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. ov. ARL2S -00%5 PFOS: `A 96-HOUR TOXICITY TEST WITH THE "FRESHWATER ALGA (Selenastrum capricornutum) FINAL REPORT `WILDLIFE INTERNATIONAL LTD. PROJECT NUMBER: 454A-103A 3M LABREQUESTNO. U2723 nd U.S. Environmental Protection Agency Series - 850O-PEPcTolSogNiucamlbEefrfe8c5t0s.T5e4s0t0Guidelines (OECD Guideline 201 AUTHORS: Kurt R. Drotar Henry O. Krueger, Ph.D. STUDY INITIATION DATE: December 4, 1998 STUDY COMPLETION DATE: June 4, 1999 AMENDED REPORT DATE: April 26, 2000 Submitted to Envir3oMnmCeonrtp]orLaatbioornatory 935 Bush Avenue St. Paul, Minnesota 55144 Wildlife I45n98tCoemrmenrcae Dtriiveonal Ltd. Easton, Vargiand 21601 (410) 822-8600 Page 1 of 58 0 00607 AMENDED WILDLIFE INTERNATIONAL Lm. 2. PROJECT NO.: 454A-103A GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT SPONSOR: 3M Corporation TITLE: PFOS: A 96-Hour Toxicity Test with the Freshwater Alga (Selenastrum capricormutum) WILDLIFE INTERNATIONAL LTD. PROJECT NUMBER: 454A-103A STUDY COMPLETION: June 4, 1999 REPORT AMENDED: April 26, 2000 Thisstudy wasconductedincompliancewith GoodLaboratoryPracticeStandardsaspublished by tPhreincUiSpSl.esoEnfvGirooondmeLnatbaolraPtroorteycPtriaocntiAcge,enOcCyDiEn/4G0DC(9F2R) 3P2a,rtEsnv1i6r0onamnednt M79o2n,og1r7apAhugNuos.t451,98P9a;risOE19C9D2 and Japan MAFF, 59 NohSan, Notification No. 3850, Agricultural Production Bureau, 10 August 1984 with the following exceptions: characteTrihzaettieosntwsaubssptearnfcoerwmeadsanccootrcdhianragcttoer3iMzedSitnaandcacrodrdOapnecraetwiintghPfruolcledGuLrePscaonmdplMieatnhcoed;sh,oawnedvaelrl,rtahs e dataarebeingmaintainedinthe 3Marchives.Thetestsubstance isbeingrecharacitneacrcoirdzaencde with GLP accordTanhceestwaibtihliGtyooofdLtahbeotreasttosruybsPrtaacntciecuenSdtearncdoanrddsi.tionsofstorageatthYetes steWasnotdeterminedin ul STUDYDIRECTOR: Kurt R_Drotaar DATE Seaior Biologist SPONSOR: 4. Ra f AMENDED 000608 WILDLIFE INTERNATIONAL Lm. 5. PROJECT NO.: 454A-103A `QUALITY ASSURANCE STATEMENT `Thisstudywas examinedforcompliancewithGoodLaboratory PracticeStandardsaspublishedby the U.S. Environmental Protection Agency in 40 CFR Parts 160 and 792, 17 August 1989; OECD PrinciplesofGood Laboratory Practice, OCDE/GD (92) 32,Environment Monograph No. 45, Paris 1992; and Japan MAFF, 59 NohSan,Notification No. 3850, Agricultural Production Bureau, 10 August 1984. "Thedatesof allinspectionsandaudits andthedates thatanyfindingswerereported tothe StudyDirector `andLaboratoryManagementwereas follows: sce DATECONDUCTED: STUDYDIRDEACTTOER.REPORMTAENDATGOEMENT: i oaion InitialTrial 454A-103 Fey 18,99 Fay18.199 Fehr 19,199 - nS FrayRud, 1999 Fay 1999 Februay24, 199 DutRepotasdDes Mash 9,159 Meh15,199 Marh30,1999 DnfRemiDe DTesetSufbsitTarnnicaeliPr4et5p4airAa-tv1i0one3A fAinalytimcail Data and Four AmendedRegn Apil 9, 1999 MaylomdlL1% Moy Omi Je, 199 AS00 April9, 1999 Mayll, 9 May, 19 3 Sot, 199 ARR0 oy Apil 12,1999 Moy. Je,1999 A200 iLy Timothy A' Springer, Ph.D. `Manager, Regulatory and Technical Support Satfoo DATE AMENDED 000609 WILDLIFE INTERNATIONAL Lm. 4 PROJECTNO.: 454A-103A REPORT APPROVAL SPONSOR: 3M Corporation TITLE: PFOS: A 96-Hour Toxicity Test with the Freshwater Alga (Selenastrum capricornutum) `WILDLIFE INTERNATIONAL LTD. PROJECT NUMBER: 454A-103A STUDY DIRECTOR: as, \ Kurt R_ Drotar Senior Biologist : Sf36/08 DATE MANAGEMENT: Henry 6. PhD. Director,Aquatic Toxicology `and Non-Target Plants 5/50Jee DA AMENDED 000610 WILDLIFE INTERNATIONAL Lo. $e "TABLE OF CONTENTS PROJECTNO: 454A-103A TIS ACE msmmpmmmmmnsesmmmmmmms---------- LE : TABLES : Table 1 - SummaryofAnalyticalChemistryData ............. - 19 Tabl2e - Temperature Measuremeas ........... tts 20 Tabl3e - LightIfensityMeASuICmENts.......vovovevenevsrsoneevnen 21 BE -- nll Tabl5e - Pg MeanCellDensitiesand PercentInhibitionforEach Tabl6e - M2e4a-HnoAUrreIansrUVnadleDrUtFhIeOGGrtohwetThECSurvear ndPerr cent r InhibitionforEach 28 Table 7- MeanGrowthRatesandPercentInhibitionforEach24-Hour Interval AMENDED 000611 WILDLIFE INTERNATIONAL Lm. "6- PROJECT NO.: 454A-103A TA OFB COL NTEE NTS ~Continued- Tabl8e-EEXCP1O0S,UTEEC5P0IaOnd.E.C.90ValuesBasedonCellDensityOverthe96-HourS--. Tabl9e- EtChe1096,-EHoCu5r0EaxnpdosEuCre90PVearliuoeds.B.a.sedonArea UndernthemGromwthmCurmveO--ver------ `Table 10- EC10,EC50and EC90 ValuesBased on GrowthRateOverthe 96-Hour "Table 11 -Cell DensitiesfortheReCOVEryPHASE .............c.ccovrvsvvnsriurrsssssssmsssnsessssssnsssssesss 29. FIGURES Figu1r-e NegativeControlAlgalGrowth,Expressed inCellDensity, Duringthe96-HourExposue....... men 30 Figure 2- Concentration-ResponseCurve,ExpressedinCellDensity. Figu3re- RecoveryPhase ResponseCurve, ExpressedinCell DENSI 31 ............oerrinncc: 32 APPENDICES Appendix I~ Analyses of Pesticides,Organics, MetalsandOtherInorganics in WildlifeInternationalLtd.Well Water................... ermine: 38 Appendix II-I TheAnalysisofPFOS inFreshwaterAlgalMediumin Supporoft `WildlifeInternationalLtd. Project No.: 454A-103A........occcovve --J Appendix IV- CellDensityforEachReplicate Per TreatmentOver the 96-HourExposurePeriod.......... tt ---------- Appendix V- AreaUndertheGrowthCurvefor EachReplicate Per TreatmentOverthe 96-HOUTEXPOSUTEPEriO.....rv rr ttre 53 AppendixVI - GrowthRateforEachReplicatePer TreatmentOverthe 96-HourExposurePeriod.54 APEXVIL+ CHA80DPIOGIOGEOL S rms 55 AppendixVIII - PersonnelInvolvedinthe Study. te sna 36. APPERix TX = REPORtAMEIMEDE css ST AMENDED 000612 WILDLIFENINETERRNNAATOIONNAALLtLom.. 7. PPRROOJJEECCTTNNOO.. 445544AA-l10033AA Ey `SPONSOR'S REPRESENTATIVE: DLAOTCAATAINODN OAFCOSPTUYDYO,FTRHAEW FINAL REPORT. WLTIDL,DLPIRFOEJIENCTTENRUNMABTEIRO:NAL TEST SUBSTANCE: STUDY: MCEOANCNEMNETARASTUIROENDST:EST TEST DATES: LENGTHOFEXPOSURE: TEST ORGANISM. SOORUGRACNEISOMFST:EST C7E2L-LHODUER ETCSY0: 95%CONFIDENCE LIMITS: 9956%:HCOOUNRFIECDIE0N:CELIMITS: 9956%:1COOUNRFIECDSE0N:CELIMITS: 9965:%HOCUORNFEICDOE0N:CE LIMITS: 72-HOURNOAEC: 96-HOUR NOAEC SUMMARY M Corporation Ms. Susan A. Beach 'EWaisltdoinf,eMInDtern2a1ti6o0n1al Ltd. 454A-103A PFOS (Perfluoroocatane SulAfcidoPontasisicum Salt) P(SFeOlSe:nasAtr9u6m-cHaopurricTooxrincuittuym)Test with the Freshwater Alga NegContarol,t5.5i,11,v21,e44, 86and 179mg aL EExxpepriomsentTaleSrtamrti- nAApripl 1a2, 1169,919999 . Experimental Termination-April 21, 1999 96Hours . cshvwater Alga (Selenastrumcapricormam Wildsitofn,eIntemaMatrylianodn2al16L0td1. ~, 4740amngd a7i8lm,gai/L, 4439amngdaSiOlmgai/L 761m6g .7a3imalgna.id/L 110357amngda1i5/3lmgai /L 44mgaill A4mgaill, AMENDED 000613 WILDLIFE INTERNATIONAL Lo. -s- PROJECT NO.: 454A-103A C"AURREVAEUNDER THEE GROWTH 9T52%HOCUONRFEICDSE0N:CELIMITS: 96-HOUREC10: 195%CONFIDENCELIMITS: 9965-%HCOOUNRFEICDSE0N:CELIMITS: 96-HOURECS0: 95% CONFIDENCELIMITS: T2-HOURNOAEC: 96-HOUR NOAEC: SUMMARY (Continued) 5754.mangda8i2 mgai/L 49mgai/l 40and 50mg ai/L 67Im7gaTiaalmlngaidl 145 mgaill 125and 155 mgai/L H4mgaill 44 mgaill "GROWTHRATE 72-HOURECS0: 95%CONFIDENCELIMITS: 120mg ill . 103and 132mgai/L 96-HOUR EC10: 59mgai/L 95%CONFIDENCELIMITS: . 54and 63 mgai/l i 9965-%HOCUORNEFCISD0E:NCELIMITS: 11261mga51i3/8almg0aid/L, 96-HOUR EC90: 95% CONFIDENCE LIMITS: >179 mgai/l. Not Calculable 72-HOUR NOAEC: 44mgaill 96-HOURNOAEC: 4amgaill AMENDED 000614 WILDLIFE INTERNATIONAL Lo. -9- PROJECT NO. 454A-103A INTRODUCTION This studywasconductedby Wildiie InternationalLtd.for 3M Corporation atthe Wildiife Intemational Lid.aquatictoxicologyfacilityinEaston,Maryland. Thein-ifephaseofthetestwas conductedfromApril 12, 1t9oA9pril921, 1999. RawdatageneratedbyWildlifeInternationalLtd and a. copyofthe finalreportare filed under Project Number 454A-103A in archives located onthe Wildife IntematiLuod.nsiatle. OBJECTIVE The objectiveofthe study was to evaluate the toxicityof PFOS (Perfluorooctane Sulfonic Acid Potassium Salt) to the growth of the freshwater alga, Selenastrum capricormutum, during a 96-hour `exposureperiod. EXPERIMENTALDESIGN The freshwater alga, Selenastrum capricormutum, was exposed to a geometric seriesofsix test concentrationsand anegative(culturemedium)control under static Conditions for 96hours. Three replicatetestchambersweremaintainedforeachtreatment andcontrolgroup. Oneadditonalreplicatewas alsomaintainedforanalyticalsamplingonDay 3ofthetest.Inaddition, one"abiotic"replicate (test solutionwithoutalgac)waspreparedforthehighesttestconcentration. Notm estcoincenn tratiaonswlere selectedinconsultation withthe Sponsorandwerebasedupontheresultsofrangefinding anddefinitive tests. Thenominaltestconcentrationsselectedwere 5.7,11,23,46,91and183mgactiveingredient (aL. Meanmeasuredtestconcentrationsweredeterminedfromsamplesoftestmediumcollectedfrom eachtreatmentandthecontrolgroupatestinitiation,atapproximately72hours,anda testtermination. Attestinitiation,aninoculumofthealgalcellswaspreparedat aconcentrationofapproximately 1.0X 10cells/mL. Theconcentrationofalgalcelsintheinoculum wasverifiedand 1.0mLvasaddedto eachtestchambertoachieve a nominalconcentration ofapproximately 1.0 X 10celisnL. Sampleswere AMENDED 000615 A WILDLIFE INTERNAA TIONAL , Lm. "10- PPRROOJTECCTTNNOO.:: 4M54AA-G103AA collectedfromeachreplicatetestchamberatapproximately 24-hourintervalsduringthetestto