Document Bvv0eG1xgoMMkw06nDjymdroj

: A226 -- 1323 Giles 1 ggg REPORT ACUTE EYE IRRITATION/CORROSION STUDY WITH T-7809 IN THE RABBIT 2sRon =Es t5=]= 3 NONToOTXOXSPurbosjteacntce36153303322 Paget 1e0 T7000 NOTOX Project 365333 SSTAITEAMENTT OEF GLMP CEOMPNLITANCOE RGLPCOMPLUANCE NOTOX BV. '-Hertogenbosch, The Netherands Twihtehtshieudmyodsetscrerciebnetd eindtihoisnroefport has been correctly reported and was conducted in compliance The OECD PrincilesofGood Laboratory Practice which are essentially in conformity with PUanritte1d60S.tates Environmental Protection Agency (FIFRA). Tite 40 Code of Federal Regulations. PUnaint7edo2States Environmental Protection Agency (TSCA). Tie 40 Code of Federal Regulations United Sates Food and Drug Administration, Tite 21 Code of Federal Regulations Part 56, Japanese Ministry of Agriculur, Forestry and Fisheries. 58 NohSan, Notifications No. 3850, JKiakpyaonkeuseNoM.in85i.stry of Economy, Trade and Industry. Kanpogyo No. 39 Environmental Agency, Japanese Ministry of Health, Labor and Welfare. Ordinance No.21 SDrtsu.dyMSDi.reTcteourn:issen WMa.nIaAgMe,meFnitsing DVM Date: 06 Moy 2003 vate: May 2003 W T7809 NOTOX Project 365333 QQUUALLITTYYAASSSSUURRAANNCCEESSTTAATTEEMMEENNTT ~~ NOTOX B.V., 's-Hertogenbosch, The Netherlands `rTehsiuslrtespaocrctuwraatselayurdeiftleedcbtythethreaNwOdaTtaO.X Quality Assurance Unt to ensure that the methods and TDuhreindgattehseoofn-QsuiatleitiynsApsescutrioannsceprioncsepdeucrtieosnsapapnlidcaabuldeittsoatrheisgtiyvpeenofbesltouwd.y were inspected. ADUADTIETSSOF QAU INSPECTIONS! on-site inspections) 11-14 November 2002 (Process) protocol inspection(s) 23 December 2002 (Study) report audits) 15April2003 (Study) REPORTING DATES A1n4iNmaolveUmnibte)r 2002 (SPF 23 December 2002 15 April 2003 Head of Qualty Assurance: C.J. Mitchell B.Sc. Date: 7-5-03 T7800 NOTOX Project 365333 e SUMMe ARY--_---e-- Acute eye iitation/corrosion study with T-7809 in the rabbit. ``TSh2e69st/uEdEyC,waB.s5,ca"rArciuedteouTtoxbiacsteyd-oEnyethiemigtuaitdioenl"i,nOesEdCeDscrNiob.e4d05in,: "EACcuCteomEmyiessIiitoantiDoinr/eCcotrirvoesion" and US EPA, OPPTS 870.2400, Acute Eye Iitation, EPA 712-C-98-195, August 1996. Sinisntgilleedsianmtpoloensoe feyaepporfoexaicmhatoeflyth5r1eemrgabobfitTs-.7O8b0s89er(vaavtoiolnusmeweorfeapmpardoxeim1a, t2e4l,y408.1amnid) 7w2erhoeurs. after instillation. `InCsotmielaatlioinnjoufrythweatsessteseunbsatsaonpcaecirteysu(tmeadxiinmuefmfegcrtsadoen2t)heancdomepeiat,heliisaladnadmcaognejun(cmtaixvaiem.um 65% Iorfidtihaleicroitmaetaiolna(rgeraa)dedu1r)iwngasthoebosbesrevrevadtdiuorninpgertihoed.observation period. oIbtisteartviaontioofntpheericoodn,junciivae was seen as redness, chemosis and discharge during the. N`aencirmoaslissoofntdhaeysni2c,ta3t3inngdm4e.mIbnraaddnietwioans, noebcsreosrivsedofitnhoeneeyealniidmsawlaosnsdeaeyns i3n aonnde4anainmdalinontwod.ays. 3and4. Since sufficient data were available, the study was terminated after 4 days for ethical reasons