Document rB2mkxa646JgNkmGDQ2po6enV

C 0 V A4t'C-E-.""\ THE DEVELOPMENTSERVICESCOMF%NY UNAUDITED DRAFR August 20, 1998 Sponsor: 3M St.Paul,Minnesota FINAL REPORT Study Title: 4-Week CapsuleToxicityStudy with PerfluorooctanSeulfonicAcid PotassiumSalt(PFOS; T-6295) inCynomolgus Monkeys Author: PeterJ.Thomford, PhD Study Completion Date: To be determined Performing Laboratory: Covance LaboratoriesInc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595 Laboratory ProjectIdentifleation: Covance 6329-222 Sponsor ProjectIdentification: 3M Study No. T-6295.6 Page 1 of 212 Covance 6329-222 3M T-6295.6 COM[PLIANCE STATEMENT 4-Week CapsuleToxicityStudywithPerfluorooctanSeulfonicAcid PotassiumSalt(PFOS; T-6295)inCynomolgus Monkeys Allaspectsof thisstudywere inaccordancewiththeEnvironmentalProtectioAngency Good LaboratoryPracticeStandards,40 CFR 792. PeterJ.Thomford, PhD Date Study Director Covance LaboratorieIsnc. Andrew M. Seacat,PhD Date Study Monitor 3M 2 Covance 6329-222 3M T-6295.6 QUALITY ASSURANCE STATEMENT Thisreportw,iththeexceptioonfAppendices6,7,8,and9,hasbeenreviewedby the QualityAssuranceUnitofCovance LaboratorieIsnc.,inaccordancewiththe Environmental ProtectionAgency (EPA) Good Laboratory PracticeStandards, 40 CFR 792. The data in Appendices 6, 7, 8, and 9 were generatedby and are the responsibilitoyf the Sponsor and the Sponsor'sdesignees.The followinginspections were conducted and findingsreportedto the study directorand study director management. Written statusreportsof inspectionsand findingsareissued to Covance management according to standardoperatingprocedures. Inspection Dates From To 04/21/98 04/21/98 05/20/98 05/20/98 05/20/98 05/20/98 05/21/98 05/21/98 06/01/98 06/01/98 07/08/98 08/14/98 07/13/98 08/14/98 08/10/98 08/18/98 Phase ProtocolReview ProtocolAmendment Review ProtocolAmendment Review ClinicalLaboratory Inspection Postlife Data Review ProtocolAmendment Review Report Review Date Reported to Study Directorand Study DirectorManagement 04/21/98 05/20/98 05/20/98 05/21/98 06/01/98 07/13/98 08/14/98 08/18/98 Representative QualityAssurance Unit Date 3 Covance 6329-222 3M T-6295.6 STUDY IDENTIFICATION 4-Week CapsuleToxicityStudywithPerfluorooctanSeulfonicAcid PotassiumSalt(PFOS; T-6295)inCynomolgus Monkeys Test Material Sponsor StudyMonitor AltemateStudy Monitor Study Location Study Director Study Timetable StudyInitiatiDoante In-Life(ExperimentalS)tartDate In-LifeTenninationDate ExperimentalTerminationDate PerfluorooctanSeulfonicAcid Potassium Salt(PFOS; T-6295) 3M Toxicology Ser-vices Building220-2E-02,3M Center St.Paul,Minnesota 55144-1000 Andrew M. Seacat,PhD 3M 612.575.3161 Marvin T. Case,DVM, PhD 3M 612.733.5180 Covance LaboratorieIsnc. 3301 Kinsman Boulevard Madison,Wisconsin 53704-2595 PeterJ.Thomford, PhD Covance LaboratoriesInc. P.O.Box 7545 Madison,Wisconsin 53707-7545 608.241.7207 April17,1998 April23,1998 May 22, 1998 To be determined 4 KEY PERSONNEL Covance 6329-222 3M T-6295.6 StudyDirector StudyToxicologist Study Coordinator SupervisorL,argeAnimal Toxicology SupervisorD,ose Formulation SupervisorL,aboratoryAnimal Medicine ClinicaPlathologist SupervisorC,linicaPlathology AnatomicalPathologist SupervisorA,natomicalPathology PeterJ.Thomford, PhD Dale Aldridge,BS PatriciKa. McKee Pesik,BS, LAT MeechelleBordeaux,LAT DixieBushee,BS, LATG Donna J.Clemons, DVM, MS Diplomate,ACLAM RobertL.Hall,DVM, PhD Diplomate,ACVP (ClinicaPlathology) RonaldMarkevitch,BS, MT (ASCP) Thomas E. Palmer,PhD KimberlyW. Durland,BS, HT 5 Covance 6329-222 3M T-6295.6 ABSTRACT CONTENTS Page ...............................................................9........... PURPOSE ...............................................................1.1........... REGULATORY COMPLIANCE .............................................I.I........... TEST MATERIAL AND VEHICLE ..........................................1.1........... TestMaterial...........................................................I.I........... Vehicle................................................................1.1........... Reserve(Archive)Samples...............................................1.2........... Dispositio.n............................................................1.2........... TEST SYSTEM ...........................................................1.2........... TestAnimal ............................................................1.2........... Identificat.i.o.n........................................................1.2........... Acclimation............................................................1.2........... Housing and Maintenance................................................1.3........... Justificati.o.n..........................................................1.3........... PROCEDURES ............................................................1.4........... Group Designationsand Dose Levels.......................................1.4........... Dose Preparation........................................................1.4........... Dose Analyses..........................................................1.6........... Method ofAdministratio.n...............................................1.6........... ClinicaOlbservations....................................................1.6........... Body Weights ..........................................................1.7........... RectalBody Temperatures................................................1.7........... Blood Hormone Determination............................................1.7........... Serum PFOS Level Determination..........................................1.7........... ClinicaPlathology.......................................................1.8........... AdditionaBllood Collectio.n.............................................1.8........... Necropsy..............................................................1.9........... Pal@toyl CoA OxidaseDeterminations.....................................1.9........... CellProliferatiEovnaluation..............................................1.9........... LiverPFOS Determinatio.n...............................................1.9........... TissuePreservatio.n.....................................................1.9........... lestopatholog.y.........................................................2.0........... StatisticAanlalyses......................................................2.0........... RECORD RETENTION ......................................................2.1........... RESULTS ................................................................2.2........... Dose Analyses..........................................................2.2........... ClinicaOlbservations....................................................2.2........... Body Weights..........................................................2.2........... 6 Covance 6329-222 3M T-6295.6 CONTENTS (Continued) Page RESULTS (Continued) Food Consumption ......................................................2.2........... RectalBody Temperatures................................................2.2........... Blood Hormone Analyses.................................................2.3........... Serum PFOS IzvelDetermination..........................................2.3.......... ClinicaPlathology......................................................2.3........... CellProliferatiEovnaluation..............................................2.3........... LiverPFOS Determinatio.n...............................................2.4........... AnatomicalPathology...................................................2.4........... CONCLUSIONS ..........................................................2.4........... SIGNATURES ............................................................2.5........... REFERENCES ............................................................2.6........... PATHOLOGY REPORT ...................................................2.7........... COMMENTS ON THE DATA ...............................................3.0........... CODES, ABBREVIATIONS, AND UNITS ....................................3.1........... GeneralCodes and Abbreviation.s.........................................3.2........... Codes forClinicaPlathology..............................................3.3........... Abbreviationasnd UnitsforClinicaHlematology .............................3.5........... Abbreviationasnd UnitsforClinicaClhemistry...............................3.7........... Codes forAnatomicalPathology...........................................3.9........... TABLE 1 Summary ofClinicaOlbservations-A.M./Weekly.........................4.0........... 2 Summary ofClinicaOlbservations- 30 Minutes Postdose...................4.1........... 3 Summary ofClinicaOlbservations- 60 Minutes Postdose...................4.2........... 4 Summary ofClinicaOlbservations- 90 Minutes Postdose...................4.3........... 5 Summary ofClinicalObservations- Unscheduled .........................4.4........... 6 Summary ofBody Weight Data (kg).....................................4.5........... 7 Summary ofRectalBody TemperatureData (-C)...........................47........... 8 Summary ofClinicaHlematology Data -Day -7...........................4.9........... 9 Summary ofClinicaHlematology Data -Day 29 ...........................5.3........... 10 Summary ofClinicaClhemistryData -Day -7.............................5.7........... 11 Summary ofClinicaClhemistryData -Day 2..............................6.3........... 12 Summary ofClinicaClhemistryData -Day 7..............................6.9........... 13 Summary ofClinicaClhemistryData -Day 14.............................7.5........... 14 Summary ofClinicaClhemistryData -Day 29.............................8.1........... 15 Summary of ClinicalChemistry Data -Day 30 .............................8.7........... 16 Incidenceof MacroscopicObservations..................................8.9........... 17 Incidenceof MicroscopicObservations..................................9.0........... 7 Covance 6329-222 3M T-6295.6 CONTENTS (Conflnued) Page APPENDIX 1 .................................................................9.2............. ProtocolDeviations..........................................................9.3............ Protocol ....................................................................9.5............ ProtocolAmendment No. I ..................................................1.1.3............ Protocol Amendment No. 2 ..................................................1.1.5............ ProtocolAmendment No. 3 ..................................................1.1.7............. MaterialSafetyData Sheet ...................................................12.0............. APPENDIX 2 ................................................................1.2.6............. IndividualAnimal Fate Data .................................................1.2.7............ IndividualClinicalObservations..............................................1.28............. IndividualRectalBody Temperature Data (-C)..................................1.3.5............ APPENDIX 3 ................................................................1.3.7............. IndividualBody Weight Data (kg)............................................1.3.8............. APPENDIX 4 ................................................................1.4.0............. IndividualClinicalHematology Data ..........................................1.41............. IndividualClinicalChemistry Data ...........................................1.5.3............. APPENDIX 5 .................................................................1.8.5............ IndividualAnimal Pathology Data ............................................1.8.6............ APPENDIX 6 ................................................................1.9.8............. Summary and IndividualHormone Analyses Data ..............................1.9.9............. Figure I - Mean EstradiolData - Males ........................................2.0.3............ Figure 2 - Mean EstradiolData - Females ......................................2.0.4............ Figure3 - Mean TriiodothyronineData - Males ................................2.0.5............. Figure4 - Mean TriiodothyronineData - Females ...............................2.0.6............ APPENDIX 7 ................................................................2.0.7............. Dose Analysis.............................................................2.0.8............. APPENDIX 8 ................................................................2.0.9............. Serum and Liver PFOS Level Determinations ..................................2.1.0............ APPENDIX 9 ................................................................2.1.1............. CellProliferatioEnvaluation.................................................2.1.2............ 8 ABSTRACT Covance 6329-222 3M T-6295.6 The purposeofthisstudywas toprovidedatafordeterminingan estimated maximum-tolerateddose and lower dose levelstobe used ina chronictoxicitsytudyand toassesstheeffectof thetestmaterialP,erfluorooctanSeulfonicAcid PotassiumSalt (PFOS; T-6295),on criticaelnzyme levelsh,ormones,and otherselectedbiochemical parameters. Male and femalecynomolgus monkeys were assignedtothreegroups (two animals/sexin Group 1,threeanimals/sexinGroup 2,and one animal/sexin Group 3).Animals in Groups 2 and 3 receivedgelatincapsulescontaining0.02and 2.0PFOS/kg ofbody weight/day(mg/kg/day)r,espectiveltyr,ituratweidthlactose(1:999and 1:9,w:w, respectivelyA)n.imalsin Group 1 receivedgelaticnapsulescontaininlgactoseonly.The totalmaterialdose levelforeach group was 20.0mg/kg/day. Food was providedonce or twicedaily.Water was providedad libitum.The animals were observedtwicedaily(a.m.and p.m.)formortalitaynd moribundity.At leastonce daily,animalswere examined forabnormalitieasnd signsof toxicitya,nd food consumptionwas assessedqualitativelIyn.additiona,nimalswere observed approximately30,60,and 90 minutespostdoseforsignsof poor healthor abnormal behavior.Body weightdatawere collectetdwiceweekly beginning2 weeks before initiatiofntreatmento,n Day -1,on thefirsdtay of treatmenta,nd twiceweekly thereafterR.ectalbody temperatureswere recordedtwiceweekly beginning2 weeks beforeinitiatiofntreatment.Blood samplesforhormone analyses[estradioels,trone, estriotlh,yroidstimulatinhgormone,triiodothyroniMn)e, and thyroxin(T4)]were collectebdeforeinitiationf treatmentand predoseon Day 29. Serum was harvesteda,nd thesampleswere senttoAni LyticsInc.f,oranalyses.Blood samplesforserum PFOS concentratioannalyseswere collectebdeforeinitiationf treatmentand predoseon Days 2,3 (approximatel2y4 hoursafterthefirsatnd seconddose,respectively7),,14, and 29. Serum was harvesteda,nd samplesWere senttotheSponsor foranalyses.Blood sampleswere collectefdorhematologyand clinicaclhemistrytestsbeforeinitiatiofn treatmentand on Day 29. Inadditionb,lood forclinicaclhemistrytestswas collected predoseon Days 2,7,and 14. Additionalblood was collecteadtthetimeof exsanguinationa,nd sampleswere shippedtotheSponsorforpossiblefutureanalysis. On Day 30,theanimalswere anesthetizedw,eighed,exsanguinated,and necropsied.At necropsy,macroscopicobservationswere recorded,and selectedtissueswere collected 9 Covance 6329-222 3M T-6295.6 and preserved. In addition, a sample ofliverwas collectefdrom each animal for palmitoylCoA oxidaseactivitaynalyses.Representativseamplesoflivert,estesa,nd pancreaswere collectefdrom each animaland senttoPathologyAssociatesInternational forproliferaticoenllnuclearantigenevaluationA. sampleofliverwas collectefdrom each animal and sentto theSponsor forPFOS concentratioannalyses.l@Ecroscopic examinationswere done on theadrenalse,ye,femoralbone marrow, lung,liverk,idney, pancreas,spleen,testesa,nd thymus from each animal. AllanimalssurvivedtothescheduledsacrificeT.here were no testmaterial-related effectosn clinicaolbservationsb,ody weights,foodconsumption,rectalbody temperaturesc,linicaplathology,ormacroscopicor microscopicfindings. There were no apparenttestmaterial-relateefdfectosn estrone,estriolt,hyroid stimulatinhgormone,or thyroxin.There were no apparenttestmaterial-relateefdfectosn estradioolr triiodothyroniante0.02mg/kg/Oay.Given thelow number of animalsinthis study,itisnotpossibletodetermineconclusivelwyhethertherewas a test material-relateefdfecton estradioolr triiodothyroninEes.tradiolevelsforthemale and femalegiven2.0mg/kg/daywere numericallylower thanthoseofthecontrolanimalson Day 29 and theirespectivperestudyvalues.Triiodothyroninleevelsforthemale and femalegiven2.0mglkg/daywere numericallylower thanthoseof thecontrolanimalson Day 29;however,theirprestudyvalueswere alsoconsiderablylower thanthecontrol values.Triiodothyroninleevelsforanimalsgiven0 or0.02mg/kg/daywere numerically higheron Day 29 compared withtheirprestudylevelswhiletriiodothyronilnevelsfor animalsgiven2.0mg/kg/daywere numericallylower compared withtheirprestudy levels. Incynomolgus monkeys treatedwith0,0.02,or2.0mg PFOS/kgtday orallyforatleast 4 weeks,therewere no apparenttestmaterial-relateefdfectosn clinicaolbservations, body weights,food consumption,rectalbody temperatureso,r clinicaolr anatomical pathologyfindings.The one male and one femaletreatedwith2.0mg PFOS/kg/day appearedtohave lower levelsofestradiooln Day 29. Data from liverand serum PFOS analysesand cellproliferatieovnaluationwsillbe providedby theSponsorand Pathology AssociatesInternationarle,spectively. 10 PU"OSE Covance 6329-222 3M T-6295.6 The purpose of thisstudy was to provide data for determiningan estimated maximum-tolerated dose and lower dose levelsto be used in a chronic toxicitystudy and to assessthe effectof the testmaterial,PerfluorooctaneSulfonicAcid Potassium Salt (PFOS; T-6295), on criticaelnzyme levels,hormones, and other selectedbiochemical parameters. REGULATORY COWLIANCE All aspectsof thisstudy were done in accordance with the Environmental Protection Agency Good I-aboratoryPracticeStandards,40 CFR 792. TEST MATERIAL AND VEEL[CLE Test Material The testmaterial,PerfluorooctaneSulfonicAcid Potassium Salt(PFOS; T-6295), Lot No. 217, isa white to off-whitepowder. Itwas receivedatCovance on September 4, 1997. The testmaterialwas storedatroom temperature. Informationon synthesismethods, stabilityp,urity,composition,or othercharacteristics thatdefine the testmaterialison filewith the Sponsor. Vehicle The vehiclewas lactose(Spectrum,New Brunswick, New Jersey),Lot No. NNO192 (expiratiodnate February 13, 1999). Itwas receivedat Covance on March 30, 1998. The vehiclewas storedatroom temperature. Informationon synthesismethods, purity,composition,or othercharacteristictshatdefine thevehicleison filewith the manufacturer. Covance 6329-222 3M T-6295.6 Reserve (Archive) Samples A reserve sample (10 g each) of each lot of the testmaterial,vehicle, and each test material/lactosterituratiownas taken beforeinitiatioonf treatmentand storedatroom temperature.These samples willbe transferredto the Sponsor aftercompletion of the in-lifpehase. Disposition Remaining testmaterialwillbe retainedat Covance foruse in possiblefuturestudies. TEST SYSTEM Test Animal Young adulttoadultcynomolgus monkeys were obtainedfrom Covance Research ProductsInc.