Document MJvRkQQ5xxr2Y9NrD70nmnRXM

+ . 33PMagCCeoonLmgopaarrn)yy Page t of 63 ( EpidFFeIImNNiAoAlLLogRRyEE,PP2O2O0RR-TT3W-05 Ep`MMideeeddmiicciaaollloDDgeeypp,aa2rr2tt0mm-e3enWntt-05 33MM CCoommppaannyy SStt.. PPaual,ul, MMNN 5555114444 `DDaattee:: OOccttoobbeerr 1111,,2001" "Tie: A Longitudinal Analysoifs Serum Perfluorooctnesulfonae (PFOS)and Title: A Longitudinal Analysis of Serum Perfluorooctanesulfonate (PFOS) and PPeerrfflluuocrrooooccttaannooaatte ((PPFFOOAA)) LLeevveellss iinn RReellaattiioonn ttoo LLiippiidd aanndd HHeeppaattiicc CClliinniiccaall CChheemmisisttrryy Test Results from Male Employee Participants of the 1994/95, 1997 and 2000 Test Results from Male Employee Participants of the 1994195, 1997 and 2000 FFlluuoorroocchheemmiiccaall MMeeddiiccaall SSuurrvveeiillllaannccee PPrrooggrraamm SSStutuunddDyyue: Jul1y, 2001 Start Date: J'.uly I, 2001 IRPPrrBoottooAccpoopllrNNovuuammlbbeerr(r(noott aspppplliiccaabbllee)) IRBEEAxxpeepxmmrpoptvtal Eoedited X IIRRBB AApppprroovvaallDDaattee:: ((nroott aapppplliiccaabbllee aas tthheesseeddaattaaaarr~ ffrroomm aa mmeeddiiccaall ssuurrvveeiillllaannccee. pprrooggraamm)) PrPirnincciippaall IInnvveesstitiggaattoorr:. CCoo--iinnvveessttiiggaattoorrss:: SSttuuddyyDDiri~ec'cttoor~:. GGeaearryyWW.. OOllsseenn,,DD..VV.AM4..,, PPhhD.D.) `MMiicchheellee MM.. BBuurrlieeww,, MM.S.S.'J JJJeeefaafnnreMMy.H. .BBuMurrni'iass,, RRnN..N,M.d,MDMPe,.PHM.Hl.P.IH,. Jeffrey H. Mandel, M~D., M.P.H.I JJeefffrferyeHHy.. MMaandenl, MMdD.D.e., MMlP.PH.,.H". 1. 3M Medica Department, 220-3W-05, St. Paul, MN 55144-1000 I. 3M Medical Department, 220-3W-05, St. Paul, MN 55144-1000 *"((CCoorrrreeccttiioonnssmmaaddeeffrroomm pprreevviioouuss vveerrssiioonn)) ( Exhibit 1799 11779999..00000011 W3M_MNM0N204284822116633 3PMeCgoemlpaonEy Page 2 of 63 AABBSSTTRRAACCTT `TThhee 33MM fflluuoorr~ccchheemmiiccaall mmeeddiiccaall ssuurrvveeiillllaannccee pprroo.mgr"aamm wwaass ccoonndduucctteedd iinn t1999944//9955,, 11999977 2an1dd 22000000 aatttthhee ccoommppaannyy''ss AAnnttwweerrpp ((BBeellggiiuumm)) aanndd DDeeccaattuurr ((AAllaabbaammaa)) mmaannuuffaaccttuurriinngg ppllaannttss.. AAlltthhoouug~h ccrroossss--sseeccttiioonnaall aasssseessssmmeennttssofoftthhee ddaatta hhaavvee been rreeppoorrtteedd,, tthhee ooppppoorrttuunniittyy ttoo ccoonndduucctt aa lloonnggiittuuddiinnaall aasssseessssmmeenntt bbeeccaammee ppoossssiibbllee asss aa rreessuulltt of of a large large nnuummbbeerrooffeemmppllooyyeese ppaarrtiicciippaannttss in in the the 2000 2000 fflluuoorroocchheemmiiccaall mmeeddiiccaall ssuurrvveeiillllaannccee pprrooggrraamm.. AA ttoottaall ooff 117755 mmaallee eemmppllooyyeeeess vvoolluunnttaarriillyy ppaarrttiicciippaatteedd iinn tthhee 22000000 pprrooggrraammaannddatatleleaasstt oonneeoofftthhee ttwwoopprreevviioouusspprrooggrraamm yyeeaarrss.. AAtotottaallooff110066 ((6611ppeerrcceenntt)) of the of the 175 175 employees employees ppaarrttiicciippaatteedd in in the the 1994/95 1994/95 program program and and 110 (63 percent) of the 1 l0 (63 percent) of the 175 175 ppaarriticiippaaiteeddiinn the the 11999977 pprrooggrraamm,. Of Of tthheessee 175 175 eemmppllooyyeeeess,, a a toalof total of 41 41 (24 (24 ppeerrcceenntt)) ppaarrttiicciippaatteedd iinn aallll tthhrreeee yyeeaarrss ((AAnnttwweerrpp == 2211,, DDeeccaattuurr == 2200)),, 6655 ((3377 ppeerrcceenntt)) ppaarrttiicciippaatteedd iinn 11999944/9955 aanndd 22000000 ((AAnnttwweerrpp == 4455,, DDeeccaattuurr ==2200)) anndd 6699 ((3399 ppeerrcceenntt)) ppaarrtiiciippaatteeddiinn 11999977 aanndd 22000000 ((AAnnttwweerpr==p 3344,, DDeeccaattuurr = - 3355)).. TThheerree wweerree iinnssuuffffiicciieenntt nnuummbbeerr of of ffeemmaalele. eemmplpoyleesottooyccoeonndeduucsctt aannyy mmeeaannining~fuull lloonng~ittuuddiinnaall ~assseessssmmeenntt.. OOnnllyy 1144 ffeemmaallee eemmppllooyyeeeess ppaarrttiicciippaatteedd iinntthhee22000000 fflluuoorroocchheemmiiccaall mmeeddiiccaall ssuurrvveeiillllaannccee pprrooggrraamm and and at at lleeaasstt oonneeoofftthhee pprreevviioouuss pprrooggrraamm yyeeaarrss.. `SSeerruumm ppeerffflluuorrooooccttaanneessuullffoonnaattee ((PPFFOOS$)) aanndd ppeefrflluuoorrooooccttaannooaattee ((PPFFOOAA)) wweerree assayed in each surveillance program year although the method of analysis (high assayed in each surv,eillance program year although the method of analysis (high ppeerrffoorrmmaannccee lliiqquuiidd chhr.roommaattooggrraapphhyy mmaassss ssppeeccttrroommeettrryy)) ddiiffffeerreedd ssllii~ghttllyy bbeetcwweeeenn yyeeaarrss.. A different research laboratory was usd 0 assay PFOS and PFOA in each year. A different research laboratory was used to assay PFOS and PFOA in each year. T"Thhee ssaammee hhoossppiittaall llaabboorraattoorryy aannaallyyzzeedd tthhee cclliinniiccaall cchheemmisisttrriieessffoorraallll tthrree~e ssuurrvveeiillllaannccee yyeeaarrss., TThheessee iinncclluuddeedd:: cchhoolleessteerrooll ((mmg~/ddl)., hhiigghh ddeennssiittyy lliippoopprrootleeiinnss ((HHDDLL., ( 11779999..00000022 33MM_MMNNo022e48822116644 33PMuCCsoo3mm0ppraa6nn3yy Page 3 or 63 mmg~/ddll)) aanndd trriiggllyycceerriiddeess ((mmg~/ddl):; aallkkaalliinnee pphhoosspphhaattaassee ((IIUU//LL)),, ggaammmmaa gglluottaammyyll ttrraannssffeerraassee ((GGGOTT., TIUUL/L)),, aassppaarrttaattee aammiinnoottrraannssffeerraassee ((AASSTT,, I[UU//LL)),, aallaanniinnee aammiinnoottrraannssffeerraassee ((AALLTT,, II'UU//LL)).. ttoottaall aanndd ddiirreecct bbiilliirruubbiinn ((mmg~/dd)l.). MMoosstt rreeffeerreennccee rraannggeess rreemmaaiinneeddrreelliaitivveellyyccoonnssatann:t oovveertdiimneeeexxcceepptt ffoorr AALLTT.. IInn eeaacchh ssuurrvveeiillllaannccee yyeeaarr,, `ppootteennttiiaall ccoonnffoouunnddiinngg ffaaccttoorrss wweerree aallssooddeetteerrmmiinneedd.. TThheessee ccoovvaarriiaatteess iinncclluuddeedd aaggee,, bbooddyy `mmaassss iinnddeexx,, nnuummbbeerrooffaallccoohhoolliicc ddrriinnkkss ppeerr ddaayy aanndd cciiggaarreetttieess ssmmookkeedd ppeerr cdaayy.. TThhee ccoonnttiinnuuoouuss oouuttccoommeessooff lliippiidd aannddhehpeaptaiticccclliinniiccaall cchheemmiissttrryy tteessttss wweerree eevvaalluusaiteedd aass rreeppeeaatteedd mmeeaassuurreess iinnccoorrppoorraattiinngg tthhee rraannddoomm ssuubbjjeecctt eeffffeecctt ffiitteedd t1o0 aa mmiixxeedd mmooddeell bbyy tthhee MMI!XXEEDD pprroocceedduurree iinntthhee SSAASS ssttaattiissttiiccaall ppaacckkaaggee.. RReessttrriicctteedd mmaaxxiimmuumm lliikkeelliihhoooodd eessttiimmaatteess of of vvaarriiaannccee ppaarraammeetteerrss were were ccoommppuutteedd.. AAddjjuusstteedd rreeggrreessssiioonn mmooddeellss wweerree bbuuiilltt bbyy iinntdrroodduucciinngg aallll ccoovvaarriiaatteessaannddtteessttiinngg tthhee ccoovvaarriiaannccee ssttrruuccttuurree.. SSiiggnniiffiiccaanntt ccooeeffffiicciieennttss wweerree ddeeffiinneedd wwhheenn tthhee p vvaalluuee wwaass << .0055.. ( TThheerree wwaass aa ppoossiitiivvee aassssoocciiaattiioonn bbeevtwweeeenn PPFFOOAA aanndd sseerruumm cchhoolleesstteerrooll aanndd twriiggllyycceerriiddeess oovveerr ttiimmee bbuutt nnoott wwiitthh PPFFOOSS.. TThhiiss wwaass aassssoocciiaattiioonn wwaass lliimmiitteedd to tthhee AAnnttvw,e'errpp eemmppllooyyeeeess and, and, in in ppaarrttiiccuullaarr,, the the 21 21 AAnnttwweerrpp eemmppllooyyeeeess who who ppaarrttiicciippaatteedd inal in all tthhreeee ssuurrvveeiillllaannccee yyeeaarrss.. Ths This ppoossiittiivvee aassssoocciiaattiioonn bbeettwweeeenn PPFFOOAA and and sseerruumm lliippiiddss is is ooppppoossiittee tthhe iinnccoonnssiisstteenntt ttooxxiiccoollooggiiccaall eevviiddeennccee tthhaatt ssuuggggeesstteedd a a ppoossssiibbllee hhyyppoolliippiiddeemmiicc effect effect of PFOA in of PFOA in rodents and no effec rodents and no effect in primates. in primates. Adjusting Adjusting for for potential potential ccoonnffoouunnddeerrss,, tthheerree wweerree nnoo tteemmppoorraall cchhaannggeess aassssoocciiaatteedd wwiitthh tthhee fflluuocrroocchheemmiiccaall tteesstss,, PPFFOOSS., PPFFOOAA and TOF. and the hepatic clinical chemisry tests. and TOF. and the hepatic clinical chemistry, tests. LLiimmiittaattiioonnss ooff tthhiiss ssttuuddyy iinncclluuddeedd tthhee nnuummbbeerr oOffeemmplpoloyyeeeess wwiitthh tthhrreeee yyeeaarrss ooff ssuurrvveeiillllaannccee data data (only (only 245% 24% of of the the 175 175 ssuubbjjeeccttss)),, the the iinnaabbiilliittyy to to aannaallyyzzee tteemmppoorraall cchhaannggeess duet due to small small nnuummbbeerr~s in in female female eemmppllooyyeeess,, the the uusseeooffddiiffffeerrenntt llaabboorraattoorriieess and and 11779999..00000033 I3MM_MMNN0022448822116655 : 33PMMagCCeootmmpopalann)yy Pag~ 4 of 63 tthhee aassssoocciiaatteedd ssyysstteemmaattiicc ((eexxppeerriimmeennttaall eerrrroorr)) wwiitthh eeaacchh fflluuoorroocchheemmiiccaall aassssaayy ffoorr t~hhee tthhrreeee ssuurrvveeiillllaannccee pprroosg~raamm yyeeaarrss aanndd tthhee lloowweerr lleevveellss ooffsseerruumm PPFFOOSS aanndd PPFFOOAA . mmeeaassuurreedd iinn eeaacchh pprroo.g~r'aamm yyeeaarr aammoonngg tthheessee eemmppllooyyeeeess ccoommppaarreedd wwiitthh t~hoossee tthhaatt ccaauussee: eeffffeeccttss iinn llaabboorraattoorryy aanniimmaallss.. 11779999..00000044 I3MM_MMNND022448822116666 IkNNTTRROODDUUCCTTIIOONN 33PMagCCeoo3mm0ppraa6nnsyy Page 5 of 63 "TThhee 33MM Afluuoorroocchheemmiiccaall mmeeddiiccaall ssuurrvveeiillllaannccee pprrooggrraamm iiss ccoonndduucctteedd oonn aa rroouuttiinnee bbaasissaatitthtshee ccoommppaannyy''ss AAnnttwweerrpp ((BBeellg~iuurmn)) aannddDDeceactauturr((AAllaabbaarmaaa)) mmaannuuffaaccttuurriinngg ppllaanntsts,. EEmmppllooyyeese ppaar.niicciippaattiioonn iiss vvoolluunnttaarryy.. PPrrioirotroo 11999944,, o0nnllyy otottaall oorrggaanniicc fflluuoorriinnee wwaass mmeeaassuurreedd aanndd nnoo ssppeecciiffiicc flluuoorroocchheemmiiccaall aannaallyytteess wweerree mmeeaassuurreedd.. SSeerruumm perfluorooctanesulfonate perfluorooctanesu[fonate (PROS) (PFOS) aanndd ppeerrfflluuoorrooooccttaannooaattee ((PPFFOOAA)) hhaavvee bbeeeenn rroouuttiinneellyy aassssaayyeedd ssiinnccee 11999944//9955 rraatthheerr tthhaann ttoottaall oorrggaanniicc fflluuoorriinnee aass tthheeanaanlayltyiticcaall ccaappaabibliiltitiieess hhaavvee: iimmpprroovveedd.. CCrroossss--sseeccttiioonnaall aannaallyysseess ooftf thhee 11999944//9955 aanndd 11999977 mmeeddiiccaall ssuurrvveeiillllaannccee: pprrooggrraamm ddaattaa aanndd tthhee 22000000 ddaattaa iinn rreellaattiioonn ttoo AAnnttwweerrpp aannddDDeeccaattuurreemmppllooyyeeess'' sseerruumm PPFFOOSS lleevveellss hhaavvee bbeeeenn rreeppoorrteedd eellsseewwhheerree ((OOllsseenn cett aall,, 11999999aa,, 11999999b,, 22000001)).. IInntthhee 11999944/11999955 mmeeddiiccaall ssuurrvveeiillllaannccee pprrooggrraamm,,aa ttoottaall ooff 117788 mmaallee eemmppllooyyeeeess ppaarrtiicciippaaiteedd ((AAnnttwweerrpp == 8888;; DDeeccaattuurr =-- 9900)) aanndd 114499 mmaallee eemmppllooyyeeeess ppaarrttiicciippaatteedd iinn tthhee 119999"7] pprrooggrraamm (Antwerp = 65; Decatur = 34). For these two program years, there were too few female (Antwerp = 65; Decatur = 8~t). For these two program years, there were too few female ppaarrttiicciippaannttss ttoo iinncclluuddee iinntthhee ddaattaa aannaallyyssiiss ((OOllsseenn eett aall 11999988)).. IInn tthhee 22000000 fflluuoorroocchheemmiiccaall mmeeddiiccaall ssuurrvveeiillllaannccee pprrooggrraamm., tthheerree wweerree ccoonnssiiddeerraabbllyy mmoorree ppaarrttiicciippaannttss:: 442211 mmaalleess ((AAnnttwweerrpp == 220066;; DDeeccaattuurr == 221155)) aanndd 9977 ffeemmaalleess ((AAnnotwweerrpp =-- d49g;; DDeeccaaturr== 4488)).. IItt wwaass suspected that the increased voluntary participation in 2000 was due to increased suspected that the increased voluntary participation in 2000 was due to increased employee awarenessofth persistence and prevalence of PFOS in human tissue and the employee awareness of the persistence and prevalence of PFOS in human tissue and the eennvviirroonnmmeenntt aanndd tthhee ccoommppaannyy''ss MMaayy 1166.. 22000000 pphhaassee oouutt aannnnoouunncceemmeenntt tthhaatt iitt wwoouulldd cease the production ofperluoroocianyl chemistry in certain repellents and surfactants cease the production o(pcrfluorooctanyl chemistry in certain rcpcllent~ and surfactants by the end of 2000. by the end of 2000. RReeggaarrddlleessssoofftthhee ssuurrvveeiillllaannccee yyeeaarr,, tthheerree hhaavvee bbeeeenn sseevveerraall ccoonnssiisstteennttddiiffffeerreenncceess. bbeettwweeeenn tthhee AAnnttwweerrpp aanndd DDeeccaattuurr mmaallee eemmppllooyyeeee ppooppuullaattiioonnss.. TThhee AAnnttwweerrpp mmalaele: 11779999..00000055 IM_MNo2482167 3M MN02482167 3MPMCaogCemo0pm1ap6ann3yy Page 6 of 63 eemmppllooyyeeee ppooppuullaattiioonn hhaass bbeeeenn ssii~gniiffiiccaannttllyy yyoouunnggeerr tthhaann DDeeccaattuurr,, hhaass hhaadd lloowweerr BBooddyy. MMaassss IInnddiicceess((BBMMDI) aanndd hhiigghheerr sseellff--rreeppoorrtteedddadaiillyyccoonnssuummppttiioonn ooff aallccoohholo.l. IInn aaddddiittiioonn,, tthhee AAnnttwweerrpp mmaallee eemmppllooyyeese ppooppuullaattiioonn cclliinniiccaall cchheemmisisttrryy pprrooffiilleess wweerree ddiiffffeerreenntt ffoorr sseevveerraall tteessttss iinncclluuddiinngg lloowweerr mmeeaann aallkkaalliinnee pphhoosspphhaattaasse aanndd ttrriiggllyycceerriiddee vvaalluueess aanndd hhiigghheerr ttoottaall bbiilliirruubbiinn aanndd IH-IDDLL vvaalluueess tthhaann tthhee DDe~ccaattuurr mmaallee eemmppllooyyeeee ppooppuullaattiioonn.. AAnnaallyysseessooff wwoorrkkeerrss' lliippiidd aanndd hheeppaatiicc cclliinniiccaall cchheemmiissttryy rr~essuullttss hhaavvee nnoott bbeeeenn aassssoocciiaatteedd wwiitthh hhyyppoolliippiiddeermniicc eeffffeeccttssaanndd PPFFOOSS aass rreeppoorrtteedd iinn rrooddeennttss ((33MM CCoommppaannyy 22000000;; `HHaauugghhoomm aanndd SSppyyddeevvoolldd 11999922:; Iekdedaa ectt aall 11998877;; PPaassttoooorr cett aall 11998877:;SSeeaaccaattcett aall 220000118a;; `SSoohhlleenniiuuss eettaall 11999933)) aanndd pprriimmaatteess ((SSeeaaccaatt tetaall 22000011b)).. IInn tthhee 22000000 mmeeddiiccaall ssuurrvveeiillllaannccee: pprrooggrraamm,, ssttaattiissttiiccaall aannaallyysseess aallssoo eexxaammiinneedd tthhee rreellaattiioonn bbeettwweeeenn PPFFOOAAaannddaa ccaallccuullaatteedd ttoottaall oorrggaanniicc fflluuoorriinnee iinnddce.xx ((TOTF)tOtoocclPliinnii)ccaall cchheemmisitsrtriieess,, hheemmaattoollooggyy,, tthhyyrrooiiddhhoorrmmoonneess aanndd uurriinnaallyysseess ((OOllsseenn eettaall 22000011)).. AA ppoossiittiivvee aassssoocciiaattiioonn wwaass oobbsseerrvveedd bbeettwweeeenn ( ttrriiggllyycceerriiddeess aannddPPFFOOAA:; hhoowweevveerr,, tthhiiss aassssoocciiaattiioonn wwaass ooppppoossiittee tthhee ddaattaa tthaatt hhaavvee iinnccoonnssiisstteennttllyy rreeppoorrtteeddaa hhy.vppoolliippiiddcemmiiaa eeffffeecctt ooffPPFFOOAA iinn rrooddeennttss ((HHaauugghhoormn aanndd SSppyydcelevvoolldd 11999922;; PPaassttoooorr eetaall 11998877)) aanndd nnoo eeffffeecctt iinn pprriimmaatteess ((BBuutteennhhoofffeeftt al al 2001). 