Document 2RjOkJYV2YLr2wZxwjL6kNVx5

whpp AR 226_ 1033 QP DuPont Chemical Solutions Enterprise MR# 5354] Bens Viirson 5 em 03 September 24, 2001 Karen Lannon US. EPA, OPPTS 4Do0c1uMmeStnrteeCt,onSt.rWo.l (CeTnSt-e7r407) `Washington, DC 20460 AR 326 6 2z0 o lo(00000 15 ~ 8 3 om Reference: AR266 [i Dear Ms. Lannon: SE have once again prepared authentic sanitized copiesofthe two presentations we gave'on February 21, 2001. A paper copyofeach presentation is enclosed for the public record. These presentations are as follows: "DuPont Research Program Update and Status Report"- February 21, 2001 and "Telomer Research Program Update and Status Report" - February 21, 2001 Each of these reports has been company sanitized. They do not contain TSCA CBI. Each IannfdoervmeartyiocnhahratsthbaetehnarsehdaacdteCdB."I removed has been marke: with the following note: "CBI cPlaenarseeacleht mmeevkinaopwhoinfeyoonu (h3a0v2e)9a9n2y-3ad6d7i2tioornaflaxquoenst(i3o0n2s)8o9n2-t1h1e3s5e. twMoydoecmuamilenatdsd.resYsoius stephehn korzeniowski@usa.dupont.com. 2 `With regards, IGE AvSaHcKhAmIenot ." MStaerpkheetn&H.BuKsoirnzeesnsioMwasnkaige~r~ =--, Company Sanitizeq ! Telomer Research Program Update and Status Report 5 3 Presented to U.S. EPA, OPPT z 21 February, 2001 f "Telomer Research Program Feb, 2001 "Company Sanitized. Does Not Contain TSCA CBI" 1 2 | TRP Member Companies | Asahi Glass | Atofina Clariant | Daikin * DuPont Telomer Research Program Feb, 2001 "Company Sanitized. Does Not Contain "TSCA CBI" 2 3 Agenda TRP Toxicology & Descriptive Biology Pharmacokinetics Radiolabel Environmental Fate Environmental Effects TRP Database * Summary Telomer Rese Progam Peo 2000 "Company Sanitized. Does Not Contain TSCA CBI" 3 4 | Telomer Research Program (TRP) Key Events Timeline -- June 20, 2000 : Formal Organization Proposal -- July 7, 2000 : Met with U.S. EPA -- July 11, 2000 : Met with METI -- August 14-15, 2000 : First Meeting as Formal Consortium, Toxicology Planning ~ October 23, 2000 : Present Update to U.S. EPA ~ October 30, 2000 : Present Update to METI -- January 9, 2001 : Environmental Fate & Effects Research Team Meeting -- February 21, 2001 : Next U.S. EPA Meeting -- March 2, 2001 : Next METI Meeting -- March 20-22, 2001 : TRP Mecting Toomer Research Program Feb. 2001 "Company Sanitized. Does Not Contain TSCA CBI" 4 5 TRP Review with U.S. EPA : 23 Oct. 2000 + TRP Members, Principles, Structure, Processes + Chemical to be tested : n-CgF,CH,CH,0H ~ Toxicology and Descriptive Biology Studies : Protocol Review ~ Pharmacokinetics Studies : Protocol Review ~ Radiolabel Work ~ Environmental Fate Outline ~ Overall Timeline Path Forward Items Telomer Research Program Feb. 2001 "Company Sanitized. Does Not Contain TSCA CBI" 5 6 U.S. EPA Comments & Feedback : 23 Oct 2000 + Develop communication plan : Deliver the same message to other Global Regulatory Agencies (OECD, MITI, UK DETR, Environment Canada, etc.) + Program is very well designed. Like Pharmacokinetics focus. + 8-2 Telomer Alcohol as study compound accepted. + TRP should consider multiple species (> 2) for developmental toxicology work. + Biodegradation studies are an important area; use radiolabeled material. + Environmental Fate & Effects work is critical. Start soon evenif phased in. Want to review program when methods are complete. Feb 2001 target. Telomer Research Program Feb. 2001 "Company Sanitized. Does Not Contain TSCA CBI" 6 7 TRP Chemical to be Tested Telomer 8-2 Alcohol: | n-CF,,CH,CH,0H * Purity >99%, and characterized + Sample made, 20 kg elon ops roger Fo 200 "Company Sanitized. Does Not Contain TSCA CBI" 7 | n-C4F,,CH,CH,OH Analysis Profile Purity > 99% by G.C. ~ 99.2% n-CF,CH,CH,0H --no