Document 8kdKmd576226byQz1bxDN52m
ARM6-OU30
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CORNING Hazleton
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MUTAGENICITY TEST ON
g-CEl[l 2
T6564
==
IN AN IY F170 MOUSE MICRONUCLEUS ASSAY |: NOV 05 1296
[EINALREPORT
Licons
AUTHOR Hemalatha Murli, Ph.D.
EREORMING LABORATORY
z
`Corning Hazleton Inc. (CHV)
9200 Leesburg Pike
Vienna, Virginia 22182
LABO PRR OJECA T IDT ENTO IFIR CATY ION CHV Study No.: 17750-0-455
SUBMITTTEOD
: pe meres ronson i
3M Corporation
:
`Building 220-2E-02, 3M Center
STUDY COMPLETION DATE November 1, 1996
CHV SyNos. 177500455 :
Lots
`
00176
:
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`CORNING Hazleton
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QUALITY ASSURANCE STATEMENT
Project Title: In Vivo Mouse Micronucleus Assay
Project No.: 20996
Assay No.: 17750
Protocol No.: 455
Edition No.: 17, Modified for 3M Corporation
Quality Assurance inspectionsofthe study and reviewofthe final report ofthe above referenced Unrperigoutjleaactntidownesar.cecoFcriodnniddniugncgt(s0edfthoaecmgceotnrhederiainlngsrtpeoeqctuthiieroenSmsteaannntddsarofdifntOahpleerreaapptopirrntogprrePivraioteceweGdwoueroredesoLrfaetbphoorenaetQdouratlyoimPtrayancAatsgisceuemreanncte and to the study director on th folowing dats:
Inspection/Date
FindingsReported Auditor
Dosing/07/30/1996
073011996
C. Orantes
Harvesu08/1/1996
08/1/1996
C. Smith
Draft Report Review/09/17,18/1996
0918/1596
C.OrantesC. Smith
.
Final ReportReview/1 1101/1996
111011996
C. Smith
Fe
lity Assurance Unit
/i)58.
Date Released
CHV Study No. 17750-0455
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STUDY COMPLIANCE AND CERTIFICATION `aTshseetdefsocrrtihbiendtshteuFdyoowdasancdonDdruucgteAddmiinnciostmrpaltiiaonnce(FwiDtAh)tThietlGeo2o1dofLatbhoeraUt.oSr.yCPordaecotifceFreedgeurlaaltions `Raemgeunldamteionntss.PaTrthe5r8e, wisesuredneoDesicgenmibfiecran2t2d,ev1i9a7t8i,o(nesfffercotmivtehJeuanfeo2r0e,me1n9t7i9o)newditrhegaunlyataipopnlsoicratblhee s`Tihgenerdawprdoattoacohlavtehatbeweonulredvaifefweectdtbhye tihneteSgrtiutdyoyfDtihreectsotru,dwyhoor tcheertiifniteesrptrheatattihoenoevfatlhueattieosntorfetshulets. stetsutdayrtdiecsliegansapnrdeseevnatleudathieorneicnrirteerpirae.sents an appropriate conclusion within the contextofthe
rAelclotredsthaasndbecoenntrroelvireeswueldtsbiyntthheisSrteupdoyrtDiarreectsourp.poArltledrabwy daantae,xpdeorciummeennttaaltidoant,a rreeccoorrddsa,npdrotthoicsol
afancdiliatcieospoyfofCothminfginHaarzelpeotrotngIenne.rfatoedatalseaasrteosnuletyofetahrifsolsltouwdiynwgilslubbmeiasrscihoinovefdthien tfhienaSltorreapgoert to
i
tmhaeteSrpioanlssorre.taiAnfetderinthteheonseoryaegaer pfearciiolidt,etsohefSCpoomnisnorgmHaayzleelteocnt tInoch.afvoer tahneaadfdoirtieomneanltipoernieodd of
1
time,orsent10astoragefacilitydesignatedbythe Sponsor.
!
Submitted By:
Study Director:
Nout tue .
