Document pemvOdyrKZ879k1xGG9ZV14z6

MRARG- 2678 20 RAG - 4678 Duron 13970 `TRADE SECRET Study Title 124616: Hydrolyic Stability of H-24616as a FunctionofpH `TESTGUIDELINES: OECD Guideline 111 AUTHOR: Bogdan Szostek, Ph.D. STUDY COMPLETED ON: June 9, 2004 PERFORMING LABORATORY: EH.aIskdeullPLoanbtodreatNoermyofuorsHeaanldthCaonmdpEannvyironmental Sciences --- Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 LABORATORYPROJECTID: DuPont-13970 `WORKREQUEST NUMBER: 14644 SERVICE CODE NUMBER: 392 E Gompany Santzod.TTaSsarTsS NeoeTt Contain TSCA G81. -- HHaysdrsolley:te Stability ofH-24616 as a Functionof pt DuPont 13570 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT "LTahbiosrsattuodryywParsacctiocneduScttaenddiarndsc,omwphliicahncareewciotnhsiUs.tSe.ntEwPiAthTtSheCOAE(C40DCPFriRncpiaprlte7so92f)GGoooodd Laboratory Practice (as revised in 1997) published in ENV/MC/CHEM(98)17 and MAFF Japan Good Laboratory Practice Standards (59 NohSan Number 3850. The test substance was characterized by the sponsor prior to the initiationofthis study. Although the characterization was not performed under Good Laboratory Practice Standards, the: characterization was done by an ISO 9000 certified laboratory, and the accuracy of the data is considered sufficient for the purposes of this study. Applicant / Sponsor: EI. du Pont de Nemours and Company Wilmington, Delaware 19898 USA Susy Dissector: bo4 p STLo T `SBenoigodraRnesSezaosrtcehkC,hPeRmDi.st OJ f Du ate--2n 004 Applican/t Sponsor: "DuPont Representative Date -_-- CompanySanitized.Doss NotContTSaCAiCBnI. R228 ncasea VY QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 24616 Dates of Inspections: Conduct: 29-Jan-2004 Records, Reports: 29-30-Mar-2004; 2-Apr-2004 Dates Findings Reported to: Study Director: 29-Jan-2004; 7-Apr-2004 Management: 29-Jan-2004; 7-Apr-2004 -- Repredby: er E Ga4tet d? -TaBoe-zar compensins. S=okcrnTSAOL 2Hy4d6ro1l6ytc Stability of 24616 5a Functionofpit Dupont 13970 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluationof data obtained from this study. Approvedby-- : m = e 29=DTaudZ--oo Miosger -- met sitypts__BoppBopdS nSzeZ,PLD. Senor ReschChest _of-guw~2e 3 E Company Sanitzad. De oNotsContsain TSCA CBI. ARzzs 4Hy6dr1ol6yic Stability of H-24616 as a FunctionofpH. DuPont13970 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEcoMrrENT QUALITY ASSURANCE STATEMENT woos: CERTIFICATION rss LIST OF TABLES corre LIST OF FIGURES comms] STUDY INFORMATION sms8 STUDY PERSONNEL nnn SUMMARY mms0. INTRODUCTIONsss1 STUDY DESIGN crs:1 MATERIALS AND METHODS wcrc 1 -- 21. TeRsteSubss8a.n2cieT.BAdinuH-2a46:l16..........ororrrr nmmm----2 5. aPrHeIpaofrbufafertsoilutoionns em--m---------------------- 2Ir B5 FRR mSmmmnmmmemmmemmm--s--m------------------------ s--wpi 4. Equpihpo:ment... nepmm---- ------ -- -- I Bi MTo EFRrEgRuoawByrrmmwmeasgmmsmmmm------ n--m--r) 3F . AnaE olf eystssubsitansce. sm---------- a14 43.. EAiniaillotfymBcs2rTiBmA.sm..mmmnmmmmm------------ nmmsmm --------rh RESULTS AND DISCUSSION wocorrrsnrssmsssmssmsssssssnsne1n8 CONCLUSIONS c.ccossmsmmmsmmsmsssmsmsssmsssssssssmnsno3n0 RECORDS AND SAMPLE STORAGE wcvnssnsnmsmssmssmssmsmssss2n1 FIGURES rms35 `Company Sanitized. DI oNotCeontsain TSCA CBI. R228 EE HHy4d6ro1l6y:tic Stability ofH-24616 as a Functionofpil DuPont.13970 LI OF TSABLTES Page 1. A(n1a7l-yFteibc-a2l0r0e9s.u.l.ts for aqueous stabilityofH-24616, pH 1.2, 37C,Days 0 (12-Feb-20arn0d45)emit 2. Analytical results foraqueousstability ofH-24616, pH 4.0phthalatebuffer, S0C,Days 0 (5-FD30-052(000-4F)ED-2008)..rs 2% 3. AnRalEytOicDalIreBsulItsMfor aqueouissons sability of H-24616, pH 4.0citrate buffer, S0C,Days 0 (5-Feb-2004) nll 4. A(n0a3l-yFteibc-a2l00r4e)s.ultsforaqueoussa tabilir ty of-- H-24616, pH 7.0, 50C,Days 0 (29-Jan-2004) and. 5 mma 5. (AnaOly3ticFa rEesublts-fo2raq0ue0ou4s s)tab.ilictyorf Hn-2s46s16, pH 9.0o, 5s0C,Days 0i(n29-Jan-2004) and 5 swmennenlEl 6. Measuredconcentrationsof 8-2 TBAforpH 12, 37C,Days 0(12-Feb-2004)and (17-Feb-2009). .........28 7. Measured concentrations of-2 TBA (5-Fb-2004)and 5 (10-Feb-2004). for pH 4.0, C,pH . 4.0phthalate sr buffe--r--, --50C, Days 0 2 8. Measured concentrationsof82 TBA for pH 4.0, SC, pH4.0citratebuffer, S0C,Day0s (5-F3b00-5(120-F0eb-020048).).. 30 9. Measuredconcentrationsof 82 TBAfor pH 7.0, 50C,Days0 29-Jan-2004)and 5 (03-Feb-2009... 31 - 10. Measuredconcentrationsof8-2TBAforpH 9.0, SIC,Days 0 (29-Jan-2004)and (03-Feb-2003). 2 11. Dailytemperature readingsoftheshaking Water Bah.. nnn 33 12. pHmeasurforeDamy0eanndDtays5. sommmmsm-- I `CompanySanitized.DRos2s2N6ot ConTtSaCAiCBnI. HHy2d4r6o1l6y:tc Stabilityof24616 as FunctionofpH. DuPont.13970 LIST OF FIGURES Page 1. Eflxuaomripnlaete"dFacNtiMveRinsgpreecdtireanotfre1c0o5v0ermegd/iLnTflHuoEreixntatreadcatc(Bt)i,vainngraecdeiteonntitcrailliebreaxttiroanctst(aCn)dfaorrdD(aA)y,5, pH 40phthalate buffer, er----------------------------_ 2. uExoarmipnlteed"FacNtiMveRisnpgercetdriaenotfr2e10cmo/vli.enfrlTueHordFinaetxetdraacct(iv3e)i,nagnrdeadiceenttcaolniberaetxitornacstta(nCd)afrodr(DAa),y 5, PH 12buffer. en------------" 3 3. Eacxtaimvpeliengr"eFdNieVntRrescpoevceirreadiofnaTbHlEaenxktcroancttro(lBs)asmapmlpelfeorforDDaayy5,0p,hp1H.12.2bberur(A))an.dt.he.fluorinated 38 4. PEHxa4m.plceitr"aFteNbuMffRers(peAc)trnadofDthaeyf5,luporHin4a.t0edciatrcattievbeuifngfreedient re()c..o.v.ered in THF extractforDay0, 3 5. EpHxa7m.p0lbeuf"fFerN(MA)RansdpeDcatrya5o,ftpHhe7f.h0uobruincaete(d3a)ct.i.ve.ingredient recovered in THE extract for Day 0, 0 6. EPHxa9m.p0lbeuf"fFerN(MA)RnsdpeDcatrya5o,ftpHhe9f.l0uobruifnfaetre(d8a)ctive ingredient recovereidn THE extractfor Day 0, a 7. Reprealsibaetionn UtVaftor8:i2 TvBAe... 