Document 3Qa9Lqpd111EmL0mJvG7ELZnJ
wWlIS gC eoOnNsShIN y
FFIINNAALL RREEPPOORRTT
RWRooggeerr
G.
G.
Perkins,
Perkins,
PhO
PhD
TT83Mouox1xi1iccdooilnloogggyy22SS0e-er2rvv6iic0ce2ess
SBtu.ildPianugl, 2W2N0-2E$5-01244-1000
St. Paul, MN 55144-1000
HHAWII NNuummbbeerr:: 0011110044119388 SSaammpplele:: TT--55229988
Study Title:
Study Title:
PPrriim Smtaaurrdyyy EEoyyfee 1II-rr5rr2iti9at8taitoiinno/nRC/aCobobrrrirotosssiioonn Study(OoEfCDT-G5u2i9d8eliinneRs)abbits
(OECD Guidelines)
SSiiggnneedd::
Nore S WN SStteevveenn MM. . GGllaazzaa
Study Director Study Director Acute Toxicology Acute Toxicology
Ne. Ae
0
ASA Daattee
Phone
608-241-4471
22778877..00000011
Fax
608-Z4 ~-7227
I
EEx2;;h7i8i81b7~iitt
) W_UNO1241251 3M MN01241251
WWIIS SC COONNSSIIN N + ESE
HHWW]I NNuummbebre:r" 0011110044119988 SSaammppllee:- TT1--55229088
Acute Tosicoloay
Acute Toxicoloqy
Steven 1. Glaza
Steven M. Glaza
SSStetuucddtyyionDDiirSreeucpctetoorrvrisor
Section Supervisor
SSSttteeuvvdeeynnCo8R.o. rdSSioonrraeetnnossoronn
Study Coordinator
PGParatotruripicciiLaaeadPpeaarddgghhaimm
Group Leader
SRShehaparoreernnt CL1.o. orHHdooivwneearrtyyor
Report Coordinator
RS
PPaaggee 22
Ke peRsoEL KEY PERSONNEL sborstory Animal Veterinarian Laboratory Animal Veterinarian Cindy 3, Cary, ow Cindy J. Cary, DVM
DDiipplloommaattee,, AACCLLAAMM
contents
CONTENTS
key personnel 2 Key Personnel Bettie g Objective Sa aterian 3 Test Material Toit Site 3 Test System Peaesiees : Procedures Summary of Results : Summary of Results BiEeersion S Discussion Soterences 5 References Raw Data Appendix IH Raw Data Appendix
PPaagqee
2 3 3 3 4 6 9 9 10
22778877..00000022
Uniled Kingdom
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3M MN01241252
WISSoNS IN
Wl Nanbers 01108158
HWI Number: 01104198
SSaammpplele:' TT--55229988
Page 3
onsecrive OBJECTIVE Tne objective of this study as to assess the relative level of rritation/ The objective of this study was to assess the relative level of irritation/ Coreen arsctloriToeutdna single exposure of a test material Fa ne ere corrosion produced following a single exposure of a test material to one eye Tone ee of albino rabbits,z
TEST TERIAL TEST MATERIAL sent fication Identification The test satel vas fdentified as T6258 wd described 35 an office The test material was identified as T-5298 and described as an off-white Tots liquid.
bursty and stp iny Purity and Stability Sponsor assures responsibility for purity and stability determinations Sponsor assumes responsibility for purity and stability determinations reins wnaar' Seat condi rons) (including under test conditions).
Storage ang setention Storaqe and Retention Tne test materia) was stored st roon temperaturs, Any unused material will be The test material was stored at room temperature. Any unused material will be
ddiissccaarrddeedd aaccccoorrddiinngg ttoo HHaazzlleettoonn W Wiissccoonnssiinn ((HHWWII)) SSttaannddaarrdd OOppeerraattiinngg PPrroocceedduurree ((SsoOpP))..
Safety pescautions Safety Precautions Norsal handling procedures were used according to WHI SOP. Normal handling procedures were used according to HWI SOP.