2001). FFuurrtthheerrmmoorree,, tthhiiss ppoossiittiivvee aassssoocciiaattiioonn bbeettwweeeenn PPFFOOAA aannddttrriiggllyycceerriiddeess hhaass nnoott bbeeeenn oobbsseerrvveedd aait tthhee 33MM CCoonttaaggee GGrroovvee mmaannuuffaaccttuurriinngg ppllaanntt ((OOllsseenn eettaall 2200(0300)) wwhheerere. eemmppllooyyeeeess'' sseerruumm lleevveellss hhaavvee,, hhiissttoorriiccaallllyy,, bbeeeenn mmuucchh hhiigghheerr tthhaann tthhoossee mmeeaassuurreedd aammoonngg AAnnttwweerrpp aanndd DDeeccaattuurr eemmppllooyyeeeess ((OOllsseenn eett aall 11999999;; 220000113a;; OOllsseenneet aall 220000110b)).. "The inabilityto,assess temporal changes in cross-sectional studies is a well- The inability to, assess temporal changes in cross-sectional studies is a well- kknnoowwnn lliimmiitactaioonn ooff tthhiissddeessiiggnn..TThhee llaarrggee ppaarrtiiicippaattiioonnooff eemmppllooyyeeeess iinn tthhee 22000000 Afluuoorroocchheemmiiccaall mmeeddiiccaall ssuurrvveeiillllaannccee wwhhoo mmaayy hhaavvee ppaarrttiicciippaatteedd iinn tthhee 1199994ad/9955 aannddl/oorr 1199997"/ssuurrvveeiillllaannccee pprrooggrraammss aatt tthheessee ttwwoo mmaannuuffaaccttuurriinngg ssittess aalllloowweedd ffoorr aann ooppppoorrttuunniittyy 11779999..00000066 I3MM_MMNN0022448822116688 3 Company 3M Company Faeroe Page 7 ot'63 0to ccoonndduuccttaa lloonnggiittuuddiinnaall aannaallyyssiiss aammoonngg tthhee mmaallee eemmppllooyyeese ppooppuullaattiioonn.. AAllttooggeetthheerr,, aa ttoottaall ooff 117755 eemmppllooyyeeeess ((AAnnttwweerrpp == 110000;; DDeeccaattuur=r= 7755)) wwhhoo ppaarriticciippaatteedd iinn 22000000 hhaadd aallssoo. ppaarrttiicciippaatteedd iinnaat lleeaasstt oonnee pprreevviioouuss fflluuoorroocchheemmiiccaall mmeeddiiccaall ssuurrvveeiillllaannccee eexxaamm ssiinnccee 11999944/~9955.. TThheerreeffoorre,, tthhee ppuurrppoossee ooff tthhiiss aannaallyyssiiss wwaasstto ccoonndduuccttaa lloonnggiittuuddiinnaall aasssseessssmmeenntt ooff tthhiiss 66 yyeeaarr ttiimmee ppeerriioodd rreeggaarrddiinngg tthhee rreelaltaioinosnhsiphoiofpf PPFFOOSS,, PPFFOOAA aanndd TTOOFF ttootthhee mmeeddiiccaall ssuurrvveeiillllaannccee ddaattaa ccoolllleecctteedd oonn tthheessee 117755 AAnnttwweerrpp aanndd DDeeccaattuurr mmaallee employees. employees. MMEETTHFIOODDSS 3 DaDtaamCColollleeccttiioonn `DDaattaa wweerree ccoommppiilleedd ffrroomm tthhee 11999944/9955,, 11999977 aanndd 22000000 fflluaoorroocchheermri~ccaall mmeeddiiccaall surveillance program databases. A total of 175 male employees paricipatedin the 2000 surveillance prob.'am databases. A total of 175 male employees participated in the 2000 pprrooggrraamm aannddaat lleeaasstt oonneeoofftthhee ttwwoo pprreevviioouuss pprrooggrraamm yyeeaarrss.. AA ttoottaall ooff 110066 ((6611 ppeerrcceenntt)) oofftthhee 117755 eemmppllooyyeeeess ppaarrtiiciippaatteedd iinn tthhee 11999944//9955 pprrooggrraamm aanndd 11I100 ((6633 ppeerrcceenntt))oofftthhee: 117755 ppaarrttiicciippaatteedd iinn tthhee 11999977 pprrooggrraamm..OOfftthheessee 117755 eemmppllooyyeeeess., aa ttoottaallooff 4411 ((2244 ppeerrcceenntt)) ppaarrttiicciippaatteedd iinn aallll ttl'hue'cee yyeeaarrss ((AAnnttwweerrpp -=- 2211,, DDeeccaattuurr ==2200)),, 6655 ((3377 ppcenr:cenet)) ppaarrtiicciippaaiteedd iinn 11999944//9955 aanndd 22000000 ((AAnnttwweerrpp == 4455,, DDeeccaatturu==r 2200)) aanndd6699 ((3399 ppeerrcceenntt)) ppaarrttiicciippaatteedd iinn 11999977 aanndd 22000000 ((AAnnttwweerrpp == 3344,, DDeeccaattuurr == 3355)).. FFoorr ppuurrppoosseess ooffbbrreevviittyy,, tthheessee tthhreeee ssuubbppooppuullaattiioonnss wwiillll hhearte,aaffiteerr bbe rreeffeerrreedd ttoo aass ssaubbccoohhoonrttss AA,, BB aanndd CC.. `DDeemmoog.mra'apphhiicc dda~ttaa ((aaggee., BBMMYI,, aallccoohhoolliicc ddrriinnkkss ppeerr ddaayy aanndd cciiggaarreettteessppeerrddaayy)) wweerree rreeccoorrddeeddffoorrceaacchh eemmppllooyyeeee iinn eeaacchh ssuurrvveeiillllaannccee yyeeaarr.. AA ssttaannddaarrdd sseettooffcclliinniiccaall cchheemmisisttrriieess aanndd hheemmaattoollooggyy, ddaattaa wwaass aallssoo oobbataiinneeddffoorreeaacchh eemmppllooyyeeee.. GGiivveenn rreessuullttss ffrroomm pprreevviioouuss ttooxxiiccoollooggiiccaall ssttuuddiieess,, tthhee lloonnggiittuuddiinnaall aannaallyysseess ffooccuusseedd oonn lliippiidd 11779999..00000077 I3MM_MMNN0022448822116699  . 33PMMaCCsootmmpepalannsyy Page 8 of 63 c[chholoelesstteerrooll ((mmg~/dd)l)., hhiigghh dde~nnssiityy lliippoopprrootteeinins ((IH-IDDLL,, mmg~ddl)) aanndd tirgiglylycceerdiddeess ((mmg~/ddl))] aanndd hheeppaattiicc a[allkkaalliinnee pphhoosspphhaattaasse ((II'UU//LL)),, ggaammmmaagglluuttaammyy)l ttrraannssffeerraassee ((GGGGTT,, TIUUL/L)),, aassppaarrttaattee aammiinnoottrraannssffeerraassee ((AASSTT,, [I'UUI/LL)),, aallaanniinnee aammiinnoottrraannssffeerraassee ((AALLTT,, IIUUI/LL)),, ttoottaall aanndd. ddiirreecct bbiilliirruubbiinn ((mmgg/lddl)]] cclliinniiccaall cchheemmisisttrriieess tthhaatt wweerree mmeeaassuurreedd iinn eeaacchh pprrooggrraamm yyeeaarr bbyy tthhee ssaammee llaboaratboryo((AAlrllliinnaaaLLatbaobrooartaortorriieyess,, SStt.. PPaaulu,l,MMN)N.). RReeffeerreennccee rraannggeess wweerree rreellaattiivveellyy ccoonnssttaanntt oovveerr ttiimmee,, aalltthhoouug~h ffoorr AALLTT tthhee rraannggee ddeecclliinneedd ffrroomm 2200.-6655 ITUU!LL iinn 11999944//99551t0o 11.-4400 ITUU/LL iinn 11999977 aanndd22000000.. `FFlluuoorroocchheemieicaallAAnnaallyysseess PPFFOOSS aanndd PPFFOOAA wweerree aassssaayyeedd nin 11999944//99.55,, 11999977 aanndd 22000000.. HHoowweevveerr,, tthhee mmeetthhoodd ofof aannaallyyssiiss ddiiffffeerreedd sslliigghhttllyy ffoorreeaacchh yyeeaarr.. IInn 11999944//9955,, tthheemmetethhoodduusseedd `tet~e'tarbaubtyultaynl,ahm-nmoonniiuumm ttoo ioonn--ppaaiirrwwiitthh PPFFOOSS aanndd PPFFOOAA iinn tthhee sseerruumm ((.J]'oohhnnssoonn eett aall 11999966)).. T"Thheefioonn.-ppiarirss wweerree tthheenn eexxttrraacctteedd wwiitthh ee~thhyyll aacceettaattee,. TThhee aabbssttrraaccttiioonn pprroodduuccttwwaasstthheenn aannaallyyzzeedd uussiinngg hhiigghh--ppeerrffoorrmmaannccee lliiqquuiidd cchhrroommaattooggrraapphh--thheerrmmoosspprraayy mmaassss ssppeeccttrroommetertryy.. IInn 11999977,, tthhee sseerruumm ssaammpplleess wweerree aannaallyyzzeedd bbyylliiqquuiiddcchhrroommaattooggrraapphhyy//mmaassss ssppeeccttrroommeettrryy,, uussiinngg sseelleecctteedd iioonn mmoonniittoorriinngg iin tthhee nneeggaattiivvee--iloonn mmooddee ((AAnnddeerrssoonn aanndd MMuullvvaannrnaa 119999778a;; 119999776b)).. IInn 22000000,, sseerrea ssaammpplleess wweerree eexxttrraacctteedd uussiinngg aann iioonn--ppaaiiriinngg eexxttrraaccttiioonn pprroocceeddmur'e ((HHaannsseenn eettaall,, 22000011)).. OOrnllyy iinn22000000wweerree tthhee eexxttrraaccttss qquuaannttiittaattiivveellyy aannaallyyzzeedd ffoorr PPFFOOSS aanndd PPFFOOAA aass wweellll aasstthhee ootthheerr aannaallyytteess:: PPFFHHSS,~(p(eprefrlfluuoorroohherxxaanneseusluflfoonnaattee)),, PPFFOOSSAAAA ((NN-eetthhyyll ppeerrfflluuoorrooooccttaanneess,yullffoonnaammididooacaecteatattee)),, MMS5T700 ((NN--mmeetthhyyll ppeerrfflluuoorrooooccttaanneessuullffoonnaammiiddooaacceettaatte)),, PPFFOOSSAA ((ppeerrfflluuoorroooncctiaanneessuallffoonnaatteeaammiiddee)) aanndd MMS5S566 ((ppeerrffluuoorrooooccttanneessuullffoonnaammiiddooaaccecatraete)).. HHigighh--ppe~rrffoorrmmaanncceeliliqquuiidd cchhrroommaattooggrraapphhyy/e/elleeccttrroosspprraayy ttaannddeemm mmaassss ssppeeccttrroommeettrryy ((IH-IPPLLOC//EESSMMSSMMSS)) wwaass tthhee 11779999..00000088 3M_MNo2482170 3M MN02482170 35PMMagCCeoosmmppoanrnn6yys Page g of 63 , tteecchhnniiqquuee uusseedd iinn 22000000.. TThhee ssaammpplleess wweerree eevvaalluuaatteedd vveerrssuuss aanneexxttrraacctteedd ccuurrvvee ffrroomm aa hhuummaann sseerruumm mmaatiriixx.. AAnnaallyysseess wweerree ccoonndduucctteedd aatt ddiiffffeerreenntt llaabboorraattoorriieess iinn tthhee. tthhrreeee ssuurrvveeiillllaannccee yyeeaa~rss.. FFoorr ppuurrppoosseessooff tthhiiss lloonnggiittuuddiinnaall aannaallyyssiiss,,aatottotaall oorrggaanniicc fflluuoorriinnee iinnddeexx ((TTOOFF)) wwaass ddeetteerrmmiinneedd bbyy ccaallccuullaattiinngg tthhee ppeerrcceenntt ooff PPFFOOSS aanndd PPFFOOAA tthhaatt wwaass attrtirbiubutteedd ttoo oorrggaanniicc fflluuoorriinnee ((6644..'77 aanndd 6699..00 ppeerrcceenntt,, rreessppeeccttiivveellyy)) mmuullttiipplliieedd bbyy tthhe ppppmm. mmeeaassuurreedd ffoorr eeaacchh ooff tthheessee ttwwoo fflluuoorroocchheemmiiccaallssaanndd tthheenn ssuummmmeeddttoopprroodduucceeththeeTTOOFF.. DaDtaataAAnanlaylyssiiss BBrriieeffllyy., mmiixxeedd mmooddeellss ccaann bbee uusseedd iinn tthheeaannaallyyssiiss ooff rreeppeeaatteedd mmeeaassuurreess ddaattaa `wwhhiicchh aarre ssiimmppllyyddaattaasesettss wwiitthh mmuultltiippllee mmeeaassuurreemmeennttssooff aa rreessppoonnssee vvaarriiaabbllee oonn tthhee same same ssuubbjjeecctt over over time. time. DDeettaailleedd eexxppllaannaattiioonn of of tthheessee mmooddeellss iisspprroovviiddeedd eellsseewwhheerree (Lill 1996; 2000) (Littell 1996; 2000). Mixed Mixed models models contain contain fctor factor effects effects which which are are ccoonnssiiddeerreeddbbootthh ( fined fixed and and rraannddoomm.. An An eeffffeecctt sis fixed fixed if if the the lleevveells in in the the ssttuuddyyrreepprreesseenntt all all ppoosssiibblee lleevveellss ofthe of the ffaaccttoorr,, orai or at leas all least all lleevveellss about about wwhhiicchh iinnffeerreennccee sis tbe to be mmaaddee.. FFaaccttoorr eeffffeecttss are are rraannddoommif ift~hhelelevveellss ooff tthhee ffaaccttoorr tthhaatt aarree uusseeddiin tthhee sstuuddyy rreepprreesseenntt oonnllyy aa rraannddoomm ssaammppllee ooffaa llaarr~geerr sseett ooffppooetneinitiaall lleevveellss.. "TThheeffooccuussoofftthheessatannddaarrddlilinneeaarrmmooddeelliiss ttoommododeelltthheemmeeaannooff yybbyyusuisinngg tthhee ffiixxeedd--eeffffeeccttss ppaarraammeetteerrss ~8).. TThhaattiiss,, yy==XXa~++e~ wherey represents a vectorofobserved data is an unknown vector of fixed effects where y represents a vector or" observed data, ~ is an unknown vector of fixed effect~ ppaarraammeetteerrss with wi~ known kno~n design design matrix matrix X, X, and and & ~ is is an an unknown unknown random errorvector random error vector mmooddeelliinngg tthhee ssatattiisstticcaall n"nooiissee' aarroouunndd XXBj~.. TThhee rreessiidduuaall eerrroorrss ~ aarree aassssuummeedd to to be: be 11779999..00000099 33MM_MMNNo022448822117711 P33MuMcCCoolnmoppaoarnryy Page I0 of 63 iinnddeeppeennddeenntt and and iiddeenntiiccallllyy ddiissttrriibbuutteedd GGaauussssiiaann rraannddoomm vvaariiaabbleess wwiitthh mmeeaann 00 eanndd vv~arsiiannccee 0o%-.. AA ggeenneerraalliizzeedd ssttaannddaarrdd lliinneeaarr mmooddeel iissaa mmiixxeedd mmooddeell wwhhiicchh iiss:: yy ==XX#pr+ zZyy+re wwhheerree y iiss aann uunnkknnoowwnn vveeccttoorr ooff rraannddoomm--f~fffeeccttss ppaarraammeetteerrss wwiitthh kknnoowwnn ddeessiiggnn mmaattriixx Z2,, aanndd ~ iiss aann uunnkknnoowwnn rraannddoomm eerxroorr vveeccttoorr wwhhoossee eell~e-mneennttss aarme nnoo lloonnggeerr rreeqquuiirreedd ttoobbe~ iinnddeeppeennddeenntt and and hhoommooggeenneoeousu.s. If If y y + + & E are ar~ aassssuummeeddttoobbe~ GGaauussssiiaann rraannddoomm vvaarriiaabblleess "ththaatt aarree uunnccoorrrreellaatteedd aanndd hhaavvee eexxppeeccttaattiioonnss 00 aanndd vvaarriiaanncceess GG aanndd RR,, rreessppeeccttiivveellyy,, tthheenn the the vvaarriiaannccee of ys: ofy is: VV == 2~6GZZ' +R + R "TThheevvaraiancreoofifththeeadadtaatna.,yy.c,ccaannebbee mmodoeleddbbeyyssplpeeccieiffyyidinnggththeessttruuctcurteuoofrf ZZe,, GGaannd dRR.. "7Tfhbeemmodoedell mats matrix ZZ iissddeessiiggnneedd nintthhee ssaammee ffaasshhiioonnaassXX,,tthheemmododeellmmaatt.ifixffoorr hetheffiixxeedd- effecs paramezer. effects pararr~ters. FFoorr tthhee mmaattrriicceessGG aanndd RR., aa ccoovvaarriiaannccee ssttrruuccttuurree msmust bbee sseelleecctteedd iinn uussiinngg mmiixxeedd models. models. Since Since oobbsseerrvvaattiioonnss on on diferent different subjects subjects ars ar~ assumed assumed tto be be iinnddeeppeennddeennst,, the the srucre structure refers refers tothe to cthoevcaorviaraiannccee paiemofrepeated pattern of repeated mmeeaassuurreemmeennttss on on the the same same subject. subject.. For For most most ofthesestructures, of these structures, ththe covariance covariance between between two two oobbsseerrvvaattiioonnss on on hethe same. same ssuubbjjeecctt ddeeppeennddss cnly only on on the the length length ofthe of the time time iinntteerrvvaall bbeettwweeeenn mmeeaassuurreemmeennitss and and the the vvaarriiaaanccee is is ccoonnssttaanntt ove over ime. time. NNuummeerroouuss ccoovvaarriiaanncceesstUrrcutctuueressexeixsistt.. CCoommmmoonn eexxaammpplleess includethe include the ffoolllloowwiinngg.. SSiimmpplleecocovavrairiaannccee ssttrruuccttuurree ((SSIIMMD)ssppeceicfifiieesstthhtattthhee bosbesrevrvaartiioonnss aeare iinnddeeppeennddeenntt,, even even on on the the same same ssuubbjjeecctt,, and and hav have hhoommooggeenneeoouuss variance. variance. Tis It is uussuuaallllyy not not realsic realistic for for most most rreeppeesatteedd measures measures data data because becaus~ it it ssppeecciiffiieess hat that Gbservaions on the same subjectaeindependent. Compound symmetic (CS, therwise observations on the same subject are.independent. Compound symmetric (CS, otherwise 11779999..00001100 3M _MMNN0o22448822117722 3P3aMMgCeCoiomlmpoparanenysy P~$e [ ! of 63 , Kk~noownwaanss vvaarriiaannccee ccoommppoonneennttss)) ssttrruuccttuurree ssppeecciiffiieess tthhaatt oobsbersvateionrsoovnntathhestsaaimmeeossuubnbjjeescctt hhaavvee hhoommooggeenneeoouuss ccoovvaarriiaannccee aanndd hhoommooggeenneeoouuss.,vavarriiaannccee.. CCoorrrreellaattiioonnss bbeettwweeeenn ~twoo oobbsseerrvvaattiioonnss aarree eeqquuaall ffoorr aalll ppaaiirssooff cobbsseerrvvaattiioonnss oonn tthhee ssaammee ssuubbjjeecctt.. AAuuttoorree~grreessssiivvee oorrddeerr I1 ((AA.RR((Ll))))ccoovvaarriiaannccee sstrruuectturree ssppeecciiffiieess hhoommooggeenneeoouuss vvaarriiaannccee bbuutt tthhaatt ccoovvaarriiaanncceess. bbeettwweeeenn oobbsseerrvvaattiioonnss oonn tthhee ssaammee ssuubbjjeecctt aarree nnoott eeqquuaall,, bbuutt ddeeccrreeaassee toowwaarrdd zzerroo ~wviitthh iinnccrreeaassiinngg tiimmee iinntteerrvvaall bbeettwweeeenn mmeeaassuurreemmeenntt~s ((llaagg)).. TItss lliimmiittaattiioonn iiss tthhaat oobbsseerrvvaattiioonnss oonn tthhee ssaammee ssuubbjjeecctt ffaarr asppaartt iinn ttiimmee wwoouullddbbe~ sesesnetnitiaallllyy iinnddeeppeennddeenntt.. AAuuttoorreeggrreessssiivvee wwiitthh rraannddoommefefffeecctt foorr ssuubbjjeecctt ((AARR ++ RREE)) ccoovvaarriiaannccee sstirruucemtrue~ ssppeecciiffiieess hoommooggeenneeoouuss vvaarriiaanncceepplluusstthhee ccoovvaarriiaannccee bbeettwweeeenn oobbsseervravtaitoinsoononns. tthheessaammeessuubjebctajairsieesesfcfrrotomm ttwwoo ssoouurrcceess::1I))aannyyttwwoooobbsseerrvvaattiioonnsssshhaarree aa ccoommmmoonn ccoonnttrriibbuuttiioonn bbecaeusectthheaeyyaaurrc~osonntethhee ssaammee ssuubbjjeecctt;; aanndd 22)) tthhee ccoovvaarriiaannccee bbeetcwweeeenn oobbsseerrvvaatiioonnss ddeeccrreeaasseess eexxppoonneennttiiaallllyy wviitthh llaagg bbuutt oonnllyy to tthhee ccoommmmoonn ccoonnttrriibbuuttiioonn ((nnoott ttoo iinnddeeppeennddeennccee)).. TTooeepplliittzz (('TrOOEEPP)) sstrruuectturree ssppeecciiffiieess tthhaatt ccoovvaarriiaanncce ddeeppeennddss oonllyy oonn llaagg bbuutt nnoott aass a mmaatthheemmaattiiccaall ffuunnccttiioonn wwiitthh a ssmmaallll nnumuberomoffppabarraamemeetteerrrss.. TThhee u'unnsstUr'uuccttuurreedd' ssttrruuccttuurree ((UUNN)) ssppeecciiffiieess nnoo ppaatttteerrnnss iinn tthhee ccoovvaarriiaannccee mmaattriixx aanndd iissththeerreeffoorree ccoommppleletteellyy ggeenneerraall.. TThhee