Document VJaa5EmJRdr441Z2jbNa7Zz4N

mmeee.. Nespee AR726-C033 3M Determination of Serum Fluorochemical Levels in Sumitomo 3M Employees Ninety-four Sumitomo 3M employees participated in a voluntary, cross-sectional serum fluorochemical assessment. Three groupsof employees were examined. Sagamihara Plant production employees (n = 32) were involved in the inspection and converting of finished goods. Sagamihara Plant management employees (n = 32) were involved in primarily non-production work activities. Tokyo Head Office employees (n = 32) are generally not occupationally-exposed to fluorochemicals. All but twoof the 94 participants were male employees. Among the Sagamihara Plant production employees, the highest serum perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA) and perfluorohexanesulfonate (PFHS) levels were 0.628 ppm, 3.6 ppm and 0.117 ppm, respectively. Serum levels for the Sagamihara Plant Management and Tokyo Head Office were, on average, under 0.01 ppm (PFOS), 0.03 ppb (PFOA) and 0.025 ppm (PEHS)Serum levels of PFOS for Sagamihara Plant management and Tokyo Head Office employees were similar to levels seen in a small group of US 3M Center employees who `were not occupationally exposed to PFOS. Serum PFOS levels of Sagamihara Plant production employees were below thoseofworkers at the 3M Antwerp and Decatur 001693 OccupationPalRMOedTicOiCneO, L220-3W-05 Medi3cMalCDoemppaarntyment St. Paul, MN 55144 Date: 9 January 1999 Title: DETERMINATION EMPLOYEES OF SERUM FLUOROCHEMICAL LEVELS 3M SUMITOMO SSttaurdtyDPartoet:ocol Number: EPI-0008 Estimated Date of Final Report: IRB Approval Date: 1/20/99 IRB Approval Exempt Expedited Principal Investigator: Co-investigators: JJeoahnn BCu,rrSicsh,uRmpNe,rtM,SM..}D., MPH! JGeefafrreyyOMlasnedne,lD,.VM..MD.,, PMhP..DH.!.! Study Director: Jeffrey Mandel, M.D., MPH. Study Sponsor: 33MM CMeodmipcaanlyDepartment S2a2i0nt-3PaWu-l,0M5 N 55144 1. Occupational Medicine, Paul, MN 55114 Medical Department, 3M Company, 220-3W-05, St. | 001694 PROTOCOL FOR SERUM FLUOROCHEMICALDETERMINATION IN 3M SUMITOMO EMPLOYEES ABSTRACT 3M manufactures products which contain chemical compounds, either as intentional components or residual impurities, that have as a parent molecule, perfluorooctane. sulfonyl fluoride (POS. These compounds may be expected to transform metabolically, 10.an undetermined degree, to PFOS as an end-stage metabolite. Another compound manufactured by 3M includes ammonium perfluorooctanoate (PFOA). These molecules enter a number of product applications (e.g. surfactants, food packaging additives, polymers). `3M Sumitomo inJapan processes manyofthese compounds into products for distribution and sale. Fluorochemical applicatioarnes also investigated in 3M Sumitomo laboratories. The purpooftshies study is to measure serum fluorochemical levels in selected `employees of the 3M Sumitomo population. The specific fluorochemicals to be measured include perfluorooctancic acid (PFOA) and perfluorooctane sulfonate (PFOS). 001695 RESEARCH METHODS Approximately 110 employees will be invited to participate in this nonrandomized cross-sectional study; all subjects are volunteers. Thirty individuals are involved in the processing and formulation various forms of pure fluorochemicals into finished products for distribution throughout Asia. Approximately 20 individuals are actively involved in laboratory fluorochemical research. Approximately 60 managerial employees, considered non-occupationally exposed to fluorochemicals, will also be. invited to participate. Information