Document zzR2BvLgpD9dqDBQjorpoMjg
ARNG 0309
2-[N-ethyl-N-perfruoloalkyl(C=1~ 8)sulfonylanino]ethylacrylate
Gstudy number 2862)
T-t6322.5
Sample pl
Tx
nclegend;
fest
BML, Ine,
[wom] EGEIVE] 05259
QUALITY ASSURANCE CERTIFICATE
TitleofSy :eMtahytlaagcyniiatlyitnebsatcitnegroifal2rNe-eeste attpeirroaslsoaayslgiC1) ulfomylamin]
StudyNumber: 2 8 6 2
Thisstudywasconductedtncompliawnicteh * StandardstobeObservedbyMutageniTcesittinyg
Institutions *(Notification No.76, Ministry of Labour, Japan, September1, 1968)and * GLPStandards
aNpEpralviSeidonteohIendBAuasgtsereicaIylndCNshoet.mri2ic9saBolasfrTMteh(eNPohtMaiirfsmiactcarteyiuotonifNcoal.eA3rf9aftoifotnhBseePsTlsra,andiMeniagnnaidsntIdrnCydoouofsrHtdreiyanlaatthpiaoenn,Bd1u5wree1la5fx6,r9e,& hcaertthetrheaptorttheedmreetsuhlotsdrseaflectptohceertooedsasteadaccutrhateetleys,taredescribedrei inthe alreport, and Thechcumstancesofauditsexd tpectionsares follows.
Dato a
Lem
DtoeMtanoafRgeepmoernttInspection
Man 23,1991
Revie of SOPandprotocol
amg1091
Apr 20, 1901
Genera inspection
Amz, 1591
Ar.18, 1591
Reenvdicewofudofrietwrdetpaotrat
p18, 109
Am20,19m A, 19%
ReGvioewrotffntJnapeerneenpsoert ReuvirewiofinftEnnoirsneport
A2p8, 1r991 apm 19% SQaufatliytEyvAalsusatainonDUenpiaertment BML, Ie
<r Anna
Tite MagMaesrahiro Keramocht
va Goi] 8 13
005260
QUALITY ASSURANCE STATEMENT
TleofStudy :eMitgteicthyinsbtyiantgoelfseNy-vtshyltatptieofncslesoasByCot 8)sulfone] Say Neer 2.8.6 2
xTdhiacreupotrethrsanbsatoniotfetdeboyrQiugailniatryeAposrtsNaon.2P8e,rsworninteleanids Jsacponasnid,ervedefdo opnreAspeent 6m1e9%, partiallyamendedsinceMarch, 195 BM nc.
eet forif 8, 7
Postion: BMaLnagTere, Quality AsrnceUnk, SeyEvaluationDepartment (CompanyNam andTie
Name :
MasahiroKuramochi
ao
ex Sr
Signat)
005261
STATEMENT OF STUDY DIRECTOR
Title of Study : A mutagenicity testing of 2-[N-ethyl-N-perfruoloalkyl (C=1~8)sulfonylanino]ethylacrylate In bacterial reverse mutation assays
Study Nusber : 2862
This 1s to certify that the above study was conducted In compliance with
"Standards to be Observed by Mutagenicity Testing Institutions"
(Notification No.76, Ministry of Labour, Japan, September 1, 1988) and "GLP
Standards Applied to Industrial Chemicals" (Notification o.39 of the
Planning and Coordination Bureau, Environment Agency, 0.229 of the
Pharmaceutical Affairs Bureau, Ministry of Health and Welfare & No.85 of
the Basic Industries Bureau, Japan, November 18, 1988).
Ministry
of
International
Trade
and
Industry,
Date : April 8 994
Study Director, Mutagenesis Tests Division Position : BML, INC.
(Company Name and Title)
Name : Yoshihiro Oguna (Type)
Yfsodite 1 (Signaturs
005262
Study number : 2862
Title of Study : A mutagenicity testing of 2-[N-ethyl-N-perfruoloalkyl
sutatton sssays (C=1~8)sulfonylamino]ethylacrylate in bacterial reverse
PurTpooseassoefssthethetesetf:fect of the test substance in bactertal reverse mutation assays.
