Document byNNgy5GNGqaK19a2MRBLeRJO
#BDE)SHTAEGZELYETOSN TeEcoWnADaIvONenWcIaSCnOeNSIN
S70
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Division
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EEE oN
FINAL REPORT
{ MAY 01025 4
WIHXrLIeCSeOoLrDO.aGYZMIISNMEIIRNEVGRIMCAE&NSMANUFACTURING COMPANY YleaiL, MN 55101
C HeY a SAMPLE NUMBER: 50202473 SAMPLE ENTERED: 02/15/85 REPORT PRINTED: 05/07/85
wPLE: T-3727 [RCHASE ORDER NUMBER: T357842, REL. #505
ENCLOSED:
AE RCUTv w E ORABDLvEtRMTAOILXRIRCIIITRTARYTIIT-OANTMIEO-TNHMO-EDT,HMOEDST,HUOMDMS,AURMYMS,AURMYMPAARTYHOLOGY GRAAUL RDEAPTOARTAPPENDIX
SSATTCUEUDVTYEENDT1IO.RXEIBCCLTOAOLZROAGY
&Y AND FOR HAZLETON LABORATORIES Re DATA FOR THIS STUDY ARE KEPT
AMERICA, INC. ON FILE AT HAZLETON
LABORATORIES
AMERICA, INC., MADISON, WISCONSIN.
01100
Se
@THSATALKIZLNGMLSANVEBLOTVD,IO- 2NN. BOowReTorono+mmNeAsDoEsmRen,nccWIaeSnCnOcs.NSIN E5757 PCChhReemm0iiO0ccaa2l4l1N&&4B7iB1iooMMeeTddiXicc0aa3ll8S5Sc8coiAneEnccReesAsDWDiivSviiss0ii5oonn
PLE NUMBER: 50202473 weLe: T3727
Pace 2
C0 ORAL SCREEN UsJjersotriivael: LeToSudneitpeiremtinaertstheBOsootuet)s. Boroarlde.totrkivtTotrytpsreordturceeidrywhecan, hetest
OTregaarinnigsatCihoannicoaflsE,conSoemcitcionCoo40p1e,ratAioounteaOnrdalDeTvoexliocpimteyn,t'sadoGputieddeliMnaeys 12f,or 1981. TosSPthtyusnMiiacltaeilrtiyaDloesfscrTioTpo-tt3i7o2Mn7a:teriOaFlfs-uhiStpeenswearxyhessolipdurity and stability
Getorminat ions on'F ile. Tes[5t wReaenikismgaloa:f agYeodungof adtuhleRtrSpmralaegugreaa-nDdaT wfleemyalssr traalibnint owerreatspro(cauiprdperbdlo:xBiammgaaiitonentltayiionee!d in
doenttilnuamsatiaocncespserttoadcoammearcifaalvelaboararteo.ry reed and cater, and meld for Gfecrcslinhaotuesdedabnyimaslexs wienregrocuhpossenof atfivreanadnodm fiodrentthieissdtudbyy. aniTmeaslt nsunmibmearls aa Tnhdroucgohroruetspotnhedinsgtudeya,r teaxgc.ept FEofooedr aanndovwaetrenrighweereperaiwoedilajbulses abadefralrisebit.um
Reafseonsfeort1STpeecinesrSoealresctwionet TeTihettrrataias tLhoenganiomaalrsclaorssiDceaslelryouusseddadtues. to
MetaThreoved:e1u7tm0`dF.i2veL0o,nmaal5e7c5h0a,ndS2fe-ia0v0ye:afnPedemea5ll.se00 raaTtsesk)Su:eseidgyhincgonebiesteuessenof200fouarnddo29e8ets
PreaTp0uaa%nriaftToiorotmnetisannuddspewAendnsmiionmniivsetafdratawiiotsnhpecwoifarfniTeedsotilcMoaantncsernitParalavitiieodnF.otrv
usoacuhrtedrosebotlheve1al', ftehre Each suspension wes
GS2ea1vciahogueea.animTaoTlheosboda]esseedBFvUioparlenum0eiteod.fopFieanasgci:had tbAesnotdyimniwdxeitioguihrgteee)uaensddosu1em.0s.0wesnmdimsisknogilsvteofelrsetbedoddybyfor
Seven
co1101
HPAHZALEETTOONN oem meve CohmacmaSSttcaidntssiinnesciOivni
and twice daily for mortality.
01102
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PLE NrsERs 50202473 mies T3720
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SSTeeatsotercaaftmmiinna"elHssariBenAolcbSoiptnrloaogduReastsDResI-ieESyp,raogHtusssi-DeeennualaoyFbs s1t/r0ai5n
Temperature and Humidity of Animal Room: 221 1to 2B5 DeRgreeIs C.;mii
Mveehtihcelde":et Cfoarmnini0a1t1rationt Oral Gevege
Date Test Started: 03/01/85
Gate Test Complateds 04/09/05
Eatinated Oral LOSOn: TSNaaNlmaiCaa-nts0.d20e80ntage/kagCnigonftoaFboBodtaydy5we1ie8gih"gthet 0.51 akg
EH
RA
Mortality Sumary (Humber of Deaths)
GDpoaslaetge HTouErs a 2 L3" DE aye soEE sae EE aTotal
020 0 00 oo 00 00 00 oo 10 1305 10
SZ0.oo5o0 000 so0 3g0s033313p0 Ir1l0IcI1I1Ci20I02iR0Di0 ioT2 zZ2Iom 5/m5 m3l/5ann8/a10
DostaogneesLevel InAeiveelrage Bo5day l5isighhtesrm(5i)t
rele 280.:%230
m m we 2 w2 =fsda
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m B2es 2ais 2222400
50
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*nTahtaiknugr,L0A.50K.s,id anTdea W.sonLt. eFnazcieo., Li1m98i1t.s uaAinceompeutseergiFpireodgrSamerfeorneesti- } 35a Reed-Muench cumulant method. Drug and Chemical Toxicology 4 (3) C01i03
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FouP rs E onye E
Dosage Level - 0.20 grkg
Hotes
SSmapamA preesereaasdbrnoorumna-lstaS3insod3anraly5 o9s0 s0ssr0 0t0 iaso s0 i0 r4 e0e0
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Sp -- Clinical
10"Hoursee
DosageLevel - 0.20 g/kg
FSdoprppeeensereieindvintoyrmal S53 0505
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0 0
RVosoedntilisaTlthteetanroaeds TsbSom"ans 0
adeppmeicrtiaa'ltsn abdomFi0nEal 0 9
PoleeurieacrttaoinsTMchar6e8 80 50
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Fenaies z 51I1303A 03a 40 040833Ib 00404sHaT0 45os4bosdb 4os40s4 4433 33a0 a 0 8 bob 8 s222220 0 000000 111222 01 000000 11111100 0 00000 P8 S53ii Pii aoiLbi OoLb Oc Los OL R3 Rob
C01105
HAZLETON vorronenscare
Chemical & BioMedica Scions Division
PLE NBER: 50202473
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Firnssns Signe vosrtimed?