other C,F,,,,CH,CH,OH species -- 0.8% impurity CBI Information has been redacted Telomer Research Program Feb. 2001 "Company Sanitized. Does Not Contain TSCA CBI" 8 9 TRP Toxicology and Descriptive Biology Studies : Timeline CBI Information has been redacted Felomer Research Progam Feb 2001 "Company Sanitized. Does Not Contain TSCA CBI" ' oo | TRP Toxicology and Descriptive Biology Studies Acute Oral Toxicity - Fixed Dose Method -Objective: to assess acute oral toxicity from administration of compound to rats by oral gavage + Repeated-Dose Oral Toxicity Gavage Range-Finding Study in Rats -Objective: to determine appropriate dose levels for use in a 90-day oral subchronic study Felomer Reseach Program Feb, 2001 "Company Sanitized. Does Not Contain TSCA CBI" 10 " TRP Toxicology and Descriptive Biology Studies + Subchronic Toxicity: 90-Day Gavage Study in Rats with Recovery Objective: to evaluate the potential subchronic toxicity and reversibility of toxicity and concentration of parent compound and metabolites in the blood when 8-2 alcohol is administered to male and female rats. The oral route of administration was selected because it provides a controlled and effective means of compound delivery. Telomer Research Program Feb, 2001 "Company Sanitized. Does Not Contain TSCA CBI" 12 | n | TRP Toxicology and Descriptive Biology Studies + Developmental Toxicity Study in Rats ~The purpose of this study is to evaluate thedevelopmental toxicity of Telomer 8-2 alcohol, administered by gavage, to pregnant rats from the time of implantation to the end of gestation. Tomer Research Program Feb, 2001 "Company Sanitized. Does Not Contain TSCA CBI" 12 13 | TRP Toxicology and Descriptive Biology Studies + Multigeneration Reproduction Study in Rats ~The objective of this study is to evaluate the effect of Telomer 8-2 alcohol on the gonadal function, conception, parturition, and the growth and development of offspring of male and female Crl:CD(SD)IGS BR rats over two generations involving the production of at least one set of litters in each generation Telomer Research Program Fe, 201 "Company Sanitized. Does Not Contain TSCA CBI" 13 1H TRP Toxicology and Descriptive Biology Studies + Bacterial Reverse Mutation Test with an Independent Repeat Assay ~The purpose test substance of by this study is to measuring its evaluate ability to the mutagenic induce reverse potential of the mutations at tserlyepcttoepdhalonciloofcsuesvoefrEaslchsterraiicnhsioafScaollimoWnPe2lluavtryApihnimtuheripurmesaenndceatatnhde absence of S9 activation. In Vitro Mammalian Chromosome Aberration Test ~The purpose of this study is to evaluate the clastogenic potential ofa test substance based upon its ability to induce chromosome aberrations in human peripheral blood lymphocytes (HPBL). Telomer Research Program Feb. 2001 "Company Sanitized. Does Not Contain TSCA CBI" 14 $5 | TRP Toxicology and Descriptive Biology Studies Rat Bone Marrow Erythrocyte Micronucleus Test ~The purpose of this study is to evaluate the clastogenic | potential of the test substance as measured by its ability to induce micronucleated polychromatic erythrocytes in rat bone marrow. The micronucleus test is also able to detect chemicals that induce whole chromosome loss (aneuploidy) in the absence of clastogenic activity. Telos Sosesh Program Fo 200 "Company Sanitized. Does Not Contain TSCA CBI" 15 1% | TRP Pharmacokinetics Studies : Timeline CBI Information has been redacted Tetomer Research Program Feb, 2001 "Company Sanitized. Does Not Contain TSCA CBI" 16 17 TRP Pharmacokinetics Study | In Vitro Microsomal Metabolism Study ~The objective of this study type 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 