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SBCcoroEtsAi HetiIt.S tn 608.241.4471 608.241.7227 Fax AR260322 CORNINGHazleton 3M St. Paul, Minnesota FINAL REPORT Study Title: Primary Eye Irritation/Corrosion Study of T-6684 in Rabbits (OECD Guidelines) Author: Steven M. Glaza Study Completion Date: January 28, 1997 Performing Laboratory: Corning Hazleton Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704 Laboratory Project Identification: CHW 61101151 Page1 of31 | FEB -3007 605711 _-- cHCwHeWns1o10u11s51t (COMPLIANCE STATEMENT Primary EyeIrritation/Corrosion Studyof T-6684 in Rabbits (OECD Guidelines) `aTnhdisDsetvuedlyowpamsenctonPdriuncctiepdleisnoafccGooroddanLcaebwoirtathotrhyePOrragcatniices,atCi(o8n1)f3o0r(EFcinoanlo)m.ic Cooperation . StevenM. Glaza Study Director Acute Studies Coming Hazleton Inc. Date A) 2 605712 -_-- cuCHwWeennoonnsst QUALITY ASSURANCE STATEMENT `aTchciosrrdeapnocret whaisthbetheenOrregvaineiwseadtiboyntfhoer EQucaolmiotyniAcssCuoroapnecreatUniiotnoafnCdorDneivenlgoHpamzelnetto(nOEIncC.,D)in PcroinndcuicplteesdofanGdofoidndiLnagbsorreaptoorrtyedPrtaocttihcee,SCt(u8d1y)D3i0r(eFcitnoarl)a.ndThmeanfaoglleomweinntg inspections were Inspection Dates From To 12/03/96 12/039 01/23/97 0123/97 Phase Dose Preparation Data/Report Review Date Date Reportedto Reported to Study Director _ Management 12/03/96 12/03/96 0123/97 01/23/97 Representative, Quality Unit 3 [27.77 Date 60s713 -_ 0 cchwwesntioouuisst STUDY IDENTIFICATION Primary Eye Irritation/Corrosion StudyofT-6684 in Rabbits (OECD Guidelines) `Test Material Sponsor Sponsor's Representative Study Director Study Location `Study Timetable Study Initiation Date Experimental (In-life) Start Date In-life End Date Experimental Termination Date `Study Completion Date T-6684 3M Toxicology Service Medical Department 3M Center, Bldg. 220-2E-02 P.O. Box 33220 St. Paul, MN 55133-3220 Roger G. Perkins, PhD 3M Toxicology Service Medical Department 3M Center, Bldg. 220-2E-02 P.O. Box 33220 St. Paul, MN 55133-3220 (612) 733-3222 Steven M. Glaza Corning Hazleton Inc. P.O. Box 7545 Madison, WI 53707-7545 (608) 241-7292 Corning Hazleton Inc. 3301 Kinsman Boulevard Madison, WI 53704 `November 27, 1996 December 3, 1996 December 17, 1996 December 17, 1996 January 28, 1997 4 605714 -_ Acute Studies Steven M. Glaza MSatundaygeDrirector Steven R. Sorenson Study Coordinator Jeffrey B. Hicks In-life Supervisor Rose M. Bridge Administrative Supervisor `Toxicology Support Kathy Myers Manager SCaulpveirnviLs.oHrorton KEY PERSONNEL Quality Assurance SherrRy. W. Petsel `Manager cocwwenenoouisti Laboratory Animal Medicine Cindy J. Cary, DVM Diplomate, ACLAM Supervisor 5 605715 -_-- cacwwesntoouns CONTENTS COMPLIANCE STATEMENT... QUALITYASSURANCE STATEMENT... STUDY IDENTIFICATION... KEY PERSONNEL... OBJECTIVE sts SB BREY PLEGAULONS ssS s 8 SSJ AnimalDiet ........ m------------------------------} JUSHffoirSPCECaIEtSSEilEoCtnON ee PrepOafTrestaMtaitoenrial... 10 ROeBaSsEIoVnEfHOONrS.R.o.ucte OfAMIRISTAON...m ..s ..m.....oisern1e100 SS LocationofRaw Data, Records, and Final REPO... 11 RESULTS/DISCUSSION ttn 11 SIGNATURE... 