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AR226-2810 TRADE SECRET Study Title H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricomutum AUTHORS: BarbraD. Ferrell, B.S. Robert A. Hoke, Ph.D. STUDY COMPLETED ON: May 20,2003 PERFORMING LABORATORY: E.I. du Pont de Nemours and Company Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 WORK REQUEST NUMBER: ^^^^^B^lM^ STUDY CODE NLMBER:B^B& Qompany sanitize<!- ^ s nof contain TSCA CB Page 1 of 20 H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricomutum DuPont-12989 CERTIFICATION I, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. Work Completed by: /D/U^W.. A >Ui^M^ BarbraD.Farcll.B.S. Associate Scientist Issued by Study Director; x^L/^ ^ Robert A. HokeWi.D. Senior Research Ecotoxicologist and Manager ^>Ml^2^?^ Dale t2o /^.y cJgo3 Sate ompany Sanitized. Does notcontafn TSCA C8I -2- H-24750: Influence oh Growth and Growth Rate of the Green Alga Selenastrum capricomutum STUDY INFORMATION 9th Collective Nomenclature: Synonyms/Codes: T. H-24750 Submitter's Notebook Numberfs Haskell Number: 24750 CAS Registry Number: DuPont-12989 Known Impurities:! Physical Characteristics: White Solid Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. Sponsor: E.I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: April 15, 2003 / (see report cover page) Company Sanitized. Does not contain TSCA CBB 3- H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricornutum DuPont-12989 SUMMARY A study was conducted to determine the effect of H-24750 on the growth and growth rate of the green alga Selenastrum capricornutum^ The algae were exposed to nominal concentrations of 0.1, 1, 10, 100, and 1000 mg H-24750/Liter of nutrient medium (ppm). The algae were exposed for 72 hours (3 days) without test medium renewal. The effect was expressed as percent inhibition in growth based on healthy cell count (also referred to as cell density) relative to the blank (culture medium) control for the 72-hour (day 3) interval of the test. The 72-hour EC5o, including the 95% confidence intervals (C.I.),13based on nominal concentrations are as follows:0 Healthy Cell Count EC5o NOEC 10.6 mg/L (95% C.I. = 5.8 to 15.5) 1 mg/L H-24750 exhibited medium concern'1 under TSCA and was classified as "harmful" to aquatic organisms (R52)e under the EU Directive in a 72-hour, acute test using the green alga Selenastrum capricornutum. a Also known as Pseudokirchneriella subcapitata. b The EC5o is defined as the "effective concentration" producing a 50% inhibition of growth relative to the control. c Slob, W., (2002). Dose-response modeling of continuous endpoints. Toxicological Science, V66; pp 298-312. d Smrchek, J., Clements, R., Morcock, R., and Rabert, W. (1993). Assessing ecological hazard under TSCA: methods and evaluation of data. Environmental Toxicology and Risk Assessment, ASTMSTP 1179. (W.G. Landis, J.S. Hughes, and M.A. Lewis, Eds.), pp 22-39. American Society for Testing and Materials, Philadelphia. e Official Journal of the European Communities, Volume 36, 4 May 1993, pp. 68, section 5.2.1. -4- Company Sanitized. Does not contain TSCACBI H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastmm capricornutum DuPont-12989 MATERIALS AND METHODS A. Test System Selenastmm capricornutum, a freshwater, unicellular, non-motile, green alga, was used in this study. The original culture source was the Department of Botany - Culture Collection of Algae The University of Texas at