(Alice,Texas),on March 10,1998. The animals weighed 2.0 to 2.5kg at initiatioonf treatment. Identiflcation Each animal was assigneda permanent number upon arrivaland identifiewdith collartag beforeinitiatioonf treatment.All dataforan animal arerecorded under thisnumber. Acclimation Seven males and seven females were receivedon March 10, 1998, transferredfrom the Covance in-house stockcolony on March 16, 1998, and acclimatedin Animal Room 2015 for38 days beforeinitiatioonf treatment.In general,animals in this shipment appeared healthy.During acclimation,theanimals were examined for abnormalitiesindicativeof healthproblems. In addition,threetuberculosistests,a physicalexamination,and a fecalflotationforparasiteswere done on each animal. The physicalexamination done afterthe animals were receivedrevealedno major abnormalities.Resultsof the tuberculosistestswere negativefor allanimals;the results arerecorded in the data. The resultsof the fecalflotationtestsindicatedthe animals were negativeforparasiteova. One male and one female were eliminatedfrom study considerationbased on clinicalpathologyfindingsor abnormal fecalobservationsduring 12 Covance 6329-222 3M T-6295.6 acclimationT.here were sixmales and sixfemalesin therandomizationforassignment togroups(two animawsex inGroup 1,threeanimawsex in Group 2,and one animal/sex inGroup 3). Animals not selectefdorthestudywere transferretdo theCovance stock colony. Housing and Maintenance Animal Room 2015 was used forthisstudy.Environmentalcontrolsfortheanimalroom were settomaintain18 to29EC, a relativheumidityof30 to70%, and a 12-hourlight/12-houdrarkcycle.Variationsfrom theseconditionsaredocumented in the dataand areconsideredtohave had no effecton theoutcome ofthestudy. The animalswere housed individualliynstainlesssteelcages. Certifiepdrimatediet(#8726C,HarlanTeklad)was providedonce ortwicedaily.The lot numbers arerecordedinthedata.The dietisroutinelaynalyzedby themanufacturerfor nutritioncaolmponents and environmentalcontaminants.Resultsof specifiendutrient and contaminantanalysesareon filewithCovance-Madison. Fruitsor additional supplementswere provided,butdidnotrequireanalysis. Water was providedad libitum.Samples of thewaterareanalyzedforspecified microorganismsand envirorunentaclontaminants.The resultasreon filewith Covance-Madison. There were no known contaminantsinthedietorwateratlevelsthatwould have interferewdiththisstudy. Justification PFOS isa known hepaticperoxisomeproliferat(oPrP)intherat.When exposedtoPP, nonhuman primates(suchas thecynomolgus monkey) respondsimilarltyohumans (i.e.l,ow tono hepaticresponse)and thereforaerean appropriatheuman surrogate species. 13 PROCEDURES Covance 6329-222 3M T-6295.6 This studywas conductedinaccordancewiththeProtocoldatedApril17,1998,and ProtocolAmenchnent Nos. I through3. The protocolp,rotocolamendments, and protocoldeviationsareinAppendix 1. Group Designationsand Dose Levels Selectioonf animalsforthestudywas based on clinicaolbservationsc,linicaplathology, and otherdataas appropriateA.nimals were assignedtotreatmentgroupsusinga computerizedblockingproceduredesignedtoachievebody weightbalancewithrespect to treatmentgroup. Dose Level TotalMaterialDose Number of Animals Group 1 (control) (mglkg/day) oa Level(mg/kg/day) Males 20.oa 2 Females 2 2 (lowdose) 0.02 20.ob 3 3 3 (highdose) 2.0 20.Oc 1 1 a The controlgroup(Group 1)receivedan equivalentamount of lactosein gelaticnapsulesasthetotalmaterialadministeredtoGroup 3. b The low-dosegroupreceivedthetestmaterialtrituratweidthlactose (1:999w,:w). c The high-dosegroup receivedthetestmaterialtrituratewdith lactose (1:9w,:w). DosePreparation Gelaticnapsule(sTorpacI,nc.F,airfielNde,w Jersey)S,izeNo.2,LotNo. 122630 (expiratiodnateJune 26,2002),were usedfordose administrationT.he testmaterial trituratweidthlactoseand lactoseonly(controglroup)were dispensedintocapsulestwice weekly and storedatroom temperature. Vehicle.Lactosewas used as thevehicleinthedose preparationsD.ose levelswere basedon thevehicleas suppliedforGroup 1. 14 Covance 6329-222 3M T-6295.6 For Group I dose preparationst,hespecifieadmount oflactosewas weighed and transferreidntothegelatincapsule.The topand bottom halvesof each capsulewere joined,and thecapsulewas placedintotheappropriatceontainerlabeledwith study number, group number, animalnumber, and dose level. Test Material.For Group 2 and 3 dose preparationst,hetestmaterialwas dissolvedin acetoneand trituratweidthlactose(1:999and 1:9,w:w, respectivelyo)nce before initiatioofntreatmentA.cetone(Spectrum,Gardena,CaliforniaL)o,t No. LH0253 (expiratiodnateJune 2000)was usedto diluttehetestmaterialwithlactose.Trituration with lactosewas necessarytofacilitactaepsulepreparation. For Group 3 dose preparationst,hespecifieadmount oftestmaterialwas weighed,placed intoa labeledmixing containera,nd theappropriatveolume of acetonewas added tothe container.The preparatiownas stirremdanuallyuntilthetestmaterialwas dissolved. The specifieadmount of lactosewas weighed,placedintothemixing containera,nd thoroughlyn-@dxeudsinga spatula.This preparatiownas exposed toairuntiltheacetone was evaporatedand stirrepderiodicallyS.amples of thefinishedpreparatiofnordose analyseswere takendirectlfyrom thecontainer.The trituratteedstmaterialwas transferretdoa containerand storedatroom temperatureand protectedfrom lightand moisture. For Group 2 preparationst,herequiredamount of theGroup 3 preparatiownas measured and placedintoa labeledmixing container.The specifieadmount of lactosewas weighed,placedintothemixing containera,nd thoroughlymixed usinga spatulafor approximately5 minutes.Samples of thefinishedpreparatiofnordose analyseswere takendirectlfyrom thecontainer.The trituratteedstmaterialwas transferretdoa containerand storedatroom temperatureand protectedfrom lightand moisture. The specifieadmount of trituratetdestmaterialwas weighed and transferreidntothe gelaticnapsule.The top and bottom halvesof each capsulewere joined,and thecapsule was placedintotheappropriatceontainerlabeledwith studynumber, group number, animalnumber,and dose level. 15 Covance 6329-222 3M T-6295.6 Dose Analyses Samples(1g each)were collectefdrom thetop,middle,and bottomofthetest materiamactosepreparationfsorthelow- and high-dosegroupsand storedatroom temperature.The sampleswere shippedunder ambientconditionstotheSponsorfor analysis. Homogeneity samplescollectefdrom themiddle of thepreparationwsere used forthe prestudystabilitaynalysisO.ne setof samples(Ig each)were takenfrom thelow-and high-dosetestmaterialaactospereparationasttheend ofthein-lifpehase and shippedto theSponsor foranalysis. Resultsof thehomogeneity,stabilitayn,d dose confirmationanalysesprovidedby the SponsorareinAppendix 7. Method of Administration Gelatincapsuleswere used fortestmaterialpreparationadministratiotnocompare with datafrom previoustoxicologystudiesusingtheoralroute,which isthemost likelyroute ofexposure. The dose preparationwsere administeredorallyin gelaticnapsulesonce daily (7 days/week)for29 days(seeProtocolDeviationsforexceptions)T.he dosingtubes were flushedwith5 mL ofreverseosmosiswater.Individualdoseswere calculatebdased on themost recentlryecordedbody weights,withtheexceptionof body weightcollection dayswhen thepreviousbody weightwas used. Animals were dosed atapproximatelythe same time each day. ClinicalObservations The animalswere observedtwice daily(a.m.and p.m.)formortalityand moribundity. Each animalwas observeddaily,and food consumptionwas assessedqualitatively; abnormalfindingswere recorded.Animals were observedapproximately30,60,and 90 minutespostdoseforsignsof poorhealthor abnormalbehavior.Effectswere recordedas theywere observed.Animals were observedonce weekly;abnormal findings or an indicatioonfnormal was recorded. 16 Covance 6329-222 3M T-6295.6 Body Weights Individualbody weight datawere recorded twice weekly beginning 2 weeks before initiatioonf treatment(Monday and Thursday),on thefirstday of treatment,and twice weekly thereafter.An additionalbody weight was recorded on Day -1 fortheDay 1 dose calculations. Rectal Body Temperatures Rectal body temperatureswere taken atapproximately 11:00 twice weekly beginning 2 weeks beforeinitiatioonf treatment[Monday and Thursday (seeProtocolDeviations forexceptions)].Animals were not anesthetizedfortheprocedure. Blood Hormone Determination Approximately 5 mL of whole blood were collectedfrom a femoral vein of each animal beforeinitiatioonf treatment(Day -7)and predose on Day 29. Blood was collected between 07:00 and 09:00. Animals were fastedovernightbeforecollections.All samples were collectedwithout anticoagulant,maintained atroom temperature,and allowed to clot.Samples were centrifugedwithin I hour aftercollectiona,nd serum samples were harvested.Serum was dividedintotwo approximatelyequal aliquots(bloodcollectedon Day 29 only) and storedin a freezersetto maintain -60 to -80'C untilpacked on dry ice and shipped to Ani LyticsInc.,foranalyses.The samples were analyzed for estradiol, estrone,estriolt,hyroidstimulatinghormone, triiodothyronin(eT3),and thyroxin(T4). Resultsof theseanalyseswere provided by Ani LyticsInc.,and are in Appendix 6. Serum PFOS Level Determination Approximately 5 (Day -7 only)or 2 mL of whole blood were collectedfrom a femoral vein of each animal beforeinitiatioonf treatment(Day -7)and predose on Days 2, 3 (approximately24 hours afterthefirstand second dose,respectively)7,, 14,and 29. Animals were fastedovernightbeforecollections.All samples were collectedwithout anticoagulantm,aintained atroom temperature,and allowed to clot.Samples were centrifugedwithin I hour aftercollectiona,nd serum was harvestedand storedin a freezersetto maintain -60 to -800C untilpacked on dry iceand shipped to the Sponsor foranalyses.The samples were analyzedfor PFOS. Results of analysesprovided by the Sponsor are in Appendix 8. 17 Covance 6329-222 3M T-6295.6 Clinical Pathology Blood sampleswere collectefdrom eachanimalon Days -7 and 29 forhematologyand clinicaclhemistrytests.In additionb,loodforclinicaclhemistrytestswas collectefdrom each animalpredoseon Days 2,7,and 14. Animals were fastedovernight;waterwas providedad libitum.Blood was collectefdrom thefemoralvein.The followingwere evaluated: Hematology red blood cell(erythrocytec)ount differentiballood cellcount hemoglobin segmented neutrophiclount hematocrit lymphocytecount mean corpuscularvolume monocyte count mean corpuscularhemoglobin eosinophilcount mean corpuscularhemoglobin concentration basophilcount platelectount blood cellmorphology whitebloodcell(leukocytec)ount reticulocytceount ClinicalChendstry glucose ureanitrogen creatinine totaplrotein albumin globulin totalbilirubin cholesterol triglycerides aspartatearninotransferase alanineaminowmsferase alkalinephosphatase gamma glutamyltransferase sorbitodlehydrogenase creatinekinase calcium inorganicphosphorus sodium potassium chloride serum bileacids amylase lipase pancreatic-specifaimcylase AdditionalBlood Collection Whole blood (approximately20 mL) was collectefdrom thevena.cavaof each animalat thetimeof exsanguinatio(nSeeProtocolDeviationsforexceptions)T.he anticoagulant was potassiumEDTA. Samples were transferreidntocontainer(sapproximately5 niL each)and storedina freezersettomaintain-60to -80'C untilpacked on dryiceand shippedto theSponsorpossiblefutureanalysis. 18 Covance 6329-222 3M T-6295.6 Necropsy On Day 30,animalsthatwere fastedovernightwere anesthetizewdith ketamine and xylazinew,eighed,bledforrequiredtestse,xsanguinateda,nd necropsied.Animals were necropsiedinrandom order. The necropsyincludeda macroscopicexaminationoftheexternalsurfaceof thebody;all orificest;hecranialcavityt;hebrainand spinalcord;thenasalcavityand paranasal sinusesc;ervicaltissuesand organs;and thethoracica,bdominal,and pelviccavitieasnd viscera. Palmitoyl CoA Oxidase Determinations A sample ofthe rightlaterallobeof liverwas collectedfrom each animal atscheduled sacrificeT.he sample was flash-frozeinnliquidnitrogenand storedin a freezersetto maintain-60 to-80'C untilanalyzedforpalmitoylCoA oxidaseactivity. CellProliferatioEnvaluation Representativseamplesofthelivert,estesa,nd pancreaswere collecteadnd preservedin zincfortnalinA.fterfixations,amplesforproliferaticoenllnuclearantigen(PCNA) evaluationwere embedded inparaffinand shippedtoPathologyAssociatesInternational forPCNA evaluationR.esultsof theevaluationprovidedby PathologyAssociates InternationarleinAppendix 9. Liver PFOS Determination A sample ofliverwas collectefdrom eachanimalatsacrificwee,ighed,flash-frozeinn liquidnitrogena,nd storedina freezersettomaintain-60 to-80'C untilpacked on dry iceand shippedwith plasma samplestotheSponsorforPFOS analysis.Resultsof these analysesprovidedby theSponsorareinAppendix 8. Tissue Preservation The followingtissue(swhen present)or representativseampleswere collectedand preservedin 10% neutral-bufferfeodrinalinu,nlessotherwisespecifiedf,orpossible futuremicroscopicexamination: 19 adrenal(2) aorta brain cecum cervix colon duodenum epididymis(2) esophagus eyes [preservedinDavidson=s fixativ(e2)] femur withbone marrow (articular surfaceof thedistaelnd) gallbladder heart ileum jejunum kidney(2) liver lung lymph node (mesenteric) mammary gland Covance 6329-222 3M T-6295.6 muscle(thigh) ovary(2) pancreas pituitary prostate rectum salivargyland[mandibular(2)] sciatincerve seminalvesicl(e2) skin spinalcord(cervicatlh,oracica,nd lumbar) spleen sternumwithbone marrow stomach testi(s2) thymus thyroid(2)withparathyroid trachea urinarybladder uterus vagina Histopathology The adrenalse,ye,femoralbone marrow, lung,liverk,idney,pancreas,spleen,testesa,nd thymus were embedded inparaffins,ectioneds,tainedwith hematoxylinand eosin,and examined microscopicallfyrom eachanimal(seeProtocolDeviationsforexceptions). Bone marrow smearsfrom thesternumof each animalatthescheduledsacrificweere prepared,stainedwith Wright'sstaina,nd retainedforpossiblexamination. StatisticaAlnalyses Only datacollecteodn or afterthefirsdtay oftreatmentwere analyzedstatistically. Statisticanlalyseswere notdone on datacollectedforGroup 3 due tothesmallnumber of animals. 20 Covance 6329-222 3M T-6295.6 one-way analysiosf variance[ANOVA (Winer,1971a)]was usedto analyzeinitiablody weights,rectalbody temperaturep,almitoylCoA oxidaseactivitieasn,d continuous clinicaplathologyvalues. I-evene'tsest(Uvene, 1960)was done totestforvariancehomogeneity.In thecaseof heterogeneitoyf varianceatp:50.05,transformationwsere used tostabiliztehevariance. ANOVA was done on thehomogeneous or transformeddata.IftheANOVA was significanDtu,nnett'st-tes(tDunnett,1964)was used forcontrolversustreatedgroup comparisons. One-way analysiosf covariance[ANCOVA (Winer,1971b)]was usedto analyzebody weights,withinitiablody weightsas thecovariate.AlthoughLevene'stestforvariance homogeneitywas done (seeabove),no transformationwsere used becausecovariance adjustmentremoved extraneousheterogeneityI.ftheANCOVA was significanlte,ast squaresmeans t-teswtas used forcontrolversustreatedgroup comparisons. For each sex,Group 2 was compared withGroup I (Control)G.roup comparisonswere evaluatedatthe5.0% two-tailepdrobabilitlyevel. RECORD RETENTION Allraw data,documentation,recordsp,rotocola,nd specimensgeneratedasa resultof thisstudywillbe archivedinthestoragefacilitioefsCovance-Madison fora periodof 1 year.One yearafterthesubmissionofthefinalreportt,heSponsor willdeterminethe finaldispositioonf thematerials.Allraw datastoredon magneticmedia and an original copy ofthefinalreportwillbe retainebdy Covance-Madison. Within 1 yearaftersubmissionofthefinalreporta,llof theaforementionedmaterials (asappropriatef)rom theSponsor'sdesignees(3M E.T.& S,Ani LyticsInc.,and PathologyAssociatesInternationawli)llbe senttotheSponsor (Andrew Seacat,PhD, 3M). 21 RESULTS Dose Analyses Resultsof analysesprovidedby theSponsorareinAppendix 7. Resultsof thedose analyseswillbe providedby theSponsor. Covance 6329-222 3M T-6295.6 ClinicalObservations Clinicalobservationasresummarized inTablesI through5;individuadlataarein Appendix 2. AllanimalssurvivedtothescheduledsacrificeT.here were no testmaterial-related clinicaolbservations. Body Weights Body weightdataaresummarized inTable 6;individuadlataarein Appendix 3. There were no apparenttestmaterial-relateefdfectosn body weights. Food Consumption Food consumption dataaresummarized inTable I (Summary of ClinicaOlbservations-A.M./Weekly);individuadlataareincludedintheindividual clinicaolbservationisnAppendix 2. There were no testmaterial-relateefdfectosn food consumption. RectalBody Temperatures Rectalbody temperaturedataaresummarized inTables7;individuadlataarein Appendix 2. There were no testmaterial-relateefdfectson rectalbody temperatures. 22 Covance 6329-222 3M T-6295.6 Blood Hormone Analyses Summary and individual hormone analyses data are in Appendix 6. Estradiol and triiodothyroninaenalysesdata areillustrateidnFigures 1 through 4 (Appendix 6). There were no apparent testmaterial-relateedffectson estrone,estriolt,hyroid stimulatinghormone, or thyroxin.There were no apparenttestmaterial-relateedffectson estradioolr triiodothyroninaet0.02 mg/kg/day. Given thelow number of animals in this study,itisnot possibleto determine conclusivelywhether therewas a test material-relateedffecton estradiolor triiodothyronineE.stradiollevelsforthe male and female given 2.0mg/kg/day were numericallylower than those of the controlanimals on Day 29 and theirrespectiveprestudyvalues. Triiodothyroninelevelsforthemale and female given 2.0mg/kg/day were numericallylower than those of thecontrolanimals on Day 29; however, theirprestudyvalues were alsoconsiderablylower than the control values.Triiodothyroninelevelsforanimals given 0 or 0.02 mg/kg/day were numerically higheron Day 29 compared with theirprestudylevelswhile triiodothyroninleevelsfor animals given 2.0 mg/kgtday were numericallylower compared with theirprestudy levels. Serum PFOS Level Determination Results of serum PFOS leveldeterminationprovided by the Sponsor are in Appendix 8. Results of the serum PFOS leveldeterminationwillbe provided by the Sponsor. ClinicalPathology Hematology and clinicalchemistry dataare summarized inTables 8 through 15; individualdata arein Appendix 4. The Pathology Report containsa discussionof the data. Administrationof PFOS had no effectson clinicalpathologytestresults. Cell ProliferationEvaluation Resultsof cellproliferatioenvaluationprovided by Pathology AssociatesInternationaalre in Appendix 9. 