42 5. RA eprescatative chromatogramsof 102 g/L 8:2TBAcalibration standard and $20 pg/L D-82 TBA 2 - 9. R2e0prde5se2n0taptgi/vLeDc-h8r-o2mTatBoAgrianmtsemfaolrsDtaanyd5a,rdpH 4. citra.tebufferhydrolytiestabilitysample " 10.inRteeprmeaslensttaatnidvaerdc.hromatograms for Day5,pH 4.0 traebuffer blanksampleand 520 yg D-8:2 TBn A d `CompanySanitized. Doss NotContTSaCAiCBm nI. mm R228 2Hy4d6r1ol6y:tc Stability ofH-24616 a3 a Function of pt DuPont.13970 STUDY INFORMATION Substance Tested: [ 1 Synonyms/Codes: + H-24616 LI ] Haskell Number: 24616 Composition: [ ] [ 1 [ 1 t 1 Known Impurities in Total Solids: 1010 ppm Total Elemental lodine [1] <4160ppppmm Free Iodide lon [I] 1; (limit of detection = 10ppm) Note: --- 09.6444pWpemioghfttoptearlceinotdiTneelaotmterirbuBteldotdoidTeelisompreerseBntloidnide. 0 1 PhysicalCharacteristics: Opaque tan liquid Sponsor: EL. du Pontde Nemours and Company Wilmington, Delaware 19598 USA. Study Initiated/Completed: December 3, 2003/ (see report cover page) Experimental Start/Completion: December 22, 2003 / March2, 2004 -- `Company Saniizad. DRo2s2s 6Not Contain TSCA CBI. 4Hy6d1ro6l:ytc Stability of H-24616 as a Functionof pt STUDY PERSONNEL Study Director: Bogdan Szostek, Ph.D. Analytical Associate: Keith B. Prickett, B.S. Management: S. Mark Kennedy, Ph.D. Report Preparation: WandFa. Dinbokowitz Management: Kim D. Birkmeyer, M.S. DuPont.13970 5 ---_-- Company Sanitzed. Doss Not ContainTSCA CBI. Ars 2H4y6d1r6o:l Siabiliy ofH-24616 33a FunctionofpH Dupont13970 SUMMARY Hydrolytic stability of H-24616was tested in buffered aqueous solutions at pH 4.0, 7.0, 9.0 at 50C and pH 1.2.at 37C for five days. Concentrations of fluorinated active ingredient of HD-a2y4061a6ndweDraeym5earespulriecadtebysa"mpFlNesMfRorsppeHct1r.2o,sc4o.p0yphatnhdalpaetrec,e4nt0rceictorvateer,ie7.s0w,e9r.e0 cbuaflfceurlsa.teTdhfeor aavnedra8g6e p4e.rc0e%n,trreescpoevcetriiveelsyf.orTthhee aDvaeyra0gaenpderDcaenyt5r,epcoHve1r.i2esrfeoplritchateeDsaaymp0leasndweDraey150,4p:H3.4.60% phthalate buffer replicate samples were 93 + 2.9% and 82 + 6.9%, respectively. The average percent recoveries for the Day 0 and Day 5, pH 4.0 citrate buffer replicate samples were: P92H+7.30.r2e%plaincadte89sa+mp3l.e1s%,werersepe9ct7ive2l.y.0%Tahned 9a1ve+ra1g.e8p%e,rcreesnptecrteicvoevleyr.iesThfoeratvheerDagae yp0eracnedntDay 5, recoveries for the Day 0 and Day 5, pH 9.0 replicate samples were 98+ 4.2% and 92 + 0.81%, respectively. The fluorinated active ingredient of H-24616 was demonstrated to be hcryidtreorliyotniocfalDlyaysta0blaendatDpaHy95.0f,lupoHri7n.a0t,edanadctpivHe 4i.n0grceidtireantet bruefcfoevrerwiietshdtiifofe>rionng byyeanroumsoinrgetthhean a1t0ppHerc1e.n2t.andThpeHd4a.t0a-opbhtthaailnaetdefbourfhfyedrrsoilsytnioct cstoanbcilluistiyovef.fluTohreindaitfefedraecntcieovefirnegcroedvieerniteosffoHr-24616 fluorinated active ingredientbetween Day 0 and Day 5 samples waslargerthan 10 percent. The -- data indicates thaat significant portion of fluorinated active ingredient stays dissolved after additionofacetonitrile tothe samples that were exposed to test conditions in pH 1.2 and pH 4.0- phthalate buffer. Accurate quantitationofthe dissolved fraction offluorinated active ingredient `was not achievable for acetonitrile extract. Therefore, accurate mass balance of fluorinated atchteisveepinHgrdeiddiennottcionudlidcantoetabneyacchhaienvgeeds.oftThhee flFuoNriMnaRtesdpeaccttirvaeofitnhgreedaiceenttonmiattreirlieale.xtracts for `The measured concentration of 8-2 TBA did not indicate any hydrolytic degradationofthe cfolnucoreinntartaetdioancstiovfe 8i-n2grTedBiAentcamnatbeerieaxlptloai8n-e2dTbByAthfeorrepsiHdu4a.l08a-n2dTpBHA7p.r0ebsuefnfterisn. thTehteesotbserved substance (H-24616). For pH 1.2 and 9.0 an increaseofthe 8-2 TBA concentration beyond that athcactotuhnitseidnfcorreabsye rweosuildudalre8p-r2esTenBtAhypdrreosleynstision fth0e.t0e6stasnudbs0t.a0n3c%e wthaestoesbtsesruvbesdt.ancItewfaosr pesHti1m.a2taendd PH 9.0 buffers, respectively. RU Company Sanitized. Does Not Contain TSCA CBI. -- Azz 2Hy4d6ro1l6yic StabilityofH-24616 ss FunctionofpH. DuPont.13970 INTRODUCTION "The purpose of the study was to investigate the hydrolytic stability of H-24616 in pH 1.2, 4.0, 7.0, and 9.0 aqueous buffer solutions. "Thestudy was conducted according to the protocol: "Hydrolytic stability of H-24616 as a functionofpH", which was pattemed after the OECD Guideline 111.9 Additionally, the concentrationofthe 8-2 TelomeBr Alcohol (8-2 TBA)was monitored to investigateif 8-2 TBA is released from the test substance during the test. STUDY DESIGN A preliminary test was performed on the test substance at 50. 