determine. cell densities. Celldensitieswere measuredforeachreplicateandwereusedtocalcarueaslunadetrtehe `growth curveandgrowrattehs. Percentinhibitionvalues relativetothecontrolwerecalculated forcach `parameter overthe 96-hourexposureperiod. ECSOvaluesbased upon cell densities,areas underthe growthcurveandgrowthrateswerecalculatedforeach24hourinterval. EC10and EC90valuweerse. calculated, if possible, for the 72 and 96 hour intervals. The no-observed-adverse-effect-concentration (NOAEC)wasdeterminedbaseduponstatisticalevaluationofthe 72-hourand 96-hourresults.Attheend `of the96-hourexposure,algistaticeffectsweredifferentiated fromalgicidaleffects. MATEARNDIMA ETL HOS DS "Thestudywasconductedaccordingtotheproceduresoutlinedintheprotocol,"PFOS: A96-Hour Toxicity Test with the Freshwater Alga (Selenastrum capricornutum)". The protocol was based on proceduresoutlined inthe U.S.EnvironmentalProtectionAgencySeries850-EcologicalEffects Test Guidelines, OPPTS Number 850.5400: Algal Toxicity Tiers I and II (draft)(1) and OECD Guidelines for TesoftChiemincalgs, 201 Algal, Growth Inhibition Test (2). TestSubstance : : The test substance was received from 3M Corporation on October 29, 1998 andwasassigned `WildlifeInternationalLtd.identifniucmbaetr4i6o75n.Thetestsubstancewasdescribedas a white powder. It was identified as FC-95 fromlotnumber 217 (T-6295). Information provided by the Sponsor indicated apurity of 98.9%and anexpirationdateof 2008. Thetestsubstance wasreanalybyztehde SponsorandtheCertificateofAnalysisdatedMarch9, 2000indicated apurityof90.49%. Thetest substance wasstoredat ambientroom temperature. PrepoafTerstaContcenitraotionns Nominaltestconcentrawterieo5n.7s,11, 23, 46, 91 and 183mga.i./L,basedon atest substance puorf9i0.t49y%. Allmaterials whichcameintocontactwiththe testsubstanceduringpreparationoftest `concentrationswereconstructedofplasticorstainlesssteel. Aprimary stocksolutionwaspreparedinalgal AMENDED 000616 WILODULITF:E NITNETRERNNAATTIIOONNAALLLLor.. 1. PPRROOJJEECCTTNNOO.: 445544AA--1l033AA `mediumat aconceatrationof 183mga../L.Theprimarystocksolutionwasstirredwith a magneticstir plate for approximately24 hours 10aidinthesolubilizationofthe testsubstance. Afermixing,the primarystocksolutionwasproportionally dilutedwithalgalmediumtopreparethefiveadditionaltest concentrations. Allfinalestsolutionsappearedclearandcolorless. TestOrganism "Thefreshwateralga,Selenastrumcapricornutum,wasselectedasth tetspeciesforthis study. The species isrepreseatative ofan important groupoffreshwateralgae,and was selected for useinthe test basedupon apasthistoryofuseandcaseofculturinginthe laboratory. Orialggalciultnureaswelre obtainedfromUTEX -TheCultureCollectionofAlgaeattheUniversityof TexasatAustinandhavebeen maintainedinculturemediumat WildlifeInternational L1d., Easton,Maryland.Algalcellsusedinthi test wereobtainedfromWildlifeIntemationLadl.culturesthathadbeen activelygrowinginculturemedium foratleasttwoweeksprior totestinitiation.Thenegativecontrolorganisms wereexpectedtqexhibit exponentialgrowthoverthe 96-hourexposureperiod.Exponentialgrowth,definedastheperiodofgrowth wherethealgalcellsaredividingat aconstantrate,isindicatedbythelinearsectionofthegrowthcurve (Figure1). OECDguidelinesrecommendthatcontrolcellgrowthshouldhaveincreasedby afactor ofat east 16with3diayns. CultureMedium `Thealgalcellswereculturedandtestedinfreshwateralgalmedium (3). Stocknutrientsolutions werepreparedby addingreagent-gradechemicalsto WildlifeIntemationalLtd.wellwaterpurified by reverseosmosis.Thetestmedium waspreparedbyaddingtheappropriatevolumesofstocknutrient solutionstopurifiedwellwater (AppendiIx.ThepH ofthemediumwasadjustedto7.5 +0.1using 10% HCIandthemediumwassterilizedby filtration(0.22 um) priortouse. Arweareplerfyormsedaetlesast `once annually todeterminetheconcentrationsofselected organic andinorganic constituentsinthewell water. Theresultsofanalysesperformedtomeasuretheconcentrationsofselectedcontaminantsinwell waterusedby WildifeInternationalLid. arepresentedin AppeadixII AMENDED 000617 e WILDe LIFEeINEe TERRNe ATTIIOOe NNAALLe LLImD.. eeeeee PCRIOJEEe CCTTNNOO.m :LS45A4n AM-1E03.n A S124 TestApparas Test chambersweresterile, 250-mL polycarbonate Erlenmeyer flasks plwuithgfoagmsteoppders `andcontained 100mLoftestorcontrolalgalmedium.Thetest chamberswerelabeledwiththeproject `number, concentration and replicate, and were indiscriminately positioned on a mechanical shaker table in anenvironmentalchamber designedto maintainthedesiredtesttemperature throughoutthetest.Thetest chamberswereshake continuato1u00srlpym. Environmental Conditions Test flasks wereheldinancovironmentalchamberata temperatureof24+2C.Thetemperatuorfe acontainerofwater adjacenttothetestflasksintheenvironmentalchamberwasrecordedtusicedaily duringthetestusing aliquid-in-glassthermometer. `Thealgaewereheldundercontinuouscool-white fluorescentlightingthroughoutthetest. Thetarget lightintweasn430s0 +i43t0lyux. Lightintensitywas measuredatthefour comersandthemiddleofthe shakertabledaly.Lightintensity wasmeasuredusingan SPER ScientificModel 840006lightmeter. `The pHofthemediumpreparedforeachtreatmentandcontrolgroupwasmeasuredattestinitiation andtermusiniganFishaerAtccuimetoModnel 915 pH meter. Samples forpHmeasurematetnestt initiationwerecollectedfromtheindividualbatchesoftestsolution preparedforeachtreatmentandcontrol group. Attesttermination,samplesoftestsolution werecollectedfrompooledreplicatesofthetreatment `andcontrolgroupsfor pHmeasurement. AlgalGrowthMeasurements Testmedium samples werecollectedfromthetreatmentandcontrol groupsforthedetermination of algalcelldensities. Singlesamples werecollectedfromeachofthethree"biological"replicatesper treatment andcontrolgroupat 24-hour intervalsduringthe96-hour exposure,andwere counted immediately. Cellcountswereconductedusing ahemacytometerand microscope. Eachsamplewas dilutedusinganelectrolytesolution(Isoton),asneeded,tomaintaincountingaccuracy. Asmallamount ofcachsamplewasloadedonto ahemacytometerand10gridswerecounted. Themean numobfecelrls 000618 DWN ILDLIFE INTERNATIOA NAL Lr. eee TPRROOTJEECCTTNNOO.::444548A-010038A 13. ) pergridwasestimatedandthisvaluewasusedtocalculatethecelldensity ofthesample, Usingthis technique,theminimum quantifiableclldeasitywas 1.0 X 10 cells/mL. All 96 ourcellcountsampleswereexaminedmicroscopicallyforatypicalcellmorphology(e, changesincellshape,sizeorcolor). Growthofcllin thereplicatetestchambersalsowasassessedfor `aggregationsorflocculation ofcellsandadherenceofthecelstothetestchamber. `Statistical Analyses Celdensities,areaunderthegrowthcurvevalues,growthrates andpercentinkibitionvalueswere calculatedusing "The SAS System for WindoRelweasse"6.,12 (4). Arcaunderthegrowthcurvewas calculatedforthecontrolandtreatmeatgroup usingthefollowingformula: A= (ONY2EHNAN ZN)tH Mor NeNID) where: A=Area . N, =Nominalnumberofcells/mLatt, . N; =Meanmeasurednumberofcells/mLat t N; = Meanmeasurednumberofcells/mLatt; N.= Meanmeasured numberofcellsimLatt, =timeoffirst measurementafterbeginningoftest(hours) =timeof secondmeasurementaterbeginning oftest(hours) ta = time of n measurementafier beginningoftest(hours) Growth ateswerecalculatedforthecontrolandeachtreatmentgroupusingthefollowingformula Grotto- ON) where: N, = Meanmeasured numberofcells/mLatt, N, =Meanmeasured umberofcells/mLatt, ta =Timeofnmeasurementafterbeginningoftest(hours) Percentinhibition valueswerecalculatedforeachtreatmentgroupasthe percentreductionincell density,areaunderthegrowthcurveandgrowthraterelative tothecontrolreplicates.Thefollowing formulavasused: 000619 WILDLIFE INTERNATIONAL Lm. 14. PROJECTNO.: 454A-103A PercentInhib=iMteainoCenllDensity + Mean CellDensity esos X 100 `MeanCellDensitycose: Celldensities,areasunderthegrowthcurveandgrowthrateswereanalyzed statisticallytoestimate the EC10, EC50 and EC90 values (i.c., the theoretical test concentrations that would producea 10, 50or 90% reduction in each parameter, respectively) and 95% confidence limits at 72 and 96 hours. EC50 valueswerealsocalculatedforthe 24and 48hourtimeintervals. The ECvaluesand 95% confidence limitswere calculatedbylineayinterpolation using TOXSTAT Version 3.5 (5). Cell densities, areas under thegrowthcurve and growthrates at 72 and 96hours wereevaluatedfor normality and homogeneityof variancesusingthe Shapirteost-anWdBairtlletkt's'tesst, respectively. Thetreagrtoupmsweerenthten comparedto thecontrolusing Dunnett'stest. Resultsofthestatisticalanalyseswereusedtodeterminethe 'NOAECvalues. AnalyticalChemistry A Samplesof testmedium werecollectedfromthenegative controlandeach treatmentgroupat test -initiation, atapproximately 72 hoursandat testterminationtomeasureconcentrations ofthe test substance. Samplesoftestmediumcollectedattestinitiationweretakenfromtheindividualbatchesoftest solutionpreparedforeachtreatmentandthecontrolgroup. Samplescollectedat 72hourswerecollected from theadditional "analytical"replicates. Samplescollectedattesttermination were a compositeofthe remainingreplicatesfor cachtreaa ndt them cone tron lgrotup. Thesamples wereplacedinplastic (Nalgene)bottlesandwereanalyzedimmediatelywithout storage. Analytical proceduresusedinthe `analysisofthesamplesarepresentedin