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cl AR26-0187 OES -Y PROTOCOL PFOS: A96-HOURTOXICITY TEST `WITH THE FRESHWATER DIATOM (Navicula pelliculosa) U.S. Environmental Protection Agency `Series 850 - Ecological Effects Test Guidelines `OPPTS Number 850.5400 - ' `3MLabRequesNot.U2723 `Submitttedo : 3M Corporation Environmental Laboratory 935 Bush Avenue: St. Paul, Minnesota 55106 Wildlife International, Ltd. \ 8598 Commerce Drive : Easton, Maryland 21601 (410) 822-8600 September 17, 1999 04498 WILDLIFE INTERNATIONAL, LTD 2. PFOS: A96-HOUR TOXICITY TEST WITH THEFRESHWATER DIATOM (Vavicula pelliculosa) `SPONSOR: `SPONSOR'SREPRESENTATIVE: IESTNGFACLITY: STUDYDIRECTOR: LABORATORYMANAGEMENT: 3MCorporation `Environmental Laboratory 935 Bush Avenue St. Paul, Minnesota 55106 RochellRe Robidean Wild InternatioLind,. 8598 Commerce Drive. `Easton, Maryland21601 SarsDrotiar Cary Stbasland `Senior Aquatic Biologist HE thief HDeniryrOe.oKfcrAutqeugoaetrri,cPTAoDx.icology & Non-TargetPlants FOR LABORATORY USE ONLY Proposed Dates: ' `Experimental `Experimental Start Date: ProjoctNo: _OY4A-/12 `TerminationDate: . `Test Concentrations: --- "TestSubstance No.: `ReferenceSubstanceNo.(ifapplicable): PROTOCOL APPROVAL DEpo H STUDYDIRECTOR x4 LABOI RV, \GEMENT =S ,a A Fm Y . SPONSORS REPRESENTATIVE = PROTOCOLNO: 454/091799/NAVI6/SUB4S4 fhe DATE 1/8foo DATE DA) 04499 3MLAB REQUESTNO.U2723 WILDLIFE INTERNATIONAL, LTD 3. INTRODUCTION `WildlifeIntemational,Ltd.willconduct afive-daytoxicitytestwiththefreshwaterdiatom,Navicula pelliculosa,fortheSponsor attheWildlife International, Ltd. aquatictoxicologyfacility in Baston, `Maryland.Thestudywillbe performedbasedonproceduresintheU.S.EnvironmentalProtectionAgency `Series 850 -EcologicalEffectsTestGuidelinesOPPTS Number850.5400(1). Rawdataforallwork performedatWildlifeInternational,Ltd.and acopyof thefinalreportwillbefiled byprojectnumberin archiveslocatedontheWildlifeInternational,Lud.sit,oratanaltemativelocation to be specifiedinthefinal report. "= PURPOSE "Thepurposeofthisstudy istodeterminethetoxicity ofPerfluorooctane SulfonicAcid,Potassium `Salt(hereafterreferred to as PFOS) to the freshwaterdiatom, Navicula pelliculosa. EXPERIMENTALDESIGN : `Thefreshwaterdiatom, Naviculapelliculosa,willbeexposed to ageometricseriesofsixtest `concentrations and anegative (culturemedium)controlfor 96 Bours.Targetconcentwrilalntotieoxcneesd 100mg/Lorthesolubilitylimitofthetestsubstanceinwater. Generally,thenominalconcentraotfciaocnh testsubstanceusedinthe definitivetestwil beatleast 50%ofthenexthighertreatment,unlessinformation `concerning the concentration-effectcurve indicates that adifferentdilutionfactor would be more appropriate. Testsolutions willbeinoculatedwith 10,000celsfmL.Three"biorleploicatgespircexpaerilmen"tal groupwillbepreparedforevaluatingcelldensities.Oneormoreadditional "analytical" replicates willbe includedin the test, as needed, to provide test solution forconcentration