Document ZnVdk9RZqap6y10Re0eJJV0G7

DraftReport 26-Week Capsule ToxicityStudy with PerfluorooctanSeulfonic Acid PotassiumSalt(PFOS; T-6295) in Cynomolgus Monkeys PREPAMD FOP, 3M COVANCE STUDY NUMBEP6329-223 VOLUME IOfn COVAW'C-E.-"'\ IM DEWSLOPMIWT SEMCU COMPANY Sponsor. 3M St.PauL Minnesota UNAUDrrED DRAFR April12,2000 FINAL REPORT Study Tide: 26-Week CapsuleToxicityStudywithPerfluorooctanSeulfonicAcid PotassiumSalt(PFOS; T-6295) inCynomolgus Monkeys Author. PeterJ.Thomford, PhD Study Completion Date: To be determined TestingFadlity: Covance LaboratorieIsnc. 3301 Kinsman Boulevard Madison,Wisconsin 53704-2595 Laboratory Study Identification: Covance 6329-223 SponsorStudy Identification: 3M StudyNo. T-6295.7 Volume IofH Page I of 821 Covance 6329-223 3M T-6295.7 CON[PLL4,NCE STATFIAENT 26-Week Capsule ToxicityStudy withPerfluorooctaneSulfonicAcid Potassium Salt(PFOS; T-6295) inCynomolgus Monkeys Allaspectsofthisstudywere inaccordancewiththe EnvironmentalProtectionAgency Good LaboratoryPracticeStandards,40 CFR 792. PeterJ.Thomford, PhD Study Director Covance LaboratoriesInc. Andrew M. Seacat,PhD Study Monitor 3M Date Date 2 Comee 6329-223 3M T-6295.7 STUDY ATION 26-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid PotassiumSalt(PFOS; T-6295) inCynomolps Monkeys Test Material PerfluorooctaneSulfonicAcid Potassium Salt(PFOS; T-6295) Sponsor 3M Toxicology Services Building220-2E-02,3M Center SL PauL Minnesota 55144- 1000 Study Monitor Andrew M. Seacat,PbD 3M 651.575.3161 AlternateStudy Monitor Marvin T. Case,DVK PhD 3M ToxicologyServices 651.733.5180 Study Location Covance LaboratoriesInc. 3301 Kinsnum Boulevard Madison, Wisconsin 53704-2595 Study Director PeterJ.Ihomford, PhD Covance LaboratoriesInc. PO Box 7545 Madison, Wisconsin 53707-7545 608.241.7207 Study Timetable Study InitiatioDnate In-Life(ExperimentalS)tartDate In-LifeTerminationDate ExperimentalTerminationDate August 20, 1998 August 26, 1998 March 7,2000 To be detemiined 3 Covanc6e329-223 3M T-6295.7 KEY PERSONNEL 26-WeekCapsuleToxicitSytudywithPerfluorooctSaunlefoniAccid Potassium Salt(PFOS; T-6295) inCynomolgus Monkeys Study Director Study Toxicologist Study Coordinator Ulamger, Large Animal Toxicology Supervisor,'DosFeormulation' AssociateDirector,LaboratoryAnimal' Medicine ClinicalPathologist Supervisor,ClinicalPathology Anatomic Pathologist Supervisor,Anatomic Pathology Supervisor,Anatomic Pathology Consultant PeterJ.lbomford, PhD Dale Aldridge,Bs ElizabethA. Disch,BA SharonDunn, LATG, AT DixieBushee,BS, LATG Donna J.Clemons, DVM, Ms Diplomate,ACLAM RobertL HalL DVK PhD Diplomate,ACVP (ClinicaPladmlogy) Ronald Markevitch,BS, MT (ASCP) RobertA. Leedle,DVK PhD Diplomate,ACVP LaurieJ.SchullerB,A, LAT Kimberly W. Durland,BS, HT StephenL Bistner,DVM Diplomate,ACVO VeterinaryOphdmlrmlogist 4 Covmcc 6329-223 3M T-6295.7 VOLUME I OF H CONTENTS Page ABSTRACT ............................................................................. PURPOSE ...................................................................1..2............... REGULATORY coupLLkNCE ..................................................1..2............. TEST MATERIAL, VEIHCLE, AND SOLVENT ............................-......1.2.......... Test Material..................................................................-..1...2........... Vehicle........................................................................1..2............ Solvent.................................................................1.3........... GelatinCapsules........................................................-.1.3........... Reserve (Archive)Samples ................................................1.3........... Dispositio.n.................................................................1..3............ TEST ANIMALS AND HUSBANDRY ....................................-.-.-.-..1.3.......... Animals................... ..............1..3 Identificati.o.n...............................................................1..4........... Justificati.o.n...........................................................1.4........... Husbandry ...........................................................-...1.4........... Acclimation.............................................................1.5........... PROCEDURES .....................................................................1.5.......... Group Designations and Dosage Levels...................................-.-.-..-.i.s......... Dosing Procedures........................................................1.6.......... Dose Analyses...........................................................1.7........... Observationof Animals ................................................-...1..7........... ClinicalPathology........................................................1.8.......... Blood Hormone Determination...................................................1..9............ Serum PFOS Level Determination...........................................19........... AdditionalSerum Collection...............................................2.0.......... Urine and Feces PFOS Level Determination.................................-.2..0.......... AdditionalFecal Samples ..................................................20........... InterimLiverBiopsy Samples ..............................................2.0.......... Terminal LiverBiopsy Samples .............................................21........... Anatomic Pathology- Temiinal Sacrific.e....................................21........... Anatomic Pathology - Recovery Sacrific.e....................................24........... StatisticAanlalyses.......................................................2.5.......... Record Retention.........................................................2.5.......... 5 777 Covance 6329-223 3M T-6295.7 CONTENTS (Continued) VOLUME I OF H Page RESULTS AND DISCUSSION ............................................2.6........... Observationof Animals................................................2.6........... ClinicaPlathology....................................................2.8........... PahnitoylCoA OxidaseDeterminatio.n...................................2.8........... Blood Hormone Determinatio.n..........................................2.8........... Anatomic Pathology...................................................2.9........... CONCLUSION ........................................................3.0........... SIGNATURES ........................................................3.1........... REFERENCES .........................................................3.2........... OPHTHALMOLOGY REPORT ...........................................3.3........... PATHOLOGY REPORT .................................................3.4........... CONCAF.NTS ON THE DATA ............................................4.1........... CODES, ABBREVIANONS, AND UNITS ...................................4.3........... GeneralCodes and Abbreviation.s........................................4.4........... Codes forClinicaPlathology............................................4.5........... Abbreviationasnd UnitsforClinicaHlematology............................4.8........... AbbreviationasndUnitsforClinicaClhemistry..............................5.0........... Abbreviationasnd UnitsforClinicaUlrinalysi.s.............................5.2........... Codes forAnatomicPathology...........................................5.3........... FIGLTRES I Mean Body Weight Data-Treatment...................................5.5........... 2 Mean Body Weight Data-Recovery....................................5.6........... TABLES I Summary ofClinicaOlbservation-sTreatment...........................5.7........... 2 Summary ofClinicaOlbservation-sRecovery(Days 186through365)........6.1...... 3 Summary ofClinicaOlbservation-sRecovery(Days366 through561)........6.2...... 4 Sununary ofOphthalmicObservation-sTreatment........................6.4........... 5 Sununary of OphdiahnicObservations-Recovery.........................6.6........... 6 Summary ofBody WeightData (kg)-Treatment..........................6.7........... 7 Surmnary ofBody WeightData (kg)-Recovery..........................7.2........... 8 Summary ofClinicaHlematologyData -Day -27.........................8.0........... 9 Summary ofClinicaHlematologyData -Day 37 ..........................8.4........... 10 Surmnary ofClinicaHlematologyData -Day 62 ..........................8.8........... II Summary ofClinicaHlematologyData -Day 91 ..........................9.2........... 6 Covance 6329-223 3M T-6295.7 VOLUME I OF H CONTENTS (Continued) Page TABLES 12 Summary of ClinicalHematology Data - Day 153 ............................9.6............ 13 Sununary of ClinicalHematology Data -Day 182 ...........................1.0.0............ 14 Summary of ClinicalHematology Data -Day 217 ...........................1.0.4............ 15 Sumnimy of ClinicalHematology Data - Day 245 ...........................1.0.8............. 16 Summary of ClinicalHematology Data - Day 274 ...........................1.1.2............ 17 Summary of ClinicalHematology Data - Day 322 ...........................1.1.6............ 18 Summary of ClinicalHematology Data - Day 364 ...........................1.2.0............ 19 Summary of ClinicalHematology Data -Day 456 ...........................1.2.4............ 20 Surmiary of ClinicalHematology Data -Day 546 ...........................1.28............. 21 Summary of ClinicalChemistry Data - Day -27.............................1.3.2............ 22 Sunmury of ClinicalChemistry Data - Day 37 .............................1.3.8............ 23 Summary of ClinicalChemistry Data - Day 62 ..............................1.44............ 24 Summary of ClinicalChemistry Data - Day 91 ..............................1.5.0........... 25 Summary of ClinicalChemistry Data - Day 153 ............................1.5.6............ 26 Sununary of ClinicalChemistry Data - Day 182 ............................1.6.2............ 27 Sununary of ClinicalChemistry Data - Day 217 .............................1.68............ 28 Sumnwy of ClinicalChemistry Data - Day 245 .............................1.7.4........... 29 Summary of ClinicalChemistry Data -Day 274 ............................1.8.0............ 30 Summary of ClinicalChemistry Data -Day 322 ............................1.8.6............ 31 Sununary of ClinicalChemistry Data - Day 364 ............................1.9.2............ 32 Surmnary of ClinicalChemistry Data - Day 456 ............................1.9.8............ 33 Sumnuwy of ClinicalChemistry Data - Day 546 ............................2.0.4............ 34 Surmnary of ClinicalUrinalysisData - Day -27 .............................2.1.0............ 35 Summary of ClinicalUrinalysisData - Day 37 .............................2.1.2............ 36 Sumnwy of ClinicalUrinalysisData - Day 62 .............................2.1.4............ 37 Summary of ClinicalUrinalysisData - Day 91 .............................2.1.6............ 38 Summary of ClinicalUrinalysisData - Day 153 ............................2.1.8............ 39 Summary of ClinicalUrinalysisData - Day 182 ............................2.2.0............ 40 Sununary of ClinicalUrinalysisData - Day 217 ............................2.2.2............ 41 Summary of ClinicalUrinalysisData -Day 245 ............................2.2.A............ 42 Summary of ClinicalUrinalysisData -Day 274 ............................2.2.6............ 43 Summary of ClinicalUrinalysisData - Day 322 ............................2.2.8............ 44 Summary of ClinicalUrinalysisData - Day 364 ............................2.3.0............ 45 Summary of ClinicalUrinalysisData - Day 456 ............................2.3.2........... 46 Summary of ClinicalUrinalysisData -Day 546 ............................2.3.4........... 47 Summary of PaknitoylCoA Oxidast Determinations........................2.3.6............ 48 Summary of Organ Weight Data ..........................................2.3.8........... 7 Covance 6329-223 3M T-6295.7 VOLUME I OF H CONTENTS (Continued) Page TABLES 49 Incidenceof Macroscopic Observations- TerrrAnalSacrifice..................2.68.......... 50 Incidenceof Macroscopic Observations- Recovery Sacrifice.................2.7.1......... 51 Incidenceof Microscopic Observations- Terminal Sacrific.e.................2.7.2.......... 52 Incidenceof lvficroscopiOcbservations -Recovery Sacrifice.................2.8.2.......... APPENDIX I................................................................2.8.3............. ProtocolDeviations........................................................2.8.4............. Protocol..................................................................2.8.8............. ProtocolAmendment No. I .................................................3.0.6............. ProtocolAmendment No. 2 ..................................................3.1.5............. ProtocolAmendment No. 3 .................................................3.2.3............. APPENDIX 2 ...............................................................3.2.9............. IndividualAnimal Fate Data .................................................3.3.0............ IndividualClinicalObservations.............................................3.3.2............. IndividualOphthalmic Observations..........................................4.7.4............. APPENDIX 3 ...............................................................4.8.9............. IndividualBody Weight Data (kg)...........................................4.9.0............. VOLUME H OF H APPENDIX 4 ...................................................................................5..(..X...................... IndividualClinicalHematology Data .........................................5.0.5............. IndividualClinicalChemistry Data ...........................................5.6.5............ IndividualClinicalUrinalysisData ...........................................6.3.7............. APPENDIX 5 ...............................................................6.8.5............. IndividualPahnitoyl CoA Oxidase Determinations.............................6.8.6............ IndividualAnatomic Pathology Data .........................................6.9.0............ APPENDIX Sumnwy 6 ...............................................................7.6.9............. and IndividualBlood Hormone Determination........................7.7.0............ APPENDIX 7 ...............................................................8.0.8............ Cell ProliferatioRneport ...................................................8.M............. 8 ABSTRACT Cmuce 6329-223 3M T-6295.7 7be purpose of thisstudywas toassesstheeffectof thetestmaterialP,erfluorooctane SulfonicAcid PotassiumSalt(PFOS; T-6295 (hereafterrefumd to asPFOS)] on critical enzyme levels,hormones, and otherselectedbiochemicalparameterswhen administered dailyby oralcapsuleto cynomolgus monkeys foratleast26 weeks. The treatmentperiod was fbuowed by an approximate52-week recoveryperiod. Male and femalecynomolps monkeys were assignedtofourgroups(sixanfinawsex in Groups 1,3,and 4;fouranimawsex inGroup 2). Each group receiveddose preparations containingthe vehicle,lactoseo,r 0.03,0.15,or 0.75 mg ofPFOS/kg ofbody weigbt/day (mg/kgtday).Two animaldgroup inGroups 1,3,and 4 were ina recoveryperiodand were not treatedforatleast52 weeks fbllowingthe 26 week treatmentperiod. Food was providedad libiturne,xceptwhen animals were fasted.Water was provided -adlibitum The animalswere observedtwicedaily(am and p.m) forrnoftalkyand moribundity.At leastonce daily,animalswere examined forabnormalitieasnd signsof toxicitya,nd food consumptionwas assessedqualitativelyO.phthahnic examinations were done beforeimtl-itionftreatmentand duringWeeks 26 and 52. Body weight data were recordedweekly beforeinitiationf atatinento,n Days -I and 1,and weekly thereafterB.lood and urinesamples were collectedforclinicahlematology,clinical chemistry,and urinalysitsestsbeforeinitiatioonfhvwmnt and atspecifiedintervals duringtreatmentand recovery.Blood was alsocollectedforblood hormone and PFOS leveldeterminationsbefore,during,and afterftatmnt atspecifiedintervalsF.eces and liversamples were alsocollectedatspecifieidntervalsO.n Day 155 (Week 23), one nale given 0.75 mg/kglday died,and on Day 179 (Week 26),one male given 0.75 mglkgtday was sacrificeddue topoor health.On Days 184 and 185 (Week 27), fouraninmls/sex/grou(pGroups I through3) and fourfemalesand two males (Group 4) were anesthetizedw,eighed,exsanpinated,and necropsied.At necropsyatthe scheduledand unscheduled sacrificesa,serum sample was collectedm,acroscopic observationswere recorded,selectedorgans were weighed, and selectedtissueswere collectedand preserved.Nficroscopicexaminationswere done on tissuesfrom each animal inthecontroland high-dosegroups and selectedtissuefsrom animalsinthe lowand mid-dose groups. Tissueswere alsocohectedforpahwtoyl CoA oxidase determinationc,ellprolffemtionevaluationP,FOS determinationa,nd electron microscopy. Additionallyt,hebilewas collectedfrom thegallbladdera,nd the gallbladderwas preserved.At therecoverysacrificoen Day 549, theremainingGroup 4 9 CANmce 6329-2Z 3M T-6295.7 mffinalswere anesthetizedw,eighed, exsanpinated, and necropsied.Macroscopic observationswere recorded and specifiedtissuesand serum were coileded. Remaining animals in Groups I and 3 were donated or mmferred to a follow-upstudy, Covance 6329-268. At alldose levels,clinicalobservations,o,phfthnic observations,and pahnitoyl CoA oxidase determinationsdo not appear to be affectedby treatmentwith PFOS. Two males given 0;75 mgvday died during treatment.These deathswere preceded by some adverse clinicalobservations(constrictedpupil palegums, abnormal feces, excessivesalivationl,abored respirationd,ehydrated appearance,hypoactive,ataxic, recumbent, low fbod consumption) and appeared to be relatedto the atiniiniqmdonof PFOS. When compared with aninvas given the controlmaterial covariateadjustedmean body weights (CAM formales given0.75 nig/Wday were slightllyower beginningat Week 21, and forfemales given 0.75 mg/kgtday CAM body weights were, ingeneral significantllyower beginning atWeek 11. Similardecreaseswere not seen inthe otha treatedgrouos;thereforet,hisfindingislikelytestmaterial-relatedT.est material-related effectson body weights were not apparentduringrecovery. Low fbod ednsumption was noted sporadicallyforanimals in thegroups given thecontrolmaterialand 0.03 mglkgtday throughout treatment.The incidenceof low fbod consumption was generallyhigher inthe groups given 0.15 or 0.75 mg/kgtday as compared to anhiws given thecontrolmaterialand appeared to be testmaterial-relatedD.uring recovery, effectson food consumption were reversed. Estradiolvalues were generallylower on Days 62, 91, and 182 inmales given 0.75 mgtkgtday, although because of the variationin the dataonly the Day 182 value was significantE.strone valueswere generallyhigherin allof thetreatedfemaleson Days 37, 62, and 91, although because of the variationin the datanone of thesevalues were significantldyifferenta,nd thisdifferencewas not apparenton Day 182. Triiodothyroninevalueswere notablylower in both males and females given 0.15 and 0.75 mg/kgtday on Days 91 and 182. With the singleexceptionof nmles given 0.15 mg/kgtday on Day 9 1,allvalueswere significantllyower. During recoverywere occasionalinstancesin which thehormone valuesin treatedgroups differedslightlyfrom those of controls,but those differenceswere not consistentover time or between sexes, were not clearlydose-related,and did not appear to be clearlyrelatedto the administrationof thetestrmterial Apparent differencesinthe sexualmaturityof both males and females used inthisstudy complicates the interpretatioonf the hornione data. 10 Covance 6329-223 3M T-6295.7 The only clinicalpathology parameters considered relatedto the testmaterialwere lower totalcholesterolfor animals given 0.75 mg/kg/day and lower high density lipoprotein cholesteroflbranimals given 0.15 or 0.75 mg/kgtday. These effectswere reversedwithin thefirs5t and 9 weeks ofrecovery,respectively. At theterminalsacrificei,ncreasedliverweights,macroscopicobservationsof mottled liverh,epatocellulahrypertrophy,and hepatocellulavracuolationinanimalsgiven 0.75mg/kgtday were consideredrelatedtoPFOS fteatment.However, the microscopic examinationliverbiopsiestaken duringrecoverydid not indicateany testmaterial-related findingsand none ofthe macroscopic observationsmade attherecoverysacrificweere consideredtestmaterial-relateTdh.ere were no microscopicfindingsinthe Ever from the animalsinthe high-doserecoverygroup. This indicatetshatthehepatictest material-relateedffectswere reversible. Treatment withPFOS by oralcapsuleforatleast26 weeks isgenerallyweh-toleratedin male and femalecynomolgus monkeys atdosesup to 0.15 mg/kg/day. Clinicaland pathological'findincgosnsideredtobe associatedwith thetreatmentof PFOS afterat least26 weeks of treatmentwere found tobe reversibldeuringa 52-week recovery period.Based on thedatapresentedinthisreport,the no-observable-effelcetvelis 0.03 mg/kg/day. Dose analyses(providedby the Sponsor)and electronmicroscopy result(sprovidedby PAI) areforthcoming. PURPOSE Covance 6329-223 3M T-6295.7 7be purpose of thisstudy was to assessthe effectof the testmaterialon criticaelnzyme levels,hormones, and otherselectedbiochemicalparameterswhen administereddailyby capsuleto cynomolgas monkeys f6ratlent 26 weeks. The treatmentperiodwas followedby an approximate52-week recoveryPeriod. REGULATORY CON[PLLANCE All aspectsofthisstudywere done inaccordancewith theEnvironmentalProtection Agency Good LaboratoryPracticeStandards,40 CFR 792. TEST MATERL41,s VEE[ICLEs AND SOLVENT Test Mateirial The testmaterialPerfluorooctaneSulfonicAcid Potassium Salt(PFOS; T-6295), LOt No. 217, isa whitetooff-whitepowder. Itwas receivedatCovance on September 4, 1997. 'Me testmaterialwas storedatroom temperature. Informationon synthesismethodl% stabilitpyu,rity,composition,or othercharacteristics thatdefinethetestmaterialison filewith the Sponsor. Vehicle The vehiclewas lactose(Spectrum,New Brunswick,New Jersey)L,ot No. NNO192 (expiratiodnateFebruary 13, 1999). Itwas receivedatCovance on March 30, 1998. The vehiclewas storedatroom temperature. Informationon synthesismethods, purity,stabilitcyo,mposition,or othercharacteristics thatdefinethevehicleison filewith the manufacturer. 12 Covanc6e329-223 3M T-6295.7 Solvent The solvenwtas aceton(eSpecnM GardenaC,alifoniiLao)t,No. LHO253,(exphudon dateJune 2000). Itwas receivedatCovance on June 23, 1997. The solventwas storedat room temperature. Inforimtionon synthesismethods, conipositiono,r othercharacteristitchsatdefme the solventison filewiththe manufacturer. GelatinCapsules Gelatincapsules,SizeNos. 2 (LotNo. 122932,expiratiodnateJune 12,2003) and 4 (Lot No. 544043, expiratiodnateAugust 1,2002) were manufacturedby Torpac Inc, (FairfielNde,w Jersey).Lot No. 122932 was receivedatCovance on June 12, 1998,and Lot No. 544043 was receivedon September I and November 11, 1998. The capsules were storedatroom temperature.A copy of theCertificatoefAnalysisprovidedby the manufacturerismaintainedin the data. Reserve (Archive)Samples A reservesample (I g) ofeach lotofthe testniaterialvehiclea,nd each test materiavlactosedilutionwas taken and stomd atroom temperature.These samples were transferretdothe Sponsor aftercompletionof thetreatmentphase (seeProtocol Deviatiom). Disposition Remaining testmaterialwillbe retainedatCovance foruse inpossiblefuturestudies. TEST AND4ALS AND HUSBANDRY Animals Young adulttoadultcynomolgus monkeys were obtainedfrom Covance Research ProductsInc.(Denver,Pennsylvania)on June 30, 1998. "fbewiinws weighed .2.4to4.4kg atinitiatiofntrament. 13 Covance 6329-223 3M T-6295.7 Identification Each animal was assigned a permanent number upon arrivaland identifiedwith a col[2r tag beforeinitiationftreatmenl Alldataforan animalarerecordedunder thisnumber. Justification PPOS isa known hepaticperoxisomeprorferatorCPP) inthemL When exposed toa PP, nonhuman primates(such asthe cynomolgus monkey) respond similarlytohumans (Le.,low tono hepaticresponse)and therefbrearean appropriatehuman surrogate species. Husbandry Animal Rooms 251 and 259 were used for thisstudy. Envirommental controlsforthe animal rooms were settomaintain18 to 29 *C, a relativheumidity of30 to 70%, and a 12-hourlight/12-houdrark cycle.Variationsfrom theseconditionsare documented in the dataand'areconsideredto have had no effecton theoutcome ofthe study. The animalswere housed individualliynsuspended,stainless-steceaige& Certifiepdrimatediet(#8726C, Harlan Teklad)was providedonce ortwicedaily,unless otherwisespecified.The lotnumbers arerecordedinthedata. The dietisroutinely analyzedby themanufacturerfornutritionaclomponents and environmental contaminants.Resultsof specifiednutrientand contaminantanalysesareon fflewith Covance-Madison. FTuitsor additionaslupplementswere provided,but did not require analysis. Water was provided ad libitum.Samples of thewater areanalyzed forspecified microorganisms and environmentalcontaminants.The resultsareon filewith Covance-Madison. There were no known contaminantsinthe dietor water atlevelsthatwould have interferewdith thisstudy. 14 Covanc6e329-223 3M T-6295.7 Acdihnation Twenty-fbumralesand24 femalewserereceiveodn June30,1998,andaccumted in Animal Room 251 fbr57 days beforeinitiatiofntreatment.In general Animal inthis slupmentappearedhealthy Dunng acclunauon,theannnalswere exammed for abnormalitieisndicativoef healthproblems. Inadditiont,hreetuberculositsestsa, physicalexamination,and a fecalflotatiofnbrparasitewsere perfornra on each sknimal PROCEDURES This studywas conducted inaccordancewith theProtocoldatedAugust 20, 1998, and ProtocolAmendment Nos. 1,2,and 3. The protocolprotocolamendments, and protocol deviationsare inAppendix 1. Group Designationsand Dosage Levels Selectionof animalsforthestudywas based on datacollectedduringacclimation. Animals were assignedtotreatmentgroups usinga computerizedblockingprocedure designedto achievebody weight balancewith respecttotreaunentgroup. Group I 2 3 4 Dose Level (mg/kg/day)a w 0.03 0.15 0.75 TotalMaterialDose Level (nWAg/day)b 30a 15b 6c 30c Number Males 60 4 6d 6d of Aninmls Females ;34 6d 6' a The controlgroup (Group 1)receivedthe equivalentamount of lactosein gelatincapsulesas thetotalmaterialadministeredto Group 4. b The low-dose (Group 2) receivedthe testmaterialdilutedwith lactose (1:499,w:w). c The mid-dose (Group 3) and high-dose(Group 4)groups receivedthetest materialdilutedwith lactose(1:39,w:w). d Two animals inGroups 1,3,and 4 designatedas recoveryanimalswere treatedforatleast26 weeks, thentreatmentwas discontinueda,nd the animals were observed forreversibilitpye,rsistenceo,r delayedoccurrence oftoxiceffectsforatleast52 weeks posttreatimnl 15 Covanc6e329-223 3M T-6295.7 DosingProcedures VeNde. Dose levelwserebasedon thevehiclaessuppliefdorGroup1.FbrGroupI dose preparationst,hespecifiedamount of lactosewas weighed, =mfared intogelatin capsules,and thetop and bottom halvesof each capsulewere joined.Capsuleswere prepared atleastonce weekly. Test MateriaL The testmatedaylactosepreparationsforGroups 2 tbrough4 were . dilutedonce beforeinitiationf awtnient;capsuleswere preparedatleastowe wewy. A specifiedamount of'tesmtaterialwas weighed, placedintoa labeledmixing container, and theappropriatevolume of acetonewas added. After stirrinmganually untilthetest materialwas dissolved,therequiredamount of lwose was weighed and tmwfmted todm container.The components were mixed thoroughlyusinga spatul& The preparedtest materialdilutionwas stirrepderiodicallwyhile allowed to standexposed totheairuntil the acetonehad evaporated.Preparationswere dilutedtofacilitatceapsulepreparation. Samples of thefinishedmixturefordose analyseswere taken directlfyrom thecontainer. 71bedose preparationswere storedatroom temperaturebetween capsulepreparation& The appropriateamount ofpreparedtestmaterialwas weighed and awaferred intoSize2 (Days 1 through8)or 4 (Days 9 through184) gelatincapsulesand thetop and bottom halvesof each capsulewere joined.Size4 capsuleswere used insteadof Size2 to better facilitadtoese administrationI.ndividualdailydoses were based on the mdst recently recordedbody weight,withtheexceptionof doses given on days when body weight measurements were performed;on thosedays,thepreviousbody weight was usedl AR capsulepreparationswere storedatroom temperatureuntilused fordo Method of Administration.Gelatincapsuleswere used tofacilitactoemparisonwith datafrom previoustoxicologystudiesthatused theoralroute.Also,oralisthe most likelyrouteof exposure inhumans. Partialor intactcapsuleswere noted inthevomitus of severalanimals on occasion;however, thisisnot consideredtohave adverselyaffected the resultsof the study. The dose preparationswere administeredorallyingelatincapsulesonce daily 7 days/week foratleast26 weeks (seeProtocolDeviationsforexceptions). 16 Covanc6e329-223 3M T-6295.7 DoseAnalyses HomogeneityandstabiliatnyalysewseretheresponsibiloifthyeSponsor. Samples (approximatelyI g each)were takenfrom thetop,middle,and bottom of thetest materiaulactospereparationson Day -15 forhomogeneity analysi& SamplescoRected from the middle of thepreparationswere alsodesignatedforprestudystabilitaynalysis. A setof samples (approximately1 g each)were taken from the low- and high-dosetest materiavlactospereparationsattheend ofthe treatmentphase fbrtestmaterialcontent analysis. All samples were storedatroom temperatureuntilsentunder ambient conditionsto the Sponsor foranalysis.Resultsof dose analyseswillbe providedforinclusioninthe final reporl ObservationofAnimals CHWcal Obkrvations. The animalswere observedtwicedaily(am. and p.im)for mortalityand moribundity Animals were alsoobservedatleastonce daily(anL) fbr signsofpoor healthor abnormal behavior,and food consumption was assessed qualitativeloyn;ly abnormal findingswere recorded.Once weekly and on theday of scheduledsacrifice,ach animalwas observed;abnormal findingsor an indicatioonf normal was'recorded(seeProtocolDeviationsforexceptions).Additionallyp,ostdose observationswere recorded duringtreatmentapproximately30 to90 minutesafterthe lastdose administrationo;nly abnormal findingswere recordedl Ophthalmology. Ophthalmic examinationswere done on each animal beforeinitiation of treatment,beforethescheduledterminalsacrificdeuringWeek 26, and during Week 52 (seeProtocolDeviations).The pupilswere dilatewdith 1% Mydriacyl(&and theanteriorportionofthe eye,opticmedia, and ocularfundus.wereexanu*nedwith an indirecotphthalmoscopeby a board-certifioepdhthalmlogisl Body Weights. Individuablody weight datawere recordedweekly beforeinitiatiofn treatment,on Day -1,on thefirsdtay of treatment,and weekly thereafterB.ody weights were alsorecordedforanimalssacrificeadtunscheduled intervals. 17 -77777 Covance 6329-223 3M T-629:5.7 Cinical Pathology Blood and urine samples were collectedfrom each animal once before initiationof treatment(Day -27);on Days 37,62, 91, 153,and 182 of treatment;and on Days 245, 271,274,322, 364,456, and 546 duringrecovery(seeProtocolDeviations).Animals were fastedovernight,and urinewas collectedovernighton wet icebeforeblood sampling;water was providedad libitum.Blood was collectedfrom thefemoralveirl PotassiumEDTA was the anticoagulanutsed fbrhematology testsn;o antkoagalantwas used forthe chemistrytests.Blood samples were collectedfrom theanimal thatwas sacrificeadtan unscheduledinterval.Anftnalswere bledin sequentiaolrder on Days 37, 62,and 91 and inrandom orderatallotherscheduledcollectionst;hisisnot expectedto have an impact on theclinicaplathologyresults.The fbuowing were evaluated(see ProtocolDeviationsforexceptions). Hematology redblood cell(erythrocytec)ount differentiballood cellcount hemoglobin hematocrit mean corpuscularvolume mean corpuscularhemoglobin mean corpuscularhemoglobin concentration segmented neutrophilcount lymphocyte count monocyte count eosinophflcount basophilcount blood cellmorphology platelectount whiteblood cell(leukocytec)ount reticulocytceount glucose urea nitrogen creatinine totalprotein albumin globulin totalbilirubin cholesterol triglycerides alanineanjinotransferase aw.ahne phosphatase aspartateaminotransferase gamma glutamyltransferase ClWcal Chemistry sorbitodlehydrogenase creatineIdnase calcium inorganicphosphorus sodium potassium chloride bileacids amylase lipase* pancreatic-specifaimcylase highdensitylipoprotei(nHDL) (effectivweithcollectioonn Day 153) 18 Covance 6329-223 3M T-6295.7 Urinalyds volume (approximatel1y6 hours) specifigcravity pH protein bilirubin blood urobilinogen microscopicexaminationof sediment glucose ketones appearance Blood Hormone Determination Blood samples'(approximate5lymL) were collectefdrom each animalthreetimesbefbre initiatioofntreatmen(tDays-50,-40,and -27);on Days 37,62,91,and 182oftreatmnt; andon Days 217,245,274,32Z 364,458,and549 duringrecovery.Animalswere fastedovernightBlood was collectefdrom a femoralveinwithoutusingan anticoagulantS.ampleswere allowedtoclotand centrifugewdithinI hourafter collectiosne;rum was harvested.The serum was dividedintotwo approximateleyqual aliquotasnd storedina freezers,ettomaintain-60to-80*C,untilpacked on dryiceand shippedtoAni LyticsInc.foranalysiosfcortisotlestosteronees,tradioelstmne,estiiol thyroidstimulatinhgormone,totatlriiodothyronianned,totatlhyroxin.Beginningwith thecollectioonn Day 322 thesampleswere alsoanalyzedforfreetfflodothyronianned freethyroxin. Serum PFOS LevelDetermination Blood samples(approximatel2ymL) werecollectefdromeachanffiwoncebefore initiatioofntreatmen(tDay-27);duringWeeks I (Day 7),2,4,6,8,12,16,20,24, and 26,and 27 (Day 183)oftreatmenta;nd duringWeeks 27 (Days184,185,and 187), 28 (Day 190),29 (Day 198),30 (Day204),31 (Day211),35,39,43,47,51,53,57,61, 65,69,73,77,and79 (seeProtocoDleviations)A.nimalswere fasteodvernighatnd waterwas providedad aitum. Bloodwas collectefdrom a femoml veinwithoutusing ananticoagulantS.ampleswerecenwkged withinIhouraftercollectioandserum was harvested.Serum sampleswere storedina freezers,ettomaintain-60to-80*C,until packed on dryiceand shippedtotheSponsorforanalysisR.esultswillreported separately. 19 Covance 6329-223 3M T-6295.7 Additional Serum Collection At the scheduled terminal ne=psy and the necropsy of Animal No. 105506 (Group 4 male),blood samples(approximately20 mL) were collectedfrom thevena cava atthe time of exsanguhiation.Samples were collectedwithoutusingan anticoaplantaM centrifugedwithinI hour ofcollection.Serum was harvestedand storedina fi-eezesre,t tomaintain-60 to -80*C,untilpacked on dry iceand shippedtothe Sponsor fbrpossible futureanalysis. An aliquot(0.8mD of theadditionaslerum collectiosnamplescollectedfrom allanimals from Groups 1,Z 3,and 4 sacrificeadtthe terminalnecropsywere senton dry iceby the Sponsor to AniLyticsfortotaltriiodothyroninteo,talthyroxin,freetriiodothyroninaen,d freethyroxindeterminations. Urine and Feces PFOS Level Determination Urine [atleast2 mL (seeProtocolDeviations)]and feces(atleast5 g) were collected overnightorithe firsdtay of recovery(Day 184) and on Days 189,216, 275,321,and 366 duringrecovery.In additiona, 24-hour sample ofurineand feceswas collectedbefore the completionof 52 weeks of recovery.Except forthefirsdtay of recovery,animals were not fasted.Samples were storedina freezersettomaintain-10 to-30*C, untilthey were packed on dry iceand shippedto theSponsor. The samples willbe analyzedfor, PFOS. Resultswillbe reportedseparately. Additional Fecal Samples During.Week 23,a freshfecalsample (up to5 g)was collectedfrom allanimalsinthe controland high-dosegroups. Samples were collectedinwhite polypropylenecontainers afterpans were cleanedinthemorning to ensure thatthe fecalsamples were not more than6 hours old (seeProtocolDeviations).Samples were packed on dry iceand shipped tothe Mayo ClWc foranalysis. Interim Liver Biopsy Samples A sample of liver(approximatelyI to 2 g)was collectebdy biopsyfrom animalsin Group 4 onlyduringrecovery[Week 57 (Day 393),on thesame day as theserum PFOS blood collection]T.hissample was dividedintofourportionsas fbuows. 20 77 77777@ Covance 6329-223 3M T-6295.7 One subsample was preserved in 10% neutral-bufferedformdin, embedded inPandin, sectioned,stainedwith hematoxylin and eosin (duplicateslideswere prepmed), and exan-dnedmicroscopically. The second subsamplewas flash-frozeinnliquidnitrogenand storedina freezers,etto maintain-60to -800C, untilshippedtotheSponsorforanalysi(sseeProtocol Deviations)R.esultswillbe reportedseparately. The thirdsubsamplewas processedtoblockstageforelectronmicroscopicevaluation. The tissueblocksand a hematoxylinand eosin-stainesdlideforlightmicroscopywere transferretdoPAI. Tissueswillbe processedand evaluatedby electronmicroscopyby PAI. A reportwillbeprovidedby PAI forinclusioinnthefinalreport. The fburthsubsamplewas flash-frozeinnliquidnitrogenand storedina freezers,ettD maintain-60to -80"C,untilftmmferredtotheSponsorforpossiblefutureanalysis. Terminal Liver Biopsy Samples A sample of liver(approximatelyI g) was collectebdy biopsyfrom allanimalsin Group 3 duringrecovery[Week 80 (Day 554),one week aftertheserum PPOS blood collectio(nseeProtocolDeviations)]T.hissamplewas flash-frozienliquidnitrogen and storedina freezers,ettomaintain-60 to -800C,untilshippedtotheSponsorfor analysisR.esultswillbe reportedseparately. Anatomic Pathology-Terminal Sacrifice Necropsy. A necropsywas done on Animal No. 105509(Group 4 male)thatdiedon Day 155 (Week 23) and Animal No. 105506 (Group4 nmle)thatwas sacrificeidna moribundconditionon Day 179 (Week 26).DuringWeek 27 (Days 184 and 185)four animals/sex/grou(pGroups1through3)and fburfemalesand two males(Group 4).were fastedovernighta,nesthetizewdithketaniineand xylazinew,eighed,bledforrequired testse,xsanguinated,and necropsied.Animals were necropsiedinrandom order. Ile necropsyincludeda macroscopicexaminationoftheexternalsurfaceof thebody; all orificest;hecraniaclavity;theexternalsurfaceof thebrain;thenasalcavityand paramsal sinuses;cervicaltissueasnd organs;and thethoracica,bdominal,and pelvic cavitieasnd viscera. 21 Comee 6329-223 3M T-6295.7 Organ Weights. At scheduled and unscheduled sacrificest,he fbuowing organs (when present)were weighed; pairedorgans were weighed separately. adrenal(2) brain epididymis(2) kidney(2) liver ovary(2) pancreas testi(s2) thyroid(2)withparathyroid Organ-to-bodyweight percentagesand organ-to-braiwneight ratioswere calculated. Paimitoyl CoA Oiddase Determination& Representativesamples oftherightlateral lobeof liverwere collectedfrom each anl-nalatthescheduledsacrificew,eighed, flash-frozeinnliquidnitrogen,and storedina freezers,ettomaintain-60 to-800C,until analyzedforpahnitoylCoA oxidaseactivity. CeD ProliferatioEnvaluation. Representativseamples of theleftlaterallobeoflhe liver,leftana righttestesa,nd pancreaswere collectedand preservedinzincfonnalin.A second setoftissues(representativseamples of theleftlateralobeof theByer,leftand righttestesa,nd pancreas)preservedinformahn withoutzincwere alsoprepared.After fixations,amples were embedded inpamffin and shippedto PathologyAssociates Internation(aPlAI) forproliferaticoenllnuclearantigen(PCNA) evaluationi,ncluding the exaniinatioonf slidesstainedwith hematoxylinand eosin(seeProtocolDeviations). Resultswere providedby PAI forinclusioinnthefinalreport(Appendix7). Liver PFOS Determination. A sectionof liver(ipproximatel2y0 g) was collectefdrom each animalatthescheduledsacrificew,eighed,flash-frozeinnliquidnitrogen,and storedina freezer,settomaintain-60 to -80'C,untilshippedwith plasrm samples tothe Sponsor. Resultswillbe reportedseparately. Gallbladder and BileCollection.At the scheduledterminalsacrificfeoreach anin-W, bilewas collectedfrom thegallbladderm,easured,transferreidntoa cryovialand flash-frozeinnliquidn.itrogen.The gallbladdero,nce emptied,was weighed,and a section(approximately4 to 5 nun) from the mid-portionwas collected.The remaining gallbladdewras placedina cryovialand flash-frozeinnliquidnitrogen.The bileand gallbladdersamples were storedon dzy iceuntilmmfeffed to a freezersettomaintain 22 Covance 6329-223 3M T-6295.7 -60 to -800C. Samples were packed on dry iceand shippedtothe Sponsor forpossible futureanalysis. Tissue Preservadon. The followingtissues(when present)or representativseamples were collectedand preservedin10% neutral-bufferefdornudin,unlessotherwise specifie(dseeProtocolDeviations). adrenal(2) aorta brain cecum cervix colon duodenum epididymis(2) esophagus eyes [(2)preservedinDavidson's fixativfeorallsacrificeadnimals] femur withbone marrow (articular surfaceof the distalend) gallbladder heart ileum jejunum kidney(2) lesions liver lung mammary gland mesentericlymph node ovary(2) pancreas pituitary prosude rectum salivargyland [mandibular(2)] sciaticnerve seminalvesicle(2) skeletamluscle (thigh) skin spinalcord (cervicalt,horacica,nd lumbar) spleen sternum with bone marrow stomach testi[s(2)preservedinBouin's solutionforallsacrificeadnimals] thymus thyroid(2)withparathyroid trachea urinarybladder uterus vagina Histopathology. Tissues(asappropriatew)ere embedded inparaffins,ectioneds,tained withhematoxyhn and eosin,and examined microscopicallyfrom each animal inthe controland high-dosegroups (seeProtocolDeviationsforexceptions).In additionl,iver and thymus forallaninmls inthelow- and mid-dose groups and spinalcord gray matter from females inthe low- and rnid-dosegroups were embedded inparaffin,sectioned, stainedwithhematoxylin and eosin,and exan-Anedmicroscopically.Other tissuesa,s appropriatew,illbe retainedforpossiblefutureexamination. 23 Covance 6329-223 3M T-6295.7 Bone marrow smears from the sternum of each animal atscheduledand unscheduled sacrificewsere prepared,stainedwithWright'sstain,and retainedfbrpossible examination. Electron Mcroscopy. A sample of the liverwas collectedfrom each animal atthe scheduledterminalsacrificeT.issueswere processedintoblocksand,along with a heniatoxylinand eosin-stainesdlide,were shippedto PAI foranalysis.Resuks willbe providedforinclusionin the finalreporl Anatondc Pathology - Recovery Sacrifice Termination. Remaining animalsinGroup I were donatedon Day 549 and remaining animalsinGroup 3 were U=ferred toCovance 6329-268 on Day 560. On Day 549, remaining animals inGroup 4 were fastedovernight,anesthetizedwithketanime and xylazine,weighed, exsanguinated,and necropsied. The necropgy of theanimalsinGroup 4 includeda macroscopicexaminationof the externalsurfaceof thebody; allorificest;hecranialcavity;the externalsurfaceofthe brain;the nasalcavityand pamnasal sinuses;cervicaltissuesand organs;and the thoracica,bdoniinaland pelviccavitieasnd viscera. Liver Samples. Samples of liverwere collectedfrom animalsinGroup 4 as follows. One &wnple was preservedin 10% neutml-bufferedformalin,embedded inparaffin, sectioned,stainedwith hematoxylinand eosin(duplicateslideswere prepared),and examined microscopically. The second sample was flash-frozeinnliquidnitrogenand storedina freezers,etto maintain-60 to -80*C, untilshipped totheSponsor foranalysis.Resultswillbe reported separately. The thirdsample was processedtoblock stageforelectronmicroscopicevaluation.The tissueblocksand a hematoxylinand eosin-stainesdlideforlightmicroscopy were trmferred toPathologyAssociatesInternationa(lPAI).Tissueswillbe processedand evaluatedby electronmicroscopyby PAI. A reportwillbe providedby PAI fori.nclusion inthe finalreport. 24 Covenc6e329-223 3M T-6295.7 AdditionaTlissueand Senim Samples.Samplesoflung,kidneys,pleent,hyroid, bram abdominal fat,heart,(approxmiately3 g each),and bileand serum (eachas much as possible)were collected.These samples were flash-frozeinnliquidnitrogenand storedina freezer,settomaintain-60 to -80*C@ untilshippedtothe Sponsor forpossible futureanalysis. StatisticaAlnalyses Levene's test(Levene, 1960) was done to testforvariancehomogeneity. In thecase of heterogeneityof varianceatp :!0-.@05,==formations were used to stabiliztehe variance. Comparison teststook varianceheterogeneityintoconsideration. One-way analysisofvariance[ANOVA (Winer,1971a)]was used (ifapplicablet)o analyzeinitiablody weights,organ weights,pahnitoylCoA oxidaseactivitksc,ontinuous clinicaplathologyvalues,and blood hormone determinations.Ifthe ANOVA was significanDtu,nnett'st-tes(tDumett, 1964)was used fbrcontrolversustreatedgroup comparisons*. One-way analysisof covarianceCANCOVA (Winer, 1971b))was used toanalyzebody weights,with initiablody weightsasthe covariate.IftheANCOVA was significant, covariate-adjustemdeans were used forcontrolversustreatedgroup comparisons. Group comparisons(Groups 2 through4 versusGroup 1)were evaluatedatthe 5.0%, two-tailedprobabilitlyevel.Only datacollectedon or afterthe firsdtay of treatmentwere analyzedstatisticallSyt.atisticaanlalyseswere not performed on data collecteduringrecovery. Record Retention Allraw data,documentation,records,protocol,and specimens generatedas a resultof thisstudywiU be archivedinthestoragefacilitioefsCovance-Madison fora periodof 1 year. One yearafterthe submissionof thefinalreport,theSponsor willdeterzninethe finaldispositioonf thematerials.AU raw datastoredon magneticmedia and the protocol studycorrespondence,and an originalcopy ofthe finalreportwillbe retained ,byCovance-Madison. 25 Covanc6e329-223 3M T-6295.7 WithinI yearaftesrubmissioonfthefinarleporta,lloftheaforementionmeadterials from theSponsor'sdesignees(Ani LyticsInc.,3M F. T. & S,Mayo Clinic,and Pathology AssociatesInternationalw)illbe sentto theSponsor (Andrew Seacat,PhD, 3W by theSponsor's designees. RESULTS AND DLSCUSSION Observation of Animals ClinicalObservations. ClinicalobservationsaresununarizedinTables 1,2,and 3; individualdataarepresentedinAppendix 2. Individualaninud fatedatam-c also presentedinAppendix 2. Animal Nos. 105506 and 105509 given0.75 mg&gfday (Group 4 males)did not survive tothe scheduledterminalsacrificeA.ll otheraninalssurvivedtothe scheduledstudy termination.No clinicaolbservationsnotedintheanimalsthatsurvivedtothetmmihw sacrificoer iecoverywere attributablteothe n of PFOS. Animal No. 105509 (Group 4 male)diedafterdosingon Day 155 (Week 23). On Day 154 (Week 22) observationsofconstrictepdupilinboth eyes and paleguim were noted. Observationsnoted on Day 155 priorto dosingincludedfew,mucoid, liquida,nd black-coloredfecesand low food consumptiorl Approximately15 minutesafterdosing, theanimal was observed ashypoactivewithlaboredrespiratioannd palegums. This animal alsoappeared dehydratedand was coldtothetouch. These observationspersisted untilapproximately30 minutes postdosewhen theaninml was alsonoted asrecumbenl Shortlythereaftert,he animaldiedduringan examinationby a laboratoryanimal veterinariarAln enlargedliverwas detectedby palpation.The cause ofdeathwas determined tobe pulmonary necrosiswith severeacuteinflammation. On Day 179 (Week 26),Aninud No. 105506 (Group 4 inale)was sacrificeidna monbund condition.Low food consumptionwas notedon Day 178 (Week.26) and attheam observationintervaoln Day 179. Approximately5 to 10 minutespostdoseon Day 179, theanimal had excessivesalivationl,aboredrespirationa,nd hypoactiveand ataxic behavior.With the exceptionof excessivesalivationt,hesefindingscontinuedtobe observed approximately3 hours postdose. The cause ofthe moribund conditionwas not determined. 26 Covance 6329-223 3M T-6295.7 Two additionaalnimalshad noteworthyobservationsduringftvat=nt. One female in thegroup given thecontrolmaterialAnimal No. 105529, was examined by a laboratory animalveterinariaonn Day 5 (Week 1)due toobservationsof dehydration,thin appearance,clearoraland nasaldischarge,excessivesalivationa,nd audiblerespiration. Thisanimalwas diagnosedwithpneumonia and ftwed with LactatedRingees solution and antibioticsT.hisanimalhad recoveredby Day 14 (Week 2). AnimillNo. 105534 (Group 4 female)was diagnosedwith a tapeworzninfectionduringWeek 23 and was ftaed withpraziquantelNeitherinfectiownas testmaterial-related. Clinicalobservationdsuringrecoverywere typicaolf laboratorpyfi=es. Ophthahnology. Ophthalmic observationsaresummarized inTable4; individuadlata arepresentedinAppendix 2. There were no ophthalmicobservationsattheWeek 26 or Week 52 examinationsthat were testmaterial-relateAdn.imal No. 105529 (Group I fenule)was noted ashaving increasedmyelinationofthe rightopticnerve atthebaselineand Week 52 ophthahnic examinations,Because thisisa permanent, congenitalcondition,itwas noted atthe baselineand recoveryexaminationsonly and isnot relatedtotreatmentwithPFOS. Body Weights. Body weight dataareillustratiendFiguresI and 2 and summarized *in Tables 5 and 6;individualdataarepresentedinAppendix 3. Covariate-adjustemdean (CAM) body weightswere slightllyower innialesgiven 0.75mg/kgtday when compared withmales given thecontrolmaterialbeginningat Week 21;the differencewas significanattWeeks 23 and 27. In femalesgiven 0.75mg/kg/day,CAM body weightswere significantlyoweratWeeks II through16, 19 through23,and 25 through27 when compared with femalesgiventhe control material These decreaseswere likelytestmaterial-related. Differencesinbody weights were not apparentduringtherecoveryperiod. Food Consumption. Food consumption dataaresummarized inTables 1,2,and 3 (Summary of ClinicalObservations)i;ndividuadlataareincludedintheindividual clinicaolbservationsinAppendix 2. 27 Comce 6329-223 3M T-6295.7 Low food consumption was noted sporadicallfyoranimalsinthegroups giventhe controlmaterialand 0.03 mgtkgtday. The incidenceof low food consumption was generallyhigherinthegroups given 0.15 and 0.75 mglkgtday ascompared toanhnab giventhecontrolmaterialand appearedto be testmaterial-relateDdu.ring rmvery, instancesof low food consumption were sporadicand were shnilu foranimalsinthe controland treatedgroups. cuwcai Pathology Hematology, clinicaclhemistry,and urinalysidsataaresummarized inTables7 through45; individualdataarepresentedinAppendix 4. AdministrationofPFOS was associatedwith moderatelytomarkedly lower total cholesteroflorm,@lesand femalesgiven 0.75 mg/kgtday and high densitylipoprotein cholesteroflormales and femalesgiven 0.15 or 0.75mglkgtday. During the treatment period,theeffecton totalcholesteroblecame progressivelwyorse overfim. The effect on cholesterbwlas reversedwithin5 weeks of theend of trmtxnent,and theeffecton high densitylipopicteicnholesterowlas reversedwithin9 weeks of theend of treatment.Of uncertainrelationshitpo administratioonfPFOS was lower totalbifimbinconcentration forn-Aalegsiven 0.75 mglkgtday and higherserum bileacidconcentrationformales given 0.75 mgtkgtday. These potentiaelffectsof thetestniaterw were very mild,and neither was consideredadverse. PalmitoylCoA 03ddase Determination PahnitoylCoA oxidasedeterminationsaresummarized inTable 46; individualdataare presentedinAppendix 5. ResultsofpalmitoylCoA oxidasedeterminationswere not consideredtobe relatedtothe testmaterial Blood Horinone Determination Sumniary and IndividualBlood Hormone Data arepresentedinAppendix 6. 28 Covanc6e329-223 3M T-6295.7 EstmdivoalluewseregeneralolwyeornDays62,91,and182inmalegsiven 0.75mg/kgtday,althoughbecauseofthevariatioinnthedataonlytheDay 182valuewas significanEts.tronevalueswere generallhyigherinallofthetwed femaleson Days 37,62,and 91,althoughbecauseofthevariatioinnthedatanone ofthesevalues were significantdliyfferenatn,d thisdifferencweas notapparenton Day 182. Triiodothyroninvealueswerenotablyloweron Days 91 and 182inbothnmlesand femalesgiven0.15 or0.75nig/kgtdayW.ith thesinglexceptionon Day 91 ofmales given0.15mg/kgtday,allvalueswere significantlloywer.Therewere severaolther instanceisnwhich thehormone valuesintreatedgroupsdifferefdrom thoseofcontrols@ butthesedifferencewserenotconsistenotver6= orbetweensexes,were notclearly dose-relateadn,ddidnotappeartobe relatetdotheadministratioofnthetestmaterial Duringrecoverywere occasionailnstanceisnwhich thehormone valuesinftaed groups differesdlightlfyrom thoseof controlsb,utthosedifferencewsere notconsistenotver timeorbetweensexes,were notclearldyose-relateadn,d didnot appeartobe clearly relatetdotheadministratiofnthetestmaterial Apparentdifferenceisnthesexualmaturityofbothmalesand femalesusedinthisstudy complicatestheinterpretatioofnthehormone data. Anatomic Pathology Terminalbody weights,absoluteorganweights,organ-to-bodwyeightpercentagesa,nd organ-to-brawienightratioasresununarizedinTable47;incidenceosf macroscopicand microscopicobservationasresummarized inTables48 through51. Individuadlataare presentedinAppendix 5. Two offourmalesreceivin0g.75mg/kgtday(highdose)didnotsurvivteothescheduled terminalsacrifiacteWeek 27. At theterminaslacrificfee,malesinthegroupreceiving 0.75mgtkgtdayhad increaseadbsoluteliverweight,liver-to-bowdeyightpercentages, and liver-to-brwaeiinghtratiosI.nrmles,liver-to-bowdeyightpercentagewsere mcreasedinthehigh-dosegroup compared tothecontroglroup. Absoluteandrelative livewreightincreasewsere regardedastestniaterial-relaAtmeodn.g thena=scopic observationosn,ly"mottled"livewras consideretdestmaterial-relat'eMdo.ttled7l'ivers were observedinthetwo high-dosemalesand inone high-dosefemale.Of thetwo nmlesnotsurvivinugntilthescheduledterminalsacrificoen,e had "mottled"a'nd "large" liver. 29 Comee 6329-223 3M T-6295.7 Nficroscopicexamination of animals samificed atWeek 27 and of the two nales sacrificedatan unscheduled intervalyielded testmaterial-releed observations in the Byer. Inthreeof fourhigh-dosemales therewas hepatocchularhypertrophy,occuning eithercentrilobuuaroyr withoutregardtolocationwithinhepaticlobule& Hypertrophy, as describedinthemales,was observed inallhigh-dosefemales.The microscopic observationsof hepatocellulahrypertrophywere reflecteidnhigherliverweights inthe high-dosefemales.Hypertrophy was regarded as testmaterial-dependenitnhigh-dose animal . Centrilobulaorr diffusehepatocerularvacuolationwas alsotestmatmial-dependentin high-doseanimals,occurringintwo of fourfemalesand two offourmales. Multffocal hepaticvacuoleswere not regardedas testmaterw-dependent because theywere found in one of fourlow-dose males,and ina controland a low-dose feznale. Nficroscopicexan-dnatioonf livertaken atbiopsyon Week 57 from the high-doseanirnal didnot have any testimterid-relatedfindings. At therecoverysacrificeo,ne of two males and one oftwo femalesdid not have macroscopicobservations.The observationsintheotheranimalswere of adhesionson thelungsor liverand nodules inthethoraciccavity.None oftheseobservationswas consideredtestmaterw-related.Only liverswere examined microscopicallya,nd no test material-relatoebdservationswere made. The hepaticvacuolationobserved interminal sacrificaend unscheduleddeathanimals was not present,indicatintghatthehepatictest material-relatedffectswere reversible. CONCLUSION Treatment withPFOS by oralcapsuleforatleast26 weeks isgenerallyweu-tolerated*m male and femalecynomolgus monkeys atdoses up to 0.15mg/kgtday. Clinicaland pathologicalfindingsconsideredtobe associatedwith thetreatmentofPFOS afterat least26 weeks oftreatmentwere found tobe reversibldeuring a 52-week recovery period.Based on thedatapresentedinthisreport,theno-observable-adverse-effelcetvel is0.15 mg/kg/day. Dose analyses(providedby the Sponsor)and electronmicroscopy result(sprovidedby PAI) areforthcoming. 30 SIGNATURES Covance 6329-223 3M T-6295.7 ElizabetAh. Disch,BA Date StudyCoordinator Covance LaboratorieIsnc. PeterJ.Thomford,PhD Date StudyDirector Covance LaboratorieIsnc. 31 Covance 6329-223 3M T-6295.7 REFERENCES Dunnett,C. W., "New Tables forMukiple Comparisons with a ControL" Biometrics29-482-491(1964). Levene,H. "Robust TesisforEqualityofVariances,"ContributionstoProbabilfty Statistic@se,ds.)I.OUdn etaL, Ch. 25,pp. 278-292, StanfordUniversityPress: Stanford, Californi(a1960). Winer, B. J.,"Design and AnalysisofSingle-FactorExperiments,"StatisticParlinciples inEnerimental Deiia Second Ed.,CIL 3,pp. 149-260,McGraw-HUI: New York, New York (1971a). Winer, B. J.,"Analysisof Covariance,"StatisticParlinciplesinEERgd=ntal Desi Second Ed.,Ch. 10,pp.752-812,McGraw-Hill: New York, New York (1971b). 32 IOPHTHALMOLOGY REPORT Covance 6329-223 3M T-6295.7 Ophthalmicexaminationswere donebeforeinitiatioofntreatmentandduringWeeks 26 and 52. Therewere no ophthalmicobsexvationasttheWeek 26 orWeek 52 examinationtshatweretestmaterial-relatAendi.mal No. 105529(GroupI female)was noted ashavingincreasedmyelinatioonf therightopticnerveatthebaselineand Week 52 ophthalmicexaminationsB.ecausethisisa permanent,congenitaclondition,.h was notedatthebaselineand recoveryexaminationsonlyand isnotrelatetdotreatment withPFOS. IIL-rweere no testimtmial-relatoebdservationastanyoftheexaminations. Stephen1.Bismff,DVM Date Diplomate,ACVO VeterinarOyphthalmologist 33 PATHOLOGY REPORT Covanc6e329-223 3M T-6295.7 SUND4ARY The purposeofthestudywas toassm theeffecotfthetesmtateriaPle,rfluorooctane SuffoniAccidPotassiuSmalt(PFOS),on criticeanlzymelevelhso,rmonesa,ndother selectebdiochemicaplarameterwshen administerdeadilbyycapsulteocynomoigus monkeys foratleast26 weeks. The testmaterialwas administeredatdose levelsof0.03, 0.15,and 0.75ing/kg/day.One male given 0.75 mg/kg/day died on Day 155 afterdose administratioannd one nude given 0.75 mg/kg/day was sacrificeodn Day 179 due to poor health. AdministrationofPFOS was associatedwith moderatelyto markedly lower total cholesteroflormales and femalesgiven 0.75'mglkgtdayand highdensitylipoprotein cholesteroflormales and femalesgiven 0.15 or 0.75mgtkg/day. During thetreatment period,theeffecton totalcholesteroblecame progressivelwyorse over fm. The effect on cholesterbwlas reversedwithin5 weeks of theend of bvatmnt, and theeffecton high densitylipoproteicnholesterowlas reversedwithin9 weeks oftheend of atatmnt. Of uncertainrelationshitpoadministratioonf PFOS was lower totalbilirubicnoncentration formales given 0.75mgtkg/day and higherserum bileacidconcentrationformales given 0.75mg/kg/day. These potentiaelffectsof thetestmaterialwere very mild,and neither was consideredadverse. Two of fourmaies receiving0.75 mgtkg/day did not survivetothescheduledterminal sacrificaetWeek 27. At theterminalsacrificef,emales inthegroup receiving 0.75 mg&g/day had increasedabsoluteliverweight,liver-to-bodwyeight percentages@ and liver-to-brawienight ratios.In nialesh,ver-to-bodyweight percentageswere increasedinthehigh-dosegroup compared to controls.These absoluteand relativEever weight increaseswere regardedastestmaterial-relatedA.mong the macroscopic observationso,nly "mottled"liverwas consideredtestmaterial-relate"dM.ottle&'livers were observedinthe two high-dosemales and in one high-dosefemale. Of thetwo males not survivinguntilthescheduledtern-dnaslacrificeo,ne had "mottled"and "large" liver. Microscopicexaminationof animals sacrificeadtWeek 27 and thetwo unscheduled sacrificmeales yieldedtestmaterial-relatoebdservationsintheliver.In threeof four high-dosemales therewas hepatocellulahrypertrophy,occurringeithercentrilobullaorry 34 Covance 6329-223 3M T-6295.7 without regardto locationwithinhepaticlobules.Hypertrophy, as describedin the males,was alsoobserved in fourof fourhigh-dose females. The microscopic observationsof hepatoceuularhypertrophywere reflectedinhigherliverweights inthe high-dose females. Hypertrophy was regarded as testmaterial-dependent-M high-dose animals. CentrilobuL,iorr diffusehepatoceuular vacuolationwas alsotestmaterial-dependentin high-doseanimals,occurringintwo of fburfemales and two of fourmales. Mukifocal hepaticvacuoles were not regarded as testmaterial-dependentbecause they were found in one of four low-dose males, and in a controland a low-dose female. Nficroscopicexamination of livertaken at biopsy on Week 57 from thehigh-doseanimal did not have any testmaterial-relatefdindings. For therecovery sacrificaet Week 79, only high-dose animal were necmpsied. One of two males and one of two females did not have macroscopic observations.The observationsin the otheranimals were of adhesionson the lungs or liverand nodules in the thoraciccavity.None of theseobservationswas considered testmaterW-relatecL Only liverswere examined microscopically.No testmaterial-relateodbservationswere made. The hepaticvacuolationobserved in terminalsacrificaend unscheduled death animals was not present,indicatingthatthe hepatictestmaterial-relateedffectswere reversible. MEETHODS Four groups of male and female cynonwlgus monkeys were administeredthe test materialdailyby capsuleata dose levelof 0 (controlgroup;receivedcapsulescontaining lactose)0,.03,0.15,or 0.75 mg/kg of body weight/day(mg/kg/day).There were six animaLs/sexinthe controlgroup and the groups given 0.,15or 0.75 mg/kgtday; two animals/sexin thesegroups were designatedas recovery animals to be observed for approximately 26 weeks.posttreatinent.The recovery period was laterextended an additional26 weeks. There were four anfinals/seixn the group given 0.03 mg/kg/day. One male given 0.75 mg/kg/day died on Day 155 followingdose administrationa,nd one male given 0.75 mgikg/day was sacrificedon Day 179 due to poor health. 35 Covanc6e329-223 3M T-6295.7, Bloodandurinweerecollectfeodrhematologyc,liniccahlemistrayn,durinalystiessts once beforeinitiatioonftreatment(Week -4),on Days 37, 62,91, 153,and 182.and on Days 217, 245,364, 456, and 546 (recoveryanimals).High densitylipoprotein cholesterowlas not measured attheclinicaplathology intervalbseforeDay 153. The terminalsacrificaend necropsy occurred-on.Days 1841185;macroscopic observationswere recorded,organ weightswere obtained,and tissueswere placed in fixativaes specifiedby theprotocol Samples of therightlateralobeof the liverfrom each animal were frozenforanalysisofpabmitoylCoA oxidaseactivityS.ectionsof liver from each animal were processedto-blockforelectronmicroscopy and shippedtothe Sponsor'sdesigneeforultrastructareavlaluation.Samples ofliverfrom each anin3a] were frozenand shippedto the Sponsor forPFOS determination.The gaUbIWers and bilefrom each animalwere collectedf,rozen,and shippedtothe Sponsor. Samples of pancreas,leftand righttestesa,nd theleftlaterallobeof the liverwere preservedforcell proliferatioenvaluationby the Sponsor'sdesigneeusingprolifemtioncellnuclear antigen.Light microscopicexaminationswere done on collectedtissuesfrom control animalsand wiimalsgiven0.75mglkg/day. In additionl,iverand thymus from all animalsgiven 0.03 or 0.15 mg/kgtday and spinalcord gray matterfrom fenudesgiven 0.03or 0.15 mg/kgtday were examined by lightmi=scopy. During Week 57, liverbiopsieswere performed on therecoveryanimsilthathad been given 0.75mglkg/day. The tissuewas dividedintofbursamples. Three ofthe samples were used forlightmicroscopicexamination,ultwtructuralexaminationby the Sponsoes designee,and PFOS analysisby theSponsor,respectivelyT.he fburthsample was frozenand shippedtothe Sponsor forpossibleanalysis.At theend of therecovery period(Week 79),thecontrolanimalswere retumed totheCovance stockcolony,the animalsthathad been given 0.15 rng/kg/daywere mmferred toa subsequentstudyfor theSponsor (Covance 6329-268)followingliverbiopsyforPFOS analysisby the Sponsor,and the animalsthathad been given 0.75 mgtkg/day were sacrificeadnd necropsied.At thisrecoverynecropsy,macroscopic observationswere recorded,and threesamples of Ever were collectedforlightmicroscopicexamination,ultrastructural examinationby the Sponsor'sdesignee,and PFOS analysisby the Sponsor,respectively- StatisticalsliygnificandtifferencecsitedintheResultsand Discussionarebased on comparisons between the controland treatedgroups. 36 77 RESULTS AND DISCUSSION Covance 6329-223 3M T-6295.7 Mortanty Two of four males receiving0.75 mgikgtday (high dose) of the testmaterialdid not surviveto thescheduledterminalsacrificaetWeek 27. One was found dead on Day 155. 7be otherwas sacrificeodn Day 179 due topoor health.The cause of deathin theanimal found dead was judged to be pulmonary necrosiswithsevereacutefifflanumtion. Mcroscopically,thepulmonary lesionappearedto be an acuteexacerbationof a chronic lesion.The causeofdeathinthe moribund aninml was not determined.Allother animals survivedto theirscheduled sacrifices. CHnical Pathology Week -4. Resultsof clinicapla-thology testsindicatedno obvious group or individual healthabnormalities.Severalanimals,however, had mildlyelevatedal-mffie aminotransferasaectivitieastWeek -4. These animalswere primarilyfemales and were dispersedamong allofthe groups. By Day 37, theiralanineaminomwfemse activities were no longerelevated.The =mient increaseinthisliverenzyme was considered likelydue tosubclinicailnfectionwith HepatitisA virus,a common infectioinn cynomolgus monkeys, and did not negativelyimpact evaluationof thetestmaterial. Days 37, 62, 91, 153,and 182. Although therewere severalstatisticalsliygnificanotr otherwisenotabledifferencefsorclinicaplathologytestresultsbetween the controland treatedanimals,most ofthe differencewsere inconsistenotver fim or similarto differencepsresentbeforeinitiationftreatment(i.e.W,eek -4).The onlydifferences consideredtorepresenteffectsof thetestmaterialwere lower totalcholesterolformales and femalesgiven 0.75 mg/kgtday and lower high densitylipoproteicnholesteroflor males and femalesgiven 0.15or 0.75 mg/kglday. The effecton totalcholestemlbecame progressivelwyorse overtime. At Day 182,the mean totalcholesterocloncentrationfsor thenmles and femalesgiven 0.75 mg/kgtday were approximately68% and 49% lower, respectivelyt,hanthoseforthe controlmales and females.The effecton high density lipoproteicnholesterolmeasured only atDays 153 and 182,was proportionatelgyreater thanthatfortotalcholesterolAt Day 182,the mean highdensitylipoproteicnholesterol concentrationfsorthenialesand femalesgiven 0.75mg/kglday were approximately79% and 62% lower,respectivelyt,hanthoseforthecontrolnmles and females. 37 Comce 6329-223 3M T-6295.7 Of uncertairnelationshtiopadministratioofnPFOS was lowertotablilimbiri concentratiofnormalesgiven0.75mgtkgtday(statisticlaolwleyron Days 91,153,and 182)and higherserum bileacidconcentratiofnormalesgiven0.75mg/kg/day (statistichailglhyeron Day 182 only).Thesepotentiaelffectosfthetestmateriawlere verymild,and neitherwas consideredadverse. Statisticaslilgynificadnitfferencefsorothertestresultwsere consideredincidentaalnd unrelatetdoadministratiofnthetestniatmialThesedifferencewsere inconsisteonvter -timeorwere similatrodifferenctehsatexistebdeforetheinitiatioofntreatmenl UnscheduledsacrificAenimal No. 105506,a malegiven0.75mg/kg/day,was sacrificed on Day 179.The most notablefindingsforthisanimalwerea moderateneutrophuic leukocytosimsi,ldlyincreasesderum bileacidandglobulinconcentrationasn,d moderatelytomarkedlydecreasedtotalcholesteroalnd highdensitylipoprotein cholesterol. Days 2179245,3649456,and 546 (Recovery animab). The effecton cholesterowlas reversedby Day 217,and theeffecton highdensityUpoproteincholesterowlas reversed by Day 245. There were no otherfindingcsonsideretdorepresenptersistenotrdelayed occurrenceof toxiceffects. Anatomic Pathology Organ Weights. At theterminalsacrific(eWeek 27)femalesinthegroupreceiving 0.75mg/kg/day(high-doseh)ad increaseadbsolutleiverweight,liver-to-bowdeyight percentagesa,nd liver-to-brwaeiinghtratiosT.hisincreasweas regardedastestmterialrelatedI.n femalestheabsolutepancreasweightswere higherinanimalsreceiving0.03 mgtkg/day(low-dosed)m inthosereceivin0gmg/kgtday(control)I.ncreased pancreaticweights were not regarded as testmaterial-related. In males, liver-to-bodyweight percentageswere increasedin the high-dose group corppared to controls.The increasewas regarded as testmaterial-relatedL.eft adrenalto-body weight percentageswere also increasedinhigh dose nialescompared to controls. The significanceof the increaseleftadrenalweight percentagewas not known. 'Organ weights were not taken atthe recovery sacrificaet Week 79. 38 Covance 6329@-223 3M T-6295.7 Macroscopic Observations. Twenty one of 30 animals atthe terminal sacrificehad at leastone macroscopicobservation.One of theobservationswas obesity;itwas not regardedaspathologic.Thus, 20 aninab had macroscopicobsexvations.Of allthe macroscopicobservationso,nly "mottled"liverwas consideredtestniaterial-related. "Mottled"liverwas observed inthetwo high-dosemales and inone high-dosefenale. The otherobservationsincludedadhesionsand dark orred fociinany of severalorgans. Among high-dosefemales,each had atleastone observationofa darkor red fi)=. In addition,adrenalcorticesof thetwo high-dosemales and two of fourhigh dose females were recordedas dark In one high-dosefemale (Animal No. 105540),the red focusin the lungcorrelatedmicroscopicallywith hemorrhage. There were no microscopic correlatefsorthe otherobservations.Hence, darkor red fociwere consideredtoo nonspecifictobe consideredtestniaterial-relateAd.ditionallyd,ark and red fociwere observed inanimalsinotherdose groups. Dark adrenalcorticesdid not have a microscopiccorrelatet;hey,too,were not consideredtestmateri&related. Of the two nmles not survivinguntilthescheduledterminalsacrificeo,ne didnot have any macroscopicobservations.The other(Animal No. 105509)had severalobservation& Of theseobservationst,hoseintheliverwere consideredtestmaterial-relateTdh.e liver observationswere "mottle4fa'nd "large,. For therecoverysacrificaetWeek 79, only highdose animalswere necropsied.One of2 males and one oftwo femalesdid not have macroscopic observations.The observations inthe otheranimalswere of adhesionson the lungsor liverand nodulesinthe thoracic cavity.None of theseobservationswas consideredtestmaterial-related. becroscopic Observations. At theterminalsacrificea,lltissuesfrom the controland high dose groups were examined. AU tissueswere examined on the two high-dosemales not survivinguntiltheterminalsacrificet;hemicroscopicdatawere grouped withthatof thetemiinalsacrificaenimals.Liver,thymus,and spinalcord were examined from animals inthe low and intermediatedose groups. In threeof fourhigh-dosemales there was hepatocerularhypertrophy,occurringeithercentdiobullaroyr withoutregardto locationwithinhepaticlobules.Hypertrophy,asdescribedinthe males,was observedin fburof fourhigh-dosefemales.The microscopicobservationsof hepatocellular bypertrophywere reflectedinhigherliverweightsinthe high-dosefemales. Hypertrophy was regardedas testznaterw-dependentinhigh dose animals. 39 -low Covance6329-223 3M T-6295.7 Centdlobularor diftse hepatocellulavracuolationwas alsotestmaterw-dependent in high-dosewiftnalso,ccurringintwo offourfemalesand two of fourmales. Mulffocal hepaticvacuoleswere not regardedastestniaterw-depencientMuldfocal hepatic vacuoleswere found inone of fourlow dose males,and ina controland a low-dose female. Two otherobservationswere suggestiveof possibletestmaterialeffectsupon examinationof only controland high-doseanimals.When tissueswere examined from the low and intermediatedose groups aswell testmaterial-dependencywas not supported.In females,thymic atrophywas more pronounced indosed aninulsthan in controls.However, thereisno cleardose-dependentpatternand thus,thymic atrophy cannot be consideredtestmaterial-dependent.Intraneuronapligment was observed inthe spinalcord gray matterof two of fourhigh dose,fourof fourmid-dose,threeof four low-dose and one of fourcontrolfemales. And thus,spinalcord pigment was considered unrelatedto thetestmaterial Nficroseopicexaminationof livertaken atbiopsyon Week 57 from the high-doseaninud didnot have any testmaterialrelatedfindings. At therecoverysacrificel,iverswere examined from high-doseanimals.No test niaterial-relaotbesdervationswere made. The hepaticvacuolationobservedinterminal sacrificaend unscheduled deathanimals was not present,indicatintghatthe hepatictest material-relatedffectswere reversible. Inthoseaninmlsfrom which alltissueswere examined, thewidth ofthe femoralgrowth plateswere assessedas a generalindicationofthematurityof theanimals. Based on this indicatorn,mles were lessmature than females. RobertL Hall,DVM, PhD Diplomate,ACVP (ClinicaPlathology) Robert A. Leedle,DVM, PhD Diplomate,ACVP Date Date 40 Camce 6329-223 3M T-6295.7 CONE%CENTS ON THE DATA Various models of calculators,computers, and conq)uter progmtns were used to analyze datainthisstudy.Because differenmtodels round offor auacate numbers differendy, valuesinsome tables(e.g.m,eans, standarddeviationso,r individualvalues)may differ. slightlfyrom thoseinothertablesf,rom individuallcyalculatedaM or from statistical analysisdata. Neither the integritynor the interprewon of the data was affectedby these differences. Some tabulardata were compiled using Excel(& Version 7.0 software. The unitsfor the dose levelson the data collectionsystem (PTS) summary tablesare mglkg(day.- The number of animals listedin the heading of the summary tablefbr clinical observations reflectsthe number of animals assiped to each group atthe sm of the study. 7be sumniary tablefor clinicalobservations indicatesthe number of animals forwhich a condition was observed without regard to the specificnature,severity,reversibilky, number of incidences/animaL or the length of time the condition persistedl Only observations other than normal are indicatedon the summary of clinical. observations table. 7he specificdetailsfor comments in the individualclinicalobservations tablesthatare indicated with a '@C" can be found at the end of each group for each sex. 7be day of initiatioonf treatmentis"Day 1,Week I." Body weight data are entered at the startof a study week (e.g.,a body weight recorded on Day I isconsidered a Week I body weight, a body weight recorded on Day 8 isconsidered a Week 2 body weight). Differences in the population size(N) on the summary tablesforclinicaland.anatomic pathology are explained on the individualdata tables. Results of clinicalpathology samples collectedfor animals sacrificedat an unscheduled intervalappear on the individualclinicalpathology tablesforthe next scheduled interval. 7bese resultsare not on the summary tablesand are not included in the statistical analyses. Statisticaalnalyses were not done when there were two or fewer values for a parameter. 41 Coynce 6329-223 3M T-6295.7 CONbfflM ON THE DATA (continued) Bile volume islocated on the individualanatomic pathology tableunder the heading of "absoluteorganweight(gmms)". The valuelistefdorbileisnota weightand is designatedwitha unitofmL Some clinicaolbservationsdiscussedinthereportwere documented on theRequest for VeterinaryServicesform and wUl be archivedwith theraw data,buttheydo not appear on the individualclinicaolbservationstables. 42 CODES9 ABBREVIATIONSP AND UNrrS Covance 6329-223 3M T-6295.7 General Codes and Abbreviations Codes forClinicalPathology Abbreviationsand UnitsforClinicaHlematology Abbreviationsand UnitsfbrClinicaClhemistry Abbreviationsand UnitsforClinicaUldnalysis Codes forAnatomic Pathology Note: The followinglistosfcodes,abbreviationsa.nd unitsareused by Covance. Some, but not necessarilaylL of thisinformationmay be needed forthisreporl 43 General Codes and Abbreviations Covance 6329-223 3M T-6295.7 WK N Me=; MEAN CAM SD; S.D.;STAND DEV; STANDARD DEV; sd NA p c UNSCHM DISPATCH 7BW VETEXAM AM OBS 30-90 OB Week Number of measurements Arithmeticmean Covamte-adjusted mean Standarddeviation in a group Group mean issignificantldyifferenftrom themean ofthecontrolgroup (Group 1)at p:s 0.05 No value;not applicablen;ot present Present Comment found atthe end of each group foreach sex Unscheduled Observationsvmferred from thein-life module of thedatacollectiosnystem tothe necropsy module forreferenceduring necropsy.Observationsareduplicatesof thelastin-lifoebservations. Terminal body weight Number Veterinaryexamination Observationsrecordedduring thedaffy, morning observationinterval Observationsrecordedduring the30 to 90 n-dnutepostdoseobservationinterval 44 NS QS/QNS NR FS sc SH H SL L si NF u DT/DOT DB Ti TE RE EE SE PC PD Pi PL PA co BB PLASMO NO AGG FR UTD NO COAG CodesforCHWcal Pathology Covanc6e32gL223 3M T-6295.7 GENERAL CODES No sample Quantitnyotsufficient No repeat(samplevolume not sufficienftorrepeatanalysis) Fibrinstrands Sample clotted Slightlyhemolyzed Hemolyzed Slightllyipeniic Lipemic Slightlyicteric Ictelic Animal not fasted Unscheduled/moribund bleed Animal died on test Died duringbleeding Technicianjudgment torepeattest Technicalerror(instrumenotr technicianerrorthatresultsin unacceptabledata,eg.,unacceptableinstrumentoutput sample spillede,ntryof invaliddata) Recordmg error(recordedmcorrectdata,e.g.w,rong number, speumg error,mcorrectdate) Entryerror(incorreckteyboard entry) Sampling error Plateletcslumped Plateletsdecreased Plateletisncreased Plateletlsarge Plateletsappear adequate Color interferewsith test Heinz bodiesobserved Plasmodium No aggregation FTactious Unable to determine No coagulation 45 Covance 6329-223 3M T-6295.7 Codes forClinicalPathology(Continued) RESULTS NOT INCLUDED IN STATISTICAL ANALYSES Hemolyzed clinicaclhemistryor coagulationsamples Samples from animals atunscheduledintervals Protbrombintimes(PI)greaterdm 50 seconds Activatedpartw thromboplastintimes(PTD greaterthan I10 seconds Bleed times(BLETPAE) greaterthan30 minutes CODES FOR BLOOD CELL MORPHOLOGY The fbllowingscalewas used tomeasure thedegreeof anisocytosi(sANISO), pofifflocyto(sPiOsIK),polychromasia(POLY), hypochromasia(HYPO), and toidc neutrophil(sTOXNEUT): Scale I 2 3 4 Degree -"gon-nalforthespecies Slight Moderate Marked Not applicable Presence Not present Rare Few Moderate Many A Pale B Straw C Yellow D Dark yphow URINE APPEARANCE Color E Amber F Brown G Red IH Green I Black P Blue/green Q Blue R Orange Clarity lear K Hazy L Cloudy Miscellaneous M Debris 0 Feces 46 Codes forCHWad Pathology (Continued) Covmce 6329-223 3M T-6295.7 URINE CHEMETF.Y MULTISTIX'O STRJIP Urine Glucose - Negative + 100 nig/dL ++ 250 mg/dL ... 500 mg/dL i 1,000n*dL i 2:2,000ing/dL Urine Ketone - Negative + 5 mg/dL ++ 15 mg/dL +++ 40 mg/dL iiii 80 mgtdl i ii 160 mg/dL UrineBlood - Negative + Small ++ Moderate .. Large UrineUrobffiwgen - 0.2;;i/"@ + Imgtdl ++ 2 mg/dL 4 mgtdl 8mgtdL (In approximatelyI EhrliThunit) Urine Bffirubin - Negativ@+ Small ++ Moderate .. Large URINE SEDE%IENT Cells,Crystalr4Casts,and Comments A Amorphous urates B Amorphous phosphates C Uricacid D Triplephosphates E Calcium oxalate F Calcium carbonate lb Granular casts H Hyaline casts I Cellularcasts J Waxy casts K Unknown crystal P Mucous threads Q Sperm R Fecalcontamination S Pinworm ova found T Pinworm larvaefound U Parasiteova found 0 I Not present 2 1-5 per field 3 6-10 per Held 4 11-20 per field >20 per field Bacteria 0 Not present I Few 2 Moderate 3 Many 47 Covanc6e329-223 3M T-6295.7 Abbreviationasnd UnitsforCHWcal Hematology Test Red bloodceUcount Hemoglobin Hematocrit Mean corpuscularvolume Mean corpuscularhemoglobin Mean corpuscularhemoglobin concentration Plateletcount Mean platelevtolume Reticulocytecount Absolutereticulocytceount Heinz body count Erythrocytesedimentationrate Prothrombin time Activatedpartiadlromboplastintime Thrombin time Activatedcoagulationtime Fibrinogen Fibrin/fibrinogednegradationproducts Plateletaggregation Collagen Adenosine diphosphate Alpha 2-antiplasmin Bleedingtime Methemoglobin Plasma hemoglobin Myeloid/erythroirdatio Estimatedmyeloid/erythroirdatio VAiiteblood cellcount Differentiabllood ceU.count Nucleated red blood cellcount Correctedwhite blood ceU count Segmented neutrophilcount Band neutrophilcount Lymphocyte count Monocyte count Eosinophilcount Basophilcount Anisocytosis Polychroniasia Poofflocytosis Abbreviatio(nUnits) RBC (E61UL orXIC@/gL) HGB (G/DL) HCT(%) MCV (FL) MCH (PG) MCHC (%) PLT (E3/UL orXI O/izL) NPV (FL) RETIC (%) RETIC (E3M or XI 03/,UL) HEINZ (%) ESR (NEWM) PT (SEC) PTT (SEC) TT (SEC) ACT (SEC) FBR (MO/DL) FDP (UG/ML) PAGG/COL (%) PAGG/ADP (%) ANTFPLAS (%) BI.E TEME (SEC) NL71HGB (%) PLA HGB (MG/DL) NVE RATIO EST M/E RATIO WBC (E3/UL orXIOI//,L) NRBC (/100WBC) COR WBC (E3/TJLor XI 0'/gL) N-SEG (E3/UL or XIO/gL) and % N-BAND (E3[UL orX103/AL) and % LYWH (E3/UL or X103/gL)and % MONO (E3/UL or X103/AL) and % EOSIN (E3/UL or X103/izL)and % BASO (E3/UL or X103/,4L)and % ANISO (-,1,2,3) POLY (-,1,2,3) POIK (-,1,2,3) 48 Covance 6329-223 3M T-6295.7 Abbreviationsand UnitsforClinicaHlematoloo (Continued) Test Hypochroniasia HoweU-Jolly bodies Basophilicstippling Toxic neutrophils Atypicallymphocytes Aqueous whiteblood ceH count (righetye) Aqueous whiteblood cellcount(lefetye) Abbreviation(Units) HYPO (-,l,Z3) HJBODY (-,l.Z3.4) BASTIP (-,I,Z3) TOXNEUT (-,l,Z3,4) ATYPLYM (-,1,2,3,4) R EYE (WBCFUL) L EYE (WBCITJL) 49 Covanc6e329-223 3M T-6295.7 Abbreviationasnd UnitsforCHWcal Chemistry Test Glucose Urea nitrogen Urea Cmadnine Totalprotein Albumin Globulin Albumin/globulinratio Totalbilirubin Dhva bilirubin Indirecbtfflmbin Cholesterol Triglycezide Urea nitrogen/aeafininreatio TotalUpids Phospholipids High-densityUpoproteincholesterol Low-densitylipoproteicnholesterol Uric acid Aspartateaminoft-dnsfemse Alanineaniinotrawferase Alkalinephosphatase Ganum glutamylbmmfemse Sorbitoldehydrogenase Lactatedehydrogenase Creatinekinase Amylase I.Ipase Paln-dtoyCloA oxidase Calcium Ionizedcalcium Inorganicphosphorus Sodium Potassium Chloride Magnesium Zinc Strontium Iron Abbreviatio(nUnits) GLU (MG)DL) UN (MG/DL) LTREA (MGIDL) CREAT (MG/DL) T PRO (G/DL) ALB (G/DL) GLOB (G/DL) A/G RAno T BIU (MG/DL) D BILI (MG/DL) I BILI (MG/DL) CHOL(MG/DL) TRIG (MG/DL) UN/CREAT (RANO) T L.IPIDS(MG/DL) P LIPH)S (MG/DL) HDL (MG/DL) LDL (MG/DL) UA (MG/DL) AST/SGOT (IUIL) ALT/SGPT (W/L) ALK PHOS (IU/L) GGT (IU/L) SDH (rU/L) LDH (rU/L) CK (IU/L) AMYLASE (IU/L) LI]PASE (IU/L) PCOAO (IU/G) CA (MG/DL) ION CA (MG/DL) IPHOS (MG/DL) NA (MMOIJL) K O@M40LIL) CL (MMOIJL) MG (MEQ/L orMG(DL) ZN (MG/L orPP" SR (MGAL or PPM) FE (UG/DL) 50 Covanc6e329-223 3M T-6295.7 Abbreviationasnd UnitsforCHWad Chemistry(Continued) Test Excessiron Totalironbindingcapacity Unbound ironbindingcapacity Percentironsaturation Plasma cholinestemse Red blood cellcholinesterase Brain chounesterase Caudate putamen Hippocampus FTontalcortex Cerebellum Bicarbonate Serum hemoglobin Serum bileacids Fecalbileacids Average fecalweight Fecalbileacids(calculation) Osmolality Eectrophoresis Albumin Alpha-l-globulin Alpha-2-globulin Beta globulin Gamma globulin High-densitylipoprotein Low-densitylipoprotein Very-low-densitlyipoprotein Insulin Adrenocorticotropihcormone Cordsol Glucagon Triiodothyronine 'fbyroxine Creatinekinaseisoenzymes BB um mm Abbreviatio(nUnits) EX FE (UG/DL) T]IBC(UG/DL) UIBC (UG/DL) FE %SAT (%) CHEP (MU/NL) CHER (A4U/UL) CHEB (MU/?AL) CAUD PUT (UMOIIG) HUPPOCAM (UMOLIG) F CORTEX (UMOIJG) CEREBELL (UMOIJG) BICARB (MMOLA,) SER HGB (MG/DL) SBA (UMOIJL orMG/DL) FBA (UG/ML) FCC WGT (G) FBA (MG/Day) OSMO (MOSNI/KG) E ALB (G/DL) E A-I (G/DL) E A-2 (G/DL) E BETA (G/DL) E GAMMA (G/DL) E-HDL E-LDL E-VLDL INSULIN (UU/ML) ACTH (PG/UL) CORTISOL (UG/ML) GLUCAGON (PG/NIL) T3 (NG/DL) T4 (UG/DL) CK-BB (U/L) CK-MB (U/L) CK-MM (U/L) 51 Covanc6e329-223 3M T-6295.7 Abbreviationasnd UnitsforCHWcal U6mdysis Test Urinevolume 8 hour urinevolume Specificgravity Urineosmobuty Quantitativeurinary/cerebrospinal fluidprotein Urine proteinexcretion Urine chemistryMultistlxestrip UrinepH Urine protein Urine glucose Urine ketones Urinebilirubin Urine blood Urine urobilinogen Urine reducing substances Nficroscopic-examinationf urinesediment Red blood cellsper high-powerfield VAAte blood cellsper high-power field Epitheliacleus per high-powerfield Bacteriaper high-powerfield Castsper low-power field Crystalsper low-power field Urine appearance Comments Abbreviatio(nUnits) U VOL (ML) 8 HR VOL (NIL) SP GR U OSMO (MOSWKG) QUAN PRO (MG/DL) PRO EXC (MG) u PH U PRO (MG/DL) U GLU U KET U BILI U BLOOD UROBILI U RE SUB RBC (PER BPF) WBC (PER BPF) EPITH (PER HPF) BACT (PER HPF) CASTS (PER LPF) CRYSTALS (PER LPFI PER LPF2) URINE APPI or URINE CONMNTS or APP2 MiscellaneousCodes and Abbreviationsfor CHWcal Pathology Fecal occultblood Not applicable Fecalparasitedetection Not applicable Hemolytic potential Not applicable 52 .,"Arm Code T u D m P/0 6 EX NOTTAKEN MISSING UNSUITABLE AUTOLYTIC EXCLUDE Covance 6329-223 3M T-6295.7 Codes for Anatomic Pathology DefiWdon AND4AL DEATH CODES Terminal sacrifice Recovery sacrifice Found dead Moribund Donated TransferredtoCovance 6329-268 MACROSCOPIC CODES Indicatesthatorgan weight isexcludedfrom calculations Organ weight not taken;explanationgiven innecropsynotes Organ missingor lost Organ technicalluynsuitableforweighing Organ autolyzedand could not be weighed Weight was taken,but was excludedfrom allcalculations MICROSCOPIC CODES Codes BmNIx- Prefacing NeopkWc IF"mdings Primary,benign neoplasm Primary,malignantneoplasm Metastaticneoplasm locallyinvasiveneoplasm Other neoplasm DistributionofFindings Focal Diffuse Multifocal 53 Covanc6e329-223 3M T-6295.7 Codes forAnatomicPathology(Continued) Code DefiWtion GradesforSeveritoyrAmonnt I Minimal - theleastamount ofchange thatcan-be observed with the lightmicroscope 2 Slight- lessthanaverage amount ofchange,but readilydiscernible as abnormal 3 Moderate - the averageamount of change thatisexpected fora lesion 4 Moderately severe(marked)- a marked amount ofchange with possiblelossof functionof theaffectedcellsor organs 5 Severe - a greatamount of change withprobablelossof functionof the affectedcellor organsand frequentlyinvolveslargeareasof the organ Other NflcroscopicCodes IL Total p Finding present Finding not present TISSUE ABBREVIATIONS Abbreviation LF RT IN GL STOMACK GL STOMACI-L NONGL SAL,IV GI.,NLANDEB IN, ANT MES/PANC AUDITORY SEB GL LACRIMAL GLAND, EX HEMATO NEOPLASIA LACRIMAL GL, INT CAVITY, ABDOM SALIV GL,PAROTID I.N,TRACHEOBRON THYRO]ID/PARA DeflWtion Left Right Lymph node Gland Glandularstomach Nonglandulu Mandibular salivargyland Anteriormesenteric/pancreatliycmph node Auditory sebaceousgland Exorbitallacrimalgland Hematopoietic neoplasia Internalacrimalgland Abdominal cavity Parotidsalivarygland Tracheobronchiallymph node Thyroid withparathyroid 54 Figurie Mean BodyWeightData(kg)-Males 25-WEEKCAPSULETO)OCITYSTUDY WITH-PERFLUOROOCTANESULFONIC ACID POTASSIUM SALT (PFOST-6295) IN CYNOMOLGUS MONKEYS 5- 4.8- 4.6- 4.44.2- 4 3.8- -- ---- 0 mg&go --D-0.03 m 0.15m --X- 0.75m 3.6. 3.4. 3.2- 3 2.8-0 6 10 Is 20 25 30 3r3 40 46 so 65 60 65 70 Week 55 Figure2 Mean Body Weight Data (kg)- Females 3.8- 2C:,.WEEKCAPSULE TO)ACITY STUDY WITH-PERFLUOROOCTANE SULFONIC ACID poTASSIUM SALT (PFOS*,T-6295I)N.CYNOMOLGUS MONKEYS 3.6- V-.V--- %I---- 3.4- 32. ----A ........ 3 0 2.8. 2.6- 2.40 5 io Is 20 25 30 35 40 45 so 55 so 65 70 Week 56 Table I sumary of Clinical ObBervatLons Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERNUOROOCTME ACID POTASSIUM SALT IPPOSIT-6295) IN CYNOMOLGUS ------------------------------------------------------------------------- ------------ SilLnW'C MONKEYS ------------- ------------ NUMBER OF ANIMALS AFFECTED DAYS 1-185 CATEGORY SEX: GROUP: DOSE: ------M-ALE ------- ------FEMALE ------ 1 23 4 1 2 3 4 0 0.03 0.15 0.75 0 0.03 0.15 0.75 KEYWORD QUALIFIER NLTUBER: 6 4 6 6 6 4 ---- 6 ---- 6---------------------- ------------------------------------------------------------------------ *** TOP OF LIST APPEARANCE APPEARS DEHYDRATED PJWMEWR 0 0 0 2 1 0 0 0 0 0 0 1 0 0 0 0 BEHAVIOR ATAXIC HYPOACTIVE 0 0 0 1 0 0 0 0 0 0 0 2 1 0 0 0 DISCHARGE NASAL CLEAR ORAL CLOUDY VOMITUS WHITE IN COLOR CONTAINING FOOD INTACT CAPSULE PARTIAL CAPSULE EXCESSIVE SALIVATION APPEARS To BE MMGTRUATIM 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 1 0 0 1 1 3 1 2 0 2 1 0 0 0 0 1 0 0 2 0 1 0 3 3 0 0 3 0 0 0 1 1 0 0 0 0 0 0 0 4 4 2 4 DISCHARGE UNKNOWN POUND IN PAN RED IN COLOR SOURCE 1 0 0 0 1 0 0 0 57 Table I Summary of clinical observations Treatment. 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPON:EC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOL(;US MONKEYS ------------- ---------------------------------------------------------------------------------------------------- NUMBER or ANIMALS AFFECTED , DAYS 1-iss CATEGORY SEX: GROUP: DOSE: ------M-ALE ------- ------F-EMALE ------ 1 2 3 4 1 2 3 4 0 0.03 0.15 0.7S 0 0.03 0.15 0.75 KEMRD QUALIFIER NUMBER: 6 4 6 6 6----4---- 6----6---- ------------------ --------------------------------------------------------------------------- EXCRETION DISCOLORED FECES BLACK IN COLOR RED IN COLOR YELLOW IN COLOR DISCOLOR= URINE GREEN IN COLOR RED IN COLOR FEW FI=S LIQUID FBCES MUCOID FECES NO FBCES NON-FORMED FECES SMALL FECES EYES CONSTRICTED ms PUPIL RESPIRATION LABORED SKIN a PELAGE ALOPECIA DORSAL DORSAL-THORACIC 0 0 0 1 0 0 0 0 0 0 0 0 1 0 0 3 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 1 0 0 0 0 a 0 0 0 2 0 2 3 5 1 1 0 1 2 0 0 2 0 0 0 2 1 0 0 2 0 0 0 2 0 1 1 1 3 2 1 12 1 0 2 0 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 58 Table I Summary of Clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PMWLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEY$ ---------------- ------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS AFFECTED DAYS 1-185 CATEGORY SEX: GROUP: DOSB- -------MALE ------- ------FEMALE ------ 1 2 3 4 0 0.03 0.15 0.75 1 2 3 4 0 0.03 0.15 0.75 KEYWORD QUALIFIER NUMBER: 6 4 6---- 6 ---- 6 ---- 4 ---- 6 ---- 6 ---- ------------------------------------------------------------- ------------------ SKIN & PELAGE ALOPECIA DORSAL-THORACIC-LEFT FEW HEAD-OUIRE HEAD-CRAURAL HEAD-MAXILLARY-LEFT HEAD-MAXILLARY-RIGHT LIMB-HIND-LEFT LIMBS-ALL LIMBS-FRONT LIMM-HIM TAIL BROKEN SKIN HAM-LEFT DIGIT(S)-FRONT-12" HEAD-CRANIAL HZhD-MmILLARY-LEFT HEAD-KAXILLARY-RIGHT MOUTH PERT-ORSITAL-LEFT PERI-ORRITAL-RIGHT TAIL TAIL-DISTAL COLD TO TOUCH BODY_EnTrRE 0 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 a 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 1 1 0 0 0 0 0 0 0 a 0 0 1 0 0 0 0 a 0 0 0 1 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 1 0 1 0 1 0 0 0 2 1 0 1 0 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 59 Table I Summry of clinical Observations Treatment 26-WM CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOWIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS AFFECTED DAYS 1-185 CATEGORY SEX: GROUP: DOSE: -------KALE ------- 1 2 3 4 0 0.03 O.lS 0.7S ------FEMALE ------ 1 2 3 4 0 0.03 0.15 0.75 KEYWORD QUALIFIER NLTHBER* 6 4 6 6 6 4 6 6 ---------------------------------------------------------------------------------------------------------------- SKIN & PELAGE PALE SKIN HEHD-ENTIRE Gums RED SKIN LIMB-FROUT-RIGHT SCAB(S) HEAD-KAXILLARY-LEFT LIMB-FRONT-LEFT LIMB-FRONT-RIGHT BRUISED SXIN PERI-ORBITAL-LEFT QUALITATIVE FOOD LOW END OF LIST CONSUMPTION 0 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 1 3 3 6 6 5 3 6 6 60 Table 2 Summary of Clinical observations Recovery idays 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPOWIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS -------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS AFFECTED DAYS 186-365 CATEGORY SEX: GROUP: DOSE: -------MALE ------- ------FEMALE ------ .1 2 3 4. 1 2 3 4 0 0.03 0.15 0.75 0 0.03 0.15 0.75 KEYWORD NUMBER: 2 0 2 2 2 0 2 2 ----Q-UA-L-I-FI-E-R----------------------------------------------------------------------------------------------------- *** TOP OF LIST DISCHARGE APPEARS TO BE MENSTRUATING 0 0 0 0 1 0 1 1 EXCRETION FEW FECES LIQUID FECES NON-FORMED FECES 0 0 1 0 0 0 0 0 1 0 0 0 0 0 1 0 0 0 0 1 SKIN & PELAGE ALOPECIA FEET TAIL BROKEN SKIN DIGIT(S)-FRONT-LEFT 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 0 0 0 QUALITATIVE FOOD CONSUMPTION LOW END OF LIST 1 0 2 1 2 0 2 2 61 Table 3 summary of Clinical.observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAM SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNO14OLGUS MONKEYS --------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS AFFECTED DAYS 368-558 CATEGORY SEX: GROUP: DOSEs -------MALE ------- ------FEMALE ------ 1 2 3 4 1 2 3 4 0 0.03 0.15 0.75 0 0.03 0.15 0.75 KEYWORD QUALIFIER NUMBER: 2 0 2 2 2 0 2 2 --------------------------------------------------------------------------------------------------------------- *** TOP OF LIST APPEARANCE SWOLLEN HEAD-MAXILLARY-RIGHT 0 0 1 0 0 0 0 0 DISCHARGE VOMITUS CONTAINING FOOD APPEARS TO BE MENSTRUATING 1 0 2 0 1 0 1 0 0 0 0 0 1 0 0 1 DISCHARGE UNKNOWN FOUND IN PAN RED IN COLOR SOURCE 0 a 0 0 0 0 1 1 EXCRETION FEW FECES LIQUID FECES NO FECES MON-FORMED FECES 0 0 1 0 0 0 2 0 0 0 0 0 1 0 0 1 0 0 1 0 0 0 2 0 1 0 1 1 1 0 0 1 SKIN & PELAGE ALOPECIA LIMB-HIND-RIGHT 0 0 0 0 1 0 0 0 62 Table 3 summary of clinical*observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLDGUS MONKEYS ----------------------------------------------------------------------I-------------- ------------------------- NUMBER OF ANIMALS AFFECTED DAYS 368-558 CATEGORY SEX: GROUP: DOSE: -------MALE ------- 1 2 3 4 0 0.03 0.15 0.75 ------FEMALE ------ 1 2 3 4 0 0.03 0.15 0.75 KEYWORD QUALIFIER NUMBERT 2 0 2 2 2 0 2 ---- 2 --------------------- --------------------------------------------- -------------------------------------- QUALITATIVE LOW NONE END OF FOOD LIST CONSUMPTION 1 0 2 1 2 0 2 2 0 0 0 0 0 0 2 0 63 Table 4 summary of ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS AFFECTED WEEK -4 CATEGORY SEX$ GROUP: DOSE: -------MALE ------- ------FEMALE ------ 1 2 3 4 .0 0.03 0.15 0.75 1 2 3 4 0 0.03 0.15 0.75 KEYWORD QUALIFIER NUMBER: 6 4 6 6 6 4 6 6 ------------------------------------------------------------------------------------------------------ *** TOP OF LIST *** NO VISIBLE LESIONS NO VISIBLE LESIONS EYE-LEFT EYES 0 0 0 0 1 0 0 0 6 4 6 6 5 4 6 6 MISCELLANEOUS OPHTHALMICS INCREASED KYELINATION OF OPTIC EYE-RIGHT END OF LIST NERVE 0 0 0 0 1 0 0 0 64 Table 4 summary of ophthalmic observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTME SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN cyNONOLGUS MONKEYS -------------------------------------------------------------------------------------- NUMBER OF ANIMALS AFFECTED WEEK 26 CATEGORY SEXZ GROUP: DOSE: -------MALE ------- ------FE14ALE ------ 1 2 3 a 1 2' 3 4 0 0.03 0.15 0.75 0 0.03 0.15 0.75 KEYWORD NUMBER: 6 4 6 ----Q-UA-L-I-FI-E-R--------------------------------------------- 5---- 6----4----6---- 6--------------------- *** TOP OF LIST *** NO VISIBLE LESIONS NO VISIBLE LESIONS EYES END OF LIST 6 4 6 5 6 4 6 6 65 Table 5 Summary of ophthalmiq Observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS AFFECTED WEEK 52 CATEGORY SEX: GROUP: DOSE: -------MALE ------- 1 2 3 4 0 0.03 0.15 0.75 ------FEMALE ------ 1 2 3 4 0 0.03 0.15 0.75 KEYWORD QUALIPIER NUMBER: 2 0 2 2 2 0 2 2 --------------------------------------------------------------------------------------------------------------------------- *** TOP OF LIST *** NO VISIBLE LESIONS NO VISIBLE LESIONS EYES EYE-LEFT 2 0 2 2 1 0 2 2 0 0 0 0 1 0 0 0 MISCELLANEOUS OPHTHALMICS INCREASED MYELINATION EYE-RIGHT END OF LIST OF OPTIC NERVE 0 0 0 0 1 0 0 0 66 Table 6 Summary of Body Weight Data (kg) Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS -------------------------------------- -------------------------------------------------------------- ------- -------------------P-EKALE--@ SEX: --------------------M-ALE -------- ------------ 1 2 13 4 GROUP: 1 2 3 4 0.15 0.75 0 0.03 MO0/.K1G5/DAY MG0/.K7G5/DAY DOSE- 0 0.03 MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY W-E-E-K---U-NI-T-S--.----M-G-/K-G-/-DA--Y -------------------------------------------------------------------------------------- -in -1 b 1 2 3 4 5 N MEAN S.D. N MEAN S.D. N MEAN S.D. N CAM MEAN S.D. N CAM MEAN S.D. N CAM MEAN S.D. N CAM MEAN S.D. 3.2 0.43 6 3.3 0.45 6 3.3 0.45 6 3.3 33 0:44 6. 3 .3 3 .3 0 41 6 33 3:3 0.38 6 33 3:3 0.39 4 3.4 0.73 4 3.4 0.65 4 3.4 0.70 4 3.2 3.4 0.64 4 3.3 3.4 0.68 4 3.4 3.5 0.64 4 3.4 3.5 0.64 6 3.0 6 3.1 0.34 6 3.1 0.35 6 3.3 3.1 0.34 6 3.3 3.2 0.32 6 3.4 3.2 0.34 6 3.4 3.2 0.34 6 3.3 0.59 6 3.4 0.55 6 3.4 0.55 6 3.2 3.4 0.62 6 3.3 3.4 0.59 6 3.4 3.5 0.58 6 3.4 3.5 0.60 6 2.8 0.33 6 2.8 0.29 6 2.8 0.29 6 2.9 2.8 0.26 6 2.9 2.8 0.38 6 3.0 2.9 0.34 6 2.9 2.0 O.3S 4 3.0 0.55 4 3.0 0.55 4 3.1 0.60 4 3.0 3.1 0.59 4 3.0 3.1 0.59 4 3.0 3.1 0.65 4 2.9 3.1 0.60 6 3.0 0.38 6 3.0 0.41 6 3.0 0.41 6 3.0 3.0 .0.43 6 2.9 3.0 0.43 6 2.9 3.0 0.43 6 2.9 3.0 0.44 6 2.9 0.54 6 2.9 0.52 6 2.9 0.52 6 2.9 2.9 0.49 6 2.9 2.9 0.49 6 2.9 2.9 0.52 6 2.8 2.8 0.55 a Day -7. b Day -1. 67 Table 6 summary of Body weight Data (kg) Treatment. 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS -------------------------------------------------------------------------------------------------------------- WEEK SEX: ------------------K-A-L-E --------------------------------------FE-M-ALE 2 -------------------- 3 4 GROUP: 1 2 3 4 0.75 1 0 0.03 0.15 0.75 DOSE: UNITS: 0 MG/KG/DAY 0.03 MG/KG/DAY 0.15 MG/XG/DAY MG/KG/DAY MG/KG/DAY MO/KG/DAY MG/KG/DAY MG/KG/DAY ----------------------------------------------------------------------------------------------------- 6 N CAM MEAN S.D. 7 N CAN MEAN S.D. 8 N CAM MEAN S.D. 9 N CAN MEAN S.D. 10 N CAM MEAN S.D. 11 N CAM MEAN S.D. 12 N CAN MEAN S.D. 6 3.3 33 0:41 6 3.3 3.3 0.42 6 3.3 3.3 0.39 6 34 3:4 0.43 6 3.4 3.4 0.43 6. 3.4 34 0.46 6 3.4 3.4 0.47 4 3.4 3.5 0.63 4 3.4 3.5 0.64 4 3.4 3.5 0.64 4 3.4 3.6 0.60 4 3.4 3.6 0.60 4 3.5 3.7 0.68 4 3.5 3..7 0 69 6 3.4 3.2 0.34 6 3.4 3.2 0.33 6 3.3 3.2 0.30 6 3.4 3.2 0.29 6 3.3 3.2 0.33 6 3.4 3.2 0.33 6 3.4 3.2 0.29 6 3.4 3.5 0.60 6 3.4 3.5 0.63 6 3.4 3.5 0.65 6 3.5 3.5 0.65 6 3.4 3.5 0.65 6 3.5 3.6 0.66 6 3.4 3.5 0.65 6 2.9 2.8 0.36 6 3.0 2.8 0.38 6 2.9 2.8 0.39 6 3.0 2.9 0.&0 6 3.0 2.9 0.36 6 3.0 2.9 0.35 6 3.1 3.0 0.37 4 3.0 3.1 0.57 4 3.0 3.1 0.61 4 3.0 3.1 0.61 4 3.0 3.2 0.66 4 3.0 3.1 0.62 4 3.0 3.1 0.60 4 3.0 3.2 o.s9 6 2.9 3.0 0.48 6 2.9 3.0 0.47 6 2.9 3.0 0.47 6 3.0 3.0 0.46 6 3.0 3.0 0.44 6 3.0 3.0 0.46 6 3.0 3.0 0.49 6 2.8 2.8 0.55 6 2.9 2.9 0.48 6 2.9 2.9 0.50 6 2.9 2.9 0.55 6 2.9 2.9 0.55 6 2.8* 2.8 0.51 6 2.9* 2.9 0.50 68 Table 6 Summary of Body Weight Data (kg) Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH-PERFLUOROOCTANE ACID POTASSIUM SALT (PFOSIT-6295) IN CYNOMOLGUS SULFONIC MONKEYS ---- -------------------------------------------------------------------------------------------------------- 7 SEX: GROUP: --------------------1-4ALE --------------------- -------------------F-EMALE 1 2 0.135 0.745 10 0.023 --------------------- 3 4 0.15 0.75 WEEK DOSE: UNITS. 0 MG/KG/DAY 0.03 MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY --------------------------------------------------------------------------------------------------------- 13 N CAN MEAN S.D. 14 N CAM MEAN S.D. 15 N CAN MEAN S.D. 16 N CAN MEAN S.D. 17 N CAM MEAN S.D. le N CAN MEAN S.D. 19 N CAM MEAN S.D. 6 3.5 3.5 0.46 6 3.5 3.5 0.44 6 3.5 3.5 0.46 6 34 3:4 0.48 6 3.5 3.5 0.49 6 3.5 3.5 0.50 6 3.6 3.6 0.50 4 3.6 3.7 0.65 4 3.5 3.7 0.57 4 3.6 3.7 0.61 4 3.6 3.8 0.60 4 3.7 3.8 0.56 4 3.6 3.7 0.56 4 3.7 3.8 0.59 6 3.4 3.3 0.27 6 3.4 3.2 0.31 6 3.4 3.3 0.30 6 3.4 3.3 0.27 6 3.4 3.3 0.26 6 3.4 3.3 0.23 6 3.5 3.3 0.19 6 3.5 3.6 0.66 6 3.4 3.5 0.67 6 3.4 3.5 0.68 6 3.3 3.4 0.71 6 3.4 3.5 0.75 6 3.4 3.5 0.69 6 3.4 3.5 0.73 6 3.1 3.0 0.36 6 3.0 2.9 0.37 6 3.0 2.9 0.38 6 3.0 2.9 0.34 6 3.1 3.0 0.37 6 3.1 2.9 0.30 6 3.1 3.0 0.34 4 3.1 3.2 0.62 4 3.1 3.2 0.62 4 3.1 3.2 0.63 4 3.1 3.2 0.63 4 3.1 3.2 0.70 4 3.1 3.2 0.68 4 3.1 3.3 0.66 6 3.0 3.1 0.47 6 3.0 3.1 0.48 6 3.1 3.1 0.49 6 3.0 3.1 0.45 6 3.1 3.1 0.45 6 3.0 3.1 0.48 6 3.1 3.1 0.50 6 2.8* 2.8 0.46 6 2.8* 2.6 0.44 6 2.8* 2.8 0.38 62.8* 2.8 0.38 6 2.9 2.9 0.44 6 2.9 2.9 0.45 6 '2.9* 2.9 0.39 69 Table 6 summary of Bc)dyweight Data (kg) Treatment. 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTME SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------------7------------- SEX: -------------------MA-L-E --------------------------------------FE-M-ALE 2 -------------------- 3 4 1 2 3 4 0.75 1 0 0.03 0.15 0.75 WEEK GROUP: DOSE: UNITS: 0 MGIKG/DAY 0.03 MG/KG/DAY 0.15 MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY ------------------------------------------------------------------------------------------------------- 20 N CAN MEAN S.D. 21 N CAM MEAN S.D. 22 N CAM MEAN S.D. 23 N CAN MEAN S.D. 24 N CAN MEAN S.D. 25 N CAN MEAN S.D. 26 N CAN MEAN S.D. 6 3.5 3.5 0.53 6 3.6 3.6 0.55 6 3.6 3.6 0.56 6 3.6 3.6 0.58 6 3.6 3.6 0.63 6 3.7 3.7 0.61 6 3.7 3.7 0.67 4 3.7 3.8 0.59 4 3.6 .3.8 0.64 4 3.7 3.8 0.56 4 3.7 3.8 0.55 4 3.7 3.9 0.60 4 3.8 3.9 0.55 4 3.9 3.9 0.55 6 3.5 3.3 0.22 6 3.4 3.2 0.26 6 3.5 3.3 0.25 6 3.5 3.3 0.25 6 3.5 3.3 0.26 6 3.6 3.4 0.20 6 3.5 3.3 0.20 6 3.3 3.4 0.73 6 3.2 3.3 0.72 6 3.3 3.4 0.62 6 3.2* 3.3 0.67 5 3.3 3.4 0.69 5 3.3 3.5 0.72 5 3.3 3.4 0.73 6 3.1 3.0 0.34 6 3.0 2.9 0.34 6 3.1 3.0 0.37 6 3.0 2.9 0.31 6 3.0 2.9 0.32 6 3.1 3.0 0.37 6 3.1 3.0 0.37 4 3.1 3.2 0.67 4 3.1 3.2 0.70 4 3.1 3.2 0.68 4 3.1 3.2 0.68 4 3.1 3.2 0.76 4 3.2 3.3 0.76 4 3.1 3.2 0.79 6 3.1 3.2 0.48 6 3.0 3.0 0.46 6 3.1 3.1 0.44 6 3.1 3.1 0.46 6 3.1 3.1 0.46 6 3.1 3.2 0.46 6 3.1 3.1 0.46 6 2.8* 2.8 0.38 6 2.8* 2.8 0.33 6 2.8* 2.8 0.31 6 2.8* 2.8 0.35 6 2.8 2.8 0.32 6 2.8* 2.8 0.31 6 2.8* 2.0 0.35 70 Table 6 Summary of Body Weight Data (kg) Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH-PERFLUOROOCTANE ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ------- -------------------------------------------------------------------------------------------------------- SEX: ---------------------14-ALE --------------------- --------------------FE-MALE 2 -------------------- 3 4 GROUP: 1 2 3 4 0.15 0.75 1 0 0.03 0.15 0.75 DOSE: 0 MG/KG/DAY 0.03 MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY W-E-E-K ---U-NI-T-S--------------------------------------------------- ---------------------------------------------- 27 N CAN MEAN S.D. 6 3.7 3.7 0.68 4 3.8 3.9 0.56 6 3.5 3.3 0.26 4 3.0* 3.2 0.83 6 3.1 3.0 0.35 4 3.1 3.2 0.72 6 3.0 3.1 0.51 6 2.8* 2.8 0.37 71 Table 7 Summary of Body Weight Data lkg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------- ------------------------------------------------------------------------------------------------------- SEX: ---------------KHLE --------------- --------------FEMALE --------- GROUP: 1 3 4 1 3 4 0 0.15 0.75 DOSE: 0 MG/KG/DAY 0.15 MG/KG/DAY 0.75 MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY W-E-E-K---U-NI-T-S-:---------------------------------------------------------------------------------------------------- 28 N MEAN S.D. 29 N MEAN S.D. 30 N MEAN S.D. 31 N MEAN S.D. 32 N MEAN S.D. 33 N MEAN S.D. 34 N MEAN S.D. 2 3.5 0.42 2 3.6 0.42 2 3.6 0.42 2 3.7 0.42 2 3.8 0.42 2 3.8 0.42 2 3.8 0.42 2 3.1 0.21 2 3.1 0.28 2 3.0 0.28 2 3.1 0.35 2 3.2 0.35 2 3.2 0.28 2 3.2 .0.21 2 3.1 0.57 2 3.3 0.64 2 3.3 0.57 2 3.5 0.71 2 3.6 0.85 2 3.7 0.78 2 3.8 0.99 2 2.7 0.35 2 2.7 0.42 2 2.7 0.35 2 2.7 0.42 2 2.8 0.35 2 2.8 0.42 2 2.8 0.35 2 3.3 0.71 2 3.4 0.71 2 3.3 0.71 2 3.4 0.78 2 3.5 0.78 2 3.5 0.78 2 3.4 0.95 2 2.6 0.14 2 2.7 0.14 2 2.7 0.14 2 2.8 0.21 2 2.9 0.35 2 3.0 0.28 2 3.0 0.28 72 Table 7 Summary of Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULFONTC ACID POTASSIUM SALT (PFOS:T-6295) IN CYNOMOLOGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- SEX: ---------------MALE ----------4----- -----1---------FEMA3LE ---------4----- GROUP-. 1 3 0.15 0.75 0 0.15 0.75 DOSE: WEEK UNITS: 0 MG/KG/DAY MG/KG/DAY MG/KG/DAY NO/KG/DAY MG/KG/DAY NO/KG/DAY ----------------------- ------------------------------------------------------------------------ ------------ 35 N MEAN S.D. 36 N MEAN S.D. 37 N MEAN S.D. 38 N HEM S.D. 39 N MEAN S.D. 40 N MEAN S.D. 41 N MEAN S.D. 2 3.8 0.35 2 3.8 0.42 2 3.9 0.42 2 3.9 0.42 2 3.9 0.35 2 3.9 0.35 2 4.0 0.42 2 3.1 0.28 2 3.3 0.21 2 3.2 0.28 23.2 0.21 2 3.1 0.28 2 3.1 0.28 2 3.3 0.21 2 3.7 0.99 2 3.9 1.06 2 3.9 1.06 2 3.8 0.99 2 3.7 0.99 2 3.7 1.06 2 3.8 0.99 2 2.8 0.35 2 2.8 0.35 2 2.9 0.42 2 2.8 0.35 2 2.7 0.42 2 2.6 0.42 2 2.8 0.42 2 3.5 0.92 2 3.6 0.92 2 3.6 0.78 2 3.5 0.85 2 3.5 0.85 2 3.4 0.85 2 3.6 0.85 2 3.0 0.21 2 3.1 0.35 2 3.1 0.35 2 3.0 0.42 2 2.9 0.35 2 3.0 0.21 2 3.1 0.35 73 Table 7 summary of Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOKOLGUS MONKEYS ------- ----------------------------------------------------------------------------------------------------- SEX: ---------------MALE --------------- --------------FEMALE ---------4----- GROUP: 1 3 a 0.75 1 3 0 0.15 0.75 WEEK DOSE: UNITS: 0 MG/XG/DAY 0.15 MG/XG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY ----------------- -------------------------------------------------------------------------------- ------------ 42 N MEAN S.D. 2 4.0 0.20 2 3.2 0.21 2 3.8 1.06 2 2.7 0.42 2 3.6 .0.70 2 2.9 0.35 43 N MEAN S.D. 2 4.0 0.28 2 3.2 0.21 2 3.8 0.99 .2 2.7 0.42 2 3.6 0.78 2 3.0 0.42 44 N MEAN S.D. 2 4.2 0.28 2 3.3 0.21 2 3.8 0.92 2 2.8 0.35 2 3.7 0.92 2 3.1 0.35 45 N. MEAN S.D. 2 4.3 0.21 2 3.3 0.28 2 3.8 0.92 2 2.9 0.42 2 3.7 0.79 2 3.1 0.35 46 N MEAN S.D. 2 44 0:21 2 3.3 0.28 2 4.0 0.92 2 2.8 0.42 2 3.6 0.85 2 3.1 0.42 47 N MEAN S.D. 2 4.2 0.14 2 3.2 0.28 2 3.8 0.85 2 2.7 0.42 2 3.6 0.92 2 3.1 0.49 48 N MEAN S.D. 2 4.2 0.18 2 3.2 0.25 2 3.9 0.78 2 2.6 0.35 2 3.6 0.94 2 3.1 0.49 74 Table 7 SUMMary of Body Weight Data (kg) Recovery 26-WEEK CAPSUDE TOXICITY STUDY WITH PERFLUOROOCTANE SULFMIC ACID POTASSIUM SALT (PFOSiT-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- SEX: ---------------NKLE --------------- --------------FEKALE -------------- GROUP: 1 DOSE: 0 3 0.15 4 0.75 1 3 4 0 0.15 0.75 WEEK UNITS: HO/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY ---------------------------------------------------------------------------------------------------------------- 49 N MEAN S.D. 50 N MEAN S.D. 51 N MEAN S.D. 52 N MEAN S.D. 53 N MEAN S.D. 54 N MEAN S.D. 55 N MEAN S.D. 2 4.3 0.21 2 4.3 0.21 2 4.3 0.21 2 4.4 0.21 2 4.4 0.21 2 4.4 0.28 2 4.5 0.28 2 3.3 0.21 2 3.2 0.28 2 3.3 0.21 2 3.3 0.21 2 3.2 0.28 2 3.3 0.21 2 3.3 0.21 2 4.1 0.78 2 4.0 0.71 2 4.1 0.64 2 4.1 0.57 2 4.1 0.49 2 4.2 0.49 2 4.1 0.42 2 2.8 0.35 2 2.7 0.35 2 2.7 0.42 2 2.7 0.28 2 2.6 0.28 2 2.6 0.28 2 2.7 0.35 2 3.7 0.92 2 3.6 0.92 2 3.7 0.92 2 3.7 0.92 2 3.6 0.99 2 3.6 0.92 2 3.5 0.99 2 3.2 0.35 2 3.1 0.35 2 3.1 0.35 2 3.1 0.42 2 3.1 0.49 2 3.1 0.49 2 3.1 0.64 75 Table 7 Summary of Body weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYROMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- SEX: -------------M-A-LE ---------------------7-------FEMLE -------------- GROUP: 1 3 4 1 3 4 DOSE: 0 0.15 0.75 0 0.15 0.75 WEEK UNITS: MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY ---------------------------------------------------------------------------------------------------------------- 56 N MEAN S.D, 2 4.4 0.35 2 3.3 0.14 2 4.1 0.35 2 2.7 0.35 2 3.6 0.92 2 3.1 0.57 57 N MEAN S.D. 2 4.4 0.35 2 3.3 0.21 2 4.0 0.28 2 2.6 0.35 2 3.6 0.92 2 3.0 0.57 58 N MEAN S.D. 2 4.4 0.35 2 3.3 0.14 2 4.1 0.35 2 2.7 0.28 2 3.6 0.78 2 3.0 0.57 59 N MEAN S.D. 2 4.4 0.42 2 3.3 0.14 2 4.1 0.42 2 2.7 0.35 2 3.5 0.71 2 3.0 0.57 60 N MEAN S.D. 2 4.6 0.49 2 3.4 0.14 2 4.3 0.42 2 2.9 0.35 2 3.6 0.85 2 3.2 0.49 61 N MEAN S.D. 2 4.6 0.49 2 3.4 0.14 2 4.3 0.42 2 2.7 0.28 2 3.6 0.78 2 3.2 0.49 62 N MEAN S.D. 2 4.5 0.49 2 3.5 0.21 2 4.4 0.49 2 2.7 0.42 2 3.6 0.78 2 3.2 0.57 76 Table 7 Summary of Body weight Data (ka) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- SEX: -------------MA-L-E --------------------------F-EM-ALE -------------- GROUP: 1 3 4 1 3 4 DOSE: 0 0.15 0.75 0 0.15 0.75 W-E-E-K--U-N-IT-S-:----MG-/-KG-/-D-AY----M-G-/K-G-/-DA-Y----M-G/-K-G-/D-A-Y----MG-/-K-G/-D-AY----M-G-/-KG-/-DA-Y----M-G-/K-G-/-DA-Y------------------------------------------- 63 N MEAN S.D. 64 N MEAN S.D. 6S N MEAN S.D. 66 N MEAN S.D. 67 N MEAN S.D. 68 N MEAN S.D. 69 N MEAN S.D. 2 4.5 0.57 2 4.4 0.64 2 4.4 0.57 2 4.4 0.64 2 4.5 0.57 2 4.6 0.57 2 4.7 0.57 2 3.4 0.14 2 3.4 0.14 2 3i4 0.07 2 3.3 0.14 2 3.4 0.14 2 3.5 0.21 2 3.5 0.14 2 4.4 0.42 2 4.5 0.21 2 4.4 0.21 2 4.3 0.28 2 4.4 0.21 2 4.5 0.21 2 4.5 0.28 2 2.9 0.35 2 2.7 0.35 2 2.7 0.35 2 2.6 0.28 2 2.7 0.35 2 2.7 0.35 2 2.7 0.28 2 3.6 0.71 2 3.6 0.78 2 3.S 0.78 2 3.5 0.78 2 3.6 0.71 2 3.6 0.78 2 3.6 0.85 2 3.2 0.57 2 3.2 0.64 2 3.1 0.57 2 3.1 0.57 2 3.2 0.57 2 3.2 0.64 2 3.2 0.71 77 Table 7 Summary of Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------ ------------------------------------------------------------------------------------------------------ SEX: GROUP: ---------------MALE --------------- --------------FEMALE 1 3 4 1 3 0.15 0.75 0 0.15 -------------4 0.75 WEEK DOSE: UNITS: 0 MG/KG/DAY MG/KG/DAy MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY --------------------------------------------------------- -------------------------------------- 70 N MEAN S.D. 71 N MEAN S.D. 72 N MEAN S.D. 73 N MEAN S.D. 74 N MEAN S.D. 75 N MEAN S.D. 76 N MEAN S.D. 2 4.6 0.57 2 4.7 0.64 2 4.8 0.111 2 4.7 0.71 2 4.8 0.85 2 4.8 0.78 2 4.8 0.85 2 3.5 0.07 2 3.5 0.07 2 3.6 0.07 2 3.5 0.07 2 36 0:07 2 36 0:07 2 3.6 0.07 2 4.5 0.21 2 4.4 0.28 2 4.5 0.21 2 4.4 0.21 2' 4.5 0.21 2 4.5 0.21 2 4.5 0.21 2 2.7 0.35 2 2.7 0.35 2 2.7 0.35 2 2.7 0.35 2 2.7 0.42 2 2.7 0.28 2 2.7 0.28 2 3.6 0.78 2 3.6 0.85 2 3.7 0.78 2 3.6 0.85 2 3.7 0.78 2 3.7 0.78 2 3.7 0.71 2 3.2 0.71 2 3.2 0.71 2 3.3 0.78 2 3.2 0.78 2 3.3 0.78 2 3.3 0.78 2 3.4 0.78 78 Table 7 Summary of Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAM SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOBGUS MO M YS ------------------------------------------------------------------------------------- ------------ SEX: --------------MA-LE ---------------------------F-E-MALE -------------- GROUP: 1 3 4 1 3 4 DOSE: 0 0.15 0.75 0 0.15 0.75 WEEK UNITS: MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY ---------------------------------------------------------------------------------------------------------------- 77 N MEAN S.D. 78 N MEAN S.D. 79 N MEAN S.D. so N MEAN S.D. 2 4.7 0.85 2 4.7 0.92 2 4.7 0.92 0 2 3.5 0.07 2 3.5 OiO7 2 3.5 0.00 2 3.3 0.21 2 4.4 0.14 2 4.4 0.14 2 4.4 0.07 0 2 2.7 0.35 2 2.6 0.28 2 2.7 0.35 0 2 3.7 0.78 2 3.5 0.85 2 3.6 0.85 2 3.4 0.85 2 3.3 0.78 2 3.2 0.85 2 3.3 0.85 0 79 Table 8 Summary of Clinical Hematology Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH iERFbUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID DOSE mg/kg/day ------ RBC X106/,uL -------- HGB G/DL -------- HCT % -------- mcv FL -------- MCH PG -------- MCHC .% -------- PLT X103/,UL -------- RETIC % X,04/0 -------- ---- 0 MEAN 6.45 12.2 41.2 63.9 19.0 29.0 530 .3 S.D. .275 .36 1.30 2.32 .87 .56 125.0 .19 N 6 6 6 6 6 6 6 6 0.03 MEAN 6.99 12.4 42.9 61.5 17.8 29.0 574 .4 S.D. N .688 4 .46 2.95 2.51 1.13 1.34 210.3 .24 4 4 4 4 4 4 4 0.15 MEAN 6.76 12.6 42.9 63.5 18.1 29.5 493 .5 S.D. N .315 6 .41 1.88 2.38 6 6 6 .76 .41 109.0 .53 6 6 6 6 0.75 MEAN 6.88 12.5 43.1 62.8 18.2 29.0 415 .5 S.D. .575 .82 2.06 3.44 1.01 .61 202.6 .47 N 6 6 6 6 6 6 80 Table 8 Summary of Clinical Hematology Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANLI SULFONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ WBIC X10 /,uL -------- N-SEG X103/)AL -------- LYIPH X10 /,wL -------- MONP XIO IML -------- EO@@IN XIO /,uL BASO X103/,UL -------- -------- N-SErit -------- LYMPH% -------- MONO% -------- ROSIN ------ 0 MEAN 8.6 3.9 4.0 .6 .1 .0 44 47 7 S.D. 1.76 1.28 .90 .24 .08 .05 8.9 9.2 2.4 N 6 6 6 6 6 6 6 6 6 0.03 MEAN 11.0 5.2 4.6 .8 .2 .0 47 43 8 S.D. 1.00 1.88 1.05 .48 .17 .00 15.2 9.4 4.4 N 4 4 4 4 4 4 4 4 4 0.15 MEAN 11.9 6.6 4.1 .9 .2 .0 54 36 8 S.D. 1.95 2.42 1.14 .25 .31 .04 13.4 10.9 3.3 N 6 6 6 .6 6 6 6 6 6 0.75 MEAN 9.4 3.7 4.3 1.1 .2 .1 39 46 12 S.D. 2.53 1.40 1.25 .53 .25 .08 10.9 9.5 3.3 N 6 6 6 6 6 6 6 6 6 81 Table 8 Summary of Clinical Hematology Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTAKE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID DOSE mg/kg/day ------ RPC XIO /,UL -------- HGB G/DL -------- HCT t -------- mcv FL -------- MCH PG -------- MCHC % -------- PIT X103 /,uL -------- RETIC t -------- RET xiol/.u ----- 0 MEAN 6.09 12.0 39.3 64.7 19.7 30.4 539 .6 S.D. .681 .97 3.93 4.51 1.81 .87 79.5 .46 N 6 6 6 6 6 6 6 6 0.03 MEAN 6.31 11.5 39.5 62.7 18.3 29.2 482 .4 S.D. .522 1.06 3.26 4.49 1.73 .71 72.4 .31 N 4 4 4 4 4 4 4 4 0.15 MEAN 6.54 12.0 40.1 61.4 18.3 29.8 del .4 S.D. .320 .49 1.97 2.79 .50 .68 100.9 .26 N 6 6 6 6 6 6 6 6 0.75 MEAN 6.50 12.1 41.5 63.9 18.7 29.2 435 .2 S.D. .195 .50 1.68 1.14 .50 .52 108.9 .18 N 6 6 6 6 6 6 6 6 82 Table 8 summary of Clinical Hematology Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFot4lC ACID MONKEYS DOSE mg/kg/day ------ X10W.P/C.uL -- ----- N-SEG X103/1,L -------- LYMPH X103/,uL -------- MONO X10'/,uL EOSIN X10'/,uL -------- -------- BASO x 10'/,UL -------- N-SEG% -------- LYMPH% -------- MONO% -------- EOSI ----- 0 MEAN 10.2 S.D. 2.52 N 6 4.6 1.14 6 4.5 1.36 6 .8 .3 .0 45 44 7 .24 .28 .05 8.3 7.6 1.2 6 6 6 6 6 6 0.03 MEAN 8.7 5.0 2.9 .6 .1 .0 55 35 8 S.D. 2.41 2.52 .79 .17 .05 .05 14.3 11.6 2.8 N 4 4 4 4 4 4 4 4 4 0.15 MEAN 10.1 5.1 3.8 .8 .3 .0 48 40 9 S.D. 2.94 2.81 .40 .20 .27 .04 13.0 8.4 3.9 N 6 6 6 6 6 6 6 6 6 0.75 MEAN 9.0 4.8 3.2 .8 .1 .0 54 35 9 S.D. 3.08 1.70 1.66 .32 .18 .04 10.7 9.7 4.2 N 6 6 6 6 6 6 6 6 6 83 Table 9 Summary of Clinical Hematology Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ RBC HGB HCT mcv MCH MCHC PLT RETIC RETZ XIO('/i4L G/DL t FL PG t X10'/,uL t xiol/,Ul -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN 6.45 12.4 40.6 63.0 19.1 30.4 486 .2 S.D. .221 .55 1.44 2.74 .97 .58 117.8 .16 N 6 6 6 6 6 6 6 6 0.03 MEAN 6.86 12.5 42.4 61.9 18.2 29.5 532 .4 S.D. .501 .38 3.93 4.61 1.17 1.69 146.1 .35 N 4 4 4 4 4 4 4 4 0.15 MEAN 6.66 12.5 41.2 62.0 10.8 30.3 476 .4 S.D. .385 .27 .76 2.96 1.06 .53 59.6 .14 N 6 6 6 6 6 6 6 6 0.75 MEAN 6.53 11.8 61.7 18.1 29.4 383 .4 S.D. .431 .57 1.74 2.63 .85 .57 164.3 .10 N 6 6 6 6 6 6 6 6 84 Table 9 Summary of CliniCal Hematology Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT.(PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID DOSE mg/kg/day ------ mw X10 /PL -------- N-SE(A Xio'liAL -------- LYMPH X10'/,uL -------- MONP X10 /.uL BO.@IN X10 /JAL -------- -- ----- BASO X10'/,WL N-SEG% LYMPH% MONO% zosi -------- -------- -------- -------- ----- 0 MEAN 7.6 3.9 3.1 .5 .0 .0 50 43 7 12.8 3.4 S.D. 1.98 2.01 .67 .31 .08 .08 14.4 6 6 6 6 6 6 N 6 6 6 0.03 MEAN 10.8 6.3 3.7 '.5 .2 .0 58 36 5 14.2 1.7 S.D. 1.89 2.40 1.26 .17 .05 4 .00 15.9 4 4 4 N 4 4 4 0.15 MEAN 10.0 62..203 3..291 ..264 ..232 ..005 5182.5 3130.4 63.6 6 6 6 6 S.D. 2.06 N 6 6 6 6 6 0.75 MEAN 10.3 6.6 2.9 .6 .1 .0 62 30 7 7.S 2.7 S.D. 4.16 3.69 .52 .18 .11 .05 6 6 6 9.8 6 6 6 N 6 6 6 85 Table 9 Summary of Clinical Hematology Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ RPC X10 /,uL -------- HGB G/DL -------- HCT t -------- mcv FL -------- MCH PG -------- MCHC -------- PIT X10'/,wL -------- RETIC t RET XiolIA4 -------- ----- MEAN 6.41 1 2.2 40.5 63.1 19.0 30.2 538 .3 S.D. .351 .69 2.42 2.31 .83 .29 84.2 .16 N 6 6 6 6 6 6 6 6 0.03 MEAN 6.60 11.8 40.6 61.8 18.1 29.2 417 .3 S.D. .664 .97 2.92 6.28 1.80 .48 23.6 .28 N 4 4 4 4 4 4 4 4 0.15 18.1 29.7 431 .3 MEAN S.D. 6.55 .343 11.8 .41 39.7 1.06 60.7 2.69 .75 .29 85.3 .12 N 6 6 6 6 6 6 6 6 0.75 MEAN 6.21 11.6 39.1 63.0 18.6 29.6 469 .3 S.D. .280 .38 1.96 1.48 .44 .69 95.4 .23 N 6 6 6 6 6 6 6 6 86 Table 9 Sumnary of Clinical Hematology Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ W, X10 liAL -------- N-SIEG X103 /j4L LYIPH X10 /,uL -------- -------- MONO X103 /,wL -------- EOSIN X103/tiL -------- BASO X103/.uL ---- --- N-SEG% LYMPH% MONO% EOS -------- -------- -------- ---- 0 MEAN 12.7 7.8 3.6 1.1 .3 .0 59 30 8 S.D. 4.75 3.77 1.59 .67 .26 .08 18.2 16.2 2.3 N 6 6 6 6 6 6 6 6 6 0.03 MEAN 9.6 5.7 2..882 ..284 ..217 ..005 6100.6 296.0 28.1 S.D. 2.37 1.90 N 4 4 4 4 4 4 4 4 4 0.15 MEAN 9.1 5.5 2.9 .5 .2 .0 56 - 35 6 S.D. 2.66 2.48 .72 .13 .19 .00 17.0 15.7 1.6 N 6 6 6 6 6 6 6 6 6 0.75 MEAN 8.9 5.3 2.9 .6 .1 .0 56 35 7 SN.D. 2.865 3.169 1.066 .26 0 .06 8 .600 156.1 136.7 26.7 87 Table 10 Summary of Clinical Hematology Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ RBC HGB HCT mcv -MCH XlD'/,UL G/DL t FL PG -------- -------- -------- -- ----- ------- MCHC PLT RETIC RET t X10'/IAL % xiol/," -------- -------- -------- ----- 0 MEAN 6.49 12.5 41.1 63.3 19.2 30.4 522 .3 S.D. .292 .53 1.78 3.03 .95 .84 126.9 .27 N 6 6 6 6 6 6 6 6 0.03 MEAN 6.84 12.4 41.4 60.7 18.2 29.9 536 .4 S.D. .437 .33 1.36 2.92 .91 .62 152.1 .45 N 4 4 4 4 4 4 4 4 0.15 MEAN 6.60 12.5 40.7 61.7 18.9 30.6 504 .3 S.D. .315 .52 1.42 2.56 .87 .50 97.3 .25 N 6 6 6 6 6 6 6 6 0.75 MEAN 6.73 12.3 41.2 61.3 19.3 29.8 437 .3 S.D. 516 .75 2.31 3.02 .72 .52 217.8 .19 N 6 6 6 6 6 6 6 6 88 Table 10 Summary of Clinical Hematology Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ PC W X10 /.uL -------- N-SEG XIO'/,UL -------- LYMPH X10'/,UL -------- MONP XIO /jiL EOSIN X10'/,ML -------- -------- BASO x 103 IAIL -------- N-SEG% -------- LYMPH% -------- MONO% -------- EOSI ----- 0 MEAN 7.3 3.0 3.5 .6 .1 .0 42 48 8 S.D. .81 .68 .87 .26 .08 .05 10.5 8.2 3.2 N 6 6 6 6 6 6 6 6 6 0.03 MEAN 10.5 6.1 * 3.4 .8 .2 .0 58 32 a S.D. 1.79 1.51 .82 .38 .05 .00 9.5 6.5 3.5 N 4 4 4 4 4 4 4 4 4 0.15 MEAN 11.8 7.0 * 3.9 .7 .2 .0 56 35 7 S.D. 3.02 3.16 1.18 .40 .13 .05 16.3 14.6 4.0 N 6 6 6 6 6 6 6 6 6 0.75 MEAN 9.6 5.3 3.4 .6 .2 .0 52 38 6 S.D. 2.97 2.52 .52 .23 .21 .09 10.0 11.2 1.0 N 6 6 6 6 6 6 6 6 6 89 Table 10 Summary of Clinical Hematology Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH @ERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYMOMOLGUS SULPONIC MONKEYS ACID DOSE mg/kg/day ------ RSC X10 I/-PL -------- HGB G/DL -------- HCT % -------- mcv FL -------- MCH PG -------- mmc % -------- PLT X10'/,WL -------- RETIC t -------- RET X103/,u ----- 0 MEAN 6.23 12.3 40.2 64.9 19.9 30.6 572 .4 S.D. .766 .66 3.27 4.33 1.87 1.01 74.6 .22 m 6 6 6 6 6 6 6 6 0.03 MEAN 6.48 12.0 40.2 62.4 18.5 29.7 462 .4 S.D. .593 .83 2.39 6.25 2.02 .67 83.8 .37 m 4 4 4 4 4 4 4 4 - 0.15 MEAN 7.00 12.8 42.3 60.5 18.3 30.3 436 .4 S.D. 1.068 2.17 6.70 2.31 .76 .57 133.5 .28 N 6 6 6 6 6 6 6 6 0.75 MEAN 6.28 11.8 40.2 64.0 18.9 29.5 504 .3 SN.D. .3967 .629 1.966 1.267 .672 .670 1486.3 .625 90 Table 10 Summary of Clinical Hematology Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ wpc X10 /,uL -------- N-SEG X103/,UL -------- LYMPH X103/,uL -------- MONO X10'/.uL -------- EOIIN XIO /liL -------- BASO X103/,UL -------- N-SEG% -------- LYMPH% -------- MONO% -------- ROS ---- 0 MEAN 11.1 5.8 4.3 .6 .3 .0 50 40 6 .48 .18 .08 17.6 15.9 4.6 S.D. 2.93 3.08 1.73 N 6 6 6 6 6 6 6 6 6 0.03 MEAN 8.7 4.4 3.4 .6 .2 .0 50 40 8 S.D. N 1.42 .4 1.59 4 1.16 .4 .13 .17 4 4 o6 14.5 14.9 .5 4 4 4 4 0.15 MEAN 8.8 4.3 3.6 .5 .3 .0 48 42 6 -NS.D. 1.768 1.765 .963 .16 6 .16 5 .605 136.1 161.2 26.9 0.75 MEAN 9.3 5.6 3.0 .6 .1 .0 56 36 7 .40 .08 .05 13.2 14.2 2.7 S.D. 4.59 3.89 1.07 N 6 6 6 6 6 6 6 6 6 91 Table 11 Summary of Clinical Hematology Data males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOT.GUS MONKEYS ACID DOSE mg/kg/day ------ RPC X10 /,uL -------- HGB G/DL -------- HCT t -------- mcv FL -------- MCH PG -------- MCHC t -------- PLT X10'/,wL -------- RETIC t RE X103 /A -------- ---- 0 MEAN 6.43 12.4 40.3 62.8 19.3 30.7 490 .3 S.D. .314 .53 2.17 3.11 1.06 1.00 124.3 .26 N 6 6 6 6 6 6 6 6 0.03 MEAN 7.00 12.7 42.5 61.0 18.2 29.6 512 .7 S.D. .628 .55 1.78. 3.13 1.02 .43 208.8 .54 N 4 4 4 4 4 4 4 4 0.15 MEAN 6.50 12.3 40.4 62.1 19.0 30.6 496 .5 S.D. .295 .16 .93 2.53 .76 .49 82.6 .54 N 6 6 6 6 6 6 6 6 0.75 MEAN 6.66 12.2 41.0 61.6 18.2 29.6 431 .4 S.D. .488 .01 2.23 2.47 .77 .65 198.6 .19 N 6 6 6 6 6 .6 6 6 92 Table 11 Summary of Clinical Hematology Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH I?ERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ W-F Xio /IAL N SEG xio 3 /PL -------- -------- LYMPH X103 /,UL -------- MONP X10 /,uL -------- DO.IIN X10 IA&L -------- BASO XIO'/t4L -------- N-SBG% -------- LYMPH& mmt -------- -------- ROSIN ------ 0 MEAN 6.7 2.4 3.7 .4 .1 .0 37 55 6 S.D. 1.99 .64 1.24 .16 oe .04 4.1 2.8 2.1 N 6 6 6 6 6 6 6 6 6 0.03 MEAN 8.5 4.4 3.3 .6 .2 .0 50 40 7 NS.D. 1.640 1.749 .488 .400 .410 .400 143.9 124.6 14.0 0.15 KEAN 10.3 5.7 * 3.7 .6 .2 .0 56 36 7 S.D. 3.21 1.85 1.61 .27 .18 .05 N 6 6 6 6 6 6 9.3 8.4 2.6 6 6 6 0.75 MEAN 9.4 5.1 * 3.5 .6 .2 .0 52 38 6 S.D. N 2.56 6 2.06 6 .71 .28 6 6 .16 .05 6 6 9.8 7.8 3.2 6 6 6 93 Table 11 Summary of Clinical Hematology Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWS SULFOWIC POTASSIUM SALT (PFOS; T-6295) IW CYNOWOLOGUS WONKEYS ACID bose mg/kg/day ------ Rpc X10 /,WL HGB G/DL -------- -------- HCT mcv t PL -------- -------- MCH MCHC PG t -------- -------- PLT X103/IAL -------- RETIC t RETIC X103/,uL -------- ------- 0 MEAN 6.31 12.3 40.3 64.1 19.5 30.4 562 .3 2 S.D. .565 .77 2.79 3.90 1.21 .33 83.6 .08 N 6 6 6 6 6 6 6 6 0.03 MEAN 6,.20 11.7 39.2 63.6 19.0 29.9 467 .5 3 S.D. .472 .97 2.18 7.19 2.78 1.21 33.4 .13 N 4 4 4 4 4 4 4 4 0.15 MEAN 6.50 12.0 39.4 60.7 18.6 30.6 442 .2 1 S.D. .298 .42 1.44 2.35 .78 .57 78.9 .10 N 6 6 6 6 6 6 6 6 0.75 MEAN 6.32 11.9 40.3 63.8 18.8 29.4 504 .2 S.D. .210 .36 1.54 1.37 .51 .54 124.1 .15 N 6 6 6 6 6 6 6 6 94 Table 11 Summary of CliniCal Hematology Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH @ERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS: T-6295) Iki CYNOMOLGUS W)NKEYS DOSE mg/kg/day ------ X10WPC/,uL N-SEG LYVPH X10'/.UL X10'/;AL M?!p BOJIN BASO X10 /,uL X10 /,uL X10'/ML N-SEG% LYMPH% Homo% BOSIN% -------- -------- -------- -------- -------- -------- -------- -------- -------- ------- 0 MEAN 9.4 4.0 4.3 .6 .4 .0 44 46 7 S.D. 1.89 i.31 1.59 .10 .27 .04 12.5 10.3 1.0 N 6 6 6 6 6 6 6 6 6 0.03 MEAN 6.7 4.4 3.2 .8 .2 .0 48 39 9 S.D. 3.42 2.74 1.22 .41 .10 .10 13.2 11.2 3.9 N 4 4 4 4 4 4 4 4 4 0.15 MEAN 8.7 4.4 3.4 .6 .2 .0 51 39 7 S.D. 1.25 .82 .69 .18 .12 .00 6.4 6.6 1.5 N 6 6 6 6 6 6 6 6 6 0.75 MEAN 8.1 4.6 2.9 .6 .1 .0 56 36 7 S.D. 1.91 1.75 1.02 .26 .08 .05 13.1 10.4 3.5 N 6 6 6 6 6 6 6 6 6 95 Table 12 Summary of Clinical Hematology Data males Day 153 26-WEEK CAPSULE TOXICITY STUDY VIITH IERFLUDROOCTANK SULFONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ RPC X10 /,uL -------- HGB G/DL -------- HCT t -------- mcv FL -------- @NCH PG -------- MCHC t -------- PLT X10'/,uL -------- RETIC RETIC X103/,uL -------- ------- MEAN S.D. N 0.03 KEAN S.D. N 0.15 mm S.D. N 0.75 MEAN S.D. N 6.68 .421 6 7.08 .513 4 6.78 .479 6 6.65 .641 6 12.5 .54 6 12.6 .46 4 12.6 .38 6 11.8 1.04 6 40.9 2.28 6 41.7 1.91 4 41.3 1.47 6 40.0 3.32 6 61.4 2.74 6 59.0 2.70 4 61.1 2.82 6 60.3 2.43 6 18.7 .88 6 17.8 .90 4 18.7 .95 6 17.7 .87 6 30.6 .62 6 30.2 .82 4 30.@ .40 6 29.4 .50 6 464 131.6 6 483 167.0 4 519 146.4 6 398 199.1 6 .2 1 .26 1 6 .2 .16 & .4 .15. 6 .6 .48 6 96 Table 12 Summary of Clinical Hematology Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH IORPLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID DOSE mg/kg/day ------ WPC XIO /,uL -------- N-SEG X10'/,UL -------- LYMPH X10'/,UL -------- MONO X10'/,UL -------- EOSIN X10'/,uL ----- -- BASO X10'/.UL N-SEG% -------- -------:- LYMPH% MONO% ROSIN% -------- -------- -------- 0 MEAN 7.3 2.7 3.9 .5 .2 .0 35 54 7 1 S.D. 2.62 1.64 .91 .29 .15 .08 8.6 9.3 2.9 2 N 6 6 6 6 6 6 6 6 6 6 0.03 MEAN S.D. N 9.9 1.04 4 5.6 1.70 4 3.5 1.08 4 .6 .2 .0 56 36 .22 .08 .00 15.0 13.5 4 4 4 4 4 6 2 1.8 1 4 4 0.15 49 42 2 MEAN S.D. 10.1 2.44 5.2 2.81 4.0 1.17 .7 .12 .3 .21 .0 .05 18.2 16.4 2.5 2 N 6 6 6 6 6 6 6 6 6 6 0.75 MEAN 9.0 4.3 3.6 .8 .2 .0 45 44 9 2 S.D. 2.87 3.02 1.08 .44 .18 .04 16.3 16.1 3.7 1 N 6 6 6 6 6 6 6 6 6 6 97 Table 12 Summary of Clinical Hematology Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULFONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ Rpc HGB HCT mcv X10 /,uL G/DL % FL -------- -------- -------- ------- MCH PG ------- MCHC PLT RLPTIC RETIC % X10'/,uL t X10'/,uL -------- -------- -------- ------- 0 MEAN 6.60 12.4 40.6 61.7 18.8 30.6 520 .4 2 S.D. .559 .85 2.96 2.45 .77 .46 73.1 .31 2 N 6 6 6 6 6 6 6 6 0.03 MEAN 6.66 12.0 40.4 61.1 18.1 29.6 3857 .6 3 S.D. .641 .92 2.44 6.52 2.23 .82 2.3 .61 3 N 4 4 4 4 4 4 4 4 0.15 MEAN '6.66 12.1 39.9 59.8 18.2 30.4 460 .3 2 S.D. .257 .45 1.31 2.12 .64 .18 83.7 .24 1 6 6 6 6 6 6 6 6 0.75 MEAN 6.33 11.7 39.5 62.4 18.5 29.7 492 .2 1 S.D. .288 .44 1.98 2.21 .70 .65 144.0 .12 N 6 6 6 6 6 6 6 6 98 Table 12 Summary of Clinical Hematology Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH-PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ W PC X10 /,uL -------- N-SEG X10'/,uL -------- LY@IPH X10 /.UL -------- MONO X10'/.uL EO@@IN , BASO X10 /,uL XiolIjAL -------- -------- -------- N-SEG% -------- LYMPH!K -------- MONO% -------- ROSIN% ------- 0 MEAN S.D. N 9.7 2.44 6 4.6 2.98 6 4.1 1.08 6 .8 .2 .0 44 44 9 .30 .18 .05 18.7 15.9 3.9 6 6 6 6 6 6 0.03 1 MEAN 9.3 5.0 2.9 1.1 .2 .1 50 36 11 NS.D. 4.449 3.545 .462 1.040 .414 .408 142.6 154.6 34 .6 0.15 MEAN 8.1 3.7 3.4 .6 .3 .0 44 44 8 .14 .15 .00 14.5 14.4 2.2 S.D. 2.23 1.99 .96 N 6 6 6 6 6 6 6 6 6 0.75 MEAN 9.5 4.4 4.0 .8 .2 .0 46 43 9 SN.D. 2.969 2.363 2.169 .365 .163 .06 5 176.4 166.5 46 .3 99 Table 13 Summary of Clinical Hematology Data males Day 192 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTME SULFONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ 0 MEAN S.D. N 0.03 MPAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. RBC xi06 /,uL -------- 6.60 .354 6 6.96 .627 4 6.65 .372 6 6.32 .387 4 HGB G/DL -------- HCT t -------- 12.5 .50 6 12.5 .45 4 12.5 .31 6 11.4 .83 4 41.1 2.07 6 42.1 1.79 4 41.0 1.15 6 38.8 2.45 4 mcv FL -------- 62.3 2.53 6 60.7 2.81 4 61.8 2.76 6 61.5 2.72 4 MCH PG -------- MCHC t -------- PIT xio3 /,uL -------- RETIC t -------- RETIC 03 xi /)jL ------- 18..978 30..379 46970.4 ..208 1 6 6 6 6 16.0 29.6 466 .2 1 1.05 .88 183.0 .17 1 4 4 4 4 18.8 30.4 470 .3 19 .80 .30 63.1 .04 3 6 6 6 6 6 17.9 29.2 401 .2 12 1.08 .48 228.0 .24 14 4 4 4 4 4 Table 13 Summary of Clinical Hematology Data Females , Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SUTFONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS MONKKYS ACID DOSE mg/kg/day ------ RBC HGB HCT mcv MCH MCHC PIT RETIC RETI X106/.uL G/DL t FL PG .% X103/,uL t X10'/,uL -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 14EAN 6.40 12.1 40.8 63.9 19.0 29.7 484 .4 S.D. .461 .64 2.67 2.49 .70 .65 100.1 .24 N 6 6 6 6 6 6 6 6 0.03 MEAN 6.15 11.2 38.3 62.3 18 2 29.3 429 .2 S.D. .798 1.66 5.67 6.23 2:og .94 54.7 .13 N 4 A 4 4 4 4 4 4 0.15 MEAN 6.57 11.9 39.9 60.8 18 2 29.9 412 .2 S.D. .256 .62 1.70 2.50 :73 .35 74.4 N 6 6 6 6 6 6 6 6 0.75 MEAN 6.09 11.3 39.2 64.3 18.6 29.0 490 .2 S.D. .360 .37 2.17 1.46 .71 1.09 166.0 .21 N 6 6 6 6 6 6 6 6 102 Table 13 Summary of Clinical Hematology Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ WBC X10'/,uL -------- N-SEG xi03 /,uL -------- LYIPH XIO /,wL -------- MONO Xlol/,uL -------- BOSIN X103 /,uL -------- BASO X10'/.UL -------- N-SEG% -------- LYMPH% -------- MONO% -------- EOSI ---- 0 MEAN 10.4 53..401 41..396 ..715 ..219 ..005 4167.5 d1a5.1 83.4 S.D. 3.59 N 6 6 6 6 6 6 6 6 6 0.03 MEAN 8.5 4.3 3.2 .7 .3 .0 50 38 8 S.D. 2.05 1.45 .57 .32 .15 .10 9.3 10.1 2.2 N 4 4 4 4 4 4 4 4 4 0.15 KEAN 9.2 4.5 3.8 .6 .3 .0 48 43 6 S.D. 1.61 1.73 .61 .18 .24 .04 13.0 11.7 2.1 N 6 6 6 6 6 6 6 6 6 0.75 MEAN 9.7 4.2 4.6 .7 .2 .1 46 45 8 S.D. 2.73 1.10 2.70 .32 .08 .05 14.6 14.8 3.4 N 6 6 6 6 6 6 6 6 6 103 26-WEEK Table 14 Summary of Clinical Hematology Data Males Day 217 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ RBC X106/,uL -------- HGB G/DL -------- HCT mcv FL -------- -------- MCH MCHC PG -------- -------- PLT Xi 03 /,UL -------- RETIC TM xi0 /,u -------- ----- 0 MEAN 6.26 12.0 30.1 60..835 19..128 31..535 418933.7 ..047 SN.D. .0027 .221 .228 2 2 2 2 2 0.15 MEAN 6.49 12.7 40.7 62.8 19.6 31.2 488 .3 S.D. N .057 2 .42 1.27 2 2 1.34 2 .42 .07 118.8 .14 2 2 2 2 0.75 MEAN 5.90 11.6 37.8 64.0 19.5 30.6 469 .4 NS.D. .0422 .207 .62 4 .72 1 .027 .422 222.6 .221 104 26-WEEK Table 14 summary of Clinical Hematology Data males Day 217 CAPSULE TOXICITY STUDY WRTH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ WBC X10.1/,uL -------- N-SEG Xlol/jL -------- LYMPH X10'/,WL -------- MONO X10'/,uL -------- EOSIN X10'/,UL -------- BAIO Xl 0 /,uL -------- N-SEG% -------- LYMPH% -------- MONO% -------- HosiN ------ 0 MEAN 7.3 2.4 4.0 .6 .2 .0 34 54 9 S.D. 1.70 .14 1.63 .14 .07 .00 N 2 2 2 2 2 2 4.9 9.9 4.2 2 2 2 0.15 MEAN 11.5 6.2 4.5 .6 .3 .0 53 38 6 .21 .14 .00 .0 5.7 3.5 S.D. 3.82 2.05 2.12 N 2 2 2 2 2 2 2 2 2 0.75 MEAN 11.0 6.0 4.4 .9 .4 .0 50 39 7 .57 .07 .00 5.7 7.1 2.8 SN.D. 4.120 2.629 .278 2 2 2 2 2 2 105 26-WEEK Table 14 Summary of clinical Hematology Data Females Day 217 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day RSC X106 /,uL -------- HGB G/DL -------- HCT t -------- mcv FL -------- MCH PG ----- -- MCHC t -------- PLT X103 /,uL -------- RETIC t -------- xlo,/)' ----- 0 MEAN 5.94 11.8 36.9 62.0 19 8 32.0 468 .3 S.D. .714 1.20 4.81 .64 :35 2 .99 111.0 .28 2 2 2 N 2 2 2 2 0.15 MEAN 6.14 11.9 37.6 61.4 19.5 31.7 .14 408 37.5 .4 .21 .092 .14 .57 .027 .027 2 2 2 S.D. N 2 2 2 0.75 MEAN 6.42 12.0 40.2 62.6 18.7 29.8 1.34 444 160.5 .5 .20 S.D. .417 .28 2.920 .257 .271 2 2 2 N 2 2 106 26-WEEK Table 14 Summary of CliniCal Hematology Data Females Day 217 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLOUS ACID DOSE mg/kg/day ------ X10 /.UL -------- N-SEG X103/ML -------- LYMPH X103/,uL -------- MONP XIO /liL EO.@IN X10 /jAL -------- -------- BA@o X10 ImL N-SEG% -------- -------- LYMPH% -------- MONO% -------- EOSI ----- 0 MEAN 8.2 4.6 2.8 .6 .1 .0 55 7.1 36 7.8 a .7 NS.D. 2.726 2.122 .235 .228 .200 .200 2 2 2 0.15 MEAN 7.6 2.6 4.0 .6 .4 .0 34 53 8 .07 10.6 11.3 2.8 1.06 1.20 .35 .124 .221 2 2 2 2 S.D. N 2 2 2 0.75 MEAN S.D. N 9.3 2.26 2 2.6 .64 2 5.8 1.20 2 .6 .2 .0 28 64 6 .35 .07 .07 2 2 2 .7 2.1 2.8 2 2 2 107 Table 15 Summary of CliniC&l Hematology Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTAM SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLOGUS ACID DOSE mg/kg/day ------ RPC XIO /,uL ------ - HGB HCT mcv MCH MCHC fLT RETIC RETI G/DL t FL PG t X10 /,UL t X10'/,UL -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN 6.52 12.6 39.2 60.2 19.4 32.1 556 .2 S.D. .332 .57 1.91 .07 .07 .00 181.7 .14 N 2 2 2 2 2 2 2 2 0.15 MEAN 6.78 13.3 42.2 62.1 19.6 31.6 493 .2 S.D. .049 .00 .49 1.13 28 .21 36.8 .07 N 2 2 2 2 2 2 2 2 0.75 MEAN 6.20 11.9 39.5 63.7 19.2 30.1 532 .6 S.D. .191 .71 .64 .99 49 1.27 43.1 .28 N 2 2 2 2 2 2 2 2 108 26-WEEK Table 15 summary of Clinical Hematology Data Males Day 245 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ----- X1W0PC/;iL N-SEG LYMPH Xi 03 /,uL X10'/mL MONP EO.@IN RA 0 X10 /,uL X10 /,uL Xloq /14L N-SEG% LYMPH% MONO% ROS -- ----- ------- ---------------- -------- -------- -------- -------- -------- ---- 0 MEAN 10.0 3.2 6.1 .4 .3 .0 32 60 4 .00 1.4 3.5 .7 S.D. 2.90 .78 2.12 .07 .00 2 2 2 2 2 2 2 2 N 2 0.15 ME" 11.4 5.5 4.8 .6 .4 .0 de 42 6 .7 4.9 3.5 SN.D. 1.123 .242 1.026 .228 .207 .200 2 2 2 0.75 MEAN 13.4 5.6 6.2 1.0 .5 .1 41 47 8 5.7 2.1 5.52 2.83 1.77 .64 .14 .00 2 2 2 2 4.2 2 2 2 S.D. N 2 2 109 26-WEEK Table 15 summary of Clinical Hematology Data Females Day 245 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLOUS ACID DOSE mg/kg/day X10RPC/,uL GH/GDBL HtCT mFcLv MPCGH MCHtC X10P'I/TIwL REtTIC xioRlE/IA -------- -------- -------- -------- -------- -------- -------- -------- ----- 0 MEAN 6.22 12.3 38.4 61.6 19.8 32.1 .49 519 82.0 .2 .07 S.D. .735 1.421 4.925 .271 .207 2 2 2 N 2 0.15 MEAN 6.74 12.7 40.7 60.3 18.8 .14 31.2 .28 425 48.1 .2 .07 S.D. .1291 .228 .235 1.227 2 2 2 2 N 0.75 MEAN 6.70 12.5 42.0 62.7 18.7 .71 29.8 1.20 440 149.2 .2 .21 S.D. .453 .42 2.97 .21 2 2 2 2 2 2 2 N 2 110 26-WEEK Table 15 Summary of Clinical Hematology Data Females Day 245 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULPONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ . WBC x 10'/iAL -- ----- N-SEG X103/,UL -------- LYMPH X10-'/,UL MONO X103 /,uL -------- -------- BOSIN X10'/jAL -------- BAIO XIO IJAL -------- N-SEG% -------- LYMPH% -------- MONO% -------- Rosi ---- 0 MEAN 11.4 7.1 3..485 ..728 ..214 ..000 6126.3 3102.0 62.8 S.D. 1.56 2.83 N 2 2 2 2 2 2 2 2 2 0.15 MEAN 9.4 3.0 5.0 1.0 .4 .0 28 56 11 S.D. 2.76 2.97 .49 .00 .28 .07 23.3 21.9 2.8 N 2 2 2 2 2 2 2 2 2 0.75 MEAN 11.0 3.6 6.2 .9 .2 .1 32 56 a SN.D. .221 1.324 1.727 .228 .207 .200 122.7 124.8 22.8 26-WEEK Table 16 Summary of Clinical Hematology Data Males Day 274 CAPSULE TOXICITY STUDY WITH I?ERFLUOROOCTANE SULFOUIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ RPC Xio /,UL HGB G/DL -------- -------- HCT t -------- mcv FL -- ----- MCH PG -------- MCHC t -------- PLT X103/,uL -------- RETIC t oRlET xi liA -------- ----- 0 MEAN 6.72 12.6 40.1 59.6 18.8 .21 31.6 .42 504 228.4 .2 .07 S.D. .198 .49 2.12 1.34 N 2 2 2 2 2 2 2 2 0.15 MEAN 6.78 13..142 421..085 611..598 19..328 31..449 419065.4 ..428 2 2 2 2 S.D. .106 N 2 2 2 2 0.75 MEAN 6.45 121..313 412..040 631..613 19..121 29..992 51690.8 ..314 2 2 2 2 2 S.D. .495 N 2 2 2 112 26-WEEK Table 16 summary of Clinical Hematology Data Males Day 274 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULFONIC POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ WPC X10'/,UL N-FLEG LIPH X10'/,UL XIO /,wL MONP EOSIN RAQO N-SEG% X10 /.uL X103/jiL XIO /,uL LYMPH% Homo% gosi -------- -------- -------- -------- -------- -------- -------- -------- -------- ---- 0 MEAN 7.3 2.628 3..742 ..835 ..100 ..007 366.4 512.8 104.2 2 2 2 2 2 2 S.D. .42 N 2 2 2 0.15 MEAN 11.5 6.6 4.1 .4 .2 .0 58 36 4 6.4 8.5 1.4 S.D. 2.26 2.025 .214 .221 .214 .200 2 2 2 N 2 0.75 MEAN 11.6 5.0 51..941 ..849 ..421 ..007 409.2 499.9 7 .0 2 2 2 2 2 S.D. 6.22, 3.54 N 2 2 2 2 113 26-WEEK Table 16 summary of clinical Hematology Data Females Day 274 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ RPC HGB HCT mcv MCH WHC fLT RETIC RET XIO /,uL G/DL t FL PG t X10 /,uL t xiol/,u -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 6.32 12.3 39.0 61.7 19.5 31.6 510 .4 S.D. 1.082 1.70 7.57 1.41 .71 1.91 135.6 .00 N 2 2 2 2 2 2 2 2 0.15 MEAN 6.64 12.6 40.1 60.3 18.8 31.2 423 .4 S.D. .071 .07 .57 .21 .35 .64 5.7 .21 N 2 2 2 2 2 2 2 2 0.75 MEAN 6.78 12.5 40.8 60.2 18.4 30.5 440 .4 SN.D. .4120 .235 1.526 1.324 .264 .235 1372.9 .235 114 26-WEEK Table 16 summary of Clinical Hematology Data Females Day 274 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANS SULF-OHIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS DOSE mg/kg/day ------ X1W0 PC/,uL -------- N-SEG X103 /,uL ------- LYIPH X10 /,uL MONO xio3 jAL EO.@IN X10 /j4L Bhlo X10 IJAL N-SEG% LYKPH% MONO% BOSI -------- ---------------- -------- -------- -------- -------- ----- 0 MEAN 8.0 5.4 2.8 .5 .0 .0 60 33 6 .00 19.1 15.6 2.9 s D. 1.13 2.420 .299 .214 .207 2 2 2 2 N" 2 0.15 MEAN 7.8 2.9 3.8 .6 .4 .0 34 53 8 .07 22.6 22.6 .7 S.D. 2.26 2.525 .264 .207 .228 2 2 2 2 N 2 0.75 MEAN 9.2 4.4 4.1 .6 .1 .0 48 44 6 .07 2.1 2.1 3.5 S.D. 2.226 .292 .285 .249 .200 2 2 2 2 N 115 26-WEEK Table 17 Summary of Clinical Hematology Data Males Day 322 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTME SULPONIC P(YRASSIUM SALT (PPOS; T-6295) rN CYNOMOLGUS ACID DOSE mg/kg/day RBC HGB HCT mcv MCH MCHC PLT RETIC qw XIO'/,WL G/DL t FL PG t X103/,uL t XIO lAt -------- -------- -------- -- ----- ---------------- -------- -------- ----- 0 MEAN 6.72 12.6 40.2 59.8 18.8 31.5 544 .3 S.D. .078 .35 .57 .07 .28 .42 209.3 .28 N 2 2 2 2 2 2 2 2 0.15 MEAN 6.90 13..257 411..984 611..548 19..449 31..507 49810.6 ..207 S.D. .127 N 2 2 2 2 2 2 2 2 0.75 MEAN 6..21298 11..842 38..135 611..314 19..007 31..071 57423.1 ..365 S.D. N 2 2 2 2 2 2 2 2 116 26-WEEK Table 17 Summary of Clinical Hematology Data Males Day 322 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLOUS ACID DOSE mg/kg/day ------ X10 /,uL -------- N-SEG X10'/,uL LYMPH X103 /,UL -------- -------- MONP EOSIN X10 /liL X103/,uL -------- -------- HA@O X10 liAL -------- N-SEG% -------- LYMPH% -------- xm t -------- EOSI ----- 0 MEAN 8.6 4.2 3.8 .6 .1 .0 48 42 8 4.9 6.4 1.4 S.D. 1.20 .21 1.06 .07 .200 .200 2 2 2 N 2 2 2 2 0.15 MEAN 12.8 82..025 3..799 ..821 ..207 ..000 649.2 3100.6 61.4 2 2 2 2 2 S.D. 1.34 N 2 2 2 2 0.75 MEAN 9.0 4.0 3.9 .8 .2 .0 43 44 10 S.D. 3.75 2.55 1.13 .07 .07 .07 N 2 2 2 2 2 2 9.9 6.4 2.8 2 2 2 117 26-WEEK Table 17 Summary of Clinical Hematology Data Females Day 322 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNONOLGUS ACID DOSE mg/kg/day ------ RBC Xlol/,UL -------- HGB G/DL -------- HCT t -------- mcv FL -------- MCH PO -------- MCHC t -------- PLT X103/,wL -------- RETIC t RET xiol/jA -------- ----- 0 MEAN 6.32 12.3 38.4 2.12 60.8 .49 19.6 .21 32.1 .07 546 140.0 .2 .14 S.D. .403 .64 N 2 2 2 2 2 2 2 2 0.15 MEAN 6.76 12.5 40.1 .,78 59.4 1.77 18.4 .21 31.0 .64 472 103.9 .4 .07 S.D. .071 .00 N 2 2 2 2 2 2 2 2 0.15 MEAN 6.50 11.9 39.5 60.8 18.4 30.2 .71 424 155.6 .3 .20 SN.D. .4231 .242 2.219 .264 .264 2 2 2 118 26-WEEK Table 17 Summary of Clinical Hematology Data Females Day 322 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ----- XIOWPC/,uL -- ----- N-SEG xio '/,UL LYMPH X10'/,uL MONO X10'/,UL EOSIN X101/,wL RAQO X10 IIAL N-SEG% LYMPH% MONO% EOSI -------- -------- -------- -------- -------- -------- -------- -------- ----- 0 MEAN 11.8 7.2 3.2 1.0 .2 .0 59 30 8 11.3 11.3 2.1 4.38 3.96 .07 .257 .207 .200 2 2 2 S.D. N 2 2 2 0.15 MEAN 9.4 4.2 4.2 .6 .4 .0 42 49 7 21.2 19.1 4.2 3.18 .42 .221 .228 .200 2 2 2 S.D. 2.83 N 2 2 2 0.75 MEAN 8.9 2.7 5.6 .6 .2 .0 30 62 6 1.4 .7 .57 .78 .07 .07 .00 2 2 1.4 2 2 2 S.D. 1.56 N 2 2 2 2 119 26-WEEK Table 18 Summary of Clinical Hematology Data Males Day 364 CAPSULE TOXICITY STUDY MITH IERFLUOROOCTAME SULFOMIC POTASSIUM SALT (PFOS; T-6295) IM CYNOMOLGUS ACID DOSE mg/kg/day RBC HGB HCT X10'/)AL G/DL % mcv MCH MCHC PLT FL PG t XIO'/IAL -------- -------- -------- -------- -------- -------- -------- RETIC % Xio /.UL ----- ----- 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MP" S.D. N 6.53 .042 2 6.72 .283 2 6.23 .198 2 12.4 .07 2 13.0 .64 2 12.2 .21 2 39.5 .07 2 41.2 2.97 2 38.9 .28 2 60.5 .49 2 61.3 1.91 2 62.5 2.40 2 19.2 .21 2 19.4 .28 2 19.5 .28 2 31.6 .07 2 31.7 .57 2 31.2 .85 2 514 179.6 2 448 68.6 2 Soo 17.7 2 .1 .14 2 .1 .14 2 .8 1.06 2 120 26-WEEK Table 18 Summary of Clinical Hematology Data males Day 364 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULF-ONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOTGUS DOSE m-g-/k-g-/-da-y WBC X10'/,uL -------- H-SEG X10'/,uL LYMPH X10'/ML -------- -------- mono X10 /,uL -------- EOFIN BASO XIO /jwL XI 0'/,WL -------- -------- N-SEG% -------- LYMPH% MONO% -------- -------- BOSIN ------ 0 MEAN 10.8 6.6 3.4 .7 .0 .0 61 32 6 S.D. N .14 .99 .92 .14 .07 .07 2 2 2 2 2 2 8.5 9.2 .7 2 2 2 0.15 mm 12.5 8.2 3.5 .8 .1 .0 64 28 6 .49 .14 .00 6.4 10.6 2.8 S.D. 1.84 1.99 .71 N 2 2 2 2 2 2 2 2 2 0.75 MEAN 12.2 6.4 4..278 1..142 ..407 ..007 524.9 365.7 9 .0 S.D. 3.96 2.69 N 2 2 2 2 2 2 2 2 2 121 26-WEEK Table 18 Summary of Clinical Hematology Data Females Day 364 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULFIONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS DOSE mg/kg/day ------ RPC X10 /.uL -------- HGB G/DL -------- HCT -------- mcv FL -------- MCH PG -------- MCHC -------- PLT X10'/,WL -------- RETIC t xio /I -------- ---- 0 MEAN 6.28 12.4 38.1 60.8 19.8 32.6 534 .2 S.D. .453 .78 2.90 .35 .14 .42 142.8 .07 N 2 2 2 2 2 2 2 2 0.15 MEAN 6.77 12.6 AO.8 60.2 18.6 31.0 456 2 S.D. .113 .14 1.34 .92 .07 .64 67.9 .07 N 2 2 2 2 2 2 2 2 0.75 MEAN 6.54 12.2 40.1 61.3 18.6 30.4 449 .2 S.D. .028 .07 .57 1.13 .14 .78 181.7 .07 N 2 2 2 2 2 2 2 2 122 26-WEEK Table 18 Summary of Clinical Hematology Data Females Day 364 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ WBC X10'/IAL -------- N-EG X10 /,UL -------- LY_PPH X10 /,uL -------- moqo X10 lAiL -------- BOSIN BASO X10'/,uL XI 0'/14L -------- -------- N-SEG% -------- LYMPH% -------- umt -------- ROS ---- 0 MEAN 7.4 3.4 2.8 1.0 .2 .0 46 37 14 S.D. 1.48 1.13 .42 .28 .14 .00 6.4 1.4 6.4 N 2 2 2 2 2 2 2 2 2 0.15 MEAN 8.1 3.0 3.7 .9 .4 .0 38 46 11 S.D. .57 .71 .99 .42 .14 .07 10.6 9.2 4.2 N 2 2 2 2 2 2 2 2 2 0.75 MEAN 10.8 4.7 5.2 .8 .1 0 43 48 8 S.D. .78 .57 .21 .42 .14 .00 1.4 4.9 3.5 N 2 2 2 2 2 2 2 2 2 123 26-WEEK Table 19 Summary of Clinical Hematology Data males Day 456 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ RBC X10'/.uL ------- GH/GDBL H%CT mFcLv MCPHG MC%HC XIOP'L/T.uL RE%TIC xio /,u -------- ---------------- -------- -------- -------- -------- ----- 0 MEAN 6.63 12.9 40.2 60.7 19.4 .00 32.0 .28 460 174.7 .3 .14 S.D. .269 .57 1.34 .42 2 2 2 2 2 2 2 N 2 0.15 MEAN 7.16 14.0 45.6 63.7 19.5 30.6 .21 490 106.8 .3 .28 SN.D. .0249 .221 .299 .292 .214 2 2 2 0.75 MEAN 6.30 12.6 40.6 64.5 19.9 .21 31.0 .14 510 92.6 .7 .99 S.D. .530 2 .92 2.69 1.13 2 2 2 2 2 2 2 N 124 Table 19 summary of Clinical Hematology Data males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH JERFLUOROOCTAKE SULFMIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ WBC X10'/.UL N-SEG X10'/,UL --- ---- ------- LYMPH X10'/,UL mo no EOPIN BASO X10 /,uL xio /,uL Xio 3/)iL N-SEG% LYMPH% Homo% BOSI ---------------- -------- -------- -------- -------- -------- ---- 0 MEAN 11.6 6.4 4.4 .6 .1 .0 55 38 6 .07 9.9 9.5 .7 S.D. .57 1.428 .278 .207 .200 2 2 2 2 N 2 0.15 MEAN 11.6 4.9 5.9 .6 .2 .0 42 50 6 .00 4.9 2.1 2.1 S.D. 1.27 1.13 .42 .21 .00 2 2 2 2 2 2 2 N 2 2 0.75 MEAN 16.6 10.3 4.8 1.2 .4 .1 62 28 6 .7 .7 .7 S.D. 6.51 3.926 1.727 .264 .221 .200 2 2 2 N 2 125 26-WEEK Table 19 Summary of Clinical Hematology Data Females Day 456 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kglday ----- RPC X10 /,uL HGB G/DL -------- -------- HtCT NFCLV MCPHG MCtHC X10P'L/T,uL REtTIC Xlo'R/E,TUICL ------- -------- -------- -------- -------- -------- ------- 0 MEAN 6.26 12.4 38.5 61.6 19.8 .35 32.2 .49 494 122.3 .5 .14 S.D. ..884 1.56 5.23 .35 2 2 2 2 2 2 2 N 2 0.15 MEAN 6.66 12.7 40.8 61.4 19.2 31.2 .78 451 14.1 .3 .14 S.D. .064 .00 .285 .271 .221 2 2 2 N 2 2 0.75 MEAN 7.06 13.1 42.9 60.8 18.S .78 30.6 .92 446 215.7 .2 .21 S.D. .629 .57 3.18 .92 2 2 2 2 2 2 2 N 2 126 26-WEEK Table 19 Summary of Clinical Hematology Data Females Day 456 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTME SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNO14OLGUS ACID DOSE mg/kg/day ------ WBC N-SEG LYMPH mo,_qo EPOSIN BASO N-SBG% LYMPH% MONO% Rosi -X-l-o'-/-,U-L- --Xl-W-l-j-AL-- -X-1-01-/-,-uL----XI-O--/,-u-L- -X-I-O-'/-j-j-L-X-10-'-/-)A-L--- -------- -------- -------- ----- 0 MEAN 8.8 4.4 3..464 ..714 ..314 ..000 506.4 383.5 8 .7 2 2 2 2 S.D. .78 .14 N 2 2 2 2 2 0.15 MEAN 9.9 31..870 4..607 ..914 ..268 ..000 3171.3 486.4 9 .0 2 2 2 2 2 S.D. 1.70 N 2 2 2 0.75 MEAN 10..692 3..071 61..526 1..007 ..314 ..207 299.9 589.9 91.4 S.D. N 2 2 2 2 2 2 2 2 2 127 26-WEEK Table 20 Summary of Clinical Hematology Data Males Day 546 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULPONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ RBC HGB HCT mcv MCH MCHC PIT RETIC Fmi X10'/,uL G/DL t FL PG t X10'/14L t xio /,uL -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN 6.56 12.6 40.7 61.9 19.2 31.0 434 .5 S.D. .035 .00 1.06 1.27 .07 .71 96.9 .28 N 2 2 2 2 2 2 2 2 0.15 MEAN 6.90 13.6 43.9 63.6 19.8 31.1 373 .7 S.D. .141 .21 .42 .71 .00 .28 5.7 .00 N 2 2 2 2 2 2 2 2 0.75 MEAN 6.42 12.6 42.4 66.0 19.6 29.6 520 .6 S.D. .000 .14 1.56 2.33 .14 .78 59.4 .42 N 2 2 2 2 2 2 2 2 128 Table 20 Summary of Clinical Hematology Data males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM 9ALT (PFOS: T-6295) IN CYNO14OLGUS DOSE mg/kg/day ------ WBC X10'/ML N-SEG LYMPH Xlol/,UL X10'/,UL moqo ZOPIN BASO X10 /.UL X10 /,UL X10'/,UL N-SRG% LYMPH% momot BOSIN --- ---- -------- -------- -------- -------- ---------------- -------- -------- ------ 0 MEAN 8.4 3.1 4.2 .8 .1 .2 36 52 9 .21 11.3 12.0 2.8 S.D. 1.77 1.526 .214 .242 .200 2 2 2 2 N 2 0.15 MEAN 10.9 5.0 4.7 .8 .4 .1 46 42 0 1.4 4.2 4.2 S.D. 3.96 1.720 2.122 .214 .221 .200 2 2 2 N 2 0.75 MEAN 16.0 9.8 4.4 1.2 .2 .2 62 28 8 .14 11.3 7.8 .7 S.D. .35 1.48 1.41 .07 .21 2 2 2 2 2 2 2 N 2 2 129 26-WEEK Table 20 Summary of Clinical Hematology Data Females Day 546 CAPSULE TOX ICITY STUDY WITH IERFLUOROOCTANE SULFMIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLOUS ACID DOSE mg/kg/day ------ RB4C X10 /,uL HGB G/DL -------- -------- HCT mcv MCH MCHC PLT RETIC RETI % FL PG t X10'/,UL t X103/oL ------- -------- -------- -------- -------- -------- ------ 0 MEAN 6.02 11.8 37.5 62.5 19.8 31.6 508 .4 S.D. .700 1.06 4.17 .21 .49 .71 35.4 .21 N 2 2 2 2 2 2 2 2 0.15 MEAN 6.46 12.3 40.2 62.2 19.0 30.6 406 .4 S.D. .191 .42 1.34 .21 .14 .14 2.1 .21 N 2 2 2 2 2 2 2 2 0.75 MEAN 6.72 12.4 40.8 60.8 18.5 30.4 396 .3 S.D. .134 .14 .28 1.56 .57 .14 146.4 .14 N 2 2 2 2 2 2 2 2 130 26-WEEK Table 20 Summary of CliniCal Hematology Data Females Day 546 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ WBC XIO'/,uL -------- N-SEG Xlo,/,UL -------- LYMPH X10'/,UL -------- H(,_)no X10 /iAL -------- EOSIN BASO Xl 0'/,WL X10'/,UL N-SEG% LYMPH% MONO% EOSI -- ----- -------- -------- -------- -------- ----- 0 MEAN 11.2 7.0 2.8 1.0 .3 .2 58 28 10 S.D. 6.15 4.95 .49 .42 .14 .07 12.0 11.3 .7 N 2 2 2 2 2 2 2 2 2 0.15 MEAN 11.5 5.4 4.2 1.0 .6 .2 46 37 10 S.D. 3.25 2.33 1.20 .07 .21 .00 7.1 .0 2.8 N 2 2 2 2 2 2 2 2 2 0.75 .2 30 61 5 MEAN 10.4 3.1 6.4 S .2 S.D. .85 .14 .92 .00 .14 .07 3.5 4.2 .0 N 2 2 2 2 2 2 2 2 2 131 Table 21 summary of Clinical Chemistry Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 UNOL/L CHOL MG/DL -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 HEM 76 20 1.2 9.0 4.9 4.1 .6 S.D. 12.5 3.8 .10 .32 .21 .26 .45 N 6 6 6 6 6 6 6 9 138 2.0 33.7 6 6 0.03 MEAN 70 20 1.2 9.6 5.2 4.4 .4 S.D. 8.3 6.2 .17 .58 .46 .48 .18 N 4 4 4 4 4 4 4 9 110 1.4 20.1 4 4 0.15 MEAN S.D. N 82 30.4 6 21 3.3 6 1.2 .22 6 9.5 .44 6 5.1 .34 6 4.4 .26 6 .6 10 151 .37 2.2 26.1 6 6 6 0.75 MEAN 73 20 1.3 9.4 5.2 4.3 .5 S.D. 1S.4 2.0 .11 .38 .28 .37 .29 N 6 6 6 6 6 6 6 9 130 1.3 29.3 6 6 132 Table 21 Sumnary of Clinical Chemistry Data males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L ANYLASE IU/L LIPASE ZU/L P AM U/L -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 0.03 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N MEAN S.D. N 56 16.5 6 44 6.3 4 72 23.5 6 68 11.7 6 32 9.7 6 36 11.2 4 69 35.7 6 80 54.2 6 711 252.6 6 700 265.6 4 770 210.3 6 840 360.9 6 134 42.8 6 141 34.5 4 160 68.4 6 171 53.3 6 7 1133 1.9 535.3 6 6 3 936 1.0 709.0 4 4 8 1087 5.4 322.3 6 6 6 1094 1.5 497.4 6 6 395 93.4 6 476 164.6 386 94.S 6 529 135.6 6 55 2 04.4 6 35 3 20.6 1 4 51 2 42.4 6 di 3 31.8 6 133 Table 21 Summary of Clinical chemistry Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLOUS SULFOUIC MONKEYS ACID DOSE mg/kg/day ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- 0 MEAN 10.8 S.D. .60 N 6 6.2 .84 6 159 4.6 6 5.4 .58 6 109 2.9 6 0.03 0.15 MEAN S.D. N MEAN S.D. 0.75 MEAN S.D. N 11.6 .53 4 11.5 .62 6 11.3 .54 6 6.6 .44 4 7.1 .99 6 6.9 1.06 6 164 6.0 4. 163 5.3 6 161 4.6 6 5.9 .32 4 6.4 .60 6 5.8 .62 6 ill 2.2 4 112 2.7 6 100 2.9 6 134 Table 21 summary of clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH IERPLUOROOCTAWE 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 UNOL/L -------- CHOL MG/DL -------- 0 MEAN 76 22 1.2 9.6 4.9 4.7 .5 S.D. 22.2 1.6 .08 .78 .35 .83 .34 N 6 6 6 6 6 6 6 7 149 1.9 37.2 6 6 0.03 MEAN 73 22 1.2 9.3 4.7 4.6 .5 S.D. 10.7 1.3 .08 .50 .18 .41 .17 N 4 4 4 4 4 4 4 6 130 1.7 12.4 4 4 0.15 MEAN 76 23 1.1 9.6 4.7 4.9 .6 12 144 S.D. 12.0 3.9 .10 .62 .57 .38 .21 12.1 14.0 N 6 6 6 6 6 6 6 6 6 0.75 MEAN 78 24 1.2 9.4 4.8 4.6 .6 S.D. 16.3 3.9 .19 .79 .40 .65 .37 N 6 6 6 6 6 6 6 9 154 1.4 10.1 6 6 135 Table 21 Summary of Clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH @ERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day ------ AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L OGT IU/L SDH IU/L CK IU/L ANYLASE IU/L LIPASE ZU/L P ANY U/L -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 0.03 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N MEAN S.D. N 64 6.7 6 54 10.2 4 74 35.5 6 72 15.4 6 140 76.9 6 103 29.4 4 110 41.0 6 123 54.2 6 291 130.1 6 201 12.5 4 257 116.5 6 310 141.4 6 123 54.0 6 94 48.5 4 87 32.9 6 75 24.3 6 4 979 1.6 384.3 6 6 3 484 .8 156.7 4 4 4 844 2.4 306.4 6 6 4 1624 2.0 1251.5 6 6 374 121.9 6 378 153.7 4 416 121.0 6 384 88.6 6 28 2 12.5 6 26 2 15.9 4 35 2 21.2 6 19 2 15.4 6 136 Table 21 Summary of Clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295.) IN CYNOMOLGUS SULFOUIC MONKEYS ACID T)OSE mg/kg/day ------ CA MO/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOLIL -------- 0 0.03 0.15 0.75 KEAN S.D. N MEAN S.D. N MEAN S.D. N MEAN S.D. N 11.4 1.10 6 10.9 .58 4 11.0 .59 6 11.3 .59 6 6.2 .63 6 4.7 .99 4 5.9 .78 6 5.5 .50 6 163 7.1 6 163 3.4 4 162 6.1 6 163 4.9 6 6.2 .96 6 5.9 .70 4 6.1 .63 6 6.1 .80 6 lid 5.0 6 115 3.3 4 115 3.1 6 114 1.5 6 137 Table 22 summary of Clinical Chemistry Data males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 UNOL/L CHOL MG/DL -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 60 20 1.1 8.9 4.7 4.2 .8 5.9 3.3 .12 .56 .13 .49 .43 6 6 6 6 6 6 6 62 18 1.2 9.3 5.0 4.3 .4 8.3 3.9 .18 1.02 .46 .85 .16 4 4 4 4 4 4 4 61 21 1.2 9.2 4.8 4.4 .6 9.8 4.9 .23 .33 .25 .32 .27 6 6 6 6 6 6 6 65 21 1.3 9.3 5.1 4.2 .4 7.8 2.3 .12 .37 .36 .40 .17 6 6 6 6 6 6 6 9 140 1.5 22.1 6 6 8 lie 1.3 28.4 4 4 a 146 .8 21.5 6 6 7 130 1.5 18.0 6 6 138 Table 22 Summary of Clinical Chemistry Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME POTASSIUM SALT IPFOSI T-6295) IN CYNOMOLGUS SULFORIC MONKEYS ACID DOSE mg/kg/day ----- 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 ANY U/L -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN S.D. N 45 15.9 6 39 19.5 6 888 339.5 6 134 42.9 6 7 354 2.6 461.0 6 6 374 106.3 6 22 2 12.5 6 0.03 0.15 MEAN S.D. N MEAN S.D. N 37 6.3 4 48 15.9 6 40 13.0 4 50 23.8 6 876 384.3 4 896 267.3 6 120 35.4 4 136 57.3 6 3 191 459 1.5 58.2 149.3 4 4 4 5 184 369 3.2 59.7 78.9 6 6 6 24 2 13.6 4 40 2 21.7 6 0.75 KEAN S.D. N 43 10.0 6 46 23.0 6 996 417.0 6 142 39.9 6 2 283 .4 149.7 6 6 522 124.7 6 26 3 10.9 6 139 Table 22 summary of Clinical ChemistxY Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH VIERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K KNOL/L CL MMOL/L ------- -------- -------- -------- -------- 0 MEAN S.D. N 10.6 .25 6 6.7 .80 6 160 3.6 6 5.4 .28 6 115 3.4 6 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 11.2 1.12 4 11.0 .39 6 10.9 .43 6 6.9 1.58 4 6.8 1.00 6 6.6 1.29 6 165 10.1 4 160 3.1 6 162 3.4 6 5.8 .74 4 5.6 .38 6 5.4 .29 6 116 4.2 4 115 .9 6 114 2.7 6 140 Table 22 summary of clinical Chemistry Data Females Day 37 26-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 UNOL/L -------- CHOL MG/DL -------- 0 0.03 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N MEAN S.D. N se 14.7 6 67 15.2 4 60 8.4 6 70 11.5 6 22 4.4 6 21 3.0 4 20 3.6 6 22 5.4 6 1.1 .16 6 1.1 .05 4 1.0 .04 6 1.1 .14 6 9.3 .71 6 9.0 .41 4 9.2 .26 6 9.1 .31 6 4.4 .26 6 4.5 .15 4.3 .37 6 4.4 .10 6 4.9 .80 6 4.5 .39 4 4.9 .40 6 4.7 .38 6 .6 .34 6 .5 .25 4 .6 .14 6 .4 .15 6 8 .5 6 9 2.5 4 a 3.2 6 7 1.2 6 147 26.9 6 124 11.1 4 133 22.4 6 123 14.1 6 141 Tabl'e 22 Summary of Clinical chemistry Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE POTASSIUM SALT (PPOS: T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L ANYLASE IU/L LIPASE IU/L P ANYI U/L -------- -------- -------- -------- -------- -------- -------- -------- ------- 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 44 12.1 6 49 15.9 4 36 6.6 6 36 8.0 6 59 30.2 6 70 13.3 4 68 30.9 6 46 7.5 6 362 125.6 6 240 48.7 4 319 129.0 6 415 188.9 6 102 42.9 6 88 54.7 4 76 20.3 6 58 20.0 6 5 240 2.4 146.6 6 6 3 378 1.3 262.2 4 4 3 198 1.5 101.3 6 6 2 331 .9 242.1 6 6 339 89.9 6 384 110.9 4 414 115.1 6 373 83.3 6 18 19 13.2 5 6 28 23 15.2 5 4 34 23 17.4 7 6 23 23 5.9 6 6 142 Table 22 summary of Clinical Chemistry Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH OERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K NNOL/L CL MMOL/L -------- --------- -------- -------- -------- 0 0.03 0.15 MEAN S.D. N MEAN S.D. N mm S.D. N 10.4 .39 6 10.2 .42 4 9.7 .73 6 5.7 .73 6 4.2 .37 4 5.1 .6s 6 161 4.9 6 161 5.4 4 157 2.5 6 5.7 .38 6 5.2 .92 4 5.2 .39 6 115 4.4 6 116 4.3 4 114 1.1 6 0.75 MEAN S.D. N 10.4 .25 6 5.0 .48 6 160 5.3 6 5.9 .42 6 116 3.0 6 143 Table 23 Summary of Clinical Chemistry Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYSOMOLGUS SULPONIC MONKEYS ACID DOSE mg/kg/day ------ GLU MG/DL UN MG/DL CRPAT 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 0.03 MP" S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 59 20 1.1 8.6 4.6 4.0 .7 9.1 3.9 .08 .50 .17 .42 .42 6 6 6 6 6 6 6 9 153 1.5 23.0 6 6 59 2.9 4 20 3.7 4 1.2 .14 4 9.0 .69 4 4.7 .36 4 4.3 .58 4 .4 10 114 .10 2.2 25.1 4 4 4 6173.3 183.9 1..219 8..942 4..648 4..144 ..253 101.7 14149.7 6 6 6 6 6 6 6 6 6 74 19 1.3 8.8 4.8 4.0 .3 10 125 10.6 2.6 .12 .41 .53 .59 .06 2.7 20.6 6 6 6 6 6 6 6 6 6 144 Table 23 Sumary of Clinical chemistry Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE 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 MffLASE IU/L LIPASE IU/L 7 ------- -------- -------- -------- -------- -------- -------- -------- P AN ut 0 MEAN S.D. N 36 7.9 6 34 15.2 6 839 321.9 6 130 46.2 6 7 132 371 2.3 27.8 115.8 6 6 6 22 13.9 6 0.03 MEAN S.D. N 35 7.2 4 35 17.5 4 750 369.9 4 li6 25.0 4 A 149 429 1.5 47.7 143.3 4 4 4 21 13.8 4 0.15 MEAN S.D. N 40 9.4 6 37 11.7 6 906 237.9 6 128 39.4 6 5 153 344 3.8 19.9 09.3 6 6 6 20 11.3 6 0.75 MEAN S.D. N 34 6.3 6 43 16.2 6 823 367.0 6 125 29.9 6 3 203 499 .8 57.2 119.4 6 6 22 13.4 6 145 Table 23 Summary of Clinical Chemistry Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANN 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 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.4 .39 6 10.5 .44 4 10.4 .26 6 10.5 .60 6 7.1 .66 6 6.8 .88 4 6.6 1.08 6 6.8 1.31 6 160 2.9 6 166 12.5 4 160 3.5 6 159 6.4 6 5.4 .44 6 5.6 .92 4 5.4 .50 6 5.6 .63 6 120 2.5 6 122 9.3 4 120 3.5 6 120 2.8 6 146 Table 23 Summary of Clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULPONIC ACID POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS MONKEYS 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 UNOL/L CHOL MG/DL ------- --- ---- -------- -------- 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 57 10.2 6 66 17.3 4 62 12.6 6 74 7.2 6 21 .36.5 22 3.4 4 20 2.7 6 20 5.0 6 1.1 .13 6 1.1 .05 4 1.0 .10 6 1.2 .13 6 9.0 .57 6 8.8 .44 4 9.0 .15 6 9.0 .44 6 4.4 .21 6 4.3 .10 4 4.3 .33 6 4.4 .17 6 4.7 .75 6 4.5 .46 4 4.7 .24 6 4.6 .39 6 .5 9 155 .24 .8 45.4 6 6 6 .6 10 127 .26 3.7 11.2 4 4 a .6 10 137 .18 3.2 19.5 6 6 6 .4 9 127 .10 1.9 18.9 6 6 6 147 Table 23 Summary Of Clinical Chemistry Data 26-WEEK Females Day 62 IERFLUOROOCTAM CAPSULE TOXICITY STUDY WITH POTASSIUt4 SALT (PPOS; T-6295) IN CYNOMOLGUS SULPONIC WONMS ACID DOSE mg/kg/day ------ AST/SGOT IU/L -------- ALT/SGPT IU/L ALK PHOS IU/L -------- -------- GC;T iu/L -------- SDH IU/L -------- CK IU/L -------- ANYLPLSE IU/L ------- LIPASS IU/L --- ---- P AWYL U/L ------- 0 0.03 MEAN S.D. N MEHN S.D. N 38 3.4 6 45 9.9 4 53 16.7 6 77 15.9 4 360 152.5 6 241 45.3 4 106 47.7 6 84 44.5 4 41 262 342 1.8 123.6 86.9 6 6 6 4 276 358 2.2 67.9 108.3 4 4 4 14 19 14.7 5 6 19 22 16.7 5 4 0.15 MEAN S.D. N 37 7.8 6 60 29.3 6 305 134.0 6 75 20.8 6 4 194 410 1.0 76.1 129.7 6 6 6 28 23 19.6 8 6 0.75 MEAN S.D. N 31 7.8 6 42 6.2 6 398 200.5 6 58 20.0 6 2 .4 6 243 130.1 6 385 89.4 6 27 2 9 96- 148 Table 23 summary of clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ CA NG/DL I PHOS NO/DL NA MMOL/L x MMOL/L CL NNOL/L -------- -------- -------- -------- -------- 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 NEM S.D. N 10.0 .34 6 9.9 .22 9.6 .48 6 10.2 .60 6 6.0 .36 6 4.6 * .30 5.1 * .51 6 5.0 * .30 6 162 6.5 6 160 2.9 4 160 3.6 6 161 3.5 6 5.8 .59 6 5.2 .43 4 5.5 .60 6 5.8 .67 6 120 5.1 6 120 2.2 4 123 3.0 6 120 1.8 6 149 Table 24 summary of Clinical Chemistry Data Hales Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH BERFLUOROOCTANE SULFMIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL -------- -------- -------- ------- AL13 G/DL -------- GLOB G/DL T HILI NO/DL SBA UMOL/L CHOL NO/DL ------- -------- -------- -------- 0 MEAN 60 20 1.1 8.7 4.8 3.9 .7 S.D. 8.0 4.3 .14 .40 .12 .33 .38 N 6 6 6 6 6 6 6 8 154 1.2 24.6 6 6 0.03 MEAN 64 204.9 1..322 9..698 5..339 4..275 ..143 7.6 4 4 4 4 4 S.D. N 4 4 a 126 .6 14. 4 4 0.15 MEAN 75 19 1.2 9.0 5.0 4.0 .4 19.5. 4.6 .16 .19 .14 .21 .22 S.D. N 6 6 6 6 .6 6 6 9 150 2.7 Is. 6 6 0.75 73 19 1.4 9.4 5.2 4.2 .3 10 112 MEAN S.D. 19.1 1.3 .19 .36 6 .31 6 .35 6 .05 6 3.6 27. 6 6 N 6 6 6 150 Table 24 summary of Clinical Chemistry Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ AST/SGOT ALT/SGPT ALK PHOS GGT SDH IU/L CK IU/L AKYLASE IU/L LIPASE IU/L P AN U/ ---I-U-/L-- ---I-U/-L------I-U-/L--- ---I-U-/L--- -------- -------- -------- -------- 0 MEAN S.D. N 39 7.7 6 35 15.8 6 866 296.2 6 136 50.1 6 7 168 392 2.6 32.4 111.8 6 6 6 33 30.3 6 0.03 MEAN S.D. N 35 7.0 4 60 55.8 4 789 401.7 4 131 34.5 4 4 175 465 1.4 42.5 185.6 4 4 4 48 57.9 4 0.15 MEAN 42 45 851 140 S.D. 12.2 22.4 265.3 58.6 N- 6 6 6 6 6 164 377 4.3 36.2 94.9 6 6 .6 27 18.3 6 0.75 MEAN S.D. N 36 6.3 6 44 21.0 6 807 428.6 6 127 27.4 6 2 214 .6 75.7 6 6 468 149.1 6 32 17.5 6 151 Table 24 summary of Clinical Chemistry Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERPLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFMIC MONKEYS ACID DOSE mg/kg/day ------ CA MG/DL -------- I PHOS MG/DL -------- MA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- 0.03 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N MEAN S.D. N 10.3 .77 6 10.5 .79 4 10.6 .51 6 10.8 .41 6 6.8 .37 6 6.7 .70 4 6.8 1.05 6 6.4 .94 6 160 7.1 6 167 4.9 4 161 4.6 6 163 5.0 6 5.1 .56 6 5.7 1.04 4 5.4 .35 6 5.4 .45 6 117 5.3 6. 120 4.1 4 lie 7.0 6 117 4.2 6 152 Table 24 Summary of Clinical Chemistry Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-629S) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ GLU MG/DL UN MG/DL CRRAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA UHOL/L CHOL MG/DL -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 66 20 1.2 9.2 4.7 4.6 .4 20.S 2.7 .10 .51 .38 sl .16 6 6 6 6 6 6 6 a 166 1.5 42.0 6 6 0.03 MEAN 68 22 1.1 9.0 4.6 4.4 .5 S.D. 14.7 3.3 .08 .69 .19 .54 .27 N 4 4 4 4 4 4 8 134 1.4 15.6 4 4 0.1s MEAN 60 20 1.0 9.1 4.4 4.6 .4 10 140 S.D. 12.4 4.2 .05 .24 .41 .32 .10 5.8 13.1 N 6 6 6 6 6 6 6 6 6 0.75 MEAN 79 22 1.2 9.5 4.9 4.7 .3 11 ill S.D. 15.5 6.3 .19 .45 .29 .33 .08 7.0 26.6 N 6 6 6 6 6 6 6 6 6 153 Table 24 Summary of Clinical Chemistry Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH @ERFLUOROOCTAME 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 ANYL U/L ------- 0 0.03 MEAN S.D. N MEAN S.D. N 44 9.1 6 43 14.6 4 54 17.9 6 79 26.6 4 329 128.7 6 233 57.5 4 110 46.5 6 103 78.3 4 6 786 370 2.2 947.2 87.4 6 6 6 4 220 390 4.4 39.4 99.8 4 4 4 15 23 17.5 6 6 is 26 10.9 6 4 0.1s 0.75 MEAN S.D. N MEAN S.D. N 37 11.1 6 34 9.8 6 67 42.8 6 45 13.0 6 324 140.3 6 388 150.1 6 74 19.2 6 63 22.3 6 4 2.5 6 2 .5 6 209 81.8 6 416 377.0 6 442 127.6 6 379 96.5 6 40 28 46.1 8 6 19 2 13.6 6 154 Table 24 summary of Clinical Chemistry Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE 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 10.2 1.11 6 5.7 .66 6 161 5.9 6 5.6 .74 6 118 6.1 6 0.03 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 10.2 1.21 4 10.0 .53 6 10.6 .58 6 4.2 .44 4 S.2 .63 6 5.1 .53 6 161 7.5 4 160 3.4 6 162 4.7 6 5.2 .93 4 5.7 .45 6 5.8 .54 6 117 6.8 4 120 4.2 6 118 3.9 6 155 Table 25 Summary of Clinical Chemistry Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTAME SULFONIC POTASSIUM SALT (PFOS: T-6295) IN CYNOMOEOGUS MONKEYS ACID DOSE mg/kg/day ------ GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALS G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA UNOL/L -------- CHOL MG/DL -------- TRI MG/ ----- 0 MEAN S.D. N 60 8.0 6 20 3.0 6 1.1 .12 6 8.2 .45 6 4.8 .19 6 3.4 .34 6 .7 10 154 .41 1.5 29.9 6 6 6 0.03 MEAN 61 19 1.2 8.8 5.2 3.6 .4 S.D. 4.3 2.2 .19 .83- .24 .66 .08 N 4 4 4 4 4 4 A 7 120 1.0 16.3 4 4 0.15 um S.D. N 63 22 1.2 8.8 5.0 3.8 .5 10 149 9.4 4.5 .18 .55 .31 .61 .20 2.3 22.8 6 6 6 6 6 6 6 6 6 0.75 MEAN S.D. N 76 17.0 6 20 2.2 6 1.3 .20 6 9.0 .23 6 4.9 .48 6 4.1 .43 6 .2 14 6S .05 5.S 20.3 6 6 6 156 Table 25 Summary of Clinical Chemistry Data Hales Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME 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 -------- ANYLASE IU/L -------- LIPASE IU/L -------- P AM U/L ------ 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 31 4.9 6 30 6.3 4 40 15.7 6 39 8.8 6 43 27.3 6 36 19.8 4 55 17.2 6 52 26.6 6 792 305.3 6 684 348.2 4 853 207.5 6 646 384.1 6 142 53.1 6 123 32.2 4 149 63.8 6 112 36.1 6 3 165 392 2.6 28.5 112.8 6 6 6 23 2 10.5 6 2 133 470 1.5 42.6 165.2 4 4 4 41 3 40.0 1 4 193 429 166 3 3.1 38.4 69.9 339.9 6 6 6 6 2 352 1.2 297.5 6 6 517 124.S 6 32 17.2 6 157 Table 25 Summary of Clinical Chemistry Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH @ERFLUOROOCTANE POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ CA MG/DL -------- I PHOS MG/DL MA MMOL/L -- ----- ----- -- K MMOL/L CL MMOL/L -------- -------- 0 0.03 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N MEAN S.D. N 10.1 .73 6 10.8 .56 4 10.4 .64 6 10.8 .76 6 6.6 .31 6 6.3 1.09 4 6.8 1.01 6 6.8 1.66 6 157 6.1 6 159 3.9 4 158 3.2 6 Ise 7.9 6 5.4 .48 6 5.5 .67 4 5.5 .43 6 5.8 .73 6 116 4.1 6 117 4.1 4 115 4.2 6 113 7.8 6 158 Table 25 Summary of Clinical Chemistry Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS SULFONIC 14ONKEYS 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 UNOL/L CHOL MG/DL TRIG MG/D -------- -------- -------- -------- -------- -------- -------- -------- -- ----- ----- 0 MEAN 58 20 1.1 8.9 4.7 4.2 .5 .S.D. 9.9 4.0 .14 .80 .47 .63 .27 N 6 6 6 6 6 6 6 9 163 13 48.5 6* 6 0.03 MEAN 64 20 1.1 8.6 4.4 4.2 .5 S.D. 12.1 6.0 .17 .25 .40 .29 .34 N 4 4 4 4 4 & 4 8 110 1.7 22.1 4 4 0.15 MEAN 57 22 1.1 8.8 4.5 4.2 .5 10 130 S.D. 4.9 3.1 .08 .33 .37 .48 .12 3.1 23.2 N 6 6 6 6 6 6 6 6 6 0.75 MEAN 70 is 1.2 8.9 4.5 4.4 .3 15 91 S.D. 14.6 5.3 .14 .43 .41 .40 .09 13.8 23.1 N 6 6 6 6 6 6 6 6 6 159 Table 25 Summary of Clinical Chemistry Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH @BRFLUOROOCTANE 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 -------- cx IU/L -------- ANYLASE IU/L -------- LIPASS IU/L -------- P AMYL U/L ------- 0 0.03 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N MEAN S.D. N 36 0.2 6 38 16.2 4 36 13.4 6 40 6 77 43.3 6 00 52.8 4 66 34.1 6 48 10.0 6 315 143.3 6 262 42.2 4 309 120.9 6 336 146.9 6 112 51.2 6 108 97.8 4 72 20.3 6 61 24.2 6 2 .8 6 2 .8 4 3 2.5 6 2 2.3 6 235 105.0 6 255 131.7 4 242 116.5 6 695 1217.1 6 373 74.3 6 378 108.8 4 432 165.5 6 380 104.1 6 is 25 17.7 5 5 is 27 13.5 6 4 25 29 15.2 12 6 26 28 10.9 7 6 160 Table 25 Summary of Clinical Chemistry Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE P(YRASSIUN SALT (PFOS; T-6295) IN CYNONOLGUS SULFONIC NOMMS ACID DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L -------- -- ----- ------- K MMOL/L CL MMOL/L -------- -------- 0 0.03 0.15 MEAN S.D. N MEAN S.D. N MEAN S.D. N 10.2 .87 6 9.8 1.04 4 9.8 .42 6 5.6 .34 6 4.1 .84 4 5.0 .96 6 158 8.5 6 iss 6.9 4 154 2.2 6 6.0 .81 6 5.6 .46 4 5.4 .52 6 119 7.2 6 116 6.9 4 116 3.6 6 0.75 MEAN S.D. N 10.5 .67 6 4.9 .71 6 158 5.0 6 6.3 .75 6 116 4.4 6 161 Table 26 Summary of Clinical Chemistry Data males Day 182 26-WEEX CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB GLOB T BILI SBA CHOL TRI G/DL G/DL MG/DL UNOL/L MG/DL MG/ -------- -------- -------- -------- -------- -------- -------- -------- -------- ----- 0 MEAN S.D. N 60 le 1.1 8.2 4.8 3.5 .6 6.1 3.9 .16 .54 .23 .40 .23 6 6 6 6 6 6 6 6 152 .8 27.5 6 6 0.03 MEAN 64 le 1.2 8.8 5.0 3.8 .3 S.D. 9.1 6.3 .16 .65 .34 .47 .08 N 4 4 4 4 4 4 4 5 110 .5 17.0 4 4 0.15 MEAN 70 17 1.1 8.5 4.9 3.6 .4 S.D. 8.3 2.6 .17 .30 .31 .17 .10 N 6 6 6 6 6 6 6 6 147 1.3 24.0 6 6 0.75 MEAN 76 22 1.2 9.0 4.9 4.1 .2 le 48 4.5 .24 .77 .53 .44 .05 4 4 4 4 8.6 18.8 4 4 S.D. 12.6 N 4 4 4 162 Table 26 summary of Clinical Chemistry Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AKYLRSE IU/L LIPASE IU/L P ANYI . U/L -------- -------- -------- -------- -------- -------- -------- -------- ------- 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 32 6.2 6 27 6.2 4 36 13.3 6 34 5.3 4 39 17.9 6 29 8.8 4 47 16.9 6 47 19.7 4 735 318.7 6 604 353.5 4 689 178.3 6 389 155.7 4 150 65.6 6 126 42.6 4 149 55.8 6 104 25.3 4 6 210 393 3.7 158.7 102.8 6 6 6 4 138 442 1.9 58.8 136.5 4 4 4 6 174 381 3.8 101.5 82.3 6 6 6 3 182 1.0 64.5 4 4 446 65.3 4 29 2 13.4 6 24 3 10.6 4 30 2 11.0 6 36 3 22.2 4 163 Table 26 summary of clinical chemistry Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNONOTGUS SULPONIC MONKEYS ACID DOSE mg/kg/day ------ CA MG/DL -------- I PHOS MG/Dt. ---- --- uh MMOL/L x KNOL/L CL Mt4OL/L -------- -------- -------- 0 0.03 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N MEAN S.D. N 10.2 .43 6 10.0 .20 4 10.1 .41 6 10.3 .62 4 6.4 .82 6 5.8 .96 4 6.2 .82 6 6.1 1.22 4 154 4.8 6 156 1.5 4 154 4.7 6 153 6.4 4 5.1 .23 6 5.0 .32 4 5.0 .25 6 5.4 .17 4 ill 1.5 6 109 2.2 A 110 2.9 6 106 5.3 4 164 Table 26 summary of clinical Chemistry Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS; T-6295) IN CYNONOT.GUS 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 UNOL/L CHOL MG/DL TRIG MG/D -------- -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN 58 20 1.1 8.9 4.7 4.2 .4 S.D. 15.2 3.7 .18 .66 .42 .55 .25 N 6 6 6 6 6 6 6 0.03 MEAN 54 20 1.0 8.6 4.4 4.2 .5 S.D. 7.8 3.4 .17 .76 .47 .38 .24 N 4 4 4 4 4 4 4 0.15 MEAN 64 19 1.0 8.9 4.5 4.4 .4 S.D. 9.0 3.1 .09 .47 .35 .67 .09 N 6 6 6 6 6 6 6 0.75 MEAN 73 20 1.2 9.2 4.6 4.7 .2 S.D. 11.0 4.7 .16 .37 .31 .63 .08 N 6 6 6 6 6 6 6 6 160 .6 46.5 6 6 5 122 1.5 21.6 4 4 8 129 2.0 22.3 6 6 7 82 3.4 14.7 6 6 165 Table 26 Summary of Clinical Chemistry Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SMFOUIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L cx ZU/L ANYLASE IU/L LIPASE IU/L p AM U/L -------- -------- -------- --- ---- -------- -------- -------- -------- ------ 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 41 25.0 6 42 14.6 4 37 13.0 6 33 6.2 6 87 85.9 6 72 26.3 4 53 36.1 6 44 9.9 6 283 137.1 6 239 39.7 4 254 85.3 6 316 172.4 6 114 53.3 6 ill 99.5 4 71 19.7 6 64 22.7 6 5 212 3.1 123.4 6 6 6 823 6.0 1281.8 4 4 7 182 5.2 84.7 6 6 3 284 1.5 119.3 6 6 378 84.6 6 358 100.7 4 439 140.9 6 375 64.9 6 32 2 37.1 6 19 2 15.0 4 33 2 21.6 1 6 31 2 21.2 6 166 Table 26 summary of Clinical Chemistry Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE 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 tML/L CL MIOL/L -------- -------- -------- -------- -------- 0 0.03 0.15 0.75 MEAN S.D. N ME" S.D. N MEAN S.D. N KEAN S.D. N 10.2 .68 6 9.6 .84 4 9.8 .16 6 10.3 .69 6 5.3 .84 6 4.4 .39 4 4.8 1.10 6 5.2 .76 6 156 6.8 6 152 7.2 4 154 3.3 6 ls6 4.9 6 5.3 .56 6 4.8 .94 4 5.0 .37 6 5.4 .82 6 ill 5.0 6 109 3.6 4 110 1.8 6 110 3.1 6 167 26-WEEK Table 27 Summary of Clinical Chemistry Data Males Day 217 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULPONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID DOSE m-g-/-k-g-/-day GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO O/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI 14G/DL -------- sRh UNOL/L -------- CHOL MG/DL -------- TRI MG/ ----- 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 57 2.8 .2 70 12.0 2 73 4.2 2 16 4.9 2 17 .0 2 14 2.1 2 1.0 .07 2 .9 .14 2 1.0 .07 2 8.0 .21 2 9.0 .42 2 0.7 .00 2 4.6 .07 2 5.1 .00 2 4.6 .35 2 3.4 .14 2 3.9 .42 2 4.2 .35 2 .5 12 132 .14 1.4 28.3 2 2 2 .6 16 158 .21 .0 37.5 2 2 2 .6 14 137 .00 3.5 4.2 2 2 2 168 26-WEEK Table 27 summary of Clinical Chemistry Data males Day 217 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT JPFOS; T-6295) IN CYNOMOLOUS ACID DOSE mg/kg/day ------ AST/SGOT IU/L ------- ALT/SGPT ALK PHOS IU/L IU/L GGT IU/L SDH iu/L CK IU/L ANYLASE IU/L LIPASE IU/L p AN U/ -------- ---------------- -------- -------- ---------------- ----- 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 22 3.5 2 37 8.5 2 32 4,9 2 26 3.5 2 44 2.1 2 48 28.3 2 932 316.1 2 793 175.4 2 518 27.6 2 150 123.7 2 138 68.6 2 143 22.6 2 4 .7 2 12 1.4 2 2 .7 2 139 77.8 2 162 21.9 2 200 32.5 2 338 87.7 2 454 42.4 2 505 53.7 2 36 7.8 2 46 2.1 2 38 21.2 2 169 26-WEEK Table 27 Summary of Clinical Chemistry Data Males Day 217 CAPSULE TOXXCITY STUDY WITH PERFLUOROOCTANE SULFCNIC PoTAssium SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ CA MG/DL -------- X PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 10.0 .57 2 11.0 .78 2 10.8 .21 2 6.3 1.13 2 6.6 .00 2 6.2 1.13 2 152 2.8 2 155 1.4 2 159 2.8 2 5.0 .49 2 5.3 .28 2 5.4 .07 2 ill 1.4 2 108 2.8 2 ill 1.4 2 170 26-WEEK Table 27 Summary of Clinical Chemistry Data Females Day 217 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 NO/D ------ 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 59 16 .8 8.6 4.6 4.0 .4 14 119 .42 1.4 46.7 11.3 4.9 .14 .242 .221 .22 1 2 2 2 2 2 2 76 is 1.0 8.7 4.0 4.6 .21 .6 .00 14 .7 145 4.2 .7 2.1 .00 .14 .07 2 2 2 2 2 2 2 2 2 75 23 1.0 9.3 4.6 4.7 .6 19 133 .07 7.1 2.8 92.9 22 .8 .221 .242 .257 .214 2 2 2 171 26-WEEK Table 27 Summary of Clinical Chemistry Data Females Day 217 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day - ------ AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AHMSE IU/L LIPASE IU/L P AM U/L -------- -------- -------- -------- -------- -------- ------;-- -------- ------ 0. MEAN S.D. N 34 .7 2 103 24.0 2 184 33.2 2 61 28.3 2 4 137 .7 28.3 2 2 343 48.1 2 13 2 18.4 2 0.15 MEAN S.D. N 26 9.9 2 48 7.8 2 182 97.6 2 70 2.1 2 4 657 486 4.2 763.7 244.0 2 2 2 32 21.9 2 0.75 MEAN S.D. N 23 .0 2 50 16.3 2 220 29.0 2 94 37.5 2 4 165 345 2.1 29.7 69.3 2 2 2 38 4.2 2 172 26-WEEK Table 27 Summary of Clinical Chemistry Data Females Day 217 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID DOSE .mg/kg/day ------ CA 14G/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL NHOL/L -------- 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 9.8 .14 2 9.8 .14 2 10.3 .14 2 4.8 1.56 2 5.5 .28 2 5.8 .64 2 148 4.9 2 152 3.5 2 152 0 2 5.4 .64 2 5.5 .00 2 5.0 .21 2 108 6.4 2 110 2.1 2 110 2.1 2 173 26-WEEK Table 28 Summary of Clinical Chemistry Data Males Day 245 CAPSULE TOXICITY STUDY WITH @ERFLUOROOCTME SULPONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE m-g-/-k-g/-d-ay GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL GLOB G/DL -------- -------- T BILI MG/DL -------- sBh UNOL/L -------- CHOL MG/DL -------- TitiG MG/ ------ 0 MEAN 101 16 1.1 8.7 4.8 3.8 .4 S.D. 21.2 1.4 .14 .14 .07 .07 .07 N 2 2 2 2 2 2 2 8 .7 2 134 29.0 2 0.15 MEAN 81 17 1.1 9.0 5.2 3.8 .6 S.D. 2.8 .0 .14 .14 .07 .07 .28 N 2 2 2 2 2 2 2 9 160 4.2 46.0 2 2 0.75 MEAN 72 17 1.0 8.8 4.6 4.2 .4 11 136 S.D. 16.3 1.4 .00 .35 .35 .00 .00 N 2 2 2 2 2 2 2 5.7 4.9 2 2 174 26-WEEK Table 28 Summary of Clinical Chemistry Data males Day 245 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULFONIC POTASSIUM SALT 4PPOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ AST/SGOT ALT/SGPT ALK PHOS ZU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L ANYLASE IU/L LIPASE IU/L p AN U/ -------- -------- -------- -------- -------- -------- -------- -------- ----- 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 27 4.2 2 34 21.2 2 46 4.9 2 28 .7 2 40 .0 2 53 28.3 2 900 334.5 2 838 62.9 2 680 78.5 2 144 107.5 2 142 62.2 2 166 14.1 4 177 358 2.8 45.3 72.1 2 2 2 4 156 462 3.5 46.0 57.3 2 2 2 4 257 544 3.5 111.7 118.9 2 2 2 42 13.4 2 37 21.2 2 32 21.9 2 175 26-WEEK Table 28 Summary of Clinical Chemistry Data Males Day 245 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTMM SULFONIC P(YRASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MML/L -------- -------- -------- -------- -------- 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.2 .35 2 10.9 .57 2 10.8 .64 2 6.6 .64 2 6.6 .21 2 7.0 1.13 2 154 3.5 2 160 7 2 162 3.5 2 5.0 .00 2 5.2 .07 2 5.2 .28 2 117 .0 2 117 1.4 2 116 2.8 2 176 26-WEEK Table 28 Summary of Clinical Chemistry Data Females Day 245 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFOWIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 UNOL/L CHOL MG/DL TRI( MG/ -------- -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN 58 18 1.0 9.0 4.6 4.4 .6 S.D. 14.1 3.5 .35 .64 .14 .49 .35 N 2 2 2 2 2 2 2 9 131 1.4 52.3 2 2 0.15 MEAN 87 20 1.0 9.0 4.1 4.9 .4 11 150 S.D. 5.7 1.4 .14 .28 .14 .14 .14 1.4 17.7 N 2 2 2 2 2 2 2 2 2 0.75 ME.AN 92 22 1.2 9.4 4.7 4.7 .2 is 149 s D. .7 .0 .07 .57 .42 .14 .07 5.7 2.8 N 2 2 2 2 2 2 2 2 2 177 26-WEEK Table 28 Summary of Clinical Chemistry Data Females Day 245 CAPSULE TOXICITY STUDY WITH @ERFLUOROOCTAWE SULFOUIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 ANY U/L ------ 0 MEAN S.D. N 36 9.2 2 116 59.4 2 182 30.4 2 58 20.5 2 2 .7 2 168 50.9 2 329 48.1 2 10 2 14.8 2 0.15 0.75 MEAN S.D. N MEAN S.D. N 30 9.2 2 25 4.2 2 66 7.1 2 40 1.4 2 188 105.4 2 236 17.7 2 so 4.2 2 98 33.2 2 3 2.8 2 2 .7 2 392 384.0 2 148 27.6 2 482 242.5 2 331 76.4 2 34 3 17.7 1 2 66 2 66.5 2 178 Table 28 Summary of Clinical Chemistry Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTAM SULFONIC ACID POTASSIUM SALT IPFOS; T-6295) IN CYNONOEGUS DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL NHOL/L -------- -------- -------- -------- -------- 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 9.7 .14 2 9.0 .49 2 10.6 .57 2 4.6 .28 2 5.4 .28 2 5.4 .71 2 150 4.2 2 152 4.9 2 160 7.8 2 4.6 .21 2 5.4 .71 2 5.5 .99 2 114 4.9 2 lie 2.1 2 120 6.4 2 179 26-WEEK Table 29 Summary of Clinical Chemistry Data males Day 274 CAPSULE TOXICITY STUDY WITH @ERFLUOROOCTANE SULFMIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day OLU MG/DL UN MG/DL CREAT HG/DL T PRO G/DL ALS GLOB T BILI SBA CHOR. TRI G/DL G/DL MG/DL UMOL/L MG/DL MG/ ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 67 16 1.2 8.5 4.7 3.8 .4 S.D. 18.4 3.5 .14 .42 .14 .28 .42 N 2 2 2 2 2 2 2 0.15 MEAN 74 19 1.0 8.8 5.0 3.8 .4 S.D. 2.8 1.4 .14 .21 .21 .00 .14 N 2 2 2 2 2 2 2 0.75 MEAN 70 is 1.2 8.8 4.8 4.0 .3 S.D. 9.2 3.5 .21 .07 .42 .35 .14 N 2 2 2 2 2 2 2 2 130 .7 26.2 2 2 9 168 2.8 50.2 2 2 a 139 3.5 5.7 2 2 180 26-WEEK Table 29 summary of Clinical Chemistry Data males Day 274 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L ANYLASE IU/L LIPASE IU/L P ANY U/L -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 28 12.7 2 26 6.4 2 38 3.5 2 35 5.7 2 39 4.2 2 54 21.2 2 842 409.4 2 850 105.4 2 689 186.7 2 124 90.5 2 146 70.0 2 164 7.8 2 7 176 318 4.2 35.4 71.4 2 2 2 4 141 444 2.8 22.6 43.1 2 2 2 4 230 .7 89.8 2 2 512 84.1 2 36 2 7.1 2 39 2 2.8 2 35 3 24.0 2 181 26-WEEK Table 29 Summary of clinical Chemistry Data Males Day 274 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNO14OLGUS ACID DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L K KHOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.2 .21 2 11.2 1.20 2 11.2 .57 2 6.0 1.13 2 6.4 .21 2 6.4 .92 2 154 4.9 2 159 7.1 2 160 3.5 2 5.8 .21 2 5.6 .35 2 5.6 .35 2 116 .7 2 lie 6.4 2 114 2.1 2 182 26-WEEK Table 29 summary of clinical Chemistry Data Females Day 274 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 UNOL/L -------- CHOL MG/DL -------- TRIG MG/Dt ------- 0 MEAN 56 20 .8 8.7 4.4 4..357 ..567 S.D. 15.6 4.9 .200 .285 .228 2 2 N 2 2 0.15 MEAN 71 21 ..194 8..928 4..000 4..928 ..421 S.D. N 4.9 2.8 2 2 2 2 2 2 2 0.75 MEAN 92 23 1.0 9.0 4.4 4.6 .1 S.D. N 3.5 4.2 .14 .35 .42 .07 .00 2 2 2 2 2 2 2 9 2.1 2 5 .0 2 6 2.1 2 129 58.0 2 144 6.4 2 144 .7 2 183 26-WEEK Table 29 Summary of Clinical Chemistry Data Females Day 274 CAPSULE TOXICITY STUDY WITH IERPLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day AST/SGOT IU/L ------ - ALT/SGPT IU/L ALK PHOS ZU/L GGT IU/L SDH IU/L CK IU/L ANYLASE IU/L LIPASE ZU/L p AN U/ -------- -------- -------- -------- -------- -------- -------- ----- 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 40 9.9 2 37 14.1 2 29 18.4 2 104 34.6 2 58 2.1 2 44 10.6 2 163 35.4 2 172 94.0 2 226 25.5 2 58 17.7 2 76 .7 2 87 29.7 2 3 301 1.4 199.5 2 2 9 1214 7.1 1557.8 2 2 5 142 1.4 31.8 2 2 309 26.9 2 468 256.0 2 316 113.9 2 9 12.7 2 74 33.9 2 32 2.1 2 184 26-WEEK Table 29 Summary of clinical Chemistry Data Females Day 274 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA IML/L x MOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 MEAN S.D. N 9.8 .78 2 4.4 .28 2 150 7.8 2 5.0 .92 2 110 4.9 2 0.15 0.7S MEAN S.D. N MEAN S.D. N 9.5 .00 2 10.4 .00 2 5.2 .07 2 5.2 .85 2 150 2.8 2 156 2.1 2 4.8 .92 2 6.0 .07 2 ill 5.7 2 119 2.8 2 185 26-WEEK Table 30 summary of Clinical Chemistry Data Males Day 322 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTAME SULFONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ GLU MG/DL um MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB O/DL T BILI MG/DL SBA UMOL/L CHOL MG/DL TRIG MG/D -------- -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN 71 le 1.2 8.6 4.0 3.8 .4 S.D. 4.2 2.1 .07 .07 .14 .07 .57 N 2 2 2 2 2 2 2 6 134 .7 34.6 2 2 0.15 MEAN 62 28 1.4 8.7 5.1 3.6 .7 S.D. 23.3 2.8 .21 .42 .14 .28 .71 N 2 2 2 2 2 2 2 0.75 MEAN 66 le 1.4 8.6 4.7 38 .4 S.D. 14.8 .7 .35 .49 .42 :07 .28 N 2 2 2 2 2 2 2 7 163 1.4 65.1 2 2 8 136 2.1 .7 2 2 186 26-WEEK Table 30 Summary of Clinical Chemistry Data Males Day 322 CAPSULE TOXICITY STUDY WITH OERFLUOROOCTME SULPONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ AST/SGOT IU/L ALT/SGPT IU/L -------- -------- ALK PHOS IU/L -------- OGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P ANY U/L ------ 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 38 5.7 2 53 9.9 2 61 21.2 2 38 6.4 2 68 7.1 2 76 23.3 2 772 386.8 2 882 159.1 2 708 191.6 2 124 105.4 2 140 68.6 2 157 1.4 2 4 966 1.4 149.2 2 2 497 35.4 2 94 3 5.7 2 6 570 1297 710 9 .0 77.1 454.0 227.7 3 2 2 2 2 2 1048. 1.4 368.4 2 2 625 144.2 2 30 4 7.8 2 187 26-WEEK Table 30 Summary of Clinical Chemistry Data males Day 322 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIU14 SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ CA MG/DL -------- I PHOS MG/DL -------- MA MMOL/L -------- K MMOL/L -------- CL MML/L ------ 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 10.4 .49 2 11.0 .92 2 10.6 .92 2 5.4 .57 2 5.8 .64 2 5.8 1.13 2 150 3.5 2 154 .0 2 154 4.9 2 5.0 .14 2 5.0 .07 2 5.4 .35 2 106 .7 2 106 2.8 2 108 .0 2 188 26-WEEK Table 30 Summary of Clinical Chemistry Data Females Day 322 CAPSULE TOXICITY STUDY WITH @ERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ CLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA UNOL/L -------- CHOL MG/DL -------- TRI NGI ----- 0 MEAN S.D. N 54 14.1 2 15 1.4 2 1.2 .21 2 8.4 .07 2 4.4 .07 2 4.1 .14 2 .5 10 118 .57 4.9 41.7 2 2 2 0.15 MEAN 64 28 1.3 8.8 3.9 4.8 .5 S.D.. 7.8 .7 .14 .78 .14 .64 .00 N 2 2 2 2 2 2 2 a 148 3.5 9.2 2 2 0.75 MEAN es is 1.5 8.7 4.3 4.4 S.D. 1.4 9.2 .14 .64 .42 .21 .07 N 2 2 2 2 2 2 2 6 129 2.1 14.1 2 2 189 26-WEEK Table 30 Summary of Clinical Chemistry Data Females Day 322 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ AST/SGOT ALT/SGPT ALK PHOS IUIL IU/L IU/L GGT IU/L SDH iu/L CK ANYLASE LIPASE pm IU/L IU/L IU/L u -------- -------- -------- -------- -------- -------- -------- -------- ---- 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 56 14.1 2 48 17.0 2 44 2.1 2 87 14.1 2 78 9.9 2 112 60.1 2 156 18.4 2 160 64.3 2 235 21.2 2 60 30.4 2 73 8.5 2 80 35.4 2 4 ilia 2.1 132.9 2 2 6 1058 3.5 644.2 2 2 2 1065 .7 574.2 2 2 366 33.9 2 554 237.6 2 449 1.4 2 0 .0 2 73 14.1 2 64 43.1 2 190 Table 30 Summary of Clinical Chemistry Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLTIOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYROMOLGUS DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L x MMOL/L CL NML/L -------- -------- -------- -------- -------- 0 MEAN S.D. N 9.7 .14 2 4.7 .42 2 147 1.4 2 5.0 .21 2 104 4.9 2 0.15 0.75 MEAN S.D. N MEAN S.D. N 9.8 .57 2 10.3 .00 2 5.2 .49 2 4.2 .21 2 151 4.2 2 156 2.8 2 5.2 .07 2 5.5 .42 2 108 1.4 2 110 1.4 2 191 26-WEEK Table 31 Summary of Clinical Chemistry Data males Day 364 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOMIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALS G/DL GLOB G/DL T BILI MG/DL SBA UNOL/L CHOL MG/DL TRIG MG/DL -------- -------- -------- -------- -------- -------- -------- -------- -------- ------- 0 MEAN 72 20 1.3 8.9 5.2 3.8 .5 S.D. 2.1 4.9 .00 .00 .21 .21 .28 m 2 2 2 2 2 2 2 6 126 4 .7 30.4 2 2 0.15 MEAN 74 26 1.2 8.6 5.2 3.4 .8 S.D. 2.1 3.5 .07 .64 .35 .28 .42 N 2 2 2 2 2 2 2 0.75 MEAN 70 18 1.2 8.4 4.8 3.6 .4 S.D. 9.2 1.4 .14 .14 .35 .21 .21 N 2 2 2 2 2 2 2 6 166 4 .7 55.9 2 2 2 4 119 5 2.1 4.2 2 2 2 192 26-WERX Table 31 Summary of Clinical Chemistry Data Kales Day 364 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULPONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L cx IU/L AMYLASE IU/L LIPASE IU/L P AKYL U/L -------- -------- -------- -------- -------- -------- -------- -------- ------- 0 0.15 0.75 KEAN S.D. N MEAN S.D. N MEAN S.D. N so 4.9 2 60 6.4 2 60 2.8 2 42 4.9 2 66 4.9 2 66 25.5 2 714 461.7 2 820 134.4 2 622 202.2 2 138 119.5 2 143 63.6 2 155 1.4 2 6 2137 3.5 19.8 2 2 376 17.7 2 38 27 .7 3 2 8 1495 1294 579 95 .7 356.4 489.3 302.6 35 2 2 2 2 4 1310 2.8 980.8 2 2 516 242.1 2 33 35 2.8 7 2 193 26-WEEK Table 31 Summary of Clinical Chemistry Data males Day 364 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOUIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA Mt4OL/L x MMOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 MEAN 10.6 S.D. .49 N 2 4.7 .71 2 156 2.1 2 5.4 .14 2 ill .0 2 0.15 MEAN S.D. N 10.9 1.41 2 5.6 .14 2 iss 7.1 2 5.4 .49 2 ill 2.8 2 0.75 MEAN S.D. N 10.6 .49 2 4.9 .42 2 154 2.1 2 5.4 .64 2 110 3.5 2 194 26-WEEK Table 31 summary of Clinical Chemistry Data Females Day 364 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 SEA UNOL/L CHOL MG/DL TRIG @NG/D -------- -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN 55 20 1.0 9.0 4.7 4.2 .8 S.D. 1.4 2.1 .14 .07 .00 .07 .49 N 2 2 2 2 2 2 2 6 137 .7 35.4 2 2 0.15 ME.AN 73 24 1.0 8.7 3.9 4.8 .8 s D. 9.9 2.8 .07 .57 .14 .42 .07 N 2 2 2 2 2 2 2 6 137 .0 1.4 2 2 0.75 ME.AN 88 23 1.2 8.7 4.4 4.2 .4 -S D. 4.2 2.8 .07 .79 .64 .14 .07 N 2 2 2 2 2 2 2 9 142 5.7 14.8 2 2 195 Table 31 Summary of Clinical chemistry Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLTIOROOCTAWE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS DOSE mg/kg/day ------ AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L cx IU/L ANYLASS IU/L LIPASE IU/L P AN U/ -------- -------- -------- -------- -------- -------- -------- -------- ----- 0 MEAN S.D. N 0.15 KHAN S.D. N 0.75 MEAN S.D. N 86 34.6 2 50 17.7 2 56 15.6 2 202 135.1 2 78 24.0 2 00 3.5 2 162 7.1 2 148 55.9 2 228 21.2 2 77 45.3 2 79 1.4 2 06 43.1 2 .6 1.4 2 12 4.9 2 4 1.4 2 2408 806.1 2 871 195.2 2 1797 786.3 2 396 85.6 2 467 230.5 2 479 67.9 2 16 23.3 2 47 7.1 2 47 .0 2 196 26-WEEK Table 31 Summary of Clinical Chemistry Data Females Day 364 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ CA NG/DL -------- I PHOS MG/DL NA MMOL/L K MHOL/L CL MML/L ------ -------- -------- -------- 0 MEAN S.D. N 9.9 .28 2 4.9 .99 2 148 4.9 2 5.0 .92 2 106 4.2 2 0.15 MEAN S.D. N 9.4 .64 2 4.8 .07 2 148 3.5 2 5.4 .71 2 110 2.1 2 0.75 MEAN S.D. N 10.2 .35 2 4.4 .21 2 155 2.8 2 5.4 .21 2 112 1.4 2 197 26-WEEK Table 32 Summary of Clinical Chemistry Data males Day 456 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC POTASSIUM SALT (PPOSI T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ GLU UN CREAT T PRO ALB GLA)B T BILI SBA CHOL TRI MG/DL MG/DL MG/DL G/DL G/DL G/DL MG/DL UNOL/L MG/DL MG/ -------- -------- -------- -------- -------- -------- -------- -------- -------- ----- 0 MP" 74 14 1.2 8.7 5.0 3.6 .6 S.D. 8.5 2.8 .00 .28 .21 .07 .35 N .2 2 2 2 2 2 2 0.15 MEAN 91 16 1.2 9.1 5.4 3.6 .4 S.D. 4.2 1.4 .07 .28 .07 .35 .21 N 2 2 2 2 2 2 2 0.75 MEAN 70 14 1.2 8.9 5.0 4.0 .6 S.D. 7.8 .7 .21 .57 .64 .07 .35 N 2 2 2 2 2 2 2 3 132 .0 14.1 2 2 6 178 .7 54.4 2 2 4 118 .7 5.7 2 2 198 26-WEEK Table 32 Summary of Clinical Chemistry Data Males Day 456 CAPSIULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 AWILASS IU/L LIPASE IU/L. P ANYL U/L -------- -------- -------- -------- ------- 0 0.15 MEAN S.D. N HFJW S.D. N 24 7.1 2 25 5.7 2 24 3.5 2 46 .7 2 620 320.3 2 871 141.4 2 124 91.9 2 150 68.6 2 6 102 5.7 34.6 2 2 2 141 .7 31.1 2 2 298 30.4 2 450 52.3 2 16 23 7.1 1 2 16 29 2.1 8 2 0.75 MEAN S.D. N 34 4.9 2 41 12.7 2 418 55.9 2 138 13.4 2 0 .7 2 202 32.5 2 422 82.0 2 16 29 4.9 4 2 199 26-WEEK Table 32 summary of Clinical Chemistry Data Males Day 456 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLOUS ACID DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MMOL/L x MMOL/L CL MMOL/L -------- -- ----- ---------------- -------- 0 O.IS 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 10.2 .21 2 11.8 1.20 2 10.6 .78 2 6.0 .49 2 6.9 .42 2 5.3 1.98 2 153 4.2 2 164 4.2 2 155 4.2 2 5.4 .42 2 6.0 .49 2 5.0 .57 2 ill 2.8 2 116 3.5 2 ill 2.8 2 200 26-WEEK Table 32 Summary of Clinical Chemistry Data Females Day 456 CAPSULE TOXICITY STUDY WITH IERFLUOROOCTAN.E SUE.P@MIC ACID POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS DIOSE mg/kg/day ------ GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALS GLOB T BILI SBA CHOL TRI G/DL G/DL MG/DL UNOL/L MG/DL NGI -------- -------- -------- -------- -------- -------- -------- -------- -------- ----- 0 MEAN 64 17 1.0 8.5 4.6 3.9 .6 S.D. 21.9 .0 .07 .26 .00 .28 .49 N 2 2 2 2 2 2 2 0.15 MEAN 78 17 1.0 8.7 4.1 4.6 .6 S.D. .7 1.4 .07 .42 .00 .42 .07 N 2 2 2 2 2 2 2 0.75 MEAN 100 19 1.0 8.7 4.5 4.2 .2 S.D. 2.1 2.8 .07 .64 .57 .07 .07 N 2 2 2 2 2 2 2 6 120 2.1 30.4 2 2 5 144 1.4 .0 2 2 4 138 1.4 1.4 2 2 201 Table 32 Summary of Clinical Chemistry Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWE SULPONIC ACID POTASSIUW SALT (PFOS; T-6295) IN CYNOMOLGUS DOSE mg/kg/day ------ AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L ZU/L GGT IU/L SDH IU/L cx IU/L ANYLASE ZU/L LIPASE IU/L P ANY U/L -------- -------- -------- -------- -------- -------- -------- -------- ------ 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 43 18.4 2 32 10.6 2 25 .0 2 134 69.3 2 so 22.6 2 54 14.8 2 156 24.7 2 140 65.1 2 232 22.6 2 72 33.2 2 78 3.5 2 94 43.1 2 4 222 268 2.1 31.1 34.6 2 2 2 7 183 339 4.2 100.4 137.2 2 2 2 2 124 296 2.1 14.1 89.8 2 2 2 10 2 2.1 2 13 2 2.8 2 le 2 7.1 2 202 Table 32 summary of Clinical Chemistry Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH @ERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS DOSE mg/kg/day ------ CA MG/DL I PHOS MG/DL NA MHOL/L x MMOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 0.15 MEAN S.D. N MEAN S.D. N 9.9 .42 2 9.0 .42 2 5.2 .35 2 5.2 .21 2 148 5.7 2 152 1.4 2 5.0 .14 2 5.6 .35 2 108 3.5 2 112 .7 2 0.79 MEAN S.D. N 10.4 .14 2 5.4 .35 2 154 .7 2 6.2 .85 2 116 2.8 2 203 26-WEEK Table 33 summary of Clinical Chemistry Data males Day 546 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLOGUS 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 HILI MG/DL SBA UNOL/L CHOL M(;/DL TRIG NO/Dl -------- -------- -------- -------- -------- -------- -------- ------ 0 MEAN 82 16 1.2 8.8 4..714 4..100 ..421 S.D. 4.9 2.8 .07 .14 2 2 2 2 2 2 N 2 0.15 MEAN 79 19 1..207 8..828 5..128 3..700 ..241 .0 2 2 2 2 S.D. 2.8 N 2 2 2 0.75 MEAN 79 16 1..400 9..414 5..114 4..328 ..635 5.7 .0 2 2 2 2 2 S.D. N 2 2 6 134 .7 21.9 2 2 4 166 1.4 48.1 2 2 7 138 4.2 9.2 2 2 204 Table 33 Summary of Clinical chemistry Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTME SULPONIC ACID POTASSIUM SALT (PPOS: T-6295) IN CYNOMOLGUS DOSE mg/kg/day ------ AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AM U/L -------- ---------------- -------- -------- -------- -------- -------- ------ 0 0.15 MEAN S.D. N MEAN S.D. N 24 6.4 2 30 .7 2 25 7.1 2 34 2.1 2 505 277.2 2 754 130.1 2 116 94.8 2 136 60.1 2 10 12.7 2. 3 2.8 2 ill 46.7 2 171 58.0 2 262 4.2 2 402 62.9 2 14 2 4.9 2 12 2 .7 2 0.75 MEAN S.D. N 36 12.7 2 40 3.5 2 404 88.4 2 148 1.4 2 0 16S 440 .0 .0 111.0 2 2 2 16 7.8 2 205 26-WEEK TaLble 33 Summary of Clinical Chemistry Data Males Day 546 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ CA MG/DL -------- I PROS MG/DL -------- NA --M-M-OL-/-L - CL MMOL/L MOL/L -------- -------- 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 10.6 .21 2 11.2 .20 2 11.9 .14 2 6.6 .07 2 7.0 .92 2 5.8 .57 2 160 3.5 2 166 3.5 2 172 3.5 2 6.0 .57 2 6.4 .79 2 6.1 .14 2 116 6.4 2 120 3.5 2 lie 3.5 2 206 26-WEEK Table 33 Summary of Clinical Chemistry Data Females Day 546 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULFONIC POTASSIUM SALT (PFOS; T-6295) IN C M HOLGUS ACID DOSE mg/kg/day ------ GLU MG/DL -------- tiN MG/DL -------- CREAT T PRO ALE GLOB T BILI SBA CHOL TRIG MG/DL UMOL/L MG/DL Ma/D ..M.G./D.L... ...G./D.L... ...G./D.L... ...G./D.L... ........ ........ ........ ...... 0 MEAN 60 16 .7 1..007 8..542 4..400 4..142 ..635 2 2 S.D. N 9.9 2 2 2 2 2 6 .7 2 124 39.6 2 0.15 MEAN 72 is 1 .0 8..421 3..821 4..600 ..607 2.1 1.4 .21 2 2 2 2 S.D. N 2 2 2 0.75 MEAN S.D. N 96 19 1.2 8.4 4..342 4..235 ..300 4.9 .0 .00 .78 2 2 2 2 2 2 2 5 .0 2 5 1.4 2 1.38 12.7 2 146 1.4 2 207 26-WEEK Table 33 Summary of Clinical Chemistry Data Females Day 546 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ AST/SGOT IU/L ALT/SGPT IU/L ALK PHOS IU/L GGT IU/L SDH IU/L cx ZU/L AKYLASE IU/L LIPASE IU/L P AM U/ -------- -------- -------- -------- -------- -------- -------- -------- ----- 0 MEAN S.D. N 0.15 MEAN S.D. N .0.75 MEAN S.D. N 42 16.3 2 26 .7 2 20 12.0 2 120 100.4 2 34 4.2 2 59 28.3 2 151 28.3 2 146 70.0 2 213 38.2 2 69 33.9 2 79 4.2 2 09 39.6 2 0 154 .0 87.0 2 2 260 50.2 2 2 94 353 .7 20.5 142.8 2 2 2 2 130 311 2.1 47.4 86.3 2 2 2 12 .7 2 11 4.2 2 15 4.2 2 208 26-WEEK Table 33 Summary of Clinical Chemistry Data Females Day 546 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOSI T-6295) IN CYNO14OLGUS ACID DOSE mg/kg/day ------ Ch MG/DL I PHOS MG/DL NA KNOL/L x MMOL/L CL MMOL/L -------- -------- -------- -------- -------- 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.1 .00 2 10.0 .28 2 10.5 .28 2 5.4 .28 2 5.2 .35 2 5.6 .35 2 151 1.4 2 156 1.4 2 162 4.2 2 5.2 .14 2 5.8 .49 2 6.2 .78 2 110 2.1 2 114 3.5 2 120 6.4 2 209 Table 34 Summary of Clinical Urinalysis Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTARE SMFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day ------ U VOL . ML SP GR U PH ------- -------- -------- 0 MEAN S.D. N 0.03 KEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 41.5 17.76 6 52.5 10.15 4 97.8 71.41 6 93.5 46.63 6 1.026 .0050 6 1.021 .0021 4 1.019 .0078 6 1.018 .0066 6 7.3 .75 6 7.4 .48 4 7.1 .20 6 7.2 .26 6 210 Table 34 Summary of CliniC&l Urinalysis Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID DOSE mg/kg/day ------ U VOL ML -------- SP GR -------- U PH -------- 0 0.03 0.15 0.7S MEAN S.D. N MEAN S.D. N MEAN S.D. N MEAN S.D. N 90.7 75.84 6 92.5 88.38 4 71.8 33.80 6 88.0 78.91 6 1.018 .0060 6 1.019 .0082 4 1.021 .0052 6 1.020 .0069 6 7.3 .41 6 7.1 .25 4 7.8 .42 6 7.3 .41 6 211 Table 35 summary of Clinical urinalysis Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERPLUOROOCTAME SULPCNIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ U VOL ML SP GR U PH -------- -------- -------- 0 0.03 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N MEAN S.D. N 50.2 13.75 6 72.5 29.73 4 94.3 105.16 6 79.0 42.12 6 1.018 .0071 6 1.021 .0040 4 1.019 .0092 6 1.018 .0082 6 7.5 .45 6 7.5 .41 4 7.2 .27 6 7.3 .75 6 212 Table 35 tummary of Clinical Urinalysis Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE ing/kg/day ------ U VOL ML SP GR u PH -------- -------- -------- 0 MEAN S.D. N 0.03 HEM S.D. N 0.15 ME" S.D.. N 0.75 MEAN S.D. N 118.5 218.53 6 86.8 56.91 4 63.7 53.05 6 100.2 155.27 6 1.014 .0103 6 1.018 .0056 4 1.017 .0076 6 1.022 .0094 6 8.0 .32 7.8 .29 4 7.5 .32 6 7.8 .61 6 213 Table 36 Summary of clinical Urinalysis Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFOUIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ U VOL ME. SP GR U PH -------- -------- -------- 0 0.03 mm S.D. N MEAN S.D. N 77.5 50.66 6 62.2 34.86 4 1.018 .0054 6 1.018 .0076 4 8.0 .32 6 8.0 .41 4 0.15 MEAN S.D. N 94.5 59.43 6 1.015 .0095 6 7.8 .42 6 0.75 MEAN S.D. N 68.0 26.39 6 1.017 .0051 6 7.9 .38 6 214 Table 36 Summary of Clinical Urinalysis Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SMFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ U VOL ML SP GR U PH -------- -------- -------- 0 MEAN S.D. N 0.03 . MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 74.3 61.32 6 53.5 32.59 4 62.3 28.06 6 81.0 51.27 6 1.019 .0076 6 1.020 .0056 4 1.020 .0061 6 1.017 .0091 6 8.2 .26 6 7.6 .49 4 7.8 .26 6 7.6 .38 6 215 Table 37 Summary of Clinical Urinalysis Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTANE SULFONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ U VOL ML SP GR u PH -------- -------- -------- 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 KEAN S.D. N 47.5 7.31 6 65.8 40.43 4 101.2 73.16 6 54.0 19.47 6 1.024 .0046 6 1.018 .0062 4 1.014 .0061 6 1.020 .0066 6 7.5 .77 7.8 .29 4 7.4 .49 6 7.2 .88 6 216 Table 37 Summary of Clinical Urinalygig Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTAM SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day ------ U VOL ML SP GR U PH -------- -------- -------- 0 0.03 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N MEAN S.D. N 93.3 68.15 6 64.8 30.02 4 63.2 22.56 6 120.5 125.14 6 1.015 .0053 6 1.018 .0034 4 1.018 .0073 6 1.017 .0096 6 8.0 .00 6 7.4 .48 4 7.5 .63 6 7.8 .42 6 .217 Table 38 Summary of clinical UrinalySia Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID DOSE mg/kg/day ------ U VOL ML -------- SP GR -------- u PH -------- 0 0.03 0.15 0.75 mm S.D. N MEAN S.D. N MEAN S.D. N MEAN S.D. N 131.3 110.42 6 55.0 21.32 4 137.8 114.54 6 180.0 136.48 6 1.013 .0072 6 1.020 .0052 4 1.011 .0062 6 1.011 .0082 6 7.1 .49 6 7.4 .49 4 7.1 .20 6 7.1 .59 6 218 Table 38 summary of Clinical Urinalysis Data Females Day 153 26-WEEX CAPSULE TOXICITY STUDY WITH PERFIUOROOCTANE SULFONIC POTASSIUM SALT (PFOSI T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ U VOL ML SP GR U PH -------- -------- -------- 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 85.2 53.91 6 60.5 36.93 4 40.7 11.15 6 89.0 93.46 6 1.016 .0084 6 1.016 .0029 4 1.022 .0040 6 1.017 .0095 .6 7.5 .32 6 7.0 .41 4 7.1 .20 6 7.1 .66 6 219 Table 39 Summary of Clinical Urinalysis Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ U VOL ML SP GR u PH -------- -------- -------- 0 0.03 0.15 KEAN S.D. N MEAN S.D. N MEAN S.D. N 116.2 79.33 6 75.5 26.20 4 122.3 125.43 6 1.014 .0072 6 1.017 .0022 4 1.013 .0053 6 7.9 .20 6 7.9 .25 4 7.5 1.00 6 0.75 MEAN S.D. N 121.0 108.83 4 1.013 .0059 4 7.2 .65 4 220 Table 39 summary of Clinical Urinalysis Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH IERFLUOROOCTAM SULFMIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID DOSE mg/kg/day ------ U VOL ML SP GR U PH -------- -------- -------- 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 85.7 40.59 6 76.2 31.48 4 73.3 25.33 6 131.8 156.54 6 1.016 .0050 6 1.016 .0054 4 1.017 .0055 6 1.014 .0058 6 8.1 .20 6 7.6 .48 4 7.9 .20 6 7.8 .26 6 221 Table 40 Summary of Clinical Urinalysis Data males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PE"LUOROOCTANS SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS DOSE mg/kg/day ------ U VOL ML SP GR U PH -------- -------- -------- 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 179.5 24.75 2 239.5 79.90 2 87.5 36.06 2 1.010 .0000 2 1.007 .0020 2 1.013 .0028 2 7.2 .35 2 7.5 .00 2 7.0 .71 2 .222 26-WEEK Table 40 Summary of Clinical Urinalysis Data Females Day 217 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ U VOL ML SP GR u PH -------- -------- -------- 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 KFM S.D. N 143.0 77.78 2 121.0 80.61 2 99.0 36.77 2 1.014 .0078 2 1.015 .0000 2 1.015 .0000 2 7.8 .35 2 7.2 .35 2 7.5 .71 2 223 26-WEEK Table 41 Summary of Clinical urinalysis Data Males Day 245 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ U VOL ML SP GR U PH -------- -------- -------- 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 195.5 9.19 2 196.0 132.94 2 83.0 29.70 2 1.009 .0014 2 1.010 .0064 2 1.017 .0042 2 7.8 .35 2 7.5 .00 2 7.8 .35 2 224 26-WEEK Table 41 Summary of Clinical Urinalysis Data Females Day 245 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ U VOL ML -------- SP GR -------- U PH -------- 0 0.15 MEAN S.D. N ME.AN s D. N 117.0 100.41 2 131.5 62.93 2 1.010 .0113 2 1.016 .0021 2 8.0 .00 2 7.2 .35 2 0.75 MEAN S.D. N 91.5 46.79 2 1.016 .0035 2 7.8 .35 2 225 26-WEEK Table 42 Summary of Clinical Urinalysis Data Males Day 274 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ U VOL ML SP GR U PH -------- -------- -------- 0 MEAN 284.0 1.004 S.D. 50.91 .0007 N 2 2 6.8 .3S 2 0.15 MEAN S.D. N 234.0 169.71 2 .0042 2 7.2 .35 2 0.75 MEAN S.D. N 67.5 50.20 2 1.018 .0106 2 7.0 .71 2 226 26-WEEK Table 42 summary of Clinical Urinalysis Data Females Day 274 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ U VOL ML SP GR U PH -------- -------- -------- 0 MEAN S.D. N 0.15 KEAN S.D. N 0.75 MEAN S.D. N 141.5 33.23 2 63.5 37.48 2 64.5 58.69 2 1.006 .0014 2 1.020 .0050 2 1.010 .0007 2 7.8 .35 2 7.5 .00 2 7.2 1.06 2 227 26-WEEK Table 43 Summary of Clinical Urinalysis Data Males Day 322 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ U VOL ML -------- SP GR -------- U PH -------- 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 296.0 254.56 2 99.5 94.05 2 47.5 4.95 2 1.008 .0092 2 1.016 .0099 2 1.020 .0092 2 6.8 .35 2 6.5 .71 2 6.0 .00 2 228 26-WEEK Table 43 Summary Of Clinical Urinalysis Data Females Day 322 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWE SULFOUIC POTASSIUM SALT (PFOS; T-6295) IN CYNO14OLGUS ACID DOSE mg/kg/day ----- U VOL ML -------- SP GR -------- u PH -------- 0 0.15 0.75 MEAN S.D. N MEAN S.D. N MEAN S.D. N 220.5 188.80 2 59.0 24.04 2 92.0 29.70 2 1.006 .0050 2 1.018 .0042 2 1.014 .0035 2 8.0 .00 2 6.5 .71 2 6.8 .35 2 229 26-WEEK Table 44 Summary of Clinical Urinalysis Data Males Day 364 CAPSULE TOXICITY STUDY WITH PERFF.UOROOCTAKE SUI.FONIC ACID POTASSIUM SALT (PFOSI T-6295) IN CYNOMOLGUS DOSE mg/kg/day ------- U VOL ML SP GR u PH -------- -------- -------- 0 0.15 MEAN S.D. N MEAN S.D. N 206.5 81.32 2 74.5 10.61 2 1.017 .0028 2 1.018 .0000 2 7.8 .35 2 7.5 .71 2 0.75 MEAN S.D. N 90.0 14.14 2 1.018 .0050 2 6.8 1.06 2 230 26-WEEK Table 44 Summary of Clinical Urinalysis Data Females Day 364 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOIGGUS ACID DOSE mg/kg/day ------ 0 VOL ML -------- SP GR -------- U PH -------- 0' 0.15 0.75 MEAN S.D. N mm S.D. N MEAN S.D. N 158.0 11.31 2 68.5 13.44 2 76.0 46.67 2 1.011 .0000 2 1.021 .0014 2 1.018 .0007 2 8.0 .00 2 7.0 .00 2 7.0 .71 2 231 26-WEEK Table AS Summary of Clinical Urinalysis Data Males Day 456 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ U VOL ML -------- SP GR -------- u PH -------- 0 0.15 0.75 MEAN S.D. N MEAN s.D. N MEAN S.D. N 185.0 120.21 2 182.0 147.08 2 84.0 8.49 2 1.010 .0028 2 1.008 .0050 2 1.012 .0050 2 8.0 .00 2 0.0 .00 2 8.0 .00 2 232 26-WEEK Table 45 Summary of Clinical Urinalysis Data Females Day 456 CAPSULE TOXICITY STUDY WITH JERFLUOROOCTME SULFONIC POTASSIUM SALT (PPOSI T-6295) IN CYNOMOLGUS ACID DOSE mg/kg/day ------ U VOL ML SP GR U PH -------- -------- -------- 0 MEAN 214.0 1.009 S.D. 164.05 .0057 N 2 2 8.0 .00 2 0.15 MEAN S.D. N 145.0 74.95 2 1.011 .0042 2 7.8 .35 2 0.75 MEAN S.D. N 118.0 82.02 2 1.005 .0042 2 8.0 .00 2 233 26-WEEK Table 46 Summary of Clinical UrinalysiS Data males Day 546 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPCNIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID DOSE mglkg/day ----- U VOL ML SP GR u PH -------- -------- -------- 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 430.0 70.71 2 300.0 148.49 2 222.5 173.24 2 1.005 .0000 2 1.006 .0028 2 1.010 .0071 2 8.0 .00 2 7.8 .35 2 8.0 .00 2 234 26-WEEK Table 46 Summary of Clinical Urinalysis Data Females Day 546 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUN SALT (PFOS; T-6295) IN CYNONOLGUS ACID DOSE mg/kg/day ------ U VOL NL SP GR U PH -------- -------- -------- 0 MEAN S.D. N 0.15 NEAN S.D. N 0.75 NFJKN S.D. N 132.5 38-89 2 67.5 24.75 2 99.0 80.61 2 1.011 .0057 2 1.018 .0014 2 1.014 .0050 2 8.0 .00 2 8.0 .00 2 8.0 .00 2 235 Table 47 Summary of palmitoyl coA oxidase Determinations Terminal Sacrifice males 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID DOSE mg/kg/day ------ PCOAO IU/G -------- 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 5 1.5 4 5 1.0 4 6 6 7 1.4 2 236 Table 47 summary of Palmitoyl CoA oxidase Determinations Terminal Sacrifice Females 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFMIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOL.GUS MONKEYS ACID DOSE mglkg/day ------ PCOAO IU/G -------- 0 MEAN 4 S.D. N 4 0.03 MEAN 4 S.D. 1.3 N 4 0.15 WEAN 6. S.D. 10 N 4 0.75 KEAN S.D. N 6 .8 4 237 TABLE 48 summary of organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNO14OLGUS MONKEYS ------------------------------------------------------------------------------------ -------------------------- TABLE INCLUDESI SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=TISUBSET=ALL LEFT ADRENAL - --- --- -- --- -- ---- --- --- -- --- -- -- -- -- --- -- --- -- --- -- - TERMINAL ORGAN ORGAN-TOBODY WT ORGAN-TOBRAIN WT SEX DOSE TERMINAL BODY Wr ORGAN WEIGHT ORGA BOE SEX DOSE GROUP BODY WT ig) WEIGHT (g) (t) RATIO GROUP (g) (g) ------------------------------- ------------ --------------------------------------------------------------- m 1 --- ---- -- -- --- --- ---- -- -- --- --- NUMBER IN GROUP: MEAN: 4 3540.0 4 0.2858 4 0 0083 4 0.0045 STANDARD DEV: 765.9 0.0195 0:0012 0.0002 F 1 - --- -- --- -- -- -- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2821.3 304.9 --- -- -- 4 4 0.2933 0. 0.0650 0. ------------------------------------------------------------------------------------------------------------- m 2 - ---- -- --- -- ---- --- --- -- ---- -- - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 0.3105 0.0367 4 0.0087 0.0015 4 0.0051 0.0008 F 2 -- --- -- -- --- -- ---- -- -- - NUMBER IN GROUP: 4 a 4 MEAN: 2988.8 * 0.3815 0. STANDARD DEV: 723.4 0.0508 0. ------------------------------------------------------------------------------------------------------------ m- - -3 - - - - - - - - - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: MEANT STANDARD DEV: 4 3190.0 199.6 4 0.2692 0.0298 4 0.0084 0.0006 4 0.0043 0.0003 F 3 --- --- - --- --- --- -- --- - NUMBER IN GROUP: 4 4 4 KEAN: 2768.8 0.3400 0 STANDARD DEV: 335.9 0.0589 0 ---------------------------------------------------------------- ----- ------------ ------------------------- 238 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ---------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL LEFT ADRENAL ---- -- --- ---- -- ---- --- -- --- --- -- TERMINAL ORGAN ORGAN-TO- ORGAN-TO- SEX DOSE 13ODY WT WEIGHT 13ODY WT BRAIN WT GROUP (g) (g) (t) RATIO ---------------------------------------------------------- --- m 4 -- --- -- --- -- --- --- -- -- -- TERMINAL ORGAN ORGJU SEX DOSE BODY WT WEIGHT BODI GROUP (g) (a) ---------------------------------------------- r- - -4 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - - NUMBER IN GROUP: 2 2 2 2 NUMBER IN GRMOEUAPN:- 26534.6 40.3468 40. MEAN: 3077.5 0.3665 0.0120* 0.0003 0.0055 0.0012 STANDARD DEV: 403.1 0.0265 0. STANDARD DEV: 1120.8 0.1237 --------------------------------------------------------------------- --------------------------------------- 239 TABLE 48 Silmmary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS,T-6295) ]IN CYWMOLGUS SULFONIC MONKEYS ----------- ------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL RIGHT ADRENAL -- ---- -- --- ---- -- --- ---- -- ---- -- TERMINAL ORGAN ORGAN-TO- SEX DOSE BODY WT WEIGHT BODY WT GROUP (g) (g) (t) ------------------------------------------------ ORGAN-TOBRAIN WT RATIO -------- -- -- -- --- -- 7 -- -- --- -- -- - TERMINAL ORGAN ORGAN SEX DOSE BODY WT WEIGHT BODY GROUP (9) (g) (t ---------------------------------------------- m I - --- -- ---- --- -- ---- --- -- --- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3540.0 765.9 4 0.2093 0.0503 4 0.0059 0.0011 4 0.0033 0.0008 F 1 --- -- -- -- --- --- -- -- --- NU14BER IN GROUP: 4 4 4 MEAN: 2821.3 0.2178 0.0 STANDARD DEV: 304.9 0.0772 0.0 -------------------------------- ----------------------------- ----------------------------------------------- m 2 -- ---- -- -- ----- -- -- ---- --- --- -- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524'.0 4 0.2240 0.0243 4 0.0063 0.0012 4 0.0036 0.0005 F 2 -- -- --- -- -L --- -- -- --- -- NUMBER IN GROUP: 4 4 4 MEAN: 2988.8 0.2768 0 STANDARD DEV: 723.4 0.0356 o: -------------------------------------------------------------- ---------------------------------------------- m 3 --- --- -- --- ---- -- --- --- --- --- -- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.9 4 0.2135 0.0484 4 0.0067 0.0014 4 0.0033 0.0006 p 3 -- --- -- -- --- -- --- -- -- -- NUMBER IN GROUP: 4 4 4 MEAN: 2768,.B 0.2425 0. STANDARD DEV: 335.9 0.0377 0. -------------------------------------------------------- --------------------------------------------- 240 TABLE 4 8 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS --------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL RIGHT ADRENAL - ---- -- --- --- - ---- -- --- -- --- -- -- --- -- -- -- ---- -- --- -- - TERMINAL ORGAN ORGAN-TOBODY Wr ORGAN-TOBRAIN WT SEX DOSE TERMINAL BODY Wr ORGAN WEIGHT (g) ORGAN BODY (t SEX DOSE GROUP BODY WT (g) WEIGHT (g) - (%) RATIO GROUP (g) ------- -------------------------------------- -------------------------------------------------------------- m 4 p 4 - ---- -- --- ----- - --- --- --- -- --- NUMBER IN GROUP: MEAN: STANDARD DEV- 2 3077.5 1120.8 2 0.2725 0.0686 2 0.0090 0.0011 2 0.0041 0.0006 ---------------------------------------------------------- - - -- --- --- -- --- --- -- --- - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 4 0.2535 0.0306 4 0.( 0. ---------------------------------------------- 241 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ------ -------------------------------------------------------------------------------------------------------- TABLE INCLUDESSEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL BRAIN - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - - - - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- TERMINAL ORGAN ORG) SEX DOSE BODY WT WEIGHT BODY WT BRAIN WT SEX DOSE BODY WT WEIGHT BO GROUP (g) (g) (t) RATIO GROUP (g) (g) ----------------------I----------------------- --------------------------------------------------------------- m 1 --- -- --- --- --- --- ---- -- --- --- -- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3540.0 765.9 4 63.1425 1.1363 4 1.8330 0.3051 4 1.0000 0.0000 p 1 - --- -- --- -- --- --- -- -- -- NUMBER IN GROUP: 4 4 4 MEANT 2821.3 56.6408 2 ---S-T-AN-D-A-RD----DE-V-:-------3-0-4-.9-------4.-1-7-1-0-------0--- ------------------------------------------------------------- m- - 2 -- - - - - - - - - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 61.7943 5.5692 4 1.7415 0.3701 4 1.0000 0.0000 F 2 -- --- -- --- --- --- -- -- -- NUMBER IN GROUP: 4 4 4 MEAN: 2989.8 60.6083 2 STANDARD DEVI 723.4 2.6726 0 ------------------------------------------------------------------------------------------------------------ m- - 3 -- - - - - - - - - - - - - - - - -- - --- -- --- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 63.3520 5.3720 4 1 9873 0:1406 4 1.0000 0.0000 F 3 --- ---- -- --- -- -- --- -- - NUMBER IN GROUP: 4 4 4 MEAN: 2768.8 58.3910 2 STANDARD DEV: 335.9 3.2163 0 ------ ------------ ---------------------------------------------------------------------------------------- 242 TABLE 40 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL:WEEKS=ALL DEATH=T;SUBSET=ALL BRAIN -- -- --- --- -- --- --- --- -- --- -- --- -- -- -- --- -- --- ---- -- -- - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- TERMINAL BODY WT ORGAN WEIGHT ORGAI BODI SEX DOSE BODY WT WEIGHT BODY WT BRAIN WT RATIO SEX DOSE GROUP (g) (g) ----G-RO-U-P----------------(-g-)-------(-g-)---------(-%-)----------------------- ------------ -------------------------- m 4 F 4 -- --- --- -- -- --- - -- --- -- ---- --- NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 66.2635 7.8154 2.2566 0.5678 2 1.0000 0.0000 -------------------------------- --------------------------- - - - - - - - - - - - - - - -- - -- - - - - NUMBER IN GROUP: 4 4 4 MEAN: 2653.8 57.0957 2. STANDARD DgVt 403.1 2.2179 0. ---------------------------------------------- 243 TA13LE 48 Summary of organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PPOS;T-6295) IN CYROMOLGUS SULPONIC MONKEYS --------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL LF EPIDIDYMIS --- --- -- ---- --- - - --- --- -- --- -- - --- -- -- --- --- -- -- --- -- TERMINAL ORGAN ORGAN-TO- ORGAN-TO- TERMINAL BODY WT ORGAN WEIGHT ORG) so SEX DOSE GROUP BODY WT (g) WEIGHT (g) BODY WT (t) BRAIN WT RATIO SEX DOSE GROUP (g) (g) --------------------------------------------- --------------------------------------------------------------- m -- --- --- --- --- --- --- -- -- ---- -- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3540.0 765.9 4 1.1407 0.5031 4 0 0314 0:0076 4 0.0180 0.0076 - --- -- - --- --- --- -- --- - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2821.3 304.9 -------------------------------------------- --------------------------------------------7----------------- m 2 --- --- -- --- ---- --- --- -- --- ---- - NUMBER IN GROUPI MEAN: STANDARD DEV: 4 3631.3 524.0 4 1.4208 0.9897 4 0.0371 0.0196 4 0.0243 0.0197 P. . .2 . . . . . . . . . . . . . . . . . . . NUMBER IN GROUP: MEAN- STANDARD DEV: 4 2988.8 723.4 ------------------------------------------------------------- --------------------------------------------- m- - -3 - - - - - - - - - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 0.9760 0.0910 4 0.0306 0.0027 4 0.0155 0.0025 F- - -3 - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2768.8 335.9 ----------------------------------------7 ---- ---------------- --------------------------------------------- 244 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFOWIC MONKEYS ------- -------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL LP EPIDIDYNIS ---- --- ----- ---- --- --- -- --- ---- - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- SEX DOSE BODY WT WEIGHT BODY WT BRAIN WT GROUP (g) (g) (t) RATIO ------------------------------------------------------------- m 4 -- --- --- -- --- -- --- -- -- - TERMINAL ORGAN ORGJU SEX DOSE BODY WT WEIGHT BOV GROUP (g) (9) --------------------------------------------- F 4 - --- --- -- ---- ---- --- --- --- --- -- NUMBER IN GROUP: MEAN-. STANDARD DEV: 2 3077.5 1120.8 2 1.3095 1.0812 2 0.0387 0.0210 2 0.0189 0.0141 - -- --- ---- -- -- --- -- -- -- NUMBER IN GROUP: HEANT STANDARD DEV: 4 2653.8 403.1 -------------------------------- ----------------------------- ----------------------------------------7-- 245 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH-PERFLUOROOCTAKE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ------- ------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL RT EPIDIDYNIS - - - - - - - - - - - - - - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- SEX DOSE TERMINAL BODY WT ORGAN WEIGHT ORGA BOD SEX DOSE BODY WT WEIGHT (g) BODY WT (t) BRAIN WT RATIO GROUP (g) (g) ----G-RO-U-P---------------(-g--)----------------------------------------------------------------------------------- m I -- ----- -- -- --- --- ---- -- --- --- -- F 1 - --- -- --- --- --- -- -- --- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3540.0 765.9 4 1.2160 0.4066 4 0.0340 0.0063 4 0.0192 0.0061 NUMBER IN GROUP: HEM: STANDARD DEV: 4 2921.3 304.9 ------------------------------ 7 -------------------------------- H- - -2 - - - - - - - - - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: MEAN* STANDARD DEV: 4 3631.3 524.0 4 1.3563 0.9663 4 0.0353 0.0191 4 0.0232 0.0192 ------------------- -------------------------- F 2 --- - - - - - - - - - - - - - - - - - NUMBER IN GROUPT MEAN: STANDARD DEV: 4 2988.8 723.4 ------------------------------------------------------------------------------------------------------------ m- - -3 - - - - - - - - - - - - - - - - - - - - - - - - - - - - F 3 - --- -- -- --- --- - - -- --- - NUMBER IN GROUP: MEAN: STANDARD DEV: a 3190.0 199.8 4 1.0213 0.0786 4 0 0322 0:0039 4 0.0163 0.0025@ NUMBER IN GROUP: MEAN: STANDARD DEVT 4 2760.8 335.9 ------------------------------------------------------------------------------------------------------------- 246 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ---------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL RT EPIDIDYMIS --- ---- --- -- ---- --- -- --- ---- -- -- -- --- -- ---- -- -- --- --- -- - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- TERMINAL ORGAN ORGAN SEX DOSE GROUP BODY WT (g) WEIGHT (g) BODY WT (t) BRAIN WT RATIO SEX DOSE BODY wr WEIGHT BODY GROUP (g) (9) (t ---------------------------------------------- - --------------------------------------------------------------- m- - -4 - - - - - - - - - - - - - - - - - - - - - - - - - - - - p 4 NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 1.3805 1.3371 2 0.0396 0.0290 2 0.0198 0.0178 -------------------------------------------------------------- - ---- -- -- --- --- -- --- -- - NUMBER IN GROUP: HE": STANDARD DEV: 4 2653.8 403.1 ------- --------------------------------------- 247 TABLE 49 summary of organ weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH-PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT IPFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL LF KIDNEY -- ---- --- -- ---- - --- ---- -- -- --- - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- SEX DOSE BODY Wr WEIGHT BODY WT BRAIN WT GROUP (g) (g) (t) RATIO ------------------------------------------------------------- m- - -I- - - - - - - - - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3540.0 765.9 4 6.2305 0.8729 4 0.1780 0.0147 4 0.0985 0.0120 ------------------------------- ----------------------------- m- - -2 - - - - - - NUMBER IN GROUP: MEAN: STANDARD DEV: --- --- --- --- --- --- --- .4 3631.3 524.0 4 6.6015 0.4812 4 0.1838 0.0231 4 0.1078 0.0163 ------------------------------- ----------------------------- m- - 3 -- - - - - - - - - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: MEANT STANDARD DEV: 4 3190.0 199.8 4 5.8875 0.6683 4 0.1844 0.0157 4 0.0936 0.0150 --- --- -- --- --- -- -- ---- - TERMINAL ORGAN ORG) SEX DOSE BODY WT WEIGHT BOT GROUP (g) (g) --------------------------------------------- F 1 -- -- --- -- -- ---- -- --- -- NUMBER IN GROUP: 4 4 4 14EAN: 2821.3 5.5023 0 STANDARD DEV: 304.9 0.9665 0 -------------------------------------------- F- - 2 -- - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: 4 4 4 MEAN: 2988.9 5.8693 0 STANDARD DEV: 723.4 0.9019 a -------------------------------------------- r- - -3 - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: 4 4 4 MEAN: 2768.8 5.5955 0 STANDARD DEV: 335.9 0.4375 0 ------------------------------------------------------------------------7 ---------------------------------- 248 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ------------------------------------------------------------------------------------------------------------ TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS-ALL DEATH=T;SUBSET=ALL LF KIDNEY - - - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - -- --- -- --- -- -- -TERMINAL -ORGAN - - -ORC-J TERMINAL ORGAN ORGAN-TO- ORGAN-TO- SEX DOSE BODY WT WEIGHT Rol SEX DOSE BODY WT WEIGHT' BODY WT BRAIN WT GROUP (g) (g) GROUP (g) (g) (t) RATIO ---------------------------------------------- --------------------------------------------------------------- m 4 F 4 ---- ---- -- -- --- ---- --- --- -- --- - NUMBER IN GROUP: MEAN-. STANDARD DEV: 2 3077.5 1120.8 2 5.5310 1.3916 2 0.1837 0.0217 2 0.0828 0.0112 ------ ------------------------- ------------------------------ --- --- -- -- --- -- --- -- -- NUMBER IN GROUP: 4 4 4 HEMI 2653.8 5.7638 0 STANDARD DEV: 403.1 0.9586 0 ---------------------------- ------------- 249 TABLE 48 Suimary of organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ----------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL RT KIDNEY --- - -- -- -- ---- --- ---- --- -- -- --- --- -- --- -- -- --- -- --- -- -- TERMINAL ORGAN ORGAN-TO- ORGAN-TO- SEX DOSE BODY WT WEIGHT BODY WT BRAIN WT GROUP (g) (g) (%) RATIO ---------------------------------------------- --------------- m 1 --- --- --- - -- ----- --- --- --- -- -- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3540.0 765.9 4 6.0052 0.9353 4 0.1712 0.0127 4 0.0949 0.0130 TERMINAL ORGAN ORGAN- SEX DOSE BODY WT WEIGHT BODY GROUP (g) (0) (t) --------------------------------------------- F 1 - --- -- --- -- --- --- -- -- -- NUMBER IN GROUP: 4 4 4 MEAN: 2021.3 5.2995 0.1 STANDARD DEV: 304.9 0.7914 0.0 -------------------------------- --------------------------------------------------------------------------- m 2 --- ---- -- -- ---- --- ---- --- -- --- - NUMBER IN GROUP: MEAN- STANDARD DEV: 4 3631.3 524.0 4 6.7495 0.6929 4 0.1875 0.0228 4 0.1104 0.0206 F 2 -- --- --- -- -- --- -- --- -- - NUMBER IN GROUP: 4 4 4 MEAN: 2988.8 5.7718 0.1 STANDARD DEV: 723.4 0.8467 0.0 ------------------------------------------------------------ m- 3 --- -- -- --- ---- --- ---- -- --- --- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 5.7358 0.6730 4 0.1795 0.0140 4 0.0910 0.0131 ------- --------------------------------------- F 3 - - - - - - - --- - - - - - - - - NUMBER IN GROUP: 4 4 4 MEAN: 2768.8 5.4028 0.1 STANDARD DEV: 335.9 0.4663 0.0 ------------------------------------------------------------------------------------------------------------- 250 TABLE 48 Summary of Organ Weight Terminal Sacrifice Data. 26-WEEK ACID CAPSULE TOXICITY . STUDY WITH PERFLUOROOETANE POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS SULFoNrc MONKEYS ---------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=AL.L DEATH=T;SUBSET=ALL RT KIDNEY -- ---- -- -- -- ---- --- ---- -- --- -7 - -- --- -- -- ---- -- --- - TERMINAL ORGAN -- -ORG TERMINAL ORGAN WEIGHT ORGAN-TOBODY WT ORGAN-TOBRAIN WT SEX DOSE BODY WT WEIGHT BOD) SEX DOSE GROUP BODY Wr (g) (g) (%) RATIO GROUP ------- (g) (g) (t ------------- --------------------------------------------------------------- p 4 m 4 -- - -- --- -- --- --- ----- -- -- ----- NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 5.4045 1.2594 2 0.1801 0.0247 2 0.0810 0.0095 ------------------------------------------------------------- -- --- -- -- --- ---- -- -- -- - NUMBER IN GROUP: 4 4 A MEAN: 2653.8 5.7878 0. STANDARD DEV: 403.1 1.1793 0. --------------------------------------------- 251 TABLE 4 8 summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ---------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL LIVER ----- --- ---- --- -- --- ---- -- --- --- - --- -- --- -- --- --- -- --- -- TERMINAL ORGAN ORGAN-TO- ORGAN-TO- TERMINAL BODY WT ORGAN WEIGHT ORGAN BODY SEX DOSE GROUP BODY WT (g) WEIGHT (g) BODY WT (t) BRAIN WT RATIO SEX DOSE GROUP (g) (g) (t ---------------------------------------------- ----- ------------------------------------------------------ m- - -1 - - - - - - - - - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUPMEAN: STANDARD DEV: 4 3540.0 765.9 4 54.9200 1496 4 1.5733 0.2144 4 0.8689 0.1203 F I -- - - -- --- --- --- -- -- --- NUMBER IN GROUP: 4 4 4 HEANs 2821.3 51.0925 1.8 STANDARD DEVI 304.9 9.4330 0.1 ------------------------------8-*------------------------------- ----------------------------------------------- m 2 - - - - -- - - - - - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: MEAN: STANDARD DEV- 4 3631.3 524.0 4 62.0868 5.2757 4 1.7413 0.3311 4 1.0090 0.0994 F ,2 ---- -- -- --- --- -- --- -- -- NUMBER IN GROUP: 4 4 4 MEAN: 2988.8 56.8278 1 STANDARD DEV: 723.4 12.5011 o: ------ --------------------------------------------------------------------------------------------------- m- - -3 - - - - - - - - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 57.3325 5.5102 4 1.7955 0.0901 4 0.9059 0.0581 F- - -3 - - - - - - - - - - - - - - - - - - - - NU14BER IN GROUP: 4 4 4 MEAN: 2768.8 57.0393 2. STANDARD DEVT 335.9 3.1240 0. -------------------------------- ----------------------------- ---------------------------------------------- 252 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ---------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL LIVER --- ---- -- - -- -- --- ---- -- --- ---- - --- -- --- -- --- --- --- -- -- - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- TERMINAL BODY WT ORGAN WEIGHT ORGAD BOD) SEX DOSE BODY WT WEIGHT BODY WT BRAIN WT RATIO SEX DOSE GROUP (g) (g) (I GROUP (g) (g) (t) ---------------------------------------------- ------- ------------------------------------------------------- m 4 p 4 - -- --- --- -- -- --- -- --- - ---- --- -- ---- --2 --- -- --- ---- -- 2 2 NUMBER IN GROUP: 4 4 4 NUMBER IN GROUP: MEAN: 2 3077.5 85.2815 2.7247* 1.2616 HEM: 2653.8 75.2997* 2. 403.1 13.3835 0. STANDARD DEV. 1120.8 38.3702 0.2548 0.4304 ...S.TA.N.D.AR.D...D.EV.:................................ -------------------------------- ----------------------------- 253 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULPONIC MONKEYS -------------------------------- ------------ ----------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL LF OVARY -- --- --- ---- -- -- --- ---- --- -- --- - --- --- -- --- --- -- --- --- - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- TERMINAL ORGAN ORGA BODY Wr WRIGHT BO SEX DOSE GROUP BODY WT (g) WEIGHT (g) BODY WT (t) BRAIN WT RATIO SEX DOSE GROUP (g) (g) ------ --------------------------------------- --------------------------------------------------------------- F. . . . . . . . . . . . . . . . . . . . . . . m 1 ---- --- --- --- -- --- ---- --- -- --- - NUMBER IN GROUP: 4 4 4 NUMBER IN GROUP: 4- twm: 2821.3 0.1688 0. MEAN: 3540.0 STANDARD DEV: 304.9 0.0679 0. STANDARD DEV: 765.9 ------ ------------ ----------------------------------------------------------------------------------------- m- - -2 - - - - - - NUMBER IN GROUPMEAN: STANDARD DEV: ---- -- --- --- --- --- --- 4 3631.3 524.0 F- - -2 - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: 4 4 4 MEAN: 2988.8 0.1723 0. STANDARD DEVT 723.4 0.0729 0. ------------------------------------------------------------ ---------------------------------------------- m- - -3 - - - - - - - - - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: 4 F 3 -- --- -- --- -- --- -- --- - NUMBER IN GROUP: 4 4 MEAN: 2768.8 0.1873 0 MEAN: STANDARD DEV: 3190.0 199.9 STANDARD DEVI 335.9 0.0847 0 -------------------------------------------------- -------------------------------------------------------- 254 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH-PERFLUOROOCTARE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULPONIC MONKEYS --------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL LF (YVARY - - - - - - - - - - - - - - - - - - --- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- TERMINAL BODY WT ORGAN WRIGHT ORGAN BODY SEX DOSE GROUP BODY Wr (g) WEIGHT (g) BODY WT (t) BRAIN WT RATIO SEX DOSE GROUP (g), (g) (t ------- -------------------------------------- --------------------------------------------------------------- m 4 F 4 - --- --- --- -- ---- -- --- ---- -- --- - NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 - - - - -- - - - - - - - - - - - - - - - - - NUMBER IN GROUP: 4 4 4 MEAN- 2653.8 0.1590 0.0 STANDARD DEVI 403.1 0.0563 0.0 ------------------------------------------------------------------------------------------------------------- 255 TABLE 48 summary,of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ----------------------------------------------------------- -------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL RT OVARY - -- --- --- --- --- -- ---- --- --- -- - - - --- --- -- --- -- --- -- --- - - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- TERMINAL BODY WT ORGAN WEIGHT ORGAN BODY SEX DOSE BODY WT WEIGHT BODY WT BRAIN WT RATIO SEX DOSE GROUP (g) (g) (% ----G-R-O-UP-----------------(-g-)--------(-g-)----------(-%-)--------------------------------------------- ----------------------- m 1 -- --- --- --- -- ---- --- --- --- -- --- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3540.0 765.9 F 1 ---- -- -- --- -- --- -- -- --- NUMBER IN GROUP: MEAN: STANDARD DEVs 4 2821.3 304.9 4 0.1423 0.0491 4 00 0:0 -------------------------------------------------------------------------------------------------------------- m- - 2 -- - - - - - - - - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 p- - -2 - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: 4 4 4 MEANT 2988.8 0.1788 0. STANDARD DEV: 723.4 0.0453 0. ------------------------------------------------- ----------------------------------------------------- m 3 F 3 -- -- --- -- -- --- -- --- -- -- -- ---- --- -- ---- -- ----- -- -- --- - NUMBER IN GROUP: 4 4 4 NUMBER IN GROUP: 4 MEAN: 2768.8 0.1367 0. MEAN- 3190.0 STANDARD DEV: 335.9 0.0353 0. STANDARD DEV: 199.8 ---------------------------------------------------------------------------------------------------------- 256 TABLE 48 Summary of Organ Weight Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE ACID POTASSIUM SALT (PFOS;T-:-6295) IN CYNOMOLGUS SULFONIC MONKEYS -------------------------------------------------------------------------------------------------------------- TABLE INCLUDEST SEX=ALL;GROUP=ALL;WEEKS=ALL DFATH=T;SUBSET=ALL RT OVARY - ---- -- -- - -- --- ---- --- --- -- --- - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- SEX DOSE 13ODY WT WEIGHT BODY WT BRAIN WT GROUP (g) (g) (t) RATIO ---------------------------------------------------------- m 4 - -- --- -- --- -- ---- -- --- - TERMINAL ORGAN ORGN SEX DOSE BODY WT WRIGHT BOU GROUP (g) (g) --------------------------------------------- p 4 -- --- -- ---- --- -- NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 - -- --- ---- -- -- ----------------------------------------------------------- - --- -- --- NUMBER IN GROUP: MEAN: STANDARD DEV; -- -- --- -- --- - 4 4 4 2653.8 0.1498 0. 