AppendixIIL RESULTS AND DISCUSSION MeasoufTresteConmcenetrantiotns: Resultsofanalysesto measureconcentrationsof PFOS inthetestsolutions arepresentedin Table 1 and AppendIiIxI. Nominalconcentrationsselectedforuseinthisstudywere5.7, 11, 23,46, 91and 183mga.i/L. Samplescollectedatthebeginningofthetesthadmeasuredconcentrations thatrangedfrom 82to98%ofnominal. Samplescollectedat 72hoursandtestterminationhadrecoveries thatrangedfrom AMENDED 000620 WILDLIFE INTERNATIONAL Lm. -15- PROJECTNO.: 454A-103A 82 10 105%and 90to 103%ofnominal,respectively.Whenthevaluesobtainedfortest niiation, at 72hoursandattestterminationwereaveraged,themean measuredtestconcentrationswere5.5,11,21, 4420d, 179 8 mg a6 i JL. ObseravndaMetasiuroemenntss. Measurementsoftemperatureandlightintensityareprescotedin Tables 2and3,respectively. The temperaturesrangedfrom23.60 25.8Candwerewithintherangeestablishedforthetest(24:2C). The lightintensity rangedfrom 3870to 4540huxandwaswithinthedesiredrangeforth test (approximately 3870104730 hux)(Tabl3e).Measurementsof pH were7.4 t0 75onDay 0andrangedfrom7.5to 8.4at 96hours(Table 4).ThepHofthe "abiotic"replicateattestterminawtasi7o.4n. TheeffofePcFOtS upon Selenastrum capriwacsdeoterrminnedbuyetvaluuatimng differenciesn celldensities,areas underthegrowthcurveandgrowthrates.Meanvalueswereusedtocalculategrowth inhfiorebachi24-thoiurpoerinod. Meancelldensities, areasunderthegrowthcurveandgrowthratesand theircorrespondingpercentinhibitionvaluesarepresentedinTables 5,6and7,respectively.Celldensity, areaunderthe growthcurve and growthratevaluesforeachindividualreplicatearepresentedin Appendices IV, V and VI, respectively. ECI0, ECS0 and EC90 values and 95% confidence limits calculatedfor each 24-hourintervalbasedoncelldensity, arca underthe growthcurveand growthrate are presentedinTables8, 9and10,respectively. Changesincelldensityindicatedthat exponeatial growthoccurredinthenegativecontrol replicates (Figure 1).Thecoefficientofvariation forcontrolclldensitywas 4%.Aft 72hoursofexposurcel,l densitypercentinhibitioninthe 5.5,11, 21,44, 86and 179mg a.i/Ltreatmentgroupswas 5.2,-1.9,-5.5, 11,72and 97%,respectively. Dunnett'stestshowedthatcelldensitywassignificantlyreducedinthe 86 and 179 mg .i/Ltreatmentgroupsincomparisontothenegative control (p<0.05). Consequenttlhye, NOAECfor72hourcelldensitywas 44mg ai/L.After 96hoursofexposure,celldensitypercent inhibiintthie5o.n5, 11, 21, 44,86and 179mga.i/Ltreatment groupswas 11, -5.1, -18, -12, 77and 99%,respectively. Dunnett'stestshowedthatcelldensity wassignificantlyreducedinthe86and 179mg a.i/Ltreagrtoupms(eps0n.05t). ConsequtehneNtOlAyE,Cfor96hourcel densitywas44mga.i/L. AMENDED 000621 WILDLIFE IINNTTEERRNNAATTIIOONNAALLULDo,.eee -16- TPEROOTJEECCTTNNOO..: 4455040A0-010038A8 `After72hoursof exposure,areaunderthegrowthcurvepercentinhibitioninthe 5.5, 11, 21, 44, 86 and 179mga.i/Ltreagrtoupmsweasn-2t.9, 1.3, -3.8, 5.8, 68and94%, respectively. Dummett' test showedthatareaunderthegrowthcurvewassignificantly reducedinthe 86and 179mga.i/Ltreatment groups(950.05). Consequently,the NOAECfor 72hourarea underthegrowthcurvewas44 img a.i/L. After96boursofexposure,areaunderthegrowthcurvepercentinhibition in the5.5,11,21,44, 86and 179mg 2/1treagrtoupmsweasn-8.t5,-3.3, -13, -53,75and 98% respectively. Dunnteesttstho'wesd thatareaunderthegrowthcurvewassigaificanlyreducedin the 86and 179mga. treatmentgroups (950.05). ConsequtehneNtOlAyE,Cfor96hourarcaunderthegrowthcurvewas 44mg a.i/L. After72hoursofexposure,growthratepercentinhibitioninthe5.5,11,21,44, 86and 179mg ai/L treatment groups was -1.1, -0.68, -0.72, 3.4, 31 and 82%, respectively. Dunnett's test showed that growthratewas significantlyreduced inthe 86and179mgai/L treatmentgroups (ps0.05). Consequently,the NOAECfor72hourgrowthraewas44mg a.i/L.After 96hoursofexposugrroewt,h ratepercentinhibition inthe 5.5, 11, 21,44, 86and 179mga.i/Ltreatmentgroupswas -1.9,-0.84, -3.0 2.0,27and 79%, respectively. Dunnett'stest showedthatgrowthratewassignificantlyreducedinthe86 and 179 mg a.i/L treatment groups (ps0.05). Consequently, the NOAEC for 96 hour growth rate was H4mgail. VisualandMicroscopic Observations `After 96 hoursof exposure, therewere10 sigasofaggregation, flocculationoradherenceofthealgae 1thetest flasksinthenegativecontrolor any PFOStreatmentgroup.Inaddtheirewtereinoonotincea,ble changesincellcolorormorphology whencomparedtothenegativecontrol,although afewcellsappeared enlargedinthe 86and179mga.i/Ltreatmentgroup. ReverosfGirobwithlInhiibittiyon The 179mga./Ltreatmentgroupwasmaximallyinhibitedattheendofthe96-hourexposure period. Aliquotsofthetestsolution weredilutedwithalgal mediumandculturedforfivedays.Basedon thegrowth observedinthe recovery phase,theeffectonalgalgrowthwasfoundtoalgistatic. Celldensities fortherecoveryphase arepresentedinTable 11andar illustratedgraphicallyinFigure3. AMENDED 000622 A WILDLIFE INTERNAe TIOe NAL Lo,. _ -17- PRPORMOJCETCTNNOO.::d4S54AA-1G03AA CONCLUSIONS "Theconclusionsofthisstudywerebasedonthemostsensitiveendpoint measured (i..,celldeasity, areaunderthegrowthcurveand/orgrowthrate). The 72-hourECS0,basedoncelldensity,ias 70mg a./Lvith95%confidencelimitsof44and 78mga.i/L. The96-hourEC10,basedoncelldensity,was 49mga../Lwith 95% confidence limitsof 43 and 50mg a.i/L. The96-hourECS0, basedoncelldensity, was 71mga.i/Lvith 95% confidencelimits of66and 73mga./L. The96-hour EC,basedoncell density,was 137mga../L with 95% confidencelimitsof 105and 153mga.i/L.The72-abndo96-uborur NOAECvalues,basedoncelldensity,areaunderthegrowthcurveandgrowthrate, were 44mga.i/L. Basedonthepresenceofvisiblealgalgrowthatrecoverytermination, PFOSwasconsideredtobe algistati, ratherthanalgicidal, attheconceatratiesotnesd. AMENDED 000623 I WILDLIFE Ie NTER RNATIy ONAo L Lon . pm + -18- PPRROOJEECCTTNNOO.::d455i4AA-M10033AA REFERENCES 1 U(dSra.ft)E,nOviPrPoTnmSeNnutamlbePrro8t5e0c.t5i4o0n0:AgAelngcayl. To1x9i9c6i.ty, STeireircssIa85n0dI-I.Ecological Effects Test Guidelines 2 OOErgCanDiGzuaitdieolnionfefEocronToemstiicngCoofopCehremaitciaolnsa.nGduDideevleilnoep2m0e1n.t.Par1i9s8.4. Algal, Growth Inhibition Test, 3 wAitShTMiMcrSotaalngdaaer.d AGuuisdet11291980.-90E, Standard Guidefor Conducting Siatic 96-Hour Toxicity Tests 4 The SAS System for Windows. North Carolina. 1996. Release 6.12, TS Level 0020. SAS Institute Inc. Cary, 5 West, Inc. and D.D. Gulley. TOXSTAT Version 3.5. Copyright 1996. Western EcoSystems `Technology, Inc., Cheyenne, Wyoming. 000624 ZWN LIOLLDLT IIPFEEE INTER RNATN IONAA L Lo.TIONAPPRRL OOJJEECCTTL NNOO.:.454TM 5344AA-1100. 33AA "19- `Table | _p--oner. `Summary of Analytical Chemistry Data TM Corporation TTeessttSOurgbasnainscme:: FrPeFsOhSwater Alga, Selenastrum capricornutum Dilution Water: __ "Nominal Freshwater Algal Medium Sampling Fieasured Viean Measured == E Concmgeantirlat)ion = Timel Concentraaitfi)on" Ce) onaceanltirla)t)ion NomoNiewfsnal 9"6 <o1q0Q 57 70 6a0m4 9% 584 5s 9% n 70 111207 9% 21 u 100 2 0 198 2 91 %7 2237.1 - 1" 20 a2s7 :" 9% % 63 9 70 88630 % 83 8 9 18 720 11896 9% m 9 8 183 7 150 169 2 % 188 #`0L-ihmoituorsfaaQtmtepuslteaiswtneirtoenci(o.LltlOeQca)tewtdafsio0mo.1i1nn5dim vidauag il./bLa.tchesoftest solutionpreparedfo thetreatmentandcontrol JSoutsampleswerecollefom theaddon) replicate Gio). "$97c62o-anhtnooudlr9gs6rahomuoppul.essawmeprleeccoolmlpeocstietdefsroofmttehstesaodlduittiioonnaclollEFe)ctreedpflriocmaea(acbhiootifc)t.he threereplicatesper treatment and. AMENDED 000625 WILDLIFEN INTERNE ATIONAL Lo. iia YPRROOJNEOCTTNNOO.:: 54504A3-1A03.A -20- Table 2 Temperature Measurements _Spo--nsor: 3M Corporation Test Substance: PFOS Test Organism: ~~ Freshwater Alga, Selenastrum capricornutum Dilution Water: __ Freshwater Algal Medium Time ~ Temperature (0) fu) Measurement | Measurement 2 o 26 22 1 us u2 2 28 20 3 25.1 253 . 4 258 249 : 5 27 : 24 6 256 u9 7 20 20 E 8 29 208 9 29 239 000626 JWI IILLDDLLN IITFEE T INTERE NATIR ONALN Lr. ATIOPRN POROEJCECTA TNNOO.::4L 4554A-410. 03A a1. Table 3 Light Intensity Measurements STpeosntsSourb:stance: 3PFMOCSorporation Test Organism: ~~ Freshwater Alga, Selenastrum capricornutum nt Dilution Water: bFrese hwateb r Algal eMediuprme Test ~ Day No.1 No.2 No.3 No.4 Nos 01 33991400 3a88n0 44434000 31961000 0381700 2 4000 4290 4310 4540 4170 34 4212000 34949000 43385900 44017600 44214400 5 3910 a120 4180 4200 340 67 44138000 44128000 41392500 44240300 44307800 8 4010 4230 4180 4230 4450 9 4150 4090 4240 4350 4270 000627 "NWIILLDDLLIITFEE IINNTTEERRNNAATTIIOONNAALLLLom.. 2. FPPRROOJJEECCTTNNOO.::454544AA--110033AA Table 4 PH Measurements ---- Sponso-- r: 3M Corporation Test Substance: PFOS Test Organism: ~~ Freshwater Alga, Selenastrum capricormutum Dilution Water, _ Freshwater Algal Medium `Mean Measured PH Measurements Concentration ~ (mgai/L) 9 Hours! "Negative Control 75 96 Hours 81 55 74 82 n 75 82 21 75 84 "4 74 83 8 74 78 1 74 75 169 (Abiotic) = : 74 0-hoursamples werecollectedfromthebatchesoftestsolution preparedforthe treatmentand control groups at test initiation. * 96-hoursampleswerecollectedfromthepooled replicatespertreatmentandcontrolgroup. AMENDED 000625 a abies etn Desi ntPentonfiExch2s elDring heTe FROCTNO: ssn -- T[okCrpi riveA_ pSka cpcmm------ DiMCveorimmieersrtNo vTpseE ryi MCp E yote Ma-- l a e-- G pen Cees Din wm Dw mme E Dme ume seeaaaume ss mw ow mm ox ase a seem a w ET u mow me as ese as sam a " we oa we se ssw ou mm wm " me ow ww 8 mw on aww IV ncmpnT lSeSnswmVmpeis sscamhoe t in Dt wer <L0% vse nAaesnn in tt 4 bigDt 045. 