M`HaemmmaalaltihaanMCuyrto,gePnhe.tDi.cs
Deparment of Genetic and Cellular Toxicology
uid
Study Completion Date
CHV Study No.: 17750-0455
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TAOFBCOL NTEE NTS PageNo
SUMMARY ooo
6
10 SPONSOR oii
20 2M1 AClTienEt(sTRelsdteIAnirfiAicclaLi)o.n 2232 PDhaytseiRcealcDeeisvcerdiption 24 GeneticsAssay No.
een T
30 TYPEOFASSAY ooooiiiiiiiiiiiieeeeee eT
:
40 PROTOCOLNO. .....ouuviiiiiiniiiii ieee
T
:
50 S51TUDYInDitAiaTtEioSn Date ce tarrrsrsssarie sesnrsrossstoacd
5532 ExEpexrpimeerntialmSTeteanrnmtiDnaaattleion Date
60 6S1UPERSVuIdSyODRiYrePctEoRrSONNEL .............0vrririnrnsrniin]
1
62 Laboratory Supervisor
.
70 OBJECTIVE ...o.oiiiiiiiice eT
80 MATERIALS ...........oooiiiii iii
8
90 SOLUBANIDSLTAIBITLITYY ........ cocsrsrusn sossererasad
::
100 D1O01SEDSoEsLeECSeTlIecOtNionSTUDY .
crt shepractstsassas sassnsssanel
:
110032 DoRsiengasInnfdouIrnmtaeltriportentatsion
104 Conclusion
CHVStudy No.: 17750-0455 i
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11.0. DOSE SELECTION STUDY! .. ILI DoseSelection
en
112 Dosing Information
113 114
RConcelusasinodnuIntelrprietatsion
. nn
120 MICRONUCLEUS STUDY 12.1 DoseSelection
.........cooiniiiiiiieinee e153
122 Micronucleus Assay Dosing Information
13.0 BONEMARROWHARVEST, SLIDE PREPARATIONANDANALYSIS ........ 14
140 E14V1ALUGAeTneIrOalNCRITERIA ......ooviiiniiiiiiiieniieee 142 Data Presentatainodn Interpretation
LL 1S
i
150 REAS ND IU NTERL PRET TATIS ON .................cc............... 16
160 CONCLUSION ........ooiiiiiiiiiiiiiiiiiii cece
16)
17.0 REFERENCES..........oooiiiiiiiiiiiiiiiiieiineeee ee 17
18.0 DEVFRI OMTA HESIT GNEI DPRO OTON COL ................ooernnnn... 17
190 EXPERDIATMATEABNLETS ................cccooireeiiiiieeii 18
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SUMMARY
Mutagenicity Test on T-6364 in an In Vivo Mouse Micronucleus Assay
:
``Tmhiecroobnjuecclteiiveion fbtohniesmianrvriovowapsoslayycwharosma1t0iec veryathlrtohucyetaaebsiotlifteyCorfl:tChDe-t1est(aIrtCiRc)leB, RT-m6i3c6.4, 0 induce
gTnatvheagdaoetse10s0e0l,ect1i5o1n0,st2u0d1y0,,t2he54te0satnadrti3c0le10wmags/skolguibnilaifzeidirnsrdietaliaonnidztehdewnatdeorseadndatdo1s0e1d0,by15o2r0a,l aa2sn0sd2il0go,nraemndodrtao2l5ci3atc0yh.mdgo/skeggrinou2sp.ecAonnidmarlaslw.erSeixobasneirmavlesd(ftohrrefeoumraldeasysanafdetrhrdeoesfienmgafloers)twoecresigns
aBbaosuetd 2o0n00themgr/eksgu.lsoIfn tthheemdiocsreonsueclelcetuisonassstauyd,yt,hthetemstaaxritimcluemwtaoslesroaltuebdildiozseed wian sdeeisotniimzaetdedwaatser
:
afenmdaldeoss)edwebryeorraalngdomalyvaaasts4gi9g8ne,ed9t9o5,eaacnhddo1s9e9/0hamrgv/eksgt.tiTmeengraonuipm.alsVe(hfiicvelemaanldespaonsidtifvievecontrol
gdroosuepds,wietuhthtahneitzeesdt aarptpircloexiwmearteeleyut2h4anhiozuerdsaapfptreorxdiomsaitnegl,yw2e4r,e4i8ncalnudde7d2ihnotuhresaasfsaeyr.doTshienganfoirmals
extractionofthe bone marrow.