403.1 0.0169 0. --------------------------------------------- 257 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ----------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL LF TESTIS --- --- --- --- ---- -- --- --- --- --- -- -- --- -- -- --- --- --- --- -- - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- TERMINAL ORGAN ORGAN SEX DOSE BODY WT WEIGHT BODY WT BRAIN WT SEX DOSE BODY WT WEIGHT BODY GROUP (g) (g) (t) RATIO GROUP (g) (g) (% ----------------------------------------------- --------------------------------------------------------------- m 1 - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - F 1 --- -- -- -- --- --- --- --- - - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3540.0 765.9 4 6.9795 3.7391 4 0.1918 0.0803 4 0.1100 0.0572 NUMBER IN GROUP: 1 MEAN: STANDARD DEV: 4 2821.3 304.9 -------------------------------------------------------------------------------------------------------------- m 2 - - - - - - - - - - -- - - - - - - - - - - - - - - - - - - - F 2 -- -- -- --- -- --- --- -- --- - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 7.8848 7.4545 4 0.2009 0.1587 4 0.1369 0.1434 NUMBER IN GROUP: MEAN: STANDARD DEV- 4 2988.8 723.4 -------------------------------------------------------------------------------------------------------------- m 3 --- --- -- ---- --- ---- -- --- ---- -- - F 3 --- -- -- --- --- --- -- --- -- NUMBER IN GROUP: MEAN: STANDARD DEV- 4 3190.0. 199.8 4 5.0977 0.6925 4 0.1600 0.0215 4 0.0814 0.0173 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2768.8 335.9 -----------------------------------------------------------------------------------------7------------------- 258 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS -------------------------------- ------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL LF TESTIS --- --- - ---- --- ---- --- --- -- --- -- - - --- -- --- --- -- --- --- --- - SEX DOSE TERMINAL BODY Wr ORGAN WEIGHT ORGAN-TOBODY WT ORGAN-TOBRAIN WT SEX DOSE TERMINAL BODY WT ORGAN WEIGHT ORGM BODI GROUP (g) (g) (%) RATIO GROUP (g) (g) ---------------------- ---------------------- --------------------------------------------------------------- m- - -4 - - - - - - - - - - - - - - - - - - - - - - - - - - - F 4 --- --- -- -- -- --- ---- --- NUMBER IN GROUP: MEAN: STANDARD DEVs 2 3077.5 1120.8 2 7.0340 7.9238 2 0.1946 0.1866 2 0.0998 0.1078 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 --------------------------------------------------------------------------------------------- ------------- 259 TABLE Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH-PERFLUOROOCTAN]3 ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFOUIC MONKEYS -------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL:WEEKS=ALL DEATH=T;SUBSET=ALL RT TESTIS --- -- ---- -- -- ---- -- ---- --- -- --- - -- --- --- --- -- ---- - --- -- - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- SEX DOSE BODY WT WEIGHT BODY Wr BRAIN WT GROUP (g) (g) (%) RATIO ---------------------------7 ----------------------------------- m 1 - --- --- -- -- --- ---- --- --- -- --- - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3540.0 765.9 4 6.7453 3.3813 4 0.1868 0.0764 4 0.1064 0.0519 TERMINAL ORGAN ORGAN SEX DOSE BODY WT WEIGHT BODY GROUP (g) (g) (% ---------------------- ---------------------- F 1 1 -- -- -- --- --- -- --- -- -- - NUMBER IN GROUP: HEM: STANDARD DEV: 4 2821.3 304.9 ----------------------------------------------------- ------------------------------------------------------- m- - 2 -- - - - - - - - - - - - - - - - - - - - - - - - - - - - F- 2 - --- -- --- -- --- -- --- -- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 8.1230 7.2175 4 0.2089 0.1504 4 0.1403 0.1403 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2988.8 723.4 ------- ------------ ------------------------------------------ ----------------------------------------------- m- - -3 - - - - - - - - - - - - - - - - - - - - - - - - - - - F 3 - --- -- --- -- --- -- -- --- -- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 5.0045 0.7091 4 0.1568 0.0194 4 0.0798 0.0163 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2768.8 335.9 ------- ------------ ---------------------------------------------------------------------------------------- 260 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLuoROOCTANS ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC 14ONKEYS ---------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL RT TESTIS -- ---- -- --- -- ---- --- --- --- -- --- - - - - - - - - - - - -- TERMINAL - - -OR-GAN- - - -ORM- - TERMINAL BODY WT ORGAN WEIGHT ORGAN-TOBODY WT ORGAN-TOBRAIN WT SEX DOSE BODY WT WEIGHT BOD) SEX DOSE GROUP (g) (g) (t) RATIO GROUP (g) (g) (I ---------------------------------------------- --------------------------------------------------------------- m 4 F 4 --- -- ---- - ---- -- ----- -- --- -- -- NUMBER IN GROUP: 2 2 2 2 MEAN: 3077.5 6.9155 0.1906 0.0990 STANDARD DEV: 1120.8 7.8977 0.1872 0.1076 -------------------------------- ----------------------------- - --- -- 7 - --- -- --- --- -- - NUMBER IN GROUP: 4 MEANT 2653.8 ...S.TA.N.D.AR.D...D.EV.:.......40.3...1....................... 261 TABLE 48 Summary of Organ weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULPONIC MONKEYS I--------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DRATH=T;SUBSET=ALL PANCREAS -- ---- --- --- --- --- --- --- --- --- -- -- --- -- -- --- -- --- -- --- - TERMINAL ORGAN ORGAN-TO- ORGAN-TOBRAIN WT SEX DOSE TERMINAL BODY WT ORGAN WEIGHT ORGAI BODI SEX DOSE GROUP BODY WT (g) WEIGHT (g) BODY WT (t) RATIO GROUP (g) (g) --------------------------------------------- --------------------------------------------------------------- m- - 1 -- - - - - - - - - - - - - --- ---- -- --- -- NUMBER IN GROUP: MEAN: STANDARD DEVT 4 3540.0 765.9 4 5.4570 0.8021 4 0.1576 0.0319 4 0.0863 0.0119 F 1 - ---- - -- ---- -- -- --- --- - NUMBER IN GROUPs 4 4 4 MEAN: 2821.3 4.4270 0. STANDARD DEV: 304.9 0.4797 0. ------------------------------------------------------------------------------------------------------------ m- - 2 - - - --- ---- --- --- --- -- ---- --- F 2 --- -- -- --- -- --- -- --- -- - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 4.8133 1.3674 4 0.1309 0.0234 4 NUMBER IN GROUP-. 4 4- 4 0.0799 MEAN: 2988.0 5.9208* 0. 0.0298 STANDARD DEV: 723.4 1.0351 0. ------- ------------------------------------------------------ --------------------------------------------- m 3 - ---- -- --- --- ---- --- -- --- ---- -- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 4.3790 1.1403 4 0.1365 0.0294 4 0.0687 0.0138 F 3 - -- --- -- --- --- -- --- -- -- NU14BER IN GROUPT 4 4 4 MEAN: 2768.8 4.6248 0 STANDARD DEV: 335.9 0.4099 o: ---------------------------------------------------------- --- ---------------------------------------------- 262 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH*PERPLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ------------------------------------------------------------------------ ------------ -------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL PANCREAS --- - - -- ---- --- --- ---- -- --- --- -- -- --- --- -- --- -- --- -- -- - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- TERMINAL BODY WT ORGAN WEIGHT ORGAN BODY SEX DOSE BODY Wr WEIGHT BODY WT BRAIN WT RATIO SEX DOSE GROUP (g) (g) (t ----G-RO-U-P---------------(-g--)-------(-g-)---------(-t-)---------------------------------------------------------------- m 4 F 4 -- -- -- - NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 4.1355 1.5450 2 0.1341 0.0014 2 0.0615 0.0161 -------------------------------------------------------------- - --- - -- NU14BER IN GROUP: 4 4 4 MEANT 2653.8 4.3725 0.1 STANDARD DEV: 403,1 0.4273 0.0 ------- --------------------------------------- 263 TABLE 48 summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ----------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL LP THYROID/PARA ---- -- -- --- -- ---- --- --- --- -- --- -- -- -- --- -- --- --- -- --- -- TERMINAL ORGAN ORGAN-TO- ORGAN-TO- SEX DOSE BODY WT WEIGHT BODY WT BRAIN WT GROUP (g) (g) (%) RATIO -------------------------------------------------------------- m I TERMINAL ORGAN ORGAN- SEX DOSE BODY Wr WEIGHT BODY GROUP (g) (g) (t) ---------------------------------------------- p NUMBER IN GROUP: 4 4 4 4 NUMBER IN GROUP: 4 4 4 MEAN: 2821.3 0.2567 0.0 MEAN: 3540.0 0.1675 0.0047 0.0004 0.0026 0.0007 STANDARD DEV: 304.9 0.1415 0.0 STANDARD DEV: 765.9 0.0479 ------------------------------------------------------------------------------------------------------------ m 2 F 2 - - - - - - - - - - - - - - - - - --- - NUMBER IN GROUP: 4 4 4 4 NUMBER IN GROUP. 4 4 4 MEAN: 2988.8 0.2138 0.0 MEAN: 3631.3 0.2750 0.0074 0.0046 STANDARD DEV: 723.4 0.0751 0.0 STANDARD DEV: 524.0 0.1374 0.0028 0.0027 ---------------------------------------------------------------------- ------------ -------------------------- m 3 ----- -- -- ---- -- ---- --- --- --- --- NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 0.2075 0.0792 4 0.0064 0.0022 4 0.0032 0.0011 F 3 --- -- --- -- --- -- - - --- -- NUMBER IN GROUPs 4 4 MEAN: 2768.8 0.1542 0.0 STANDARD DEV: 335.9 0.0382 0.0 -------------------------------------------------------------------------------------------------------------- 264 TABLE 48 summary of Organ weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH-PERFLUOROOCTAWE ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ---------------------------------------------------------------------------------------------------------------- TABLE INCLUDES., SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL LF THYROID/PARA - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - - - - - - - - - - - - - TERMINAL ORGAN ORGAN-TO- ORGAN-TO- TERMINAL ORGAN OROM SEX DOSE BODY Wr WEIGHT BODY WT BRAIN WT SEX DOSE BODY WT WEIGHT BO GROUP (g) (g) (lb) RATIO GROUP (g) (g) --------------------------------------------- --------------------------------------------------------------- m 4 F 4 - -- --- -- ---- ---- --- -- - ---- --- - NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 0.2020 0.1174 2 0.0063 0.0015 2 0.0030 0.0014 -- --- -- --- -- --- --- --- - - NUMBER IN GROUP: 4 4 4 MEAN: 2653.8 0.1872 0. STANDARD DEV: 403.1 0.0463 0. ------------------------------------------------------------------------------------------------------------- 265 TABLE 48 Summary of Organ Weight Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNONOE-GUS MONKEYS ---------------------------------------------------------------7 ----------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL RT THYROID/PARh --- --- -- -- --- ---- -- --- --- --- -- - TERMINAL ORGAN ORGAN-TO- SEX DOSE BODY WT WEIGHT BODY WT GROUP (g) (g) (t) ------------------------------------------------ ORGAN-TOBRAIN WT RATIO ----- -- m 1 ----- -- -- --- ---- --- ---- - ---- -- - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3540.0 765.9 4 0.1690 0.0711 4 0.0046 0.0009 4 0.0027 0.0011 --- --- -- -- -- --- -- -- --- - TERMINAL ORGAN ORGAN SEX DOSE BODY WT WEIGHT BODY GROUP (g) (g) (t ------- ------------------------------------- F 1 --- -- --- -- --- -- -- -- NUMBER IN GROUP: 4 4 4 NEM- 2821.3 0.2455 0.0 STANDARD DEV: 304.9 0.1300 0.0 ----------------------------------------------- ---------------------------------------------------------- -- m- 2 --- -- --- --- --- ---- --- --- -- -- - NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 S24.0 4 0.2632 0.1614 4 0.0070 0.0035 4 0.0045 0.0031 F 2 ---- -- -- --- -- -- --- -- -- - NUMBER IN GROUP: 4 4 4 MEAN: 2988.8 0.2350 0.0 STANDARD DEV: 723.4 0.0815 0.0 ---------------------------------------------------- ------------------------------------------------------- m- - -3 - - - - - - - - - - - - - - - - - - - - - - - - - - - - NUMBER IN GROUP: MEAN: STANDARD DEV- 4 3190.0 199.8 4 0.2575 0.1150 4 0.0080 0.0032 4 0.0040 0.0016 F 3 - -- -- -- --- -- --- -- --- -- NUMBER IN GROUP- 4 4 4 MEAN: 2768.8 0.1332 0. ---S-T-AN-D-A-RD----DE-V-I-------3-3-5-.9------0-.-0-2-7-9 -------0.---- -------------------------------------------------------------- 266 TABLE 48 summary of organ weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH-PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNMOLGUS SULPOWIC MONKEYS ------------------------------------------------------------------------------------------------------------------ TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL RT THYROID/PARA ---- ---- -- -- ---- --- --- --- --- --- - --- --- -- --- -- --- --- --- -- TERMINAL ORGAN ORGAN-TO- ORGAN-TO- TERMINAL ORGAN ORC4N SEX DOSE BODY WT WEIGHT BODY WT BRAIN WT SEX DOSE BODY WT WEIGHT BODY GROUP (g) (g) (t) RATIO GROUP (g) (g) (t ----------------------------------------------- --------------------------------------------------------------- m 4 p 4 --- ---- --- -- --- --- ---- --- -- ---- NUMBER IN GROUP: MEAN - STANDARD DEV: 2 3077.5 1120.8 2 0.2360 0.1556 2 0.0072 0.0024 2 0.0034 0.0019 --- --- -- --- -- --- --- -- -- NUMBER IN GROUP: 4 4 4 MEAN: 2653.8 0.1945 0.0 STANDARD DEV: 403.1 0.0633 0.0 -------------------------------------------------------------------------------------------------------------- 267 TABLE 49 incidence of Macroscopic Observations Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------- ------------------------------------------------------------------------------------------------------- N U N B E R - 0 P -A N IN A L S TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX: GROUP: -------MALE -------I- -2- -3- -4- ------FEMALE ------1- -2- -3- -4- ORGAN AND KEYWORD(S) OR PHRASE NUMBER: 4 4 4 2 4 4 4 A ------- ---------------------------------------------------------------- ** TOP OF LIST ** GENERAL COMMENT (GC) ..............................N.UM.B.ER EXAMINED: NOT REMARKABLE: 4 4 4 2 4 4 4 4 0 0 0 0 0 0 0 0 BONE NARROW SMEAR TAKEN EYES - DAVIDSONS NO MACROSCOPIC LESIONS ANIMAL OBESE LUNG (LU) .......................................N.U.MB.E.R . EXAMINED: NOT REKARKABLE.- 4 4 4 2 4 4 4 4 4 4 4 2 4 4 4 4 2 2 3 0 1 0 1 0 0 0 0 0 0 1 0 a 4 4 4 2 4 4 4 4 3 3 3 2 2 1 1 0 ADHESION(S) RED FOCUS(I)/AREA(S) DARK FOCUS(I)/AREA(S) LIGHT FOCUS(I)/AREA(S) LIVER (LI) ......................................N.U.MB.E.R. EXAMINED: NOT REMARKABLE: 0 1 1 0 2 3 1 0 1 0 0 0 0 0 1 2 0 0 0 0 0 2 1 2 0 0 0 0 0 0 0 1 4 4 4 2 4 4 4 4 4 4 4 0 3 3 4 3 MOTTLED ADHESION(S) LIGHT FOCUS(I)/AREA(S) SPLEEN (sp) ......................................NU.M.BE.R. EXAMINED: NOT REMARKABLET 0 0 0 2 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 0 1 0 0 0 4 4 4 2 4 4 4 4 3 3 4 2 4 4 3 4 LARGE CONTINUED ON NEXT PAGE 1 0 0 0 0 0 0 268 TABLE 49 Incidence of MacroscoPic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANK SULFONIC ACID POTASSIUM SALT (PPOSsT-6295) IN CYNOMOLGUS MONKEYS ------- --------------------------------------------------------------------------------------------------------- N U M B B R - 0 P - A N I NA L 9 TABLE INCLUDES: SEX=ALL:GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX: -------MALE ------GROUP: -1- -2- -3- -4- ORGAN AND KEYWORD(S) OR PHRASE NUMBER: 4 4 4 2 -------------------------------------------------------------------- ** FROM PREVIOUS PAGE ** SPLEEN (SP) ......................................NU.M.BE.R. EXAMINED: NOT REMARKABLET 4 4 4 2 3 3 4 2 LIGHT FOCUS(I)/AREA(S) LN, MESMITERIC (MS) ...............................NU.M.BE.R EXAMINED: NOT REMARKABLE: 0 0 0 0 4 4 4 2 4 4 4 1 DIFFUSELY RED ADRENAL, CORTEX (AC) ..............................N.UM.B.ER EXAMINED% NOT REHARKABLEs 0 0 0 1 4 4 4 2 4 4 4 0 DIFFUSELY STOMACH, GL DARK (ST) .................................N.U.MB.E.R EXAMINED: NOT REMARKABLE: 0 0 0 2 4 4 4 2 4 4 4 2 RED FOCUS(I)/AREA(S) CECLTH (CE) ......................................N.U.MB.E.R . EXAMINED: NOT REMARKABLE: 0 0 0 0 4 4 4 2 4 4 4 2 ------FEMALE ------ -I- -2- -3- -4- 4 4 4 4 4 4 4 4 4 3 4 0 0 1 0 4 4 4 4 4 4 4 4 0 0 0 0 4 4 4 4 4 4 4 2 0 0 0 2 4 4 4 4 3 4 4 4 1 0 0 0 4 4 4 4 4 4 2 3 RED FOCUS(I)/AREA(S) DARK FOCUS(I)/AREA(S) 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 1 269 TA,BE-9 49 Incidence of macroscopic observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOUIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------------ N U N 8 E R - 0 F -A N I N A L S TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX: -------MALE ------- ------FEMALE -----GROUPT -1- -2- -3- -4- -I- -2- -3- -4- ORGAN AND KEYWORD(S) OR PHRASE NLIMBERs 4 4 4 2 4 4 4 4 ----------------------------------------------------------------------- COLON (CO) ...................................N.U.MB.E.R ..E.XA.MINED: NOT REMARKABLE: 4 4 4 2 4 4 4 4 4 4 4 2 4 4 4 3 DARK FOCUS(I)/AREA(S) SKIN (SK) .........................................N.U.MB.ER EXAMINED: NOT REMARKABLE: 0 0 0 0 0 0 a I 4 4 4 2 4 4 4 4 3 4 4 2 4 4 4 2 ABRASION(S)/ULCERATION(S) ALOPECIA-DIFFUSE ALOPECIA-FOCAL 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 TESTIS (TE) ...................................NU.M.BE.R..E.X.AMINED-. NOT REMARKABLE: 4 4 4 3 4 4 2 2 0 0 a 0 0 0 0 0 LARGE ADMSE TISSUE (AT) ............................N.U.MB.E.R..EXAMINED: NOT REMARKABLET 0 1 0 0 0 0 0 0 a 4 4 2 4 4 4 4 4 4 3 2 4 4 4 3 RAISED FOCUS(I)/AREA(S) END OF LIST 0 0 1 0 0 0 0 1 270 TABLE 50 Incidence of MacroscoPic observations Recovery sacrifice 26-WEEK CAPSULE TOXICITY STUDY W3ETH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT IPFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------------ Nux B ER 0 F AN IN AL 8 A TA13LE INCLUDES: SEX=ALL;GROUP=4;WEEKS=ALL DRATH=U;SUBSBT=ALL SEX- KHLE FEMALE GROUP: -4- -4- ORGAN AND KEYWORD(S) OR PHRASE NU14BERt 2 2 ------------------------------------------------------------------ ** TOP OF LIST ** GENERAL COMMENT (GC) ............................NU.M.BE.R..EXAMINED: 2 2 NOT REMARKABLE: 11 NO KHCROSCOPIC LESIONS 11 LUNG (Lu) ....................................1.4.ME.R...E.XA.MINED: 2 2 NOT REMARKABLE- 12 ADHESION(G) 10 LIVER (LI) ....................................NU.M.BE.R...EX.A.MINED: 2 2 NOT REMARKABLE: 21 ADHESIONFS) 0 1 CAVITY, THORACIC (TA) ...........................NU.M.BE.R..EXAMINED: 2 2 NOT REMARKABLE: 1 2 MODULE(G) END OF LIST 1 0 271 TABLE 51 incidence of Microscopic observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPIONIC ACID POTASSIUM SALT (PFOSIT-6295) IN CYNOMOLGUS MONKEYS -------------------------------- ------------------------------------------------------------------------------ NUN BE R- 0F- AN INA LS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T,FIND=ALL;SUBSET=ALL SEX: GROUP: -------MALE -------1- -2- -3- -4- ORGAN AND FINDING DESCRIPTION NUMBER-. 4 4 4 2 ------------------------------------------------------------------------ ** TOP OF LIST ** BONE, FEMUR (FE) .................................N.U.1.4B.ER EXAMINED: NOT REMARKABLE: 4 0 0 2 0 0 0 0 ------FEMALE ------ -1- -2- -3- -4- 4 4 4 4 4 0 0 4 3 0 0 3 --GROWTH PLATE OPEN MARROW, FEMUR (FM) ................................NU.M.BE.R EXAMINEDs NOT REMARKABLE: 4 0 0 2 1 0 0 1 1 0 0 0 2 0 0 1 1 0 0 0 2 0 0 1 MARROW, STERNUM (SE) ..............................N.UM.B.ER EXAMINED: NOT REMARKABLET --HYPOCELLULAR, MARROW BONE, STERNUM (SB) ................................NU.M.BE.R EXAMINED: NOT REMARKABLET 4 0 0 2 4 0 0 4 4 0 0 2 3 0 0 4 0 0 0 0 1 0 0 0 4 0 0 2 4 0 0 4 4 0 0 2 4 0 0 4 EYE (EY) ........................................N.UM.B.E.R . EXAMINED: NOT REMARKABLE: 4 0 0 2 4 0 0 4 4 0 0 2 4 0 0 BRAIN (BR) ......................................N.U.MB.E.R. EXAMINED: NOT REMARKhBLEt --INFILTRATE, LYMPHOHISTIOCYTIC, PERIVASCULAR --INFILTRATE, MACROPHAGES. PIGMENTED, PERI"SCULAR --INFLAMMATION, LYMPHOHISTIOCYTIC 4 0 0 2 4 0 0 4 2 0 0 0 1 0 0 1 0 0 a 1 0 0 0 0 2 0 0 2 3 a 0 2 0 0 0 0 0 0 0 1 272 TABLE 51 incidence of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ------- ------------------------------------------------------------------------------------------------------- NU NB BR -0P -AN IHA LS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL SEX: GROUPT -------MALE ------- ------FEMALE ------1- -2- -3- -4- -I- -2- -3- -4- NUMBER: 4 4 4 2 4 4 4 4 O-R-G-A-N --A-N-D--F-IN-D-I-NG---D-E-S-CR-I-P-TI-O-N------------------------------------------- -=- -=- -=- -=- -=- -=- -=- -=- KIDNEY (KD) ......................................NU.M.BE.R. EXAMINED: NOT REMARKABLEs --INFILTRATE, LYMPHOHISTIOCYTIC --GLONERULOSCLEROSIS --MINERALIZATION, CORTEX --MINERALIZATION, MEDULLA LUNG (LU) .......................................N.U.MB.E.R . EXAMINED: NOT REMARKABLE: --HYPERPLASIA, --FIBROSIS, --FIBROSIS, --INFILTRATE, --HEMORRHAGE LYMPHOCYTIC, PERIBRONCHIOLAR/PERIVASCULAR PLEURAL/SUBPLEURAL INTERSTITIAL MACROPHAGE, ALVEOLAR HEART (HT) ......................................N.U.MB.E.R. EXAMINEDT NOT REMARKABLE: 4 0 0 2 4 0 0 4 2 0 0 1 2 0 0 2 2 0 0 1 1 0 0 0 1 0 0 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 2 4 0 0 2 4 0 0 4 0 0 0 2 2 0 0 2 4 0 0 0 1 0 0 1 0 0 0 0 2 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 4 0 0 2 4 0 0 4 4 0 0 2 4 0 0 4 LIVER (LI) ......................................N.U.MB.E.R. EXAMINED: NOT REMARKABLE: --INFILTRATE, LYMPHOHISTIOCYTIC --GRANULOMA --HYPERTROPHY, HEPATOCELLULAR, --HYPERTROPHY, HEPATOCELLULAR CONTINUED ON NEXT PAGE CENTRILOBULHR 4 4 4 2 4 4 A 4 0 1 3 0 0 0 1 0 4 3 1 0 4 4 3 3 1 0 0 0 0 0 0 0 0 0 0 1 0 0 0 3 a 0 1 1 010 0 1 273 incidence TABLE 51 of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTARE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNO14OLGUS MONKEYS ----------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL SEXT GROUPT NUN BE R -0F -AN INA LS -------KHLE ------- ------FEMALE ------I- -2- -3- -4- -1- -2- -3- -4- ORGAN AND FINDING DESCRIPTION NUMBER: 4 4 4 2 4 4 4 4 ------------------------------------------------------------------------- ** FROM PREVIOUS PAGE ** LIVER (LI) ......................................N.L.I1.4.BE.R EXAMINEDT NOT REMARKABLE: 4 4 4 2 4 4 4 0 1 3 0 0 0 1 0 --VACUOLATION, HEPATOCELLULAR, CENTRILOSULAR --VACUOLATION, HEPATOCELLULAR --STASIS, BILE --DEGENERATION/NECROSIS, HEPATOCELLULAR 0 0 0 1 0 0 0 1 0 1 0 0 1 1 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 1 0 GALLBLADDER (GB) .................................N.U.MB.E.R EXAMINEDs NOT REMARKABLE: 4 0 0 2 4 0 0 4 3 0 0 1 3 0 0 2 --INFILTRATE, LYMPHOHISTIOCYTIC 1 0 0 1. 1 0 0 2 SPLEEN (SP) ......................................NU.M.B.ER.. EXAMINEDT NOT REMARKABLEZ 4 0 0 2 4 0 0 4 4 0 0 2 4 0 0 4 THYMUS (TH) ......................................NU.M.BE.R. EXAMINED: NOT REMARKABLET --CYST --ATROPHY LN, NESENTERIC (MS) .................................NUMBER EXAMINED: NOT REHARKABLET --HEMORRHAOE --INFILTRATE, MACROPHAGE, PIGMENTED 4 4 4 2 4 4 4 4 3 1 1 0 4 0 0 1 0 1 0 1 0 1 1 2 1 2 3 2 0 4 4 3 4 0 0 2 4 0 0 4 2 0 0 1 3 0 0 4 1 0 0 1 0 0 0 0 1 0, 0 1 0 0 0 274 TABLE 51 incidence of Microscopic Observations Terminal Sacrifice -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLOGUS MONKEYS -------------------------------------------------------------------------------------------------------- N UN BER -0 F-AN INA L S TABLE INCLUDES: SEX=kLL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL SEX: GROUP: ------ MALE -------1- -2- -3- -4- ------FEMALE ------I- -2- -3- ORGAN AND FINDING DESCRIPTION NUMBER: 4 a 4 2 4 4 4 4 ------------------------------------------------------------------------- TRACHEA (TR) .....................................NU.M.BE.R. EXAMINED: NOT REMARKABLE: 4 0 0 2 4 0 0 4 1 0 0 0 2 0 0 0 --INFILTRATE, LYMPHOHISTIOCYTIC --INFLAMMATION, ACUTE ESOPHAGUS (ES) ...................................N.UM.B.ER. EXAMINED: NOT REMARKABLE: 3 0 0 2 2 a 0 4 0 0 0 1 0 0 a 0 4 0 0 2 4 0 0 4 4 0 0 2 3 0 0 4 --INFILTRATE, LYHPHOHISTIOCYTIC THYROID (TY) .....................................NU.M.BE.R. EXAMINED: NOT REMARKABLE: 0 0 0 0 1 0 0 0 4 0 0 2 4 0 0 4 4 0 0 2 3 0 0 1 --INFILTRATE, LYMPHOHISTIOCYTIC --CYST, ULTIMOBRANCHIAL PARATHYROID (PT) .................................N.U.M.BE.R EXAMINED: NOT REMARKABLE: 0 0 0 0 1 0 0 1 0 0 0 0 0 0 0 2 4 0 0 2 3 0 0 4 3 0 0 2 3 0 0 4 --CYST ADRENAL, CORTEX (AC) ..............................N.UM.B.ER EXAMINED: NOT REMARKABLE: --HYPERTROPHY, --INFILTRATE, --PIGKENT CORTICAL CELL LYMPHOHISTIOCYTIC 1 0 0 0 0 0 0 0 4 0 0 2 4 a 0 4 2 0 0 2 3 0 0 3 1 0 0 0 1 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 275 TABLE 51 Incidence of Microscopic observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS -------------------------------- ------------------;-------------------------------------------------------------- N UM BER -0F -AN INA L S TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL SEX: GROUP: -------HALE -------1- -2- -3- -4- NUMBER: 4 4 4 2 O-R-G-AN---A-ND---FI-N-D-IN-G---D-ES-C-R-IP-T-I-ON------------------------------------------------=- -=- - - -=- ADRENAL, MEDULLA (MA) .............................N.UM.B.ER EXAMINED: NOT REMARKABLET 4 0 0 2 4 0 0 2 ------FEMALE ------ -1- -2- -3- -4- 4 a -=- -=- 4 0 0 & 4 0 0 4 AORTA (AO) ...................!.....................N.UN.MOBTER REMEAXRAKMAIBNLEED:: --PROLIFERATION, INTIMAL PITUITARY (PI) ...................................N.U.M.BE.R. EXAMINEDT NOT REMARKABLEs 4 0 0 2 4 0 0 4 4 0 0 2 4 0 0 3 0 0 0 0 0 0 0 1 4 0 0 2 4 0 0 4 4 0 0 2 4 0 0 4 SALIV GL, MANDIB (SG) ................................ NUMBER EXAMINED: NOT REMARKABLE: --INFILTRATE, MUSCLE, SKELETAL LYMPHOHISTIOCYTIC (SM) .............................N.U.MB.ER EXAMINED: NOT REMARKABLE: --INFILTRATE, LYMPHOHISTIOCYTIC --DEGENERATION --INFLAMMATION, GRANULOMATOUS --REGENERATION, MYOFIBER --PARASITES, CYST 4 0 0 2 4 0 0 4 0 0 0 1 2 0 0 2 4 0 0 1 2 0 0 2 4 0 0 2 4 0 0 4 3 0 0 @2 2 0 0 2 1 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 1 276 TABLE 51 Incidence of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------- N U N B B R - 0 F -A N I N A L S TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL SEXT GROUP: -------MALE ------71- -2- -3- -4- ORGAN AND FINDING DESCRIPTION NUMBER., 4 4 4 2 =- -=- -=- -=- ------------------------------------------------------------------------ SPINAL CORD (SC) .................................N.U.MB.E.R EXAMINED: NOT REMARKABLE: 4 0 0 2 4 0 0 2 --PIGMENT, NERVE, SCIATIC NEURONAL (SN) ...............................NU.M.BE.R EXAMINED: NOT REMARKABLE: 0 0 0 0 4 0 0 2 4 0 0 2 ------FEMALE ------ -1- -2- -3- -4- 4 4 4 4 -=- -,- -=- -=- 4 4 4 4 3 1 0 2 1 3 4 2 4 0 0 4 4 0 0 4 STOMACH, GL (ST) .................................N.U.M.BE.R EXAMINED: NOT REMARKABLET 4 0 0 2 4 0 0 4 4 0 0 2 4 0 0 A DUODENUM ....................................N.UM.B.ER. EXAMINEDs (DU) NOT REMARKABLE: --INFILTRATE, MACROPRAGE, PIGMENTED PANCREAS NUMBER EXAMINED: (PA) ........................................ NOT REMARKAJBLET --INFILTRATE, LYMPHOHISTIOCYTIC JEJUNUM (JE) .....................................N.UM.B.ER. EXAMINEDs NOT REMARKABLE: --INFILTRATE, MACROPHAGE, PIGMENTED 4 0 0 2 4 @o 0 4 3 0 0 2 2 0 0 1 1 0 0 0 2 0 0 3 4 0 0 2 4 0 0 4 3 0 0 2 4 0 0 4 1 0 0 0 0 0 0 0 4 0 0 2 4 0 0 4 3 0 0 0 1 0 0 1 1 0 0 .2 3 0 0 3 277 TABLE 51 incidence of Microscopic observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULFOMIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYMOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- NUM BB R 0F -AM IMA L S TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL SEX: GROUPT ------- MALE -------1- -2- -3- -4- ------FEMALE ------I- -2- -3- -4- NUMBERT 4 4 4 2 4 4 4 4 O-R-G-AN---A-ND---FI-N-D-IN-G---D-E-SC-R-I-PT-I-O-N-----------------------------------------------=- -=- -=- -=- -=- -,- -=- -,- ILEUM (IL) ......................................N.U.MB.E.R. EXAMINED: NOT REMARKABLEs 4 0 0 2 4 0 0 4 2 0 0 1 1 0 0 2 --INFILTRATE, MACROPHAGE, PIGMENTED CECUM (CE) ......................................N.U.MB.E.R. EXAMINED: NOT REMARKABLE: 2 0 0 1. 3 0 0 2 4 0 0 2 4 0 0 4 3 0 0 2 3 0 0 2 --INFILTRATE, --PARASITISM MACROPHAGE, PIGMENTED COLON (CO) ......................................N.U.MB.E.R. EXAMINED3 NOT REMARKABLE: 1 0 0 0 1 0 0 1 0 0 0 0 0 0 0 1 4 0 0 2 4 0 0 4 2 0 0 2 4 0 0 3 --INFILTRATE, --PARASITISM, EOSINOPHILIC INTRAMUSCULAR RECTUM (RE) ......................................NU.M.BE.R. EXAMINED: NOT REMARKABLE: 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 1 4 0 0 2 4 0 0 4 4 0 0 2 4 0 0 4 SKIN (SK) ............................................ --HYPERPLASIA, EPIDERMAL (ACANTHOSIS) --INFLAMATION. CHRONIC-ACTIVE --ULCERATION --HAIR FOLLICLES, DECREASED NUMBER EXAMINED: NOT REMARKABLE- 4 0 0 2 4 0 0 4 3 0 0 2@ 4 0 0 2 1 0 0 0 0 0 0 0 1 0 0 0 0 0 a 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 278 TABLE 51 Incidence of MicroscOPic ObservatiOnS Terminal Sacrifice 26-WEIEK CAPSULE TOXICITY STUDY WITH PERPLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOt4OLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- NU NB 9R -0F -AN INA L S TABLE INCLUDES: SEX=ALL,GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL SEX: GROUP: -------MALE -------1- -2- -3- -4- NUMBER: 4 4 4 2 ORGAN AND FINDING DESCRIPTION ------------------------------------------------------------------------- MAMMARY, FEMALE (MF) ..............................NU.M.BE.R EXAMINED: NOT REMARKABLE: 0 0 0 0 0 0 0 0 --INFLAMMATION, ACUTE --INFILTRATE, LYMPHOHISTIOCYTIC MAMMARY, MALE (MM) ................................NU.M.BE.R EXAMINED: NOT REMARKABLEs 0 0 0 0 0 0 0 0 2 0 0 1 2 0' 0 1 ------FEMALE ------ -I- -2- -3- -4- 4 4 4 4 4 0 0 4 2 0 0 4 1 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 URINARY BLADDER (UB) ..............................N.UM.B.ER EXAMINEDI NOT REMARKABLE: --INFILTRATE, LYMPHOHISTIOCYTIC UTERUS NUMBER EXAMINED: (UT) ......................................N.O.T..REMARKABLE: --AMYLOID OVARY (OV) ......................................N.U.MB.E.R. EXAMINED: NOT REMARKABLE: .--MINERALIZATION --ANYLOID --ONE EXAMINED 4 0 0 2 4 0 0 4 3 0 0 2 1 0 0 3 1 0 0 0 3 0 0 1 0 0 0 0 4' 0 0 4 0 0 0 0 2 0 0 3 0 0 0 0 2 0 0 1 0 0 0 0 4 0 0 4 0 0 0 0 3 0 0 2 0 0 0 0 1 0 0 2 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 279 TABLE 51 incidence of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PRRFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS M7O-N-K-EY-S----------------------------- ---------------------------------------------------------------------------- N UN BBR -0 F-AN IHA L S TABLE INCLUDES: SEX=ALL;GROUP=ALL;VIEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL SEX: GROUP: -------MALE -------1- -2- -3- -4- NUMBER: 4 4 4 2 O-R-G-AN---A-ND---FI-N-D-IN-G---D-E-SC-R-I-PT-I-O-N----------------------------------------------=--- -=- -=- -=- VAGINA (VA) ......................................NU.M.BE.R. EXAMINED: NOT REMARKABLE: 0 0 0 0 0 0 0 0 ------FEMALE ------ -1- -2- -3- -4- 4 4 4 4 -=- -=- -=- -=- 4 0 0 & 4 0 0 4 CERVIX (CV) ......................................NU.M.BE.R. EXAMINED: NOT REMARKABLE: 0 a 0 0 4 0 0 4 0 0 0 4 0 a 4 PROSTATE (PR) ....................................N.U1.4.BE.R EXAMINED: NOT REMARKABLE: --INFLAMMATION, SEMINAL VESICLES LYMPHOHISTIOCYTIC (SV) .............................N.UM.B.ER EXAMINED: NOT REMARKABLE: 4 0 0 2 0 0 0 0 2 0 0 0 0 0 0 0 2 0 0 2 0 0 0 0 4 0 0 2 0 0 0 0 4 0 0 2 0 0 0 0 EPIDIDYMIDES (EP) .................................NU.M.BE.R EXAMINED: NOT REMARKABLE: --HYPOSPERMIA TESTIS NUMBER EXAMINED: (TE) .......................................... NOT REMARKABLE: --IMMATURE 4 0 0 2 0 0 0 0 3 0 0 1 0 0 0 0 1 0 0 1 0 0 0 0 4 0 0 2 0 0 0 0 3 0 0 1 0 0 0 0 1 0 0 1 0 0 0 0 280 TABLE 51 Incidence of microscopic observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- NUN B ER-0 F-A NIN AL S TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL SEX: GROUP: -------MALE -------I- -2- -3- -4- ------FEMALE ------1- -2- -3- -4- ORGAN AND FINDING DESCRIPTION NUMBER: ------- 7 ---------------------------------------------------------------- ADIPOSE TISSUE (AT) ...............................N.UM.B.ER EXAMINED: NOT REMARKABLET --LYNPHOID CAUSE OF DEATH TISSUE (CD) ...............................N.UM.B.ER EXAMINED: NOT REMARKABLE: 4 -=- 4 -=- 4 -s- o 0 0 0 0. 0 0 0 0 0. 0 0 0 0 0 2 -=- 0 0 0 0 0 4 -=- 0 0 0 0 0 4 -=- 0 0 0 0 0 4 -=- 0 0 0 0 0 4 -.- 1 0 1 0 0 t.N, TRACHEOBRON END OF LIST (TB) ..............................NU.M.BE.R EXAMINED: NOT REMARKABLEs 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 281 TABLE 52 Incidence of microscopic Observations Recovery Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- TABLE INCLUDES: SEX=ALL;GROUP=4;WEEKS=ALL DEATH=U;FIND= ALL;SUBSET=ALL . N UN BBR SEX: MALE FEMALE GROUP: -A- -4- 0F AN IN A LS ORGAN AND FINDING DESCRIPTION NUMBERT 2 2 ------------------------------------------------------------------------- ** TOP OF LIST ** LIVER, BIOPSY' (LIO) ...............................N.UM.B.E.R EXAMINED: NOT REMARKABLE: 2 2 1 2 --PIGMENT, HEPATOCELLULAR LIVER (LI) .......................................NU.M.BE.R.. EXAMINED: NOT REMARKABLE: 1 0 2 2 0 0 --INFILTRATE, LYMPHOHISTIOCYTIC --PIGMENT, HEPATOCELLULAR --HYPERPLASIA, BILE DUCT --INFLAMMATION, EOSINOPHILIC, --FIBROSIS, CAPSULAR PERI-BILE DUCT 2 1 1 0 1 0 1 0 0 1 END OF LIST a The liver biopsy was taken during Week 57 of recovery. 282 APPENDICK 1 Proto@ol Deviations Protocol ProtocolAmendment No. I protocolAmendment No. 2 ProtocolAmendment No. 3 Covance 6329-223 3M T-6295.7 283 ProtocoDleviations Covanc6e329-223 3M T-6295.7 ProtocoL Reserve (Archive)Sample& "These sampleswillbe transferretdothe Sponsor aftercompletionof the in-hfephase." Actual Procedure. These samples were shippedto theSponsor afterthedosingph= was competed, which was priortothe end of thein-lifpehase. Protocol.Dosing Procedures.Method of Administration."OmUy by gelatincapsules, daily(7daystweek)foratleast26 weeks." Actual Procedure. On Day 3, Animal Nos. 105520 (Group 1 rmle)and 105529 (Group I female)did not receivea dose administratiodnue tobleedingand irritatiionthethroal Dosing -wasdiscontinuedforAnimal No. 105530 (Group 1 female)from Days 10 through 14 due toa soreinsideitsmouth. Protocol.Observationof Aninmls. ClinicaOlbservations.'@Onceweekly,each animal willbe observed;abnormal findingsor an indicatiotnhatthe animalwas normal willbe recorded." Actual Procedure..During thecourseofthe study,severalanimals did not have a weekly observationof normal of abnormal recordedon variousscheduleddays. Protocol.Observationof Animals. Ophthalmic Examinations.Beforeinitiatiofn tvamvnt and beforeeach scheduledsacrificet;heanteriorportionof the eye,optic media,and ocularfundus willbe examined usingan indirecotphthalmscope by a boardcertifieodphthahnologist. Actual Procedure. An ophthahnicexaminationwas completed duringWeek 52 instead ofpriortotherecoverysacrificdeuring.Week 79. 284 Protocol Deviations (Continued) Covance 6329-223 3M T-6295.7 Protocol. ClinicalPathology. Frequency. Scheduled Conections. "Once before initiationf treatment;afteratleast30,60, 90, 150,and 180 days of treatment(befbrethe dailydose);and afteratleast30, 60, 90, 135,180,274,and 365 days of recovery" Actual Procedure. On Day 184,urinesampleswere collectedforseveralanimals; however, thesesamples were not requiredby theprotocoland were discarded. Protocol.ClinicalPathology.Tests.Hematology. Eleven hematologicalparameters were to be testedatallintervals. Actual Procedure. In additionto therequiredhematology testsatthepretreatment intervalmean platelevtolume,red blood celldistributiownidth,plateledtistribution width,and plateletcrwietre alsoinadvertentltyestedfor. Protocol.Serum PFOS LevelDetermination.Method ofCollection."Animals willbe fastedovernightb;lood (approximately2 mL) willbe collectedfrom a femoralvein withoutan anticoagulant." Actual Procedure. Animals were not fastedovernightforthe scheduleacollectioonn Day 197;however, animals were fastedthefollowingnightand collectiownas dorieon Day 198. Protocol.Urine and FecesPFOS Level Determination.Method of Collection."Animals willnot be fasted(exceptforthefirsdtay of recovery)u;rine(atleast2 mL) and feces(at least5 g) willbe collectedovernight." Actual Procedure. The amount of urinecollectedwas not documented atthetimeof each collectioannd thereforecannot be verified. 285 ProtocoDleviatio(nCsontinued) Covance6329-223 3M T-6295.7 ProtocoLAdditionFaelcalSample&'7M samplewsilblecollectientdheearly aftemoon afterpans arecleanedinthemorning toensurethattheyareno more than 6 hoursold." ActualProcedure. On Day 160,some fecalawles were collecteidnthelatemorning ratherthantheearlyafternoon. Protocol.InterimLiverBiopsySamples. "KrisJ.Hansen or heralternatweillbe notifierdegardingtheshipmentof thesamples." ActualProcedure. The phone callmade tonotifyKrisJ.Hansen priorto shipmentof thesesampleswas notdocumented and thereforecannot be verified. Protocol.TerminalLiverBiopsySamples."A sampleofliver(approximatelIyg)win be collectebdy biopsyfrom allanimalsinGroups 3 duringrecovery(Week 79,within I day of theserum PPOS bloodcollection)." Actual Procedure. These sampleswere collecteduringWeek 80,and were not collectewdithinone day of theserum PFOS bloodcollection. Protocol.PostmortemProcedures.CellProliferatiEovnaluation."Afterfixation, samplesforproliferaticoenllnuclearantigen(PCNA) evaluatiownillbe embedded in paraffiannd shippedto:" Actual Procedure. PCNA analysiwsas not done forAnimal No. 105509(Group4 male). Protocol.Termination.PostinortePmrocedures.AdditionaLlung TissueSamples."At theterminalnecropsy,a sampleoflung(approximatel5yg) willbecollectefdrom an animalinthehigh-dosegroup.Thissamplewillbe weighed,flash-frozeinnliquid nitrogena,nd storedina freezers,etto maintain-60 to-800C,untilshipped.Thisfrozen 286 Protocol Deviations (Continued) Covance 6329-223 3M T-6295.7 sample, and a sample of lung (approximately I g, storedin fonmdin) from Animal No. 105509.(Group 4 male,diedJanuary 27, 1999) willbe sentseparatelyunder appropriateConditions(ambientorpacked on dry ice)to: KrisJ.Hansen, PhD 3M E. T. & S. Bldg. 2-3E-09 935 Bush Avenue St PauL Minnesota 55106 Telephone: 651.778.6018 Facsimile:651.778.6176 KrisJ.Hansen or her alternatweillbe notifledregardingthe shipmentof the samples." Actual Procedure- This Procedurewas inadvertentlnyot done attheterminalsacrifice; thusno samples were availableforshipment toKrisJ.Hansen, PhD. Protocol.Termination.PostznortemProcedures.TissuePreservation'.Ihe following tissues(when present)from each animal WM be preservedin 10% neutw-buffered fomialin,unlessotherwisespecifiedf,orpossiblefuturemicroscopicexaminatiorl" Actual Procedure. Femoral bone marrow from Animal Nos. 105517,105519,105527 (Group I znales)1,05507,105509,105512 (Group 4 males),105531,105535 (Group I females),105536,105540,and 105551 (Group 4 females);mammary glandfrom Animal Nos. 105508,105519 (Group I rmles),and 105512 (Group 4 niale)a;nd parathyroidfi-om Animal No. 105544 (Group I female)were insufficienlThese tissuest,hereforew,ere not examined microscopicallyA.dditionallyo,ne ovaryof a possibletwo was examined from Animal No. 105536 (Group 4 female).Missing tissueasre listewdith appropriate comments inthepathologydatasheetsfbrindividualanimals.Summary tablesdo not includethem as having been examined. These deviationsarenot expected tohave affectedtheresultsof thestudy. 287 C 0 V AARCF' "@ imogtitopumn SRRVICU compitxv Sponsor: 3M St.PaUl,Minnesota PROTOCOL Study Mde: 26-Week CapsuleToxicitSytudywidiPerfluorooctaSnutlfonicAcid PotassiumSalt(PFOS;T-6295)inCynomolgus Monkeys Date: August 20,1998 PerformingLaboratory: Covance LaboratorieIsnc. 3301Kinsman Boulevard Madison,Wisconsin 53704-2595 LaboratoryStudy Identification: ProposalNo. 90545B Covance 6329-223 SponsorProjectIdentification: 3M StudyNo. T-6295.7 288 Covmm 6329-223 3M T-6295.7 Pan 2 'Study 26-Week Capsule ToidcityStudy withPufluorooctaneSulfoqicAcid Powsium (PFOS; T-6295) in Cynomolgus Monkeys Salt Purpose To assessthe effectof thetestmaterialon critica=lyme levels,hormones,and other selectedbiochemicalparameterswhen admiuisttmddailyby capsuletocyaomolgu monkeys foratle-,a2s6t weeks Spomor 3M Toxicology Services Building220-2E-02,3M Center SL PAUL Minnesota 55144-1000 Study Monitor Andrew bL Sewat, PhD 3M Telepbone No.- 651.575.3161 FacsimileNo.: 651.733.1773 AlternateStudy Mordtor Marvin T. Case,DVM, PhD 3M To)dcology Services TelephoneNo.: 651.733.5180 FacsimileNo.: 651.733.1773 Study Lomtion Covance Labomtories Inc. 3301 Kinsman Boulevard 14adison,Wisconsin 53704-2595 Mailing Address: PO Box 7545 Madison, Wisconsin 53707-7545 289 StudyDhwWr Paw 1.Ilomford,PhD Covance LaboratoriesInc. Telephone No.-.608.241.7207 FacsimileNo.: 608.242.2736 Covm= 6329-223 3M T-6295.7 Paw 3 Study Toodcdogist Dale Aldridge,BS Cova= LaboratoriesInc. Proposed Study Ymetable ExperimentalStartDate: August 26, 1998 In-lifSetartDate: August 26, 1998 In-lifTemiination Date: To be determined Audited DraftReport Date: To be dewxmined ExperimentalTenmination Date: To be determined Regulatory Compliance This studywillbe conducted in compliancewith theEnvironmentalProtectioAngency Good LaboratoryPracticeRegulationsassetfordiinTitle40 ofthe US Code ofFederal RegulationsP,art792, issuedNovember 29, 1983 (effectivDemember 29, 1983),and withany applicableamendments. Aminud Care and Use Statement An proceduresin thisprotocolareincompliancewiththeAnimal WelfareAM Regulations,9 CPR 1-4. In the opinionofthe Sponsor and study directort,he study does not unnecessarilyduplicatra,ny previouswork. QualityAmurance The protocols,tudy conduct,and fmal reportwillbe auditedby theCovance Quality AssuranceUnit(QAU). 7be proliferaticoenllnucleu antigenevaluatirudataand report willbe auditedby the QAU ofPathology AssociatesInternationalT.he dose analysisand serum and Ever PPOS analysisand reportwillbe auditedby theQAU of3M EnvironmentalLaboratories.Ile blood hormone d 0 and reportwillbe aiiiiitbeydft QAU of Ani LyticsInc. 290 77 ----------7-@ TestMaterial Identification Peffluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) Lot Number 71k-l.otnumber willbe maintainedin theraw datEL Pmdty Responsibilitoyfthe Sponsor Covance 6329-223 3M T-6295.7 Puc4 Stabi5ty Responsibilitoyfthe Sponsor Stomp conditions At room temperature Characteristics Informationon synthesismethods, composition,or othercharacteristitchsatdefinethe testmaterialison fUe with the Sponsor. Veldde I&ntirication Lactose Lot Nwnber The lotnumber willbe maintainedinthemw data. Puirity On fUe with themanufacturer Stabi0ty On filewith themanufactumr Storage Conditions At room temperature 291 Covx= 6329-223 3M T-6295J page 5 GelatinCapsules Capsules(SizeNo. 2) obtainedfrom Torpac,Inc.(FairfielNdo,w Jersey)l;otnmnber will be suppliedby themanufacturer.Gelatincapsuleswillbe storedatroom temperature.A copy oftheCertificatoefAnalysisprovidedby themanufacturerwillbe maintainedinthe ditl Reserve (Archive)Samples A msme sample ofeachlotoftestmaterialvehicle,and each test se dilutio(nI g each)wM be talmnand storedatmom temperamm These sampleswM be bwden-ed to the Sponsor aftercompletionof thein-lifpeham. Dispositionof TestMaterial Any rp-maining t--qmaterialwillbe retainedatCovance foruse in possiblefuu= studies. Animals Species Cynomolgw monkey Source Covance Research ProductsInc. Age at lwtiationofTreatment Young adult/adult Weight at LmidationofTreatiTmt ApproximaWy 2 to5 kg Number and Sex 22 males and 22 females Identificaflon CoUu tag Husbandry Houdug Individual-a,nimalswillbe housed in suspended,stainlessted cages.- 292 Con= 632gL223 3M T-Q95.7 P206 Diet Certifiedprimatediet(#8726C@ Harlan Teklad)once ormice daily.I'hedietis routinelyanalyzedby the fornutntionaclomponents ad environmental contaminants.Resultsof specifiednutrientand contaminantanalysesam on fileat Covance-Madison. Fruit,vegetables,or othersupplementsmay be providedbut will not requireanalysis. Water Ad libinm Samples of thewater areroutinelyanalyzedforspecifiednucroo and environmental 7be resultasreon fileatCovance-MadisoiL C.ontaridnant3 7bere areno ]mown cont-qmingriin thedietor wateratlevelsthatmight intedem with thisstudy. FAnviromment Eavirormental controlsfortheanimal room willbe settomsk;ntai1n8 to 29*C, a relativheumidity of 30 to70%, and a 12-hourlight/12-houdrark cycle.The dark cycle may be interruptetdoaccommodate in-lifperocedures. AccUmation Minimum of4 weeks Randoirdzation Animals willbe weighed,stratifiebdy body weight,and allocatedtothenumber-of blocks equaltothenumber of animalstobe selectedforeach group. Animals ineach block willthenbe assignedtogroups usingcomputer-generatedrandom numbers. Jusdfication PPOS isa known hepaticperoxisomeproliferato(rPP)in the mt. When exposed toPP, nonhuman pmnates (suchasthe cynomolgus monkey) respond sundarlytohumans (i.e.l,ow tono hepaticresponse)and thereforearean appropriatehuman surrogate species. 293 Group Designations and Dosage Levels Covance 6329-223 3MT-M95.7 Pm7 Group Dose Uvel (M&glClay)a Toud MaterialDose Level (mvkgldayt Number of Animals Males Females I (r 30a 6' 61 2 0.03 151, 4 4 3 0.15 e 6" 6# 4 0.75 3(f 61 a Dose levelswiU be provided.The controlgroup (Group 1)willreceivean eqwvalent amount of lactoseingelatincapsulesas the totalmaterial2dministeredto Group 4. b 7le low-dose (Group 2) willreceivethetestmaterialdilutedwithlactose (1:499,w:w). c nc'mid-dose (Group 3) and high-dose(Group 4) groupswillreceivethetest . dilutedwith lactose(1:39,w:w). d Two aaimals inGroups 1,3,and 4 designatedas recoveryaniyn2lwillbe treatedfor atImst 26 weeks,then ftattnentwillbe discontinueda,nd the animalswillbe observedforreversibilitpye,rsb==, ordelayedoccurrenceoftoxiceffectsforat least13 weeks posttreatment Based on plasma testniatedallevelsand clinical pathologyfindings,the recoverymay be reduced or extended,atthediscmtion of thestudy directorand afterconsultatiownith the Sponsor. Dosing Procedures Method ofAdndnkstration OraMy by gelatincapsules,daily(7days/week)foratleast26 weeks Reason forDosing Route To compam with datafmm previoustoxicologystudiesusingthe oralroute,which is themost limy routeof exposure Dose Preparation Capsules willbe preparedatleastweekly. 7be sizeand number ofcapsuleswiu'depend on the physicalcharacteristiocfsthetestmaterial,the dose level,and the weight of the monkey. Individualdailydoseswillbe basedon themost recentindividualbody weights,withthe exceptionofbody weight collectiodnays when theprtviousbody weight wM be used. Dose levelswillbe based on thevehicleassuppliedfor Group 1. 294 Covano 829-223 3M T-6295.7 page 9 For the Gmups 2 through4 dose prepuations,thetestmaterialwillbe dissolvedin acetoneand dilutedwith lactose(1:499,1:39,and 1:39,w:w, respectivelyo)nce before initiationfU==ent Dilutionwithlactoseisnecessarytofacilitactaepsule pmpm-Adon. All dose preparationswfflbe storedatroom temperatureuntildosed. Dose Analyses Dose analyseswillbe done by the Sponsor. Homogeneity Samples (approximatelyI g each)willbe collectedfrom thetop,middle, and bottom of thetestmatmiaL/Iactosepreparationsforthelow- and high-dosegroups and analyzed fortestmaterialcontent Allsamples willbe storedatmom temperamm untilanalyzed. Stability Homogeneity samples collectedfrom themiddle ofthepreparationwsfflbe used for theprestudystabilitaynalysis.One setofsamples (approximmly I g each)WM be taken ftom the low- and high-dosetestmateriavlactose-preparatioantsthe end of the in-lifpehase and analyzedfortestmaterialcontenl Sample Shipping Samples wiU be shippedunder ambientconditionsto: KrisJ.Hansm PhD 3M E. T. & S Bldg. 2-3E-09 935 Bush Avenue St Paul,Minnesota 55106 Telephone: 651.778.6018 Facsimile:651.778.6176 KrisJ.Hansen or her altemiltweillbe notifiedregardingtheshipment of thesamples. Analysis of forfta materialcontentwiU be done on thesamples. Resultswillbe pmvided forinclusionin thefinalreporl Obsezvation of Animals C3!idcalObservations Each animalwillbe obswmd twicedaily(am. and p.m.)formortffitaynd moribundity,* fmdings willbe recordedas theyam observed. 295 Covance 6329-223 3MT-095.7 page 9 Each animal wM be observeddailyand food consmnptionwillbe assessedqualita&dy-, abnormal findmgs willbe recordeclOnce weekly,each animalwillbe observed-, abnormal fnxhngs,oran indicatiotnhattheanimalisnound willbe recorded.During treatment,each :knimswkilllbe observed forsips ofpoor healthor abnormal behavior approximately30 to90 minutes afterthelastanimalon testhas been dosed; abnormal fintiingwsillbe recorde& Additiong findingswillbe recordedasthey areobserved. Body Weights Weekly befom initiatioonftreatment,on thefim day oftm=ent, and weekly thereafterA.n additionablody weight willbe recordedon Day -1fortheDay I dose calculations. OphthAWc Exandnaflons Before initiatioonftreatinenatnd beforeeach scheduledsacrificet;he anteriorportion of the eye,opticmedia,and oculu fundus willbe examined using an indirect ophthalmoscope by a board-certifrodphthalmoloosl CffidcalPathology Frequency Unwheduled Collections When possibleb,lood willbe couectedforclinicaplathologytum from ainimski sacrificedatunscheduledintervals Scheduled Collections Once beforeinitiatiofntreatnent;and (beforethe dailydose)afteratleast30, 60, 90, and 180 days oftreatinenta;nd afteratleast30,60, and 90 days of recovery .Method of Collection Anilrnalwsillbe fastedovemight;blood willbe collectefdrom a femoral vein. Anticoagulantwillbe potassimnEDTA forhematologymm. No anticoagulanits requiredforclinicaclhemistrytests.Urine willbe collectedovernighton wet ice: 296 Cova= 6329-221 3MT-@M5.7 Page 10 Tests Hematology red blood cell(erythrocytec)ount hemoglobin hematocrit me= corpuscularvolume mean corpuscwar hemoglobin mean corpuscularhemoglobin concentration platelectount whitebloodcell(le&ocyte)cowt differentiballood cellcount bloodcellmorphology reticulocytceoxmt CHirdcalCbemEs" glucose uma nitrogen cmadnine totalprotein alb ' globuhn totalbihrubizi dirw bilimbin(iftotablffimbinis greaterdm 2.0mg/dL) cholesterol triglycerides alanineaminoumderase aDcaEne phosphatase LVartate-a,mmo glutamylransfimm gamma sorbitodlehydrogenase creatine]dna calcium inorganicphosphorus sodium potassium clilmide bfleacids amylase lipase pan=atic-specifiacmylase Urinalysis appeamce volume (approximately16 hours) glucose ketones specifigcmvity biurubin pH protein blood microscopicexaminationof sediment urobihnogen Blood Hormone Deterndnation Freqlaency" Three timesbeforeinitiatioonf treatment;afteratleast30, 60, 90, and 190 days of treatment;and afteratle= 30, 60, and 90 days ofrecovery 297 Covam d329-223 3M T-6295.7 PallIeI Number ofAminuds All Method ofCoReedon Animalswillbe fasteodvernighbtl;oodwillbecobectefdromafemoraVlC'= Approximately 5 mL ofblood willbe collectewdithoutanticoagulinatnd allowedto clotforserum samples. Sample Handling Samples forserum willbe centff-ugewdithinI hour aftercodection,aW sm= wM be huvezte& Serum willbe &vukd mto two appmmmawy equalahquots and storedin a freezersetto maintain-60 to -80*C untilpacked on dry iceand shipped to: Dr. SarojDas Ani LyticsInc. 200 Ghwd Stmet,Suite200 Gaithersburg,Maryland 20877 Telephone No.: 301921.0168 FacsimileNo.: 301.977.0433 Ani LyticsInc.willbe notifiemdganftg shipmentof samples. Tests Samples willbe wwyzed by Ani Ly&.s Inc.,forcortisol=,wstemne, estra&oi, estrone,estdol,thyroidstimulatinhgormone, tdiodothyroninMe), and thymxin (T4). Serum PFOS Level Detenni@ation F@requency Before initaitionftvatment,and duringWeeks I (Day 7),2,4,6,8,12,16,20,24, 26, 28, 30, 32, 34, and 39. Number of Animals All Method of CoDection Animals willbe fastedovernightb;lood (approximatel2y mL) willbe collectefdrom a femoral vein withoutan anticoagulant. 298 Coraice 6329-223 3M T-M5.7 Pap 12 Sample Handling Samples willbe centrifugewditbinI hour aftercollectiona,nd serum willbe harvested.Serum samples willbe storedin a frm= settomaintain-60 to-800C. Sample Shipping Scum samples willbe packed on dry iceand shippedto: Kds J.Hansen, PhD 3M E. T. & S Bldg. 2-3E-09 935 Bush Avenue St Paul,Mnnesota 55106 Telephone: 651.778.6018 Facsimile: 651.778.6176 Kds J.Hansen orher alternatweillbe nodfiedmgwftg the shipment of thesamples. Analysisofserum forPFOS willbe done on the samples. Resultswillbe provided forinclusioninthefinalreporl Addldonal Serum Collection At scheduled and unschedulednecropsiesb,lood (asmuch aspossible,up to20 mL) wffl be collectedfrom thevena eava withoutan anticoagulanftrom animalsatthedm of exsanguination.Samples willbe centrifugewdithin1 hour aftercorec@dm and se= will be harvested.Serum from each :inim2lwillbe transferreidntoan appropriatecontainer and storedina freezersettomaintain-60 to-80*C untilshippedto the Spowor (KrisJ.Hansen) forpossiblefutureanalysis. Urine and Feces PFOS Level Determination Frequency On thefirstday ofrecoveryand afteratleast6,30, and 90 days of recovery Number of Azdnub AR Method of Collection nim2l-cwillnot be fasted;urine(approximately2 mL) and feces (approximately5 graim)willbe collecteodvernight. 299 Sample Handling Sampleswillbestoreidna freezesrettomaintai-n10to-300C. Covaoc6e329-223 3M T-6295.7 Pao 13 Swnple Shipping Samples willbe packed on dry iceand shippedto: Kzis J.Hansm PhD 3ME.T.&S Bldg. 2-3E-09 935 Bush Avenue St.Paul,Mmesota 55106 Telephone- 651.778.6018 Facsinu'li-6.5-1.778.6176 Kris J.Hansen orher alwxnatewillbe notifiedregardingft shipment of thesamples. Analysis ofurineand fecesforPFOS willbe done on thesamples. Resultswillbe providedforinclusioninthefinalreporl Tern2ination UnschedWed Sacrificeasnd Deaths N=opsies willbe done. Anirn:kltobe sacrificewdiD be anesthefmd withImmmine and xylazine,weighed, bledforrequiredtestsa,nd exsanguinated. Sebeduled Sacrifices After atleast26 weeks oftrea=ent,fouranimals/sWgroup willbe fastedovernight, then anesthetizedwithket:krninaend xylazine,weighed,exsanguinated,and ne=psk& After atleast26 weeks of treatmentand atleast13 weeks wiffioutreauwnt,the remaining animals willbe fastrdovernight,thenanesthefizemdth krtamine and xylazine,weighed, exsanguinated,and necropsied. Postawrtem Procedura Necropsy The necropsy wM includeexaminationof- an orifices cranialcavity externalsurfaceofthe brain;the externalsurfaceof thespinalcord and cut surfacesof the brainand spinalcard willbe examined when tissuetimming isperformed. cervicaltissuesand organs 300 Covanc6e329-223 3M T-6295.7 Page14 thoraciacb,dominala,ndpelvicavitiaensdviscera extww surfaceof thebody nud cavityand pamasal sinuses Organ Weights From each animal atscheduledand unscheduledsacdficest,hefollowingorgans(when present)willbe weighed;pairedorganswillbe weighed sepuately: adrenal(2) brain eodidymis(2) Iddney(2) liver ovary(2) pancreas testi(s2) thyroid(2),witpharathy@d Organ-to-bodyweightpercentagesand organ-to-brawienightratioswillbe cgculatedl PalmitoylCoA Oxidase Deterndnations RepresentativseamplesoftherightIAWW lobeofliverwillbe collectefdrom each 2nimsl atthe scheduledsacrificew,eighed,flash-frozeinnliquidnitrogen,and storedin a freezersettomaintain-60 to-80cC untilanalyzedforpalmitoylCoA oxidaseactivity. Cen ProliferatioEnvaluation Representativesamples oftheleftlateralobeof theEver,leftand rightwstw, and pancreaswillbe collectedand preservedinzincfomulin. Afterfixations,amplesforproliferaticoenllnuclearantigenTCNA) evaluationwillbe embedded inparaffinand shippedto: Sandra P, Eldridge,PhD Pathology Associateslnftmational 15 Woman's MM Court suiteI Frederick,Maryland 21701 Telephonw. 301.663.1644exL 2036 Facsimile:301.663.8994 PathologyAssociatesInternationawlillbe noffr4 regardingshipment ofsamples. PCNA evaluationwillbe done on thesamples.Resultswillbe providedforinclusioinn thefinalreporl 301 Coy== 6329-223 3M T-6295.7 pap 5 laverPFOS DeterniinatiOU A section(approximately20 g)ofliverwillbe collectefdrom each 8"iM*latthe scheduledsacrificew,eighed, flash-frozeinnliquidnitrogm and storedina fitewr set tomaintain-60 to -80*C untilshippedwithplma samplesto3M (KrisHamm) for analysis.Resultswillbe providedforinclusioinnthefinalreporl Mssue Preservation Mm followingtissues(when pm=t) from ewh sini-mw2illlbe preservedin 10% neuu-al-buffemdfamwin, unlem otherwisespecifiedf,orpossiblefumm microscopicexamination: adrenal(2) aorta brai,n cecum cervix colon duodenum epididymis(2) esophagus eye [(2)tobe preservedinDavidson's fixativfeorsacrificeadnimalsonly] femur withbone marrow (udcular surfaceof thedistalend) gallbladder heart ileum itiunum Iddney(2) lesions Ever lung mammary eand ovary(2) mesenteticlymph node pancreas Pituitary prostate rectm. salivargyland[mandibulu (2)] sciatincerve seminsdvesicle(2) skeletamluscle (thigh) skin spinalcord (cervicalt,horacica,nd lumbar) spleen sternum with bone marrow stomach testi[s(2)tobe pmserved inBouins' solutiofnorsacrificeskdliTn2i only] thymus thyroid(2)widiparatyroid trachea uriuwy bladder utenis va Bone Marrow Smear From thestemum ofeach animal atunscheduled and scheduledsacrifice(smade and heldforpossiblefuum examination). 302 Covmic6e29-223 3M T-M.7 pay,16 WLstopathology -rissufersomeachanimalinthecontroalndbigh-dongroupwsm beembeddedin paraf5n,sectioneds,tainedwith hema=ylin and eosin,and examined mimscopiedly. -rnsuesfrom allotheranimalswillbe rewned forpossiblket= Reports LetterReport A lettereportwillbe preparedfollowingtheterminalsacrifice. Fhud Report A dmft reportthatincludesthefollowinginformationwillbe preparedand submitted: Experimental Desip and Methods Resaits mortality clinicaolbservations body weights food consumption ophthalmic - ' m clinicaplathologyreswts palmitoylCoA oxidm activities hormone analyses(provicw by Ani Lytics) serum, mine, feces,and liverPFOS levels(providedby 3M) cellproliferatioenvaluations(providedby PathologyAssociatesI[u-uwnadonaI) dose analyses(p@ded by 3M) organ weights organ-to-bodyweight percentages organ-to-braiwneight ratios macroscopic observations microscopicobservations StatisticaElvaluation Levene!sten willbe done totestforvariancehomogeneity. In the caseof heterogeneityofvarianceatp & 0.05,tramformaiionswin be used tdsteaizethe VRria=e- comparison testswilltakevarianceheterogeneitiyntoconsideration- 303 Covm= 6329-223 3M T-M5.7 Pao 17 One-way analysiosf varimce (ANOVA) willbe used (ifapplicablet)o analyzeinitial body weights,palmitoylCoA oxidaseactivitieasn,d continuousclinicaplathology values.IftheANOVA issignificanDtu,metes t-teswtillbe used forcontrolversus treatedgroup comparisons. One-way analysisof covariance(ANCOVA) willbe used toanalyzebody weights, withinitiablody weightsasthecorariateI.fft ANCOVA issignificancto,vadatc,adjustedme= willbe used forcontrolversustreatedgroup comparisons. Group comparisons (Groups 2 through4 versusGroup 1)willbe evaluatedatthe 5.0% twc@-muedprobabilitlyevel.Only datacollectedon or afterthefirsdtay of treatmentwillbe analyzedstatistically. At the end of I year afterissuanceofthe auditeddraftreport,ifno requestedmvwons or instructiontso finaem have be= c by theSponsor,thenthe auditeddraft reportwillbe consideredftd and issuedas thefinalreport,signedby the studydirector, and submittedtothe Sponsor. Amy modificationsorchanges totheauditeddraftreportnxpmsted I year afteri&uu= willbe performed atadditionalcosttothe Sponsor. Record Reftntion AU raw data,documentation,records,protocol,specimens,and finalreportgeneratedas a resultof fts studygeneratedby Covance willbe archivedin thestoragefacilitiOefs Covance fora periodof 1 year followingsubmissionofthe finalreporttothe Sponsor. One year aftersubmissionof thefinalrepom &U ofthe aforementionedmaterialswillbe senttothe Sponsor,and a returnfee willbe chargecl The Sponsor may electtohave the materialsretainedintheCovance archivesfor an additionapleriodoftime,and Covauce willcharge a storagefee.Ifthe Sponsor chooses tohave Covance disposeof the materials,a disposalfeewillbe charged. Allraw datastoredan magneticmedia wM be reblinedby Covance. Within 1 year dtcz submissionofthefinalreport,allofthe aforementionedmaterialsfrom the Sponsoes designees(Ani LytiesIuc.,3M E. T. & S, and PathologyAssociates Intematio willbe senttotheSponsor (Andrew Se=at, PhD, 3M by theSponsoes 304 PROTOCOL APPROVAL Covm= 6329-223 3M T-W5.7 Paw 18 .aA Andmw NL Sewat, PbD Study Monitor 3M Date Fdy ovarn@Labotmotro 305 C 0 V Al t C'E-." TMDff#UAPUMSaRVIC= COMPANY PROTOCOL ANMNDNIENT NO. 1 Covm= 6529-223 3M T-6295.7 26-Week CapsuleToxicityStudywithPerfluorooctanSeulfonicArid PotassiumSak (PFOS; T-6295)inCynomo%w Monkeys Sponsor.Study Momitor. TestingFaciit3r StudyDi-emr. 3K St PauL Kmnesota Andrew K SeacatP,hD Covance LaboratorimInc.,Madison, Vr=onsin Peter J.Thomfbrd,PhD M& amendment modffiesthefollowinpgortionsoftheprotocol EffectivAeugust 20,1"8 1. Page 4,Vddde, Storage Condition& To fiwludethesolventusedto dissolvethe testmaterialbeforembdng withtheI=ose, add thefollowingafterd-dssection. solvent Identification AcrAone Lot Nunibers 71m lotnumbers willbe maintainedintheraw data. Purity On ft withthemanuh=m Stability On Me withthemanufacturer StorageConditions At room temperature 306 Covanc6r3.29-223 3M T-6295.7 ProtocAoml-dmentNo.I PUe2 Cbaracteristics Information synthesmiesthodsc,ompositioonr,othercharacteristthiacts defim thesolventison filewiththe 2. Page 7, Group Desipations and DoMe Levels,Footnote a,Sentence1. To correctan error,deletethissentence. EffectiveSeptember 2,1998 3. Page S, Gelatin Capsules,Sentence 1. To change thesiw of thegeblin capsules,deletethissentm= and replacewith thefollowing. Capsules(SizeNos. 2 or 4) obtaiwd from Torpac,Inc.(FafifmldN,ew lersey)l;ot number willbe suppeed by themani,kcturrr. EffectiveDecen*er 15,1998 4. Page 14, Procedures,CeD ProliferatioEnvaluation, Paragraph 3, Sentence 2. To includeevahutionof slidestainedwith hematoxylinand eosininthePCNA evaluationd,eletethissentenceand replace with thefollowing. PCNA evaluation(includinegxambadon ofsWw stainedwithhematoxyfinand cosin)willbe done on thesampks. EffectiveJanuary 21, 1999 5. Page 10,,CWcal Pathology,Tests,CMcal Chemistry. To brlude an additionaclhnicalchemistrytest,add theforoving. I-ligdhensitylipoprotei(nIHDL) EffectiveJanuary 21 and 28 and February 2,1999 6. Page 12, Urine and Fem PFOS LevelDeterndnation,Sample Shipping. At therequestof the Sponsor to cobectadditionaflecalsamples (effective -January21, 1999) and toclariftyhe sample cobwdon (effective January28 and February 2, 1999),add thefollowingafterthissection. 307 Cmuce 6329-223 3M T-MS.7 ProwcaAlineni4meNnot.I Paju3e AdditionaFlftW Smupla DuriagWeek 23,a freshfecaslampleofatk= 5 g,ifpossl*bwliel,lbe cob=ted from 6 males and 6 femaleseach inthecontroland bigh-dosegroups, survival permitting.The sampleswillbe colectedinthemly afternoonafterpans are ckaned inthemorning to ensurethattheyareno more dm 6 hour3 okL The samples willbe collectedinwhitepolypropylenecontabm and senton dry ice to-. Joe McConnell Porphyrinsand NutritionaClhemistryGroup, layo Clinic 200 FirstStreetSW Rochester,Minnesota 55905 Telephone: 507.284.2150 Lab Telephone: 507.284.3232 Dr. McComell wfflbe contactedbeforesbippingthe samples. EffectiveJanuary 21 and February 12 and 16, 1999 7. Page 9,,ClinicalPathology,Frequency, Sdieduled Collection& To re&a the decisionof theSponsor and theStudy Ditaor to add a collectioinntervaalfter 150 days oftreatment(effectivJeanuary21, 1999),to extend the lengthof recovery(effectivFeebruary 12,1999),and to cbxffythecollectiornequkement (effectivFeebruary 12,1999),deletethetextinthissectionand replacewith ft following. Once @efom initiationf treatment;and afteratk4a 30, 60, 90, 150,and ISO days of treatn=t (beforethedailydose);and afteratkast30, 60,90, 135,and 180 days ofrecovery EffectiveFebruary 10 and 16,1999 S. Page 12, Urine and Feces PFOS LeTd De*xndnation, Method of Collection. To modify the amount of sampleto be coreated(effectivFeebruary 10,1999) and to permitcollectioonfsamplesfrom fastedskniinaoln theEm day of recovery (effectivFeebruary 16, 1999),deletethe textinthissectionand replacewith the following. AnirnalwM not be fasted(exceptforthefirsdtay of recovery);urine(atlem 2 mL) and fe= (atle= 5 g)wM t)6collecteodvernight 308 EffectiveFebruary 12,19" Councc6329-223 3MT-M95.7 ftxocd Amehdment No. 1 Page4 9. Page 7, Crmup Deftmtions and Dosage Leveh, Footnote d. To reflemthe decisionofthe Sponsor and the Study Dhvctor to extendthe lengthof recovery, del-ftthete= inthisfbotnoteand replacewiththefolovkg. d Two -grohnnlin Groups 1,3, and 4 designated as recovery linimg wia be tmated foratk4a 26 weeks,th= treatmentwM be discoviinueda,nd the anim-%lwM be observedforrevtmbifty,perdstem, or delayedoccurrenceof toxiceffectsfor atleast26 weeks posttreatment EffectiveFebruary 12 and 15, 1"9 10. Page ll,,Serum PFOS Level Deterndnatimi@Frequency. To refkxtthe decisionofthe Sponsor and the Study Directorto extendthe lengthof recovery (effectivFeebniw7 12,1999) and to revisethemqukements forthem cobwdons duringrecovery(effec&e Febnury 15,1999),deletethetextinthissectionand replacewith theforowing. Before ini&tionof treatmentd;uringWeeks I (Day 7),2,4, 6,8, 12,16,20,24, 26, and 27 (Day 183) duringtreatment;and duringWeeks 27 QDays 184, 185, and 187),28 (Day 190),29 (Day 197),30 (Day 204),31 (Day 211),35,39,43,47, 51, and 53. ii. Page 13, Terndnation,Scheduled Sacdfices.To reflectthedecisionof the Sponsor and theStudy Directorto extendthelengthofrecovery(eff=tim February12,1999) and to prioridwthe number of animnl designatedforrecovery (effectivFeebruary 15,1999),dekte theten inthissectionand replacewith the following. Afteratlem 26 weeks of uzau=t, up to fouranimWsex/group willbe fasted ovmight, fl= umthebnd withketamme and xybzme, wmghed, and necropsied. After at least26 weeks of treatmentand at kut 26 weeks without ueam=t, two ami=Wsextgroup wM be fastedovernight,dm anesthefizedwith ketamine and xylazine,weighed, exsanguinated,and nempsied. 309 EffectivFeebruary 12 and IC 1"9 Covmm 6329-223 3MT-6295.7 h ICM-1Amendmait No.I page-5 12. Page 10, Blood Hornwne Detern-Anation,Frequency. To reflecthe decision of the Sponsor and the Study Dfi-eaorto extend thelengthof recovery (effecti-m Febmary 12, 1999) and to clariftyhe requiements (effectivFeebruary 16, 1999). deletethe textin thissectionand replacewith the fblloving. Three tin= beforeinitiatioonf treatment;afteratk= 30,60, 90, and 180 days of treatnent;and afta at le= 30, 60, 90, 135, and 180 days of recovery 13. Page 1:4 Urine and Feces PFOS Levd DeWndnatioi4 Frequency. To mff= the decisionof ft Sponsor and the Study Dfiwwr to extend thelengthof recovery (effeedw February 12, 1999) and to clariftyherequkements (effective February 16, 1999),deletethe textin thissectionand replacewith the following. On the fiatday of recoveryand afterat least6,30, 90, 135,and 180 days of recoyery EffectiveFebmary 15, 17, and 18,19" 14. Page 13, Postinortem Procedur es.-To fac&ate a requestby the Sponsor to trander smnples of lung tissue(ef'fectivFeebruary 15 and 19,1999) and g&Mladder and bile(effectivFeebruary 17, 1999),add thefolbwing. AdditionW Lung Mme Sampks At the terminalnecropsy,a smnple of lung (approxhnately5g) wfflbe collected from an animalin the high-dosegroup. Ibis sample wM be weighed, fth-frozen in liquidnitrogm and storedin a fi==r, setto maintain-60 to -80*C, until sh4nx!cL This frozensample and a sample of lung (approxhately I g, storedin formahn) from AnimsilNo. 105509 (Group 4 male, died January27, 1999) wM be sent separatelyunder appropriateconditions(ambientor packed on dry ice)to: Kris L Hansen, PhD 3M&T.&S. Bldg. 2-3E-09 935 Bush Avenue St.PauL Kmnesota 55106 Telephone: 651.778.6018 Facsinule: 651.778.6176 310 Comce 6329-223 3M T-6295.7 PrMcol Am=dmmt No. 1 page A- KrisJ.Hansen or her alternatvevM be noffiedmgarciingft shipment Of the samples. AdditionalGallbladderand BileSamples At the scheduledn=opsies, thegallbladdearnd bilewillbe cokcted and stored accordingtoa specialcollectioannd ftatic)pnrocedm. Fmzm gaMAukkr md bilesamples willbe packed on dry ice and tranderredto- Kxis1.Hansen, PhD 3ME.T.&S Bldg. 2-3E-D9 935 Bush Avenue SL PAUL Nfimwota 55 106 Telephone: 651.778.6018 Facsimile.651.778.6176 Yah L.Hansen or heralternatewillbe noffledregardingtheshipment of the s Effwdve Febmary 24 and March 9,1999 15. Page 13, Postraortem Procedures. To bcihu-te a requestby the Spomsor to prepare(effec&e]Febnwy 24, 1999)and mnsfer (eswtiveMarch 9, 1999) samples of liverforelectronmicroscopy and to prepareno uwder hemtoxyrm and eosin-stainesdlidesforlightmicroscopy (effectivMearch 9, 1999),add the following. Mectron Mcroscopy At the terminalnecropsy,samples of liverwillbe collectedand processedto block stagefor electronmicroscopicevaluation.The tissueblocksand a hemtoxyrm and eosin-stainesdhde forlightmicroscopy willbe ftmnsfen-etdo: Sharon Ambrose DMgon Director Pathology Associates 4915 D. ProspectusDrive Durham. North Carolina 27713 Telephone: 919.544.5257 Facsimile:919.544.3218 311 Covnce 6329-223 3M T-6295.7 ProtocolAirnenAmamtNo. I Pase 7 Tusues willbe processed and evaluatedby electronmicroscopy by Pathology AssociatesImmationg (PAI). A reportwM be providedby PAI forkwhisionin the find report PAI isresponsibleforthe qualityassuranceauditingand of any mw'data or specimens produced by PAL Sharon Ambrose orher ahemate willbe notifiedregardinggm shipment of the samples. EffectivAeprilA 1999 16. Page 16, Reports,StatisticaElvaluation,Paragraph 2, Sentence 1. To add stadstcalanalysisof organ weight and hormone values,deleteti@ssentenceand lacewith thefollowing. One-way analy= ofvanm= (ANOVA) wM be used (ffappbcable)to analym initisbkoldy weights,pahx&oyl CoA oxidaseactivitiecso,ntinuousclinical pathology values,hormone values,and organ weightdata. EffectiveApril 26,1999 17. Page 14, Postmortan Procedures, CeH ProriferatioEnvaluation, Paragraph 1. To add a second setof tissuesforcellproHL-mtic)nevaluationa,dd the followingto thisparagraph. A second setof tissues(representativseamplesof theleftlaterallobe of the liver, leftand righttestesa,nd pancreas)preservedinformalinwithoutzincwillalsobe prep=& EffectiveApril28,1999 18. Page 8, Dose Analyses,StabilityS,entence 2. To change the scheduleforthe returnof the samples,deletethissentenceand replacewiththe following. One setof samples(approximately1 g each)wffibe takenfrom thelow- and high-dosetestmater!&Yhkctospereparationsattheend ofthe tmau=t phue and willbe analyzedfortestmaterialcontent 312 Covznc6e329-223 3M T-6295J ProwcoAlntandmenNto.1 Pay 8 EffectivMeay 6,1999 19. Page 16, Reports,LetterReport. To change thelettereportto an interim report,deletethetextinthissectionand replacewith the fbUovAng. Interim Report An interimreport,includingallhems from theEaW reportas appropriatew.i,llbe preparedfollowingtheterminalsacff=. EffectiveMay 17,1999 20. Page 16, Posbnortem Procedures,Histopathology,Sentence 2. To include targetorgansforsinimqlinthelow- and mid-dosegroups,deletethissentenceand replacewith thefollowing. In additionh,m and thymus forallanirniiinthelow- and mid-dose groups and spirw cord gmy matterfrom femalesinft low- and mid-dose groupswillbe embedded inpuaffin,sectioneds,tahiedwith h=aao)L3& and eosin,and =mnbied n=oscopically. Othertissuesa,s appropriatew,illbe retainedforpossiblefuture examination. EffectiveMay 18,1999 21. Page 3, Proposed Study Mmetabl& To includeproposeddatesforhi-life terminationt,heunauditeddraftinterimreport,and the auditeddraftreport,delete the textinthissectionand replacewiththe following. ExperiniemW StartDate: August 26, 1998 in-lifSetartDate: August 26, 1998 in-hfeTerminationDate: August 27, 1999 Unaudited DraftInterimReport Date: May 11,1999 Audited DraftReport Date: December 28, 1999 ExperimentalTenninationDate: To be determined 313 ANWqDNM4T APPROVAL Covance 6329-223 3M T-6295.7 ProtocoAlmmdment No. I page 9 Andrew IvLSencatPhD StudyMonitor 3M y1.@ord,rateos rly Date D 314 CTn0owVilAuWw'mCvEf.f*N PROTOCOL AMENDNTM NO. 2 Covance 6329-223 1 3M T-6295.7 26-Week CapsuleToxicityStudywithPerfluorooctanSeulfonicAcid PotassiumSalt(PFOS; T-6295)inCynomolgus Monkeys Sponsor. 3M, St.Paa Minnesota StudyMonitor. An&ew M. Seacat,PhD TestingFacffity: Covance I-aboratoriIensc.,Madison,Wisconsin StudyDirector. PeterJ.Thomford, PhD Thisamendment modifiesthefollowingportionsof theprotocol. EffectivFeebmary 19,19" I. Page 9,ObservationofAnimals,CTmicalObservations,Paragraph 2, Sentence 2. To add an observationon theday of scheduledsacrificdee,letethis sentenceand replacewith thefollowing. Once weekly and on theday of scheduledsacrifice,ach animalwillbe observed; abnormalfindingsor an indicatiotnhattheanimalisnormal willbe recorded. EffectivJeune 11,19" 2. Page 11,Blood Hormone Deterndnation,Tests.To add free triiodothyroni(nTe3)and freethyroxin(T4)testsd,eletethetextinthissection and replacewiththeforowing. Sampleswillbe analyzedby Ani LyticsInc.forcortisoltestosteronees,tradiol estronee,striotlhyroidstimulatinhgormone,totaland freetriiodothyroni(nTe3), and totaland freethyroxin(T4). 315 Camce 6329-223 3M T-6295.7 ProtocAomlendmenNto.2 Page2 3. Page16,ReportsF,inalReport,StatisticEavlaluationT.o addrepeated measure statistacaanlalysisof cholesteroalnd totaland freetrhodothyronine(T3), add the followingtothe end of thesection. Cholesteroalnd totaland freetmodothyromne (73) willbe analyzedby repwed measuresanalysisofcovariance(ANCOVA) procedurewithavenge preftatment measurements fortheparametersas covariates.Treatment effectsunder ANOVA orANCOVA procedureswillbe evaluatedatp = 0.05level AR post-hoc control-versus-treated-grmoeuapn comparisons (includingvaluesduring recovery)willbe conducted usingDunnett'smany-on-one tprocedure. Analyseswillbe carriedout with SAS procedurePROC MDCED or BMDP, or both. EffectiveAugust 24,19" 4. Page 7,Group Designationsand Dosage LeveL% Footnote d. To reflecthe decisionof theSponsor and the Study Directortoextend thelengthofrecovery, deletethetextinthisfootnoteand replacewith the following. d Two animalsinGroups 1,3,and 4 designatedas recoveryanimalswM be treatedforatleast26 weeks, thentreatmentwillbe discontinued,and the animalswillbe observed forreversibilitpye,rsistenceo,rdelayedoccurrence of toxiceffectsforatleast52 weeks postavatmenl 5. Page 9, ClinicalPathology,Frequency, Scheduled Collections.To reflectthe decisionofthe Sponsor and the Study Directortoextendthe lengthofrecovery, deletethetextinthissectionand replacewith thefollowing. Once beforeinitiationf treatment;afteratleast30, 60,90, 150,and 180 days of treatment(beforethedailydose);and afteratleast30,60,90, 135,180,274, and 365 days of recovery 6. Page 10,Blood Hormone DeterniinationF,requency. To reflecthedecisionof the Sponsor and the Study Directorto extendthe lengthofrecovery,deletethe textinthissectionand replacewith the following. Tbree timesbeforeinitiationf treatmnt;afteratleast30,60, 90,and 180 days of treatment;and afteratleast30, 60,90, 135,180,274,and 365 days ofrecovery 316 Covanc6e329-223 3M T-6295.7 ProtocAdmendmenNto.2 Page3 7. Page11,SerumPFOSLeveDleterminatiForne,quencTyo.refletchte decisionoftheSponsorandtheStudyDh=wr toextendthelengthofrecovery, deletethetextinthissectionand replacewiththefollowing. Beforeinitiationm.aotfinent;duringWeeks I (Day7),2,4,6,8,IZ 16,20,24, 26,and27 (Day 183)duringuvatrwnt;and duringWeeks 27 (Days184,185,and 187),28 (Day 190),29 (Day 197),30 (Day204),31 (Day211),35,39,43,47,51, 53,57,61,65,69,73,77,and 79 EffectivAeugust 24,1999,and January 12 and 21,2000 8. Page 13,Termination,ScheduledSaaffices.To reflectthedecisioonfthe Sponsorand theStudyDirectortoextendthelengthofrecovery(effective Aupst 24,1"9), toreflectthedecisioonftheSponsortocanceltherecovery necropsy(effectivJeanuary12,2000),and to subsequentlcylariftyherequirement (effectivJeanuary21,2000),deletethetextinthissectionand replacewiththe following. Afteratleast26 weeks oftreatmentu,p tofourwdmaLstsex/groupwillbe &ged overnightthenanesthetizewdithketamineand xylazinew,eighed,exsanguinated, and necropsied. Afteratleast26 weeks oftreatmenatnd atkmt 52 weeks withouttreatmenlthe remaininganimalswillberemoved fromthestudyasfollows. Two animalstseixnGroup I willbe returnedtotheCovance stock. Two animalstseixnGroup 3 willbe umsfmted toa subsequentstudy (Covance6329-268). Two animaLs/seixnGroup 4 willbe fastedova-nightt,henanesthetizewdith ketamineandxylazinew,eighed,exsanpinated,and necropsied. EffectivAeugust 24 and September22,1999 9. Page 12,AdditionalFecalSamples. At therequestoftheSponsortocollect livesramplesby biopsy(effectiAvuepst 24,19") andtomodifytheprocedures (effectiSveptember22,1999),add thefollowingaftetrhisection. 317 Covanc6e329-223 3M T-6295.7 ProtocAomlendmenNto.2 Page4 InterimLiverBiopsySamples A sampleoflive(rapproximateIltyo2 g)willbecollectbeydbiopsyfrom inGroup 4 onlyduringrecovery(Week 57, withinI day of the serum PFOS blood collection)I.bis sample willbe dividedintofourportionsas follows. One subsample willbe preservedin 10% neutral-bufferefdornulline,mbedded in paraffins,ectioneds,tainedwith hematoxylinand eosin(duplicatselideswillbe prepared),and examined microscopically. The second subsample willbe flash-frozeinnliquidnitrogen,and storedina freezer,settomaintain-60 to-80cC, untilshipped foranalysisto: KrisJ.Hansen, PhD 3M E. T. & S. Bldg. 2-3E-09 935 Bush Avenue S.tPauL Minnesota 55106 Telephone No.: 651.778.6018 FacsimileNo.: 651.778.6176 KrisJ.Hansen or her alternatweillbe notifiedregardingtheshipment of the samples. Resultswillbe providedforinclusioninthefinalreport. The thirdsubsample willbe processedtoblock stageforelectronnucroscopic evaluation.7be tissueblocksand a hematoxylinand eosin-stainesdlideforlight microscopy willbe transferretdo: Sharon Ambrose DivisionDirector Pathology AssociatesInternational 4915 D. ProspectusDrive Durham, North Carolina27713 Telephone No.: 919.544.5257 FacsimileNo.: 919.544.3218 Tissueswillbe processedand evaluatedby electronmicroscopy by Pathology AssociatesInternation(aPlAI). A reportwillbe providedby PAI forinclusionin the finalreport.Sharon Ambrose or heralternatweillbe notifiedregardingthe shipment of the samples. 318 Camce 6329-223 3M T-6295.7 Pro=olA dnmatNo.2 Page5 The fourtshubsamplweillbeflash-frozienlniquinditrogeanndstoreidna freezer,setto n-.ainmi-n60 to-800C, and transferretdotheSponsor forpossible futureanalysis. EffectiveJanuary 12 and 2192000 10. Page 12,Interim Liver Biopsy S amples. At therequestof theSponsor tocollect liversamples by biopsy,thenterzninattehestudy and ummfer theanimalsto a subsequentstudy(effectivJeanuary 12, 2000) and to modify the requirement (effectivJeanuary21, 2000),add thefbllowingafterthissection. Terminal Liver Biopsy Samples A sample ofliver(approximately1 g) willbe collectebdy biopsyfrom allanimals inGroups 3 duringrecovery(Week 79, withinI day of theserum PFOS blood collection)T.hissample willbe flash-frozeinnliquidnitrogenand storedina freezers,ettomaintain-60 to -80"C, untilshippedforanalysisto: KrisJ.Hansen, PbD 3M E. T. & S. Bldg. 2-3E-09 935 Bush Avenue SL Paul,Minnesota 55106 Telephone No.: 651.778.6018 FacsimileNo.: 651.778.6176 KrisJ.Hansen or her altematewillbe notifiedregardingtheshipment ofthe samples. Resultswillbe providedforinclusioninthe finalreport. EffectiveJanuary 21,2000 11. Page 12, AdditionalSerum Collection.To reflecthedecisionofthe Sponsor to analyzeadditionaslerum samples forspecifiedthyroidhormones, add following totheend ofthissectiorl An aliquot(0.8rrd)of theadditionaslerum collectiosnamples collectedfrom all animalsfrom Groups 1,2,3 and 4 sacrificeadtthetanninalnecropsywillbe sent on dry iceby the Sponsor toDr. SarojDas, Ani Lytics,fbrfreeT3, freeT4, totalT3, and totalT4 determinations. 319 Covanc6e329-223 3M T-6295.7 ProtocAomlendmenNto.2 Page6 12. Page 12,Urineand FecesPFOS LevelDeterminatioFnr,equency.To reflect ft decisionof theSponsor tocollecta 24-hour urineand fecalsample afterone yearof recovery,deletethetextinft sectionand replacewith thefollowing. On the firstday of recoveryand afteratleast6,30, 90, 135,and 180 days of recovery.In additiona, 24-hour sample of urineand feceswillbe collected beforethecompletionof 52 weeks of recovery. 13. Page 16, Postmortem Procedures, Histopathology. To define the postmortem proceduresforrecoveryanimalsinthehigh-dosegroup,add thefollowingafter ft sectiorl Postmrtem ProceduresforRecovery Animals intheHigh-Dose Group At necropsyof therecoveryanimals inthe high@-dosegroup,procedures (includingorganweightsand collectioonftissuesforhistopathological examination)describedpreviouslyarenotrequired.The fbuowing procedures willbe done. Necropsy The necropsywillincludeexaminationoP allorifices cranialcavity externalsurfilcoef thebrain;theexternalsurfaceofthe spinalcord and cut surfacesofthe brainand spinalcord willbe examined when tissueuimming isperformed cervicaltissuesand organs thoracica,bdozninal,and pelviccavitieasnd viscera externalsurfaceof thebody nasalcavityand pamnasal sinuses Uver Samples A sample of liver(approximatelyI to 2 g) willbe collectedT.hissample willbe dividedintothreeportionsas follows. One subsample willbe preservedin 10% neutml-bufferedformalin,embedded in puaft, sectioneds,tainedwithhematoxylinand eosin(duplicatselideswillbe prepared),and examined microscopically. The second subsample willbe flash-frozeinnliquidnitrogenand storedina freezers,ettomaintain-60 to -80*C, untilshippedforanalysisto: .320 Covanc6e329-223 3M T-6295.7 ProtocAol dmmtNo.2 page7 KrisJ.Hansen,PhD 3M E. T. & S. Bldg. 2-3E-09 935 Bush Avenue SL PauL Minnesota 55106 Telephone No.: 651.778.6018 FacsimileNo.: 651.778.6176 KrisJ.Hansen or her alternatweillbe notifiedregardingtheshipment of the samples. Resultswillbe providedforinclusioninthe finalreporl The thirdsubsample willbe processedtoblock stageforelectronmicroscopic evaluation.The tissueblocksand a hematoxylinand eosin-stainesdlideforlight microscopy willbe transferretdo: Sharon Ambrose DivisionDirector Pathology AssociatesInternational 4915 D. ProspectusDrive Durham, North Carolina 27713 Telephone No.: 919.544.5257 FacsimileNo.: 919.544.3218 Tissueswillbe processedand evaluatedby electronn-Acroscopyby Pathology AssociatesInternation(aPlAI). A reportwillbe providedby PAI forinclusioinn the finalreport.Sharon Ambrose or her alternatweillbe notifiedregardingthe shipment of the samples. Additional Tissue and Sermn Samples Samples of lung,kidney,spleen,thyroid,brain,abdoniinw fat,heart,bile, (approximately3 g each),and serum (asmuch aspossible)willbe collected. These samples willbe flash-frozeinnliquidnitrogenand storedina freezer,setto maintain-60 to -80*C@ untilshipped forpossiblefutureanalysisto: KrisJ.Hansen, PhD 3M E. T. & S. - Bldg. 2-3E-09 935 Bush Avenue St.PauL Minnesota 55106 Telephone No.: 651.778.6018 FacsimileNo.: 651.778.6176 321 Czmce 63"-=3 3MT-M5.7 ProtDcAdnm&=t No.2 Pale8 KrisJ.Hmen samples. or ha &mm willbe noffod regardingtheshipmentof the EffectiveFebruary 11 and 15,2000 14. Page 3,Proposed Study TTmnetabl& To change proposed datesforin-Hfe termination(effectivFeebruary 11,2000) and theauditeddraftreport(effective February 15,2000),deletethe textinthissectionand replacewiththe fodowing. ExperimentalStartDate: August 26, 1998 In-lifSetartDate: August 26, 1998 In-lifTeennina@n Date: Much 7,2000 Unaudited DraftLneidm Report Date: May 11,1999 Audited DraftReport Date: May 29,2000 Ternina6on Date: To be determined AN=qDNMIqT APPROVAL Andrew NC SeacatP,hD Study Monitor 3M 41fetJ,.e;iO&ord,-PhD Study Dfector Cov2nce T-AbomtoriesIn Date s,-LDg,-! Date 322 CThe0 V AM C'E-.'@*'N Dr4v"mBff samom comft%w DRAFT PROTOCOL AMENDMIENT NO. 3 Covance 6329-223 3M T-6295.7 26-Week CapsuleToxicityStudywithPerfluorooctanSeulfonicAcid PotassiumSalt(PFOS; T-6295)inCynomolgus Monkeys Sponsor: 3M, St.Paul,Minnesota Study Monitor. Andrew M. Seacat,PbD TestingFacility: Covance LaboratorieIsnc.,Madison,Wisconsin StudyDirector: PeterJ.Thomford, PhD Thisamendment modifiesthefollowingportionsof theprotocol. EffectiveAugust 20,1998 1. page 16,Reports,Final RepoM StatisticaElvaluadong Paragraph 4. To con-ectan omission,add thefollowingtotheen(tofthesection. Data collecteduringrecoverywillnot be analyzedstatisticadluley tothesmall sample size. EffectiveJanuary 21,2000 2. ProtocolAmendment No. 2,Item 13. To correcta typographicalerror,change thefonttoboldon thefollowingheading. Postmortem Proceduresfor Recovery Anhnah in the Mgh-Dose Group EffectiveFebruary 18,2000 3. Page 17.,Serum PFOS LevelDeterminations,Sample Shipping,Paragraph 3, Sentence 3. To indicattehattheresultosftheSponsor'sanalysisof serum samplesforPFOS willbe reportedseparatelyd,eletethissentenceand replace withthefollowing. Resultswillbe reportedseparately. 323 Covanc6e329-223 3M T-6295.7 ProtocAomlendn=tNo.3 Page2 4. Page 12,InterimLiverBiopsySamples,Paragraph3,Sentence2. To indicate thattheresultsof the Sponsor'sanalysisof the interimliverbiopsy samples will be reportedseparatelyd,eletethissentenceand replacewith the following. Resultswillbe reportedseparately. 5. Page 12,Terminal Liver Biopsy Samples, Paragraph 2,Sentence 2. To indicatethattheresultsof the Sponsor'sanalysisof theterminalliverbiopsy samples willbe reportedseparatelyd,eletethissentenceand replacewith the following. Resultswillbe reportedseparately. 6. Page 15,Postmortem Procedures,Liver PFOS Determinations,Sentence 2. To indicattehattheresultosf theSponsor'sanaly'sisof theliversamples willbe reportedseparatelyd,eletethissentenceand replacewith the following. Resultswillbe reportedseparately. 7. Page 16, Reports, F"uW Report, StatisticaElvWuation, Paragraph 4. To remove repeatedmeasure statisticaanlalysisof cholesteroland totaland free triiodothyronin(eT3) attherequestof theSponsor,deletethefollowing. Cholesteroland totaland freetriiodothyronin(eT3) willbe analyzedby repeated measures analysisof covariance(ANCOVA) procedurewith averagepretreatment measurements fortheparametersascovariates.Treatment effectsunder ANOVA or ANCOVA procedureswillbe evaluatedatp = 0.05 level.Allpost-hoc control-versus-treated-grmoeuapn comparisons(includingvaluesduring recovery)willbe conducted usingDunnett'snany-on-one tprocedure. Analyses willbe carriedout with SAS procedurePROC MDCED or BMDP, or botil EffectivFeebruary 18 and 22,2000 8. Page 16,Reports,FinalReport,Rftmh& To indicattehattheresultosfthe Sponsor'sanalysisof theserum and liversamples (effectivFeebruary 18,2000) and urineand fecessamples (effectivFeebruary22, 2000) willbe reported separatelyd,eletethe following. serum, urine,feces,and liverPFOS levels(pmvided by 3M 324 Covance 6329-223 3M T-6295.7 ProtocolAmendment No. 3 Page 3 9. Page 16, Postmortem Procedures for Recovery Animals in the High-Dose Group, Liver Samples. To indicate thatthe resultsof the Sponsor's analysis of the liversamples willbe reportedseparately(effectivFeebruary 18,2000) and to modify the amount of Ever collectedatnecropsy (effectivFeebruary 22, 2000), deletethetextin thissectionand replacewith thefollowing. Samples of Ever willbe collectedas follows. One saniplewillbe preservedin 10% neutral-bufferefdormalin,embedded in paraffins,ectioned,stainedwith hematoxylin and eosin (duplicateslideswillbe prepared),and exan-dned microscopically. The second sample willbe flash-frozenin liquidnitrogenand storedina freezer, setto maintain -60 to -80*C,untilshipped for analysisto: Kris J.Hansen, PbD 3ME.T.&S. Blog. 2-3E-09 935 Bush Avenue SL PauL Minnesota 55106 Telephone No.: 651.778.6018 FacsimileNo.: 651.778.6176 Kris J.Hansen or her alternatewillbe notifiedregardingdieshipment of the samples. Results willbe reportedseparately. The thirdsample willbe processedto block stagefor electronmicroscopic evaluation.The tissueblocksand a heniatoxylinand eosin-stainedslideforlight microscopy willbe transferredto: Sharon Ambrose DivisionDirector Pathology AssociatesInternational 4915 D. ProspectusDrive Durham. North Carolina 27713 Telephone No.: 919.544.5257 FacsimileNo.: 919.544.3218 Tissues willbe processed and evaluated by electronmicroscopy by Pathology AssociatesInternationa(lPAI). A reportwillbe provided by PAI forinclusionin thefinalreport.Sharon Ambrose or her alternatweillbe notifiedregardingthe shipment of the samples. 325 EffectiveFebruary 22, 2000 Covance 6329-223 3M T-6295.7 ProtocolAmendment No. 3 Page 4 10. Page 13,Urine and Feces PFOS Determination, Sample Shipping, Paragraph 2, Sentence 3. To indicatethattheresultsof the Sponsor's analysis of the urine and fecessamples willbe reportedseparately,delete thissentence and replacewith the following. Resultswillbe reported separately. 11. Page 16,Postmortem Procedures forRecovery Animals In the High-Dose Group, Additional Tissue and Serum Samples, Paragraph 1. To modify the amount of tissuecollectedatnecropsy,deletethisparagraph and replacewith the following. Samples of lung,kidney, spleen,thyroid,brain,abdominal fat,heart, (approximately3 g each, ifpossi7ole)a,nd bileand serum (each as much as possible)willbe collected.These samples willbe flash-frozenin liquidnitrogen and storedin a freezer,setto maintain-60 to -80'C, untilshipped forpossible futureanalysisto: Kris J.Hansen, PhD 3M E. T. & S. Bldg. 2-3E-09 935 Bush Avenue St.Paul,Minnesota 55106 Telephone No.: 651.778.6018 FacsimileNo.: 651.778.6176. Kfis J.Hansen or her alternatewillbe notifiedregardingthe shipment of the sauples. EffectiveApril 6,2000 12. Page 3, Regulatory Compliance. To includea coniplianceexception forthe fecalanalysisdone atthe Mayo Clinic,deletethe textin thissectionand replace with thefollowing. This studywillbe conducted in compliance with theEnvironmental Protection Agency Good Laboratory PracticeRegulationsas setforthinTitle40 of the US Code of Federal Regulations,Part792, issuedNovember 29, 1983 (effective December 29, 1983),and with any applicableamendments with the following exception.Analysis of fecalsamples forurobilinogenat theMayo Clinicwillnot be done in compliance with GLPS. 326 Covance 6329-223 3M T-6295.7 ProtocolAmendincat No. 3 page 5 13. Page 3,Quality Assurance. To includean exception forthe fecalanalysisdone attheMayo Clinic,add thefollowingtotheend of thesection. Analysisof fecalsamplesforurobilinogeanttheMayo Clinicwillnotbe done in compliancewith GLPs and willnotbe auditedby a QualityAssuranceUnit. 14. Page 12, Additional Fecal Samplm To clarifyanalysisand reporting requirementsforfecalanalysisa,dd thefollowingtotheend ofthissection. The sampleswillbe analyzedforurobilinogenusinga routinestandardized colorrnetriacssay.The resultosftheseanalyseswillbe providedforinclusioinn thefmal report. 15. Page 17,Record Retendoi4 Paragraph 2. To includetherecordretention requirementsforfecalanalysisd,eletethisparagraphand replacewiththe following. Within Iyearaftersubmissionof thefmal report,alloftheaforementioned materialsfrom theSponsoes designees(AniLyticsInc.,3M E. T. & S,Mayo Clinic,and PathologyAssociateIsnternationawli)llbe senttotheSponsor (Andrew Seacat,PhD, 3M) by theSponsor'sdesignees. EffectiveApr*d 7,2000 16. Page 2,Purpose. To modifythepurposeof thestudy,deletethetextinthis sectionand replacewiththefollowing. To assesstheeffectofthetestmaterialon criticaelnzyme levelsh,ormones,and otherselectedbiochemicalparameterswhen administereddailyby capsuleto cynomolgus monkeys foratleast26 weeks. The treatmentperiodwillbe followedby an approximate52-week recoveryperiod. 327 ANTNDNYM APPROVAL Covance 6329-223 3M T-6295.7 PrOtOcOlAmcndment No. 3 Page 6 Andrew M. Seacat,PhD Study Monitor 3M PeterJ.Thomford, PhD Study Dhvctor Covance Laboratones Inc. Date Date 329 - ----- ---- APPENDIX 2 IndividuaAlnhnd FateData IndividuaCllinicaOlbservations individuaolphthalmicObservations Covance 6329-223 3M T-6295.7. 329 APPENDIX 2 individual Animal Pate Data 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULFONIC ACID POTASSIUM SALT (PPOST-6295) IN CYNOMOLGUS MONKEYS ------------ --------------------------------------------------------------------------------------------------- ANIMAL NUMBER ------ 105508 105517 105519 105520 105526 105527 105514 105515 105516 105521 105505 105510 105518 105523 105524 105528 105506 105507 IOSS09 105511 105512 105522 105529 105530 105531 105535 105544 105549 105537 105541 105547 105550 105532 105538 DOSE GROUP ----- 1 1 1 1 1 1 2 2 2 2 3 3 3 3 3 3 4 4 4 4 4 4 1 1 1 1 1 1 2 2 2 2 3 3 SEX ------ MALE MALE MALE MALE MALE MALE MALE MALE MALE HALE MALE MALE 14ALE MALE MALE MALE KALE MALE MALE MALE MALE MALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE DEATH CODE ----- T T T 0 0 T T T T T 6 T T 6 T T m T D u T u p T T T T p T T T, T T T TYPE OF DEATH ----------- SCHEDULED SCHEDULED SCHEDULED UNSCHEDULED UNSCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED UNSCHEDULED SCHEDULED UNSCHEDULED SCHEDULED SCHEDULED SCHEDULED UNSCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED UNSCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED DESCRIPTION OF DEATH ------------------------- TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE UNSCHEDULED DEATH UNSCHEDULED DEATH TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE SIXTH INTERIM SACRIFICE TERMINAL TERMINAL SACRIFICE SACRIFICE SIXTH INTERIM SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE UNSCHEDULED DEATH TERMINAL SACRIFICE UNSCHEDULED DEATH FIRST POST-RECOV SAC TERMINAL SACRIFICE FIRST POST-RECOV SAC UNSCHEDULED DEATH TERMINAL TERMINAL SACRIFICE SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE UNSCHEDULED DEATH TERMINAL TERMINAL TERMINAL SACRIFICE SACRIFICE SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE DATE OF DEATH -------- 02/25/99 02/25/99 02/25/99 02/25/00 02/25/00 02/25/99 02/25/99 02/26/99 02/26/99 02/26/99 03/08/00 02/26/99 02/26/99 03/08/00 02/26/99 02/26/99 02/20/99 02/25/99 01/27/99 02/25/00 02/25/99 02/25/00 02/25/00 02/25/99 02/26/99 02/26/99 02/25/99 02/25/00 02/25/99 02/26/99 02/26/99 02/26/99 02/25/99 02/25/99 DAY OF STUDY - ----- 184 184 184 549 549 184 184 185 185 185 561 185 185 561 185 185 179 184 iss 549 184 549 549 184 185 185 led 549 184 185 18S 185 184 184 WEEK 0 STUDY ------ 27 27 27 79 79 27 27 27 27 27 al 27 27 81 27 27 26 27 23 79 27 79 79 27 27 27 27 79 27 27 27 27 27 27 330 APPENDIX 2 Individual Animal Fate Data 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------ ------------ ------------------------------------------------------------------------------------------ AN114AL NUMBER ------ 105539 105S45 105548 105552 105533 105534 105536 105540 105542 105551 DOSE GROUP ----- 3 3 3 3 4 4 4 4 4 4 SEX ------ FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE DEATH CODE ----- 6 T T 6 u T T T u T TYPE OF DEATH ----------- SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED DESCRIPTION OF DEATH ------------------------- SIXTH INTERIM SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE SIXTH INTERIM SACRIFICE FIRST POST-RECOV SAC TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE FIRST POST-RECOV SAC TERMINAL SACRIFICE DATE OF DEATH -------- 03/08/00 02/25/99 02/25/99 03/08/00 02/25/00 02/26/99 02/25/99 02/26/99 02/25/00 02/26/99 DAY OF STUDY ------- 561 184 184 561 549 185 184 185 549 185 WEEK STUU ----- el 27 27 al 79 27 27 27 79 27 331 Appendix 2 individual Clinical observations Treatment 26-NEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNONOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: NI DOSE: 0 NG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSE AM OBS UNSCHED 30-90 OB DISPATCH 105508 T 27 NORMAL NO REMARKABLE OBSERVATIONS p p 15 p 22 p 29 p 36 p 43 p 50 p 57 p 64 p 71 p 78 p 85 p 92 p 99 p 106 p 113 p 120 p 127 p - - - 134 p - - - 141 p - - - 148 p - - - 155 p - - - 162 p - - - 169 p - - - 176 p - - - 183 P - - - 184 p - - p 332 Appendix 2 Individual Clinical.Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: MI DOSE: DAYS 1-195 0 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERVJ AN OHS UNSCHED 30-90 OB DISPATCH 105517 T 27 NORMAL NO REMARKABLE OBSERVATIONS QUALITATIVE LOW FOOD CONSUMPTION 1 p 8 p is p - - - 22 p - - - 29 p - - - 36 p - - - 43 p - - - 50 p - - 57 p - - 64 p - - 7*1 p 78 p - - 85 p - - 92 p - - 99 p - - 106 p - - 113 p - - 120 p - - 127 p - - 134 p - - 141 p - - 148 p - - 155 p - - 162 p - - 169 p - - 176 p - - 183 P - - 184 p - - p 102 p 333 Appendix 2 individual Clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: Ml DOSE: 0 MG/KG/DAY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH GUALIP IER DAYS 1-185 DAY ' (CONTINUED FROM PREVIOUS PAGE) 105517 T 27 QUALITATIVE FOOD CONSUMPTION L-OW 141 176 177 179 'C' - COMMENTS LISTED AT END OF OBS AM OBS UNSCHED 30-90 08 DISPATC p - - - p - - - p - - - p - - - 105519 T 27 NORMAL NO REMARKABLE OBSERVATIONS 1 8 p is p 22 p - 29 p - 36 p - 43 p - 50 p - 57 p - 64 p - 71 p - 78 p - 85 p - 92 p - 99 p - - - 106 p - - - 113 p - - - 120 p - - - 127 p - - - 134 P - - - 141 p - - - 148 p 155 p 162 p 169 p 334 Appendix 2 individual clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS -M-O-N-KE-Y-S----------------- --------------------------------- ---------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Mi DOSE: 0 MG/KG/DAY DAYS 1-185 DAY C. - COMMENTS LISTED AT END OF OBSERV, AN OBS UNSCHED 30-90 OR DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105519 T 27 NORMAL NO REMARKABLE OBSERVATIONS 176 p 183 p 184 p p 105520 0 79 DISCHARGE VOMITUS CONTAINING FOOD EXCRETION LIQUID FECES NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 141 p 29 p @29 p p 1 p a p is p - - - - - - 22 p - - - 36 p - - - 43 p p - - - 5570 p - - - 64 p - - - 71 p - - - 78 p - 85 p 92 p 99 p 106 p 113 p 120 p 127 p 335 Appendix 2 individual Clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH pERpLUOROOCTME SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------- ----------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Ml DOSE: DAYS 1-185 0 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSE AN OBS UNSCRED 30-90 08 DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105520 0 79 NORMAL NO REMARKABLE OBSERVATIONS 134 p 148 p - - - 155 p - - - 162 p - - - 169 p 176 p - - - 183 p - - - 105526 0 QUALITATIVE LOW FOOD CONSUMPTICN 79 EXCRETION NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 122 p - - - 179 p - - - 1 p - - - 8 p 15 p 22 p 29 p - - - 36 0 43 p - - 50 p - - 57 p - - 64 p 71 P 78 p 85 p 92 p 99 p 106 p 336 Appendix 2 individual Clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH . CATEGORY KEYWORD QUABIFIER GROUP: Ml DOSET 0 MG/KG/DAY DAYS 1-185 DAY -c, - COMMENTS LISTED AT END OF OBSERV AN OHS EMSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105526 0 79 NORMAL NO REMARKABLE OBSERVATIONS 113 p 120 p - 127 p - 134 p - 141 p - 140 p - 155 p - 162 P - 169 p - 176 p - 183 p - 105527 T 27 DISCHARGE UNKNOWN SOURCE FOUND IN PAN RED IN COLOR 144 p - EXCRETION NON-FORMED FECES SKIN & PELAGE BROKEN SKIN HAND-LEFT TAIL 2 p - 37 p - 38 p - p 39 p p 40 p - 43 P - 168 - - p 169 p - 170 - - p 176 p - 177 - - p 337 Appendix 2 Individual Clinical.observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CY-N-OM-O-L-GU-S- -M-O-NK-E-Y-S-------------------- ------------------------------------;-------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: MI DOSE: 0 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSE AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105527 T 27 SKIN & PELAGE BROKEN SKIN TAIL TAIL-DISTAL 178 p p 179 p 180 p 181 - - p 183 p 184 p 145 p p NORMAL NO REMARKABLE OBSERVATIONS 1 p 8 p is p - - - 22 p - - - 29 p 36 p - - - so p - - - 57 p - - - 64 p 71 p 78 p es p - - - 92 p - - - 99 p -- -- -- 110163 pP - - - 120 p - 127 p - 134 p - 141 p - 148 p 338 Appendix 2 individual Clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOL9.US MONKEYS ---------------------------------------------------------------------------------- ----------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: Ml DAYS DOSE: 1-185 0 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERV, AN OBS UNSCHED 30-90 08 DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105527 T 27 NORMAL NO REMARKABLE OBSERVATIONS 155 p 162 p QUALITATIVE LOW FOOD CONSUMPTION 43 p 339 Appendix 2 individual clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUPT M2 DAYS DOSE: 1-185 0.03 MG/KG/DAY DAY IC, - COMMENTS LISTED AT END OF OBSERVJ AN OBS UNSCHED 30-90 OB DISPATCH 105514 T 27 EXCRETION LIQUID FECES NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 91 p 105 132 - - p - p 1 p - 8 p 15 p - 22 p - 29 p -- - - 36 p 43 p - - - so p - - - 57 p - - - 64 p 71 p - - - 78 p - - - 85 p - - - 92 p - - - 99 p -- -- -- 106 p - - - 113 p 120 p - - - 127 p - - - 134 p - - - 141 p - - - 148 p - - - iss p 162 p -- -- -- 169 p - - - 176 p 340 Appendix 2 individual Clinical <)bservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SUT.FONIC ACID POTASSIUM SALT (PFOS;T-6295) IN,CYNOMOLOGUS MONKEYS -------- ------------------------------------------------------------------------------------------------------ ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: M2 DAYS DOSET 1-185 0.03 MG/KG/DAY DAY C. _ C0141IMS LISTED AT END OF OBSERVA AM OBS UNSCHED 30-90 08 DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105514 T 27 NORMAL NO REMARKABLE OBSERVATIONS 193 p 184 p p QUALITATIVE LOW FOOD CONSUMPTION 102 p 179 p 105515 T 27 EXCRETION NON-FORMED FECES NCIRKHL NO REMARKABLE OBSERVATIONS 69 p 1 p 8 p 15 p - - - 22 p -- -- -- 29 p - - - 36 p 43 p - - - 50 p - - - 57 p - - - 64 p - - - 71 p - - - 78 p -- -- -- 85 p - - - 92 p 99 p - - - 106 p - - - 113 p - - - 120 p - - - 127 p - - - 134 p - - - 341 Appendix 2 individual Clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY 'Cl - COMMENTS LISTED AT END OF OBSERVJ AN OBS UNSCHED 30-90 OR DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105515 T 27 NORMAL NO REMARKABLE OBSERVATIONS 141 p 148 p 155 p 162 p 169 p 176 p 1I8B3S pp p QUALITATIVE LOW FOOD CONSUMPTION 141 p - 162 p - 105516 T 27 DISCHARGE VOMITUS CONTAINING FOOD PARTIAL CAPSULE NORMAL NO REMARKABLE OBSERVATIONS 179 p - 05 - - p 1 p - 8 p 15 p - - 22 p - - 29 p - - 3436 pP - - - 50 p - - - - - - 5674 ppp -- -- -- 71 78 p - - - 342 Appendix 2 individual Clinical-Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULFORIC AciD POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------- -------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH. CATEGORY KEYWORD QUALIFIER GROUP: M2 DAYS DOSE: 1-185 0.03 MG/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBS AN OBS UNSCHED 30-90 OB DISPATCI (CONTINUED FROM PREVIOUS PAGE) 105516 T 27 NORMAL NO REMARKABLE OBSERVATIONS 85 p - 92 p - 99 p - 106 p - 113 p - 120 p 127 p 134 p 141 p - 148 p - 155 p - 162 p - 169 p - 176 p - 183 p - 185 p - p 105521 T QUALITATIVE LOW FOOD CONSUMPTION 27 SKIN & PELAGE BROKEN SKIN PERI-ORBITAL-RIGHT NORMAL No REMARKABLE OBSERVATIONS 179 p - 20 p - p I p 8 p is p 22 p 29 p 36 p 343 Appendix 2 Individual Clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTA?IE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOHOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M2 DOSE: 0.03 HG/KG/DAY DAYS 1-185 DAY IC, - COMMENTS LISTED AT END OF OBSE AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105521 T 27 NORMAL NO REMARKABLE OBSERVATIONS 43 p -- -- -- 50 p - - - 57 p 64 p - - - 71 p - - - 78 p - - - 85 p - - - 92 p - - - 99 p - - - 106 p - - - 113 p - - - 120 p - - - 127 p - - - 134 p - - - 141 p - - - 146 p - - - 155 p 162 p - - - 169 p - - - 176 p - - - 183 p - - - iss p p 344 Appendix 2 individual Clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP. M3 DOSE: 0.15 MG/KG/DAY DAYS 1-18S DAY -c, - COMMENTS LISTED AT END OF OBSERVI AN OBS UNSCHED 30-90 OB DISPATCH IOS505 6 81 DISCHARGE VOMITUS CONTAINING FOOD NORMAL NO REMARKABLE OBSERVATIONS 141 p I p 8 p 15 p 22 p - - - 29 p - - - 36 p - - - 43 p - - - 50 p 57 p - - - - - - 64 p - - - 71 p - - - 78 p - - - 85 p - - - 92 p - - - 99 p 106 p - - - 113 p - 120 p - 127 p - 134 p - its p 155 p 162 p 169 p 176 p 183 p 345 Appendix 2 individual Clinical-observations Treatment 2 6-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH .CATEGORY KEYWORD ()UALIFIER GROUP: M3 DAYS DOSE: 1-185 0.15 MG/KG/DhY DAY 'C' - COMMENTS LISTED AT END OF OBSERV AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS 105505 6 el PAGE) QUALITATIVE LOW FOOD CONSUMPTION 80 P 141 p 180 p 105510 T 27 EXCRETION DISCOLORED URINE RED IN COLOR NORMAL NO REMARKABLE OBSERVATIONS 97 p 1 p 8 p is p 22 p 29 p 36 p 43 p 50 p 57 p - - - 64 p - - - 71 p - - - 78 p - - - 85 p - - - 92 p - - - 99 p - - - 106 p - - - 113 p - - 120 p - - 134 p - 141 p 346 Appendix 2 individual Clinical.observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC I ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLOUS MONKEYS --------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M3 DOSE: DAYS 1-185 0.15 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERVJ AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105510 T 27 NORMAL NO REMARKABLE OBSERVATIONS 155 p - - - 162 p - - - 169 p - - - 176 p - - - 183 p - - - 185 p - - p QUALITATIVE LOW FOOD CONSUMPTION 67 p - - - 73 p - - - 109 p - - - 127 p - - - 141 p - - - 142 p - - - 148 p - - - - - - 154 p - - - 180 p 183 p - - - 105518 T 27 DISCHARGE VOMITUS CONTAINING FOOD NORMAL NO REMARKABLE OBSERVATIONS 179 p - - - 1 p - - - 8 p 15 p - - - 22 p - - - 29 p 36 p - - - 43 p - - - 347 Appendix 2 individual Clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT JPFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP- M3 DOSE: DAYS 1-185 O.lS MG/KG/DAY DAY (CONTINUED FROM PREVIOUS PAGE) 105518 T 27 NORMAL NO REMARKABLE OBSERVATIONS 50 57 64 71 78 85 92 99 106 113 120 127 134 141 148 155 162 169 176 183 185 QUALITATIVE FOOD CONSUMPTION LOW 141 179 'C' - COMMENTS LISTED AT END OF OBSE AN OBS UNSCHED 30-90 08 DISPATCH p - - - p - - - p - - - p - - - p - - - p - - - p - - - p - - - p - - - p - p p p p p p - - - p - - - p - - - p - - - p - - - p - - p p - - p - - 348 Appendix 2 individual Clinical.observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANI14AL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERV) AM OBS UNSCHED 30-90 OB DISPATCH 105523 6 81 SKIN & PELAGE BROKEN SKIN TAIL NORMAL NO REMARKABLE oBsERvATrONS 149 p 1 p 8 p is p 22 p - - - 29 p - - - 36 p - - - 43 p - - - 50 p - - - 57 p - - - 64 p - - - 71 p - - - 78 p - - - as p 92 p - - - 99 p - - - 106 p - - - 113 p - - - 120 p - - - 127 p - - - 134 p - - - 141 p - - - 148 p - - - 155 p - - - 162 p - - - 169 p - - - 176 p - - - 183 p - - 349 Appendix 2 individual Clinical 4Dbservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD ()UALIFIER GROUP: H3 DAYS DOSE: 1-195 0.15 MG/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBSERVJ AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105523 6 el QUALITATIVE LOW FOOD CONSUMPTION 6 p 141 p 179 p 105524 T 27 DISCHARGE VOMITUS CONTAINING FOOD EXCRETION NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 141 p 179 p iso p 1 p 8 p 15 p - - 22 p - - 29 p - - 36 p - - 50 p - - - 57 p - - - 64 p - - - 71 p - - - 78 p - - - as p - - - 92 p - - - 99 p - - - 106 p - - - 113 p - - - 350 Appendix 2 individual.Clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------- ------------------------------------------------------------------------- i ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M3@ DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERV) AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105524 T 27 MORKAL NO REMARKABLE OBSERVATIONS 120 p 127 p 134 p 140 p 155 p 162 p 169 p - - 176 p - - 183 p - - 185 p - - p QUALITATIVE LOW FOOD CONSUMPTION 43 p - - 65 p - - 141 p 179 p iso p 105528 T 27 NORMAL NO REMARKABLE OBSERVATIONS I p p 15 p 22 p 29 p 36 p 43 p 50 p 57 p 64 p 71 p 05 p 351 Appendix 2 individual Clinical.Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAN]3 SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M3 DAYS DOSE: 1-185 0.15 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERVJ AN OHS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105528 T 27 NORMAL NO REMARKABLE OBSERVATIONS 92 p - - - 99 p - - - 106 p - - - 120 p -- -- -- 134 p - - - 141 p 148 p - - - 155 p - - - 162 p - - - 169 p - - - 176 p - - 183 p - - 185 p - - p QUALITATIVE LOW FOOD CONSUMPTION 78 p - - - 113 p - - - 116 p - - - 127 p - - - 134 p - - - 162 p - 176 p - 179 p - 352 Appendix 2 individual Clinical-Observations Treatment 26-WEEK CAPSULE TOXI CITY STUDY WITH PERFLUOROOCTAWE SULFONIC ACID POTASSIUM SALT (PFOS;T76295) IN cyNot4OLGUS MONKEYS --------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M4 DOSE: DAYS 1-185 0.75 MG/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBSERVJ AN OBS UNSCHED 30-90 OB DISPATCH 105506 m 26 BEHAVIOR ATAXIC <UNSPECIFIED> HYPOACTIVE <UNSPECIFIED> DISCHARGE EXCESSIVE SALIVATION RESPIRATION LABORED NORMAL NO REMARKABLE OBSERVATIONS 179 - p - p 179 - p - p 179 - p - 179 - p - p 1 p 8 p is p - - 22 p - - 29 p - - 36 p - - 43 p -- -- 5570 pp - - 64 p - - 71 p - - 78 p - - 85 p 92 p - - 99 p - - 106 p - - 113 p - - 120 p - - 127 p - - 353 Appendix 2 individual Clinical.Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS -M-O-N-KE-Y-S-------------------------- ---------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M4 DOSE: DAYS 1-185 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERV, AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105506 m 26 NORMAL NO REMARKABLE OBSERVATIONS 134 p -- -- -- 141 p - - - 148 p 155 p - - - 162 p - - - 169 p - - - 176 p QUALITATIVE LOW FOOD CONSUMPTION 3 p - - - 141 p 178 p 179 p 105507 T 27 DISCHARGE VOMITUS PARTIAL CAPSULE SKIN & PELAGE BROKEN SKIN DIGIT(S)-FRONT-LEFT 11 ill 178 p p p - 97 p - 98 p - p - 99 p - p - 100 p - 101 - - p 102 p 104 p p 106 p p 107 p p 354 Appendix 2 Individual ClinicalObservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOUIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSER% A14 OBS UNSCHED 30-90 08 DISPATCH (CONTINUED 105507 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE BROKEN SKIN DIGIT(S)-FRONT-LEFT 108 p ill - - p 112 p p NORMAL NO REMARKABLE OBSERVATIONS 1 p 8 p 15 p - - - 22 p - - - 29 p - - - 36 p - - - 43 p - - - so p - - - 57 p - - - 6-1 p - - - 71 p - - - 78 p - - - 85 p - - - 92 p - - - 113 p - - - 120 p - - - 127 p - - - 134 p - - 141 p - - - 148 p - - - 155 P - - - 162 p - - - 169 p - - 176 p - - 103 p - - 355 Appendix 2 individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFTUOROOCTAME SUTFONIC ACID POTASSIUM SALT IPFOS;T-6295) IN CYNONOWUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSE AN OBS UNSCHED 30-90 08 DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105507 T 27 NORMAL NO REMARKABLE OBSERVATIONS 184 p p QUALITATIVE LOW FOOD CONSUMPTION 141 p 105509 D 23 APPEARANCE APPEARS DEHYDRATED OTHER 155 - p p 155 - PC BEHAVIOR HYPOACTIVE <UNSPECIFIED> 155 - p p EXCRETION DISCOLORED BLACK IN FEW FECES FECES COLOR LIQUID FECES MUCOID FECES NO FECES 155 p 152 p 155 p 155 p 155 p 154 p - - - - - - - - - - - - - - - - - - EYES CONSTRICTED EYES RESPIRATION LABORED PUPIL lS4 - p - 155 p p 356 Appendix 2 individual Clinical pbservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOHOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP.- MA DAYS DOSE: 1-195 0.75 MG/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBSERV@ AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS 105509 D 23 PAGE) SKIN & PELAGE COLD TO TOUCH BODY-ENTIRE PALE SKIN GUMS 155 p p 154 p 155 p p NORMAL NO REMARKABLE OBSERVATIONS 1 p a p is p - - - 22 p - - - 29 p - - - 36 p 43 p - - - 50 p - - - 57 p - - - 6& p 71 p 78 p as p 92 p - - 99 p - - 106 p - - 113 p - - 120 p - - 127 p - - 134 p - - 141 p - 148 p - 357 Appendix 2 individual ClinicalObservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYN M LGUS MONKEYS -------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: M4 DAYS DOSE: 1-185 0.75 MG/KG/DhY DAY 'C' - COMMENTS LISTED AT END OF OBSERV AM ORS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS 105509 D 23 PAGE) QUALITATIVE L90W FOOD CONSUMPTION 141 p 152 p 154 p 155 p - 105511 U 79 DISCHARGE VOMITUS CONTAINING FOOD PARTIAL CAPSULE NORMAL NO REMARKABLE OBSERVATIONS 100 p - 155 - - p 1 p - 8 p 15 p 22 p - 29 p - 36 p - - - 43 p - - - 50 p - - - 57 p - - - 64 p - - - 71 p - - 78 p - - 85 P - - 92 p - - 99 p - - 106 p - - 113 p - - 120 p - - 358 Appendix 2 Individual clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC AciD POTASSIUM SALT (PFOSIT-6295) IN CYNOWOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: W4 DAYS DOSE: 1-185 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERVA' A@ OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAR.E) X05511 u 79 NORMAL NO REMARKABLE OBSERVATIONS 127 p - - - 134 p - - - 141 p - - - 148 p - - - 155 p - - - 162 p - - - 169 p - - - 176 p - - - 183 p QUALITATIVE LOW FOOD CONSUMPTION 57 p - - - 60 p - - - 100 p - - - 102 p - - - 141 p - - - 145 p - - - 148 p 154 p - - 155 p - - - 170 p - - - 171 p - - - 172 p - - - 173 p - - - 174 p - - - 175 p - - - 176 p - - - 177 p - - - 179 P - - - 180 p - - - 359 Appendix 2 Individual Clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT MM OF OBSERVJI AM OBS UNSCHED 30-90 OR DISPATCH 105512 T 27 DISCHARGE VOMITUS .PARTIAL CAPSULE EXCRETION FEW FECES NO FECES NON-FORKED FECES 32 - - p 37 - - p 100 p - - - 102 p - - - 105 p - - - 106 p - - - 110 p - - 125 p - - 126 p - - 127 p - - 128 p - - 129 p - - 130 p - - - 133 p - - - 134 p - - - 155 p - - - 156 p - - - 157 p - - - ,158 p 159 p - - - 161 p - - - 181 p - - - 183 p - - - 184 p - - - 99 p - - - 131 p - - - 132 p - - - 130 p - - - 360 Appendix 2 individual Clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPOWIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD C)UALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVJ AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105512 T 27 EXCRETION NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS OUALITATIVE LOW FOOD CONSUMPTION 133 p 1 p 8 p 15 p - - - 22 p - - - 29 p - - - 36 p - - - 43 p - - - 50 p - - - 57 p - - - 64 p - - - 71 p - - - 78 p - - - es p - - - 92 p - - - 113 p - - - 120 p - - - 141 p - - - 148 p - - - 162 p - - - 169 p - - - 176 p - - - 184 - p 17 p - - - 96 p - - - 99 p - - - 100 p - - - 361 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M4 DOSE: DAYS 1-185 (CONTINUED FROM PREVIOUS PAGE) 105512 T 27 QUALITATIVE LOW FOOD CONSUMPTION 0.75 MG/KG/DAY DAY 102 105 110 116 125 126 127 128 129 130 131 132 133 134 155 156 157 158 159 160 161 162 164 168 174 175 176 178 179 iso 181 .'C' - COMMENTS LISTED AT END OF OBSERVA AM OBS UNSCHED 30-90 OB DISPATCH p - p - - p - - p - - - p - - - p - - - p - - - p - - - p - p - p - p - p - p - p - P - p - p p p p p p p p p p p p p p 362 Appendix 2 Individual Clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFCNIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COHN M S LISTED AT END OF OBSERVA AN OHS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105512 T 27 QUALITATIVE LOW FOOD CONSUMPTION 183 p 105522 U 79 EXCRETION MUCOID FECES 179 p NORMAL NO REMARKABLE OBSERVATIONS I p 8 p is p 22 p - - 29 p - - 36 p - - 43 p - - 50 p - - 57 p - - 64 p - - - 71 p - - - 78 p - - - 85 p - - - 92 p - - - 99 p - - - 106 p - - - 113 p - - - 120 p - - - 127 p - - - 134 p - - - 141 p - - - 148 p - - - 155 p - - 162 p - - 169 p - 363 Appendix 2 individual Clinical4observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFOUIC ACID POTASSIUM SALT IPFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP. M4 DOSE: DAYS 1-185 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERVA AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105522 U 79 NORMAL NO REMARKABLE OBSERVATIONS 176 p - - - 183 p - - - QUALITATIVE LOW FOOD CONSUMPTION 102 p - - - 180 p - - - 364 Appendix 2 individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS_MCNKEYS -------- ------------------------------------------------------------------------------------------------------ CATEGORY ANIMAL GROUP STUDY DAY WK KEYWORD QUALIFIER FREE-TEXT COMMENT ----------------------------------------------------------------------------------------------------------------- 105509 M4 155 23 APPEARANCE OTHER AFTER DOSING ANIMAL BECAME RECUMBENT. ANIMAL DIED PRIOR TO VET EXAM. VET IWX' 365 Appendix 2 individual Clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC AciD POTASSIUM SALT IPFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSE: DAYS 1-185 0 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERVAT AM OBS UNSCHED 30-90 OB DISPATCH 105529 p 79 APPEARANCE APPEARS DEHYDRATED BEHAVIOR HYPOACTIVE <UNSPECIFIED> DISCHARGE NASAL CLEAR ORAL CLOUDY EXCESSIVE SALIVATION EXCRETION LIQUID FECES 5 6 p 7 p 6 7 p 8 p 5 6 p 7 p 8 p 9 p 6 7 p p 5 6 p 7 p 8 p 29 p 30 p 38 p 39 p p p p p p p p p p - - - p - 366 Appendix 2 individual Clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWE SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSE: 0 MG/KG/DAY DAYS 1-185 DAY c, - COMMENTS LISTED AT END OF OBSERV) AN OBS UNSCHED 30-90 OR DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105529 p 79 EXCRETION LIQUID FECES NON-FORMED FECES 40 p 41 p 42 p - p 43 p - 44 p - 65 - - p 66 P - - - 67 p 68 p - - - 69 p - - - 70 p - - - 91900 -p -- pp -- 101 p - 102 p - 115 - - p 71 p - 73 p - 77 p - 103 p - 115 p - SKIN & PELAGE ALOPECIA FEET 105 p - p - - p - 106 p 107 p - p - 108 p - p - 109 p - p - 110 p - p - ill p p 367 Appendix 2 individual Clinic&14Dbservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH pERpLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS -------------------------------------------------------------------------------------------------------7------- ANI14AL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD ()UALIFIER GROUP: Fl DOSE: 0 MG/KG/DAY DAYS 1-185 DAY -C- - CC)MMMS LISTED AT END OF OBSERV AM OBS UNSCHED 30-90 OB nispATCH (CONTINUED FROM PREVIOUS PAGE) iOSS29 p 79 SKIN & PELAGE ALOPECIA FEET 112 p p 113 p p 114 p p 115 p - p 117 p - p lie p p 119 p - p 120 p - p 121 p - p 122 - - p 124 - - p 125 p - p 126 p - p 127 p - p 128 p - p 129 - - p 130 p - p 131 p - p 132 p - p 133 p - p 134 p - p 135 p - p 136 p - p 137 p - p 138 P - 139 p - p 140 p - p 142 p - p 143 p - p 146 p - p 368 Appendix 2 individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------- -------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: PI DOSEs 0 MG/KG/DAY DAYS 1-185 DAY *C' - COMMENTS LISTED AT END OF OBSERVJ AN OHS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105529 p 79 SKIN & PELAGE ALOPECIA FEET 147 p - p 148 p - 1i4s9o pp -- pp - 115512 pp -- pp -- 153 p - p - 154 p - 155 p - 156 p - 157 p - p ise - p - p p - 162 - p - 163 p 164 p - p - 116656 pp -- pp -- 167 p - p - 168 p - p p - 169 p 170 p - p - - p - 171 p 172 p - p - 117734 pp -- pp -- 175 P - p - - p - 176 p 177 p - p - 178 p - p - 179 p - p - 369 Appendix 2 individual Clinical4Dbservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNONOLGOS MONKEYS -------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DAYS DOSE: 1-185 0 MG/KG/DAY DAY -C, - COMMENTS LISTED AT END OF OBSERVA AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED 105529 P FROM PREVIOUS PAGE) 79 SKIN & PELAGE ALOPECIA FEET LIMBS-HIND TAIL iso p p 181 - - p 182 p p 183 p - p 184 p - 185 p - 92 - - p - p - 93 - 94 p - p - 95 p - p - - p - 9968 pp - p - 99 p - p - 100 p - p - 101 p - 102 p - p 142 - - p 144 - - p 134 p - p 135 p - p 136 p - p 137 p - p 138 p 139 p 140 P 142 p 143 p 146 p 147 p p - p - p - p - p - p - 148 p 370 Appendix 2 individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SUPWIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------- -------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD C)UALIFIER GROUP: Fl DAYS DOSE: 1-185 0 MG/KG/DAY DAY -C, - COMMENTS LISTED AT END OF OBSERV, AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105529 p 79 SKIN & PELAGE ALOPECIA TAIL 149 p - p 150 p - p 151 p - p 152 p - p 153 p - p 154 p - iss p 156 p 157 p - p - p - 158 162 p p - 163 p - p - 164 p - p p - 16S p 166 p - p - 167 p - p 168 p p 169 p - p 170 p - p 171 p - p 172 p - p 173 p - p 174 p - p 175 p - p 176 p p- 177 p p - 178 p 179 p p p - - ISO p p - 181 p 371 Appendix 2 individual Clinical.observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOR.GUS MONKEYS ------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: PI DOSE: DAYS 1-185 0 MG/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBSERV AM OBS UNSCRED 30-90 OB DISPATCH (CONTINUED 105529 P FROM PREVIOUS PAGE) 79 SKIN & PELAGE ALOPECIA TAIL 182 p - p 163 p - p 184 p - 185 p - NORMAL NO REMARKABLE OBSERVATIONS QUALITATIVE LOW FOOD CONSUMPTION 1 p - 15 p - 22 p - 36 p - 50 p - 57 p - 64 p 78 p 85 p 92 p 141 p 5 p 8 p 41 p 42 p - 69 p - 72 p - 73 p - 75 p - 102 p - 174 p - 179 p 372 Appendix 2 Individual Clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNO14OLGUS MONKEYS ------- ------------------------------------------------------------------------------------------------------ ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DosE: DAYS 1-185 0 MG/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBSERV, AM OBS UNSCHED 30-90 OB DISPATCH 105530 T 27 DISCHARGE VOMITUS PARTIAL CAPSULE APPEARS TO BE MENSTRUATING EXCRETION DISCOLORED FECES RED IN COLOR LIQUID FECES MUCOID FECES NON-FORMED FECES 97 - p 39 - p 40 p 92 p 176 p 180 p 28 p 27 p 28 p - p 29 p - 31 - - p 32 p - 33 p - 34 p - p 35 p - 7 36 p - - 37 p - 30 p - p 39 - p 40 p - 49 p - 50 p - 51 p - p 55 p - 28 p - 12 p - 31 p 373 Appendix 2 individdal Clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAM SULPMIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANI14AL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: PI DOSE: 0 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSE AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105530 T 27 EXCRETION NON-FORMED FECES 41 p 54 p - 55 p - 57 p - SKIN & PELAGE BROKEN SKIN MOUTH 10 - - p 12 p - 15 p 22 p - 23 p - 25 p - p - 26 p - p - 27 p - p - 28 p - p - 29 p - p - 30 p - p - 31 p - p - NORMAL NO RE14ARKABLE OBSERVATIONS I p - 8 p 43 p 64 p 71 p 78 p 85 p 99 p 106 p 113 p 374 Appendix 2 individual Clinical Dbaervation's Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWE SULFOWIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYWOMOLGUS MONKEYS -------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSE: DAYS 1-185 0 MG/KG/DAY DAY IC, - COMM M S LISTED AT END OF OBSERV AN OBS UWSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105530 T 27 NORMAL NO REMARKABLE OBSERVATIONS 120 p - 127 p - 134 p - 141 p - 148 p - 155 p - 162 p - 169 p - 183 p - 184 p - - p QUALITATIVE LOW FOOD CONSUMPTION 26 p - - - 27 p - - - 29 p - - - 141 P. - - - 105531 T 27 DISCHARGE VOMITUS CONTAINING FOOD APPEARS TO BE MENSTRUATING NORMAL NO REMARKABLE OBSERVATIONS 179 p - - - 176 p - - - 1 p - - 8 p 15 p - - - 2229 pp - - - 36 p - - - 43 p - - - 50 p - - - 375 Appendix 2 individual Clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------ ------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSE: 0 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSE AM OBS UNSCHED 30-90 OB DISPATC (CONTINUED FROM PREVIOUS PAGE) 105531 T 27 NORMAL NO REMARKABLE OBSERVATIONS 57 p 64 p 71 p 78 p 85 p 92 p 99 p 106 p 113 p 120 p 127 p 134 p 141 p 148 p 155 p 162 p 169 p 183 p 185 p - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - p QUALITATIVE LOW FOOD CONSUMPTION 141 p 179 p 376 Appendix 2 individual Clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KETMRD ()UALIFIER GROUP: Fl DAYS DOSET 1-185 0 MGIKG/DAY DAY *C' - COMMENTS LISTED AT MM OF OBSE AN OBS UNSCHED 30-90 OB DISPATCH 105535 T 27 DISCHARGE APPEARS TO BE MENSTRUATING SKIN PELAGE RED SKIN LIMB-FRONT-RIGHT SCAB(S) LIMB-FRONT-LEPT LI14B-FRONT-RIGHT NORMAL NO REMARKABLE OBSERVATIONS 37 p 38 p - 108 p - p 137 p - p 113686 pp -- p - 167 p - p - 22 - - p - 23 - - p - 24 p - p - 193 p - 22 - - p 23 - - p 24 p - p I p - 8 p - - - 15 p - - - 22 p 29 p - - - 36 p - - - 43 P - - - so p - - - 57 p - - - 64 p - - - 71 p - - 377 Appendix 2 individual clinical4observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSEs DAYS 1-185 0 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERVJ AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105535 T 27 NORMAL NO REMARKABLE OBSERVATIONS 78 p - - - 85 p - - - - - 9929 pp -- -- -- 106 p 113 p - - 120 p - - - 127 p - - - 134 p 141 p - - - ide p 155 p 162 p 169 p 176 p 185 p - p 105544 T 27 DISCHARGE VOMITUS CONTAINING FOOD PARTIAL CAPSULE 141 p - - p - 29 - - p - 33 - - p - 34 66 - - p - 117 - - p - 141 - - p - DISCHARGE UNKNOWN FOUND IN PAN RED IN COLOR SOURCE 112 p - 378 Appendix 2 individual Clinical Dbaervations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ------ -------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSE: 0 MG/KG/DAY DAYS 1-185 DAY *Cl - COMMENTS LISTED AT END OF OBSERN AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS 105544 T 27 PAGE) NORMAL No REMARKABLE OBSERVATIONS 1 p 8 p p 22 p 29 p 50 p 57 p 64 p 71 p 78 p 85 p 92 p 99 p 106 p 113 p 120 p 134 p 148 p 155 p 162 p 169 p 176 p 183 p 184 p - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - - - - p QUALITATIVE LOW FOOD CONSUMPTICN 6 p 36 p 38 p 379 Appendix 2 Individual clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) I-N--C-Y-N-OM-O-L-GU-S---M-O-N-KE-Y-S------------------- ------- -------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: Pl DAYS DOSE: 1-185 0 MG/KG/DAY DAY c, - COMMENTS LISTED AT END OF OBSERV, AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105544 T 27 QUALITATIVE LOW FOOD CONSUMPTION 42 p - - - 43 p - - - 127 p - - - 171 p ild p 176 p 105549 P 79 DISCHARGE VOMITUS INTACT CAPSULE PARTIAL CAPSULE APPEARS TO BE MENSTRUATING SKIN & PELAGE BROKEN SKIN HEAD-CRANIAL PERI-ORBITAL-LEFT 97 175 p 3 7 8 p is p p p p p p - p NORMAL NO REMARKABLE OBSERVATIONS 1 p - 22 p - 29 p - - - 36 p - - - 43 p 50 p - - - 57 p - - - 64 p - - - - - 71 p 78 p 380 Appendix 2 individual Clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULPONIC' ACID POTASSIUM SALT JPFOS;T-6295) IN CYNOMOLGUS MONKEYS ------- ------------------------------------------------------------ -------------------------------------- ANI14AL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSE: DAYS 1-185 0 MG/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OEISERV AN OHS UNSCRED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105549 P 79 NORMAL NO REMARKABLE OBSERVATIONS p 92 p 99 p 106 p 113 p 120 p 127 p 134 p 141 p 148 p iss p 162 p 169 p 176 p 183 p - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - QUALITATIVE LOW FOOD CONSUMPTION 141 p - - - 175 p - - - 381 Appendix 2 individual ClinicalObservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------ ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERV) AM OBS UNSCHED 30-90 OB DISPATCH 105537 T 27 DISCHARGE VOMITUS WHITE IN COLOR APPEARS TO BE MENSTRUATING SKIN & PELAGE BROKEN SKIN HEAD-K"ILLARY-RIGHT PERI-ORBITAL-LEFT PGRI-ORBITAL-RIGHT 1 - p 45 - - p 46 - - p 47 p - 48 p - - p - 49 - p - 72 p 73 p - p - *Y4 p - p - 7S p - 104 p - 105 p - p 106 p - p 107 p 168 p - p 169 p - p 50 - - p 52 - - p 8 p - p 9 p p 10 p p 3 p p 4 p 6 p p 7 p 382 Appendix 2 individual Clinical-Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS -------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F2 DAYS DOSE: 1-185 0.03 MG/KG/DAY DAY 'C' - C01414ENTS LISTED AT END OF OBSERVJ AM OBS uNscHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS 105537 T 27 PAGE) NORMAL NO REMARKABLE OBSERVATIONS I p - - 15 p - - 22 p - - 29 p - - 36 p - - 43 p - - so p - - 57 p - - 64 p - - - 71 p - - - 78 p - - - 85 p - - - 92 p - - - 99 p 113 p 120 p 127 p 134 p - - - - - - - - - - - - 141 p 148 p - - - 155 p - - - 162 p - - - 176 p - - - 183 p - - - 184 p - - p 383 Appendix 2 individual Clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F2 DAYS DOSE: 1-185 0.03 NO/KG/DAY DAY -C, - COMMENTS LISTED AT END OF OBSERV AM oss UNSCHED 30-90 OB DISPATCH 105541 T 27 DISCHARGE APPEARS TO BE MENSTRUATING EXCRETION FEW FECES SKIN & PELAGE BROKEN SKIN PERI-ORBITAL-RIGHT NORMAL NO REMARKABLE OBSERVATIONS 99 p 102 p 152 - p 154 - p 141 p 98 p 99 p p 102 p 1 p 0 p 15 p 36 p - - - 5570 pp - - - 64 p -- -- -- 71 p - - - 78 p 85 p - - - 92 P - - - 106 p - - - 120 p - - 127 p - - 134 p - - 148 p 384 Appendix 2 Individual Clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH pERpLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOSiT-6295) IN CYNOMOLOUS MONKEYS -------------------------------------------- ---------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY. KEYWORD QUALIFIER GROUP: F2 DAYS DOSE: 1-185 0.03 MG/KG/DAY DAY *C' - COMMENTS LISTED AT END OF OBSERV AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105541 T 2'7 NORMAL NO REMARKABLE OBSERVATIONS 155 p - 162 p - 169 p - 176 p - 183 p - 185 p p QUALITATIVE LOW FOOD CONSUMPTION 3 p 22 p - 28 p - 29 p - 43 p - 55 p - 57 p - 76 p - 87 p - 113 p - 140 p - 169 p - 174 p - 179 p - 105S47 T 27 DISCHARGE APPEARS TO BE MENSTRUATING 129 p - 164 - - p 165 P - 167 p - EXCRETION FEW FECES 150 p 385 Appendix 2 individual Clinical*observations Treatment 26-WEEK CAPSULE TOXICITY ACID POTASSIUM SALT ------------------------------------------------------------------------ STUDY WITH PERFLUOROOCTANE (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: P2 DAYS DOSE: 1-185 0.03 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERV AN OHS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105547 T 27 EXCRETION FEW FECES NO FECES NON-FORMED FECES 151 p - - 152 p - - 156 p - - - 168 p 154 p - - - 155 p - - - 178 p - - - 181 p SKIN & PELAGE BROKEN SKIN HEAD-MAXILLARY-LEFT SCAB(S) HEAD-MAXILLARY-LEFT 170 p - p - - p - 171 p 172 p - p - 173 - - p - 174 p - p - 175 p - 176 p - 178 p - p NORMAL NO REMARKABLE OBSERVATIONS 1 p - 8 p - - - 15 p - - - 22 p 29 p - - - 36 p - - - 50 p 57 p - - 64 p - - - 386 Appendix 2 individual Clinical.observations Treatm6nt 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: P2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT OW OF OBSERVJ AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105547 T 27 NORMAL NO REMARKABLE OBSERVATIONS 71 p - - - 78 p 85 p - - - 92 p - - - 106 p - - - 113 p - - - 134 p - - - 141 p 148 p 162 p 169 p 183 p 195 p - - p QUALITATIVE LOW FOOD CONSUMPTION 17 p - - 41 p - - 43 p - - 55 p - 57 p - - 6969 pp - - - 120 p - - - 121 p - - - 127 p - - - 134 P - - - 141 p - - - 148 p - - - 150 p - - - 151 p - - - 152 p - - 387 Appendix 2 individual Clinical.observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSE AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105547 T 27 QUALITATIVE LOW FOOD CONSUMPTION 154 p - 155 p - 156 p - - 160 p -- -- -- 161 p - - - 162 p 165 p - - - 167 p - - - 168 p - - - 169 p - - 170 p - - 171 p - - 174 p - - 175 p - - 179 p - - 184 p - - 105550 T 21 DISCHARGE APPEARS TO BE MENSTRUATING 91 - - p 92 p - NORMAL NO REMARKABLE OBSERVATIONS 1 p - 8 p 15 p - 22 p - 29 P - 36 p - - - 43 p - - - 50 p - - - 57 p - - - 388 Appendix 2 individual Clinical.Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULFONIC ACID POTASSIUM SALT (PFOS:T-6295) IN CYNOMOLGUS MONKEYS -------------------------------------------------------------------7---------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F2 DOSE: DAYS 1-185 0.03 MG/KG/DAY DAY IC, - COMMENTS LISTED AT END OF OBSE AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105550 T 27 NORMAL NO REMARKABLE OBSERVATIONS 64 p - - - 71 p - - - - - 78 p - - - 85 p 99 p - - - 106 p -- -- -- 113 p - - - 120 p 127 p - - - 134 p - - I&I p 148 p 155 p 162 p - - 169 p - - 176 p - - 183 p 185 p - - p QUALITATIVE Low FOOD CONSUMPTION 3 p - 141 p - 179 p - 389 Appendix 2 individual clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH VERFLUOROOCTANE SULFMIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------ ------------------------------------------------------------------------------------------------------ ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD C)UALIFIER GROUP: F3 DOSE: DAYS 1-185 0.15 MG/KG/DAY DAY 'C* - COMMENTS LISTED AT END OF OBS AN OBS UNSCHED 30-90 OB DISPATC 105532 T 27 SKIN & PELAGE BROKEN SKIN HEAD-CRANIAL PERI-ORBITAL-RIGHT NORMAL NO REMARKABLE OBSERVATIONS 2 p - p - 3 p - p - 31 - - p - 32 p - p - 33 p - 1 p a p - - - 15 p 22 p - - - 36 p - - - 43 p - - - 50 p - - - 57 p - - - 64 p -- -- -- 7912 pp - - - 99 p - - - 106 p - - - 113 p - - 127 p - - - 134 p - - - 141 p - - - 148 p - - - 155 p - - - 162 p - - - 169 p - - - 176 p - - - 183 p - - - 390 Appendix 2 Individual Clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ------- ------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE . WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: F3 DAYS DOSE: 1-185 0.15 MG/KG/DAY DAY C. - COMMENTS LISTED AT END OF OBSEE AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105532 T 27 NORMAL NO REMARKABLE OBSERVATIONS QUALITATIVE LOW FOOD CONSUMPTION 184 p - - p 26 p - - - 29 p - - - 32 p - - - - - 41 p - - - 55 p - - - 57 p so p 65 p - - - 78 p - - - 85 p - - - 115 p - - - 116 p - - - 120 p 126 p - - - 141 p - - - - - 143 p - - - 147 p ISO p - - - 155 p - - - 162 p 164 p - - - 169 p - - - 170 p - - - - - - 174 p - - - 175 p - - - 176 p - - - 179 p 183 p - - - 391 Appendix 2 Individual Clinical.Observations Treatment 26-WEEK CAPSUIE TOXICITY STUDY WITH PERFLUOROOCTANE SLM170HIC ACID POTASSIUM SALT (PFOSIT-6295@ IN CYHOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD ()UALIFIER GROUP- P3 DAYS DOSE: 1-185 0.15 MG/KG/DAY DAY 'C' - CON24ENTS LISTED AT END OF OBSE AN OBS UNSCHED 30-90 OB DISPATC 105538 T 27 DISCHARGE VOMITUS CONTAINING FOOD EXCRETION FEW FECES NOR14AL NO REMARKABLE OBSERVATIONS 141 p - - - 179 p - - - 43 p - - - I p - - - ap - - - 15 p - - - 22 p 29 p - - - 36 p - - - 50 p - - - 57 p - - - 64 p - - - 71 p - - - 78 p - - - 85 p - - - 92 p - 99 p - 106 p - 113 p - 120 p - - - 127 p - - - 134 P - - - 148 p - - - 155 p - - - 162 p - - - 169 p - - - 392 Appendix 2 individual Clinicil-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- AN114AL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F3 DAYS DosE: 1-185 0.15 MG/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBSERV, AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105538 T 27 NORMAL NO REMARKABLE OBSERVATIONS 176 p - - 183 p - - 184 p - - p QUALITATIVE LOW FOOD CONSUMPTION 27 p - - - 41 p - - - 42 p - - - 43 p - - - 141 p - - - 160 p - - - 167 p - - - 174 p - 178 p - 179 p - 105539 6 81 DISCHARGE APPEARS TO BE MENSTRUATING EXCRETION FEW FECES NORMAL NO REMARKABLE OBSERVATIONS 71 p - p 141 p - 1 p - a p 15 p - - - 22 p - - - 29 p - - - 36 p - - - 43 p - - - 50 p - - - 393 Appendix 2 individual Clinical4Dbservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------- ------------------------------------------------------------------------------------------------------ ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F3 DAYS DOSE: 1-185 0.15 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT MM OF OSSMTV) AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105539 6 91 NORMAL NO REMARKABLE OBSERVATIONS 57 p 64 p 78 p 92 p 99 p 106 p 120 p 134 p 148 p 155 p 162 p 169 p 176 p 103 p - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - QUALITATIVE LOW FOOD CONSUMPTION 17 p is p 24 p - - - 57 p - - - 60 p - - - 70 p - - - 85 p - - - 109 p - - - - - 113 p - - - 116 p - - - 127 p 132 p - - - 133 p - - - 138 p - - - 139 p - - - 394 Appendix 2 individual Clinical.Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------- ------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: P3 DAYS DOSE: 1-185 0.15 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERV@ AN OHS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105539 6 81 QUALITATIVE LOW FOOD CONSUMPTION 150 p - - - 155 p - - - - - 158 p 159 p - - - 162 p -- -- 171 p 174 p - - 179 p - - 105545 T 27 DISCHARGE APPEARS TO BE MENSTRUATING EXCRETION NO FECES NORMAL NO REMARKABLE OBSERVATIONS 136 p - p 51 p - 1 p - 8 p is p - - - 22 p - - - 29 p - - - 36 p - - - 50 p - - 57 p 64 p - - -- 71 p - - - es p - - - 92 p 99 p - - - 106 p - - - 127 p - - - 395 Appendix 2 individual Clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOI#OLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANI14AL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F3 DAYS DOSE: 1-185 0.15 NO/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBSERV) AN OBS uNscHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105545 T 27 NORMAL NO REMARKABLE OBSERVATIONS 134 p 141 p - - - 148 p 155 p - - - 162 p - - - 176 p - - - 183 p - - - 184 p p ()UALITATIVE LOW FOOD CONSUMPTION 25 p 30 p 35 p - - 43 p - - 74 p - - - 78 p - - - 86 p - - - 113 p - - - 116 p - - 120 p - 141 p - 149 p - - - 150 p - - - 155 p - - - 161 p - - - 169 p - - - 171 p - - - 174 p - - - 175 p - - - 176 p - - - 179 p - - - 396 Appendix 2 Individual Clinical,observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------- -------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F3 DAYS DOSE: 1-185 0.15 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERV AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105545 T 27 QUALITATIVE LOW FOOD CONSUMPTION 180 p 183 p 105548 T 27 DISCHARGE VOMITUS CONTAINING FOOD EXCRETION FEW FECES NORMAL NO REMARKABLE OBSERVATIONS 141 p 178 p 1 p 8 p is p 22 p 29 p - - 36 p 43 p - - so p - - 57 p - - 64 p - - 71 p - - 78 p - - 85 p - - - 92 p 99 p - - - 106 P - - - 113 p - - - 120 p - - 112374 pp - - - 397 Appendix 2 individual Clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFIM'C ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F3 DAYS DOSE: 1-185 0.15 MG/KG/DAY DAY c, - COMMENTS LISTED AT END OF OBSERV AM OBS UNSCHED 30-90 08 DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105548 T 27 NORMAL NO REMARKABLE OBSERVATIONS 148 p -- -- -- 116525 pp - - - 169 p - - - 176 p - - - 183 p - - - 184 p - - p QUALITATIVE LOW FOOD CONSUMPTION 18 p - - 28 p - - se p 141 p 142 p 174 p 105552 6 81 NORMAL NO REMARKABLE OBSERVATIONS 1 p 8 p 15 p - 22 p - 29 p - - 36 p - - 43 p - - 50 p - - 57 p - - 64 p -- - - 71 p 78 p - - - 85 p - - 92 p - - - 398 Appendix 2 individual Clinical.observations Treatment 26-WEEX CAPSULE TOXICITY STUDY WITH pERpLuOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS -- ---------------------- --------------- --------------------------------------------------------------------7-- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: P3 DAYS DOSE: 1-185 0.15 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT EM OF OBSERVA AN OHS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105552 6 81 NORMAL NO REMARKABLE OBSERVATIONS 99 p 106 p 113 p 120 p 127 p 134 p 141 p 148 p 155 p 162 p 169 p 176 p 183 p - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - QUALITATIVE LOW FOOD CONSUMPTION 20 p - 141 p - 156 p - 399 Appendix 2 individual Clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOXGUS MONXEYS --------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DAYS DOSE: 1-185 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERVI AN OBS UJNSCHED 30-90 OB DISPATCH 105533 u 79 DISCHARGE APPEARS TO BE MENSTRUATING SKIN & PELAGE ALOPECIA HEAD-CRANIAL 39 p - p 40 p - 22 - - p - 24 - - p - 27 p - p - 28 - - p - 29 p - p - - p - 30 p 31 p - p - 32 p - p - 33 - - p - - p - 34 p 35 p - p - 36 p - p 37 - - p 38 p - p 39 p - p 40 p - 41 p - p - 42 p - p - 43 p - p - 44 - - p - 45 - - p - 48 - - p 49 - - p 50 p - p 51 p - p 52 p - p 400 Appendix 2 individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD ()UALIFIER GROUP: F4 DOSET DAYS 1-195 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSE AN OBS UNSCHBD 30-90 OB DISPATCH (CONTINUED 105533 U FROM PREVIOUS PAGE) 79 SKIN & PELAGE ALOPECIA HEAD-CRANIAL HEAD-MAXILLARY-LEFT 53 p p - 54 p p - 55 p - p - 56 p - p - 57 p - p - 58 p - p - 59 p - p - 60 - - p - 61 - - p - 62 p - 27 - - p 28 - - p - 29 p p - 30 p - p - 31 p - p - 32 p - p - 33 - - p - 34 p - p - 35 p - p - 36 p - p - 37 - - p - 38 p - p - 39 p - p - 40 p - 41 p - p 42 p - p - 43 p - p - 44 - - p - 45 - - p - 48 - - p - 401 Appendix 2 individual Clinical@observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD C)UALIFIER GROUP: F4 DAYS DOSE: 1-185 0.75 MG/KG/Dhy DAY 'C' - COMMENTS LISTED AT END OF OBSERVN AM OBS uNscHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PACE) 105533 u 79 SKIN & PELAGE ALOPECIA HEAD-MAXILLARY-LEFT HEAD-MAXILLARY-RIGHT 49 p 50 p - p 51 p - p 52 p - p 53 p - p 54 p - p 55 p - p 56 p - p - 57 p - p - 58 p - p - 59 p - p - 60 - - p - 61 - - p - 62 p - p 63 p - p - 27 - p - 28 - p - - p - 2390 pp - p - 31 p - p - 32 p - p - 33 - - p - 34 p - p - 35 p - p - 36 p - p - 37 - - p - 38 p - p - 39 p - p - 40 p - 41 p p 402 Appendix 2 individual Clinical.observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGus MONKEYS -------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP- F4 DOSE: DAYS 1-185 0.75 HO/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBSERV@ AN OBS uNscHED 30-90 OB DISPATCH (CONTINUED 105533 U FROM PREVIOUS PAGE) 79 SKIN & PELAGE ALOPECIA HEAD-MAXILLARY-RIGHT 42 p p - 43 p - p - 44 - - p - 45 - - p - 48 - - p - 49 - - p - 50 p - p - 51 p - p - 52 p - p - 53 p - p - 54 p - p - 55 p - p - 5567 pp - pp - 58 p - p - 59 p - p - 60 - p - 61 p 62 p p 63 p p NORMAL No REMARKABLE OBSERVATIONS 1 p 8 p is p - 22 p - 64 p - 71 p - 78 p - es p 403 Appendix 2 individual Clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------- --------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DOSE: DAYS 1-185 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT OF OBSERVA AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105533 u 79 NORMAL NO REMARKABLE OBSERVATIONS 92 p - - - 99 p -- -- -- 106 p - - - 113 p 120 p - - - 127 p - - - 134 p - - - 141 p 148 p - - 155 p - - - 162 p - - - 169 p - - - 176 p - - - 183 p - - - 105534 T QUALITATIVE LOW FOOD CONSUMPTION 27 DISCHARGE VOMITUS PARTIAL CAPSULE APPEARS TO BE MENSTRUATING 141 p - - - 6 - - p 10 - - p 72 - - p 59 p - 99 p - 133 p - 134 p - EXCRETION DISCOLORED FRCES RED IN COLOR 149 p - 404 Appendix 2 individual Clinical.Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT IPFOS;T-6295) IN CYNOMOEGUS MONKEYS --------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DAYS DOSE: 1-185 0.75 MG/KG/DAY DAY IC, - COMMENTS LISTED AT END OF OBSERVJ AM OBS UNSCRED 30-90 OB DISPATCH (CONTINUED 105534 T FROM PREVIOUS PAGE) 27 EXCRETION DISCOLORED RED IN YELLOW FEW FECES FECES COLOR IN COLOR LIQUID FECES MUCOID FECES NO FECES NON-FORMED FECES 150 p - - - 156 p - - - 102 p - - - 105 p - - - 107 p - - - 109 p - - - 113 p - - - 127 p - - - 163 p - - - 92 p - - - 93 p - - - 136 p - - - 137 p - p - 138 p - 139 p - 141 p - p 142 p - - - 143 p - - - 144 p - - - 156 p - - - 185 p - - - iso p - - - 49 P. - - 110 p - - 113 P - - 127 p - - 137 p - - 140 p - - 144 p - - 145 p - - 405 jkppendix 2 individual Clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFORIC ACID POTASSIUM SALT IPFOS;T-6295) IN CYNOMOLGUS MONKEYS ------- -------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Pt DAYS DOSE: 1-185 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT MM OF OBSERVA AN OBS LINSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105534 T 27 EXCRETION NON-FORMED FECES 146 p - - - 147 p - - - 148 p - - - 149 p - - - 150 p - - - SKIN & PELAGE BROKEN SKIN PERI-ORBITAL-LEF"r OTHER 70 71 p 9 PC 10 PC - 12 PC - 15 PC - p - p - PC - PC - PC NORMAL NO REMARKABLE OBSERVATIONS 1 p - 29 p - 36 p - 50 p - 57 p - 64 p - 85 p - 99 p - 106 p - 155 p - 162 p - 169 p - 176 p - 183 p - iss p 406 Appendix 2 individual clinical.Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOIOOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER (CONTINUED FROM PREVIOUS 105534 T 27 PAGE) GROUP: F4 DOSE: DAYS 1-185 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OHS AN OBS UNSCHED 30-90 OB DISPATC QUALITATIVE LOW FOOD CONSUMPTION 2 p 3 p 8 p 10 p - - - 22 p - - - 24 p - - - 30 p - - - 43 p - - - 49 p - - - 60 p - - - 63 p - - - 66 p - - - 78 p - - - so p - - - el p 92 p 93 p 98 p 100 p 102 p - 105 p - 109 p - 113 p - 116 p - 120 p - 122 p - 125 p - 127 p - 128 p - 407 Appendix 2 individual Clinical-Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DOSE:.0.75 DAYS 1-185 MG/KG/DAY DAY 'C* - COMMENTS LISTED AT END OF OBSE AN OBS UNSCHED 30-90 OB DISPATCI (CONTINUED FROM PREVIOUS PAGE) 105534 T 27 QUALITATIVE LOW FOOD CONSUMPTION 129 p - - - 133 p - - - 134 p - - - 137 p - - - 138 p - - - 141 p - - - 148 p - - - 149 p - - - 150 p - - - 154 p - - - 155 p - - - 156 p - 157 p - - - 162 p - - - 164 p - - - 167 p - - - 170 p - - - 174 p - - - 175 p - - 176 p - - 180 p - - 184 p - 105536 T 27 DISCHARGE VOMITUS CONTAINING FOOD PARTIAL CAPSULE EXCRETION DISCOLORED FECES RED IN COLOR 14 1 p - 30 - - p 69 - p 408 Appendix 2 Individual Clinical.Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY -C- - COMMMS LISTED AT END OF OBSERV AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED 105536 T FROM PREVIOUS PAGE) 27 EXCRETION FEW FECES LIQUID FECES NON-FORMED FECES p - - - Be p - - - 179 p - - - 183 p - - - NOR14AL NO REMARKABLE OBSERVATIONS 1 p - - - ap - - - 15 p - - - 22 p 29 p - - - 36 p - - - 43 p - - - 50 p - - - 57 p - - - 64 p - - - 71 p - - - 78 p - - - 85 p - - - 92 p - - - 99 p - - - 106 p - - - 113 p - - - 120 p - - - 134 p - - - 149 p 155 p - 162 p - 169 p - 176 p - 184 p - p 409 Appendix 2 individual Clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE qULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ------- ------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WX OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVP AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS 105536 T 27 PAGE) QUALITATIVE LOW FOOD CONSUMPTION 3 p 65 p 72 p al p Be p 114 p 117 p 126 p 127 p 129 p 130 p 141 p 149 p 156 p 157 p 160 p ISO p 181 p 105540 T 27 DISCHARGE VOMITUS INTACT CAPSULE EXCRETION DISCOLORED FECES RED IN COLOR DISCOLORED URINE GREEN IN COLOR 99 p 27 p p 28 p p 71 p 410 Appendix 2 individual Clinical.ObservationB Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOSsT-6295) IN-CYNOMOLGUS-MONKEYS ------------------- --------------------------------------------------------------------------------- ------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUATIFIER GROUPT F4 DAYS DOSE: 1-185 0.75 MG/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBSERVA! AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED 105540 T FROM PREVIOUS PAGE) 27 EXCRETION DISCOLORED GREEN IN FEW FECES URINE COLOR MUCOID FECES 72 p 28 p 29 p 28 - 29 p - p SKIN & PELAGE ALOPECIA DORSAL DORSAL-THORACIC 1 p 141 1 2 p 3 5 6 p 7 p 8 p 9 p 10 p 11 p 12 p 13 p 14 p 15 p 16 p 17 p 18 p 19 p 20 p 21 p p p p p p p p p p p p - p - p - p - p - p - p - p - p - p - p 411 Appendix 2 individual clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD ()UALIFIER GROUPT F4 DAYS Doss: 1-185 0.75 MG/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBSERVA AN OBS uNscHED 30-90 OB DISPATCH (CONTIMED FROM PREVIOUS PAGE) 105540 T 27 SKIN & PELAGE ALOPECIA DORSAL-THORACIC 22 p p 23 p p 24 p p 25 p - p 26 p - p 27 p - p 28 p - p 29 p - p 30 p - p 31 p - p 32 p - p 33 p - p 34 p - p 35 p - p 36 p - p 37 p - p 38 p - p 39 p - p 40 p - 41 p - p 42 p - p 43 p - p 44 - - p 45 - - p 46 P - p 47 p - p 48 - - p 49 - p 50 p p 51 p 412 Appendix 2 individual Clinical.observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD ()UALIFIER GROUP: P4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT MM OF OBSE AN OBS UNSCHED 30-90 OB DISPATC] (CONTINUED 105540 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE AT,OPECIA DORSAL-THORACIC 142 p - p - 143 p - p - 146 p - p - 147 p - p - 148 p - p 149 p - p 150 p - p 151 p p 152 p p 153 p p 154 p p 155 p - p - 156 p - p - 157 p - p - 158 p - p - 159 p - p - 160 p - p - 161 p - p - 162 p - p - 163 p - p - 164 p - p - 165 p - p - 166 p - p - 167 p - p - 168 p - p - 169 p - p - 170 p - p - 171 p - p - 172 p - p - 173 p - p - 413 Appendix 2 Individual Clinical.Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOEOGUS MONKEYS -------------------------------- ----------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: P4 DAYS DOSE: 1-185 0.75 MO/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERV AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED 105540 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE ALOPECIA DORSAL-THORACIC DORSAL-THORACIC-LEFT 174 p - p - 175 p - p - - p - 117776 pp - p - 178 p - p - 179 p - p - iso p - p - 181 p p 182 p - p 183 p - p 184 p - p 185 p - p 57 - -- pp -- 58 p 59 p - p - - 60 p 61 p p - p - 62 p - p - - p - 6643 pp - p - 65 p - p - 66 p - p - - p - 67 p 68 p - p - 69 p - p - 70 p - p - - p - 71 p 72 p - p - 73 p - p - 74 p - p - 414 Appendix 2 individual Clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANRKAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fd DOSE: 0.75 MG/KG/DAY DAYS 1-195 DAY 'C' - COMMENTS LISTED AT END OF OBSE AM OHS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105540 T 27 SKIN & PELAGE ALOPECIA DORSAL-THORACIC-LEFT 76 p - p 77 p - p 78 p - 79 p - p so p - p 81 p - p 82 p - p 83 p - p ot p p 85 p - p 86 p - p 87 p - p 88 p - 89 p - p 90 p - p 91 p - p 92 p - p 93 p - p 94 p - p 95 p - p 96 p - p 97 p - p 98 p - p 99 p - p 100 p - p 101 - - p - 102 p - p - 103 p - p - 104 p - p - 105 p - p - 415 Appendix 2 Individual Clinical,Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD- QUALIFIER GROUP: F4 DOSE: DAYS 1-185 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERV AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED 105540 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE ALOPECIA DORSAL-THORACIC-LEFT 106 p - p - 107 p - p - 108 p - p - 109 p - p - 110 p - p - ill p 112 p - p p - 113 p - p - 114 p - p - 115 p - p - 117 p - p - lis p p 119 p - p - 120 p - p - 121 p - p - 122 p - p - 123 p - p - 124 p - p - 125 p - p - 126 p - p - 127 p - p - 128 p - p - 129 - - p - 130 - - p - 131 - - p - 132 p - p - 133 p - p - 134 p - p - 135 p - p - 136 p - p - 416 Appendix 2 individual Clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNONOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY GROUP: F4 KEYWORD C)UALIFIER DAYS ------------- (CONTINUED FROM PREVIOUS PAGE) 105540 T 27 SKIN & PELAGE ALOPECIA DORSAL-THORACIC-LEFT DOSE: 1-185 HEAD-ENTIRE 0.75 MG/KG/DAY DAY 137 138 139 ito 1 2 3 5 6 7 a 9 10 11 12 13 14 15 16 17 is 19 20 21 22 .23 24 25 26 27 'C' - COMMENTS LISTED AT END OF OBSBR% AN ORS UNSCHED 30-90 OB DISPATCH p - p - p - p - p - p - p - p - p - p - p p p p p p p p p p p p p p p p p - p - p - p - p - p - p - p - p - p - p - p - p p p - p - p - p - p - p - p - p - p - p - p - p - p - p - p - p - p - p - 417 Appendix 2 individual Clinical*observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOUIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSE AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED 105540 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE ALOPECIA HEAD-ENTIRE LIMB-HIND-LEPT 28 p - p - 29 p - p - 30 p - p - 31 p - p - 32 p - p - 33 p - p - 34 p - p - 35 p - p - 36 p - p - 37 p - p - 38 p - p - 39 p - p - 40 p - 41 p - p - 57 - - p - 58 p - p - 59 p - p - 60 p - p - 61 p - p - 62 p - p - 63 p - p - 64 p - p - 65 p - p - 66 p - p - 67 P - p - 68 p - p 69 p - p - 70 p - p - 71 p - p - 72 p p - 418 Appendix 2 Individual clinical-Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: P4 DAYS DOSE: 1-185 0.75 MG/KG/DAY DAY -Cl - COMMENTS LISTED AT END OF OBSE AM OBS UNSCRED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105540 T 27 SKIN & PELAGE ALOPECIA LIMB-HIND-LEFT 73 p - p - 74 p - p - 76 p - p - 77 p - p - 78 p - 79 p - p 80 p - p - 81 p - p - 82 p - p - 83 p - p - 84 p - p - 85 p - p - 86 p - p - 87 p - p - so p - 89 p 90 p p p - 91 p - p - 92 p - p - 93 p - p - 94 p - p - 95 p - p - 96 p 97 p 98 p 99 p - p - p - p - p 100 p p 101 - - p 102 p p 103 p p 419 Appendix 2 individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULF@MIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------- ------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NU14BER CODE DEATH CATEGORY KEYWORD ()UALIFIER GROUP: F4 DAYS DOSE: 1-185 0.75 NGIKG/EkAY DAY 'C' - COMMENTS LISTED AT END OF OBSERVJ AN OHS UNSCHED 30-90 OB DISPATCH (CONTINUED 105540 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE ALOPECIA LIMB-HIND-LEFT LIMBS-ALL LIMBS-FRONT 104 p - 42 p - p 43 p - p 44 - p ts - p - p - 46 p 47 p - p - 48 - - p - 49 - - p - 50 p - p - 51 p p 52 p - p 53 p - p 54 p - p 55 p - p 56 p - 57 p - 1 p - p 2 p p 3 p 5 p 6 p p 7 p p 8 p p 9 p p 10 p p 11 p p 12 p p 13 p p 14 p p 420 Appendix 2 individual Clinical-Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) lw CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP- P4 DAYS DOSE: 1-185 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERVJ AN OHS UNSCHED 30-90 OB DISPATCH (CONTINUED 105540 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE ALOPECIA LIKBS-FRONT TAIL 15 p p 16 p p 17 p p is p p 19 p - p - 20 p - p - 21 p - p - 22 p - p - 23 p - p - 24 p - p - 25 p - p - 26 p - p - 27 p - p - 28 p - p - 29 p - p - 30 p - p - 31 p - p - 32 p - p - 33 p - p - 34 p - p - 35 p - p - 36 p - p - 37 p - p - 38 p - p - 39 P - p - 40 p - 41 p p 145 - - p 146 p p 147 p p 421 Appendix 2 individual Clinical.observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFOXIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOHOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DAYS DOSE: 1-185 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT EM OF OBSE AM OBS UNSCHED 30-90 08 DISPATO (CONTINUED 105540 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE ALOPECIA TAIL 148 p - p - 149 p - p - 150 p - p - 151 p - p - 152 p - p - 153 p - p - 154 p - p - 155 p - p - 156 p - p - 157 p p - 156 p p 159 p - p - 160 p - p - 161 p - p - 162 p - p - 163 p - p - 164 p - p - 165 p - p - 166 p - p - 167 p p - 168 p p - 169 p - p - 170 p - p - 171 p - p - 172 p - p - 173 p - p - 174 p - p - 175 p - p - 176 p - p - 177 p - p - 422 Appendix 2 individual Clinical-Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------ -------------------------------------------------------------------------------------------------------- ANIMAL NUKBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DOSE: 0.75 NO/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSE AN OBS UNSCHED 30-90 08 DISPATCH (CONTINUED 105540 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE ALOPECIA TAIL 178 p p 179 p p 180 p p 181 p p 182 p - p 183 p - p 184 p - p 185 p - - p QUALITATIVE LOW FOOD CONSUMPTION 17 p - - - 20 p - - - 25 p - - - 27 p - - - 69 p - - - 71 p - - - 73 p - - - 74 p - - - 78 p - - - so p - - - 85 p 87 p - 120 p - 132 p - 137 p - 141 p 155 p 179 p 423 Appendix 2 individual Clinical-Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD ()UALIFIER GROUPT F4 DAYS DOSE: 1-185 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERV, AN OBS UNSCHED 30-90 OB DISPATCH 105542 u 79 DISCHARGE VOMITUS INTACT CAPSULE PARTIAL CAPSULE APPEARS TO BE MENSTRUATING EXCRETION FEW FECES SKIN & PELAGE PALE SKIN HEAD-ENTIRE NORMAL NO REMARKABLE OBSERVATIONS 136 p - p - 65 - - p - 78 - - p - 126 - - p - 131 - - p - 71 p - p - 115 p - 161 p - iss p - 161 p - 162 p - 162 p 183 p 184 p 1 p 8 p is p 22 p 29 p so p 57 p 64 p - - - - - - - - - - - - - - - es p 424 Appendix 2 individual Clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNONOTGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DAYS DOSE: 1-185 0.75 MG/KG/DAY DAY C- - COMMENTS LISTED AT END OF OBSERVA AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105542 u 79 NORMAL NO REMARKABLE OBSERVATIONS 99 p - 106 p - 113 p - 120 p - 127 p - 134 p - 141 p - 148 p - 169 p - 176 p - QUALITATIVE LOW FOOD CONSUMPTION 14 p 36 p - 43 p - 49 p - 57 p - 59 p - 60 p - 65 p - 78 p - 92 p - 98 p - 125 p - 134 p - 139 p - 141 p - - - 142 p - - - 143 p - - - 154 p - - - 155 p - 425 Appendix 2 individual Clinical-Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWE SULFOWIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOL(;US MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DOSE: DAYS 1-185 0.75 MO/KG/DAY DAY *Cl - COMMENTS LISTED AT END OF OBSERV AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105542 u 79 QUALITATIVE LOW FOOD CONSUMPTION 161 p - 162 p - 175 p - 105551 T 27 DISCHARGE APPEARS TO BE MENSTRUATING 43 - - p - 44 - - p - 45 - - p - 73 p - p - 74 p - p - 75 p - p - 76 p - p - 80 p - 112 p - p - 113 p - p - 137 - - p - 138 p - p - 119 p - p - 140 p - p - 141 p - p - 166 p - p - 167 p - p - 168 p - EXCRETION FEW FECES SHALL FECES SKIN & PELAGE ALOPECIA LIMBS-ALL 161 P 49 p 1 p - - p - p 426 Appendix 2 Individual Clinical.observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERPLUOROOCTAME SULFMIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD ()UALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSE AN OHS UNSCHED 30-90 OB DISPATCH (CONTINUED 105551 T PROM PREVIOUS PAGE) 27 SKIN & PELAGE ALOPECIA LIMBS-ALL 2 p 3 4 5 6 p 7 p a p 9 p 10 p 11 p 12 p 13 p 14 p is p 16 p 17 p 18 p 19 p 20 p 21 p 22 p 23 p 24 p 25 p 26 p 27 p 28 p 29 p 30 p 31 p p p p p p p p p p p p p p p p p p p p - p - p - p - p - p - p - p - p - p - p - p 427 Appendix 2 individual Clinical-observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWE SULFONIC ACID POTASSIUM SALT (PPOS;T-629S) IN CYNOMOLGUS MONKEYS ------- -------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP:,F4 DAYS DOSE: 1-185 0.75 MG/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBSERVA AM OBS UNSCHRD 30-90 OB DISPATCH (CONTINUED 105551 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE ALOPECIA LIMBS-ALL 32 p - p - - p - 33 p 34 p - p - 35 p - p - 36 p - p - 37 p - p - 38 p - p - - p - 39 p 40 p - p - 4412 pp - pp - 43 p - p - 44 - - p - 45 - - p - 46 p - p - 47 p - p - 48 p - 49 p - p - 50 p - p - - p - 51 p 52 p - p - 53 p - p 54 p - p - 55 p - p - 56 p - p - 57 p - p - 59 p - p - 59 p - p - 60 p - p - 61 p - p - 428 Appendix 2 individual Clinical Dbservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKBYS -------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: P4 DOSE: DAYS 1-185 0.75 MG/KG/DAY DAY 'C' - COTMMS LISTED AT END OF OBSERVJ AM OHS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105551 T 27 SKIN & PELAGE ALOPECIA LIMBS-ALL 62 p - p 63 p - p - 64 p - p - 65 p - p - 66 p - p - 67 p - p - 68 p - p - 69 p - p - 70 p - p - 71 p - p - 72 p - p - 73 p - p - 74 p - p - 75 p - p - 76 p - p - 77 p - p - 78 p - p - 79 p - p - so p - p - 81 p - p - 82 p - p - 83 p - p - 84 p - p - 85 p - p - 86 P - p - 87 p - p - Be p p 89 p p 90 p p 91 p p 429 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DAYS DOSET 1-185 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERV AN OBS UNSCHED 30-90 OB DISPAT( (CONTINUED 105551 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE ALOPECIA LIMBS-ALL 92 p - p - 93 p - p - 94 p - p - 95 p - p - 96 p - p - 97 p - p - 98 p - p - 99 p - p - 100 p - p - 101 - - p - 102 p - p - 103 p - p - 104 p - p - 105 p - p - 106 p - p - 107 p - p - 108 p - p - 109 p - p - 110 p - p - ill p p 112 p - p - 113 p - p - 114 p - p - 115 p - p - 116 - - p - 117 p - p - lie p - p - 119 p - p - 120 p - p - 121 p p - 430- Appendix 2 individual ClinicaliDbaervations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER'CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERV AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED 105551 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE ALOPECIA LIMBS-ALL 122 p - p - 123 p - p - 124 p - p - 125 p - p - 126 p - p - 127 p p - 128 p p - 129 - - p - 130 - - p - 131 - - p - 132 p - p - 133 p - p - 134 p - p - 135 p - p - 136 p - p - 137 p - p - 138 p - p - 139 p - p - 140 p - p - 141 - - p - 142 p - p 143 p - p 144 - - p 145 - - p 146 P - p 147 p - p 148 p - p 149 p - p 150 p - p 151 p p 431 Appendix 2 individual Clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD ()UALIFIER GROUP: Ft DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY IC, - COMMENTS LISTED AT END OF OBSERVA AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED 105551 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE ALOPECIA LIMBS-ALL 152 p - p - 153 p - p - 154 p - p - 155 p - p - 156 p - p - 157 p - p - 158 p - p - 159 p - p 160 p - p 161 p - p 162 p - p 163 p - p 164 p - p 165 p - p 166 p - p 167 p - p - 169 p - p - 169 p - p - 170 p - p - 171 p - p - 172 p - p - 173 p p - 174 p - p - 175 p - p - 176 P - p - 177 p - p - 178 p - p - 179 p - p - iso p - p 181 p p 432 Appendix 2 Individual Clinicalobservations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTME SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fd DAYS DOSE: 1-185 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERV, AM OBS UNSCHED 30-90 08 DISPATCH (CONTINUED 105551 T FROM PREVIOUS PAGE) 27 SKIN & PELAGE ALOPECIA LIMBS-ALL 182 p - p 183 p - p 184 p - p 185 p - - p ()UALITATIVE FOOD CONSUMPTION LOW 72 p - - 85 p - - 102 p - - 146 p 162 p 433 Appendix 2 individual clinical observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- CATEGORY STUDY KEYWORD FREE-TFXT COMMENT A-N-I-M-AL----G-RO-U-P----DA-Y--W-K--------QU-A-L-IF-I-E-R ----------------------------------------------------------------------------- 105534 P4 92 TO 15 3 SKIN & PELAGE OTHER BRUISED SKIN PERI-ORBITAL LEFT EYE. 434 Appendix 2 individual Clinical.observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------- ------------------------------------------------------------------------------------------------------ ANIMAL DEATH NU14BER CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP.- Ml DAYS DOSE: 186-365 0 NO/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBSERVJ AN OHS UNSCHED 30-90 OB DISPATCH 105520 0 79 SKIN & PELAGE BROKEN SKIN DIGIT(S)-FRONT-LEFT NORMAL No REMARKABLE OBSERVATIONS 361 p - - 362 p - - - 190 p - - - 197 p - - - 204 p - - - 211 p - - - 218 p - - 225 p - - - 232 p - - - 239 p - - - - - 246 p 253 p 260 p - - 267 p - - 274 p - - 281 p - - 288 p -- - - 295 p - - - 302 p 309 p - - - 316 p -- -- -- 332330 pp - - - 337 p -- -- -- 344 p - - 351 p 358 p - 365 p - 435 Appendix 2 individual Clinical observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MOHK13YS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP.- Ml DOSE: 0 MG/KG/DAY DAYS 186-365 DAY 'C' - COMMENTS LISTED AT END OF OBSERVI AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS 105520 0 79 PAGE) QUALITATIVE LOW FOOD CONSUMPTION 105526 0 79 NOR14AL NO REMARKABLE OBSERVATIONS 273 p 190 p 197 p 204 p - - - 211 p - - - 218 p - - - 225 p 232 p - - - 239 p - - - 246 p - - - 253 p - - - 260 p - - - 267 p - - - 274 p - - - 281 p 288 p - - - 295 p -- -- -- 302 p - - - 309 p 316 p - - - 323 p - - - 330 p - - - 337 p - - - 344 p - - - 351 p - - - 358 p 365 p - - - 436 Appendix 2 individual Clinicalobservations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SU@FONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS -------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M3 DAYS Doss: 186-365 0.15 MG/KG/DAY DAY -C- - COM4ENTS LISTED AT END OF OBSERVA AM OBS UNSCHED 30-90 08 DISPATCH I0550S 6 81 EXCRETION NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 191 p - - - 190 p - - - 197 p -- -- -- 204 p 211 p - - - 218 p 225 p 232 p 239 p 246 p 253 p 260 p - - - 267 p - - - 274 p - - - 281 p - - - 288 p - - - 295 p - - - 302 p -- -- -- 309 p 316 p - - - 323 p - - - 330 p -- -- -- 337 p - - - 344 p 351 p - - - 358 p - - - 365 p - - 437 Appendix 2 Individual Clinical-observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOWIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYWOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M3 DOSE: 0.15 MG/YG/DAY DAYS 186-365 DAY C. - COMMENTS LISTED AT EM OF OBSERV, AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS 105505 6 el PAGE) QUALITATIVE LOW FOOD CONSUMPTION 105523 6 81 NORMAL NO REMARKABLE OBSERVATIONS 240 p - - - 190 p - - - 197 p - - - 204 p - - - 211 p - - - 218 p - - - 225 p 232 p - - - 239 p - - - 246 p - - - 253 p - - - 260 p - - - 267 p - - - 274 p 281 p 299 p 295 p 302 p 309 p 316 p 323 p 330 p 337 p 344 p 351 p 358 p 365 p 438 Appendix 2 individual Clinical.observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------- -------------------------------------------------- ------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M3 DAYS DOSE: 186-365 0.15 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERVI AN OHS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS 105523 6 81 PAGE) QUALITATIVE LOW FOOD CONSUMPTION 247 p 439 Appendix 2 Individual Clinicalobservations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTARE SULFONIC ATID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M4 DAYS DOSE: 186-365 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSE AN OBS UNSCHED 30-90 OB DISPATC 105511 U 79 NORMAL NO REMARKABLE 013StRVATIONS QUALITATIVE LOW FOOD CONSUMPTION 190 p 197 p - - 204 p - - 211 p - - 218 p - - 225 p - - 232 p - - 239 p - - 246 p - - 253 p - - 260 p - - 267 p - - 274 p - - 281 p - - 288 p - - 295 . P - - 302 p - - 309 p - - 316 p - - 323 p - - 330 p - - 337 p - - 344 p - - 351 p - - 358 p - - 365 p - - 255 p - - 440 Appendix 2 individual Clinical-Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M4 DAYS DOSE.- 0.75 186-365 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSE AM OHS UNSCHED 30-90 OB DISPAT( 105522 U 79 NORMAL NO REMARKABLE OBSERVATIONS 190 p - - - 197 p - - - 204 p - - - 211 p 218 p - - - 225 p - - - - - - 232 p - - 239 p 246 p - - - 253 p -- -- -- 226670 pp - - - 274 p - - - 281 p - 288 p - 295 p - 302 p - 309 p - 316 p - 323 p - 330 p 337 p 344 p 351 p 358 p 365 P 441 Appendix 2 Individual Clinical-observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFORIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ------ -------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSE: 0 MG/KG/DAY DAYS 186-365 DAY 'C' - COMMENTS LISTED AT END OF OBSE AM OBS UNSCHED 30-90 OB DISPATI 105529 p 79 EXCRETION LIQUID FECES SKIN & PELAGE ALOPECIA FEET 277 p - - - 278 p - - - 306 p - - - 308 p - - - 186 p - - - 187 p - - - 188 p - - - 189 p - - - 190 p - - - 191 p - - - 192 p - - 193 p - - 194 p - - 195 p - - 197 p 200 p 201 p 203 p 204 p 206 p 210 p 211 p 213 p 216 p 217 p 218 p 219 p 220 p 442 Appendix 2 individual Clinical.Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS -------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSET 0 MG/KG/DAY DAYS 186-365 DAY 'C' - COMMENTS LISTED AT END OF OBS AN OBS UNSCHED 30-90 OB DISPATC (CONTINUED FROM PREVIOUS PAGE) 105529 p 79 SKIN & PELAGE AT,OPECIA FEET 221 p 222 p 223 p 225 p 226 p - - - 229 p - - - 230 p - - - 231 p - - - 232 p - 233 p - 234 p - 235 p - 236 p - 237 p - 238 p - 239 p - 240 p - 241 p - 244 p - 245 p - - - 246 p - - - 247 p - - - 248 p - - - 251 p - - - 252 P - - - 253 p - - - 254 p - - 255 p 257 p 258 p 443 Appendix 2 individual Clinical@observations Recovery idays 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH pERpLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOST-6295) IN CYNOMOLGUS MONKEYS ------- ---------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD ()UALIFIER GROUP: Fl DOSE: 0 MG/KG/DAY DAYS 186-365 DAY 'C' - COMMENTS LISTED AT MO OF OBSERVJ AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105529 p 79 SKIN & PELAGE ALOPECIA FEET 259 p - - - 260 p - - - 261 p 263 p - - - 264 p - - - 265 p - - - - - 266 p - - - 267 p 268 p - - - 269 p - - - 272 p 273 p - - - 274 p - - - - - - 275 p - - - 276 p 277 p - - - 278 p -- -- -- 279 p - - - 280 p 281 p - - - 288 p - - - 289 p - - - 294 p - - - - - 295 p - - - 298 p 301 p - - - 302 p - - - 305 p - - - 306 p - - - 308 p 44 Appendix 2 individual Clinicalobservations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSET 0 MG/KG/DAY DAYS 186-365 DAY *Cl - COMMENTS LISTED AT END OF OBSERVA AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED 105529 P FROM PREVIOUS PAGE) 79 SKIN & PELAGE AtoOPECIA FEET TAIL 309 p - - - 310 p -- -- -- 311 p - - - 314 p 106 p - - - 187 p - - - 188 p - - - 189 p - - - 190 p - 191 p - - - 192 p -- -- -- 193 p 194 p - - - 195 p - - - 197 p - 200 p - 201 p - 203 p - - 204 p - - - 206 p - - - 210 p - - - 211 p - - - 213 p - - - 216 p - - - 217 p - - - 218 p - 219 p - 220 p - 221 p - 222 p - 445 Appendix 2 individual Clinical-observations Recovery (Days 166 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNONOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH NK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSE: 0 NG/KG/DAY DAYS 186-365 DAY -C- - COMMENTS LISTED AT END OF OBSERV@ AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105529 p 79 SKIN & PELAGE ALOPECIA TAIL 223 p - 225 p - - - 226 p - - - 229 p - - - 230 p - - - 231 p - - - 232 p - - - 233 p - - - 234 p - - - 235 p - - - 236 p - - - 237 p - - - 238 p - - - 239 p - - - 240 p - - - 241 p - - - 244 p - - - 245 p - - - 246 p - - - 247 p - - - NORMAL NO REMARKABLE OBSERVATIONS 316 p - - - 323 p - - - 330 p - - - 337 p - - - 344 p - - - 351 p - - - 358 p - - - 365 p - 446 Appendix 2 individual Clinical.Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSE: DAYS 186-365 0 No/KG/DAY DAY -C- - COMMENTS LISTED AT MO OF OBSE AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS 105529 p 79 PAGE) QUALITATIVE LOW FOOD CONSUMPTION 195 p - 210 p - - 247 p - - 248 p - - 260 p - - 272 p - - 273 p - - 294 p - - 105549 P 79 DISCHARGE APPEARS TO BE MENSTRUATING NORMAL NO REMARKABLE OBSERVATIONS 261 p - - 190 p 197 p 204 p 211 p 218 p 225 p 232 p 239 p 246 p 253 p 260 p 267 p 274 p 281 p 288 p 295 p - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 447 Appendix 2 individual clinical-observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWE SULPONIC ACID POTASSIUM SALT (PFOS;T-629S) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSE: 0 MG/KG/DAY DAYS 186-365 DAY 'C' - C014HEMS LISTED AT I= OF OBSERVJ AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105549 p 79 NORMAL NO REMARKABLE OBSERVATIONS 302 p 309 p - - - 316 p - - - 323 p - - - 330 p - - - 337 p - - - 344 p - - - 351 p - - - 358 p - - - 365 p QUALITATIVE LOW FOOD CONSUMPTION 19S p - - - 231 p - - - 246 p - - - 272 p - - - 448 Appendix 2 individual Clinical.Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F3 DOSE: DAYS 186-365 0.15 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSE AN OHS UNSCHED 30-90 08 DISPATCH 105539 6 81 DISCHARGE APPEARS TO BE MENSTRUATING EXCRETION FEW FECES NORMAL NO REMARKABLE OBSERVATIONS 216 p - 217 p - - - 246 p - - - 275 p - - - 191 p - - - 195 p - - - 190 p - - - 197 p - - - 204 p 211 p 218 p 225 p 232 p 239 p 253 p 260 p 267 p 274 p 281 p 288 p 295 p 302 p 309 P 316 p 323 p 330 p 337 p 449 Appendix 2 individual Clinical.observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULFOWIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F3 DAYS DOSE: 186-365 0.15 MG/KG/DAY DAY -Cl - COMMENTS LISTED AT MM OF OBSE AM OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105539 6 81 NORMAL NO REMARKABLE OBSERVATIONS 344 p 351 p 358 p 365 p QUALITATIVE LOW FOOD CONSUMPTION 191 p 195 p - - - 213 p 218 p - - - 251 p - - - 254 p - - - 259 p - - - 269 p - - - 316 p - - - 346 p - - 105552 6 81 NORMAL No REMARKA13LE OBSERVATIONS 190 p - 197 p - 204 p - 211 p - 218 p - 225 p - 232 p - 239 p - 246 p - - 253 p - - 260 p - - 267 p - - 274 p - - 450 Appendix 2 individual clinical-observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE'SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNONOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------- AN114AL DEATH NUMBER CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP- F3 DAYS DOSE: 186-365 0.15 NG/KG/DAY DAY 'C' - CONNENTS LISTED AT END OF OBSERV@ AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105552 6 81 NORMAL NO REMARKABLE OBSERVATIONS 281 p - 288 p - - - 295 p 302 p - - - 309 p - - - - - - 316 p - - - 323 p 330 p - - - 337 p - - 344 p - - - 351 p - - - 350 p 365 p - - - QUALITATIVE LOW FOOD CONSUMPTION 220 p - - - 343 p - - - 344 p 346 p 451 Appendix 2 Individual Clinical.observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------- -------------------------------------------------------------------------------------------------------- ANI14AL DEATH NUMBER CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DAYS DOSE: 186-365 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERV) AM OBS UNSCHED 30-90 OB DISPATCH 105533 u 79 EXCRETION NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 245 p 190 p - - - 197 p 204 p -- -- -- 211 p 218 p - - - 225 p - - 232 p - - - 239 p - - - 246 p - - - 253 p - - - 260 p - - - 267 p - - - 274 p - - 281 p - - - 288 p - - - 295 p -- -- -- 330029 pp - - - 316 p - - - 323 p - - - 330 p - - - 337 p - - - 344 p - - - 3Sl p - - - 358 p - - - 365 p - - - 452 Appendix 2 individual Clinical.observations Recovery (D&yS 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DOSE: DAYS 186-365 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERV AM OHS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS 105533 U 79 PAGE) QUALITATIVE LOW FOOD CONSUMPTION 241 p - - - 244 p - - - 343 p - - - 105542 U 79 DISCHARGE APPEARS TO BE MENSTRUATING 260 p - - - 299 p - - - NORMAL NO REMARKABLE OBSERVATIONS 190 p - - - 197 p - - - 204 p - - - 211 p - - - 218 p - - - 225 p - - - 232 p - - - 239 p - 246 p - - - 253 p - - - 267 p - - - 274 p - - - 288 p - - - 295 p - - - 302 p - - - 309 p - - - 316 p - - - 323 p - - - 330 p - - - 337 p - - - 453 Appendix 2 individual Clinical observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUORDOCTANE SULPONIC ACID POTASSIUM SALT (PFOST-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 186-365 DAY 'C' - COMMENTS LISTED AT END OF OBSE AN OBS UNSCHED 30-90 OB DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105542 u 79 NORMAL NO REMARKABLE OBSERVATIONS 344 p 351 p - - 358 p - - 365 p - - QUALITATIVE LOW FOOD CONSUMPTION 269 p - - 273 p - 275 p - - - 281 p - - - 302 p - - - 343 p - - - 344 p - - - 454 Appendix 2 individual Clinical.observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD ()UALIFIER GROUP: Ml DOSE: 0 MG/KG/DAY DAYS 368-558 DAY c, - COMMENTS LISTED AT END OF OBSERVA AM OBS UNSCH EXTRA DISPATCH 105520 0 79 EXCRETION NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 533 p 534 p 372 p 379 p 386 p 393 p 400 p 407 p 414 p 421 p 428 p 435 p 442 p 449 p 456 p 463 p 470 p 477 p 484 p 491 p 498 p 505 p 512 p 519 p 526 p 540 p 547 p - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 455 Appendix 2 individual Clinical-observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Ml DOSE.- 0 MG/KG/DAY DAYS 368-558 DAY 'C' - COMMENTS LISTED AT END OF OBSEF AN ORS UNSCH EXTRA DISPATCH (CONTINUED FROM PREVIOUS 105520 0 79 PAGE) QUALITATIVE LOW FOOD CONSUMPTION 541 p - - - 105526 0 79 DISCHARGE VOMITUS CONTAINING FOOD 535 p - - - 541 p - - - NORMAL NO REMARKABLE OBSERVATIONS 372 p - - - 379 p - - - 386 p - - - 393 p - - - 400 p - - - 407 p - - - 414 p - - - 421 p - - - 428 p - - - 435 p 442 p 449 p 456 p 463 p 470 p 477 -P 484 p 491 p - 499 p - 505 p - 512 p - 456 Appendix 2 Individual Clinical.Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Ml DOSE: 0 MG/XG/DAY DAYS 368-558 DAY IC, - COMMENTS LISTED AT END OF OBSERVI AM OHS UNSCH EXTRA DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105526 0 79 NORMAL NO REMARKABLE OBSERVATIONS 519 p - 526 p - 533 p - 540 p - 547 p - 457 Appendix 2 individual Clinical-observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOUIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD ()UALIFIER GROUP: M3 DAYS DOSE: 369-550 0.15 MG/KG/DAY DAY -C- - COMMENTS LISTED AT END OF OBSERVI AM OBS UNSCH EXTRA DISPATCH 105505 6 81 APPEARANCE SWOLLEN HEAD-MAXILLARY-RIGHT DISCHARGE VOMITUS CONTAINING FOOD EXCRETION FEW FECES NORMAL NO REMARKABLE OBSERVATIONS 390 p - - - 391 p - - - 393 p - - - 394 p - - - 395 p - - - 397 p - - - 400 p - - 535 p - - 555 p 372 p - - 379 p -- -- -- 386 p - - - 407 p 414 p - - - 421 p 428 p 435 p 442 p 449 p 456 p 463 p 470 p 477 p 458 Appendix 2 individual Clinical-observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 368-558 DAY c, - COMMENTS LISTED AT END OF OBSERV) AM OBS UNSCH EXTRA DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105505 6 81 NORMAL NO REMARKABLE OBSERVATIONS 484 p - - - 491 p - - - 498 p - - - 505 p - - - 512 p - - 519 p - - - 526 p - - - 533 p - - - 540 p - - - 547 p - - - 554 p - - - QUALITATIVE LOW FOOD CONSUMPTION 375 p 376 p 5S5 p 105523 6 81 DISCHARGE VOMITUS CONTAINING FOOD 535 p - - - EXCRETION NO FECES NON-FORMED FECES 555 p - - - 556 p - - - 557 p - - - NORMAL No REMARKABLE OBSERVATIONS 372 p - - - 386 p - - - 393 p - 400 p 459 Appendix 2 individual Clinical observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M3 DOSE: DAYS 368-558 0.15 MG/KG/DAY DAY 'C' - C014MENTS LISTED AT MM AN OBS UNSCH EXTRA OF OBSERVJI DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105523 6 81 NORMAL NO REMARKABLE OBSERVATIONS 407 p - - - 414 p - - - 421 p - - - 428 p - - - 435 p - - - 442 p - - - 449 p - - - 456 p - - - 463 p - - - 470 p - - - 477 p - - - 484 p - - - 491 p - - - 498 p - - - 505 p - - - 512 p - - - 519 p - - - 526 p - - - 533 p - - - 540 p - - 547 p - - 554 p - QUALITATIVE LOW FOOD CONSUMPTION 375 p - 379 p 553 p p 555 p 558 p 460, Appendix 2 individual Clinical-Observatibno Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ------- -----------------------------------7------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 368-558 DAY c, - COMMENTS LISTED AT END OF OBSERV, AM OBS UNSCH EXTRA DISPATCH 105511 U 79 NORMAL NO REMARKABLE OBSERVATIONS 372 p - - 379 p - - - 306 p - - - 393 p - - - 400 p - - - 407 p - - - 414 p - - - - - - 421 p - - - 428 p 435 p - - - 442 p - - - 449 p - - - 456 p - - - 463 p - - - 470 p - - - 477 p - - - 484 p 491 p - - - 498 p - - - 505 p - - - 512 p - - - 519 p - - - 526 p - - - 533 p - - 540 p - - 547 p - - 549 p - - p 461 Appendix 2 Individual Clinicalobservations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- 7 ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUAIJIFIER GROUP: M4 DAYS DOSE: 368-558 0.75 MG/KG/DAY DAY 'C' - COMU24TS LISTED AT END OF OBSERV, AM ORS UNSCH EXTRA DISPATCH 105522 u 79 EXCRETION NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 402 p - 403 p - 372 p - 379 p - 386 p - 393 p - 400 p - - - 407 p - - - 414 P - - - 421 p - - - 428 p - - - 435 p - - - 442 p - - - 449 p - - - 456 p - - - 463 p - - - 470 p - - 477 p - - 484 p - 491 p - - 498 p - - 505 p - - 512 p - - 519 p - - 526 p - - 533 p - - 540 p - - 547 p - - 549 p - p 462 Appendix 2 individual Clinical-Observationo Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE . CATEGORY WK OF KEYWORD DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 368-558 DAY 'C' - COMMENTS LISTED AT END OF OBSERV, AM OBS UNSCH EXTRA DISPATCH (CONTINUED FROM PREVIOUS 105522 U 79 PAGE) ()UALITATIVE FOOD CONSUMPTION LOW 394 p 463 Appendix 2 Individual Clinical-observati6ns Recovery (Days 366 through 561) 26-WEEX CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS -------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSE: 0 NO/XG/DAY DAYS 368-558 DAY -C' - COMMENTS LISTED AT END OF OBSERV, AM OBS UNSCH EXTRA DISPATCH 105529 p 79 EXCRETION LIQUID FECES NON-FORMED FECES SKIN & PELAGE ALOPECIA LIMB-HIND-RIGHT NOR14AL No REMARKABLE OBSERVATIONS 489 p - - - 491 p - - - 492 p - - - 493 P - - - 494 p - - - 496 p - - - 368 p - - - 369 p - - - 372 p - - - 376 p - - - 377 p - - - 378 p - - - 549 p - - - 379 p - - - 386 p - - - 393 p - - - 400 p - - - 407 p 414 P - - - 421 p - - - 428 p - - - 435 p - - - 442 p - - - 449 p - - - 456 p - - - 463 p - - - 464 Appendix 2 individual Clinical 4Dbservations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH CODE WK OF DEATH CATEGORY KEYWORD QUALIFIER GROUP-. Fl DOSE: 0 MG/KG/DAY DAYS 368-558 DAY 'C' - COMMENTS LISTED AT END OF OBSERV AM OBS UNSCH EXTRA DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105529 p 79 NORMAL NO REMARKABLE OBSERVATIONS 470 p - - - 477 p - - - 484 p - - - 498 p - - - 505 p - - - 512 p - - - 519 p - - - 526 p - - - 533 p - - - 540 p - - - 547 p - - - QUALITATIVE LOW FOOD CONSUMPTION 372 p - - - 376 p - - - 452 p - - - iOS549 P 79 DISCHARGE VOMITUS CONTAINING FOOD APPEARS TO BE MENSTRUATING 535 p - - - 372 p - - - 400 p - - - 456 p - - - 484 p - - - 541 p - - - NORMAL NO REMARKABLE OBSERVATIONS 379 p - - - 386 p - - - .393 p - - - 407 p 465 Appendix 2 Individual Clinical-Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNO14OL(;Us MONKEYS -------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fl DOSE: 0 MG/KG/DAY DAYS 368-558 DAY IC- - COMMENTS LISTED AT END OF OBSE AN OBS UNSCH EXTRA DISPATC (CONTINUED FROM PREVIOUS PAGE) 105549 P 79 NORMAL NO REMARKABLE OBSERVATIONS 414 p 421 p - - - 428 p - - - 435 p - - - 442 p - - - 449 p - - - 463 p - - - 470 p - - - 477 p - - - 491 p - - - 498 p - - - 505 p - - - 512 p - - - 519 p - - - 526 p - - - 533 p - - - 540 p - - - 547 p - - - QUALITATIVE LOW FOOD CONSUMPTION 372 p - - - 452 p - - - 466 Appendix 2 Individual Clinical.observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 368-558 DAY 'C' - COMMENTS LISTED AT END OF OBSERV, AN OBS UNSCH EXTRA DISPATCH 105539 6 91 DISCHARGE UNKNOWN SOURCE FOUND IN PAN RED IN COLOR EXCRETION FEW FECES NO FECES NORMAL NO REMARKABLE OBSERVATIONS 555 p - - - 556 p - - - 404 p - - - 558 p - - - 555 p - - - 556 p 557 p - - - 372 p - - - 379 p - - - 386 p - - - 393 p - - - 400 p - 407 p - - 414 p - - 421 p - - 428 p - - 435 p - - 442 p - - 449 p - - 456 p - - 463 p - - 470 p - - 477 p - - 484 p - - 491 p - - 498 p 467 Appendix 2 individual Clinical-observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERPLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNO14OLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F3 DAYS DOSE: 368-558 0.15 MG/KG/DAY DAY IC, - COMMENTS LISTED AT END OF OBSE AM OBS UNSCH EXTRA DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105539 6 81 NORMAL NO REMARKABLE OBSERVATIONS 505 p - - 512 p - - - 519 p - - - 526 p - - - 533 p - - - 540 p - - - 547 p - - - 554 p - - - QUALITATIVE LOW FOOD CONSUMPTION 105552 6 NONE 81 DISCHARGE VOMITUS CONTAINING FOOD EXCRETION FEW FECES NO FECES 375 p - - - 376 p - - - 399 p - - - 404 p - - - 407 p - - - 553 - p - - 556 p - - - 557 p - - - 558 p - - - 555 p - - - 535 p - - - 555 p - - - 557 p 558 p 556 p 468 Appendix 2 individual Clinical.observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------7------------------------------------------- ---------- ------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F3 DAYS DOSE: 368-558 0.15 MG/KG/DAY DAY C. - COMMENTS LISTED AT END OF OBSERVA AM OBS UNSCH EXTRA DISPATCH (CONTINUED FROM PREVIOUS 105552 6 81 PAGE) NORMAL NO REMARKABLE OBSERVATIONS 372 p - - 379 p - - 386 p - - - 393 p - - - 400 p - - - 407 p - - - 414 p - - - 421 p - - - 428 p -- -- -- 435 p - - - 442 p 449 p - - - 456 p - - - 463 p - - - 470 p - - - 477 p - - - 484 p - - - 491 p - - - 498 p - - - 505 p 512 p 519 p 526 p 533 p 540 p 547 p 554 p 469 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERPLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F3 DOSE: DAYS 368-558 0.15 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT END OF OBSERVA AN OBS UNSCH EXTRA DISPATCH (CONTINUED FROM PREVIOUS 105552 6 81 PAGE) QUALITATIVE LOW FOOD CONSUMPTION NONE 372 p - - - 557 p - - - 558 p - - - 555 p - - - 556 p - - - 470 Appendix 2 individual Clinical-observations Recovery idays 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) iw cyNOMOLGUS MONKEYS ----------------------------------------------------- ----------------------------------------------------------- ANIMAL NUMBER DEATH WK OF CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DAYS DOSE: 368-558 0.75 MG/KG/DAY DAY IC, - COMMENTS LISTED,AT END OF OBSERVA AM OBS UNSCH EXTRA DISPATCH 105533 u 79 EXCRETION LIQUID FECES NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 399 p -- -- -- 400 p 402 p - - - 372 p - - - 379 p - - - 386 p - - - 393 p - - - 407 p - 414 p - - - 421 p - - - 428 p - - - 435 p - - - 442 p - - - 449 p - - - 456 p -- -- -- 463 p - - - 470 p 477 p - - - 484 p - - - 491 p - - - 498 p - - - 505 p - - - 512 p - - - 519 p - 526 p - - - 533 p - - - 540 p - - - 547 p - - - 549 p - - p 471 Appendix 2 Individual Clinical-observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLuoROOCTAME SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: Fd DAYS DOSE: 368-558 0.75 MG/KG/DAY DAY 'C' - COMMENTS LISTED AT MM AM OBS UNSCH EXTRA OF OBSERV) DISPATCH (CONTINUED FROM PREVIOUS 105533 u 79 PAGE) QUALITATIVE LOW FOOD CONSUMPTION 394 p - - - 105542 U 79 DISCHARGE APPEARS TO BE MENSTRUATING 496 p - - - DISCHARGE UNKNOWN FOUND IN PAN RED IN COLOR SOURCE 375 p - - - NORMAL NO REMARKABLE OBSERVATIONS 372 p - - - 379 p - - - 386 p 393 p - 400 p - 407 p - - - 414 p - - - 421 p - - - 428 p - - - 435 p - - - 442 p 449 p - - - 456 p -- -- -- 446730 pp - - - 477 p - - - 484 p -- -- -- 491 p - - - 498 p 472 Appendix 2 Individual Clinical observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNONOT-GUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF NUMBER CODE DEATH CATEGORY KEYWORD QUALIFIER GROUP: F4 DOSE: 0.75 NG/KG/DAY DAYS 368-558 DAY -C- - COMMENTS LISTED AT END OF OBSE AM OBS UNSCH EXTRA DISPATCH (CONTINUED FROM PREVIOUS PAGE) 105542 U 79 NORMAL NO REMARKABLE OBSERVATIONS 505 p 512 p - - 519 p - - 526 p - - - 533 p - - - 540 p - - - 547 p - - - 549 p - - p QUALITATIVE t.ow FOOD CONSUMPTION 375 p - - 394 p - - 395 p - - 473 Appendix 2 individual Ophthalmic observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULF-ONIC ACID POTASSIUM SALT (PFOS:T-6295) IN CYNOMOLC;US MONKEYS ----------------------------------------------------------------------------------------------------------------- CATEGORY ANIMAL DEATH WK OF KEYWORD GROUP.- Ml DOSET 0 MG/KG/DAY WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED.BETA 'C' - COMMENTS LISTED AT END OF OBSE N-U-MB-E-R---C-OD-E-----DE-A-TH--------QU-A-L-I-FI-E-R----------------------------------------------------------------------------------- 105508 T 105517 T 105519 T 105520 0 105526 0 105527 T 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4. 26 -4. 26 -4. 26 -4, 26 474 Appendix 2 individual ophthalmic observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLOUS MONKEYS ------- --------------------------------------------------------------------------------------------------------- CATEGORY GROUP: M2 DOSE: 0.03 MG/KG/DAY - ANIMAL DEATH WK OF KEYWORD WEEKS -4 AND 26 OBSERVED DURING THE WEEKS LISTED BETA 'C' - COMMENTS LISTED AT END OF OBSE N-U-M-BE-R---C-OD-E----DE-A-TH--------QU-A-L-I-FI-E-R---------------------------------------------------------------------------------- 105514 T 105515 T 105516 T 105521 T 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4, 26 -4. 26 475 Appendix 2 Individual Ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWS SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------ -------------------------------------------------------------------------------------------------------- CATEGORY GROUP: M3 DOSE: 0.15 MG/KG/DAY WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED BE ANIMAL DEATH WK OF KEYWORD 'C' - COMMENTS LISTED AT END OF OBSE N-U-M-BE-R---C-OD-E----DE-A-TH--------QU-A-L-I-FI-E-R---------------------------------------------------------------------------------- 105505 6 105510 T 105518 T 105523 6 105524 T 105528 T 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4. 26 -4, 26 -4, 26 -4, 26 476 Appendix 2 individual OphthalmiC observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------- CATEGORY GROUP: M4 DOSE: 0.75 MG/KG/DAY WEEKS -4 AND 26 - OBSERVED DURING THE WEE" LISTED BELA ANIMAL DEATH WK OF KEYWORD IC, - COMMENTS LISTED AT END OF OBS N-U-MB-E-R--C-O-DE----DE-A-TH---------Q-U-AL-I-F-IE-R--------------------------------------------------------------------------------- 105506 M 105507 T 105509 D 105511 u 105512 T 105522 U 26 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 23 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 No VISIBLE LESIONS NO VISIBLE LESIONS EYES 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4 -4, 26 -4, 26 -4. 26 477 Appendix 2 individual Ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------- ------------------------------------------------------------------------------------------------------- CATEGORY GROUP: Fl DOSE: 0 MG/KG/DAY WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED BE ANIMAL DEATH WK OF KEYWORD C. - COMMENTS LISTED AT END OF OBSE N-U-M-BE-R---CO-D-E---D-E-A-TH--------QU-A-L-IF-I-E-R --------------------------------------------------------------------------------- 105529 p 105530 T 105531 T 105535 T 105544 T 105549 P 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYE-LEFT EYES MISCELLANEOUS OPHTHALMICS INCREASED MYELINATION OF OPTIC EYE-RIGHT NERVE 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4 26 -4 -4, 26 -4, 26 -4, 26 -4, 26 -4, 26 478 Appendix 2 individual ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ------ -------------------------------------------------------------------------------------------------------- ANIMAL DEATH WK OF CATEGORY KEYWORD GROUP: P2 DOSE: 0.03 MG/KG/Dhy WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED BE 'C' - COMMENTS LISTED AT END OF OBS N-U-M-BE-R---C-OD-E---D-E-A-TH--------QU-A-L-I-FI-E-R--------------------------------------------------------------------------- 105S37 T 105541 T 105547 T 105550 T 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4, 26 -4. 26 479 Appendix 2 individual Ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: F3 DOSE: 0.15 MG/]kG/DAY ANIMAL DEATH WK OF KEYWORD WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED BE NUMBER CODE DEATH QUALIFIER 'C' - COMMENTS LISTED AT EM OF OBSE ---------------------------------------------------------------------------------------------------------------- 105532 T 105538 T 105539 6 105545 T 105548 T 105552 6 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS I EYES 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4, 26 -4, 26 -4,.26 -4, 26 480 Appendix 2 individual ophthalmi6 Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERPLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOT.GUS MONKEYS ---------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: Pt DOSE: 0.75 MG/KG/DAY ANIMAL DEATH WK OF KEYWORD WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED BE NUMBER CODE DEATH QUALIFIER 'C' - COMMENTS LISTED AT END OF OBS ---------------------------------------------------------------------------------------------------------------- 105533 U 105534 T 105536 T 105540 T 105542 u 105551 T 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES - 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4, 26 -4, 26 -4, 26 -4, 26 481 Appendix 2 Individual ophthalmic Observations Recovery- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFMIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: Ml DOSE: 0 MG/KG/DAY ANIMAL DEATH WK OF KEYWORD WEEK 52 - OBSERVED DURING THE WEEKS LISTED BE NUMBER CODE DEATH C)UALIFIER 'C' - COMMENTS LISTED AT END OF OBS -------------------------------------------------------------------------------------------------------------- IOSS20 0 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 105526 0 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 482 Appendix 2 individual Ophthalmic observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: M3 DOSE: 0.15 NO/KG/DAY ANIMAL DEATH WK OF KEYWORD WEEK 52 - OBSERVED DURING THE WEEKS LISTED BELOI 'C' - COMMENTS LISTED AT END OF OBSE N-U-M-BE-R---C-OD-E---D-E-A-TH--------QU-A-L-IF-I-E-R --------------------------------------------------------------------------------- 105505 6 el NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 105523 6 al NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 483 Appendix 2 Individual Ophthalmic Observations Recovery 26-WEEK CAPSULE TOXICXTY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: M4 DOSE: 0.75 MG/KG/DAY ANIMAL DEATH WK OF KEYWORD WEEK 52 - OBSERVED DURING THE WEEKS LISTED BE NUMBER CODE DEATH QUALIFIER 'C' - COMMENTS LISTED AT END OF OBSI ---------------------------------------------------------------------------------------------------------------- 105511 U 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 105522 U 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 .484 Appendix 2 individual ophthalmiq observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: Fl DOSE: 0 MG/KG/DAY ANIMAL DEATH WK OF KEYWORD WEEK 52 - OBSERVED DURING THE WEEKS LISTED BE IC, - COMMENTS LISTED AT END OF OBSE N-U-M-BE-R---C-O-DE----DE-A-T-H-------Q-UA-L-I-FI-E-R------------------------------------------------------------------------------------ 105529 p 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYE-LEFT 52 MISCELLANEOUS OPHTHALMICS OTHER EYE-RIGHT 52C 105549 P 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 485 Appendix 2 Individual Ophthalmic Observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOWIC ACID POTASSIUM SALT (PFOST-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- CATEGORY STUDY KEYWORD ANIMAL GROUP DAY WK QUALIFIER FREE-TEXT COMMENT ------------------------------------------------------------------------------------------------- ------------- 105529 Fl 363 52 MISCELLANEOUS OTHER EYE-RIGHT OPHTHALMICS INCREASED MYELINATION OF OPTIC NERVE HEAD T ASSOCIATED WITH OPTIC NEURITIS. MACULA NORMA 486 Appendix 2 individual Ophthalmiq Observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: F3 DOSE: 0.15 MG/KG/DAY ANIMAL DEATH WK OF KEYWORD WEEK 52 - OBSERVED DURING THE WEEKS LISTED BE NUMBER CODE DEATH QUALIFIER 'C' - COMMENTS LISTED AT END OF OBS --------------------------------------------------------------------------------------------------------------- 105539 6 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 105552 6 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 487 Appendix 2 individual Ophthalmic observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: P4 DOSE: 0.75 MG/KG/DAY ANIMAL DEATH WK OF KEYWORD WEEK 52 - OBSERVED IXMING THE WEEKS LISTED BE NUMBER CODE DEATH ()UALIFIER 'C' - COMMENTS LISTED AT END OF OBSE ---------------------------------------------------------------------------------------------------------------- 105533 U 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 105542 U 79' NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 488 APPENDIX 3 IndividualBody Weight Data (kg) Covance 6329-223 3M T-6295.7 489 Appendix 3 Individual Body Weight Data (kg) Treatment Phase 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOWIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL a b WEEK WEEK WEEK WEEK WEEK WEEK WEEK WEEK WE NUMBER -1 -1 1 2 3 4 5 6 ----------------------------------------------------------------------------------------------------------------- GROUP: MALE 1 - 0 MG/XG/DAY 105508 105517 105519 105520 105526 105527 3.0 3.1 3.1 3.1 3.2 3.2 3.2 3.2 3 3.4 3.4 3.4 3.3 3.2 3.2 3.3 3.3 3 2.9 3.0 3.0 3.0 3.0 3.1 3.1 3.0 3 2.9 2.9 2.9 2.9 3.0 3.1 3.0 3.0 2 3.0 3.0 3.0 3.1 3.2 3.3 3.3 3.3 3 4.0 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4 GROUP: MALE 2 0.03 MG/KG/DAY 105514 105515 105516 105521 3.1 3.1 3.1 3.2 3.2 3.3 3.3 3.3 3 3.3 3.3 3.3 3.2 3.3 3.4 3.4 3.5 3 2.7 2.8 2.8 2.8 2.8 2.9 2.9 2.9 2 4.4 4.3 4.4 4.3 4.4 4.4 4.4 4.4 4 GROUP: MALE 3 0.15 MG/KG/DAY 105505 105510 105518 105523 105524 105528 3.1 3.2 3.2 3.2 3.3 3.3 3.3 3.3 3 2.9 3.0 2.9 2.9 2.9 3.0 .3.0 3.0 3 3.0 3.1 3.1 3.1 3.1 3.2 3.2 3.2 3 2.6 2.7 2.7 2.7 2.8 2.8 2.8 2.8 2 2.9 2.9 2.9 3.0 3.1 3.1 3.1 3.1 3 3.6 3.7 3.7 3.7 3.7 3.8 3.8 3.8 3 GROUP: MALE 4 0.75 MG/KG/DAY 105506 105507 105509 105511 105512 105522 3.3 3.4 3.4 3.4 3.5 3.5 3.6 3.7 3 4.4 4.4 4.4 4.5 4.5 4.5 4.5 4.5 4 3.1 3.2 3.2 3.1 3.2 3.2 3.3 3.3 3 2.8 2.9 2.9 2.9 2.9 2.9 2.8 2.8 2 2.8 2.9 2.9 2.8 2.9 3.0 3.0 3.0 3 3.4 3.4 3.4 3.4 3.5 3.6 3.6 3.6 3 a Day -7. b Day -1. 490 Appendix 3 individual Body Weight Data (kg) Treatment Phase 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL WEEK a WEEK b WEEK WEEK WEEK WEEK WEEK WEEK WE] NUMBER -1 -1 1 2 3 4 5 6 ----------------------------------------------------------------------------------------------------------------- GROUP: FEMALE 1 - 0 MG/KG/DAY 105529 105530 105531 105535 105544 105549 2.5 2.5 2.5 2.7 2.3 2.4 2.4 2.4 2 2.9 2.9 2.9 2.8 2.9 2.9 2.7 2.7 2 2.6 2.6 2.6 2.6 2.6 2.7 2.6 2.6 2 3.4 3.3 3.3 3.3 3.4 3.4 3.4 3.4 3 2.6 2.7 2.7 2.6 2.6 2.7 2.7 2.6 2 2.9 2.9 2.9 2.9 3.0 3.0 3.0 3.0 3 GROUP: FEMALE 2 - 0.03 MG/KG/DAY 105537 105541 105547 105550 3.8 3.8 3.9 3.9 3.9 4.0 3.9 3.9 4 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.6 2 2.9 2.9 2.9 3.0 3.0 3.0 3.o 3.0 3 2.9 2.9 2.9 2.9 2.9 2.8 2.8 2.8 2 GROUP: FEMALE 3 0.15 MG/KG/DAY 105532 105538 105539 105545 105548 105552 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2 3.2 3.2 3.2 3.1 3.1 3.0 3.o 3.0 3 3.6 3.7 3.7 3.8 3.8 3.8 3.8 3.9 3 2.6 2.6 2.6 2.7 2.7 2.7 2.6 2.6 2 2.8 2.9 2.9 3.0 2.9 3.0 3.0 3.0 3 2.8 2.8 2.8 2.7 2.7 2.7 2.7 2.7 2 GROUP: FEMALE 4 0.75 MG/KG/DAY 105533 105534 105536 105540 105542 105551 2.6 2.6 2.6 2.6 2.6 2.6 2.5 2.6 2 2.8 2.8 2.8 2.8 2.8 2.8 2.8 2.8 2 3.9 3.9 3.9 3.8 3.8 3.9 3.9 3.9 3 2.9 3.0 3.0 3.1 3.1 2.8 2.6 2.6 2 2.8 2.9 2.8 2.8 2.8 2.8 2.8 2.0 2 2.3 2.4 2.4 2.4 2.4 2.4 2.4 2.3 2 a Day -7. b Day -1. 491 Appendix 3 individual Body Weight Data (kg) Treatment Phase 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL WEEK WEEK WEEK WEEK WEEK WEEK WEEK 'WEEK NUMBER 9 10 11 12 13 14 15 16 ---------------------------------------------------------------------------------------------------------------- GROUP: MALE I - 0 MG/KG/DAY 105508 105517 105519 105520 105526 105527 3.2 3.2 3.2 3.3 3.3 3.3 3.3 3.3 3.4 3.3 3.3 3.3 3.3 3.3 3.3 3.1 3.1 3.1 3.1 3.1 3.2 3.2 3.2 3.2 3.0 3.0 3.1 3.0 3.0 3.1 3.0 3.0 3.4 3.4 3.5 3.5 3.6 3.5 3.6 3.6 4.2 4.2 4.3 4.3 4.3 4.3 4.3. 4.3 GROUP: MALE 2 0.03 MG/KG/DAY 105514 105515 105516 105521 3.3 3.3 3.4 3.4 3.4 3.4 3.5 3.5 3.5 3.5 3.6 3.7 3.7 3.6 3.6 3.7 3.0 3.0 3.0 3.0 3.1 3.2 3.2 3.2 4.4 4.4 4.6 4.6 4.6 4.5 4.6 4.6 GROUP: MALE-3 0.15 MG/KG/DAY 105505 105510 105518 105523 105524 .105528 3.3 3.2 3.3 3.3 3.3 3.2 3.3 3.3 3.1 3.1 3.2 3.2 3.3 3.1 3.2 3.2 3.3 3.2 3.2 3.3 3.3 3..2 3.2 3.3 2.9 2.7 2.9 2.8 2.9 2.9 2.9 2.9 3.2 3.0 3.1 3.1 3.1 3.1 3.1 3.1 3.7 3.7 3.7 3.7 3.8 3.8 3.7 GROUP: KALE 4 0.75 MG/KG/DAY 105506 105507 105509 iossii 105512 105522 3.8 3.7 3.9 3.8 3.9 3.8 3.9 3.9 4.7 4.6 4.7 4.7 4.7 4.6 4.6 4.5 3.2 3.2 3.2 3.2 3.2 3.1 3.1 3.0 2.9 2.8 2.9 2.9 2.9 2.9 2.9 2.8 3.1 3.0 3.1 3.1 3.1 2.9 2.9 2.7 3.6 3.6 3.7 3.6 3.7 3.7 3.7 3.6 492 Appendix 3 individual Body Weight Data (kg) Treatment Phase 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL WEEK WEEK WEEK WEEK WEEK WEEK WEEK WEEK w NUMBER 9 10 11 12 13 id is 16 ---------------------------------------------------------------------------------------------------------------- GROUP: FEMALE 1 - 0 MG/KG/DAY 105529 105530 105531 105535 105544 105549 2.5 2.5 2.5 2.6 2.6 2.6 2.4 2.5 2.9 2.9 3.0 3.1 3.0 3.0 3.0 3.0 2.7 2.6 2.7 2.7 2.7 2.7 2.7 2.7 3.6 3.5 3.5 3.6 3.6 3.6 3.5 3.5 2.6 2.7 2.7 2.7 2.8 2.7 2.7 2.8 3.0 3.0 2.9 3.0 3.0 3.0 3.0 3.0 GROUP: FEMALE 2 0.03 MG/KG/DAY 105537 105541 105547 105550 4.1 4.0 4.0 4.0 4.1 4.1 4.1 4.1 2.6 2.6 2.7 2.7 2.7 2.7 2.7 2.7 3.0 3.0 3.0 3.1 3.1 3.1 3.0 2.9 2.8 2.8 2.8 2.9 2.9 2.9 2.9 GROUPT FEMALE 3 0.15 MG/KG/DAY 105532 105538 105539 105545 105548 105552 2.8 2.8 2.8 2.8 2.8 2.8 2.8 2.8 3.0 3.0 3.2 3.2 3.3 3.2 3.3 3.3 3.9 3.9 3.9 3.9 3.9 4.0 4.0 3.9 2.6 2.7 2.7 2.6 2.6 2.7 2.7 2.7 3.0 3.0 3.0 3.1 3.1 3.1 3.1 3.0 2.8 2.8 2.7 2.7 2.0 2.8 2.8 2.8 GROUP: FEMALE 4 0.75 MG/KG/DAY 105533 105534 105536 105540 105542 105551 2.6 2.6 2.6 2.7 2.7 2.6 2.6 2.6 2.9 2.8 2.8 2.8 2.8 2.8 2.8 2.8 3.9 3.9 3.8 3.8 3.7 3.6 3.5 3.4 3.1 3.0 2.8 2.8 2.8 2.7 2.9 3.0 2.8 2.7 2.7 2.7 2.7 2.7 2.6 2.6 2.3 2.3 2.3 2.3 2.3 2.3 2.4 2.3 493 Appendix 3 Individual Body Weight Data (kg), Treatment Phase 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL WEEK WEEK WEEK WEEK WEEK WEEK WEEK WEEK m NUMBER 19 20 21 22 23 24 25 26 2 -------------------------------------------------------------------------------------------------------------- GROUP: MALE 1 - 0 MG/KG/DAY 105508 105517 105519 105520 105526 105527 3.4 3.4 3.4 3.4 3.4 3.4 3.6 3.6 3.4 3.4 3.3 3.3 3.3 3.4 3.4 3.3 3.3 3.2 3.2 3.2 3.3 3.3 3.4 3.4 3.1 3.0 3.1 3.1 3.1 3.0 3.2 3.2 3.7 3.7 3.7 3.8 3.7 3.7 3.8 3.9 4.5 4.5 4.6 4.6 4.7 4.8 4.9 5.0 GROUP: KALE 2 0.03 MG/KG/DAY 105514 105515 105516 105521 3.6 3.6 3.6 3.6 3.7 3.7 3.8 3.8 3.8 3.8 3.6 3.7 3.7 3.7 3.9 3.8 3.2 3.2 3.2 3.3 3.3 3.3 3.4 3.4 4.6 4.6 4.7 4.6 4.6 4.7 4.7 4.7 GROUP: MALE 3 O.lS MG/KG/DAY 105505 105510 105518 105523 105524 105528 3.3 3.3 3.2 3.3 3.3 3.3 3.4 3.3 3.3 3.3 3.2 3.3 3.3 3.4 3.5 3.4 3.3 3.3 3.2 3.3 3.3 3.3 3.3 3.4 3.0 3.0 2.9 2.9 2.9 2.9 3.1 3.0 3.3 3.3 3.2 3.3 3.3 3.3 3.4 3.4 3.6 3.7 3.7 3.7 3.7 3.7 3.7 3.6 GROUP: MALE A 0.75 MG/KG/DAY 105506 105507 105509 105511 105512 105522 4.0 4.0 3.9 3.9 3.9 4.0 4.0 3.9 4.5 4.4 4.3 4.2 4.2 4.1 4.2 4.2 3.0 3.1 2.9 3.0 2.8 2.9 2.9 2.6 2.7 2.7 2.8 2.7 2.6 2.6 2.5 2.6 2.8 2.7 2.6 2.7 2.7 3.7 3.6 3.6 3.6 3.6 3.6 3.7 3.7 494 Appendix 3 Individual Body Weight Data (kg) Treatment Phase 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------ ANIMAL WEEK WEEK WEEK WEEK WEEK WEEK WEEK 25 WEEK 26 WE 2 NUMBER 19 20 21 22 23 24 ---------- -------------------------------------------------------------- -------------------------------------- GROUP: FEMALE I - 0 MG/KG/DAY 105529 105530 105531 105535 105544 105549 2.5 2.5 2.5 2.5 2.5 2.6 2.5 2.5 3.1 3.0 2 3 3.0 3.0 2.9 3.0 3.0 2.8 2.7 3.0 2.7 2.8 2.8 2 23..85 23..58 23..75 32..68 32..48 32..58 32..69 32..69 32 3.0 3.1 3 2.8 3.1 2.8 3.1 2.8 3.0 3.1 3.0 3.0 GROUP: FEMALE 2 - 0.03 MG/KG/DAY 105537 105541 105547 105550 4.2 4.2 4.2 4.2 4.2 4.3 2.7 4.4 2.8 4.4 2.8 2.7 2.7 2.6 2.7 2.8 2.7 2.8 2.7 33..10 33..00 32..09 23..90 22..89 3.0 3.1 3.0 GROUP: FEMALE 3 - 0.15 MG/KG/DAY 105532 105538 105539 105545 105548 I05S52 2.8 2.8 2.7 2.8 2.8 2.8 2.8 2.8 3.4 3.4 3.3 3.5 3.5 3.8 3.4 3.9 3.5 3.9 3.4 3.9 4.0 4.0 3.8 2.6 3.8 2.7 2.6 2.7 2.7 2.7 2.7 2.8 3.1 3.1 3.0 3.1 3.1 3.1 3.1 3.1 2.8 2.8 2.7 2.8 2.9 2.8 2.9 2.8 GROUPT FEMALE 4 0.75 MG/KG/DAY 105533 105534 105536 105540 105542 105551 2.6 2.6 2.6 2.6 2.6 2.7 2.9 2.7 2.8 2.7 2.7 2.9 2.8 2.7 2.9 2.8 3.3 3.3 3.4 3.3 3.3 3.4 33..51 33..50 32..06 22..79 22..96 32..06 32..70 32..06 2.7 2.4 2.7 2.4 2.4 2.4 2.4 2.4 2.4 2.4 495 Appendix 3 Individual Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER WE2E8K WE2E9K WE3E0K WE3E1K WE3E2K WE3E3K WE3E4K WE3E5K ----------------------------------------------------------------------- -------------------------------------- GROUP: 105520 105526 GROUP: 105505 105523 GROUP: 105511 105522 GROUP: 105529 105549 GROUP: 105539 IOSS52 GROUP: 105533 105542 MALE 1 - 0 MG/XG/DAY 3.2 3.3 3.8 3.9 MALE 3 - 0.15 MG/KG/DAY 3.2 3.3 2.9 2.9 MALE 4 - 0.75 MG/KG/DAY 2.7 2.8 3.5 3.7 PEHALE 1 - 0 MG/KG/DAY 2.4 2.4 2.9 3.0 FEMALE 3 - 0.15 MG/KG/DAY 3.8 3.9 2.8 2.9 FEMALE 4 - 0.75.MG/KG/DAY 2.5 2.6 2.7 2.8 3.3 3.9 3.2 2.8 2.9 3.7 2.4 2.9 3.8 2.8 2.6 2.9 3.4 4.0 3.3 2.8 3.0 4.0 2.4 3.0 3.9 2.8 2.6 2.9 3.5 4.1 3.4 2.9. 3.0 4.2 2.5 3.0 4.0 2.9 2.7 3.2 3.5 4.1 3.4 3.0 3.1 4.2 2.5 3.1 4.0 2.9 2.8 3.2 3.5 4.1 3.3 3.0 3.1 4.5 2.5 3.0 4.0 2.8 2.8 3.2 3.5 4.0 3.3 2.9 3.0 4.4 2.5 3.0 4.1 2.8 2.8 3.1 496 Appendix 3 Individual Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYWOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL WEEK WEEK WEEK WEEK WEEK WEEK WEEK WEEK NUMBER 38 39 40 41 42 43 44 45 ---------------------------------------------------------------------------------------------------------------- GROUP: 14ALE 1 - 0 MG/KG/DAY 105520 105526 3.6 3.6 3.6 3.7 3.8 3.8 4.0 4.1 4.2 4.1 4.1 4.3 4.2 4.2 4.4 4.4 GROUP: MALE 3 - 0.15 MG/KG/DAY 105505 105523 3.3 3.3 3.3 3.4 3.3 3.3 3.4 3.5 3.0 2.9 2.9 3.1 3.0 3.0 3.1 3.1 GROUP: MALE 4 - 0.75 MG/KG/DAY 105511 105522 3.1 3.0 2.9 3.1 3.0 3.1 3.2 3.2 4.5 4.4 4.4 4.5 4.5 4.5 4.5 4.5 GROUP: FE14ALE 1 - 0 MG/KG/DAY I05S29 105549 2.5 2.4 2.3 2.5 2.4 2.4 2.5 2.5 3.0 3.0 2.9 3.1 3.0 3.0 3.0 3.1 GROUP: FEMALE 3 - 0.15 MG/KG/DAY 105539 105552 4.1 4.1 4.0 4.2 4.1 4.1 4.3 4.2 2.9 2.9 2.8 3.0 3.0 3.0 3.0 3.1 GROUP: FEMALE 4 - 0.75 MG/KG/DAY 105533 105542 2.7 2.7 2.8 2.8 2.7 2.7 2.8 2.8 3.3 3.2 3.1 3.3 3.2 3.3 3.3 3.3 497 Appendix 3 Individual Body Wei@ht Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------- ANIMAL WEEK WEEK WEEK WEEK WEEK WEEK WEEK WEEK WE NUMBER 48 49 50 51 52 53 54' 55 5 ----------------------------------------------------------------------------------------------------------------- GROUP: 105520 M&LE 1 - 0 NO/KG/DAY 4.1 4.1 4.1 4.1 4.2 4.2 4.2 4.3 4 105526 4.3 4.4 4.4 4.4 4.5 4.5 4.6 4.7 4 GROUP: MALE 3 - 0.15 MG/KG/DAY: 105505 105523 3.4 3.4 3.4 3.4 3.4 3.4 3.4 3.4 3 3.0 3.1 3.0 3.1 3.1 3.0 3.1 3.1 3 GROUP: MALE 4 - 0.75 MG/KG/DAY: 105511 105522 3.3 3.5 3.5 3.6 3.7 3.7 3.8 3.8 3 4.4 4.6 4.5 4.5 4.5 4.4 4.5 4.4 4 GROUP: FEMALE 1 - 0 MG/KG/DAY% 105529 105549 22..38 23..05 22..49 23..40 22..59 22..48 22..48 22..49 22 GROUP: FEMALE 3 - 0.15 MG/KG/DAYt 105539 105552 4.3 4.3 4.2 4.3 4.3 4.3 4.2 4.2 4 2.9 3.0 2.9 3.0 3.0 2.9 2.9 2.8 2 GROUP: FEMALE 4 - 0.75 MG/KG/DAY: 105533 105542 2.7 2.9 2.8 2.8 2.8 2.7 2.7 2.6 2 3.4 3.4 3.3 3.3 3.4 3.4 3.4 3.5 3 498 Appendix 3 Individual Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPOWIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL WEEK WEEK WEEK WEEK WEEK WEEK WEEK WEEK m NUMBER 5B 59 60 61 62 63 64 65 ---------------------------------------------------------------------------------------------------------------- GROUP: MALE 1 - 0 MG/KG/DAY 105520 105526 4.2 4.1 4.2 4.2 4.1 4.1 4.0 4.0 4.7 4.7 4.9 4.9 4.8 4.9 4.9 4.8 GROUP: HALE 3 - 0.15 MG/KGIDAY: 105505 105523 3.4 3.4 3.5 3.5 3.6 3.5 3.5 3.4 3.2 3.2 3.3 3.3 3.3 3.3 3.3 3.3 GROUP: KALE 4 - 0.75 MG/KG/DAY: 105511 105522 3.9 3.8 4.0 4.0 4.0 4.1 4.3 4.2 4.4 4.4 4.6 4.6 4.7 4.7 4.6. 4.5 GROUP: FEMALE 1 - 0 MG/KG/DAY: 105529 105549 2.5 2.4 2.5 2.5 2.4 2.5 2.4 2.4 2.9 2.9 3.0 2.9 3.0 3.0 2.9 2.9 GROUP: FEMALE 3 - 0.15 MG/KG/DAY: 105539 105552 4.1 4.0 4.2 4.1 4.1 4.1 4.1 4.0 3.0 3.0 3.0 3.0 3.0 3.1 3.0 2.9 GROUP: FEMALE 4 - 0.75 MG/KG/DAY: 105533 105542 2.6 2.6 2.8 2.8 2.8 2.8 2.7 2.7 3.4 3.4 3.5 3.5 3.6 3.6 3.6 3.5 499 Appendix 3 individual Body Weig)ltData (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PLPRFLUOR60CTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL WEEK WEEK WEEK WEEK WEEK WEEK WEEK WEEK NUMBER 68 69 70 71 72 73 74 75 ---------------------------------------------------------------------------------------------------------------- GROUP: MALE 1 - 0 MG/KG/DAY 105520 4.2 4.3 4.2 4.2 4.3 4.2 4.2 4.2 105526 5.0 5.1 5.0 5.1 5.3 5.2 5.4 5.3 GROUP: MALE 3 - 0.15 HG/KG/DAY: 105505 105523 3.6 3.6 3.5 3.5 3.6 3.5 3.6 3.6 3.3 3.4 3.4 3.4 3.5 3.4 3.5 3.5 GROUPT MALE 4 - 0.75 MG/KG/DAY: 105511 105522 4.3 4.3 4.3 4.2 4.3 4.2 4.3 4.3 4.6 4.7 4.6 4.6 4.6 4.5 4.6 4.6 GROUP: FEMALE 1 - 0 MG/KG/DAY: 105529 105549 2.4 2.5 2.4 2.4 2.4 2.4 2.4 2.5 2.9 2.9 2.9 2.9 2.9 2.9 3.0 2.9 GROUP: FEMALE 3 - 0.15 MG/KG/DAY: 105539 105552 4.1 4.2 4.1 4.2 4.2 4.2 4.2 4.2 3.0 3.0 3.0 3.0 3.1 3.0 3.1 3.1 GROUP: FEMALE 4 - 0.75 MG/KG/DAY: 105533 105542 2.7 2.7 2.7 2.7 2.7 2.6 2.7 2.7 3.6 3.7 3.7 3.7 3.8 3.7 3.8 3.8 500 Appendix 3 Individual Body Weiiht Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL WEEK WEEK WEEK NUMBER 78 79 80 ----------------------------------------------------------------------------------------------------------------- GROUP: 105520 105526 MALE 1 - 0 MO/KG/DAY 4.0 4.0 5.3 5.3 GROUP: MALE 3 - 0.15 MG/KG/DAY 105505 105523 3.5 3.5 3.5 3.4 3.5 3.2 GROUP: MALE 4 - 0.75 MG/KG/DAY 105511 105522 4.3 4.4 4.5 4.5 GROUP: FEMALE I - 0 MG/KG/DAY 105529 105549 @.4 2.4 2.0 2.9 GROUP: FEMALE 3 - 0.15 MG/KG/DAY 105539 105552 4.1 4.2 4.0 2.9 3.0 2.8 GROUP: FEMALE 4 - 0.75 MO/KG/DAY 105533 105542 2.@ 2.7 3.8 3.9 501 THE AMERICAS +1.888.COVANCE 2682623i EUROPE +44 tO)1423.500888 ASIA +65.5677333 AUSTRALIA +61.2.B879.2000 E-mail info@ covance.com Visitthe Covance Web Site www.covance.com COVANCE LABORATORIES Madison. Wl. USA 888-541 -LABS (5227) Vienna,VA, USA 888-541 -LABS (5227) Harrogate.UK Oll 44 1423 5000011 M6nster. Germany Oll 49 251 785091 C 0 V A--ilC@E@@ THE DEVELOPMENT SERVICES COMPANY Shaping Solutions C,,,,arcaen:scevencen;tL.;ci,@ce.jc,@ay.m--any,n.a*,.@rc.u,ares!n P-@ce,@n USA. C@@ancL-,stt-@@e.arketmg a,-. a.-o.not@e --eusisof-Coyarco' ,f,ers4o @5nec,@ s@cvdwes. p-,c!;cat:on DraftReport 26-Week CapsuleToxicityStudywithPerfluorooctanSeulfOnic Acid PotassiumSalt(PFOS; T-6295)inCynomolgus Monkeys PREPARED FOR: 3M COVANCE STUDY NUMBEEL-. 6329-223 VOLLTME iiOf n C 0 V A14-C'E-.@-\ Tnow4gw#ARNTSSMCU COMPAW Sponsor. 3M SL PauL Minnesota UNALTD= DRAFR April12,2000 FINAL REPORT Study Tide: 26-Week Capsule ToxicityStudy with PerfluorooctaneSulfonicAcid Potassium Salt(PFOS; T-6295) inCynomolgus Monkeys Author: PeterJ.Thomford, PhD Study Completion Date: To be determined Testing Facility: Covance LaboratoriesInc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595 Laboratory Study Identification: Covance 6329-223 SponsorStudyIdendflcation: 3M StudyNo. T-6295.7 Volume B of H Page 502 of 821 Covance 6329-223 3M T-6295.7 CONTENTS VOLUME H OF H Page APPENDIX 4...................................................*.*..*.*.,.*...5.0.4.............. individuaCllinicaHlematology Data......................................5.0.5............... individualClinicaClhemistryData......................................;.....5.6.5.............. individuaCllinicaUlrinalysiDsata........................................6.3.7.............. APPENDIX 5...........................................................6.8.5.............. IndividuaPlalmitoylCoA OxidaseDetermination.s..........................6.8.6.............. individuaAlnatomic PathologyData ......................................6.9.0............... APPENDIX 6...........................................................7.6.9.............. Summary and IndividuaBllood Hormone Determinatio.n......................7.7.0.............. APPENDIX 7...........................................................8.0.8.............. CeR ProliferatiRoenport ................................................8.0.9.............. 503 APPENDIX4 IndividuaCllinicalHematology Data IndividuaCllinicalCbernistryData IndividuaCllinicalUrinalysiDsata Comce 6329-223 3M T-6295.7 504 ANIMAL NUMBER ------ Group: 1 105508 105517 105519 105520 105526 iOS527 MEAN S.D. N Group% 2 105514 105515 105516 105521 KEAN S.D. N Group.- 3 105505 105510 105518 105523 105524 105528 ME" S.D. N Appendix 4 Individual Clinical Hematology Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Rpc HGB HCT mcv MCH MCHC PIF RETIC X10 /,uL G/DL t FL PG % X10 /,uL t x -------- -------- -------- -------- -------- -------- -------- -------- --- Dose Level: 0 Dosage Unit: mg/kg/day 6.48 12.3 40.3 62.2 19.0 30.5 419 .3 6.25 12.8 42.4 67.8 20.5 30.2 380 .5 6.97 12.5 42.9 61.5 17.9 29.0 577 .5 6.27 11.8 39.4 62.9 18.8 29.9 681. .0 6.48 12.0 41.1 63.5 18.6 29.3 472 .2 6.27 12.1 40.9 65.3 19.3 29.6 652 .3 6.45 12.2 41.2 63.9 19.0 29.8 530 .3 .275 .36 1.30 2.32 .87 .56 125.0 .19 6 6 6 6 6 6 6 6 Dose Level: 0.03 Dosage Unit: mg/kg/day 7.28 6.22 6.67 7.79 12.5 11.8 12.5 12.9 6.99 .688 4 12.4 .46 4 Dose Level: 0.15 6.45 6.58 7.36 6.73 6.76 6.67 12.6 11.9 13.0 12.8 13.0 12.6 6.76 .315 6 12.6 .41 6 45.5 39.8 40.9 45.3 62.5 64.0 61.3 58.1 17.2 10.9 18.7 16.6 42.9 2.95 4 61.5 2.51 4 17.8 1.13 4 Dosage Unit% mg/kg/day 42.0 39.7 44.8 43.1 44.6 43.1 65.2 60.3 60.9 @4.1 66.1 64.6 19.6 18.1 17.6 19.0 19.-3 18.9 42. 8 6 63.5 2.38 6 18.7 .76 6 27.5 29.6 30.6 20.5 29.0 1.34 4 30.0 29.9 29.0 29.7 29.2 29.3 29.5 .41 6 469 675 341 013 574 210.3 4 469 546 375 569 635 366 493 109.0 6 .5 .6 .1 .2 .4 .24 4 1.4 .5 .7 .0 .0 .3 .5 .53 6 ANIMAL NUMBER Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULPONIC ACID MONKEYS RPC HGB HCT mcv MCH MCHC Py RETIC x X10 /,uL G/DL -------- FL -------- -------- PG -------- -------- XIO /AL -------- -------- DoSe Level: 0.75 7.63 6.94 6.89 5.90 7.20 6.73 13.4 12.0 11.9 11.4 13.1 13.1 6.88 .575 6 12.5 .82 6 Dosage Unit: mg/kg/day 45.8 41.5 42.3 40.3 44.5 44.1 60.0 59.7 61.4 68.4 61.8 65.5 17.6 17.3 17.3 19.4 18.1 19.5 43.1 2.06 6 62.8 3.44 6 18.2 1.01 6 29 3 28:9 28.1 28.4 29.3 29.7 29.0 .61 6 519 58 409 528 342 636 415 202.6 6 .6 .3 .4 1.4 .2 .1 .5 .47 6 506 ANIMAL NUMBER ------ Group: 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105S21 MEAN S.D. N Groupt 3 105505 105510 105518 105523 105524 105528 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNO14OLGUS MONKEYS "C N-.%EG LNPH -MONP EO.@IN BAS9 N-SEG% LYMPH% MONO% EO XIO /jAL XIO'IML Xl 0 luL X10 /,uL X10 /.uL X10 /PL -------- -------- -------- -------- -------- -------- -------- -------- -------- --- Dooe Level: 0 6.6 2.1 9.2 3.3 6.7 3.1 9.0 5.1 11.3 5.4 8.9 4.4 8.6 1.76 6 3.9 1.28 6 Dose Level: 0.03 11.7 7.2 11.5 3.2 9.5 4.0 11.1 6.3 11.0 1.00 4 5.2 1.80 4 Dose Level: 0.15 12.5 11.1 10.7 15.0 9.4 12.7 11.9 1.95 6 9.4 5.8 4.8 9.8 4.2 5.3 6.6 2.42 6 Dosage Unit; mg/kg/day 4.0 .4 .0 4.7 1.0 .1 3.1 .4 .2 3.0 .8 .0 5.3 .5 .1 3.7 .7 .1 4.0 .6 .1 .90 .24 .08 6 6 6 Dosage Unit: mg/kg/day 4.0 .4 .2 6.2 1.5 .5 4.4 .9 .1 4.0 .6 .2 4.6 1.05 4 .8 .2 .48 .17 4 4 Dosage Unit: mg/kg/day 2.4 .6 .1 4.2 1.0 .1 4.6 1.3 .0 3.7 .8 .6 4.0 1.1 .0 5.9 .8 .7 4.1 1.14 6 .9 .2 .25 .31 6 6 .0 .1 .0 .1 .0 .0 .0 .05 6 .0 .0 .0 .0 .0 .00 4 .0 .0 .0 .0 .1 .0 .0 .04 6 32 36 46 56 48 49 44 8.9 6 62 28 42 56 47 15.2 4 75 52 45 66 as 42 54 13.4 6 61 52 46 34 47 41 47 9.2 6 34 54 47 36 43 9.4 4 19 38 43 25 42 46 36 10.9 6 6 11 5 9 5 8 7 2.4 6 3 13 10 6 8 4.4 4 5 9 12 5 12 6 a 3.3 6 507 ANIMAL NUMBER ------ Group: 4 105506 105507 IOSS09 105511 105512 105522 MEAN S.D. Appendix 4 individual Clinical Hematology Date males Day -27 26-WEEK CHPSULE TOXICITY STUDY WITH PERFLUOROOCTANR POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID W PC N-YG LIPH MTP EOIIM BAS9 N-SEG% LYMPH% MONO% RO., XIO /,UL XID /jwL XIO liAL XIO liAL XIO /,UL X10 liAL -------- -------- -------- -------- -------- -------- -------- -------- -------- Dose Level: 0.75 Dosage Unit: mg/kg/day 9.3 3.0 5.0 1.1 .2 .1 13.1 4.9 6.3 2.1 .1 .2 7.5 3.3 2.8 .7 .7 .0 8.0 3,9 3.3 .6 .1 .0 7.1 1,6 4.3 1.2 .0 .0 11.0 5.5 4.1 1.1 .2 .1 9.4 3.7 4.3 1.1 .2 .1 2.53 1.40 1.25 .53 .25 6 6 6 6 6 6 32 36 44 49 22 50 39 10.9 6 54 46 37 41 60 37 46 9.5 6 12 is 9 9 16 10 12 3.3 6 Appendix 4 individual Clinical Hematology Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NMBER ------ ANISO POLY POIK HYPO TOXNEUT -------- -------- -------- -------- -------- Group: 1 105508 105517 105519 105520 105526 105527 Dose Level: 0 - - - - - - - - Dosage Unit: mg/kg/day Group: 2 105514 105515 105516 105521 Dose - Level: - 0.03 Dosage Unit: mg/kg/day - - - - - - - - - - - - Group: 3 105505 lossio 105518 105523 105524 105528 Dose Level: 0.15 - Dosage Unit: mg/kg/day Group. 4 ros5o6 105507 105509 105511 105512 105522 Dose Level: 0.75 - - - - - - - - - - - - Dosage unitt mg/kg/day - - - - - - - - - - - - - - - - ANIMAL N-U-MB-E-R-- Group: I 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID Rpc HGB HCT Xio /,uL G/DL t -------- -------- -------- mcv FL ------- MCH PG --- ---- MCHC P!F RETIC t X10 /.uL t x -------- -------- -------- --- Dose Level: 0 5.96 6.78 5.72 6.66 4.98 6.45 11.5 13.3 10.5 12.2 11.6 12.6 6.09 .681 6 12.0 .97 6 Dose Level: 0.03 6.13 5.78 6.30 7.02 10.6 12.0 10 7 12:8 6.31 .522 4 11.5 1.06 4 Dosage Unit: mg/kg/day 37.1 45.0 34.7 40.8 36.2 41.9 39.3 3.93 6 62.2 66.4 60.6 61.3 72.7 65.0 64.7 4.51 6 19.3 19.6 18.3 18.3 23.2 19.5 19.7 1.81 6 Dosage unit: mg/kg/day .36.7 40.0 37.4 43.9 59.9 69.1 59.3 62.5 17.3 20.8 17.0 18.2 39.5 3.26 4 62.7 4.49 4 18.3 1.73 4 31.0 29.S 30.2 29 9 31:9 30.1 30.4 .87 6 28.8 30.2 28.6 29.1 29.2 71 4 631 S52 584 577 471 417 539 79.5 6 .4 .3 .1 .5 1.3 1.0 .6 .46 6 529 .3 426 .9 558 .4 414 .2 482 .4 72.4 .31 4 4 Dose Level: 0.15 Dosage Unit: mg/kg/day 6.95 12.7 43.2 62.2 18.2 29.3 433 .4 6.16 11.3 38.3 62.1 18.4 29.6 475 .3 6.23 11.7 39.2 62.9 18.8 29.9 477 .8 6.72 12.3 40.7 60.6 18.3 30.1 325 .1 6.76 ll.a 38.0 56.2 17.4 31.0 615 .4 6.39 12.0 41.1 64.2 18.7 29.1 560 .7 6.54 12.0 40.1 61.4 18.3 29.0 481 .4 .320 .49 1.97 2.79 .50 .68 100.9 .26 6 6 6 6 6 6 6 6 510 ANIMAL NUMBER ------ Group: 4 105533 105534 iOS536 105540 105542 105551 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH POTASSIUM SALT (PPOS: T-6295) Ri HGB HCT mev X10'/PC;4L G/DL % FL ---- --- -------- -------- -------- PERFLUOROOCTANE IN CYNOMOLGUS SULFONIC ACID MONKEYS MCH MCHC Py RETIC PG % XIO /mL % -------- -------- ------- x --- Dose Level: 0.75 6.46 6.72 6.67 6.21 6.57 6.35 12.1 13.1 12.1 11.8 12.0 11.7 6.50 .195 6 12.1 .50 6 Dosage unit: mg/kg/day 41.2 44.2 41.7 39.6 42.4 40.0 63.8 65.8 62.6 63.8 64.5 63.0 18.7 19.5 16.2 19.0 18.2 18.5 41.5 1.68 6 63.9 1.14 6 18.7 .50 6 29.3 29.6 29.1 29.8 28.3 29.4 29.2 .52 6 337 438 606 433 492 304 435 100.9 6 .2 .4 .1 .0 .4 .4 .2 .18 6 ANIMAL NUMBER ------ Group. I 105529 105530 105531 105535 105544 105549 MEAN S.D. n Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID W)NKRYS W-PC xi 0 /pL -------- N-SEG X103 IAAL -------- LYIPH X10 liAL -------- 'HO@p X10 /.uL -------- EO@IIN XIO IJAL -------- BASY N-SEGS X10 /jwL -------- -------- LYMPHf6 MONO% EO ----- -------- --- Dose Level: 0 Dosage Unit: mg/kg/day 7.4 3.4 3.3 .6 .2 .0 45 45 a 11.7 6.0 4.9 .7 .1 .0 51 42 6 8.4 5.0 2.6 .7 .1 .1 59 31 8 12.6 5.0 6.0 .8 .6 .1 39 48 7 13.0 5.3 5.8 1.2 .7 .0 40 44 9 0.0 3.1 4.3 .5 .1 .0 38 54 6 10.2 2.52 6 4.6 1.14 6 4.5 1.36 6 .8 .3 .0 .24 .28 OS 6 6 6 45 44 7 8.3 7.6 112 6 6 6 Dose Level: 0.03 Dosage Unit: mg/kg/day 12.2 8.6 6.1 3.0 6.8 3.6 7.6 4.6 8.7 2.41 4 5.0 2.52 4 Dose Level: 0.15 2.7 .6 .2 4.1 .9 .1 2.5 .6 .1 2.4 .5 .1 2.9 .6 .1 .79 .17 .05 4 4 4 Dosage Unitt mg/kg/day .0 70 22 5 .1 36 50 11 .0 53 36 9 .0 60 32 6 .0 55 35 8 .05 14.3 11.6 2.8 4 4 4 4 7.6 2.6 3.6 1.2 .2 .0 35 48 is 12.0 7.4 3.7 .7 .2 .0 62 31 6 7.1 2.6 3.5 .9 .2 .0 36 49 12 14.4 9.4 4.2 .7 .0 .0 65 29 5 11.3 5.4 4.4 .8 .7 .0 48 39 7 8.0 3.3 3.4 .7 .6 .1 41 42 9 10.1 5.1 3.8 .8 .3 .0 48 40 9 2.94 2.01 .40 .20 .27 .04 13.0 8.4 3.8 6 6 6 6 6 6 6 6 6 512 ANIMAL NUMBER ------ Group:.4 105533 105534 105536 105540 105542 I0555i MEAN S.D. N Appendix 4 individual Clinical Hematology Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PE"LUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID N-SEG LY_IPH -MONP EOrtIN BAS9 N-SEG% LYMPH% MONO% go X10 liAL X10'/,UL X10 /jAL X10 /jwL X10'/iAL XIO /,uL -------- -------- -------- -------- -------- -------- -------- -------- -------- --- Dose Level: 0.75 10.0 4.1 13.3 6.9 9.6 4.4 8.9 5.4 8.3 5.9 3.8 2.0 9.0 3.08 6 4.8 1.70 6 Dosage Unit: mg/kg/day 5.1 .7 .0 5.2 .7 .4 3.5 1.3 .3 2.4 .9 .1 2.0 .4 .0 1.2 .5 .0 3.2 .8 .1 1.66 .32 .18 6 6 .0 41 51 7 .0 52 39 6 .1 46 36 14 .0 61 27 10 .0 71 24 4 .0 53 32 14 .0 54 35 9 .04 10.7 9.7 4.2 6 6 6 6 513 Appendix 4 Individual Clinical Hematology Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERPLTIOROOCTANE SULFMIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ ANISO POLY POIK HYPO TOXNEUT -------- -------- -------- -------- -------- Group: 1 105529 105530 105531 105535 105544 105549 DOSE Level: 0 - - - - - - - - - - - Dosage Unit: mg/kgr/day - - - - - - - - - - - - - - - Group: 2 105537 105541 105547 105550 Dose Level: 0.03 Dosage Units mg/kg/day - - - - - - - - - - - - - - - - Group: 3 105532 105538 105539 105545 105548 105552 Dose Level: 0.15 - Dosage Unit: mg/kg/day Group: 4 105533 105534 105536 105540 105542 105551 Dose Level: 0.75 - Dosage Unit: mg/kg/day 514 ANIMAL NMBER Group: 1 105508 105517 105519 105520 105526 105527 MEAN S.D. m Group.- 2 105514 105515 105516 105521 mm S.D. N Group- 3 3:05505 105510 105518 :105523 .105524 IOSS29 MEAN S.D. Appendix 4 Individual Clinical Hematolow Data Males Day 37 26-WEEK CAPSULE koxrCITY STUDY WITH PERFLUOROOCTME SULFMIC ACID POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS MONKEYS Rpc HGB HCT mcv MCH MCHC Pw RSTIC X10 ITAL -------- G/DL -------- t -------- PL -------- PG -------- t -------- X10 /,uL t -------- -------- Dose Level: 0 Dosage Unit: mg/kg/day 6.53 13.0 41.4 63.4 19.9 31.4 369 .1 66..8332 1123..20 4420..79 6579..58 2107..58 30.4 443 .2 6.50 12.1 39.5 60.7 18.6 29.8 30.7 474 644 .3 .1 66..3240 1112..62 3480..66 6624..30 1189..73 3300..01 361745 ..15 6.45 12.4 40.6 63.0 19.1 30.4 486 .2 .2621 .655 1.464 2.764 .697 .658 1176.8 .616 Dose Level: 0.03 Dosage Unit. mg/kg/day 76..3521 1132..05 4427..59 6655..52 1197..02@ 27.2 492 .6 6.35 12.2 39.0 61.4 19.2 29.4 31.2 629 344 .8 .3 7.26 12.2 40.3 55.6 16.0 30.1 665 .0 6.86 .501 12.5 .38 42.4 3.93 61.9 4.61 18.2 29.5 532 .4 4 4 4 1.17 1.69 146.1 .35 4 4 4 4 4 Dose Level: 0.15 Dosage Unit.- mg/kg/day 6.34 12.8 41.3 65.1 20.3 31.1 421 .3 76..2909 1122..73 4421..15 5598..35 1177..67 2390..72 483 .4 6.78 12.6 41.3 60.9 18.5 30.5 498 544 .6 .4 66..3314 1122..13 4319..48 6652..67 1199..51 2390..74 531898 ..32 6..63685 12..527 41..276 622..906 18.8 30.3 476 .4 6 6 6 1.06 6 6 S3 59.6 .14 6 6 6 515 ANIMAL NUMBER ------ Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS: T-6295) IN CYNO14OLGUS MMKEYS ACID RPC Xio /gL -------- HGB G/DL -------- HCT t -------- mcv FL -------- MCH PG -------- MCHC t ------ - P%.7 X10 /jAL -------- RETIC t -------- x --- Dose Level: 0.75 Dosage unit: mg/kg/day 7.03 6.57 6.84 5.80 6.60 6.32 12.3 11.4 12.1 10.9 12.1 12.3 41.0 39.6 41.9 37.1 40.3 41.5 59.3 60.2 61.3 63.9 61.0 65.6 17.4 17.3 17.6 18.8 18.3 19.4 29.9 28.7 28.8 29.5 30.1 29.6 459 .3 69 PA .3 399 .3 490 .4 362 .5 519 .5 6.53 11.8 40.2 61.7 18.1 29.4 383 .4 .431 .57 1.74 2.63 .85 .57 164.3 .10 6 6 6 6 6 6 6 6 516 ANIMAL NUMBER ------ Group: I 105508 105517 105519 105520 105526 105527 MEAN S.D. N Groupt 2 105514 105515 105516 105521 MEAN S.D. N Groupt 3 105505 105510 iossie 105523 105524 105528 MEAN S.D. N Appendix 4 Individual Clinical HeiRatology Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID w@pc XIO /ML N-MG XIO /iiL LlffPH X10 /14L MONP EO.@IN X10 /,wL X10 /,uL BAS9 N-SEG% X10 /jAL LYMPH% MONO% ROS -------- -------- -------- -------- -------- -------- -------- -------- -------- ---- Dose Level.- 0 Dosage Unit: mg/kg/day 5.2 1.8 2.9 7.8 2.5 4.2 .4 .0 .0 34 .9 .0 .2 32 57 9 53 12 7.1 3.5 3.4 .2 .1 .0 49 46 3 6.8 3.5 2.9 4 .0 .0 52 43 5 7.5 4.7 2.2 .3 .2 .0 63 30 4 11.2 7.5 2.8 .9 .0 .0 67 25 8 7.6 3.9 3.1 .5 .0 .0 50 43 7 1.98 2.01 .67 .31 .08 .08 14.4 12.0 3.4 6 6 6 6 6 6 6 6 6 Dose Level- 0.03 Dosage Unit- mg/kg/day 11.9 5.9 5.3 .5 .2 .0 so 44 4 8.0 3.1 4.1 .6 .2 .0 39 51 7 12.1 8.2 3.1 .7 .2 .0 67 25 5 11.0 8.1 2.4 .3 .1 .0 74 22 3 101..989 62..340 31..276 ..157 .2 .0 58 36 5 4 4 4 .05 .00 15.9 14.2 1.7 4 4 4 4 4 4 Dose Level: 0.15 Dosage Unit% mg/kg/day 11.7 9.3 2.0 .2 .3 .0 79 17 2 8.9 5.1 2.9 .7 .0 .0 se 32 a 9.4 3.9 4.6 .9 .0 .0 42 49 9 116..19 73..50 23..66 ..48 ..10 ..10 6530 3327 124 12.4 7.2 3.6 .7 .8 .1 58 30 5 102..006 62..203 3..291 ..264 ..232 ..005 5182.5 3130.4 63.6 6 6 6' 6 6 6 6 6 6 517 ANIMAL NUMBER ------ Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PEITFLUOROOCTANE SULPONIC POTASSIUM SALT 4PFOSi T-6295) IN CYNOMOLGUS MONKEYS ACID W-F N-SEG LY _VPH mong EO.@IN BASG N-SEGS LYMPH% KOHOK go X10 ISAL XIO ImL X10 /j4L X10 /,uL X10 /,uL X10 /jwL -------- -------- -------- -------- -------- -------- -------- -------- -------- --- Dose Level: 0.75 Dosage Unit: mg/kg/day 7.1 3.4 2.9 .7 .1 .0 49 41 9 17.9 13.3 3.9 .7 .1 .1 74 21 4 11.6 8.0 2.8 .4 .3 .0 69 24 4 9.5 5.5 2.4 .5 .1 .1 65 28 6 6.6 3.5 2.4 .7 .0 .0 53 36 10 10.2 6.2 3.0 ..9 .0 .1 61 30 9 10.3 6.6 2.9 .6 .1 .0 62 30 7 4.16 3.69 .52 .18 .11 .05 9.0 7.5 2.7 6 6 6 6 6 6 6 6 6 518 Appendix 4 Individual Clinical Hematology Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ ANISO -------- POLY -------- POIK -------- HYPO -------- TOXNEUT -------- Group: I 105508 105517 105519 105520 105526 105527 Dose Levels 0 - - - - - - - - - - - Dosage Unit: mg/kg/day - - - - - - - - - - Group: 2 105514 105515 105516 105521 Groups 3 105505 105510 105518 105523 105524 105528 Dose - Level% - 0.03 Dose - Levels - 0.15 Dosage Units mg/kg/day - - - - - - - - Dosage Units mgtkg/day - - - - - - - - - - - - Group- 4 Dose Level: 0.75 Dosage Unit: mg/kg/day 105506 - - - - - 105507 - - - - - 105509 - - - - - 105511 - - - - - TOSS12 - - - - - 105522 - - - - - 519 ANIMAL NUMBER ------ Group: I 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group- 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105S39 105545 105548 105552 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID RPC HGB HCT mcv MCH MCHC Py RETIC X10 /ML G/DL t FL PG X10 IJAL % x -------- -------- -------- -------- -------- -------- -------- -------- --- Dose Level: 0 Dosage Unit: mg/kg/day 6.43 12.3 40.4 62.8 19.1 30.5 647 .3 6.51 12.7 42.1 64.7 19.6 30.2 629 .5 6.37 11.6 38.8 60.8 18.1 29.8 439 .2 6.52 11.9 39.1 60.0 18.0 30.0 538 .1 5.78 11.6 37.9 65.6 20.0 30.5 499 .4 6.85 13.3 44.4 64.8 19.5 30.0 475 .5 6.41 12.2 40.5 63.1 19.0 30.2 538 .3 .351 .69 2.42 2.31 .83 .29 84.2 .16 6 6 6 6 6 6 6 6 Dose Level: 0.03 Dosage Unit: mg/kg/day 6.60 10.9 38.1 57.8 16.6 28.7 440 .3 5.70 11.7 40.5 70.9 20.6 29.0 391 .7 6.79 11.6 39.0 57.4 17.0 29.7 417 .1 7.29 13.2 44.7 61.3 18.1 29.6 411 .1 6.60 11.8 40.6 61.8 10.1 29.2 417 .3 .664 .97 2.92 6.28 1.80 .48 23.6 .28 4 4 4 4 4 4 4 4 Dose Level: 0.15 Dosage Unitt mg/kg/day 6.43 11.9 39.5 61.3 18.5 30.1 451 .4 6.40 11.3 38.4 60.1 17.7 29.5 398 .4 6.35 12.0 40.6 63.8 18.9 29.5 406 .1 6.85 12.4 41.2 60.1 18.1 30.1 300 .3 7.09 11.9 39.8 56.1 16.6 29.8 553 .3 6.19 11.4 39.9 62.7 19.5 29.5 478 .2 6.55 11.0 39.7 60.7 18.1 29.7 431 .3 .343 .41 1.06 2.68 .75 .29 85.3 .13 6 6 6 6 6 6 6 6 520 ANIKAL NUMBER Group; 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N AiDpendix 4 individual Clinical Hematology Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKM POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SUtiPONIC ACID MONKEYS RPC XIO /,uL -------- HGB G/DL, -------- HCT -------- mcv FL -------- MCH PG -------- MCHC t -------- ph RETIC X10 IPAL % -------- -------- Dose Level: 0.75 Dosage Unit: mg/kg/day 6.04 11.6 38.0 62.8 19.1 30.5 345 .3 5.91 11.3 39.4 65.0 19.2 29.5 532 .7 6.43 11.7 41.3 64.2 18.3 28.4 531 .2 6.09 11.4 37.1 60.9 18.7 30.8 501 .1 6.66 12.2 41.8 62.8 18.3 29.2 555 .2 6.12 11.1 37.9 62.0 18.2 29.3 351 .5 6.21 11.6 39.1 63.0 18.6 29.6 469 .3 .280 .38 1.96 1.48 .44 .89 95.4 .23 6 6 6 6 6 6 6 6 521 ANIMAL NUMBER ------ Group: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. n Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMDLOUS SULPONIC MONKEYS ACID XL-W0PC/,uL -------- N-@RG X10 IML -------- LVPH XIO /JAL -------- W)Ng XIO /,uL -------- E0.11N X10 liAL -------- BAS9 XIO /,uL -------- N-SEGO -------- LYMPH% -------- HMO -------- EO, --- Dose Level: 0 Dosage Unit: mg/kg/day 9.6 6.2 2.8 .5 .1 .0 65 30 5 12.1 8.3 2.8 1.0 .0 .0 68 23 a 14.6 11.7 1.9 .9 .1 .1 80 13 6 21.4 12.2 5.9 2.4 .7 .2 57 28 11 8.6 2.3 5.2 .7 .3 .0 26 61 8 10.1 5.9 2.8 1.0 .4 .0 so 28 10 12.7 7.8 3.6 1.1 .3 .0 59 30 a 4.75 3.77 1.59 .67 .26 .08 18.2 16.2 2.3 6 6 6 6 6 6 6 6 6 Dose Level: 0.03 Dosage Unit. mg/kg/day 7.7 3.s 2.8 .8 .5 .1 46 36 10 11.5 6.5 3.7 1.1 .2 .0 56 32 10 7.3 5.0 1.7 .5 .1 .0 68 24 7 11.7 7.9 2.8 .8 .2 .0 68 24 6 9.6 5.7 2.8 .0 .2 .0 60 29 8 2.37 1.90 .82 .24 .17 .05 10.6 6.0 2.1 4 4 4 4 4 4 4 4 4 Dose Level: 0.15 Dosage Unit: mg/kg/day 8.0 5.4 2.0 .4 .1 .0 68 25 5 9.4 5.1 3.4 .6 .3 .0 54 36 6 4.4 1.2 2.8 .4 .1 .0 26 63 8 10.0 5.2 3.9 .7 .1 .0 52 39 7 11.7 7.7 3.0 .5 .4 .0 66 26 4 11.2 8.2 2.2 .4 .5 .0 73 19 4 9.1 5.5 2.9 15 .2 .0 56 35 6 2.66 2.48 .72 .13 .18 .00 17.0 15.7 1.6 6 6 6 6 6 6 6 6 6 522 ANIMAL NUMBER ------ Group- 4 105533 105534 105536 105540 105542 105551 MEAN S.D. Appendix 4 Individual Clinical Hematology Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIE)?4 SALT (PFOS; T-6295) IN CYNOMOEGUS SULF0141C ACID WMKEYS xi W0-F/mL -------- N-SEC X10:11JAL -------- Dose Level: 0.75 LYMPH X10311AL -------- MONP X10 /,uL -------- EO IIN X10 /,wL -------- 13AS9 X10 /,uL -------- N-SBG% -------- Dosage Unit: mg/kg/day LYMPH% -------- MONO% -------- E --- 8.8 3.9 4.4 .4 .0 .0 45 so 5 8.8 4.6 3.0 7.6 4.8 2.0 .9 .6 .2 .0 52 34 11 9.7 5.0 3.9 .6 .1 .1 .0 63 .0 51 27 40 8 7 135..70 121..25 12..38 ..44 ..01 ..00 8444 1473 73 82..895 53..319 21..906 ..260 ..108 ..000 5165.1 3153.7 72.7 6 6 6 6 6 6 6 6 6 523 Appendix 4 individual Clinical Hematology Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID ANIMAL MMER ------ ANISO POLY POIK HYPO TOXNEUT -------- -------- -------- -------- -------- Group-. 