10 oursa 12s as S oaye e womos wnow
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MSRSyeeoapremenaeeaairreaidsvintoyrmel 43ST0l833 f445 Commision 8 4 4
S0fs2as8 7ai0 3ia02zs03zs80za02iao0znp0oozpsoonz00soo0oapnoo0 ezn 84S EEEizozozozoz
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milRareyniios 5 05 08 Ssoon0eSSoYoIoInZoOZI2 O2lo1 Zo2 la
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SRilGAmisTheeSrie ceesd0 E053A058E30 JE3E0 LeEA3E1 AE2i1 iE3EEA1Eo10o1 0olzao1ge5g1de0
"animal died in p.m.
01106
@ HAZLETON oreo amcane Chemical &Boa Sciences Dtsion
PLE Nurse: 50202473
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Stintant Signe tentinents
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De Sorspeaeagerreaew Ldtevreelna-l 2.30330 0g/7k33g b32 Pt Beiiatcesie izzii iicz: :ii: RPapass int elC e E oulgenital area S 0 0S0 F 2 0 - i - - - z - - - z - - : - tfBraongiargaewet 33 0328 03fF8 Y3BsEFIFiecmailresIiiIaiiiaiiwo:ziocn:z:owizcooimocc: e eEeentr niredSSSooOsS b0I p E#dSS3IIIIS IIiIiziiIziizI iozozooziziooz: iiooiziioo:cc oTeliheoye anSSommUannaaSnaeYs' Sit eamia o eo. s . -
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$0 d1 22 3S: 1 0 = = = = = = = = = = = =
*Two animals died in p.m.
01107
HAZLETON worms sncne Chemical Boats scioncesOviion 507KINSMANBLVD. + .0.BOK145+ MADISON,WISCONSINS767+ PRONE (508 20 4471 +TIX 098RAZRALWES0 01108
HAZLETON women ence Chom & Baad sciences Onan
PLE Neer: so202473 NT
Pee 10
co ovaL screen PATHOLOSY Ceont nus conten
Gosage Level: 0.50 5/kg of body aight Date Dosed: 03/12/85
GWanatsarall seSox OtoeTwpoBseetcrnbiafyices FrNeeeracisro.otpusstytaarrCstoemdmeernaitnnsansarli,uamnd Cpaairinneest.
Smo
ams om 2 -
BStoenosonn -amueltnipsle,odonriabnrau,n efoccik, ouPp
ams ons
SGrahraakutnreesdrtpasanrdiopecerruiloatnraumndeiscoh2rarga%eed,ar
SpSiereiramlns,PTeeraeeritite hhnaemualtiplmmy,edmsetn,y
cosas na -
SStomEach - mreiesed,etamn aeversr, upButtoe,
ams om
re Paariinnao unnpaarrimoanaalaeaurSesrestaaBinteemd apar
Snm SenpaEtirnRdE aiieyrralmruygshmeaansea]s miStnaeaorrietm]euti,nsniteoesmtsiinnegg. -
as fou -
PTStoEmAachhAn,- Radariabraaun armes,lupUa Stoen
cssse faa
Bn neater Putian No visible 1esions.
TE
bBroounlpoarinerselesnteien; Sstuomach <
EE cess fu
Ne visible 1esions.
eninal thin stomach = multiple
oVnioealrl 2 lsobeesse:mmudoe
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ent 1
to1109
@THOARZNLEBLTT.ONSoaoRmOsRcmcSnEnEeRA ST oChenmic2ae& BioMeT dical a Sciencee s Division
PLE NurBER: 50202473
[_--
eis T3720
co ove screen
cconTinueo
PATHOLOGY Coont inusd)
Dosage Levels 2.00 5/kg of body usisht Date Domed: 03/06/85
Namiinneer Sex DiskTBesiteriofaiyceds Necropsy Comments
are m1.
SSIatnnoRmeaadcrthainnai-le=cnonTtmiaalitenessriennlio]irnmaalmTeotnf]toyoedl atnowd,
mesa Senieletel
aes m1 -
SSrtoenodmtaocrihannes-le=cronHtmaaeitneersieSntoi]rnnaalmTetef]oeod tsonwd,
meaia Seni luta:
ae nz -
TpSatatodtmearcTnhvse~rglanedcuelmatruemtiesdesSodmifafnusely
ass ow 2.
Liver = acoantuated lobular pattern.
asm om 2
No visible lesions.
cases Fa -
Spirtneogtmaadcihin~
contains =" TTios
nwoirnmaeltatnfoaodnd acnldase,
mcaia somite:
caer
1-
No visible lesions.
cases rz -
No visible lesions.
cases Fo 2
Liver - accentuated lobular potter.
ENI
Liver = accentuated lobular pattern.
013i0
@HHAAZRZLOLEE7TT.OO7N.N55v%weonromRmssAwsOoonnWccunEneeE ncChhaunmaiiecast &SBioMe+ aF sdtuaaSSe icinoenss Gvhiissioonn
#015 rane: S092
vee 12
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Govan Loalt 5.00 orig of Sot TfaEmaD se oilveBgiTTiryces cowses m1 we mw 1 coe m1 ams ow 2 coos mz ses 1 -
ceonTvagy
weight Dete Deed GIULAS eoropey Comments I-- Roriaom = atainet sro Parineun = stained brown. -- E RFairnifsmr saupfan=dr gtiaiegtedeSrrgss ups Tod CtS earra O IPRIa -- RheereA
osm 28501 Frz1
-- B JA eter ietosy Perineum - stained brown.
