Document q3EoJb9x79e3mEXvOM35w8xjx

Attachments to Letter to C. Auer dated May 4, 2000 AR )G- Ol 23 Perfluoroctane Sulfonate Studies Genotoxicity 1) Mutagenicity Evaluation of T-2014 CoC in the Ames Salmonella/Microsome Plate `FTeebstruFairnyal2R0e,po1r9t7,8.Litton Bionetics Project No. 20838, Protocol No. DMT-100, 2) Memorandum Report from S. R. Rohfing to A. N. Welter, dated March 31 1977, on Resultsofthe Ames Spot Test for Mutagenicity screening of various FCs, including Sample 12-583 which is FC-95, Notebook Reference 45867-24, 25. 3) Mutagenicity Test on T-6295 in an in vivo Mouse Micronucleus Assay, Final Report, Corning Hazleton , Inc. (CHV), CHI Study No. 17403-0455, May 23, 1996, and protocol and amended protocol 4) PFiFnOaSl,ReCpoovrat,ncCehrLaobmoorsatoomrailesA,beInrcr.a,tiCoonvsaninceHuStmuadny WNhoo.l2e07B8l4o-o0d-4L4y9m,ph3oMcytes with Reference No. T-6295.18, October 25, 1999. 5) Final Report, Unscheduled DNA Synthesis in Rat Liver Primary Cell Cultures with PFOS, Covance Laboratories, Inc., Covance Study No. 20784-0-447, 3M Reference No. T-6295.19, November 9, 1999, and protocol. 6) FMiuntaaltiRoenpoArsts,aSyalwmiotnhePllFaO-SE,scCheorviacnhciea cLaobloir/aMtaormimeasl,iIannc-.,MiCcorvoasnocmee SRteuvdeyrsNeo 20784-0-409, 3M Reference No. T-6295.17, November 5, 1999, and protocol. 7) Final Report, In Vitro Microbiological Mutagenicity Assays of 3M Company `LSCCo-m4p4o4u2n-d0s1T6-,2234M7 RCeofCerannecdeTN-o2.24T8-2C2o4C7,.1SR(IFCI-n9te9rnOaltdionFaolr,muSlRaI,PLro-j4e2c9t9Nwoh.ich is 510978%. of the diethanolamine salt of perfluorooctanesulfonate in water), September 5, 8) PPreorff.luNoircooolcataLnoeprSiulefnoon,at"eE,v"alpuraetpiaornedofatMutthaegreenqiuceisttyoSftJudoihens LD.evBeutleonpheodffo,nP(hP.DF.O.S.) 3M Corporate Toxicology, January, 2000. 9) Final Report - Bacterial Reverse Mutation Assay of t-1, Hita Research Laboratories, Chemical Biotesting Center, Study Code K01-1802, 3M Reference No. T-6667.1 (FC-98, Potassium Perfluoroethylcyclohexyl Sulfonate), September, 1996. 001794 MUTAGENICITY EVALUATION OF 1-2014 Cot AMES SAUOIRNELTTHEE/MICROSOME PLATE TEST FINAL REPORT SUBMITTED To: 33M4 CCOEMNPTAENRY SAINT PAUL, MINNESOTA 55101 [LiHon BIONETICS SUBMITTED BY: LI5T5T1O6N NBIIOCNOELTSIOCNS', LIANNCE. KENSINGTON, MARYLAND 20795 LBI PROJECT NO. 20838 FEBRUARY 1978 01795 I. SPONSOR: 3M Company IL MATERIAL A. Identification: T-2014 CoC B. Date Received: December 20, 1977 C. Physical Description: White powder IL. TYPE OF ASSAY: Ames Salmonella/Microsame Plate test IV. PROTOCOL NO.: DMT-100 Vv. RESULTS The results of this assay are presented fn Table 1. VI. INTERPRETATION OF RESULTS AND CONCLUSIONS Tofheintesvtitrcoommpiocurnodbiwaals easxsaamyisneedmpflooryimnugtagSeanlimconealcltaiviatnyd iSnacachasreormiyecses pirnedsiecnacteoroforglainviesrmsm.icroTshoemaclomepnozunydmewapsrteepasrtaetdidonisrefcrtolmyAraoncdloirn-itnheduced