Document MGMNMGQQbN1o1pb6krBjJ7ekz

OQT- 2 0 0 3 - O O I Z NORTHERN KENTUCKY OFFICE SUITE 340 1717 DIXIE HIGHWAY COVINGTON, KENTUCKY 41011 -4704 606-331-2838 $13-381-2838 FAX: $13-381-6613 DAYTON, OHIO OFFICE SUITE 900 110 NORTH MAIN STREET DAYTON, OHIO 45402-1786 937-228-2838 FAX: 937-228-2816 W T , STETTINIUS & HOLLISTER LL. 425 WALNUT STREET, SUITE 1800 CINCINNATI, OHIO 45202-3957 513-381-2838 FAX: 513-381-0205 www.taftlaw.com CLEVELAND, OHIO OFFICE 3500 BP TOWER 200 PUBLIC SQUARE CLEVELAND, OHIO 44114-2302 216-241-2838 FAX: 216-241-3707 COLUMBUS, OHIO OFFICE 21 EAST STATE STREET COLUMBUS, OHIO 43215-4221 814-221-2838 FAX:614-221 -2007 Roberta. Bilott (513) 357-9638 bilott@taf)law.com June 1, 2006 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 441OS 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 oCTN orno --a i - --) ~J --, T . X ro no c:r X] 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 W07t4386.l CONTAIN NO CB! m id P-2 June 1, 2006 Page 2 IRIS Hotline EPA West Building EPA Docket Center, Room B-102 1301 Constitution Avenue, NW Washington, DC 20004 Re: PFOA Human 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 copy of a human health study relating to PFOA that does not appear to have been previously produced. We represent the Plaintiffs in a lawsuit currently pending against the 3M Company in Minnesota State Court relating to the contamination of private and public drinking water supplies with PFOA, PFOS, and other perfluorochemicals attributable to 3M's operations and activities. Among the documents recently produced by 3M in that case was a copy of the enclosed draft article and memo, both originally marked confidential by 3M. Upon review of that article, we noticed that the authors' conclusion that "PFOA is associated with alterations in peripheral blood lymphocyte numbers in PFOA production workers, suggesting that cell-mediated immunity may be affected by PFOA" appeared inconsistent with 3M's public representations that there is no evidence of any human health effects associated with PFOA exposure among its workers.- The article and its conclusions also i' For example, 3M is currently claiming on its corporate website that: The extensive research to date shows no adverse human health effects resulting from exposure to PFOS or PFOA. This is supported by observational research involving thousands of 3M production employees. That research was conducted by 3M and by the University of Minnesota under grants from 3M. In all of our years of research we have not found any evidence of adverse health effects in our employees. Over 25 years of medical surveillance of exposed employees failed to identify any health W0714386.I P-3 June 1, 2006 Page 3 did not appear to be contained or referenced within any of documents produced to date by 3M in response to USEPA's requests for all available human health data relating to PFOA exposures. {See AR-226) Although it appeared that the enclosed article had been prepared for publication, we could not find any reference to the article or its conclusions in any of the published literature on PFOA after it apparently had been submitted to 3M for pre-publication review in 1993. Because the enclosed article reveals important human health data that did not appear to have been included or referenced in any of the on-going reviews or discussions of human health effects related to PFOA (including proceedings before the USEPA Science Advisory Board PFOA Review Panel) or in any of the submissions 3M had made to the public dockets relating to PFOA, we asked 3M in a letter dated May 1, 2006, to withdraw its claim of confidentiality over the enclosed materials- and to confirm whether the study and its conclusions had previously been disclosed by 3M or any other entity. On May 23, 2006, we received the enclosed letter (Exhibit B) from 3M's counsel withdrawing 3M's claim of confidentiality over the enclosed documents. With respect to any prior disclosure of the enclosed study and its conclusions, 3M confirmed that a decision was made not to publish the enclosed article after it had been submitted to 3M for review. 3M claims, however, that "information" contained within the article had previously been disclosed when 3M submitted a copy of Dr. Frank Gilliland's 1992 Ph.D. dissertation to USEPA on May 26, 2000, and that other "data addressed by his [Dr. Gilliland's] dissertation" was provided to USEPA when 3M submitted a copy of a 1993 publication by Dr. Gilliland to USEPA on January 28, 2000. effects attributable to exposure to PFOA or PFOS.... These studies and medical surveillance results have been published in peerreviewed scientific journals and shared with the EPA and with regulatory agencies in other countries. (Exhibit D) - Because 3M marked the documents "confidential" under the Minnesota Court's protective order, we were prohibited under the terms of that order from sharing or disclosing