2. Raw materials
       3. Operating schedule
       4. Description of waste treatment
       5. Schematic of waste treatment
       6. Retention time (if applicable)
       7. Volume of waste flow (MGD, CFS, GPM)


10.3   SOURCE OF EFFLUENT (AMBIENT) AND DILUTION WATER

       1. Effluent Samples
         a. Sampling point
         b. Collection dates and times
         c. Sample collection method
         d. Physical and chemical data

      2. Surface Mater Samples
         a. Sampling point
         b. Collection dates and times
         c. Sample collection method
         d. Physical and chemical data
         e. Streamflow (at 7Q10 and at time of sampling)
1Adapted from: Peltier and Weber (1985).  Prepared by Lee Tebo and
William Peltier, Environmental Services Division,  U.  S.  Environmental
Protection Agency, Athens, Georgia.
                                     26

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       3. Dilution Water Samples
          a. Source
          b. Collection date and time
          c. Pretreatment
          d. Physical and chemical characteristics

10.4  TEST METHODS

       1. Toxicity test method used
       2. End point(s) of test
       3. Deviations from reference method, if any, and the reason(s)
       4. Date and time test started
       5. Date and time test terminated
       6. Type of test chambers
       7. Volume of solution used/chamber
       8. Number of organisms/test chamber
       9. Number of replicate test chambers/treatment
      10. Acclimation of test organisms (mean and range)
      11. Test temperature, (mean and range)


10.5  TEST ORGANISMS

       1. Scientific name
       2. Age
       3. Life stage
       4. Mean length and weight (where applicable)
       5. Source
       6. Diseases and treatment (where applicable)


10.6  QUALITY ASSURANCE.

       1. Standard toxicant used and source
       2. Date and time of most recent test
       3. Dilution water used in test
       4. Results (LC50 or,  where applicable,  NOEC and/or EC!)
       5. Physical and chemical methods used


10.7  RESULTS

       1. Provide raw biological  data in tabular  form,  including  daily
          records of affected organisms in each concentration  (including
          controls)
       2. Provide table of LCSO's,  NOECs,  etc
       3. Indicate statistical  methods to  calculate end points
       4. Provide summary table of  physical  and chemical  data
       5. Tabulate QA data
                                    27

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                                 SECTION 11

                               TEST METHOD1.2

    FATHEAD MINNOW (PIMEPHALES PROMELAS) LARVAL SURVIVAL AND GROWTH TEST
                               METHOD 1000.0


1.  SCOPE AND APPLICATION

1.1  This method estimates the chronic  toxicity of whole effluents and
receiving water to the fathead minnow (Pimephales promelas), using newly
hatched larvae in a seven-day, static renewal test".The effects include
the synergistic, antagonistic, and additive effects of all the chemical,
physical, and biological components which adversely affect the
physiological and biochemical functions of the test organisms.

1.2  Detection limits of the toxicity of an effluent or pure substance
are organism dependent.

1.3  Single or multiple excursions in acute toxicity may not be detected
using 24-h composite samples.  Also, because of the long sample
collection period involved in composite sampling, and because the test
chambers are not sealed, highly volatile and highly degradeable toxicants
in the source may not be detected in'the test.


1.4  This method should be restricted to use by or under the supervision
of professionals experienced in aquatic toxicity testing.

2.  SUMMARY OF METHOD

2.1  Larvae (preferrably less than 24-h old) are exposed in a static
renewal system for seven days to different concentrations of effluent or
to receiving water.  Test results are based on the survival and growth
(increase in weight) of the larvae.

3.  DEFINITIONS

    (Reserved for addition of terms at a later date.)

4.  INTERFERENCES

4.1  Toxic substances may be introduced by contaminants in dilution
water, glassware, sample hardware, and testing equipment (see Section 5,
Facilities and Equipment).
     format used for this method was taken from Kbpp, 1983.
2This method was adapted from Norberg and Mount, 1985.
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4.2  Adverse effects of low dissolved oxygen  (DO) concentrations, high
concentrations of suspended and/or dissolved  solids,  and extremes of pH,
may mask the. presence of toxic substances.

4.3  Improper effluent sampling and handling  may adversely affect test
results (see Section 8, Effluent and Receiving Water  Sampling and Sample
Handling). -

4.4  Pathogenic and/or predatory organisms in the dilution water and
effluent may affect test organism survival, and confound test results.

4.5  Food added during the test may sequester metals  and other toxic
substances and confound test results.

5.  SAFETY

5.1  See Section 3, Health and Safety. .

6.  APPARATUS AND EQUIPMENT

6.1  Fathead minnow and brine shrimp culture  units — see Peltier and
Weber (1985).  This test requires 150-300 newly hatched larvae.  It is
preferable to obtain this fish from an inhouse fathead minnow culture
unit.  If it is not feasible to culture fish  inhouse, newly hatched larvae
can be shipped in well oxygenated water in insulated containers.

6.2  Samplers — automatic sampler, preferrably with sample cooling
capability, that can collect a 24-h composite sample of 4 L.

6.3  Sample containers — for sample shipment and storage (see Section 8,
Effluent and Receiving Water Sampling and Sample Handling).

6.4  Environmental chamber or equivalent facility with temperature control
(25+ 2°C).

6.5  Water purification system — Millipore Super-Q or equivalent.

6.6  Balance — analytical, capable of accurately weighing larvae to
0.0001  g.

6.7  Reference weights, Class S ~ for checking performance of balance.
Weights should bracket the expected weights of the weighing pans and the
expected weights of the pans plus fish.

6.8  Test chambers — borosilicate glass or non-toxic disposable plastic
labware.  A minimum of two 1-L beakers are required for each concentration
and control.  To avoid potential  contamination from the air, the chambers
should be covered during the test.

6.9  Volumetric flasks and graduated cylinders — Class A,  borosilicate
glass or non-toxic plastic labware, 10-1000 ml for making test solutions.


                                     29

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6.10  Volumetric pipets-- Class A,  1-100 ml.

6.11  Serological pipets—  1-10 ml, graduated.

6.12  Pipet bulbs and fillers — PropipetR, or equivalent.

6.13  Droppers, and glass tubing with fire polished edges, 4mm  ID — for
transferring larvae.

6.14  Wash bottles — for washing embryos from substrates and containers
and for rinsing small glassware and instrument electrodes and probes.

6.15  Glass or electronic thermometers — for measuring water temperatures.

6.16  Bulb-thermograph or electronic-chart type thermometers — for
continuously recording temperature.

6.17  National Bureau of Standards Certified thermometer (see USEPA Method
170.1, USEPA 1979b).

6.18  pH, DO, and specific  conductivity meters — for routine physical and
chemical measurements.  Unless the test is being conducted to specifically
measure the effect of one of the above parameters, a portable, field-grade
instrument is acceptable.

6.19  Miscellaneous apparatus and equipment — transfer containers, pumps,
and automatic dilution devices should be constructed of materials as
indicated in Section 5, Facilities and Equipment.

7.  REAGENTS AND CONSUMABLE MATERIALS

7.1  Reagent water — defined as activated-carbon-filtered distilled or
deionized water that does not contain substances which are toxic to the
test organisms.  A water purification system may be used to generate
reagent water (see paragraph 6.5 above).

7.2  Effluent, surface water, and dilution water — see Section 7,
Dilution Water, and Section 8, Effluent and Surface Water Sampling and
Sample Handling.

7.3  Reagents for hardness  and alkalinity tests (see USEPA Methods 130.2
and 310.1, USEPA 1979b).

7.4  pH buffers 4, 7, and 10 (or as per instructions of instrument
manufacturer) for standards and calibration check (see USEPA Method 150.1,
USEPA 1979b).

7.5  Membranes and filling  solutions for dissolved oxygen probe (see USEPA
Method 360.1, USEPA 1979b), or reagents for modified Winkler analysis.

7.6  Laboratory quality assurance samples and standards for the above
methods.

                                     30   .

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7.7 •Specific conductivity standards (see USEPA Method 120.T, USEPA 19795).

7.8  Reference toxicant solutions (see Section 4, Quality Assurance).

7.9  Formalin (4%) for use as a preservative for the fish larvae.

7.10  Brine Shrimp (Artemia) Cysts — see Peltier and Weber (1985).

7.10.1  Although there are many commercial sources of brine shrimp eggs,
the Brazilian or Colombian strains are preferred because the supplies
examined have had low concentrations of chemical residues.  (One source is
Aquarium Products, 180 L Penrod Ct., Slen Burnie, MD, 21061).  Each new
batch of Artemia cysts should be evaluated for nutritional suitability
against known suitable reference cysts by performing a larval growth
test..  It is recommended that a sample of newly-hatched Artemia nauplii
from each new batch of cysts be chemically analyzed to determine that the
concentration of total organic chlorine does not exceed 0.15 ug/g wet
weight or the total concentration of organochlorine pesticides plus PCBs
does not exceed 0.3 ug/g wet weight (USEPA, 1982).  If those values are
exceeded, the Artemia should not be used.

7.10.2  Limited quantities of reference Artemia cysts, information on
commerical sources of good quality Artemia cysts, and procedures for
determining cyst suitability are available from the Quality Assurance
Branch, Environmental Monitoring and Support Laboratory, U. S.
Environmental Protection Agency, Cincinnati, Ohio, 45268.

7.11  Test organisms — Newly-hatched fathead minnow larvae (see Peltier
and Weber, 1985).

8.  SAMPLE COLLECTION, PRESERVATION AND STORAGE

8.1  See Section 8, Effluent and Receiving Water Sampling and Sample
Handling..

9.  CALIBRATION AND STANDARDIZATION

9.1. See Section 4, Quality Assurance.

10.  QUALITY CONTROL

10.1  See Section 4, Quality Assurance.

11.  PROCEDURES

11.1  TEST SOLUTIONS

11.1.1  Surface Waters

11.1.1.1  Surface water toxicity is determined with samples used directly
as collected.
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11.1.2  Effluents

11.1.2.1  The selection of the effluent tesl concentrations  should  be
based on the objectives of the study.  One of two dilution factors,
approximately 0.3 or 0.5, is commonly used.  A dilution factor of
approximately 0.3 allows testing between  100% and IX effluent using only
five effluent concentrations (100%, 30%,  10%, 3%, and  1%).   This series of
dilutions minimizes the level of effort,  but because of the  wide interval
between test concentrations provides poor test precision (+  300%).
A dilution factor of 0.5 provides greater precision (+• 1005?), but requires
several additional dilutions to span the  same range oT* effluent
concentrations.  Improvements in precision decline rapidly as the dilution
factor is increased beyond 0.5

11.1.2.2  If the effluent is known or suspected to be  highly toxic, a
lower range of effluent concentrations should be used, beginning at 10%.
If a high rate of mortality is observed during the first 1 to 2 h of the
test, additional dilutions at.the lower range of effluent concentrations
can be added.

11.1.2.3  The volume of effluent required for daily renewal  of two
replicates per concentration, each containing 500 ml of test solution, is
approximately 2 L.  Prepare enough test solution (approximately 1400 mi.)
at each effluent concentration to provide 400 mL additional  volume for
chemical analyses.

11.2  START OF THE TEST

11.2.1  Tests should begin as soon as possible, preferably within 24 h of
sample collection.  If the persistence of the sample toxicity is not
known, the maximum holding time should not exceed 36 h.  In  no case should
the test be started more than 72 h after  sample collection.  Just prior to
testing, the temperature of the sample should be adjusted to (25 +_ 2°C)
and maintained at that temperature until  portions are  added  to the
dilution water.

11.2.2  The test is initiated by placing  larvae one or two at a time, into
each test.chamber in sequential order, until each chamber contains 10
larvae, for a- total of at least 20 larvae for each concentration.  The
test organisms should come from a pool of larvae consisting of at least
three separate spawnings.  The amount of water added to the chambers when
transferring the larvae to the compartments should be kept to a minimum to
avoid unnecessary dilution of the test concentrations.

11.2.3  Randomize the position, of test chambers at the beginning of the
test.

11.3  LIGHT, PHOTOPERIOD AND TEMPERATURE

11.3;1  The light quality and intensity should be at ambient laboratory
levels, which is approximately 10-20 u£/m2/s,  or 50  to 100 foot


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 candles (ft-c),  with a photoperiod of 16 h of light and 8 h of darkness.
 The water temperature in the test chambers should be maintained at
 25 + 2°C.

 11.4  DISSOLVED  OXYGEN (DO)

 11.4.1  Aeration may affect  the toxicity of effluents and should be used
 only as a last resort to maintain satisfactory 00 concentrations.  The 00
 concentrations should not fall  below 40% saturation.  If it is necessary
 to aerate, all concentrations and the control should be aerated.  The
 aeration rate should not exceed 100 bubbles/min,  using a pipet with an
 orifice of approximately 1.5 mm, such as a 1-mL,  Kimax serological pipet,
 No. 37033, or equivalent. Care should be taken to ensure that turbulence
 resulting from aeration does not cause undue physical stress to the fish.

 11.5  FEEDING

 11.5.1'  The fish in each test chamber are fed 0.1 ml (approximately 700 to
 1000) of a concentrated suspension of newly hatched (less than 24-h old)
 brine shrimp nauplii three times daily at 4-h intervals (at the beginning,
 midway, and at the end of the work day).  The nauplii should be rinsed
 with freshwater  before use.

 11.6  DAILY CLEANING OF TEST CHAMBERS .

 11.6.1  Before the .daily renewal of test solutions, uneaten and dead brine
.shrimp and other debris are  removed from the bottom of the test chambers
 with a siphon hose.  Alternately, a large pipet (50 ml) fitted with a
 rubber bulb can  be used.  Because of their small  size during the first few
 days of the tests, larvae are easily drawn into the siphon tube when
 cleaning the test chambers.   By placing the test  chambers on a light box,
 inadvertent removal of larvae can be greatly reduced because they can be
 more easily seen.  If the water siphoned from the test chambers is
 collected in a white plastic tray, the larvae caught up in the siphon can
 be retrieved and returned to the chambers.

 11.7  TEST, SOLUTION RENEWAL

 11.7.1  The test solutions are renewed daily using freshly collected
 samples, immediately after cleaning the test chambers.  The vater level in
 each chamber is  lowered to a depth of 7 to 10 mm, which leaves 15 to 20%
 of the test solution.  New test solution (500 mL) should be added slowly
 by pouring down  the side of  the test chamber to avoid excessive turbulence
 for the larvae.

 11.8  ROUTINE CHEMICAL AND PHYSICAL ANALYSIS

 11.8.1  At a minimum, the following measurements  are made:

 11.8.1.1  DO is  measured at  the beginning and end of each 24-h exposure
 period at all test concentrations and in the control.


                                      33

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11.8.1.2  Temperature, pH, and conductivity,are measured at the beginning
of each 24-h exposure period at aFI test cohcerftrations and in the control.

11.8.1.3  Alkalinity and hardness are measured at the beginning of each
24-h exposure period in 100% effluent and in the control.

11.9  OBSERVATIONS DURING THE TEST

11.9.1  The number of live and dead larvae in each test chamber are
recorded daily, and the dead larvae are discarded.

11.9.2  Protect the larvae from unnecessary disturbance during the test by
carrying out the daily test observations, solution renewals, and removal
of dead larvae, carefully.  Make sure the larvae remain immersed during
the performance of the above operations.

11.10- TERMINATION OF THE TEST      '   •

11.10.1  The test is terminated after seven days of exposure.  At
termination, the larvae in each test chamber are counted and preserved as
a group, in 4% formalin, and are dried and weighed at a later date.
Immediately prior to the dry weight analysis, the preserved larvae are
rinsed in distilled water.  The group of rinsed larvae from each test
chamber are transferred to a tared weighing boat and dried at 100°C for
a minimum of 2 h.  Immediately upon removal from the drying oven, the
weighing boats are placed in a dessicator to prevent the absorption of
moisture from the air, until weighed.  The weights should be measured to
the nearest 0.1 mg.

11.11 ACCEPTABILITY OF TEST RESULTS

11.11.1  For the test results to be acceptable, survival in the controls
must be at least 80%, except where survival in any test concentration is
80% or better.

11.12  SUMMARY OF TEST CONDITIONS

11.12.1  A summary of test conditions  is  listed in Table 1.

12.  CALCULATIONS.

12.1  The endpoints of toxicity tests  using the fathead minnow larvae are
based on the adverse effects on survival  and growth.  Probit Analysis
(Firiney, 1971), Ounnett's Procedure (Dunnett,  1955), and Steel's Many-One
Rank Test (Steel, 1959; Miller, 1981),  are  used to evaluate the data.  See
the Appendix for examples of the manual computations, and the program
listings and examples of  data  input and program output.

12.2  The statistical tests described  here  must be used with a knowledge
of the  assumptions upon which  the  tests are contingent.  Tests for
normality and  homogeneity of variance  are  included in the Appendix.  The
assistance  of  a statistician  is recommended for analysts who are not
proficient  in 'statistics.
                                      34

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 12.3  Table 2  shows  the .survival  and growth response after seven  days  of
 exposure  to the reference toxicant NaPCP.   The data for an effluent would
 be  similar  except'that the test  concentrations would be expressed as a
 percent.

 12.4  Analysis of Survival Data  - Probit Analysis

 12.4.1  Probit Analysis (Finney,  1971)  is  used to  determine the
 concentration  causing  }% mortality (LCI).   In  this analysis,  the  total
 survival  data  from all  test replicates  at  a given  concentration are
 combined  (see  Table  2,  Mean Proportion  Surviving).  A listing of  the
 computer  program and an example  of data input  and  program  output  for the
 Probit Analysis are  provided in  the Appendix.   Note that for  the  data  in
 Table 2,  the number  of  animals exposed  in  each concentration  would be  40,
 and number  that died at each concentration could be calculated from the
 proportions in the table.   The program  transforms  the concentration values
 to  logig  and the percent mortality to probits, and then performs  a
 regression  analysis.

 12.4.2  Report the LCI  and its 95/6 confidence  1-imits.   The LCI is an
 estimate  of the threshold (chronically  toxic)  concentration.  For the
 sample data in Table 2, the LCI  is 128  ug  NaPCP/L, with upper and lower
 95% confidence intervals  of 30.5 .ug/L and  198  ug/L,  respectively.

 12.4.3  If  the data  do  not meet  the assumptions necessary  for the Probit
 analysis, analyze the data using  Dunnett's  Test, as  described below.

 12.5  Analysis of Survival  Data  -  Dunnett's  Procedure

 12.5.1  The survival data meet the normality assumptions (see Appendix),
 which indicates  that analysis b'y  Dunnett's  Procedure is  appropriate.
 If the data had  not  met the assumptions, Steel's Many-One  Rank Test would
 have been used (see  Section 9).   Dunnett's  Procedure (Dunnett, 1955; Steel
 and Torrie,  1960)  includes  an analysis  of  variance (ANOVA), followed by a
 comparison  of  each toxicant concentration mean with  the control mean.  The
 error value  calculated  in  the ANOVA is  used  in the comparison of the
 control and  treatment means.

 12.5.2  It  is  necessary to  have at  least duplicate test chambers at each
 treatment concentration to  perform this test.

 12.5.3  The  computer program listed  in  the Appendix  generates output which
 includes an ANOVA table,  a  statement  about each treatment mean that can be
 used.to identity the NOEC  and LOEC,  and the  minimum  difference between
 treatment and  control means  that can  be detected as  statistically
 significant.

 12.5.4  The  computer program makes  the  necessary transformation of the
 survival data  by converting  the square root  of the proportion of surviving
 organisms to arc sine during the analysis, and includes a special
modification of the arc sine transformation which  is required where the
                                     35

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proportion of surviving organisms  is 0 or  1  (Bartlett,  1937).   For  a more
detailed information on the arc sine transformation,  see  the Appendix.

12.5.5  The results of the analysis of variance  of  the  data from Table  2
are shown in Table 3, and indicate a statistically  significant  difference
in survival among NaPCP concentrations.

12.5.6  The results of the comparison of the control  with the treatment
effects, using 18 degrees of freedom and with  a  Dunnett's "t" value of
2.41 (P » 0.05), indicate that the NOEC is Concentration 5 (256 ug/L) and
the LOEC is Concentration 6 (512 ug/L).  The computer printout  of these
results is as follows:

    THERE IS NO SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 2
    (32 US NAPCP/L) AND CONTROL.

    THERE IS NO SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 3
    (64 UG NAPCP/L) AND;CONTROL.

    THERE IS NO SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 4
    (128 UG NAPCP/L) AND CONTROL.

    THERE IS NO SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 5
    (256 UG NAPCP/L) AND CONTROL.

    THERE IS A SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 6
    (512 UG NAPCP/L) AND CONTROL.

12-.5.7  For this set of data, the minimum difference  that can be detected
as statistically significant is 0.177.  This represents a 19% reduction in
the mean response (survival) from the control.

12.6  The chronic value (ChV) is the geometric mean of the NOEC and LOEC
and is calculated as follows:

    Logic NOEC  =  Logic 256  =  2.4082
    Logic LOEC  =  Logic 512  *  2.7093
    ChV  =  Antilog (2.4082 + 2.7093)/2  =  Antilog 2.5588
    ChV  =  362 ug/L NaPCP

12.7  Analysis of"Growth Data - Dunnett's Procedure

12.7.1   The use of Ounnett's Procedure to analyze the growth data,
expressed in terms of average dry weight (Table 2),  is similar to that for
the survival data, except that the weight data are not transformed.

