Document 3p9kQKg3LrxEbjZJMMmJOp0O
ENCoomioogm n.weto5n370t7c7545
+ Dlr 1100 Kan Bods Madion, 1 5374 608.241.4471 608.241.7F2a2x7
Sponsor:
mn St. Paul, Minnesota
AR116-_ 0U27
`CORNINGHazleton
ECE
1 0CT 30 1995
Ray "gon
FINAL REPORT
Study Title:
Acute Dermal Toxicity Study of T-6342 in Rabbits (OECD Guidelines)
Author:
Steven M. Glaza
StudyCompletionDate:
October 24, 1995
Perforning Laboratory:
Corning Hazleton Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704
aboratory Project Identification:
HHI 50800374
Page 1 of 32
00114
Page 2 of 32
HHI 50800374
COMPLIANCE STATEMENT
Acute
Dermal
Toxicity (OECD
GSutiuddeylionfesT)-6342
in
Rabbits
CThoiospersattuidoyn waasndcoDnedveulcotpemdenitn'sacPcroirndcainpcleeswitohf
the Organization for Economic Good Laboratory Practice,
(81)30(Final).
Steven M. Glaza Study Director Acute Studies Corning Hazleton Inc.
Date 0WAS
00115
.
Page 3 of 32
HHT 50800374
QUALITY ASSURANCE STATEMENT
WTihsicsonrseipno,rtIhnca.s, beiennacrceovrideawnecdebwyitthhetQheuaOlrigtayniAssasturiaonnceforUniEtconoofmiHcazleton
CPoroapcetircaet,ionC(8a1n)d30D(eFvienlaolp)m.entThe(OfECoDl)lowPirnignciipnlsepsectoifonGsoodwerLeabocroandtuocrtyed and
rfeipnodritnsgsofrepionrstpeedctitoonstheandStufdiyndDinigrsectaorer monthly according to standard operating
ainsdsumeadnatgoemHeanztl.etonWrimtatneangemsetnattus procedures.
FIrnsopnection TDaotes
Phase
RepoDratteed to Date to Study Director Management
1008//1331//9955 0180//3116//3955 DDoastea/ARdempionritstRreavtiieown
1008//1361//9955 0191//1100//3955
Representatifie, Quality Assurance Unit Date lo 24 15"
00116
Page 4 of 32
HHT 50800374
STUDY IDENTIFICATION Acute Dermal Tox(iOcEiCtDy GSutiuddeylionfesT)-6342 in Rabbits
Test Material Sponsor
Sponsor's Representative
Study Director Study Location StSutdyudyTimIentiatbilaetion Date
EIxnp-elriifmeenEtnadl Da(tIen-1ife) Start Date SEtxupdeyrimCeonmtpalletiToenrmDiantaetion Date
T-6342 TEloxicology Service 3MMeCdeintcearl, DeBlpdagr.tme2n2t0-26-02 SP.t0..PaBuolx, 3M3N22055133-3220 MRHoger G. Perkins, PhD ToMxeidcioclaolgyDeSpearrvtimceent 3PM.0.CenBtoexr,332B2l0dg. 20-26-02 S(t6.12)pau7l3,3-3MN222 55133-3220 SCtoervneinngM.HazGlleatzoan Inc. MPa.0d.isoBno,x W7I54553707-7545 (608) 241-7292 C33o0r1ninKginsHnaaznletBoonuleIvnac.rd Madison, WI 53704
AAuugguusstt 3215,, 11999955 OScetpotbeemrber24,14,19915995 October 24, 1995
C0117
i
Page of 32
HWI 50800374
Acute Studies
Steven M. Glaza Study Director Manager
SSttuedvyenCoR.ordSionraetnosron
Patricia Padgham In-1ife Supervisor Rose M. Bridge Report Supervisor
Toxicology Support Kathy Myers
Manager
CSaulpveirnvisL.orHorton
uality Assurance
MSahneargreyrR. W. Petsel
KEY PERSONNEL
LaborAnianaltMoedirciyne
Cindy J. Cary, DVM Diplomate, ACLAM Supervisor
AnatonicalPathology
Thomas E. Palmer, PhD Anatomical Pathologist Deborah L. Pirkel/
JSNaeuccpkreorpvSsieysrofrosrt Supervisor Anne Mosher
Pathology Data
00118
Page 6 of 32
CONTENTS
QCounagliftayncAessuSrtaantceemenSttatement KSetyudyPerIsdoennnteilfication ObSjumemcatriyve TTeesstt SMaytsetreimal RPreoscueldtusres SDiisgcnuastsuiroen RePfatehroelnocgeys Report
Tab1 leMortality Summary
32 IInnddiivviidduuaall CalnidniMceaaln BSiogdnysWeights/Body Weight Gains (g)
4 5
IInnddiivviidduuaall DPeartmhaollogIyrrCiotmamteinotnsObservations
APprpeontdoicxolA PPrroottooccooll AAmmeennddmmeenntt NNoo.. 21
HHI 50800374
Page 2 43 75 77 58 10 111 112
13 115 1186 2109 3321
00119
Page 7 of 32
HN 50800374
SUMMARY
Tpahopetpelnittceiasattliomnaitneatmriaalale,TeavnTed-l63f4oe2fm,al2we,a0s0r0abembvgiat/lskugawtheoedfnbfooadrdymiiwntesiisgtahectru.etde
daesrmaalsintgolxeicittopyical The estimated dermal
Log; for male
2,800 mg/kg.