28$ 82 mom ue PROJECTNO: 454i Tubes MeanAvesUnderthe ronsCurvesdPeco binforExch 2 Hour ealDuin heTs! -- TowSham BFS ---- DTiosoOnpWia:trF_rFertoAAllbss,vSeesdleinca, eprom TVeetmCMoeesiwmriwctn NZewitPoeat MenCmRen MemTenhem Maw n mPes TT ewaiGne) Ave Gibin W Awa bin mAmm A bem wmAm le ss mee 6 mee 43 ome 29 smo 4s u mee 1s meme 89 0m 13 sms 33 n 0 A ewe 28 mow as saome " Bw0 8 2omme 34 swe ss somew 53 w" wae 3 eww s sme 6 name Vioc i m ingS2e A0S6017 Manoin]clemayaG7tgusy oor oi womme wn IIndincteetsnsssipiiggcaienddfiftlreonscceffroommr thheneoggpaatvtievoescoonuttroll3atW762iBhuorusrsvwiiinngggDDDeuumnentscsvcsp9zo<0t000y9).,. 233 a8 ot0 as. FROECTNO: shin Tae Mtnrots 4Peo ii frFxch24 slDuro Te TTokOopSi rw 70i8 teAn,crt cpm DTe inCca.s_ rT eMomsA teePtene Moi m sPeet pM oeR Mai n ote a avid) GowiRus lke Grau lin Gifu a bie Goes lane 5s wom omm oo sw au ams as uI . a wasn ome ae own am oem ao " wa ees a1 oo uo emma " wm ow ems om ow a ww ow TVsicsipogGw$e1s5 rCT oratngi heeitmG8 ryt a Drts onor 009) 2 wwe ieEcdoe he pie ar 43 otheDe 00) 388 RaB Jere a FRORCTNO: ssa aes CIO, S020 ECOValesBt CllDensityOrr he9HosEposPosi TTTeokeOpnie WF10r8oamAel,Scrat cpm frst scotindrrfeor min ove nwenn Tc-- an cwaen -- a-- TT i i ET ton amin - u nen avant - nom ow come Pe, IN Dowites wtom son n comin w reais 8 a8 moe "ae PROJECTNO: 454A-103A Tables CIO,ECS0aod ECD ValuesBasedcnAraUndertheGrom CurveOver he 86 HourExposure Period -- TToonp F7-- 0r8 iAlp.Sens prion Diver Feo AgMe,oC Er Tine s(cgaii0n) mLaiisn) (osgeesin) Leien) Teri TotDemin = wn Ta 16 an Noten - " Grutiis tines " wuss sin Stine wis 2 en (ogscesi0n) TotDeed NetDtriond ws us TgLaiiC mni) = - sans istiss 8S 4[ AMENDED a PROTECTNO: A100 Teno e T [EereeeCIO,ESD E90Vl BtnGre nR-- tOre S-- H x-- posPee d e Toovte FmeteeAny irumecpr sc = co rToe =a cay cnn tn aso:n I ra=ca I = hn arent . = Sy 4 @ es dems - i we2hnenrrr spoaos t sweiinn R oomm ee-= Tee sg8 88 mom WILDLIFE INTERNATIONAL Lm. 29. PROJECT NO.: 454A-103A `Table 11 Cell Densities for the Recovery Phase STeet Substance: TDoisltutOirognanWoitoemr::_ WPMFCOS. FFrreesshhwwaatteerrAAllggal, SMeeldenisutrum capricormutam Mean Measured Cell Densities (Cells/mL" `Test Concentration (mg ai/l) Dayo Day3 "Negative Control Rep. A. 10,000 1,220,000 Days 6,420,000 179" 1,000 35,000 1,180,000 T Thetreatmentgroupwasdilutedto aconcentrationofthe testsubstance thattheoreticallywould not inhibit growth. : :Due tothemethodusedto prepare recoveryphasetestsolutions,initialcelldensities werenot equivalent throughout the treatment groups. 000635 AMENDED WILDLIFE INTERNATIONAL Lm. -30- PROJECT NO.: 454A-103A Figure 1. NegativeControlAlgalGrowth,ExpressedinCellDeasity,Duringthe96-HourExposure. 10000000 1000000 100000 10000 1000 Mean Cell Density (Cells/mL) ~=--Negative Control 2 48 72 % - 000636 AMENDED WIL LDLE IFENINETERRNAO TIONY AL Lo. enfin -31- Figur2e. ConcentratCuirveo,Enxp-reRsseedsinCpelolDneassiety PROi JECT NO.: s 454A-103A 10000000 1000000 100000 . 1000 Mean Cell Density (Cells/mL) - : --a--Negative Control --e--5.5 mall ----11.mgnL 21 mgt --o--44 mon 1----7868momltg 2 8 2 9% . Exposure Duration (Hours) i ; 000637 AMENDED WILDLIFE INTERNATIONAL Lm. "32 Figu3re-RecoveryPhaseResponseCarve, ExpressedinCel Deasity PROJECTNO: 454A-103A 10000000 1000000 100000 ` 1000 100 0 Coll Density (Cells/mL) : ' --8--Nogativ-e Control --a--179 mg . . . 12345 BN Exposure Duration (Days) = 000638 AMENDED WILDLIFE INTERNATIONAL Lo. .3- PROJECT NO.: 454A-103A APPENDIX1 Freshwater Algal Medium' Sponsor. SM Corporation Test Substance: PFOS Test Organism:~~FreshwaterAlga, Selenastrum capricornutum Dilution Water: _ Freshwater Algal Medium "Nominal Compound Concentration MsCLO6H0 216 mg CaCho2H:0 440 mgL Ry 0185 mg/L MaCLo4H:0 ZC; 0342186 mglg FeCle6H:0 01598 mg/L CoCLO6H:0 128 ug Na:MoO,#2H:0 726 ug CuCh92H:0 002 ug Na;EDTA2H,0 NaNO, 02350500 mmgg/L . MgSO TH:0 KHPO, 1870 1044 mmgg NaHCO. 150 mel ThepHvasadjus1t0e7.d5 + 0.1 using 10% HCL 000639 WILDLIFE INTERNATIONAL Lto. a PROJECT NO.: 454A-103A APPENDIX II AnalysesofPesticides, Organics, Metals and Other Inorganics saeesswvcovoEDmCon umoy in Wildlife International Ltd. Well Water' T HEET . &A = SEp e : om om = 2 EEBTeHC.-- <o PPPoooswml0008 3gL BuBtE, : i Poem = BHBEEuE. PPHoE ol = BF HotterBoonie PCB.1221 i BBHE PCB-1232 PCB-1242 cote ng Or rics Amiay=a Coolcga? | f= ELoa?w PE 3 0.005 =wl < 0260 ri - i <iPoBm00m .276200 Fg=oaLFL ) 3i 48 aEF Peo EB Y] omg. <Doo10m90 awl BFe= B mF Z M3E AleBemby WaiteIcmstooLnil.forspi oie onNovember Shough7, 1997. 000640 WILDLIFE INTERNATIONAL Lm. 35. APPENDIX Il PROJECT NO.: 454A-103A `THE ANALYSIS OF PFOS IN FRESHWATER ALGAL MEDIUM IN SUPPORT OF WILDLIFE INTERNATIONAL LTD. PROJECT NO.: 454A-103A 000641 WILDLIFE INTERNATIONAL Lm. -36- PROJECT NO.: 454A-103A REPORT APPROVAL SPONSOR: 3M Corporation TITLE: PFOS: A 96-HourToxicity Test with the Freshwater Alga (Selenastrum capricornutum) "WILDLIFE INTERNATIONAL LTD. PROJECTNO.: 454A-103A PRINCIPALINVESTIGATOR: Rayna I Van Hoven, Ph.D. Scientist MANAGEMENT: stn 5}ip Willard B. Nixon, Ph.D. Manager, Analytical Chemistry . He 4-00 DATE sith DATE 000642 AMENDED WILDLIFE INTERNATIONAL Lm. -37- PROJECT NO.: 454A-103A Introduction Freshwater algalmedium sampleswerecollectedfromanacutetoxicitystudydesigoedtodeterminethe. effects of PFOS (Perfluorooctane Sulfonic Acid Potassium Sal) to the freshwater alga (Selenastrum capricornutum). This study was condubycWitldelidfe International Ltd. and identified as Project No.: 454A-103A. TheanalysesofthesewatersampleswereperformedatWildlifeInternationalLtd.usinghigh performanceliquidchromatography withmassspectrometricdetection (HPLC/MS). =Samples were receivedforanalysisonApril12, 15and 16,1999andwereanalyzedoneachsamplereceiptday. `S Testubsantd Ina ternn alStcande ard Thetestsubstanceusedfortheanalyticalportionofthisstudywas WildlifeInternationalLtd. identification number 4675. Thetestsubstancewasusedtopreparecalibrationstandardsandmatrix fortificationsamples. Theintemalstandardwasreceivedfrom 3MCorporationon July2, 1998andwasassignedWiklife IntemationalLid.identification number4526 uponreceipt. Theinternalstandard, agranularmaterial,was identified as: 1H, 1H, 2H, 2H Perfluorooctane Sulfonic Acid, Chemical Abstract Number: 27619-97-2. `Thestandard wasstoredunderambieatconditions AnalyticalMethod "Themethodusedfortheanalysisofthefreshwateralgalmediumsampleswasdevelopedat Wildlife IntemationalLtd.and entitled "AnalyticalMethod Validation for the.Determination ofPFOSin Freshwater, SaltanwdaAlgtaleMerdia,". ThismethodologywasincludedasAppendix I of Wildlife Intemational Lid. protocol mumber 454/011299/MVAL/SUB454. It was based upon methodology probyv3MiCordporeatidon. Sampleswere diluted in a 50%methanol : 50%NANOpurewatersolution containing 0.mg14H0PF0OS (intemal standard)/L. and 0.05% formic acid (v/v) so that they fol within the calibration rangeofthe PFOSmethodology. Concentrations of PFOS inthestandardsand sampleswere determinedbyreverse-phasehigh performance liquid chromatography using a Hewlet-Packard Model 1100 High Performance Liquid 000643 WILDLIFE INTERA NATIONAL Lm. itm 38. TPRROOJEERCTTNNOD:;S45S4AS-10A3A Chromatograph (HPLC)with aPerkin-Elmer API 100LC Mass Spectrometerequippedwith a PerkinElmer TurbolonioSnpsoruarcye. HPLCseparationswereachievedusing aKeystoneBetasil Cio analytical column (100mm x 2mm LD., 3 umparticlesize). Theinstrumentparametersaresummarized in Tabl1e. Amethodflowchartisprovidedin Figure1. Calibration standards of PFOS prepared in a 50% methanol : 50% NANOpure water solution containing 0.100mg4H PFOS (internalstandard) and0.05%formicacid (v/v), ranginginconcentration from 0.00229to0.0457mg a.i/L wereanalyzed withthesamples.Lincarregressionequations were. encratedusingpeakarea responseratios (PFOS intemalstandard)versustherespectiveconcentration ratios(PFOS : internalstandard)ofthecalibrationstandards. Atypicalcalibrationcurveispresentedin Figure2. Theconcentrationof PFOSinthesampleswasdeterminedbysubstitutingthepeakarea responseratiosintotheapplicable linearregressionequation. Repreisonechrnomtatoagrtamsiofvloew. `andhighcalibration standardsareprescatedinFigures 3and4,respectively. `Themethodlimitof quantitation (LOQ)fortheseanalyseswassetat0.115mga.i/Lcalculatedasthe prodouftchte lowest calibrationstandardanalyzed (0.00229 mg ./L)andthedilution facotfothre matrix blank samples (50.0). `Threematrixblanksampleswere analyzedto determinepossibleinterference. Nointerferenceswere GbservedatorabovetheLOQduring samplesanalyses(Table2). Arepresentativechromatogramof a matrixblankispresiennFitguere5d. Freshwater algalmedium wasfortifiedat0.915, 45.7and 220mg 2:/Landanalyzedconcurrently viththesamples todeterminethemeanproceduralrecovery(Table3). Sampleconcentrawteireonnost correctedforthemeanproceduralrecoveryof99.1%. Arepresentativechromatogramof amatrix fortiispfreiscacteadintFiiguoren6. 