Document 3JOLymn14oZbj61dwGDoBQ8JD

( R R 9 .3 - & -4 R i i & - \ & C Ce: S. Korzeniowski - DuPont K. Smythe - Rand M. Dominiate - U.S. EPA mm Chemical Solutions Enterprise 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 January 31, 2002 To Whom It May Concern:, Please find enclosed an updated copy of the Telomer Research Program presentation submitted to the Agency at the meeting held on December 18,2001. The CBI claim for the information on pages 37 and 63 is withdrawn. These pages contain no CBI and should be included in the public record. Text has been added to pages 37 and 63 to clarify that the proposed timelines are subject to change. Otherwise, these pages do not differ in any other way from the documents that were provided on December 18, 2001. In addition, a typographical error on page 31, replacing the word "Liver" with the word "Kidney" has also been made on both the CBI and non-CBI versions. The non-CBI version of this document is intended to replace the previous version (AR226-1044) in the public record. Please contact me if you have any questions regarding this submission. Best regards, <rM td C ^ y ^ Robert C. Buck, Ph.D. Sr. Technology Consultant Phone: 302.892.8935 Fax : 302.892.1124 Email : robert.c.buck@usa.dupont.com 63020000012/0 G 30S 000001E /0 r*o crro.* O zo I "~Gopo i --i P"l T3 oO CJ ICTr't co ... I iLI* i 17 Dec 2001 Telomer Research Program Update and Status Report United States Environmental Protection Agency 18 December 2001 Telomer Research Program Company Sanitized. Does not Contain TSCA CBI Agenda 17 Dec 2001 TRP General Update; TRP Meetings Radio-label Update Pharmacokinetics Toxicology & Descriptive Biology Environmental Fate & Effects Summary Discussion and Path Forward Telomer Research Program Company Sanitized Company Sanitized. Does not Coni TSCA CBI X 17 Dec 2001 TRP Review with U S EPA - 21 Feb. 2001 Toxicology Program Status & Timing Environmental Fate & Effects Program, Protocols, & Timeline Radiolabel Material Status, Timeline Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 3 17 Dec 2001 Telom er Research Program (TRP) : 2001 Key E vents - January 9, 2001 : Environmental Fate & Effects Research Team Meeting - February 21, 2001 : U.S. EPA - March 9, 2001 : METI - March 20-22, 2001 : TRP Meeting, Osaka - April 19, 2001: Environment Canada - May 16-17, 2001 : Environmental Fate & Effects Research Team Meeting - May 18, 2001 : U.K. Environment Agency - June-September 2001: Sub-team meetings and Conference Calls - October 31 - Nov. 2, 2001 : TRP Meeting, Frankfurt Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 4 3 TRP Osaka Meeting Highlights 20-22 March 2001 17 Dec 2001 Updates on 8-2 Alcohol Starting Material and Quality Radio-label Synthesis Strategic Plan and Path Forward TRP Database Status Review and Upgrades to Toxicology and Pharmacokinetics Plans Review and Upgrades to EF&E Work Plans: Tier I, II, III Communications Team Work Plan Telomer Research Program Company Sanitized. Poes not Contain TSCACBI 5 TRP Frankfurt Meeting Highlights 31 October - 2 November 2001 17 Dec 2001 Toxicology Data Review and Subsequent Upgrades to Overall Tox Plans; Review Data to Date and Scheduling Radio-label Synthesis Review, Sourcing Plan, and Timing Pharmacokinetics Plans due to Radio-label Schedule Analytical Effort Overview and Challenges EF&E Tier I and II Workplan Updates and Revisions; Review Data to Date and Scheduling Workplan for Compounds Beyond 8-2 Alcohol TRP Sponsorship of Outside Research Communication Strategy and Path Forward Next Meeting(s): Conference Calls and In