Document 0gVVEm0vpRVYXVKnKEydbrLBJ
CORNING Hazleton
MUTAGENICITY TEST ON T-6342
IN AN IN VIVO MOUSE MICRONUCLEUS ASSAY +
[EINALREPORT
AUTHOR
Hemalatha Murli, Ph.D.
PERFORMINGLABORATORY
Corning Hazleton Inc. (CHV) Vi9en2n0a0,LVeiersgbiunirag P2i2k1e82
BE
:
;
CHV Study No.: 17073-0-455
SUBMITTTEDO
3M Corporation SBt.uiPladuiln,gM2i2n0n-e2sEo-t0a2,5351M44C-e1nt0e0r0
STUDYCOMPLETIONDATE
December 14, 1995
CHV Study No.: 17073-0-455
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00330
CORNING Hazleton QUALITY ASSURANCE STATEMENT
Project Title: In ivo Mouse Micronucleus Assay
Project No.: 20996
Assay No: 17073
Protocol No.: 455.
Edition No.: 17, Modified for 3M Corporation
pQruoajleicttywAesrseurcaonncdeucitnesdpeacctcioorndsoinfgthtoetshteudSytaannddarrdevOipeewroatfitnhgePfrioncaledruerpeosrotoftfhtheeQaubaloivteyrAesfseurernacnecde rUengiutlaatnidonasc.coFridnidnigngtso tfhreomgetnheerailnsrpeeqcutiiroenmseanntdsoffitnahlereappoprrtoprreivaiteewGwoeorde Lraebpoorrtaetdortoy mPraancatgiceement and to the study director on the following dates:
RandomizationofAnimals/09/18/1995 Draft report Review/10/31/1995 Final Report Review/12/14/1995
09/18/1995 10/31/1995 12/14/1995
S. Ballenger C. Orantes C. Orantes
Quality Assurance Unit
12/7 4
DaeReltased
CHV Study No.: 17073-0455
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CORNING Hazleton STUDY COMPLIANCE AND CERTIFICATION
RaTsehgesueltdaeftsoicrortnihsbiePndatrshtteu5Fd8oy,owidsassaunecddonDDderucucegtmeAbddemirinn2ci2os,mtpr1al9ti7ia8on,nc(e(efFwfDieAtc)hti,tvheTeiJtGuloneeo21d2o0fL,at1bh9oe7r9aU)t.oSwr.iytCPhroaadncetyoiacfpepFrleedgeurlaaltions saimgenneddmpernottso.colThtehartewwoeurlednaoffseicgtnitfhieciannttedgerviityaotifotnhsefsrtoumdythoeratfhoerienmteenrtpireotnaetdiorneogfutlahteiotnessitcorarebstluhelets. tTehstearratiwcldeaatsa hpraevseenbteeednhreerveiienwreedprbeysetnhtesSatnuadpypDriorpercitaotre,cwohncolucseritoinfiweistthhiant tthhee ceovnatleuxattoiofntohftehe study design and evaluation criteria. rAelclotredsthaasndbecoenntrroelvireeswueldtsbiyntthheisSrteupdoyrtDiarreectsourp.poArltledrabwy daantae,xpdeorciummeennttaaltidoant,a rreeccoorrddsa,npdrtohtioscol faancdilaitceospoyfofCotrhneinfignaHlazrelpeotrotngIennce.rfaotredatalseaasrtesounletoyfeatrhifsolsltouwdiynwgislubbmeisasrcihoinvoefdtihnetfhienaSltorreagpeo.rt to mattithmeeerS,ipoaorlnsssoerrnet.ttai0Anfeatdesrtiontrhtaehgeoensfetaocyirleaigaterypfdaeecrsiiilogidnt,easttheoedfSbCpyoomtnhsieonrSgpmoHanasyzolree.lteocnt Itnoc.hafvoer athneaadfdoitrieomneanltpieornieodd of Submitted By: Study Director:
Hemalatha Murli, Ph.D. DMeapmamratlmienatnoCfyGteongeetneitciacsnd Cellular Toxicology
Study Completion Date
CHV Study No.: 17073-0455
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TAOFBCOL NTEE NTS
CORNINGHazleton
SUMMARY
iii
10 SPONSOR oot
Page No. 6
20 2M1 ATECl(iTeeR nts'tsI AIrdteincAtlief)iLcation .......................oooo..............7 22 DateReceived 23 Physical Description 24 Genetics Assay No.