BtahasteodcoulnarthceorprroesisoenncheaodfoncceurcrredoobsfytiihnsestielyaetliiodnsoafnTd-/o7r8n0icitnattointghemreambbbritaneeyse,iintawlatshreceo.ncluded animals, Breaqsueidreomnentthsesfeorrdeasunlgtesraonudsascucbosrtdainncgetsoatnhed EprCepcarritaetriioanfsor(CcolausnsciiflicDaitrieocntaivned6l7a/b5el4l8i/nEgEC), T7809 should be labelled as: iskof serious damage to eyes (R 41). : T7809 NOTOX Project 365333 -- PRA EFAC-- Eee------------------ Sponsor 3M Belgium NV. CHaanvaednas1t0r0a5at 11 B8e2l0g7iu0m ZWLNDRECHT Study Monitor 3OrM. AMeSdeiaccaaltdepartment 13-M84CaenntderM,cBuiding 220-2602 Testing Facility NOTOXB.V. 5H2a3m1baDkDen'wse-tHeerrilnogge7nbosch `The Netherlands Study Director Drs. M.S. Teunissen Study Plan SEtnadr:t: 2230 JJaannuuaarryy 22000033 LUTCESITESCUBStTANCE `The sponsor is responsible for al test substance data unless determined by NOTOX. IdCeAntSifNicuamtbioenr BDeastccrihption PuTreisttysubstance storage EStxapbiirlytdyautneder storage conditions. Specific Gravity 3T372830590.93.3 #White crystals AStesroCoamrttfeimcapteeraotfuArnealiynstihse dark 0S1taJbluene 2003 123 Te TEESTT SEUBSTTAC NCE PREAPARRATAe IONN e The test substance was ground to a powder using a mortar and pestle prior to weighing. Ee PRUROPOSSEAANNDDRRAATTIIOONNAALLEE ee c`Tohreropsuiropnopsoetoefnttihailswahceuneaesyiengilneitdaotsioen/ocfotrhreostieosntsstuubdsytwaancsetwoaassspelsascetdheinpotshseicbolnejuinicttaitviaoln sorac Tohfitshestruadbbyistheoyuel.d provide a rational bass for isk assessment in man. r`eTahcetiaobnss.enTcheeofoceuylearpirgoumteentwaatsiosneilnecttheedalbbeicnaoursaebbtihtefatceistitsautebssttahenceevamlauaytiaocnciodfenitnadlulcyecdoemyee into contact with the eyes during manufacture, handling and/or use. - T7809 NOTOX Project 365333 GUIDELINES AagsrreeeqduibryedthbeyAtrthieclDeut1c4h-fAucncttoinonAarnyimaanldEtxhpeerEitmhiecnatlatCioomnm,itthiessetoufdyNpOrTotOoXcol(DwEaCs NreOvTieOwXed9a7-n0d3p1r0)ocaesdurreequsidreedsbcryitbheed iDnutthcish rAecptorotnwAenriemablasEexdpeornimtehnetaftoliloonwi(nFgebgruiudaerlyin1e9s7:). The study DEeutreorpmeiannatCioonmmofunTioxtiyci(tyE,C)a,sCloausntcaimleDnidreecdtibvey6C7o/m5m4i8s/sEiEoCn, DAinrneectxivVe, 9P2a/rt698/,EEMCe,thBo.d5:s "fAorcutthee. `Toxicit-y Eye Imitation". Official Journal of the European Communities No. L 383, 1892 T`OersgtainnigsaotfiCohnefmoircEaclosn,oSmeicctiCoon-o4,peHreaatlitohnEafnfedctDse,vNeol.o4p0m5,en"tAc(uOtEeCEDy)e, OIErCrDiG/utiCdaoerltrioniseisoofnno,r Paris Cedex, 1987. 8Un7i0t.e2d40S0t,atAecsiEenvEiyreonImrerinttatailon.PrOoftfeiccteioonf PArgeevnecntyio(nE,PAP).estHiecaildtehsEafnfdecTtosxTiecsStuGbusitdaelnicneess,(7O1P01P)T, S EPA 712:C-98-195, August 198. ARCHIVING rNeOfeTrOenXceB.sVa.mpwlilel.arNcohidvaeftoarwailtl bleeaswtit1h0dryeaawrnswritahwoduatttah,epsrpotooncsoolr,'srewpioirttteanndcotnessetnstu.bstance TEST SYSTEM Species Number of animals Age and body weight Identification RAlebciongoniRasbebditb,yNientwemZaetailoannadl gWuhiidteel,in(eSsPFa-sQutahleitrye)commended test