Document 5b5rJyOxqxQkYvp7My6m15405

ARRR6 _ 3275 457 -_ --_ `TRADE SECRET Ma26~ 327 oDuwroen ssess Study Title H-24678: Two-Week Inhalation Toxicity Study in Male Rats Laboratory Project ID: DuPont-8685 AUTHOR: David P. Kelly, B.S. STUDY COMPLETED ON: April 2, 2003 ~ PERFORMING LABORATORY: E.L du Pont de Nemours and Company Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 Work Request Nome J) SERVICE CDENow (7 ~~ CompanySaniized. Doss not cantain 756A 5 TT ew R HOHLTN:TToaoVWeesk bdoiinnTToossyStutyynimbdoRs --_ oDwupeess `GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT `This study was conducted in compliance Laboratory Practice Standards except for with U.S. EPA TSCA (40 CFR part 792) Good the item documented below. The item listed does not impact the validity of the study. The test substance is commercially available and was characterized by the supplier prior to the lpinaeibrtofiraoatrtimooernoydfautnnhddiesirtssGteuoxdopy.edriLAeannbcoaernawatilotyrshyisaPnrwaaalcystzipicrneogvSittdhaeinsdd.acrhdeAsml,itcbhaaolsu,egwdheotnhheaovcuherarn`akocntroeewralisezodangtietooonfdwotuahbsetpnotehtreforming `validity of the analysis. Applicant / Sponsor: WE.iLlmdiunPgotnotndDe eNelmvouers19a8n9d8Company USA. ~ StudyDirector David onc ly, BS. QAMo> Date Applican/t Sponsor: TT DuboniRepresemative - Date ~~ Company Sanitized. Does not contain TSCA CB H24678:Tws o Wee ekInhao lation Tlonoiclityy SSuudbinnMMalleRReass -- QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 24678 Dates of Inspections: Protocol: August 2, 2002 Conduct: August 58,13, 2002 Records, Reports: March 3-7,11, 2003 Dates Findings Reported to StudyDirector: March 20,2003 ~ Management: March 26, 2003 Duwroowns655 Reporeaby: QuMaliatytAsTshuFrreeonneizsweAlu,dit8o5.r 2Dp : -2003 --_ -Y ompany Sanilized. Dossnot cuss tau LF22467756: TTwoooWWeeeckk iInbblsasiionnTTosiclgySStuuiddyyiinniMMatleeyRRaass -- Dpuuproonmsse8t5s. CERTIFICATION `We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. EGliar l << Pict ResWacrDheisinmoBesriAPsaCtVbAlTogntd Msgr 28-Mag-zoy ee seBairodiFonrigne Madi. , ViRaernch hen 2-fpar-2003 EvaluAattioon RnepPorttieldovgpy ohn tin DAT PhoKe -200 --~ Pip DilRonsse ACV,Po Pubes vAanmatoionn incipal Pathologist PestReviewb" y: evDoamenACsV 2 Lpb:i|-2a03 SirRes abl Approved by: No Nooin h e 2 Da -ARiL-.2003 IssuedbyStudy Director: ARep-- o3s5 2-RM=GL- 2043 . - CompanySanilzed. Dossnol contain TSCA GB 2H-02746%78::TTwwooWWeeeekkIIhnwhalloaitoinonTTooxriciictiyySSutdudyyininMMaalleeRRaattss __ -- TAOFBCOL NTEE NTS DDuuPPoomns8i6s8s5. Page GOOD LABORATORY PRACTICE COMPLIANCE STATccoE. MENT CQEURATLIIFTIYCAATSISOUNRc ANCE STATEMENT o c vers s een LIST OF TABLES ccs] LIST OF FIGURES css LIST OF APPENDICES wccrrssissmsssssssmessasosssssessssssssmsnsmsesne STUDY INFORMATION css) STUDYPERSONNEL ccna10 BET INTRODUCTION... 13 STUDY DESIGN crs13 --~ MATA.ERTIOSASLSUABNSDAMNETCHEODS r co ev s e s rs1144 BCeo AARIRMDA SUSc DA os r ms os s I. TemporaryAnimalIdentifaindcation QUATANNG..........c.rro 14 omer 14 23. AHOUSvINGRoiomEmnvriaroo.nlment... ---- 4. Anima SelectionandPermanent lenificaion .. resm------ A14 rem it 65.. HF ealtAhOMWORaOTR OTA... cere 1D. InhalationEXPOSUTE SYSIEM..veossreonnss n--_--S ee 16 21.. 3. CAhTaOmSbPeRrGCIoEnsGtrEucEtiRonOaNnd.....vD.esriegns.r.e. ee EXPOSE MOGE rrr -- emt -- 16 ertetampm-- ie E. 2C1. ThP esAt Sa TuSbsiaazt necCDeOoSAIi afGmIpCElThiOl AnrIgMODNniedrAZAnMavOalSyvsPtiRsE.iIR.o..n.........uooererernA r--r16, E. B3.odEnyviWreoingmhetntsaalnMdoCnliitnoircianlgO..D.SSIVAONS m-- cm cocoons 1 17 G. BOO FIUOINGABIES H. Clinical Pathology EVAIAUON cc ....e .eeos eess ssmses esos I. Hematolog.y " ---- ererernrrmm er 17 1T88 23.. ClUirniincaallysCihse.misty... 4. Recovery........... -wo rt p-- --a-- tg---- - --dB ren ~ 1 J. SAUnAaStHoCmAi!c PAaNtIhYOSIEOSgYc EVIUAHON r vecs es ososnsnoes 19 21 - Company Sanitized. Does not urna 15 vl HL24675: e TwoWeo ek Inhn alationTToxoiciytySStuuddyyiinnMMaalleeRRtass -- TABLE OF CONTENTS (Continued) DuDPuopmos8s6s85s Page RESULTS AND DISCUSSION ccna22 In-LAi.feCAhDafmibaelrMAEtmAoSsUphReErDe.C.on.centrationsofH-24678 and Chamber Environmental 22 B.. BCoOdNyBWOeNigShts and Clinicas l ODSGIVAHOr NS .....e ..oocurmre osos 2232 B10A0.d FBIIUOOOTAIFEIUAODHANIEYSANSGIo YSIS vne omr s sees2233 ClinAicalHPOaMtBhoIlOoIgyOBEVYAlUatcionom rns snm es esos m 232.3 B.. C. CUHHRCCAV!OCHUEM.ISUYc .ooe rrs srss sse mses nsneemes eos s en2234 D. EB. P120d2 UIE5FIOR2 E... COMCIUSIONS oor semen 24 24 --~ AnaAteomMicOPatMhoAlogYy .EVsANZsHOeNmccsvvvsvreossssssssssssssssmesssssssesnsosnessmmssssssrenso22s8n4 Bu OIGAN WEIGHS vrosseemsosmsesoses eso C. DD. GMIIOCSISOSOCBOPSIECIFVAIOMNASINGS.r.rrvervsnmsrmosmmsmoesesemesns 24 24 25 Ee CONCIUSIONS.rrrsinssomemsoseneoeesoso 23 CONCLUSIONS corsa26 RECORDS AND SAMPLE STORAGE wc 2] REFERENCES voesrssnsissssssmssssssssssssssnssssssmssonemsm2n] TABLES cosmos29 FIGURES ccs sss 14 APPENDICES cmos18 --~ - `Sompany Sanitized.Does not contain TSCA CBL HL24675: TwoWeek InhalToxaicttyiStoudny inMale Rts DuPont 8685 -- LI OFTSABLTES Page I. CHAMBERCONCENTRATIONSOF H-24G7S. . . . rremmsssmmmm-- 2. PARTICLE SIZEDISTRIBOUF TION H-467S....osssnn 33 3. CHAMBERENVIRONMENTALCONDITIONS... smmssngmm-- 4 MEAN BODYWEIOGFMHALTERASTS vcs 35 5. MEANBODYWEIGHTGAINS OFMALE RATS... I 1 6. SUMMARYOFCLINICAL OBSERVAINTMAILEORNATSS... 3) 7. SUMMARY OF BLOODFLUORINE ANLYSI. A 8 SUMMARYOFHEMAVATLUEOSFLORMOALGE Y RATS. 41 9. SUMMARYOFSERUMAND PLASMACHEMISTRY VALUESFORMALERATS crc 10. SUMMARY OFURINVAALUELSFYORMSALIERASTS... 1 11. MEANFINAL BODYAND ORGANWEIGHTSFROMMALERATS DAY 10 SACRIFICE... a 12. MEANFINAL BODYAND ORGANWEIGHTSFROM MALERATS DAY24 SACRIFICE .............51 13. INCIDENCESOFGROSS OBSERVINAMATLEIRAOTSNDASY 10 SACRIFICE vv... 54 14. INCIDENCESOFGROSSOBSERVATIONS IN MALERATSDAY 24 SACRIFICE vv... 59 ~~ 15. DIANY C10SIACDRIAEFNINDCLECESEIOSN GA RADES OF MICR--OS--CO--PIC OBSEcRrVnATIINMOpANLSEmRATmS ---- 16.DIAYN2C4 ISADCRAEINFNDILCCEESEIOSr N Ge ROAFn MIDCRc OESCOSPe IC OBSERVATIOcNSIrNiMAeLEsRATS --~ ie `Company Sanitized.DossnotcontainTSCA CB SH2-204867:: TTwwooWWeeeekkIInnhballaattioonn TToorxiicciltyySSutuddyyiinnMMaaelReaRsas___ --_ LIST OF FIGURES DuDpuopnoes8s6s8s5. I. Page SCHOEFEXMPOSAURT ESYISTECM oss 15 2. MEANBODY WEIGHTS OFMALERATS... sss sos 3. MEANBLOOD FLUOOFRMAILENRAETScv ------ LIST OF APPENDICES A. DAILY CHAMBER CONCENTRATIONS Page v.19 B. DAILYCHAMBERENVIRONMENTALCONDITIONS... C. INDIVBOIDYDWEUIAGHLTS... wan 2 ------ D.. INDIVIDUALCLINICAL OBSERVATIONSAND MORTALITY E._ INDIANIVMALIBLDOODUFLUAORINLE........ wp RECORDS... 93 -- ~ F. INDIVIDUALANIMALCLINICAL PATHOLOGY DATA.. G. INDIVIDUALANIMALFINAL BODYAND ORGANWEIGHTS... 101 oon 128 H. INDAINIMVALIPATDHOLUOGYADATLA vc SY --~ - `Company Sanitized. Dpes not contain TSCA Ca 2B2768: TToooWWeecekkoIltuatluiioonnTTooxiicctySSutduydyininMMailleeRaRattss - Subse Teco STUDY INFORM SUE) ATION Swmonms/Codes: {SND { H-24678 1 Haskell Number: 24678 Composi pwDruroomns-ss6s8s5 Koon mouse] EN _ Physical ed) Stability: cTohneditteistonssubosfttahnecestaupdpy;eanroedevtiodbeencsetoabflensunadbeirltthyewas observed. Sponsor: EL du Pont de Nemours and Company u`Wsilamington, Delaware 19898 Study Initisted/Completed: August 2, 2002/ (sce report cover page) In-Life nitisted/Completed; August 5, 2002. August 29, 2002 - (Company Saniized. Doss not contain TSCA Cs HAHLT24S678:: TTuuooWWeeeckknInhhaaalattiioonnTTooxniicittyySSodyyninMMaalleRRass DuDurpeomntsseessss : STUDY PERSONNEL Study Director: David P. Kelly, B.S. Management: ArthuJr.O'Neill, B.S. Primary Technician: William E. Ellis, Jr. Clinical Pathologist: Nancy E. Everds, D.V.M. Management: Steven R. Frame, D.V.M., Ph.D. Blood Fluorine Analysis: Vidimir Capk, Ph.D. Management: S. Mark Kennedy, Ph.D. AnatomicMaPnatahgoelmogeinstt:: JStoehvneFn.RH.aFnrsaemne,,DD..V.VM..M,.,PhP.hD..D. Peer Review Anatomic Pathologist: G. Tracy Makovec, D.V.M., Ph.D. Toxicology Report Preparation: Maryanne M. Wilford, B.A. Management: Nancy S. Selzer, M.S. Laboratory Veterinarian: William Singleton, D.V.M., A.C.LAM. --~ -_-- Company Sanitized. Does nox oui + wissl B6H24767:8: TTuwoo:WWoerekknInhhoallatioonnTTooxniiccitySSutuddyyiinnMMualleeRRtatss -- SUMMARY ~~ DuDuoPomnts.e8s65s5 0F.o2u.r2,gororu2p0s mofg/1m5?ma(alceturaaltsmeeaacnh cwoenrceenetxrpaotsioendstwoecroenc0e.n2t2r,at1i.9o,nsanodf H20-2m4g6/7m8')a.erToshoelmtaarsgseted to wmeedrieaenxpaoesreoddynnoasmei-conelqyuifvoarl6enhtoudrisampeetredraoyfftohre aetortoaslolosfraenxgpeodsfurreosm o0v.e9r0 at0t2w.o1-iwme.ekApelriroadt.s A similarly comprised control group of 15 male rats was simultaneously exposed to air only. `wTehreefdierssi1g0nartaetds pfeorr bglroooudp fwleuroeriddeesainganlaytseids fsoarmpstlainndga.rdOtnoxtihceitdyatyesotfintgh.e lTahsteerxepmoasiunrien,gcSollreactstion tohfealnasotveexmpiogshutreu,ribnleoosdpescaimmpelneswawserienictoilalteecdtfeodrfeoarcchlisntiacnadlaarndaltoyxsiecsitfyroramt.eaOcnh sthteanddaayrdfotloxliocwiitnyg wraet,reanadll5roawetds tpoerregcroovuepr wfeorare s1a5c-rdiafyicpeedrfioord.anAattotmhiecenpadtohfoltohgeyreexcaomvienraytpieorni.od,Albllroeomdaainndinugrirnaets wsearmpelseascrwiefirceedc.olOlencltyedthfeorstclainndiacraldtoaxniacliytsyesraftrsowmecraecghisvteanndaanrdantaotxoicmiitcy praatt,haonldogayllesxuarmviinvaitinognr.ats pNeoridoedlse,tearnidoubsodefyfewcetisgwhetrseweorbseesrivmeidlairnicnlitneisctaalnodbsceornvtartoilornasts.durCilinngitchael epxaptohsoulroegyoervraelcuaotvieornys, pinacrlaumdeitnegrsflausorairdeesumletasofuerxepmoesntusr,esthooHw-e2d46n7o8effects in urine, hematology,orblood chemistry ~ tShmealblloaomdooufntrastsofinfltuhoer2in0em(ga/ppmr?oxgirmoautpeloyn 2tepstpmd)a,yssl0i,g3h,tlaynadbo9v(ecobmapcakrreodutno d,tewsterdeayde9tecocntterdoiln fdlautoar)iinnedwicaastidnegtetchteepdrienseantcseoefxptohesetdesatt cthoims pcoouncnednotrraittisomneatfatbeorlithtees2.-wNeoekabroevceo-vebrayckpgerroiuodnd(test ldeavyel2s4)inctohmep0a.r2eadntdotthhee2temstg/damy?2g4rcoounptsrooln tgersotupd.ayN9o(tfhleuolraistnedwayasofdettheecetxepdoasbuorveepebraicokdg).round Weight analysis of the major organs Histological findings were confined showed no effects atributable to the respiratory tract. There to the test substance. were no adverse effects in any aotnhderlaervyanlxuaotfetdesotrgdaanys.10Csoamcpriofuincde-rraetslaattecdonmciecnrtorsatcioopnisc oof2bsearnvadt2io0nms gw/erme. prIensfelnatmminattihoenluinngtshe alutn2gsm,gc/hma?riacnte1riozfe5d rbaytsmianxdedati2n0flmagm/mamtoriny3ceolsf5waittsh.inIsncaatdtdietrieodna,lmvieonliamrallumtoinmailwdassqoubasmeoruvsed Smeattaspalansdiaato2f0thme gmu/cmois?na5lo ini5ngf atthse.ventral floor of the larynx was observed at 2 mg/m in4 of iTnhdeirceatwienrgethneorcevoemrpsoiubinldi-tryeolfactoemdpmoiucnrdo-srceolpaitcedlelseisoinosnsobisnetrhveedluinngteasntddlaayry2n4x.sacrifice rats, w"Thhiecnho-noobtsoexrivceodl-oegfifceacltlyleivmeplo(rtNaOnEtLe)fffeocrtsthaitstrsitbuudtyabilsedteofithneedteasst tshuebshtiagnhceestwceornecednettercatteido.n aTthus --~ for this study, the NOEL is equivalent to the NOEL as defined by the United States - CompanySanilized.Does not contain 1SUA Gal HL24675: Two-Week Inhalation ToxStiudycinMietRayts DuPont 685 --~ 2rsodnefmienendtbaylthPerEoutercotpieoannAgUneinocny ((11999845)),and to th no-observeck-advfroste Tove (NOAEL) NNeOeEdLofnorthreepaebaotevdeifnihnzdliantgisoninetxhpeosruesrpeirwaatsor0y.2trmacgt/omf.rts exposed to H.24678 for 2 weeks, the: _ --_ " `Company Saniized. Does not contaiinn TSCA CBI F2-244667785::TTwwoo-WWeeeekkIInnbhaaljaitoinonTToorxiicciyySStuuddyyiinnMMaalleeRRaattss ______ DDuuPkoonmt8866s85s. --~ INTRODUCTION `eTxhpeospuurrepoisneroafsttohisa2i-rwbeoemke icnohnacleanttiroantisotnusdyofwaHs-2t4o6i7n8veasetriogsaotle. thIenheaflfaetcitosnofisraenpeeaxtpeedcitnehdalraotuitoen osufbhstuamnacne.exIpnoasuprree.viTouhsesdtautdaywaitllthbies ulasbeodratotoprryowviitdhe tihnefosrammaeticoonmfpoorusnadfe,htahned4l-ihnoguorf the test aafptperroexxipmoastuerelett0ha2l3comngce/nmt.ra"tioInmm(eAdLiCa)teilnynporsieo-rotnolytheexpproesseedntrasttsudwya,sa5r7anmggef/imn;dinnog erxatpserdiiemdent 6wadsaycso,nwdiutchtiendainn8g-rdoauypspoerfiroadt,steoxapomseeadnncoosnec-eonntlryatfioornaopfpraopxpirmoaxtiemlayte5l2y-108-m6 hgou/rosfm/tdha?ey ftoerst cwiotmhpoouutnedx.poNsuores,igtnhiefiscaanmtecrlaitnsicwaelrseigenxspoofsetdoxfiocrit5y whoeurresotbosearmveeda.n Fcoonlcleonwtirnagtiaon3-odfay period caopnpcreonxtirmaattieolnyo4f469mgm/gm/?m?foolfloHw-e2d46b7y8.a fiFniavle4ohfo6urraatsnddi2e0d mwiitnhuitne2exdpaoyssuorfetthoealamsetaenxposure. Cdliisncihcaarlges,iginrrseogfultaorxirceistpyiroabtisoenr,vaenddimlemtehdairagyt.elyThfeoldlaoywifnoglltohweilnagsttehexploasstureexpionsculruedeldu:nrgendoniassealand severe weight loss were also observed. foBrastehdeo2n-wtheeekabionvhaelaitnifoonrmsattuidoyn,deesxcproisbuerdeicnotnhciesnrterpaotrti.ons of 0.2, 2, and 20 mg/m? were chosen --~ STUDY DESIGN F2,0or ur2g0romugp/smo'.f 15Almlarlaetsrawtesreeaecxhpwoesreed enxopseo-soendltyofcoorn6cehnoturrastipoenrsdoafyHf-o2r4a6t7o8tatlaorgfe9teedxp1o0.s0u,re0.s2., Tthheelafisrtstex1p0osruatrse,pecrolglreocutiponwoefraendeosviegrnnaitgehdtfuorrisnteasndpaercdimteonciwtaystiensittiinagt.edIfmomrecdaicahteralt.y fOonlltohweing dstaayndfaorldlotwoixnigcitthyeralta,staenxdpo5surrates,pbelrogordosuapmpwleerse wsaecrreifciocleldecftoerdafnoartcolmiincicpalatahnoalloygsyesexfarmoimnaetaicohn. Apelrliroed,masitnainndgarrdattsoxwiecriteyarlaltsowweedretofraescteodveorvefronriagh1t5,-bdlaoyopderainodd.urAintetshaemepnldesofwtehreerceoclolveecrtye.d for calnianticoamlicanpaaltyhseoslofgryoemxacmaicnhartaito,na.nd