Document 5kqLDKyjD1GyGb2MObwK5oK50

bb^So \ An zn4 _ \0i4a DuPont Product Stewardship Update United States Environmental Protection Agency 17 December 2001 R. C. Buck, G. L. Kennedy, S. H. Korzeniowski, J. C. Stadler Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCA CBI oc=> CD n? o - o <3 T i f t rv> ~ o 0 0 0 -- ip n ' m 00* 0 0 o CX> Discussion Outline Reconnect to 21 Feb Discussion Work Plans & Chemistry, Radio-label Toxicology - Biopersistence - Repeated Dose, Reproduction & Developmental Studies - Structure - Activity Relationships Exposure Connection : What the data means - Human Exposure : Worker Data, Consumer - Environmental Exposure Environmental Fate & Effects - Physical - Chemical Properties - Environmental Fate - Environmental Effects Conclusions Discussion Company Sanitized. Does Not Contain ChemicalSolutions Enterprise TSCA CBI 2 0 050 <r> --1 -a p t XT C3 ro r ~ i2 . r-o r r' 0 er5 Company Sanitized / 1 17 Dee. 2001 CBI Information has been redacted Company Sanitized. Does Not Contain 'iffiB li Chemical Solutions Enterprise TSCACBI 3 DuPont Fluorotelomer Product Groups: Intermediates, Surfactants, Polymers 1) interm ediaos SalesProducts CF2=CF2 (TFE) 17 Dec. 2001 I F(CF2CF2)nI (Telomer A) I n = 2-8 F(CF2CF2),,CH2CH2I (Telomer B) 2) S u rfa c ta n ts . "Molecules w iio iik P h o s p h u tt. (' a rh n w kiic 'ilH iH l.tll' " 'V 'in n rm . tlfifK W tu ic iii-iaitk CBI Information has been redacted F(CF2CF2)nCH2CH2OH (TelmerBA) I Straight Chain Alkyl F(CF2CF2)nCH2CH20C(0)C(R)=CH2 3t Polymers U.rxlic Ester Anude Urethane Urea Zonyl TM <r-ch,) ; Zonyl TAN <r-h) Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI 4 Synthetic Strategies for Radiolabeled Fluorotelomers 17 Dc. 2001 FX F C 7F i 5 ^ ^ ' OH November 2001 DCSE R&D Company Sanitized. Does Not Contain iS IIIt! Chemical Solutions Enterprise TSCACBI 5 General Synthetic Strategy - practical synthesis not demonstrated; SHE issues Must use readily available sources of 14C - e.g., C02(ex. BaCOj), NaCN, etc. - ample literature precedent for conversion of C=0 into CF2 - typical reagents: Et2NSF3(DAST); (MeOCH2CH2)2NSF3 (DeoxoFluoi) Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCA CBI 6 Radio-label Synthetic Routes 17 Dee. 2001 Multiple (5+) Deoxyfluorination routes explored using different starting synthons CBI Information has been redacted Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI 7 Successful Synthetic Route 17 Dec. 200i CBI Information has been redacted Synthetic Route provides access to all the key Fluorotelomer Intermediates : Telomer A, Telomer B and Telomer BA Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI g Product Stewardship Analysis How & How much? Bioavailability Exposure 17 Oec. 2001 Does it do anything? What? Where does iteo Does it persist? Risk = f (Exposure, Hazard) Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCA CBI 9 Toxicity Studies Acute Toxicitv Oral, Inhalation Eye, Skin Irritation Skin Sensitization 17 Dec. 2001 Repeat Dose Toxicitv Oral, Dermal Inhalation (AEL) Basic evaluation set Genetic Toxicitv Expanded evaluation DeveloDmental Toxicitv Reproductive Toxicitv Pharmacokinetics Company Sanitized. Does Not Contain ChemicalSolutions Enterprise TSCA CBI io Summary : In Vivo Biopersistence Screening of Fluoro- Organic Chemicals in Male Rats Purpose : To compare bio-uptake and bio-clearance in rat blood for a series of fluorotelomer intermediate, surfactant and polymeric products including PFOS as a positive control. Stu d y: 10 consecutive days dosing via oral gavage, 84 day recovery period with analysis of total Blood, Liver & 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 Company Sanitized. Does Not Contain ttH te ChemicalSolutions Enterprise