30 TYPEOFASSAY............ccooooiiiiiiiiiiii
40 PROTOCOLNO............ccooiiiiiiiiiiiiiiiiiiiiiiiii iT 50 5S1TUDYDAITnEitSia.ti.o.n.D.a.t.e...o.oooiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii il
52 Experimental Start Date: 53 Experimental Termination Date
60
SUPERVISORY PERSONNEL 61 Study Director
................ccccocoooiiuiiiiiil,..7
62 Laboratory Supervisor
70 OBJECTIVE ......ooiiiiiiiiiiiiiiiiiiiiiiiiieeeeee eT
80 MATERIALS .............................
veverssronnnis
90 SOLUBANIDLSTAIBITLITYY: ..............ccccoieee iii 8
100
DOSE SELECSTTUIDYON 10.1 DoseSelection
..............ccccciiunneniiniiiniinnnnill
8
102 Dosing Information
103 104
Results and Interpretation Conclusion
CHV Study No.: 17073-0455
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CORNINGHazleton
11.0 M111ICDRoseOSeNleScTtUiUoDnCY.L...E...U..S....ccccveeeeeenseiiiiiiienn. 10 12 Micronucleus Assay Dosing Information
120 BONEMARROWHARVEST,SLIDE PREPARATIONANDANALYSIS .....11
130 EVALUATION CRITERIA 13.1 General
................ccccceiiiiiiiiiiiiiiii 12
132 Data Presentation and Interpretation
140 RESULTSANDINTERPRETATION ....................................13
150 CONCLUSION .............ooiiiiiiiiiiiiiiiiiiiininnnnn 13
160 REFERENCES.................cooiiiiiiiiiiiiiiiiiiiiiii 14
170 EXPERIMENTDATATABLES ...................ccccceeiiiiiii1ii5i
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SUMMARY
CORNINGHazleton
Mutagenicity Test on T-6342 in an In Vivo Mouse Micronucleus Assay
`The objective of this in vivo. assay was to evaluate the abilityofthe test article, T-6342, `micronuclei in bone marrow polychromatic erythrocytesof Crl:CD-1%(ICR) BR mice.
to
induce
In the dose selection gavage at 500, 1625,
study,thetest article was solubilized in deionized water and 2750, 3875, and 5000 mg/kg. Six animals (three males and
dosed
by
oral
swiegrnes aasnsdi/gonremdotrotaelaicthy d. ose group. Animals were observed for three days after dostihnregeffoermatolxeisc)
>B5as0e0d0 omng/tkhge.reIsunltthseofmtihcreonduocsleesuesleacstsiaoyn,`tshtuedyt,estthaertmiaclxeiwmausmsotloulbeirlaitzeedddionsedewiaonsiezsetdiwmaatteerdaasnd
dosed by oral gavage at
were randomly assigned
t1o25e0a,ch25d0o0s,e/ahnadrv5e0st00ti`mmeg/gkrgo.upT.enVeahniicmlaelsan(dfipvoesmiatilvees
and fivfeemales)
control groups
euthanatized
with the test
aarptipcrloexwiemraeteeluyth2a4nahtoiuzresdaafpteprrodxoismiantgewleyr2e4,in4c8luadnedd
in
72
the assay. The animals
hours after. dosing for
dosed
extraction ofthe bone marrow.
`The test material, T-6342, did not inducae significant increase in micronuclei in bone marrow
polychromatic erythrocytes under the conditionsofthis `mouse bone marrow micronucleus test.