and
All
faenmiamlaelsraabpbpietasrewdasnodremtaelrmtihnreodugthooubte
exhibited body weight gain during the study with the
greater than etxhecepsttiuodyn. ofAlolne
amnailmeals
wmtahetirecmrhiinaaeltxihoipnbriotdreuedcveedaalewsdeliiggnhohttvit1so0i5sbmloedoefrlae2ts9eigondsed.rumrailng itrhreitaftiirosnt.weeTkh.e grTohsestensetcropsy at
OBJECTIVE
Tshkein obijrercittiavnecy ooff tha istessttudmyatewraisaltowhaesnsesasppltiheed styostetmheic sktionxiocfityrababnidtsr.e]ative
AAcTt did
Rnpoertgouclueandtunireoecnsess.suasreidIlnyintdheutphloiispcianstiteoundyanoyfweprterheeviiSnopuocsnosmowprolrikaa.nndceswtiutdhy
dtihreecAtnoirm.al thWeelfsatruedy
TEST MATERIAL Identification
TTihqeuitde.st material was identified as T-6342 and described as a clear, colorless
Purity and Stability T(hienclSupdoinnsgorunadsesrumetsestrecsopnodnistiiboinlsi)t.y for purity and stability determinations
StoanrdReategntieon
Twihlel tbeestrmeattuerrnieadl twoasthestSopreodnsoatr arfotoemrteimspseuraantcuereo.f thAenyfiunnaulsedreptoerstt to Corning Hazleton (CHH) Standard Operating Procedure (SOP).
maactceorridailng
SafetyPrecautions
The test material handling procedures were according to CHH SOPs and policies.
600120
Page 8 of 32
HWI 50800374
Test Animal
TEST SYSTEM
Adult albino rabbits of theHra: (NZW)SPF Kalamazoo, Michigan on August 9, 1995.
strain were procured from HRP,
Inc.,
Housing
After receipt, the During acclimation
animals were acclimated for a and throughout the study, the
period of at animals were
least 7 days. individually
housed animal
in screen-bottom room were set to
stainless steel cages. maintain a temperature
Environmental controls for of 19 to 23C, a relative
the
humidity of cases where
50% +20%, and a variations from
12-hour Tight/12-hour dark Tighting these conditions existed, they were
cycle. In documented
and
considered to have had no adverse effect on the study outcome.
Anima) Diet
The animals were provided Laboratory Rabbit Diet HF
access #5326,
to water ad libitum and a PMI Feeds, Inc. The feed
measured amount is routinely
of
caonnatlaymziendanbtys.theSammapnluefsactoufretrhe fworatenrutrairteiopnearliodciocmaplolnyentasnalayndzedenbvyiroCHnWm.entaTlhere
wienrteerfnoerekdnowwnithcoonrtamaifnfaencttsed inthetheresfueletds orofwathteerstautdyl.evels that would have
Animal Selection and Preparation of Exposure Area
Five male and five female healthy, acclimated rabbits, weighing from 2,386 to
a2n,i6m7a5lsg, wewreere iduseendtiffioerd abysianngilmealdosneumbleervelandofco2,r0r0e0spomngd/kigngoefarbodtyagwetihgrhotu.ghouTthe
the study. On the day before test material application, each rabbit's back
was not
clipped free of hair less than 10% of the
with an electric clipper. The clipped area made total body surface. The animals were clipped as
up
needed throughout the study.
ustification for Species Selection
Historically, the choice because of
New the
Zealand White albino rabbit has been the animal of large amount of background information on this species.
000121
Page 9 of 32
HHI 50800374
PROCEDURES
PrepaofrTeasttMaiteorinal
tcTeahsletcutlaeadsttmeidnmiastatenrrdaitawileoingw.haesdaodumtinibsasteedredonaseacrheceainviemda.l'sAnbodiyndwieviigduhatlondostehewadsay of
Ireatment
tdThoheseetteeTssettvelmsaitoteefria2at,l00a0warsantg/eakpgopflioefadpbportdooyxitwmheaeitgeihlntyt.ac0t.0T3hsekig/ntcenso'tn
meaatcehriaanlimwaals's apbpa]cikedat toa in a thin and uniforn
w9lia.ty5he-rc.SmarxaTnh2e1W.0ra-arcpema, ao4nfd-palEpylpalsigactuaoztpeiloanpsatt(cahtpappsreeocxtuiormeadptrewolivytihd2e00paanpcne'rocJctwlaapusesicvaoenvdedrroeevdsesrwiwnirgta.hppaed
pCeorliloadr.s were used to restrain the test animals during the 24-hour exposure
bAtandtahgeesendweroef rtheemov2e4d-hoaundr disposable paper towels.