aabboovvee sstrruuccttuurreess aarree aapppprroopprriiaatt~e iiff eeqquuaall ssppaacciinngg ((ooffddataata)) iis aassssuumm~ecdl iinn a ttiimmee sseerriieess aannaallyysseess.. In sivations where unequally spaced longitudinal measurements exist, spatial covariance In situations where unequally spaced longitudinal measurements exist, spatial covaxiance structures can be used. In the present analyses, equal spacing was assumed given there structm-es can be used. In the present analyses, equal spacing was assumed ~ven there w~,e'erree aapppprrooxxiimmaatteellyy33 yyeeaarrss bbeettwweeeenn eeaacchh mmeeddiiccaall ssuurrvveeiillllaannccee pprrooggrraamm eexxaammiinnaattiioonnss. Akaike' information criterion (AIC) and Schwarz' Bayesian criterion (SBC) are Akaike's inform,at.ion criterion (AIC) and Schwarz's Bayesian criterion (SBC) are iinnddiicceessooff rreellaattiivvee ggooooddnnesess-so-of-f-ffiitt tht that were were usedto used to compare compare models models with with the the same same fixed fixed effects, but different covariance structures. SBC penalizes models more severely forthe effects, but different covariance structures. SBC penalizes models more severely for the 1177999..00001111 3M_MNo2482173 3M MN02482173 P3MaMCgeoCm2opm0a0pan6ny3y Page 12 of 63 , nnuummbbeerrooffeessttiimmaatteeddppaarraammeteteerrsstthhaannAAIICC aannddtthhuusstthheettwwoocrciritteerriiaa diidd nnoott aallwwaayyss aaggrreeee oonn tthhee cchhooiiccee ooff-"boeesstt' mmooddeell.. SSBBCC wwaass pprreeffeerrrreedd.. nthe present study. the continuous outcomes of lipid and hepatic clinical In the present study, the continuous outcomes of lipid and hepatic clinical cchheemmiissttrryy tests tests wweerr~e eevvaalluusatteedd ss as rreeppeeaatteedd mmeeaassuurreess iinnccoorproproartiantgitthnhege rraannddoomm ssuubbjjeecctt eeffffeectt ffiitteedd t1o aammiixxeedd mmooddeellbbyytthhee MMIIXXEEDDpprroocceedduurree iinn tthhee SSAASS ssttaattiissttiiccaall ppaacckkaaggee ((LLiittteelll eett aall 11999966).). RReessttrriicctteed mmaaxxiimmuumm lliikkeelliihhoooodd eessttiimmaatteess ((RREEMMLL))oofvf avrairiaannccee ppaarraammeetteerrss wweerr~e ccoommppuutteedd.. AAddjjuusstteedd rreeggrreessssiioonn mmooddeellss wweerree bbuulilkt bbyy iinnttrroodduucciinngg aallll ccoovvaardiaatteess ((sse bbeellooww)) aanndd tteessttiinngg tthhee ccoovvaarriiaanncce ssttrruuccttuurree. BBaasseedd oonn ggooooddnnesess-so-of-f-ffiitt tteessttss ddeessccrriibbeedd aabboovvee,, AARR++RREE,, wwaass rroouuttiinneellyy ccoonnssidiedreedrttehhede bbeesstt ccoovvaarriiaannccee ssttrruuccttuurree cchhoosseenn ffoorrtthhee mmiixxeedd mmooddeellss.. CCoovvaarriiaatteess iinncclluuddeedd PPFFOOSS ((oorr PPFFOOAAoorr TTOO)F),, yyeeaarrss ooff oobbsseerrvvaattiioonn,, tthhei-nitneterraaccttiioonn tteermmooff PPFFOOSS aanndd yyeeaarrns ooffobosbesrevrvaattiioonn,, aagge,, bbooddyy mmaassss iinnddeexx ((BBIMVIf)lS,, cciiggaarreetttes ssmmookkedppeerrddaayy,, aallccoohhooll ddrriinnkkss ppeerr ddaayy,,yyeeaarraatt ffiirrsstt eennttrryy aanndd bbaasseelliinnee. (x first observation) years worked. For hepasic clinical chemisiy tests, serum (at first observation) years worked. For h..c.patic clinical chemistry tests, serum ttrriiggllyycceerriiddees wwaass aallssoo ccoonnssiiddeerreedd aaccoovvarairiaattee ((OOllsseenn eett aall 220~01l2a)).. RREESSUULLTTSS PPrroovviiddeedd iinn TTaabbllee 11 aarr~sccrroosss.s-eseccttiioonna]l aannaallyysseess oofftthhee ssttuuddyy ssuubbjjeeccttss wwhhoo. ppaanrtiicciippaateedd iinn eeaacchhoofftthhee tthhreeeeyyeeaarrss ((11999944//9955,, 11999977 aanndd 22000000)) ssttrraattiiffiieedd bbyy Ilooccaattiioona.. AAss rreeppoorrtteedd pprreevviioouussllyy iinntthhee ccoommpplleette ccrroossss--sseeccttiioonnaall aannaallyysseess ooff tthhessee pprrooggrraammss ((OOllsseenn etal et al 11999988:: 11999999;; 22000011)),, AAnnttwweerrpp eemmppllooyyeeeess in in this this lloonnggiittuuddiinnaall iinnvveessttiiggaattiioonn wweerree yyoouunnggeerr,, hhaadd lloowweerr BBMMIIss aanndd ddrraannkk mmoorree aallccoohhoolliicc bbeevveerraaggeess tthhaann DDeeccaattuurr eemmppllooyyeeeess.. "TThheeyy aalssoo hhaadd ccoonnssiisstteennttllyy olowweerr ttrriiggllyycceerriiddee aanndd aallkkaalliinnee pphhoosspphhaattaassee lleevveellss aanndd hhiig~heert HHDDLL aanndd ttoottaall bbiilliirruubbiinn lleevveellss.. DDeceactatuurr eemmppllooyyeeeess,, oonn aavveerraaggee,, hhaadd sseerruumm PPFEOOSS levels levels 11779999..00001122 SW. 3M MMNN0022448822117744 3P3MaMgCeCo1omm3p0pa1an6n3yy Page 13 of 63 ( ththaattwwerereehihgighheerrbbyyaapppprorxoimxaitemlya00.t..55epplppmmyiinn eeaacchhcrcorossss--sseeccttiioonnaallaannalaylyssiiss.. SSiimmiillaarr ffiinnddiinnggss wweerree oobbsseerrvveedd ffoorr PPFFOOAA eexxcceepptt wwiitthh tthhee 11999977 ddaattaa wwhheerree tthhee ttwwoo ppooppuulalattiioonnss. hhaadd ccoommppaarraabbllee mmeeaann PPFFOOAA lleevveellss.. `PPrroovviiddeedd iinn tthee ffoolllloowwiinngg ttwwoo ttaabblleess aarree tthhee ccrroossss--sseeccttiioonnaall aannaallyysseess ffoor tthhee tthhrreeee ssuubbccoohhoorrtts bbyy llooccaattiioonn.. AAmmoonngg AAnnttwweerrpp eemmppllooyyeeeess ((TTaabbllee 22)),, eeaacchh oofftthhee tthhrreeee ssuubbccoohhoorrtts hhaadd lloowweerr mmeeaann sseerruumm PPFFOOSS lleevveellss iinn 22000000 tthhaann aait tthheeiirr yyeeaarr oofefnenttrryy wWhheerreeaass tthheerree wweerree nnoo ccoonnssiisstteenntt cchhaannggeess aaccrroossss ssuubbccoohhoorrtts wwiitthh PPFFOOAA.. AAmmoonngg tthhee tthhrreeee DDeeccaattuurr ssuubbccoohhoorrtts ((TTaabbllee 33)) mmeeaann BPFFOOSS vvaalluueess ddeecclliinneedd oovveerr ttiimmee bbuutt mean PPFFOOAA lleevveellss tteennddeedd mto iinnccrreeaassee.. PPrroovviiddeedd iinn ttaabblleess 44 tthhrroouugghh 3300 aarree tthhee mmiixxeedd mmooddeell ccooeeffffiicciieenntt eessttiimmaatteess,, ssttaannddaarrddeerrorrosrs,,pp-:vvaalluueess aanndd 99:55%% ccoonnffiiddeennccee iinntteerrvvaallss ffrroomm tteessttiinngg ppootteennttiiaall ddeetteerrmmiinnaannttss oofflilippiidd aanndd hheeppaatiicc cclliinniiccaall cchheemmiissttrryy cchhaannggee.. TThhee nnaattuurraall lloogg wwaass uusseedd ffoorr aallll ddeeppeennddeenntt vvaarriiaabblleess.. . T"Taabblleess 44 tthhrroouugghh 66 ccoonnttaaiinn tthhee aannaallyysseessffoorr cchhoolleesstteerrool,l. TThheerreewwaass nnoo cchhaannggee iinn cchhoolleesstteerrooll aassssoocciiaatteedd wwiitthh PPFFOOSS ((TTaabbllee 44)).. OOvevrearlall,l PPFFOOAA wwaass ppoossiittiivveellyy aassssoocciiaatteedd. wwiitthh cchhoolleesstteerrooll aass tthheemmaaiinneeffffeecctt ccooeeffffiicciieenntt wwaass ssiiggnniiffiiccaannttllyy ppoossiittiivvee but but is its interaction interaction wwiitthh ttiimmee ((yyeeaarrss vvaarriiaabbllee)) wwaass nneeggaattiivvee ((TTaabbllee )5).. PPrroovviiddeedd iinn TTaabblleess S5AA tthrroouugghh 55DD aarrce sseeppaarraattee aannaallyysseess ffoorr AAnnttwweerrpp ffoorraallll ssuubbjjeeccttss (('TTaabbllee S5AA)) aanndd bbyy eeaacchh ssuubbccoobhoorrtt.. TThhee PPFFOOAAaanndd cchhoolleesstteerrooll aassssoocciiaattiioonn aappppeeaarreedd ttoo pprriimmaarriillyy eressiiddee wwiitthh tthhee 2211 AAnnttwweerrpp eemmppllooyyeeeess iinn ssuubbccoohhoorr~s AA ((TTaabbllee 5SBB)).. TThhiiss ffiinnddiinngg ccaann aallssoo bb~e oobbsseerrvveedd iinn TTaabbllee 22 aass tthhee ssuubbccoohhoornt''s mmeeaann PPFFOOAA lleevveellss wweenntt ffrroomm 11..3322 ppppmm.. tto0 22..3377 ppppmm aanndd tthheenn ddeecclliinneedd ttoo 22.0066ppppmm aat tthheessaammeettiimmeeththeeiirrcchohloelsetseterroollvvaalluueessrroossee ffrroomm 220088 mm~dg L1t0o2/22266mdmg~/ddLLLttoo 222299 mmgg//ddLL.. TThheerme wweerree nnoo aassssoocciiaattiioonnss bbeettwweeeenn cchhoolleesstteerrooll aanndd PPFFOOAA oobbsseerrvveedd aammoonngg. 11779999..00001133 IM_MN02482175 3M MN02482175 E3MSCCooAmmppaa]nnyy . he D ec at ur employee p ap ul t io n (Table SE or vers h ee significant a ssc Pag~ 14 iaions of 63 the Decatur employee population (Table 5E) nor were then significant associations `bbeetwtweeeenn TTOOFF aanndd AAnnttwweerrpp oorr DDeeccaattuurr bbuutt wwhheenn tthhee ttwwoo ssiitteess wweerree ccoommbbiinneedd tthheerree wwaass aa Signiant osiive sociation becween TOF and cholestrol Tables , 6A and 68) significant positive association between TOF and cholesterol (Tables 6, 6A and 68). Ther wer osignifica: assctaions becween PROS,PFOA orTOF with HDL There were no significant associations between PFOS, PFOA or TOF with I-IDL ((TTaabblleess 77 tthhrroouugghh 99)).. BBMMI],, aallccoohhoolliicc ddrriinnk~s ppeerr ddaayy aanndd cciiggaarreettteess ssmmookkeeddppeerrddaayy wweerree the mot significant asians wih HDL. the mosTtgsliy~eifeirciadnetsawsseorceiantioonssigwniithfcIa-InDlyLassocined with PEOSover me when both Tri#ycerides were not significantly associated with PFOS over time when both Anerp snd Decatur populations wee examined ogee (Table 10) However, among Antwerp and Decatur populations were examined together (Table 10). However, among tihnee ccoommbbiinneedd AAnnttwweerrpp aannddDDeeccaattuurrppooppuullaaitoionnss,, PPFFOOAA wwaass ppoossitiivveelly aassssoocciiaatteedd wwiitthh igscrde (Table 11) as se with th igen ose cosfcient for he main triglycerides (Table 11) as seen with the significant positive coefficient for the main ffckofPFO and enon gnifcant posiv mai coffin of years and the negative effect of PFOA. and the nonsignificant positive main coefficient of years and the negative cofffoithen coefficient for their innetesrcacrtioonn ((PPFOFAOxAx yyeeasr)s)..Th sigan The significantmmaainn f effect oofe fPPFFOOAA was the consequence of he Antwerp population (Table L1A) and primary subcohort A was the consequence of the Antwerp population (Table 11A) and primarily s~bcohort A (able 18) and 10a serexcnt subcohort B (Table 11. but no subeobors C (Table (table 1 IB) and, to a lesser extent subcohort B (Table 11C), but not subcohort C (Table 11D). Therefore, easton appeared be relied tthe Anwerp workers who 11D). Therefore, the association appeared to be related to the Antwerp workers who wweerte, rll enrolled iinn thhiiss nlognigtiutucdiinnaall ccoohhorrt bbeeggiinnniinngg nin 11999955,, bbuutt nnott 11595977.. TThheerree wwass nooxt a sigan assoiaon between PFOA and igycries among Decatur rkers Table a significant association between PFOA and triglycerides a~.ong Decatur workers (Table 115) Among the Antwerp subcohortA,thee mean glcerds eels ose fom 85 11E). Among the Antwerp subcohort A, their mean triglycerid~ levels rose from 85 ng 10 113 mg/L 0173 ml.a the same time te PFOA Ives ncresed from m13#2dpLmto1101253m7~pdpLmtosn1d23thmen~ddedcLliant ethde1s0a2m.0e6 ptimpme.theAilr PtFhOoAuglheehvemlsaiinncfrefaescedofrroTmOF 1.32 ppm to 2.3"~ ppm and then declined to 2.06 ppm. Although the main effect for TOF as significantly pose, th interaction tr ith im (yes) was ok significant was significantly positive, the interaction term with time (years) was not significant ((TTaabbllee 1122)).. AAggaaiinn.. tthhiiss aassssoocciiaattiioonn wwaass mmoorree ccoonnssiisstteenntt ffoorr AAnnttwweerrpp eemmppllooyyeeeess ((TTaabbllee: ' 1122A)) tthhaannDDeceactauturr eemmppllooyyeeeess ((TTaabbllee 11228B)),. ( 11779999..00001144 aw ozug2176 3M MN02482176 P33aMMgeCCo1omm3p0pa0an6ny5y A`Ammoonngg tthhee hheeppaattiicc cclliinniiccaall cchheemmisisttrryy tteesstts tthhaatt ~wveerree aaddjjuusstteedd ffoorrtthhee vvaarriioouuss cchhaanrgtiinngg ddeemmooggrraapphhiicc ffaaccttoorrssaannddtur'iiggll~y,cceerriidde lleevveellss,, tthheerree wweerree nnoo ssii~gniiffiiccaanntt aassssoocciiaattiioonnss bbeettwweeeenn PPFFOOSS,, PPFFOOAA aanndd TTOOFF wwiitthh cchhaannggeess iinn aallkkaalliinnee pphhoosspphhaattaassee ((TTaabblleess 1133.--151)5),, GGGGTT ((TTaabblleess 1166--1188)),, AASSTT ((TTaabblleess 1199--2211)),, AALLTT ((TTaabblleess 2222:-2244)),, otottaall bbiilliirruubbiinn ((TTaabblleess 2255 -2727))oor ddiirreecctt bbiilliirruubbiinn ((TTaabblleess 2288--3300).). OObbsseerrvvaattiioonnss aap0ppaarreenntt iinn "TTaabblleess 22 aanndd33 ccaann aalssoo bbee sseeeenn iinn tthheessee mmiixxeedd mmooddeell aannaallyysseess.. FFoorreexxaammppllee,,tthheettwwoo rmaoosstt ssiiggnniiffiiccaanntt pprreeddiiccttoorrssooffalaklkaalliinnee pphhoosspphhaattaassee wweerree riimmee ((yyeeaarrss)) aanndd llooccaattiioonn ((aass sseeeenn wwiitthh tthhee lloowweerr vvaalluueess aammoonngg AAnnttwweerrpp eemmppllooyyeeeess))..FFoorrAALLTT,, eennttrryy ppeerriioodd wwaass aallssoo ssiiggnniiffiiccaannttaas tit rreefflleecctteedd tthhee hhiigghheerr rreeffeerreennccee rraannggee vvaalluueess ffoorr AALLTT tthhaatt wweerree uusseedd iinn 11999944/9955 tthhaann iinn ssuubbsseeqquueenntt yyeeaarrss.. DDIISSCCUUSSSSIIOONN ( T`Thheessee aannaallyysseess wweerree tthhee ffiirsstt lloonnggiittuuddiinnaall aasssseessssmmeenntt oofftthhee fflluvoorr0occhheemmiiccaall mmeeddiiccaall ssuurrvveeiillllaannccee pprrooggrraamm aatt 33MM''ss AAnnttwweerrpp aannddDDeceacattuurrmmanaunfuafcatcuturirinngg ssiitteess.. `OOvveerraallll,. wwee oobbsseerrvveedd nnoo aassssoocciiaattiioonnss tthhaatt wweerree ccoonnssiisstteenntt wwiitthh tthhee ttooxxiiccoollooggiiccaall eevviiddeennccee that that PPFFOOSS pprroodduucceess aa hhyyppoolliippiidd~emmiic eeffffeecctt aat tthhrreesshhoolldd ddoossaaggeess iinn rraatss aanndd pprriimmaatteess ((33MM CCoommppaannyy 22000000;; HHaauugghhoomm aanndd SSppyyddeevvoolldd 11999922:: Ikeeddaacett aall 11998877:; PPaassttoooorr tetaall 11998877:; `SSeeaaccaatt eett aall 220000113a:: 22000011b:: SSoohhlleenniiuuss tet al al 11999933)).. OOuurrrreessuullttss ddiid ssuuggggeesstt a a ppoossiittiivvee aassssoocciiaatrioonn bbeettwweeeenn tteemmppoorraall cchhaannggeess iinn cchhoolleesstterrooll aanndd trriiggllyycceerriiddeess aanndd PPFFOOAA:; hHoowweevveerr tthiiss iiss aallssoo iinncoonnsisisstteenntt wwiitthh tthhee ttooxxiiccoolloog~icaall eevviiddeennccee tthhaatt PPFFOOAA mmaayy rreessuulltt iinn a a hhyyppoolliippiiddeemmiJcc eeffffeecctt iinn rraatss ((HHaauugghhoomm aanndd SSppyyddeevvoolldd 11999922:; PPaassttoooorr eett aall 11998877)) bbuutt pprroodduucceedd nnoo eeffffeecctt oonn bblloooodd lliippiiddss iinn pprriimmaatteess((BButueteanhhooffffeettaall 22000011)).. 