12.7.2.  The average dry weight of the larvae from each replicate test
chamber (Table 2) is entered into the program.

12.7.3.  The results from the analysis of variance of the data in Table 2
are found in Table 4.   The analysis indicates a statistically significant
difference in the effects on larval growth at the various concentrations
of NaPCP.
                                     36

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 12.7.4.  The results of the comparison  of the  average weights for  each
 treatment with the average weights  for  the control,  using  18 degrees of
 freedom and with, a Dunnett's  "t" value  of 2.41  (P-=  0.05),  indicate that
 the NOEC is Concentration 4 (128 ug NaPCP/L) and  the LOEC  is
 Concentration 5 (256 ug NaPCP/L).   The  computer output from the Ounnett
 program is as follows  (the control  is Concentration  1):

    THERE IS NO SIGNIFICANT DIFFERENCE  BETWEEN  CONCENTRATION 2
    (32 UG NAPCP/L) AND CONTROL.

    THERE IS NO SIGNIFICANT DIFFERENCE  BETWEEN  CONCENTRATION 3
    (64 UG NAPCP/L) AND CONTROL.

    THERE IS NO SIGNIFICANT DIFFERENCE  BETWEEN  CONCENTRATIONS
    (128 UG NAPCP/L) AND CONTROL.

    THERE IS A SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 5
    (256 UG NAPCP/L) AND CONTROL.

    THERE IS A SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 6
    (512 UG NAPCP/L) AND CONTROL.

    For this set of data, the minimum difference  that can be detected as
 statistically significant is 0.095.  This  represents a 13.3% reduction in
 the mean response from the control.

 12.6.5  The chronic value (ChV) is  the  geometric  mean of the NOEC  and LOEC
 and is calculated as follows:

    Logic NOEC  =  Logio 128  =  2.1072
    Log-jo LOEC  *  Logic 256  *  2.4082
    ChV  =  Antilog (2.1072 + 2.40S2)/2  =  Antilog 2.2577
    ChV  «  181 ug/L NaPCP

 12.6.6  The results of the test indicate that growth was a more sensitive
 index of the effects of NaPCP than  was  survival.

 13.  PRECISION AND ACCURACY

 13.1  PRECISION

 13.1.1  Information on the single laboratory precision of the fathead
minnow larval survival and growth test  is presented in Table 5.

 13.2  ACCURACY

 1312.1  The accuracy of toxicity tests can not be determined.
                                     37

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     TABLE 1.  SUMMARY OF RECOMMENDED TEST CONDITIONS FOR FATHEAD MINNOW
               (PIMEPHALES PROMELAS) LARVAL SURVIVAL AND GROWTH TEST
 1. Test type:
 2. Temperature (°C):
 3. Light quality:
 4. Light intensity:
 5. Photoperiod:
 6. Test chamber size:
 7. Test solution volume:
 8. Renewal of test
     concentrations:
 9. Age of test organisms:
10. Larvae/test chamber
     and control:
    Replicate
     chambers/concentration:
11.
12. Feeding regime:
13.
14.
    Cleaning:
    Aeration:
15. Dilution water:

16. Effluent concentrations:
17. Dilution factor:
18. Test duration:
19. Effects measured:
Static renewal
25 + 2°C
Ambient laboratory illumination
10-20 u£/m2/s (50-100 ft-c)(ambient lab
levels)
16 h light, 8 h darkness
1-L containers
500 mL/replicate
Daily
Newly hatched larvaed
10 larvae/chamber;
Minimum of 20 larvae/test concentration
Minimum of 2
Feed 0.1 mL newly hatched brine shrimp nauplii
three times daily, 4 h between feedings (at the
begining, midway, and the end of the work day)
Siphon daily, immediately before test solution
renewal
None, unless DO concentration falls below 4055
saturation.  Rate should be less than 100
bubbles/min.
Moderately hard standard water, receiving
water, other surface water, ground water, or
synthetic water similar to receiving water
At least 5 and a control
Approximately 0.3 or 0.5
7 days
Survival and growth (increase in weight)
                                       38

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       TABLE 3. ANALYSIS OF VARIANCE OF SURVIVAL DATA IN  TABLE  2.
Source
Among
Within
Total
OF
5
18
23
Sum of Squares
1.575
0.426
2.001
Calculated Tabular
Mean Square F ^0.05
0.315 13.3* 2.77
0.024
*
Significant at P s 0.01.
              TABLE 4.  RESULTS FROM ANALYSIS OF VARIANCE OF
                        DRY  WEIGHT DATA  IN TABLE 2.
Source
Among
Within
Total
OF
5
18
23
Sum of Squares
0.155
0.060
0.215
Calculated Tabular
Mean Square F FQ.QS
0.031 9.31* 2.77
0.003

Significant at P  = 0.05
                                    40

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TABLE 5.  PRECISION OF THE FATHEAD MINNOW LARVAL SURVIVAL
          AND GROWTH TEST, USING NAPCP AS A REFERENCE TOXICANT*
NOEC
Test (ug/L)
1 256
2 128
3 256
4 128
5 . 128
6 256
LOEC
(ug/L)
512
256
512
256
256
512
Chronic
Value
(ug/L)
362
181
362
181
181
362
aFor a discussion of the precision of data from chronic toxicity
 tests see Section 4, Quality"Assurance.
                                     41

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           ,  . 	                SECTION 12

                                TEST METHOD1.2

                     FATHEAD MINNOW (PIMEPHALES PROMELAS)
                EMBRYO-LARVAL SURVIVAL AND TERATQGENICITY  TEST
                                METHOD 1001.0

 1.   SCOPE AND APPLICATION

 1.1  This method  estimates  the  chronic toxicity of whole  effluents  and
 receiving water to  the  fathead  minnow (Pimeohales promelas).  using  embryos
 and  larvae  in an  eight-day,  static renewal  test.  The  effects include the
 synergistic, antagonistic,  and  additive  effects of all  the chemical,
 physical, and biological components which adversely  affect the
 physiological and biochemical functions  of  the test  organisms.  The test
 is useful in screening  for  teratogens because organisms are exposed during
 embryonic development.

 1.2  Detection  limits of the toxicity of an effluent or pure  substance are
 organism dependent.

 1.3  Single or  multiple excursions in acute toxicity may  not  be detected
 using 24-h composite samples.   Also,- because  of the  long  sample collection
 period involved in  composite sampling, and  because the  test chambers are
 not  sealed, highly  volatile  and highly degradeable toxicants  in the source
 may  not be detected  in  the-test.

 1.4  This method  should be restricted to use  by or under  the  supervision
 of professionals  experienced in aquatic  toxicity testing.

 2.   SUMMARY OF  METHOD

 2.1  Fathead minnow embryos  and larvae are  exposed in a static renewal
 system, from shortly after fertilization  of the eggs through  four days
 posthatching (total of  eight days),  to different concentrations of
 effluent or to  receiving water.  Test results  are based on the total
 frequency of both mortality  and gross morphological  deformities (terata).

3.  DEFINITIONS

     (Reserved for addition of terms  at a  later date.)

4.  INTERFERENCES

4.1  Toxic substances may be introduced by contaminants in dilution water,
 glassware, sample hardware,  and testing equipment (see -Section 5,
Facilities and  Equipment).
     format used for this method was taken from Kopp, 1983.
2This method was adapted from Birge and Black, 1981.
                                     42

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4.2  Adverse effects of low dissolved oxygen (DO), high concentrations of
suspended and/or dissolved solids, and extremes of pH may mask the
presence of toxic substances.

4.3  Improper effluent sampling and handling may adversely affect test
results (see Section 8, Effluent and Receiving Water Sampling and Sample
Handling).-

4.4  Pathogenic and/or predatory organisms in the dilution water and
effluent may affect test organism survival, and confound test results.

5.  SAFETY

5.1  See Section 3, Health and Safety.

6.  APPARATUS AND EQUIPMENT

6.1  Laboratory fatheadl minnow and brine shrimp culture units — See
Peltier and Weber, 1985.  To test effluent toxicity on-site or in the
laboratory, sufficient numbers of newly fertilized eggs must be available,
preferably from a laboratory fathead minnow culture unit.  If necessary,
embryos can be shipped in well oxygenated water in insulated containers.

6.2  Samplers — automatic sampler, preferrably with sample cooling
capability, that can collect a 24-h composite sample of 2 L.

6.3  Sample containers — for sample shipment and storage (see Section 8,
Effluent and Receiving Water Sampling and Sample Handling).

6.4  Environmental chamber or equivalent facility with temperature control
(25± 2°C).

6.5  Water purification system — Millipore Super-Q or equivalent.

6.6  Balance — analytical, capable of accurately weighing 0.0001 g.

6.7  Reference weights, Class S — for checking performance of balance.

6.8  Test chambers — borosilicate glass or non-toxic plastic labware; a
minimum of two 500 mL beakers or deep petri dishes with covers per test
concentration.  The chambers should be covered during the test to avoid
potential contamination from the air.  Care must be taken to avoid
inadvertently removing.embryos or larvae when test solutions are decanted
from the'Chambers.  The covers are removed only for observation and
removal of dead organisms.

6.9  Dissecting microscope, or long focal length magnifying lens, hand or
stand supported — for examining embryos and larvae in the test chambers.

6.10  Light box, microscope lamp, or flashlight — for illuminating
embryos and chambers during examination and observation of embryos and
larvae.

                                     43

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 6.11   Volumetric flasks and graduated cylinders — Class A,  borosillcate
 glass  or  non-toxic plastic labware,  10-1000 ml, for making test solutions.

 6.12   Volumetric pi pets— Class A,   1-100 ml.

 6.13   Serological  pi pets— 1-10 ml,  graduated.

 6.14   Pipet  bulbs  and fillers  — PropipetR, or  equivalent.

 6.15   Droppers,  and glass tubing with fire polished edges, 2 -mm ID —  for
 transferring embryos, and 4-mm ID — for transferring  larvae.

 6.16   Wash bottles ~ for washing embryos from  substrates and containers
 and for rinsing  small glassware and  instrument  electrodes and probes.

 6.17   Glass  or electronic thermometers — for measuring  water temperatures.

 6.18   Bulb-thermograph or electronic-chart type thermometers —  for
 continuously recording temperature.

 6.19   National Bureau of  Standards Certified thermometer (see EPA  Method
 170.1, USEPA 1979b).

 6.20   pH, 00, and  specific conductivity meters  —  for routine physical and
 chemical measurements.  Unless  the tes't is  being conducted to specifically
 measure the  effect of one of the above parameters,  a portable, field-grade
 instrument is -acceptable.
 lS' JS1*iseetl«!wbos "apparatus and equipment — transfer containers, pumps,
and automatic dilution devices should be constructed of materials as
indicated in Section 5, Facilities and Equipment.

7.  REAGENTS AND CONSUMABLE MATERIALS

7.1  Reagent water — defined as carbon-filtered distilled or deionized
water which does not contain substances which are toxic to the test
organisms.  A water purification system may be used to generate reagent
water (see paragraph 6.5 above).

7.2  Effluent, surface water, and dilution water — see Section 7,
Dilution Water, and Section 8, Effluent and Surface Water Sampling and
Sample Handling*

7.3  Reagents; for; hardness and alkalinity tests (see EPA Methods 130.2 and
310.1, USEPA T979b|.

7.4  pH buffers 4, 7, and 10 (or as per instructions of instrument
manufacturer) for standards and calibration check (see USEPA Method 150.1,
USEPA 1979b).

7.5  Membranes and filling solutions for dissolved oxygen probe (see USEPA
Method 360.1, USEPA 1979b), or reagents for modified Winkler analysis.

                                     44

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7.6  Laboratory quality assurance samples and standards for the above
methods.

7.7  Specific conductivity standards (see EPA Method 120.1, USEPA 1979b).

7.8  Reference toxicant solutions (see Section 4, Quality Assurance).

7.9  Test Organisms — fathead minnow embryos, .2- to 24-h old (preferably
less than 12-h old), and spawned over less than an 8-h period, are used
for the test (for fathead minnow culturing methods (Peltier and Weber,
1985).  Spawning substrates with the newly-spawned, fertilized embryos are
removed from the spawning tanks or ponds, and the embryos are separated
from the spawning substrate by using the index finger and rolling the
embryos gently with a circular movement of the finger (See Gast and
Brungs, 1973).  The embryos are then washed from the spawning substrate
into a petri dish, using the spray from a wash bottle filled with fresh
culture water, and are examined using a dissecting microscope or other
suitable magnifying device.  Damaged and infertile eggs are discarded.  It
is strongly recommended that the embryos be obtained from fish cultured
inhouse, rather than from outside sources, to eliminate the uncertainty of
damage caused by shipping and handling that may not be observable, but
which might affect the results of the test.  ..

7.9.1  The embryos from several substrates are then pooled in a single
container to provide a sufficient number to conduct the required number of
tests.  These embryos may be used immediately to start a test or may be
placed in a suitable container and transported for use at a remote
locationt  When overnight transportation is required, embryos should be
obtained when they are 6- to 8-h old.  This permits the tests at the
remote site to be started with less than 24-h old embryos.  Embryos should
be transported or. shipped in clean, opaque, insulated containers, in well
aerated or oxygenated fresh culture or dilution water, and should be
protected from extremes of temperature and any other stressful conditions
during transport.  Instantaneous changes of water temperature when embryos
are transferred from culture unit water to test dilution water, or from
transport container water to on-site test dilution water, should be less
than 2°C.  Instantaneous changes of pH, dissolved ions, osmotic
strength, and DO should also be kept to a minimum.

7.9.2  The number of embryos needed to start the test will depend on the
number of tests to be conducted and the objectives.  The test is usually
conducted with at least duplicate test chambers at each toxicant
concentration and in the control.  At least 40 embryos are exposed per
test concentration (20 embryos in each of duplicate test chambers),
although a larger number, such as 100 (50 embryos in each of duplicate
test chambers), will provide better precision.  If fewer than 40 embryos
are used per concentration, test precision will be significantly reduced.
Using more than 100 embryos per test concentration will not provide
sufficient advantage to offset the increased time and effort required for
observation and counting and removal of dead embryos during the test.  The
use of 50 embryos per replicate and TOO embryos per test concentration
(a total of 600 embryos for five test concentrations and a control) is
considered optimal.
                                     45

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8.  SAMPLE COLLECTION, PRESERVATION AND HANDLING

8.1  See Section 8, Effluent and Receiving Water Sampling and Sample
Handling.

9.  CALIBRATION AND STANDARDIZATION

9.1  See Section 4, Quality Assurance.

10.  QUALITY CONTROL

10.1  See Section 4, Quality Assurance.

11.  PROCEDURES

11.1  TEST SOLUTIONS

11.1.1  Surface Waters ;  .    -

11.1.1.1  Surface water toxicity is determined with samples used directly
as collected.                                                        -

11.1.2  Effluents                       .     '

11.1.2.1  The selection of the effluent test concentrations should be
based on the objectives of the study.  One of two dilution factors,
approximately 0.3 or 0.5, is commonly used.  A dilution factor of
approximately 0.3 allows testing between 100% and 1% effluent using only
five effluent concentrations (100%, 30%, 10%, 3%, and 1%).  This series of
dilutions minimizes the level of effort, but because of the wide interval
between test concentrations provides poor test precision (+ 300%).
A dilution factor of 0.5 provides greater precision (+ 100%), but requires
several additional dilutions to span the same range oT effluent
concentrations.  Improvements in precision decline rapidly as the dilution
factor is increased beyond 0.5

11.1.2.2  If the effluent is known or suspected to be highly toxic, a
lower range of effluent concentrations should be used (such as 10%, 3%,
1%, 0.3%, and 0.1%).  If a high rate of mortality is observed during the
first 1 to 2 h of the test, additional dilutions at the lower range of
effluent concentrations can be added.

11.1.2.3  The volume of effluent required for daily renewal of two
replicates per concentration, each containing 400 mL of test solution, is
approximately 2 L.  Prepare enough test solution (approximately 1200 mL)
at each effluent concentration to provide 400 mL additional volume for
chemical analyses.

11.1.2.4 The hardness of the test solutions must exceed 25 mg/L
to insure hatching success.
                                     46

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 11.2   START OF  THE TEST

 11.2.1  Tests should begin as  soon as  possible,  preferably within 24 h of
 sample collection.  If the persistence of the sample toxicity is  not
 known, the maximum holding time should not exceed  36 h.   In no case should
 the test be started more than  72 h after sample  collection.  Oust prior to
 testing, the temperature of the sample should be adjusted to 25 + 2°C
 and maintained  at  that temperature until  portions  are added to tFe
 dilution water.

 11.2.2  Gently  agitate and mix the embryos to be used in  the test in a
 large  container so that eggs from different spawns are evenly dispersed.

 11.2.3  Randomly add the embryos to each test chamber.  Accomplish this by
 adding a small  number of embryos (5 to 15)  to test chambers selected in a
 random fashion  using a small bore (2mm)  glass tube calibrated to  contain
 approximately the  desired number of embryos.   Repeat the  process  until  the
 appropriate number of embryos, have been  added to each chamber.
 Alternately, the total  number  of embryos  are  added at the same time to
 randomly selected  test chambers.

 11.2.4  After the  embryos have been distributed  to each test chamber,
 examine and count  them.   Remove and discard damaged or infertile  eggs  and
 replace with new undamaged embryos.  It may be more convenient and
 efficient  to transfer embryos  to intermediate containers  of dilution water
 for examination  and counting.   After the  embryos have been  examined  and
 counted in the  intermediate container, assign them to the appropriate test
 chamber and transfer them with a minimum  of dilution  water.   If ntore than
 one test is being  performed, the exposure is  started  for  all  of the tests
 at approximately the same time.

 11.2.5   Randomize  the position of the  test  chambers  at the  beginning of
 the test.

 11.3   LIGHT, PHOTOPERIOD  AND TEMPERATURE

 11.3.1  The  light  quality and  intensity should be  at  ambient  laboratory
 levels,  approximately 10-20 uE/m2/s, or 50  to  100 foot candles (ft-c),
with a  photoperiod  of 16  h  of  light  and 8 h of darkness.  The test water
temperature  should  be maintained  at  25 + 2°C.

 11.4  DISSOLVED OXYGEN (DO)

11.4.1  Aeration may affect the toxicity of effluents and should be used
only as a  last resort to maintain  satisfactory DO concentrations.   The DO
concentrations should not fall below 40% saturation.  If  it is necessary
to aerate, all  concentrations  and the control should be aerated.  The rate
should not exceed  100 bubbles/min, using a pipet with a 1-2 mm orifice,
such as a  1-mL Kimax Serological Pipet No. 37033, or equivalent.  Care
should be taken to  ensure that turbulence resulting from the aeration does
not cause undue physical  stress to the fish.


                                     47

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11.5  FEEDING   "
               :-'":;.                   .:,         •'•*  -t
11.5.1  Since feeding 1s not required, It Is  not necessary to clean the
test chambers daily.

11.6  TEST SOLUTION RENEWAL

11.6.1  The test solutions are renewed dally  using freshly collected
samples, Immediately after cleaning the test  chambers.  During the dally
renewal process 7-10 mm of water Is left In the chamber to ensure that the
embryos and larvae remain submerged during the renewal process.  New test
solution (400 mL) should be added slowly by pouring down the side of the
test chamber to avoid excessive turbulence for the larvae.

11.7  ROUTINE CHEMICAL AND PHYSICAL DETERMINATIONS

11.8.1  At a minimum, the following measurements are made:

11.8.1.1  DO Is measured at the beginning and end of each 24-h exposure
period at all test concentrations and In the  control.

11.8.1.2  Temperature, pH, and conductivity are measured at the beginning
of each 24-h exposure period at all test concentrations and in the control.

11.8.1.3  Alkalinity and hardness are"measured at the beginning of each
24-h exposure period in 100% effluent and in  the control.
                     r
TT.8  OBSERVATIONS DURING THE TEST

11.8.1  At the end of the first 24 h of exposure, before renewing the test
solutions, examine and count the embryos.  Remove the dead embryos (milky
colored and opaque) and record the number.  If the rate of mortality or
fungal infection exceeds 20% in the control chambers, or if excessive
non-concentration-related-mortality occurs, terminate the test and start a
new test with new embryos.  If the above mortality conditions do not
occur, continue the test for the full eight days.

11.8.2  At 25°C, hatching begins on about the fourth day.  After
hatching begins, count the number of dead and live embryos and the number
of hatched, dead, live, and deformed larvae, daily.  Deformed larvae are
those with gross morphological abnormalities  such as lack of appendages,
lack of fusiform shape (non-distinct mass), lack of mobility, a colored,
beating heart in an opaque mass, or other characteristics that preclude
survival.  Remove dead embryos and larvae as  previously discussed and
record the numbers for all of the test observations (see sample data
record in Table 1 below).

11.8.3  Protect the embryos and larvae from unnecessary disturbance during
the test by carrying out the daily test observations, solution renewals,
and removal of dead organisms, carefully.  Make sure the test organisms
remain immersed during the performance of the above operations.

                                     48

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n.9  TERMINATION OF THE TEST

11.9.1  The tist is terminated after eight days of exposure.  Count the
number of surviving, dead, and deformed larvae, and record the numbers of
each.  The deformed larvae are treated as dead.  Keep a separate record of
the total number of deformed larvae for use in reporting the
teratogenicity of the test solution.

