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ARA%6 _ 3282 464 AR2AG - BREA _ -- --------_ Duro-- n 11414 `TRADE SECRET Study Title H-25134: Four-Week Inhalation Toxicity Study in Male Rats TEST GUIDELINES: OECD Guideline for the Testing of Chemicals Section 4: Health Effects, Number 412 (1981) AUTHOR: Linda A. Malley, Ph.D, D.AB.T. STUDY COMPLETED ON: June 25, 2003 PERFORMING LABORATORY: E.L du Pontde Nemours and Company ~~ Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 LABORATORY PROJECT ID: DuPont-11414 Company Sanitaed. Doss na contain TSCACE! -- ew B2235113344::FFoouurWWeeeekkIInnhhaallautioonnTTooxxiicciittyy SSttuddyyiinnMialleeRRaatss -- DDuubPeomncti1i14d1i4e GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT LTahbiosrsattuodryywParasctciocneduSctatneddaridnsc,omwphliicahnacreewciotnhsiUs.tSe.ntEwPiAthTtSheCOAE(C40DCPFriRncpiaprltes7o92f)GGoooodd `LGaoboodraLtaobroyrPartaocrtyicPera(catsicreevSitsaenddianrd1s99(75)9 pNuobhlSisahnedNoi.n E3N85V0/)MeCx/cCepHtEfMo(r 9th8e)i1t7emadnodcMumAeFntFedJ.apan below. The item listed does not impact the validityofthe study. ``uTnhdeesrpGoonsoodrLcahbaorraactteorriyzePrdatchteicteesSttsaunbdsatradnsc,e.botAhltthhoeuvgahlitdhietycahanrdacatcecruirzaactyioonftwhaesannaotlypseirsfworamsed considered acceptable and therefore sufficient for the purposeofthis study. Applicant/ Sponsor: E.L du Pontde Nemours and Company Wilmington, Delaware 19898 USA. --~ StodyDivtor. __Zgey 2 Pal LiSnednaioAr.RMeaslelaeryc,hPThoDxi,coDloAgiBst. 25 Fae --aas Applicant (Sponsor __________ "DuPont Representative Date Company Sanitzed. Doosnotcontain TSCA car ~~ -- er TT---- --eeeeesoeseeeee 2$:2251%34: FFoouurW-Weeeekk IInnhballaatioonnTTooxiiccittyy SSudtyiiunnMdMaallyeeRRaatss _ -- QUALITY ASSURANCE STATEMENT puDurPonwtt-1n1a4i14s Haskell Sample Number(s): 25134 Dates of Inspections: Protocol: September 20, 2002; October 7, 2002 Conduct: October 14,15, 2002; November 1, 2002 Records, Reports: FMeabyru2a7r-y303,,62,02063-;28J,u2n0e031,;2M0a0r3ch 20,21,24, 2003; April 7, 2003; Dates Findings Reported to: ~ Study Director: 5S,e2p5t,e2m0b0e3r;2A0p,ri2l0072,;20O0c3t;obJeurne152,,22000023; November 3, 2002; March Management: 2O0c0t3o;beMra2y0,9,2020020;3;NoJvuenren9b,e2r030,32002; March 5, 2003; April 7,29, Reportedby: "QMuaallitthyoAwsTs.urance AudBiSt.or 25 JDauten-2003 `Company Sanitized. Donotecontsain TSCACBI --~ Teeter H25130 FourWeek non Toxiy Stuy in se Ras --_ Drone CERTIFICATION We, the undersigned, from this study. declare that this Teport provides an accurate evaluationofdata obtained `EvalSuattrioincRetpoartteedbly:y Z<5 PropRescDhiCEliaEnn APVbuFv.cloofMgaissse " A8-Jh une-e2073 Assn Puclogy `Evaluation Reported by: SobDHiplao2)mansbAdYC3Fs,PE Principal ResearchPathologist . 25 duBnes-2003 AvsEaviRacnePsetonnaoaPgo:yr aon2 2S6ige ~~ PrincipeRe`SsteeavrencDhR.aoFmrhamsoe,AlD.VCd. VReisD.s Mag Date srtHAN Not 55 `Supervisor 28 SBauene-z0 Tasued by Study Director: EeTiSnet rVRieleetdhPhTl.eoArBoT 2Bobnea 2003 Company Sanitized. Dogs notcontain TSCA Cay - 1225511334: PFoouurrWWeeeekklInnbhoallautiioonnTTooxxiicciittyySSutdyyiinnMMaalleReaRtass_ ~ TABLE OF CONTENTS pDupoonmt1i1a4n14e Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT crc? QUALITY ASSURANCE STATEMENT voces} CERTIFICATION css LIST OF TABLES cosmos] LIST OF FIGURES ccc LIST OF APPENDICES corrosion STUDY INFORMATION ccs STUDY PERSONNEL ccrasmssssmssosommsmmssssssssssssmommmsncdd INTRODUCTION corrosion STUDY DESIGN sams 3 ~ MATArERTIESAGLUSIAACNHDESMEc THOr DS c ossc es s14 Bu C. TTESSUSSPEUOIBESS Eorv rssssresr enms menss es 14 1 21. 3. EACaNRgTVeAOaLBnCdHOICUaaSgIlNeGCRaOcDkOCNRL I.NG.E...o . os osrooe ss r 7114 1414 d 5. AF nimaale HeWaltd AhaTndEnviroMnORmHOernngPtT roagalm re 15 Fu ASSIG1U0GDIEONUDS..ocrrenrs emerson 16 321. BChAaPmObSeSrCMoOMnSS.Iion ad Desig... r1T7 17 H. C21.. hPTesataSrurbSszatatenDcceeiSoaltfmecpColeHinlnAr.gma.ebni.EdrAzATGOYaSSPtRiEToe.n.....v..s..s.ovowsoermne--ms--norne1ort11o77 I. B3.odEynvWiroenmeintaaglnMdohCnliittnoriicsnagl. ODSEIVALIwaOm--N--S ........ooovowerreretroensronresooowrsel1l8 JK.. FColiondicCal Poathonl0gsy aEunVIdUFmOAOOpdNEEFtGIEiNCYognio...r...rn orermormemrmeo veroneo orroro orron 1188 1. Hematanod Cloagoulagtiony.............. Company Sanilized.Doos netcontain ToA Cg) -- tsetse =H-2n 5134: TFoourw-WeeedkDIhnahalluaitioornTTooxxiicciittyySStuuddyyiinnMMaalleeRRatass_ DDuuppoontci11n4d1i4e TABLE OF CONTENTS (Continued) Page 4B2. UCRliBnEiBcGalOACVheEmiYse..c ....eroo smossno scsooreen msrmmmmHmUssmmmn--2--0 L. M. BIOOd FIUOFING RECOVEIY PETIO ABYSSc c.cvr reomsomn emssosesonson 20 21 ON.. ASnUatBoSmEiAcAPNaBtIhYoSlEOSgY EVAIUGHON memos nsession 21 23 RESULTS ANDDISCUSSION corms24 In-LAi.feCAhRaImmbaelrMCEROSUNFEMCENES c DOf tFheTAeso ttSUiBSIoANr CnE s nre owr er s2244 B.. C. BCohdaymbWeerigEhNtVsOaNnIdENBLoadly WCeOigMhtHGOAINNSS...........rc.orrrcoosvsecuseomrreeeereesoen2254 D. E. PFoosotd-CExpoosurne ClsiniacunadlFOmobsoepdrEvFaFttIiCoIniEsNaCoYnd Cnlinicva..l Observations at the TimeofBody25 Weight DEAEMIAONS ovo 25. ~ ClinAi.calHPaOthomloagyalEiVdAoCIOUlBAGtUOOINBNgvIOeNy.o ccs 26 26. B.. Co UCHlBIBCIaSlSICSRc ETMISITY co osm r osms2621 D. Pasaa0 UFNE FIMOTGE...vvrvsssrsososoos 2] B100A.d BFIIOUOOAFNFEIUAORBHINYESAIBSBIo YSIS cv rei mes221] ADatomic Pathology EVAIUAON cuvvvosssssssssssssssssms2n8 B. C.. OBA GOSS OWBESIEGIHVNSIc ONS c oo rr rs ee s. 28 29 1D. Ee MICIOSCOPiC COMCRISIONS r FIMHIo GS.com rrnne nnreero 2030 CONCLUSIONScorrosion31 RECORDS AND SAMPLE STORAGE... fsssnsmssmssssmmonsanns31 FIGURES sss8 --_ APPENDICESccna39 Company Saniized. Doesnotcontin TSCA CBI 0 H-25134: Four-Week Inhalation Toxicity Study in Male Rats --~ DuPont-11414) LIST OF TABLES Page I: CHAMBER CONCENTRATIONS OF H-28134 c.vvensnsseenmsossnens 38 2. PARTICLE SIZE DISTRIBUTION OF H-25134 ccs 38 3. CHAMBER ENVIRONMENTAL CONDITIONS ccc cmgpmmm---- 4. MEAN BODY WEIGHTS OF MALE RATS... i 5. MEAN BODY WEIGHT GAINS OF MALE RATS... 2 6. MEAN DAILY FOODCONSUMPTION BYMALERATS.d.... ssmmmmmmm-- 7. MEAN DAILY FOOD EFFICIENCY OF MALE RATS... signal 8. SUMMARY OF CLINICAL OBSERVATIONS IN MALE RATS PRIOR TO EXPOSURE........... 46. 9. SUMMARY OF CLINICAL OBSERVATIONS IN MALE RATS AFTER EXPOSURE... 7 10. SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS... 88 11. SUMMARY OF COAGULATION VALUES FOR MALE RATS cvs 50. 12. SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS .. consmmsmm-- 1 13. SUMMARY OF URINALYSIS VALUES FOR MALE RATS ............. sm 14. SUMMARY OF BLOOD FLUORINE ANALYSS....... -- iovmsmmsmndnmaS ~~ 15. MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 25 SACRIFICE............... 56. 16. MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 56 SACRIFICE...............59 17. INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE... oon 62. 18. INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY $6 SACRIFICE........ --1 19. DIANY 2C5 SIACDRIAEFNINDCELCESEIOc SN GRADES OF MICROSs COPIC OBSERVATIONSs IN MALE RATS 20. IDNACYID56ENSCAECSRIAFNIDCELESc ION Go RADm ES OFmMICs ROSCOPIC OBSERVATIONA S IN MALE RA. TS --~ Company Sanilized. Does not contain TSCA CBI eeeeet H-25134: rFoeur-eWekek InhaallatviionnTTooxriiccliyySStuuddyyiinnMMaalleeRRaattss __ --~ LOIFFS IGUT RES 1. SCHEOFEMXPOASUTRE IC SYSTEM.. 2 MEANDAILY CHAMBERCONCENTRATIONS... 3. MEAN BODYWEIOGFMAHLETRATSS... 4 MEANBLOODFLUOORFMAILENE RATS... DDuuoPmoenlt1i1a4n1s4. Page 5 86 81 88 LIST OF APPENDICES A. DAILY CHAMBERCONCENTRATIONS... Page 0. B. DAILY CHAMBER ENVIRONMENTALCONDITIONS... C- INDIVBOIDYDWEUIGAHTLS sms 93 98 ~~ D.. FE INDIFOVODICONDSUUMPTAIOLN. ..rsnsnsmmmsmneonn INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS... 103 109 F.. INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA ccc G. INDIANIVMALIBLDOODUFLUAORILNE .......eccesesen 126 150 H.. INDIVIDUALANIMALFINAL BODYANDORGANWEIGHTS 1 INDIANIVMALIPATDHOULOGAY L DATA.. cco 157 166 `Company Sanitized. Does not contain TSCA Cal ~~ - 1T 200Footo in isas pews STUDY INFORMATION Substance Tose: (NN Snonmscose: + H-25134 Submitter's Notebook Number(s: (NNER Haskell Number: 25134 CAS Registry NumberSENN Composition: | Physical Characteristics: Dark brown solid ~~ Stability: The test substance appeared to be stable under the conditions of the study; no evidenceofinstability was observed. Sponsor: E.L du Pont de Nemours and Company `Wilmington, Delaware 19898 USA. Study Initiated/Completed: October 4, 2002 / (sce report cover page) ~ Company Sanitzod. Does not contain TscA cay S NL m H:25134: Four Week Inhalation Toxicity Study in Male Rais -- DuPont 11414 STUDY PERSONNEL Study Director: Linda A. Malley, Ph.D., D.AB.T. Management: Arthur J. ONeill, 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. Anatomic Pathologist: John F. Hansen, D.V.M,, Ph.D. Management: Peer Review Anatomic Pathologist: Steven R. Frame, D.V.M., Ph.D. Steven R. Frame, D.V.M., Ph.D. Blood Fluorine Data Analysis: Vladimir Capka, Ph.D. Management: S. Mark Kennedy, Ph.D. Toxicology Report Preparation: Maryanne M. Wilford, B.A. Management: Nancy S. Selzer, MS. Laboratory Veterinarian: Thomas W. Mayer, DVM. ACLAM. -- CorPANY Sanitized. Doss notcontain sca cay a 125134: Four-Wesek InhalationToxicity StiunMdalye Rats Dupont-11414 --_ SUMMARY "The purposeofthis study was to assess the potential subchronic toxicityofexposure to H-25134 wineardeueltxpmoasleedrtatos.atYmoosupnhgeraeduclotntmaailneinCgrl0,:C5,D*30(,IGorS)1B0R0 rmagts/m(1?5Hr-a2t5s/1e3x4pofsour6re concentration) hours per day, over a d-week period for a total of 20 exposures. Body weight and food consumption were: determined weeklyand clinical signsof toxicity were monitored throughout the study. Blood samples were collected on test days 0, 7, 14, 25, and 54 for analysis of fluorine concentration. Blood samples and urine samples were collected at the endofthe exposure period from 10 rats/concentration for evaluationofclinical pathology and urinalysis parameters. After the last exposure, 10 rats/concentration underwent gross necropsy. Selected tissues were processed for histopathology and examined. Additional blood samples were collected for future analysis of perfluorooctanoic acid (PFOA) concentration. At the endofan approximately one-month recovery period, blood samples and urine samples were collected from all surviving rats for evaluationofselected clinical pathology and urinalysis parameters, and fluorine concentration. All surviving rats underwent gross necropsy, selected tissues were processed for histopathology, and were examined by light microscopy. Test substance-related, statistically significant decreases in body weight gain and food efficiency occurred in rats exposed to 30 or 100 mg/m'. Although slightly decreased body weight gain for rats exposed to 5 mg/m? also appeared to be test substance-related,itwas not considered to be ~ ``maodrvtearlsietysidnicdentohte omcecaunr dbuordiyngwetihgehsttsudwye.reInocnildyen4c.e3so%flocwlienrictahlansitghnescfoonltlroowlivnaglueex.poUsnusrcehaenddulated the timeofbody weight determination were similar for all groups. Cholesterol concentration was mildly decreased in males exposed to 100 mg/m" at test day 25; these changes were considered to be potentially adverse. After 31 daysofrecovery, cholesterol concentrations for all test groups were similar to control. Triglycerides were mildly decreased in malesexposedto 5, 30, or 100 mg/m'. Although these changes showed a flat concentrationresponse, they were considered to be test substance-related. However, the mildly decreased concentrations were not associated with histological changes, and therefore, they were not considered to be adverse. After 31 daysofrecovery, the triglyceride concentrations for all test `groups were similar o the control values. Blood fluorine (but not plasma fluoride) concentration was slightly increased above background concentration in rats exposed to 30 or 100 mg/m'. Urine fluoride was also increased in rats exposed to 30 or 100 mg/m". At the endofthe one`month recovery period, blood fluorine concentrations and urine fluoride amounts were similar to control. There were no other treatment-related changes in clinical pathology parameters for any test group. Statistically significant changes in organ weight and relative organ weight (relative to body weight or brain weight) that were secondary to decreased body weight occurred in the heart and testes. Squamous metaplasia/hyperplasia ofthe ventral laryngealmucosawas observed in rats exposed to 5, 30, or 100 mg/m' at the sacrifice on test day 25. The lesion was minimal, focal, ,~ andnot concentration-related with respect to incidence or severity. Squamous metaplasia ofthe TTT Company Seed. Dosa not contain TSCA Cor H25134: Four Weck Inhalation Toichy Sudy in ae Rats Dupont 11414 ~~ ventral larynxofrats is a common, nonspecific response to irritants and is generally considered raencoavdearpyt.ive response. This lesion was not present in animals sacrificed aftear one-month `The no-observed-effect level (NOEL) for this study is defined as the highest concentration at `which toxicologically important effects attributable to the test substance were not detected. Thus for this study, the NOEL is equivalent to the NOEL as defined by the United States Environmental Protection Agency (1985), and the no-observed-adverse effect level (NOAEL) as. defined by the European Union (1994). Under the conditionsofthe study, the NOEL was 5 mg/m based on decreased body weight gain at 30 mg/m? and above. The minimal `morphological changes in the larynx observed at all exposure concentrations were considered to `be a nonspecific, adaptive response and isofequivocal toxicological significance. -- -_-- Company Sanitizgq, Dossnote notontain Toc ogy 1.25134: Fou Week Inhalation Toxicity Study in Male Rats DuPont 11414 --~ INTRODUCTION `The test substance contains an organofluoride melt additive and is used as a protectant for textiles. The exposure concentrationsofthe test substance were selected on the basisof rangefinding exposures and a knowledge about the physical and chemical propertiesofthe test substance. Inaone-week range-finding study, groupsof male rats were exposed t0.0, 5, 30, or 100 mg/m H-25134 for 6 hoursperday for 5 consecutive days. There were no test substance-related effects on clinical signs or body weight for any exposure concentration. The 4-hour approximate lethal `ccoonncceennttrraattiioonns(fAoLrCt)hewmaasidnestteurdmyinweedretosbelee3ct7e7d mtogb/em0.,)5, B3a0s,eadndon1t0h0esmeg/dmat'a., the exposure `The objectiveofthis study was to evaluate the subchronic toxicity of H-25134 when `eaxdpmoisneisdtgerreodupboyfimnhaalleatriaotns tsoermvaeldeaCsrtlh:eCnDeg(aStDiv)eIGcoSntBroRl.ratTshoevienrhaal4a-tiwoenerkopuetreoiofd.exApnosauirre- was chosen because it is the potential route for human exposure. STUDY DESIGN ~ F5,o3u0r,gorrou1p0s0ofmgm/aml'.e rTathse(1fi5rsrtat1s0eraacths)pwerergeroeuxppowseerde tdoesciogncneantterdatfoironssuobfcHh-ro2n5i1c 3to4xitcairtgy,etaenddtoth0e, remaining rats per group were designated for blood fluorine analysis and recovery. Rals were exposed nose-only for 6 hours per day foar total of 20 exposures (excluding weekends), Throughout the exposure period,bloodwas collected weekly from the rats designated for blood fluorine analysis. At the endofthe exposure period, blood and urine samples were collected for clinical analyses, and 10 rats per group were sacrificed for pathology examination. Al remaining rats were allowed to recover for approximately a 4-week period. At the endofthe recovery period, all surviving rats were bled for blood fluorine analysis and sacrificed for pathology examination. All rats were weighed weekly during the exposure phaseofthe study. At every weighing, cach rat was individually handled and examined for abnormal behavior and appearance. During the daily exposures, rats were checked for viability. Immediately following each exposure, each rat was individually handled and examined for abnormal behavior and appearance. The amount of food consumed by each rat was determined weeklyduring the exposure phaseofthe study. Surviving rats were weighed and individually observed for clinical signsoftoxicity throughout the recovery period. -- - #0 contain re,Cacp H-25134: FourWeek Inhalation Toxicty Study inMaleRats ~ MATERIALS AND METHODS Dupont11414 A. Test Guidelines "The study design complies with the following test guidelines: + Organisation for Economic Co-Operatiaonnd Development (OECD) (1981). 412 Repeated Dose Inhalation Toxicity: 28-Day or 14-Day Study. Guidelinefor Testingof Chemicals. B. TestSubstance `The test substance, H-25134, was supplied by the sponsor as a dark brown solid. Purity was not supplied by the sponsor. The test substance was assumed to be stable throughout the exposure: phaseofthe study; no evidenceof instability was observed. C. Test Species RAalteoitaglho,fNo6r6tmhaClaeroClrilna:.CDTh(eSmDa)IlGeSraBtsRwreartsewaapsprroexciemiavteedlfyr5omweCehakrsloelsdRoinvetrheLadbaoyroaftoarrriievsa,l.Inc., Rats have historically been used in safety evaluation studies for inhalation toxicity testing. The ~ eCxrtle:nCsDiv*e(SeDxp)eIrGiSenBceRwriatthwtahse ssetlreacitneadtbHaassekdelolnLcaobnosriasttoernyt.ly acceptable health status and on D. Animal Husbandry 1. Animal Housing Rats were housed singly in stainless steel, wire-mesh cages suspended above cage boards. 2. Cage and Cage Rack Changes Cages and cage racks were changed at least every other weck. 3. Environmental Conditions Rats were housed in one room in proximity to the inhalation chambers. Animal rooms were targeted at a temperatureof23 2 1C and a relative humidity of 50 = 10%. Animal rooms were artificially illuminated (fluorescent light) on an approximate 12-hour lightdark cycle. Excursions outsideofthese ranges on 2 occasions wereof insufficient magnitude and/or duration to have adversely affected the validityofthe study. ~~ - CompanySant,2d. Do not contain TS gy 12H5:21531344:; FFoouurrWWeeeekk IInnhhaallaattiioonn TTooxxiiceittyy SStuuddyyininMMaalleeRRaattss ~ 4. Feedand Water Dupbonwti11d4t1d4. Eaxncdetpatp dwuartienrgweexrpeosauvraeisl,abPleMaId Nliubtirtiutmi.onDIunrtiernngattihoenaulr,inLeLcColCleercttiifoinepderRioodde,nrtatLsawbeDrieetfas5t0ed02 overnight for approximately 16 hours; water, however, was available ad libitun. 