all surviving standard toxicity ras were sacrificed for `toTthaelrfelmuaoirinniengan$alryastisspwearsgrcooullpewcteerdefdreosmigenaacthedraftodrurtoitnagltfhleuoreixnpeoasnuarleyspihsasseamopnlintegs.t dBalysoo0d, f3,or asunbds9e,quaenndtldyurainnaglytzheedrefcorovfelruyorpiener,ioadndonthteesrtedmaayisni1n4gasnadmp24l.esSweelercetesdavbeldoofdorspaomspsliebslewfeurteu.re analysis. At the end of the recovery period, all rats were sacrificed without further examination. _ eAxllporsautsreweperreiowde.igGhreoduapncdliinnidciavlisdiuganlslywoebrseerovbesderfvoerdcldiunriicnalg seiagcnhseoxfptoosxuircei.tyItnhradoduigthioount, tthhee Company Sanitizod. Doesnotua 15UA ok S 24675: Tuo-Week Inhalae tionTTooicrityySSwtuddyyiinn MMaalleeRRao atss _ n DpuPuoonmt.e8s6s85. ~~ aalcehrtienxgproessupreo,nsreattsowaenreaucdhiteocrkyedstfiomrultuhse awlaesrtcinhgecrkeespdobnesfeortoe aanndaudduirtionrgyesatcihmuelxupsopsruiroer.toAfter ~ rreetmuovmaeld ftorotmhirresctargaeisn.ersSuarnvdiwveirnegorbastserwevreed of toxicity throughout the recovery period. wfeorigclhiendicaalndsiignndsiviimdmueadlilyatoeblsyearfvteerd they wero. for clinical signs MATERIALS AND METHODS A. TestSubstance Thetestsubstance,H-24678, was supplied by the sponsor Purity was o'be stable throughout the exposure phaseofthe study; no evidenceofesitnsstuabbisltiatynwceawsasobesxeprevcetde.d B. Animals RAalteoitaglh,ofNo6r3tmhaClaeroClrinla:.CDT(hSeDr)atIsGwSerBeRarpaptrsowxaismarteecleyiv6ewdeferkosm oClhdarolnesthReidvaeyroLfaabrorriavtaolries, Inc., Rats have historically been used in safety evaluation studies for inhalation toxicity testing. The ~ eCxrtle:nCsiDv*e(SeDxp)eIrGiSenBceRwriatthwathsessetlreacinteadt based on consistently Haskell Laboratory. acceptable health status and on C. Animal Husbandry 1. Temporary Animal Idenification and Quarantine qUupaornanatrirnievdal,foera7chdaraytswparisorasositgensetdinaittiaetmipoon.rarDyu,r1i-ngtot2h-edqiugaitraindteintniefipceartiioodnrnautmsbweerr.e wRaetisghweedre and observed 3 times for clinical signsofdisease. 2 Housing Rats were housed singly in stainless steel, wire-mesh cages suspended above cage boards; 3. Animal Room Environment 2EA3nnviimra1olnCmreoanontdmaslarwecelornadteiimtviaeoihnnustmaoiifdnitehtdeyorrnoanoagmtesimowefre5-rc0eon+ttarr1og0le%lte.edd,Etox1c2bu-erhsowiuiortnhlisingohuattt/se1im2d-peheoorufarttudhraeesrekrarcnaycnglgeee.osfwere of insufficient magnitude and/or duration to have adversely affected the validity of the study. --~ - Lompany Sanitzed. Doss notcontain TSCA BL24678: Two-Week Iohalation Tricity Study inMaleRats DuPont8685 --~ 4. Animal Selection and Permanent Identification SRioattohsartwoemretehaednievnbidododeyfd tnwheteiogqghutrasoruafopnstiewnaietcphhetrghireoodua,pidrwaotesfrweaecsroiemmipalusatsre.irginRzeaedtds0, s4gtrratoiutipeds, oaf n15dmaolerra:tsperaocghr.am, and weighed between 231 and 276 grams at the tart of the expwoesruereaspproximately secs oor 3`-Udpiognitgirdoeunptiinfgi,cactiaocnhnruatmwbaesr awsassigtnaetdtoaoeudnioqnuteo 6-digit the tail aonfiemaaclhnruamtber. Following grouping, a dRiastcsarthdaetdwweirtehonuottaansastiogmneidc tpaathtoelsotggyroevuapluwaetrioen.sacrificed by carbon dioxide asphyxiation and 5. Feed and Water CpxeecrrteiiopfdtiseddpurRirooirdngetonetxnpeLocasrbuoDrpiseey,.ttap50w0at2ewrawsaasvaaivlaaibllbelaeaddlilbiistutma`.excPepMtIdurNiuntgietxopnosnuerremasnidonfaalst,inLgLC 6. Health Monitoring Program to`hAlsolssoepwetichniagftipwerodouiclneddthubereeHesaxsapkreeecltpleeLdraftbooorrimametpdoarpceytraitnohideimscacalilelhnyetiatfloitcehniasnnutdergeeritnthvyaitrocofnotmnhetnatmailnamnotniltevoerlisncgsprpogerarm, the. study TM Wanadteorthsearmcpolnetsamarienaanntaslyzed for total bacterial counts, and the `presenceofcoliforms, lead, + Feed samples are analyzed for total bacteria, spore, and fungal counts, bSaymtphleecsagferwoamshferress.hly washed cages and cage racks are analyzed to ensure adequate sanitation sTCpeoerictfiiffeiimeeeddnhatensiamvaaynlmdefnteaeolds0i,saeufsxleacdte,oexdgions,aarcthaelndoirmeiadnaxbtiyedmtuhheymdmrcaooncnucafernbatocrntasut,rioeantsoomfekeetyscpoenctifaimeidnamnuttsi,tiionncalluding Wproeusledncneootfbetheexspeeccotnetdatmoiniamnptasctbetlheowinttehgerimtayxoifmtuhemsctoudnyc.entrantdioonrsgtaantoepdhobsyphthaetemsa.nufTahceturer alifahfbeeocratanetdiomrtayhleanhvieaamlliadtlihtvyaentoedfrietnnhaevrisirtaoun.ndym.eEnvtaalluamtoinointoofritnhgepsrdoagtraaimdisnaodtmiinndiisctaetreead mbyctohendatotneneditnhgat --~ -Y Company Saniized. Does notcoriain TSCA CBI H24675: Te wo-Wei ek Inhn alationTTooxricciityySSutdudyyiinnMMelleeRRaattss ~~ D. (IFnihgaulraeti1o)n Exposure System DuDupPoomns8e6ss5 1. Aunosphere Generation `SCmyhosadtemelbme2sr2NSaeytburmlioinszgpeehreI.rnefTsuhsweieotnreesPtugsemunpbe.srtaatFnielcdteebrwyeadns,ehbmuielgtihez-rapetrdieosinsnuoorfettahhier,ntmeesbetutlseiurzbeesdrtaiwnnitctoehtiahneHanaierrbvwuailrtidhzaeASrppbprayaryaaitnusg aBtrmoooskpshmeoredetlhr5o8u7g8h MaacsycslFonleo,wtChornoturgohllaergsl,asastfolmoiwz-esdpltihteert,esatnsdubisnttaontcheeaenxdpocsaurrrieecdhtahmebreers.ultTihneg tfhleowexsppolistutrere dcihvaemrbteedr.actDoisloultitoontahier,hmoeotdereexdhaiunstto ttoherecdhuacmebtehrebaymoauBnrtoookfstemstodmeatler5i8a7l8reMaacshsing TFhleowinCfounstiroonllperu,mhpelapneddmtaosesvefnlloyw dciosnttrrioblulteersthweetreestcsountbrsotlalnecde atnhdromuognhiotuotrtehdebeyxptohseuCraemcihlaember. cIonnhcaleanttiroantiToonxiwcaoslaocgcyoAmuptloimsahetdedbyDavtaarySiynsgttehme t(eCsItTsAuDbSs)t.ancFeifneeecdonrattreoltootfhtehenecbuhlaimzebre.r fTeusmteahtomoods.pheres were exhausted through an MSA filer cartridge prior to discharge into the 2. Chamber Construction and Design ~ iAnltleernxaplovsuorleumcehaomfb1e5r0s Lwe.rAe pcoonlsytcraurcbtoendaotfe sbtaafifnlleeasstshteeeclhaanmdbegrlasisnl(etNpYrUomsottyleed) uwniithfoarmnominal chamber distribution of the test atmosphere. 3. Exposure Mode cDounriicnalg nexopsoespuireec,esa.niTmhalesrweterraeiniendrisvwideuraelliynsreerstterdaiinnetdo ianppoelryfmoertahtyedlmsettahianlcersyslsatteeelfaccyelpilnadteerswhwiitchh dcwahayassmbafetorar.cahpeBpderfotoxoritemhatetheeelxsyptoa1rst5uromefintcuhhteaeemsxbpeeoarscuhsrodetaphyhtatosteha,eccanlnoiismmeaatolefs etwhaeecrhaenapinlmiaamclaesldtpoirntorhteersurtderseatidrnaeiirnnsteorost,nhe2 esxeppoarsautree E. Characterization of Chamber Atmosphere 1 Test Substance Sampling and Analysis aTphperoaxtimmoastpehleyri6c0c-omnicneuntteraitniteornvaolfsHd-u2r4i6ng78cawcahsedxpeotseurrmei.nedThbeycgornatvriomletcrhiacmabnearlywsaiss astampled zoonnee odfurtihnegatnhiemsatlusdyt.hrKoungohwan25vomlummefsiltoefcr hcaasmsebtetertahattmocsopnhtaeirneewdearpered-rwaewinghferdomGtehlembarneagtlhaisnsg cTfoihbneecrefni(tlTtreyarptweieoAin/gshEbt)assfiweledterroe.naTtuhhteeomdfaiitflitfecerarslewlncyeerteirnawnpesrfieeg-rhraeendddtoponoCsaItC-TsaAahDmnSpl,miowndgheilfcilhCte-cr3awl0eciougrlhaCtt-es3dd1tihvMeiidccerhdoabmbabyleatrnhcee. -YYY Company Sanilized. Doesnot contain TSCACsi LHL-2244667788::TTwwooWWeeeekk InnbhaallaatioonnTToorciclityySStuuddyyiinn MMalleeRRaiass__ DuDPuoPmoens8s6s8s5 -- svaomlpulmeeowfercehcaomnbterrolaletdmoasnpdhererceosradmepdlbeyd.CIGTraAvDiSm.etric sample start- and stop-times for cach 2. Panicle Size Determination `aSnadmgpleeosmettordiectsetramnidnaerdthdeevaieartoisoonl)pwaretrieclteaskiezne odniscteripbeurtiwoene(kmaisnsthmee2diaannd a2e0romdgy/nma?micchadmibaemertser witha Sierra Series 210 Cyclone Preseparator/Cascade Impactor and Sierra Series 110 Constant Flow Air Sampler. On the last exposure day of the study, the aerosol particle size in aslelns3ocrshaamnbderalslwowass mmeeaassuurreemdeinntdoufplaicsamtaellwimtahsas QofCaMcroIsmopla.ctTohre."Q' CThMesQenCsiMtivuisteyswpaisenzeo-ecdreysdttaol measure the particle size in the 0.2 mg/m? test chamber. 3. Environmental Monitoring `Cpherahmobuerraanidrfwleorwes wmoenrietsoerteadtctohnetbineuaglliy wniontfhieanaccaghliebrxaptoesdurBerotookaschmioedveelat58le7a8stMa12ssaiFrlcohwanges CtoynpteroJlTlehre.rmCohcaomupbleerTtheemrpemroamteutreer.wasChtaarmgbeetredraetla2t3iv+e h2umCidaintdywwaassmteaargseutreeddatwi5t0h an1O0m%eagnad Awiarsflmoewa,stuermepderwaittuhreJ,uamnodmroedlaetlivPeThLu0mi0dwietty-wbuelrbe/dmroyn-ibtuolrbedrecsoinsttianncuealtleympweitrhattuhreeCdIetTecAtDorSs.and rnoetcomredaesduarted15i-nmionnuetoerimntoerrevaclshadmubreinrgs eoavcehr epxeproisoudrse.of O15nm3inoucctaessiotonsa,ppthreoxriemlaattievleyh2umhioduirtsy dwuaes to sensor problems. Based on the overall stability of the relative humidity measurements over the ~ dtourhaatvieonaonfetfhfeecsttoudnyt,htehsetiundaybioluittycotomem.eaCshuarembheurmiodxiytgyeonvecrontcheenstera3tpieonriwodass wtaarsgcetoendsitdoebreedatnot least 19%. Chamber oxygen concentration Oxygen Analyzer and was recorded 3 times was measured with a Biosystems during cach exposure. model 3100R F. Body Weights and Clinical Observations oDbusreirnvgedthfeoerxcploinsiucrael psihgansseooffttihecisttuydyb,efaollreraatnsdweafrteerweeaicghheedxpoonsuerex.posGurroeudpayclsinaincdalindividually orbesseprovnasteitoonsanwearuedimtaordyesdtuirmiulnugsepxrpioosrurteos.eacIhn eaxdpdoitsiuorne,,raaptsprwoexriemactheelcykeedvefroyr2anhoaulrerstdinugring cach eaxnpdoisnudriev,idaunadlalfyteorbseearcvhedextpwoiscuerep.erDwuereik.ng the recovery period, al remaining rats were weighed G. Blood Fluorine Analysis Bafltoeordnofoonrstootfaltefstludoaryisne0,an3alaynsdes9.waBslocooldlewcatsedal(0s.5o ttaoke1nmdLu)rifngrotmhe5rreactosvpeerrygpreoruipodoonnthteest dblaoyosd1w4aasndan2a4l.yzTehdefobrlofloudosrianmeplinesrawtsereexpforsoezedntfoo2r0tomtagl/flmuoorfinHe-a2n4a6l7ys8isanads nseaemdpelde.d Whole _ immediately afier exposure on test days 0, 3, and 9, and after a 15-day recovery period (test - `Company Sanitized. Does notcontain TSCA GBI 2244607788::TTwwoo-WWeeeskkIInnbhaalluaitoionnTTooniicciltyySSutuddyy iinnMMaalelReatRsats___ DuDubpoomns.8s6s8s5. ~ dexapyos2u4)r.e. WhUonalneabllyozoeddfsraommpltehse rweemraeisntionrgedgrfooruppsoswsaisblaenfaultyuzreedflounortienstedaanayl9y,sitshe last day of `The total fluorine content of the blood samples was determined using aWickbold torch c`wohmobluesbtliooondmweatshoddecfoomlploowseeddboyr avnoallaytsiilsizweidtihn athfeluporreisdeenicoenosfelweecttiovxeyegleenctarnoddes.w"epTthethlrioquugihd an oaxqyu-ehoyudsraobgseonrbfilnagmesoilnutaicolnoasnedd qaunaarltyzzeadppuasriantgusa.fTluhoericdoemibounssteiloenctpirvoedeulcetcstrwoeder.e collected in an H. Clinical Pathology Evaluation Aappclrionxiicmalatpealtyho1l0odgayyesvaalfuteartiionnitwiaatsiocnoonfdtuhcetestduodyn.aTlhreatdsadyesbiegfnoarteecdoflolrecsttiaonndoarfdstaomxpilceitsyftoersttihneg cflaisntiecdalovpeartnhioglhotgy(aepvparlouxaitmioant,eltyhe1a6nhiomuarlss)waenrdeuprlianceewdaisn cmoeltlaebctoeldisfmrocmageeasc.hTahneimsael.aniBmlaolosdwere ssianmupsleosf cfaorchheamnaitmaollowghyilaendthcelianniicmalalchweamsisutnrdyemrelaisghutrecmarebnotnsdwieorxeidceolalneecsttehdesfirao.mBtlhoeoodrbsitaamlples fwohrilfelutohreidaenianmaallyswiasswuenrdeecrocllaercbtoend daitosxaicdreifainceesfthreosmiat.heAadbddiotmioinnaall bvleonoadccaovllaoecfteedacfhroamnitmhael dviesncaarcdaevdawwiatshopultacaenadliynsiassbeercuamusteubfeu,rtphreorcteessstsedwetoresenroutmr,eaqnuidrfedrotzoensuaptp-o8r0tCe.xpeSreimreunmtawlas fmianrdirnogws.smBeoanres mwearreroswtaisnmeedarwsitwheWrreigphrtep'asrsetdaiant asancdricfoivceerfslriopmpealdl,sbuurtviavnialnygsainsiwmaalss.notBone ~ necessary to support experimental findings. 1 Hematology Blood samples were evaluated for quality by visual examination prior to analysis. Complete banlaoloydzceoruonrtsd,etienrcmluidniendgfrreotimcumlioccryotsesc,opwiecreevdaeltueatrimoinneodf othneabBlaoyodersmeAadrv.iaWr1i2g0hth-esmtaationleodgbylood asnmedaervsalfuraotmioanlol facneilmlaullsarwemroerpehxoalmogiyn.ed Bmliocroodscsompeiacrasl,lsytafoirnecdonwfiitrhmnateiwonmeotfhayulteonmeabtleude,rewseulrtes epxraempianraetdiforno.m cach animal undergoing a hematology evaluation but were not needed for `The following hematology parameters were determined: red blood cell count hemoglobin platelet count white blood cell count hematocrit mean corpuscular volume differential white blood cell count microscopic blood smear examination mean corpuscular hemoglobin `mean corpuscular hemoglobin concentration red cell distribution width absolute reticulocyte count --~ --_-- CompanySenilized.Doss ot conan SGA Gl -- LS 2L4246677u 88::TTwd uooWWeey eekkIInnhi haallaattiin oonnTTooirM iccltyy Sa tudy il n MaleeRatsRats___DuDp_ uoPnoen8s_ 6e8s5s 2. Clinical Chemistry S71e7ruclmincilcianliccahlecmhiesmtirsytarnyaplyazrearm.etPelrsaswmearefldueotriedremsinweedreondeatReromcihneedDiuasginnogstaipchsil(2BMpCH)/mHeittearchaind a fluoride-selective electrode. "The following clinical chemistry parameters were determined: aspartate aminotransferase alanine aminotransferase: sorbitol dehydrogenase alkaline phosphatase. total bilirubin urea nitrogen creatinine cholesterol triglycerides glucose otal protein albumin globulin calcium inorganic phosphorus sodium potassium chloride fluoride 3. Urinalysis --~ Urine volume was measured. fluoride-selective electrode. Urine fluorides were determined usinagphi 12 pH meter and a "The following urinalysis parameters were determined: volume fluoride" 4. Recovery Cflliunoirciadle wpeatrheopleogryfoervmaelduaattiothneiencnldoudfitnhgehermeactoovleorgyyp,ercliiondic(aelscthdeamyis2t4r)y,acacnodrpdilnagsmtao tahnedmuertinheods detailed above. 1 Anatomic Pathology Evaluation 6Mahloeurrsa/tesxwpoesruereesx)p.osTeedntoantihmeatlesstpseurbgsrtoauncpewfeorre2ewxepeoskesd(ttootatlheoffo9lleoxwpionsgu:reasirfoornly (Control GExrpoouspurI)eaGnrdotuopHV-)2,4a6n7d8a2t0 0m.g2/mmg?