Telomer Research Program Feb, 2001 "Company Sanitized. Docs Not Contain TSCA CBI" 1" 8 TRP Pharmacokinetics Study + Toxicokinetics of Telomer 8-2 Alcohol in the Rat ~The objectives of this study are to determine the Absorption, Distribution, Metabolism and Excretion (ADME) of Telomer 8-2 Alcohol in male and female rats following oral and dermal dosing. Telomer Research Program Feb, 2001 "Company Sanitized. Does Not Contain TSCA CBI" 18 19 Radiolabeled 8-2 Telomer B Alcohol F(CF,), "CF, -CH,CH,-OH Neededfor Pharmacokinetics & Environmental Fate Studies CBI Information has been redacted Telomer Reseach Program Feb 2001 "Company Sanitized. Does Not Contain TSCA CBI" 19 20 Radiolabeled 8-2 Telomer B Alcohol : Synthesis Route "A" CBI Information has been redacted Tetomer Research rogram Fe. 2001 "Company Sanitized. Does Not Contain TSCA CBI" 20 al CF5 "CF, -CH,CH,-OH : Timeline CBI Information has been redacted SmI "Company Sanitized. Does Not Contain TSCA CBI" 2 22 TRP Environmental Fate & Effects Studies * Focus on: -- Physical - Chemical Properties -- Environmental Fate -- Environmental Effects -- Bioconcentration ott Rotor Brg 0 "Company Sanitized. Does Not Contain TSCA CBI" 2 a3 Physical - Chemical Properties | n-CgF,CH,CH,0H * Molecular Weight | + Boiling, Melting Point * Vapor Pressure Water Solubility CBI Information has been redacted * Log K,, (Octanol - Water Partition) * UV/ Visible Absorption Spectrum * Henry's Law Constant + Adsorption/desorption onto glassware Telomer Research Program Feb. 2001 "Company Sanitized. Does Not Contain TSCA CBI" 23 ay Environmental Fate & Effects Work Plan Environmental Fate : Abiotic Physical Properties + Adsorption / Desorption + Indirect Photolysis in Air UV/Visible Spectrum Water Solubility + Adsorption to Glass Environmental Fat:e Biotic + Anaerobic Biodegradation* CAoierf-fWiactieerntPartition * A(e*rRoadbiiolcabBeileoddMeagtreraidalation* | Telomer Research Progam Feb 2001 Environmental Effects + Bioconcentration Factor + 90 Day Early Life Stage Study -- Rainbow Trout + 21 Day Invertebrate Daphnia Study "Company Sanitized. Does Not Contain TSCA CBI" u $ Physical - Chemical Properties : Vapor Pressure n-C4F,,CH,CH,0H Experimental Vapor Pressure Data i for CBF17CH2CH20H 160 ---- T 100 f---- ~ 120 100 (psiJa))60 | 1 1 b_ d| 0p 20 --1 00 400 60 -- 1 | meted 80 1000 1200 1400 1600 1800 2000 2200 T(C) "Telomer Research Program Feb, 2001 "Company Sanitized. Does Not Contain TSCA CBI" 25 a6 Environmental Compartments | CBI Information has been redacted Based on Emissions, Applications/Uses, and Physical-Chemical Property Information : ~ Water and Soil are the major compartments Airis a minor compartment Toomer Research Program Feb, 2001 "Company Sanitized. Does Not Contain TSCA CBI" 27 2% | Routes to E-Fate Goal: Identify environmental transformations relevant to toxicity and chemical cycling E-Fate (laboratory) Abiotic Biotic Telomer Research Program Feb. 2001 "Company Sanitized. Does Not Contain TSCA CBI" 2 28 Vv Adsorption fy E-Fate: ABIOTIC gv m Absorption Er | Hydrolysis y Yes || No Volaie 1] [ I EE ED | iid fr nai fri Yes | in Water pr No ve a Reactions Identity Products Evaluate necd for fur~ther testing Telomer Research Program Feb. 201 "Company Sanitized. Does Not Contain TSCA CBI 2% 21 E-Fate: Abiotic Degradation Studies * Hydrolysis | -- Transformation of a test chemical by reaction with water into new chemicals * Adsorption/Desorption Studies -- Evaluate the migratory tendency of a test chemical into the air, water, and soil or sediment compartments of the environment | Indirect Photolysis -- Assess the reaction of a test chemical that is a result of chemical or electronic excitation transfer