5. Animal Health and Environmental Monitoring Program AfosllsopewciinfgiepdroicnetdhuereHsasakreelpleLrafboorrmaetdorpyerainoidmicaalllhyeatlothenasnudreenthvaitrocnomnetnatmailnamnotniltevoerlisnagrepbroeglroawm, the those that would be expected to impact the scientific integrityofthe stud: + Water samples are analyzed `and other contaminants. for total bacterial counts, and the presenceofcoliforms, lead, + Feed samples are analyzed for total bacterial, spore, and fungal counts. + Sbyamtphleecsagferwoamshferress.hly washed cages and cage racks are analyzed to ensure adequate sanitation rCeerqtuiifrieemdeanntismaanldfneoetd tios uesxecde,egdusatraatnetdemeadxbiymtuhemmcaonnucfeancttruarteirontsoofmkeeetyscpoencitfaimeidnannuttrsi,tiionncalluding ~ psrpeecsiefniceedohfeathveysemectoanlts,amaifnlaatnotxsinb,eclholwortihneamteadxhiymdruomcacrobnocnesn,traantdioonrgsatnatoepdhobsyphtahteemsa.nuTfahceturer `would not be expected to impact the integrityofthe study. `lTahbeoraantiomraylanhieamlatlhvaentedriennavriirano.nmeEnvtaalluamtoinoinotofrtihnegsperdoagtraadmiidsnaodtmiinnidisctaetreedanbyyctohnediattitoennsditnhgat affected the validityofthe study. E. Pretest Period Upon arrival at Haskell Laboratory, all rats were housed 1per cage in quarantine. The rals were: + quarantined for 6 days. + identified temporarily by cage identification. + weighed 3 times during quarantine and once prior to initiationof exposures. + observed with respect to weight gain and any gross signsofdisease or injury. `bTahseisroaftsbwoedryewreeilgeahstesdafnrdocmliqnuiacraalnstiignnes.by the laboratory animal veterinarian or designee on the 2 - Company Sanitizeg,Does *Doesnotcongin TSCA og, 125134: Four-Week Inhalation Toxicity Study in Male Rats Dupont 11414 ~~ F Assignmentto Groups aRnatysclwienricealsesliegcntseodffodriusesaesoenorstiundjuyryo.n Tthheeybawseesroefdiasdterqiubautteedbboydcyowmepiugthetrigzaeidn,asntdratfirfeieeddom from randomization into study groups as designated in the Study Design, so that there were no sstealteicstteicdalrlaytssdigindifnioctanetxcdiefefder+en2c0es%oafmotnhegmgeraounpwbeiogdhyt.weTighhetfmiresatn1s0.raTthseinwceaicghhtgrvaoruipatwieorneof designated for subchronic toxicity, and the remaining rats in each group were designated for blood fluorine analysis and recovery. A6f-dtiegritasHsaisgknemlelnatnitomaglronuupsm,beeracahnrdatanwaisndhioviudsueadl icnadgieviiddueanltliyf.icaEtaicohn nrautmbwears.asAsfitgenreadsasiugnnimqeunet to groups, the cage identification number was tattooed on the tailofeachrat. The Haskell animal number and cage identification number were both included on the cage label. Atstudy start test day 0), male rats were approximately 7 weeksofage and weighed between 245 and 306 grams. On test day 0, when possible, ras with body weights that are not within + 20%ofthe mean were removed from study and replaced with rats having body weights within that range (subject to the same selection criteraisa the original rat). Rats that were not assigned t0.a test group or which were removed from study on test day 0, for out-of-ange body weights, were released for other laboratory purposes or sacrificed by carbon dioxide asphyxiation and discarded without pathology evaluation, at the discretionof the study rn director. G. Inhalation Exposure System (Figure 1) 1. Atmosphere Generation `Chamber atmospheres were generated by heating the test substance in a glass 250, 500, or 1000 mL, three-necked flask. The test substance was stirred constantly during heating using stir rods attached to FMI pumps. The flasks were heated to 280C usingeither a 500 or 1000 mL. heating mantel. A measured amountofthe test substance was added to the flask prior to heating. Houseline-air was metered into the flask with a Brooks Flowmeter. The resulting particulate stream exiting the flask was split between the inhalation chamber and a collection flask that removed excess test material from the air stream. The particulate stream was further mixed with dilution air, controlled by a Brooks Mass Flow Controller, at the topofthe inhalation chamber. A stainless steel baffle was used to ensure a homogeneous distributionofthe particulate stream through the chamber. Tubing between the generation flask and the chamber was heated by heat tape controlled with a Variac voltage controller. Vacuum pumps controlled the exhaust and the amountofai that was split from the generation stream to the collection flask. The heating. mantel and mass flow controllers were controlled and monitored by the Camile Inhalation Toxicology Automated Data System (CITADS). Since the test material was a solid, waxy ~~ material prior to heating, the heating mantels and stirring rods were tured on prior to placing the ComPony Sanitzed. Doss otcontain Ts -- a 12:325113344:FFoouurr-WWeeeekkInIhnahlaalttiioonnTTooxviiciittyySSutuddyyiinMMalleeReatsss DuDPuoponncti1i1d4i1d4 #TM traersgtertaitneemrpsecroanttuarien,itnhgetrhaetrsawtserien tphleaccehdaimnbtehreppoorrtthohloelse.s, aWnhdetnhethdeaihleyaetixnpgosmuarnetewlarseiancihtieadtetd.he `hTehaetianngimmaalnstewlesraenedxsptoisrreedrsfowrer6ehtouurrnsaedftofrf,beainndgthpelarcaetsd wientroetrheempoovrtehdolfesr.omAtfhteecrh6amhboeurrss,. the 2. Chamber Construction and Design Ainltleernxaplovsuorleumcehaomfb1e5r0s Lw.erAe cboafnfslteruicntseiddoeftshteacihnlaemsbsesrteperloamnodtegldaussni(fNorYmUcshtaylmeb)ewritdihstarniobumtiinoanlof the test atmosphere. 3. Exposure Mode Dcounriicnagl enxopsoesupireec,esa.niTmahlesrwesetrreaiinnedrisvwideuraelliynsreerstterdaiinnetdo i2nppoelryfmoertahtyedlmsettahianlcersyslsatteeelacnydlistnadienrlseswsith setxeteelnfdaecdepilnattoetwhheiecxhpowsausreatcthaacmhbeedrt.o tAhpeperxopxoismuarteelcyha|mwbeeerksobetfhoartethtehensotsaerot fofetahceheaxnpiomsaulre phase, dayto animals were acclimate the placed in restrainers on 2 animals to the restrainers. separate days for approximately 15 minutes each H. Characterization of Chamber Atmosphere -- I. Test Substance Sampling and Analysis "aTphperocxonicmeantterlayti6o0n-moifnHu-t2e5i1n3te4rvianlseadcuhricnhgaemabcehrewxapsosduertee,remxicneepdtbfyorgrtahveicmoenttrrioclacnhaalmysbiesr,atwhich wtharsoungoht saa2m5plmedm. fKinleowcanssveotlteumtehastocfoncthaaimnbeedraaptem-owsepihgerheedweGreelmdaranwgnlafsrsofmibtehre(sTaymppeliAnVgE)port afiulteorm.atTihcealfliyltterrasnwseferrerewdetoitghehoCenIdTaACDaSh,nwmhoidcehlcaCl-c3u3laMtiecdrtohbealcahnacmebe.r Tcohnecefnitlreartwieoingshbtassweedroen atthemodsipffheerreencseamipnlperde.- aGnrdavpiomsett-rsiacmpslaimnpglfeilsttearrwt-eiagnhdtsstdoipv-itdiemdesbyfotrhceavcohlsuammepolfewcehraemablesro controlled and recorded by CITADS. 2. Particle Size Determination Aparstaicmlpelseletsosdtehtaenrm1i,n3e, paanrdti1cl0eusimzedidiasmtertiebru)tiwoans(mtaaskesnmferdoimaneaacehrotedsytncahmaimcbdeirasmeotnecreapnedr wpeereckent witha Sierra Series 210 Cyclone Constant Flow Air Sampler. Prescparator/Cascade Impactor and Sierra Series 110 3. Environmental Monitoring `hCohuarmabnedrwaairsflmoowniwtaosrseedtacotnttihenubaelgliynwniitnhgoafcealaicbhraetxedpoBsruoroektsomaocdheilev5e8a5t1lEeasMta1s2saFilrocwhanges per ~ Controller. Chamber temperature was targeted at 22 3C and was measured with an Omega "17+ Company Saniizeq, ose netoxvtars Tacs ogy 125134: Four Week Inhalation Toxicity Studyin Male Rats DuPont 11414 ~~ tJhuemromomcoodueplleP.TC10h0amwbeet-rbruellba/tdirvey-hbuumlibdrietsyiswtaasncteatregemtpeedraattu5r0e+de2te0ct%orasn.dAwiarsflmoewa,stuermepderwaittuhre, ainntderrveallastidvuerhiungmiedaicthyewxeproesumreo.nitCohraemdbceonrtoinxuyaglelny wcointcheCntIrTatAiDoSn waansd traercgoertdeeddtaotb1e5a-tmilenaustte19%. Chamber oxygen and was recorded concentration was twice during each measured exposure. with a Biosystems model 3100R Oxygen Analyzer I Body Weights and Clinical Observations Aelxlamraitnsewdefroerwaebingohremdalonbceehaaviwoereka.ndAatppeevaerraynwceei.ghing, each rat was individually handled and Awfetreerclhoeacdkiengd tfhoer avinaibmiallitsyipnrtioorthteorceastcrhaienxepross,uarned,2pltaoci3ngtitmheesrdeustrrianignetrhseienxtpootshuerec,haamnbderats,threats endofthe exposure, prior to removing them from the chamber portholes. Each rat was individually handled and examined for abnormal behavior and appearance when it `was removed from the chamber at the endof the daily exposure period. Fur stains and hair loss associated with restraint and depositionofthe test substance were not recorded for individual rats following the daily exposures. Cage-site examinations to detect moribund or dead rats and abnormal behavior and appearance --~ `among rats were conducted prior to loading the animals into the chamber on exposure days, and atleast once daily on non-exposure days. J. Food Consumption and Food Efficiency `The amountof food consumedbyeachanimal over each weighing interval was determined by weighing each feeder at the beginning and endofthe interval and sublracting the final weight and the amount of spillage from the feeder during the interval from the initial weight. From these `measurements, mean daily food consumption over the interval was determined. From the food consumption and body weight data, the mean daily food efficiency were calculated. Food consumption and food efficiency were not determined during the recovery phase. K. Clinical Pathology Evaluation A clinical pathology evaluation was conducted onthe first 10 rats/group approximately 25 days after initiationofthe study. The day before collectionofsamples for the clinical pathology evaluation, the animals were placed in metabolism cages. These animals were fasted overnight (approximately 16 hours) and urine was collected from each animal. Blood samples for hematology and clinical chemistry measurements were collected from the orbital sinusofeach animal while the animal was under light carbon dioxide anesthesia. Blood samples for -- cwohaiglueltahteioannipmaarlamweatserusnwdeerrecacorlbloenctdeidoxatidseacarniefsitcheefsirao.m tAhdediatbidoonmalinballoovdencaolclaecvtaoedfferaocmhtahneimal -_ Tie ComoanySeniized. DosnotcominTSCAE 22H5e12531434:: FFoouurr-WWeeeekk IInnhhaallaatiioonnTTooxxiicciittyySutuddyyiinnMMaalleeRRaattss DuDbuopnocnltla11i41d4. = pvleansamcaavflauowraisded.ivTihdeedsienctoond2 aalliiqquuootts.waOsnperoacleisqusoetdwtoasplparsomcaesasnedd ftoropzleansamta-f2o0raCnafloyrsfiustourfe aatna-l8y0sisCofforPpFoOsAsi)b.leAfdudtiutrieonanaallybslioso.dBwoansepmlaacrerdoiwnsamseearrsumweturbee,prperpoacreesdseadt tthoessearcurmi,fiacendfrsotomraeldl nsuercveisvsianrgyatnoismuaplpso.rtBeoxnpeermiamrerntoawlsfmiendairnsgsw.ere stained with Wright's sain, but analysis was not 1. Hematoloagndy Coagulation Blood samples were evaluated for quality by visual examination prior to analysis. Complete abnlaoloydzecrouonrtsd,etienrcmluidniendgfrreotimcumlioccryotsesc,opwiecreevdaeltueartmioinnoefdtohneabBloaoydersmeAadrv.iaWr1i2g0hth-esmtaationeldogbylood asmnedaervsalfuraotmioanlolfacneilmlaullsarwemroerpehxoalmoignye.d Bmliocroodscsompeiacrasl,lsytafoirnecdonwfiitrhmanteiwonmoefthayulteonmeatbleude,rewseulrtes prepared from cach animal undergoing a hematology evaluation but were not needed for examination. Coagulation times were determined on a Sysmex CA-1000 Coagulation Analyzer. `The following hematology and coagulation parameters were determined: red blood cell count red cell distribution width hemoglobin absolute reticulocyte count hematocrit platelet count `mean corpuscular volume white blood cell count ~ `mean `mean corpuscular corpuscular hemoglobin hemoglobin concentration mdiifcfreoresnctoipailcwbhiltoeodblsomoedarceellxacmoiunnattion prothrombin time activated partial thromboplastin time: 2. Clinical Chemistry 7S1e7ruclmincilcianliccahlecmhiesmtirsytarnyaplayzrearm.etPerlsaswmearefldueortiedremiwnaesddoentearRmoicnehde uDsiaignnagospthiicls2(pBMHC)m/etHeirtaacnhdia fluoride-selective electrode. "The following clinical chemistry parameters were determined: aspartate aminotransferase: alanine aminotransferase sorbitol dehydrogenase: alkaline phosphatase: total bilirubin urea nitrogen creatinine cholesterol -- total protein albumin globulin calcium inorganic phosphorus. sodium potassium chloride --_ god. DOSS OH -_-- H2-925113344:: PFoouurrWWeeeekkIInnhhaallaattiioonn TTooxxiicciittyySSuuddyyiinnMMaalleeRRaattss _ ~ triglycerides glucose fluoride DuDbuPoonnv1i1l4d1i4a 3. Urinalysis Urine volume and appearance (quality, color, and clarity) were measured and evaluated visually, Areustpoecmtaitveeldy.UrUirnienCehceomnissttitruyenatnsalwyezerre. seUmrii-nqeuapnrtoitteaitniwvealsy mmeeaassuurreedd oonn aa RBoacyhere CDliiangintoeskticAstlasTM (ABdMvCaYnHceidtaOcshmiom7e1t7ercl3i9n0i0ca.l cUhreimniestfrlyuoarniadleyzwears. dUertienremionsemdoluasliintgyawpashid2letperHmmienteedruasnidngaan fluoride-selective electrode. Sediments from all urine specimens were evaluated `microscopically. "The following urinalysis parameters were determined: quality color clarity volume opsHmolality glucose ketone bilirubin blood urobilinogen pfrloutoeriidne" microscopic urine sediment examination ~~ 4 Recovery Near the endofthe recovery period blood and urine samples were collected from all surviving, rats accorditnog the procedures described above. The following parameters were evaluated according to the methods detailed above: cholesterol, triglycerides, total protein, albumin, globulin, and urine fluoride. L. Blood Fluorine Analysis On test days 0, 7, 14, 21, 25, and 54, blood (approximately 0.5 mL) was collected from the orbital sinusofdesignated animals (5 rats/concentration), while the animals were under light carbon dioxide anesthesia, for total blood fluorine analysis. On the dayofblood collection, blood was collected from the animals approximately 1 hour after the daily exposure. The blood was collected in plastic tubes containing EDTA while on ice and stored frozen. "The total fluorine content ofthe blood samples ws determined on selected blood samples using a Wickbold torch combustion method, followed by analysis with a fluoride ion selective: electrode. The liquid blood was decomposed or volatilized in the presenceofwet oxygen and swept through an oxy-hydrogen flame in a closed quartz apparatus. The combustion products were collected in an aqueous absorbing solution and analyzed using a fluoride ion selective ~~ ae Fluoride detere mination was analyzed on EDTA plasma. `Company Saniized. Docsesnrootcontain TSCA CBI Fluoride determination was analyzed from urine with EDTA added. -_-- H2He521513344::FFoouurrW-WeeeekkIInnhhaallaattiioonnTTooxxiiccihtyySSutuddyyiinn MMaalleoRRatass DDuuPPoomnetl.i11d4l1g4. ~ electrode. records. Rationale for the numberofblood samples analyzed was documented in study M. Recovery Period tbltohodefclounocrliunesiaonnaolyfstihsew4er-eweaelkloewxepdostuorreecpoervieordf,otrhaep5prroaxtsimpaetrecloync1emntornatthi.onDduersiinggnattheedrfeocrovery pweeriigohdi,negx,peoascuhrersatwwearse innodtivciodnudaulcltyehda;nhdolweedvaenrd, bexoadmyiwneeidghftosr awbenroercmoalllebcetheadvwieoerkalyn.dAtevery aappppeeaarraannccee.amCaogneg-sriattesewxearmeincaotnidouncstetdo doentceectdamiolyr.ibund or dead rats and abnormal behavior and As described in section L. endofthe recovery period above, blood (test day 54). samples for blood fluorine analysis were collected at the N. Anatomic Pathology Evaluation `saTcerniafinciemaalnismpaelrs)g.roTuhpewoetrheersaScrainfiimcaeldsapnedrngercoruoppswieerdefoalllloowwiendgttohreelcaosvteerx(proescuorveer(iyniatniialmals) for approximately 4 weeks and were then sacrificed and necropsied. rr Rats were cuthanatized by were performed on all ats. carbon dioxide anesthesia and exsanguination. Gross examinations --~ -_-- Company Sa!zed. D065 akconainTSCA cB He25134: Four-Week Inhalation Toxicity Study in Male Rats Dupont-11414 ~~ The following tissues were collected from rats that were found dead or sacrificed by design. Digestive System liver esophagus stomach duodenum jejunum ileum cecum colon rectum salivary glands pancreas Urinary System kuirdinnearyysbladder Cardiovascular System heart aorta Hematopoietic System spleen thymus `mandibular lymph node mesenteric lymph node bone marrow* Endocrine System pituitary gland thyroid gland padarreantahlyrgoliadngdlsands Musculoskeletal System skeletal muscle femur/knee joint sternum Reproductive System testes epididymides prostate seminal vesicles Mskiisncellancous eyes (including optic nerve) gross observations" Respiratory System lungs trachea -- nose (4 cross sections) larynx pharynx Nervous System braicne(rienbcellulduimn,gmceedruelblrau/mp,ons) spinal cord (cervical, `mid-thoracic, lumbar) sciatic nerve: ab BGroonsesmcabrsrerovwtwiaosnscomlaldecetaed wnietchrotphsefyefmoruwrhaincdh shiesrtuompa.thology is not eppropiste (c.g. uid, ruffed fr, and missing anatomic parts) will generally not be collected. `wTehreeliwveeir,ghkieddneatysn,eclruonpgssy,,heaanrdt,osrpglaenenw,ebirgahitnf,itnhaylmbuosd,yadwreeingahltgalnadndosr,gtaenstweesiagnhdt/ebpriadiindwyemiigdhets ratios were calculated. Final body weights determined just priotor necropsy were used in the assessmentoforgan weight changes T1e0st%esn,euetpriadlibduyfmfiedreesd,faonrdmaelyiens. wPerroecefsisxeedd itnisBsouuesinw'esrseoleumtbioend.deAldliontphaerraftfiisns,uecsutwearteafnioxmeidnianl thickness of S micrometers, stained with hematoxylin and eosin (H&E), and examined `microscopically. Aclolncceonltlreacttieodntgirssouuepssfwreormerpatrsocseacsrsiefdicaenddatretcheeievnedaodfftulhleheisxtpoopsautrheolpoegriicoadl ferxaommincoanttiroonl. anTdhehigh pharynx/larynx was identifiaesd a target tissuebyhistopathology, and was processed from the ~~ lgroowuapnrdeciontveerrmyeadniiamtaelsg.roup initial sacrifice animals and from the control and high exposure es notconaTM156 compen sanitizedO: -= H2S134: Four Week Inhalation Toicky Sudy in Mal Rats Dupon-1414 #= paTthheokleoygtyottahbelepsaatnhdolaopgpyenldeiscieosn.grading system used in this studycanbe found within the O. Statistical Analyses Significance was judged at p < 0.05. f Parameteo r ] Preliminary Test ExipDooaiselCioDncaetrraaton Blood Fluorine Anlyis BBooddyy WWeeiiygghhtt Gain O`FFroogooaddnECWofeniisegunhmtpctyion Treience of Cid] Testor lackofrend" ryenhge StapWiiek sr sEipgnriefiTcmaintary testis vot s[ipgrneifliicmainntary tv Descriipt.ive siaistic (8. mean, siandard deviati"on) | htSheeeJoenJocnrkchaeearpep-cTeartpsotnra ||pFarieruwmiisneacroymtpeasrtsisfoorn [|vOarrieavnceeyfmolilonwoedlwith ||lKowaedWwailthiDuennt's | Dunes es es ~ ~ Clinical Pathology [Soo mene[os revalyomweeadrit | o[KluiysDautis normal a sPiaginriwfiisceanct omparanidsssoocintesd preliminary esartonsly conductedif the tsforlaofcrek i. b7etushedS.hapfihroeWiSlhkapitreostWsinkottseistgniisfsiciagnntifboitcaL,evKernucs'ksale-sWtalilssiisgnsifticsanfto,llorwoeadsbtyveDrosmi'osofeDt.uets st wil. BIotnfherirnocniidecnocemcsinoonsiigsniefdi.cant,bt asignificant lack of it occurs, hen Fishers Exact est witha 4 WlhfenhaemreicnodridviedduvalalOeb.seFrovartieoxnamplre,ebcoirasldbeeiindsgplerssiheanadac<0.e1, r0i.v0alsu,uscedaforlaneyacuarlclpuleaaftoioirnmsoodson perormed with that bili dat. --~ _-- Gompeny sanitizedva posses1sCACE! H:25134: Four-Week Inhalation Toricity Study in Male Rats PS RESULTS AND DISCUSSION DuPon-11414 In-Life Animal Measurements A. Chamber Concentrations of the Test Substance (Tables 1-2, Figure 2, Appendix A) `The mean concentrations standard errorofthe mean for the gravimetric samples over the 21000exmpgo/smur,esrewseperceti5v.e1ly.0.D1a9i,ly3m1e+a0n.c9o3,ncaenndtr1a0t0ions2.r4anmgge/dmf?rionmc7h4a-m1be3r8s%otfargtehteendoamti5n,al30, and concentration for the 5 mg/m? group. Daily mean concentrations ranged from 67-123%ofthe nominal concentration for the 30 mg/m' group. Daily mean concenirations ranged from 66120%of the nominal concentration for the 100 mg/m' group. Although the mean daily chamber concentrations were occasionally less than 90%of the nominal concentrations, the mean concentrations for each week were consistent (Figure 2), and were acceptable for evaluating the toxicity at the targeted concentrations. `The mass median aerodynamic diameter (MMAD) ranged from 3.0-3.8 pm for the 5 mg/m -- ``ggreooumpe,tr4i.c7-s5t.a2ndyamrdfdoervtihaeti3o0n m(gG/SmD') group, and 3.94.5 pm ranged from 1.5 to 1.6 for for the the 100 mg/m' group. The 5 mg/m' group, 1.7-2.0 for the 30 mg/m? group, and 1.4-3.1 for the 100 mg/m group. In the 5 mg/m' group, 0.2-0.4%ofthe particles were less than | pm, 32-50%ofthe particles were less than 3 pum, and 98-100%ofthe particles were less than 10 um. In the 30 mg/m? group, 0.1-0.2% of the particles were less than 1 um, 20-32%of the particles were less than 3 pm, and 93-100%ofthe particles were less than 10 um. In the 100 mg/m' group, <1-7% of the particles were less than | pm, 10-70%ofthe pianrdtiiccalteestwheatrethleesgsentehraanti3oinms,ysatnedm9p9r-ov1i0d0e%dopfatrthieclpeasrttihcalteswewreereinlteshse trheaspnir1a0blpemr.anTgheefsoerdraattsa. Nominal concentrationsofthe test substance were not calculated since a portionofthe air stream containing the test substance was diverted to awater scrubber. B. Chamber Environmental Conditions (Table 3, Appendix B) `The overall mean chamber temperatures in the 4 exposure chambers during the 20 exposures were 21-25C. The temperature rangeofthe daily means for all 4 chambers was 19-25C. Although the chamber temperatures slightly exceeded the targeted range of22-24C, the slightly Tower and higher temperatures did not adversely affect the healthof the animals, based on their clinical appearance. --_ -_--mNm Company Sanitized. Does not contain TSCA Cal --- mmm Fr SHZ-251:34: TFoouurr-WWeeeekkIInnhhaallaattiioonnTToorxicciityySSutuddyyiinnMMaalleeRRaattss ___ DuDuppoonnte1l1d41i4s --~ T65h%e.oveTrhaellhmumeiadnitryelraatnivgeeohfudmiadiiltyymienatnhse 4forexapllos4ucrheacmhbaemrbsewrsasdu3r3i-n7g4t%h.e 2T0heexsploisghutrleyshwigahser37- hapupmeiadriatnycev,alues did not adversely affect the healthofthe animals, based on their clinical `5T0heL/omvierna.llTmheeaanircfhlaowmbienrthaeircfhlaomwbienrthwea4s eadxepqousautree ctohaamchbieervsedautrlienagstth1e22a0irecxhpaonsguersespewrahsou3r5.