Person Telomer Research Program Company Sanitized. Does not Contain TSCACBI 6 17 Dec 2001 CBI has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCACB1 n-C8F17CH2CH2OH Analysis Profile Purity > 99% by G.C. - 99.2% n-C8F 17CH2CH2OH - no other CnF2n+1CH2CH2OH species - 0.8% impurity CBI has been redacted 7 17 Dec 2001 Telomer Research Program Company Sanitized. Does not Contain TSCACBI r g 4 n-C8F17CH2CH2OH Selection Criteria 17 Dec 2001 Selection Criteria Included: Simple, Single, Pure, Representative, and Readily Characterized Most Common and Representative from Each of 5 Major ProducersIncludes Both Type and Chain Length Telomer 8-2 Alcohol - F(CF2CF2)4-CH2CH2-OH - Was Chosen To - Be Able to Characterize a Single Compound versus a Complex Product Mixture - Enable the Research Team to Study Metabolites in the Pharmacokinetics Work (ADME) - Study the Degradation Products and Locations in the Environmental Fate Studies - Enable the Team to Measure Critical Physical Property Data - Enable the Team to Radio-label a Single Key Compound for the Toxicology and Environmental Fate Studies Telomer Research Program Company Sanitized. Does not Contain TSCACBI 9 n-C8F17CH2CH2OH Selection Criteria 17 Dec 2001 Due to the Complexity and Non-Classic Behavior of the Fluorochemicals, Numerous Testing Protocols Had to be Developed and Validated. By Definition, a Single Compound was the Only Viable Alternative that Held Prospects to Gain Significant and Interpretable Results of Common Value The Ability to Analyze Products, By-Products, Metabolites, and Attain Low Detection Limits Drove the Research Team to a Single Representative Molecule, Not a Product Mixture Products from the 5 Major Producers Do Share Some Similarities But are for the Most Part Different Protocols Developed by the TRP Research Team Will Have Broad Applicability for Use by TRP Members on Other Compounds and Products of Their Choice and Relevant to their Company CBI has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 10 & 5 Radiolabeled 8-2 Tetomer B Alcohol 17 Dec 2001 F(CF2)714CF2-c h 2c h 2-o h Needed for Pltartuacoktiii < i- I nenonm ental fa te Studies Status Synthetic Route Demonstrated & Reproducible : can put ,4C "in" Necessary Documentation & Samples being finalized Partner identified to accomplish hot synthesis Timing to completion: March 2002 Telomer Research Program Company Sanitized. Does not Contain TSCACBI ]1 Synthetic Strategies for Radiolabeled Fluorotelomers 17 Dec 2001 C tF is^ ^ ^ O H RF C77rF15 December 2001 Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 12 7 6 General Synthetic Strategy 17 Dec 2001 - practical synthesis not demonstrated; SHE issues * Must use readily available sources of 14C - e.g., C 0 2 (ex. BaCOj), NaCN, etc. - ample literature precedent for conversion o f C = 0 into CF2 - typical reagents: Et2NSF3 (DAST); (MeOCH2CH2)2NSF3 (DeoxoFluor) Telomer Research Program Company Sanitized. Does not Contain TSCACBI 13 17 Dec 2001 CBI has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCACBI 8 14 7 17 Dec 2001 CB I has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 15 17 Dec 2001 CBI has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 16 17 Dec 2001 CBI has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCACBI 17 17 Dec 2001 CBI has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCACBI IO 18 9 17 Dec 2001 CBi has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCACBI 19 17 Dec 2001 CBI has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCACBI 20 17 Dec 2001 CBI has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCACBI 21 17 Dec 2001 CBI has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 22 17 Dec 2001 CBI has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCACBI 23 17 Dec 2001 CBI has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCACBI 13 24 12 Radiolabel Path Forward F(CF2)714CF2-c h 2c h 2-o h 17 Dec 2001 C hem ical Synthesis M ethods P a c k a g e out fo r Bid A nalytical M ethods C old S tandards 13C M aterial as Standard 1 4 C Study M aterial D elivery 2001 Dec Jan 2002 Feb M ar Telomer Research Program Company Sanitized. Does not Contain TSCACBI 25 TRP Toxicology Studies 17 Dec 2001 Repeated-Dose Pilot Study - Rats 8-2 Alcohol Objective : To determine test concentration for 90-Day toxicity study A) In vivo response B) Attain steady-state blood fluorine levels Procedure : Dose Groups* of rats with 0, 5, 25 or 125 mg/kg/day of 8-2 Telomer Alcohol A) Monitor clinical observations, weigh rats 2x/week B) Total blood fluorine analysis weekly * 10 males, 5 females / group Telomer Research Program Company Sanitized. Does not Contain TSCACBI 26 l 13 TRP Toxicology Studies Repeated-Dose Pilot Study - Rats 8-2 Alcohol Results - Clinical Observations 17 Dec 2001 125 mg/kg/day - Males: striped teeth (7/10), teeth clipped (4/10) - Females : striped teeth (4/5) No Effects : 5 - 25 mg/kg/day Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 27 TRP Toxicology Studies Repeated-Dose Pilot Study - Rats 8-2 Alcohol Results - Body Weight Gains Dose Level (me/ke/dav) Males Females 0 297 80 5 288 119 25 275 115 125 238* 110 * p<0.05 Telomer Research Program Company Sanitized. Does not Contain TSCA CBI ir 28 14 17 Dec 2001 Mean Body Weight for Males (Day 0 - 81 ) Telomer Research Program Company Sanitized. Does not Contain TSCACBI 29 TRP Toxicology Studies Repeated-Dose Pilot Study - Rats 8-2 Alcohol Results - Liver Weight / Ratios 2001 Dose Level (m g/kg/dav) 0 5 25 125 Liver Weight (g) M _z 23.4 10.3 21.1 11.1 22.7 11.3 27.9 12.7 Liver/Body Weight g /100g MF 3.9 3.2 3.7 3.2 4.1 3.4 5.5* 3.6* 0.05Telomer Research Program * p < Company Sanitized. Does not Contain TSCACBI 30 6 15 TRP Toxicology Studies Repeated-Dose Pilot Study - Rats 8-2 Alcohol Results - Kidney Weight / Ratios Dose Level im e/ke/davi 0 5 25 125 Liver Weight (g) M _E 4.5 2.2 4.3 2.4 4.1 2.4 4.4 2.7* Kidney/Body Weight g/100g MF 0.76 0.70 0.76 0.71 0.75 0.73 0.87 0.78* Telomer Research Program * p < 0 . 0 5 Company Sanitized. Does not Contain TSCACBI 31 17 Dec 2001 Total Blood Fluorine Analysis in Male Rats Dosed with Telomer 8-2 Alcohol Telomer Research Program Company Sanitized. Does not Contain ___ TSCA CBI 17 32 1 17 Dec 2001 Total Blood Fluorine Analysis in Female Rats Dosed with Telomer 8-2 Alcohol TSCA CBI Repeated-Dose Pilot Study 17 Dec 2001 Analysis of Pooled Plasma Samples Obtained at Steady State (test day 84) (PFOA, Parent Compound, and total fluorine levels) The level of parent detected did not exceed 0.074 ppm in either males or females. The following plasma levels of PFOA were detected in males and females dosed with 0, 5, 25, and 125 mg/kg/day of 8-2 Telomer Alcohol Dose (mg/kg/day) Male PFOA (ppm) Male PFOA converted to ppm F Male total plasma F (ppm)a Female PFOA (ppm) Female PFOA converted to ppm F Female total plasma F (ppm)a 0 0.07 0.05 NM 0.0 0.0 NM 5 2.19 1.51 NM 0.08 0.05 NM 25 8.47* 5.83 8.11 0.54 0.37 5.88 125 65.60* 45.16 53.24 1.85* 1.27 23.2 "Determined using Wickbold Torch; *mean of two separate runs; NM-not measured Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 34 TRP Toxicology Studies Repeated-Dose Pilot Study - Rats 8-2 