`pTohleyctehsrtommaatteirciaelr,ytTh-r6o5c6y4t,esdiudndneort tihneduccoendaitsiiognnisofifctanhtisinacsrseaayseanindmiisccroonnsuicdleeriedinnbegoanteivmearinrotwhe `mouse bone marrow micronucleus test
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Mutagenicity Test on T-6564 in an Jn Vivo Mouse Micronucleus Assay
10 SPONSOR: 3M Corporation
20 MATERIAL (Test Article)
21 Client's Identification: T-6564 L-13167 FC1015-X
22 Date Received: May 30, 1996
.
23 Physical Description: Clear colorless liquid
24 GenetesAssay Noa 17750
3.0 TYPE OF ASSAY: In Vivo Mouse Micronucleus Assay
40 PROTOCOL NO.: 455, Edition 17, Modified for 3M Corporation
50 STUDY DATES
5.1 Initiation Date: June 4, 1996
52 Experimental Start Date: July 11,1996
53 Experimental Termination Date: August 22, 1996
#
60 SUPERVISORY PERSONNEL
6.1 Study Director: Hemalatha Murli, Ph.D.
62 Laboratory Supervisor: Monica Vegarra, B.S.
i
70 OBJECTIVE
`The objective of this in vivo assay was to evaluate the ability ofthe test article, T-6564t,o
Hmiinecddeud.cleeTmheitiacslr.osnt(uu1cd9ly8e3wi)aisn cboonndeumcaterdrouwsipnoglmyocdhirfoimcaatticioenryotfhtrhoecytperso.ocefduCrrels:sCuDg-g1e%s(tIeCdRb)yBR
CHVStudy No: 17750-0455
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80 MATERIALS
ARidvuelrtmLaabloeraatnodrifees,maPloermtiacgee,, sMIa.inThCirs:hCeDal-t1h%y,(IrCaRn)doBmR,brweedrseapiunrcwhaassesdelfercotmedCthoarles "mTahxeipmriozteocgoelnfeotricthhiestsetruodgyenweaitsyaapnpdroavtetdhebsyatmhee CtiHmeV-asAsCurUaCccpersisoooatcheominmitoinatisoonurocfe. dosing.
r5A5a.n2nidmoam1li5sz%a,wteirroeensp.hecoTtuhisveeedltyef,mipveeexrcpaeteputrcoeangaeJnuddluyrrei3ln1agt,iqv1ue9a9hr6ua,mntifidonriett,yhaewndederfehionmiuatsiienvdetafsiitnvuedeydp,earwth7cea2gneta6hteF aod
chuommimdeirtcyiwalasdireetc(oPrudreidnaas C7e5r.t1i%f.iedALa1b2o-rhaotuorrlyiPghetll1e2-thso#ur5d0a0r2k)caynedlewawtaesrmwaeirnteaianveadi.labAle
:
caodncienttruatifoonrstohfe sdpaetciifoiendohfetahveysmueddyal.s,Tahfelafteoexdinw,acshlaonrailnyatzeeddhbyydrtohceamrabnounfsa,cuures for organophosphates, and specified nutrients. The water was analyzed on a rerospective
i :
Sbaansistifzoerdscpaegciifnigedwamsicursoeodrgfaornihsomuss,inpegsttihciadnesi,maallsk.aliPneirtys,onhneealvhyamnedtlailnsg, aannidmahlalsoogerns. working within th animal facilis wre required to wear suitable protective garments
and equipment
rAannidmoamllsywaesrseigqnueadratnotisnteuddyfogrrosuepvsenanddaywsebreefionrdeibveidiunagllpylawceeidgohnedstpudryi.or tAondiomsailngs.weArlel
aidneinmtailfsiewd ebrye adrosteagd. baDsoesdeuoprontrtehatmienndtigvridouuaplsbwoedryewiediegnhtisf.iedAnbiymcaalgsewcearredluanbieqluely
:
iAntthaleattoenr,mifnoaltlioownedofbtyheCOst,udiynhaalllastuirovniavnidngpaennietmraaltsiowneorfetehutthhoarnaxi.zbeAydnyCOexytOra;animals
not used for the study were saved orGaining
:
90 SOLUBILITY AND STABILITY
:
tThheetetsetstaanrtciclle,waTs-6c5a6l4c,ulwaatesd siunppthleietdeastia ng cllaeabrocroalotrolaressys 1l.i2qu2idm.l.TheThsipsecsipfeiccifgircavgirtayviotfy
wtiahnishsuiasssesaadsysatayo.npdrTethpheaertedeesdttoeasrniminicgnlaesttciohocankorsafcfttoerhtrheistteiscatssaasacy.deefDisenteiadboinliiinzttyehduenwGdaeLtrePrtrhweeagdsuolusasitienodganscoonftdhiFetDivoeAnhsi(co2l1fe
rCeFspRon5s8i.b1i0l5t)y, oEPtfhA-TspSoCnsAor(.40 CFR 792.105), and EPA-FIFRA (40 CFR 160.105) the
CHV Study No: 17750-0455
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10.0 DOSE SELECTION STUDYI
10.1 Dose Selection
gDaovsaegelefvoerlstoheff1i0rs0t0,do1s5e10s,el2e0c1ti0o,n2s5t4ud0y.and 3010 mg/kg were administered by oral 102 Dosing Information
TThheeawneiimgahltsruasnegde oifntthhee afinristmadlosseusseeldeicntitohneadsossaeyrwaenrgeedfoisnedidngonasJsualyy w1a1,s1996,
s3o0l.u9t-i3o5n.s1 waenrde2p2r.e2p-a2r7e.d6 jgursatmpsr,iofrortothdeosmianlgesanadndwefreemaplreesp,arreesdpebcytimvaelkyi.ngDoasing
.
3de0i1onmigze/dmwastteorckf(oCrHtVh,eLhoitg#h d1o9)seu(p3001&0mvgo/lkumge).ofT1h5i.s0wmais1p0r.e3.p7armeldobfyTa6d5d6in4g, resulting in aclear colorless solution. Dilutionsofthis stock were prepared for
i
the 2540, 2010, 1510 and 1000 mg/kg dose levels.
wDeoeskisngawnadstharceheiedvaeyds uolsdinagtath1e0timmle/okgfddoossiinngg.voAlnumoeu.tliAnleloafntihmealdsoswienrgesecihghetme is found in the following table.
Dosing Scheme for Dose Selection Assay I
:
--TrTe65a6m4em 1000 mg/kg
Male Female 50s
1510 mg/kg 2010 mghkg
33 3
2540 mg/kg 3010 mg/kg.
3s 35
A(onteo-tuiomfe 3on0layn)ibmaasliss was used inthis assay. All doses given were on an acute
103 Results and Interpretation
sAtluldayn(ifmoaulrsdwaeyrs)e efoxratmoixniecdefaffetcetrsdaonsdi/nogramnodrtadlaiitliyest.hrToheugahniomtuahtle odbusreartivoantoiofntshfeor this assayare summarized in the following able:
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Animal Observations for Tosicity for Dose Raagefnding Assay |
TiDmoesiAnfgir LDeovseel (hour0s2 ) (mga/lkg) Wows
Observations
1000
1510
MRNaeolmreamianli#n97g61maalnedsFaepmpaelaree7d5h5u7n7c6h&eda9n7d08hyfpoouancdtidvee.ad
"168 ToeRemaining femaleappesred normal
23504100, Normal
11501000,,
i
402 22501400,
Toro RMemaAininTg male a6nd alol nfedmadleesadappear normal.
1000 Normal
- Tis MRemaaienivngemalloeawnmdddfeedmale appeared sormal
223500411000,, Normal Tw News
1510 RReemmaaiinniinngg mfeamlael#e 9sp7p7e4srfeodunndordemaadl.
=88.5 22051400, Normal
;
Soro Remaining male #9764 sppcared Fypoacive and bunibed
------vwiti h 2 rout ghhhaaiirh rccooaatt..a AAlll ffr eemmaalleesso sappppeesau rreedd nnoog rrmmaall..h
The mortality datafo hi assay ae summarized inthe following table:
CHV Study No. 17750-0455
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SummaryofMortalties for Dose Rangefinding |
.
Teme
Mie Female
T1-060506m4g/kg
on
os
21051100 mmgghse
335
o2s%
2540 meg
3
o3
3010 mg/kg
23
03
104 Conclusion
.
Based on these results, the maximum tolerated dose could not be determined.