- C. Body Weights and Body Weight Gains (Tables 4-5, Figure 3, Appendix ) Ahowneonv-elri,netahre dmeecarneavsaeliunesbowdeyreweoinglhytstgaatiinstwicaaslloybssigenrivfeidcamnatlfeosretxhpeo3s0edatndo 15,0030mgor/m1'00 mg/m, cvoanlcueenstwraetrieonslsigfhotrltyes(tnodtaystsat7i-s2t1icaalnldy)olvoewrerthtehianntetrhvealcoofnttreosltvdaalyuses0-b2y5.tesMtedaany 2b5o.dyThweeilgohwter bcoondsyuwmepitgihotngaanidn wsiagsnicfoircranetllayteldowwietrhfsoloidghetflfyiclioewnecry(vnaoltuestsatfiosrtimcaallleysseigxnpiofsiecadntt)o f3o0odor 1co0n0trmogl/sm.'.AltIhnoaudgdhitaiocnl,eadrurcoinncgetnhterarteicoonv-erreysppoernisoed,retlhaetiboondshyipweiisgnhottgeaviidnevnat,luweshewnertehesilmoiwlearr to `cboondsyumwpetiigohnt,gafionodfoerfftihceiernatcsy,eaxnpdostehde troec3o0v,earnyodf1t0h0emseg/pmar?aimsectoenrssidduerriendgttohgeetrheecrowveirtyh ptehreifodo,od ~-- tahdevedrescerefaorseadtsboedxypowseeidghttog3a0inorap1p0e0armsg/tom'b.e test substance-related and is considered to be D. (FToaobdleCso6n-s7,umApppteinodniaxnDd)Food Efficiency 1F0o0odmgc/omns?ucmopmtpioanrewdastostlhieghctolnyi(rnooltvsatlautei.stiIcnalaldydsiitginoinf,icfaonotd) lefofwiecrieinncmyawlaess seixgpnoifsiecdanttoly30loowrer 2f1o.r rTathseesxepoobsseedrvtaot3io0nosrco1r0r0elmagte/mw'itdhutrhienglotwesetrdbaoydsy14w-e2i1g,htanadndovweerigthhet ignatienrvvaalloufetsesotbsdearyvsed0-in tsthaetsiestgircaolulpyss,iagnnidfiwcearnte cchoanngsesidinetfrooboededctoensst usmupbsttiaonnceo-rrefloaotdedefafnidciaednvceyrsoeb.serTvheedreinwmearleenso exposed to 5 mg/m'. E. PostExposure Clinical Weight Determinations Observations and Clinical Observations at the Time of Body (Tables 8-9, Appendix E) Post-exposure Observations `eTxhpeorseuwreergeronuopadfvoelrlsoewionfgttehset sdauiblsytaenxcpeo-sreulraetpeedrciloidnsi.calThsiegnisnocifdteonxciecsoitfy odbisscehravregdeifnraonmythe -- eyelnose were similar among all exposure groups and are commonly observed in rats restrained 25 Company Saniasd. Doss notconiam TSCA CHI a HHo:2255113344::FFoouurr-WWeeeekkIInnhhaallaattiioonnTTooxxicitySutuddyyinnMaalleeRaaiss__ DuDpuoPonnetli11a4i144 ~~ ifunrn/osskei-nosntlayinisnahsasloactiiaotneedxwpiotshuruerisnyasttieomnsa.ndCldienfieccaaltsiiognndsourfinhgaierxlpoosssudrueewteortehenortesrtercaoinredresd, faonrd post-exposure observations. : Clinical Observations at the TimeofBody Weight Determination ``Tehxeproesuwreergernooupadatvetrhseetoirmetoesftbsoudbsytawnecieg-hrteldaetteedrmcliinnaitciaolns.igAnlslocfltinoixciaclitsyigonbssoebrsveerdveind awneyre `common in this strainofrat. Clinical Pathology Evaluation A. Hematology and Coagulation (Table 10-11, Appendix F) There were no treatment-related rats exposed to H-25134. or statistically significant changes in hematologic perameters in B. Clinical Chemistry --_ (Table 12, Appendix F) CMheoalenstcehroollescteornoclenctornacteinotnrawtaisonmi(l3d3lmygd/edcLr)eaisnedthiisn mgarloeusp ewxapso6se9d%tooft1h0e0 mcogn/tmr?olagtrtoesutpdmaeya2n5. (48 mg/dL). Cholesterol concentration was also minimally decreased (change in mean not statistically significant) in some males exposed to $or 30 mg/m'. Decreased cholesterol was considered to be potentially adverse at 100 mg/m', due to the magnitudeofthe change. After 31 daysofrecovery, cholesterol concentrationsofrats previously exposed to H-25134 were similar 10 control group values. `There were no other adverse changes in clinical chemistry parameters in male rats exposed to H-25134. The following statistically significant and/or treatment-related change in mean clinical chemistry parameters were considered to be non-adverse or not related to exposure to the test compound: + Tsirgingilfyiccearnitdeosnlwyerinemmailledslyedxepcorseeadsetod 5ion rma3l0esmge/xmp'o)s.edAtloth5,ou3g0h, otrhe1se00chmagn/gems (sshtaotwisetdiacalfllyat concentration response (S35, 64, and 75% of control group mean, respectively), they were considered to be treatment-related due to the consistencyofthe response. However, the changes were not considered 10 be adverse, because mildly decreased triglycerides concentrations are not associated with adverse effects. After 31 daysofrecovery, triglyceride `concentrationsofrats previously exposed to H-25134 were similar to control group values. Company Sanitized.DoesnotcontaininTSTSCA CBI -= H-25134: Four-Week Inhalation Toxicty Study inMale Rats DuPont-11414 ~ tTohbeefounlrleolwaitnegdsttoateisxtpiocsalulryestiogntihfeictaenstt cchoamnpgoeusnidn cbleicnaiucaslecthheemrieswtarys pnaoracmonecteenrtsrwaetiroenc-ornesspiodnesreed relationship. + Minimally decreased inorganic phosphorus in males exposed to 30 mg/m? + Minimally increased chloride in males exposed to 5 mg/m? C. Urinalysis (Table 13, Appendix F) There were no treatment-related changes in urine volume. D. Plasma and Urine Fluoride (Tables 12-13, Appendix F) (Esxtpatoissutircealtloy sHi-g2ni5f1i3c4antcaounsleydaitn1cr0e0amsge/dmm'e).anIunrcirneeasfelduomreidaeninurmianleefslueoxrpiodseeidndtioca3t0esorex1p0o0sumrge/mto? `iasnodlatmieotn.aboAlfitsemr 3o1fadafylsuoorfirdeec-ocvoenrtayi,niunrginmeolfleucourlied,esawnedries csoinmisliadreriendaltlogbreounposn,-aidnvcleurdsiengin controls. --~ E. Conclusions dIenccroenacsleussiionns,eerxupmoschuorleeosftemraoll.e Trratesattome1n0t0rmegla/tmed? bHu-t2n5o1n3-4adrveesruslteecdhiannpgoetsenitnicalluldyeaddvmeirlsdelymild dfleucorreiadseeidnsmearluems terxipgolysceedritdoes30inomra1l0e0ramtgs/emx'p.osAefdetro351, 3d0a,ysoorf10re0cmovge/rmy?,,saenrdumincchroelaessetderuorli,ne csoenrturmoltrgirgoluypcerviadleuse,s.and urine fluorideofrats previously exposed to H-25134 were similar to tThheerneof-oardev,erusned-ecrfftehcetcloenvdeiltfioornsmoafltehirsatsstwuadsy a3n0dmfgor/tmheHc-l2i5n1ic3a4l,ptahtehohlioghgeysptaerxapmoestuerres mineatshiusred, study. Blood Fluorine Analysis A. B(Tlaobolde F1l4,uoArpipneenAdniaxlyGs)is --_ eBxlpooosdefdlutoor3i0nemcgon/cmentornattiesotndwaays2s5l,iaghntdlyiinnrcartesaesxepdoasbeodvteob1a0c0kgmrgo/umn'd ocnontceesnttdraaytsio7n,i1n4r,aatsnd 25. ~ ~~ ~27- CompanySaniizeq, Dows notcontaiTnoca cay H2-255113344: FFoouurrW-WeeeekkIInnhhaallaattiioonnTTooxxiiciityySSutuddyyiinnMMaaleeRRaattss______ DuDubPoonwt-i1d14t14d ~~ cHoonwceevnetrra,tioonnsteisnt draalys 5e4x,pofsoelldotwoin5g, a30p,proorxi1m0a0tmelgy/ma?onwee-rmeosnitmhilraerctoovetrhey cpoenrtiroodl, bvallouoed. fTluhoeritneest scounbcsetnatnrcaetcioonntiasincsonfsliudoerriende itno tbheeachmeamrikcearlofsterxupctousruer,ea,nadntdhewaisncrneoatsceoinnsibdleoroeddftlouobreinaedverse. Anatomic Pathology Evaluation A. Mortality There were no test substance-related deaths in this study. B. Organ Weights (Tables 15-16, Appendix H) A3b0saonldu1te00anmdgr/emla'tigvreotuopsbraatinthmeeianintihaelasratcrwiefiicgeh.tsTwheerree wsiegrneifniocatnetsltysluobwsetarntchea-nrtelhaetceodntgrrooslsionrthe microscopic effects in the weights in these groups. heart. This weight change was attributteod lower mean final body --_ Absolute and relative the 100 mg/m? group, to brain and the mean thymus weights relative to body mean were significantly higher than the thymic weights were significantly control higher in tbrhaainn)thaencdonatbrsoolluitneamlletaesntweexipgohstusreoftgrhoeuptshyatmutshewienriteialloswaecrriftihcae.n cTonhterorleslaitnivtehe(t3o0baonddy and to m1i0c0rmosgc/omp?icgrefofuepcstsatinthteheretchoyvmeursy astaceriitfhiecre.tiTmheerpoeinwte,raenndothteesrteswuabsstnanoccel-eraerlactoendcegnrtorsastoiron sraeclraitfiiocneshainpditnhtehnelwoewiegrhtateftfheectr.ecTohvuesr,y stahcirsiffliucce)tuwataisoncoofnstihdeyrmeudstwoebieghstpu(rhiioguhse.r at the initial `eTxhpeosreulraetigvreotuopbsoadythmeeiannititaelstseascrwiefiicgehtasndwewreeresiagtntirfiibcuatnetdlytohilgohweerrtmheananthfeincaolntbroodlyinweailghtetsst in these groups. Tthhee1r0e0lamtigve/tmo bgrooduypmaetatnheadinrietniaallswaecriigfhicte.waTshseighniigfhiecarnmtleyahnigahderren(asltawtiesitgichatllwy)asthparnimcaornitlroyldiune tm0e.aannuandurseunaalllwyehiigghhtwientighhet0(00.1m12g/mg)?imnaolnees awnaismacoln(s6i6d4e8r6e0d)t.obTehussp,urhiioguhse.r rTehlaetiavbesotolubtoedaynd raedlraetniavle wteoibgrhatisn,imnetahen3a0draenndal1w0e0igmhgt/smi'ng1r0o0upmsgw/ermeasniigmnailfiscaanntdlythheigmheearnthraenlatthievecotnotbroodlya,t the rateceoitvheerryssaaccrriiffiiccee.anTdhethreemwaegrneitnuodgeroofstshoer mweiicgrhotsdciofpfiecrteensctessubwsetraencsemaelflf.ecTtsheinatdhreenaadlregnlaalndg,laansd. dinocroetahseer ionrgbaondsy, wweoiuglhdt.beInexcpoemcptaerditnogionrcgreaansewesilgihghttslyfrinowmeciognhtrtoalsaynoimuanlgsainnimthaelsignirtioawlaanndd ~~ recovery sacrifices this is indeed the fact, except for the adrenal gland, which actually had a 3 CompanySanWmd DOSTGOMATSCATE! 125134:FourWeek Inhalation Toricity Sudy in Mal Rats DuPont 11414 ~ (l0ow.e0r5m5eVaSn 0a.b0s5o1l8u)t.e wTehiugsh,ttihnersteactoivsetircyalcloyntsrioglnsiftihcaanntiandtrheenaylouwnegieghrticnihtaanlgseascriinfi3c0emcgonmtrolasnd biinol1o0g0icmagl/lym'imrpeocrtoavnetr,y animals were considered to be spurious and not test substance related or `rTehceovreelraytisvacertiofibceo.dyT,hmeeamangkniidtnuedyeowfeitghhetcwhaasngseigwniafsiceaxnttrlyemheilgyhemriniins1c0u0lemagn/dm?thearneimwaelrseantothteest substance-effects in the kidney. Thus, this weight change was considered to be spurious. There were no other significant organ weight changes at either time point. C. Gross Observations (Tables 17-18, Appendix I) Gross observations noted were sporadic across groups and were not test substance-related. D. Microscopic Findings (Tables 19-20, Appendix I) Squamous metaplasia/hyperplasia of the ventral pharyngeal mucosa was observed at al exposure ~~ TcohnicselnetsriaotniownassofliHm-it2e5d1i3n4lioncaitniitoinaltosaacrviefriycesmaanlilmaalnsdasnpdecwiafisccpoonrstiidoenorefdthteestvseunbtsrtaalnecpei-grleoltattiesd. aalnwdawyasspreexsternetmienlythmeisnliimdaesl eixnaimtis neexdte,ntwhaincdhsaecvecroiutnyt.s Tfhoretshpeecaipfpiacrelonctaltioowneorfitnhceidleenscieoonfwtahsisnot elexspioosnuirne tghreouhpisg,hecsittheexrpionsuirnecigdreonucpe.orThseevreeriwtay,s innodiacpaptairngentthactonaclenetxrpaotsiuornerceosnpcoennsteraatciroosnss. were above the iritant threshold for this substance. This lesion was not present in recovery animals, indicating reversibility of the lesion. Squamous metaplasiaofthe ventral laryngeal mucosa in rats is a common, nonspecific response to irritants and represents replacement of normal pseudostratified epithelium with squamous epithelium. This squamous epithelium is indistinguishable from that which normally lines other areasoflarynx. Squamous metaplasiaofthe larynx occurring absent more severe changes, such as keratinization or ulceration, s generally considered an adaptive response where one epithelial `tmyipneiimsalreapnldacfeodcably, armevoerrseibrlees,isatnadntnootnea.ss*o'c*i'at9edInwitthhe portehseernhtissttouldoyg,icsaqlucahmaonugsesm.etTahpelraesfioarew,as these changes can be regarded as adaptive andofequivocal toxicological significance. Other microscopic observations noted areknownto occur spontaneously in rats of this strain and age and were not present in a concentration response fashion in either incidence or severity. --_-- `Company Saniized. Docs not containTSCACBI H2H821531346:: FFoouurrW-Weeeckk nobblaaaoonnTTorivcietyySStuuddyyiinnMialleeRaRtass__ ~ E Conclusions puDuppoomneci11n4a1i4a THh2e5r1e3w4e.re no compound-related mortality, organ weight, or gross findings in ats exposed to TmehteapNlOasEiaLrhfyoprearnpaltasoimaiocfptahtehoplhoagryynwgaesal1m00ucmogs/ama.t aTlheexmpoisnuirmeallemvieclsrorsecporpeiscenstsquaacmoomusmon aLdaarpyinigveealressqpuoansmeoutso amnetiarpiltaasnitaesxwpoassunroetapnrdesiesontfeinqurievcoocvaelrytaonxiicmoallosgiicnadlicsaitginnifgirceavnecres.ibility of the lesion. --_ ~~ _-- Company Saritized. Does not contain TSCA CBI 125134:FourWeek Inhalation Toxicity Study in Male Rats --~ DuPont11414 CONCLUSIONS Test substance-related, statistically significant decreases in body weight gain and food efficiency occurred in rats exposed to 30 or 100 mg/m'. Although slightly decreased body weight gain for rats exposed to 5 mg/m? also appeared 10 be test substance-related, it was not considered to be adverse since the mean body weights were only 4.3% lower than the control value. Unscheduled mortalitydid not occur during the study. Incidencesofclinical signs following exposure and at the timeofbody weight determination were similar for all groups. Cholesterol concentration was mildly decreased in males exposed to 100 mg/m at test day 25; these changes were considered to be potentially adverse. After 31 daysofrecovery, cholesterol concentrations for al test groups were similar to control. Triglycerides were mildly decreased in males exposed to 5, 30, or 100 mg'. Although these changes showed a flat concentrationresponse, they were considered to be test substance-related. However, the mildly decreased concentrations were not associated with histological changes, and therefore, they were not considered to be adverse. After 31 daysofrecovery, the triglyceride concentrations for al test `groups were similar to the control values. Blood fluorine (but not plasma fluoride) concentration was slightly increased above background concentration in ats exposed to 30 or 100 mg/m'. Urine fluoride was also increased in rats exposed to 30 or 100 mg/m'. At the endof the one`month recovery period, blood fluorine concentrations and urine fluoride amounts were similar to control. There were no other treatment-related changes in clinical pathology parameters for any 0 testeroup. Statistically significant changes in organ weight and relative organ weight (relative to body weight or brain weight) that were secondary to decreased body weight occurred in the heart and testes. Squamous metaplasia/hyperplasiaofthe ventral laryngeal mucosa was observed in rats exposed 10 5, 30, or 100 mg/m' at the sacrifice on test day 25. The lesionwas minimal, focal, and not concentration-related with respectot incidence or severity. Squamous metaplasiaofthe ventral larynxofrats is a common, nonspecific response to irritants and is generally considered `an adaptive response. This lesion was not present in animals sacrificed after a one-month recovery. `The no-observed-effect level (NOEL) for this study is defined as the highest concentration at which toxicologically important effects attributable to the test substance were not detected. Thus for this study, the NOEL is equivalent to the NOEL as defined by the United States Environmental Protection Agency (1985), and the no-observed-adverse effect level (NOAEL) as defined by the European Union (1994). Under the conditionsof thestudy, the NOEL was. 5 mg/m based on decreased body weight gain at 30 mg/m* and above. The minimal `morphological changes in the larynx obsertved at all exposure concentrations were considered to be a nonspecific, adaptive response and isofequivocal toxicological significance. ~ `CompanySani.Dossnotcontain TCAGy I H21925113344::FFoouurrWWeeeekkInIhnhaallaattiioonnTTooxxiicciittyySStuuddyyiinnMMaelleeRRatass ~ RECORDS AND SAMPLE STORAGE DuDPupoonntti11i4d1i4a Atlhle sdpaotnasaonr.d rLeacboorrdastofroyr-asnpaelcyitfiiccalorchsairtaec-tsepreicizfaitciornaswcodantdau,cstuecdhbaystpheerssopnonneslorfiwlielslabnedreeqtuaiinpemdenbty records will be retained by the facility where the work was done. ALabsoarmaptloeroy,ftNheewatrekst,sDueblsatwaanrcee.wilSlpebceicmoelnlse(ctiefdapfpolriacracbhlie)v,e purposes raw data, and and retained the final at Haskell report will be retained at Haskell Laboratory, Wilmington, Delaware. Newark, Delaware, or at Iron Mountain Records Management, REFERENCES 2. Calculation described in Sierra Instruments, Series 210 Ambient Cascade Impactors and Inc., Bulletin 7-79-219IM, Cyclone Preseparators. Instruction Manual: 3. DWrialpeeyr,,NNe.Rw. Yaonrdk.Smith, H. (1981). Applied Regression Analysis, 2** edition, pp 266-273. fs 4. Selwyn, MLR. (1995). The useoftrend tests o determine a no-observable-effect evel in animal safety studies. Journal of the American Collegeof Toxicology 14(2), 158-168. 5. Jonckheere, AR. (1954).A distribution-free K-sample test against ordered alternatives. Biometrika 41, 133-145. 6. Levene, H. (1960). Robust test for equalityofvariances. Contributions to Probability and Statistics (1. Olkin, ed.), pp 278-292. Stanford University Press, Palo Alto. 7. Shapiro, S.S. and Wilk., M.B. (1965). An analysisof variance test for normality (complete samples). Biometrika 52, 591-611. 8. S34n9e-d3e5c2o.r, TGh.eW.Ioawnad SCtoactherUanni,veWr.sGi.ty (P1r9e6s7s),. loStwa.tistical Methods, 6 edition, pp 246-248 and 9. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Amer. Statist. Assoc. 50, 1096-1121. 10. Kruskal, W.H. and Wallis, W.A. (1952). Use of ranks in one-criterion analysisofvariance. J. Amer. Statist. Assoc. 47, 583-621 11. Dunn, 0.3. (1964). Multiple contrasts using rank sums. Technomerics 6, 241-252. ~~ Company Sanitized. Dos not contain TCA cy --- H2e325113344:: PFoouurr-WWeeeekkInIhnhaallaattiioonn TToonxiicciittyySSttuydyiinnMMaalleeRRatess DuDPuopnontti1l1d4l1d4 ~~ 12. Fisher, R.A. New York. (1985). Statistical Methods for Research Workers, 13" edition. Haffner, 13. Lewis, DJ. (1991). Morphological Toxicol. Pathol. 19(4 P11), 352-357. assessmentof pathological changes within the rat larynx. 14. Burger G.T, Renne R.A, Sagartz A.W. (1989). Histologic changes J.W., in the Ayres P.H., Coggins C.R., Mosberg A.T., respiratory tract induced by inhalation of and Hayes xenobiotics: physiologic adaptation or toxicity? Toxicol. Appl. Pharmacol. 101(3), 521-542. 15. Kilgour J.D. Foster J., Soames A., Farrar D.G., and Hext P.M. (2002). Responses in the respiratory tractofrats J. Appl. Toxicol. 22(6), following 387-395. exposure to sulphuric acid aerosols for 5 or 28 days. -- -- -ms Company Sanitized. Doos not contain TSCACBI --_ B21255113366FFoouurrW-WeecckkIInnbhaallaitoinonTTonoiicySStuuddyyiinnMMaalelReaRtsats____ bDuubpooneniti1a1t41e4 -- TABLES ~ rr Company Sanzod.903Doo, notconTtsaingy 12125511336:6FourWeek nIbnahlaluattiioonnTTroiicktySSutuddyiinn Matle Rattss -- TABLES ABBREVIATIONS: EXPLANATORY NOTES CChhaammbbeerr CEonnvciernotnrmaetnitoanls CoofnHd-i2t5i1o3ns4 S.D. - standard deviation SEM. - staern rordofa ther med an mg/m' - millpiergcurbiac mmetser n - numofbsae mplres Summary of Hematology Values RBC - redblco ello coudnt HGB - hemoglobin HCT - hematocrit MCV - mean corpuscularvolume MCH - mean corpuscular hemoglobin --_ MCHC - meancorpuscular hemoglobin concentration RDW - redcell distribution width ARPELTT -- plaabtseolleuttecroeutnitculocyte count AWNBECU -- wabhsiotleub te nl eucto erloplo hcioludnaltl forms) ALYM - absolute lymphocyte AMON - absolute monocyte AEOS - absolute eosinophil ABAS - absolute basophil ALUC - absolute large unstained cell Summary of Coagulation Values APTPTT -- pacrtoitvhartoemdbpairntitailmethromboplastin time DuDbuoponnctii11d4i14s -- _-- Companys,i omg "ontain TSCA gy 2112255113344:FFoouurrWWeeeekkInIhnahlalaattiioonnTToonxiicitySSutuddyyiinnMMaaleeRRaattss __ --_ TABLES DDuubpoownet11i1d4i14s. EXPLANATORY NOTES (Continued) ABBREVIATIONS (Continued): SummaryofClinical Chemistry Values AST ALT -- aaslpaanritnaetaemaimniontortarnasnfsefrearsaese. SDH ALP - sorbitol alkaline dehydrogenase phosphatase BILI - totalbilirubin BUN - ureanitrogen CREA - creatinine CHOL - cholesterol TRIG GLUC - tgrliugcloysceerides ALTBP - toatlablupmriontein GLOB - globulin ~~ CIAPLHCS - icnaolrcgiaunmic phosphorous NA - sodium K - potassium CL - chloride PLU - plasma fluoride Summary of Urinalysis Values UOVSOML - uvroilnueomsemolality pH. URO - tuhreobliolgianroigtehnm of the reciprocalofthe hydrogen ion concentration UFLU - urine fluoride UMTP - urine protein Compan Sa01223. 