owes rz -
bJ ibsth i--
wm rz -
A Fariman =L gtaimes Srauns vas
eHo EireartIiioe Aee of tahaebainimaa lraomeTraigedBSToeromandrEfF roeA teePesrleetrererer
rani Ta Ie ete Cora awrET ey,
v 12, 1981
01111
HASZTLRE.TO0N,5v8or5onR e eA WnScSeR Chemica & BioMedicn al Scie ences DDivinsion
PLE mar: S020247 area: vss
voce 13
------
ObSSjSieooScCratornirotvaneiti:nongnes 9tT%eoForadtheteTteoesorSttmrigunasgenu.ibsSsthscheeaeminiocroneealtooasFnt,ivEYeCoaoovnmltieirvntaetsloCoamdofeeorrpProsiieonmmliaaicrroeyyncloSsuehkdniiednndDceirovirenrilrdtioiatpttairtioiaononsnntsss
Sie Laareating Sonica
TosPBtrveSMiaetnetrainadBlessS cri1n3iL 7i2in7: eOFrfe-unhtitehawa1xy 0solid Sour.
suabitity determinations
TePSsRtreoowrvAeinTnaianmtndattla:insedonntYUnoitiuneaendgsgeessSatdeumIanle.itns'roernSmaombrebteneietbspaerre(astasiaprdpeordroysxioRnmoaaittnnaeillsyyni1n1dei4diweneaedrkiossulotoedffkduaeaglqgsleeuy))ariotonffertsh,e
Ted Fo nas Teen, parsing aber tery Rabbit
Thras scclinated fomale sninals, weighing from 2040 te 112 3 vere
SFSSohioaEmararaRloxssiTtnewiIasoreneLl"ypaTSrassteaoetnmiityafsireesomsuerosyhhteobremiaidteeo'nbFaorrmanuiseepraesrtoonndad, cTmoaoritrnietosanpiponeneddridinuogrdi:enaTegrstttheeg.
ReHTsseoanTnaeforrabSutpiesciheehassbSebaeelaanncttithohnataniHmiasltoraicialmly,, thteheNNeewZoZetlaenrd nueneite
Proparation of Tast Hetorialt The sample was dosed os received.
TrSTeThateEt"hRmetTnartam:nIetnnedTththeeaapreestaeeasintandsemoatuoSereorrvio0aer0rle3opdpou'asmsdsatrhmaipt3ophli3ieTSesudraitmtpngo TlstgehheaeInoiinent0teaa0ccttEdHskisikneni,n0o;oef9f%saeaelcSiheeendn
Re Tost on matn postinivyressing. Collaruse
C01112
HAZLETON ome enenne Chem&Biocdaiel scfonces Osan
01413
HAZLETON wooo encnne Chem&SiocMaa l cinces Otsion
co 5501 KINGMAN SLVD. 1.0.BOKTo + MADISON,WISCONSIN6707 <PHONE6527471 +TX 5sFAS Wotam
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@HAZLETON veone emcee Che&BmiMeidicaScaincles vision
01115
EI HE AZLETON womens momcnne F Chamica BloMss dicalSa cincesl Oivision
veLE NurBER: 50202473 vee: T3727
pce 13
0 eve iemiTaTION ObGj22euociS2tdiaienrvlgdeiil:nneegsx1TpSofoosrdtshoreTteaasrOtmorifinnggeaanCtthehieaetmziiolacnma"auvlepFslsa,traonSEfceoecaatnciouvonleniacron4s0Ci5or,syrpieaatrcauaettttieioonssiEvbpeiarnnoegdiubrcceoeaidniseatfieios)olmnmlseonwtin'sg Corrosion, adopted Moy 13 i581: TesFPthryisHeiasctaelrainadDlasSsctrsi1n-TtL3ii7atn2DEt SOoFafn-Hauiohri.tehaswapxuyristoylidond stability determinations TescBNtooantwttaionZnniaunaoalcluaaisngdesseYUconiauinsnveeg"teSamtdotpuerlraTteiotnkuirreatadab.rbeiLtasbshpaarro(asnatuuperprmeyrid,osaxiRiatmmbeaobitoonesttloayniDint1ee4rttdeouldea1snndkadsuussiteodscfueoecnasi)g.ie)yshpiaoTnfnebiastotohnserseens Far an accliniaont period of at tases'? deve. d2cTy4hheormheeorsnuo'rcsascatellpiirrrniaeoansrtd.oodmto"ffooetnremlsaytltethehmoaastnteaiersmitaa.slnlsi,maaTlhdwsemeiinwgaiinhtsiihmtnaeglsnstef.irosoniemavnes2si6on6fg6w.eorteeSouoio3de0xin0eo0nii9Fnn,ldludawocyerirseeashseiinn ornidtCaariroenmpaanrdsingaceaa,r taega:t animals vars dent ticd by animal muster ReaisnonalfororSCpehcaioess bSeeslsadctiuopno:n 1Ts"he LNaensweZserabliarndanUdninteensilgbmiennetersabbeiits!is the PrG2 Geoipsnasaralttofiy1on0d.Ge0toa5fesrt3mTiesneta"nBteiMaouatnetsiesruLoibeaaesnld":msatudhraaThedrtoeornssdaismetepttylehermdieauntsneasimramtdliho.nesaetdveisaisno,n raenscaesiiivnevedai.ieeinasce]obfulk TrceFFaoeatnantmternaamtlar:atsteerrisEaeoallncehCp1 ylroaahcbebsedieatrsonitrnaeggctuehteaisnv'eesrdvteharf0io.rn0wd9natnrgala.osw(tss0:ee.dc1o1nsmdglonctouroFsoilgporrhneteveToneoptq.aeuriuvIopawbplisete.rhnto)fstnhgemoeftleotrvhieearl ond than released. Tha syaa af the rabbit remained ont lboned,
(01116
@
HAZLETON 3501 KINSMAN BLVD. + 7.0.
"eowones svencanc 80X 7545 + MADISON, WISCONSIN
5377
+
Chemical & BioMedical Sciences PHONE 608 301-471 + TLX 703938 RAZRAL
Division Fos U3
IMPLE NUMBER: 50202473 PLE: T-3727
PAGE 18
CO EYE IRRITATION
(CONTINUED)
Obss1,oerdvi2a4u,tmio4Fn8l,su:or72esTchaeenidnt9r6ewaastheoudurssesdyeasftotewresirdetreoianbtsmererenvvtee.dalifnAogtr
otcheula7r2-hiorurritaretaidoinnga,t pessible corneal injury.
Irritation wes graded and scored according to the Draize technique.
Animals were weighed just prior to test material administration.
Patdhioslcoagryd:ed. At study termination all animals wers euthanatized and
*DarndaizCeo,smeJt.iHc.s, -"ADpeprrmaailsalToxoifcitthye."SafAestsyocoifatCihoenmicofalsFooidn of the U.S., Topeka, Kansas, pp. 49-51 (1959).