TSCACBI j1 17 Dec. 2001 CBI Information has been redacted Company Sanitized. Does Not Contain 'f if f llt ! Chemical Solutions Enterprise TSCACBI 12 17 Dec. 2001 CBI Information has been redacted Company Sanitized. Does Not Contain ChemicalSolutions Enterprise TSCA CBi 13 17 Dec. 2001 CBI Information has been redacted Company Sanitized. Does Not Contain `iB H ffili Chemical Solutions Enterprise TSCA CBI 14 17 Dec. 2001 CBI Information has been redacted Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI 15 Biopersistence Studies - Key Learnings Telomer-based materials do not act like PFOS in the blood or liver - Blood total fluorine AUC's much lower than PFOS - Liver total fluorine lower than PFOS CBI Information has been redacted Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCA CBI 16 Repeated-Dose Study Plans 90 Day Subchronic Study Determine systemic effects from repeated oral gavage exposure One-Generation Reproduction Study Determine effects on parental capability to conceive, bear offspring and evaluate effects on offspring during pregnancy, early feeding and maturation to adulthood Developmental Toxicity Study Determine effects on fetal development (I.e. growth, maturation, abnormalities) Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCA CBI 17 90 Day Repeated Oral Dosing & One-Generation Reproduction Study Dose Levels : three levels + control Experimental Anim al: Male & Female CD Rats Study Evaluations : 90 Day Repeated Dose : appearance, behavior, weight, blood, organs and tissues, p-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 Company Sanitized. Does Not Contain m t l Chemical Solutions Enterprise TSCA CBI lg 90-day & One-Generation Reproduction Study Protocol Pretest " Repeat Dose Toxicity 90-day Dosing Period ____ 10 anImals/MX/dow iPretest 30 Day Recovery ^ One Month ^ 90-day Dosing Period u. Recovery a. M -----mi-------- 10 anim als/ in control and high doaa Pretest Reproductive Evaluations Jill P1 Adult Dosing Period Svamowinsis^ UMng/QMtatioa^JtMtion J F1 Adult o Evaluations D evalopm tntal Landm arks 20 anlmah/to/dMe Faces 90 Day Recovery Pretest 90-day Dosing with Blood Collection Mne 90-day Recovery with Blood Collection & 5 Dimsli/Mx/dOK Blood Fluorine S ... 81 8 18 | ChemicalSolutions Enterprise Company Sanitized. Does Not Contain TSCA CBI 19 Developmental Study Dose Levels : Three Doses + Control Experimental Animal: Male & Female CD Rats U.S. EPA Test Guidelines : 870.3700; OECD Sect. 4, No. 414 Study Evaluations : Determine effects on fetal development (I.e. growth, maturation, abnormalities) Maternal: clinical signs, body weight, gross pathology Pup: sex, body weight, external, skeletal and visceral examinations Company Sanitized. Does Not Contain ChemicalSolutions Enterprise TSCA CBI 20 DuPont Toxicology Studies Timeline 17 Dec. 2001 CBI Information has been redacted Company Sanitized. Does Not Contain 'fflH S li Chemical Solutions Enterprise TSCACBI 21 Telomer BA Synthesis Chemistry c f 2= c f 2 (T F E ) l F(CF2CF2)nI (Telomer A) n=3-6 I F(CF2CF2)nCH2CH2I (Telomer B) F(CF2CF2)nCH2CH2OH Telomer BA Straight Chain Alkyl Company Sanitized. Does Not Contain ChemicalSolutions Enterprise TSCA CBI 22 Actual Telomer BA Study Material Composition C4 C6 C8 C10 C l 2+ F(CF2CF2)nCH2CH2OH Chain Length n= Number CBI Information has been redacted Company Sanitized. Does Not Contain ChemicalSolutions Enterprise TSCACBI 23 Telomer BA : Repeated-Dose Toxicology Information F (C F 2C F 2)nC H 2C H 2O H 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 T oxicity: Negative AMES, Chrom Ab Company Sanitized. Does Not Contain <S31ISl! Chemical Solutions Enterprise TSCA CBI 24 Telomer BA : 90 Day Study Results Study Conclusion: NOEL = 25 