Document 2RawbnOX1w36m2N5aMQgOrNR7
AR226 -- 0669
PFOA
Genotoxicity - XL
000907
-
CORNING Hazleton
Sa
MUTAGENICITY TESTON ~~ fl sav +.
T-6358
NM
IN AN IN VIVO MOUSE MICRONUCLEUS ASSAY
"
[EINALREPORT
AUTHOR
Hemalath Mut, Ph.D
PERFO[RABMORIATNORGY
ComVii5en2ng0na0H.aLzVelieertgsoirnngaInP2.i2k(1e8C2HV)
LABO PRR OJEA CTIDT ENTO IFIR CATY ION
CHY Study No. 173880455
SUBMITTETDO
S3tMPCaueln.trMi,nBnueiMslodtiang552104.42-61.00020
SC TUODYMPLETIDOATNE
May 141996
CHY Study No: 173880455
Lof2s
000908
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`CORNING Hazleton
QUALITY ASSURANCE STATEMENT
Project Tide: In ivo Mouse Micronucleus Assay
Project No.: 20996
Assay No. 17388
Protocol No.: 455
Edition No.: 17
pUQrnuoiajtleicattnydwAeasrcsecuorcraodnnicdneugcittnoesdtpheaecctgcieoonrnedsroianflgtrhteoeqtushiterueSdmtyeanantndsdaorfrdetvOhipeeewraoaptfpirtnohgperPifraiotncealeGdroueropeodsrtLooaffbttohhreeatQoaurablyoivtPeyrarcAetsfisecureernacnecde
arnedguloatitohnes.stuFdiydnidriencgtsorfroonm
the the
inspectioands following dates:
final
report
review
were
reported
to
management
InspectionDate Test Anticle Dilution/03/05/96 Dosing/03/05/96 Draft Report Review/05/01.02/1996 Final Report Review/05/14/1996
Eindings Reporied 03/05/96 03/05/96 05/02/1996 05/14/1996
Auditor C. Smith C. Smith S. Ballenger S. Ballenger
he7
Quality Assurance Unf
CHV Study No.: 17388-0455
.
Date Released
2
000909
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CORNINGHazleton
STUDY COMPLIANCE ANDCERTIFICATION TRheegcdlkeasftcorrniesbnePdarsttu5dF.yoowsdausaencddonDDdreuuscgteeAmdbdiemn i2cosmsp1li9i7oa8n.ncee(FwcDitAth)ohTelJGeooeyod2o0L1at9hr75s0)o5wniChPoroaasctiocafeFpreeleaotsions TSahimgeenneaddwmpednaattsca lhTahtvrhaebowwnaoreeuvheoTnostesdghbeyttIegdieyvoofDnihecoosrmdswsohetcheremroeirpmreamdhieenvoefettoet otsf. bsn dn e3b rec seAnd eore heres an apron Solon wits te coven of
TA0leecsordohaysndobcfeohtmeeoifeerweeudpobinhghisSeeapy DrreeesmvuplpoAroFldbeyadyntsex:pBeoricmubemeneteamltiddiot.anrreocosorddanpsims! thfeaceSipelasnonef,CaoAmneinrnghRhe ionsooneraawep.Ferioinor.itheoeftSCpooomnnesionyrgemsHayoEietotnaonhvSeoatbeisfoorfnemeihpoonmoetnso of to ome or em rg a Sod Spe Sobminad By
StudyDirector
M[TeoEmaams iri ch ,PDbor DeparomfeGennte andCellar Toxicology
SSted BCloemepletion
CHV StudyNo. 17388.0-55
3
000910
*
`CORNINGHazleton
TABLE OF CONTENTS
SUMMARY
10 SPONSOR
poe
20 MATE(RTesItAnAiclLe) 21 Clients Identification 22 DateReceived 23 PhysicalDescription 24 GeneticsAssayNo.
Page No.
6
"
7
.
7
30 TYPEOF ASSAY
aon
-
40 PROTOCOLNO.
"
50 STUDYDATES ..................co.... 5.1 InitiationDate 52 ExperimSetanrttDatle 53 Experimental Termination Date
.
?
~
7
orvrasase
7
60 SUPERVISORY PERSONNEL ........
.
6.1 StudyDirector
7
62 Laboratory Supervisor
70 OBJECTIV.E.
.
80 MATERIAL.S
wes
90 SOLUBANIDSLTAIBILTITYY:
100 DOSE SELECTION STUDY .......... 10.1 DoseSelection 102 Dosing Information 103 ReasnduIntelrprtetatsion 104 Conclusion
rsiin sessseen
ran
serrsrsrmsasssarsesd
SE
8
ren
8
.
.
9
11.0 MICRONUCLEUS STUDY
cs
cn
Fe.)
CHV Study No.: 17388-0455
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000911
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CORNINGHazleton
11.1 112
MDiocsreonSuelcelcetuisonAssayDosing Information
120 BONE MARROW HARVEST. SLIDE PREPARATION AND ANALYSIS
4}
130
EVALUATION 13.1 General
CRITERIA
.......
.
-
2
132 Data Presentation and Interpretation
140 RESULTS AND INTERPRETATION ..
150 CONCLUSION
224222000e
160 REFERENCES :
v"
17.0 DEVIATION FROM THE SIGNED PROTOCOL
18.0 EXPERIMENT DATA TABLES . oe
satvere
--
r
oo [STPRRTIT
3 BR 1 cts NT
CHV Study No.: 17388-0455
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CORNING Hazleton
SUMMARY
Mutagenicity Test on T-6358 in an In Vivo Mouse Micronucleus Assay
mTihceroonbujcelcetiivienobfotnheismianrvriovwo apsoslayychwraosmattoiecvaelruyattherotchyeteabsioliftCyorfl:tChDe-1te*s(tIaCnRic)leB.RT-m6i3c5e8.. 10 induce
gInavtahgeedoatse20s0e.le$c0t0i.on60st0u.dy8.00t.heantedst1a0n0i0clmeg/wkags.
solubilized in Six animals
deionized water (three males and
and dosed. by oral threefemales)were
assigned to each dose group. andor mortality
Animals were observed for three days afer dosing for toxic signs.
8B0a0semdg/okng.theInretshuletsmiocfrtohneucdloesuessaeslseacyt.iotnhesttuedsyt.antthieclmeawxaismsuomlubtiolliezreadteidnddoesieonwiazsedeswtaitmearteadndas
dosed by oral gavage at were randomly assigned
200. 400. and 800 mg/kg. 0 each dose/harvest time
Ten animals (five males and group. Vehicle and positive
five females) control groups,
euthanatized approximately 24 dosed with the test antic were
ehuotuhrasnaafttiezreddoasipnpgr,oxwiemraeteilnycl2u4d,e4d8inanthde7a2sshayo.ursThafetearndiomsailnsg
for
extractionof the bone marrow.
pTohleytcehstrommataeirciaelr.yTth-r6o3c5y8t.esdiudndneort
tihneduccoendaistiigonnisfiocfanthtisinacsrseaayseanind
micronuclei in bone marrow isconsidered negative in the
mouse bone marmow micronucleus tes.