in air Telomer Rescarch Program Feb, 2001 "Company Sanitized. Does Not Contain TSCA CBI" 30 29 | Hydrolysis Objective: To assess hydrolysis, which represents the transformation ofa chemical by reaction with water into new chemicals. Methods: *OPPTS 835.2130/0ECD 111 Test substance concentration is less than one-hailtfs water- solubility and not greater than 10 M * Sterile glassware and aseptic conditions used in the preparation of all solutions and in performing experiments pH3,7,and 11 Temp. 20, 40, and 60C + Minimum of7 time points Results: - Rateofhydrolysis as a function of pH at a fixed temperature - Rate of hydrolysis as a function of pH and temperature - Rate of hydrolysis and the chemical half-life in the environment Telomer Research Program Feb 201 "Company Sanitized. Does Not Contain TSCA CBI" 3! | 0 E-Fate: Hydrolysis LITT ENE JRE 2X fr Tre | PH 3,7, B 11at20, 40, 60C > 6 time points, 5 between 20 and 70% hydrolysis 70 to 80% hydrolysis within 1 week >10% Hydrolysis within 5 days Yes No Identify Products No Additional Testing Required Rl Hydrolytically Stable Telomer Research Program Feb. 2001 Determine need for further testing *Comnpany Santizdd DEE seNOT COREE TS BI | 3| Adsorption/Desorption Studies | Objective: To evaluate the migratory tendency of chemicals into the air, water, and soil or sediment compartments of the environment. Method: "*FOoPuPrTiSnit8ia3l5c.o1n2ce2n0t/r0atEiCoDns1u0p6 toone-half saturation but <5 mg/L + Minimumofnine adsorbants; 3 soils,3 sediments, 3 sludges + Up to 4 time points * 3 adsorbant/solution ratios | Results: - Mass Balance -- APdesrocrepnttiaodns/odrepstoiropnt/idoensoKripnteitoincs - Adsorption/desorption Isotherms Telomer Research Program Fe 2001 "Company Sanitized. Does Not Contain TSCA CBI" 33 2| Indirect Photolysis in Air | Objective: Assess the atmospheric degradation of n-CgF,,CH,CH,OH | by hydroxyl radical in air. Method: + * * + Pulsed laser photolysis of H,0, Analysis of product(s) by FTIR, GC-MS Absence and presence of NO, follow protocol described in cited reference Results: + Indirect photolysis rate constants Half-life of test chemical in air + Major oxidation product(s) as well as their reactivity | Reference : Atmospheric Study of C,FCH=CH, and CgF,CH=CH,, J.Phys. Chem. 2000 104, 8512-8520. Sr RB "Company Sanitized. Does Not Contain TSCA CBI" ay 3| | E-Fate: Biotic* | Anaerobic Aerobi:c || Methanogenic Sulfate . Reducing o No Segradatii on? Yes Test otherr Test other hi habitats? | | 1.D. Products Evaluate need for further testin9) [+ Radiolabeled Material Evaluar neec further testing olor Rss eg Feb 2000 "Company Sanitized. Does Not Contain TSCA CBI" 3 35 Environmental Fate - Biotic Studies + Aerobic Aquatic Biodegradation - The purpose of this | test is to examine biochemical transformation by aerobic (+0,) microbes from exposed and unexposed habitats and to determine the decomposition kinetics and fate of the chemical of interest. * Anaerobic Biodegradation - The purpose of this test is | to examine biochemical transformation by anaerobic (-O,) microbes from exposed and unexposed habitats and to determine the decomposition kinetics and fate of the chemical of interest. "Telomer Rescarch Program Feb, 2001 "Company Sanitized. Does Not Contain TSCA CBI" 35 36 Aerobic Aquatic Biodegradation Objective: Determine biodegradation potential for Telomer BA 8_2 under aerobic conditions in aerobic sludge matrix. Methods: + Aerobic incubation of microbial communities from an exposed and unexposed habitat (based on OPPTS 835.3170 & .3100 with extended incubation) + Microbial toxicity screen to determine high and low dose levels + Follow parent/product transformations for up to a 1 