Austin - Austin, Texas 78713-7640. The culture method for Selenastrum capricornutum was based on published literature.0'21 Prior to the study, Selenastrum capricornutum cultures were maintained under the same environmental conditions used in the study. The organisms were cultured in sterilized 250 mL Erienmeyer flasks containing approximately 50 mL of filtered (= filter-sterilized) synthetic algal-assay procedure (AAP) nutrient medium and were aseptically transferred to fresh medium every 3 to 7 days. The flasks were fitted with foam stoppers to permit gas exchange. B. Test Design The test design used for the Selenastrum capricornutum study is described below: Nutrient Flask Volume Solution Volume Volume Organism___________Medium____(mL)_______(mL)_____Ratio Selenastrum capricornutum AAP 250 50 5:1 C. AAP Nutrient Medium Preparation for Selenastrum capricornutum (Appendix A) AAP nutrient medium0) was prepared by adding 1 mL of each of the 6 macronutrient stock solutions and 1 mL of the micronutrient stock solution to approximately 800 mL ofMilli-Q (deionized) water, with mixing after each addition. The volume of the medium was brought to 1 liter with additional Milli-Q water. Appropriate proportions (1 mL of each stock solution for each 1 liter of medium) were used to prepare the larger volumes of the medium required for the study. The medium pH was adjusted to approximately 7.5. The medium was filter-sterilized using Corningpre-sterilized filtration systems each with a 0.22 pm cellulose acetate filter. 1. Test Solution Preparation Five nominal test concentrations (0.1, 1, 10, 100, and 1000 mg H-24750/L AAP nutrient medium) were used in this study. Aliquots of the filter-sterilized AAP nutrient medium were used for the blank (normal culture medium) control solution. -5- ompany Sanitized. Does not contain TSCA CBfl 9> H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricornutum DuPont-12989 2. Test Culture Preparation For each blank control and test solution, 2 aliquots (50 mL each) were placed in separate sterilized 250 mL Erienmeyer flasks fitted with sterilized foam stoppers. To achieve the desired nominal concentration of approximately 10,000 Selenastrum capricornutum cells/mL at test initiation, an approximate 0.475 mL (= 475 uL) aliquot of algal inoculum from a logarithmically growing stock culture was aseptically transferred to each flask. D. Experimental Design and Test Conditions The test flasks were placed on a shaker table in an environmental chamber in a non-systematic design and were re-positioned each working day. Air temperature in the chamber was recorded continuously with a continuous temperature recorder. Each blank control and test concentration was tested as 2 replicates. The algae were incubated without test medium renewal and cell counts were made after 72 hours. Illumination was supplied by cool-white fluorescent tubes. The target environmental parameters are described in the following table. Initial Illumination ___Population____(lumens/m2 = lux) 10,000 cells/mL 6000 to 10.000 PhotoPeriod (hours) 24 Shaking Speed Temperature (rpms)____(C) 100 24 2 E. Selenastrum capricornutum Growth Measurement Selenastrum capricornutum growth measurement was determined by visually counting the number of cells taken from an approximate 0.2 mL sample from each flask at approximately 72 hours from study initiation. The counts were conducted using a hemacytometer and a compound microscope. An aliquot