Document RjD0Xv0r3wxYokMvK1z019dVX

CCoorrpoproart OHcactuphatPiioncssMidicine CCoroporrarte eProdtuctyResponsibly 3M Medica Deparment PO Bcomx s332m20 cr S S. Pu,YMN 351333220 AR226-0023 ='5) 3M PDeertfelruiomrionoacttiaonnoefSuSlefronuimc AEcliidm,inPaetrifolnuHoarlofh-eLaixvaenseosfuAlfmomniocnaiciudmanPderTfoltuaolroOorcgtaannoiacte, Fluorine in Decatur Chemical Plant Retirees `The objectiveofthis study is quanitate the human serum elimination halflife of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA) , perfluoroohexanesulfonate (PFOS) and total organic fluorine (TOF). Blood will be collected biannually from approximately 25 retired 3M Decatur employees for a period of$ years. Upon collection and analysisofthe third sample (baseline, 6 months and then 12 months) and thereafter, an interim draft half-life analysis report will be prepared. 00097; - ` 3MPaCgeomLpfan1y9 PROTOCOL Epidemiology,220-3W-05 Medical Department 3M Company St. Paul, MN 55144 Date: October 14, 1998 TPiEteR:FLDUEOTREOROMCITNAANTOIAOTNEO,FPSEERRFULMUOELRIOMOICNTAATNIEONSUHALLFFO-NLIICVAECSIOD,F AMMONIUM DPEECRAFTLUUORRCOHHEEMXIACNAELSPULLAFNOTNIRCETAICRIEDESA.ND TOTAL ORGANIC FLUORINE IN 3M Study Start Date: Estimated Date of Final Report: IRB Approval Date: Protocol Number # 0007 IRB Approval # 98095 Exempt XX Expedited June, 2004 14 October 1998 Principal Investigator: Jean M. Burris RN, MPH Co-investigators: GJoehanryC.OlSscehnu,mDpVerMt,MPDhD' Cathy Simpson, RN? Jeffrey Mandel, MD, MPH" Study Director: Jeffrey Mandel, MD, MPH" Study Sponsor: Medical Department 3M Company 2203-05 Saint Paul, MN 55144 I. Occupational 55114 Medicine, Medical Department, 3M Company, 220-3W-05, St. Paul, MN 2. 335M6D0e9c-a2t2u06r Specialty Adhesives and Chemicals Plant, P.O. Box 2206, Decatur, AL 000978 - 3MPaCgeom2p0a1n9y ABSTRACT 3M manufactures products which contain chemical compounds, ither as intentional components or residual impurities, that have as parent molecule, perfluorooctane sulfonyl fluoride (POSE), These compounds may be expected to transform metabolically, to an undetermined degree, to PFOS as an end-stage metabolite. Other compounds manufactured by 3M include ammonium perfluorooctanoate (PFOA) and perfluorohexane sulfonic acid (PFHS). These molecules entear numberofproduct applications (e.., surfactants, food packaging additives, polymers) The biological elimination rates of fluorochemicals have been studied in ras, pregnant ats, female rabbits and hamsters. Biological half-lives have been calculated from the studies in rats and dogs. In addition, the half-life of serum total organic fluorine in a fluorochemical worker was estimated using serial collections of serum total organic fluorine. These studies reveal that PFOS and PFOA may persist in the body for prolonged periods, and with continuing exposure, accumulate over time in biological systems. To date, the actual elimination half-life of perfluorooctane sulfonate (PFOS), ammonium perfluorooctanoate (PFOA), perfluorohexane sulfonic acid (PFHS), and total organic fluorine (TOF) in human serum is not completely understood. The objectives of this study are to quantitate the eliminationhalf lfe in human serum of PFOA, PFOS, PFHS, and TOF. These half-lives will be calculated from declines in serum fluorochemical levels in 3M Decatur Chemical Plant Retirees. 000979 . INTRODUCTION 3MPaCgeomJpoafn1y9 3M manufactures products which contain chemical compounds, ither as intentional components or residual impurities. that have as a parent molecule, perfluorooctane sulfons uoride (POSE). These chemicals include: perfluorooctane sulfonate (PFOS), N-ethyl perfluorooctanesulfonamide, N-cthyl perfluorooctanesulfonamido ethanol, N-methyl perfluorooctanesulfonamido ethanol and chemicals derived from it, and the mixture of mono-, diandti [N-<thy! perfluorooctane sulfonamidoethyl] phosphates. There may be other precursors in the workplace, including