N"oS.tT7ah7ni,dsarsMditsnuidsytfrowyras ofNpeartLfaaogbroeumnrei,dcitiJynapaaTnc,ecsotrSsdeapntcueesmibwneigrth1M,tihc1er3o8og8ru)giadanenildsimnse""sGu(isNdeoettliiffnoiercstahtifooinrn TCoooxridciintaytiToenstiBnugrseaouf, CEhnevaiircaanlsse"nt(SAogteinfciyc,atiFoon. Yo3.0620o7f otfhethePhPalramnanceiuntgioaanld AIfnfdauisrtsriesBurBeuarue,au,MiMniinsitsrtyryofof HeIanlttehrnaatnidonaFlelTfraardee &and303Indoufstrtyh.e JaBpaasni.c Wanrdn 311, w1a9s67)c.onducted In compliance with "Standards to be Observed by MLaubtoaugre,nicJiaptayn, TSeespttiensgberIn1s,ti1t9u8t8i)onasn"d "-G(LYPotSitfaincdaatirodns ANpop.lTise,d tMoinIinsdtursytriaolf CEhnevaitreoanlmseTMnt (AFgoetnicfyi.ca0t.io2n29%0o.f39thoef PhtahermaPcleauntniicnagl aAnfdfaCirosordBiunraetaiu,on MiDnuriesstsr,y oIfnteHrenaalttihonaan]d TWrealdfearaend& IXn0d.u8s5troyf, tJhaepaBn,asiNcovIenadbuesrtr1i8e,s 1B9u8r6e)au, Ministry of
in
005263
Sponcer
Name + Sumitomo 3M Limited Address: 3-8-8 Ninamihashimoto, Sagamthara-shi, Kanagawa 229, Japan Testing facility
Nase BNL,INC. Address: 1361-1 Matoba, Kawagoe-shi, Saitama 350-11, Japan Date of test
Initiation : March 18, 1991 Completion : April 24, 1991
Persons in charge
Study Director
+ Yoshihiro Ogusa
Persons in charge of study : Shigen! Kimura, Youko Hasegawa
Name of the person who prepared the final report, and date of preparation
Yoshihiro Oguma
Title: Study Director Date : April 24, 1991
I certify that this study was conducted under the specified protocol.
Nunehiro Terasona Title: Administrator Date : April 24, 1991
2
005264
1. Sumary TAIRSeSvSe,rse1m9utatiaonnd TaAsIsSaSy7s aunsdinEgschSearlimcohnieallscolityWpPh2imuwroirudmwersetracionnsductAeLdOo,n w2it4-5ho[ uatrNemse-utlae tb,ot litchheaytcetl sitva-tsiuNobn(s- .tCa=p n1c~ee 8)dsriudlffnoorntyu lianmodiunl coe)oestia hgynll iafcikrcyaynltal terevewrittahnts andto bnoet cfoomupnadrefdn awniythsttrhaeinssolwvietnht ocronwtirtohlosut amnedtabdoolsel-edepesnctdievnattionI.ncrease wae ccotnhIdtyiltawicaorsnysl.caotnecluwdaesd thnaott 2-m[uNt-aegtehnyilc-N-tpoerfbraucotleorailakylu(nCd=e1r~8)tsheulfeoxnpyelraimmiennot)al
005265
a
2. Date of study
Initiation of the dose-finding test : March 28, 1991
Initiation of the main test
April 9, 1991
Completion of the main test
+ April 12, 1991
3. Test substance
(1) Test substance
1) Name(Another name) : 2-[N-ethyl-N-perf(rCu=1o~l8)osaullfkonyyll
aninojethylacrylate {Sample D-1}
2) BML-code
BML-1107
3) Lot No.
108
4) Purity
+ greater than 99 % wt/wt
5) Name and concentration of impurities
+ phenothyadine 60+ 20ppm
6) Structural forula : hydroquinonemonomethylether 170: 35pm
CaF nes 50:NaI CHH,; CH, 0-C0u~CH=CH,
n=8 (mainn=1c~om8ponent) : ca. 78 % n=1~7: ca. 21 % (total)
7) Molecular weight : 625
8) Appearance at room temperature
+ amber wax
9) Melting point + 27-42C
10) Bolling point + ca.150C (1nailg)
11) Vapor pressure: information not provided
12) Solubility
+ 011 soluble
13) Degree of solubility
Water
insoluble
Dimethylsulfoxide (DMSO) : insoluble
Acetone
+ over 50 %
14) Partition coefficient
+ information not provided
15) Stability
+ stable
The test substance was analysed and all data are retained by the client.