mg/kg/day 17 Dc.200i CBI Information has been redacted Company Sanitized. Does Not Contain H ifflli Chemical Solutions Enterprise TSCACBI 25 One-Generation Reproduction Study : F1 Survival Indices O/// A*. w lasteten A5- J SURVIVAL INDICES U ttei indices Gestation Index-. Percent litters delivered having at least one live pup Utter Survival: Percent litters born with at least one pup alive on day 21 Pup indices Viability Index. Percent pups surviving to day 4 of lactation Lactation Index. Percent pup survival from day 4 postculling to day 21 uaiwpMyamaaa. umiw laiwm Chemical Solutions Enterprise TSCA CBI 76 17 Dec. 2001 Telomer BA : Reproduction Study Results Studv Conclusion: NOL = 25 mg/kg/day CBI Information has been redacted Company Sanitized. Does Not Contain U M t . Chemical Solutions Enterprise TSCACBI 27 Telomer BA : Developmental Study Results Study Conclusion: NOEL = 200 mg/kg/day CBI Information has been redacted Company Sanitized. Does Not Contain 'HEB Chemical Solutions Enterprise TSCACBI 28 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 Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI 29 Telomer Ethoxylate : Chemistry F(CF2CF2)nCH2CH2OH EO CBI Information has been redacted F(CF2CF2),,CH2CH2Q(CH2CH2Q)xH Product by Process Mixture of Mixtures : Fluorocarbon Chain and EO Chain are both gaussian distributions and tailored for specific end-uses Company Sanitized. Does Not Contain t3BS! Chemical Solutions Enterprise TSCA CBI 30 17 Dec. 2001 Telomer Ethoxylate : Repeated Dose Toxicology Information Repeated Dose Toxicity: NOEL 50mg/kg/day Reproduction: ?! NOEL = Not Established F, NOEL - 25 mg/kg/day Developmental Toxicity: NOEL 50mg/kg/day Genetic Toxicity: negative AMES Company Sanitized. Does Not Contain OE R . Chemical Solutions Enterprise TSCACBI 3] 17 Dec. 2001 Telomer Ethoxylate : 90 Day Study Results Studv Conclusion: NOL = 25 mg/kg/day CBI Information has been redacted Company Sanitized. Does Not Contain m m ChemicalSolutions Enterprise TSCACBI 32 Telomer Ethoxylate : Reproduction Study Results Study Conclusion: P, NOEL = Not Established F, NOEL = 25 mg/kg/day CBI Information has been redacted Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI 33 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 Company Sanitized. Does Not Contain ChemicalSolutions Enterprise TSCA CBI 34 17 Dsc. 2001 Telomer Ethoxylate : Developmental Study Results Study Conclusion : NOEL 50 mg/kg/day CBI Information has been redacted Company Sanitized. Does Not Contain < iH tR Chemical Solutions Enterprise TSCACBI 35 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 - pup (FI) effects occurred only at dose levels with systemic effects on blood and kidney CBI Information has been redacted Developmental - not a selective developmental toxin Company Sanitized. Does Not Contain f S & Chemical Solutions Enterprise TSCA CBI 36 17 Dec. 2001 CBI Information has been redacted Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI 37 Telomer Phosphate Chemistry F(CF2CF2)nCH2CH2OH CBI Information has been redacted [F(CF2CF2)nCH2CH20 ] xP (0)(0N R 3H)3.x Products by Process BL, B Telomer Distributions tailored to end-use Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCA CBI 38 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 Company Sanitized. Does Not Contain `SOEHB Chemical Solutions Enterprise TSCA CBI 39 17 Dee. 2001 Telomer Urethane Polymer : Chemistry F(CF2CF2)nCH2CH2OH (Telomer BA) Telomer Urethane Polymer CBI Information has been redacted Company Sanitized. Does Not Contain 'BOEHISi Chemical Solutions Enterprise TSCA CBI 40 17 Dec. 2001 Telomer Urethane Polymer : Repeated Dose Toxicology Information Repeated Dose Toxicity: Reproductive Toxicity: Developmental