Document Rjj4k2L0nO8B148EbEOq5q6eV

R a - H - I3S"^ Page 1 FINAL REPORT Epidemiology, 220-3W-05 Medical Department 3M Company St. Paul. MN 55144 Date: June 17,2003 Title: Descriptive Analysis o f Serum Fluorochemical Concentrations from Cottage Grove Employee Participants o f the 2002 Medical Surveillance Program Protocol Number: N/A IRB Approval: N/A Principal Investigator: Co-investigators: Geary W. Olsen, D.V.M., Ph.D .1 Jeffrey H. Mandel, M .D.1 Study Director: Jeffrey H. Mandel, M .D.1 1. Corporate Occupational Medicine, Medical Department, 3M Company, Mail Stop 220-3W-05, St. Paul, MN 55144. 00005*7 Page 2 ABSTRACT In December 2002, 38 Cottage Grove employees voluntarily participated in the fluorochemical medical surveillance program. As part of this program, a blood sample was collected from each participating employee for the determination o f two serum fluorochemicals: perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS). The serum PFOA concentrations ranged from 0.07 to 32.6 ppm with a mean (arithmetic) o f 4.325 ppm (95% Cl 2.025 - 6.624) and a geometric mean o f 1.665 ppm (95% Cl 1.019 2.720). Eleven participants' serum PFOA concentrations exceeded the Biologic Limit Value o f 5 ppm for PFOA. Serum PFOS concentrations ranged from 0.050 to 1.170 ppm with a mean of 0.334 ppm (95% Cl 0.245 - 0.422) and a geometric mean of 0.254 ppm (95% Cl 0.198 - 0.327). The differences between the employees' 2002 PFOA and PFOS serum concentrations and their most recent prior measurements (collected since 2000) resulted in a mean decline o f approximately 0.2 ppm for each compound. A cautious interpretation is warranted o f any trend in serum concentrations because potential occupational exposure information was not incorporated in the analyses nor was time since last analysis. oooof INTRODUCTION Page 3 In December 2002, the fluorochemical medical surveillance program was offered to employees at the 3M Cottage Grove (Minnesota) chemical manufacturing plant. Results have been reported elsewhere for previous fluorochemical medical surveillance programs at the Cottage Grove manufacturing plant (Gilliland and Mandel 1996; Olsen et al. 1998; 2000; 2003b) as well as the 3M Decatur (Alabama) (Olsen et al. 1999; 2001a; 2003a) and the 3M Antwerp (Belgium) fluorochemical manufacturing plants (Olsen et al. 1999; 2001b; 2003a). There were fewer participants in the 2002 Cottage Grove fluorochemical medical surveillance program than in previous examination years (1994, 1997,2000) at this manufacturing site. This was likely due to the fact that the 2002 fluorochemical medical program was offered after the company's announcement to cease production of perfluorooctanyl-related materials, including perfluorooctanesulfonate and perfluorooctanoic acid (ammonium salt). The purpose o f this study is to report the serum fluorochemical concentrations that were measured in 2002 and compare the participants' results with their most recent previous serum concentrations. METHODS The fluorochemical medical surveillance program is offered to employees at the Decatur manufacturing site on a periodic basis. Participation is voluntary. As part o f the 2002 program, a blood sample was collected from each participating employee for determination o f two serum fluorochemicals. These fluorochemicals were perfluorooctanoate (PFOA, C7F15COO) and perfluorooctanesulfonate (PFOS, CgFnSCY). 00005* Page 4 These two fluorochemicals were determined by high performance liquid chromatography electrospray tandem mass spectrometry methods (Hansen et al. 2001). Analyses were conducted at Tandem Labs (Salt Lake City, UT) using validated methods that have been reported elsewhere (Tandem Labs 1999; 2001a; 2001b). Fluorochemical concentrations were measured in pg/mL and reported as parts per million (ppm). RESULTS The 38 Cottage Grove employee participants o f the 2002 fluorochemical medical surveillance program had a distribution o f serum PFOA and PFOS concentrations comparable to the results obtained from prior serum fluorochemical assessments for this manufacturing facility (Olsen et al. 2000; 2003c). Several subjects have contributed to multiple reports. Serum PFOA concentrations ranged from 0.070 to 32.6 ppm (Figure 1) with a mean (arithmetic) o f 4.325 ppm (95% Cl 2.025 - 6.624). Because the concentrations were skewed, a geometric mean was also calculated for PFOA (1.665 ppm, 95% Cl 1.019 - 2.720) which was comparable to the median value o f 1.6 ppm. Twenty-six participants had a prior serum PFOA concentration (analyzed since 2000) whose mean was 6.255 ppm (95% Cl 2.965 - 9.545) and median 3.345 ppm (Figure 