/(mH?ig(hLoEwxpEoxspuorseuGreroGurpouVIpI)I.D),Fi2vme ga/nmim*a(lIsntpeerrmgerdoiautpe were sacrificed and necropsied following the last exposure (test day 10 sacrifice). Another 5 animals --~ * FFlluuoorriiddee ddeeteesrmmiinnaattiioonn wwaassaannaallyyzzeedd fornoEmDuTriAnepwliatshmaEDTA added - CompanySanitized.Does not canta SCA C71 HZL24T67E8: TTowoo-WWeeeekkIIonhhaaalattiioonnTToonxiiccitySSutuddyyiinnMMaaleleRaRtsats__ DDuuPpoonets8e6s85s ~~ p(teerstgdraouyp2w4esraecriaflilcoe)w.ed to recover and were sacrificed and necropsied on the 15 day of recovery Rats were euthanatizedbycarbon were performoend all ats. dioxide anesthesia and exsanguination. Gross examinations "The following tissues were collected from the standard toxicity study rats Digestive liver System Respiratory lungs. System~~ Nervous System brain (3 cross sections) esophagus stomach trachea nose (4 cross sections) sppeirniaplhceroarldn(e3rvcero(ssscisaetcitc)ions) duodenum pharyn/larynx jejunum ileum Cardiovascular System Musculoskeletal System stemum cecum heart colon Reproductive System praencctruemas. HespmlaeetnopoieticSystem etepsitdeisdymides Urinary System thymus prostate mesenteric lymph node~ seminal vesicles Kidneys bone marrow --_ urinary bladder Miscellaneous Endocrine System thyroid gland eyes (including opic nerve) 105s observations parathyroid glands adrenal glands a Bone marrow was collected with the sernu, `bTohdeyliwveeir,ghktidannedyso,rgluanngsw,eibgrahitnb,raanidn tweesitgeshtwerarteiowsewiegrheedcaaltcunleactreodp.syF,inaanldboordgyanwewiegighhtts/final determined just prior to necropsy were used in the assessment of organ weight changes. Gaprporsosprlieastieon(se.wgh.ifclhuiwdearcecudmiualgantoisoend,artunffelcerdopfusry,amnidssfionrgwahniacthommiiccrpoasrctos)piwceerxeagmeinneartailolyn nwoats not coosltleeocatretdh.ritiGsr,opsosdloedseiornmsaifotriw,hcihcrhonaicmidcerromsactiotpiiscodfiatghenotsaiils, wuroiunladrynocatblceulaid,daintdivdeef(co.rgm.ity of the teeth, toe, tal, or pinna) were saved but were generally not processed for microscopic evaluation. T1e0st%esn,euetpriadlibduyfmfiedreesd,faonrdmaelyiens. wPerroecefsisxeedd itnisBsouuesinw'esrseoleumtiboen.ddeAldliontphaerraftfiisns,uecsutwearteafnioxmeidnianl ~~ tmihcircoksnceospsicoalfSlym.icrometers, stained with hematoxylin and eosin (H&E), and examined ee Compae ny Sanilized. Does nos conan TSCA GBI L2244667788::TTuuooWWeeeekkIInnhhaallaattiioonnTTooxxicciityySSutuddyyiin MMalelReaRtsas___ DuDupPoomntss86s8s5. ~~ wAlelrecoplrloeccetesdsetdisasnudesrfercoeimvtehdeatefsutlldhaiyst1o0pastahcorilfoigciecarlatesxianmitnheatcioonnt.rolLiavnedr,hkiigdhneeyxsp,osluunrgesg,roups `exhpaorsyunrse/agrryonusp,s t(eIslteas nadndV)noasned ffrroomm tthheetteessttddaayy 1204ssaaccrriiffiicceersattasnidnarthdetloxoiwciatnydraitnstienrmtehdeicaotnetrol and high exposure groups (1 and VII) were processed and examined microscopically. `pTahtehokleoygtyottahbelepsaatnhdolaopgpyenldesiicoens.grading system use in this study can be found within the J. Statistical Analyses Significance was judged at p < 0.05. PEaxrpaomseutreerConcenration Preliminary Test psigrnieficlanit mitenstaisrnoyt |sIifpgrniefliicmainntary ts EnDviruonamental Data Nore Descriptive statistics (e.g, mean, standard deviation) [Blood FivorineAnalysis [None [SSweqdueenntisaTl pepslitca"tion" of - BS ody WeiR ght Test for ack of trend |heereJonckhecre Terpstra |Pparierlwiimsienacroymepsatrsisfoorn Organ Weight Shapiro | ODvnuenn-nw'acsy aemfsloylsliosvoefwith ||a EKroulslkoagle-dWwaitlhsDtsots Tcidenceof Clinical o> Clinical Pathology" Tevens's est for homogeneity" ando.o. Ovanreier-awncaey afnoalllyowseiodsfw3i;th || Kfroulslkoawle-dWwailtlhisDuensnt'oAso ape I Donne test en a Pasiigrnwifiisceancto.mparisons and associated preliminary fests were nly conducted ithe tet for lacofend was IwIfahtsheeusiSenhdc.aipdiIerfnotc-heWeiwSlahkaspneiosrto-swiWagsniinkfoicteassntitg,wnbiaufsitcsaaingstniigbfnuiitcfaiLnctae,ntKvrJuaesckknaoeflssf-tWiwataloslcissciugtrneietfdi,wcaatnshte,fnolFrilosobhwueesrdt'sbvyEexrDsauicnotnnoe'fsatDesutwnitnhea est oWBonhnehfanelfrratonhnieindrcieovcnioedrcudtaeildoonvbaswlueaers.vastFeoidro.enxwaamsprleec,oridbeidlaisrbbieninwgalsesrs ethpanoractere<t0da.in1,va0l.u0e5, wcaalscuulsaetdiofnosr waenryecaplecrufloartmioends performed with ha bilirubin dota. ~~ -_-- a `Company Sanilized. Uoes not contain TSCA CBI LLH2:244067788::TTwwooWWeeeekkIIonbhaallautiioonnTTooxriicciittyySStuuddyyiinnMMaaelReatRs:es__ --_ RESULTS AND DISCUSSION DDuupPoomnteg8e6s85s In-Life Animal Measurements A. CCohnadmibtieornsAtmosphere Concentrations of H-24678 and Chamber Environmental (Tables 1-3, Appendices A-B) ``eTxhpeomseuraens carhealmobceartecdonicneTnatbrlaetison1saonfdH2-,2r4es6p7e8ctaivnedlyc.haTmhbeermeeannv,iraonnamlyetnitcaalllcyodndeitteiromnisneddu,rianegrotshoel c2,onacnednt2r0atmigo/nms?f,ortrehsepe9cteivxeploys.urTeasrgweetreed0c.o2n2c,en1t.r9a-atnidon2s0amreg/usme?dftohrrtoaurggehtouctontcheinstrreapotrito.nsoNfo0.2, aoefrtohseolH-w2a4s6d7e8teacetreodsoiln mtheeascounrterdolinchtahmebteerst.atTmhoespmhaesrsesmerdainagnedafcrroomdy0n.a9m0itc0e2q.u1ivyaml,ent diameter `hTuhmeidcihtaimesbefrorotxhyegcehnacmobnecresntrraantgioendsfwreorme32619to% 6in7%al,l cahnadmtbheerdsa.ilTyhmeedaaniltyemmpeearnatruerleastirvaenged --_ wferroem s1l9igthotl2y5oCu.t oAflrtahnogueg,hthiensseodmeevicaatsieosnsthweerreelamtiinvoerhuamniddiwteyreannodtteexmppeecratteudrteomaeffaescutrtehmeesnttusdy outcome. B. B(ToadbyleWse4i-g6h,tFsigaunrde 2C,lAinpipceanldOibcseesrCv-aDt)ions `diTfhfeemreenatnfrboomdythwoesieghotfsthoef cmoanlteroalnrdatfsedmuarliengrattsheeoxvpeorsaelld ctoouHr-s2e4o6f7t8hewestruedyn.otTshteatriestwicaasllay swleirgehtnloytdestparteisstsiecdalwleyidgihfftergeanitnfornomtestthdosaeyo7fitnhethceon2t0romlsg./m? group but the group body weights Nexapsoasluaren.d oTchuilsarisdaisfcrheaqrugeenstwoebsreerovbatsieornveidn iinnhmaalantyiornatsst,uidnicesluwdhiengrecornattrsaolrse, iemxmpeodsieadteinly afer restrainers, and is not considered to be deleterious. During the study test treatment. there were no notable clinical observations that may have been related to the --~ - Company Sanilized. Donotecomsa 15GACBI DH22466778:TTwwooWWeecekkIInnhhaallaattiioonnTTooxriicciittyySSttuuddyyiinn MMaalelReaRtsats___ ~~ Blood Fluorine Analysis DuDPuoPmoens8s6s8s5s A. Blood Fluorine Analysis (Table 7, Appendix E) `1S.m3apllpammoinuncotnstrooflfslautortienste d(aaypp9r)o,xwiemraetedleyte2cptepdm)i,n stlhieghbtlloyoadboofvreatbsaicnkgthreou2n0dm(gap/pmrogxrimoautpeolny test days 0, 3, compound or and 9 (compared to its metabolites. No atebsotvdea-yba9cckognrtoruonlddaftlau)oriinndeiwcaatsindgettheectperdeisnenrcatesoeftxhpoesetedstat this cgornocuepn.trNaotifolnuaofrtienretwhaes2-dewteeeckterdecaobvoevreybpaecrkiogdro(utensdt dleavyel2s4)inctohmep0a.r2eadntdotthhee2temstgd/amy?2g4rocuopnstroonl test day 9 the last day of the exposure period). Clinical Pathology Evaluation A. Hematology (Table 8, Appendix F) ~ `aTthsereexpwoesreedntootHr-e2at4m6e7n8t.-related or statistically significant changes in hematologic parameters in B. C(lTianbilcea9l,CAhpepmeinsdtirxyF) `HT-h2e4r6e78w.ereTnhoe afdovlelrosweincghastnagteisstiicnalcllyinsiicganlifcihceamnitsatnrdy/poarrtarmeeattemresnti-nremlaalteedrcathsaenxgpeoisnemdetaon clinical cchoemmpiosutnrdy:parameters were considered to be non-adverse or not related to exposure to the fest + tUrreeaatmneinttr,ogaenndwatasthmeiennidmaolflythdeercerceoavseerdyipnemrailodes(teexstpodsayesd t1o02a0ndm2g4/).mAatftberot1h0tdiamyes-poofints, oufretahonsietriongeonthceorncgernoturpast,iaonnsd isnimmiallaerstoexhipsotsoeridcatlo c2o0ntmrgo/lmv?aluweesr.e gTehneerrealwleyrewinthoianlttehreartiaonngsein oalttheerratrieolnasteidncrleinnailcahlipsatotphaotlhooglyogpya.raTmheetreerfsor(eu,ritnheisvoclhuamneg,ecwraeastiunnilniek,elpyhotsopbheorruesl)at,eadntdo no atrnedattmheunst.waRsecgaorndsliedsesr,edminnoin-maadlvleyrsdee.creased urea nitrogen has no toxicologic significance, + 1A0lbduomsei-nrewlaastimonisnhiimpaltolythiencrreesapsoendsei,n smoaltheissecxhpaonsgeedwtao s c0o.2nmsigd/ermedontotebset udnaryel1a0.tedThtoere was treatment. --~ ee -- "Company Sanilized. Does not contain TSCA CBI H24678: Two Weck Inhalation Toit Sady in Mile Ras ~ C. (UTraibnleeV1o0,luApmpeendix F) There were notreatment.related changes in urine volume. Dupont 3685 D. Plasma and Urine Fluoride Exposure to H-24678 did not result in changes in plasma or urine fluoride. E. Conclusions | cIlninciocnacllupsaitohno,loegxypopsaurraemeotfermsa.leThrearsef(o0r2e,0 umngd/emr?thHe-2co4n6d7i8tidoindsnoofttrheissuslttuidnyaadnvderfsoercthhaencgleinsicianl | pathology H-24678, parameters the highest emxepaossuurreed,intthheisnos-tauddvye.rse-<ffect level for male rats was 20 mg/m? Anatomic Pathology Evaluation A. Mortality ~ (Tables 15-16) There were no compound-related deaths in this study. B. Organ Weights (Tables 11-12, Appendix G) H"T-h2e4r6e7w8e.reThneorceowmeproeunndo-setlaatitsetidcaolrlgyasnigwneiifigchatntefofregcatsn awteciigthhtercshaacnrgifeisceatinthaentiemsatldsaeyx1p0osed fo tseasctridfiacye.24Hsiagchreifrimceewaansabasttorliubtueteldivteorhwiegihgehrtftinhaalnbcoondtyrowleiignhhtiginh tehxaptogsruoruep.group ras from the C. G(FraobslsesOb1s3-e1r4v,atAipopnesndix H) o`Tbhseerrevweedrien n1ohcioghmpeoxupnods-urreelaattedfrgormostsheobtseestrvdaatyio2n4ssiancrtihfiisces.tudTyh.isDoibssceorlvoraattiioonnwoafstnhoetlung was. | tcohnssiradt.ereOdth0erbgercoossmpoobusenrdv-arteiaontsedocbceucrauesdeitnhleroewwianscindoenccoersraensdpownedriengrmaincdroomslcyopdiisctrliebsuitoendin across control and treatment groups. --_ oH `Gompany Sanilized. Doesnotcontain TSCA UB HL-22406778:TTwwooWWeeeekkIInnhhaallaattiioonnTTooxriiccittyySSutuddyy iinnMMalaelReatRsas___ --_ DDuuPpoonmtes86s8s5 CONCLUSIONS 0F.o2u,r2,gr0oru2p0s mofg/1m5?ma(alceturaaltsmeeaacnh cwoenrceenetxrpaotsioendstwoecroenc0e.n2t2r,at1i.9o,nsanodf2H0-2m4g6/m7?8).aerToshoel mtaarsgseted to ``wmeerdeiaenxpaoesreoddynnoasmei-conelqyuifvoarl6enhtoudrisampeetrerdaoyftfhoer aaetrotoaslolosfr9aenxgpeodsfurroems o0v.e9r01a022-.w1egemk.perAiloldr.asA similarly comprised control group of 15 male rats was simultaneously exposedto air only. Npeoridoedlse,taernidoubsoedfyfewcetisgwhetrsewoebrseesrivmeidlairnicnlitneisctaalnodbsceornvtartoilornasts.durCilningitchael epxaptohsoulroegyoervraelcuoavtieornys, including fluoride measurements, `parameters as a result of exposure showed no effects to H-24678. in urine, hematology, or blood chemistry `tShmeabllloaomdooufntrastsofinfltuhoeri2n0em(ga/ppmr?ogxriomuatpeolny 2tepstpmd)a,yssl0i,g3h,tlaynadbo9v(ecobamcpkagrreodutnod,tewsterdeayde9teccotnetrdoiln dfaltuao)riinnedwicaastidnegtetchteepdriensernatcseeoxfptohseedtesatt cthoimspcoouncnedntorratitisonmeatfatbeorlitthees2.-wNeoekabroevceo-vebrayckpgerroiuodnd(test dleavyel2s4)inctohmep0a.r2eadntdotthhee2temstgd/amy?2g4rocuopnstroonl gtersotudp.ayN9o(tfhleuolraistnedawyasofdettheecetxepdoasbuorveepberaicokdg).round ~ H`iWsetioglhotgaincaallyfsiinsdoifngtshewemraejocronofrignaendstsohtohweerdesnpoireaftfoercytstraatctt.ribTuhtearbleewteortehenotesatdvseubrssteanecfef.ects in any oatnhderlaervyanlxuaotfetdesotrgdaanys.10sCaocmrpiofuinced-rrateslaattecodnmciecnrtroastcioopniscofobs2earvnadt2io0nmsgw/emr'e. prIensfelnatmminattihoenluinngtshe alu2ngsm,gc/hma?raicnte1riozfe5d abtysmainxdedati2n0flmagm/mamt?oriny3ceolfls5wriatths.inIsncaadtdtietrieodna,lvmeionliamrallutmoinmailwdassqoubasmeoruvsed `metaplasia of the mucosa 5 tats and at 20 mg/m? in lining 5of the ras. ventral floor of the larynx was observed at 2 mg/m' in 4 of `iTnhdeirceatwienrgethneorcevoemrpsoiubinldi-tryoelfactoemdpmoiucnrdo-srceolpaitcedlelseisoinosnsobisnetrhveedluinngteasntddlaayry2n4x.sacrifice rats, `wThhiecnho-noobsteorxivceodl-oegfifceacltlyleivmeplo(rNtaOnEtLe)fffeocrtsthaitstrsitbuudtyabilsedtoefitnheedfeasst tshuebshtiagnhcesetwceornecednettreacttiedo.n aTthus Efonrvithriosnsmteundtya,lthPeroNteOcEtiLonisAgeqeunicvyal(e1n9t8t5o)tahnedNtOoEtLheanso-doebfsienrevdedb-yadtvheerUsnei-tcefdfeScttatleesvel (NOAEL) as defined by the European Union (1994). Basedon the above NOEL for repeated ifnihnadliantgisoninetxhpeosruesrpeirwaatsor0y.t2ramcgt/omf'.rats exposed to H-24678for 2 weeks, the --~ _-- x35. `CompanySanilized. Daos not cantain TSCA CBI J2H426467788::TTowoo-WWeeeekk IIonbhaallaatiioonnTTooxxiicciittyy SStiunddyy iinnMMaalleeRRaattss -- DDuupboonnt.e8d6s8s5. RECORDS AND SAMPLE STORAGE ALabsoarmaptloeryo,fNtehweatrekst,sDueblsatwaanrcee.waSspeccolilmeecntsed(ifforapaprlcihciavbleep),urrpaowsedsataan,darnedtatihneefdinaatlHraespkoerltlwill be r`eWtialimniendgtatonH,asDkeellalwaLarbeor(aftoorrmye,rlNyekwnaorkw,nDaesltahwearE.eL,. odruaPtoInrtondeMoNuenmtoauirnsRaencdorCdosmMpaannaygeRmeecnotr,ds Management Center). REFERENCES 1. DuPont Haskell Laboratory (2002). H-24678: Inhalation Approximate Lethal Concentration (ALC) in Rats. Unpublishedreper IY | 2. CSearliceusla2t1i0onAdmebsicernibteCdaisncSaideerrIampInascttrourmsenatnsd,CIyncc.l,oBnuellPerteisncp7a-r7at9o-r2s1.91M, Instruction Manual: 3. QCM Cascade Impactor, California Measurements, Inc. Sierra Madre, California. 4. Wickbold, R. (1954). Angew. Chem. 66, 173-174 TM 5. S24n6e-d2e4c8o,r,aGn.dW3.49a-n35d2C.ocThhraenT,oWw.aG.Sta(t1e96U7n)i.verStsaittiystPirceasls,MeItohwoad.s, 6 edition, pp 54-56, 6. Draper, NR. and Smith, Wiley, New York. H. (1981). Applied Regression Analysis, 2" edition, pp 266-273. 