FanododsD,rugDruOgfsf,icials
G01317
HAZLETON voor nce Chamicl & Scant cance vision
A ------ wees Tos
race 19
0 eve inimarion
continues
SSTeosntoomrinnahla:t
RfAOolRnbiSnRESo,
-- IraRba bAit,sf- Neew ZasTetsatenrds
utnniittee
TTeesmtperMaatteurriealasnd THu3m7i2d2ity of final Room: 19 t8a 2B 2 egrI ess C1ares
bate Test Started: 02/2008 Bate Tost Completes 03/4788
PRIMRY VE iARITATION scorese
ossesunrion peRioo
3 WRahpbbniitneHoan
23553 ftooouuuurrrrsss,::
273F3H3
72 oun:
BH
L The Prn imaErYy mESuinnLaLleriEtatison sScoretdisithme totsaelmaveLirriStSatiieon score
CoTmoeTnTtest:ingNoSlptainTIrTasIaEnsSs S(wEeTsTslLiEzation) ues alicited from any aninel No cornaal irritation ues sbasrved during the studs.
C01i18
HATZRLOEBTL.O7N.08oErWoRsemRcnneA TEChemi ical &Bodie scirocnoss oDsoonn
ws rove: Tosaers ee 132
I
55 Sve RTT
coninueD)
Individual EvaTobiiaet t1ation scores
ANniamaml ObCseRrIveTtion CSoTrnRs SSciomree Iarieis fScyore GCoimejputnciteinvses sSecoerre s
Fes aBalameeesr Glee
800800 050 8 0b 4
1F+1F1szo oPa o1irr 1 or1
ooed
wns op of Formie sitemeers 05 03 05
bs hn o8o% 4boada1
oz
GSwhouesod55208 85Sror oSs dso3gssovo oz
FO7815 GSEdt1iwemHetoeursersoob88050855o0b
48 50 0[]84%d%0 oor
d3so1n oss o1dgnooo0 o4op
Sodium FluoraTaambssie2Examination
Wnaimnsal preGmepiareentrton PPagyidne
frFoeoreeelts
n=eese
eneess
KFEoS =RNo L stain Lreotenntiuonntion caren of comme involvnd).
1. OF rganie sationChfoermiEccoan.omihcee Ccoooonperaastionenatnsd DSoetvellopmoentmi'sarGGuuieiddeelnliinnteess 2. EOoarrdaaoIipztEeseTdam3eM.ta4iyS.ede12r",aPapRp1rn9Ia8e1ia.saaalrSof haths5elSSaSafnaeetpyaooffChCeihmoeinmcioafclaslFsioonindeFFnoodondsdl,su,gOor0urfg1ue4sg1s9,
:
PAGE 21
to
QUALITY ASSURANCE STATEMENT
Study Yo. 50202473
The report as herein attached for the above-mentioned study has been reviewed
bIyn tahcecoarsdsaingcneewditQuhaltihteyGoAosdsurLaanbcoeratUonirty PofracHtaizcleetoRneguLlabaotriaotnosrisee.sseArmerfiocrat,h Ionrc.
the conduct of the study and chat the reported data accurately reflect the 21 CFR 58.35
describe the
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Date of mspection Type of Inspection Acute Ocal Toxicity Study in fats
a
2/25-26/85
3/26/85
5/01/85
Process Audit
Process Audit Report Review
Primacy Dermal Irritation Study in Rabbits
Date Issued to Management
2/26/85
3/26/85 5/01/85
2/25-26/85
Process Audit
5/01/85
Report Review
Primary Bye Irritation Study in Rabbits
2325-20085
5/01/85
Process Audie
Report Review
2/26/85 5/01/85
2/26/95
5/01/85
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(1) Teyehens and Eachar Torsacion
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"
01167
Inicial Sodium Fluorescein Exam and Animal Body Weights
|
i
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I-3222
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S02029Y23
prmeste NO
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Date Antaals Received _2:-5-8S"
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Reviewed 37 pon pate athe
source:tazletan Research Decducts
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01168
.
Primary Eye Irritation Test Observations
|
SR pmnEGRL, --C N4rwccmonsA723727 wwe 30202923 1
Tose relat
Group OA
=
opszxvaTion Prato: ) how
= OOOO
i
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: PTT
4 = Perviens Disehares
. blu, 8 = Clear Discharge
b = Blanchiag
:
IM am = Injected
20S = Positive
cormart Tpiebelial Dmage, Testis 17 0= Som Corneal inn Tpithelial ml Demage, Heh Piling o1l== Eran Pazmus Corneal Neovascularizatica
.a
Reviewed By:
SO Date: 3oM-3S Eye Irricacios Score: 23 te
Od
ud
.
-
.
.
01169
Prisary Bye Irritation Test Observations
|
t=us Compound. 17-3727
re. S0202Y23
Test Eye Riaket
Gran
MA
MB snes NA os ot i 3 vmvasnad
WET
2A Ter AH Teens
Ee LT Ek IOIO)]
orm LLlo IN| .
x
To [0lo IN [|
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7 == CCoorrnneeaall EIppiitthheelliiaall DDaammaaggee,, PPieleilnigng
21a3CD) === BPINelentagjinaetctcehitvieHendegmorrhage >
GE
====
CCPoooarrrcnmmaesupaaellp
Epithelial Demage,
Niceaonvimesealarization
Pitting
208 = Positive
-
, ge
Reviewed 37:
sua vaca: 385 tre tevteasion score: Spe
i
:
.
C0170
i
r"4ere CompoundR T= 3727 Tee tre Riek
ve. $0202973 | Group A
MB ested MASeconTidsfolhle ovicngitasciwiltacvioan dof vcaiste -- Uonaated
opseavaTion peRzon: 48 how
== x OOOO .
Tolo Io [NT 1
:
TTT
T ee Loe lo 1p [ y NN]
A = Purulest Discharge
> BC5 === CFblaeetnaicrtheiDniSsgecmhcarrrgheage W2I0SM8 == IPNoangsjaieccciitvveeed
Revieved By: __
ai
.
Orb evr 3283 corneal Tpichelial Damage, Peeling
:
7
1
===
CCFooarronomesseall
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iy
So Date: AES Pye Irritatics Score: Zen
i so
i
OLi7T1
Primary Eye Irritation Test Observations
|
ME ed to ripint | rest Compound 7-372
Tc re Riot
NA al of
-- mw. J0202923
Group MA
NB for
seconds
opseavATIoN prio7n2h:ow
eJrOOIOQOIO)]
orm LLL IN.I Che -- | ml,; Ta N 3 T Gets [0 10 [0[| N |
hoi | 9 Tid Toot TTTN
bee += repno:mts(cFcs . B= Clear Discharge dina, D = Blanching
IW = Injected
wii POS = Positive
195
>
196[ + comet1 pttTee,Nei = Corneal Epithelial Damage, Piling 11m hit Sm HL 8 = Panous ET 1 = Corneal Neovascularization
. Reviewed By:
Ss!> Date: INS < ye Irritation Scoorrne: 23 Hmal
'.