rats. Tthheerecowmapsouneditwhaesr qtueasntteidtaotvierveaorserqiueasliotafticvoenceenvtirdaetnicoensofsuscohmethat TchheenTiocwaldloys-eindiunceadll phcyasseisolowgaiscableloewffeactconatcentthreathiiognhestthatdosdeemolnevsetlr.ated atnhyistocxoimcpouefnfdecwta.s fTrhoem 0d.o1seurgantgoe50e0mpluogyepderfoprlatteh.e evaluation of Tohfearmeestulatbsoliocf tahcetivtaesttisoncsoynsdtucetmedweroen talhle nceogmaptoiuvned. inThtehetaebsstenwcieth TrAe-v1e0r0tanwtass orbespeeravteedd aatt 150000, u5g00doasnedle1v0e0l0 uing'sthebecianuitsiealofteisntc.reasTehde repeat test was negative. TohfearreastultTsivoefr tahcetivtaetsitsoncosnydstuecmtewderoen talhle nceogmaptoiuvned. inThtehetpersetsewnicteh ToAf-1i0n0crweaassedrepreeavteerdtanatts50o0b,ser1v0e0d0 aantd5020000ugugdodsoeselevpeelr pinlatteh,e bineictaiuasle test. The repeat test was negative. *Ibynfotrhenatsipoonnsowra,s sN.uIp.plwiaesd beyntetrheed.sponsor, If information was not indicated [rHy BIONETICS 1 01796 VI. INTERPRETATION OF RESULTS AND CONCLUSIONS (Continued) The test compound, T-2014 Coc did not demonstrate genetic activity in any of the assays conducted in this evaluation and was considered not mutagenic under these test conditions. i3 onBIONETICS> Subnitted by: Study Director > Fyussl 2.207% 0SecXtioJnagCahiineafth, Ph.D. Dame SDeupbanratnnmeanltianofGeGneenteitciscs and Cel Biology Reviewed by: _ D,ai: Bris tek 1=50) DDeipraercttaoernt of Genetics and Cel Biology at2e0/75 2 01797 ; 23Bo o2@g PROTOCOL 1. BURPOSE aThcetivpiutryposien oaf mtihcirsobsitauldyaswsaasytwoitehvalaunadtewitthheouttestthemaatdedriitailonfoorfgennamemtai-c Tian metabolic activation preparations. 2. MATERIALS A. Indicator Microorganisms AingdePsrcorciepdtuiroen oonf psatgreai1n0.verification is given in Standard Operat- Salmonella typhimurium TTAA--11553357 TTAA--%18538 Ta-100 Saccharomyces cerevisiae 04 8. Activation System 1. Reaction mixture Component. Final Concentration/ml GTlPuNco(sseo-d6i-upmhossaplhta)te Sodium phosphate (dibasic) KMeglCl, Homogenate $3 fraction 45 nunool} 100 mol 383 pmmooll 0.12.05 ml 2. 59 homogenate Aadu3l,t00m0alex rgat sulpiveerrnatianndtucewdasbyprAerpoacrleodr 1f2r5o4m fSivperagdauyes-Dapwrlieoyr 5t9o skialmlpleasccwoerrdeingcotdoed thbey plrootcenduumrbeerofanAdmeassseatyedal.for (m1i97l5l)i.bgyrammsethpordosteidnespcerribmeidlliinlitLeBIr aTnedchnrieclaaltivDeatPa44o8n/PRAaStO aLicvteirvit9y Product. [HBIONETICS 4 01799 2. MATERIALS (Continued) C. Positive Control Chemicals Tahcetivcahteimoincalasssauyssed afroer gpiovseintivine cTaobnlterol1s oifn tSheectnioonnacVt.ivatRieosnultasn.d 0. Solvent Eprietphaerre dsetioocnkizseodlutwiaotnesr oofrsodliimdetmhaytlesruilaflosx.ideAll(DMdSiOl)utiwoanss uosfedtestot mveantterieamlpslowyeerde amnaddeftisn ceofntcheenrtrdaetiioonnizeadrewarteecrordoerdDHiSnO.TabTlhee 1solo-f Section V. Results. 