the documents with any regulatory entities without first either obtaining 3M's permission or obtaining 3M's agreement to withdraw its confidentiality claim. W07I4386.1 P-4 June 1, 2006 Page 4 The copy of Dr. Gilliland's 1992 dissertation submitted to USEPA in 2000^ does refer to some of the data upon which the enclosed article is based. But the dissertation abstract summarizing that data states that a "positive association between hemoglobin, mean cellular volume, and leucocyte counts with PFOA," was found, suggesting the opposite of the conclusion provided in the enclosed article that PFOA exposure is negatively associated with peripheral blood lymphocyte counts. In addition to clarifying and explaining the specific inverse association between PFOA exposure and peripheral blood lymphocyte counts, the enclosed article also appears to include additional, clarifying data that does not appear to have been included in the earlier 1992 dissertation. (See, e.g., Exhibit A, at Table 4). Moreover, when 3M submitted the 1992 dissertation to USEPA in 2000, the abstract it attached to the document to summarize the key findings of the dissertation includes no reference to any immune system effects that are the subject and focus of the attached, clarifying article. (See AR-226-0473). Thus, those relying upon 3M's summary of the key findings in the 1992 dissertation or the abstract would not necessarily have been alerted to the association between PFOA exposure and peripheral blood lymphocyte numbers in PFOA production workers that is clarified and highlighted in the enclosed article*'. In addition, the 1993 publication referred to by 3M as addressing "data covered" in the 1992 dissertation addresses only the mortality study findings addressed in the dissertation and does not appear to reference the immune system findings. See Gilliland, et al., Mortality Among Employees o f a Perfluorooctanoic Acid Production Plant, J. Occup. Med. 1993, 35.950-954 (finding that "ten years of employment in exposed jobs was associated with a 3.3-fold increase (95% CI, 1.02 to 10.6) in prostate cancer mortality compared to no employment in PFOA production" among 3M's employees). Although a second article also was published addressing "data covered" in Dr. Gilliland's 1992 dissertation, that article similarly appears to make no mention of the lymphocyte data at issue in the enclosed article. See Gilliland & Mandel, Serum Perfluorooctanoic Acid and Hepatic Enzymes, Lipoproteins, and Cholesterol: A Study o f Occupationally Exposed Men, 29 Am. J. Indus. Med. 560-568 (1996). l> The copy of the 1992 dissertation available in AR-226 appears to be missing the following pages: 72, 126-127,134, 175, 198-199, 235, and 280-283. 3M has since produced to us an additional copy of the dissertation with copies of the missing pages. Those pages are attached at Exhibit C. - In that regard, we note that the lymphocyte findings addressed specifically in the enclosed article do not appear to be mentioned in USEPA's draft hazard or risk assessments for PFOA, although the 1992 dissertation is listed among the references. W07I4386.I P-5 June 1, 2006 Page 5 Because the enclosed study appears to reveal an association between PFOA exposure and alteration of the human immune system that does not appear to have been considered in the reviews conducted to date of human health effects related to PFOA, we are providing the enclosed study so that this additional data can be considered and evaluated in connection with ongoing regulatory investigations related to PFOA. RAB/mdm Enclosures W0714386.1 June 1,2006 Page 6 bcc: J. Mark Englehart, Esq. (w/o ends.) Gale D. Pearson, Esq. (w/o ends.) R. Edison Hill, Esq. (w/o ends.) Larry A. Winter, Esq. (w/o ends.) Gerald J. Rapien, Esq. (w/o ends.) W0714386.1 P-7 Internal Correspondence TO: Fluorochemical Steering Committee Members FROM: Jeff Mandel, M .D ., 333-8670 (220-3W -05) SUBJECT: Papers/Dr. Gilliland DATEL: Decem ber 7,1 9 9 3 These are two additional papers that are being prepared by Dr. Gilliland. They need our input/approval before being submitted for publication. The papers are negative for the most part. W e're working with him regarding some of the wording. W e're operating under the premise that these sorts of topics need 3M support. Please send your comments back to m e by the end of the month so I can communicate with Dr. Gilliland. JH M /vlk 3MA00323875 p.8 Peripheral Blood Lymphocyte Count in Men Occupationally Exposed to Perfluorooctanoic Acid Frank D. Gilliland, M.D., Ph.D. Jack S. Mandel Ph.D. Affiliations: Division of Environmental and Occupational Health, School of Public Health, University of Minnesota, Minneapolis (F.D.G); and Department of Internal Medicine, Occupational and Environmental Medicine Section, St.Paul Ramsey Medical Center, St.Paul, Minnesota (F.D.G.) Reprint requests should be addressed to Frank D. Gilliland, University of