concerning respondents' age, gender, and occupation willbe obtained from 3M Sumitomo Human Resources for review with the serum fluorochemical results. `The study duration wil beapproximatelythree weeks, Written informed consent wil be obtained from all studysubjectsin Japanese (Appendix A). Eachsubjectwill be involved for about 15 ~ 20 minutes and will donate two10ml. blood sample. Should any employee complications arise as a consequence of phlebotomy, physicians associated with 3MSumitomowill treat ther. . Once the blood samples are obtained, they will be frozen in dry ice and sent by 3M Center in Saint Paul via Federal Express. At the 3M Center Medical Clinic, serum will be separated by centrifugation and sent to the 3M Environmental Laboratory for analysis. Standard electrospray HPLC MS/MS will be used to determine the fluorochemical content of all serum samples. Serum will be analyzed for the presence and amount of PFOA and PFOS. Results will be reported to the Principal Investigationr t parts per billion (ppb). The Principal Investigator will inform 3M Sumitomo employees 001696 of their PFOS and PFOA levels aftr results and abrief explanation are be translated into Japanese. The Principal Investigator will forward the results to the appropriate Co-investigator for statistical analysis. Descriptive statistics performed will include group mean fluorochemical level and standard deviation of the mean, and range of serum fiuorochemical levels. Correlation and regression analyses will be performed utilizing information obtained concerning age,gender, and occupation. RESULTS Aformal repoofrthte research findings, including data analysis, will be submitted to the 3M Medical Director and Institutional Review Board at the conclusionofthe study. Theprotocol will be amended only with approvalof the 3M Institutional Review Board. 001697 APPENDIX A ~ CONSENT FORM CONSENT FORM FOR COLLELECVTEIL ONDEOTFEBRMLIONOADTIFOORN SERUM FLUOROCHEMICA mIYaoNnuTaRagnOedDmUeyConutTrIacOtoN3llMeaSguumesitaormeoi.nvYooluveadreininfvliutoerdoctohepmairctiaclippartoeduicntaiorne,seraersecahrscthu,doyrbeing icpalorlntdioucncilptyaetdbieobnytews3otMeudlCdfoorripntvohorelavatemedoOoucnncatutpiPanFtgOitAonw,aoPlFrMOeeSdd,-itaconipdpneeidtsrtepegrsaterctduuirbnsegosrfoslfuitbolcrooooncdth.aeimYniosc;uarltsb,wlioYlolodu.nsot cpbaaerrteuifscueildplayttoea.ntedsAtb3feoMrsuaSrnueymyioottuhoremrqouseursbetspiortneassnecanertseatoiarvndesiwsweiealrlseeb.debPaelvfeaoairsleeabryleoevutiomewaprktohevisiadcdeoenycsioesunitowniftfohorm additional information at the time of your biood donation. TaPchUieRdPp(OuPrSFpOEoAsO)e,FopfSeTrtfhUleDusYotruodoyctiastnoedseutlfeornmaiten,eatnhde pitrsepsreenccuersaonrdsaimnoyuonutr osferpuemr.fluorooctanoic aSYoTounUreD-bYtlioPmoRedObwCliolEloDdbUedRodEnarStaiwonn.with one needle stick and require two test tubes. This will be TdPihOseTcoErliNosTrkaIstAoiLfonvRefInrSioKpmSu/nbBclEteNueErdFeiIniTgnSculnuddeerptahiensokinn,neaenddlediisncseormtfioornt, bflreoemdibnlgooudndcleortttihnge.ski, (hematoma) if bleeding under the skin occurs. TiBnhEfeNorEreFmIawTtiSilonbeganiondeidrefcrtobmentehifsitstfurdoymwyiolurfupratrhteircihpealtpiounsiunntdheirsssttaundyd.huHomwaenveerxp,otshueres fo cifnlofumoomrruomncahitecimoaintceaadlnsdt.owyYiooluunroontilnybd.eivdYiidosuucalrloisreneddstiulvotiasdnuaayslownreeelsluolautstsstwihidelelotvbheeerac3lolMnsriMesdeuedlritecsdawlciloDlnefbipedaernttmiaelnt without your written consent. HICfoOyMofuiPnEasnuNcfSifaeAlrTicInoOjmuNpreynosrataimoendiwiclallbceonfdoirttihocnotmhiantgaapspaearressutlot