tehxepostuerset
spietreisod,wertehewarsehsetdraiunsiinngg
tcaopllwaartserandand
Reason for Route of Administration
Historically, the dermal
method of Draize.?
route
has
been
the
route
of
choice
based
on
the
Observations
o2Cb.l5si,enircvaaanltdioo4nbssheourarvnsdatiatowfnitsceeranatdedstamyomramttoaerlrtiiatalylitcyhaedccmkhisencikswsterrae(tmicooronnn.idnugcAtdeaddnidtaitaofntaaeplrpnroocoxlnii)nmiacwtaeelrley 1, conducted daily thereafter for 14 days.
DBaoydy7,weiagnhdtsatwetreermidneatteiromnineodf btheeforien-Ttiefset pmahtaesreia(lDayapp14l)i.cation (Day 0), at
rTehmeovianlitioafl thdeermtaelst imrartietraitailonacrceoardidnigngwatso the Day 1 score). Subsequent readings of
mtahdeeDraapipzreoxitmeacthenliyque30 (mriencuotredsed afaster dermal irritation were made on
Days 3, 7, 10, and 14.
600122
Page 10 of 32
HHI 50800374
Pathology
rAaentcoatrbedbrermdei.vniaattAiefodtnergorfonsetschreonpeiscnyr-,olpisftyheeepxahaanmsiein,naaitsailolwne,raeniamdnadilsscaanyrwdeeradebnoaernudmtahlanoinitziteeidss,suweessruebwjeerceted to saved.
Statistical Analyses No statistical analyses were required by the protocol.
Location of Raw Data, Records. and Final Report rTheetairnaewddaitna,therecaorrcdhsi,vesandofaCnHHoriigninaaclcorsdiagnnceed wciotphy CoHfWthSOeP.final report will be
Mortality
RESULTS
dAursiunmgartyheofstutdhye. determined to be
surThveivaelstirmaatteedisdeirnmaTlablLDe,, 1.forNomamloertaanlditfyemwaalse greater than 2,000 mg/kg oF body weight.
orbasbebrivtesd
was
Body Weights oaInnneidmiamvlaisldueaelwxhhiiacbnhditeemdexahnibboidbtyoeddwyeiwagewhiegtihgtgshatinanldtoshsrbooudogyfho2wu9etigghttdhuergiasnitgnusdythaewrietFhiirnstthTeawbeleeexkc.e2.ptioAnll of
Clinical Signs tIhnrdoiuvgihdouuatl. ctlhienisctauldy.signs are in Table 3. AI aninals appeared normal
DermalReactions
o(Ifbnadsisevldiidguhoatnl ttohdeemrmomadolesrtaitrserevieetrrayettihosencmoaro,ebseefdroervmaate,iaocnhasndanairametaolniinaa,tTabaanlndey
t4.imeDepromianlt) icrornistiasttieodn slight desquanation,
coriaceousness, and fissuring. No other dermal irritation Was observed.
00123
Page 11 of 32
HUI 50800374
Pathology
bIyndtihveidusatludygropsasthonleocgriosptsyispatonholPoaggye observed at necropsy.
f12i.ndinTghserearweerien
nToablveisi5.bleAlessuimomnasry
report
DISCUSSION btThohedeynawaceduitmgeihntid.sertmearTlehdeteoassxtiicamiatstyiendgolfedeTrt-mo6ap3li4c2aLlwDa,sapfpeolvriaclmauataliteoendanaidtn fmaeamllaeelveealnrdaobffbeim2ta,sl0e0w0arsmagb/bkigtsof wdtiehttrheorumgtihhneoeudtexcttehoeptbiesotnugdryoe.fateonArleltmhaaalnneim2wa,hl0si0c0henxdeh/xikhbgii.tbeidteAdlblodayawnewiiemgiahglthst lagopaspsienarodefudr2in9noggrmadtluhreinsgtudy ithreritfaitrisotn.weekT.he gTrhoesstesntecrmoaptseryiaalt tperromdiuncaetdiosnligrhetveatloedmodnoeravtiesibdleremal]esions.
SIGNATURE
SSttuedvyenDHi.recGtloarza Acute Studies
Date 104
REFERENCES
1.
D"eAcvuetleopDemremn'alts GTuoixdieciltiyn,e"s May 12, 1381).
OforrganTiessattiingonoffoCrhEemciocnaolmsi,c
CSeocotpieornati4o02n
a(naddopted
2. TDoforxaiitczhieet,yS,aJ.fAestHsy.,ocoif"aAtCcihuoetnemicoDfearlmsFaoloidnToaFnoxdoidcsiD,rtuygDr(uOSgfisfnigclaienadlEsCxopsoofmseutrtihece)s,"U.-SI.Dn,:ermpapA.lppr5a4i-s5a6l (1959).