23 Covance 6329-222 3M T-6295.6 Resultsof thecellproliferatieovnaluationwillbe providedby PathologyAssociates International. Liver PFOS Determination ResultsofliverPFOS leveldeterminatiopnrovidedby theSponsorareinAppendix 8. ResultsoftheliverPFOS leveldeterminatiownillbe providedby theSponsor. Anatomical Pathology Incidencesofmacroscopicand microscopicobservationasresummarized inTables 16 and 17. IndividualdataareinAppendix 5. The PathologyReportcontainsa discussion of thedata. There were no testmaterial-relatmeadcroscopicormicroscopicchangesintheorgansand tissuesexamined. CONCLUSIONS Incynomolgus monkeys treatewdith0,0.02,or 2.0mg PFOS/kg/day orallyforatleast 4 weeks,therewere no apparenttestmaterial-relateefdfectosn clinicaolbservations, body weights,foodconsumption,rectablody temperatureso,r clinicaolranatomical pathologyfindings.The one male and one femaletreatedwith2.0mg PFOS/kg/day appearedtohave lower levelsofestradiooln Day 29. Data from liverand serum PFOS analysesand cellproliferatieovnaluationwsillbe providedby theSponsor and Pathology AssociatesIntemationalr,espectively. 24 SIGNATURES Covance 6329-222 3M T-6295.6 PatriciaK. McKee Pesik,BS, LAT Date Study Coordinator Covance LaboratorieIsnc. PeterJ.Thomford, PhD Date Study Director Covance LaboratorieIsnc. 25 Covance 6329-222 3M T-6295.6 REF'ERENCES Dunnett,C. W., "New TablesforMultipleComparisonswitha Control," Biometfics2,0:482-491(1964). Levene,H.,"RobustTestsforEqualityof Variances,C"ontributiontsoProbabilitayn Statistic(se,ds.I).Olkinetal.C,h. 25,pp.278-292,StanfordUniversitPyress:Stanford, Californi(a1960). Winer,B. J.,"Designand AnalysisofSingle-FactoErxperiments,"StatisticParlincil)les inExRerimentalDesign,Second Ed.,Ch. 3,pp. 149-260,McGraw-l-lillN:ew York, New York (1971a). Winer,B. J.,"AnalysisofCovariance,"StatisticParlinciRleisnExperimentalDesign, Second Ed.,Ch. 10,pp.752-812,McGraw-I-lillN:ew York,New York (1971b). 26 PATHOLOGY REPORT Covance 6329-222 3M T-6295.6 SUMMARY The purposeof thisstudywas toprovidedatafordeterminingan estimated maximum-tolerateddose and lowerdose levelstobe used ina chronictoxicitsytudyand toassesstheeffectofthetestmaterialP,erfluorooctanSeulfonicAcid PotassiumSalt (PFOS; T-6295),on criticaelnzyme levelsh,ormones,and otherselectedbiochemical parameters. Administrationof PFOS had no effectosn clinicaplathologytestresultasnd causedno testmaterial-relatmeadcroscopicor rm'croscopicchanges intheorgansand tissues examined. METHODS Three groupsof male and female cynomolgus monkeys were administeredthetest materialorallyviacapsuleata dose levelof 0 (controglroup;receivedthevehicle, lactose)0,.02,or 2.0mgtkg ofbody weight/day(mg/kg/day)for29 days.The control group had two animawsex, thelow-dosegroup had threeanimals/sexa,nd thehigh-dose group had one animal/sex. Blood was collectefdorhematologyand clinicaclhemistrytestsbeforeinitiatiofn treatment(Day -7)and on Day 29. In additionb,loodforclinicaclhemistrytestswas collecteodn Days 2,7,and 14. The animalswere sacrificeadnd necropsiedon Day 30; macroscopicobservationwsere recorded,and tissuewsere preservedin fixativaes specifiebdy theprotocol.Samples of liverwere collecteadnd frozenfordeterminatioonf hepaticpalmitoylCoA oxidaseactivitaynd fordeterminatioonf PFOS content(bythe Sponsor).Samples of livert,estesa,nd pancreaswere collecteadnd preservedinzinc formalinforevaluatioonfproliferaficoenllnuclearantigen(PCNA; by Pathology AssociatesInternationalM)i.croscopicexaminationswere done on adrenalse,ye,femoral bone marrow, lung,liverk,idney,pancreas,spleen,testesa,nd thymus from allanimals. Resultsof clinicaplathologytestfsorthecontroland low-dosegroupswere compared statistically. 27 RESULTS AND DISCUSSION Mortality All animals survived to the scheduled sacrifice. Covance 6329-222 3M T-6295.6 Clinical Pathology Individual values for hematology and clinicalchen-@dstrytestsare in Appendix valuesand the resultsof statisticcaolmparisons are in Tables 8 through 15. 4. Mean Day -7. Clinicalpathology testresultsindicatedno obvious group or individualhealth abnormalities. Days 2, 7,and 14. Administrationof thetestmaterialhad no effectson clinical chemistry testresultsatthesecollectionintervals. Statisticalsliygnificandtifferencesforclinicaclhemistryresultsbetween thecontroland low-dose groups were inconsistentover time and between the sexes. Several of the differenceswere similarto differencespresentatDay -7,and none of the differences exhibiteda strongdose relationship(i.e.t,hehigh-doseanimals did not exhibitnotable differencesforthe same parameters). Day 29. Administrationof the testmaterialhad no effectson hematology or clinical chemistry testresultsatDay 29. Statisticalsliygnificandtifferencesforred blood cellcount,neutrophilcount,monocyte count,and hepaticpaln-iitoCyolA oxidase were inconsistentbetween the sexes and exhibitedno dose relationshipS.tatisticalsliygnificandtifferencesfortriglycerideasnd alkalinephosphatase were similarto differencesobserved atDay -7. Anatomical Pathology Anatomical pathology findingsfor each animal are in Appendix 5. Incidencesummaries of the macroscopic and microscopic observationsare in Tables 16 and 17. 28 Covance 6329-222 3M T-6295.6 Week 5. There were no macroscopicand few microscopicfindingsintheorgansand tissueesxamined,and therewere no major differencebsetween controland treated animalsintheincidenceof any finding.Allmicroscopicobservationwsere considered incidentaalnd unrelatedtothetestmaterial. RobertL.Hall,DVM, PhD Date Diplomate,ACVP ClinicaPlathology Thomas E. Palmer,PhD Date Pathologist 29 COMMENTS ON THE DATA Covance 6329-222 3M T-6295.6 Variousmodels of calculatorcso,mputers,and computerprogramswere usedto analyze datainthisstudy.Because differenmtodels round offor truncatneumbers differently, valuesinsome tables(e.g.m,eans, standarddeviationso,r individuavlalues)may differ slightlfyrom thosein othertablesf,rom individuallcyalculatedata,orfrom statistical analysisdata.Neithertheintegritnyor theinterpretatioofnthedatawas affectedby these differences. Some tabular datawere compiled usingExcel'Version7.0software. The summary tablesforclinicaolbservationisndicattehenumber of animalsforwhich a conditionwas observedwithoutregardtothespecifincature,severityr,eversibility, number ofincidences/animaolr,thelengthof timetheconditionpersisted. Only observationostherthannormal areindicatedon thesummary clinicaolbservations tables. The day ofinitiatioofntreatmentis"Day l." 30 CODES, ABBREVIATIONS, AND UNITS GeneralCodes and Abbreviations Codes forClinicaPlathology Abbreviationsand UnitsforClinicaHlematology Abbreviationasnd UnitsforClinicaClhemistry Codes forAnatomicalPathology Covance 6329-222 3M T-6295.6 Note: The followinglistosf codes,abbreviationsa,nd unitsareusedby Covance. Some, butnotnecessarilayllo,f thisinformationmay be needed forthis report. 31 Covance 6329-222 3M T-6295.6 General Codes and Abbreviations WK N Mean; MEAN CAM SD; S.D.;STAND DEV; STANDARD DEV; sd NA p UNSCHED DISPATCH NIIN OBS Week. Number of measurements in a group. Arithmeticmean. Covariate-adjustemdean. Standarddeviation. Group 2 mean issignificantdliyfferent from themean ofthecontrolgroup (Group 1) atp # 0.05. No value;notapplicablen;otpresent. Present. Unscheduled. Observationstransferrefdrom thein-life module ofthedatacollectiosnystemto thenecropsymodule forreferenceduring necropsy.Observationsareduplicateosf thelastin-lifoebservations. Minute. Observation. Animal Death Codes: T Terminalsacrifice. 32 NS QS/QNS NR FS sc SH H SL L si I NF u DT/DOT DB Ti TE RE EE SE PC PD Pi PL PA co BB PLASMO NO AGG FR UTD NOCOAG Codes for Clinical Pathology Covance 6329-222 3M T-6295.6 GENERAL CODES No sample Quantitynot sufficient No repeat(sample volume not sufficienftorrepeatanalysis) Fibrinstrands Sample clotted Slightlyhemolyzed Hemolyzed Slightlylipenlic Lipemic Slightlyicteric Icteric Animal not fasted Unscheduled/moribund bleed Animal died on test Died during bleeding Technician judgment to repeattest Technical error(instrumentor technicianerrorthatresultsin unacceptable data,e.g.,unacceptable instrumentoutput,sample spillede,ntryof invaliddata) Recording error(recordedincorrectdata,e.g.,wrong number, spellingerror,incorrectdate) Entry error(incorreckteyboard entry) Sampling error Plateletsclumped Plateletsdecreased Plateletsincreased Plateletslarge Plateletsappear adequate Color interferewsith test Heinz bodies observed Plasmodium No aggregation Fractious Unable to determine No coagulation 33 Covance 6329-222 3M T-6295.6 Codes forClinicalPathology (Continued) RESULTS NOT INCLUDED IN STATISTICAL ANALYSES Hemolyzed clinicaclhemistryor coagulatiosnamples Samples from animalsatunscheduledintervals Prothrombintimes(PT)greaterthan50 seconds Activatedpartiatlhromboplastitnimes(PTT) greaterthan110 seconds Bleed times(BLETRVIE) greaterthan30 minutes CODES FOR BLOOD CELL MORPHOLOGY The followingscalewas usedtomeasure thedegreeofanisocytosi(sANISO), poikilocytos(iPsOIK),polychromasi(aPOLY), hypochromasia(HYPO), and toxic neutrophil(sTOXNEUT): Scale - 1 2 3 4 Degree Normal forthespecies Slight Moderate Marked Not applicable Presence Not present Rare Few Moderate Many 34 Covance 6329-222 3M T-6295.6 Abbreviationasnd UnitsforClinicaHlematology Test Red bloodcellcount Hemoglobin Hematocrit Mean corpuscularvolume Mean corpuscularhemoglobin Mean corpuscularhemoglobin concentration Platelectount Mean platelevtolume Reticulocytceount Absolutereticulocytceount Heinz body count Erythrocytesedimentationrate Prothrombintime Activatedpartiatlhromboplastitnime Thrombin time Activatedcoagulatiotnime Fibrinogen Fibrin/fibrinogdeengradationproducts Plateleatggregation Collagen Adenosine diphosphate Alpha 2-antiplasmin Bleedingtime Methemoglobin Plasma hemoglobin Myeloid/erythroriadtio Estimatedmyeloid/erythroirdatio White bloodcellcount Differentiballood cellcount Nucleatedredbloodcellcount Correctedwhiteblood cellcount Segmented neutrophiclount Band neutrophiclount Ly7mphocyte count Monocyte count Eosinophilcount Basophilcount Anisocytosis Polychromasia Abbreviation(Units) RBC (E6fUL orX106/(DL) HGB (G/DL) HCT (%) MCV (FL) MCH (PG) MCHC (%) PLT (E3/UL orX103 /(DL) MTV (FL) RETIC (%) RETIC (E3/UL orX,03 /(DL) HEINZ (%) ESR (MM/HR) PT (SEC) PTT (SEC) TT (SEC) ACT (SEC) FBR (MG/DL) FDP (TJG/ML) PAGG/COL PAGG/ADP ANTIPLAS BLE TIME (SEC) METHGB (%) PLA HGB (MG/DL) M/E RATIO EST M/E RATIO WBC (E3/UL orX,03 /(DL) NRBC (/100WBC) COR WBC (E3fUL orX,03 /(DL) N-SEG (E3/UL orX,03 /(DL)and % N-BAND (E3/UL orX103/(DL)and % LYWH (E3/ULorX,03 /(DL)and % MONO (E3/UL orX,03 /OL) and % EOSIN (E3/UL orX103 /(DL)and % BASO (E3fUL orX103 /(DL)and % ANISO (-,1,2,3) POLY (-1,,2,3) 35 Covance 6329-222 3M T-6295.6 Abbreviationsand UnitsforClinicaHlematology (Continued) Test Poikilocytosis Hypochromasia Howell-Jollbyodies Basophilicstippling Toxic neutrophils Atypicallymphocytes Aqueous whitebloodcellcount(righetye) Aqueous whitebloodcellcount(lefetye) Abbreviation(Units) POIK (-,1,2,3) HYPO (-,1,2,3) HJBODY (-1,,2,3,4) BASTIP (-,1,2,3) TOXNELLT 1,2,3,4) ATYPLYM 1,2,3,4) R EYE (WBC[UL) L EYE (WBCAJL) 36 Covance 6329-222 3M T-6295.6 Abbreviationasnd UnitsforClinicaClhemistry Test Glucose Urea nitrogen Urea Creatinine Totalprotein Albumin Globulin Albumin/globulirnatio Totalbilirubin Directbihrubin Indirecbtilirubin Cholesterol Triglyceride Urea nitrogen/creatinrianteio Totallipids Phospholipids High-densitylipoproteicnholesterol L.ow-densitlyipoproteicnholesterol Uricacid Aspartateaminotransferase Alanineaminotransferase Alkalinephosphatase Gamma glutamyltransferase Sorbitoldehydrogenase Lactatedehydrogenase Creatinekinase Amylase Lipase PalmitoylCoA oxidase Calcium Ionizedcalcium Inorganicphosphorus Sodium Potassium Chloride Magnesium Zinc Strontium Iron Abbreviation(Units) GLU (MG/DL) UN (MG/DL) UREA (MG/DL) CREAT (N4G/DL) T PRO (G/DL) ALB (G/DL) GLOB (G/DL) A/G RATIO T BILI(N4G/DL) D BILI(MG/DL) IBELI (MG/DL) CHOL (MG/DL) TRIG (MG/DL) UN/CREAT (RANO) T LI]PIDS(MG/DL) P LIPIDS (MG/DL) HDL (MG/DL) LDL (MG/DL) UA (MG/DL) AST/SGOT (IUIL) ALT/SGPT (IU/L) ALK PHOS (IUAL) GGT (IUAL) SDH (RUAL) LDH (ITJ/L) CK (RUAL) AMYLASE (IU/L) LI]PASE (][TJIL) PCOAO (IU/G) CA (MG/DL) ION CA (MG/DL) IPHOS (MG/DL) NA (MMOIJL) K (MMOLJL) CL (MMOLJL) MG (MEQAL orMG/DL) ZN (MG/L orPPM) SR (MGAL orPPM) FE (UG/DL) 37 Covance 6329-222 3M T-6295.6 Abbreviationasnd UnitsforClinicaClheniistry(Continued) Test Excessiron Totalironbindingcapacity Unbound ironbindingcapacity Percentironsaturation Plasma cholinesterase Red bloodcellcholinesterase Braincholinesterase Caudate putamen I-Iippocampus Frontalcortex Cerebellum Bicarbonate Serum hemoglobin Serum bileacids Fecalbileacids Average fecalweight Fecalbileacids(calculation) Osmolality Electrophoresis Albumin Alpha-1-globulin Alpha-2-globulin Betaglobulin Gamma globulin legh-densitlyipoprotein Low-densitylipoprotein Very-low-densitlyipoprotein Insulin Adrenocorticotropihcormone Cortisol Glucagon Triiodothyronine Thyroxine Pancreatic-specifaimcylase Creatinekinaseisoenzymes BB MB mm Abbreviation(Units) EX FE (UG/DL) TMC (UG/DL) UEBC (UG/DL) FE %SAT (%) CBEP (MU/ML) CBER (MU/ML) CBEB (MUftvfL) CAUD PUT (UMOILJG) HIPPOCAM (UMOIJG) F CORTEX (UMOIJG) CEREBELL (UM01JG) BICARB (MMOLIL) SER HGB (MG/DL) SBA (UMOLIL orMG/DL) FBA (UG/ML) FCC WGT (G) FBA (MG/Day) OSMO (MOSM/KG) E ALB (G/DL) E A-1 (G/DL) E A-2 (G/DL) E BETA (G/DL) E GAMMA (G/DL) E-HDL (%) E-LDL (%) E-VILDL (%) INSULJN (UU/ML) ACTH (PG/NIL) CORTISOL (UG/ML) GLUCAGON (PG/ML) T3 (NG/DL) T4 (UG/DL) P AMYL (U/L) CK-BB (U/L) CK-MB (U/L) CK-MM (UAL) 38 Covance 6329-222 3M T-6295.6 Codes for Anatomical Pathology NUCROSCOPIC CODES Distribution Focal Diffuse Multifocal of Findings Grades for Severityor Amount 1 Minimal - the leastamount of change thatcan be observed with the lightmicroscope 2 Slight- lessthan average amount of change, but readilydiscernible as abnormal 3 Moderate -the average amount of change thatisexpected for a lesion 4 Moderately severe(marked) - a marked amount of change with possiblelossof functionof the affectedcellsor organs 5 Severe -a greatamount of change with probable lossof functionof the affectedcellor organs and frequentlyinvolveslargeareasof the organ 39 Table 1 Summary of Clinical Observations A.M./Weekly 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ------------------------------------------------------------------------------------------------------------------ NUMBER OF ANIMALS AFFECTED DAYS 1-30 CATEGORY SEX: GROUP: DOSE: -----MALE ---- 1. 2 3 0 0.02 2 ----FEMALE--- 1 2 3 0 0.02 2 KEYWORD QUALIFIER NUMBER: .2 3 1 2 3 1 ------------------------------------------------------------------------------------------------------------------ *** TOP OF LIST APPEARANCE SWOLLEN LIP(S) 0 0 0 1 0 0 DISCHARGE VOMITUS CONTAINING APPEARS TO FOOD BE MENSTRUATING 0 0 1 0 0 0 0 0 0 0 1 0 DISCHARGE UNKNOWN FOUND IN PAN RED IN COLOR SOURCE 0 0 1 0 0 0 EXCRETION FEW FECES NON-FORMED FECES SKIN & PELAGE RED SKIN LIP(S) SCAB(S) MOUTH 0 0 0 0 0 1 0 0 0 2 0 0 0 0 0 1 0 0 0 0 0 1 0 0 QUALITATIVE FOOD LOW END OF LIST CONSUMPTION 0 1 0 1 0 1 40 Table 2 Sunnary of Clinical Observations 30 Minutes Postdose 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ------------------------------------------------------------------------------------------------------------------ NUMBER OF ANIMALS AFFECTED DAYS 1-29 CATEGORY SEX: GROUP: DOSE-. -----MALE ---- 1 2 3 0 0.02 2 ----FEMALE--- 1 2 3 0 0.02 2 KEYWORD QUALIFIER NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------------------------------------------------ *** TOP OF LIST APPEARANCE SWOLLEN LIP(S) 0 0 0 1 0 0 EXCRETION NON-FORMED FECES SKIN & PELAGE RED SKIN LIP(S) SCAB(S) MOUTH END OF LIST 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 1 0 0 41 Table 3 Summary of Clinical observations 60 Minutes Postdose 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ----------------------------------------------------------------------------------------------------------------- DAYS 1-29 NUMBER OF ANIMALS AFFECTED CATEGORY KEYWORD SEX: GROUP: DOSE: -----MALE ---- 1 2 3 0 0.02 2 ----FEMALE--- 1 2 3 0 0.02 2 QUALIFIER NUMBER: 2 3 1 2 3 1 ----------------------------------------------------------------------------------------------------------------- *** TOP OF LIST APPEARANCE SWOLLEN LIP(S) 0 0 0 1 0 0 EXCRETION MUCOID FECES 1 0 0 0 0 0 SKIN & PELAGE RED SKIN LIP(S) SCAB(S) MOUTH END OF LIST 0 0 0 1 0 0 0 0 0 1 0 0 42 Table 4 Summary of Clinical Observations 90 Minutes Postdose 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS AFFECTED DAYS 1-29 SEX: GROUP: -----MALE ---- ----FEMALE--- 1 2 3 1 2 3 CATEGORY DOSE: 0 0.02 2 0 0.02 2 KEYWORD QUALIFIER NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------------------------------------------------ *** TOP OF LIST APPEARANCE SWOLLEN LIP(S) 0 0 0 1 0 0 SKIN & PELAGE RED SKIN LIP(S) SCAB(S) MOUTH END OF LIST 0 0 0 1 0 0 0 0 0 1 0 0 43 Table 5 Sunmary of Clinical Observations Unscheduled 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID ------------------------------------------------------------------------------------------------------------------ NUMBER OF ANIMALS AFFECTED DAYS 1-30 SEX: -----MALE ---- ----FEMALE--- GROUP: 1 2 3 1 2 3 CATEGORY DOSE: 0 0.02 2 0 0.02 2 KEYWORD QUALIFIER NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------------------------------------------------ *** TOP OF LIST DISCHARGE VOMITUS CONTAINING FOOD END OF LIST 0 1 0 0 0 0 44 Table 6 Sunmary of Body Weight Data (kg) 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ------------------------------------------------------------------------------------------------------------------ SEX: --------------M-ALE --------------- --------------FEMALE -------------- GROUP: 1 2 3 1 2 3 DOSE: 0 0.02 2 0 0.02 2 DAY UNITS: MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY ------------------------------------------------------------------------------------------------------------------ -14 m 2 3 1 MEAN 2.3 2.3 2.2 S.D. 0.00 0.21 -10 N 2 3 1 MEAN 2.3 2.3 2.2 S.D. 0.07 0.21 2 3 1 2.1 2.1 2.2 0.07 0.17 2 3 1 2.1 2.1 2.1 0.07 0.10 -7 N 2 3 1 MEAN 2.3 2.3 2.2 S.D. 0.07 0.21 -3 N 2 3 1 MEAN 2.3 2.3 2.2 S.D. 0.07 0.21 2 3 1 2.1 2.1 2.2 0.00 0.15 2 3 1 2.1 2.1 2.1 0.00 0.15 -1 N 2 3 1 MEAN 2.3 2.4 2.2 S.D. 0.00 0.25 1 N 2 3 1 MEAN 2.3 2.3 2.2 S.D. 0.14 0.21 5 N 2 3 1 CAM 2.3 2.3 MEAN 2.3 2.3 2.2 S.D. 0.07 0.17 2 3 1 2.1 2.1 2.2 0.00 0.20 2 3 1 2.1 2.2 2.2 0.00 0.15 2 3 1 2.0 2.1 2.0 2.1 2.1 0.00 0.15 45 Table 6 Summary of Body Weight Data (kg) 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONYEYS ------------------------------------------------------------------------------------------------------------------- SEX: ---------------MALE --------------- --------------FEMALE -------------- GROUP: 1 2 3 1 2 3 DOSE; 0 0.02 2 0 0.02 2 DAY UNITS: MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY ------------------------------------------------------------------------------------------------------------------- 8 N 2 3 CAM 2.5 2.4 MEAN 2.5 2.4 2.3 S.D. 0.07 0.12 12 N 2 3 1 CAM 2.5 2.3* MEAN 2.5 2.3 2.2 S.D. 0.07 0.12 15 N 2 3 1 CAM 2.4 2.4 MEAN 2.4 2.4 2.3 S.D. 0.14 0.06 19 N 2 3 1 CAM 2.5 2.4 MEAN 2.5 2.4 2.3 S.D. 0.07 0.06 22 N 2 3 1 CAM 2.5 2.4 MEAN 2.5 2.4 2.1 S.D. 0.07 0.10 26 N 2 3 1 CAM 2.5 2.4 MEAN 2.5 2.4 2.1 S.D. 0.07 0.10 29 N 2 3 1 CAM 2.4 2.4 MEAN 2.4 2.4 2.0 S.D. 0.07 0.06 2 3 2.2 2.2 2.2 2.2 2.2 0.07 0.20 2 3 