CHV Study No.: 17388-0455
6 000913
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CORNING Hazleton
Mutagenicity Test on T-6358 in an in vivo Mouse Micronucleus Assay 10 SPONSOR: 3M
20 MATERIAL (Test Anicle)
21 Clients Identification: T-6358
22 Date Received: January 16, 1996
23 Physical Description: White powder
24 Genetics Assay No.: 17388
30 TYPE OF ASSAY: In Vivo Mouse Micronucleus Assay 40 PROTOCOL NO.: 455. Edition 17
50 STUDY DATES
51 Initiation Date: January 18, 1996
52 Experimental Stan Date: February 20, 1996 53 Experimental Termination Date: April 16, 1996 60 SUPERVISORY PERSONNEL
6.1 Study Director: Hemalatha Muri, Ph.D.
62 Laboratory Supervisor: Monica Vegama, B.S. 70 OBJECTIVE
Timinhcdeeu.coebjTmehicictsriovsnetouucfdlytewhiiasisnicnboovnnidveuocmatasersdrayouswwianpsgolm0yocdehivfraiolcumaaattiiecotnehsreyoatfbhirtlohiectyypotrefostochefeduCrtreeslstCaDrt-ic1l(e,ICT-R6)35B8R. to
Heddle eral. (1983).
suggested by
CHV Study No.: 17388-0455
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000914
80 MATERIALS
`CORNING Hazleton
ARdivuelrt Lmaabloeraatnodrifese.maPloertmaigcee,MIs.traiTnhiCsrhle:alCtDh-y.1IrCanRd)oBmR.brewderseirapiunrcwhaassesdelfecrtoemd Cthoarles mTahxeipmrioztoecgoelnefotricthhiestsetruodgeynweiatsyaapnpdroavtetdhebysatmhee CtiHmVe-asAsCurUeCacpcreisosr ttoo athceoimnimtioantiosnouorfce. dosing.
rAannidmoamlizsawtieorne. hoTuhseedteumppetroasteuvreenapnedrrcealagteivdeurhiunmgidqiutaryawnteirnee.maainndtahionuesdedatu7p2t4o6fiFveanatd
s3e5l2ec1t3i%o.n rsetsupdeyc.twivheelny.tehxecreepltatoivneFheubmriudairtyy 1w7a.s18r.ec1o9.rd2e4d aansd3925..1%1,99367..3f%or. t3h4e.d5%o.se
cs3te2ul.dy5e.%w.wa3hs4e.mn4a%it.nhteaairnnedlead2t.0i.ve8A%h.ucmorimedmsieptercyctiiwavaelsldyir.eeatcno(drPduoerndinaMasar3C5ce.hr5t%2i..fi1eA9d96L1.a2b-foohrroauttrhoerlyimgiPhcetrl/ol|en2tu-schlo*eu#rusdark
abyndthweatmearnuwfearcetuarevrafoir calodnaceibnbtlriauetiofnosrotfhespdeucriaftiieodnohefatvhye
study. metals.
The feed aflatoxin.
was
5002) analyzed
chlorinated
hhraeyltdorrgooescnpaser.cbtioSvnaesn.biaotsirizgseadnfoocrpahsgopiesncpgihfawitaeesds.muisacenrddofosorprgehaconifuiisseimdnsg.nupttehrseiteiancntiisdm.easlT,s.haelkPwaealritnseiortnywn.aehlsehaaavnnaydllmyiezntegadlso,naand
`gaanrimmeanltssoranwdorekqiunipgmweintth,in the animal facilities were required to wear suitable protective.
aArnaninimdmaoalmlslsywweaersreseidgqonuseaedrdatnbotaissnteeudddyufgpororonsueptvhseeannidndadiywvsiedrbueeaflionrbdeoibdveiyiduwnaegliplgylhaswc.eeidgAohnneidsmtapurldiyso.rwteoArdneoismuinanilgqsu, weArlel identified byear tag. Dose or treatment groups were identified by cage card/labelely. bbtyytCpheOen,etterfraomtliilnooanwteoidfontbhoyeftptehhnoertasrxta.utdiyAonnaolylftsexuhtrervaitvahionnriagmx.aalnsimnaoltsuwseerdefeourtthhaenasttiuzdeywdbeyrCeOeu,thfaonlaltiozweedd
90 SOLUBILITY AND STABILITY:
wTahse etevsatlaurattieclde,inTd-e6i3o5n8i,zwedaswasteurp.pliAedclaesara.wchoiltoerlpeoswsdseorl.utiTohnewsaosluobbitliatiynoefdtahtea test article ccoonndcietnitornastoiofntohfisaabsosuaty4i4st5.h2emrge/smplo.nsibTihleitsyotafbtilhietyospfotnhseort.est material under the dosing
CHV Study No.: 17388-0455
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`CORNING Hazleton
100 DOSE SELECTION STUDY
10.1 Dose Selection
Dose levelsof gavage for the
200. 400. 600. dose selection
800. and study.
1.000
mg/kg
were
administered
by
oral
102 Dosing Information
The The
animals used in the weight rangeofthe
dose selection assay were dosed on February animals used in the dose range finding assay
20. was
1996. 27.7
-
s3o4l.u6tiaonnds 2w1e.r6e-p2r5e.p7argerdamjsus.tpfroirotrhteomadloessinagnadnfdemwaelrees.prreesppaercetdivbelyy.makDionsginag
100 11.5
mg/ml ml of
stock for deionized
the high dose water (Lot#
(1000 mg/kg). 19, prepared at
This was prepared by adding CHV) 01.20 g of T-6358.
trheesu2l0t0in.g4i0n0.a 6c0l0ea.racnodlo8rl0e0smsgs/oklugtidoons.eDlielvuetlsi.onsof this stock were prepared for
wDoeseiknsgawndasonaechdiaeyveodldusaitntghea t1i0memol/fkdgosdionsgi.ngAvnolouumteli.neoAlfltahneimdaolssinwgersecheeigmhet is found in the following table.
A totalof30 animals was used in this assay.
DOSE GROUPS
TREATMENT
MF
T-6358 200 mg/kg 400 mg/kg. 600 mg/kg. 800 mg/kg 1000 mg/kg
303 303 303 303 33
All doses given were on an acute (one-time only) basis.