-
01372
Prisary Eye Irritation Test Observations
Qoescmmn T3727 ww 50200923
re tm _Righer
cry MOA
AOR vues SOB EsceEnttotetolvogrfsisitsionntonaof ctr | _o_ toasbad
oasERVATION PERIOD: 70 NOU
Ee =oe eJOO Q )
Chm
ToToTo TINT1
orm Toll. IN]
A = Purulent Discharge
= Corneal Epithelial Damage, Peeling
.
3 Clear Discharge
CD == PBeltaintcehinHgemorrhage
-
-- h7 pi eed a see 202522 Sttnnysrvetnnsion srw Sa 1M = Injected
2 = Paoous , = Corneal Epithelial Damage, Piling
G = Corneal Epithelial Demage, Pitting
1 = Corneal Neovascularization
A
.
.
.
01473
@ HAZLETONLABORATORIES AMERICA, INC. 001 KINGMAN BLVD. + PIO. BOX7545 + MADISONW,I50707 + (608)241471 + TLX700956 HAZRAL MDS UD
February 25, 1985
Dallas D. Zimerman, PED
Manager, Toxicology Services International
3SeM. CPeanutlerMN 55164
Dear Dallas
o
i FEBZ
3
5, oy th ei
EEE
Esanmcplloese1d-3p7l2e7a,seHLfAindNo.tuo502c0o2p4i7e3s: each of the following protocols for
Protocol No. Study
| . e2-220029 T2071
APcruitmearOyraElyeToIxrirciittaytioSntudSytudiyn RiantsRabbits Primary Dermal Irritation Study in Rabbits
TghueisdeelisnteusdieasndwiGlLlP breegucloantdiuocntse.d in accordance with the OECD testing
Potlheearsse stoigmne.allWecopciaens,inriettiaaitne otnheesesetstufdoiresyouurponfilyeo,uravnedrbraelturn the authorization.
Should you have any questions, please feel free to call.
Sincerely
SSttuedvyenDMi.reGctloarza Acute Toxicology SEHnGc/lmovshures
Chemical & BioMedical Sciences Division
Co1174
@ HAZLETON LABORATORIES AMERICA, ING. OT KINSHAN BLVD. + PIO. BOXT545 + MADISON,WISI707 + (608)2414471 + TLX700056 HAZRAL MDS UD
PROTOCOL T2207
JUTE,
Primary Dermal Irritation Study in Rabbits | (55
3
(OECD Guidelines)
<P Ines
Study No. 50202473
ea
/
for M St. Paul, Minnesota
by HazletoLnifLeabSocriaetnocreisesDiAvmiesriiocna, Inc.
Ma3d3i0s1onK,inWsimsacnonBsoiunlev5a3r7d04
February 25, 1985 1985, Hazleton Laboratories America, Inc.
Chemical & BioMedical Sciences Division
01475
Study Yo. Study Location
Test Material
PROTOCOL T2071 Peinary Derma(lOEICrDriGtuaitdieolninSetsu)dy in Ravbits
50202673 HLiafzeleStcoinenLcaebsoraDtiovirsiieosnAmerica, Ipc. 3301 Kingman Boulevard Madison, Wisconsin 33706
3127
Sponsor's Representative Study Director
Dallas D. Zimmerman, PhD Steven X. Glaza
PropSotsaerdtiTnigmetDaatbele CFoimnpalletRieopnorDtatDeate
WWeeeek ooff FFeebbrruuaarryy 2255,, 11998855 Week of April 1, 1985
C01176
onecrive
The objective of this study is to determine the relative Level of primary skin irritation of a test material on rabbits under semioccluded conditions. ALL aspects of this study will confors to the Organisation for Economic Cooperation and Development's Guidelines for Testing Chemicals, Section 404, Acute Dermal Trritation/Corrasion, Adopted May, 12, 1981" and the U.S. Food and Drug Administration's Good Laboratory Practice Regulations for Nonclinical Laboratory Studies? ALL procedures will be done according co Hazleton Laboratories America, Inc. (HLA) Standard Operating Procedures (SOPs)
referenced in this protocol.
Test Materials Physical Description: Purity and Stabiliey:
TEST MATERIAL
T3727. Off-vhite solid. Sponsor has puricy and scabilicy decersinations
Storage Conditions: Test Material Retention:
Safety Precautions:
Store at room teaperacure A30nydauynsusaefdtetresitssmuastnecreiaolfvithlel fbienadlisrceaprodretd. nLeacbeosrsaatroyryprpeecrasuotninoenlswiinllhatnadkleintgheansourbasstlance of gulnokvneosw,n staofxeitcyityg.lassLeasb,oraantdoray cpalrottihcilneg,malsaktex approved for toxic dusts must be worn.
TEST SYSTEM
Bi
Test Animal
Young adult albino rabbits of either sex of the New Zealand White serain,
approxizately 16 weeks of age, will be obtained fron Hazleton Research
COL1L77
2
Products Inc., Denver, Pennsylvania. An adequate number of extra animals will be purchased so that no animal in obviously poor health is placed on test. Historically, the New Zealand White albino rabbit has been the animal of choice for evaluating the effect of chemicals on the skin.
acclimation "Upon receipt, the animale will be taken to a designated animal room where they will be acclimated for at least 1 week before being placed on test (OP-GENB 36). During acclimation, the animals will be examined for clinical abnormalities indicative of health problems (e.g., diarrhea, ectoparasites, cough hair coat, nasal or ocular discharge, evidence of injury, ete.) Any animals regarded as unsuitable for study purposes because of poor physical condition will not be released froa acclimation and the reason(s) will be
documented.
Heati fication Bach animal ia the study will be assigned a permanent identification
umber and will be identified with a metal ear tag (OP-GEND 24). All data collected from an animal will be recorded and filed under its identification nusher.