1 2.1 2.1 2.1 2.2 2.2 0.00 0.15 2 3 1 2.2 2.2 2.2 2.2 2.1 0.07 0.20 2 3 1 2.1 2.3 2.1 2.3 2.3 0.00 0.17 2 3 1 2.2 2.2 2.2 2.2 2.1 0.07 0.15 2 3 1 2.2 2.2 2.2 2.2 2.1 0.07 0.15 2 3 1 2.1 2.1 2.1 2.1 2.1 0.00 0.15 46 Table 7 Summary of Rectal Body Temperature Data (*C) 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ------------------------------------------------------------------------------------------------------------------ SEX: ---------------MALE --------------- --------------FEMALE -------------- GROUP: 1 2 3 1 2 3 DOSE; 0 0.02 2 0 0.02 2 DAY UNITS: MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY ------------------------------------------------------------------------------------------------------------------ -14 N MEAN S.D. -10 N MEAN S.D. -7 N MEAN S.D. -3 N MEAN S.D. 2 39.8 0.28 2 40.0 0.35 2 39.8 0.57 2 39.6 0.28 3 39.2 0.57 3 39.2 0.40 3 39.0 0.72 3 39.2 0.45 1 39.6 1 39.5 1 39.1 1 39.2 2 40.2 0.28 2 39.8 0.49 2 39.9 0.21 2 39.8 0.49 3 40.1 0.50 3 39.7 0.55 3 40.0 0.38 3 39.8 0.10 1 40.0 1 39.8 1 39.9 1 39.7 1 N MEAN S.D. 5 N MEAN S.D. 8 N MEAN S.D. 2 39.0 0.57 2 38.9 0.07 2 38.5 0.35 3 39.4 0.30 3 39.1 0.59 3 39.2 0.40 1 39.4 1 39.9 1 39.6 2 39.6 0.35 2 39.0 0.35 2 39.1 0.42 3 39.9 0.29 3 39.8 0.25 3 39.8 0.21 1 39.5 1 39.7 1 39.9 47 Table 7 Summary of Rectal Body Temperature Data (oC) 4-WEEK CAPSULE TOXICITY STUDY WITH PERFTUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ------------------------------------------------------------------------------------------------------------------ SEX: --------------M-ALE --------------- --------------FEMALE -------------- GROUP: DOSE: DAY UNITS: 1 0 MG/KG/DAY 2 0.02 MG/KG/DAY 3 2 MG/KG/DAY 1 0 MG/KG/DAY 2 0.02 MG/KG/DAY 3 2 MG/KG/DAY ------------------------------------------------------------------------------------------------------------------ 12 N MEAN S.D. 2 39.0 0.07 3 39.1 0.47 1 40.0 2 39.2 0.14 3 39.8 0.25 1 39.7 15 N MEAN S.D. 2 39.7 0.00 3 39.7 0.42 1 39.7 2 39.7 0.57 3 40.0 0.20 1 39.8 19 N MEAN S.D. 2 38.7 0.21 3 38.7 0.64 1 38.9 2 39.0 0.35 3 39.3 0.21 1 39.3 22 N MEAN S.D. 2 39.4 0.21 3 39.5 0.57 1 39.4 2 39.6 0.42 3 39.8 0.25 1 39.4 26 N MEAN S.D. 2 38.8 0.07 3 39.2 0.38 1 39.2 2 39.0 0.35 3 39.6 0.15 1 39.1 29 N MEAN S.D. 2 38.5 0.42 3 38.8 0.35 1 38.9 2 38.8 0.14 3 39.1 0.38 1 39.2 48 Table 8 Summary of Clinical Hematology Data males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ RBC Xiol/gL -------- HGB G/DL -------- HCT % -------- mcv FL -------- MCH PG -------- MCHC % -------- PLT X101/tLL -------- RETIC RETIC % Xiol/gL -------- ------- 0 MEAN 5.64 14.0 42.6 75.4 24.8 32.9 502 .9 5 S.D. .332 1.41 3.82 2.26 1.06 .42 138.6 oo N 2 2 2 2 2 2 2 2 0.02 MEAN 5.18 12.6 39.1 75.4 24.4 32.4 454 .9 4 S.D. .272 .31 .90 2.21 1.10 .91 88.1 .53 2 N 3 3 3 3 3 3 3 3 2.0 MEAN 5.91 12.8 41.0 69.4 21.7 31.2 531 N 1 1 1 1 1 1 1 .7 4 1 49 Table 8 Summary of Clinical Hematology Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ 0 MEAN S.D. N 0.02 MEAN S.D. N 2.0 MEAN N WBC Xlo,/AL -------- N-SEG X101/tLL -------- LYMPH xlo,/PL -------- MONO XIO'/tLL -------- EOSIN X10'/ILL -------- BASO XIO'/ttL -------- N-SEG% -------- LYMPH% -------- MONO% -------- EOSIN% ------- 8.4 3.4 4.6 .4 .1 .0 40 54 4 1 .99 1.06 .07 .07 .14 .00 7.8 7.1 .7 1 2 2 2 2 2 2 2 2 2 2 9.2 1.00 3 2.9 1.33 3 5.8 1.46 3 .4 .1 .0 31 63 .20 .10 .00 16.5 14.6 3 3 3 3 3 4 1 2.0 1 3 3 8.2 2.8 4.8 .6 .0 .0 34 58 8 0 1 1 1 1 1 1 1 1 1 1 50 Table 8 Summary of Clinical Hematology Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ RBC HGB HCT mcv MCH MCHC PLT RETIC RETIC X101/iLL G/DL % FL PG % Xiol/RL % X101/tLL -------- -------- -------- -------- -------- -------- -------- -------- ------- 0 MEAN 5.25 13.3 40.4 76.9 25.4 33.1 478 .8 45 S.D. .325 1.34 3.96 2.69 .92 .00 180.3 .21 14 N 2 2 2 2 2 2 2 2 2 0.02 MEAN 5.00 12.8 39.1 78.2 25.6 32.7 430 .7 35 S.D. .241 .21 .21 3.30 1.55 .56 121.3 .17 8 N 3 3 3 3 3 3 3 3 3 2.0 MEAN 5.53 13.4 40.2 72.7 24.2 33.3 505 N 1 1 1 1 1 1 1 .8 44 1 1 51 Table 8 Sumnary of Clinical Hematology Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS DOSE mg/kg/day ------ 0 MEAN S.D. N 0.02 MEAN S.D. N 2.0 MEAN N WBC Xiol/PL -------- 9.0 1.48 2 10.2 1.97 3 11.7 1 N-SEG XIOI/tLL -------- 3.6 1.91 2 3.5 3.29 3 6.2 1 LYMPH X103/tLL -------- MONO X103/jiL -------- EOSIN Xlol/,LL -------- 5.1 .2 .0 .14 .20 .07 2 2 2 6.2 4.05 3 .4 .1 .12 .10 3 3 4.8 .4 .2 1 1 1 BASO Xlol/pL -------- .0 .00 2 .0 .00 3 .0 1 N-SEG% LYMPH% MONO% EOSIN% -------- -------- -------- ------- 38 58 2 0 14.8 11.3 3.5 2 2 2 2 36 59 4 1 34.2 32.9 1.5 1 3 3 3 3 53 42 4 1 1 1 1 1 52 Table 9 Suimary of Clinical Hematology Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ RBC Xiol/gL -------- HGB G/DL -------- HCT % -------- mcv FL -------- MCH PG -------- MCHC % -------- PLT Xlo,/gL -------- RETIC % RETI X101/ttL -------- ------ 0 MEAN 6.02 14.0 44.0 72.9 23.3 31.9 440 .8 S.D. .035 .64 1.84 2.69 .99 .21 116.7 .14 N 2 2 2 2 2 2 2 2 0.02 MEAN 5.12 12.6 39.1 76.4 24.6 32.2 392 .5 S.D. .262 .78 2.18 1.69 .61 .26 92.1 .35 N 3 3 3 3 3 3 3 3 2.0 MEAN 5.69 13.2 41.5 73.1 23.1 31.7 503 .2 N 1 1 1 1 1 1 1 1 53 Table 9 Summary of Clinical Hematology Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ 0 MEAN S.D. N 0.02 MEAN S.D. N 2.0 MEAN N WBC X,03 /tLL N-SEG Xiol/iLL LYMPH X101/ttL MONO X,03/tLL EOSIN Xiol/iLL BASO Xlo,/ILL N-SEG% LYMPH% MONO% EOSIN% -------- -------- -------- -------- -------- -------- -------- -------- -------- ------- 9.2 1.6 6.8 .6 .2 .0 is 74 6 2 .21 .49 .78 .21 .14 .00 5.7 7.1 2.8 1 2 2 2 2 2 2 2 2 2 2 8.8 1.0 6.9 .6 .2 .0 13 78 6 2 2.44 .15 2.27 .38 .10 .00 6.1 5.5 2.3 1 3 3 3 3 3 3 3 3 3 3 5.8 .9 4.4 .4 .0 .0 16 77 7 0 1 1 1 1 1 1 1 1 1 1 54 Table 9 Summary of Clinical Hematology Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ RBC HGB HCT mcv MCH MCHC PLT RETIC RETI Xiol/PL G/DL t FL PG % Xlo,/AL % Xiol/iLL -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN S.D. N 0,02 MEAN S.D. N 2.0 MEAN N 5.14 .170 2 5.13 .116 3 4.81 1 13.2 .78 2 13.1 .87 3 12.3 1 40.5 2.33 2 41.1 1.74 3 36.7 1 78.9 2.12 2 80.1 3.93 3 76.4 1 25.6 .71 2 25.5 1.80 3 25.6 1 32.5 .00 2 31.9 .81 3 33.6 1 511 182.4 2 425 116.7 3 529 1 1.2 .21 2 .8 .26 3 1.0 1 55 Table 9 Summary of Clinical Hematology Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROC)CTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ WBC Xiol/iLL N-SEG Xiol/PL LYMPH Xiol/AL MONO Xlo,/ILL EOSIN Xlo,/gL BASO Xlo,/ILL N-SEG% LYMPH% MONO% EOSII -------- -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN 11.1 3.8 6.2 1.0 .0 .0 36 54 10 S.D. 2.69 .14 2.55 .21 .00 .00 10.6 10.6 .7 N 2 2 2 2 2 2 2 2 2 0.02 MEAN 10.0 2.2 7.1 .6 .1 .0 22 70 6 S.D. 2.55 .45 2.67 .06 .00 .00 7.6 9.2 2.1 N 3 3 3 3 3 3 3 3 3 2.0 MEAN 15.7 7.2 7.9 .5 .1 .0 46 50 3 N 1 56 Table 10 Summary of Clinical Chemistry Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA uxnol/L CHOL MG/DL -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 0.02 MEAN S.D. N 2.0 MEAN N 82 24 1.0 8.2 5.2 3.0 .2 19.1 1.4 .07 .00 .00 .00 .07 2 2 2 2 2 2 2 a 155 .7 62.2 2 2 61 29 1.0 7.7 4.8 3.0 .3 13.2 2.0 .06 .06 .29 .32 .06 3 3 3 3 3 3 3 9 161 1.5 35.4 3 3 54 28 1.0 8.2 5.0 3.2 1 1 1 1 1 1 .4 10 150 1 1 1 57 Table 10 Summary of Clinical Chemistry Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID DOSE mg/kg/day ------ AST/SGOT IU/L ALT/SGPT IU/L ALK PHOS IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AMY U/L -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN S.D. N 48 4.9 2 40 9.2 2 612 36.1 2 88 4.9 2 4 228 .7 102.5 2 2 424 99.7 2 64 2 37.5 2 0.02 MEAN S.D. N 2.0 MEAN N 50 58 681 101 7.6 13.0 81.1 36.7 3 3 3 3 54 50 1086 117 1 1 6 214 315 1.2 17.2 63.1 3 3 3 5 220 244 62 2 61.2 3 7 1 58 c Table 10 Summary of Clinical Chemistry Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 0.02 2.0 MEAN S.D. N MEAN S.D. N MEAN N 10.7 .14 2 10.6 .52 3 11.4 1 7.2 .57 2 7.7 .71 3 8.7 1 162 2.1 2 159 5.0 3 162 1 5.8 .07 2 5.6 .47 3 5.9 1 110 .0 2 112 4.6 3 ill 1 59 Table 10 Summary of Clinical Chemistry Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/Dl; TRIG MG/D -------- -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN S.D. N 0.02 MEAN S.D. N 2.0 MEAN N 76 8.5 2 64 9.0 3 71 1 24 .0 2 26 4.6 3 27 1 1.0 .14 2 .9 .06 3 1.0 8.0 .49 2 7.9 .30 3 8.2 5.1 .42 2 4.9 .26 3 4.9 2.8 .07 2 3.0 .10 3 3.3 .5 4 142 .28 5.7 15.6 2 2 2 .4 9 154 .06 2.1 34.6 3 3 3 .3 12 141 1 60 c Table 10 Sunmary of Clinical Chemistry Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ AST/SGOT IU/L ALT/SGPT IU/L ALK PHOS IU/L GGT IU/L SDH IU/L CK IU/L ANYLASE IU/L LIPASE IU/L P AMYL U/L -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 0.02 2.0 MEAN S.D. N MEAN S.D. N MEAN N 99 76.4 2 58 6.7 3 53 1 53 21.2 2 58 14.2 3 55 1 593 66.5 2 828 65.5 3 683 1 80 2.1 2 74 10.1 3 110 1 6 1907 4.9 2286.8 2 2 4 385 1.0 163.0 3 3 3 1094 1 1 334 31.1 2 324 44.1 3 315 1 10 10.6 2 64 81.8 3 89 1 232 21.9 2 215 19.4 3 224 1 61 Table 10 Summary of Clinical Chemistry Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 0.02 2.0 MEAN S.D. N MEAN S.D. N MEAN N 11.0 .49 2 11.0 .59 3 11.3 7.4 1.27 2 8.0 1.72 3 6.8 159 2.8 2 158 6.7 3 165 7.2 1.91 2 5.8 .64 3 6.0 113 2.8 2 114 4.0 3 115 62 Table 11 Summary of Clinical Chemistry Data Males Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/D -------- -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 0.02 MEAN S.D. N MEAN S.D. N 57 7.1 2 62 6.0 3 25 5.7 2 24 2.3 3 .9 7.4 5.0 .00 .07 .07 2 2 2 .8 7.0 4.5 .06 .12 .12 3 3 3 2.4 .00 2 2.6 .23 3 .4 16 142 .07 4.2 64.3 2 2 2 .3 10 163 .06 .6 18.3 3 3 3 2.0 MEAN 58 21 .9 7.3 4.7 2.6 .4 N 1 1 1 1 1 1 1 9 151 1 1 63 Table 11 Summary of Clinical Chemistry Data Males Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMYL U/L -------- 0 0.02 2.0 MEAN S.D. N MEAN S.D. N MEAN N 75 14.1 2 41 2.5 3 54 1 56 21.2 2 56 14.8 3 55 726 48.8 2 599 82.7 3 1028 84 6.4 2 88 31.8 3 105 2 899 412 .7 5.7 69.3 2 2 2 2 579 .0 391.1 3 3 289 51.3 3 2 219 302 31 5.7 2 40 19.6 3 11 256 40.3 2 180 30.7 3 139 64 c Table 11 Summary of Clinical Chemistry Data Males Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 0.02 MEAN S.D. N MEAN S.D. N 10.2 .14 2 9.5 .26 3 6.8 1.06 2 6.7 .31 3 152 1.4 2 147 2.5 3 5.2 .07 2 4.7 .25 3 106 .7 2 108 4.0 3 2.0 MEAN 10.0 7.0 152 5.0 104 N 1 1 1 1 1 65 Co Table 11 Summary of Clinical Chemistry Data Females Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ GLU MG/DL LTN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/DL -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 0.02 2.0 MEAN S.D. N MEAN S.D. N MEAN N 70 19 .8 7.4 4.9 2.5 .4 14.1 .0 .07 .42 .28 .14 .07 2 2 2 2 2 2 2 8 145 42 .7 2.8 11 2 2 2 57 24 .8 7.3 4.7 2.6 .5 16 133 69 3.5 3.5 .06 .15 .30 .23 .06 1.0 2B.2 33 3 3 3 3 3 3 3 3 3 3 68 27 1.0 7.5 4.7 2.8 1 1 1 1 1 1 .4 17 136 47 1 1 1 1 66 c Table 11 Summary of Clinical Chemistry Data Females Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS DOSE mg/kg/day ------ AST/SGOT IU/L ALT/SGPT IU/L ALK PHOS IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AMYL U/L -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 58 18.4 2 72 43.1 2 578 123.0 2 81 5.7 2 2 .7 2 523 15.6 2 502 138.6 2 39 5.7 2 324 96.9 2 0.02 2.0 MEAN S.D. N MEAN N 54 4.5 3 46 1 57 16.9 3 55 1 805 65.3 3 672 1 69 8.1 3 100 1 2 .6 3 2 1 426 133.3 3 308 1 351 46.2 3 291 1 31 9.2 3 84 1 208 24.7 3 184 1 67 c Table 11 Summary of Clinical Chemistry Data Females Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 MEAN S.D. N 0.02 MEAN S.D. N 2.0 MEAN N 10.2 .71 2 10.0 .25 3 10.0 1 6.7 .28 2 7.6 .85 3 6.5 1 153 4.2 2 151 6.2 3 151 1 5.4 .64 2 4.9 .21 3 4.7 1 108 .0 2 105 2.3 3 106 1 68 c Table 12 Summary of Clinical Chemistry Data Males Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/DL -------- -------- -------- -------- -------- -------- -------- -------- -------- ------- 0 0.02 MEAN S.D. N MEAN S.D. N 81 20 .8 7.8 4.8 3.0 4.2 .0 .07 .28 .21 .07 2 2 2 2 2 2 68 21 .8 7.5 4.5 3.1 3.1 1.5 .06 .25 .06 .25 3 3 3 3 3 3 .2 10 138 5 .07 4.9 65.8 2 2 2 .3 10 156 5 .00 1.2 19.3 3 3 3 2.0 MEAN 63 18 .8 7.5 4.6 2.9 .4 N 1 1 7 137 5 69 Table 12 Summary of Clinical Chemistry Data males Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONYEYS DOSE mg/kg/day ------ AST/SGOT IU/L ALT/SGPT IU/L ALK PHOS IU/L GGT IU/L SDH IU/L CK IU/L ANYLASE IU/L LIPASE IU/L P AMYL U/L -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 0.02 2.0 MEAN S.D. N MEAN S.D. N MEAN N 51 15.6 2 39 3.8 3 46 1 46 13.4 2 57 15.0 3 49 1 770 78.5 2 556 106.4 3 1012 1 80 .0 2 85 34.6 3 98 1 0 249 .0 79.2 2 2 0 399 .0 415.4 3 3 0 270 1 1 397 67.9 2 327 35.6 3 260 1 33 7.1 2 31 13.5 3 0 1 272 48.1 2 225 24.1 3 139 1 70 c Table 12 Summary of Clinical Chemistry Data Males Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 MEAN S.D. N 0.02 MEAN S.D. N 2.0 MEAN N 10.2 .35 2 9.8 .32 3 10.3 1 7.0 .49 2 7.0 .35 3 6.6 1 156 3.5 2 152 3.6 3 156 1 5.2 .21 2 4.8 .29 3 5.1 1 112 .0 2 112 2.5 3 112 1 71 Table 12 Summary of Clinical Chemistry Data Females Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONYEYS DOSE mg/kg/day ------ GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/D -------- -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN 86 20 .8 8.0 4.6 3.5 .2 S.D. 9.2 6.4 .00 .07 .49 .42 .07 N 2 2 2 2 2 2 2 7 130 3 1.4 2.1 2 2 0.02 2.0 MEAN S.D. N 14EAN N 73 4.6 3 73 1 19 1.5 3 18 1 .8 8.0 4.8 .10 .17 .31 3 3 3 .8 7.9 4.6 1 1 1 3.2 .15 3 3.3 1 .3 a 147 .06 .0 31.3 3 3 3 .3 12 117 1 1 1 72 Co Table 12 Summary of Clinical Chemistry Data Females Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ AST/SGOT IU/L ALT/SGPT IU/L ALK PHOS IU/L GGT IU/L SDH IU/L CK IU/L ANYLASE IU/L LIPASE IU/L P AMYL U/L -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 0.02 2.0 MEAN S.D. N MEAN S.D. N MEAN N 46 .7 2 49 8.1 3 45 1 52 13.4 2 57 6.9 3 57 1 558 94.0 2 775 108.2 3 674 1 69 8.5 2 68 9.6 3 90 1 0 142 434 .7 55.2 26.9 2 2 2 30 10.6 2 303 26.9 2 0 218 356 .6 27.8 18.9 3 3 3 25 5.1 3 231 34.1 3 0 166 349 101 238 1 1 1 1 1 73 c Table 12 Summary of Clinical Chemistry Data Females Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 0.02 MEAN S.D. N MEAN S.D. N 11.0 .78 2 10.7 .40 3 6.1 .57 2 7.3 .78 3 156 2.1 2 155 6.1 3 6.4 .92 2 5.5 .20 3 112 .7 2 113 1.5 3 2.0 MEAN 10.6 6.4 155 5.3 113 N 1 1 1 1 1 74 c Table 13 Summary of Clinical Chemistry Data males Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/DL -------- -------- -------- -------- -------- -------- -------- -------- -------- ------- 0 MEAN S.D. N so 19 .8 7.7 5.0 2.7 .4 13.4 1.4 .07 .42 .28 .14 .00 2 2 2 2 2 2 2 8 141 3 2.1 58.0 2 2 0.02 2.0 MEAN S.D. N MEAN N 63 19 .7 7.2 4.5 2.7 .4 3.8 1.0 .23 .45 .17 .32 .00 3 3 3 3 3 3 3 64 15 1 1 .7 7.4 4.8 2.6 .4 1 1 1 1 1 8 150 4 2.1 12.2 3 3 6 132 2 1 1 75 Table 13 Summary of Clinical Chemistry Data Males Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ AST/SGOT IU/L ALT/SGPT IU/L ALX PHOS IU/L GGT IU/L SDH IU/L CK IU/L ANYLASE IU/L LIPASE IU/L P AMYL U/L -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 0.02 MEAN S.D. N 2.0 MEAN N 47 7.1 2 36 5.7 3 39 1 40 9.2 2 49 8.0 3 45 1 761 33.9 2 519 131.9 3 908 1 80 7.8 2 77 37.0 3 89 1 4 162 2.1 43.8 2 2 3 ill .6 35.2 3 3 2 245 1 1 394 30.4 2 306 40.8 3 242 1 35 8.5 2 35 18.6 3 2 1 262 20.5 2 203 28.9 3 123 1 76 Table 13 Summary of Clinical Chemistry Data Males Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS DOSE mg/kg/day ----- CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 0.02 2.0 MEAN S.D. N MEAN S.D. N MEAN N 10.2 .21 2 9.7 .15 3 10.1 1 7.6 1.63 2 6.7 .64 3 6.4 1 151 1.4 2 148 1.0 3 153 1 4.8 .28 2 4.5 .30 3 4.8 1 106 .7 2 107 1.0 3 108 1 77 Table 13 Summary of Clinical Chemistry Data Females Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 80 19 .6 7.5 4.6 2.8 .4 S.D. 3.5 4.2 .07 .14 .21 .35 .07 N 2 2 2 2 2 2 2 7 119 .0 11.3 2 2 0.02 2.0 MEAN S.D. N MEAN N 58 20 .7 7.7 4.8 2.9 .5 9.0 2.5 .20 .25 .30 .06 .15 3 3 3 3 3 3 3 59 18 .8 7.8 4.6 3.2 .4 1 1 1 1 1 8 139, 1.5 24.1 3 3 8 107 78 Table 13 Summary of Clinical Chemistry Data Females Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMYL U/L ------- 0 MEAN S.D. N 46 8.5 2 46 7.8 2 499 58.0 2 64 .7 2 4 259 .7 144.2 2 2 428 40.3 2 30 28 16.3 3 2 0.02 2.0 MEAN S.D. N MEAN N 47 7.5 3 40 1 55 11.3 3 51 1 800 68.6 3 727 1 63 10.4 3 86 1 3 307 320 .6 97.5 27.2 3 3 3 39 20 24.6 1 3 3 462 440 309 28 1 1 1 1 79 Table 13 Summary of Clinical Chemistry Data Females Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 MEAN 10.4 S.D. .49 N 2 6.8 .28 2 154 3.5 2 6.0 .71 2 110 .7 2 0.02 2.0 MEAN S.D. N MEAN N 10.4 .46 3 10.4 1 6.7 .69 3 6.1 1 151 6.8 3 152 1 5.2 .25 3 5.4 1 108 3.6 3 108 1 80 Table 14 Summary of Clinical Chemistry Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ GLU MG/DL LTN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 81 24 .8 7.6 4.6 3.0 .2 8.5 .0 .07 .14 .00 .14 .07 2 2 2 2 2 2 2 7 140 1.4 65.8 2 2 0.02 MEAN 73 24 .8 7.5 4.3 3.2 .2 10 151 S.D. 7.0 4.0 .15 1.04 .44 .65 .06 3.1 21.5 N 3 3 3 3 3 3 3 3 3 2.0 MEAN 80 15 1.1 8.2 4.8 3.4 .3 N 1 1 8 91 81 Table 14 Suimary of Clinical Chemistry Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ AST/SGOT IU/L ALT/SGPT IU/L ALK PHOS IU/L GGT IU/L SDH IU/L CK IU/L A14YLASE IU/L LIPASE IU/L P AMYL U/L -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 0.02 MEAN S.D. N 2.0 MEAN N 52 12.7 2 42 7.5 3 31 1 46 14.1 2 62 26.6 3 38 1 755 60.8 2 564 127.2 3 815 1 96 9.2 2 94 42.9 3 88 1 4 410 424 2.8 93.3 87.0 2 2 2 3 314 1.2 255.2 3 3 334 57.7 3 1 202 285 1 1 1 37 285 .0 62 2 2 35 228 33.9 39 3 3 3 156 1 1 82 Table 14 Summary of Clinical Chemistry Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 0.02 2.0 MEAN S.D. N MEAN S.D. N MEAN N 10.5 .14 2 10.2 .29 3 11.0 I 7.5 .99 2 6.3 .40 3 6.4 154 2.1 2 152 3.0 3 156 5.6 .92 2 5.1 .79 3 6.0 ill 1.4 2 110 2.0 3 107 83 Table 14 Summary of Clinical Chemistry Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLDGUS MONKEYS ACID DOSE mg/kg/day ------ GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- T m --- 0 0.02 2.0 MEAN S.D. N MEAN S.D. N MEAN N 86 25 .8 7.6 4.4 3.3 .2 .7 1.4 .07 .35 .07 .42 .00 2 2 2 2 2 2 2 9 121 2.8 19.8 2 2 62 24 .9 7.9 4.6 3.3 .3 10.8 3.8 .12 .57 .38 .20 .10 3 3 3 3 3 3 3 9 143 1.7 24.8 3 3 78 24 1.0 8.2 4.6 3.6 1 1 1 .2 17 62 84 Table 14 Summary of Clinical Chemistry Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID DOSE mg/kg/day ------ AST/SGOT IU/L ALT/SGPT IU/L ALK PHOS IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AMYL U/L -------- -------- -------- -------- -------- -------- -------- -------- ------- 0 MEAN S.D. N 0.02 MEAN S.D. N 2.0 MEAN N 53 9.9 2 45 7.1 3 36 46 9.2 2 54 5.7 3 47 467 69.3 2 908 68.8 3 637 72 3.5 2 76 7.6 3 93 6 298 538 130 37 3.5 51.6 133.6 157.7 9 2 2 2 2 3 273 340 1.2 79.2 46.1 3 3 3 23 21 14.7 3 3 2 341 326 18 22 85 Table 14 Summary of Clinical Chemistry Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 MEAN S.D. N 10.4 .21 2 6.4 1.06 2 152 1.4 2 5.7 .42 2 ill 2.8 2 0.02 2.0 MEAN S.D. N MEAN N 10.9 .46 3 11.1 6.9 .89 3 6.5 155 4.4 3 158 5.5 .10 3 5.7 ill 2.1 3 110 1 86 TaLble 15 Suumary of Clinical Chemistry Data Males Day 30 