000644 AMENDED WILDLIFE INTERNATIONAL Lm. -39- PROJECT NO.: 454A-103A ExampleCalculations `Sample number 454A-103A-2, nominal conceatration of 5.7 mg a../L in freshwater algal medium. Initial Volume: 0.100 mL Final Volume: 25.0 mL DilutionFactor: 250 PFOS Peak Area: 164427 Internal Standard Peak Area: 240533 Peak Area Ratio: 0.6436 Calibration curve equation. Slope: 3.43926 Intercept: 0.03327 Curveis weighted (15x). PROS (1gai/L)atinstument = o( ekaka2r5i e2aarat0ion = (Y-t intercept))r x151S,.o CCoonncceenntt) rraattiion Slope (0.6836 ~0.03327) x 100pgai/L 343926 = 189pgaill Note: LS. = internal standard. PFOS (mgai/l)insample = --Po FOS(ug .i/L)o atinstrument x" DilutRionAFaActoTr 1000 ug/mg 189x250 a 1000 000645 AMENDED WILDLIFE INTERNATIONAL Lm. 40 PROJECT NO.: 454A-103A = ATmgaill Percentof Nominal Concentration = PP2FF0OO0SS(C(mrmgegnaa..Lii//ILL)) niRnomisnaBamlple Calculated recovery: 82.0% Note: manual calculation may differ. : RESULTS `SampleAnalysis, Freshwater algal riedium samples were collected from the acute toxicity study with th freshwater alga (Selenastrum capricornutum) attest initiation, April 12, 1999 (Hour 0),onApril 15, 1999 (Hour 72), and at test termination, April 16, 1999 (Hour 96). The measured concentrations of PFOS in the samples collcted at niioaftexpoosunreofth testorganisms(Hour0) ranged rom 82.0 0 8.1% ofthenominal concentrations, Samples collected at Hour 72 had a measured concentration range of 91.7 to 105% of nominal values. The Hour-72 abiotisamplewas 81.9%ofthe nominal concentration. Samples collected attest termination (Hour 96)had a measured concentrationrangeof 90.3 to 102%ofnominal values. The Hour-96 abiotic sample was 103%ofthe nominal concentration (Table 4). A representative chromatogram ofa testsample is showninFigure 7. 000646 AMENDED WILDLIFE INTERN NATO IONALILr. ssimmenTPRRIOJBEECTTNNOO.::S4S54AA-A103A a1 Table 1 `Typical LC/MS Operational Parameters E INSTRUMENT: Hewlet-Packard MoS del 1100 High Performance Liquid eCqhuriopmpaetdowgirtahpahPweirtkhina-PEelmrekriTnu-ErlbmAoePrIl1o0n0iLoSCnMpsaorusrascyeS.peOctpreormeatteeridn selective ion monitoring mode (SIM). ANALYTICAL COLUMN: Keystone Betail Cys column (100 mm x 2 mm LD. 3 pum particle size) OVEN TEMPERATURE: : 30C STOP TIME: 10.0 minutes FLOW RATE: 0220 mL/minute MOBILE PHASE: 72.0% Acid Methanol :28.0% NANOpure Watercontaining0.1% Formic INJECTION VOLUME: 2504 PFOS RETENTION TIME: Approximately 6.6 minutes INTERNAL STANDARD RETENTION TIME: Approximately 4.5 minutes PFOS MONITORED MASS: 498.6amu INTERNAL STANDARD MONITORED MASS: 4267 amu 000647 WILDLIFE INTERNATIONAL Lt. a2 PROJECT NO.: 454A-103A `Table 2 Matrix Blanks Analyzed Concurrently During Sample Analysis (@`5N4uAm-b1e0r3A) MAB-1 MAB2 Sample Type Matrix Blank Matrix Blank Measured Concentration of (mPgFaOiSl'L) <LOQ <L0Q MAB-3 Matrix Blank <L0Q `Thelimitofquanti(tLOaQt)wiaos n0.115mga.i./Lbaseduponthe productofthelowestcalibration standardanalyzed (0.00229 rig a.i/L)andthedilutionfactorofthe matrixblank samples (50.0) 900648 AMENDED WILDLIFE INTERNATIONAL Lo. a. PROJECT NO.: 454A-103A Table 3 Matrix Fortifications Analyzed Concurrently During Sample Analysis Sample Number (454A-103A7) MAS MAS4 MAST "Concentrationsof PFOS mg ai/L) Fortified Measured 0915 0884 0915 110 0915 102 Percent Revered %6 120 12 MAS2 457 a3 902 MAS-5 Lo4s7 484 106 MASS toast 414 906 MASA 20 210 952 MAS3B 220 200 91.7 MAS3C 20 209 950 MAS 220 21 101 MAS 220 202 919 Mean = 99.1 Standard Deviation =9.75 ov =98 N= "Note: Results and corrections for new test substance purity were generated using MacQuan version 1.5 soafndtmanuwalcaalcurlatieons. Valueshavebeen roundedforreporting purposes. 000649 AMENDED WILDLIFE INTERNATIONAL Lm. 4 PROJECTNO.: 454A-103A Table 4 Measured Concentrationsof PFOS in Freshwater Algal Medium Samples from a Freshwater Alga Acute Toxicity Test `Nominal Test Concentration (mgai/L) 00 Sample Number (454A-103A7) T 8 15 Sampling Time (Hours) 0 7 % POS Measured, Concentration' (mgai/) <10Q <10Q <10Q Percent of Nominal =~ 57 2 0 9 7 1 % an 820 604 105 584 101 un 3 0 107 898 10 7 12 96 n 9 121 102 2 4 0 198 862 n 7 231 101 18 9% 207 903 46 5 0 12 7 19 % 27 934 419 91.7 463 101 1 6 0 13 7 20 9% 3 910 0 940 83 %5 183 7 0 14 7 2 9% 1 98.1 186 102 mn 94.0 183 14A 7 150 819 (Abiotic) 2 9% 188 103 Note: Results and corrections for new est substance purty weregeneratedusing MacQuan version 1.5 software and manual calculations. Values have been rounded for reporting purposes. "The litof quantitation (LOQ) was 0.115 mg a.iL based uponthe productofthe lovist calibration standard analyzed (0.00229 mg .i/L)andthe dilutionfactorofthematrblianxk samples (50.0). 000650 AMENDED A WILDLIFE INTRERNNAATOIONNAL Lo. re FPRROOEJECCTTNNOO.: 445M4AA-d1003AA METHOD OUTLINEFORTHEANALYSIS OF PFOS IN FRESHAW LGA ALT MEE DIR UM Preparematrixfortification samplesbyspikingtherequisitevolumeofPFOSstocksolutionsdirectly intofreshwateralgalmediumusinggas-tightsyringesandClass Avolumetricflasks. i Dilutematrixfortificationandtestsamplesintotherangeofthe calibrationstandards by partiallyfilling Class Avolumetric flaskswith 50%methanol:50% NANOpurewatersolutioncontaining 0.100mg 4H PFOS (internal stan andd0.a 05%r ford mic) aci/ d(vL /v).Add the appropvroiluametoef sampleandbringthe flaskto volumewiththedilutionsolvent.Processthematrix blank sampleusing thesamedilution andaliquotvolumeasforthelowestfortification level.Mixwellbyseveralrepeat inversions. v e Ampulate samplesandsubmitforLC/MSanalysis. Figure1. Analytical methodflowchartfortheanalysisof PFOSinfreshwateralgalmedium. 000651 A WILDLIFE INTERNAATIOA NAL Lo.renter a6 TPRROJOETCTHNOO.:S45A4A-N103SA 2.00 : : 150 5 10 050 0.00 0.000 0.100 0200 0.300 0.400 0.500 Concentration (Ratic) ~*~ Figure2. Atypical calibration curve for PFOS. Slope = 3.43926; Intercept = 0.03327; r = 0.9986. Curve is weighted (1/x). 000652 AMENDED WWIILLDDLLIIFFEEIINNTTEERRNNAATTIIONALLLLDm. ar. PPRROOJJEECTNNOO.: 44s5t4aA-1l003sAA 100 20 % 80 0 60 ntonsity: 2849cps 3 23, "50 40 30 2o0 u A138 3T1a e2l5% 9a1m 1S3o1s 1651 178517 2811s | TSmane Figure3. Arepresentativeion chromatogram of a low-level (0.00229 mg a.i/L) PFOSstandard. 000653 AMENDED W--I_L--DLIFE INTERNATIONAL Lo. ae PROJECI TNO.: 454A-m103AA To o i 185 Intensity: 32143 cps ne 8 . . o 5 4 3 2 P 135 ' : |: 24 1s Ai 3$13 6215 9a1m 1S2e1s 1651m 17815 2181s TScmaon Figured. Arepresentativeionchromatogram of ahigh-level (0.0457mga.i./L) PFOS standard. 000654 AMENDED WWIILLDDLLIIFFEE IINNTTEERRNNAATTIIOONNAALLLLoo.. snormcrnos PROJECT NO.: assaisa 454A-103A __ 100 3 ---- w90 : : T w . -50 " - " wl Li Redes TAL rae TY a Th WW wm Figur5eS. Arepresentativechromatogramof amatrixblanksample(454A-103A-MAB-1). `Thearrowindicates theretentiontimeof PFOS. 000655 SWIULDDULIPFEEIINNTTEERRNNAATTIIOONNAALLALTmS., mmmePRROTJEEECETNNOO.L:44A54AAI-1B03AA -50- To 187 intensity: 9104 cps 9 - 8 .7 & . 5 4 = 8 137 2 1 24 11s o= es o 31Tw 6215% 9a1m 1S21e 1651s 178815 2161s TSeiamne Figure 6. A representative chromatogramof a matrix fortification sample (454A-103A-MAS-1). 000656 WILDLIFE INTERNATIONAL Lm. sie PROJECT NO. 454A-103A To : . { 161 intensity: 11161 cps 8 7 s 5 4 # 140 2 1 25 118 ~ : S1%161255 9a11 153016 1651% 178517 28118'3 | TSiamne Figur7e. Arepresentativechromatogramofatestsample (454A-103A-2). 000657 WILDLIFE INTERNATIONAL Lm. 52. PROJECTNO.: 454A-103A APPENDIX IV CellDensity forEachReplicatePerTreatmentOverthe96-HourExposurePeriod E TesSubsmce: PROS E -- TDeisltuiOorngWmetieor:_ ~~ FFrreesbawtaetre AAllgga,a MSeeldenisutramcapricorn A Conocnttion Col Dees Cala TR(mgaC ill) ReplAiBcate c 24MBHOo0uD0rs. 31.000 418I3H0o0Du0r0s 125000 7200H50o0u00rs0 95000 9o263H6oo0u0rm0s0 2640000 ss a5 223900000 11386000000 5000000000 23.010800000000 35000 134000 25000 2540000 un AB 320700000 112045000000 665600000000 22764800000000 c 31000 134000 aso 320000 2 - a5 2360000000 110312.000000 846500000000 33304800000000 c 2500 128000 0000 3300000 " AB c 230000000 115316.000000 27000 13500 5010500000 330000 332043220000000000000 " AB 3178000000 67500000 211365000000 576000.00000 c Zo 6000 162000 470000 m BA 11580000 Z35o0o0 2w1.w000 53000000 c 1000 26000 500 26000 "TocheambmeirlocyilelldGeneelydoafsihteysofoacpkprcoitzartewlays10d,00elvrait etdiieo v(o0lhouumrse)w.as SATS] to eachVt 000658 AMENDED WILDLIFE INTERNATIONAL Lm. 5. PROJECT NO.: 454A-103A APPENDIX V AreaUndertheGrowthCurveforEachReplicate PerTreatmentOverthe96-Hour ExposurePeriod `TSTeposontusOSorru:gbsamne: PF3RMOrCSoreporsatAilohgna.,oStlesr capricorn DiluiMoenaWnaMtere_adFreerAle Medium Co foe Um nieBt eGrowe Gore Conogcantianti)on Replise --0 2--4ous 0_48Hows R_0E.72HoSws R __0-96Hous TewCmm A5 B26R0O00 2109020000 I0T5S200L00 5S19m12e00e0 c 252000 TROD 90800 46464000 ss a5 21586000000 T19B608000. 