000s not copia Tscacey En H2e525113344::FFoouurrWWeeeekkInIhnhaallaattiioonnToxicity StuudyyiinnMMaaleleRaRtass ~~ DDuubPoonnetl1i14d1i4a e---- TABEL-- EES -- ---- -- NOTES: EXPLANATORY NOTES (Continued) Chamber ConcentrationsofH-25134 Particle Size Distribution of H-25134 Chamber Environmental Conditions Values are reported to 2 significant figures. Calculations were performed prior to rounding values. Summary of Hematology Values Summary ofCoagulation Values Summary of Clinical Chemistry Values Summary of Urinalysis Values `When an individual observation was recorded as being less than acertain value, calculations were performed onhalf the recorded value. For example, if bilirubin was reported as <0.1, 0.05 was used for any calculations performed with that bilirubin data. --_ ~~ -_-- Company Sautecud. Lous nox comaun 154 gy 121255113344: FFoouurrWWeeeekkInIhnahlaalattiioonnToxxiiciity SSutdyyiinnaMaeleRRatass_ --_~ DDuubponlti1d14i1s4, TABLE 1 CHAMBER CONCENTRATIONS OF H-25134 DESIGN CONCE(mNgT/Rm?A)TION S 30 100 MEASURED CONCENTRATION" GROUP MEAN (mg/m) SEM. RANGE =u [i v 51 31 019 093 37-69 20 20-37 20 vi 100 24 66-120 20 fVailolmeserxepporseusreenshe mean, standard errofthe mean (S.E.M.,an rege ofthe daly mes values obained TABL2E PARTICLE SIZE DISTRIBUTION OF H-25134 DESIGN CONCENTRATION|EXPOSURE| MASS MEDIAN AERODYNAMIC GSETOAMNETDRAIRCD]| 9% PARTICLES __BY MASS ~ (mg/m5 NUMBER 4 [DIAMETER 37 (um) DEVI1A6TION [<1[02pm <334pm <I09 pm 8 30 1s [04 50 100 13 38 6 [02 32 100 17 37 1s [03 3 es 30 3 47 17 [ols 20 93 6 47 17 fo2 2 9% 1 52 19 S123 100 100 126 3497 210s |So11262 9 7 40 31 770 100 2 44 14 S100 100 is 45 16 > 13 9 EE e (Company Suuzea. uous not coman 15GAcar ~ i _ !8 3 | 5 2 z3 :=3 ~ i& dsess8s%a Sess sf i Solslan-g 23E5F5S58gs8 = <2 & SH mezs I 2 g [E [Eless i gE [5lwad 5 E 82g |Z g2xoEd83=c=ePn2Ys3| g 2E ow a58 [Ezese FRECHE s fEE 1 2 5sg g[2 [|SZ|faAeaRaAas8 2=2 zc 2[E. 058ss 3I I7 EER gIz =azn id g : Ei i g El E" z5 SAEgE sg i 1E Z8 z, :: ' COMPANY Gv es is cua soc 22H-321513344: FFoouurr-WWeeeekkInIhnhaallaattiioonnTTooxriicciittySStuuddyyiinnMMaalleeRRaattss --~ TABLE4 MEAN BODY WEIGHTS OF MALE RATS DAYSONTEST ___ Group T 0mg/m' MEAN BODY WEIGHTS (g) Group Ill Group V 5 mg/m' 30 mg/m EXPOSURE 0 27155 13.2015) 2721 14.3(15) 2734 13.905) 7 3047 2958 29538 21315) 183015) 189015) 14 3332 3207 3148 268(15) 21.705) 228015) 21 3582 3453 3336 314015) 253015) 27815) oo 25 3437 3290 3152 34510) 26.910) 289010) DuDbuoPnoenltl1a1l41s4 Group VII 100 mg/m? 2717 15.6015) 2949 245015) 3186 29.4015) 3407 33.0015) 3233 35.6(10) -- Company Santitad. Doss not contain Tscacer EE H:25134: FourWeek Inhalation Toxicity Stay in Male Rats -- DuPont 11414 TABLE 4 (Continued) MEAN BODY WEIGHTS OF MALE RATS DAYSONTEST RECOVERY 23 35 2 Group | 0 mgm' 3599 21.25) 397.4 3065) 4306 24.405) MEAN BODY WEIGHTS (2) Group IIT Group V 5 mg/m' 30 mg/m 3468 15.4(5) 3869 18.965) 4144 19.165) 3503 20.15) 3929 2076) 4268 22.15) Group Vil 100 mg/m' 3570 32765) 3952 36205) 4292 40.065) 4 4604 4389 4560 4345 21.405) 22405) 275) 47165) --_ 56" 441.1 4221 439.7 4416 21.05) 2156) 27165) 46.0(5) Damamangedas: SMteaanndard deviation (Numberofvalues included in calculation) "There were no satsticll significant differences from control at p < 0.0. a Weight losses due o fastingofrats prior o clinical pathology evaluation. - Company Sanitized. Doss not contain TSCA cay H2H5L21813544::FFoouurrWWeecekkinIhnahlalaattiioonnTTooxcsttySSudtyiuinMMdaatlyeeRRaattss --_ DDuuppoonneci1n4a1n4e TABLES DAYSONTEST EXP0O-S7URE 7-14 MEAN BODY WEIGHT GAINS OF MALE RATS Group MEAN BODY Group IT WEIGHT GAINS Group V (2) Omg' S mg/m' 30mg' 2110.2605) 277505) 263.415) 2789505) 2693015) .6130#15) 1G0r0oumpgVImI 2115.20015) 232..670#15) 14-21 295.04(15) 256705) 168.980415) 2554015) 21-25 "16858(10) 2445010) "19s.44(10) 473s330) A RE2C8O-V3E5RY 376 01 as 381 14365) 476) 666) 755) 35.42 31110165) 2872s05) 35976) 3543005) 42-49 209 5365) 27s06) 272.665) 2850305) 49-56" 133456) "168 336) 4163 406) "129 6165) -- cOmPany Sani1200. Dogs, notcontain Ta cg = --- H:2255113344::FFoouurr-WWeeeekkIInnhhaallaattiioonnTTooxxiicciittyySSutuddyy iinnMMaalleeRRaass_ --_ DuDPuoPonnlt1-d1144i1d4. TABLE $ (Continued) MEAN BODY WEIGHT GAINS OF MALE RATS DAYS ON TEST Group T Omg/m MEAN BODY WEIGHT GAINS (g) Group Ill Group V 5 mg/m 30 mg/m? Group VII 100 mg/m' OVERALL 0-25 69.0 21.9(10) 564 167(10) 39.6% 15.8(10) SLs# 21.110) 28-56 872 754 89.4 845 16.0(5) 11365) 17.165) 20.15) 0-56 1700 1511 1706 1702 23.75) 14.6(5) 2.165) 38.3(5) --_ Dunarmngedas: Mean Standard deviation (Numofbvaelures included in calculation) # Sutisicall significant difference rom control at p < 0.05 by Jonckheere Terpstra trend fest. a Weight losses due to fastingofrats prior o clinical pathology evaluation. --~ `Company San'tized. DoesnotcontainTSCA Cay a LHLe225511334%:: FFoouurrWWeeeekk IInnhhaallaattiioonnTTooxxiicciltyySSutuddyyiinn MMaalleeRRaatss __ DuDPupoonnttl1i1d4l1s4, TABLE 6 MEAN DAILY FOOD CONSUMPTION BY MALE RATS DAYSONTEST MEAN DAILY FOOD CONSUMED PER ANIMAL (g Group I mgm `Group IT 5 mg/m Group V. 30 mg/m? Group VII 100 mg/m EXPOSURE 7 26 23015) 241 1715) 08 1.905) 27 27(15) 14 23 26015) 2.1 1705) 26 18015) 23 21015) 2 24 29015) 24 2.1015) 25 20015) 207 19015) OVERALL mn 0-21 24 22 20 26 2378015) 1.688(15) 1.727015) 2052015) Dusomnged as: MSteaanndard deviation (Number of values included in calculation) There were no iatisteally significant differences rom contol tp < 0.05. ~~ `Company Sanftzed. Does not contain TSCA cal TT 121525113344::FFoouurrWWeeeekk IInnhhaallaattiioonnTTooxrieitcySSttuuddyyiinnMMalleeRRaattss ~~ DuDPuopnocnltid11l41s4, TABLE 7 MEAN DAILY FOOD EFFICIENCY OF MALE RATS DAYSONTEST (2 WMEEIAGNHTDAGIALIYN/FgOFOODOEDFCFOICNISEUNMCEYD) Group 1 0 mg/m Group II 5 mg/m' Group V 30 mg/m? Group VII 100 mg/m EXPOSURE 0-7 0.167 0035015) 0.139 0.038015) 0133 0.033(15) 0.35 0056(15) 1 0.165 0.03515) 0.147 0.033015) 0.119% 0.03615) 00..104339415) 2 0.144 0.04615) 0.143 002515) o.18# 0.04015) 0.132 0.027(15) ~ OVERALL 0-21 0159 0.143 0.123 0.138% 0.03115) 0025(15) 0.030015) 0.032015) Data amnged as; `MSetaanndard deviation (Numofbvaelures inched in calculation) # Statistically significant difference from control at p < 0.03 byJonckheereTerpstra rend test. --~ -_-- Company sa"zed. Does not contain Ta gy ~z i z ~ : 2| 2 Z| 5 3i ~i E 3E34 a a8 aBE :OE = 8 Bgg Ee "x -3 -& ca s- $ x= [[5B2ES =st =et Egm 2egy =a= . H |. 3Ri8l8 fl3g4 EE Eg 285] = or "gx -g -a| di: =Zz 3E8g8e &2 gz. @ sig: Ig 2 | a -~3 -a ~a oi : A z33| S33 5Z = < z 7 B54%rSs 5o43&fpaf&43 4o3n& 4op3f]l i & 4 iF 2 Bio: 2i555%d23 iif 2 553 = "ii E5:8 C CompanySenitized.Doesnot, rots ~ 33 4 --_ 4 32z 2;Z 53: =1 i2 =| == : to ss g gFl288%e7 g8 g a= = g IL 8gI. z 5 ER LAE .3 22 _ 3si3g = 5 SZEPPIS)EEE=e == gl a 2iy3d5 $y TLE 5 5gZl| 2QO i8:5 = Hd :zz % 3 35 |#S52:331%= gg JER87,3gE | 25G8ik;r :2 SBigf yi2! 2i5%f a = CompanySatied. Doo otcontainTSCACat H-25134: Four-Week Inhalation Toxicity StianMayle Rats ~~ Dupont11414 TABLE 10 SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group 0 mg/m Group III 5 mg/m Group V 30 mg/m Group VII 100 mg/m? RBCDA(xY102%5uL) 793 785 8.13 795 HGB (g/dL) 0.26(10) 0.289) 0.3610) 025010) DAY 25 157 157 158 157 HCT (%) 0.4(10) 0.40) 0.5(10) 0.610) DAY 25 46.1 456 460 459 Mev @) 13(10) 119) 14010) 1700) DAY 25 581 S81 566 517 1.4010) 1909) 15010) 1.6(10) MCH (pg) ~ DAY 25 198 200 0.510) 0.609) 195 0.610) 198 0.7(10) MCHC (gL) DAY 25 341 343 344 342 RDW (%) 0.510) 060) 0.510) 0.6(10) DAY 25 109 0.310) 108 050) 10 0.4(10) 107 0310) ARET (101) DAY 25 1695 46.6(10) 1752 3100) 1340 35.0010) 1495 21.700) PLT x10%L) DAY 25 1207 1261 100 133 136(6) 1344) 159(5) 1008) WBC (x10) DAY 25 11.48 12.08 1221 1227 ANEU (10%) 2.55(10) 15509) 28510) 271010) DAY 25 149 1.57 120 129 0.60(10) 0.659) 0.47010) 0.3510) ALYDMAY(x2150%L) 9.50 10.06 1046 1051 --_ 205(10) 1470) 227010) 2.66(10) TTT TSE bo orm sca omy 125134: FourWeek Inhalation Toxicity Study in Male Rats --_ DuPont 11414 TABLE 10 (Continued) SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group1 0 mg/m? Group Ill 5 mg/m' Group V 30 mg/m Group VII 100 mg/m? AMON (x10%uL) DAY 25 AEOS (x10) DAY 25 ABAS (x10uL) DAY 25 ALUC (x10) DAY 25 025 0.11010) 009 0.05(10) 007 0.0310) 0.08 0.02(10) 021 0.0809) 0.09 0.029) 007 0.039) 008 0020) 022 0.12(10) 0.10 0.06(10) 0.09 0.05(10) 013 0.12(10) 022 0.13(10) 0.09 0.05(10) 0.08 0.04(10) 0.08 0.06(10) ~~ Dusarunged as; SMteaanndard deviation (Numofbvaeluers included in calculation) "There werneo siatistcally significant differences from control at p<0.05. --_ Company Sanitized. Does not contain TSCA CBI = -_-- 121255113346: FFoouurrWWeeeekkInIhnahlalaattiioonnTTooxxiicciittyy SStuuddyyiinnMaalleeRRaattss_ -- DuDubpoonnetl1i14d1i4s TABLE 11 SUMMARY OF COAGULATION VALUES FOR MALE RATS Group 0 mg/m? Group III 5 mg/m Group V. 30 mg/m* Group VII 100 mg/m' PT (seconds) DAY25 APTT (seconds) DAY 25 15.7 1.410) 20195010) 16.1 2.110) 201.58010) 155 0.8(10) 191..9710) 154 0.410) 1L967(10) Damamngedas: SMteaanndard deviation (Numberofvalues included in clclation) "There were no stisically significant differences from contol at p< 0.05. -- ~~ _-- ComDany Sanizgg,"Does not contain TSCA cay 125134: Four-Week Inhalation Toc Sudiyn ale Rats Dupont 11414 TABLE 12 SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS Group I 0 mg/m Group Ill 5 mg/m Group V 30 mg/m Group VII 100 mg/m* AST (UL) DAY 25 103 100 109 101 ALT (UL) 19(10) 11(10) 1409) 13(10) DAY 25 31 33 36 35 5(10) 5(10) 89) 7(10) SDHDA(UY/L2)5 124 127 13 131 5.4(10) 5.07) 5.3(8) 4.409) ALKP (U/L) DAY25 197 215 174 213 34(10) 28(10) 3109) 40(10) BILI (mg/dL) --~ DAY 25 0.08 0.08 0.10 0.08 BUN (mg/dL) 0.0310) 0.03(10) 0.039) 0.03(10) DAY 25 15110) 151010) 151010) 12400) CREA (mg/dL) DAY 25 032 031 0.33 0.33 CHOL (mg/dL) 0.05(10) 0.07(10) 0.05(10) 0.05(10) DAY 25 48 43 "4 3 DAY 56 7(10) 52 9(10) 52 9(10) 51 10(10) 51 TRIG (mg/dL) 8(5) (5) 13(5) 18(5) DAY 25 36 11(10) 20* 9(10) 23 609) 27 6(10) DAY 56 51416) 235025) 2641(5) 26440s) _ Company Ss,alized: Dossnot conan 15 cay EE ~~ H25134: FourWeek Inhalation ToxicityStudyinMsleRas DuPontlidld. TABLE 12 (Continued) SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS 0Grmogump!? G5rmogu/pmI?t Gromugp mV 1G0r0oumpgVmI'I GLUDCAY(m2g5/dL) 58 2 2 91 TP aL) 5010) 15010) 7010) 1130) DAY 25 0260310) 61 03010) 64 030) 62 0.410) DAY 56 602665) 60366) 60316) 603565) ALBDA(gY/dL2)5 43 43 44 a2 DAY 56 4022(10) 0240410) 0a220) 4022(10) GLOB (gL) 0165) 0265) 0265) 026) Si DAY 25 0210010) 011810) 20026) 0220010) DAY 56 24 0265) 02225) 02126) 201365) CALDCAY(mg2/5dL) 108 108 106 107 IPHS (mg/dl) 0.410) 02010) 0.410) 04(10) DAY25 9096010) 9056(10) 087701@0) 9100310) NAD(AmYol2l5) 1469 147.4 1484 1492 K (mmol) 15010) 21010) 24010) 26010) DAY 25 053957(10) 06504910) 5.89 0410) 589 021010) --~ -_-- `Company Sanitized. Does not contain TSCA CB He25134; Four-Week Inhalation Toxicity Study in Male Rats -- DuPont 11414 `TABLE 12 (Continued) SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS Group 1 0 mg/m' Group Ill 5 mg/m' Group V 30 mg/m? 1G0r0oumpg/VmI?I CL (mmol/L) DAY 25 PFLU (ng/mL) DAY 25 1020 1.6(10) 8) 0.0010) 104.0 22(10) 0.1 0.1010) 1023 1.4010) 01 0.010) 103.3 18010) 01 0.009) Dawamngedas: `MSetaanndard deviation (Numofbvaelure included in calculation) @+ SStsatiicstaiclalllyy ssiiggnniiffiiccaanntt ddiifffferreennccee ffroomm ccoonnitrrooll aattpp << 00..0055 bbyyDDuunnnesttfeTta.rhane-Dunnett est. -- ~ --_-- Companny y Sanittized. Does not contain Tsca gy 12H:821513344;:FFoouurrWWeeeekkiIanlhaaltaitoionnTTooxxiicciittyy SStuuddyyiinnMMaalleeRRatass__ -- DuDuPPoonntti1i1d41i4s TABLE 13 SUMMARY OF URINALYSIS VALUES FOR MALE RATS Group 1 0 mg/m' Group Ill S mg/m' Group V 30 mg/m* Group VII 100 mg/m? VOL (mL) DAY 25 62 56 48 66 UOSM (mOsm) 4.610) 3610) 2810) 4.4010) DAY 25 1547 964(10) 1330 859(10) 139 848(10) 129 692(10) oH DAY 25 61 69 66 65 0.5010) 0.5(10) 0.5(10) 0.510) URODA(YBU2/5L) 02 02 02 02 UFLU (ng) 0.0(10) 0.0010) 0.0010) 0.010) --~ DAY 25 132 128 186 29 3.00) 5.109) 528) 8.4(8) DAY 56 147 130 17 139 5065) 3365) 2005) 3.55) UMTP (mg/dL) DAY 25 129 102 86 75 72010) 72(10) 62(10) 66(10) Daamngedas: SMteaanndard deviation (Numberof values included in calulaion) * Statistically significant diffrence from control tp < 0,05 by DunnetTambane-Dunnet test. CompanySanitzed.Dossnot conTtsaicany I -------- 12255113344::FFoouurrWWeeeekkInIhnahlalaattiioonnTTooxviiciityySStutdyiuinnMdMalyleeRatss --~ TABLE 14 SUMMARY OF BLOOD FLUORINE ANALYSIS DAYSONTEST 0Grmogump' BLOOD FLUORINE (ppm) G5rmogu/pmI'l 3G0romugp/mV' 0 0113165) . : 7 01.41165) . . 14 10 . 0.196) * 2 Ll 0.0465) 14 008(5) 25 0244) ~ 54 12 13 18 0.125) 02265) 0.1665) DuDburoonneti1i1a4i1s4. G10r0oumpg/VmIL? 17 02165) 21 0235) 31 07165) 38 05365) 17 0295) Duamngedas; MSteaanndard deviation (Numberofvalues included incalclation) a Samples not evaluated fr tis imepont. --_ `Company Santtized. Does nor contain TSCA cg; ef imot------ 12H255113344:: FFoouurrWWeeeekk IInnhhaalation ToxiceittyySSutdudyyininMMaalleeRaRts --~ DuDbuopwoenltia11t41d4. TABLE 15 MEAN FINAL BODY ANDDAYOR25GSAANCRWIEFIIGCHETS FROM MALE RATS Group 0 mg/m Group IT 5 mg/m' [= 30mgm' Group VII 100 mgm MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) LIVER 9.990 9.607 9.115 9.535 1.280010) 0787(10) 1.031010) 1.27510) KIDNEYS 2921 0.408(10) 2982 034610) 2800 0259(10) 2.966 0361010) LUNGS 01.26091310) 01.617938(10) 0.11.85651(10) 01..168537(10) HEART --~ SPLEEN 1373 021410) 0.583 0.130010) 1.365 0.165(10) 0.606 0072(10) 1.199% 0.116010) 0575 0131010) 1.239% 0.150(10) 0579 0.098(10) BRAN 1.957 1.977 1.964 1.980 0.138010) 008510) 0094(10) 0.086(10) THYMUS 0375 0.099(10) 0.429 005510) 0.402 008210) 0455 0065(10) ADRENAL GLANDS~~ 0.055 0.066 0012(10) 000510) 0.060 001510) 0070 0017(10) TESTES 033.00527(10) 0322451310) 0323552200) 03228551(10) EPIDIDYMIDES Lois 1077 0.10510) 0.195(10) 0979 010100) 1059 0.129(10) FINAL BODY WEIGHT (3g4r3a.m6s9)0 328.990 315200 323340 -- 3454210) 26854010) 2894510) 3559110) --------------Te Comme DoE notcontain TSCA cay 12H5e21531344::FFoouurr-WWeeeekk iInnhhaallaattiioonnTTooxxiiceittyySSudtyiiunnMMdaalyleeRRauts DuDpuoPnoenitid11l41d4, TABLE 15 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 25 SACRIFICE Group 1 0 mgm' Group Ill 5 mgm' Group V 30 mg/m* Group VII 100 mg/m? MEAN RELATIVE ORGAN WEIGHTS ( %ofbody weight) LIVER/ FINALBODY *100 2.906 0.230(10) 202 0.120010) 2.893 0.228(10) 2.948 0.209(10) KIDNEYS! FINALBODY * 100 0.850 0.091(10) 0.905 0.052(10) 0.891 0.080(10) 0917 0.040010) LUNGS! FINALBODY * 100 0492 0.040(10) 0.509 0.046(10) 0.495 0.038(10) 0515 0.053(10) --_ HEART/ FINALBODY *100 0398 0.039(10) 0415 0.03210) 0382 0.03710) 0.384 0.03510) SPLEEN/ FINALBODY * 100 0.169 0.027(10) 0.184 0.014(10) 0.182 0.03910) 0.179 0.02010) BRAIN FINALBODY *100 0573 0.053(10) 0.603 0033010) 0.627 0.049(10) 0.620 0.083(10) THYMUS! 0.108 FINALBODY *100 0.020(10) 0.130 0013(10) 0.128% 0.028(10) 0.141% 0013010) ADRENAL GLANDS/ 0016 FINALBODY * 100 0.004(10) 0020 0.002(10) 0019 0.005(10) 0022 0.00410) TESTES/ FINALBODY *100 0893 0.08810) 0.988% 0.076(10) 1.036 0.111010) 1.009% 0.060(10) EPIDIDYMIDES/ FINALBODY #100 0.299 0.041(10) 0327 0.044(10) 0313 0.041(10) 0330 0.041(10) -- Pen Seized.Doesnot contain Tc gay ee ------ H2H:921513344::FFoouurrW-WeeeskkIInnhhaallaattiioonnTTooxxiicciittyySSttuddyiinnMMaalleeRRaattss _ DuDpuoponnttia11i4d14. TABLE 15 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 25 SACRIFICE Group T 0 mgm' Group TIT 5S mg/m' Group V 30 mg/m* Group VII 100 mg/m? MEAN RELATIVE ORGAN WEIGHTS ( organ to brain weight ratio) LIVER/ BRAIN * 100 510099 485.628 464.261 482222 51485010) 28495010) SLROS(I0) 66.222(10) KIDNEYS/ BRAIN * 100 149.057 150.650 142.608 150.138 16981010) 1401910) 12456(10) 19.996(10) LUNGS/ BRAIN * 100 86.257 6.599(10) 84.461 79.368 7.714(10) 7.616(10) 83.705 8.594(10) HEART/ --_ BRAIN * 100 70019 8.664(10) 68.903 6.147(10) 61.056# 5.645010) 62.623 7.408(10) SPLEEN/ BRAIN * 100 29.690 30582 570710) 2.762(10) 29.226 6.493(10) 29.290 5.02110) THYMUS/ BRAIN * 100 19.188 4.908(10) 21.668 2342(10) 20424 4.02010) 23.031# 3.425(10) ADRENAL GLANDS/~~ 2.819 BRAIN * 100 0.587(10) 3313 0234010) 3.029 0733010) 3.531 0.816010) TESTES/ BRAIN * 100 156.386 164.101 165.435 164.535 1373810) 13377010) 13748010) 16.688(10) EPIDIDYMIDES/ BRAIN * 100 52.166 5.49610) 54384 8.51910) 49.807 4358(10) 53.488 5.963(10) Damaged as: MSteaanndard deviation (Number ofvalues included in calculation) # Satisically significant difference from control at p < 0.05 by trend test Jonckheere-Terpsra). ~~ - CompanySenitized. Doss not cont sca car --_ T H2-2551133o 44: FFon ouurrW-Wei eeekk IInnc hhaallaattiiy oonn ToxiS city Su tudy id n MaleyRatsi __nMuleRDDuubPa oownlt1is 1d4n1d4. TABLE 16 MEAN FINAL BODY ANDDAYOR56GSAANCRWIEFIIGCHETS FROM MALE RATS Group 1 0 mg/m' Group Tl 5 mg/m' [a 30 mg/m Group VII 100 mg/m? MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) LIVER 12.850 0.7395) 11.943 1.666(5) 13.727 1.4435) 13911 3.3875) KIDNEYS LUNGS 3.523 0.3575) 1878 022765) 3423 0.190(5) 2.001 0247(5) 3.635 0.2745) 2.150 0292(5) 3.865 0.565(5) 2076 0.470(5) --_ HEART 1553 0.083(5) 1618 022165) 1.591 0.109(5) 1.701 0.289(5) SPLEEN BRAIN 0.867 0.05165) 2028 0.1385) 0.746 0.108(5) 2113 0.11165) 0828 0.136(5) 2115 0.093(5) 0.859 0.239(5) 2082 0.132(5) THYMUS 0.543 0.056(5) 044 0.11065) 0.418% 0.024(5) 0.408% 0.053(5) ADRENALGLANDS 0.051 0.006(5) 0.052 00115) 0.064 0.004(5) 0.070 0.009(5) TESTES 332 0.298(5) 3452 0.199(5) 3358 0234(5) 3235 02005) EPIDIDYMIDES 1279 0.159(5) 1293 0.056(5) 1379 0.090(5) 1346 0.185(5) FINAL BODY WEIGHT (grams) --_ 447.060 2098705) 422120 21.505(5) 439.700 27.084(5) 441.560 45.978(5) SemanSslssdcborsmorrommTscacer HL25134: Four-Week Inhalation Toxicity Study in Male Rats --~ DuPont 11414 TABLE 16 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 56 SACRIFICE Group | 0 mg/m Group TIT 5 mg/m' Group V 30 mg/m Group Vl 100 mgm' MEAN RELATIVE ORGAN WEIGHTS (% ofbody weight) LIVER/ FINALBODY *100 2874 0.098(5) 2826 0325(5) 3117 0.174(5) 314 0463(5) KIDNEYS/ FINALBODY *100 0.787 0.055(5) 0811 0.018(5) 0826 0.022(5) 0.874% 0.065(5) LUNGS/ FINALBODY *100 0.420 0.044(5) 0474 0.045(5) 0489 0.058(5) 0.466 0.064(5) HEART/ 0.348 0383 0362 0.384 ~~ FINALBODY *100 0.018(5) 0.041(5) 0.0175) 0.038(5) SPLEEN/ FINALBODY 100 0.194 0.008(5) 0.176 0.02005) 0.188 0.030(5) 0192 0.0375) BRAIN/ FINALBODY *100 0.455 0.042(5) 0502 0.042(5) 0.483 0.039(5) 0474 0.034(5) THYMUS/ FINALBODY * 100 0121 0.009(5) 0.107 0.024(5) 0.095% 0.006(5) 0.092 0.007(5) ADRENALGLANDS/ 0.011 FINALBODY *100 0.001(5) 0012 0.002(5) 0.015% 0.001(5) 0.016 0.003(5) TESTES/ FINALBODY *100 0.746 0.08%(5) 0818 0.028(5) 0.766 0.075(5) 0.739 0.089(5) EPIDIDYMIDES/ FINALBODY #100 0.287 0.036(5) 0307 0.008(5) 0314 0.020(5) 0304 0.0195) --~ Company Sanized. Dossnotcontain TSA Gay EE H2-825113344::FFoouurr-WWeeeekk IInnhhaallaattiioonnTTooxxiiceittyySSutuddyyiinnMMaalleeRRaatss___ --~ DDuupPoonnti1i14a1i4s TABLE 16 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 56 SACRIFICE Group T 0 mg/m' Group Tl 5 mgm' Group V 30 mg/m? MEAN RELATIVE ORGAN WEIGHTS ( organ to brain weight ratio) Group Vl 100 mg/m* LIVER/ BRAIN * 100 KIDNEYS/ BRAIN* 100 635.644 520285) 174.355 20.595(5) 568.638 102669(5) 162469 14.2605) 650.438 761525) 172253 16.007(5) 663.344 130.705(5) 184.981 16.942(5) LUNGS! BRAIN * 100 HEART/ - BRAIN * 100 92.982 12.504(5) 76.909 7.4915) 94.718 10315(5) 76.730 11.376(5) 101.597 1182965) 75.287 4756(5) 99.177 18.7385) 81.300 9.197(5) SPLEEN/ BRAIN * 100 43015 5.1745) 35.527 6.596(5) 39.076 576765) 40.855 8.988(5) THYMUS! BRAIN * 100 26875 3.578(5) 21354 4.42405) 19.818# 1.8805) 19.554# 1374(5) ABRDARIENN*AL1G00LANDS/ 2.505 0225(5) 2463 0.43765) 3016 0.28005) 3.355% 0.446(5) TESTES/ BRAIN* 100 164.553 19.967(5) 163.618 102735) 159.371 17.7205) 155.735 12.248(5) EPIDIDYMIDES/ BRAIN * 100 63.089 6557(5) 61.401 5.265(5) 65.401 6.687(5) 64.464 6.055(5) Daaaranged as: MSteaanndard deviation (Numberofvalues included in calelation) # Saisicallysignificant diffrence from control ap < 0.05 by rend test Jlonekeere-Terpstra). Company Sanitized, Does o, 61- Bl ~ z TT TT TT iigZii8gefEn}l 3235 25%9 23%5 3297 32g% 33g% 333% | {igh} 38 82 82 82 33 82 3a | ET TTT TT TTTT TTTie , i{B8i.gEHn|i S3g% S377em 33g% S2g3 32g3 8393 3323 i{d3 z 817% 12. 