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357
+
Chemica & Bioadiet Sconces
PH6O0 N24E47 + TUX TESS NAZRAL
Division
MDS UD
FINNAALL RERPEOPFORT
PJTAoNNXEIISNCEOOLToGABLYERMSISONENIRNVGICE&SMANUFACTURING COMPANY TERS sion savpLes 1-352 PURCHASE ORDER NUMBER: T357842, REL. 4513
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on PE . ;
Sk
SAMPLE NUMBER: 50503501 SAMPLE ENTERED: 05/15/85 REFORT PRINTED: 06.21/85
ENCLOSED: PSBRaAIiUMADRREaYPtOaRETYAEPPEINRDRIIXTATION - METHOD, SUMMARY
sioveo: SiBEorm e1, eGldaza. Woe
ASCTUhToEv TDIoRxEiCcTOOLROBY
dcatre GRABS
BY AND FOR HAZLETON LABORATORIES AMERICA, INC. BeiseDAnTA FROeR.TTHeISoSTTOUND,Y AWRIESCOKNESPITN.ON FILE AT HAZLETON LABORATORIES
01078
BD HAZLETONoroee mwaseoncWnnReG7 FOCNhEemoicahl& 7loa+ dLiXnT!o0S8caWnAcZesAD5iv0is0ion
ShPLE nurER: 50503501 spies 132
ie 2
GED EYE IRRITATION assgeoaecttriivvgmesreTTeoxopdosdeuetrteeerrommfiinnge t0tehe Iloevel
ofi asslernaCiarvtreiaatararatattlieoinso1nobpaironongdgIurcDrreeaidvbtebailtftoiospolmnle'onwitn'gs
sGueicdoerldiinnegts ofothreTOerngtaendisaDtaimoinoHna?r ES
TesTPrtEyN slHeestlarDieO aztesripTS t3i7o52n2,: 2Sarrrouonugra9nTHula1r0s)oliddna stebitivy determinations
essBvtoatutiaZomaeinntncialamlagsaneldsYYioonniuutenntggt emaspdduulrltettue rrareebbbbitiaets(nP(spPprToxirmstoeenltyraad1i4 luesadIsnnkdudsciwvtoaifitdoeuanragsl,e)sopnordifonvhiestdlchdeerdeens
Cone ee
ret least 7 save.
ITTehnrdeoeinfwaocacrlittmatheedetdeasnatin.nineslTlshse,, ewuesiimgghhiinnegg effrroonme2223e7333
1tF0oia5a0r02e4s,c5e3.,intuhedirynee
2pc4rhoocsheeodnuerrssetsp.rior
LOntoy ethmosreaandimalss awmith ne ig ol o Tereairy aCrinorreistpeokndjionngvasrosr w1eo3e-d:
fosuenenftoorn SpSpeecciieess SSeelleeecttiionos Tehe NewaZoeeleandanUdnitneonailgbniennoterdasbiirtis.is the
besToSpmaeeeriaattesiiooodnnnanaongdfaadAmd0imdniiemnsmitrseattrSiaotneiontooeffTTeestntMatio0i1r0k1i2aeilta:on]0T.hst3eea5c7ds5ssamvpasolrhnemoiuinlunedsdsivntoihdtedousaetwlderiogo5dh2eotdse
IrScqaIouDttenmroeinn8ettdssoln |oEwaSecarhhceehLriardbaTbboibftitornereceecieevyieev,dedSHe0ia0n.i1a3HonlfoifaIStenheartleaesttsermaaoltaerrasivaealesneeprilvyaicnehgdeldo2n0 the
Lreagerrenfeer oame a frEedLntSetsussohF.material ond hen relsased:
C01079
HAZLETON sonorroe smomwoanceom Tm FHChoenmiEc1a&7BlobTaXdiRalSoaaRnces DAiOviSsiDon
-- grees vam seco EVE TRRITATION
pce continue
StEthe Zatourvomrtesitnign,g,ssooddiiuumn [luLoerasOcEeRinSiunsseusiende Stoeorseidd sinneerreavienagling
reeratrean, ou stuty termination sl) aninals ware suthanatized and robmrhraaiBtuazet,,r3eSkuite,,de""eAggmporeriasieslaloaff thhee SeSfaStayeofosffoECtshheeymniecRals18in FRooEdsSDruBgPRs,eine
01080
HAE ZLEe TON rowrosmSenoovncwnees 7 HhOamboiNs4h ES1uedXeTSeRiiAes oWErRion
chrpLE nureER: 50503501 sme: Tam
we 4
OECD EYE IRRITATION
conTIuED> sonny
ETfesteAmniAinmalHCAlbina o rabba itsam- eNetu:Zearleanrd UDnaimtoen PR
Tommarature and Humidity of Animal Rooms 2211t0o T23 ODegrReesSC.ifumiaiey
Test Hotarials T3752 Dote Test Started 15/29/85
dete Test Complated: 06/01/85
PRIARY EVE IRRITATION SCORES
OBSERUATION PERIOD
wntAaEin--i
i 281 etouersr 4 tour:
10b5.t77 2
+ fTThheeleprmaiesrneyr eEEyeeiL Itrrite etion Sceareiismtahae rtotoaFlaneyiemalierri(t3)atia4onmescchore
EE te nate No corneal irritation was observed during the study.