7. Selwyn, MR. animal safety (1995). studies. JTohuernuasleoofftthreenAdmetersitcsatno dCeotlelremgieonefTaonxoi-cooblseorgvyab1l4e(-2e)f,f1ec5t8-l1e6v8e.l in 8. Jonckheere, AR. (1954). Biometrika 41, 133-145. A distribution-free K-sample test against ordered alternatives. 9. SLteavreinset,isH.(1.(1O9l6k0i)n., eRdo)b,upspt t27e8s-f2o9r2.equSatlaintfyoorfdvUanriivanecressi.tyCPornestsr,ibPuatlioonAslt1o0.Probability and 10. Shapiro, S.S. and Wilk., M.B. (1965). samples). Biometrika 52, 591-611 An analysis of variance test for normality (complete: 11. Dunnett, C.W. with a control. (1955). A multiple comparison procedure J. Amer. Staist. Assoc. 50, 1096-1121. for comparing several treatments 12. Kruskal, W.H. and Wallis, W.A. (1952). J. Amer. Statist. Assoc. 41, 583-621 Use of ranks in one-criterion analysis of variance. - Tm `Company Sanilized. Doss notcontainTSCA Gil LHLL2244667788::TTwwooWWeecekk nInhhoallaattioonnTTooxxiicciittyySSutuddyyiinnMMaalleeRRaattss_____ DuPonmte8s6s85s ~ 13. Dunn, 0.1. (1964). Multiple contrasts using rank sums. Technometrics 6, 241-252. 14. FNieshwerY,oRr.kA.. (1985). Statistical MethodsforResearch Workers, 13" edition. Haffner, --_ ~~ _-- TH Company Sanilzed. Dogsnotconan 15uA cl ~ ~ TABLES ~ EEE EE oe -- Company Sanitized. Doesn| ot contain TSCA CBI H2-424667788:TTwwooWWeeeekkIInnhhaallaattiioonnTToossiiciittyySStuuddyyiinnMMaaelReatRsats_ -- --_-- TTeABmLEeS ABBREVIATIONS: EXPLANATORY NOTES Chamber ConcentrationsofH-24678 Chamber Environmental Conditions SEM. mg/m* staernrordoftahermedan milligramsper cubic meter 0 - numofbsaemplres `Summaryof Hematology Values RBC - red blceollcooudnt HGB - hemoglobin HCT - hematocrit MCV - mean corpuscularvolume MCH - mean corpuscular hemoglobin --_ MCHC RDW -mreedacnelclodirsptursicbuultairohnewmiodgtlhobin concentration ARET - absolutereticulocyte count PLT - platelet count WBC whiteblcoellocoudnt ANEU - absolute neutrophil (all forms) ALYM - absolute lymphocyte AMON - absolutemonocyte. AEOS absolute eosinophil ABAS absolutebasophil ALUC - absolute largeunstainceldl DuPpoonmtg86s8s5 --_0---- `Company Sanitized. Doesnoscossain[SUA us B2H-A24667T8::TTwwooWWeeekkIInohbaalaattiioonn TTooxriicciityySSttuuddyy iinnMMalleeRRaattss --~ DDuuPpoonmtg8o68sss ---- TABLe ES S EXPLANATORY NOTES (Continued) ABBREVIATIONS (Continued): Summary of Serum and Plasma Chemistry Values AST - aspartate aminotransferase: ALT - alanine aminotransferase SDH - sorbitol dehydrogenase: ALKP - alkaline phosphatase BILI - total bilirubin BUN - ureanitrogen CREA - creatinine CHOL - cholesterol TRIG - triglycerides GLUC - glucose TP - totalprotein ALB - albumin GLOB_- globulin ~ CALC - calcium IPHS inorganicphosphorous NA - sodium K - potassium CL - chloride PFLU - plasmafluoride Summary of Urinalysis Values VOL - volume UFLU - urine fluoride --_ `Company Sanilized. Does not contain TSeo --_ H2L424067788::TTwwooWWeeeekkIInnhhaallaattiioonnTTooxvicciityySSutuddyyiinnMMaalleeRRaattss_ aTABLES DuDuppoomnets86i8s5s NOTES: EXPLANATORY NOTES (Continued) `Chamber Concentrations of H-24678 Particle Size Distribution of H-24678 `Chamber Environmental Conditions Values are reported to 2 significant figures. Means and standard errors of the mean were calculated prior to rounding values. Summary of Hematology Values SummaryofSerum and Plasma Chemistry Values Summary of Urinalysis Values `When an individual observation was were performed on half the recorded recorded as being less than a certain value. For example, if bilirubin was value, calculations reported as <0.1, 0.05 `was used for any calculations performed with that bilirubin data. - ms Company Sanilized. D0usN91CONAN ovr H24678: Two Week Ihalaion Toxicity Study in Male Ras ~~ DuPont8685 TABLE1 CHAMBER CONCENTRATIONS OF H-24678 DESIGN CONCENTRATION MEASURED CONCENTRATION" (mg/m) (mg/m) 0 MEAN SEM. RANGE n 0 0 I [ 2 022 19 0011 013 015-026 9 12-26 9 --_% 20 22% 00338 118 -22 99 a fVraolmuensreexpproessuernets.the mean, standard efoftohemeran (S.E.M., and raonfthegdaelymean values obtained b Valuenotcalcfuomlsaampblelsizee. TABLE 2 PARTICLE SIZE DISTRIBUTION OF H-24678 -- DESIGN CONCENTRATION|EXPOSURE| MASS MEDIAN AERODYNAMIC GEOMETRIC] STANDARD| _% PARTICLES __BY MASS (mg/m?) 02 NUMBER|DIAMETER (um) DEVIATION [<I im <3 sm <0 am 0 21 21 16 68 ND 2 a 8 14 090 21 17 385 100 5898 100 9 10 17 50 98 ND 20 3 0.90 19 5293 100 7 9" 13 Ll 16 22 4328996 N10D0 ab SMienaglneosfa2mpslaempdleetserdmeitneerdmiwnietdh wSiietrhraQICmMpacItpoarcor ND =not determined --~ TT ------ `Company Sanitized. Docs not contain TSCA CBI --~ ZLT224A6Go7T8S::rTTwwoioWWeeceekkIItnnhhaallaayttiioonnSTositcityuStuddy in MyaleiRatsnMuleRas_D_uDupPoo_mns.86_6s8s5. TABL3E CHAMBER ENVIRONMENTAL CONDITIONS DESIGN CONCENTRATION TEMPERATURE RELATIVE HUMIDITY AIRFLOW (mg/m?)* 0 C) 21-21 (%) min) _n 36-67 35 9 02 2 20-24 20-25 51-59 50-56 65 9 65 9 --_--200 1199.24M 37-50 0 50 9 9 Values represent the range ofthdailymean values obtained frnexpoosurmes. ~~ ETE -- Company Sanitized. Doesnotcontain TSCA <5: PN S2H2046778::TTowooWWeeeekk InnbhaallataioonnTTooxdicciityySSuuddyyiinnMMaalleeRRaasls__ DDuuproonmts5e6s85s TABLE4 -- DAYSONTEST MEAN BODY WEIGHTS OF MALE RATS Group 0 mgm? MGEroAuNp BIODY WEIGGrHoTupSV(g) 0.2 mg/m? 2 mg/m? Group VII 20 mg/m? EXPOSURE 0 1 255.1 103015) 2532 118015) 255.1 116015) 2520 10.6(15) 2546 99015) 254.1 10.1015) 2564 119015) 2550 120015) 2 2570 1L6(15) 257.6 12.4015) 2590 105015) 2567 12515) --_ 3 2604 125015) 2598 14.1015) 2620 107015) 2593 13.1015) 4 2613 129015) 2640 147015) 2643 10.9015) 216 12.805) 6 2674 2105) m9 163015) 2745 123015) m3 143015) 7 2705 17.0015) 2755 17.0015) 271.5 13.415) 2734 156015) 8 2754 17.105) 2799 182015) 2815 13.0015) 2743 15.615) 9 2217.636015) 2802 20305) 2826 13.8015) 276.1 17.205) 10! 2585 24.7015) 2584 23.6(15) 2650 207015) 2575 16.7015) --~ -Y Company Senitized. Does notcontain TSCA C8 H24678: TwoWek Inhalation Torisiy Study in Male Rats --_ DuPont. 685 TABLE 4 (Continued) MEAN BODY WEIGHTS OF MALE RATS [a DAYSONTEST ___ 0mgm MEAN BODY WEIGHTS (g) Group Ill Group V 02 mg/m* 2 mg/m? Group VII 20 mg/m? RECOVERY 14 207.1 225010) 2982 23.610) 3053 18.410) 2968 19.5010) 7 3150 3110 3233 318.1 25.5(10) 30.9010) 17.8010) 19.710) 2 3384 3346 3432 3394 25.5(10) 314010) 20.1(10) 222(10) 4 344.1 3388 347.6 3431 417010) 41110) 33.1010) 222010) Das amanged as: SMteaanndard deviation (Number ofvalues included in calculation) "There were no siisticaly significant differences from control tp < 0.05. a Weight lossesdue to fastofirnatgs prior 0 clinical pathology evaluation. --~ -_-- CompanySaniized. Does not contain TSCA Ca HL24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont 8685 TABLE 5 MEAN BODY WEIGHT GAINS OF MALE RATS Group DAYSONTEST ___ 0mgm MEAN BODY WEIGHT GAINS (g) Group Ill Group V Group VII 02 mg/m* 2 mg/m 20 mg/m? EXPOSURE 0-1 18 44015) 31 3.5015) 05 44015) 14 3205) 1-2 37 56 49 17 3.105) 36015) 3.6015) 22015) 2-3 34 22 30 26 2105) 44015) 3.005) 32015) 3-4 10 42 23 23 48015) 44015) 25015) 43(15) --_ 4-6 60 89 102 97 12.5015) 35015) 4905) 3905) 6-7 32 27 31 21 8.205) 23015) 3405) 3305) 7-8 49 44 40 0.9 36015) 25015) 25015) 2.1015) 8-9 12 02 10 18 56015) 4.6(15) 23015) 35015) 9-10 "180 218 "176 "186 13.7015) 117015) 13.1015) 13.2015) - sm Company Sanitized. Does not contain TSCA Gis: H24678: Two:Week Inhalation Toxicity Study in Male Rais ~~ DuPons $685 `TABLE 5 (Continued) MEAN BODY WEIGHT GAINS OF MALE RATS DAYSONTEST Group 1 0 mgm* MEAN BODY WEIGHT GAINS (g) Group Ill Group V Group VII 02 mg/m? 2 mg/m 20 mg/m? RECOVERY 10-14 35.1 73(10) 358 11.200) 352 8.4(10) 37 15.110) 14-17 179 128 180 23 43(10) 11510) 35010) 62010) 17-21 24 2610) 26 60010) 199 43010) 213 62010) 21-24 57 42 44 37 --~ 18.7010) 156(10) 15.5010) 16.510) ! OVERALL 0-10 34 33 104 11 17.0015) 16.215) 14.5015) 9.5015) 10-24 820 763 774 800 16.0010) 18.7010) 14.1010) 12310) 0-24 874 821 912 84.6 34.8(10) 34.5(10) 282(10) 18.2010) Dats amanged as: SMteaanndard deviation (Numberofvalues included in calculation) # Statistically significant difference from control at p < 0.05 by JonckheereTerpsira trend st. a Weight losses due o fasting ofrats prior o clinical pathology evaluation. --~ -- = `Compa--ny Sanilized. Does not-- contain TSCACBI : : 5XH : i cL. :1! .el353: &8 &8 | 38a os ) I HI8I2 Ss a g 3 or ii: : we | 41 ~ Z58Elz = = i#1i3s : FREES | 381 " oO ov gf 32 5 32 a 5 s1 i:: gfii:re3 H i i2 ~i 22 21 41 32 342 2% 3 28% Eiidi 2i H24678: TwoWeekInhalation Toxicity StinuMldeRayts -- DuPont.8685 TABLE 7 SUMMARY OF BLOOD FLUORINE ANALYSIS Group T DAYSONTEST___ 0mg/m . BLOOD FLUORINE (ppm) Group Ill Group V 0.2 mg/m? 2 mg/m? . . 3 : 2 + 9 13 0.04(5) 14 0225) 14 0.15(5) % 16 023(5) . : Group VII 20 mg/m? 16 0.05(5) 21 03205) 200 0.115) 15 0.135) --~ r --r-- te-- e ----ae esiee ---- Dataarnged as: MSteaanndard deviation (Numofbvaelures included in calelation) * Statistically sigificant diference from test day 9 control at p = 0.05 by Student' Test. a Samples not evaluated fortis imepoint. --~ -- CompanySanitized.D-- ocs not c-- ontain TSCA CBI | HE24678: Two Week Inhalation Toit Study in Male Rts --~ Dupon685 TABLE 8 SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS TEST/ PERIOD Group 1 0 mg/m? Group Ill 0.2 mg/m Group V 2 mg/m? Group VII 20 mg/m RBC (x10%4L) DAY 10 6.98 7.16 7.30 7.18 0.27(10) 0.24(10) 0.31(10) 0.50(10) DAY 24 7.38 732 747 742 0.19(5) 0.17(5) 0.284) 0.33(5) HGB (g/dL) DAY 10 148 15.1 15.1 15.0 DAY 24 0.4(10) 153 0.4(10) 15.3 0.5(10) 15.0 0.7(10) 148 HCT (%) 0.3(5) 03(5) 0.5(4) 0.2(5) DAY 10 443 453 456 45.0 1.3(10) 1.2(10) 1.9(10) 2.4(10) oa MeVDA@Y 24 450.6165) 4046765) 44.14864) 4312965) DAY 10 63.6 63.3 62.5 62.8 DAY 24 2.0(10) 61.0 2.1(10) 61.1 1.2(10) 59.4 2.2(10) 59.3 MCDHA(Ypg)10 DAY 24 MCHC (g/dL) 1.05) 20150310) 200.6705) 1.2(5) 212 0.7(10) 2005965) 144) 208 05010) 200.144) 2.9(5) 210 0.(10) 201016) DAY 10 335 334 332 334 DAY 24 RDDWA(Y%)10 390.4(10) 0765) 122 304.23(10) 075) 124 304.03(10) 0.464) 124 570.6(10) 090s) 125 DAY 24 0.4(10) 120 0.5(10) 119 0.6(10) 118 0.4(10) 122 Pa 0.2(5) 03(5) 0.6(4) 0.4(5) ee mCompi anye Sanitized.Dtoees neolctonleairn TsSC,A CBI 124678: Two-Week Inhalation Toxicity Study in Male Rats ~~ DuPont 8685 `TABLE 8 (Continued) SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS TEST/ PERIOD Group I 0 mg/m? GroupI 02 mg/m? Group V 2 mg/m? Group VII 20 mgm' ARET (1041) DAY 10 180.5 2100 2078 198.0 36.9(10) 483(10) 19.9(10) 46.5(10) DAY 24 2343 28965) 283 3385) 2134 19.44) 2348 2675) PLT (x10%4L) DAY 10 1162 1183 1335 1217 173010) 207(10) 93(10) 249) DAY24 122 1189 1368 1319 1850) 2062) 584) 96(4) WBC (x10Y4L) DAY 10 14.89 13.87 13.47 1351 2.35(10) 4.14(10) 234(10) 3.0710) ~~ DAY24 1072 1048 10.03 10.18 f 144(5) 3325) 1.5864) 34805) ANEU (x10%4L) DAY 10 202 150 1.64 1.79 0.8310) 04510) 0.40(10) 0.38(10) DAY24 192 167 157 1.88 0.46(5) 0.55(5) 0514) 0.425) ALYM (x10%4L) DAY 10 1228 11.75 1.23 1.02 DAY 24 1.62010) 834 405(10) 8.40 282049(10) 27.8823(10) AMON (x10%4L) 125(5) 26465) L174) 296(5) DAY 10 027 032 030 030 0.15(10) 0.16(10) 0.13(10) 0.12(10) DAY 24 025 021 014 022 0.1165) 0.1465) 0.034) 0.08(5) AEOS (x10%uL) DAY 10 01 009 0.13 021 005(10) 0.05(10) 005(10) 0.19(10) DAY24 010 0.10 009 010 0.115) 005(5) 0.034) 0.05(5) -_-- `Company Sanitzed. Does nol contain TSCA C81 HL24678: TwoWeek Inhalation Toric Study in Male Rats --~ DuPon 8685 `TABLE 8 (Continued) SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS TEST/ PERIOD Group 0 mg/m? Group Il 0.2 mg/m? Group V 2 mg/m? Group VII 20 mg/m? ABAS (x10%uL) DAY 10 DAY 24 ALUC (x10%L) DAY 10 DAY 24 012 00710) 005 0.045) 0.09 0.05(10) 006 0.05(5) 011 0.04(10) 005 0.035) 0.10 0.0510) 005 0.02(5) 010 00.0095(10) 0.044) 0.06 0.02(10) 0.06 0.034) 010 00.0075(10) 0.035) 008 0.0310) 007 005(5) --_ Duta armanged as MSteaanndard deviation (Number of values included in calculation) There were no satisteally significant differences from control at p<0.05. --~ -_-- Company Sanitized. Does notconlain TSCACBI H24678: Two-Week Inhalation Toricity Study in Mile Ras ~~ DuPont 8685 TABLE9 SUMMARY OF SERUM AND PLASMA CHEMISTRY VALUES FOR MALE RATS TEST/ PERIOD Group 0 mg/m? Group IT 0.2 mg/m? Group V 2 mg/m Group VII 20 mg/m? AST (UL) DAY 10 % % 9 103 10010) 12(10) 15(10) 1210) DAY 24 100 95 87 20 ALT (UL) 125) 175) 16) 6) DAY 10 38 39 39 a 8(10) 710) 6(10) 5(10) DAY 24 38 " 48 39 365) 565) 265) 65) SDH (UL) DAY 10 121 114 124 125 ~ DAY 24 34(10) 122 20010) 13.1 3.8010) 12s 1257010) ALKP (UL) 4765) 3805) 225) 3.805) DAY 10 27 258 29 261 DAY24 1810) 219 4710) 213 57(10) 185 64(10) 219 BILI (mg/dL) 305) 5065) 3165) 4165) DAY 10 011 0.10 0.10 010 DAY24 0.03(10) 013 0.03(10) 009 0.03(10) 011 0.04(10) on BUN (mg/dL) 0.035) 0.0365) 0.045) 0.05(5) DAY 10 16 16 1s 13+ DAY 24 2(10) 2(10) 2010) 2010) 16 14 15 13 CREA (mg/dL) 25) 165) 15) 15) DAY 10 024 028 025 027 DAY 24 0.03(10) 031 0.05(10) 029 003(10) 036 00.2095(10) 0.045) 0.05(5) 0.1365) 0.035) --~ - --. Company Sanilized. Does notcomain TSCA Gl H2HLA26467788:TTwwoo-WWeeeekkIIbnahallaaitoinonTTooxriiccittyySSutdudyyininMMaalleeRRaatiss ~~ DDuubPoonmts8e68s5s TABLE 9 (Continued) SUMMARY OF SERUM AND PLASMA CHEMISTRY VALUES FOR MALE RATS TEST/ PERIOD Group I 0 mg/m Group II 02 mg/m* Group V 2 mg/m? Group VII 20 mg/m? CHOL (mg/dL) DAY 10 66 62 1200) 12(10) 61 1100) 57 12010) DAY 24 EY 105) 61 65) 6 565) 62 1405) `TRIG (mg/dL) DAY 10 a 1510) a1 13(10) a" 5(10) 46 1300) GLUDCA(Ymg2/4dL) 17a65) 25135) 51585) 2562(5) DAY 10 86 86 82 85 ~ DAY 24 5(10) 91 6(10) 88 (10) 92 410) 9 TP (g/dL) 16(5) 1265) 6) 65) DAY 10 . 