11 6 05716 -_-- cCwHeWn61o10u11s51t TABLE 1 2 AveragePrimary Eye IFTtation SCOTES occurs IndBiyevITiBtIdO uSCaOlMES.....vssssseee 13 eo14 3 4 SIodinum dFIUBOi OTdEYSCvWeEinIEiGXHASdM(8M)uBHOaNSl.....r ...crcssrrs rr een1188 APPENDIX... PIO TP20MT2 O vCsOs N 19 20 ProtocolAmendment No. 1 wrer--------"t] 7 6057177 -_ cacwHWen61a10n11s51 OBJECTIVE `fTohleloobwjiecnatgivseionfgltehiesxpsotsuudryewofasattoeasstsmeastsetrhiealrteoloatnieveeyleeveolfoaflibrriintoatraibobni/tcso."rrosionproduced Allproceduresusedinthisstudywere incompliancewiththeAnimal Welfare Act Regulations. Inthe opinionofthe Sponsorand study director, the study did not `unnecessarily duplicate any previous work. All procedural times presentiend this report fall within the acceptable ranges as specified in the Wisconsin facilityofCorning Hazleton Inc. (CHW) Standard Operating Procedure (SOP). TEST MATERIAL Identification `The test matweasrideinta ifiled as T-6684 and described as an off-whiteliquid. Purity and Stability `The Sponsor assumes responsibility for purity and stability determinations (including under test conditions). Storage and Retention `Thetest material was stored at room temperature.Anyunused test material will be returtno tehde Sponsor after issuanceofthe final report according to CHW SOP. Safety Precautions `The test material handling procedures were according to CHW SOPs andpolicies. 5 005718 -_-- ccwaew enn10m11s51 TEST SYSTEM Test Animal Adult albino rabbitsofthe Hra:(NZW)SPF strain were procuredfromHRP, Inc., Kalamazoo, Michigan on October 30, 1996 Housing After receipt, theanimalswere acclimated for a periodof atleas7t days. During acclimation and throughout the study, the animals were individually housed in stainless steel cages. Environmental controls for the animal room were set to maintain a temperature of 19 to 23C, a relative humidityof 50% 20%, and a 12-hour light/12-hour dark lighting cycle. In cases where variations from these conditions existed, they were documented and considered to have had no adverse effect on the study outcome. Animal Diet `Theanimalswere provided access to waatdleibitrum and a measured amount of Laboratory Rabbit DietHF #5326, PMI Feeds, Inc. The feed is routinely analyzed by the `manufacturer for nutritional components and environmental contaminants. Samplesofthe `waterareperiodically analyzed. There were no known contaminants in the feed or water at levels that could be expected to interfere with or affect the resultsofthe study. Animal Selection Three healthy, acclimated male rabbits, weighing from 2,526 to 2,685 g and approximately 17 weeksofage, were selected at random and identifiedbyanimal number and correspondingeartag. The animals' eyes were examined on the day before test material administration using sodium fluorescein dye procedures. Only those animals with no sign of ocular injury or irritation were used. Justification for Species Selection Historically, the New Zealand White albino rabbit has been the animalofchoice based on its large orbit and nonpigmented iis. _ 9 Gos% 719 -_ 0 ccaawweentoionnst PROCEDURES Preparation of Test Material `The testmaterial was administered as received. to be determined. The. PHofthetest material was not able Treatment Each rabbit received 0.1 mLof the undiluted test material placed into the everted lower lid ofthe right eye, with the left eye servingasthe untreated control. The