005266 "te
@) sotvent
NMaasneufacturer:: AWackeotonPeure Cheatcal Industries, Ltd.
PLuortitNyo.
:: Bgroeoatzeer than 99% (Special grade of JIS standard)
4. controts
(1) Negative control
Negative controls were treated with Acetone only. (2) Positive control compounds veTthoe. names and concentrations of these compounds are glven In the table
Strain
ms00s ST TA98
WP2 uvrd
without S9(ug/plate)
wKaze (0005)) AFI-R2191 ((10..01))
AF-2 (0.01)
with S9(ug/plate)
m BPo() 5.0)
BP B(a)P ((55..00))
208
(10.0)
AF-2 (s2Vt-oak(on2d-aFPruudrr,yelP)Cu-hr3ei-nt(tySc-agnlri;etartLoeo-rt2-ftNuhora.nylL)9Aa5JcIr%T)y0lZa;midSepecial grade of JIS a (SYooklousPuaraetdCeheaical; Lot Yo. DCIs3ss; Special grade of JIS
standard, Purity greater than 95 %)
ICR-191 acridine 211 2-Methoxy-6-chloro-9-[3-(2-chloroethyl)aninopropylamino)
4
2(-Paotlynsocainetnhcreasc,eInnec.; Lot No. 52300; Purity greater than 95 %)
(ako Pure Cheaical; Lot 0. KPQ0S2; Special grade of JIS
B(a)p Bsetnazndoa(rad),pyrPeunreity greater than 95 %)
(sWtaaknodaPrudr,e PCuhreimtiycaglr;eatLeort tNhoa.n A9W5K3%7)51; Special grade of JIS Co.S..odLutsd.iaLzaidteX(oY. aS)003wVaAs),disthseolvoethderincdoimpsotuinldlsedwewraeterdi(sHsiaktavrledPhfnarNaaScOy C(oWmapkooundPsuremutCahgeesniiccalto IenadcuhstrsitersainLiwde.rseloutsedNof.or ApVoEsGTiStSi,ve cEoOnWtZroSl)s.: TtehsetseUswienrge cMhiocsreonorgaacnciosrsdsi,n"g tthoe tMhienis"tNreyw oGfuiLdaeboBuoro,k JoafpanMut(a1g9e86n)i.city
I.
005267
5. Matertals
(1) Tester strains
1) Strains used 12:21.) Base-palr substitution type : S. typhimurium TALOD, TALS3S E.coli WP2 uorh Frameshift type : S.tuphimuriun TASS, TALS37
2) Supplier and date obtained S. typhimurium TAL00 + National Institute of Hygienic Sciences, Japan; April 15, 1982 S. typhimurium, other TA strains Dr. Ames, U.C. Berkeley, CA, U.S.A.; January 20, 1988 E.coli WP2 uorh Department of Molecular Oncology, Institute of Medical Science, University of Tokyo, Japan; November 24, 1987
3) Reason for cholce These strains are well established as sensitive to many classes of mutagens and are widely used. 4) Condition of storage The cell suspension was mixed with dimethylsulfoxide(spectrophotometric grade In a ratio of 0.07 to 0.8 voluse and stored at -80C.
(2) $9 Mix
1) 89
Name:
58
Supplier:
Kikkonan Co.
Lot No.:
RAA-248
Prepared on: January 11, 1991
Purchased on: January 25, 1991
Specles, Strain: Sprague-Dawley Rat
Sex:
Male
Age:
7 weeks
Welght:
199-246
Inducing substance:
Phenobarbi(tPaBl) and ,6-benzoflav(BoFn)e,
L.p. injection
Dose:
PB=30+60460+60 mg/kg (4 days); BF<80 me/ke(1 day)
-6- 005268
2) Cofactor Name: Supplier: Lot No.:
Cofactor Boehringer Nannhe{n Yamanouchi K.K. mm
3) Composition of S9 Mix (per lal)
$9 fraction
0.1 m
MgCle
8.0 umol
KCL
33.0 umol
6-6-P
5.0 umol
NADPH
4.0 umol
NADH
4.0 umol
Na-Phosphate buffer (pH 7.4)
100.0 umol
(3) Minlnun glucose agar plates
Name Supplier Lot No. Prepared on Purchased on Storage
: Minimal glucose agar plates M + Nisshin Flour Milling Co., Ltd. + BM020CG + March 1, 1991 : March 11, 1991: stored at roon temperature
6. Methods
(1) Preparation of the test substance
By reason of Information from sponsor, the test substance was
dissolved and tested In Acetone. The doubled(100mg/ml) andhalf(0.05m1) of
concentration this solution
of the substance was was added to reduced
the toxicity of Acetone. Its solution was stored In refrigerator just
prior to use.
