Document jyMEBE40kZNO3m2w5yMK7yK02
3500
(TR 52k |
AR 226 _ (042
DuPont Product Stewardship Update
United States Environmental Protection
Agency
17December 2001
R. C. Buck, G. L. Kennedy,S. H. KorzeniowskJ.iC,. Stadler
cme se TE
P88eg3oi8n) 5z 2&5
|e
Discussion Outline
+ Reconnect to 21 Feb Discussion
++ TWooxrikcoPlloagnys & Chemistry, Radio-label ~~ BRieoppeeartseidstDnocsee,, Reproduction & Developmental Studies ~ Structur-e Activity Relationships
+ E=xHpuosmuarneECxpoonsnuerceti:Woonr:keWrhDaatt,thCeodnastuamemreans.
~ Environmental Exposure.
S 2
+ Environmental Fate & Effects
~~ P Envih rony m-enCts haelmii FcaatelcProa pertl ies ~ Environmental Effects + Conclusions.
2a 22 39
=- = Ba 2 25
+ Discussion
GE Chomtotues Error TAG
:
3
Company Sanitized
1
1
Caltomasasontaccoion
.
EL --
,
temediaDotumPsaondtaFteusrSuotarcarPrso,dSuPcatooGsrmoPuerpst:cs ann
r:er Cm_)-, |
StaciAa a "Moles" re tes
F(CF,CF;),CH,CH,1 (TelomBer)
|
9 pamarsCBI Information has been redacted
[ FCF,CF;),CHCHON (TelomerB4) reraracncnocommcn, |
-8i LLd5oEn3ede
[------
hmsns ER
.
2
Synthetic Strategies for
Radiolabeled Fluorotelomers
FF CF OH
FF [3 PN
November 2001 DCSE R&D
SB:Crm Emre REG
:
General Synthetic Strategy
FRN F
or -->ooBe > oBrFd _ }
CX
CF
~~ F GFoH
"TF-Eprnacotticaal svyassmositodeureacemsoobfrtiadelioSlHaebEelsus + M~ust8.us.eCOr,ea(dexi.lByaaCvOa,i)l,abNleeCNso,urtccesof"C
~~ apimalpreeagrentes: pEreSceFd,ent(foDAcSoTn)ve(rsMiOonCoHfC,C=HO,,nNtSFC,F,(DeoxoFlort)
TE: emtsonspers AG
`
3
Radio-label Synthetic Routes
+ Multiple (5+) Deoxyfluorination routes explored using different starting synthons
GBI Information has been redacted
.
Com Sn corn
,
Successful Synthetic Route
CBI Infomation nasbeen redacted
+ STyemlbohmeercAR,ouTteeloprrcoevidBaesndaccTeeslom0easlBtAhe eyFlucrotelame Inermedises
cosa a, CTL Scr
.
4
ProductStewardshipAnalysis
IT
posurefoaw How much
JOfoPes
De itdc
`What?
ED
itgo
#
p
Risk = f (Exposure, Hazard)
EXChemieSoonEner
REG
&
Toxicity Studies | ABseald,i
| RIenOphhaellaaDtteiDornoma(slAeETLo)iciey
Basic evaluationset
DevelopmentalToxicity Reproductive Toxic
Pharmacokinetics
-
pa Ee
0
5
Summary :inOrVgiavnoiBcloCpheermsiicsatlesncne SMcarleeeRnaitnsg of Fiuoro-
+ Pseurripesosofe:fuTooroctolmopmaerre ibnitoe-rumpetdaikaetea,nsdurbfiaoc-tcalnetaraanndcepoilnyrmaetrbilcood for a. products inclding PFOS as apie control.
+ Spetruidod:yw1i0thcoannsaelcyustiisovefwdaayls Bdolsoiondg,vLiiaovrea&lrgFaavaMgue8o4,ndaoyn rseecleocvteerdy
days (3 during dosing, 4during recovery).