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS DOSE mg/kg/day ------ PCOAO IU/G -------- 0 MEAN 0 S.D. .7 N 2 0.02 MEAN 4 S.D. .6 N 3 2.0 MEAN 1 S.D. .0 N 1 87 Table 15 Summary of Clinical Chemistry Data Females Day 30 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ PCOAO IU/G -------- 0 MEAN 2 S.D. 2.8 N 2 0.02 MEAN 3 S.D. 3.5 N 3 2.0 MEAN S.D. N 1 .0 1 88 TABLE 16 Incidence of Macroscopic Observations 4-WEEK CAPSULE TOXICITY STUDY WITH POTASSIUM SALT (PFOS;T-6295) PERFLUOROOCTANE IN CYNOMOLGUS SULFONIC MONKEYS ACID ------------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL N UM BER -0F -AN IMA L S A SEX: ----- MALE ---- ----FEMLE--GROUP: -1- -2- -3- -1- -2- -3- ORGAN AND KEYWORD(S) OR PHRASE NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------ - ** TOP OF LIST ** GENERAL COMMENT (GC) .................................NUMBER EXAMINED: 2 3 1 2 3 1 BONE MARROW SMEAR TAKEN EYES - DAVIDSONS STAINS-PERINEUM/PERIANAL NO MACROSCOPIC LESIONS END OF LIST 2 3 1 2 3 1 2 3 1 2 3 1 0 0 0 0 1 0 2 3 1 2 2 1 89 TABLE 17 Incidence of Microscopic observations 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ------------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL N U M B E R - 0 F -A N IM A L S A SEX: -----MALE ---- ----FEMALE--GROUP: -1- -2- -3- -I- -2- -3- ORGAN AND FINDING DESCRIPTION NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------- ** TOP OF LIST ** EYE (EY) ........................................N.UM.B.E.R . EXAMINED: NOT REMARKABLE: 2 3 1 2 3 1 2 3 1 2 3 1 BONE, FEMUR (FE) .................................N.U.MB.E.R EXAMINED: NOT REMARKABLE: 2 3 1 2 3 1 2 3 1 2 3 1 MARROW, FEMUR (FM) ................................NU.M.B.ER EXAMINED: NOT REMARKABLE: 0 1 0 1 2 1 0 1 0 1 2 1 KIDNEY (KD) ......................................NU.M.BE.R. EXAMINED: NOT REMARKABLE: --INFILTRATE, LYMPHOPLASMACYTIC LUNG (LU) .......................................N.U.MB.E.R. EXAMINED: NOT REMARKABLE: 2 3 1 2 3 1 2 2 1 1 1 1 0 1 0 1 2 0 2 3 1 2 3 1 2 3 1 2 3 1 LIVER (LI) .......................................NU.M.BE.R. EXAMINED: NOT REMARKABLE: --INFILTRATE, LYMPHOPLASMACYTIC --INFLAMMATION, LYMPHOHISTIOCYTIC --LIPIDOSIS, SUBCAPSULAR (TENSION LIPIDOSIS) 2 3 1 2 3 1 2 2 1 0 1 1 0 1 0 1 2 0 0 0 0 1 0 0 0 0 0 1 0 0 90 TABLE 17 incidence of microscopic Observations 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ------------------------------------------------------------------------------------------------------------------ TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL N U M B E R - 0 F - A N IM A L S A SEX: ----- MALE ---- ----FEMALE--GROUP: -1- -2- -3- -1- -2- -3- ORGAN AND FINDING DESCRIPTION NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------- SPLEEN (SP) ......................................NU.M.BE.R. EXAMINED: NOT REMARKABLE: 2 3 1 2 3 1 2 3 1 2 3 1 PANCREAS (PA) ....................................N.UM.B.ER. EXAMINED: NOT REMARKABLE: 2 3 1 2 3 1 2 3 1 2 3 1 ADRENAL, CORTEX --HEMORRHAGE --THROMBUS ADRENAL, MEDULLA (AC) ..............................N.UM.B.ER EXAMINED: NOT REMARKABLE: (MA) .............................N.UM.B.ER EXAMINED: NOT REMARKABLE: 2 3 1 2 3 1 2 3 1 2 2 1 0 0 0 0 1 0 0 0 0 0 1 0 2 3 1 2 3 1 2 3 1 2 3 1 THYMUS (TH) ......................................NU.M.BE.R. EXAMINED: NOT REMARKABLE: 2 3 1 2 3 1 2 3 1 2 3 1 TESTIS (TE) ......................................NU.M.BE.R. EXAMINED: NOT REMARKABLE: --IMMATURE END OF LIST 2 3 1 0 0 0 0 0 0 0 0 0 2 3 1 0 0 0 91 APPENDIX 1 ProtocolDeviations Protocol ProtocolAmendment No. 1 ProtocolAmendment No. 2 , ProtocolAmendment No. 3 MaterialSafetyData Sheet Covance 6329-222 3M T-6295.6 I 92 Covance 6329-222 3M T-6295.6 Protocol Deviations Protocol. Group Designations and Dosage Levels. Dose levelswere 0, 0.02, and 2.0mg/kgtday. The controlgroup (Group 1) was to receivean equivalentamount of lactosein gelatincapsulesas the totalmaterialadministeredto Group 3. The total materialwas 20.0 mgtkgtday foreach group; however, the low- and high-dose groups were to receivetestmaterialtrituratewdith lactose(1:999,w:w, and 1:9,w:w, respectively). Actual Procedure. Because thecapsulebroke duringdose administrationt,hefollowing animals may not have receivedthefullamount of dose preparation:Animal No. 105350 (Group 1 male) on Day 1;Animal No. 105367 (Group 1 female)on Days 2, 7, and 14; Animal No. 105344 (Group 2 male) on Day 7; and Animal No. 105369 (Group 3 female) on Day 2. Protocol. Observation of Animals. Rectal Body Temperatures. "Beginning 2 weeks before initiatioonf treatment,rectalbody temperatureswillbe taken atapproximately 11:00 on two days/week (Monday and Thursday)." Actual Procedure. Rectalbody temperatureswere recordedbetween 12:50 and 13:30 on Day -14 and between 08:17 and 08:40 on Day -10. Protocol. Serum PFOS Level Determination. Frequency. "Before initiatioonf treatment (Day -7 or -6),and priorto treatmenton Days 2 (approximately24 hours afterthefirst dose),7, 14,and 29." Actual Procedure. On Day 2,incorrectblood collectiontubes were used forthe collectionof blood forclinicaclhemistrytest;thereforeb,lood collectedforserum PFOS leveldeterminationswas used forclinicalchemistrytests.Remaining serum from clinical chemistry testswas used as the Day 2 sample for serum PFOS leveldeterminations.In addition,whole blood (approximately2 mL) was collectedfrom a femoral vein of each animal beforetreatmenton Day 3 (approximately24 hours afterthe second dose). 93 ProtocolDeviations(Continued) Covance 6329-222 3M T-6295.6 Protocol.AdditionalBlood Collection."At scheduledand unschedulednecropsies, blood (asmuch as possibleu,p to20 mL) willbe collectedfrom animalsatthetime of exsanguination." Actual Procedure. Additionalblood was not collectedfrom Animal Nos. 105364 (Group 2 female),105365 (Group 2 female),and 105369 (Group 3 female). Protocol.Postmortem Procedures.TissuePreservation".The followingtissues(when present)from each animal willbe preservedin 10% neutral-bufferefdorinalinu,nless otherwisespecifiedf,orpossiblefuturemicroscopicexamination:" Actual Procedure. Femoral bone marrow from Animal Nos. 105349 and 105350 (Group I males),105344 and 105348 (Group 2 males),105345 (Group 3 male),105366 (Group I female),and 105364 (Group 2 female)were insufficientth;ereforet,hesetissues were not examined microscopicallyT.his tissueislistedwith theappropriatecomments inthe pathologydatasheetsforeach individualanimal. Summary tablesdo not includeit as having been examined. These deviationsarenot expectedtohave affectedtheresultsof thestudy. 94 Protocol I of 18 Covance 6329-222 3M T-6295.6 95 Covance 6329-222 3M T-6295.6 2 96 Covance 6329-222 3M T-6295.6 3 97 4 1 Covance 6329-222 3M T-6295.6 98 Covance 6329-222 3M T-6295.6 5 99 Covance 6329-222 3M T-6295.6 6 100 Covance 6329-222 3M T-6295.6 7 101 Covance 6329-222 3M T-6295.6 8 102 Covance 6329-222 3M T-6295.6 9 103 Covance 6329-222 3M T-6295.6 10 104 Covance 6329-222 3M T-6295.6 11 105 Covance 6329-222 3M T-6295.6 12 106 Covance 6329-222 3M T-6295.6 13 107 Covance 6329-222 3M T-6295.6 14 108 I 15 Covance 6329-222 3M T-6295.6 109 Covance 6329-222 3M T-6295.6 16 110 Covance 6329-222 3M T-6295.6 17 III Covance 6329-222 3M T-6295.6 18 112 ProtocolAmendment No. I Page I of 2 1 Covance 6329-222 3M T-6295.6 113 Page 2 of 2 Covance 6329-222 3M T-6295.6 114 ProtocolAmendment No. 2 1 of2 Covance 6329-222 3M T-6295.6 115 2 of2 Covance 6329-222 3M T-6295.6 116 Protocol Amendment No. 3 1 of 3 Covance 6329-222 3M T-6295.6 117 Covance 6329-222 3M T-6295.6 2 118 Covance 6329-222 3M T-6295.6 3 119 Material Safety Data Sheet Page I of 6 Covance 6329-222 3M T-6295.6 120 Page 2 of6 Covance 6329-222 3M T-6295.6 121 Page 3 of6 Covance 6329-222 3M T-6295.6 122 Page 4 of 6 Covance 6329-222 3M T-6295.6 123 Page 5 of 6 Covance 6329-222 3M T-6295.6 124 Page 6 of 6 Covance 6329-222 3M T-6295.6 125 APPENDIX 2 IndividualAnimal Fate Data IndividualClinicalObservations IndividualRectal Body Temperature Data ('C) Covance 6329-222 3M T-6295.6 126 APPENDIX individual Animal Fate Data Covan 4-WEEK CAPSULE TOXICITY STUDY WITH POTASSIUM SALT (PFOS;T-6295) PERFLUOROOCTANE IN CYNOMOLGUS SULFONIC MONKEYS ACID -------------------------------------------------------------------------------------------------------------------- ANI14AL NUMBER ------ 105349 105350 105344 105347 105348 105345 105366 105367 105364 105365 105370 105369 DOSE GROUP ----- 1 1 2 2 2 3 1 1 2 2 2 3 SEX ------ MALE MALE MALE MALE MALE MALE FE14ALE FEMALE FEMALE FEMALE FEMALE FEMALE DEATH CODE ----- T T T T T T T T T T T T TYPE OF DEATH ----------- SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED DESCRIPTION OF DEATH ------------------------- TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL TERMINAL TERMINAL TERMINAL SACRIFICE SACRIFICE SACRIFICE SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL TERMINAL TERMINAL SACRIFICE SACRIFICE SACRIFICE DATE OF DEATH -------- 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 DAY OF STUDY ------- 30 30 30 30 30 30 30 30 30 30 30 30 WEEK OF STUDY ------- 5 5 5 5 5 5 5 5 5 5 5 5 127 Cov Appendix 2 Individual Clinical Observations 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE CATEGORY GROUP: WK OF KEYWORD DEATH QUALIFIER MI DOSE: 0 MG/KG/DAY DAYS 1-30 'C' - COMMENTS LISTED AT END OF OBSERVATIONS F AM OBS 30MIN 90MIN DAY PM CHECK 60MIN DIS 105349 T 5 NORMAL NO REMARKABLE OBSERVATIONS 105350 T 5 EXCRETION MUCOID FECES NORMAL NO REMARKABLE OBSERVATIONS p 8 p 15 p - - - - 22 p - - - - 29 p - - - - 30 p - - - - 12 - - p - 1 p - - 8 p 15 p - - - - 22 p - - - - 29 p - - - - 30 p - - - - 128 Cov Appendix 2 Individual Clinical Observations 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNONOLGUS SULFONIC MONKEYS ACID ------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE CATEGORY GROUP: WK OF KEYWORD DEATH QUALIFIER N2 DOSE: 0.02 MG/KG/DAY DAYS 1-30 DAY 'C' COMMENTS LISTED AT END OF OBSERVATIONS F AM OBS 30MIN 90MIN PM CHECK 60MIN D 105344 T 5 NORMAL NO REMARKABLE OBSERVATIONS 105347 T 5 DISCHARGE VOMITUS CONTAINING FOOD NORMAL NO REMARKABLE OBSERVATIONS 105348 T 5 NORMAL NO REMARKABLE OBSERVATIONS QUALITATIVE LOW FOOD CONSUMPTION 1 p 8 p is p 22 p 29 p 30 p 4 1 p 8 p 15 p 22 p 29 p 30 p 1 p 8 p 15 p 22 p 29 p 30 p 15 p - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 129 Appendix 2 Individual Clinical Observations Covan 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS -------------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: M3 ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER DOSE: 2 MG/KG/DAY DAYS 1-30 'C' COMMENTS LISTED AT END OF OBSERVATIONS FO AM OBS 30MIN 90MIN DAY PM CHECK 60MIN DISP, 105345 T 5 DISCHARGE VOMITUS CONTAINING FOOD DISCHARGE UNKNOWN SOURCE 24 p FOUND IN PAN RED IN COLOR 15 p NORMAL NO REMARKABLE OBSERVATIONS I p 8 p 22 p 29 p 30 p p 130 Appendix 2 Individual Clinical observations Cova 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS -------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE CATEGORY WK OF KEYWORD DEATH QUALIFIER GROUP: Fl DOSE: 0 MG/KG/DAY DAYS 1-30 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS F AM OBS 30MIN 90MIN PM CHECK 60MIN DI.1 105366 T 5 EXCRETION NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 105367 T 5 APPEARANCE SWOLLEN LIP(S) EXCRETION NON-FORMED FECES 23 p 27 p 29 p 1 p 8 p 15 p 22 p 30 p - p - - - - 11 - p p p 13 - p p p 14 p - p 15 p - p p p 19 p - p p p 20 p - p p p 21 p - p p p 22 p - p p p 23 p - 24 - p p p 25 p p 26 p - p p p 30 p - 15 p - 27 p - 131 Appendix 2 Individual Clinical Observations Cova 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE CATEGORY GROUP: WK OF KEYWORD DEATH QUALIFIER Fl DOSE: 0 MG/KG/DAY DAYS 1-30 (CONTINUED FROM 105367 T PREVIOUS PAGE) 5 SKIN & PELAGE RED SKIN LIP(S) SCAB(S) MOUTH NORMAL NO REMARKABLE OBSERVATIONS QUALITATIVE LOW FOOD CONSUMPTION 'C' - COMMENTS LISTED AT END OF OBSERVATIONS F AM OBS 30MIN 90MIN DAY PM CHECK 60MIN DI 11 p p p 13 p p p 14 p - p 15 p - p p p 19 p - p p p 20 p - p p p 29 p - p p p I p - 8 p 4 p 132 Cov Appendix 2 Individual Clinical observations 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE CATEGORY WK OF KEYWORD DEATH QUALIFIER GROUP: F2 DOSE: 0.02 MG/KG/DAY DAYS 1-30 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS F AM OBS 30MIN 90MIN PM CHECK 60MIN D 105364 T 5 NORMAL NO REMARKABLE OBSERVATIONS 105365 T 5 DISCHARGE APPEARS TO BE MENSTRUATING NORMAL NO REMARKABLE OBSERVATIONS 105370 T 5 NORMAL NO REMARKABLE OBSERVATIONS 1 p 8 p 15 p - - - - 22 p - - - - 29 p - - - - 30 p - - - - 29 p - - - - 30 p - - - - 1 p - - - - 8 p is p 22 p p 8 p 15 p 22 p 29 p 30 p - - - - - - - - - - - - - - - - 133 COVE Appendix 2 Individual Clinical Observations 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLOUS SULFONIC MONKEYS ACID ------------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: F3 DOSE: 2 MG/KG/DAY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER DAYS 1-30 'C' - COMMENTS LISTED AT END OF OBSERVATIONS F AM OBS 30MIN 90MIN DAY PM CHECK 60MIN DI 105369 T 5 EXCRETION FEW FECES NOR14AL NO REMARKABLE OBSERVATIONS QUALITATIVE LOW FOOD CONSUMPTION 17 p p 8 p 15 p 22 p 29 p 30 p 26 p 134 Appendix 2 Individual Rectal Body Temperature Data (*C) Cova 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS -------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DAY DAY DAY DAY DAY DAY DAY DAY DAY -14 -10 -7 -3 1 5 8 12 15 -------------------------------------------------------------------------------------------------------------------GROUP: MALE I - 0 MG/KG/DAy 105349 105350 GROUP: 40.0 39.6 40.2 39.7 MALE 2 - 0.02 MG/KG/DAY 40.2 39.4 39.8 39.4 39.4 38.6 38.8 38.9 38.2 38.7 38.9 39.0 39.7 39.7 105344 105347 105348 GROUP: 39.0 39.8 38.7 39.0 39.7 39.0 MALE 3 - 2 MG/KG/DAY 38.4 39.8 38.8 39.2 39.7 38.8 39.7 39.4 39.1 39.3 39.5 38.4 39.4 39.4 38.7 39.3 39.5 38.6 39.8 40.0 39.2 105345 GROUP: 39.6 39.5 FEMALE 1 - 0 MG/KG/DAy 39.1 39.2 39.4 39.9 39.6 40.0 39.7 105366 105367 GROUP: 40.0 40.4 39.4 40.1 FEMALE 2 - 0.02 MG/KG/DAY 39.7 40.0 39.4 40.1 39.3 39.8 38.7 39.2 38.8 39.4 39.1 39.3 39.3 40.1 105364 105365 105370 GROUP: 40.6 39.6 40.1 40.1 39.1 40.0 FEMALE 3 - 2 MG/KG/DAY 40.3 39.6 40.2 39.9 39.7 39.8 40.2 39.7 39.7 40.0 39.5 39.8 40.0 39.6 39.9 40.0 39.5 39.8 40.2 40.0 39.8 105369 40.0 39.8 39.9 39.7 39.5 39.7 39.9 39.7 39.8 135 Appendix 2 Individual Rectal Body Temperature Data (*C) Covanc 3 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DAY DAY DAY 22 26 29 --------------------------------------------------------------------------------------------------------------------GROUP: MALE I - 0 MG/KG/DAY 105349 105350 39.2 39.5 38.7 38.8 38.2 38.8 GROUP: MALE 2 - 0.02 MG/KG/DAY 105344 105347 105348 40.0 39.7 38.9 39.4 39.5 38.8 38.8 39.1 38.4 GROUP: 105345 MALE 3 - 2 MG/KG/DAY 39.4 39.2 38.9 GROUP: FEMALE 1 - 0 MG/KG/DAY 105366 105367 39.3 39.9 38.7 39.2 38.7 38.9 GROUP: FEMALE 2 - 0.02 MG/KG/DAY 105364 105365 105370 40.1 39.6 39.8 39.8 39.5 39.6 39.3 38.7 39.4 GROUP: FEMALE 3 - 2 MG/KG/DAY 105369 39.4 39.1 39.2 136 APPENDIX 3 IndividuaBlody Weight Data(kg) Covance 6329-222 3M T-6295.6 - - 137 Appendix 3 Individual Body Weight Data (kg) Covan 4-WEEK CAPSULE TOXICITY STUDY WITH PERFUUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DAY DAY DAY DAY DAY DAY DAY DAY DAY -14 -10 -7 -3 -1 1 5 8 12 --------------------------------------------------------------------------------------------------------------------GROUP: 14ALE 1 - 0 MG/KG/DAY 105349 105350 2.3 2.2 2.2 2.2 2.3 2.2 2.2 2.4 2.4 2.3 2.3 2.3 2.3 2.3 2.4 2.3 2.5 2.5 GROUP: MALE 2 - 0.02 MG/KG/DAY 105344 105347 105348 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.5 2.4 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.3 2.2 2.5 2.5 2.5 2.5 2.6 2.5 2.4 2.5 2.4 GROUP: MALE 3 - 2 MG/KG/DAY 105345 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.3 2.2 GROUP: FEMALE 1 - 0 MG/KG/DAY 105366 105367 2.0 2.0 2.1 2.1 2.1 2.1 2.0 2.2 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.0 2.1 2.1 GROUP: FEMALE 2 - 0.02 MG/KG/DAY 105364 105365 105370 2.2 2.1 2.1 2.1 2.1 2.2 2.1 2.2 2.2 2.2 2.2 2.2 2.2 2.3 2.3 2.3 2.4 2.3 1.9 2.0 1.9 1.9 1.9 2.0 2.0 2.0 2.0 GROUP; FEMALE 3 - 2 MG/KG/DAY 105369 2.2 2.1 2.2 2.1 2.2 2.2 2.1 2.2 2.2 138 Appendix 3 Individual Body Weight Data (kg) Covanc 3 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ---------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DAY DAY DAY DAY 19 22 26 29 ---------------------------------------------------------------------------------------------------------------------GROUP: MALE 1 - 0 MG/KG/DAY 105349 105350 2.4 2.4 2.4 2.3 2.5 2.5 2.5 2.4 GROUP: MALE 2 - 0.02 MG/KG/DAY 105344 105347 105348 2.4 2.5 2.4 2.4 2.3 2.3 2.3 2.3 2.4 2.4 2.5 2.4 GROUP: MALE 3 - 2 MG/KG/DAY 105345 2.3 2.1 2.1 2.0 GROUP: FEMALE 1 - 0 MG/KG/DAY 105366 105367 2.1 2.1 2.1 2.1 2.1 2.2 2.2 2.1 GROUP: FEMALE 2 - 0.02 MG/KG/DAY 105364 105365 105370 2.2 2.2 2.2 2.1 2.5 2.4 2.4 2.3 2.2 2.1 2.1 2.0 GROUP: FEMALE 3 - 2 MG/KG/DAY 105369 2.3 2.1 2.1 2.1 139 APPENDIX 4 IndividualClinicalHematology Data IndividualClinicalChemistry Data Covance 6329-222 3M T-6295.6 140 -- Appendix 4 Individual Clinical Hematology Data Males Day -7 ANIMAL NLTMBER ------ 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID RBC X101/tLL -------- HGB G/DL -------- HCT % -------- mcv FL -------- MCH PG -------- MCHC % -------- PLT RETIC Xlo,/RL % -------- -------- RETIC Xiol/iLL -------- Group: 1 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 Dose Level: 0 5.41 5.88 13.0 15.0 5.64 .332 2 14.0 1.41 2 Dose Level: 0.02 4.97 5.49 5.09 12.3 12.7 12.9 5.18 .272 3 12.6 .31 3 Dose Level: 2.0 Dosage Unit- mg/kg/day 39.9 45.3 73.8 77.0 24.0 25.5 42.6 3.82 2 75.4 2.26 2 24.8 1.06 2 Dosage Unit: mg/kg/day 38.5 40.1 38.6 77.5 73.1 75.7 24.8 23.2 25.3 39.1 .90 3 75.4 2.21 3 24.4 1.10 3 Dosage Unit: mg/kg/day 32.6 33.2 32.9 .42 2 32.0 31.7 33.4 32.4 .91 3 404 .9 600 .9 502 .9 138.6 .00 2 2 473 358 531 454 88.1 3 1.3 .3 1.1 .9 .53 3 49 53 51 2.8 2 65 16 56 46 26.1 3 105345 5.91 12.8 41.0 69.4 21.7 31.2 531 .7 41 141 ANIMAL NLTMBER ------ Group; 1 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 Appendix 4 Individual Clinical Hematology Data males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID WBC X101/tLL -------- N-SEG Xlo,/RL -------- LYMPH Xiol/iLL -------- MONO Xlo,/AL -------- EOSIN X101/iLL -------- BASO Xlo,/PL -------- N-SEG% -------- LYMPH% MONO% -------- -------- EOSIN% -------- Dose Level: 0 9.1 4.1 7.7 2.6 8.4 .99 2 3.4 1.06 2 Dosage Unit: mg/kg/day 4.5 .4 .0 4.6 .3 .2 4.6 .4 .1 .07 .07 .14 2 2 2 .0 45 49 .0 34 59 .0 40 54 .00 7.8 7.1 2 2 2 5 0 4 2 4 1 .7 1. 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 10.3 3.2 6.3 .6 .2 .0 31 61 6 2 8.8 1.4 7.0 .4 .1 .0 15 79 4 1 8.4 4.0 4.2 .2 .0 .0 48 50 2 0 9.2 1.00 3 2.9 1.33 3 5.8 1.46 3 .4 .1 .0 31 63 4 1 .20 .10 .00 16.5 14.6 2.0 1. 