boef ptahretriecsiuplattoinfgpairnttihciispsattuidnyg. ciIannsttehhiebsaessvitesundbtyyo,fy3oMau.rweislelarbcehrreefleartreedditnojaurnyo,tchoemrpheenaslathticoanrewiplrlobfeesdsieotnearlmaitnendoocnosat tcoasyeobuy 001698 mpCrOeeNseFonIvteDartEailNolTn.IreAsYLuolItuTsrYcnolalmeectewdillinntohtisbestruedvyeamlaeyd bine aunsyedpuibnlpiucbaltiicoantioornostohrerpudboleisc oJintotebonendledyid.sfcYolorousperudbiltniodciaavntiiydoounanleexroaeumstuislnitadsteiwoitnhl.e b3YeMocuoMrnesidiniddceiarvlieddDucaeolpnafrreistduemlneltnsitawliwliilntbfheoorucmtaoytomiomn uannmgeenwtsilslto consent. ur writen rSeUlyBaotJueEdChiaTnvjReuIraGynHyoTrSqe/umeAseVtrAigIoeLnnsAcBayIb,LocIuotTnYttahOceFtstDIurN.dFyJOenfRofMwre,AyToMIraOlnaNdteerl, o(r65in1.th7e33e.ve5n6t70o)ofarresearch uBusrrirse,seRaNr.ch,(6y5o1u-7m5a7y-7c8o6nt7a)c.t 651-733-5181. For Dr. LaanrsrwyrZsobteol,quCehsatiiro,nsSaMboIunsttyitouutriornisg]hRtsevtinerJweegabanorrd etoat lVPoaOsrstLoiUfciNbpeTantAeifRoinYtsiPn1A0tRhwTishIiCscIhPtyAioTsIuuvOaoNrleuAdonNtthaDyeryrW.wIiTsReeHfDeunsRtailAtlWteoAd.pLarYtoiuciapraetefwrieleltionrveofluvseen1ogp `penalty of dfeortearnmyirneeadsotnha.t Tchonetiinnvueesdtipgaarttoircmipaaytisotnompayoyubrepdaerttriicmipeanttiaolntionytohuisrsheuall,Shaerrtiicipate ahBSayUvBseJiEgrnCeiaTndgCtOthhiNseSccEoonNnssTeenntt ffoorrmm,,Iancderttihfayt tIhhaatvIeabmeeant lgeiavsetn1a8dyeeqaurastoelod.ppI coornftiurnmaithsatik| hjaunnvydeeqrbuseetseatnnidoanntshsewI emsrcaeoydpehtoaofvmemyaybsaoptauirtstfitahcciitspiaocnto.inosn1eainntmftoshriisgmnsiotnurgdytt,hhieasnscdtountdhysa.etnta1lalfloosrofm;mvcooylnufqniutreamsrttiihloayntsa| pc1aodrnetssieicrnietpatftooirpnmagr.itniIctuihpniadstesertisuntdyat.nhde stthuadtyI.wiIlulnndoetrrsetcaenidvethaanty fwiinlalnrceicaelicvoemp6eonpsayotifohnifsoirg,nendd Signature Date Printed Name, Witness 001699 --_-- Date: September 3, 1999 Final Report Epidemiology, 220-3W-05 Medical Department 3M Company LSt. PPaul, MMNNS5S51I444 Title: Determination of Serum Fluorochemical Levels in Sumitomo 3M Employees Study Start Date: March, 1999 IRB Approval Date: January 20, 1999 Principal Investigator: Co-Investigators: Jean Burris, RN, MPH' Geary W. Olsen, DVM, PhD" Jeffrey H. Mandel, MD, MPH! John C. Schumpert, MD, MPH! Study Director: Study Sponsor: Jeffrey H. Mandel MD, MPH 33MM MCeodmipcaalnyDepartment 2203-05 St. Paul, MN 55144 L. Occupational MN 55114 Medicine, Medical Department, 3M Company, 220-3W-05, St. Paul, 001700 Introduction 3M manufactures products, which contain chemical compounds, either as intentional components or as manufacturing residuals, which, have as a parent molecule, perfluorooctane sulfonyl fluoride (POS). These compounds may be expected to transform metabolically, o an undetermined degree, to PFOS as an end-stage metabolite Another compound manufactured by 3M includes ammonium perfluorooctanoate (POAA). These compounds enter a number of product applications (c.g., surfactants, polymers, and food packaging additives). Sumitomo 3M in Japan processes many of these compounds into products such as fire protection products and surface protection products for distribution and sale. Other potential fluorochemical applications are also investigated in Sumitomo 3M laboratories. Purpose `The purpose of this investigation was to estimate potential fluorochemical exposure to Sumitomo 3M employees, using the serum component of blood as an exposure measure. Methods 94 Sumitomo 3M employees participated in a voluntary, cross-sectional, fluorochemical