verification onDay 3of the. exposure. Anabioticreplicateatthe highestconcentrationwillbeincludedinthetestandwillbe sampled onDay 3andDay4.Inordertocontrolbias,thepositionoftheflaskswillbedeterminedbyindiscriminate drawdailyduringthe exposureperiod.Nootherpotentialsources ofbiasare expectedtoaffecttheresults ofthestudy. `Theresponseofthealgae willbemeasuredintermsofcelldensity,biomassexpressedasarea under thegrowthcurve,andgrowthrate. AnECS0(i.c.,thetheoreticaltestconcentrationthatproduces a 50% `reductioninthemeasured parameter)valueforcelldensity willbe calculatedforeach24 hourinterval. ECI0,EC50 and EC90 valuesfor celldensity, biomass (EyC)and growthrate (E.C) willbe calculated,if 04500 PROTOCOLNO.: 454/091799/NAV96/SUB454 3MLABREQUENSOT. U2723 WILDLIFE INTERNATIONAL, LTD 4 possible,atthe72 and96 hourintervals.Thenoobservedadverseeffectconcentration (NOAEC),which isthe highesttestconcentrationthatinducesnoadverseinhibitoryeffectongrowth, willbedetermined relativeto cachparameterat72and 96hoursbaseduponevaluationofthestatisticalresultsandthe dose- responsepattem.Attheendofthe96-hourexposure, algistaticeffectswillbe differentiatedfromalgicidal + `effectsinthosetreatmentswhicharemaximally inhibited. TestSubstance ~ MATEARNDIMAETHLODSS Informationonthecharacterization oftest,controlorreferencesubstancesisrequiredbyGood LaboratoryPracticeStandards (GLP). TheSponsorisresponsibleforproviding WildlifeInternational,Ltd. writtenverificationthatthe testsubstancehasbeen characterizedaccordingtoGLPspriortoifsuse the `study.Tfwrittenverificationof GLPtestsubstancecharacterizationisnotprovidedto WildlifeInternational, Ltd,itwillbenotedinthecompliancestatementofthe finalreport.TheattachedformIDENTIFICATION OFTEST SUBSTANCE BYSPONSOR (AppendixI)istobeusedtoprovideinformationnecessaryfor GLPcompliance. "TheSponsorisrespofornalslii nfobrmaltieonrelatedtothetestsubstanceandagreestoaccept any unusedtest substanceand/ortestsubstancecontainers remainingattheendofthestudy. Fest Seton Brsgueals "ThedesiredconcentrationsofPFOSwillbeobtainedbypreparing asinglestocksolutioninmedium `anddilutingthe appropriatevolumeofstocksolutionwithmedium.Thetestsolutionsmayalsobeprepared `using secondary dilutionsofthe primary stock, based upontheconcentration desired. Thetestsubstancewillbeadministeredto thetestorganisminalgal medium. Thisrouteof administration wasselectedbecauseitrepreseatsthemostlikelyrout ofexposuretoalgae,whichexist suspineawanterdcoelumdn. `TestOrganism Thetestspecieswillbethefreshwaterdiatom,Naviculapelliculosa.Thisspeis creprieseentatsive ofanimportantgroupofalgaeandwasselectedforuseinthetestbaseduponpastuseand caseofhandling. inthelaboratory. Stockcultures,obtainedfromtheCultureCollectionofAlgaeattheUniversityofTexas PROTOCOL NO: 454/091799/NAV96/SUB454 04501 3MLABREQUEST NO. U2723 WILDLIFE INTERNATIONAL, LTD ose atAustin oranothersupplier,willbemaintainedin culturemediumat Wildlife International,Ltd.for a `minimumoftwoweekspriortousein atoxicitytest.Diatoms usedintoxicitytestswillbe inexponeatial `growthphase,whichisdefinedastheperiodofgrowthwhenalgal celsaredividingat aconstantrate. Justpricrtobeginningthetest,aninoculumofthestockculturewillbepreparedsothateachmilliliter ofinoculumcontainsenougheelstoprovidean italclldensityofspproximately 10,000cells.incach replicate. - Culture Mediom CulturemediumpreparedaccordingtoWildlifeInternational,Ltd. StandardOperatingProcedures `willbe usedasdilutwiatoenr.Theconcentrations ofthecomponentsinthemediumare presentedin Table 1(2). Stocknutrientsolutionswillbepreparedbyadding reagent-grade orbetterchemicalstoWildlife International,Ltd.wellwaterpurifiedbyreverse-osmosis. Appr volo umespofr thei stoa ck nt utrie ent `solutionswillthenbe diluted with purified wellwaterto preparethe medium. Themed wililbeufilm ter `sterilized (0.22jum)orautoclavedpriortouse.Analyseswillbeperformedatleastonceannuallyto determinetheconcentrationsofslectedorganic andinorganicconstituentsofthewellwaterand resultsof themostrecent GLP compliant analyseswillbesummarizedinthefinalreport. `Specificationsforacceptablelevelsof contaminantshavenotbeenestablishedforculturemedium. However, therearenolevels of contaminants reasonablyexpectedtobepresentinthemediumthatare `consideredtointerferewiththepurposeorconductofthestudy. TestApporats `Test chambers willbe sterile, 250-mLpolycarbonateErlenmeyerflaskspluggedwithfoamstoppers andcont100amLiofntesitsonlutigon. The testchamberswillbeindiscripmosiintiaontedeolnay `mechanicalshaker tableinanenvironmentalchamberandwillbeshakencontinuously at approximately 100 rpm. Testchamberswillbe Labelledwiththe project number,test concentrationand replicate. . Con `Test flaskswillbe heldat24 +2Cundercontinuouscool-whitefluorescentlightingatanintensity of4310 0% l0 ux.Lightintensitywillbemeasuredat fivelocationssurroundingthetestflaosnDkays0 004502 PROTOCOLNO.: 454/091799/NAV96/SUB4S4 3MLABREQUENSOT. U2723 ~ Hs W--I_L--DLIFE INTERe NATIOy NAL,e LD -6- ofthetest. Temperaturewillbemeasuredtwicedailyin a containerofwateradjacenttothetestflasksinthe cavironmentalchamberusing acalibrated,hand-heldmercurythermometer. . `ThepH ofcachtreatmentandcontrolgroupwillbemeasuredattetinition andterminatingusing. ~ aFisherAccumet Model 915pHmetero equivalent. SafmorppHmelasuerecseatattetinitiavtiilobne collectedfromtheindividualbatchesoftestsolutionpreparedforcachtreatmentand controlgroup.Attest termination,pHwillbemeasuredinpooled samplesoftestsolution collectedfrom cachofthethresreplicates ofeach respectivetreatmentandcontrolgroup. J `Celldensitieswillbemonitodurreindgthetes byconductingcllcountsusingabemacytometaendr amicroscope. Onesamplewillbecollectedfromeachreplicateofthetreatmentandcontrolgroupsat approximate 24-hourintervalsduringtheexposureperiod.Thesampleswillbeevaluated immediatelyor willbeheldinthedark at approximately 4Cuntil cellcountscanbeperformed. Eachsamwilplbeldilueted