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 8.2 2.8 4.8 .6 .0 .0 34 58 8 0 142 Appendix 4 Individual Clinical Hematology Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNONOLGUS SULFONIC MONKEYS ANIMAL NUMBER ------ ANISO POLY POIK HYPO TOXNEUT -------- -------- -------- -------- -------- ACID Group: 1 105349 105350 Dose Level: 0 - Dosage Unit: mg/kg/day Group: 2 105344 105347 105348 Group: 3 105345 Dose Level: 0.02 - Dose Level: 2.0 - Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day 143 ANIMAL NUMBER ------ Group: 1 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 Appendix 4 Individual Clinical Hematology Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID RBC X101/iLL -------- HGB G/DL -------- HCT % -------- mcv MCH FL PG -------- -------- MCHC % -------- PLT Xlo,/gL -------- RETIC % -------- RETIC X10'/tLL -------- Dose Level: 0 Dosage Unit: mg/kg/day 5.02 12.4 37.6 75.0 24.8 33.1 351 .7 35 5.48 14.3 43.2 78.8 26.1 33.1 606 1.0 55 5.25 13.3 40.4 76.9 25.4 33.1 478 .8 45 .325 1.34 3.96 2.69 .92 .00 180.3 .21 14. 2 2 2 2 2 2 2 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 4.77 13.0 38.9 81.5 27.2 33.3 355 .6 4.90 12.7 39.0 78.3 25.5 32.6 365 .9 5.25 12.6 39.3 74.9 24.1 32.2 570 .6 5.00 12.8 39.1 78.2 25.6 32.7 430 .7 .241 .21 .21 3.30 1.55 .56 121.3 .17 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 5.53 13.4 40.2 72.7 24.2 33.3 505 .8 29 45 32 35 8.5 3 44 144 ANIMAL NUMBER ------ Group: 1 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 14EAN S.D. N Group: 3 105369 Appendix 4 Individual Clinical Hematology Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID WBC Xiol/gL -------- N-SEG X101/tLL -------- LYMPH X101/tLL -------- MONO Xlol/;LL -------- EOSIN Xiol/iLL -------- BASO Xiol/gL -------- N-SEG% -------- LYMPH% -------- MONO% -------- EOSIN% -------- Dose Level: 0 Dosage Unit: mg/kg/day 7.9 2.2 5.2 .4 .1 .0 28 66 5 1 10.0 4.9 5.0 .0 .0 .0 49 50 0 0 9.0 3.6 5.1 .2 .0 .0 38 58 2 0 1.48 1.91 .14 .28 .07 .00 14.8 11.3 3.5 .7 2 2 2 2 2 2 2 2 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 8.6 1.6 12.4 1.6 9.6 7.3 10.2 1.97 3 3.5 3.29 3 Dose Level: 2.0 6.2 10.2 2.1 .5 .2 .5 .1 .3 .0 6.2 .4 .1 4.05 .12 .10 3 3 3 Dosage Unit: mg/kg/day .0 19 73 .0 13 82 .0 75 21 .0 36 59 .00 34.2 32.9 3 3 3 6 2 4 1 3 0 4 1 1.5 1.0 3 3 11.7 6.2 4.8 .4 .2 .0 53 42 4 1 145 Appendix 4 Individual Clinical Hematology Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ----- ANISO POLY POIK HYPO TOXNEUT -------- -------- -------- -------- -------- Group: 1 105366 105367 Group: 2 105364 105365 105370 Dose Level: 0 - Dose Level: 0.02 - Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Group: 3 105369 Dose Level: 2.0 - Dosage Unit: mg/kg/day - 146 ANIMAL NUMBER ------ Group: 1 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 Appendix 4 Individual Clinical Hematology Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID RBC X10'/IIL -------- HGB G/DL -------- HCT % -------- mcv FL -------- MCH PG -------- MCHC % -------- PLT Xiol/iLL -------- RETIC % -------- RETIC Xiol/iLL -------- Dose Level: 0 Dosage Unit: mg/kg/day 6.00 13.6 42.7 71.0 22.6 31.8 357 6.05 14.5 45.3 74.8 24.0 32.1 522 .9 54 .7 42 6.02 14.0 44.0 72.9 23.3 31.9 440 .8 48 .035 .64 1.84 2.69 .99 .21 116.7 .14 B. 2 2 2 2 2 2 2 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 4.90 12.2 38.1 77.8 24.9 32.0 448 5.05 12.1 37.6 74.5 23.9 32.1 286 5.41 13.5 41.6 76.8 25.0 32.5 443 .5 24 .2 10 .9 49 5.12 12.6 39.1 76.4 24.6 32.2 392 .5 28 .262 .78 2.18 1.69 .61 .26 92.1 .35 19. 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 5.69 13.2 41.5 73.1 23.1 31.7 503 .2 11 147 ANIMAL NUMBER ------ Group: 1 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 WBC Xiol/AL -------- Appendix 4 Individual Clinical Hematology Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID N-SEG X101/iLL -------- LYMPH X103/gL -------- MONO Xlo,/ILL -------- EOSIN Xlo,/AL -------- BASO Xlo,/ILL -------- N-SEG% -------- LYMPH% -------- MONO% -------- EOSIN% -------- Dose Level: 0 Dosage Unit: mg/kg/day 9.1 2.0 6.3 .7 .1 .0 22 69 8 1 9.4 1.3 7.4 .4 .3 .0 14 79 4 3 9.2 1.6 6.8 .6 .2 .0 18 74 6 2 .21 .49 .78 .21 .14 .00 5.7 7.1 2.8 1. 2 2 2 2 2 2 2 2 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 10.9 .9 8.8 1.0 .2 .0 9 ol 9 1 9.3 1.0 7.6 .4 .3 .0 10 82 5 3 6.1 1.2 4.4 .3 .1 .0 20 72 5 2 8.8 1.0 6.9 .6 .2 .0 13 78 6 2 2.44 .15 2.27 .38 .10 .00 6.1 5.5 2.3 1. 3 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 5.8 .9 4.4 .4 .0 .0 16 77 7 0 148 Appendix 4 Individual Clinical Hematology Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ANIMAL NUMBER ------ ANISO POLY POIK HYPO TOXNEUT -------- -------- -------- -------- -------- Group: I 105349 105350 Dose Level: 0 - Dosage Unit: mg/kg/day Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 105344 - 105347 - 105348 - Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 105345 - - 149 ANIMAL NUMBER ------ Group: I 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 Appendix 4 individual Clinical Hematology Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOWUS SULFONIC ACID MONKEYS RBC X101/ttL -------- HGB G/DL -------- HCT -------- mcv FL -------- MCH PG -------- MCHC -------- PLT RETIC Xiol/iLL -------- -------- RETIC X101/tiL -------- Dose Level: 0 Dosage Unit: mg/kg/day 5.02 12.6 38.9 77.4 25.1 32.5 382 1.0 50 5.26 13.7 42.2 80.4 26.1 32.5 640 1.3 68 5.14 13.2 40.5 78.9 25.6 32.5 511 1.2 59 .170 .78 2.33 2.12 .71 .00 182.4 .21 12. 2 2 2 2 2 2 2 2 2 Dose Level: 0.02 Dosage Unit; mg/kg/day 5.15 14.1 43.1 83.7 27.4 32.8 377 1.1 57 5.01 12.7 40.5 80.7 25.4 31.4 340 .7 35 5.24 12.5 39.8 75.9 23.8 31.4 558 .6 31 5.13 13.1 41.1 80.1 25.5 31.9 425 .8 41 .116 .87 1.74 3.93 1.80 .81 116.7 .26 14. 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 4.81 12.3 36.7 76.4 25.6 33.6 529 1.0 48 150 ANIMAL NUMBER ------ Group: 1 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 Appendix 4 Individual Clinical Hematology Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS WBC Xiol/AL -------- N-SEG X10'/;LL -------- LYMPH MONO Xiol/AL Xlo,/AL -------- -------- EOSIN Xlo,/AL -------- BASO Xlo,/AL -------- N-SEG% LYMPH% -------- -------- MONO% EOSIN% -------- -------- Dose Level: 0 Dosage Unit: mg/kg/day 9.2 3.9 4.4 .9 .0 .0 43 47 10 0 13.0 3.7 8.0 1.2 .0 .0 28 62 9 0 11.1 2.69 2 3.8 .14 2 Dose Level: 0.02 6.2 1.0 .0 2.55 .21 .00 2 2 2 Dosage Unit: mg/kg/day .0 36 54 10 0 .00 10.6 10.6 .7 2 2 2 2 2 8.7 1.7 6.2 .6 .1 .0 19 72 7 1 12.9 2.2 10.1 .5 .1 .0 17 78 4 1 8.3 2.6 5.0 .6 .1 .0 31 60 8 1 10.0 2.2 7.1 .6 .1 .0 22 70 6 1 2.55 .45 2.67 .06 .00 .00 7.6 9.2 2.1 3 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 15.7 7.2 7.9 .5 .1 .0 46 50 3 1 151 Appendix 4 Individual Clinical Hematology Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONYEYS ACID ANIMAL NUMBER ------ ANISO -------- POLY -------- POIK -------- HYPO -------- TOXNEUT k -------- Group: I 105366 105367 Dose Level; 0 - Dosage Unit: mg/kg/day Group: 2 105364 105365 105370 Dose Level: 0.02 - Dosage Unit: mg/kg/day Group: 3 105369 Dose Level: 2.0 - Dosage Unit: mg/kg/day - 152 ANIMAL NUMBER ------ Group: 1 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 Appendix 4 Individual Clinical Chemistry Data males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- TR MG/ ---- Dose Level: 0 Dosage Unit: mg/kg/day 95 25 1.0 8.2 5.2 3.0 .2 68 23 1.1 8.2 5.2 3.0 .3 82 24 1.0 8.2 5.2 3.0 .2 19.1 1.4 .07 .00 .00 .00 .07 2 2 2 2 2 2 2 8 ill 9 199 8 155 .7 62.2 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 46 29 .9 7.7 4.6 3.1 .3 11 137 71 27 1.0 7.7 5.1 2.6 .4 9 202 66 31 1.0 7.8 4.6 3.2 .3 8 145 61 29 1.0 7.7 4.8 3.0 .3 13.2 2.0 .06 .06 .29 .32 .06 3 3 3 3 3 3 3 9 161 1.5 35.4 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 54 28 1.0 8.2 5.0 3.2 .4 16 150 153 ANIMAL NUMBER ------ Group: 1 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 Appendix 4 Individual Clinical Chemistry Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L -------- -------- -------- GGT IU/L -------- SDH IU/L -------- cx AMYLASE IU/L IU/L -------- -------- LIPASE IU/L -------- P AMYL U/L -------- Dose Level: 0 52 33 45 46 48 4.9 2 40 9.2 2 Dose Level: 0.02 58 45 43 71 48 59 50 7.6 3 58 13.0 3 Dose Level: 2.0 54 50 Dosage Unit: mg/kg/day 638 91 4 587 84 3 612 88 4 36.1 4.9 .7 2 2 2 Dosage Unit: mg/kg/day 606 78 7 767 143 5 670 81 5 681 101 6 81.1 36.7 1.2 3 3 3 Dosage Unit: mg/kg/day 1086 117 5 156 301 228 102.5 2 200 208 233 214 17.2 3 220 353 494 424 99.7 2 376 318 250 315 63.1 3 244 37 90 64 37.5 2 132 38 17 62 61.2 3 7 242 340 291 69. 2 275 220 175 223 so. 3 144 154 Appendix 4 Individual Clinical Chemistry Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 105349 105350 MEAN S.D. N Dose Level: 0 10.6 7.6 10.8 6.8 10.7 .14 2 7.2 .57 2 Dosage Unit: mg/kg/day 161 5.7 110 164 5.8 110 162 2.1 2 5.8 .07 2 110 .0 2 Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 Dose Level: 0.02 10.3 7.8 11.2 6.9 10.3 8.3 10.6 .52 3 7.7 .71 3 Dose Level: 2.0 11.4 8.7 Dosage Unit: mg/kg/day 159 5.1 ill 164 5.8 117 154 6.0 108 159 5.0 3 5.6 .47 3 112 4.6 3 Dosage Unit: mg/kg/day 162 5.9 ill 155 Appendix 4 Individual Clinical Chemistry Data ANIMAL NUMBER ------ Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- TF MG/ ---- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day 105366 105367 SH MEAN S.D. N 70 24 .9 7.6 4.8 2.8 .3 82 24 1.1 8.3 5.4 2.9 .7 76 24 1.0 8.0 5.1 2.8 .5 8.5 .0 .14 .49 .42 .07 .28 2 2 2 2 2 2 2 8 131 0 153 4 142 5.7 15.6 2 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 105364 105365 105370 55 23 .9 8.2 5.2 3.0 .4 7 114 73 23 .8 7.9 4.8 3.1 .4 8 169 64 31 .9 7.6 4.7 2.9 .3 11 178 MEAN S.D. N 64 26 .9 7.9 4.9 3.0 .4 9.0 4.6 .06 .30 .26 .10 .06 3 3 3 3 3 3 3 9 154 2.1 34.6 3 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 105369 71 27 1.0 8.2 4.9 3.3 .3 12 141 156 Appendix 4 Individual Clinical Chemistry Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANI14AL NUMBER ------ AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- ANYLASE IU/L -------- LIPASE IU/L -------- P AMYL U/L -------- Group: 1 105366 105367 SH MEAN S.D. N Group: 2 Dose Level: 0 45 38 153 68 99 76.4 2 53 21.2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 546 81 3 640 78 10 593 80 6 66.5 2.1 4.9 2 2 2 Dosage Unit: mg/kg/day 290 3524 1907 2286.8 2 356 312 334 31.1 2 17 2 10 10.6 2 247 216 232 21.9 2 105364 105365 105370 MEAN S.D. N 60 64 51 58 6.7 3 45 73 55 58 14.2 3 755 849 881 828 65.5 3 62 80 79 74 10.1 3 5 253 4 567 3 334 4 385 1.0 163.0 3 3 281 369 321 324 44.1 3 21 158 12 64 81.8 3 193 228 225 215 19.4 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 105369 53 55 683 110 3 1094 315 89 224 157 Appendix 4 Individual Clinical Chemistry Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: I 105366 105367 SH MEAN S.D. N Dose Level: 0 10.6 6.5 11.3 8.3 11.0 .49 2 7.4 1.27 2 Dosage Unit: mg/kg/day 161 5.9 ill 157 8.6 115 159 2.8 2 7.2 1.91 2 113 2.8 2 Group: 2 105364 105365 105370 Dose Level: 0.02 10.6 6.4 10.8 7.7 11.7 9.8 Dosage Unit: mg/kg/day 154 5.1 110 155 6.1 114 166 6.3 118 MEAN S.D. N Group: 3 11.0 .59 3 8.0 1.72 3 Dose Level: 2.0 158 6.7 3 5.8 .64 3 114 4.0 3 Dosage Unit: mg/kg/day 105369 11.3 6.8 165 6.0 115 158 ANIMAL NUMBER ------ Group: 1 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 Appendix 4 Individual Clinical Chemistry Data Males Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- Dose Level: 0 52 29 62 21 57 25 7.1 5.7 2 2 Dose Level: 0.02 56 21 68 25 62 25 62 6.0 3 24 2.3 3 Dosage Unit: mg/kg/day .9 7.4 5.0 .9 7.3 4.9 .9 7.4 5.0 .00 .07 .07 2 2 2 Dosage Unit: mg/kg/day .8 7.1 4.4 .8 6.9 4.6 .9 7.1 4.4 .8 7.0 4.5 .06 .12 .12 3 3 3 2.4 2.4 2.4 .00 2 2.7 2.3 2.7 2.6 .23 3 .4 .3 .4 .07 2 .3 .3 .4 .3 .06 3 19 97 13 188 16 142 4.2 64.3 2 2 10 9 10 10 .6 3 149 184 157 163 18. 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 58 21 .9 7.3 4.7 2.6 .4 9 151 159 ANIMAL NUMBER ------ Group: 1 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 Appendix 4 Individual Clinical Chemistry Data Males Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMY U/L ------ Dose Level: 0 65 41 85 71 75 14.1 2 56 21.2 2 Dosage Unit: mg/kg/day 692 88 2 761 79 3 726 84 2 48.8 6.4 .7 2 2 2 903 895 899 5.7 2 363 461 412 69.3 2 35 2 27 2 31 2 5.7 2 Dose Level: 0.02 44 40 39 69 41 60 41 2.5 3 56 14.8 3 Dose Level: 2.0 54 55 Dosage Unit: mg/kg/day 531 68 2 691 125 2 575 72 2 599 88 2 82.7 31.8 .0 3 3 3 Dosage unit: mg/kg/day 1028 105 2 139 888 709 579 391.1 3 219 325 311 230 289 51.3 3 302 62 2 35 1 24 1 40 1 19.6 3 11 1 160 Appendix 4 Individual Clinical Chemistry Data males Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: I 105349 105350 MEAN S.D. N Dose Level: 0 10.1 7.6 10.3 6.1 10.2 .14 2 6.8 1.06 2 Dosage Unit: mg/kg/day 151 5.2 107 153 5.1 106 152 1.4 2 5.2 .07 2 106 .7 2 Group: 2 105344 iOS347 105348 MEAN S.D. N Group: 3 Dose Level: 0.02 9.7 7.0 9.6 6.6 9.2 6.4 9.5 .26 3 6.7 .31 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 147 5.0 110 150 4.5 110 145 4.7 103 147 2.5 3 4.7 .25 3 108 4.0 3 Dosage Unit: mg/kg/day 105345 10.0 7.0 152 5.0 104 161 ANIMAL NUMBER ------ Group: I 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 Appendix 4 Individual Clinical Chemistry Data Females Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 80 19 .8 7.1 4.7 2.4 .4 60 19 .9 7.7 5.1 2.6 .5 70 19 .8 7.4 4.9 2.5 .4 14.1 .0 .07 .42 .28 .14 .07 2 2 2 2 2 2 2 8 143 9 147 8 145 .7 2.8 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 60 24 .9 7.5 5.0 2.5 57 28 .8 7.3 4.4 2.9 53 21 .8 7.2 4.7 2.5 .5 15 102 .5 16 140 .4 17 157 57 24 .8 7.3 4.7 2.6 .5 16 133 3.5 3.5 .06 .15 .30 .23 .06 1.0 28.2 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 68 27 1.0 7.5 4.7 2.8 .4 17 136 162 ANIMAL NUMBER ------ Group: 1 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 Appendix 4 Individual Clinical Chemistry Data Females Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYMOMOLGUS SULFONIC MONKEYS ACID AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AM U/L ----- Dose Level: 0 45 42 71 103 58 18.4 2 72 43.1 2 Dosage Unit: mg/kg/day 491 77 1 665 as 2 578 81 2 123.0 5.7 .7 2 2 2 534 512 523 15.6 2 404 600 502 138.6 2 43 35 39 5.7 2 Dose Level: 0.02 54 43 59 76 50 53 54 4.5 3 57 16.9 3 Dosage unit: mg/kg/day 730 60 2 833 74 3 851 74 2 805 69 2 65.3 8.1 .6 3 3 3 281 543 455 426 133.3 3 298 376 380 351 46.2 3 21 33 39 31 9.2 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 46 55 672 100 2 308 291 84 163 Appendix 4 Individual Clinical Chemistry Data Females Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: I Dose Level: 0 Dosage Unit: mg/kg/day 105366 105367 9.7 6.5 150 5.0 108 10.7 6.9 156 5.9 108 MEAN S.D. N 10.2 .71 2 6.7 .28 2 153 4.2 2 5.4 .64 2 108 .0 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 105364 105365 105370 10.2 6.7 146 5.1 104 9.7 7.6 149 4.7 104 10.0 8.4 158 4.8 108 MEAN S.D. N 10.0 .25 3 7.6 .85 3 151 6.2 3 4.9 .21 3 105 2.3 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 105369 10.0 6.5 151 4.7 106 164 ANIMAL NUMBER ------ Group: 1 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 Appendix 4 Individual Clinical Chemistry Data Males Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 84 20 .8 7.6 4.7 2.9 .3 92 78 20 .9 8.0 5.0 3.0 .2 14 185 81 20 .8 7.8 4.8 3.0 .2 10 138 4.2 .0 .07 .28 .21 .07 .07 4.9 65.8 2 2 2 2 2 2 2 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 67 20 .8 7.5 4.4 3.1 .3 11 134 71 21 .7 7.3 4.5 2.8 .3 9 171 65 23 .8 7.8 4.5 3.3 .3 9 162 68 21 .8 7.5 4.5 3.1 .3 10 156 3.1 1.5 .06 .25 .06 .25 .00 1.2 19.3 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 63 18 .8 7.5 4.6 2.9 .4 7 137 165 ANIMAL NUMBER ------ Group: I 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 Appendix 4 Individual Clinical Chemistry Data Males Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMY U/L ------ Dose Level: 0 62 37 40 56 51 15.6 2 46 13.4 2 Dosage Unit: mg/kg/day 714 80 0 825 80 0 770 80 0 78.5 .0 .0 2 2 2 365 193 249 79.2 2 349 445 397 67.9 2 28 2 38 3 33 2 7.1 2 Dose Level: 0.02 42 40 41 66 35 66 39 3.8 3 57 15.0 3 Dosage Unit: mg/kg/day 477 65 0 677 125 0 514 65 0 556 85 0 106.4 34.6 .0 3 3 3 110 875 212 399 415.4 3 361 330 290 327 35.6 3 42 2 35 2 16 2 31 2 13.5 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 46 49 1012 98 0 270 260 0 1 166 Appendix 4 Individual Clinical Chemistry Data Males Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 105349 105350 MEAN S.D. m Dose Level: 0 10.0 7.3 10.5 6.6 10.2 .35 2 7.0 .49 2 Dosage Unit: mg/kg/day 153 5.0 112 158 5.3 112 156 3.5 2 5.2 .21 2 112 .0 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 105344 105347 105348 9.4 7.3 151 4.5 112 9.9 7.0 156 5.0 114 10.0 6.6 149 5.0 109 MEAN S.D. N Group: 3 105345 9.8 .32 3 7.0 .35 3 Dose Level: 2.0 10.3 6.6 152 3.6 3 4.8 .29 3 112 2.5 3 Dosage Unit: mg/kg/day 156 5.1 112 167 ANIMAL NUMBER ------ Group: 1 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 Appendix 4 Individual Clinical Chemistry Data Females Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID GLU UN MG/DL MG/DL -------- -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB T BILI SBA G/DL MG/DL umol/L -------- -------- -------- CHOL MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 80 25 93 16 .8 8.1 4.9 3.2 .3 .8 8.0 4.2 3.8 .2 86 20 .8 8.0 4.6 3.5 .2 9.2 6.4 .00 .07 .49 .42 .07 2 2 2 2 2 2 2 6 128 8 131 7 130 1.4 2.1 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 74 18 .8 8.1 5.1 3.0 .3 68 21 .7 7.8 4.5 3.3 .4 77 19 .9 8.1 4.9 3.2 .3 73 19 .8 8.0 4.8 3.2 .3 4.6 1.5 .10 .17 .31 .15 .06 3 3 3 3 3 3 3 8 8 8 8 .0 3 ill 162 168 147 31.3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 73 18 .8 7.9 4.6 3.3 .3 12 117 168 ANIMAL NUMBER ------ Group: I 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 Appendix 4 Individual Clinical Chemistry Data Females Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID AST/SGOT IU/L -------- ALT/SGPT ALK PHOS IU/L IU/L -------- -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AN U/L ----- Dose Level: 0 45 43 46 62 46 .7 2 52 13.4 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 492 75 1 625 63 0 558 69 0 94.0 8.5 .7 2 2 2 Dosage Unit: mg/kg/day 181 103 142 55.2 2 415 453 434 26.9 2 23 38 30 10.6 2 58 45 43 49 8.1 3 65 53 53 57 6.9 3 655 805 865 775 108.2 3 57 72 75 68 9.6 3 0 240 1 228 0 187 0 218 .6 27.8 3 3 364 334 369 356 18.9 3 21 31 24 25 5.1 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 45 57 674 90 0 166 349 101 169 Appendix 4 Individual Clinical Chemistry Data Females Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: I Dose Level: 0 Dosage Unit: mg/kg/day 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N 10.4 6.5 11.5 5.7 11.0 .78 2 6.1 .57 2 Dose Level: 0.02 10.7 6.8 10.3 6.9 11.1 8.2 10.7 .40 3 7.3 .78 3 155 5.7 112 158 7.0 113 156 2.1 2 6.4 .92 2 112 .7 2 Dosage Unit: mg/kg/day 151 5.7 ill 152 5.3 113 162 5.5 114 155 6.1 3 5.5 .20 3 113 1.5 3 Group: 3 105369 DoSe Level: 2.0 10.6 6.4 Dosage Unit: mg/kg/day 155 5.3 113 170 ANIMAL NUMBER ------ Group: 1 105349 105350 MEAN S.D. N Group: 2 105344 iOS347 105348 MEAN S.D. N Group: 3 105345 Appendix 4 Individual Clinical Chemistry Data Males Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID GLU MG/DL -------- LIN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 89 18 .9 8.0 5.2 2.8 .4 70 20 .8 7.4 4.8 2.6 .4 80 19 .8 7.7 5.0 2.7 .4 13.4 1.4 .07 .42 .28 .14 .00 2 2 2 2 2 2 2 6 100 9 182 8 141 2.1 58.0 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 60 is .6 7.2 4.4 2.8 61 20 .6 6.7 4.4 2.3 67 19 1.0 7.6 4.7 2.9 .4 10 136 .4 7 158 .4 6 156 63 19 .7 7.2 4.5 2.7 .4 3.8 1.0 .23 .45 .17 .32 .00 3 3 3 3 3 3 3 8 150 2.1 12.2 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 64 15 .7 7.4 4.8 2.6 .4 6 132 171 ANIMAL NUMBER ------ Group: 1 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 Appendix 4 Individual Clinical Chemistry Data Males Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P ANY U/L ------ Dose Level: 0 52 34 42 47 47 7.1 2 40 9.2 2 Dose Level: 0.02 42 41 34 48 31 57 36 5.7 3 49 8.0 3 Dose Level: 2.0 39 45 Dosage Unit: mg/kg/day 785 86 6 737 75 3 761 80 4 33.9 7.8 2.1 2 2 2 Dosage Unit: mg/kg/day 431 58 3 671 120 4 456 54 3 519 77 3 131.9 37.0 .6 3 3 3 Dosage Unit: mg/kg/day 908 89 2 131 193 162 43.8 2 97 85 151 ill 35.2 3 245 372 415 394 30.4 2 351 294 272 306 40.8 3 242 41 2 29 2 35 2 8.5 2 52 2 37 1 15 1 35 2 18.6 3 2 1 172 Appendix 4 Individual Clinical Chemistry Data males Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: I 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Dose Level: 0 10.1 8.8 10.4 6.5 10.2 .21 2 7.6 1.63 2 Dose Level: 0.02 9.7 7.4 9.5 6.4 9.8 6.2 9.7 .15 3 6.7 .64 3 Dosage Unit: mg/kg/day 152 4.6 105 150 5.0 106 151 1.4 2 4.8 .28 2 106 .7 2 Dosage Unit: mg/kg/day 148 4.5 108 .149 4.2 107 147 4.8 106 148 1.0 3 4.5 .30 3 107 1.0 3 Group: 3 105345 Dose Level: 2.0 10.1 6.4 Dosage Unit: mg/kg/day 153 4.8 108 173 ANIMAL NLTMBER ------ Group: I 105366 iOS367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group. 