6.1 02(10) 62 02(10) 6.1 03(10) 6.1 02(10) DAY 24 65 64 63 63 ALB (g/dL) 0205) 03(5) 04(5) 0.5(5) DAY 10 41 02(10) a3 0.1010) 42 0.110) al 02(10) DAY 24 GLOB (gdL) 44 0205) 44 0.2(5) 43 0205) 43 02(5) DAY 10 21 20 0.1710) 0.110) 20 02010) 20 0.110) DAY 24 21 20 20 20 CALC (mg/dL) 0.165) 0.15) 025) 0365) DAY 10 16 0.2(10) 116 03(10) nr 0.4(10) 116 0.310) DAY24 10 02(5) 110 0.6(5) 109 04(5) 10 04(5) --~ =e Compan-- y Sanitized. Does no-- t contain TSCA CE! DH22476878::TTwwooWWeecekk InnbhaalluaitioonnTToxoicictySSutuddyyiinnMMlaeleRaRtoss ~~ DDuubPoownts8e6s8s5 TABLE 9 (Continued) SUMMARY OF SERUM AND PLASMA CHEMISTRY VALUES FOR MALE RATS TEST/ PERIOD Group! 0 mg/m? Group Il. 0.2 mg/m? Group V 2 mg/m? Group VII 20 mg/m? IPHS (mg/dL) DAY 10 105 0.5(10) 107 0.5(10) 109 0.6(10) 105 0.710) NAD(mAmYol2/4L) 100.26(5) 092265) 099665) 09.87(5) DAY 10 148.5 22(10) 1492 2.1(10) 149.4 19(10) 1500 2.110) DAY 24 K (mmol/L) 1473 1365) 147.1 1565) 1472 1265) 148.4 116) DAY 10 607 0.24(10) 620 039(10) 614 0.22(10) 6.16 0.4210) ~ DAY 24 592 6.13 6.09 602 CL (mmol/L) 0.4565) 046(5) 049(5) 025(5) DAY 10 1025 24(10) 1029 3.810) 104.1 1.7010) 105.0 28010) DAY24 PFLU (ug/ml) 102.4 345) 105.1 2.565) 1042 3.05) 1048 155) DAY 10 00 0005) 00 0065) 00 00(5) 00 00(5) DAY 24 [8 0.04) or 0.004) ol 0.0(5) ol 0065) r---------- enea-- ------r ---- Duaamanged as: SMteaanndard deviation (Number of values included in calculation) * Statistically significant difference fromcontrol at p < 0.05 by DunnetTamhane-Dunnet es, 3 Company S~anitized. Does--not contain TSCA CB! H24678: TwoWeek Inhalation Toxicty Study in Male Rats ~~ DuPont8685 TABLE 10 SUMMARY OF URINALYSIS VALUES FOR MALE RATS TEST/ PERIOD Group 0 mg/m* Group Ill 0.2 mg/m? Group V 2 mg/m? Group VII 20 mg/m? VOL (mL) DAY 10 DAY 24 UFLDUA(Yug1)0 DAY 24 -_-- 72 3610) 52 37(5) 83 22(10) 10.1 26(5) 79 62(10) 8.1 44(5) 79 24(10) 25 44(5) 93 3310) 93 3.105) 81 12(10) 127 2605) 93 10.6(10) 108 6.505) 105 4.810) 140 25865 -- Daaamanged as: MSteaanndsrd deviation (Number of values incladed in calculation) "There were no saisially significant differences from control at p < 0.05. --~ a Company Saniized. Does notcontain TSCA CBI E224667785: TTwwooWWeeeekk IInnhhaallaattiioonnTTooxiciitySSttuuddyyiinnMMaalleeRRaattss --_ DDuuPobnt8o68s5 TABLE 11 MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 10 SACRIFICE Group 0 mg/m? Group Tl 02 mg/m Group V 2 mg/m? Group VII 20 mg/m? MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) LIVER 8.241 120965) 7.898 1.20265) 8.145 05155) 7.384 1.00265) KIDNEYS 229 0.179(5) 2315 0.445(5) 2240 0.245(5) 2335 0.376(5) LUNGS 1.504 0224(5) 1.606 0.2625) 1.554 0.138(5) 1572 023965) BRAIN --_ 1890 0.106(5) 1934 0.096(5) 1870 0.100(5) 1912 0.036(5) TESTES 2950 0.20005) 2992 0213(5) 2862 0.358(5) 2742 0403(5) FINAL BODY WEIGHT (grams) 251.440 18.258(5) 250200 18.931(5) 254.680 1420165) 246.280 153275) --~ er eT s SompanySanitized, Doss notcontain TSCA CBI 24675: Two-Week Inhalation Toxicity StudyinMale Rats --~ DuPont 8685 TABLE 11 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 10 SACRIFICE Group 0 mg/m? Group Il 0.2 mg/m* Group V 2 mg/m? Group VII 20 mg/m? MEAN RELATIVE ORGAN WEIGHTS ( % of body weight) LIVER! 3.269 FINALBODY*100 ~~ 0.339(5) 3.146 0342(5) 3.197 0.046(5) 299 033065) KIDNEYS/ 0913 FINALBODY*100 ~~ 0.027(5) 0921 0.1245) 0878 0.055(5) 0.947 0.134(5) LUNGS/ 0.600 FINALBODY*100 ~~ 0.092(5) 0.642 0.097(5) 0611 0.057(5) 0.637 0.073(5) --_ BRAIN 0754 FINALBODY*100 ~~ 0.060(5) 0776 0.062(5) 0735 0.025(5) 0778 0.038(5) TESTES! FINALBODY*100 ~~ 1176 0.075(5) 1.198 007165) L121 0.087(5) L112 0.125(5) --~ DL a `Company SanitizeSd.eDoes not containTSCA C81 24678: Two-Week Inhalation Toricity Study in Male Rats --~ DuPon8685 TABLE 11 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 10 SACRIFICE GroupT 0 mg/m? Group IT 0.2 mg/m Group V 2 mg/m? Group VII 20 mg/m? MEAN RELATIVE ORGAN WEIGHTS (organ to brain weight ratio) LIVERBRAIN 435.438 54.098(5) 407.488 56.895(5) 435.622 12.9335) 386.133 51.265(5) KIDNEYS/BRAIN 121.614 9.622(5) 119.407 20.504(5) 119.535 7.755(5) 121.908 17.942(5) LUNGS/BRAIN 79.378 8.14005) 82699 9.683(5) 83.078 52155) 82.141 1177265) ~ TESTES/BRAIN 156.562 14.659(5) 154.661 7.589(5) 152.815 14.1675) 143359 20.667(5) Dats aranged as: `MSetaanndard devision (Number of values included in calulation) `There were no statistically significant differences fom control at p< 0.05. --~ _-- or Company Sanitized. Does notcontain TSCA CBI H24678: Two-Week Inhalation Toriciy Study in Mle Rats ~~ DuPont 8685 TABLE 12 MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 24 SACRIFICE Group 1 0 mg/m Group Ill 0.2 mg/m? Group V 2 mg/m* Group VII 20 mg/m? MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) LIVER 9.082 0.9614) 9.366 12974) 10376 0.404(5) 10477 0.975(5) KIDNEYS 2644 0.246(4) 2636 0.2044) 2761 0219(5) 2855 0.243(5) LUNGS 1623 0.2014) 1.633 02044) 1.840 0.264(5) 1.695 0.1315) ~ BRAIN 1.991 0.02764) 1949 00524) 1976 0072(5) 2023 0.11465) TESTES 3.244 0.1774) 2813+ 0.1504) 3.209 02615) 3.77 0258(5) FINAL BODY WEIGHT (grams) 310.600 13.8494) 316.900 33.9004) 321.560 113415) 339.160% 22.606(5) --~ = `Company Sani--tized. Does not containTSCACB! 12H4-2047687::TTowooWWeeeekkInnhhaallaatiioonnTToouxiiccityySSutuddyyiinnMMalleeRRaattss ______ --~ DDuuPboonntd86s8s5. `TABLE 12 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 24 SACRIFICE Group 1 0 mg/m? Group III 02 mg/m* Group V 2 mg/m? Group VII 20 mg/m MEAN RELATIVE ORGAN WEIGHTS ( % of body weight) LIVER/ 2923 FINALBODY*100 ~~ 0.263(4) 2952 02014) 3231 0.186(5) 3.085 0.11165) KIDNEYS/ 0.851 FINALBODY*100 ~~ 0.065(4) 0835 0.067(4) 0.858 0.056(5) 0.844 0.0815) LUNGS/ 0523 FINALBODY*100 ~~ 0.065(4) 0517 00554) 0573 0.087(5) 0.502 0.064(5) --~ BRAIN/ 0.642 FINALBODY*100 ~~ 0.036(4) 0620 0.066(4) 0616 0.044(5) 0.599 0056(5) TESTES/ 1.047 FINALBODY*100 ~~ 0.103(4) 0893 0.07004) 0997 0.064(5) 0942 0.1235) --_ - `CompanySanitized. Does not contain TSCACBI H24678: Two-Weak Inhalation Toricity Study in MaleRais -- DuPont8685 TABLE 12 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 24 SACRIFICE Group 0 mg/m? Group I 0.2 mgm* Group V 2 mg/m? Group VII 20 mg/m? MEAN RELATIVE ORGAN WEIGHTS ( organ to brain weight ratio) LIVER/BRAIN 456.224 479199) 481.160 7133004) 525.254 19.394(5) 519.153 53.128(5) KIDNEYS/BRAIN 132.855 12.5794) 135373 12.688(4) 139.973 14.129(5) 141.244 10.200(5) LUNGS/BRAIN 81.485 9.8624) 83.779 100074) 92973 11872(5) 83911 6.8935) --_ TESTES/BRAIN 162.866 6.8014) 144.282 531004) 162.765 17.763(5) 157.389 14.494(5) Dusamangedas: SMteaanndard deviation (Numofbvaelures included in calculation) +# SSsuttiscicaallll ssiggnniifficcaannt ddiifffferreennccee rroomm ccoonnttrooll aatt pp << 00..0055 bbyy praernadmettersti(cTtoensctk(lDeuenrneetTterTpasrtrhaa).re Dunnett). --_ -_-- `Company Saniized. Doss not 2332in TSCA CB) 8 ~3 32 (p5r1e5y7, aTuon T on 0e2e 0 2020on | E pepETEweRaE e eeTa E a ; EE oe a (ioln! 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Fe am 2go i11g : 3 : lpi 2 gg STile $F iisFs i| i33 I i FL P-L jit Tg 3 ~ E2Q8E S5 g92 || J:iJ i1i[158g434% 3: 245g2xd || ]: 8 ii{1nsd nN i E FE 00i d$iF $13 iidse; :i :g Po : pgiHd g[pdRET 4| 6 0| i EggB8E2 E E4 H dg I[1.7 gi } 0.82 4 w EB 27.4 31: 005Zz i0| , IP; p EodEg4l3aE5B3o8noE88d 5BF hO0EEEEioDF niI1EC4S : & | gn gETERU Eg i PBs 3: ok iPBB D1 fE BBSEE OB ! --_-- | 88 ZBEo p8 ogZou [1I5f8 E{F 3 i1f3g & ~3 popeerermeneeeeomn 82 i BET soz aon Fn i 2 : Jos _ i EE g BisEs Gn vv Go om | i 5 z ss, i pgm EL Toe Fy TE g fem ed 31 gi iE IIEM xgg iPfOiEE |i 51153s3 isSu l|i iEEg ~ cfaecl| : i2 <. 5 2X1 ii 3 g8t% | | sg ilafd SE tian i: g :qa LfogFs RFEOE oEaE rd go: g g bir H CE op prof opildoidf i32 ggs i|1. ipeA]: galas 5fgiEaas $i iis Ef 28 By :i : SlPF Eigied ged i PB: ef f kIDE g ii ~ fr3z i --_-- RE ~3 : BT ET 5 wn ge 2m ow | A i (HIRES) - TT i < Py oa 4 1 Ji 8 gin 2 : is 1 2 iii 19ic8ni = RE = Hr H3 =go ois iiii | ELE iH i 3Is8gt | iei 1in 2s ~ : 8285 | |: EifEy : = 22 | i ii # 3 Bx | ii 22 8 | || ij1223 Ig | i ig i15g i i| 23 is 1 0 Fb iiiiin | zd iF EE OE BosE ity H ag | {{85 5Ei..83%fp9 8og goa5r !a08 5 i 8gi| ;{52 g2i3z5da 3ig3 iH83 iiEs i ELE pd ay fail i2 [i8 pigsg#ed flefere 5k EE 8 id id, ~3 oo | z: 3. g 1: # ~J i1f3i7n8g.g]0 Bamo Bme 0a8n aEe 8oo Ee gigI i 32 f 5 hHie me 2 5Eol a s p en evee o Ee ged | gCA ol! i{i1 gE ii ITP z G2EE 8 |} Yei; 4iH12o% = sg | : Ee 8i i 188 22 gg:Edx |i iii iiiiEg g a i! 01 F88EE8 BEE gEgEEi% BEE ida lal ge ERE i a IE BT % 25 8 ERI 8 15% fA ZF FZ FRO OIGE -; 2 fl | {18g1i.s8n.E1] 50 Z8e G8ee oomn= g3nn} Ee g:ii 15108 go i i 53 iEiaowki a ~ iit i 2 EHloy mi oo g Be = lig ii 11 ~ sPE : oC ylT | = gy -- 54C5oki sx | || 8 OZ i BEHF1e2Ht3] 18s lee 132 xi111]; : . B g JHH 3 : : & | ] iyiE i: 1i88 i! Pio ] Z: ilof| ii Ely |fle sopTg: tfp ziidH C| E E BE, d gEeppFEBEEEof iiea hagrheeLE IdlH |122kRE J 2 oEREEST EH :; ~ : 2 : if]i:bfe E rfeEHes fet iiEed mmm mms eeeees ~ 3 SE ~ 23 HEL 181 EL} a = i :" EET 2 igioR| | 2 f o Ean Ti1 2g gio fe 12 3 gE id 3 2 inioEm 15g gj sig id | gE i3t gE ii ! Ig i 3 LQ HE p-- 35 | | 2HT 133 - | i% zga 8z8%89 || i|} i1[i85s%8 = 3g z3l 4dg 3: i ot = 2 | ii iie 35| Pi oga egme i14E4 EFBI iPyRBBgfRaEiElNt eg P0 oEog FPe82E38E ECEEEOEES Eet a If iad id fF Beg 3af [2 E } EE EREE i NT ~ 3 piesa 3 | [Li i } ig] &, Frove Boom ome 8 ELI | 3 EE i z PBiaEst od i Poe fs i IE ee eee ] 5 Ey i } PPiol iTE2m a. I em RT 3: Be 3 giPPL iigg i & iE ii5in2 {5 Sg | | iy EERIE ig 1 3 : g#B 20 y i1 ir F::E }ii gE; Ii2 I i i Eg i i s:ggiEifs g4E00E%3 0E% iE idiss Bgyor3 gia df 5h sah 1: i :: ~ gij i iPB jE EgBoeadth Ep Bi 580.E3.0E4 180ai1E 184k02 iDOB iEfg8eR BghEiE f iIi en FEt iE ~ i1 rrr 5 EE {iggigOE,s| E Bo BE on E Be wer = B8oB r :i ssl Bi rm} ! Eoin iat -- ;: EL 1 : z2 B ihT eeeTo os 1ie 1] gE {-j--i T iE ; 2gl iiEE | 3a f J 5g iE iBEh ~ 1 I Teg at (iin J i| i138 123 iif :: iis ; i i od 18g : i Po It it :] : | iPEgEg E gi fog ihff : geoo |Ly BOFi EESEEE g iif.d ; i EEE Eg * g 8 Eos pid BEE i;i: PoPEssge gae ge it iEsEE EE RBEEfLk ~ i FIGURES ~ rememeee ---- ------TM-- Compan-- y Sanitized. Does-- not contain TSCA CBI Po t5 : 3 t i [LI] D: i ; i Y _g211 ~~ Eg g 23% a |8 i: 3 |J Uii] 3i i ogoi alt1 4H | 2t || z| ~ ge 5 Hi 2 ie ig gl ` IB* i' :: SL : ` ~ od 8 z SFE vet: wip poy ues. g ~3 :2 = a ~ g z g 2 Z i i 11547d% &: i : : i3 2 8 = > :. i CT Eg 2 2 : --- i a 5 8 2 2 3.8% 3% 5 3 TTT coseseew HOHL2T46S78:TTwwoo-WWeeekk bInlhatliatoionnTToxvieityySStuudyyiinnMMaaleeRRaatss Dwuroonw6s85 --_ APPENDICES -- mommi ee ee s Te Company Saniized. Does riot contain TSCA CBI STHL24R678: TTowoo WeoeokkMInhhaallaatvioonnTToovxiicciltyySSutdudyyininMMaalleeRRaattss ~~ DDuuoPomngt8e6s85s --~ APPENDIX A Daily Chamber Concentrations ~~ _-- Toe `Company Sanitized. Doss not contain TSCA CBI H1L2244667788::TTwwoo WWeeeekkIInnhhaallaattiioonn TTooxxiicciltyySSttuuddyyiinnMMaalleeRRatass ___ --~ DupPoonncts8e6s85s -- DDAAIILLe YYCCHHAAVMEBEERRCCOONNCCEENNTTRRAATTII. OONNSS oe ABBREVIATIONS: EXPLANATORY NOTES SD. - standard deviation mg/m? milligramsper cubic meter n - number of samples FOOTNOTES: a Chamber not sampled on this day. b Value not calculable from sample size. NOTES: --_ Values are reported to2 significant figures. Means and standard deviations were calculated prior to rounding values. eer ------------ reese ess "0 Company Sanitzed. Doss no conan TSCACE! g a | sseasraisiasnansss i Hees i iE aE : Jl] sme 8 Ff Fld zsamzsstazs 1i ~ H-24678: Two-Week Inhalation Toxicity Studiyn MleRats DuPont8685 PS APPENDIX B Daily Chamber Environmental Conditions --~ ---- ee Ts -------------- `Company Sanitized. Does notcontain {54. - ZLHZ2E4O6T7S8::TTwoooWWeeeekkIInnhhaallaattiioonnTTooxxiicciittyySSttuuddyyiinnMMaalleeRRaattss --~ DuDPuoPomnetf8e68s5s wm DDAALILYYCCHHAAMMBBEERREENNVVIIRROONNMMEENNTTAALLCCOONNDDIITTIIOONNSS ~~ ABBREVIATIONS: n number of observations EXPLANATORY NOTES FOOTNOTES: a Due to technical exposure. error, samples were not taken for approximately the first2 hours of the b Due to technical error, false readings were omitted. NOTES: Values are reported to 2 significant figures. -- Means and standard deviations were calculated prior to rounding values. --- = Company Sanitized. Does not contain TSCA CBI ~ . 2 : lait asans 2 Ee j ~ | Ie | Ewens eEaaee : | ies ] J ~i [ ssn 5 ~3 8 -Sheeaann l5o2 rammzain = Hm : 5 RRTIRIIT 8 5 Femmmanz i |e POSSE JH foeieae 2] i RIARNIBIZ 3 Hp : Rick 5 [f esesesas ij ~ 5 ee I jl ] fH fan EI eceorens i i jo i Fue a : & H2L4246G7786:: TTwwooWWeeeekkInInhhaallaattiioonnTTooxvicetyySSutuddyyininMMaalleeRaRattss DuDpuoPonncts8i6e8s5s APPENDIX C Individual Body Weights PN TTTTe Company Sanitized. Does not contain TSCA CB 2H2L20467788:TTwwooWWeeeekkIInnhhaallaattiioonnTToodriiclittyySSutduydyininMMalleeRRaattss ___ --~ DDuuPPoonntc8s6s8s5 --_UDIIV NDIVI IDUALD BODU YWWEEIIA GGHHTTSSL ~B ~ ODY FOOTNOTES: EXPLANATORY NOTES a Weight losses due to fasting of rats prior to clinical pathology evaluation ~~ ~~ Teen, ompany Sanilized. Does not contain TSCA CB smessrmsssenmerey LfeLr Llblbbhimon mma 8lbEfff E bolibbhbihbhibouin - i Hon |oommmisENs Uf, : 3 i ~&| CE[ & ~ jg % 3 8 . gussasnsnesaoee i f Po; gopssiziegsssns 2= iy 80) GiRdvaseaniiua 5 Aeeremnann anna i huhbhemnan : ii i? nl ifo; GdEeRRdIRREEIRiEEiREEEER iIsD gq i id 2? 