11.10 ACCEPTABILITY OF TEST RESULTS

11.10.1  For the test results to be acceptable, survival in the controls
must be at least 80%, except where survival in any test concentration is
80% or better.

11.11 SUMMARY OF TEST CONDITIONS

11.11..1  A summary of test conditions is listed in Table 1.

12.  CALCULATIONS

12.1  The endpoints of this toxicity test are based on the effects on
survival and occurrence of terta.  Table 2 shows the data on survival and
deformaties after eight days of exposure.to trickling filter waste.

12.2  The mortality data are analyzed-using Probit Analysis (Finney,
1971), Dunnett's Procedure (Dunnett, 1955), or Steel's Many-One Rank Test
(Steel, 1959; Miller, 1981).

12.3  The statistical tests described here must be used with a knowledge
of the assumptions upon which the tests are contingent.  Dunnett's
Procedure is used when the tests for the assumptions described in the
Appendix are satisfied.  If the assumptions are not met, Steel's Many-One
Rank Test may be more appropriate, but the advice of a statistician should
be sdught.

12.4  Data Preparation

12.4.1  Total mortality (combined total number of dead embryos,  dead
larvae, and deformed-larvae) has been found to be the most sensitive
endpoint.  Tabulate and summarize the data and combine the number of dead
embryos, dead larvae, and deformed larvae at each concentration.  Total
mortality is expressed as the mortality proportion, and can be determined
by dividing the total mortality by the number of live embryos at the
beginning of the test.

12.5  DATA ANALYSIS

12.5.1  Probit Analysis

12.5.1.1  Probit Analysis is used to determine the concentration causing
1% mortality.  In this analysis,  the mortality data from the test
replicates at a given concentration are combined (see Table 28).

                                     49

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The program.transforms the concentration values to log-jo and the percent
mortality to probits, and then performs a regression analysis.  A  listing
of the computer program and an example of data input and program output
for the Probit Analysis are provided in the Appendix.

12.5.1.2  Report the LCI and its 95% confidence limits.  The LCI is an
estimate of the threshold (chronically toxic) concentration.  For  the
sample data in Table 2, the LCI is 4.7% effluent, with upper and lower 95%
confidence intervals of 5.6% and 3.6% effluent, respectively.

12.5.1.3  If an LCI can not be calculated using Probit analysis, analyze
the data using Dunnett's Procedure, as described below.

12.5.2  Dunnett's Procedure

12.5.2.1  Dunnett's Procedure includes an analysis of variance (ANOVA)
followed by a comparison of each toxicant concentration mean with the
control mean.  The error value calculated in the ANOVA is used in the
comparison of the control and treatment means.  An example of Dunnett's
Procedure is included in the Appendix.  The computer program listed in the
Appendix generates output that includes an ANOVA table, a statement about
each treatment mean that can be used to identify the NOEC, and the minimum
difference between treatment and control means that can be detected as
statistically significant.

12.5.2.2  It is necessary to have at least duplicate test chambers at each
treatment concentration to carry out Dunnett's Procedure.  With Steel's
Many-One Rank Test,'it is necessary to have at least four replicates per
treatment.

12.5.2.3  The computer program makes the necessary transformation of the
survival data by converting the square root of the proportion of surviving
organisms to arc sine during the analysis, and includes a special
modification of the arc sine transformation which is required where the
proportion of surviving organisms is 0 or 1 (Bartlett,  1937).  For a more
detailed information on the arc sine transformation see the Appendix.

12.5.2.4  The results of the computer analysis of the data in Table 2A
using by Dunnett's Procedure is provided below.  The results of the
analysis of variance are shown in Table 3, and indicate a statistically
significant difference in survival among effluent concentrations.  The
results of the comparisons of the control  mean with the treatment means is
as follows:

   THERE IS NO SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 2
   (3% EFFLUENT) AND CONTROL.

   THERE IS NO SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 3
   (5% EFFLUENT) AND CONTROL.

   THERE IS NO SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 4
   (7% EFFLUENT) AND CONTROL.

                                    50

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    THERE  IS A SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION  5
    (11X EFFLUENT) AND CONTROL.

    THERE  IS A SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION  6
    (16% EFFLUENT) AND CONTROL.

 12.5.2.5   Report the NOEC and LOEC.   For the set  of  data  analyzed, the
 NOEC  is 7% effluent  and  the LOEC  is  11* effluent.

 12.5.2.6   For this set of data, the  minimum  difference that can be
 detected  as statistically significant is 0.2385.  This represents a 28.7%
 change  in the response from the control.

 12.5.3  The chronic  value (ChV) is the geometric mean of  the NOEC and LOEC
 and is  calculated as follows:

    Log-jo NOEC *  Logib  7.0 - =   0.8451
    Log-|Q LOEC »  Logio  11.0 *   1.0414
    ChV   » Antilog  (0.8451 + 1.0414)/2   *  Antilog  0.9432
    ChV   * 8.8% effluent

 13.  PRECISION AND ACCURACY     ''"...-

 13.1 PRECISION

 13.1.1  Data  shown in  Tables 4 and 5  indicate that the precision-of the
 embryo-larval  survival and teratogenicity test, expressed as the relative
 standard  deviation (or coefficient of  variation, CV) of the LCI values,
was 62% for cadmium  (Table 4), and 41% for Diquat (Table 5).

 13.1.2  Precision data are also available from four embryo-larval  survival
 and teratogenicity tests on trickling  filter pilot plant effluent
 (Table 6).  Although the data could not  be analyzed by Probit Analysis,
the NOECs  and LOECs obtained using Dunnett's Test were the same for all
four tests, 7% and 11% effluent, respectively, indicating maximum
precision  in terms of the test design.

13.2 ACCURACY

13.2.1  The accuracy of toxicity tests cannot be determined.

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        TABLEMv SUMMARY OF RECOMMENDED TEST CONDITIONS FOR THE FATHEAD
                 MINNOW (PIMEPHALES PRQMELAS) EMBRYO-LARVAL SURVIVAL AND
            — - TERATOSENICITY TEST
 1. Test type:
 2. Temperature:
 3. Light quality:
 4. Light Intensity:
 5. Photoperiod:
 6. Test chamber size:
 7. Test solution volume:
 8. Renewal of test concentration:
 9. Age of test organisms:
10. No. of embryos/chamber:
11. Replicate test
    chambers/concentrat1on:
12. Embryos per concentration:
13. Feeding regime:
14. Aeration:
15. Dilution water:

16. Effluent test concentrations:
17. Dilution factor:
18. Test duration:
19. Effects measured:
Static renewal
25 + 2°C
Ambient laboratory  light
10-20 uE/ra2/s, or 50-100 ft-c  (ambient
laboratory  levels)
16 h light, 8 h dark
500- mL
400 mL
Daily
2- to 24-h old embryos; preferably less
than 12-h old
20 to 50
2

40 to 100
Feeding not required
None unless DO falls below 40% saturation
Hardness greater than 25 mg/L (CaCOs);
receiving water or other surface water,
ground water, or synthetic water if
similar to receiving water
5 and a control
Approximately 0.3 or 0.5
8 days
Percent hatch,  percent larvae with terata,
percent of normal  larvae surviving 4  days
post-hatch;  surviving normal larvae from
original  embryos
                                       52

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      TABLE 2. DATA FROM FATHEAD MINNOW EMBRYO-LARVAL TOXICITY
               TEST WITH TRICKLING FILTER WASTE
        A. REPLICATES A AND B (USED IN DUNNETT'S PROCEDURE)
Repl. Effl. No. Dead at
Cone. Eggs at Hatching
(51) Start No. (%)
A Cont.
3
5
7
. n
16
B Cont.
3
5
7
n
16
51
50
52
50
50
49
49
50
50
50
49
50
5
5
5
2
10
39
9
6
10
6
30
29
10
10
10
4
20
80-
18
12
20
12
61
58
Dead + Deform.
at hatching
No. (%)
6
5
6
8
25 .
39
9
6
10
10
37-
34
12
10
12
16
50
80
18
12
20
20
76
68
Dead at Test
Termination
No. (%)
6
5
5
9
17
49
10
9
10
16
33
45
12
10
10
18
34
100
20
18
20
32
66
90
Dead + Deform.
at termination
No. (%)
7
5
6
15
32
49
10
. 9
10
20
40
50
14
10
12
. 30
64
100
20
18
20
40
82
100
B. COMBINED DATA FROM REPLICATES A AND B (USED IN PROSIT ANALYSIS)
Repl.
A&B
Effl. No.
Cone. Eggs at
(%) Start
Cont.
3
5
7
n
16
100
100
102
100
99
99
Dead at Dead + Deform.
Hatching at hatching
' No. (X) No. (X)
14
11
15
a
40
68
14
11
15
8
40
69
15
11
16
18
62
73
15
11
16
18
62
74
Dead at Test Dead + Deform.
Termination at termination
No. (%) No. (%)
16
14
15
25
50
94
16
14
15
25 •
50
95
17
14
16
35
72
99
17
14
16
35
73
100
                                 53

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   TABLE 3. ANALYSIS OF VARIANCE TOTAL MORTALILTY DATA IN TABLE 2A,  BASED
            ON THE PROPORTION OF DEAD AND DEFORMED ORGANISMS IN REPLICATES
            A AND B AT TEST TERMINATION
Source
Among
Within
Total '
OF
5
6
11
Sum of Squares
2.089
0.043
2.132 . -
Mean Square
0.418
0.007
-
Calculated Tabular
58.80* 4.39

Significant at P = 0.05.
                                    54

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  TABLE-4. PRECISION OF THE FATHEAD MINNOW EMBRYO-LARVAL
           SURVIVAL AND TERATOGENICITY TEST, USING CADMIUM
           AS A REFERENCE TOXICANT3*0
Test
1
2
• 3
4
5
N
Mean
SD
- CV(X)
LCic 95% Confidence
(mg/L) Limits
0.014 0.009 - 0.018
0.006 0.003 - 0.010
0.005 . 0.003 - 0.009
0.003 0.002 - 0.004
0.006 0.003 - 0.009
5
0.0068
0.0042
' 62
NOEC<*
(mg/L)
0.012
0.012
0.013
0.011
0.012

aTests conducted by Drs. Wesley Birge and Jeffrey Black,
 University of Kentucky, Lexington, under a cooperative
 agreement with the Aquatic  Biology Section, Environmental
 Monitoring and Support Laboratory, U.S. Environmental
 Protection Agency, Cincinnati, Ohio  (Cornelius I. Weber,
 Project Officer).

^Cadmium chloride was used as the reference toxicant.
 The nominal concentrations, expressed as.cadmium (mg/L), were:
 0.01, 0.032, 0.100, 0.320, and 1.000.  The water hardness was
 100 mg/L as calcium carbonate.'

C0etenained by Probit Analysis.

dHighest no-observed-effect concentration determined
 by independent statistical analysis (2x2 Chi-square Fisher's
 Exact Test).
                              55

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TABLE 5. PRECISION OF THE FATHEAD MINNOW, EMBRYO-LARVAL,
         SURVIVAL AND TERATOGENICITY TOXICITY TEST, USING
         DIQUAT AS A REFERENCE TOXICANT*
Test

1
2
3 : , - .
. 4
5
N
Mean
SO
CV(*) ;
LClb
(mg/L)
0.58
2.31
1.50
1.71
1.43
"5
1.51
0.62
41.3
95% Confidence
Limits
0.32 - 0.36
c
1.05 - 1.87
1.24 - 2.09
0.93 - 1.83




 aTests conducted by Drs.  Wesley Birge and Jeffrey Black,
  University of Kentucky,  Lexington,  under a cooperative
  agreement with the Aquatic Biology  Section,  Environmental
  Monitoring and Support Laboratory,  U.S.  Environmental
  Protection Agency, Cincinnati, Ohio (Cornelius  I.  Weber,
  Project Officer).

 ^Determined by Probit analysis.

 cNot calculatable.
                          56

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TABLE 6. PRECISION OF FATHEAD MINNOW EMBRYO-LARVAL
         SURVIVAL AND TERATOGENICITY STATIC-RENEWAL
         TEST CONDUCTED WITH TRICKLING FILTER EFFLUENTa»b

Test
No.
1
2
3
4

NOEC
(% Effl)
7
. 7
7
7

LOEC
(X Effl)
11
11
11
11
   aEffluent concentrations used:  3, 5, 7, 11
    and 16%.
   ^Maximum precision achieved in terms of
    NOEC-LOEC interval.  For a discussion of the
    precision of data from chronic toxicity tests
    see Section 4, Quality Assurance.
                       57

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                                 SECTION  13

                                TEST METHOD1.2

                 CERIOOAPHNIA SURVIVAL AND REPRODUCTION TEST
                                METHOD 1002.0


 1.   SCOPE AND APPLICATION

 1.1   This method measures the chronic toxlcity of whole  effluents  and
 receiving water to the cladoceran,  Ceriodaphnia dubla. during a seven-day,
 static  renewal  exposure.   The effects include the synergistic,
 antagonistic, and additive effects  of all the chemical,  physical,  and
 biological  components  which adversely affect the physiological  and
 biochemical  functions  of  the test organisms.

 1.2   Detection  limits  of  the toxicity of  an  effluent  or  pure  substance  are
 organism  dependent.

 1.3   Single  or  multiple excursions  in acute  toxicity  may not  be detected
 using 24-h composite samples.  Also,  because of the long sample collection
 period  involved in composite sampling and because the test chambers are
 not  sealed,  highly volatile and highly degradeable toxicants  in the source
 may  not be detected in the test.
                   -f

 1.4   This method should be restricted to  use by or under the  supervision
 of professionals experienced in aquatic toxicity testing.

 2.   SUMMARY  OF  METHOD

 2.1   Ceriodaphnia  are  exposed in a  static renewal  system for  seven days to
 different concentrations  of effluent, or  to  receiving water.  Test results
 are  based on  survival  and  reproduction.   If  the  test  is conducted as
 described, the  control  organisms should produce  three broods  of young
 during the seven-day period-

 3.   DEFINITIONS

     (Reserved for  addition  of terms at a  later date.)

4.   INTERFERENCES

4.1  Toxic substances may be introduced by contaminants in dilution water,
 glassware, sample hardware, and testing equipment  (see Section 5,
Facilities and  Equipment).
     format used for this method was taken from Kopp, 1983.
2This method was adapted from Norberg and Mount, 1984.
                                     58

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4.2  Improper effluent sampling and handling may adversely affect test
results (see Section 8, Effluent and Receiving Water Sampling and Sample
Handling).

4.3  Pathogenic and/or predatory organisms in the dilution water and
effluent may affect test organism survival, and confound test results.

4.4  The amount and type of natural food in the effluent or dilution
water may confound test results.

4.5  Food added during the test may sequester metals and other toxic
substances and confound test results.

5.  SAFETY

5.1  See Section 3, Health and Safety.

6.  APPARATUS AND EQUIPMENT   '

6.1  Laboratory Ceriodaphnia culture unit — See culturing methods
below.  To test effluent or receiving water toxicity, sufficient numbers
of newborn (neonate) organisms must be available.

6.2  Samplers — Automatic sampler, preferrably with sample cooling
capability, capable of collecting a 24-h composite sample of 1 L.

6.3  Sample containers. — for sample shipment and storage (See Section 8,
Effluent and Receiving Water Sampling and Sample Handling).

6.4  Environmental chamber, incubator, or equivalent facility with
temperature control (25+ 1°C).

6.5  Water purification system — Millipore Super-Q or equivalent.

6.6  Balance — Analytical, capable of accurately weighing 0.0001 g.

6.7  Reference weights, Class S — for checking performance of balance.

6.8  Racks for test vessels — Racks approximately 8 cm x 40 cm, drilled
to hold 10 test vessels each.

6.9  Dissecting microscope — for examining organisms in the test
chambers.

6.10  Light box — for illuminating organisms during examination.

6.-11  Volumetric flasks and graduated cylinders — Class A, borosilicate
glass or non-toxic plastic labware, 10-1000 nl, for culture work and
preparation of test solutions.

6.12  Volumetric pipets— Class A, 1-100 mL.


                                     59

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6.13   Serological  plpets—  1-10  mL,  graduated.

6.14   Pipet  bulbs  and fillers  ~ PropipetR,  8r  equivalent.

6.15   Disposable polyethylene  pipets,  droppers, and glass tubing with
fire-polished  edges,  2-mm ID —  for  transferring organisms.

6.16   Wash bottles — for rinsing small  glassware and  instrument
electrodes and probes.

6.17   Glass  or electronic thermometers —  for measuring  water temperatures.

6.18   Bulb-thermograph or electronic-chart type thermometers  ~  for
continuously recording temperature.

6.19   National Bureau of  Standards Certified thermometer — see  EPA  Method
170.1, USEPA 1979b.                                                      -

6.20   pH, .DO,  and  specific  conductivity meters  — for  routine physical  and
chemical measurements. Unless the test is being conducted to specifically
measure the  effect of one of the above parameters, a portable, field-grade
instrument is  acceptable.

6.21   Miscellaneous apparatus  and equipment  —  transfer  containers,  pumps,
and automatic  dilution devices should-be constructed of  materials as
indicated in Section  5, Facilities and Equipment.

7.    REAGENTS  AND  CONSUMABLE MATERIALS

7.1   Reagent water — defined  as activated-carbon-filtered distilled or
deionized water which does  not contain substances which  are toxic to the
test  organisms. A water  purification  system may be used to generate
reagent water  (see paragraph 6.5 above).

7.2   Effluent, surface water,  and dilution water — see  Section  7,
Dilution Water, and Section 8, Effluent and  Surface Water Sampling and
Sample Handling.   Dilution  water that  contains  undesirable organisms, that
may attack the test organisms  should be filtered through a fine  mesh net
(30-um or smaller  openings).

7.3   Reagents  for  hardness  and alkalinity  tests (see EPA Methods 130.2  and
310.1, USEPA 1979b).

7.4   pH buffers 4, 7, and 10 (or as  per instructions of  instrument
manufacturer)  for  standards and  calibration  check (see USEPA  Method  150.1,
USEPA 1979b).

.7.5   Membranes and filling  solutions for dissolved oxygen probe  (see USEPA
Method 360.1,  USEPA 1979b), or reagents  for  modified Winkler  analysis.

7.6   Laboratory quality assurance samples  and standards  for the  above
methods.

                                     60

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7.7  Specific conductivity standards  (see EPA Method  120.1, USEPA  1979b).

7.8  Reference toxicant solutions  (see Section 4, Quality Assurance).

7.9  Test Vessels — 30-mL borosilicate glass beakers or disposable
plastic salad dressing cups  (manufactured by Anchor-Hocking Plastic
Division, and supplied by Plastics Inc., 224 Ryan Avenue, St. Paul,
Minnesota, 55164) are recommended because they will fit in the viewing
field of most stereoscopic microscopes.  Rinse thoroughly in distilled
water and then in dilution water before use.  A volume of 15 ml of test
solution is adequate for the organisms, and will provide a depth in which
it is possible to count the animals with a minimum of re-focusing.  Ten
test vessels are used for each effluent dilution and for the control.

7.10  Test Organisms. — Neonate Ceriodaphnia dubia 2- to 24-h old and
released during the same 4-h period.See information on culturing methods
below,

7.10.1  The test organism (species being used) cultures should be started
at least two weeks before the brood animals are needed, to provide an
adequate supply of neonates for the test.  Only a few individuals are
needed to start a culture because of their prolific reproduction.

7.10.2  Ceriodaphnia may be shipped or otherwise transported in
polyethylene bottles.  Several hundred animals will live as long as one
week in a 1-L.bottle filled three-fourths full with culture medium
containing the trout chow diet (Paragraph 7.10.6.2.4 below).  Animals
received from an outside .source should be transferred to new culture media
gradually, over a period of 1-2 days, to avoid mass mortality.

7.10.3  It is best to start the culture from one animal, which is
sacrificed after producing young, embedded, and retained as a permanent
microscope slide mount.to facilitate identification and permit future
reference.  The species identification of the stock culture should be
verified by preparing slide mounts, regardless of the number of animals
used to start the culture.  The following procedure is recommended for
making slide mounts of Ceriodaphnia (Beckett and Lewis, 1982):

     1. Pipet the animal  onto a watch glass.
     2. Reduce the water volume by withdrawing excess water with the
        pipet.   -
     3. Add a few drops of carbonated water (club soda or seltzer
        water)or 701 ethanol to relax the specimen so that the
        post-abdomen is extended.  (Optional:   with practice,
        extension of the postabdomen may be accomplished by putting
        pressure on the cover slip.)
     4. Place a small  amount (one to three drops)  of mounting  medium
        on a glass microscope slide.  The recommended
                                  61

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         mounting medium is CMCP-9/9AF Medium^, prepared by
         mixing two parts of CMCP-9 with one part of CMCP-9AF.  For
         more viscosity and faster drying, CMC-10 stained with acid
         fuchsin may be used.
      5. Using a forceps or a pipet, transfer the animal to the
         drop of mounting medium on the microscope slide.
      6. Cover with a cover slip and exert minimum pressure to
         remove any air bubbles trapped under the cover slip.
         Slightly more pressure will extend the postabdomen.
      7. Allow mounting medium to dry.
      8. Make slide permanent by placing CMC-10 around the edges of
         the coverslip.
      9. Identify to species (see Pennak, 1978, and Berner, 1985).
     10. Label with waterproof ink or diamond pencil.
     11. Store for permanent record.