11.0 DOSE SELECTION STUDIYI
i
111 DoseSelection
gDaovsaegelefvoerlstohef s1e0c1o0n,d1d5o20s,e 2s0le2c0tainodn s2t5u3d0y.mg/kg were administered by oral
112 Dosing Information
TThhee awneiimgahltsruansgde iofntthhee saneicmoanldsduosseedseilnetchteiosneacsosnadydwoesreerdaongseedfionndiJnuglyas2s4a,y1w9a9s6.
:
30.1-35.8 and 23.6-26.4 grams, for the males and females, respectively. Dosing
solutions were prepared just prior to dosing and were prepared by making &
253 mg/ml stock for the high dose (2530 mg/kg ). This was prepared by adding
deionized water (CHV, Lot # 20) up to a volume of 14.0 m! to 2.9 ml of T-656+,
rtheesu2l0ti2n0g,i1n5a2c0leaanrdc1ol0o1r0leesskseoludtioosne. leDviellus.tionsofthis stock were prepared for
.
Dosing was achieved using 10 ml/kg dosing volume. All animals were ight
`fwoeuenkdsianntdhetwfooldlaoywsionlgdtaabtlteh:e timeofdosing. An outlineofthe dosing scheme is
CHV Study No.: 17750-0455
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Dosing Scheme for Dose Selection Assay II
DTm65a6m4et 11502100 mmgg/hkgg 22052300 mmgg//kkgg
Male Female 3300s3 330033
(onteot-atlimoef 2o4nlayn)ibmaasliss was used inthisassay. All doses givenwere onan acute
113 Results and Interpretation
i
Asltludayn(itmharlese dwaeyrse)efoxamtionxiecdeafffecrtdsoasnidnlgoranmdortdaillityietsh.roTuhgheoauntitmhaeldoubrsaetrivoanotifotnhse for this assay are summariizntehde following table:
1
Animal Observations for Tosiity for Dose Rangefindiag Assay II
TiDmoesiAnfgter LDeovseel
Observations
O(hLours) _ (mg0/kg) ome
"115796
om
1520 Femal#e1417 founddead.
`
--2MU""3a2S9156l1I5e S2Al0l #NMoalmlnae#l01405Sfouf nd deoad un0 ddesd
5696e0064s4 AAAAllUll NNNNeooommwwaadl!a
000
:
"The morality data for thi assay are summarized inthe following table
:
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Summaryof Mortalities for Dose Rangefinding II
T-- 6568_TeaMim le eFemt ale
11502100 mmeegg
o3s
o3s
22503200 mmeeffkkgg
[5 03
[055
114 Conclusion
2Ba0s0e0dmgo/nktgh.ese result, the maximum tolerated dosewasestimated 2sabout
s
120 MICRONUCLEUS STUDY
i
121 Dose Selection
B1a9s9e0dmogn/krgesuwletrseftreosmtetdheindtohsies ssteuldeyc.tion study, dose levelsof498, 995, and
122 Mictonucleus Assay Dosing Information
.
C`coTynhctelraoolnp,ihmwoaaslpsshsuaosmleiuddbieilni(ztCehPde),mini(csCrtAeorSniule#cld6ee0ui5so5na-is1zs9ea-dy2;wwaeStrieegrmd(ao,LsoLe#odtto#1n9,2Ju6plHry0ep43a70r,3e)1d,9a9tt6h.CeHpoVs)itive
i i
dateniidcolnweiazasetdadvmvaiotnleiursmt(eeCroHefYd,1b0yLmooltr/ak#lg2.g0a)v,Tahwgeaeswaetaid8gm0hi.tn0irmsagtn/egkregeo.dfctTohhneceuasvnreiehmniactlllsey ucwosinethdroitlhn,ethteest
rmeiscpreoctniuvcelley.usaTshseaydwosaisng3s1o.lu0ti-o3ns7a.nfod7r t2h2e.4a-s2s8a.y3wgerraempsrfeoprartehed mbaylmeaskainndgfae.meles,
::
d1e9i9onmigz/emdlwasttoecrkCfHorVt,heLhoigt#h d2o0s)eu(p11909a0vmogl/ukmgeo).fT3h0i.s0wmalstp0re4.p9armeldobfyTa-d6d3i6n.g, resulting in.clea colorless solution. Dilutions ofthis stock were prepared for
hStiheegcho9n9ddo5asareonydfDt4oh9se8e emGsgrt/oukaprgi)cdlwoeas. es Tlaehlveseosle.asasnAiigmsnaeeldcsotnwodetrgheeroosuntpluodyyfuasaneniddmiwanaltsshed(doaesssesidagynwai2tt5ehdthe
replacement for any which died in the primary dose group.
