Document VMyBkwyM3M30LdEoa9dg7Zno

,CARRS AR226_ 1069 5_5463 seer Gz0R000%0 [3 a5. Kor-aDuPnont M. Dominiak - U.S. EPA APD cries stuns pie P.O. Box 80023, BMP 23-1324 `Wilmington, DE 19880-0023 `OPPT Document Control Office EPA East, Room 6428 1201 Constitution Avenue, NW Washington, D. C. 20460 February 12, 2002 `To Whom It May Concern, mePleaehseelftdinodnieDnecclnoesmebgdearn 1u7p,d2a0t0e1d.cTophyeoCfBtIheclDauiPmofnotr ptrheesienntaftioonrsumbomaintpttaeigdetoso2tn1heaAngde6n6cyfsat the withdrawn. These pages contain no CBI and should be included in the public record. Text has been `adtodpaegeds 21 and 66 to clarifythattheproposedtimelinesare subjectto changeandharmonitzhee study material names with those used throughout the balanceofthe document. Otherwise, these pages do not differ in any other way from the documents that were provided on December 17, 2001. The non-CBI versionofthis document is intended to replace the previous version (AR226-1042) in the public record. Pleasecontact meifyouhaveany questionsregardingthis submission. 3 Best regards, lh > RoSbt.eTretcCh.noBluocgky,CPohnDsu.ltant FPahco:ne:0238092825121425435 Email: robbeuckr@utsa..ducpo.nt.com way Pa on oe id I Conky DuPont Product Stewardship Update United States Environmental Protection Rr Agency ` 17 December 2001 R. C. Buck, G. L. Kennedy, S. H. Korzeniowski, J. C. Stadler SED: Chemica Sluons Emerpise CompanySeize:DonsNotConta ! Discussion Outline + + WReocroknnPelcatnsto&21ChFeemibsDtirsyc,usRasdiioon-label + Toxicology -- Biopersistence -- Repeated Dose, Reproduction & Developmental Studies + E~xpSotsruucrteurCe o-nAncteicvittiyoRnel:atWihonasthiptshe data means ~ Human Exposure : Worker Data, Consumer + E~nvEinrvoinrmonemnetnatlalFEaxtpeos&urEeffects ~ Phys-iChcemaicall Properties ~ Environmental Fate ~ Environmental Effects CDoinucslsusiioonns Company Sani"tized SEL Chemical Slutons Enterprise Compan SaDn onaNz oCo:an 2 2 CBI Information has been redacted URE: ChemicalSolutionsEnterprise CompanySSaalnitzaad..Doos Not Contain 3 DuPont Fluorotelomer Product Groups: Intermediates, Surfactants, Polymers 1) Intermediates CReCF, (TFB) SalesProducts FC| C) (elomerA), 2)SurtaNcttwoarnnt-s.Pha"sMpohlateeculwesh"ose F(CF,CF),CH,CH,l ~ (TelomerB) | fan CBI Information has been redacted F(CF,CF),CH,CH,OH (TclomerBA) [I F(CF,CF.),CH,CH,0C(O)C(R)-CHy 3)PolPp ymers ++ EAsmteirde + UUrreeathane Zonyl TTM cy: Zony1 TAN aon AIRE ChemicaSoluionsEmrpise Company SeiDzonNetCdon.an ` 3 Synthetic Strategies for Radiolabeled Fluorotelomers F_F CoF i "OH F_F | CF SN November 2001 DCSE R&D PRYChemicalSoluions Enterprise CompanySnkiDoezs NoetCodnt.a : General Synthetic Strategy oF RF CF --> CFE2o, -- CBFE 7 NN ! RF rfOH + T~FEprnacotticaalvasiylnathbelseisasnostoduermconesotrfartaedd;ioSlHabEelissues + Must use readily available sources of "C ~ eg. CO, (ex. BaCOy), NaCN, etc. ~ ample literature precedent for conversionof C=O into CF, ~ typical reagents: Et;NSF; (DAST); (MeOCH,CH,),NSF, (DeoxoFluor?) APH! Chemical Solutions Enterprise CompanySaDa oasNd otCo: ntain " # Radio-label Synthetic Routes + Multiple (5+) Deoxyfluorination routes explored using different starting synthons CBI Information has been redacted AEChemicalSluions Emerprise Company SenDowszNotaCo:nn , Successful Synthetic Route GBI Information has been redacted + Synthetic Route provides access o al the key Fluorotelomer Intermediates `Telomer A, Telomer B and Telomer BA PRD ChemicalSluonsEneprise CompanySaDno oztCo.nan - . Pr wardship Analysi: Toxicity