7.10.4  One-litre glass beakers are recommended for use as culture
vessels.  Use of aquaria (40- to 80-L, or 10- to 20-gal) and other types
of culture vessels may also be convenient.  Maintain cultures in several
(four or more) separate vessels to provide back-up cultures in case one is
lost due to accident or other problems, such as low DO concentrations or
lack of food.  Fill the 1-L culture vessels with 900 mL of medium.

7.10.5  A new culture is started each week, and the oldest culture is
discarded.  Using this schedule, 1-L .cultures will provide 500 to 1000
neonate Ceriodaphnia per week for use in the tests.

7.10.6  Feeding •                                               .

7.10.6.1  Feeding the proper amount of the right food is extremely
important in Ceriodaphnia culturing.  The key is to provide sufficient
nutrition to support normal reproduction without adding excess food which
may clog the animal's filtering apparatus or greatly decrease the DO
concentration, and lead to the death of the animals.  The suspension of
trout chow, yeast, and CEROPHYLR described below will provide adequate
nutrition if fed daily at the rate of 3 mL/L of medium.

7.10.6.2  The combined food  is prepared from three ingredients as follows:

7". 10.6.2.1  Digested trout chow:

    1. Add 5.0 g of No. 1 trout chow, U.S. Fish and Wildlife Service
       Specification Diet SD9-30, to  1 L of distilled or deionized
       water.  This trout chow may be obtained from Ziegler Bros.,
       Inc., P. 0. Box 95, Gardners,  PA,  17324.  Mix well in a
       blender and aerate continuously  (digest) for one week at
       ambient laboratory temperature prior to use.
TCMCP-9 and 9AF are available from Polysciences, Inc., Paul Valley
Industrial Park, Warrington, PA,  18976.   (215-343-6484).
                                  62

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    2. At the end of digestion period, place the mixture In a
       refrigerator and allow to settle overnight.  Decant 300 ml of
       the supernatant and combine with equal volumes of supernatant
       from CEROPHYLR and yeast preparations (below).  Discard the
       remainder.

7.10.6.2.2- Yeast:

    1. Add 5.0 g of dry yeast, such as FLEISCHMANN'SR or ST.
       REGISR, to 1 L of distilled water.
    2. Stir with a magnetic stirrer until well dispersed or use a
       blender at low speed for 5 min.
    3. Place in a refrigerator overnite, mix well, and combine
       300 mL with equal volumes of supernatant from the trout chow
       (above) and CEROPHYLR preparations (below).  Discard the
       remainder.

7.10.6.2.3  CEROPHYLR (Powdered, Dried," Cereal Leaves) 1:

    1. Place 5.0 g of CEROPHYLR powder in a blender.
    2. Add 1 L of distilled water.
    3. Mix at high speed for 5 min.
    4. Place in a refrigerator overnite to settle, decant 300 mL of
       the supernatant and combine with equal volumes of supernatant
       from trout chow and yeast preparations (above).  Discard the
       remainder.

7.10.6.2.4  Combined trout chow-yeast-CEROPHYLR food:

    1. Mix equal (300 mL) volumes of the three foods.
    2. Place aliquots of the final mixture in small (50 mL to
       100 mL) screw-cap plastic bottles and freeze until needed.
    3. Fresh or thawed food is stored in the refrigerator between
       feedings, and is used for a maximum of one week.

7.10.6.2.5  The quality of each batch of .food prepared with a new
supply of components should be determined by using the food in a
7-day reproduction test with control water (use culture medium, see
7.10.7, below).

7.10.7  Synthetic, moderately hard water (hardness of 80 to 100 mg/L as
CaCOs) is recommended as a standard culture medium (see Table 1, Section
7, Dilution Water).  Other culture water, such as well water, pond water,
or dechlorinated tap water, also may be satisfactory.
1 Available from Sigma Chemical Company, P.O. Box 14508, St. Louis,
Missouri, 63178. (800-325-3010).
                                     63

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7.10.8  Ceriodaphnia should be  cultured  at  a  temperature of 25 +  2°C   No
water temperature control equipment  is needed if the  ambient  laboratory
temperature remains in the recommended range,  and  if  there are no
frequent, rapid, large, temperature  excursions in  the culture room.

7.10.9  Day/night cycles prevailing  in most laboratories will provide
adequate illumination for normal growth  and reproduction.  A  16-h/8-h
day/night cycle is recommended.

7.10.10  Ceriodaphnia cannot survive DO  concentrations below  5 mg/L for
extended periods.However, aeration is  generally  not needed  unless the
cultures are overfed.  DO should be  measured  when  the cultures are first
started and weekly thereafter.  Aerate if the DO concentration drops below
5 mg/L.

7.10.11  Suspend a clear glass  or plastic panel over  the cultures to
exclude dust and dirt.  There should be  space for  circulation of  air over
the vessels to provide oxygen_for the cultures.

7.10.12  Ceriodaphnia are eaten by many  species of copepods and shrimp,
and cultures must be maintained free of  preditors.  Natural waters used as
culture media should be filtered through a  plankton net with  30 urn mesh
openings.                           .
7.10.13  Ceriodaphnia have been reported to be very sensitive to sudden pH
and temperature changes, and care should be taken to limit rapid changes
in pH to less than 0.5 units and rapid changes in water temperature to
less than 5°C.

7.10.14  The test organisms should be handled carefully and as little as
possible so that they are not unnecessarily stressed.  They should be
transferred from cultures to test vessels, and between test vessels, with
a pipet of approximately 2-mm bore, taking care to release the animals
under the surface of the water.  Any organism that is injured during
handling should be discarded.

7.10.15  Culture Maintenance

7.10.15.1  Cultures should be fed daily to maintain the organisms in  ,
optimum condition so as to 'provide maximum reproduction in the toxicity
tests.  Stock cultures which are stressed because they are not adequately
fed may produce large number of males and ephippial females.  Also, brood
females and their offspring may produce few young when used in the test.

    1. If food is frozen, remove a bottle of food from the freezer. 1 h
       before feeding time, and allow to thaw.
    2. Shake thoroughly.
    3-. Feed daily at the rate of 4 mL/L of medium.
    4. Return unused food mixture to the refrigerator.   Do not re-freeze.
       Discard unused portion after one week.
                                     64

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7.10.15.2  Careful  culture  maintenance is  essential.  The  population
should not be allowed  to  exceed  1000  animals/L  of medium.   If
necessary, thin  the cultures  every four or five days  after changing
the medium to prevent  crashes and  discourage  gametogenesis.

7.10.15.3  The culture medium in each culture vessel  should be
replaced with fresh medium  weekly  as  follows:

    1. Pour about one  half  (450 mL of the  900 mL) of  the contents of
       a culture vessel into  a shallow vessel.   A large finger bowl
       works well.
    2. Discard the  remainder  of the medium and  animals unless needed
       for a test or to start a new culture.
    3. Clean the culture  vessel by brushing the sides and  bottom, or
       wiping with  a clean  sponge  or  paper towel, and rinsing with
       distilled or deionized water.   Each month, the culture
      . vessels should  be  washed as  described  in  Section 5,
       (Facilities  and Equipment),  and  air dried.
    4. Place about  100 ml of  fresh  medium  in  the clean culture
       vessel.
    5. Remove about 100 Ceriodaphnia  from  the holding vessel (finger
       bowl) with a pipet,  plastic  tubing, or by dipping with a
       small beaker, and  transfer  them to  the fresh medium, along
       with a small amount  of  the  old.medium to  provide seed
       bacteria  for the new culture.
    6. Carefully add sufficient additional fresh medium to fill the
       culture vessel.

8.  SAMPLE COLLECTION, PRESERVATION AND HANDLING

8.1  See Section 8, Effluent  and Receiving Water Sampling and Sample
Handling.

9.  CALIBRATION AND STANDARDIZATION

9.1  See Section 4, Quality Assurance.

10.  QUALITY CONTROL

10.1  See Section 4, Quality Assurance.

11. PROCEDURE

11.1  TEST SOLUTIONS

11.1.1  Surface Waters

11.1.1.1   Surface water toxicity is determined with  samples used  directly
as collected.
                                     65

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11.1.2  Effluents

11.1.2.1  Thft selection of the effluent test concentrations should be
based on the objectives of the study.  One of two dilution factors,
approximately 0.3 or 0.5, is commonly used.  A dilution factor of
approximately 0.3 allows testing between 100% and 1% effluent using only
five effluent concentrations (100%, 30%, 10%, 3%, and 1%).  This series of
dilutions minimizes the level of effort, but because of the wide interval
between test concentrations provides poor test precision (+ 300%).
A dilution factor of 0.5 provides greater precision (+ 100%*), but requires
several additional dilutions to span the same range oF effluent
concentrations.  Improvements in precision decline rapidly as the dilution
factor is increased beyond 0.5

11.1.2.2  If the effluent is known or suspected to be highly toxic, a
lower range of effluent concentrations should be used (such as 10%, 3%,
1%, 0.3%, and 0.1%).  If a high rate of mortality is observed during the
first"1 to 2 h of the test, additional"dilutions at the lower range of
effluent concentrations can be added.

11.1.2.3  The volume of effluent required for daily renewal of 10
replicates per concentration, each containing'15 ml of test solution, is
approximately 1 I.  Prepare enough test solution (approximately 600 mL) at
each effluent concentration to provide 400 mL additional volume for
chemical analyses.

11.2   OBTAINING NEONATES FOR THE TEST

11.2.1  This test method requires neonates 2- to 24-h old (all within 4 h
of the same age) to begin the test. To obtain a sufficient number of young
which are all less than 4-h old, brood animals containing eggs are placed
singly in 30-mL beakers containing 15 mL of media (using the same source
of dilution water that will be used in the test), four or five days prior
to the initiation of the test.  One brood animal is needed for each test
vessel that will be used in the test.  For example, if five concentrations
and a control will be used in a test to begin on a Friday, 60 brood
animals are placed in individual beakers on Monday and fed daily, as in
the test (see Paragraph 11.6).  The brood stock are transferred to fresh
media daily, and the young are discarded with the old media.  Four hours
before the test is to begin, the young are removed from the brood beakers
and discarded.  In this way, all the young in the brood beakers when the
test is ready to start will be less than 4-h old, and are used in the
test.  Some workers prefer to begin removing and saving young from the
brood chambers at 2- or 4-h intervals beginning 8 h before the test is-
scheduled to start.  This makes it possible to use older, but similar
aged, young for beginning the test, thus improving chances of good
survival of test animals.
                                     66

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 11.3  START OF THE TEST

 11.3.1  The test should begin as soon as possible, preferably within 24 h
 of sample collection.  In no case should tn"e test be started more than 72
 h after sample collection.  Just prior to testing, the temperature of the
 sample should be adjusted to 25 + 1°C and maintained at that temperature
 until portions are added to the dilution water.

 11.3.2  Begin the test by randomly placing one neonate in each test
 beaker.  Because of their small size and difficulty in handling, the test
 chambers are usually placed in racks, 10 to a rack.  The position of the
 test chambers is randomized in the racks at the beginning of the test.  On
 following days, the positions of the racks are randomized.

 11.4  LIGHT, PHOTOPERIOD AND TEMPERATURE

 11.4.1  The light quality and intensity should be at ambient laboratory
 levels, approximately 10-20 u£/m2/s,  or 50 to 100 foot candles (ft-c),
 with a photoperiod of 16 h of light and 8 h of darkness.   It is critical
 that the test water temperature be maintained at 25 + 1°C to obtain
 three broods in seven days.                         ~"

 11.5  DISSOLVED OXYGEN             .

 11.5.1   Low DO concentrations may be  important when running  effluent
 toxicity tests.   However,  aeration is not practical  for the  Ceriodaphnia
 test.   If the DO in the effluent and/or dilution water is low,  aerate	
 before preparing the test  solutions.
                   f

 11.6  FEEDING

 11.6..1   During the  test, the  Ceriodaphnia are fed the  same diet  as  used
 for  the cultures.   The organisms  in the  test  vessels  are  fed digested
 trout  chow-yeast-CEROPHYLR diet  daily at a  rate of 0.1  mL  food
 suspension/15  mL  of test solution.

 11.7  TEST  SOLUTION RENEWAL

 11.7.1   Using  a  glass  or polyethylene  dropper,  or  pipet, transfer each
 test organism daily to a new  test vessel  containing 15 mL  of
freshly-prepared test  solution and 0.1 mL of  the food suspension.  The
 animals  should be released under the  surface  of the water  so that air is
 not trapped under the  carapace.

 11.8  ROUTINE, CHEMICAL AND PHYSICAL DETERMINATIONS

 11.8.1  At a minimum,  the following measurements are made:

 11.8.1.1  DO is measured in each test solution at the beginning of each
24-h exposure period,  and at the end of the exposure period in one test
vessel at each test concentrations and in the control, after the adult


                                     67                              '

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 has been removed and the young have been counted.  (Acid must not be added
 to count the young in that chamber.)

 11.8.1.2  Temperature, pH, and conductivity are measured at the beginning
 of each 24-h exposure period at all test concentrations and in the control.

 11.8.1.3  Alkalinity and hardness are measured at the beginning of each
 24-h exposure period in 100X effluent and in the control.

 11.9  OBSERVATIONS DURING THE TEST

 11.9.1  Three broods are usually obtained in the controls in  a seven-day
 test conducted at 25°C.  The first brood of two to five young is usually
 released on  the third day of the test, soon after the adults  are
 transferred  to fresh test solutions.  Successive broods are released every
 36 to 48 h thereafter, and may contain 10 to 15 young.

 11.9.2  Each day, at the time the organisms are to be transferred to fresh
 test solutions,  determine adult survival  and count and record the number
 of young.  First remove the adult to the new test solution.   Count any
 dead young,  and  then add two drops of IN hydrochloric acid  to the vessel
 (except the  vessel  used for DO measurements).   The living young die
 quickly and  settle  to the bottom of the test vessel where they may be
 counted with a minimum of effort and error.   The young  are  discarded after
 counting.

 11.9.3  The  young are best counted with the aid of a  stereomicroscope.
 The organisms  are more easily seen if viewed against  a  black  background.
 If counts  are  made  without the aid of a stereomicroscope, place the test
 vessels on a black  strip of tape on a light  box.

 11.9.4  In the absence of toxic  substances,  young  production  may exceed 30
 per adult.   If toxic  substances  are present, young may  develop  in  the
 brood  pouch  of the  adults,  but may not  be released during the exposure
 period.

 11.10   TERMINATION  OF  THE TEST

 11.10.1  Because  of the  rapid  rate of development  of Ceriodaphm'a, the
 test must be terminated  and  all  observations completed within + 2 h of
 exactly seven  days"  after the initiation of the  test.  The seveF-day test
 period was selected because  each control animal will normally produce
 three broods,  totaling 10 to 30, at a test temperature of 25°C.  An
 extension of more than a few hours  in the test  period would be a
 significant part of the  brood  production cycle  of the animals, and could
result  in additional broods.

 11.11  SUMMARY OF TEST CONDITONS

 11.11.1  A summary of test conditions is listed in Table 1.
                                     68

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12. CALCULATIONS   .

12.1  DATA PREPARATION                       ,  ?

12.1.1  The number of young produced per adult female Is determined by
taking the total number of young produced until either the time of death
of the adult or the end of the experiment, whichever comes first.   An
animal that dies before producing young would be included in the analysis,
with zero entered as the number of young produced.  The subsequent
calculation of the mean number of young produced per adult for each
toxicant concentration provides a combined measure of the toxicant's
effect on both mortality and reproduction.

12.1.2  Tabulate and summarize the data.  A sample set of test data are
listed in Table 2.  Using these data, the total number of young produced
per adult during the test is shown in Table 3.

12.2. DATA ANALYSIS

12.2.1  Fisher's Exact Test (Finney, 1948; Pearson and Hartley, 1962) and
Dunnett's Procedure (Dunnett, 1955) or Steel's Many-One Rank Test (Steel,
1959; Miller, 1981) are used to analyze the data.  The first step.is to
test for a significant difference in the survival of the original test
organisms in the various effluent concentrations and control, using
Fisher's Exact Test.  Dunnett's Procedure is then used to analyze the
reproduction data from only those effluent concentrations where mortality
was not significantly different from the controls.
                    i»
12.2.2  For the data in Table 3, reference to the tabulated values in
Appendix E show that the survival in 25% effluent is significantly
different from the control survival.  Therefore, the 25% effluent
concentration will not be included in the analysis of the reproduction
data.

12.2.3  Since it is border-line as to whether the remaining data meet the
assumptions for normality, both Dunnett's Procedure and Steel's Many-One
Rank Test can be used to analyze the reproduction data.

12.2.4  The safe concentration derived from the test is reported as the
NOEC.            •

12.2.5  Dunnett's Procedure
            •'ty>& <•-  • '
12.2.5.1  Dunnett's procedure includes an analysis of variance (ANOVA)
followed by a comparison of each toxicant concentration mean with the
control mean.  The error value calculated in the ANOVA is used in the
comparison of the control and treatment means.  An example of a Dunnett's
calculation is included in the Appendix.  The computer program listed in
the Appendix generates output which includes an ANOVA table, a statement
about each treatment mean that can be used to identify the NOEC,  and the
minimum difference between treatment and control  means that can be
detected as statistically significant.

                                     69

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 12.2:5.2  The analysis is carried out using the total number of live young
 produced by each adult female during the the test (Table 3).

 12.2.5.3  The output from the analysis of variance is shown in Table 4,
 and indicates that the effects of the various treatments on reproduction
 were significant at P * 0.05.

 12.2.5.4  The computer output for the comparison of the control  mean with
 the treatment means is shown below:

     THERE IS NO SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 2
     (IX EFFLUENT)  AND CONTROL.

     THERE IS NO SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 3
     (3X EFFLUENT)  AND CONTROL.

     THERE IS NO SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 4
     (6X EFFLUENT)  AND CONTROL. ,        '        •     .

     THERE IS NO SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 5
     (12X EFFLUENT)  AND CONTROL.

 12.2.5.5  The NOEC and LOEC,  as determined  from the  analysis,  were
 12% and 25%  effluent,  respectively.   Note that the Dunnett  program
 considers the control  as Concentration 1.   Thus, Concentration 5 in
 the output from Dunnett's test is  effluent  Concentration 4
 (12% effluent)  in  the test.

 12.2.5.6  For this  set of data, the minimum difference that  can be
 detected as  statistically significant  is 6.28 young  per adult.  This
 represents a 34.5%  reduction  in the response from the control.

 12.2.6   Steel's  Many-One Rank  Test

 12.2.6.1  Steel's Many-One Rank Test compares several treatments
with a control  by analyzing the ranks  of the data, thereby
 eliminating  the  necessity that the data meet the normality
 assumptions.  The calculations for Steel's Many-One Rank Test of the
data in Table 3 are detailed  in the Appendix.  The NOEC determined
from Steel's Test was  12X, which agrees-with the NOEC from Dunnett's
Procedure above.