+ dornganaic:matUesriealRsuoornineddoastntoorcmoamlpiazredeoirntmeomlalarexbpaossius.re offluoro
Bl normaton has been redacted
wm
corms strc
fl
CBI nformaton hasbeen redacted
0: Comic nts Evens SERGE
"
6
(CBI Information has been redacted
|OW: homiEeners ComSapReGsotConin
n
G8 Information has been redacted
I:ChacesoinsEvie CompanySten.aSse otorn
" 7
GBI Information has been redacted
I rome von Erie
Rage
*
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 lowerthanPFOS
GBI Information has boen redacted
pe.
ene CSen
"
8
Repeated-Dose Study Plans
90 Day Subchronic Stud Determine systemic effectsfrom repeoraa tgaevadge exposure One-Generation Reproduction Stud Determine effects on parental capability to concbeaerofifspvrinega,nd evaefflectusonaofftspreing during pregnancy, cary feeanddmaiturnatigon 1 adulthood Dexelopmental Toxicity Stud Determineeffects on fetal development (Lc. growth,marion,somali)
an
one CSin
w
90 Day Repeated Oral Dosing & One-Generation Reproduction Study
Dae Levels Experimental Animal
three levels + control Ma &Feml alee CD Rats
Study Exaluations
9R0DeaypeatDeosde : * UapSpeaErPaAncHeo,sbkehhaEvfioer, TweesitghGtu,idbelloionde, oOPr PTSag8n7d0at3i1n s0su0s es(1,9f98-)oxidation
R+ eAprdoudIunlcfttei:o:nbody wt. clinical sigs, limited histopathology, female
reerprloydu;ctive cycletime, sperm asessmen, reproductive organs, mating,
+ Pups: physical develaondpmmatuerantiotntoadulthood,reproductive organs
0:Comtestnerrr p----R--E------
"
9
90-day & One-Generation Reproduction Study Protocol =
ii
i1
weTeoT c ual} soR anomorues EFrere
Roend=TORR rere
Rvaepse romMI
= 1hau--sr prs
ieoy. re
oy coy 2 " zr
bs
ios Fuori -- 1
jeans
1i 858 FF EEE; yy os 3
-
i Company Sst fo otCon rin
"
Developmental Study
DoseLevels:
"ThreeDo+sCeontsrol
Experimental dnimal: Male& Female CD Rats
USS. EPA Test Guidelines : 870.3700; OECD Sect. 4, No. 414
StudyEvaluations Determine effects on fetal development (Le. growth, maturation, sbnomaltes)
Matcmal: clinical signs, body weight, gross pathology Bugssex,bodyweight, extemal, skealnedvitscaerlal examinations
=
Como eneeoni
10
DuPont Toxicology Studies Timeline
BI Information as been redacted
on
Com Stnetecoin
u
Telomer BA Synthesis Chemistry
CReCF, (FE)
wo (Telomer A) [n=3-6]
F(CF,CF),CH,CH,l (TelomeBr)
F(CF,CF),CH,CH,0H _TelomerBA Staight Chain Aly!
|OB hamictStsons mie RACH
2
1m
Actual Telomer BA Study Material Composition
-
+
or 2
J
F(CFLGF.,CH,CH,0 Chai Longthn= Number
CE ChamaStnsEmre AG
3
Telomer BA : Repeated-Dose Toxicology Information F(CF,CF,),CH,CH,0H a=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
SEB: Chom Stns Emre
TEA
ty
n
Telomer BA : 90 Day Study Results
StudyConclusion: NOEL= 25 mg/kg/day
em ----;
=.
mg
.
One-Generation Reproduction Study : F1 Survival Indices
$7d7
Lf/
= =o EE
aro heree
SB ChemictSotutons Emrive
TAC
13
Telomer BA : Reproduction Study Results StudyConclusion: NOEL = 25 mg/kg/day
[ET ----
a: cosa
En
Telomer BA : Developmental Study Results StudyConclusion: NOEL =200 mg/kg/day
Bl normaton has been redacted
I: Cromersoos Emr TAG
*
14
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
ome
CS cn
Telomer Ethoxylate : Chemistry
F(CF,CF),CH,CH,0H
wo
BI Information as been redacted
F(CF,CFy),CH,CH,0(CH,CH,0)H,
+ ProbdyPuroccests.
+ MisoftMixuturees: Fluorocasbon Chain nd EO Chaareibonth gaussian disrbutons nd ailfoorspeecidfic nd-uses
p
Com Snomc
15
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
0: ccmiotsututons pre
TRG
u
Telomer Ethoxylate : 90 Day Study Results StudyConclusion: NOE=L 25 mg/kg/day
Bl Inormaion hasbeen redacted
va
[--
16
Telomer Ethoxylate:Reproduction Study Results `StudyConclusion: P, NOEL = Not Established
F, NOEL = 25 mg/kg/day
GBI Information has been redacted
0: comes ems ERG
>
One-Generation Reproduction Study - P1
Fertility Index (%) = # Animals that Deliver Pups # Animals that Mate
+ Fertility Index accounts for any event from matingto birth.