2B0TB0AM0D 27780440000000 N0000 2000 1095600 S460 n A5 204000000 1I62T00O00 1903904000000 4581050004000000 c 252000 92000 1080000 36760000 2 AB 21902,00000 2T0S00O0 BBEsmA0K 6752840000 : c 216000 TRO 163400 36304000 " BA 2604000000 2129020000 195I6Z4R000 45961504200000 c 204000 Toso 70 se4s000 5 BA 5264000000 1F06800000 24488m0K000 11433364800000 c 144000 TOON 2900 10320000 mw BA 9600000 326000000 A S260000 1$4102400000 c o 192000 40000 58000 000659 AMENDED WILDLIFE INTERNATIONAL Lm. san PROJECT NO.: 454A-103A APPENDIX VI GrRoatw efot r Bh achReplicate PerTreatmentOverthe 96-HourExposure Period `STTpeeoatnsSOowgrbu:sniasmmc:e FP3reMOsShCowraptoerartAiloan:, Seles capriconutim Dilu"tiMoenaWneeMre.am_redFreshwaterAla Motion Grow a Congceantirant)ion Replicate w 0-24Mows _ 0_de 8Hows 0.7Howt s 0-9 Hous C B 00457 T 005% 00570 rey c oom 00526 o0se2 aos ss AB o00u37 0o0s54s4 . 0a0o60s8 a0o0s6s0s oo 00541 00574 aos n AB 00u4s1s4 000054205 0o0o5s5e92 aa0ossss c oom 00541 00574 ave 2 AB o0o0s3sss 0000555318 00006s1 o000s509s7 c 00m 00531 00s) 0060 " AB aaooss 0000554646 a0o0s5e%r o00o8s9s5 c oon ose 00509 00608 AB oaaotsiss [0r0r6 aoonaes aooots c 00 aos aos 0001 1m AB o00n16s9 ocoulse i 0o0m10e3 o00o1s174 c 0000 0019 oons 00010 000660 AMENDED WILDLIFE INTERNATIONAL Lm. Zs PROJECTNO.: 454A-103A APPENDVIIXI `ChatonPrgoteocsol `Thisstudy wasconductedinaccordancewiththeapprovedProtocolwiththefollowingchanges: 1. Tcheoprontoccoelwanandsttaemsretsnuadbesttdatnioceaondudmnbtehsre.proposedexperimentalstartandterminationdates,test 2. Theprotocol wasamendedtospecifytheanalyticalmethod. 3. Theprotocolwasamendedtorepeatth testwith ahigher estconcentration. 000661 WILDLIFE INTERNATIONAL Lo. -56- PROJECTNO.: 454A-103A APPENDIX VIII PersonnelInvolvedintheStudy `Thefollowingkeypersonnelwere involvedintheconductor managementofthisstudy: 1. HenryO.Krueger, Ph.D,,Director,AquaticToxicologyandNon TargetPlants 2. WillarBd. Nixon,Ph.D.,Manager,AnalyticalChemistry 3. RaymondL. VanHPoh.Dv,,Seciennti,st 4. KurtRDroStenioarBirolog,ist 5. MarkA.Mank,LaboratorySupervisor 000662 WILDLIFE INTERNATIONAL Lm. L574 PROJECTNO.: 454A-103A APPENDIIX ReportAmendment 1. OriginalReport: Pa14g,6eands36 Amendment: Tnhumebpeargs,esawnedrneewchsainggneadtutroesinacnludddeattheesamdeuendteodtrheepaodrdtidtaitoen,orfevtihseedrpepaogret amenasdApmpeendinxItX. Reason: Toreflecttheissuingofanamendedreport. 2. OriginalReport: Page2 Amendment: Thecompliancestatementwasrevised. Reason: To clarifyhowthetest substance wascharaclerized. 3. OriginalReport: Page 10 Amendment: Informationprovidedbythe Sponsorreflectingthereanalysisofthetestsubstance, siencctliuodni.ngthereanalysisdateandthepu-rity, wasaddedtotheTestSubstance Reason: Toreflectthe currettestsubstanceinformationprovidedbytheSponsor. 4. OriginalReport: Entirereport Amendment: sAulblstteasntcseuabssdteatnecrecmoinnceednbtyrtathieonSspownesroercihnaanrgeeadnatloyrseifsolefcttthheteepsutrsiutbysotafnctehe(tFeCs-t 959,89L%o,t21T7h)e.ceTretsitfciocnacteenotfraatniaolnyssoirsidgaintaeldlyMawrecrhe'b9a,se2d0o0n0tinhdeirceaptoerdteadppuurriittyyooff 9co0n.c4e9n%tr.ationTsh,ermeefoarseu,redallcontcesetntrsautbisontsa,ncEe Ccovnacleunetsr,atainodns,NOiAncElCudivnagluensomwienrale recalculatedandreportedas mg 2.1L.basedonthe90.49%purity. Reason: "Toreporttheresultsofthetestbasedonthetestsubstancepurityof 90.49%atthe reqoftuheeSposnsotr. 000663 AMENDED WILDLIFE INTERNATIONAL LTD. PROJECT NO.: 454A-103 Page 1 of AMENDMENT TO STUDY PROTOCOL STUDY TITLE: PFOS: A96-HOUR TOXICITY TEST WITH THE FRESHWATER ALGA (Selenastrum capricornutum) PROTOCOL NO.: 454/110998/SEL-96H1/SUB454 AMENDMENT NO.: 1 SPONSOR: 3M Corporation PROJECT NO.: 454A-103 EFFECTIVE DATE: January 4, 1999 AMENDMENT: Page2 Add: Experimental Start Date: 2/19/99 Experimental Termination Date: 2/23/99 "Test Concentrations: Negative Control, 6.3, 13, 25, 50 and 100 mg a.i/L `Test Substance No.: 4675 REASON: The above information was not known when the protocol was signed by the Study Director. AMENDMENT: APPENDIX II, Page 16 - Add: Liquid Chromatography Mass Spectrometry (LCMS) Method for the Determination of Perfluorooctane Sulfonic Acid, Potassium Salt (PFOS) in Freshwater, Filtered Saltwater and Algal Medium. REASON: To add the analytical method to be used in the study. Sort] STUDY DIRECTOR aL LABORATORY (AGEMENT do 6 ond SPONSOR'S REPRESENTATIVE I al9(9 DATE aff DA 2/16/19 DATE 000664 I iui sby fi 2h [EllWILDLIFE INTERNATIONAL LTD. PROJECT NO.: 454A-103 Page of | H AMENDMENT TO STUDY PROTOCOL oH STUDY TITLE: P(SFeOlSe:nastArum9c6a-prHiOcUorRnuTtOumX)ICITY TEST WITH THE FRESHWATER ALGA PROTOCOL NO.: 454/110998/SEL-96H1/SUB454 a SPONSOR: 3M Corporation AMENDMENT NO.: 2 PROJECT NO.: 454A-103 EFFECTIVE DATE: April 8, 1999 a AMENDMENT: Page2 H Experimental TerminationDae: 2/23/99 Change: Experimental Start Date: 2/19/99 `Test Concentrations: Negative Control, 6.3, 13,25, 50 and 100 mg a.i/L. Ho To: Experimental Start Date: 4/12/99 `Experimental Termination Date: 4/16/99 I Test Concentrations: Negative Control,6.3, 13,25, 50, 100and 200 mga.i./L. - REASON: Tmhiecrotsecsotpwei.llAbneardedpietaotneadlbteesctacuosnceecnetlrlactoiuonntwsawseardedendoitnamnadaetweimtpht tahoebmtascinytEoCm9e0tevrlaunesd. a AMENDMENT: EXPERIMENTAL DESIGN, Page 3 H Change: a`tTaerrg.et concentrations will not exceed 100 mg/L or the solubility limit of the test substanicne H To: Targetconcentwrilaltnoiteoxcneesd 1000mg/Lorthe solubilitylimitof thetestsubstancein water. i REASON: Thenewnominalconcenetxcereda1t00imgoain/Ls. u PESAN STUDY DIRECTOR 2/8177 DATE Ho wd A m Ja Reds nu SPONSOR'S REPRESENTATIVE H cusatonenents 4 fo Yla1 24 DA 000665 Qf lorebsy JB. 34pTrd { a PROTOCOL = PFOS: A96-HOUR TOXICITY TEST `WITH THE FRESHWATER ALGA (Selenastrum capricornutum) i US. Environmental Protection Agency HH Series 850O- PEcPolSogNiucamlbEefrfe8c5ts0.T5e4s0t0Guidelines `OECD Guideline 201 mu ML RsNe U3 Submitted to Envir3oMnmeCnotraplorLaatbioonrsory P.0. Box 33331 St. Paul, Minnesota 55133 WILDLIFE INTERNATIONAL LTD. 8598 Commerce Drive Easton, Maryland 21601 (410) 822-8600 November 9, 1998 PROTOCONOL.: 454/110998/SEL-96H1/SUB454 000666 3M LABREQUEST NO. U2723 u - JA WILDLIFE INTERNATIONAL ro. H WITH THE FPRFEOSS:HWAA9T6E-RHAOLURGATO(XSIelCeInTasYtTruEmScTapricornutum) H SPONSOR: 3M Corporation `Environmental Laboratory H PSt..0.PaBulo,xM3i3n3n3e1sota 55133 ul `SPONSORSREPRESENTATIVE: Ms Susan A. Beach TESTING FACILITY: Wilde Intemational Lid Ho `8E5a9st8onC,oMmamreyrlcaendDr2i1v6e01 STUDY DIRECTOR: Kurt Drottar Senior Aquatic Biologist Ho HH LABORATORYMANAGEMENT: HDeirnercytoOro. fKrAuqeugaetri,cPThoDx.icology & Non-Target Plants FORILABORATORYUSEONLY _ mu | Proposed Dates: | |] | Eoxperoimebntalme_TommmoEnxperDimenutals | prec: 4544-1e 03 s | || |] Test ConcentrA ations: 1 | TestSubstanceNo: ReferenceSubstanceNo, (ifapplicable): | = [1 ml || ma A or AN STUDY DIRECTOR /2/4(78 DATE LAB {TORY {AGEMENT SPONSOR'S REPRESENTA pfye DATE 2/1 DAT 000667 PROTOCOL NO.: 454/110998/SEL-96H1/SUB454 3M LAB REQUEST NO. U2723 i J WILDLIFE INTERNATIONAL Lo 1 = INTRODUCTION 1 Wildlife Interational Ld. will conduct a 96-hour toxicity test with the freshwater alga, `Selenastrum capricomutun ox the Sponsor atthe Wife Intemational Lid. aquatic toxicology facility 1 iPnrEotaescttoionn,AMgaernyclyanSde.iTeshe8s5t0udEycvoilolglibcoalpeErfffeocrtmseTdebsatsGeudidoenlipnreosceOdPurPeTsSiNntuhmebUeSrS8.30E.n5v4ir0o0n(m1e)ntaanld i OwoErCkDpeGrufioderlmiendae tfoWriTledsltiifnegoInftCemhaetmiiocnaallsL,i2d0.1a:ndAlagac,opGyroofwtthheIfnihniablitrieopnorTtewsitl(l2)b.efRialweddbaytaprfoorjeacltl 1 umber in archives located on the Wildlife Intemational Ltd. it or at an atemative locattiooben. speintcheiina frepoirt. || "Thepurposeoftisstudy istodetermiPnUetRhePtOoxSicEity of estsubstance othefreshwatergreen un alga,Selenastrum capricornutum, during a 96-hour exposure period. i "Thegroenalga,SelenasinuEmcXapPrEicRorImMutEuNm,TwAilLlbDeEcxSpIosGedNto ageometricseriesofat leastfive {estconcentrationsand a egative (culemedium)controlfor 96hours. Targetconcentrawtiilolnnost || exceed100 mp/L orthesolubility limitofthetestsubstanceinwater. Generthaelnolmiyna,l concentration ofcachtest substan usodinthedefinitive tetvillbeatleast S0%ofthenexthigher a `reament,unlessinformation conosminth coneentrtion-cffoctcurveindicates thatadiffrentdilution factorwouldbemoreappropriate. 1 1 Tes solutions vil be inoculated with 10,000 cclsfmL. Three "biological" replicates per experimentalgroupvil beprepare forevaluatingcelldensities.Oneormoreadditonal "analytical" replicateswillbeincuded thetest needed, oprovide est solutionforconcetrationverification onDay3oftheexposure.Anabioticreplicatsot thehighestconcentrationvill be included nthetest a andvillbe sampledon Day 3and Day4.Inordertocontrolbis,tepositionoftheflaskswillbe detrminedbyindiscriminatedrawdiyduringth exposureperiod. Noothe potesonurctesiofabials i `areexpectedtoaffecttheresultsofthestudy. a "Theresponseofthealgaewillbemeasuredintems ofceldeasity,biomassexpressedas area undethegrowthcurve,andgrowth te.AnECS0(ic,th theoretical est concentrationthatproduces. a a 50% reductioninthemeasured parameter)valueforcell deasitywillbecalculatedforcach 24hour interval. EC10,5050 andECv9al0u forcl deity,ity,bibiomes (50) aodgow rie GOwillbe 000 a PROTOCOLNO. 