usinganelectrolytesolution(1soton),asneeded,to maintaincounting accAusmarll aamocuntoyfe.ach samplevillbeloadedonto 8 hemacytometerandthetotal mumberofcellsin10gridswillbecounted. The celldensity ofthesamplewillbecalculatedbasedonthemean mumberof celspergrid. Microscopic examination ofalgaewillbemadetoassesschangesingrossmorphology. Algaewill . `beobservedtoassesschangesincel shape,cllcole,andagbregation (clumopfithnecgel)l. Observations. willbeusedtodeterminewhethertreatment.elated effcts includethosechanges ingrossmorphology. Saul . SamplesoftheexposuresolutionswillbecollectedonDays0,3and 4andanalyzedfo tetsubstance. `concentrations.Day 0sampleswillbetake fromeachbatchofestsolutionpriortotheirdistributionamong. thereplteistcchaambteres. Day 3samples willbecollectedfromtheextrareplicatetest chamber(s)included. inthetesttoprovidesampleforthatanalysisandfromtheabioti replicates.Ifmorethanonereplicates includedfortheDay 3 sampleanalysis,thenthesolutionsfromeachreplicatewillbecompositedto provide. thesafomrthp attrl eatme ent. Day 4sampleswillbecompossoiluttieondsfromthethreereplicates remaatthieenndoifthne tegst. PROTOCOLNO: 454/091799/NAVI6/SUBAS4 604503 3MLABREQUESNOT, U2723 wast WILDHLiIFeE NITNeTRENRaNAmTiIOONNAALL,,ULTBD 7. `Samplescollectedon Days 3and 4maybecentrifugedorfilteredtoremovealgalcelsprior to analysis. Sampleswillbeanalyzedimmediatelyorplacedinanappropriatestoragecontainer (e.g, `polypropylene or polyethylenebottle) and storeduntilanalyzed.`The sample scheme is summarizedbelow: [vco|cou o|iono s mows e | PROPOSED NUMBERS OF VERIFICATION SAMPLES Control SolveatControl(fnccdd) Level1-LowConcentration Level2 Leve3l Leve4l Level5 (| ws Level 6-HighConcentration ) `The abovenumbersofsamplesrepresentthosecollectedfrom thetestanddonotincludequality `control (QC)samplessuchasmatrixblanksandfortificationspreparedandanalyzedduringtheanalytical `chephmasieosftthesrtuydy. ge Cn Chemical analysis of the samples willbeperformedbyWildlife Intemational Ltd.`Theanalytical `method usedwill be based uponmethodology providedbythe Spoan ndis deno tifiredinAppendix IL. -- mea. . `Modificationsmade totheanalyticalmethodwillbe documentedintheraw dataand described inthefinal a Biomassexpressedas areaunderthegrowthcurvewillbecalculatedforth treatmentandcontrol roupsusingthe following formula: 04504 PROTOCOLNO.: 454/091799/NAV96/SUB4S4 3MLABREQUENSOT. U2723 TWHILDDULIrFEEIIMNeTRENRNAAITOINONAALLY, 210D, . ER A= (ONYX HNN NY 2th) + AHNar Ne2NV2te)) Where: AN==AMrecaasuunrdeedrnuthmebgerorwotfhcceulrsvfea.Latt, : NN;, ==MMeennaauummbssberoouuff cceerrllilssef/emmLLaaddtt,t; N,==TimMeofefirssmtummebsaesuorufemcerenltsaemfLeardtbte,ginningoftest(hours) ta==TTiimmesooffnSetchomnedamseuarseumreenmtaefnttearfbteergibnengiinngnoifngtoesftt(ehsotu(rBso)urs) Growthrates)willbecalculatedfothe treatment ndcontrolgroupsusingthefollowingformula: InN,InN re -- to 1N4 == AMvereagesapnecuimsfbiecgruroofwctrehlrsaietneLadtt, : Ntoo==TMimeeofbaemgasmibnenruooifftnceregtls(eihoauLrasd)t, t=Timeof thmeasurementafterbeginningoftest (hours) Pesocatinhibitionwillbecalculate forcachramentgroupbaseduponmeancel deasity,biomass: andgrowthrateusingthe followingformu: PerccotInhibition =M_eRaenspConose n-MetRaensrTproenoastemlent X 100 `MeanControlResponse ECvalues willbedetermined,wheapossible,usingincrinterpolation oothersuitabletechniques withtreameatresponse i.celldensitics,biomass an growth ate)and exposure onceatrationdatafor cach 24-intehrvalooftuetrest. oT "Ano observedadverseeffectconcentration(NOAEC)willbeseletedbasedon aevaluationofthe dose responsepattemandtheresults ofthestatisticalanalysisusing individualreplicatevaluesofthecel densitybioanmdgraowtsh raste. Statisticallysignificantdifferencesbetweenthecontrolan thetreat groupswillbeidentifiedusinganalysisofvariance (ANOVA)and atestto comparetreatmentmean PROTOCOL NO: 454/091799/NAVIG/SUBAS4 3MLABREQUESNOT.U2702304505 _ WILDLIFE INTERNATIONAL-- , LD . -9- responsestothecontrolresponse (c.g.Dunestest orBonferroni's tes).Datawillbeassessfeodr c`noorrrmeacliatnyaycnodnhdiotmioogneonefitoynofnovrarmiaalnicteysorpurinoertquoapleerrfroorrmvianrigatnhceesA,NiOfpVoAss.ibTler.Iafnassolfveonrtcwmoinlatlrbtoleiiussouensdetsod inadditiontothenegativecontrol,theirrespoaseswillbecomparedusingStudent' ttst. Datafromthe 0cnirolgroupswillbepooledfor treatment velanalysesif nostatisticaldifferencesexist.Otherwise, allcomparisonswillbemadeto th solve coutrolgroup. Statistical ommparisonsforthe ANOVAandthe comparisonofmeanresponseswillbecadoutusingTOXSTATV3.5software(4) orequivalent. `Records to bemaintainedfoR rdatE ageneC rTatOedO BaEt WMR iAldIliNfD eTIAntIeS NrnEatDional,Lid.willinclude, butnotbe limitedto: 1. Copyofsignedprotocol. 2. Identificationandcharacterizationofthetes substance,ifprovidedbySponsor. 3. Datesofinitiationandterminoafteitoesnt. : 4. Souccofalgae. 5. Cultureconditions. : 6. Growth measurements. 7. Calculationandpreparation of testconcentrations. 8. Observations. . ; 9. Ifappliable,themethodsusedtoanalyzetetsubstanceconcentrationsandtheresults of analytical measurements 1101.. STteastitsctoincdailtciaolnuslaatnidopnhsy.sicallchemicalmeasurements. | 12. Copyoffinalreport. Afinalreportof theresultsofthest[uFdyIwNiAlLlbReEprPeOpaRrTedby WildlifeInternational, Ltd.Thereport willinclude,but no belimitedto thefollowing,when applicable: 1. Nameandaddressofthefacilityperformingthestudy. PROTOCOLNO.: 454/091799/NAVSG/SUBAS4 04506 SMLABREQUESTNO.UZ723. W_I--LDLIFE INTERNATIONAL,aLo -10- - - 2. Datesonwhichthestudywasinitiatedandcompleted.Itisth responsibilityoftheSpoasorto providethefinaldatethatdata rorecordedforchemistrypathologyandlorsupportingevaluations thatmaybegenerateda otherIsboratoties. 3. Astatement ofcompliance signedbytheStudyDirectoraddressinganyexceptionstoGood LaboratoryPractice Standards. 