perfluorohexanesufonyl fluoride (PHSF). These molecules enter a number ofproduct applications (.g., surfactants, food packaging additives, polymers). These. compounds may be expected to transform metabolically, to an undetermined degree, to PFOS (and PFHS) as an end-stage metabolite. Potassium perfluorooctane sulfonate (CF1;0805K*) is ftslf, a surfactant used as a wetting and foaming agent in industrial and commercial processes, (Olsen, et al., 1998) Subchronic studies in rats and primates suggest there may be a potential for cumulative toxicity With PFOS over time with theprimaryeffect related to metabolic wasting. These molecules have long eliminationhalflives in biological systems. Although the mechanism of toxicity is not fully understood, toxicitymaybe due to an effect on peroxisome proliferation, fatty acid metabolism, membrane function, protein synthesisand/ormitochondrial biocnergetics. (Olsen, etal, 1998) The biological elimination rates of luorochemicals have been studied in rats, pregnant ats, female rabbits and hamsters. Biological half-lives have been calculated from the studies in ras and dogs. In addition, the half-life of serum total organic fluorine in a fluorochemical worker 000980 3MPaCgoemspoafn1y5 Was estimated using serial collections of serum total organic fluorine. These studies reveal that PROS and PFOA may persist in the body for prolonged periods, and with continuing.exposure, accumulate over time in biological systems. To date, the actual elimination half-life of perfluorooctane sulfonate (PFOS), ammonium perfluorooctanoate (PFOA), perfluorohexane sulfonic acid (PFHS), and total organic fluorine (TOF) in human serum is not completely understood. The objectives of this study areto quantitate the eliminationhalflife in human serum ofPFOA, PFOS, PFHS, and TOF; these half lives wilbe calculated from declines in serum fluorochemical levels in 3M Decatur Chemical Plant Retirees. This information is necessary in order to: 1) plan the most appropriate periodicity of medical surveillance and 2) guide medical decision making of workers from fluorochemical production facilities when those workers" serum fluorochemical fevels are determined to be unsafely elevated. A benefit of this research will be to understandthe. natural historyoffluorochemical excretion. LITERATUREREVIEW AMMONIUM PERFLUOROOCTANOATE (PFOA or FC-143) Excretion ates of PFOA have been observed in ras, and found to be different by gender and routeof excretion. Following single i.v. doses of "C-FC-143 (carbonyl carbon labeled) in rats, Johnson et al, found that females excreted virtually all the administered 'C within 1 day. Urinary excretion for males was about 50% of the dose by day 6 and 83% by day 36. Fecal '"C excretion for females was 1.5% by3 days and for males was 5.4% by 36 days. (lohnson, et al, 000981 IMPaCgoemspoafn1y9 1980) Rapid urinary excretion of "C following oral doses of VC-FC-143 was also shown to occur in pregnant rats. (Johnson, etal, 1983) Excretion rates vary by species studied. Excretion of radiolabeled PFOA was studied in four species by Dupont in 1988. Excretion as a percentage of administered dose 120 hours after dosing was in the following order; female rar, male and female rabbit and male hamster (> 99%); female hamsier (60%); male rat (39%): male and female mice (21%). (Dupont, 1988) Of noe, the administered dose and routes of exposure and excretion were not specified in this study report. Rats and dogs respond to pharmacologic interventions that change PFOA excretion ate. In male rats administered single i.v. doses of "C-FC-143 (carbonyl carbon labeled) cholestyramine (4% WIW in feed) increased cumulative 15 day fecal C excretion 9.8-fold versus controls. Total *C excretion (feces plus urine) was also enhanced, although less dramatically (84.3%ofdose vs, 71.8% for controls). (Johnson, et al, 1980a; Johnson JD,e al, 1984) There s no difference. between the renal