assay
and
is
considered
negative
in
the
CHV Study No.: 17073-0-455
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: CORNING Hazleton
Mutagenicity Test on T-6342 in an in vivo Mouse Micronucleus Assay
1.0 SPONSOR: 3M Corporation
20 MATERIAL (Test Article)
21 Client's Identification: T-6342 22 Date Received: July 21, 1995
23 Physical Description: Clear, colorless liquid
24 Genetics Assay No.: 17073 30 TYPEOF ASSAY: In Vivo Mouse Micronucleus Assay 40 PROTOCOL NO.: 455, Edition 17, Modified for 3M Corporation 50 STUDY DATES
5.1
Initiation Date: August 15, 1995
5.2 Experimental Start Date: August 29, 1995
5.3 Experimental Termination Date: October 16,1995 60 SUPERVISORY PERSONNEL
6.1 Study Director: Hemalatha Murli, Ph.D. 6.2 Laboratory Supervisor: Monica Vegarra, B.S. 70 OBJECTIVE
i`TnhdeucoebjmeicctriovenuofctlheiisininbovniveomaasrsrayowwapsoltyocehvraolmuaattiectehreyatbhirloictyytoefsothfeCtrels:tCaDr-t|ic1l%e,(ITC-R6)34B2R, to
mice. This study was Heddleet al. (1983).
conducted
`using
modificationsof the
procedures
suggested
by
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80 MATERIALS
`CORNING Hazleton
mRAiadvuxelirtmiLmzaabeloergaeatnnoerdtiifecse,hmeaPtloeerrtomagigecenee,MiLst.ty.raainTndhCiarstlht:ehCaeDls-th1ay%m,(eIrtCaiRnm)deoBamRs,sburwreeedrasectcrpeauisrnscwhtaoassaescdeolfemrcomtmoednChtsoarles dTohseinpgr.otocol for this study was approved by the CHV-ACUC pritoothre initiationouorfce.
c7Aa2ng4ie6maaltFsraawnndedro5mei5zhao1tu5isoe%nd.ruepsTtpheoectsitevevemlepyne.rpaeAtrucr1ea2ga-ehnodduurrreillnaigtgihqvtue/a1hr2ua-mnhtioiduniret,dyaarwnkedrcheyocmulaesiewndtaauipnetod fative per aAvaciolmabmleercaidallibdiitetum(PfuorritnhaedCuerrattiifoineodfLtahbeorsattuodyr.y PTehlleetfseed#w5a0s02a)naalnydzewdatbseyrmtawhieenrteained. rhmeyatdnrruoofscapacerctbtuiorvneesr,bfaoosrrigscaonfnoocrpehsnoptesrcpaihtfaiiotenedsso,mfiascpnredocosirpfgeiaceniidfishemedsa,nvupytersmiteeintctaisld.se,sT,ahfaellakwtaoalxitinenir,tywc,hahlseoraainnaaltyezded on a ahnaliomgaelnss.or Swaonriktiinzegdwciatghiinngtwheasanuismeadl ffoarcihloituiseisnwgertheeraeniqmuailsr.etodPewresaornnseuiltahbavlnyedlmpireonttagelcst,ivaen.d `garments and equipment.
arAnaninimdmaoalmlslsywweaersreseidgqonuseaedrdatnbotaissnteeudddyufpogorrnosuetpvhsenainnbddeifwvoeirdreueableiinbdnoigdvpiyldauwaceleilgdyhotwnse.sitgAuhndeyid.mapArlnisoirwmeatorlesdouwsneiinrqge.uelAyll identified by ear tag. Dose or treatment groups were identified by cage card/label, iAnthatlhaetitoenr,mifnoaltlioownedoftbhyepesnteutdryataillonosufrtvihveintghoarnaix.malAsnwyeerxetreautahnainmaatliszendotbyusCeOd,for the study were cuthanatized by CO, inhalation, followed by penetrationofthe thorax. 90 SOLUBILITY AND STABILITY:
The this
atsesstayarwtiacsle,deTi-o6n3i4z2e,d
wwaatsers.uppTlhieedstaasbialictlyoeafrtchoelotrelsetssmaltieqruiida.l
uTnhdeervethhiecldeossienlgected
for
conditionsofthis assay is the responsibilityofthe sponsor.