3. EXPERIMENTAL DESIGN A. Plate Test (Agar Incorporation)* Atoprprosxtirnaaitnelwyer1e0adcdeeldls tofrosnepaanratoevertneisgthttucbuelsturCeonotfaienaicnhg i2n.d0icmal= mFoolrtennonaacgtairvatsiuopnpletmeesnttse,d awtitlheasbtiot4indosaendleavetlrsacoef otfhe htiestsitdicnoen. pound poured were over atdhdeedsurtfoactehse ofconsteelnetcstivoef atghaer palpaptreosp.riatIne atcutbievsatiaonnd . ttehsets,appartoplreiaastte 4tudboesse lweivtehlsceolflst.he tJeusstt cphreimoircaltoweproeuraidndge,d atno aholmioqgueontatoef)rewaacstioanddmeidxttuoreea(c0h.5 omfl tchoentaaicntiinvgattihoen 9o,v0e0r0layx" gtulbievse,r w2himcihnivmearle atghaern mpilxaetde, aanndd tahlelowceodntetnotssoploiudriefdy.overThteheplsautrefsacweeroef irnocwuibnatgedonfoerac4h8 phlrataet. 37D4C yaenadstscoprleadtefsorwetrhee niunacbuebratoefd caotlon3i0esC Sshcoorneadc.tivaTthieonc)oncaenndtra3t7ioCns (ocftiavlalticohne)micfaalrs a3r-e5 gidvaeyns inanTdabltehen1 odfireScetcltyionacVt.ive Repsouslittsi.ve Pcohseimtiicvaelsanadndsotlhvoesnet ctohnattrolrsequuisriengmebtoat-h bolic activation were run with each assay. * pCreordtuacien cdleatsescetsabloef crheesmpiocnasless kunsoiwnng ttohebestnauntdaagrednsAmaensd acgaarrciniongceonrspodroatinoont mmeutthaogde.nicSaimne sduisapleknyslionniatsrsoasyasm,inebsutanndotceinrtatihne psluabtsetitasustaeyd. hydCrhaezmiinceaslsaorfe these classes should be screened in a suspension assay. UiAtonBIONETICS s 01800 3. EXPERIMENTAL DESIGN (Continued) 8. Recording and Presenting Data Tphreintneudmbefrosrmso.f coTlhoensieesrawondaetaachweprleateanwaelryzeedcouinnteadcoamnpdutreercorpdreodgraonm aanntds re(porortceodnveonrtaantpsrinftoorutD.4) Tpheer rpelsautletsfoarreeapcrhesienndtiecdataosrresvterrati-n evmipdleodyeads irneftehreenacsesayp.ointTsh.e poOstihteirverealndevasnotlvednattacoanrteroplrsovairdeedproo-n the computer printout. 4. EVALUATION CRITERIA Palasteet toefstsedlaetcaticvoensaigsatrofpladtiersectseerdeevderwtiatnht cpoopluolnayticoonusntsofobmtuatianntedceflrlosm sceulslpsendaered iinncuabatseedmiisnoltihde oovveerrllaayy. forBec2audasyes,thaendteastfecwhecmeilclaldiavnidsiotnhse onactcuurre.durAilntghotuhgeh tihnecsuebatfieoanturpeesrioodf, thteheastseasyt riesducseemitqhueanqtuiatnattiitvaetioinn otfatirveesulstuss,pentshieoyn ptreosvti:de certain advantages not contained in a quanti Tthoeacstmaloln nruempbleircatoifngcelDlNA,diwvhiisicohnsispeorfmtietnsmoproteensteinaslitimvuetagtehnasn nonreplicating ONA. `+ Tohveerlcaoymbipneerdnitisnccuobnasttiaonnt ofexptohseurceomopfountdheanidndtihceatocrellcsellisn tfhoer 2 days. A. Surviving Populations Pnluamtbeer toefstceplrloscesduurrevsividnog cnhoetmicpaelrmittreaetxmaecntt.quaAnttiltoawticoonncoefntrtah-e mteinotns polfattehse tiesst ecshseemnitciaall,lythethseurvsiavmiengaspoptuhlaattioonn otnhethenegtaretaitv-e ciosntruoslualpllyate.reduActedhibgyh