600122
Page 12 of 32
HWI 50800374
PATHOLOGY REPORT
There were 10 rabbits at the termination of
(five males the study.
and The
five dose
females) euthanized andnecropsied level, day of death, and gross
observations recorded for that follow this report.
each animal are in the Individual Pathology There were no visible lesions in any of the
Comments animals.
oi Eo Patter
Pathologist (50800374. rpt) 092695
2 tate-24-75
00125
Dose Level
--{ma/ka)
2,2,000000
Page 13 of 32
HI 50800374
Table 1
Mortality Summary
Mortality Result
Sex
NoD . ieNod .Do/ sed
FM
oo//5s
00126
Page 14 of 32
HHI 50800374
Table 2 Individual and Mean Body Weights/Body Weight Gains (g)
Animal
Number
FF5566227611 5566226665 FS6267
Mean
Dayo
Weight
22,,458513 22,,359216 2,529 2,496
Dayz
Weight Gain*
Males(2,000ma/ka)
22,,55622 2891
22,,537973
512
2,613 84
2,53
38
Day 14
Weight Gain*
22,,568022 10819 22,,478007 18819 2,714 185 2,625 129
Females (2,000 na/kg
5FS66226698 F56264
22,,454384 22,,468885 2,386 2,512
13516 126
22,,757505 2,536
120376 150
FFsS66227740 22,,468775 22,,562719 344 22,,658842
959
Mean 2,506 2,576 70 2,625 19
* Gain from the Day 0 body weight.
600127
AMentetr goaervation FS6281 Appeared normal 6271 Appeared normal FS626S Aopearednormal FS8288 sgpearadnormal FS5287 Appeared normal
36268 Appearednormal 36263 Appeared normal Fs6z6a Appearednormal FSEET0. Appeared norms] F624 Appeared norma) 7 condition existed
Pa15gofe32
HHI 50800374
Tabl3e Individual Clinica signs Dswour WIz3f +oy If 80f EElE tales 2,000sojka) Clitrs ss Citr i r Clit sry Cts irs Clit ir s femles (2.000safio) Cts rir Clit irs Citr i ss Clits sissy Cll tris
600128
Page 16 of 32
HWI 50800374
ANnuimmbaelr
F56261 F56271 F56265 F56266 F56267
Table 4 Individual Dermal Irritation Observations
Observati. on
I OibservatiFonrPeriodn (Day; =
Males
Atonia 1 0 0 0 0 Erythema Edema
1
1
1
1
1
1
I]
0
0
0
Desquamation
0
Coriaceousness
0
0 0
0 0
1 0
0 0
Fissuring
0
0
1
0
J
Coriaceousness 0 0 0 0 0 Erythema
Edema Atonia Desquamation
Fissuring
1
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
[J
0
0
0
J
0
0
Erythema
1
1
0
0
0
Edema 1 0 0 0 0 Atonia
Desquamation
1
0
0
0
0
0
0
[1
0
0
Fissuring 0 0 0 0 Coriaceousness
0
[J
0
0
0
Erythema Edema
1
i
2
1
1
1
0
0
0
0
Atonia
0
0
0
0
DeFCiossrqstuuaarcmieanotguisonness 00 000 000 001 000
Erythema Edema
1
0
0
0
0
0
0
0
0
0
Atonia Desquamation
1
I
0
0
0
0
0
0
0
0
Coriaceousness
[
0
0
[
0
Fissuring
0
0
0
0
0
* Animals shaved before dermal observation.
00129
Page 17 of 32
HH 50800374
Table 4 (Continued) Individual Dermal Irritation Observations
Anluimmbaelr Observation
F56268 F56269 FS6264 56270 FS6274
EdEreyntahema DAetsoqnuiaanation FCiosrsiuarcienogusness
EdEreyntahema AtDeosnqiuaanat ion FCiosrsiuarcienogusness EdEreyntahema AtDeosnqiuaanat ion FCiosrsiuarcienogusness EdEreyntahema AtDeosnqiuaanat ion FiCsosriuarcienogusness EdEerymtahema ADetsoqnuiaanation FiCsorsiuarcienogusness
I O3bservatironrPeriodnn(Day =
Females
11 1
011
021
021
01 0
00 0
00 0
01 1
01 1
01 0
11 2
22 1
22 0
22 0
021
00 0
00 0
001
01 1
01
11 0
01 0
01 0
00 0
00 0
00 00 00 00 00
00000
11 0
22 0
22 0
021
11 0
00 0
00 0
001
01 1
01 0
01 11 21 11 00 00 00 00 01 00 00 00 1 0 00
* Animals shaved before dermal observation.