year period + Parameters - parent compound concentration, product identification, total heterotrophic microbial count, alcohol metabolic monitoring Results: + No observable adverse effect level for heterotrophic microbes + Kinetics of aerobic decomposition + Product identification eRe "Company Sanitized. Does Not Contain TSCA CBI" 3 37 Anaerobic Biodegradation | Objective: Determine biodegradation potential for Telomer BA 8_2 under anaerobic conditions in a saturated, landfilled sludge system | Methods: + Anaerobic incubation of microbial communities from an exposed and unexposed habitat (based on OPPTS 835.5154) + Microbial toxicity screen to determine high and low dose levels * Follow parent/product transformations for up to 64 weeks under both sulfate reducing and methanogenic conditions + Parameters - parent compound concentration, product identification, total counts: heterotrophs, sulfate reducers, & methanogens, alcohol metabolic monitoring Results: * Kinetics of anaerobic decomposition * Product identification + No observable adverse effect level for anaerobic microbes elomer Rescarch Program Feb. 2001 "Company Sanitized. Does Not Contain TSCA CBI" 3% | 3| Environmental Effects Studies * Acute Toxicity Tests - The purpose of these tests is to | determine the chemical concentration that effects (EC50) or is lethal (LC50) to 50% of the test organisms; the endpoints assess immediate, short-term adverse effects, e.g. immobility, survival. * Aquatic Chronic Toxicity Tests - The purpose of | these tests is to determine the chemical concentration that causes long-term, chronic effects on the test organism (survival, growth, reproduction). Telomer Research Program Feb, 2001 "Company Sanitized. Does Not Contain TSCA CBI" 39 38 | Aquatic Chronic Toxicity Studies | Objective: The purpose of these tests is to determine the chemical concentrations that are associated with long-term, chronic effects (NOEC, LOEC) on survival, growth, and reproduction of an aquatic invertebrate (e.g., Daphnia) and a fish (e.g., rainbow trout). Methods: e.g. USEPA OPP 72-4; USEPA OTS 797.1000, 1330; ! OPPTS 850.1300, 1400; OECD TG 210, 211 + Includes acute limit test Dose response, analytical confirmation of test concentrations + indications of cumulative or reproductive effects dose response, analytical confirmation of test concentrations Results: assess effects on survival, growth (length, weight), reproduction Totornes Rossa Progam Ft 201 "Company Sanitized. Does Not Contain TSCA CBI" 39 yo Aquatic Bioconcentration Study Objective: To determine the bioconcentration potential of a chemical (uptake and depuration potential), focus may be ecological and/or human health Methods: e.g. USEPA OPP 72-6; USEPA OTS 797.1520 OPPTS 850.1730; OECD TG 305 + uptake (steady state) and depuration phases + analytical confirmation of test concentrations and tissue | residues | Results: | + BCF, uptake and depuration coefficients i Tots Smee Eran Eh "Company Sanitized. Does Not Contain TSCA CBI" "0 2] TRP Environmental Fate & Effects Studies : Timeline | CBI Information has been redacted Toomer Reseach Program Feb, 2000 "Company Sanitized. Does Not Contain TSCA CBI" a yr TRP Database + Product Categories -- Intermediates -- Surfactants -- Polymers * Information Types -- Toxicology -- Environmental Fate & Effects * Discussion & Analysis - March 2001 Tetorsos Rossa Srogam Fe, 200 "Company Sanitized. Does Not Contain TSCA CBI" "3 | | 2| TRP Path Forward Items Toxicology & Descriptive Biology Pharmacokinetics + Radiolabel Environmental Fate * Environmental Effects * TRP Database * Analytical + Summary Toto Ssosants Frogger Feb 20 "Company Sanitized. Does oNot Contain TSCA CBI" | | 5|