csoonmceentfrraatcitoinosn,. thOeursurpvriovtioncgolponpourlmaatliloyn ehmipglhoeysst osfevetrhaelsedodsoessesrabnegiinngg soevleercte2dorto3 sThoogw csolnicgehnttrtaotxiioncsi,ty thaes determined by subjective criteria. B. Dose-Response Phenomena Tihmepodretamnotnstcrraittieornioonf idnosee-srtealbaltiesdhiinngcrmeuatsaegseniincimtuy.tantA cfoaucnttosr isthaatn might modify dose-response results for a mutagen would be the H LonBIONETICS 6 01801 4. EVALUATION CRITERIA (Continued) B. Dose-Response Phenomena siceilteyctiaorne orfeladtoesde)s. thaItf atrhee thoioghelsotw d(ousseualilsyfmaurtaTgoewnericitthyanaandtotxoxi-c cseolneccetnetdr.atioCno,nvenroseliyn,creiafsetshemlaoywebset odobsseerevmepdlooyveedr itshehidgohsley rcyatnog-e taonxdict,he tchoemptoeusntd wcihlelmicnaolt ampapyearkiltlo baenymumtuatgaenntisc.that are induced, C. Control Tests . ePxopseirtiivneentanadnd nceognastiisvte ofcodnitrreoclt-aacstsianygs muatreagecnosndfuocrtendonawcittihvateiaocnh aascstaiyvsatiaonnd amssuatyasg.ensNetghaattivereqcuoinrterolmsetcaobnosliisct boifottrhaenstfeosrtmactoimopnounidn psoonlevnetnst. in Tthhee onveegraltaiyveagacronttorgoeltheprlawteithfotrheeoatchherstersasienntigailvecsona rcoenfterroelnceaspsoaiyntfstocwohnidcuhcttehde ttoestdemdoantsatraarteecotmhpaatretd.he tTehsetpossyisttievmes are functional with known mutagens. D. Evaluation Criteria for Ames Assay . Bteesctauscehemtihcealpraorceedsuermeisquaunsteidtattoivee,valtuhaetecrittheerimautuasgeednitcoitdyetoefrmitnhee ponosiatihviestoerfifceacltsdaartea bianshee.renHtolystsduabtjaectsietvse aanrde aervealubaatseedd upsriinmgaritlhye following criteria: 1. Strains TA-1535, TA-1537, and TA-1538 cIhfemtihcealsotlhvaetntprcoodnutcreosl avaplouseitiisvewidtohsien trheesponnosremaloverrangteh,reea csoolnvceennttractointornosl wviatlhuethies cloonwseisdteriendcrteoasbee meuqtuaalgentioc.twicethe 2. Strains TA-98, TA-100, and D4 cIhfemtihcealsotlhvaetntprcoodnutcreosl avalpuoesitfisvewidtohsien trheesponnosremaloverrangteh,reea csoonlcveennttractoinotnrsol wivtahluethefohrigThAe-s1t00inacnrdeas2e-3eqtuiamles tothtewiscoaltvehnet cmuotnatgreonlicv.alueForforthsetsreainsstraTiAn-s9,8 tahned Dd4osei-srecsopnosnisdeereidnctroeasbee should start at approximately' the solvent control value. L[iHonBIONETICS 7 01302 4. EVALUATION CRITERIA (Continued) 0. Evaluation Criteria for Anes Assay 3. Pattern pBaerceanutsael TsAt-r1a5i3n5 (Ga-n4d6)TAa-n1d00beacraueseboTtAh-1d5e3r8ivaendd TfAr-o9m8 tahree sbaomteh dbeuriilvte-din frreodnuntdhaencysamien ptahreenmtiaclrobsitarlainass(aDy3.052)I,n gtehneerrealisthea ptawtotesrtnraiinss soofughat.set Irtesipsondalstoo atnhteicsiapmaetemduttahgaetn iafnda sguicvhena tsetsrtasi,n", iet.g.w,ilTlA-1g5e3n7e,rarlelsyponddos stoo ainmuatcatgievnatiinonnontaecsttisvat(iTohne csoinmvielrarse reosfpontsheispatrteelrantsioanrsehipnotisreqnuoitredexpfoerctealdi.).mutagWehnisl,e