Document a1n3wkQ6gOx3v6LzyZBxXZ0BN

^ C('~n~ _ ~003 ~ C~Ql~2 p. 1 +, ~ ~2 a~G _ 36 9 7 TA,. r, STETTINIUS & HOLLISTER LL . NORTHERN SUITE 340 1717 DIXIE HIGHWAY COVINGTON, KENTUCKY 41011 4704 KENTUCKY OFFICE CLEVELAND, OHIO OFFICE 3500 BP TOWER 425 WALNU, STUITSE T 180R0 EET 260 PUBLIC SQUARE CLEVELAND, OHIO 44114-2302 CINCINNATI, 606-331-2838 513-38126 3 8 FAX : 51 3-361-6613 f 216-241-2838 45202-3957 FAX : 218-241-3707 COLUMBUS, OHIO OFFICE DAYTON, OHIO OFFICE 513-381-2838 21 EAST STATE STREET SUITE 900 FAX : 513-381 -0205 COLUMBUS, OHIO 43215-422 1 110 NORTH MAIN STREET 614-221-2838 DAYTON, OHIO 454021786 937-228-2838 www.taftlaw .com FAX: 937-228-2816 FAX :614-221-2007 Q ROBERT A . BILOTT (513) bilott@taftlaw.com 357-9638 7-1 June 20, 2006 77 TELECOPY AND FEDERAL EXPRES S Dr . Charles M . Auer Mary Dominiak USEPA USEPA 1201 Constitution Avenue, N . W . 1201 Constitution Avenue, N . W . Room 3166A Room 4410S Washington, DC 20004 Washington, DC 20004 Jennifer Seed, Ph .D . Helen Goede n USEPA Minnesota Health Department 1201 Constitution Avenue, N .W . 625 Robert St ., N. Room 6334A St . Paul, MN 55164 Washington, DC 2000 4 Gary Krueger Donald Kriens Remediation Division Industrial Divisio n Superfund & Emergency Response Section Land & Water Quality Section Minnesota Pollution Control Agency Minnesota Pollution Control Agency 520 Lafayette Road North 520 Lafayette Road Nort h St . Paul, MN 55155 St . Paul, MN 55155 Nancy Seymour Gloria Post Environment Canada New Jersey DE P 351 St . Joseph Boulevard 401 East State Street, lst Floor Gatineau, Quebec P .O . Box 409 CANADA K 1 A OH3 Trenton, NJ 08625 W0728220.1 '~4~~ 9 ~'S~a p. 2 June 20, 2006 Page 2 IRIS Hotlin e EPA West Building EPA Docket Center, Room B-102 1301 Constitution Avenue, NW Washington, DC 20004 Re : PFOA Worker Exposure Health Effects Study Ladies and Gentlemen: In response to previous requests by the United States Environmental Protection Agency and other governmental entities for information relating to environmental and/or human exposures to PFOA, and in recognition of a potential threat to human health and/or the environment, we are enclosing at Exhibit A for inclusion in AR-226, OPPT-HQ-2003-0012, and the IRIS database for PFOA, a document recently made public duri ng a presentation at the American Occupational Health Conference in May of 2006, entitled "Twenty-five year longitudinal study of serum total cholesterol relating to a serum biomarker of exposure (serum perfluorooctanoate or PFOA) in a polymer production plant. " culy ytr ours, RAB/md m Enclosure Robert A . Bilott W0728220 . 1 p. 3 Name : Carine Sakr, MD MPH ~ Robin Leonard, PhD 2 Mark Cullen, MD 1 Program Affiliation :'-Yale Occupational and Environmental Medicine Program 2-Epidemiology Program at DuPont Haskell Laboratory for Health and Environmental Science s Address 135 College Street, 3d floor New Haven, CT 06510 Phone 856-816-1539 Fax :203-785-7391 Email : carine.sakr@,yale .edu TITLE Twenty-five year longitudinal study of serum total cholesterol related to a serum biomarker of exposure (serum perfluorooctanoate or PFOA) in a polymer production plant. BACKGROUN D Perfluorooctanoate (PFOA, C 7 F15COO-) is a perfluorinated carboxylate, primarily used as a surfactant in the production of fluoropolymer high-performance materials . Fluoropolymers are used in architectural fabrics ; chemical processing piping and vessels ; automotive fuel systems ; telecommunications and electronic