Serum measurement. It i assumed that serum fluorochemicals measured represent occupational exposures, although we have not included fluorochemical air measurements from the Sagamihara plant in this assessment. Employees ranged in age from 31-67. `These employees came from threejob exposure groups as described in a personal `communication with S. Yamana. These groups were defined as: Sagamihara Plant production employees (n=32) involved in the inspection and converting of finished goods. These workers were also involved with compounding, using chemicals made from POSF, and formulation of products containing additional fluorochemicals. The next group included Sagamihara Plant management employees (n=32) working primarily atthe same site as the Sagamihara Plant production employees. There was no regular handling of fluorochemmicals in their usual work capacities. The last group included management employees from the Tokyo Head Office who are generally not 001701 `occupationally exposed to fluorochemicals (n=30). All but two of the 94 participants were male employees Each study participant donated two 10 cc tubes of blood. Blood was collected between March 17 and 19, 1999. The blood was centrifuged twice for 15 minutes at 3000 RPM immediately after drawing to obtain serum. The serum was shipped frozen to the 3M Medical Clinic in St. Paul, Minnesota where it was distributed to the appropriate laboratories for analysis. Following analyses, individuals were notified of their results by confidential letter. Laboratory Analysis Individual serum was analyzed for seven fluorochemical compounds using high-pressure liquid chromatography electrospray tandem mass spectrometry measurement (LC/MS/MS). Northwest Bioanalytical (NWB) Salt Lake City, Utah analyzed five of the fluorochemical compounds. They analyzed the serumforperfluorooctane sulfonate. (PFOS), perfluorooctane sulfonamide (PFOSA), n-ethyl perfluorooctanesulfonamido acetate (PFOSAA), perfluorooctanate (POAA), and perfluorohexane sulfonate (PFHS). NWA conducts all studies within the guidelines of the US FDA Good Laboratory Practice, the OECD Principles of Good Laboratory Practice and the Japanese MHW. Good Laboratory Practice Standard Ordinance for Nonclinical Laboratory Studies on the. Safety of Drugs (Ordinance No. 21, PAB Notification No. 424). The 3M Environmental Technology and Services Laboratory analyzed the serum for perfluorooctanesulfonamido acetate (M56) and n-methyl perfluorooctane sulfonamido acetate (M570). Northwest Bioanalytical's validated LC/MS/MS provided a lower limit of quantitation (LLOQ) in parts per million (ppm) of 0.0314 (PFOS), 0.001 (PFOSA), 0.00223 (PFOSAA), 0.00527 (POAA),and0.00261 (PFHS). 3M Environmental Technology & Services Laboratory provided a lower limit of `quantitation (LLOQ) in parts per million (ppm) for MSS6 that ranged from 0.01-0.025 `ppm, and M570 that ranged from 0.01-0.05 ppm. 001702 Data Analysis, Data were analyzed using standard statistical software programs. Comparisons of arithmetic means was done using student's test. A statistically significant difference in one of the means was set at p = 05 or less. Results PFOS Table | summarizes the serum PFOS, POAA and PHS values for the Sumitomo 3M employees. Twenty-four PFOS values were reported below the lower limit of quantitation (0.0314 ppm). Twelve (38%) of 32 Sagamihara plant management employees had values less than the lower limit of quantitation (LLOQ). The range of PFOS for the remaining 20 employees in this group was 0.032-0.057 ppm. Descriptive