T[Trs How & How much? Bioavailabilly Ie Does it do Cant What? wi Metabolism? itgo persist? Risk = f (Exposure, Hazard) WP: Chemical Soluons Enierpise CompanySanz.Boe NotContain 5 Toxicity Studies AcuteToxicity + Oral, Inhalation + Eye, Skin Irritation . Skin Sensitization Rep Dose e Toa xict ity Oral, Dermal Intalation (ABL) Basic evaluation set SaonetieToxiolty Expandedevaluation Developmental Toxicity Reproductive Toxicity Pharmacokinetics GD: Chemical Solutions Emerprise Company SantDoeszNoat Cdont:ain 0 6 Summary : In Vivo Biopersistence Screening of FluoroOrganic Chemicals in Male Rats + Purpose : To compare bio-uptake and bio-clearance in rat blood fora series of fluorotelomer intermediate, surfactant and polymeric | products including PFOS as a positive control. + Study: 10 consecutive days dosing via oral gavage, 84 day recovery period with analysisoftotal Blood, Live&r Fat fluorine on selected days (3 during dosing, 4 during recovery). + Analysis: Use fluorine data to compare internal exposure of fluoroorganic materials on a dose normalized or pmolar basis. (CBI Information has been redacted OL Chom Sluons Enerrise C5"Se othkn Conin u CBI Information has been redacted SB:hoSlm uionsi Emrpe rise CompanySaiz:DoaaNot Conan 5 ? CBI Information has been redacted GI:ChemicaSouons Enerpise CompanySantzad:Does otContain " CBI Information has been redacted om mr TE .| " CBI Information has been redacted WLChemicalSluons Enerprise ConCompanyS`Suanintiized.. DoowesNotContairn Biopersistence Studies -- Key Learnings Telomer-based materials do not act like PFOS in the blood or liver ~ Blood total fluorine AUCs much lower than PFOS ~ Liver total fluorine lower than PFOS CBI Information has been redacted AB:ChemicalStunsEmerprise Company SanDaszNotnCo,an 16 a Repeated-Dose Study Plans 90 Day Subchronic Study Determine systemic effects from repeated oral gavage exposure One-Generation Reproduction Stud Determine effects on parental capability to conceive, bear offspring and evaluate effects on offspring during pregnancy, early feeding and maturation to adulthood Developmental Toxicity Stud Determine effects on fetal development (1.e. growth, maturation, abnormalities) HER Chemical Solutions Enterprise CompanySanizo.DosNo Cota uw 90 Day Repeated Oral Dosing & One-Generation Reproduction Study DoseLevels three levels + control ExperimentalAnimal: ~~ Male & Female CD Rats Study Evaluations : 9R0Deaypeate Dosde : + appearance, behavior, weight, blood, organs and tissues, B-oxidation + U.S. EPA Health Effects Test Guideline : OPPTS 870.3100 (1998) Reproduction : + Adult In life : body wt., clinical signs, limited histopathology, female reproductive cycle time, sperm assessment, reproductive organs, mating, fertility; Pups: physical development and maturation to adulthood, reproductive organs. SI: ChemicalSolutions Enterprise CompanySanDoee s NotdCon. tain " 0 90-day & One-Generation Reproduction Study Protocol = 1 i Bi Protest' 3 rossoRE]ee Toxicity punsli wn [RIT wom ] Recovery 90-day Dosing Period sosyoosngrosa i 1 & ooumynd Reeprodusctive N jo G1 A2Ds2 Pwra ee hes, -- sy econ 25 dca Totoro Bloc CC ss 535% 5 & 23EEz i: oz } i A CrisSlt rete `CompanySanz:Dos etConan " Developmental Study DoseLevels : Three Doses + Control ExperimentalAnimal: ~~ Male & Female CD Rats U.S. EPA Test Guidelines : 870.3700; OECD Sect. 4, No. 414 Study Evaluations Determine effects on fetal development (Le. growth, maturation, abnormalities) Maternal:clinical signs, body weight, gross pathology Pup: sex, body weight, external, skeletal and visceral examinations ERD:CheSlmuioinscEntearprlise ComporySniDioezeotCdor:n " " DuPont Toxicology Studies Timeline* [200072001T2002 _] [Test Material Work 1304011020'30/40/1G201304G4 [Telomer Urethane [TTTTT1 Rl -- rrr [Telomer Alcohol I (Intermediate [90DayOralRepeatDose+1GenRepro(Rat)| | | [DevSetuylRanogefpindm er ent|a|lWRTTT 17 [GeneticTToxiriyE:iTnVivoCr-- omAb -- ||| L1 TT [Telomer [s00aRa--ngeFinT anTgMRL LTTT] [Ethoxylate [90DayOralRepeatDose.1GenAsproFwy|| || 11 [DevSeey Rlanco etwp oe menTtTaTlML T7171 [Developments | |} J [Telomer [RangeFraTnTgML LTT] [Phosphate [90 Day OralChronicRepeatDose (Rat) |Lo -- Ll] oor esoascion Sed a mm TolomerAcrylote [Rangefmorg | TTTTTT 17 Polymer [Developme|n [| a[ iS |way [30DayOralRepeatDose1GenReprofw|||| II"T"T7[7| [[PSrceamcmaartdoena Ths sa proposed timeline and subject 1 change. 2 WARYChemicalSolutions Enterprise `CompanySanlized.DoesNotContain Telomer BA Synthesis Chemistry CF,=CF, (TFE) F(CF,CF,),l (Telomer A) F(CF,CF,),CH,CH,l (TelomerB) F(CF,CF,),CH,CH,0H Telomer BA Straight Chain Alkyl 0: ChemicalSoluons Enterprise CompanySaDn otaNd otCo.nan 12 Actual Telomer BA Study Material Composition =] af] -- sf _ wT j 157 w/] _ - am / o os El F(CF,CF,),CH,CH;OH Chain co Length n= cm Number BI Information has been redacted ERD:ChemicalSolutionsEmrprise Company Sanaa Does Not Canal n Telomer BA : Repeated-Dose Toxicology Information F(CF,CF,),CH,CH,0H n=3-6 + Repeated Dose Toxicity : NOEL 25 mg/kg/day Reproductive Toxicity: NOEL 25 mg/kg/day + Developmental Toxicity: NOEL 200 mg/kg/day + Genetic Toxicity : Negative AMES, Chrom Ab TV Cmts CPS En * 1 Telomer BA : 90 Day Study Results StudyConclusion: NOEL = 25 mg/kg/day CBI Information has been redacted aChemica SoltisEmrprise `CompanySanitaizaadd.DonssNotContain = One-Generation Reproduction Study : F1 Survival Indices +7 SF a 7 s & [=m i =trative ot Coe" mGoasteaon Indor;Pacen tors calvered Paving tess one ve pp `SURVIVALINDICES Pu pi++LnidVtiitacebeirstSyurIvnivdaelx:: Percent Pacer tiers ps born with at least onepupaloindvaye21 suitodnaygofaciaton Lactation nde:Porcnt pup survival fom day postculing to day 21 3 GRY ChemicalSolutions Enterprise CompanySanlDotes zNoteCodnta.in or Telomer BA : Reproduction Study Results Study Conclusion: NOEL = 25 mg/kg/day (CBI Information has been redacted A: ChemicatSluions Enterprise Company SenDoessNokeCo,te z Telomer BA : Developmental Study Results Study Conclusion: NOEL = 200 mg/kg/day CBI Information has been redacted PRL Chemical Soluions Enterprise Company SanDoies NaotdCont:ain I- = Telomer BA : Study Conclusions Subchronic -- Primary adverse target is teeth (fluoride) -- Other compound-related effects were non-adverse physiological responses : liver, kidney, thyroid + Reproduction --not a selective reproductive toxin Developmental --not a selective developmental toxin I:ChemicalSoutonsEnterprise CompanySantzed DossNolContain Telomer Ethoxylate : Chemistry F(CF,CF,),CH,CH,0H | EO CBI Information has been redacted F(CF,CF,),CH,CH,0(CH,CH,0),H + Product by Process + MixtureofMixtures : Fluorocarbon Chain and EO Chain are both gaussian distributions and tailored for specific end-uses APY: ChemicalSolutions Enterprise CompanySaTnekiDctoasrisNzoteCondta.in 16 Telomer Ethoxylate : Repeated Dose Toxicology Information + Repeated Dose Toxicity: NOEL S0mg/kg/day + Reproduction : P, NOEL = Not Established F, NOEL = 25 mg/kg/day + Developmental Toxicity: NOEL S0mg/kg/day + Genetic Toxicity: negative AMES