wiring insulation ; and computer chip processing equipment and systems- in addition to consumer products such as cookware and apparel . PFOA has been found in the serum of production workers with occupational exposure ( 1 -3) . Lower levels of PFOA have been reported in serum samples of nonoccupationally exposed men and women in the USA as well as in other countries, which suggests a widespread, albeit low, exposure to the general population (4-8) . Animal studies suggested that the liver is the primary target organ for PFOA-induced toxicity in rats and monkeys . PFOA produced hypolipemia in rodents (9, 10) and increased liver weight as a result of mitochondrial proliferation in monkeys (11) . PFOA exposure also increased incidence of adenomas of the liver, pancreas, and testes in rats (12) . Previous studies in exposed workers evaluating the association between PFOA and total cholesterol have yielded conflicting results (13,14) . p. 4 METHODS The relationship between total cholesterol and serum PFOA was examined in a 25-year longitudinal study ( 1979-2004) with repeated measurements using a mixed effects model in a cohort of 454 workers with occupational exposure to PFOA . The serum PFOA levels used were part of an industri al hygiene surveillance program . The blood cholesterol levels and other covari ates were abstracted from the medical surveillance program at the plant . There were no available data on use of lipid lowering medications . Unless cholesterol was measured in the same year as PFOA, the cholesterol level corresponding to a PFOA test was interpolated fr om the values of the 2 nearest before and after dates . Univariate analyses were utilized to determine the distributions of PFOA and cholesterol . All analyses were conducted using a 95% level of confidence (alpha = 0 .05) in SAS version 9 .01 . RESULTS The coho rt included 334 males and 120 females . At the end of the study, 49.3% of the subjects were still employed ; the rest were either terminated (43 .4%) or dead (7 .3%). For those still employed, the mean age was 51 .3 years. The mean se rum PFOA for the entire coho rt was 1 .69 ppm (SD 3 .24) . Serum PFOA seemed to decrease with calendar time ( Figure 1) . All the people in the cohort had at le ast 2 measurements of serum PFOA ( medi an : 3 ; range 2-17) . Total cholesterol increased with age for both men and women (Figure 2) and had a close to normal distribution in the cohort ( Figure 3) . After adjusting for age, BMI, an d gender, there was a statistically signific an t positive association between se rum PFOA and total cholesterol ( Table 1) . CONCLUSION S Se rum PFOA is positively associated (p = 0 .007) with total cholesterol in a longitudinal analysis of exposed workers . The parameter estimate is 1 .152 mg/dl/ppm PFOA . However, this result is not adjusted for use of lipid lowering medications . The true relationship might be in fact stronger . Further studies should be considered to fu rther understand the relationship between exposure to PFOA and total cholesterol . ACKNOWLEDGMENTS The authors thank Kim Kreckmann and Craig Marshall of the Epidemiology Program at DuPont Haskell Laborato ry for Health and Environmental Sciences, Ma rtin Slade MPH of the Yale Occupational and Environmental Medicine Program, and Ellen Eisen ScD of the Harvard School of Public Health . p. 5 Figure l. Blood PFOA (ppm) versus calendar tim e PFOA (ppa) 30 PFOA (ppw) 30 28 28 26 26 24 22' 24 22 20 18, 16, 20 18 16 14 12' 14 12 10 8 4 2 4 2 to 8 6 01/01/75 0 01/01/80 01/01/85 01/01/90 01/01/95 01/01/00 01/ 0 1/06 Calendar time p. 6 Figure 2 Total cholesterol (mg/dl) versus age stratified by gender Total Chol .