103 Results and Interpretation
All animals study (three
were examined days) for toxic
eafffteecrtdsoasnidn/goranmodrtdaaliiltyietsh.roAulglhoauntimtahlesduarpapteiaorneodfthe
normal immediately after dosing.
CHV Study No.: 17388-0455
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000916
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`CORNING Hazleton
lAepvperlosxaipmpaetaerleyd
one hour normal.
after dosing. all All females and
oanniemmaallseatatthtehe206000anmdg/4k0g0
mg/kg dose dose level
raepmpaeianriendghmyapolaecstaipvpeewairtehdtnhoermmaall.e
also The
showing malesat
lthaecr8i0m0atmiogn/kign bdootsheelveevse.l
The
a1p0p0e0armegd/kngormdaols.e
The level
faepmpaelaersedathytphoea8ct0i0vem.g/kg
dose
level
and
allanimalsat
the
8Ap0p0rmogx/ikmgatdeolsye2l1evheolusraspapfetaerreddosnionrgm.ala.ll
animals at the 200. At the 1000 mg/kg
400, dose
600and level, one
male.
a(p#p6e4a8r5e)dahnydpooancetifvee.mawliet(h4o6n5e04m)alweer(e#
found 6486)
daelasdo.shTohweinrgemeayiensinghgimeadlessh.ut
with
chromodacryorthea. postures,
The
remaining
females
appeared
hypoactive
with
hunched
TlAehpveperlmowoxraitsmaalfitoteuylnydda4td5aeafhdo.orurtAshlilasfraesersmaadyoisnaiirnnegg.suaonmnimemaarmliaszlaeetad(liln6d4toh8se6e)folaeltvletolhwseina1gp0p0tea0balrmee:gd/knogrmdaosle,: Summaryof Mortalities Within 3 Days in Mice Dosed Acutely with T-6358
200 mg/kg 400 mg/kg
[3 [2
or3 o3
600 mg/kg 800 mg/kg
03 on
o3 3
1000 mg/kg
EH
3
104 Conclusion
8B0a0semdg/okngt.hese results, the maximum tolerated dose was estimated to be
11.0 MICRONUCLEUS STUDY
ILI Dose Selection
Based on results 800 mg/kg were
from the selected
fdoorsteessteilnegctiinotnhisstusdtyud.y.dose
levels
of
200,
400,and
11.2 Micronucleus Assay Dosing Information
CTyhcelaonpihmoaslpshuasmeiddein(tChAe Smi#cr6o0n5u5c-l1e9u-s2;asSsiagymaw,erLeotdo#se4d4Ho0n48M6a)r,chthe,po1s9i9t6i.ve.
CHV Study No.: 17388-0455
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000917
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dc2eonnidtornwoialz.sedwadawmsaisneoirlsut(beLiroletidz#eb1dy9i,onrpasrleergpiaaevreaddgeeiaoanCiH8zVe0)d0.wMawtOaersG(aLdomTtio#net1ve9.reeprdhepcaosrmuemdnutmste]nCtHlsV)ith iifhneeemamtleiessct.raorrneiscuplleecetuaitsvaealsyvs.oalyuTwmhaeesodf2o8s1.i10n0g- ms3oi5l.lu2kt,4ionndTsh2feo3r0wte.hieg39hs.te1taranagwemesroeffoptherhaeemdmaeni.ss od aCmdoadlkioinnrggest3h8eso0vl.eu0htiimcolniemw0ais2sa.ob1ac2ik0n0efdgo.otfhTDi-hl6ui3tg5iho8dnsouspoef1(0h03s0vsomolycukmeew)oeFre2T6hp.ir3semwphu.aed3prfeopmarreed bs Gtreretomauaipin)ilwn.gasdTaohlesssleaevsaeslnisi.gmnaeAldssweectrohendsongulrdyoyuupasoenfdawinnaistmhadelosssea(ddyewsi8it5ghnrahetepeldhaSicgeehmcedonenuesdfsoorfoasne which died i the primry dose group. ShTpaeprnvreoasxntiimmiiamtleeslg(yfrio2vu4epm.haoluVeresshaiscnildre aidnovsdefipneogm,satlwieevsre)ecwonemcrrueodlreagdrnodiuonpmhel,eycsausomsnieyganmedunr0edacnaicmhadloser. diisoesfreodudnowdsiitinhngtthfheoerfeeotxlrloaawcriitcnilgoentoawbfelretehecubhonaenamiaznedo,proAxnimualtielnyo2f4.he48dwedm13spoouarsr
Dosing Scheme for Micronucleus Assay NumberofAnimals Assigned
Tresmens
PMPYriE; DMoEsTe GrRr ouT SSeeceonn dremaDiosee.
T -- es -- 200 m-- g/kg --------5-- 5 -- 55 -- 55 --M-- a- c F-- em-ale
400 meg
ssoss oss LL
$00 meg Vehicle Control, deionized water, 100mikg
ss oss oss ss 5 5... LL.
LoPs+otsiiviverTeehCpeClooaanncntetiromaolanl.liCmsCayalcysslscoiWpglhhnioeocdsphpthdhoiatoemhdseidnpseeh.hc00oean00dmparmimriymgdgadrehoys,gedog5rso5ug5prsouw-pea-r-td-hoeshedg. han.dwL eteoocnhlyL wAeRedC1,0
animals no ed 3 replacements bere hansbed at i Sent es AL
aTnhiemaalgse woaftshuesaendiimalhssaatsshy.imeof dosingwas ight weeankdonse day. A tol of 120
Volumes dosed were 100mikgand wre based pon individual animal weights
CHV Study No: 17388.0-455
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CORNING Hazleton
120 BONE MARROW HARVEST. SLIDE PREPARATION AND ANALYSIS rpAeetnmeotthvreeadat.pipornToohpfretimahteaertmhhaoorrwavxew.satsTihmfeleu.asdhthehderafinrniogmmasotlfhstewibesorsneueeeaauntndhdatnerapaiinipszhfeyedrsrewesidotofhbCcoOetn,htrfifofelumlgooerwateudbweebsyr.e wpceeolrnleeatisntpihrenegatdis3sou-ne.5smitihdeebssouavpniednmaeaistdearrniutemdw.a(osnTreheetmuosblveiedfdeosrbweyaeacrshepiafrniaietmidao)ni.namneFdtophloalrnotowilio.nngsancodeftnShttieafiupngeeadetirinon to cMoavse-rsGlriupnpwedaludsisnogluDteiopnexf*olmloouwnetdibnygGmieedmisuma,(Schmid. 1975). The air-dried slides were
ueTsnhetedhrs1lo0iedryeetsceowr(edPrCethEce)osedtoeddantoaf.rormOaonncaehlyrstoihmsoa.uisacanndedrsyPctoChrrEeosdcypfteoerr(maiNnciCrmEoa)nluccwelelelrieraatsincodo.rtedhS.etapnTodlhayescdhfrrfoeomqraumtesniccwyeroef CPmeiClcEr:soCnDpu-re1els*ee(anIttCeRidn)ctBeheRssswctoaarsiendeixopprtaeibscosufetidel0da..s0-pTe0hr.ec4e%nnotrmmiaclrofnruecqlueeantceydocfelmliscbraosneudcloen itnhethtiostal
NThCeESfroebqsueernvceydoifnPtChEeSopvterisfuiselNdCs EwhSilweasscdoertienrgmtihneedfirbsyt s1c0o0r0inegrytthheroncuymtbeser of PCEs and 130 EVALUATION CRITERIA.