Alcohol 125 mg/kg/day 8-2 Telomer Alcohol Produces clinical effects / body weight effects Blood Fluorine level reached plateau day 50<-->80 Degree o f response compatible with adequate survival 5 - 25 mg/kg/day Telomer Alcohol N o clinical signs or weight effects Blood fluorine level reaches plateau day 40<-->60 N o signs of adverse response 90-Day Test Levels (suggested) 1 - 5 -2 5 - 125 mg/kg/day Telomer Research Program Company Sanitized. Doea not Contain TSCACBI 17 Dec 2001 35 TRP Toxicology Studies 17 Dec 2001 Repeated-Dose Pilot Study Conclusions Analysis limited to blood only - Significant male/female differences - Results confirm earlier studies results - Other metabolites are present & predominate in females - There is a significant amount of fluorinated organic material eliminated or elsewhere Validates need to conduct pharmacokinetic studies as planned with radiolabeled study material Telomer Research Program Company Sanitized. Doea not Contain TSCA CBI 36 17 Dec 2001 TRP Toxicology and Descriptive Biology Studies: Timeline* Test Material 8-2 Alcohol TRP W ork = Work Contracted 2001 2002 2003 Contract W ork Acute Oral Ranae-Findina Oral Toxicrtv 1Q 2Q 3Q 4Q 1Q 20 3Q 40 10 2Q 3Q 40 Lab Haskell Haskell Subchronic 90 Day Gavage (Rat) w1 recoverv Haskell Multigeneration Reproduction LBatl_________________________ Developmental Toxicitv (Rat) Bacterial Reverse Nhitation Haskell Haskell Covance Bone Marrow Erythrocyte Micronucleus Test (Rat) Covance Telomer Research Program * This is a proposed timeline and subject to change. Company Sanitized. Does not Contain TSCA CBI 37 17 Dec 2001 TRP Pharmacokinetics Studies: Timeline v = Work Contracted Test Material 8-2 Alcohol TRP Work Work s ADME Mass Balance In Vitro Metabolism (m icrosom es) In Vitro Metabolism (hepatocytes) 2002 2003 Contract 1 0 2 0 3 0 4 0 102Q 3Q 4Q Lab Haskell Haskell Haskell Only Haskell Lab bid on entire package and will conduct the work Start of studies delayed 6+ months due to radio-label synthesis Telomer Research Program ___ Company Sanitized. Does not Contain TSCA CBI 3g O 19 TRP Pharmacokinetics Study Radiolabeled Fluorotelom er Alcohol 14C Label In perfnoro-cham (C #3) F(CF2)714CF2-c h 2c h 2-o h 17 Dec 2001 Telomer Research Program Company Sanitized. Does not Contain TSCACBI 39 TRP Pharmacokinetics Study 17 Dec 2001 Toxicokinetics of Telomer 8-2 Alcohol in the Rat - The objectives o f this study are to determine the Absorption, Distribution, Metabolism and Excretion (ADME) o f Telomer 8-2 Alcohol in male and female rats following oral and dermal dosing. Telomer Research Program Company Sanitized. Does not Contain TSCACBI 40 TRP Pharmacokinetics Study 17 Dec 2001 Toxicokinetics of Telomer 8-2 Alcohol (TBA) in the Rat Objective: Determine the absorption, distribution, metabolism and excretion o f Telomer 8-2 Alcohol in male and female rats following oral and dermal dosing Method: * Conduct pilot experiments ** Radiolabeled and cold TBA used as test material ** 2 male and 2 female rats ** Determine plasma kinetics following a single high oral dose o f TBA ** Determine excretion and metabolism following a single high oral dose o f radiolabeled TBA * Conduct absorption experiments ** TBA test material ** 4 male and 4 female rats ** Single low and single high oral dose * * Single low and single high dermal exposure (8 hrs) ** Single low intravenous dose ** Follow plasma concentrations o f test material Telomer Research Program Company Sanitized. Does not Contain TSCACBI 41 TRP Pharmacokinetics Study ''Dec 2001 Toxicokinetics of Telomer 8-2 Alcohol (TBA) in