12.2.7 The chronic value (ChV) is the geometric mean of the NOEC and
LOEC and is calculated as follows:

    Log.io NOEC  »  Logic 12  *  1.0792
    Logic LOEC  =  Logic 25  *  1.3979
    ChV  *  Antilog (1.0792 + 1.3979)/2  -•  Antilog 1.2386
    ChV  »  17.3% effluent
                                  70

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13.  PRECISION AND ACCURACY
13.1  PRECISION v
13.1.1  Infonnatldh on the single laboratory precision of the
Ceriodaphnia reproduction test based on the NOEC and LOEC values
from nine tests with the reference toxicant NaPCP is provided in
Table 5.
13.2  ACCURACY
13.2.1  The accuracy of toxicity tests cannot be determined.
                                  71

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      TABLE U  SUMMARY OF RECOMMENDED TEST CONDITIONS FOR CERIODAPHNIA
                SURVIVAL AND REPRODUCTION TEST             	
 1. Test type:
 2. Temperature (°C):
 3. Light quality:
 4. Light intensity:

 5. Photoperiod:
 6. Test vessel size:
                      m  •     '
 7. Test solution volume:
 8. Renewal of test concentrations:
 9. Age of test organisms:     -   -
10. Number of test organisms
     per chamber:
11. Number of replicate
     chambers per treatment:
12. Feeding regime:
13. Aeration:
14. Dilution water:

15. Dilution factor:
16. Test duration:
17. Effects measured:
 Static  renewal
 25 i 1°C
 Ambient laboratory  light
 10-20 uE/m2/s, or 50-100 ft-c
 (ambient  laboratory levels)
 16 h  light, 8 h dark
.30 mL
 15 mL
 Daily
 Less  than 24 h; and all released
 within  a 4-h period
 1
10
Feed 0.1 mL food suspension/15 mL,
daily
None
Moderately hard standard water,
receiving water, other surface
water, or ground water with hardness
similar to receiving water
Approximately 0.3 or 0.5
7 days
Survival and reproduction
                                   72

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             TABLE 2.  DATA FROM CERIODAPHNIA EFFLUENT TOXICITY TEST
Effl   Day
Replicate
Total   No.    Most Young
Live   Live    By Any
Cone..
Cont
1.0%
3.0%
6.0%
12.0%
25.0%
No.
3
4
5
6
7
3
4
5
6
7
3
4
5
6
7
3
4
5
6 .
7
3
4
5
6
7
3
4
5
6
• 7
. A
0
2
9
5
6
TZ
0
2
9
6
27
0
2
3
10 .
10
TS
0
2
2
9
10
2T
0
0
1
8
11
m
0
X
-ff
8
0
2
2
6
8
Tff
0
4
5
3
TT
0
i
4
8
12
2T
0
4
3
2
2
Tff
0
4
8
4
2T
0
0
X
IT
c
0
4
9
9
5
IT
0
i
2
6
12
FT
0
2
2
6
»
0
2
0
2
3
0
2
0
8
if
0
0
1*
T
0
0
0
0
6
10
Tff
0
0
.0
2
4
T
0
4
9
9
2
IT
0
2
2
3
6
TT
0
2
2
3
6
TT
0
0
X
"o1
E
0
6
9
0
1
TC
0
4
8
3
3
27
0
4
n
•o
0
17
0
0
4
10
12
is
0
2
3
10
10
I?
0
X
IT
F
X
~s
0
2
.13
8
8
3T
0
8
6
3
6
IT
0
1
2
6
13
IF
0
0
3
10
12
•"25*
0
X
~Q
G
0
2
0
3
"1
0
2
2
10
9
IT
•o
Z
2
6
n
FT
0
2
2
8
9
IT
0
1
0
5
10
TF
0
0
X
"o1
H
0
6
6
5
8
TS
0
3
" 8
0
0
TT
0
0
4
10
8
IF
0
0
4
6
11
IT
d
2
2
10
n
•US
0
X
-^
I
0
1
2
11
10
2T
0
2
2
6
13
If
0
4
8
8
0
Iff
0
4
6
2
9
IT
0
1
3
6
8
Iff
0
0
X
IT
J
0
4
9
10
if
0
2
2
6
12
2?
0
3
6
3
6
TS
3
2
8
4
4
IT
0
4
0
7
7
Tff
0
0
X
IT
Young
0
27
46
55
54
187
0
22
51
55
69
197
0
30
55
63
65
2TJ
3
19
38
52
79
19T
0
18
22
71
87
13S
0
0
1
0
0
Adults
9
9
9
9
9
10
10
10
10
10
10
10
10
10
10.
10
10
10
10
10
10
10
10
10
10
10
6
1
0
0
One Adult
0
6
9
11
10
0
4-
13
10
13
0
8
11
10
12
3
4
8
10
13
0
4
3
10
12
0
0
1
0
0
x 3 dead adult, no young produced before death.
1X s Dead adult; one young produced before death.
Note: Days 1 and 2 are not included because young were not produced until
       the third day.  Adult mortality was not recorded for days 1  and 2.
                                       73

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           TABLE 3.   NUMBER OF YOUNG PRODUCED PER CERIQDAPHNIA
                               Effluent Concentration (%)
Replicate
(Organism)
A
B
C
0
E
F
G
H
I
J
Control
22
18
27
16
16
0
a
25
24
26
1
22
15
21
6
23
31
23 ,
11.
23
22
3
25
25
20
24
15
23
21
22
20
18 .
6
23
16
7
13
26
22
21
21
21
21
12
20
21
17
13
25
25
16
25
18
18
25
0
0
1
0
0
0
0
0
0
0
   TABLE 4.  ANALYSIS OF VARIANCE OF CERIODAPHNIA REPRODUCTION DATA
             FROM CONTROL AND FIRST FOUR. EFFLUENT CONCENTRATIONS (1-12*)

                                                 Calculated  Tabular
 Source     DF     Sum of Squares   Mean Square      F        FQ.QS
Among
Within
4
- 45 '
51.480
1664.300
12.870
36.984
0.35 2.58
TOTAL
49
1715.780
                                   74

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 TABLE 5.  PRECISION OF THE CERIODAPHNIA REPRODUCTION TEST,
           USINfrNAPCP AS A REFERENCE TOXICANT*
Test -
lb
2C
3
4d
5
6
7
8
• 9
NOEC
(mg/L)
0.25
0.20
0.20
0.30
0.30
0.30
0.30
0.30
0.30
LOEC
(mq/L)
0.50
0.60
0.60
0.60
0.60
0.60
0.60
0.60
- 0.60
Chronic
Value
(mg/L)
0.35
0.35
0.35
0.42
0.42
0.42
0.42
0.42
0.42
aFor a discussion of the precision of data from chronic toxicity
 tests see Section 4, Quality Assurance.
bConcentrations used in Test 1 were;  0.03, 0.06, 0.12,  0.25, 0.50,
 1.0 mg NaPCP/L.
concentrations used in Tests 2 and  3 were,  0.007,  0:022, 0.067,
 0.20, 0.60 mg NaPCP/L.
dConcentrations used in Tests 4 through 9 were, 0.0375, 0.075,
 0.150, 0.30, 0.6Q mg NaPCP/L.
                                  75

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                                 SECTION  14-

                               TEST  METHOD!.2

                ALGAL (SELENASTRUM CAPRICORNUTUM) GROWTH TEST
                                METHOD 1003.0

1.  SCOPE AND APPLICATION

1.1  This method measures the chronic toxicity of whole effluents and
receiving water to the fresh water alga, Selenastrum capricornutum, during
a four-day, static exposure.  The effects  include the synergistic,
antagonistic, and additive effects of all  the chemical, physical, and
biological components which adversely affect the physiological and
biochemical functions of the test organisms.

1.2  Detection limits of the toxicity of an effluent or pure substance are
organism dependent.

1.3  Single or multiple excursions in acute toxicity may not be detected
using 24-h composite samples.  Also, because of the long sample collection
period involved in composite sampling, and because the test chambers are
not sealed, highly volatile and  highly degradeable toxicants in the source
may not be detected in the test.

1.4  This-test is very versatile because it can also be used to identify
wastewaters which* are biostimulatory and may cause nuisance growths of
algae, aquatic weeds, and other  organisms  at higher trophic levels.

1.5  This method is restricted to use by or under the supervision of
professionals experienced in aquatic toxicity testing.

2.  SUMMARY OF METHOD

2.1  A Selenastrum population is exposed in a static system to a series of
concentrations~~of" effluent, or to receiving water, for 96 h.  The response
of the population is measured in terms of changes in cell density (cell
counts per mL), biomass, chlorophyll content, or absorbance.  By extending
the test to 14 days, it may be used to measure the algal growth potential
of wastewaters and surface waters.

3.  DEFINITIONS

    (Reserved for addition of terms at a later date.)
     format used for this method was taken from Kopp, 1983.
2This method was adapted from Miller et al, 1978.
                                     76

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4.  INTERFERENCES.
4.1  Toxic substances may be Introduced by contaminants in dilution
water, glassware, sample hardware, and testing equipment (see Section 5,
Facilities and Equipment).
4.2  Adverse effects of high concentrations of suspended and/or dissolved
solids, and extremes of pH, may mask the presence of toxic substances.
4.3  Improper effluent sampling and handling may adversely affect test
results (see Section 8, Effluent and Receiving Water Sampling and Sample
Handling).
4.4  Pathogenic and/or predatory organisms in the dilution water and
effluent may affect test organism survival, and confound test results.
4.5  The amount of natural nutrients in.the effluent or dilution water -
may confound test results.
5.  SAFETY
5.1  See Section 3, Safety and Health.
6. APPARATUS AND EQUIPMENT
6.1  Laboratory Selenastrum culture unit — See culturing methods below.
To test effluent toxicity, sufficient numbers of log-phase-growth
organisms must be available.
6.2  Samplers — Automatic sampler capable of collecting a 24-h composite
sample of 1 L.
6.3  Sample containers — for sample shipment and storage see Section 8,
Effluent and Receiving Water Sampling and Sample Handling.
6.4  Environmental chamber, incubator, or equivalent facility — with
cool-white fluorescence illumination (60 uE/m2/s, or 400 ^ 40 ft-c) and
temperature control (24 + 2°C).
6.5  Mechanical shaker — Capable of providing orbital motion at the rate
of 100 cycles per minute (cpm)
6.6  Light meter — with a range of  0-200 uE/m2/* (0-1000 ft-c).
6.7  Water purification system — Millipore Super-Q or equivalent;
6.8  Balance — Analytical, capable of accurately weighing 0.0001 g.
6.9  Reference weights, Class S — for checking performance of balance.
6.10  Glass or electronic thermometers — for measuring water
temperatures.
                                     77

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6.11,  Bulb-thermograph or electronic-chart type thermometers — for
continuously recording temperature.
6.12  National Bureau of Standards Certified thermometer (see EPA Method
170.1, USEPA 1979b).
6.13  Meters: pH and specific conductivity — for routine physical and
chemical measurements.  Unless the test is being conducted to
specifically measure the effect of one of the above parameters, a
portable, field-grade instrument is acceptable.
6.14  Fluorometer (Optional) — Equipped with chlorophyll detection light
source, filters, and photomultiplier tube (Turner Model 110 or
equivalent).
6.15  UV-VIS spectrophotometer — capable of accommodating 1-5 cm
cuvettes.
6.16  Cuvettes for spectrophotometer — 1-5 cm light path.
6.17  Electronic particle counter (Optional) —  Coulter Counter, ZBI, or
equivalent, with mean cell (particle) volume determination.
6.18  Microscope — with 10X, 45X, and 100X objective lenses, 10X ocular
lenses, mechanical stage, substage condenser, and light source (inverted
or conventional microscope).
6.19  Counting chamber — Sedgwick-Rafter, Palmer-Maioney, or
hemocytometer.
6.20  Centrifuge — with swing-out buckets having a capacity of 15-100 mL.
6.21  Centrifuge tubes,— 15-100mL, screw-cap.
6.22  Filtering apparatus — for membrane and/or glass fiber filters.
6.23  Volumetric flasks and graduated cylinders — Class A, 10-1000 ml,
borosilicate glass, for culture work and preparation of test solutions.
6.24  Volumetric pipets— Class A, 1-100 ml.
6.25  Serological pipets— 1-10 ml, graduated.
6.26  Pipet bulbs and fillers — PropipetR, or equivalent.
6.27  Wash bottles — for rinsing small glassware, instrument electrodes,
and probes.
6.28  Culture flasks — 1-4 L borosilicate, erlenmeyer flasks.
6.29  Test flasks — 125 or 250 ml borosilicate, erlenmeyer flasks.

                                     78

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 6.30  Preparation of glassware — prepare all  graduated cylinders, test
 flasks,  bottles-;  volumetric flasks,  centrifuge tubes and vials used in
 algal  bioassays  as follows:                •

 6.30.1  Wash with non-phosphate detergent solution,  preferably heated to
 50°C or  hotter.   Brush  the inside of flasks with a stiff-bristle brush
 to  loosen  any  attached  material.   The use of a commercial  laboratory
 glassware  washer  or heavy-duty kitchen dishwasher (under-counter type) is
 highly recommended.

 S.30.2  Rinse  thoroughly with  tap water,  and drain well.

 6.30.3  All  new test flasks, and  all  flasks which through  use may become
 contaminated with toxic organic substances, must be  rinsed with acetone
 or  heat-treated before  use. To thermally degrade organics, place
 glassware  in a high temperature oven  at 40QQC  for 30 min.   After
 cooling, proceed  with the next step.

 6.30.4  If acetone is used in  6.30.3,  rinse thoroughly  with tap water.
 If  the heat  treatment is  used,  go directly to  6.30.5.

 6.30.5  Carefully rinse with a 10% solution (by volume)  of reagent grade
 hydrochloric acid (HC1);  fill  vials and centrifuge tubes with the 10% HC1
 solution and allow to stand a  few minutes;  fill  all  larger containers  to
 about  one-tenth capacity  with  HC1  solution  and swirl  so that the entire
 surface  is bathed.

 6.30.6  Rijise with'tap  water and  drain  well.

 6.30.7  To neutralize any residual acid,  rinse with  a saturated solution -
 of
6.30.8  Rinse five times with tap water and then five times with
deionized or distilled water.

6.30.9  Dry in an oven, cover the mouth of each vessel with aluminum foil"
or other closure, as appropriate, before storing.

6.31  Use of sterile, disposable pipets will eliminate the need for pipet
washing and minimize the possibility of contaminating the cultures with
toxic substances.-

7. REAGENTS AND CONSUMABLE MATERIALS

7.1  Reagent water — defined as carbon-filtered distilled or deionized
water which does not contain substances which are toxic to the test
organisms.  A water purification system may be used to generate reagent
water (see paragraph 6.7 above).

7.2  Effluent, surface water, and dilution water — see Section 7,
Dilution Water, and Section 8, Effluent and Receiving Water Sampling and
Sample Handling.

                                     79       '.

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7.3  Reagents for hardness and alkalinity tests (see EPA Methods 130.2
and 310.1, USEPA 1979D).

7.4  pH buffers 4, 7, 8 and 10 (or as per instructions of instrument
manufacturer) for standards and calibration check (see USEPA Method
150.1, USEPA 1979b).

7.5  Laboratory quality assurance samples and standards for the above
methods.

7.6  Specific conductivity standards (see EPA Method 120.1, USEPA 1979b).

7.7  Reference toxicant solutions (see Section 4, Quality Assurance).

7.8  Acetone — pesticide quality or equivalent.

7.9  Dilute hydrochloric (or nitric) acid  — carefully add 10 mL of
concentrated HC1 to 90 'mL of reagent water.

7.10  Test Organisms — log-phase-growth Selenastrum capricornutum.  See
information on culturing methods below.

7.10.1  Culture Medium

7.10.1.1  The culture medium is used to maintain the stock cultures of
the test organisms, for the control flasks in each test, and as a.diluent
in tests to measure the toxicity of effluents and receiving waters.

7.10.1.2  Prepare five stock nutrient solutions using reagent grade
chemicals as described in Table 1.

7.10.1.3  Add 1 mL of each stock solution, in the order listed in
Table 1, to approximately 900 mL of distilled or deionized water.  Mix
well after the addition of each solution.  Dilute to 1 L, mix well, and
adjust the pH to 7.5 £0.1, using 0.1N sodium hydroxide or hydrochloric
acid, as appropriate.  The final concentration of macronutrients and
micronutrients in the culture medium is given in Table 2.

7.10.1.4  Immediately filter the pH-adjusted medium through a 0.45um pore
diameter membrane at a vacuum of not more than 380 mm (15 in.) mercury,
or at a pressure of not more than one-half atmosphere (8 psi).  Wash the
filter prior to use by passing 500 mL of distilled water through it.

7.10.1.5  If the filtration is carried out with sterile apparatus,
filtered medium can be placed immediately into sterile culture flasks,
and-no further sterilization steps are required before the inoculation of
the medium.  The medium can also be sterilized by autoclaving after it is
placed in the culture flasks.  However, the pH should be checked after
autoclaving to determine if it was changed.
                                     80

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    TABLE T. NUTRIENT STOCK SOLUTIONS FOR MAINTAINING ALGAL STOCK CULTURES
                          AND TEST CONTROL CULTURES.
Nutrient
Stock
Solution
   Compound
Amount dissolved in
500 mL Distilled Water
    £
    3_
    4_
    5
              FeCl3*6H26
              CoCl2'6H20
Na2EDTA'2H20
NaNOs
K2HP04
NaHC03
         6.08  g
         2.20  g
        92.8   mg
       208.0   mg
         1.64  rag*
        79.9   mg
         0.714 mgb
         3.63  mgc
         0.006 mgd
       150.0   mg
        12.750 g
         7.350 g
         0.522 g
         7.50  g
aZnCl2 - Weigh out 164 mg and dilute to 100 mL.  Add 1 mL of this
 solution to Stock II.
bCoCl2 '6H20 " Wel9h out 71.4 mg and dilute to 100 mL.  Add 1 mL of
 this solution to Stock #1.
               - Weigh out 36.6 mg and dilute to 10 mL.  Add 1 mL
 of this solution to Stock #1.
dCud2 -2H20 ,'•- Weigh out 60.0 mg and dilute to 1000 mL.  Take 1 mL
 of this solution and dilute to 10 mL.  Take 1 mL of the second dilution
 and add to Stock #1.
                                      81

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Table 2.  FINAL CONCENTRATION OF MACRONUTRIENTS AND MICRONUTRIENTS
          IN THE CULTURE MEDIUM
Macronutrient
NaN03
MgCl2-6H20
CaC12-2H20
MgS04.7H20
K2HP04
NaHC03'

-
Micronutrient
H3B03
MnCl2-4H20
ZnCl2
CoCl2-6H20
CuCl2*2H20
Na2Mo04«2H20
FeCl3.6H20
Na2EDTA*2H?b
Concentration
(mq/L)
25.5
12.2
4.41
14.7
1.04
: is.o .

.• -•
Concentration
(uq/L)
185
416 •
3.27
1.43
0.012
7.26
160
300
Element
N
Mg
Ca
S
P
Na
K
C
Element
B
Mn
Zn
Co
Cu
Mo
Fe
— —
Concentration
" (mg/L)
4.20
2.90
1.20
1.91
0.136
11.0
0.469
2.14
Concentration
(uq/L)
32.5
115
1.57
0.354
0.004
2.88
33.1
....
                                82

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7.10.1.6  Unused sterile medium should not be stored In the (250 ml) test
culture flasks more than one week prior to use, because there may be
substantial Toss of water by evaporation.

7.10.2  Algal Cultures

7.10.2.1  Test organisms —  Selenastrum capricornutum, a unicellular
coccoid green alga.  See Section 6, Test Organisms, for information on
sources of "starter" cultures.

7.10.2.2   Stock algal cultures

7.10.2.2.1 Upon receipt of the "starter" culture (usually about 10 ml), a
stock.culture is initiated by aseptically transferring 1 ml to a culture
flask containing control algal culture medium (prepared as described
above).  The volume of stock culture medium initially prepared will
depend upon the number of test flasks to be inoculated later from the  -
stock, or other planned uses,, and may range from 25 ml in a 125 ml flask
to 2 L i.n a 4-L flask. "The remainder of the starter culture can be held
in reserve for up to six months in a refrigerator (in the dark) at 4°C.

7.10.2.2.2  Maintain the stock cultures at 24 + 2°C, under continuous
"Cool-White" fluorescent lighting of 86 + 8.6 u£/m2/s, or 400 + 40
ft-c.  Shake continuously at 100 cpm or once daily by hand.   "~

7.10.2.2.3  Transfer 1 to 2 mL of stock culture weekly to 1 L of new
culture medium to maintain a continuous supply of "healthy" cells for
tests.  Aseptic techniques should be used in maintaining the algal
cultures, and extreme care should be exercised to avoid contamination.

7.10.2.2.4  To maintain unialgal culture material over a long period of
time, it is advantageous to use a semi-solid medium containing 1.0%
agar.  The medium is placed in sterile Petri dishes, and a 1-mL portion
of a liquid algal culture is streaked onto it and incubated as described
above.  Place rubber bands around the petri dishes to reduce evaporation
loss of the medium.  Fresh (liquid) stock cultures may be started at four
week intervals by transfer of cells from a single clone in a petri dish
to an appropriate volume of liquid medium.

8.  SAMPLE COLLECTION, PRESERVATION AND HANDLING

8.1  See Section 8, Effluent and Receiving Water Sampling and Sample
Handling.

9.  CALIBRATION ANO STANDARDIZATION

9.1  See Section 4, Quality Assurance.

10.  QUALITY CONTROL

10.1  See Section 4, Quality Assurance.


                                    83

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11.  PROCEDURES

11.1  TEST SOLUTIONS

11.1.1  Surface Waters

11.1.1.1  Surface water toxicity is determined with samples used directly
as collected.

11.1.2  Effluents

11.1.2.1  The selection of the effluent test concentrations should be
based on the objectives of the study.  One of two dilution factors,
approximately 0.3 or 0.5, is commonly used.  A dilution factor of
approximately 0.3 allows testing between 100% and 1% effluent using only
five effluent concentrations (100%, 30*, 10%, 3%, and 1%).  This series
of dilutions minimizes the level of effort, but because of the wide
Interval between test concentrations provides poor test precision
(j^300S).  A dilution factor" of 0.5 provides greater precision (£ 100X),
but requires several additional dilutions to span the same rangeTof
effluent concentrations.  Improvements in precision decline rapidly as
the dilution factor is increased beyond 0.5

11.1.2.2  If the effluent is known or.suspected to be highly toxic, a
lower range of effluent concentrations should be used (such as 1051, 3%,
1%, 0.3S, and 0.1%).  If a high rate of mortality is observed during the
first 1 to 2 h of the test, additional dilutions at the lower range of
effluent concentrations can be added.

11.1.2.3  The volume of effluent required for the test is 1 L.  Prepare
enough test solution at each effluent concentration (approximately 700
mL) to provide 100 mL of test solution for each of three replicate test
chambers and 400 mL for chemical analyses.

11.1.3  Dilution water may consist of stock culture medium without the
EDTA, or other water such as surface water, depending on the objectives
of the test.  However,-if water other than the stock culture medium is
used for dilution water, -1 mL of each stock nutrient solution (except for
EDTA) should be added per litre of dilution water.  Surface waters used
as dilution water must be filtered through a 0.45 urn pore diameter
filter, such as a-GF/A, GF/C, or equivalent filter.

11.1.4  Effluents may be toxic and/or nutrient poor.  "Poor" growth in an
algal toxicity test, therefore, may be due to toxicity or nutrient
limitation, or both.  To eliminate false negative results due to low
nutrient concentrations, 1 mL of each stock nutrient solution (except
EDTA) is added per litre of effluent prior to use in preparing the test
dilutions.  Thus, all test treatments and controls will contain at least
the basic amount -of nutrients.