clearances of "*C in male and female dogs either before or after`probenecid. Probenecid significantly reduces PFOA clearance in dogs. Glomerular filtration rates of PFOA were similar in rats and dogs. (Hanhijarvi, et al., 1988) Elimination halflife has been calculated under numerous conditions in ats and dogs. The results show the same differential elimination ate in rats by gender ic. female > male), as well as hlf- life differences by route of exposure and species. Followingasingle oral dose of 'C-FC-143 (carbonyl carbon labeled) in male at, the plasma half-life was 4.8 days. (Johnson, et al, 1979) 000982 3MPaCgoemspoafn1y9 In female rats administered oral or i.v. doses of "C-FC-143 (carbonyl carbon labeled), over 90% ofthe administered dose was recovered in the urine within the first 12 hours. The wholebody elimination half-life of PFOA in male and female rats was 15 days and less than one day, espectively. following a single 4-mg/kg intraperineal dose. (Vanden Heuval, etal, 1991) (Johnson, etal, 1983; Johnson, et al. 1980) The half-life of PFOA in the iver was 60 hours for females and 210 hours for male rat. (Ylinen,e al, 1990) The decreased excretion ate (ic. inereased elimination half-life) in males is seen across at least two species: ras (as above) and dogs. The plasma half-life of PFOA was longer in male dogs (473 to 541 hours) than in females (20210 305 hours). (Hanhijarveit, al., 1988) The elimination halflife appears to be similar in male rats exposed to cither inhalational or dermal exposure. Following repeated inhalation exposures to FC-143 over a two-weekperiod, blood organic fluoride levels in male rats showed a half-life of five to seven days. (Kennedy, et al. 1986) A blood half-life o five to seven days was seen following repeated dermal exposures in male rats. (Kennedy, 1985) Acalculation of the elimination half-life of an organic fluorine species has been reported in the human. The half-life of total serum organic fluorine in a fluorochemical worker who was removed from further exposure was greater than 18 months. This worker hada blood organic fluorine levelof40 pats per millon over the period ofone year. The worker's organic fluorine level rose to 70 partspermillion for no apparent reason. The worker was then removed from the fluorochemical production area and his blood and urine samples were periodically checked for organic fluorine and PFOA over an 18-month period. A total of 18 months transpired before the 000983 | 3M Company worker's blood organic fluorine level had retumed to ts base lineof40 parts per Page7of 19 million. (Ubel, etal. 1980) Other estimates of serum fluorochemical half-lives have been calculated in the one thousand day range. This anecdotal account does not actually rack the serum PFOA level, but rather the serum total organic fluorine (TOF) level. It was found through empirical means that 90% of the blood organic fluorine existed as PFOA. (Ubel, et al. 1980) PERFLUOROOCTANE SULFONIC ACID (PFOS or FC-95) Perfluorooctane sulfonic acid appears to persist in biological systems, being excreted more slowly than PFOA. Single i.v. doses (mean 4.2 mg/kg) of "C-FC-95 and 0.9% NACL were administered to male rats. By 89 daysafter dosing, 30.2%of the administered "C had been excreted in the urine and 12.6% had been excreted in the feces. (Johnson, etal, 1979) Pharmacologic interventions do appear to increase the excretory rateof PFOS. Fecal and total excretion of '"C were markedly increased in male rats administered Cholestyramine (about 2.7 gm/kgperday) and their diet following single iv. dosesof "C-FC95. The results suggest that there was significant enterohepati circulation ofFC-95. (Tohnson, et al. 19802; Johnson, et al, 1989) Much less is known concerning elimination half-life of PFOS than PFOA; only one calculation of the elimination half-life of PFOS has been attempted. The plasma elimination half-life of 'C following single oral administration of '"C-FC-95 (mean dose 4.2 mg/kg) to male rats was 7.5 days. (Johnson, et al. 1979a) 000984  Mandel]. Personal communication. 