2). Their mean 2002 serum PFOA concentration was 6.056 ppm (95% Cl 2.87 - 9.249) and median was 3.180 ppm. The mean difference was a decline of (-) 0.199 ppm PFOA [95% Cl (-0.629) - 0.231, p < .18]. The 38 participants had serum PFOS concentrations ranging from 0.050 to 1.170 ppm (Figure 3) with a mean of 0.334 ppm (95% Cl 0.245 - 0.422) and a geometric mean 000060 Page 5 o f 0.254 ppm (95% Cl 0.198 - 0.327). The median PFOS value was 0.280 ppm. Twentytwo participants had a recent, prior serum PFOS concentration (analyzed since 2000) (Figure 4) whose mean was 0.616 ppm (95% Cl 0.352 - 0.880) and median was 0.390 ppm. These 22 employees' mean 2002 serum PFOA concentration was 0.423 ppm (95% Cl 0.287 - 0.559) with a median value o f 0.310 ppm. The mean difference between these 22 employees' 2002 PFOS concentration and their most recent prior PFOS concentration was a decline o f (-) 0.193 ppm PFOS [95% Cl (-0.351) - (-0.034), p < .01]. DISCUSSION Because potential exposure to PFOA as well as perfluorooctanesulfonyl fluoride (POSF)-related materials occurred between the prior fluorochemical medical surveillance program (2000) and the present one, it is not possible to determine whether the modest decline in serum PFOA and PFOS concentrations is the result of serum elimination and/or reduced opportunity for potential workplace exposure. An ongoing study is examining the serum half-life o f elimination for PFOA and PFOS among 27 retirees followed for 5 years at the Decatur and Cottage Grove manufacturing sites. Results from this investigation should be available in 2004. Presently, the estimated serum half-life of elimination for PFOA and PFOS are 4.4 years (SD = 3.5) and 8.7 years (SD = 6.1) respectively (Burris et al. 2002). These estimates, however, are based on only 9 o f these retirees followed for 18 months. Eleven participants had serum PFOA concentrations that were greater than the Biologic Limit Value (BLV). The purpose for the PFOA BLV program is explained, in detail, elsewhere (3M Company 2001). Basically, 3M established the BLV (5 ppm serum 000061 PFOA) to represent the best estimate o f a level o f a chemical substance or its metabolite in a biological fluid that if present, even on a chronic basis, would not be expected to pose, or correlate with, a significant risk of adverse health effects to the w orkers). By establishing this BLV at 5 ppm for PFOA, the 3M exposure guideline committee did not intend to imply that serum levels o f PFOA greater than the BLV immediately impose a significant risk of adverse health effects. However, if an employee's serum PFOA level either meets or exceeds the BLV, it should be understood that corrective actions (which may include temporary removal from the immediate work area) may need to be applied, on a case-by-case basis, at the direction o f 3M Corporate Occupational Medicine. Implementation of the BLV program by 3M Corporate Occupational Medicine did not allow for employees with serum PFOA concentrations > 1 0 ppm to be directly engaged in the production o f PFOA (Olsen et al. 2003c). Cottage Grove employees' serum PFOA concentrations have not been associated with adverse hepatic clinical chemistry enzymes, cholesterol, lipoproteins, plasma cholecystokinin, reproductive hormones or thyroid hormones (Gilliland and Mandel 1996; Olsen et al. 1998; 2000; 2003c). There are several limitations to the analyses presented in this report. The results arise from a small subset o f employees who voluntarily participated in the 2002 Cottage Grove fluorochemical medical surveillance program. The number o f employees in the 2002 fluorochemical medical surveillance program is 75 percent less than those who participated in the 2000 fluorochemical medical surveillance program. Attrition of employees due to production cessation o f PFOA and POSF-related materials occurred between 2000 and 2002. Unlike the 2000 Cottage Grove fluorochemical medical surveillance program, employee interview data were not collected in 2002 to provide an 000062 Page 7 estimate o f exposure to POSF-related production areas for these workers. Therefore, it was not possible to associate serum fluorochemical concentrations to potential workplace exposures in the 2000-2002 time period. Knowledge regarding the serum elimination half-life o f these fluorochemicals remains sparse. Actual time was not taken into account in the comparison o f the most recent prior test results compared to the 2002 serum fluorochemical measurements. As a consequence o f these limitations, there needs to be cautious interpretation o f any trend analysis o f the serum fluorochemical concentrations o f the 38 Cottage Grove employees who participated in the 2002 fluorochemical medical surveillance program. 