(2) Dose selection The dose range was determined from the dose-finding tests using the
following seven dose levels: 1.2, 4.9, 20, 76, 313, 1250 and 5000 ug/plate.
In the dose-finding test, growth inhibition was not found In all strains with or without metabolic activation.
Accordingly, we selected 5000 ug/plate as the maximum dose for all strains tested with or without metabolic activation. So for all tester strains, we used five doses serfally 1: 2 were generally used.
005269 1-
(1s30)tTahT8te1eisotnocaferplyNrlusotpcrheoaldfseuenreteaocfBh(rpoorstrethirtnahYciou,n.b2avtSeih(roa0onkxioInldngm)s(ec1tu0hal0ona1ddt0)eatd)he'is-fn%eot)ro.vo81rahecucatlutluStruCere.dtubteo csohnetaisnaritnyg BsuUbFFsotreaRntc(eesD,tIs4aT)nwdiwta0hs.o1utBaLddmoeefdtaebaoGclohicsfarehaschttibuvabacettisocrnoi,Ratlal0xn.ei5dnaiglun0o.f0v5a0s.A1LMaddNoeafd-ptthoho.esphstaeatneet oCffoosntt0a.i5tnaui1bneg. o0fF.o0r50.at1e8stosNfa-twphihetohstpeshseatttaesbuoDblsUltFcaenrac(ec.toiTTv.ha4et)iaoinxwtau0sr.5e8s1wiadsoefdpr5o9tnocmuibxsaacciehndtreofnboder a2Si0uxrtfauaircnee,tnofaandtwheatthemerincbioanmttahenacttlsuScooTfsCe.casceh2aratluPbloeaftev.teorpTehaeigsaeerdr.slaasayndthaepgnoaurardewddaesdovvse6lrlotnhteense rtoo'vKes1ro1tlaindptilraytceoasltonvrieoerosem wtIeenrmcepuebrcaatotetuderedf..or 4_5Arthecenatce,STbCactaenrdialthefnrotvhten mtaabbebritioofn vsaeslAiicedhdeedckbey1d:1vu0asriantigon>hsJeutsetrteoappsrciaoofpralretmo(i0cu.rs6oe%s,coBwpaeecr.ieo-a0ga.r5, L0o.h5i%stNiadCiln)e tahnadt 0.w5e0r4e Btihoeti.n cfoolri tshteraSi.n.fypALhLimprliaatninsgtrvaeirnes,doannedi0n.5d8u%plitcraytpet.ophan solution for
7t(.etsIntCicroipatoetslrhiiasamt,iotofif`coeratvnha4tel,urasetopilrrovoenedpnurtco'idbuclcoein.btlrdeools)ien-rcveralesaatsdeeedt.ecIitnnecdrtehaeInsemaatsbceloreuarsoetfd ornoeevveerorftmaantrchese StehtahnodGrweas pnooltar,sedthea5 raensualitds inmoeuvladlubaetincgontshiedeGroesdt eposstitsi.ve. Statistics 5. Results and atscusston
vienTrIdnheueceptrhteeFepesavdtreoersdrteea-snrfutIolsnntdsisTnoargaberleteetshs2tih.snowantnrdiicntehTeGahbnalatelsnoft1e,tsht2es,
and Figs.l, 2. The
satlhveenttestconsturbosltsancaend
figures
diddosneo:t
decetpievnadteinotn.ncrease was not found In any strains vith of wiihout metaberi
The positive controls shoved an increase In the maber of revertants
cproFomrppeoarnrteyd.`tthoosetheressuolltvse,nt negative.