3MCompany Page8of 19 000985 RESEARCH METHODS 3MPiCgoem9poafn1y9 The overall research design is prospective in nature, obtaining multiple serial blood samples from retirees throughout the course ofa five-year period. We will track the decline in several serum fluorochemical levels in humans. The health outcomes that will be documented in this study are the half-life determinations of serum ammonium perfluorooctanoate (PFOA), perfluorooctane sulfonic acid (PROS), perfluorohexane sulfonic acid (PFHS), and serum total organic fluorine (TOF). High-performance liquid chromatography mass spectrometry/mass spectrometry will be utilized to analyze all serum samples. The accuracy and reliability of this device will be the state of the art at the timeofanalysis. Periodically, split samples from one or two subjects will be utilized to assess reliability of the analysis. Only individuals who have retired from 3M Decatur chemical plant from the ltofJanuary 1995 through the IstofJanuary 1998, will be included in the study. Using information received from the Human Resources Department of 3M Decatur, 34 individuals were identified to have retired during this time period. Of the 34 individuals identified, 7 have previously been enrolled in the fluorochemical medical surveillance program. Four of these individuals participated in the. medical surveillance program in 1994 but not 1997; 3 individuals participated in 1997 only. We will attempt to enroll all 34 retirees into the study. Future retirees will not be enrolled. Serum fluorochemical levels will be drawn every six months. All serum fluorochemical levels will be drawn within a one-month time frame (.c., within one month of March and September). 000986 MTacCoomnptany Retirees will be recruited to the study through first, an introductory letter and second, aphone conversation from the principle investigator or his designee. Subsequent to the follow-up telephone conversation andif the retiree is `willing to enter the study. a written informed consent form (Appendix A) and a medical questionnaire (Appendix B) will be sent to the retireeforhis review. Once the retiree signs the consent form, completes the questionnaire, and returns the documents to the principle investigator, he will be entered into the study and scheduled forblood collection. Participation in the study is voluntary and retirees `may drop out at any time. Blood collection will be scheduled biannually, in April and October (to not conflict withHoliday and summer vacation travel). Letters announcing blood collection dates and times will be sent out to each study subject one month prior to each blood collection month. Retirees will update their medical questionnaire at each blood collection. All blood collections will beperformed under the supervision of the 3M Decatur plant nurse, Cathy. Simpson, RN.`Twored-topped tubes will be obtained from each retiree; the 3M Occupational Medicine Service `methodology for handling and shippingof fluorochemical blood samples will be applied to all blood samples. Samples will be analyzed by the 3M Environmental Laboratoryor its designated contract laboratory. Retirees will receive written reports of their serum fluorochemical levelsfollowing each blood collection cycle. `Two methodsofcalculating the serum fluorochemical half life will be utilized. In the first `method, a one compartment model will be assumed and the formula a= go (0.5) 000987 3PMagCeo1m1p0afn1y9 will be utilized to estimate the half life of elimination for PFOS, PFOA, PFHS, and TOF. The terms q, and go refer to the serum concentrations at time r and time 0, ti the elapsed times 1 is what we seek to solve. The second method will be used to verify the first. It also assumes a one compartment model, Each retiree's fluorochemical levels will be graphed on a log-linear scale as serum fluorochemical vs. elapsed time from to (in months) and entered into a database. Statistical analysis will be performed to determine the best-fit model that describes the slope of the loglinear line. (Appendix C) The slopeofthe log-linear line is related to the elimination constant (+k) through the equation Slope = -k.