52.3 fanizfacsimimgudmasminsaand.e. f.0 RRERAEERAE RER Gdfiidnnas ii gi | 5 SgEESESEiIgsLeE 3 1-- 3 EggEEEIiiassest ~3 | i2:. gEdRsEnaIERsEEiRmIiIaIn ;L2y3 gmmsm ROTIm : rzasanaes 3 i EERSZSRARIEARAL 3| | _. | 1 Hag "4 io ssn be : i ; BHEREIEREREERES : 3 sem - 5| ii;o R SR eaR d i ig I ii- a | FASE 10 HEHEES ~3 3 Loop HHRaANiRAEdANeESsR m |i i L. mmm if.p KEERRREENLN i| 3 wn} as s ieop aERRt RISRStRRSEaNSE 103 - i Hiisanting :1 3 37 FheERSR 3 5 for BERIRSAAREREERR 3 13 ifp [ SRRRe RARRREe RRRER [GSdag g #iisateaes fmiadntaieeantdgse 2H:2240678:TTowooWWoeoekk IInohhaallaattioonnTTooxxiicciltyySSutuddyyiinnMMealleeRaRattss DDuuPPoonmts8i6s8s5 . APPENDIX D Individual Clinical Observations and Mortality Records -- -_-- i. Company Sanitized. Doss not contaiinn TSCA Usl ZLF2-02406T788:: TTwoooWWeeeekkIInnhbaallaottioonnTTooxviicietlyy SStuuddyyiinnMMaalleeRRaattss DDuuPPoownsti8e68s5s -- Individual Clinical Observations and Nortality Records Sex Grow animal Observation Days MT 6628 G7HeaamiorrOabLlsosesro,vbasteFiroovvnaestl.iiosnbB,,lNedBoilvAaimtaoerreamblailailtyfDoetceLcitnedFath, Lee =i10 HSAtEenLotses, oFyorSepheart,inBilateral a%ie MX 662483 GESeylmeeerOribetsdiecroovbdaetsbiryovnadste,isoinoB,nletdovAibamOorrbmiatlailtyfDoretCelctiendPath, Left 0i110 MT 66284 GvSeleneerrOlabeslieeronvbaastehiryovnaGsta,ioinBn,letdoviAamoSmembailtiatlyfDofetceLcitnedFath, Lee 01110 MX 662485 GBS eynoerOae blsarovbasteirovnaest.iomnB,lvedovAimameOrrmbailtiatlyfDorecCelcitnedPath, Loft 0k1d010 WT 66286 GESveaoemieSerbiaoeaerbsve'aetsriyvoandtsair,oianBn,i'edNoviAabmOorrbsiatlailtyfDoretiecitnedFath, Left 01i-10 HI 682487 GEEevfnoeeOrOnabilseerrovvbaastteiiroovnnasst,.ionBB,lleeNddovviiAaabnOoorrrbbmiiattlaailltyffDoorrecCCellciicnnedPpaacthh,, RLiagthet 0a102 AG Tea po Wr Gems GvEveaanerOObabssleerrhvveaaettriivoonanscs,i,onBB,lleeddNovviiAaabnOOorrrbbmiiattlaailltyffDooerrtiieciitnnedPpaatchh,, LKeaotnee 0i2o-2 Seelelea sy darian' a ~ MX 662085 GEEevsneeOOrbnascleorrovvbaastteiiroovnnasst,.ionBB,lleedMdovviiAaabnOoorrrbbmiiattlaailltyffoDorretcCellciitnnedPpaocrhh, KLaitsee 021%024 iSurgetey i 1 662090 GEBev7no0eOrOhabslseerrovvbaastteiiroovnnasst,,ioniB,leedNdovviiAaamoOOrrrmbbaiilttiaalltyffDoorertGCellciitnnedPPaacthh,, BLoifltateral [5i4= Sierras dean a MT 62451 GEBeyyneerOOabblsseerrhvvaaaettriivoonansts.i.onBB,lleeddNovviAialamOoorrrbbmiiatvlaaillcyffoDorretCcellciitnnedPpaatchh,, ALiegftht ioaom . Secriticed by desian 3 WoT eas: GSeincetriaflicoebdsebryvadteisoina,nNoAmomaiicy Detected 02-26 MoI 662093 GSeeneerrlatlicosdhasbryvaatnisoino,n No morality Detected 0224 t ces gSeencerriatlicoobds'esryvadteisoino,n No Abmomalicy Detected 02-2 MT 662495 GSeimcerriattieosbdsebryvadtoisoino,n No Abmorsalicy Detected k0n.20 MX 6623 GSeincerriatlicoebdsebryvadtaisoina,n No Abnormality Detected 02%.24 --~ -_-- oi CompanySanitized.Does nol contain TSCA CBI H2244667788::TTwwoo WWeeeekkIInnhhaallaattiioonnTTooxxiicciittyy SStuuddyyiinnMMaalleeRRaattss ___ ~ DDuuPPoonntf8i6s85s individual Clinical Observations and Wortality Records Sex Group Animal Observation Days. MI 662097 SGEeytneeerriOatblisecroevbdastebiryovnadste,isoingB,lneNdoviAabnroromiaaliltyfDoertCeLcitnedFach, Late i010 MII 662495 GSEeylneeerrOlabelsieerovnbastehiryovnadste.ioanBn,ledNovAibanOorrbmiatlailtyfDoertCelcitnedPath, Lote i10-10 WII 662099 SGEevnaeerGeahlsleroevbastyerLvoaasts,iioanS,nledKovAibanGorrbmiatlailtyfoDfetLecitnedFath, Lete 03io:10 MII 662500 SEGevtnaoerOribetsliecroevbdastebiryovnadste,isoingB,nleNdoviAasmOorrbmiatlailtyfDorecCelcicnedFath, Left iE0S-10 MIX 662501 SEGveteneerriOabelsieoroavbdastetiryovnadste,inoinSm.iedNoviAabnoorrbmiatlailtyfDoertCeicitnedPath, Lets i10-10 WIT 662502 yBGe7an0erCOahblaseehrrvveaastteiiroovnnassi,:onBB,lleNeddovvAiibaanoOorrmmbbaiilttaailltyffooDrretiiaciitnnedFPaacthh,, hLootnee F00y-20 Aeidantally willed i MII 662503 GEEeoynerOOahblnsaerrovvbaastteiiroovnnasst,.ionBB,lleetddovviiAaabnooorrrbbmiiattlaailltyffoDorretCcellciitnnedFpaatrhk, RLiogthet a10-2 Sicriticon by desian i ~~ MII 62504 YG7eoaneOrOnabslsoerrhvveaasttriivooannrssi.,onBB,lleeddNovvAiibaamOSorerbbmiiattlaailltyffoDorertCGo1lctiienndPpaacthh., KLoitseh Sieriticed by design b10y0-26 3 MI 662305 GEEevonaerOOanblcsaerrovvbaastteiiroovnnasst,.ionBB.lleedNdovviiAaabnororrbbmiiactlaailltyffoDorretccellciitnnedpBaacthh,, Rtiegcht iS iey i20-24 i HII 662506 GEEyeoen'erOOabblssaerrovvbaastteiiroovnnasst,,ionBS,leeddNovviiAaabmoOorrrbbmiiattlaaillcyffoDorretcCehlcitinendpPaatchh,, RLiogthet Sel een a01-24 3 NI 662507 GSeincerriatlicoebdsebryvadteiosni, No Amormality Detected 20-24 MII 662508 DG[iasmcerhraaralgeo,rbseNiorsvsat,tioyBnl.ackNo Aosmality Detected 2i0)102-2 MIE 662509 SGiecnteirfaicoebdsetryvadteiosnc, No Abmormality Detected 20.24 MIX 662510 SGoimcerriat)icoebdsebryvadteisoino,n Mo Abnormality Detected 20%24 MOI 62511 GSeenreirEailcoodbsesryvaSteisoino,n No Abmommality Detected W02 ~ -_-- i oe Company Sanitized. DoesnotcontainTSCA CBI 24678: TwoWeek Inhalation Toricity Studyin MaleRats DuPont 8655 --~ Individual Clinical Observations and Mortality Records Sex Grow antral Observasion Dave KV 62512 B EGyeenGehraL aolrvoabtseornvaSst,ionnB,leYdovNieoromrabiltiatlyfDoeftcelcitnedFath, tate H10S10 NV esis GFEeraneierGeThloavsear,bastoFriovoranetpsiao,nB,ioBdtilovaitaeabzmaoorlrmmiaeleilc'ytoDretSe1citnedFath, Lett Bieri I Sorin i05os i WV Gel SEGeeycneeeirGahFlsioerncudbaatebiryovnadste.isosnoS,nleMdovAibameorrpsiatlailcytDoertSeicirnedPach, Late 1010 HV 2515 fEGevineetSrShaaltorrovbtastpeireovnapstn.iodnBy,ledtovNiaoromramilcietlyfDoretGerctiendFath, Left i5010 MV 6516 [GEevneSerGahtlearoavbastegirovnaess,iodnB,leNdovimaoromrabiltiatlytoDretSeicitnedPash, Late i00-10 NV 662517 R BGerneerSaL hlaotovbasteirovnasst,iaonnB,letdovaibanoorromiatlailtytDoertGecitnedFath, tate a0flo2r0ds HV es18 GE BEeveneerGGahhE laaeortovvbaastteiircovnnaesst.,ionnBB,l0o3ctoVviiAaabmOoorrrbbmiiatclaaills'yffooDrretcSeh1ciitnnedrFootchh,, FLiaocbte a50-2 i ~~ NV Gesis H EGEyoeemeGGrL hhaiaoarrcvvbaaattoiiroovnnaesst..isonaBB,ilocwddovvNiiaaoroomrrpabiiltteialtl"yftDooerrscGellciicnnedFFaatthh:, LFiedte ao50n i KV Ges [ BSGei5nn0eGSrShhaaaloetrovvvbaistteiraoovnnasst..iton8B.1i0oddwoVviiAanemSoorrrbmmiiatctaaillc'yffooDrretcSehLciitnnedrFaatchh,, FLiestkte i5oa i Vv 6571 BSGer5no0eGrOhabalsoetrovvbaastteiroovnnasst,,ionBb,lleeddMovvaiiaemooorrrmboaiilatila'ltyffoDorertecelictiienndpFaacchh,. Lbaitea aioxa Seceiicnd by dasson i WV 6622 Gsenetraleobpservation. No Abmormality Decocted o%n HV es o[enesraliabstorveatidon, wo Amermaticy Detected %oa HV G52 SGeencerriaHloeodhaobyrvadteinosno,n No Amormality Detected 8oe MV 2525 GSenierealtoebseBryvaBceiroin,o No Amormality Detected 05-2 WV 62525 GS eneraE l observaltionn, No Almormality Detected a020 ~ _-- oer Gompany Sanitized. Does not contain 15CA Gh H:24678: TwoWeekInhalationToxicity Studyin Mle Rats DuPont 8685 --~ Individual Clinical Observations and Nortality Records Sex Group Animal Observation Dave. MOVED 662527 GESeytneeerrlOaebliseereovdbastesiryovnaSsta.iiosnol,nedNovAibanGoerbmiaclailtyfoDretCelcitnedPath, Lec 01i010 WWI 662528 GESevnoerOeanlseroe vbasteirovnasst,iaonnB,ledNoviAemoOrrmbailtiatlyfDoretCelcitnedPath, Left 05i%.10 MOVIE 662525 GESeytneeerriOatblisecreovdbasteniryovnadste.isoinaB,nledNovAiamoGrembailtiatlyfDoertCelcitnedPath, Left 01i-010 MOVED 662530 GESeloneeerOlahrlaiocroevbdasteniryovnaGsta.isotnoB,nleod viAabnoorrbmiatlailtyfDoetCeLcitnedFach, Lee 02i10 MUI 662531 GES e7n0erOal blsersvhasteirovnast,ionB,ledNovAibamoorrbsiatlailtyfDoertGelcitnedPath, Left 0%i-10 MOVED 62532 GEBe7Yn0oerOObahslaeerrovvbaastteiiroovnnasst,,ionBH,leedtdovviiAaabnooorrrbbmiiattlaeilltyffpoorrecCCellciicnnedPPaacchh,, LRiegehe 0oaS-24 SlcriFicad by desion i MOVIN 662533 G7YeaonerOOabblsseerrovvbaastteiiroovnnasst.,ionBB,lleeddNovviAiabanooorrrbbmiiattlaailltyffDoorretGCellciitnnedFPaacchh,, LRiegfhct 052-2 Steriticed by seston i --~ MOVED 62534 GHEEeaeonierCShahTmlaoeosrerov,vbaastteFiirooovrnnaasspt,a,iuo,nBB,lleeBKiddolvvaiitAaaebrnaOoolrrrbbmiiattlaailltyffDoorercCcellciitnnedpPaatchh,, LRiagthet [%a= i Sechileds I Rian 3 MUI 662535 GEEevomoeOrShabclaeerrovvbaastteiiroovnnasst,.ionBB,lleeddNovviiAaamoOOrrrmbbaiilttiaalltyffDoorretcCellciitnnedpPaacthh,, tKaitnee 0a10-2 Sel dein 3 MUI 662536 GEYevanaerOOabblsseerrhvveaaettriivooanntssi,.onBB,lleeddNovviiNaamooOmrrbabiilctiaatllyffoDorretccellciitnnedPFaatthh,, LMiogthet 301-07 HHSaeiicTrrifLLioosscsee,)sFoFbyorreedlphaasrib,o,nbiBlialtaetreraall fa aee MOVIL 662537 GSeancerriaf)icoebdeobryvadtaisoino,n No Abmommalicy Detected 024.24 WUD 662538 GSeneerea nobsesryvadteisotn,a Mo Abuormality Detected 02.21 MVE 662539 GSeenceeriaflicoehds'esryvaacaisoino,n No Abmomality Detected 024.2 MOVED 662360 GSeencetriatlicoabdsebryvaatsiioan,n No Abmormality Detected 02.2 MOWED 62581 GSoimcerriatlicoebdsebryvadtaisoino,n No Abmormalicy Decected 024.24 --~ -_-- or Company Sanitized. Does not contain TSCA C8l 2 H-24678: TTowooW-WeeeekkIInnhhaallaattiioonnTTooxriicciittyy SStuuddyyiinnMMalaelReatRsas_ --~ DDuuPPoonntc8s668s5. APPENDIX E Individual Animal Blood Fluorine -- --- Company Sanilized. Does not contain TSCA CBI -- SEH246T78:TTuwoo-WWoeoskk nnbaatliuioonnTTooxxiiceiltyySSutuddyyiinnMMualleeRRaattss_ pDuupboontw.s8s66s5s --T--O--V--IDUAILNDIAVINDUAIL AMNIAMALL BBLOOLD OFLUOORDINEFLUORNE FOOTNOTES: EXPLANATORY NOTES a Insufficient sample size for accurate analysis. -- --~ or ------------ c Company Sanitized. Docs not contain TSCA CBI H-24678: Twwo-Week Inhalation Toxicity StudyinMaleRats --~ Individual Mmiral Blood Fiuerine BloodEsFollruorine BloodoowoFluorine BloodoooFsmluorine BloodDaoyFolm2u0orine Male, Grow 3 - 0 mg/m seS2e2a49923 s6522449945 1)3 13 i1e6 ia Ga2456 ii hies Male, Group 111 - 0.2 mre Sces2ass0onr ass2a5s0to0 _ pfid) sexsi pid Hate, Group V - 2 mgr sseeaass) pre if1ee4l Saeer2sszaes iade Hale, Grow VII - 20 mg/m ~ 6sse6aa2s5s3s5 ii1sss seasio 15 1i209 2 i20.0 s p1e4} is sezsin ils ie 2i1s iTe DuPont $685 ~ -Y -------------- Company Sanilized. Doesnotcontain TSCA el 24678: Tuwo-Wesk Inhalation Toxicity Study in Male Rats -- DuPont8685 --_ APPENDIX F Individual Animal Clinical Pathology Data --~ oe Company Sanitized. Does not contain-- TSCA CBI 24678: Two-Week Inhalation Toxicity Study in Male Rats --~ DuPont8685 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES GeneraAClokstg - asadmepqlueatecloceed BNENRRTC dnneoocxrs'eatamaspeelnde rorecaeoitvepderffoorrmteadsting Tw5%FRCD aTimmapamlbsel cncoootnddoivttaeilroinndi5ne for testing atviSdRuonClCHemasetaodmlmboilgeoyocvdoanldcveieltsli:oncount H5iU%r C mhheeearmnotsoclooorrnipicunscular voluns GRVHGoCHw rhFeaadainncoccloolrrppduuissscctuurlliaabrrutRHiaeomanosggiwloiondnitinhn concentration APEiD - Splhastoelluette cveotuitcutecyre Sout --_ RRAiMaoE GSGbbbiseosellluuuttteee mnTemysmstoerhyoocpchhyiele (all tome) AiAeukoees (SGbhBeoooliluulttsao beloaassriognmeonpishlnislcatned coll Sodividua) Red Blood Coll Morphology Values: AMIiSe amincirsoeccyyeeeossts nBRorLro - phedoyhlpiyoncconhcrryootmsesasssiiaa SToMmG TSacregnesthoicveiialss Wa= lRoowteloibsearlvleyd borodnyot examined; see whole blood sample condition maiviodumSaul WhitNSemoumBdalgroeodhiCceell / Platelet blood cells Morphology Values: wW5o DD vDtaoocnxudioeelabmtooedtdireoscpyhtiolpelasm BGBe CC- hpBlalasaneeeplnopirllaitcceltucemrrpissop/laessmtimate B"o1 BroitraGrheeserpvieadteioeresnot examined; see whole blood sample condition -- "102 Company Sanitized. Does not contain TSCACB! H24678: TwoWeek Inhalation Toxicity StinuMaldeRayts DuPont 8685 --~ INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES (Continued) AsmmeviTIONs: (Continued) IndiviSSdiuEfayl SerusSmeerrauucmmahlPielpmaemsmlmiyaastCshemistry Values: SANatnr D etanlaiipnamirnaetteesmniannsoitneoatncsatnasrtaosrease MA5EE5P D SsSoiarkbaliiBtionhreipndhseohstypashraotgaesneass GRSiEwoA | cCuhrroeetssatsintnioitrnraeolgen TGgiTCCT gCfleoulcotolsvepereortiediens iAobs galfobmeiminn ToWiXCD bisonetoardsgmasniiucn phosphorous FPLIPUP o spSlleaassmmyaa lhiepmessliyastsfrfornobmloboldoodsamspalmepleforforflufolruiodriedededteetremrimniantaitoinon ~~ FFieLr C- BDirsesmeas eflutornideEOD BIOS SRAC 2 ANCHE SNREES asvidWouiail OrinSvaeoiiryneeest.sflvwaolrviedse: WShheenrinTdoiasvoindsu,al81a1nimoaflwhdiactha aarree nGortplartepaoerdteidn, thite msaeyadyberdeciosrdtso:one of the following reasons or thhoovrasslasmvpalsFeasiuwnlaatsutccolcuoiltedtnetdnots(aCbroepml)SebEfaoirnetd.est(i4ng) (QNS) 5thessaanamimpzplaleiewawdsiaesdavSapoirtlioasrbuliettaobflosreuioCosrstcitoneglsltei(cnNtgSiH)on DDhoeerenidorFanonradianondnyivichdaaullafclultahotebisorenarscvoaprtedireofdnoUwraamlseuder.veictohFrodFetdhSatwaasrBpbiioleii,nrgubiiflneBsdsLaIttLeh.EaBnIRa cvaesrtarienpovraeleude,5ca0l.cu1lat0i:o0n5sAwaesrs --~ - `Company Sanitized. 