of each sample was loaded into each side of the hemacytometer and 8 grids from each side were selected for counting. All cells located in the 16 grids were counted and recorded as healthy or unhealthy. The total number of cells counted was multiplied by 10,000 to determine the number of cells per milliliter. Observations and counts of healthy and unhealthy cells (e.g., deformed, scenescent, stunted) were recorded in the study records. The statistical calculation of the EC5o was based on mean healthy cell counts and nominal test substance concentrations. Companyganillzea. Does not contain TSCA CBl 6- H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricornutum DuPont-12989 RESULTS Based on visual observations, the blank control solution and the 0.1, 1, 10, and 100 mg/L test solutions were clear and had no color before addition of algal cells. The 1000 mg/L test solution was clear and had undissolved particles of test material and a surface film. After the addition of algal cells, the test and blank control flasks were placed on a shaker table in a chamber with a temperature of approximately 25C. The algae were incubated for 72 hours without medium renewal. Illumination was supplied by cool-white fluorescent tubes. The mean light intensity in the chamber was 7564 lumens/m2 (= lux). The shaking speed was 96 revolutions per minute (rpm). The pH measurement of the culture medium was approximately 7.5 at study start. The pH measurements of the test solutions at test initiation ranged from 3.20 to 7.47, and at test termination ranged from 3.33 to 7.86. CONCLUSIONS The 72-hour EC^o, including the 95% confidence intervals (C.I.)3 based on nominal test substance concentrations and the NOEC are as follows:^5 Healthy Cell Count EC5o NOEC 10.6 mg/L (95% C.L = 5.8 to 15.5) 1 mg/L H-24750 exhibited medium concern (4) under TSCA and was classified as "harmful" to aquatic organisms (R52/5^under the EU Directive in a 72-hour, acute test using the green alga Selenastrum capricornutum. Company Sanitized. Does not contain TSCA CBS a The EC5o is defined as the "effective concentration" producing a 50% inhibition of growth relative to the control. -7- H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricornutum_____________________________DuPont-12989 REFERENCES 1. Miller, W.E.; Greene, J.C.; Shiroyama, T. The Selenastrum capricornutum Printz Algal Assay Bottle Test; U.S. Environmental Protection Agency; U.S. Government Printing Office: Washington, DC, 1978; EPA-600/9-78-018. 2. American Society for Testing and Materials (ASTM). (1990). "Standard Guide for Conducting Static 96-h Toxicity Tests with Microalgae" in ASTM Annual Book of Standards, E1218-90. Vol. 11.04, Philadelphia, PA. 3. Slob, W., (2002). Dose-response modeling of continuous endpoints. Toxicological Science, V66;pp 298-312. 4. Smrchek, J., Clements, R., Morcock, R., and Rabert, W. (1993). Assessing ecological hazard under TSCA: methods and evaluation of data. Environmental Toxicology and Risk Assessment, ASTMSTP 1179. (W.G. Landis, J.S. Hughes, and M.A. Lewis, Eds.), pp 22-39. American Society for Testing and Materials, Philadelphia. 