11.1.5  If the growth of the algae in the test solutions is to be
measured with an electronic particle counter", the effluent and dilution

                                    84

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water must brfiltered through a GF/A, GF/C, or equivalent pore diameter
filter, and checked for "background" particle count before it is used in
the test.

11.1.6  If samples contain volatile substances, the test sample should be
added below the surface of the dilution water towards the bottom of the
test container through an appropriate delivery tube.

11.2  PREPARATION OF INOCULUM

11.2.1  The inoculum is prepared no more than 2 to 3 h prior to the
beginning of the test, using Selenastrum capricornutum harvested from a
four- to seven-day stock culture!  Each mi Hi liter of inoculum must
contain enough cells to provide an initial cell density of 10,000
cells/ml in the test flasks.  Assuming the use of 250 mL flasks, each
containing 100 mL of test solution, the inoculum must contain 1,000,000
cells/mL.  Estimate the.volume of stock, culture required to prepare the
inoculum as described  in the following example:


    If the seven- to 10-day stock culture used as the source of the
    inoculum has a cell density of 2,000,000 cells/mL, a test
    employing 25 flasks, each containing 100 mL of test medium and
    inoculated with a  total of 1,000,900 cells, would require
    25,000,000 cells or 12.5 mL of stock solution
    (25,000,000/2,000,000) to provide sufficient inoculum.  It is
    advisable to use a volume 20 to 50% i-n excess of the minimum-
    volume required, to cover accidental loss  in transfer and
    handling.

    1. Determine the density of cells (cells/ml) in the stock
       culture (for this example, assume 2,000,000 per mL).
    2. Calculate the required volume  of stock  culture as follows:

Volume  (mL) of      Number of flasks  X Volume  of Test X 10,000 cells/mL
Stock Culture  s      to be used	Solution/Flask	
Required             Cell density (cells/mL) in the stock culture

                =       25 flasks X  100 nt/flask X  10.000 cells/Hi
                 .  ''             2,000,000  cells/mL

                «    12.5 mL Stock Culture

    3.  Centrifuge  20 mL of  stock culture  at 1000 x g for 5 rain.
       This volume will provide  a 50% excess in the number of cells.
    4.  Decant the  supernatant  and resuspend the eel Is-in 15 mL of
        distilled or deionized water.
    5.  Repeat the  centrifugation  and decantation step,  and resuspend
        the cells  in 15 mL  distilled or  deionized water.
    6.  Mix well  and determine  the  cell  density in  the makeup water.
        Some cells  will be  lost  in  the concentration process.
                                   85

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       Dilute the cell concentrate as needed to obtain a cell density of
       1,000,000 cells/ml, and check the cell density In the final Inoculum.

11.3  START OF THE TEST

11.3.1  Tests should begin as soon as possible, preferably within 24 h of
sample collection.  If the persistence of the sample toxicity 1s not
known, the maximum holding time should not exceed 36 h.  In no case should
the test be started more than 72 h after sample collection.  Just prior to
testing, the temperature of the sample should be adjusted to that of the
test (24 +• 2°C) and maintained at that temperature until portions are
added to the dilution water.

11.3.2  The test begins when the algae are added to the test flasks.

    1. Mix the inoculum well, and add 1 ml to the test solution in each
      . flask.
    2. Make a final check of the cell density in three of the test
      ,solutions at time "zero * (within 2 h of the inoculation).

11.4  LIGHT, PHOTOPERIOO, AND TEMPERATURE

11.4.1  Test flasks are incubated- under continuous illumination at
86 + 8.6 uE/m2/s (400 + 40 ft-c), at 24 > 2°C, and should be shaken
coritinously at 100 cpoTon a mechanical shaker or twice daily by hand.
Flask positions in the incubator should be randomly rotated each day to
minimize possible spatial differences in illumination and temperature on
growth rate.  If it can be verified that test specification are met at all
positions, this need not be done.

11.5  ROUTINE CHEMICAL AND PHYSICAL DETERMINATIONS

11.5.1  Measure the pH.and specific conductivity of the highest, midrange,
and lowest effluent concentrations and the dilution water when the test
dilutions are prepared.  Additional measurements may be appropriate
depending on the test objectives.

11.6  OBSERVATIONS DURING THE TEST

11.6.1  Toxic substances in the test solutions may degrade or volatilize
rapidly, and the inhibition in algal growth may be detectable only during
the first one to two days in the test.  It may be desirable, therefore, to
determine the algal growth response daily.

11.7  TERMINATION OF THE TEST

11.7.1  The test is terminated 96 h after initiation.   The algal growth in
each flask is measured by one of the following methods:   (a) cell counts,
(b) chlorophyll content, or (3) turbidity (light absorbance).  Regardless
of the method used to monitor growth, the algae in the test solutions
should be checked under the microscope to detect abnormalities in cell
size or shape.

                                     86

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  11.7.2  Cell Counts

  11.7.2.1  Automatic Particle Counters

  11.7.2.T.1  Several types of automatic electronic and optical particle
  counters are available for use in the rapid determination of cell density
  (cells/mD-and mean cell volume (MCV) in um3/cell.  The Coulter Counter is
  widely used and is discussed in detail by Miller et al., 1978.

  11.7.2.1.2  If biomass data are desired for algal growth potential
 measurements, a Model ZBI or ZB Coulter Counter is used.  However, the
  instrument must be calibrated with a reference sample of cells of known volume.

  11.7.2.1.3  When the Coulter Counter is used, an aliquot (usually 1 mL) of the
 test culture is suspended in a 1% sodium chloride electrolyte (such as
 IsotonK), in a ratio of 1 mL of test culture to 9 ml (or 19 mL)  of 0.22-ura
 filtered saline solution (dilution of 10:1 or 20:1). The resulting dilution is
 counted using an aperture tube with a 100-urn diameter aperature.  Each cell
 (particle)  passing through the aperture causes a voltage drop proportional  to
 its volume.  Depending on the model, the instrument stores the information  on
 the number  of particles and the volume of each, and calculates the mean cell
 volume.

 The following procedure is used:      -

     1.  Mix  the algal  culture in the flask thoroughly by swirling the contents
        of the flask  approximately  six times  in a clockwise direction,  and then
        six  times in  the-reverse directionj repeat the two-step process at
        least once.
     2. At the end  of  the  mixing process,  stop  the motion  of  the  liquid in the
       flask with  a strong  brief reverse  mixing action,  and  quickly  remove
        1 mL  of cell culture from the flask with a sterile  pipet.
     3. Place the aliquot  in  a counting beaker,  and add 9 mL  (or  19 mL) of
       electrolyte solution  (such  as  Coulter ISOTONR).
     4. Determine the cell density  (and MCV,  if  desired).

 11.7.2.2  Manual microscope counting  methods

 11.7.2.2.1   Cell counts may be determined using a Sedgwick-Rafter,
Palmer-Maloney, hemocytometer,  inverted microscope, or similar methods.  For
details on microscope counting methods, see APHA 1985 and Weber 1973
Whenever feasible, 400 cells-per replicate are counted to obtain + 105S
precision at the 95* confidence level.  This method has the advanTage  of
allowing for the direct examination of the condition of the cells.

11.7.3  Chlorophyll Content

11.7.3.1  Chlorophyll may be measured in-vivo fluorometrically, or in-vitro
either fluorometrically or spectrophotometrically.  In-vivo fluorometric
measurements are recommended because of the simplicity and sensitivity of the
technique and rapidity with which the measurements can be made (Rehnberg et
al., 1982)            ,-

                                       87

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The measurements are made as follows:

    1. Adjust the "blank" reading of the fluorometer using the filtrate from
       an equivalent dilution of effluent filtered through a 0.45 urn particle
       retention filter.
    2. Mix the contents of the test culture flask by swirling successively in
       opposite directions {at least three times), and remove 1 ml of culture
       from the flask with a sterile pipet.
    3. Place the aliquot in a small disposable vial and record the
       fluorescence as soon as the reading stabilizes.  (Do not allow the
       sample to stand in the instrument more than 1 min.)
    4. Discard the sample.

11.7.4  Turbidity (Absorbance)

11.7.4.1  A second rapid technique for growth measurement involves the use of
a spectrophotometer to determine the turbidity, or absorbance, of the cultures
at a wavelength of 750 rim.  Because absorbance is a complex function of the
volume, size, and pigmentation of the algae, it would be useful to construct a
calibration curve to establish the relationship between absorbance and cell
density.

The algal growth measurements are-made as follows:

    1. A blank is prepared as described for the fluorometric analysis.
    2. The culture is thoroughly mixed as described above.
    3. Sufficient sample is withdrawn from the test flask with a sterile pipet
       and transferred to a 1- to 5-cm cuvette.'
    4. The absorbance is read at 750 nm and divided by the light path length
       of the cuvette, to obtain an "absorbance-per-centimeter" value.
    5. The 1-cm absorbance values are used in the same manner as the cell
       counts.

11.7.5  Biomass

11.7.5.1  The results of algal growth potential tests are commonly expressed
in terms of biomass (mg dry wgt organic matter/L).  Algal biomass can be
calculated from cell counts and mean cell volumes, or can be measured directly
by gravimetric methods,

11.7.5.2. Biomass calculated from Cell Counts and Mean Cell Volumes

Algal biomass is calculated as follows:

       Dry Weight (mg/L) 3  Cells/L X MCV(um3) X mg organic matter/um3

       Where: MCV a either:

       1. The "measured" or "actual" cell volume, such as determined with
          a Coulter Counter or determined by microscopic examination, or
                                     88

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       2. When actual measurements are not available, a value of 60 uro3
          Is Used as an estimate of the MCV.  A standard value of 3.6 X
          10-10mg is used for the weight of organic matter/un»3.

    If the cell count is 1,000,000 cells/ml:

     Bioraass (rag/L)  »  1,000,000 cells/ml. X 1000 mL/L X 60 um3/cell X

                        3.6 X 10-10 mg/um3

                     *  21.6 mg/L


11.7.5.3  Biomass by Direct, Gravimetric, Dry Weight Measurements

11.7.5.3.1  Direct, gravimetric methods of measuring biomass are
appropriate where the harvestable biomass per test flask is greater than
10 mg dry weight.  This condition is met where the cell density is equal
to or exceeds 5,000,000'cells/ml.  This cell density would not ordinarily
be achieved in a 96-h test, but would be applicable with a 14-day test.

11.7.5.3.2  If the cell density is large enough to warrant use of the
gravimetric method, proceed as follows, treating each flask separately:

    1. Centrifuge the entire contents-of each flask at 1000 X g for 5 min.
    2. Decant the supernatant (do not retain more than 10 mL of culture
       medium with the cells).  Note: Caution must be exercised to avoid
       disturbing the sedimented cells when decanting the supernatant.
    3. Resuspend the cells in 10 ml distilled water.
    4. Centrifuge and decant, as in (2) above.
    5. Transfer the sedimented cells from each flask to a separate weighed
       crucible or weighing pan.
    6. Dry overnight at 70°C.
    7. Cool in a desiccator and weigh to the nearest 0.1 mg.
    8. Report the dry weight in mg/L.

11.7.5.3.3  The cells may .also be concentrated and dried on 0.45-um pore
diameter membrane filters or on equivalent glass fiber or other filters,
as follows:

    1. Dry the filters for 2 h at 70°C (temperatures above 75°C may
       cause the pores to close in membrane filters.
    2. Allow the filters to cool in a desiccator for at least 1 h before
       weighing.
    3. Filter the contents of the test flask using a vacuum of 380 mm of
    -  mercury, or a pressure not to exceed one-half atmosphere.
    4. Rinse the filter funnel with 50 mL of distilled water using a wash
       bottle, and allow the rinsings to pass through the filter.  The
       rinse serves to transfer all the algae to the filter and washes the
       nutrient salts through the filter.
    5. Dry the filters overnight at 70°C (to constant weight), cool in a
       desiccator for 1 h, and weigh to the nearest 0.1 mg.

                                     89

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11.8  SUMMARY OF TEST  CONOITONS

11.8.1  A  suriaary of test  conditions  is  listed  in  Table  3.

11.9  ACCEPTABILITY OF TEST RESULTS

11.9.1  The test results are acceptable  if the  algal cell density  in the
control flasks exceeds 106cells/mL at the end of the test,  and does not vary
more than  10X among replicates.

12.  CALCULATIONS

12.1  TOXICITY DATA

12.1.1  The data can be analyzed by Dunnett's Procedure  or  Probit Analysis.
The results of the toxicity test are  expressed  as  an NOEC and/or EC!
(threshold effect concentration).  The chronic  value can also be determined if
desired.               ;  .    - .

12.1.2  The NOEC and LOEC  (MATC), and chronic value are  based on comparisons
of the growth of the control  organisms with each of the  toxicant
concentrations, using  Dunnett's Test.

12.1.3  The statistical tests described  here must  be used with a knowledge of
the assumptions upon which  the tests  are contingent,  tests for normality and
homogeneity of variance are included  in  the Appendix.  The  assistance of a
statistician is recommended for analysts who are not proficient in statistics.

12.1.3  Dunnett's Procedure:

12.1.3.1  Dunnett's Procedure (Dunnett,  1955) includes an analysis of variance
(ANOVA) followed by a  comparison of each toxicant  concentration mean with the
control mean.  The error value calculated in the ANOVA is used in the
comparison of the control and treatment means.  The computer program listed in
the Appendix generates output which includes an ANOVA table, a statement about
each treatment mean that can be used  to  identity the NOEC and LOEC, and the
minimum difference between  treatment  and control means that can be detected as
statistically significant.   Dunnett's Procedure is used when the assumptions
of normality-and homogeneity of variance are met.  If they are not met,
Steel's Many-One Rank Test  is used.-

12.1.3.2  The sample set of cell counts  shown in Table 4 were transformed to
logiO to help meet the assumptions for normality and homogeneity of
variance.  The logs were input to the Dunnett's program  listed in the
Appendix.

12.1.3.3.  The results of the analysis of variance of the log transformed data
from Table 4 are shown in Table 5, and indicate a statistically significant
difference in survival among cadmium concentrations.  The computer output for
the -comparison of treatment means with the control mean is shown below:
                                       90

-------
    THERE IS NO SIGNIFICANT  DIFFERENCE  BETWEEN  CONCENTRATION  2
    (5 US CO/I) AND CONTROL.

    THERE IS A SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 3
    (10 US CD/L) AND CONTROL.

    THERE JS A SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 4
    (20 UG CD/L) AND CONTROL.

    THERE IS A SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 5
    (40 US CD/L) AND CONTROL.

    THERE IS A SIGNIFICANT DIFFERENCE BETWEEN CONCENTRATION 6
    (80 UG CD/L) AND CONTROL.

12.1.3.4  The NOEC and LOEC, as determined from the Dunnett computer
analysis, were 5 ug Cd/L and 10 ug Cd/L, respectively. (Note  that the
Ounnett program considers the control as Concentration 1, so  that
Concentration 2 in the output is 5 ug Cd/L in the test).  The MATC was
5 - 10 ug Cd/L

12.1.3.5  For this set of data, the minimum difference between the control
mean and a treatment mean that can be detected  as statistically
significant is 225,339 cells/mL.  This represents a 18.151 reduction in the
response from the control.

12.1.3.6  The chronic value is determined by calculating the  geometric
mean (GM) of the NOEC and LOEC, as follows:

    Logic NOEC  =  Logic 5.0  =  0.69897
    Logio LOEC  »  Logic 10.0 =  1.00000
    ChV  =  Antilog (0.69897 + 1.0000)/2  =  Antilog 0.8495
    ChV  =  7.07 ug Cd/L

12.1.4  Probit Analysis

12.1.4.1  Although the assumptions for Probit Analysis are not met in the
classical sense because of the very nature of the algal growth data, the
analysis is used to obtain an estimate of the EC1.  To carry out the
Probit Analysis, use the growth response data,  such as cell counts,
in-vivo chlorophyll fluorescence, or absorbance, for each set of three
replicate flasks in a given treatment.  The special Probit program listed
in the Appendix uses the algal  count data, determines the mean,  and
converts it to an "inhibition proportion" using the following formula:
    Where: C = The mean growth in the control flasks
           T = The mean growth at a given effluent
               concentration.

                                     91      :

-------
12.1.4.2  The cell counts were entered Into the "Algal" Probit program
listed 1n th« Appendix.  The EC1 was found to be 2.27 ug Cd/L, with upper
and lower confidence limits of 3.42 and 1.20 ug Cd/L, respectively, at
P * 0.05.  An example of how the data are entered in the program and the
program output are provided In the Appendix.

12.2  BIOSTIMULATION

12.2.1  Where the growth response in effluent (or surface water) exceeds
growth In the control flasks, the percent stimulation, S(X), 1s calculated
as shown below.  Values which are significantly greater than the control
indicate a possible degrading enrichment effect on the receiving water
(Walsh, et al., 1980b):
                             S(X) - T - C
                                            X 100
13.  TEST PRECISION AND-ACCURACY

13.1  PRECISION

13.1.1  Data from repetitive 96-h toxicity tests, conducted with three
reference toxicants, are shown in Table. 6.  The relative standard
deviation (coefficient of variation) of the LCls ranged from 47% to 83%.

13.2  ACCURACY

13.2.1  The accuracy.of toxicity tests can not be determined.
                                     92

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TABLE 3. SUMMARY OF RECOMMENDED TEST CONDITIONS FOR THE ALGAL GROWTH TEST
    1. Test type:
    2. Temperature:
    3. Light quality:
    4. Light intensity:
    5. Photoperiod:
    6. Test flask size:
    7. Test solution volume:.
    8.. Age of stock culture
        used for inoculum:
    9. Initial cell density:
   10. Number of replicates
       per concentration:
   11. Shaking rate:

   12. Dilution water:
   13. Dilution factor:
   14. Test duration:
   15. Effect measured:
   16. End point(s):
Static
24 + 2°C
"Cool white" fluorescent lighting
86 + 8.6 uE/m2/s (400 + 40 ft-c)
Continuous illumination
125 mL or 250 mL
50 mL or 100 mL

4 to 7 days
10,000 cells/mL
3

100 cpm continuous, or twice daily
by hand
Algal stock culture medium without
EDTA, or surface water
Approximately 0.3 or 0.5
96 h
Growth (cell  counts, chlorophyll
fluorescence, absorb.ance, biomass)
EC1, NOEC,  S(»)
                                    93

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    TABLE 4. SAMPLE DATA FROM ALGAL TOXICITY TEST WITH CADMIUM CHLORIDE
Toxicant
Concentration
(uq Cd/L)
0 (Control)

•
5


10


20


40


80


Growth
Response:
Cells/mL
ToTSo"
1209
1180
1340
1212
1186
1204
826
628
816
493
416
413
127
147
147
49.3
40.0
44.0
Cells/mL
1000
(Logic)
3.082
3.072
3.127
3.084
3.074
3. .081
2.917
2.798
2.912
2.693
2.619
2.616
2.104
-2.167
2.167
1.693
1.602
1.643
Percent
Inhibition
of Growth
!(*)

0


3.4


39.1


64.5


88.7


96.4

    TABLE 5. ANALYSIS OF VARIANCE OF CELL COUNT DATA IN  TABLE 4
             TRANSFORMED TO
Source
Among
Within
Total
OF
5
12
17
Sum of Squares
4.995
0.021
5.016
Mean Square
0.999
0.002

Calculated Tabular
F PQ.05
560.183* 3.11


Significant at P » 0.05.
                                    94

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                                    101

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                                    104

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                              APPENDIX

A.   Validating Normality and Homogeneity of Variance
     Assumptions	   106
     1. Introduction	   106
     1. Test for Normal Distribution of Data  .	    106
     2. Test for Homogeneity of Variance	   109
8.   Arc Sine Square Root.Transformation	   Ill
C.   Ounnett's Procedure   ....... 	   113
     1. Manual Calculations  . . . . «,	   113
     2. Computer Calculations  .-,-.".	   118
D.   Steel's Many-one Rank Test	   132
E.   Fisher's Exact Test ......	   135
F.   Probit Analysis	   144
     1, Probit Analysis of Fathead Minnow Embryo-larval
        Test Data	   144
     2. Probit Analysis of Algal Growth Test Data  	   154
                                105

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                                 APPENDIX A

        VALIDATING NORMALITY AND HOMOGENEITY OF VARIANCE ASSUMPTIONS1
1.   INTRODUCTION

1.1  Ounnett's Procedure  1s  a parametric procedure  and  1s based on the
assumptions that the observations are  Independent  and  normally
distributed, and that the variance of  the observations is homogeneous
across all toxicant concentrations and the control.  These assumptions
should be checked prior  to  using Dunnett's Procedure,  to determine if they
have been met.  Tests for validating the assumptions are provided in the
following discussion.  If the tests fail (if the data  do not meet the
assumptions), a non-parametric procedure such as Steel's Many-One Rank
Test may be more appropriate.  However, the decision on whether to use
parametric or non-parametric tests may "be a judgement  call, and a
statistician should be consulted in selecting the  analysis.

2. TEST FOR NORMAL DISTRIBUTION OF DATA

2.1  A formal test for normality is the Chi-Square Sdodness of Fit Test.
This test compares the observed sample distribution with a normal
distribution.  An example of the test -is provided  below.