10.0 DOSE SELECTION STUDY
10.1 Dose Selection
`Dgoasveagelefvoelrstohfe d5o00s,e s1e6l2e5c,ti2o7n50st,ud3y8.75, and 5000 mg/kgwereadministered by oral
CHV Study No.: 17073-0-455
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CORNING Hazleton
102 Dosing Information
wa`eTnihdgeh2a1tn.ri1amna-gl2es5o.u1fstegdhraeimntsah,niefmdoaorlstsheseuesmleaedlcietnsitohanenddaosfsseaemyawlreeasrn,geerdeofsispneedcditniovgnealysA.suagyuDoswstais2n92g,6s.1o59l9u-5t3.i3o.nT5she `swteorcekfporretphareedhijguhstdporsieor(5to00d0osmign/gkga)n.d wTehrise pwraespparreedpabryedmbay akddi2inn5g0g60.6mgm/lmolf cdleeiaorn,iczoeldorwlaetsesrso(lLuottio#n.17,Dpirluetpiaornesd oafttChiHsVs)totcok6w.e0r0e07prgoepfarTe-d63f4or2,threeostuhletirndgoisn ea levels
wDeoeskinsganwdasonaechdiaeyveodldusaitntghea t1i0mmeol/fkdgosdionsgi.ngAvnolouumteli.neAolfltahneimdaolssinwgersechceigmhetis found in the following table.
A totalof 30 animals was used in this assay.
TREATMEDNOTSE GROUPS MF
T-6342 500 mg/kg 1625 mg/kg 2750 mg/kg 3875 mgkg 5000 mg/kg
303 303 303 303 ER
All doses given were on an acute (one-time only) bass. 103 Results and Interpretation
sAtludayn(itmharlese wdeayrse)efxoarmtionxiecdeafffteecrtsdoasnidn/goranmodrtdaaliiltyietsh.roAulglhaonuitmtahlesdauprapteiaorneodfthe onbosremravlatiimomnepdeiraitode.lyTahfteermodrotsailnigtyanddatraefmoaritnheids ahsesaalythayreunstiulmtmhaerieznedodfitnhtehe following table:
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CORNINGHazleton SuimnmMaircyeoDfosMeordtAacliuttieelsyWwiitthhiTn-363D4a2ys
Observations
500 mg/kg 1625 mg/kg 2750 mg/kg 3875 mg/kg 5000 mg/kg -_-- 104 Conclusion
03 3
03 3
3 03
03 3
3
03
OOO
Based >5000
on these mg/kg.
results,
the
maximum
tolerated
dosewas
estimated
to
be
11.0 MICRONUCLEUS STUDY
111 Dose Selection
5B0a0s0edmogn/krgewsuelrtsesferloemcttehde
dose selection for this study.
study,
dose
levels
of
1250,
2500,
and
11.2 Micronucleus Assay Dosing Information
CTyhcelaonpihmoaslpshuasmeiddein(tShiegmmai,crLoontuc#l4eu3sH0a2s6sa9y,wCeArSe d#os6e0d55o-n19S-e2p),tetmhbeepros1i9t,iv1e995. cwoanstraodlm,iwniesstseorleudbiblyizoerdalignasvteargieleadtei8o0nmigz/ekdg.watTehre(Lvoethi#c1l7e,cpornterpoalr,eddeaitonCiHzVed) and amwriatctirecolren(uaLtcolate#uvso1la7us,mspaeryeowpfaa1rs0ed2m8la./t7kCg-.H3V7)T.,h6ewgawaesnidagdh2mt1i.rn1aisn-tg2ee5or.fe6td hgcoegnrcaaunmrirsmeafnlotsrlyutshweeidmthailntehtseheatensdt amfdeadmkaiilnneggs,daeri5eos0np0iezcmtegidv/ewmlaylt.esrtTothcoek1fd1oo.rs0it0hn0eg8hsgiooglfhuTtd-ioo6ns3se4f(o25r0ut0ph0etmoagsa/skavgyo)lw.uermTeehoipsrewpaasrepdrebpyared by tchleearr,emcaolionrilnegssdososleutlievoenlsw.as obiained. Dilutionsofthis stock wefre22p.r0epmalr,edAfor
CHV Study No.: 17073-0455
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CORNING Hazleton
hTaernveasntitmiamles g(rfiovuep.malVeehsiacnlde afinvdepfoesmiatlievse)cwonetrreolragnroduopmsl,yeaustshiagnnaetdizteodeach dose/-
dapopsreodxwiimtahtetlhye 2te4sthoarutrisclaefwteerrdeoesuitnhga,nwaetrizeeidnacplpurdoexdiimnattheelyas2s4a,y.48Tahneda7n2imhaolusrs
after dosing for extraction ofthe is found in the following table:
bone marrow.