Housing and Maintenance The following environvental conditions will be maintained in the animal
room used for this study (OP-TARC 230).
o Temperature: 21C 12
o
RAeilratcihvanegeh:umidAittyl:easStO%10+2c0h2anges an hour of Filtered 100% outside air
o Light cycle: 12 hours light/12 hours dark
01i78
3
empecature and humidity will be monitored throughout the study. Variations from prescribed envizonmencal conditions will be documented.
fates husbandey and housing at HLA cosply vith standards outlined in the
"Guide for the Care and Use of Laboratory Animals." Care will be taken to
ensure thet the animals are not disturbed for reasons other chan data collection and routine maintenance. The animals will be housed individually in screenbotton stainless steel cages (heavy gauge) held on racks, with absorbent pan Liners in the urine- snd feces=collecting pans. Pan liners will be changed at Least chee tises cach week.
Feed and vacer will be provided sd libitum. The diet vill be Teklad Laboratory Rabbi Diet. lo contaminants are expected co be preseat in the feed or vater which vould interfere and affect the results of the study.
-
Study Design
:
Tree cabbics will be selected at random based upon health and a body
weight of 2.0-3.5 kg. Each animal will serve as its own control.
erocepuRss Preparation snd Adsiniseration of Test Material
Iventy-fous hours prior co test material adainiscration, the hair will be Clipped From che back and flanks of each animal. The crescent sices will be
the use of any of the aniaals. inspected for interfering lesions, irritation, or defects that would preclude
The test material will be applied to the test area (approximately 6 ca?)
on cach cabbie, in the amount of 0.5 and will be moistened vith deionized "ater. The created ares will be covered with a 2.5-<a x 2.5-ca gavse pacch
01179
.
secured with paper tape and loosely avervrapped with Saran Heap and Elastoplast tape to provide a semiocelusive dressing. Collars will be used co cestrain the aninals during the d-hour exposure period.
Reason for Route of Mainistration Historically, the route of choice based on the method of Draize.
Observations After the 4 hours of exposuce the patches and che test material will be
ceaoved as thoroughly as possible using vater or an appropriate solvent
without irritating the skin. Thirty minutes after removing the patches, the
degree of erythema and edema will be recorded according to the Deaize Technique (Accachaent 1). Subsequent readings vill be taken at 26, 48, and 72 hours after patch removal. Further observations may be recorded, as necessary, to establish reversibility. If irritation is increasing in severity at the 72-hour exsaisation period, observations vill be repeated at 96 hours and at 7 and 14 days, if applicable.
3ody weights vill be taken just prior to test material adainistration and at weekly intervals during che study. Observations sad body weights will be recorded in the study notebook.
Pathology ALL anisals, whether dying on test or sacrificed at study cermination,
will be discarded.
C0150
5
Report Te final report will present a description of the test material, a
description of the test system, dates of study initiation snd termination, a Cabulation of irritation data, and a description of any toxic effects other than dermal irritation.
Maintenance of Rav Dats and Records Original data oc copies thereof will be available at HLA fo facilitate
auditing the study during ite progress and prior to sccepsance of the final report. When the final report is completed, all original paper data, as vell us the final report, will be retained in the axchives of HLA, Madison, Wisconsin (OP-GaN 44).
:
.
Rersmences
1. C"AhceumtiecalDse,rmaSlecItriroint4a0t4i,on/HCaoyrr1o2s,io1n9"8,1.OECD Guidelines for Testing 2 noms
3. DHEW Publications No. (NIH) 78-23 (1978).
4. FDoroadiss,e, DrJu.gaH,., an"DderCmoaslmetTiocxsi,ciAvtsyo,c"tsriAoppnraisoafl oFfootdheandSabfercuyk oOfffCihceisailcsalosf itnhe 8 Tope Kansas, p+ 04-59 (1959).
01181
PROTOCOL APPROVAL
DEST COPY AVAIL ABLE
DaalllaslD.eZid mmermG an, Pu> mn
Sponsor's Repre=sentative
.
SSteuvdeyne DWi.reGce ltaozre We HGarzolueptoLneadLearb,oraAtcourtieesToAxmiecroilcoag,y Inc. i (10698755)
we male = 228-35
01182
?
ATTACRAENT
PRIMARY SKIN IRRITATION SCORING SCALE
1. Erythema and Eschar Formation
No erythema
0
WVeerlyl-sdleifgihntedereyrtyhtehmeama(barely perceptible)
21
MSoedveerraeteertyothseemvaer(ebeeertytrheednmeass) to slight eschar formation
3
Cinjuries in depch)
a
Highest possible erythema score
"
2. Edema Formation
VNoeryedselmiaght edema (ately perceptible)
01
MSoldiegrhatteedeedneama(e(dgreasiseodf aaprperaoxwiemlalt-edleyfi1nemda)by definice raising)
32
Seavreerae oefdeemxapo(sruaries)ed more than 1 mm and extending beyond
&
Highest possible edema score
"
601183
@ S H01A AKZINSLMAEN BTLVDO. N+ LP.sO.oBrOaKT76o45R+EsMAAMDEIRISWCAIOAE 5N3N7,0Ge7ee+(r0e8c)w2r4s1o44s7i1ne+rTcXrm0e3r0s50rWmAiZrArAsLsDmSen0e
Protocol T2069
ATEN
Acute O(ra0lECTDoGxiuciidteyliSnteusd)y in Rats;Femozies 3\
Study No. 50202473
45
cu
f
Nrhe
rd
for St. Paul,EYMinnesota
by HazletoLnifLeabSocriaetnocreisesDiAvmiesriiocna, Inc.
Ma3d3i0s1onK,inWsimsacnonBsoiunlev5a3r7d04
February 25, 1985 + 1985, Hazleton Laboracories America, Inc.
Chemical & BioMedical Sciences Division
01:8
PROTOCOL TP2069 Acute Oral Toxicity Study in Rats
(OECD Guidelines)
Study No.: Study Location:
Test Material: Sponsor's Representative: Study Director: Proposed Timetable
Starting Date: CFoimnpalletRieopnorDtatDea:te:
50202473 Hazleton Laboratories America, Inc. Life Sciences Division 3301 Kinsman Boulevard Madison, Wisconsin 53704 1-3727 Dallas D. Zimmerman, PhD Steven M. Glaza
Week of February 25, 1985 WWeeeekk ooff MAaprrcihl 111,, 11998855
01185
onagcTIVES To determine the acute oral toxicity produced when the test material is administered by the oral route (gavage) to rats. ALL aspects of this study will confor to the Organisation for Economic Cooperation and Developaeat's
Guidelines for Testing of Chemicals, Section 401, adopted May 12, 1981" ane
the U.S. Food and Drug Mministration's Good Laboratory Practice Regulations
for Nonclinical Laboratory Studies.? ALL procedures will be done according
to Hazleton Laboratories America, Inc. (HLA) Standard Operating Procedures
(SOPs) referenced in this protocol.