2. ge oe 2 ge 3s 0% g (Bioi e) SET SET EETTE153 z iE is g2 g | iIEE | (I8M8 SEEEL N i i1283 ~ 8g2 82%7Sn ||| }}i 3jg2aEk fs: Eg2As% || ; iiaiiz :2 SgE i | Hstad 2 gf | ii 7 2 | PPBERE OBB RBOEB ERORBi IN 5 i {FE Bg EOF OE OE OE [gf i z32i 5g2 ~ i | } g 8 IM iLIEgE iiE| BgeI giBBosEl : ge2 se 2 i asBo is es0g% liltcaiiybi {|| 5 |PEERZE BTERR g E EBR 4E G % 42E: 2 1ioiRdE4 Company Sanitized. Does not contain TSCA CB) ~3 : ig7i.RE5E1! 2SF. 22%2 2224 2229 3280 22a8 5ER0 | a EE Te 5gae asas am ae | {giR8s] 2% 27 d9 22 29 2% 33 , i1G8E1ieBuHi] 2S7o 2S7o oSFo gSso gSSo BdoE S2o9 | 18 Ter if i FE E (diemS . 37 37 3% 2% 2% 3% 8% 15% Eo = TTT TTT og iE i58 e ~ tEg55s8E % | |iii 22 28%5 || | 3 &gg8 i i|| o : i i142 Pi5s4 : IEiz IHfaC]d hn 3 g2 L fgogoE poe E og oR gi 3 i PE 8B o8 B88 : i fEogogoroE gobi i3 BPE,ERl EFfEi FiFiRig EiEE Z iE ipknkpepikd . ~3 jp RRR RORORE IGE Company Santized. Does not contain TSCA cat ~3 3 z ~ 2 3: 3 : 3ii Z 2i Eigi8TpE| TE% n82 e82 e22 32 32 32 | E{EgiT sk>| 3% 37 a3n% o 23s% 22a3 23s2 23a|| PE : Half E igi.e 8H] 3% 3% 2a % 33e2%a8%a8% {2 pg Ai CC iS S2 IiBgioEdF .i 25%. 352. 252c 357s 3S2e 85%e 85o G[34% : ffi} Jog2z [I iiEE } 1ifo%iTM eg ia E>E83 |bo i iiEe = 22 ; {58 3 a8 a8 : iis 8g 8%3 | "i iM155 5zg | i iine g2E | ies aoa sg a {l3i8f Z|i PPEEEERBgLE EEgE EEuE Pol rE EgE.Ea og in i fog R}E : H 2 O 84 HEiife: if ze ome Pe gZee jefe gd i i808 & 8 E2 E: iHEE Pars Seitz Bos not contirc ~ 3 | : :2 2 g i23 2 2 4] ~ i mp yresereeemmmi------------------erins | ii2g1iog%g.s1i 530 23%2 5322% 5239 332% 32e3 23s | [ igiIa@s|P 37 2% 3e % 37 3% 23----3% | lgHi.rEElr 3% 82 32 82a 82 32 82 if E gL ion.) 3% 2% 3% 8% N 8% 3%N3% 3p g Flim} 2 EE de Eigrn $e 355 | {ia2 giz 5 8 | i =2 i i Fo i i oz Ed 25 i| ii z | sg i | i} i45 is132 tad iu1dg 8FE8RR8 E8 8EE8 ELijS8:433 BEE EEE OE ef CL, Bede | EE | % L%E2 4B LSEEBL E L Eon iEcYy PF 1 ge ie ge ge ie ge 2 lgd i {BFE EEF 8 ii; -- ee IgE a -- Tscaca ~~ : BTR 50 2.se 2s 3a 3 22 | igiggs] 37 2% 2% 23 3 23 3} UE oas eseaes 2s 2a | igiREs] 3% 3% 32 23 22 37 27 RT se 2a ae asaeas , iEieBH| 3% 33 2% 3% 23 37 37 {3 5Zi gioTn. 3as78a%e 28.2 a8s228ss Ea2a8e2 i0u T {i} ZEoiPoEle ii%g = 2gEg,0E| 1i1FF {5 |ai8z gg i TT; 1128 : zz EE | 2 i 3 g | i is H 5 &| g | 882 8 8 8 (183%% 120 : E{ BAEEIFE EEEIE| IGE it :i P Pol l E EC EEomaf noikEkal :32 iP| OF88 11| 35B5EoaEgE E,s fLggEd CSBEs80I3s fO2sE iiiiisi:g 2: }PS | ER IgE EaR i 82 52 82 1i8;4 ~i CompanySaniized. Dossnotcontain Tscacs; ~: iZ TT an im pRB i1g2izk2.1) 8g%e 83g333%g 35g | EEL oo ois g,E i (EjeEE]nE77 a ZF ERR Eb EERE E z L ig ] i13o1 g Bgwi| iiE g ii 118%;% gEgEgS IiE--i . 1i a9s3 i ~ SE PoE [5 5 28 i fg TH in 0 i g9 | : j5% 2 F5E | i i gEg 15% 3: gZ P PoEg [Hs5 5 gs {ogs; 8 8 8 134 108 mili I | EEE kK EB 4 i Po, [doaEEig ef Efof OEBof 3z 3 PiEz PE o{BrB5a5 laf d fs2s feds ge Be ye al EH : | E E05 8 13 #| ES - - ~ i CompanySanized.Doss not contain sca cay ~3 3 2 ~ i: 1 i3 3 3 ~ 8 Teeeee eeeee gE CTT 27% au 5e + 5e 2e 2m 20 on | iwiREsi ~~ ToT TTT pg ZB (Eje@RI "7 ST E ase oe oe oe ae l ae n B 3 ified T ~ iE 3 iT TTT is gy 2 |1 13 | EREEET| 2 a8%gi| j &8 | ii 5 0| i g&0| i(gLE8 | PE Rg 31333 i iYgs. aife 1[4M%E 132 Hiss3 ERg E8 R8 L8 E[5% BEER Eig Pof Pog E 2 BEE 2 id l2: oE2 iili i | EB 88% 2 32 8 2 iad | ge BNE ge ge fe fe gi tz7 TT ld Company Sanitized, oggmotcontain TSC ogy 3 =] 8 ~ 1325 43 3i 3 2z ~g FEL ET 1%1e8ul Go Bu Bu meee Bw Be Fe ----1 Be | [2gi%ghe|ToBlT 5a0n2Bw wgev a ee 2Env 2oeo 2oav | ea , (BSTl ETSa Y EeE ReE wer)if 25 iBEjEoR. TTaTn gPTe oEeM RoeM oMeeeeaeve 2i0m ET 2 iE i% gZ8E s Ei3E| H{fae] S5B8f | --ii ii $ zEmzI 2B o2%%82 ||i i iii i iz{132%8 ig2 v 5 | i ii gg& | iii i3it3z3 go {8 sos aos a 8 iff 0 Lc i : {P i BEgEE E BE EEE E E& EFE R E8B iiiY iA PEE REEEEF EEREEC PBL 980 Bef 8 Bad ia ii 8 |EEEe REgEzp E fg 2 E Be gE g gi comany Sanitizeq,Poss otcotanToc cay ~g i 2 TTTT jigZi1R0E8Eu]l GroeGro BEon GBo8E0n BGrn Beey| BjIgiEaLh,T i 5ea 7Snaoeveooev eaEnrn28 eBea || p BTjETe ETEE 080E EeE] eid ERT in ER 8 I (fie. TT TT TT EST FEE RT eT An $i i Tig sIe2gg.i1 IiFE E d 28 | i--i ~ 285 5g832%z | | :| } g 8g % | } 3 2 | air8ynF i132 i188 EiaHrd # : iIgE isd | 3 a zg P 8 8 b8 E8 E 8E8n8 e| 4 i [F EREES EEu } PFE EgE GEE oB EC i Po, bias fk :2 z PPoBgo i8 ze8 e82 5E2ElEsE5E7 fe fe Ze de Rfailfs fe ig g ! BREE EE. [3s ~8i Company san Dos to contain oc gy ~ i : F {E150oI v ovgE 8e5e R Ge Ee| HETESE E i %. | Ge Ge ae onGe 3 80 |] , (ReR: TTC 7 7 7 7AE ~ 3: 3: gd 0 PERE EEEy i: i3 32 ~ 3i 3s imicE is{2k2 zg iiEE | 1i3g3: g 6g | if | i138 EgE & 2iE 28 i i i i 1i3g8 8% : = &% | | 108 : ded 5= gz || i| si i iiiia 18% I agi| !; [iTME ag |Pe2 og3 t8op8 ro8 r8 8opi 88 ]|Do CPour l oBr Eo.r m EBE fEa oy n og i2i:f L|oBg pi e38 EoRF 5R3SEof EERE32BeEEf iiDa:l i[8 EFgee doF rog8e f2e gBOeRe iinEd, Company Santied. Doss notcontainTs cay ~3 : {E1081 2 Go0nG0 80 en | EE {20 21 gn ge igigfsi ~ Be Be 8 8 =rosn Ens || i 7 Hr pg 1(8B1jeER.|1 EE S 1B re! 8 (fieB] gig =TE.E 05iE 2 SE i GCoFCBw Gn Gen BF w Be E Gn BE w id aBo Go-- Be Go EE 132 1: i ii: 1a: {9% ~| gE HF 2 82! i jaf 2 gx! | iif fz8 15 2 85 | :i [EME4] i z | i: 32 gaz ii fi gBegk o BOBgOEgOE iiIeSfd fii i| P{fEoErRe EmoRp ox EOE;mb 1ie4d% i Co AEE a 7 Pfi OoRg OL| STEEdE E EoDg elLBfgEteR58dliians 5 {3 i ge Zed ge fe ie 228 [3d 2 : EF FE EB OE ig ~8 CompanySamitized. Doesrot cartain TSCA CBI ~3 H : ~ 3 1 g3 ZH : 3 =:z 5 ~ I|iTgmTi.e5fm.a1eE= e }gn egTe T8Tm RgTe oo ||A I igizkei7 ST FT ST , E BieEE PTETT ETS STiAyR 58 E1i2e%n. gTnPTgo ToeUTge aTe A(Be : Si & iif ii EE 2 Bf | | Z 8% | | HE & (at ' 38%! ; fig = 8gga ||| iii u118d%% go| || iigss go |fgg EEE a8 og og8 oA8 E|HB : PERE BEY :i Logi EgEcE ogEREE f fof hiN: P08 ifEE } g jaf iPgRee3g R 82 eEe .2 13d jo t= % EFFZ _ifE CompanySeniiized.Doss notcontain TSCACBI ER ~ 3 3 : ETE an osee aa ad igigeEl 2 2% #2 22 39 | e E ipiab. T}| gid {Bl | ee |eee sss sms i Z Biaefi IH g fie TFTET 0% Eglois iisH gE if 2 H5E5 ~ 23g2:a! 2sB8xl|i 3g 3gf g 43 : zi g :24 gg 00i 08 Ei: i{8og ~ 38# _-- 1if3y !| E15r% ||| igs 5 (I18aEf i ii 3 iz i migEg ii es siik3f P[pE OoERmE OEOoE mFgFOOBBornOEE EEEk iie28 FF g2i2a5t% EgVh3 E5F 08 .025 iEiEeE P| E8FgEeE EBT ef gE g<s g322E822%E1isH% dE `CompanySanitized. Doesnot contain TSCA oat ~3 i H HEE Te [RE of 2s dA ge 3 dE z iE gisE! ei : Hi 2E. iH EER 2a gs ae ae an anit 2ggE ii8imo=iB.ii---- 2% 2-- % 2-- % 33--3%i33 lIig gif = bod i in153 8gg iigE IiMH 5 28 | i--i En =3 =82%& | i| i18s% & 88 | i : i E19S% 3 g| | if :g3 5 z2g |i |Pi oe og os . gop 4Pa:d 4f igi P {R 8 EERB E E EEE R 3: gz | irE il il iggE n112 5 82 iig HiI s i i fif08f2in ikg 33 P{ og1 o{bfaReer geBgOeEgRe foeBER i|a]d] 2 : p28 FB 8 EF 8 iE Fl UNLSSA ---- 3 1 `Company Sanitized. Docs =f oomta'= TRA 081 ~3 3 --~ ~ i:2 533| :fa 325 E3i fr 8 g1e.e8:ae on se gE gHifeei 2 Ep] Tomo :2 i| diom. 3 2% iE g iis | 2EoLPgoEE i ga 2als| i i 5 32 82 if| iid Hi187 gf 28 | | id3 zg 2859ax| ii | Ee Hgi E g gd | : laf zi : :| ?i. i83. d18 i[8r5 je; Sz2g 0i 0i] o8p BMEjiOEo* EPeogogi1ul5d3 g 82 0| f| Eg BdH EaEdOFF:progOE p oE iEInS ggzag oog j|{{OBfEF E;dBEEifi.gz-Ezi8iR3dfeaAs% ag2:gi 82 fPiDifEDfM PE3 i(zEegse j RE =D2o 5 2 g 2 led FEE FCC i Company Sanitized.DoesnotcontsinTSCACBI ~3 z BT,ET 2a vo 32 Ge on 23 | : E gE T ctFRi Pzg oliigisni 2 --i oem 2 i 2 gli 1 & EH 3 i Se Se So ww Sg ia : 1 i gE2 15leBni o~ =< HI i o~ a i 2 1g 15g gE 1 5Su8 | f--!|i ~ $[E8R || 5g B2k8 || ;i TeBa | i| iE i3ne Iier . [i5i8s (13ad i: gs | {i oafizi g gz3 og 1i:i3l gg SagIe | !|0 gheesro8 n bg r0: oEB sidf Bc Bg bE kb it :g PF EEE pd pid EES 33 3 ~ PIBREFETEeE o42 ffaoyed gBe pod JE HEI Hf ------------- J} CompanySanitzed. Doesnotcontain TSCA CBI ~3 3 2 ~| i: 3 :H 3 21& EgE q 2i ~ i3 = 187550 2g 32 22 23 32 as | {gi%eE 2 RRNA 8% | Ei ! g LE F Piri &gp iidgiom1. Eo e ii i S2e% 73a 333o 2Se%o 3S%o S3g% iimz Pen gi 2 a iF ET | iE 13% s8&5: i| a8m 258% i 25 | |i| ii Ek b1ia8gs8 Fe i 8z iig }jy &| [I a| ig EeEd] <I iE oa 8 8 8 8 8 i%% g 2: | {{P8FEFEB BBBE LEuEEfRfLEE5 ERB iiefgy S| VE BF Beh eR Gog oF (if g is 28283 3% igs ERIELE F L 2 8 oie fo tual Pi R8 E{Sf E8F2 AfeE2 f RIe EBee igi j FFz FORTEOAR CompanySanitzed.Doss notcontsinTSCACEI tT ~ 3 z3 j8g1i0E8a.E7 922020am22 23sm 2oaeR 2e0s | gfe =Th : si zg igisks! } =3 (igAlEa.t lide ZZ ii 8 81 5g 5 80 59 8i 9 5 Go ia P8loBu] 8% =* 3% 32 3% 22 i gi = bo | iiot EGgE! i 41% EGgnE i| Ei:L 1 gi ist 1z age iF: 2FF8 E8 8o8p8 i{8 zd POE E EEE Ein : g 0g2. | fg pf E{8 sof 82 r Hsd EBF BoE : a 3 nHEM | : Fp Pod oi igrgieiiEenfgeify ainshc ii]n : ! RE i : FE KF ii; ~~ 5 `CompanySantzed.DossnotcontainTSCACBI ~ 33 a --~ 3 E1.ET 2s memn e an] E gamEmy TET of P g igisEdol ; 2 oEa i EBT aimee a8 @ tilt 18a dnl gon gn Ze z= HF = id } et gzl o i } 1i3n3 oS g 5Sg 8 |iP | {i%----]| : i ai{1n5g8 $EgiogF i| | i :: i1E58FdgI gx m =R i i 2if2 158 gg2a | }i ge lag zg Jz {2% g| i Pais 4 20 ibe iil 84 g 0 FPSiR EBFEg R iE E oa 18 33 ~3 = rigger pEROEE PPpdiolgyapraega faedry lBdd i {8 & F 8& {8s CompanySantzed.Deesnotcmt TSCACBI ~3 23 BfET giAE 3g"0 aS n 3e wL m za | g la piehi 2EEfieT R.iTL2.77a 3" a "7 38 i gEoiip iti ggg | I-- {f 18 -- 23 --~ E gZzE !| j: iif 5 3a 2h55 ]i z 25 ; i il EM 7 isd 3 g ii ii i E8 i iiius 3 g| : gr fi 3 i: s5 i |1 2fF i3%Ba:li i ig i5 2g:gd|i iI PEE iE $d3B33E ESeRyEd gfC(i22 {5 gEaEsfly EI df 4. 18 ype ta i4 iP f R 12E ged f 8 eBmef GEef licHh 2 [EE gid, _2 --_--e IRE CompanySanitized.DoesnotcontainTSCA CBJ ~3 3 2 Pa 3 334 Hzi g 9Z : i ~ - Ea 8.50 2aaan | (EIGER 3% ERT g: ogh ian i| 3 iE. it E zg fo lew.n3 8 ag mimi ,% :oiiE io gi i1H IEls]geE i bo--t | ] iina 111 ggg | BZi : igs iit 3 8 5 | i i 2 8gs || |i {18423 gi 152 f g5 | i ii aiiil5o% g:s [i Bg sEhEaEn oF g2 |: [EiBi C i iPFGE"ispLe Beek iinTt) fo iF PR id CompanySante. DoosnotcontainTSCA CBI ~3 23 E 181.80s aa | go i iEgisrEs! ii 3 jail iH z2 ipgii -- l--i ae 1iy gE iiminti----ii% s ig | iad ~ 3 i: 4 i 9: 2 4 ~ - EEE gE iF 82 8 |FR J iina 8 28 | i i%z g2aos 230 || i|| H1i55E3k 2" SoaorF | i| i{aidg i [i gE i io gzg | |i iirs = Poof g2 oii Ii[degFgEeMs Pi aoiPEEERe ii iE fo PF AE `CompanySanitized.Doesnotcontain TSCACBI 125134: FourWeek Inhalation Toxic Sudy in Male Rats Dupont11414 --_ FIGURES -- en tempsSeused coseotconenTscACE ~1 8 i 5 i 2 g2 [11 ;g2 h TEg 3 ag 0; i 2 :] g E 23 32 2 ~ &3 g2: i:a----al| i .. [Ji fr comm] iiis omen Suite Doss not continTac cay ~ 23 151. : cs 144 r -------- 2 | te -- 5i2 3 . g & gZz gg a8 g& Bcs zi g=s 1] ZZa Le b= Ls le ba 3 Ii ' |. - - 3 I 2 ~2 BF |. la ~- tom samoo neon TSCA acytized.DO Hi-- tt --} la 2g2 ag3a.| --~ 32 8 || I a 2 13 z= 3 I :f [lL2ee: HI::2 r5e, 5 "id = 2 ls 8 . l== 11 i5 iDdt :i : od : | [; 4 re72 fs Ff ioimnii FEY 33 a 1sCACB|I : campo stant Dot ~3 3 a, tied or 3 2 3 & : |: 5 Z 5 iE ~ :8 8 z 25 $& 4 :: - 2 a s3 % te - 2 = :2 = = 8 mo=nx s rong =. 3 ~ aposs reo TERE H2S134: FourWeck Inhalation Trichy Studyin ae Ras . Dupont11414 -- APPENDICES -- -_-- Company Sanzed. Doss otcontain TSCA = H:25134: Four-Week Inhalation Toxicity Study in Male Rats --~ DuPont 11414 --_ APPENDIX A Daily Chamber Concentrations -- --_-- Company Sanitized. Does not contain TSCA CBI 121235113344:FPoouur WWeeeekkiInnhhaallaattiioonnTTooxxiiceittyySSutuddyyiinnMMalleeRRaatss_____ --~ ee DDAAIILLYYCCHHAAMMBBEERRCCOONNCCEENNTTRRAATTIIOONNSS EXPLANATORY NOTES REVIATIONS: S.D. - standard deviation mg/m' - milligramspercubic meter n - numberofsamples DuDbuoPnoentid11l4d14. FOOTNOTES: 2 Weekly means, standard errorsofthe mean, the chamber during the specified week. ranges, and n are calculated from daily means for NOTES: Values are reported to 2 significant figures. ~ Calculations were performed prior to rounding values. --~ --_-- Company Sanhized. Does not contain TSCA CBI oi H.25134: Four-Week InhalationToricityStudyinMaleRass DuPont 11414 --_ Dally Chaser Concontrations (xa/n) posure[VeS75S5.mFarge wVemn[Sw.0.w1 mearge nam 5.T0o.r mange Tw 533 03|d0f2sa o3%s0Fs vLseIst-Ie6Es2E ee6] lldk GB1Oo LsWei-dIsdosEe|ienes O 2a0 Nm2-oI 13i0N)89 E3N 37ERE llsI lIeOlRe]la IBVL bol6I af 4HE wos Week 1*[4.8 0.38 37-55728 3.0 2-36 53 7.0 s-1005 376 |l6ee3ss 21i3d5 3d333a1-l79e55 6f61lm%a 46u% o Bm-lsdoaeel flsams 23asn aams-oidmoe0es2o o5 4|a33 328% 2I3RIIse3s e6Bh NNWO MBIIGE EelAs B3N OGoBwIS Wesk3 [53 0.62 40-65 5 2 Le 2.-2 5m as wo 3 BBn|&9 osses 3d13e8 o S32F-Ik 7s60 ea e6l l/B3me25s%2 dBm-oh3as eeellllomo s2ois soo-odaiwo6e7 L1oB |[asdn TaEe E 15II8%Ee6)le5di s8e8 BBidIs NelGi N3o waoiinwo7 weak3[5.2 0.21 47-s5[832 0s 2-30 510 2a 0-08 |e 1 psc ele nomosoluo momo B|18e od|e&7 uN1eE6 Rd 26E-Ie 7E.Ele6Ef2aM5 572053 RB22II-2NN8 G66f|1Wi1o0 7Ow.Bm4 Bs98eI-a1G2m670 -- Mosk4 [5.0 0.22 66-50 530 14 25-3 s[100 3.0 moos Company. `SeDoneshnoticonztaineTsdcAc.ay --~ Toe _ HF2-521531366:FourWWeeckIIbsaloaionTToxoisyhyStuuddyinniMaeieRRaats DuDburoowni1i1a4n14s ~ APPENDIX B Daily Chamber Environmental Conditions company Sanhied, Does notcontain Tsca cay --- HL25134: Four-Week Inhalation Toxicity Study in Male Rats -- DuPont 11414 DAILY CHAMBER ENVIRONMENTAL CONDITIONS ABBREVIATIONS: n - numberofobservations EXPLANATORY NOTES FOOTNOTES: `Weekly means, standard errorsofthe mean, ranges, and are calculated from daily means for the `chamber during the specified week. NOTES: Values are reported to 2 significant figures. Calculations were performed prior to rounding values. --_ CompanySanhized. Donotecontsain TSCACBI EE "hin bra : daa * rire ; ; J ERETEEEI saa : pens : fg. iii TE seen 3 moms 2 som 1 fe Tl ween sn 1 cane 1 2 i ~1i3 EEE EEE wr [EEE Ee IIR : RIINR : [sss : i: A. i woens smn mnand CompanySanized. Does notcontainTsca C1 ] 2IIII IIIIT easy . -- . oi im Hy pms TIHp RE r EEE I mn $I sment 2 nane 2 Tia fads a 2 E 5 Rll e add 6 msideeds dmeeanes csaanvse 5 i! Jo TT i TEReR # $883T 3 NNGES 8 ses : EI d [| =ssre z = ssi sas = n SERRE e Ha 5 3 BETT 3 28RA2 a senna : ee & : ' Bl aan nme 8 oma 3am 3 GE3I8T 8 NCTE 3IIBR CT ITLL i| i 3 ~ 2i (Company Senitized.DoesnotcontainTCAcay ~3 : A 22338 8 33887 3 3/RIZ 3 33333 8 9 22222 2 23232 2 33833 3 cases : 2| =saxs = maRax ~ ssRRs o AseRN o 2 i 23322 3 3ARER % IIIT 3 FIER 3 { iL 23585 83335 58538 8 35885 8 3 |[] svase = svass & sssns 5 savas 5 ~ i ||H ss%28 = 23333 = 3283 3 s3s%3 5 Els assez 2 asass @ 2ssss s sesss 8 [reer eww o mwmew o mewn w 1 Hmmm HER 3 rT aanmn 5 masse guess n3ngs 8 J 3 [fl : susan 2 = causa 5 : muses -2 woven wp : f rreen eneem gf omazaz gosmman g Z 2 ~2 Compan,Te tc J2H521513344::FFoouurrWWeeekkInIhnhaallaattiioonnTToovxiicsiityySSuuddyyiinnMMaalleeRRaattss___ DuDbuopwoneti1m1a4i1s4. APPENDIX C Individual Body Weights --~ --_-- `Company Sanittzed,od. poe, notcontain TSCA ogy ~% 3 =| 2 2 3 ~ | The mmam 5 i ie ASIRARAARN 2.2 Zigadrddssdsnds Z3 34 2g.i0 RREEEERIEEINESE 3 Foy g3szenEmizaddaR BL. ummmnmnm das wi qd grr gi x $85888883388888 F 383%38383838888 Com SaeedDs ot ts150 cy ~3 Z 8 2 2 ddsds i oHneas if or Re B3%y yg .7 sdanndssns 31 or ii 3 i g% is3 d i ioja aE mmR onR ia J| f er ba osERAm RAERRe REEE B60%e s1 a3Ek I ie: [Eo ------ ~3 5.2 83d: i& 3 prone $5 323 Eesgaas ~ FE, sancveases = PEE LARLLE228E = i L2 a aERnLRIE. g1 jI 1i. mnumnon :15 1ffoor m RARZRm AZAZRa IRERL i { bnEEENNEEE 4 EEEEEEEENEEE `CompanySenitized.Doesnotcontain TSCA CBI ~1 3 2. wena 3i 3 S388 2 dagds 3 2 oes 8% ssgd E ifEE --_ $5, assmoin & i312 iq if gi 3 iA LIE HR CompanySanhized. Doesnotcontain TSCA CBI 25134: FourWeek Inhalation Toricity Study in Male Rats -- Dupont 11414 APPENDIX D Individual Food Consumption -- Company"pany SanitzSanilized. Doss not contain TSCA py Tw H.25134: Four-Wesk Inhalation Toxicity Stdy in Male Rats ~~ INDIVIDUAL FOOD CONSUMPTION Duont-11414 EXPLANATORY NOTES ABBREVIATIONS: Cons. - consumption ganm/dey - gramsoffood consumed per animal per day NOTES: Since onlay partial food consumption period would have occurred at the end of the in-life period, and since that period would have included fasting prior to sacrifice, food consumption measurements were discontinued afler test day 21. ~~ -- Company Saniized. Doos notcontainTSCAcay -- Te FE LSfe ese ~~ Individual Food Consumption PSooadneCrondsa.y 7g00adnaCvodnse.y |FooojdanCeosnas.y sale, 10 mare sSShhoiuezmn a3 10s5 niiss2 2issss GSShememmises 3 mal1d ne52 8i8s7 SSGhoeatemaze z3i0ed2 noaLtd 2#3333 SSpeereitns 234530 82a0e% 2381 SSdhowiimsns 3Bw0al5 3fwe3ld 2ea05el DEFOR, -- --_ CompanySanitized.Dogsnotcontain TSCA cg) 10s H-25134: Four-Week Inhalation Toicity Study in Male Rats --~ Individual Food Consumption FCoroadanreCovrndss.y FoGoCednaaCsondnss.y |FoojoTdanCeeosnass.y sale, 1115 mgm 6GG6oh4i8es2ez6 21a4.2e3 5fix6ed 26.432 Shien me 3s in? dun 31 is 6 Gains 30 30 71 GSheienn a mio al2 niis Gouge fred nl Pa Dupont-11414. - Company Saniized. Does not contain TSCACBI we H-25134: FourWeek Inhalation Toricity Study in Male Rats --_~ Individual Food Consumption FSooadBrCToansy. |FoooCrdanCamoanssy.y lFeoeond deCoens.r vate, v 30 m/e sGGoioiooioias m333a05 p2r8e15d 2250.151 GGioeetoasas 31249s25 5#a13s 3m0e7 GGGoaoiineedasss 3lai0ss 5nas8 afBr3es7t GSGhuiuesr aBnelo nwiess 2#i13e GGfhaiaessasa aaaulse d#2i0e w3ilss --_ DuPont11414 Company Santized, `Bes not containTsca ogy 107 H-25134: Four-Week Inhalation Tosicity StudyinMale Rais Pi. Sndividual Food Consumption FSooadSnCraonas.; 0o0lTdaanyeCosiniss.y FGooTedenyCsoanes.r sale, viz 100 mg/m Sseouwsss a360e5 Bnee 2f.x4) fics 362 3855 365 eGGooiiusegeeezs a230li5s e5 2512s ae30 GGhoeiiinseess 3a21s2 7fe0d3 3i968 SGdeiairgnoe a3na1d i8ae9 wwiii --_ DuPont 11414 7, CompanySaniized. Dossnotcontain TSCA CB TTR 125134: Four-Week Inhalation Tricity dy in Male Rats ~~ Dupont11414 --_ APPENDIX E Individual Clinical Observations and Mortality Records -- - Company Sanitzed. Dpooee:s not contain Taogy ~ 1 i 3i%.320 Zaan Saan S2 an Sa en S2 e Saun Sw ap Da an Tad8ic Poyloaoaow on okon on Loi: Pod$x5 a:8 dgrE dyE B8r d8y OdEp EB DOEon88 i f3 o0d0: dBp Bdp dHdL NLp okBr fdreif fAni 82| 38 2elge sfye 2fge 2glge 2dge 2dge 2dge 2dgs 2E3s fgiazt 4543 ul4%n3a63 Tei 2l4%o9d48 Sa4f3 p43l3n4% 1H02e03 A 3 Cri ih fled in oui inn uae ih ah ah dh lake ih als dng lin 3 [RRR URERDRUBERURERE Hi | sg oz oz oz ozs ozo: o@ g ~3 Fx = = = x = x x x = CompanySanitizaq, Donote conts ain 7s,on ~ i 2 i ~ l2r 3i iid 2 z EH 2 . :1 1:pH 1B: E3:EBI: EIs : i PPoOgEgLd 2 Ba jOBEB Eh GEGhREhNE 3Z| fsfmEgy f8g b8g Lk gy 2 d33; MggaMedhpid hidid gdd B2l 0% IiRiiiR EEx TE5RxIEidRm EBixRf]ir 3 pelea el dial i [REE RERERERE i! --~ & to oo #| 2 =r CompanySaniized. Doss not conan Ts cay ~3 z3 2 i : Baex B"an Baen Dad8e aSax -fre Sax Bex Ban Ban Bas ~ 5 4553 i44414 8 PosroE EB Eno ou:on on ok : 5 8 i 5 i $T $5 C 30 5 88 i &y 83 83 23 Ey ky xy Ep Ry &y i J 1 iti ds di dhe ile fy le ih 3 Fd 4 ab 4 4: Ikki 2l 8 gy 2g 8g 8935 8g 2g 8g 8g 8g 2y 2g dg 5 IRh EREi RERnIEtRaR tal laf ata RR RR g falc ght gle BN oe ok ok ok ok ok ol 3 3828 353 Dad UsdE) Ba 3sE Ded Dad Bad Bed BW | 38 8 2 2 a 2 2 3 2 2 3 d ~ Bs os oxo: f= ox x ox por ozo3 ozo oz = x x oa ox 2 = `CompanySaniized.Doss no containTSCAcay ~3 8 ; i Tas [AM |.- Tas ~ lig Poaounow ou: 0% gg Pooh fon i: gl : 33 i Boffo 4: 3 43 i 8g 8 g3i7s 2igkxe 2Je &g Bo,38fe3r odpeye Sgheaey i Shy [ER RRIRT RE i i? 3 0} % 3 ~3 fe 5: Fe ox ox ox ; : Company Saniized. DoesnotcontainTSCA Cal ~3 $ z3i . 