1 105529 105530 105531 105535 105544 105549 Group: 2 105537 105541 105547 105550 Group: 3 105532 105538 ZOSS39 105545 105548 105552 Group: 4 105533 105534 105536 105540 105542 105551 Dose Level: 0 - - - - - - - - - - Dose Level: 0.03 - - - - - - - - Dose Level: 0.15 - - - - - - - - - - - - Dose - Levelt - 0.75 Dosage unit: mg/kg/day Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day - - - - - - - - - - - - - - - - - - Dosage Unit: mg/k4/day - - - - - - - - - - - - - - - 524 ANIMAL IRMBER ------ Group: 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group- 3 105505 105510 105518 105523 105524 105528 MEAN S.D. Appendix 4 Individual Clinical Hematology Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SUriPONIC ACID POTASSIUM SALT (PFOSI T-6295) IN CYNOMOLGUS MONKEYS RPC HGB HCT mcv MCH MCHC PIT mmic XIO /,uL -------- G/DL -------- t -------- FL -------- PG -------- t -------- XLO'IA&L -------- t -------- --- Dose Levelt 0 Dosage Unit: mg/kg/day 6.66 13.2 42.0 62.8 19.8 31.S 463 .1 66..9239 1122..29 4412..68 6598..90 2107..46 3209..14 423 .5 6.53 12.4 39.9 61.1 18.9 31.0 S24 699 .3 6.10 11.7 38.1 62.4 19.1 30.7 377 .0 .1 6.43 12.5 42.3 65.8 19.4 29.5 644 .7 6..42992 12..553 411..178 633..303 19..295 30.4 522 .3 6 6 6 6 .84 126.9 .27 6 6 6 6 Dose Level: 0.03 Dosage Unit: ag/kg/day 6.86 6.61 6.44 7.44 12.2 12.6 12.0 12.7 6.84 .437 4 12.4 .33 4 Dose Level: 0.15 41.7 42.3 39.4 42.2 60.9 63.9 61.1 56.8 17.7 19.1 18.7 17.1 41.4 1.36 4 60.7 2.92 4 18.2 .91 4 Dosage Unit- mg/kg/day 29.1 29.9 30.6 30.0 29.9 .62 4 438 647 376 684 536 152.1 4 .1 1.0 .4 .0 .4 .45 4 6.47 6.82 13.0 12.4 41.6 40.1 64.2 58.9 20.1 19.2 31.3 450 .5 7.10 12.7 41.5 58.5 17.8 30.9 30.5 499 576 .5 .6 66..5541 1122..76 4402..91 6642..38 19.5 31.0 625 .1 6.19 11.5 38.2 61.8 19.3 18.6 30.0 30.2 520 349 .0 .2 6..6301S 12..552 410..472 621..576 18..987 30.6 504 .3 6 6 6 .50 97.3 .25 6 6 6 6 525 ANIMAL NUMBER ------ Group: 4 105506 105507 105509 105511 105512 IOS522 MEAN S.D. N Appendix 4 individual Clinical HematologY Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERpLUORoOCTANS POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFORIC ACID MONKEYS RPC Xio /jwL -------- HGB G/DL ------- HCT t -------- mcv FL ------- MCH PG -------- MCHC pv RETIC t X10 /.uL t x --- -------- -------- --- Dose Level: 0.75 Dosage Unit: mg/kg/day 7.46 13.1 43.4 58.2 17.6 30.2 53346 .3 .1 6.81 12.1 40.5 59.4 59.8 17.7 17.7 29.8 29.6 480 .5 6.69 5.86 11.9 11.1 40.0 37.6 64.1 18.9 29.5 629 .4 6.90 12.8 41.6 60.3 18.5 3209..73 355896 .0 .4 6.65 12.8 43.8 65.9 19.3 6.73 12.3 41.2 .61.3 18.3 .72 29.8 .52 437 217.8 .3 .19 .516 .75 2.31 3.02 6 6 6 6 6 6 6 6 526 ANIMAL NUMBER ------ Group: I 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 MEAN S.D. N Appendix 4 individual CliniCal Hematology Data males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS WpC N-SEG LITPH -MONP E0.@IN BJksg N-SEG% LYMPH% MONO% zos X10 /,uL -------- XIO'/,wL -------- XIO /,uL X10'/jWL -------- -------- X10 /ML -------- X10 IIAL -------- -------- -------- -------- ---- DoSe Level: 0 Dosage unit: mg/kg/day '7.4 3.7 3.3 .4' .0 .0 49 45 5 .8.0 2.1 4.7 1.0 .1 .1 27. 59 12 6.7 3.1 3.2 .4 .0 .0 46 40 5 8.0 3.8 3.4 .6 .1 .1 48 43 7 6.0 3.2 2.2 .5 .1 .0 52 36 9 7.6 2.4 4.2 .9 .2 .0 31 54 12 7.3 3.0 3.5 .6 .1 .0 42 48 8 .81 .68 .87 .26 .08 .05 10.5 8.2 3.2 6 6 6 6 6 6 6 6 6 Dose Level: 0.03 Dosage Unit: mg/kg/day 8.1 5.0 2.3 .5 .2 .0 62 29 6 10.3 4.6 4.3 1.2 .2 .0 44 42 12 12.1 7.3 3.5 1.1 .1 .0 61 29 9 11.6 7.5 3.4 .5 .2 .0 65 29 4 10.5 6.1 3.4 .8 .2 .0 58 32 8 1.79 1.51 .82 .38 .05 .00 9.5 6.5 3.S 4 4 4 4 4 4 4 4 4 Dose Levelt 0.15 Dosage Unit: mg/kg/day 10.8 8.0 2.3 .2 .3 .0 73 21 2 13.3 8.7 3.7 .7 .1 .0 65 28 6 9.9 3.2 5.8 .8 .1 .0 32 59 8 12.7 7.7 4.5 .4 .1 .0 60 36 3 7.7 3.2 3.4 1.0 .1 .1 41 44 13 16.4 11.1 3.6 1.3 .4 .1 69 22 8 11.8 7.0 3.0 .7 .2 .0 56 35 7 3.02 3.16 1.18 .40 .13 .05 16.3 14.6 4.0 6 6 6 6 6 6 6 6 6 527 ANIMAL NUMBER ------ Group: 4 105506 105507 105509 iossii 105512 105522 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOSI T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID XL-W0PC/,uL -------- N-V, G X10 liAL -------- LYIIPH XlO'ImL -------- MP X10 /,uL -------- RO.@IN X10 /,UL -------- BASG X10 /,UL -------- N-SEG% -------- LYMPH% -------- NM% -------- Ros ---- Dose Level: 0.75 Dosage unit: mg/kg/day 6.5 2.5 3.5 .4 .1 .0 38 54 6 14.6 9.6 3.6 1.0 .2 .2 66 24 7 10.6 6.4 2.8 .7 .6 .1 60 27 7 7.7 4.2 3.0 .4 .1 .0 54 39 5 7.7 3.6 3.5 .6 .0 .0 46 45 8 10.7 5.5 4.3 .7 .2 .0 51 40 6 9.6 5.3 3.4 .6 .2 .0 52 39 6 2.97 2.52 .52 .23 .21 .08 10.0 11.2 1.0 6 6 6 6 6 6 6 6 528 Appendix 4 Individual Clinical Hematology Data Males Day 62, 26-WEEIK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CyNomoLGus SULFMC i4oNyxrs ACID ANIMAL NUMBER ------ ANISO -------- POLY -------- POIX -------- HYPO -------- TOXNEUT -------- Group. 1 105500 105517 105519 105520 105526 105527 Dose Level: 0 - - - - - - - - - - - Dosage Units mg/kg/day - Group: 2 105514 105516 105521 Dose Levelt 0.03 - - Dosage Unit% mg/kgr/day Group: 3 Dose Level: 0.15 Dosage Unitt mg/kg/day 105505 - - - - iossio - - - - 105518 - - - - 105523 - - - - 105524 - - - - roSS28 - - - Group- 4 Dose Level: 0.75 Dosage Unit: mg/kg/day 105506 - - - - 105507 - - - - 105509 - - - - 105511 - - - - IOSS12 - - - - 105522 - - - 529 ANIMAL NUMBER ------ Group: 1 105529 105530 105531 ZOSS35 IOSS44 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 KEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. Appendix 4 rndividual Clinical Hematology Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANZ SULPOMIC ACID POTASSIUM SALT (PPOS; T-629S) IN CYRomoLGUS moNXgyS Rpc X10 /AL -------- HOD G/DL -------- HCT t -------- mcv FL -------- MCH PG -------- MCHC t -------- pw XIO /JAL -------- RETIC % -------- RE xi ---- Dose Level: 0 Dosage Unit: mg/kg/day 6.15 5.93 12.0 12.1 38.4 39.7 62.4 66.8 19.5 31.3 668 .5 6.56 12.1 40.5 61.6 20.3 18.5 30.4 30.0 515 644 .6 .1 74..9012 1121..75 4325..44 7620..14 18.2 30.0 600 .3 6.83 13.4 44.9 65.8 23.4 19.6 32.4 29.8 506 Sol .7 .5 6..27366 12..366 403..227 644..933 19.9 30.6 572 .4 6 6 6 1.07 1.01 74.6 .22 6 6 6 6 6 Dose Level: 0.03 Dosage Unit: mg/kg/day 6.44 5.67 10.9 12.2 37.8 40.5 58.8 71.3 16.9 21.4 20.9 357 .3 6.82 11.9 39.2 57.4 17.4 30.1 30.3 507 548 .7 .6 7.01 12.9 43.4 62.0 18.4 29.7 437 .0 6..45893 12..083 420..329 62.4' 18.5 29.7 462 .4 4 4 4 6.25 4 2.02 4 .67 4 83.8 .37 4 4 Dose Level: 0.15 Dosage Unit: mg/kg/day 96..1634 1117..02 4505..09 6610..23 1 18.9 30.8 306 .1 6.45 12.5 40.4 62.6 17.8 19.3 29.S 30.9 456 374 .6 .0 6.74 6.80 12.2 11.7 40.3 38.4 59.8 56.4 18.0 17.2 30.2 326 .7 6.21 11.6 38.9 62.6 18.6 30.4 29.7 667 486 .3 .5 7.00 1.068 12.0 42.3 60.5 18.3 30.3 436 .4 2.17 6.70 2.31 .76 .57 133.5 .20 6 6 6 6 6 6 6 6 530 ANIMAL NUMBER ------ Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 individual CliniC&l HematOlOgY Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID RPC HGB XIO /,UL G/DL -------- ------- HCT t -------- mcv FL ------- MCH PG -------- MCHC t --- ---- P%.7 RETIC XIO /,uL t x -------- -------- --- Dose Level: 0.75 6.04 5.74 6.72 6.13 6.75 6.32 11.7 11.4 12.2 11.9 12.1 11.7 6.28 .397 6 11.8 .29 6 Dosage Unit: mg/kg/day 39.0 37.9 42.6 39.5 42.6 39.5 64.6 66.0 63.5 64.5 63.0 62.5 19.3 19.8 18.2 19.4 18.0 10.6 40.2 1.96 6 64.0 1.27 6 18.9 .72 6 29.9 30.0 28.7 30.1 28.5 29.7 29.5 .70 6 355 620 622 432 665 333 504 148.3 6 .4 .5 .1 .6 .0 .1 .3 .25 6 531 ANIMAL NUMBER ------ Group: I 105529 105530 105531 10553S 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 IOS550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 62 W-PC X10 IIAL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS: T-6295) IN CYNOKOLGUS SULFONIC MONKEYS ACID N-SEG 3 XIO /,uL LYIPH X10 /IAL -HOUP X10 /14L EO.@IN X10 /,UL BAS9 X10 /jAL N-SEG% LYMPH% Homo% 20 -------- -------- -------- -------- -------- -------- -------- Dose Level: 0 Dosage Unit: mg/kg/day 5.8 2.9 2.2 .5 .1 .0 50 38 9 13.0 7.8 4.5 .5 .1 .0 60 35 4 14.1 9.9 3.0 .9 .2 .1 70 22 6 10.9 3.S 5.4 1.4 .5 .2 32 49 13 10.5 2.9 7.0 .0 .5 .0 27 67 0 12.4 7.9 3.7 .4 .3 .0 64 30 3 11.1 5.8 4.3 .6 .3 .0 so 40 6 2.93 3.08 1.73 .48 .18 .08 17.6 15.9 4.6 6 6 6 6 6 6 6 6 6 Dose Level: 0.03 Dosage unit: mg/kg/day 10.6 5.7 0.3 2.4 7.2 3.7 8.8 5.6 9.7 1.42 4 4.4 1.59 4 Dose Level: 0.15 8.9 5.7 10.6 5.7 6.1 2.2 9.7 4.0 7.1 2.3 10.1 6.0 8.8 1.78 6 4.3 1.75 6 3.4 .8 .5 5.0 .6 .2 2.7 .5 .2 2.4 .7 .1 3.4 .6 .2 1.16 .13 .17 4 4 4 Dosage unitt mg/kg/day 2.3 .7 .1 4.1 .4 .4 3.1 .5 .2 5.0 .5 .2 3.7 .7 .3 3.2 .3 .5 3.6 .5 .3 .93 .16 .15 6 6 6 .1 54 33 .1 29 61 .0 52 38 .0 63 27 .0 so 40 .06 14.5 14.9 4 4 4 0 a 7 a 8 .5 4 .0 64 26 8 .0 sa 39 4 .1 37 51 9 .0 41 51 5 .1 32 52 10 .0 60 32 3 .0 48 42 6 .05 13.1 11.2 2.9 6 6 6 6 532 ANIMAL NUMBER ------ Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLOUS MONKEYS N-gpG LY@IPH -MONP EO.@IN Bjksg N-SEG% LYMPH% MONO% so XIOW-PCIAAL -------- Xio /,UL XIO /,uL -------- -------- X10 /,uL -------- XIO /,uL -------- X10 /.uL -------- -------- -------- Dose Level: 0.75 8.4 18.0 6.7 8.1 10.0 4.8 3.2 12.8 3.9 4.5 6.9 2.1 9.3 5.6 4.59 3.89 6 6 Dosage unit: mg/kg/day 4.8 .4 .0 3.6 1.4 .2 1.8 .7 .2 2.9 .6 .1 2.6 .4 .1 2.3 .3 .1 3.0 .6 .1 1.07 .40 .08 6 6 6 .0 38 57 4 .1 71 20 9 .1 58 27 11 .0 55 36 7 .0 69 27 4 .0 44 48 6 .0 56 36 7 .05 13.2 14.2 2.7 6 6 6 6 533 Appendix 4 individual Clinical Hematology Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ ANISO -------- POLY -------- POIK -------- HYPO -------- TOXNEM -------- Group.- 1 Dose Level: 0 Dosage Unit: mg/kg/day 105529 105530 105531 105535 105544 105549 Group: 2 105537 105541 105547 105550 Group- 3 105532 105539 105539 105545 105548 105552 Group: 4 105533 105534 105536 105540 105542 105551 - - Dose Level: 0.03 - - - - - - - - Dose Level: 0.15 - Dose Level: 0.75 - - - - - - - - - - - - Dosage Unit: mg/kg/day - Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day - - - - - - - - - - - - - - - - - - 534 Appendix 4 individual Clinical Hematology Data ANIMAL NUMBER ------ Group: I 105508 105517 105519 105520 105526 105527 MEAN S.D. N Groupt 2 105514 105515 105516 105521 MEAN S.D. N Group- 3 105505 105510 105518 105523 105524 105528 mm S.D. N Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULFOMIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLR-US WMKEYS ACID Rlw HGB Xio /jAL G/DL -------- ------- HCT lb -------- mcv FL ------- MCH PG -------- MCHC t --- ---- Py RETIC X10 /,uL % x -------- -------- --- Dose Level: 0 6.39 6.21 6.92 6.45 6.01 6.59 12.0 12.8 12.2 12.1 11.5 12.8 6.43 .314 6 12.4 .53 6 Dose Level: 0.03 6.96 6.71 6.43 7.80 12.3 12.8 12.2 13.4 7.00 .628 4 12.7 .55 4 Dose Level: 0.15 6.07 6.64 6.95 6.33 6.48 6.51 12.1 12.2 12..5 12 5 12.4 12.3 6.50 .295 6 12.3 .16 6 Dosage 39.6 41.3 40.7 39.2 37.4 43.8 40.3 2.17 6 unit-. mg/kg/day 62.0 66.6 58.8 60.8 62.3 66.4 20.0 20.7 17.6 18.8 19.2 19.4 62.8 3.11 6 19.3 1.06 6 Dosage unit: mg/kg/day 42.2 42.9 40.4 44.7 60.6 63.9 62.8 56.8 17.7 19.1 19.0 17.0 42.5 1.78 4 61.0 3.13 4 18.2 1.02 4 Dosage Unit: mg/kg/day 39.4 39.6 40.9 40.0 41.9 40.3 40.4 .93 6 64.8 59.6. 58.8 63.2 64.6 61.8 62.1 2.53 6 19.9 18.3 18.0 19.7 19.2 18.8 19.0 .76 6 32.2 31.1 29.9 30.8 30.8 29.3 30.7 1.00 6 29.2 29..9 30 2 30.0 29.8 .43 4 30.7 30.7 30.5 31.2 29.7 30.5 30.6 .49 6 387 406 475 671 384 614 490 124.3 6 389 630 290 741 512 208.8 4 505 487 501 585 555 346 496 82.6 6 .3 .7 .1 .1 .2 .6 .3 .26 6 .3 1.0 1.3 .2 .7 .54 4 1.6 .4 .2 .4 .2 .3 .5 .54 6 535 ANIMAL NUMBER ------ Group: 4 105506 105507 105509 105511 IOS512 105522 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID RPC X10 /jWL ---- --- HGB G/DL ------- HCT -------- mcv FL -------- MCH PG -------- MCHC ------- Py RETIC X10 /,uL % -------- -------- iu x ---- Dose Level: 0.75 Dosage Unit- mg/kg/daY 7.22 13.0 42.6 59.0 19.0 3208..56 52520 .3 .4 6.81 11.9 41.5 61.0 60.2 17.4 17.7 29.4 47S .6 6.37 5.94 11.3 11.2 38.3 38.0 64.0 18.8 29.4 552 .4 76..1438 1122..97 4432..03 6650..32 1189..15 3209..09 359926 ..16 6.66 12.2 41.0 61.6 18.2 .77 29.6 .65 431 198.6 .4 .19 .488 .81 2.23 2.47 6 6 6 6 6 6 6 6 536 ANIMAL NUMBER ------ Group.- 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Males Day'91 WPC XlO'ImL -------- 26-WEEK CAPSULE ToxiCiTy STUDY WITH PERFLUOROOCTME POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID N-SLEG XIO'/t&L -------- LYIPH X10 /,uL -------- No.@p Xio /pL -------- E0.@IN X10 /,uL -------- Bhsy N-SEG% XIO /,uL -------- ------- LYMPH% MONO% -------- -------- EOS ---- Dose Level: 0 6.1 2.3 7.8 2.9 5.9 2.5 5.1 1.7 5.1 1.7 10.2 3.3 6.7 1.99 6 2.4 .64 6 Dose Level: 0.03 6.9 3.5 7.7 2.4 10.6 6.4 8.7 5.3 8.5 1.60 4 4.4 1.79 4 Dose Level: 0.15 8.9 6.2 10.7 6.4 15.8 7.9 8.6 4.3 6.4 2.8 11.4 6.8 10.3 3.21 6 5.7 1.85 6 Dosage Unit: mg/kg/day 3.2 .3 .2 4.2 .6 .1 3.0 .2 .0 2.9 .4 .1 2.8 .4 .1 6.0 .6 .2 3.7 .4 .1 1.24 .16 .08 6 6 6 Dosage Unit.- mg/kg/day 2.6 .6 .3 4.5 .6 .2 3.4 .6 .1 2.7 .6 .1 3.3 .6 .2 .88 .00 .10 4 4 4 Dosage unit: mg/kg/day 2.2 .3 .1 3.2 .9 .1 6.0 1.0 .1 3.7 .4 .1 2.8 .7 .0 3.4 .6 .5 3.7 .6 .2 1.61 .27 .18 6 6 6 .0 .1 .0 .0 .0 .0 .0 .04 6 .0 .0 .0 .0 .0 .00 4 .0 .1 .1 .0 .1 .0 .0 .05 6 38 37 44 34 34 33 37 4.1 6 50 31 60 fil 50 13.9 4 70 60 50 50 44 59 56 9.3 6 52 54 52 57 56 59 55 2.8 6 38 58 32 31 40 12.6 4 25 30 43 43 44 30 36 8.4 6 5 8 3 a 8 6 6 2.1 6 8 8 6 7 7 1.0 4 4 9 6 5 11 6 7 2.6 6 537 ANIMAL NUMBER ------ Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS suLpONIC ACID MONKEYS WPC xlo,/ML -------- N-SEG XJO'/,uL -------- LYIPH X10 IIAL -------- MONP X10 /ML -------- EO@@im X10 /;gL -------- BA@sg N-SEG% X10 IIAL -------- LYMPH% MONO% EOS -------- -------- Dose Level: 0.75 Dosage Unit: mg/kg/day 7.9 3.6 3.5 .6 .1 .0 46 45 7 10.3 5.0 3.9 1.1 .2 .1 48 38 10 9.1' 5.3 2.8 11.5 7.5 3.4 .5 .4 .0 58 31 6 .4 .2 .0 65 30 4 .0 .1 38 so 10 5.3 2.0 2.7 12.3 7.0 4.6 .5 .3 .4 .0 57 37 2 9.4 5.1 3.5 .6 .2 .0 52 38 6 2.56 2.06 .71 .28 .16 .05 6 6 6 6 6 6 9.8 7.8 3.2 6 6 6 538 Appendix A individual CliniCal Hematology Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ ANISO -------- POLY -------- POIK --- ---- HYPO TOXNEUT -------- -------- Group.- 1 Dose Levels 0 Dosage Unit: mg/kg/day 105508 - 105517 - - - - - - 105519 - - - - 105520 - - - -- - 105526 105527 - - - - - Groups 2 Dose Levels 0.03 Dosage Unit: mg/kg/day 105514 105515 105516 105521 Group: 3 105505 105510 105518 105523 105524 105528 Group: 4 105506 105507 105509 105511 105512 105522 - - Dose Level: 0.15 - - - - - - - - - - - Dose Level: 0.75 - - - - - - - - - - - - Dosage unit: no/kg/day - - - - - - - - - - - - - Dosage unit: mg/kg/day - - - - - - - - - - - - - - - - - - 539 ANIMAL NUMBER ------ Group: 1 105529 105530 105531 105535 105544 Z05549 MEAN S.D. N Groupt 2 105537 105541 105547 105550 MEAN S.D. N Group- 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix Individual Clinical Hematology Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOROL(;US MONKEYS RPC HGE HCT HCV MCH MCHC P@%7 RETIC X10 /,uL G/DL FL PG' X10 /,uL x -------- -------- -------- -------- -------- -------- -------- -------- --- Dose Level: 0 Dosage Unit: mg/kg/day 6.13 11.9 38.3 62.5 19.4 31.0 682 .2 6.50 13.0 43.2 66.5 20.0 30.1 556 .3 6.44 12.0 39.2 60.9 18.6 30.5 629 .4 6.71 12.1 40.1 59.9 18.0 30.1 515 .4 5.26 11.3 37.0 70.4 21.5 30.5 446 .3 6.81 13.4 44.1 64.7 19.7 30.4 544 .3 6.31 12.3 40.3 64.1 19.5 30.4 562 .3 .565 .77 2.79 3.90 1.21 .33 e3.6 .00 6 6 6 6 6 6 6 6 Dose Level: 0.03 Dosage Uniti mg/kg/day 6.22 10.6 37.1 59.7 17.0 28.4 492 .5 5.52 12.8 40.8 73.9 23.1 31.3 462 .5 6.49 11.3 37.5 57.8 17.5 30.2 493 .6 6.55 12.2 41.3 63.0 18.6 29.6 422 .3 6.20 11.7 39.2 63.6 19.0 29.9 467 .5 .472 .97 2.18 7.19 2.78 1.21 33.4 .13 4 4 4 4 4 4 4 4 Dose Level.- 0.15 Dosage Unitt mg/kg/day 6.49 12.2 40.0 61.6 19.8 30.6 423 .2 6.70 12.0 40.9 61.0 18.0 29.5 432 .1 6.16 12.1 39.3 63.8 19.7 30.0 394. .3 6.89 12.7 40.9 59.3 18.4 31.1 355 .3 6.59 11.5 37.6 56.9 17.5 30.7 585 .3 6.14 11.7 37.8 61.6 19.0 30.9 461 .1 6.50 12.0 39.4 60.7 18.6 30.6 442 .2 .298 .42 1.44 2.35 .78 .57 78.9 .10 6 6 6 6 6 6 6 6 540 ANIMAL NUMBER ------ Group: 4 T05533 105534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAM POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS Smp@ONIC MCNKzyS ACID RPC HGB xlO*/;jL G/DL -------- -------- Dose Level.- 0.75 HCT t -------- mcv FL -------- MCH. PO -------- Dosage Unit: mg/kg/day MCHC t -------- PkT ReTrc XiolIjAL t -------- -------- 66..0369. 1111..89 4309..18 6652..77 1189..75 2299..78 352280 ..14 66..3457 1112..75 4402..42 6653..26 1189..43 2298..59 559678 .1 6.57 6.07 11.9 11.4 41.6 .3 18.2 28.7 635 .0 37.8 62.3 18.7 30.1 378 .3 6.32 11.9 40.3 63.8 18.8 29.4 504 .210 .36 .2 1.54 1.37 .51 .54 124.1 .15 6 6 6 6 6 61 6 6 x --- 541 ANIMAL NUMBER ------ Group: I 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N 6roup: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Females Day 91 WPC X10 liAL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLOUS SULFONIC ACXD MONKEYS N-SEG xio '/,uL -------- LNPH X10 /,UL -------- MONP Xio /j4L -------- EO,@IN XIO ImL - ------ BASY N-SEG% LYMPH% MONO% EOS X10 /,uL -------- -------- -------- -------- -- Dose Level: 0 6.4 11.1 9.1 11.7 9.1 8.7 3.2 6.2 4.7 3.0 2.8 4.4 9.4 1.89 6 4.0 1.31 6 Dose Level: 0.03 8.3 3.5 10.4 4.4 4.1 1.7 12.0 8.2 8.7 3.42 4.4 2.74 4 Dosage Unit: mg/kg/day 2.6 .5 .1 4.1 .6 .2 3.5 .6 .3 7.1 .8 .7 5.1 .6 .7 3.5 .6 .2 4.3 .6 .4 1.59 .10 .27 6 6 6 Dosage Unit: mg/kg/day 3.0 1.3 .3 4.9 .9 .2 2.0 .3 .1 2.9 .8 .1 3.2 1.22 4 .0 .2 .41 .10 4 4 .0 .0 .0 .1 .0 .0 .0 .04 6 .2 .0 .0 .0 .0 .10 4 so 56 51 26 30 50 44 12.5 6 42 42 41 68 48 13.2 4 41 37 38 61 56 40 46 10.3 6 37 47 de 24 39 11.2 4 8 5 7 7 6 7 7 1.0 6 is 8 8 6 9 3.9 4 Dose Level: 0.15 6.5 3.6 9.5 5.2 8.5 3.3 8.8 4.4 10.2 5.2 8.9 4.9 8.7 1.25 6 4.4 .82 6 Dosage Unit: mg/kg/day 2.4 .3 .1 3.2 .8 .2 4.4 .5 .2 3.5 .7 .1 3.9 .7 .3 3.1 .5 .4 3.4 .6 .2 .69 .18 .12 6 6 6 .0 .0 .0 .0 .0 .0 .0 .00 6 56 55 39 50 51 55 51 6.4 6 37 34 52 40 38 35 39 6.6 6 5 9 6 8 7 6 7 1.5' 6 542 ANIMAL NUMBER ------ Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Females Day 91 XIO /.uL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWE SULFCNIC ACID POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS MONKEYS N- FTEG LITPH -MONP BO@IIN spksg N-SEG% LYMPH% MONO% EOS Xloj/,UL XIO ImL -------- XIO /,UL X10 I)AL -------- -------- X10 /,uL -------- -------- -------- -------- ---- Dose Level: 0.75 Dosage Unit: mg/kg/day 8.2 3.1 4.3 .7 .1 .1 38 .2 .1 48 53 37 8 12 8.5 4.1 3.1 1.0 2.8 2.2 .6 .2 .0 50 38 10 4 150..77 6.5 3.8 ..43 ..10 ..00 6704 3253 3 9.5 7.0 2.2 6.2 4.1 1.7 .4 .1 .0 66 27 6 8.1 4.6 2.9 .6 .1 .0 56 36 7 .05 13.1 10.4 3.5 1.91 1.75 1.02 .26 .08 6 6 6 6 6 6 6 6 6 543 Appendix A Individual Clinical HematologY Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLuoROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ANIMAL NUMBER ------ ANISO -------- POLY -------- POIK -------- HYPO ------- TOXNEUT Group: 1 Dose Level: 0 Dosage Unitt mg/kg/day ACID 105529 105530 105531 105535 105544 105549 Group: 2 105537 105541 105547 105550 Group: 3 105532 105538 105539 105545 105548 105552 Group: 4 105533 105534 105536 105540 105542 105551 Dose Level: 0.03 - - - - - - - - Dose Level: 0.15 - - - - - - - - - - - - Dose - Level: - 0.75 Dosage Unit: mg/kg/day - - - - - - - Dosage Unitt mg/kg/day - - - - - Dosage Unit: mg/kg/day - - - - - - - - - - -- - - - - - 544 ANIMAL NUMBER ------ Group: 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515. 105516 105521 MEAN S.D. N Group: 3 105505 105510 105519 105523 105524 105528 . N EAN S.D. N Appendix 4 Individual Clinical Hematology Data males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS: T-6295) TN CYNOMOLGUS SULFONIC MONKEYS ACID RPC X10 /jwL -------- HOB G/DL -------- HCT -------- mcv MCH FL PG - ------ ---- --- MCHC py RETIC PZ t X10 /,UL t xi -------- -------- -------- ---- Dose Level: 0 6.44 6.54 7.40 6.44 6.28 6.95 12.3 13.1 12.8 12.1 11.7 6.68 .421 6 12.5 .54 6 Dose Level: 0.03 6.80 7.26 6.55 7.71 12.0 13.0 12.4 12.9 7.08 .513 4 12.6 .46 4 Dose Level: 0.15 6.35 7.19 7.53 6.39 6.74 6.50 12.6 12.6 13.2 12.2 12.8 12.2 6.78 .479 6 12.6 .38 6 Dosage unit: mg/kg/daY 39.3 43.3 42.9 38.7 38.6 42.8 40.9 2.28 6 61.0 66.3 58.0 60.1 61.3 61 .6 61.4 2.74 6 19.1 20.0 17.3 18.8 18.7 18.5 18.7 .88 6 Dosage units mg/kg/daY 40.8 44.0 39.6 42.4 41.7 1.91 4 59.9 60.7 60.5 55.0 59.0 2.70 4 17.7 17.9 18.9 16.7 17.8 .90 4 Dosage unit: mg/kg/day 40.5 41.3 43.4 39.8 42.8 40.2 41.3 1.47 6 63.7 57.5 57.6 62.3 63.5 61.9 61.1 2.82 6 19.9 17.5 17.6 19.2 19.1 18.8 18.7 .95 6 31.4 30.2 29.9 31.2 30.5 30.1 30.6 .62 6 29.5 29.5 31.2 30.4 30.2 .82 4 31.2 30.5 30.5 30.8 30.0 30.4 30.6 .40 6 351 379 447 643 354 613 464 131.6 6 389 618 296 630 483 167.0 4 406 496 546 783 515 366 519 1&6.4 6 .2 .4 .0 .1' .7 .2 .26 6 .2 .2 .4 .0 .2 .16 4 .5 .2 .4 .4 .6 .6 .4 .15 6 545 ANIMAL NU14BER ------ Group: 4 @I05506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 Individual Clinical HematolOgY Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH pERpLuoROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC ACID MONKEYS Rpc X10 /,uL -------- HGB G/DL -------- HCT % -------- mcv FL -------- MCH MCHC PG % --------- -------- Pq RETIC RET X10 /,uL t xi ------ - -------- ----- Dose Level: 0.75 7.78 6.93 6.08 6.10 6.38 13.4 11.7 10.3 11.1 12.0 12.1 6.65 .641 6 11.8 1.04 6 Dosage unit: mg/kg/day 45.8 39.3 36.1 37.7 40.4 40.5 59.0 56.7 59.4 61.8 61.2 63.6 17.3 16.8 16.9 18.2 18.2 19.0 40.0 3.32 6 60.3 2.43 6 17.7 .87 6 29.3 29.7 28.5 29.5 29.7 29.9 29.4 .50 6 486 21 373 553 405 552 398 199.1 6 .4 .1 .7 1.1 1.2 .1 .6 .48 6 546 ANIMAL NUMBER ------ Group: 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MMKEYS ACID N-SEG LI@IPH MONP EO@@IN BAS9 N-SEG% LYMPH% MONO% BOS WPC X10 /jAL X103/,uL X10 IML X10 /,uL X10 /,uL X10 /,uL -------- -------- -------- -------- -------- -------- -------- -------- -------- ---- Dose Level: 0 5.3 1.8 6.7 1.7 6.7 2.9 7.8 2.3 5.2 1.6 12.3 5.9 7.3 2.62 6 2.7 1.64 6 Dose Level.- 0.03 10.0 8.9 11.3 9.6 6.2 3..l 6.4 6.8 9.9 1.04 4 5.6 1.70 4 Dose Level: 0.15 11.8 8.6 9.3 5.5 9.7 2.9 13.8 e.3 6.7 1.9 9.2 3.8 10.1 2.44 6 5.2 2.81 6 Dosage Unit: mg/kg/day 2.9 .3 .4 4.5 .4 .0 3.5 .2 .1 4.3 .7 .3 2.9 .6 .1 5.1 1.0 .1 3.9 .5 .2 .91 .29 .15 6 6 6 Dosage unitt mg/kg/day 3.0 .4 .3 4.8 .6 .2 3.8 .9 .2 2.3 .5 .1 3.5 .6 .2 1.08 .22 .08 4 4 4 Dosage unit: mg/kg/day 2.5 .5 .3 3.1 .6 .1 5.9 .8 .1 4.4 .6 .4 4.1 .7 .1 3.9 .8 .6 4.0 1.17 6 .7 .3 .12 .21 6 6 .0 .0 .0 .2 .0 .0 .0 .08 6 .0 .0 .0 .0 .0 .00 4 .0 .0 .1 .0 .1 .1 .0 .05 6 34 25 43 30 32 48 35 8.6 6 62 35 56 70 56 15.0 4 73 59 30 60 28 42 49 18.2 6 54 68 52 55 56 42 54 8.3 6 30 55 34 24 36 13.5 4 21 33 61 32 61 43 42 16.4 6 5 6 3 9 11 8 7 2.9 6 4 7 8 5 6 1.8 4 4 7 9 4 10 a 7 2.5 6 547 ANIMAL NUMBER ------ Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 Individual Clinical HematolOgY Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID wpc N-SEG LYIPH MONP EO@IIN HAS? N-SEG% LYMPH% MONO% Rosi X10 /,uL X10'/,UL X10 /,uL X10 /,uL X10 /,uL xlO liAL -------- -------- -------- -------- -------- -------- -------- -------- -------- ----- Dose Level: 0.75 Dosage unit: mg/kg/day 6.7 2.5 3.6 .5 .1 .0 38 54 7 8.9 3.9 4.4 .5 .1 .0 44 50 5 13.2 10.0 1.8 1.4 .0 .0 76 13 11 5.9 2.2 3.2 .3 .2 .0 37 55 6 7.6 2.2 4.0 1.2 .1 .0 29 53 15 11.6 5.2 4.9 .9 .5 .1 45 42 8 9.0 4.3 3.6 .8 .2 .0 45 44 9 2.87 3.02 1.08 .44 .18 .04 16.3 16.1 3.7 6 6 6 6 6 6 6 6 6 548 Appendix 4 individual Clinical Hematology Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ Group: 1 105508 105517 105519 105520 105526 105527 Group: 2 105514 105515 105516 105521 ANISO POLY POIX HYPO TOXNEUT -------- 7 ------- -------- -------- -------- Dose Level: 0 Dosage Unit: mg/kg/day - - - - - - - - - - Dose Level: 0.03 Dosage Unit: mg/kg/day - - Group: 3 105505 105510 105518 105523 105524 105528 Dose Level: 0.15 - - - - - - - - - - - - Dosage Unit: mg/kg/day - - - - - - - - - - - - - - - - - - Group: 4 105506 105507 105509 105511 105512 105522 D69e Levelt 0.75 - - - - - - - - - - - - Dosage Unitz mg/kg/day - - - - - - - - - - - - - - - - 549 Appendix 4 Individual Clinical Hematology Data ANIMKL NUMBER ------ Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC ACID MONKEYS Rpc X10 /,uL -------- HGB G/DL -------- HCT t -------- mcv FL -------- MCH PG -------- MCHC % -------- pv XIO liAL -------- PETIC % -------- RE xi ---- Group: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 HEM S.D. N Dose Level: 0 5.82 6.31 6.88 7.30 6.25 7.02 11.3 12.5 12.6 12.9 11.6 13.6 6.60 .559 6 12.4 .05 6 Dose Levelt 0.03 6.74 5.74 6.96 7.20 10.9 12.2 11.7 13.1 6.66 .641, 4 12.0 .92 4 Dose Level: 0.15 6.80 6.37 6.59 7.00 6.84 6.39 12.5 11.7 12.3 12.7 11.6 11.9 6.66 .257 6 12.1 .45 6 Dosage Unit: mg/kg/day 36.1 41.0 40.7 42.9 38.7 44.4 61.9 65.1 59.1 58.7 62.0 63.3 19.3 19.8 18.3 17.7 18.6 19.3 40.6 2.96 6 61.7 2.45 6 18.8 .77 6 Dosage Unit: mg/kg/day 38.5 40.3 39.0 43.9 57.0 70.3 56.0 61.0 16.2 21.2 16.8 18.2 40.4 2.44 4 61.1 6.52 4 18.1 2.23 4 Dosage unit: mg/kg/day 40.8 38.5 40.6 41.5 38.3 39.4 60.0 60.5 61.6 59.3 55.9 61.6 18.4 18.4 18.7 18.1 17.0 18.7 39.9 1.31 6 59.8 2.12 6 10.2 .64 6 31.2 30.4 31.0 30.2 30.0 30.5 30.6 .46 6 28.4 30.2 30.0 29.8 29.6 .82 4 30.7 30.4 30.3 30.6 30.3 30.3 30.4 .18 6 609 544 586 469 498 416 526 73.1 6 322 395 450 391 387 52.3 4 424 425 506 326 545 532 460 83.7 6 .2 .5 .1 .0 .7 .7 .4 .31 6 .4 1.5 .1 .5 .6 ..61 4 .7 .4 .3 .0 .2 .2 .3 .24 6 550 ANIMAL NUMBER Group: 4 105533 105534 105536 105540 105542 105551 MEM S.D. N Appendix 4 individual Clinical Hematology Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SMFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RPC HGB HCT mcv FL MCH MCHC P!q RETIC RLP PG X10 /igL t xi X10 /jwL G/DL -------- -------- -------- -------- -------- -------- -------- -------- ---- Dose Level: 0.75 Dosage Unit: Mg/kg/day 6.67 12.2 41.2 61.7 18.4 29.8 320 .3 6.20 12.1 41.4 66.7 19.5 29.3 582 .3 6.07 11.0 36.8 60.7 18.2 30.0 563 .1 5.97 11.5 37.3 62.4 19.2 30.8 491 .0 6.56 11.6 40.0 60.9 17.6 28.9 671 .1 6.51 11.9 40.3 61.9 18.3 29.6 322 .2 6.33 11.7 39.5 62.4 18.5 29.7 492 .2 .288 .44 1.98 2.21 .70 .65 144.0 .12 6 6 6 6 6 6 6 6 551 ANIMAL NUMBER ------ Group: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWE SULFOWIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS "C N-SEG LY@IPH MONP EOFTIN BJksy N-SEG% LYMPH% 140NOt EOS X10 /jAL Xlol/,uL X10 /14L X10 /,uL X10'/;4L XIO /.uL -------- ---------------- -------- -------- ------- ------- -------- -------- ---- Dose Level: 0 8.4 5.1 8.3 1.8 14.5 9.9 8.3 2.4 8.7 2.9 10.0 5.3 9.7 2.44 4.6 2.98 6 Dose Level: 0.03 8.5 6.5 15.9 6.4 4.2 2.2 10.2 3.5 9.3 4.49 4 5.0 3.55 4 Dose Level: 0.15 5.6 2.5 10.6 6.6 6.3 1.1 11.0 5.3 7.6 3.2 7.5 3.4 8.1 2.23 6 3.7 1.98 6 Dosage Unit: mg/kg/day 2.6 .6 .1 5.9 .5 .1 3.9 .7 .1 4.4 1.0 .5 3.9 1.3 .4 3.8 .7 .1 4.1 1.08 6 .8 .2 .30 .18 6 6 Dosage Unit: mg/kg/day 3.0 .9 .4 3.6 .5 .1 2.8 2.6 .1 2.1 .5 .2 2.9 1.1 .2. .62 1.00 .14 a 4 4 Dosage unit: mg/kg/day 2.4 .6 .1 2.9 .8 .3 4.5 .5 .2 4.8 .6 .2 3.1 .8 .4 3.0 .5 .5 3.4 .6 .3 .96 .14 .15 6 6 6 .0 .0 .0 .1 .1 .1 .0 .05 6 .2 .1 .1 .0 .1 .08 4 .0 10 .0 .0 .0 .0 .0 .00 6 60 22 69 28 34 53 44 18.7 6 49 34 64 55 50 12.6 4 45 63 18 48 42 45 44 14.5 6 31 70 26 52 45 38 44 15.9 6 35 56 18 34 36 15.6 4 43 27 71 44 41 40 44 14.4 6 7 6 5 12 15 7 9 3.9 6 10 8 16 9 11 3.6 4 10 7 8 5 11 7 a 2.2 6 552 ANIMAL NUMBER ------ Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS WpC XI-0 /.uL -------- N-SEG X10'/,uL -------- LY_VPH X10 /,uL -------- MONP EO.@IN X10 /jAL X10 liAL -------- -------- BAS9 XIO /,uL -------- N-SEG% -------- LYMPH% -------- MONO% -------- EOS ---- Dc3se Level: 6.75 Dosage Unit: mg/kg/day 8.2 2.1 4.9 .9 .2 .1 26 60 11 13.2 3.8 7.9 1.0 .4 .1 29 60 7 10.1 6.6 1.9 1.3 .2 .1 65 19 13 11.7 7.4 3.5 .6 .1 .0 64 30 5 9.0 5.0 3.6 .3 .2 .0 55 39 3 4.6 1.7 2.2 .6 .0 .0 38 48 13 9.5 2.99 6 4.4 2.33 6 4.0 2.19 6 .8 .2 .0 46 43 9 .35 .13 .05 17.4 16.5 4.3 6 6 6 6 6 6 553 Appendix 4 Individual clinical Hematology Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ANIMAL NLR4BER ------ ANISO POLY -------- -------- POIK HYPO -------- -------- TOXNEUT -------- Group: 1 Dose Level: 0 Dosage Unit: mg/ko/day 105529 105530 105531 105535 105544 105549 Groupt 2 105537 105541 105547 105550 Group: 3 105532 105538 105539 105545 105548 105552 Dose Levelt 0.03 - - - - - - - - Dose Level: 0.15 - - - - - - - - - - - Dosage unit: mg/kg/day - Dosage Unit: mg/kg/day Group: 4 105533 105534 iOS536 105540 105542 105551 Dose Level: 0.75 - - - - - - - - - - - Dosage unit: mg/kg/day - - - - - - - - - - - - - - - 554 AN114AL NU1413ER Group: 1 105508 105517 105519 105520 105526 105527 MEAN S.X). N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group- 3 105505 105510 105518 10!5523 105524 105528 MEA.N S.D. N Appendix 4 Individual Clinical Hematology Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID RPC X10 /,wL -------- HGB G/DL -------- HCT t -------- mcv FL -------- MCH PG -------- MCHC t -------- pw RETIC X10 /jiL t -------- -------- RE xi ---- Dose Level: 0 6.43 6.72 7.22 6.17 6.48 6.57 12.8 13.1 12.7 11.7 12.2 12.3 6.60 .354 6 12.5 .50 6 Dose Level: 0.03 6.88 6.47 6.61 7.86 12.1 12.2 12.5 13.1 6.96 .627 4 12.5 .45 4 I)ose Level: 0.15 6.43 6.98 7.21 6.50 6.57 6.21 12.5 12.4 12.8 12.6 12.6 11.9 6.65 .372 6 12.5 .31 6 Dosage Unit: mg/kg/day 40.3 44.2 42.0 38.0 40.4 41.7 62.7 65.8 58.1 61.6 62.3 63.5 19.9 19.5 17.6 18.9 18.8 18.8 41.1 2.07 6 62.3 2.53 6 18.9 .78 6 Dosage Unit: mg/kg/day 42.5 40.7 40.8 44.5 61.7 62.9 61.7 56.6 17.6 18.8 18.9 16.7 42.1 1.79 4 60.7 2.81 4 18.0 1.05 4 Dosage Unit.- mg/kg/day 41.8 40.8 42.1 40.7 41.8 39.0 65.0 58.4 58.4 62.6 63.5 62.9 19.5 17.8 17.7 19.3 19.2 19.1 41.0 1.15 6 61.8 2.76 6 18.8 .80 6 31.7 29.6 30.2 30.7 30.2 29.6 30.3 .79 6 28.5 29.9 30.6 29.5 29.6 .88 4 30.0 30.4 30.4 30.9 30.2 30.4 30.4 .30 6 404 399 445 591 392 571 467 90.4 6 398 559 246 663 466 183.0 4 411 464 514 526 527 380 470 63.1 6 .1 .2 .2 .1 .1 .3 .2 .09 6 .4 .2 .0 .1 .2 .17 4 .3 .3 .3 .3 .2 .3 .3 .04 6 555 AN]IMAL NUt4BER Group: 4 105506 a 105507 105511 105512 105522 MEAN S.D . N Appendix 4 individual Clinical Hematology Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID Rpc X10 /,uL -------- HGB G/DL -------- HCT t -------- mcv FL -------- MCH PG -------- MCHC t -------- Py RETIC XIO /,uL t -------- -------- RE xi ---- Dose Level: 0.75 7.69 6.64 5.76 6.46 6.44 13.3 11.0 10.4 11.7 12.3 6.32 .387 4 11.4 .83 4 Dosage unit: mg/kg/day 44.3 38.4 35.7 39.8 41.5 57.7 57.9 62.0 61.6 64.5 17.2 16.5 18.1 18.1 19.1 38.8 2.45 4 61.5 2.72 4 17.9 1.08 4 29.9 28.5 29.2 29.4 29.6 29.2 .48 4 560 .2 78 PA .3 486 .5 429 .0 610 .0 401 .2 228.0 .24 4 4 a Unscheduled sacrifice on Day 179. 556 ANIMAL NUMBER ------ Group: 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group- 3 105505 105510 105518 105523 105524 105528 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS WPC N-@@EG LITPH MONP EO@IN BAS9 N-SEG% LYMPH% MONO% BOS X10 /,uL X10 /,uL X10 /,uL X10 /PL X10 /,uL X10 /,uL -------- -------- ---------------- -------- -------- -------- -------- ------------ Dose Level: 0 Dosage Unit: mg/kg/day 9.5 3.6 4.9 .6 .5 .0 38 50 6 9.0 2.6 5.6 .6 .1 .1 30 62 7 6.9 4.0 2.5 .3 .1 .0 58 37 4 12.0 5.8 5.0 .7 .4 .1 49 42 6 10.0 6.7 2.9 .4 .1 .0 67 28 4 10.0 2.8 6.0 1.6 .3 .1 26 55 15 9.7 4.2 4.4 .7 .2 .0 45 46 7 1.76 1.66 1.46 .46 .18 .05 16.1 12.4 4.1 6 6 6 6 6 6 6 6 6 Dose Level: 0.03 Dosage Unitt mg/kg/day 8.9 5.7 2.6 .4 .2 .0 64 30 4 7.5 2.7 3.6 .9 .2 .0 36 48 12 8.1 5.8 1.9 .3 .1 .0 71 23 4 9.1 5.2 3.2 .6 .1 .0 58 35 6 8.4 4.8 2.8 .6 .2 .0 57 34 6 .74 1.46 .74 26 .06 .00 15.1 10.6 3.8 4 4 4 4 4 4 4 a 4 Dose Level: 0.15 Dosage Unit: mg/kg/day 10.3 7.5 2.3 .4 .2 .0 72 22 4 9.1 4.6 3.9 .4 .1 .0 51 43 5 13.6 6.6 6.6 .3 .1 .0 48 48 2 10.8 6.3 3.8 .5 .1 .0 59 35 5 6.1 1.6 3.8 .5 .1 .0 26 63 9 10.0 4.6 4.1 .7 .6 .0 46 41 7 10.0 5.2 4.1 .5 .2 .0 50 42 s 2.44 2.10 1.39 .14 .20 .00 15.2 13.6 2.4 6 6 6 6 6 6 6 6 6 557 ANIMAL NUMBER Group: 4 105506 a 105507 105511 105512 105522 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data wpc X10 ImL Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS N-SEG Xlol/,UL -------- LYIPH X10 /,UL -------- MONP X10 /ML -------- EO.@IN X10 /jWL -------- BAS9 N-SEG% X10 /,uL -------- -------- LYMPH% -------- MONO% -------- gos ---- Dose Level: 0.75 19.7 9.4 5.1 6.6 9.2 14.7 3.9 2.0 1.9 3.9 7.6 2.09 4 2.9 1.13 4 Dosage Unit: mg/kg/day 4.0 1.0 .0 4.9 .4 .1 2.3 .6 .2 4.3 .4 .0 4.5 .6 .2 4.0 .5 .1 1.16 .12 .10 4 4 4 .0 74 20 5 .0 42 52 5 .1 39 45 11 .0 28 66 s .1 43 49 6 .0 38 53 7 .06 6.9 9.1 2.9 4 4 4 4 a Unscheduled sacrifice on Day 179. 558 Appendix 4 individual Clinical Hematology Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NU14BER ------ ANISO POLY POIK HYPO TOXNEUT -------- -------- -------- -------- -------- Group: 1 105508 105517 105519 105520 105526 105527 Group: 2 105514 105515 105516 b 105521 Group: 3 105505 105510 105518 105523 105524 105528 Group: 4 105506 a 105507 105511 105512 105522 Dose Level: 0 - - - - - - - - - - - - DoSe Level: 0.03 - - - - - - - - Dose Level: 0.15 - - - - - - - - - - - Dose Level: 0.75 - - - - - - - - - - Dosage Unit: mg/kg/day Dosage Unit: mg/kg/daY - - - - - - - - Dosage unit: mg/kg/d&Y - - - - - - - - - - - - - - - Dosage Unit: mg/kg/day - - - - - - - - - - - - - - a unscheduled sacrifice on Day 179. b Plasmodium was observed. 559 ANIIIAL NUMBER Grou]p: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group.- 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID RPC X10 /,uL -------- HGB G/DL -------- HCT -------- mcv FL -------- MCH PG -------- MCHC -------- PIF X10 /.uL -------- RETIC % -------- Rlr, xi ---- Dose Level: 0 Dosage Unit: mg/kg/day 5.66 11.0 35.7 63.0 19.5 31.0 595 .2 6.38 12.6 42.6 66.8 19.7 29.6 583 .4 6.63 12.0 40.5 61.2 18.1 29.5 534 .3 7.04 12.7 42.8 60.8 18.1 29.7 369 .2 6.20 11.9 40.9 65.9 19.2 29.1 439 .0 6.52 12.5 42.3 64.9 19.2 29.6 383 .6 6.40 12.1 40.8 63.8 19.0 29.7 484 .4 .461 .64 2.67 2.49 .70 .65 100.1 .24 6 6 6 6 6 6 6 6 Dose Level: 0.03 Dosage Unit: mg/kg/day 6.69 10.8 38.9 58.2 16.2 27.9 442 .2 5.80 12.2 41.4 71.3 21.1 29.5 380 .2 5.20 9.0 30.1 58.0 17.4 30.0 501 .4 6.92 12.7 42.7 61.8 18.3 29.7 394 .1 6.15 11.2 38.3 62.3 18.2 29.3 429 .2 .798 1.66 5.67 6.23 2.09 .94 54.7 .13 4 4 4 4 4 4 4 4 Dose Level: 0.15 Dosage unit: mg/kg/day 6.65 12.3 40.8 61.3 18.4 30.1 373 .3 6.14 11.0 37.6 61.2 17.9 29.3 381 .3 6.67 12.5 41.9 62.7 18.8 29.9 400 .2 6.91 12.4 41.0 60.3 18.3 30.3 318 .0 6.75 11.3 37.8 56.1 16.8 30.0 484 .2 6.38 11.9 40.2 63.0 18.7 29.7 517 .1 6.57 11.9 39.9 60.8 18.2 29.9 412 .2 .256 .62 1.78 2.50 .73 .35 74.4 .12 6 6 6 6 6 6 6 6 Appendix 4 individual Clinical Hematology Data Females Day 182 ANIIKAL NUMBER 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS RPC HGB HCT mcv MCH MCHC pw RETIC PX X10 /,uL % xi XIO /tiL -------- GIDL -------- t FL -------- -------- PG -------- -------- -------- -------- Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day 105533 105534 105536 105540 105542 105551 6.00 11.3 37.6 62.6 18.9 30.1 286 .2 5.65 11.0 37.7 66.8 19.4 29.1 587 .5 6.08 10.9 39.3 64.6 17.9 19.3 27.8 29.9 559 454 .0 .0 5.99 6.75 11.6 11.9 38.6 43.4 64.5 64.3 17.7 27.5 725 .4 6.09 11.3 38.4 63.1 10.6 29.5 328 .1 MEAN S.D. N 6.09 11.3 39.2 64.3 18.6 29.0 490 .2 .360 .37 2.17 1.46 .71 1.09 166.0 .21 6 6 6 6 6 6 6 6 561 ANIMAL NUMBER ------ Group: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 individual Clinical HematolOgY Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC ACID MONKEYS WPC N-REG LY@IPH X10 /,uL X10'/,uL X10 /,uL -------- -------- ----7 --- MONP EO.IIN BAS9 N-SBG% X10 /,uL X10 /,uL X10 /,uL -------- -------- ---- --- ------- LYMPH% W)NO% EOS -------- -------- ---- Dose Level: 0 Dosage Unit: mg/kg/day 14.6 11.4 2.5 .6 .1 .1 78 17 4 7.3 2.6 3.9 .6 .2 .0 35 54 a 10.5 5.2 4.3 .7 .2 .1 50 41 7 13.9 5.5 7.0 1.0 .3 .1 39 50 7 10.4 2.9 6.2 .6 .6 .0 28 60 6 5.4 2.4 2.1 .7 .1 .0 44 40 14 10.4 5.0 4.3 .7 .2 .0 46 44 8 3.59 3.41 1.96 .15 .19 .05 17.5 15.1 3.4 6 6 6 6 6 6 6 6 6 Dose Level: 0.03 Dosage Unit: mg/kg/day 10.1 5.4 3.1 1.1 .4 .2 54 30 11 6.6 2.4 3.5 .5 .2 .0 37 53 7 6.8 4.0 2.4 - .4 .1 .0 so 35 6 10.4 5.5 3.7 .8 .4 .0 53 35 7 8.5 4.3 3.2 .7 .3 .0 50 38 6 2.05 1.45 .57 .32 .15 .10 9.3 10.1 2.2 a 4 4 4 4 4 A 4 4 Dose Level: 0.15 Dosage Unit: mg/kg/day 8.2 3.9 3.8 .4 .1 .0 48 46 5 9.2 4.5 3.8 .6 .3 .0 49 41 6 7.5 1.6 4.9 .8 .1 .1 22 65 10 11.0 6.3 3.9 .6 .1 .0 57 36 6 11.3 6.2 3.7 .6 .7 .0 55 33 5 8.0 4.3 3.0 .3 .4 .0 54 37 4 9.2 4.5 3.8 .6 .3 .0 48 43 6 1.61 1.73 .61 .18 .24 .04 13.0 11.7 2.1 6 6 6 6 6 6 6 6 6 562 ANIMAL NUMBER Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 individual Clinical Hematology Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT JPFOS, T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID wpc N-SEG LYMPH MONP EortiN BAS9 N-SEG% LY14PH% MONO% EOS xio /,uL Xlol/,UL Xlol/,uL XIO /,uL X10'/mL XIO /,uL -------- -------- -------- - ------ ---- --- -------- -------- ------7- Dose Level: 0.75 Dosage Unit: mg/kg/day 7.5 3.2 3.8 .4 ..12 ..11 4412 5419 50 12.1 5.0 6.0 1.0 8.4 4.1 2.8 1.2 .2 .1 49 34 14 10.3 5.9 3.8 .5 .1 .0 58 37 5 13.4 3.0 9.3 .8 .3 .1 22 69 6 6.4 4.0 1.8 .5 .1 .0 63 28 8 9.7 4.2 4.6 .7 .2 ..105 4164.6 4154.8 a3.4 2.73 1.10 2.70 .32 .08 6 6 6 6 6 6 6 6 6 563 Appendix 4 individual Clinical Hematology Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOSs T-6295) IN CYNOMOLGUS SU16FONIC ACID MONKEYS ANIMAL NUMBER ------ ANISO -------- POLY -------- POIX -------- HYPO -------- TOXNEUT -------- Group: 1 105529 105530 105531 105535 105544 105549 Group: 2 105537 105541 105547 105550 Group: 3 105532 105538 105539 105545 105548 105552 Dose Level: 0 - - - - - - - - - - - - Dose Level: 0.03 - - - - - - - - Dose Level: 0.15 - - - - - - - - - - - - Dosage Unit: mg/kg/day - - - - - - - - - - - - - - Dosage Unit: mg/kg/day - Dosage unit: mg/kg/day - - - - - - - - - - - - - - - Group: 4 Dose Level: 0.75 Dosage unit: mg/kg/day 105533 105534 105536 105540 105542 105551 564 ANIMAL NUMBER ------ Group: I 105520 105526 MEAN S.D. Croup- 3 105505 105523 HEM S.D. N Group: 4 105511 ZOSS22 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Nales Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS: T-6295) IN CYHOMOLCUS RBC XIO'/)iL -------- HGB G/DL -------- HCT t -------- mcv FL -------- MCH PG -------- MCHC % -------- PLT X10@/jiL -------- RETIC. % -------- RETI, xio ------ Dose Level: 0 Dosage Unit: mg/kg/day 6.27 12.1 38.3 61.0 19.3 31.7 620 .3 6.26 11.8 37.9 60.5 18.9 31.2 346 .4 6.26 12.0 38.1 60.8 19.1 31.5 483 .4 .007 .21 .28 .35 .28 .35 193.7 o7 2 2 2 2 2 2 2 2 Dose Level: O.IS Dosage Unit: mg/kg/day 6.53 13.0 41.6 63.7 19.9 31.3 404 .4 6.45 12.4 39.8 61.8 19.3 31.2 572 .2 6.49 12.7 40.7 62.8 19.6 31.2 488 .3 .057 .42 1.27 1.34 .42 o7 118.8 .14 2 2 2 2 2 2 2 2 Dose Level: 0.75 Dosage Unit: mglkg/day 5.93 11.6 38.2 64.S 19.5 30.3 485 .3 5.87 11.5 37.3 63.5 19.6 30.9 453 .6 5.90 11.6 37.8 64.0 19.5 30.6 469 .4 .042 .07 .64 .71 .07 .42 22.6, .21 2 2 2 2 2 2 2 2 ANIMAL NUMBER ------ Group: 1 itiSS20 1115526 MEAN S.D. 11 Group: 3 I05sos IfISS23 MEAN S.D. Group: 4 105511 1115522 MEAN S.D. N APPENDIX 4 Individual Clinical HeMatology Data males Day 217 WBC XIO'/itL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAIIE SULFONIC ACID POTASSIUM SALT (PFOS; T-629S) IN CYNOMOLCUS N-SEG X10*/isL -------- LY14PH X10'/ojL -------- mono EOSIN 5(10'lstL XIO'/j4L -------- -------- BASO 1;-SEG% LYMPH% MONO% EOSII X10.'/;iL ----- -- -------- -------- -------- ----- Dose Level: 0 9.5 2.5 6.1 2.3 7.3 1.70 2 2.4 .14 2 Dosage Unit: mg/kg!dal, 5.2 s .3 2.9 .7 .2 4.0 1.63 2 .6 .2 .14 o7 2 2 .0 30 61 6 .0 37 47 12 .0 34 54 9 .00 4.9 9.9 4.2 2 2 2 2 Dose Level: O.lS Dosa@ie Unit: mg/kgiday 8.8 4.7 3.u .7 .4 .0 53 34 14.2 7.6 6.0 .4 .2 .0 53 42 3 11.5 6.2 4.5 .6 .3 .0 53 38 6 .00 .0 5.7 3.S 3.82 2.05 2.12 .21 .14 2 2 2 2 2 2 2 2 2 Dose Level: 0.7S Dosace Unit: mg/kg/day 8.9 4.1 3.9 .5 .4 .0 46 44 14.7 7.9 5.0 1.3 .5 .0 54 34 9 11.8 6.0 4.4 .9 .4 .0 so 39 7 4.10 2.69 .78 .57 .07 .00 S.7 7.1 2.8 2 2 2 2 2 2 2 2 2 APPENDIX 4 individual clinical Hematology Data Hales Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE-SULFONIC POTASSIU14 SALT (PFOS: T-629S) IN CYNO@IOLGUS ACID ANIMAL IJUHBER ------ ANISO -------- POLY -------- POIK -------- HYPO -------- TOXNEUT -------- Group: 1 105520 iOSS26 Group: 3 10550S iOS523 Group: 4 105511 105522 Dose Level: 0 - Dose Level: O.IS - Dose Level: 0.75 - Dosage Unit: mg/kg!day Dosage Unit: mo/kgiday Dosage Unit: mg/kg/day ANIMAL NUMBER Group: 1 11)5529 105549 HEAIJ S.D. Groi.sp: 3 105539 105SS2 HEAII Group: 4 105533 105542 MEAff S.D. N APPENDIX 4 individual clinical Hematology Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAIIE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOTIOLCUS R13C X10'/IjL -------- HGB G/DL -------- HCT 'k -------- mcv FL -------- MCH PC -------- 14CHC t -------- PLT X10'/ML -------- RETIC t - ------ RETI xio ----- Dose Level: 0 Dosage Unit: mg/kolday 5.44 10.9 33.5 61.5 20.1 32.7 S47 .1 6.45 12.6 40.3 62.4 19.6 31.3 390 .5 5.94 11.8 36.9 62.0 19.8 32.0 468 .3 .714 1.20 4.81 .64 .35 .99 111.0 .28 2 2 2 2 2 2 2 2 Dose Level: 0.15 Dosage Unit: mg/kg/day 6.07 11.8 37.2 61.4 19.5 31.8 382 .2 6.20 12.0 38.0 61.3 19.4 31.6 435 s 6.14 11.9 37.6 61.4 19.5 31.7 408 .4 .092 .14 .57 .07 .07 .14 37.S .21 2 2 2 2 2 2 2 2 Dose Level: 0.75 Dosage unit: mg/kg/day 6.13 11.8 38.2 62.2 19.2 30.8 330 .3 6.72 12.2 42.3 63.0 18.2 29.9 557 .7 6.42 12.0 40.2 62.6 28.7 29.8 444 .5 .417 .28 2.90 .57 .71 1.34 160.S .28 2 2 2 2 2 2 2 2 ANIMAL NUMBER ------ Group: I 11)5529 11)5549 MENI S.D. Groijp: 3 IUSS39 IU5552 MEAN S.D. if Group: 4 105533 iOSS42 HEM r..D. N APPENDIX 4 individual clinical Hematology Data Females Day 217 WBC X10'/@#L -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SEIG Xio /itL LYM-PH M0140 XIO @'/i#L klO'li4L EOSI- N XIO @'/itL BASO N-SEG% X10@ liel -------- -------- -------- -------- -------- -------- LYNPH% -------- t-lotio% -------- EOSI ----- Dose Level: 0 Dosage Unit: nig!kg/day 10.1 6.1 3.0 .8 .1 .0 60 30 6.2 3.1 2.S .4 .1 .0 so 41 7 8.2 4.6 2.8 .6 1 .0 ss 36 a 2.76 2.12 .3c@ .28 .00 .00 7.1 7.8 .7 2 2 2 2 2 2 2 2 2 Dose Level: O.lS Dosage Unit: ntgll-.g/day 6.9 1.8 4.3 .7 .2 .1 26 61 10 8.4 3.5 3.8 .5 .5 .0 41 4S 6 7.6 2.6 4.0 .6 .4 .0 34 53 1.06 1.20 .35 .14 .21 .07 10.6 11.3 2.8 2 2 2 2 2 2 2 2 2 Dose Level: 0.7S 7.7 2.1 10.9 3.0 9.3 2.26 2 2.6 .64 2 Dosage Unit-. mg/kg/day 5.0 .3 .3 6.7 .8 .2 5.8 .6 .2 1.20 .35 o7 2 2 2 .0 27 @s 4 .1 28 62 8 .0 28 64 6 .07 .7 2.1 2.9 2 2 2 2 APPENDIX 4 individual Clinical Hematology Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULF01ilC ACID POTASSIUM SALT (PFOS; T-629S) IN CYIIOMOLGUS A141MAL TIUMBER ------ ANISO -------- POLY -------- POIK -------- HYPO -------- TOXIIELIT -------- Group: I IOSS29 IOSS49 Group: 3 105539 105552 Group: 4 Dose Level: 0 - Dose Level: 0.15 - Dose Level: 0.75 Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day 105533 - 105542 - ANIMAL NUMBER Group: 1 105520 IOSS26 MEAII S.D-. N Group: 3 rossos 105523 MEAN S.D. N Group: 4 105511 105522 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC XIO'/,uL -------- HGB HCT G/DL --------* -------- mcv FL -------- MCH PG -------- MCHC -------- PLT X10'/;4L -------- RLpric -------- RET xio ----- Dose Level: 0 6.75 6.28 13.0 12.2 6.52 .332 2 12.6 .57 2 Dose Level: 0.15 6.75 6.82 13.3 13.3 6.78 .049 2 13.3 .00 2 Dose Level: 0.75 6.06 6.33 11.4 12.4 6.20 .191 2 11.9 .71 2 Dosage Unit: mg/kg/day 40.6 37.9 60.2 60.3 19.3 19.4 39.2 1.91 2 60.2 .07 2 19.4 .07 2 Dosage Unit: mg/kg/day 42.5 41.8 62.9 61.3 19.8 19.4 42.2 .49 2 62.1 1.13 2 19.6 .28 2 Dosage Unit: mg/kg/day 39.0 39.9 64.4 63.0 18.8 19.5 39.5 .64 2 63.7 .99 2 19.2 .49 2 32.1 32.1 32.1 .00 2 31.4 31.7 31.6 .21 2 29.2 31.0 30.1 1.27 2 685 428 556 181.7 2 467 519 493 36.8 2 501 562 532 43.1 2 .1 .3 .2 .14 2 .1 .2 .2 .07 2 .8 .4 .6 .28 2 ANIMAL NUMBER ------ Group: I IOSS20 105526 mmi S. D. Group-. 3 iossos 105523 KEAN s.D. N Group: 4 105SIl 105522, MEAN S.D. N APPENDIX 4 individual Clinical Hematology Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS WBC N-SEG LYMPH J40NO EOSIII BASO -X-l-o---'/-I-i-L --Xl-o-'-/-i-j-L X10'/oiL -------- XIO'lo4L -------- X10'/jwL X10'/,wL -------- ------ - N-SEG% LYMPH% MON096 EOSI -------- -------- -------- ----- Dose Level: 0 12.1 8.0 3.8 2.7 10.0 2.90 3.2 .78 2 Dose Level: 0. 15 10.6 12.2 5.2 S.8 1.1.4 1.13 2 5.5 .42 2 Dose Level: 0.75 9.5 17.3 3.6 7.6 13.4 5.52 2 5.6 2.83 2 Dosage Unit: mg/kg/day 7.6 4.6 6.1 2.12 2 .5 .4 .4 .07 2 .3 .3 .3 .00. 2 Dosage unit: mg/kg/day 4.1 S.6 .8 .4 .4 .3 4.8 1.06 2 .6 .4 .28 .07 2 2 Dosage unit: mg/kg/day 4.9 7.4 6.2 1.77 2 .6 1.5 1.0 .64 2 .4 .6 .5 .14 2 .0 .0 .0 .00 2 .0 .0 .0 .00 2 .1 .1 .1 .00 2 31 33 32 1.4 2 49 48 48 .7 2 38 44 41 4.2 2 63 58 60 3.S 2 39 46 42 4.9 2 51 43 47 5.7 2 4 5 4 .7 2 8 3 6 3.5 2 6 9 8 2.1 2 APPENDIX 4 individual Clinical Hematology Data Hales Day 24S 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFonrc ACID POTASSIUM SALT IPFOS: T-6295) IN CYNOMOLGUS ANIMAL TIUMBER ------ A141SO -------- POLY -------- POIK -------- HYPO -------- TOXNEUT -------- Group: 1 IOSS20 IOSS26 Group: 3 105505 105523 Group: 4 105511 105522 Dose Level: 0 - Dose Level; 0.15 - Dose Level: 0.75 - Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day APPENDIX 4 ANIMAL NUMBER ------ Group: I 105529 105549 MEAFJ S.D. N Group: 3 105539 105552 MEAN S.D. N Group: 4 IOSS33 iOSS42 ME" S.D. N individual Clinical Hematology Data Females t)ay 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYI;OMOLGUS RBC X10, /JJL -------- HGB C/DL -------- HCT t -------- mcv FL -------- MCH PG -------- MCHC t -------- PLT X10'/i#L -------- RETIC t -------- RETI xio@ ------ Dose Levol: 0 5.70 6.74 11.3, 13.3 6.22 .735 2 12.3 1.41 2 Dose Level: 0.15 6.88 6.61 12.9 12.5 6.74 .191 2 12.7 .28 2 Dose Level: 0.7S 6.38 7.02 12.2 12.8 6.70 .453 2 12.S .42 2 Dosave Unit: mg/kg/day 34.9 41.9 61.1 62.1 19.8 19.7 38.4 4.95 2 61.6 .71 2 19.8 .07 2 Dosage Unit: mg/kg/day 40.9 40.4 59.4 61.2 18.7 18.9 40.7 .3S 2 60.3 1.27 2 18.8 .14 2 Dosage Unit: mg/kg/day 39.9 44.1 62.S 62.8 19.2 18.2 42.0 2.97 2 62.7 .21 2 18.7 .71 2 32.4 31.7 32.1 .49 2 31.4 31.0 31.2 .28 2 30.7 29.0 29.8 1.20 2 577 461 519 82.0 2 391 459 425 48.1 2 33S 546 440 149.2 2 .2 .3 .2 .07 2 .1 .2 .2 .07 2 .1 .4 .2 .21 2 Atill4AL NUMBER ----- Group: 1 I05S29 105549 MEAII S.D. N Group: 3 105539 IUSS52 HEAII S.D. N Group: 4 IOSS33 IOSS42 MEAN S.D. N APPENDIX 4 individual Clinical Hematology Data Females Day 245 WBC XIO /itL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOXIC ACID POTASSIUM SALT (PPOS: T-6295) III CY110ttOLGUS ii-SEC LYMPH XIO'/)jL X10'/j4L -------- -------- M0140 EOSIN KIO'/i,L X10@ls4L -------- -------- BASO H-SEG% X10"/ijL -------- -------- LYMPH% -------- MONO% -------- EOSI ----- ]Dose Level: 0 12.5 9.1 10.3 5.1 11.4 1.56 2 7.1 2.83 2 Dose Level: 0.15 7.5 .9 11.4 5.1 9.4 2.76 2 3.0 2.97 2 I)OSO Level: 0.75 10.8 4.5 11.1 2.6 11.0 .22 2 3.6 1.34 2 Dosage Unit: nig,kgiday 2.8 .5 .1 4.1) .9 .3 3.4 .7 .2 a,; .28 .14 2 2 2 Doza@ia Unit: nig!kcj/day 5.3 1.0 .2 4.6 1.0 .6 5.0 1.0 .4 .49 .00 .28 2 2 2 Dosage Unit: mg/kg/day 5.0 1.1 .2 7.S .7 .3 6.2 1.77 2 .9 .2 .28 .07 2 2 .0 .0 .0 or) 2 .1 .0 .0 .07 2 1 .1 .1 .00 2 73 50 62 16.3 2 12 45 28 23.3 2 41 23 32 12.7 2 22 39 30 12.0 2 71 40 S6 21.9 2 46 67 S6 14.9 2 4 8 6 2.8 2 13 9 11 2.8 2 10 6 a 2.8 2 APPENDIX 4 individual clinical Hematology Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUORGOCTANE SULPONIC ACID POTASSIUM SALT (PPOS; T-62951 IN CYNOMOLGUS A141RAL NUFIBER ------ Aillso -------- POLY -------- POIK -------- HYPO -------- TO)UIEUT -------- Group:, I 105529 105549 a Group: 3 105539 105552 Group: 4 IOS533 105542 Dose Level: 0 - Dose Level: 0.15 - Dose Level: 0.75 - Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day. Dosage Unit: mg/kg/day a Plasmodium was observed. ANIKAL NMBER Group: 1 105520 105526 HEA14 S.D. N Group- 3 105505 IOSS23 MEAN S.D. N Gro,up: 4 105511 105522 KEAN S.D. N APPENDIX 4 individual Clinical Hematolc)jy Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT IPFOS; T-6295) IN CYNOMOIGUS RBC HGB HCT mcv TICH MCHC PLT RETIC RET X107/1#L t xio X10, /isL C/DL % FL PG -------- -------- -------- - ------ -------- -------- -------- -------- ----- Dose Level: 0 6.78 6.67 12.9 12.4 6.72 .079 2 12.6 .35 2' Dose Level: 0.15 6.89 6.71 13.6 12.6 6.80 .127 2 13.2 .57 2 Dose Level: 0.7S 6.08 6.36 11.5 12.1 6.22 .198 2 11.8 .42 2 Dosage unit: mgikglday 40.6 39.8 40.2 s7 2 S9.8 S9.7 59.8 .07 2 19.0 19.6 18.8 .28 2 Dosage Unit: mg/kg/day 43.2 40.6 62.6 60.5 19.8 19.1 41.9 1.84 2 61.5 1.48 2 19.4 .49 2 Dosage Unit: mg/kg/day 37.8 38.3 38.1 .35 2 62.1 60.2 61.1 1.34 2 18.9 19.0 19.0 .07 2 31.8 31.2 31.S .42 2 31.6 31.5 31.S .07 2 30.5 31.5 31.0 .71 2 692 396 S44 209.3 2 434 548 491 80.6 2 542 603 572 43.1 2 .5 .1 .3 .28 2 .2 .1 .2 o7 2 .8 .3 .6 .35 2 APPENDIX 4 3 ANIMAL NUMBER - -- - - - Group: IOSS2U 105526 MEAN S.D. N Group- 3 iossos IOSS23 HEM S.D. N croup: 4 iossil 105522 MEAN S.D. N individual Clinical Hematology Data Males Day 322 WBC Xio@/jiL - -- - - - - - 26-WEEK CAPSULE TOXICITY SMY WITH PERFLUOROOCTANE SULFONIC ACID poTASSIUM SALT TPFOS; T-6295) IN CYNOMOLGUS N-SEG X10'/ijL - -- -- - -- LYMPH XIO'li4L - -- - -- -- J40140 X10'/itL -- - - --- - EOSIII BASO X10.'lo4L X10'/itL - -- - -- - - - - -- - - - N-SEG% - -- - -- - - LYFIPH% -- -- -- - - motio% 7 - -- - -- - EOSIN - -- - -- Dose Level: 0 9.S 4.3 7.8 4.0 8.6 1.20 2 4.2 .21 2 Dose Level: 0.15 13.7 9.6 11.8 6.7 12.9 1.34 2 9.2 2.OS 2 Dose Level: 0.75 6.3 2.2 11.6 5.8 9.0 3.7S 2 4.0 2.SS 2 Dosage Unit: nio/ko/day 4.5 .6 .1 3.0 .7 .1 3.8 1.06 2 .6 .1 .07 .00 2 2 Dosage unit: mg/kg/day . 3.0 .9 2 4.4 .6 .1 3.7 .8 .2 .99 .21 o7 2 2 2 Dosage Unit: mg/kg/day 3.1 .8 .2 4.7 .9 .1 3.9 1.13 2 .8 .2 .07 .07 2 2 .0 .0 .0 .00 2 .0 .0 .0 .00 2 .1 .0 .0 .07 2 45 52 48 4.9 2 70 57 64 9.2 2 36 50 43 9.9 2 47 38 42 6.4 2 22 37 30 10.6 2 49 40 44 6.4 2 7 9 a 1.4 2 7 5 6 1.4 2 12 a 10 2.8 2 APPENDIX 4 Individual clinical Hematology Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAIIE SULPONIC POTASSIUM SALT (PFOS: T-629S) IN CYNO14OLGUS ACID ANIMAL 14UMBER ------ Atilso -------- POLY -------- POIX -------- HYPO -------- TOXNEUT -------- Group; 1 105520 105526 Croup: 3 105505 iOSS23 Group: 4 105511 105S22 Dose Level: 0 - Dose Level: 0.15 - Dose Level: 0.75 - Dosage Unit: mg/kglday Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day ANIMAL NUMBER Group-. 1 105529 105549 MEAli S.D. 1] Group: 3 IOSS39 IOSS52 KEAN S.D. N Group: 4 105533 105542 MEM S.D-. APPENDIX 4 Individual Clinical Hematology Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOIIIC ACID POTASSIUM SALT IPFOS; T-6295) IN CYNOMOLGUS RBC XIO*/ijL -------- HGE G/DL -------- HCT -------- mcv FL -------- MCH PG -------- MCHC -------- X10PL-.T/i#L -------- RETIC % -------- RLrr xio ----- Dose Level: 0 Dosage Unit: niglkg/day 6.04 11.9 36.9 61.1 19.7 32.2 645 .1 6.61 12.8 39.9 60.4 19.4 32.1 447 .3 6.32 12.3 38.4 60.8 19.6 32.1 546 .2 .403 .64 2.12 .49 .21 .07 140.0 .14 2 2 2 2 2 2 2 2 Dose Level: O.lS Dosage Unit: mg/kg/day 6.81 12.S 39.6 SB.2 19.3 31.5 399 .4 6.71 12.S 40.7 60.7 18.6 30.6 S46 .3 6.76 12.S 40.1 S9.4 19.4 31.0 472 .4 .071 .00 .79 1.77 .21 .64 103.9 .07 2 2 2 2 2 2 2 2 Dose Level: 0.7S Dosage Unit: mg/ka/day 6.20 11.6 37.9 61.2 18.8 30.7 314 .1 6.81 12.2 41.0 60.3 17.9 29.7 534 .5 6.50 11.9 39.5 60.8 18.4 30.2 424 .3 .431 .42 2.19 .64 .64 .71 155.6 .28 2 2 2 2 2 2 2 2 ANIMAL NUMBER Group: I 105S29 1(15549 MEAN S.D. N Group: 3 105539 105552 MEAN S.D. N Group: 4 105533 105542 HEM S.D. N APPENDIX 4 Individual clinical Hematology Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAIIE SULPONIC ACID POTASSIUM SALT (PPOS; T-629S) IN CYIIOMOLGUS WBC XIO'/i,L N-SEG Xlo,/;iL -------- LYMPH X10'/I,L -------- 140140 X10 lj4L -------- EOSIII X10"/i4L -------- BASO Xlol/i#L -------- N-SEG% -------- LYMPH% -------- MONO% -------- EOSI ----- Dose Level: 0 Dosage Unit: nig/kg/day 14.9 10.0 3.2 1.4 .2 .0 67 22 10 8.7 4.4 3.3 .6 .3 .0 51 38 7 11.8 7.2 3.2 1.0 .2 .0 59 30 8 4.38 3.96 .07 .57 .07 .00 11.3 11.3 2.1 2 2 2 2 2 2 2 2 2 Dose Level: 0.15 Dosage unit: mg/kg/day 7.4 2.0 4.S .7 .2 .0 27 61 10 11.4 6.5 3.9 .4 .6 .0 57 34 4 9.4 4.2 4.2 .6 .4 .0 42 48 7 2.83 3.18 .42 .21 .28 .00 21.2 19.1 4.2 2 2 2 2 2 2 2 2 2 Dose Level: 0.75 Dosage Unit: mg/kg/day 7.8 2.3 5.0 .5 .1 .0 29 63 7 10.0 3.1 6.1 .6 .2 .0 31 61 6 8.9 2.7 5.6 .6 .2 .0 30 62 6 1.56 .57 .78 .07 .07 .00 1.4 1.4 .7 2 2 2 2 2 2 2 2 2 APPENDIX 4 individual clinical Hematology Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOUIC ACID POTASSIUM SALT IPFOS; T-6295) IN CYNOMOLGUS ANIMAL TIUMBER ------ ANISO -------- POLY -------- POIK -------- HYPO -------- TOXNEUT -------- Group: 1 1(15529 105549 Group: 3 105539 IOSSS2 Group: 4 105533 106542 Dose Level: 0 - Dose Level: O.lS - Dose Level: 0.7S - Dosage unit: mgikg/day Dosage Unit: mg/kg/day Dosage Unit: mg/kglday ANIMAL NUMBER ------ Group: 1 105520 IOSS26 HEM S.D. N Group: 3 iossos 105523 MEAN S.DN Group: 4 105511 105522 MEAN S.D. N APPENDIX 4 individual Clinical Hematology Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS: T-6295) IN CYIIO140LGUS RBC XIO'/)iL -------- HGB G/DL -------- HCT % -------- mcv FL -------- MCN PG -------- MCHC % -------- P@@T X10 /siL -------- lrzrlc t -------- RETI xlo,/ ------ Dose Level: 0 6.82 6.44 13.3 12.5 6.63 .269 2 12.9 .57 2 Dose Level: 0.15 7.19 7.12 14.1 13.8 7.16 .049 2 14.0 .21 2 Dose Level: 0.75 5.93 6.68 11.9 13.2 6.30 .530 2 12.6 .92 2 Dosage Unit: mg/kglday 41.2 39.3 60.4 61.0 19.4 19.4 40.2 1.34 2 60.7 .42 2 19.4 .00 2 Dosage Unit: mgtkg/day 46.3 44.9 64.3 63.0 19.6 19.4 45.6 .99 2 63.7 .92 2 19.5 .14 2 Dosage Unit: mo/kg/day 38.7 42.5 65.3 63.7 20.1 19.8 40.6 2.69 2 64.5 1.13 2 19.9 .21 2 32.2 31.8 32.0 .28 2 30.5 30.8 30.6 .21 2 30.9 31.1 31.0 .14 2 584 337 460 174.7 2 415 566 490 106.8 2 445 576 sio 92.6 2 .4 .2 .3 .14 2 .5 .1 .3 .28 2 1.4 .0 .7 .99 2 ANIMAL NUMBER ------ Group: 1 iOSS20 IOSS26 HEAII S.D. N Group: 3 itissos IOSS23 MEAN S.D. N Group: 4 105511 iD5S22 MEAN S.D. N APPENDIX 4 individual Clinical Hematology Data males Day 456 WBC X10'/IiL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PEP.FLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLCUS ACID N-SEG LYMPH X10,114L XIO'loiL -------- -------- 140110 EOSIII X.10,/itL X101/jiL -------- -------- BASO N-SEG% XIO /tiL -------- ------ - LYitPH% 140NO% -------- - ------ EOSI ----- Dose Level: 0 11.2 12.Q 11.6 .57 2 5.4 7.5 6.4 1.48 2 I)ose Level: 0.15 10.7 4.1 12.5 S.7 11.6 1.27 2 4.9 1.13 2 Dose Level: 0.7S 12.0 21.2 7.5 13.1 16.6 6.Sl 2 10.3 3.96 2 Dosage Unit: mg/kg/day 4.9 .7 .1 3.8 .6 .1 4.4 .6 .1 .78 .07 .00 2 2 2 Dosage Unit: mg/ka/day 5.6 .8 .2 .6.2 s .2 5.9 .6 .2 .42 .21 .00 2 2 2 Dosage Unit: mg/kg/day 3.5 .7 .2 6.0 1.6 .5 4.8 1.2 .4 1.77 .64 .21 2 2 2 .1 .0 .0 .07 2 .0 .0 .0 .00 2 .1 .1 .1 .00 2 48 62 ss 9.9 2 38 45 42 4.9 2 63 62 62 .7 2 44 32 38 8.5 2 52 49 so 2.1 2 29 28 28 .7 2 6 5 6 .7 2 7 4 6 2.1 2 6 7 6 .7 2 APPENDIX 4 individual Clinical Hematology Data males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUN SALT (PFOS: T-6295) IN CYNOMOLCUS ANIMAL NUMBER ------ ANISO POLY POIX HYPO TOXNEUT ---- --- ---------------- ---------------- Group: 1 IOSS20 105526 Group: 3 105505 105523 Group: 4 Dose Level: 0 - Dose Level: 0.15 - Dose Level: 0.75 Dosage Unit: mg/kg!day Dosage Unit: mg/kgiday Dosage unit: mg/kg/day 105511 105522 ANIMAL NumiaER ------ Groi.ip- I IOSS29 IOSS49 mmi S.D. la Group: 3 105539 105552 MEAN S.D. N Group: 4 105533 105542 MEAN S.D. APPENDIX 4 individual CliniCal Hematology Data Females Day 4S6 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS P.BC X10* /j4L -------- HGB G/DL -------- . HCT % -------- mcv FL -------- MCH PG -------- tfchc % -------- PLT X10'/i4L -------- P.ETIC It -------- RET xio ----- Dose Level: 0 Dosage Unit: mg/kglday S.63 11.3 3d.8 61.8 20.1 32.6 S80 .6 6.88 13.5 42.2 61.3 19.6 31.9 407 .4 6.26 12.4 38.S 61.6 19.8 32.2 494 .5 .884 1.56 5.23 .35 .35 .49 122.3 .14 2 2 2 2 2 2 2 2 Dose Level: 0.15 Donage Unit: mcj/kg/day 6.61 12.7 40.2 60.9 19.3 31.7 441 .4 6.70 12.7 41.4 61.9 19.0 30.6 461 .2 6.66 12.7 4(1.8 61.4 19.2 31.2 451 .3 .064 .00 .8s .71 .21 .78 14.1 .14 2 2 2 2 2 2 2 2 Dose Level: 0.75 Dosag* Unit: mg/kg/day 6.62 12.7 40.7 61.4 19.1 31.2 293 .0 7.51 13.5 45.2 60.1 18.0 29.9 598 .3 7.06 13.1 42.9 60.8 18.5 30.6 446 .2 .629 .57 3.18 .92 .78 .92 215.7 .21 2 2 2 2 2 2 2 2 ANIMAL NUMBER Group: I IOSS29 105549 HEAII S.D. N Group - 3 IOSS39 IOSS52 mmi S.D. N Group: 4 105533 IOSS42 MEAN S.D. N APPENDIX 4 individual Clinical Hematology Data Females Day 4S6 W PC XIO /piL 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS: T-629S) IN CYNOMOLGUS N-SEIG LYMPH Xio /liL X10'/itL --------- -------- 140110 XIO'lAtL -------- EOSIII X10'/jiL ------- BASO H-SEG% LYMPH% XIO'/i,L -------- -------- -------- NOIIO% -------- ROSIN ------ Doze Level: 0 8.2 4.5 9.3 4.3 8.8 .78 2 4.4 .14 2 Dose Level: 0. 15 11.1 5.0 8.7 2.6 9.9' 1.70 2 3.8 1.70 2 Dose Level: 0.7S 9.9 3.5 11.2 2.5 10.6 .92 2 3.0 .71 2 Dosage Unit: mg/kg/day 2.9 .6 .2 3.8 .8 .4 3.4 .7 .3 .64 .14 .14 2 2 2 Dosage unit: mg/kg/day 4.7 1.0 .4 4.6 .8 .8 4.6 .9 .6 .07 .14 .28 2 2 2 Dosage Unit: mg/kg/day 5.1 1.0 .2 7.3 .9 .4 6.2 1.0 .3 l.s6 .07 .14 2 2 2 .0 .0 .0 .00 2 .0 .0 .0 .00 2 .1 .2 .2 .07 2 55 46 50 6.4 2 45 29 37 11.3 2 36 22 29 9.9 2 36 41 38 3.5 2 43 S2 48 6.4 2 si 65 se 9.9 2 7 8 7 2 9 9 9 .0 2 10 8 9 1.4 2 3 APPENDIX 4 individual Clinical Hematology Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-629S) IN CY140140tdGUS AlilMAL IIU@IBER ------ ANISO -------- POLY -------- POIK -------- HYPO -------- TO]OIEUT -------- Group: I Dose Level: 0 Dosage Unit: mg4kg/day IOS529 iOSS49 Group: 3 - Dose Level: 0.15 Dosaoe Unit: mg/ka.;day ZOSS39 - 105552 - Group. 4 Dose Level: 0.75 Dosage Unit: mg/kg/day IOSS33 - 105542 - ANIMAL NUKBER ------ Group: 1 IOSS20 IOSS26 MEAN S.D. N Group: 3 IOS505 105523 MEAN S.D. n Group: 4 105511 IOSS22 MEAN s.D. N APPENDIX 4 Individual clinical Hematology Data Males Day S46 26-wEzK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS: T-629S) IN CYNOMOLCUS RBC X10'/IL -------- HGB G/DL -------- HCT t -------- mcv FL -------- MCH PG -------- MCHC % -------- PLT Rjrric X10'/itL t -------- -------- RET7 xio, ------ Dose Level: 0 Dosage Unit: mg/kg/day 6.S4 12.6 39.9 61.0 19.2 31.5 503 .7 6.s9 12.6 41.4 62.8 19.1 30.5 366 .3 6.S6 12.6 40.7 61.9 19.2 31.0 434 .5 .035 u(i 1.06 1.27 .07 .71 96.9 .28 2 2 2 2 2 2 2 2 Dose Level: 0.15 Dosage Unit: mg/kg/day 6.80 13.5 43.6 64.1 19.8 30.9 377 .7 7.00 13.8 44.2 63.1 19.8 31-3 369 .7 6.90 13.6 43.9 63.6 19.8 31.1 373 .7 .141 .21 .42 .71 .00 .28 S.7 .00 2 2 2 2 2 2 2 2 Dose Level: 0.75 Dosage Unit: mg/kg/day 6.42 12.7 43.5 67.6 19.7 29.2 478 .9 6.42 12.5 41.3 64.3 19.5 30.3 562 .3 6.42 12.6 42.4 66.0 19.6 29.8 520 .6 .000 .14 1.56 2.33 .14 .78 59.4 .42 2 2 2 2 2 2 2 2 ANIMAL NUMBER Group: 1 105520 105526 HEM S.D. N Group: 3 105SO5 105523 MEAN S.D. N Group: 4 iossii 105522 MEAN S.D. N APPENDIX 4 individual clinical Hematology Data males Day 546 WBC XIOI/piL 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-62951 IN CYNONOLGUS N-SEG X10'/iiL -------- LYMPH XIO'/;iL -------- Nolio ilO'lAiL -------- EOSI14 X10'/iiL -------- EKASO X10'/itL -------- N-SEG% -------- LY@IPH% -------- MONO% -------- EOSIN ------ Dose Level: 0 7.1 2.0 9.6 4.2 8.4 1.77 2 3.1 l.s6 2 Dose Level: 0.15 8.1 13.7 6.2 10.9 3.96 2 5.0 1.70 2 t)ose Level: 0.75 15.7 16.2 10.9 8.8 16.0 .3S 2 9.8 1.48 2 Dosage Unit: mg/kglday 4.3 .5 .1 4.1 1.1 .1 4.2 .8 .1 .14 .42 .00 2 2 2 Dosage Unit; nV/kg/day 3.2 .9 .2 6.2 .7 .5 4.7 .8 .4 2.12 14 .21 2 2 2 Dosage Unit: mglkg/day 3.4 1.2 .1 5.4 1.3 .4 4.4 1.2 .2 1.41 .07 .21 2 2 2 .3 .0 .2 .21 2 .1 .1 .1 .00 2 .1 .3 .2 .14 2 28 44 36 11.3 2 47 45 46 1.4 2 ?Q 54 62 11.3 2 60 43 52 12.0 2 39 415 42 4.2 2 22 33 28 7.8 2 7 11 9 2.8 2 11 5 a 4.2 2 7 .7 2 APPENDIX 4 individual clinical Hematology Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT IPFOS; T-6295) IN CYTIOMOLCUS ACID ANIMAL NUMBER ------ pliso -------- POLY -------- POIK -------- HYPO -------- TOXNEUT -------- Group: 1 Dose Level: 0 Dosage Unit: mg!kg/day 105520 IOSS26 Group: 3 - Dose Level: 0.15 Dosage Unit: mg/kg/day I0550S - 105523 - Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day 105511 - IOS522 - ANIMAL NUMBER Group: 1 IOSS29 IOSS49 MEAN S.DN Group. 3 ZOSS39 IOSSS2 MEAN S.D. N Group: 4 105533 105S42 HEAJN s.DN APPENDIX 4 individual clinical Hematology Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTPIIE SULFOIIIC ACID POTASSIUM SALT IPFOS; T-6295) IN CYIIOMDLGUS RBC XIO'/itL -------- HGB G/DL -------- HCT t -------- HCV FL -------- MCH PG -------- MCHC % -------- PLT P.ETIC X10'/)iL % -------- -------- RETX xio' ------ Dose Level: 0 Dosage Unit: mg/kg/day 5.S2 11.1 34.6 62.6 20.1 32.1 S33 .6 6.51 12.6 40.5 62.3 19.4 31.1 483 .3 6.02 11.8 37.5 62.5 19.8 31.6 SOS .4 .700 1.06 4.17 .21 .49 .71 35.4 .21 2 2 2 2 2 2 2 2 Dose Level: O.IS Dosage Unit: mg/kg/day 6.60 12.6 41.2 62.4 19.1 30.7 405 .3 6.33 12.0 39.3 62.1 18.9 .30.5 408 .6 6.46 12.3 40.2 62.2 19.0 30.6 406 .4 .191 .42 1.34 .21 .14 .14 2.1 .21 2 2 2 2 2 2 2 2 Dose Level: 0.75 Dosage Unit: mo/ka/day 6.62 12.5 41.0 61.9 18.9 30.5 293 .2 6.81 12.3 40.6 59.7 18.1 30.3 500 .4 6.72 12.4 40.8 60.8 ie.s 30.4 396 .3 .134 .14 .28 2.S6 .57 .14 146.4 .14 2 2 2 2 2 2 2 2 A141MAL NUMBER ------ Group: I itiSS29 iOSS49 MEAN S.D. 11 Group: 3 105539 105552 MEAN S.D. N Group: 4 105533 ZOSS42 MEAN S.D. N APPENDIX 4 individual Clinical Hematology Data Females Day 546 WBC X10'/;jL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PEPFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS: T-629S) IN CYNOMOLCUS li-SEG Xio@/A#L -------- LYMPH XIOI/jiL -------- MONO EOSIII i(10'lsiL XIO@/ijL -------- -------- BASO X10'/jjL ----- -- N-SEG% LYt4PH% 140110% EOSIT -------- -------- -------- ------ Dose Level: 0 Dosage Unit: mg/kgiday 6.9 3.5 2.5 .7 .2 .1 so 36 10 15.6 10.5 3.2 1.3 .4 .2 67 20 9 11.2 7.0 2.8 1.0 .3 .2 58 28 io 6.15 4.95 .49 .42 14 o7 12.0 11.3 .7 2 2 2 2 2 2 2 2 2 Dose Level: 0.15 Dosage Unit: mg/kglday 13.8 7.1 5.1 1.0 .4 51 37 8 9.2 3.8 3.4 1.1 .7 .2 41 37 12 11.5 5.4 4.2 1.0 .6 .2 46 37 10 3.25 2.33 1.20 .07 .21 .00 7.1 .0 2.8 2 2 2 2 2 2 2 2 2 Dose Level: 0.75 Dosage unit: mg/kglday 9.8 3.2 5.7 S .1 .2 33 58 s 11.0 3.0 7.0 .5 .3 .1 28 64 5 10.4 3.1 6.4 .5 .2 .2 30 61 s .07 3.5 4.2 .0 .85 .14 .92 .00 .14 2 2 2 2 2 2 2 2 2 APPENDIX 4 individual clinical Hematology Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT IPFOS; T-6295) IN CYNOMOLGUS ANI14AL NUMBER ------ AIIISO POLY POIK HYPO TOXNEUT -------- -- ----- -------- -------- -------- Group: I IOSS29 I05S49 Group: 3 105539 iOS552@ Group: 4 105533 105542 Dose Level: 0 - Dose Level: D.lS - Dose Level: 0.75 - Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Dosage unit: mg/kg/day ANIMAL NUMBER ------ Groupt I 105508 105517 105519 105520 105526 105527 HRM S.D. N Group: 2 IOSS14 1055is 105516 105521 MEAN S.D. N Group-. 3 lossos 105510 iossis 105523 105524 105528 HEM S.D. Appendix 4 individual Clinical Chemistry Data Males Day -27 26-WEM CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS OLU UN CREAT T PRO ALD GLOB G/DL T BILI MG/DL SBA UMOL/L CHOL NO/DL NO/DL -------- MG/DL -------- MG/DL -------- G/DL -------- G/DL -------- -------- -------- -------- -------- Done Levels 0 62 22 76 21 74 27 69 17 75 19 99 17 76 12.5 6 20 3.8 6 Doze Level: 0.03 76 17 69 17 se 29 75 16 70 8.3 4 20 6.2 4 Dose Level: 0.15 59 20 138 16 95 22 76 20 69 25 se 24 82 30.4 6 21 3.3 6 Dosage Unitt mg/kg/day 1.0 8.7 4.6 1.3 9.2 4.7 1.2 9.3 5.0 1.1 8.7 4.9 1.1 9.4 5.2 1.2 8.8 4.9 1.2 .10 6 9.0 .32 6 4.9 .21 6 Dosage unit: mg/kg/day 1.2 1.0 1.1 1.4 1.2 .17 4 9.7 9.5 8.8 10.2 9.6 .58 4 S.5 4.6 S.0 5.6 5.2 .46 4 Dosage Unit: mg/kg/day 1.2 9.3 5.2 .9 8.8 4.4 1.5 10.1 5.3 1.1 9.3 5.2 1.4 9.6 5.2 1.3 9.7 5.2 1.2 .22 6 9.5 .44 6 S.1 .34 6 4.1 4.5 4.3 3.8 4.2 3.9 4.1 .26 6 4.2 4.9 3.8 4.6 4.4 .48 4 4.1 4.4 4.8 4.1 4.4 4.5 4.4 .26 6 1.3 1.0 .3 .7 .3 .2 .6 .45 6 .5 .2 .6 .3 .4 .18 4 1.3 .3 .5 .3 .7 .7 .6 .37 6 5 11 10 9 9 9 9 2.0 6 es 137 174 ill iso 170 138 33.7 6 9 8 11 8 9 1.4 4 138 ill 98 93 110 20.1 4 14 10 9 8 10 a 10 2.2 6 186 157 124 224 141 175 151 26.1 6 565 ANIMAL NUMBER ------ Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 Individual Clinical Chemistry Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS GLU MG/DL -------- UN MG/DL -------- CREA@ MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SRA UNOL/L -------- CHOL MG/DL -------- Dose Level: 0.75 67 18 102 22 71 22 58 21 75 22 64 le 73 15.4 6 20 2.0 6 Dosage Uniti mg/kg/day 1.3 9.6 5.1 1.4 9.9 5.0 1.4 9.5 5.3 1.1 8.8 4.7 1.3 9.2 5.3 1.3 9.5 5.5 1.3 .11 6 9.4 .38 6 5.2 .28 6 4.5 4.9 4.2 4.1 3.9 4.0 4.3 .37 6 .4 .4 .8 1.0 .3 .3 .5 .29 6 10 7 10 8 10 9 9 1.3 6 129 121 117 115 lee 159 138 29. 6 566 ANIMAL NUMBER ------ Group: 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 iossis 105516 105521 MEAN S.D. N Group: 3 105510 105518 105523 105524 105528 MEAN S.D. N Appendix 4 Individual Clinical Chemistry Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID AST/SGOT ALT/SGPT ALK PHOS GGT SDH CK AXYLASE LIPASE p --I-U-/-L--- --I-U-/-L--- --I-U-/-L--- --I-U-/-L--- --I-U-/-L--- ---IU-/-L--- ---IU-/-L--- ---IU-/-L--- U/ Dose, Level: 0 58 84 58 36 58 43 56 16.5 6 24 51 33 26 31 29 32 9.7 6 Dosage Unit: mg/kg/day 546 152 8 628 125 9 514 117 9 866 Be 4 1156 211 7 556 113 6 711 134 7 252.6 42.8 1.9 6 6 6 1086 1908 783 660 1671 692 1133 535.3 6 451 508 448 336 250 376 39S 93.4 6 12 226 12 17 25 37 55 84.4 6 Dose Level: 0.03 53 27 38 43 43 48 43 26 44 6.3 4 36 11.2 4 Dosage Units mg/kg/day 642 155 4 787 125 4 1002 182 2 369 103 3 700 141 3 265.6 34.5 1.0 4 4 4 1955 348 848 595 936 709.0 4 413 715 435 340 476 164.6 4 19 43 60 17 35 20.6 4 Dose Level: 0.15 66 99 39 29 54 34 99 78 84 118 93 56 72 23.5 6 69 35.7 6 Dosage Unit: mg/kg/day 720 194 12 814 130 4 579 124 2 716 82 16 1165 154 10 624 278 5 770 160 8 210.3 68.4 5.4 6 6 6 670 1109 1047 1549 820 1329 1087 322.3 6 367 450 326 471 469 236 396 94.5 6 133 15 33 29 56 39 51 42.4 6 567 ANIMAL NUMBER ------ Group: 4 iOS506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE 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 -------- ANYLASE IU/L -------- LIPASE ZU/L ------- p U/ ---- Dose Level: 0.75 54 49 54 94 80 181 71 32 69 48 80 78 68 11.7 6 so 54.2 6 Dosage Unit: mg/kg/day 1443 167 447 138 585 156 927 199 646 105 992 259 840 360.9 6 171 53.3 6 6 9 6 6 5 5 6 1.5 6 1602 575 1265 540 907 1676 1094 497.4 6 653 515 704 543 396 362 529 135.6 6 52 19 39 99 15 21 41 31.8 6 568 Appendix 4 Individual Clinical- Chemistry Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOST T-6295) IN CYNOMOLGUS SULFOUIC MONKEYS ACID ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 105508 105517 105519 105520 105526 105527 mm S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 MEAN S.D. N Dose Level: 0 10.2 6.5 10.3 5.8 11.1 6.6 10.5 6.1 11.8 7.5 10.7 5.0 10.0 .60 6 6.2 .84 6 Dose Level: 0.03 12.2 6.5 11.3 6.9 11.1 7.1 12.0 6.1 11.6 .53 4 6.6 .44 4 Dose Level: 0.15 11.9 5.9 10.7 7.5 12.2 6.9 11.2 6.6 11.9 8.8 10.9 6.7 11.5 .62 6 7.1 .99 6 Dosage Unit: mg/kg/day 154 4.9 106 154 4.8 106 161 5.9 113 ise 5.7 ill 166 6.1 ill 160 4.9 109 159 4.6 6 5.4 .59 6 109 2.9 6 Dosage unit: mg/kg/daY 171 6.2 114 159 5.8 110 159 5.5 109 167 6.1 112 164 6.0 4 5.9 .32 4 ill 2.2 4 Dosage unit: mg/kg/day 161 5.8 112 156 5.8 ill 169 7.2 113 164 6.1 116 168 7.0 110 158 6.3 108 163 5.3 6 6.4 .60 6 112 2.7 6 569 Appendix 4 individual Clinical Chemistry Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID ANIMAL' NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 4 105506 105507 iOS509 105511 105512 105522 MEAN S.D. N Dose Level: 0.75 11.8 8.0 11.3 6.0 10.9 5.9 10.5 6.1 11.8 7.0 11.7 8.3 11.3 .54 6 6.9 1.06 6 Dosage unit: mg/kg/daY 165 6.1 112 157 6.5 108 158 5.5 104 156 4.8 106 162 5.8 109 168 6.3 110 161 4.8 6 5.8 .62 6 108 2.9 6 570 ANIMAL NUMBER ------ Group: I 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID GLU MG/DL -------- UN MG/DL -------- CREAI MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA UNOL/L -------- CHOL MG/DL -------- Dose Level: 0 54 23 108 23 70 23 51 19 82 22 92 21 76 22.2 6 22 1.6 6 Doge Level: 0.03 71 21 66 23 89 22 67 24 Dosage Unit: mg/kg/day 1.2 9.4 5.1 1.3 9.9 5.5 1.3 8.6 4.6 1.3 9.9 4.6 1.2 10.8 4.7 1.1 9.0 4.9 1.2 .08 6 9.6 .78 6 4.9 .35 6 Dosage Unit: mg/kg/day 1.3 10.0 4.9 1.2 9.2 4.5 1.2 8.9 4.6 1.1 9.0 4.8 4.3 4.4 4.0 5.3 6.1 4.1 4.7 .83 6 5.1 4.7 4.3 4.2 1.2 .3 .5 .5 .4 .3 .5 .34 6' .5 .7 .3 .6 7 10 7 4 7 7 7 1.9 6 5 6 9 6 93 168 137 203 133 159 149 37. 6 120 133 146 120 73 22 1.2 9.3 4.7 4.6 .5 10.7 1.3 .08 .50 .18 .41 .17 4 4 4 4 4 4 4 6 130 1.7 12. 4 4 DoSe Level: 0.15 Dosage Unit% mg/kg/day 86 20 1.2 10.7 5.5 5.2 .8 7 162 87 21 1.1 9.8 5.2 4.6 .3 7 142 02 29 1.3 9.2 3.9 5.3 .6 7 141 72 20 1.1 9.1 4.7 4.4 .9 37 156 55 21 1.0 9.1 4.4 4.7 .5 11 122 74 27 1.1 9.8 4.6 5.2 .6 6 140 76 23 1.1 9.6 4.7 4.9 .6 12 144 12.0 3.9 .10 .62 .57 .38 .21 12.1 14 6 6 6 6 6 6 6 6 6 571 ANIMAL NUMBER ------ Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 Individual Clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; 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: 0.75 106 27 71 21 88 17 74 26 71 75 60 26 78 16.3 6 24 3.9 6 Dosage Unit: mg/kg/day 1.3 9.4 4.9 1.4 10.1 5.5 1.2 10.5 4.6 1.1 8.6 4.4 1.3 8.9 4.6 .9 8.8 4.5 1.2 .10 6 9.4 .78 6 4.8 .40 6 4.5 4.6 5.9 4.2 4.2 4.3 4.6 .65 6 .4 .4 .3 .4 .5 1.3 .6 .37 6 11 163 8 149 9 137 8 164 9 152 7 158 9 154 1.4 10 6 6 572 ANIMAL NUMBER ------ Group: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group.- 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT IPFOS: T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID AST/SGOT ALT/SGPT IU/L IU/L -------- -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- NffLASE IU/L -------- LIPASE IU/L -------- p u --- Dose Level: 0 66 202 65 211 75 215 61 48 61 82 55 83 64 6.7 6 140 76.9 6 Dose Levelt 0.03 68 89 54 146 44 so 50 98 54 10.2 4 103 29.4 4 Dose Level: 0.15 77 76 68 135 39 65 140 160 74 143 48 78 74 35.5 6 110 41.0 6 Dosage Unit: mg/kg/day 195 101 3 274 121 5 217 98 7 550 163 5 256 204 3 254 50 3 291 123 4 130.1 54.0 1.6 6 6 6 Dosage Uniti mg/kg/day 200 166 2 184 72 3 210 62 3 211 75 4 201 12.5 4 94 48.5 4 3 .8 4 Dosage Unit: mg/kg/day 201 127 2 454 120 4 122 64 2 199 41 8 334 go 6 232 91 3 257 87 4 118.5 32.9 2.4 6 6 6 484 1568 792 872 896 1242 979 384.3 6 706 395 477 356 484 156.7 4 1192 1003 362 663 1073 769 844 306.4 6 425 281 360 314 595 272 374 121.9 6 219 293 433 566 378 153.7 4 366 411 269 484 352 617 416 121.0 6 27 39 46 12 27 19 28 12.5 6 25 12 .17 48 26 15.9 A 35 46 44 25 0 62 35 21.2 6 573 ANI14AL NUMBER Group: 4 105533 105!534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (POOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGft ALK PHOS GGT SDH CK ANYLASS LIPASE p IU/L -------- IU/L -------- IU/L -------- IU/L -------- IU/L -------- IU/L -------- IU/L -------- IU/L -------- U/ ---- Dose Level: 0.75 101 216 63 ea 68 148 57 126 74 99 67 63 72 15.4 6 123 54.2 6 Dosage unit: mg/kg/day 301 121 5 329 64 3 575 63 7 182 52 4 204 79 3 269 70 1 310 75 4 141.4 24.3 2.0 6 6 6 3858 902 2229 417 1377 964 1624 1251.5 6 411 545 336 390 294 337 384 88.6 6 25 0 is 39 31 4 19 15.4 6 574 Appendix 4 individual Clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ANIMAL NUMBER ------ CA I PHOS NA x CL MG/D@ MG/DL MMOL/L MMOL/L MMOL/L -------- -------- -------- -------- -------- Group: I 105529 105530 105531 105535 105544 105549 Dose Level: 0 10.9 5.8 13.0 6.5 10.4 5.6 12.4 7.1 11.5 6.8 10.3 5.7 Dosage Unit- mg/kg/day 155 5.6 106 173 8.0 119 159 5.4 110 166 6.4 116 167 6.0 lie 156 5.7 112 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N 11.4 1.10 6 6.2 .63 6 Dose Level: 0.03 10.9 4.4 11.7 3.8 10.3 4.4 10.8 6.1 10.9 .58 4 4.7 .99 4 163 7.1 6 6.2 .96 6 114 5.0 6 Dosage unit: mg/kg/day 165 5.2 113 164 6.5 117 158 5.4 112 165 6.5 119 163 3.4 4 5.9 .70 4 115 3.3 4 Group: 3 105532 105538 105539 105545 10554e 105552 MEAN S.D. N t)ose Level: 0.15 11.5 6.2 11.5 5.6 10.5 6.1 10.3 4.9 10.6 5.3 11.6 7.1 11.0 .59 6 5.9 .78 6 Dosage Unit: mg/kg/day 167 6.4 113 164 6.3 116 164 6.3 lie 156 5.3 ill 152 5.5 112 166 7.0 lie 162 6.1 6 6.1 .63 6 115 3.1 6 575 Appendix 4 individual Clinical Chemistry Data Females Day -27 26-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 -------- x MMOL/L -------- CL MMOL/L -------- Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Dose Level: 0.75 10.9 5.1 11.6 5.7 12.1 5.7 10.7 6.1 11.7 4.7 10.7 5.6 11.3 .59 6 5.5 .50 6 Dosage Unit: mg/kg/day 163 5.1 lid 164 6.3 112 168 6.0 115 159 6.8 116 167 7.1 115 155 5.3 113 163 4.9 6 6.1 .80 6 114 1.5 6 576 ANIMAL NUMBER ------ Group: I 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 I0551i 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 MEAN S.D. N .Appendix 4 Individual Clinical Chemistry Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID GLU MG/DL -------- UN MG/DL -------- CREA@ T PRO MG/DL G/DL -------- -------- ALB GLOB G/DL G/DL -------- -------- T BILI MG/DL -------- SBA CHOL UMOL/L MG/DL -------- ---- Dose Level: 0 54 20 68 19 57 26 62 19 54 19 65 16 60 5.9 6 20 3.3 6 Dose Level: 0.03 65 22 72 14 58 21 53 16 62 8.3 4 is 3.9 4 Dose Level: 0.15 52 11 62 17 71 19 68 18 68 26 47 28 61 9.8 6 21 4.9 6 Dosage unit: mg/kg/day 1.1 9.2 4.8 1.2 9.9 4.8 1.1 8.5 4.5 1.0 8.7 4.8 .9 8.4 4.6 1.2 8.8 4.8 1.1 .12 6 8.9 .56 6 4.7 .13 6 Dosage Unit: mg/kg/day 1.4 10.0 5.7 1.1 9.9 4.8 1.0 7.8 4.7 1.3 9.5 4.9 1.2 .18 4 9.3 1.02 4 5.0 .46 4 Dosage Unit: mg/kg/day 1.1 9.0 5.0 .8 9.0 4.7 1.4 9.7 4.9 1.1 9.3 5.2 1.4 8.8 4.5 1.1 9.4 4.7 1.2 .23 6 9.2 .33 6 4.8 .25 6 4.4 5.1 4.0 3.9 3.8 4.0 4.2 .49 6 4.3 5.1 3.1 4.6 4.3 .85 4 4.0 4.3 4.8 4.1 4.3 4.7 4.4 .32 6 1.4 1.1 .4 .9 .4 .4 .9 .43 6 .6 .2 .4 .4 .4 .16 4 1.0 .3 .4 .3 .6 .7 .6 .27 6 8 11 9 7 10 8 9 1.5 6 lie 171 161 117 134 139 140 22 6 9 148 7 132 8 108 6 83 a lie 1.3 2 4 7 17 7 15 8 13 8 11 7 13 9 is a 14 .8 2 6 577 ANIMAL NUMBER ------ Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data males Day 37 GLU MG/DL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH pERpLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID UN MG/DL -------- CREAI MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA U14OL/L ----- -- CHOL MG/DL -------- Dose Level: 0.75 Dosage Unit: mg/kg/day 58 20 1.4 9.1 4.9 4.2 .5 75 24 1.4 9.4 5.0 4.4 .3 66 19 1.3 9.9 5.4 4.5 .4 54 21 1.1 9.3 4.5 4.8 .7 64 23 1.2 8.8 5.1 3.7 .2 71 le 1.3 9.4 5.5 3.9 .4 65 21 1.3 9.3 5.1 1.2 .4 7.8 2.3 .12 .37 .36 .40 .17 6 6 6 6 6 6 6 a 112 6 109 6 127 5 130 8 156 9 143 7 130 1.5 le. 6 6 578 ANIMAL NUMBER ------ Group: I 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN s D. N* Group: 3 105505 iossio 105518 105523 105524 105528 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS GGT SDH CK AMYLASE LIPASE IU/L -------- IU/L -------- IU/L -------- IU/L -------- IU/L -------- IU/L -------- IU/L -------- ZU/L -------- U/ ---- Dose Level: 0 37 53 46 26 35 71 45 15.9 6 30 59 28 23 27 69 39, 19.5 6 Dosage Unit: mg/kg/day 776 159 4 605 130 7 690 112 11 876 77 5 1552 203 9 830 126 7 888 134 7 339.5 42.9 2.6 6 6 6 173 170 231 99 160 1291 354 461.0 6 482 268 451 349 235 462 374 106.3 6 21 23 12 11 17 45 22 12.5 6 Dose Level: 0.03 30 23 38 53 35 36 45 46 37 6.3 4 40 13.0 4 Dosage unit: mg/kg/day 855 144 2 999 104 4 1284 153 2 365 77 5 976 120 3 384.3 35.4 1.5 4 4 4 169 137 166 273 191 58.2 4 440 666 421 310 459 149.3 4 14 44 18 20 24 13.6 4 Dose Level: 0.15 55 58 25 20 46 38 35 45 54 91 70 45 48 15.9 6 50 23.8 6 Dosage Unit. mg/kg/day 721 154 10 1042 127 1 733 117 .3 878 73 6 1359 103 6 643 239 3 896 136 5 267.3 57.3 3.2 6 6 6 176 138 140 143 222 287 184 59.7 6 339 451 339 436 407 240 369 78.9 6 29 6 fil 39 42 65 40 21.7 6 579 ANIMAL NUMBER ------ Group: 4 iOS506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 individual Clinical chem@stry Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS GGT SDH IU/L IU/L --------- -------- IU/L -------- - IU/L ------ IU/L ------- cx ANYLASE IU/L IU/L -------- ------- LIPASE p IU/L U/ -------- ---- Dose Level: 0.75 29 20 33 35 54 87 46 36 so 43 48 54 43 10.0 6 46 23.0 6 Dosage Unit: mg/kg/day 1772 149 3 564 112 2 967 169 2 798 138 2 808 85 2 1069 197 2 996 142 2 417.0 39.9 .4 6 6 6 154 164 436 143 329 473 283 149.7 6 675 536 626 539 349 409 522 124.7 6 38 9 21 35 20 30 26 10.9 6 580 Appendix 4 individual Clinical Chemistry Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITU PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MML/L -------- Group: I 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 KEAN S.D. N Dose Level: 0 10.3 7.0 11.0 6.7 10.6 7.0 10.5 6.8 10.4 7.4 10.7 5.1 10.6 .25 6 6.7 .80 6 Dose Level: 0.03 12.9 9.0 10.8 6.8 10.5 6.5 10.7 5.2 11.2 1.12 4 6.9 1.58 4 Dose Level: 0.15 11.2 5.4 11.2 7.4 11.4 6.4 10.9 6.9 10.4 8.3 10.6 6.3 11.0 .39 6 6.8 1.00 6 Dosage Unitt mg/kg/day 161 5.4 114 163 5.8 115 155 5.3 112 158 5.2 115 159 5.2 114 165 5.8 122 160 3.6 6 5.4 .28 6 115 3.4 6 Dosage unit: mg/kg/day 180 6.6 121 162 6.2 114 160 5.1 116 158 5.2 ill 165 10.1 4 5.9 .74 4 116 4.2 4 Dosage Unit: mg/kg/day 159 5.1 114 161 5.3 116 162 5.6 114 163 6.1 116 163 5.0 115 iss 5.9 115 160 3.1 6 5.6 .38 6 115 .9 6 581 Appendix 4 individual-Clinical Chemistry Data Males Day 37 26-WEEK CAPSULE TOXICITY SRUDY 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: 4 105506 105507 105509 105511 1055l2 105522 MEAN S.D. N Dose Level: 0.75 10.6 7.8 10.6 5.1 10.9 6.1 10.6 5.2 11.3 7.8 11.6 7.6 10.9 .43 6 6.6 1.29 6 Dosage Unit: mg/kg/day 164 5.1 119 ise 5.1 ill 162 5.4 115 157 5.8 114 162 5.5 114 166 5.7 113 162 3.4 6 5.4 .29 6 114 2.7 6 582 ANIMAL NUMBER ------ Group: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 .105548 105552 MEAN S.D. N Appendix 4 Individual Clinical Chemistry Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOWIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS GLU UN CREAT T PRO ALB GLOB T BILI SBA CHOL MG/DE, MG/DL MG/DL G/DL G/DL G/DL MG/DL UMOL/L MG/DL -------- ---------------- -------- -------- -------- ---------------- -------- Dose Level: 0 50 21 06 25 57 25 43 16 59 27 55 18 se 14.7 6 22 4.4 6 Dose Level- 0.03 87 20 65 22 65 18 50 25 67 15.2 4 21 3.0 4 Dose Level. 0.15 53 22 60 21 72 15 64 17 48 20 60 25 60 8.4 6 20 3.6 6 Dosage Unit.-mg/kg/day .9 1.3 1.2 1.1 1.1 ..9 1.1 .16 6 9.2 9.0 0.5 9.6 10.6 9.1 9.3 .71 6 4.5 4.8 4.4 4.0 4.5 4.5 4.4 .26 6 Dosage Unit: mg/kg/day 1.1 9..1 4.4 1.1 93 4.4 1.0 8.4 4.4 1.1 9.2 4.7 1.1 .05 4 9.0 .41 4 4.5 .15 4 Dosage Unitt mg/kg/day 1.0 9.4 4.4 1.0 9.0 4.7 1.1 9.0 3.9 1.0 9.4 4.7 1.0 8.9 4.0 1.0 9.5 4.0 1.0 .04 6 9.2 .26 6 4.3 .37 6 4.7 4.2 4.1 5.6 6.1 4.6 4.9 .80 6 4.7 4.9 4.0 4.5 4.5 .39 4 5.0 4.3 5.1 4.7 4.9 5.5 4.9 .40 6 1.1 .4 .8 .3 .6 .2 .6 .34 6 .4 .8 .2 .5 .5 .25 4 .7 .4 .7 .6 .4 .5 .6 .14 6 8 106 8 154 7' 160 7 183 8 127 8 151 8 147 .5 26 6 6 5 114 10 130 10 137 10 116 9 124 2.5 11 4 4 8 146 7 105 7 149 15 162 7 11 7 12 8 13 3.2 2 6 583 ANIMAL NUMBER ------ Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 Individual Clinical Chemistry Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID GLU UN CREAT T PRO ALB GLOB T BILI SHA MG/DL MG/DL MG/DL G/DL G/DL G/DL MG/DL UNOL/L -------- -------- -------- -------- -------- -------- -------- ----- -- CHOL NO/DL -------- DoSe Level: 0.75 Dosage Unit: mg/kg/day 86 27 1.1 9.2 4.3 4.9 .3 70 19 1.3 9.1 4.3 4.8 .3 77 15 1.1 9.6 4.3 5.3 .3 58 21 1.0 9.0 4.5 4.5 .4 74 30 1.2 8.7 4.5 4.2 .4 56 22 .9 8.9 4.4 4.5 .7 70 22 1.1 9.1 4.4 4.7 .4 11.5 5.4 .14 .31 .10 .39 .15 6 6 6 6 6 6 6 9 136 6 130 7 102 6 121 7 138 6 113 7 123 1.2 14 6 6 584 ANI14AL NUMBER ------ Group: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 Individual Clinical Chemistry Data Females Day 37 26-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 ------- ANYLASE LIPASE IU/L IU/L -------- -------- p U/ ---- Dose Level: 0 28 36 54 108 33 51 44 38 44 38 60 85 44 12.1 6 59 30.2 6 Dose Level: 0.03 49 73 68 81 29 51 49 76 49 15.9 4 70 13.3 4 Dose Leveli 0.15 33 35 41 69 26 49 45 125 35 70 38 60 36 6.6 6 68 30.9 6 Dosage unit: mg/kg/day 209 ea 3 400 98 9 330 so 4 583 138 7 351 164 3 298 44 5 362 102 5 125.6 42.9 2.4 6 6 6 Dosage unit: mg/kg/day 210 170 3 257 65 2 193 54 3 301 64 5 240 Be 3 48.7 54.7 1.3 4 4 4 Dosage Unit.- mg/kg/day 286 103 1 459 90 4 130 73 2 219 43 2 423 70 5 396 76 4 319 76 3 129.0 20.3 1.5 6 6 6 109 205 156 iso 274 518 240 146.6 6 287 761 165 301 378 262.2 4 206 121 110 267 123 363 198 101.3 6 376 244 326 332 494 263 339 89.9 6 254 344 423 514 394 110.9 4 364 387 305 533 317 580 414 115.1 6 14 27 38 11 le 0 is 13.2 6 24 15 23 50 28 15.2 4 41 so 36 di 0 36 34 17.4 6 585 ANIMAL NUMBER ------ Group: 4 105533 105534 105536 10@540 105542 105551 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Females Day 37 26-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 -------- cx IU/L -------- ANYLASE IU/L -------- LIPASE ZU/L -------- p U/ --- Dose Level: 0.75 34 56 37 35 42 49 37 50 22 40 45 46 36 8.0 6 46 7.5 6 Dosage Unit: mg/kg/day 305 95 543 37 743 52 269 46 296 61 332 60 415 188.9 6 58 20.0 6 1 2 2 3 3 1 2 .9 6 153 766 352 413 130 174 331 242.1 6 404 485 341 394 233 383 373 83.3 6 32 15 20 27 24 21 23 5.9 6 586 Appendix 4 Individual Clinical Chemistry Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ . CA I PHOS NA x CL MG/DL MG/DL MMOLIL MMOL/L Mt4OL/L -------- -------- -------- -------- -------- Group: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Dose Level: 0 10.5 6.8 10.8 5.6 9.7 5.0 10.6 5.6 10.6 6.4 10.2 5.0 10.4 .39 6 5.7 .73 6 Dose Level: 0.03 9.9 4.7 10.7 4.3 9.8 3.8 10.4 4.2 10.2 .42 4 4.2 .37 4 Dosage Unit: mg/kg/day 151 5.3 108 163 6.0 ill 165 6.2 120 161 5.9 117 162 5.4 iis 162 5.4 117 161 4.9 6 5.7 .38 6 115 4.4 6 Dosage Unit: mu/kg/day 154 4.0 110 166 6.2 lie 159 5.1 117 164 5.5 120 161 5.4 4 5.2 .92 4 116 4.3 4 Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D., N Dose Level: 0.15 9.2 5.5 10.0 4.9 8.5 5.2 10.5 4.0 9.7 4.9 10.2 5.9 9.7 .73 6 5.1 .65 6 Dosage Unitt mg/kg/day 159 5.0 113 154 5.3 114 156 5.3 114 160 5.0- 116 155 4.8 113 159 5.9 114 157 2.5 6 5.2 .39 6 114 1.1 6 587 Appendix 4 individual Clinical Chemistry Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ CA I PHOS MG/DL MG/DL -------- -------- NA MMOL/L -------- K CL MMOL/L MMOL/L -------- -------- Group: 4 105533 105534 105536 105540 105542 105551 KEAN S.D. N Dose Level: 0.75 10.0 5.4 10.5 4.1 10.6 4.9 10.5 5.1 10.7 5.4 10.3 4.9 10.4 .25 6 5.0 .48 6 Dosage Unit: mg/kg/day 152 5.6 114 162 5.9 117 161 5.9 117 156 6.3 115 168 6.3 122 158 5.2 114 160 5.3 6 5.9 .42 6 116 3.0 6 588 ANIMAL NUMBER ------ Group- 1 105500 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 MEAN S.D. N Appendix 4 Individual Clinical Chemistry Data Males Day 62 GLU MG/DL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULPONIC ACID MONKEYS UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI NO/DL -------- SEA UNOL/L -------- CHOL MG/DL ------- Dose Level: 0 51 71 54 56 52 70 59 9.1 6 21 17 26 16 22 17 20 3.9 6 Dosage unit: mg/kg/day 1.1 9.1 4.7 1.2 9.3 4.8 1.1 8.4 4.7 1.0 8.3 4.4 1.0 8.1 4.7 1.1 8.2 4.4 1.1 .08 6 8.6 .50 6 4.6 .17 6 4.4 4.5 3.7 3.9 3.4 3.8 4.0 .42 6 1.3 1.0 .4 .8 .3 .3 .7 .42 6 8 11 11 8 a 10 9 1.5 6 132 179 178 124 147 Ise 153 23 6 Dose Level: 0.03 Dosage Unit: mg/kg/day 56 is 1.2 8.6 4.9 3.7 .5 13 14'. 62 17 1.3 9.9 4.0 5.1 .4 8 12 61 25 1.0 8.4 4.2 4.2 .3 10 9 57 is 1.3 9.3 5.0 4.3 .3 9 8 59 20 1.2 9.0 4.7 4.3 .4 10 11 2.9 3.7 .14 .69 .36 .58 .10 2.2 2 4 4 4 4 4 4 4 4 Dose Level: 0.15 58 16 59 14 83 16 84 19 62 22 54 24 67 13.3 6 18 3.9 6 Dosage Unit: mg/kg/daY 1.1 .8 1.3 1.2 1.3 1.2 9.8 4.9 8.1. 4.1 9.0 4.8 9.0 5.4 9.4 4.4 9.2 4.3 1.2 .19 6 8.8 .42 6 4.6 .48 6 3.9 4.0 4.2 3.6 4.0 4.9 4.1 .44 6 .9 .3 .3 ..3 .5 .5 .5 .23 6 9 18 a 14 10 .14 13 13 10 13 9 13 10 14 1.7 1 6 589 ANIMAL NUMBER ------ Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Males Day 62 GLU MG/DL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNO140toGUS MONKEYS tIN 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: 0.75 68 le 95 23 71 is 67 17 71 22 70 17 74 10.6 6 19 2.6 6 Dosage Unitt mg/kg/day 1.3 8.2 4.4 1.4 9.1 4.5 1.2 9.3 5.1 1.1 6.8 4.3 1.4 8.4 4.9 1.2 8.8 5.7 1.3 .12 6 8.8 .41 6 4.8 .53 .6 3.8 4.6 4.2 4.5 3.5 3.1 4.0 .59 6 .3 10 106 .3 8 104 .3 14 117 .4 6 125 .2 11 144 .3 9 155 .3 10 125 .06 2.7 20. 6 6 6 590 ANIMAL NUMBER ------ Group: I 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group.- 2 105514 ,iOS515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 HEM S.D. N Appendix 4 individual Clinical Chemistry Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS GGT SDH cx ANYLASS LIPASE p IU/L IU/L IU/L IU/L IU/L IU/L IU/L IU/L u -------- -_:------ -------- -------- -------- -------- -------- -------- --- Dose Level: 0 34 24 44 47 45 27 24 21 33 27 33 59 36 7.9 6 34 15.2 6 Dose Level: 0.03 26 16 43 57 38 40 34 28 35 7.2 4 35 17.5 4 Dose Level: 0.15 44 41 23 20 38 31 41 40 49 .55 47 33 40 9.4 6 37 11.7 6 Dosage Unit: mg/kg/daY 709 154 4 512 102 8 742 125 9 848 77 5 1455 209 9 767 114 5 839 130 7 321.9 46.2 2.3 6 6 6 Dosage unit: mg/kg/day 634 121 5 955 109 5 1125 147 2 287 87 5 750 116 4 369.9 25.0 1.5 4 41 4 Dosage Unit: mg/kg/day 643 143 10 980 134 1 698 109 3 790 80 6 1181 106 9 535 194 2 806 128 5 237.8 39.4 3.8 6 6 6 116 144 148 82 143 156 132 27.8 6 93 173 201 129 149 47.7 4 127 157 133 175 152 173 153 19.9 6 510 280 448 365 197 428 371 115.8 6 359 641 383 331 428 143.3 4 305 442 327 436 354 203 344 89.3 6 is 47 9 it 20 27 22 13.9 6 11 38 9 27 21 13.8 4 14 0 32 24 23 26 20 11.3 6 591 ANIMAL NUMBER ------ Group- 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Males' Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC ACID MONKEYS AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L ------ - AMYLASE LIPASE p IU/L IU/L u -------- -------- -- Dose Level: 0.75 26 28 27 31 36 64 43 38 34 34 35 63 34 6.3 6 43 16;2 6 Dosage Units mg/kg/day 1502 139 462 96 626 127 683 127 725 89 941 171 823 367.0 6 125 29.9 6 4 2 2 2 3 3 3 .8 6 155 163 300 169 189 244 203 57.2 6 657 496 593 516 340 390 499 119.4 6 38 14 15 20 8 40 22 13.4 6 592 Appendix 4 individual Clinical Chemistry Data males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ CA NO/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- MMOL/L -------- CL IML/L -------- Group- 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 KEAN S.D. N DoSe Level: 0 10.0 6.8 10.8 6.9 10.6 7.6 10.0 6.4 10.9 8.2 10.3 6.8 10.4 .39 6 7.1 .66 6 Dose Level: 0.03 10.0 6.8 11.0 7.2 10.3 7.5 10.7 5.5 10.5 .44 4 6.8 .88 4 Dose Level: 0.15 10.6 5.3 10.1 7.4 10.7 6.6 10.4 7.2 10.2 7.8 10.1 5.3 10.4 .26 6 6.6 1.08 6 Dosage Unit: mg/kg/day 159 161 157 ise 159 165 160 2.9 6 4.7 S.7 5.7 5.4 5.0 5.8 5.4 .44 6 116 118 121 120 121 123 120 2.5 6 Dosage unit: mg/kg/day 160 iss 159 161 166 12.5 4 5.1 7.0 5.2 5.2 5.6 .92 4 117 136 116 120 122 9.3 4 Dosage Unit: mg/kg/day 158 4.9 121 154 4..9 115 161 61 120 162 5.1 121 161 5.8 120 164 5.3 126 160 3.5 6 5.4 .50 6 120 3.5 6 593 Appendix 4 individual Clinical Chemistry Data males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SMFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID ANIMAL NUMBER ------ . CA I PHOS NA ' x CL MG/DL MG/DL MMOL/L MMOL/L MML/L -------- -------- -------- -------- -------- Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Dose Level: 0.75 10.0 7.6 10.3 6.2 10.1 5.9 10.1 5.1 11.1 8.7 11.4 7.3 10.5 .60 6 6.8 1.31 6 Dosage Unit: mg/kg/day 159 5.3 121 153 5.6 lie 158 5.3 121 152 4.7 115 163 6.5 123 169 6.0 120 159 6.4 6 5.6 .63 6 120 2.8 6 594 ANIMAL NUMBER ------ Group: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 Individual Clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICIRY STUDY W17H PERFLUOROOCTAME POTASSIUM SALR (PFOS: T-6295) IN CYNOMOLGUS SULFORIC MONKEYS ACID GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALE G/DL -------- GLOB G/DL -------- T BILI MO/DL -------- SBA UMOL/L -------- CHOL MG/DL -------- Dose Level: 0 Dosage Units mg/kg/day 51 18 .9 8.5 4.4 4.1 .9 a 93 69 22 1.2 8.6 4.5 4.1 .3 9 152 61 25 1.2 8.5 4.5 4.0 .7 a 176 47 16 1.2 9.5 4.2 5.3 .4 9 227 67 24 1.2 9.8 4.o 5.8 .6 9 126 46 22 1.0 9.3 4.5 4.8 .3 10 156 57 21 1.1 9.0 4.4 4.7 .5 10.2 3.5 .13 .57 .21 .75 .24 6 6 6 6 6 6 6 9 155 .8 45 6 6 Dose Levels 0.03 Dosage Units mg/kg/day 92 19 1.1 9.2 4.4 4.8 .4 7 126 62 23 1.1 9.2 4.2 5.0 .8 8 130 58 19 1.0 8.3 4.3 4.0 .3 15 140 54 26 1.1 6.7 4.4 4.3 .8 12 113 66 22 1.1 8.9 4.3 4.5 .6 10 127 17.3 3.4 .05 .44 .10 .46 .26 3.7 11 4 4 4 4 4 4 4 4 4 Dose Levels 0.15 Dosage Unit: mg/kg/day 53 20 1.2 9.2 4.7 4.5 .8 10 148 60 20 1.0 9.1 4.6 4.5 .4 9 113 76 18 1.1 8.9 4.0 4.9 .8 6 153 79 16 .9 9.0 4.4 4.6 .4 15 153 48 20 1.0 8.8 4.0 4.8 .5 13 112 57 24 1.0 9.1 4.0 5.1 .6 9 145 62 20 1.0 9.0 4.3 4.7' .6 10 137 12.6 2.7 .10 .15 .33 .24 .18 3.2 19 6 6 6 6 6 6 6 6 6 595 ANIMAL NUMBER ------ Group: 4 105533 105534 105S36 105540 105542 105551 MEAN S.D. N Appendix 4 Individual clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS GLU UN CREA;R T PRO ALD GIDL GLOB G/DL T BILI MG/DL SBA UNOL/L CHOL MG/DL MG/DL -------- MG/DL -------- MG/DL -------- G/DL -------- -------- -------- -- ----- -------- ------- Dose Level: 0.75 Dosage unit: mg/kg/day Be 19 1.2 8.8 4.4 44..48 ..35 9 139 9 142 73 20 1.4 9.5 4.7 14 1.2 9.6 4.3 5.3 .2 9 101 75 68 is 1.1 9.0 4.5 4.5 4.3 .4 .3 12 148 6 120 74 19 1.2 8.5 4.2 1.0 8.7 4.4 4.3 .4 8 69 29 74 205.0 1..213 9..044 4..417 4..639 ..410 7.2 6 6 6 6 6 6 6 9 127 1.9 is 6 6 596 ANIMAL NLTMBER ------ Group: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUG SULPONIC ACID MONKEYS AST/SGOT ALT/SGPT ALK PHOS GGT SDH CK AWfLASS LIPASE p IU/L IU/L IU/L IU/L IU/L IU/L IU/L IU/L u -------- -------- -------- -------- -------- -------- -------- -------- --- Dose Level: 0 Dosage Unitt mg/kg/day 35 49 38 49 32 45 39 39 41 49 40 86 38 3.4 6 53 16.7 6 Dose Level: 0.03 245 86 2 331 92 6 321 83 5 665 170 6 290 159 2 309 48 4 360 106 4 152.5 47.7 1.8 6 6 6 Dosage Unit% mg/kg/day 182 226 490 294 245 138 262 123.6 6 352 272 346 330 498 251 342 86.9 6 11 5 38 5 26 0 14 14.7 6 55 77 241 ISO 41 98 239 67 33 60 186 53 51 73 297 66 3. 316 244 27 2 334 296 0 4 182 410 12 7 270 483 38 45 9.9 4 77 15.8 4 241 45.3 4 84 44.5 4 4 276 358 2.2 67.9 108.3 4 4 4 19 16.7 4 Dose Level: 0.15 Dosage Unit: mg/kg/day 35 46 29 48 33 33 37 7.8 6 31 87 43 105 41 54 60 29.3 6 233 451 129 202 428 386 305 134.0 6 99 89 72 39 68 el 75 20.8 6 2 302 365 5 124 381 3 121 271 4 253 528 4 142 310 4 224 605 4 194 410 1.0 76.1 129.7 6 6 6 41 35 30 11 0 53 29 19.6 6 597 AN3:MAL NUMBER Group: 4 105533 105534 105536 105540 105542 105551 MP-AN s D. N Appendix 4 Individual Clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLTIOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MON M S ASTISGOT ALT/SGPT IU/L IU/L -------- -------- Dose Level: 0.75 ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- Dosage Unit: mg/kg/day CK IU/L -------- ANYLASE IU/L -------- LIPASE ZU/L -------- p u --- 29 35 31 31 19 43 31 7.8 6 39 41 44 52 33 42 42 6.2 6 285 506 755 240 250 351 398 200.5 6 96 39 52 48 52 62 58 20.0 6 2 2 1 2 2 2 2 .4 6 172 285 204 483 113 200 243 130.1 6 414 503 340 434 241 377 385 89.4 6 30 di 23 34 is is 27 919 6 598 Appendix 4 Individual Clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS POTASSIUM SALT (PPOS; T-6295) IN CYNONOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ CA I PHOS NA K CL NG/DL NG/DL MNOL/L NHOL/L MMOL/L -------- -------- -------- -------- -------- Group: I 105529 105530 105531 105535 105544 105549 MEAN S.D. N Groupt 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Dose Level: 0 9.7 5.9 9.6 6.2 10.4 5.9 10.3 6.5 9.9 5.7 10.3 5.5 10.0 .34 6 6.0 .36 6 Dose Level: 0.03 9.7 4.8 10.2 4.2 10.0 4.4 9.9 4.8 9.9 .22 4 4.6 .30 4 Dose Level: 0.15 9.7 5.2 10.0 4.8 8.8 5.3 10.1 4.3 9.9 5.2 9.4 5.8 9.6 .48 6 5.1 .51 6 Dosage Unit: mg/kg/day 151 4.7 114 159 6.3 114 166 6.0 123 167 6.1 125 160 5.5 119 168 6.0 125 162 6.5 6 5.8 .59 6 120 5.1 6 Dosage Units mg/kg/day 159 4.9 120 163 5.6 119 156 4.8 lie 160 5.6 123 160 2.9 4 5.2 .43 4 120 2.2 4 Dosage unit: mg/kg/day 166 6.5 127 156 5.4 121 160 5.6 127 158 5.5 121 158 4.7 122 162 5.1 121 160 3.6 6 5.5 .60 6 123 3.0 6 599 Appendix 4 Individual Clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFMIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ . CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MML/L -------- CL MMOL/L -------- Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Dose Level: 0.75 9.9 5.0 10.8 4.6 11.0 5.1 9.4 5.2 10.4 4.7 10.0 5.4 10.2 .60 6 5.0 .30 6 Dosage Unit: mg/kg/day 157 5.4 118 163 6.9 121 160 6.2 119 157 5.8 121 164 5.1 119 165 5.3 123 161 3.5 6 5.8 .67 6 120 1.8 6 600 ANIMAL NUMBER ------ Group-. I 105508 105517 105519 105520 105526 105527 ME" S.D. N' Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS GLU UN CREAT T PRO ALB MG/DL -------- MG/DL -------- MG/DL -------- G/DL -------- G/DL -------- GLOB G/DL ---- T BILI MG/DL SBA UMOL/L ------ CHOL MG/DL ------- Dose Level: 0 53 64 57 54 56 74 60 8.0 6 19 19 29 19 17 20 20 4.3 6 Dosage Unit; mg/kg/day 1.0 8.7 4.7 1.3 9.1 4.8 1.1 8.3 4.7 1.0 8.4 4.7 1.1 8.3 4.8 1.3 9.2 5.0 1.1 .14 6 6.7 .40 6 4.8 .12 6 4.0 4.3 3.6 3.7 3.5 4.2 3.9 .33 6 1.2 1.1 .5 .8 .3 .4 .7 .38 6 6 119 8 177 9 170 a 132 7 isi 9 177 8 154 1.2 24 6 6 Dose Levelt 0.03 Dosage Unit: mg/kg/daY 57 19 1.2 9.0 5.1 3.9 1.2 10.3 5.2 5.1 .6 .3 74 14 1.1 8.5 5.1 3.4 .4 64 59 26 19 1.6 10.5 5.9 4.6 .4 64 20 1.3 9..698 5..339 4..275 ..413 7.6 4.9 .22 4 4 4 4 4 4 4 7 143 a 132 7 109 8 119 8 126 .6 14 4 4 Dose Level: 0.15 Dosage Unit: mg/kg/daY 65 is 1.2 8.7 5.1 3.6 70 1149 11..03 99..00 45..90 44..10 108 78 16 1.0 9.1 5.2 3.9 75 26 1.4 8.8 4.8 4.0 53 22 1.2 9.2 5.0 4.2 .8 8 173 .3 6 163 .2 8 125 .3 9 139 .5 14 13 1 .5 6 161 75 19 1.2 9.0 5..014 4..021 ..422 9 2.7 18.5 4.6 .16 .19 6 6 6 6 6 6 6 6 601 ANIMAL NUMBER ------ Group: 4 105506 iOS507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 individual clinical Chemistry Data males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC W)NKEYS ACID GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB O/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA UNOL/L -------- CHOL MG/DL -------- Dose Level- 0.75 Dosage unit: mg/kg/day 63 20 1.6 99..58 55..51 44..70 ..32 9 107 8 80 ill 21 1.6 75 18 1.3 9.8 5.4 4.4 .3 17 90 62 le 1.1 9.0 4.7 4.3 .3 9 105 6635 2l0e 11..43 99..05 55..35 34..70 ..23 107 114471 73 19.1 6 19 1.3 6 1.4 .19 6 9.4 .36 6 5.2 .31 6 4.2 .35 6 .3 10 112 .05 3.6 27 6 6 6 602 Appendix 4 Individual Clinical Chemistry Data ANIMAL NUM13ER Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOST T-6295) IN CYNOMOLGUS SULPONIC ACID MONKEYS AST/SGCYr IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT ZU/L -------- SDH iu/L --- ---- CK ANYLASE LIPASE p IU/L IU/L IU/L U/ -------- -------- -------- ---- Group% 1 105508 105517 105519 105!520 105!526 105!527 MEAN S.13. N Group: 2 IOSS14 105515 105516 105521 MEAM S.D. N Group.- 3 105505 105510 105518 105523 105524 105528 MEAN S.13. N Dose Level: 0 41 25 48 45 46 31 27 24 36 24 36 63 39 7.7 6 35 15.8 6 Dose Level: 0.03 26 16 35 38 37 46 43 142 35 7.0 4 60 55.8 4 Dose Level: 0.15 46 39 25 21 41 37 34 38 45 87 61 49 42 12.2 6 45 22.4 6 Dosage Unit: mg/kg/daY 706 533 782 901 1408 863 866 296.2 6 152 102 130 82 226 126 136 50.1 6 4 6 11 7 9 5 7 2.6 6 Dosage Unitt mg/kg/day 692 127 5 824 113 4 1306 181 2 335 104 5 789 131 4 401.7 34.5 1.4 4 4 4 Dosage Unit- mg/kg/day 710 1097 645 724 1271 660 143 11 160 1 ill 4 76 11 108 4 244 3 851 140 6 265.3 58.6 4.3 6 6 6 222 164 166 120 167 168 168 32.4 6 130 153 189 227 175 42.5 4 164 137 140 129 194 220 164 36.2 6 525 275 437 377 251 487 392 111.8 6 386 741 396 338 465 185.6 4 356 501 324 454 394 235 377 94.9 6 18 23 0 20 53 84 33 30.3 6 10 134 30 le 48 57.9 4 38 5 25 25 12 56 27 18.3 6 603 AN114AL NUMBER Group: 4 IOSS06 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 Individual Clinical Chemistry Data males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS AST/SGOT ALT/SGPT IU/L IU/L -------- -------- ALX PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- ANYLASE IU/L -------- LIPASS IU/L -------- p u --- Dose Level: 0.75 29 21 30 34 40 75 43 35 31 34 41 65 36 6.3 6 44 21.0 6 Dosage Unit: mg/kg/day 1624 463 563 566 726 900 154 108 122 lie 95 166 807 428.6 6 127 27.4 6 3 2 2 1 2 2 2 .6 6 133 174 305 204 157 308 214 75.7 6 730 556 409 345 353 414 468 149.1 6 63 is 26 35 is 38 32 17.5 6 604 Appendix 4 individual Clinical Chemistry Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANI14AL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MOL/L -------- x MOL/L -------- CL MOL/L -------- Group: 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group- 3 105505 105510 105518 105523 105524 105528 MEAN S.D. N Dose Level: 0 9.7 6.9 11.0 6.3 9.8 6.6 10.2 6.7 9.5 6.9 11.4 7.4 10.3 .77 6 6.9 .37 6 Dose Level: 0.03 9.8 10.1 10.6 11.6 6.9 6.7 7.5 5.8* 10.5 .79 4 6.7 .70 4 Dose Level: 0.15 11.0 5.8 11.4 8.2 10.0 6.6 10.7 6.s 10.4 8.0 10.3 5.8 10.6 .51 6 6.8 1.05 6 Dosage Unit: mg/kg/day 158 160 154' 156 159 174 160 7.1 6 4.7 5.1 4.7 5.2 4.9 6.2 5.1 .56 6 115 117 112 lid 119 127 117 5.3 6 Dosage Unit: mg/kg/day 163 173 163 169 167 4.9 4 4.6 6.8 5.1 6.4 5.7 1.04 a 117 125 117 123 120 4.1 4 Dosage 160 169 159 160 162 .155 unit: mg/kg/day 4.8 117 5.6 129 5.3 115 5.7 122 5.7 110 5.3 112 161 4.6 6 5.4 .35 6 lie 7.0 6 605 Appendix 4 individual Clinical Chemistry Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULF014IC ACID MONKEYS ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- x MMOL/L -------- CL MMOL/L -------- Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Dose Level: 0.75 10.7 7.1 11.2 6.7 10.4 5.6 10.3 5.0 11.2 6.6 11.1 7.5 10.8 .41 6 6.4 .94 6 Dosage Unit: mg/kg/day 170 5.1 125 160 5.8 114 158 5.1 117 ise 5.0 116 163 5.2 115 167 6.1 114 163 5.0 6 5.4* .45 6 117 4.2 6 606 ANIMAL NUMBER ------ Group- 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105546 105552 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS MCNKKYS GLU un CREA!T T PRO ALB GLOB T BILI SBA CHOL MG/DL MG/DL MG/DL G/DL G/DL G/DL MG/DL UMOL/L MG/DL. -------- -------- -------- -------- -------- -------- -------- -------- -------- Dose Level- 0 Dosage Unit: mg/kg/day 48 20 1.0 8.8 4.7 4.1 .7 8 99 78 22 1.3 9.8 5.4 4.4 .3 6 189 95 21 1.2 8.5 4.5 4.0 .4 10 182 58 15 1.2 9.4 4.4 5.0 .3 7 217 78 22 1.1 9.7 4.4 5.3 .5 9 136 42 18 1.1 9.3 4.7 4.6 .3 9 171 66 20 1.2 9.2 4.7 4.6 .4 20.5 2.7 .10 .51 .38 .51 .16 6 6 6 6 6 6 6 8 166 1.5 42 6 6 Dose Level: 0.03 Dosage Unit: mg/kg/day el is 1.1 9.0 4.7 4.3 51 22 1.2 9.8 4.7 5.1 61 22 1.0 8.1 4.3 3.8 80 26 1.1 9.0 4.6 4.4 .3 7 114 .9 7 143 .4 8 149 .4 10 129 68 22 1.1 9.0 4.6 4.4 .5 14.7 3.3 .08 .69 .19 .54 .27 4 4 4 4 4 4 4 8 134 1.4 15 4 4 Dose Level.-0.15 Dosage Unit: mg/kg/day 62 15 1.1 9.2 4.8 4.4 .6 7 153 55 20 1.1 9.3 4.9 4.4 .3 74 le 1.0 9.7 3.8 4.9 .4 7 122 a 143 49 14 1.0 8.9 4.6 4.3 .5 22 151 45 17 1.0 9.0 4.3 4.7 .4 10 125 74 26 1.0 9.3 4.2 5.1 .4 a 143 60 20 1.0 9.1 4.4 4.6 .4 10 140 12.4 4.2 .05 .24 .41 .32 .10 5.8 13 6 6 6 6 6 6 6 6 6 607 ANIMAL NUMBER ------ Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 individual Clinical ChemistrY Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID GLU UN CREAI T PRO ALB GLOB T BILI SBA MG/DL MG/DL MG/DL G/DL G/DL G/DL MG/DL UNOL/L -------- -------- -------- -------- -------- -------- -------- ---- --- CHOL MG/DL -------- Dose Level: 0.75 Dosage Unit: mg/kg/day 84 22 1.2 9.8 4.8 5.0 89 is 1.4 9.5 5.0 4.5 89 14 1.2 9.6 4.5 5.1 63 20 1.4 10.0 5.2 4.8 93 32 1.3 9.1 4.5 4.6 56 26 .9 8.8 4.6 4.2 .3 9 142 .3 6 131 .3 6 65 .3 13 105 .3 7 115 .5 24 109 79 22 1.2 9.5 4.8 4.7 .3 11 ill 15.5 6.3 .19 .45 .29 .33 .08 7.0 26 6 6 6 6 6 6 6 6 6 608 ANIMAL NUMBER ------ Group% 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. n Group: 3 105532 105538 105539 105545 105548 105552 HFJM S.D. N Appendix 4 Individual Clinical Chemistry Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ASTISGOT ALT/SGPT IU/L IU/L -------- -------- Dose Level: 0 ALK PHOS IU/L -------- OGT IU/L -------- SDH IU/L -------- Dosage Unit: mg/kg/day CR IU/L -------- ANYLHSE IU/L -------- LIPASE ZU/L -------- p u --- 36 55 57 70 35 43 53 39 40 38 44 74 44 9.1 6 54 17.9 6 Dose Level: 0.03 220 81 3 322 123 9 292 84 6 583 161 7 274 164 5 264 50 4 329 110 6 128.7 46.5 2.2 6 6 6 Dosage Unit: mg/kg/day 188 1481 128 2407 146 368 786 947.2 6 387 292 410 350 sio 269 370 87.4 6 8 0 45 10 25 0 15 17.5 6 39 72 39 go 30 50 64 114 43 14.6 4 79 26.6 4 Dose Level: 0.15 219 220 2 238 73 2 169 53 3 307 67 11 233 103 4 S7.5 78.3 4.4 4 4 4 Dosage Unit. mg/kg/day 247 250 165 217 220 39.4 4 269 349 454 487 390 99.8 4 23 2 23 25 is 10.9 4 30 37 23 56 38 40 37 11.1 6 34 57 52 153 54 54 67 42.8 6 235 531 157 229 404 390 324 140.3 6 98 85 69 42 68 82 74 19.2 6 1 196 4 149 3 107 2 345 7 230 7 227 4 209 2.5 81.8 6 6 447 426 290 520 329 640 442 127.6 6 130 41 26 25 0 is 40 46.1 6 09 ANIMAL NUMBER ------ - Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Females Day 91 26-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 -------- ANYLASE IU/L -------- LIPASE IU/L -------- p U/ ---- DoSe Level: 0.75 35 43 38 34 33 42 31 41 20 40 50 71 34 9.8 6 45 13.0 6 Dosage Unit: mg/kg/day 296 106 447 43 668 54 294 52 280 59 346 63 388 150.1 6 63 22.3 6 1 1 2 2 2 2 2 .5 6 1132 476 367 141 105 276 416 377.0 6 389 402 343 480 225 353 379 96.5 6 35 0 18 35 16 12 19 13.6 6 610 Appendix 4 individual Clinical chemistry Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUN SALT (PFOS; T-6295) IN CYNONOLGUS SULPONIC NONKEYS ACYD ANINAL NUNBER ------ CA NG/DL -------- I PHOS NG/DL -------- NA NKOL/L -------- K NHOL/L -------- CL NNOL/L -------- Group: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group.- 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Dose Level: 0 10.2 5.5 11.1 6.0 10.3 4.8 11.0 6.8 8.1 5.6 10.7 5.5 10.2 1.11 6 5.7 .66 6 Dose Level: 0.03 9.7 4.5 11.5 3.6 8.8 4.5 10.9 4.0 10.2 1.21 4 4.2 .44 4 Dose Level: 0.15 9.7 5.4 10.7 5.0 9.2 5.4 10.1 4.1 10.4 5.2 9.9 6.0 10.0 .53 6 5.2 .63 6 Dosage unit: mg/kg/day 151 5.0 109 168 6.7 125 160 5.1 116 166 5.7 125 160 4.8 lie 162 6.1 117 161 5.9 6 5.6 .74 6 lie 6.1 6 Dosage Unit: mg/kg/day 156 170 154 165 161 7.5 4 4.6 6.5 4.5 5.4 5.2 .93 4 110 122 113 124 117 6.0 4 Dosage Unit: mg/kg/day 160 5.2 116 161 6.2 121 156 5.3 116 156 5.6 lie' 160 5.7 125 165 6.3 125 160 3.4 6 5.7 .45 6 120 4.2 6 611 Appendix 4 individual Clinical CheRistry Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOT-GUS MONKEYS ANIMAL NUMBER ------ . CA MG/DL -------- I PHOS MG/DL -------- 14A MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 4 105533 105534 105536 105540 X05542 105551 MEAN S.D. N Dose Level: 0.75 10.4 4.9 10.5 4.2 10.7 5.0 11.5 5.8 10.6 5.3 9.7 5.2 10.6 .58 6 5.1 .53 6 Dosage unit: mg/kg/day 159 5.4 122 165 6.2 124 160 59 114 170 6:6 117 163 5.9 lie 157 5.1 115 162 4.7 6 5.8 .54 6 lie 3.9 6 612 ANIMAL NLTHEER Group: 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group:. 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 1055D5 105510 105518 105523 105524 105528 MEAN S.t). N Appendix 4 Individual Clinical Chemistry Data Males Day 153 GLU MG/DL 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS UN CREAT T PRO ALB GLOB T BILI SBA CHOL MG/DL MG/DL G/DL G/DL G/DL MG/DL UMOL/L MO/DL M( -------- -------- -------- -------- -------- -------- -------- -------- DoSe Level. 0 Dosage Unit: mg/kg/day 57 22 74 16 52 25 55 19 60 20 65 20 60 8.0 6 20 3.0 6 Dose Level: 0.03 56 18 63 19 60 22 66 17 61 4.3 4 19 2.2 4 Dose Level: 0.15 1.0 7.7 4.6 1.2 8.9 5.0 1.1 7.9 4.7 1.0 8.2 4.6 1.2 8.1 5.0 1.3 8.6 4.9 1.1 .12 6 8.2 .45 6 4.8 .19 6 Dosage Unit: mg/kg/day 1.1 8.3 5.0 1.3 9.6 5.2 1.1 7.9 5.0 1.5 9.4 5.5 1.2 .19 4 8.8 .83 4 5.2 .24 4 Dosage Units mg/kg/d&3@ 3.1 3.9 3.2 3.6 3.1 3.7 3.4 .34 6 3.3 4.4 2.9 3.9 3.6 .66 4 1.2 1.2 .4 .6 .4 .3 .7 dl 6 .5 .3 .4 .4 .4 .08 4 8 11 12 11 9 10 10 1.5 6 7 a a 6 7 10 4 115 178 183 124 147 178 156 29.9 6 136 127 117 98 120 16.3 4 59 21 1.1 8.4 5.3 3.1 .7 11 191 62 16 .9 8.2 4.7 3.5 .3 7 135 71 24 1.3 9.3 5.4 3.9 .4 10 145 74 17 1.1 9.6 4.7 4.9 .2 9 129 65 27 1.4 8.5 5.0 3.5 .6 11 136@ 48 2S 1.1 8.6 4.6 3.8 .6 14 157 63 22 1.2 8.8 5.0 3.8 .5 10 149 9.4 4.5 .18 .55 .31 .61 .20 2.3 22.8 6 6 6 6 6 6 6 6 6 613 ANIMAL NUMBER ------ Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOtr-US MONKEYS ACID GLU MG/DL UN MG/DL CREAT T PRO ALB GLOB T BILI SEA CHOL TR -M-G-/-DL---- --G-/-DL---- --G-/-DL---- --G-/-D-L--- --MG-/-DL---- -U-N-O-L/-L--- -M-G-/-DL---- MG/ -------- -------- Dose Levelt 0.75 Dosage Unit: mg/kg/day 80 2223 11..46 99..40 54..48 44..02 :22 1141 5279 4.8 .3 17 65 98 6550 2171 11..20 99..00 44..26 4.4 .3 a 75 91 19 1.2 8.7 5.1 3.6 72 19 1.3 9.2 5.4 3.8 .2 24 76 .2 13 87 76 20 1.3 9.0 4.9 4.1 2 14 65 17.0 2.2 .20 .23 .48 .43 :05 6 6 6 6 6 6 6 5.5 20.3 6 6 614 ANIMAL NUMBER ------ Group; 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOSI T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID AST/SGOT IU/L -------- ALT/SGPT IU/L -------- A@K PHOS IU/L -------- GGT IU/L -------- SDH ZU/L -------- CK IU/L -------- AKYLASE IU/L -------- LIPASE IU/L -------- p u --- Dose Level: 0* Dosage Unit: mg/kg/day 29 31 34 51 37 29 23 22 30 30 33 95 31 4.9 6 43 27.3 6 Dose Level: 0.03 723 156 2 490 125 2 666 128 8 842 79 3 1370 230 1 659 126 1 792 142 3 305.3 53.1 2.6 6 6 6 Dosage Unit: mgikg/day 157 130 194 135 184 191 165 28.5 6 527 290 457 408 226 446 392 112.8 6 28 27 12 20 12 39 23 10.5 6 22 13 35 59 35 43 28 28 30 6.3 4 36 19.8 4 Dose Level: 0.15 606 132 4 778 109 3 1093 163 1 258 88 1 684 123 2 340.2 32.2 1.5 4 4 4 Dosage Unit: mg/kg/day 92 144 lee 108 133 42.6 4 403 713 420 344 470 165.2 4 14 100 19 31 41 40.0 4 43 28 33 20 50 63 40 15.7 6 72 43 40 36 75 63 55 17.2 6 740 848 720 897 1241 673 853 207.5 6 160 143 129 70 121 262 148 63.8 6 4 219 348 30 1 178 514 9 2 201 356 36 1 122 479 28 7 213 402 36 8 225 475 860 4 193 429 266 3.1 38.4 69.9 339.9 6 6 6 6 615 ANIMAL NUMBER ------ Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Males Day 153 26-WEEK CAPSULE TOXIDITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS AST/SGOT ALT/SGPT ALK PHOS GGT SDH IU/L IU/L IU/L IU/L IU/L ----- -- -------- -------- -------- ---- --- CK ANYLASE LIPASE IU/L IU/L IU/L -------- -------- - ------ p U/ ---- Dose Level: 28 31 52 44 40 37 39 9.8 6 0.75 24 39 85 33 46 85 52 26.6 6 Dosage Unit: mg/kg/day 1262 168 239 109 902 88 415 98 377 70 683 141 646 384.1 6 112 36.1 6 2 2 5 2 2 2 2 1.2 6 180 219 954 207 267 285 352 297.5 6 758 499 504 494 439 406 517 124.5 6 61 9 25 33 25 36 32 17.2 6 616 Appendix 4 individual Clinical Chemistry Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE 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: I 105508 105517 IOSS19 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 iOS516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 MEAN S.D. N Dose Level: 0 9.0 6.6 11.0 6.2 10.3 6.8 9.8 6.9 9.9 6.9 10.8 6.3 10.1 .73 6 6.6 .31 6 Dose Level: 0.03 10.2 6.6 11.3 6.6 10.4 7.2 11.2 4.7 10.8 .56 4 6.3 1.09 4 Dose Level: 0.15 9.6 5.7 10.1 7.2 11.3 6.9 10.9 6.2 9.9 8.6 10.3 6.5 10.4 .64 6 6.8 1.01 6 Dosage Unit: mg/kg/day 154 4.7 116 160 5.4 116 150 5.3 110 151 5.3 112 163 5.0 121 164 6.1 119 157 6.1 6 5.4 .48 6 116 4.1 6 Dosage unit: mg/kg/day 154 5.0 113 163 6.1 114 159 4.9 118 161 6.1 122 159 3.9 4 5.5 .67 4 117. 4.1 4 Dosage unit: mg/kg/day 161 5.7 120 154 4.8 119 159 6.0 114 158 5.3 116 161 5.6 109 154 5.8 112 158 3.2 6 5.5 .43 6 115 4.2 6 617 Appendix 4 individual Clinical Chemistry Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MCNYMS ACID ANIMAL NLMBER ------ . CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- IK MMOL/L ------ - CL MMOL/L -------- Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Dose Level: 0.75 11.4 7.9 10.4 6.7 9.5 4.3 10.5 5.9 11.4 9.1 11.3 7.2 10.8 .76 6 6.8 1.66 6 Dosage unit: mg/kg/day 171 6.6 120 150 64 ill 153 4:8 107 153 5.8 108 160 51 109 163 6:2 114 158 7.9 6 58 :73 6 113 7.8 6 618 ANIMAL NUMBER ------ Group: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Appendix 4 Individual Clinical Chemistry Data Females Day 153 GLU MG/DL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL ---- --- T BILI SBA CHOL TR MG/DL UMOL/L MO/DL NO/ -------- -------- -------- --- DoSe Level: 0 48 21 74 22 62 25 57 16 57 23 47 is 58 9.9 6 20 4.0 6 Dose Level: 0.03 46 18 70 25 72 12 68 24 64 12.1 4 20 6.0 4 Dose Level: 0.15 49 20 53 23 62 18 59 24 58 23 60 27 57 4.9 6 22 3.1 6 Dosage Unit: mg/kg/day .9 7.6 4.3 1.3 9.6 5.6 1.2 8.2 4.6 1.2 9.2 4.4 1.1 9.4 4.6 1.1 9.3 4.8 1.1 .14 6 8.9 .80 6 4.7 .47 6 Dosage unit: mg/kg/day 1.0 8.6 4.4 1.3 8.9 4.6 .9 8.3 3.8 1.1 8.5 4.7 1.1 .17 4 8.6 .25 4 4.4 .40 4 Dosage unit-. mg/kg/day 1.1 9.2 5.1 1.0 8.5 4.6 1.2 8.8 4.2 1.0 8.3 4.7 1.1 8.7 4.3 1.0 9.0 4.1 1.1 .08 6 8.8 .33 6 4.5 .37 6 3.3 4.0 3.6 4.8 4.8 4.5 4.2 .63 6 4.2 4.3 4.5 3.8 4.2 .29 4 4.1 3.9 4.6 3.6 4.4 4.9 4.2 .48 6 1.0 .3 .6 .4 .6 .3 .5 .27 6 .4 10 :2 .5 .5 .34 4 .6 .3 .4 .5 .4 .6 .5 .12 6 7 9 9 9 9 11 9 1.3 6 80 175 177 226 143 175 163 48.5 6 6 9 10 9 a 1.7 4 102 128 82 127 110 22.1 4 8 7 9 12 is 8 10 3.1 6 133 100 144 136 107 162 130 23.2 6 619 ANIMAL NUMBER ------ Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 Individual Clinical Chemistry Data Females Day 153 GLU MG/DL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 ------- -------- -------- -------- --- ---- ---------------- -- ----- TRI MG/I ----- Dose Level: 0.75 el 21 74 12 70 13 62 15 07 18 46 26 70 14.6 is 5.3 Dosage Unit: mg/kg/day 1.2 9.6 5.1 1.4 9.1 4.6 1.1 9.0 3.9 1.1 8.7 4.6 1.1 8.4 4.2 1.0 8.6 4.6 1.2 .14 8.9 .43 4.5 .41 4.5 4.5 5.1 4.2 4.2 4.0 4.4 .40 .3 is 100 .3 9 128 .2 6 62 .3 8 80 .4 9 77 .4 43 99 .3 15 91 .09 13.8 23.1 6 6 620 Appendix 4 individual Clinical Chemistry Data Females Day 153 ANIMAL NUMBER 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS AST/SGOT ALT/SGPT ALK PHOS GGT SDH cx ANYLASE LIPASE p IU/L IU/L ZU/L u IU/L -------- IU/L -------- IU/L -------- IU/L -------- IU/L -------- -------- -------- -------- Group-. I 105529 105530 OS 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Dose Level: 0 52 159 33 82 30 51 31 48 37 44 33 79 36 8.2 6 77 43.3 6 Dose Level: 0.03 54 Be 33 70 17 18 46 146 38 16.2 4 so 52.8 4 Dose Level: 0.15 36 47 31 53 24 38 61 131 26 75 38 52 36 13.4 6 66 34.1 6 Dosage Unit: mg/kg/day 175 78 3 305 115 1 277 82 2 593 171 2 266 176 1 272 53 2 315 143.3 6 112 51.2 6 2 .8 6 Dosage Unit: mg/kg/day 221 2S4 3' 233 70 2 280 42 2 312 68 1 262 42.2 4 108 97.8 4 2 .8 4 Dosage Unit: mg/kg/day 259 100 2 498 78 3 169 68 3 228 38 2 401 67 1 292 70 0 308 72 3 120.9 20.3 2.5 6 6 6 192 377 156 362 155 169 235 105.0 6 395 293 79 253 255 131.7 4 268 lie 201 330 126 412 242 116.5 6 395 296 383 361 499 302 373 74.3 6 249 358 394 513 376 108.9 4 371 405 280 494 310 733 432 165.5 6 11 45 8 25 0 is 17.7 5 25 3 11 33 le 13.5 4 23 45 34 28 0 19 25 15.2 6 621 ANI14AL NUMBER Group: 4 105533 105534 105536 105540 105'542 105551 MEAN S.D. N Appendix 4 Individual clinical Chemistry Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID AST/SGOT ALT/SGPT IU/L IU/L -------- -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH. IU/L -------- CK IU/L -------- A14YLASE IU/L -------- LIPASE p IU/L u ------ -- Dose Level: 0.75 33 45 73 42 34 41 30 40 22 62 46 60 40 18.1 6 48 10.0 6 Dosage unit: mg/kg/day 285 107 1 359 44 2 616 47 7 230 44 2 216 57 1 310 66 1 336 61 2 146.9 24.2 2.3 6 6 6 297 3173 99 139 154 306 695 1217.1 6 374 554 344 404 232 373 380 104.1 6 33 6 23 36 31 30 26 10.9 6 622 Appendix 4 individual Clinical Chemistry Data Females Day 153 26-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 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: .2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105549 105552 MEAN S.D. N Dose Level: 0 9.4 5.2 11.7 6.0 10.1 5.8 10.7 5.8 10.1 5.2 9.4 5.8 10.2 .87 6 5.6 .34 6 Dose Level: 0.03 8.4 4.0 10.9 4.9 10.0 3.0 10.0 4.6 9.8 1.04 4 4.1 .84 4 Dose Level: 0.15 9.5 5.0 9.3 3.8 9.7 5.7 9.9 4.0 10.4 5.1 10.2 6.3 9.0 .42 6 5.0 .96 6 Dosage Unit: mg/kg/day 144 4.7 107 169 6.6 124 155 5.8 116 163 6.9 125 159 5.6 125 161 6.5 116 158 8.5 6 6.0 .81 6 119 7.2 6 Dosage Unit: mg/kg/day 148 163 151 159 155 6.9 4 5.1 6.1 5.3 5.8 5.6 .46 4 108 lie 113 124 116 6.8 4 Dosage unit: mo/kg/day 153 4.7 110 152 53 lie 154 5:8 115 152 57 114 158 4:8 120 154 5.9 lie 154 2.2 6 5.4 .52 6 116 3.6 6 623 Appendix 4 Individual Clinical Chemistry Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLOUS SULPONIC MONKEYS ACID ANI14AL NUMBER ------ CA NO/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K 14MOL/L -------- CL "MOL/L -------- Group: 4 105533 105534 105536 105540 105542 105551 S.D. N Dose Level: 0.75 10.6 5.0 11.7 6.0 10.5 5.0 10.1 4.0 10.6 4.3 9.7 5.3 10.5 .67 6 4.9 .71 6 Dosage Unit: mg/kg/day 158 5.3 116 166 7.1 lit 153 7.1 116 153 5.9 ill 161 6.5 124 156 5.7 114 158 5.0 6 6.3 .75 6 116 4.4 6 624 ANIMAL NUMBER ------ Group: 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group. 