4. Objectives andproceduresstatedintheapprovedprotocol,includinganychangesintheoriginal protocol " 5. Thetest substanceidetiiedbynan,chemicalabsract umberorcode number,strength,puriy, composition,andothercharacteristics povidedbytheSpousor. 6. Stabilityandsolubilityofthetestsubstancesundertheconditionsofadministration,ifprovidedby the Spoasor. 7. Adescriptionofthemethodsusedtoconductthetest 8. Adescriptionofth testsystem,includingthesourceofthe estorganismsandtherscientificname, 9: Adescriptionofthepreparation ofthetestsolutions,methods sedtoallocateorganist tothetest c-hambersandbeginthe est, numbersoforganismsandc hambers pertreatmeat,and duration ofthe 10. Adescriptionofcircumstancesthatmayhaveaffectedthequalityo itegrityofthedata. 11. ThenameoftheStudyDirectorandthenamesofotherscicatits,professionals,andsupervisory personnelinvolvedinthe study. 12. Adescriptionofthtransformations,calculations,o operationsperformedonthedats,8summary andanalysisofthebiologicaldata andanalyticalchemistrydata, and astatementoftheconclusions drawn fromtheseanalyses. 13. Statisticalmethodsemployedforanalyzingthedata. 14. Thesigoedanddatedreportsof achoftheindividualscientistsorotherprofessionalsinvolvedathe sud. . 15. Thelocationwhererawdataandfinal reportarotobestored. 16. AstatementpreparedbytheQualityAssuranceUilistingthedatestha styinspectionsandmits weremadeandth datsofanyfindingsreportedto the StudyDirectorandManagement. 17. Ifitisnecessarytomakecomectonsoradditionsto afinalreportaferithasbec acocpted,such `changesshallbemadeintheformofan amendmentissiedbythe Study Director. Theamendment PROTOCOLNO: 454/091799/NAVO6/SUBASS 3MLABREQUESTNO. 04507 U2723 _WI--LDLIFE INTERNATIONAL, 10 -- sahlatlerlactlieoan.rlAyimdeenadtimfeyntthsesphaarlltboefstihgeofeidnaalnrdedpaotretdtbhyattihesSbteuidnygDaimreecntdoer,dandthe reasonsfor the Plannedchangestothe CHANOFGPRIOTN OCG OL protocalwillbeinthe formofwritenamendmentssignedbythe Study DirectorandtheSpoasar'sRepresentative. Amendmeatswillbeconsideredasprtoftheprotocolandvill beatatotchefihnalpreotocdol. Anyotherchangeswillbe itheformofwritendeviationssignedbythe Study Directorandfledwiththe raw data.All changes otheprotocolwillbeindicatedinthe finalrepart. `GOOD LABORATORYPRACTICES `ThisstudywillbeconductedinaccordancewithGoodLaboratoryPracticeStandardsforEPA (40 `CFRPert 160and/or Prt792); OECDPrinciplesofGoodLaboratoryPractice (ENV/MC/CHEM(98) 17); aod JapanMAFF(59 NobSen, Notification No. 3850, Agricultural Production Bureau). Eachstudy `conductedby WildlifeIntemational,Ltd.isroutinelyexaminedbytheWildlife International,Ltd.Quality AssuranceUnitforcompliancewithGoodLaboratoryPractices, StandardOperatingProceduresandthe. specifiedprotocol. Astatementof compliancewith Good Laboratary Practiceswillbepreparedforall portionsofthestudy conductedby WildifeIntemational,Ltd. The Spwiollbn eressponsoibler for `compliancewithGoodLaboratoryPractices forproceduresperformedbyotherlaboratories (e.g.residue anaolrpyathsoleogys). RawdataforalworkperformedatWildlifeIntemational,Lid.and