12 &2 S8R0R SfBaRn oRuAlRe SBRoRn SFRaRn STRoRe LTRuAmNiNs SSReNe oNonRiLRe SJBeRm oJe%s ~ |: 553% 5 0$%8: 3:8 |: PoE ody ky 53$ 535 3 + J # z 5Bs 3|: I8s8 3$s5 Is 35: Is : Body kody BB bh 308 fh h nk lh 4k HB o3 2 32da:fE8s 2.9aE4dE8s 23Rf5988Ei2Ee #aEgf3Ee S2afaefat42di%e 2B3i27e Sa4i0n%tE 2de 5vi%d 2E3706 SReEiE 2de 0aeifd 2Je oaadd 0 femmpimingndnln len In ln dn dy B3l FFaedd oBgeid wBald oBeEk a0kA uBlR aal E Ladb aNEhE Gudl oUhA 3Z3| iiifyF E0I% 3 i I 3i 3i 33 Fg g I E g g `:> >>>> > >> CompanySanitizod.Doesnotcontain TSCACBI ~~ 3 i al 2 i 3 i [ Tes Bsa Heian ~ 55 i 3 4 i Pnn on : 5 5 i Eg 8 i 8 Ey 8p Eg 3 of Loh La 31 2gis a 8h Box 215 2gagj 2Cfd E3E Tfiif bTRa:IfRITianf,E:8 iE Ta5dS 3 fea a alin i ish sd Badd BsEE) ~8s i i = CompanySantized.Doesnotcontain TSA Cit ~3 8 & PoTonio3fo3o3 ono: 3 ou on 6 : E Pof Rp d#y8 dE p Ea Eiy 8By oI&y B8y dW y idy dy5 gof3 oBdrEdm h BEEhGhUELokD i 04 J e2 d2g it& e2d d2 e 2 2de de 2 2 Bs 293% 2 i BE an 3&J FRjEHEiEBneEd gda BIR dad Red RIE Bd GdIRhBRABaNIAlDiendi ei|d d fs oz ror oro5oPo8o 3 3 ~ 3g Fx = x ox ox x = = 2 = = Coin SHBORSA ~3 2 {i 2 Ban Bas Tidnser Tan : rm 3 i4 3 ow onoy os i: P oa8 aBE m 3 8 3 eg fy EET4 : di o [RIHTEiI m R ELIL 3i Pigad iasd lualss:i ind g3 iifg ft fi g i ~~ i fF of 8 3 y= = = = < : CompanySanco Doss nfconan TSCACBI ~3 2 ~| : fio gg 1I1E1 EEIIETE TY EEOE11 ; Ez IRE 33 i i 3 33 i| F 3 dforfagrtdifiyniTdE Hmpe GU0 GR 8% gE 43 2 2 232 2 2d e3fes 2) #f ef f ] Frisian nnn a | GSjEf Sghlemeassn SgTf lZeisnsens DfgE pTaangess Sgdh geigs gCEi glnu |i 3fBH MIEN PI ROBM ED I BBD MEM MBG [EEE 8: 3 OF 8 OB il 1 . ~ 3 y= = Ee =x x ox oxox CompanySanhized.DoesnotconTtSaCAiCBnI ~~: i: ~ | ii dirF 3i3d EE [I i fom fim i3 F3 mE CUTIE E | fensr ix far d 4 f HEEdiEdH LE E2233 3 223 iar FE 3 i. oo --~ : ; : CompanySanitized.Doesnot contain TSCACB ~3 ~| & STorrrio:vorof 3i:f3f 1 ff13f1d : 2 &2 2 2 &2 & 2 2 2 & FAid EFRREi10Na hEmmEd n EEoi ihigTmRdpd mTRbfrrNIEa fR frioT os f Eig 3#2 [,RT1E8 gITeE babel Pferle ab Pfualdl HE I| OolOan HEE DfYvaalas EEE bamllofilns pDinl EEE ECE Hpial nt i ~~ fs: 5 8 ow: IEE op or o: po = x = x oa `Company Sanitized. Does not contain Tsca cay ~3 -i S111 3 g Fof: 3Ffi g 1i FLuloduahiE BaE 2 , JB 53 EEREE 1am L5IE BETE]R By BBT1R0 3&5 EEE EE if dB: ~~ fx 8 Ed oss x == i : Co Si eetco rp ~1 :z Postal Dildo itisd Jail P$iiy il 3f13d: 1 I fi 1E 1213E 11E d3 ; 33| :FF iEendfgaEpign fianny oBSndhn oiBniogus HI] silt if dk 22 ilk il il lke 23 83 Fo iPEmER cGErBaRmEiEl l lua toinmp oluard MdEaRuE 02 | jimmEREnmIImnE EEE I sg: zz i : i o ~3 fx x= zzz == . a CompanySanitized.Dossnotcontain TSCA Ci; ~i 3 $8 haul ~ iIoer oiy i Ek iz 3 d 1 Gp oii ju iB00F7 8G0nag n80a4g Ay #8 flfamsetiin iirlParegs 33| d HEEHEE ~i =| i > 5 2 == ; 2i CompanySanitized.DoesnotcontainTs cai ~% 8 [8 Liita bitin iit ina ~| 4 SPo TPRIEIE of PE 1Looinyoi iy : ff x 33% i ii iF i of & 3g0o7 bdi piiin gBeta m iiy n 2 82 25 2as faF aS 0 AREASEE ad a afafl 3 Jira ja feeln faz is fa i ji do gcigig mite na dha 2 85 8 FEF gE ES 5 55 BF ~~ I = === 2 = = = ox = = =: Company Suited.DossnotcontainTSCAcag ~3 3 a frais ~i iSyF gy i EI | i | 100d E:I 1E3a1 : PE el i FM 3444 i 3 [Ri i fr ox ~~ == : . 2 `CompanySanitized.Doesnotcontain TSCA GBI H-25134: TFoouur-WeecekkIIonlhaultaitioonnTTooxxiicictySSutdudyyininMMaalleeRaRatiss -- DuDuPPoonncti-1i1d4n1s4 APPENDIX F Individual Animal Clinical Pathology Data --~ -- -- Company Sanitized. Does not contain TSCA Caf ime SH-R251:34:TFoouurrW-WeeeekkIIwnlhaaltaitioonnTToovxiieclittyy SSttauddyyiinnMMoalleeRRaattss --~ DuDPuoPonnet-l1i14d1i4)d _-- T INDIVP IDUALAANNIIMMAALLCCLLIINNIICCAALLPPAATTHHOOLLOOGGYYDDAATTAA ~~ EXPLANATORY NOTES AGBosStoA -C asddeeecmqrueeaatsecedlotsed NHENOSOLFTD1 hnGooattrpltLeaakkceeonnnddouirteinoovnto OphFeenrofftoovfremitesadsting QBSvT D GFueR amnciesieyhotmotvalsloefficiont for testing diviCdRuoanClCNemasecadorlpoibselyocoVodanlccveteisil:oncount N5 BUTC nhhaeeammneotcolccooebriiptnuscular volume MJWCoHekC 1 hSTaeeaadnnceccloolrrppuudssiccsuutllriaabrruthhieeosmnooggtlwooibbdiitnnh concentration ARuBsSeEUD- apnlbiaatcoeelluetbrleoorcdoeutnciteclulloccyoeusscount ME Sheclute seottopniT Ts ores) ~ NAaebsws T1 iGmbmeomciivuottee ssbomecmitephil IndivMiodmIu:aSlCRodrmBaelioaeocldytcoalsltsMorphology Values: BMWLiaYe Smpoaclctirecohocryroiesesassta rERoE Balphiicnnorccymcaessia We CT mmedin WB~ 1 onowteloibosteorlvleyd bofodyfot examined; see whole blood sample condition Sastvidunt mut viccd Cott / Fiatater Horsholosy Vases: TSBO5C1 StBoomxnuilgceenbwaohsdititreoesphbillosod celts CVBCEDCI vpblaaacscuoeoollneaittieccd sclyytcooupp/ltsaamssaseipsaste GBi C1 SBmoiltaimonbdpseirpavcieediaetocsfenot exasined; see whole blood sample condition --~ _--_-- `Company Sanitized. Does not contain TSCA Cat Tire H:25134: Four-Week InhalationToxicity StinuMaldeRyats --_ -- --OINTDIDVIUDAUALLAANNIIMMAALLCCLLIINNIICCAALLPPAATTHHOOLLOOGGYYDDAATTAA EXPLANATORY NOTES (Continued) Ameviaious: (continued) Indivi(Fdiurarl CiongsDullaetaionhlieVparelmevieras:i oPrFtrD2 pSBrloNtahmreomibcTitnearebtsiniaeL thronbopastin tire IndiviTSdunEntDClintSioecrnaeesnm CSlheiempmietptaetsreyy Valves: AASSoZTn T1 ARP saSmlopereniritenoae:ceanGtsenmnoivrnasoeatpnresasfnseserteaesrease Alkaline Dhospmatas cBBuER CT1 irCSreoestnacinnpiiatnrrekorpaennte ST[ oen i 11 CShin ooltsysetaerrisdtes cai7no 1C iGLifeohwtamdidipnrotetn ~ a5k T ianormaantc phosphorous mToSETD EE pBploiarsaommtastaSuenmolyais roe blood ee he sarple for fuoride determinacion FoICnDD BDliisema lricvoerruese romblastsample for Fluoride determinacion IodivAidoLuonnt UrioGqsaltteyinsttsy v(aelduietsies color) cw 1 Slariy wosPyi 1 Ceihtiehneleosgiaurcietosrhmesatatiocf the reciprocal of the hydrogen fon concentration BnTIooLDC or 1 ubuUrrriiioonnsoeeiaibieinleoiegreivndbein mSTeE 1 SUpreicniealprocvheaisnrvations IndiviEGUdIuceaTlCUCriinueernpiiMnetiehcerwTloheisiaactobeplcibooeliolodmsoacdenicilessrattsion Vives: VNoon 1 SBoermsapn ecrevteitaese DuPon-11414 ~ _-- Company Sanitized. Does notcontain TSCA CBI Tie SHZ-251:34: FPoouurrW-WeeeekkIInnhvaalaltaitoonnTTooxxiicciltyySStuuddyyiinnMMaalelReaRtass ~~ DDuuPPoonmte.l1i14d1i4,d IINNDDIIVVIIDDUUAALLAANNIIMMAALLCCLLIINNIICCAALLPPAATTHHOOLLOOGGYYDDAATTAA EXPLANATORY NOTES (Continued) Sheenrirnedaisvoindsu,al1a1niozfalwdiactha aarree SnoXtPIrAeLpeoArteidn, thiet msaryidybordeuceoriteo:one of the following reasons or cCahhVeeraesla1vm8apslFeaAuwnlaatsutcicoilucolitdetnetmdos(acbmoepml)eobtfaoirnetd.est(iRnHg) (GS) ES7h0hessaanarimpFipaellawwSaatssedahvpoarrliioasrbuliectaobfloserampfLlooerntciSoneglslcei(cnNtsEiR)on SpCsehuredfn"ofraomnrediannodynivihcdaaullafclultahotebisoeTnrasvcaoptreidroefndowVraamlseude.rHeictohFrodre.tdheatxaseBrbileleii,nrgubSiflnesBsdIa1tLterhaunbian wcaesrtaFienpovraeleude,becaSl0c1u.lat0i.0o8nswvaesre ~~ --~ -- a -------- (Company Saniized. Donotecontsain Ts ca Ti ~i z Br3 G=2igdga5dssssieisae d29e3n9d8ireladsdy 5 SERERRSfEE SaBSfeEn: y Bo G3dSE3EEEY R3ERdedEd PEOmmMBG aban . 3 Ie IEEEEE ARERR 4 RigsRsngns sasiafizsd 2 pe RAM BHR 3 4 8% SRGAREEAEE o ANREEedE 2 gv 388%3TINE 4 3INRgRGER 2 87 sssesrsesy gp ossssssuy 23 35 : gessgigss i sEnsaiasss - Acs ~3 i [RHE SEEETcaEntaEnaDoEssnEotcoEnan,TSC 3 a ~ ; 3 7 i i z ~ 5 p 3-0 GEEEIEERE dEEmIE |i : ; 8 EEEIEEEER EEE . 3 8r 3MREEdEEY RREEERAEH 3333433433 sassanaaus Ge gzdgededdr sdzssddiny . . 8 : sddnededag i fidsaddiss fe 3 SRdFidddT : JEAN 7 ssssusssss ; sssssssass E0LI.E sEaEAEiEnEEE . oFsaIiSEHiEmDE cantedpomratconst150A ~ 3H | i 8 3i || i1 2 i ~ g3 ! i 1h D3RNNEE IIIs: LTEE* $mgI83I88E8I33En Es3gnuzg. ses Ek2 IsasEeaEsesEsa IsamEszEgsuEgs B El IE 3 IEE ERE k2o, ri entan ned I i 3286sb, 3e308 %= i ij gI azaE geaE ies g | EIa sgsm aade & = ) .Does not contain TSCA bat ~% :2 : ~ |i : 3% BInEnEEEEy sEIEEiEdd Tot ims sass giE3 EanEEn anmamaEs 2CIE 3 i snenqssssy 4339953888 : i eae : 51. 3%ainennad 1 oassnsseens z opooUTUoTg mTmTmT 2 g : Ia Inn ob cesescens | azsecerses ~~ | i SSSSUSISEI 4 S93ESISEss [oT ------ z i . 4 i Begnd Hepp j2 E HBRED2 mg oar ~~ 8 2 it | iF REEREREEEE ERE g 3 2 i 10 PU : BC sssssssess ; seeesfenes 3 3 ~ &1 333BEERENSEENEEESE cot i y [RE ~ | ir mer ppm , is | iF nEREE hmm g 7 g Perr 3 Prien a : : T 7 sseesseens sssassesss al ar g ssyiissysmsessessms: GomponySaniled,Dossnot contain TSCA ~3 3 i . 5 ~ 1 i3 y LnEogE gmeR Hi2Em88 3 i JB en =)doii t Crea 23 2 3 Ce 3 i Be z3 3: z Bo. gpggestges i 8 ~ i32 ii21f3g 33E3I333EEEsEEEEEsE Pa : Ee gg 3: dg i p 3e28ifeces 5 i JpgEaEgseaiEEass eas posse TEA Company' --~z 3g i, grpe EL --: gaan [I - 2 3 32 fof EH . E go HI Tssspsniny i pmssenanar ~prd! ap4;g oH smmnE nen g sf innn ing renLends 3 3 gontized 00% = company : 2 i 3 8 ] 2: 72 ~8 Touma cmimmn Giifdddddl EEIESEEE BERERENESE BEOBEEEENE > & z :: gaagaaaes :i g5agaagezs LRi HH EHH ? EHH HEE THEE ; seers i ~i a J TE ommmmn mans 2 |. mmpnm I=| zomen p : n i . SHRNRNNNNY ; EERE Corp San oe miTEACH i gi 2333389893 AaggeeRIIR $88 033335333333893833F] 332333R4E3I5EE%E%E% 5} smaszamzz mamwmaasus Pur s33u%nanet gazszensas ER S9dsedsisy dadsedddss De oommmen ned i 3 53 sRRRRRARs3 samsamassn : 5 2383388: Zoafisiass 8 HaEEEEEEE : [EHH Bo; onmmmn g nnmnn - g - q 1 : Hin : Hin ~3 i sEIBiEEgEl g BESEESMES ompanySaited.Dossntcontain TSCA CE! ~3i 8 2338233588 BommIEmn RAR028IRRR am 8] snzamnnsz manuasanes Ys aszlasenss ssmamsasas ta Sssfevesss SsgssyevEe _ Is sasfasass REE838INER DEMING ABEBBER i . f js #andeaases srssansass i 52 sesleazann sesmencess H E Ob . BEEEEREEE RERRONIN d| ou; iomen |: anny 3rd: mn ep 4 TINTS ~3 i 3 ~ GIIREEEEE mmammmm f.9 aseznzeans seumncaans 2 5 sEEsssiasy sfssssEsss IY yawn: manny } ~i $ G87 mE mma 4 i f 1 namasnasa osanaaans: : 3 g g i | Z i ~ 38 3 3IIIIINIT UII: ed JUIIICIN3E ok 33IAIAI JI i 83 j SessRIREr i ssseedazas - HS 1 BesIENEREE eRevEEsERs . - i 3%edBEIRE { ssssagvase Company Sanitized. Does not contain TSCA CBI ~3 2 8 sszgsssdsd gdassdises ioomEpEn nnn L 3 mpmvseent smanemsmee 2%] ggasggiisd $3safisises - P8830 i smoniesgtarsaan ssanmseuvegen:e | i PSe8d7 E mE mE m smammms 3 g 333 mile smmnnn ZEH 13 s!so moms 3 :2 oTt,y sssdkeseses : smmsonmnn: 3| 5B3F 32358.3833 } 53ssEesioy Fi 2 i 3 828 ER 7 > ansduseens i 5 snanssnsss = 2 2 Cor PAYSanili)zed.Dosnot contain Tc ogy ~i i | 3 2 Bl anassossn gsansasadms 3 2 3 fF, HEEREEEEEE HEEEEEEEME 5 z : 81 anaes [Ri 3 : To iF. pREREEEEEE - RERERRNREY | 3 s 75 5 spzoszzoss 8 s3zssmoss: (Company Sanitizad. Dossnctcontain TSCA cay 1 : 3i 2 #1 canananan ossninioa rmaamn <I; 2mmm: pmenn HI GHERRERREE BERRRRRRND Company Sanitized. Doos not contain TSCA Cay P ; oon mem osm amu Pg anus osu jum amos ) --_ 3 $ g s% 38333 209ST o3Isey fim ' o| Egpd FmUeSmeeR IszRaAaEn ewaapmnren epsezuzxe : 8% sssas ames geen sees db, REE EE, BIE DM <J @ zme : om 7 men b. n 3Io i HE HE 7 ET Co Sent eetry 5 a gd INIRIT BNRHN: Polina CO 1111111 1 8 eretezanct aan HH g exefafons ~ | IF HEE dIpEEEEE : 8 ) gf ff EERE mene i g7 J3fiazeNe: adausdvse 1 : SEH HIE % ul 33gas5ae8 sonsssszes . Company Saniized. DoesnotcontainTSCA cay J 5 8d 3333333337 nJ!HIBW TOBIN nn SO [HHL 8 OPERT TRH ~ | iE THE i Pr msm snensaam 4 89 IITINeIIroaRIdesisas Doe num mn 3 55 ssspssaess { 5E385gEEaE : CEP Sz Dosntcontin 5 --~z :3 : Po i 2 0 g i95 g8e 73 3i g3 t88 iaFLdn3 sergE.a23 E ioe fesRasssss I F , sEsdfeRsad Esagasasii 3 3 Br 3 NISEIEINE . p SIIEEIE 8 #33 % zazasssass : sssssanams ~~ i B3BEBEENNE J sizes Company Sanitized.DoesnotcontainTSCA CBI ~3 3 : 3 --_ i = ! 3 2 3 1 3 4 2 i ~~ g3 eo ti : 53 : cefzasasis % BEEEEEREEE] fr. p3s3iiisl ZmRisiiiis : osnsesnses 213: osEiEEREEgE g # sEESEESE Company Sanitzed. Dossnotcontain TSCACBI ~3 8 3 ~3 i 5i 231 bor bE : i g :: Bel: Enaad I pS jsamE e 6 ana i ~a3 g sgass fHgHEE H uspmas f EsaEis sae Sanz. Cos econ rc 3 1 | 2 HE zl I 23| ~ 8: : fred EeELRRREE ie IRE SEEREREEEE dunn ssnstfunn El 8,2 HEEEeEEER i sefuEEREE 0 mm spe fo.i BsaEgEsjeEEEigye -;| segpaasfgsEsRiEs ii Ei 3R33I525T32H88 ERE H 3335E g0aH ga8 Com | Sanit Doe oto 13 gg 3 2 { 4 thenzenssr ssedsganne ' 3 g f it Jrsmenr i Hb mmermemssr esprenzned 3 $ 5 |. Bedisecd sebieBiing H 2 . : : Eisdfefeed esBiefRREE dF menses sarnanpise &3| ax 8 szzzsszass 8 prasssessy CompanySatied. Bos not consi sonoy 121525113364:;FFoouurrWWeeeekkIInnhhaallaattiioonnTToxoirciitcy SSttuddyyiinnMaalleRRaatss --~ pDuuppoonnte1i1i4a1n4e APPENDIX G Individual Animal Blood Fluorine --_ ee ------Teeee`CompanyeStaenirized. Doses neotcrontNain TSCA Cat 221321513344::FFoouurrWWeeeekk IinnhhaallaattiioonnTTooxxiicciittyySStuuddyyiinnMMaalleeRRaattss _______ -- DuDPuPoonnetl-1i1d4i144, --A-- NIMA[IIL NNDDIIB VVIIDDUUL AALLAO NIMO AL BD LOOF D FL LUORU INEOR ~~ I~NE FOOTNOTES: EXPLANATORY NOTES a Insufficient sample size for accurate analysis. b Sample not analyzed. ~ -- Tm Company Saniized.Docs notcontainTSCACBI < z i owmnooamn osm oom i SpEpEt E amarEgE man aneemdo aanenws ~ if 3 2: EE aaa 8 4 H in wm aE 5 1: or : if: o :3i if 3 E: sian ~ OEEEEE BERET J BEIGEchkibkaiocononsTSnOAeCtH! H-25134: Four-Week Inhalation Toxicity Study in Male Rats ~~ Dupont11414 APPENDIX H Individual Animal Final Body and Organ Weights ~ Company Saniized. Doesnotcontain TSCACBI TT ~ : | zlsesagsasen 82) | Blasaeiasaes ag) P Niowmmn Sonnwn i ighiseddusnans a2) [gfisicdssaued 211 } 3} e---- i =i igi bBleezasasspesaa2gi dfn 3 np 1 Mmmm | ove prompt cers me| fBl go7inmapaeasmiaen aa5m De 1i%713333308388 8) imam 3 igNRan SE apEmE a if 3| .1j3----i{zSszRsZaRaREmIERsAR2S3oi niif (REARAEIEgREREAEAE RBLRRlI 4 ~ Gompany Seniized. DoasnotcontinTSCACE! ~i i pop gli Tj ofo T mmIiSELghB umImT f 3igf EERE 2 gl giaggopmanan za! nian ! gigsasmeensz nal gi Ha Seb mn al Id mIEEE Eee no g | pigggasnuany 33) oi pisdsEssEnes gs! i ppEEEEESER RR pmEEEEERRl GDL i HAs Heer7. I CmiEmEmE apm dl Com Sen Does otc 1304 ~i | idnsiidased a1) | 3ieddaneases Aoi 5 i |nsddddadds ad i Jirmrcdnnnna ad $3 Demand ||piigssozoaceansraeyEBoaOgm.i as || p|iaBgEaEsEESsEuSmEaEsE FaE3. fi= ul Bpionssgisazasss iagifi foizesssssansgms sz) aq = Ri HE 3 I igBirraseer 2x 0 irassreaes Elo 3 Li% igazssssase | Lig isessssmmsn Ll ) `CompanySanitized.DoosnotcontainTSCACBI ~3 2 fej feet || fi5tiiSe3SnRnSnIiRnZeAdN 32731) || Hgii5d2s3iBaEsAaSn%eend 5a%d) [EEE gpla ARIES iBREIBNE232 BR2! Emmh gp: BEMGREIE 19832822882 REBA E Dolm mam n 5 i Jirvdndnnass sdf j im am le i Jisnnndandd ssf dl og 13832230858 881 | ziON8BLEES92T 83 |8g3fppEEEEEREERIBEECOC pgSEHEEERNAEEEE0R 3 2 i "iosmecazgas ani #1,"isgs-gesage gn fF lg pee 3 = | ~~ 8 inadgiiaadd <3 R Jiddddasadid a i pm ra I1d hpi TK - . 13 [3338833338 ..i .i igBEggegger i = giz |sEseEseses i ff HEE LEH 5 CompanySanitized.DoesrotcontainTSCA CBI ~ ~ | 7} EinEeEE gallema& 2 Poo | Spiig zElazEaas Esal 4EdiE saceeEa EI lis Bl Higin ui d mn Fan Z| yi EIEEEE 3 i iasss od 1 mms mma | CosBaISEiEEEg1iEiEFiaG8Ee03 na3, 4 nr [SS---- ~% BiB I fp BEEEE BE: ft Sammon mma }oighinaad an fide } | gGid me wl L GRm EE 33| g2h i inaazn gEoml B1R 3 ine anas 5ga i BOLEEE EB IR HN I3 e Hid icn sewerr CipM pivE ennsS mi? A iim SYise, |G 3 `Company Sanitized.Does notcontain TSCA CE | oe ~ 3 |Digaianseeag eari | oBgiEsnEes 3g EEE GEER 3 i pgligzaesasyn asgaii || fpilseamfeenss aaad j EERE pees i | gismses gzi | pisses ap ~ P o| iBidddsss sdi] |igsFi3d0s8d3d8d 483} 3 FRE EE % qo L ERE 1 Sma Tae ] jelEL nEEE 2! ~3 wisi] Bi ieeee--! 3 HERCULES LLLCH CompanySantized.Doesntcontin TSAO ~3: 2 am Preeraroti aPrvwegeng CRE REE BERR pER jE Fi _iBZQ48 ER) Ee | iERESE 88 qa y Ponm sa 85go%TpFglfa iFiizssdEeEssEzs naEsil) g| ii _isszsg sai i5 Bgli gogiirnegmznass 5am}l ams fRmEmL fgflhan3ia3ga3zn%a:s iaanps i imesss gel Jo}l oggiieniaemnass oa ) 1 Beinn iTinma J CipEE HE gE R I ~g3 f R.1gii immae sEgkdpi g eLig jEesE eEsz Eii O . anid Dossnotcontain TSCACE! HL25134: Four-Week Inhalation Toxichy Study in Male Rais --~ Dupont11414 APPENDIX I Individual Animal Pathology Data Company Saniized. Doss rt contin TSCAcal Te H-25134:Four Wek Inhalation Toxicity StuinMdalye Rats --_ INDIVIDUAL ANIMAL PATHOLOGY DATA DuPont-11414) KEY TO APPENDIX HSFeOivGseItrEoiLptCayLt.sholsTouhgceyh cGashiasntfgroeciasbly,atriemounldte(issfcxortcieabnlte,dofa4ictctfoiurssdseiu,neguintriovloaittvheeersiaerlnc,s)orbipilhaotlieonrgdaiilcc,atcehadcae,r.acwtheeArr,esedSvpiepsrEtiortpiyEbiusstetoierorsn.sbnyLdf Sopropriace, 1s alo asaigned as follows: KOUNAL The amount of change present barely exceeds that which 1s considered to be within win: VOOERATE: seven. RInogbeneiralG,oeschenotlepsrioodnucies eaansyilfyuncitdieonntailfieidrpabiurteeonftlinited severicy. The lesion TChEe RleesioTneatleeporrostonregnatn bduvtatutnhcetrieonis16sipgonsisfiibciaen.t potential for increased severity. TThReidnetgerneiecyofofchaenxgteentiateoietxhpeerctassciogmnpilfeitceantastciosnssuiedoerredorgpaonssSiybslreunocxtigorneat enough GSFerinanidaaenns"mrieanfliezoranlSeetSbhhereionugSgohithmseheovlelorenesise:repscrehevasetersnectteaprnridosgtsiraoevnsesrisovfeieLsieisniovononslsu,beesieSnnhgte/ystaehiveesremiecsiytndaSielovosentrgee.athecWlohrnitlrieenlutaehteiwvieth ~ Eolas significance. GBroess caharesevatsions Listing multiple masses for a tissue are distinguished with letters (Le. A, -~ Company Sanitized. Does not contain'TSCACBI - ae H-25134: Four-WeekInhalation ToxicityStudyin MaleRats --_ Individual Animal Patholosy Sate Grow: I concentracions 0 m/s Sex: wales Animal Ref | Microscopic & Macroscopic Findings seiniz TiEexirpimoeimdnaarloenGSbaracoyrwi:fi+c3e5fact TR 1a Shed oF exon necropey Gross patholony Yo NSLaOIcRVrTEoARs.,caGKpRIAcDINNEA,YbSn,oSrPmILaNUNlAGiLSt,yCOROWDEb,AsReTSr,TvOeMdSAKCEHL,ETDAULODMEUNSOCMLE,,JSEPSLUENRHN,. ARTOUDDEER,,,SPACALNILCVARAESRAY,S,GLSACCNIBDNSCF,L,CANCNEODRLIVOBERG,,LARPRBITCLUHYIMWT,PAHRNYEROGSDBLEUA,TDE,RTIICNSLY.kPH RTINVRROLDLGLAANRD,, PBRYAEN(TSH)YRWOILTDHGOLAPNTDISC,NETRRVAEC,HEAS,KINS,SOPPHAAOCGUPSA,TE. FRMUR/KNEE JOINT, STERWMN, NOSE ' " Histopathology, INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, minimal. ssn. No MKBiRCcAIrIRoNEs,vceo,SpPeILNUANAGbLSm,CoOrRmRDaE,AiRiTSc,TyOMOSAbKCsEHeL,rEvTeADdLUODMEUVSUCNL,E,JASJPULNEUSMN,, AIOLRTEA., rm TSSACANILCAIRTVEIAACRSY"NGERLCVAENH,DS,,PINCTOAUuNIODTNATRBYUNLAGaLRcANhLDY,,SoHMTHeYNORsDOEtZ,)rACeLDARULEDN.AhL GLSAND0S.8, USERXXTER(iNSNT)RAYVWRIOBTLRAHDDDGOELPRAL,NIDCST,NEESRTTVERESA,,CHEE`ASPK,ILXD,EISOPOWRRIOAOSGETUSAS,Y,S,FEPMSHOEARWR/IIMNARANEL/EVLEJASORIDECV,TL,ES, TER, BONE NARROR, NOSE. oes or XIE: DuPont-11414. --_ Company Sanhized. Does not contain TSCA CBI Ties H-25134: Four-Week Inhalation Toxicity Study in Male Rats --_ Sadividual anisad sushotony ace Grow x concemseations 0 soset sexs ales Said at Wiereris & Mecroseapie Findings Gea TSJ EermiEnE alA LsaL crificBeF rom cron rons athlon + io sSaP crEoscopSe isanAtmoSr resbaitnigcyce omopbeserSvreoduGh, Diovan Sos, SEB SENN une, TRA LE RRR, SH. FRF RRSRA TCNseotshseSkaRhtGsRt,DytoStisoke,es TAGs Teves, Ecos, Ebioronaots [---- wovenSirunenrion, sicoT/CROV, SOCK, minim ~ . CWAiRhDIoOnWnYiOPoAnT,HYs,omcinoimmal/.cimonic, sinioat. 35 WiEcrRoscopLisErm,orDaalLity obTseOrvRe,d sam, orn, wc, SCCEEEERTsRRSY,:SAThRRsSiTkbResoR,tvTeiAT:CsHEoSRRE:rR,EB, FOTIToGTaSsE,,tsNoSonREmAeENaLaSLaisas,. BfErEReTTeHGEerEeSthieCnInSMISSEhSi. PSAeREvESLTooLlEeS.. SaRnNdRr. DuPont-11414 4. Does not contain TscAcEl Company' - -- BCR H-25134: Four-WeekInhalation ToxicityStudy inMaleRats --_ Individual anisal Pathology Data Grow: 1 Comencration: 0 mg/d | sex: ales Anisal Rat Microscopic i Macroscopic Findings Snnie elErxipmeoimndoarleonGsbraacoyruipf:ic3eS5ac1 ATR Las ined off trom nocropey Gross ratoloay Ho NALaOicRioTgsARc.,opBKiRIcNDIUNAY,bSo,SrPeLIUaRNAlGLSi,yCOROHDEb,AsNeErS,vTOeMdSAKCEH: L,ETDALUOMDUESNCYL,E,JSEPSLUERRI,. RSOUDBEI.R, SFARLATCVRAERAYS,GLCANCDUSM,,WACONLOOIVB,VLRAERCTLUYNM,PHNNEOSDBET,ERTIHCUSL,WP S`TRPEVRIRANORALTLDX/VGLLEAASRNIYDCR,L,ESP,SAVRUEA(RTEIR)NYARWROIYTDHBGLLAOADPNDFDELSRC,, NETTRREVASECT,KEESR,S,KIENEP,GIODPIPADRAWOGNSUITSOA,ETSE.. FER/RUES JOINT, STERN, No%E Histopathology ATROPHY, FOCAL, minimal No MJiLocERVrTEohRs,,copSKiAIAeNTEKA,VmSo,SrPmLIaUNlNAiGLSc,yCOROHDEb,AsNeErS,vPOeMdSAKCEHL,ETDALUOMDUESNCML,E,JESSPLLREGENN,, `TSGNEULANIRVD,SA,RYCH|OSGOCLNEA,ANRDISCC,OLNoEWNRAV,IED,IRSEUPCLITATRU,ITLAMIRENPYSREGNLRTAOENDRDEI,,C TLTHAYYIRLNOSI,RDODAGSLD,ARNEDN:AL ~ ECSRAXIRESNA)TRHYARGEBETADRDEGOLPRAR,NIDCST,EKESRTTVERESA,,CKESERRP,ILD,SIEDOPWRPIOADSGETDSAS,T,E,FFEMSUEOMRI/NKNANLELSAVROEYSIEINECE,L,ES, STERN, BONE MARROR, ROSE. DuPont-11414 rscACEl --_ Company aniized.x D008 194 ae Ti H25134; Four-Week Inhalation Toxchy Sdy inMaleRats -- Intiviaual Anica Pachoiony ata Group: t comemtrasions 0 g/m sexs sates pen Hicroreopie & vacromcanic Finsinor Geass Tm ETepEromRinnai s scercroiticeb5iertrem mecropey rons pacholon+y 40 vaRcrRoscopRtes npiemocTeoanleisc,y baa,sedsrk wscus, sven free Tg oha agesBe NRoomtahd EGNE: CsHeamATRGIeDRS,ASH, TeRACECSoSnaomcs Te Ea oo, Teves, Eaioronae asasopachotony Dupont1414 HcTentNsPLA GIATION, SUBACUTE/CHRONIC, NFOCAL, minimal exsacinass Sous : -- Fiar t. ELBo AWSLS,l Shue, o aon, sav an, spol eSANiDIiuSLEnRLGEi] CToibaen,,Sva:osoAGDKiEaRA,L CSeLAAcDhEc,h. SBCoImAsPcs. Co Es ACh os, Tesvks, ERioronASE. SRerRaiD Sos cacel ~~ Company. LL Hun 125134: Four-Week Inhalation Toxicity Study in Male Rats Dupont 11414 ~~ Individual Anise sachology Daca Grow: 1 concentration: 0 mg/at sex: Hales Raina Ra iczorcopie 4 Wacroseopte Fintings Gains efEeiipionmrear]e scapheoriptd:igsSact ET ecm secropey Gross sachotoay No MSaScovrnaoens,:copBRtiamsnuaAivbem,dooriTmiaoolnsiet,CyonODsbE,sAeErS,vetdSoX:LwETASLosssca,SzEmR,, bSienSshLSTaARsY,CSLesteWoNNRDEIS,SLAFR IDGRMCODLEA,D,SRE, TEIIMACRiNALCVRhSimci,is,BUCSASS)ARRYETABiaOoPoEtSs,NETRESGG,ES.SKISNH:OIPDRWOISTSAETSE,. Histopachology Evanson, someuTe/cHRaNIC, Tock, minimal. VEPARORATRY, CHRGNIE PROGRSSSIVE, minical. 