(2.303) Once the elimination constant is calculated, the halflife can be calculated using the relationship ty, = 0.693/k, Elimination half lives for TOF, PFOS, PFHS, and PFOA will be determined. (Benez, et al. 1985, Medinsky, et al. 1996.) DISCUSSION `There are a number of limitations associated with the study, including: 1. The lack of pre-study serum fluorochemical levels in the majority of retirees, making it impossible to develop baseline levels for the majority of the study group. The 10 values will therefore need to be their first fluorochemical level post-retirement. 000988 3PMagCeo1m2p0afn19y 2. Previous studies have performed serum total organic fluorine levels and not serurm testing specific for serum PFOS or PFOA: comparability with previous work is thereby compromised. 3. Retirees on medications such as colestipol or cholestyramine, which can artificially increase the rate of eliminationoffluorochemicals from the blood will artificially increase the elimination in unpredictable ways, thereby causing an underestimation of the elimination half life in the entire study population. 4. Retirees may unknowingly have medical conditions that will decrease their toxicant elimination rate unpredictably (e.g. renal failure, congestive heart failure, cholelithiasis, etc), thereby causing an inaccurate estimation of te elimination halflife in the entire study population. For these reasons, the study will occur over the protracted period of five years insteadof a shorter time period (ic. three years). As the only human data plotting total organic fluorine suggest plasma elimination half-life of 18 months,a three year study would allow for verification of that estimate since three years wouldbeequal to two half-lives. A five-year study, therefore, should include over three half-livesofelimination, and make it possible to use several years" data to calculate the elimination half life. The overall results collected in this study may be used in publications or in public presentations. Retiree namesorother individual data will not be revealed in any publication or other documentations intended for public examination. Individual results will be communicated only to the retiree. Individual results will be considered confidential information and will not be disclosed to anyone outside of the 3M Medical Department without the retiree's written consent, 000989 3PMagCeo1m3p0afn1y9 Quality assurance will be performed per the guidelines set forth in the standard operating procedure for the creation, review, and approval of 3M epidemiology study protocols. Archiving of study materials, upon completion of the study, will be performed per the standard operating procedure for the creation, auditing, review and approval of 3M epidemiology final reports. The study will be communicated to the retirees, management, and the technical community. Communications totheretirees will be in the formof a letter, which states the retirees various blood fluorochemical levels. These letters will be sent out following each blood draw. Communication to management willbe in the form ofa written document which will undergo the review process as set forth in the standard operating procedure for the creation, auditing, review and approval of 3M epidemiology final reports. The communication to the technical `community will be in the formofascientific paper, which willbesubmitetdo a relevant peer reviewed scientific publication. 