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AR RE_ 064s PFOS Medical Surveillance/Epi - | 00013 Interim Report #1 `Epidemiology, 220-3W-05 Medical Department 3M Company St. Paul. MN 55144 Date: June 8, 2000 Title: Determination of Serum Half-Lives of Several Fluorochemicals Study Start Date: Estimated Date of Final Report: IRB Approval Date Protocol Number #0007 IRBEAxpepmrpotvalXX# 9E8x0p9ed5ited June, 2004 14 October 1998 Principal Investigator: Co-investigators: Jean M. Burris, RN, MPH' Geary Olsen, DVM, PhD" Cathy Simpson, RN? Jeffrey Mandel, MD, MPH' Study Director: Study Sponsor Jeffrey Mandel, MD, MPH' Corporate Occupational Medicine Department 32Sa2Mi0n.tC3oPWam-upl0a,5nMyN 55144 1. POacuclu,paMtiNon5a5l1M1e4dicine, Medical Department, 3M Company, 220-3W-05, St. 2 `3AMLD3e5c6a0t9u-r22S0p6ecialty Adhesives and Chemicals Plant, P.O. Box 2206, Decatur, Poet 000014 ABSTRACT Previous estimates regarding the human serum half-life of `perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) ranged between 10001500 days and 365-530 days respectively [Olsen et a. 1999; Ubel et al., 1980). These estimates were based on very few subjects. We are currently in the process of collecting data from 27 retired, fluorochemical production employees in an effort to more `completely estimate the half-life of PFOS and PFOA along with five other fluorochemical analytes. To date, preliminary analyses from three serum collection periods utilizing a one compartment model suggests that the serum half-life of PFOS in these retirees is likely to be four-fold lower than the range of 1000-1500 days that was previously suggested. The serum half-life of PFOA in these retirees appears to be `approximately one year, which is comparable to the estimate suggested by Ubel etal [1980]. Because of the lower limitof quantitation assayed for the other fluorochemical analytes, we believe additional collection periods are necessary before serum half-life calculations can be determined. There are several limitations to the current report, the most important being the paucity of data available to date and the range of the serum levels measured (PFOS range 0.2-2.0ppm: PFOA 0.1-3.1 ppm). We anticipate `completing two additional serum collection cycles before December 2000. Additional data should allow a better assessment of fluorochemical half-lives of all participants in this study. Bupe2 000015 INTRODUCTION Although it has been reported that the serum half-life of perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) in humans may range between 1000-1500 days and 365-530 days respectively [Olsen et al., 1999; Ubel et al., 1980], such estimations have been based on very few subjects. The purpose of this studyistodetermine the serum half-life from a group of Decatur and Cottage Grove retirees for the following fluorochemicals: PFOS, PFOA, perfluorohexanesulfonate (PFHS), N-ethyl perfluorooctanesulfonamidoacetate (PFOSAA), N-methyl `perfluorooctanesulfonamdoacetate (M570), perfluorooctanesulfonamide (PFOSA). and perfluorooctanesulfonamidoacetate (M556). METHODS Twenty-four Decatur retirees and three Cottage Grove retirees havevoluntarily participated in multiple serum sample collection cycles for fluorochemical analysis. The majority of the twenty-seven participants are male, only two are female. All participants are long-term 3M employees. They have worked an average of 28 years in either the DecoarCtotutar ge Grove chemical division. The average age of the participant at the time of the first collectionis 60 years (range: 55-74). The mean number of months from retirement to thestartof the study is 30 months (range: 5-130 months). To dae, there have been three Decatur collection periods: November 1995, June 1999 and November 1999. Cottage Grove retirees have participated in two collection periods: June 1999 and November/December 1999. The next serum sampling is scheduled for May 2000. Participants have received letters informing them of their Poe 000016 individual fluorochemical results as data have become available from thelaboratory. Each participant completes 2 brief medical history questionnaire containing information about current medications,anddisease diagnosis. Responses have been keyed into a SAS dataset and analyzed by JMP software. High-performance liquid chromatography mass spectromelry/mass spectrometry has been utilized to analyze all serum samples (NWB,1999). All samples were analyzed by Northwest Bioanalytical Laboratory, Salt Lake City, Utah with the exception of the M556 and M570 from November 1998. The 3M Environmental Technology and Services Laboratory analyzed these samples. Half-ives were calculated assumaionnge compartment model. A log-linear relationship was used to estimate the serum fluorochemical elimination half-life in participating retirees. In this log linear relationship, th slope ofthe line is related to the elimination constant (-k4) via the equation: Slope = -k(2.303). Once the.elimination constant is calculated, the half-life is determined using the relationship: 1, = 0.693/k, (Medinsky & Klassen, 1996). RESULTS A total of 24 pariipants provided. serum samples for each collection period. A half-life was calculated for each of these individuals for PFOS and PFOA. Except for FHS, half-lives for the other fuorochermicals were not calculated as the majority was below the limit of quantitation by the third collection. Because the assay measurement of PHS was inconsistent (.