0 MCinocnazno,sscosphutacsnkpaab,noSrSEsoaoLthEiEtNSyN,oWbSsSeeirEpv,Sed,shusTmLy.E,outPaR, CmTa,nyCosonp,r a. 0VSE1ART0Eh0,uLTPaoInTCUKiInT,AeRYSwCRoromaamb:e,RiScTRIESNe,OnACHCoLKoIkEN..RSSSALXLIAEVNSAPR,HYRSGSCLEHAISGN,EDS, TREVEaRA)eChBrAESDoOToFIPEASLGiLcST.eHERPRE:A,RSSHKIIADNRIOIFMEAIG,SEoSa,re,FEsRmAMuEEveTsoitceu:ss, Shinn, So an, 055 Company anid. Donotscontsain TSCA - cal ~ Te H:25134:Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414. --~ Individual Animal Patholosy bata Group: 1 Concentrations 0 mg/m Sex: ales Anica ret icroscopic & Macroscopic Findings TT Geant TEKeixrlpmloiesnduarleonGsrSaoacuyrpi:fic3eS5act I Aninal is signed off from necropsy Gross patholony + Ho MaFLcOErNEoTRs,copKBiIRDcANINEA,YmEo,SrPsILNaEAlLt,yCORoHDbE,sNerS,vTeOMdSAKCEHL,ETASLUDWDSECNL.E,SESIPULNsAE,, ARIOLRDEEEU,MA,LSAPGLALINACVNRADERSAY,S,GSLCCABISCASOT,NI,CMANCEVORLDVOIENB,,ULARPBRICTHUAUINMT,AVRYENSOGEDLNEAP,NEDR:TIHCORLS.PH PSTUERUAUIRRNOYALILD/LVGLEIASRNIDCR.L,ES,PEAVRUEA(RT5IH)NYAREROYLPDHBGLLAOADPNDRDEISRC,, NTTEAREAVSCETH,EESR,S,KIENEP,SIODPpIEAOAOWGSIUTDSAEC.SE., PRAIRIES JOT, STERN, OBE Hiseopachotogy + IEPLASDIION, SURACUTE/CHRGHSC, FOCAL, sinizei NEPHROPATHY, CHRONIC PROGRESSIVE, minieal. 'ARROPKY, FOCAL. minimal, --_ No MiC"LcOURrNDoG,sS,coSpTHiOENcAARCTAH.m,oSrK"sEDaLUlDElETcNAUyLN,OMUbSsJCEeLJrEUv,NeCdRS,P:LELENE,NAORCTBA,M.BRCAIONL,ON,SPINAL PpEICTiUMI,TASRoYNDS.SGLEANTNTHDE,IRISCT,HYLARuDONIREDHENGANLOLAONEGD,L,ANSDAPSLA,IAVFASRHCYII.RNGGCLLEADCNDGNSLE,ARNVDEWS,A.NBIIULAR USTYRREAI(CNSKA)ERRY,irBrLSAaGDOOPORAPRAT,GIUCST,HEESPRTRVIAESR,,YRESNKPOINLD,AIOKWFIRINOD:SETSA,TE,FSEEARZNNALSVJESoImC,LES STERN, BONE MARROR, ROSE --~ `CompanySanitized.Doesnotcontain TSCA CBI Time H-25134: Four-Week Inhalation ToxicityStudy in Male Rats --_ Individual Aninal Pathology Date Grow: Comcentration: 0 mg/m Sex: Wales Animal Ro Wicroscopic & Macroscopic Findings acini eTErximpeiondsaelsonGsBraacoyruipf:ic3eS5 ac Rnioal ie signed off from necropsy | Gross patholo + `DIGCOLORKTION, YELLOW, RAISED, RIGHT, SHB OIA.. No M"aLcirvoans,copKIiDcNEAYmSo,rsLaNlCiSt,y OMbEsReEr,vedSKELETAL WUSCLE, SPLEEN. NIOLDEEU,M, `SPAALNICVRAERAYS,GLACNEDCSU,N, ANCDOLIOBNU,LARR.ECTLUYMM,PHMERSODEEN,TETRHIPCHLLSI.MP PSTAHERYWRRIYONIADL LVGELRSAINTCD,L,EPSA,ERYNEUT(RHSIY)NRAORWIYIDTHBLGAOLDPADTNEDIRSC,,NETTRERVSAETC,EHSE,AS,KINE,SOPPHRAOGSUTSA.TE, PERR/KEE JOINT, STERN, WOOF Wistopatholony + Er ErTorSormEIRDuIASOCELE, moderate. : No Microscopic Abmoreality Observed : BSPRAAANLICINRV,EAARSYS,PGILNCAABNLDCSC,,ORDNC,AOLNODSRIT,OSMUALRCAEHRC,HLND,EUONDMEENSNUOENDN,EC,EJREITJCHUNULGYSMM,,PHAIDLNREOUOENEN,,AL GLADS, SCINTEC, NERVE, PITOIFARY GLAND, TROIS GLAND: ECVREI(NSA)RYWIBTLHASOEPRT,ICTNEESRTVEES,, SFKEIWNI,R/KPNREOESTAGTOET,T,SBESIPNEARLM,VESIBCOLNEES, DuPont-11414 Company Sanitized. Does not containTSCACBI --_ TT H-25134:Four:Week Inhalation Toxicity StiunMdalye Rats --_ Individual Anima Pacholosy Data Grow: I concentration: 0am Sex: wales nisl Ret Hicroscopic Macroscopic Findings fer EETexlrplmioensdaelenGsrsaoceurpif3+iceSi Raioal 1a signed of trom necropsy. Gross patholony + No MAaLOciRrTgoAs.!copBKRIiADcINNEA,YbSm,SoPrILeUNaNAlGLiSt,CyORMODEb,AsReErS,vTeOMdSAKCEHL,ETADLUODMEiNsGcNL,e,JESIrUeNeMy., AOTDDLERE,E,LSDAGALLRIACVNRADERSAY,S,GLSACCNBIDCNSOT,NI,CMRACENORLOVOTENB,,ULPRAIRETCULOIYMTM,PAHRMYENSGOEDLNEAP,DEA,TLCH.ISL.PH STPHHEIARRRIOALLD LVGELASARINYCDKL,E,S,PERYSUEARSRI)HNYARRWOYITTDHBLGOLAATDNEIDRCS,,NTTERRoVAsEC,HhE,RS,KIENEF.SE0DPIFIORAWOGNSUITSDA.ETSE,. PRR/KiSE JOIN, STERN, NOSE Histopathology + xeoweNrHEsUPOARROON2EMPTHIRYG,S1SC,HROCNNIILCATPERROAGLR,ESSmIiVnEi,maminimal No MiSLcIPVrIEoNRs,KcopCLOiiRenDs.A,bSnToWOErRAmANaTGl,Hi,tSyKDEOUOLbDsEEeTNrAUvLMe,WdUSJCELSEU,RANS,PLETELN.E,MOTRAON,CRESAWSA.IN, -- S`CCBCLCIAUNDNRE,L,CCNWOAELNRODV,IES,URLEFACIRTT.UUMLL,TiANWREEYHGEGNLONADTNEED,R,LCTTAICGTMRSG,eEDKAoGDoLAkNE,D,ASAGLLAANRDSY, SCEERYXTIGEENNSRAT)RNHYV,WRIOBBTLLAOHDDNDGOEELPRAMT,NAIDRCSRT,ONEWES,RTTVERESAN,,COHSEESSAKP,IIND,IBOSWOSNPRIKOOASRGTSDA,SS,E,FPESHVOAHRROGIANILE/SLVASEoSRrIKvC,Ti:ss, DuPont-11414) -- -_-- `Company Sanitized- Doesnotcontain TSCACBI - BEN H:25134: Four-Week Inhalation Toxicity StinuMaldeRayts ~ Individual anizal Pathology data Group: 1 Concentration: 0 me/m Sex: ales Raina at Nicroscopie & Macroscopic Tindings Gina TEKeixrTpmToiesnduarleonGSaSrcaorywif:i+ c3eA5ct - nial io 8igned off fron neczopey Gross satoloay No HOaLcINVrTEoARs,.copBKRiINDcINKEA,YbSn,SorPmILUaNNlAGiLSt,yCORWODEb,AsNeESr,vTeOdSKWE:,LETDALUOMDUESNCML,E, JSBPCLIENERNY, NRSOOLDEER,HB,ALSPAGALLNIACVNRADERSAY,S,GLSACCNBIDCASOT,MI,CMNCAEONRLDVOIENB,,ULAPRREECTTOLUIYMTM,APRHYNENOGSDLEEAN,NRDE:ADLHVCAULSi.vi PTSEEHARRIRNYAOL LVGAELRSAIIDNC,KL,ESP,BAYAEUN(RT5IH)NYARROWYLIDTHBGLOLAADTNDIDECSR,,NTETRERVSAETC,EHSE,AS,KIENEP,SEODHPIOHDSAWTIUAOSGE,ES.. PRGR/HNES JOINT, STERRN, NOSE Histopathology + LovLAFLASOTION, SUBACOTE/CHRGNIC, FOCAL, minisal No MiBIcROArIoNNsS,co,p`SiPcOINNAASbLn,oCrORmRDaE.AlRiStS,yTOMSoAbKCsEHeL,rEvTeDRdULODW:EURSICNL,E,JSEPLNENEN,, ATGLREA,. ~~ LSEKAARLICIDRVSEA,ARSY,SGCLICARNNCTDOISNC,, NEMCROAVLNEOD,NI,SUPLRIATERUCITLE,YAVRPYHWGESRLOEADNDET,.SATTLHEHYARLIOSiI,DkGALDHARONEEDV,.AL CTEERXAISC(NSHA)ERRY,WBiL"rSASSOOEPPRHTA,IGCDST,NEESRTVEFESK,,ARIESLKPRII/NDL,IAORIWPYIREOO,SRTSA.TE,FSEEMRINNASL VESSOINCNEL:ES, EReNTRIROLD GLANDS DuPont-11414. CompanySanitized.Doesnotcontain TSCACBI --_ 1% LH2:2351534:: FFoouurrW-WeeeekkIInnhhaallaattiioonnTTooxxiicciltyySSttuuddyyiinnMMaalleeRRaattss ______ ~ DuDPuoPmoenitl1d1l41d4 Individual Anisal Pacholosy Data Grow: IT Comcemcration: 0 som Sex: vales nina Ret Microscopic Macroscopic Findings . " Sain EKeixrlpaloiesnduarleonGsbaracoyruif +ic3eA5 ct TT Rninal Ls signed of trom nacropey Gross racotoay No MAaLOcIRVrTEoARs,,copKSiIRDAcULENAY,bSm,`orSLmPUaINlGNiSt,CyORMODEb,AsReESr,vPeOdSNKAE:GLHETDALUOMSUSECNLR2,JESSLUENDA,L AOSDOLER,EEALSAPGLNNILCVARAESRNY,S,GLSACCNIEDNSCT,I,CMRCAEONRLDVOIERB,,ULAPABRICTRLUUIYNTM,APRHYMENOGSSLHEAV,DF,ETNIHGISL,ib STERBAIERRNOALLDLVGALERASYNINDCK,L,RS.PEAVSUEA(RTSIR)NYARHROEYTPDABGLLAOADPNDTDEISRC,, NTETRSRVSAEnC.iHsE,AS:KIENPE.DSIOPDPHWRAOMGSIUTDASET,SE,. FBAR/KugS JOINT, STERN, F082 Histopacholegy + TF reason, svancore/cinonze, roca, sinisal No MBKiRIcADrINoNEs,YcSo,pSiPcILNNAAGLmo,CrOmRNaDEl,AiRScS,yTOMOSAbKCsEHeL,rSvTeADdLUODWEUNSUCNL,E,JSSPILNEME,N, MTRLSEA., --_ GSPELNAAALNRNCLNDRUTSEAI,NRTSYR,OSGLCLDICARANGCTDOLISNAC,,NDNSEMC,ROAVLDEOTI,NRS,AUCPLHRXEAESRRCU,TTOILNAYB,RSHOYEPNNRGEALNSGAOEUNSNSDEI,.,GhTILPcYUSRRLO,ZiDkCCAoDALRbAREDsIN:,A,L SOERYTIEeNSRA)RiY,WIBBTLAOHDNDOESPRTW,AIRCRTOENRSE,TREVSEN,,OSESEKIED.IDWPIROOSRTSA.TE,FESMEUVNIIWNAELRVESOSNINCEL:ES ~~ -_-- `Company Sanilized. Does notcontainTSCA CBI ie H25134;FourWeck Inhalation Tost StiunMdayl Rats --_ Sndividunt ania Pachotony uta Grom x concentrations 0 sgt sex tates Dupont 11414 Animal Ref Microscopic & Macroscopic Findings 664822 JS TeErnGinah lFelSA acrificren I ---- svnts) wim ove yams 0 sSa aBcorrEo,scoPSRpiRoRAoNmatsrseeaosiicn,cyoBonSbsEeursvredSoSea,ntaiS,oewSenecaieeee,neisemATei,e fRSf EaEodSrr ESAaaR,e Se Suee,anRTce eoR,APTrroLrReEARyhaSnes,niFn: =SEA Reeves, Erbin ron ne So Sve [r-- 0 MiS croscopR ic smorsaiicy cbeerved cours JEFEERRLFol--A--SP -- PS Gross rachel + so soaBecrrnERos,copRBlisntsnnmosrmeTahaotnniscn,yCoEonCbgasoenSrnvoeSduRaektimonS,, aEwSmceee,EASLseeiRnzei,n A SALA Sian SERIAL LEY Tape Ss CN Reia nerys Sonees teachesT. oEocs,r TE soa hoe : [r---- 0 Microscopic simorsalicy observed CompanySani 26%. D003 netconTtsaingy ~~ TC H-25134:Four-Week Inhalation Toxicity Study in Male Rats --_ Individual Anisal Patholosy Daa Grow: I Comcentration: 0 mam Sex: Males nisl Rat Hicroscopic i Macroscopic Findings Goin AiTertciaeaidlnalo{n2'ssDaiacgyrniefdic5eo6tt from necropsy xoss athotony + Ho NRLaOIcNVzTEoARs,.copEBiRIcADINNEA,YuSm,oSrPmILaUNNlAGlLSe,yCORWODbE,sAeRSr,vPeMSdAKEC:LHETDALUOYDUESNCNL,E,JESSPULNEAEYN,, ARTOOURERE,NA,AL`SPKGALLNIACVNRADERSAY,S,GLSACCNIBDNSNT,I,CNNCAENORDLVIOEB,,ULAPAREICTRULUINNT,AWRYWNEOGSDLBSAN,NEDS:HRIACIwGb SPTERAUUAIRRNOALLD CGVLAEASRNIIDCN,L,ES,PEAYSEUA(RTSIR)NYARWROIYTTDHBGLLAOADPNDTDEISRC,,NTTEReRVsAEtC,iHsE,AS,KIENPE.LSOOIPPOIRWAONGSIUTDASGI,SE,, PRAR/KzE JOINE, STERN, N05 Histopathology + No MiAcroLscopAic RAbnormality Observed ssesas nTKeiirTmTnienda"lo1n8saSDciargyinte+dic5s6ete trom necropey Gross Pacholony ~~ wo sK"mLOeIRrVEoEARs,.copBKRtIADeTNKEM,YmSo,GrPeILaUNtNAiGLSc,yCORMoDvE,sReErS,vHOeMdSNKGE;HL:ETDALUOWDSECNLE:,SSEPLTEABN,, OHLOUDRNEN,,RSAPLGATLNACGNRAEDRASYS,,GLSACCNIBDNSUT,I,CMNCAEONRLDVOIERB,.ULAPRERICTHULUIYNTM,APRHYNNEOGSDLIEAI,NEDR:TIHFGILLS,H SPTUEAAAIRIRINONALKLD/LVGALEARSNYIDNC.HL,E`SP,BAYRUEA(RTSIH)NRAOWRTIYTDHBLGALODAPDNFEDLRSC,, NTETRERVSAETC,EHSE,AS;KIENPE,ISDOIPPOHRWAOMGSIUTOSAE.TSE,. ERRORS JOE, STERN, TOG Histopathology + No MiPcroAscopRLiAc AAbnormality Observed : DuPont-11414) --_ CorMPany Sanilized. Doss not cont-ain TSCA cay -= H-25134: Four-WeekInhalation Toxicity Study inMale Rats --~ Individual Anisal Pacholosy Data Grow: 3 concentration: 0 mam Sex: vales Aina Rat Wicroscopic & acroscopic Findings Gina Rieraemiindnaal{o8nsBsaaicygrinfeidc5eo6te trom necropey Gross athotosy + So MaK`LcOIRrVToEAsR,,copBKiRIcADINNEA,YbSm,PoIrLNnAaANiLGSt,CyORONDbE,sAeRr,vSYeOdSNKAEG:KL,ETDAULODMEUNSUCMLE,,JBSSPULAEREYN,, ARIOOLDRESE,S,ALSAPGLALINACVNRADERSNY,S,GSLCCAINEASCT,I,CWANCREORLDVOIENB,,ULAPRRIETCULHINYT,AERYMNEOGSOELBNA,PKEDRTIHCISLY:MPH SPTIAETAARRONLLD LGVLERASINNCDL,,ES,PEAYREUART(5IH)NYAREROYITDHBGLLAOADPNDTDEISRC,, NTETReRVsAEtC,iHsE,AS,KIENPB,IODOPIPIORAOWCSIUTOASEC.SE,, PRR/KEE JOIN, STERN, Hog2 Histopathology No Microscopic Abmoreality Observed : DuPont-11414 --~ CompanySanitized.Doesnotcontain TSCACBI Tio HZ:2S513:4: PFoouurr:WWeeeekkIInnhhaallaattiioonnTTooxwiiccitlyySSttuuddyyiinnMMaalleoRRaattss DuDPuPoomnte-l11i4d14d -- Individual Anisal Pathology data Group: II concentration: 5 ma/m Sex: Males Anizal Raf Microscopic & Macroscopic Findings " Frey oKBixrpiaoiisenndarloenGSrdaoacuyrpif:i+c3e5Act TT Raina Ls signed of zon necropsy Gross patholony + xaowerhsumaion, Ric. No MLS(aCIPcBVIrCENoORAMs,,LcoCpCLOOiNRLcGDO.SN"A,,bSoW"TrROEEsUACAaRTCUl,HMi,,ySWKDEOEUGbLOEsEDNeTETrAENvLRNeL,WdCU,SS:CLELYEIM,PNHS,RPLOEIDEELN,ES,AAOLRIPTVAANA,CRAYZBARSA,IN, `SPCALITANADTTSLH,CYROJNeRAwDNvDEGI,LBAONLPDALSRT,OLITiTRWAAERCWYKENGROL,DAEN,DS,SOTPTMAAAVSGRO,OSE.DADGSLRRAEANIRDAY:LI/GLLAANRDASI., EURVIENSA)RYKIBTLAHDDOEERI,CTNEESRTVEES,, SEKPIIND.IOSWRIOOSRTSAR.E,FESGRA/KLNESVJESOIECL,ES, Histopathology, PHAR YIRDPRLEOARNPIELPRAHSRIOAS/ISSQ,UAURNOIULSATMEERTAAPLL,ASmTiAn,imamli.nieal. --~ ssisas TlBeoromesiunraeel GstraoctrpifC:ic5eSic) Roinal is signed off tron ecropey Gross Pacholony "DILATATION, RIGHT, id. No M"SaLPcIIrVoNEsAR.cLopCTOiiNcNDG,SA,bnSoKTErOAMsRAaTCl,Hi,tSyKDOEObLsEOeTrADvL,eWdISS:CLEE,CUSPLETELN,E,AORATRAC,HEBRRSA.DY, CGSBCaCIUNsMT,,ICCSONLAeOwDNv,Ea, "ARPBRICTTGCMLI,TiAWRFEYGNNGOSLDAEENR,DI,CM,ITNILIVISRN:ON(DAKOGRDLEEA,NADL,SALGILAVNADRSY, PSUYRAEIR(NASAT)RHYYWRIOBTILAHDDDGOELPRAT,NIDCST,KEESRTTVERESA,,CKESERKP,IIND.IBOSVOFNPRIIOOASEGTSOA,SGE,,FHESAMREUYMRII/ZNKL.E/LSAVRSEIS0YIX1C,L,ES Teme, ose Histopathology + PARENHEYFDLARROAONRPEAD,THHRYO,S1SC,HROONNIILCAFPERROAGLR,ESSmIiVnEi,ralmild. INPERPLASA/SQUAKOUS ETAPLASIA, mininal CompanySanitized.Doesnot contain TSCACBI ~~ ists H2:22531%34:: PFoouurrW-eWeeekkIIntanlatohnTTooaxiiccliityySSatuuddtyyiininMMlaoelReanRtass Pi. Sndivicual Animal Pathology bate Grow: I Coscentration: 5 mg/m sex: Males nina] Raf Hicroscopic i Macroscopic Findings Gsisas TKielclaeidnalonSabcuryif: i3c5e - AEnxipsoaslureisGsriogwned+ oafcfttrom necropsy Gross rathotony + weaveDsILI ATION, RIGHT, mild. DuPDoumPeoinlti1d1l41d4). `DISCOLORATION, TAN, RAISED, RIGHT. 7 MM DIA. No MaLScIPVrEoIRsN.coCpLOiNRcDs,A,bnSHToEOrAUmARaCTlH,i,tSyKDOEUObLDsEEeTRrAUvLNe,NdUSJCELSEU,RINS,PLETELV.E,AOPNAEN,CREBARSA,IN, `(SCLCEAICNNUDTNS,L,CCJNOAeLNwODv,IeS,URLEPACRIT.TOUMLI,iTvANeREnYGENGNOLDTAEED,R,LCTTHILUVYRSMOP,LHDHMOGODLERA,NEDL.SAGLLIAVNADRSY. EUPRYAIERNSAA)TRIYRWOIBLTLDAHGOOGELPRAT,NIDCST,HEESRTTVIRESA,,CHEFSAKE,IMNI,RE/SORBRNRKEOASEGTYASSRoE.r,inP,SHEAMSRISMNENRLLMV,AESRNI,COLSEES Histopathotogy + rPAaRmNsDRLOANERPRHYROSIS, UNILATERAL, mid --_ EProI`TNSWPeIEERDRPSwLoAScILAE/,SQUmAilKdO.US METAPLASIA, minimal ssie30 TKEexirpTmoiisenudarleonGsbarucoyrwifi+c3e5Bact ATER oR otf trom necropsy Gross pathology No Macroscopic Aorsality Observed + AOAIODDRBERT.A,E.LSKPBLRLAANIAICVDNRA,ESRAY,SS,GPLISACCNNIACDNLSUF,CL,OCRNDNAC,ENORLDVOISENBT,,IOMLAARPCERIHCT,TLUUYXDMMEU,PAOHRDNYEENNOSGMDELNEVA,,TDEJ:RFEEIsCVuEnLe:i,b TSPHUEIARRIIOILNGD/CVGAELRSAIIDCN,L,ESB,SAYAEUR(RHSGY)RRAOWRTIYDFHBGLOLAADPNDTDEISRC,, NTETERRVSAETC,EHSE,RS,KIENSP,SEODPPIIADAOWGSIUPDSAE,TSE,, EAR/KNES J0INF, STERN, NOSE tstopathotegy, No Microscopic Abmormality Observed CompanySanitized.Doesnotcontain TSCACBI -_-- Tie H-25134: Four-Week Inhalation Toxicity Study in Male Rats Po Sodividual Anisal Pathology data Grow: II Concentrations S mom Sex: Males Aina ret Wiczoscopic & Nacrossopic Findings " " per TKEeixrlpmloiesnduarleonGsSraaocyurpi+:ic3a5SacI Tr or Aalnal Ls signed off from necropey Gross pathology + No MAaEOciKirTmoARs,,copKSRiIADcLNNEA,YbSn,SoPrILmUNaNAlGLiSt,CyOROHDbE,sNeNrSEFvOeWdSAKGE:HL,ETDALUONDUESNCLGS,, TSSPLAEREN., OASODLREBE,A,ALSRPLGAILNACVNRAEDRASYS,,GLSACCNIBDNSCT,L,CMCNOOENLROOVIREB,,ULARPRRESCLUHIYMEM,APRHYNENOSGSBLEVA,TDE.RFIICGSLY.Hb TPSEHEAIIRRIYONLADL SGVLASARINICDNL,E,SP,EAYAEUR(RHSIY)NRAORWTYIDTHBGLLOAADPNDTDEISRC,,NTETRABVASEC,HTE.RS,KIENP,ISSDOIDPDAHWOANSGITUDASE.GSE,. FRRR/KES JOIN, STERN, W062 Histopathology + No MBiEcrAoRsTcopLiAcIANbnormality Observed asian SEiexrpmoeisdnuarleonGsbaracoyrwif i+ c3e5fact AIR La Sime off trom necropey. Gross pathology + ~-- No MaLHcOiRraToAs,.copKSiIAcDINNEA,Vb,noSrPmILaNUNlAGiLSt,CyORHODEb,NsNeErS.vTeONdSAKGEHL,ETADLUOMDUESNCNL,E,JSEPSLIEAEANY, OTNODRUE,AELSPAGALLNIACVNRADERSAY,S,GSLCCAEINCASUFN,I,CWACNNOELRDOVIYEB,,ULARPREICTTLUUIYMTN,AERNYHNEOSGDELEYA,TDE:RVLIC SL,b TSEUEAIURNYNOAAIRLD)CGVAELRSAIIDCN,L,ESPB,AYREUNRT(5LH)UYARWROIYLTDHBGLLAOADPNDTDEISRC,, NETTRREAVSCETK,EESR.S,KIENPE.ESODPIPHORAOWGSIUTDSRS,ISE,. FMRKEE JOINT, STERN, OBE Histopathology FrmYPEaRnPLASIA/SQUANOUS METABLASTA, minimal Dupont.11414 ~~ _-- CompanySanitized.Doesnotcontain TSCACBI Tie H:25134: Four-Week Inhalation Toricity Study in Male Rats ~~ DuPont-11414. Individual Anisal Pathology aca Group: II Concentrations S sam sex: ales nina Ret Nicroncopic i Macroscopic Findings - Eh iectaeindalonsabcaryif: ic3e5 -------- AEnxipzoamlureisGsriogwned+ oAfcftfron necsopay Gross rashotony + Ho MLAaIcOVrREoTRsA.coBpKAiINDcINNEA,YbSm,oSrPeILaUNNlNGiLSt,CyOROMDEb,AsReErS,TvOeMSdAKCE:HL,ETADLUODWEUNSOCNLE,,JSETPTLA,, NRIOLODEREGE,N,ALSAPGLALINACVNRADERSAY,S,GSLCCAIBASNT,I,CMARCENORLDVOIENB,,ULARPRIBTOLURYINNT,PAHRYMNEOGSDLEEAN,NTDE:TRIHCOSL.i PTSAENUIRIRINOAI)LD GVCLEAASRNIIDCN,L,ESP.DAYREUK(RTSII)NRAOWRIIYDTHBGLOLAADPXDTDEISRC,,NETTRREVASECT,HEESA,S,KIENEI,SOOIPPOHRWAOGISUTDSAE.TSE,. FEMURKEE JOINT, STERN, NOSE Histopatrotony YPERPLASIA/SQUARCUS METAPLASTA, miniral. seis TKEeixrlpmloiesnduarleonsGradocaurypit: i+ 3c58eac1 Anieal io signed off tron necropsy Gross athotony + No M`KaLOcINrVToEARs,,copKSiRIcADLNYEA,YbSn,oSrPmLaINlCNiSt,CyOROMDbE,sReErS,vTeOWdSNKGE:HL:ETDALUOWDUESNCNL,E,SESSPULREGEANL, ANIOLCDEER,,ESAPGLALINACVNRADERSAY,S,GSLACCNIBDASCF,I,CMACNNEORDLVIOEB,,ULAPRREICTHLUUIYNTM,APRHYMNEGOSDLBEAU,KEDR,TIHYGHILS,H TPSUEENANORAZYLD) CGVLEAASRNIIDCN,L,ESP,BAVAEUN(RTSIH)NYARWROIYLTDHBGALODAPONTEDISRC,, NETTRERVSAETC,EHSE,RK;IEXME.SDOIPpSHRWAOIGGDUTESA,STE,. FRR/KNEE JOT, STERN, NOB istopatholoy PERPLASIA/SQUAMOUS METAPLASTA, minimal `CompanySanitzed. Doss not contin Tspcar --~ TB -- 22H23S113344:FFoouurrWWeeeekkIInnhhaallaattiioonnTToonxiiccSSudyuiinnMMaadlleeRRyaattss______ Individual Anisal Pacholosy peta Grow: 1x Concesteation: 5 mr sex: ales minal net Wicroscopic Macroscopic Findings ses R Se eripancateee s rrheiletyidc+ soSafc trom Tr necropsy Gross zatnotogy 50 MAEaf OcERrTRoAs,.cg opBRicelipPismOoSrPsILaRiiAsiLc,yConaodrb,s.eorSvedsrxeSowneee:,JsEneSs.. TSS0oR08nO.aDlSALCCIiVIAsRY, GsSLAeIaiSaNe:RicOWImNDDyIeCB,oULsAS,RiroLTrioiaatctueeRROG,DoEa,ElS:ToAmSAS,, SFPAEARREgEVsAERISSNKNT,,,BYnSS(ERi)EnW,IRYBTaGOsPRETsLC, NTEREISET,ES,SKLEkR.LOPIROONSTIAOTNE., Hissopachotons RFERPLASIA/SQUNKOUS NETATLASIA, nina. asters R sSeeproirenE ees GsuL icriotiic arom recov -- Gross eacholony No tacroscopic Amorieay Onserved + LRoEnEen,: BiRAgN.,SPcEoRcC,ORCDluSh.CRRRCHe:cBo.ODWEESETJALECTRLO.H Ronin Giauds, SCINC NERVS, PIRI GLAD. ian a, BSE) WET OFC NERVE, SKIN. TROSTRES, [r-- 40 MiTczaoscroptac Anbmorsaliy observed DDuubpoonnit1i1d4i1s4, cOMPAnY Sanilzed. Dogs ney,oontainTscacy --_ we SH:E25134: TFoouurr-WWeeeekkITnohvaalaltuitoonnTTooxxiicciltyySSttuuddyyiinnMMaalleeRRaatsss DuDPuopomnetl-1i1d4i14d.. --~ Individual Animal Pathology Data Group: Ir concentration: S ma/m sex: tales Anica ret Microscopic acroscopic Findings = seit TKAaeiirtnmiaielndalo1n5SsaDicagrynief:dic5oett tron ecropay - RES Gross ashton + Ho MLHaOIcRVrTEoARs!copKBiRIcANIENAY,bSm,oSrPmILaUNNlAGiLSt,yCORMODEb,AsReEr,SvTeOdSMKACE:KL,ETDAULODWEUNSUCMLE,,JSETPULNER,, ANIOLDEDEG.NR, SAPLSAILNACVNRAEDRASYS,,LS0CC0IBA8NF,I,CNACNNEORLDVOIENB,,ULARPREITCLUHIYNTM,APRHYMNEGOSDLEENA,PDE,RHSVGSW:P PTSAHDIHRRIIONLA)DL CGVALERASININDCG.L,ESE,PVAEURRN(5IT)NIARWROIYITDHBGLOLAADPNDTGEISRC,, NETTRERVSAETC:EKSE,RS,KIENIE:SDOIPPDHRMAOMGSIUFSSAE.TSE,, FRRKES SOT, STERN, NOSE ssi oAKnriiTsmiiaenldalo{n8sDsaaicygrni+efdic5eo6te trom necropsy Gross ashology No MaLHcIOVRrEToRAs,!copKBIiRDAcNIENAY,bSn,SorTLmAiaANlLGiSt,CyOROHDbE,AsReErS,TvOeNdSAKGE:HL,ETDALUOWDSECNLD2.,ESSeiRem,y, SUR0O0FR8E.RALSAPGLALINACVRRADERSAY,S,GLSACCNOIDCASUT,NI,CMCNOEoTRBuVEU,,LAASREECTHLUULYNTM,APRHYMENSOGDLBEAV,NPDS.RFIHC SL:b ~ TSPHAEIROULKCGVAELRSAIIDNC,KL,ESP.EAVSEUA(NTSHN)YARROWYIIDRBLGAOLDAFDNELDRCS,, NTERRRSVAECT,HE.AS,KIENEP.SIOOPPIHRDAOWGSIUTDSAE.TSE,, FERMIR)Kes SOIT, STERN, NOSE ~ _-- `Company Sanitized. Doos notcontain TSCA CBI Tie: H:25134: Four-WeekInhalation Toxicity Study in Male Rats --~ DuPont-11414) Trasvidual Animal pacholosy Data Grow: TI Concentration: mas Sex: ales Animal Ret Microscopic & MacroscopicFindings fry RTKeiarTiminioandal{o8nsSDaacjyrnietdi'c5oete trom eT -------- necropay ross pathology No R`aLOcIRrVToEARs..copBKRiIADcINNEA,YbSm,`oSrPmLIUaNNlAGiLSe,yCORWODbE,sNeTSr.TvOeMSdAKCEH:L,ETDALUOWDUESNCLME,, JBSSPULNEGERNY.. AOIDLED,ERSFALNLNIACVDRAESRAY,S,GLSACCNBIDCNSUF,NL,CMNOCWEOORLTVOBERI,,LAPRRI.BTCULHINWT,APRYNNEGOSOLBRAT,NEDR,TIICSL, W TSHAAEVRMRVIIONCLAKDL)VLGALERASININDCK,L,ESP,SRYAEUT(RHSIY)NRAOWRTIYDTHBGLOLAADPNDTDEISRC,, NETTRREVASECT,HEESR,S,KIENSP.SIOOPPIIRDAOMGSIUTOSAE.GSE,, FER/KES JOT, STERN, NOSE stato AKTneirismeio?naloisnsesDciurgyin+teidc5e6off from necropsy Gross racholony + No MRaLocEuVrtEohRs,.copBKiRIADcIUNEA,YbSn,oSrPmILaNINlAGiLSt,CyORONDEb,AsNeESr,TvOeMdSAKCE:HL,ETDALUOWDSECNLNE,, RSIPLUEMEN., ARSOOUORFEB,H,ALSAPGLALINACVNRADERSAY,S,GSLCCAIANACSTM,I,CYNOCNEODRLIVOBENU,,LAPRREI,CTTULUIIMT,AFRWYENGOSDLEEAN,KFDE,RTZHCARL.ard -- PSTRERAUYRIRYNOINERLD/CVGALEASRNIYDCN,L,ESP,AERYUEA(RTEHI)YNRAOWRIIYDTHSGLOLAADPNOTDEISRC., NET`RTERVSAETC,EHSE,AS,KIENBP,SIODPPIIRDAOWGSIITSSAE.TSE.. PRRR/KTE OINE, STERN, OB2 ssisar RTTneiirsmeaidlnaloLnesaSDciargyinfedic5eo6ct from necropsy Gross patholoy + No MaF`LcOIrNVoETsR,,copKBiIRDcANTNEA,YiSm,oSrPsILaNiNiAGiLSc,CyOROHDbE,NsNeEr,vSFeOdSNKNEGHL,ETADLGODMEUNSOCML,E,JESIPULNEDENN,, RRSOUODBREUE,NA,LSRPLGAILNACVNRAEDRASYS,,GLSACCNIEDNSCT,I,CWANCONELRDOVIREB,,ULARPRIETCULTYIMT,PAHRYMNEOSGDLEEAW,NPDE.RTIHCOULS.on SPTEHRUVAIRRNOYALKLD/CVGEALSARINIDCN,L,ESP.EAVRUEA(RTSIH)NYARWROEYIFDABGLLAOADPNOTDRISRC,, NETTRREVASCETH,EESA,S,KIENEP,SIODPIPADRAWOCNSUITSDA.ETSE,, PROR/KUEE JOIN, STERN, 02 "PANYSET,Dogsmy.contain Tey,car TE H25134: FourWeek Inhalation Toxicity Sty in ae Rats Dupont-11414 ~~ Individial antral sachotosy Data Grow: V_concemracion: 30 mg/m sex: wales Sein Ra isroseopic + macrossopic Fiasings a Gn SeBeurpmeoisnsancle