3 105505 105510 105518 105523 105524 105528 MEAN S.D. N Appendix 4 individual Clinical Chemistry Data Males Day 182 GLU MG/DL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID UN CREAT MG/DL MG/DL -------- ------- T PRO O/DL -------- ALB O/DL ------- GLOB O/DL ----- -- T BILI SBA CHOL TR MG/DL UMOL/L MG/DL MG/ -------- -------- -------- ---- DoSe Level: 0 64 le 68 14 51 25 59 16 57 21 64 17 60 6.1 6 18 3.9 6 Dose Level: 0.03 62 18 77 12 59 27 57 16 64 9.1 4 18 6.3 4 Dose Level: 0.15 70 15 71 13 83 le 69 16 72 19 57 20 70 8.3 6 17 2.6 6 Dosage Unit: mg/kg/day 1.1 8.5 4.9 1.2 9.1 4.9 1.0 7.7 4.6 .8 7.7 4.5 1.2 8.4 5.1 1.2. 9.1 4.6 1.1 .16 6 8.2 .54 6 4.8 .23 6 Dosage unit: mg/kg/day 1.2 8.6 4.9 1.2 9.1 4.8 1.0 8.0 4.8 1.4 9.5 5.5 1.2 .16 4 8.8 .65 4 5.0 .34 4 Dosage Unit: mg/kg/day 1.1 .8 1.2 1.1 13 1:1 1.1 .17 6 8.6 8.2 8.5 9.0 8.4 8.2 8.5 .30 6 5.2 4.4 5.0 5.2 4.8 4.7 4.9 .31 6 3.6 4.2 3.1 3.2 3.3 3.5 3.5 .40 6 3.7 4.3 3.2 4.0 3.8 .47 4 3.4 3.8 3.5 3.9 3.6 3.5 3.6 .17 6 .9 .8 .5 .5 .3 .4 .6 @23 6 .3 .2 .4 .3 .3 .08 4 .5 .2 .3 .3 .4 .4 .4 .10 6 5 7 5 6 6 6 6 .8 6 127 166 186 112 165 158 IS2 27.5 6 5 4 5 s 5 .5 4 135 104 98 102 110 17.0 4 a 190 5 136 7 119 5 137 5 151 5 149 6 147 1.3 24.0 6 6 625 ANIMAL NUMBER ------ Groupt 4 105506 a 105507 105511 105512 105522 MEAN S.D. N Appendix 4 Individual Clinical Chemistry Data Males Day 182 GLU MG/DL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID UN CREAT MG/DL MG/DL -------- ------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA CHOL UNOL/L . MG/DL -------- -------- TR MG/ ---- I)ose Levelt 0.75 Dosage unie: mg/kg/day 107 28 1.8 9.2 4.4 4.8 93 22 1.4 98..30 44..82 43..58 2 58 67 :2 28 28 .2 le 59 66 78 23 .9 27 1.3 8.8 5.2 3.6 .2 7 38 69 67 16 1.4 9.8 5.4 4.4 .3 19 76 22 1.2 9.0 4.9 4.1 .2 le 48 .05 8.6 18.8 12.6 4.5 .24 .477 .453 .44 4 4 -4 4 4 4 4 a Unscheduled sacrifice on Day 179. 626 ANI:MAL NU14BER Group: 1 105508 105517 IOSS19 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105529 HFAN S.D. N Appendix 4 individual Clinical Chemistry Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ASTISG(YR ALT/SGPT ZU/L IU/L -------- ------- AIX PHOS IU/L -------- GGT IU/L -------- SDH ZU/L -------- CK IU/L -------- A14YLASE IU/L -----7 -- LIPASE p ZU/L U/ -------- --- Dose Level: 0 28 32 35 52 41 27 23 26 30 26 33 69 32 6.2 6 39 17.9 6 Dose Level.: 0.03 19 16 34 35 29 34 27 31 27 6.2 4 29 8.8 4 Dosage Unit: mg/kg/day 756 169 2 420 126 5 628 149 10 776 72 3 1322 266 7 510 118 11 735 150 6 318.7 65.6 3.7 6 6 6 Dosage Unit: mg/kg/day 548 136 2 552 100 6 1085 182 2 233 87 4 604 126, 4 353.5 42.6 1.9 4 4 4 122 106 526 207 159 140 210 158.7 6 93 219 143 96 130 59.8 4 524 308 440 388 243 454 393 102.8 6 379 6&6 391 354 442 136.5 4 15 37 19 30 22 51 29 13.4 6 is 37 is 27 24 10.6 4 Dose Level: 0.15 30 39 21 20 39 51 22 58 50 69 51 43 36 13.3 6 47 16.9 6 Dosage unit.: mg/kg/day 650 171 4 634 133 3 558 115 7 697 95 3 1035 125 13 557 250 5 688 148 6 178.3 55.6 3.8 6 6 6 lie 102 116 101 296 314 174 101.5 6 412 431 336 472 397 240 381 82.3 6 36 7 36 36 37 27 30 11.6 6 627 AN114AL NUH13ER Group- 4 105506 a 10!5507 105511 105512 105522 MEAN S.D . N Appendix A Individual Clinical Chemistry Data Males Day lB2 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS AST/SGOT ALT/SGPT ALK PHOS GGT SDH cx ANYLASE LIPASE p IU/L IU/L U/ IU/L -------- IU/L -------- IU/L -------- IU/L IU/L ZU/L ------- --- ---- --- -- Dose Level: 0.75 73 29 30 46 41 25 36 44 30 73 34 5.3 4 47 19.7 4 Dosage Unit-. mg/kg/day 876 134 10 208 110 2 3&4 101 4 422 71 3 581 132 2 389 104 3 25.3 1.0 4 4 4040 192 101 175 256 182 64.5 4 738 474 524 379 408 446 65.3 4 67 17 27 32 68 36 22.2 4 a Unscheduled sacrifice on Day 179. 628 Appendix A individual Clinical chemistry Data males Day 102 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA --MM-O-L/-L--- K CL .M.K.OL./.L... .M.M.OL./.L... Group: 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 MEAN s.ii. N Dose Level: 0 10.1 10.9 10.2 9.1 10.5 9.9 6.8 5.5 .6.5 6.2 7.7 5.6 10.2 .43 6 6.4 .82 6 Dose Level: 0.03 9.9 5.7 9.9 5.3 9.9 7.1 10.3 4.9 10.0 .20 4 5.8 .96 4 Dose Level: 0.15 10.8 5.0 9.7 6.5 10.2 6.1 10.2 6.3 10.1 7.5 9.7 5.8 10.1 .41 6 6.2 .82 6 Dosage unit: mg/kg/day 156 160 149 151 159 iso 4.7 5.3 5.2 5.2 5.2 4.9 ill 113 112 109 112 110 154 4.8 6 5.1 .23 6 III 1.5 6 Dosage Unit: mg/kg/day 157 5.1 112 155 4..9 107 154 4 .7 109 157 54 108 156 1.5 4 5.0 .32 4 109 2.2 4 Dosage Unit: mg/kg/day 157 4.0 112 152 &..9 113 147 54 107 158 5.2 112 158 5.2 110 150 4.8 106 154 4.7 6 5.0 .25 6 110 2.9 6 629 Appendix 4 individual Clinical Chemistry Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CA I PHOS NA Ix CL MG/DL -------- MG/DL -------- MMOL/L -------- MMOL/L -------- MML/L -------- Group: 4 105506 a 105507 105511 105512 105522 HEM S.D. N Dose Level; 0.75 10.6 6.9 10.1 7.2 9.6 4.4 10.3 6.1 11.1 6.7 10.3 .62 4 6.1 1.22 4 Dosage Unit: mg/kg/day 157 7.5 ill 144 55 99 152 5:2 ill 157 56 109 158 5:4 106 153 6.4 4 5.4 .17 4 106 5.3 4 a Unscheduled sacrifice on Day 179. 630 ANIMAL NUMBER ------ Group: I 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 HEA14 S.D. N Appendix 4 Individual Clinical Chemistry Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS MONKEYS GLU UN CREAT T PRO ALB GLOB T BILI SBA CHOL T G/DL MG/DL UMOL/L MG/DL 14G MG/DL -------- MG/DL -------- MG/DL -------- G/DL -------- G/DL -------- -------- -------- -------- -------- Dose Level: 0 35 23 58 21 68 22 44 16 75 22 65 14 58 15.2 6 20 3.7 6 Dose Level: 0.03 62 18 58 18 53 19 44 25 54 7.8 4 20 3.4 4 I)ose Level: 0.15 80 17 63 17 66 is 56 21 55 16 66 24 64 9.0 6 19 3.1 6 Dosage unit: mg/kg/day .8 8.0 4.4 1.3 9.6 5.5 1.2 8.4 4.5 1.2 9.4 4.7 1.2 9.5 4.4 1.0 0.7 4.6 1.1. .18 6 8.9 .66 6 4.7 .42 6 Dosage Unit- mg/kg/day 1.1 1.2 .8 1.0 1.0 .17 4 9.1 9.3 7.6 8.5 8.6 .76 4 4.6 4.7 3.7 4.6 4.4 .47 4 Dosage unit: mg/kg/day 1.1 9.2 5.0 .9 8.6 4.6 1.1 9.0 4.3 1.0 8.4 4.7 .9 8.5 4.3 1.0 9.6 4.0 1.0 .09 6 8.9 .47 6 4.5 .35 6 3.6 4.1 3.9 4.7 5.1 4.1 4.2 .55 6 4.5 4.6 3.9 3.9 4.2 .38 4 4.2 4.0 4.7 3.7 4.2 5.6 4.4 .67 6 .9 .3 .4 .3 .4 .2 .4 .25 6 .5 .8 .2 .5 t .24 4 .4 .3 .4 .5 .3 .3 .4 .08 6 5 87 6 181 6 176 6 226 7 143 6 149 6 160 .6 46.5 6 6 4 99 6 143 4 109 7 138 5 122 1.5 21.6 4 4 10 7 6 11 7 7 8 2.0 6 130 98 154 137 108 149 129 22.3 6 631 ANIMAL NUMBER ------ Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 Individual Clinical Chemistry Data Females Day 182 GLU MG/DL -------- 26-WEEK CAPSULE TOXICITY SRUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID UN CREAT MG/DL MG/DL -------- -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL ------ - SBA CHOL TR UNOL/L MG/DL MG/ -------- -------- ---- Dose Level: 0.75 78 23 74 22 86 12 67 le 80 22 55 25 73 11.0 6 20 4.7 6 Dosage Unit: mg/kg/day 1.2 9.1 4.8 1.4 9.4 4.8 1.2 9.9 4.0 1.1 9.1 4.7 1.1 9.2 4.4 .9 8.8 4.6 1.2 .16 6 9.2 .37 6 4.6 .31 6 4.3 4.6 5.9 4.4 4.8 4.2 4.7 .63 6 .2 .2 .2 .3 .2 .4 2 :08 6 5 6 5 12 4 11 7 3.4 6 Be 93 67 76 66 102 82 14.7 6 632 Appendix 4 individual Clinical Chemistry Data Females Day 182 ANIMAL NUMBER Group- I 105529 105530 105531 105535 105544 105549 MEAN S.D. N Group- 2 105537 105541 105547 105550 MEAN S.D. N Grc)up: 3 105532 105538 105539 105545 105548 105552 MF.AN S.D. N 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID AST/SGOT ALT/SGPT ALK PHOS GGT SDH CK ANYLASE LIPASE p IU/L IU/L u IU/L IU/L IU/L -------- -------- IU/L ------- IU/L --- ---- IU/L --- ---- -------- ---- -------- Dose Level: 0 91 262 @30 55 25 42 37 56 39 61 26 47 41 25.0 6 87 85.9 6 Dooe Level: 0.03 58 61 34 60 26 55 50 ill 42 14.6 4 72 26.3 4 Dose Level; 0.15 34 38 29 32 21 43 59 126 42 35 35 43 37 13.0 6 53 36.1 6 Dosage Unit: mg/kg/day 169 274 243 554 237 222 283 137.1 6 Dosage 86 10 113 2 al 4 172 5 182 7 48 2 114, 5 53.3 3.1 6 6 Unit: mg/kg/day 207 218 296 236 239 39.7 4 Dosage 260 3 70 2 50 5 65 is ill 6 99.5 6.0 4 4 Unit-. mg/kg/day 228 363 118 219 303 295 254 85.3 6 102 69 74 41 65 76 71 19.7 6 5 5 2 3 14 13 7 5.2 151 197 04 287 134 422 212 123.4 6 2745 209 147 190 823 1281.8 4 167 95 238 321 109 164 182 84.7 6 350 282 407 351 530 345 378 84.6 6 254 337 347 496 3S8 . 100 7 4 372 430 302 514 335 683 439 140.9 6 19 16 103 14 41 0 32 37.1 6 14 12 8 41 19 15.0 4 56 52 42 29 0 17 33 21.6 6 633 ANIMAL NUMBER ------ Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Appendix 4 individual Clinical ChemiStrY Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS AST/SGOT ALT/SGPT ALK PHOS GGT IU/L IU/L IU/L IU/L -------- -------- -------- -------- SDH IU/L ---- --- CK ANYLASE LIPASE p IU/L IU/L IU/L U/ -------- -------- -------- ---- Dose Leveli 0.75 33 43 33 34 31 38 25 37 32 59 44 53 33 6.2 6 44 9.9 6 Dosage Unit: mg/kg/daY 243 107 4 245 43 1 659 58 4 217 48 2 212 63 5 320 65 4 316 64 3 172.4 22.7 1.5 6 6 6 253 203 189 296 515 251 284 119.3 6 337 467 408 399 279 358 375 64.9 6 j9 9 19 68 42 20 31 21.2 6 634 Appendix 4 individual Clinical Chemistry Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CA I PHOS NA K CL MG/DL -------- MG/DL -------- MMOL/L -------- MOL/L -------- MMOL/L -------- Group: 1 105529 105530 105531 105535 105544 105549 KEAN S.D. N Group: 2 105537 105541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N Dose Level: 0 9.1 4.5 11.1 6.1 9.8 5.2 10.6 6.1 10.2 5.7 10.1 4.1 10.2 .68 6 5.3 .84 6 Dose Levelt 0.03 9.2 4.2 .10.9 4.2 9.1 5.0 9.4 4.3 9.6 .84 4 4.4 .39 4 Dose Level: 0.15 9.7 5.4 9.6 3.3 9.8 5.8 9.9 3.7 9.6 4.6 10.0 5.9 9.6 .16 6 4.8 1.10 6 Dosage Unit: mg/kg/day 142 159 155 159 160 158 156 6.8 6 4.5 61 5 :1 50 5:,1 5.7 5.3 .56 6 102 112 108 112 115 115 ill 5.0 6 Dosage unit: mg/kg/day 148 3.9 106 163 6.1 114 149 4.5 110 149 4.5 107 152 7.2 4 4.8 .94 4 109 3.6 4 Dosage unit: mg/kg/day iss 4.8 110 149 4..4 108 155 51 110 156 5.1 112 151 5.0 113 .158 5.5 110 154 3.3 6 5.0 .37 6 110 1.6 6 635 Appendix 4 individual Clinical Chemistry Data Females Day 182 26-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 -------- MML/L -------- CL MML/L -------- Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Dose Leveli 0.75 9.3 4.7 10.8 5.3 10.9 5.3 9.9 4.4 11.0 6.6 10.0 5.0 10.3 .69 6 5.2 .76 6 Dosage unit: mg/kg/day 148 4.3 109 160 6.6 113 162 5.9 112 155 5.0 106 158 5.7 107 155 4.9 113 156 4.9 6 5.4 .82 6 110 3.1 6 636 ANIMAL NUMBER ------ Group- I 105520 105526 MEAN S.D. GroUp: 3 105505 z05523 MEAN S.D. n Group: 4 lossii 105S22 MEAN S.D. N APPENDIX 4 individual Clinical Chemistry Data . males Day 217 CLU MG/DL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT FPFOS; T-629S) IN CYNOMOLCUS UN KG/DL -------- CREAT MG/DL -------- T PRO C/DL -------- ALE G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA UMOL/L -------- CHOL MG/DL -------- TRIC MG/D ----- U@ose Level: 0 S9 12 55 19 57 2.8 2 16 4.9 2 Dome Level: O.lS 61 17 79 17 70 12.0 2 17 .0 2 Z)ose Level: 0.75 70 13 76 16 73 4.2 2 14 2.1 2 Dosage Unit: mglkg/day 1.1 7.9 4.6 1.0 8.2 4.7 1.0 .07 2 8.0 .21 2 4.6 .07 2 Dosage Unit: mg/kg/day .8 8.7 5.1 1.0 9.3 S.1 .9 9.0 5.1 .14 .42 .00 2 2 2 Dosage Unit: mg/k(j/day 1.0 a.7 4.3 1.1 8.7 4.8 1.0 .07 2 8.7 .00 2 4.6 .3S 2 3.3 3.5 3.4 .14 2 3.6 4.2 3.9 .42 2 4.4 3.9 4.2 .35 2 .6 .4 .5 .14 2 .8 .5 .6 .21 2 .6 .6 .6 .00 2 11 13 12 1.4 2 112 152 132 28.3 2 16 16 16 .0 2 184 131 iss 37.S 2 12 17 14 3.5 2 140 134 137 4.2 2 APPENDIX 4 Individual clinical Chemistry Data Males Day 217 ANIMAL NUMBER 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT IPFOS; T-62951 IN CYNOMOLGUS AST/SCOT ZU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -- ----- SDH IU/L -------- CK IU/L ------- ANYLASE LIPASE IU/L IU/L -------- -------- P ANY U/L ------ Group: I ioSS20 105526 HEAII S.DN Group: 3 rOSS05 105523 MEAN S.DN Group: 4 iossii ZOSS22 MEAN S.D. N Dose Level: 0 19 23 24 28 22 3.S 2 26 3.5 2 Dose Level: 43 31 0.15 45 42 37 8.5 2 44 2.1 2 Dose Level: 0.75 36 28 29 68 32 4.9 2 48 28.3 2 Dosage Unit: mg/kg/day 709 62 3 llS6 237 4 932 iso 4 316.1 123.7 .7 2 2 2 Dosage unit: mg/kglday 917 186 11 669 89 13 793 175.4 2 138 68.6 2 12 1.4 2 Dosage Unit-. mg/kg/day 538 127 1 499 159 2 Sig 143 2 27.6 22.6 .7 2 2 2 84 194 139 77.8 2 177 146 162 21.9 2 177 223 200 32 s 2 400 276 338 97.7 2 424 484 454 42.4 2 543 467 S05 S3.7 2 30 2 41 2 36 2 7.9 2 48 45 46 2.1 2 23 53 38 21.2 2 APPENDIX 4 Individual clinical Chemistry Data Males Day 21'7 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS, T-6295) IN CYNOMOLGUS ACID ANIMAL NUMBER ------ Group: 1 iOS520 105526 I.IEAII S.D. 11 Group: 3 105505 iD5523 HEAII S.D. li Group: 4 105511 IOSS22 MEAN S.D. N CA MG/DL -------- I PHOS MG/DL -------- NA M14OL/L ---- K CL MMOL/L MMOL/L - -------- Dose Level: 0 9.6 10.4 10.0 .57 2 5.5 7.1 6.3 1.13 2 Dose Level: O.lS 11.5 10.4 11.0 .78 2 6.6 6.6 6.6 .00 2 Dose Level: 0.*15 10.6 10.9 10.8 .21 2 5.4 7.0 6.2 1.13 2 Dosage Unit: mg/ka/day ISO 4.6 112 IS4 5.3 110 152 2.8 2 5.0 .49 2 111 1.4 2 Dosage Unit: mg/kg/diy 156 5.5 110 154 S.1 106 iss 1.4 2 5.3 .29 2 log 2.8 2 Dosage unit: mg/kg/daY 157 161 159 2.8 2 5.4 5.5 5.4 .07 2 112 110 ill 1.4 2 AVIIKAL NUMBER Group: I 105529 105549 MEAN S.D. Group: 3 105539 105552 MEAN S.D. N Group: 4 105533 ZOSS42 MEAN S.D. N APPENDIX 4 individual Clinical Chemistry Data Females Day 217 CLU MG/DL 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIU14 SALT (PFOS; T-629S) IN CYNOMOLGUS UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALE G/DL -------- GLOB C/DL -------- T BILI MG/DL -------- SBA Lq4OL/L -------- CHOL MG/DL -------- TRI MG/D ----- Dose Level: 0 51 19 67 12 59 11.3 2 16 4.9 2 E)ose Level: O.LS 76 19 77 16 76 .7 2 is 2.1 2 ]Dose Level: 0.75 82 21 68 25 7S 9.9 2 23 2.8 2 Dosage Unit: mg/kg/day .7 8.3 4.4 .9 8.9 4.7 .8 8.6 4.6 .14 .42 .21 2 2 2 Dosage Unit: mo/kg/day 1.0 1.0 1.0 .00 2 8.6 8.8 8.7 .14 2 4.1 4.0 4.0 .07 2 Dosage Unit: mg/kg/day 1.1 9.6 5.0 .9 9.0 4.2 1.0 .21 2 9.3 .42 2 4.6 .57 2 3.9 4.2 4.0 .21 2 4.5 4.8 4.6 .21 2 4.6 4.9 4.7 .14 2 .7. .1 .4 .42 2 .6 .6 .6 .00 2 .6 s .6 .07 2 13 15 14 1.4 2 86 152 119 46.7 2 14 13 14 .7 2 142 149 145 4.2 2 14 24 19 7.1 2 135 131 133 2.8 2 APPENDIX 4 AIIIHAL NUMBER Group: 1 IOSS29 TOSS49 HEAti S.D11 Group: 3 IOSS39 IOSS52 HEA14 S.DN Group: 4 105533 105542 MEAN S.D. N individual Clinical chemistry Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) Ili CYNOMOLGUS AST/SGOT IU/L ----- -- ALT/SGI-r IU/L -------- ALK PHOS IU/L -------- GGT - I-U-/-L--- SDH IU/L -------- CK AMYLASE LIPASS ZU/L ZU/L IU/L -------- -------- -------- P AM U/L ----- Dose Level: 0 35 120 34 86 34 .7 2 103 24.0 2 Dose Level: 0.15 19 43 33 54 26 9.9 2 48 . 78 2 Dose Level: 0.75 23 38 23 61 23 .0 2 50 16.3 2 Dosage Unit: mci/ka/day 161 81 4 208 41 5 184 61 4 33.2 28.3 .7 2 2 2 Dosage unit: mg/ko/day 113 69 1 251 72 7 182 70 4 97.6 2.1 4.2 2 2 2 Dosage Unit: mg/kg/day 241 121 2 200 68 5 220 94 4 29.0 37.5 2.1 2 2 2 157 117 137 . 29 3 2 117 1197 657 763.7 2 144 186 165 29.7 2 377 309 343 48.1 2 313 658 486 244.0 2 394 296 345 69.3 2 26 0 13 18.4 2 48 17 32 21.9 2 3S Al 38 4.2 2 APPENDIX 4 individual Clinical chemistry Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-629S) IN CYNOMOLCUS ANI14AL 14UMBER ------ CA I PHOS 14A MG/DL MG/DL M14OL/L -- ----- ----- -- -------- T, CL M14OL/L tiMOL/L -------- -------- croup: I 105529 'LUS549 HEAII S.D. Dose Level: 0 9.7 5.9 9.9 3.7 9.9 - .14 2 4.8 l.s6 2 Dosaae Unit: mg/kg/day 145 5.0 103 152 5.9 112 148 4.9 2 5.4 .64 2 108 6.4 2 Group: 3 105539 IOS552 MEAN S.D. N Group: 4 105533 105542 MEAN S.D. li Dose Level: O.IS 9.9 5.7 9.7 5.3 9.8 .14 2 S.S .28 2 DOSO Level: 0.75 10.4 5.4 10.2 6.3 10.3 .14 2 5.8 .64 2 Dosage unit: mg/ka/daY iss S.S 112 ISO S.5 109 152 3.5 2 5.5 .00 2 110 2.1 2 Dosage Unit: mg/kg/day 152 5.2 ill 152 4.9 108 152 .0 2 5.0 .21 2 110 2.1 2 APPENDIX 4 ANIMAL NUMBER ------ Group: I 105S20 IOSS26 EAH Ms.D. N Croup- 3 lossos JOSS23 MEAN S.D. N Group: 4 105511 JOSS22 KEAN S.D. N individual Clinical Chemistry Data males Day 24S 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC AcrD POTASSIUM SALT (PFOS; T-6295) IN CYHOMOLCUS GLU UH CREAT T PRO ALB GLOB T BILI -M-G-/D-L---- -N-O-/D-L---- -M-G-/D-L---- G/DL -------- - G/DL ------ G/DL MG/DL -------- ------- SRA UMOL/L CHOL MG/DL TRI MG/ D -------- -------- ----- Dose Level: 0 116 is 86 17 101 21.2 2 16 1.4 2 Dose Level: 0. is 79 17 83 17 al 2.8 2 17 .0 2 Dose Level: 0.7S 61 16 84 is 72 16.3 2 17 1.4 2 Dosage Unit: mg/ko/day 1.2 8.8 4.9 1.0 8.6 4.8 1.1 .14 2 8.7 .14 2 4.8 .07 2 Dosage Unit: mg/kg/clay 1.2 1.0 1.1 .14 2 9.1 8.9 9.0 .14 2 5.3 5.2 S.2 o7 2 Dosage Unit: mg/kg/day 1.0 8.6 4.4 1.0 9.1 4.9 1.0 .00 2 8.8 .3S 2 4.6 .3S 2 3.9 3.8 3.8 .07 2 3.8 3.7 3.8 o7 2 4.2 4.2 4.2 .00 2 .5 .4 .4 .07 2 .8 .4 .6 .28 2 .4 .4 .4 .00 2 8 114 9 155 8 134 .7 29.0 2 2 5 11 a 4.2 2 193 128 160 46.0 2 7 is 11 5.7 2 132 139 136 4.9 2 ANIKAL NUMBER ------ Group- I iOSS20 105526 MEAN S.D. N Group: 3 I05sos 105523 MEAN S.D. N Group: 4 105511 105522 MEAN S.D. N APPENDIX 4 individual clinical Chanistry Data males Day 24S 26-WEEK CAPSULE TOXICITY STUDY WITN PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ACID AST/SGOT ALT/SGPT IU/L IU/L -------- -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IUIL -------- CK IU/L -------- AMYLASE IUIL -------- LIPASE IU/L -------- P AM U/L ----- Dose Level: 0 24 27 30 29 27 4.2 2 28 .7 2 Dose Level: 0.15 49 40 19 40 34 21.2 2 40 .0 2 Dose Level: 0.75 42 33 49 73 46 4.9 2 53 28.3 2 Dosage Unit: mg/kg/daY 664 68 2 1137 220 6 900 144 4 334.5 107.5 2.8 2 2 2 Dosage unit: mg/kg/daY 882 186 6 793 98 1 938 142 4 62.9 62.2 3.5 2 2 2 Dosage Unit: mg/kg/day 736 156 1 625 176 6 680 166 4 79.5 14.1 3.5 2 2 2 145 209 177 4S.3 2 409 307 359 72.1 2 189 124 156 46.0' 2 422 503 462 57.3 2 178 336 257 111.7 2 628 460 S44 118.8 2 33 52 42 13.4 2 22 52 37 21.2 2 17 48 32 21.9 2 APPENDIX 4 individual Clinical Chemistry Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS A14IMAL NUMBER ------ CA MG/DL -------- I PHOS 14G/DL -------- NA MMOL/L -------- K MMOLIL -------- CL MMOL/L -------- Group: 1 105S2O IOSS26 HEA14 S.D. Dose Level: 0 9.9 6.2 10.4 7.1 10.2 .35 2 6.6 .64 2 Dosage Unit: mg/kg/daY 152 5.0 117 157 5.0 117 154 3.5 2 S.0 .00 2 117 .0 2 Group-. 3 IOSS05 JOSS23 MEAN S.D. N Group-. 4 iossii 105522 Dose Level: 0.15 11.3 6.5 10.5 6.8 10.9 .57 2 6.6 .21 2 Dose Level: 0.75 10.4 6.2 11.3 7.8 Dosage unit: mg/kg/oay 160 5.2 lie 159 5.1 116 160 .7 2 S.2 .07 2 117 1.4 2 Dosage Unit: mg/kg/day 159 5.0 118 164 5.4 114 MEAN S.D. N 10.9 .64 2 7.0 1.13 2 162 3.5 2 5.2 .28 2 116 2.8 2 ANIMAL NUMBER Group: I 105529 iOSS49 MEAN S.D. N Group- 3 IDS539 ioSS52 MEAN S.D. N Group: 4 IOSS33 IOSS42 MEAN s.D. N APPENDIX 4 Individual Clinical chomirtry Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) in CYNOMOLOUS GLU M(;/DL um MG/DL -------- CRPAT M(;/DL -------- T PRO C/DL -------- ALE G/DL -------- GLOB G/DL -------- T BILI MC/DL -------- SBA UtIOL/L -------- CHOL FIG/DL -------- TR MG/ ---- Doze Level: 0 Dosage Unit: mg/kglday 48 20 8.S 4.S 4.0 Go is 1.2 9.4 4.7 4.7 .8 a 94 .3 10 168 se is 1.0 9.0 4.6 4.4 .6 14.1 3.5 .3S .64 .14 .49 .3S 2 2 2 2 2 2 9 131 1.4 52.3 2 2 Dos* Level: 0.15 Dosage Unit: mg/kg/day 83 19 92 21 87 S.7 2 20 1.4 2 Doze Level: 0.75 92 22 91 22 92 .7 2 22 .0 2 1.1 8.8 4.0 .9 9.2 4.2 I.o .14 2 9.0 .28 2 4.1 .14 2 DosacFe Unit: mglkg/day 1.3 9.8 5.0 1.2 9.0 4.4 1.2 .07 2 9.4 .57 2 4.7 .42 2 4.8 5.0 4.9 .14 2 4.8 4.6 4.7 .14 2 .5 12 163 .3 10 138 .4 11 iso .14 1.4 17.7 2 2 2 .2 19 isi .3 21 147 .2 is 149 .07 5.7 2.6 2 2 2 ANIMAL NUMBER ------ Group: 105529 105549 14EAII S.D. 14 Group: 3 105539 iOSS52 MEAN S.D. Group: 4 105533 IOSS42 MEAN S.D. N APPENDIX 4 individual clinical Chemistry Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTA14E SULFONIC POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS ACID AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L -------- -------- -------- GGT SDH CK AMYLASE ' LIPASE P A14 IU/L IU/L IU/L IU/L IU/L U/L - ------ -------- -------- -------- -------- ----- Dose Level: 0 42 158 29 74 36 9.2 2 116 S9.4 2 Dose Level: 0.15 24 61 37 71 30 9.2 2 66 7.1 2 Dose Level: 0.75 28 41 22 39 25 4.2 2 40 1.4 2 Dosage Unit: mg.lkg/day 160 2 203 44 3 182 58 2 30.4 20.5 .7 2 2 2 Dosage Unit; mg/kg/day 113 77 1 262 83 5 iss so 3 IOS.4 4.2 2.8 2 2 2 Dosage Unit: mg/kg/day 249 121 2 224 74 1 236 98 2 17.7 33.2 .7 2 2 2 204 132 168 SO.9 2 120 663 392 384.0 2 168 129 148 27.6 2 363 295 329 48.1 2 311 654 482 242.S 2 385 277 331 76.4 2 21 0 10 14.8 2 46 21 34 17.7 2 113 19 66 66.5 2 APPENDIX 4 individual clinical chemistry Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ------ CA NO/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MtIOL/L -------- Group: 1 105529 105549 HEAI; S.D. if Group: 3 105539 105552 MEAN S.D. N Group: 4 IOSS33 105542 MEAN S.D. N Dose Level: 0 9.6 4.8 9.8 4.4 9.7 .14 2 4.6 .28 2 Dose Level: O.lS 9.5 5.6 10.2 5.2 9.8 .49 2 S.4 .28 2 Dose Level: 0.75 10.2 11.0 10.6 .57 2 4.9 5.9 5.4 .71 2 Dosage unit: mglkg!day 147 4.5 ill 153 4.8 Lis 150 4.2 2 4.6 .21 2 114 4.9 2 Dosage Unit: mg/kg/day 148 4.9 117 iss 5.9 120 IS2 4.9 2 5.4 .71 2 118 2.1 2 Dosage Unit: mg/kg/day iss 4.8 116 166 6.2 125 160 7.8 2 5.S .99 2 120 6.4 2 APPENDIX 4 ANIMAL NUMBER ------ individual Clinical Chemistry Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOHIC ACID POTASSIUM SALT IPFOS; T-629S) IN CYNOMOLGUS GLU UN CREAT T PRO ALB GLOB T BILI sy3A CHOL TRI NO/DL MG/DL MG/DL G/IDL G/DL G/DL MG/DL UMOL/L MG/DL MG/D - -------- -------- -------- -------- -------- -------- -------- -------- -------- ----- Group: 1 105520 IOSS26 MEAN S.D. m Group: 3 105505 105523 MEAN S.D. N Group. 4 105511 105522 MEAN S.D. N Dwase Level: 0 80 13 54 is 67 18.4 2 16 3.S 2 Dose Level: 0.15 76 18 72 20 74 2.8 2 19 1.4 2 ]Dose Level: 0.75 63 20 76 is 70 9.2 2 is 3.S 2 Dosage Unit: mg/kg/day 1.3 8.8 4.8 1.1 8.2 4.6 1.2 .14 2 8.5 .42 2 4.7 .14 2 Dosage Unit: mg/kg/day .9 9.0 5.2 1.1 8.7 4.9 1.0 .14 2 8.8 .21 2 5.0 .21 2 Dosage Unit: mg/kg/day 1.0 8.8 4.5 1.3 8.9 5.1 1.2 .21 2 8.8 .07 2 4.8 .42 2 4.0 3.6 3.8 .28 2 3.8 3.8 3.8 .00 2 4.3 3.8 4.0 .35 2 .7 .1 .4 .42 2 .5 .3 .4 .14 2 .4 .2 .3 .14 2 3 112 2 149 2 130 .7 26.2 2 2 11 7 9 2.8 2 203 132 168 50.2 2 5 10 8 3.5 2 135 143 139 5.7 2 ANIMAL NUMBER ------ Group; I TOSS20 105526 HEAII S.D. Group: 3 105505 105523 MEAN S.D. N Group: 4 105511 105522 MEAN S.D. N APPENDIX 4 Individual Clinical Chemistry Data Males Day 274 26-WEEK CAPSULE ToxrciTy STUDY witm PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS: T-629S) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L -------- --------- -------- GOT IU/L -------- SDH IU/L -------- CK IU/L -------- AI.IYLASE IU/L -------- LIPASE IU/L -------- P AM U/L Dose Level: 0 19 31 37 39 28 12.7 2 35 5.7 2 Dose Level: 0.15 31 42 22 36 26 6.4 2 39 4.2 2 Dosage Unit: mg/kglday SS2 60 4 1131 188 10 842 124 7 41)9.4 90.5 4.2 2 2 2 Dosage unit: mg/kg/day 92S 195 2 776 96 6 850 146 4 105.4 70.0 2.8 2 2 2 151 201 176 35.4 2 IS7 125 141 22.6 2 368 267 318 71.4 2 414 475 444 43.1 2 31 41 36 7.1 2 41 37 39 2.9 2 Dose Level: 0.75- 41 39 36 69 38 3.S 2 S4 21.2 2 Dosage Unit: mg/kg/day $21 ise 3 SS7 169 4 689 164 4 186.7 7.8 .7 2 2 2 167 294 230 89.8 2 572 453 S12 84.1 2 la 52 35 24.0 2 APPENDIX 4 Individual Clinical chemistry Data males Day 274 26-WEEK CAPSULE 'MXICITY STUDY WITH PERFLUOROOCTAME SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS A141MAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L ------- CL MMOL/L -------- Group: 1 105520 IOSS26 14E)Ul Dose Level: 0 10.3 5.2 10.0 6.8 10.2 .21 2 6.0 1.13 2 Dosage Unit: mglkg/day 157 S.9 116 150 S.6 iis 154 4.9 2 5.8 .21 2 116 .7 2 Group: 3 IOS50S IOSS23 MEAN S.D. N Group: 4 105511 I05S22 MEAN S.D. N Dose Level: 0.15 12.0 6.2 10.3 6.S 11.2 1.20 2 6.4 .21 2 Dose Level: 0.7S 10.8 5.7 11.6 7.0 11.2 .57 2 6.4 .92 2 Dosage Unit: ova/kglday 164 5.9 123 ls4 S.4 114 ls9 7.1 2 5.6 .35 2 118 6.4 2 Dosage Unit: mg/kg/day ise 5.4 iis 163 5.9 112 160 3.5. 2 5.6 .35 2 114 2.1 2 ANIMAL NUMBER ------ Group: I 105S29 IOSS49 MEAN S.D. 1) Group: 3 IOSS39 105552 MEAN S.D. N Group-. 4 IOSS33 ZOSS42 MEAN S.D. N APPENDIX 4 individual clinical Chemistry Data Females Day 274 26-WEEK CAPSULE IMXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-629S) IN CYNOMOTGUS GLU um CREAT T PRO ALB GLOB T BILI SBA CHOL Ti IqG/DL -------- MG/DL -------- MG/DL -------- G/DL -------- C/DL -------- C/DL -------- MG/DL -------- UNOL/L -------- MG/DL -------- MG/ I)oseLevel: 0 4S 67 56 15.6 2 23 16 20 4.9 2 Dosage Unit: mg/kg/day .8 8.1 4.2 .8 9.3 4.6 .8 8.7 4.4 .00 .85 .28 2 2 2 3.9 4.7 4.3 .57 2 1.0 .2 .6 .57 2 17 10 a 2.1 2 so 170 129 59.0 2 Dose Level: 0.15 Dosage Unit: mg/kg/day 78 19 .8 8.7 4.0 4.7 .5 71 23 1.0 9..L 4.0 5.1 .2 74 21 .9 8.9 4.0 4.9 .4 4.9 2.a .14 .28 .00 .28 .21 2 2 2 2 2 2 2 Dose Level: 0.75 Dosage Unit: mg/kg/day 95 20 .9 9.2 4.7 4.5 .1 90 26 1.1 8.7 4.1 4.6 .1 92 23 1.0 9.o 4.4 4.6 .1 3.S 4.2 .14 .35 .42 .07 .00 2 2 2 2 2 2 2 5 148 5 139 5 144 .0 6.4 2 2 4 14S 7 144 6 144 2.1 .7 2 2 APPENDIX 4 ANIMAL NUMBER Grotip: I 105529 105549 MEAN S.D. Group: 3 105539 iO55S2 14EM4 S.D. N Group: 4 IOSS33 105542 MEAN S.D. N Individual Clinical Chemistry Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT IPPOS; T-629S) IN CYNOMOLGUS AST/SGOT ALT/SGPT IU/L IU/L -------- -------- ALK PHOS IU/L -------- GGT SDH CK IU/L IU/L IU/L - ------ -------- ------- AMYLASE LIPASE IU/L IU/L -------- -------- p AN U/L ----- Doze Level: U 47 128 33 79 40 9.9 2 104 34.6 2 Dose Level: 0.15 27 60 47 57 37 14.1 2 58 2.1 2 Dose Level: 0.75 42 51 16 36 29 18.4 2 44 10.6 2 Dosage Unit: mg/kg/day 138 70 2 IRA 45 4 163 58 3 35.4 17.7 1.4 2 2 2 Dosage Unit: mg/kg/day 105 77 4 238 76 14 172 '16 9 94.0 .7 7.1 2 2 2. Dosage Unit: mg/kg/day 244 208 226 25.5 2 108 66 87 29.7 2 6 4 .5 1.4 2 167 435 301 189.5 2 113 2316 1214 15S7.8 2 165 120 142 31.8 2 328 290 305 26.9 2 287 649 468 256.0 2 396 235 316 113.8 2 18 0 9 12.7 2 50 98 74 33.9 2 34 31 32 2.1 2 Appmmix 4 individual Clinical Chemistry Data Females Day 274 26-WEEK CAPSULE TOXIC3[TY STUDY WITH PERFLUOROOCTJUIE SULFONIC POTASSIUM SALT (PPOS; T-6295) 114 CYNOIIOLGUS ACID ANIMAL NUMBER --- CA NG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 105529 105549 MEAN S.D. Group: 3 IOS539 iOSS52 MEAN S.D. if Group: 4 105533 iOSS42 MEAN S.D. N Dose Level: 0 9.3 4.6 10.4 4.2 9.8 .78 2 4.4 .28 2 Dose Level: 0.15 9.5 5.3 9.S 5.2 9.5 .00 2 5.2 .07 2 t)ose Level: 0.75 10.4 S.8 10.4 4.6 10.4 .00 2 S.2 .85 2 Dosage unit: mu/ko/daY 144 4.3 107 iss 5.6 114 ISO 7.8 2 5.0 .92 2 110 4.9 2 Dosage 152 148 Unit: mg!kg/day 5.4 115 4.1 107 150 2.8 2 4.8 .92 2 ill 5.7 2 Dosage Unit: mo/ka/day IS4 6.1 121 157 6.0 117 IS6 2.1 2 6.0 .07 2 119 2.8 2 ANIMAL NUMBER ------ Group: 1 iOSS20 iOSS26 MEAN S.D. N Croup: 3 105505 105523 MEAN S.D. N Group.- 4 105511 IOSS22 MEAN S.D. N APPENDIX 4 Individual Clinical chemistry Data Males Day 322 GLU MG/DL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT IPFOS; T-6295) IN CYNOMOLGUS um -M-O-/D-L- -- cp.EAT T PRO ALB GLOB T BILI MG/DL G/DL G/DL C/DL MG/DL -------- -------- - ------ -------- ------- SBA UNOL/L CHOL MG/DL TRI MG/D -------- -------- --- - Dose Level: 0 74 19 68 16 71 4.2 2 is 2.1 2 Doge Level: O.lS 45 26 78 30 62 23.3 2 28 2.8 2 Dose Level: 0.75 55 is 76 19 66 14.8 2 is .7 2 Dosage Unit: mcj/kg/clay 1.3 1.2 1.2 .07 2 Dosage 1.3 1.6 S.s 4.7 8.6 4.9 8.6 .07 2 4.8 .14 2 Unit: mg/kg/day 9.0 5.2 9.4 5.0 2.4 .21 2 8.7 .42 2 S.1 .14 2 Dosage Unit: mg/kg/day 1.2 8.2 4.i 1.7 8.9 5.0 1.4 .3S 2 9.6 .49 2 4.7 .42 2 3.8 3.7 3.8 .07 2 3.8 3.4 3.6 .28 2 3.8 3.9 3.8 .07 2 .8 .0 .4 .57 2 1.2 .2 .7 .71 2 .6 .2 .4 .28 2 5 109 6 ise 6 134 .7 34.6 2 2 8 209 6 117 7 .163 1.4 65.1 2 2 6 137 9 136 8 136 2.1 .7 2 2 A14INAL NUMBER ------ Group: I 105520 105526 MEAII s.D. Group: 3 rossos iOS523 MEAN S.D. N Group: 4 105511 105522 MEAN S.D. N APPENDIX 4 Individual clinical chemistry Data males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULPONIC POTASSIUM SALT (PFOS; T-62951 IN CYNOMOLCUS ACID AST/SGOT IU/L -------- ALT/SCPT IU/L -------- AIX PHOS IU/L -------- GOT IU/L -------- SDH IU/L -------- cx IU/L -------- ANYLASE IU/L -------- LIPASE IU/L -------- P A] U/ ---- Dose Level: 0 34 34 42 43 38 5.7 2 38 6.4 2 Dose Level: 0.15 60 63 46 73 53 9.9 2 68 7.1 2 Dose Level: 0.75 76 59 46 92 61 21.2 2 23.3 2 Dosage Unit: rno/kg/day 499 so 3 1046 199 5 772 124 4 386.8 105.4 1.4 2 2 2 Dosage Unit: mg/kg/day 99S 189 6 770 92 6 882 140 6 159.1 68.6 .0 2 2 2 Dosage Unit; mg/kg/day 844 156 3 573 158 1 708 lS7 2 191.6 1.4 1.4 2 2 2 960 1071 966 149.2 2 sis 624 570 77.1 2 787 1308 1048 368.4 2 512 462 487 35.4 2 1618 976 1297 454.0 2 727 523 625 144.2 2 90 98 94 S.7 2 871 549 710 227.7 2 36 2S 30 7.8 2 APPENDIX 4 individual Clinical Chemistry Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT IPFOS; T-629S) IN CYNOMOLGUS AftlKAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L ---- --- x CL MMOL/L tIMOL/L -------- -------- Group.- I IOSS20 105S26 I.IEAll S.D. N Group: 3 105505 105523 MEAN S.D. li Group- 4 105512 105522 MEAN S.D. N Dose Level: 0 10.1 5.0 10.8 S.9 10.4 .49 2 5.4 .57 2 Dose Level: 0.15 11.6 10.3 6.3 5.,4 11.0 .92 2 5.8 .64 2 Dose Level: 0.75 9.9 5.0 11.2 6.6 10.6 .92 2 5.8 1.13 2 Dosage unit: mg/kg/day 148 4.9 107 153 S.1 106 ISO 3.5 2 5.0 .14 2 106 .7 2 Dosage Unit: mg/kg/day 154 5.1 104 154 5.0 108 154 .0 2 5.0 .07 2 106 2.8 2 Dosage Unit: mg/kg/day isi S.1 108 iss 5.6 108 lS4 4.9 2 5.4 .35 2 108 .0 2 ANIMAL NUMBER ------ Group: 1 IOSS29 105549 HEAII S.D. N Group: 3 ZOSS39 ZOSSS2 MEAN s.D. u Group- 4 105533 105542 MEAN S.D. N APPENDIX 4 individual Clinical Chemistry Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTAS91UN SALT IPFOS; T-629S) IN CYNOMOLGUS ACID GLU MG/DL -------- un MG/Dit -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA UNOL/L -------- CHOL MG/J[)L -------- TR MG/ ---- Dose Level: 0 Dosage Unit: mg!kg/day 44 16 1.4 8.4 4.4 4.0 .9 6 89 64 14 1.1 8.5 4.3 4.2 .1 13 148 S4 15 1.2 8.4 4.4 4.1 .5 J.0 Lis 14."L 1.4 .21 .07 .07 .14 .57 4.9 41.7 2 2 2 2 2 2 2 2 2 Dose Level: 0.15 Dosage Unit: mgfkg/day 69 27 1.4 8.2 3.8 4.4 .5 11 141 sa 28 1.2 9.3 4.0 5.3 S 6 154 64 28 1.3 8.8. 3.9 4.8 .5 7.8 .7 .14 .78 .14 .64 .00 2 2 2 2 2 2 2 8 148 3.S 9.2 2 2 Dose Level: 0.7S Dosage Unit: mo/kg/day 86 25 1.6 9.1 4.6 4.S .1 84 12 1.4 8.2 4.0 4.2 .0 a 139 s 119 85 18 1.5 8.7 4.3 4.4 .0 1.4 9.2 .14 .64 .42 .21 o7 2 2 2 2 2 2 2 6 129 2.1 14.1 2 2 ANIMAL NUMBER ------ Group: 1 IOSS29 105549 MEA14 S.D. N Group: 3 105539 IOSS52 MEAN S.1). N Group: 4 IOSS33 105542 MEAN S.D. N APPENDIX 4 individual Clinical Chemistry Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY wrTH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT IPFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT IU/L IU/L -------- -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- cx IU/L -------- AMYLASE ZU/L -------- LIPASE IU/L -------- p U/ ---- Dose Level: 0 66 97 46 77 56 14.1 2 87 14.1 2 Dose Level: O.lS 36 71 60 ss 49 17.0 2 78 9.9 2 Dose Level: 0.75 43 70 46 iss 44 2.1 2 112 60.1 2 Dosage Unit: mg/kg/day 143 82 2 169 39 5 156 60 4 18.4 30.4 2.1 2 2 2 Dosage Unit: mg/kg/day 114 67 4 205 79 9 160 73 6 64.3 B.S 3.5 2 2 2 Dosage Unit: mg/kg/day 250 ios 2 220 ss 1 235 so 2 21.2 3S.4 .7 2 2 2 1212 1024 1118 132.9 2 602 1513 1058 644.2 2 1471 659 1065 574.2 2 390 342 366 33.9 2 386 722 S54 237.6 2 448 4SO 449 1.4 2 0 0 0 .0 2 63 83 73 14.1 2 33 94 64 43.1 2 APPENDIX 4 individual Clinical Chemistry Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT IPFOS; T-6295) IN CYNOMOLCUS ANIMAL IIUHBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L ---- --- K MMOL/L ------- CL MMOL/L -------- Group. 1 105529 105549 HEAII S.D. it Group: 3 105539 iU55S2 MEAN S.D. u Group: 4 iOSS33 105542 MEAN S.D. N Dose Level: 0 9.8 5.0 9.6 4.4 9.7 .14 2 4.7 .42 2 Dose Level: O.lS 9.4 4.8 10.2 S.S 9.8 S7 2 5.2 .49 2 Dose Level: 0.75 10.3 4.4 10.3 4.1 10.3 .00 2 4.2 .21 2 Dosage Unit: mg/ka/day 146 5.1 100 148 4.8 107 147 1.4 2 5.0 .21 2 104 4.9 2 Dosage Unit: mg/ky/day 148 5.2 107 iS4 S.1 109 isi 4.2 2 5.2 .07 2. 108 1.4 2 Dosage Unit: mg/ka/day 154 5.2 109 is$ 5.8 ill 156 2.8 2 5.5 .42 2 110 1.4 2 ANIMAL NUMBER ------ Group: 1 105520 105526 MEAN S.D. N Group; 3 105505 105523 MEAN S.D. N Group: 4 105511 105522 MEAN S.D. N "PENDIX 4 individual clinical Chemistry Data Hales Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLCUS GLU UN CRFAT T PRO ALD GLOB T BILI SBA MG/DL -------- MG/DL -------- MG/DL -------- C/DL -------- G/DL -------- G/DL -------- MG/DL -------- UNOL/L -------- CHOL TR MG/DL MG/ ------- ---- Dose-Level: 0 74 17 71 24 72 2.1 2 20 4.9 2 Dose Level: 0.15 73 23 76 28 74 2.1 2 26 3.S 2 Done Level: 0.7S 63 19 76 17 70 9.2 2 is 1.4 2 Dosage Unit: mg/kg/day 1.3 8.9 S.o 1.3 8.9 5.3 1.3 .00 2 8.9 .00 2 5.2 .21 2 Dosage Unit. mg/kg/day 1.2 9.0 5.4 1.1 8.1 4.9 1.2 .07 2 8.6 .64 2 5.2 .35 2 Dosage Unit: mg/kg/day 1.1 8.3 4.5 1.3 8.5 5.0 1.2 .14 2 8.4 .14 2 4.8 .35 2 3.9 3.6 3.8 .21 2 3.6 3.2 3.4 .28 2 3.8 3.5 3.6 .21 2 .7 .3 .5 .28 2 1.1 .5 .8 .42 2 .6 .3 .4 .21 2 5 los 6 148 6 126 .7 30.4 2 2 7 206 6 127 6 166 .7 55.9 2 2 6 116 3 222 4 119 2.1 4.2 2 2 ANIMAL NUMBER ------ Group: I 105520 105526 MEAN S.D. Group: 3 .Tos5os 105523 HEM S.D. Group: 4 105511 105522 MEAN S.D. N APPENDIX 4 individual clinical chemistry Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOWIC ACID POTASSIUM SALT (PFOS: T-62951 IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS GGT SDH cx IU/L IU/L IU/L IU/L IU/L IU/L -------- -------- -------- -------- -------- ------- AMYLASE LIPASE p A] IU/L rU/L U/ -------- -------- ---- Dose Level: 0 46 45 53 38 so 4.9 2 42 4.9 2 Dose Level: 0.15 64 63 55 70 60 6.4 2 66 4.9 2 Dose Level: 0.75 62 48 58 84 60 2.8 2 66 25.5 2 Dosage Unit: mg/kg/day 387 53 3 1040 222 8 '714 138 6 461.7 119.S 3.S 2 2 2 Dosage Unit: mg/kg/day 91s 188 9 725 98 a 820 143 a 134.4 63.6 .7 2 2 2 Dosage Unit: mg/kg/day 765 154 6 479 156 2 622 155 4 202.2 1.4 2.8 2 2 2 2123 2151 2137 19.8 2 1243 1747 1495 356.4 2 617 2004 1310 980.8 2 388 363 376 17.7 2 1640 948 1294 489.3 2 616 415 516 142.1 2 38 37 38 7 2 793 365 579 302.6 2 35 31 33 2.8 2 APPENDIX 4 Individual Clinical Chemistry Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ------ CA MG/DL__ ------ I PHOS _MG/DL__ ----- NA _MNOL/L ------- K IAMOL!L -------- CL MMOL/L -------- Group: I ZOSS20 105526 MEAN s.D. N Group: 3 105505 105523 MEAN S.D. N Group: 4 iossii IOSS22 MEAN S.D. N Dose Level: 0 10.3 4.2 11.0 5.2 10.6 .49 2 4.7 .71 2 Dose Level: 0.15 11.9 5.7 9.9 S.S 10.9 1.41 2 S.6 14 2 Dose Level: 0.75 10.2 5.2 10.9 4.6 10.6 .49 2 4.9 .42 2 Dosage Unit: mg!kg/day 154 5.3 111 IS7 5.5 ill 156 2.1 2 5.4 .14 2 ill .0 2 Dosage 160 iso Unit: mg/kg/day 5.8 113 S.1 109 iss 7.1 2 S.4 .49 2 ill 2.8 2 Dosage 153 1SG Unit: mg/kg/day 5.9 113 5.0 108 IS4 2.1 2 5.4 .64 2 110 3.5 2 ANIMAL NUMBER ------ Group: I 105529 105S49 MEAN S.D. Group: 3 105539 IOS552 MPAN S.D. N Croup: 4 105533 IOSS42 MEAN S.D. N APPENDIX 4 Individual Clinical Chemistry Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUORDOCTAME SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOTIOLGUS CLU UN CREAT MG/DL MG/DL MG/DL -------- -------- -------- T PRO G/DL -------- ALB C/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA UMOL/L -------- CHOL MGIDL -------- TRI MG/D ----- Dose Level: 0 54 21 56 le 55 1.4 2 20 2.1 2 Dose Level. 0.15 66 22 so 26 73 9.9 2 24 2.8 2 Dose Level: 0.7S 91 21 95 25 Dosage Unit: mg/kg/day .9 8.9 4.7 1.1 9.0 4.7 1.0 .14 2 9.0 o7 2 4.7 .00 2 Dosaqe Unit- mg/kg/day 1.1 8.3 3.8 1.0 9.1 4.0 1.0 .07 2 8.7 S7 2 3.9 .14. 2 Dosage Unit: mg/ka/day 1.2 9.2 4.9 1.1 8.1 4.0 4.2 4.3 4.2 .07 2 4.5 5.1 4.8 .42 2 4.3 4.1 1.1 .4 .8 .49 2 .8 .7 .9 .07 2 .3 .4 5 112 6 '162 6 137 .7 35.4 2 2 6 136 6 138 6 137 .0 1.4 2 2 13 IS2 5 131 as 23 1.2 8.7 4.4 4.2 .4 4.2 2.8 .07 .78 .64 .14 .07 2 2 2 2 2 2 2 9 142 5.7 14.8 2 2 ANIMA@L NUMBER ------ Group: 1 105529 ZOSS49 MEAN S.D. N Group: 3 105539 105552 MEAN S.D. N Group: 4 105533 TOSS42 MEAN S.D. N APPENDIX 4 individual clinical Chemistry Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULPONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLCUS ACID AST/SGOT ALT/SGPT IU/L IU/L -------- -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CR IU/L -------- ANYLASE IU/L -------- LIPASE IU/L -------- PA U/ ---- Dose Level: 0 110 297 61 106 86 34.6 2 202 135.1 2 Dose Level: 0.15 37 61 62 9s so 17.7 2 78 24.0 2 Dose Level: 0.75 67 78 45 83 56 15.6 2 so 3.5 2 Dosage Unit: mg/kg/day 157 109 7 167 4S 5 162 77 6 7.1 45.3 1.4 2 2 2 Dosage Unit: mg/kg/day 109 78 8 188 go is 148 55.9 2 79 1.4 2 12 4.9 2 Dosage Unit: mg/kg/day 243 117 5 213 56 3 228 86 4 21.2 43.1 1.4 2 2 2 2978 1838 2408 806.1 2 733 1009 871 195.2 2 2353 1241 1797 786.3 2 459 338 398 85.6 2 304 630 467 230.5 2 527 431 479 67.9 2 33 0 16 23.3 2 42 52 47 7.1 2 47 47 47 .0 2 APPENDIX 4 Individual Clinical Chemistry Data Females Day 364 26-wEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNO14OLCUS ANIMAL NUMBER ------ CA NG/DL ------ - I PHOS NA K CL MG/DL MMOL/L MMOL/L MMOL/L -------- -------- -------- -------- Group: 1 105529 105549 MEAN S.D. N Group: 3 105539 IOSSS2 MEAN S.D. N Group: 4 ZOSS33 105542 MEAN Doz.* Level: 0 9,7 5.6 10.1 4.2 9.9 .28 2 4.9 .99 2 Doze Level: 0.15 9.0 4.8 9.9 4.7 9.4 .64 2 4.8 .07 2 Dose Level: 0.75 io.s 4.6 10.0 4.3 10.2 .35 2 4.4 .21 2 Dosage Unit: mg/kg/day 144 4.3 103 151 5.6 109 148 4.9 2 S.0 .92 2 106 4.2 2 Dosage Unit: mg/kg/day 146 4.9 los 151 5.9 ill 148 3.5 2 5.4 .71 2 110 2.1 2 Dosage Unit: mg/kg/day IS3 5.3 ill 157 5.6 113 iss 2.8 2 S.4 .21 2 112 1.4 2 ANIMAL NUMBER Group: 1 IOSS20 IOSS26 MEAN S.D. Group.- 3 105505 105523 ME" S.D. N Group: 4 iossil 105522 MEAN S.D. N APPENDIX 4 Individual clinical chemistry Data Males Day 456 GLU KC/DL 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS Ulf 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 so 12 1.2 8.9 5.2 3.7 .8 68 16 1.2 8.5 4.9 3.6 .3 74 14 1.2 8.7 S.o 3.6 .6 8.5 2.8 ou 28 .21 .07 .35 2 2 2 2 2 2 2 I)ose Level: O.lS Dosage Unit: mg/kg/day es is 1.2 9.3 5.4 3.9 .6 94 111 1.1 9.9 5.5 3.4 .3 91 16 1.2 9.1 5.4 3.6 .4 4.2 1.4 .07 .28 .07 .35 .21 2 2 2 2 2 2 2 Dose Level: 0.75 Dosage Unit: mg/ka/day 64 13 1.0 S.s 4.S 4.0 .8 75 14 1.3 9.3 5.4 3.9 .3 70 14 1.2 8.9 S.0 4.0 .6 7.8 .7 .21 .57 .64 .07 .35 2 2 2 2 2 2 2 3 122 3 142 3 132 .0 14.1 2 2 5 216 6 139 6 179 .7 54-4 2 2 4 3 4 .7 2 122 114 118 S.7 2 ANIMAL NUMBER ------ Group: I 105520 105526 MEJU4 S.D. N Group: 3 iossos 105523 MEAN S.D. Group: 4. 105511 IOSS22 MEAN S.D. N APPENDIX 4 Individual Clinical Chemistry Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAHE SULPONIC ACID POTASSIUM SALT (PPOS; T-6295) IN CYNO14OLGUS AST/SCOT IU/ii -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMY"SF- IU/L -------- LIPASE IU/L -------- p U/ ---- Dose Level: 0 Dosage Unit: my/kglday 29 21 394 S9 2 77 319 11 29 26 @847 189 10 126 276 21 24 7.1.2 24 3.5 2 Dose Level: O.IS 620 124 6 32(1.3 91.9 S.7 2 2 2 Dosage Unit: mo/ko/day 102 34.6 2 298 30.4 2 16 7.1 2 29 46 21 45 2S 5.7 2 46 .7 2 Dose Level: 0.75 971 198 771 101 871 14.t.4 2 iso 68.6 2 Dosage Unit-. mg/kg/day 2 1 2 .7 2 163 119 141 31.1 2 413 487 450 S2.3 2 14 17 16 2.1 2 37 30 34 4.9 32 so 41 12.7 2 458 379 418 S5.9 2 129 148 138 13.4 2 1 179 0 225 0 202 .7 32.S 2 2 480 364 422 82.0 2 20 13 16 4.9 2 APPENDIX 4 Individual Clinical Chemistry Data Males Day 4S6 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS: T-629S) IN CYNOMOLGUs ANIMAL NUMBER ------ CA MG/DL -------- I PROS MG/DL -------- IIA I.IMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: I Dose Level: 0 Dosage Unit: mg/kg/day IOSS20 IOS526 HEAII S.D. n Group: 3 105505 105523 MEAN S.D. 11 Group: 4 105511 105522 MEM S.D. 10.4 S.7 10.1 6.4 10.2 .21 2 6.0 .49 2 Dose Level: 0.15 12.6 6.6 10.9 7.2 11.8 1.20 2 6.9 .42 2 Dose Level: 0.15 10.0 3.9 11.1 6.7 10.6 .78 2 5.3 1.98 2 156 5.7 113 ISO 5.1 109 153 4.2 2 5.4 .42 2 ill 2.8 2 Dosage Unit: mg/kg/day 167 6.3 lie 161 5.6 113 164 4.2 2 6.0 .49 2 116 3.S 2 Dosage Unit-. mg/kg/day 152 4.6 113 1SB S.4 109 iss 4.2 2 S.0 S7 2 III 2.8 2 ANIMAL NUMBER Group: I 105529 zOSS49 MEAN S.D. N Group: 3 IOS539 losss2 MEAN S.D. Croup- 4 ZOSS33 IOSS42 MEAN S.D. N APPENDIX 4 Individual clinical Chemistry Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PEWLUOROOCTAKE SULFOUIC POTASSIUM SALT (PFOS; T-62951 IN CYNOMOLCUS ACID (;Lu MG/DL ull NCIDL -------- CREAT NOJDL -------- T PRO C/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA UMOL/L -------- CHOL MG/DL -------- TR NGI ---- E@ose Level: 0 Dosage Unit: mglkg/day 48 17 79 17 64 21.9 2 17 .0 2 Doze Level: 0.15 79 16 78 is 78 .7 2 17 1 @4 2 Dose Level: 0.75 98 17 101 21 loo 2.1 2 19 2.8 2 .9 8.3 4.6 1.0 8.7 4.6 1.0 .07 2 O.s .28 2 4.6 .00 2 Dosage Unit: mo/ko/day 1.0 8.4 4.1 .9 9.0 4.1 1.0 .07 2 8.7 .42 2 4.1 .00 2 Dosage Unit: mg/kg/day 1.1 9.1 4.9 1.0 8.2 4.1 1.0 .07 2 8.7 .64 2 4.5 S7 2 3.7 4.1 3.9 .28 2 4.3 4.9 4.6 .42 2 4.2 4.1 4.2 .07 2 1.0 .3 .6 .49 2 .6 .5 .6 o? 2 .2 .3 .2 .07 2 7 99 4 142 6 120 2.1 30.4 2 2 4 144 6 144 s 144 1.4 .0 2 2 5 137 3 139 4 138 1.4 1.4 2 2 ANIKAL NUMBER Group: I IOSS29 105549 HEAR4 Groxip: 3 105539 105552 MEAti S.D. N Grc)-up: 4 105533 105542 MEAN G.ID. N APPENDIX 4 Individual Clinical Chemistry Data Females Day 456 26-wEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/Sr.OT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- CGT IU/L -------- St)" IU/L' -------- CR IU/L -------- ANYLASE LIPASE IU/L IU/L -------- -------- P AN U/L Dose Level: 0 Dosage Unit: mg/kg/day 56 183 139 96 30 as 174 49 6 200 293 9 3 244 244 12 43 18.4 2 134 69.3 2 Dose Level: 0.15 156 72 4 24.7 33.2 2.1 2 2 2 Dosage Unit: mg/kg/day 222 31.1 2 268 34.6 2 10 2.1 2 Dose 25 34 40 66 32 10.6 2 so 22.6 2 Level: 0.75 94 76 4 186 81 10 140 78 65.1 3.5 4.2 2 2 2 Dosage Unit: mg/kg/day 112 2S4 183 100.4 2 242 436 339 137.2 2 is 11 13 2.8 2 2S 25 25 .0 2 64 43 54 14.8 2 248 216 232 22.6 2 124 63 94 43.1 2 0 134 360 3 114 233 2 1 24 296 2.1 14.1 89.8 2 2 2 13 23 is 7.1 2 APPENDIX 4 Individual Clinical chemistry Data Females Day 456 26-WEEK CAPSULE TOXICITY sTuDy witli PERFLUOROOCTANE SULFONIC POTASSIUM SALT IPFOS: T-629S) IN cyriomoLGus ACID ANIMAL NUMBER ------ CA MG/DL -------- I PHOS 14G/DL -------- NA MIOL/L -------- K MMOL/L -------- CL tiMOL/L -------- Group: I lo5s29 IOSS49 14EAII S.D. 11 Group- 3 IOSS39 105552 MEAN S.D. 13 Group: 4 IOSS33 roSS42 MEAN S.D. N Dose Level: 0 9.6 4.9 10.2 S.4 9.9 .42 2 5.2 .35 2 I)ose Level: 0.15 9.5 S.3 10.1 5.0 9.8 .42 2 S.2 .21 2 Dose Level: 0.75 10.3 5.1 10.S 5.6 10.4 .14 2 5.4 .3s 2 Dosage Unit: mg/kglday 144 4.9 105 IS2 5.1 110 148 5.7 2 5.0 .14 2 ios 3.S 2 Dosage Unit: mg!kg/day lsi 5.4 153 S.9 ill 112 152 1.4 2 S.6 .3S 2 112 .7 2 Dozago Unit. mg/kglday iss 5.6 154 6.8 114 Ila 154 .7 2 6.2 .85 2 116 2.8 2 AN114AL NUMBER Group: I 105520 105526 MEAN S.D. Group: 3 IDS50S ZOSS23 HE" S.D. N Group- 4 iossii IOSS22 MEAN S.D. m APPENDIX 4 individual Clinical Chemistry Data Males Day S46 26-WEEX CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT IFFOS; T-629S) in CYNOMOLOUS GLU MGIDL UN MG/DL -------- CREAT MG/DL -------- T PRO O/DL -------- ALB C/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA UNOL/L -------- CHOL Ma/DL -------- TR lfc/ ----- Doze Level.- 0 Dosage Unitt mg/kg/day 79 14 1.2 8.17 4.6 4.1 S 86 18 1.3 8.9 4.e 4.1 .2 6 119 5 iso 82 16 1.2 8.8 4.7 4.1 .4 4.9 2.8 .07 .14 .14 .00 .21 2 .2 2 2 2 2 2 6 134 .7 21.9 2 2 Dose Level: 0.15 Dosage Unit: my/ka/day 77 29 1.2 8.6 4.9 3.7 .6 81 19 1.1 9.0 5.3 3.7 .3 5 200 3 132 79 19 1.2 8.8 5.1 3. *7 .4 2.8 .0 o7 .28 .20 .00 .21 2 2 2 2 2 2 2 Dose Level- 0.7S Dosage Unit: mg/kg/day 4 166 1.4 48.1 2 2 75 16 1.4 9.S 5.0 4.5 a3 16 1.4 9.3 5.2 4.1 .8 4 145 .3 10 132 79 16 1.4 9.4 5.1 4.3 .6 5.7 .0 .00 .14 .14 .28 .35 2 2 2 2 2 2 2, 7 138 4.2 9.2 2 2 ANlt4AL NUMBER Group: I IOSS20 105526 REA]ti S.D. Group: 3 iossos 105523 MEAN S.D. N Group- 4 rossii IOSS22 HE" S.D. APPENDIX 4 Individual Clinical Chemistry Data Males Day S46 26-WEEK CAPSULE TOXICITY S"MDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLCUS ACID ASTISGOT ALT/SGPT ALK PROS GGT SDH CK ANYLASS LIPASE PA IU/L I IU/L TU/L IU/L IU/L IU/L IU/L IU/L U/ -------- -------- -------- -------- -------- -------- -------- -------- ----- Dose Level: 0 Dosage Unit: mglkg/day 19 20 309 49 1 79 26S 10 28 30 701 183 19 144 259 17 24 6.4 2 25 7.1 2 Dose Level; 0.15 31 36 30 33 30 .7 2 34 2.1 2 Dose Level: 0.75 45 37 27 42 36 12.7 2 40 3.S 2 505 277.2 2 116 94.8 2 10 12.7 2 Dosage Unitz mg/kglday 846 178 1 662 93 s 754 136 3 130.1 60.1 2.8 2 2 2 Dosage Unit: mg/kg/day 467 149 0 342 147 0 404 98.4 2 148 1.4 2 0 .0 2 ill 46.7 2 130 212 171 58.0 2 165 165 165 .0 2 262 4.2 2 357 446 402 62.9 2 519 362 440 111.0 2 14 4.9 2 12 13 12 .7 2 22 11 16 7.8 2 APPENDIX 4 individual Clinical Chemistry Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAIIE SULFoNrc ACID POTASSIUM SALT IPFOS; T-629S) IN CYNOI-IOLGUS AtilKAL t4UMBER ------ CA HO/DL -------- I PHOS MG/DL -------- IIA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: I Z05520 IOSS26 14EAII S.D. Group: 3 105505 105523 MEAN S.D. N Group: 4 105511 105522 Dose Level: 0 10.8 6.S io.s 6.6 10.6 .21 2 6.6 .07 2 Dose Level: U.15 11.4 6.3 11.0 7.6 11.2 .28 2 7.0 .92 2 Dose Level: 0.75 12.0 5.4 11.8 6.2 Dosage Unit: nig.;kg/day 162 6.4 120 157 S.6 ill 160 3.5 2 6.0 .57 2 116 6.4 2 Dosage Unit: mg/kg!day 164 5.8 117 169 6.9 122 166 3.5 2 6.4 .78 2 120 3.5 2 Dosage Unit: mg/kglday 174 6.0 121 169 6.2 116 KEAN S.D. N 11.9 .14 2 5.8 .57 2 172 3.S 2 6.1 .14 2 118 3.5 2 ANIMAL NUMBER Group: I IDS529 105549 MEAN S.D. 11 Group: 3 105539 105552 MEAN S.D. Groul): 4 IOSS33 IOSS42 HEAR S.D. APPENDIX 4 Individual Clinical Chemistry Data Females Day S46 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOMANE SULPONIC ACID POTASSIUM SALT (PPOS; T-6295) III CYNOMOLCUS CLU M(;/DL uti MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SEA UNOL/L -------- CHOL HO/DL -------- TR NGI ---- Doze Level: 0 Dosacte Unit: mg/kg/day . 67 17 .9 8.2 4.4 3.9 .8 53 16 1.0 8.9 4.4 4.4 .3 60 16 L.0 8.5 4.4 4.1 .6 9.9 .7 .0-1 .42 .00 .42 .35 2 2 2 2 2 2 2 D4oso Level: 0.15 Dosage Unit: mg/kg/day 6 96 s 152 6 124 .7 39.6 2 2 71 19 1.1 8.5 3.9 4.6 .5 74 17 a 8.2 3.6 4.6 .6 72 18 I.o 8.4 3.8 4.6 .6 2.1 1.4 .21 .21 .21 .00 o? 2 2 2 2 2 2 2 Dose Level: 0.75 Dosage Unit: mg/kg/day 5 5 5 .0 2 147 129 138 12.7 2 100 19 1.2 9.0 4.6 4.4 .3 93 19 112 7.9 4.0 3.9 .3 96 19 1.2 8.4 4.3 4.2 .3 4.9 .0 .00 .78 .42 .35 .00 2 2 2 2 2 2 2 6 145 4 147 s 146 1.4 1.4 2 2 ANIMAL NUMBER ------ Group: I IOSS29 IOSS49 HEATI S.D. Group: 3 105539 IOSS52 MEAN S.D. N Group: 4 105533 105542 MEAN S.D. N APPENDIX 4 Individual clinical Chemistry Data Females Day 546 26-WF-EK CAPSULE TOXICITY STUDY WITH VERFLUottooCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-62951 IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS GGT SDH --I-U-/-L -- IU/L IU/L IU/L IU/L -------- -------- -------- ---- --- CK IU/L ANYLASE ZU/L LIPASE IU/L P AN U/L -------- -------- -------- ----- Dose Level: 0 53 191 30 49 42 16.3 2 120 100.4 2 Dose Level: 0.15 27 31 26 37 26 .7 2 34 4.2 2 Dose Level: 36 19 0.75 79 39 28 12.0 2 S9 28.3 2 Dosage Unit: mg/kg/'day 131 93 0 171 4S 0 151 69 0 28.3 33.9 .0 2 2 2 Dosage Unit: mg/kg/day 96 76 2 195 82 1 146 79 2 70.0 4.2 .7 2 2 2 Dosage Unit: mg/kg/day 240 117 3 186 61 0 213 89 2 38.2 39.6 2.1 2 2 2 216 93 154 87.0 2 80 109 94 20.5 2 164 97 130 47.4 2 316 245 280 SO.2 2 252 454 353 142.8 2 372 2so 311 86.3 2 11 12 12 .7 2 14 8 11 4.2 2 12 la is 4.2 2 APPENDIX 4 Individual clinical Chemistry Data Females Day 546 26-WEEK CAPSULE ToXiciTY STUDY WITH PERFLUOROOCTANE SULFONXC ACID POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ------ CA I PHOS MA K CL tIG/DL MGIDL MMOL/L MtIOL/L M14OL/L -------- -------- -------- -------- -------- Group: 1 105529 105549 MEAN S.D. Group: 3 IOSS39 ZOSS52 MEAN S.D. 11 Group: 4 105533 105S42 MEAN S.D. Dose Level: 0 10.1 5.2 10.1 S.6 1().i .f)lj 2 S.4 .28 2 Dose Level: 0.15 9.8 5.4 10.2 4.9 10.0 .28 2 5.2 .35 2 Dose Level: 0.75 10.3 5.9 10.7 5.4 10.5 .28 2 5.6 .35 2 Dosage Unit: mg,'kglday ISO S.i 108 152 5.3 ill LSI 1.4 2 S.2 .14 2 110 2.'1 2 Dosage Unit: mg!kg!day 155 5.4 112 157 6.1 117 156 1.4 2 S.8 .49 2 114 3.5 2 Dosage Unit: mg/kgtday 159 5.6 115 165 6.7 124 162 4.2 2 6.2 .78 2 120 6.4 2 Appendix 4 Individual Clinical Urinalysis Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NMER ------ U VOL SP GR u PH ML -------- -------- -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 37.0 20.0 47.0 75.0 32.0 30.0 1.025 1.032 1.025 1.018 1.030 1.023 41.5 17.76 6 1.026 .0050 6 Dose Levelt 0.03 8.0 7.0 8.0 7.5 7.5 6.0 7.3 .75 6 Dosage Unit: mg/kg/day 105514 105515 105516 105521 67.0 1.019 7.0 46.0 1.023 7.5 52.0 1.020 7.0 45.0 1.023 8.0 MEAN S.D. N Group: 3 105505 105510 iessis 105523 105524 105528 52.5 10.15 4 1.021 .0021 4 Dose Level: 0.15 228.0 52.0 93.0 43.0 46.0 125.0 1.007 1.025 1.020 1.026 1.025 1.013 7.4 .48 4 Dosage Unit: mg/kg/day 7.0 7.0 7.0 7.0 7.5 7.0 KEAN S.D. N 97.8 71.41 6 1.019 .0078 6 7.1 .20 6 637 Appendix 4 Individual Clinical Urinalysis Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS ANIMAL NUMBER ------ U VOL SP CR U PH ML -------- -------- -------- SULPONIC MONXRYS ACID Group.- 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Dose Level: 0.75 43.0 59.0 68.0 173.0 92.0 66.0 1.026 1.022 1.018 1.008 1.013 1.022 83.5 46.63 6 1.018 .0066 6 Dosage Unit: mg/kg/day 7.o 7.5 7.0 7.0 7.5 7.0 7.2 .26 6 638 Appendix 4 individual Clinical Urinalysis Data males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTARE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID ANIMAL NUMBER ------ u PRO U GLU U KET U BILI U BLOOD UROBILI MG/DL -------- -------- -------- -------- -------- -------- Group: 1 105508 105517 1()5519 105520 105526 105527 Group: 2 105514 105515 105516 105521 Group: 3 105505 105510 105518 105523 105524 105528 Group: 4 105506 105507 105509 105511 105512 105522 Dose Levels 0 0 10 0 0 10 + 0 Dose Level: 0.03 0 - 0 - 10 - 10 - Dose Level: 0.15 0 10 30 10 10 0 Dose 10 0 10 0 0 10 Levels - 0.7S Dosage Unit: mg/kg/day + ++ Dosage unit: mg/kg/day ++ + Dosage Unit: mg/kg/day ++ Dosage Unit.- mg/kg/day ++ + ++ + + 639 ANIMAL NMBER ------ Group: 1 lossoo 105517 105519 105520 105526 105527 Group: 2 105514 105515 105516 105521 Group: 3 105505 105510 105518 105523 105524 105528 Group.- 4 105506 105507 105509 105511 105512 105S22 Appendix 4 Individual Clinical urinalysis Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID RSC WEC EPITH BACT CASTS CRYSTALS CRYSTALS URINE C PER HPF PER HPP PER HPF PER HPF PER LPF PER LPFI PER LPF2 APPI -------- -------- -------- -------- -------- -------- -------- -------- Dose Level: 0 Dosage Unit: mg/kg/day 0 0 0 3 0 2B4D 0 vx 0 0 0 0 2 0 3 3 0 0 2B4D 0 DK PO 0 0 1 2 0 4B4B 0 484D 0 CL - BK - 0 0 1 2 0 483D 0 CK - 0 0. 0 1 0 483E 0 SK - Dose Level: 0.03 Dosage units mg/kg/day 0 0 1 3 0 4B29 0 CK - 0 0 0 3 0 4B4D 42 CL - 0 0 0 3 0 4B2D 0 cx - 0 0 0 3 0 4B4D 0 DL - Dose Level: 0.15 Dosage Unit; mg/kg/day 0 0 1 2 0 3B 0 BK - 0 0 0 3 0 4B4D 4z BL - 0 0 4 3 0 48 0 DL - 0 0 0 3 0 482D .0 BL - 0 0 0 3 0 3B4D 0 CK - 0 0 1 3 0 4B 0 BK - Dose Level: 0.75 Dosage Unit: mg/kg/day 2 0 1 3 0 2B2D 0 CK - 0 0 1 1 0 1 3 3 0 4B4D 0 CL Q 0 0 1 3 0 0 4BlE 0 4B 0 BK Q BK 0 0 1 3 0 2B 0 Q BK 0 1 1 2 0 2B 0 Bi 640 Appendix A Individual Clinical Urinalysis Data Females Day -27 26-wFzx CAPSULE TOXICITY STUDY WITH PERFLUOROOCTME POTASSIUM SALT (PFOS: T-6295) IN CYMONOLGUS ANIMAL NUMBER ------ u VOL KL -------- SP GR -------- u PH -------- SULF014rC ACID MONKEYS Group: 1 105529 105530 105531 105535 105544 105549 MEAN S.D. m Group: 2 105537 105541 105547 105550 Dose Level: 0 52.0 100.0 57.0 4S.0 240.0 50.0 1.017 1.020 1.020 1.023 1.007 1.023 90.7 75.84 6 1.018 .0060 6 Dose Level% 0.03 225.0 48.0 45.0 52.0 1.007 1.023 1.024 1.023 Dosage Units mg/kg/day 7.0 7.0 7.5 7.0 7.5 8.0 7.3 .41 6 Dosage Unit: mg/kg/day 7.5 7.0 7.0 7.0 MEAN S.D. N Groups 3 105532 105538 105539 105545 105548 105552 MEAN S.D. N 92.5 88.38 4 1.019 .0082 4 Dose Levels 0.15 140.0 61.0 53.0 .62.0 64.0 51.0 1.012 1.023 1.026 1.018 1.020 1.025 71.8 33.80 6 1.021 .0052 6 7.1 .25 4 Dosage Unit: mg/kg/day 9.0 7.5 8.0 7.0 8.0 8.0 7.8 .42 6 641 Appendix 4 individual Clinical Urinalysig Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOWOLGUS SULPONIC ACID MONKEYS ANIMAL NUMBER ------ U VOL ML -------- SP GR -------- U PH -------- Group- 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Dose Level: 35.0 59.0 64.0 247.0 72.0 51.0 88.0 78.91 6 0.75 1.026 1.024 1.023 1.007 1.019 1.021 1.020 .0068 6 t)osage Unit: mg/kg/daY 7.5 8.0 7.5 7.0 7.0 7.0 7.3 .41 6 642 Appendix 4 Individual Clinical Urinalysis Data Females Day -27 26-wp,Ex CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MON M S ANIMAL NUMBER ------ U PRO U GLU U KET U BILI U BLOOD UROBILI MG/DL -------- -------- -------- -------- -------- -------- Group.- 1 105529 105530 105531 105535 105544 105549 Dose Level: 0 0 - 10 - 0 - D - 0 - 0 - Dosage Units mg/kg/day ++ + ++ + Group: 2 Dose Level: 0.03 Dosage Unit: mg/kg/day 105537 0 - +++ 105541 0 - + 105547 10 - ++ 105550 0 - Group: 3 105532 105538 105539 105545 105548 105552 Dose Level: 0.15 0 - 0 - 10 - 0 - 0 - 0 - Dosage Units mg/kg/day + ++ ++ + Group- 4 105533 105534 105536 105540 105542 105551 Dose Level: 0.75 10 - 0 - 0 - 0 - 0 - 0 - Dosage Units mg/kg/day 643 ANIMAL NUMBER ------ Group% 1 105529 105530 105531 105535 105544 105549 Group: 2 105537 105541 105547 105550 Group: 3 105532 105539 105539 105545 105548 105552 Group: 4 105533 105534 105536 105540 105542 105551 Appendix 4 individual Clinical Urinalysis Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS: T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID RSC WBC EPITH BACT CASTS CRYSTALS CRYSTALS URINE PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 APP1 -------- -------- -------- -------- -------- -------- -------- -------- --- Dose Level: 0 Dosage Unit: mg/kg/day 0 1 1 3 1H 3B4D 0 BK 0 0 0 3 0 4B 0 DL 0 0 1 3 0 4B4D 0 CR 0 0 0 3 0 2B2D 0 CL 0 0 2 3 0 4B 0 AK 0 0 0- 1 0 4BID 19 BK Dose Level: 0.03 Dosage Unitt mo/kg/day 0 0 1 3 0 4B4D 0 BK 0 1 1 3 0 4B2D 0 DL 0 0 0 3 0 2B 0 DL 0 0 1 2 0 4BlE 0 CK Dose Level: 0.15 Dosage Unitt mg/kv/day 0 0 2 2 0 lD4F 0 ni 0 0 1 2 0 IBIN IF CK 0 0 1 3 0 4B 0 CK 0 0 1 2 0 4B 0 CK p 0 0 0 3 0 2B 0 CL 0 0 2 3 0 4B 0 CL Dose Level: 0.75 Dosage Unit: mgfkg/day 0 1 2 3 0 2B4D' 0 DK 0 0 1 2 0 AB4D 0 CL 0 0 1 3 0 3B3D 0 CL 0 0 4 3 0 0 0 AX 0 1 1 3 0 4BIR 0 CK 0 0 1 3 0 4BID 0 cx 6M Appendix 4 individual Clinical Urinalysis Data Males Day 37 26-WEEK CAPSULE TOXRCITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS; T-6295) In CYNOMOLOUS W)MKEYS ANIMAL NUMBER ------ U VOL SP GR U PH ML -------- -------- -------- Group: 1 105508 105517 105519 105520 105526 105527 tmm S.D. N Group; 2 IOSS14 105515 105516 105521 MEAN S.D. n Group: 3 105505 105510 105519 105523 105524 105528 TEEM S.D. N Dose Levelz 0 56.0 47.0 40.0 66.0 26.0 58.0 1.023 1.025 1.021 1.013 1.006 1.017 50.2 13.75 6 1.018 .0071 6 Done Level: 0.03 62.0 108.0 38.0 82.0 72.5 29.73 4 1.020 1.017 1.028 1.019 1.021 .0048 4 Dose Levelt 0.15 307.0 34.0 70.0 54.0 37.0 64.0 1.002 1.023 1.017 1.019 1.028 1.025 94.3 105.16 6 1.019 .0092 6 Dosage Unit- mg/kg/day 8.0 7.0 8.0 7.0 7.5 7.5 7.5 .45 6 Dosage Unit: mg/kgtday 7.0 7.5 8.0 7.5 7.5 .41 4 Dosage Uniti mg/kg/day 7.0 7.5 7.5 7.5 7.0 7.0 7.2 .27 6 645 Appendix A Individual Clinical UrinalySis Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLTIOROOCTAKE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ACID ANIMAL NUKBER ------ U VOL ML -------- SP GR -------- U PH -------- Groups 4 105506 105507 105509 105511 105512 105522 Dose Levels 0.75 50.0 52.0 36.0 110.0 146.0 80.0 1.023 1.026 1.023 1.008 1.007 1.018 Dosage Units mg/kg/day 8.0 8.0 8.0 6.5 7.0 6.5 MEAN S.D. N 79.0 42.12 6 1.018 .0082 6 7.3 .75 6 646 Appendix 4 individual Clinical Urinalysis Data males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ U PRO U GLU MG/DL -------- -------- U KET ------- U BILI --- U BLOOD UROBILI -------- Group: 1 Dose Levelt 0 Dosage unit: mg/kg/daY IOS508 0 - + 105517 0 - ++ 105519 0 - 105520 0 - 105526 0 - + 105527 0 - Group: 2 Dose Levelt 0.03 Dosage Unit: mg/kg/day iOS514 105515 105516 iG5521 Group: 3 105505 105510 105518 105523 105524 105528' Group: 4 105506 105507 iOS509 105511 105512 X05522 0 0 0 0 Dose Levelt 0.15 0 - 0 - 0 - 0 - 0 - 0 - Dose Level: 0.75 0 - 0 - 0 - 0 - 0 - 0 - Dosage Unit-. mg/kg /day + ++ Dosage Unit: mg/kg/day ++ + + (A7 Appendix 4 Individual Clinical Urinalysis Data males Day 37 ANIMAL NUMBER ------ Group: I 105508 105517 105519 105520 105526 105527 Groupt 2 105514 105515 105516 105521 Group: 3 105505 105510 105518 105523 105524 105528 Group: 4 105506 105507 105509 105511 105512 105522 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID RBC PER HPP -------- WBC PER HPF -------- EPITH PER HPP -------- BACT PER HPF -------- CASTS PER LPF -------- CRYSTALS PER LPF1 -------- CRYSTALS URINE COMMENTS PER LPF2 APP1 - ------ -------- -------- Dose Level: 0 Dosage unit- mg/kg/day 0 0 1 2 0 4D 0 0 0 1 2 2 0 0 ID 0 3E3F 0 0 0 0 0 0 1 1 0 0 0 00 00 0a 11 00 l4DBlD 00 Dose Level: 0.03 Dosage Unit: mg/kg/day 1 0 1 2 0 2B 0 0 0 0 3 2 0 0 4B4D 0 481D 0 0 0 1 2 0 4B2D 1H 0 0 0 Dose Level: 0.15 Dosage Unit: mg/kg/day 0 0 0 0 0 IB 0 0 0 a 3 0 4D 0 3D 0 0 0 0 1 1 2 0 0 2D3E 0 0 0 0 1 1 1 0 0 0 0 0 0 2 0 4BlE 0 Dose Level: 0.75 Dosage unit: mg/kg/day 0 0 1 2 0 0 0 0 3B4D 0 0 0 0 1 1 0 0 0 0 0 0 0 1 0 3 0 IR 0 0 0 0 3 0 2a 0 0 0 0 2 0 0 0 BK CK BK Bi p Di Di p BK PQ BK p CK BL AJ BK BK PQ BK Q CK BK BK p BK BK Di BJ BK pa 648 Appendix 4 Individual Clinical urinalysis Data . Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS POTASSIUM SALT (PFOS,; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ------ U VOL SP GR U PH ML -------- -------- -------- SULFONIC MONKEYS ACID Groupt 1 105529 105530 105531 105535 105544 105549 S.D. N Group. 2 105537 105541 105547 105550 MEAN S.D. N Groups 3 105532 105538 105539 105545 1009548 1 552 MEAN S.D. N Dose Level: 0 14.0 20.0 31.0 564.0 38.0 44.0 1.010 1.003 1.026 1.001 1.020 1.021 118.5 218.S3 6 1.014 .0103 6 Dose Level: 0.03 170.0 46.0 76.0 55.0 1.011 1.020 1.016 1.024 86.8 56.91 4 1.018 .0056 4 Dose Level: 0.15 78.0 186.0 66.0 85.0 47.0 40.0 83.7 53.OS 6 1.014 1.006 1.019 1.012 1.024 1.026 1.017 .0076 6 Dosage Unit. mg/kg/day 8.5 8.0 8.0 7.5 8.0 8.0 8.0 .32 6 Dosage Unit: mg/kg/day 7.5 8.0 9.0 7.5 7.8 .29 4 Dosage-Unit: mg/kg/day 7.5 7.5 7.0 7.5 8.0 7.5 7.5 .32 6 649 Appendix 4 individual Clinical UrinalysiS Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N U VOL SP GR U PH ML -------- -------- -------- Dose Levels 0.75 Dosage unit: mg/kg/day 38.0 1.024 8.0 32.0 1.026 8.5 44.0 1.020 8.0 417.0 1.003 8.0 34.0 1.025 7.0 36.0 1.026 7.0 100.2 155.27 6 1.022 .0094 6 7.8 .61 6 650 Appendix 4 individual Clinical Urinalysis Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ U PRO MG/DL ------- U GLU -------- U KET ------- U BILI --- ---- U BLOOD ------- UROBILI -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day 110055552390 010 -- -- ++ 105531 0 -- -- -+++ 105535 0 105544 0 - + 105549 0 - Group: 2 Dose Level: 0.03 Dosage uniti mg/kg/day 105537 0 - 105541 0 - + 105547 0 - 105550 0 - Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day 105532 0 105538 0 105539 0 - 105545 0 - 105548 0 - 105552 0 - Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day 105533 0 - + + 105534 10 - 105536 0 - 105540 0 - 105542 0 - 105551 0 - 651 ANIMAL NUMBER ------ Group-. I 105529 105530 105531 105535 IOSS44 105549 Group. 2 105537 105541 105547 105550 Group: 3 105532 105538 105539 105545 105548 105552 Group-. 4 105533 105534 105536 105540 105542 105551 Appendix 4 Individual Clinical Urinalysis Data Females Day 37 26-WEEK CAPSULE ToxiciTy STUDY WITH PERFLUOROOCTME POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SUMMIC MONKEYS ACID RSC PER HPF -------- WBC PER HPF -------- EPITH PER EPP -------- 8ACT PER HPF -------- CASTS PER LPF -------- CRYSTALS PER LPP1 -------- CRYSTALS PER LPP2 -------- URINE APP1 -------- COMMENTS -------- Dose Level: 0 Dosage Unit, mg/kg/day 0 0 2 1 0 lE2F 0 0 0 0 3 0 4B 0 0 1 0 2 0 3B4D 0 0 0 1 1 0 0 0 0 0 0 2 0 383D 0 0 1 0 3 0 lElF 0 Dose Level: 0.03 Dosage Unit: mg/kg/day BJ p BLW CL - AK - BK - BK - 0 0 1 2 0 4B 0 0 0 1 2 0 4B4D 0 0 0 0 1 0 2D 0 0 0 0 1 0 1B 0 Dose Leveli 0.15 Dosage Unit: mg/kg/day BK - BK - BK p SK 0 i 1 2 0 4B2E 0 BK 0 0 0 0 2 0 1 0 3B 0 SK 0 0 1 3 3 0 0 4B3E 0 4B4D 0 ax - BL 0 0 0 3 0 3BlD 0 BK 0 0 1 1 0 .3BID 1H DL Dose Level: 0.75 Dosage Unit: mg/kg/day 0 1 1 3 0 3B3D IE BK 00 00 10 11 00 24BB4lDD 03B BBKL p 00 01 11 21 00 03D 00 ABKX p 0 1 1 2 0 4BlD 0 BK 652 Appendix 4 individual Clinical Urinalysis Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOHOLGUS SULPONIC MONKEYS ACID ANIMAL NU14BER ------ U VOL ML -------- SP GR -------- U PH -------- Group- I 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 KEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 MEAN S.D. N Dose Level: 0 40.0 67.0 54.0 65.0 179.0 60.0 1.025 1.017 1.017 1.014 1.010 1.022 77.5 50.66 6 1.018 .0054 6 Dose Levels 0.03 44.0 69.0 28.0 108.0 1.010 1.020 1.028 1.016 62.2 34.86 4 1.018 .0076 4 Dose Level: 0.15 192.0 53.0 82.0 131.0 25.0 84.0 1.006 1.021 1.014 1.006 1.031 1.011 94.5 59.43 6 1.015 .0095 6 Dosage unit: mg/kg/day 8.0 8.0 8.0 7.5 8.0 8.5 8.0 .32 6 Dosage Unit: mg/kg/day 8.5 8.0 7.5 8.0 8.0 .41 4 Dosage unit: mg/kg/day 8.0 8.0 8.0 7.5 8.0 7.0 7.8 .42 6 653 Appendix 4 individual Clinical urinalysis Data males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFOt4lC ACID MONKEYS ANIMAL NUMBER ------ Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N U VOL ML -------- SP GR -------- U PH -------- Dose Level: 50.0 66.0 34.0 107.0 89.0 62.0 0.75 1.020 1.019 1.023 1.009 1.013 1.019 Dosage Unit: mg/kg/daY 7.5 8.0 8.0 8.0 7.5 8.5 68.0 26.39 6 1.017 .0051 6 7.9 .38 6 654 Appendix t individual Clinical urinalysis Data males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ANIMAL NUMBER ------ U PRO U GLU MG/DL -------- -------- U KET ------- U BILI U BLOOD -------- ------ - UROBILI -------- Group: 1 Dose Levelt 0 Dosage Unit: mg/kg/day 105508 105517 105519 105520 105526 105527 Group: 2 10 10 - 0 - 0 - 0 - 10 - Dose Level: 0.03 ++ + + Dosage Unit: mg/kg/day 105514 105515 105516 105521 Group: 3 0 - 10 - 10 - 0 - Dose Level: 0.15 ++ ++ Dosage Unit: mg/kg/day 105505 0 - 105510 0 - 105518 0 - 105523 0 - + 105524 10 - 105528 0 - + Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day 105506 10 - 105507 10 - 105509 10 - 105511 0 - 105512 0 - 105522 10 - 655 ANIMAL NUMBER ------ Group: 1 105508 105517 105519 105520 105526 105527 Group: 2 105514 105515 105516 105521 Group: 3 105505 105510 105518 105523 105524 105528 Group: 4 105506 iO5507 105509 105511 105512 105522 Appendix 4 individual Clinical urinalysis Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFCNIC MONKEYS ACID RBC WBC PER HPF PER HPF -------- -------- EPITH BACT PER HPF PER HPF -------- -------- CASTS CRYSTALS CRYSTALS PER LPF PER LPF1 PER LPF2 -------- -------- -------- URINE APP1 -------- COMMENT ------- Dose Level: 0 Dosage unit: mg/kg/day 0 0 0 3 0 2B3D 0 0 1 1 2 0 2B2D 0 0 0 1 1 0 28 0 0 0 1 2 0 2B3D 0 0 0 1 2 0 2B 0 0 0 1 3 0 2B4D 0 Dose Level: 0.03 Dosage unit: mg/kg/day 0 0 1 2 0 2BlE 0 0 0 1 32 00 24DB4D 00 0 0 1 0 0 0 3 0 3BlD 0 i)ose Level: O.i5 Dosage Unit: mg/kg/day 0 1 0 3 0 4BlD 0 0 0 0 1 0 3B&D 1E 0 0 1 3 0 4B3D 0 0 1 1 2 0 2B 0 0 0 1 2 0 2B4D 0 0 0 1 2 0 3BlB 0 Dose Level: 0.75 Dosage unit: mg/kg/day 0 0 1 1 0 4D 0 0 0 1 2 0 4D 0 0 1 1 1 0 0 0 0 0 1 1 0 2BID 0 0 0 1 2 0 1D 0 0 1 0 3 0 lB3D 0 CK Q CK - CK - BK - BJ - CK - AJ CK CK p BK AK CK BK AK cx p EK p CK CK PO CK p BK Q Bi BK 656 Appendix 4 individual Clinical urinalysis Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS NOMMS ANIMAL NUMBER ------ Group: 1 105529 105530 105531 105535 IOSS44 IOSS49 U VOL SP GR U PH ML -------- -------- -------- Dose Level: 0 Dosage unit: mg/kg/day 62.0 1.020 8.0 68.0 1.022 8.5 31.0 1.024 8.0 195.0 1.005 8.0 60.0 1.016 8.0 30.0 1.026 8.5 MEAN S.D. N Group- 2 74.3 61.32 6 1.019 .0076 6 Dose Level: 0.03 8.2 .26 6 Dosage Unit: mg/kg/day 105537 105541 105547 105550 tmm S.D. N Group: 3 97.0 18.0 50.0 49.0 1.015 1.028 1.018 1.021 53.5 32.58 4 1.020 .0056 4 Dose Level: 0.15 8.0 8.0 7.5 7.0 7.6 .48 4 Dosage unit: mg/kg/day 105532 105538 105539 105545 105548 105552 98.0 1.010 7.5 56.0 1.022 8.0 47.0 1.022 8.0 98.0 1.016 8.0 30.0 1.028 7.5 45.0 1.020 8.0 MEAN S.D. N 62.3 28.86 6 1.020 .0061 6 7.8 .26 6 657 Appendix 4 Individual Clinical Urinalysis Data Females Day 62 26-WEEK.CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNO14OLGUS MONKEYS ACID ANIMAL NUMBER ------ Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N U VOL ML -------- SP GR -------- U PH -------- Dose Levelt 0.75 Dosage unit: mg/kg/day 45.0 1.020 7.5 115.0 1.011 8.0 42.0 1.024 7.5 158.0 1.010 8.0 99.0 1.007 7.5 27.0 1.030 7.0 61.0 51.27 6 1.017 .0091 6 7.6 .38 6 658 Appendix 4 individual Clinical Urinalysis Data Females DaY 62 26-WEEK ANIMAL NUMBER -----Group: 1 CAPSULE TOXICITY STUDY WITH POTASSIUM SALT (PFOS; T-6295) U PRO MG/DL ------- U GLU U KET pERpLUOROC)CTANE SULFONIC IN CYNOMOLGUS MONKEYS ACID U BILI U BLOOD UROBILI Does Level: 0 Dosage unit: mg/kg/day 105529 10 105530 10 105531 0 - + 105535 0 - 105544 0 - ++ 1055&9 10 - Group: 2 Doze Levels 0.03 Dosage Unit-. mg/kg/day 105537 10 - 105541 10 - 105'547 10 - 105550 10 - Group- 3 Doze Level: 0.15 Dosage Unit: mg/kg/day IOS532 10 - + 105538 10 - 105539 10 - 105545 0 - 105548 10 - 105552 10 - Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day 105533 10 - + 105534 0 - 105536 10 - 105540 0 - 105542 0 - 105551 10 - 659 Appendix A Individual Clinical Urinalysig Data Females Day 62 ANIMAL NUMBER ------ Group: 105529 105530 105531 105535 105544 105549 Group: 2 105537 105541 105547 105550 Group: 3 105532 105538 105539 105545 105548 105552 Group: 4 105533 105534 105536 105540 IOSS42 105551 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID RBC WBC PER HPF PER HPF -------- -------- SPITH PER HPF -------- BACT PER HPF -------- CASTS CRYSTALS PER LPF PER LPF1 --------- -------- CRYSTALS PER LPF2 -------- URINE APPI --- ---- COMMENTS -------- Dose Level: 0 Dosage Unit: mg/kg/day 0 0 1 2 0 0 4D 0 4B 0 1 0 1 3 2 0 2B3D 0 00 10 111 21 00 04DlE 00 2BID 0 0 0 0 0 1 3 0 Dose Level: 0.03 Dosage unit: mg/kg/day 0 0 1 2 0 2B4D 0 4B4D 0 0 1 1 3 0 4B2D 0 0 1 1 1 1 0 0 2D 0 0 1 2 CR p CK cx BJ p BK CK p CK p CK p CK p Dose Level: 0.15 Dosage Unit: mg/kg/day 0 4 21 12 00 03B3D 00 4D 0 0 0 0 1 2 1 1 1 0 0 4BlD 0 0 1 3 0 4D 0 0 0 0 2 0 2B2D 0 Bi p CK CK p BK CK p CK Dose Levelt 0.75 Dosage unit: mg/kg/day 1 1 1 2 0 4B2D 0 0 0 2 3 0 0 4D 0 3DlE 0 0 1 1 1 1 3 0 1B 0 0 1 1 1 3 0 2B3D 0 0 0 1 1 3 0 2B4D 0 CK BK p cx p BK Ai p CK p 660 Appendix 4 Individual Clinical Urinalysia Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS, T-6295) IN CYNOMOLGUS ANIMAL NUMBER ------ u VOL SP GR u PH ML -------- -------- -------- SULF-ONIC ACID MONKEYS Groupt 1 105508 105517 Io5sl9 105520 105526 105527 MEAN S.D. u Group: 2 105514 105515 105516 105521 a Dose Level: 0 46.0 40.0 60.0 43.0 52.0 44.0 1.023 1.026 1.017 1.023 1.026 1.031 47.5 7.31 6 1.024 .0046 6 Dose Level: 0.03 29.0 66.0 46.0 122.0 1.010 1.017 1.025 1.019 Dosage Unit; mg/kg/day 8.() 6.0 8.0 7.5 7.5 8.0 7.5 .77 6 Dosage Unit: mg/kg/day 8.0 8.0 7.5 7.5 MEAN S.D. N Group; 3 105505 105510 105518 105523 IOS524 105528 MEAN S.D. N 65.8 40.43 4 1.018 .0062 4 Dose Level; 0.15 241.0 48.0 106.0 72.0 42.0 98.0 1.005 1.010 1.017 1.010 1.021 1.018 101.2 73.16 6 1.014 .0061 6 7.8 .29 4 Dosage Unit: mg/kg/day 7.0 7.0 8.0 7.0 7.5 8.0 7.4 .49 6 a Sample collected on Day 92. 661 Appendix 4 individual Clinical Urinalygig Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFC)NIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNO14OLGUS MONKRYS ANIMAL NUMBER ------ U VOL ML -------- SP GR U PH ------- -------- Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Doge Level: 0.75 42.0 28.0 48.0 70.0 82.0 54.0 1.021 1.030 1.021 1.017 1.010 1.023 54.0 19.47 6 1.020 .0066 6 Dogage Unit: mg/kg/day 6.5 8.0 8.0 8.0 6.0 7.0 7.2 .88 6 662 Appendix 4 Individual Clinical Urinalysis Data Males Day 91 26-WEEK CAPSULE TOXICZTY STUDY WITU PLPRFLUOROOCTME SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ U PRO U GLU um U BILI U BLOOD UROBILI MG/DL -------- -------- -------- -------- -------- -------- Group: 1 Doze Level: 0 Dosage Unitz mg/kg/day 105508 10 - 105517 10 - 105519 10 - 105520 10 - 105526 10 - + :105527 10 - Grbupt 2 105514 105515 105516 105521 a Dose Levelz 0.03 0 10 10 0 Dosage Unit: mg/kg/day Group: 3 Dose Levelt 0.15 Dosage Unitt mg/kg/day 105505 0 - - - - - 105510 0 - - - - - 105518 0 - - - - - 105523 0 - - - - - 105524 10 - ++ - - 105528 0 - Group: 4 105506 105507 105509 105511 105512 105522 Dose Level: 0.75 10 10 0 0 0 10 Dosage Unit: mg/kg/day ++ a Sample collected on Day 92. 663 ANIMAL NUMBER ------ Group: 1 105508 105517 105519 105520 105526 105527 Group: 2 105514 105515 105516 105521 a Group: 3 105505 105510 105518 105523 105524 105528 Group. 4 IOSS06 Z05507 105509 105511 105512 105522 Appendix 4 Individual Clinical Urinalysis Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERPLUOROOCTARE SULPOWIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS URINE COMMENT PER HPF PER HPF PER HPF PER HPP PER LPF PER LPPI PER LPF2 Appi -------- ---------------- -------- -------- ---------------- -------- ------- Done Level: 0 Dosage Unitt mg/kg/day 0 0 0 3 0 3D2F 0 CK 0 0 2 3 0 4B 0 cx p 0 0 0 3 0 381D 1F BK - a 0 0 3 0 484D IE BK - 6 0 0 2 0 lB4D 0 cx - 0 0 0 2 0 4B4D 3E CL - Dose Level: 0.03 Dosage Unit: mg/kg/day 0 0 0 3 0 4B2E 0 0 0 0 3 0 4BID 0 0 0 1 3 0 1D 0 0 0 0 1 0 4B2E 0 Dose Level: 0.15 Dosage Unit: mg/kg/day OK BK CK CK Q 0 0 0 1 1 0 2 3 0 0 0 AJ PQ 0 0 0 3 0 0 3B 0 2BlE SK PO 0 1 0 3 0 0 BL 48 '0 AK PQ 0 0 1 2 0 0 0 CK p 0 0 0 2 0 3B2E ip BK Q Dose Level: 0.75 Dosage Unit: mg/kg/day 0 0 1 0 1 0 2 1 0 0 0 0 4B4D cx PO 0 0 0 3 0 ia CL 1B 0 BJ 0 0 0 2 0 3BIE 0 BL 0 0 1 2 0 0 0 Bi p 0 0 1 1 0 4D 0 Bi Q a Sample collected on Day 92. 664 Appendix 4 individual Clinical Urinalysin Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY W17H PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ u VOL SP GR u PH ML -------- -------- -------- Group: I 105529 105530 105531 105535 105544 105549 mm S.D. N Group: 2 105537 105541 105547 105550 ttm S.D. N Group: 3 105532 105536 105539 105545 105548 105552 MEAN S.D. N Dose Level, 0 45.0 67.0 62.0 229.0 65.0 92.0 1.016 1.020 1.019 1.006 1.018 1.012 93.3 69.15 6 1.015 .0053 6 Dose Level: 0.03 104.0 31.0 60.0 64.0 1.017 1.021 1.014 1.021 64.8 30.02 4 1.018 .0034 4 D086 Level: O.IS 102.0 74.0 56.0 48.0 61.0 38.0 1.011 1.012 1.026 1.014 1.020 1.028 63.2 22.56 6 1.018 .0073 6 Dosage Unit: mg/kg/day 8.0 8.0 slo 9.0 8.0 9.0 8.0 .00 6 Dosage Unit: mg/kg/day 7.0 7.5 7.0 8.0 7.4 .48 4 Dosage Unit: mg/kg/day 8.0 7.0 7.5 6.5 8.0 8.0 7.5 .63 6 665 Appendix 4 individual Clinical Urinalysis Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLE)OROOCTANE SULFONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NER4BER ------ U VOL SP GR U PH WL -------- -------- -------- ACID Group. 4 Dose Levelt 0.75 Dosage Unit: mg/kg/day 105533 105534 105536 105540 105542 105551 MEAN S.D. N 30.0 46.0 268.0 295.0 38.0 46.0 120.5 125.14 6 1.025 1.023 1.005 1.005 1.022 1.024 1.017 .0096 6 8.0 8.0 8.0 8.0 7.0 7.5 7.8 .42 6 666 Appendix 4 individual Clinical Urinalygig Data Females Day 91 26-WEEK ANIMAL NUMBER ------ CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANZ POTASSIUM SALT (PFOS; T-629S) IN CYNOMOLGUS SULFONIC MONKEYS ACID U PRO MG/DL -------- U GLU -------- U KET -------- U BILI -------- U BLOOD -------- UROBILI -------7 Group: 1 105529 IOS530 IOSS31 IOS535 105544L 105549 Dose Level: 0 10 - 10 - 10 - 10 - 10 - 0 Dosage Unit: mg/kg/day - Group: 2 Dose Level: 0.03 Dosage Unit: mg/kg/day 105537 0 - 105541 10 - + 105547 0 - 105550 30 - Group: 3 Dose Level: 0.15 Dosage unit: mg/kg/day 105532 10 - 105539 0 - + 105539 10 - 105545 0 - + 105548 10 - + 105552 10 - Group: 4 DOSS.Levelt 0.75 Dosage unit: mg/kg/day 105533 10 - + 105534 10 - 105536 0 - 105540 0 - 105542 10 - 105551 10 - 667 ,7' ANIMAL NUMBER ------ Group% 1 105529 105530 105531 105535 105544 105549 Group- 2 105537 105541 105547 105550 Group: 3 105532 105538 105539 105545 105548 105552 Group: 4 105533 105534 105536 105540 105542 105551 Appendix 4 Individual Clinical Urinalysis Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFORIC POTASSIUM SALT (PFOS; T-6295) IN CYNONOT-GUS MONKEYS ACID RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS URINE c PER HPF -------- PER HPF -------- PER HPF PER HPF -------- -------- PER LPF PER LPF1 -------- -------- PER LPF2 -------- APP1 -------- DoZe Level.- 0 Dosage Unit. mg/kg/day 0 0 0 3 0 3B4D 0 SK 4 0 0 3 0 3B4D 0 BL 0 0 0 3 0 4B2E 0 BL 0 0 1 3 0 2BlF 0 Bi 0 0 0 3 0 2B 0 BL 0 0 1 3 0 281D is BK Dose Level: 0.03 Dosage Unit: mg/kg/day 0 0 1 2 0 3BlD is BK 0 0 1 3 0 4B4D izip BL 0 0 0 3 0 3DID 0 BL p 4 0 1 3 0 3B 0 CL Dose Level: 0.15 Dosage Unit: mg/kg/day 0 1 4 3 0 lB4D 0 BK p 0 0 2 3 0 3D 0 BK 0 0 0 2 0 4B29 0 SL 0 0 1 1 0 0 0 BX 0 0 1 1 0 4B4D 0 DL 0 0 1 1 0 4BID in CL Dose Level: 0.75 Dosage Unit: mg/ko/day 0 3 1 3 0 4D 0 CR p 0 0 0 2 0 4B4D 0 BL 0 0 1 2 0 3D 0 Ai 0 0 2 3 0 0 0 AX 0 2 1 3 0 2B2D 0 BK p 0 0 1 3 0 381D 0 BL 668 Appendix 4 Individual Clinical Urinalysis Data males Day 153 26-WEEK CAPSULE POTASSIUM ANIMAL NUMBER ------ TOXICITY STUDY WITH PERFLUOROOCTANE SALT (PFOSI T-6295) IN CYNO14OLGUS U VOL SP GR u PH ML -------- -------- -------- SULFOUIC MONKEYS ACID Groul):.l 105508 105517 105519 105520 105526 105527 MEAN S.D. Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 105523 105524 105528 MEAN s.i). N Dose Level: 0 68.0 76.0 210.0 34.0 320.0 80.0 1.017 1.013 1.004 1.019 1.005 1.021 131.3 110.42 6 Dose Level: 1.013 .0072 6 0.03 56.0 46.0 34.0 84.0 1.017 1.020 1.028 1.017 55.0 21.32 4 1.020 OOS2 4 Dose Level% 0.15 360.0 92.0 66.0 140.0 44.0 125.0 1.004 1.009 1.014 1.008 1.022 1.011 137.8 114.54 6 1.011 .0062 6 Dosage Unit: mg/kg/day 7.5 7.0 7.5 6.5 6.5 7.5 7.1 .49 6 Dosage Uniti mg/ka/day 7.5 7.0 7.0 8.0 7.4 .48 4 Dosage Unit; mg/kg/day 7.5 7.0 7.0 7.0 7.0 7.0 7.1 .20 6 1%9 Appendix 4 individual Clinical Urinalysis Data males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ------ U VOL SP GR u PH ML -------- -------- -------- SULFONIC MONKEYS ACID Group: 4 105506 105507 105509 105511 105512 105522 MEAN S.D. N Dose Level: 0.75 80.0 200.0 32.0 390.0 280.0 98.0 1.012 1.008 1.026 1.003 1.005 1.013 190.0 136.48 6 1.011 .0082 6 Dosage Unit: mg/kgtday 7.0 7.5 6.0 7.0 7.5 7.5 7.1 .58 6 670 Appendix 4 individual Clinical Urinalysis Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME POTASSIUM SALT (PFOS. T-6295) IN cymoMotGUS SULFOMIC MONKEYS ACID ANIMAL NUMBER ------ U PRO MG/DL -------- U GLU -------- U KET -------- U BILI -------- U BLOOD -------- UROBILI -------- Group: 1 105508 105517 105519 105520 105526 105527 Group: 2 105514 105515 105516 105521 Group: 3 105505 105510 105518 105523 105524 105528 Group: 4 105506 105507 105509 iossii 105512 105522 Dose Level: 0 0 - 0 - 0 - 0 - 0 - 0 - Dose Level; 0.03 0 - 0 - 0 - 0 - Dooe Level; 0.15 0 - 0 - 0 - 0 - 0 - 0 - Dose Level: 0.75 0 - 0 - 10 - 0 - 0 - 0 - Dosage unit: mg/kg/day ++ + Dosage unit: mg/kg/day ++ + ++ Dosage Units mg/kg/day + ++ Dosage unit: mg/kg/day ++ 671 ANIMAL NUMBER Group: 1 105508 105517 105519 105520 105526 105527 Group: 2 105514 105515 105516 105521 Group: 3 105505 105510 105518 105523 105524 105528 Group: 4 105506 105507 105509 105511 105512 105522 Appendix 4 individual Clinical Urinalysis Data males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS MOMMYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS URINE C PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 APP1 -------- -------- -------- -------- -------- -------- -------- -------- Dose Level: 0 Dosage Unit: mg/kg/day 0 0 1 3 0 4B 0 BK 0 0 1 2 0 0 0 BK p 0 0 0 2 0 0 0 AJ 0 0 1 3 0 0 a BK 0 0 1 3 0 0 0 AK 0 0 0 3 0 4B4D 0 BL Dose Level: 0.03 Dosage Unit- mg/kg/day 0 0 0 3 0 3BlD. 1B BK PO 0 0 1 3 0 lBlD 1E BK PO 0 0 1 3 0 dBlD 0 BK PQ 0 0 1 3 0 4B4D 0 BL Dose Level: 0.15 Dosage unit: mg/kg/day 0 0 1 3 0 0 0 AK 0 0 1 3 0 0 0 BK 0 0 0 3 0 4B 0 BK 0 1 1 3 0 0 0 BK 0 0 0 1 2 0 0 0 BK - 0 1 1 3 0 0 0 BK Q Dose Level: 0.75 Dosage Unit: mg/kg/day 0 0 1 3 0 2B 0 0 0 0 2 0 0 0 0 1 1 3 0 0 0 0 0 0 2 0 0 0 0 0 1 2 0 0 0 0 0 1 3 0 0 0 BK AK BK p AX AK BK 672 Appendix 4 individual Clinical Urinalysis Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID ANIMAL NUMBER ------ U VOL SP GR U PH ML -------- -------- -------- Group: 1 105529 105530 105531 105535 105544 105549 Dose Level: 0 44.0 36.0 36.0 145.0 100.0 150.0 1.022 1.024 1.023 1.006 1.011 1.007 Dosage Unit: mg/kg/day 7.5 8.0 7.5 7.0 7.5 7.5 MEAN S.D. N 85.2 53.91 6 1.016 .0084 6 7.5 .32 6 Group: 2 Dose Level: 0.03 Dosage unit: mg/kg/day 105537 105541 105547 105550 110.0 1.013 7.0 40.0 1.020 7.0 26.0 1.017 6.5 66.0 1.016 7.5 MEAN S.D. x 60.5 36.93 4 1.016 .0029 4 7.0 .41 4 Gioup: 3 Dose Level: 0.15 Dosage unit: mg/kg/day 105532 105538 105539 105545 105548 105552 MEAN S.D. N 44.0 46.0 54.0 46.0 28.0 26.0 40.7 11.15 6 1.023 1.027 1.018 1.018 1.022 1.027 1.022 .0040 6 7.0 7.0 7.0 7.0 7.5 7.0 7.1 .20 6 673 Appendix 4 individual Clinical Urinalysis Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ U VOL SP GR u PH ML -------- -------- -------- Group: 4 Dose Level: 0.75 Dosage Units mg/kg/day 105533 105534 105536 105540 105542 105551 30.0 1.025 7.0 52.0 1.011 8.0 110.0 1.012 7.5 270.0 1.005 6.0 36.0 1.021 7.0 36.0 1.026 7.0 MEAN S.D. N 89.0 93.46 6 1.017 .0085 6 7.1 .66 6 674 Appendix Individual Clinical Urinalysia Data Females Day 153 26-WEEK ANIMAL NUMBER ------ CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS U PRO MG/DL -------- U GLU -------- U KET -------- U DILI -------- U BLOOD -------- UROBILI -------- Group: 1 105529 105530 105531 105535 105544 105549 Group: 2 105537 105541 105547 105550 Group- 3 105532 105538 105539 105545 105548 105552 Group: 4 105533 105534 105536 105540 105542 105551 Dose Level: 0 10 - 10 - 0 - 0 - 0 - 0 - Dose Level: 0.03 0 - 30 - 10 - 0 - Dose Level: 0.15 0 - 0 - 0 - 0 - 10 - 0 - Dose Level: 0.75 0 - 0 - 0 - 0 - 0 - 0 - Dosage Unit: mg/kg/day + + + Dosage Unit: mg/kg/day + ++ + Dosage unit.- mg/kg/day + + ++ Dosage Unitt mg/kg/day +++ + ++ ++ 675 ANIMAL NUMBER ------ Group: 1 105529 105530 105531 105535 105544 105549 Group: 2 105537 105541 105547 105550. Group: 3 105532 105538 105539 105545 105548 105552 Group: 4 105533 105534 105536 105540 105542 105551 Appendix 4 individual Clinical Urinalysis Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID RBC PER HPF -------- WBC P-E-R--H-PF- - EPITH BACT CASTS CRYSTALS CRYSTALS URINE c PER HPF PER HPF PER LPF PER LPF1 PER LPF2 APP1 -------- -------- -------- --- ---- -------- -------- -- Dose Level: 0 Dosage Unit: mg/kg/day 2 1 0 3 0 381D 0 BL BL 0 1 0 3 2 0 0 4B4D 0 4B4D 2E4F BL p 0 0 0 0 0 1 2 0 0 0 BK 00 00 12 33 00 40B 0 BBLK Dose Level: 0.03 Dosage unit- mg/kg/day 0 0 1 3 3 0 0 284D 0 0 0 4 0 1 1 1 1 3 0 3B2E 0 0 0 2 3 0 0 0 EK CK p BL p BK Dose Level: 0.15 Dosage Unit: mg/kg/daY 0 & 2 2 0 0 0 0 0 1 1 00 I1DD 00 00 10 32 33 0 4D 0 0 1 1 3 0 484D 0 0 0 1 3 0 4D 0 BK p CK BK p BK p BL ex p Dose Level: 0.75 Dosage unit: mg/kg/day 0 1 1 3 0 2B2D 0 BK 0 0 1 3 0 0 2B4D 0 BK 4B3D IE BL 0 1 1 2 1 0 0 0 AK 0 0 1 2 2 1 3 0 2B4D 0 BK 0 1 1 3 0 3B4D 0 CK 676 Appendix 4 individual Clinical Urinalysis Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOST T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID ANIMAL NUMBER ------ U VOL ML -------- SP GR -------- U PH -------- Group: 1 105508 105517 105519 105520 105526 105527 MEAN S.D. N Group.- 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 105505 105510 105518 ioSS23 105524 105528 MEAN S.D. N Dose Level: 0 184.0 49.0 62.0 102.0 242.0 58.0 1.006 1.021 1.012 1.013 1.006 1.023 116.2 79.33 6 1.014 .0072 6 Dose Level: 0.03 94.0 52.0 54.0 102.0 1.014 1.019 1.018 1.016 75.5 26.20 4 1.017 .0022 4 Dose Levelt 0.15 368.0 122.0 78.0 21.0 49.0 96.0 1.003 1.012 1.016 1.017 1.015 .1.016 122.3 125.43 6 1.013 .0053 6 Dosage unitt mg/kg/day 8.0 7.5 8.0 8.0 8.0 8.0 7.9 .20 6 Dosage Unit: mg/kg/daY 8 .0 7'.5 8.0 8.0 7.9 .25 4 Dosage Unit: mg/kg/daY 8.0 8.0 8.5 6.0 6.5 8.0 7.5 1.00 6 677 Appendix 4 individual Clinical Urinalysis Data males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ U VOL SP GR U PH ML -------- -------- -------- Group: 4 105507 105511 105512 105522 MEAN S.D. N Dose Levelt 0.75 280.0 96.0 36.0 72.0 1.005 1.017 1.018 1.012 121.0 108.83 4 1.013 .0059 4 Dosage Unitt mg/kg/day 7.5 8.0 6.5 7.0 7.2 .65 a 678 Appendix 4 individual Clinical Urinalysig Data males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ U PRO U GLU U KET U BILI U BLOOD MG/DL -------- -------- -------- -------- UROBILI Group: 1 Dose Level: 0 Dosage unit: mg/kg/day 105500 10 -- - - 7 110055551179 1100 - - - 105520 10 - - - 105526 10 - - - 105527 10 - + - Group- 2 105514 105515 105516 105521 Dose Level: 0.03 10 - 10 - 10 - 10 - Dosage unit.- mg/kg/day - - - - - - - - - - - - Group; 3 105505 105510 105518 105523 105S24 105528 Dose Level: 0.15 10 - 10 - 10 - 10 - 10 - 10 - Dosage unit: mg/kg/day - - - - - - ++ - Group: 4 105507 1055ll iO55l2 105522 Dose Level: 0.75 10 - 10 - 10 - 10 - Dosage unit: mg/kg/day - - - - - - - - 679 ANIMAL NUMBER ------ Group: 1 105508 105517 105519 105520 IOS526 105527 Group: 2 105514 105515 105516 105521 Group: 3 105505 105510 105518 105523 105524 105528 Group: 4 105507 105511 105512 105522 Appendix A individual Clinical Urinalysis Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID RBC WBC PER HPF PER HPF -------- -------- EPITH BACT PER HPF PER HPF -------- -------- CASTS CRYSTALS PER LPF PER LPFI -------- --- ---- CRYSTALS PER LPF2 ------- URINE C Appi -------- --- Dose Level: 0 Dosage unit: mg/kg/daY 0 0 0 3 0 2BlZ 0 BK 0 0 0 2 0 3B3D 0 4B 0 DL BK 0 0 0 0 3 3 0 0 3BID 0 BL 0 0 0 1 0 3 0 2B 0 AK 0 0 0 3 0 4B4D 0 BL Dose Level: 0.03 Dosage Unit: mg/kg/day 0 0 0 2 0 2B2E 0 4BlE 0 BK BK 0 0 0 0 0 1 3 3 0 0 2B 0 BK 0 0 0 3 0 4B 0 BL Dose Level: 0.15 Dosage unit: mg/kg/day 0 0 0 3 0 2B 0 0 0 1 3 0 2BIE 0 0 0 0 3 0 4B4D 0 0 0 0 1 0 1B 0 0 0 0 3 0 0 0 0 0, 0 1 0 4BlE 0 AX SK BK Bi p BK BL Dose Level: 0.75 Dosage Unit: mg/kg/day .0 0 0 1 0 0 0 0 0 1 22 00 40B 00 0 0 0 0 0 1 2 0 2D 0 AJ Q BK Q Bi p ax K 680 Appendix 4 Individual Clinical urinalysia Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ U VOL SP GR u PH ML -------- -------- -------- Group: I 105529 105530 105531 105535 105544 105549 S.D. N Group: 2 105537 105541 105547 105550 mm S.D. N Group: 3 105532 105538 105539 105545 105548 105552 "M S.D. Dose Levels 50.0 62.0 57.0 159.0 86.0 100.0 0 1.020 1.015 1.023 1.009 1.017 1.013 85.7 40.59 6 1.016 .0050 6 Dose Level: 0.03 100.0 38.0 95.0 64.0 1.013 1.020 1.009 1.020 76.2 31.48 4 1.016 .0054 4 Dose Level: 0.15 118.0 61.0 70.0 66.0 82.0 43.0 1.010 1.021 1.022 1.013 1.014 1.023 73.3 25.33 6 1.017 .0055 6 Dosage 8.0 8.0 8.5 8.0 8.0 8.0 Unit: mg/kg/day 8.1 .20 6 Dosage Unit: mg/kg/day 7.0 7.5 8.0 8.0 7.6 .48 4 Dosage Unit: mg/kg/day 8.0 8.0 8.0 7.5 8.0 B.o 7.9 .20 6 681 Appendix 4 individual Clinical Urinalysis Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ACID ANIMAL NUMBER ------ U VOL ML -------- SP GR -------- U PH -------- Group: 4 105533 105534 105536 105540 105542 105551 MEAN S.D. N Dose Level: 0.75 47.0 92.0 72.0 450.0 84.0 56.0 1.016 1.015 1.017 1.003 1.018 1.018 131.8 156.54 6 1.014 .0058 6 Dosage unit: mg/kg/daY 7.5 8.0 8.0 7.5 8.0 8.0 7.8 .26 6 682 Appendix 4 individual Clinical Urinalysis Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ANIMAL NUMBER ------ U PRO MG/DL -------- U GLU -------- U KET ------- U BILI -------- U BLOOD UROBILI ------- -------- Group: 1 105529 105530 105531 105535 105544 105549 Group: 2 Dose Level: 0 10 - 10 - 10 - 10 - 10 - 10 Dose Level: 0.03 Dosage unit: mg/kg/day - - - - - - - - - - - - - - - Dosage Unit: mg/kg/day 105537 10 ++ 105541 10 ++ 105547 10 105550 10 Group: 3 Dose Level: 0.15 Dosage unitt mg/kg/day 105532 10 - 105538 10 - 105539 10 - 105545 10 - 105548 10 - 105552 10 - Group: 4 Dose Level: 0.75 Dosage units mg/kg/day 105533 3100 -- + 110055553346 10 - 105540 10 - 105542 10 - 105551 10 683 Appendix 4 Individual Clinical Urinalysis Data AN114AL NUMBER Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH pERpLUOROOCTAKE POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID RSC WBC EPITH BACT CASTS CRYSTALS CPREYRSTALLPSF2 UARPIPNIE C PER HPF PER HPF PER HPF PER HPF -------- -------- ------- PER LPF PER LPF1 -------- -------- ------ - ------ -------- Group: I Dose Level: 0 Dosage Unit- mg/kg/day 105529 0 0 1 3 0 4BlD 0 4B2D 0 DL DL 105530 0 0 0 1 3 3 0 ia 4BIE 0 BK 105531 0 0 0 1 3 0 4D 0 BK BL 110055553454 00 0 1 3 0 42BBID 00 BK 105549 0 1 1 3 0 Group: 2 Dose Level: 0.03 Dosage unit: mg/kg/day 105537 0 1 1 3 0 0 3B28 0 3BIR 0 105541 0 1 1 1 3 3 0 4B 0 105547 0 105550 0 0 0 1 3 0 4BlE 0 SK BL BK p BL Group- 3 Dose Level: 0.15 Dosage unit- mg/kg/day 105532 0 3 0 3 0 2B29 0 BK AB2B IF BL 105538 0 0 1 2 1 0 0 3BlE 0 BL 110055553495 00 00 011 23 00 23B82D 00 BBKK BL 105548 0 105552 0 0 1 1 3 0 3B3D 0 Group: 4 Dose Levelt 0.75 Dosage unit: mg/kg/day 105533 2 0 1 3 0 0 0 0 BK BL 105534 0 1 1 2 3 2 0 0 3B 4B3D 0 BL 110055553460 00 00 10 23 00 14BB 00 ABKX 3B3D 0 BL 105542 0 0 105551 0 1 1 3 0 684 APPENDIX 4 Individual clinical Urinalysis Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WM PERFLUOROOCTANE SULPoNrc POTASSIUM SALT (PPOS, T-629S) IN CYNOMOLGUS ANIMAL NUMBER ------ U VOL ML -------- SP CR -------- U PH -------- AcrD Group: I 105520 105526 MEAN S.D. N Group: 3 IOS505 IOSS23 MEAN S.D. N Group: 4 105511 ZOSS22 MEAN S.D. N Dose Level: 0 162.0 197.0 1.010 1.010 179.5 24.7S 2 1.010 .0000 2 Dose Level: 0.15 296.0 183.0 i.oos 1.009 239.5 79.90 .2 1.007 .0028 2 Does Level: 0.7S 62.0 113.0 1.011 1.015 87.S 36.06 2 1.013 .0028 2 Dosage Unit: mg/kg/day 7.5 7.0 7.2 .3S 2 Dosage Unit: mg/kg/day ?.S 7.5 7.5 .00 2 Dosage Unit: mg/kg/day 6.5 7.5 7.o .71 2 26-WEEK ANIMAL NUMBER ------ APPENDIX 4 individual clinical Urinalysis Data males Day 217 CAPSULE TOXICITY STUDY WITH PEPYLUOROOCTANE SULPONIC ACID POTASSIUM SALT IPFOS; T-6295) IN CYNOMOLGUS U PRO MG/DL -------- U GLU -------- U F.ET -------- U BILI -------- U BLOOD -------- UliOBILI -------- Group: I 105520 105526 Group: 3 105505 iOSS23 Group-. 4 iossii iOS522 Dose Level: 0 0 0 Doze Level; 0.15 0 0 Dose Level: 0.7S 0 0 Dosage Unit: mg/kg/day Dosage Unit: mg/kg/d@Ly bosace Unit: molka/day + ANIKAL NUMBER ------ Group: I 105520 105S26 Group: 3 105SOS 105523 Group: 4 105511 IOSS22 APPENDIX 4 Individual clinical Urinalysis Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTARE SULFONIC ACID POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS RBC PER HPF -------- WBC PER HPF -------- EPITH PER HPF -------- BACT PER HPF -------- CASTS CRYSTALS PER LPF PER LPF1 -------- -------- UR1142 Appi -------- COM14ENTS -------- Dose Level: 0 Dosage Unit: mg/kg/day 0 1 0 1 0 4B BK 0 0 1 2 0 4B Bi Q Dose Level: 0.15 Dosage Unit: mg/kg/day 0 0 0 2 0 2B AJ (1 0 0 2 0 2B AK Q Dose Level: 0.75 Dosage Unit; mg/kg/day 0 0 1 3 0 35 DK 0 0 0 3 0 3B BK APPENDIX 4 Individual Clinical Urinalysis Data Famalos Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ------ U VOL SP GR u PH fiL ------- -------- -------- Group: 1 lo5s29 TOSS49 MP-MI S.D. Group: 3 105539 105552 MEAN S.D. N Group: 4 IDS533 IOS542 MEAN S.D. Dose Level: 0 88.0 198.0 1.020 1.009 143.0 77.78 2 1.014 .0078 2 Dose Level: 0.15 178.0 64.0 1.015 i.ois 121.0 90.61 2 1.015 .0000 2 Dos* Level: 0.75 63.0 115.0 1.015 1.015 89.0 36.77 2 1.015 .0000 2 Dosage Unit: mg/kgiday 8.0 7.5 7.8 .35 2 Dosage Unit: mg/kg/day .7.5 7.0 7.2 .35 2 Dosage Unit: mg/ka/day 7.o 8.0 7.S .71 2 26-WEEK ANIMAL NUMBER ------ Group: I IOSS29 iOSS49 Group; 3 JOSS39 JOSSS2 Group: 4 IOSS33 105542 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 217 CAPSULE TOXICITY STUDY WITM PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ACID u PRO MCIDL -------- U GLU -------- U KET -------- U BILI -------- U BLOOD UROBILI ------- -------- Dose Level: 0 Dosage Unit: mgikg/day 0 0 Dose Level: 0.15 + Dosage Unit: mg/ka/day 10 10 + Dose Level: 0.75 Dosage unit: mg/ko/daY 0 + 0 AN114AL NUMBER ------ Group: I IOSS29 IOSS49 Group: 3 105539 105552 Group: 4 IOSS33 105S42 APPENDIX 4 Individual Clinical Urinalysig Data Females Day 217 26-WEEK P-BC PER HPF -------- CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS WBC PER HPF -------- EPITH PER HPF ------ - BACT PER HPF -------- CASTS CRYSTALS PER LPF PER LPFI -------- ------- URINE Appi -------- COMMENTS -------- Doze Level: 0 Dosage Unit: mg/kg/day 0 0 1 3 0 4B CK 3B AK 0 0 0 3 0 Done Level- O.lS Dosage unit: ma/kg/day 4 u 1 3 0 4B3E BK 4B BK 0 0 1 3 0 Dose Level: (I.7S Dosage Unit: mg/kg/day 0 0 1 3 0 4B BK p BK 0 0 0 3 0 3B APPENDIX 4 Individual Clinical Urinalysis Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS; T-62951 IN CYNOMOLCUS ANIMAL NUMBER ------ U VOL SP GR U PH ML -------- -------- -------- ATID Group: I IOSS20 105526 MEAN S.D. N Group: 3 105sos 105523 MEAN S.D. N Group: 4 iossli IOSS22 MEAN S.D. N Dose Level: 0 202.0 189.0 1.008 1.010 195.5 9.19 2 1.009 .0014 2 Dose Level: 0.15 290.0 -102.0 1.005 1.014 196.0 132.94 2 1.010 .0064 2 Dose Level: 0.75 62.0 104.0 1.014 1.020 83.0 29.70 2 1.017 .0042 2 Dosage Unit: mg/kv/day 7.S 8.0 7.8 .35 2 Dosage Unit: mg/kg/day 7.5 7.S 7.5 .00 2 Dosage Unit: mg/kg/day 7.5 8.0 7.8 .35 2 26-WEEK ANIMAL NUMBER ------ Group-. 1 IOSS20 105526 Group: 3 105505 ZOSS23 Group: 4 iossii IOSS22 APPENDIX 4 individual clinical Urinalysis Data Males Day 245 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS u PRO MA.,DL -------- U GLU -------- U KET -------- U BILI -------- U BLOOOD UROBILI -------- -------- Dose Level: 0 (i 0 Dosage Unit: mg/kg/day Dor-e Level: 0.15 0 0 Dosage Unit: mg,-'kgl;dal, Doce Level: 0.7S 0 10 Dosage Unit: mg/kc/day AN114AL NMBER ------ Group: I IOSS20 IOSS26 Group: 3 105505 105S23 Group: 4 105511 105522 APPENDIX 4 Individual Clinical Urinalysis Data males Day 24S 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTPJ;E SULFONIC POTASSIUM SALT IPFOS; T-6295) IN CYNOMOLGUS ACID PJBC WBC PER HPF PER HPP -------- ------- EPITH PER HPF -------- BACT PER HPF -------- CASTS CRYSTALS PER LPF PER LPF1 ------- -------- CRYSTALS PER LPF2 -------- URINE APP1 -------- COMi4 ---- Dose Level: 0 Dosage unit: mg/kg/day 0 0 1 3 0 0 0 ID (1 0 o@ 3 0 Dose Level: 0.15 Dosage Unit: mgikg!day 0 0 0 3 0 0 0 2B2F 0 0 1 1 2 IH Dose Level: 0.75 Dosage unit: mg/kg!day 0 0 1 2 0 3D 0 4B 0 0 0 0 3 0 AJ AJ AJ PQ BJ BL APPENDIX 4 Individual clinical Urinalysis Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PMTPLUOROOCTANE SULPOIIIC ACID POTASSIUM SALT (PFOS, T-6295) III CYNOMOLGUS ANIMAL NUMBER ------ U VOL SP GR U PH UL -------- -------- -------- Group: I 105529 105549 MEAN S.D. Croup: 3 rOSS39 IOSS52 NPJW S.D. N Group: 4 105533 105542 MEAN S.D. N Dose Level: 0 46.(1 las.0 1.026 1.010 117.0 11)0.41 1.018 .0113 2 DOSO Level: O.IS 176.0 87.0 1.015 i.oia 131.5 62.93 2 1.016 .0021 2 Dose Level: 0.75 57.0 126.0 1.014 1.019 91.5 48.79 2 1.016 .0035 2 Dosage Unit: mg!kg!day 8.0 8.0 8.0 .00 2 Dosage Unit: ing/kg/day 7.o 7.5 7.2 .35 2 Dosage Unit: mfjlkglday 7.S 8.0 7.8 .35 2 APPENDIX 4 26-WEEK ANIMAL NUMBER ------ Group: I 105529 105549 Group: 3 IOSS39 105552 Group: 4 105533 105542 Individual clinical Urinalysis Data Females Day 245 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS: T-6295) IN CyNoMOLGUs u PRO MC/DL -------- U CLU -------- U KET -------- U HILI -------- U BLOOD -------- UROBILI -------- Dose Level: 0 Dosage Unit: mg.,'kg.;day 10 0 Do-.,:L&zvol: 0.15 Dosage Unit: Fng.'kaiday 0 0 Dose Level: 0.75 10 0 Dosage Unit: mg.;kg/day + AtilMAL TIUMBER Group: 1 IOSS29 IOSS49 Group- 3 105539 iOSS52 Group: 4 105533 I05S42 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 24S 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTA14B SULFONIC ACID POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLCUS RBC PER MPF ---- --- WBC PER HPF ------- EPITH PER HPP -------- BACT PER HPF -------- CASTS PER LPF ---- --- CRYSTALS CRYSTALS URINE CO@IN PER LPFI PER LPF2 APP1 -------- -------- -------- ---- Dose Level: 0 Dosage Unit: mg/kg!day 0 3 0 3BlD IE BK - - 0 0 0 0 1 3 0 2B 0 Bi Dose Level: O.lS Dosage Unit: mglkg!day 0 0 1 3 0 0 IB 0 4BlZ 0 0 0 1 1 BJ - BL - Dose level: 0.75 Dosage unit: mg/kg!day - 00 10 11 32 00 23BB2IED 02P BBKL - APPENDIX 4 Individual Clinical Urinalysis Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PPOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL SP GR u PH ---M-L-- - -------- -------- ACID Group: I 105520 105526 MEAN S.D. N Group- 3 iossos ZOSS23 MEAN S.D. N Group: 4 105511 105522 MEAN S.D. N Dose Level: 0 248.0 320.0 1.004 1.003 284.0 SO.91 2 1.004 .0007 2 Dose Lovelt O.lS 354.0 114.0 1.004 1.010 234.0 169.71 2 1.007 .0042 2 Dose Level: 0.75 32.0 103.0 1.026 1.011 67.5 so.20 2 1.018 .0106 2 Dosage Unit: mg/kg/day 6.5 7.0 6.8 .3S 2 Dosage unit: mo/ku/day 7.5 7.0 7.2 .35 2 Dosage Unit: mo/kg/day 6.5 7.5 I.o .71 2 26-WEEK ANIMAL NUMBER ------ Group: I 105520 105526 Group: 3 rossos iOSS23 Group: 4 iossii IOSS22 APPENDIX 4 individual clinical Urinalysis Data males Day 274 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPOZIZC ACID POTASSIUM SALT (PPOS; T-6295) IN Cl't4Ot4OL(;US U PRO MG/DL -------- U GLU -------- U KET -------- U BILI -------- U BLOOD -------- UROBILI -------- Dose Level: 0 0 0 Dose Level: 0.15 0 10 Dose Level: 0.7S DoeaCra Unit: mg.lkg/day Dosage Unit: mg.,'kg/day +++ Dosage Unit: mg!kg-day 10 + 0 ANIMAL NUMBER ------ Group: 1 105520 105@26 Group: 3 10550S 105523 Group: 4 IOS511 105S22 APPENDIX 4 Individual Clinical urinalysis Data Males Day 214 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CY140HOLGUS RBC WBC EPITH BACT CASTS CRYSTALS URINE APPI PER HPF PER HPF PER HPF PER HPF -------- PER LPF -------- PER LPF1 -------- ------- -------- -------- -------- C014MEHTS -------- Dose Level: (i Dosage Unit: mg/kg/daY 00 00 01 32 00 00 AAJJ Dose Level: 0.15 0 0 0 0 Dosage Unit: mvikcf/day 0 3 0 0 0 3 0 0 AJ Bi PQ Dose Level: 0.7S Dosage Unit: mglkg/day 00 00 00 23 00 l1BB4E BBii APPENDIX 4 individual Clinical Urinalysis Data Females Day 274 26-WEEK CAPSULE ToxicrTY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT (PPOS; T-629S) IN CYZIOMOLGUS ANIMAL IIUMBER ------ U VOL ML -------- SP GR -------- u PH -------- ACID Group: I IOSS29 106549 MEAN S.D. Group: 3 IOSS39 I055S2 MEAN S.D. Group: 4 105533 105S42 MEAN S.D. N Dose Level: 0 118.0 16S.0 1.007 1.005 141.5 33.23 2 1.006 .0014 2 Dose Level: 0.15 90.0 37.0 1.016 1.023 63.5 37.48 2 1.020 .0050 2 Dose Level: 0.7S 23.0 106.0 1.011 1.010 64.5 58.69 2 1.010 .0007 2 Dosage Unit: mg/kg/day 7.S 8.0 7.8 .3S 2 Dosage Unit: mg/kg/day 7.5 7.5 7.5 .00 2 Dosage Unit: mgiko/day 8.0 6.5 7.2 1.06 2 26-WEEK ANIMAL NUMBER ------ Group: I iOSS29 105549 Group: 3 iOSS39 iOSS52 Group: 4 105533 JOSS42 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 274 CAPSULE TOXICITY STUDY WITH PEP.FLUOROOCTAIIE SULFONIC ACID POTASSIUM SALT (PFOS; T-629S) IN CYI]OI40t.GUS U PRO MG/DL -------- U GLU ------ - U KET U BILI -------- -------- U BLOOD UROBILI ------- -------- Dose Level: 0 Dosage unit: mg/kg!day 0 0 Dose Level: 0.15 Dosage Unit: mg.!kg.'day LO 10 Dose Level: 0.7S ++ Dosage unit: mg,'kg!-'clay 10 0 ++ ANIMAL NUMBER ------ Group: 1 105529 105549 Group: 3 105539 105552 Group: 4 105533 105542 APPENDIX 4 individual clinical Urinalysis Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PE"LUOROOCTANE SULFONIC ACID POTASSIUW SALT (PFOS; T-629S) Ili CYNOMOLGUS RBC PER HPF -------- WBC PER HPF -------- EPITN ' BHCT PER HPF PER HPF -------- -------- CASTS PER LPF -------- CRYSTALS PER LPFI -------- URINE "Pi -------- COMMENTS -------- Dose Level: 0 Dosage Unit: mg/kg.;day 0 0 1 3 0 0 AJ p 0 0 1 3 0 it) Ai Dose Level: 0.15 Dosage Unit: ma.;kgt'day 0 1 1 3 0 lB2E BJ 0 0 1 3 0 4B BL Dose Level: 0.75 Dosage Unit: mg/kg!day 0 0 0 3 0 4B BL 0 0 1 3 0 1B Bi p APPENDIX 4 Individual clinical Urinalysin Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NU14BER ------ U VOL ML -------- SP GR -------- U PH -------- Group- I Dose Level: 0 Dosage Unit; mgikg/day 105520 IOSS26 MEAN S.D. N Group: 3 105505 105523 116.0 476.0 1.015 1.002 296.0 254.56 2 1.008 .0092 2 Dose Levelt 0.15 166.0 33.0 1.009 1.023 6.5 7.0 6.8 .35 2 Dosage Unit% mg/kg/day 7.0 6.0 MEAN S.D. N Group: 4 iossii ro5522 99.5 94.05 2 1.016 .0099 2 Dose Level: 0.75 51.0 44.0 1.013 1.026 6.s .71 2 Dosage Unit: mg/kg/day 6.0 6.0 MEAN S.D. N 47..5 4 95 2 1.020 .0092 2 4.o .00 2 APPENDIX 4 individual Clinical Urinalysis Data Males Day 322 26-WEEK ANIMAL NUMBER ------ CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS: T-6295) IN CYNONOLGUS U PRO U GLU U KET U BILI U BLOOD UROBILI MGIDL -------- -------- -------- -------- -------- -------- Group: I 105520 iOSS26 Group: 3 Dose Level: 0 0 0 Dose Level: 0.15 Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day 105505 105523 Group: 4 0 0 Dose Level: 0.75 Dosage Unit: mg/kg/day 105511 0 105S22 0 ANIMAL NUMBER ------ Group: 1 iOSS20 105526 Group.- 3 105505 105523 Group: 4 lossil ZOSS22 APPMMIX 4 Individual Clinical Urinalysis Data Males Day 322 26-WEEK RSC PER HPF -------- CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC POTASSIUM SALT IPPOS; T-6295) IN CYNOMOLCUS ACID WBC PER HPF -------- EPITH PER HPF -------- BACT PER HPF -------- CASTS PER LPF -------- CRYSTALS PER LPF1 -------- URINE APPI ---- --- CONHENTS -------- DOSO Level: 0 Dosage Unit: mg/kg/day 0 0 1 1 0 1B 0 (1 1 1 0 0 Dose Level: (1-15 Dosage Unit: mg.;kg/day 0 3 0 3B 0 3 0 2B Dose Level; 0.7S Dosage Unit: mg/kg/day 0 1 1 2 0 2B 0 0 0 2 0 0 AJ Q Bi si Q BJ Q APPENDIX 4 Individual Clinical Urinalysis Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PEIZFLUOIZOOC7ANE SULFONIC POTASSIUM SALT (PPOS; T-629S) iii cyNomoLGus ACID ANIMAL WA49ER ------ U VOL ML -------- SP GR -------- U PH -------- Group: I 105529 105549 Dose Level: 0 87.0 354.0 1.010 1.003 Dosage Unit: mg/kg/day 8.0 8.0 14mi 220.5 188.80 2 1.006 .0050 2 8.0 .00 2 Group: 3 Dose Level: 0.15 Dosage Unit: mg!kgiday 105539 105552 MEAN S.D. N Group: 4 105533 105542 MEAN S.D. N 76.0 42.0 1.015 1.021 59.0 24.04 2 1.018 .0042 2 Dose Level: 0.75 71.0 113.0 1.017 1.012 92.0 29.70 2 1.014 .0035 2 7.0 6.0 6.5 .71 2 Dosage Unit: mg/kg/day 6.5 7.0 6.8 .35 2 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 322 26-WEEK ANIMAL IIUMBER ------ CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPOVIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS U PRO* U GLU MG/t)L --------- -------- u FM -------- U BILI -------- U BLOOD -------- UROBILI -------- Group: I 105529 IOSS49 Group: 3 105539 IOSS52 Dose Level: 0 0 10 Dose Level: 0.15 0 0 Dosage Unit: mg/kg.,'day ++ Dosage Unit: mo/kgiday Group: 4 105533 rOSS42 Doe* Lev*l: 0.75 10 0 Dosage Unit.- mg/kg/day ++ JU41MAL NUMBER ------ Group- I IOSS29 IOSS49 Group: 3 105539 105552 Group: 4 105S33 IOSS42 APPENDIX 4 individual Clinical Urinalysis Data Females Day 322 26-WEEK C"SULE TOXICITY STUDY WITH PE"LUOP.OOCTJUIE SULFONIC ACID POTASSIUM SALT (PPOS; T-629S) IN CYNOMOLGUS RSC PER HPF -------- vh3c PER HPF -------- EPITH PER HPP -------- BACT PER MPF -------- CASTS PER LPF -------- CRYSTALS PER LPF1 -------- URI14E COMI.IENTS APP1 -------- -------- Dose Level: 0 Dosage Unit: mg/kg/day 0 1 1 2 0 2B Bi 0 0 1 3 0 0 AJ Dose Level- (I.lS Dosage Unit: mglkg.lday 0 1 1 3 0 1D BK 0 0 1 3 0 IB ci Dose Level: fi.75 Dosage Unit: mg/kg/day 0 1 1 2 0 0 0 1 1 1 0 0 APPENDIX 4 Individual Cl:inicalUrinalysis vat& Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PE"LUoRoocTmE OuLpoNic ACID POTASSIUM SALT (PFOS, T-6295) IN CYNO14oLGUS ANIMAL NUMBER ------ U VOL ML -------- SP GR -------- U PH -------- Group: 1 105520 rOSS26 14PAN S.D. Group: 3 I05sos IOS523 MEAN S.D. N Group: 4 105511 105522 MEAN S.D. Dose Level: 0 149.0 264.0 1.019 1.015 206.5 $1.32 2 1.017 .0028 2 Dose Level: 0.15 82.0 67.0 1.018 1.018 74.5 10.61 2 1.018 .0000 2 Dome Level: 0.7S 100.0 80.0 1.015 1.022 90.0 14.14 2 1.018 .0050 2 Dosage Unit.- mg/kg/day 8.0 7.S 7.9 .35 2 Dosage Unit: mg/kgr/day 8.0 7.0 7.5 .71 2 . D Osage unit.- mo/ka/day 7.5 6.0 6.8 1.06 2 26-WEEK ANIMAL I;UMBER ------ Group.- I 105520 IOSS26 Group: 3 iossos IOSS23 Group: 4 105511 IOSS22 APPENDIX 4 Individual clinical Urinalysis Data Males Day 364 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPOI]IC ACID POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLGUS u PRO MO/DL -------- U GLU -------- U KET -------- U BILI -------- U BLOOD -------- UROBILI -------- Don* Level: 0 Dosage Unit: mg/kgiday 10 .... + 10 + + Dose Level: 0.15 0 + 10 Dose Lov*l: 0.75 10 10 + Dosage Unit: mg/kg/day ++ Dosage Unit: mo/ko/day ++ ANIMAL NUMBER ------ Group- I 105520 IOSS26 Group: 3 105505 105523 Group: 4 105511 105522 APPENDIX 4 individualclinicalurinalysisData Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS: T-629S) IN CYNOMOLGUS RSC PER HPP -------- WEC PER HPF -------- EPITH PER HPF -------- BACT PER HPF -------- CASTS PER LPF -------- CRYSTALS CRYSTALS PER LPF1 PER LPF2 -------- -------- URINE APPI ------- COMM ----- Dose Level: 0 Dosage unit: mg/kg/day 0 1 1 3 0 3BlE 1K BL 3BIK 0 BL Q 0 0 1 3 0 Dose Level: 0.15 DoSage Unit: mg/kg/day 0 0 0 1 1 1 2 3 0 0 3B3D 0 3B3D 0 BL - CK - Dose Level: 0.75 Dosage Unit: mg/kg/day 0 0 0 0 0 1 3 3 0 0 4B3D 0 3B 0 BK - BL - APPM4DIX 4 individual clinical Urinalysis Data Females Day 364 26-WEEK cApsULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLCUS ANIMAL NUt4BER ------ U VOL UL -------- SP GR -------- U PH -------- ACID Group: I Dose Level: 0 Dosage Unit: mg/kg/day 105529 105S49 166.0 1.011 8.0 ISO.0 1.011 8.0 S.D. 11 Group: 3 105539 IOSS52 158.0 11.31 2 1.011 .0000 2 Dose Level: O.lS 78.0 59.0 1.020 1.022 8.0 .00 2 Dosage Unit: mg/kg/day 7.0. 7.0 "P" S.D. t4 68.5 13.44 2 1.021 .0014 2 7.0 .00 2 Group: 4 Do$* Level; 0.75 Dosage Unit: mg/kg/day 105533 105542 43.0 1.018 6.5 109.0 1.019 7.5 KEAN S.D. N 76.0 46.67 2 1.018 .0007 2 7.0 .71 2 APPENDIX 4 individual Clinical Urinalysis Data Females Day 364 26-WEEK ANIMAL 14UMBER ------ CAPSULE TOXICITY STUDY WITH PERPLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLCUS u PRO U CLU U KET U BRLI U BLOOD UPOBrLr MG/DL -------- -------- -------- -------- -------- -------- Group: I IOSS29 105549 Group: 3 105539 IOSSc,2 Group: 4 105533 IOSS42 Dose Level: 0 0 + 0 + Dose Level: 0.15 10 10 + Dos* Level: O.IS 10 10 + Dosage Unit: mg/kg/day + + Dosage Unit: mg/kg!day + ++ ++ Dosage Unit: mg/kg/day ++ ++ + + JUIIKAL NU14BER ------ Group: I 105529 IOSS49 Group: 3 105539 105552 Group: 4 105533 105S42 APPENDIX 4 Individual clinical Urinalysio Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOL'RANE SULFONIC ACID POTASSIUM SALT (PFOS: T-6295) IN CYNOMOLOUS PSC PER HPF ---- --- WBC EPITH BACT PER HPF -------- PER HPF -------- PER HPF ------- CASTS CRYSTALS PER LPF -------- PER LPF1 ------ - CRYSTALS PER LPF2 -------- URINE APPI ------ Dose Level: 0 Dosage unit: mg/kg/day u 0 0 3 0 4B2D 3K BL 4BlD 0 BL (1 0 1 3 0 I)or.,L?evel: 0.15 Docage, unit: Wt!kg!day 0 0 1 3 0 4K 0 SK BL 0 0 1 3 0 3BID Dore Level: O.'IS Dosage unit: mg/ko/day 0 1 1 3 0 2B 0 BK 3B3K 0 BL 0 0 0 3 0 CONN ---- APPENDIX 4 individual Clinical Urinalyois Data Males Day 4S6 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS: T-62951 IN CYNOMOLGUS ANIMAL NUMBER ------ U VOL SP GR U PH ML -------- -------- -------- Group: 1 105520 105526 MEAN S.D. N Group: 3 Dose Level: 0 100.0 270.0 1.012 1.008 185.0 120.21 2 1.010 .0028 2 Dose Level: 0.15 Dosage unit: mo/ka/day 8.0 8.0 8.0 .00 .2 Dosage Unit- mo/ka/day 105505 105523 MEAN S.D. N Group: 4 105511 105522 MEAN S.D. N 286.0 78.0 1.004 1.011 282.0 147.09 2 1.008 .0050 2 Dose Level: 0.75 90.0 78.0 1.008 1.015 94.0 8.49 2 1.012 .0050 2 8.0 8.0 8.0 .00 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 APPENDIX 5 individual Anatomic Pathology Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS -------- ------------ -------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105508 SEX: MALE DOSE GROUPT 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIF TERMINAL BODY WRIGHT: 328 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 RECORDEFT: MICHELE ZIM DATE AND TIME OF NECROPSY: 02/25/99 10:24 PROSECTOR: KEVIN BILLINGS PATHOLOGISTT ROBERT LEEDLE WEIGHER: MICHELE ZINA P-O-S-T--F-I-X---WE-I-G-H-ER-:---N-(-Y-T-A-V-A-IL-A-B-L-E ------------------------------------------------------------------------------------- THE FOLLOWING ORCANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FH). NARROW, STERNUM (SE). BONE, STERNUM (SB). WE (BY), BRAIN (BR), KI HEART (HT), LIVER (LI). GALLBLADDER (GB), THYMUS (TH), LN, NESEWMRIC (MS), TRACHEA (TR). ESOPHAGUS (ES). THYROID (TY) , PARATHYROID (PT), ADRENAL, CORTEX (AC). ADRENAL, MEDULLA (KA). AORTA (AO). PITUITARY (PI). SALIV GL, HAMDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SH), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA). JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO). RECTUM (RE), SKIN (SK). MAMMARY, MAL.E (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYKIDES (EP), TESTIS ADIPOSE TISSUE (AT), t.N. TRACHBOBRON (TB), LN, ART NES/PANC (AP) THE FOLLOWING TZSSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: (BY), BRAIN (BR), HEART (HT), GALLBLADDI NARROW, FEMUR (FH), MARROW STERNUM (SE), DOME, STEMM (SB). EYE THYMUS (TH), ESOPHAGUS (ES;l THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE.). ILEUM (IL), CECUM (CE), RECTUM (RE). SKIN (SK), URINARY BLADD SEMINAL VESXCLES (SV). EPIDIDYKIDES (EP) TESTIS (TE) ---------------------------------------------------------------------------------------------------------------- 698 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONMS --------------------------------------------------------------------------------------------------- ANIMAL NUKBERT 105517 SEX: MALE STUDY DAY OF DEATH: DOSE GROUP: 1 SACRIFICE STATUS: 184 STUDY WEEK OF DEATH: 27 SCHEDULED, TERMINAL SACRIF TERMINAL BODY WEIGHT: 305 RECORDER: MICHELE ZINA DATE OF DEATH: 02/25/99 DATE AND TIME OF NECROPSY: 02/25/99 8:11 PROSECTOR: KEVIN BILLINGS WEIGHER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE ------------------------------------------------------------------------------------------------------------------ ORGAN NAME - ------------ ------- LEFT ADRENAL (ADO) RIGHT ADRENAL (ADl) BRAIN (BR) LF EPIDIDYMIS RT EPIDIDYMIS (EPO) (EPl) LF KIDNEY RT KIDNEY (KDO) (KD1) LIVER (LI) LP TESTIS (TEO) RT TESTIS (TEl) PANCREAS (PA) LF THYROID/PARA (TTO) RT THYROID/PARA (TTi) GALLBLADDER (GB) ABSOLUTE ORGAN WEIGHT (GRAMS) -------- .2840 .1430 62.4920 1.0930 1.2250 5.9980 5.7530 44.2710 8.0310 8.1690 5.8790 .1490 .1400 .6330 ORGAN WRIGHT RELATIVE TO BODY WEIGHT (t) -------- .0093 t .0047 t 2.0456 t .0359 t .0401 t .1963 t .1883 t 1.4491 % .2629 t .2674 t .1924 % .0049 t .0046 t ORGAN TO BRAIN WEIGHT RATIO -------- .0045 .0023 1.0000 .0175 .0196 .0960 .0921 .7084 .1285 .1307 .0941 .0024 .0022 0R STA ----- WEIG WEIG WEIGI WHIG WEI WHIG WEI WHIG WEI WEIG WEI WEI WEIG WEI -------B-I-L-E(-V-O-L-U-M-E-)----(D-I-)------------------1-.6-0-0-0- -m-L------------------------------------ ------------------------ 0BS 8RV AT 10N S . HISTOPATHOLOC;Y ---------------------------N-E-C-R-O-P-S-Y-----------------------------------------------------------------7---------- DOME, FEMUR (FE) : -GROWTH PLATE OPEN.-MODERATE NARROW, FEMUR (PH) : >SECTION EXAMINED; TISSUE MM PRESENT LUNG (LU) t -IFYPERPLASIA, LYMPHOCYTIC, PERIBRONCHIOLAR/ MINIMAL LIVER (LI) -INFILTRATE, LYMPHOHISTIOCYTIC.-MININAL, HU 699 APPENDIX 5 individual Anatomic Pathologry Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNONOtoGUS MONKEYS -------------------------------------------r--------------------------------------------------------------------- ANIMAL NUMBER: 105517 SEX: MALE DOSE GROUP: I SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH- 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WRIGHT: 30 RECORDER: MICHELE ZIM DATE AND TIME OF NECROPSY: 02125/99 POST-FIX WEIGHER: NOT AVAILABLE 8.-Il PROSECTOR: KEVIN BILLINGS PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZINA ----------------------------------------------------------------------------------------------------------------- 0 B S E R V A T 1 0 N S (CONTINUED) NECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- LN. NESMITERIC (MS) : -INFILTRATE,MACROPHAGE, PIGMENTED,-TMDERATE TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC.-SLIGHT ADRENAL. CORTEX (AC) t -HYPERTROPHY, CORTICAL CELL,-MINIMAL SALIV GL, MANDIB (SG) : -INFILTRATE. LYMPHOHISTIOCYTIC.-MININAL PANCREA,S (PA) : -INFILTRATE, LYMPHOHISTIOCYTIC,-NININAL COLON (CO) t -PARASITISM, XNTRAMU,SCULAR.-PRESENT GENERAL COMMENT (GC) -BONE NARROW SHEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - -- - - - - - -- - - - - - - - - - -- - - -- -- - - - - - - - - - - - 700 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 2 6-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULF'ONIC MONKEYS ---------------------------------------------- ------------ --------------------------------------------------- ANIMAL NUMBER: 105517 SEX: MALE STUDY DAY OF DEATH: DOSE 184 GROUP: 1 STUDY WEEK SACRIFICE OF DRATHT STATUS: 27 SCHEDULED, TERMINAL SACRI TERMINAL BODY WEIGHT: 30 RBMRDERT MICHELE ZIK DATE OF DEATH: 02/25/99 DATE AND TIME OF NECROPSY: 02/25/99 8:11 PROSECTOR: KEVIN BILLINGS WEIGHER: MICHELE Z114A PATHOLOGIST: ROBERT LEEDLE P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T--A-V-AI-L-A-B-LE-------------------------------------7--------------------------------------------- THE PBOOLNIED,WINFGEMURORGA(NFSE),WEMRAERROUWN,REMAFREK1A4BULRE (FMA)T, NKEACRRROOPWS,Y. STERNUM (SE), BONE STERNUM (SB), EYE (19Y), BRAIN (BR), KI LUNG (LU), HEART (HT), LIVER (LI). GALLBLADDER (08), SPLEEN (SP): THYMUS (TH), IN, NESENMIC (KS), TRAC ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC). ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG). MUSCLE, SKELETAL (SH), SPINAL CORD (SC). NERVE. SCIATIC (SN), STOMACH, GL l@ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLAM (CO). RECTUM SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR). SEMINAL VESICLES (SV). EPIDIDYNIDES TESTIS (TE). ADIPOSE TISSUE (AT), LN, TRACHROBROM (TS), LN, ANT 14ES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXRMINATIONs KIDM NARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), (KO), HEART (HT), GALLBLADDER (GB) SPLEEN (SP), THYMUS (TH), ESOPHAGUS (ES), THYROID (TY). PARATHYROID (PT), ADRENAL, MEDULLA (KA), AORTA ( PITUY,TARY (PI), MUSCLE, SKELETAL (SH). SPINAL CORD (SC). NERVE. SCIATIC (SN)* STOMACH, GL (ST). DUODENU14 JEJUNUM (JE) , ILEUM (IL). CBCU14 (CE). RECTU14 (RE), SKIN (SX), MAMMARY, MALE (MM). URINARY BLADDER (US). PROSTATE (PR), SEMINAL VESICLES (SV). EPIDIDYKIDES (HP), TESTIS (TE) -------------------------------------------------- -------------------------------------- ----------- 701 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLCUS MONKEYS ----------------------------------------------------------------------------------------------------------------- AN114AL NUMBER: 105519 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH- 27 TERMINAL BODY WEIGHTT 31 DATE AND TIME OF NECROPSY: 02/25/99 6t57 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ----------------------------------------------------------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0R ORGAN NAME ---------------------- (GRAMS) -------- TO 13ODY WEIGHT (t) -------- WEIGHT RATIO -------- ST ---- LEFT ADRENAL (ADO) RIGHT ADRENAL (ADl) BRAIN (BR) LF EPIDIDYNIS (EPO) RT EPIDIDYNIS (EPl) LF KIDNEY (KDO) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TEO) RT TESTIS (TEl) PANCREAS (PA) .2820 .2330 62.8980 .7730 .8270 5.5490 5.3860 53.1740 2.7700 2.9990 5.5570 .0090 t .0074 t 2.0031 t .0246 t .0263 t .1767 t .1715 t 1.6934 t .0885 % .0955 t .1770 % .0045 .0037 1.0000 .0123 .0131 .0882 .0956 .8454 .0442 .0477 .0883 WEIG WEI WHIG WHIG WEIG WEI WEI WEI WEIG WHIG WEIG LF THYROID/PARA (TTO) RT THYROID/PARA (TT1) GALLBLADDER (GB) .1310 .1220 .7260 .0042 % .0039 t .0021 .0019 WEI WEIG WEIG BXLE(VOLUME) (BI) 1.2000 mL -------------------------------------------------------------------------------------------------------------- 0B SBRV AT 10N S NECROPSY ----------------------------------------------------------------------------------- HISTOPATHOLOGY ---------------- BONS. FEMUR (FE) : -GROWTH PLATE OPEN.-HODERATZLY SEVERE NARROW, FEMUR (PH) >SECTION RXAMINED; BRAIN (SR) i TISSUE NOr PRESENT -INFILTRATE, MACROPRAGES, KIDNEY (KD) i PIGMENTED, PERIVAI -INFILTRATE, LYMPHOHISTIOCYTIC,-NIN114AL 702 26-WEEK ANIMAL tiUMBER ------- Group: I 105520 105526 Group: 3 105505 iOSS21 Group: 4 iossii iOSS22 APPENDIX 4 individual Clinical Urinalysin Data Males Day 456 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS U PRO -M-G-/D-L --- U GLU U KET U BILI U BLOOD -------- -------- -------- -- ----- UROBILI -------- Dose'Level: 0 Dosage Unit: mo/ko/day 0 0 Dose Level: 0.15 Dosage Unit: mg/kg/day 0 10 Dose Level: 0.75 Dosage unit: mg/kg/day 0 0 ANIMAL NUMBER ------ Group: I 105S20 105526 Group: 3 105sos IOSS23 Group: 4 105511 105522 APPENDIX 4 individual Clinical Urinalysis Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT IPPOS; T-629S) IN CYNOMOLGUS PJBC WBC PER HPF PER HPF -------- -------- EPITH PER HPF -------- BACT PER HPF -------- CASTS P-E-R--L-P-Fr - CRYSTALS CRYSTALS URINE COMM PER LPFI PER LPF2 APPI -------- -------- -------- ----- Dose Level: 0 Dosage Unit: M/kg/day 0 0 0 3 0 lBlD 0 0 0 1 3 0 0 0 Doae Level: 0.15 Dosage llnit: mo/ka/day 0 0 0 2 0 0 0 0 0 0 3 0 4BlD 0 Dose Level: 0.7S Dosage Unit: mg/kg.1day 0 0 1 3 0 0 0 0 0 0 3 0 2B4D 0 BK AJ AJ BK Bi Q si kppm4DIX 4 individual clinical Urinalysis Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULPONIC POTASSIUM SALT (PFOS; T-6295) IN CYIIOHOLGUS ANIMAL IIUMBER ------ U VOL SP GR U PH ML -------- -------- -------- ACID Group: 1 105529 105549 HEAN . S.D N Group: 3 105539 IOSS52 KEAN S.D. N Group: 4 105533 105542 MEAN S.D. N Dose Level: 0 98.0 330.0 1.013 1.005 214.0 164.05 2 1.009 .0057 2 Dose Level: 0.15 198.0 92.0 1.008 1.014 145.0 74.95 2 1.011 .0042 2 Dose Level: 0.75 60.0 176.0 1.002 1.008 118.0 82.02 2 1.005 .0042 2 Dosage Unit: mg/ka/day 8.0 8.0 8.0 .00 2 Dosage Unit: mg/kg/day 7.5 9.0 7.8 .35 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 26-WEEK ANlt4AL NUMBER ------ Group: I 105529 105549 Group: 3 IOSS39 IOSSS2 Group: 4 105533 105542 APPENDIX 4 individual clinical Urinalysis Data Females Day 456 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-629S) IN CYNOMOLCUS u PRO 14G/DL -------- U CLU -------- U KET -------- U BILI -------- U SE.QOD -------- UROBILI -------- Dose Level: 0 Dosage Unit: mg/kg/day 0 10 Dose Level: O.IS Dosage Unit- mg/),g/d.@y 0 0 Dose Level: 0.75 Dosage Unit: mg/ka/day 0 0 + ANIMAL NUMBER ------ Group. 1 IOSS29 iOSS49 Group: 3 105539 105552 Group: 4 TOSS33 iOSS42 APPENDIX 4 individual Clinical Urinalysis Data Females Day 4SG 26-WEEK CAPSULE TOXICITY STUDY WITti PERFLUOROOCTANE SULFOI;IC ACID POTASSIUM SALT IPFOS: T-6295) IN CYNOMOLGUS RBC PER HPF -------- WBC PER HPF -------- EPITH PER HPF -------- BACT PER HPF -------- CASTS CRYSTALS PER LPF PER LPF1 -------- ------- CRYSTALS URINE PER LPF2 APP1 -------- -------- COMM ----- Dose Level: 0 Dosage Unit: mg/kg/day 0 0 1 3 0 2B4D 0 0 1 1 3 0 0 0 Dose Level: O.lS Dosage Unit: mg/kg/day 00 10 11 33 00 03B 00 Dose Level: 0.75 Dosage Unit: mg/kg/day 00 00 10 33 00 24BB 00 EK AJ AJ - BK - AX - AL - APPENDIX 4 individual Clinical urinalysis Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS: T-6295) IN CYNO14OLGUS ANIMAL NUMBER ------ r.roup- I 105520 105526 MEAN S.D. N Group: 3 105505 ZOSS23 MEAN S.D. Group: 4 105511 105522 HEM S.D. N U VOL ML -------- SP GR -------- U PH -------- Dose Level: 0 Dosage Unit: mo/ka/day 480.0 1.005 8.0 380.0 1.005 8.0 430.0 70.71 2 1.005 .0000 2 8.0 .00 2 Dose Level: 0.15 Dosage unit.- mg/kg/day 405.0 1.004 7.S 195.0 1.008 8.0 300.0 148.49 2 1.006 .0028 2 7.8 .35 2 Dose Level: 0.75 Dosage Unit: mg/kg/day 345.0 1.005 8.0 100.0 1.015 8.0 222.S 173.24 2 1.010 .0071 2 8.0 .00 2 3H APPENDIX 4 Individual clinical Urinalysis Data males Day 546 26-WEEK ANIMAL NUMBER -----Croup: 1 CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLOUS u PRO U GLU U KET U BILI U BLOOD UROBILI MG/DL -------- -------- -------- - ------ ------- -------- Doso Level: 0 Dosage unit: mg/ko/day 105520 105526 Group: 3 0 0 Dose Level: 0.15 Dosage Unit: mg!kg/day 105505 ZOSS23 Group: 4 105511 IOSS22 0 0 Dose Level: 0.7S @o 0 Dosage Unit: mg/kg/day ANIMAL NUMBER ------ GroUp: I 105520 105526 Group- 3 lossos IOSS23 Group: 4 iossii IOSS22 APPENDIX 4 3 Individual Clinical Urinalysis Data Males Day 546 26-WEEK CAPSULE WXXCITY-ST(JDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RSC PER HPP -------- WBC PER HPF -------- EPITH PER HPF -------- BACT PER HPF -------- CASTS PER LPF -------- CRYSTALS PER LPFI -------- CRYSTALS PER LPF2 -------- URINE APPI -------- COMMENT ------- Dose Level: 0 Dosage Unit: mg/kglday 0 0 1 1 0 IB 0 AJ 0 0 0 3 0 1B 0 Ai Q Dose Levelt 0.15 Dosage Unit: mg!kg!day 0 0 0 2 0 0 0 0 0 0 1 0 2B 0 AJ AJ Q Dose Level: 0.75 Dosage Unit: mg/ka/day 0 0 0 1 0 1B 0 Ai Q 0 0 0 1 0 2BlD 2E BK APPENDIX 4 3 individual clinical Urinalysis Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAIIE SULPONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNO@IOLCUS ANIMAL NUMBER ------ U VOL SP CR U PH t4L -------- -------- -------- Group: I IOSS29 IOSS49 Dose Level: 0 105.0 160.0 1.015 1.007 Dosage Unit: mg!kg/day 9.0 9.0 MEAN S.D. if Group: 3 iOSS39 105552 MEAN S.D. N Group: 4 132.5 38.89 2 1.011 .0057 2 Dose Level: 0.15 85.0 SO.0 1.017 1.019 67.5 24.75 2 1.018 .0014 2 Dose Level: 0.75 8.0 .00 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Dosage Unit: mg/kg/day 105533 IOSS42 42.0 2.017 8.0 156.0 1.010 8.0 MEAN S.D. N 99.0 80.61 2 1.014 .0050 2 8.0 .00 2 APPENDIX 4 3 Individual clinical Urinalysis Data Females Day 546 26-WEEK ANIMAL NUMBER ------ C"SULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID poTAssiUM SALT (PFOS; T-6295) III CYNOMOLCUS u PRO MG/DL -------- U GLU -------- U KET -------- U BILI -------- U BLOOD -------- UROBILI -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day ZOSS29 105549 Group: 3 0 0 Dose Level: 0.15 Dosage Unit: mg/kg./day IOSS39 105552 Group: 4 10 10 Dose Level: 0.75 Dosage Unit: mg/kg/day 105533 0 105542 0 +*+ ANIMAL NUMBER ------ Group: I 105529 iO5S49 Group: 3 105539 105552 Group.- 4 iOSS33 105542 APPENDIX 4 3 individual Clinical Urinalysis Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC POTASSIUM SALT IPFOS;.T-6295) IN CYNOMOLGUS ACID RBC PER HPF -------- k= EPITH PER HPF PER HPF -------- ------- BACT PER HPF --- ---- CASTS CRYSTALS PER LPF PER LPFI -------- -------- CRYSTALS PER LPF2 -------- URINE APP1 -------- COMMENT ------- Dose Level: 0 Dosage Unit: mg/ko/day 0 1 0 2 0 2B2D IF Bi - - 0 0 0 2 0 2B 0 Bi Dose Level: 0.15 Dosage Unit: mg;kg/day 00 00 00 22 00 32B821EB 00 BK - BL - Dose Level: 0.75 Dozag* Unit: mg/kg/day 0 0 0 2 0 3B3D 0 0 1 1 1 0 3B 0 EL - AL - Ccyvance6329-223 3M T-6295.7 AIPPFNDIX 5 individuaPlalmiwyl CoA Oxidase Deteminations IndividualAnatoniicPathologyData 685 Appendix 5 individual Palmitoyl CoA oxidase Determinations Terminal Sacrifice Males 26-WEEK CAPSULE TOXICITY STUDY WITH PERFT.UOROOCTANE SULPONIC POTASSIUM SALT (PFOS; T-6295) IN CYN0140EGUS MONKEYS ANIMAL NUMBER ------ PCOAO IU/0 -------- ACID Group: 1 105508 105517 105519 105527 MEAN S.D. N Group: 2 105514 105515 IOSS16 105521 MEAN S.D. N Group: 3 105510 105518 105524 105528 MEAN S.D. N Dose Level: 0 4 4 6 7 5 1.5 4 Dose Levels 0.03 4 5 4 6 5 1.0 4 Dose Levels 0.15 6 6 5 5 6 .6 4 Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day 686 Appendix 5 individual Palmitoyl COA 6xidase Determinations Terminal sacrifice Males 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ACID ANIMAL NUMBER ------ Group: 4 105507 105512 MEAN S.D. N PCOAO IU/G -------- Dose Level: 0.75 8 6 7 1.4 2 Dosage Unit: mg/kg/day 687 Appendix 5 individual Palaitoyl CoA oxidase Determinations Terminal Sacrifice Females 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULFONIC ACID MONKEYS ANIMAL NUMBER ------ PCOAO IU/G -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day 105530 3 105531 4 105535 4 105544 5 MEAN S.D. N Group: 2 Dose 4 8 4* Level: 0.03 Dosage Unit: mg/kg/day 105537 105541 105547 105550 MEAN S.D. N Group: 3 4 4 2 5 4 1.3 4 Dose Levelt 0.15 Dosage Unit- mg/kg/day 105532 5 105538 5 105545 6 105548 7 KEAN 6 S.D. 1.0 N 4 688 Appendix 5 individual Palmitoyl coA oxidase Determinations Terminal Sacrifice Females 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS SULPONIC ACID MONKEYS ANIMAL NUMBER ------ Group: 4 105534 105536 105540 iosssi PCOAO IU/G -------- Dose Level: 0.75 6 7 6 5 Dosage Unitt mg/kg/day MEAN 6 S.D. N 689 APPENDIX 5 Individual Anatomic Pathology Data unscheduled Deaths 26-WEEK CAPSULE TOXICITY STUDY WITH PEITFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLOGUS MONKEYS ------------------------------------------------------------------------------------------------------------ ANI14AL NUMBER: 105506 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: UNSCHEDULED (M) TERMINAL BODY WEIGHT.- 362 DATE OF DEATH: 02/20/99 STUDY DAY OF DEATH: 179- STUDY WEEK OF DEATH: 26 RECORDER: NANCY DIEDRI DATE AND TIME OF NECROPSY: 02/20/99 12:40 PROSECTOR: DAVID SCHUETTE . PATHOLOGIST: ROBERT LEEDLE WEIGHER: NANCY DIEDRI P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T--A-VA-I-L-A-BL-E--------------------------------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0R ORGAN NAME (GRAMS) -------- TO BODY WEIGHT (t) -------- WRIGHT RATIO -------- ST ---- ---------------------- LEFT ADRENAL (ADO) .4730 .0130 t .0106 t .0072 .0058 WEI WEIG RIGHT ADRENAL BRAIN (BR). (ADl) .3040 65.9350 1.8189 t .0352 % 1.0000 .0194 WEIG WEI LF EPIDIDYMIS (EPO) 1.2760 1.2520 .0345 t .0190 WEIG RT EPIDIDYNIS (EPl) LP KIDNEY (KDO) 6.1230 5.9240 .1689 % .1634 % .0929 WEI .0898 WEI RT KIDNEY (KDI) LIVER (LI) 88.6340 2.4451 % 1.3443 WEI LP TESTIS RT TESTIS (TEO) (TEI) 7.0730 7.0020 .1951 % .1932 t .1849 % .1073 .1062 .1016 WRIC WEIG WEIG PANCREAS (PA) LF THYROID/PARA (TTO) 6.7010 .1980 .2070 .0055 t .0057 % .0030 WEI .0031 WEI RT THYROID/PARA (TT1) -------- -------- Nor GALLBLADDER (GB) -------- -------- NOT -------B-I-LE-(-V-O-LU-M-E-)-----(-B-I-)----------------------------------------------------------------------------------------- 0 8 S 8 R V A T 10 N S NECROPSY ------------------------------------------------------------ HISTOPATHOLOGY ------ --------------------------------------- BORE, FEMUR (FE) : -GROWTH PLATE OPICN,-MODERATELY SEVERE BRAIN (BR) i -INFILTRATE. LYMPHOHISTIOCYTIC, PERIVASCULAR -INFILTRATE, -INFILTRATE, MACROPHAGES, PIGMENTED, PERIVA LYMPHOHISTIOCYTIC, MMINGEKL. -S KIDNEY (KD) : -INFILTRATE. LY14PHOHISTIOCYTIC.-MINIMhL -CAST, PROTRINACROUS,-SLIGHT 690 APPENDIX 5 individual Anatomic Pathology Data Unscheduled Deaths 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLOUS MONKEYS -------------------------------------------------------------------------------------- -------------------------- ANIMAL NUMBER: 105506 SEX. MALE DOSE GROUP: 4 SACRIFICE STATUS: UNSCHEDULED (M) STUDY WEEK OF DEATH: 26 TERMINAL BODY WEIGHT: 362 DATE OF DEATH: 02/20/99 STUDY DAY OF DEATH: 179 PROSECTOR: DAVID SCHUETTE RBCOP43ER: NANCY DIEDRI WEIGHER: NANCY DIEDRI DATE AND TIME OF NECROPSY: 02/20/99 12:40 POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE --------------------- -------- ------------------------------------------------------------------------------- 0 B S B R V A T 1 0 N S (CONTINUED) HISTOPATHOLOGY NECROPSY ----------------------------------------------- ---------------------------------------------------------------- LIVER (LI) : -INFILTRATE. LY14PHOHISTIOCYTIC.-MINIKRL, MULI -HYPERTROPHY, HEPATOCELLVLAR.-HODERATE. -STASIS, BILE,-SLIGHT, MULTI-FOCAL DIPPI THYMUS (TH) -CYST.-PRESENT -ATROPHY.-MODERATELY SEVERE TRACHEA (TR) : -INFILTRATE. LYMPHOHISTIOCYTIC.-MININAL ESOPHAGUS (ES) i -INFILTRATE, LYMPHOHISTIOCYTIC.-SLIGHT THYROID (TY) t -INFILT,RATE, LYMPHOHISTIOCYTIC,-SLIGHT -CYST ULTIMOBRAWHIAL, -PRESENT ADRENAL, CORTEX (AC) : -MINERALIZATION, VASCULAR,-MnnKAL SALIV GL, KRNDIB (SG) i -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT SPINAL CORD (SC) : -INFILTRATION. LYMPHOHISTIOCYTIC MENINGRAL/ SLIGHT DUODENUM (DU) -INFILTRATE, MACROPHAGE, PIGMENTED.-MODERATE JEJUNUM (JE) : -INFILTRATE, MACROPHAGE, ILEUM (IL) : PIGKMTED.-SLIGHT -INFILTRATE, MACROPHAGE, PIGHEMD,-SLIGHT URINARY BLADDER (UB) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT 691 APPENDIX 5 individual Anatomic Pathology Data Unscheduled Deaths 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS---M-O-NK-E-Y-S------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105506 DATE OF DEATH: 02/20/99 SEX: MALE STUDY DAY OF DATE AND TIME OF NMROPSY-. 02/20/99 12:40 POST-FIX WEIGHER: NOT AVAILABLE DOSE GROUP: 4 SACRIFICE DEATH: 179 STUDY WEEK OF DEATH: PROSECTOR: DAVID SCHUETTE PATHOLOGIST: ROBERT LEEDLE STATUS-. 26 UNSCHEDULED (M) TERMINAL BODY WRIGHT: 36 RECORDER: NANCY DIRDE WEIOHBR-. NANCY DIEDRI ---------------------------------------------------------------------------------7------------------------------- 0 B S E R V A T 1 0 N S (CONTINUED) NECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- CAUSE OF DEATH (CD) : -UNDETER14INED,-PRESENT GENERAL COMMENT (GC) -BONE MARROW SHEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS -- - - - - - - - -- -- - - - - - - - - - - - - - - ----------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: DOME, FEMUR (FE), t4ARRON, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB). EYE (BY). BRAIN (BR), KI LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP). THY14US (TH), LN, NESENTERIC (NS), TRAC ESOPHAGUS (ES), TFIYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (NA), AORTA (AO). PITUITARY (PI), SALIV GL, MANDIB (SG). MUSCLE, SKELETAL (SM). SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DO), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE). COLON (CO), RECTUM SKIN (SK), MAMMARY. MALE (MM), URINARY BLADDER (UB), PROSTATE (PR). SEMINAL VESICLES (SV). SPIDIDYKIDES TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEODRON (TE), LN, ANT NES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, FEMUR (FH) , KARROW, STERNUM (SE), BONE, STERNUM (SB). EYE (EY). LUNG (LU), HEART (HT), GALLBLADD SPLEEN (SP). LN, 14ESENTERIC (MS), PARATHYROID (PT). ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI) MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN). STOMACH, GL (ST). PANCREAS (PA), CECUM (CE). COLON (CO), SKIN (SK), MAMMARY, KHLE (MM), PROSTATE (PR), SEMINAL VESICLES (SV), SPIDIDYKIDES (EP), TESTIS (TH) ---------------------------------------------------------------------------------------------------------------- 692 APPENDIX 5 individual Anatomic Pathology Data Unscheduled Deaths 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105509 SEX.- MALE STUDY DAY OF DEATH: DOSE GROUP: 4 SACRIFICE STATUS: 155 STUDY WEEK OF DEATH: 23 UNSCHEDULED (D) TERMINAL BODY WEIGHT: RECORDER: MICHELE NOT ZINA DATE OF DEATH: 01/27/99 PROSECTOR: NANCY DIEDRICH DATE AND TIME OF NECROPSY: 01/27/99 10:21 PATHOLOGIST: ROBERT LEEDLE WEIGHER: NOT AVAILABLE P-O-S-T--F-I-X---WE-I-G-H-ER-:---N-O-T--A-V-AI-L-A-B-LE-------------------------------------------------------- ---------------------------- *** ORGAN WEIGHTS WERE NOT RECORDED *** ----------------------------------------------------------------------------------------------------------------- 0B SE RV NECROPSY -------------------------------------------------------------- AT 10N S HISTOPATHOLOGY ---------------------------------- ------------ BONE, FEMUR (FE) -. -GROWTH PLATE OPEN,-MODERATELY MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT SEVERE PRESENT KIDNEY (KD) : .-MINERALIZATION, PAPILLARY,-MODERATE LUNG (LU) -ADHESION(S); ALL L013ES TO EACH OTHER AND PLEURA: MULTIPLE INDISTINCT ADHESIONS; CANNOT DISTINGUISH LOBES FROM ONE ANOTHER; COLLECTED -MOTTLED; ALL RIGHT ROBES: RED, DARK RED, AND TAN; LOBES APPEAR FIRM -EROSION (S) /ULCERATION (. S); APPEARS TO BE RIGHT CAUDAL LOBE: SINGLE ULCERATED AREA 2.5 x 1.5 CM; ULCERATED AREA EXTENDS DEEP INTO LUNG TISSUIE; WALLS OF ULCERATION APPEAR GREEN, TAN, GRAY AND MOIST; COLLECTED INTACT LIVER (LI) : -MOTTLED; ALL LOBES: DARK BROWN AND TAN -LARGE; ALL LOBES: THICKENED LUNG (LU) : -FIBROSIS, PLEURAL/SUBPLEURAL,-MODERATE -INFILTRATE, MACROPliAGE, ALVEOLAR,-MODERATE -NECROSIS.-SEVERE -INFLAMMATION, ACUTE,-SEVERE -FIBRIN, PLEURAL,-MODERATELY SEVERE LIVER (LI) -HYPERTROPHY, HEPATOCELLULAR,-SLIGHT, DIFFUSE -VACUOLATION, HEPATOCELLULAR, CENTRILOBULAR,- THYMUS (TH) : -ATROPHY,-MODERATE TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,7MINIMAL SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL 693 APPENDIX 5 Individual Anatomic Pathology Data .Unscheduled Deaths 26-WEgK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------7 --------------------------------------------------------------------- ANIMAL NUMBER: 105509 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: UNSCHEDULED (D) DATE OF DEATH: 01127/99 STUDY DAY OF DEATH: 155 STUDY WEEK OF DEATH: 23 TERMINAL BODY WEIGHT: NOT DATE AND TIME OF NECROPSY: 01/27/99 10:21 PROSECTOR: NANCY DIEDRICH RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: NOT AVAILABLE ------------------------------------------------------------------------------------------------------------------- 0 B S E R V A T 1 0 N S (CONTINUED) NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------------------------------------------------------- JEJ_UNUH (JE) : INFILTRATE, HACROPRAGE, ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGHENTED,-MODERATE PIGMENTED,-SLIGHT COLON (CO) -DARK FOCUS(I)/AREA(S); WITHIN HUCOSA: SINGLE DARK BROWN COLON (CO) : >UNREMARKABLE AREA, 0.3 x 0.2 CH; COLLECTED ON ROUTINE SECTION CAUSE OF DEATH (CD) -NECROSIS, PULMONARY,-PRESENT LN, TRACHEOBRON (TE) LN, TRACHEOBRON (TB) : -LARGE; UP TO 1.0 X 0. 9 X 0.5 CM (CAP 29) -INFLAMMATION, ACUTE,-MODERATE - - - - - - - - - --- - - - - - - - - - - - - - - - - - - - - - - - - - - 694 APPENDIX 5 Individual Jknatomic Pathology Data Unscheduled Deaths 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: 105509 DATE OF DEATH: 01/27/99 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: UNSCHEDULED (D) STUDY DAY OF DEATH: 155 STUDY WEEK OF DEATH: 23 TERMINAL BODY WEIGHT: NOT DATE AND TIME OF NECROPSY: 01/27/99 10:21 PROSECTOR: NANCY DIEDRICH RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVA3:LABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: NOT AVAILABLE -------------------------------------------------------------------------- ---------------------------------------;-- THE FOLLOWING ORGANS WERE UNRE14ARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW,. FEMUR (FH), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNLR HEART (HT), GALLBTADDER (GE), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC THYROID (TY), PAP.ATHYROID (PT), ADRENAL, 'CORTEX (AC), ADRENAL, MEDULLA SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, (MS), TRACHEA (TR), ESOPHAGUS (ES) (MA), AORTA (AO), PITUITARY (PI), SCIATIC (SN). STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (,TE), ILEUM (IL), CECUM (CE), RECTUM (RE), SKIN (SK), MAMMARY, MALE URINARY BLADDER (UB). PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE GENERAL COMMENT (GC), IN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (L-Y), BRAIN (BR), HEART- (HT). GALLBLADDER (GB), SPLEEN (SP). LN, MESENTERIC (14S), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE. SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), CECUM (CE), RECTUM (RE), SKIN (SX), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR) , SEMINAL VESICLES (SV) , EPIDIDYMIDES (EP) . TESTIS (TE) ------------------------------------------------------------------------------------------------ ------------- 695 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOHOLGUS MONKEYS -------------------------------------------------------------------------------------------------------------------- ANI14AL NUMBER: 105508 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERHINHL SACRIFIC DATE OF DEATH: 02/25/99 DATE AND TIME OF NECROPSY: STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 02/25/99 10.-24 PROSECTOR: KEVIN BILLINGS TERMINAL BODY WEIGHT: 3285. RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA -------------------------------------------------------------------------------------------------------------------- ORGAN NAME ---------------------- LEFT ADRENAL (ADO) RIGHT ADRENAL BRAIN (BR) (ADl) LF EPIDIDYMIS RT EPIDIDYMIS (EPO) (EPl) LF KIDNEY (KDO) RT KIDNEY (KDI) LIVER (LI) LF TESTIS RT TESTIS PANCREAS (TEO) (TEI) (PA) LF THYROrD/PARA (TTO) RT THYROID/PARA (TT1) GALLBLADDER (GB) ABSOLUTE ORGAN WEIGHT (GRAMS@ -------- .2650 .2010 62.3670 .8310. 1.0370 5.8660 5.4930 59.3880 5.5360 5.1190 4.3000 .1520 .1390 .4890 ORGAN WEIGHT RELATIVE TO BODY WEIGHT -------- .0081 % .0061 % 1.8985 t .0253 % .0316 % .1786 % .1672 % 1.8079 % .1685 % .1558 % .1309 % .0046 % .0042 t ORGAN TO BRAIN WEIGHT RATIO -------- .0042 .0032 1.0000 .0133 .0166 .0941 .0881 .9522 .0988 .0821 .0689 .0024 .0022 0RG ST AT ------- WEIGHT WEIGHT WEIGHT WEIGHT WEIGHT WEIGHT WEIGHT WEIGHT WEIGHT WEIGHT WEIGHT WEIGHT WEIGHT WEIGHT BILE(VOLUME) (BI) 1.6000 mL ------------------------------------------------------------------------------------------------------------------- 0B S ERV AT 1 0N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------------------------------------------------------- BONE, FEMUR (FE) : -GROWTH PLATE OPEN.-MODERATELY SEVERE KIDNEY (KD) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT -GLOMERULOSCLEROSIS,-MINIMAL LUNG (LU) -RED FOCUS (I) /AREA(S); FOCI ALL LOBES: 14ULTIPLE DARK RED PINPOINT LUNG (LU) : -HYPERPLASIA, SLIGHT LIVER (LI) -INFILTRATE, LYMPHOCYTIC, PERIBRONCHIOLAR/PER LYMPHOHISTIOCYTIC,-MINIMAL, MULTI 696 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE'SULOONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------7 - ANIMAL NUMBER: 105508 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIF DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 328 DATE AND TIME OF NECROPSY: 02/25/99 10:24 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ------------------------------------------------ ------------------------------------------------------ 0 B S E R V A T 1 0 N S (CONTINUED) NECROPSY HISTOPATHOLOGY --------------------------------------------------------------------------------------------------------------- SPLEEN (SP) : -LARGE; 7.0 X 4.0 X 3.0 CM SPLEEN (SP) : >UNREMARKABLE LN, MESENTERIC (MS) -HEMORRHAGE,-SLIGHT TRACHEA (TR) - -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT SALIV GL, MANDIB (SG) :. -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT COLON (CO) : -INFILTRATE, ROSINOPHILIC,-SLIGHT MAMMARY, MALE (MM) : >SECTION EXAMINED; TISSUE NOT PRESENT PROSTATE (PR) : -INFLAMMATION, LYMPHOHISTIOCYTIC.-MINIMAL GENERAL COMMENT (GC) -BONE MARROW SMEAR TAKEN - -E-YES- DAVIDSONS --- - - - - - - - - - - - - -- - - - - - - - - - - - - - - - - - - 697 APPENDIX 5 C(A Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTME SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------- ------------------------------------------------------------------------------------------ ANIMAL NUMBER: 105508 SEX: KnE DOSE GROUP: I SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE TER14INAL BODY WEIGHT3 3285.0 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH. 27 RECORDER-. MICHELE ZINK DATE AND TIME OF NECROPSY: 02/25/99 10:24 PROSECTOR: KEVIN BILLINGS WEIGHER: MICHELE ZIKA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE ------------------------- --------------------------------------------------------------- -------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NBCROPSY: (EY). BRAIN (BR), KIDURY BONE, FEMUR (FE), NARROW. FEMUR (FK), NARROW, STERNUM (SE), BONE, STERNUM (SB), EYE HEART (HT), LIVER (LI), GALLBLADDER (GS). THYMUS (TH). LM, NESENTERIC (MS), TRACM (TR). ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC). ADRENAL, MEDULLA (MA), AORTA (AO). PITUITARY (PI), SALIV GL, HANDIS (SG), MUSCLE, SKELETAL (SI4), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA). JEJUNUM (JE). ILEU14 (IL). CEM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (U]3), PROSTATE (PR). SEMINAL VESICLES (SV). EPIDIDYKIDES (EP), TESTIS (TE) ADIPOSE TISSUE (AT), t.N, TRACHROBRON (TB), LN, ANT NES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC RXAHIHATIONs MARRON, PM4UR (FM), NARROW. STERNUM (SE), DONE, STERNUM (SB), EYE (EY), BRAIN (BR). HEART (HT), GALLBLADDER THYMUS (TH), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (14A). AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CRCUM (CE), RECTUM IRE), SKIN (SK), URINARY BLADDER SEMINAL VESICLES (SV). EPIDIDYKIDES (EP), TESTIS (TH) ---------------------------------------------------------------------------------------- ------------------------- 698 APPENDIX 5 cov, Individual Anatomic Pathology Data Terminal Sacrifice .PA 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAM SULPONIC ACID POTASSIUM SALT (PFOSsT-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105517 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 3055.0 G DATE OF DEATHT 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 RECORDER: MICHELE ZINA DATE AND TIME OF NECROPSY: 02/25/99 8-.11 PROSECTOR: KEVIN BILLINGS WEIGHER: MICHELE ZIKA P-O-S-T--F-I-X--W-E-IG-H-E-R:---N-OT--A-V-A-IL-A-B-LE---------------------P-A-TH-O-L-OG-I-S-T:---R-O-BE-R-T--L-E-ED-L-E------------------------------------------------ ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0 RGAb ORGAN MAKE (GRAMS) TO BODY WEIGHT (t) -------- WEIGHT RATIO -------- STA TU --------- ---------------------- -------.2840 .0093 % 0045 WEIGHT LETT ADRENAL (ADO) RIGHT ADRENAL (ADI) BRAIN (BR) 1430 62.4920 .0047 t 2.0456 % .0358 % :0023 1 0000 :0175 WRIGHT WEIGHT WRIGHT LF EPIDIDYNIS (EPO) 1.0930 1.2250 .0401 % 0196 WRIGHT RT EPIDIDYMIS (EPl) LF KIDNEY (KDO) RT KIDNEY (KD1) 5.9980 5.7530 44.2710 .1963 % .1883 % 1.4491 % :0960 .0921 .7084 WEIGHT WRIGHT WRIGHT LIVER (LI) LP TESTIS (TEO) RT TESTIS (TEI) 8.0310 8.1690 5.8790 .2629 % .2674 % .1924 % .1285 .1307 .0941 WEIGHT WEIGHT WEIGHT PANCREAS (PA) LP THYROID/PARA RT THYROID/PARA (TTO) (TTI) .1490 .1400 .0049 % .0046 % .0024 .0022 WEIGHT WEIGHT WRIGHT GALLBLADDER (GB) .6330 ------B-I-L-E-(-V-O-L-UM-E-)---(-B-I-)---------------1-.6-0-0-0--mL------------------------------------------------------------------------- 0B SBR VAT 10N S . HISTOPATHOLOGY ---------------------------N-E-C-R-O-P-S-Y------------------------------------------------------------7-----------------BONE, FEMUR (FE) -GROWTH PLATE OPEN,-140DERATE NARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT LUNG (LU) : -HYPERPLASIA, LYMPHOCYTIC. PERIBROUCHIOtAR/PERIV) MINIMAL LIVER (LI) -INFILTRATE, LYMPHOHISTIOCYTIC,-MIN114AL, MULTZ-F 699 APPENDIX 5 c individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULP)MIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNONOEOGUS MONKEYS --------------------------------------------------------------------- -------------------------------------------7--- ANIMAL NUMBER: 105517 SEX: 14ALE DOSE GROUPs I SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3055.0 RECORDER: MICHELE ZIKH DATE AND TIME OP NECROPSY: 02/25/99 8:11 PROSECTOR: KEVIN BILLINGS PATHOLOGIST. ROBERT LEEDLE WEIGHER: MICHELE Z114A P-O-S-T--F-I-X--W-E-I-G-HE-R-:---N-M---A-VA-I-L-AB-L-E---------------------------------------------------------------------------- ------------- 0 B S B R V A T 1 0 N S (CONTINUED) NECROPSY HISTOPATHOLO(;Y --------------------------------------------------- ---------------------------------------------------------------- LN, HESENTERIC (NS) : -INFILTRATE, 14ACROPHAGE. PIGMENTED,-MODERATE TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT ADRENAL, CORTEX (AC) s -HYPERTROPHY, CORTICAL CELL.-MINIUAL SALIV GL, KANDIB (SG) : -INFILTRATE, LYt4PHOHISTIOCYTIC,-MININAL PANCREAS (PA) : -INFILTRATE, LYMPHOHISTIOCYTIC.-MININAL COLON (CO) : -PARASITISM, INTRAMU,SCULAR,-PRESENT GENERAL COMMENT (GC) -BONE HARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS 700 APPENDIX S c Individual Anatomic Pathology Data Terminal Sacrifice 2 6-WEEK CAPSULE TOXICITY STUDY WITH PE"LUOROOCTANE SULFOUIC ACID POTASSIUM SALT (PFOS;T-629S) IN CYNOMOLGUS MONKEYS-------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBERT 105517 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WRIGMs 3055.0 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 RECORDER: MICHELE ZINK DATE AND TIME OF NECROPSY: 02/25/99 8:11 PROSECTOR: KEVIN BILLINGS PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZINA P-O-S-T--F-I-X---W-EI-G-H-ER-:---N-O-T--A-V-AI-L-A-B-LE------------------------------------!------------------------------------- ----------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), NARROW, STERNUM (SE), BONE, STERNUM (SB), RYE (BY). BRAIN (SR), KIVU" LUNG (LU). HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP). THYMUS (TH), IM, NESENTERIC (US). TRACHEA ESOPHAGUS (ES), THYROID (TY), PARATHYROID.(PT), ADRENAL, PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUMN CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), (SH). SPINAL CORD (SC). NERVE, SCIATIC (SH). (JE), ILEUM (IL). CECUM (CE). COLON (CO). RECTUM (RE) SKIN (SK), MAMMARY, MALE (MR), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV). EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LM, TRACHBOBROM (TS), IN, ANT MR$/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE NARROW, STERNUM (SE), BONE, STERNUM AT MICROSCOPIC EXAMINATION: (SB), EYE (EY), BRAIN (BR), KIDNEY (XD), HEART (HT), GALLBLADDER (GS), SPLEEN (SP). THY14US (TH), ESOPHAGUS (ES), THYROID (TY). PARKTHYROID (PT). ADRENAL. MEDULLA (MA), AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SH). SPINAL CORD (SC). NERVE, SCIATIC (SN). STOMACH, GL (ST). DUODENUM (DtJ) JEJUNUM (JE), ILEUM (IL). CECUM (CE), RECTUM (RE), SKIN (SX), KRNKARY, MALE (MM). URINARY BLADDER (UB), PROSTATE (PR). SEMINAL VESICLES (SV), EPIDIDYKIDES (EP), TESTIS (TE) ----------- ----------------------------------------------------------------------------------------------- 701 APPENDIX 5 Individual Anatomic Pathology Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULFOUIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNONOTOGUS MOUMS ------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105519 SEXT MALE DOSE GROUPT 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 3140.0 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 RECORDER: TODD ACKER DATE AND TIME OF NECROPSY: 02/25/99 6:57 PROSECTOR: STEVE VAN ADESTINE WEIGHER: TODD ACKER P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T --A-VA-I-L-AB-L-E------------------P-A-TH-O-L-O-G--I--ST-3----R-OB-E-R-T --L-E-ED-L-E---------------------------------------------- ORGAN NAME ---------------------- LEFT ADRENAL (ADO) RIGHT ADRENAL (ADl) BRAIN (BR) LP EPIDIDYNIS (EPO) RT EPIDIDYNIS (EPl) LP KIDNEY (KDO) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TEO) RT TESTIS (TEl) PANCREAS (PA) LF THYROID/PARA RT THYROID/PARA (TTO) (TT1) GALLBLADDER (GB) ABSOLUTE ORGAN WRIGHT (GRAMS) -------- .2820 .2330 62.8980 .7730 .8270 5.5490 5.3860 53.1740 2.7780 2.9990 5.5570 .1310 .1220 .7260 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (t) -------- .0090 t .0074 t 2.0031 t .0246 t .0263 t .1767 t .1715 t 1.6934 t .0885 % .0955 t .1770 % .0042 % .0039 % ORGAN TO BRAIN WEIGHT RATIO -------- 0045 :0037 1.0000 .0123 .0131 .0882 .0856 .8454 .0442 .0477 .0683 .0021 .0019 0 R0A STA TU --------- WEIGHT WRIGHT WEIGHT WEIGHT WEIGHT WRIGHT WEIGHT WEIGHT WEIGHT WEIGHT WRIGHT WEIGHT WEIGHT WEIGHT -------B-I-L-E(-V-O-L-U-M-E-)----(B-I-)-----------------1-.-20-0-0--M-L----------------------------------------------------------------------- 0 BSE RVAT 10N S NECROPSY HISTOPATHOIOGY -------------------------------------------------- ---------------------------------------------------------------- BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-NODEMTELY SEVERE NARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) i -INFILTRATE, 14ACROPRAGES, PIGMENTED, PERIVASCULAI KIDNEY (KD) -INFILTRATE, LYMPHOHISTIOCYTIC,-NININAL 702 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105519 SEX: MALE DOSE GROUPs 1 SACRIFICE STATUS: STUDY DAY OF DEATH: 194 STUDY WEEK OF DEATHT 27 SCHEDULED, TERMINAL SACRI TERMINAL BODY WEIGHT: 31 REMRDER: TODD ACKER DATE OF DEATH: 02/25/99 DATE AND TIME OP NECROPSY: 02/25/99 6:57 PROSECTORT STEVE VAN ADESTIME WEIGHER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE ----------------------------------------------------------------------------------------------------------------- 0 B S E R V A T 1 0 N S (CONTINUED) HISTOPATHOLOGY NECROPSY ---------------------------------------------- ---------------------------------------------------------------- LUNG (LU) i _HYPERPLASIA, LYMPHOCYTIC, PERIBROt4CHIOLAR/P SLIGHT LIVER (LI) -INFILTRATE, LYMPHOHISTIOCYTIC,-KININAL, MM GALLBLADDER (GB) i -INFILTRATE, LYMPHOHISTIOCYTIC.-MININAL TRACHEA (TR) i -INFILTRATE. LYMPHOHISTIOCYTIC,-SLIGHT PARATHYROID (PT) -CYST,-PRESENT ADRENAL, CORTEX (AC) -INFILTRATE, LY14PHOHISTIOCYTIC,-MINZMAL SALIV GL, MANDIB (SG) t -INFILTRATE, LYMPHOHISTIOCYTIC,-NININAL JEJUNUM (JE) t * -INFILTRATE, MACROPHAGE, PIGMENTED.-HODERATI ILEM (IL) t -INFILTRATE, MACROPHAGE, PIGKENTED.-HODERATI CB= (CE) t -INFILTRATE, KACROPHKGB, PIGMENTED.-HODERAT, MAMMARY, MALE (HK) >SECTION EXKKINED; TISSUE NOT PRESENT PROSTATE (PR) : -INFLAMMATION, LYMPHOHISTIOCYTIC,-NINIMAL SPIDIDYNIVES (EP) : -HYPOSPERNIA,-MODERATE TESTIS (TE) i -IMMATURE.-PRESENT 703 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS -------------------------------------------------------------------------------------------------------------- SEX: MALE DOSE GROUP: I SACRIFICE STATUS: SCHEDU LED, TERMINAL SACRI ANIMAL NUMBER: 105519 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 31 RECORDER: TODD ACKER PROSECTORT STEVE VAN ADESTINE DATE AND TIME OF NECROPSY- 02/25/99 6:57 PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T--A-VA-I-L-A-BX-.-E----------------------------------------------------------------------------------- 0 B S R R V A T 1 0 N S (CONTINUED) HISTOPATHOLOGY NIECR6PSY ------ --------------------------------------- ----------------------------------------------------------------- GENERAL COMMEM (GC) : -BONE NARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - -- -- - - - - - - -- - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNRMRKABLE AT NECROPSY.- BONE. FEMUR (FE), MA"OW, FEKUR (FM), NARROW, STERNU.M (SE), BONE, STERNUM (SB), EYE (EY). BRAIN (BR) Ki SPLEEN (SP). THYMUS (TH) LN, NESENTERIC (MS), @RACE LUNG (LU), HEART (HT) . LIVER (LI), GALLBLADDER (GB) ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL: MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG). MUSCLE, SKELETAL (SH), SPINAL CORD (SC). NERVE, SCIATIC (SN). STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JR). ILEUM (IL), CECUM (CE), COLON (CO), RECTUM SKIN (SX), MAMMARY, 14ALE (MM), URINARY BLADDER (UB), PROSTATE (PR). SEMINAL VESICLES (SV), EPIDIDYKIDES TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB). IN, ANT MES/PANC (AP) THE FMOALRLROOWWI,NG STTEIRSNSUUMES (SWEE)E.TE BUONNREE,MASRKTAEBRLNEUM A(TSBM)I,CREOYSCEOPI(CEY), EXHAEMAIRNTATIO(NH:T), SPLEEN (SP), THY14US (TH), LM, KESENTERIC ESOPHAGUS (ES), THYROID (TY), ADRENAL, MEDULLA (MA). AORTA (AO), PITUITARY (PI). MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NEttVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), COLON (CO), RECTU SKIN (SK), URINARY BL.ADDER (UB), SEMINAL VESICLES (SV) ------------------------------------------------------------------------------------------------------------ 704 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULVONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105527 SEX: MALE STUDY DAY OF DEATH: DOSE 184 GROUP: I STUDY WEEK SACRIFICE OF DEATH: STATUST 27 SCHEDULED, TERMINAL SACRI TERMINAL BODY WEIGHTT 46 RECORDER: MICHELE ZI DATE OF DEATH: 02/25/99 PROSECTOR: KEVIN BILLINGS DATE AND TIME OF NECROPSY: 02/25/99 11:00 PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZlKi P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T--A-VA-I-L-A-BL-E---------------------------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0 ST ORGAN NAME (GRAMS) TO BODY WEIGHT (t) WEIGHT RATIO -------- --- ---------------------- -------- -------.0067 t .0048 WEI LEFT ADRENAL (ADO) RIGHT ADRENAL (ADl) .3120 .2600 .0056 % 1.3849 % .0040 WEI 1.0000 WEI BRAIN (ER) LF EPIDIDYMIS (EPO) 64.8130 1.IB660 .0399 t .0288 WEI .0274 WEI RT EPIDIDYMIS (EPI) 1.7750 7.5090 .0319 % .1604 t .1579 % .1159 WEI .1140 WEI LF KIDNEY RT KIDNEY (KDO) (KDI) 7.3890 1.3429 % .9697 WEI LIVER (LI) LP TESTIS (TEO) 62.8470 11.5730 .2473 t .2285 % .1786 WEI .1650 WEI RT TESTIS (TEl) 10.6940 6.0920 .1302 % .0940 WEI PANCREAS (PA) .2380 .0051 t .0037 WEI LF THYROID/PARA RT THYROID/PARA (TTO) (TT1) .2750 .0059 % .0042 WEI WEI GALLBLADDER (GB) .6430 -------B-I-L-E-(-VO-L-U-M-E-)----(B-I-)-----------------2-.4-0-0-0--m-L---------------------------------------------------------------- 0 BS ERVA T 10N S HISTOPATHOLOGY NECROPSY ------------------------------------------- ---------------------------------------------------------------- BONE, FEMUR (FE) : -GROWTH PLATE OPEN.-SLIGHT NARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE-NOT PRESENT BRAIN (BR) : -INFILTRATE, MACROPHAGES, PIGMENTED, PERI LUNG (LU) : -HYPERPLASIA, LYMPHOCYTIC, PERIBROWHIOLAR SLIGHT 705 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKZYS ------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: 105527 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI TERMINAL BODY WEIGHTT 46 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 RECORDER.- MICHELE ZIN DATE AND TIME OF NECROPSY: 02/25/99 11.00 PROSECTORT KEVIN BILLINGS PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZINA P-O-S-T--F-I-X-- W-E-I-GH-E-R-:---NO-T--4-V-A-I-LA-B-L-E----------------------------------------------------------------------------------- 0 B S B R V A T 1 0 N S (CONTINUED) HISTOPATHOLOGY NECR6PSY -------------------------------------------- ---------------------------------------------------------------- LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL. KUL -GRANULOMA,-MINIMAL, FOCAL THYMUS (TH) : -ATROPHY,-SEVERE SALIV GL, MANDIB (SG) -INFILTRATE, LYMPHOHISTIOCYTIC,-NINIKAL MUSCLE, SKELETAL (SM) z -INFILTRATE, LY14PHOHISTIOCYTIC.-MINIMAL DUODENUM (DU) : -INFILTRATE, MACROPHAGE, PIGKWED.-SLIGHT ILEUM (IL) i -INFILTRATE. MACROPRAGE, PIGMENTED,-MODERATE SKIN (SK) -ABRASION (S) /ULCERATION (S); 2.0 CH FROM TIP OF TAIL: SINGLE RED, MOIST ABRADED AREA, 0.8 CM IN DIAMETERs COLLECTED SKIN (SK) : -HYPERPLASIA. EPIDERMAL (ACANTHOSIS).-140DERM -INFLAMMATION, CHRONIC-ACTIVE,-SLIGHT -ULCERATION.-MODERATELY SEVERE URINARY BLADDER (UB) : -INFILTRATE,.LYMPHOHISTIOCYTIC,-NINIKAL GENERAL COMMENT (GC) -BONE NARROW SMEAR TAKEN - -E-YES- - -DAV-IDSO-NS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 706 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------- ANI14AL NUMBERT 105527 DATE OF DEATH: 02/25/99 SEX: 14ALE STUDY DAY OF DEATH: DOSE GROUP: I SACRIFICE 184 STUDY WEEK OF DEATH: PROSECTOR: KEVIN BILLINGS STATUS: 27 SCHEDULED, TERMINAL SACR TERMINAL BODY WEIGHT: 4 RECORDER: MICHELE ZI DATE AND TIME OF NECROPSY: 02/25/99 11:00 POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIN --------------------------------------------------------------------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), NARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KI LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), IN, MRSENTERIC (MS), TRAC ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT). ADRENAL, CORTEX (@LC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYNIDES (EP), TESTI ADIPOSE TISSUE (AT), LN, TRACHBOBRON (TB), IN, ANT 14ES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), KIDNEY (KD), HEART (HT). GALLBLADDER (GB), SPLEEN (S IN. NESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL. CORTEX (AC) ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SPINAL CORD (SC). Ng]kVE, SCIATIC (SN), STOMACH, GL PANCREAS (PA)@ JEJUNUM (JE), CECUM (CE), COLON (CO), RECTUM (RE). MAMMARY, MALE (MH), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE) ---------------------------------------------------------------------------------------------------------------- 707 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT IPFOS;T-6295) IN CYNOMOLCUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105514 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 34 DATE AND TIME OF NECROPSY: 02/25/99 9:21 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIKA ----------------------------------------------------------------------------------------------------------------- ORGAN NAME ---------------------- ABSOLUTE ORGAN WEIGHT IGRAHS) -------- ORGAN WEIGHT RELATIVE TO BODY WEIGHT (t) -------- ORGAN TO BRHIN WEIGHT RATIO -------- 0R ST ---- LEFT ADRENAL (ADO) RIGHT ADRENAL (ADl) .3620 .2420 .0104 % .0069 % .0058 .0039 WEIG WEIG BRAIN IBR) - 62.4280 1.7862 % 1.0000 WEIG LF EPIDIDYMIS (EPO) 1.1580 .0331 % .0185 WEIG RT EPIDIDYMIS (EPI) 1.0010 .0286 % .0166 WEIG LF KIDNEY (KDO) 6.0230 .1723 % .0965 WEIG RT KIDNEY (KD1) 6.1700 .1765 % .0988 WEIG LIVER ILI) 64.2170 1.8374 % 1.0287 WEIG LF TESTIS ITEO) 6.7090 .1920 t .1075 WEIG RT TESTIS (TEl) 5.1600 .1476 t .0827 WEIG PANCREAS (PA) 4.7970 .1373 % .0768 WEIG LP THYROID/PARA (TTO) .3130 .0090 t .0050 WEIG RT THYROID/PARA (TT1) .3200 .0092 t .0051 WEIC ----------------------------------------------------------------------------------------------------------------- 0B SERV AT10N 8 NECROPSY HISTOPATHOLOGY ------------------------------------------------------------------------------------------------------------ LUNG (LU) : -ADHESIONIS); ALL LOBES TO EACH OTHER, PLEURA, PERICARDIAL SAC, AND CAUDAL LOBES TO DIAPHRAGM: MULTIPLE RED, TAN. FIBROUS ADHESIONS; COLLECTED INTACT CENERAL COMMENT (CC) -BONE HARROW SMEAR TAY" LUNG (LU) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL LIVER (LI) -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIKhL, MU THYMUS (TH) : -ATROPHY,-MOD M TE -EYES - DAVIDSONS APPENDIX S individual Anatomic Pathology Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PM LUOROOCTANE SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105514 SEX; MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 34 DATE AND TIME OF NECROPSY.- 02/25/99 9:21 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZI POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ----------------------------------------------------------------------------------------------------------------- 0 B S E R V A T 1 0 N S (CONTINUED) NECROPSY HISTOPATHOLOGY ------------------------------------------------------------------------------------------------------------ GENERAL INFORMATION (XX) : >NOTE: >GALLBLADDER WEIGHT IS 0.7220 GRAMS BILE VOLUME IS 1.4000 ML - - - - - - - - - ---- - - - - -- - - - - - -- - - - - - - -- - - -- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR, (FE) , MARROW, FEMUR (FM), HARROW, STERNUM (SE), SOME, STERNUM ISBI, EYE (EY), BRAIN (BR), KI HEART (HT). LIVER (LI), GALLBLADDER (GS), SPLEEN (SP). THYMUS (TH), LN, MRSENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), -RHYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA IAO). PITUITARY (PI), SALIV CL, MANDIS (SG), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST) , DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM ICE), COLON (CO), RECTUM SKIN (SK), MAHMAJRY. MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHBOBRON (TB), IN, ANT NES/PANC (AP) ----------------------------------------------------------------------------------------------------------------- APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLCUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 10551S SEX: HALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH.- 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WRIGHT: 34 DATE AND TIME OF NECROPSY: 02/26/99 6:45 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HAL POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER- JOHN S. HALF ----------------------------------------------------------------------------------------------------------------- ORGAN NAME ---------------------- ABSOLUTE ORGAN WEIGHT (CRHMS) -------- ORGAN WEIGHT RELATIVE To BODY WEIGHT -------- ORGAN TO BRAIN WEIGHT RATIO -------- 0R ST ---- LEFT ADRENAL (ADO) .2770 .0080 .0043 WEIG RIGHT ADRENAL BRAIN (BR) (ADl) .1900 63.7670 .0055 1.8350 .0030 1.0000 WEIG WEIG LF EPIDIDYMIS (EPO) .759o .0216 .0119 WEIG RT EPIDIDYMIS (Epi) LP KIDNEY (KDO) .8690 6.4220 .0250 .1848 .0136 i007 WEIG WEIG RT KIDNEY IKD1) 6.2010 .1784 t .0972 WEIG LIVER (LI) 55.8260 1.6065 t .875S WEIG LF TESTIS RT TESTIS PANCREAS (TEO) (TEI) (PA) 2.7190 3.3300 5.0260 .0782 t .0958 t .1446 t .0426 .0522 .078& WEIG WEIG WEIG LF THYROID/PARA (TTO) .1340 .0039 t .0021 WHIG RT THYROID/PARA (7rl) .1240 .0036 % .0019 WEIG ----------------------------------------------------------------------------------------------------------------- 0 B S 9 R V A T 10 N S NECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- GENERAL COMMENT (GC) -BONE NARROW SHEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS LIVER (LI) ; -INFILTRATE, LTMPHOHISTIOCYTIC,-MINIKAL, mu GENERAL INFORMATION (XX) >NOTE: >CALLIBLADDER WEIGHT IS 0.4620 GRAMS BILE VOLUME IS 1.2000 ML - - - - - - - - --- - - - -- - - -- - -- - - - - - - - -- - - - - - - APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) In CYNOMOLCUS MONKEYS ------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: 105515 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TMU41NAL SACRI DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 347 DATE AND TIME OF NECROPSY: 02/26/99 6:45 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HAL POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALF( ----------------------------------------------------------------------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR IFE), KHRROW, FEMUR (FMI, MARROW, STERNUM (SE), BONE. STERNUM ISB). EYE (EY), BRAIN (BR), KI LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THY14US (TH), IN, NESENTERIC (MS), TRACH ESOPHAGUS (ES) , THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA IMA). AORTA (AO), PITUITARY (PI) , SALIV GL, KANT)IB (SG), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JrE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER IUB), PROSTATE (PR), SEMINAL VESICLES ISV), EPIDIDYMIDES TESTIS (TE), AX)IPOSE TISSUE (AT), LN, TRACHROBRON (TS), t.N, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: THYMUS (TH) ----------------------------------------------------------------------------------------------------------------- APPENDIX 5 individual Anatomic Pathology Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: TOSS16 DATE OF DEATH: 02/26/99 DATE AND TIME OF NECROPSY: SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 02/26/99 7:15 PROSECTOR: KEVIN BILLINGS SCHEDULED, TERMINAL SACRI TERMINAL BODY WEIGHT: 31 RECORDER: MICHELE ZIK POST-FIX WEIGHER: NOT AVAILA.BLE PATHOLOGIST: ROBERT T-PP LE WEIGHER: MICHELE Z114A ----------------------------------------------------------------------------------------------------------------- ORGAN NAME ---------------------- ABSOLUTE ORGAN WEIGHT (GRAMS) -------- ORGAN WEIGHT RELATIVE TO BODY WEIGHT -------- ORGAN TO BRAIN WEIGHT RATIO -------- 0R ST ---- LEFT ADRENAL RIGHT ADRENAL BRAIN (BR) (ADO) (ADl) .2940 .2410 67.0240 .0093 .0076 2.1143 .0044 .0036 1.0000 WRIG WEIG WEIG LP EPIDIDYMIS (EPO) .8820 .0278 .0132 WEIG RT EPIDIDYNIS (EPl) .7570 .0239 .0113 WEIG LF KIDNEY (KDO) 6.9380 .2157 t .1020 WEIG RT KIDNEY (KDI) 7.0240 .2216 * .1048 WEIG LIVER (LI) 68.1040 2.1484 % 1.0161 WEIG LP TESTIS (TEO) 3.3570 .1059 % .0501 WEIG RT TESTIS (TEl) 5.1290 .1618 % .0765 WEIG PANCREAS (PA) 3.0500 .0962 % .0455 WRIG LF THYROID/PARA (TTO) .2040 .0064 % .0030 WEIG RT TliYROID/PARA (7Tl) .1430 .004S 4 .0021 WEIG ----------------------------------------------------------------------------------------------------------------- 0 B S B R.V A T 1 0 N S NECROPSY HISTOPATHOLOGY ------------------------------------------------------------------------------------------------------------ SPLEEN (SP) : SPLEEN (SP) : -LARGE: 7. 0 X S.0 X 3. 0 CM >NOT REQUIRED TO BE MMn= FOR ANIMAL THYMUS (TH) : TESTIS ITE) -CYST,-PRESENT TESTIS (TE) : -LARGE: RIGHT: 2.5 X 1.5 X 1.4 CM (FOR COMPARISON, LEFT IS ->NOT REQUIRED TO BE EXAMINED FOR ANIMAL 2.0 X 1.5 X 1.0 CM) GENERAL COKHMM (CC) -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS APPENDIX 5 Individual Anatomic Pathology Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULFONIC ACID POTASSIUM SALT (PFOS;T-629S) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105516 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 31 DATE AND TIME OF NECROPSY: 02/26/99 7:lS PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZI POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ----------------------------------------------------------------------------------------------------------------- 0 B S E R V A T 1 0 H S ICONTINUED) HECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- GENERAL INFORMATION (XX) : >NOTE: >GALLBLADDER WEIGHT IS 0.6300 GRAMS BILE VOLUME IS 1.4000 ML - - - - - - - - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE) , NARROW, FEMUR (FM) , MARROW, STERNUM (SE)o BONE, -STERNUM (SB) , EYE (EY) . BRAIN (BR) , KI LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GS), THYMUS (TH), LN, NESENTERIC (MS), TRACHEA (TR) ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA *(AO), PITUITARY (PI), SALIV CL, HANDIB (SGI, MUSCLE, SKELETAL (SM), SPINAL CORD ISC), NERVE, SCIATIC (SN), STOMACH, CL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM IJE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM SKIN (SX), MAMMARY, KALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMn4AL VESICLES (SV), EPIDIDYMIDES ADIPOSE TISSUE 4AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (") THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: LIVER (LI) ---------------------------------------------------------------------------------------------------------------- APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLCUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: IOS52:t SEX: MALE DOSE GROUP: 2 ' SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGNT: 43 DATE AND TIME OF NECFTOPSY: 02/26/99 10:48 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIK POST-FIX WEIGHER: NO'r AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIHA ----------------------------------------------------------------------------------------------------------------- ORGAN NAME ---------------------- ABSOLUTE ORGAN WEIGHT (GRAMS) -------- ORGAN WEIGHT RELATIVE TO BODY WEICHT -------- ORGAN TO BRAIN WEIGHT RATIO -------- 0R ST ---- LEFT ADRENAL (ADO) .3090 .0070 % .0057 WEIG RIGHT ADRENAL BRAIN (BR) IADl) .2230 53.9SOO .0051 t 1.2305 t .0041 WRIC 1.0000 WEIG LF EPIDIDYMIS (EPO) 2.8840 .0658 % .0534 WEIG RT EPIDIDYMIS (EPl) 2.7980 .0638 % .0519 WEIG LP KIDNEY (KI)O) 7.1230 .1624 t .1320 WEIG RT KIDNEY (KD1) 7.6030 .1734 % .1409 WEIG LIVER (LI) 60.2000 1.3729 % 1.1157 WEIG LP TESTIS RT TESTIS (TIMO) IT]EL) 18.7540 18.8730 .4277 % .4304 % .3476 WEIG .3498 WEIG PANCREAS (PA) 6.3800 .1455 % .1182 WEIG LF THYROID/PARA (7rO) .4490 .0102 % .0083 WEIG RT THYROID/PARA (7Tl) .4660 .0106 % .0086 WEIG ----------------------------------------------------------------------------------------------------------------- 0b SERVA T10N S NECROPSY HISTOPATHOLOOGY -------------------------------------------------------------------------------------------------------------- LIVER ILI) : -INFILTRATE, LYHPHOHISTIOCYTIC,-KINI14AL, mu -VACUOLATION, HEPATOCELLULAR,-MINIMAL, -STASIS, BILE,-MODERATE, MULTI-FOCAL MULTI THYMUS (TH) : -ATROPHY,-MODERATELY SEVERE GENERAL COMMENT (GC) -BONE MARROW SHEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LP-SIONS APPENDIX S Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLOUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105521 DATE OF DP-ATH: 02/26/99 DATE AND TIME OF NECROPSY: SEX: MALE DOSE GROUP: 2 SACRIFICE STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 02/26/99 10:48 PROSECTOR: KEVIN BILLINGS STATUS: 27 SCHEDULED, TERMINAL SACRI TERMINAL BODY WEIGHT: 43 RECORDER: MICHELE ZIM POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WE.IGHER: MICHELE ZIMA ----------------------------------------------------------------------------------------------------------------- 0 B S E R V A T 1 0 N S (CONTINUED) NECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- GENERAL INFORMATION (XX) : >NOTE: >GALLBLADDER WEIGHT IS 0.4810 GRAMS BILE VOLUME IS 1.4000 ML - - - - - - - - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGA.NS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (IFE), MARROW, FEMUR (FM), NARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KI LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS ITH), IN, MESENTERIC (MS), TRACH ESOPHAGUS (ES) , 7"YROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL. MEDULLA (KA), AORTA (AO), PITUITARY (PI) , SALIV GL, MANDIS (SC), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOKACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUH (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM SKIN (SK), MA24MARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV). EPIDXDYNIDES TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT NES/PANC (AP) ----------------------------------------------------------------------------------------------------------------- APPENDIX Individual Anatomic Pathology Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOWOLCUS MONKEYS ------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: 105510 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUSZ SCHEDULED, TERMINAL SACRIF DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 195 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 318 DATE AND TIME OF NECITOPSY: 02/26/99 9:48 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZITU POST-FIX WEIGHER: NO'r AVAILABLE PATHOLOGIST-. ROBERT LEEDLE WEIGHER: MICHELE ZIKA ------------------------------------------------------------------------------------------------------------------ ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0R ORGAN NAME ---------------------- (GRAMS) -------- TO BODY WEIGHT (%) -------- WEIGHT RATIO -------- ST ----- LEFT ADRENAL RIGHT ADRENAL BRAIN (ER) (ADO) (ADl) .2490 .1600 56.7600 .0078 % .0050 % 1.7849 % .0044 .0028 1.0000 WRIC weir. WEIG LF EPIDIDYMIS (EPO) RT EPIDIDYNIS (EP1 I LF KIDNEY (KDO) 1.0910 1.0?SO 6.4950 .0343 t .0338 t .2042 % .0192 .0189 .2144 WEIG WRIG WEIG RT KIDNEY lkml) LIVER (LI) LF TESTIS (rEO) RT TESTIS (TEl) 6.1190 54.2060 6.0950 5.8860 .1924 % 1.7046 t .1917 % .19si % .1078 .9550 .1074 .1037 WEIG WEIG WEIG WEIG PANCREAS (PA) 3.8800 .1220 t .0684 WEIG LF THYROID/PAJtA ITTO) .1660 .0052 t .0029 WEIG RT TliYROID/PARA (TT1) .1960 .0062 % .0035 WRIC ----------------------------------------------------------------------------------------------------------------- 0 B SE R V A T 1 0 N S NECROPSY HI M PATHOLOGY -------------------------------------------------------------------------------------------------------------- LUNG (LU) : -ADHESION(S); BIE.ATEM CAUDAL LOSES TO PLEURA AND DIAPHRAGM: MULTIPLE TAN, FIBROUS ADHESIONS; COLLECTED INTACT ADIPOSE TISSUE (AT) : -RAISED FOCUS (1) /AREA (S.); DIFFUSE, THROUGHOUT NESMURRY AND THORACIC CAVITY: MULTIPLE, TAN, FIRM NODULES, UP TO 0.6 CH LUNG (LU) >NOT REQUIRED ADIPOSE TISSUE >NOT REQUIRED TO BE EXAMINED (AT) TO BE EXAMINED FOR ANIMAL FOR ANIMAL IN DIAMETER WITHMN MESENTERY (CAP 29), UP To 0. 3 CM IN DIAMETER WITHIN 'RHORACIC CAVITY (CAP 30) AND COLLECTED INTACT WITH LUNG ADHESIONS GENERAL COMMENT (GC) : -BONE KARP.OW SMEAR TAKEN -EYES - DAVIDSONS APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT IFFOS;T-6295) IN CYNONOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: 1055:10 DATE OF DEATH: 02/26/99 DATE AND TIME OF NECROPSY: SEX: MALE STUDY DAY OF 02/26/99 9:48 DOSE GROUP: 3 SACRIFICE DEATH: 185 STUDY WEEK OF DEATH: PROSECTOR: KEVIN BILLINGS STATUS: 27 SCHEDULED, TERMINAL SACRIF TERMINAL BODY WEIGHT: 318 RECORDER: MICHELE ZIM) POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ------------------------------------------------------------------------------------------------------------------ 0 B S E R V A T 1 0 N S (CONTINUED) NECROPSY HISWPATHOLOGY -------------------------------------------------------------------------------------------------------------- GENERAL INFOR14ATION >NOTE: >GALLBLADDER (XX) : WEIGHT IS 0.6690 GRAMS'BILE VOLUME IS 2.400o ML - - - - - -- --- - -- - - -- - - -- - - - - - - - -- - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), KARROW, FEMUR (PH), HARROW, STERNUM (SE), BONE, STERNUM (SB). EYE (EY), BRAIN (BR), KID] HEART (HT). LIVER (LI), GALLBLADDER (GE), SPLEEN (SP), THY14US (TH), LN, NESENTERIC INS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (KA). AORTA (AO), PITUITARY (PI), SALIV CL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN). STOMACH, GL. (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JR), ILEUM IIL), CECUM (CE), COLON (CO), RECTUM SKIN (SK), MAMMARY, MALE (MM), URINARY-BLADDER (UB), PROSTATE (PR). SEMIM VESICLES lsv), EPIDIDYMIDES TESTIS (TE) , LN, TRACHEOBRON (TB), IN, ANT NES/PANC (AP) THE FOLLOWING *RISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION.* LIVER (LI), THYMUS (TH) ----------------------------------------------------------------------------------------------------------------- APPENDIX S individual Anatomic Pathology Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------7 ---------------------------------------------------------------------------- ANIMAL NUMBER: 105518 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH. 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 30 DATE AND TIME OF NECROPSY: 02/26/99 9.-20 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZI POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE Z114A ----------------------------------------------------------------------------------------------------------------- ABSOLUTE ORCM WRICHT ORCAN NAME ---------------------- (GRAMS) -------- ORGAN WEIGHT RELATIVE TO BODY WEIGHT (t) -------- ORGAN TO BRAIN WEIGHT RATIO -------- LEFT ADRENAL IADO) RIGHT ADRENAL (ADl) .2790 .2460 .0091 t .0080 t .0044 .0039 BRAIN (BR) LP EPIDIDYMIS (EPO) 62.8420 .8790 2.0470 % .0286 % 1.0000 .0140 RT EPIDIDYMIS IEPl) LF KIDNEY (KDO) RT KIDNEY (KD1) LIVER (LI) 1.0970 5.6790 5.6110 S7.S930 .0357 % .1850 % .1828 % 1.8760 % .0175 .0904 .0893 .9165 LF TESTIS (TEO) RT TESTIS (TRI) PANCREAS (PA) LF THYROID/PARA (TTO) 4.5720 4.6220 3.1580 .2450 .1489 t .1506 % .1029 % .0080 % .0728 .0735 .0503 .0039 RT TliYROID/PARA (TTI) .3110 .0101 % .0049 ----------------------------------------------------------------------------------------------------------------- 0R 5T ---- WEIG WEIG WEIG WEIG WEIG WEIG WEIG WRIG WEIG WHIG WEIG WEIG WEIG 0BS RRVAT 10N S NECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- THYMUS (TH) : -ATROPHY,-MINIMAL GENERAL COMNNM (GC) -BONE NARROW SHEAR TAKEN -EYES - DAVIDSONS -NO MHCROSCOPIC LESIONS GENERAL INFORMATION (XX) >NOTE: >GALLBLADDER WEIGHT IS O.S320 GRAMS BILE VOLUME IS 1.3000 ML - - - - - - - - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - APPENDIX 5 Indiviclual Anatomic Pathology Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PMWLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLCUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105518 SEX: KALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACF DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 18S STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3 DATE AND TIME OF NECROPSY. 02/26/99 9:20 PROSECTOR: MIN BILLINGS RECORDER: MICHELE ZI POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT f LE WEIGHER: MICHELE ZI ---------------------------------------------------------------------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT WECROPSY: DONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (BY), BRAIN (BR), K LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB)f SPLMM (SP), THYMUS (TH), LN, NESENTERIC (MS), TRA( ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO) PITUITARY (PI), SALIV GL, KANDIB (SO), MUSCLE, SKELETAL (SH). SPINAL CORD (SC). IUMVE, SCIATIC (SN), STOMACH, CL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (Col. RECTU SKIN (SK), HANKHRY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES TESTIS (TE) , ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB) .@LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: --------L-I-V-E-R--(-L-I-)---------------------------------------------------------------------------------------------- APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOHIC ACID POTASSIUM SALT (PFOS:T-629S) IN CYNOMOL(;UG MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: IOSS24 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WRIGHT: 30 DATE AND TIME OF NECROPSY, 02/26/99 7:42 PROSECTOR: STI= VAN ADESTINE RECORDER: JOHN S. HAL POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALF ----------------------------------------------------------------------------------------------------------------- ORGAN NAME ---------------------- ABSOLUTE ORGAN WEIGHT (GRAMS) -------- ORGAN WEIGHT RELATIVE TO BODY WEIGHT (1k) -------- ORGAN TO BRAIN WRIGHT RATIO -------- 0R ST ---- LEFT ADRENAL (ADO) .2420 .0080 % .0038 WEIG RIGHT ADRENAL (ADl) .1860 .0061 % .0029 WEIG BRAIN IER) 63.9330 2.106S % 1.0000 WEIG LF EPIDIDYNIS (EPO)- .9350 .0308 % .0146 WEIG RT EPIDIDYHIS (EPl) .9840 .0324 % .0154 WEIG LF KIDNEY (RDO) 5.0370 .1660 % .0788 WEIG RT KIDNEY (KDI) 4.8440 .1596 t .07SB WEIG LIVER (LI) 52.5550 1.7316 t .8220 WEIG LF TESTIS ITEO) 4.6940 lS47 % .0734 WEIG RT TESTIS (TEl) 4.2750 .1409 % .0669 WEIG PANCREAS (PA) 4.6550 .1534 % .0728 WEIG LF THYROID/PARh (TrO) .1210 .0040 % .0019 WEIG RT THYROID/PARA (TT1) .1330 .0044 % .0021 WEIG ----------------------------------------------------------------------------------------------------------------- 0bSB RVAT 10N 5 NECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- THYMUS (TH) : GENERAL COMMENT (GC) -ATROPHY,-MINIHAL -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS GENERAL INFORMATION (XX) >NOTE: >GALLELADDElt WEIGHT IS 0.9610 GRAMS BILE VOLUME IS 0.8000 ML - - - - - - - --- - - - -- - -- - - - - - -- - - - -- - - -- - -- - APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PP"LUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLOUS MON M 9 ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105524 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 30 DATE AND TIME OF NEC!ROPSY: 02/26/99 7:42 PROSECTOR: STEVE VAN ADESTIM RECORDER: JOHN S. HA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST- ROBERT LEEDLE WEIGHER: JOHN S. HALF ----------------------------------------------------------------------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), 13ONE STERNUM (SB), EYE (BY), BRAIN (BR), KI LUNG (LU), HF.ART (HT), LIVER (LI), GALLBLADDER (GB), SPI-Ring(SP): THYMUS (TH), LN, NESMNMUC (MS), TRACH ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX IAC), ADRENAL, UMMLLA (KA), AORTA (AOI, PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SH), SPINAL CORD (SC). NERVE, SCIATIC (SN). STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE). ILEUM (IL), CECUM (CE), COLON (CO). RECTUM SKIN (SK), MAMMARY, MALE (KH), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYKIDES TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHROBRON (TB), LN, ANT MES/PANC THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: LIVER (LI) ----------------------------------------------------------------------------------------------------------------- APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULPONIC ACID POTASSIUM SALT (PFOST-629S) IN CYNOMOLCUS MONKEYS ------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: 105529 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WRIGHT: 34 DATE AND TIME OF NEC3tOPSY. 02/26/99 10:19 PROSECTOR: KEVIN BILLINGS RECORDER- MICHELE ZIMJ POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ----------------------------------------------------------------------------------------------------------------- ORGAN NAME ---------------------- ABSOLUTE ORGAN WRIGHT (GRAMS) -------- ORGAN WRIGHT RELATIVE TO BODY WEIGHT (t) -------- ORGAN To BRAIN WEIGHT RATIO -------- 0R ST ---- LEFT ADRENAL (ADO) RIGHT ADRENAL (ADl) BRAIN (BR) LP EPIDIDYMIS (EPO) RT EPIDIDYMIS (EPl) LP KIDNEY (KDO) .3070 .2620 69.8730 .9990 .9290 6.3390 .0088 t .0075 t 2.0107 % .0287 t .0267 t .1824 % .0044 .0037 1.0000 .0143 .0133 .0907 WEIG WEIG WRIC WEIG WEIG WEIG RT KIDNEY (Ml) LIVER (LI) LF TESTIS (TEO) 6.3690 64.9760 5.0300 .1833 t 1.8698 t .1447 t .0912 .9299 .0720 WEIG WEIG WEIG RT TESTIS (TEl) 5.2350 .1566 t .0749 WEIG PANCREAS (PA) 5.8230 .1676 % .0833 WEIG LF THYROIDIPARA (7TO) .2980 .0086 4 .0043 WEIG RT THYROID/PARA (TT1) .3900 .0112 % .0056 WEIG ----------------------------------------------------------------------------------------------------------------- 0B SBRVAT X0N S NECROPSY HISTOPATHOtdOGY ---------------------------------------------------------------- ---------------------------------------------- LIVER (LI) : -INFILTRATR, LYMPHOHISTIOCYTIC,-MINIMAL, -HYPERTROPHY, HEPATOCELLULAR,-SLIGHT, THYMUS (TH) : HU DIFFUS GENERAL COMMENT (GC) -ATROPHY,-SLIGHT -DONE MARROW SMEAR TAKEN -EYES - D)LVIDSONS -NO MACROSCOPIC LESIONS GENERAL INFORMATION (XX) >NOTE: >GALLBLADDER WEIGHT 19 0.5220 GRAMS BILE VOLUME 19 1.8000 ML APPENDIX s Individual Anatomic Pathology Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PMTFLUOPOOCTANE SULPONIC ACID POTASSIVN SALT (PPOS;T-6295) IN CYNONOLOUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105528 DATE OF DEATH: 02/26/99 DATE AND TIME OF NECROPSY: SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: STUDY DAY OF DEATH: 18S STUDY WEEK OF DEATH: 27 02/26/99 10:19 PROSECTOR: KEVIN BILLINGS SCHEDULED, TERMINAL SACRI TERMINAL BODY WEIGHT: 34 RECORDER: MICHELE ZIK POST-FIX WEIGHER: NOT AVAILABLE PATHOLO(;IST* ROBERT LEEDLE WEIGHER: MICHELE ZIMA ----------------------------------------------------------------------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE. FEMUR (FE), MARROW, FEMUR (FM), NARROW, STERNUM (SE), DONE, STERNU14 (SB), EYE (BY), BRAIN IBR), KI LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LM, NESENTERIC (MS). TRACH ESOPHAGUS (ES), THYROID ITY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV OL, MANDIB (SG), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM SKIN (SK), HAMKARY, MALE (MM), URINARY BLADDER (US), PROSTATE (PR), SEMINAL VESICLES (OV), EPIDIDYMIDES TESTIS (TE) , ADIPOSE TISSUE (AT), LN, TRACHEORRON (TB), E.N, ANT MES/PANC (AP) ----------------------------------------------------------------------------------------------------------------- APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER- 105507 SEX: MALE DOSE GROUP: A SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/25/99 DATE AND TIME OF NECROPSY: STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 02/25/99 8:11 PROSECTOR: STEVE VAN ADESTINE TERMINAL BODY WEIGHT: 38 RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ----------------------------------------------------------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0R ORGAN NAME ---------------------- (GRAMS) -------- TO BODY WEIGHT (t) -------- WEIGHT RATIO -------- ST ---- LEFT ADRENAL (ADO) RIGHT ADRENAL (ADl) BRAIN (BR) LP EPIDIDYHIS (EPO) RT EPIDIDYNIS (EPl) LF KIDNEY (KDO) RT KIDNEY (KDI) LIVER (LI) LF TESTIS (TEO) RT TESTIS (TEI) PANCREAS (PA) LF TNYROID/PAR& (TTO) RT'THYROID/PARh (TT1) GALLBLADDER (GB) .4540 .3210 71.7900 2.0740 2.3260 6.5150 6.2950 112.4190 12.6370 12.5000 5.2280 50 .28 .3460 .5330 .0117 t .0083 t 1.8550 t .0536 t .0601 t .1683 t .1627 % 2.9049 t .3265 t .3230 t 1351 t :0074 % .0089 t .0063 .0045 1.0000 .0209 .0324 .0908 .0877 1.5659 .1760 .1741 .0726 .0040 .0048 WEIG WEI WEIG WEIG WEIG WEIG WEI WEIG WEIG WEIG WEIG WEI WEIG WHIG BILE(VOLUME) (BI) 2.0000 ML ----------------------------------------------------------------------------------------------------------------- 1 0B SERV AT 10N S NECROPSY HISTOPATHOLOGY ------------------------------------------------------------------------------------------------------------- BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-SLIGHT MARROW. FEMUR (FN) : >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) t -INFILTRATE, -INFILTRATE, LYMPHOHISTIOCYTIC, PERIVASCULAR MACROPHAGES, PIGMENTED, PERIVAS KIDNEY (KD) : -INFILTRATE, LYMPHOHISTIOCYTIC.-MINIMAL -MINERALIZATION, CORTEX,-MINIMAL 724 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK-CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PFOS:T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------- SACRIFICE STATUS: SCHEDULED. TERMINAL SACRIF ANIMAL NUMBER: 105507 SEX. 14ALE DOSE GROUP: 4 . STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 367 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: led PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER DATE AND TIME OF NECROPSY: 02/25/99 8:11 PATHOtOGISTt ROBERT LUEDLE WHIGHERT TODD ACKER P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T --A-V-AI-L-A-B-LE----------------------------------------------------------------------------------- 0 B S E R V A T 1 0 N S (CONTINUED) HISTOPATHOLOGY NECROPSY --------------------------------------------------------------- ------ --------------------------------------LIVER (LI) : LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR.-HODERATE, DIFR -MOTTLED; ALL LOBES: BROWN AND TAN -VACUOLATION, HEPATOCELLULKR, CENTRIT.OBULAR, SEVERE THYMUS (TH) -CYST,-PRESENT -ATROPHY,-MODERATELY SEVERE IN, NESENTERIC (MS) LN, NESENTERIC (MS) -DIFFUSELY RED; DARK RED ADRENAL, CORTEX (AC) -DIFFUSELY DARK; 131LATERAL: DARK BROWN >UNREMRKABLE TRACHEA (TR) t -INFILT,RATE. LYMPHOHISTIOCYTIC.-SLIGHT ADRENAL CORTEX (AC) >UNREMARKABLE JEJUNUM (JE) : -INFILTRATE, MACROPHAGE, PIGIUMED,-MODERATI ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGMENTED,-NODERAT PROSTATE (PR) : -INFLAMMATION, LYMPHOHISTIOCYTIC,-MINIMAL GENERAL COMMENT (GC) -BONE 14ARROW SHEAR TAKEN -EYES - DAVIDSONS - - - - - - - - -- - - - - - - - -- - - - - - - - - - - - - - - - -- 725 APPENDIX 5 Individual Anatomic PathologY Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAiqE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ----------- ------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105507 SEX: MALE DOSE GROUP. 4 SACRIFICE STATUS: STUDY WEEK OF DEATH: 27 SCHEDULED, TERMINAL SACRI TERMINAL BODY WRIGHT: 30 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 DATE AND TIME OF NECITOPSY: 02/25/99 8:11 PROSECTORT STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TOM ACKER ----------------------------------------------------------------------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), NARROW. FEMUR (FH), NARROW, STERNUM (SE), BM, STERNUM (SB), EYE (BY), BRAIN (BR), KI LUNG (LU), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), TRACHEA (TR), ESOPHAGUS (ES). THYROID PARATHYROID (PT), ADRENAL. MEDULLA (MA), AORTA (AO), PITUITARY (PI). SALIV GL, MKNDIB (SG), MUSCLE, SKE SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA). JEJUMM (JE), ILEO CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, 14ALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV). EPIDIDYKIDES (EP). TESTIS (TE), ADIPOSE TISSUE (AT), IN, TRACHEOBROM (TB), LN, ANT NES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE MARROW, STEP.NM (SE). BONE, STERNUM AT MICROSCOPIC EXAMINATION: (SB), EYE (EY), LUNG (LU), HEART (HT), GALLBLADDER (GS). SPLEEN (SP). ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (KA), AORTA (AO), PITUITARY (PI), SALIV GL. MA34DIB (SG). MUSCLE, SKELETAL (SH). SPINAL CORD (SC). NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU). PANCREAS (PA). CECUM (CE), COLON (CO). RECTUM (RE), SKIN (SK), MAMMARY, KALE (MM), URINARY BLADDER (UB), SEMINAL VESICLES (SV), EPIDIDY14XDES (HP), TESTIS (TE) ---------------------------------------------------------------------------------------------------------------- 726 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105512 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRII TERMINAL BODY WEIGHT: 22 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 RECORDER: TODD ACKER DATE AND TIME OF NECROPSY- 02/25/99 9:21 PROSECTORT STEVE VAN ADESTINE WEIGHER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE -------------------------------------------------------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0R ORGAN NAME (GRAMS) TO BODY WEIGHT (t) WEIGHT RATIO -------- ST --- - ------------ ------- -------- -------- LEFT ADRENAL (ADO) (ADl) .2790 .2240 .0122 t .0098 t .0046 .0037 1.0000 WEIG WEIG WEIG RIGHT ADRENAL BRAIN (BR) 60.7370 2.6581 % .0239 % .0090 WEIG LF EPIDIDYMIS (EPO) .5450 .4350 .0190 t .0072 WEIG RT EPIDIDYNIS (Epl) 4.5470 .1990 t ..0749 WEI LF KIDNEY RT KIDNEY (KDO) (KDI) 4.5140 .1975 t .0743 .,9573 WHIG WHIG LIVER (LI) LF TESTIS (TEO) 58.1440 1.4310 1.3310 2.5446 t .0626 t .0582 t .0236 .0219 WHIG WEIG RT TESTIS (TEI) 3.0430 .1332 % .0501 WHIG PANCREAS (PA) LF THYROID/PARA (TTO) .1190 .0052 t .0020 .0021 WEIG WEIG RT THYROID/PARA (TTi) .1260 .0055 t WEIG GALLBLADDER (GB) .3100 -------B-IL-E-(-V-OL-U-M-E-)-----(-B-I-)-----------------1-.2-0-0-0--m-L--------------------------------------------------------------- 0 BS ERVA T 10N 9 HISTOPATHOT.OGY NECROPSY -------------------------------------------- ---------------------------------------------------------------- BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-MODERATE MARROW, FEMUR (FM) i >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) : -INFILTRATE, MACROPRAGES, PIGMENTR . PERIVXI LIVER (LI) t -MOTTLED; ALL LODES: BROWN AND TAN LIVER (LI) g -HYPERTROPHY, HEPATOCELLULAR. CENTRILOBULAR GALLBLADDER (GB) t -INFILTRATE, LYMPHOHISTIOCYTIC.-SLIGHT 727 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- . SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI ANIMAL NUMBER: 105512 SEX: MALE DOSE GROUP: 4 TERMINAL BODY WEIGHT: 22 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH; 184 STUDY WEEK OF DEATH: 27 RECORDER: TODD ACKER DATE AND TIME OF NECROPSY.- 02/25/99 9:21 PROSECTOR: STEVE VAN ADESTINE WEIGHER: TODD ACKER P-O-S-T--F-I-X---W-EI-G-H-ER-:---N-O-T--A-V-A-IL-A-B-LE------------------P-A-TH-O-L-OG-I-S-T:----R-O-BE-R-T---L-EE-D-L-E --------------------------------------- 0 B S E R V A T 1 0 N S (CONTINUED) HISTOPATHOLOGY NECROPSY --------------------------------------------- ---------------------------------------------------------------- THYMUS (TH) % -ATROPHY.-MODERATELY SEVERE LN, NESENTERIC (HS) - -HEMORRHAGE,-MINIMAL TRACHEA (Tit) : -INFILTRATE, LYMPHOHISTIOCYTIC.-SLIGHT -INFLAMMATION, ACUTE.-MINIMAL ADRENAL, CORTEX (AC) -DIFFUSELY DARK; ]BILATERAL: BROWN ADRENAL, CORTEX (AC) >UNREMARKABLE SALIV GL. MANDIB (SG) -INFILTRATE, LYMPHOHISTIOCYTIC,-MININAL JEJUNUM (JE) : -INFILTRATE, MACROPRAGE, PIONENTED.-BLIGHT KHMMARY, MALE (MM) : >SECTION EXAMINED; TISSUE NOT PRESENT PROSTATE (PR) : -INFLAMMATION, LYMPHOHISTIOCYTIC,-MININAL EPIDIT)YMIDES (EP) -HYPOSPERNIA,-SEVERE TESTIS (TE) i -IM14ATURE.-PRESENT GENERAL COMMENT (GC) -BONE NARROW SMEAR TAKEN - -E-YES- - -DAV-IDSO-NS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 728 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105512 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUSs SCHEDULED, TERMINAL SACRI TERMINAL BODY WRIGHT: 22 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH- 27 RECORDER: TODD ACKER DATE AND TIME OF NECROPSY: 02/25/99 9:21 PROSECTOR: STEVE VAN ADESTINE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T--A-V-A-IL-A-B-LE----------------------------------------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), NARROW, FEMUR (PH), NARROW, STERNUM (SE), BONE, STERNUM (SB), WE (EY). BRAIN (BR). KI LUNG (LU), HPART (HT), GALLBLADDER (GS). SPLEEN (SP), THYMUS (TH), LN, NESENTERIC (KS), TRACHEA (TR). ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI). SALIV GL, HAINDIB (SG), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST). DUODENUM (t)U),,PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECU14 (CE), COLA3N (CO), RECTUM (RE), SKIN (SX), MAMMARY, MALIS (MM), URINARY BLADDER (U]3), PROSTATE (PR). SEMINAL VESICLES (SV). EPIDIDYKIDES (EP). TESTI ADIPOSE TISSX3E (AT), LN, TRACHEOBRON (TB), LN, ANT KES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, STERMM (SE), BONE, STERNUM (SB), EYE (EY), KIDNEY (KD), LUNG (LU), HEART (HT), SPLEEN (SP), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (NA), AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC (SM), STONACHO GL (ST), DUODENUM (DU), PANCREAS ILEUM (IL), CECUM (CE), COLON (CO). RECTU14 (RE), SKIN (SK). URINARY BLADDER (US)o SEMINAL VESICLES (SV) --------------------------------------------------------------------------------------------------------- 729 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105530 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI TER14INAL BODY WEIGHT: 27 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 RECORDERT MICHELE ZINJ DATE AND T114E OF NECROPSY: 02/25/99 11:29 PROSECTOR: KEVIN BILLINGS PATHOLOGIST.- ROBERT LEEDLE WEIGHER: MICHELE ZIMA P-O-S-T--F-I-X-- W-E-I-GH-E-R-% ---N-OT-- A-V-A-IL-A-B-LE---------------------------------------------------------- --------------------- ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (t) -------- ORGAN TO BRAIN WEIGHT RATIO -------- 0R ST ---- ORGAN NAME ---------------------- -------- .0090 t .0041 WHIG LEFT ADRENAL (ADO) .2480 .0060 t .0027 WHIG RIGHT ADRENAL (ADl) .1640 60.5500 2.1978 % 1.0000 WRIG BRAIN (BR) LF KIDNEY (KDO) 5.6520 5.4770 .2052 % .1988 % .0933 .0905 WEIG WEIG RT KIDNEY (KD1) LIVER (LI) 49.1800 .1220 1.7851 % .0044 % .0046 % .8122 .0020 .0021 WEI WEIG WEIG LF OVARY RT OVARY (OVO) (OVI) .1280 .1542 % .0701 WHIG PANCREAS (PA) 4.2470 .2100 .0076 % .0035 WEIG LF THYROID/PARA RT THYROID/PARA (TTO) (TTi) .2150 .0078 t .0036 WRIG WRIG GALLBLADDER (GS) .59,10 -------B-I-L-E(-V-O-L-U-M-E-)----(-BI-)-----------------1-.2-0-0-0--m-L----------------------- ------------------------------------ 0 BS ERVA T 10N S HISTOPATHOLOGY NECROPSY ---------------------------------------------- ------------------------------------------------------------ BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-MINIMAL BRAIN (BR) : -INFILTRATE, MACROPRAGES, PIGMENTED, PERIVA KIDNEY (KD) : -GLO14ERULOSCLEROSIS,-KININAL LUNG (LU) -ADHESION(S); ALL LOBES TO EACH OTHER, PLLVM, PERICARDIAL SAC, AND R-AUDAL LOBES TO DIAPHRAGM: MULTIPLE RED, TAN, FIBROUS ADHESIONS; COLLECTED INTACT LUNG (LU) : -HYPERPt.ASIA. LYMPHOCYTIC, PERIBRONCHIOLAR/ MINIMAL -FIBROSIS. PLEURAL/SUBPLMML,-SLIGHT LIVER (LI) t -INFILTRATE, LYMPHOHISTIOCYTIC.-MINIMAL, HU 730 APPENDIX 5 Ccn individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOSiT_6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------ -------------------------- ANIMAL NUMBER: 105530 SEX: FEMALE STUDY DAY OF DEATH: DOSE GROUP: 1 SACRIFICE STATUS: 184 STUDY WEEK OF DEATH: 27 SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 2755.0 RECORDER: MICHELE ZINA DATE OF DEATH: 02/25/99 DATE AND TIME OF NECROPSY; 02/25/99 11:29 PROSECTOR: KEVIN BILLINGS WEIGHER: MICHELE ZINA PATHOLOGIST: ROBERT LEEDLE P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T --A-VA-I-L-AB-L-E-------------------------------------------------------------------------------------- 0 B S E R V A T 1 0 N S (CONTINUED) HISTOPATHOLOOY NECROPSY -------------------------------------------------- ---------------------------------------------------------------- TRACHEA (TR) : -INFILTRATE, LYMPHONISTIOCYTIC,-MINIMAL THYROID (TY) : -INFILTRATE, LYMPNOHISTIOCYTIC.-MININAL SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC.-MINIKAL MUSCLE, SKELETAL (SH) -DEGMiERATION,-SLIGHT -INFLAMMATION. GRANUL014ATOUS,-MODERATE -REGENERATION, 14YOFIBER,-HODERATELY SEVERE URINARY BLADDER (UB) -. -INFILTRATE, LYMPHOHISTIOCYTIC.-MINIMAL GENERAL COMMENT (GC) -BONE MARROW SHEAR TAKEN - -E-YES- -DAV-IDSO-NS - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - 731 APPENDIX 5 c Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105530 DATE OF DEATH: 02/25/99 SEX: FEMALE STUDY DAY OF DEATH: DOSE GROUP: I 184 STUDY WEEK SACRIFICE STATUS: OF DEATH: 27 SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHTI 2755.0 DATE AND TIME OF NECROPSY: 02/25/99 11:29 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZINA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZINA -------------------------------------------------------------------------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), NARROW, FEMUR (FM), NARROW, STERNUM (SE). BONE, STERNUM (SB), EYE (EY). BRAIN (HR), KIDNEY HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, NESENTERIC (MS), TRACHEA (TR). ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (UK), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA). JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE) SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA). CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHROBRON (TB), LN, ANT NES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXA141HATION: MARROW, FEMUR (FM), NARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), HEART (HT).' GALLBLADDER (GB), SPLEEN THYMUS (TH), LN, 14ESENTERIC (MS), ESOPHAGUS (ES). PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA ( AORTA (AO). PITUITARY (PI), SPINAL CORD (SC). NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENTIH (DU), PANCREAS JEJUNUM (JE), ILEUM (IL). CECU14 (CE). COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FE14ALE (HF), UTERUS (UT), OVARY (OV). VAGINA (VA), CERVIX (CV) --------------------------------------------------------------- ---------------------------------------------------- 732 Coi APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------- -------------- ------------------------------------- DOSE GROUP-. 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE ANIMAL NUMBER: 105531 DATE OF DEATH: 02/26/99 SEX: FEMALE STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY.WEIGHT-. 2625.0 RECORDER: JOHN S. HALFORD DATE AND TIME OF NECROPSY: 02/26/99 7:15 PR OSECTOR: STEVE VAN ADESTINE WEIGHER: JOHN S. HALFORD PATHOLOGISTI ROBERT LEEDLE P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T--A-VX-I-T-.-AB-L-E---------------------------------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE TO BODY WEIGHT (t) ORGAN'TO BRAIN WEIGHT RATIO -------- 0 RGA STA TU ORGAN NAME ---------------------- (GRAMS) -------- -------- .0043 WEIGHT T LEFT ADRENAL (ADO) .2360 .0090 % .0056 % .0027 WEIGHT RIGHT ADRENAL (ADI) .1480 2.0688 % 1.0000 WEIGHT BRAIN (BR) LF KIDNEY (KDO) 54.3050 4.3520 4.2910 .1658 t .1635 % % .0801 .0790 .7758 WEIGHT WEIGHT WEIGHT RT KIDNEY (KDI) LIVER (LI) 42.1310 1.6050 .0038 % .0018 WEIGHT LF OVARY (OVO) .0990 .0035 % .0017 WEIGHT RT OVARY PANCREAS (OV1) (PA) .0930 3.9080 .1970 .1489 % .0075 % % .0720 .0036 .0032 WEIGHT T WEIGHT WRIGHT LF THYROID/PARA RT THYROID/PARA .(rTO) (9rTl) .1740 .0066 WEIGHT GALLBLADDER (GB) .7250 - -------B-I-L-E(-V-O-L-U-M-E-)---(-B-I-)------------------1-.-8-0-00---mL----------------------------------------------------------------- 0B SB RVA T10N S HISTOPATHOLOGY NECROPSY ---------- --------------------------------------- ---------------------------------------------------------------MARROW, FEMUR (FH) - >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) i -INFILTRATE, MACROPHAGES, PIGMENTED, PERIVASCUIJ, KIDNEY (KD) : -INFILTRATE, LYMPHOHISTIOCYTIC.-SLIGHT LIVER (LI) -. -INFILTRATET LYMPHOHISTIOCYTIC.-MINIHAL, MULTI- ADRENAL, CORTEX (AC) -. -HYPERTROPHY, CORTICAL CELL,-KINIKHL JEJUNUM (JE) : -INFILTRATE, 14ACROPHAGE, PIGNMED,-MODERATE 733 APPENDIX 5 covi Individual Anatomic Pathology Data Terminal Sacrifice PAI 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS -------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105531 SEX% FEMALE STUDY DAY OF DEATH: DOSE 185 GROUP: 1 STUDY WEEK SACRIFICE STATUS: OF DEATH: 27 SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 2625.0 RECORDER-. JOHN S. HALFORD DATE OF DEATH: 02/26/99 PROSECTOR: STEVE VAN ADESTINE DATE AND TIME OF NECROPSYT 02/26/99 7:15 PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD P-O-S-T---FI-X---W-E-IG-H-E-R-: ---NO-T--A-V-A-I-LA-B-L-E-------------------------------------------------------------------------------------- ---------- 0 B S B R V A T 1 0 N S (CONTINUED) HISTOPATHOLOGY NECROPSY --------------------------------------------------- --------------------------------------------------------------- ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MINIMAL UTERUS (UT) : -AMYLOID,-SLIGHT GENERAL COMMENT (GC) -BONE NARROW SHEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - -- - - - - - - - - - - - - - - - - - - - -- - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSYT (BR), KIDNEY BONE, FEKEJR (FE), NARROW, FEMUR (FH), NARROW, STERNUM (SE), DONE, STERNUM (SB). EYE (BY), BRAIN LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GS), SPLEEN (SP), THYMUS (TH), LN. KESENTERIC (MS). TRACHEA (T ESOPHAGUS (ES). THYROID (TY), PARATHYROID (PT). ADRENAL, CORTEX (AC), ADRENAL, MEDULLA . (MA), AORTA (AO), PITUITARY (PI), SAILIV ",L, MANDIS (SG), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE SCIATIC (SN), STOMACH, GL (ST), I)UODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE). COLON (CO). RECTUM (RE). SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA). CERVIX (CV). ADIPOSE TISSUE (AT) , LN, TRACHEOBRON (TB), LN, ANT NES/PANC (AP) THE FBOOLNLEO,WINFGEMURTISS(UFEES), W1E4RAERROUWN,RESMTAERKRANBULME (SAET), MIBCORNOES,COPSITCERNUEMXAMI(NSABT)I,ON:EYE (EY), LUNG (LU), HEART (HT), GALLBLADDER (GB). SPLEEN (SP), THYMUS (TH), LN, NESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY). PARATHYROID (PT), ADRENAL, MEDULLA (14A), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SH), SPINAL CORD NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (IXJ), PANCREAS (PA), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (HP), URINARY BLADDER (UB). OVARY (OV), VAGINA (VA), CERVIX (CV) ----------------------------------------------------------------------------------------------------------------- 734 APPENDIX 5 covi individual Anatomic Pathology Data Terminal Sacrifice PAI 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------- ---------- ---------------------------------------------------------------- SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE ANIMAL NUMBER: 105535 SEX: FEMALE DOSE GROUP3 I STUDY WEEK OP DEATHI 27 TERMINAL BODY WEIGHT: 3270.0 G DATE OF DEATH% 02/26/99 STUDY DAY OF DEATH% 185 PROSECTOR: KEVIN BILLINGS RECORDERs MICHELE ZINA DATE AND TIME OF NECROPSY: 02/26/99 8:13 PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIKA P-O-S-T--P-I-X---WE-I-G-HE-R-:---N-OT---A-VA-I-L-A-BL-E-----------------------------------------------------O-R-G-A--N-----T-O--B-R-AI-N------------0--R--G--A--N -- ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT WEIGHT RATIO STA TU ---------- ORGAN NAME ---------------------- -------- -------- -------.0073 WEIGHT TA LEFT ADRENAL RIGHT ADRENAL (ADO) (ADl) .3770 .3150 51.9670 .0115 t .0096 t 1.5892 t .0061 1.0000 WEIGHT TA WEIGHT TM WEIGHT BRAIN (BR) LF KIDNEY (KDO) 6.6940 6.1930 .2047 t .1891 t 1288 :1190 1.2392 WEIGHT WEIGHT TAI RT KIDNEY (KD1) LIVER (LI) 64.3990 1.9694 % .0070 t 0044 WEIGHT LF OVARY RT OVARY (OVO) (OV1) .2280 .2100 5.0450 .0064 t .1543 % :0040 .0971 WEIGHT WEIGHT WEIGHT PANCREAS (PA) LF THYROID/PARA (TTO) .4660 .0143 % .0090 .0084 WEIGHII RT THYROID/PARA (TT1) .4370 .0134 % WRIGHT T GALLBLADDER (GB) .6970 BIL-E-(-V-O-L-U1-4-E-)---(-B-I-)----------------2-.-6-0-00---mL---------------------------------------------------------------------- 0B SBRV AT 10N S HIS"PATHOLOGY NECROPSY ----------- --------------------------------------- --------------------------------------------------------------NARROW, FEMUR (FM) : . >SECTION EXAMINED; TISSUE NOT PRESENT LUNG (LU) -ADHESION(S); PERICARDIAL ALL LOBES TO EACH OTHER, PLEURA, AND SAC-. MULTIPLE RED, TAN, FIBROUS ADHESIONS; LUNG (LU) : -FIBROSIS, PLEURAL/SUBPLEURAL,-SOMRB -FIBROSIS, INTERSTITIAL,-MODERATELY SEVERE COLLECTED INTACT LIVER (LI) -INFILTRATE, -VACUOLATION, LYMPHOHISTIOCYTIC,-MINIKAL, HEPATOCELLULAR.-MININAL, MULTIMULTI-FOCI SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT 735 Cov APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice P) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------- ---------------------------------------------------- SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE ANIMAL NUMBER: 105535 SEX: FEMALE DOSE GROUP: I STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3270.0 DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZINA DATE AND TIME OF NECROPSY: 02/26/99 8:13 . PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZINA P-O-S-T--F-I-X--W-E-I-G-HE-R-:---N-O-T --A-VA-I-L-AB-L-E--------------------------------------------------------------------------------------- 0 B S E RV A T 1 NECROPSY ---------------------------------------------------7-----------STOMACH, GL (ST) : -RED FOCUS (I) /AREA (S); 14UCOSA, FUNDIC: SINGLE RED FOCUS. 0.3 0 N S (CONTINUED) HISTOPATHOLOGY --------------------------------------------------- STOMACH, GL (ST) >UNREMARKABLE KH IN DIAMETER; FOCUS HAS A STELLATE PATTERN >NOTE:>FUNDIC MUCOSA, ALONG GREATER CURVATURE: SINGLE APPARENT HOOK WORM EMBEDDED INTO MUCOSA, 3.0 x 0.1 x 0.1 cm DUODENUM (DU) -INFILTRATE, MACROPHAGE, PIGKENTED.-HODERATE JEJUNUH (JE) : -INFILTRATE, MACROPRAGE, PIGNMUED.-HODERATE ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MODERATE CECUM (CE) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT MAMMARY, FEMALE IMF) : -INFLAMMATION, ACUTE,-MINIMAL URINARY BLADDER (UB) : -INFILTRATE, LYMPHOHISTIOCYTIC.-MININAL UTERUS (UT) : -ANYLOID,-SLIGHT GENERAL COMM M (GC) -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) t >NOTE:>ANINAL APPEARS TO B-E I-N E-STRO-US - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - 736 APPENDIX 5 c Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNONO.E.GUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105535 SEX: FE14ALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 3270.0 DATE OF DEATHT 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATHT 27 RECORDER: MICHELE ZINA DATE AND TIME OF NECROPSY: 02/26/99 8:13 PROSECTOR: KEVIN BILLINGS WEIGHER: MICHELE ZINA POST-FIX WEIGHERZ NOT AVAILABLE PATHOLOGISTT ROBERT LEEDLE --------------------------------------------------------------- --------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY% BONE, FEMUR (FE), KHRROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (BY), BRAIN (SR), KIDNEY HEART (HT). LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, NESENTERIC (KS), TRACHEA (TR). ESOPHAGUS (ES). THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC). ADRENAL, MEDULLA (14A), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SH). SPINAL CORD (SC). NERVE, SCIATIC (SN), DUODENUM PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE). COLON (CO), RECTUM (RE), SKIN (SK). MAMMARY, FEMALE (MF) URINARY BLADDER (UB), UTERUS (UT), OVARY (OV). VAGINA (VA). CERVIX (CV), ADIPOSE TISSUE (AT). LN, TRACHEOBRON LN, ANT NES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATIONT BONE, FEMUR (FE), MARROW, STERNUM (SE), DONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, 14ESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC). ADRENAL, MEDULLA (MA). AORTA (AO). PITUITARY (PI). MUSCLE, SKELETAL SPINAL CORD (SC), NERVE, SCIATIC (SH), PANCREAS (PA), COLON (CO), RECTUM (RE), SKIN (SK), OVARY (OV), VAGINA CERVIX (CV) ------------------------------------------- ------------------------------------------------------------------------ 737 APPENDIX 5 Cov Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFI.UOROOCTAKE SUIJ?ONIC ACID POTASSIUM---S-A-L-T--(-P-P-OS-;-T--6-2-9-5-) ---I-N--CY-N-O-M-OI-G-U-S---M-O-NK-E-Y-S------------------------------------------------------------------------------ DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE ANI14AL NUMBER: 105544 SEX- FEMALE STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2635.0 C@ DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 PROSECTOR: KEVIN BILLINGS RECORDERT MICHELE ZlKh DATE AND TIME OF NECROPSY-. 02/25/99 9:55 PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZINA P-O-S-T--F-I-X--W-E-I-GH-E-R-: ---N-OT---AV-A-3-1L-A-B-LE------------ ---------------------------------- --------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0 RG A S TATU ORGAN NAME (GRAMS) TO BODY WEIGHT (t) -------- WEIGHT RATIO -------- --------- ---------------------- -------- .0118 t .0052 WEIGHT TAI LEFT ADRENAL (ADO) .3120 .2440 .0093 % .0041 WRIGHT RIGHT ADRENAL BRAIN (BR) (AD3.) 59.7410 5.3110 2.2672 % .2016 % 1.0000 .0889 .0878 WEIGHT WEIGHT WEIGHT TA LF KIDNEY (KDO) RT KIDNEY (KDI), 5.2470 .1991 % 1.8467 t .8145 WEIGHT LIVER (LI) LF OVARY (OVO) 48.6600 .2260 .1380 .0086 % .0052 % .0038 .0023 WEIGHT T WEIGHT TA RT OVARY (ovi) .1711 % .0755 WEIGHT TA PANCREAS (PA) 4.5080 .1540 .0058 % .0026 WEIGHT LF THYROID/PARA RT THYROID/PARA (TTO) (TT1) .1560 .0059 % .0026 WEIGHT WEIGHT GALLBLADDER (GB) .3810 BILE(VOLUME) (BI) 2.2000 ML 7 --------- ------------- --------------------------------------------------------------------------------------------- 0 B S E R V A T 10 N S HISTOPATHOLOGY NECROPSY -------------------------------------------------- ---------------------------------------------------------------- HARROW, STERNUM (SE) : -HYPOCELLULAR.HARROW,-SLIGHT BRAIN (BR) : -INFILTRATE, MACROPHAGES, PIGMENTED, PERIVASCULAJ LIVER (LI) -LIGHT FOCUS (1) /AREA(S) ; TRIM COMMENT: DIAPHRAGMATIC SURFACE LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC.-MINIKAL,-HULTI- OF LEFT LATERAL LOBE: SINGLE TAN AREA, 1.0 CH IN DIAMETER; SUBMITTED ON ROUTINE SECTION GALLBLADDER (GB) -INFILTRATE, LYMPHOHISTIOCYTIC.-MINIMAL LN, MESENTERIC (HS) I -INFILTRATE, HACROPHAGE, PIGNENTED,-MODERATE 738 APPENDIX 5 Cov Individual Anatomic Pathology Data Terminal Sacrifice PA 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------ --------------------------------------- ANIMAL NUMBER: 105544 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT- 2635.0 G DATE OF DEATH. 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 RBCORDER. MICHELE ZIKA DATE AND TIME OF NECROPSY: 02/25/99 9:55 PROSECTOR: KEVIN BILLINGS WEIGHER: MICHELE ZINA P-O-S-T--F-I-X--W-E-I-GH-E-R-:---N-OT---AV-A-I-R-.A-B-L-E -----------------P-AT-H-O-LO-G-I-ST------RO-B-E-RT---L-E-E-DL-E--------------------------------------------- 0 B S B R V A T 1 0 N S (CONTINUED) HISTOPATHOLOGY NECROPSY --------------------------------------------------- --------------------------------------------------------------- TRACHEA (TR) i -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT ESOPHAGUS (ES) I -INFILTRATE, LYMPHOHISTIOCYTIC,-NINIMAL PARATHYROID (PT) >SECTION EXAMINED; TISSUE NOT PRESENT MUSCLE, SKELETAL (SH) ; -PARASITES, CYST,-PRESENT >NOTE::-HEAVY BURDEN, SARCOCYST-LIKE. DUODENUM (DU) : -INFILTRATE, MACROP*TAGE, PIGMENTED,-SLIGHT JEJUNUM (JE) : -INFILTRATE, MACROPRAGE, PIGMENTED,-SLIGHT ILEUM (IL) i -INPILTRATE, KACROPHAGE, PIGHWURD.-SLIGHT MAMMARY, FEMALE (MF) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT URINARY BLADDER (UB) : -INFILTRATE. LYMPHOHISTIOCYTIC,-SLIGHT OVARY (OV) : -MINERALIZATION,-MODERATE GENERAL COMMENT (GC) -BONE MARROW SHEAR TAKEN - -E-YES- -I)A-VIDS-ONS - - - --- - - - - - - -- - -- - - - - - - - - - - - - - - - - - 739 APPENDIX 5 cov IndividualAnatomic PathologyData Terminal Sacrifice pp 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC --------------------------------A-C-ID--P-OT-A-S-SI-U-M--S-A-L-T -(-P-F-OS-;-T--6-2-9-5)---IN--C-YN-O-N-OL-G-U-S--M-ON-K-E-Y-S-------------------------------------- ANIMAL NUMBER; 105544 SEX: FEMALE DOSE GROUPS I SACRIFICE STATUS: SCHEDULED. TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 2635.0 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 RECORDER: MICHELE ZINA DATE AND TIME OF NECROPSY: 02/25/99 9:55 PROSECTOR: KEVIN BILLINGS PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZINA PO-S-T--F-I-X--WE-I-G-HE--R--: --NO-T--A-VA-I-L-AB-L-E------------------------------------------------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSYT BONE, FEMUR (FE). MARROW, FEMUR (FM), NARROW, STERMW (SE), BONE, STERNUM (SB), EYE (BY), BRAIN (BR), KIDMff LUNG (LU). HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH). LN, NESENTERIC (NS). TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (14A),AORTA (AO), PITUITARY (PI). SALIV GL, MANDID (SG), MUSCLE, SKELETAL (SH). SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JR), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE). SKIN (SK), MAMMARY, FEMALE (KF). URINARY BLADDER (UB), UTERUS (UT). OVARY (OV), VAGINA (VA), CERVIX (CV)l ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT'NES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMMLE BONE, FEMUR (FE), MARROW, FEMUR AT MICROSCOPIC EXAMINATIONS (FN), BONE, STERNUM (SB), EYE (BY), KIDNEY (KD), LUNG (LU), HEART (HT), SPLEEN (SP), THYMUS (TH), THYROID (TY), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (14A),AORTA (AO), PITUITARY (PI SALIV GL, MANDIB (SG). SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), PANCREAS (PA), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SX), UTERUS (UT). VAGINA (VA), CERVIX (CV) -------------------------------------------------------------------------------------------------------------------- 740 Cov@ APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice PA 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SMFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------------------------- SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE ANIMAL NUMBER: 105537 SEXT FEMALE DOSE GROUP: 2 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WRIGHT: 4055.0 G *RECORDER: TODD ACKER DATE OF DEATH: 02/25/99 PROSECTOR: STEVE VAN ADESTINE DATE AND TIME OF NECROPSY: 02/25/99 7:31 PATHOLOGISTs ROBERT LEEDLE WEIGHER: TODD ACKER POST-FIX WEIGHER: NOT AVA:ELA-BL-E------------------------------------------------------------------------------------- -------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0 R0Ai ORGAN NAME (GRAMS) TO BODY WEIGHT (t) -------- WEIGHT RATIO -------- STA TU --------- ---------------------LEFT ADRENAL (ADO) -------.3730 .0092 % .0075 % .0061 .0049 WRIGHT WEIGHT RIGHT ADRENAL BRAIN (BR) (ADI) .3030 61.3750 7.0240 1.5136 t .1732 % 1.0000 .1144 WEIGHT WRIGHT LF KIDNEY RT KIDNEY (KDO) (KD1) 6.6650 .1644 % 1.8548 t .1086 li2255 .0045 WEIGHT WEIGHT WEIGHT LIVER (LI) LP OVARY (OVO) 75.2140 .2790 .0069 % .0056 % .0037 WEIGHT RT OVARY PANCREAS (CV1) (PA) .2280 6.1370 .3200 .1513 % .0079 % .1000 .0052 WEIGHT WRIGHT LP THYROID/PARA (TTO) .3400 .0084 % .0055 WEIGHT RT THYROID/PARA (TT1) WEIGHT GALLBLADDER (GB) .5100 -------B-I-L-E-(V-O-L-U-M-E-)----(B-I-)-----------------3-.-00-0-0--M-L----------------------------------------------------------------------- 0 BS ERV AT 10N S HISTOPATHOLOGY NECROPSY -------------------------------------------------- --------------------------------------------------------------- GENERAL COMMENT (GC) : -BONE NARROW SMEAR TAKIEN -EYES - DAVIDSONS - -A-NIMA-L -OBE-SE - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 741 APPENDIX 5 Co Individual Anatomic Pathology Data Terminal Sacrifice p 26-WEEK CAPSULE TOXICITY STUDY WITH PMTFLUOROOCTA.NE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105537 SEX: FEMALE @ DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 405S.0 DATE AND TIME OF NECROPSY: 02/25/99 7:31 PROSECTOR: STEVE VAN ADESTINE RECORDER. TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ---------------------------------------------------------------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN NA14E ---------------------- (GRAMS) -------- ORGAN WEIGHT RELATIVE TO BODY WEIGHT -------- ORGAN 70 BRAIN WRIGHT RATIO -------- 0 RGA STA TU --------- LEFT ADRENAL (ADO) .3730 .0092 % .0061 WEIGHT TA RIGHT ADRENAL (At)l .3030 .0075 t .0049 WEIGHT BRAIN (DR) 61.3750 l.Sl36 t 1.0000 WEIGHT TA LF KIDNEY (KDO) 7.0240 .1732 t .1244 WEIGHT TA RT KIDNEY (KDll 6.66so .1644 t .1086 WEIGHT TA LIVER (LI) 7S.2140 1.8548 % 1.2255 WEIGHT LF OVARY (OVO) .2790 .0069 % .0045 WEIGHT TA RT OVARY (OV1) .2280 .0056 t .0037 WEIGHT PANCREAS (PA) 6.1370 .1513 t .1000 WEIGHT TA LF THYROID/PARA (TTO) .3200 .0079 % .0052 WEICHT RT THYROID/PARA (TT1) .3400 .0084 % .0055 WEIGHT --------------------------------------------------------------------------------------------------------------------- OBSERVATIONS NECROPSY HI M PATHOLOGY ------------------------------------------------------------------------------------------------------------------- LIVER (LI) : -NWILTRATE, LYMPHOHIMOCYTIC,-MINIMAL, MULTI-PO THYMUS (TH) : I -ATROPHY,-M]:NIMAL SPINAL CORD ISC) : -PIGMENT, NEURONAL,-SLIGHT GENERAL COMMENT (CC) -BONE MARROW SMEAR TAXIEN -EYES - DAVIDSONS -ANIMAL OBESE GENERAL INFORMATION >NOTE; >GALLBLADDER (XX) WEIGHT IS 0.5100 GRAMS BILE VOLUME IS 3.0000 ML - - - - - - - - - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - APPENDIX S c Individual Anatomic Pathology Data Terminal Sacrifice p 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLCUS MONKEYS ---------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: IOSS37 DATE OF DEATH: 02/25/99 DATE AND TIME OF NECROPSY: SEX: FEMALE STUDY DAY OF 02/25/99 7:31 DOSE GROUP; 2 DEATH: 184 STUDY WEEK PROSECTOR: STEVE VAN SACRIFICE OF DEATH: ADESTIM STATUS: 27 SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WRIGHT: 405S.0 RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ---------------------------------------------------------------------------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY-. BONE, FEMUR (FE), NARROW, FEMUR (FM), NARROW, STERNUM (SE), DONE, STERNUM ISB), EYE (EY), BRAIN (BR), KIDNEY LUNG (LU), HEART (HT), LIVER (LI)o GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA ESOPHAGUS (ES), THYROID (TY), PARATHYROID IPT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SO), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC ISN), STOMACH, CL IST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JR), ILEUM IIL), CECUM (CE), COLON (CO). RECTUM (RE), SKIN (SX). MAMMARY, FEMALE (HP), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA IVA), CERVIX (CV), ADIPOSE TISSUE (AT). t.M.7RACHEOBRON (TS), LN, AM MES/PANC (AP) ---------------------------------------------------------------------------------------------------------------------- APPENDIX 5 Co Individual Anatomic Pathology Data Terminal Sacrifice p 26-wEEK CAPSULE mXlciTY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT IPPOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105541 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH- 27 TMU4INAL BODY WEIGHT: 2510.0 DATE AND TIME OP NECROPSY. 02/26/99 9:47 PROSE M R: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILHBLE PATHOLOGIST: ROBERT LEZDLE WEIGHER: JOHN S. HALFORD ---------------------------------------------------------------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN To BRAIN 0 RCA ORGAN NAME ---------------------- (GRAMS) -------- TO BODY WEIGHT -------- WEIGHT RATIO -------- STATU --------- LEFT ADRENAL (ADO) .4170 .0166 t .0066 WEIGHT TA RIGHT ADRENAL (AMl) .3060 .0122 % .0048 WEIGHT BRAIN (BR) 63.2760 2.5210 % 1.0000 WEIGHT TA LF KIDNEY (KDO) 4.9450 .1970 % .0781 WEIGHT RT KIDNEY IKD1) 4.6880 .1868 % .0741 WEIGHT LIVER (LI) 47.6610 1.8988 % .7532 WEIGHT LF OVARY (OVO) .1240 .0049 % .0020 WEIGHT RT OVARY (OV1) .1570 .0063 % .0025 WEIGHT PANCREAS (PA) 5.0750 .2022 % .0802 WEIGHT T) LF THYROID/PARA (TTO) .2130 .0085 % .0034 WEIGHT RT THYROID/PARA (7?1) .2300 .0092 % .0036 WEIGHT ---------------------------------------------------------------------------------------------------------------------- 0B S8RVAT 10N S NECROPSY HISTOPATHOLOGY ------------------------------------------------------------------------------------------------------------------- LUNG (LU) -ADHESION(S); RIGHT AIND LEFT CAUDAL LOBES AND LEFT INTERMEDIATE LOBE TO 131APHRAGN: MULTIPLE TAN, FIBROUS ADHESIONS; COLLECTED INTACT -DARK FOCUS (1) /AREA (S) ; ALL LOBES: MULTIPLE DARK BROWN AREAS, PINPOINT AND UP To 0.7 X 0.4 cm LIVER (LI) ; -ADHESIONIS); DIAPHRAGMATIC SURFACE OF RIGHT LATERAL LOBE TO SURROUNDING RESENTERY, ALONG MARGIN: MULTIPLE TAN, FIBROUS ADHESIONS (CAP 29) LUNG (LU) >NOT REQUIRED TO BE EXAMINED FOR ANIMAL LIVER (LI) -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIKhL, THYMUS (TH) -ATROPHY,-MOD M TE SPINAL CORD (SC) : -PIGMENT, NEURONAL,-NODERATE MULTI- APPENDIX 5 c Individual Anatomic PathOlOgY Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUORoocTANE SULFONIC -------------------------------------AC-I-D--P-O-TA-S-S-IU-M---S-A-L-T --I-P-F-OS-;-T--6-2-9-5)----I-N--CY-IN-O-MO-L-O-US----MO-N-K-E-YS-------------------------- ANIMAL HUMBER: 105541 DATE OF DEATH: 02/26/99 DATE AND TIME OF NECROPSY: SEX: FEMALE DOSE GROUP. 2 STUDY DAY OF DEATH: 185 STUDY WEEK 02/26/99 9.47 PROSECTOR-. STEVE VAN SACRIFICE OF DEATH: ADESTINE STATUS: 27 SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 2510.0 RECORDER: JOHN S. MALFORD POST-FIX WEIGHER: NOT AVHXLABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD -------------------------------------------------------------------------------------------------------------------- 0 B 9 E R V A T 1 0 N S (CONTINUED) NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------------------------------------------------------- GENERAL COMMENT (CC) : -BONE MARROW SHEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION IXX) >NOTE: >GALLBLADDER WEIGHT IS 0,5260 GRAMS BILE VOLUME IS 1.0000 HL - - - - - - - -- --- -- - -- - - - -- - - - - - - - -- - - - -- - - - THE FOLLOWING ORGANS WERE UNREQARKABLE AT NECROPSY: BONE, FEMUR IFE), TU.MOW, FEMUR IFM), NARROW, STERNUM (SE), BONE, STERNUM (SB). EYE (EY). BRAIN IBR), KIDNEY HEART (HT), GALLBL.ADDER (GB), SPLEEN ISP), THYMUS (TH), LN, NESENTERIC INS), TRACHEA (TR), ESOPHAGUS (ES). THYROID (TY),' PAI;tA7HYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA INA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST). DUODENUM (DU), PANCMAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER IUB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE LN, TRACHEORRON (TB), LN, ANT NES/PANC (AP) -------------------------------------------------------------------------------------------------------------------- APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAWE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLCUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105547 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 25 DATE AND TIME OF NECROPSY: 02/26/99 9:20 PROSECTOR.- STEVE VAN ADESTINE RECORDER: JOHN S. HAL POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALF ------------------------------------7-------------- ------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0R ORGAN NAME ---------------------- (GRAMS) -------- TO 13ODY WEIGHT (t) -------- WEIGHT RHTIO -------- ST ---- LEFT ADRENAL (ADO) RIGHT ADRENAL. (ADl) BRAIN (BR) LF KIR)N" (KDO) .3130 .2300 60.8690 5.4180 .0122 t .0089 t 2.3684 % .2108 t .0051 .0038 1.0000 .0890 WEIG WEIG WEIG WEIG RT Klr)NEY (KD1) 5.5840 .2173 t .0917 WEIG LIVER (LI) 49.9520 1.9437 t .8206 WEIG LF OVARY (OVO) .1590 .0062 t .0026 WEIG RT OVARY (OVI) .2030 .0079 % .0033 WEIG PANCREAS (PA) 5.1480 .2003 % .0846 WEIG LP THYROID/PAM (ITO) .1550 .0060 t .0025 WEIG RT THYROID/PAftA (TT1) .1410 .0055 ik .0023 WEIG ----------------------------------------------------------------------------------------------------------------- 0 B SE RV A T 1 0 N S NECROPSY HISWPATHOLOGY -------------------------------------------------------------------------------------------------------------- LUNG (LU) : -ADHESION(S); LEFT CAUDAL LOSE TO DIAPHRAGM.: MULTIPLE TAX, LUNG ILU) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL FIBROUS A13HESIONS; COLLECTED INTACT -DARK FOCUS (1) /AR]EA (S) ; ALL LOBES: MULTIPLE AREAS, PINPOINT AND UP TO 0.5 X 0.3 CM DARK BROWN LIVER (LI) -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, 14U THYMUS (Tli) t -CYST,-PRESENT -ATROPHY,-SLIGHT GENERAL COMMENT (GC) -BONE NARROW SHEAR TAKEN -EYES - DA%VIDSONS APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT IPFOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBERT JOSS47 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIF DATE OF DEATH: 02/26/99 STUDY DAY OF DRATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 257 DATE AND TIME OF NECROPSY: 02/26/99 9:20 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALF POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFO ------------------------------------------------------------------------------------------------------------------ 0 B S E R V A T 1 0 N S ICONTINUED) NECROPSY HISTOPATHOLOGY --------------------------------------------------------------------------------------------------------------- GENERAL INFORMATION >NOTE: >GALLBLADDER (XXI : WEIGHT IS 0.5390 CRAMS BILE VOLUME IS 1.2000 ML - - - - - - - -- -- - - -- - - - -- - - - - - -- - - - - - - -- - -- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, PENUR (FE), MARROW, FEMUR (FM), NARROW, STERNUM (SE), DONE, STERNUM (SBI, EYE (LPY). BRAIN (OR), KIDN HEART IHT), LIVER (LI). GALLBLADDER JOB),, SPLEEN (SP). THYMUS ITH), LN, NESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID ITY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (KA), AORTA (AOI. PITUITARY (PI), SALIV GL, MANDIB (SO), KUSCLE, SKELETAL ISM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA). JEJUNUM (JE), ILEUM JIL), CECUM (CE), COLON (CO), RECTUM SKIN ISK), MAMMARY, FEMALE (HF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREKARKABLE AT MICROSCOPIC EXAMINATIONSPINAL CORD ISC) ------------------------------------------------------------------------------------------------------------------ APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUORGOCTAME SULFONIC ACID POTASSIUM SALT IPPOS;T-6295) IN CYNOMOLGUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER. 105550 SEX: FEMHLE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL 13ODY WEIGHT: 29 DATE AND TIME OF NECIROPSY: 02/26/99 6:43 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZI POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGM: ROBERT LEEDLE WEIGHER: MICHELE ZIM) ----------------------------------------------------------------------------------------------------------------- ORGAN NAME ---------------------- ABSOLUTE ORGAN WRIGHT (GRAMS) -------- ORGAN WEIGHT RET@ATM TO BODY WEIGHT -------- oRcAN To BRAIN WEIGHT RATIO -------- 0 ST ---- LEFT ADRENAL (ADO) .4230 .0150 .0074 WEI RIGHT ADRENAL (ADI 1 .,2680 .0095 .0047 WEI BRAIN (ER) S6. 