&, many subsequently collected samples were at higher levels Fae 000017 than initial samples), the calculationof the PFHS half-life was deferred until further blood collections occur. `Table 1 presents the mean, median, range and 95% confidence interval of the `half-lives calculated for those retirees (n=18 for PFOS, n=20 for PFOA) who were judged to have a good fit (* > 0.6) foar linear one compartmental model for PFOS and PFOA. At this time we have not included the other participants in these analyses for two. reasons: 1) lack of three data pointsforsome subjects; and 2) lack of fit of model (i.c.. 0.6). The latter was often due to the fact that the second measurement was higher than the first. At this time we are uncertain whether this may be due to subsequent exposure, biological variation or assay error andlor variation. [Note: We are scheduled to collect 0 more data points by December 2000. By that time we anticipate including all participants in the analysis.] `The range of serum PFOS measured was 0.2 - 2.0 ppm (Table 1). The range of serum PFOA measured was 0.1 - 3.1 ppm. All PFOS serum half-life calculations were of male retirees. Two of the 20 PFOA serum half-life calculations were of female retirees. As can be seen from Table 1, the median serum half life of PFOS was 270days (range 139-640) for the 18 male retirees whose log linear regression model had an r* > 0.6. The median serum half life of PFOA was 344 days for the 20 male and female retirees whose log linear regression model had an r* > 0.6. Restricting the models to 3. 0.8 did not substantially change the half-life calculations for PFOS or PFOA. It should benoted that the highest PFOA half-life calculations were from the two female retirees: 654 and 1308 days. Neither age nor the number of months retired was associated with the serum half-life calculations for PFOS or PFOA. Paes 000018 DISCUSSION "The results from this first interim analysis suggest thatthe serum half-life of PFOS in humans is likely to be four-fold lower than the range of 1000-1500 days that was initially suggested [Olsen et al., 1999]. The serum half-life of PFOA in humans appears to be approximately one year, which is comparable to the estimate suggested by Ubel et al [1980]. Additional collection cycles will further refine these half-life estimates and take into account the retirees who were excluded in this interim report due to lack of fit of the one compartment model. This, of course, assumes a one-compartment model is appropriate at the low ppm serum levels measured in this groupofretirees. Our results from this preliminary interim analysis should be interpreted cautiously due to thepaucityof data available to date. The fourth data point is scheduled to be. collected and analyzed by mid-summer. There are several additional limitations to these: interim data. To date, Cottage Grove retirees have participated in only two serum collection cycles. Thee of the twenty-four Decatur retirees have indicated at each serum collection cycle that they have worked ina consulting capacity in the 3M Decatur plant at some point during the intervening six months. However, their log linear regression `models were considered to be of reasonably good fit (i.c.. r* for PFOS > .80; r* for PFOA 2 57). Four ofthe seven fluorochemical analytes (PFOSAA, PFOSA, M536 and M570) `measured below the lower limit of quantitation for more than 80% of the samples prohibiting a reasonable half-life calculation. At this time we are uncertain why many subsequent PFHS serum levels were higher than the frst measurement. With additional data we hopetodefine half-lives in these compounds although if levels remain below the LLOQ this may not be feasible. Pages 400019 `The next collection period will occur in May 2000 with anticipated results due back from Northwest Bioanalytical by mid-summer. Additional data should allow a better assessment of the half-lives of all retirees. The next interim report should be available by August 2000. Fa ; 000020 REFERENCES OhelpsaetnicGaWn,d BluiprirdisclJinMi,caMlacnhdeemlisJtHr,y ZteosbteslinLRf.luoSreorchuemmipcearlflpuroordouoccttiaonne esumlpfloonyaeteesa.ndJ Occup Env Med 41:1999:799-806. UflbueolroFc,hSeomriceanlsso:naS,prReolaicmihnaDr.y Hreepaolrtt.h sAtamtusInodfHplyagntAwsorskoeJcrs1e9x8p0o:s41e:d5t8o4-589. NWB. Human Quantitative Determination of Serum by LC/MS/MS. 1999. PFOS, PFOSA, Salt Lake City, PFOSAA, Northwest POAA, and PFHS in Bioanalytical (NWB) A Division of NWT Inc. TMoexdiicnoslkoygyMAFi,ftKhlEadaisteionn.CD.199T6o.xiNcoekwinYeotrikc:s (MIcnG)rKalwa-aHsielnl,CDpa(geeds) 1C8a7s-a1r9e5t.t & Doull's Pages 000021 Table 1 Half-Life Summary Data In Days For Those Retirees With Three Collection Periods Whose Log Linear Models Had R? > 0.6 PFOS R206 R208 N__ Mean 18 303 16 303 Median __ Range 270 139.640 259 130640 95% CI of Mean 228378 217-388 PFOA R*>06 20 389 344 R'208 13395 324 109-1308 109-1308 269-509 204-585 Page 9 000022