CHV Study No: 17750-0455
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`hTaernveasntimtailmse (gfriovuep.malVeehsiacnlde fainvde pfoesmiatlievse)cownetrreolragnroduopmsl,yeaustshiagnniezdedto each dose/daopspreodxwiimtahtetlhye 2te4shaorutrisclaefwceerrdeoseiuntgh,anwiezreed ainpcplruodxeidmaitnetlhye2a4s,sa4y.8 aTnhde7a2nhiomuarlss aisftfeorudnodsiinngthfeorfeoxltlroawcitnigontaobftleh:e bone marrow. An outlineofthe dosing scheme
Dosing Scheme for Micronucleus Assay
PrimaryNDuomsbeeGrroofuApsnimalsSeAcsosnidganreyd Dose:
--J Treatmentr ~~ es MM2FFH Mm 4M8FFH M2Me F FH MGTrm MowFFp
T6364 498 mgkg
55 55 ss -
995 mg/kg
55 55 ss -
1990 mgrkg
55 55 55 10 10
Vehicle Control, deionized water, 10mlkg ~~ 5 5 - - .
-
Positive Control, Cyclophosphamide, 800 mg/kg 5 5 = . .
-
* rTehpelaacneiamnailmsaalsssiwghniecdhtdoitehdeisnetchoendparriymadroysdeogsreougprsouwperatetdhoesheidghanddosweerleeveoln.lyAulsleedxttora animals not used as replacements were euthanized at the completion ofthe trial.
dAostoitnagl woafs13e0igahntiwmeaelksswaansduosneed idanyt.his assay. The ageofthe animals at the time of
.
Volumes dosed were 10 mUkg and were based upon individual animal weights.
13.0 BONE MARROW HARVEST, SLIDE PREPARATIONANDANALYSIS
i
fAolltlhoeweadppbryopCriOateinhhaarlvaetsitontiamned,tpheenaentriamtailosn owfterheeetuhtohraanxi.zeTdhebyadChOerOin,g sionfhtaliastsioune,and
trpainpshfyesreresod ftoboctenhtrfiefmuogreatwuebersecroenmtaoivneidn.gT3h-eSmamlrrboowvinweassefrluumsh(eodnfertoumbethfeorbocancehand
aasnpiimarla)t.ionFaonldlpoowritnigoncesntorfitfhuegapteilolnetowpeerlelesptrheeadtiosnsusel,idtehseasnudperainratdarinetd.waTshreesmloivdeesdwbeyre.
f1i97x5e)d.inThmeetahiarn-odlr,ieadnsdlisdteasinweedreincMovaeyr-sGlirpupnewd.ald solution followed by Giemsa (Schmid,
:
CHV Study No.: 17750-0455
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`The slides were coded for analysis, and scored for micronuclei and the polychromatic
t
mueisrcyetrdhoronouccryleteceaotr(dePtdChEcee)sleltsodwantaoasr.meoOxcpnhrereostmsheaodtuisacasnepdreyrPtcCheErnSotscymptieecrr(aoNnniCumcEal)leacwetelelrdercatesicloo.srebdSa.tsaenTddhaoerndftrfheoeqrtumoestnacwlyeroef
PCES present in the scored optic field. The normal frequencyofmicronuclei in this
Crl:CD-1%(ICR) BR strain is about 0.0 - 0.4%.
.