2.2  The example uses mortality data from the fathead  minnow larval
survival and growth test with sodium pentachlorophenate (NaPCP) listed in
Section 10, and is the same data used  in the discussion of the homogeneity
of variance determination in Appendix  A.3 and the  Dunnett's Procedure in
Appendix C.  The data used  in the Dunnett's Procedure  has been arc sine
square root transformed, and it is the transformed data which will be
tested for normality.  The  transformed data and the mean and standard
deviation of the observations at each  toxicant concentration, including
the  control, are listed  in  Table A.I.

2.3  The first step of the  Chi-Square  Goodness of  Fit  Test is to
standardize the observations by subtracting the mean from each observation
and  dividing the difference by the standard deviation.  The standardized
observations are listed  in  Table A.2.

2.4  Form five cells as follows:  < -1.5;  -1.5 to  <  -0.50;  -0.50 to
0.50; > 0.50 to 1.5; >1.5.  Tabulate  the number of standardized
observations which fall  into each of the five cells.   These are the
observed frequencies, f-j.   The expected frequency, FT, is found by
multiplying the area under  the standard normal curve over the ith cell
limits by the total number  of standardized observations, N.
^Prepared by John Menkedick and Florence Kessler, Computer Sciences
Corporation, 26 W. St. Clair St., Cincinnati, Ohio 45268; Phone
513-568-7968.

                                     106      -;

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TABLE A.T.  ARC SINE SQUARE ROOT TRANSFORMED DATA FOR CHI-SQUARE TEST
NaPCP Concentration
Replicate
1
2
3
4
Total -.
Mean
Si
i
Control 3
1.412
1.412
1.249
1.249
5.322
1.330
0.0941
1
TABLE A.2.
1.107
1.107
1.412
1.107
.4.733
1.183
0.1524
••' 2
5
1.249
1.412
1.412
1.412
•5.485
1.371
0.0815
3
EXAMPLE OF CHI-SQUARE TEST
7
1.249
1.249
1.107
1.412
5.071
1.254
0.1246
4
(ug/L)
11
0.991
1.249
1.412
0.785
4.437
1.109
0.2769
5

16
0.685
0.580
0.685
0.464
2.414
0.604
0.1054
6
FOR NORMALITY:
STANDARDIZED OBSERVATIONS
NaPCP Concentration
Replicate
1
2
3
4
Control
0.8714
0.8714
- Q.8608
• 0.8608
3
- 0.4987 -
- 0.4987
1 .5026
- 0.4987
5
1.4969 -
0.5031
0.5031 -
0.5031
7
0.0401
0.0401
1.1798
1.2680
(ug/L)
11
- 0.4261
0.5056
1 .0942
- 1.1701

16
0.7685
- 0.2277
0.7685
- 1.3283
                                  107

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2.5  For this exauple, N » 24.  The areas for each cell, the observed
frequencies, and the expected frequencies are given in Table A.3.


           TABLE A.3.  EXAMPLE OF CHI-SQUARE TEST FOR NORMALITY:
                       ACTUAL AND EXPECTED FREQUENCIES
Cell
Interval
i
Area
Fi
f' '
<-1.5 -1.5 to <-0.5
1 2
0.067 0.242
1.608 5.808
0 6.
-0.5 to 0.5
3
0.382
9.168
7
>0.5 to 1.5 :
4
0.242
5.308
10
>1 5
5
0.067
1.608
1
2.6  The Chi-Square Goodness of Fit Test statistic (X2) is calculated as
follows:                            .
                   2s           V
                  X2 -  S  (f, -  FJ2
                                       -
2.7  For the data in the example:


 2   (0 - 1.608}2 + (6 - 5. 80S)2 + (7 - 9.168)2 + (10 - 5. 80S)2 + (1 - 1.608)2

X  *  1.608           5.808          9.168            5.308         TISS


   * 5.3825


2.8  The decision rule for this test is to compare the critical value,
X2, with four degrees of freedom ( No. of cells - 1) and an alpha of
0.01, to the computed X2.  If the computed value exceeds the critical
value, conclude that the data are not normally distributed.  For this
example, the critical value is 13.28.  The calculated value, 5.3825, does
not exceed th€ critical value.  Thus, the conclusion of the test is that
the data are normally distributed.

2.9  In general, if the data fail the test for normality, a transformation
such as to log values may normalize the data.  After transforming the
data, repeat the Chi-Square Goodness of Fit Test for normality.
                                     108

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3.  TEST FOR HOMOGENEITY OF VARIANCE .

3.1  For Qunnett*s Procedure, the variances of the data obtained from each
toxicant conctntration and the control are assumed to be equal.
Bartlett's Test is a formal test of this assumption.  In using this test,
it is assumed that the data are normally distributed.  An example of how
this test is performed is provided below:

3.2  The data used in this example are mortality data from a fathead
minnow larval survival and growth test, and are the same data used in
Appendix C.  Since Dunnett's Procedure is performed with arc sine
transformed data, Bartlett's Test is performed with the same transformed
data.  These data are listed in Table A. 4, together with the calculated
variance for the control and each toxicant concentration.

3.3  The test statistic for Bartlett's Test (Snedecor and Cochran, 1980)
is as follows:


                  v[a(ln S2) - £ In sf]
Where:  v *   Degrees of freedom for. each toxicant concentration and control
        a »   Number of levels of tox-icant concentration including the
              control
       32 s   The average of the individual variances

        C »   1 +C(*H)/3av].

       In =   Loge
3.4  For the data in this example, v = 3, a = 6, U2 » 0.0236, and
     C = 1.1296.  The calculated B value is:


                     3 [6(ln 0.0236) - Z In S?]
                                 1.1296

                     3[6(-3.7465) - (-24.7529)]

                                1.1296

                     6.0390
                                     109

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3.5  Since Bis approximately distributed as Chi Square with a - 1 degrees
of freedom whin the variances are equal, the appropriate critical value
for the ttst is 15.09 for a significance level of 0.01.  Since B < 15.09,
the conclusion is that the variances are equal.


    TABLE A.4  DATA USED IN  BARTLETT'S  TEST FOR HOMOGENEITY OF VARIANCE
NaPCP Concentration (ug/L)
Replicate
1
2
3
4
Total
Mean
Si 2
i
Control
1.412
1.412
1.249 1
1.249
5.322
1.330
0.0088
1
3
1.107
1.107
' -1.412
1.107
4.733-'
1.183
0.0232
2
5
1.249
1.412
"1.412
1.412
5.485'
." 1.371
0.0066
3
7
1.249
1.249
1.107 '
1.412
5.071
1.254
0.0155
4
11
0.991
1.249
1.412
0.785
4.437
1.109
0.0767
5
16
0.685
.0.580
0.685
0.464
2.414
0.604
o.om
6
                                    no

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b.  For RP * 0 (no mortality), the following adjustment is made:
       Angle (in radians) » Arc Sine (l/4N)0-5
       Where: N * Number of animals/treatment
       Example; If 20 animals are used, .
      "Angle « Arc Sine (1/80)0-5
             - Arc Sine 0.1118
             » 0.1120 radians
c.  For RP - 1.0 (10031 mortality):
     Angle * 1.5708 radians - (radians for RP » 0)
    Example: Using above value
     Angle - 1.5708:- 0.1120
           * 1.4538  radians
                                 112

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                                  APPENDIX B

                     ARC SINE SQUARE ROOT TRANSFORMATION1
 1.   Arc  Sine transformation consists  of determining the angle (in radians)
 represented by a sine value.  In the  case of arc sine square root
 transformation of mortality data,  the proportion of dead (or affected)
 organisms  is taken as the sine value, the square root of the sine value is
 determined,  and the angle (in  radians)  for the square root  of the sine
 value  is determined.  Whenever the proportion dead is 0 or  1,  a special
 modification of the arc  sine square root transformation must be used
 (Bartlett,  1937).  An explanation  of  the arc sine square root
 transformation and the modification is  provided below.

 2.   Calculate the response proportion (RP)  at-each effluent concentration,
     where:

     RP  «  (number of dead or "affected"  organisms)/(initial  number).

     Example;  If 8 of 20  animals  in  a  given  treatment  die:

       •  RP  -  8/20
            .-  0.40

3.  Transform  each RP  to  Arc Sine,  as follows:

     a.  For  RP  *  > 0   to  < 1:

        Angle  (radians) * Arc Sine

           Example:  If RP » 0.40,

           Angle  » Arc Sine  (0.40)°-5
                 * Arc Sine 0.6325
                 * 0.6847 radians
Vrora Peltier and Weber (1985).


                                     m

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                                 APPENDIX C

                             OUNNETT'S PROCEDURE
1. MANUAL CALCULATIONS1
1.1 Ounnett's Procedure is used to compare each concentration mean with
the control mean to decide if any of the concentrations differ from the
control.  This test has an overall error rate of alpha, which accounts for
the multiple comparisons with the control.  It is based on the assumptions
that the observations are independent and normally distributed and that
the variance of the observations is homogeneous across all concentration
and control.  (See Appendix A for a discussion on validating the
assumptions).  Ounnett's Procedure uses & pooled estimate of the variance,
which is equal to the error value calculated in an analysis of variance.

1.2  The data for this example are mortality data from a fathead minnow,
larval survival and growth test.  Since the data are expressed in
proportions, a transformation of the square root of the proportion to an
arc sine value is required (See Appendix 8.)  A table of the raw data
(Table C.I) and transformed data (Table C.2) are provided below.


      .  TABLE C.I. PROPORTIONS OF SURVIVING TEST ORGANISMS.


      Concentration         i                Proportion Surviving
      (ug NaPCP/L°)                          in Replicate Chambers

Control
3
5
7
11
16

1
2
3
4
5
6
A
1.00
0.30
0.90
0.90
0.70
0.40
3
1.00
o.ao
1.00
0.90
0.90
0.30
C
0.90
1.00
1.00
0.80
1.00
0.40
0
0.90
o.ao
1.00
1.00
0.50
0.20
^Prepared by John Menkedick and Florence Kessler, Computer Sciences
Corporation, 26 W. St. Clair St., Cincinnati, Ohio 45268; Phone
513-568-7968)

                                     113     :•

-------
      TABLE C.2. ARC SINE TRANSFORMED DATA FOR  OUNNETT'S  PROCEDURE
NaPCP
(ug/L)
Control
3
5
7
n
16
Cone
(D
1
2
3
4
5
6
Transformed Data
(Arc Sine In Radians))
Replicate
A
1.412
1.107
1.249
1.249
1 0.991
0.685
B
1.412
1.107
1.412
1.249
1.249"
0.580
C
1.249
1.412
1.412
1.107
1.412
0.685
0
1.249
1.107
1.412
1.412
0.785
0.464
Total
Ti
5.322
4.733
5.485
5.017
4.437
2.414
Mean
Y1
1.330
1.183
1.371
1 .254
1.109
0.604
1.3  One way to obtain an estimate of-.the  pooled  variance  is  to construct
an ANOVA table including all sums of  squares,  using  the following
formulas:

Total Sum of Squares: TSS •  2 Y2. -   G2/N
                             ij  7J

Between Sum of Squares:  SSB 3  2 T2/n.  -   G  /N

Within Sum of Squares: SSW * TSS - SSB
    Where: G » The grand total  of all sample observations; G  » 2 T^
           N » The total sample size; N =  2  n.                1
           *
               The number of replicates for  concentration  "1".
          T.I » The total of the replicate measurements for concentration  "i".
         Y.J.J * The jth observation for  concentration  "i".
          ' j
1.4  Calculations:
Total Sum of Squares: TSS » 2 Y?.  -  G2/N
                            33.302  -  (27.408)/24
                            2.002           ;".
                                        114

-------
Between Sum of Squares:  SS8 » E T?/n. -  G2/N
                               1
                              - 32.875 - (27.408)2/24
                              * 1.S75

Within Sura of Squares: SSW » TSS - SS8,
                           » 2.002 - 1.575
                           - 0.427
1.5  Prepare the ANOVA table as follows:
Source

Between
Within
Total


b
N
N
OF

*-l
- b
- 1
Sum of Squares (SS)

SSB
SSW
TSS .-
Mean Square(MS)
.(SS/DF) .
s| » SSB/(b-l)
S2 » SSW/(N-b)

F

S2/S2
W


    *Where b » Number of different concentrations, including the control,
1.6  The completed ANOVA table for this data is provided below:


     TABLE C.3. COMPLETED ANOVA TABLE FOR OUNNETT'S PROCEDURE
Source OF
Between . 6 -- 1 » 5
Within 24 - 6 » 18
SS
1.575
0.427
MS
0.315
0.024
F
13.125

Total           23       '  •  .  2.002
                                    115

-------
1.7  To perfora the individual comparisons, calculate the t statistic
for etch concentration and control combination, as follows:
   •Where: ?i   *  Mean for each concentration
           TI   *  Mean for the control
           Sw   *  Square root of the within mean square
           ni   »  Number of replicates in the control.
           n^   »  Number of replicates for concentration "1".

1.8  Table C.4  includes the calculated t values for each concentration
and control combination.
                     TABLE C.4.  CALCULATED T VALUES.
          Concentration
          (ug NaPCP/L)
3
5
7
11
16
2
3
4
5
6
1.342
- 0.374
0.694
. 2.108
6.630
1.9  Since the purpose of the test  is only to detect a decrease in
survival frora the control, a one-sided test is appropriate.  The
critical value for the one-sided comparison, with an overall alpha level
of O.OS, 18 error degrees of freedom, and 5 concentrations excluding the
control, 1s 2.41 (See Table C.S).   Comparing each of the calculated t
values  in Table C.4 with the critical value, the 16 ug NaPCP/L
concentration is found to have significantly lower survival than the
control  (6.630 > 2.41).  Thus the NOEC is 11 ug NaPCP/L.
                                    116

-------
1.10  To quantify the sensitivity of the test, the minimum significant
difference (MSO) may be calculated.  The formula  is as follows:
Where: -d
      S*
       n
For example:

       MSO »
                          MSD » d 3^(17^) + (1/n)

                  Critical value for the Qunnett's Procedure
                  The square root of the within mean square
                  The number of replicates at each concentration,
                    assuming an equal number of replicates at all
                    treatment concentrations
                  Number of replicates in the control
             2.41 (0.1S5)[V(l/4)
             2.41 (0.155)(0.707)
             0.264 ;
                                        (1/4)1 a 2.41 (0.155)(
1.11  The MSD (0.264) is in transformed units.  To determine the MSO in
terms of percent survival, carry out the following conversion:

1.11.1.  Subtract the MSO from the transformed control mean.

                 1.330  - 0.264 * 1.066

1.11.2; Obtain untransformed values for -the control mean (1,3305) and the
difference (1.0665) obtained in Step 1.

                  [Sine (1.330)]2 = 0.943
                  [Sine (1.066)]2 * 0.766

1.11.3. The untransformed MSD (MSDU) is determined by subtracting the
untransformed values obtained in Step 2.

                  MSDU * 0.943 - 0.766 = 0.177

1.11.4  For this set of data, the minimum difference between the control
mean and a concentration mean that can be detected as statistically
significant is 0.177.  This represents a decrease in survival of 19% from
the control.     "          •
                                     117

-------
2. COMPUTER CALCULATIONS

2.1  Tli1s computer program incorporates two analyses: an analysis of
variance (ANOVA), and a multiple comparison of treatment means with the
control mean (Ounnett's Test).  The ANOVA indicates whether there is a
significant difference between the results obtained at different toxicant
concentrations.  The Dunnett Test indicates which toxicant concentration
means (if any) are statistically different from the control mean.  The
program also gives the minimum difference between the control and
treatment means that could be detected as statistically significant.  The
multiple comparison is based on Ounnett, C. W., 1955, "Multiple Comparison
Procedure for Comparing Several Treatments with a Control," J. Araer.
Statist. Assoc. 50:1096-1121.  Tables for one-tailed "F" and Dunnett's "t"
(P » 0.05) are included in the program, but are limited to values for
eight concentrations, including the control, and six replicates per
concentration.  If the test design exceeds these limits, it is necessary
to consult the "t" and "F" tables listed following the program.

2.2  The program was written in FORTRAN PLUS IV v.3, by James Dryer, and
runs on the Digital Equipment Corporation, POP 11/70 computer under IAS
version 3.1.  Machine readable copies of the program, and assistance in
running it, can be obtained by contacting James Dryer, EMSL-Cincinnati
Newtown Facility (FTS 778-8350; comm'l 513-527-8350).

2.3  Description,of Data Input and Output from the Computer Program

2.3.1  Data Input    '                                                    •

2.3.1.1  Cell growth data from a Selenastrum toxicity test, listed in
Table 4, Section 14, were used to illustrate the data input process and
the output provided by the computer program.  As shown below, the program
prompts the operator for the following information:

    1. The type of transformation to be used with the data.
    2. The number of replicates at each concentration.
    3. The values (cell growth) obtained from each replicate toxicant
       concentration.

2.3.1.2  Several transformations are available in the program.
Transformation option "3", conversion to log-jo, was used in the example
provided.  Six concentrations, each with three replicates, were used in
the test.  The control is considered as Concentration 1.

2.3.2  Program Output

2.3.2.1  The output from the analyses includes:

    1. A table of the original data (cell growth) input to the program.
    2. An ANOVA table listing the calculated "F" and tabular "F" values.
    3. A series of statements regarding the results of each sequential
       comparison of a toxicant concentration mean with the control mean.
                                     118

-------
2.3.2.2   The calculated F from the ANOVA j,s compared with the tabular F
value where P * 0.05, and OF  » 5,12.  The" calculated F (560.183)  is
larger than the tabular F (3.11),  indicating that  the survival is
significantly different at  the different toxicant  concentrations.

2.3.2.3   The output from the  Qunnett sequential  comparisons indicates
that there  is a significant difference between Concentration 3 and the
control  (Concentration 1).  On the basis of these  results, the NOEC  is
Concentration 2.                                                     •

2.3.3  Computer Generated Listings of Input and  Output from the Computer
Program  for Dunnett's Test  ana Analysis of Variance
    BUNNETTS   TEST


 IF TOO MEED INSTRUCTIONS»TYPS 1.  OTHCRyiSS.TTPF 0-1

 ANOVA-4IITH gUNNCTTS COMPARISON OP EACH  CONCENTRATION (ISAM
 V3 THE CONTROL MEAN*


  A ONE-SIDED »T« AT *SZ IS USED IN ALL "CASES.


  THE FOLLOWING TRANSFORMATIONS ARE AVAILABLE TO USE ON
  THE VALUES:

  NUNBER     TRANSFORMATTON
    0        NONE
    1        SQUARE ROOT(X)
    3        LOO 10
    3       4
            ARCSINOO.  RTCX+1)/CN+1>J>/7
    6        ARC3ZN((X>nO.S>
TRANSFORMATION NUMBER • 3
AVERAGE NUMBER OF TFST ORGANISMS AT  WGINNTNG PER CONCENTRATION « 100,
INCLUDING CONTROLf NUMBER OF CONCENTRATIONS * 4
NOTE: BESTN WITH CONTROLCCONCENTRATION NUMBER i>  AND ENTER  IN ASCENDING ORDER.


NUMBER OF REPLICATES IN CONCENTRATION NUMBER   1
* 3
NUMBER OF REPLICATES IN CONCENTRATION NUMBER   ?
- 3
NUMBER OF REPLICATES IN CONCENTRATTON NUMBER   3
- 3
NUMBER OF REPLICATES IN CONCENTRATION NUMBER   4
• 3
NUMBER OF REPLICATES IN CONCENTRATION NUMBER   S
- 3
NUMBER OF REPLICATES IN CONCENTRATION NUMBER   *
- 3
                                      119

-------
2.3.3  Cosput**" generated  Listings  of Input  and Output from the  Computer
FrogrM  for  Dunnttt's  Procedure (Continued)
                      TEST OATA FWH IW1UIIUM. RtPUCATEJ.


                 MTEl KCXMM. MIHT HtST BE USED IN


                       OF ancarnunw unto  t -
                120f.     .   ,     '           '.'
                •VMOJT* tf CONCSHTHMIOI MJNtER .1 -

                tilt.
                •VMJUC- tF COKBtmtnw MJNIER  2

                1212.
                "V*UJC- ^ COHCEHIIWriOl KU1IER  2
                tit*.  •
                •VMJK" IF COKZrmATiaN ItJHISt  2

                1204.
                •UILUC- IF COKStTMTtUN HJHISt  3~

               ' 82*.  '
                -V«JJ£" IF CONCS4TRITHW IU11ER  3

                421.
                -VMJJC" IF CJWSHTRiTtW MJNIER  3
                     - OF coNcemwrioN KUHISI  4
                4t3.
                *VMJJ£M IF eaicsfTiMriaN IUIIER  4

                41*.
                "VtLUt" IF COKeiTRATZBN RMIG?  4

                413.
                       IF CONCStTRATIOl HU1IER  S
                127.
                -v*LUt" jf eoNCENTmrioi IUMIER  s
                •VUJUl" IF COKElTOmiN HHISt  S
                  147.
                -VtUJt" V C9NOKT1ATION MJUEX  6

                44.                       ' '  .
                -VALUE" IF coNcamwnoi HWIIER  6

                4».
                •VMOJE- IF CGNCEHTMTItH IUUER  "4

                4».3                      —
                                             120

-------
2.3.3   Computer  Generated  Listings of Input  and Output from Computer
Program for Qunnett's Procedure  (Continued)
                   tESILTS   OF   36 I Ue I T I  * I   COMPARISONS
                            II S I N •   THE   D U » »  E T I S   TEST
                  FBI THIS SET W MTA, TIE IIMIKM OtFFERElCE THAT CAI BE
                  JETECTEB AS STATISTICAL!.! S1S1IITICJWT IS     223.33* .
                  THIS REFftESEftTS A  IS.tZ KESUCTION IN THE MEAN
                  lEsrtmse nan THE antTsou.
                  T •  2.39

                 TWW3 NO SIBNiriONT OIFFCREICE 3ETWEN COKSITfttnON Z MO GOITRIL.