An
outlineofthe
dosing
scheme.
Dosing Scheme for Micronucleus Assay
A totalof 110 animals was used in this assay
NumberofAnimals Assigned
Treatment eZ
1250 mg/kg
2500 mg/kg
5000 mg/kg Vehicle Control, dei1o0nimzeidgwater _P--ositive Control, Cyclophosphamide, 80mghkg
2M4FH 4M8FHr TM2HFr
55 55 55 55 55 55 55 55 5s
55... 55 - - - -
TVhoeluamgee odfostehde awnaisma1l0smalt/tkhge atnidmewofadsobsaisnedguwpaosneiingdhitvwideueaklsaannidmaolnweediagyh.t,
120 BONE MARROW HARVEST, SLIDE PREPARATION AND ANALYSIS
pAetnetthreaatpipornoofprtihateethhaorrvaexstantdimteh,etahdehaenriimnaglosfwtetriesseuuethaanndateipziepdhywsietshoCfOb,otfholfleomwoerdabwyere croenmtoaviendi.ngT3h-e5mamlrrboowviwnaessfelruusmhe(donferotmubtehefobroenaechanadnitmraaln)s.ferFroeldltoowicenngtrciefnutgreiftuugbaetsion to pweelrleetstphreeatidssoune,sltihdeessuapnedmaaitradnrtiewda.sTrheemoslvieddesbwyearsepifriaxteidoninamnedtphoarntoilo,nsanofdthsteaipneeldleitn cMoavye-rGslriupnpweadludsisnogluDteiopnexfolmloouwnedtibnygGmieedmisuam.(Schmid, 1975). The air-dried slides were
eTrhyethsrloicdyetsew(ePrCeEc)odtoednofromroacnahlryosmisa,tiacndersyctohrreodcyftoer (miNcCrEo)nuccelleliraatniod.thSetapnodlayrcdhrfoomramtsicwere
CHV Study No.: 17073-0455
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00340
CORNING Hazleton
mPuCisEceSrdsotnpourcreleseceaonrttdeidtnhcteehlselessdwcaoatars.edeOxopnpreteisctshfeoideulsda.asnpdTehrPecCeEnntoSrmpmieacrlraofnnriuecmqlaueleanwtceeyrdoecfesmlciloscrrebodan.suecTdlhoeeinfitrheeqtuoetnacly of
Crl:CD-1%(ICR) BR strain is about 0.0-0.4%.
n this
TNhCeESfroebqsueernvceydofinPtChEesopvteircsfuiselNdCsEwhsilweasscdoertienrgmtihneedfirbsyt 1sc0o0r0eirnygtthhreoncyutmebse,r of PCEs and 13.0 EVALUATION CRITERIA:
13.1 General
MTihcerocrniutcelreiaifwoerrtehedairdkelntyifsitcaaitnieodnoafndmigcernoenruaclllyeirowuenrde, tahlotsheooufghSaclhmmoindd(a1n9d76)
rainndgwshearpeegdemniercarlolnyucbleetiwoececnas1i/o2n0alalnydo1c/c5urtrheeds.izMeoicfrtohneucPlCeEi.haTdhsehaurniptobfosrdceorrsing
mwoarsethtehamnicornoenumcilceraotneudclceeluls, nwoatstchoeumnitcerdoansucolneeusm;ictrhounsutchleeaotcceadsiPoCnEa,l ncoetlltwwioth(or
more) micronuclei. of PCEs and NCEs
(Tbhleuisstha-ignrienyg apnrdocreeddu,rreesppeercmtiivtetleyd).the
differentiation
by
color
13.2 Data Presentation and Interpretation
DInadtiaviadrueasluamnmiamrailzdeadtabyarseeaxlsaondprdesoesnetegdr.oupTshefoarnatlhyesdiisfoffetrhenetsteimdeatpaoiwnatss. p(ewrhfeonrmvaerdiaunsciensg aarneahnoamlyosgiesonefovuasr)iaanncder(aWniknetrr,an1s9f7o1r)meodn(ewihtheenr uvanrtiraanncsefsoarrmeed hofetvearroigaennceeowuas)s psriogpnoifritciaonntso(fpc<e0.l0l5s),wiatDhumnincertot'nsuctlteeistpe(rDuannniemtatl,. I19f5t5h;e 1a9n6a4l)yswias s unesgeadttiovedceotnetrromli.ne Awnhailcyhsedsosweergeropueprsf,ioframneyd,sewpearreatseilgyniffoirceanatclhy hdairfvfeesretnttifmreoamntdhe ssteaxticsotimcbailnlaytsiiognni.fiTcahnet cdroistee-riraelfaotreddeitnecrrmeiansienignamipocsriotniuvcelreeastpeodnPsCeEiSn,voolrvethdea dleeatsetctoinoen doosfaerleepverlo.duAcibtelset aanrtdicslteattihsatticianldlyucseigdnnifeiictanhteaprosstiattiivsetircealslpyonsisgeniffoircaatnt dleovseel rweasspocnosnesindoeraredstnaetgiasttiivcea.llyIsnigeniitfhiecracnatsae,ndthreepfirnoadlucdiebcliesiionncrweaassebaatseodneondose scientific judgment.