131 General
iMTnihcgersochrnaiuptceelrdieaimfiwocerrrotehneudcailrdekeilnyiofcsictcaaasitinioeodnnaalonlfdymogieccncreuorrnaeuldcl.lyeirMowiuecnrdre,ontauhlcotslheoeouhgfhaSdaclshhmmaoirndpdb(a1o9nr7dd6e)r.s maansdowtehterhaemnigcoernnoeenruamclillcyeraobtneeudtcwlceeeulnsl wn11oa2ts0tcahoneudmnit1cerdotanhsuecalsneieuzesom:ifcttrhhouensutPchlCeeEao.ctceTadshPieoCnuEan,litncooefltslctwwoirtih(nogr fmorPeC)EmSicarnodnuNclCeEi.s (Tbhleuissha-ignrienygapnrdocreedd,urreesppeecrtmiivtetleyd).the differentiation by color 132 Daa Presentation and Interpretation DpaIentdraifvoairrdemueadsluaumnsmiianmgrailazndeaadtnabalayyessieasxlosaofndpvraderosiesanentcgeedr(.oWuipTnsheerf,oarn1at9lh7ey1sd)iisfofonefreetinhttehseterimdueanttpsroiawnnatsss.formed oh(fewthveearrnoiavgnaecrneioawunascs)esspiargroncpiofhritociamonnotsog(fepncee<lols0uawsan.i)dtD0hurnma5ninekct)rtto'.rnsaunvcselfseotrpme(erDdua(nnwnihemearn., v1aI9rf5it5ah:nec1ea9sn6aa4lr)yeswisas used to determine which dose groups,ifany, were significantly different from the
CHV Study No. 173880455
2
000919
`CORNING Hazleton
negative control. sex combination.
ATnhaelycrsietserwiaefroerdperfeormted seeapaprorastietlim yveforiresepaocnhnsheaiirnvvesontlvteigdmae and.
dsetatteicsttiiocanollfy asriegpnirfoidcuanctibdlosee-arnedlastteatdisitniccraelalysesiignnimfiiccraonntupcolseiattievde
PCES, or response
the for
at
least dose
one dose level. responsenor a
stAatitsetsitcaalrltyicsleigtnhiafticianndtuacnedd
neithear statistically reproducible increase
significant at one dose.
level was scientific
considered judgment
negative.
In either case. the final decision was based on
140 RESULTS AND INTERPRETATION:
dAulrlaatnioinmoalfstwheeraessoabysefrorvetdoxiimcmseydimaptteolmysaaftnedr/odrosmionrtgaalintdieps.eriAoldlicaanlilymatlhsroi ugthhoeutvethhiecle
and positive control groups `appropriate harvest times.
appeared
normal
afer
dosing
and
remained
healthy
unil
the
aAfltlertedsotsianrgti.cle dosed groupsappeared normal immediately and approximately 1.5 hours
hAoonpueprrfohexamiramvleaestte(lg6yr7o62u42p)hworeuorrems aftofhutenr2dd4doeshaiodnu.gr.hAaaltrlvtheresetm8ag0ir0noimungpg/aaknngdidmooansleesmalatevlaeeill,(doon6see75ml3ae)vleeflrs(o#amp6pt7eh4ae8r4)e8dand normal.
Afforpuopnmrdotxdhiemadsa.etceolOnynde2a3rf.ye5gmhraooluuerp(sa#afn6tde79od0no)esfifrneogmm,altaehte(tshee6c78o60n60d)amrfgyr/odkmogstedhoegsr7e2oulhepvoeaulps,poheanarerveefdsethmyagplroeoauc(tp w6e8r0e3)
ive.
(#Ar#p0p5urp6o)7x6iw1me.art4efe8lohyuon4ud6rdhheaoarudvr.essatAflgtlerrorudepom;saii6nn7gi8,n4ag.t 7atn2hiehm8oa0ulr0s amhagra/vlkegsdtodsgoresoelueplvseevle6sl7,a3p0thp,reseaeercfoenmdaalreysdose.
ed normal,
Approximately normal.
70
hours
after
dosing,
all
remaining
animals
at
all
dose
levels
appeared
rpToahletyctaehnsrtyooamrfattticihlcee,ehrTay-rt6vh3er5so8tc,yttiiemnsedsuo,cveeedxrcnteohpetslifegovnreiltfshiecoabfnsetemiranvlceerdseaifsnretoshmientvhmeeihci4cr8loehnouccuolrnetharatorlevsdesitnoeither sex
800 ery
mg/kg dose close to the
ghriosutpo.ricTalhcionitsraolsdaiasttai(camlaxaniommuamlyo.f
for
the
mean
ofthis
fthe group, 0.30%
0.24%) and within the published
is
chsoiinsgttnroiorfilicsca,alndwtiaittnhacmr(eeSaaasnlessaamionnndmeicsatrnaodnnduMacarlvdeoaeturernodirnsP,CoE1fS9934i)n..0bo6=Tt%hhe0s.ep5xo0essi%taaisnvedccoomnptarorle.dCtPo,thdeuvceheidcle.
4.24=% 0.47%for the
CHV Study No.: 17388-0455
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`CORNING Hazleton
males Table
a| nadndfeimnadlievsi.duraelspaecntiimvaelly.datTahaeredaftoaunsduminmaTraiblzeesd
2bythdroosueghgr7.oupHiasrteorpirceaslecnotnetdroiln
data are presented in Table 8.
150 CONCLUSION:
mTahrertoewstpmoaltyecrhiarlo.maTt-i6c35e8r.ytdhirdocnyotteisnudnudceerastihgenciofnidciatnitonisnocrfeatsheisinasmsiacyroannudclies icoinnsbidoenreed negative in the mouse micronucleus assay. 160 REFERENCES:
Dunnett. acontrol.
C.W.:. J. Am.
AStmautilstt.iplAesscoocm.p5a0r:i1so0n9s6-p1r1o2c1e.dur1e95f5o.r
comparing
several
treatments
with
Dunnett. CW. 491.1964.