9130 2.0182 1.0000 WEI LF KIDNEY (KX)O) 6.0900 .2160 .1070 WEI RT KIDNEY IKT)L) 6.1soo .2191 .1081 WEI LIVER (LI) 54.4840 1.9321 .9573 WEI LF OVARY (OVO) .1270 .0045 .0022 WPl RT OVARY (071) .1270 .0045 .0022 WEI PANCREAS (PA) 7.2830 .2583 .1280 WEI LF THYROID/PARA (TTO) .1670 .0059 .0029 WEI RT THYROID/PA.RA (Trl) .2290 .0081 .0040 WEI ---------------------------------------------------------------------------------------------------------------- 0B 9BRVAT 10N S NECROPSY HISWPATHOLOGY ------------------------------------------------------------------------------------------------------------- LUNG (LU) : -ADHESION(S); SAC, CAUDAL ALL LOBES LOBES TO EACH OTHER, PLEURA, PERICARDIAL TO DIAPHRAGM: MULTIPLE RED, TAN, FIBROUS LUNG ILU) : >NOT REQUIRED TO BE EXHMINED FOR ANIMAL ADHESIONS; COLLECTED INTACT LIVER (LI) -INFILTRATE, -VACUOLATION, LYKPHOHISTIOCYTIC.-MINIMAL, HEPATOCELLULAR,-SLIGHT, HU MULTI THYMUS (TH) : -ATROPHY,-MINIMAL SPINAL CORD (SC) : -PIGMENT, NEURONAL,-SLIGHT GENERAL -BONE -EYES COMMENT (GC) KARROW SHEAR TAKEN - DAVIDSONS APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PE"LUOROOCTAKE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLCUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: IOS5SO SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCNEDULED, TERMINAL SACRI DATE OF DEATH: 02/26199 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 DATE AND TIME OF NECROPSY- 02/26/99 6:43 PROSECWR: KEVIN BILLINGS TERMINAL BODY WEIGHT: 28 RECORDER: MICHELE ZIK POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ----------------------------------------------------------------------------------------------------------------- 0 B S E R V A T 1 0 N S (CONTINUED) NECROPSY HISWPATHOLC>GY -------------------------------------------------------------------------------------------------------------- GENERAL INFORMATION >NOTE: >GALLBLADDER (XX) : WEIGHT IS 0.6200 GRAMS BILE VOLUME IS 1.2000 ML - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -; - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY-. BONE, FE14UR (FE), KARROW, FEMUR (FH), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR). KI HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THY14US (TH), LN, MRSENTERIC (MS), TRACHEA (TRI, ESOPHAGUS (ES), THYROID (TY), PARHTHYROID (PT), ADRENAL, CORTEX (AC). ADRENAL, MEDULLA (KA). AORTA (AO), PITUITARY (PI), SALIV GL. MANDIB (S(;),MUSCLE, SKEtZrAL (SH), SPINAL CORD (SC), NLFRVEI SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL). CECUM (CE), COLON (CO), RECTUM SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TS), LM, ANT MES/PANC ("I ----------------------------------------------------------------------------------------------------------------- APPENDIX 5 individual Anatomic Pathology Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PMWLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLCUS MONKEYS ------ --------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: IOSS32 SEX: FEMALE STUDY DAY OF DEATH. DosE GROUP: 3 184 STUDY WEEK SACRIFICE STATUS: OF DEATH- 27 SCHEDULED, TERMINAL SACR TERMINAL BODY WEIGHT: 2 RECORDER: MICHELE ZI DATE OF DEATH: 02/25/99 DATE AND TIME OF RIECROPSY: 02/25/99 6:47 PROSECTOR: KEVIN BILLINGS POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIK --------------------------------------------------------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELAT M TO BODY WEIGHT -------- ORGAN TO BRAIN WEIGHT RATIO -------- 0 ST --- ORCAU NAME ---------------------- -------- .0127 % .0054 WEI LEFT ADRENAT, RIGHT ADRENAL (ADO) (ADl) .3230 .2160 ooss % 2.3622 t .0036 WEI 1.0000 WEI BRAIN (BR) LF KIDNEY (KDO) 60.2360 5.0310 4.9920 .1973 % .1958 % .0835 WEI .0829 WEI WEI RT KIDNEY (KDll LIVER (LI) 59.3190 2.2870 t .0025 t .9682 .0010 WEI LF OVARY RT OVARY IOVO) (OVI) .0630 .0870 .0034 t .1768 t .0014 WEI .0749 WEI PANCREAS (PA) LF THYROID/PARA (TTO) 4.5080 .1150 .0045 % .0019 WEI WEI RT THYROID/ PARA (TT1) .1020 .0040 t .0017 --------------------------------------------------------------------------------------------------------------- 029B RVAT 10N 9 HISMPATHOLOC;Y ----- ---------------------N-E-C-R-O-P-S-Y---------------------------------- ---------------------------------------- LUNG (LU) : -RED FOCUS (I) /AP-EA(S); ALL LOBES: 14ULTIPLE DARK RED PINPOINT LUNG ILU) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL FOCI THYMUS (TH) -ATROPHY,-SEVERE SPINAL CORD (SC) -PIGMENT, NEURONAL,-MODLPRATE GENERAL COMMENT (CC) -BONE NARROW SKF-AR TAKEN -EYES - DAVIDSONS GENERAL INFOPXATIC)N >NOTE: >GALLBLA]3t)ER OCK) WEIGHT 1.2000 KL - - - - - - --- 19 0.4650 GRAMS BILE VOLUME IS -- - - - -- - -- - - - -- - - - - -- - - - - - - APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLCUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: IOS532 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 . STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 25 DATE AND TIME OF NECIROPSY: 02/25/99 6:47 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZI POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER:-MICHELE-ZIM) ---------------------------------------------------------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), NARROW, FEMUR (FM), HARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR). KI HEART (HT), LIVER (LI), GALLBLADDER (GB). SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (IES), THYROID (TY), PARATHYROXI) (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA). AORTA (AO). PITUITARY (PI), SALIV OL, MANDIB (SC), MUSCLE, SKELETAL ISM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (ILI, CECUM (CE), COLON (CO), RECTUM SKIN (SK), K"KARY, FEMALE (MF), URINARY BLADDER (UR), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV) ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT KES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: LIVER ILI) ---------------------------------------------------------------------------------------------------------------- APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLCUS MONKEYS ------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: ZOSS38 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIF DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 320 DATE AND TIME OF NECROPSY: 02/25/99 10:25 PROSECTOR- STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER- TODD ACKER ------------------------------------------------------------------------------------------------------------------ ORGAN NA14E ---------------------- ABSOLUTE ORGAN WEIGHT (GRAMS) -------- ORGAN WEIGHT RELATIVE TO BODY WEIGHT -------- ORGAN TO BRAIN WEIGHT RATIO -------- 0R ST ----- LEFT ADRENAL (ADO) .3850 .0120 t .0069 WEIG RIGHT ADRENAL (ADl) .2630 .0082 % .0047 WEIGI BRAIN (BR) 55.6900 1.7403 % 1.0000 WEIG LF KIDNEY (KDO) 5.8390 .1825 % .1048 WEIG RT KIDNEY (KDll 5.3480 .1671 t .0960 WEIG LIVER (LI) S9.s7go 1.8618 % 1.0698 WRIG LF OVARY (OVO) .2420 .0076 t .0043 WEIG RT OVARY (OV1) .1690 .0053 % .0030 WEIG PANCREAS (PA) 4.6070 .1502 % .0963 WEIG LP THYROID/PARA (TTO) .1350 .0042 t .0024 WEIG RT THYROID/PARA (TT1) .1480 .0046 % .0027 WEIC ---------------------------------------------------------------------------------------------------------------- 0 B S'E R V A T 1 0 N S NECROPSY HISWPATHOLOGY ------------------------------------------------------------------------------------------------------------- LUNG (LU) : - -DARK FOCUS (1) /ARP-A (S); ALL LOBES, DIFFUSE: MULTIPLE BLACK LUNG (LU) : >NOT REQUIRED To BE EXAMINED FOR ANIMAL PINPOINT FOCI LIVER (LI) -INFILTRATE, LYMPHOHISTIOCYTIC.-MININAL, MU SPLEEN (SP) -LIGHT FOCUS (I) /AREA (S); DIFFUSE: MULTIPLE GRAY AREAS, UP TO SPLEEN (SP) : >NOT REQUIRED TO BE EXAMIM FOR ANIKAL 1.2 X 0.7 cm THYMUS (TH) -ATROPHY,-SLIGHT SPINAL CORD (SC) -PIGMENT, NRURONAL.-MINIMAL CECUM (CE) : >NOT REQUIRED To BE EXAMINED FOR ANIMAL APPENDIX 5 Individual Anatomic Pathology Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULPONIC ACID POTASSIUM SALT (PPOS;T-629S) IN CYMOMOLOUS MONKEYS ---------------------------------------- 7 ------------------------------------------------------------------------ ANIMAL NUMBER: 105538 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH-. 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 32 DATE AND TIME OF NECROPSY: 02/25/99 10:2S PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NO*r AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ----------------------------------------------------------------------------------------------------------------- 0 B S E R V A T 1 0 N S (CONTINUED) NECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- CECUM (CE) : -RED FOCUS (I)/AREA (S); SEROSAL SURFACE: MULTIPLE DARK RED FOCI, UP To 0.5 CM IN DIAMETER, COLLECTED ON ROUTINE SECTION GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) >NOTE: >CALLBLADDEFT WEIGHT IS 0.5060 CRAMS BILE VOLUME 10 1.6000 ML - - -- - - - --- - - - -- - - -- - - -- -- - - - - -- - -- - - -- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: DONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SEI, BONE, STERNUM (SB), EYE IEY), BRAIN (BR). KI HEART (HT), LIVER ILI), GALLBLADDER (GB), THYMUS (TH), LN, MESMNSRIC (NS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY) . PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AOI, PITUITARY (PI) SALIV GL, MANNDIB (SG), MUSCLE, SKELETAL ISM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, CL (ST). DUODENUM (DU) . PANCREAS (PA), JEJUNU" (JE), ILEUM (IL), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEIU URINARY BLADDER (UB), UTERUS (UT). OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHBO -------L-N-,--A-NT--M-E-S-/-PA-N-C--(-A-P-)---------------------------------------------------------------------------------------- APPENDIX S Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105545 DATE OF DEATH: 02/25/99 DATE AND TIME OF NECROPSY: SEX: FEMALE DOSE GROUP: 3 SACRIFICE STUDY DAY OF DEATH: 184 $"MY WEEK OF DEATH: 02/25/99 7:31 PROSECTOR: KEVIN BILLINGS STATUS: 27 SCHEDULED, TERMINAL SACR TERMINAL BODY WEIGHT: 2 RECORDER: MICHELE ZI POST-FIX WEIGHER: NOT AVAILABLE PATHOLOG M : ROBERT LEEDLE WEIGHER: MICHELE ZIR --------------------------------------------------------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0 ORGAN NAME (GRAMS) TO BODY WEIGHT (t) WEIGHT RATIO ST ---------------------- -------- -------- -------- --- LEFT ADRENAL (ADO) .2640 .0107 % .0047 WEI RIGHT ADRENAL. (ADl) .2060 .0084 % .0037 WEI BRAIN (BRI 55.6590 2.2626 t 1.0000 WEI LF KIDNEY (IKDO) 5.4870 .2230 t .0986 WEI RT KIDNEY (IKD1) 5.2040 .211S t .0935 WEI LIVER (LI) S2.4930 2.1339 t .9431 WEI LF OVARY (OVO 1 .2040 .0083 % .0037 WEI RT OVARY (OV1) .1400 .0057 % .0025 WEI PANCREAS IPA) 4.1150 .1673 % .0739 WEI LP THYROID/PAI@A (TrO) .2030 .0093 t .0036 WEI RT THYROID/PARA (TTI) .1190 .0049 % .0021 WEI ------------------------------------------------------------------------------------------------------------ NECROPSY ---------------------------------------------- 0 B S B R V A T 10 N S @ HISTOPATHOLOGY 7 ----------------- --------------------------------------------- LIVER ILI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MININAL, HU -DEGENERATION/NECROSIS, HEPATOCELLULAR,-MIN THYMUS (TH) i -CYST,-PRESENT -ATROPHY.-MINIKKL SPINAL CORD (SC) : -PIGMENT, NEURONAL,-NRNIKAL GENERAL COMMENT (r.C) -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS APPENDIX 5 Individual Anatomic Pathology Data Terminal sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SnT (PFOS;T-629S) IN CYNOMOLOUS MONKEYS ----------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105545 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI DATE OF DEATH: 02/2S/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 DATE AND TIME OF NECROPSY: 02/2S/99 7:31 PROSECTOR: KEVIN BILLINGS TERMINAL BODY WEIGHT: 24 RECORDER: MICHELE ZIIC POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ----------------------------------------------------------------------------------------------------------------- 0 B S R R V A T 1 0 N S (CONTINUED) NECROPSY HISTOPATHOLOGY --------------------------------------------------------------- ---------------------------------------------- CENERA,L INFORXATION >NOTE: >GALLBLADDER (XX) : WEIGHT is 0.7210 GRAMS BILE VOLUME IS 1.4000 ML - -- - - - - ---- - - -- -- - - - - -- - - - - - - - - -- - - - - - THE FOLLOWING ORGANS WERE UNREKARKABLE AT NECROPSY: BONE, FEMUR IFE), MARROW, FEMUR (FM), NARROW, STERNUM (SE), BONE, STM*M (SB), EYE (]gY), MAIN (BRI, KID LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, NESENTERIC (KS), TRACH ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (KA). AORTA IAO), PITUITARY (]Pl), SALIV GL, HANDIB (SO), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, CL (ST), DUODENUM IDU), PANCREAS (PA), JFZUNUM (JE), ILEUM (IL), CBCUM (Cl3), COLON (CO), RECTUM SKIN (SK), HAMKARY, FEMALE (KF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGM (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHROBRON (TB), LN, ANT NES/PANC ----------------------------------------------------------------------------------------------------------------- Apommix 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLCUS MONKEYS --------------------------------------------L--------------------------------------------------------------------- ANIMAL NUMBER. 105548 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIF STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 286 DATE OF DEATH: 02/25/99 DATE AND TIME OF NECROPSY: 02/25/99 11:00 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ------------------------------------------------------------------------------------------------------------------ ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0R ORGAN NAME (GRAMS) TO BODY WEIGHT WEIGHT RATIO ST -------- -------- ---------------------LEFT ADRENAL IADO) -------- .3880 .2850 .0135 .0099 .0063 WEIG .0046 WEIG RIGHT ADRENXL IAI)L) BRAIN (BR) 61.9790 2.1633 1.0000 WEIG LF KIDNEY (KDO) 6.0250 6.0670 .2103 .2119 2.0163 .0972 WEIG .0979 WEIG .9320 WRIG RT KIDNEY (RDl) LIVER (LI) 57.7670 .2400 .0084 .0039 WEIG LF OVARY (OVO 1 RT OVARY (OV11 .1510 5.0690 .0053 % .1769 % .0057 % .0024 WEIG .0918 WEIG .0026 WEIG PANCREAS (PA) LP THYROID/PARh RT THYROID/PARA (TTO) (7rl) .1640 .1640 .0057 % .0026 WEIG -------------------------------------------------------------------------------------------------------------- 0B 9ERVAT 10N S NECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- LUNG (LU) -ADHESION(S); AE)HERED TO PLEURA, DIAPHRAGM, PERICARDIUM, AND LUNG (LU) >NOT REQUIRED TO BE EXAMINED FOR ANIMAL EACH OTHER: MULTIPLE GRAY, FIBROUS ADHESIONS; COLLECTED INTACT LIV_ER (LI) INFILTRATE, LYMPHOHISTIOCYTIC,-MODERATE, FC THYMUS (TH) : -ATROPHY,-NODMMTELY SEVERE SPINAL CORD (SC) : -PIGMENT, MVIRONAL,@-SLIGHT CECUM ICE) -RED FOCUS (I)/AR.EA(S); DIFFUSE: MULTIPLE DARK RED FOCI, UP TO 0.5 CH IN DIAM=R, COLLECTED ON ROUTINE SECTION CECUM (CE) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANS SULPONIC ACID POTASSIUM SALT IPFOS;T-6295) IN CYNOMOLCUS MONKEYS ------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: 105548 DATE OF DEATH: 02/25/99 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIF STUDY DAY OF DEATH- 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 286 DATE AND TIME OF NECROPSY: 02/25/99 11:00 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NO'3r AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ------------------------------------------------------------------------------------------------------------------ 0 B S E R V A T 1 0 N S (CONTINUED) NECROPSY HISTOPATHOLOGY ----------------------------------------------------------------------------------------------------------- GENERAL COMMENT (GC) : -BONE NARROW SHEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX I >NOTE: >GALLBLADDER WEICHT IS 0.7810 GRAMS BILE VOLUME IS 2.6000 ML -- - - - - - --- -- - - - -- - - -- - - - - - - -- - - - - - - - - - THE FOLLOWING OttGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), NARROW, FEMUR (PH), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KI HEART (HT), LIVER (LI), GALLBLADDER ICB), SPLEEN (SP), THYMUS (TH), LN, NESENTMIC (US), TRACHEA ITR). ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA IAO), PITUITARY (PI), SALIV OL, MANDIB (SG), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILMM,IXL), COLON (CO), RECTU14 (RE), SKIN MAMMARY, PEKALE (MF), URINARY BLADDER IUD). UTERUS (Lrr),OVARY (ov), VAGINA (VA), CERVIX (CV), ADIPOSE TI LN, TRACHBORIKON (TB), LN, ANT 14ES/PANC (AP) ----------------------------------------------------------------------------------------------------------------- APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS --------- ---------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105534 SEX: FEMALE STUDY DAY OF DEATH: DOSE GROUPT 4 185 STUDY WEEK SACRIFICE STATUS: OF DEATH: 27 SCHEDULED, TERMINAL SACRIF TERMINAL BODY WEIGHTT 250 DATE OF DEATH: 02/26/99 DATE AND TIME OF NECROPSY: 02/26/99 8:14 PROSECTORT STEVE VAN ADESTINE PATHOLOGIST: ROBERT LEEDLE RECORDER: JOHN S. HALF WEIGHER- JOHN S. HAL P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T--A-VA-I-L-A-BL-E--------------------------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0R S_T A ORGAN NAME (GRAMS) TO BODY WEIGHT (t) -------- WEIGHT RATIO ----- --- - ---------------------- -------- .0132 t .0061 WHIGII LEFT ADRENAL (ADO) .3290 .2270 .0091 % .0042 WEIG RIGHT ADRENAL BRAIN (ER) (ADl) 54.3510 4.8280 2.1740 t .1931 % 1.0000 .0888 .0918 WEIG WEI WEIG LF KIDNEY RT KIDNEY (KDO) (KD1) 4.9920 .1997 t 3.0220 % 1.3900 WHIG LIVER (LI) 75.5500 .0064 % .0029 WEIG LF OVARY (OVO) .1600 .1480 .0059 % .0027 WHIGI RT OVARY PANCREAS (OV1) (PA) 4.4740 .1790 % .0823 .0025 WEIG WHIG LP THYROID/PARh RT THYROID/PARA (TTO) (TTI) .1370 .1210 .0055 % .0048 t .0022 WEI WEIG GALLBLADDER (GS) .5260 BILE(VOLUME) (BI) 2.0000 aL ---------------------------------------------- -------------------------- 0B SBR VAT 10N S HISTOPATHOLOGY NECROPSY --------------------------------------------- ----------------------------------------------------------- --- BOW, FM4= (FE) i -GROWTH PLATE OPEN.-MODERATE KIDNEY (KD) : -MINERALIZATION, MEDULLA,-MINIMAL LUNG (LU) -DARK FOCUS (1) /AREA (S) ; PINPOINT FCCI -LIGHT FOCUS (I)/AREA (S) MULTIPLE TAN AREAS, UP ALL LOBES: MULTIPLE DARK BROWN RIGHT AND LEFT CAUDAL To 0.2 X 0.1 CH LOBES: LUNG (LU) : -HYPERPLASIA, MINIMAL -INFILTRATE, LYMPHOCYTIC, PERIBRONCHIOLAR/ MACROPHAGE, ALVBDLAR,-NINIMAL LIVER (LI) -INFILTRATE, LYMPHOHISTIOCYTIC.-MINIKhL, MTJL -HYPERTROPHY, HEPATOCELLULAR.-BLIGHT, DIFFUS 757 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS WoNyi3ys ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105534 DATE OF DEATH: 02/26/99 DATE AND TIME OF NECROPSY% SEX: FEMALE STUDY DAY OF 02/26/99 8tl4 DOSE GROUP: 4 SACRIFICE DEATH: 185 STUDY WEEK OF DEATH: PROSECTOR: STEVE VAN ADESTINE PATHOLOGIST: ROBERT LEEDLE STATUS: 27 SCHEDULED, TERMINAL SACRI TERMINAL BODY WEIGHTI 25 RECORDER: JOHN S. WEIGHER: JOHN S. HALFI P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T--A-VA-I-L-A-BL-E-------------------------------------------------------------------------- -------- 0 B S E R V A T 1 0 N S (CONTINUED) HISTOPATHOLOC;Y NECROPSY -- ----------------------------------------------------------- ------ --------------------------------------- LIVER (LI) i -VACUOLATION, HEPATOCELLULAR,-SLIGHT. DIFFUS ADRENAL, CORTEX (AC) -DIFFUSELY DARK; BILATERAL: BROWN CECUM (CE) -DARK FOCUS (I) /AREA (S); SEROSAL SURFACE AND LUMEN, DIFFUSET MULTIPLE DARK BROWN, SLIGHTLY RAISED AREAS, UP TO 0.5 X 0.2 THYMUS (TH) t -ATROPHY,-MODERATE TRACHEA (TR) : -INFILTRATE. LYMPHOHISTIOCYTIC.-SLIGHT ADRENAL, CORTEX (AC) >UNREMARKABLE DUODENUM (DU) -INFILTRATE, MACROPHAGE, PIGMENTED,-MODERAT JEJUNUM (JR) i -INFILTRATE, MACROPHAGE, PIGMENTED.-SLIGHT ILEUM (IL) s -INFILTRATE, MACROPHAGE, PIGKENTED.-SLIGHT CECUM (CE) : -PARASITISM,-PRESENT CM; COLLECTED ON ROUTINE SECTION COLON (CO) : -DARK FOCUS (1) /ARF-A(S); SEROSAL SURFACE AND LUMEN, DIFFUSE: MULTIPLE DARK BROWN, SLIGHTLY RAISED FOCI, UP To 0.3 CH IN COLA)N (CO) -PARASITISM, INTRAMSCULAR.-PRESENT DIAMETER; COLLECTED ON ROUTINE SECTION URINARY BLADDER (UB) t -INFILTRATE, LYMPHOHISTIOCYTIC,-MININAL ADIPOSE TISSUE (AT) -RAISED FOCUS (I) /AREA(S) ; MESENTERY, DIFFUSE: MULTIPLE TAN OVARY (OV) : -MINERALIZATION,-MINIMAL ADIPOSE TISSUE (AT) : -LYMPHOID TISSUE.-PRESENT FOCI, UP TO 0.3 C14 IN DIAMETER (CAP 29) 758 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS_NONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105534 SEX: FEMALE STUDY DAY OF DEATH: DOSE GROUP: 4 185 STUDY WEEK SACRIFICE STATUST OF DEATH: 27 SCHEDULED, TERMINAL SACRIF TERMINAL BODY WRIGHT: 250 RECORDER: JOHN S. HA DATE OF DEATH: 02/26/99 PROSECTOR: STEVE VAN ADESTINE DATE AND TIME OF NECROPSY: 02/26/99 8:14 PATHOLOGIST: ROBERT LEEDLB WEIGHER: JOHN S. HALF( P-O-S-T--F-I-X---WE-I-G-H-ER-:---N-O-T--A-V-A-IL-A-B-LE------------------------------------------------------------------------------------ 0 B S B R V A T 1 0 N S (CONTINUED) HISTOPATHOLOGY NECROPSY --------------------------------------------- ----------------------------------------------------------- - GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE). MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (BY). BRAIN (BR), KI HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN. NESEMERIC (MS), TRACHEA (TR). ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (NA), AORTA (AO), PITUITARY (pi), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SH), SPINAL CORD (SC). NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA). JEJUNUM (JE). ILEUM (IL), RECTUM (RE). SKIN (SK). MAMMARY, FEMALE (MF). URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), LN. TRACHBODROM (TB), IN. ANT HE THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: . MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE. STERNUM (SB), EYE (BY), BRAIN (SR), HEART (HT), (;ALLBLADE SPLEEN (SP), LN, MESENTERIC (MS). ESOPHAGUS (ES), THYROID (7'Y), PARHTHYROID (PT) ADRENAL, MEDULLA (MA). AORTA (AO), PITUITARY (PI), SALIV GL. MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATI STOMACH, GL (ST), PANCREAS (PA), RECTUM (RE). SKIN (SK), MAMMARY, FEMALE (MF), UTERUS (UT), VAGINA (VA). --------C-E-RV-I-X---(-CV-)----------------------------------------- --------------------------------------------------- 759 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105536 SEX: FEMALE STUDY DAY OF DEATH: DOSE GROUP: 4 SACRIFICE STATUS: 164 STUDY WEEK OF DEATH: 27 SCHEDULED, TERMINAL SACRIE TERMINAL BODY WEIGHT: 318 RECORDER: TODD ACKER DATE OF DEATH: 02/25/99 PROSECTOR: STEVE VAN ADESTINE DATE AND TIME OF NECROPSY: 02/25199 9:56 PATHOLOGIST: ROBERT LEEDLE WEIGHERT TODD ACKER P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T--A-V-A-I-LA-B-L-E ---------------------------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0R ST ORGAN NAME (GRAMS) To BODY WEIGHT (%) WEIGHT RATIO -------- ---- ---------------------- -------- -------.0103 % .0056 WRIG LEFT ADRENAL .(ADO) .3290 .2360 .0074 % .0040 WEIG RIGHT ADRENAL BRAIN (BR) (ADl) 58.3990 1.8336 t 1.0000 lL97 WHIG WEIG LF KIDNEY (KDO) 6.9900 .2195 % .2327 t .1269 WHIG RT KIDNEY (KD1) 7.4110 93.8600 2.9469 % 1.6072 WEIG LIVER (LI) LF OVARY (OVO) .1010 .1360 .0032 % .0043 % .0017 .0023 WEIG WRIG RT OVARY (OV1) 4.7900 .1504 % .0820 WEIG PANCREAS (PA) LF THYROID/PARA (TTO) .1910 .0060 % .0033 .0041 WEIG WEI RT THYROID/PARA (TTI) .2400 .0075 % WEIG GALLBLADDER (GB) .6650 -------B-I-L-E(-V-O-L-U-M-E-)----(-BI-)-----------------2-.6-0-0-0--m-L------------------------------------------------------------- 0 8S BRVA T10 N S HISTOPATHOLOGY NECROPSY -------------------------------------------- ---------------------------------------------------------------- NARROW, FEMUR (FI4) . >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) : -INFILTRATE, MACROPRAGES, PIGMENTED, PERIVA LUNG (LU) -DARK FOCUS (1) /AREA(S); ALL LOSES, DIFFUSE: MULTIPLE LUNG (LU) t >UNREMARKABLE PINPOINT BLACK FOCI LIVER (LI) ; -MOTTLED; ALL LOBES: BROWN AND TAN LIVER (LI) -HYPERTROPHY, -VACUOLATION. HEPATOCELLULAR, HEPATOCELLULAR, CENTRILOBULAR CENTRILOBULAR SEVERE 760 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PPOS:T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ------------------------------------------------------------------------------------------------------------ SACRIFICE STATUS: SCHEDULED. TERMINAL SACRIE ANIMAL NUMBER: 105536 SEX: FE14ALE DOSE GROUP: 4 STUDY DAY OF DEATH* 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 318 RECORDER: TODD ACKER DATE OF DEATH: 02/25/99 DATE AND TIME OF NECROPSY: 02/25/99 9:56 PROSECTOR: STEVE VAN ADESTINE WEIGHER: TODD ACKER PATHOLOGISTs ROBERT LEEDLE P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T --A-V-A-I-LA-B-L-E----------------------------------------------------------------------------------- 0 B S 8 R V A T 1 0 N S (CONTINUED) HISTOPATHOLOGY NECROPSY ------ -------------------------------------- ------------------------------------------------------------ GALLBLADDER (GB) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIHAL THYMUS (TH) * -CYST,-PRESENT -ATROPHY.-MODERATELY SEVERE TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC.-SLIGHT ADRENAL, CORTEX (AC) -DIFFUSELY DARK; BILATERAL: BROWN THYROID , (TY) I -CYST , ULTIMOBRANCHIAL.-PRESEW ADRENAL CORTEX (AC) : -HYPERTROPHY, CORTICAL CELL.-MINIMAL -PIGMENT,-SLIGHT SALIV GL, MANDID (SG) -INFILTRATE. LY14PHOHISTIOCYTIC,-HINIMAL SPINAL CORD (SC) : -PIGMENT, NEURONAL.-HODERATE DUODENUM (DU) t -INFILTRATE, MACROPHAGE. PIGMENTED,-SLIGHT JEJUNUM (JE) : -INFILTRATE, MACROPRAGE, PIGMMffED.-SLIGHT ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGNE2ffED,-SLIGHT CECUM (CE) i -INFILTRATE, 14ACROPHAGE, UTERUS (UT) : PIGMENTED.-SLIGHT -Al4YLOID,-MODERATE OVARY (OV) : _AMYLOID,-MODERATE -ONE EXAMINED.-PRESENT 761 APPENDIX 5 individual Anatomic PatholOgY Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS:T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------- --------------------------------------------------- SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIF ANIMAL NUMBER: 105536 SEX: FEMALE DOSE GROUP: 4 STUDY WEEK OF DRATHT 27 TERMINAL BODY WEIGHT: 318 DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 PROSECTOR: STEVE VAN ADESTINE RECORDERT TODD ACKER DATE AND TIME OF NECROPSY: 02/25/99 9:56 PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER P-O-S-T---FI-X---W-E-IG-H-E-R-: ---N-OT---A-VA-I-L-A-BL-E---------------------------------------------------------------------------------- - 0 B S E R V A T 1 0 N S (CONTINUED) HISTOPATHOLOC;Y NECROPSY ---------------------------------------------- ---------------------------------------------------------------- GENERAL -BONE -EYES COMMENT (GC) NARROW SMEAR TAKEN - DAVIDSONS ------ ---------- - - -THE FO-LLOW-ING- -ORGA-NS -WER-E -UNRE-MARK-ABLE- -AT -NEC-ROPS-Y: - - BONE, FEMUR (IFE), NARROW, FEMUR (FM), NARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (BY), BRAIN (BR). KI HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, NESENTERIC (MS). TRACHEA (TR), ESOPHAGUS (ES) THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO) PITUITARY (PI), SALIV GL, MANDIB (SG). MUSCLE, SKELETAL (SM), SPINAL CORD (SC). NERVE, SCIATIC (SN), K46;m@H, GL (ST), DUODENUM (OU), PANCREAS ( JEJUNUM (JE), ILEUM (IL). CECUM (CE), COLON (CO), RECTU14 (RE). SKIN (SK), MAMMARY, FEMALE (MF), URINARY B UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN. TRACHBOBRON (TB), LU. ANT NES THE FBOOLNLEO,WINGFEMURTIS(SUFEES), WNEARREROWU,NREMSATREKRANBULME (SAET), 14BIOCNREO,SCOSPTICERNUEMXAMI(NSABT)I.ON:EYE (EY), KIDNEY (KD). HEART (HT), SPLEEN (SP LN, HESENTERIC (MS), ESOPHAGUS (Eg), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), PANCREAS (PA), COLON (CO). RECTUM (RE), SKI MAMMARY, FEMALE (MF), URINARY BLADDER (UB), VAGINA (VA), CERVIX (CV) --------------------------------------------------------------------------------------------------------------- 762 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNONOLGUS NONKEYS --------------------------------------------------------------------------------------------------- ANIMAL NU14BER: 105540 SF.X: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIF TER14INAL BODY WEIGHT: 270 DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH; 185 STUDY WEEK OF DEATH: 27 RECORDER- JOHN S. HAL DATE AND TIME OF NECROPSY: 02/26/99 10:20 PROSECTOR: STEVE VAN ADESTINE WEIGHER: JOHN S. HAL POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE -------- ------------- --------------------- ----------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE 7 ORGAN TO BRAIN 0R ORGAN NAME ---------------------- (GRAMS) -------- TO BODY WEIGHT (t) -------- WEIGHT RATIO -------- .0061 ST) ----- WEIG LEFT ADRENAL (ADO) .3440 .0127 t .0094 t .0045 WEIG RIGHT ADRENAL BRAIN (BR) (ADl) .2550 56.3190 2.0859 t .1929 t 1.0000 .0925 WEIG WEIG LF KIDNEY RT KIDNEY (KDO) (KD1) 5.2090 4.8440 .1794 t 2.3361 t .0860 1.1200 WEIG WHIG LIVER (LI) 63.0760 .0052 t .0025 WEIG LF OVARY (OVO) .1400 .1410 .0052 t .0025 WEI RT OVARY (OV1) 4.4510 .1649 t .0790 WEIG PANCREAS (PA) LF THYROID/PARA (TTO) .2480 .0092 % .0044 .0045 WEIG WEIG RT THYROID/PARA (TTi) .2540 .0094 t WEIO GALLBLADDER (GB) .5650 -------B-I-L-E(-V-O-L-U-M-E-)----(B-I-)-----------------1.-6-0-0-0--M-L --------------------------------------------------------------- 0 B SBRV AT 10N S HISTOPATHOLOGY NECROPSY --------------------------------------------- ---------------------------------------------------------------- NARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (OR) : -INFILTRATE. MACROPHAGES, PIGMENTED, PERIVA@C LUNG (LU) -RED FOCUS (1) /AREA (S) ; RIGHT CAUDAL AND APICAL WBES: LUNG (LU) -HEMORRHAGE,-MODERATE MULTIPLE DARK RED INDISTINCT AREAS LIVER (LI) -INFILTRATE, LYMPHOHISTIOCYTIC,-MININAL, mu -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULRR. THYMUS (TH) : -CYST.-PRESENT 763 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULPONIT ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS -------- ------------------------------------------------------------------------------------------------------ SACRIFICE STATUS: SCHEDULED, TERMINAL SACRI ANIMAL NUMBER: 105540 SEX: FEMALE DOSE GROUP: 4 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 27 DATE OF DEATH- 02/26/99 STUDY DAY OF DEATHT 185 PROSECTOR: STEVE VAN ADESTINE RECORDERT JOHN S. HAL DATE AND TIME OF NECROPSY: 02/26/99 10:20 PATHOLOGIST: ROBERT LEEDLE WEIGHER- JOHN S. HA P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T --A-V-AI-L-A-B-LE---------------------------------------------------------------------------------- 0 B S E R V A T 1 0 N S (CONTINUED) HISTOPATHOLOGY NECROPSY ---------------------------------------------------------- ---- ----- ---------------------------------------THYMUS (TH) : -ATROPHY.-SLIGHT TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL THYROID (TY) : -CYST, ULTIMOBRANCHIAL.-PRESENT AORTA (AO) : -PROLIFERATION, INTIMAL.-HODERATE MUSCLE, SKELETAL (SH) : -INFILTRATE. LYMPHOHISTIOCYTIC,-MININAL DUODENUM (DU) : -INFILTRATE, MACROPHAGE. PIGMENTED.-SLIGHT SKIN (SX) -ALOPECIA-FOCAL; RIGHT DORSAL THORACIC REGION: 0.3 X 2.5 CH SKIN (SK) : -HAIR FOLLICLES, DECREASED,-140DERATE (CAP 29) GENERAL COMMENT (GC) -BONE MARROW SHEAR TAKEN -EYES - DAVIDSONS - - - - - - - - -- - - - - - - - - - - - -- - - - - - - - - - - - - - - 764 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------- ----------------------------------------------------------------- SACRIFICE STATUS: SCHEDULED, TERMINAL SACRII ANIMAL NUMBER: 105540 DATE OF DEATH: 02/26/99 SEX: FEMALE DOSE GROUP: 4 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 27 RECORDER: JOHN S. HA PROSECTOR.- STEVE VAN ADESTINE DATE AND TIME OF NECROPSY: 02/26/99 10:20 PATHOLOGIST: ROBERT LEEDLE WEIGHERT JOHN S. HA P-O-S-T--F-I-X--W-E-I-GH-E-R-: ---N-OT-- A-V-A-IL-A-B-LE-------------------------------- ------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT DONE, FEMUR (FE), MARROW. FEMUR (FM), NECROPSY: HARROW, STERNUM (SE), BONE, S.TERNUM (SB). EYE (EY). BRAIN (BR). KI LN, NESENTERIC (MS). TRACHEA (TR), HEART (HT), LIVER (LI). GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH) ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA). AORTA (AO), PITUITARY (PI). SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC). NERVE, SCIATIC (SH), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JR), ILEUM (IL). CECUM (CE), COLON (CO), RECTUM MAMMARY, FEMALE (MF), URINARY BLADDER (US), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TI LN, TRACHEOBRON (TB), LM, ANT MES/PANC (AP) FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: THE BONE, FEMUR (FE). MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), KIDNEY (KD), HEART (HT), GALLBLADDV SPLEEN (SP), LN, NESENTER]IC (MS), ESOPHAGUS (ES), PARATHYROID (PT), ADRENAL. . CORTEX (AC), ADRENAL, NEDUL STOMACH, GL (ST), PANCREAS PITUITARY (PI), SALIV GL. MANDIB (SG), SPINAL CORD (SC), NERVE, SCIATIC (SN) JF.JUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE). MAMMARY, FEMALE (MF), URINARY BLADDER (US) UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV) ------------------------------------------------------------------------------------ ------------------------- 765 APPENDIX 5 individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS:T-6295) IN CYNOMOLGUS MONKEYS --------------------------------- ---------------------------------------------------------------------------- ANIMAL NUMBER: 105551 SEX- FEMALE STUDY DAY OF DEATH: DOSE GROUP: 4 SACRIFICE STATUS: 185 STUDY WEEK OF DEATH: 27 SCHEDULED, TERMINAL SACRI TERMINAL BODY WEIGHT: 22 RECORDER: MICHELE ZIN DATE OF DEATH: 02/26/99 PROSECTOR: KEVIN BILLINGS DATE AND TIME OF NECROPSY: 02/26/99' 7:43 PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIKA P-O-S-T--F-I-X---WE-I-G-HE-R-:---N-O-T--A-V-AI-L-A-BL-E----------------------------------------------------------------------------------- ABSOLUTE ORGAN WEIGHT ORGAN WEIGHT RELATIVE ORGAN TO BRAIN 0R ORGAN NAME (GRAMS) TO BODY WEIGHT (t) -------- WEIGHT RATIO -------- ST ---- ---------------------LEFT ADRENAL (ADO) -------- .3850 .2960 .0173 % .0133 t .0065 .0050 WEIG WEIG RIGHT ADRENAL (ADI) 59.3140 2.6598 t 1.0000 WEIG BRAIN (BR) 6.0280 .2703 t .1016 WEIG LF KIDNEY RT KIDNEY (KDO) (KDI) 5.9040 68.7130 .26&8 t 3.0813 t .0995 1.1585 WEIG WHIG LIVER (LI) .2350 .0105 t .0040 WEIG LF OVARY (OVO) .1740 .0078 t .0029 WEIG RT OVARY PANCREAS (OVI) (PA) 3.7750 .1730 .1693 % .0078 t .0073 t .0636 .0029 .0027 'WEIG WEI WEI LF THYROID/PARJk RT THYROID/PARA (TTO) (TTI) .1630 WEI( GALLBLADDER (r.B) .6040 -------B-I-L-E-(-VO-L-U-M-E-)----(-B-I)--------- --------1-.8-0-0-0--M-L------------------------ ------------------------------------ 0 B S E RV NECROPSY ---------------------------------------------------------- ---- AT 10N S HISTOPATHOLOGY -------------------------------------------- NARROW, FBMJR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) : -INFLAMMATION, LYMPHOHISTIOCYTIC,-MINIMAL KIDNEY (KD) : -MINERALIZATION, MEDULLA,-MINIKAL LUNG (LU) -RED FOCUS (I) /AREA(S); ALL LOBES: 14ULTIPLE DARK PINPOINT AND UP TO 1 Mt4 IN DIAMETER RED FOCI, LUNG (LU) 3 >UNREMARXABLE LIVER (LI) _INFILTRHTE, LYMPHOHISTIOCYTIC,-MININAL, HU -HYPERTROPHY, HEPATOCELLUL)KR. CENTRItoOBUtJkR 766 APPENDIX 5 individual Anatomic Patholo" Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PEItFtUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------- ANIMAL NUMBER: 105551 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUST SCHEDULED, TERMINAL SACRIF TERMINAL BODY WHIGHTT 223 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 RECORDER: MICHELE ZINA DATE OF DEATH, 02/26/99 DATE AND TIME OF NECROPSY: 02/26/99 7:43 PROSECTOR: KEVIN BILLINGS PATHOtA)GISTs ROBERT LEEDLE WEIGHER: MICHELE ZIMA P-O-S-T--F-I-X--W-E-IG-H-E-R:---N-O-T -A-V-A-I-LA-B-L-E --------------------------------------------------------------------------------------- 0 B S E R V A T 1 0 N S (CONTINUED) HISTOPATHOT.OGY NECROPSY ---------------------------------------------- ---------------------------------------------------------------- GALLBLADDER (OB) : -INFILTRATE, LYMPHOHISTIOCYTIC.-MINIKAL TRACHEA (TR) i -INFILTRATE. LYMPHOHISTIOCYTIC,-MINIHAL THYROID (TY) : -INFILTRATE, LYMPHOHISTIOCYTIC.-MINIMAL SALIV GL, MANDIB (SO) : -INFILTRATE, LYMPHOHISTIOCYTIC.-MININAL MUSCLE, SKELETAL (SH) : -PARASITES, CYST,-PRESENT SPINAL CORD (SC) s . -PIGMENT. NEURONAL 140DERATE JEJUNUM (JR) : -INFILTRATE, MACROPHAGE. PIGMENTED,-SLIGHT SKIN (SK) -ALOPECIA-DIFFUSE; ALL FOUR LIMBS- RAIRCOAT THIN; COLLECTED SKIN (SK) : -HAIR FOLLICLES, DECREASED,-SLIGHT GENERAL COMMENT (GC) : -BONE NARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFOP14ATION (XX) - >N-(Yr-E:>-ANIK-hL -APP-EAR-S T-O B-E I-N E-STR-OUS- - - - - - - - - - - - - - - --------- 767 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ---------------------------------------------------------------------------------------------------------------- SACRIFICE STATUS: SCHEDULED, TERMINAL SACRII ANIMAL NUMBER: 105551 SEX: FEMALE DOSE GROUP: 4 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 22, DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIM) DATE AND TIME OF NECROPSY: 02/26/99 7:43 PATHOLOGIST: ROBERT LEEDLE WEIGHERT MICHELE Z114A P-O-S-T--F-I-X---WE-I-G-HE-R-T---N-O-T--A-VA-I-L-A-BL-E-------------------------------- ---------------------------------------------------- THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE). MARROW, FE14UR (FM), NARROW, STERNUM (SE), BONE, STERNUM (SE), EYE (EY). BRAIN (BR). KI TRACHEA (TR). HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, HESENTERIC (MS) * ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM MAMMARY, FEMALE (MF) URINARY BLADDER (UB), UTERUS (UT) I OVARY (OV). VAGINA (VA), CERVIX (CV), ADIPOSE TI LN, TRACHEOBRON (TB): LN, ANT MES/PANC (AP) FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATIONs THE BONE, FE14UR (FE), NARROW, STERNUM (Sg), BONE, STERNUM (SB), EYE (BY). HEART (HT), SPLEEN (SP), THYMUS (TH LN, NESENTERIC (MS), ESOPHAGUS (ES). PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL. MEDULLA . (KA). AORTA PITUITARY (PI), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), ILEUM (IL)V,AGICNEACUM(VA()C COLON (CO), RECTUM (RE), MAMMARY, FEMALE (KF), URINARY BLADDER (UB), UTERUS (UT). OVARY (OV) --------C-ER-V-I-X---(-C-V)--------------------------------------------------------------------------------------------- 768 APPENDIX 5 individual Anatomic Pathology Data Recovery sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS:T-6295) IN CYNOMOLGUS MONKEYS --------------------------------------------------------------------------------------------------- SACRIFICE STATUS: ANIMAL 14UMBER: IOSSII SEX: IIALE DOSE GROUP: 4 STUDY WEEK OF DEATH: 79 DATE OF DEATH: 02/25/00 STUDY DAY OF DEATH: 549 PROSECTOR: KEVIN BILLI14GS DATE AND TIME OF NECROPSY. 02/25/00 7:S6 PATHOLOGIST: AS ASSIGNED POST-FIX WEIGHER: IIOT AVAILABLE -- - -- - -- - -- -- - - - -- - -- - - - -- -- -- -- -- - -- -- - -- -- - -- - -- - -- - -- -- - - -- - -- -- - -- -- - -- - - -- -- - -- - - - SCHEDULED, FIRST POST-REC TERMINAL BODY WEICHT: 424 P.ECORDEP.: MICHELE ZIMA WEIGHEP.: I-IICHELE ZIMA 7 - -- - - -- - --- -- - -- - -- - -- - *** ORGAN WEIGHTS WERE NOT RECORDED *-* ---------------------------------------------------------------------------------------------------------------- NECROPSY ----------------------------------------------------------- --- HISTOPATHOLOGY ------ --------------------------------------- LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT GENERAL COMMENT -NO MACROSCOPIC IGC) LESIONS - - - -- - - - - - - - - - - - -- - -THE FO-LLOW-ING - O-RGAN-S -WER-E -UNRE-MARK-ABLE- -AT LIVER (LI). ]BONE, FEMUR (FE), KARROW, -NEC-ROPS-Y: FEMUR (FM), NARROW, STERNUM (SE), BONE, STERNUM (SB). EYE (EY). BRA KIDNEY (KD), LUNG (LU), HEART (HT),' GALLBLADDER IGB). SPLEEN (SPI, THYMUS (TH), LN, HESEPRERIC (MS). TRAC ESOPHAGUS (ES). THYROID (TY), PARATHYROID (PT). ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MAI, AORTA (AO), PITUITARY (PI), SALIV OL. MANDIB (SC), MUSCLE, SKELETAL (SH), SPINAL CORD (SC). NERVE. SCIATIC (SN), STOMACH, GL (ST), DUODENUM (Du), PANCREAS (PA). JEJUNUM (JE), ILEUM (IL), CECUM (CE). COLON ICO). RECTUM SKIN (SK), MAMMARY, MALE IMM), URINARY BLADDER IUB), PROSTATE IFRI, SEMINAL VESICLES (SV), EPIDIDYKIDES TESTIS ITE), CAVITY, THORACIC (TA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: --------L-I-VE-R-.---BI-O-P-S-Y---(-LI-O-)------------------------------------------------------------------------------------ APPENDIX S Individual Anatomic Pathology Data Recovery Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTA24E SULPONIC ACID p(YrAssium SALT IPFOS;T-6295) IN CYNOMOLCUS MOIIKEYS ----------------------------------------------------------------------------------:-------------------------------- JUJINAL NUMBER: IOSS22 DATE OF DEATH- 02/25/0(P DATE AND TIME OF NECROPSY: SEX- 14ALE DOSE GROUP: 4 SACRIFICE STATUS- STUDY DAY OF DEATH: S49 STUDY WEEK OF DEATH: 79 02/25/00 11:3S PP.GSECTOR: KEVIII BILLINGS SCHEDULED, FIRST POST-REC TEPJ4IIIAL BODY WEIGHT: 435 RECORDER: MICHELE ZINA POST-FIX WEIGHER: ZIOT AVAILABLE PATHOLOGIST: AS ASSIGNED I-JEIGHER: MICHELE ZIW4 ------------------------------------------------------------------------------------------------------------------ ORCAN WEIGHTS WERE TIOT P.ECOPZED ------------------------------------------------------------------------------------------------------------- 0 BSE RVAT 10N S IJECROPSY HISTOPATliOLOGY -------------------------------------------------------------------------------------------------------------- LIVER, BIOPSY (LIO) : -PIGMENT, HEPATOCELLULAR,-SLIGHT LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-NODERATE -PIGMENT, HEPATOCELLULAR,-SLIGHT -HYPERPLASIA, BILE DUCT.-MODERATE -INFLAMMATION, EOSIIIOPHTLIC, PERI-BILE DUCT, LUNG (LU) -ADHESION(S); ALL EA313ESTO EACH OTHER, PLEURA, PERICARDIAL SAC AND CAUDAL LORIES TO DIAPHRAGM: MULTIPLE TAII FIBROUS LUNG (LU) ; >ZIOT REQUIRED TO BE EXAMINED FOR AIIIHAL ADHESIONS CAVITY, THORACIC (Th) -HODULE(S); WITHIN ADHESIONS: MULTIPLE TAN AND FIRM NODULES, UP To 0. 3 CH in DIAMETER - -- - - - - - --- - - - - -- - - - - - - - - - - - - - - -- - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY-. LIVER (LI), WHE, FEMUR (FE), MARROW, FEMUR (PH), MARROW, STERNUM (SE), DONE, STERNU14 (SBI, EYE (EY), BRK KIDNEY (KD). HEART (HT). GALLBLADDER (GB), SPLEEN ISP). THYMUS (TH), IN, MESENTERIC (MS), TRACHEA (TR) ESOPHAGUS (ES). THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC). ADRENAL, MEDULLA (MA), AORTA (IkO;, PITUITARY (Pli, SALrv GL, KANi)rs (sal, MUSCLE, SKELETAL (SH), SPINAL CORD (SC), NERVE, SCIATIC (ON), WMKKCH, CL (ST), DUODENUM (DUI, PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM SKIN (SKI, MA14MARY, 14ALE (KK), URINARY BLADDER (US), PROSTATE (PRI, SEMINAL VESICLES (SVI, EPIDIDYNIDES TESTIS (TE), GENERAL COMMENT (CC) ------------------------------------------------------------------------------------------------------------------ APPENDIX 5 individual Anatomic Pathology Data Recovery Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PF"LUOROOCTAIIE SULPONIC ACID POTASSIUM SALT IPFOS:T-6295) 114 CYTIONOLGUS 14ONKEYS ------------------------------------------------------------------------------------------------------------------ MIIMAL NUMBER: 105533 SEX: FEMALE DOSE GP.OUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-P.EC DATE OF DEATH: 02/2S/00 STUDY DAY OF DEATH.- 549 STUDY WEEK OF DEATH. 79 TERMINAL BODY WEIGHT: 253 DATE AND TINE OF NECP.OPSY: 02/25/00 8:58 PF.OSECTOR: KEVIN BILLINGS PZCORDER: MICHELE ZINA POST-FXX WEIGHER: NOT AVAILABLE PATHOLOGIST: AS ASSIGNED WEIGHER: MICHELE ZINA ------------------------------------------------------------------------------------------------------------------ *** ORGAN WEIGHTS WERE NOT RECORDED *** ------------------------------------------------------------------------------------------------------------------ 0 5 S E R V A T 1 0 ItS NECP.OPSY HTSTOPATHOLOGY --------------------------------------------------------------------------------------------------------------- LIVER ILI) : -ADMESIONIS); DIAPHRAGMATIC SURFACE OF RIGHT MEDIAIJ LOBE TO DIAPHRAGM: SIIIGLE TAN, FIBROUS LINEAR AREA. 2.0 CH III LEIIGTH LIVER (LI) : -FIBROSIS, CAPSULAR.-SLIGHT GALLBLADDER (GBI : GALLBLADDER (GB) - >140TE:>MO BILE AVAILABLE FOR SPECIAL PROCEDIJRE -NOT REQUIRED TO BE EXAMINED FOR ANIMAL - - - - - - - - - - - -- - - - - - -- -- - - - - - -- - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: DONE, FEMUR IFE), NARROW, FEMUR IFM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BRI. KID14 LUNG (LU), HEART (HT), GALLBLADDER IGB), SPLEEN ISP). THYMUS (TH). Lfl. MESEIITERIC (14S). TRACHEA (TRI, ESOPHAGUS (ES), THYROID ITY), PARATHYROID (PT). ADPMGAL, CORTEX (AC), ADPMIAL. MEDULLA (KAI, AORTA (AOI, PITUITARY IPI), SALIV GL, MANDIS (SGI, MUSCLE, SKELETAL (SM), SPINAL CORD (SCI, NERVE. SCIATIC (SN). STOMACH, GL IST), DUODENUM tDU), PANCREAS (PA), JEJUNUM (JEI. ILEUM (IL), CECUM (CE), COLOII (CO), RECTUM SKIN ISKI, MAMMARY, FEMALE (MFI, URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), GENERAL COMMENT (CC), CAVITY, THORACIC (Thl THE FOLLOWING TISSUES WERE UNREMARKABLE LIVER. BIOPSY (LIO) AT MICROSCOPIC EXAMINATION- ------------------------------------------------------------------------------------------------------------------ APPEMIX S individual Anatomic Pathology Data Recovery sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: IOSS42 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RE( DATE OF DEATH- 02/25/00 STUDY DAY OF DEATH: 549 STUDY WEEK OF DEATH: 79 TERMINAL BODY VMIGHT: 370 DATE AND TntE OF NECROPSY: 02/25/00 9:23 PROSECTOR: KEVIII BILLIIIGS RECORDER: 14ICHELE ZIN) POST-FIX WEIGHER: IJOT AVAILABLE PATHOLOGIST: AS ASSIGNED WEIGHER: MICHELE ZI@IA ----------------------------------------------------------------------------------------------------------------- ORGAII WEIGHTS WERE NOT RECORDED ----------------------------------------------------------------------------------------------------------------- 0 B S E R V A T 1 0 14S NECROPSY HISTOPATHOLOGY -------------------------------------------------------------------------------------------------------------- LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MltflKAL GENERAL COMMENT (GC) -NO MACROSCOPIC LESZONS - -- - - - - - - -- - - - - - -- - - -- -- - - - - - - - -- - -- - - THE FOLLOWING ORR-ANS WERE UIIREMARKABLE AT NECROPSY: LIVER (LI), DONE, FEMUR (FE), NARROW, FEMUR (FM), NARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY). BRA KIDIIEY (KD), LUNG (LU), HEART (HT), GALLBLADDER (GBI, SPLMM (SPI. THYMUS (TH), LN, MESMMRIC (NS), TRAC ESOPHAGUS (US), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC). ADRENAL. MEDULLA (MAI. AORTA (AO). PITUITARY IPT), SALIV GL, MANDID ISG). MUSCLE, SKELETAL (SM). SPINAL CORD (SC), NERVE, SCIATIC (Stil, STOMACH, GL (ST), DUODENUM COU), PANCREAS (PA). JEJTRIUM (JE). ILEUM (ILI, CE)CUM (CEI, COLOIJ (CO), RECTUM SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT). OVARY (OV), VAGINA (VA), CERVIX (CV), CAVITY, THORACIC (TA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXHNINATION: LIVER, BIOPSY (LIO) ----------------------------------------------------------------------------------------------------------------- APPENDIX 6 Covance 6329-223 3M T-6295.7 Summary and IndividuaBllood Hormone Determination Note: Thisappendixcontainsinformatiosnuppliedby Ani LyticsInc. 769 Appendix 6 Summary and Individual Blood Hormone Determination Day -50 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAM ACID POTASSIUM SALT (PFOS;T-6295) IN CYKMOLGUS SULPONIC MONKEYS ANIMAL NUMBER ------ CORTISOL #g/dL -------- TESTOSTERONE ng/mL ------------ Group: Male 1 Dose Level: 0 105508 105517 105519 105520 105526 105527 MEAN S.D. N 54.69 49.55 64.74 47.30 60.37 50.69 54.56 6.785 6 14.54 3.04 6.12 10.74 0.09 6.40 6.84 5.199 6 Group: Male 2 Dose Level: 0.03 105514 105515 105516 105521 71.04 39.63 58.36 58.05 1.19 9.81 0.34 14.26 MEAN S.D. N 56.52 13.374 4 6.40 6.767 4 Group. Male 3 Dose Level: 0.15 iossos 105510 105518 105523 105524 105528 48.00 38.05 50.92 56.98 62.46 63.18 3.04 0.41 3.77 4.38 1.02 0.97 MEAN S.D. 53.27 9.606 6 2.27 1.674 6 ESTRADIOL pg/mL --------- ESTRONE pg/mL ------- ESTRIOL pg/mL ------- Dosage Unitt mg/kg/day 29.48 51.76 31.21 30.92 31.69 43.40 20.01 54.86 17.51 39.76 27.63 24.47 0.00 0.00 0.00 0.00 0.00 0.00 36.41 9.077 6 30.71 14.158 6 0.00 0.000 6 Dosage Unit: mg/kg/day 38.90 27.91 32.30 59.78 51.37 17.75 29.41 62.35 0.00 0.00 0.00 0.00 39.72 14.114 4 40.22 20.296 4 0.00 0.000 4 Dosage Unit- mg/kg/day 43.24 23.74 53.56 43.26 30.26 26.50 30.43 26.96 28.80 39.3S 26.55 18.67 0.00 0.00 0.00 0.00 0.00 0.00 36.76 11.692 6 28.46 6.696 6 0.00 0.000 6 THYROID STIMULATING 103imL ------------------- TOTAL TRIXODOTHYROMI ng/dL -------------- 0.44 0.98 0.92 2.11 0.86 3.34 1.44 1.084 1.44 1.04 1.13 1.45 1.27 0.211 4 1.20 0.60 1.67 0.00 0.62 1.04 0.96 0.578 6 89.59 125.67 02.21 122.59 132.25 102.72 209.17 20.673 6 133.26 83.16 138.37 130.06 121.22 25.600 4 122.64 115.95 124.80 162.12 117.52 113.68 126.12 18.122 6 770 Appendix 6 Summary and Individual Blood Hormone Determination Day -50 26-WEEK CAPSULE TBXICITY STUDY WITH PERFLUOROOCTME SULFCNIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKSYS ANIMAL NUMBER ------ CORTISOL jig/dL -------- TESTOSTERONE ESTRADIOL ng/mL pg/mL ------------ --------- ESTROME pg/mL ------- ESTRIOL pg/oL ------- Group: Male 4 Dose Level: 0.75 105506 105507 105509 105511 105512 105522 46.92 41.20 65.60 48.27 49.15 44.81 3.31 21.45 2.21 18.86 0.29 12.56 MEAN S.D. N 49.33 8.464 6 9.76 9.117 6 Group: Female I Dose Level: 0 105529 105530 105531 rO553S 105544 105549 69.63 64.90 55.89 51.86 55.61 52.20 0.49 0.03 0.36 0.38 0.38 0.04 MEAN S.D. N 58.18 6.956 6 0.28 0.195 6 Group: Female 2 Dose Level: 0.03 105537 105541 105547 105550 73.24 62.66 71.82 46.90 0.19 0.66 0.16 0.29 MEAN S.D. 66.66 25.280 4 0.33 0.230 4 Dosage Unit: mg/kg/day 26.45 49.83 30.80 32.75 38.12 49.93 37.98 9.951 6 29.18 33.79 24.47 46.01 22.90 40.77 34.19 10.950 6 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 Dosage Unit: mg/kg/day 48.75 48.53 53.05 50.13 37.23 50.33 38.12 32.43 61.53 31.55 26.87 27.55 0.00 0.00 0.00 0.00 0.00 0.00 48.0 S.519 6 36.34 12.984 6 0.00 0.000 6 Dosage Unit; mg/kg/day . 91.05 60.36 55.87 50-49 129.22 42.73 39.96 46.09 o.oo 0.00 0.00 0.00 54.44 10.191 4 64.50 43.219 4 0.00 0.000 4 TOTAL THYROID STIMULATING TRIIODOTHYRCNI IM/mL ng/dL --------------------------------- 0.08 1.45 1.81 0.42 0.60 1.66 1.00 0.726 6 0.75 0.74 0.30 1.24 2.67 0.69 1.05 0.838 6 148.18 113.67 112.11 152.20 162.79 151.90 140.14 21.669 6 91.26 253.02 45.26 128.93 96.13 87.95 100.43 37.095 0.00 0.65 0.79 0.88 0.59 0.399 4 158.33 140.97 215.35 107.01 130.42 23.561 4 771 Appendix 6 Summary and Individual Blood Hormone Determination Day -50 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTMM ACID POTASSIUM SALT IPFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ANIMAL NUKBER ------ CORTISOL Ug/dL - -------- TESTOSTERONE ng/mL ------------ Group: Female 3 Dose Level: 0.15 105532 105538 105539 105545 105548 105552 MEAN S.D. N Group: 56.59 51.32 66.59 63.69 65.26 49.09 0.13 0.23 0.34 0.25 0.45 0.33 58.76 7.502 6 0.29 0.110 6 Female 4 Dose Level; 0.75 105533 105534 105536 105540 105542 105551 59.99 59.49 51.68 46.17 87.39 67.04 0.35 0.05 0.29 0.15 0.63 0.38 MEAN S.D. N 61.79 14-438 6 0.31 0.201 6 ESTRADIOL pg/mL --------- ESTRONE pg/mL ------- ESTRIOL pg/mL ------- Dosage Unit: mg/kg/day 51.67 52.69 129.12 176.45 63.53 23.32 35.53 35.81 82.62 132.50 47.80 15.96 0.00 0.00 0.00 0.00 0.00 0.00 82.00 57.794 6 58.37 42.494 6 0.00 0.000 6 Dosage Unit: mg/kg/day 96.99 42.90 47.76 54.58 39.07 86.86 64.39 34.98 46.31 89.39 31.01 107.99 0.00 0.00 0.00 0.00 0.00 0.00 61.36 24.447 6 62.31 30.672 6 0.00 0.000 6 THYROID STIMULATING /M/RL ------------------- TOTAL TRIZOVOTHYRONI ng/dL -------------- 4.46 0.00 1.48 0.67 0.00 1.52 1.36 1.663 6 2.10 0.98 0.17 1.51 0.32 0.21 0.88 0.795 6 64.50 137.04 117.92 135.57 104.23 71.94 105.20 31.182 6 101.63 97.38 124.27 126.16 109.29 95.16 108.98 13.460 6 772 Appendix 6 Summary and Individual Blood Hormone Determination Day -40 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CORTISOL TESTOSTERONE ESTRADIOL ESTRONE ug/dL ng/mL pg/ML pg/mL -------- ------------ --------- ------- ESTRIOL pg/mL ------- Group: Male I Dose Level: 0 Dosage Unit: mg/kg/day 105508 105517 105519 105520 105526 105527 57.43 43.65 71.52 52.42 84.79 79.36 3.30 2.35 0.37 11.10 0.21 5.72 23.93 42.46 32.19 46.29 26.36 33.96 11.61 29.34 19.63 3S.48 20.87 34.93 0.00 0.00 0.00 0.00 0.00 0.00 MEAN S.D. N Group: Male 64.86 16.197 6 3.84 4.098 6 2 Dose Level: 0.03 34.20 8.780 6 25.31 9.507 6 0.00 0.000 6 Dosage Units mg/kg/day 105514 lossis 105516 105521 MEAN S.D. N 79.55 67.38 87.16 62.83 74.23 11.141 4 1.10 5.86 0.19 9.92 4.24 4.473 4 3S.50 21.00 23.13 63.80 35.86 19.695 4 4.64 28.82 23.58 49.29 26.58 18.359 4 0.00 0.00 0.00 0.00 0.00 0.000 4 Group: Male 3 Dose Level: 0.15 Dosage units mg/kg/day 105505 105510 lossia 105523 105524 105528 MEAN S.D. N 50.93 77.93 67.52 61.48 63.60 72.30 65.61 9.320 6 4.07 0.53 0.93 1.81 0.68 6.04 2.34 2.235 6 45.97 31.51 45.46 34.64 31.45 28.17 36.20 7.651 6 18.34 17.29 25.93 27.49 16.37 13.10 19.75 5.686 6 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 THYROID STIMULATING TOTAL TRIXODOTHYRON UU/mL ng/dL --------------------------------- 0.26 0.50 0.56 0.34 1 13 0.'95 0.62 0.345 6 113.08 104.32 222.61 137.32 154.19 99.03 121.76 20.932 6 1.16 0.21 0.94 2.12 0.86 0.442 4 140.65 97.32 127.13 120.13 121.31 18.116 4 0.85 0.69 1.87 0.00 0.75 0.00 0.69 0.689 6 130.66 104.25 145.93 136.56 107.44 111.71 122.76 17.258 6 773 Appendix 6 Summary and Individual Blood Hormone Determination Day -40 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CORTISOL /ig/dL -------- TESTOSTERONE ngImL ------------ Group: Male 4 Dose Levelt 0.75 105506 105507 IOSS09 105511 105512 105522 49.42 44.53 82-95 75.12 81.05 58.08 1.27 7.01 1.03 16.78 0.14 10.11 MEAN S.D. n 65.19 16.683 6 6.06 6.565 6 Group: Female 1 Dose Level: 0 105529 105530 105531 105535 105544 105549 81.80 70.50 85.44 6!5 .06 89.56 66.75 0.41 0.01 0.25 0.37 0.44 0.15 MEAN S.D. N 79.86 9.123 6 0.27 0.168 6 Groupt Female 2 Dose Level: 0.03 105537 105541 105547 105550 79.24 108.45 67.50 89.13 0.17 0.77 0.19 0.23 MEAN S.D. N 86.09 L*7.337 4 0.34 0.288 4 ESTRAR)IOL pg/mL --------- ESTRONE pg/mL ------- ESTRIOL pg/mL ------- Dosage Unit- mg/kg/day 28.98 32.46 27.21 37.12 37.24 52.20 21.20 30.79 14.40 42.06 21.90 49.26 0.00 0.00 0.00 0.00 0.00 0.00 35.97 8.991 6 29.95 13.432 6 0.00 0.000 6 Dosage Unit: mg/kg/day 42.94 90.55 52.80 79.48 72.70 50.29 31.46 65.47 91.67 52.46 46.44 34.57 0.00 0.00 0.00 0.00 0.00 0.00 64.79 18.833 6 53.71 22.407 6 0.00 0.000 6 Dosage Unitt mg/kg/day 59.21 116.25 40.43 62.40 69.S7 32.593 4 48.11 90.73 67.42 61.31 66.89 17.818 4 0.00 0.00 0.00 0.00 0.00 0.000 4 THYROID STIMULATING UU/ML ------------------- TOTAL TRIXODOMROMI ng/dL -------------- 0.82 1.92 0.57 0.59 0.25 1.54 0.9s 0.6&3 6 0.00 0.00 0.11 0.73 2.16 0.69 0.62 0.827 6 157.93 80.90 116.45 188.61 169.66 158.85 146.73 36.914 6 75.62 128.68 73.71 125.42 106.71 76.27 97.74 25.813 6 0.01 0.26 1.14 0.93 0.59 O.S36 4 131.29 132.70 86.87 88.98 109.96 25.465 4 774 Appendix 6 Summary and Individual Blood Hormone Determination Day -40 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFMIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNMLGUS MONKEYS ANIMAL NUMBER CORTISOL pg/dL TESTOSTERONE ng/aL ---------- ESTRADIOL pg/mL --------- ESTRONE pg/mL ------- ESTRIOL pg/mL ------- THYROID STIMULATING UU/mL ------------------- TOTAL TRIZODOTHYRONI ng/dL -------------- Group: Female 3 Dose Level: 0.15 Dosage Unit: mg/kg/day 105532 105538 105539 105545 105548 105552 63.15 70.84 68.60 64.50 67.75 53.55 0.06 0.08 0.35 0.13 0.66 0.40 MEAN S.D. N 64.73 6.148 6 0.28 0.234 6 Group- Female 4 Dose Level: 0.75 33.18 53.04 492.12 114.49 75.11 45.64 29.09 40.85 272.75 81.43 55.06 48.94 0.00 0.00 0.00 0.00 0.00 0.00 135.60 176.980 6 88.02 92.1741 6 0.00 0.000 6 Dosage Unit: mg/kg/day 1.38 0.00 1.33 0.17 0.00 2.13 0.84 0.901 6 95.64 114.53 114.65 106.43 116.19 82.66 105.02 13.401 6 105533 105534 105536 105540 105542 105551 MEAN S.D. N 69.41 60.42 66.67 65.40 92.90 64.20 69.83 11.681 6 0.73 0.29 0.15 0.08 0.32 0.42 0.33 0.230 6 90.70 60.87 66.36 35.46 59.98 76.86 65.02 18.541 6 76.17 66.05 59.95 33.64 43.92 82.48 60.37 18.740 6 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 0.00 0.13 0.04 1.39 1.02 0.24 0.47 0.587 6 109.13 81.98 114.01 119.54 151.57 108.31 113.92 22.513 6 775 Appendix 6 Summary and Individual Blood Hormone Determination Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOL.GUS MONXEYS ANIMAL NUMBER ------ CORTISOL pg/dL -------- TESTOSTERONE ESTRADIOL ESTRONE ng/mL pg/ML pg/mL ------------ --------- ------- ESTRIOL pg/mL ------- THYROID STIMULATING TOTAL TRrIODOTHYltOMI UU/mL ng/dL --------------------------------- Group: Male 1 Dose Level: 0 105508 105517 105519 105520 105526 105527 59.85 50.40 74.30 55.75 72.92 67.71 2.60 2.25 0.40 3.11 0.48 2.43 MEAN S.D. N 63.49 9.676 6 1.88 1.151 6 Group: Male 2 Dose Level: 0.03 105514 105515 105516 105521 MEAN S.D. N 81.35 77.44 50.15 61.80 67.69 14.422 4 1.41 1.40 0.31 3.03 1.54 1.121 A Group- Male 3 Dose Level: 0.15 105505 105510 105518 105523 105524 105528 MEAN S.D. N 58.10 69.33 54.45 66.60 91.70 69.75 68.16 13.025 6 5.40 0.39 1.06 2.36 1.11 0.74 1.84 1.867 6 Dosage Unit: mg/kg/day 18.82 35.11 25.09 29.31 22.23 29.56 27.46 41.06 31.24 51.38 21.97 26.74 0.00 0.00 0.00 0.00 0.00 0.00 26.69 5.938 6 33.31 10.926 6 0.00 0.000 6 Dosage Unitt mg/kg/day 31.71 26.17 29.91 40.47 43.75 32.63 35.52 57.63 0.00 0.00 0.00 0.00 32.07 6.060 4 42.38 11.204 4 0.00 0.000 4 Dosage Unit- mg/kg/day 30.42 25.88 26.53 25.62 23.61 22.60 27.04 22.77 39.19 37.12 32.22 21.66 0.00 0.00 0.00 0.00 0.00 0.00 25.78 2.718 6 30.00 7.358 6 0.00 0.000 6 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 0.00 0.00 0.00 0.00 0.00 0.000 4 0 00 0:00 0.32 0.00 0.00 0.00 0.05 0.131 6 101.15 112.05 112.26 115.75 127.37 92.95 110.26 11.939 6 120.88 126.21 97.87 105.02 112.50 13.269 4 117.98 114.00 149.51 140.05 86.43 100.82 lia.13 23.608 6 776 Appendix 6 Summary and individual Blood Hormone Determination Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGus MONKEYS ANIMAL NUMBER ------ CORTISOL pg/dL -------- TESTOSTERONE ESTRADIOL ESTROME ng/ML pg/mL pg/mL ------------ --------- ------- ESTRIOL pg/mL ------- TOTAL THYROID STIMULATING TRI10DOTHYRON /iU/ML ng/dL -------------------------------- Group: Male 4 . Dose Level% 0,75 105506 105507 105509 105511 105512 105522 47.35 49.45 71.85 71.00 65.67 61.00 0.85 1.81 1.13 2.40 0.17 3.96 MEAN S.D. N 60.89 10.801 6 1.72 1.341 6 Group: Female 1 Dose Level: 0 Dosage Unit: mg/kg/day 26.15 32.25 24.92 24.62 33.79 36.25 31.68 32.53 22.42 48.45 36.30 41.15 0.00 0.00 0.00 0.00 0.00 0.00 29.66 5.047 6 35.42 8.985 6 0.00 0.000 6 Dosage Unit: mg/kg/day 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 149.78 117.94 130.15 137.80 128.50 133.19 132.89 10.581 6 105529 105530 105531 105535 105544 105549 72.55 76.75 49.35 68.60 52.84 55.44 0.28 0.07 0.50 0.35 0.42 0.07 MEAN S.D. N 62.42 11.701 6 0.28 0.179 6 Group: Female 2 Dose Level: 0.03 105537 105541 105547 105550 80.90 66.41 83.87 47.16 0.16 0.17 0.46 0.31 MEAN S.D. N 69.59 16.783 4 0.28 0.141 4 35.08 122.95 75.71 61.83 208.06 45.31 49.80 102.72 92.55 59.99 101.29 59.93 0.00 0.00 0.00 0.00 0.00 0.00 91.49 64.841 6 77.71 23.710 6 0.00 0.000 6 Dosage Unit: mg/kg/day 63.92 70.21 65.82 44.95 82.77 78.87 70.18 119.41 0.00 0.00 0.00 0.00 61.23 21.165 4 87.81 21.716 4 0.00 0.000 4 0.00 0.01 0.00 0.00 1.26 0.00 0.21 0.514 6 0.00 0.00 0.00 0.00 0.00 0.000 4 $2.65 184.14 90.39 109.23 145.88 99.05 118.56 38.982 6 167.85 119.83 284.36 110.60 170.66 79.847 4 777 Appendix 6 Summary and Individual Blood Hormone Determination Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PMKFLUOROOCTANE SULPONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL UMBER ------ CORTISOL pg/dL -------- TESTOSTERONE ESTRADIOL ESTRONE ng/mL pg/mL pg/mL ------------ --------- ------- ESTRIOL pg/mL ------- Group: Female 3 Dose Level: 0.15 105532 105538 105539 105545 105548 105552 57.80 87.05 50.45 57.66 56.95 62.72 0.18 0.09 0.08 0.03 0.59 0.54 MEAN S.D. N 62.11 12.632 6 0.25 0.248 6 Groupt Female 4 Dose Level: 0.75 105533 105534 105536 105540 105542 105551 80.05 71.00 40.50 68.05 82.95 63.39 0.55 0.19 0.16 0.05 0.37 0.19 ME" S.D. N 68.99 12.436 6 0.25 0.179 6 Dosage Unit: mg/kg/day 73.31 34.86 45.40 97.36 80.60 35.64 61.20 26.181 6 64.68 46.45 87.24 92.73 76.53 71.52 73.19 16.617 6 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 Dosage Unit: mg/kg/day 197.69 75.81 51.69 27.69 53.10 133.61 243.31 98.79 75.52 27.51 54.14 259.85 0.00 0.00 o.oo 0.00 0.00 0.00 89-93 63.894 6 126.52 99.828 6 0.00 0.000 6 THYROID STIMULATING TOTAL TRIIODOTHYROMI JJU/ML ng/dL --------------------------------- 1.98 0.00 0.00 0.00 0.00 0.09 0.34 0.802 6 0.04 0.00 0.00 0.00 0.00 0.00 0.01 0.016 6 221.66 133.62 122.82 126.61 125.43 99.82 239.33 42.411 6 298.47 161.23 130.92 94.60 124.93 119.61 154.96 73.494 6 778 Appendix 6 Summary and individual Blood Hormone Determination Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERPLUOROOCTANG SuLpoNrC ACID POTASSIUM SALT (PPOS;T-629S) IN CyNomOL(;US MotmyS ANIMAL NUMBER ------ CORTISOL jig/dL -------- TESTOSTEROME ng/mL ------------ Group: Male 1 Dose Level: 0 105508 105517 105519 105520 IOS526 105527 59.57 58.12 56.30 51.45 54.80 56.59 0.56 1.38 0.36 2.11 0.89 10.76 MEAN S.D. N 56.14 2.818 6 2.68 4.010 6 Group: Male 2 Dose Level- 0.03 105514 105515 105516 105521 MEAN S.D. N Groupi Male 72.96 56.42 53.39 60.98 2.64 0.94 0.22 10.10 60.94 8.601 4 3.48 4.532 4 3 Dose Level: 0.15 105505 105510 iossis 105523 105524 105528 61.35 66.10 52.23 61.98 64.07 73.61 0.76 0.60 0.83 2.11 0.68 1.04 HEM S.D. N 63.22 6.968 6 1.00 0.563 6 ESTRADIOL pg/mL --------- ESTROME pg/mL ------- ESTRIOI, pg/mL ------- Dosage Unit: mg/kg/day 14.21 30.66 19.61 31.75 17.02 31.22 21.01 42.28 34.97 65.4S 32.02 47.lS 0.00 0.00 0.00 0.00 0.00 0.00 24.08 8.004 6 40.48 15.181 6 0.00 0.000 6 Dosage Unit: mg/kg/day 32.81 23.69 14.32 37.38 84.41 39.25 48.23 99.72 0.00 0.00 0.00 0.00 27.05 10.218 4 67.65 28.460 4 0.00 0.000 4 Dosage Unitt mg/kg/day 23.37 24.13 26.75 27.07 15.77 10.40 36.78 29.76 39.59 44.98 33.62 23.33 0.00 0.00 0.00 0.00 0.00 0.00 21.2S 6.703 6 34.49 7.452 6 0.00 0.000 6 THYROID STIMULATING UU/mL ------------------- TOTAL TRIIODOTHYRCHI ng/dL ------ -- ----- 0.02 0.86 0.00 0.00 0.47 0.70 0.34 0.387 252.81 298.92 279.29 241.26 316.62 250.74 273.27 30.081 0.70 0.43 0.13 0.14 0.35 0.272 4 0.07 0.68 0.92 0.00 0.32 0.01 0.33 0,307 6 306.12 283.59 272.54 229.90 273.04 31.973 4 265.64 255.dl 272.85 284.01 221.20 228.32 254.57 25.007 6 779 Appendix 6 Summary and Individual Blood Hormone Determination Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULPONIC MONKRYS ANIMAL NUMBER ------ CORTISOL yg/dL -------- TESTOSTERONE ng/mL ------------ Group: Male 4 Dose Level: 0.75 105506 105507 105509 105511 105512 105522 60.57 69.37 86.47 75.68 64.22 53.06 1.13 14.80 1.24 1.50 0.25 37.59 MEAN S.D. N 68.23 11.785 6 9.42 14.866 6 Group: Female I Dose Level: 0 105529 105530 105531 105535 105544 105549 58.61 77.09 60.99 61.72 62.18 56.68 0.31 0.08 0.20 0.25 0.46 0.18 MEAN S.D. N 62.88 7.266 6 0.25 0.130 6 Group: Female 2 Dose Level: 0.03 10553'1 105541 105547 rO5550 MEAN S.D. 76.40 91.53 63.15 64.55 71.41 8.993 4 0.23 0.31 0.39 0.27 0.30 0.068 4 ESTRADIOL pg/mL --------- ESTRONE Pg/mL ------- ESTRIOL pg/mL ------- Dosage Unit; mg/kg/day 24.16 51.78 17.49 6.35 21.10 69.66 182.56 91.86 35.79 35.89 39.97 162.36 0.00 0.00 0.00 0.00 0.00 0.00 31.76 23.908 6 91.41 66.580 6 0.00 0.000 6 Dosage Unit: mg/kg/day 42.85 39.24 88.53 40.91 75.30 65.95 72.21 74.66 208.96 63.01 65.02 56.58 0.00 0.00 0.00 0.00 0.00 0.00 58.80 20.805 6 90.07 58.605 6 0.00 0.000 6 Dosage Unit: mg/kg/day 64.21 61.86 45.86 55.39 177.41 127.77 76.97 143.29 0.00 0.00 0.00 0.00 56.93 8.209 4 131.36 41.770 4 0.00 0.000 4 THYROID STIMULATING AU/ML ------------------- TOTAL TRIIODOTHYRONI ng/dL -------------- 0.00 0.36 0.66 0.14 0.04 0.03 0.21 0.259 6 229.83 199.82 259.19 230.58 246.92 270.21 239.42 25.037 6 0.18 0.69 0.27 0.40 2.61 0.21 0.73 0.941 6 256.85 189.21 211.24 267.83 216.47 236.08 229.61 29.621 6 0.00 0.01 0.68 0.27 0.24 0.319 279.90 240.82 223.65 232.10 244.12 24.864 4 780 Appendix 6 Summary and Individual Blood Hormone Determination Day 37 26-WsEx CAPSULE TOXICITY STUDY WITH PERFLUOROOCTME ACID POTASSIUM SALT (PPOS;T-6295) IN CYNONOLGUS SULPONIC MONKEYS ANIMAL NUMBER CORTISOL Ug/dL TESTOSTERONE ng/mL ------------ Group: 105532 105538 105539 105S45 105548 105552 MEAN S.D. u Group: 105533 105534 105536 105540 105542 105551 MEAN S.D. N Female 3 Dose Level: 0.15 66.39 54.30 50.23 46.45 46.73 56.82 0.20 0.07 0.08 0.09 0.30 0.49 53.49 7.537 6 0.20 0.162 6 Female 4 DoSe Level: 0.75 63.27 53.74 55.56 54.54 54.14 68.07 0.29 0.15 0.19 0.07 0.09 0.12 58.22 5.998 6 0.15 0.080 6 ESTRADIOL po/mL --------- ESTRONE pg/mL ------- ESTRIOL pg/mL ------- Dosage Units mg/kg/day 383.90 27.95 38.80 119.09 34-02 27.36 351.81 58.49 86.17 227.52 52'.35 51.92 0.00 0.00 0.00 0.00 0.00 0.00 105.17 140.935 6 138.04 124.485 6 0.00 0.000 6 Dosage Unit: mg/kg/day 70.06 49.92 42.44 31.28 67.52 104.58 150.87 123.86 63.03 47.69 67.27 271.41 0.00 - 0.00 0.00 0.00 0.00 0.00 60.97 25.978 6 120.69 83.839 6 0.00 0.000 6 THYROID STIMULATING IM/RL ------------------- TOTAL TRIIODDTHYRCHI ng/dL -------------- 1.56 0.00 1.21 0.00 0.00 0.91 0.61 0.703 6 192.15 225.80 221.63 237.82 le4.62 220.15 213.70 20.701 6 1.07 1.59 0.00 0.26 0.52 0.10 0.59 0.622 6 190.90 203.76 204.79 191.80 196.18 190.95 196.40 6.414 6 781 Appendix 6 Summary and individual Blood Hormone Determination Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTA= sULpMIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYIMOLGus Motn=S AN114AL NUMBER CORTISOL m/dL TESTOSTERONE ESTRADIOL ng/ML pg/mL ------------ --------- ESTRONE pg/mL ------- ESTRIOL pg/mL ------- Gro up: Male 1 Dose Level: 0 Dosage Unit: mg/kg/day 105508 105517 105519 105520 105526 105527 MEAN S.D. N 64.62 57.71 60.20 50.13 63.25 43.13 56.51 8.318 6 0.50 1.30 0.39 2.28 0.65 1.40 1.09 0.719 6 17.70 35.89 27.43 27.41 15.13 38.03 26.93 9.256 6 28.21 51.07 24.22 69.97 34.66 42.05 41.70 16.877 6 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 Groupt Male 2 Dose Level- 0.03 Dosage Unit: mg/kg/day 105514 IOSS15 105516 105521 MEAN S.D. N 86.10 59.33 49.45 62.77, 64.41 15.522 4 2.10 0.67 0.27 3.13 1.54 1.318 4 29.19 27.02 17.22 44.97 29.60 11.494 4 71-76 53.19 77.85 95.20 74.50 17.333 4 0.00 0.00 0.00 0.00 0.00 0.000 4 Group: Male 3 Dose Level: 0.15 Dosage Unit: mg/kg/day 105505 105510 105518 105523 105524 105526 MEAN S.D. N 70.82 58.68 60.80 76.60 62.76 63@38 65.51 6.813 6 1.07 0.51 0.77 2.83 0.94 0.77 1.15 0.845 6 34.40 25.73 31.30 35.79 21.61 14.54 27.23 8.199 6 36.91 26.22 30.11 62.53 31.79 33.29 36.01 13.086 6 0.00 o.od 0.00 0.00 0.00 0.00 0.00 0.000 6 THYROID STIMULATING TOTAL TRIXODOTHYROMI bU/ML ng/dL ------------------- -------------- 0.25 1.72 0.00 0.00 0.00 1.42 0.57 0.790 6 0.54 0.11 0.47 0.57 0.42 0.213 4 119.34 163.61 145.97 164.61 139.41 135.30 144.71 17.407 6 147.03 143.03 118.77 148.62 139.36 13-929 4 1.22 1.53 2.85 0.00 0.00 0.29 0.98 1.118 6 131.32 117.68 167.15 166.99 135.36 131.96 141.74 20.528 6 782 Appendix 6 Summary and Individual Blood Hormone Determination Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ANIMAL NUMBER ------ CORTISOL ug/dL -------- TESTOSTERONE ng/mL ------------ ESTRADIOL pg/ML --------- ESTRONE pg/mL ------- ESTRIOL pg/mL ------- THYROID STIMULATING IM/mL ------------------- TOTAL TRIIODOTHYRONI ng/dL --------------- Group% male 4 Dose Level: 0.75 IOSSOG 105507 105509 105511 105512 105522 70.92 69.36 80.21 83.50 69.38 65.14 0.61 2.05 1.10 1.52 0.19 1.87 MEAN S.D. N 73.09 7.137 6 1.22 0.728 6 Dosage Unit: mg/kg/day 6.89 14.27 8.28 4.43 20.03 30.27 84.83 50.89 33.16 43.47 35.68 56.44 0.00 0.00 0.00 0.00 0.00 0.00 14.03 9.757 6 50.75 18.886 6 0.00 0.000 6 0.00 0.33 0.97 0.00 0.00 0.00 0.22 0.392 6 110-61 96.11 120.78 133.14 121.31 142.07 120.67 16.237 6 Group: Female 1 Dose Level: 0 105529 105530 105531 105535 105544 105549 73.17 80.23 63.57 77.78 72.02 67.18 0.25 0.03 0.23 0.29 0.24 0.11 MEAN S.D. N 72.33 6.264 6 0.19 0.100 6 Dosage Unit; mg/kg/day 42.49 40.60 97.01 135.19 110.97 88.68 95.52 73.45 154.45 166.44 116.03 104.97 0.00 0.00 0.00 0.00 0.00 0.00 84.16 37.377 6 118.48 35.602 6 0.00 0.000 6 2.88 0.32 0.00 0.00 3.86 0.10 1.19 1.718 6 86.34 157.85 105.00 104.25 94.26 141.85 114.93 26.369 6 Group: Female 2 Dose Level: 0.03 Dosage Unit: mg/kg/day 105537 105541 105547 105550 MEAN S.D. N 75.87 88.44 67.51 72.45 76.07 8.934 4 0.24 0.30 0.41 0.42 0.34 0.087 4 97.35 95.89 71.56 63.70 82.13 17.053 4 171.29 128.24 149.12 160.39 152.26 18.393 4 0.00 0.00 0.00 0.00 0.00 0.000 4 0.00 0.09 1.74 0.00 0.45 0.856 4 170.52 124.69 122.85 116.15 135.55 28.879 4 783 Appendix 6 ANIMAL NUMBER ------ Summary and Individual Blood Hormone Determination Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT IPPOS;T-6295) IN CYNOMOLGUS MONKEYS CORTISOL pg/dL -------- TESTOSTERONE ng/mL ESTRADIOL pg/mL --------- ESTRONE pg/aL ------- ESTRIOL pg/mL ------- THYROID STIMULATING UU/ML ------------------- TOTAL TRIIODOTHYRONI ng/dL -------------- Group: Female 3 Dose Level.- 0.15 105532 105538 105539 105545 105548 105552 63.46 62.14 65.91 60.86 48.14 61.25 0.05 0.06 0.00 0.05 0.36 0.44 MEAN S.D. N 60.29 6.228 6 0.16 0.189 6 Group: Female 4 Dose Leveli 0.15 105533 105534 105536 105540 105542 105551 68.36 67.55 73.98 73.87 66.81 113.15 1.04 0.05 0.12 0.09 0.40 0.10 MEAN S.D. N 77.29 17.850 6 0.30 0.384 6 Dosage Unit: mg/kg/day 196.89 40.91 50.54 142.62 60.76 60.28 162.41 57.31 122.72 226.73 96.83 85.06 0.00 0.00 0.00 0.00 0.00 0.00 92.00 63.048 6 125.18 61.195 6 0.00 0.000 6 Dosage Unit: mg/kg/day 539.64 21.16 53.49 47.69 414.10 98.43 637.44 92.30 103.29 87.57 248.93 208.43 0.00 0.00 0.00 0.00 0.00 0.00 195.75 222.733 6 229.66 210.776 6 0.00 0.000 6 3.00 0.00 1.30 0.00 0.48 0.13 0.82 1.176 6 1.64 1.91 0.17 0.00 0.69 0.00 0.74 0.849 6 100.87 122.69 109.98 147.17 99.01 102.13 113.64 18.596 6 92.49 104.34 101.67 102.37 04.83 95.64 95.22 8.753 6 784 Appendix 6 Summary and Individual Blood Hormone Determination Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER CORTISOL jig/dL TESTOSTERONE ESTRADIOL ng/ML pg/aL ------------ --------- ESTRONE pg/mL ------- ESTRIOL pg/mL ------- THYROID STIMULATING TOTAL TRIIODOTHYRONI UU/mL ng/dL ------------------- -------------- Group: Male 1 Dose Level: 0 Dosage Unit": mg/kg/day 105508 105517 Io5sl9 105520 105526 105527 63.12 72.02 68.04 50.11 60.09 48.19 0.65 1.78 0.44 2.53 0.96 1.57 3.16 22.72 14.07 19.55 16.52 35.93 20.61 53.30 30.76 65.61 29.74 51.35 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 141.51 162.07 144.10 148.94 161.62 162.45 MEAN S.D. 60.26 9.547 6 1.32 0.786 6 Group: Male 2 Dose Level: 0.03 18.66 10.784 6 41.90 17.359 6 0.00 0.000 6 Dosage Unit: mg/kg/day 0.00 0.000 6 153.4S 9.720 6 105514 105515 105516 105521 70.30 48.85 58.29 64.30 1.86 0.96 0.34 10.76 29.08 29.88 28.37 41.20 82.17 40.06 40.27 107.46 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 166.24 148.07 151.67 146.06 MEAN S.D. N 60.44 9.148 4 3.48 4.893 4 32.13 6.076 4 67.49 33.199 4 0.00 0.000 4 0.00 0.000 4 153.01 9.120 Group- Male 3 Dose Level: 0.15 Dosage Unit: mg/kg/day 105505 r05510 105518 105523 105524 105528 MEAN S.D. N 63.97 58.44 52.27 64.33 73.62 72.47 64.18 8.157 6 1.54 1.05 0.90 2.03 0.02 0.73 1.18 0.506 6 17.57 20.81 20.88 20.84 13.64 21.33 19.18 3.040 6 37.08 34.69 26.72 47.88 34.88 23.84 34.18 8.478 6 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 0.00 0.00 0.17 0.00 0.00 0.00 0.03 0.069 6 143.76 141.60 156.52 174.10 119.61 143.77 146.56 18.023 6 785 Appendix 6 Summary and Individual Blood Hormone Determination Day 91 ANIMAL NUMBER CORTISOL Pg/dL 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAKE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYN M LGUS MONKEYS TESTOSTERONE ng/mL ------------ ESTRADIOL pg/mL -- ------ ESTRONE pg/ML --- --- ESTRIOL pg/mL ---- -- THYROID STIMULATING UU/mL ------------------- TOTAL TRIIODOTHYRONI ng/dL ------------- Group: Male 4 Dose Level: 0.75 105506 105507 105509 105511 105512 105522 73.97 49.60 86.62 60.08 64.66 67.73 0.48 2.71 1.73 1.70 0.26 1.87 HEM S.D. N 67.11 12.571 6 1.46 0.923 6 Groups Female 1 Dose Level: 0 105529 105530 105531 105535 105544 105549 74.49 69.78 50.36 62.89 70.71 65.26 0.55 0.06 0.30 0.29 1.05 0.32 MEAN S.D. N 65.58 8.513 6 0.43 0.342 6 Group: Female 2 Dose Level: 0.03 105537 105541 105547 105550 75.93 99.16 68.67 61.58 0.30 0.37 0.38 0.28 MEAN S.D. 73.89 11.748 4 0.33 0.050 4 Dosage Unit: mo/kg/day 2.29 22.58 4.65 3.05 13.32 19.66 48.87 40.22 34.03 38.67 33.13 57.55 0.00 0.00 0.00 0.00 0.00 0.00 10.93 8.875 6 42.08 9.438 6 0.00 0.000 6 Dosage Unit% mg/kg/day 59.28 30.39 76.52 126.05 218.24 85.32 96.58 37.67 104..81 94 . 80 115 65 89.15 0.00 0.00 0.00 0.00 0.00 0.00 99.30 66.222 6 89.61 27.146 6 0.00 0.000 6 Dosage Unit: mg/kg/day 276.11 88.60 48.03 34.29 579.38 143.46 87.11 106.94 0.00 0.00 0.00 0.00 111.76 111.968 4 229.22 234.602 4 0.00 0.000 4 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 0.00 0.00 0.00 0.00 0.00 0.000 4 107.40 89.57 127.61 144.57 102.29 136.40 117.97 21.468 6 95.65 200.64 117.41 144.43 160.65 139.16 142.99 36.187 6 161.68 144.58 121.55 160.17 147.00 19.641 4 786 Appendix 6 Summary and Individual Blood Hormone Determination Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLOUS MONKEYS ANIMAL NUMBER ------ CORTISOL jig/dL -------- TESTOSTERONE ESTRADIOL ESTRONE ng/mL pg/mL pg/ML ------------ --------- ------- ESTRIOL pg/mL ------- Group: Female 3 Dose Level: 0.15 105532 105538 105539 105545 105548 105552 53.44 54.36 56.38 50.87 46.19 55.40 0.07 0.09 0.01 0.00 0.30 0.38 MEAN S.D. N 52.77 3.737 6 0.14 0.159 6 Group: Female 4 Dose Level: 0.75 105533 105534 105536 105540 105542 105551 63.67 57.80 71.04 85.09 50.02 91.43 0.51 0.04 0.14 0.26 0.23 0.42 MEAN S.D. N 71.18 14.229 6 0.27 0.174 6 Dosage Units mg/kg/day 208.42 55.31 48.35 64.59 29.92 74.01 161.28 71.47 96.47 142.80 64.58 74.24 0.00 0.00 0.00 0.00 0.00 0.00 80.10 64.629 6 101.81 40.773 6 0.00 0.000 6 Dosage Units mg/kg/day 162.24 34.90 29.06 42.06 95.90 394.36 186.20 67.09 60.95 65.39 72.08 503.53 0.00 0.00 0.00 0.00 0.00 0.00 126.42 140.697 6 159.21 175.397 6 0.00 0.000 6 THYROID STIMULATING TOTAL TRZIODOTHYRON pU/mL ng/dL -------------------------------- 0.09 0.00 0.00 0.00 0.00 0.00 0.02 0.037 6 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 '120.33 113.79 114.24 113.45 109.64 92.26 110.62 9.628 6 95.87 81.56 92.51 90.84 81.86 83.67 87.72 6.129 6 787 Appendix 6 Summary and Individual Blood Hormone Determination Day 102 26-WEEX CAPSULE TOXICITY STUDY WITH ACID POTASSIUM SALT (PFOS;T-6295) PERFLUOROOCT^NE IN CYNOMOLGUS SULPONIC MONXEYS ANIMAL NUMBER CORTISOL Pg/dL TESTOSTERONE ng/ML ------------ Group: Male I Dose Level % 0 105508 105517 105519 105520 105526 105527 49.36 44.88 54.72 37. 96 60.22 39.62 0.80 0.99 0.41 3.20 0.91 2.05 MEAN S.D. n 47.79 8.681 6 1.38 1.049 6 Group: Male 2 Dose Level: 0.03 105514 105515 105516 105521 57 .72 41.90 43.62 53.31 1.43 0.44 0.31 8.03 MEAN S.D. N 49.14 '1.613 4 2.55 3.686 4 Group: Male 3 Dose Level: 0.15 105505 iossio 105518 105523 105524 105528 42.54 39.10 46.25 57.87 51.67 !52.89 0.25 2.63 0.70 2.06 0.73 0.42 MEAN S.D. N 48.39 7.014 6 1.13 0.973 6 ESTRADIOL pg/mL --------- ESTRONE Pg/mL ------- ESTRIOL pg/mL ------- Dosage Unit: mg/kg/day 11.03 26.64 21.40 19.07 15.79, 43.81 16.55 34.19 24.00 35.67 22.56 46.79 0.00 0.00 0.00 0.00 0.00 0.00 22.96 11.485 6 29.96 10.990 6 0.00 0.000 6 Dosage Unit: mg/kg/day 29.26 9.14 16.57 41.46 65.16 29.60 29.96 70.45 0.00 0.00 0.00 0.00 24.11 14.242 4 48.79 22.060 4 0.00 0.000 4 Dosage Unit: mg/kg/day 28.98 25.43 28.63 26.43 20.26 9.63 21.56 19.76 25.41 39.59 20.89 13.61 0.00 0.00 0.00 0.00 0.00 0.00 23.23 7.363 6 23.47 8.774 6 0.00 0.000 6 THYROID STIMULATING PU/ML ------------------- TOTAL TRIIODOTHYROMI ng/dL -------------- 0.01 1.43 0.48 0.35 0.30 0.02 0.43 0.524 6 0.76 0.32 0.11 0.15 0.34 0.298 4 1.10 0.51 2.09 0.18 0.09 0.46 0.74 0.751 6 153.39 155.85 152.78 168.92 162.99 164.16 159.67 6.579 6 140.24 133.97 77.19 117.72 119.28 30.705 4 134.08 110.87 136.26 144.20 114.48 107.88 124.63 15.36S 6 788 Appendix 6 Summary and Individual Blood Hormone Determination Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOUIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOWLGUS NOMEYS ANIMAL NUMBER CORTISOL pg/dL TESTOSTEROME ng/mL ------------ Group: Male 4 Dose Level: 0.75 105507 105511 105512 105522 59.90 43.70 70.20 59.49 2.10 0.69 0.04 1.80 MEAN S.D. N 58.32 10.935 4 1.16 0.961 4 Group: Female I Dose Level: 0 105529 105530 105531 105535 105544 105549 65.21 74.89 35.19 74.58 61.62 41-85 0.17 0.01 0.03 0.52 0.34 0.02 MEAN S.D. N 58.89 16.743 61 0.18 0.209 6 Group: Female 2 Dose Level- 0.03 105537 105541 105547 105550 MEAN S.D. N 76.03 61.45 39.39 59.31 59.05 1!5. 063 4 0.29 0.13 0.26 0.14 0.21 0.082 4 ESTRKDIOL pg/mL --------- ESTRONE pg/ML ------- ESTRIOL pg/mL ------- Dosage Unit. mg/kg/day 0.00 1.01 0.'00 2.00 0.75 0.958 4 33.59 27.68 22.69 36.89 30.21 6.298 4 0.00 0.00 0.00 0.00 0.00 0.000 4 Dosage Units mg/kg/day 232.49 47.22 51.65 318.47 162.44 78.63 351.64 66.58 77.36 239.29 153.92 61.78 0.00 0.00 0.00 0.00 0.00 0.00 148.48 110.143 6 158.76 116.512 6 0.00 0.000 6 Dosage Unit: mg/kg/day 254.69 47.66 41.73 156.72 492.79 101.86 164.10 364.55 0.00 0.00 0.00 0.00 125.20 201.227 4 280.83 180.363 4 0.00 0.000 4 THYROID STIMULATING IJU/ML ------------------- TOTAL TRIXODOTIFYROM ng/dL ------------- 1.59 0.34 0.59 1.18 0.93 0.566 4 1.33 0.00 0.00 0.06 2.75 0.22 0.73 1.115 6 0.00 0.09 0.65 1.77 0.68 0.824 4 58.09 97.68 34.06 75.57 66.35 26.941 4 95.65 183.66 215.47 139.41 152.04 12S.36 135.27 30.6S9 6 148.10 131.20 98.77 102.12 120.05 23.70,3 4 789. Appendix 6 Summary and Individual Blood Hormone Determination Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ANIMAL NUMBER ----- CORTISOL ug/dL -------- TESTOSTERONE ng/mL ------------ Group: Female 3 Dose Level: 0.15 105532 105538 105539 105545 105548 105552 47.71 36.38 42.82 48.24 32.13 48.26 0.01 0.04 0.00 0.04 0.03 0.16 MEAN S.D. N 42.59 6.904 6 0.05 0.058 6 Groupt Female 4 Dose Level: 0.75 109533 105534 105536 105540 105542 105551 63.42 66.38 51.73 60.27 56.03 96.30 0.17 0.05 0.09 0.15 0.19 0.07 MEAN S.D. N 65.69 15.876 6 0.12 0.058 6 ESTRADIOL pg/mL --------- ESTRONE pg/mL ------- ESTRIOL Pg/ML ------- Dosage Unit: mg/kg/day 197.86 45.10 52.30 52.62 39.61 36.02 141.98 64.69 100.79 74.46 51.74 60.51 0.00 0.00 0.00 0.00 0.00 0.65 70.59 62.705 6 82.36 33.716 6 0.11 0.265 6 Dosage Unit: mg/kg/day 36.11 9.45 0.00 47.41 93.61 52.80 55.31 37.27 53.37 60.05 115.82 99.85 0.00 0.00 0.00 0.00 0.00 0.00 39.90 33.589 6 70.28 30.505 6 0.00 0.000 6 THYROID STIMULATING UU/ML --------- --------- 4.33 0.25 0.89 0.62 0.98 0.57 1.27 1.520 6 2.31 1.10 0.62 0.21 0.55 0.22 0.64 0.793 6 TOTAL TRIIODOTHYRONI ng/dL ------------- 90.44 100.45 106.11 86.22 103.15 93.10 96.58 7.824 6 83.76 81.38 76.41 71.65 92.22 104.92 85.06 11.963 6 790 Appendix 6 Summary and Individual Blood Hormone Determination Additional Collection - Terminal Sacrifice ANIMAL NUMBER ------ 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLTIOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TOTAL TRIIODOTHYRONINE FREE TRIIODOTHYRONINE TOTAL THYROXIN ng/dL pg/mL pg/dL ---------------- ---------------- -------- FREE THYROXIN ng/dL -------- Group: Male 1 Dose Level: 0 105509 105519 105527 126.89 110.98 107.16 5.18 3.61 3.83 MEAN S.D. N Groupt Male 115.01 10.464 3 2 Dose 4.21 O.BSO 3 Level: 0.03 105514 105515 IOSS16 105521 MEAN S.D. N 111.98 103.61 120.14 106.40 110.53 7.299 4 5.14 4.58 5.44 5.36 5.13 0.388 4 Group: Male 3 Dose Level: 0.15 Dosage Unit: mg/kg/day 3.46 2.73 3.56 1.02 0.86 1.15 3.25 0.453 3 1.01 0.145 3 Dosage Unitt mg/kg/day 3.97 3.01 4.11 4.31 1.07 1.10 1.16 1.50 3.05 0.577 4 1.21 0.199 4 Dosage Unit: mg/kg/day 105510 105518 105524 105528 HEM S.D. N 95.90 93.03 86.79 100.26 94.00 5.649 4 4.19 4.41 3.88 4.85 4.33 0.408 4 2.88 2.49 2.38 3.07 2.71 0.324 4 1.02 0.93 0.79 1.01 0.94 0.106 4 791 Appendix 6 Summary and Individual Blood Hormone Determination Additional Collection - Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ANIMAL NUMBER ------ TOTAL TRIIODOTHYRONINE FREE TRIIODOTHYRONINE TOTAL THYROXIN ng/dL Pg/ML Ug/dL ---------------- ---------------- -------- FREE. THYROXIN ng/dL --------- Group: Male 4 Dose Level: 0.75 105506 105507 105512 59.28 55.46 13.96 2.74 3.07 1.55 MEAN S.D. N 42.90 25.135 3 2.45 0.800 3 Group: Female I Dose Level: 0 105530 105531 105535 105544 131.98 87.43 98.97 104.98 5.33 3.10 3.48 4.28 MEAN S.D. N 105.82 18.899 4 4.05 0.986 4 Group: Female 2 Dose Level: 0.03 105541 105547 105550 109.59 81.34 86.09 4.13 3.14 3.49 MFAN S.D. N 92.34 15.127 3 3.59 0.502 3 Dosage Unit: mg/kg/day 4.90 3.16 1.83 1.36 1.15 0.86 3.30 1.540 3 1.12 0.251 3 Dosage unit: mg/kg/day 5.50 2.62 4.93 3.52 1.43 0.78 1.17 0.86 4.14 1.313 4 1.06 0.299 4 Dosage unit: mg/kg/day 4.24 3.41 2.80 1.32 0.86 0.85 3.48 0.723 3 1.01 0.269 3 792 Appendix 6 Summary and Individual Blood Hormone Determination Additional Collection - Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH ACID POTASSIUM SALT (PFOS;T-6295) ANIMAL NUMBER ------ TOTAL TRIIODOTHYRONINE FREE TRIIODOTHYRONINE TOTAL THYROXIN FREE THYROXIN ----n-g/-d-L-------------I->g-/-M-L ---------p-g-/-d-L--- ng/dL --------- Group: 105532 105538 105545 105548 MEAN S.D. N Female 3 Dose Level: 0.15 74.72 77.02 72.24 94.86 3.27 2.99 2.96 3.87 79.71 10.287 4 3.27 0.424 4 Dosage Unitt mg/kg/day 3.03 1.89 2.71 3.88 1.04 0.59 0.90 1.06 2.88 0.823 4 0.90 0.217 4 Group: 105534 105536 105540 105551 MFJW S.D. N Female 4 Dose Levelt 0.75 51.14 59.03 60.77 64.05 2.88 2.43 3.13 2.83 58.75 5.482 2.82 0.290 Dosage unit% mg/kg/day 4.52 3.87 2.04 3.30 1.49 1.00 0.79 1.03 3.43 1.054 1.08 0.295 PERFLUOROOCTANS IN CYNOMOLGUs SULFMIC mommys 793 Appendix 6 Summary and Individual Blood Hormone.Determination Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT iPFOS;T-6295) IN CYNOMOLGUS SULPONIC MONKEYS ANIMAL NUMBER CORTISOL Pg/dL -------- TESTOSTERONE ng/mL ------------ ESTRADIOL Pg/ML --------- ESTROME po/mL ------- ESTRIOL pg/mL ------- THYROID STIMULATING PU/IAL------------------- TOTAL TRIIODOTHYRONI ng/dL -------------- Group: Male 1 Dose Level; 0 105520 105526 38.18 44.16 2.66 2.51 MEAN S.D. N 41.17 4.228 2 2.59 0.106 2 Group: Male 3 DoSe Level: 0.15 IOSS05 105523 27.26 52.61 0.99 3.84 MEAN S.D. N 39.94 17.925 2 2.42 2.015 2 Group: Male 4 Dose Level: 0.75 105511 105522 51.54 44.31 4.72 5.36 MEAN S.D. n 47.93 5.112 2 5.04 0.453 2 Dosage Unit: mg/kg/day 17.90 10.98 64.49 25.43 0.00 0.00 14.44 4.893 2 44.96 27.620 2 0.00 0.000 2 Dosage Unit: mg/kg/day 17.56 21.73 32.66 59.98 0.00 0.00 19.65 2.949 2 46.32 19.318 2 0.00 0.000 2 Dosage Unitt mg/kg/day 0.00 27.09 37.83 70.81 0.00 0.00 13.55 19.156 2 54.32 23.320 2 0.00 0.000 2 1.61 2.12 1.87 0.361 2 1.21 0.97 1.09 0.170 2 1.67 1.05 1.36 0.438 2 159.60 183.22 171.41 16.702 2 154.43 164.81 159.62 7.340 2 165.18 129.72 147.45 25.074 2 794 Appendix 6 Summary and Individual Blood Hormone Determination Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER CORTISOL jig/dL TESTOSTERONE ESTRADIOL ESTRONE ng/ML pg/mL pg/mL ------------ --------- ------- ESTRIOL pg/mL ------- TOTAL THYROID STIMULATING TRIIODOTHYRONI /M/RL ng/dL --------------------------------- Group: Female I Dose Level; 0 105529 54.69 40.39 0.96 0.12 MEAN S.D. N 47.54 10.112 2 0.49 0.523 2 Group: Female 3 Dose Level: 0.15 105539 105552 57.55 59.07 0.10 0.82 MEAN S.D. N 58.31 1.075 2 0.46 0.509 2 Group: Female 4 Dose Level: 0.75 105533 105542 55.91 66.34 0.61 0.37 MEAN S.D. N 61.13 7.375 2 0.49 0.170 2 Dosage Unit. mg/kg/day 53.08 43.63 83.74 64.84 0.00 0.00 48.36 6.682 2 74.29 13.364 2 0.00 0.000 2 Dosage Unit: mg/kg/day 44.04 68.85 71.13 88.81 0.00 0.00 56.85 16.978 2 79.97 12.502 2 0.00 0.000 2 Dosage Unit: mg/kg/day 133.46 88.23 289.99 154.68 0.00 0.00 110.85 31.982 2 222.34 95.679 2 0.00 0.000 2 1.78 1.66 1.72 0.85 2 1.88 0.59 1.24 0.912 2 1.76 1.56 1.66 0.141 2 116.20 133.52 124.86 12.247 2 114.34 121.25 117.80 4.886 2 99.29 101.57 100.43 1.612 2 795 Appendix 6 Summary and Individual Blood Hormone Determination Day 245 ANIMAL NUMBER ------ CORTISOL pg/dL -------- 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS:T-6295) IN CYNOMOLGUS SULFCNIC MONKEYS TESTOSTERONE ng/ML ------------ ESTRADIOL pg/mL --------- ESTROUR pg/mL ------- ESTRIOL pg/mL ------- THYROID STIMULATING /iU/mL ------------------- TOTAL TRIIODOTHYRONI ng/dL -------------- Group: Male I Dose Level: 0 105520 105526 52.17 44.90 2.83' 1.40 MEAN S.D. N 48.54 5.141 2 2.12 1.011 2 Group: Male 3 Dose Level: 0.15 105505 105523 46.88 54.44 0.50 7.18 MEAN S.D. N 50.66 5.346 2 3.84 4.723 2 Group: Male 4 Dose Leveli 0.75 105511 105522 37.08 25.17 1.55 2.99 MEAN S.D. N 31.13 8.422 2 2.27 1.018 2 Dosage unit: mg/kg/day 40.85 16.61 79.85 31.48 0.00 0.00 28.73 17.140 2 55.67 34.203 2 0.00 0.000 2 Dosage Unit: mg/kg/day 23.84 25.40 43.65 59.41 0.00 0.00 24.62 1.103 2 51.53 11.144 2 0.00 0.000 2 Dosage Unit: mg/kg/day 17.97 26.57 53.06 77.43 0.00 0.00 22.22 6.152 2 65.25 17.232 2 0.00 0.000 2 0.25 0.00 0.13 0.177 2 0.10 0.00 0.05 0.071 2 0.67 0.33 0.50 0.240 2 171.00 133.39 152.20 26.594 2 154.84 151.74 153.29 2.192 2 170.42 137.27 153.85 23.441 2 796 Appendix 6 Summary and Individual Blood Hormone Determination Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYMOMOLGUS MONKEYS AN114AL NUMBER ------ CORTISOL jig/dL -------- TESTOSTERONE ng/mL ------------ ESTRADIOL pg/mL --------- ESTRONE pg/mL ------- ESTRIOL pg/mL ------- THYROID STI14ULATIMG #U/mL ------------------- TOTAL TRIIODOTHYROMI ng/dL -------------- Group.- Female 1 Dose Level.- 0 105529 105549 56.47 43.54 0.12 0.07 MEAN S.D. N 50.01 9.143 2 o.id 0.035 2 Group: Female 3 Dose Level: 0.15 105539 105552 63.10 60.29 0.07 0.28 MEAN S.D. N 61.70 1.987 2 0.18 0.148 2 Group: Female 4 Dose Level: 0.75 105533 105542 62.75 81.69 0.66 0.06 MEAN S.D. N 72.22 3.3.393 2 0.36 0.424 2 Dosage Unit: mg/kg/day 38.61 112.14 95.66 115.58 0.00 0.00 75.38 51.994 2 105.62 14.086 2 0.00 0.000 2 Dosage Unit: mg/kg/day 61.24 88.08 137.78 94.05 0.00 0.00 74.66 19.979 2 115.92 30.922 2 0.00 0.000 2 Dosage Elnitt mg/kg/day 257.61 114.63 255.84 120.11 0.00 0.00 186.12 101.102 2 187.99 95.976 2 0.00 0.000 2 0.68 0.98 0.93 0.212 2 0.81 0.00 0.41 0.573 2 1.04 0.82 0.93 0.156 2 130.32 136.09 133.21 4.080 2 127.17 142.77 134.97 11.031 2 118.99 121.98 120.49 2.114 2 797 Appendix 6 Summary and Individual Blood Hormone Determination Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH VERPLUOROOCTANE SuLPONrc ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOROLGUS MMKRYS ANIMAL NUMBER COETTISOL Ug/dL TESTOSTERONE ESTRADIOL ESTRONE ng/mL pg/ML pg/mL ------------ --------- ------- ESTRIOL pg/ML ------- Group: Male 1 Dose Level: 0 105520 105526 34.89 45.23 1.76 1.40 MEAN S.D. N 40.06 '7.311 2 1.58 0.255 2 Group: Male 3 Dose Level: 0.15 105505 105523 42.95 62.34 3.64 2.55 Dosage Unit: mg/kg/day 17.17 14.11 15.64 2.164 2 62.84 34.27 48.56 20.202 2 0.00 0.00 0.00 0.000 2 Dosage Unit: mg/kg/day 25.06 25.26 39.86 63.44 0.00 0.00 MEAN S.D. N 52.10 13.074 2 3.10 0.771 2 25.16 0.141 2 51.65 16.674 2 0.00 0.000 2 Group: Male Dose Level: 0.75 105511 105522 MEAN S.D. N 59.62 26.17 42.90 23.653 2 2.36 4.12 3.24 1.245 2 Dosage Unit- mg/kg/day 6.94 30.46 51.42 83.94 0.00 0.00 18.70 16.631 2 67.68 22.995 2 0.00 0.000 2 TOTAL THYROID STIMULATING TRIZODOTHYRONI #U/mL ng/dL ---------------------------------- 0.00 0.02 0.01 0.014 2 0.25 0.00 0.13 0:177 2 0.24 0.09 0.17 0.106 2 134.97 167.54 151.26 23.030 2 146.70 161.73 154.22 10.628 2 163.13 163.73 163.43 0.424 2 798 Appendix 6 Summary and Individual Blood Hormone Determination Day 274 26-WEEK CAPSTJLE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYN M LGUS MONKEYS ANIMAL NUMBER ------ CORTISOL ug/ dL -------- TESTOSTERONE ng/ML ------------ ESTRADIOL pg/mL --------- ESTRONE pg/ML ------- ESTRIOL pg/mL ------- THYROID STIMULATING UU/mL ------------------- TOTAL TRIXODOTHYRONI ng/dL --------------- Group- Female 2. Dose Level: 0 105529 105549 MEAN S.D. N 64.71 47.01 55.86 12.516 2 0.44 0.02 0.23 0.297 2 Dosage Unitt mg/kg/day 43.91 42.07 115.88 57.38 0.00 0.00 42.99 1.301 2 86.63 41.366 2 0.00 0.000 2 0.00 0.68 0.34 0.481 2 91.10 130.21 110.66 27.655 2 Group: Female 3 Dose Level: 0.15 105539 105552 45.77 44.48 0.04 0.18 MEAN S.D. N 45.13 0.912 2 0.11 0.099 2 Groui): Female 4 Dose Level- 0.75 Dosage Unit: mg/kg/day 48.03 114.70 127.24 124.21 0.00 0.00 81.37 47.143 2 125.73 2.143 2 0.00 0.000 2 Dosage Unit- mg/kg/day 0.29 0.00 0.15 0.205 2 114.25 103.46 108.86 7.630 2 105533 105542 MEAN S.D. N 49.13 63.28 56.21 10.006 2 0.49 0.40 0.45 0.064 2 109.08 108.09 108.59 0.700 2 153.99 128.04 141.02 18.349 2 0.00 0.00 0.00 0.000 2 0.64 0.01 0.33 0.445 2 115.86 85.17 100.53 21.715 2 799 Appendix 6 Summary and Individual Blood Hormone Determination Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ANIMAL NUMBER ------ CORTISOL #g/dL -------- TESTOSTERONE ESTRADIOL ESTRONE ng/ML pg/mL pg/mL ------------ --------- ------- ESTRIOL pg/mL ------- THYROID STIMULATING #rJ/mL ----------- TOTAL FREE TRIIODOTHYRONINE TRIIODOTHYRONINE T ng/dL pg/aL ---------------- ---------------- Group2 Male 1 Dose Level: 0 Dosage Unit: mg/kg/day 105520 105526 49.93 54.85 1.68 1.47 22.29 12.73 66.72 34.79 0.00 0.00 MEAN S.D. N 51.89 4.186 2 1.58 0.148 2 17.51 6.760 2 50.76 22.578 2 0.00 0.000 2 Group; Male 3 Dose Level: 0.15 Dosage Unit: mg/kg/day 0.00 0.08 0.04 0.057 2 113.68 167.98 140.83 38.396 2 4.34 6.23 5.29 1.336 2 105505 105523 35.82 56.14 0.16 2.50 21.68 21.64 35.93 55.20 0.00 0.00 MEAN S.D. N 45.98 14.368 2 1.33 1.655 2 21.66 0.028 2 45.57 13.626 2 0.00 0.000 2 Group: Male 4 Dose Levelt 0.75 Dosage Unit: mg/kg/day 0.15 0.00 0.08 0.106 2 141.49 150.29 145.89 6.223 2 4.68 5.39 5.04 0.502 2 105511 105522 MEAN S.D. N 52.62 27.46 40.04 17.791 2 1.59 1.66 1.63 0.049 2 0.00 14.90 7.45 10.536 2 43.71 66.78 55.25 16.313 2 0.00 0.00 0.00 0.000 2 0.01 0.05 0.03 0.028 2 145.00 116.61 130.81 20.075 2 4.78 4.24 4.51 0.382 2 800 Appendix 6 Summary and individual Blood Hormone Determination Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS ANIMAL NUMBER ------ CORTISOL ug/dL -------- TESTOSTERONE ESTRADIOL ESTRONE ng/mL pg/mL pg/mL ------------ --------- ------- ESTRIOL pg/mL ------- THYROID STIMULATING UU/ML ----------- TOTAL FREE TRIIODOTHYRONINE TRIIODOTHYRONINE ng/dL pg/mL ---------------- ---------------- Groups Female I 105529 105549 60.74 55.31 MEAN S.D. N 58.03 3.840 2 Group: Female 3 105539 105552 MEAN S.D. N 54.81 61.78 58.30 4.929 2 Dose Level :0 0.66 0.04 93.93 67.50 0.35 0.438 2 80.72 18.689 2 Dose Level: 0.15 0.00 0.15 46.03 78.67 0.08 0.106 2 62.35 23.080 2 Dosage Unit: mg/kg/day 136.07 78.68 0.00 0.00 0.14 0.22 107.38 40.,581 2 0.00 0.000 2 0.18 0.057 2 Dosage unit: mg/kg/day 127.28 179.51 153.40 36.932 2 0.00 0.00 0.00 0.000 2 0.00 0.33 0.17 0.233 2 95.57 102.40 98.99 4.830 2 102.53 06.79 94.66 11.130 2 3.84 3.31 3.58 0.375 2 2.30 2.66 2.48 0.255 2 Group: Female 4 105533 105542 40.44 66.14 MEAN S.D. N 53.29 18.173 2 Dose Level: 0.75 0.02 0.03 95.89 95.19 0.03 0.007 2 95.54 0.495 2 Dosage units mg/kg/day 182.57 116.98 0.00 0.00 0.85 0.00 149.78 46.379 2 0.00 0.000 2 0.43 0.601 2 127.50 94.51 111.01 23.327 2 4.40 2.64 3.52 1.245 2 801 Appendix 6 Summary and Individual Blood Hormone Determination @ Day 364 ANIMAL NUMBER ------ 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTAME ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS CORTISOL ug/dL -------- TESTOSTERONE ng/ML ------------ ESTRADIOL ESTRONE pg/mL pg/ML --------- ------- ESTRIOL pg/ML ------- THYROID STIMULATING UU/mL ----------- TOTAL FREE TRIZODOTHYRONINE TRIIOD(YRHYRONINE T ng/dL pg/ML ---------------- ---------------- Group: Male 1 Dose Level: 0 Dosage .Unit: mg/kg/day 105520 105526 56.87 50.92 2.87 2.98 31.48 22.18 71 33 39.48 0.00 0.00 MEAN S.D. N 53.90 4.207 2 Groupt Male 3 Dose 2.93 0.078 2 26.83 6.576 2 55-.41 22.521 2 0.00 0.000 2 Level: 0.15 Dosage Unit: mg/kg/day 105505 105523 35.11 69.91 S.86 3.19 27.97 21.80 33.61 59.64 0.00 0.00 MEAN S.D. N 52.51 24.607 2 4.53 1.888 2 24.89 4.363 2 46.63 18.406 2 0.00 0.000 2 Group: Male 4 Dose Level: 0.75 Dosage Unit: mg/kg/day 105511 105522 53.56 42.27 2.07 1.90 12.59 22.13 50.72 61.86 0.00 0.00 MEAN S.D. N 47.92 7.983 2 2.03 0.064 2 17.36 6.746 2 56.29 7.877 2 0.00 0.000 2 0.00 0.01 0.01 0.007 2 0.15 0.00 0.08 0.106 2 0.00 0.00 0.00 0.000 2 142.33 173.51 157.92 22.048 2 141.33 136.42 138.88 3.472 2 189.73 142.92 166.33 33.100 2 4.92 5.87 S.40 0.672 2 4.17 4.73 4.45 0.396 2 6.84 6.13 6.49 0.502 2 802 Appendix 6 Summary and individual Blood Hormone Determination Day 364 ANIMAL NUMBER ------ 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS WONKEYS CORTISOL TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL ug/dL ng/mL Vg/ML pg/mL lpg/ML -------- --------------------- ------- ------- THYROID STIMULATING lei/RL ---------- TOTAL FREE TRIIOD(YRHYROMINE TRIIODOTHYRONINE ng/dL pg/mL -------------------------------- Group: Female 1 105529 105549 56.92 54.02 MEAN S.D. N 55.47 2.051 2 Group: Female 3 105539 105552 48.00 74.04 MEAN S.D. N 61.02 18.413 2 Group: Female 4 105533 105542 61.92 89.59 MEAN S.D. N 75.76 19.566 2 Dose Levelt 0 Dosage Unit: mg/kg/day 0.36 0.01 0.19 0.247 2 46.66 72.28 59.47 18.116 2 106.07 120.53 113.30 10.225 2 0.00 0.00 o.oo 0.000 2 0.38 0.00 0.19 0.269 2 Dose Level: 0.15 Dosage unit: mg/kg/day 0.01 0.13 53.88 25.95 120.92 71.07 0.00 0.00 0.12 0.39 0.07 0.085 2 39.92 19.749 2 96.00 35.249 2 0.00 0.000 2 0.26 0.191 2 Dose Level: 0.75 Dosage unit: mg/kg/day 0.13 0.07 166.75 164.57 352.52 175.61 0.00 0.00 0.28 0.00 0.10 0.042 2 165.66 1.541 2 264.07 125.094 2 0.00 0.000 2 0.14 0.198 2 114.22 94.96 104.59 13.619 2 113.58 89.22 101.40 17.225 2 108.62 105.87 107.25 1.945 2 3.48 2.75 3.12 0.516 2 2.73 3.99 3.36 0.091 2 3.84 3.34 3.59 0.354 2 803 Appendix 6 Summary and Individual Blood Hormone Determination Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH ACID POTASSIUM SALT (PPOS;T-6295) PERFLUOROOCTAKE IN CYNOMOLGUS SULFONIC MONKEYS ANIMAL NUMBER ------ CORTISOL Ug/dL -------- TESTOSTERONE ng/mL ------------ ESTRADIOL ESTRONE pg/ML pg/mL --------- ------- ESTRIOL pg/mL ------- THYROID STIMULATING PU/mL ----------- TOTAL FREE TRIIODOTHYRONINE TRIIODOTHYRONINE T ng/dL pg/mL ---------------- ---------------- Group: Male I Dose Level: 0 Dosage unit: mg/kg/day 105520 105526 45.28 42.55 3.12 2.03 24.62 20.60 33.29 17.89 0.00 0.00 MEAN S.D. N 43.92 1.930 2 2.59 0.771 2 22.61 2.843 2 25.59 10.889 2 0.00 0.000 2 Group; Male 3 Dose Level: 0.15 Dosage Unit: mg/kg/day 105505 105523 35.05 58.45 5.77 4.15 33.45 34.94 15.52 31.76 0.00 0.00 MEAN S.D. N 46.75 16.546 2 4.96 1.146 2 34.20 1.054 2 23.64 11.483 2 0.00 0.000 2 Group: Male 4 I)ose Level: 0.75 Dosage Unit: mg/kg/day 105511 105522 34.37 18.72 2.19 5.27 15.15 32.89 34.29 47.97 0.00 0.00 MEAN S.D. N 26.55 11.066 2 3.73 2.178 2 24.02 12.544 2 41.08 9.603 2 0.00 0.000 2 4.00 3.18 3.59 0.580 2 3.02 2.40 2.71 0.438 2 2.70 2.67 2.69 0.021 2 160.85 ise.ei 159.83 1.442 2 156.75 189.99 173.37 23.504 2 200.22 142.75 171.49 40.637 2 7.90 5 7.34 3 7.62 4 0.396 1 2 2 5.12 4 8.58 4 6.05 4 2.447 2 8.55 6.89 7.72 1.174 2 804 Appendix 6 Summary and Individual Blood Hormone Determination Day 456 ANIMAL NUMBER ------ 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS SULFONIC MONKEYS CORTISOL ug/dL -------- TESTOSTERONE ESTRADIOL ng/mL %>g/ML ------------ --------- ESTRONE pg/mL ------- ESTRIOL pg/mL ------- THYROID STIMULATING /IU/ML ----------- TOTAL FREE TRIIODOTHYRONINE TRIIODOTHYRONINE T ng/dL pg/mL ---------------- ---------------- Group.- Female 1 105529 105549 61.24 45.43 MEAN S.D. N 53.34 11.179 2 Group: Female 3 105539 105552 59.18 40.35 MEAN S.D. N 49.77 13.315 2 Group: Female 4 105533 105542 52.84 88.82 MEAN S.D. N 70.83 25.442 2 Dose Level: 0 Dosage Unitz mg/kg/day 0.75 0.16 60.82 58.64 62.11 17.39 0.00 0.00 3.41 2.27 0.46 0.417 2 59.73 1.541 2 39.75 31.622 2 0.00 0.000 2 2.84 0.806 2 Dose Level: 0.15 Dosage Unit: mg/kg/day 0.06 0.15 111.82 63.26 73.29 56.27 0.00 0.00 5.31 5.26 0.11 0.064 2 87.54 34.337 2 64.78 12.035 2 0.00 0.000 2 5.29 0.035 2 Dose Level: 0.75 Dosage unit: mg/kg/day 0.73 0.30 101.24 180.10 06.37 115.95 0.00 0.00 5.20 4.19 0.52 0.304 2 140.67 55.762 2 101.16 20.916 2 0.00 0.000 2 4.70 0.714 2 131.39 127.08 129.24 3.048 2 127.44 104.90 116.17 15.938 2 140.68 147.41 144.05 4.759 2 6.12 5.03 5.58 0.771 2 4.32 5.02 4.67 0.495 2 4.86 4.23 4.55 0.445 2 805 Appendix 6 Summary and Individual Blood Hormone Determination Day 546 ANIMAL NUMBER ------ 26-WEEK CAPSULE TOXICITY STUDY WITH ACID POTASSIUM SALT (PFOS;T-6295) PERFLUOROOCTANE IN CYNOMOLGUS SULFONIC MONKEYS CORTISOL Ug/dL -------- TESTOSTERONE ESTRADIOL ESTRONE ng/ML pg/mL pg/mL ------------ --------- ------- ESTRIOL pg/mL ------- THYROID TOTAL FREE STIMULATING TRIIODOTHYRONINE TRIIODCYTHYRONINE T UU/mL ng/dL pg/mL ----------- ---------------- ----- ---------- Group: Male 1 Dose Level: 0 Dosage Unit% mg/kg/day 105520 105526 41.44 48.80 3.51 2.29 19.03 21.13 35.81 22.20 0.00 0.00 MEAN S.D. N Groupt 45.12 5.204 2 Male 3 Dose 2.90 0.863 2 Level: 0.15 20.08 29.01 1.485 9.624 2 2 Dosage Unit: 0.00 0.000 2 mg/kg/day 105505 105523 43-54 55.25 2.03 4.77 22.13 33.60 11.11 27.76 0.00 0.00 MEAN S.D. N 49.40 0.280 2 3.40 1.937 2 27.87 8.111 2 19.44 11.773 2 0.00 0.000 2 Group: Male 4 Dose Level: 0.75 Dosage Unit: mg/kg/day 105511 105522 31.74 17.51 6.17 6.28 27.18 30.18 34.39 40.74 0.00 0.00 MEAN S.D. N 24.63 10.062 2 6.23 0.078 2 28.68 2.121 2 37.57 4.490 2 0.00 0.000 2 3.01 3.34 3.18 0.233 2 3.11 3.17 3.14 0.042 2 1.92 3.36 2.64 1.018 2 141.17 144.88 143.03 2.623 2 127.36 164.68 146.02 26.389 2 211.71 133.42 172.57 55.359 2 5.57 5.51 5.54 0.042 2 4.68 7.26 5.97 1.824 2 7.91 6.19 7.05 1.216 2 806 Appendix 6 Summary and Individual Blood Hormone Determination Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PPOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CORTISOL jig/dL -------- TESTOSTERONE ESTRADIOL ESTRONE ng/mL pg/ML pg/mL ------------ --------- ------- ESTRIOL pg/mL ------- THYROID TOTAL FREE STIMULATING TRIIODOTHYRONINE TRIIODOTHYRONINE T UU/mL ng/dL pg/ML ----------- ---------------- ---------------- Group: Female 1 io5529 105549 61.95 50.10 MEAN S.D. N 56.03 8.379 2 Group: Female 3 105539 105552 58.68 26.08 MEAN S.D. N 42.38 23.052 2 Group: Female 4 105533 iO5S42 49.05 82.98 MEAN S.D. N 66.02 23.992 2 Dose Level: 0 Dosage Unit: mg/kg/day 0.32 0.15 88.86 55.18 60.95 29.70 0.00 0.00 2.28 2.86 0.24 0.120 2 72.02 23.815 2 45.33 22.097 2 0.00 0.000 2 2.57 0.410 2 Dose Level: 0.15 Dosage Unit; mg/kg/day 0.22 0.18 249.40 228.31 112.37 104.83 0.00 0.00 4'.32 2.22 0.20 0.028 2 238.86 14.913 2 108.60 5.332 2 0.00 0.000 2 3.27 1.485 2 Dose Level: 0.75 Dosage Unit: mg/kg/day 0.73 0.40 89.07 94.97 85.47 46.34 0.00 0.00 3.89 4.50 0.57 0.233 2 92.02 4.172 2 65.91 27.669 2 0.00 0.000 2 4.20 0.431 2 113.93 122.28 118.11 5.904 2 133.88 194.67 164.28 42.985 2 122.53 131.85 127.19 6.590 2 4.61 4.59 4.60 0.014 2 ONS 7.69 7.69 1 4.63 4.36 4.50 0.191 2 807 APPENDIX 7 CellProliferatioRneport Covance 6329-223 3M T-6295.7 Note: This appendixcontainsinformationsuppliedand auditedby Pathology AssociatesInternation(aPlAI). 808 Covance 6329-223 3M T-6295.7 Asiri&.w_j Pathology Assoclafes lntemadonal A CompanoyfScienAcpeplicatlfnotnesmatCiotnpaolrarion DRAFT CELL PROLIFERATION REPORT 26-WEEK CAPSULE TOMCrrY STUDY WrM PERFLUOROOCTANE SULFONIC ACED POTASSIUM SALT (PFOS; T-6295)IN CYNOMOLGUS MONIKEYS COVANCE STUDY NUMBER 6329-223 PREPARED FOR: 3M TO]ACOLOGY SERVICES BUILDING 220-2E-02,3M CENTER ST. PAUL, MN 55144-1000 PREPARED BY-. PATHOLOGY ASSOCIATES INTERNATIONAL 15 WORMANIS MELL COURT, SUITE I FREDERICIC, MD 21701 FEBRUARY 25,2000 15 Worman's MRI Court,SuiteI FrederickM,aryland 21701 * (301)663-1644 (301)663-8"4 FAX 809 3M T-6295.7 DraftCellProlifamdcmRqmri Covance StudyNumber 6329-223 Page 2 TABLE OF CONTENTS L CELL pROLInRATION IL TABLES IIL SIGNATURE PAGE iv. QUALITY ASSURANCE V. APPENDIX I REPORT STAYEMENT sio 3M T-6295.7 DrafCteUProUfantioRneport CovanceSoldyNumber6329-2Z Page3 CELL PROL]IFERATION REPORT 26-WEEKCAPSULE T03aCITY STUDY WrM PERFLUOROOCTANE SULFONIC ACID POTASSRM SALT (PFOS; T-6295)IN CYNOMOLGUS MON%ZYS COVANCE STUDY NTUNMER 6329-223 PURPOSE Ihe pmpose of the study was to assessthe affectof the testmaterialon criticaelnzyme levels, homones, and other selectedbiochemical parameters when r-yn=olgus monkeys for atleast26 weeks. dailyby capsule to Miis repom submitted by Pathology Awociates Internationa(lPAI) to the study Sponsor, 3M, representsthe cellproliferatiofnindingsand interpretatiofnor Covance Study Number 6329-223 entitled"26-Week Capsule ToxicityStudy with Perfluomoctone SulfonicAcid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys". AU aspectsof the tasksassociatedwith PAI's portion of thisstudy were conducted in compliance with the Environmental ProtectionAgency Good Laboratory Practice(GLP) Regulationsas setforthin Title40 of theUS Code of Federal Regulations,Part 792, issuedNovember 29, 1993 (eitectivDeecember 29, 1983),and with any applicableamendments. MATERL4LS AND BWMODS Tissue Collectionfor CeH Proliferation Four animals per sex in groups I - 4 were sacrificedafterat least26 weeks on study. A rqmentative sample of the liver,testes(males only) and pancreas from each animal was fixed in fonnalin,processed and embedded to pamf:finblock by Covance per protocolspecifications. Tissue blocks were then shipped to PAI forsectioningand staining.From each block, a slide ,was prepared for H&E evaluationand in=unohistochemical detectionof proliferatingcell nuclearantigen(PCNA), a marker ofcellproliferation. Immunohistochemistry for CellProliferation Sectionsof pamffin-embedded tissueswere cut at approximately5 gm and placed an positively chuged slides(SuperfrosPtlus,FisherScienfifiPci,ttsburghP,A) to ensureadhesionduring processingfor PCNA. Standard immunohistochemical methods were used to staintissuesfor PCNA (PAI's Standard Operating Procedure for Immunohistochemical Staining (SOP #707). Briefly,tissuesectionswere incubatedwith a monoclonal antibody to PCNA (DAKO, lot 4107(101),PAI No. A2240) and reagentsrequiredforthe avidin-biotipneroxidase(ABC Kit,lot :#PK6102, PAI No. K444) method for the detectionof the antigen-antibodycomplex. PCNA expression in cellswas localizedby the chromagen 3,3'-diaminobenzidine(DAB; Sigma Chemical Co., lot #49H8204 & 108H8210). Tissue sectionswere wunterstained with h=atoxylin. 811 3M T-6295.7 DnftCeUProHfcmtioRnqxnt CovanceSt* Number6329-223 Page4 CeH ProlfferatioMneasurements The p=entage ofhepatocytesinS-phaseOabolingindex,LI)was determinedby scoringatleast 3000 hepatocytesin 10 fieldsof liver.T"ne LI in the testes(males only) was detennined by scoring the numba of PCNA-positive Leydig cell'asmong at least100 Leydig cells. The labelingindex in the pancreaswas scoredsubjectivelwyith 4 beingboth acinarand islet@daftied heavily and 3 being predominant stainingin the acinarregion.A negative controlslidewas included in the stainingrun aad consistedof study tissuethatwas not incubated with the primary antibody. For ceU proliferatioenvaluations,slideswere f= perused atlow magnification(IOOX) tojudge qualityof staining,processingand sectioning,potentialpatternsof cellularproUfm2don, and histomorphologic changes. Cellproliferatiownas then quantifiedathigher magnification(20OX for liverand pancreas,and 40OX for testes)as describedabove. HLrtomorphology was further assessed by evaluatingthe H&B slideprepared from the same tissueblock for each animal evaluatedfor cellproliferation. StatisticaAlnalysis The Studenf s f-test(two-sided,unequal variance)was used to testfor statisticaslignificancein Ll between controland treatmentgroups using Mcrosoft Excel version5.0. A P value of 0.05 wasjudged to be statisticalsliygnificant. RESULTS CellProlffemtion Individualanimal cellproliferatiodnataare presentedin Section]I(Table I). Cellproliferation in the liver,testesand pancreas of controland testmaterial-treateadnimals was similar. Histopathology Sections from the same tissueblocks used forpreparationof PCNA-stained slideswere stained with hernatoxylinand eosin (H&E) for histopathologiecvaluationto facilitattehe interpretation of the immunostained slides.Individualanimal findingsarepresentedin Appendix 1. Single sectionsof liver,pancreas,and testesfrom 16 adultmale monkeys and singlesectionsof liver and pancreas from 16 adult female monkeys representingcontrol,low-dose (0.03 mg/kg/day), mid-dose (0.IS mg/kg/day) and high-dose(0.75 mgtkg/day) treatmentgroups were evaluated histologically.Each tissuesectionwas stainedwith hematoxylin and eosin. The purpose of thisevaluationwas to determine whether or not morphologic changes were occurring in these tissueswhich may alteror confound the specificitoyf the PCNA stainingobserved in these -qnim:ils. 812 3M T-6295.7 DraftCeU ProHfmdon Report Covance Sb* Number 6329-223 Page 5 Tne results showed that no significantchanges were observed in either the liver,pancreas, or testiculatrissuesfrom male monkeys or the liverand pancreas tissuesfrom female monkvyr., @@ch would alterthe interpretatioonf thePCNA stainingin thisstudy. DISCUSSION In the presentstudy,cellproliferationwas measured witbinthe liver,testesand pancreas of male monkeys, and the liverand pancreas of female monkeys from control(0 mglkgtday), low dose (0.03mg/kg(day),mid-dose (0.15mg/kglday) and high dose (0.75ing/kg/day)groups after26 weeks on study to assessthe effectof the testmaterialon criticaelnzyme levels,hormones, and otha selectedbiologicalparameters,includingcellproliferation. 7here did not appear to be a cellproliferativreesponse to the testmaterialin the Hver, mstes or pancreas,as determined by labelingindices,which were similarin allanimals. SUAEMIARY In the present study,cellproliferationa,s deterzninedby measuring the labelingindex, was not increasedin the liver,testesor pancreas of monkeys. 813 3M T-6295.7 Dmft CellProHforatwnReport Covance Study Number 6329-223 13.TABLE Legend SEM Standard Error of the Mean 814 TABLE 1-1.CELL PROLIFERATION IN MONKEY$ COVANCE 3M T-6295.7 STUDY NO. 6329-223 I I Animal Lobelingindox Labolingindox Labollnglndox Does Group sex/Groua Number I Panemas I Tutes 0 mc/kglday(Co 1) 0 mgAg/day (ControD F/I 105530 F/I 1105631 0.000%@ 0.02rA 1 41 NP 31 NP 0 mg/kg/day(Contmi) F/I !:105635 0.000%! 31 NP 0 mgkg/day (Control) i F/I itow" 0.199OAi 4 NP IM*an 0.057%1 3.5 !SEM 0.048%1 0.3 0.03 mgJkg/day(Low dose) F/2 1105537 0.1130/e, 3 NP 0.03 mg/kWday (Low dose) i F/2 10-9641 0.125%1 4 NP 0.03 mg/kg/day(Low dose) F/2 .105547 0.000%1 3 NP 0.03 mg/kg/day(Low dose) F/2 105650-- 0.212%1 3 NP imean 0.112%1 3.3 ISEM 0.044%1 0.3 0.15mgikgtft (Middose) F/3 ',1105632 0.000%! 3. NP 0.IS mg/kg/day(Middose) 0.15mglkglday(Middose) 0.15 mg/kg/day(Middose) F/3 1105= F/3 1105545 F/3 11OW48 !Mean 0.086% 3 NP 0.029%11 3 NP 0.120% i 4 NP 0.069%1 3.3 ISEM 0.31 0.75 mglkglday(Highdose F/4 1105534 0.000% 0.75Mg/kRLday (Highdose) F/4 1105536 0.313% 0.75 mg/kg/day(Highdose) F/4 105540 0.000% 0.75 mg/kWday (H!ghdose) F/4 105551 0.000%1 Mean .__0.078%1 SEM 0.078%1 0 mg/kWday (Contro4 M/i 105508 0.100%) 0 ffig/kg/d(aCyontrol) 0 mg/kg/day (Contro@ wi 105517 1 Mi 0.062%1 0.108%1 0 (Control) M/I 105527 0.464%1 ,Mean 0.1846/91 ISEM 0.03mg/kglday(Low dose) M/2 1105514 0.095%1 0.03 mSAgiday (Low dose) M/2 1106615 0.000%i 0.03mgAg/day (Low dose) M/2 105516 0.00(r/ol 0.03 mRLkWdi (Lowdoes)._ M/2 105521 o.ooo%l. Mean 0.024%1 0.15 mgikglday(Middos!q I M/3 0.15mg/kglday(Middo") M/3 SEM 105510 105518 0.024Y.1 O.OMGAI 0.029%1 0.15mg/kCday(Midd se)-@- M/3 1105524 0.155%! 3 NP 3 NP 3 NP 3 MP 3.0 0.0 4 3 3 20.750/a 4 19.23% 3Z 14.63% 0.31 3.12% 3 16.36% 3 1B.SrA 3 22.95% 4 12.38% 3.3 17.55% 0.3 2.20% 3 9.17% 4 17.14% 3 14.42% 0.15 mglkg/day(Middose) M/3 1105528 0.000%,, 41 10.71% mean --665-9./7. 3.51 12.86% 0.75mg&glday (Highdose) 0.75 mg/ka@day (Highdose) 0.75mgLkg/day (Highdo e) I 0.75mg/kglday(Highdosa) i M/4 M/4--M/4 :1105506 1105507 !1105509 iIO5512 lmean !,SEM 0.034%- 0.. .0.2..7.%.P., 0.000%, 0.019%! 0.009%! 0.3! 1.80% 31 7.69% 19.61% NPI_ NP 3 ND 3.01 13.65% 0.01 5.96% ND, notdetermineddue to suboptimalstaining NP, slidenotpresent Uver Percentageof hepatocytesInS-phise Pancreas:Scored subjecdvelyvath4-i3leta3nd acinarstainedheavily(>500/loabeled)3;-acinar>islets ITestes:Percentage ofpmliferafinLgeydigcells Page 1-1 815 3M T-6295.7 Dnft Ceu Prolifmdon Report Covance StadyNumber 6329-223 IH.SIGNAIIM PAGE 26-Week Capsule To3dcityStudy with PerfluorooctaneSulfonicAcid Potassium Salt (PFOS; T-6295)inCynomolps Monkeys (CovanceStudy Number 6329-223) Submittedby-. PAI ProjectManager. SandraIL Eldridge,Ph.D. Date PAI ProjectPathologist CarolynMoyer, D.V.M.,Diplomate,A.C.V.P. Date 816 3M T-6295.7 Dmft CeU PmlifentionRqxnt Covance StadyNuinber 6329-223 TV. QUALITY ASSURANCE STATENMNT 817 3M T-&95.7 PathologyAssociateslntemational AComp&VofScrenceAppftrafforisintenmtfonalCorporatlon CellProliferatRieopnort 26-WeekCapsuleToxicitSytudywithPerfluorooctaSnuelfoniAccid PotassiuSmalt(PFOS;T-6295i)nCynomolgusMonkeys CovancSetudNyumber6:329-223 QUALITY ASSURANCE STATEMENT Miis cellproliferatipornojecthas been inspecteadnd auditedby the PAI Quality AssuranceUnit(QAU) as requirebdy theGood LaboratorPyractic(eGLP) regulations promulgatedby the U.S. EnvirommentaPlrotectioAngency (TSCA). The cell proliferatrieopnortisanaccuratreeflectiofntherecordedata.ne followintgableisa recordoftheinspections/audpietrsformedand reportedby theQAU. Date of Inspection 12106/99 02/17/00 02117100 Phase Insi)ected Date FindingsReportedto PAI Manaaement/ProiectManaeer PrimaryAntibodyDilution Study Dataand SupportingDocumentation DraftCellProliferatRieopnort 12/06/99 02/17/00 02/17/00 Karen E.Butler Dati QualityAssuranceOfficer 818 15 Worman's MillCourt,SuiteI Frede(ickM,arylan2d1701 (301)663-1644o (301)663-8994FAX Covance 6329-223 3M T-6295.7 DraftCeU ProlifemtiOnRePOrt Covance StudyNumber 6329-223 APPENDIXI 819 IndividualAnimal Findings 3M T-6295.7 3mp 06329-223 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACIID POTASSIUM SALT (PFOS; T6295) IN CYNOMOLGUS MONKEYS AND4AL NUMBER SEX DOSE GROUP HISTOLOGIC FINDINGS 105330 F IOSS31 F 10353S F 105544 F IOSS37 F 105541 F IOSS47 F 105550 F 105532 F 105538 F 105545 F 105548 F 105534 F IOSS36 F 105540 F iosssi F ID3508 Pi 105517 m 105519 m ZOSS27 m IOSS14 m iossis m 105516 m 105521 m 105510 m I Liver- NSF Pancreas-NSF I Liver-NSF Pa=reu -NSF I liver-du=gc intlu=adon, minimal Pancreas- NSF I liver- NSF Pancreas- NSE 2 liver-NSF Pancreas-NSF 2 liver-chronicinflammation,minimal Pancreas- NSF 2 Liver- NSF Pancreas- NSP 2 liver- NSF Pancreas -NSF 3 Liver-NSF Pancreas- NSF 3 Liver-chronicinflumnationm,inirral Pancreas- NSF 3 Liver- chronicinflmmmdon. minimal Pancreas- NSF 3 liver- chronicinflunmationm.inirnal Pancreas- NSF 4 I:tvcr-NSP Pancreas -NSF 4 liver- fatinfiltraticoenn,trilobulamro,derate Pancreas- NSF 4 Liver- NSF Pancreas- NSF 4 Liver- NSF , Pancreas- NSF b1 raver - chronimc inflammation, ;MniM Pancreas-chronicinflammatim minimal Testes- NSF I Liver - NSF Pancreas - NSF Testes- crush anifact,focal I Liver - NSF Pancreas - NSF Testes - NSF I Liver - NSF Pancreas - NSP Teste-sNSF 2 Liver -chronicinflammation, minimal Pancreas - chronic inflwnmation, minimal Testes - NSP 2 liver- chronicintlammation,minimal Pancreas - NSF Testes -NSF 2 Liver - NSF Pancreas - NSF Testes -NSF 2 Liver - NSF Pancreas - NSF Testes - NSF 3 liver- chronic inflammation,minimal Pancreas -NSE Testes - NSF 820 Legend: NSP = no significanftindings IndividualAnimal Findings %,ovancooci.@-AZO 3M T-6295.7 3MP #6329@-223 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFOMC POTASSIUM SALT (PFOS; T629S) IN CYNOMOLGUS MONKEYS ACED ANIMAL NUMBER SEX DOSE GitOUP HISTOLOGIC FINDINGS iossis m IOSS24 m 105528 m 105507 m IOSS12 m IOSS06 m 105509 m 3 Liver- NSP Pancreas- NSF Testes- NSF 3 Liver- NSF Pancreas- NSP Testes- NSF 3 Liver- NSF Pancreas- NSF Testes- NSF 4 Liver-fatinfjlftdocne,ntrilobumloadre,rate Pancreas- NSF Testes- NSF 4 liver- NSF Pancreas- NSP Testes- NSF 4 Liver- NSF Pancreas- NSF Testes- NSF 4 No microscopisclidesavailable. (Inventorsyhows blockssubmittedS;TPR does notshow blockssectioned.) 821 Legend: NSF no signiricarnitndings