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DuPont Chtmical Solutojuo Entirp P.O.Box 80023 Wilmington. DE 19880-0023
DuPont Chemical Solutions Enterprise
September 24, 2001
Karen Lannon U.S. EPA, OPPTS Document Control Center 4 0 1M Street, S.W. (TS-7407) Washington, DC 20460
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Reference: AR266
Dear Ms. Lannon:
I have once again prepared authentic sanitized copies o f the two presentations we gave on February 21, 2001. A paper copy o f each 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 o f these reports has been company sanitized. They do not contain TSCA CBI. Each and every chart that has had CBI removed has been marked with the following note: "CBI Information has been redacted."
Please let me know if you have any additional questions on these two documents. You
can reach me via phone on (302)992-3672 or fax on (302)892-1135. My email address is
stephen.h.korzeniowski@usa.dupont.com.
g
With regards,
c
Stephen H. Korzeniowski Market & Business Manager
SHK/klo
Attachment
Company Sanitized
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Company Sanitized
Telomer Research Program Update and Status Report
Presented to U.S. EPA, OPPT 21 February, 2001
Telomer Research Program Feb. 2001
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TRP Member Companies
Asahi Glass Atofina Clariant Daikin DuPont
Telomer Research Program Feb. 2001
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Agenda
TRP Toxicology & Descriptive Biology Pharmacokinetics Radiolabel Environmental Fate Environmental Effects TRP Database Summary
Telomer Research Program Feb. 2001
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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 Meeting
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TRP Review with U.S. EPA : 23 Oct. 2000
TRP Members, Principles, Structure, Processes Chemical to be tested : n-C8F17CH2CH2OH
- Toxicology and Descriptive Biology Studies : Protocol Review - Pharmacokinetics Studies : Protocol Review - Radiolabel Work - Environmental Fate Outline - Overall Timeline
Path Forward Items
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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 even if phased in. Want to review program when methods are complete. Feb 2001 target.
Telomer Research Program Feb. 2001
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TRP Chemical to be Tested
Telomer 8-2 Alcohol: n-C8F17CH2CH2OH
Purity >99%, and characterized Sample made, 20 kg
Telomer Research Program Feb. 2001
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n-C8F17CH2CH2OH Analysis Profile
Purity > 99% by G.C.
- 99.2% n-C8F17CH2CH2OH - no other CnF2n+1CH2CH2OH species - 0.8% impurity
CBI Information has been redacted
Telomer Research Program Feb. 2001
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TRP Toxicology and Descriptive Biology Studies : Timeline
CBI Information has been redacted
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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
Telomer Research Program Feb. 2001
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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
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TRP Toxicology and Descriptive Biology Studies
Developmental Toxicity Study in Rats
-The purpose of this study is to evaluate the developmental toxicity of Telomer 8-2 alcohol, administered by gavage, to pregnant rats from the time of implantation to the end of gestation.
Telomer Research Program Feb. 2001
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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 Feb. 2001
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TRP Toxicology and Descriptive Biology Studies
Bacterial Reverse Mutation Test with an Independent Repeat Assay
-The purpose of this study is to evaluate the mutagenic potential of the test substance by measuring its ability to induce reverse mutations at selected loci of several strains of Salmonella typhimurium and at the tryptophan locus of Escherichia coli WP2 uvrA in the presence and absence of S9 activation.
In Vitro Mammalian Chromosome Aberration Test
-The purpose of this study is to evaluate the clastogenic potential of a test substance based upon its ability to induce chromosome aberrations in human peripheral blood lymphocytes (HPBL).
Telomer Research Program Feb. 2001
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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.
Telomer Research Program Feb. 2001
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TRP Pharmacokinetics Studies : Timeline
CBI Information has been redacted
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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
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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
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Radiolabeled 8-2 Telomer B Alcohol
F(CF2)7 14c f 2-c h 2c h 2-o h
Needed for Pharmacokinetics & Environmental Fate Studies
CBI Information has been redacted
Telomer Research Program Feb. 2001
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Radiolabeled 8-2 Telomer B Alcohol : Synthesis Route "A" CBI Information has been redacted
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C7F1514CF2-CH2CH2-OH : fime^ne
CBI Information has been redacted
Telomer Research Program Feb. 2001
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TRP Environmental Fate & Effects Studies
Focus o n :
- Physical - Chemical Properties - Environmental Fate - Environmental Effects - Bioconcentration
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Physical - Chemical Properties
n-C8F 17CH2CH2OH
Molecular Weight
Boiling, Melting Point
Vapor Pressure
CBI Information has been
Water Solubility
redacted
Log Kow (Octanol - Water Partition)
UV / Visible Absorption Spectrum
Henry's Law Constant
Adsorption/desorption onto glassware
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Environmental Fate & Effects Work Plan
Physical Properties UV/Visible Spectrum Water Solubility Adsorption to Glass Air-Water Partition
Coefficient
Environmental Fate : Abiotic Hydrolysis Adsorption / Desorption Indirect Photolysis in Air
Environmental F a te : Biotic
< Anaerobic Biodegradation* Aerobic Biodegradation* (* Radiolabeled Material)
Telomer Research Program Feb. 2001
Environmental Effects Bioconcentration Factor 90 Day Early Life Stage Study Rainbow Trout 21 Day Invertebrate Daphnia Study
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Physical - Chemical Properties : Vapor Pressure n-C8F 17CH2CH2OH
Experimental Vapor Pressure Data for C8F17CH2CH20H
p
(psia)
Telomer Research Program Feb. 2001
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Environmental Compartments
CBI Information has been redacted
Based on Emissions, Applications/Uses, and Physical-Chemical
Property Information :
- Water and Soil are the major compartments
- Air is a minor compartment
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Routes to E-Fate
Goal:
Identify environmental transformations relevant to toxicity and chemical cycling
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Telomer Research Program Feb. 2001
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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
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Hydrolysis
Objective: To assess hydrolysis, which represents the transformation of a chemical by reaction with water into new chemicals.