New tables for multiple comparisons with a control.
Biometrics. 20.482-
aHnedddSallea.moJ.A.n, eH.itM.eF..:M..ThKierkihnadrutc,tiBo..noLfamrsiecnr,onKu.c,lMeaicaGsreagmoera,sJu.rTe,ofNegweenlolt,oxGic.iWt.y. Mutation Res.. 123:61-118, 1983.
Sreavliaemwoonfet.hMeFm.ouasnedsMtaovcoksurunsiend.aKnHd.the(i1r99p4u)b,liBsohnede mmeaarnroswpomnitcarnoenouucslemuiscraossnauyc:leaus frequencies. Env. and Mol. Mutagen.. 23. 239.273.
Schmid. W.: The micronucleus test. Mutation Res. 31:9-15, 1975.
SMucthamgiedn.sW:.:PriTnchieplmeiscraonnducMleetuhsotdesst
for cytogenetic analysis. for Their Detection, Vol.
Chemical 4 (A. Hollaender.
ed). Plenum, pp. 31-53, 1976.
Winer, BJ: Statistical York, Second Edition,
Principles 1971
in
Experimental
Design,
McGraw-Hill,
New.
CHV Study No.; 17388-0455
1 000321
:
`CORNING Hazleton
17.0 DEVIATIONS FROM THE SIGNED PROTOCOL.
I.
sDeuleecttoiounnsktnudoyw.nthreearseolnast.ivoenhuFmeibdriutayrywa17s. r1e8.co19r.d2ea4dsa3n0d.12%5..
1996. for the dose 37.3%. 34.5%,
s3t2u.d5y%..th3e4.re4l%a.taivnedhu2m0i.d8i%t.yrwesapsecrtievceloyr: doaensdM3a5r.c5%h.2.
1996, for the micronucleus This had no impact on the
animals or the integrityofthe study.
2 D19u9e6.oaAlttehcohungichaltheerrsoyrs.ttehme wwaatsenrotsycshteecmkewda.swnotacwhaet cskaevde aiolnarbFleebraunadryhe2n4ceantdher2e5..
vas no adverse the study.
effetcs
on
theanimals.and
there
was
no
impact
on
the
integrity
of
CHV Study No.: 17388-0455
Is 000922
-
CORNING Hazleton
180 EXPERIMENT DATA TABLES
CHV Study No.: 17388-0-455.
16 000923
: `CORNINGHazleton
Tans ronson CRONOACTHSLUMMEARLYThSBkE
Ww
WT en
TE on mscoinenn Come nxe oamiasn an ci
RANNS t Hn son osm| osnon oweon
ocnaioin oni
oomiein|| comoernonseunsee omer| sarin omer
eveiln tonaionn|| coerritesn oonmceonm
Be smon onise owen| ore owen "tsran mncmran come
CHV Su: mssoss
"
000924
Toes
`CORNINGHazleton
ronsoSn ICHTOETNDUIUCRLNEALLOSATA
stars ros
-- G sro. om SRh R me ATSE
e Pe eee e------- w r m
BoD
mena owes B # pe oy8 oe
--
wowB)ooee
LE
modo woo
oBomu oL3 o#036 _m S CHB irmmmT o, E Em
CHV Study No.: 17388-0455
8
000325
:
Tans
`CORNINGHazleton
pa--HCRONUCLEUS TET INDIVIDUALANAL OATS
resasics mass
sssavso. um
-- eGAR J RTS oee e m oe cm EBBoo oon
reruns
or worowH
owBBBooobiomOOHH
mo BBooib eO8wH
m _-- W wwwo oo #
T E E Rm E RR E ,
CHY Sug No: 738.0455
.
000926
:
CORNINGHazleton
TABLES
MICRONUCLEUS TEST- INDIVIDUAL ANIMAL DATA
SPONSOR: 3M
TEST ARTICLE: T-6358
p ASSTARYEANOT.ME1N73T88 e ANIMAL pees RATIO
_--
TNTUMBERi|eSoCnErce FcEENNCCEE
_H--OUR HARVEST
MAE
TEST ARTICLE
20 mang ooemy2 o03 s
oona 3 ooxs
00 mpg 00 meng
oe
I
o oauoao oowisw
ao on
--_-- MPCNE==MPioclryocnhurcoimeasdsicerytvocyte M`NCNE =PNCoErSm=ocMhircormoantucclreyaehdocPyCtEeS
CHV Study No.: 17388-0455
2 000927
:
`CORNINGHazleton
TABLES
MICRONUCLEUS TES-T INDIVIDUAL ANIMAL DATA SPONSOR 3M
TEST ARTICLE: T-6358
a ASSAY NO: 17388.
--_-- TREATMENT
TAMNNAUIPMMBAELRoppo0eesr5PpERCaENTNiCCOEE
--_H--OUR HARVEST
FeuaLE
TST ARTICLE
00 mpg
oa
08
oe
03
woo on
00 mae om 0 ou
on
os
we
oi
100 mae oonn
001s
_--
ws
on
M* ANni=mVailcfroounnudleeusss
PCMEN=PPCaEl:ychrMoimcartoenuncetsiehd ePCEs
NCE =Normochromti ence
CHV Study No.: 17388-0455
21 000928
-
CORNING Hazleton
TABLE 6 MICRONUCLEUS TEST - INDIVIDUAL ANIMAL DATA SPONSOR 3M
TEST ARTICLE. T-6358 T ASSAe Y NO. 17388
--_T--REATMENT
ET --
TESTARTICLE
200 mang
TANOUIMvMBOAeERLso0pPEESpSPPERCaNETNCiCOEE
os ost
on
on
"00 mang oon no oosse
os
on
00min
om 0 om
od 08
--m oe ok
MPNCNE==PMPCiocElrSyocm=hurcMoiimecawrsdacneucrioecneydtPeCE
NCE = Nomochromaic eryrocste
CHV Study No.: 17388.0-455
2 000929
-
`CORNINGHazleton
TABLET
MICRONUCLEUS TEST- INDIVIDUAL ANIMAL DATA SPONSOR. 331
TEST ARTICLE: T6358
A--S_SAY NO: 17388 --_--TREATMENT "_orm maRvesT rest ancts
ous omens
omen
NNAOUNMOBARELR |CgreEpcgyS,PnEwcaNnnCioeE ooow 0 oe EGCn oom+ ma ae0 nw
0 murs ona _" -- Ca aE o 0 on SI3CAEN=PMFiCcEoromrMceerosonsedensedeEs NCE- Nomechvomae cvrocrc
CHV Study No.: 17388-0455
23
000330
:
CORNING Hazleton
TABLES MOUSE MICRONUCLEUS HISTORICAL CONTROL DATA 795 THROUGH 1295
CMERAONNOFE1E00N0EPDERFAENEIMFAELRSTERE TNTeOaRnEeSsrCE aes roves torn | wae vias
AVG 00e000
nasa mts aWxo
NCrE = Pomcomvenaaetmoavrere
sensteene
non0oos oomsoms| 0s0eomn nensun
diome%ons seonme| osmoneon se0%en
CHVStudyNo.: 17388-0455
2
000931
PoRwOTOsCtOoLrwmo.. 433. EDITION 17
CORNINGHazleton
IN YI Movs MICRONTCLEDS Assay fSLgsooaasrbsnocuiraonancgtckoerHyIainznlPperaratcococgtnorirecIdsenascn.(caGenL(dPCw)HiVthc)Rehe'gWuSitloliPalnstailcoaontcnsed.puocrtsThtwihisilslprsobtetuodcysoulbi.jnecccteoimvptioloissau:ndciesc.hwasibeytrheG.uGaoiooitdcy conducted by CHV ax 5200 Leesburg PikeC.orViineinnnga,HaVzilregtionniaInc3.310T7he seody iit be
PART 1. SPONSOR INFORMATION AND APPROVALS I. SPONSORIDENTIFICATION
Company Nase: _3M Address -- Stlaandt AMNy
I. fZsESrT muaARTICLE rwIepEmNTpIrFIaGAnToIOnN:: T0 T-=6335588 --_--
TIL. IESTARTICLEANALYSIS oCDfperteetharecntieSnpraoicnsiseooinrc,sofasthdeeftiensetdaritnictlhee GsLePabirleigcuylatainodnstheis ttehset afcecsipcelnesibility
IV. MOTIoPFRIEGUCLAATORTYsmImMOssiNoN
JTIIhUap,EbBSmu,oilrsadDateeiosornnyot.roirefcvCioiHemeVdlw.ym1a6iwna`iPtltlalheianostsreheepiaGnmLcdaPtisctaortefeer'gsuwlshacsithtieuoddnuysl,eisocfoinnstsuetunlddtieiednsgfwolhraibceoherpastbaoiireliseesonyder
the cesults of this scadys
ch agency, Lf any. Bight racers
= Undetermined = -- wr C--O
m~--d wow
PA-- Z mats 0 --_ --
o--D gparive
orep 3 orm
wos
of 10
000932
FROTOGOL Ko. 45s, Borrow 17 v. moor pares
Proposed Experimental Stare Dace: Fropased Experimental Termination Dace: Vi. aPPROWAL oF STUDY ERoToco scady Director:
FemaTethe Wer TR Sponsors Authorized Represencacive: XSlauttl ooww
CORNINGHazleton
Dace veces: BL /r
wos
2 ot 10
000933
PROTOCOL NO. 455, EDITION 17
CORNINGHazleton
I omer
PART 2 - STUDY PROTOCOL IN VIVO MOUSE KICRONDCLEDS Assay
ePTolhleaysctohobrgjoeenncaittciivceactoeifrvyittthhyrisoacnysdtteuddyisstreiusmptctieoollnesvaoflinusttmheoeumsaeitteebrsoitnceamarpitpciarcrolavetuisf.norsiinve
1. prparIoNs Mc1aihgcrsormoonbsueochmlieen(udss):atamnaidt/soomtrailclofacanhacrpeohnmataseteii.cn cbAhofrdyto,emroscocomenelsoipsfhtraiasngege,enotft(hsesysa,etiwrehich cncyuhtcrolopemlioa,ssoman.ned(s)cayandforfmragsaienngtl(es)ormmauyltnioptlebemiicnrcolnuudceidelininthethedaughter
TI mations
dT2iheveincsmsiiocnraondn(uscctlheaesituds.artte1is97tc5l;ecsanHwadhseielcrehveoicanstaeralf.erraep1i9d8w3i)ts.hcreneoMnriacarfloonrositctileeasssiteosrgeeeneilc
a(fnSoaerhpmmheiadcs,efcao1n9md73c)ch.ernomobIsenomtsehcsiosreodarssCdauhyrr,ionmgopsoolimynectherfrorpmahagatasieecntbseercylaeeshtsrseocbtyheeehnyisndp(eshruesrsiiesng
gDiDxenuctrreitucnhdgteeidomb.naotnwueohfriacmltaieiccoirmnooiuncfuaorcronlenuecieslrceyiolcnr,herdnooibnffl-oanprsurtcetslheeetnaoctp,esrdrefyscteeehnmlecilsenscyotfienMitthhceeermcmyaceclolepeltn.assei.s
|
afifnafceitclrtieitanatgteedds,Cpeilanlnddlep-otfpiiumbleeartiinofvnuosnlcvteiidsoneilniomrsienafarotcrehdm.ia"ntgionTfeosarstmiweasettlaetlpihuhesara.ssees spreads
c(lcahsacoig.eni1c975a)gents can be detected through micronucleus induction
vam
A mioals Y10o2u0nwmgeeCkhasadrulloetlsdmaRalcievetrhaendLatbifoseremaatlooefrimdeoissc,iengol.facwt.ihlelorIbReHarspieeeecnacihna,ted8. Sprague-Dauley. Inc. This scrain has been selecced to
ares
3 of 10
0003934
I
PROTOCOL NO. 455, EDITION 17
`CORNINGHazleton
maxinize genetic heterogeneity and at the same time
B. ControlArcicles C1an0ydcmlwloi/plkhglo)spbewhialmaliddmeibnei(suCtPs,eerde8da0smbygt/hkoegr:aplosdgioatsviiavngege.cvoonltTurhmoeelvoeafhritcilcele ucchsoeendcrsoaflmoeratrrhoteuitcelteesastw.ialalrntdiccolcneosnicasuntrdrowefinlttllhye bwesiotalhdv,menittnhiesotretrevseetdhicbyl.e tyaodclmcuiinnceileswtiealrnleddnionttoatemhxoeucneteesdxp2ee0cqiummalel/nkttgaolftoahrneimomaralaxsli.mguamvTavhgeoeludmaoenssdingIp Aadsnsianyisatrreatviaotnesr., 0T.h5e1 avqeuhiecoluess cgaernbeorxaylmleythyulscedelliunlotshse solution, or corn oil.