000990 REFERENCES 3PMagCeo1m4poafn1y9 1. scOuhllesfmeoinnsatGtreiWe.isn,BmhuaerlrmeiastfoJlluMoo,groyMcaahnnedmdeihcloaJlrHmp,ornaoendsudciLtniRorneZloeabmtepilol.noytAeoensse.epriuJdmeOmlciecvoeullopsgEioncfvpienrvfelsutiograotoicotnanoef clinical iron Med 1998; 2. Johnson JD and Ober RE. Extent cInacr. bSot.n, -1P4auiln, male MN; a1n9d80f.emale rats and rou after a te si of ngl e e xcretion IV dose and tissue of FC-143 distr -4C. ibution of RikeLrabo total ratories, 3: Johnson JD and Conard GJ. Extent and route of excretion of total carbon-14 i aftera single oral doseofammonium 'C-perfluorooctan Rike L pregnant rats Paul, MN; 1983. oate. r aboratories, Inc., St. VmeatnadbeonliHsemu,vaanldJ,elKiumsilniaktiisonB,ofVapenrfRleufoerlogochteamnoMi,c aacnidd.PeJteBrisoocnhRe.m TTiosxsiuceoldi1s9t9r1ib;u6ti:o8n3,.92. 3. DuPont. Ammonium perfluorooctanoate. Toxicity Hazard Information from MSDS; 1988. 6. JchoohlnessotnyrJaDmiannedtOrbeeatrmRenEt.. REinkhearnLcaebdorealtiomriineast,ioInnc.o,fSFtC. -P9au5l-,4MCNa,nd1F9C8-0.143-4C in ratswith 7. J1o4hinnsroantsJaDf,teGriabdsmoinniSsJt,raatnidonOobferamREm.onCihuomle[sCtlyprearmfilnue-oernhanced fecal elimination of carbon- potassium('*C]perfluorooctanesulfonate. ooctanoate or FundAppl Toxicol 1984; 4:972-976. 8. Griffith Ind Hyg FAsDsoacndJL1o9n8g0;JE4.1:5A7n6i-m5a8l3.toxicity studies with ammonium perfluorooctanoate, Am 9. rSHeoanlnalhleivjeeaxlrcdvrieHtAHi,,onYoeldfis.pneeNrnefMlwu,oDrHeoavoaecrltaoannpeomniecnTtaascniiddniBNnieotvhsaecliabeiennacegelnse:TTd.hoegAiarpnrIdompptlohiesceradatt.isopIenc:ifeBoserdyLinafefnerAenCceainndthe Animal Science. Martinus Nijhoff, Dordrecht, 1988. ns borotory 10. DGiislsleirltaantdiFoDn,. U.FloufoMrioncanrebsoontsa,anMidnhneuampaonlihse,alMthN:;st1u9d9i2e.s in an occupational cohort, Ph.D, 11. LJaobhonrsaotnorJieDs,anIndc.O,bSetr. PRaEu.l,AMbNso;rp1t9i7o9n.of FC-143-C in rats after a single oral dose. Riker 12. Johnson JD and Ober RE. Extent and route of excretion of total carbon-14 pregnant rats after aMsNi;ngl1e98o3r.al dose of ammonium "-C perfluorooctanoate. Riker Laboratories, Inc. + St. Paul, 000991 3PMagCeo1m5.p0afn1y9 13. aKmenmnoendiyuGmLp,erJfrl.uHoarlolocGtTan,oaBtriet.telFliunMdR,ChBeammeTosxJicRo,lan19d8C6;he2n4:H1C3.25-I1n3h2al9a.tional toxicity of 14. Kennedy GL, Jr. Dermal 1985; 81:348-355, toxicity of ammonium perfluorooctanoate. Toxicol Appl Pharmacol 15. rYaltianfetnerMs,inKgolejoanAd, sHuabnchhirjoanrivci H, and Peura P. administeation. BDuilslpoEsnivtiiroonnoCfopnetraflmuoTrooxoicctoalno1i9c87a;ci4d:i4n6.th5e.3, 16. fUlbueolroFcAh,emSiocralesn,soanpSreDl,imainndarRyoarecphorDt.E.AmHeaIlntdhHsytgatAusssoofcplJan1t98w0o;rk41e:r5s8e4x-p5o8s9e,d to 17. Johnson JD, Gibson SJ, and Ober RE. Extent and route of excretion and tissue distribution Poafutlo,taMlNc;arb19o7n9-.14 in rats after a single i.v. dose ofFC-95-1C. Riker Laboratories, Inc, St. 18. Johnson JD andOberRE. Laboratories, Inc. St. Paul, Absorption of MN; 1979. FC-95-14C aftear single oral dose. Riker 19. BaenndeetlLimZinaatnidonS.heIin:neGroLoBd.maPnhaGrimalcmoakninAe,tiGcoso:dTmhaendyLnS,amRiaclsl oTfWd,ruagndabMsuorrpatdioFn,.eDdi.stribution, MGaocomdimllaannaPnudblGiislhmianng'CsoTmhpeanPhya,rNmaecwolYoogrikc,B1a9s8i5s.ofTheapeutics, Seventh Edition. 20. BMaesdiicnSsckiyenMcAe oafnPdoiKsloanass,eFnifCtDh.EdTiotiiocno.keKnleataiscesn.CIDn:,CAamradsuerttMaOn,d DaonudllD'osulTloxJi,ceodlitoogrys.: TNheew York, McGraw-Hill, 1996. 000992 Appendix A 3PMagCeo1m6.p0afn1y9 CFOLNUSOERNOTCFHOERMMICFAOLR LCEOVLELLECHTAILFO-NLIOFFEBDLEOTOEDRFMOIRNASTEIROUNM INTRODUCTION yYoouur arentdiryeomuenrtc.olYleoauguaerse wienvrieteidnvtoolpvaerdtiicnipfaltueorinocaheremsiecaarlchprsotduudcytiboeninagt c3oMndDuecctaetdurbypr3ioMr to dOocncautpiantgioonnael rMeedd-itcoipnpeedSteersvtitcuebseroefgabrldoiondg afpluporrooxcihmeamtiecallyse.veYroyusrixpamrotnictihpsatfioorntwhoeunledxtinfviovleve. wyielalrsn.otYboeurusbeldootdo tweisltlfoonrlaynbyeottehsetredsufbosrttahneceasmoorudnitseaansde.kiPnldoefasfeluroervoicehwetmhiiscaclosnsietnctonftoarinms; it pcalraenftunlulrysaenwdilble