Methods: OPPTS 835.2130/OECD 111 Test substance concentration is less than one-half its watersolubility and not greater than 10"3M Sterile glassware and aseptic conditions used in the preparation of all solutions and in performing experiments pH 3, 7, and 11 Temp. 20, 40, and 60C Minimum of 7 time points
Results: - Rate of hydrolysis 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
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Preliminary Stud pH 3, 7,11 60C
Hydrolysis of Unstable Substances pH 3, 7, 11 at 20, 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
No Additional Testina Reauired
t1/2> 1 year Hydrolytically Stable
Telomer Research Program Feb. 2001
Determine need for further testing
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Adsorption/Desorption Studies
Objective: To evaluate the migratory tendency of chemicals into the air, water, and soil or sediment compartments of the environment.
Method: OPPTS 835.1220/OECD 106 Four initial concentrations up to one-half saturation but <5 mg/L Minimum of nine adsorbants; 3 soils, 3 sediments, 3 sludges Up to 4 time points 3 adsorbant/solution ratios
Results: - Mass Balance - Percent adsorption/desorption - Adsorption/desorption Kinetics - Adsorption/desorption Isotherms
Telomer Research Program Feb. 2001
"Company Sanitized. Does Not Contain TSCA CBI"
Indirect Photolysis in Air Objective: Assess the atmospheric degradation of n-C8F17CH2CH2OH by hydroxyl radical in air. Method:
Pulsed laser photolysis of H20 2 Analysis of product(s) by FTIR, GC-MS Absence and presence of NOx follow protocol described in cited reference Results: MIHnadalijfro-elricfoetxpoidhfaotettiosoltnycsphisreomrdauitcecatcl(soin)nasastiarwntesll as their reactivity
Reference : Atmospheric Study of C4F9CH=CH2 and C6F13CH=CH2, J.Phys. Chem. 2000 104. 8512-8520.
Telomer Research Program Feb. 2001
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Telomer Research Program Feb. 2001
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Environmental Fate - Biotic Studies
Aerobic Aquatic Biodegradation - The purpose of this test is to examine biochemical transformation by aerobic (+02) microbes from exposed and unexposed habitats and to determine the decomposition kinetics and fate of the chemical of interest. to AenxaamerinoebibcioBcihoedmegicraaldtraatniosnfo-rmThaetiopnurbpyoasneaoefrtohbisicte(-s0t 2i)s microbes from exposed and unexposed habitats and to determine the decomposition kinetics and fate of the chemical of interest.
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Aerobic Aquatic Biodegradation ObjeDcetitveaerem: roinbeicbcioodnedgitriaodnastiionnaeprootebnictiasllufdogrTeemloamtriexr. BA 8_2 under Methods:
Aerobic incubation of microbial communities from an exposed and euxnteexnpdoesdedinchuabbaittaiot n(b)ased on OPPTS 835.3170 & .3100 with
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 KPirnoedtuiccst iodfeanetirfoicbaitciodnecomposition
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Anaerobic Biodegradation
ObjeDcetitveaernm: aienerobbiicodceognrdaidtiaotniosninpaotseanttuiarlaftoerd,TelalonmdfiellredBAslu8d_g2eusnydsetrem
Methods:
MAPFtismnuoacounlarrtleaoolaeeftmabwlaxroitcpbaeepbooolteaiurslctieorrncesedixtdnsnmui-cc:thc/ouiptphianynbarebgiarotsteioettdcaianrorurintotenncdt(cegtrbooontmarmfpastmehoepntsdohisdc,fuareoosonntrunebdomlrfigOaamcaeltoPteinicnonPioecrncTemeschSdnmoifugto8nrchuar3dentu5airitiospti.noi5n,edtn1,&sos5lpof64mrrwoo4)emddwtuhoeacasetnnekiodeslgeexeuvnpnentoislfdssi,ceeaardtlbcioaoonnthhd,ol
Results: Kinetics of anaerobic decomposition Product identification No observable adverse effect level for anaerobic microbes
Telomer Research Program Feb. 2001
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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
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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
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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
Telomer Research Program Feb. 2001
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TRP Environmental Fate & Effects Studies : Timeline
CBI Information has been redacted
Telomer Research Program Feb. 2001
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TRP Database
Product Categories
- Intermediates - Surfactants - Polymers
Information Types
- Toxicology - Environmental Fate & Effects
Discussion & Analysis - March 2001
Telomer Research Program Feb. 2001
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TRP Path Forward Items
Toxicology & Descriptive Biology Pharmacokinetics Radiolabel Environmental Fate Environmental Effects TRP Database Analytical Summary
Next TRP Meeting : 20-22 March 2001
Telomer Research Program Feb. 2001
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