the Rat (Continued) * Distribution experiments ** Radiolabeled TBA test material ** 4 male and 4 female rats ** Conduct oral and dermal exposures ** Evaluate tissue distribution of test material at Tmax and Tmax/2 * Excretion and metabolism experiments ** Radiolabeled TBA test material ** 4 male and 4 female rats ** Single low and high oral doses ** Single low and high dermal doses ** Daily dose of TBA with last dose being radiolabeled TBA ** Identify excretion rates and metabolic profiles Results: * Metabolic profiles of TBA * Qualitative and quantitative description of biodistribution of TBA * Description of absorption characteristics of TBA * Sex linked differences in TBA handling in rats * Description of TBA metabolism at varying concentrations and between sexes Telomer Research Program Company Sanitized. Does not Contain TSCACBI 42 17 D ec 2001 TRP Pharmacokinetics Study In Vitro Microsomal Metabolism Study - The objective of this study is to determine the rate of metabolism of a test compound in microsomes prepared from livers of a number of species (normally rat, rabbit, dog, monkey, and human) and to identify the metabolites produced in each species. Metabolism of Telomer 8-2 Alcohol by Mammalian Hepatocytes - The objective of this study is to determine the rate of metabolism of a test compound in cultured liver cells prepared from a number of species (normally rat, rabbit, dog, monkey, and human) and to identify the metabolites produced in each species. Telomer Research Program Company Sanitized. Does not Contain TSCACBI 43 TRP Pharmacokinetics Study 17 Dec 2001 Metabolism of Telomer 8-2 Alcohol by Mammalian Microsomes Objective: Determine the rate of test material metabolism and metabolic product identification in liver microsomes prepared from several mammalian species. Method: * Microsomes prepared from rat, rabbit, dog, monkey and human * Samples analyzed by HPLC-MS * Determine linearity of reaction rate and protein concentration ** Reaction media contains an NADP regeneration system, cofactors, microsomes, test compound and phosphate buffer at pH 7.4, 37C ** Determines kinetics of test compound ** Reactions carried out at constant initial test material concentration and at a constant protein concentration ** Time course metabolism by microsomes evaluated Results: * Rate of microsomal metabolism o f test compound by each species tested * Identity of metabolic products * Estimates of test material half-life in-vitro and intrinsic clearance Telomer Research Program Company Sanitized. Does not Contain TSCACBI 44 TRP Pharmacokinetics Study 17 Dec 2001 Metabolism of Telomer 8-2 Alcohol by Mammalian Hepatocytes O bjective: To evaluate the rate o f metabolism and identification o f metabolic products in cultured liver cells from several mammalian species. Method : Prepare hepatocytes from rat, mouse, rabbit, monkey, dog and human Negative (vehicle) and positive (ethoxycoumarin) controls included Hepatocytes and compound incubated at 37C for 2 hrs Samples analyzed by HPLC-MS for test compound and metabolites R esu lts: Qualitative and quantitative description o f metabolic activity toward test material in several species Description o f metabolism in a metabolically "complete" system Identity o f test material metabolites in a whole cell system Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 45 TRP Pharmacokinetics Study 17 Dec 2001 Developm ent of a Biologically-Based Kinetic Model: Objective: - Quantitatively Relate Exposure to Internal Dose Using a Biologically-based Kinetic Model Critical Information Requirements: - Partitioning in Biological Tissue - Qualitative and Quantitative Aspects of Biotransformation - Mass Balance and Biodistribution - Uptake and Elimination Kinetics Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 46 TRP Toxicology Studies 17 Dec 2001 Developmental Toxicity - Rats 8-2 Alcohol Status: Initiate 3Q 2002 Pregnant rats Dose days 6-19 of gestation Doses from 90-day study (project 1<--> 1 0 ,10<-->50, 50<-- >125 mg/kg) Maternal parameters - clinical signs, body weights, liver weight Fetal parameters - external examination, internal organ examination, liver weight, skeletal examination Compare maternal/fetal response Telomer Research Program Company Sanitized. Does not Contain TSCACBI 47 TRP Toxicology Studies 17 Dec 2001 Acute Toxicity - Rats 8-2 Alcohol Status: Completed Rat - Male and Female - 5/sex/group - Single oral dose o f 2,000 mg/kg (0.5% aqueous methylcellulose) - Results No mortality No clinical signs including body weight Lethal dose >2,000 mg/kg Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 4g TRP Toxicology Studies 90-Day Toxicity Study - Rats 8-2 Alcohol 17 Dec 2001 Additions to Protocol 1. Test levels (4 instead o f 3) 1, 5 ,2 5 , and 125 mg/kg 2. Extend recovery period - 90 days 3. Add measure o f peroxisome proliferation - P-oxidation 4. Add thyroid weights, plasma and urinary [F] Telomer Research Program Company Sanitized. Does not Contain TSCACBI 49 TRP Toxicology Studies 17 Dec 2001 Genetic Toxicity 8-2 Alcohol Status: Draft Reports Salmonella/Escherichia coli Assay TA 98, TA 100, TA 1535, TA 1537 WP2uvrA With/without S9 activation To 5,000 pg/plate Negative (draft report to issue 12/01) Telomer Research Program Company Sanitized. Does not Contain TSCACBI so TRP Toxicology Studies Genetic Toxicity 8-2 Alcohol In Vivo Rat Micronucleus Study 0, 500, 1,000, 2,000 mg/kg single dose oral gavage 6 male rats/group (examined 5) - harvest at 24 and 48 hours 60 mg/kg cyclophosphamide positive control Micronucleated cells/2000/animal Dose (mg/kg! 24 hrs 48 hrs 0 0.04 0.07 CP-60 3.10 0.78 8-2 Alcohol - 500 0.04 0.09 -1000 0.15 0.09 -2000 0.10 0.09 * Conclude: No increase in micronucleated cells (draft report available 12/5/01) Telomer Research Program Company Sanitized. Does not Contain TSCACBI 17 Dec 2001 si TRP Toxicology Studies 17 Dec 2001 Reproductive Toxicity - Rats Multigeneration Reproduction - 8-2 Alcohol Status: Pending Outcome o f 90-Day Study/Developmental Toxicity Rat - dosing levels/control - treat 70 days pre-mating - 2nd generation from F 1 offspring Parameters - estrous cycling/sperm assessment - fertility/reproductive function - gestational/lactational performance - pup growth/survival/structural integrity - P I/F I parental pathology (focus on reproductive system) Telomer Research Program Company Sanitized. Does not Contain TSCACBI 52 17 Dec 2001 TRP Environmental Fate & Effects Studies Physical - Chemical Properties Environmental Fate Environmental Effects Bioconcentration Telomer Research Program Company Sanitized. Does not Contain TSCACBI 53 Physical - Chemical Properties n-C8F17CH2CH2OH UV / Visible Absorption Spectrum Vapor Pressure Sorption Water Solubility Henry's Law Constant Log K ow (Octanol - Water Partition) 17 Dec 2001 Telomer Research Program Company Sanitized. Does not Contain TSCACBI 54 UV-Visible Spectra : n-C8F17CH2CH2OH 17 Dec 2001 A b s orbance/N anom e te rs File #1 010681 .CSV TEL 66 -2A4.323G J- MEOH 1CM KAISER,M6,, Paged Y-Zoom CURSOR Res=None No absorbance in visible light range, 350-800nm Direct photolytic degradation not expected Indirect Photolysis [OH Radical] work underway Telomer Research Program Company Sanitized. Does not Contain TSCACBI 55 Vapor Pressure : n-C8F17CH2CH2OH 17 D ec 2001 0.022 Torr at 21 C Telomer Research Program Tem perature (C) Company Sanitized. Does not Contain TSCACBI 56 28 Physical - Chemical Properties : Sorption n-C8F17CH2CH2OH 17 Dec 2001 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 surface(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 Telomer Research Program Company Sanitized. Does not Contain TSCACBI 57 17 D e c 2001 Physical - Chemical Properties : Water Solubility n-C 8F 17C H 2C H 2OH 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 longerpresent - sorbed to the container surfaces CBI has been redacted Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 30 5g 29 Physical - Chemical Properties : Water Solubility n-C8F17CH2CH2OH 17 Dec 2001 C 8F 17C H 2C H 2 0 H APFO PFOS Solubility ug / mL (ppm) 12C 25C 37C 60C 0.134 + 0.029 0.150 i 0.005 0.318 0.176 > 10 wt% 680 De-ionized water measurements T doraer Research Program Company Sanitized. Does not Contain TSCACBI 59 17 D ec 2001 Physical - Chemical Properties : Henry's Law Constant n-C8F17CH2CH2OH Computed from Water Solubility and Vapor Pressure Non-linearity and Non-traditional behavior Surface Tension Driving Behavior? Measure utilizing Static Headspace Method Telomer Research Program Company Sanitized. Does not Contain TSCACBI 3! 60 30 Physical - Chemical Properties : Conclusions n-C8F17CH2CH2OH 17 Dec 2001 Water Solubility varies with T but not pH and is in the 100's of ppb 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 m ethod developm ent and analysis challenges goin g forward and will require use o f radiolabeled material for more studies than expected Teloraer Research Program Company Sanitized. Does not Contain TSCA CBI 6\ Environmental Fate & Effects Work Plan 17 Dec 2001 n-C8F 17CH2CH2OH r Environmental Fate : Abiotic Hydrolysis Adsorption / Desorption * Physical Properties Indirect Photolysis in Air UV/Visible Spectrum Water Solubility Adsorption to Glass Air-Water Partition Coefficient < Environm ental Fate : Biotic Anaerobic Biodegradation* Aerobic Biodegradation* (* Radiolabeled Material) Telomer Research Program Environmental Effects Bioconcentration Factor 90 Day Early Life Stage Study - Rainbow Trout *21 Day Invertebrate Daphnia Study Company Sanitized. Does not Contain TSCA CBI 62 17 Dec 2001 TRP Environmental Fate & Effects Studies Timeline* F = Fate Study ; E = Effects Study P = Physical Property Study Test Materials Work 8-2 Alcohol EJ Hydrolysis F Adsorption / Desorption ( 1 4 0 F Aolna / Seauestration ( 1 4 0 T R P W ork F Aerobic Biodegradation (1 4 0 F Anaerobic Biodegradation ( 1 4 0 F Indirect Photolysis in Air I2001 3Q14Q11 a 2002 2003 3Q 4Q !IQ 2Q 3Q 4Q p illi : CNR5 B r~ E Acute Fish : Fathead Minnow E Acute Invertebrate : Daphnia r n a q n a I Biological Concentration Factor (BCF) 1140 F 90 Day Rainbow Trout Chronic E 21 Day Daphnia Magna C h r o n ic E 7 2 Hr Algae Acute & Chronic I F W ater Solubility. Vo. Sorption p Henry's Law Constant Li HI I L : :l zj i [ _ __ 1 1 Telomer Research Program * This is a proposed timeline and subject to change. Company Sanitized. Does not Contain TSCACBI 63 TRP Path Forward Items 17 Dec 2001 Toxicology & Descriptive Biology Pharmacokinetics Radiolabel Environmental Fate Environmental Effects Mass Balance Effort Telomer Research Program Company Sanitized. Does not Contain TSCACBI 64 17 Dec 2001 Discussion and Path Forward Telomer Research Program Company Sanitized. Does not Contain TSCA CBI 65