Document zQnOydB66eK0gye6qEZXYyjXg

NORTHERN KENTUCKY OFRCE SUITE 340 1717 DIXIE HIGHWAY COVINGTON, KENTUCKY 41011-4704 606-331-2638 513-361-2838 FAX: 513-381-6613 DAYTON, OHIO OFFICE SUITE 900 110 NORTH MAIN STREET DAYTON, OHIO 45402-1786 937-228-2638 FAX: 937-228-2816 R o b e r t A. B ilott (513)357-9638 bilott@taftlaw.com <c>03 ,, O 0 ( 2 , p.1 Vj-R s a s tG _ 'd & cJ~7 Ta.. T, STETTINIUS & HOLLISTER LL. 425 WALNUT STREET, SUITE 1800 CINCINNATI, OHIO 45202-3957 513-381 -2838 FAX: 513-381 -0205 www.taftlaw.com June 20, 2006 CLEVELAND, OHIO OFFICE 3500 BP TOWER 200 PUBLIC SQUARE CLEVELAND, OHIO 44114-2302 216-241-2838 FAX: 216-241-3707 COLUMBUS, OHIO OFFICE 21 e a s t s t a t e s t r e e t C o l u m b u s , Oh io 43215^221 614-221-2838 FAX:614-221-2007 O cr> CO rn ' 2 ---* ~ 'Z ) 1~T~ I TELECOPY AND FEDERAL EXPRESS Dr. Charles M. Auer USEPA 1201 Constitution Avenue, N.W. Room 3166A Washington, DC 20004 Jennifer Seed, Ph.D. USEPA 1201 Constitution Avenue, N.W. Room 6334A Washington, DC 20004 Gary Krueger Remediation Division Superfund & Emergency Response Section Minnesota Pollution Control Agency 520 Lafayette Road North St. Paul, MN 55155 Mary Dominiak USEPA 1201 Constitution Avenue, N.W. Room 441 OS Washington, DC 20004 Helen Goeden Minnesota Health Department 625 Robert St., N. St. Paul, MN 55164 Donald Kriens Industrial Division Land & Water Quality Section Minnesota Pollution Control Agency 520 Lafayette Road North St. Paul, MN 55155 r-o ro Nancy Seymour Environment Canada 351 St. Joseph Boulevard Gatineau, Quebec CANADA K1A0H3 Gloria Post New Jersey DEP 401 East State Street, 1st Floor P.O. Box 409 Trenton, NJ 08625 ro W0728220.1 V G P-2 June 20, 2006 Page 2 IRIS Hotline 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 o f 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 during a presentation at the American Occupational Health Conference in May o f 2006, entitled "Twenty-five year longitudinal study o f serum total cholesterol relating to a serum biomarker of exposure (serum perfluorooctanoate or PFOA) in a polymer production plant." RAB/mdm Enclosure Robert A. Bilott VV0728220.1 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 Sciences Address : 135 College Street, 3rd floor New Haven, CT 06510 Phone : 856-816-1539 Fax : 203-785-7391 Email : carine.sakrfa),vale.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. BACKGROUND Perfluorooctanoate (PFOA, C7F,5COO') 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 o f non occupationally 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 industrial hygiene surveillance program. The blood cholesterol levels and other covariates 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 from 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 cohort 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 serum PFOA for the entire cohort 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 least 2 measurements of serum PFOA (median: 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, and gender, there was a statistically significant positive association between serum PFOA and total cholesterol (Table 1). CONCLUSIONS Serum 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 further 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 Laboratory for Health and Environmental Sciences, Martin Slade MPH of the Yale Occupational and Environmental Medicine Program, and Ellen Eisen ScD o f the Harvard School of Public Health. Figure 1 Blood PFOA (ppm) versus calendar time P-5 Calendar tine Figure 2 Total cholesterol (mg/dl) versus age stratified by gender P-6 Age SEX " F Figure 3 Distribution of total cholesterol (mg/dl) p.8 Table 1 Longitudinal analysis of total cholesterol (mg/dl) by blood PFOA (ppm) and other covariates REFERENCES 1. bel FA, Sorenson SD, Roach DE. Health Status of plant workers exposed to fluorochemicals-a preliminary report. Am IndH yg 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: 614 622. 3. Olsen GW, Burris 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. Kaiman K, Corsolini S, Falandysz J, Fillmann G, Kumar KS, Loganathan BG et al. Perfluorooctanesulfonate and related fluorochemicals in human blood from several countries. Environ. Sei. 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 proliferatioa Exp Mol 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 Sei. 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 Sei. 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