01081
I HAZLETON vemrmmwomenee Chamica BoMedical Siances Ohision "
3901 KINSMAN BLVD. + P.0. BOX 7545 + MADISON, "WISCONSIN 53707 + PHONE(608) 241-4471 + TLX703956 HAZRAL MDS UD.
PAGE
soni: T3752 SAMPLE NUMBER: 50503501
asco eve IRRITATION
continue) Indiviual EvTnaivrivsit1ation Scores
fvmeissetl ObeGseerrnutisotnion mime
GCoommmeazs FSeagrs IIrEis SFeRorEs ACoVnjEumsNtiEves wSceereen 0 bn051 5z0oazooaopn ls8
eS gedrusef 0 3083B0058 000o8oo0
ors gaveeeerR Guus
1p 0 81J 80DS2 R F0SUE5s S5E o0S8E a 6nSO 0opnsooS-
cot dggidruueesse 0p 0 30 80 o80 nd 0a05z0% o10aoh opo6zooponn zm000
codiun FluorTsoebsiien2Examination
FfFneoaiiurarlls
ndieEse eruation Ne
PearifNoeedeur
He
hed
"Es
HAEESS == NNooestteaiinn rTeoteTntitonion (area of cornes involved):
RetHoranoOcregsatntiasasttiioenn. Ffoorr EEoenaneic Cosperationitaned EDveevslIrorginteanttisonGCuoirdreolsiinoens,
2.
foroiostied is rorarezdetBS eenmoecrHitd,e aepprDaeeirsmea]l
oTfOTthAeL SaFfoRpeaattiyoam,oifaKtCarnjeoemnsi,coaflpspF.ooidn$7eF0no3dssD(,i1v9aD5r9)u.gs,
601082
PAGE 6
QUALITY ASSURANCE STATEMENT Primary Eye Irritation Study io Rabbits
Study Fo. 50503501
Tb1h0yeathcrecepoaorsrdstaingacnseevdhieQtruehailntihatetytGAaoscohsdeudrLsanbfcooerraUttnohiertyaboPforvaHeca-tcmielcneettioRonengeLudalbasottriuaodtnoysrihaesasssAbemeteernfiocrraet,vhieIinwnce.d dt2e1hescCcrFoRinbd5eu6c.tt3h5eof(abu)tthheo(6r)iszte(u7dd)y.meantdhItodthshaastanbdteheesntraenfdpoauornrddtedotopdeaarctacatuiarncagtceuplrryaotcieedldeyuartreiesffylfeocaltnldov/teohdre irnaw dcCoaontndaduuccottfedtofhtehtelhaifbsoolrslatotuwodiryynsgosdtiundshypa.esctsiuFobunrmstihtoetfremdotrhweert,ietstcehtneinQrgue.apfloaircttiyslioAtfsiseussraaiudntcieiloiUsznpeiedtctihiooasntsheto the study director and/or msnagemeot.
C bate of Tspection Type of Inpection
5/21-23/85
Process Audit
6/10/85
: Report Review
Date Tnsued to Hanageneat
5/23/85
6/10/85
.