Tact mim Test Animal
Test swsren
TEgT SYSTEM
AAdduulltt aallbbiinnoo rraabbbbiittss,, HHrraa::((NNZIWW))SSPPFF,, wweerree pprrooccuurreedd,, m maaiinnttaaiinneedd iinnddiivviidduuaallllyy iinn
Sireun botsin Saobs In' sessersture' ans humiaiey Control 6d. quireers, provided screen-bottom cages in temperature- and humidity-controlled quarters, provided $5653 So water 29 113itom and 5 Seasored mous) of Nigh Fiber Rabbit Chie access to water ad libitum and a measured amount of High Fiber Rabbit Cho~#~ TSSEE, Porina mills, Toco and Revd: for anace ination period of St Teast #5326, Purina Mills, Inc., and held for an acclimation period of at least Tay An huSbanary' and hosing at MHL Comply with standards outiinec in 7 days. Animal husbandry and housing at HWI comply with standards outlined in
tthhee ""GGuuiiddee ffoorr tthhee CCaarree aanndd UUssee ooff LLaabboorraattoorryy AAnniimmaallss"".~. IIff vvaarriiaattiioonnss ffrroomm
he prescribes environmental cond] ions xisic, hey vere documented and the prescribed environmental conditions existed, they were documented and ConsTiered Uo have no effect on the study outcobe. ho contaminants were considered to have no effect on the study outcome. No contaminants were Scpacted 0 have Seen present in the F464 of nacer Which would have Jmeerfered expected to have been present in the feed or water which would have interfered SER Fretted The vERuTTS of ene shia with or affected the results of the study.
22778877..00000033
awmorzatas 3M MN01241253
2 WisEeONSILN
HNI NNuummbbeerr:: 0011110044113988 SSa~mmpplele:: 1T--5522988
PPaaggee 4
wTTewwrooemmacalhleeoseaannndd atoonneeranffedemommaalleeandaaccmccalliiimmnaattateeiddnedaanndiimmuaralilsns,g, wwteheieigghhsitinnuggdyffrrioonmmt2h2e,,5500s22anettooma22n,,5n59e94r4 gga,s, wFtfooeersrret tthhmceeehtoesaareccinccallliiammt aaatdrtaiimonoidnnnoimsppteerrarianiootdddi.o.mnaiTTunhshteaeiningaaenndisim moaddaliulsusr'ni'ngeefyyleeuthssoerwewseserctrueeedinyeexxaadinymmeiinntheepeddrocooseannmduetthrheeemsa.ddnaanyyeOrnbbleaeyfsfoorree wtttheehorossesteemiaadanentiniemmtraiaialflssil edwwaidittbm hhy innnaooinsitmssraaiiglgtninonnuoofmfbueoosrcicnuuglalaanrdsrocdiinoinurjjmuruerrysyflpuoooonrrrdeiiisnrrrgcrieitatienaattrioidoytnneagwwpereorreeceduususeerded.s. . AAOnniinmmlyaallss
were identified by animal number and corresponding ear tag.
Justiiffiiccaattiioonn
for
for
SSppeecciieess
SSeelleeccttiioonn
HH biaissstetdoorriuiccpaoalnlllyyi,,ts tthhleeargNNeeewworZZbeeiaatllaannaddndWWhnhioitnteepigaarllbebniintnoeod rraaibrbbibsii.tt iiss tthhee aanniimmaall ooff cchhooiiccee
based upon its large orbit and nonpigmented iris.
PPRROOCCEEDDUURREESS
PPrreeppaarra'attiioonn
of
of
TTeesstt
MMaateterriiaall
wTTahhsee
dtteeetssett rmmmiaanteeterdiriaatlol
wbwaeass 6.aa8dd.mmininiisstteerreedd
as
as
rreecceeiivveedd..
was determined to be 6.8.
