Document RaMxZK6qOkVnDN521b0Y7Dp6n
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Ap6 1568
ATTACHMENT I
3
I
WSL WNC BZA DUPONT LEGAL ENT
cwomotresm
gi--naen
WINDELS MARX LANE& MITTENDORF. 118 156 WesT SOTE STREET Naw Yomm. N.Y. 10018 p-- fax: 2m 262-1218
Ws oo
JEwa
Wmuomocr
`Scptember 7, 2004
TSCA Confidential Business Information Ceater (7407M) UE1S2PS0.A1EECnaovsnitsrt-oiRtnumoteoinomtnaA1lv4Pe2rr8outeec,tNio.nWA.gency
`Washington, DC 20004-3302
Ladies and Gentlemen:
Toxic Substan`cWees rCoenptrreoslenAtcMtI(CTSSpCeAc)i,alwteyCshuebmmiictaolns,bInec.boaPfulorufsrucalntieotntSeacctoipoyno8f(a) orfetphoret dated FeAarueusgiuoisrntogo2w3ci,tta2hn03o0Mi4catoncdMiiddtu(enPPiFOoSA.n)pt.t.oAdAibsyDceDuprs.asrGbulimooelvosagtnincMiaalCnmoaosgnteiatoroofrftihoneugroUcfnliMivieentrtesrnietcyweooifvrekVdeerrasocneoaxppydooessfcctdrhiteboing 2 FemorandimonAugust23, 2004 duringanoverseastip. imports PFOAMpiutrecahiasisedanfrIotamliMaintceonmipiantnoytwhheiUcnhitmeadnuSftaatcetsu.res PFOA in Italy. Our elient favorable and oIunrgeclnieernatld,toheesinnoftokrmnaotwiotnhdateasncyebienfdoirnmtahtieoenncilnotsheedrerpeoprotrtianpdpiecaatresstaosbuebstantial trfoiosmkr.amkaHetotiwheoevnesirsu,btmhoieusrosniclloiyneoinntnfiosarpnmoartteiiocnnaawpuohtsiiicthoibontanashtriaossym.saObkoueurtctthlahiteenbdtieaotldeovrgmiiiscneaaslttimhooanntitatnhoder,eintnchgelrdoeesfseocrdrei,bdeedciindetdhe report.
16you have any questions, please call me at 212-237-1140.
vrtruly yours,
cEcES:mgHitoshi Insda, Esq. Takehiro Fujimure, Esq.
Ms. Marian Roach
Goasaaray
Edward E. Shea
<
7 EREro2t0G04l7avaE2a0 ml Costa DUPONT LEGAL ENV! SEUposnaa, aiti8anMoi vegodhSietcduai drcddofrolVseLLan ravsoivinorraoo Pa 6,ag5eC eiGa,n16E r.5s741DoVzEeRONA FARCBTISGE
DSipectetz.ione MITENTSpA
Trissizo (VI)
`Verona,23.08.2004
Report onthemeeting held opFriday 20*andSaturday 21" 2004 at the Innat
Montchanin Village (Wilmington, USA)with 3MandDuPont delegations.
1. Panicipants:
--JGoehwnyBOultseaeknioff 33MM,,ctlaixniiccaalloegpiisdtemiologist
--PLeatmeyrZGoilbleiles D3uMP,ooatc,ecxpeurtpinableitapliitdmhpeohtyansbioacliilssnm
-JohnGreen DuPont, statistician
~-GReorbailndLKeoennaerddy DuDupPoonntt,,teapxiidceomloigoilsotgist
~RobertRickard -Giovanni Costa
MDiutPeonnit,,oaxciccoluogpistahetalithpohynsiacialn
2 Background
On August I have been invited by G. Olsen (3M) to participate in this meeting,
organised jointlywithP.Gillies(DuPont),aimedatdiscussingtheresultsoftheanalysisof
thedatacollectadbymeatMiteni plantinTrissiw,concerningtheworkersofthePF. department.