11779999..00001155 33MM_MMNNo022448822117777 P~3aMMgeCCo1om6~p3[~a1nn6yy3 P~ge 16 ( EEvveenn tthhoouugghh wwee wweerree asbbllee ttoo p~errffoorrmm aa lloonng~ittuud~inna~l ~assseessssmmeenntt,, ~therree wweer~e sseevveer~all llii~mitatattioionnss 0to oouurr aanna~lyysseess.. WWee wweer~e llii~mitteedd ttoo 117755 eemmp~looyyeeeess ooff wwhhiicchhoonnllyy 4411 (24 percen) paricipated in all three surveillance years. Although agreater absolute (24. ~rcent) p~cipated in all thee su~eillance ye~. Although a veater absolute nnuummbbeerrooffDDececaattuurr eemmppllooyyeeeess ((bbuuttnnooktp~erncetn-tw.wiisse)) hhaavvee ppa~ritciicpipaattedd dduurriinngg eeaacchh yyeea~r,, for his longitudinal assessmentthereweremore Antwerp (57 percent) thanDecatur(43 for this lon~din~ ~ssment th~ we~ more An~e~ (57 ~rcent) ~an Decatur (43 ~perecnentt)) eemmppllooyyeeeess.. AAnnttwweer~p eemmppllooyyeeeess hhaavvee hhaadd lloowweerr sseer~umm PPFFOOSS lleevveell bbyy aapppprrooxxiimmaatteellyy 00..55 ppppmm ((OOllsseenn ~ett a~l 11999988;; OOllsseenn eett a~ l 11999999a;; 1199999%b;; 220~01la3;; 2001; 2~ib; 220~011c)).. T~heer~e wweer~e iinnssuuffffiicciieenntt nnuumm ber~s ooff ffeermuallee eemmppllooyyeeeess ffoorr nmyy m meagnainnignf~ull Tongitudinal analysis. Given the variability inherent in the analytical method (Hansen et lon~mdinM ~ysis. Given ~e v~ability inhe~nt in ~e ~ic~ me~ ~sen et 212001) and the different laboratories used, serum PFOS and PFOA levels may have ~ 2~1) ~d ~ ~ff~nt labo~tofies ~ se~m PFOS ~d PFOA l~vgls may have ssyysstteemmaattiicc em~oorriinnccoor~poor~atteedd iinn eeaacchh m me~asuu~rm emeenntt t~haat wwee wweer~e uunnaabbllee ttoo a~ssseessss ~as blood samples were analyzed only at the ime of the surveillnce program. This blo~ s~ples we~ m~yzed only at ~e time of ~e su~eillmce p~. ~is ( systematic eror may have masked associations with lipidorhepatic clinical chemistries, sys~mafic e~or may have m~ked ~s~iafions with lipid or hepatic clinical che~s~es, although the rangeofPFOS and PFOA measured was relatively consistent throughout the akhough ~e range of PFOS ~d PFOA me~md w~ ~lafively consistent ~mu~out ~e ssttuuddyy ttiimmee ~pedrioodd.. BBe~caauussee 33MM hha~s aannnnoouunncceedd aapphahs~ee-~ouutt ooff tthhee ppr~odduuccttiioonn ooff perfluorooctanyl chemistry-elsted materials, we doubt that there willbe manymore. pe~uo~tanyl h~mis~-related mater,s, we doubt ~at ~e~ will ~ many more subjects inthefuturethacan be included in this longitudinal assessment.Also,the subj~ in ~e ~m~ ~at cm ~ inclu~d in ~s Ion~m~n~ ~sessment. ~so, ~ findings from this assessment would suggest that serum PEOS levels have either. fin~n~ f~m ~is ~ssmen~ would suggest that ~mm PFOS levels have eider remained constantordeclined slightly over time among these 175 employees. On the ~m~ned constmt or ~lined slimily over time ~ong these 175 employees. On ~e otherhand.serum PFOA levels appearedto trend upwaonravdersag,e, by approximately o~er h~d. ~m PFOA levels appemd to trend upw~, on average, by epp~ximately 0.510 10 ppm for these employees. Another limitasion i the fac ha the serum PFOS 0.5 to 1.0 ppm for ~ese ~mp[oye~s. Ano~er li~tafion is ~e f~t that ~e se~m PFOS amndd PPFFOOAA lleevveellss mmeeas~uur~edd iinn these these employees employees were we~ lower lower than ~ those those tha that cause cause effets effec~ in in laboratory animals. la~to~ ~imals. 11779999..00001166 IM_MN02482178 3M MN02482178 P33aMMgeCCo7omm5p0paa6nn5yy Page 17 ~f63 (i IInnssumummarym,aalaloonngrgiittuuyddiin,naall aannaallyyssiiss oovveraeassirixxyyeeaarrttiimmeeppeerriioodd ooff 117755 AAnnttwweerrpp aanndd DDeeccaattuurr mmaallee eemmppllooyyeeeess ddiidd nnoott sshhooww ssiiggnniiffiiccaanntt cchhaannggeess,, ccoonnssiisstteenntt wwiitthh ttooxxiiccoollooggiiccaall ddaataa,, ooff lliippiiddoorr eheppiatcic cclliinniiccaall cchheemmisisttrryy vvaalluueess aassssoocciiaatteedd wwiitthh eeitthheerr PFOS or PFOA. The PFOS and PFOA serum levels measured in these employees were PFOS or PFOA. The PFOS and PFOA serum levels measured in these employees were lToowweerr tthhaann tthhoossee tthhaat ccaauussee eeffffeeccttss iinn llaabboorraattoorryy aanniimmaallss.. 11779999..00001177 IM_MN02482179 3M MN02482179 , RREEFFEERREENNCCEESS MP3aMgeCCo1om8mp0pa0an6ny3y Page lg of 63 3i3tMsMsaCCloso.mmppSatan.nyyPa((u22l0000(00V))I..N)SS:II3DDMSSCIIonnmiittpiiaaallnaayss,ssee(ssussnmmpeuenbntltirrseehppeoordrttr::ePPpoeerrrtff.lluuoorrooooccttaannee ssuullffoonniicc aacciidd aanndd M`itMsiinsnannleetasap.pooSlliti.ssP((aMMuNNl)-()~:UUrNin)vi:ve3reMsrsiittCyyooomffpMMaininnynn,ees(souolntapa,u, b((uluinnspphuuebdbllriiesshpheoedrdt)rr,eeppoorrtt)).. AP`eAnrndfdleeurrossrooonnoDDcJtJa,,nMMoauutlIevvaaannnada DPDeEErf((l11u9o99r9o77oa)c).t.anAAennsaaulllyyfttioicncaaaltleRReienppoHorurttmffaoornr tthSheeerDDueetmteebrrymmiLinnCaat/tiiMooSnn.ooffIthaca NNPYe:YrAf:lAduvdoarvoanonccceteaddnoBBiaiotoeaannaanalldyytPtiiceearalflluSSoeerrrovvoiicceeetassnIIennsccu;;lAfAouunggauutsesttin1199H997u7.m. an Serum by LC/MS. Ithaca APAennrddfeelrurssooornnooDDcJtIa,,nMMoauutlelvaavnnadaDnPDeEaErf((l11u99o9r97o76ob)c).t.anAAennsaualllyyfttoiinccaaailleRRieenppoHorurstmffaoonrr ttShheeerDDueemtteebrrymmiLinnaMattSiioo.nn ooffIthaca NPNYe~r:'f:AlAudodvrvaoanoncccteeaddnoBBaiiotoeaannaanaldlyytPtiicecaralflluSSoeerrrovvoiicceeetassnIIennsccu;;lfSSoeenppatteteemmibbneeHrr u11m9999a77n.. Serum by LC/MS. Ithaca BBLuiutdteeennrhhoPof.fffO.JllLLs,,eCnCoGossWtta.aGT,,hEEollcmcooommrbdbeeCPC.,,TFFoaasrrirrcaairrtDDy,,ofHHaaanmsmenonnKsKi,,ueImIwwanpaieiHrHf,l,ulJouurnnoggocRRt,a,nKKoaeetnnenne(dAeyPdGFGy,O,) in : LccyyienndooemmrooPllg.guOusslsmmeononnGkkWeeyy,ssTaahffotemrr f22o66rdwwePeee.kkTssooofxfoiocriratayl oddofossaiimnnggm.. o((ununinuppmuubblpliiessrhhfeleuddorrreoeppoooerrtta))noate (APFO) in HHquaaannnstsieetnnatKKiIvJ,e, CCchlleaemrmaecitnaerILi.AAz,a,tEEilolllneefofsfsooornngMMaEnE,i,cJJfolhuonorsoohcnhJJneIHm-iIOOsca((l2o2s0000i1nn1).)b.ioCClooomgmpicopauolnudmn-adtsr-pisecpceeisc.fiificEc,n,viron qSScuciianTTteeictcahhtnnivooell 3576-770. characterization 35:766-770. oF organic fluorochermeals in biological matrices. Environ { HHpeaaruuflgguhhooormomctBBa,,noSSippcyydadeceivvdool(lddPF0OOA((1)199,992p2)e).r.lTuTohhreeocmmteeaccnhheasananliispsmhmonuuinncddeearrclliyydiinn(ggPFtthhOeeShhAyy)ppooalnliidppecemlmoiifccibeefifffceeccatctioodff. pBeirofcluhoermoiectaaneotiBciaocpihdys(iPcFaOAAc)t,ape11rf2l8u:o6r5o-c7t2a.nesulphonie acid (PFOSA) and elofibric acid. Biochemica et Biophysica Acta 1128:65-72. clIkyketeddoaachTTr..oFFmuuekkPuu-dd4aa5KK0a,,nMMdoporeiilrIIo,,xEEinnsooommmeotoportMoMlo.i,fKKerooamtmiaoaini TTi,n, SSrauutgglaaivTTer((bt19y988p77e))r..flIIunnodrdiuurccatttiioeondn ooff eocodcycstttoa)anncNehesesruouwlmlffYooeonnriPikcc-:4aaS5icp0dird.ia.nngIIdnenr::peVPPreoeerrrxliii.asrvgooo,mssrpmaeepepss3r0iionn4l-iBBf3ei0or8ali.otigoyon.aainnlnddrMaoMetdleiigdvcieicrnyinebe.y.p((eIrH-f~lDuoFFraaihhnmratiiedaannddi HH SSiieess,, eds) New York:Springer Verlag, pp 304-308. JPJPoeoerhhrffnnllssuuoooonnrrooJJoo'DDcc,t,taaWWnnoooloaatlttteeeerraaJJnn'TIdd',, PPCCeeoocrllffaall.iuuizzooyyrrooOGooEFce,t,t,aaRRnneeeetssthuhuwlwliffoliollnnl aaPPttAAee,,iiNnnNeHHelulsusmmoonananRnRMMSS.ee.rruuQQmmuuaUaUnnsistiifinnfiiggccaaIIotoiinnoo--nnPPaooaififrr `EESxxptterrcaatccrttoiiomonentaarnnyddwiHHtiihgghhAuPPteeorrmffoaortrmemadannSccaeemLLpiliqqeuuiPiddreCCphahrrraootmmiaoatnt.ooggSrrtaa.ppPhhayyu--lTT,hhMeeNrrmm:oo3sspMprraEayynvMMaLasassbs, 1996. Stt~ctrometry with Automated Sample Preparation. St. Paul, I~-N:3M Env Lab, 1996. LaLinitatttleeylisliiRRsoCCf..rPPeeepnneddaeetrreggdaasmstet aJJ,,suNNraawetasarrdaaajjtaeann. RRSt((a22t000M000e))d.. MM1o9o:d1de7ol9lii3nn-gg18ec1oo9vv.aarriiaannccee ssrtruuecttuurree iinn tthhee analysis of' repeated measures data. Stat Meal 19:1793-1819. LLCiaitcr~eyellllNRRCCCS..AMMSilillIliinkkseteinntuGGtAe~,n,c.SS.tt.rroo1uu9pp96WW, W6W3,3, WWpoplo.flfiinnggeerr RRDD.. SSAASS SSyysstteemm ffoorr MMiixxeedd MMoodedlesl.s. Cary NC:SAS Institute Inc., 199(5, 633 pp. OcOllilssneeicnnalGGcWWh.e.mBiBsuutrrrrriiiesssJJ,'MMh,e, mMMataaonldoenglJyJH'dla-.In,ZedZoobhlbeoorllmLLenRRe((s11i99n998r8)e).l.atAAinonneeoppisiddeeermmuiimoolllooeggviiecclsiinnovvfeesstitgiagtiaotniooofnf cppCeleoirrnmffilplcuuaaoolnrrcoyohoo(eccumttanainpnseeutrbsisleuuislls,ffhoohennedaamttreeeaptiioonnrlDomm)ga.aylleeanfflduuoohrrooorccmhheoemmnieicscaailnl pprerrooladdtuuiocctntiiotoonnseeemmrpuplmlooyyleeeeveses.l.sSSottf.. PPaauull::33MM Company (unpublished report). 11779999..00001188 33MM_MMNNo022448822118800 P33aMMgeCCoo9mm0pp1aa6nn5yy Page 19 of 63 ( aOOlnlsdseehnnepGGaWWti,c, BBaunurdrrriilssipJJiMMd.c,lMMinaiancndadleelclhJJeHHm,i,sZZtoorbbyeeltlesLLtsRRi((n11f99l999u98o)ar.)o.chSSeeemrriuucmamlpppeerrroffldluuuocortrcioooocnctteaamnnpeelssouuylleffeoonsna.attee: JaJ'nOOdEEhMMep44a11t(i(c99))a:7n79d999-l-i5p80i06d6..clinical chemistry tests in fluorochemical production employees. MOOlalssneednnelGGWWJ,H, (LL1oo9gg9a9a5nn).PPWWF,,luSSoiirmmoppcsshooennmiCCcAaAl,, eHHxaapnnossseeunnreKKJaJ,s,sBBeuusrnsrm'iiessnJIt'MMo,,fBBDueurcrllaeetwwurMMcMhM,e,miSScccahhluuammpnpederfrttilJImCC,, MppllaaannnttdecermlaJpp'FllIooyy(1eee9es9s..9bSS)t.t.. FPPalauuuoll:r:3o3McMheCCmooimmcpapalanenxyyp((ouusnnupprueubballsiisssehhseesddmrreeepnpotortro)tf)..Decatur chemical and film OhOellpssaeetnnicGGeWWn,z,yBBmuuernsr'i,isscJIhMoMl,,eBsBtuurrrollleewwanMMdMMl,i,poMMparanondtdeeeilnlsJJ'HiHn ((a22m000m000o))n.. iPPullmaasspmemraaflccuhhooorlloeeocccyytssaitonockkaiintnenn aanndd pphrreoopddauutciccttiieoonnnzywwmoorerkkse,errcssh..oDDlerrsuuteggrCoClhhaeenmmdTTloipoxoxipiccrooollte22in33s(44-i)n6:60a03m3--m662o20n0.i.um perfluorooctanoate OOslelssreeunnm GOpeWWr,f,luBBouurrfolloeecwwtaMMnsMMu,l,foBBnuaarrtrdess(JJPMMF,O,SMM)aanandndedellpeJJr'HHif((u22o00r00o11o)ca.t).aAnAcoraoctsreoss-(ssP-esFceOtcAtii)oonnianallealaanntaaillyoynssisstoooff ccsfleleiirmnnuaiircclaaaellpec~cmhhrpfeellmmuoioiyssrectoreyoy,c,pttatahhrnyiysrcruoiolipfidaodhnnhtoaostrremomfo(PontnFheeeO,,2Shh0)ee0mma0anatdAtoonpllteoowrgglefyyruaaponnraoddnoduucDrrtiieanncnaaaollyytasstuieirss(fPrrleeFussOuoulrlAttossc)ffhirernomomrimeclmmaaaltailolmeeneaadtnniocddal fsseuumrrvvaeeliielllleaamnnccpeeloppyrroeoeggrrpaaammr.t.icSSipCt:aPPnatasuullof((MtVhNNe))2::0330MM0 CCAoonmmtwppaearnnpyya((nuudnnDppuuebbcllaiistsuhhreeddflurreeopprooordcr)th)..emical medical JOOKll.sseeMnnaGnGdWWe.l, SSJccHhhim(m2ii0cc0kl1dlbee)rr.MMNDNe.s.cTTriiieeprrt~einnvsse JJsMMu.m, mLLaoorggayaonnfPPsW We.r, uBBumurrrfrilissuoJJrMMo.c,hBBeumutirlcleaewlw lMMevMMe.l,sLLauumnnoddnbbgeerrgg `JepKemrmo,ppgMllrooayaymnee.edeeSppltaa.rJrtHtPiiacc(uii2plp0:aa03nntV1tss1bo)oC.ffottDmhhpeeesayycneeraiyaprrt(i22uv00ne00pu0s0ubAAlmninmstthwwaeeredyrrrppoefffpllosuve)oor.ruromocchhfeelmumoiicrcoaalclhmmeemeddiiicccaaalil lsseuuvrrevvleesiilalllmaannoccneeg program. St. Paul:3M Company (unpublished report). TOO2ll0ss0ee1nn)GG.WW.D,esLLcoorggiaapnntiPPveWW,s,uSSmiimmmapprssyoonnofsCCeAA,r,uBBmuurrruniossrJJoMMch,,eBBruuirrcllaeewlw llMVevMhe-,~ls, LLauumnnoddnbbgeerreggmpJJKlK,o,yMMeaeannddeell JJIH-I "`pP(pa'a2aur-rlt0:ti0ic31cicipM)pa.annCDttsoseomtospcfhratihepnetyiyyv(eeeuaansrrup22um00b0m0li00asrDDhyeeedcocafratetsupueorrrrutffml)lu.voofrlrouocochrhoeecmmhiicecamallicmmaeleddileiccvaaelllsssuuarrmvveeoiinlllglaanencmceeppplorroyoggerreaamm.. SStt Paul:3M Company (unpublished report). PaPsstautsdotiooeosrrToTfPP.a.mLLme~oeenKKiPPu.,mPPepererririlfM~luLAo~,r.,oGGoiciltllalineeossaPPtYel-((i11n99d88u77c).e).d hBBeiipooaccthheoemmmieicgcaaalllayannaddnmdmoproeprrhpoohxliooslgoomi~ecc.aall proliferation. Exp Mol Pathol 47:98-109. studies of ammonium perfluorooctanoate-induced proliferation. Exp Mol Pathol 47:98-109. hepatomegaly and peroxisome `SSSeeaaabcc-aactthrAAoMMni.c. TTdhiheootmmafrfyoortrddoxPPiJcL,itHHyaoanfnpssoeetnnaKKsJsJ,i, uCCmlleeprmeaeernnflLLvAAr,o,eCCtaaassneeesMMuTlT,f,oBBniuuctteaencnhidohfoiffJYLrfLat(2s2.000T01o18xa)i).c.ol SSSccuiib((-scsuhubrbommniiittcteedddie22t00a0r01yi3at)o)..xicity, of potassium peffluorooctanesulfonic acid in rats. Toxicol S{SoeevaaicccaaitrtyAAsMMt.u.diTTehhso0offnoorrpddefPPJlJ.'u,oHHraoanonscsieeannnKKsJsJu,',lOOflolssneeannteGpGoWWt,a,sCCsaiassueemsMMaTlT.t. BBinuutcteyennnhohomofofffJlJgLLu..s SSmuuobbncckhheroryonsin.cic: TTtoooxxxiiiccciootyll sSStccuiid((iessusubbommniipttteeed~d..u2o200ro001o1bcb)t).a.nesulfonate potassium salt in cynomolgus monkeys. SSPeoorhhfllleeunnoiiruuosscAcAtKKa.n,eEEsxruikklssfssooonnne AAsMMc,i, HiHooaggspsiotrrtoeomnmtCCi,n,dKKuiciemmrlolaafnnddpMMer,,oDDxiecsPPoiimeearrlrreefaJJyWWa(c(11i99d9933B))-..oxidaton PaaPnhnedadrfrloomuttaohhcreeoorrolsacccTtttoaiirnvvieiitciisoeeulsslfk7ko2nnn9ooi0wcw-nn9a5ctt.iood beis be affected a potent affected by peroxisome proliferators inducer of peroxisornal fatty by pcroxisome proliferators in mouse liver. acid B-oxidation in mouse liver. Pharmacol Toxicoi 72:90-93. 11779999..00001199 IM_MNo2482181 3M MN02482181 vos. I)F{).~ roa I)F(')A TorTOF noAge iI]MI Ase AIc(,hol scheYes Ilaselh]e Years Viked Worked Comes ('igaretles Goes Cl~oleslerol noI 1DL Tweides "rriglycerides Mme AIk Phos aor( ~( ;'1" astAS'I" arAIJI" Talis 'r.lal Ifiliruhi. Dealiobn I)ired lliliruhi. HIANEog1. pClisc CSheatrotne!rAisnaanld CyliMniecs CsnheomcioefDAisnotnswnofdSeDeerrcnapPHMOaSl,ePEFOlA,oTOyF, we l ~lllO~ll)lli~ O)ara~terislk-s and (:linical Ol~inislries of Ant~rp ~lld D~calur Male We Figted iTr ona Med Sovionc Exam ween 19475 0d 3060 Who I~ailicipat~ in Two or More Medical Surveilla.c~ ~x;ll,i,ations I]ctween 1994195 outs ew xm 191J4! 1905 I g97 2111XI AMeps SS)0_ DeMcae(aNoA)) MAawnwpN=SSS)D| DMeeeni=SSO MAamnen (0S0O MDarenurN=7S9D) Mean was ae am we x us te ue wm wh aw I.g7 SI ) I.gt~ . .~(~a_!_u,r.!N =J!)~. Mean 2.62= 1.7g . A.~!W~.!rD.(_I~.-~_.55.) ......l_)~.:~_!~ir (N = .'i_:'i) Mean SI) Me;In SD 1.42 1.2fi I.R5 I.M ^nlwer|~ (N=IOO) Mean SI) I. 16 1.07 I')ecatur (N = 75) .. Mea. SI) 1.67~' 1.39 Was atm ase we Wr aa wr as 1.08 1.53 1.9~~ 1.0fl 1.54 1.61 1.41 1.17 1.43 1.21 1.83" !.53 Bem at am a an ae an a ad am 1.4~t, 1.77 3.(~' 1.77 I.gX 1.4X 2.17 1.76 1.74 1.24 2.3-I~' 1.72 Woe a wow ew om ww 0 3(, {,.(, 43'~ 32 6.8 4.1'i 7.3 .18 7,8 47~ 7.0 Mw wr ow om ow mr a ow am me a 2~.~ 2.4 ~8.0'~ 232 2.4 29. I'= 4..3 24.7 2.1~ 2').0'l 4. I Wow mw er ww ww wwe I. I'~ I. I 0.3 0.9'l I.(1 O. I O. I I. I'l 1.0 (I. I 0.2 10 87 we ww sa we el oe mr ks I I J) S.7 211.4~ 7.1 7.0 5.2 I(|,0'1 6. I 9. I ft. I 20.Y 8.5 47 ww 4 WB ww 217 sw" ne on ~4'~ 11 Wwe wm I I I nw we ow 72 woos ae ow 37 xn won 2~ Ww ne ox 44 0% 04 0s 02 (I.Q 0204 02 aw (I.2 7 43 13 7) I ~ 2~ I I I 7 0.4 0.4 I0~' 219 43 2~~ 103~ 47 31= 49 03 0.2 I 13 122 27 24 ] I 0.2 0.(H sa 5 om us 202 wow 49" ms lOg ws 68 ona 23 xe 26 won 30 ow od 0.8I' of om 0. l)' 7 45 I i 53 15 I I 6 12 0.4 0.(!7 sow sow soon 5 woos om oa mw 214 a ws on uw 43 Wem om ow ws 181'~ EE g7'l wom sow wow 33" w cs ow 1m 26 wos nou wou 32 wo ew wm ow ow 0.6 a 0M of wes 01 om (}. 1 10 35 I0 112 20 27 8 15 0.2 0.04 5 220 53'~ 131 5g 25 24 23 1.0') 0. I~ 8 41 12 gO 14 19 7 I 1 (I.3 11.05 5 213 44 17g~" 74" 2() 25 32a ().~ 0, I II 411 I0 115 2 I 18 7 14 0.2 0.(}6 APCUS Mpedl pom a. p < .fl.S h. p < .01 r. i) < dpedl comomarsoci mycsoflemaceingsh. _ozsez182 3M_M N02482182 11779999..00002200 Take. CosScio pis of Mem ndSand rifSeu OS, FOR. TO. ton vi Tabh." 2. ('nl~.~-.";cctional A,alysb; o1 Mean lind Standard I.)c.vhaion olScrunl I'FOS, I'I"OA, 1"( )F. Demi Tarts nde (ticsTee Sgro of ArteMorl ies 41) I)nlographk: ('h;traclerislJc.~ still ('li,fical { 'ht~lllisll'ies o1" Three Suhcro,lXS of Antwerp Male I]nlldO~ecs (A, I| mid (") Pipl Tw BtMe Sora Eoin eee 195 208 Who I)illlicipated ill Two or Mol'C Medical .~l.lrveill;lllCe EX~lltlill;lliOlIS nelwel~n 1995 ;,rid ws em ww 19o5 1997 21}0tl AWE) NONE) AMZ) _CONEML_ AMZ) heey cove _A_.(_.N.~. 21_) .... !_l (N = 45) ........A,(.N_~.2_I)_. C (N = 34) A(N=21) II (N=451 (? (N = 34) Mew | Men Sb Men Sh Mew SO Men SD Mas SD Mem 5D Mean Mean SD Mean SD Mean SD os wom am am 26 mn wm i aw ma ow on 1.32 11.93 1.53. 11.87 1.211 1.31 11.87I' 0.7 I mon ew le a7 am ea a en mw eo 2.2R 11.61 2.