LDeiansa iE. aSkal.iteHkyalil 2 Inspector, Quality Assurance Unit
Date S257
01083
9]
Oo
"PROTOCOL = ATTACHMENT 1
sama 01 GSaamnois
dseegrueenooffsnnsnryeCCartomefssmmeasnsddaeerneny khe2nsBforEFDstS) 1
. :
a pe a iovhat iteeofsarrsitr ,r vviifosntaknilise,toso fiareiof 7su s
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o
ass
total gion + 10
|
mama
TST 1oAr)lpeZdisoee tmamzsae(nf( lvosrir eesetrIvef eappaelle, peer nb,ers satlfssiitemarejemmeettsiirnvTaeeeeeaellyn)a ) :
SiSmr0rt)uoieiDelmama ebaisasTyaa mseermwesC-am2)eSiweemen nCgb oionsss wte ----} -------- :|
T Tuipmenmmmtn nTr osfethle e TlaCoeeaessasetdrotiriie rressSeJutsaienme mets ,1
Tonics vi emeesoothalnaswwdt biir foodd setneiele
T oe ote [ mI o fr.tL h a7 2 a0A mm ofa3sar abatan fo She
01084
'0
PrEi ye Im rritaatir onTy est
Inseial Sodium Pluoresceta Bam aod Antnal Body Weights
Test Compound _3 T=252
PH Result
nA
Dose of lg ue
BT No.
weave.
Seso3Se)
_[6l3
Dose (al)
WA
Dosed By __dK Date 5725/6
Date Animals Received _5-2/- 85
Source: Hazleton Rescaven Products
Reviewed By Fr Date Shes
Esod7 RvetgE uee
Ra
oping] T NWTm [RRTE|
ost owe [a [233s [N\ | [|
sios|or| we[A aaa | \ | [7]
.
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0
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~~
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NTT INT]
PINTTNT
FT NT
NT]
T_T NO]
TT I~ 1 1
|
F NT F IN
omclox [smn[ek | ce | |[N_|
owner [one|e | ae |[TN
lussg9sfn[520[saa sas [| TN
lscusomr -- gpen liseg|[|
#
10
=
NSeogdaicuimveFluorescein
Examination
TimeTiomfe feosftDoOvbinsgtr: v10a:b4i5o:0inmuscakm&-c2e.7-95
Oo
= tot Aoplscable
Sa095
HE
:
601085
Prisary Eye Irritation Test Observations
Ortecst CompR ound 1 ig325 cnr S 2 wmwh.3250350)
A /A' BE OTR ee WE tenn Washed AL A Seats terleviny instillation of test
LL Unvashed
OBSERVATION PERIOD:
/_hour
=r JOIOIOINIOIO PI
meee [ole olNL [0lo |o IN 1 |
mi[l y=] [o IN [|
of LL TN oO
padsene
{
wen 1a[+ 12 |[XN|
ome 1010 137| | IN__]
Co pmerestozenlA/F(v8 vm | | [N\_|
Poise Lox TexLee 1 1 N1
een LxleeTeo I 1 1 NI
ne A = Purulent Discharge
.
B = Clear Discharge
C = Petite Hemorrhage
D = Blanching
IRJ = Injected
NEG = Negative
o Reviewed By:
SO
= =
G= B'= 1= NA =
Corneal Epithelial Damage, Corneal Epithelial Damage, Corneal Epithelial Damage, Pannus Corneal Neovascularization Not Applicable
Peeling Piling pitting
ues DTD toe evirton sesees [Oith
-
601086
Primary Eye Irritation Test Observations
ALR vant LBsez lz Si teaeit Test Coapound |= 3FSR
O rearBight
2 No. SO50350)
Geoup ALA.
-
MA woof AJB tor AA seconds
OBSERVATION PERIOD:
24_houy.
= 00000 bait coo Head
Se La oraes = gpacie
be
O D2
Q
lo To lolNT |
To lolIo NTl|
Nn APR A OC
Redoess.
Q
0
Q
gmc 10lolo|
1
NX |
ese |010lo [1 IN|
bowie beware
{op 1po[po|[TN] |ol pl2 | 1 NJ
A = Purulent Discharge
"
B = Clear Discharge
C = Petite Hemorrbage
D = Blanching
NIENG == NIengjaetcitveed
POS = Positive
=
7= G=
B=
HA1 ==
Corneal Epithelial Damage,
Corneal Epithelial Damage, Corneal Epithelial Damage, Pannus
HCoortneAaplplHiecoavbalsecularization .