+ Reduction may be due to lack of fertilization, implantation or embryo viability
=
TT
"
17
Telomer Ethoxylate : Developmental Study Results `StudyConclusion : NOEL 50 mg/kg/day
GBI Information has been redacted
I Cromree ERG
*
Telomer Ethoxylate : Study Conclusions
+ Subchronic ~ Primary adverse targets are redblood cell mass & kidney ~ Other compound-related effects were non-adverse physiological responses: liver, thyroid, spleen
* Reproduction -- pefufpect(sFIo)nebffleocotds aocncdukrirdendeyonly at dose levels with systemic 08 Information has been redacted
+ Developmental ~ not a selective developmental toxin
--y
. CorrSgnmeon
*
18
BI Information has been redacted
pe.
pre CS rn
Telomer Phosphate Chemistry
F(CF,CF,),CH,CH,OH
|
GBI Information has been redacied
[F(CF.CF,),CH,CH,0] P(OXONR iH),
+ Products by Process + BL,B Telomer Distributions tailored to end-use
a
a CSSenn
19
Telomer Phosphate : Study Update
+ 90 Day Repeated Dose Oral Gavage Study ~ production material ~ In-life complete, histopathology evaluations ongoing
+ Reproduction & Developmental
~range finder underway ~ studiesto begin 1Q2002
CBI information has been redacted
>
pra CO Cn
Telomer Urethane Polymer : Chemistry
HCFCRACHCHON (Tomar) ----. Loner Urethane
BI Information has been redacted
oo
a Co rn
20
Telomer Urethane Polymer : Repeated Dose Toxicology Information
+ Repeated Dose Toxicity: + Reproductive Toxicity:
LOEL S0mg/kg/day (nose only) No ObservedAdvereEffectat 0 mg/day for all therpares No effects on reproduction at any dose level
+ Developmental Toxicity: No abnormalities or birth defects
+ Genetic Toxicity:
Negative AMES and Chom Ab
an
ra, Cove cnn
"
Telomer Urethane Polymer: 90 Day Study Results Study Conclusions NNoOEOLbseNrovteEdsAtadbvleirssheedEffect atS0 mk day for alotherparameters
BI Information has been redacted
Pp.
Combs res Corin
a 21
Telomer Urethane Polymer: Reproduction Study Results
StudyConclusion: NOEL = 50 mg/kg/day No effects on functional reproductive parameters at any dose level
Gal formation has been redacted
SO: Cami teins Evie TAG
Telomer Urethane Polymer: Developmental Study Results
St~ uDdevyeCloonpcmleunstialonNs:OEL = 250 mgrkg/day + Maternal NOEL = 50 mykg/day
Bl normaton hasbeen redacted
=
Comp setgrtan
"
2
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
~ nota selective developmental toxin
-
Corp enesein
=
GBI Information has been redacted
Po
Cony tnGeson
" 2
Fluorotelomers Exposure Assessment
In-Use Exposure Assessment Environmental Release Assessment
~ Product Trails + extemal focus : markets where used + distribution, use, disposal
~ Mass Balance
+ Environmental releases & media (Land. Air, Water)
-
par, CoS rec
a
: In-Use Exposure Model
GBI Information has boen redacted
a cme
Com tnd Geron
2
: In-Use Exposure Model BI Information has been redacted
pe.
Com St etGrn
o
: In-Use Exposure Model
BI Information has been redacted
oo
Com Snecon
25
Product Trails
+ For each Marke/t End-Use by Product + Usedtodetermine product release points
ProTrdailu :Cacrptet
=-- 1
--
oom | CHR sa oS, = Disposal
=
| Rosdental |
>
Come Stn ocr
"
BI Information has been redacted
"
a CS ene
=
26
Enviro`bnasmedeonntemailssiConosamssposasrmotntments GBI Information has been redacted
TE: ho tosEi mre TAG
2
DuPont Environmental Fate & Effects Studies
GBI Information hasbeen redacted
EE] [LT
Environmental [0
Environmental 20
_--
Company Sot,Gos otCan
Pl
27
Study Materials
GBI Information has been redacted
0:Comeetmesr REG
Physical - Chemical Properties
-C4F,;CH,CHpX, n-CgFiCH,CHX X= OH. |
+ UV/ Visible Absorption Spectrum + Vapor Pressure + Sorption + Water Solubility + Henry's Law Constant
+ LogK,, (Oc-tWataerPnartoitilon)
SO homens etn rss
REA
28
UV-Visible Spectra: Telomer B Alcohols & lodides.