controls, indicating that this
fo ws concluded tat thls
study was performed
test substance vas
sveas/Ypolfagotrueonrdthwaite1naobvIembrettiSao1b9noluiwgcas/palcfatoituvenadtitwonint.ahnoyutstsretaatb.oliPcreaccttpilviaattieon anndthoeveprlat1e.s2
inTdhiecatsetderniolebatcetsetrstarpercfoonrtaocndtnaotnioonchthrtohueghtoeustthsiusbsstxapnecretaaennd.t. the 59 als
~~
005270
5. Deviation tronprotocol ste.
foDuhraivneg tron the
aphfrfeoetcotscetoduld.ytheperFieoldl,sbItIhLeerYe
voefrethneo
deantav,iraamnsdentthaolrefavcatsorsnocodnesviisdteiroend
10. Conclusion
m(utCFar1toin8ontshuealssoaarbyoysvleoumnrideneosrluelttthh,eyleiaxtcpiewyralsiaatecenotnaclluWcdaoesndditthniamotonns2-.-mu[tNa-geetnilpsl--fpnerfrbuaccltoesrliiooln 11. Storage of the records and sasples
bAtEehAelstldthioesrrpeeeodcnsodaIrlndosfortathnhecdeonastr1aci0mhn-piuylveeeaadslr gsapetrenoererairaoagdte,oefdotfhdBeHutLrhsLeipInoNrgnCes.ctoohrrfidosesrL1s11ta0undbdyyoea(srslasainssspatiufeeitdsce.erdbetlhroeewg)atrowsdtiisln.lg 12)) PRercootrodcselcaonndcemrneinndgetnthstest substances 345))) RTReeascwtorddsasutbasontantchee Activities of Guality Assurance Unit 7)) TDhreafinoafltrheepofritnal report
12. References
(1)
SBsNt.enAmefso,r Carcinogens,
FP.rtDoh.ce.LeNDeae,ttle.catnAidcoanWd.ES.cahn.dDurSCslthoa,ns:s1i0f.AincNaotI.ia0op,nropvpeo.df16B2Na-ac1tt8ae5rr,einaaslrcThaensdt
172
(2) FCJla.arscaMlictdCosag,nenn,sProNac.s.E.NWaaSttplaignegAnacsra:nd,. BJSa.cctieK.roibaoUlrshi,,Te7as2nt.derNBo..SN0.t.ra5Ai.mn6ess7:5.w5iD8eh3t,ect1i9o7Fn5actoofr
(3)
(4)
IMn.HE.sLc.heGrriecehniaacnodt,W.JN.otaMtuiroienl:ReMs.u.t.ageSna.Tepspt.id-nsg2,us1in9g7 Trp' Reversion DX. Moron and BX. Ames: Revised Methods for the Salsonells
Mutagenicity Test, Mutation Res., 113, pp.173-215, 1983
(5) U1J5sa6ip6nagneNsiecrMoionrigsatnriysaso,f LJaabpoaunr,IndiunstNreiwalGuSiadfeebtoyokanodf fMeuatlathgenAiscsiotcyiatTieosnt,s (8) CYh.emTiocjallsaM,utaTg.ensY,oshKioduad,ansahnad GT.o,Ka1l9a7,5 in Screening for Decection of
.
005271
Tabte 1 -
Sehtae
mionion me
Fraseesfnity me
!
ooese[80Eoonn]lF8 nnl#88cww8HTm]l Eom EFosEseN[EcRm]EBEAmlE B00E]Fw Fie)
CPPo EEEm]BEPwT HiCwlSiT w] YHiTn] Cesee[tom cn]800ml #icm] dion]
EY ema oe[or[we [or| oe] f[we eme T7AF-z oT waws*] ar-2|av-z [ier-isi-]
SEE umber or TM
fm
1s
BLE] oe[oo [ne[ae[oe] [MemeTwcaieel aaa =| 2a
Hin i oe
ae
ns
| sine|stair |
m
29
005272
danset
Cua/plate)
alas
oy
2
[ome 1areso[ wom[ares[Carer [rer] or[ome[vine]amaosm [ome[amr]
BEST COPY AVAILABLE
005273
Fig. 1 (Colonies/Plate) 200
= Dose-response
180
160
140
120
100
80
80
40
20
oy
0
313
625
1250
curve 2500
No.2862 (se =)
0TAL00 *TA1535 oWPZuvrA *TA98 +TALS37
5000( x g/plate
Fig. 2 (Colonies/Plate) 200 180 160 140 120 100
80 80
Dose-response
curve
No.2862 (Ss 9+)
TAL00 #TAL535 OWPZUVTA TASS +TA1537
40
20
ol 2 y . o. o. =
0
313
625
1250
2500
5000( x g/plate.
005274