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APPENDIX G Individual Animal Final Body and Organ Weights _-- 8 ompany Sanilized. Does not contain TSCA CB 8 ~3 32 3 i 8 Simmel Time 2 Po|f _BiEsIsEeErRs zExE.L | p_iiEiAsReEeSs sSeEl f Simm im LIRIIrrerrarnii|e rrr 3 Bd gimmms a fdas A fl Sm 3 i 18 gi gases BEE RgeEl oPb EpiiasEnEiscEt afsl og Ji | HTisEPoEvrRearmiilmHaat rmvermaraei BEo|g f pam pasa i Pt ooi3Elaenmnamear L|Eg ELEa : Pop a ime , BEET ED OL piE a oem Vere 4 gms Chiang i eancaiab aes |i JHmoIgE nmep wp HgEiE meaLEog diem, me 1 ee ~~ 3: ? hmsa dee 5 j oi znigmeer ssgl |dBiagEnns sny i| Polpmmun pmEg Sime simmers i Tzigess sz) 3 5iz--sa--s ng g Bi Si g 3 to EEE pmAEizRmne 1 4i Simm Eww i3 roms pied 1 lez iBEEss Bl Bp iEEEED ER B Ema mma i E: oGgenmEmlaE IaEmEmEa I ORES nus 8] Bim Rim! | iPaalibas i i 8133333 251 i i55335 35 3 BH figizemee wm) Signer nel 3 H.24678: Two Week Inhalation Toxicity Study in Male Rats DuPont $685 ~ APPENDIX H Individual Animal Pathology Data E - -- UE H24678: Two WeekInhalation Toricity Stody in Male Rats ~~ DuPon.8685 ANIVAIL NDIVP IDUA AL THOLOGYDATA KEY TO APPENDIX saston amomo: MBOiTsTsToE ipealtsholsougcyh ocTsh.anfgooessulnarmealdtetsofcsortciaabnlte,dodaficfcLfoiurssdmei,enguinonivloalttvheeerriaerlnt.s)orbip1lhaotlieonrdgaiilcc,accoohdta,er.acwtheeXrr,esedvaiepsrotirrtoiynbrusicttoiero:en:beynitd taprioct: La a1 sessed au follows: JN: wo: JoomRaT: ssvene: TThoeraansouTniemosf.chango presant barely exceeds that Which is considered to be within RInOgLeEne}ralG,oesthe lepsrioodnucies aenaysilEylncsediuomnrailcieodpabuitraofenlimited severity. The lesion Tnhietleessioanttiseproorsicnraenatm abuytstutnheerrieonis1ssipgonsisfiibclaen.t potential for increased severity. TTheIdeLgrLesYoforcheaxntgeentiteoietxhpeerctasscioemnpFliectaentasCciossnussidoeFreodrpeomssidbrlaetumocrtigorne.st enough Grades nis mrioentaioToroanltso cBthehrieonugsMhorthspeeh.voelLroeegasitecophSerevefesareecn.ttesrphirasotgsirecevssesreiofveLleeissriiovononslsv,beesietnnhgety/st4ahivysenroeistityndiaScelavoetnregs:8thceWiohrnitlseeilntauhteiWvieth --~ tens sontEucance Gross observations Listing mlciple masses for a tissue are distinguished with letters (i.e. A re ae --~ Se`ampany Sanirtorde, Poss a paral TSGACE! H24678:Two:Weck InhalationToxicity Study in MaleRats Dupont8685 ~ Sndiviaued anioad Pathology dota oroup: 1 Concentration: 0 mur sex: Males Maimal Ret `Microscopic & Nacroscopic Findings Geez TREBoepmEairnEe aarlTe Sy aRcrieficTeaHoiHntrom mcropey rons pachotony Yo MaeczoascopFioicoonnaFebem,knosrceL.aNlsiuLt,nyIioSbBnNsAOeOr,Bv1.e1dS5Te0+,hisoS,sAGsRAtRUAaSR,,ELCsheConLm.:ESGc,oomtpo.h, iB E BniEbRemiaonSea,AscRerTIimiyvoVCBoA.SsRSCILTGHSoL,3t,AB,LTER{IPSRAyANRYWThAB.GLAEGoSOpERGs,atTMoEasSa,TlE,ST,CHS, [r------ Lavenr+ ion, SUSAGITB/GHRGNIE, OL, ainisal. Yo MricreosceopieChaAEttim,eornJoabAlAei1Sc:1,ykFcS,PhiLeEePsErANv,N,eCRdESBAASOA,DR,CAaScSLPiICovCoOnRB,DE,ARPSEETCSOMTA:CH, oA rreioaAnTEP,v,aiSaShnLiDeVEn,hS.SnCPLo,RAStT,HTRYORiLEm)) aCWLBEaLoAgGo,SpEiRT,eANCTvAEESeRT,E,S, scams REE TesrEmtiIenaeLl n csarcroiticmoSaHintrom necropey Gross vatnatony Jo HEanEcrOonsCcaoptSsS,SoAaimEposr:sT,aolSiTstyoEBObaNsnoenrnevS,eLpdTEri,sHmsJ,,ANCsRAmERLaS.E, ACshoGemmoo:.s:Ccoon,u eoSEiiSEirTbmeisToneFsn.R.ASPTrveenoAsLRtDIeoSEstV,,tDB:RE2i1RSaA)TnwWeABrCoEgODaPEnGS,EDTNSEa.SiT:ET,RAE, : wissopatholony .LAGATION, SUBNGITE/CHROVE, POOR, m1 asa[ in S-- o | -- 10 WE SEicreoasE c,apicTSTAomonovre,mTaohlsiTeet,oeyvTOabhsSaSear:nRv:eAdSsGpO,rR.CEicoGoL,nh,oCsso:looSnuer,RNoiEr, RSEiRaS]nWboArnySGBEItiGsTbWHE:EAVSET,,haEEiRhOneS,sHiALDSEIe,oOmRiSSa,OgeRsS.ARPERRS,ITCLGMEoASs,kR. orcas wor moun -- TieCompanySanitized.`DoesDo%!notcontain TSCael F-24678: Two-Week InhToariclitySatudtyiniMaloeRants "DuPont 8685 ~~ Individual Anteal Pathology Data Grow: 1 Concentrations 0 m/w Sex: Males Aina Rat Wicronsopic & Macroscopic Findings Geass `EKTixelprlomesidunraolenGSDaracoyruif+ i:c1eM0ain Te La med off rom necropsy ross ratnolony + Ho MRaSEcvEroeConuTs,c,,opBIiWDcDSMSEAEoVbNSmTS,oERr,IeLCaOlNiLSGcY,EyMPTOHNAbEsNA,OReOSrR,vL,eEdSMPTL:,HEIENSP,A,NBARAEADAIRSNE,,NACLSEPCGLULNMAN,NLDSCC,OOLRODN.. FESREooCpBRuiPAALGTCuSS:N.EFRSVEAENK,IINTANULGYVREOLSLAIDRCYLGYEL,SAN,DE,YUER(ISSNN)AARAYWTINTBAHLOAIDODDPEFRGI,LCANTNDEESSR,TVEE.ST.RACHEA, EbTDIDmHiDes, STERN, HOSE Histopathology, vemELNAFrTLYaeCTHNINOGNE,, MSEUDBIMACUNTRC/LCEHFER,ONImCi,nioFaOlC.AL, mininal EPAROPATHY, CHRONIC PROGRESSIVE, mininal Yo wiE`ciLroobosss.icaonpG,EtAeRSYA,EbnAoSPrNLmEaElNiT,tLyESOR,AbLsNeF,rRvNeCSRdPELAN:SA,L CCOCRUDM.,SCTOOMLAOC,H, RECTUN, ~ oNSEoERnVSiEE,hHoRsTsLH,CYRODIDoN.nRtGLOAoNsDLe:A,RETANGAhNTsRE,YYER(OASL)DbWGOILTLAHDSGO,LPTNTIDRCSA,NCEHRSEVCAEI,NTIC EROSIATE: SEWINAL VESICLES, URINARY BLADDER, TESTES, Ertoibmdnes, STERN, NSE ssaaas ETExeiprTomTsioundarlsonGsrBaoacyurip+ti:c1eN0ain, Solna La signed ot trom nocropsy ross rasholoy + No MSaEcvtreoonsw,co,pFiIcDNUASGm,DoErNmL,aOlNiGJStE,yJURONbEIsA,eRr,vTeLdESUPML,EDIP,ANBCRRAEIANS,, CSEPICNTA.L CCOORLDO.N. SRSESETOaRCTA,aGGUSNM,BRSEPEHN,TAERRTIILNVEROLLLIDAN.REGANL,ANNODDE,EV,EP(FA)RUAWTGIH,TYHROOAIPDDTRGIELCNAANNLDESRG,VLEA,NTDRSA,CHEA, EPRNODSITADTmED:eSsT,WINSATLERVENS,ICLNEOSS,E URINARY BLADDER, TESTES. tstopachatosy var"INPLABIASEON, SUBNCUTE/CHRONIC, FOCAL, minical. No MD`iKcEOroowOsBcvDao,,picNJSARoU,mRmMaN,ElAiRTtSL,yEGHSO,PsLsEeBErANvR,eCRdEDAR:SA,IN,CCSUPMI,NACLOLCOONR,D, RSETCOTWUANC,H. SNTERSRS0VEMSRA,EGAOLTSHC.Y.ROACIDAI.REYLGLIAN/NOLDDA,ER.APTDAR,AOANFESHYY,EA(OSAL)DDRWGELINATANHLDSOG,LPAFNTIDRCSA,CNKEERSRVC,ET,ATIC EFReOtSDIiADTEI,oESSI,MISNNTLEVNES,ICLNEoSs, URINARY BLACDER, TESTES, ~~ Te Company Sanitized. Does iolcontainTSC: on54 FH24678: Two-Week Inhalation Toxicity StudyinMaleRats DuPont8685 --~ Individual Anisal Pachology Data Grow: 1 Concentration: m/e Sex: Males Raina Rot Wicroscopic & Macroscopic Findings Gaaee "EKTxTaproemsidunraelenGsDaracoryuif:+ic1eH0ain RRL hea off trom necropsy Gross pathology + Ho NaRrEgvEroeConsuT,c,,opFiNIcDBDNSIAEoYtNSmTD,oERr,IsLCaOWlGiLSStYE,yMPTNOHAEbAsN,ROeSDr,EvL,eEdSFNPLI,EMEUNPS,A,NCSRRAEADALRSYE,,RACLSEPCIGUNLMAA,NLDSCC,OOLRODN.. RESECoChBRiIOANLGTCuEs:N.EESHE,ANRTIIVONLRG)OVLELASDRICRLGYEL,SA,NDE,UYER(IF6NA)AARNWYTIHTVBHLAAODOLDPDETRGI,LCANNTDeESRS.VTEE.ST,RACHEA, EbiDIDiogs, STERN, Mosk Histopacholony LavenPLAGONTION, SURACUTR/CHRONIC, FOCAL, minieal. FRosTcAFTaLErABo+ ArToInOoNm,Y,SUmBAiCnUiTEs/.CHRONIC, minisal. No MiDEcoorvcoeDsvcMaoS,p,icCJoAEwbsIn,UorNmS,aPlLEiTEtLNy,EO,bBsANePIrANvN,eCRdESAPSI,NALCECCUONR,D,COSLTOONM,ACHR,ECTUM, ~ . SNTESRRoSVnREim:AacnUiTScU,.ROIEPDAr.NeGYLANNODDL,EA,RATPDAH,AONNHSGYY.EA(OSAL)DDREWGINLTAAHLSOL.PATYTIRSCA,CNHEERSAVC,EI,ATIC SSErNaDmA,VoESsIeCLES, URINARY DLAGOER, TESTES, BPIDIDCDES. 2s? RBBAiicEcpcaoiEcsdtueornnetLaaGlorhfloyuedpKo.sidilnlgoRe-edfdcaoyvrsee:rny24necropsy Gross pathology + No MaT"Lcirvooisn,chopFiIDcDNUEAGYbDSmE,oNrMmL,UaNlGiJStE,yNMONEbAs,NeTr,vKeLdSMPL,:ERNP,ANCSRREAATSN,. CSPRIONN. CCOORLDO.N. SREECSCIOTAMOITNAE,GGUSNW.BRSEEPNR,TAERTRIIIYVC/RLOLAIIDRNYGGYU,RDOEO,YF,E(3TP)WATRNNWUTIHSTY,HROOARPDDFRGIELCNAANLNDESRO,VLEA,ITDRSA,CHEA. EERRODSTIADGED:ESSH,ALSNTLERVENS,ICLHEOSS, URINARY BLADDER, TESTES Htstopathotony + INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, minimal. ose. `NEPHROPATHY, `DEGENERATION, CHRONIC PROGRESSIVE, mild. TRIGENINAL NERVE, 14. Ho MiRcErSos,coPpAiRcKIANmorLmAaRliKt,y oTbEsSeTrEvSed : --~ Te CompanySanitized. Does nol contain TSCA CBI H24675: Two Week InhalationToxicity StinuMaldeRyats `DuPont8685 --_~ Individual Aniral Pathology Data Group: 1 Concentration: 0 my Sex: Males Animal Ref | Wicros&Mcacoropsciopcic Pindings Geiss ETTexirpmoeisdnuarloenGSaDrcaoryuipf::ic34eRecovery Animal La signed off From necropsy ross pathology, No MaR`ciorioihs,cnopFiIOcDNOIAYbGSn,oOr,mLaONlGiSSt,Ey INOEbNAsReTr,vLeLdESCPWL:,EENP,ANCBRAEIANS,, CSoPcuIN.. CCOORLDO.N, SSSESECoTTmAOuTMAL,GCUSMM.ERSvEHRNA,TREIRTIACVRCLOIIADNRGDGL,NANODDB,EC,E(STP)AHRUAWTSIHT,YHROOALPDDTRGIELCNAANLNDESRG,VLEA.ITDRSA.CHEA. SERRIODSTTOATVEH:IDESSE,HINSATLEVMES,ICLNEOSS,E URINARY LADDER, TESTES, Histopathology 'NPLSIASION, SURMCUTE/CHRONIC, FOCAL, mintsal. Yo MiEcirrosec,opicCoAwtsm,omPaAlAiRcy OLbsAerRv,ed TESTES, N082 6209 NTTEoexirEpmeooidtsnealsoLnesGraFbociauraypihfe:+di3c4eoRefcovferroym necropsy --~ Gross rachology : No MaT"LcoErVowEsRn,co,pFiIOcDNUEAGYmDSoS,rNmNLa,UlNiGJSc,yENOELbAsReSr,v1LeEdSOPNL:,EBNP,ANCBRREAADSN,, CSRPCUIN.. CCOOLRODN.. SSRSCBoTmACiTN,IGCuSNM.EERSVEPENA:TREYRTIINGCH/COLALYRDMYPRHGYL,ANNODDE,EY,E(SPT)AHREKNWTUIHSTY,HROOALPDDTRGIELCNAANNLDESRG,VIEA,TDRSA,CHEA. EERPOtSDTAbTmEn:gsS,THISNATLERVENS,ICLREoS,s URINARY BLADDER, TESTES, Histopasholony + "INPLUSINTION, SUBACUTE/CHRONIC, FOCAL, minisal. Yo Mi`KcEriowsecros,picLUNAGbSm,orPmAaAlRity OLbsAeRrOvWe,d T:ESTES, NOSE ~ TE Gompany Sanitized. Does not contain TSCA CBI 'HL24678:TwoWesk InhalationToxicity SudyinMle Rts Dupont 3685 --~ Individual Amira) Pathology Data Grow: 1 Concentretien: 0 maw sex: Males Animal Ref `Microscopic & Macroscopic Findings Sanus refEFieimpliroerndaeecleoniosarBcoortyAipti+s3e4Recovery cross rashotony so acTCSkvhEoaisn,c,moapTtEieSaSorAcTebm,oEomrRmD,uOlNiLSSci,LyvUeONRbEMAs,ROeYDr,EvL.eodShTL,HEOSSP,A,NCDRAAEADADRSNI..ANCSoPGCEL,.ASCC:OORLDO., EEESeREiSSTBToRIEni,,TosESsRFE,,IeNsSATTLEORVALENSD,RICLsGEESoh,;ECYER(E3AA) NYWRIBOLLAGODOPRERGL,CLAATESES.TEEST,RACER, Histopacholony SirLTION, SIACUTE/CHRONIC, FOSNL, nina. evinonmy, CONC PROGRESSIVE, minisal Yo Miacsro:scoBpaicsaAnbcorenalTi,ty TOEbsSeTrSv,edSE scan ~ ETExepreomsuirene osraecurpit1i5cRecovery TRE Eiht oft from necropey prp-- Yo NaFnRcEariCossTcn,apFiVicpRnSnAomsbEac,RoorLTeEasiSL,iIeyVeIOHnbeMs,OaeDr,Sv(.eLdseHewl+,AeaSyT.,RAsANuOSa,,NECsEeGELLuNA,.NDSCC.oOLRoDN.. ESEREGbERTAr:TEo,TESRAu,nawT,ROVaEISSIC,LGENS,DB,UER(IP8NA)ANRTYWHIIBTRLHOALDODDPEERSL,CLATNDEEERSV.TES:T,RACHEA, torus, STERN, Whe niasopatalony SATLAGICION, SURACUTE/CRGNIE, FOAL, minis 0 wiacro,scopicCoavpea.ormTaAliReyRoAbse,rved TESTES, O53 ~~ Te CompanySaniized.Doesnotcontain TSCA CB! FL24678:Tuo Week Inhalation Toxicity Study inMleRats DuPoni8685 ~ Sngividual animal sachology Daca Group: 111 concentration: 0.2 o/e _Sexs_ ales minal Ref | Wieroscopic i Macroscopic Pindings eau `SPTerepiromvriyuncalecossraocurtipfi]+ceHain Sonar ta sighed off trom necropsy Gross patholeny Yo NaFAvcazinoRsnc,opFiBAcDSToEAcSbEba,RaorLimT,EaINlGiLTStOE)yNAERHObSEsN,Neor,tvS,eLdSEOP,LAESSNP,,RWCBRAREADADSNR,,ELSCHPGEILLNNA..DSCC:OOLRODN, FESErOoRhEAnNGCUES,J,ESRERM,AIRNTALHRVOLELASRDIYOILGLSL,SA,NDT,UYREI(PN9AA)RRKYW.IINTBYHLRAOGOLDPDETRGE,LCANTNDEESSS,TEE:ST.RACHEA, Ee oromioss, STEM, Most nsstopatholosy + LAPLAMATION, SUBACUTE/CHRONTC, FOGAL, minisal. "NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. 30 Miicorsos,copPiicaRorAeRalIi,y SobEsEerSv,ed0s cease ~ TEieirpmorisnuacrle sazaoctrpificasteH]ain fee -- Gross pachotogy Yo NSRaovsEoeznCoa,aTcroFpBicSDovEcAMeobER,miEuoRNrLL,rEoawlLSsiO,EyNIEToNEbAsN,ReoYrk,vT.eLdESOTPNL+H,EURSP,A,REEAAALSS,K,ERCSEPGCILHGA,AIDCCSOOLRODN, EESRESOESDAPTTuAAATGGEu,HSESRTEmH,NAATALIVRHVOEILSIDECLG,ELSA,DE,RYIEGEMAARNYWTIITVSHALOACIOEDPEIRGS,LCAYTNDEESSR,TVEES,T,RACHEA: Ertorbtioes, STEN, NOSE Hscopatholony + `pLaaTION, SUBCUTE/CHRONIC, FOCAL, miniral Yo MiEcraorsc,opicLoNAGbSn:ormPalAitRyLObIseNrv,ed TESTES, NOSE ~~ 140 pany Sanitized. Doss not contain TSCA CBI 24675:Two Weck Inhalation Toxicity StudyinMaleRats DuPon: $685 --~ Sndivicusl Anisml Pathology Data Group: 13% Concentration: 0.2 sa/m Sex: Wales Animal nai | Wieroscopic & acroscopic Findings 66209 `ERDixeTprTomemidunreleonGsDaracoruyip+fi+c1eM0ain - Eo a oned oft trom necropsy ross atholony No MaRRicEmriCaosT,cc,opRiWicDEDNSoEAEYgbNSmFo,oEnrReLL,aSOlWiSLScYE,yNRPNYMOMEb,AsNROeEOr,EvL,eEdSTNPL:,NEESNP,,ANCBRAREDAARDSE,,NACLSPEGICLNAA,NLDSCC.OOLRODN.. SSFCROIORSRTTALATCE,:NERSVFIERM,AINNITNAHLNY/VRLEOASTRIDNCGLGEEL,SA,NDE,YUER(IPENA)ARRNYWTIHTBRHLOAIDODDPEFRGI,LCANTNDEESRS,VTEE.ST.RACHEA, Hibibwiogs, Sree, Host Histopathology + "INPLNSUATION, SUBACUTE/CHRONIC, FOCAL, minizal. Yo MiKcEErNoEsvceo,picLUNAGbSn.ormPaAlAiRtyO/OLbsAeRrAve,d T:ESTES, NOSE e250 KeTEirxTompiioaensdee)soLnasGarFbcoaaruymipef::dic1eN0oafitntrom necropsy --~ Gross vatholoay + No Ma"ScToErVmoAsa,c,opKiIDcDUGEAYDbSeE,oMmmL,OaNlGiJSt,By NONbE,sNeTr,v1eLdSEPML,ESNP,ANCBRREAALSN,, CSEPCIUNNA.L CCOORLDO.N. _RSEESESOApCTA,HGGOSWN,EBRSVPEETA,ERRTTIAYCVRLOLETANDGRHG,LANNODDB,EY,2(E5TA)HKOHUNISENT,VHROOALPDDTRGIECNLAANLESRG,VLEA,NTDRSA.CHER, EFRrOtSoIbATiEi,ogSsI,HINSATLEVRENS,ICLoESs, URINARY BLADDER, TESTES, Histopathology : rose isso. NPLADORION, SUBACUTE/CHRONEC, minimal. No MiKcErEoNscEo,picLUNAGiSm,ormPaHliAtRy)obXseRrv,ed TESTES orcarsuyeor ExRIED: --_ Tr "SompanySanitized.Doesnotconlain TSCA CBI 12F4E26476788:: TTwwoo-WWeeeskkIInnhhaallaattiioonn TTooxuiicciityySSodytiinnMuMaalldeeRRaayttss DuDfupoonn#t866s8s5 --~ Individual Ansel Facholosy Beta Grow: Tx Concemtration: 0.2 m/e Sex: Males nica rat [---- Ey SBRSaiRgmeoiRsnieaslensoarTecerlipRf+ic1ea0otientrom necrepey Gross patrelons Yo NaoSEcvhEsaoiTts:mc,oapTsiBmeSSnoaAEriosmE,opRr,mDGaovleiSLsc,EyiAONbERAsMRoeYvr,sv{.eLdSoPTLD:HEEENE,,RRARADEOVN,SNECSHGYELNDAGDSCC.OOLRO)N, SSEREEOTSETTEARGRAE,T,ESRFEHA,MsAILNVAEORSIIRCSLE,GS,;BYUERIP(3NA)AAANWYTREBAAODLOGDEPREC,CLNTSEE,SRTVEES,T.OACHEA: EribTomioss, STE, Nosh wistopathelony `TAELNGITION, SURACUTR/CIRONTC, ROOK, minimal Ho MiEcroescopicCuNeim,orsTaAliRcyRoLbsaarv,ed T+ESTES, 105% cesor sBBReresRsotareesatadoGrtrSyoEdu5xoRpisetti+inogRodedFcaovvEeev:reyn20neceopey ~ ross: macnotony 0 WaahScEukrConssTic,o,pFsiBncbSuToibRrssT,ooERmoKC,o:zweTLeseyiE,vAiOWMbERs,RKeoErt,1v,eSSdTPT:L,HEIENSP,A,RAEALARYSE,,ALCSPaGIcLNN,.DSCC,OoNlDo., SEEERSREoboEsmttiRbAn:TmcRoi,sYo,roSsne,,NASATLTAEACRVRENKSI,SICGLGwE,eSud,,$1U2R(CP8NA)ANATWYHIITBRHLOALOGODPEERSL,CLNTEREOR,TVEES,T.CHER. cease DTEopreomttduzret)onsobarecayeuspsi+c54eRacovery . RRL CER OFF trek nocrepey Gross Bathotosy Mo NRaoCcOhcTnoiOsmc:oapFsWAcpBVSoAAEmcT,oEorR,mLLa:olviGSLSco,yEveAOnNbEMsNNaoTro,vL,eodSoPTnL,OEESNH,,EBNAASARDE,,ALCSPaGINNLA,ALDCC:OORLDO:N. SEEREOBASRTELATCRE,TMaSPuIe,IkNAiTLHnYRVAEOSIRIDCLG,ELSA,DB,U1R8IAN)TARRwYURiBOLALOGDOPRERG,CLRITNDEESSR,TVEES,T,RACHEA, ERiStbovioss, STERN, Mosh Tia Company Saniized. Does not contain TSCACBI F-24678: Two:Week Inhalation ToxicityStudy in MaleRats DuPont 8685 ~ Individual Aninal Pathology Date Grow: Tri Concentration: 0.2 mpm Sex: Males Anima fof Microscopic & Macroscopic Findings Gass ET`TxieproemsidunraleonGSDaracoyruipf+ i:c3eR0ecovery nfm La signed off from necropsy axons pathology, No MaSEcvrEoaOsc,opFiIcDDMUAVmSDo,Srm,LaolNiGSStE,yIUONNbEAAs,ReSr,v[eLdESDPNL:,ERNP,RICSRNEAALSN., CSEPCIUNMA.L CCOOLRODN.. SSRCEEIPCRaOTNMLG,CUSWN,EESRHFSNE,IAERRTIIHIEYGR/OLILYDANRGGYL,AONODEF,Y,ESSTA)RHNUWTISHTN,HROOALPDRFEGILCAALNNDESRG,VLEA,TDR,IER, EPRoOiSbTAmTiEn:aSsI,VINSATLERVENS,ICLNEOSS,E URINARY BLADDER, TESTES, as2s0s iTEeTxripmoeisdnealsonsGraDocaurypit+ic54eRecovery Ena o lame of tron necropsy ross asholoy + No MaT"Lciorvionws,cnopFiIDcDNoIAGVbSDn,NorNmL,UaNlGiJStE,yTAHONEbAAsR,eTr,vIeLdSEPDL:,ESNF,RNCBRREAALSN,, CSPBICN,. CCOOLRODN., RESEoECmuOAANTG,uSVF.BRSIP,NATREITRIOC LCDAIDRNYPGYHuE,NnO,DEEY,E(s6Ta)HiUWvSIiT,HolOAsDPRTESINCoALsG,LTAINER,aDS.ta ~ ESRDOSoTmATnE,esS,HINSATLERVENS,ICLNEoSs,h URINARY BLADDER, TESTES, se2506 TEKeixrTpmToiosndealsonGsrDaoucyuripf+ i: c30eRecovery inal a signed oc fron necropsy ross ratnolony + No MaSicEiroaous,cCo,pFiicDuUvAGabDn,RoIrNmL,UaNlGiSSt,Ey AWOEbTAsReTr,vLeLdSEPDL,EDNP,ANCSRREAALSN,, CSPCIUNMA,L CCOOLRODN., SSRCEOICNDOTMAL,CSNM,EBRSFVSEEMA,RREYRTALHGEVROLATIRNDIGHGD,ANDODB,EY.EPSTA)RHKOWISVIV,TROOALPDDTRGIELCAANLNDESRG,VLEA,TDRSC,HER, EPrROiSbTtAbTvEi,oeSsI,MISNNTLEVNES,ICLHESSE, RINARY BLADDER, TESTES, 1a erapany Sanilized, Does not conTtSaCAiCEnL H24678:TwoWeekInhaloton Toxicity SudyinMaleRats DuPont868s ~~ Individual anioat Pechology Data Groups V Concentration: 2 mgm Sex: Males Aniral Rot "Microscopic & Macroscopic Findings asia SemiREEanTEtaEelSr scaSoocninryRieef:dic1eU0nEa"tntrem mocrapey ross sathotosy No MaaErceroEsnscopRiVocBRuStNIuebTm,RoA,rLLaSMliTSLcI,yMaPGJbnEs30e,0rkvi.odcsTrei:sRayP:.ANpCARaACmSR,,E,CsHeOEmNL.,N,CcoOnLdO.N, SREEEtOiAeGESN:ESFRAe,dTsITNAvVRBbASILDRCiG,aLsa,VDP:TEERLLSENA)AARYANEIBHHLAOGOLOPEERG,CEANTOEESRS,VTEE,ST,RACHEA, Sibrioss, Stee, oth nssecpocolony + wee Ciecaanion, SmcUTECONC, Dirieotion, SAUTER, FOCAL, nine sinieel. 