+ No absorbanicne visible light range, 350-800nm,
+ Direct photolytic degradation not expected
Indirect Photolyss [OH Radical]workunderway (8-2 Alcohol, TRP)
CB:ChomastunsEvers CompanySiHnseGerorGorn
o
Vapor Pressure :Telomer B Alcohols & lodides
Temperature (0)
+ Data fit to Antoine Equation extrapolated 0 ambient, 20C + No anomalies observed
>.
ConorSe eeson
=
29
Physical - Chemical Properties : Sorption 6-2, 8-2 Telomer B Alcohols & lodides
+ rapid sorption from saturated aqueous solution ~ glass, slnized los, plastic, PTFE, sinless tl
+ evidenceofime.dependent adsorption with decreasing abil 0 recover materialfrom surface(s)
+ specific recovery methods had tobe developed and validated ~ wks foreach simple resch equilibrium with continous analysis ~ $1020 samples episodto abi method and analysis confidence
+ makeswate solubility measurementmuchmorecomplicanadtmaesds
`balances difficult to achieve
ER Choi tinrie
AG
"
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 mateisradisoarbeld to the container, not in the water, when
excess material is no longer present
~ sorbed toth container surfaces
BI Information as been redacied
EB Chom tntre TRAG
30
Physical - Chemical Properties: Water Solubility
6-2, 8-2 Telomer B Alcohols & lodides
ze 25C rc [ee
rronron |CsF13CHzCH.OH
oFwir
[orzo] o:ous[onezo preliminary data 1 range
|
PrT roosa owwon [] |
- J . + De-ionized water measurements
Physical - Chemical Properties: Henry's Law Constant 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 tere TY to Measure utilizing Static Headspace Method
SO:Crm ionsEmrss
RAG
a
31
Phys6i-c2a,l8--C2hTeemliocmaelrPBroAplecrothioelss: &Colnocdliudseisons + Water Solubility varies wiTtbuht notpi an ithe rangeof0.1- LOppm.
Highly soptive ontomanysurfaces and ayremainhighly sorbed and difficult to remove + PreliVmPidanaadornoyt exhibit anomalies: + Novsible light absorbance
+ These propertiespresentsignifica method develoapndmanealnysits challenges gong forward and wil egure use of mdiolabeled matenal for morstudies than expected
0:Comets pre
ER
Analytical : Method Development Challenges
+ Head-Space Analysis Method
~ Parent and potential degradation product(s) + Extraction & Recovery Methods
~ Matics: Soil Sediment, Sludge, Labware Surfces, Water ~ Materials : Pe&Den gradat tion Products), including raciclbel
+ Analysis Methods (GC/MS, LC/MS/MS)
~ pare&n Degradation Products) in relevant mates ~ Radiolsbeled Materials (sop-low scinilaion counter)
SB: ChemictStuionsEmeriss Smgr
"
2
Environmental Fate& PhysicalProperties
+ UV/Visile Spectrum + Water Solubility + AdsorpttoGiloasns +CAoierf-fWiactieernPtartition
Effects Work Plan EnvironFmatee:nAbtioatilc + Hydrolysis + Adsor/Dpestoriptioonn* EnvironFmaeten:Btioatilc + Anaerobic Biodegradation + AeRrosbitcBiiodsegtierraiddaation
CBI Infohrasmbaoetnreidaoctned | Env+ iBrioocnomnecennttarlatEifofneScctresen
>.
CompanySavge oaCt on
"
DuPont Environmental Fate & Effects Timeline CBI Information hasbeen redacted
0:hmsinter RET
" 3
DuPont Product Stewardship Summary
+ We are committed to and staying in the business. + Weare 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
0: com soon min
TR
7
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
0: homessti mi" TAG
"
+H
+ Reflections & Discussion
+ Questions
+ Path Forward
mms TRE
-
of