1 ee
LASER 07 EMM DUPONT LEGRL ENT prog GlovamiCosta
SpEG oacpioacirtaaidnvMoMogdaSceiusddr doiolViLeLnars avovoonarroo PlRpgeT Ven
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workiAngsgritowuaps,beavneasgraereeddlaassteyeeaatiifnectohlelaabmobriattioofntwhietAhtPhMeEm-sAiPmFeOdaatdehvoaleutaotxioigctohloegdiacatls
relateDdetsoptihteetpehreisodmiaclall,nbuimolboegricoaflwmoornkietorrsiinngvooMflivtedea(icowmoprakreerdstoex3poMsaenddtoDPuFPOaAp.tworkers),
suchdaawere considered
withbumanphysiology, 0
very
such
hcealbpofru:loifnwuonrdkeresrtahansbedeningancyhepocskseidbrleeginutlesraycstiinoncoef197F9 ObAy
o3nMuawolrmkeedris,casloemxeamwionrakteirosns(,oinntveolgurnattaerdybbyassiesv)ehraalvebbleoeodnacuhdecukreidn.eoacncaalsyisoinsa.lIyn(t1h9e5c3,as1e95o6f,
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theenTdhoefrefhoirsey,etahre.statisticalcnalysisofMitenidatawas consideredveryusefulfrchecking
chwheectkhseorofrlnarogteargnryopurpe-scaltini3McalaanddveDrusPeoenfftepcatscsou,ldadndefdoertfesuttehde,rimnoorredederttaoibleetdtienrvaedsdtrigeastsitohnes
on
some specific biological So,inDecember2003
parameters. (afrdiscussion
snd
agreement
withMiteni
general
management
themeetingheldinFrankfurtanNovember 217) I eatG,Olsenthe firstdambase of the
biclogicelmonitoringofMiteniworkers (in anonymonsformat)and,inFebruary2004, on
occasionofthe SOTConfezerice heldinBaltimore,Ihad afirstmestingwiththemandother
3M andDuPontexperts (scemyreport dated 29.03.04 and abstract below) for a preliminary
analofythsediatsa.
neat, wedecided ofotegntethedatasetwithsome morespecificanalysis
concerning the lipids metabolism, thst collected during the periodical, annual blood check
carriedoutin Springthisyear. Consequenty,twomonths
ago
I seat.
Olsenand P.Gilles two
updated detasets
(sll
{n smonymous format), one concetrhbnioilognicgaldaaavailable since 1987ofllexposed
workersto PFOA, sadthesecondoneconcerningthelastblood amalysiscarriedoutia Spring
2004.
2
pTE tme SERS.2004% S:3M DUPONT LEGAL tRvITTS +" Prof. Giovanni Costa
Eatodrs dlModdiolLcaraes PU e neirgvdao,eg1h5Sr.9ds73&i1VVEecrRoOhnNA
cr.cSoruSnuensaask
wr -
3. Preliminary resultsofthestatisticalanalysis
hespay of theftdese ilasts17mydearasvsretlatioan toptohseiPbFleOAsmblaoold levoelfs
bnidolopgoimcaaelexppteorhsaemtedtewsros4r,kyeoercactsuor(e2fdi0n0di0on-ut2th0ea0n3y)dheisfeofnsdthoeantenwccosuelad bee dsutisctoicmaplalyriansgsocipatoesded
PFOA exposure.
he sisal
sulyss,
cavedoutby
Dupont expersain,confimedte
mesnsofappropriate satel programsbY gaverlsforalmostallthe 37 bleed
purnmetesconsidered: in paiular oosigificn ceswere dori 3 concerns
`haematology,proteinsmetabolism,smmunology,liver,kidneyaod prostatefunction.
nly someslightcfson lipids metabolismweredetaced, which deserve Sure
analysIinsfaaacdt,praopleigrhitnitnercprreeatsaetioofnst.otal cholasterlinworksexposeto PFOAwas bierved.
whichsloappescedtoshowa0fcressin trend ssocirad withthe highestblood PFOA
levpelis.nabtein1scheowsofhtetclomhpaorlissnofienxepxopsoesdeadnwdonrkoewress.Tpohsesdwisornkoefrsrenedethoefolbigehct
pid, uchasSygocsdes in pul, but he raionofNoxHDL.Cholesterol"seems
thatconcerned. Figure 1showsthe positive.corrbee twel entaotat lchi oleo sten rol andPFOA blood levels
in
the
last 4 years (when
total cholesterol
PFOA was measured): a
concentration seems $0 be
slight association between, PFOA
consoivesrttheeyenarts. Figur2e
blood
shows
level and
hesamotrendas congemns
"Non-HDL Cholesterol"
3
7
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woul noo
Table 1: Comparisonofthe mainlipid componeatsinexposedand pon-expwoorskeerds
PFOA
Sapo
[IminauitrneArie o [a
Nos-FFOA roa
Serva ples oatCost Hol choennt re Non HoL. Cosel Noa HOLADL Tealreeds
maze Be
ws
w
as
wr
mas
ese
ws
ose
mao on
nso
2520
as
rer
wa
on
PemograpicChaat a
wss1o
wares
an
ne
mise ar20s on apse esses on
Jr
otree ornovel men SEM py7 poSn HeoOAS nefom 00 apccolcion
.