AERChemicalStuons Enterprise ConySiDoz notC: aran * Telomer Ethoxylate : 90 Day Study Results StudyConclusion: NOEL =25 mg/kg/day CBI Information has been redacted UE: hom otuons Emre CO SME paConn Telomer Ethoxylate : Reproduction Study Results Study Conclusion: P, NOEL = Not Established F, NOEL = 25 mg/kg/day CBI Information has been redacted UB:ChemicatSluons Eneprise Company Said.Dota Coan One-Generation Reproduction Study - P1 Fertility Index (%) = # Animals that Deliver Pups # Animals that Mate + Fertility Index accounts for any event from mating to birth. + Reduction may be due to lack of fertilization, implantation or embryo viability ID: Chemica Sotutons Ener ConySanlzegDesar Conan, 4 Telomer Ethoxylate : Developmental Study Results StudyConclusion : NOEL 50 mg/kg/day CBI Information has been redacted ORDChemicalSluonsEnterprise CompanySaDo notCz onan * Telomer Ethoxylate : Study Conclusions Subchronic -- Primary adverse targets are red blood cell mass & kidney -- Other compound-related effects were non-adverse physiological responses : liver, thyroid, spleen + Reproduction -- pefufpect(sFIo)nebffleocotds aocncdukrirdendeoynly at dose levels with systemic CBI Information has been redacted Developmental -- nota selective developmental toxin SEED ChemicalSolutions Enterprise CompanySanizad. Doss NotComal po * CBI Information has been redacted EB: ChemicalSluonsEnterprise CompanySeiDzaeotdCo.an Telomer Phosphate Chemistry F(CF,CF,),CH,CH,0H | (CBI Information has been redacted [F(CF,CF,),CH,CH,0),P(O)(ONR;H); + Products by Process + BL, B Telomer Distributions tailored to end-use 5 WHR.ChemicalSolutions Enterprise `CompanySentzed. DonsNtContain 20 Telomer Phosphate : Study Update + 90 Day Repeated Dose Oral Gavage Study ~production material -- In-life complete, histopathology evaluations ongoing + Reproduction & Developmental --range-finder underway --studies to begin 1Q2002 CBI Information has been redacted CEChemicalStunsEnerprise CompanySanz,ousNot Conn Telomer Urethane Polymer : Chemistry FICFCR),CH.CHON (Tdlomer BA) ------ T2e0lo0me7r Urethane CBI Information has been redacted BE: Chemica Solutions Enterprise CompanySanz. Boa otConta , " Telomer Urethane Polymer : Repeated Dose Toxicology Information + Repeated Dose Toxicity: + Reproductive Toxicity: LOEL S0mg/kg/day (nose only) No Observed Adverse Effect at 50 mg/kg/day for all other parameters No effects on reproduction at any dose level + Developmental Toxicity: No abnormalities or birth defects + Genetic Toxicity: Negative AMES and Chom Ab PI:Chemical SolutionsEnterprise Company SankDoies NzoteCodna.n " Telomer Urethane Polymer : 90 Day Study Results Study Conclusions : + NOEL Not Established + No Observed Adverse Effect at 50 mg/kg/day for all other parameters CBI Information has been redacted SR:ChinStns Eri Copy SgComb Cort Telomer Urethane Polymer : Reproduction Study Results Study Conclusion: NOEL = 50 mg/kg/day No effects on functional reproductive parameters at any dose level CBI Information has been redacted AERChemicalStunsEneprise CompanySuDnossNa otC: arn " Telomer Urethane Polymer : Developmental Study Results StudyConclusions: + Developmental NOEL = 250 mg/kg/day + Maternal NOEL = 50 mg/kg/day (CBI Information has been redacted I mi Strnrs CSL Cr " Telomer Urethane Polymer : Study Conclusions * Subchronic -- Primary adverse effect is nasal lesions -- Other compound-related effects were non-adverse physiological responses : liver, thyroid + Reproduction ~ not a selective reproductive toxin + Developmental -- not a selective developmental toxin EI:ChemicalStunsEnerprise CompanySaDnosaNa otCo,rn a CBI Information has been redacted URE:ChemicalSluonsEvirprive CompanySuDno NiotCa:ran " 24 Fluorotelomers Exposure Assessment + In-Use Exposure Assessment + Environmental Release Assessment -- Product Trails + external focus : markets where used + distribution, use, disposal -- Mass Balance + Environmental releases & media (Land. Air, Water) GEChemicalSluinsEnerprise CompanySunita,DoesNotConan . : In-Use Exposure Model GBI Information has been redacted ChoiceSans EmreCompanySoaDoesNoConti " 25 : In-Use Exposure Model CBI Information has been redacted AB: Chemica Sluons Emerpise CompanySanze.Doms Not Cota : In-Use Exposure Model CBI Information has been redacted WHY:Chemical Solutions Enterprise `Company SanitV ied. aContain " Product Trails + For each Market / End-Use by Product + Used to determine product release points Product Trail : Carpet Finish EA | [consumer | | uu TT [Residentia|l BRD ChemicalSolutions Enterprise CompanySantEzed.eDossNtContain " CBI Information has been redacted 2 WIRY: ChemicalSolutions Enterprise CompanySaized. DotaNotSontain 27 Enviro`bnasmedeonntemailssiConos amspseassrmetntments CBI Information has been redacted GDChemical SonsEnerprise CompanySuiuz a okaCan.in a DuPont Environmental Fate & Effects Studies CBI Information has been redacted LE] [IYI [SELLE] Fate SELLE [2 WHR: ChemicalSolutions Enterprise CompanySan"iTiazecdh.cDaalssNotContain 2458 = Study Materials CBI Information has been redacted HRD: ChemicalSolutionsEirpise CompanySanaa,DoesNoCatal ss Physical - Chemical Properties 1-CF,CH,CHX, N-CgF1gCH,CHX X= OH, | UV/ Visible Absorption Spectrum Vapor Pressure Sorption + Water Solubility + Henry's Law Constant + LogK,, (Oc-tWataern Partoitilon) Chica SoursEvers CS o O GomaS Conan 5 UV-Visible Spectra : Telomer B Alcohols & lodides :g 200 3: oe EB elliaa == IT we WavelenBodin (am) iT = + No absorbance in visible light range, 350-800nm + Direct photolytic degradation not expected + Indirect Photolysis [OH Radical] work underway (8-2 Alcohol, TRP) EP ChemicalSluionsEnerprise CompanySanDosia otaCon. 5 Vapor Pressure : Telomer B Alcohols & lodides 1000 T5 22loAglicaosn] 2 Alcon 3 wo vio a ie ree ase 22 Temperature ('C) + Data fit to Antoine Equation extrapolated to ambient, 20C No anomaliesobserved I CoSomnsipnre Comoe Sl Sperone * Physical - Chemical Properties : Sorption 6-2, 8-2 Telomer B Alcohols & lodides + rapid sorption from saturated aqueous solution ~ glass, silanized glass, plastic, PTFE, stainless steel evidenceoftime-dependent adsorption with decreasing ability to recover materialfrom surfaces) + specific recovery methods had to be developed and validated ~ weeks foreach sample to reach equilibrium with continuous analysis ~ 81020 samples replicated to establish method and analysis confidence + makes water solubility measurement much more complicated and mass balances difficult to achieve HR: Chemical Solutions Enterprise CompanySanz. Doe NtCota Physical - Chemical Properties : Water Solubility 6-2, 8-2 Telomer B Alcohols & lodides pH3,7,9;T=12,25,37,60C + see no differences in solubility versus pH material is adsorbed to the container, not in the water, when excess material is no longer present ~ sorbed to the container surfaces CBI Information has been redacted HERD: ChemicalSolutionsEnterprise CompanySaza,Does No Cota 24 Physical - Chemical Properties : Water Solubility 6-2, 8-2 Telomer B Alcohols & lodides (CeF 13CH:CH:OH