TEST MATERIAL
Test Material:
3727.
Physical Description:
oft-vhite solid.
.
Purity and Stability:
dSpeotnesromrinhaatsionpsuriotny fainlde.stability
Storage Conditions:
Store at coon teaperature.
Test Material Retention:
dAinsycaurnduesded30tedsatysmaotferiiaslsuavniclel obfe the
final report.
Safety Precautions:
nLoarbaoaraltonreycepsesrasroynnperlecwaiultliontsakeinthe htaonxdilciitnyg. a sLuabbsotraantcoeryofcloutnhkinnogw,n latex SBalsokvesa,pprsoavfeedtyfogrlastsoexsi,c daunsdtsa mpuascttibcele worn.
Disposal ALL waste feed, aninal vastes, pan Liners, and carcasses resulting fron
this study will be disposed of in a high-teaperature incinerator (U.S. Smelting Furnace Company, Belleville, Illinois).
01186
2
TEST SYSTEM nina] Model
Young adule male and female albino rats (approximately 7 weeks of age) of the Sprague-Dawley strain will be obtained fron Harlan Sprague-Dawley, Madison, Wisconsin. Rats will be selected at random from healthy animals that had been acclimated at HLA for at least 1 week. An adequate number of extras will be purchased in order that no animal in obviously poor health is placed on test. The weight variation in aninals used on test will not exceed +20% of the mean weight (i.e., mean = 250 g, range = 200 to 300 ).
Reason for Species Selection The rac is che dnisal classically used due to its small size, ready
availability, and large amount of background data.
Identification Each animal will be assigned an individual aninel nusber and ear tag which
will accompany data collected from that animal throughout the study (op-GeNB 24).
Housing and Maintenance The following eavirounental conditions will be maintained in the animal
oom used for this study (OP-TARC 230). o RTeelmapteirvaetuhreu:midi2t2y:C 4250% 320% Air change: At least 10 changes an hour of filtered 100% outsice air o Light cycle: 12 hours light/12 hours dark
Temperature and humidity will be monitored throughout the study. Variations from prescribed environmental conditions will be documented
01187
3
Animal husbandry and housing at HLA comply wich scandards outlined in the "Guide for the Care and Use of Laboratory Animals."> Care will be taken to ensure that the anials are not disturbed for reasons other than data collection and routine maintenance. The animals will be individually housed in screex-botton stainless steel cages held on racks, with absorbent pan Liners in the urine- and feces-collecting pans. Pan liners will be changed at Least three times each week.
Feed and water will beprovidedad libitun. The diet will be Purina Rat Chow. Mo contaminants are expected to be present in the feed or water which would interfere and affect the results of the study.
PROCEDURES
. Experimental Design
'
Initially, a single dose of 5.0 g/kg will be administered to 10 animals
(five males and five females). If no test material-related mortality is .
produced at this level, no further testing is required. If any mortality
occurs at the 5.0-g/kg dose level, at the Sponsor's request, three or four
geometrically spaced dose levels may be added. Each dose level will consist
Of 10 animals (five males and five females). Animals will be assigned to
groups according to HLA Standard Operating Procedure OP-TOX 42.
Test Material Preparation and Administration The test material will be suspended in an appropriate vehicle. Individual
dosages will be calculated based upon the animal's body weight taken just before administration of the test material and administered by gavage.
01188
"
Justification of Route of Administration
This is the method for aduinistering & known quantity of test substance and has been the route of choice historically.
servations
The animals will be observed individuslly for clinical signs and morcality at 1.0, 2.5, and 4 hours after test material adainisteation. The animals will be observed daily thereafter for at least 14 days for clinical signs and twice
daily (morning and afternoon) for mortality. The duration of observations may
be extended when considered necessary. The time of death will be recorded as
precisely as possible.
Individual body weights vill be recorded just prior to study initiation
and at 7 and 16 days following teat material administration and at death. "Changes in body weight will be calculated and recorded vhen survival exceeds
1 day.
.
Pathology ALL test anisals, whether dying during the study or sacrificed at
termination, will be subjected to a gross necropsy examination and abnormalities recorded.
Report
The final reporc will contain a description of the test material, a description of how the study vas conducted, response data for clinical signs,
mortality and body weights by sex, a discussion of the data, and gross
pathology findings.
'
01189
5
Maintenance of Rau Data and Records
Original data or copies thereof will be available at HLA to facilitate
auditing the study during its progress and prior to acceptance of the final
report. When the final report is completed, all original paper data, as well
as the final report, will be retained in the archives of HLA, Madison, Wisconsin (0P-GEN 44).
REFERENCES
1. OTregsatniinsgatoifonChefnoricEaclosn,omSiecctCiooonpe4r0a1t,ioAncuatnedODreavlelToopxmiecnitt'ys, aGudiodpetleidneMsayfo2r1, 1581.
2. 21 cre 58.
3. DHEW Publications No. (NIN) 78-23 (1978).
:
01190
s BESUCOPY Aagyp
PROTOCOL APPROVAL
Dd
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(10645/38)
mwoio- sd
oe 2258S
)
01191
@Hv HA1AZKZIeLNGLMEAENoTBTLYODO.nNN+ 7w.r 0i.s5o0rKs5or6oni+ensMADIeSerONi,cWas .15n0em+ eern+ eTX oaR Fneeo00
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|
Peinacy yeCLoercditatioenrSttoeued)y in tabbics
study to. 30202473
or se. 2a,wMinmesota
:
AasletoTn itLoibsoeriaacbnocyreisesDiAvmiesriiocna, Tc.
va$d3i0v1onK,inWsimsacnonBsoivnier33a7r04
Tebeuany 13, 1985 1985, tasteton aboraories America, Tac.
Chemical & BioMedical Sciences Divison
601192
PROTOCOL TP2072 Primary Eye Irritation Study in Rabbits
(OECD Guidelines)
Study No. Study Location
Test Material
50202473
HLaifzeletSocinenLcaebsoraDtiovirsiieosnAmerica, Inc.
3M3a0d1isoKni,ngmWainscoBnosuilnevar5d3704
.