454/110998/SEL-S6H1/SUB454 3MLABREQUESNOT.U2723 a MW WiLoLirE INTERNATIONAL LTD. un oun calculated, (NOAEC), if possible,atthe 72and 96 hour intervals. Theno which sthe highest test concenttrhaattiniduocens observed no adverse adev ffece tconr cens trate ion inhibitoryeffecton growth, u wrielslubletsdane d tt he dre oeslea-r trievesm tpoonci saechpn patatree armne.d teArtatthe7e2nadndo9f6thheou9r6s-hboausreedxuppoosnuervea,laulagtiistoantoicfetfhfeecsttsatwiisltlicbael differefnrotmialagitciedadl effectsinthosetreatmentswhich aremaximally inhibited. MATERANDIMEATHLODSS ou inti Informationonthe characterizationof test,controlorreferencesubstancesisrequiredby Good Laboratory Practice Standards (GLP)."The Sponsor isresponsible for providing WildlifeInternational |] Ltd writtenverificationthatthetestsubstancehasbeencharacterizedaccordingto GLPspriortoitsuse inthestudy. IFwrittenverificationof GLP test substancecharacterizationisnotprovidedtoWildlife ou Intemational Lid.,itwillbenotedinthecompliancestatementofthefinalreport.The attachedform IDENTIFICATIOOFN TEST SUBSTANCE BY SPONSOR (Appendix I) is to be used to provide. mm information necfe ors GLPscoa mplr iany ce. A "The Sponsori responsiblefor ll informationrelated to thetest substance andagrees to accept anyunusedtestsubstanceand/or testsubstancecontainersremainingaftheend of thestudy. PrepaofrTeasttSoliutoionns: ThetestsubstanwcilelbeadminitosSteleenrasetrduminanaqueous `medium.Thisroute of administrationwasselectedbecauseit epreseaisthemost likely routeofexposuretoalgae,whichexists. inaquaticenvironments. Testsolutionswillbepreparedbydilutingoneormorestocksolutionswithalgalculturemedium toachievethetargetconcentrations. `Stocks will be preparedin algal culturemedium. Allweights, volumesanddilutions used to preparethetestsolutionsw.illbedocumentedintherawdata. TestOrganism `The fres greehnaw lga,aSelt enae strr um capricwoillrbenusueditn tuhismte, st. Thisspecies. isrepresentativeofanimportantgroupof algacand wasselected foruseinthetetbasedupon pastuse andeaseofhandlinginthe laboratory. Stock cultures, obtained from theCulture Collection ofAlgae. atthe UniversityofTexasatAustinor anothersupplier ilbe maintainedinculturemedium at Wildlife International Lid.for a minimum oftwoweeks priorto use in atoxicitytest. Algac usedin toxicity tests 000669 PROTOCOL NO.: 454/110998/SEL-96H1/SUB454 3MLAB REQUEST NO. U2723 | [Ml WILDLIFE INTERNATIONAL to. un = om willbe inexponentialgrowthphase,whichisdefinedastheperiodofgrowthwhenalgalcelsarc divatiacdonsitanntrtge. |:| Justpriortobeginnitnhge test,aninoculumofthestockculturewillbeprepsoathratecadch milliliterof inoculumcontainsenoughoels to providean ital cell density ofapproximately 10,000 ou celinleac/hrepmlicLate om CmCuletutremnediumpreparedsecordingto WldifeIntemational Ltd. Standard Operating Procedures willbeused asdilutionwater.Theconcentofrthaectomipoonenntss inthe medium ar presentiend | Table 1 (3). Stockmutientsolutionsvil bepreparedbyaddingreagent-gradechemicalsto Wildlife International Led.well waterpurifiedby reverse-osmosis. Appropriate volumes ofthestocknutrient om solutionsvillthenbodilutedwithpurifiedwellwatertopreparethemedium."Themedwiillbue fimlter sterilized(02 amorsutoslpraiovrteodus)e.Thefinal pHofthemediumshouldbe7.5.4.1. Analy- o seswill beperformedatleas once annuallytodetermine theconcentrationsof selectedorganicand inorganicconstituents ofthewellwate andresultsofteanalyseswillbesummarizedinthe inal report. ou Specifications for acceptable levels of contaminants have not been established for culture `medium.Howes,ther ar novel ofcontaminantsreasonablyexpectedtobepreseatinthe medium ol thatareconsideredtointerferewiththepurposeorconductofthestudy. HH TestApparatus Test chambers will be sterile, 250-mL polycarbonate Erlenmeyer flasks plugged vith foam stoppers. Eachtestchamberwillhold 100mLoftestsolution.Testchawilm lbeb indie scrir minas tely mn positionedon amechanicalshakertablein anenvironmentalchamberandvillbeshakencontinuously atapproximately 100 rpm. Test chambers wibellabelled with theprojectnumber, testconcentration, oH andreplicate `EnvironmentalConditions ol "Test flasks illbe eldat24 +2Cundercontinuousfluorescentlighting (c..colwhitelight tubes)atanintensityof approxima4t30e0ly 10% lux.Lightintensity willbemeasuredatfive ol locationsontheshakertabledailyduringthetest. Temwpillbeemerasuaredttwiceudalryinethe environmental chamber usinga liquid-in-glass thermometer. nm 000570 oH PROTOCOLNO.: 454/110998/SEL-96H1/SUB4S4 3MLAB REQUESNOT.U2723 WILDLIFE INTERNATIONAL LTD. -6- "ThepHofcachtreatmentan thecontrolwillbemeasureda estinitiationandterminationusing aFisherAccumetModel 915pHmeterorequivalent. Samples willbecolflromethecbattchoeftdest solutionpreparedat est nition fo cachtreatmentandcontrolgroupforthemeasuremoefpnHt. At testtermipHnwialltbemieaosurned,in potoestlsoelutdion samples colfrolmtehethcreetrepleicatdes ofcach treaandtconmtreolgnroutp. `BiologicalMeasurements `Celldensitieswillbemonitoredduringthetestbyconductingcellcountsusing 8 hemacytometer and amicroscope.Onesamplevillbecollectedfromeachreplicateofth treatmentandcontrolgroups at approximately 24hourintervalsduringtheexposureperiod. The sampleswillbe evaluated immediately. Each samplewillbedilutedusinganelectrolytesolution (Isoton),asneeded, tomaintain `countingaccuracy.Thecelldensityofthesamplewillbecalculatedbasedonthemeannumberofcells : pergrid. Samplesoftestsolutionswillbecollectedfromeachreplicatepertreatmentandcontrolgroup attheendofthetest.Eachreplicate samplevillbeexaminedmicroscopicallyforatypicalcell `morphology(eg.changesinshape,sizeorcolor). Growthofcellintheflasksalsowill beassessed foraggregationsorflocculation ofcelsandadherenceofthecllstothetestchamber. Attheendofthetest, algistatieffects,whichresultintheinhibitionofcelgrowth,willbe differentiated from algicidal effets, which result in the deathofcells. Aliquots (0.5 mL) of test solutionswillbetakenfromcach replicate testchamber where growthis maximally inhibited. Maximallyinhibitedtreatmentsar thoseinwhich itcannotbevisuallydeterminediflvealgalcellsare preseat (eg. absenceofcolortothetestsolution).Thesealiquotswillbecombinedanddilutedwith algalmedium to aconcentrationofthetestsubstancethattheoreticallyshouldnoteffectgrowth. A negativecontolwillbeprepare bydilutinga0.5Laliquotfromonenegativecontrolreplicateto 100 `mLwithalgal medium.Growth ofthesesubcultureswillbemonitoredforup to 9daystodetermine whetherinhibitionofgrowth observedduringthetest ireversible. Samplesvil becollcftorceedll countsat recoveayphassinitiation,terminationandatapproximately3-dayintervalsbetweeninitiation andtermination. Therecoveryphasemaybeterminatedoncealgalgrowthissulfcenttoindicatethat thealgalcells havefully recoveredfrom effetsductothetestsubstance.Thiswillbedetermined through visualexaminationoftherecoverytest solutions, PROTOCONOL.: 454/110998/SEL-96H1/SUBA454 000671 3MLABREQUENSOT. U2723 1MWioLFe INTERNATIONALLO. . . 1 substan`cSeamcponlceesontfratthieonesx.poDsauyre0soslaumtpiloensswwiillllbbeectoalkleeacfterdoomneaDcahysbat0c,h3oafntedst4asnolduatnioanlpyrzieodrfoo ttheesitr 1 distributionamongthereplicateestchambers.Day 3sampleswillbecollected romtheextrareplicate est chamber(s) included in the test to provide sample for that analysis and rom the abiotic replicates. |] 1 more than one replicate is included for the Day 3 sample analysis, then the solutions from cach replicatewillbcompositedtoprovid thesampleforthat treatment. Day 4sampleswillbecomposited ul solutionsfromthethree replicatesremainingatthe endofthetest 1 SamplescollectedonDays 3and 4 maybecentrifugedorfilteredto removealgal cellspriorto apnaolyslis.ypSarmpoolreppsoylwyilleltehbyenleanenealbyzoetd )imamneddsitaoterleyduonrtipllaacneadlyizneda.n appropriate The sample storage scheme ciosnstuaimnmearr(icz.egd, i below: PROPeOSEr D NUm MBERS OF VERIFICATION SAMePLtES Control | i Solvent Control (ifneeded) l Level 1-LowConsentration a Level2 Level 3 | a Levels I a |LLovel 5-HighConcentration L111 1 a "Theaboveumberofsamples representthosecollectedfromthetestanddono includequality control (QC) stmples such as marx blanks and fortifications prepared and analyzed during the i analytical chemistry phaseofthestudy. a 000672 a PROTOCOL NO.: 454/110998/SEL-S6HI/SUB4S4 3MLAB REQUEST NO, U2723 [Ell WILDLIFE INTERNATIONAL Lm. | _8- AnalyticalChemistry Chemicalanalysisofthesampleswillbeperformbeyd WildlifeInternationalLtd. The analytical `method used will be based upon methodology provided by the Sponsor and identified in Appendix IL. Modificationsmade tothe analyticalmethodwillbe documenitntehde rawdataanddescriibntehde final report. StatisticalAnalyses Bioxnassexpressedas areaunderthegrow curvewillbocalculated orthetreatmentandcontrol groups using the following formule: A= (ONAND INRE ) HNNNI) Where: "AN=,= MArcaeundaerntuhmsebgersuoowftchrcclusr/veem.L adtt, NN;, ==MMeeaassuurreedd nnuummbbeerrooffcceelllsl/mmLL aatttt, 'N, =Measurednumber of cells/mLatt, : t, = Timeoffirstmeasurementafterbeginningoftest(hours) 1, =Timeofsecondmeasurementafterbeginningof test(hours) t, =Time of nthmeasurementafterbeginning oftest(hours) Growthrates(x) willbecalculated forthe treatmentandcontrol groups usingthe following formula: pm --_IN, InN, tb N1,==AMveearsaugreedspnecuimfbicergorfocwethllrsat/emL att, N, = Measured mumberofcelisfmLat to=Time ofbegionftn esti(hn ourgs) t, =Timeofnthmeasurementafterbeginningoftest(hours) PROTOCONOL.: 