600130
Page 18 of 32
Table 5 Individual Pathology Comments Dose Level: 2,000 mg/kg of Body Weight
Animal
_T ___ es Dayt
F56261 M -
Fs6271 M -
F56265 H -
F56266 M -
F56267 " -
F56268 F -
F56269 F
-
F56264 F -
F56270 F
-
Fs6274
F
-
1
No visible Tesions.
1
No visible lesions.
1
No visible Tesions.
1
No visible lesions.
14
No visible lesions.
1
No visible lesions.
un
No visible Tesions.
1
No visible Tesions.
1
No visible Tesions.
14
No visible lesions.
- Not applicable.
HHI 50800374
600131
Page 19 of 32
APPENDIX A Protocol PArmoetnocdomlent No. 1 Protocol Amendment No. 2
HW 50800374
00132
Page 20 of 32
SZThuialsafmotrepsmtilingte.obSSouupsbedemwihctantisnaueblaemdistFlicnoaglnsrbaemamepalsselsyfioarmriaonutggiendg.~~ HEHanWzcIllSoottsoeundwWiyithsNocs.oanm_palnsesaondssoeoizry ") 22b44y11c-7o4n24t71a10c,tiEnxgtth7e29A2c.uotreTtohxeiGceolnotgySDeerpviacretmCenet anfa(t6t(0680)r8) M3a3d0i1soKni,nsWmiascnoBnosuilnev5a3r7d04
orn `Submitted by:
Las
Date Sample Sent:
Tr
PO.Number 0
Full GLP Compliance: _--XN_oY'es __EP_ AF(oT_S(2C1AG--F4R058C)FR 792)
Numberor Reports Required: 3
X--C OErPAch(FIFRA--40 CFR 160)
Sample Name:Tea0
SPpheycsiiaclalHDaensdcirinpgtiPornocavions: _L_gSEEM70STD-S[79085 Lfatned
Lte0084 uparddown L050 proce ri Same Storage Requirements: --_X. pReokoimgerTaetmopgerature ----Oher
Disposal: _ XK DRispoosteoofsu aucbmcim otredrintgo
Hazleton SOPs.
Tests
Primary Skkiin n IrIrrrititation
foute Oral Toxicity in Rats
--TP3208 FHSA 6 abbis-1 abraded, 1 intact strabbit
--TPT3P2001741 EPOAEC;D:6 r3arbabbitbsi-s1-initnatcatcstitea/rabbit
--------TT= PP3a0210C38onEdFuPHcAStAsdcesrfceirenenee:dn:SsMSt-uSdSyFiFfaa1dte5.a05gt0hio9gc4cgurs ai 5.0 ghg ZT--PT145 Photpotorxicoty.pa raAbbyits2. ntsaucrtes)itesirabbit
`Special instructions.
`
--ATP20C6o9ndOuEcCtDdesfcirneeedn:stSuMdy.ifSadFeat5.hoo0ckcuors a509kg -
oi
i
i
Sell Conductdefinedstudy if deathoccursat 5.0gg -
Ae ects sinietons: m i sA Primary EyT e IrritO ationprocuenduwraes;h6erdabbis unwashed
----TuTPtRAe302D10e67rmEFaPlHAATsocsxrcierceenie;tn;ySWSi.Mn5SFRFaaab12b1.i02gt0shgk
P2012 1978 EPA;6 rabbits orwashed,3 washed S--X-TTPP23007125 O1E98C2D:EP3A;ra6briavbsbiutrsmausnhweadshed
XTTPTR2ao0s7G0 uGaEGogesicnreeednsstSuWd.y5iFdde8ea1att2hh0goccgurocsursa422004 Spec--alns33ianacbtb-- aoinss:wwaaosnhaegd aat 04 so*ecoonnds,
eeckeAnas oniuct _-- ---- r definedstudy death occurs at 2.0gkg
EE
For Hazleton Uss Only
Protocol Issue Pre
X ESAs
ty Dict; ___ Nae
%
White copy--Hazieton Yellowcopy--Submitter
--G--uiPn2e0aP161P76i4 gOEEPSeACnDMsaiMgtanigzunasutssiosonunnK-iKgimgamnanmamsaixniizmagtaotnon
S--5p5Te2cPi1a27l50n20s8i89ncPBrhuioerlheolrselrlesreogneosniiiczcaotnitonact
_--
dermatiis
(ATramsrtrronag)
-_--m
00133
@HAZLETON
HS LONSIN
Page 21 of 32
Soonsor:
3M St. Paul, Minnesota
PROTOCOL TP2070
Study Tite: Acute Dermal Toxicity Study in Rabbits
(OECD Guidelines)
Date:
June 1, 1993
Perforning Laboratory:
Hazleton Wisconsin, Inc.