N`TCheESfroebqsueernvcyeod finPtChEe sopvteircsfuiseNldCs EwShilweasscdoertienrgmtihneedfirbsyt
scoring the number 1000 erythrocytes,
of
PCEs
and
140 EVALUATION CRITERIA
-
14.1 General
The criteria for the identification of micronuclei were thoseof Schmid(1976).
arMiinncdgrwsoehnraupceelgdeeimneiwrcearrloelnyudcablreektilwyoecesctnaasi1in/oe2nd0aalanlndydogUcecnSuerrtraheledls.yizrMeooiucfnrdto,hneaulcPtlCheEoi.uhgahTdahlsehmauonrnipdtboaofrnddceorrsing ``mwoasrethtehamnicornoenumcilceraotneudclceeluls, wnoatstchoeumnitcerdoansucolneeusm;ictrhounsutchleeoactceadsPioCnEa,l nceoltltwwioth(or OmforPeC)EmsicarnodnuNclCeEi.s (Tbhlueissht-agirneiyngapnrdorceedd,urreesppeerctmiivtetleyd).the differentiation by color 142 Data Presentation and Interpretation
IDnadtiavairdeuasluamnmiamrailzdeadtabayresaelxsaondprdesoesnetegdr.oupTshfeorantahleysdiisffoefrtehnetsteidmaeptoainwtass.
performed using an analysisofvariance (Winer, 1971) on either untransformed
(when variances are homogeneous) and rank transformed (when variances are
:
ohfetvearroigaennceeowuas)s psriogpnoifritciaonntso(fpc<e0.l0l5s),wiatDhumnincreotntuctlteeistpe(rDuannniemtals., 1I9f5t5h,e`1a9n6a4l)yswiass
sn`ueesxgeadctoitmovbediencoatntetirromonil.n.eATwnhhaeilcychrsiedtsoerswieaergferoopudepesrt,feorirfmaminenydi,nsgweeparaerp.aotsseiligyvnieffoirrceeasnaptcolhynshdeairfivfneevrsoetnlttviefmdreoaamntdhe
dseatteicstticoanlolfy saigrneifpircaondtudcosieba-lrneedlastuetdisitniccraellaysesiignnmifiiccraonntupcolseiattievde rPeCsEpo,nsoer ftohreat
:
dleoasset level
rowenasesdpoocnsosneesinldoeevrrelae.dstnAaetgitasettsiitcvaaerl.tliycIlsneigetnihitafhtiecriancndatsuaec,neddthrneepfe rinoadliuacdisettbcaliteshiisiotnne iccrvaelr aalssyebsaaitsgneoidnfeiocndaonste.
scientific judgment.
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150 RESULTS AND INTERPRETATION
Adulraatniiomnoalfstwheeraessoabysefrorvetdoxiimcmseydmiaptteolmysafaenrd/doorsimonrgtalaintdiepse.riAoldlicaanlilymatlhsrionutghhoeuvtethhiecle
:
aapnpdropporsiitaitveehcaornvtersotltgimreosu.psAalplpteeastreadnncoermdaolsaefdtegrrdoouspisnagpapnedarreedmnaoirnemdalheiamlmtehdyiauntteillythe
dafotseer dgorsoiunpg.waAsppfroouxnidmdaetaed.lyA2l2l hootuhresr aanfiemradlossianpgp,eaorneedmnaolrema(l#1a6t0t5h)sftriommetahnedserceomnadianreyd
healthy until the appropriate harvest times
p`Tohleyctehsrtoamratticilce,eTry-t6h3r6o4c,ytiensdouvceerd tnhoesliegvneilfsicoabnsteirnvcerdeaisnetshienvmeihcircolenuccolnetartolesd in either sex
soirgantifaincyaontfitnhcerehaasrevsesitn tmiimcerso.nuTchleeaptoesditPiCvEescoinntrboolt,hCysecxleosphasoscpohmapmairdeed, tiondthuecevdehicle
:
`cmoanltersolasn,dwiftehmamleesa,nsraesnpedcstitvealyn. dTeahrrerodrdastoa sf3u.m8m6a%ri+ze0d.5b5y% daonsde3g.r5o8u%par+e0pr.e7s9e%nftoerdtihne
3 yl
dTaatbalear1e apnrdesienndtievdiidnuaTlaabnliem8a.l data are found in Table2s through 7. Historical control
160 CONCLUSION
`Tmhaermteoswt pmoatleyrcihalr,omTa-i65c6e4r,ytdhirdoncoytteisnudnudceeratshiegnciofnidciatnitoinnscorfetahsiesinasmsiacyroannudcliseicoinnsibdoenreed. negative in the mouse micronucleus assay.