TThhee ppHH ooff tthhee tteesstt m maateterriiaall
Ireatnent
Treatment
vEEaeaccrhhterrdaabbblbioitwterrreecc1ee1idivveeoddf 00t.h.11e nmrLiLghootff etthyheee, uunwndiditihlluuttteehdde tlteeesfsttt mm eayateetersrieiaarlvl inppgllaaccaeseddthiinenttoounttthhreeeated
cpecorvoneetnvrrtetorenlod.tl. lloowsTTshheeer oufulippdpmpeaetrorefraainnthaddle lloraowinwgdeehrrttl1hi1eeddnysser, wweelwererieeathseggdeteh.nnettllyyTlehehhfteelelddyeeyesttooggosfeeettrhhvteehinrerg rffoaoabrsrbitIIhtessseecurcoeonnnmtddraeianttoetoedd
Unflushed. prevent loss
unflushed.
of material
and
then
released.
The eyes of the rabbits remained
RReeaassoonn ffoorr RRoouuttee ooff AAddmmininisisttrraattiioonn HH Oirsiastitozoreir.ci'caallllyy, tthhee ooccuullaarr rroouuttee iiss tthhee rroouuttee ooff cchhooiiccee bbaasseedd oonn tthhee mmeetthhoodd ooff
Draize,-
OObbsseerrvvaattiioonnss
TT9h5hee hottrurereasa,tteeddandeeyyeeDssayswweer7ree aoondbbssee1r4rvveeaddfteffororr toorcecauutllmaaerrntii.rrrriitatattioionn aatt ]1,, 2244,, 4488,, 7722 aanndd
96 hours, and Days 7 and 14 after treatment.
AAitnt rtthheeevea77l22i--nhhogouurpr,,ossaainndbdleDDaaycy-o-77rneaaannldd --i11n4j4urrrye.eaaddiinnIggrssr,,itasstooiddoiiunumnwafflsluuogorrreaesdscecdeeiinnandwwaassscouursseeeddd ttoo aaiidd
aainccccoroerrdvdieinnagglinttgoo
the Draize technique. possible corneal injury.
the Draize technique.
Irritation was graded and scored
22778877..00000044
I3MM_MMNNO0T1224411225544
: WW isIS c C oO nN sS tIyN
WEAN
HHWHTI NNuummbbeerr:: 0011110044119988 SSaammppllee:- 1T--55229988
+CORNING irSvcsComune
PPaaggee 55
AAinnniitmneaarllvsaslswweerrteehrwwoeeuiigghghoheuedtd jjtuuhssett sbtbueedffyoo.rree tteesstt mmaatteerriiaall aaddmmiinniissttrraattiioonn aanndd aatt wweeeekkllyy
intervals throughout the study.
TTeerrnmiinnaattiioonn AdALitsctteaerrrm dmeiidnn.aattiioonn ooff tthhee eexxppeerriimmeennttaall pphhaassee,, 2a1l1l aanniimmaallss wweerree eeuutthhaannaattiizzeedd aanndd
discarded.
SSttaattiissttiiccaall AAnnaallyysseess NNoo ssttaattiissttiiccaall aannaallyyssiiss wwaass ppeerrffoorrmmeedd..
ocation of Raw Data and Final Report
Location of Raw Data and Final Report
oTTfhhee HHrrIaa.ww ddaattaa aanndd aa ccooppyy ooff tthhee Ffiinnaall rreeppoorrtt wwiillll bbee rreettaaiinneedd iinn tthhee aarrcchhiivveess
of HWI.