Peeling
Piling Pitting
0 Revieved By:
lSathtedater L395 eye trrication scoreD: OsTIA
-
01087
Primary Eye Irritation Test Observations
O nTeset CeopouRndig| i= 3 FS
cr all 81 No. SO50350)
LB vr LB ts elie taro of ty eted
MA = on TA er AUB seconds
OBSERVATION PERIOD:
H hours
= RS)JOOONIOI0)\ ]
ee LTT ke oF Lela TIN] oO
loTo To[NT| 1 po loloI [TN [ |
--
00
gm Jolo[oo |TN1
eae |0 10[0|[IN|
bowietee {ck Toe[ce|[1N| lecwrsrr Loxlox TaeI[TN] hue Jas loals |s|le 1z N
A = Purulent Discharge
.
B = Clear Discharge
C = Petite Hemorrhage
D = Blanching
IN = Injected
NEG = Hegative
POS = Positive
E = Corneal Epithelial Damage, Peeling
7 = Corneal Epithelial Damage, Piling
G = Corneal Epithelial Damage, Pitting
B'= 1=
Panmus Corneal
Heovascularization
NA = Not Applicable
.
0 Revieved By:
20% pate: PBS eye terication score:00Ta IT
'
1088
Primary Eye Irritation Test Observations
O TreseteCrompoLundi[=g3nFtS
AR washed _A/ A
in
wr No. SO50350]
ral
ts ew ad us
ZL Unwashed
= H00R00 frail <eeeeeeeeee> Head
OBSERVATION PERIOD:
73 houv's
loloTo NT1
be
1 ololo I INT |
oO
Redness
Q
0
0
J
gee 10lo[0 [N_1
ase |0 |0[OT IN|
A = Purulent Discharge
N
B = Clear Discharge
C = Petite Hemorrhage
D = Blanching
IMENG == NIengjaetcitveed
POS = Positive
0 Revieved By:
Sh
= Corneal Epithelial Damage, Peeling = Corneal Epithelial Damage, Piling G = Corneal Epithslial Damage, Pitting B'= Panous
NA1 == HCootrneAaplplNiecoavbalsecularization
*
pacer 1038S eye sevication scores Qe) Ti
.
i
601089
@ HAZLETONLABORATORIES AVERICA INC.
"01 KINGMAN BLVD, + P.O. BOX7545 + MADISW1O5N10,7 + 608)2414471 + TLXT0058HATRALMDSUD
PROTOCOL TP2072
primacy Eye Irritation Study in Rabbits
(OECD Guidelines)
TEE
FaSRESELE,N
|
gn
HAY2
810g
1
}
Study No. 50503501
EEE J
SR
for sc. Paul,MMinnesota
by
Hazleton Laboratories America, Inc. Life Sciences Division 3301 Kinsman Boulevard Madison, Wisconsin 53704
Hay 21, 1985
1985, Hazleton Laboratories America, Inc.
Chemical & BioMedical Sciences Division
01090 19
PROTOCOL T22072 Primary Eye (IOrErCiDtaGtuiiodnelSitnuedsy) in Rabbits
Study No. Study Location
Test Material Sponsor's Representative Study Director
50503501
Hazleton Laboratories America, Inc.
Life 3301
KSicnisemnacnesBoDuilveivsairodn
Madison, Wisconsin 53704
1-3752
Janine Gleason Steven M. Claza
Proposed Timetable Starting Date Completion Date Final Report Date
Week of May 27, 1985
Week Week
of of
June June
3, 1985 24, 1985
01091
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 cabbits. ALL aspects of this study will conform to the Organisation for Economic Cooperation and Development's Guidelines for Testing Chemicals,
Section 405, Acute Eye Irritation/Corrosion, Adopted May 12, 1981" and che Principles of Good Laboratory Practice.' ALL procedures will be done
according to Hazleton Laboratories America, Inc. (HLA) Standard Operating
Procedures (SOPs) referenced in this protoco.l
Mentification Test Material: Physical Description: Purity and Stability:
Storage Conditions: Test Material Retention:
Safety Precautions:
TEST MATERIAL
3752. Brown granular solid. dSeptoenrsmoirnahtaisonpsurointyfialned. stability Store at room temperature. rAentyurunneudsedto ttehset mSpaotnesroiral30wildalysbeafter issuance of final report. nLoarbmoarlatnoreycepsesrasroynnperlecwaiultliontsakeinthe htaonxidcliitnyg. a Lsuabbsotraantcoeryofcloutnhkinnogw,n latex msalsovkesa,pprsoavfeedtyfgorlastsoexsi,c daunsdtsa mpuascttibcele
01092
2
TEST SYSTEM Test minal
Young adult albino rabbits of either sex of che New Zealand White strain, approximately 14 weeks of age, will be obtained fron 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 test. The New Zealand White albino rabbit is the animal of choice based upon its large orbit and nonpigmented iris.