upper and lower lidsweregently held together for 1 second to prevent lossofmaterial and then released. `The eyesofthe rabbits remained unflushed immediately after treatment. Reason for Route ofAdministration Historically, the ocular route has been the route ofchoice based on the method ofDraize.? Observations The treated eyes were observed for ocular irritation at 1, 24, 48, 72, and 96 hours and Days 7 and 14 after treatment. Irritation was graded and scored according to the Draize technique using a penlight as the sourceofillumination. Sodium fluorescein examinations `were used hours to aid in revealing possible corneal injury at the observations conducted at 24 Animals were weighed before test material administration and at `weekly intervals throughout the study. `Termination At terminationofthe in-life phase, allanimalswere euthanized and discarded. 1 005720 -_-- Statistical Analyses No statisticalanalyseswere required by the protocol. chCwHWe6n1o10n11s51 Location ofRaw Data, Records, and Final Report `The raw data, records, and an original signed copyofthefinal report will be retained in the archivesofCHW in accordance with CHW SOP. RESULTS/DISCUSSION Averageprimaryeye irritation scores arein Table 1, with individual eye irritation scores in Table 2. Sodium fluorescein examinations and the individual body weights are in Tables 3 and 4, respectively. `Thetestmaterial, T-6684, when evaluated for its primary eye iritation potential in rabbits, produced a comeal opacityin one animal, iridal involvemeinnt two animals, and slight to moderate conjunctival iritation in all three animals. Al treated eyes had returned to a `normal appearance by Day 14 after treatment. SIGNATURE Nose WN Stevea M. Gaza Study Director Acute Studies NW = 128-97 Date 1 G05721 -_-- cHCwHWe6n11o01u15s1 REFERENCES 1. "Acute Eye Irritation/Corrosion," Organisation for Economic Cooperation and Development Guidelines for Testingof Chemicals, Section 405 (adopted May 12, 1981). 2. Draize, J. H, "Eye Mucosa," In: Appraisalofthe SafetyofChemiicnFaooldss, Drugs and Cosmetics - Dermal Toxicity, AssociationofFood and Drug Officials of the USS, pp. 49-50 (1959). 605722 2 -_-- caCwHWs6n11o01u15s1 Table 1 Average Primary Eye Irritation Scores Observation Period "Average Score* 1 Hour 123 24 Hour 67 48 Hour 67 72 Hour 53 96 Hour 40 Day 7 07 Day 14 00 * The average primary eye irritation score is the total eye irritation score for all the animals dividedbythe number ofanimals (3) at each observation period. 5 605723 -_-- cacHwWe6n11o01u15s1 Table 2 Individual Eye Irritation Scores C N"NAuunmibmeaerlr A--_AC2 omeaBB TriCs D D CE onjunEctiF vae F__ _ ScSTocoortrael*t 1 Hour F61209 1 1 F61210 0 0 1 2 i2 1 1 180 1 130 F61211 0 0 02 10 60 Mean 123 24 Hours F61209 0 0 F61210 0 F6i2ll 0 0 0 0 2 1 I 80 0 0 2 1 0 2 10 6.0 60 ECEor-- nea A- Degreeofopacity B- Areaofinvolvement Trie s e C - Degreeof ridal imitation Mean 67 Conjunctivae D- Redness E - Chemosis F- Discharge * Totalscore=(AxBx5)+(Cx5)+[(D+E+F)x2]. b Blanching d Purulent discharge. i Injected. t No pain response after test material instillation. u Excessive paving at the treated eye after test material instillation. 