5. Official Journal of the European Communities, Volume 36, 4 May 1993, pp. 68, section 5.2.1. ^^"'^''"."o.eon^^M 8- H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricornutum DuPont-12989 TABLES ^ C-6wnnv S^W^-d. Does not contain TSCA CBI 9- H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricornutum DuPont-12989 TABLE 1 pH MEASUREMENTS OF TEST SOLUTIONS Nominal Concentration Test Initiation (0 hours) Test Termination (72 hours) (mg/L)__________pH______________pH____ Blank Control 7.41 7.74 0.1 1 10 100 1000 7.47 7.42 7.33 6.33 3.20 7.78 7.84 7.86 6.99 3.33 Company Sanitized. Does not contain TSCACB8 10- H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricornutum DuPont-12989 TABLE 2 DATA SUMMARY Nominal Day 0 Healthy Cell Count Day 3 Healthy Cell Count Concentration______(cells/mL)__________(cells/mL) Blank Control Replicate 1 Replicate 2 10,000 10,000 3,140,000 2,580,000 0.1 mg/L Replicate 1 Replicate 2 10,000 10,000 3,080,000 3,420,000 1 mg/L Replicate 1 Replicate 2 10,000 10,000 2,540,000 2,600,000 10 mg/L Replicate 1 Replicate 2 10,000 10,000 1,460,000 1,760,000 100 mg/L Replicate 1 Replicate 2 10,000 10,000 10,000 0 1000 mg/L Replicate 1 10,000 0 Replicate 2 10,000 0 Company Sanitized. Does not contain TSCA CBl 11- H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastmrn capricornutum DuPont-12989 FIGURE Company Sanitized. Do,e^ not contain TSCA CBl 12- H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastmm capricornutum DuPont-12989 FIGURE 1 72-HOUR HEALTHY CELL COUNT DOSE-RESPONSE CURVE or nulnl 400: tc 300- OECO Model 2, Using MARQUARDT Method rORUUKI r011 HOrE.tB14339SC115 fOUUI.AI=CtlI.Conl;2 / 10000 COMCENIBAIIDHS=0 O.I I 10 100 1000 ZOO- 100- I B- 50 pet iitiintion -100- i ' ' i ' i ' i i < i ' ' ' i ' i i i i ' ' ' i i ' ' i ' r ' ' ' ' 1 ' ' i ' ' ' i ' ' ' ' i ' ' ' ' r 1DO 200 300 400 50D SOO 700 BOO 900 1000 110 CDNC OECO Model 2. Using MARQUARDT Melhod rORUULAI FBOM HOU.AWB14.139SC.115 FOBHULAI.CEII.CoBtm / 10000 COHCCHTIiAIIOIIS^O O.I I 10 100 1000 COHC -13- ComBany Sanitized. Does not contain TSCA CB1 H-24750: Influence brfGrowth and Growth Rate of the Green Alga Selenastnim capricomutum DuPont-12989 APPENDICES Company Sanitized. Does not contain TSCACBl 14- H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricornutum DiiPont-12989 APPENDIX A AAP Nutrient Medium Constituents Company Sanitized. Does not contain TSCACBl 15- H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricornutum DuPont-12989 AAP NUTRIENT MEDIUM CONSTITUENTS Stock Solutions3 Component_____Concentration (g/L) Macronutrient Stock #1 NaN03 25.500 Macronutrient Stock #2 NaHCOs 15.000 Macronutrient Stock #3 K2HP04 1.044 Macronutrient Stock #4 MgS04-7H20 14.700 Macronutrient Stock #5 MgCl2-6H20 12.164 Macronutrient Stock #6 CaCl2-2H20 4.410 Final Prepared Medium Component Concentration (mg/L) Na 11.001 N 4.200 C 2.143 K 0.469 P 0.186 Mg 2.904" Ca 1.202 S 1.911 Stock Solutions' Component Concentration (mg/L) Micronutrient Stock H3B03 MnCl2-4 H20 ZnCl2 CoCl2-6 H20 CuCl2-2H20 Na2Mo04'2 H20 FeCl3-6 H20 Na2EDTA-2 H20 185.520 415.610 3.271 1.428 0.012 7.260 160.000 300.000 Final Prepared Medium Component Concentration (ug/L) B 32.460 Mn 115.374 Zn 1.570 Co 0.354 Cu 0.004 Mo 2.878 Fe 33.051 a As reported in Reference 2. b Includes magnesium from both magnesium sulfate and magnesium chloride. -16- Company Sanitized. Does not contain TSCA CBl H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricornutum DuPont-12989 APPENDIX B 72-Hour Healthy Cell Count Statistics Company Sanitized. Does not contain TSCACBI 17- H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricomutum DuPont-12989 72-HOUR HEALTHY CELL COUNT STATISTICS MOEC Determination Using StatXact !K Independent Samples:Jonckhere-Terpstra Test > KI JT/EX /RO=CONC /CO=COUNT72 All concentrations present Datafile: C: \AQUA7XCS\hoke^^--------------fctxdata.cy3 JONCKHEERE-TERPSTRA TEST [That the 6 populations are identically distributed] Statistic based on the 12 observations: Mean 30.00 Std-dev 7.129 Observed(JT(x)) 5.000 Standardized(JT*(x)) -3.507 Asymptotic p-value: One-sided: Pr ( JT*(X) .LE. Two-sided: 2 * One-sided -3.507 } = = 0.0002 0.0005 Exact p-values: One-sided: Pr { JT*(X) -LE. Pr { JT*(X) -EQ. Two-sided: Pr { |JT*(X)| .GE. -3.507 } = -3.507 } = 3.507 } = 0.0001 0.0000 0.0001 !K Independent Samples:Jonckhere-Terpstra Test > KI JT/EX /RO=CONC /CO=COUNT72 1000 mg/L omitted Datafile: C: \AQUATICS\hokeBBBBBBBtxdata. cy3 JONCKHEERE-TERPSTRA TEST [That the 5 populations are identically distributed] Statistic based on the 10 observations: Mean 20.00 Std-dev 5.477 ObservedfJT(x)) 4.000 Standardized(JT*(x)) -2.921 Asymptotic p-value: One-sided: Pr { JT*(X) .LE. Two-sided: 2 * One-sided -2.921 } = = 0.0017 0.0035 Exact p-values: One-sided: Pr { JT*(X) -LE. Pr { JT*(X) .EQ. Two-sided: Pr { |JT*(X)| .GE. -2.921 } = -2.921 } = 2.921 } = 0.0012 0.0007 0.0024 !K Independent Samples:Jonckhere-Terpstra Test > KI JT/EX /RO=CONC /CO=COUNT72 1000 and 100 mg/L omitted Datafile: C: \AQUATICS\hokeM--------|--------Ltxcdya3ta. Company Sanitized. Does not contain TSCA CBi 18- H-24750: Influence on_Growth and Growth Rate of the Green Alga Selenastnim capricomufum DuPont-12989 JONCKHEERE-TERPSTRA TEST [That the 4 populations are identically distributed] Statistic based on the 8 observations: Mean 12.00 Std-dev 3.916 Observed(JT(x)) 4.000 Standardized(JT*(x)) -2.043 Asymptotic p-value: One-sided: Pr { JT*(X) -LE. Two-sided: 2 * One-sided .043 } = 0 .0205 0 .0411 Exact p-values: One-sided: Pr { JT*(X) ,LE. Pr { JT*(X) .EQ. Two-sided: Pr { |JT*(X)| .GE. -2.043 } = -2.043 } = 2.043 } = 0.0262 0.0139 0.0524 !K Independent Samples:Jonckhere-Terpstra Test > KI JT/EX /RO=CONC /CO=COUMT72 1000, 100, and 10 mg/L omitted Datafile: C:\AQUATICS\hoke stxdata.cy3 JONCKHEERE-TERPSTRA TEST [That the 3 populations are identically distributed] Statistic based on the 6 observations: Mean 6.000 Std-dev 2.517 Observed(JT(x)) 4.000 Standardized(JT*(x)) -0.7947 Asymptotic p-value: One-sided: Pr { JT*(X) .LE. Two-sided: 2 * One-sided -0.7947 } = = 0.2134 0.4268 Exact p-values: One-sided: Pr { JT*(X) .LE. Pr { JT*(X) .EQ. Two-sided: Pr { |JT*(X)| .GE. -0.7947 } = -0.7947 } = 0.7947 } = 0.2889 0.1222 0.5778 Comoany Sanitized. Does not contain TSCA CB1 19- H-24750: Influence on Growth and Growth Rate of the Green Alga Selenastrum capricomutum DuPont-12989 EC50 Estimation Using OECD Model 2 OBSERVED & PREDICTED PERCENT CHANGEFROMCONTROL MEAN FORMULAl FROM HOK^BIHB--------A FORMULAl =Ce 1 l_Count72/nffu<^^ Obs CONC N MEAN PRED PCTCHNG PREDPCTCHNG 1 0.0 2 286.0 297.537 2 0.1 2 325.0 295.603 3 1.0 2 257.0 278.759 4 10.0 2 161.0 155.034 5 100.0 2 0.5 0.439 6 1000.0 2 0.0 0.000 0 14 -10 -44 -100 -100 0 -1 -6 -48 -100 -100 EC50 using Method=MARQUARDT, OECD Model 2 Covariance Matrix and Standard Error of Parameter Estimates _NAME_ yO EC50 SE EC50 yO -8.778 102.717 6.06778 -8.77808 2.4633 10.1350 Model 2 Parameter Estimates, EC50 and 95% Confidence Bounds yO EC50 LB UB 297.537 10.6328 5.80478 15.4609 SSREG Model 2 Evaluation Measures SSERR SSTOTC SSTOTU 521335.79 5301.12 21827.68 526636.92 note Graph descriptions include the following: formulal: EC50 OECD MODEL 2 FIT BY MARQUARDT, RSQUARE .0.75714 cwvwvsm1^^^ 20-