0.1C at pH 4.0, 7.0, 9.0 and at 37:0.1C for pH 1.2. If less than 10% test substance hydrolysis was observed after 5 days, the test substance was considered hydrolytically stable and no additional testing was performed. In addition to the test substance determination during the preliminary test, the samples were analyzed for 8-2 TBA. `The study design complies with the following test guidelines: OECD Guideline 111) with the exception that the OECD Guideline 111 requires that the amount of the test substance used is the smaller of 0.01 M orhalfthe saturation concentration. The test substance fluorinated active - ingredient [] ofH-24616) is essentially not soluble in water. Therefore, the study was conducted with excessofundissolved fluorinated active ingredient and the amountofthe test substance was suffictoisaetinsfty the sensitivity requirements of analytical method. Themolar concentration of fluorinated active ingredient was estimatedtobe 0.002 M (in 5. Calculations). MATERIALS AND METHODS A. Materials 1. TestSubstance Name: H2616 Composition: | ! Haskell number: ( 1 21616 `Thetestsubstance was polydispersity with the cfhoalrlaocwtienrgizreedsutltosd:etermine % fluorine, % solids, pH, Mn, Mw, and -_-- hh Company Sanitzed. DAoRs2s2N6ot Contain TSCA CBI. 2Hy4d6r1o6ly:ti Sabilty ofH-24616 as a Function of pt - 9% SFolluiodrsin(ew(ww)w): CLoo pi 6 MMaw: CCoo polydispersity ta 2. Residual 8:2 TBA in H-24616 Duron 13570 Residual 8-2 TBA content in the test substance (H-24616) was determined by LC/MS using the osfamHe-2a4na6l1y6ti(caalppmreotxhimoadtealsyde4s5crmieb)edweinreAnianltyrsoidsuocfed8t-o2gTlaBsAs viinalMse,twheoidgsh.edF,iv1e0 rmeLpliocfatTeHsFamples (tetrahydrofuran) was added, vials crimped, and vortexed for 10 minutes on a multtube vortexer. A 0.1 mL aliquot of dissolved sample was transferred to a glass LC vial and 0.9 mL acetonitrile and intemal standard (D-8-2 TBA) was added. Calibration standards were made in 10/90% THF/acetonitrle in the range from100to 1020 ng/mL 8-2 TBA. 3. Preparationof buffer solutions "The following buffer solutions were prepared as described in the Annex to OECD guideline 111. a pHLX: `The 0.2 Sigma) M potassium chloride (KCI) in 250 mLofwater. The 0.2 was prebpydaisrsolevidng M hydrochloric acid (HCI) 3.78 g ofKCI was prepared (purity 99.0%, by diluting 4.93 of hydrochloric acid (36.5-38%, Sigma) in 250 mL water. The pH 1.2 buffer solution was prepared by placing 125 mL of 0.2 M KCl and 161.3mLof a 0.2 M HCl solution into a 500-mL flask and bringing the flask to volume with water. The pHofthe buffer was adjusted to 1.2 with hydrochloric acid. bo pH4: P1h0t.h2a1lagtoefbpufoftears:s0i.u1mMhydsorlougteinonpohtfhpaoltaatess(ipuurmihtyyd9r9o+g%e,n Sphitghmaal)atienw5a0s0pmreLpoafrewdatbeyr.disTshoelvpinHg4.0 buffer solution was prepared by placing 2 mLof a 0.1 M sodium hydroxide solution and 250 mL Vooflau0m.e1 wMitphowtaatsesri.umThhyedproHgoefntphhethbaulfafteer swoalsutaidojnuisntteodato540.00-wmiLthflhaysdkraonchdlborriincgiacnigd.the flask to Citrate buffer: 0.1 M solutionofpotassium dihydrogencitratewas prepared by dissolving 11.5 g osfopluottiaosnswiausmpdriehpyadrreodgbenycpiltarcaiteng(p4u5rimtyL9o9+f%,0.1FlMukas)oidni5u0m0hymdLrooxfiwdaetesrol.utTihoneapnHd 425b0ufmfeLr ofa v0.o1luMmepowtiatshswiautmerd.ihTydhreopgeHnofcitthraetebusfofleurtiwoansinatdojuas5t0ed0t-omL 4f.0lwasikthan1dMbrsinogdiinugmthhyedfrloaxskitdeo. -_-- Company Sanitzed. DforsseNot Contain TSCA CBI aHsysdtr:ic Stability of H-24616 1s a Function ofpit - c pHT DuPont. 13970 p`Thhoesp0h.1atMe, smoolnuotiboansiofcp(oKtHazsPsOisu,m ppuhroistpyh9a9t.e5w%a,sSpirgempaa)reidn b5y00dimsLsoolfviwnagte6r..81gThoefppoHta7sbsuifufmer sthoelu0t.i1onMwapsotparsespiaurmedphboyspphlaactiensgol1u4t8imonLiontfoaa 05.010M-mLsofdliauskmahnyddrborxiindgeinsgoltuhteifolnaaskndto2v5o0lmumLeof with water, The pHofthe buffer was adjusted to 7.0 with hydrochloric acid. a pHY: `dTihseso0l.v1inMg 3b.o7r3icgaocifdK(CHI;B(pOusr)itsyo9lu9t.i0o%n,inSi0g.1maM) apnodta3s.s0i9ugmocfhlHo;riBdOe;(K(pCuIr)itwya9s9p.r5e%p,arSeidgmbay) in s5o0l0utmioLnoifn w0a.1teMr. KTChleapnHd 91.006.b5ufmfeLr osoflaut0i.o1nMwassopdrieupmarheyddrboyxipldaecsionlgu2ti5o0nminLtooaf5000.1-mML HflyaBsOks and bringing the flask Sodium hydroxide. to volume with water. The pHofthe buffer was adjusted t0 9.0 with pWuartiefricuastieodnfsoyrsbtuefmf.erTphreepawraatteironrewsaisstiovbittyaiinse>d1f8r.o2mmaeBgaamohsmteeeamd.NAANlOlpbuufrfeerDsiolaumtioonnds wwearteer csteelrliulliozseed parcieotratteo fuislteerb.yTfhiletebruifngfetrhrsooluugthioCnosrwneinrge sStteorrieldizaattrioonoFmiltteemrpseyrsatteumrse.with 0.22-m 4. Equipment - pWaHtMeerteBra:th: OPrreicoinsiMoondReelci2p5r0ocAal Shaking Water Bath, Model 50, Precision AAuuttoocmlaatviec:Pipettes: AReMseSaCrcOh MPorode1l003,0120300, 5000; Eppendorfr CBeanltrainfcuege: MSoertvtaelrLAeEg-e1n0d0RT VoGlratsesxrVi:als: M10ulmiLubboerosviolritceaxteer,SeVrWumRType Reaction vias (Supelco) with 20 mm Bari Sepia (3F0omiilnSiblecfoonree)us0e..1" tick (Supelco. The vials and septa were autoclaved at 121C for B. Methods 1. Preliminary test `3T7heCprfeolripmHina1r.2y.teTsht ewassampeersfaomrpmleedpornepHa-r2at4i6o1n6pratocSe0duCreataenadcshtoufdtyhdeespiHgn4.w0a,s7.f0o,l9l.o0weadndfoart aaucthooclfatvhede pglHassstevsitaelds.anAdpp3rmoxLiomfataeplpyro4p5rimagteofbutfhfeerHs-o2l4u6ti1o6nwwaass waeddiegdh.edTihnetovisailxstcweenre10c-rmiLmp c`waepreedpwriotchestsheedaflourmainnaluymsifsoialsctohveerDeadyp0arstaomfptlhese. seRpetamafianciinnggienisgihdte stahempvlieals. wEeirgehtworfatphpeedviwailtsh tdhaeysalatumthienuapmprfooiplr,isautbemteermpgeerdatiunret.he wEaitgehrt bviaatlhs, caonndtasihnaiknegnoantly1030mrLpmofinaptphreowpartieartebbautfhffeorrwievree -- prepared to serve as the blmankes.cFcouraofthem were Th usedaas the DYayC0blnanikcsaamnadtthue ostthaerrtfour CompanySanitized. DRo2s2s 8NotContain TSCA CBI. 4Hy6dr1o6ly:ic Stability of H24616 5 Functionofpt Dupont13970 wviearles cwornatpapienidnign3AmlLfooilfaanpdprpolparcieadteinbutfhfeewrawteerrebastphikteodbweitthhe8D-2ayTB5 