(16a 1.04 1. I 7 1.37 1.38 0.94 or Am Am dee am ee om as ss ww 1.59 I1.91 2.41= 0.81 I.Sg 1.51 1.52 11.89 a Woeoow 7 aw sw 7 ow oe oe 7 ow oa 5 7 38= 6 42" 7 32~ 7 wi meow aw moa ow mow ww omy wow ou 2.8 2.O 24.3 3.4 25.5" 2.7 23.9 2.4 dy 03 ae es a2 2 er ex ra won ue 1.2 (1.7 1.7" t.3 1.2 I.I 0.8 11.6 Conti 474 8s 7s 1 6 8 4 8 ss 7 6 8 4 8 5 8 BaiecYan 99 43 He @ ow ar 31 40 09 a me wn 40 4.3 5.3 4.9 9.9 4.3 I 1.6 6.3 5.3 4.9 WCohees w Wa mw me ww Mm Be ar Ww me 226' S$ nom om os 0 om om % wom ou ow on 51 Tipe 85 0 momo Ns @ wa mes aso 9s ws os 115 Mme ew on ow @ we om os om ow us on 67 aan FE EE 25 I x os 0% nm owm 0s ow 1 om sox 9 oa 211 wx e+ wom ow ow ow on oom won wow 7 31 Tllibe 003 0x 00 ox wor oe do mm ar we wm 11.8 Diatiiotin 02 an 02 ow 01 ois 02 am or om or ow oom O. I 511 9 69 19 I(1 5 12 11.3 0.1i5 187 dR 1(14 69 22 26 30 0.8 11.2. 34 II 41 12 II " 7 13 11.4 ll.01l ~29 56 123 55 23 , 22 22 1.0 O.l 46 233=' 12 52 65 154 17 (~1 13 3If 5 25 II 25 11,3 1,0 0.03 (I. I 38 196 I I 52 95 105 14 58 25 19 9 23 13 21 1}.3 11.9 0.06 O. I 31 13 55 12 11 6 7 0.3 0.()6 aw_wozee218s 3M_MN02482183 11779999..00002211 veo MDW AmoMga"niWblCiel.aMaCciuwoB terrsne:SedcNtiaaTSonnDeosd!ltAecAMrdooiaNrCemfhSv eMmeMSiEedsaiahen)aseaSode STrCMhaevdweeNoecSnon I=ErvxaoSme i)sinDaotfoiDofinm eSsActMrtoewnMM ePaenRlOeS1SE) 29,Dn5s4PpsFiOnyABMc,ia0eNwsT0n(O04E,,e1)S1oDd C)sMCeawd)onSeOoSN I'F(IS Table 3. ('ross-,~ol:liOllal A,ialysi,~ of Mean ;llid SI;itRl:lrd I)eviation of Scrum I'1~O,";, Pf;OA, TOF, I )en~q~raphic Characlcrislics and Clinical Clmmistries of Three SubgroLil)S of Decatur Male E,nl)h)yees (A, B and Who I'articipaled in Two or Mol~ Medical ~urvoillance Examinalions Between 1994 and 1994 :, 1997 2(100 __ A_ (_N. ~_~(.1) ........B_(N = 2111 _ A .(N =.201 _ C (N = 35) A (N = 20) P, (N = 20) Mean SI) Mean SD Mean SD Mean SD Mean SD Mean SD 2.07 I .(,7 3. I 3= 1.76 1.93 I.'/6 1.811 1.59 1.78 2.14 1.84 I.O3 c (N = 35) Mean SD 1.51 0.98 won mA LM Le WB le M20 ede PFOA 1.50 {I.~7 2.30= I. 14 1.41 I. 16 1.41 : 1.20 1.46 1.34 2.60~ 2.112 1.60 1,14 Tor 0s ee 4m am um aw mo 26 2m 2m im am aw TOF 2.37 1.54 3.64~ !.79 2.22 1.78 ~.14 1.78 2.16 2.16 2.9R 1.76 2.(1~ 1.32 ne @ 1 Ms ow 7 oe aw 1 ows ows Age 42 7 44 S 45 7 42 8 48 7 511 5 45 8 wa Wa ow WW a me 4s me a Wan ma as BMI 28.2 4.0 27.7 ~.3 28.3 4. I 29,6 4.5 28.9 4. I 28.7 3.3 29.3 4.5 mika 01 01 we ee ar me a2 a0 a ez oa wm me I)rinks/day O. I (I.~ 0.4 0.8 (1.1 ILl ILl 0.2 O.11 ILl 11.2 0.3 (I. I 0.2 Cowes 60 W040 su 3m ws 40 Cigarelle~day 6 13 14 15 ,I 10 5 I I 3 8 I11 15 aves 90 6. MA S2 We xe m2 We be 86 23 52 we mo Baseline Years 19.6 K6 Vocs Wo~ed 21.3 5.2 19.(; g.6 2(|.2 10.() 19.6 8.6 21.3 5.2 211.2 IO.O Qoesewt 3% WW % mw me wm ow wom a Cholesterol 235" 34 21H 36 223 3 I 208 37 228 39 199I' 33 212 4 I ou wow wow uw 9 em woos HDL 47~ 16 Tks 0 8m Ws Wns mow mm wo % ws om T~glycCride~ 180 8~ 39 9 229 145 45 I I IB8 115 41 9 178 " 112 47 12 .':18= 6 45 9 193 124 187 76 165 128 Mite mm wm ow ow om wm ow wm mom now ow AIk Plltls 98 29 1117 24 85 22 87 Ig 711 27 1~2 17 72 211 ar a x = om o o% ow ow wm wou on ow ow (;GT 41 25 52 22 35 36 31 20 29 16 34 2.t 27 17 st 2s 0m 6 x a om x om x om 4 3 1 AST 32 15 29 6 25 6 27 8 ~Z6 8 25 4 25 7 nr sm 0 om wos x 6% wo uo ow ALT 52 Todliiakn 06 02 05 02 oe 02 0s a2 0s 2 01 or on 02 Total Ililirubia 0.6 c7iWannt 0m7 it00e5 r 02 0Mne Wo01man0k0 70m1 Mm6m"oi 0m a1 oor a1 om Direct Igillrubin (I.2= 33 0.2 (~.115 47 11 30 15 34 - 16 0.5 0.2 (I,fi 0.2 11,6 0.i IL2 0.~ 0. I 0,04 O. 1 11.05 30 0.8 O. 1 18 32 0.2 0.7 0.08 0. I 11 33 0.2~ 0.8 0.04 (I. 1 14 0.~ 0.06 amw o2eez184 3M_M N02482184 11779999..00002222 Tae 4 in Cen sine, Sd rs 5, -Yl sd95% Conre Lins 'l'abl~ 4. Mixed M~dl Co~fl'icicnl I.'.'Slhnal~s, ~landard Errors {SF.), P-Valu~ and 9.5% Confidence Limi|s TorTein Pac Dkmp ofCoatCage ong EOSmd mrs wih I'rOnl "l'csting Polcntial Determinants of Chol.qterol* Change Including PFOS and the [ntcr'-,ction with mt oom of oto an elkEmp biumher of Years o1" Observation o[ Antwerp and Decatur Male Emp|oyccs Pod --C ----on 9955%f % Coi nfidd enceLe Liimmitin tss _c_e_ ...a..s..............e.e...CK_o_c(.~fl'fliccieiilt en_____ SS!E~. J as om Inteacep! 4.868 O. 12'7 ros uo os PFOS O.(llO VonOharviin oi ous Years Obwerv:,tion 0.(1009 0.005 PROS Vemone tos oz PFOS x Years Obs - O.~H 0.1~)2 re aun os Age O.(fi7 O.$)3 a oa ours BMI 0.(~6 ().(~13 Dray one onz Dfink~day 0.014 0.012 Chetty oom oon Cigaretle~day - 0.~9 0.(~ I <ape.l~i-vwaltele. <~.0001 18 ".84 n.83 o.0 ! o.07 =n.27 @.41 lLoowweerr wan4.618 om- 0.005 om - 0.008 oa- 0.0O4 aon0.002 "omes - 0.0005 "oon- 0.01 ! oon- 0.003 UpUpj2e1~rr ,. ss5.118 ams0.025 aoe|1.010 oan0.003 aos0.013 ous0.013 ans0.038 aon0.001 Lo~caatti~iomn* 000.3(1344 0o.0m37 3.366 [-- ao ous Lm ~l~ Peri~)tl** 0.(164 0.028 .02 Bute vers oom aos Baseline Years - 0.~ 0,003 .20 TU initirierismre sesseese rr-------------- tg *natural log "Ehsreyp)n *Antw~ vs Decatur ** 1994195 vs 1997 0- 0..003099 0O.. 110088 oo an 0.009 0.119 oom oon - 0.009 0.002 i----------eeSt-- swmczizes 3M_MN02482185 11779999..00002233 prCoemndy "'rTaahbloleem 55..TMeMisniixneegddPMMeontd~eilellsCCDooeefefficeiiec,rIiEmeslnihonftnaCelehe,s,eSSnsalant.tndedasarnrdCFEhroraorrnss ((ISSnEE)c},,hPPi-n-VgVaaPlulFesOs Aanndadd9955h%%eCCoInnotfneifridadceetnnicco~en wLLiiilm,nhiitlss from Testing Numbeorf Yeof aOfscrrvatsion of Antwesrndp DecaturMaleEmployees I)olential D~terminanls of Cholesterol' Change Including PFOA and the Inlet'action with Nnmber of Years of Ohsm'valion of Antwerp and Decatur Male Employees 95% ConfidenceLimits 95% Confidence Limila merce InlorcepI oo Cutien LS ............... .L.',..m.I_".fci__i_e!~I...... SI~. am om ~1.812 O. 127 pie Lower Upper p-v:due Soon asa S061 < .{X}O! Lower 4.561 Upper 5.063 Pron om om os oon oost PFOA Years Oscrvtion 0005. oms un "oom ou Years Ohserv~ilion ().O32 ILIX|5 0.0{F) : O.(X)5 .0~R~8 .24 0.013 - 0.004 0.0.5 I 0.014 PROAs Yet 0005 oo PFOA x Year~ Ohs - 0.005 0.~12 0s.005 00- 0.009 --00.00e022 Ase Age Ba BM! ves oon on 0002 oon O.008 on oon ou 000004 oon O.(l~i7 0.003 0.003 .007 .049 0.002 0.00004 0.013 0.013 Dinkekey ou oon Drinkshlay Cigmetesisy ~oo0r oon CilPtrelles/d:ty 0.014 - 0.01) I 0.012 0.(X| I 0 -o010 oor .263 -0003 oon .32 - 0.010 - 0.003 0.037 0.001 Locaicat oon [rd l..,Ocalion* O.(H ! (I.037 n oan ons .27 - 0.032 O. 114 Boy ero oes oon Entry Period** 0.068 0.027 o oars om .01 0.015 O. 122 Basen Years 0001 oom Baseline Years Worked _ Worked - 0.004 O.LR)3 as 000 oor .15 - 0.009 0.001 "*A*"nnAanaitntututorwrwaaulelerlslporovggv,psvseDD1ee5cc9aa7ttuurr *'1994/95 vs 1997 _mozsc2188 3M_M N02482186 11779999..00002244 "Tle SA. MidModeCoffe time, Sand Ss (SE, Vals nd 95%ConfiLeicnes 'r-hie 5A. Mixed Model Coefficient F.stimates, Standard Errors {Sff-), P-Values and 95% Confidence Limits To TestaPon Decminans of Ces Chnge locoPRO andteTrion I'ronl Testing Polcnlial Determinants of Cholesterol~ Change Including PFOA and the lnteraclion ih Number of YeasofOvation of Awe Mal Enpoyet with Number of Yca,~ of Observation of Antwerp Male Employees rene ere Coeamno lnterccpI Pron am PFOA Yorsomeran ous Yearn Ohscrvation OA Yamow oun PFOA x Ycm~ Obs C,~fl~cicn! 4.7 l0 0.029 O.(g)5 - 0.(~13 neAge oarBM[ Dinky D~nk~y Gpsrtiny Ciga~tle~day BayPaes ~lry Peri~al** Buel Yeas B~elin Years Woh Work~ wn0.~ ow0.~g om0.022 own O.{XX)7 om0.0~9 oom - 0.(~2 wpa SF. oi <oor 0.149 wore o 0,012 oom PF 0.(~6 oun 0.{~)3 oun on 0.~3 ows u 0.{~5 oon 0.013 oun OAX~2 ous o 0:038 ao7r a 0.~ p-value < '.~l .01 .36 .20 .~8 .14 .09 .70 .(H .67 ovCmdemctms 93% Confidence Limits Lowe upp Lower Upper an S005 4.414 ao ass 0.~ 0.053 om oor - 0.~ oom oan - 0.~9 ao o0te 0.~3, oom oo - 0.~3 ome oon - 0.~ 0.017 0.~2 0.016 0.019 oom aor - 0.~3 0.~ oor wis 0.~ 0.1'53 -000 oan - 0.Ol0 0.007 re "~nnaatluurmalllloogg. - **19~/95 vs 1997 woes 3M_MN02482187 11779999..00002255 "ble 1. Mixed ide Coeticen Fics, Sandiors (SE, P-Vlu nd95% Confidence Limi rd Table 5B. Mixed Model Coefficient Estimates, St=mdard Errors (SE), P-Values and 95% Confidence Limits roTeng Pct DermatofChurChange ncocding PROA aodthe traction wih fro,n Testing Polential Determinants of Cholesterol~ Change Including PFOA and the Interaction with NanberofYearsofOirvaion of Aner Sub A (1995, 199 nd 2000) ieEmployees Nt,mber of Years of Observation o1' Anlwerp Subgrm,p A ( 1995, 1997 and 2000) Male Employees 98% Confgece imis____ 95'$ Confidence Limits j Company Page 26 of 63 = lniercepl pron PFOA Yeu Observation Years Observation PROAXYewsObs PFOA x Yenrs Obs ae Age i Dinky Ddnks/,t~,y r-- Cigarettes/day Bseie Yeas Baseline Yeat~ Worked Worked Coen C~efficient som5.059 oon0.044 00370.037 001) - 0.013 oo- 0.0007 am0.~4 ase - 0.(116 aos (1.003 ons 0.015 SESE oan0.414 oon ().t)2t) outs0.015 00s0.005 oo0.012 oon0.012 ao 0.019 i ows (1.(XI5 aoe 0.016 pe p-value <ooor < .0001 on.03 .02 @.02 5s.95 n.77 ".41 st.5 i 3.36 Lows Lower a 4. ! 94 oom0.004 oon 0.007 00- 0.023 om - 0.025 oo - 0.020 -o0ss - 0.054 0007 - 0.007 oom - 0.018 Oper Upper sons 5.925 wos0.084 oor 0.067 002 - 0.002 ous 0.024 as 0.028 oom 0.023 0013 0.0 ! 3 000 0.047 tut og ~natural log aw mozeez168 3M_MN02482188 11779999..00002266 ae "Tlieo5,TesMtiinngedPMoodeell CDoeeftiecriemoniftCnehoa,ineSetaronsd ons (SF, P-Values and 95% Confidence ini Table 5(:. Mixed Mudl Cocfl'icicnt I~timales, Slandard EiTors (S]~), P-Values and 95% Confidence Limils l Change includingPROA and he licracion with I'rom Tcsling Polenlial Dclerminanls of Choleslerol~' Change Including PFOA and the lnleraclion wilh Numberof Year ofOvation ofAntwerp Subon B (199 0d2000) Mis pipes Number of Years of Observation of Antwerp Subgroup B (1995 and 2000) Male Employees oveComnenciins 95% Conlidcnc~ Limits i CooficSeE n phe Low Ue (2~fl~cienl SI.." p-value Lower Upper = ass 024 <oo0 a6 300 Interccpl 4.838 0.244 < 0.001 4.34fi 5.330 pron ors oor = -oois ous PFOA " ' 0.018 0.017 .30 - O.0 i 6 0.052 YeasOberon 0005 ous 5 -oon oon Years Obscrvalion (1.005 0,008 .55 - 0.0 ! 1 0.021 POA Yeon 0002 oom 0009 000s PFOA x Ye,'~rs Obs - 0.002 0.004 .58 - 0,009 0.005 ae anos ams " 000s oars Ag 0.(XH 0.{X)5 .40 - 0.006 0.015 ma oon om n oom oon BM! 0.014 O./X)9 .13 - 0.004 0.03 I Dinky oon oon as ous oor Drinks/day 0.O I 7 0.022 .45 - 0.028 0.061 re-- our oo " 000s oun Ciga~elle~dqy 11.002 0.003 .44 - 0.004 0.009 T BaselinB e Years rmammarms----ome-----------------oon--------oo-- n -- Ba~eliue Years Worked - 0.11001 0,006 .99 - 0.011 0.01 I raul 'natural log aw moz4e2188 3M_MN02482189 11779999..00002277 "Tle SO. Misc Mode Coxicicn mse,Stand Fron (5,P-Vlos1d 95% Confidence Lis Ts Table 5D. Mixed Model Coefficieni Hstimates, Standard ~rrors (SE), P-Values and 95% Confidence Limils om Teng Peat DekergatsofCholestrold Carpe Including PFOA edhe nein wih from Tesling Potential Delerminaals .f Cholesterolu Change Including PFOA and Ih Interaction with NaifYous ofOtervoaf AiwoenSuro C (191d2000) Mil Employes Number of Years ofObservali.n of Anlwe~p Subgroup C (1997 and 2000) Male Employees 95%Contre imi 95% Confidence Limits oo comdew Se phe lee Ue C~x.'fficient SH p-wdue Lower Upper Inert sm oan <a ass S100 lnlercepl roa * oan ww P ons om PFOA YonObernion -0010 om ~0s6s oom Ycam Obscrv-tion PoAxvamow 000 om o -oms ouss PPOA x Years Obs a aos om a ome ou Ag~ ma own oon o ais om BMI 4.528 0.004 - 0.010 O.OI0 0.016 0.009 0.28 I 0.062 0.026 0.022 0.006 0.012 < .0001 .95 .70 65 .01 .43 3.955 - 0.125 - 0.065 - 0.035 0.004 - 0.015 5.100 0.132 0.044 0.055 0.028 0.033 Drikatey oom am Fl om aio Drinks/d-y pssst "ooo oun = ow 00s Cigareltes/day 0,033 - 0.0001 0.032 0.003 31 -0.033 0.100 .97 - 0.007 0.006 w Bact Yous e ows .I om oon Baseline Yea~s ~~ Work - 0.005 0.008 .49 - 0.021 0.011 murs log | ~natural log w_wozue2190 3M_MN02482190 1177999..00002288 Tale. Mine ode Cocticen sic, Stand Eon (5, -Vlos nd 35% Confidence Limi Table 5E. Mixed Model Coefficienl Estimates, Slandard Errors (SE), P-Values and 95% Confidence Limits fmTsingPotcnil Determinants of ChkcterlChangs ocing PFOA and the ication wih from Testing Polcnlial Determinants of Cholesterol~ Change Including PFOA and the ]nteraclion wilh Numbeorf YeuofObservationofDecaturMak Employees Number of Years of Observation of Decatur Male Employees osobCmfemelimts 95% Confidence Limits i ern CofEiY dew 0S2E6 Intercqa von 006 one PFOA Coefl~cien! 5.220 0.016 S ft, 0.206 0.016 puke p-value <o01 ,~ .0001 Mo.34 lewLower 50 4.810 oon- 0.017 Upper Upper sao .5.630 oon 0.048 YanObservaion +0002 Years Obscrv,qion - 0.002 POA YenObs 0003 PFOA x Y~ms Obe - 0.003 re oo Age ma oom BM! Drinks oss Drinks/day Cpmeetiy oom Cigarettes/day Buy Peis ov Entry Period** Busco Yeas 002 Baseline Years BE rstes Worked 0.002 0.003 - 0.088 - 0.002 0.047 - 0.002 om mn -oon ours (I.(X)8 oon 2 0000 oon 0.003 ous x er oo 0.005 oom ss -o0ns oon 0.004 ous on ois -oois 0.035 aon 1s oom oo (1.001 os u oon ois 0.040 --o--o ----------@ --------0--010--------0--006---- ().1)04 .77 - 0.017 0.01:3 .22 - 0.009 .0.002 .70 - 0.008 0.012 .55 - 0.006 0.011 .01 - 0.158 - 0.018 . [ 5 - 0.004 0.0007 .24 - 0.032 O. 125 .62 - 0.010 0.006 ott og ~natural log "1953s 1997 *'1994/9.5 vs 1997 aw_o2ez191 3M_MN02482191 11779999..00002299 Tae. Table 6. from Mido PMot iCotint cs, SdEenSE F-A35%Cconfs Mixed Model Coefficie,! I~slimales, Standard Errors (SE), P-Values and 95% Confidence Krof Go olAhyreo s eitio aTn OkFEwdos os T~tiag Potential Detem)inanls of Cholesterol* Change Including TOF and the lnleraction LiteLimits with isos . Company P~g 30 of 63 Number of Years of Oh~rvalion or Anlwerp and Decalur Male Employees ec J as am Inlercepl CodfceSmH Ct~l'ficien! SI~. 4.828 0.127 or om om TOF 0.02 I Voronin 004 aos Year~ ObservaliOll O.O(H O.IX)5 pe p-value om< .l~01 =on.37 ---- 955%%CCoonfindenfceLiLiimmdiitssence ewe Lower asm4.577 ao0.006 ows- 0.t~)5 Ups som5.079 aos0.035 aone0.014 "TTOOFF xx YYeeaarrssObs. * -000,00033 00.000011 3: .007 -000.00055. 000.0000033. ~~ aon ous o oon ours Age 0.007 0.003 .0 I 0.002 0.013 a ao aos o oor oon BMI 0.006 0.003 .05 - 0.0001 0.013 Donny oon aon = oz ans Drinks/day 0.012 0.0 i 2 .32 - 0.012 0.036 Comets om aor n om oon Cigarettes/day - 0.001 O.(,q) I .37 - 0.003 0.00! Loaion aoe - 2 ons2 ans Location* 0.042 0.037 .26 - 0.032 0.115 [-- oss ou aon an Enlry Peri(~l** 0.063 0.027 .02 0.010 0.|!7 Bates ome aos on oz BWaosrekle iende Yeae ts e-s01}--04------------0.--003--------------.17---------------0.0-- 09 ------------0.0--02------ iArrrceoDe)s annaattuurraull lloogg . *Antwerp vs Decatur *'1994/95 vs 1997 swmcziez 3M_M N02482192 11779999..00003300 TTaubblreeo66mAAT,e. tiMisnixgeeddPoMMeooncdtakillCCDooe~stfeltircmiieinnntansI~tsitiomtfaCeteh,s.oSStta,an,elddaa"rdCBhEarrnrrogsres ((nSSIE~).),,dPP--VVaiTalluOueesFsnaaannndddgt99e55%%nCCoenoofnifciddoeennnccweeiLLthimiists fi'om Testing NumobfYeearr ofObcrvation Potential Det,~rminants of Cholesterol~ Number of Years of Observation of Aner Mole Employes Change Including TOP and the of Antwerp Male Employees Interaction with 95%Confidence Limits 95% Confidence Limits eo Cofelew Coefficienl Spe SI~. p-value lows Lower Umer Upper ree Intercept 108 TOF am oso <o001 aan sons 4.'/21 oon oon 2 -0004 oo 0.017 0.150 0.011 < .O001 .12 4.424 - 0.004 .5.018 0.038 Yours Observion 004 rd Years Obscrvalion O.t104 O.lXI7 5 -000 oon .55 - 0.009 0.017 TOFxYewsObs -00008 oo TOF x Years Obs - 0.0008 0.002 TM -oc0s oo .70 - 0.005 0.003 ABa 00000 00000s6 aoa -o00002z ooootm6 BMI Dinkatay oo ois " -o06 ots Drinks/day Cigetesiny 0000s. oon -0003 000s Cigarettes/day O.