605724 14 -_-- cacwHWe6n11o01u15s1 Table 2 (Continued) Individual Eye Irritation Scores Animal NNuummbeerr A--_AC2 omeaBB C Trcis DD E ConjunEctivaF s F__ ScSTcoootrraeel** 48 Hours F61209 0 0 F61210 0 0 0 0 2 2 1 1 10 8.0 60 F61211 0 0 02 10 60 Mean 67 72 Hours F61200 0 F61210 0 0 0 F612 0 0 0 2 01 01 1 1 Is 0 80 40 1 0 40 Mean 53 Cornea A-Degreeofopacity B - Area ofinvolvement Tris C-Degreeofiridal imitation * Total score=(AxBx5)+(Cx5)+[(D+E+F)x2] b Blanching, d Purulent discharge. Conjunctivae D -Redness E - Chemosis F- Discharge 15 Cos 72s -_ cocwHeWns1o10u11s5t1 `Table 2 (Continued) Individual Eye Irritation Scores B N"NAuunmimbmaeelrr AAComeaB Trcis C DDP F ConjunEctivF ae F__ ScSTocoortrael*t 96 Hours F61209 0 0 F61210 0 0 0 0 1 1 10 10 40 40 F61211 0 0 0 1 10 40 Mean 40 Day? F61209 0 0 F61210 0 0 0 1 00 0 0 00 20 00 Fei2ll 0 0 0 0 00 00 Mean 07 Cornea A- Degreeofopacity B - Area ofinvolvement Tris C- Degreeofiridal imitation Conjunctivae D- Redness E- Chemosis F- Discharge * Totalscore=(AxBx5)+(Cx5)+[D+E+F)x2] 605726 16 -_-- cHCwHWen61o10u11s51 `Table 2 (Continued) Individual Eye Irritation Scores "Animal NNuummbeerr AACo2meaBB C TrCics DD E ConjunEctivF ae F SeSTocorotraele* Day 14 F61209 0 0 F61210 0 0 0 0 00 0 0 00 00 00 F621 0 0 0 0 00 00 Mean 00 Cornea A- Degreeofopacity B- Areaofinvolvement Tris C- Degreeof ridal iritation Conjunctivae D- Redness E - Chemosis F- Discharge * Totalscore=(AxBx5)+(Cx5)+[D+E+F)x2]. 00572; - 1" -_-- cHCwHeWn61o10n11s51t Table 3 Sodium Fluorescein Examinations "Animal `Observation Period Number "Preinitiation _24 Hour F61209 NEG NEG F61210 NEG NEG F61211 NEG NEG NEG Negativestain retention. Table 4 Individual Body Weights (g) "Animal Number Sex Initial Day 7 iT] F61200 M 2,685 2,802 2,900 : F61210 M Fol2ll MM 2,526 2.632 2,684 2814 2,796 2.9% 1s 005728 - 0 caww eetnonssi APPENDIX Protocol TP2072 Protocol Amendment No. 1 I" co 5729 -_-- ccawwen11o01u15s1 Sample Submittal Form Thi sform is cing faoAbr eouseSdwohesn soue bpmitringsaempler snfor roeutine ows _GlSHS Enclosewihsarplesand send to: ced re Gasrapnavreystr ROGER C_ Phpesmr OsNtaebSaerrplReSauprstsP_o_ur_ed_:_(9/312p FulGLPCompliaTnXcK.NYee:r__O_FNR1cr5e8) ne EPAFERA--OC1E00R) = MATiE Saroiu; I CT-ec ~e( et TSPpheyosimcaelDaelnscdripttiyoan: tty A orton (occ oratscons fewhpa1rc5e.27Yer SaTonsomDrespomrat:yXsfo ncm oncn o erstag in diu msbbcl ondi. -- ZnYo bySor rH J S3CD-K rE 22X oestmwrspertrs ------ [EC r m--d ----e ----twe By -- ec wrioibme-- sss smopo -- uwneyn AcurtaeOnrael ToxinRa0ts resin ros ekste td 1 ct tons RirveisnGSe5t7cSrreistrekttaarkt isn mtcilC CoF omn iirtve iaarrdeocrnl500 XoOrechrurnioustt sosgpg S TPISo Po hm aa6r-- abe tb hie2piocnnetr syhe-- sm.asona So Cont m t nhey u m a0 s ry pere votaion TT r ism s epeeenoe un Aa =ctDumaTossetyeyrvIn Ra5bbi2ts00g R aoi v I sOeEr CcDo:s ni ti, e s e:miesne Soa t CESoTneyhSo m wong sin -- BITRE Force our BX G--uirnapoigSenE stztonnn mn ss mn ae SER rien PcrocrsnvDt: ___ 122.9 Siovaemses mo se ons soe ma fron) Veco Yooweom--smb | CU5730 2 _-- HAZLETON HSeh BSESOANMSSLLY cowwsenionsst me mine, st paSpuonwshoar:nsata aaron rors Frisy Ee TretaStttuodCyoTriatsleta:onn Study fn ast oneDa1t,e:1m nsPaedirsfeo,rntmiiVnsgscsLaotbnToirsae,toSrdnyoc:.s LabPorofrectaIdetntioficratiyon: Wi Crousy 2 05731 _-- owen w cist ZH0-2E0 Tanker 22 