Ablasntkosc.k sAodlduittiioonna(l4.l5y,psLixof s1e0p2t0a mfagc/iLng8i-n2siTdBeAt)h.e vTiahl.e vTiahlrseewoefretcherivmipalcsawpepreeduwsietdhatshethaelQumCisnaummplfoeisl cfoorve8r-e2dTpBarAtofthe banaatlhystiosgeotnheDrawyit0h. eTighhetoofthtehretthersetesvuibasltsawnecreeviwalrsa.ppTehdeisneasleurmveidnuamrofloeiolfanQdCplsaacmepdleinstfhoer water w8-e2reTpBrAoacneaslsyesdifsoorntheDafyluo5.rinFaotuerd oafcttihveeDiangyre0dioerntfooufrHo-f2t4h6e1D6aydet5evrimailnsatainodn.twTohbelaonthkevriaflosur of the 82 Day0 or Day 5vials, TBA determination. two blanks vials, and 8-2 TBA QC vials were processed for the. 2. pH measurement and temperature d`TehseigpnHatweadsfomretahseuHr-ed24o6n1D6aaynal5ysinist.heIvniaadlvserctoennttaliyn,ionngltyhepbHouffftehreanbduftfheerstewstassumbsetaasnucree,d on Dthaeyp0H, neloetctthreodpeHwaofssianmtprloedsucceodnttoaitnhienvgitahles taensdt sthuebsptaHncree.adiDnagyw5assatmapkelne.viTahlessweerveiaulsncwaeprpeed, "fTuhrethweartperrobcaetshsehdasfoarnHa-u2t4o6m1a6tiacnatleymspise.ratTuhree tceomntpreorlatbuuriletofin.thTehweatreeradbiantghsowfatshmeotneimtpoerraetdudraei.ly. control were checked and recorded daly. 3. Analysisoftest substance - wViearlesrdeecsaipgpneatdeadnfdorvoHr-t2e4x6ed16foarna1l0ysmiisnuwteerse. uAndcdaiptpieodn,of6amceLtoonfitarcielteontiottrhileeviwaalscaodndteadi,nivnigaltsest s"Tuhbestvaianlcsewseursepecnednetrdiifnugaedbuffofrerfisfotleuentimoinncuatuesseastt3he20f0luroprimn,atuendcaapctpievde,ianngdretdhieenltiqtuoidprpehciapsietawtae.s wraesmocvaepdpefdr,oamntdhethveianl.sonTiecnatmeidllifloirt3er0somfintuettersa.hydArpopfruorxainmea(teTlHyF)1 wmaLsoafdtdheedTtHo Fthesovliualt,iotnhewavisal panlaalcyesids.in aThgelabsslaLnCk svaiamlp,l0e.s1 wmeLreosfumbejtehcytle-ddtso-atlhceoshoalmewapsroacdeddeurdea,nwditshuobujtecpteHdmteoa'suFr-eNmeMnRt. T`Theen smtioncuktessooluftsioonniocfatHi-o2n4w6a1s6 rweaqsuimraeddetobcyomdipslseotlevliyngdi0s.s4o5lvgeotfheH-te2s4t6s1u6bstiannc1e0.mLCaloifbTrHatFi.on csatlainbdraartdisonfosrtatnhdeaHrd-s24r6a1ng6eadnaflryosmis2w0e0rteo m2a0d00e mbgy/aLpoprfofplruioartiendaitleudtiaocntoifvtehiengrsetodcike.ntoThfeH-24616. FLrienseharsrteogcrkessosliuotnoiofntahnedpceaalikbraarteiaovns.stsatnadnadradrsdwceornecepnrterpaatrieodn fwoarseuascehdintosteasntcaebolifsahnatlhyesciasl.ibration curves. - Company Sanitzed. Doss Not Contain TSCA Cal. ARs H2616: Hydrolyte Suability ofH24616asaFunctionofp Instrumentation and conditions: DuPont139n0 NMR instrument: Bruker AMX360 with a "F/'H dua probe. Acquisition Parameters "PTuilmsee DProomgariamn:Sizzeg: 16k NDIuDemlayob:fS1ec0a5nrsc: 128. DPuulmsmLyenSegatnh: 2psec IRnescteriuvmeernGtaFnr:equaeuntcoym:at3e3d8b8y3t1h4i5n6stMruHmzent Processing Parameters: SWiizneodfoRweFaulncStpieonc:truEmM: 16k Window Size 50 Hz Peak Used for Quantitation -CF, resonance a 32.5 ppm 4. Analysisof82 TBA `Samples designated for 8-2 TBA analysis were processed by injecting 3 mL methyltert-butyl wetehreer u(nMcTaBpEpe)dtbherfoourgehMthTeBviEalinsjeepcttuiomnutsoianvgoaidglaansys slyorsisnegseo.fN8e-i2tTheBrAD.ayTh0envoiralDsacyontasianmipnlges " winejreectuendcMapTpBedEawnedre0.v1omrtLeoxefdtfhoerM10TBmiEnuetxetsraocnt waamsulttriatnusbfeervroerdtetoxaer.glaSsusbsLeCquveinatll,y0,.9thmeLvials aacneatloynsiitsrifloera8d-d2edT,BAs.piked with intemal standard, crimped capped, and subjected to LC/MS "uTsheed 1aHs,th1eH,an2aHl,yt2icHa-lpesrtfalnudoarrdodoefca8n--21T-BoAl.(97T.h6e%,1DO,ak1wD,oo2dD,Pr2oDd,uc3t-s1,3CW-ehsetptCaodleucmabfilauo,rSoCd)ecwaansol ((1M0500)m(ga/bLbr)oevfitatheedaansalDy-t8i-ca2lTsBtaAn)dawradsanudsetdhaesinttheernianltesrtnaanldsatradndwaerrde.pSrteopcakresdoliuntmioentshanol and w1e0r/e90s%tMorTedBrEefraicgeetroantietdr.ileT.hTehcealciablriabtriaontisotnansdtaarnddsarwdesrweeprreepmaardeed ifnretshhefroarnegaechfrcoamlib1r0a0titoon in `1T0h0e0c0aluigbr/aLti8o-n2cTuBrvAe.s wAecroensctonatnrtacletveedluosfinignttehmearlatsitoanodfatrhdewpaesakusaerde:a f5o2r0iopngs/Lm/Dz-8m-o2niTtBoAre.d for 8-2 TBA and peak area for ions monitored for D-8-2 TBA and the concentrationsof 8-2 TBA. `Company Sanitzed. Doss Note Containe TSCA CBe I. i-- Ar228 HHy2d4r6o1l6yt:ic Stability ofH-24616 as a Function ofpH DuPont.13970 Instrumentation and conditions: HMPSLICnsItnrsutmreunmtent 2`M0o,deMlic2r79o5m,asWsaters LCoClPuamr:ameters: Luna 30 C18(2), 20mm x2mm. Mobile hase: AB--wmaetteharnol Grad"iTeinmte:(min) "A "s 01 3300 0i 26 00 110000 681 3300 00 CInojlecutminonTVemopleurmaetwre: ~~ 3200C4 Column Switch: 240d 6 min MToSniPzaatriaomnetmeordse:: Electrospray, negative ions CCaopniellvaorlytavgoel:tage: 2i5v17 - SDoeusroclevaTieomnpeTreamtpuerrea:ture: 3000cC Data Acquisition Function: 8D--28T.2BAT:BAS: SoIIfR4oR6f3,46572,35;208-6mmzi;n0-6 min 5. Calculations Flow 0(2m5Lnin) 002255 002255 02s `fTlhueorfionlaltoewdiancgticvaelciunlgarteidoinesntwe(rTeabulseesd1-t5o).detFeorrmeixnaemtphlee,noimfi[nal c]ooncfeHn-t2ra4t6i1o6nscoonftHa-i2ni4n6g16[ | fthleuonroinmaitneadlaccotnivceenitnrgarteidoineonftfwlauosrwienaitgehdedacitnitvoetihnegvrieadlieanntdis3: m[Lofbuffer was added to the via]l `3m3e9a0sumrge/dLcoonfcefnlutorraitniaotnedbyactthievenoinmgirneadliecnotn.ceTnthra%etiorne,ctoivmeersy 1is00ca%l.culated by dividing the `fTohleloewxsp:etctheed (4.5noumLionfal)10c2o0ncmegnt/rLat8i-o2nTofBA8-2spTikBeAreinprtehesesnptikse4d.5 psaLmxpl1e0s2w0ansgc/aulLc=ul4a5te9d0ansg o8:f28:T2BTA.BAThiinsthaemoMuTnBtEwaesxterxatcrtaicst:e4d5w9i0thng3/m3 LmLo=f1M5T3B0En.g/TmLh.e