statistics and t-tests were calculated using the LLOQ value (0.0314 ppm) for those individuals who had values below the LLOQ Forty percent of the Tokyo Head Office employees had PFOS values <LLOQ. The range of measurable PFOS was 0.033-0.0967 ppm for the remaining employees. The remaining statistics were calculated using the LLOQ value (0.0314 ppm). PFOS was `quantifiable in all 32 Sagamihara Production employees. The arithmetic mean value was 0.135 ppm (range: 0.0475-0.628 ppm) which was significantly different (p<0.05) than the `mean PFOS value for employees in both the Tokyo Head Office and Sagamihara Plant managers group. POAA As per Table 1 the lower limit of quantitation for POAA was 0.00527 ppm. Three of the 94 employees had a POAA value reported less than the lower limit of quantitation. One of these employees was from the Sagamihara Plant management and two were from the Tokyo Head Office. The midpoint between zero and the LLOQ was utilized in calculating the statistics for POAA. The mean POAA value for the Sagamihara Production employees was 0.201 ppm that was significantly different (p<0.05) than the mean POAA values for the Tokyo Head Office and Sagamihara Plant managers group. 001703 PEHS As per Table 1 fourteen percentof employees had PFHS values reported <LLOQ (0.00261 ppm). Ten were employees from the Sagamihara plant management group and three were from the Tokyo Head Office. The midpoint between zero and the LLOQ (0.0013 ppm) was utilized to calculate the univariate statistics for the Sagamihara plant `management group. The arithmetic mean value for this group was 0.00626 ppm with a range of 0.0027-0.0241 ppm. Again, the arithmetic mean PFHS (0.020 ppm) for the Sagamihara Production employees was significantly different than the other exposure groups (p<0.05). PFOSAA, PEOSA `We chose not to statistically analyze PFOSAA and PFOSA because of the large number of employees who had senim values reported below the lower limitof quantitation. Eighty-four percent of all Sumitomo 3M employees had PFOSAA values reported below the lower limitof quantitation (0.00223 ppm). Fifteen of94 employees had a PFOSAA. value reported between 0.00247 and 0.0133 ppm. `The lower limit ofquantitation for PFOSAis 0.001 ppm. Four of the 94 employees had a detectable level of PFOSA. These values ranged from 0.00241-0.0068 ppm. M556, M570 `We chose not to statisticallyanalyzeM556 and M570 because of the large number of employees who had serum values reported below the lower limit of quantitation. Only one Sumitomo 3M employee had a quantifiable level of M556 (0.0032 ppm). Ninety-three percent of all employees had MS70 values reported below the lower limit of quantitation. The average M570 value for the seven employees with quantifiable levels of M570 was 0.007 ppm. The range was 0.00311-0.0144 ppm. 001704 Discussion Ninety-four Sumitomo 3M employees participated ina voluntary, cross-sectional serum fluorochemical assessment. Thirty-two employees were identified as Sagamihara Plant production employees involved in the inspection and converting of finished goods, doing some compounding, using chemicals made from POSF, and doing some formulation of products containing other fluorochemicals. Thirty-two employees were described as Sagamihara Plant management employees who work primarily at the same site as the Sagamihara Plant production employees. Finally, 30 management employees from the. `Tokyo Head Office who are not usually exposed to manufactured fluorochemicals participated in the assessment. Employees