0605732 -_ cwaewnerotuonsst TFhoaense i sPrtimgary Ge Irritation Corraston Study tn Rabbits (OECD Gutdel nes) 2. pTTeoutrlSo5sr5eitsnsg rabbits 3thSeHTrSeTleatievxpeosluerveel ooffafSreesittamtattoenr/iceolrrabastoannepmreoeducSeEdatbine 3. ReLTghauibsolraaSttotorrdyyCvoPrmiapcltiiBacenecCReoengdu1c4t4e1dofnnss/ccSovnduunncdeCuuwrridithestmheesfollowing Goo {[1] CaonduEct 22 + Honregutated stu [] J U{] 1 eso40trcafrtrcat1h6i0uo{s(neh.rEnGSiame8c8h ut fotiticition No! 313" arch 31 to,foodtacboopsseewmyby ROUCALIon bo. 810, October 3, 1588 {opanese Bs) oSd1ie1rirerciptrroeorc,eedttuhreeRsegSiutsndtstihoidnsosesprnoottocoatlhmeeacoreepsinsfiaaornchoyomfdloathtneceSbpewanictehosnytnhmeedeAwenhttaats)s 4 TInQuoedLarpalatirriHteuagycruiAillTseeaTsttnuoe:rndbaenWScaiieusdcdoeintsse,idnbtyh1e4t1ph)eroStQtoaacTnsidli,ayrdsetOsupdaeyrrsacntoesnsodsucStP,ican1id CtehoeolFFiioneanllse 5. lestMaterial A. ICdeentlifiicaatioanreca fom 8. PhTysseicSai)tDeescSripEtioEn form C. ILCdTP eoeThsnteTtceu erHnmbmeteaianrtr nsnaeLatroadtiikniSi oaeotnlnnsa,siubt bseieuS(hlfmo1iioy lencrustclebr)yeieu1sds1mdipiianoydgin,tasusdrsheeio1trsr1sea1)tdie4ton(ene+ti.ftoaSrc,oapnaagmnrdtiitoysintna)aybnid}fosser"ytabboainloaimltyyseseors SHpeonrsore.xeriThneesnetas)amtpelremsin(a1tiotnakefrosr pwioilsFltirbbereqeuessseetnnestnootyhsTeheSponsor 2 605733 - wecwamtosns -Ei bp5%enn E. Ri PeBS sEenrRveESaHmpRlesn eS53 Reoettstrto pTDfB ritidpc iErEpo EmRR Sn ESRRt T SBpEEmB mmes ers . BEL cr SafetyPrecautions we rr 6. Experisental Design A. taimals o0 pPpaYins @ Hra: (NIN) SPF/Hazleton Research Products, Inc. ne (3) AgIenaittiation Hy 4) eai t Ig nith iatt ion FEIEL,Eor (5) MusberandSex 005734 24 - vem 7) Husbandry (a) ih. (6) food BEL ho e A measured amount ofHigh Fiber Rabbit Chow #5326 fBiSifiaenonHwEiSn,E EdRosoee [C] (a EAREmscot and chlorinated hydrocarbons. 14 rt a te AeRn ETtEe Environaental controls for the animal room will be fn G i BE R Te EycnLLETe (8) SeleofcTetsti Anioman ls 9) JustifforiSpceca iestSeilecotinon [ 25 -_-- cHCwHWeu61o10n11s51t RPa0g7e 26 8. DoAdsaeinistration (1) DoAtBhesdefeuoBriaentetards{atailrniawstitlrilaotnibeondoefter1s1iqnueidd{tIefstpomsastiebrltea)l.s, Etahcehpi of mmraaattbeebrriiitaallwilo(lrnotrthetecoewieevlxegche0et.d1e0aqul.i1voqaf)l.eunntdiIolffunt0ee.cd1es1saHaLgruyoi,fd tseosltid solid tteesstt 1mTh1aedteortfeisatltshmewaitrlealrbfbaiblte'svfiilenlyeel.byeTgphrelouanucdpepdeirinnttaoondatTdheouwseterveor1r1tdepsdowdwleiorlw.ler tafoehreonpsroeblve,engtetnhetTloytsseshtoelfedymeattowegirelftalhle.rbefhoIerfldt1heospeetcneosntdanmdbaettfehorerieatlersetlfseaasning ofmfartoemtrhie2"aldeyiesa.tdaanicTnehfesotefeyrepesdproiofnxiatmhaestieGnlrgoyluep10bu1 crrsatabiborifetcssthrwoiyultlIn1 refsmreaocimonend wuIannsfshltouiusltlhaemtdaiyofnobroefaupspterhdeoxitfmefasttceomnlasytied2re4iraehldo.urasppArffotopelrrlioa2wt4ien.ghourIsf, a igsrtpoehucpisTfuiokefedwaabrynnimtahtlaespSwp(oatnthserorere,faorntfhmaeaptlprsr/eogaxrtioemudapt)eeyleywsil3)0ofsbeetcwwooansdoshtehder Ybaefeltgoeicrnintiiynngsotfsilptloharetoixoifnelaowtofeslhytohue4ldatnednsott30mcaatseuerscieoanldi.sn,jurTryhe.espevTcohtleiuvmeerliyga,hntd eayned tofheeTaecfhtaneiymealwilwlillserbveetarseattheed wuintthreattheedfceosnttrmoalt,erial (2) BHceihasostioocnreifcboaarlsleRydo,u"ottnehetohfoecAumdelataihrnoidrsotourftaetDirhaoaisnzeb.een the route of C. QbservoaftAniimoalns (1) oR Tehuelae trreaioa trfreidOtcead utylieaosnrioIfartrn Tialtpaptg raionoxinmiamlastewliyll1, be24,ex4a8m,ineandd f7o2r hours pa7r2fetseheronutrtsr,aetattm7he2enthg.oruoruspI,fwianlodldiitbrierointtaaelrtaiioonnbasteoerfdv.aitnijouInrfsy imirasryiptbraeetsimeoanndte1sai L3tine96pohionutrss terminated. atnhdereat. is7,'no14,irarintdat2i1ond,ayst.he gIrfouapt wainlyl ofbethese orIbeFsceoIrrnvdjaiutnrgiyontishsemsat2yi4l-lhbeouprrreesoqebunseetsrtveaadttib2o1ynsdt,haeyss,Sopdoianudsadoirtf.ilounoaArlfetsecerin may be used to aid in revealing possibie cornea) injury. 05736 2 - cwawesinonss: Trraanes anGtIterdtcrerhiennttiaieqstoutineroenos(fsxAR1i1tot)rhaTecdhbisnestescugnodrtynatd1bode3iri.drte1wcn"Aithd1to1)rstecobvoFeerel bddserbsavuisosgertnnmnl esgaetSstoehietebsSoereatpzLe be i ote chanting to @ foie sess ) BGeefeonrestoepstticmaatpetrefal aduintstration and weekly thereafter 0. BRaaobtybhroSelnviioRaaity1esd gdryoisnsg bn recoded ndRuarcEirnoTggsythsexasmtiundsytiwhoienthannbdeeasa1u)bfswehcietloedc2etsotaines deixipscecraireedeedndtaslwnodhpohad-siteis,ktsa`unSeutrs,viWvHinTg Baentaasvtesd.wiT)ACbLe eSarsimaocnooetnndofhethhee E. StHoa'tSiTsAtCiIcSaHI)EAAmTlSyhsaeiysses are required. 7. pAeTrIt report tncluding those tems 11sted below will be submitted: DPDreeasscccerrdiiipprtteiisoonn ooff tthhe tteesstt pmavteeerntal RDmaiayersSypofetceaxbplseebriisemheronvvtaiatnligontfshneittfIharttriivotnaeteiaonnrdedstoearrttaeid3natsiocnh observation period 8. La1FGfoecra1ctcicaaeghtiepiiirntnileoaatadlnnaioctneeTdfanilotaRtafuah,pdewaitDphataeeiarrrntcgncahdoa,iaptvilhRteeee,sscsroetThrpuhadodcrsryue,tia:dattunn,rgdiiFnwgghiinlonl1sat1e)h5BeRe'eperFSpnoeoIgsrrrTiets1bss1le5emEseennsdattbbeesWtebIoosersetooplyeteode, of hI secording DPorsoteocroelpaarnadtipornotorceoclordasnendacnts ere) Son TBoodesyt SeaTmoeicnsiasntration S Snttoisiccoao rlreEppaatnhgotlnotgsy records. (if ap1icabl.e) Final report (original signed copy) 605737 27 -_ cwcewntoiuonss PThaaens RTohke bfeollAorwcihnigvedsuwpipiohrt1inhg vreocoyrdsdatwai,l be retained at HI bat iti BALAaienttlteegareelrarTaemocatoeyartarptitsnm/pdarecrecTalcrtmoaicarvieteoanHndearhepucomorirsddtsirtty Freeccoorndss nstrisent al forstion snd Svietensnce corcads 05735 28 - OOOO cacawweentoonuiss: TFiro0e7'2s ': FoTocoL peor oShooPncoCrn'seRee2p.re,Bsentia7t0ieve Ly Ed SEavN e ne SeW e A cHaiiltetytoBnPaiMcicssctarsin, Inc. FQHeaupzkrlTdeihttReoynndtKuaWaetsiusicrcnaaonncseintSnSi.ftc.Arlen araore. any ooQuill, 22, 1923 E we S ww wlfz3 G05739 _ 2 _-- cCHHwWe6n11o01n15s1 TPa2g0e72lo Attachaent 1 tame 0 outSeeofdai aren dreae fc reir ee di GSid, t nT ca omT e otE t e TETT Te Sor SIURSf rS ydae E EEye BRETaEha ed @ un "pE a EE . EiSe, ei na dl mtn 0EBRr E toRmRie t mi cot ttt y rw Shae eyeS de EE Se ERI i EE Ih tttere fr th ee the mf at css sees a caren, 1, nd 30 605730 caw ttonst Ko. _Clionsy PROTOCOL AMENDMENTS I Aoendoent No. _|__ I Effective _Noverasa,22,199 | [304 to reflects company nase chats fron HatTotor Wisconsin ioeJRL) in | Modification: co5r30n1inKignbsamzalneBtoounTienvcar,do. w) | | i 9 | (621/01-07-91) -- 605741 31