eTxhpeec%tedrencoomvienrayliscocnaclecnutlrataetdion by dividing the measured concentration by the nominal concentration, times 100%. ``Tmhoelemcoullaarrwceoingchetnt(rMatni)oonfofflufolruiorniantaetdedacatcitvieveinignrgerdeideinetn:t[can be estima]teWdhuesni[ng aveorfageH-24616 iisngurseeddie,nitt.reTpareksienngtsin[to account that 3 mLofbuffer is us1e6d.7t8his10woumlodleroepfrfelsueonrtitnhaetemdolacatrive: _ concentration: 6.78 10 mole/0.003 L = 0.0023 M. The expected conceniration of -2 TBA in --_-- Company Sanitzed. Doss Not Contain TSCA Cal. Ars HHysd6roll6ytc Stability of H-24616 ss FunctionofpH DuPont 13970 - the MTBE extract if 10% of the H-24616 hydrolyzed to form 8-2 TBA can be estimated in the tfhoelltoewstinsgubwsatya.ncTeecnonptearicnesn[tof 4|5flmuoerionfeHa-n2d4a6s1s6umriepnrgestehnattsal4l.5flmugo.rinTeaikipnrgesiennttoaascc8o-u2nTtBtAha,t the hydrolysisofthe 4.5 mgofthe test substance would release: [ 1 0.79 mg 8-2 TBA. This amount of 8-2 TBA would be contained in 3 mLs of MTBE extract. `Therefore, expected concentration of8-2 TBA would be: 0.79 mg/0.003 L= 263 mg/L. `The H-24616 contains residual 8-2 TBA. The expected, maximum concentration of 8-2 TBA derived from residual 8-2 TBA in the MTBE extract (3 mL), assuming complete extraction for a 45 mg sample of H-24616 is: 45 mg of H-24616 x (0.019%/100)/0.003 L= 2.85 mg/L (2850 ug/L). - `Company Sanitzed. Doss NotContainTSCA CBI. R226 HHyaddr6o1l6y:ic Stability ofH-24616 35a Function of pit DuPont 13970 RESULTS AND DISCUSSION `HT-a2b4le6s116-5anpdrepseernctenttherercesouvletrsiefsorombetaaisnuerdedfocroDnaceynt0raatnidonDsaoyf$flrueoprliincaatteedsaacmtpilveesinfgorrepdHien1t.2o,f4.0, s7.a0m,p9l.e0s, arreesp1ec0t4i2ve3ly..6%Thaneda8ve6ra+ge4p.e0%r,creenstpercetciovveelryi.esTfhoer tahveerDaagye 0pearncdenDtaryec5o,veprHies1.f2orretphleicate Dreasypec0tiavnedlyD.ayTh5e, pavHer4.0apghetphearlceantterbeucfofveerrireepslfiocrattehesaDmpalye0saanrdc 9D3ay+ ,2.p9H% a4.n0dc8i2tr+ate6.b9u%ff,er rtehpelDicaayte0saamnpdlDeasyar5e,9p2H+7.30.r2e%plaincdate89samp3l.e1s%a,rrees9p7ec:ti2v.el0y%. aTndhe91av+er1a.g8e%,perrecsepnetctrievceloyv.eriTehsefor 9av2e+ra0g.e8p1er%cernestpreecctiovveelryi.esTfhoer tdhieffDearyen0ceoanfdavDearyag5,epreHco9v.e0rrieepslibceattweeseanmptlheesDaaryc 598a:nd4.D2a%y a0nd saanmdppleHs9o.0f.thTehifsluionrdiincaatteedsatchtaitvethiengfrleudoireinntatweadsaclteisvsetihnagnre1d0ie%ntfoorfpHH-s244.6016ciitsrahtyedbruoflfyetri,caplHly7.0, stable at these pH (tz >one year). c`iTthreatheyd(rToalbylteic2satnabdilTiatbyleexp3)e.riTmwenotdfiofrfeprHen4t.b0ufwfaesrsdwoenreewiutshedtwasoidniiftfaelreenxtpbeurfifmeerns:tsphwtihtahlate and ipnhgtrheadliaetnetbiunfaferbuifnfdeircawtheednthsautbtjheectbeudffteorpcroomlpoonsgietdioenxpaofsfuecrtes(t5hedasyoslu)baitlictlyeovaftfelduotreimnpaetreadtuarcet.ive _ (c5o0mpCl)e.teSliympprleyc,iptihteataedtdhietifolnuoofriancaetteodniatcrtiilveetiongtrheedviieanlt.coTnhtaeianimnogutnhte otfestthseuabcsttiavneceinwgoreudlidenntot rdeectoevremriende iinf tthheeuTnHacFcoexutnrtaecdt wpoorutlidonboeft3h0e-5f0l%uo(riTnaabtleed2a)ctfiovretihnegprhetdhiaelnattweabsufpfrere.senItn ionrdtehre to afcleutoorniintartieldeaecxttirvaceti,ntghreedNieMntRinsptehcetarcuemtoonfittrhieleeexxttrraacctts wwaass catotlelmepctteedd.anAdcacuqruaatnetiqtuaatnitoinotaftitohneof atcheetfonliutorriilneataendda3ctmivLeoifngarebduifefnetr)inwtahsenaoctetpoonsitsriiblleeebxetcraacutse(atcheetocnailtirbirlaeteixotnrascttancdoanrdtsaionf6s mL. folfufolruionraitneadtaecdtaicvteiviengirnegdrieednietnitn. thTehaeceftlounoirtirnialteeedxatcratcitvecionuglrdednioetnbtewporuelpdarperdecuispiitnagtethiefTinHtFrodsutcoecdk btoettwheeeancettohneiNtrMilRe emxteraascutruesmienngtTsHdFonsetofcokr.TIHnForadnedratcoedtoentietrrmilieneextthreacstenmsaittriivxi,tya dciaflfiebrreantcieon asltalnodwaerddothfe 8d-e2riTvaBtAioninobfotthhe ssoelnvseinttivsiwtya-sdimfafedreenacendfamcetaosr utrhaetdwbays tahpeplNiMedRtomceotrhroedcst.foTrhtihse `stmaenadsaurrdesmmenatdoeffilnuToHrFi.natHeodwaecvtievre,itnhgirsepdireonctediunrteheisacceotnosniidterirleedetxotrgaicvtevosn.ltyhesecmail-ibqruaatniiotnative results. present Table 2 results indicate that in the acetonitrile extract for sDiagnyifSicsaanmtplpeosr.tioCnoomfptahreisflounoroifnattheedFactNivMe Ringsrpeedciternat is of Dflauyor5inTatHeFd aecxttirvaecti,nDgraeydi5enatceptroensietnrtilienetxhtreaaccte,taonnidtraiclaeliebxtrraatcitondisdtnanodtaurnddienrdgiocaatecshtehmaitctahlechange that would ingredient be for DviasyiblSesbaymplFesNiMs lRow(eFrigbuyre111).% (TThaeblaeve2r)atghearnetchoeverreycoofvterhyefofrluDoariyna0t.edHaocwteivveer, ttoakdirnagwinatocoanccclouusnitonthaebsoeumti-hqyduraonltyittiactisvteabnialtiutyreo(tfzr>esounletsyefaorr)aocfetotnhietrfillueoreixntartaecdtsa,ctitivies:difficult - ingredieanst the difference may be coming from the inaccuracyofthe results obtained for the EE Company Sanitzed. Doss Not Contain TSCA CBI. AR226 HyHHd2yr6d1or6lo:lSSuabbiillttyyooff2424661166 aasaaFFuunnccttiioonnosf ppiH DDuuPboonatei1s35e7n0o abcueftfoenri'tsriplHe efxotrratchtes.pHTh4e.0obbusfefrervse.d Tsohleubsiolliutbyiilsistyueisscsuaenwbaeslinnokteodbtsoerbvufefderfocrocmiptorastiet,iponH,4n.o0t the buffer (Table 3). "tThhaend1i0ffpeerrecnecneto.fHaovweervaeger,resciomvielrairelsy btoetpwHee4n.0t-hpehtDhaalyat5eabnudffDera,yth0essaomlpublielsitfyorispsHues1.w2eirsemore eacntciovuenitnegrreeddifeonrttwheaspHdet1.e2ctbeudffienr.theTaabcleteon1itirnidliecaetxetsratchtast, a