3 105369 Appendix 4 Individual Clinical Chemistry Data Females Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYMOMOLGUS SULFONIC ACID MONKEYS GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 77 22 .7 7.4 4.8 2.6 .4 82 16 .6 7.6 4.5 3.1 .3 80 19 .6 7.5 4.6 2.8 .4 3.5 4.2 .07 .14 .21 .35 .07 2 2 2 2 2 2 2 7 7 7 .0 2 127 ill 119 11.3 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 49 20 .9 7.9 5.1 2.8 .5 57 22 .5 7.4 4.5 2.9 .7 67 17 .7 7.7 4.8 2.9 .4 58 20 .7 7.7 4.8 2.9 .5 9.0 2.5 .20 .25 .30 .06 .15 3 3 3 3 3 3 3 6 ill 8 150 9 155 8 139 1.5 24. 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 59 18 .8 7.8 4.6 3.2 .4 8 107 174 ANIMAL NUMBER ------ Group: 1 T05366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 Appendix 4 Individual Clinical Chemistry Data Females Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMY U/L ------ Dose Level: 0 40 41 52 52 46 8.5 2 46 7.8 2 Dosage Unit: mg/kg/day 458 64 5 540 63 4 499 64 4 58.0 .7 .7 2 2 2 157 361 259 144.2 2 399 456 428 40.3 2 18 2 41 3 30 2 16.3 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 46 48 722 51 55 68 852 69 40 49 825 69 3 341 289 3 383 335 4 197 337 31 1 67 1 20 2 47 7.5 3 55 11.3 3 800 68.6 3 63 10.4 3 3 307 320 .6 97.5 27.2 3 3 3 39 2 24.6 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 40 51 727 86 3 462 440 309 2 175 Appendix 4 Individual Clinical Chemistry Data Females Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: I 105366 iOS367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 Dose Level: 0 10.1 6.6 10.8 7.0 10.4 .49 2 6.8 .28 2 Dose Level: 0.02 10.5 6.3 9.9 6.3 10.8 7.5 10.4 .46 3 6.7 .69 3 Dose Level: 2.0 10.4 6.1 Dosage Unit: mg/kg/day 152 5.5 110 157 6.5 109 154 3.5 2 6.0 .71 2 110 .7 2 Dosage Unit: mg/kg/day 146 5.2 105 149 5.0 107 159 5.5 112 151 6.8 3 5.2 .25 3 108 3.6 3 Dosage Unit: mg/kg/day 152 5.4 108 176 ANIMAL NUMBER ------ Group: 1 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 Appendix 4 Individual Clinical Chemistry Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO ALB G/DL G/DL -------- -------- GLOB T BILI G/DL MG/DL -------- -------- SBA umol/L -------- CHOL MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 75 24 .8 7.5 4.6 2.9 .3 87 24 .9 7.7 4.6 3.1 .2 81 24 .8 7.6 4.6 3.0 .2 8.5 .0 .07 .14 .00 .14 .07 2 2 2 2 2 2 2 6 93 8 186 7 140 1.4 65.8 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 66 22 .8 7.2 4.0 3.2 .2 9 129 73 22 .7 6.7 4.1 2.6 .2 7 151 80 29 1.0 8.7 4.8 3.9 .3 13 172 73 24 .8 7.5 4.3 3.2 .2 10 151 7.0 4.0 .15 1.04 .44 .65 .06 3.1 21.5 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 80 15 1.1 8.2 4.8 3.4 .3 8 91 177 ANIMAL NUMBER ------ Group: I 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 Appendix 4 Individual Clinical Chemistry Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- A14YLASE IU/L -------- LIPASE IU/L -------- P AM U/L ----- Dose Level: 0 61 36 43 56 52 12.7 2 46 14.1 2 Dose Level: 0.02 42 45 34 49 49 93 42 7.5 3 62 26.6 3 Dosage Unit: mg/kg/day 798 103 6 712 90 2 755 96 4 60.8 9.2 2.8 2 2 2 Dosage Unit: mg/kg/day 477 73 2 710 143 4 505 65 2 564 94 3 127.2 42.9 1.2 3 3 476 344 410 93.3 2 134 202 606 314 255.2 3 362 485 424 87.0 2 382 350 270 334 57.7 3 37 37 37 .0 2 73 24 8 35 33.9 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 31 38 815 88 1 202 285 3 178 Appendix 4 Individual Clinical Chemistry Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 Dose Level: 0 10.4 8.2 10.6 6.8 10.5 .14 2 7.5 .99 2 Dose Level: 0.02 10.0 6.7 10.0 5.9 10.5 6.3 Dosage Unit: mg/kg/day 152 6.3 112 155 5.0 110 154 2.1 2 5.6 .92 2 ill 1.4 2 Dosage Unit: mg/kg/day 149 4.8 108 152 4.5 112 155 6.0 110 MEAN S.D. N Group: 3 10.2 .29 3 6.3 .40 3 Dose Level: 2.0 152 3.0 3 5.1 .79 3 110 2.0 3 Dosage Unit: mg/kg/day 105345 11.0 6.4 156 6.0 107 179 ANIMAL NUMBER ------ Group: 1 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 Appendix 4 Individual Clinical Chemistry Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 87 26 .8 7.4 4.4 3.0 .2 11 107 86 24 .9 7.9 4.3 3.6 .2 7 135 86 25 .8 7.6 4.4 3.3 .2 .7 1.4 .07 .35 .07 .42 .00 2 2 2 2 2 2 2 9 121 2.8 19.8 2 2 Dose Level: 0.02 50 28 71 22 65 21 62 10.8 3 24 3.8 3 Dose Level: 2.0 78 24 Dosage Unit: mg/kg/day 1.0 8.5 5.0 .8 7.7 4.4 .8 7.4 4.3 .9 7.9 4.6 .12 .57 .38 3 3 3 Dosage Unit: mg/kg/day 1.0 8.2 4.6 3.5 3.3 3.1 3.3 .20 3 3.6 .4 8 114 .3 8 156 .2 11 158 .3 9 143 .10 1.7 24.8 3 3 3 .2 17 62 180 ANIMAL NUMBER ------ Group: I 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 Appendix 4 Individual Clinical Chemistry Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AV U/L ----- Dose Level: 0 46 39 60 52 53 9.9 2 46 9.2 2 Dose Level: 0.02 53 49 44 60 39 52 45 7.1 3 54 5.7 3 Dose Level: 2.0 36 47 Dosage Unit: mg/kg/day 418 70 9 516 75 4 467 72 6 69.3 3.5 3.5 2 2 2 Dosage Unit: mg/kg/day 926 67 4 966 79 2 832 81 2 908 76 3 68.8 7.6 1.2 3 3 3 Dosage Unit: mg/kg/day 637 93 2 335 262 298 51.6 2 215 363 240 273 79.2 3 341 444 633 538 133.6 2 290 348 381 340 46.1 3 326 18 241 130 157.7 2 10 39 20 23 14.7 3 18 181 Appendix 4 Individual Clinical Chemistry Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group. 1 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 Dose Level: 0 10.3 5.6 10.6 7.1 10.4 .21 2 6.4 1.06 2 Dose Level: 0.02 11.2 7.9 10.4 6.6 11.2 6.2 10.9 .46 3 6.9 .89 3 Dose Level: 2.0 11.1 6.5 Dosage Unit: mg/kg/day 151 5.4 109 153 6.0 113 152 1.4 2 5.7 .42 2 ill 2.8 2 Dosage Unit: mg/kg/day 152 5.5 109 153 5.4 112 160 5.6 113 155 4.4 3 5.5 .10 3 ill 2.1 3 Dosage Unit: mg/kg/day 158 5.7 110 182 Appendix 4 Individual Clinical Chemistry Data Males Day 30 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANF, POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ IU/G -------- Group: 1 105349 105350 MEAN S.D. N Dose Level: 0 0 1 0 .7 2 Dosage Unit: mg/kg/day Group: 2 105344 105347 105348 MEAN S.D. N Dose Level: 0.02 4 4 3 4 .6 3 Dosage Unit: mg/kg/day Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 105345 1 183 Appendix 4 Individual Clinical Chemistry Data Males Day 30 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NLTMBER ------ PCOAO IU/G -------- Group: 1 105366 105367 Dose Level: 0 0 4 Dosage Unit: mg/kg/day MEAN S.D. N Group: 2 2 2.8 2 Dose Level: 0.02 Dosage Unit: mgtkg/day 105364 7 105365 0 105370 3 MEAN S.D. N Group: 3 105369 3 3.5 3 Dose Level: 2.0 1 Dosage Unit: mg/kg/day 184 APPENDIX 5 IndividuaAlnimal PathologyData Covance 6329-222 3M T-6295.6 - - 185 APPENDIX 5 Individual Animal Pathology Data 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105349 DATE OF DEATH: 05/22/98 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACR STLMY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2 DATE AND TIME OF NECROPSY: 05/22/98 9:44 PROSECTOR: JILL PAUS RECORDER: WENDY CHE POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILAB ---------------------------------------------------------------------------------------------------------------- 0B SERV AT 10N S NECROPSY HISTOPATHOLOGY ------------------------------------------------------------------------------------------------------------- MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT TESTIS (TE) : -IMMATURE,-PRESENT GENERAL COMMENT (GC) -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCRFA ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), TESTIS (TE), MARROW, STERNUM (SE), BONE, STERN BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOP GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, MALE (MM), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), IL CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDY THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, COR ADRENAL, MEDULLA (MA), THYMUS (TH) ---------------------------------------------------------------------------------------------------------------- 186 APPENDIX 5 Individual Animal Pathology Data 4-WEEK CAPSULE TOXICITY STUDY WITH POTASSIUM SALT (PFOS;T-6295) PERFLUOROOCTANE IN CYNOMOLGUS SULFONIC MONKEYS ACID ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105350 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACR DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2 DATE AND TIME OF NECROPSY: 05/22/98 11:00 PROSECTOR: JILL PAUS RECORDER: DONIA MEYE POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILAB ---------------------------------------------------------------------------------------------------------------- 0 B S ER V A T 1 0 N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------- --------------------------------------------- MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT TESTIS (TE) : -IMMATURE,-PRESENT GENERAL -BONE COMMENT (GC) MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - -- - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREA ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), TESTIS (TE), MARROW, STERNUM (SE), BONE, STE BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOP GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, MALE (MM), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILE CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDID THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CO ADRENAL, MEDULLA (MA), THYMUS (TH) ---------------------------------------------------------------------------------------------------------------- 187 APPENDIX 5 Individual Animal Pathology Data 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105344 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACR DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2 DATE AND TIME OF NECROPSY: 05/22/98 10:25 PROSECTOR: DAVID SCHUETTE RECORDER: NANCY DIE POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILAB ---------------------------------------------------------------------------------------------------------------- 0B SERVA T 10NS NECROPSY HISTOPATHOLOGY ------------------------------------------------------------------------------------------------------------- GENERAL COMMENT (GC) MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT TESTIS (TE) : -IMMATURE,-PRESENT -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - -- - - - - - - - - - - - - - -- - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREA ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), TESTIS (TE), MARROW, STERNUM (SE), BONE, STE BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOP GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, MALE (MM), STOMACH, GL (ST), DUODENUM (DU), TEJUNUM (JE), IL CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDID THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CO ADRENAL, MEDULLA (MA), THYMUS (TH) ---------------------------------------------------------------------------------------------------------------- 188 APPENDIX 5 Individual Animal Pathology Data 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105347 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACR DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2 DATE AND TIME OF NECROPSY: 05/22/98 11:00 PROSECTOR: DAVID SCHUETTE RECORDER: NANCY DIE POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILAB ---------------------------------------------------------------------------------------------------------------- 0 B S E R V A T 10 N S NECROPSY HISTOPATHOLOGY ------------------------------------------------------------------------------------------------------------- LIVER (LI) : -INFILTRATE, LYMPHOPLASMACYTIC,-MINIMAL TESTIS (TE) : -IMMATURE,-PRESENT GENERAL CON14ENT (GC) -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - - - -- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREA ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), TESTIS (TE), MARROW, STERNUM (SE), BONE, STE BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOP GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), 9ALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, MALE (MM), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), IL CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDY THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ---------------------------------------------------------------------------------------------------------------- 189 APPENDIX 5 Individual Animal Pathology Data 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105348 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 22 DATE AND TIME OF NECROPSY: 05/22/98 10:19 PROSECTOR: DENNIS HOFFMAN RECORDER: DONIA MEYER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PAL24ER WEIGHER: NOT AVAILABL ----------------------------------------------------------------------------------------------------------------- 0 B S E R V A T 10 N S NECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT KIDNEY (KD) : -INFILTRATE, LYMPHOPLASMACYTIC,-SLIGHT, FOCA TESTIS (TE) : -IMMATURE,-PRESENT GENERAL COMMENT (GC) -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- -- - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), TESTIS (TE), MARROW, STERNUM (SE), BONE, STERNU BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOP GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, MALE (MM), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEE CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYM THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC)o ADRENAL, MEDULLA (MA), THYMUS (TH) ----------------------------------------------------------------------------------------------------------------- 190 APPENDIX 5 Individual Animal Pathology Data 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105345 DATE OF DEATH: 05/22/98 SEX- MALE DOSE STUDY DAY OF DEATH: 30 GROUP: 3 SACRIFICE STATUS: STUDY WEEK OF DEATH: 5 SCHEDULED, TERMINAL SACR TERMINAL BODY WEIGHT: I DATE AND TIME OF NECROPSY: 05/22/98 11:10 PROSECTOR: WENDY CHERRY RECORDER: DENNIS HOF POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILAB ---------------------------------------------------------------------------------------------------------------- 0 BSER VA T10N S NECROPSY HISTOPATHOLOGY ------------------------------------------------------------------------------------------------------------- MARROW, FEMUR (FM) : "SECTION EXAMINED; TISSUE NOT PRESENT TESTIS (TE) : -IMMATURE,-PRESENT GENERAL COMMENT (GC) -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - -- - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREA ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THY14US (TH), TESTIS (TE), MARROW, STERNUM (SE), BONE, STE BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOP GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, MALE (MM), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), IL CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDID THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CO ADRENAL, MEDULLA (MA), THYMUS (TH) ---------------------------------------------------------------------------------------------------------------- 191 APPENDIX 5 Individual Animal Pathology Data 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105366 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACR DATE OF DEATH: 05/22198 STUDY DAY OF DEATH: 30 STTMY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2 DATE AND TIME OF NECROPSY: 05/22/98 9:40 PROSECTOR: DENNIS HOFFMAN RECORDER: DONIA MEYE POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILAB ---------------------------------------------------------------------------------------------------------------- 0B SERVA T 10N S NECROPSY HISTOPATHOLOGY ------------------------------------------------------------------------------------------------------------- MARROW, FEMUR (FM) : @..SECTION EXAMINED; TISSUE NOT PRESENT LIVER (LI) : -INFLAMMATION, LYMPHOHISTIOCYTIC,-SLIGHT, F GENERAL COMMENT (GC) -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREA ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAI SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, FEMALE (MF), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), I CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), OVARY (OV), UTERUS (UT), CERVIX (CV), VAGINA THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), KIDNEY (KD), LUNG (LU), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ---------------------------------------------------------------------------------------------------------------- 192 APPENDIX 5 Individual Animal Pathology Data 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105367 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 20 DATE AND TIME OF NECROPSY: 05/22/98 9:47 PROSECTOR: DAVID SCHUETTE RECORDER: NANCY DIEDR POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABL ----------------------------------------------------------------------------------------------------------------- 0 BSE RVA T10N S NECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- KIDNEY (KD) : -INFILTRATE, LYMPHOPLASMACYTIC,-MINIMAL LIVER (LI) : -INFILTRATE, LYMPHOPLASMACYTIC,-MINIMAL -LIPIDOSIS, SUBCAPSULAR (TENSION LIPIDOSIS), GENERAL COMMENT (GC) -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), NARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT),. SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, FEMALE (MF), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), IL CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), OVARY (OV), UTERUS (UT), CERVIX (CV), VAGINA THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), LUNG (LU), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (A ADRENAL, MEDULLA (MA), THYMUS (TH) ----------------------------------------------------------------------------------------------------------------- 193 APPENDIX 5 Individual Animal Pathology Data 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105364 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 20 DATE AND TIME OF NECROPSY: 05/22/98 8:09 PROSECTOR: DENNIS HOFFMAN RECORDER: DONIA MEYER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABL ----------------------------------------------------------------------------------------------------------------- 0B SE RVA T10N S NECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT KIDNEY (KD) : -INFILTRATE, LYMPHOPLASMACYTIC,-SLIGHT ADRENAL, CORTEX (AC) : -HEMORRHAGE,-MODERATE, FOCAL -THROMBUS,-PRESENT >NOTE:>UNILATERAL MICROSCOPIC FINDINGS GENERAL COMMENT (GC) -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, FEMALE (MF), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), IL CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), OVARY (OV), UTERUS (UT), CERVIX (CV), VAGINA THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, MEDULLA (MA), TH ----------------------------------------------------------------------------------------------------------------- 194 APPENDIX 5 Individual Animal Pathology Data 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105365 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACR DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2 DATE AND TIME OF NECROPSY: 05/22/98 8:08 PROSECTOR: DAVID SCHUETTE RECORDER: NANCY DIED POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILAB ---------------------------------------------------------------------------------------------------------------- 0 B S E R V A T 10 N S NECROPSY HISTOPATHOLOGY ------------------------------------------------------------------------------------------------------------- KIDNEY (KD) : -INFILTRATE, LYMPHOPLASMACYTIC,-MODERATE LIVER (LI) : -INFILTRATE, LYMPHOPLASMACYTIC,-MINIMAL GENERAL COMMENT (GC) -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -STAINS-PERINEUM/PERIANAL; DARK RED AND MOIST - - -- - - - - - - - - - - - - - - - - - - - - - -- -- - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREA ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAI SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, FEMALE (MF), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), I CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), OVARY (OV), UTERUS (UT), CERVIX (CV), VAGINA THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), LUNG (LU), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX ADRENAL, MEDULLA (MA), THYMUS (TH) ---------------------------------------------------------------------------------------------------------------- 195 APPENDIX 5 Individual Animal Pathology Data 4-WEEK CAPSULE TOXICITY STUDY WITH PERFTUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105370 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 19 DATE AND TIME OF NECROPSY: 05/22/98 10:18 PROSECTOR: JILL PAUS RECORDER: WENDY CHERR POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABL ----------------------------------------------------------------------------------------------------------------- 0 B S E R V A T 10 N S NECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- LIVER (LI) : -INFILTRATE, LYMPHOPLASMACYTIC,-SLIGHT GENERAL COMMENT (GC) -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS ---------------- ---------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES),, GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SATIV GL, MANI)IB (SG), SKIN (SK), MAMMARY, FEMALE (MF), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), IL CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), OVARY (OV), UTERUS (UT), CERVIX (CV), VAGINA THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ----------------------------------------------------------------------------------------------------------------- 196 APPENDIX 5 Individual Animal Pathology Data 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105369 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACR DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 1 DATE AND TIME OF NECROPSY- 05/22/98 8:08 PROSECTOR: JILL PAUS RECORDER: WENDY CHER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILAB ---------------------------------------------------------------------------------------------------------------- 0B SERV AT 10N S NECROPSY HISTOPATHOLOGY ---------- -------------------------------------------------------------------------------------------------- GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - -- - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREA ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAI SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, FEMALE (MF), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), I CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), OVARY (OV), UTERUS (UT), CERVIX (CV), VAGINA THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREA ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ---------------------------------------------------------------------------------------------------------------- 197 Covance 6329-222 3M T-6295.6 APPENDIX 6 Summary and IndividuaHlormone AnalysesData Figure1 -Mean EstradioDlata - Males Figure2 -Mean EstradioDlata - Females Figure3 - Mean TriiodothyroninDeata - Males Figure4 - Mean TriiodothyroninDeata - Females NOTE: Thisappendixof thereportcontainsinformationsuppliedby Ani LyticsInc. and has been reviewedby theQualityAssuranceUnitof Ani LyticsInc. 198 Appendix 6 summary and Individual Hormone Analyses Data males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ Group: 1 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING TRIIODOTHYRONINE THYROXIN pg/mL pg/mL pg/mL 4)U/mL ng/dL 4)g/dL --------- ------- ------- ------------------- ---------------- -------- Dose Level: 0 Dosage Unit: mg/kg/day 34.86 29.20 32.03 4.002 2 38.62 17.83 28.23 14.701 2 0.00 0.00 0.00 0.000 2 2.33 3.30 2.82 0.686 2 i6O.41 119.07 139.74 29.232 2 4.01 6.84 5.43 2.001 2 Dose Level: 0.02 24.95 34.14 26.73 18.44 17.74 15.79 28.61 4.874 3 17.32 1.373 3 Dosage Unit: mg/kg/day 0.00 0.00 0.00 2.62 2.49 1.21 0.00 0.000 3 2.11 0.779 3 152.65 148.40 66.41 122.49 48.610 3 3.90 4.43 4.52 4.28 0.335 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 28.71 13.98 0.00 1.71 97.61 3.86 199 Appendix 6 Summary and Individual Hormone Analyses Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NL7MBER ------ Group- 1 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING TRIIODOTHYRONINE THYROXIN pg/mL pg/mL pg/mL , 4)U/ML ng/dL (Dg/dL --------- ------- ------- ------------------- ---------------- -------- Dose Level: 0 45.43 45.13 25.12 32.42 45.28 0.212 2 28.77 5.162 2 Dose Level: 0.02 28.17 70.25 45.95 21.98 26.58 42.65 48.12 21.124 3 30.40 10.852 3 Dose Level: 2.0 37.37 29.50 Dosage Unit: mg/kg/day 0.00 0.00 1.26 7.48 0.00 0.000 2 4.37 4.398 2 Dosage Unit: mg/kg/day 0.00 0.00 o.oo 3.07 3.65 0.80 0.00 0.000 3 2.51 1.506 3 Dosage Unit: mg/kg/day 0.00 1.41 172.31 92.99 132.65 56.088 2 148.92 176.45 67.89 131.09 56.434 3 122.38 5.55 4.21 4.88 0.948 2 5.71 4.94 3.62 4.76 1.057 3 3.60 200 Appendix 6 Summary and Individual Hormone Analyses Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ Group: I 105349 105350 MEAN S.D. N Group: 2 105344 105347 105348 MEAN S.D. N Group: 3 105345 ESTRADIOL pg/mL --------- ESTRONE pg/mL ------- ESTRIOL pg/mL ------- THYROID STIMULATING TRIIODOTHYRONINE THYROXIN I>U/mL ng/dL 4)g/dL ------------------- ---------------- -------- Dose Level: 0 33.04 32.75 25.02 18.84 32.90 0.205 2 21.93 4.370 2 Dose Level: 0.02 25.19 37.25 40.32 10.24 14.20 19.73 34.25 7.998 3 14.72 4.767 3 Dose Level: 2.0 18.16 20.12 Dosage Unit: mg/kg/day 0.00 0.00 0.73 3.57 0.00 0.000 2 2.15 2.008 2 Dosage unit: mg/kg/day 0.00 0.00 0.00 3.27 3.58 2.45 0.00 0.000 3 3.10 0.584 3 Dosage Unit: mg/kg/day 0.00 0.95 181.44 191.25 186.35 6.937 2 195.89 209.96 159.16 188.34 26.229 3 90.73 3.32 5.31 4.32 1.40@7 2 3.86 3.82 4.90 4.19 0.612 3 3.18 201 Appendix 6 Summary and Individual Hormone Analyses Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ Group: 1 105366 105367 MEAN S.D. N Group: 2 105364 105365 105370 MEAN S.D. N Group: 3 105369 ESTRADIOL pg/mL --------- ESTRONE pg/mL ------- ESTRIOL pg/mL ------- THYROID STIMULATING TRIIODOTHYRONINE THYROXIN (DU/mL ng/dL Cbg/dL ------------------- ---------------- -------- Dose Level: 0 Dosage Unit: mg/kg/day 67.67 39.27 53.47 20.082 2 24.46 27.47 25.97 2.128 2 0.00 0.00 0.00 0.000 2 2.57 3.32 2.95 0.530 2 141.93 183.46 162.70 29.366 2 4.57 3.95 4.26 0.438 2 Dose Level:'0.02 31.90 87.09 57.17 32.66 30.94 31.23 58.72 27.628 3 31.61 0.921 3 Dosage Unit: mg/kg/day 0.00 0.00 0.00 2.50 4.64 1.14 0.00 0.000 3 2.76 1.764 3 179.61 196.25 165.89 180.58 15.203 3 5.26 3.79 3.09 4.05 1.108 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 19.82 25.85 0.00 3.92 90.17 3.30 202 FigureI GRAPH - Mean EstradiolData - Males I I 203 Figure2 GRAPH - Mean EstradioDlata -Females i I 204 Figure 3 GRAPH -Mean TriiodothyroninDeata - Males I I 205 Figure4 GRAPH - Mean TriiodothyroninDeata -Females I I 206 APPENDIX 7 Covance 6329-222 3M T-6295.6 Dose Analysis NOTE: Thisappendixofthereportcontainsinformationsuppliedby theSponsor and hasbeen reviewedby theQualityAssuranceUnit of 3M. 207 Dose Analysis (tobe providedby theSponsor) Covance 6329-222 3M T-6295.6 208 NOTE: APPENDIX 8 Covance 6329-222 3M T-6295.6 Serum and Liver PFOS Level Determinations This appendix of the reportcontains information supplied by the Sponsor and has been reviewed by the Quality Assurance Unit of 3M. 209 Serum and Liver PFOS Level Determinations (tobe provided by the Sponsor) Covance 6329-222 3M T-6295.6 210 APPENDIX 9 CellProliferatiEovnaluation Covance 6329-222 3M T-6295.6 NOTE: Thisappendixofthereportcontainsinformatiosnuppliedby Pathology AssociatesInternationanld hasbeen reviewedby theQualityAssuranceUnit of PathologyAssociatesInternational. 211 Covance 6329-222 3M T-6295.6 CellProliferatiEovnaluation (tobe providedby PathologyAssociateIsnternational) 212 PathologyAssociateslntemational A CompanyofSciencAepplicatilontsemational Corporation An &npbymkhwad Caqmy DRAFT CELL PROLIFERATION REPORT 4-WEEK L CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295)IN CYNOMOLGUS COVANCE STUDY NUMBER 6329-222 SULFONIC MONKEYS ACID PREPARED FOR: 3M TOXICOLOGY SERVICES BUILDING 220-2E-02,3M CENTER ST. PAUL9 MN 55144-1000 PREPARED BY: PATHOLOGY ASSOCIATES INTERNATIONAL 15 WORMANIS MILL COURT, SUITE I FREDERICK, MD 21701 SEPTEMBER 30, 1998 15 Worman's Mill Court, Suite I Frederick, Maryland 21701 (301) 663-1644 (301) 663-8994 FAX DraftCellProliferatRieopnort CovanceStudyNumber6329-222 Page2 CELL PROLIFERATION REPORT 4-WEEK SULFONIC CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS; T-6295)IN CYNOMOLGUS MONKEYS COVANCE STUDY NUMBER 6329-222 PURPOSE Thepurposoefthestudywas toproviddeatafordeterminianngestimatmeadximum-tolerated dose and lower dose levelstobe used ina chronictoxicitsytudyand to assesstheeffectof thetest materialon criticaelnzyme levelsh,ormones,and otherselectebdiochemicalparameters. This report,submittedby PathologyAssociatesInternation(aPlAI)tothestudySponsor,3M, representtshecellproliferatifoinndingsand interpretatifoonrCovance Study Number 6329-222 entitle"d4-Week CapsuleToxicityStudy with PerfluorooctanSeulfonicAcid Potassium Salt (PFOS; T-6295)inCynomolgus Monkeys". Allaspectsof thetasksassociatewdithPAI's portion of thisstudy were conductedin compliancewith the EnvironmentalProtectioAngency Good LaboratoryPractic(eGLP) Regulationass setforthin Title40 of the US Code of Federal RegulationsP,art792, issuedNovember 29, 1983 (effectiDvecember 29, 1983),and with any applicableamendments. MATERIALS AND METHODS Tissue Collection for Cell Proliferation Two animalsper sex in controlgroup 1, ffi= animalsper sex in dose group 2 (0.02 mg/kgtday) and one animalpersexindosegroup 3 (2.0mg/kgtday)were sacrificeadfterfourweeks on diet. A representatisvaempleofthelivert,estes(malesonly)and pancreasfrom eachmiimalwas fixed in zinc formalin,processedand embedded to paraffinblock by Covance per protocol specificationTsi.ssueblockswere thenshippedto PAI forsectioninagnd staining.From each block, a slidewas preparedfor H&E evaluationand immunohistochen-dcdaeltectionof proliferaticnegllnuclearantigen(PCNA), a markerof cellproliferation. Immunohistochemistry for Cell Proliferation Sectionsof paraffin-embeddetdissuewsere cutat5 gm and placedon positivelcyhargedslides (SuperfrosPtlus,FisherScientifiPci,ttsburghP,A) to ensureadhesionduringprocessingfor PCNA. Standardimmunohistochemicamlethods were used to staintissuesforPCNA (PAI's StandardOperatingProcedureforImmunohistochemicaSltaining(SOP #707). Briefly,tissue sectionwsere incubatedwitha monoclonalantibodytoPCNA (DAKO, lot#016,PAI No. A1723) and reagentsrequirefdortheavidin-biotpienroxidase(ABC Kit,lot#PK-6 100,PAI No. K 324) method forthedetectioonftheantigen-antibocdoymplex. PCNA expressionincellswas localized by thechromagen 3,3-diaminobenzidin(eDAB; Sigma ChemicalCo., lot#18H8201). Tissue sectionswere counterstainewdithhematoxylin. Cell Proliferation Measurements The percentageof proliferaticneglls(proliferatiinngdex,PI) was determinedby scoringat least 3000 hepatocytesin 10 fieldosf livera,tleast500 Leydig cellsof theteste(smalesonly),and at least2000 acinarcellsof thepancreasper animal.A negativecontrolslidewas includedin the staininrgun and consistedofstudyfissuethatwas notincubatedwiththeprimaryantibody. Draft CEIIProliferatioRneport Covance Study Number 6329-222 Page 3 For ceflproliferatieovnaluationsl,ideswere firspterusedatlow magnificatio(nIOOX) tojudge qualityof stainingp,rocessingand sectioningp,otentiaplatternsof cellulaprroliferatioann,d histomorphologicchanges. Cellproliferatiwoans thenquantifieadt highermagnificatio(n20OX forlivera,nd 40OX fortesteasnd pancreas)as describedabove. Histomorphologywas further assessedby evaluatintgheH&E slidepreparedfrom thesame tissueblockfor each animal evaluatedforcellproliferation. Statistical Analysis Due to the small sample size, statisticalanalysis was not performed. RESULTS Cell Proliferation Individual animal cell proliferation data are presented in Section I[[(Table 1). CeE proliferation in the liver,testesand pancreas of controland testmaterial-treatedanimals was similar. Histopathology Sections from the same tissueblocks used for prepar-ationof PCNA-stained slides were stained with hematoxylin and eosin (H&E) for histopathologicevaluationto facilitattehe interpretatioonf the immunostained slides.Individualanimal findingsare presented in Appendix 1. Single sectionsof liver,pancreas, and testesfrom 6 young adult male monkeys and single sections of liverand pancreas from 6 young adult female monkeys representingcontrol,low-dose (0.02 mg/kg/day), and high-dose (2.0mg/kg/day) treatment groups were evaluatedhistologically.Each tissuesectionwas stainedwith hematoxyhn and eosin. The purpose of this evaluationwas to detenriinewhether or not morphologic changes were occurring in these tissueswhich may alteror confound the specificitoyf the PCNA stainingobserved in these animals. The resultsshowed thatno significantchanges were observed in eitherthe liver,pancreas, or testiculatrissuesfrom male monkeys or the liverand pancreas tissuesfrom female monkeys, which would alterthe interpretatioonf the PCNA stainingin thisstudy. DISCUSSION In:the present study, cellproliferatiownas measured within the liver,testesand pancreas of male monkeys, and the liverand pancreas of female monkeys from control (0 mg/kgtday), low dose (0.02 mg/kg/day), and high dose (2.0 mg/kg/day) groups afterfour weeks on study to determine an estimated maximun-tolerated dose and lower dose levelsto be used in a chronic toxicitystudy and to assess the effectof the testmaterialon criticaelnzyme levels,hormones, and other selected biologicalparameters, to includecellproliferation. There did not appear to be a cellproliferativreesponse to the testmaterial in the liver,testesor pancreas, as determined by proliferatinigndiceswhich were similarin allanimals. SUMMARY In the present study,cellproliferationa,s determined by measuring the proliferatingindex,was not increased in the liver,testesor pancreas of monkeys. DraftCellProliferatioRneport Covance Study Number 6329-222 II.TABLE COVANCE STUDY NO. 6329-222 TABI F 1.CELL PROUFERATION IN MONKEYS Group Sex 1 - 0 mg/kg/day (Control) m 1 - 0 mg/kg/day (Control) m 2 - 0.02 mg/kg/day (Low dose) m 2 - 0.02 mg/kg/day (Low dose) m 2 - 0.02 mg/kg/day (Low dose) m 3 - 2.0 mg/kq/day (High dose) m 1 - 0 mg/kg/day (Control) F 1 - 0 mg/kq/day (Control) F 2 - 0.02 mg/kg/day (Low dose) F 2 - 0.02 mg/kglday (Low dose) F 12 - 0.02 mg/kg/day (Low dose) F 13 - 2.0 mg/kq/day (Highdose) F Animal Number 105349 105350 105344 105347 105348 105345 105366 105367 105364 105365 105370 105369 Proliferating Index Liver 0.025% 0.087% 0.056% 0.298% 0.106% 0.026% 0.000% 0.086% 0.000% 0.083% 0.143% 0.000% Proliferating Index Testes 20.3% 22.9% 18.5% 33.6% 16.5% 17.6% NA NA NA NA NA NA Proliferating Index Pancreas 62.30% 50.30 66.30% 55.50% 63.90% 44.90% 50.20% 65.60% 39.60% 43.60% 60.20% 40.90% I DraftCellProliferatioRneport Covance Study Number 6329-222 APPENDIX I I Covance Study Number 6329-222 IndividualAnimal HistopathologyFindings- Male Monkeys 4-week Capsule ToxicityStudy Animal Number .105349 -105350 105344 -105347 -105348 1053.45 Liver Testes Pancreas No signiicantfindings No signicant ndinas INo sipi icantfindings No significafnitndings No significafnitndings No significamnntdings No significafnitndings No significafnitndings No sign.ificafnitndings No signiicantfindings No significafnitndings No si cantfindings - No significafnmtdings No significafnitndings No significafnitndings - No significafnitndings No significeLERI!ng No significafnitndipzs IndividualAnimal HistopathologyFindings - Female Monkeys 4-week Capsule ToxicityStudy 105366 -105367 105364 105365 105370 105369 Animal Number Liver I No significafnitndings No significafnitndings No significafnitndings No significafnitndings No significafnitndings No significafnitndings Pancreas I No significanntdings No significafnitndings No sii-nificfainntdings No significantdings No significafnitndings No significafnitndings DraftCellProliferatiRoenport Covance Study Number 6329-222 111.SIGNATURE PAGE 4-Week Capsule ToxicityStudy with PerfluorooctaneSulfonicAcid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys (Covance Study Number 6329- 222) Submittedby: PAI ProjectManager: Sandra R. Eldridge,Ph.D. Date PAI ProjectPathologist: CarolynMc@yer,D.V.M., f)iplomateA,.C.V.P. Date DraftCellProliferatiRoenport Covance StudyNumber 6329-222 IV. QUALITY ASSURANCE STATEMENT