acopyofthe finalreportwillbefiledbyproject numberinarchiveslocatedon theWildlifeInternational,Lid site,orat an altemativelocationtobespecified in thefinalreport. PROTOCOL NO: 454/091799/NAV96/SUBAS4 04508 3MLABREQUEST NO. U2723 W-I_--LDLIFE INTERNATIONAL, LD 12- REFERENCES OOOO 1 US. Environmental ProtectionAgency. (draft), OPPTS Number 850.5400: Algal 199.Series 850- EcoloEgffiectcs aTelst `Toxicity, Tiers Iand IT. Guidelines 2 TAeSstTsMwiStht MicraoaGlnguaied d.Aem1a 2e1r8ir -c9a0d nE.Soc19i9e0t.ySftoarnTedsatridnGguainddeMfaotrerCioanldsu.c`tPihniglaSdtealtpihci9a6,-PHenonusryTluvxainciiat.y 3 CNoonrcbeenrtgr-aKtiinong,(ITC,J).Ap1p9r9o3.acAhL(iVneerasriIonnt2e.r0p).olUaStSi.onEMxevitrhoondmefnotraSluPbrloettehctailToonAxigceintcyy:,TEhnevIinrhciobmienttiaoln Research Laboratory, Duluth, Minnesota. 4 `WCehseyte,aInnec,.aWnyodmDi.nDg..Gulley. 1996. TOXSTATRelease3.5.`WesternEcoSystemsTechnology,Inc. : \ PROTOCOLNO.: 454/091799/NAV96/SUB4S4 04509 3MLABREQUEST NO. U2723 A WILDLIFE INTA ERNATIONAALy, LIDD ee-- BER TABLE 1 - FRESHWATERALGALMEDIUMWITHSILICA CONSTITUENTS --_-- Component _-- MgClr6r0 CaCle2H0 Nominal Concentration : 241460 mmLg H;BO; MaCls4H,0 ZnCl, 0.1856 mg/L. 0416 mg/L 328 gL FeCly6H0 0.1598 mg/L. CNoCelM#o6HO,20HO " CuCly2H,0 1428 gL 726 gL 0012 gL Na:EDTA2H,0 0.300 mg/L. MNgaSNOO;STHO 21545700 mmgg/tL KPO, 1.044 mg, - NNaasHCSOi,O9H0 2105000 mmg/gL NesSeby:SH0 0010 mg/L "ThepH ofthemedium wilbe adjusted,asnecessary,to7.5 0.1using 0.1 _'--N'_N--aOH or 10%HCL - A tm rem cern PROTOCOL NO.: 454/091799/NAV96/SUB454 04510 3MLABREQUENSOT. U2723 -- WILDLIFE INTE_ RNATIONAL, 10----y Sue APPENDIXT . DENTOIFTEFSTSCUBSATANTCEBIYSPOONSNOR TobeCompblySepotnsaor L RTeefsetrScuabcsetSauncnedIadrednti(tfy a(pnpalmiectaoblbee:usAneadliynttihcaelreSptoarntd)a:`rdF: ONS(APerfluorooctane SulfonicAcid PotassiumSalt TestSubstanceSampleCodoorBatchNuInmtbeerrna:l_St_aLnodatr2d1:_71,12.2HH HHPerfluorooctaneSulfonicAcid TestSubstancePurity(%ActiveIngredient): _ 98.9 I TestSubseCharctrizaicn ExpirationDate: _2008 SHp timoe yortsoi oongsBphtlsy nnmdoyeo posaiocnom coeee rrCdcFhrtSin ielsis?s Ye x Mo IL TestSubsStotragaeConndictioens Plas fit recommendedscragecodons aWide trata],Lid. | HR iste in ertt oecodon Yo J -- _-- SER IV. TestConeenttions: . I-- pr RE V. Tofxormation: ont 100% Memmalian: Aqui: RatLDSO 251mg/kg MouseLDSO_N/A InvertToxicityGOLCS0) FishTnicy(C50) : 226g Raith Trou: 1 A FT Ot Todicty Information ochingfing ofcrcsc sbetrni5c): x MN mat PROTOCOLNO: 454/091799/NAVS6/SUBASS 04511 3MLABREQUNOE.US27T23 WILDLIFE INTERNATIONAL, 10 "15. APPENDIIXI - AnalyticalMethod ProvidedbySponsor `methodSsr:anples willbeanalyzed basedupon procedure provide bytheSpousorinthefollowinganalytical L LRMeiecqlduliiuduormCoohcrioamoagtSouglrfaopnhiycMAacisdsPoStpaescstiruommeStarlyt((LPCROMSS))IMneFtrheoshdwfaotrert,hSealDtewtaetremrinaantdiAolngoalf analyAz