significant amount of fluorinated but, forthe reasons described above for texhterpahctthwalaastenobtufpfoesrs,ibalcec.urTahteerqeufaonriei,tatthiisodnaotfatwhaesflnuootricnoantcelduascitvieveabionugtretdhieenhtydirnotlhyetiaccesttoanbiitlriitlyeof TthHeFfleuxotrriancatt,eDdaayct$ivaecietnognrietdriielneteaxttrpaHct1f.o2r. pHHow1e.v2ebruf,fecro,mpaanrdiasocnaloibfrtahteioNn MstRandsapercdtriandoifcDataeyd 5 thatthe fluorinated active ingredient present in the acetonitrile extract did not undergo a cspheecmtircaaolfcahabnlgaenkthsaatmwpolueladndbethveisDiablye 0byTH'FF NexMtrRact(FfiogrupreH2)1..2.FiFgiugruere3sp4r-e6sepnrtessetnhte NthMe R PcoHmp7a.r0i,saonnd opfHN9M.0Rbusfpfeecrts,rareosbpteacitnievdelfyo.r Da0y and Day 5 THF extracts for pH 4.0 citrate, "sTthuedyc.onBtaesnteodfornestihdeuraelsu8l-t2sTofBfAivienrHep-l2i4ca6t1e6sowfatshemeHa-s2u4r6e1d6,betfhoerecotnhteensttarotfroefstihdeuahlyd8r-o2lyTtiBcA in 8H--22T46B1A6 wfraosmctahlecutleasttesdutbostbaenc0e.0d1u9r:i0n.g0t0h0e3%ti.meoAfshsyudmrionlgyttihcatstthaebibluitfyfeerxpeexrtriamcetnsta,llthteheexrpeseicdtueadl ~ chyodnrcoelnytsriastoiofntohfe 8f-l2uoTriBnAateidn tachteitveestinsgyrsetdeimenwtoouflHd-b2e4621.865wmogu/lLd (msocset5lCikaellcyulraetsiuolnts)i.n thTeherelease ocfon8c-e2ntTrBaAt.ionIoffte8n-2peTrBceAntionfthHe-2te4s6t1s6yshtyedmrowloyuzleddbreel2e6as3inmggt/hLe (8s-e2eT5BCAa,lcutlhaeteioxnpse)c.ted `sTaambplleess6-f1or0pprHes1e.n2t, 4t.0hpehmtehaasluraetdec,on4.0cceinttrrataet,io7n.0so, 9f.08,-2reTspBecAtivfeolryD.ayTh0eamnedaDsaurye5d rceopnlciecnattreation f`sa8m-p2leTsBbAeyofonrdptHhe1l.e2ve(lTatbhlate c6a)ninbdeicaactceosutnhteedinfcorreabsyetohfe8r-e2siTduBaAl 8c-o2ncTeBntAraptrieosnenftorinDathye5test sthuebsetxapneccet.ed"Tchoenccoenncternattriaotnioofno8f-28T-2BTABoArimgienaastuinrgedfrfoormtrheesiDdauayl08-s2amTpBlAe.s iTshceomDpaayra5ble with ccoonncceennttrraattiioonnoofri8g-i2naTtiBngAfirsohmigthheerrbesyidaupaplro8x-i2mTaBteAl.y T1.h5emogb/sLermvoerdeitnhcraenatsheeoefx8p-e2ctTeBdA creopnrceesnetnrtastioonnlyinedsitciamtaestetdhehyhdyrdorloylsyissiosfofaptphreotxeistmastueblsyta0n.c0e6t%o (f1o.r5mm8-2gT//B2A6.L30Thmigs/iLnc*re1a0s0e%) of tcohnettreoslt ssaumbsptlaensc(eQpCre)sfeonrt Dinayth0e taenstdsDyastyem$.deTmhonesatcrcaetpetatbhleevarleicdoivteyroyftrheseul8t-s2foTrBtAhemqeuaalsiutryement (teTsatbslyes6t)e.mTdhoenmoteaesxucreeedd csoingcneifnitcraanttiloyntshoefe8x-p2ecTtBedAcfoonrcepnHt4ra.t0icointroafte8,-2pHTB4.A0 oprhitghianlaattei,ngpfHro7m.0 the the residual 8-2 TBA (Tables 7-9). hydrolysisofthe test substance. This The indicates recovery that there is no results for QC contribution of 8-2 samples arc also in TBA the from aincdciecpattaebltheerianncgreea(sTeabolfes8-72-9T).BAThceonmceeantsruarteidoncofnocreDntaryat5iosnamopfl$e-s2bTeByoAndfotrhpeHle9v.el0 t(hTaatbclaen1b0)e aapcpcroouxnitmeadtfeolryby0.8t5hemrge/sLidu8a-l28T-B2 ATBbAeypornedsetnhteicnontcheenttersattsiuobnsteaxnpclea.inaTbhlee ibnycrtehaesreeissidual - 8-2 TBA and is indicative of generation of 8-2 TBA from hydrolysisoffluorinated active CompanySanitzed. Doeets Not Coentaimn TSCA CBI. ------et AR2zs nHyadrsoely:ic Stability of124616 55a Functionofpif Dupont13970 - (i0n.g8r5edmiegnt/aLt 2p6H309.0m.g/TLh.i*s i1n0c0r%ea)soefrtehpreesteesnttssuabnsteasntciemaptreedsehnytdrionlythseisteosft aspysptreomx.imately 0.03% Figure 7 shows chromatograms a representative for the 8-2 TBA calibration curve obtained calibration standard, Day for 8-2 TBA. 5, pH 4.0 test Figures sample, 8-10 show and Day 0, PH 4.0 blank sample, respectively. `Table cases, 11 summarizes the water bath temperature recording for pH 1.2, 4.0, 7.0, and the water bath temperature was maintained at the specified level + 0.1C. 9.0. In all TonalbylepH12osfubmumfafreriszewsasremsuelatssuorfetdheonpHDamyea0,sunroetmtehnetpsHfoorfpsHamp1l2e,s4.c0o,nt7a.0i,nianngdt9h.e0.teIsntasduvbesrttaennctely., `wTahse mateathseursepedcipfHioedfDnoamyin0albulfefveerlswaintdh tDhaeyde5vrieaptliiocnatneotsaemxpcleeesdifnogr a+ll0o.f1.the investigated pHs CONCLUSIONS a"tTh5e0hyCdraonldytpicHst1a.b2ilaitt3yo7fCH-fo2r4f6i1v6e dwaayss.teTstheed filnubourfifnearteeddaacqtuievoeuisngsroelduiteinotnosfaHt-p2H446.106, 7w.a0,s9.0 dtienmo>nosnterayetaerd. toThbee hdyadtraoloybttiacianleldyfsotrabhlyedraotlpytHic9.s0t,abpilHit7yo.0f,tahned pflHuo4r.i0nactietdraatcetbiuvfefienrgwreidtihent of -- Hfo-r2f4l6u1or6inatatpeHd a1c.t2ivaendinpgrHed4i.e0n-tphbtehtawleateenbDuaffyer0sainsdnoDtacyon5clsuasmipvlee.sTwhaes dliafrfgeerretnhcaeonf1r0ecpoevrceernite.s `aTdhdeitdiaotnaofindaicceattoneisttrhialteastiogtnhiefsiacmapnltepsortthiatonwoefrfelueoxrpionsaetdedtoacttesitvecoinndgirteidoiennstisntpayHs dissolved 1.2 and after pinHgr4e.d0i-epnhttwhaalsatneobtuafcfheri.evaAbclceurfaotreacqeutaonntiittraitlieoenxtofrtachte. dTihsesroelfvoerde,fraaccctuiroanoteffmlausosribnaaltaendceacotfive efxlturoarcitnsatfeodr atchteisveepiHngsreddiidennottcionudlidcantoet abneyacchhiaenvgeeds. toTthhee "flFuoNriMnaRtesdpeaccttirvaoefitnhgreedaiceetnotnimtartielrei.al, `fTlhueormienaatseudraecdticvoencienngtrreadtiieonnt omaft8e-r2iaTlBtoA8d-i2dTnBotAinfdoircpatHe4a.n0yahnyddrpoHlyt7i.c0 dbuefgfreardsa.tiTohnoefotbhseerved scounbcsetnatnrcaeti(oHn-s24o6f186-)2.TFBorApcHan1b.2eaenxpdl9a.i0naend biynctrheeasreeosfidtuhael 88--22TTBBAA pcroensceennttrianttihoentbeestyond that wwhaiscehstciamnatbeedatchcaotutnhtiesdinfcorrebasyerwesoiudluadlr8e-p2reTseBnAt hpyrdersoelnytsiins othfe