ic | 2c | src |e0C preliminary data : 1 range pros | ew | + De-ionized water measurements Pr---- |] o Physical - Chemical Properties : Henry's LawConstant 6-2, 8-2 Telomer B Alcohols & lodides + Computed from Water Solubility and Vapor Pressure + Non-linearity and Non-traditional behavior Surface Tension Driving Behavior? + Plan to Measure utilizing Static Headspace Method (ef. J.D. Star, tal. Analytical Chemisiry, 1993, 65, 3113-3118) SBE:ChemicalSolutions Enterprise CompanySenitzad: DossNotContain 32 2 Physical - Chemical Properties : Conclusions 6-2, 8-2 Telomer B Alcohols & lodides + Water Solubility varies with T but not pH and is in the rangeof0.1 - 1.0 ppm + Highly sorptive onto many surfaces and may remain highly sorbed and difficult to remove + Preliminary VP data do not exhibit anomalies + No visible light absorbance + These properties present sigaificant method development and analysis challenges going forward and will require use of radiolabeled material for `more studies than expected GUL Chemical Solutions Enterprise CompanySanDotnsNeotCdont:ain Analytical : Method Development Challenges + Head-Space Analysis Method -- Parent and potential degradation product(s) + Extraction & Recovery Methods _ Matrices: Soil, Sediment, Sludge, Labware Surfaces, Water _ Materials : Parent & Degradation Product(s), including radiolabel + Analysis Methods (GC/MS, LC/MS/MS) _ Parent & Degradation Product(s) in relevant matrices _ Radiolabeled Materials (stop-flow scintillation counter) SBD:Chesetumons Eiasee Cony SAE peo " Environmental Fate & Effects Work Plan Environmental Fate : Abiotic + Hydrolysis + Adsor/pDetsoirpotinon * PhysicalProperties + UV/Visible Spectrum + + AWadtesroSorlupbtitoliGitlyoasns + ACoierf-fWiactieerntPartition E+ AnnaveriobricoBinodFmeagtreaedn:atBtiioaon*tlic + AerRoobdiocapBeieoddaeegrraad)ation* CBI Information has been redacted EnvironmentalEffects + Bioconcentration Screen GED:ChemicalSluonsEneprise CORPAYSaiz Da otCoin DuPont Environmental Fate & Effects Timeline [[ees28t.m6s.m2r5,a6sA [|p]lPhysicarProperWtieesk_____g[z|aasodaraTig7p0o[0n21ai1n hileCorrean Toes ire PuckerGir} FIBAY, Sires |Screen (Minnow) WriaemiCompoSuttaearars [Brloocoomnc(enrtorawti)onFactor (BCF) . G|C2aTFotl7oCmHearCiHo2dd|eFl[AFdlsioyrapotiyoens Dasarplion(4) [Reroblc Biodegradation(tac) || [| TaTbs TontsIpeg]mif ||SAS I pPodeer eUrethane, {AnaerobicBlodegradstion rac] eps |L|T|T|T|T| RTT] pMueosder Urewomatns hane |f Anserobic Bi6e asgradation (14e C) ||Ts TTT] Meodsers" Aechre [J erosss LCT r ] This is proposed timeline and subject 10 change. ERE, Chemical SouionsEnterprise CompanySoiizad.Doe NoCota 3 72 " Conclusions + DuPont fluorotelomer-based products are safe for their intended uses. _ DuPont's data and analysis support this conclusion DuPont fluorotelomer-based products do not have the same overall PBT properties as PFOS Chemicals GO.Chemica Sluons Emeriss Conny SaDnoesNzoCon.tain @ DuPont Product Stewardship Summary + We are committed to and staying in the business. + We are confident that our products are safe for their intended uses. + We have programs in place to learn more about our products: Toxicology, Environmental Fate & Effect, Exposure + We are working together with industry members & groups + We will continue to have an open & frequent dialogue with Regulators, Customers, and Employees ERChemicalStunsEneprise COMPAY StDoaesNontCo,n ar "  Reflections & Discussion Questions Path Forward WED ChemicalSolutions Enterprise Company Senzns,Dota otSenta 3