Vv. EXPERDONTALDESIGN A. Animal Husbandey
wAsiLelLvlenapbeppleriicsacoballgaeeteddCuHrVbiynSgOsPeqsx.uawrialAnlntiimbnaeel.sfowalinlldolwweidbl.el hAobnuesiemhdaoulssuepd to
uSacpeempteohroauftsiuevrdee.upnrdi7eo2rrF ttohe6exfFpo.elrlhoiuwmmieinndgtitciynl,iitmia5st57tiico#nc.1o5n2d:iAtniiLominagslh.st
wc(ayPteulereri.nwaid1l2lCheorbuetrisafviaelidilgaLhbtal/bedoararadkt.olriybAiCtchuoomm.wmercT3ih0ae0l2)fdeaieedntdistap
Dajypndeazcloiycfzaiezedbdobnhyse,atvhyeormmgeaatnnaoulpfsha,ocstpuahfraletaretsof,xoirn,concchelnotrriantaicoends of
nruettrrioesnptesc.tiveThebasviasterforis sapencailfyizeeddanmdbiicssrnponeoucraiglfalinyeidsomns.a
Apbneeiismntgailcsipdlewasic,leldheboneavyqsutmuaderyta.anltsi.nedallfaolrinaittyl.easatnd 7 hdaalyosgenbse.fore
.
Aancicmoarldsingwiltlo Jrocedures.
CboeniansgsigHnaezdlettoonsSttuadnydagrrdouOpsperaattirnagndom Animals will be veighed prior to dosing.
wT3eh8ie.gyhtwsiT.lrleatbmAeennidtooaslegsdrouwbpiaslslewdibleulpounbneiqtuhieedleynitniidfdiiveeinddcuiafliedanibmyalear
label/cacd.
by cage
ss "of 10
: 000335
v
PROTOCOL NO. 455, EbtTioN 17
CORNINGHazleton
baSeneinariaetlqasuriyroercdawgeocsrokivwneigalrlwisbteuhiitunasebdlt.ehepaPrneoirtmseaoclntnievfleacgihalarinmtdeilneitsnsgwainlld equipment.
5. Dose selection
msToahmexeimhuiimgnhditcdoaoltseieroantgeedonferdaotsloelx.yiciwtiTylnle (hebie.gg.hs.edldoeescaettehds,haosduledp8r0%epsrsooidfuocntehe vO(ifNlClErSa)nc.oircmOaolnfley-BhCaEbslefutsoaenddnoaomsnmeo-tchqheuraorimtncetirecrmofeedrityahttihesrocnayintdgehslodvosdeose alcnehdveelilssi,ketlrhieehsroepofeodcrteitvhearlteyc.aomweeUasnkedecodflaascohgiegnh wdiolsle biencdreetaescetsed,
FIffiannndgoienfgianpdpsirtnougpdyrisacttuaednyabveniglpelerfbfeoirnm3dei0dn0.g0 mdgaT/htkeag.tacoepThadeovsaediolsatebelseLt,eevdeolfsnranrcgheeesteddose "ill be issued as tn amendment.
20SERANGEFTNDINGSTUDY. FTBhreeomuapldseo.smeicEreaa.cnhgefofindtihnegfisvteudygrwoiulpls wbiellcocnodnutcitsetd oufsin3gmafiisveantgreastment
Group Designation and Treacmenc Regimens
Stoup No. MNaulmeber ofFeMmilcee moue Dur(paatvieon
:
1 -_--
s3
r
3
2 _--
3
3
ro
3
_--3
53
0
5
" --_--
5>
0
5
---_5--
33
0
3
wes
5 of 10
000336
PROTOCOL Ho. 455, EDITION 17
`CORNINGHazleton
Tthhaet rtoeustte injection
woaifrltliacdlmbeeinicemshptalrroaayctetideo.rnisvtiTilhclessebeprroeoucrtalelusdegoafvoargaaedl.mignaivIasngtert.ahteiIopenvehntave
abdeneinnissetlreacctieodn bfeocraustehisthteeystareprotcheedumroes.t not exceed 20 ml/kg for oral gavage and
cTohmemondosrionugtesvoloufse IP administrations.
will Other
airtonucetrreaiscsulsocfuwliaaldrlm,igneisnsuetbrr-aacltulityoanneboetuhssatolamudabmyiilniibzseetdruasteiidnonaosnree oroifnbtytrhaevfeenefodo.ulsl,owTihneg test
issonoldluivtveiinodtnus,a:l worabtoedcryo,rwne0io.gi9hl7t.ss.alALiLnDeo,saeni0ml.ae5l%vselasvqiulweliolulsbecbedaorsabesodsxiygmbneaetsehddylbcyueplaolnujose
Protocol amendment.
wpBiroledlpyarbweeedigphartnesdpahwreiellddl jaubtsetatmpabrkiieeonnrtprtiotoerdmopsetironagtd.uorseisnDgo.sunitnigDlossdioonlsugitnifgoonrsm(u0wl-i2altlionbe hsoiunrgsl)e. dosAeL.L animals will be euthanized 3 days after receiving a
The for
tahneizadlusratwiiolnl
be of
inhalation followed
tohbesersvteuddy.daiAlnyimfaolrs twoixlilc bseigensuthaanndizmeodrtablyiCtoy, by penetration of the thorax.
WVTiihLleLldatbiehleynusbeoedbsatesorsviaegstntieiodmnastfeoorf thttehoexiMcasxuibssmyeumqmputeTonomtslercaaynttdoe/gdoernDemotosirectsa(lMIiaDts)is.aeys. Ddaotsaes MICRONUCLEUS STUDY
C. Dosing Schedule and Route of Adminiscracion
AHNadormrvimenasiltsltywriaaltnlioanbc)eutewaiplpdlroosxibienmgautsreeeldgyim(e2sne,e (4Ts8ai,bnlgel7e2bheloouwr)s. after
aapdpnrionxiisccactaetliyon2ofhotuhres taesftterartaidcmlien,isacnrdatiaocn of control articles. A total of 110 animals will
btehe
aautnsiedme.aalcsh Ectqournaelsaitsmnetunimtnbgergsroofuopf3.-1m0aAlmneaslaedasdnditanifdoenmaa3l-l1e0sgrofwuielmplaloefbse
used may
Obfe dtohesedtesats toxicity is
maatseercioanld.aryThdiosseggroruopupwiwlilchbethdeosheidghifdose expected at the high dose and the animals
asinenycotnwhdhisaircyhgrddooiusepewpgirrliloourpontwloiylelubtehbaeunsaedsdeita.earsmirnTeehpdelacbuesyemethnoetfs sthtfeuodry
director. Freshly prepared solutions will be
wes
6 of 10
000337
.