te0.s0t6 saunbds0ta.n0c3e%wtahse otebsstesruvbesdt.anItce for pH 1.2 and pH 9.0 buffers, respectively. - a `Company Sanitizad. Doss Not Contain TSCA CBI. R226 2Hy4d6ro1l6yic Stability of 24616 35a Functionofpit Dupont 13970 RECORDS AND SAMPLE STORAGE `NSepweacrikm,enDs(eliafwaaprpel,icoarblaet),IrroanwModautnat,aainnd Rtehceofridnasl Mraepnoargt ewimlelnb,e Wrieltamiinnegdtaotn,HaDseklealwlarLea.boratory, REFERENCES 1. OGrugiadneilsianteisofnorfoTresEtcionngoomfiCchCeomoipcearlast,iHoyndarnoldyDseivsealsoapmFeunnctt(ioOnECoDf)p.H,MOaEyC1D2,Gu19i8d1e.linOeECD No. 111. --_-- `Company Sanitizad. Doss Not ContainTSCA CBI. R226 2Hy4d6r1o6ly:ic Stabilityof H-24616 as a Function ofpH. DuPont13970 TABLES Company Sanitized. Domsms Not Contain TSCA CBI. R226 HHy2d4r6o1l6y:tc Stability ofH-24616 15 FunctionofpH Dupont13970 - Table 1: A(n1a2l-yFteibc-a2l00r4e)sualtnsdfor(1a7q-uFeeobu-s20s0t4a)b.ility of H-24616, pH 1.2, 37C, Days 0 NoamFi mCronocecmrsnto |||MegsF emrneesmeCoornneannattson| Lo th rr rr r rr [aTov mm 1 wm Te] [CeTol=T ww 1 ww 1 wm] [oz ols] ow} wa 1 we] [rrdols] oo 1 we 1 ww | ---- TT 1 |Er TT 1 [aTTT we Ton Te w [a1 s oe 1 s s [a we 7T s mo 1 s ) Pas me | t wowe s Tw l1 1 - [meeTw 1 Tecovered in he THF= exact == rescamopvleeroefdaicnettohneitacreitloeneitxrtirlaectexntortacstaved rerperpreesseennttss notoamlinraelcocvoenrcyenftoramtiToHnEofafnodraicnttoneidtraiclteivexetirnagcrtedient inth buffer `Company Sanitizad. DossENE otContainTSCA CBI. R226 wSarle yof 246160 Fin oft Duron 3970 Tabl2e: Analytical resultfor aqueousstabilityof H-24616, pH 4.0 phthalate buffer, 50C, Days 0 (5-Feb-2004) and 5 (10-Feb-2004). petits,| Sei, [oe ole HE =a o Co o 1e1 o 1 w wow 1 m 1 ]| Cooooloel wwee w ww w] ] I= -- E c-- o Co aw |e w woww e [w ww] ] MCoC oNE E o T we NwoT w [ww] - | era TE SH EE ET ---- 2 recovered in the acetonitrile extract *?rerepprreesseennttss ntootmailnraelcocvoenrcyefnrtroamtiToHnFoffalnudoraicentaotneidtraiclteivexetirnagcrtedieat in the buffer e compae nySumtns, SSasah ContinTEe AC pHog Soi of 2461 3 Fulani pun Table 3: Analytical results for aqueous stability of H-24616, pH 4.0 citrate buffer, 50C, Days 0 (5-Feb-2004) and 5 (10-Feb-2004). petra,| oii Co oro o r wewe1 1 w wo w 1 ] ] o CT RCo EE w ETw -- --] -- --1 [-- 1 Comoe || o oe w w ww ow] ] TeT-- w 1-- | - TRE = [mo= o = |] ? recovered in the acetonitrile extract ? * md sive the vial most likely leaked during the experiment Day 5, replicate 2 excludedfromcalculation ntti ls _-- PoS i ESiy rt1616 nore omen - Table: Analytical results for aqueous stability of H-24616, pH 7.0, 50C, Days 0 (29-Jan-2004) and 5 (03-Feb-2004). SEs | es, mWeiurstheutahefd 1wi2r1e 6| peas Fluorinated active | oR e F r NeCE e e r e w I S Sr O ] ] Peee em] EE e T E s T T B e o] s ] Te] - e= T i ] I:iS es AY 2Hy4d6r1ol6y:tc Stability of H-24616 s a FunctionofpH DuPont.13970 - Table 5: Analytical results for aqueous stability ofH-24616, pH 9.0, 50C, Days 0 (29-Jan-2004) and (03-Feb-2004). Noomgirena Coonrcemron| | MeiarreseesntCoonrcen2t4r0a1ti6on rr rT Tr fooTolv1 wm T1 w foototal wo ww 1% fooToll wwe 1 swe Tw oo oo 0m 10] ---- TT -- meme Tw [mmantber02 i-- n 1 [oo TST mo 1 owTw [ooIsla] woT--w T7% ] fooIsTol oo Tm 1751 [ooTsTo m0Tow Tw 1 - | Tepes nomial coneenaton ofE Muorm| iesd Scmiveiingreedietnt t ibn JheBoUFirosne]n 5 --_-- `Company Sanitzed. DRo2s2sN8otContainTSCA CBI. HHiysro1l6yic Stabilityof 246161 Functionofpi Dupont 13970 Rll - Table 6: 5Me(a1s7-uFreebd-2c0o0n4c)e.ntrations of 8-2 TBA for pH 1.2, 37C, Days 0 (12-Feb-2004) and Coemrntntegh)| Comematon saty rrr rT [a Tee Peel Lo freTol aw 7 eee Tm rrr 1 1 |somta|5 tvoiuTion rrr rT [efoto oe10 | w| [ra oTeal a 17 m0 Tw | [2loTeol ww Tm Tw | rrr rT TT hw [wm | FT someon | 00 | - rrrT T eel Tw T771 Fe = To Fe eT Fefee TT [1 [| teeTaw 1 [T svioien |T 20 ] rr TT [2lsleal woTw Tw | esleal moTw | we| [zfsfeal meTw Tw | -- rrrTr TT ew | w| CT sonia | 06] . `Compane y Sanie izad. e Da oesN--otCo-- ntain--TSCA--CBl.-------- 2Hy4d6r1ol6y:ic Stability ofH.24616 3s a Function ofpit Dupont13970 Co] [em mn - Table 7: Measured co 50C, Days 0 ncentrations of 8-2 TBA (5-Feb-2004) and (10- for Feb- pH 4.0, 2004). 50 C, pH 4 .0 phth alate buffer, Concentration G1)|_Concentration4a) [eo] wm [eo Tol10 17 [eo Tol a 17 [ooTole 1 1] rrr 1 TT ee om 171] 1 | I smtetboisinTa 11 rrr rT | we Tw [eo ToTeaTM me1 ww Tw | rrr 1 hee [| FT Sobviboisin [12] - rrrr 1 feo ls Tw 7 feo IsTel1 1 feo Isls me 177 foodstelTe TT 7 Se 1 [hme | mo 1 [1|smtsiboiion Tio 11 rr rT r T [eo seo moTi Tw | [eo sTeal m0Tw1o = | rr ewTw | CLTTsoT viuiboinn| 55] --- `Company Sanitized. Does Not ContainTSCACB ARzze HH2y6d1r6ol SabiltyofH-24616 3 3 Function ofpil. Dupon13970 lem] - Table 8: M50eaCs,uDraeydsc0on(c5e-nFterba-t2i0o0n4s)ofa8n-d25T(1B0A-Ffeobr-2p0H044)..0, 50C, pH 4.0 citrate buffer, Conraion wl)|_ ConcnatonGi) rr [ooPop Pe [ooToda] wm 17 [ooTol m0 17 Co ow 1 [heme Tow ET1sotoiboisin| 0 rrr rT [eo TooToo hoo 17 mo | ma_| [oo ToToal ww 1 ww Tw | [ooToTdeal ww Tw Tm | rr rT ET ew |ow | EEE - 1 1 [oo Ps pT [oo Psp m0 [ooIs 0 17] [oofsPel 1 a0 T7777 rrr rT T mew T 0 ETT 1 somtwipoiion | 50 1 rrr rT [wo Ta] [eo TsTeam mo Tw|o ws | rrr rT TT anew Tw | CL TT soiaaveioin[5] ------ Company S-- antzedm. Dmovee NotContainTe SCA GBI. s; Re "Table 9: Measured concentrationsof8-2 TBA for pH 7.0, 50C, Days 0 (29-Jan-2004) and [eeen[| rrr TT [ro [olv1 aw T7777 [ro Jol=[Tw 17 [oo [os1Taw 1777] [ro [oI 1 we 17] rrr rT [1Thee 0 17 