CHV Study No.: 17073-0455
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00341
140 RESULTS AND INTERPRETATION:
CORNINGHazleton
adAunlrldaaptnoisioinmtaoilvfsetwcheoenratesrsooalbysgefrroorvueptdosxiaimcpmpseeydaimrapetdteonlmoysramafatnledra/fodtroesmrionrdtgoaslaiinntdgiepsae.nrdiAordleimcaaanliilnymeadtlhshreoianulgtthhhoeyutvuenthhiecle aappppreoaprreidatneorhamravlesitmmteimdeisa.teAllylaatneirmadlossifnrgoamntdhere1m2a5i0neadndhe2a5l0t0hymngi/klgtdhoesaeppgrroopurpitsaitlethe harvest times.
Immediately after dosing, all animals in the 5000 mg/kg dose group appeared normal, hAopuprrohxairmveasttelgyro2u4p)hofurrosmatfhteer5d0o0s0inmgg,/2kgmadloesse(g#r'o52u7p1w2,er4e8fhoouunrdhdaeravde.stOgnroeump;al2e714, 72. a(n#i2m7a1l8s, a7p2pheoaurerdhanrovremsatlgratoutphi)satpipmee.ared hunched and weak with squinted eyes. All other
fAepmparloexi(m#a2t7e80l,y 7428 hhoouurrshaafrtveerstdogsrionugp,)|fmraolmet(he2751080,0 7m2g/hkogurdohsaervgerstougprowuepr)eafnodun1d dead.
Al otheranimals harvest times.
appeared
normal
at
this
time
and
remained
healthy
until
the
appropriate
opTrohleaytctaehnsrtyooamfratttichilcee,ehrTay-rt6vh3er4sot2c,yttiiemnsedsou.vceeDrdutnhtoeoslietgvonexilifsciicotabyn,stetrihnvecerPdeCaiEsne/tshNeiCnvEmeihrciacrtloieonsuoccoflntetrahotelesdmailn eesitahnerd sex
lfoewmearletshafnrotmhethveeh5i0cl0e0cmognt/rkogl daonismealgsr.oupThaet tphoesi7t2ivheocuornthraorlv,eCstP,grionudpucweedresisginginfiifciacnatntly
increases in micronucleated means and standard errorsof
5P.C4Es4%in=bo0t.h37s%eaxensdas2c.o5m0p%a+re0d.3to3%thefovrethhieclmealcoenstraonlds,
with
ifnedmiavliedsu,alreaspneicmtailvedlayt.a aTrheefdoautnadsiunmTmaabrliezse2dtbhyroduogsheg7r.ouHipsatorreicparlesceonnttreodlidnaTtaabalree 1 and
presented in Table 8.
150 CONCLUSION:
nTmeahgreatttoievswtepmioanltteyhrcieharmlo,omuTas-t6ie3cm4ei2rc,yrtdohinrduoccnlyoettueissnaudsnusdcaeey.ratshiegnciofnidciatnitoinnsocfretahsiesiansmsiacyroannudcliseicoinnsbidoenreed
CHV Study No.: 17073-0455
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600342
160 REFERENCES:
CORNING Hazleton
aDcuonnntertotl,.C.JW..A:.m.AStmautlitsti.plAesscoomcp,a5r0i:s1o0n9s6-p1ro1c2e1d,u1r9e5f5o.r comparing several treatments with
Dunnett, C.W.: 491, 1964.