Ma3d3i0s1onK,inWsimsacnonBsoiunlev5a3r7d04
Laboprorjecat Idtentioficratiyon: Wl _sopocary
for ve --t ow sn nonin wenn el 0 0001348
Page 22 of 32
PPa2g0e702
STUDY IDENTIFICATION Acute Derma(lOETCoDxiGcuiitdyelSitnuedsy) in Rabbits
HI No. Test Material Sponsor
Sponsors Representative
Study Director
Study Location
PrEoxppoesreidneSnttuadly Experimental
STtiamrettabDlatee Termination
Date
Final Report Date
sO8oS37y (See sample submittal form) Tmowxicology Services 2St2.0-2Pau-l0,2 M3NM C5e5n1t4e4r ohn L. utenhot, pho ST2t2o.0x0i-Pc2ao6ul-lo0,g7yH3NSeCre5v5ni1ct4ee4sr (612) 733-1962 HPS.at0ze.lveetnBoonxH.W75iG4sl5ca.oznasin, Inc. M(a6d0i8)son2,41-W7I207537077545 HBuaizlldeitnogn WNoi.sco3nsin, Inc. H3a8d0i2soPna,ckWeIrs A53v7e0n4ue
WWeecekk ooff 38..1281.9955
Weekof/o-23-95"
060135
Page 23 of 32
TP2070 Page 3
1. Study Acute Dermal Toxicity Study in Rabbits (OECD Guidelines)
2. Purpose To assess the test material
wshyesntemaipcpliteodxictoitytheandskirneloaftivreabbsiktisn
irritancy
of
a
3. BeaulatoryCompliance This study Laboratory
PwirlalctibceeRceognudluacttieodnsi/nStaacncdoarrddasn/cGeuiwdietlh
the following ines:
Good
[12 [] Conduct as a MNonregulated Study
1 CR 58 (FoAy [ ] 40 CFR 160 (EPA-FIFRA)
[] 40 CFR 792 (EPA-TSCA)
[]
C(81)30 (Final) Notification No.
(OECD) 3850,
August
[1 No
10,
1984 (Japanesenner)
Nottiiffiiccaattiioonn NNoo.. 837103,, OMacrtcohber31,5, 1918928,8 (anJdapaasnesaemeMnOdHed)oy
WAe]lfaprreocAecdtureRseguilnattihoinss.protIoncotlhe aorepiniinoncoomfplitahenceSpownisth theAnimal
director, work.
the
study
does
not
unnecessarily
duplicate
or and study any previous
4. Quality Assurance For regulated studies, report will be audited
btyhethperotQoucaolli,tysAtsusduyracnocneducUtn,it and
thefinal
with Hazleton and policies.
Wisconsin
(HMI)
Standard
Operating
in accordance Procedures (soPs)
5. TA.estIMdaetnteirfiiaclation (See sample submittal form)
8. PhysicalDescriotion (See sample submittal form)
C. PuarndiStatbiliyty deThteerSmpionnastoironasssu(miens.clurdeisnpgonsunidbeirlitteystfocronpduirtiitoynsa)n.d
stability Sample
ctoenstcenmtartaetriioanl,/veshoilucblielimtiyx,turheo(mso)gen(eiiftya,pplanidcabsltea)bilfiotry s of
will be Sponsor.
taken before administration if These samples (if taken) will
requested by be sent to
analyses the
after experimental
termination
for possible
the Sponsor analysis.
000136
Page 24 of 32
PPa2g0e704
0. S(tSoeeragseample submittal form) E. RePhsauvederiveresesSeoarfmvpelleessssamptlheasn r4etwaeienkesd.in experimental duration will not
dTtuaarkgaeetnrivoeInF.stahmilse(sst)udyofiseancohrebatthcahn/l4otweoefkstesint meaxtpeerrfiamlintw.i]ll be
BTJeehrsesIitMeeIrst$sem0tatetoriTamhlaeinSrtpeaosinensrovrea fiaposition, In accordance
itselammlppleebreawtciulorlnetaobcfetebsdteolarofetde0rat with
fIoIr 1ipn 14 vecs'
Saears Sor
Laboratory Practices.