es] 11 rr1TT [ro[ol ea TwTw Tw | PelleleLoe Le) frolol ca woTw Tw | 1 7 T TT aes [Tw | - Setwiooioin[06 | rrr rT [ooIspvw T [oeTs a TwT w 171 [ooTsT 5 TwT m 11 [oo [5 1Tw 1 rT7 He ess 1TT1 [re[STea TwoTw ww | [re[sTeeTmTwa ws | [re [sTee TmTm Tw | 1 TT TT ew | ow | TT TsuT swoeiin | 20 | 6Hy1dr6ol:ytc ability of H24616 3 Function ofpi. Dupont 13970 - Table 10: 5Me(a0s3-uFreebd-2c0o0n3c)e.ntrations of 8-2 TBA for pH 9.0, 50C, Days 0 (29-Jan-2004) and [oeIo ----T-- 1 m me 71 [[ooooTo o o s 0 a [oe Tolv 1 1 TT ehsee ra 1 rTrT [[ooooTooTleee mm meT Tew w | 1 wwoon]| [r ooJoleo Tm r wm --1 1 | - TT Seibeowioi[ n |ws || rr 1 [ooTs Tw foe Ts oo os ee ese rrr 71 FT IThE ee T50T 11 1TT [ooIsle [mo T7770 | wm | [oe Tea me Tw | ow [oe oTea meTw1n| TTT TTT eww | CT SonteiT boioin| 0 | -- Company Saniized. D raazNeo otCos ntinTSCA Cal. 2H6y1d6r:ol Sability ofH-214s aF6un1cti6onofpit DuPont.13970 = =[= [= - Table 11: Daily temperature readingsofthe shaking water bath. I) 1 [eo 1 eo 1vam | we| [a oreT m | wo | [e rw T | wo| o aTT rew | wo| [T oreT m | wo | TT o 0 T 1wren | wo | oT wramn| wo | [Tore |n wo | [T wreT wn| a0| [5 1 orem | wo| [TwToren[mo | 1 - [eo 1 mo oman [a0 | [m emmT a [a0| [m TTSma0 [mo | [o Towaw | wo | e v0 TT oran[wo | 0 wrean | wo | t= [o 0 T swan| [o omT a | mo] [0Tima [m0 | [o omaT n[so | e 50 T TT oan[wo] C 50 T 1 wvwam[wo] -_-- `CompanySantzed. DRo2s2sN8otContain TSCA CBI. -- Se Nyse 33 Fees gt - Table 12: pH measurements for Day 0 and Day 5. --_-- T - m a ] -- Ca o a eee e E-- S--T-- a -- C -- om]a ------ -- CC o T oa a 1 me " e ie] e et w - a a a -- 1 ---- --" -- ---- -- m w e ete w w I e T ---- e -- e -- e -- 1 e mee" T e ee e e T mereroT nlsed] Fe a 37 ? pH 4.0 phthalate buffer 2 * pH pH rt merrell esd iw 1 not measured for replicate samples; measured buffer pH was 3.99 4.0 citrate buffer _ pH ere not measured for ee replicate mp ered samples; measured cpt buffer pH vswas 66.2929 _-- Sm p Sm T 2Hy1d6wo1l6y:tic StabilityofH-24616 as FunctionofpH DuPont 13970 FIGURES `Company Sanitized. Doos NeoteContaie nTSCA e CBI. r---- R226 HHsy6d1r6ol Stability of H-246163s a Function ofpif Dukont 13970 - Figure 1: cEaxlaimbrpalteioFn stNanMdRardsp(eAc)t,rafloufor1i0n5a0temdga/cLtifvleuionrginraetdeideancttrievceovinegrreeddiinenTtHF extract (B), and acetonitrile extract (C) for Day 5, pH 4.0 phthalate buffer. --- `Company Sanitizad. DoeoseNotContainTSCA CBI. precy HHayslsllyeic Silty of H-24616 a 3 Funcom ofpi Duron13570 - Figure 2: Example F NMR spectra of 210 mg/L fluorinated active ingredient calibration standard (A), fluorinated active ingredient recovered in THF extract (B), and acetonitrile extract (C) for Day 5, pH 1.2 buffer. e i Ne g wn J ' CL i Ie -_-- Company Sanit. FDowsNot Contin TSCA Gal. - Figure3: Example "'F NMR spectraof a blank control sample for Day 5, pH 1.2 buffer (4) and the fluorinated active ingredient recovered in THF extract (B) sample for Day 0, pH 1.2 buffer (B). r i e ETT 5LL of ere Torrem nHeaesle Sltof 2461 5. Ecoofnp Durnin Figure 4: Example F NMR spectra of the fluorinated active ingredient recovered in THF extract for Day 0, pH 4.0 citrate buffer (A) and Day 5, pH 4.0 citrate buffer (B). g i Le ry e Ls S ---- _--m Company Sante. GSooot Conan TSGA GB, 2H4y6d1r6o:l StabilityofH24616 3 3 Functionofphi Dupont-13970 - Figure 5: TExHaFmpelxtera'cFt fNoMr DRaysp0e,ctprHa o7f.0thbeufffleuror(iAn)ataenddaDctaiyve5,inpgHre7d.i0enbtufrfeecrov(Be)r.ed in i L rp = eee oy. --_-- `Company Sanitzed. Boos Not Contain TSCA Cal. RRzzs HyHHy2ddsrr6oo1ll6y:tcSStbabiillityyooffHH-22d466\166asssaPuFnunccttiioonnooffppitt DuDpupeomncti.1s3s9r7o0 Figure 6: ETxHaFmpelxtera"ctF fNoMr DRasype0,ctprHa o9f.0thbeufffleuror(iAn)ataenddaDctaiyve5,inpgHre9d.i0enbtufrfeecrov(Be)r.ed in i bl -------------------------------- -- T `Company Sanit-- zad. Doest sfNot C-- ontain-- TSCA -- CB. ---- A228 HHsy6d1r6o:l Sability of 24as6aFu1nct6ion ofpit Figure 7: Representative calibration curve for 8-2 TBA. `orormeplaotuinodn name: 8-2TBA coefficient r = 0.999604, 2 = 0.999208 alibration Response curve: 1.02191 * type: intemal Std x+ 7.10268 (Re2f ), Area* (IS Conc. /15 Area) urve type: Linear, Origin: Exclude, Weighting: 1/x As trans: None. 10539. DuPont.13970 Response 0 2000 4000 6000 8000 ppb) 10000 Figure8: aRenpdre5s2e0ntpagt/iLveD-c8h-r2oTmBatAoginrtaemrsnaolfs1t0a2ndpagr/dL. 8-2 TBA calibration standard 021004515 Smooth(Mh,1x3) hoo * 8236118A 4204852925334 SIR of chann4e6l3s,E552-3 24960005 o 021004015 Smooth(Mn. 13) 100 * prey 1583.520784, 212219334307096 SIR of channelsm5i-n 13046174,050268 o 150 2.00 300 400 500 min eet `Company Sanitzed. RDo2e2s 8Not Contain TSCA Cal. 2H4y6d1r6ol Sability of H.24616 a a Function ofpit Dupont13970 - Figure 9: sRteapbrielisteyntsaatmipvleecahnrdom5a2t0ouggr/La,msD-f8o-r2DTaByA5,ipntHer4n.a0lcsittarnadtearbdu.ffer hydrolytic 021004639 Smooth(iin, 123) 100, % 8237580A 1677393574053 SIR of5 chann4e6l3s,E5s23685004005 o 215 021004039 Smooth(i. 13) 100. 15-03.526T8A, % 212248616742954 SIR of 5 channelm5is-n 1.2486876,4502088 o 00 200 500 400 5.00 min Figure 10: aRenpdre5s2e0nptagt/iLveD-c8h-r2oTmBatAoginrtaemrsnaflosrtDanadyar5,d.pH 4.0 citrate buffer blank sample 021004507 Smooth(vn 1:3) 100 205 458SIR of' cha4n6n3,eE5l52s-3 438 NI 6817e0003 " 234 249 oR 021o004507 Smooth(hn, 1:3) 101 % 15.3852878 21120418374.9458 SIR of5 channels EmSi-n 122416674,050268 o 700 200 300 " 150 500 min -_-- he `Company Sanitzad. DAosRssNot Contain TSCA Cal.