LEIS. GM DUPONT LEGAL ETT
wer ro
. SpotcPtorlodisfNt.as5GdniigbolvCaenodrnninadoCnadloolsLLtaaaavvoorroo P Unr i5dpoogeSri ianrdrsdtfVtVs EorRhoOnNaA Cr.cR3AtGGEaTmIRaOyRDSazsn
EE -- Figure1:Correlationsbetween TotalCholesterol Esme (log)and PFOA (log)levelsinthe 4years
I
[i
wa
i
:
ETT
EET EEE `Figure2:Correlations betweennon-HDLCholesterol(log) eadPFOA(log)levelsinthe 4years
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7 [----------
a
vm rennin ta
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&
dat
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:
CY - SEL 15.2007 Q:23MM DUPONT LEGAL ENVITM"TM
. . . Prof.Giovanni Costa
La4tMoodince dorLavooro
TS Ve
or. cAor TniI 0t2b8esa
wus
.
.
In the lightof these findings, G. Olsen (3M epidemiologist) reviewed the 3M datasets relatedtotheirsurveyscarried out in 1993,1996and2000, nd aprelimianzaalyrsyis
concerningcholesterollevelsappearstobeinagreementwith theMitenidata.
Inotherwords,itseemsthatPFOA(probablyonlyathigh blood concentratioenasn)
interferewithmetabolism ofCholesterol,inparticularbyincreasingthefactionof "NenHDL Cholesterol".
`Suchfindingsneed 8preciseinterpretation,alsobecausethey are incontrast with the
animal experimental data(rats), where PFOA causes a decrease ofcholesterol levels.Thatcan
berelatedtointerspeciesdifferencesindrugmetabolism, whicharealsoraisedforthe
differentfindingsincarcinogenicity(it icareinogenin ats,butnotaprimatesandhumans).
Inordertoelucidatebeterthe possible mechanismsunderlyingsucheffect P. Gillies,
DuPontexpert on lipidmetabolism,madeanupdatedreviewofthe curreatknowledgeon
:
lipids metabolism, trying fotakesomehypothesisaboutpossiblemechanists.Accordingto
`his analysis,sucheffectcannotbemediatedby a PPARalfamechanism(assuggestedforrats),
`buritisprobablydueto an interferencewith aprotein (CEPT)able to transfer ofcholesterol
inblaondolivd er, Heisgoing tohave a deeperinsight an suchmatterbothbyfurther
discussionwiththobestacaderny expertsoalipidsandby a biomolecularstudyconceming
thenuclearrecefoprsutchoprortesin.
&Commusanidrcegualatcorlyasopecnts.
RobertRickard(DuPont)saidthti goingtohave aFYI(`Foryourinfomation')
`mestingwith EPAnextWedneAsudguasty25,.
Accordingtothe TSCA $e uleshekas to repos10 EPAstynewdataconcerning.
`possibletoxicological characteristicsof PFOA DuPmaoy kunotw,with perticular refecence to
human bealth.
He exphoissageendda, whichincludesanupdatingof therecenttoxicological snudies.
carried outattheHaskellLabconcemingtheexposureofratsandmicetolinear,branched
`
So
LaJr naE CCfs0m 0CGE eCse GnTMa t,DUPONT LEGAL BWT
wen
LFE i
and mixed (linear/branched) PFOA, as well as thepresentation.ofsome ongoing studies,
dealing
with the health
Virginia, end
examinstion:ofmothre4e 00 workerast DuPont
the reviewof epidemiological datz conceming
"Washington" plant
mortality in geoeral
in West
ZobelGM) villa communica fe
popastion of West Vigiia. G. Olin 12d
epidemiological data concerning 3M workers
L.
at Decatur
and
A
ntw
erp
p
la
nt
s
.
Insuch ageods bewould tketomention slosome fiodings relatedto thedat on pid
metabolism mentioned above, related to Miteni workers, `keeping anomymous the sourceof
data. Inparticular,he wouldlike reportthepositive findingsof alonglastingmedical
uorlvoegiilcsanlcpeoafrsweorrkser,sceoxnpooesrneidotgotBhFeOmAa,nshtaorwgientganrogoofsfactnsdofnugteonenrsa,l heexacletphtafdoral&smoiolnd
possibleinterference withlipid:metabolism, whichdeservesfustheranalysis.