(mg/dl) 500 Total Chol .( mg/dl) 500 400 400 300 30 0 -0 . <. . .. _. .~~~f 200 ~ _,,~~~~,~ _ 200 100 100 0 0 10 20 30 40 50 60 Age SEX ""' F M 70 80 p. 7 Fieure 3 17 .5 Distribution of total cholesterol (mg/dl ) 15 .0 1x . s P 10 .0 t 7 .5 5 .0 2. 5 0- 82 .5 112 .5 142 .5 172 .5 202 .5 232 .5 262 .5 292 .5 322 .5 352 .5 382 .5 412 .5 442 .5 472 .5 Total Cholestarol (mg/dl) p. 8 Table 1 Longitudinal analysis of total cholesterol (mg/dl) by blood PFOA (ppm) and other covariates arame0i~,E~kir~ta~ '~ ~ ~~ : .1~, ,.~~ $laod PFOA 1 .1 52 ~~04 7 13)I~il 1 .14., Ag e Q:33" G~nier cmale) 71 :b9 ~r(fema ~ ~ f ~ 1 ;63 W .rr .~,y~-~' - , ~ '~54~_ukHx ."~ - p. 9 REFERENCE S 1 . Ubel FA, Sorenson SD, Roach DE . Health Status of plant workers exposed to fluorochemicals-a preliminary report . Am 1nd Hyg Assoc J. 1980 . 41 :584-589 . 2 . Olsen GW, Gilliland FD, BUrlew MM, Burris JM, Mandel JS, Mandel JH . An epidemiologic investigation of reproductive hormones in men with occupational exposure to perfluorooctanoic acid . J Occup Env Environ Med. 1998 . 40 : 614622 . 3 . Olsen GW, Bums JM, BUrlew MM, Mandel JH . Epidemiologic assessment of worker serum Perfluorooctanesulfonate (PFOS) and Perfluorooctanoate (PFOA) concentrations and Medical Surveillance Examination . J Occup Env Environ Med. 2003 . 45 :260-270 . 4 . Olsen GW, Church TR, Miller JP, Burris JM, Hansen KJ, Lundberg JK et al . Perfluooctanoate and other fluorochemicals in the serum of American red cross adult blood donors . Environ Health Perspect. 2003 . 111 :1892-1901 . 5 . Olsen GW, Huang HY, Helzlsouer KJ, Hansen KJ, Butenhoff JL, Mandel JH . Historical comparison of perfluorooctanesulfonate, perfluorooctanoate, and other fluorochemicals in human blood . Environ Health Perspect. 2005 . 113 :539-545 . 6 . Kubwabo C, Vais N, Benoit F . A pilot study on the determination of perfluorooctanesulfonate and other perfluorinated compounds in blood of Canadians . J. Environ . Monit. 2004 . 6 :540-545 . 7 . Kannan K, Corsolini S, Falandysz J, Fillmann G, Kumar KS, Loganathan BG et al . Perfluorooctanesulfonate and related fluorochemicals in human blood from several countries . Environ . Sci. Technol. 2004 . 38 :4489-4495 . 8 . Harada K, Saito N, Inoue K, Yoshinaga T, Watanabe T, Sasaki S et al. J Occup Health. 2004 .46 :141-147 . 9. Haughom B, Spydevold O . The mechanism underlying the hypolipemic effect of perflurooctanoic acid (PFOA), perfluorooctanesulphonic acid (PFOSA), and clofibric acid . Biochemica et Biophysica Acta. 1992 .1128 :65-72 . 10 . Pastoor TP, Lee KP, Perri MA, Gillies PJ . Biochemical and morphological studies of ammonium perfluorooctanoate-induced hepatomegaly and peroxisome proliferation . Exp Mo! Pathol. 1987 . 47 :98-109 . 11 . Butenhoff JL, Costa G, Elcombe C, et al . Toxicity of ammonium perfluorooctanoate (APFO) in cynomolgus monkeys after 26 weeks of oral dosing . Toxicol Sci. 2002 . 69 :244-257 . 12 . Biegel LB, Hurt ME, Frame SR, O'Connor JL, Cook JC . Mechanisms of extrahepatic tumor induction by peroxisome proliferators in male CD rats . Toxicol Sci . 2001 . 60:44-55 . 13 . Olsen GW, Burris JM, Burlew MM, MandelJH . Drug Chem Toxicol. 2000 . 23 :603-620 . 14 . Olsen GW, Burris JM, Burlew MM, Mandel JH . J Occup Env Environ Med. 2003 . 45 :260-270