(X)9 0.009 0.019 0.0008 0.003 .0 i 0.006 .12 0.013 .14 0.002 '. .69 0.002 - 0.002 - 0.006 - 0.003 0.016 0.020 0.045 0.005 Bey Periods Entry Period** Belin Years Baseline Years Woded Worked "natura log ~naluml log "IUDvs 1997 **1~4/95 vs 1997 oon 0.070 "ooo - O,O(k)g oo o -0006 ous 0.038 oon0 5s 0009 0008 O.{X)4 .07 - 0.006 O. 145 .85 - 0.009 0.008 _o2ee2193 3M_MN02482193 11779999..00003311 bl 1. Mined Mil Coin art,Sand rors (SE), P-Vls1nd 95%Confidence Livi Table 6B. Mixed Model Cocfficien! l~limates, Slandard Errors (SE), P-Values and 95% Confidence Limits rom Teng Pena DekrmofiCvalnsrsl Chinge IcTiOFnsndghe ection with from 'l~sting Po!ential De.tcrminanls of Cholesterol~ Change Including TOF a~i the Interaction with Norra YousofOierovfDaeis oMinse Eploycs Number of Ye=n~ of Observation of Deca!ur Male Employe~a 95%Conitece Lin. 95% Confidence Limils Fn Company Page 32 of 63 -- co ....................... nerIntercept onTOP YanObvsion Years Observalion TORxYenob ]'OF x Years Obs aeAge BatBMI Drntasy Drinks/day Cmte Cigamues/day Buti Yeas Bl~eline Yem's J Worked rag Jnatural log per *'!994/95 vs 1997 Coelfiew _.(.'.~Im'__fi_c_e_!~! sau5.214 "oom0.014 0002 - 0.002 0m - 0.002 oon0.002 oun0.002 00m - 0.090 oo- 0.002 om- 0.002 SSEE om0.202 oon0.01 ! ooos0.008 oo0.0(12 oms0.005 wos0.004 : oms0.035 oan0.001 oom0.004 pee p-value aon < .000 I .19 .'/9 a.22 .69 ss.55 az.012 0.16 ! ".60 aanLloowweer 4.gl I om - 0.007 oom-0.018 ome 0.006 os - 0.008 ms -0.006 -oi0 -0.160 ou- 0.004 000 -0.010 UppUer pper sss5.616 oouosn0.013 omni0.001 oon0.012 oan0,01 l -aomsoe - 0.020 aos0.006 w_wozue2108 3M_M N02482194 11779999..00003322 PaeCs omey .i CUliillliny Page 33 of 63 Table 7. Mined Mase Coli: Emacs, Standard Fors (SE) P-Yaloesad 95% Confidene Lins Tal)lc 7. Mixed ldodcl Cocl'ficicn117.sli,ilales, Standard Errors (SE), P-Values and 95% Confidence Limits fromTingPotential Detrminantosf DL"ChangeInding PROSadthe neracion wilh from Testing Potential Determinants of HDL# Change Including PFOS and the Interaction with anesofYeas ofObservation of Antwerp snd DeMacleEmoploryes Number of Yc;u,'s of Obscrvatitm of Anlwerp and Dccntur Male Employees 95%Confidence Limits 95% Confidence Limits Costin (?oefficienl siSI~ patie Lower UUppppeerr [)-viihie Ttereep an oa <oon 39% aos lntercepl pros "ooo ooo a -o0 oor PFOS 4.212 " - 0.010 0.144 < .O001 .24 3.930 - 0.026 4.495 Year Otservaion 0002 woos a ~0008 oz Year~ Olisel'Vlil iilli 0.(1()2 .71 0.012 PROS AYews Obs 0001 oz 2 -000s 0002 o 0.005 0.00_.2 ree 001 00s 2 -00n oon Age II.(~ .22 - 0.002. 0.0! ! EY on oom <oo01 os 0010 BM! Drinkany ost oon <on oom oo Ddnk~day - 0.017 0.~ 0.013 < o00OI < - 0.025 0.037 0.010 0.090 Lr--" Cigarelte~day ot - O.{g~ oon0.~ I ows .0005 -00m - 0.007 -0002 - 0.002 Locaion EePros Efllry Perilldi* Bsc Yous webes Baseline Ycar~ Wo~ed ne*nAaantttumwuelrlIyoo~gva Decatur 99495 v3 *Antweq) vs 1991 ** t9~95 vs 1997 0006 ous 0.025 0007 - 0.~7 aon .89 [ La 0.032 .44 oon o 0.~3 .O3 "oom- 0.079 oss - 0.038 -oon3 - 0.013 oot 0.091 oss O.Og8 ~00005 - 0.0005 _Mo24g2195 3M_MN02482195 11779999..00003333 TTaublbetfe8r8.oo,mmMMTTiiexsxseeitddiNnnMgMgoooPPmddoeeeteerlnCCioteiofalflYilDDe'cfeaieicrttioseeenrrnomtmtfiiEEnnOsaastn,itltmtcssactoo,effr"s,HHvSSDDtLaoaaLnnfd'dtCAaCahnrihnadtanwoEEngegrrenrreooprIssncc((llSSuEiEdD))nie,,ncggPPaP--tPVuFVFaraOlOluMAoAeassakananndnEdddmthhp99ee55l%%oIInenCtCceaoroscnantfcfitdiidooeennrncwwcieeiLtthLhiimnists Number of Years of Ohservalilln of Aniwe,'p and Decatur Male Employees Comper Company Pats Page 34 of 63 = Inlercepl Ce Coen 12ocl'ficient__ 216 4.216 sn pve _.qF. ......~p-value ous <oo01 (). 1,15 ~,0001 95% Confidence Limits 95% Confidence Limits Lover Up Lower Upl~r 39 aso 3.929 4,.503 Poa PITOA "oom " - (1.006 aontl.(ll I 0 ..'i6 -o0m - 0.027 ons 0.0 Years Oerviion 000s aos Years Ollsl~rvllliun POA Yeon 0002 on Pl'q~li~. i ~Ciil-,,,l Ohg 11.011.5 - 0.002 I}.lltl$ I1.1102 3{35 ~- o0.s0u0s5 oon 0.014 " -000 0002 .40 - 0.006 0.002 re oon oon EY 00m oo Age 0.004 0.003 .28 - 0.003 0.010 aBM1 Drinking Drinks/day Cigreteiay Cigarelies/day Locaioat Localim~* EyProds Enlry Period** WBBaaesseeelliindnee Years Years WorEed "nao. ~natural lug *Antvery vs Deca *Antwerp ~sDe~alur "198495 v8 1991 *'1994/95 vs 1997 ~o0 ooo <oo01 - 0.017 [rs oun pr 0.tgl2 0.(104 0.013 < .0001 < .(RIO I "0004 . - 0.1}(H oun oo 11.1101 ~ .00(14 oo aon ss O.i~g 0.043 .g5 oom oom 5 0.02~ 0.032 .53 000o 7 ous T o - 0.007 0.003 .04 oom - 0.024 ook 0.036 "010 - 0.010 ons 0.088 ~oom oom - 0.007 - 00% 009 - 0.076 000 oom - 0.042 0.093 0.082 --o00n .01133 T -000.0000044 _Mo24s2196 3M_M N02482196 11779999..00003344 eoemasn "TTaabbllee r99..omMMTieixssetcidnMgMa~cPleeo!leCCnoaocelffifDcicieieeenntrtEEmsstiliin~mnaaattleoesfss,,HSSDalanLnddaCarhrddaEEnrrgreoorssI((nSSEEc)),,lPPu--TVVdOaaliuleanssnsgdannddth99e55I%%nCtCoenosfntifiiddneennwccieethLLiimmiitlss from `Niamber ofYeas of Otevain of Aver and Dect Male Esplayees Tesling Potential Determinants of HDL~ Change Including TOF and the Interaction Number of Years of Ohservation of Anlwerp and Decatur Male Employees with ooo MCoudemclmis 95% Confidence Limits Coen SE Coel'licienl __SL; phe p-value lLoowwer UmUpeperr Intercept aan ous <ooor 3s aso Intercept 4.217 0.14.S < .0001 3.931 4.502 Tor. TOP 0006 oo; " "00m 0010 "- 0.006 0.(xi8 : .44 - 0.023 0.0 i 0 YearsObscrvion Years Ohservalion TOPxYeurObs TOP x Yem's Obs AeAge aaBMI 0004 0.004 -usom - 0.(R)(F) 004 0.004 "oon - 0.O 17 [ 0.(XI5 oonO.(N)I oon O.(XL3 ooo 0.0(H a .47 El as.2.5 <oo0r < .000 I oor - 0.007 "oom- 0.004 oom - 0.003 -- o0.m02s5 oo 0.014 0002 0.002 0010 0.010 "- 00.00100 Dinkainy 00a on pr [rd 008 Drinks/day 0.063 0.01 ~ < .0001 0.037 0.089 Cetestiay oom oor Cigarelles/day - 0.004 0.001 005 -0007 .0005 - 0,007 0002 - 0.002 Locaions 07 oo Localion* 0.007 0.043 - -oom 002 .88 - 0.078 0.0'92 BatyPros oon oon oo os l~nlry Period** Baseline Vu on oun on -oon ~00001 Baseline Years 0 Woe Worked 0.021 - 0.(RI7 0.032 0.003 .50 - 0.041 0.084 - 0.013 - 0.0004 "~*nAnanatiuavraenlrllpoovggsDecatur "199455 ve 1997 *Antwerp vs Dc~:atur 3!. **1994/95 vs 1997 _ozse2197 3M_MN02482197 11779999..00003355 iceompsar Page 36 of 63 "TTaabbfrill~oeemm1I00T3..e~sMsMiilinnnixgge~dPNPMooMotlcuocdndtelieilamalColCDDfoeoYeeselcfaefrtrirmcisicinnntoaf!nOIl~bsctsloioimcfmlr"aTaFvilrt~etiegisg,,loynySnSccoactea~fnnnaddddAeaan~"rtsCdw~hEEeaarrrnsrnpooggrassced((IISnSnDIcE~eel).luc,cadPPit-in-nuVVggraalPiPluueFRsesOOslaSSanEnadnmdnpdd9l55ott%h%yeeeCeCInonsinoteefnrrifaiaddcceetinniooccnneewwL~iiLm tihhisls Numl~r of Years of Observation of AnI~=? and ~atur Male Employees 9955%% CConofnifiddeennccee LLiimmiittss ree lnlerccp! pros PFOS Cen SE Cocfficicn! 210 ons 2.730 ons aon O.1|25 0.335 0.(|2(! pe <o.o00o0n1 < 2 low Lower 20682.068 "ons -0.015 Ups Upper am 3.392 oss 0.065 Yours Years Oervaion Obsc~alion - 00..0(0~4 ons 0.O 13 PROS Yan 0006 ous PFOS x Years Obs 0.~6 n "om oa .73 - 0.029 0.02 I 2.22 --o00.00044 ois 0.015 AAgee oon0.(~3 oo0.~)8 @.~7 ~- o0.o0n111 ois 0.01g MBMiI 000.0(~6 oo0.~9 <oo01 ous < 0.048 oss 0.083 Drinksay ons am = 0094 os D~nk~day Cipmetesiny oan oon oo 000s oon Cigar~lle~day Locatont oz 009. 01 020 ~ati=~n* Bay rots ans om -00ss 02 FJ~I~ I~riod~* Bsc Years 00s oon = -oo10 oa Baseline Ymtrs J Worked - 0.029 0.011 0.052 0.089 0.(~15 0,033 0.~)3 0.0~D 0.073 0.~7 .37 .0002 .~0 ,50 - 0.094 0.005 - 0.143 - 0.055 - 0.010 0.035 0.017 0.247 0.234 0.019 ~"*"4nAAs1antanu9ttrrww9aalec4prl~o5y.gvvv5ssDD1ee9cc9aa1ttuurr ** 1994/95 vs 19~ _mozse2198 3M_MN02482198 11779999..00003366 _--Intercept PFOA I Lulill)a|iy rage 37 of 63 T Se L 'Fahle I I, Mixed Model Coefficiem [Lslimales, Standard Errors (SE), P-Values and 95% Confidence Limits LL fn)m Te.~ling Polential Determinants ofT,'iglyceride~ Change Including PFOA and the Interaction with blumbcr 0f Years of Observation of Antwerp and Decatur Male Employees -- 95% Confidence Limits eileen Coefficient t,;E p-value Lower Upper TT. 2..539 wm mw. 0.094 0,332 0.025 <!.0001 .0002 1.883 0.045 3.196 0.144 Years Ob~rvalion O.IX)7 0.012 .57 - 0.017 0.03 I ramon mm PPOA x Years Obs - 0.008 0.005 .12 - 0.018 0.002 - me cms on wm - Age BBMMII 0.006 00.006666. ,0.007 : 000.00099 ! .42 <<..00000011 - 0.009 000.04499. 0.021 00.008833 -- ww. Drinks/day - 0.027 0.032 .40 - 0.090 0.037 oP Cigarelles~day 0.011 0.003 " .0002 O.005 0.017 _------m am - Location* 0.072 0.0{)6 .46 - 0.118 0.262 mS Entry I~i-iod* * 0.1198 . O.070 .17 - 0,041 0,236 mma mm Baseline Years 0,003 0.007 167 - 0.011 0.017 Worke ed c-------------------------------------------- ah "naturallog ';4'|tJ94)tJ.s vs I~J'/ 3M_MN02482199 11779999..00003377 Tle 11A. Mixed Model Coefiin titsSida iors (SE), P-Vsnad95l%Coonficdensce Limits 'l'ahle 11A. Mixed Model Ceefficien! IL~!imales,!Slandard Errors (SE), P-Value~ and 95% Confidence Limits fro Towing Pte DetermofiTniagnetr!s ChangeInccing PFOAand he Inicrscion with fi-om Testing Potential Determinanls ofTriglyceride' Change Including PFOA and the Interaction with Numbeorf Yeof aOhirrvalson of Antwer Mle Employes Number of Ye.'u~ of Obse,'valion of Antwerp Male Employees 95%Confidence Limits 95% Confidence Limits ras p--ren lnlcrcept ProPFOA Yen Oeovtion Years Olk~rvali,m PROArYenObs PFOA x Y~ars Obs neAge aBMI Drinkstny Drinks/day Cipmecsny Cigarel~es/day Cafe Sw Coefficient 067 om 3.(167 "oo ow 0.089 -00402140 oooatns 0.024 Sl! 0.394 0.030 0.Ill 5 oniz{L012 ms O.I)39 om - 0.026 oon 1~.01R oom 0.1)09 oo0.014 ous0.033 oatsO.OOS pwp-value <a<..000 I os.005 ans.12 .22 wn.007 ".44 oon .0004 owLower 226 2.286 oon 0.028 0006 - 0.006 00s - 0.023 0007 - 0.00"7 oon0.011 om - 0.092 oun 0.008 UweUpper 3s 3.g4g 0149 0.149 0053 0.053 000s 0.004 oom 0.030 006s 0.068 oot 0.040 ous 0.028 Boy Perit oor 0100 Entry Period** Pascoe Yeas omy oon Baseline Years Nowe 7". Worked stun log 'natural log 2195408v 1997 *1994/95 vs 1997 O.013 0.003 0.100 0.011 0 -o2n ois - 0.212 0.186 6 Oo~o0"19 002 .76 - 0.019 0,026 : M_No24E2200 3M_MN02482200 11779999..00003388 "TTaohlbrceomI11I1lT.ls. iMMniigxxeePddoMMc(oo~dleellDCCeooteesfrffmiiciiincnaantltslF[tosftiimmTaaleeys.s,,rSStteannd"daasrCddhaBFmnr'gooer.sq (n(S5cE1l))o,,ciPPn--gVVPaalFluoOessAaanandndd99t55e%%CICononenfrfaiicddteeinnoccneewiLLtiihmmiitss `Numberof Year ofObservation of Atver Subgsoup A (1995, 19aod920070) Make Employees from Testing Polenlial Delerminanls of'l'riglyclidej Change Including PFOA and the Int~raclion wilh Number of Years of Observalioq of Anlwcrp Subgroup A (I 995, 1997 and 2000) Male Employees 95% Confidence Limits 95% Confidence Limits ad Page 39 of 63 tree Intercq)l pron PFOA YeusOmervion Years Observulion PROAx YeusOls PFOA x Yca,'s Obs AeAge a BMI Drinkadey Ddnkdday Cgmetesiny Cigareltes/day WBBaaesseellbiinneeeYYeeaoarrss Worked Coden ator 3.104 om O. 182 0167 0.167 0061 - 0.061 "0007 - 0.007 oom0.039 oom - 0.082 000s0.008 00%0.036 SBSI~. 1063I .{X)3 oust 0.051 [ 0.037 oon0.011 oon0.031 omo 0.030 00st0.051 oo2 0.012 oonO.PAI pee _p-value on .009 or~001 pr< .0001 <r < .0001 .83 x.20 ".12 =.52 ".40 lLoowweer oss0 0.880 ooo. 0.079 oo0.091 -00m - 0.084 006 - 0.069 "oom - 0.O21 "os - 0.186 oon - 0.017 | oon - 0.049 Upe Upper E5.328 02s 0.286 oan0.241 "oo - 0.039 o0s6 0.056 00 O. 100 oom 0.023 oon 0.O33 ono 0.120 nalmal lloogg _o2se2201 3M_MN02482201 11779999..00003399 "Tle 11C. Mined Mode oer Fnac, Smid ros (SE). P-Vnd i95%lConfoidensce Lit "l'ablc I I C. Mixed Madel Cocl'ficicnt I'.'stimaLes, Standard F.rro,~ (SE), P-Values and 95% Confidence Limits ro Tesin Pain Decrinas of Higheen:Chane cainPFOAand he krncion wilh I'rom Tcsling Potential D~terminanls of Tdglyeeride" Change Including PFOA and the Interaction with Noerof Yeh ofOsrvationof Aster Sgro, 159 snd2000MuleEyes Nomher o[ Years of Observ:dion of Antwerp Subgroup B 11995 and 2000) Male Employees sto nee oo Intercepl Fron PFOA [ER Year~ Observation POA Yerobs PFOA x Yeln's Obs neAge maBM ! Denke DHnk~y Cipuetcusy Cigm~ttc~d~y Bate ves Ba~li~ Years J Worked aug #natural log Gemew fficion! ams2.77.5 oon0,097 ----0.005 oun 0,0008 oars0.019 I0.~2 ome0.038 ry0.022 oom - 0.~2 spe S E osm0.523 omI).038 ,, vonI).01 ~ oun 0.009 oan0.01 I oa0.019 oso 0.050 oon0.1X)7 oo0.012 loe smCasenuetmine is lEy_alue ooo mm amo ,~ .(KX)I oo om .02 " om won .~11 oon oo .93 ator oon . I0 wPn"yn o0oo0ooomm2 oooooomnns .45 95% Confidence Limils L~wer Upper 1.720 3.830 0.019 O. 17/4 - 0.033 0.042 - 0.017 0.018 - 0.004 0.04 I 0.003 0.08 I - 0.062 O.00g 0.138 0.036 - 0.026 0.021 w_woze2202 3M_MN02482202 1177999..00004400 AComny M Compaay . Fenn Page 41 of 63 TTaabbflflieei'oom1ImIDTNTD.ue.esrMlMiiiinenixgxreePPoddfoeMlMeYnneeoatadiealrelsloDDCCfeoOoteebeflmsftieic~riicvecnJaaltnlritIEsoLmoniosftfnoiTfimTeriaAisntgtel,lswya,eecSSertrntrpaaindnseddS~aaurrbCCddghhraEaaonnnouoggprreesCIo((nS(SccEE1l)u9l),,9du7iPPang--gnVVdPPaa2FllFu0OuOe0ssAA0na)aandMnnddda99ltt55hhe%%eeEImICCnpnotolaennorfcafyiticedditeeeioonnsnncceevwiLLitliihhmititss Number of Years of Observalinn of Anlwerp Subgroup C (1997 and 2000) Male Employees 9955%% CCoonnffiiddeennccee LLiimmiittss so Ie Intercepl pron PFOA Coffeen SG Coefficient aus 0104 3.285 0.744 [= oo 0.032 O. 149 phe p-value 001.0001 5 83 loLowwesr 11.776690 0am - 0,280 Ue Upper sor 4.80 I ou 0,344 Yeus Observation Years Observation PROACYemOm PFOA x Yea~s Obs TMAge. aBMI Drinkatey Drinks/day Ciguencsiy Cigarelles/day -0072 - 0.072 000 0.020 ~ovos - o.tX~5 0057 0.057 00s - 0.025 oo0.019 oa 0.063 ost 0.05 woe o.OI 6 oo0.030 ost 0.08 I ous 0.t)08 x om ooss 26 - 0.203 0.0.58 En -o087 ois .70 - 0.087 0.128 nn oss ons 77 - 0.038 0,028 = -0008 om .08 - 0.006 O. 120 a6 0195 ous 76 O. 195 0.145 os 0002 [3 .032 0.002 0.036 WBBoaasdseeleliidnnee YYeeaarrss oom 0.010 oot0.02 I -- 5655 SE 003 - 0.034 00 0.053 Worked "nauni ~natufal lloogg _Mo24e2203 3M_MN02482203 11779999..00004411 Tle 1, Med Mod Coitns, SmsGE.P-Vd5i% Ciodsec is Table I IlL Mixed M=glel Coefficieqt F.sfimales, Standard Errors (SE), P-Values and 95% Confidence Limits Toso Pacm Doa o Ther nnd Cha e hc Fe RaO to ih front 'l'esling Potential Determinanls of "l'riglycerid~ Change Including PI~)A and the Intcraclion with of Se el ores Number of Years of Ohservation of Decatur Male Employees Fas M Company Page 42 of 63 -- J Inlercepl 2m aser oo Co{?nutefificcimefnl __ oSis ~, 2.581 0..%7 <app-vaalluee < .000 I 9955%%CCoonfindenfceLiLiimmdiittsse_n__c_e_ woower L~)wcr 1.450 sz UpUppeperr 3.712 PFPOFOAA. OAsYam Years Ohservation PFOA x Years Obs 00.005s4 ---- - 0.028 um0.~2 000.14~66. wz0.022 ous0.1~8 224 -- 000.03377 oun ans .20 - 0.071 = oot aon .85 - 0.014 o02e14s5 0.015 0.017 Ase a ours wr, om oso aon BMI Dray om am ass ass Drinks/day Pr oons I " ao aon Cigarettes/day [-- om om o aos am Entry Pe,iod** Bete ves aon ont " aon oo ed Baseline Years Worked ration #natural log eon *'!994/95 vs 1997 -00.0.0~088 0.073 - 0.038 0.~5 0.274 0.~9 Oo.Oo1n3 0.o!2 ~ 0.0~) -~. 0.~ O. 109 0.011 9.9s5 < .