New tables
for multiple
comparisons
witah
control.
Biometrics,
20:482-
aHnedddSlael,aJm.oAn.,e,HiMt.eF,.M:, ThKieriknhdaurc,tiBo.n,oLfarmsiecnr,onKu.,clMeaicaGsreagmoera,suJ.rTe.o, fNegweenlolt,oxGi.ciWt.y. MutationRes., 123:61-118, 1983.
Schmid, W.:. The micronucleus test. Mutation Res, 31:9-15, 1975.
MSucthamgiedn,sW:.:PriTnhceipmliecsraonnducMleetuhsotdesstffoorrTchyetiorgeDneetteicctiaonna,lyVsoils..
Chemical 4 (A. Hollaender,
ed). Plenum, pp. 31-53, 1976.
YWoirnke,r,SBe.cJo.:ndStEadtiitsitoinc,al
Principles 1971.
in
Experimental
Design,
McGraw-Hill,
New
CHV Study No.: 17073-0455
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00343
`CORNING Hazleton 17.0 EXPERIMENT DATA TABLES
CHV Study No.: 17073-0455
1s 00344
CORNINGHazleton
SPONSOR: 3 Corporation TEST ARTICLE:T-6342
MICRONUCLEUSTDAABTLAE S1UMMARY TABLE
ASSAY:17073
TREATMENT cowaoLs
vEIGE TOSTIEGE
DOSE HATRIVNEEST (Rr)
acer
Wh
80.0 mk he
MEAN O*%FMI1C0R0O0NUPCELREAATNEIDMALPC%EsS.2.
aes
FEMALES TOTAL
RAMTEIAONPCE5:.NEC.E MALES FEMALES
oaisom 542037
0-0220.02 1302003
oonto.oz | 0s1to.0s amiose | cette
0.520. oe sens
TT ARTICLE 1250 make he "hr
7h BO ml he
"wh he
000 make he "wn nr
0.284 0.05 0.000.00 oossom 0.022004 cmon omen 0.0620.06 custo ose
0.002000 0.0220.02 e-0120.02 0.0020.02 .0220.02 o0620.00 0.0020.04 0.062002 0.032000
oa420.05 | 049x000 0.10.01 | 0.68 to.0n ooe20.0: | 0360.08 0.0020.02 | 0.6920.07 0.0220.01 | 0.7920.00 omzo0 | ourzo.0r 0.0020.03 | 0.00%0.08 0.1020.00 | o36%0a0 0.0920.03 | 0720.04
07s sour 0.74 0.08 0.3920.08 0.602008 ous 20.01 o.6to.0 0.75 0.00 0.63% 0.08 0.2620.050
"Significantly different from the corresponding vehicle sentrel. pO 0%
CHV Study No.: 17073-0455
16 00345
`CORNINGHazleton
MICRONUGLEUS TEST T-ABILNEDI2VIDUAL ANIMAL DATA SPONSOR3:M Corporation
TEST ARTICLE:T-6342
HEASSAY No.:17073
ANDHAL vaad TIO
_ SREASHENT TnUumer(lPoSoEpe) FOEpcNpNinCcEe
_--
VERICLE CONTROL acer.