bseuraevayioluarblqeuetsotpiroonvsiadree yaonuswweitrhedadbdeiftoiroenayloiunmfoarkmeataiodnecaitstihoen to participate. time of your The medical surveillance blood donation. PURPOSE OF STUDY eTlhiemipnuartpeodseforfotmhteheshtuudmyains to determine how body over time. much and what types of fluorochemicals are YSoTuUrDbYloPodRwOilClEbDeUdRraEwSn with one needle stick and require two test tubes. This will occur about ethveerpyrospixermdoantte,hstfiomer,thaendnepxltacfeitvoeryeepaorsr.t A to letter will for blood be sent to collection. you in advance informing you of PTOhTeEoNnTlyIdAisLcRoImfSoKrSt/yBouENmEaFyIfTeeSl is from the needle stick. redness/bruising/swelling in this area after blood collection. You may also have some temporary `BTEheNrEeFwIilTlSbe no gained from this direct study benefit fro will further m h your p elp us articipation understand in this human estxupdoys.urHeoswteoveflru,ortohcehienmfiocramlast.ion i`nYdoiuvriidnudailviredsuualltsrewsiullltsbeascwoenlslidaesretdhecoovnefriadlelntrieaslulitnsfwoirlmlabteiocnoamnmdunwiilclantoetdbteo dyiosucloonsleyd. toYoaunryone outside the 3M Medical Department without your written consent. COMPENSATION If you study, syuofufewrililnjbueryroerfearrmeeddtiocaanlotcohnedrihteiaolnththcaatraepppreoafressstioobnealthate result of participating no cost to you. In the in this event ofa research related injury, compensation will be determined on a case by case basis by 3M. 000993 3PMagCeo1m7p0an1y9 TChOeNFovIerDaEllNTreIsAulLtsIcToYllected in this study may be used in publications or public presentation. eYxoaumrinnataimoen.wilYlounortibnedirveivdueaallerdesiunlatsnywiplulbbleiccaotimomnunoricoathteerddtoocyuomuenotnslyi.nYteonudredinfdoirvipduuballicraetsiuolnts wMieldlicbaelcoDnespiadretrmeednctonwfiitdheonuttiayloiunrfworrimtatteinoncoansnedntw,ill not be disclosed to anyone outside the 3M. ISfUyBoJuEhCavTeRaInGyHquTeSs/tiAoVnAsIaLbAouBtItLhITsYtuOdyFnIowN,FoOrRlMatAerT,oIrOiNn the event ofa research related injury oFroremaenrsgweenrcsyt,ocqounetsatcitonDsr.aJbeofuftreyyouMranridgehlts(i6n5r1e-g7a3r3d-8to67t0hi)sorresJeeaarnchB,uryroius,mRaNy.co(n6t5a1c-t73D7r.-7L8a6r7r)y. Zobel, Chair, 3M Institutional Review Board at 651-733-5181. VOLUNTARY Participation in tPhAsRsTtIuCdyIPisAvToIluOntNarAy.NDReWfuIsTalHtDoRpaArtWicAiLpate will involve no penalty of loss of fboerneafniytsretoaswohni.c`hTyheouianvreestoitghaetrowrimsaeyentsittolpedy.ouYropuaratriceifpraeteiotno iwnitthhidsrsatwudfyrosmhotuhledsittubdeydaettaenmymitniemde bthlaotocdocnotlilneucteidonp,arytoicuipwaitlilornemceaiyvebaecdheetrcikmefnorta$l5t0o.0y0ouars hceoamlpthe.nsFaotliloonwifonrgyeoaucrhtsiemmei-aanndneufaflort, SUBJECT CONSENT tBhyissciognnsienngtthfeorcmo,nsaenndttfhoartmI,hIacveertbiefeynthgaitv1enamadaetquleaatset o1p8poyretaurnsiotlyd.toIacsoknfainrymqutehasttiIohnasvIemraeyad have about this participation in cthoinsssetnutdyf,oramndorthtahteasltluodfy.myI aqluseostcioonnfsirhmavtehabteIeunnadnesrswtearneddtthoemsycospaetiosffamctyion. I tahmatsIiwginlilngretcheiisvceoansceonptyfoofrmthivsolsuingtanreidlyc,onasnedntI dfeosrimr.e tIoupnadretrisctipaantdetihnattIhewisltludrye.ceIiuvnedaercshteacnkdfor $50.00 immediately following each semi-annual collection of my blood. --_-- Signature --_-- Printed Name W--i_t--ness -- DaTtEe -------- 000994 Appendix B MEDICAL HISTORY QUESTIONNAIRE Please list the names of the ALL the medications you take at least once a day. 3PMagCeo18m.0pan1y9 Please circle the conditions you now suffer from or have suffered from in thelastthree years. Kidney Failure Gall Bladder Disease: Hepatitis Jaundice Congestive Heart Failure Liver Disease Inflammatory Bowel Disease Crohn's Disease Pemicious Anemia 000995 co AppendiCx 3PMagCeo1m9p0afn1y9 Exampleof a log-linear plot that will be used to estimate the serum fluorochemical elimination `halflife in Decatur retirees. ole OLi Slope = -k2.303 i] !i LI i nd Tie 000996