Toxicity: Genetic Toxicity: LOEL 50mg/kg/day (nose onlvi No Observed Adverse Effect at 50 mg/kg/day for all other parameters No effects on reproduction at any dose level No abnormalities or birth defects Negative AMES and Chom Ab Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI 41 Telomer Urethane Polym er: 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 Company Sanitized. Doee Not Contain <H1IEI& ChemicalSolutions Enterprise TSCACBI 42 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 Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI 43 Telomer Urethane Polym er: Developmental Study Results Study Conclusions: Developmental NOEL = 250 mg/kg/day Maternal NOEL = 50 mg/kg/day CBI Information has been redacted Company Sanitized. Does Not Contain ChemicalSolutions Enterprise TSCACBI 44 Telomer Urethane Polym er: 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 Company Sanitized. Does Not Contain (S B ; Chemical Solutions Enterprise TSCA CBI 45 17 Dec. 2001 CBI Information has been redacted Company Sanitized. Doaa Not Contain Chemical Solutions Enterprise TSCA CBI 46 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) Company Sanitized. Does Not Contain (SOUR ChemicalSolutions Enterprise TSCACBI 47 : In-Use Exposure Model 17 Dec. 2001 CBI Information has been redacted Company Sanitized. Does Not Contain cfiQSIS^ ChemicalSolutions Enterprise TSCACBI 48 : In-Use Exposure Model CBI Information has been redacted Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI : In-Use Exposure Model 49 17 Dee. 2001 CBI Information has been redacted Company Sanitized. Does Not Contain <Di Chemical Solutions Enterprise TSCA CBI 50 Product Trails For each Market / End-Use by Product Used to determine product release points Product T ra il: Carpet 17 Dec. 2001 Install Production DISTRIBUTION USE Company Sanitized. Does Not Contain ChemicalSolutions Enterprise TSCACBI D IS P O S A L 51 17 Dec. 2001 CBI Information has been redacted Company Sanitized. Does Not Contain < filillll Chemical Solutions Enterprise TSCACBI 52 Environmental Compartments based on emissions assessment CBI Information has been redacted Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI 53 17 Dec. 2001 DuPont Environmental Fate & Effects Studies CBI Information has been redacted Company Sanitized. Does Not Contain if f lC l Chemical Solutions Enterprise TSCACBI 54 Study Materials CBI Information has been redacted 17 Dec. 2001 Company Sanitized. Does Not Contain ChemicalSolutions Enterprise TSCA CBI 55 Physical - Chemical Properties 17 Dsc. 2001 UV / Visible Absorption Spectrum Vapor Pressure Sorption Water Solubility Henry's Law Constant Log Kow (Octanol - Water Partition) Company Sanitized. Does Not Contain 'lO H tl Chemical Solutions Enterprise TSCA CBI 56 UV-Visible Spectra : Telomer B Alcohols & Iodides No absorbance in visible light range, 350-800nm Direct photolytic degradation not expected Indirect Photolysis [OH Radical] work underway (8-2 Alcohol, TRP) Company Sanitized. Does Not Contain ChemicalSolutions Enterprise TSCA CBI 57 Vapor Pressure : Telomer B Alcohols & Iodides E E ::mz:.:ez 2 Io d id e 2 A fc o h n ; ; ; ra m k ......... l ......... 0 8 2 lo d id e " m....... 1- 9_ 2 A Ico h M "- 3 </> :i'*EE:\ 0) ........ .... * ............... a* CL a , 0 ' I::::::::::::::.::::::::.::;:: CO > 17 Dtc.2001 160 80 100 120 140 160 160 200 220 T e m p e ra tu re (C ) Data fit to Antoine Equation extrapolated to ambient, 20C No anomalies observed Company Sanitized. Does Not Contain tlllPDIti Chemical Solutions Enterprise TSCA CBI 58 Physical - Chemical Properties : Sorption 6-2, 8-2 Telomer B Alcohols & Iodides rapid sorption from saturated aqueous solution - glass, silanized glass, plastic, PTFE, stainless steel evidence o f time-dependent adsorption with decreasing ability to recover materialfrom sutface(s) specific recovery methods had to be developed and validated - weeks for each sample to reach equilibrium with continuous analysis - 8 to 20 samples replicated to establish method and analysis confidence makes water solubility measurement much more complicated and mass balances difficult to achieve Company Sanitized. Does Not Contain <BIESiS Chemical Solutions Enterprise TSCA CBI $9 Physical - Chemical Properties : Water Solubility 6-2, 8-2 Telomer B Alcohols & Iodides pH 3, 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 Company Sanitized. Does Not Contain 0 Chemical Solutions Enterprise TSCA CBI 60 Physical - Chemical Properties : Water Solubility 6-2, 8-2 Telomer B Alcohols & Iodides CeFisCHzCHaOH C8Fi7CH2CH2OH C6Fi 3CH2CH2I C8Fi 7CH2CH2I PFOA PFOS Solubility u9 / mL (ppm) 12C 25C | 37C 60C prelim inary data : 1 range 0.134 + 0.029 0.150 + 0.005 0.318 + 0.176 p re lim in a ry d a ta : 0.1 ra n g e work ongoing > w t 10 % 680 De-ionized water measurements Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI 61 Physical - Chemical Properties : Henry's Law Constant 6-2, 8-2 Telomer B Alcohols & Iodides Computed from Water Solubility and Vapor Pressure Non-linearity and Non-traditional behavior Surface Tension Driving Behavior? Plan to Measure utilizing Static Headspace Method (ref. J. D. Stuart, etal., Analytical Chemistry, 1993, ,3113-3118) Company Sanitized. Does Not Contain 'tfflB li ChemicalSolutions Enterprise TSCACBI 62 Physical - Chemical Properties : Conclusions 6-2, 8-2 Telomer B Alcohols & Iodides Water Solubility varies with T but not pH and is in the range of 0.1 -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 significant method development and analysis challenges going forward and will require use of radiolabeled material for more studies than expected Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCA CBI 63 Analytical : Method Development Challenges Head-Space Analysis Method - Parent and potential degradation produces) Extraction & Recovery Methods - Matrices: Soil, Sediment, Sludge, Labware Surfaces, Water - Materials : Parent & Degradation Produces), including radiolabel Analysis Methods (GC/MS, LC/MS/MS) - Parent & Degradation Product(s) in relevant matrices - Radiolabeled Materials (stop-flow scintillation counter) Company Sanitized. Does Not Contain < 6 E Chemical Solutions Enterprise TSCA CBI 64 17 Dec. 2001 Environmental Fate & Effects Work Plan C Environmental Fate : Abiotic Hydrolysis Adsorption / Desorption * Physical Properties UV/Visible Spectrum Water Solubility Environmental Fate : Biotic Adsorption to Glass , Anaerobic Biodegradation* Air-Water Partition Aerobic Biodegradation* Coefficient ( * R a d io lab eled M a te ria l) CBI Information has been redacted Environmental Effects Bioconcentration Screen Company Sanlt zfcd. Does Not Contain Chemical Solutions Enterprise TSCA CBI 65 DuPont Environmental Fate & Effects Timeline 17 Dc. 2001 CBI Information has been redacted Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI 66 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 Company Sanitized. Doe* Not Contain <511!! Chemical Solutions Enterprise TSCA CBI 67 Conclusions DuPont fluorotelomer-based products are safe for their intended uses. - DuPont's data and analysis support this conclusion DuPont fluorotelomer-based products d o n o t have the same overall PBT properties as PFOS Chemicals Company Sanitized. Does Not Contain m m Chemical Solutions Enterprise TSCA CBI 68  Reflections & Discussion Questions Path Forward 17 Oec. 2001 Company Sanitized. Does Not Contain Chemical Solutions Enterprise TSCACBI 69