wwee 3 00.3342
EwmHaw 21
ooslea ost
POSITIVE CONTROL CP 80.0 mks 9 ae u61s 00.5709
m ms asz nw
oeste os
Test rier 0 aks ww wre d34 0o0.7s6s87
m ma 33 boeigs
m0 wk wwes 21 o[l
Hmnei o2 0B0e.7920
FR. we oo 0.51
_-- Fm wSs o1 7pasee
NoPCMEN= PPCoMENlsyc==hrMNoiimccarrtooinncuucclelereuyasttherdocFyEteS
NCE=Normochromatic erythrocyte
CHV Study No.: 17073-0455
00346
1"
`CORNINGHazleton
nrcRowcLeus Testa"nTepiv3iouaL ANIMAL baa
SPONSOR3:M Corporation
TEST ARTICLE: T-6342
CATssayewwo.i170rmer73
momoemn PCOBE s pmmCo
--__--o--m csr rs
(000) PeE:NeE
I --------
ma oe s oor oooonnnne
osm coma
woe mis
mos me ow
om
Ben ol
mans we wm FFaErso ae
Bo wm
moo mwmoe0 aas
m FFHH odu
wx Fo wHe s0 oenm
e _-- e m ae oaal
NPWGEoE N=oPrPmC0ooSlcyhc=+ehoWiWoimincseertrtoioimcmeuceeilareesynnyseeshehrdooccByyetoee
CHVStudy No.: 17073-0-455
00347
18
: `CORNINGHazleton
SPONSOR3M:MICRCOoNrUpCoLrEaUtSionTEST T-ABILNEDI4VIDUAL ANIMAL bATA
TEST ARTICLE:T-6342
ASSAY No.:17073
TREATIES
hAomza TPOCEE GaEAnTsIC
oo oun waver ace
Test aamzeus _--
we wa soo akg 000 mung
s nm0oo oo0 ooondut
FmEao on44
mwwees o oo on n0.51
Ea E o In H
EwFHrr
oo0le.
omei 5 oh
NPoCMEN= CP"EoMASlYnyic=m=harliMoeeimccafrotooniuncunudccelirdeoyeastathderdoc0ytse NCE-Normocheomatic erytheacyie
CHV Study No.: 17073-0-455
00348
19
`CORNINGHazleton
wicRowcLzvs Test maHabv5inuL aviv oan
SPONSOR: Corporation
Test AnTroLE T6242
T ASSAYEA0.Tr 1E1N7073 eme Mek r foze e TIO
_ J-P_-- ------
(ooo)"NE
-- 202 = oWYy= HnicraonaciTEeotnhRsroc3 yte NE om GeeR Cae
CHV Study No.:17073-0455
00349
20
`CORNING Hazleton
WICROWUCLEuS TEST asReBIVIOUAL ANIMAL DATA
SPONSOR3:H Corporation
Test AntroLET6302
ASSAY wo.117073
--_-- EATEN
MowmgTsAR PoLze y(rATaIC
e on wa mas o (logy) PCE:NCE
ee "Animalce rfouond ndseeane d NPRCoeEEhm=noFproomlReycahhenR mmaerciies sayrY oaheraoccryctse
CHV Study No.: 17073-0455
00350
21
`CORNINGHazleton
wicRowcizus Testm"anTHeDIVIDUAL ANDHAL DATA
SPONSOR3:M Corporation
TEST ARTICLE T6342
TACSSAmTYReEwoAm.T:Ie1E7Se073
mNommex PCOEBs SmTmE
_ I _-- ---- 0(100000)0POE:NCE
mEATEE 0 wm emmeoofs0 oeae
E eoEs om
we wk Fmmreos1 oenw
m moososoa
0 wa Ro mmS s0 ea
e _-- eE Wn O E ew
NETCH+ Pe"EAlSnyicn=haNilicosenviffotoniumutned]agndaeyecsaedhersocVyetee
RCENormachepaatie aryhencr
CHV Study No.: 17073-0-455
00351
22
.
`CORNINGHazleton
TABLE 8
MOUSE MICRONUCLEUS HISTORICAL CONTROL DATA 2/95 THROUGH 9/95
%
MWEIACNRONOFUCL1E00A0TEPDERPCAEN:IMpAerL
1000 PGE * S.2.
RATIO FCETNCE MEAN 5.2.
TooLEd vanzoLr cowrRaL
MALES FEMALES TOTAL MALES FEMALES
Ed ax AVG
0.00 0.26 0.08 0.05
0.00 0.16 0.06%0.04
0.01
0.32
0.18 0.0720.04
|
0.82 0.56 0.43
0.3 1.08 0.61% 0.14
"
"
"
"0
"
CryocslzoTpahvoespchonaTnRiodre.. 0 mg/kg.
a 12 x 5.46
1.30 6.36
10 3.8
0.44 0.72
0.4 0.01
AV n
3.252094 2
3.002105 2
3320.81 | 0.58 0.00
a
a
0.62 20.1 2
CHV Study No.: 17073-0-455
00352 23