~1 .70 .I 6 .01 .44 -- 000.02288 0.050 - 0.235 - 0.002 0.058 -0,013 00.002266 0.096 0.1.58 0.012 0.491 0.030 scan 3M_MN02482204 11779999..00004422 PCiunasn Page 43 of 63 "l'aTfuhrlloeem112T2..esMMtiiixnneegddPMMeoonddaeell CCDooeefefffnicinineinsnl aEFn.ssatoismftaTtresisl,SyStctaaennrdddaaerr'ddECEhrxaToonrsgse((SSIEEc)).i,dPPi--nVVagalTluuOeessRaaannnddd99:5t5h%%e ICCnootnenfrfiaidcdeteinnoccneewLLiim hiists from Testing NumobfYeearrs ofObucvof Aantwierop anndDecatur Male Employes Polenlial Determinants of Tdglyceride~ Change Including TOP and the Interaction with Numl~r of Years of Ohscrvalion of Antwerp and Decatur Male Employees 95% Confidence Limits 95% Confidence Limits = Intercept Tor TOP E-- iCucflicicnl 2002 2.612 "ous 0.053 suSV ~ oa0.334 aon 0.020 pase p-value <o001 < .0001 ~AX)8 Lover Lower 1953 1.953 oo0.014 Upper Upper am 3.272 00m 0,093 YearsObservation ~00005. ons Yeur~ Obscrvalion - 0.0005 0.013 = oom [3 .97 - 0,027 0.026 TOFxYesObs -00005 0004 TOF x Years Obs - 0.0005 0.004 a -ooos 0007 .91 - 0,008 0,007 Ase 0004 aor El ~oi0 oo 0.(~H 0,007 .57 - 0.010 0.019 0 00s 0009 <.o001 oo oom 0.066 0.009 < .0001 0.049 0.084 Drinkadey oom [3 Drinks/day - 0.03 i 0.032 Er oom .34 - 0.095 0.033 Cigmetesiny wont oa 002 000s oon Cigarelles/day Locuiont oom om as om 026 ~tion* Ey cits ooms om 2 ass 02% EnlW I~riod Basel Years 0004 0007 8 0010 oom B~line Yea~ 2 Worked O.011 0.074 0.085 0.004 0.003 0.098 0.(171 0,007 .0002 .45 .23 .58 0.005 - 0A 19 - 0.055 - 0.010 0.017 0.266 0.226 0.018 ae+Ansnalttuwraaelrllpooggv,s Decale 19945 v3 1997 *Antwerp vs ~catur **1994195 vs _Mo2462205 3M_MN02482205 11779999..00004433 le 12. itd ecso soSnbBr 5, abs nd 5% Cotes iis "rahlc 12A. Mixed M(~I Coefficimll Estimates, Standard Brrom (SE), P-Values and 95% Confidence Limils on king Pac] TeChg Pea TOF ste ih fi'om 'l'csling Polcqdnl Determinants af Triglycerid~ Change Including TOP and the Interaction with nes ooo sn pe Wis Number of Yeqrs of Observation fiw Antwerp Male Employ~s [-- 95% Confidence Limils Co re Intercept rorTOF YasOvrion Years Observation TOF Yano TOF x Years Obs -Age aBMI Dinter Drinks/day Cimetsey Cigareltes/tlay Byres Entry Period** baton Baseline Years Coomcem Coefficient sus3.078 oss " 0.053 00160.016 0000 - 0.0007 oun0.009 ose0.042 om- 0.032 oars0.018 ats - 0.045 on0.007 SB~;1~. as0.395 aon0.028 an0.017 aos0.0[~6 ao0.009 aoO.014 oon0.034 ones0.{X)5 on0.101 oon0.011 puke pvalu om< .00O I -.0~ xs.35 .90 =.32 oom0.004 .34 as.0005 .66 Ls.56 low Lower 202.294 oz - 0.002 oars- 0.018 oz - 0.012 own - 0.009 anne0.014 wom- 0.099 I0.008 ois- 0.245 ome - 0.016 UpUpeperr 21623,862 -0.107 oo0.049 oom0.010 -0.028 om0.071 oiss0.~35 ao0.029 oss0.155 oom0.029 EWH oAedeeersnereesemmeser :m eataersmme mmniS reriiiPA n emperet mere for #*nnaattumc'ialllologg. ' **1994P-~5 vs 1997 cain 3M_MN02482206 11779999..00004444 "Tl'aabbllreo11m22B.Te. sMMtiiinnxgeePddoMMonodtdesell CCDooeeeffficfkicincul iEseotinfmTtarsteg,sh,cSSettaannndddeaa"rrddChEEearrrnoogrress ((cSSEE)),,lPP--VVaaaTlluuOeeFssdyande9955%% ICConnocfnaifcidideoennnccweeiLLihimmititss from Testing NuYmeasbof Otecrvarton or Desatar MaleEmployees Potential Determinants of Triglyceridee Change Including TOP and Number of Years, of Ohservation fi~r Decalur Male Employees the Interaction with HY Company I'agc 45 0f63 omcodecclmis 95% Confidence Limits ners Inlercepl Tor TOF Coen Coefficient 200 2.644 oa0.031 s0SE ser 0.563 [ 0.030 pe p-value <oo0n < .0001 .29 leer Lower on1.521 os - 0.028 per Up.per ans 3.766 oom 0.090 Year Otvervation 0435 om ow om own Years Observation TORxYamon 0u04 00s s oom oois TOF x Years Obs Ase 0002 oo om ons Age Ba ou oz <tr 0050 0010 BM! Drinslday 0000 0099 7% oz 0166 Drinks~day r-- 000s oon 0003 oon CigarItem/day - 0.035 0.004 - 0.002 0.073 - 0.030 0.005 (I.022 0.005 : 0.014 0.012 0.099 0.004 . ! 2~ .45 .90 < .0001 .76 .20 - 0.079 - 0.007 - 0.029 0.050 - 0.227 - 0.003 0.009 0.015 0.025 0.010 0. ! 66 0.019_ Ear Periods oars om Entry Period** Basco Yeux am aon Ba~:liae Ycah~. Woke Worked "anus og enatural log "15a 1997 **1994195 vs 1997 0.275 (I.O~F~) O. I 11 0.01 I on ooss oa .01 0.055 0.494 " --- 03 oso .44 - 0.013 0.030 aM No24E2207 3M_MN02482207 11779999..00004455 "Tl 13. MixedModel Coffin mats, Sandu iors(SE).P-Vlues nd 95% Confidence Limits Table 13. Mixed Model Cocfficien! Estimales, Standard Errors (SE], P-Values and 95% Confidence Limits from Tesing Peis Decinoaf ArlkatlisnePhosphate! Che lingPROS nd he nation wih from Testing Polential Determinants of Alkaline Phosphatase~ Change Including PFOS and the Interaction with Numberof YeasofObcrvation ofAntwerpsnd DecMaaeEimpluoyres Numl~r of Years of Observation of Antwerp and Decatur Male Employees ard 1 Company ~ge 46 of 63 95%Confidence Limits 95% Confidence Limits sneer rs ]nlerccpl pros PFOS Yeas Observation Years Observation fee Coefficient am3.789 om 0.002 -0051 - 11.051 SESE aim 0.176 oun O.(R~) ouO.(RJ6 phe p-value <tr < .0001 n.87 <0 < .O00l lows Lower saz 3.442 oon- 0.017 0002 - 0.062 Ue Upper wa4.137 ono 0.020 000 - 0.(140 PROS YearsOt PFOS x Years Obs areAg aBMI Driokttey Drinks/day ra Cigarelles/day Locaiont Location* Baty Periods Entry Period** Basco Yeas Baseline Ycnrs Worked Worked igyeerides" Triglyeerides~ oo 0.002 ous0.005 ~0007 - 0.0007 -o00 - 0.001 oo0.003 -020 - 0.242 oom0.098 0006 - 0,006 oi 0.113 oon 0.002 ows0.004 oa0.004 oo0.014 oan0.O01 ao0,049 om0.037 oan0.004 om 0.024 :, a.47 x.20 -.88 ".94 on.03 <0 < .0001 Ir.008 0. I0 <0 < .0001 0003 - 0.003 0003 - 0.003 -000 - 0.009 00% - 0.030 [ 0.0004 0x8 - 0.338 ons 0.025 oon- 0.013 00670.067 0006 0.006 oon 0.012 oom O.OOg ou 0.02g 0006 0:006 01s - O. 145 om0.171 Ir 0.001 06 0.160 'a*nAaotuttrvaelrlopoggve Decatur "IOS vs 1991 *Antwerp vs Decatur **!994195 ~s 1997 aM No24E2208 3M_MN02482208 11779999..00004466 Ia -, mpnny Frais P,,gu ~,7 of 63 froT"mTaaTbleleest11i44n..g MMPiioxxeenddtMMao(DdKeeleltlCeCoroemfil'nificeciseennotf IB~AtslkliiamslaietnesesP,,hSSotstaapnnhddasatrradds,erE'rCorohsrasn((SgSEIe~).,),nPPc--VdVaialnlutgmessaPanRnOdd9A95a5%%ndCCtohoennIfifdnteirnadcceeLtLinoiimnciwtesisth f,'om Testing "NumberofYeasofOsrvation of Awe ndDecatur Mal Employees. Potential Determinants of Alkaline Phosphatase~ Change Including PFOA and the Number of Years of Ohservalion of Antwerp and Decatur Male Bmployees Interaction with 95%ConfidenceLimits 95% Confidence Limits si oe Cole Sp ewe e UUppeperr Lower Inercep Intercept EN PFOA YearsObcrvsion Yea,~ Obserwlion POA Yeas Obs PFOA x Years Obs Ase Age BMBMI Drinkakiy Drinks/day r------ (2igarelles/day 25 3.785 000s 0.005 0.47 - 0.(H7 0001 - 0.001 000s 0.005 -00009 - 0.0009 0002 - 0.002 oon 0.003 01m O. 176 oo(I,(} 12 ool0.006 oo0.002 oo0.0114 0004 0.004 ons 0,015 ooo0.001 <oo01 < .0001 ".69 <o001 < .0001 @.62 w.19 a.85 .89 o.03 2431 3.437 en - 0.019 -ooss - 0.058 -o00s - 0.005 0002 - 0.002 -0010 - 0.010 "00st - 0.031 00004 0.0004 am 4.133 oom 0.028 ose - 0.036 oo 0.003 oon 0.013 ooo 0.008 oom 0.027 0006 0.006 Locaiont Location* BaErntyryPPeerriioodd*s* BBaWsoacsrlekileinndee YeuYears Worked 020 - 0.243 0100 0. 100 00s - 0.006 oon, 0.049 : ose 0.036 oot 0.004 <o001 < .0001 on.007 3.09 "om - 0.340 oo0.028 -ooue - 0.014 "- 0o.1r4e7 om 0.172 0001 0.001 Tigeeided ona oo <oon1 oss oi Triglyce,'ides# 0. I ! 4 0.024 < .0001 0.066 0.161 ~"nnaaAttaunrnatl ltlooggaw. Deecrsipr 4*A1ntw9er9p vv4ssD919e9c57atur **1994D5 vs 1997 aM_No24E2208 3M_MN02482209 11779999..00004477 iss "Table 15. Mixed oseCost stoic,Standan)Eres (5).-Valossnd 5%Confidence Limits Tahlc 15. Mixed Mod~l Coeffi,'icnl I.~:~lil)lalcs, Sl~,ndard Errors (SE), P-Vp,tues and 95% Confidence IJmits om Testing Ronit Deer ofAlkaliPhosphCtosane InclocingTOP ad he Iscron ith from "l'~sling Potential Determinants of Alkaline Phosphutas~I Ch:mge Including TOV and the Inler~tion with NabofeYearrsofOecrvofiAwoen snd DecMalaeEtmpluoyres Number 0f Years nr Oh.~rvalion of Antwerp and Decatur Male }]mpIo~ees _ Co trent ]nlcrccpl TorTOF Yon Oberon Years Observation TOFx Yaron TOF x Yca~ Obs ae Age wi Drikoay D~nkdday Coote amy 3.78') "oom - t).(~ 0049 - 0.~9 -000006 - 0.~6 ous 0.~5 oon oo - 0.~2 SL omO. 177 oun O.(~F) owe O.(~ [ 0.~ 17 oonm0y4 0.(~ ons 0.015 pe <oo0 < .0001 .~) <0 < .~ I Ea.97 =.19 ".9 i LoLSCodmelinis 95% (2onfidenc~ Limits over Upper Lower Upl~.r a wm 3.441 4.138 -oom ours - 0.019 0.018 0000 007 - 0.0~0 - 0.037 0003 0003 - 0.003 0003 oor - 0.003 0.003 0.012 00 ons - 0.0lO 0008 oon ous - 0.031 0.028 Ciguetediay 0003 Cigare~ledday 0.(~3 Locaions ozs Bay Pees 0100 ~try Period** ().1~ 001 0.(~ I ons ao0.036 .03 <o001 oon .~7 os 0.0004 "03- 0.342 ous 0.028 oo 0.00~ ues - 0.148 om 0.172 BWaosrekliende Yeas 0006 ou WoAcd a0 oon - 0.013 0o00! Tigers" ons om <a ous we T~glycerides= 0.1 ! 5 0.024 < .~ I 0.068 0.1152 nS"anAatlnaunreatrl plloovggsDecsor "E100 ve 1997 *Antwerp vs Decatur **10A/95 vs 1997 w_o24Ez210 3M_MN02482210 11779999..00004488 uy "Tale 16. Mined Model CaelTiin Fstimais Standard ror SE), P-Valucssnd 95% Confidence Limits "l'ahle 16. Mixed Model Coel'ficie.~t I~tim,',es, Standard Errors (SE), P-Values and 95% Confidence Limits fio Testing Poesia Deterninais of GGT hang IncludingPROSand he erin with from Testing Potential Determinunts ofGGT~ Change Including PFO$ and the Interaction with Nunberof Yeas of Oervaon of Anwenrd DeMcleaEmpuloyres Number of Years of Observation of Antwerp and Decatur Male Employees trp Inlcrcept rosPFOS YousOtvervion Years Observation PROSxYemOb PFOS x Yea~ Obs IAgc aBMI Driokiay DHnkgday Clguretesiay Ciga~lle~day Coffe C~mfficienl Ls1.883 oo - (}.004 0475 - 0.075 0004 0.~ oom - 0.~13 000s 0.~5 oon 0.~2 00009 - 0.~9 suSE am 0.3"/3 oom0.020 oo0.012 oom0,~ woos 0.(~)8 0 O.(~J oo0.03 I ous0,~3 pose p-value "oon < .0001 ",84 <a< .0001 2.42 74 .59 ".18 mn.77 OS ConfienceLimits 95% Confidence Limits Lover pe Lower Uplx~r Lu 260 1.146 2.620 03 00s - 0.043 0,035 oom oust - 0.098 - 0.05 i -o00s oon - 0.005 0.012 0019 oon - 0.019 0.013 03 oo - 0.013 0.024 00 oi - 0.020 0.104 0007 dons - 0.007 Locaion 00% oi % 00% ono ~alion* Eny Pairs ass om <0 om osi2 ~nlry Period** Dascine Yeas os oo -0007 os Ba~linc Y~m~ Weed Work~ Tapeeroe" ozs) [a <0 ois2 03% T6glyce6des~ - 0.096 0.358 0.~8 0.251 0~1 04 (},078 0.~7 0.050 .36 < .000 ! .30 < .0001 - 0.030 0.204 - 0.007 0.152 O. I I0 0.5 ! 2 0.024 0.350 't"nAautnui,n~vleolovgga Decatur *"AHin0twRAerRpSvvsaD1e9c9a7tur **1r~4195 vs 199"/ aw_o2eez211 3M_MN02482211 11779999..00004499 able 17. Mined ModelCocfficica imtcs, apd rors SE, P-Valucs nd 95% ConfidenceLimits l'ahle 17. Mixed Mt~ll Coefficient I:.stimales, Sland-rd Errors (SE), ['-Values and 95% Confidence Limits fonTsing Poenial DeterofmGGiT*nCheansge Iclding PFOA adhe nection wth from Testing Potential Determinants of GGT~ Change Including PFOA and the Interaction with Nomerof Years ofOscrvoafAinwoernp snd esMlseEmoployrees Number of Years of Ohscrvalion of Anlwcrp and Dccatur Male Employees 958Conune Limits 95% Confid,~nce Limits aeons Page 50 of 63 ............ me ern Intercept Pron PFOA Yea Oberon Years Observalion PROAxYeunObs PFOA x Years Ohs AwAge aBMI Collen Coefficient 176I .a76 "own - 0.0(F,t 00m - 0.077 0005 0.005 0002 - 0.002 oo 0.fl04 S0 SI~. om 0.374 ous 0.025 nz 0.1112 ous 0.005 ous 0,008 oun 0.009 pee p-value Zon < .(K)O 1 no.72 <0 < .0001 .29 a6.76 -.64 ewer Lower LsI. 138 ooss - 0.058 0100 - 0.100 oom - 0.004 -oos - 0.018 -oou - 0.014 Upa Upper 260 2.613 000 0.040 00s - 0.054 oo 0.014 oo 0.013 oon 0.023 Drinking oon ou a -o0i9 0105 Etrink~Jday Cipuretesny ~00007 000 = aon oos Cigarctte,~day Lociont 009 0108 EY 031 ous Location* En perodss 038s om <o001 ozs oso Entry ['eri~l** Busine Yeu ao 00s 0 0007 oo Baseline Yeut~ Worked Worked 0.043 - 0.0007 - 0.097 0.355 0.008 0.031 0.003 0.104 0.077 (}.008 .17 .82 .35 < .0001 .30 - 0.019 - 0.007 - 0.301 0.203 - 0.007 0.105 0.005 0.108 0.507 0.024 Theater! 026 ost <0 ois 0356 Triglycerides~ 0.256 0.05 ! < .0O01 0.156 0.356 nul og #natural log "AlvesDeca *Antwerp vs D~catur "Hio5uns va 1997 **1994P)5 vs 1997 aw mozeez212 3M_MN02482212 11779999..00005500 AciSgs M C'amp~ny Page 51 of 63 'l'ahle Ig. Mixed Model Coefficient I,'-stimatcs, Standard Errors (SI~.), P-Values and 95% Confidence Limits om Tsing ei Deans GTCoane oo TO se rion fi'am Testing Potential Determinanls of GGT~ Change Including TOF and the Interaction with Narheof YoofOruvaison of Awe sod DoMilcEmpluoyes Number of Years of Ob.~ervalian of Anlwerp and Decatur Male Employees 958 Cones Limits 95% Confidence Limits c [-- om um moaonw pCuokem LoLvi er 2U0p08p lnlercep! or own TM " om oon TOF Coefficient 1.870 0.002 SE 0.374 0.020 p-value < .0O01 .93 Lower I. 132 - 0.037 Upper 2.608 0.04 ! Yess Obervion ~~ -00m oun <omn ion ~oos4 Years Observation ToPvanOn ont ow x os oon TOF x Years O|xs - (i.079 0.004 0.013 0.003 < .0001 .25 - 0.104 - 0.003 - 0.054 0.011 ne om TM as oon oon Age - 0.003 1).008 .75 - 0.018 0.013 a ows own = oon oa BMI 0.005 0.009 .57 - 0.013 0.024 Drnktny 000 om n oon oor Drinks/day 0.043 0.031 .17 - 0.019 0.104 Cpe ose oon n our ous Cigarette,/day - 0.0009 0.003 .77 - 0.007 0.005 Lacan ous ator oa on Location* - 0.088 0.104 .40 - 0.294 0.117 By oes os wm <om oa os Enh'y Period** 0.352 t}.078 < .0001 0.200 0.505 Bacto vous ous aces at our oa Baseline Years Voted Worked 0.008 0.008 .31 - 0.007 0.024 Tighe! wan aso <a wo I Tdglyccrid~s~ 0.249 0.050 < .0001 0.149 0:348 troy ~natural lag "Haver Dec *Antwerp vs Decatur is **1994/95 vs 1997 awmozsszzns 3M_MN02482213 7197999..00005511 sl 1. MedMod Coun tines, Sard irs(55. Vil95% Cuties : Lins Table 19. Mixed M~el Coefficicn! Eslimates, ~t.',ndard Errors (SE), P-Values and 95% Confidence Limits Ting Po Ds ofAST Chg le PRO a co i from Tesling Potential Delerminanls of AS'I~ Change Including PFOS and the Interaction with Nantes Yous of rerio oer Des MlEpos Number of Years of Ohservalion of Antwerp and Decatur Male Employees 95% CondLeivis 95% Confidence Limits PR Company Pag~ 52 of 63, --_-- oo ecem ...................t_:_oel'ficienl rt 10m lntercepl 3.080 ros aoe PFOS 0.010 VernObrien 0009 Years Observation - 0.009 Pros veusons 1007 PFOS x Years Ohs 0.(~07 re os Age - 0,008 wa aon BMI 0.004 Orta amo Drinks/day 0.030 Cptesisy om Cigarcllcdd~y - 0.003 Lain on Lncatimt* O. 102 ny es oom Entry Period** 0.039 Bute Yen aes Baseline Years Ve Worked 0,005 erst TM Triglycerides~ 0.063 SS EE oonO, 198 oonO.t) l I aor0.007 os0.003 on0.004 oms0.005 aoe0.018 oz0.0{)2 ass0,053 oon0.039 aon0,004 I0.029 pe p-value com <~ .0001 ,39 w.19 .79 os.05 a.47 u. I I @.07 -.06 .32 2.22 .03 lLoowweerr 2a2.689 oon- 0.013 "oo- 0.024 aos - 0.005 oot- 0.016 "oan - 0.007 "oom- 0.007 ome - 0.006 oe - 0.206 ous- 0.038 ous - 0.003 os0.005 UUppppeerr san3.47 I oon0.032 ous0.005 ax0.006 "oow0s - 0.00005 ao0.014 one0.066 oom 0.0002 sors0.003 ae0.116 oo0.012 amO. 121 rant Inalural log Cheaecm ~'Antwerp vs Decatur sw **19~4/95 vs 1997 swmczizzis 3M_MN02482214 11779999..00005522 "TTaobbleefr2200o..mMMTiienxeeiddnMMoPedelenl CCioDsefcfDfiticctiieeennttrE[":mistniime~uo,slfcn,sA,StS$T1tsapnddCaahrraddnigEeorrroIrnsscl((SScEEi)n),,gPVP-FVaOalAulaenswudandtdee9955sI%%teCCscootnifniodnetnwcidtehLLiimnitss from NanherofYea af Otcrvof Aantwierop and DecMalaeEtmpluoyeres Testing Poteatial Detemfina.t~ ofA~ Chm~ h)cluding P~O~ ~nd th~ lntcJ'~ction wilh Numl~r of Y~a~ of Ob~crvalion of Anlw~ and D~a~ur Male ~ploye~s aeM Cunan 958% Confidence Limit 95% Confidence Limits JE Inereps Intercept proPFOA YYeeaa~r;s~ Orton Obscrvalio. PROAXYemOb P~A x Yeat~ Obs I Age MiBMI Drinkadey Dfink~day Cigmtestiny Ciga,~tlcgday Locaiont ~alion* Ey Protos Enl,T Pcrital** BBWaoasr~eklliienndee Years Years Work~ ( ],~i'ficicnl 0s3.053 om 0,027 - 0O0.(g0)88 0002 - 0.~2 "oom - ().~)7 0004 0.(~ os0.030 0003 - 0.~3 0097 - 0.097 oon 0.04,1 00040.~ SES I '.' 019 (I. 109 ois0.015 o0.o1~r7 0003 0.[~3 0004 0.(~ 000s 0.~5 oo0.018 oo0.1~}2 os 0.053 ono 0.039 oo0.