13727
Sponsor's Representative Study Director
Dallas D. Zimmerman, PhD Steven M. Glaza
Proposed Timetable Starting Date FCoimnpalletRieopnorDtatDeate
Week of February 25, 1985 WWeeeekk ooff MAaprrcihl 11,, 11998855
01393
OBJECTIVE
The objective of this study is to determine the level of irritation produced following a single exposure of a test material to one eye of albino rabbits. ALL aspects of this study will conform to the Organisation for Economic Cooperation and Developaent's Guidelines for Testing Chemicals, Section 405, Acute Eye Irritation/Corrosion, Adopted May 12, 1981" and the U.S. Food and Drug Administration's Good Laboratory Practice Regulations for Nonclinical Laboratory Studies.' ALL procedures will be done according to Hazleton Laboratories America, Inc. (HLA) Standard Operating Procedures (SOPs)
referenced in this protocol.
TEST MATERIAL
.
Identification
Test Material:
1-3721,
Physical Description: Purity and Stability:
Ofg-vhite solid. Sponsor has purity and stability . determinations on file.
Storage Conditions:
Store at room temperature.
Test Material Retention:
dAinsycaurnduesded30tedsatysmaatfetreiraliwsislulsacbee of final report.
Safety Precautions:
nLoarbmoaraltonreycepsesrasroynnperlecwaiultliontsakeinthe handling a substance of uaknown gtlooxviecsi,ty.safeLcayborgaltasosreys,claonthdinag,parltaitcelxe wmoarsnk.approved for toxic dusts must be
01194
2
TEST SYSTEM Test fnimal
Young adult albino rabbits of either sex of the New Zealand White strain, approximately 14 weeks of age, will be obtained from Hazleton Research Products, Inc., Denver, Pennsylvania. An adequate number of extra animals will be purchased so that no animal in obviously poor health is placed on tesc. The New Zealand White albino rabbit is the animal of choice based upon ite large orbit and nonpigaented iris.
Acclimation Upon receipe, the animals will be taken to a designaced animal room where
they will be acclimated for at least 1 week before being placed on test (OP-GENB 36). During acclimation, the animals will be examined for clinical `abnormalities indicative of health problems (e.g., diarrhea, ectoparasites, rough hair coat, nasal or ocular discharge, evideace of injury, etc.). Any animals regarded as unsuitable for the study purposes because of poor physical condition will not be released from acclimation and the reason(s) will be documented.
Hentification Each animal in the study will be assigned a permanent identification
ouaber and will be identified with a metal ear tag (OP-GENB 24). All data collected from an animal will be recorded and filed under its identification nusber.
01195
3
Housing and Maintenance
The folloving environmental conditions will be maintained in the animal room used for this study (OP-TARC 230).
o RTeelmapteirvateurheu:midi2t1y: 22"50% $202 LMirghtchsanyglee:: Ar12 lheoausrts 10Ligchhta/n1g2eshoaunrshoduarrkof filtered 100% outside air Temperature and husidity vill be monitored throughout the stuay.. Variations
from prescribed environmental conditions will be documented.
Aninal husbandry and housing at HLA comply vith standards outlined in the
"Guide for the Care and Use of Laboratory tnimals."? Care will be taken to
ensure that the anisals are not disturbed for reasons other than data collection and routine maintenance. The snisals will be housed individuslly
in screembottom stainless steel cages (heavy gauge) held on racks, with
. sheorbent pan Liners in the urine- and feces-collecting pans. Pan Liners will be changid at least chree times each week.
Fond usd vanes vi be provided go LBEE. The die vill be Texlasd
Laboratory Rabbi Diet. No contaminants are expected to be present in the feed or water which vould interfere and affect the results of the study.
Study Design Three rabbits will be selected at random based upon healtn and a body
weight of 2.0 to 3.5 ke.
Procebumss Preparation and Adninistration of Test Material
The rabbits" eyes will be examined using Fluorescein dye procedures within 2 hours prior to test aaterial aduinistration. Only anisals vith no sign of
01196
"
corneal injury or eye abnormalities will be utilized. One eye of each animal will be treated with the test material and the other eye vill serve as the untreated control.
Each rabbit will receive 0.1 g (or the weight equivalent of 0.1 al) of solid test material. If necessary, the solid test materials will be finely ground into a dust or powder. The test material will be placed into the everted lover lid of the rabbit's eye. The upper and lover lids are then to be gently held together for 1 second before releasing to prevent loss of material. The eyes of the rabbits will remain unflushed for 24 hours following instillation of the test material. After 24 hours, a vashout may be used if considered appropriate.
Reason for Route of Mministration Historically, the route of choice based on the method of Draize.*
Observations The treated eyes of all animals will be examined for ocular irritation at
1, 24, 48, and 72 hours after treatment. If no irritation or injury is present at 72 hours, the study will be terminated. If irritation is present at 72 hours, additional observations will be made at 96 hours and at 7, 14, and 21 days. If at any of these time points there is no irritation, the study will be terminated. If injury is still presen at 21 days, the Sponsor will be contacted to determine whether the study should continue or be terminated. After recording the 24-hour cbservations, sodium Fluorescein my be used to aid in revealing possible corneal injury. Irritation will be graded and scored using the Draize technique (Attachment 1).% All eye abnormalities will be recorded.
01197
5
ALL snisels that have a damaged eye producing undue stsess or discontors With be saseiticnt for Tumene Tessore 482s sosmsieing with the Sponnse. ] Sod watshis wiTE be senesisd gots 5 tase spnerial atetnlstraion, and at. Weekly intervals throughout the study. Ghservacions and body weights will be recorded in the study notebock. Pathology
AL antaain, Winther dyes oF sarmtiient at Atoty eesminutiony wilh be ttocertet.
Report
)
The inal segore will present. desveiptige af she vast natectal, 8
description of the teat system, dates of study inisiation and serwination, &
smmary table shoving the irritation dats ak each chasrvation period, end snp
sgental, shosevations thas were sevseieds
Seiten stn Jus ad Bunt
}
Original data or copies thereof will be available at HLA to. facilitate
auditing the study during its progress and prior to acceptance of the final
Foport. When the final repost fa completed, 411 selginal pager data, os well as the final report, will be retained in the erchives of iA, Medison,
Wisconsin (OP-GEN 44).
.
01198
6 REFERENCES 1. "Acute Eye Irritation/Corrosion," OECD Guidelines for Testing Chemicals, Section 405 (vay 12, 1981). 2. 21 cer se. 3. DHEW Publications No. (NIE) 78-23 (1978). 4. CDoesaimzeet,icsJ.-H.D,erAmpaplraTiosxailcitoyf, tAhessSoacfieattyioonfoCfheFmoiocdalasndinDrFuogodsO,fficDriuagls,s oafndthe U.5., Topeka, Kansas, pp. 43-51 (1959).
01199
, BEST COPY AVAIl ABLE
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01200
PROTOCOL ~ ATTACINENT 1
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01201