                 -> TUEU IS $I8«FICJ»*T 1IFFOEXCE BETUEEN COKartMnB* 1 US COITlttU

                 » THERE IS SI6KIFICMT 3IFFE8EXCE BETUKN COMCENTRrtTIOH 4 MO COITBB..

                 «> THEM IS SI8MIFICAHT BIFfESENCS IETUEEN CONCENT!MTIQI 3 AMI CONTROL.

                 » THERE IS SIBNIFICANT DIFFEREHCE lETBEEl CONCENTfMTIOl 4 Mil CONTtOL.


                                         I1PUT   DATA   TABLE
. tZOf.DM
1180.900
1340.000
1212.000
11 8*. 000
1204.000
82i.«06
428.000
814.000
493.800
414.0*0
413.08O
107.100
147.000
147.000
44.00O
40.010
49.30*
                              THANSFdRlEO   DATA   TASL.E

                  NOTE: TRAMSF08MTION HUMEX  3 UAS USES FOX  THIS SET OF OAtA

                      3.012      3.014     2.917      2.J93     2.104
                      3.072      3.074     2.7f«      2.419 '    2.147     !.
-------
2.4   Listing  of  Coaputar  Program  for  Ounnett's  Procedure
                                                              1,23)^131(30,22)

             C
                                        ,43)
             c
                                                    3,1.73,2.03,2.2,2.31,2.4,2.47,
                      1,1. 73.3.03,2.13,2.3,2.3»,2.4«,3. 31,1. 72.2.03,2.1S,2.3,2.3»,3.
                  *4«,2.31,1.72,2.03 ,2.1>,2.3,2.3«,3.43,2.3,1.71,2.a2,2.U,2.2»,2.3I
                  •,2.43,U,1.71,2.al.2.17,ZK2I,2J«,2.43,2.4«,l. 71,2.01, 2.17,2.27,
                  «3J«,3.43,2.4«fl. 71,3.01.2.17,2.27,2.33,2.42.2.47,1.71.2. ,2.14,2
                  •.27,2.3S,2.41^.4«,1.71,2.,2.K.2.2«,2.34,2.41.2.43,1.7,2.,2.H,
                  «2J*,2,3«,2.41,2.43,1.7,1.»,2.I3,2.23,2.33,2.4,2.43,1..7,1.»,2.
                  «13,3>21,3.33>3.4(3«43f1.7,i.3>,2.13,3.23,2'.33,3.4,2.43/
             C                       .  -      "   •
                  •3.M,3.«,3.2I,3.3,3.U,4.2<,3.M,3.C3,3.4«,3.37,3.29,4.9«.4.1,3.7
                  •l,3.4»,3.33,3.22,3.14,4,«4,3.9«,3.5»,3.3«,3.2,3.a»,3.01.4.73,3.W,
                  •3.«,3^2«,3.11.3..2.S2.4.«7,3.I,3.41.3.U,3.a2,2.32,2.«4,4.«,3.7«,
                  «3,3.24,3.Ql,2.««,2.74,2.«,4.43,3.3»,3^,2.9«,2.ai,2;7,2.«2,4.41,
                  •3.S,3.1«,3.»3,2.77,2.«4,2.5I,4J«,3.52,3.I3,2.9,2.74,2.«3,3.5S,
                  *4.33t3.49.3.1,3.*7.2.71.2,«,2.32.4.32,3.*7,3.a7,2.S4,2.S»,2.37,
                  «3,2.43,4.2«,3.4,3.01,2.7«,2.«2,2^S1,2.43,4.24,3.3«,2.M,2.7«,2.«,
                  •7.4S,2.41.4^3,3.37,2.M,2»74,2.»,2.47,2,3S,4.21,3.3S,2.3«,i.73,
                  «2.37,2.4«,2. 37,4.2,3.04,2^5,2. 71,2.3S,2.44,3.3«,4.1I,3.33,2.93,
                  n.7,2.34,2.43.2.33,4.17,3.32,2.32,2.«»,2.a3,2.«,2.34,4.1«,3.31,2.
                  •«l,2.«i,2ja.2.41.2^3,4.13,3.3,2.3,2.S7,2.31.2.4,2.32,4.14,3.3S,
                  «3.2«,2.»4,2.«3,i.4«,X.3«,2.2I,4.1,3.23f2.«3,2. 42,2.47,2.33,2.27,
                  •4.1,3.23,2.«3,2.a,2.4«,2.33,2.2«,4.0» ,3.24,2.84,2.41.2-43,2.34,
                  *7.23,4.0«,3.23.2.*4,2.«l,2.4S,2.J4,2.23,4.C»,3.22.2.a3,2.*,2.44,
                  «3.33, 2.24,4.07,3.22,2. *3,2.S9,2.44,2.32,2.24, 4. 0«,3.21,2.83,3.i»,
                  •J.43,2.33, 2.23, 4.0*,3.21,2-I2,2.M, 2.43, 2.31,2.23, 4.03,3.2.2.»1.
                  ^.S1^2.42,2.3,2.23,4.03,3.2,2.«1.3.S7,2.42,2.3,2.22.4.04,3.2,2.«
                               : oaeset, axt. n? TO rssar onczxnnasaa
                                      S '*•"-'

                                      •I" AT 95% IS ""« Bf All, CASZS. '


                             ! HttlCWIOT tSMBZOMOZCa ARE AWHABtZ TO OSE 3t>
                                   1  TRASSK
                            0        HENS1
                            1        SJOHZ
                            3        ICC 1000'
                                                      122

-------
2.4  Listing of  Program for  Ounnett's Procedure  (Continued)
                        s

                        •
                               MOf* J' 	
                                      'OX UHCS CBP SOt JSB *•!• AMD +1* r
            »nm 13    ____
             73 JQMffC* TRWWSMffiDBI SflflffH M ' /5)
             73 ;
                         .'«'Vm«730
                         i '«')MCOV 732,QBB
                BK3 t   " 	  ...--m.          jjmimifa.i;_

                MCDV 7rO3d
              7 Kunerta)	                       ^^      	
                B8B*> 'Kgftl 8BB8 MiilH 11 MTOi'ilfitl IM rffnftiilwtj IOOBI1) MO UU1R

                WOf,' •
                tn*»,' «	
                CO UL«2"L*CCMCX
               i
              9 :

             10 :

             ui
                         .
                00 3 I-1.CCW3.
                04
                »*(«
                03 4
              4
              3 " "I' )'<••'•
            soz THW, ' HOB: CBCDKL KHHT wsr ar asm or
                     * •
                oo 30,2-i.
                09 23^-1^(1)  .
            ta wnz(3,i3),i
             u Kmxec "VMBP1 or cMcwnaunf HOMER -,12, • -
                BOB IS
             13 ZOMff( «
                MSCPT 17,WZZ(X,J1
             17
              2
                                tO OO
                zrcnmauiQ. 's^ao TO SM
                                  TSS
                         * '7')00 TO 7S3
               (30 IS 23
            IM COB 7SO
            Tso lOMerxranai moex or •osr|CR»osw xr

               M3BT TSa.OBO
            732 KXMGT(I3.0)
                                     /3.14139Z7
                                            123

-------
— -  2.4-  Listing of Program for Dunnett's  Procedure  (Continued)
                                      VUSE (XBCSV tSMBKRODEII) •'
                      m ts.i-L.a3ta.
                      TWMCfn
                    IS ' **»f 1MIB
                               _
                       CD 90.I-l.CaCl
                      ig>*(i)
                    90 «_l_IIHli_B_
                             -i
                      ]?(0«.ar.33)(30 tO 5

                      17(<3.CT.71
-------
2.4  Listing of Program for Ounnett's  Procedure  (Continued)
             .   i«ejs*)«)

             s» **•&• '*••,*)

             ss» icaitttr4.a)

               * TOX stt
                        ' r- •,»
                       »,n

             SM wnsts,9is)
                                U3IHC   TBS  OOirifSTTS   T S 3 T*
             890 KMX '  T* MS.3)
                         a..'3 •
                TOT*,1 KR TOO SET OF CM3L SB MDOHK BQIBOBiaiE 1HW OH S*
             914
             913 RtMKTC  RXSdLTS  OF  SZgOZHTIXI.  O O K P A
               IRZSOV3M         '
                oo 4tt.z^.aaia
                7(AaB(lCCX)-M
-------
2.4   Llstinf of Program for Dunnett's  Procedure (Continued)
                             TJtAXSTOXMXO  0 A g A  TABU'
                            _ _ ____. ._
           TO* jcMec JOBS awnoHoaEH noon*,*),

              1 SB

                   •
                   I  •
                           .1
            MlOMfff  ««.«.•!»«,«, •««*!.•,3C,1   MDBCSJ.'

              1.3X.1    OtfCr  917(0.09)')
            u name HrnBr,43c.n,jg.2(n4.3,i»i)


               T
              1-
            J54 tOC*,' '
                    i •
            434 SOT
                                           126

-------
2.5   Table of Dunnett's "t" values.
                     TABLE C.5.   DUNNETT'S  "T"  VALUES1

^^w*





18
It
12
a
14
a
it
a
»
is
20
24
JO
4t
tc-
ii*
m


UM
U«4
UM
UM
US!
UH
l.M
UTS
UTT
UTS
1.75
UTS
UT4
UTS
UTS
UTS
UTI
UTO
UM
u«
UM
l.M


1.44
1.34
U2T
2.8:
1.1*
2.»
2.13
2.11
1.M
2.M
•S.OT
•2.M
!.«
1.04
2.01
2. OS
2.01
UM
un
UM
un
UM


1.M
2.U
1.U
2.41
1.2T
2.14
2.31
2.2S
2.1T
2. IS
2.14
1.29
2.21
2.21
2.20
tit
un
2. IS
2.13
2.U
2.M
2.M
(0*r

2.M
UT1
UM
ua
u»
2. IT
2.44
2.41
Ui»
U3T
2.3S
2.34
2.33
U3Z
U21
UJO
U2S
2.3S
2.2S'
2.12
2. IS
U14
•MUA4
• «.M
UM
i.n
2.71
UM
UM
2.M
2.11
UM
Ut*
U14
U~44
UU
2.41
U41
UM
U3t
2.3*
U33
U3I.
. *•**
*2.2S
ua
k.»

UM
un
UM
U74
UM
UM
UM
UM
UM
UU
UM
UM
U4S
U4«
U4T
U4«
UU
U40
U37
2.3S
U»
UM


2. IS
uos
UM
UU
un
UTS
un
UM
Ufl
UM
UJT
UM
UM
UU •
Utt
UJ1
UM
U4S
Utt
U3t
UJT
U34


U24
UOT
UM
UfT
uu
UTS
UTS
UM
UM
UM
un
Uft
UM
UM
UJT
UM
ua
UM
U4T
U44
U4I
UM


UM
U12
uot
un
UM
uat
' UTT
UT4
UTt
UM
UfT
UU
UM
Utt
Uil
UM
UJT
U14
UU
U4S
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ua
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-------

-------
                                   APPENDIX 0

                           STEEL'S MANY-ONE RANK TEST^

1.  Steel's Many-One Rank Test is a nonparametric test for comparing
treatments with a control.  This test  is an alternative to the Ounnett's test,
and may be applied to the data when the normality assumption has not been
met.  Steel's test requires equal variances across the treatments and the
control, but it is thought to be fairly insensitive to deviations from this
condition (Steel, 1959).  The tables for Steel's Test require an equal number
of replicates at each concentration.   If this is not the case, critical values
can be approximated by interpolation.

Z.  An example of the use of this test is provided below.  The test employs
reproduction data taken from Table 2, Section 13, Ceriodaphnia survival- and
reproduction test.  The reproduction data for 25X effluent were omitted from
the analysis because the results of Fisher's Exact Test indicated that a
significant proportion of the organisms died at that concentration.  Since
mortality is a significant effect, the remaining task was to determine if
there were significant differences in reproduction at the lower effluent
concentrations.

3.  For each control and concentration conbination, combine the data and
arrange the observations in order of size from smallest to largest.  Assign
the ranks (1,2,3, ... 20) to the ordered observations (1 to the smallest, 2
to the next smallest, etc.).  If ties occur in the ranking, assign the average
rank to the observation.

4.  An example of assigning ranks to the combined data for the control and
concentration IX effluent is given in Table 0.1 below.  This ranking procedure
is repeated for each control and concentration combination.  The complete set
of rankings is listed in Table 0.2.  The ranks are then summed for each
effluent concentration, as shown in Table 0.3.

5.  For this set of data, we wish to determine if the reproduction in any of
the effluent concentrations is significantly lower than the reproduction by
the control organisms.  If this occurs, the rank sum at that concentration
would be significantly lower than the rank sum of the control.  Thus, we are
only concerned with comparing the rank sums for the reproduction of each of
the various effluent concentrations with some "minimum" or critical rank sum,
at or below which the reproduction would be considered to be significantly
lower than the control.  At a probability level of 0.05, the minimum rank sum
in a test with four concentrations and 10 replicates per concentration, is 76
(see Table 0.4).

6.  None of the rank sums in Table 0.3 is less than or equal to 76.
Therefore, none of the four effluent concentrations reduced reproduction
significantly below that of the controls, and the NOEC is assumed to be 12%
effluent..
^Prepared by John Menkedick and Florence Kessler, Computer Sciences
Corporation, 26 W. St. Clair St., Cincinnati, Ohio 45268; Phone 513-568-7968)

                                       132

-------
     TABU 0.1. EXAMPLE OF STEEL'S MANY-ONE RANK TEST: ASSIGNING
              RANKS TO THE CONTROL AND IX EFFLUENT CONCENTRATION
Rank Number of Young
Produced
1
2
3
4
5
6.
6.
8
' 9
11
11
11
14
14
14
16
17
18
19
20
0
6
3
11
15
.5 16
.5 16
18
21 - .
22 .
22
22
23
23
23
24
25
26
27
31 '
Control or X Effluent
Control
IX
Control
IX
Control
Control
Control
IX
IX
IX
Control
IX
IX
-. • ' 1*
Control
Control
Control
Control
IX
TABLE 0.2.
Replicate Control
(Organism)
A
8
C
0
E
F
G
H
I
J
22 (11,11.5,13.5,13)
18 (8,6.5,8,9,)
27 (19,20,20,20)
16 (6.5,4.5,6,5)
16 (6.5,4.5,6,5)
0 (1,1,1,1)
8 (3,2,3,2)
25 (17,17,17,16.5)
24 (16,14.5,16,14)
26 (18*19,18.5,19)
22
15
21
6
23
31
23
11
23
22
TABLE
OF RANKS
Effluent Concentration
1%
(11)
(5)
(9)
(2)
(14)
(20)
(14)
(4)
(14)
(11)
3% 5&
25
25
20
24
15
23
21
22
20
18
(17)
(17)
(8.5)
(14.5)
(3)
(13)
(10)
(11.5)
(8.5)
(6.5)
23
16
7
13
26
22
21
21
21
21
(15)
(6)
(2)
(4)
(18.
(13.
(10.
(10.
(10.
(10.




5)
5)
5)
5)
5)
5)
12%
20
21
17
13
25
25
16
25
18
18

(ID
(12)
(7)
(3)
(16.
(16.
(5)
(16.
(9)
(9)





5)
5)

5)


Control ranks are given in the order of the concentration with which they
 were ranked.

                                       133

-------
                       TABLE  0.3.  RANK  SUMS
              Effluent
           Concentration
                (X).
Rank Sum
                  1
                  3
                  6
                 12
  104.0
  109.5
  101.0
  105.5
TABLE 0.4. SIGNIFICANT VALUES OF RANK SUMS: JOINT CONFIDENCE
           COEFFICIENTS OF 0.95 (UPPER) and 0.99 (LOWER) FOR
           ONE-SIDED ALTERNATIVES

*
• ' 4
5

. 6

7

3

9

10

11

12

13

14

13

IS

.-.•••33' •

18

10

20


2
11
IS
f «
id
27
23
'37
32
49
43
03
50
79
71
97
37
110
105'
138
125
161
147
-ISO
170
213
193
241
223
272
252
304
282
339
315
ft -
3
10
17

26
22
30
31
43
42
02
53
77
69
95
35
114
103
133
123
•153-
144
182
167
209
192
237
219
267
243
299
278
333
310
number of treatmtnts (excluding control)
4
10
17

25
21
35
30
47 '
41
01
54
76
63
93
34
112
102
133
121
155
142
180
165
203
190
234
217
234
245
298
275
330
307
5
10
1G

25
21
: 35
30
46
40
60,.
53-
75
97
92
83
111
100
132
120
154
141
178
1G4
204
183
232
215
262
243
294
273
327
305
6
10
•- 10
-
24
_
34
29
46
40
. 59
52
74
66
91
32
110
99-
130
119
153
140
177
162
203
187
231
213
260
241
292
271
325
303
7
-
IS

24
—
34 .
29
45
40
59
52
74 "
68
90
31
109
99
129
118
152
139
178
161
201
186
229
212
259
240
2SO
270
323
301
3
—
16

24
—
33
29
45 .
39
58
51
73
65 •
90
81
103
98
129
117
151
133
175
160
200
185
228
211 .
257
239
288
268
322
300
9
—
15

23
—
33
29
44
39
53 .
51
72
65
39
80
103
98
123
117
150
137
174
160
199
184
227
210
250
233
287
2C7
320'
299
     From Steel, 1959.
                             134

-------
                                APPENDIX  E

                            FISHER'S EXACT TEST^

1.  Fisher's Exact Test (Finney, 1948; Pearson and Hartley, 1962) is a
statistical method based on the hypergeometric probability distribution
that can be used to test if the proportion of successes is the same in
two Bernoulli (binomial) populations.  When used with the Ceriodaphnia
data, it provides a conservative test of the equality of any two survival
proportions assuming only the independence of responses from a Bernoulli
population.

2.  The data for this example (Table E.I) are mortality data from the
Ceriodaphnia survival and reproduction test, discussed in Section 13 of
this manual.

3.  For each control and effluent concentration construct a 2x2
contingency table as follows:
                                  Number of               Number of
                                                         Observations
                            Successes     Failures

             Condition 1        a           A - a             A

             Condition 2        b           B - b             B


             Total            a + b    [(A+B) - a - b]      A * B
4.  Arrange the table so that A >. B.  Categorize a success such that
a/A £ b/B.  For this data, a success may be  'alive' or  'dead1 whichever
causes a/A >. b/B.  The test is then conducted by looking up a value in
the table of significance levels of b and comparing it to the b value
given in tht contingency table.  The table of significance levels of b is
included in this example, Table E.4.  Enter Table E.4 in the section
for A, subsection for 8, and the line for a.  If the b value of the
contingency taole is equal to or less than the integer in the column
headed 0.05, a/A is significantly greater than b/B.  A dash or absence of
entry in Table E.4 indicates that no contingency table in that class is
significant*.

5.  For the control and effluent concentration of IS the appropriate
contingency table for the test is given in Table E.2.


^Prepared by John Menkedick and Florence Kessler, Computer Sciences
Corporation, 26 W. St. Clair St., Cincinnati, Ohio 45268; Phone
513-568-7968.

                                     135

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                 TABLE E.I.  EXAMPLE OF FISHER'S EXACT TEST:
                             CERIOOAPHNIA MORTALITY DATA
Effluent
Concentration (%)

Control
1
3
6
• 12
25
No. Dead

1
0
0
0
0
10
Total*

9
10
10
10
10
10
''Total number of live adults at the beginning of the test.
         TABLE E.2.  2X2 CONTINGENCY TABLE FOR CONTROL AND 1% EFFLUENT



1% Effluent
Control
Total -
Number-
A 1 Ti/a
A nve
10
3
18
of ...

ueaa
0
1
1
Number of
Observations

10
9.
19
6.  Since 10/10 218/9, the category 'alive1 is regarded as a success.
For A = 10, B * 9 and, a = 10, under the column headed 0.05, the value
from Table E.4 is b * 5.  Since the value of b (b = 8) from the
contingency table (Table E.2), is greater than the value of b (b = 5)
from Table E.4, the test concludes that the proportion of survival is not
significantly different for the control and 1% effluent.
                                    136

-------
7.  The contingency tables for the combinations of control and effluent
concentrations of 3%, 6S, 12% are identical to Table £.2.  The conclusion
of no significant difference in the proportion of survival for the
control and the level of effluent would also remain the sane.

8.  For the combination of control and 25% effluent, the contingency
table would be constructed as Table E.3.  The category 'dead' is regarded
as a succes's, since 10/10 > 1/9.  The b value (b * 1) from the
contingency table (Table E.3) is less than the b value (b » 5) from the
table of significance levels of b (Table E.4).  Thus, the percent
mortality for 25% effluent is significantly greater than the percent
mortality for the control.
          Table E.3.  2X2 CONTINGENCY TABLE FOR CONTROL AND 258 EFFLUENT
                                   Number- of	•          Number of
                                                         Observations
                               Dead .•       Alive •

            25J6 Effluent        10   "-        0              10

             Control             1            8               9


             Total              11            8           '19
                                    137

-------
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