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170 REFERENCES
Dacuonnnteorl,. C.J.W.A:m.ASmuuilst.ipAlsescoocm,pa5r0i:s1o0n9s6-p1r1oc2e1d,ur19e55o,r comparing several treatments with
D4u9n1n,e1t9t6,.C.W.: New tables for multiple comparisonswith a control. Biometrics, 20:482-
aHnedddSlael,a.mAo.,ne,HiMteF,.M., ThKieriknhdaurc,tiB.o,n Loafrmsiecnr,oKn.c,lMeaicaGsreagmoera,s.uT.r,ofNegweenlolt,oxGic.iWty.. Mutation Res, 123:61-118, 1983,
Schmid, W.: The micronucleus test. Mutation Res, 319-15, 1975
i:
eSMduc)th.amgiPedln,esWn:.u:mP,riTpnphc.ei3pml1ie-cs5r3ao,nndu1c9Ml7ee6t.uhsotdestffoorrTchyetiorgeDneetteicctiaonna,lyVsios.l.4Ch(Ae.miHcoalllaender,
:
`YWoirnke,r,SBe.Jc.:ondStEadtiitsitoinc,al1P9r7i1nciples in Experimental Design, McGraw-Hill, New
:
180 DEVIATIONS FROM THE SIGNED PROTOCOL
1. daInybsoatnhdanlostotfhrteheeddaoyssearfatnrgdeofsiinndgi.ngTshtiusdiheas,dannoimiamlpsawcetroenosbtsuedryviendtefgorritfyo.ur 2. aDnuiematloa#tsec1h5n7i6caalnodve1r6s2i6g.htT,hmioshreadthanno 1im0p0a0cetryotnhtrhocyitnetsegwreirtyeoantafhlyzsetdudyf.or 3. TOhnisJuhlayd3n1o,1i9m9p6a,ctfootnhtehdeifntiengirtiitvye osfttuhdye,stuhdeyh.umidity was recordaesd 75.1%
CHV Study No.: 17750-0455
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1"
00192
CORNINGHazleton 19.0 EXPERIMENT DATA TABLES
0
CHV Study No.: 17750-0455
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`CORNINGHazleton
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TABLE
MICRONUCLEUS DATA SUMMARY TABLE SPONSOR: 3M Corporation
TEST ARTICLE: T6564
A-S_SAY:17750
TREATMENT DOSE
HTAIRMVEEST MEA3%NMOIFCIR0O00NPUERCALNEIMAAPTLCEEDSsE. OR) MALES FEMALES TOTAL
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CHVStudy No.: 17750-0455 i :i
19 `
600194
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CORNINGHazleton
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TABLEZ
MICRONUCLEUSTEST -INDIVIDUAL ANIMAL DATA SPONSOR: 3M Corporation
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CHV Study No.: 17750-0455
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20
00195
`CORNING Hazleton
|
TALE
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CHVStudyNo. 17750-0455
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00196
CORNING Hazleton
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TABLE 4
MICRONUCLEUS TEST - INDIVIDUAL ANIMAL DATA
SPONSOR: 3M Caporsion
TEST ARTICLE: T6566
ASSAY NO: 17750
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CHV Study No.: 17750-0455
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00197
`CORNINGHazleton
TABLES
'MICRONUCLEUS TEST- INDIVIDUAL ANIMAL DATA
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SPONSOR: 3M Corporation
TEST ARTICLE: T-6564
ASSAY NO: 17750
TREATMENT --_--
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CHV Study No: 17750-0455
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23 00198
CORNING Hazleton
ames MICROTENST.UINDCIVILDUAELANUIMSAL DATA SPONMSCoOmprRsi:on TEST ARTICLE: as mpwprorm t?4------_pr--voi--tmh --p)ot_--ArTo--S --
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CHV Study No: 177500455
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2 00199
CORNING Hazleton
BLE MICRONUCLEUS TEST- INDIVIDUAL ANIMAL DATA SPONSOR: 3M Corporsion
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TEST ARTICLE: T-6564.
ASSAYe No: e 17750 TREATMENT
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CHV Study No.: 17750-0-455
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00200
`CORNINGHazleton
TABLES
MOUSE MICRONUCLEUS HISTORICAL CONTROL DATA 795 THROUGH 1255
TEDVaReLE vs
TuMNeEIsANCOFR1O0r00wUPaEERsPAOsLNEIsEPMAEALRT+Tt5RoE2rPaDCE||
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CHV Study No.: 17750-0455
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00201