454/110998/SEL-96H1/SUB454 000673 3MLAB REQUEST NO. U2723 1 1 = fl WILDLIFE INTERNATIONAL LTO A Percent inhibition will be calculated for each treatment group based upon mean cell density, n `biomass and growth rate using the: following formula: ii `Percent Inhibition =_ `MeRaens`pCMooennatsnreCooln-trMoelaRRneessTpprooenanstsmeeent X 100 EC values will be determined, when possible, using. linear interpolation or other suitable i techniques with treatment response (i. ocll densities, biomass and growth rate) and exposure u concentration dataforeach24-hourintervalofthetest. || {hedoseA-noresopbosnesrevepdaattdevmerasnedeftfhectrceosncuesnotfratthieosnta(tNisOtAicEalCa)nawliylslibsuessienlgectienddbiavisdeudalornepalinceavtaelvuaaltuicosnooff the cell density, biomass a he treatment groups will nd growth rate be identified . Stat using istically analysis significant d of variance ifferences b (ANOVA) etween the and a test control and to compere Mm treatmentmean responsestothecontrol response(. cg , Dunnett's test or Bonferroni'st-test).Datawill om boassessedfornormalityandhomogeneityofvariancesprior toperforintheANOVA. Transform- om taisoonlsvweinltlcboenutsreodlitocuosrerdeicntaadndyictoinodnittoiotnhoefnengoant-invoercmoanltirtoylo,rtuhneeirqrueaslpeornosersvwariilalnbceecs,omifppaosrseidbules.inig `Student's t-test. Datafrom thetwocontrolgroupswillbepooledfortreatment levealnalysesifno statisticaldifferencesexist.Otherwise, allcomparisonswillbemadeto thesolventcontrolgroup. Statisial comparisonsfor ANOVAsnd hecomparisonofmean responsesvill be cared outusing TOXSTAT V3.5 software (4) or equivalent. REC TOBOEMR AIND TAIS NED RecordstobemaintainedfordatageneratedatWildlifeInternational Ltd.vil include,butnt be limited to: 1 Copy of signed protocol. 2. Identificationandcharacterization of thetest substance,ifprovidedby Sponsor. 4 Souseofalgae. 3. Datesofinitiation andterminoaftthietoesnt. 000674 5. Culture conditions. PROTOCOL NO.: 454/110998/SEL-96H1/SUB45 3M LAB REQUEST NO. U2723 8 Jl WILDLIFE INTERNATIONAL LTD a -10- i ou ["] ou u || om ou ou Mm mn 6. Growthmeasurements. 7. Calculationandpreparationoftestconcentrations. 8. Observations. measurements 9. The methods usedto analyzetestsubstanceconcentrationsand theresultsofanalytical 10. Statistical calculations. 11. Testconditionsandphysical/chemicalmeasurements. 12. Copyof finalreport. FINALREPORT Afinalreportoftheresultsof thestudy villbepreparedbyWildlifeIntemational Ltd.Thereport. willinclude, but notbe limited tothe following,whenapplicable: 1. Na andm addre essofthefacility perforthmesitundyg. 2. `Datesupon which thestudywasinitiatedandcompleted, andthedefinitive experimentalstartand 3. terminationdates. . Astatementof compliancesignedbytheStudyDirectoraddressinganyexceptionsto Good `LaboratoryPractice Standards. 4. Objectivesandprocedures,asstatedinthe approvedprotocol,includingallchanges tothe protocol. 5. Thetestsubstanceidentification including name,chemical abstract numberor code number, strength,purity,composition,and otherinformation providedbytheSponsor. 6. Stabilityandsolubilityofthetestsubstance under theconditionsofadministration,ifprovided. `bytheSponsor. 7. A descriptionofthe methods usedto conductthetest. 8. Adescorf tihetpesttorgianoismns, incluthde siounrcge, scineamen,atgeoir lfifesitagce, light intaendnphsotoipetrioyd. 9. Adescriptionofthepreparationof thetestsolutions. 10. Themethodsusedtoallocateorganismstotestchambers andbegin thetest,the number of organismsandchamberspertreatment,andthedurationofthetest. 11. A descriptionofcircumstancesthatmayhaveaffectedthequalityorintegrityofthedata. 000675 PROTOCNOOL.: 454/110998/SEL-96H1/SUB454 3MLABREQUENSOT. U2723 1 J WILDLIFE INTERNATIONAL L1D. 1 -11- 1 12. ThonameoftheStdDirectorandthe namesof otherscieatists,professaindosnupaerlvisso,ry personnelinvolvedin thestudy. a 13. A description ofthe transformations, calculations, and operations performed on the data, a summaryan analysisofthe biologicaldata ndanalyticalchemistrydata,andastatement ofthe a conclusionsdrawfrom tahnalyses. Agraphplottingtheconcentrerspaontseicuorvne. 14. Statisticalmethodsusedtoevaluat thedata. a 15. Thesignedanddatedreportsofeach ofthe individual scientistsorother professionals involved inthe study. n 16. 17. TAhsetaltoecmaetniotpnwrheeparreerdabwydtahteaQaunadliftiynAalsrseuproartncareeUtotbleissttionrgetdh.edatesthastudyinspectionsand a itsweremadeand hedates ofanyfindingsreportedtothe StudyDirectorand Management. 18. Ifitisnecessary tomakecomostionsoradditionsto afinalreportafer ithasbeenaccepted,such au changeswillbemadeintheform ofanamendmentissuedbytheStudyDirector. Theamendment - willlealy identifythepat oftefinal reportthatisbeingamendedandthereasonsforthe om amendment,andvillbe signedbythe StudyDirector ou CHANOFGPRIOTNOCGOL Plannedchangestotheprotocolwill be in the formofwritenamendmentssignedbytheStudy Hl DirectorandtheSponsar'sRepresentative.Amendmentsvillbeconsideredaspartoftheprotocol and illbeattache to theinlprotocol.Anyotherchangeswillbe i theformofwritendeviationssigned a bythe StudyDirectorandfledwiththerawdata. Allchangestotheprotocol illbeindicatedinthe = final report. GOODLABORATORY PRACTICES H "ThisstudywillbeconductedinaccordancewithGoodLaboratoryPracticeStandardsforEPA (40 CFR Part 160 andlor Part 792); OECDPrinciplesofGoodLaboratoryPractice (OCDE/GD (92) 32, Environment Monograph No. 45); and Japen MAFF (59 NohSan, Notification No. 3850, Agricultural Production Bureau), Each study conducted by Wildlife Intemational Lud. is routinely examined by the Wilde Intemational Lid. Quality Assurance Unit for complisncs with Good Laborstory racic,StandardOperating Proceduresandthespecifiedprotocol. Astatemenotf PROTOCONOL; 454/110998/SEL-96H1/SUB4S4 3M LAB REQUEST NO, U2723 000676 WILDLIFE INTERNATIONAL LTD. -12compliance with Good Laboratory Practices vill be preparedfo all portionsofthe study conducted by Wildife International Ltd. The Sponsor will be responsible for compliance with Good Laboratory Practice for procedures performbeyd other laboratories (e.g. residue analyses or pathology). Raw data forallworkperformedatWildifeInternationalLid.and acopyofthefinalreportwillbe filedbyproject number in archiveslocatedon the Wildlife International Ltd. site of at an altemative location to be: specified in the final report PROTOCOL NO.: 454/110998/SEL-96H1/SUB4S4 000677 3MLAB REQUEST NO. U2723 J WILDLIFE INTERNATIONAL LTD. 1 -13- 1 RERINCES 1 1 US. Environmental ProtectionAgency. 1996. Series 850-EcologicalEffects Test Guidelines (drafi), OPPTS Number 850.5400: Algal Toxicity, Tiers I and IL 1 2 OECD Guideline for TesoftChi emincalgs. 1984. 201: Alga, Growth Inhibition Test. 3 ASTM Standard Guide 1218-90E. 1990. StandardGuide for Conducting Static 96-Hour 1 Toxicity Tests with Microalgae. 4 West, Inc. and D.D. Gulley. 19%. TOXSTATRelease 3.5. Western EcoSystems Technology, || Inc. Cheyenne, Wyoming. a 000678 a PROTOCOLNO.: 454/110398/SEL-96H1/SUB4S4 3MLAB REQUEST NO. U2723 i WILDLIFE INTERNATIONAL LTD. a 14 a TABLE FRESHWATER ALGAL MEDIUM CONSTITUENTS ou Component Nominal Concentration n MCEaCCLl62HH,,O00 4142016 mmgg MHa,CBl0o,4H,0 00.4118656 mmg/gL ou FeZCCl,i6H,0 302.81598 gmgl/L i CNoeC,lM6oHO,,20H,0 7124268 uugg CNau,CELD2THA,20H,0 00031020 mugl i MNgaSNOO,,7H,0 21545700 mmegl "] KNaHHPCOO,, 1044 mglL 1500 mpl "The pHofthemediumwillbeadjusted,asnecessary,t07.5%0.1using0.1 ua NNaoOr1H0% HCL ou 000679 i| PROTOCONOL.: 454/110998/SEL-96H1/SUB454 3M LABREQUEST NO.U2723 J WILDLIFE INTERNATIONAL LTO. 1 -15- 1 Ju IDENTl IFICATION OFi ATPEPSETNSDUIBXSTAa NCE BYaSPbOaNn SOR a I- TobeCompletebdy Sponsor I Test Substance dent (nametobeused nthereport): E(QPS erfluoSulrfonoicAocidsPottasasiunmSaelt 1 Reference Standard (f applicable): AnaIlnytteircnaall SSttaannddasr:d_NP1.1e.A2.r2F1fHHlHuorooSculftonaicAncied 1 Test Substance SampleCodeorBatch Number:_ Lot 217 Test Substance Purity (% Active Ingredient): _989 Expiration Dot: 2008 1 IL Test Substance Characterization Havethe identity,bstyrdefing D ietytanudcbompaositatnidoirnoernforthoaecrcShtaarnadcatrerdibseticcns 1 Hetcrminedprior tisuseinthisstudyin accordancewith GLPStandards? YesNo X_ IL Test Substance Storage Conditions i _PA l_easem indicb atetheirece omment dedstr orageo condio tionsamtWilt dlifeIe ntemam tionp alLide . rsee i HHaes tehesa tabilityofthe testeseuwabl sCuLntFdeSrautahnnedsaecrsdtseo]rage condifions YesN_o_X__ 1 O-- ther p-- ertinen-- t steabi-- elite y inf-- oe rmatio-- ns ---------------------- 1 IV. TestConceatrations: _X_Adbajsuesdtupesotnctohnecpeunrittrya(t%it)ogoniv1e0n0%ebnoiv.e. Dao1noTtesdttshte mastetricaolnAeSsmISp.ionto 100% |] V. Toxicity Information: Mammalian: ~~ RatLDS025lmghke MouseLDSO NA i Aquatic: InvertebrE ateToxicZ ity (BC/LCS0) 2 Fish Toxic.ity (LC50) Ha Diphniamagna: Somg/l Fathead Minnow, 38mg/l Other Toxicity Information (including findingsofchronic and subchronic tests): ul HemMDS 000680 PROTOCOLNO: 454/110998/SEL-96H1/SUB4S4 3MLAB REQUEST NO, U2723 1 1 WILDLIFE INTERNATIONAL LTD. 1 -16- APPENDIX I 1 Ansytical Method to be Provided by Sponsor I 1 I I 1 1 I 3 I I I I I 1 I 000681 [1 PROTOCOL NO.: 454/110998/SEL-96H/SUB4S4 MLAB REQUEST NO. U2723