10 MricroescopicmsAp.morFoRaAlity ObasRerved TESTES ssases eEframmriensercsoaeucpe'i]:icnHain --~ ERE Ciomot off rom necropsy ross satnotosy No MTaCochvreoemesncoonpTYiicSBOrSoAEepbTE,mEioRcrhLTm,GaGlSSiLc,yrEUObRsNEoeorkvG:eLdSETNiH:SOP,SANCsRNaEmARySE,, LSSoGPLcACNDSCC,OORLDO,N RSSEOoTEr:,aNESFERAHRERAVCSEAESRDSEILBSv),DB,C1RIP8RRAARAwYTmBAOALOGSPOEG,LLANTNDEESSA,TRE,ST,RACE, Erioimiots, sre, ost Hissopatholony `INFLAMMATION, SUBMCUTE/CHRONIC, FOCAL, minimal. AS akapiASTn, mins Ho MiScroTscopicCaNm,ormThaeloisy. obVsoesrved -- Tae Company Sanitized. Does not contain TSCA GF) 24678: Two-WeekInhalationToicit Study in MaleRats DuPont $685 ~ Indsvidual Anical Pathology Data Groups v Concentration: 2 mg/m Sex: Males Sninal Ref| Wierascopic & Macroscopic Findings Gas TEfxopmoisrunreeeGsarcot rwif:ic)eHan La hea oft xem necropsy ross rasholony + No NaSEgvoreomns,aco,pBIiDcDNoIAVbDSm,oIr,sLaOlGiJStE,yTNWObENsR,eTr,vLeEdSMP,LEP,AWCSRWEAALSN,, CSEPCIONMA,L CCOOLRODN.. RESoEErACiLA,GEySNW.EBRSPVEEENA,TKEITRNUIGVC/RLOLALYRDWIERGHYL,ANNODDE,EV,E(SSTN)UANMWTIIHSTV,HROOALPDDFRGIELCNAANLNDESGR.LVAE,NTDRSA,CHEA, EFRROTSDIIAToEm:DRSSE,NINSATLERVENS,ICLMESS,E URINARY BLADDER, TESTES. Histopathatony PH"ISNAaLAUNOORUUSTIMOE+NT,APLSAUSBTAAC,UTEm/iCnHiRrOaNlIC, FOCAL, mintnal No MIicNrEovsceo,picLNACbSn,orTmEaSlTiEtSy,obNsOSeErved sass TEEexiprTomesidinc)oenGsBraacoyruipt+:ic3e0Main --~ onan a Sanaa oft zon naczopsy Gross rashelony No NSEaTcvOriMoAsaCcHo,pFIiDcOUGEAYDbSmE,oNrsL,UaNlGiJStE,yNNONEbAs,ReSr,vILeEdSUPML:,EENP,ANCBRREAALSN,, SCPECIUNN., CCOORLODN, BSRSCEOICPNATRAL,GEOSNM,EERSVEFENR,TAERRNIIIVGCR/OLLLAYDRNAGL,ANNODDE,EY,E(PSTA)RHAIWTNIHSTY,HROOAIPDDTRGIELCNAANNLDESRG,VIEN,TDRSA,CHER. EFRDOiSIbAmTEo,gsSI,MINSATLERVENS,ICLNEoS,s URDNARY BLADDER, TESTES Hsetopathotogy 1 LiPLABIATION, SUBMCUTE/CHRONIC, FOCAL, mintpal. ars SNGQFULIMAROOUPASTHMYE,TAPCLHARSOINAI,C FROGRESSIVE, minipal. minimal. No Mi"Ucornocss,copFRiScTEASb,norMmSaElity Observed ~~ 1a CompanySanilizad. Docsnotcontain TSCACE: H2244667788::TTuwoo WWeeeekk IInhnahlaatlioanTtTooiiioscntlyySSudtyiinnuMMauldeeRRaayttss DDuuPpoonntt#668853 --_~ Individual Animal Facholosy ata Grow: u Concentration: 2 raw Sex: Males Animal Ref Wicroacopic & Macroscopic Findings Geasie `EETTrheaRmetiraInaarleoTnoSHrpaoacuyrhpi'efd+ic0eoHaeintrom necropsy Gross pathelons Ho NaTCTczhEkoisCehopEtYAcDRDoSAoISipTc,eRoiArNLmL,SaolwiJLavo,RyveAoNb,EsoeNrovEeLdSTEP,EURE,SRNCBRAAESDARNSE,.OLCSEPCCRLA:LDECC:oOlRaD, SESREOSEUPILNRGESA,MonSgFeRB,A MDAAYRRVEONSIIDGCLG,ELSA,DP,LCBRIEE3NA)AARRYWHIVBREAODLOGDPETRGI,CLATNESESR:TVEEST,RACHEA, Thiblomwioss, STEM, wos natopatnoiony wwaonveesn,LIAireLLAAMSAICTIIOONN,,SUSUBRAACCUUTTRE/CCHHRROONNIICC,, OCNL, iniral. inisal. ru TAas YeTAPLASTA, minisal I i Tabras,-- ost --~ seas? ETEEeirpmRRoirneacleLasraHocoetiht|:eic5eoefccovferroyn necropey Gross sathelony saasio ross Sricowomeion, bass, vorTLED. so aTEceEzoeonis:cno,pMtEoeSiSorAcbSemo,oEmrCmD,aMlTssLc)ReyAhOWNbasN,rOeDr,EvT,eLdSAPEDL+ REmIP.AANNCSRGAELIAANSS,,S.CSHPSICLNI..NFCCLOCORLDO., SEESEReEOtiSsoRT,mARRiERoA,tGeSp,mDiitpshGnanLnAaVDEA,,SRIeCEvLwAtEUo,SNs,TEIYUYERR(IOSLN)DARGWYLAEBNLDASGS.OFEERTL,RCACNTHEEESRATV,EES,, rE Sp exmpmoirnuT ar cde GsraE ocy uepiticeRGecEovEerRy necropey patholosy Ho NaSEocvhEzeCConhsT:ea,o,pPWsoReDiSioASrbNesaR,oEsRr,LmSGaolsSiLt,IEyNTEWOAbaNs,AGemnr,GvC,eLSdTEeH:eImNP.SA,RpAAARS,E,ALSCHPGULINA.,NDSCC,OORLDO.N, ERSiEEIETATTREG,SEnSephi:uAnmTaHUVRAEOSLRKDCILCELLSO,WEDY,RELPA(5AA)ARAYITRTBTHLAAODOLDPDEFRCL,CLATNDEEES.RTE,ST.RACHEA. ERiEibiots, eon, WS --~ "146 mpany Sanilized. Does nol contain TSCACB! H24678:Two-WeekInhalation Toxicity StudyinMaleRats DuPont36% --~ Individual antral Pathology Data Grow: Vv Concentration: 2 mm Sex: Males Sina Rol Microscopic & Wacroseople Findings Gass EKTxeipxiomTmieundraelonGSarbcouryu:ipfi+c3eR1ecovery Foal {a Fined off fram necropsy ross Pathology, ssmpiDoEnSiCDOsLOsNNTION, TAN, LEFT, TALL, IW DIN. No MaSvceronons,cnopRIiocDNUEAOVbDSnR,oIrNmL,aONlGiSStE,yIWONEbAs,VeEr,vIeLGdEPL,ERNP,RICSRRAELANS,. CSEPCIUNNA.L CCOORLDO.N, SSRCSEEoCRmTTAI,GCUSNM.EESRTIVRF,AERRTTLHISVGR/OLCTYADMRPIGHKL,ANNODEE,Y,B(BSTA)HAONWTRIISTV,HROOALDPDRTEIGLRCAANNLDESRG.VLED.TRSA.CHEA. SEReoSmIiAG,S.NoSsEEATNAL VESICLES, URINARY BLADDER, TESTES, seas20 TEToxrpeaoisdnuarleonsGrbaoucuyrpi:+fic30eRecovery AER La Ciohed off From necropsy Gross racholony No MaTEcvroeonns,c,opRiIcoOyGRAYbDSnE,oNrmN,aGlSiJt)EyAOWNEbNs,ReTr,v{eLdSEPLN:EENP,RICBRRAEIANS,, CSEPCIUNNA,L CCOOLRODN.. ~~ ECSSCTORORIA,LGUSNM,EERSVEENP,THEARTIRACVIRNOLLIIADNRGGYL,ANNOBDD,YEE(P5TA)KHTOWHISVT,RHOLAODDPRTEGINCLARNLDESRG.VLAEN,TDRSA,CHEA, EERPODSIIADTIED,ESSm,INSATLERVNENS,ICLHEOSS,E URINARY BLADDER, TESTES. wos ToEFeixralpmloitesnduarleLoansGsraDaoacnytripet+di:c34eoRfetcovferroyn necopsy Gross vacholeay + No MaCLciovrueonns,cco,pRiIcDEoASbD,oIrs,TaOlNiGJStE,yOONNEbAs,KeFr,vLeEdSMPL,EENP,ANCBRRAEIANS,, CSPBINNA,L CCOOLRODN.. RSSSCEoECmRNiTAL,GCUSNS.EERNFST,REARTRLHEIYRAOUCIGDAHRGL,NAONDDEE,Y.E(PSTA)RHAUWTISHTY,HROOAIPDDTRIGELCRAAYNLDESRG,VLEA,TDRSA,CHEA. EEReODSTiAoTSo:esSI,IMSNTLERVENS,ICL0EsSt, URINARY BLADDER, TESTES -- Ts `Company Saniized. Does not contain TSCA CE! F-24678: Two Week Inhalation Toxicity Study inMaleRats "DuPont8685 ~ Individual Anisal Pathology Data Group: vir Concentration: 20 mam Sex: ales Animal Rot Microscopie i Macroscopic Findings Geasar | TAEKeixlmTpmeToiesanduarleoLnasGarsDcoiaruayipnfe+:idc1eN0oaftfa,trom or necropsy o Gross pathology + No MaRvceornoas:nco,pBiIcDDAoSo,Drm,aClONiSGtSEyNWONbEs,NeAr,vLeEdCNL,E,PAWCBAREAAISN,, CSHPIUNMA.L CCOOLRODN.. SSRCE0ICPROATNGL,OCSMN,EBRSVFIERT,AERRITIRVGGRUOLLIAYRDMIPNHGEL,ANNODDE,EY,B(PSTA)ERANWTDIHSTN,HROOAIPDRTEGILCAALINDESRL,VAED,TSRA.CER. EFRROTSbItAbTHEi,oeSsI,MISNATLERVENS,ICLKEoSt, URINARY BLADDER, TESTES, Hissopatiolony Pcrvriss wasNIENPPHLRUOOPOATTIHOYN,, CHSRUOBNAICCUTEP/RCOHGAROENSISCI,VE,mimniinmiamla.l. PARITRAORNS WE+TAPLASTA, 1d. ~~ No MiSEcRroRots,caopSiPcLLEEmANMb.m,orBmPAaALlMRi,EtRySSOP,bIsNeCArLEvNCe,dOR,COLSOTNO,MACRHE,CTD,IOWDEES.HTERIC Tough Nook, THORS, ADREIAL GLAS, SCIACIC NERVE, FOLD SEErTkaeI,s.RPVEARrRI,AbTiAbPRIROMOILSoDERASTG,EL,ANSDSTSEE,IRNTNAR,ALCHNVEEORSS,IECLBESSO,PAUGRUISN,ARYE.YEL(ASD)DEWRI,TH onahvseor svn: -- THs Company Sanitized, Does notcontein Ts:cACl 1124675: To WecknhlationToxicity StudyinMale Rats Dupont.8685 ~ Individunt seed Fatholosy Daca oroup: iT concentration: 20 mare sexs ales Sima Far Nicrasaepic & Tacroscopie Findings case SESPaerrpmaiivLnivaeleysaaRrcreeif'diceaHseoron meron cross achotony io HTaEeEcsnoescopFieicereaetm,orsmmTatsiST,cyIEoWbsWReorovSsedLsTrEeUeS,ShCmRAiaAnRS,E, ,tsoCnnLoA.DSCc:OoLmO, E ERRiOsEtTehiAotSs,IaSsTAnALeoRmRAr.RGCL,oCRSvk,,BTrRePaIANNwIeRGrAESoODrEnRGi,cataToEssSi,TaE:ST,ACHA. ssatopacholony w. antiLsiopRioemArTnIoOsNt,s,SRBATUET/CIIR,ONwC,d.TOOK, mnie] e roTiha einar nmo0sa,saw.i Wo NiecrCascopEiac temoSrsraaismeyaocbyse,rvSedri coro, sow ~~ Ei DSUnOrDEmENiUcRMAt,:bEJiEBEJnUrDINiURSMv,bsESoI,tRL,ETUPMTO,AIVTsPTCAHSNoCTORnEEALAsOSR,RCaNiCPn.sERCeOeULS.NT,,ARTTERBC::AOpCLrHONEoS,An,IcRAoEsCCTsU,M, --~ Te ompany Saniized. Doss oto-- tal -- H:24678: Two-Week Inhalation Toxicity Studyin Male Rats DuPont 8685 ~ Individual Animal Pathology Data Group: vir Concentration: 20 mg/m Sex: vales Animal Ref | Microscopic & Macroscopic Findings Pera TTEexropmaidsncaelonSGDrauocuyrpif+i: c1M0eain Eat Le signed off `trom necropsy Gross ratholony + No NaSvcheronows,cno.pRiIcoDNUEAOvDmSEo,NmUmMLa,UlNiJGtESySURONbEMsA,eRr,vTeLdSEPL,:EENP,RICBRREAAISN,, CSEPCIUNMA,L CCOORLDO.N, ESRSECOCEbiTNA,EGuSNN.EERSVPIEHT,AERNTIIH/GYLRAOYRIDIWNGGL,NANODOS,EY,E(P5TA)ONTEWHSIYT,AHOAIODDPRTEGIVCLAANLDESRL,VAED,TRSA,CHEA, BrRiobDiTbACiEi:ngSsI,MINSAeL oVE,GICLNEoSs,e URINARY BLADDER, TESTES. Histopathology. APLNOTION, SUBMCUTS/CIRONIE, FOCAL, minisal. AR SAOPULARUIRBOIUTSIWOE+NT,APLSAUSBTAAC,UTEm/iCnHtRpOaNlI.C, minisal No MBoicivrceoorsncsoe,p,icHSEARAboTmv,ohromSnaPLlEiKEtNyn.,ObBRsAeDDrYav,eadSsY,INALChCoORoD,CSSTOOMACHt,hera, ~ SSSoOrRiMkAcuTsVY,ERSGIBLCYDLBE(GSSL,)ANUWDRI:IRNPAAROIYPNLTBLALCVARDNOOEELRRVD,E,GTLEAPSNRTDOESSS,T,ATTERE.APCIHDEIAD,YNIDES, Seen, wos TTs0- `CompanySanitized.Doesnolcontain TSCA CF. H24678:TwoWeekInhalation Toxciy SudyinMaleRats ______ DuPonciEs _ } Individual nnsoat Pethelogy Data Grows VII Comemmtravions 20 maser sex: Wales prey Tiaroreopia & Nackoscpie Findings Cease eErrmbiinienacreriti]+csvain RE Time ob trom neceepey Gross patnatony + wovensiscoiomsan, Ta, worneeD. Yo NaRmEgerooiescooc,picuEnaTeTie,mNeo:rBoOmAniRSetS,,yLiTOSbRsreTSrAAv,NeCRdEOBRRRDA,IAN,CLoSeGPnIL,NAASLCO,LCOONSO,E,IARSEFTCLOTCMOARC,H, ERrrOeETAvASBLEAIUADLNIGALLVA,ESLc,TLASTS.ITETIARRGL(LA3)DANYWGELBPAASGoS,PEERTL,CRATNCEEERSRVT:EE,S, Sion, orien, Most [r---- riipLRareoasriieon,, sSiInBACSUoTrB,/CImRiGnNiImCa,l Fock, aiasrel FI -------- rLoBTION, SUBAGTE/CIRONIC, nnisal ~~ - esurnassa ]hTaWHoitR AnoRmooamrEnTyLN,EARSsViEEn,sea2l0.14 J AArsieeaanE Nor FRESE mn cat, pens, mild 0 MiE OHcrEoEscoe pibcatNihmSorSomPh anlRinLcyrGCoonbWds,e,rvaSTeOdSMeEALCNHT,EtRDUWhEOADVRrEN,N,TeHSREoOTEAS)CG,LAND, wERovnea,batwDoisCLASS, hSaNRT,RSLeELResO,RAROESARESYRLLSA)DDHELRT,H SOEPSTTIECS, --~ i Gompany Sanitized. Does Rot contain TCRoe. 24678: TwoWeek Inhalation Toxicity Study inMaleRats Dupont8685 ~ Indiviu anisal Pathology bata Grow vir consmeravion: 20 mar sex: ales Amina sot Niaroseopis & Naczorcople Findings Ga TeE eruzirnael S osarcrpificemain REILTIRA GE trom nacrepey Gross pathology Jo MaFE cIroCsc.opa iDcuAObmnoIrmTalSiJTachcyuunODtbonesa,eonresvSe1dsTe5einsnT,A,CmRRaEnREyS,,OSsoocSomDmo,SG:cootrooh,, E TBiSTbErions,EwoSrrAiroioRt,isIoC,sLtAP,iPeR{Fb3)RAARTYWIeAFrAGGLOhDPEnRGi,CLAhTSEaS,iTE.SA.CHE, Histopathology Limuneeion, SCT/CIRONC, TOCA, mine. Cisoromom, minimal ras]LaeWeeETsaOwPmhEReoMsFEaRFEr,esem:ite ~~ Jo Mif Ecraesconie sunmAabsne,ormSoPaLlkEiEt.Ny.oSbWHsAeHTrv,eedAsObNiEcGomL,ASos.tyoBErT,ATLC EaETceTrCDyLRSSCuCWehiuAaOnRhAASSELAAMADES,aGTRNEDRS:E,TEEAPCOHIEOR,NIOES, saasrz RER J adEesy LelI5SRucEoveHry necropsy Gross pathology Jo TMaf i EcroscopTSiii camarATebEm,oRrLeLsaSlimo ,tyhOJbBYAsNoee eor,hv.edSTizHeO,o SsAuvR.g BsoGLmAaNDSc,on. SR nmTS its,AmSiiveonViAnnsRLeILSvsos,sLBiReFi3XRnEWIETBAEOnLODPe,GSEIGTaSEi.SeTHEACER, Hiasopatbatony Sirinention, SECTOR, ROCA, mines] o MicroscopicCuNeo,rmaPlAiRtyROCbsxerv,ed Tesres, ose -- ee Company Saniized4.- Doss not contain TSCACE! -- Individual aieat Pchology Data croup: vii Comomracions 30 sure sexs Males Animal Ref Geass | Microscopic & Macroscopic Findings FEocmsienaLl Sacsitice EToI re sScEoHrRe neceepey Gross pushotony snesis couomstion, RED, sexTERSD. wo MaCcrEoscopEic eAmoTErEANmiRvSay, a ose. OSibhsnieErSR,vmxeidaSahdOa,aR,CEasSlpeoosvcooS,nE,TRNTsEEoCCwT, a ESaoroTe.tN aSemes nA,ratbas:nikScmLihEas)ansGHohanseeS.ePkSC, TREoOvE. [r-- ipieTION, SUVACUTB/GIRGNIE, FORAL, minisal [ER Ee CS Ta-- a, fess, vost case ~ TffLeerraEniesAaSecrieteiorn-- ge g-- Gross achotony J E EEEERISES OSST,ONUiC-- EokA.SSatAnDaS,EaisaAmtaaRs,E, AsShpGeomnD,.SCc:oorvo,. ET BE otaesSninhoeteis, asouo,hk,BAodFnhAswSeBrToAemrr,GsLAMTEaSan.riEsS,T,RACHEA asepachotony + \o MiAcSrToEsRcopic AmoTOrNSy) Scaharsarvnedva1 se, caorss, vos -- ~153- `Gompany Sanized. Does aconISCAGE! $24678: TwoWeekInhlaion TricityStdy in Mle Rats Dupont --~ Cndtvidunt Anioal Pchotoqy Daca Go viz eisai sai consentracions 20 mim sex: Wales Wiceescople & Weospis Findings = SFDSeecoaniprneaalsysacrieficeFMhaEcoHweLey cecroney Gronn pashotony Jo MacsosecoopA is NorY mality seerrvuedSeed anS,oahmnan,, Cshpeumn:. cCOoLmO, SEDC. PODrEoReaTaosvua ,,ioBni".miAsan)otseoerBoOcAooreResG,sLEATSSeoCo.srLeeAsT,RSA:CHEA, ote Shin Jock fr-- als-- SE ---- - Jo WiDRcErGEEoNsEcRoRApTiiIcsONAe,mnoTrCRmIawGtEiM,tIyNAScLhENaREeRRrEVvEe,d mild. --~ saasse sTEerEsienat A sTaceridfice-- SEHR necropey aroun Pashotony to MaScrTosOcopiRcenIinmGoorsimSUtiysoicWcobAnNa,RsorDov1ke1SdA0heA0,MttHaIh,,oAcOmtRJaaDcayRgG.,LEACshSoeG,omLn.:ATRSACc.CooHLrEooA.h,, BEThole:wSohuSAtnReGos,a,tBRinioay nwiBmAsootny, TESTES fr-- rxaamnetE( svimoT rsi,-- co-- x mRo-- cRESsI-- vS, mi-- nieal.-- Jo WiRcroEscopBisaNnoarmnalai,ty dShRsesrrEvSede-se --~ -- eee--e--r----pe---- BER----om-- pany--ani-- zed-- Dossn-- e co-- nan TSCACE!