described as having the highest exposure to POSF chemistry had PFOS levels three times higher than employees in both the Sagamihara plant management group and the Tokyo Head Office. The mean serum PFOS level for plant production employees was 0.135 ppm (range: 0.0475-0.628 ppm) compared to mean PFOS valuesof 0.0403 PPm (range: 0.0319-0.0566 ppm) for Sagamihara Plant management employees and mean PFOS of 0.0523 ppm (range 0.033-0.0967 ppm) for Tokyo Head Office employees. Serum fluorochemical levels in Sumitomo 3M employees can be compared to serum levels recently measured in 3M employees occupationally exposed to fluorochemicals in facilities outsideof Japan (Table 2). Serum fluorochemical levels were measured in employees at 3M Decatur Alabama as part of an on going medical monitoring program in 1997. Since 1980 the Decatur plant is the primary locationofthe production of certain fluorochemicals that may ultimately be measured in the serum as PFOS. Arithmetic mean serum PFOS levels in 1997 were 1.96 ppm (range 0.10-9.93 ppm)." Outside the United States 3M manufactures PFOS related materials at its Antwerp, Belgium facility. Arithmetic mean serum PFOS levels in Antwerp employees in 1997 were 1.5 ppm (range: 0.1-4.8 ppm).' In 1998 31 3M Center employees in St. Paul, Minnesota were tested for serum PFOS. All were corporate staff or division managers. None had worked in fluorochemical 001705 production. Employees ranged in age from 37-62 years. Arithmetic mean PFOS was 0.047 ppm (range: 0.028-0.096 ppm). Both the arithmetic mean and range for this group are similar to the arithmetic mean and range PFOS of the Sagamihara Plant management (mean=0.0403; range=0.0319-0.0566) and Tokyo Head Office (mean=0.0523; range=0.033-0.0967). Conclusion Ninety-four Sumitomo 3M employees participated in a voluntary, cross-sectional serum fluorochemical assessment. Serum levels were highest for Sagamihara Production employees. This is the same group where there is potential for greater occupational fluorochemical exposure, although industrial hygiene measurements were not partofthis assessment. Serum levels of PFOS for Sagamihara Plant management and Tokyo Head Office employees were similar to levels seen in a small group of US 3M Center employees who were not occupationally exposed to PFOS. PFOS levels are well below levels found in workers at plant sites where POSF chemistries are produced (Decatur, Antwerp). None of these levels would be expected to be associated with health problems based on our current understanding of these compounds 001706 Table 1 Serum Fluorochemical Levels in Sumitomo 3M Employees PFOS (ppm) LLOQ=0.0314 || PLLOOAQA=0(.p0p0m5)27||LPLFOHQS=0(.pp0m0)261 SagamiharaPlant --TMean Production Employees T0035 0.0919 [0201 0.0496 Too | Jooio N=32 06265 0.0283 [Range [00475-0628 0.0189-3.600 0.00287-0.117 Sagamihara Plant [Mean [0.0403 00117 0.00626 MaN=n3a2gement [Sbey 000.0037851 100095 Toooss | TokyoHead Office [Range [0.0319-0.0566__| 0.00264-0.059 | 0.0027-0.0241 [Mean 100523 [00126 [oooss | N=30 [Median 10.046 1001195 [00038 [Subev T00IL 000618 [Range 0.033-0.0967 0.00264-0.029 | 0.0013-0.016 Table 2 Mean Serum PFOS Levels 3M Center | Decatur 1998 1997 N=31 N=g4 | Antwerp 1997 N=65 | Sagamihara | Sagamihara|Tokyo Head Production | Plant Mgmt | Office N=32 N=32 N=30 | (ppm) [P om 001707 REFERENCES Olsen GW, Burris JM, Mandel JH, Zobel LR. Serum perfluorooctane sulfonate and hepatic and lipid clinical chemistry tests in fluorochemical production employees. J Occup Env Med (1999, in press). 001708