~ pale p-value <0 < .O(R) I .06 x.28 a.41 0.08 .39 0.10 o.07 o.07 2.26 z.27 Lower Lower 2662.661 "00m - 0.002 oon - O.O22 0008 - 0.008 -oms - 0.015 Es - 0.006 006 - 0.006 -0006 - 0.006 0201 - 0.201 oon - 0.032 -0003 o 0.003 UUmpl~rer aus 3.445 0056 0.056 00.000066 00.000033 oon 0.0008 oots 0.015 oss 0.066 00002 0.0002 00s 0.008 ono 0.120 oon 0.012 Tigres" oust Tfiglyceridcs' 0.054 oo0.030 o -0004 on .07 - 0.004 0.113 "~"nAnanaltuawranelrllpooggvs Decatur 419945 ve 1997 *Antwerp vs I)calur **199419.5 vs 1997 _ozsez215 3M_MN02482215 11779999..00005533 le 21.nMeiniednModP el Cot c seS tsASSTi nCher.si 5T- OF 5 dh orCcointienc ii Table 21. Mixed Model Coefficient I:.stimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determimmts of AS'I~ Change Including TOF and the Interaction with NNuumlmmroboffYYeeeararrss ooff OObhsseerrvvaattiinonnooff AAnnttwweerrpp aunndd D DeceaturcMMaalale9EEt mmplpuoloyyereeess Con 9955f %% Coi nfidd enceLe Liimmitin tss ce --i meen Intercept TorTOF [I Years Observalion ToFxvamon TOF x Y~,~ Obs aAge aBMI Dray Drinks/day psy Cigarette 'dday Losin Location* ry ers Entry Period** foBaseline Yeats es Worked CoCoceffficieint clens S,',;$E sas wo, 3.058 O. 198 : oor oTMm - 0.0(19 ows om - 0.006 Cams om - 0.008 oom ours 0.004 oom oars 0.029 03 Pr - 0.003 os ass - 0.095 aon am 0.039" aoos ao 0.005 0.1108 0.002 0.004 0.005 0.018 0.002 0.053 0.039 0.004 TrTirgilgylyccecrriiddeess't 000.50588 000.02299 pr tnatural log "hs bc *Antwerp vs Decatur Aston *'1994/95 vs 1997 pwp-vealeue com < .l~O I -a.24 .79 .06 ".40 " 12 ".07 =.08 .31 x.24 0.055 lLoowweerr 2066 2.666 aos - 0.005 EE- 0.024 ams - 0.005 ome - 0.016 ams - 0.006 oun - 0.007 os - 0.006 "oi- 0.199 amr - 0.037 "aos - 0.003 0.00.000000033 UpUpppeerr 2a3.449 oot0.04 aos0.006 oom0.004 aos 0.0002 oors0.015 ooss0.065 oom 0.0002 ao0.010 ans0.115 aor:0.012 o0.l11e6 sumczizzie 3M_MN02482216 11779999..00005544 Tale "l'ablc 22r22.o.MmMiTxiexseteiddngMMoP(soue.llelelnCCooeelfDificceiietnnte! HErsmlshineanotfea,sAn, LSStatTasnnddCaahrrddanFEeroroIJs.n'scl((cSSiEEn))g,, PPP--RVVaOalSlouaeesnss.dannhdde9955I%%nCaCocnotfniifodidneenwncceiesLiLmimitisls from Numerof Yearsof Ghcrvainof Testing Potenlial Delerminanls of AL'I'~ Aniwerpsnd Decatur MeleEmployes Change Including PffO$ and the lnlcraction with Nmnber of Yea~s of Observation of Antwerp and Decatur Male ~nployees 95%ContgenceLimi 95% Confidence Limits J _ Comew Si puke .........................!~ ~.~!'fi__c_J~LLl............ .'51.~........ .~ Inerep 2501 om <o001 Intercept 2.501 0.273 p-w,luc .~ .0001 Lower Lower 15611.961 Upter Upper ou 3.041 pros + ono 006 st 0021 oon PFOS " 0.010 O.O 16 .54 - 0.021 0.041 YeanObservation 0095 oot Yems Observalion - t}.t}95 0.010 OSs YemObs 00000 004 PFOS x Years Ohs - 0.00003 11.004 ne 00000 00s Age 0.0009 11.006 <a "ous < .000 I -000s .99 - 0.008 5 -oon2 - 0.012 ons - 0.075 os 000 0.010 a 000 oo w 000 os BMI 0.010 0.007 .17 - 0.004 0.024 Dinky Drinks/day 002 - 0.012 ous 0.025 0062 oo .63 - 0.062 0.038 Ciguetesiny -0008 [= Cigarelleshlay - 0.008 0.002 on -o0iz .130 I -0.012 -0003 - 0.003 Locuions 008 on L~alioll* - 0.088 0.073 .23 03 - 0.233 00.005566 Bay Peas om = <o00t 022 ous Entry Pcniod** Base Years oon 00s - ooo oo Baseline Years Worked Worked 0.329 O.001 0.054 (I.005 < .000I .84 0.222 - 0.010 0.436 0.012 Tigris" 0159 ooi0 Triglycerid~s~ 0.159 0.1140 conn 09 os .0001 0.079 0.238 phd A#*anaaAturnal otlovggvsDeecray "109vs419S97 *Antwerp vs Decatur ** 1994195 vs 1997 aw mozeez21 3M_MN02482217 11779999..00005555 Pcs i'ag~ 56 of 63 "Tole{r223o3.. TMMeiisxstecidnMMgPo,~tdlecelCCoocffDfficeiicenn!r~Essmtlilii~nl:sn|oelcfsnsA,,tLSSttsTaapnddCaahrraddrrEgoerrroI~s(n(SScEE,),lPPP--uVVFaaOdllAuoeaissnnnadnhddge9955e%%CaCotnofniifinddeennwcciteehLLiinmiti[ss fron~ amber ofYears ofObservationof l'cslinB Polcnliul Dclcrminanls of AL.T= Number of Years of Ob~crv.'=tion of Aiwerp andDecaturMaleEmployes ChunBc lncludinB P~'OA and the lnterac|ion ^mweq~ and Decatur Male Employees wi~h oskC9o5%nCfonifideencre cLimeitls imis --nee [ntercepl pron PFOA o Coffeen Sh ................( h~cl'ficicm __ 2a am 2.4?9 SI~. 0.272 ams ama 0.015 O.020 phe p-value <o001 < .0001 a".46 lew~wcr 1901.942 ~oos - 0.025 Umer Upper an 3.016 as Yeas Oration -0.107 uo <ao0r pr 0081 Years Observation - 0.107 0.(110 < .~1 - 0.126 - 0.087 PROACYeisOb 0005 oon P~A x Yea~ Obs (1.~15 0.(~ ree ~00001 os Age - (l.l~l -0003 ons .19 - 0.003 0.013 5 -onut oon -0.01 l 0.011 oa oon a Drinkadey 000m os D~nk~duy - 0.(~) 0.025 5 om 02s - 0.003 0.025 -ooss 000 .72 - 0.058 0.040 CiCgiagratreelsletgidaayy -- 00.0(~071 02 0.(~)2 0 002 oom .~I - 0.012 - 0.003 Location "00m om ~ation* - 0.079 0.072 om 064 .28 - 0.222 O.Od4 ry Piss om 53 co ons [= ~nt=y Pcri=al** Base Years 000s 000s "000 oon B~eline Years Worked Worked 0.330 0.~ 0.053 0.~5 . < .~I .89 0.225 - 0.010 0.434 0.0| I Tigers" ost ont Tdglycerides~ 0.151 0.~ I 000s oon om .~3 0.071 0.231 Ansar log, #nalural log "Aatvervps Decatur *Antwerp vs l)catur 19945 ve 1997 ** 1994/95 vs 1997 _ozsez218 3M_MN02482218 11779999..00005566 ad "ible Table 22f44.o. m MMTieinxueeiddngMMoodPdeaellcCCiaoseffffDicieitiecnnmt iFsn.saitinmmsatosefs,ASSLtaaTngdaCarhrdiCEninrs'oorescS(lSFuE)i),n,PgPT--VVOaalFluuaeesnsdnanhdde99I55%%nCsCotnofnoifniddeetnncchee Limits Limils from NoYee ar ofr Oservf aion of Testing Potential Delerminants of ALT~ Number of Years of Ohservati(m of Anwerp Change Antwerp 3x) DecMilaeEmtpluoyeres Including TOF and the lnleraction and D~atur Male Employees with 958Contgnce Limits 95% Confidence Limits e[=e Coof2i47e6n lnlercepl or 0am TOF YearsOtseraion 0.102 Years Olmervalion TORK Years oo TOF x Years Ohs ne ~oo00s Age 0 oon BMI Deikatey 003 Drinks/day Cipuetesiny 00s Cigarettes/day Locaions oom Location* Ey Periods os Entry Period** Basco Yeas ooms Baseline Years Worked Worked -- ous Triglycerides~ Ctx:fficie.I 2.476 0.020 - 0.102 0.002 - 0.(1005 O.O 11 - 0.013 - 0.008 - 0.073 0.325 0.0008 O. 148 Si SI'.' : om0.273 ons; 0.016 : vont0.01 I oom0.003 000O.(X~6 oom0.007 oms 0.025 oon 0.0O2 oor0.073 o0s3 {}.0.53 os 0.005 00.00400 pe p-value Soo < .(~JOl a.2 I <a< .0OOl 0.50 @.03 a 1 I @.62 oon.oo I 2.32 <0 < .0001 ".88 00s.0003 Lover 19%1,936 -oon -0.011 om -0.123 0008 -0.004 oon-0.01 i 000 - 0.003 -0062 - 0.062 ~oon - 0.012 oan - 0.217 om0.220 pr- 0.010 009 0.069 Upper Upl~r . 201s 3.015 00st0.051 oom - 0.082 000s 0.008 oo 0.010 os 0.026 oom 0.037 om - 0.{)03 oon 0.072 on 0.430 oono,011 ozs 0.228 "asta og ~natu~al log "AntvwsDeecratpur *Antwerp vs Decatur "Emns vs 1997 *'!994/95 vs 1997 aM mozeez210 3M_MN02482219 11779999..00005577 Table 25. Mined Model Celio LiSnandicsors S,E, P-Vlues nd 9%Confidence Limits lkble 25. Mixed Model Coefficicnl I?.slimates, Slandard Erro,'~ (SP.), P-Values and 95% Confidence Limits frTsing Penis DermofaTotn ibn ChangeIningPROSand he Iersction wih from Testing Polentia112~terminams of Total Bilirubin~ Change Including PriOR and the Interaction with NumobfYeearsofObcrofvAwaertpanid Deocatnur Male Employes Number of Years of Observation of Anlwerp and Decatur Male Bmployees 95%Confidence Limi 95% Confidence Limits rn eros YenOvervion PROS x YeusObs a I Diinkalday Cparecstny Locaion EvyPeres BWaosrckiendeYeas Ctame Coefficient aos - 0.018 0433 0.033 0002 - 0.002 oon0.011 000 - 0.003 one 0.016 - 000.00088 os 0.315 "oi oon - (1.002 sSeE om oo0.014 on 0.(~119 ou0.004 ons 0.(~5 oun 0.007 ome 0.024 . oo0.002 0os6I).064 oms 0.005 : pnee p-value 2 .22 wos ".94 .02 o.67 0.50 <om < .0001 <a< .0001 ".(~4 ler Lower osm -0.811 006 - 0.046 ous0.0148 0007 - 0.007 oon0.001 -o016 - 0.016 000 - 0.030 oon - 0.012 0o6i 0.189 oon-0.01! upe Upper oi 0.142 oon0.011 ous 0.052 000 0.007 oo 0.020 on 0.010 one:0.062 0004 - 0.004 out0.44 l om - 0.022 our 0.007 Tighoerides" oom ou - 0.088 0.037 0161 oats .02 -0.161 - 0.015 otal log anatural log "Ane va Desaar *Antwerp vs Decatur SAS va 1997 **1994195 vs 1997 M_No24E2220 3M_MN02482220 11779999..00005588 Company Farr Page 59 of 63 "ibolmeT26e.MinidPoMoodDe eCoterfimciieomfnTntoes, Standard Coors (SE, -Vaocs wd95% Confidence iis "l'abl 26. Mixed Model Coefficient F~timates, Standard En-ors (SE), P-Values and 95% Confidence Limits t rb Chang niin PPO sndih Ison wih from 'r.~ting Potenlial Determinants of Total Bilirubin# Change including PFOA and Ihc Interaction with Numberof Yea ofOsrvaion of Amwer sndDecor Mile Bplcyecs Number of Years of Observation of Antwerp and Decatur Male PmpIoyecs 95%Consens Limits 95% Confidence Limits _nee J ois ovman pune Loomver oUpipeer Intercept Pron oan oor 1 oo oon PFOA ............. Coefficilll -0.315 - 0.030 Yon Obsrvion 0428 oom oot oo Years Obscrvalion 0.028 POAXYomOM 0005 oo " oo oon PFOA x Yem~ Obs 0.005 Sit 0.242 0.019 0.009 0.004 _p-valve .19 .16 .003 .18 Low~l- O.'793 0.001 - 0,002 Upr~r o.1d2 o.0~7 0.046 0.013 AAsgee maBM1 Drinking Drinks/day Cipreetiny Cigmetl "s/day Locaion Location* Bot Pies Entry Pc,'iod** [re Baseline Years Vokes Worked genie Triglycerides~ a010 0.010 00m - 0.003 oon0.014 oom- 0.008 oan0.318 ouone -0.124 oo- 0.082 os 0.005 :: oom0.007 om0.023 om0.002 I0.064 oot0.(H6 oms0.005 oun0.037 .o04 at.61 55.55 <aont.0001 . <aont.0001 on.007 a.'71 .O3 00007 0.0007 -0016 - 0.016 oom- 0.032 oor- 0.013 ss0.193 oats-0.215 ~o0u- 0.011 "oss -0.156 000 0.020 aon0.010 oo 0.060 00m - 0.004 oss 0.444 oom - 0.034 oom0.007 oo "oat log #natural log "Aner vi ecsar *Anlwerp vs Decatur io5ims a 197 **1994195 vs 1997 aM ezeezz21 3M_MN02482221 11779999..00005599 , Compaay bTlree2T7.sMinigPdoMoedle DCeocsriasnoafeTto,e StandardFos (5), Valu sd 95%Cofdece Lit fran] "i'ahle 2'7. Mixed Model Cocfficicm ILstimat,~, Standard Errors (SE), P-Value~ and 95% Confidence Limits Bibi Crargs ching TOFand he Incrscion wih froan Tesling P(aenlial ]:leterminm}ts uJ" Total Bilirubin~ Change Including TOF and the Interaction wilh "Numberof Year of Onc of Aner snd Decor Mile poy Number of Yea~ of Oh~rwdion of Antwerp and Decatur Male Employees 95% Conitene Limi 95% Confidence Limits cme wm pose Lover topes ................... Coefficient ere oe ne "ome oie Inte~cpl - 0.31 g ,~1,~ 0.242 p-~alue :. 19 Lower - 0.796 Upper 0.160 Tor +000 oon " 000 oom TOP " ~ 0.02(} 0.014 .16 - 0.~9 Yon Oberon 0429 woo os oom oot Y~ OI)s~rvalion 0.029 0.010 .(~)5 0.~9 0.~9 TORxYemon 0m oom 2 ous oo TOF x Years Obs 0.~3 0.~3 .3~ - 0.~3 0.~ Dnoreitnks oooomn oooummns 5a oo~ooo0rtn6 ooonamen D~nk~day Cipmctcslny om on <aont oor oom ~igarcttc~day Locaiant oie oot pr om oan ~ation~ BeaytriYeeass owomm ooomts "" o~ooamn0 oooomm B~linc Ycm~ Vokes Worked Tigre Er oan " "ose oon T~glyccridcs~ 0.016 - 0.(H)8 0,316 - 0.~2 - 0.085 0.023 0.(~2 0.(~ 0.(~5 0.037 < .~ I < .~ I .68 ,02 - 0,012 0.190 - 0.011 - 0.15g - 0.~ 0.442 0.~7 - 0.012 "naan log )natural log "AnvveDeecar *Antweq~ vs Decatur "isis a 991 **1994195 vs 1997 aMnezeezzz2 3M_MN02482222 7197999..00006600 re "Table28. Mined Model Coffin: stmt, Sandu iors(SE, P-Valus nd35%Confidence Limits Table 28. Mixed Model Coefficient Estimates, Standard E=TOrS (SE), P-Values and 95% Confidence Limits fomTeunPte Detrminouof Direct Bilin' Chang IncluingPROS nd he nracton with from Testing Potential Delerminanls of Direct Bilirubine Change Including PFOS and the Interaction with Number Years ofOtsvatin of Aver sd Deca ii Employes Nnmber of Years of Observation of Antwerp and D~catur Male Employees osmCodmcotimis 95% Confidence Limits [-- Co1%en2S0E 0 lntercepl ros "oon oon PFO~ YeasObservation -097 oom Years Obscl'ValJell PneOieSxYersO 0ro0u0yr6 oo00oo0ns PFOS x Yea~ Obs Coefficient - I.'156 - 0.013 - 0.097 -o.oo6 0.007 - 0.003 SE 0.204 0.013 0,009 o.,~ 0.004 0.006 Drikuisy Ddnkgday -- Cigaretlegday Locaions ~ation* Baty Perot ~try BWBouarssekcleiindee Yeus Worked ooO.O l B ~ooms - 0.0005 ous 0.076 09 0.353 ~o0n - 0,001 oom0.020 oe 0.002 : oon 0.053 ous 0.038 : ous 0.004 pee p-value oo < .0001 .29 <0 < .0001 a.is .06 st.58 .37 .79 as,15 <or . < .0001 n.74 ewer Lower 210 - 2.160 00m - 0.039 116 - O. 116 001 - 0.014 ous - 0.00O3 -oais - 0.015 om - 0.022 000s - 0.004 00s - 0.028 om0.277 00- 0.009 Ue Upper ass - 1.355 oor 0.012 oom - 0.079 oon0.003 oois 0.015 oun0:0O8 ous0.058 oom0.003 om 0. ! 80 am0.428 ous0.006 Tiled! T~glycerides= 00- O.09fl oun0.033 os "iss .006 - O, 155 -om6 - 0.026 tout og natursl log *Anivevps Decor *Antweq~ vs Decalur "SIBBRS vs 1991 *'1994/95 vs 1997 amozeez220 3M_MN02482223 11779999..00006611 ue 2. Mix Mode Calitics,Sadr vs (SE, Pa 12495l %Confe idece Lis Table 29. Mixed Modal Co~fficic.t l~timalca, Slandard Errors (SF_,), P-Values and 95% Confidence Limits onTain Potcota ekminas of Dk Dri Cars Incug PFOA rdhe rschon ih from Tesling Polenlia] Dclerminanls of Direct Bilimbin~ Change Including PFOA and the Interaction with Nome of Yea ofOlocraionof AverandDectHolsEmpcyes Number of Years of Observation of Anlwerp and Decatur Male Employees cumsew __. - _ ere us Intercep! ron "oo PFOA YonOtscoion "0035 Yeal~ Observalion POA Vemobs 004 PFOA x Yem~ Obs I I Age a oan BMI Drnksay oon Drinks/day Coel'ficien! - 1.753 - 0.0 ! 2 ' - 0.095 - 0.004 0.006 - O.OO3 0,014 [r-- Cigarettes/day Locsin Locatioot* EarPro Entry Perind** Buse Youn Baseline Years Vries Worked Tighe Triglycerides# 0000s - 0.0005 aoe0,083 ous0.345 oon - 0.0008 oom- 0.089 seSE om0.207 oon?0.017 on0.009 IO.(XH I0.{XH oes0.006 ooo 0.020 om0.002 oe0,053 oom0.038 oa0.(304 om0.033 puke p-value <so01 < .0eel a!.47 coon | < .0001 a.27 n. I I P.66 0.50 0.80 n.12 <a< .0001 =n.83 wn.OO9 95% Confidence Limits Loner upp Lower Upper "2161 Ee -2.161 outs om - 0.045 - 1.345 0.02 I om oom -0.113 - O.O77 -o0n2 oun -0.012 0001 oon - 0.001 0.014 oie oo - 0.014 -oms 00s) - 0.026 0.053 ou oo - 0.004 0.003 om oun - 0.022 0.188 om oo 0.271 0.420 ous oun - 0.008 0.OO7 oss -0.155 om - 0.023 Huta |ttntural log "AvnsDecyatur *Anlwerp va Decatur ime ** 1994P)5 vs. 1997 w_woze2226 3M_MN02482224 11779999..00006622 ~..A Company tS Page 63 of 63 ile30. Mod Mot Cocina, Stn Eres5, P-as 45% CotoLins Table 30. Mixed Model Coefficient Estimates, Standard Errars (SE), P-Values and 95% Confidence Limits ffrroommTTestsitinngg PPooitceanttiiaall DDre,tetrmeinranm[sioonffDaDirinrceetcstBiBliilirroubbiinn# CChhaannggee IInncclluuddiinnggTTOOFffaannddtthheeInIntteerraaccttiioonn wwiitthh Ronit Yeuof Ova of Aw Doct i Els Numb~r of Yeara of Observation of Antwerp and Decatur Male Employ~s ost Contrctimi 95% Confidence Limits cen = rae Love . Coefficint SE p-value Lower Upper [I Cire os wor aise 120 Intercept - 1.748 0.205 < .000! - 2.154 - 1.343 or ous - "oon ours TOP " - 0.O13 0.013 .33 - 0.038 0.013 VousOrsion 003 oa0 <a "ons ours Yearn Observation - 0.093 0.010 < .0001 -0.113 - 0.073 LR os a "oon aon TOF x Years Ohm ne oom oom BN Er aoe Age - 0.(}04 0.007 0.003 0.004 -0.011 0.002 .08 - 0.0008 0.014 ma ows oo = amis aoe BMI - 0.003 0.006 .57 -0.015 0.008 Dry aon au om 00st DdnkrJday 0.017 0.020 .39 - 0.022 0.057 CiCgaigraert,~iteless//ddaayy Losin Localion* Ey eae Entry Pedod** Bucivan Baseline Years oes Worked TiTirgihgylyeceerriiddeess~' 0- .00.0000044. a0.074 00.349 om- 0.001 00m - 0.087 10)0.00022 ass0.053 ons0.038 aon0.004 om0.033 .8a4 <Pa M< .0001 n.77 00 -000.00044 ost - 0.031 az0.274 aoe - 0.00g -"00.115522 00.000033 am0.179 aass0.424 00m - 0.022 Airvre rDeec ; ~anatatuurraalllloogg *Antwerp vs Decatur **1994D5 vs 1997 czas 3M_MN02482225 11779999..00006633