the appropriate. reguietems acn
F. HRtheyetenufitnnuiasolendretpeosrtt,matuenrlieasls dwiilrle;ctbeeddoitshcearrdweidseabfyterthefsSseuoannccoer"of G. SaAsferteyqPurierecdaubtyioHnHsI SOPs andpolicies 6. ExperimentalDesign A. nmals
(1) Rsapbebciites
(2) SHrtar:ai(nN/ZSNo)uSrPcFe/Hazeton Research Products, Inc. (3) AAgaeuttat Initiation
(4) M2e.i0gtht03a.t0Iknyitiation (5) N$(iumfmmaabllreeeerssquaiaanrndneddd/s)oerxfsemafleemsalefsorftorheaniynitaidadlitidoonsse] Tdeovcele Tevels
(6) dIendnitviifdiucaaltinounnbered ear tag
00137
Page 25 of 32
PPa2g0e705
(7) Husbandry
(@)
H{onudsiivnidgually,
(heavy gauge]
in screen-bottom stainless steel cages
(b)
fF{opomuorediansaurMeidllasm,ounItnc.o)f. HigThheFifbooedr by the manufacturer for n
RiasbbriotutiCnheolwy
a5n3a2l6yzed
environmental contaminantsu.tritional components any
(c)
MJdatelribitum fron an phaartdenresasr,e aannalyzed
bayutIoNmIatifcor styosttaelm. disSsaomlpvleeds
sooflitdhee,
ofrogransceplheocstpehdadteelssep,neecnaintfdsi',ecdhhlemoairvciyrnoabmteietoadllosgh,iycdraolcacrobnotnesn.t ang
(4) CTthohenartteawmoiaunrlaedntnosintkenrofwenrecownittahmintahnistsstfundyt.he food or water
(e) EsEenntvviitrrooonnmmmeaenintntatlainconatrtoelmsperfaotrurteheofan1i9maltor2o3o-mc,wilal be
rTeilgahtti/v1e2-hhouunriddiatrykocfyc5l0e%. 120%, and a 12-hour
(f) AAtcclTiemasattio7ndays
(8) S Banodaese aqenudial mtoaenleonRuiefnmacTbTeotebrt hsvtioai ofnAudnseiolxbmytoardnlapyosoawrneiimghaheltasltahwcicloilsrdbipenlgacpeutdrocohHnaMsIedSOPvos..thaAyn fuss.
(9) JHthiesutoarnsiicnaatlllyio,fffc"othhroieiScNpceeewcbiaZeeecsaatSuTsaeeinldeocofWthiitnothene alalrbgienoamroaubnbtitofhas been background information on this species.
8. Dose Administration
(1)
DAadomssieinnigslLeetveelrdeodsetoofth2e,00i0ntamcgt/kgskionf females. If 10 tes
boofdyfivweeimgahlteswilalndbeFive
prerqoudiurceedd.
at
IFthaisny
lmevoterltm,aaltientroyiafoluc-rcrtuehrelsrateattdesttmhioenrgt2aw,li0il0t}0y
biys mg/kg
00138
Page 26 of 32
TP2070 Page 6
level, additional dose
abject ves of the stu direction of the study
dlierveecltsormayin beordaedrdedtoat the
dy. meet the
(2) CPreepra.ratioNnotof Exposure Area Oeanchthreabdbaiyt bweiflolrebetecsltipmpaetderifarlee aopfplihcaaitrion, the back of Tess than 10% o with an electric
throughout the study. f the tora) body sreiciric, will be clipped. The animals will be clipped as needed
(3) Dose Adninistration Uithupaper tape around all edges, overwrapped with Sevan ATT animals will receive mweaitgehrtialj.ust Thbeefdoroese will
a single be based
administration oftest upon the animal's body
The area uniform
of
applicataidomninwiisltlratbieoncovoefretdhewittehst asmattehriinala.nd
mmaatteerriiaall awillalyerbe asappploisesdibluen.dilIuftead.liquIifd,a
the test solid, the
tes
materials
will will
bebe mdoiissctheanregdedwitihnto0.a9%besaaklienre.and Aerosol
t
wardanpipneidstewrietdh aas 10a.0l-iqcumidx. 10.T0he-cmaregaauzoef baapnpdlaigceatisoencurweildl be
Wrap, and
the 24-hour applica occlusive
dsreecsusirnegd. witThheElraasbtboiptlsastwilltabpee
to provide collared
an
tion per od during
(4) Reason forRoute of Adninistrat.ion Hcihsotiocreicbaalsleyd, onthethedemrmeatlhodrooufteDrhaaiszeb.een the route of
(5) Removal of Test Material
test material will be renoved Atpheprboaxnidmaagteeslyan2d4 choolulrasrsafwtielrl tbeestrmemaotveerdi,al anadpptlhiecatrieosni,dual C. ObservoafAtniimoans using water orca. appropriate solvent, ifnecessary.
(2) Reading ofDermalIrritation (1) Clinical Observations
At approximately 1, administration for
2.5, and clinical
4 hours signs and
after testmaterial mortality,
thereafter for clinical p.m.) for mortality for
astignlse,astand14 tdwaiycse. daOiblsyer(vada.atmi.lyand
may
be
extended
when
directed
by
the
study
ions director.