So,beaskedme whethec he can feportsuchdat,inparticular be would like to show
ane oFtwo charts slated to the lidparameters (suches figure 130d 2)fnbispresestaton,
without seutoxiag thesource andthe pameof Mitei, andwithout giving EPA.soy writen
`document. As replied tha 1 couldnotdealwith uchrequest,buthemustaskandge theformal
permissionfromMites Managemen, duetotheshor time availableheaskedme10passyou
uchrequestinonde to getyour Fespomse(Whatever ts) a8soomespossible.
`Withkindregards
Prof.Giovanni Costa
,
Vd
SSE S007 B:04AM DUFONT LEGAL EMTS
`
Pro[ . Giomvanayi Costa
SPEG ipazeeracnr tiidneaooMga el3dSii7dcui1sdnt 5aitddi 1llea!VLas EoLrnaRvevoOnorNersAo
Cr. S CBFCnA ANsAeTC Mr D3ua
move roe
-
Abstractofmy report dated 29.03.04 concerning the meetingofthe APME-APFO
adhoctoxicologygroupo, keldin Beltimore on. March 24.03.04.
cuommemnet5n.e2"cm.TephldWeooryCokefhweearseisr.r(emAasbanohniuoGttletadostsehbmaabtsarmjkuossottsnotfaarbtelhdoeioctdaomlnepdviaenslimkeoesndrimetpeorresisonegmntpeeraddoivginrcatemhcmeoenWicnGemthihenaigdr heparamerees 1becollectedfrom theworkers). Heencoalulcomrpanaiesgtoeshdave otraediirndaattetahientohuetwcaomyetshfaotrMtihteeAniPaMnEdgr3oMuhpa;d|dgoanveehiintmhmeypawsti,elnldihenagflonsroetahssakste.dmeto co-
`As alsoAsahiGlass is sending itssampleto theGerman lab alreadyused by
Solvay, I suggestedthatall European should joia this lab, providedthatit is quite reliable,
1i0ntohrdeeitnttAeorslaicmctioitnoctnheweminftsaohctuloirrpdisadtthmsae,ttcaIaibnonflcoiorsnmmfeodiuntnchadeltlghareborouerpsauttlhitaostn.wwietahnGaelaysriynOgltsheenm(w3iMt)haroefderPeentceer. GiWleldineess(dDauyPomnotr)m;iosgeweitthheGe.nOcllsoesneadnrdeJp.orBtouf tthhe m(ee3enMt)ioanngfdhPfe.ldGstiMaarlnidotGlt.hKoeetnenlesodny (DuPont).'6. KennedyconfirmedthatDuPontisstartingitsbiomonitoringaccordingto the
protocolhecirculatedto thegroupinthelastweek. On Wednesday evening | have been
DiunvPiotendtffoorrcadxcihnsnaegribnygiLnafrorrymatJiaonnsesnb(oLuatwtyheerw)oarknedrRso"bbieormtoRniictkoarridng((sSceieeantcteaDcihreedctroerp)oo).f
AMetettaicnhgmewnitth1.G. Olsen and J. Butenhofl 3M toxicologists), Peter Gillies and J.
Kennedy(DuPonttoxicologists)
"On Wednesds24ymorning, 1 had a 3-hour meetingwithwith 3M and DuPont
toxicologisttodiscussthe preliminary findingsof thedatacollectedin MITENIworkers
andconcerningthe possible interference.ofPFOAwith lipidmetabolism.
G.Olsen havecarried out &preliminary statistical analysis of the biochemicaldata
related to year 2002 and2003, whichshowedsomepossibleslighteffectson HDLand
LDLcholesterol.
lipid
'P. Gillies (DuPont expert
componentsand theirpossible
on lipids)described the
interaction with PFOA.
meaningof
the
different
blood
After along discussion and acareful] analysis of thepresentdats, it hasbeen
conventedoaddfudr atat toh thede atar set, inpardcularthoserelatedtotheongoing
`biomonitoring whichis due toend byApril. Inthis surveyfurtheranalysisoflipidsand
proteins (LDL.Cholesterol, APO-A2, APO-B, reactive C-protein) have been add in oerdder
toclarify better such interaction.
So, I agreed insending them suchnew dats by theead of April andthen start 3
deeperstatistical analysis. `The results are expected
to
be
sent
to
2
toxicology
jouraal
for
publicatiboyn
the
endof the year.
5 TOTAL P10
72