000063 Page 8 REFERENCES Burris JM, Lundberg JK, Olsen G, Simpson C, Mandel J. 2002. Determination of serum half-lives o f several fluorochemicals. St. Paul (MN):3M Company. U.S. Environmental Protection Agency docket A R -226-1086. Gilliland FD, Mandel JS. 1996. Serum perfluorooctanoic acid and hepatic enzymes, lipoproteins, and cholesterol: a study o f occupationally exposed men. Am J Ind Med 29:560-568. Hansen KJ, Clemen LA, Ellefson ME, Johnson HO. 2001. Compound-specific, quantitative characterization of organic fluorochemicals in biological matrices. Environ Sei Technol 35:766-770. Olsen GW, Gilliland FD, Burlew MM, Burris JM, Mandel JS, Mandel JH. 1998. An epidemiologic investigation o f reproductive hormones in men with occupational exposure to perfluorooctanoic acid. J Occup Environ Med 40:614-621. Olsen GW, Burris JM, Mandel JH, Zobel LR. 1999. Serum perfluorooctane sulfonate and hepatic and lipid clinical chemistry tests in fluorochemical production employees. J Occup Environ Med 41:799-806. Olsen GW, Burris JM, Burlew MM, Mandel JH. 2000. Plasma cholecystokinin and hepatic enzymes, cholesterol and lipoproteins in ammonium perfluorooctanoate production workers. Drug Chem Toxicol 23:603-620. Olsen GW, Logan PW, Simpson CA, Burris JM, Burelw MM, Lundberg JK, Mandel JH. 2001a. Descriptive summary o f serum fluorochemical levels among employee participants o f the year 2000 Decatur fluorochemical medical surveillance program. St. Paul (MN):3M Company. U.S. Environmental Protection Agency docket AR-2261030a020a. Olsen GW, Schmickler MN, Tierens JM, Logan PW, Burris JM, Burlew MM, Lundberg JK, Mandel JH. 2001b. Descriptive summary of serum fluorochemical levels among employee participants o f the year 2000 Antwerp fluorochemical medical surveillance program. St. Paul (MN):3M Company. U.S. Environmental Protection Agency docket AR-226-1030a020b. Olsen GW, Burris JM, Burlew MM, Mandel JH. 2003a. Epidemiologic assessment o f worker serum perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) concentrations and medical surveillance examinations. J Occup Environ Med 45:260270. 000064 Page 9 Olsen GW, Butenhoff JL, Mandel JH. 2003b. Assessment of lipid, hepatic and thyroid function in relation to an occupational biologic limit value for perfluorooctanoate. St. Paul (MN):3M Company. U.S. Environmental Protection Agency docket AR-226. Olsen GW, Logan PW, Hansen KJ, Simpson CA, Burris JM, Burlew MM, Vorarath PP, Venkateswarlu P, Schumpert JC, Mandel JH. 2003c. An occupational exposure assessment o f a perfluorooctanesulfonyl fluoride production site. Biomonitoring. Am Ind Hyg Assoc J. (in press). Tandem Labs. 1999. Assay validation report. Quantitative determination o f PFOS, PFOSA, PFOSAA, N-MeFOSE-OH, N-EtFOSE, POAA, and PFHS in human serum by LC/MS/MS. Study No. NWBS98-082, Report No. NWBR99-005. NWT Inc., Salt Lake City, UT., U.S. Environmental Protection Agency docket AR-226-1208. Tandem Labs. 2001a. Quantitative determination of PFOS, PFOSA, PFOSAA, POAA, PFHS, M556 and M570 in human serum by LC/MS/MS. Assay revalidation report. Study No. NWBS00-040, Report No. NWBR00-108. NWT Inc., Salt Lake City, UT,, U.S. Environmental Protection Agency docket AR-226-1209. Tandem Labs. 2001b. Quantitative determination of PFOS, PFOSA, PFOSAA, POAA, PFHS, M556 and M570 in human serum by LC/MS/MS. Assay revalidation addendum report. Study No. NWBS00-040, Report No. NW BR00-122. NWT Inc., Salt Lake City, UT., US Environmental Protection Agency docket AR-226-1210. 3M Company. 2001. Documentation o f an Occupational Biological Limit Value (BLV) for Perfluorooctanoate [CF3(CF2)C02]. St. Paul (MN):3M Company. U.S. Environmental Protection Agency docket AR-226. 000065 35.0 n 30.0 25.0- ~ 20.0 aOEE. < O u. - 15.0- 10.0 A Figure 1. C ottag e G rove Flu o ro ch em ical M edical S u rveillan ce, PFO A C o ncentrations, N - 38 E m ployees, D ecem ber 2002 Page 10 00006C 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 EmDlovee Figure 2. Comparison o f PFOA Concentraions for Those Em ployees (n = 26) who had A Most Recent Previous Test Page 11 00006? Employee Figure 3. Cottage Grove Fluorochemical Medical Surveillance, PFOS Concentrations, N = 38 Employees, December 2002 3 .0 i 2.5 2.0 Page 12 0.5 0.0 12 34 56 iuiiiiiiiiiIIIIH 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 36 36 37 38 Employee g&oooo Figure 4. C om parison o f PFO S C oncen tratio n s fo r Those Em ployees w ho had M ost R ecent P revious Tests (N = 22) Page 13 000U&9 Employee