system Source: (Ce.hga.rlEeCs, ROiEveCrDD)eutschland, Kisslegg, Germany 3 Animals of on sex. `Awneiimgahtlsswuesreodawtitlheianstth1e.0stkgu.dy were at least & weeks old and body Earmark. ANIMAL HUSBANDRY AConcdointtiroonlsl.ed environment was maintained in the room with optimal conditions considered as 3be0i:n7g0a%pparnodxi1m2atheoluyrs15araiicricahlafnlgueosrepsceernhtouirg,htaatnedmp1e2rhaotuurrse dofar2k13perCd,aya. relative humidity of wDehviicahtimoingshtfrhoamvethbeemeanxciamuusmedlebvyelclfeoranrienlgatpivreocheumdiudrietsy i(nwitthhe aromoamx.iBmausmedofo2n0l%a)boorcactourryred historical data these deviations were considered not to have affectad the study Integy. AIncdciovimdmuoaldlaytiinolnabelled cages with perforated floors (Scanbur, Denmark, dimensions l5a6bxo4r4axt3or7y.5cocnmd)i.tiAocncsl.imatisation period was at least 5 days before start of treatment under T7809 NOTOX Project 365333 Diet ASltraonmdianr,d Llaagboer,atGoerrymraanbbyi)tadpipetro(xC.ha1r0l0esg.RipveerrdBarye.eCdeirntgifaicnadteMsaoifnatneanlaynscisewDeiertefeorxaRmabibnietds,and rpertoaviindeedditnwtihcee aNOweTsOk.X archives. In addition, pressedhay (BMI, Helmond, the Netherlands) was Water FNrOeTeOaXccaerscshitvoest.ap-water. Cerificatesof quarterly analysiswere examined and retained in the ImTReEpATTMMEENNTT Aanhiemaalltsh wienrspeecintiaongowoadsspteartefoorfmheedaltphr.iorStpoeccioalmmaettnecnteimoen nwtasofptariedattometnhte, etyoees,nswuhriecthhwatertehefree from any abnormality. Btharseeedanoinmatlhse.reEsauclthsaonfitmhaelswkainsitirteaattieodnbsytuidnsyti(lnaotiiorniotaft5i1on.3nomtegd)(,5t0h.e5 -st5u2d.y2wmasgsotfat)rhteedtweistth gseunbtsltyapnucleli(nag vtohelulmoeweorfladpparwoaxyimfartoemlyt0h.e1eymeib)aliln.thTehceonlijdusncwteirvealtshaenc goefnotnlyehoefltdhteoegyetehserafftoerr sabeoruvtedoansetsheecroenfderteonpcreecvoennttrool,ssofthe test substance. The other eye remained untreated and 7I.m0m)ewdiaasteilnsytialflteedritnhtoe b2o4t-hhoeuyresobosferevaacthioann,iamasloltuotqiuoannoifit2at%ivfelluyodreestceerimnininewcaotrenrea(ladejpuisthteeldiatlo pH dbraimgahtgeg.reWenhestnaicnoendsiadreera,edinndeicceastisnagrye,pitthheislipalrodcaemdaugree,wawsasreepsetaitmeadtetdo aasssaepsesrrceecnotveargye.ofAntyh.e total corneal area, OBSERVATIONS MortaltyNViabilty Toxicity Body Weight Necropsy Iriation Twice dally. Atleast once daily. Day of treatment (prio to instilation) and at termination. Niaotinoenc/rcooprsryowsiaosnpoefrtfhoermeeyde.on animals sacrificed for severe. `aTnhede7y2eshouofrseaafctherannsitmiallatwieornoefetxhaemitensetdsuabpsptraonxciem.atTehley 1i,ri2t4a,ti4on8 scores and a description of all other (local) effects were recorded. `Tohbeserirviattaitoino,n twhaeshiagshseesstssecdoraecscogridvienng twoetrheerfeoclolrodweidn:g numerical scoring system.At each N`CGoOpuaRlcNicyEe:rAadLtoIenRoRcoIoTfprAdaeTcneItsOyiNetya(yarieanmclousdetdseinghsteGutlaikoegnfo readinP)OISE)... `NESecacarsteytorduessdcoaarrremaGi.flineuosredaaerntesaailscsoeonfftoiapsraaic,ye,d.idaelsailzosefooffips Sichlbehaareolybsdcusrceda.m.v.iisse.......m.