tchoeptyeotfstahmepalbeoswvielmlebtehdoodcwuimlelntbeemdiainnttheairnaewddianttahaenrdaswudmamtaar,Tizheed aictthualfminealtrehpoortd. kulsoedgtyo \ PROTOCOLNO.: 454/091799/NAV96/SUB4S4 I 04512 3MLABREQUENSOT. U2723 . WILDLIFE INTEO RNATIONt AL Lo. PROJECTNO 454-112 (hPagee llofl1 AMENDMENT TO STUDY PROTOCOL STUDY TITLE: (PNFaOvSi:culaApel9l6icHulOoUsaR) TOXICITY TEST WITH THE FRESHWATER DIATOM PROTOCOL NO: 454/091799/NAVI6/SUB4S4 SPONSOR: 3M Corporation AMENDMENT NO: 1 PROJECT NO.: 454A-112 EFFECTIVE DATE: February 23,2000 3MLABREQUESTNO: 12723 AMENDMENT: Page2 ~; Add: EExxppeerriimmeennttaall STtearrmtiDnaattei:onFDeabtreu:arFye2b5r,ua2r0y0209, 2000 . TTeesstt SCounbcsetnatnrcaetiNoon.s: 4N6e7g5ative Control, 70.0, 92.5, 125, 167, 225, . 300 and 395 mg aL/L REASON: Theaboveinformationwasnotknownwhen theprotocol wassignedbytheStudyDirector AMENDMENT: ExperimentalDesign, Page 3 Change: Targetconcentwrilalntotieoxcneesd 100mg/L.orth solubility limi ofthetestsubstanceinwater. To: `Targetconcentrationswillnotexceed 1000mg/Lorthesolubilitylimitofth testsubstanceinater REASON: Nominaltestconcentrations exceed 100 mg/L. Ero STUDY DI R J LABORATORY MANAGEMENT : yh DATE Pa -- A=LE Setitrne, SPORSORS REPRESENTATIVE ] DA 004513 hthep00 - W_ILDLIFE Ir NTERNATIOe NAL Lo. PROJECTNO.: 454A-112 0 PPaegelLoaf | AMENDMENT TO STUDY PROTOCOL STUDYTITLE: (NPFaOvSi:culaApel9li6c-uHloOsUaR) TOXICITY TEST WITH THE FRESHWATER DIATOM PROTOCOL NO: 454/091799/NAV96/SUB4S4 SPONSOR: 3M Corporation EFFECTIVEDATE:February 28, 2000 AMENDMENTNO.: 2 PROJECT NO.: 454A-112 3MLABREQUENSOT.: U2723 AMENDMENT:Biological MeasurementsPage 6 Add: - Atthe eadofthetest,algistatic effects,whichresultintheinhibitionofcellgrowth,willbedifferentiated from algicidaleffects,whichresultinthedeath ofcells.Aliquots(0.5mL) oftest solution willbetaken fromcachreplicateofthosetreatmentgroups wheregrowthismaximallyinhibited.`Maximallyinhibited treatmentsarethoseinwhichit cannotbevisuallydeterminedif livealgalcellsarepreseat(e.g,absence. c`ouflctoulroermteodtihuemtetsotsoalcuotnicoenn)t.r`aTthieosneoafltiqhuottesswtilslubbsetpaonoceltehdabtythceoonrceetinctarlaltyiosnhaonudlddinlouttaefdfweictthgurnotwrteaht.eAd ``nmeLgwatiitvheccounlttruroelwmieldlbieupmr.`epGarroewdtbhyodfiltuhteisnegsaub0c.u5l-tumrLeasliwqiuloltbfermoomnointoerneedgaftoirveacmoantxriomlruemploifcat9edtayos1t0o0 determinewhetherinhibition of growth observed during the testisreversible.Sampleswillbecollected forcellcountsatrecovery phase initiation,termination andatapproximately3-dayintervalsbetween initiationandtermination. `Therecovery phasemay beterminated oncealgalgrowthissufficientto indicatethatthealgalcellscollectedfrom thetreatmentgroups havefully recoveredfromeffectsdueto thetest substance.This will be determinedthroughvisualexamination ofthe recoverytestsolutions. REASON: Toadd arecoveryphasetotheprotocol. ( 2 A= oO STUDY DIRECTOR JRATOR} EMENT T a SPO= Nl SOROl AEFREe > SENT, AITfVEat= 2s -- 2/29/00 DATE SL) fo DATE' 00455114 Gh 0 wr