22778877..00000055
U nit e d
Kin g d o m
FIX
BOB-2&1-722;
I3MM_MMNNO0T1224411225555
e WB W ISIS R ECOONi NSSIINN
HHWII NNuummbbeerr:: 0011110044119988
Sample: T-5298
Com src rr
PPaaggee
SumARY OF RESULTS TSTeeossuttrceAA:nniimmaaRlla::zleAAtllobnbiinnRooeseRRaaarbbcbbhiittssPro--dHSuHUrcMratMa:sA:,(R(YNNZISWOnF)dPeSsPREFEKSUaLlTaSmazoo Mi BSaotuerceR:ninaHlaszleRtecoanivReeds:earch16P/r0o5d/u9cts, Inc., Kalamazoo
Date Animals Received: 12/05/90
Start ate (In-1ife): 12/27/50
Start Date (In-life): 12/27/90
enc Date (In-Life)s
End Date (In-Life):
01/10/31
01/10/91
AAvveerraaggee PPrriinmaarryy EEyyee IIrrrriittaattiioonn SSccoorreess*t
OObbssSeeerrrvviaaettsiioonn
AAvvseeorrraaegg.ee
2PI1 eroH4iouourhdr
S11c555o..000re
37i4272842 hhoHHHooooauruuurrrrr
805477...713073
[b9D6aa5yr4H?o70ur
a411..s373
Day 14
0.0
+
TGTsThohhcaeesorreaer.aavvvaeefftrrooiaarroggneeaal}lppperrriittimmhnoaaeedrryydannieieeymyeaaellssiirrGdrriiiivvttiiaaddtteiiedoodnn bbyyssccoottrrhheeee
nifssumbttehhere
number
ottfoottaaallnimeeayyeles iirr(3rr)iittaaatttiiooennach
of animals (3) at each
observation period.
Phone 600-241-4471
22778877..00000066
F~x 808-~41-7~27
S_uNor241255
3M MN0124i256
2 MISES LY
= WE SURNAINS
HHWKI NNuummbbeerr:: 0011110044119988
SSaammppllee:" TT--55229988
+ CORNING snSees Samat
PPaaggee 77
amieAuNmnumibmbeaerlr SSeexx
FF3355113366"%
MM
FF3355113377u
MM
FF3355113333~
FF
Tae 3 Table I
Comes iris Costectiwe Individual Eye Irritation Scores
& Cornea g
~
~
LIrCeis
2Con.junctivae
~
~
~
I Hour
0 0
0 0
yIi
22b
1 1
22:
0 0
0 0
EIid
32b
22
11c
0 0
0 0
1Ii
22b
22
I:
TewTSScocootrareel r"
1155 1155 1155
24s 24 Hours
Mean
15.0
FF3355113366
MM
0
00
00
FF3355113377
MM
o0
0 0
00
FF3355113333
FF
00
0 0
00
2 2
i 1
1
88
22~
i 1
22~
1100
22b
00
r]c
66
a sours 48 Hours
Mean
8.0
Boor o8 FF3355113366
"M
00
F3355113377
"M
00
F35133
F
0
oars Cornea 3 ures of ommetty A - Degree of opacity
00
00
00
00
8 0 fn 0
0
22
1I
z2
1I
I
0
" onContinciiae Iris GC -Oagree of rida D - Basness Degree of iridal
22:
I100
22~
1100
0
2
Mean
7.3
Con.iunctivae
D Redness
B - Area of involvement
irritation
E Chemosis F Discharge
R LEEarse "Ce: ( (A x BA x 5)+x + ((CCxB x85)) ++x ((DD+5 EE F+ )F) )xx22.
b - Blanching.
= Clear discharge.
~ Injected iris.
~ No pain response after test material instillation.
~ - Excessive pawing at the treated eye after test material instillation.