--....a3 (Opacuecomes, nsnoldscamibieBrcugh he opachy eer" a : T-7809 NNOTOXProject 365333 EfSr r oInEsr VE wSs HERRI C f R amE y e iiBRe AaE TT ce omer mos S E Sn EiE R meeE Fe te te oc ri SS ERREE RSRRATE S B S RS ttm tR ER EsrtcsE oR emesrtrA omans T pE P F tr e NcT ErEnSE enrTtnI Eanesrsesc, hosrseR srne oenseCrnom anrssoereTeATIOn FST rrceraelessarkneiedayandnernagimoaonfnHsCoE Dura--iSnoep--sS--EbEsSSeoaroueneors m evrCaottoso scoiLfobm,eo hveimcoiannrc isimuo m vo l app v erteuri nw eo(onmn ai esc eooaf1yw e 0,aSes odsa Io T7809 NOTOX Project 365333 RESULTS IInrsrtiitlaattiioonnaonfdapcporrorxoismiaotnel(yTa5b1lme g1)of the test substance (a volume of approximately 0.1 mi) into one eye Comeal of each of injury was three seen arsabobpitascirteysu(lmtaedxiinmuefmfegcrtasdoen2t)haencdorenpeitah,eliiiasl adnadmacogneju(nmctaixviam.um 65% of the Iridial corneal iitation a(rgeraa)dedu1r)iwnag sthoebosbesrevrevdatdiuorninpegritohde. observation period. oIbtsteatrivoantioofnthpeericoodn,junciivae was seen as redness, chemosis and discharge during the. Naneicmraolssisoonf tdhaeysni2c,ta3tianngdm4e. mIbnraaddnietiwona,snoebcrsoesrivseodfitnhoeneeyealniidmsawlaosnsdeaeyns i3n aonnde 4anainmdalinotnwdoays 3and4. Since sufficient data were available, the study was terminated after 4 days for ethical reasons. Colouration / Remnants No staining of (peri) ocular tissues by the test substance was observed. TNooxsiycimtpy/toMmosrotaflistyystemic toxicity were observed in the animals during the test period and no mortality occurred. CONCLUSION tBhaasteodcuolnartchoerprroesisoenncheadofonceccurrorseids of by tinhsetielyaetliiodnos fanTd-/7o8r0n8icitnattointghemerambbbritaenyees,initawllatshrceoencluded animals. Breaqsueidreomnentthsesfeorrdesaunlgtesraonuds according to substances the and EprCepcarritaetriioanfsor(CcolausnsciiflicDaitrieocntaivned labelling 67/548/EEC), T- 7809 should be labelled as: riskof serious damage to eyes(R41). n : T7800 NOTOX Project 365333 TABL1E: INDIVIDUAL EYE IRRITATION SCORES --- Comma ins Conionciuas TGiomieantger Opacty Asa aFrlueoar(4) Redness Chemosis Discharge Comments e Noses e-------------------- 24 nhoouurs 7ho2uhs 2123 es 2233s 11 11 23 ` 33 :i F2E . 2 zs s _S--Nosor 21 nhoouurs T48ahonuars 1 2 23 es 2233s 11 1i 33 4` 33 bi 2"ERa 2FE) anos --_--_-- 21 hhoouurrs 8 hos 2122 FE ow 11 1 323 b4 pl 222 83 _T--2nes FE 1 33 FI Fluor area (4): reen staining (percanotfagael comeal ares) alr fuorascsin veatment. 5ACTommentGGsrr:yoiyvhhiitteediGssccoolloouurraattiioonnooff hheeecytatiadtsn(gsgmneomfbreacnraos(s9)0ofnecrosis) FE Reduced siashoty of th ayeide. `TABLE 2: MEAN VALUE EYE IRRITATION SCORES rims Comes Moann2s 72 nous Cononcivas opscty Redness Chomesis 5 o 2 2 1 1 3 3 0 py 0 2 1 3 37 #Anima specications: Aamaie eSepe Agese tsan ------Be ody weia ghts(grm ams) g-- (weeks) z ns tr to apptcation 2537 at trminaton 2552 s9%o 2 2: wn3s s a22w37488e 2041 a2m10 12