Aipnpitrioaxlimadetremlayl 30irmriintuatteison arfetaedrinbganwdialgle breemmoavadle, antdhe
00139
Page 27 of 32
Tp2070 Page 7
greercmoarldedirarsitatthieonDayrea1dirnegasdiwnigll(Abtetamcahdmeenotn 1S).tudyAddDiatyison3a,l
7, be
10, and 14. Individual dermal maintained for each animal.
irritation
records will
(3) Body Weights Janudstatbedfeoarteh te(swthenmatseurrivailvalappelxicceaetdison1, daoyn) Days 7 and 14,
pecropsy examination and all abnormal ties wii) pe rarecsoy' D. Pathology
Awitlltebremienuatthiaonnizoefd.theAlelxpearniimmaelnst,al whpehtahsee,r
surviving animals dying during
study
or
euthanized,
will
be
subjected
to
an
the abbreviated gross
After necropsy, will be saved.
the
animals
will
be
discarded
and
no
tissues
E. StanaatliysstesicaarleAnfaelquyisreesd. Other than LD, calculations (when applicable) no statistical
7. Report A final report including those items Tisted below will be submitted:
Description Description
of of
the the
test material test system
Procedures DTaatbeuslatoifonexpoefrimmoernttaallityindiattiaatiboyn seaxnd antderdmoisneatileovnel
Description of any Tabulation of mean
toxic effects/dermal {rritation body weights by sex and dose level
LD,
values by sex with [when applicable)
95%
confidence
intervals
Gross pathology findings/gross pathology report (when
applicable)
8 Location of Raw Data. Records, and Final Report Ofraicgiilniatlatedataau,ditoirngcoptiheessttuhderyeodfu,rinwgillitsbepraovgarielsasbleandatbeHfI to raaelcltcaeiponrteiadgnicneianlotfhpeatpheaerrcfhidinavatlae,s roeipfnocrHltWu.IdiancgWchoetrnhdoistnehgeittfoeimnsHalWIlriSesOtpPeo.drtbeilsoowcroemwipllletebed',
cre140
Page 28 of 32 TP2070 Page 8
DPorsoetocporlepaarnadtipornotorceoclordasmendments InB-oTdiyfeweriegchotrsds
ODbosseervaadtmiionnisstration SAntautdoymiccoarlresppaotnhdoelnocgey records Final report' (original signed copy) nTohte bfeolalrocwhiinvgedsuwpiptohrtithneg srteucdorydsdatwai.ll be retained at Hu but will WAnaitmearl anraelcyesiipst/arceccloirmdastion records IRAnneisfmtrarilugmeerrnaottoomrcatleaimnbdprearftariteouenrzeearnadntdemmaphieunrmtaietdnuiartneycerreeccrooecrroddrssds
00141
:
Page 29 of 32
PROTOCOL APPROVAL
TP2070 Page 9
Pl 2. BBZoy
John L. Butenhoff, PhD Sponsor's Representative 3;
Steven H. Glaza Study Director Acute Toxicology Hazleton Wisconsin, Inc.
Representative Quality Assurance Unit Hazleton Wisconsin, Inc.
(TP2070.3)
2g 2R, +795
Date
'
Date' QA-S
ate
000142
Page 30 of 32
PaTgPe207100
Attachment 1 Scoring Scale for Acute Dermal Reactions
Erythem 01-- NSoingeht 2 - Hoderate
3 - Severe
Edema
0 - Hone
1-
23 --
Severe (raised more than 1 mm) MSoldiegrhatte(ba(rrealiysedperacpepprtoixbilmeatetloywe1llmm)defined
by
definiteraising)
Atonta
Desquamatfon 0 - None
1 2
-
Slight (slight Moderate (slow
impairment ofelasticity) return to normal)
3 - Marked (noelasticity)
Cortaceousness 0 - None 1 - Slight (slight scaling) 2 - Moderate (scales and Flakes) 3 - Marked (pronounced flaking with
denuded areas)
0 - None
1 - Slight (decrease in Ppliability)
2 3
-
Moderate (leatherytexture) Marked (tough andbrittle)
El0ssu- riHonnge 1
2
-
Slight (definite Moderate (cracks
cracks in epidermis) in dermis)
3 - Marked (cracks with bleeding)
00143
te
Page 31 of 32
PROTOCOL AMENDMENTSHWI No. SRO 379
rit or 2 ] Effective
oso 1995"
[Portion of Protocol Being Modified: Page 2. Study Location
feasroenplfaocreMotdhiisficsaetcitoino:n Twoitihdetnhteiffoyltlhoewilnogcacthianognew:herethestudywillbeconducted|
Modification: ue
i
--
Ny;
Gorey
T
=
000144
co
Page 32 of 32
n
_--
HHT No. __50800374 PROTOCOL. AMENDMENTS
Aaendnent No. 2 Effective _Aunust 28, 1095
Portion of Protocol Being Modified: _PEagx e 6.p6.erimDee signn: ts]|
8. Dose Adninistration: (3) Dose Administration [Reason for Madification:_Tocorrectlyidentifivthesizeofthe qauzebandageused
to wrap the ares of application
Modification: Replacetheseventhsentenceofthissectionwiththefollowing |
| Chaos of plication dl)beseti slscuebts
|--(aproxinately9.5-cnx21:cn)securedwithpavertape aroundalledges. |
|--overurappedwithSaranWrap,andsecuredwith Flastoplasttapetoprovide |
occlusive
dressing
study Director prot:
x
Nar
Wap sone
(621/01-07-91)
000145