Acclimation Upon receipt, the animals will be taken to a designated animal room where
they will be acclimated for at least 1 week before being placed on test (0P-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, evidence of injury, etc.). My animals regarded as unsuitable for the study purposes because of poor physical condition will not be relessed from acclimation and the reason(s) will be documented.
Identification Each animal in the study will be assigned a permanent identification
nusber 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.
01093
3
Housing and Maintenance
The following environmental conditions will be maintained in the animal
zoom used for this study (OP-TARC 230).
o
RTeelmapteirvaetuhruem:idi2t1y:C #250% 320%
.
o LAiigrhtchacnycglee:: At12 lheoausrts 10ligchhta/n1g2eshoaunrshoudrarkof filtered 100% outside air
Temperature and humidity will be monitored throughout the study. Variations
from prescribed environmental conditions will be documented.
Animal husbandry and housing at HLA comply with standards outlined in the
"Guide for the Care and Use of Laboratory Animals." Care will be taken to
ensure that the animals are not disturbed for reasons other than data
collection and routine maintenance. The animals will be housed individually
in screen-botton stainless steel cages (heavy gauge) 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 be providedad libitum. The diet will be Purina High
Fiber Rabbit Chow. No contaminants are expected to be present in the feed or
water which would interfere and affect the results of the study.
.
Study Design Three rabbits will be selected at random based upon health and a body
weight of 2.0 to 3.5 kg.
PROCEDURES Preparation and Administration of Test Material
The rabbits' eyes will be examined using fluorescein dye procedures within 24 hours prior to test material aduinistration. Only animals with no sign of
01094
4
corneal injury or eye abnormalities will be utilized. One eye of each animal Will be treated with the test material and the other eye will serve as the untreated control.
Each rabbit will receive 0.1 g (or the weight equivalent of 0.1 ul) of s0lid 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 1id of the rabbit's eye. The upper and lower 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 washout may be used if considered appropriate.
Reason for Route of Muministration 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 vill 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 present at 21 days, the Sponsor will be contacted to determine whether the study should continue or be terminated. After recording the 24-hour observations, sodium fluorescein may 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.
01095
.
5
ALL aninals that have a damaged eye producing undue stress or discomfort will be sacrificed for humane reasons after consulting with the Sponsor.
Body weights will be recorded prior to test material administration and ac weekly intervals throughout the study. Observations and body weights will be
recorded in the study notebook.
Pathology ALL animals, uhether dying or sacrificed at study termination, will be
discarded.
Report
The final report will present a description of the test material, a description of the test system, dates of study initiation and termination, a summary table showing the irritation data at each observation period, and any special observations that were recorded.
Maintenance of Rav 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 (OP-GEN 44).
01096
6 REFERENCES 1. "Acute Eye Irritation/Corrosion," OECD Guidelines for Testing Chemicals, Section 405 (tay 12, 1981). 2. LOarbgoarnaitsoartyioPnrafcotricEec,onAommiecxC2o,ope19r8a1t.ion and Development's Principles of Good 3. DHEW Publications Mo. (NIH) 78-23 (1978). 4. CDroasimzeet,icsJ. -H.D,erAmpaplraTiosxailcitoyf, thAessSoacfieattyioonfoCfheFmoiocdalasndinDrFuogodOsf,fiDcriuaglss, oafndthe T.S., Topeka, Kansas, pp. 49-51 (1959).
01097
7 PROTOCOL APPROVAL
Taing Cleasnone Gla
S3pMonsdr's Representative
Steven M. Glaza . GSrtouudpy DLeiardeecrt,orAcute Toxicology Hazleton Laboratories America, Inc. | (1209/25)
mee 5[a4[85
Bate sas
01098
is
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e T Tpetas tiE tiyo d ieI n oir vp SoRA e TeTT
E fSIaaiStESFm aR N PES s ReTa e e E me mm } } e
ares
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.
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des Se ee
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a Te
ts
axs
Total Mazimm 10
3
iES SSoR)RfeSuSemRAee m ias elpeuse tem m nomnpTaeele slem SSrHEvAn e eETys ) J
mE (8)anhmeE lsmisr eRetEi : I r er T a
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tET SE ek oe ELLL fo rn eA Ee
01099