n~te d
Kin ~ d o m
Fax
608-241-7227
--_---------------- 3M MN01241257
22778877..00000077
: Niscons Ly WISCONSIN
-
NE 330' SURELY ( '-.SM~,N
HHUWTI NNuummbbeerr:: 0011110044113988 SSaammppllee:: TT-55229988
+CORNING iranSc amar
PPaaggee 88
AnAtiunsmimbaealrl Number 3F33555111333676 FF333555111333373 F333555111333687 35133 F35137 F35133 F333555111333765 3F355113337 F35133 F333555111333756 F3355113337 F35133
IndividTTuaaabbllleeEy11e ((ICCroornnitttiianntuuieeoddn)) Scores
Individual Eye Irritation Scores
sex
CB oCronrneB eaa L. IIrriiss
conjunctiva RD Con.iunctivae E
TToottaall score
Sex
~
B
C
ScorR*
7122 HHoouurrss
HnM
o o 0 o o0
000
222 111
011C
868
fFMF
[002
o 0
00 0
[20I
1 0
o
00 6
MMeeaann
a4.77
9H9266ouHrousr.s
nM "
o o0 o00
0 00
222 I11
0I1C
868
MFF
00oo00
0 0
o 02 o0I
0
60
MMeeaann
a4.77
fDaayv?7
HuM
0[0I 00
000
11 10 00
000
222
FM
F
o 00 o00
o0 0
0o 1 o00
0 0
0 2
HMeeaann
11.33
DDaayy114
HHM
000 000
e 0 o00
0o0
0 00
FM
F
[0o2
0 o
0
0
0 0
0 0
0 o
0 0
Mean
Mean
00..00
CCoorrnneeaa AA8 --- DADereeggarreeeeofooffinoovppoaalccviiettnyyent
B Area of involvement
IrIriiss CC -- DDeeggTrrreereeitaootffioiinrriiddaall
irritation
-S+a: C( (lAeaxrBA dixsc5)h+ax r+g(e(.CC xB x55))++x ((OD++5 EE F+FF) )) Xx22.
c - Clear discharge.
CCoonnjjuunnccttiivvaaee 0D -=- cRReheddennneeosssssis EFF -- DCDihiessmccohhsaairrsggee
Phone
Un~tel Kingdom Fax 608-241-7227
--
22778877..00000088
wom 3M MN01241258
~
2
WISCONSIN WISCONSIN Wee ~05 ~=,~ 8~
HHWWII NNuummbbeer:r' 0011110044119988 SSaammppllee:" TT--55229088
conn con
PPaaggee 99
anime) Animal Ter Number F518 F35135 BEY F35137 Fa F35133 NEG - Ho NEG - No
TTaabbllee 22
Sodium Fluorescatn Examination Sodium Fluorescein Examination
goseryation perios Observation Period
Prem ee eT Preinitiation
72 Hour
Day 7
nes wows NEG
NEG
NEG
NEE NE one NEG
NEG
NEG
NEE ME ME NEG
NEG
NEG
stain retention. stain retention.
Tarn Day 14 nesNEG neNEG NeNEG
: orscussion DISCUSSION The test material, T-5298, when evaluated for its primary eye irritation The test material, T-5298, when evaluated for its primary eye irritation potential in rabbit produced ids] invalvenent and moderace conjunctival potential in rabbits, produced iridal involvement and moderate conjunctival Boration." KIT eye Eai returned to a normal appearance by Day 14 after irritation. All eyes had returned to a normal appearance by Day 14 ater treatment treatment.
RereRences REFERENCES 1. "Acute ye Irritation Corrosicn, organisation for EconomicConger on "Acute Eye Irritation/Corrosion," Organisation for Economic Cooperation
and Developmen3t Gurded nes for Testing of Cremieals. Section 405 and Development's Guidelines for Testing of Chemicals, Section 405 {adapta Hoy 12, 1561) (adopted May 12, 1981). 2. NIH Publication No. 86.23 (revised 1985) NIH Publication No. 86-23 (revised 1985). 3. Dratze, J. H., "Gye Mucosa," In Appraisal of the Safety of Chemicals in Draize, J. H., "Eye Mucosa," In: Appraisal of the Safety of Chemicals in Foods: Orica ind Fasnetres Oeraal Toxicity. Aisociar on of food and Oey Foods, Drugs and Cosmetics - Dermal Toxicity, Association of Food and Drug
O Offffiicciiaallss ooff tthhee UU..SS..,, pppp.. 4499--5500 ((11997755)}.
--_--
Phone 608-~41-~471
22778877..00000099
Fa~ 608-24t-7227
ww 3M MN01241259