PRotacoL No. 43, EDrTION 37
CORNING Hazleton
eCmopileoyevdi.neTahnedsmnoirmenaitsicwyi:ll be observed daily for
MOSER OF ANIMALS USED FOR MICRONUCLEDS AsshY
Harve(shtalTeimeansdAfTteemmrleTnrseucment
GroupNo. Irestment
31 eremscteieveccaommriel
26 Hours
s3e4s3
48Hours
IoCn
22 Hours
RO
ITotal
sOeHs
5DFaoHnighy tposee sssiitsssooisstusss oSsTlisyioBaniIlinEd
Tora
Zea 1e1s 14s sess
oTtrhhaeel vr`oegunatvteageot.fhat1a0dmcieirnntijseactrtrtiaioccniioewnilvtlihlalrbeacbeeseorpoilrseaytleiesg.eavapg"riean.ce lusIen
otGfhoena'indnoagsitnvioscltuormmaecoviiolnoluhtanevoset oebfxeceaeneddasienl2is0scaieLee/daktgi.boecnaufTsoher.esehuyis.osstteeeesst
Srocadure. oeher coutes of adainiscrecion shut nay be
Sininitrations or by fess
BS. EE ESxhutotx rrhaaacxnt t,aisor inaa.nda oufhlc TiBlnhodetnbeseLi aMirwaaribo rotruhbn oowwnCioeyls,lwifbloelllfolbuueesdhseebdsysvFperteonnFeoctrhaesmibooonnoe.nofandthe SCreainns'te(rotneedtucobecefnocreiefaucgheaCnuibmesa.containing sod at movin
E. PreperoaftSliiodens
OFSfuopleltEoheTwAiTnpAgeDl:lceeVrncAveLiiltlubegabtecieomsnopvreetdaod bpyoenlalesstpliirdtaehsteiostnnidsssusnedi,rpaotrrhiessieo,ns HsTohaueyn-tsGilrniugdmeawslidcvhilSlcoolvutechreisnolnipbsea.ndfiGxieFedomrsianc.onmteanrctoh.alnpooelfs,tmeicssicsaa:dinesdi in liebe noes For amaiyats
wos
ot
0009;
PROTOCOL HO. 455, EDITION 17
CORNINGHazleton
Fo scortheiSlnidges ugAaEmnnPibrmaeeatrlst.seeosfdptTaPhsCewEisplflerarencqbaeuelneytnazcueymddie.corftooTmnhiusecccrlooenronserutmceoaldnleenc-tetelhdlosuscaebnladlssedFwCisElasl tphneeer afzroeuqnudenc0y.0o0f.4m1i.cronuclei in the ICR mobuascekgsreoruedin is PT{GhNEeCSEsf)arnecUqiuleNlnCEc:ybeoobdfseetPreCvrEemsdinveiednrsutbhsye smocapottruiircneg feitrehyeltdhsrmoeucmnybiteteres of scoring the first 1000 erythrocytes on the slide
VI pam
TSohcuehnadic,driat(le1tr9h7io6au).gfhorsWlitachorenodniudcaelnndetsirfiianrcega-tsidhoaanrpkelodyf gecur. Mlcronuclei have sharp
msitcarinoenducalnedi micronciel
agreenertshioisye of sccnsioiily
mC1ie1lc2lr0onw4uinctdhle1ma1ot5reedthecchealsnli,zeonneootfmiTtchhreeonmPuiCcEcbl.roeorundsuTechrlesieeuauscnn:oidtunattorhefuedsgsatecehnoereiornnasegiolcy1e6sbiteonsneseoin
micronucleated PCE. not two (or more) micrometer"
TFchoeeldycshrxreaosimpnaeitcnicgcivpearlnoydc)e.nduorremopcehrrmoimctsicthescydcihfefaecryernets.iat(ibohnaibpyegcuoelyoracohf
Data resentation
eTfPsCheByesstb.hedcrao4ccnaoydftcemtoshipecocfrootrrneaudteciaolwceihslolfteedxpiponePlcrCylEicusnhd,reomttahhceeicpnuetsrobceenrnotraomgfsecBhoCifEosmmaistcclvoeoremds,cletrheeed
ancal anima
Eraluscion criteria
ffTSeehasiebepnceicntfesiiieoctnaenrftoiorsfdaaoftsoerrl-eerpaaersloptadotusecoinditebilvieednocsarreneedasspeosncsaiecnimsiitscirc&oanlslueycaiseisaistgcenisicfaitFcleaybn.t opfestihoeve
nj155el7ie8btc1,hsesrcisicacaolsnltsyaitdisesirtgeindciafnlieclgayanctsiivagenn.difircIelnapenrvteeoild.cduhcoeisrbeAlecrtaeestssetap.cornasetrenhtesiecplafieratnaotlohneedeecdstoesemen
ased upon scientific judgement
iion
ass & of 10
00083
PROTOCOL No. 435, EDITION 17
CORNINGHazleton
VIL 1I8USETRFRETATION
JThaeiaanncaelys(iWisneosf, homogeneous) or
`trh1ai9ns7k1)tdraatonansfweoiirltlmheedrbeu(nwptherecanfnosvrfamoreridmaenucdseisn(gvahseaenn
avnaatliyssnicsesofare
8ghIEofeottuetepshrsteo.gea(innDfaeulonynuaenssyti),:s,paorcf1oe9p5ov5rsa;tiriigoan1nn9i6csf4ei)coafiwnsitclleslylilgsbdneiiffwfuiiesctreahednntmttioc(fredro0eont0muec5rl)ae.isne&pewbrhuiacmnhimmaeslosr.re
gtiodneezoaln.d sAenxalcyosmbeisnawtiiloln.be performed separately foernesancekgahtairveeest
VIII. aEpmRmicEs Dturnenaetrmte,ntsC.Uw.i:th aA mcounlttriopll.e cJo.mpAaar.isoSntsatipsrco.ceAdsusreec.f.orS0coim1peasreirngizsievetreaels. DBuinonmeetttr,icsC,.U.2:0:4N8e2w-4t1a,ble1s964f.or multiple comparisons with a control. #HNeeBwdeedalllse,u.reGJ.Ao.f. `gaMenindcoetS,oixliaMcm.i,otnyeK.,irHk.hMFau.rt:ea,tio3Tn.h.eReiLsna.dc,uscen1t,i2o3nK6.1,o-f1M1ma6ic.Gcreea1gr9oo0rr.,ies3.11s. Schaid. W.: The micronucleus test. Mutation Res., 3.9.15, 1975. CVSohcle.hmaiidc,al(WA.McacHaoglTelhnaese:nmdiecrrP,orniuneccd.il)pe.luessPtlaeensndtumMf.eotrhppoc.dysto3gf1eo5rn3e,tTihce1i9s3a6n.baulsysseissi.onIn, fMienGerra.u-HBi3l.l:, HeSwtaYtoirskt,icaSlecoPnrdincEdiipclieosn,in1E6x7p5erimental Design,
IX. REPORTFomAT
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-- AMENDMENT TO THE STUDY PROTOCOL Page I of| STUDY TITLE: IN I0 MOUSE MICRONUCLEUS ASSAY
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Section
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Date
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