tdehceiysicoann. be used to enhance the reliability of an evaluation 4. Reproducibility cIafnnaotch"ebemicraelpropdruocdeudcesin aonreespoornsmeorein adadistiinognlael test that runs, the initial positive test data lose significance. Tfhaectoprrsecemdaiyngenctreirteirnitao aare finnoatl abesvoalluutaet,ionanddecoitshieorn.extHeonwueavteirn,g ptrheesseentcerditetroiaaiadre tahpospelieidndtiovidtuhaelsmajnoortitfyamoiflisairtuwaittihonsthiasndpraor- caetdiuorne.can Abse tmhoeredfaitraalbyaseestaibsliisnhcerde.ased, the criteria for evalu- E. Relationship between Mutagenicity and Carcinogenicity TIetstmusist nboet eampdheafsiinzietdivtehattestthefoArmcehsemSiaclmaolneclalrac/iMniocgreonsso.me IPtlaties rhaevceognbiezeend,`dheomwoenvsetrr,atetdhatbectowreernelatthievsee atnwdo feunndcptoiionntasl. reTlhaetiornesshuilptss osfhowcoamnpareaxttirveemeltyestgsoodonco3r0r0elacthieomnicablestwebeyn MrceCsaunlntsetofalm.icr(o1b9i7a5l) mutagenesis tests and in vivo rodent carcinogenesis assays. ArTe1poretvaalrueatiboanssedanodnlyinotnerptrheetadteimoonnstorfattihoen,daotra lparceks,enotfedmutinagetnhiisc activity. [LitHtonBIONETICS 8 01503 REFERENCES Acnaersc,inoBg.eNn.s, aMncdCanmnu,tagJe.nsanwditYhamtahseakiS,ilmE.one(l1l97a5/)m.ammMaeltihaond-snicfroorsodneetemcuttian:g genicity test. Mutation Res. 31, 347-363. Hceacracminn,ogeJn.s aCshomiitaE.g,ensVamainsatkhde, SaE.imoanndelfluas/sm,icrSoNs.one97t5es)t.: ADsestayecoftioo3fn00 chemicals. Proc. Nat. Acad. Sci. 77, 5135-5139. [rH=BIONETICSE s 01804 5. savas opeeaTING proceDups All data will be entered fn ink (no pencil). AThIroucghhangTehse ochrancgoer,recatnidonasn ienXoTeantrraiteisonwiflolr tbhee shaednegewitchta Ssionrglee LiTniene Shown on data meci AT calculations (weights, dilutions, dose calculations, etc.) will be AT data entries will be dated and fnittated. AmIaLnuaTla.boraTthoersye noapenraattsiownsilwiblel prbeesenwtrit1tenmacahutSatfnorasstaannddaerrdd2protocol fee Deviations from any established protocol will be described and Justi= GDaattaa bwoiollks bWeIT)stoDreedreivniewbeodundbyfcohrem s(pnoorteepbeoiokssseorsecbeirnodenrsa)d.s,These bound ating person Chemicals submitted for testing will have date of receipt and initials GLoeta miambevvrvseysfowrit)a1)berrefeecroerndcse. mutagens, selvent, or other materials ALnananiitensaeld AosrTudceharnsti,hmaartlesceeoaincphtss,aunisamnadwl Tfcdaennmtebiufp.irceSamrtaeiccoeensd wtsihTlothbeee strpneecorrideedd aanndd amaiinn: ASecoppeyraoafnatnhteiyfisntao)rerdepoirt.thpelus`araclh)ivarlawsydsactaenanntd Lsuiptpeomrtodcoucruimennctss wYiilo!l Current. curricula vitas and Job descriptions i11 be maintained on all S pSearlsBoonE nneelllaiTonTsvtorplaevimensdstyiwnpieltslh.ebsetOunrdoys.utaipnperlayntciheeccekresd sfoorretmhmed hiSsE, swirod,rerfsa, will be used in chemical evaluations. 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