Gsearcoyrlif1i1+c5e5Sher RSTn RR Red off trom macros No NaIATcOTERrETRoRAsR,,copBKPAtAIANsLCDNRa,SEbA,mSSo,PrLIsCaaNoeiACe,yC,ORoWDbCE,soEeucS,nTv,OeMdSARxCEuHCe,OnNAD,LUOEsDSEcERNrNT,,ERTLSCReSLv,,h F0iT0AR2nO.RLlSRSACCCLAIIiRVIDAaNR:E,Y, GaLSEsAYeaENi(SRa5,R)ccOXWLARIDDARTRDCEOU,LPLTARIRSC..ENLTETRRHPVAEEC,KREOGSRDLIEAX,NS,DR,OTPPIIRAOSGGL,ISN,S, SFERECR/EVEESiScOiRiEs,. GSAEROE, BLAboS, TRSRES, ERIDIOWIDES [r-- 0 Miczoscopte pimormatity observed sates npEeirpmvionasl sacriice cio: suet AERA a" luhed oft trom neceopey Gross pathotosy : r No M"SaEOcLLUeEESoENAaR,.copBRatARiccAbhKaAi,msno,SSr,moLaTColLieBc,,yCORowDCse,osaLenorS,NTv,OeMdsAAC+HRx,Ce,SUwMSEsScEBu,VsR,SRSLsSCmNLi,,npH HOSE. SALIVARY GLAS, INDIAN LW SOB, FARA, OSTFTEAEERREGVEELSAIJD,Co.LiEeSP,,RBRYKNSEIiSAri)YaiRnOW,eLIDTHBGHiOaoLbmAPoSCt,, NTTERERASVCTEHEESA,S,iEhBR,RIOCTPIAIDOCWGOIESSAE,TSE,: Hisopatholosy RTERTASIA/SQONOUS ETAPLASEA, wintzal. " Seniized, Doss py,contain Tc, car --~ -------- TiC ------ HL25134 Four-Weck Inala Toxsy StiunMdalye Ras --_ oto __ comcemracions dividuns mad acsatony Sata 30 saw sex: tates Duron 11414 Animal Ref Microscopic & Macroscopic Findings 5 664844. ReHTerrmiIaenalnTmstac,ErisficeSheF:rom merry -- eons rates J PBHrA L ESTES E-- SRo beennsc, , oma, f SR eAeREsASeOENs GR iCe nesTIuE,bTCDT MSENEC i GA, ant Soe, Shorte uaneas. Tis, Bofors. [E-- to Microscopic piporeaiicy Ghoerved soca E esecnL sLuoacErsyciscs1heom nacre --_ Gross parotony OHy ie, Ton S--E--Ske, vac, sme, SF KorEina B Gongs,oil tataEX nEinneLeLOnR: neoa,RA E Rf e ESoCN,aa Sirm, ece ren Aan. emacs, [r---- fC R-------- Cc 1 Sila. Dogg poyLoortan Toca ogy ~ S------------r----ee' H-25134: Four-Week Inhalation Toricity Study in Male Rats --_~ DuPont-11414. Individual Animal Patholosy bata Grow: V concentration: 30 mg/m Sex: Males nical Ret Microscopic i Wacroscople Finaings Gini TEKeixrlpmloiesnduarleonGsraboeuurypic+ i3c5sSct TTT Ae Ta a hod of trom necropsy Gross atholony No MaH`LcOiRrvToeAsn.,copBRiRIcAMINEA,mSo,`rSmPLaIUNlNAiGLSc)yCORWODbE,sNeTSr,PvOeMdSAKCI:HL,ETDALUOYDUESNCLME,, JSBPILUERERN., ANIOLOEDRGENE,,AL`SPKGALLNIACVNRADERSAY,S,GL`ASCNCBIDNSCT,,LCMNCOEWORDLVTOEB,,OLAPARBICFHLUUYTMME,PAHRNYENGOSDBLEVA,PNEDTRIAC SL.ib PSTAEWAARRIOALLD CGVLAEASRNIIDCN,L,ESPB,AYREUA(RT5IH)NYARROWYIIDTHBGLLOAADPNDEDEISRC,,NTTEERRSVATECE,HSE.NS,KIENEP,SEODPPIHRDAOGWSUTISND,EESS. PRAR/KTE JOINE, STERN, MSE Histopathology + IXPERPLASIA/SQUANOUS METABLASTA, minimal sear iZEexicpemodisnu'arelenGsaBrcaoryuit1 i+c3eB5act nial is signed off from neczopsy --_ Gross atholony + Yo MRLaOIcRVrTEoARs,.copSKRiIADcTNNEA,YbSm,oGrPLsIUaNNlAGiLSt,CyOROWDbE,sReTrS,vTeOWdSAKGEHL,ETADLUODMEUNSMCNL,E,JESPSLAERERN., AOIOLDEREUE,MR,ASLAPGLALNIACVNRADERSAY,S,GSLACCNIODCASUF,NI,CNANCYEORLOVOUEYD,,JLAPRREICTTLUUIYMI,ANRYNJEOGSDiESaS,nE,RTIHCLELY.MPH STPUBHIIRANOARELD) VGAELRSAUIDCN,L,ESPE,AVREUA(RT5LH)VYARWROIYIPDHBGLLAOADPNDRDEISRC,, NEFTRERVSAETC,EHSE,RSKIENPE;iSDOTPSOHAYAOWGSIUTDASEI,SE.. ERNE JOINT, STERROM, NOSE Histopathology, RPERPLASIA/SOUAKOUS METAPLASTA, minimal. --_ --_--_-- Mm mm CompanySanitizeq,DoesnotconTtsecaicny 2H:2: 5134: PFoouurrW-WeeeekkIIntanlathonTaTooxxilicciltayySStttuudidyiynioMnaMnlaeloRRaass_ --~ Individual Aninal Patholosy Data Group: V Concentration: 30 mg/m Sex: Males nina Ret Hicroscopic & Macroscopic Findings sini TKeirlmliendalon Sbaucyrif: i3c5e NEaxiorssace1sGsrigoned+ odfcfttrom necropsy Gross atholony No NaLHcEOVrREoTRsA.copBKRiIAcIDNUA,bEm,SoPrIeLNaUANlGLiSt,CyOROHDbE,sAReTr,vSFeOdSWKAEGHL,ETADLGODMEiNsOeML:s,ESSPTLmAN,, OATLDHDREIEER,NNOALLDSPAGGALLNILACVANRADESR,AY,S,GPLSRACCANEIADCNTSUTH,NIN,CRMONACTEONDRLOVOTGENLB,,AIYLDRAPSBRI,CTFULUTYSNEMT,APACHRHYREOERGDS,LEHA,IBDSe,RFbIMHCAGSLs.YSM,PH SPFEAEIRRNI/ANKLGELVEAERSIISNCOKL,EIS,,SYEUS(RTSIE)NRARWNYI,THBHUOOOFSDFERIRC, NTEERVSET,ES,SKIENP,EDPIROOYSNTIADGEES. Histopathology + ens a INPRRPLASTA/SQUAYEYS NETAPLASIA, mininal. sins ZKEeixripsioieondualeonGsabrcaoyrwi:f:i3c5Serc nina Ls signed off trom necropsy ~ Gross acholony No MaEHcVOrERoRTs.AcopBKiRIAcDINNEA,YbSn,o`SrPmLIaUNNlAGiLSt)yCOROHDEb,AsReTrS,PvOeWdSAKCA:HL,ETOALUOWDUESNCLME,, JSEPLNEAEN,, NTRIOHOLDNREERE,,OALLDSAPGGLALLINAACVNNRADDER,SAY,S,GPLRSAECCNENIDCTASGTW,MIY,CRNORNCTREODRLOVOIGERLS,,AUNLDAPRSREI,CTHULUTIYNATN,AAECRHYNSERNGOS:DBLEVA,PBDEE,FROIPCSAGL.USi,b FPASRERUIRINNLOELVEEASKIJICONLE,TS.,BYEUS(RTSIE)NRAWRNIY,THBL0AODgPDTEIRC, NETReVSEt,S,SKIENP,EOIPORWOMSITDRRESE,, Histopathology + Ho MFircarAosRcToRpLicARAbnormality Observed : DuDPuoPmonetl-i1a1i4144. --_ -_-- #29. Dog,"Conta "7TSca, ca ior H:25134: Four-Week Inhalation Toxicity Study inMaleRats -- Individual Aniral Packoloy Date Grow: v concentrations 30 mg/l sexs Males Aina Rot icroscopic & vacromcopic Findings eens EKTxeiprTomTisenudarleonGsrebocaurypit:i+c55eict Cr Anant Ta ahead 05 trom necropay Gross pathology No MATaCciKoEgsR,c.opBKiRIAcDINKEA,YbSm,SoPrImLNIaNAlGLiSt,yCORHODIb,AsReESr,TvOeMdSAKCE:HL,ETADLUOWDUENSICNL,E,JESPJLUENEIN., AOTDLDRE.E,RLSPAGALLNIACVNRADERSAY.S,GLSACCNBIDCNSUT,NL,CMCNNOEDLRIOVRRES,,LA`RRPEICTHLUOXPNT,AHRNYENGOSDELEVA,TDE,RTIVC SL.YMPH "TSPVAEARROALLD LVGALEASRNIYDCN,L,ESP.DRYAEUN(RTSIH)NYARWROIYTTDHBGLOLAADPNDTDEISRC,,NETTRRoVAsECc,HaE,ASKIENPB,ISDOPIPRORAOWCSIUTDASET,SE,, Histopathology + suns IRPLEaRPLASIA+/SQUAKIUS METAPLASTA, aininal. asss TEKeixrTpmhoiosnauarleonGsrSaoacuyxpti+c3e5ct AEA aE Rea 086 trom necropey --~ ross sacholoqy No MaH`LcOErRVoETsRA.copDKiRIADcIVNEA,VbGn,oSrPLmIUaNNlAGiLSt,CyORoEDbN,sRerS,vTeOMdSAKCEHL,ETDAULODWEUNSOCWLE,,JESPSLUEREMN., RSOLDEE,, SAPLAINCVRAERAYS,GLACNO0GSN,, MCDOTLBONU,LARRECRTUYNH,PHMENOSDEEN,TERTIACGSL.WP `PSTAEHAIYRTRNOLAIXLD RVGLEVASNIRDC,L,EPSA,ERVAUET(RHEIY)NRAORWIYIDTHBGLLOAADPNDTDEISRC,, NTETRREVASECT,HEESA.S,KIENEP,SEODPIPHDRAWOGMSUITSDA,ETSE,. Histopathology, ns INPLEaRPLASIA/SQUANOUS NETAPLASTA, miniral. DuPon-11414. --~ --_-- 20n80t8 gop, in Toca car 1125134: Four-Week Inhalation Toxicity Study in MaleRats ~~ Individual ansead suchotony data Grow: v concentrations 30 mas sex: Kale Dupont11414 Animal Ref Microscopic & Macroscopic Findings o 664852 JdTeromeirnandl SyaA crifi5c0ePp -- or Gross sachotosy : So MRaTEcvLozaEonns,:coppBRtieiocaunaAtrbsem,o,SromTiaCOnlNosiEct,yC,onJOdCbE,sWoeSSr,oSvoeuSdAKRCEo+hL:cEhTAD,LIOWVEDSSELB,T,EAJLSESpSiLgUa,A, nS0FiOor0RetEhLSCRGCLaIInLNAisGRn:S,, CEBSALOSAISRN8,IT)IRCOWWLNAEDENPRDVAIEGIR,TLDAPSERLTNUDTELIIRABASSAR,KYREOSGRDKLSiA,kED,S.OSPPAIAAORGGIEESA,FE, FEEmRREVESoSre,n, ASkRaEn,BHiooasn, TaStis, BSiOToMESES: sscnst Jf-- erin-- g] -- prespa-- J oErRnR.: SRainm-- te,SeiTaOnNsS,C-- onJdE,ANS,ToSuXEEHL:UTADLIwOScDLEE, SSHeIigRe,, -- SoTLOeER,ESDHGALLNTAaAER,,CLSiCCtIhoNsoE,LnCWAGAoNSvDAaIEnR,,SLA$ARSLCTTOTuLINIG,AARYHREOGSDLEH,AEDATLAe PTEn ROLE CNS: shsamnotD SLkiSS, Ties. ESoPiAGLS. TFSiEaEAnLRCVEaSISnCOL,ENS.,SUUSSRSED)EARRWAYE,RBHiGOaRRbEIoLsG, NTEREVoET,ES.SKIENS:IDFIAOORSPORSCSE,, asasst JB p ooR s--L-- -- cross sathotosy 0 Naczoscopte pbmoraality observed : RRNooEna: SBPLaeNncAkiiYnsS,GeCauonb,oC.onNeSByoIoB`nSI,TLOvASARCpHe:LkPB,NVOFEORSED,BSETEoGAsHLN, A TEoRtAENsG VCCiRAaSRoII:C,iRks(AG8TIR)AEOWYLEDPBGiPaLSpAoENiCS, VBTERERSAETC,EHSE,SRKIBNSE,SIODPFIIROAOMGGILTOSAE,CSE:. Fin sos S00, STEN, W008 go PYSanta,Doesnr,ontain 7- 50, ~~ cay Toe H:25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont11414. ~ Individual Animal Pathology paca Grow: v concentration: 30 m/w Sex: wales nical net Hicroacopic i Macroscopic Findings Tr Gans AeKiirlsalaienldaloinssabsciurgyin+feidc5eo6ft trom necropsy nse Gros pasholony + ameTsHLATATION, RIGHT, severe. No MSaLPcIVIrEoNRsA:cLopTCiOOcNRGDS.A,bmSoNTrEoNWrRAaTCl,Hl,tySKDEoULbOEsDTeAErLvRe,dUSJCELES,UNS,PLETELN,E,AOKPTAAN,CRESAASI.N, CGSECLCIAUNNMTS,I,CCOJNLEDORINV,EB,O"LRPAEICRTTUUMIL,TIAVMREEYRSGENLNOAOTREED,R,IRCTLHSYIR,NOGLDRAGDOLRDAEENNDA,LSAGLLIAVNADRSY. PEURAYIRENASAT)RUYYWRIOBTRLAHDDDOGELPRAT,NIDCST,EKSETRTEVRSEA,,CKESERKP,IED,EISOOPWPRIHOOASRGTSUA,SS,E,FPISHMHNAA/RNKYAN/LELSAVSEROSVNIKNCEL.ES, Stes, 082 sues TAKeinrlimlsie?ndalon6ssaDicayrgin+feidc5eo6te trom necropey ross ashatony + --_ No M`HaLOcIRrVToEAsR,,copKSiRIcADTNNEA,YbSm,o`SrPmLIaiNNiAGiLSt,CyOROEDbA,sEerS,vTeOMdSAKCEHL,ETADLUONDUESNCALM.E,SSEPLNEE,. ILE PNKCREAS, CBC, COLON, RECTUM, MESNFEALG. LPH HATOIODIRERE,OAILD`SNGGLLLIAAVNNADDR,SY, G`PSLACARINAATSTH,IYRCOWIANDRE.RDVIGELS,AUNLDAPSER,TLGITIRTAANCRHYENNOG,DLSA,NEDS,OTPHHYAGSU.S, PSPEHRAIGRDRYN/ALKECVASERSIISNCOGL,EIS,E,VEUSRT(5I)ENRANRNIY,FHBNLAOODSPDETEIRC, NETREVSET,ES,SKIBNI.OIPDRROMSITSAETSE., ~ Doesney,Main Toca cs -- wm SH:R25134: TFoouwrT-WoecekkIIhnhaatlaitoionn TToovxiiceittyySSutuddyyiinnMMoalloeRRaattss -- Group: VII Animal ne Giast Indtvicual Animal pathology Daca concentration: 100 mas Sex: ales Ficroscople & vacroncopic Findings eKEirxinplioensdaelsonGSraDocaurypit: i+ 3c5de ct Reiral is signed off trom necropsy No MAaLOciRvrTeoAns.,copKAtIAcOCuNEA,YbSn,oSrPmILaNNlACiLSt,CyOROMDEb,AsReESr,EvOeWSdAK:CEHL,ETADLUOWDiESNCNL.E,JSEPNLNEEAN., SNAORUDEEN.ALSNPGLRLIIACVNKADERSNY,S,SGCLAICNOADUTSNI,,CWNACEOKRLDVOIYEB,,ULRAPERRCTTLIUIMIT,ANRYNNEOGSDLEEAV,NTDE:RFEOC RL.b TASBHUIRIONIYA>L AGVLENASNI,DC.LESP.TAYAEUN(RCSIW)NYARWROIYITDHBGLOLAADPNDTDEISRC,, NETTRERVSAETC,EHSE,AS,KIENI.ZOSIOPDPRMWOAMSGITUDSAE,TSE,, FEMUR)Koes SOI, STERN, NOSE Histopathology INPLAGOTION, SUBACUTE/CHIONIC, FOCAL. minisal. No MiKBcRIADrLNoKEs,UcSo!pSiPcLIUNNAGEbSn.CoOrNHeDEa,AiRiTSc,TyOWOSAbKCsEHeL,rSvTeDAdLUOM:UDSBCLAE,JSEPNLNEEAN,, AIGLROA,, --_ GPSLRAAILNCIDRVSEA,NRSY,SGCCLIANBNTNDISC,, NWCEROAVLUEOD,NI,SUPLRIATERUCINTL,AIRVYEMGELRSAOENDNDET..SARZTIEVVLRGOi:LNDiGANLDRAoEDNt,AL PARNTITAOLD GLAXDS. THACHER, SEOPWAGUS, PHARIN/ARNE, RSEYIT3NE(ARSR)NY,WBILT"HASDOENFRD,MIACRRTONEWES,RTVEESN,,OSEESKPIIND,IOPWRIOOSRTSA.RE,FESMEUNRI/NAANLEEVJEOSIICNL,ES. DuDPuoPnoenlti1d14i14d. --~ "200.Dogsney,<ontain Tsoca ogy Ts- ---- Pe. Z2F3-205313%4: oFouurr-WWeeeekkIIonhhaallaattiioonnTTooxxiiccittyySSutuddyyiinnMMoalleeRaRattss Individual Animal Pathology data row: VII Concentration: 100 sam Sex: Males nical Raf Microscopic & Macroscopic Findings oT Siess ieErxepmoidsnyaclaonGsrSaoacuyrpi:fic3eS5 ac ATES hed off trom necropsy Gross rashology No MH"aLcOirRvoaTsnA,copBKiRIcADTNNEA,YbSm,oSrPnIDaNGlASiLt,CyOROKDbE,sNeTr.vSTeOdSUAEG:LHE,DADLUOWDSECNLNS,,JSEPLNEEN,, ARIOLODEREUE,MA,LSAPLGNILNACVNRAEDRNSYS,,GLSACCNIECAECT,I,CYANCNEORDLVIOEB,,ULAPARIBTCLURINAT,MAERYMNEGSSLEBAN,NTDE:TRHICAILSw,in STPEAHAVAIRRYNOIALGLDHLVGALEASRNIDKC,L,ESP.EAVRUEA(RTSIH)NYARWROIYITDHBGLLAOADTNDIDECSR,, NSESRREVAREC,HSE,RS,KIENP.SISDOFIPRHOAOWGSIUTSOA.EVSE,. PRRKame JOIN, SPER, NOSE. Histopathology, POt AAR RPrELARaPReLIuAeSiIoAn/,SGUsAUNBOAUCSUTEH/ECTHARPOLNAISCI,A, FOCKL, minisal. mineal. No MB'iKRcEArDIoNNEs,VcSo,SpPeILUNNAAGbLSn,CoOrRmNDaE,AlRiYSt,TyOMOSAbKCsEHeL,rEvTeADdLIOMUDSECL,E,JSEPSLEUR,N, ATOLRTEA., ~ GSPAALLNAICIVRSAE,RSY,`SGCLCIABANTDNISC,, VEMoRAuVDOEIR,S,UPLRIAETRGVIIOLENNN,KREYNWGELSMAOENDVDEP,,ERTTEGYHRULOSLP.)HGAMLDoARoNEsDN,AL EamaciaoTy Cus, Tack, toons. Ea) win orric SoarReRosN,,"ERr0T5b8IomiOES, FER/RNES SOLVE. STERN. BONE DuDuPPoonnte-l11i4d1i4.s ~ - "eaeBongnr,contain TScacy we $2134: Four-Week Inhalation Toc StinualdRayts --_ Intividund I dnieat Pacholony -- Daca Seine ar Nicrouconic + saccoscopls Findings Geen SE Sfeermpianrarlas ste aocrrite iceact-- Gross rathotosy No toSarcverewonnis,,copRSgiacinbpegmuoScsmenaaetnsscT,yoy SonhbsOeaSrvheSdocuhuBm ovanc,SsmEe, FRATOiRBRnEeEaSACGLaIOuVNvAsR:,Y, sGSSaeuRemEaksc)RiocRRMODTRSN,TkLAiRPRsirvLoAiEeoCaYmRerMnSGOoiRnr,Eoks,FoTmIieo,tuse,. FSRERMAius iSo:t CSAhTiAeRnY, Laageo. 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Compan"gy,M24,Dogg _ --_ Contaty Tseqcar _---- oo ,-- 2112255113344: FFoouurrWWeeeekkInIhnahlaalattiioonnTTooxxiicictySSutuddyyiinnMMaalleeRRaattss__ - Individual anise Facholosy Data Grow: vii consecration: 100 mam sexs ales Sian red Wicroscopic & Macroscopic Findings Gai Eferrmbiitnbephcsraacmrpi:ficefact I ET hed 212 exon mecroey Gros sathotogy Ho MaRLScoEienoRevs,,copBRpthisacbnaaAinmsso,,SremiTackinhiiGocuyG.oWoGbnEsoeoRrSvTnOeMsSAAKCbsHLc:EhT:DN,IEwOuSsDHciEEzA,LSGsS,pSiLaRmA,,H iRRFOOADoRREilnLSKCCGaLiivaAais:Rn,, GsBSrLeAAEAS(R5.I)RROWWRRENDADRYICSODL,FLAEADSSRGEESNLGETEiRSmVAAEbR,HYRASSoKBLIRkD,O,,PTEPHARCOEGS,R.ES, FSErALeVESisCotuvirs,, SHirtiaonny,BHAobooR, TEStES, BSLOIOVIOES, Histopathaioay rLssaATIaN, SUBACITECRONE, FoCK, sini. res)oTreitmisnwaGkeerse1m08yRees, --_ Yo MSiTEcRrEAoGscTBo.pGieeCClAaiemcooCr,onrnadCi.soiu!tSny,omSaAoeEsSe.CErHvNed:doWovEsSePs:AR,ENsSsaGwaoLm:A,AsMoODmE,, SGSALToAISAc.RYiIAeNDTtSE.CeE:SVaRH ,uiPaEa nRULSikEsGRLobae,, TSeRkGaE:D SAASRKSER F{FrIRSai(nn5ck)os,cBeLBnAoDvDeGERPk,aGnTaAEeS,kTVEESo.,stESALSD,OMTIODSETSA.TE,FESVIGNRZINMNELRVETSOICIL:ES, esuehats Sins DuDbupoownecl1i1a4i1d4. ~ 1200. Dogg py Contain r3g,a, ny ETH --~ HdH2s511334%:FFoouurrWWeeeckkIionahalluaitoinonTTooncySSttuddyyiinnMialleeRRatass Grow VII concentration: Individual anizad Bachotony ate 100 mm sexs ales Raima a icra + Wactoscopic Findings Gorn WSSSpeorErEucieRLaorrEiielSaHctrom conn Geons patholo+ 0 sJaoTcvOErenoRR,scoRSEpaitvRionAsu,m,o,SroeTraCoilnosaeccsyCooIoCnbEsoeo,Srnhv.oeupdnReekenu:teinSna TwVEoScRBiesR,ESRsLhemesLar:,m FSTSaoERmnEOiTaALCCaiTEaaAAn:,R,"GsBSaAsaTikOr5S)acvRVwOBiTRmaSC,OLA3RSS1EiSrvLTaeRaAnAB.SaSnahed,rEoo,SsPmnircse.. FFrrEolrRa Sores, Soin,SO00a LR sistopachotony THHERPLARIA/squno0s NESAPLASIA, iin No MoE iFcrvosce opEiR c SAO morsTrag otincsy y SobRseTrvedSy h ue,evocAe, om, _ SRESERoEERnRoEitnDSWACCETuuAs:ON,riCpeSaeosiNaaeTRsaivEcRYoSSrORre:NinsADp,AorSeAoeARARrGeiBECSaSonhn,Eear,PninIeuu:ss,s, SShrena, S"soonewhaSEne,ress,ehSHASomEN, Fane To pDuuppoonwte1t14i1a4s -- -_-- Com,"Stiteng oy, "St Santa in Tica ony or 125134: Four Week Inhalation Toxicity Study in Mle Rats Dupont11414 -- Grows viz Individual anseal sathotogy deta comentration: 100 ear sexs ales Sina nat Hicoscapic & Macrosepie Fisting Gaia elEErerotsia iecnancaoaErlyiiot'dice5of5tufertrom necropey a Gross pachotony No NHaiTocvuLretasaEs.,copEPBiihhcbaeiMirmnso,,GresLiacislnoiscrsc,yC,onoWdbcE,soNeuNrmS,v:TeOdsRAeEcRbt,uimvD.,OwVaREciSEsT,ETsREeSiTs:, DSREoR0onR.tihaSALCCLAtAiIR:,Y, CsBSaLYeAiASTa5,)IcAGWwNHoiADRmDEEGGLR,ASFNLDAPRSR.ENLTEFRIRHVAEYC:HNEOGkSDLoEhA,,EDS:OHPFIRAOPGSIISR,EE. S[EDEALrVEiCLs, ThA Sabon, sts, iOIoMHORS: Histopathotony rIINn PARLIENGSORIAGNSR, ULSUNAPASCUTKE/ECTHARPOLNAESEE,A,PmOiCnAi,oalminisal. TRATION, SUmACUTE/CHRGNIC, minieal -- No MiEEScaRErdoARsicSEo,pSiecTCiiaacstbeon,nCo.ornmmsCaa,nnoieSt,uTyOMoSAbAXCseHRLe:LirEcvRheD:SdOfNSusEEciRsS,SEsBvILeAR,HAJoNaOoTSaAE,, SNSFEiRARvTVaARE:ARCSskIGCiDEL,aACTNISSLC,msNiS,EdRTVT,OVRRASUCFHECIRRh.XksAE:SSRSOIORMCAABhOCMaSEu,E.,: BTEELYARRESA1OO5RSL)R,S,VCTAEELDSSATEDSER,FSATLIC EELDIbrkioes, TEAER Sort, SEEN. Bort IARRGR, HSE ~ --_--_-- BoosnorConte Toca He25134: Four-Week InhalationToxicity Study in Male Rats ~ Individual aniaal Pachology Data Group: VII concentration: 100 mg/m sex: ales Sana Re lcroscopic & sacroscopie Finainon Genes eKErixlpeloiennduardeonGsrabcoaryuipf+:ic3e5Act Aninal To signed off fron necropsy rons Patholony + Yo MIHaOcVRzEToR.s,copBKiIAcDTNHEA:YbSn,oSrPmILaONNlAGiLst,yCOROHDEb,AsReTrS,vTeOudSNKCEHL,ETADLUoWDSGCNLAE,,SsEpLSeHmi,. OATIACELIRER,EO,NILDSNPGGLRLLIAAACVNNRADDER,SNL,S,GPALSRCCAAIOSTAGSTHN,IY,CRWOCNIREODORLTVOGOENLU,.ALNDARPSREE,GTRLUUTFYNRIN,AAGERHYWENEROSG:DLEEAN,RTSDES:RVOIPCSAGL,LSI,N PSFAEAIRRDNIAKL LVEAoSRiJICORiI,iNsT.,FYUSETR(E)TRRWNYE,RKBNiOOASP0EToIEC,NETRhVeEs,is,SKEKR:OIPORMOISTDAEGSE.. Histopatholony RAR NSPNEPARLPNRLBTAASTIIAO/NS,GUSNUKBGAUCSUTEM/ECTHARPOLNAISCI,A, FOCAL, minieal. minimal. No MiKScAErIooNNs,GcSo,pPiEcLAiRAnLmso,CrOmRFaDEl,AiRcSS,yTOMOSAbXCsEHeL,rCvTeNDdLUOWDUSECNLOE,JSEPLSEEUN,, AJOORTNA., --_ GESELAAXANLENCTADRUTSEAH.ARRSY,OSLGCDLICAENNCGTDULISMAC.,NDNSECK,RAOVNLETOO,RT,AHCUPKLRIEEATRCRU,TIOTLRAYE,RHCOYERHKRGEALMSCAOIENDSDNE,.S.EIRDBHCIVYENN(LOO6YS)LM,PWHCAiLKDgAORDEDESN,,FATLIC SEESRTVEES,,SKEIRNl,orRbOnSdToARTsE,,FESIRMTRALEVEJEOCILNETS,,SUeRIiNA:KY BBLOANDEDER DuPont 11414 ~ -_-- Santtizeq p, . "OtContatn rg om 20: H:25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414. --_~ Sraivicual Animal Pathology bata Group: Vil Concentration: 100 mg/m Sex: vales Animal Ret Wicroscopic & Macroscopic Findings - Goins TEKeicrlosliesndsaelon SGabrcuorywif: i+ 3c5dect Naira 1a signed off trom necropey Gross Patholoy + No MHLaIcOVrNEoRs!,copBKiRIcADINNEA,YbSn,o`SrPmLIaUNNlAGiLSt,CyORMoDEb,AsReESr,TvOeWSdAKCEKL,ETADULODWEUNSCCNLE,, JESPILUENERN,, RSODEDRERE,G,AL'SPNGALLNIACVNRADERSAY,S,GLSACCNIEDNSCT,I,C MNCAEONRLDVOIERB,,ULAPRRIETCULKLYNIW,AFAKYMNEOGSDLDEAI,NPDS,RTEHC IESMP STERAUYRIRNOAALLDRVGLERASNIDC,,LESE,PVARRUA(RTEIH)NYARRWOYITTDHBGALDOAOPNETDRIS,C, NTETRERV6AETC:iHSE.AS,kEiDE:SLODPPIUROAOWGGIUPSRSEF,SE., FRR/KSEE JOT, STERN, OSE Histopathology PARKTsNIEVsPRHOiRLOD.PACTLHAYN,SCHRONIC PROGRESSIVE, minimal. `RCENERATION/ATROPHY, SEMINIFEROUS TURLES, UNILATERAL, ~ No MiSLcIPVrIEoNRsA,LcopCLOiiRNcDG,SA,bSmTNoOErMAsARaC,Hl,iySDEOLObEsOTeArDLv,eMdUSS:CELEI,N.SPLEIELN.E,AORFTAAN,CREBNRSA.IN. `CSGCELIACNNRD,SI,CCNSoEtARoNVnDE,L,BU"LPAAIBRTUTIL:TOAHVRPEYHGGENLOVADINESD,K,ITCTHLHIYSRmO.EDNRG5OL5RA,ENAD,LEALTGEILAVACANHRDEYSR, FBEERSMOOUSPTRAAACGNEUE,S,SSCBEOHIAIRNNI,R)SVLETSAEICRRLNE,,S, BEUOVRNEEISN)ASRAYWRAIBHEL,ADODNBEoIRs.E HSEPREVbEC,OMSIKSEEE,. PAATRYROD GLAS ~ --- ComPY Sanitizg, 9. bogs,tenia 15, CY HL25134: Four-Week Inhalation Toxicity StiunMdalye Ras ~~ Tnatvicuad nnseal sathotogy vata I-- Rien rok icroscopic s Macrasopie Finsinge Gaia fR mionmaR l saeS riticeA -- Gross Bathoioy + 0 NaLRacoEnxEenons,,copPSFtwAeiaRtvpAiiSeroS,resTaCaiioneiCt,Cy,onoSsbCE,soNeuTrSn,vR,eodSECRRHa+L:cFDkAS,LIOWNSESSELENNS,F,ERSTsSSruSELRmPy,,H TTHOhrDEanERmo.BIADLSaLCCLoAIN,DY:S, ACBSeCALSTRARR,3)IICR,ORAINAiDEMmRDVCELLR,ABESAESSRSS.TVUTETLIRRIVAANECR:HYERASGOLeLBoA,kSE,OS:TOPRRRAOAGOLTESR,GE. FSoRuRs,nVsESITCoLtiess:, SGABrAR,Y BiWaobootn, TEvEEs EHIOTSREDES Histopathology + Yo MA icroncos pi Amormality Observed + coanen iT ToarmtineL s58sDacerliet'icSnee exon necroney Gross pashotony ~ So MavcrnoscopEtisneAvmso,rmTainioisy MOEsAsReEs,vedSGLETAL WSCLE, SELaEN, ATOoRTkA,, DBRcAnLiN,ndS,PINCAhLoCeONDS,oSuTONNRCHe,chS.UGNEDSERNHEIAECSNLRR,P TENSlREonRaEOrTaSSahCGiikomius,as, CPBSAoYAEgiTSI,)IRAOAWLNoEDENMRSVGTESRL,VGAELDSDAEER,EELTTRANAAECR,ITMSGO.HDLIEAN,ED,S:OA PPIRAOGGUTSR,CE. FSoaogsVESisCoLbiss:, TSRrAiNS. SOb0o8R, TESTES, BRIDTOISES: nietopacotosy 20 MicAraoscopiacaphmoreality observed sssnss tTrertrminre8sMacnriiet'icSeet exom nacropey Gross sashotogy : 50 MHeaocurmnoas,copsRieocauAnnb,mSoreTmraiNloi)zCyonoBdbA,sReErS,vheodSunLcOHTS.oWsocLmE,SsSpLSam,, TSDBoE0EtRsSRHGCLiTaOInnA:sRdS,,CsSRLCAiAoAnSTt,cR,eAGWNLcoDNSoLEuSSC,:SALRABRSR,eLLcAThIGCRHNWERGOSRLEAR,EDHR:OBEMEIEAGL,LSR,P TFEiRnnetCeasnsSeisos,b,,DVSAS5rN) aYw,iSH0OoFooLERE,NETREUSET,ES,ShiSkI,OTFOANOEGISREESE:. nistopathotony Wo Miczoscopte pemoreatiy observed Dupont11414 --~ CompanySanitzed. Dossnotsontan Tac cr = -_-- 25134: Four-Wesk Inhalation Toxicity Study in MaleRats Individual Animal Pathology date Grow: vii Concentration: 100 mgs) Sex: ales Arisa Ret Hicroacopic i Macroscopic Findings Seiaro KRTiealrtlaneiadnalo{8nSaSDclargyinef:ai'c3a6eee trom nocropey -- Gross pathology EvE(s) sam opric Eve: No MSaLcIOVrKEoARs,,copBKiRIcADINNEA,YbSm,oSrPeILaNUNtAGi,St,yCOROWDbA,sNeEr,SvPeOdSRKAEG:HL,ETALDUOMDUESNCNLE,,JSRPTLNEENN., KAIOOLDRREUE,NA,ALSKPGLALINACVNRADERSAY,S,GSLCCAINBASCT,I,CMACNKEORDLVIOEB,,ULRAPERICTHUCIINHT,AVRYMNEOGSDLBEAI,KEDR.TIHCOSLY,HPH TSPLERAAODRSYLEASRK,/CCATLREAISDNT,E,SP,ASEKENIPDNT,HDIYORPWORNOLISDOTNGASLT,AEN,DFSSE,ERARTL/RNKAANCLKEEEVRE,SJIOCIELNSETOS,P.IASGRTUTESA,RANR,Y ES Histopathology : Ho MiBcrRosTcopLiAcRAtmorraliy Observed : soem TKRaeiirTnmiaie?ndalonsSSaaciyrnief+si'c5ae6te trom necropay ~~ Gross patholo + CredoCNC. No MSaLcPErEIoRNs..copCLOiiRcnDs,A,bnSHToEOrAWmRAaCTlH,i,tySDKOEObLOsEDeTIrAvLNe,dWISJCLEE,U,SPLESELN.E,AORSTAAN,REBRRSA.IN, S`GCCEEICNURTM,,ECCOVNLeROwDNvI,eS,ULRABFRCIT.TOONLI,TIAERMRYESCNEONLDTAEEN,R,ITCTIILNVYSRMPO.HLDDRGONDLBEAO,DA:LSAGLLIAVNADRSY, ETEEVASERTSTEI)SV,RNOEILPHDIDIOGOLFWATNNIIDCSO,RNSE,RTVREAF,CEHMEUSNKR,I/NA,NSEOEPMRIGONOSGTTYNASTT,,E, ASSRTYEBIRNNM/,LAVNVEOSSIiEEc,ies, Histopathology + Ho Microscopic Abnormality Observed : DuPont-11414. Comp1a921ny 8BaitizedL.oooes notcontain TSCA oi 306Em,