New Mexico School of Medicine, New Mexico Tumor Registry, 900 Camino de Salud NE, Albuquerque, NM 87131. Telephone (505) 277-5541, Fax (505) 277-7041. This study was supported in part by NIOSH Grant T150h07098-16 and 3M Medical Department Running title: Lymphocyte count and PFOA 3MA00323876 ABSTRACT Studies in Rhesus monkeys suggest that perfiuorooctanoic acid (PPOA) has immunotoxic effects on the cell-mediated immune system in primates. The predominant histopathological lesion in PFOA-treated monkeys was diffuse atrophy of lymph nodes and splenic germinal centers. Although PFOA accounts for the majority of fluorine present in the serum of the general population and in occupationally exposed workers, little information is available concerning human responses to PFOA exposure. To assess whether PFOA exposure is associated with effects on the human cell-mediated immune system, we examined the cross-sectional associations between peripheral blood lymphocyte counts and PFOA in 115 workers employed at a PFOA production plant. Total serum fluorine was used as a surrogate measure for serum PFOA levels. Peripheral blood lymphocyte count was significantly associated with total serum fluoride level; however, the magnitude and direction of the relationship was dependent on smoking, alcohol use, and obesity status. For example, for non-smokers and moderate drinkers, an increase of 10 ppm in total serum fluoride was associated with a decrease in lymphocyte count of 1640 cells in non-obese (BMI=25 kg/m^) workers and by 925 cell in obese workers (BMI=35 kg/m^). PFOA is associated with alterations in peripheral blood lymphocyte numbers in PFOA production workers, suggesting th a t cell-mediated immunity may be affected by PFOA. KEY WORDS perfiuorooctanoic acid, epidemiology, immune toxicity, lymphocyte count p. 10 INTRODUCTION Perfluorooctanoic acid (PFOA) is widely used in industrial processes and consumer products as a result of its unique chemical properties and potent surface activity (Griffith, 1980). Because PFOA has a long biological half-life, small frequent doses can accumulate to appreciable levels (Ubel, 1980). As a result, PFOA has been found in the serum of all human population studied, and accounts for the majority of fluorine present in the serum of populations in industrialized countries1". Little is known about the toxic potential of PFOA in humans; however, studies have suggested that the cell-mediated immune system may be a site of toxicity in primates. Rhesus monkeys treated with oral PFOA developed histologic changes in spleen and lymph nodes. The primary histopathologic lesion was atrophy in lymph node and splenic germinal centers1. The immune system of rodent species has not been reported to undergo similar histopathologic changes in subacute and chronic feeding studies 1. No data are available concerning immunotoxicity in humans. Because PFOA is present in the serum of exposed workers and in the general population 3'7, it is a matter of concern whether the findings in monkeys indicate the potential for human immunotoxicity. To assess whether PFOA could affect the cell-mediated immune system in humans, we studied the association of PFOA, as measured by total serum fluorine, with peripheral blood lymphocyte count (PBL) in 115 occupationally exposed employees at a plant that produces PFOA. MATERIALS AND METHODS 3MA00323878 All current workers employed in PFOA production over the 5 previous years and a sample of workers in jobs with no apparent PFOA exposure for the previous 5 years were invited to participate. Participants had vital parameters measured in the plant medical department by an occupational health nurse, completed a medical history questionnaire, and underwent venipuncture. Blood was drawn for assays of peripheral lymphocyte count. A fluorine-free 15 ml vacutainer was used to collect blood for total serum fluorine determination. Total serum fluorine was used as the measure of PFOA in this occupational group. Total serum fluorine was determined using the sodium biphenyl extraction and atomic absorption spectrometry 8. Pearson correlation coefficients were calculated to assess the univariate associations between PBL and age, body mass index (BMI), cigarette use, and alcohol use. Linear multivariate regression models were fit to estimate the associations of PBL count with PFOA, adjusted for age, BMI, cigarette use, and alcohol use. Two way interactions between total serum fluorine and the four covariates were evaluated using residual analysis, model fit, and tests of significance. Interaction terms were included in the final model if biologically plausible and if the parameter estimate for the interaction term was significant at the alpha =.10 level. RESULTS Participant characteristics are displayed in Table 1. Total serum fluorine values ranged from 0 and 26 ppm with a mean of 3.3 ppm. Twenty-three (20.0%) participants had serum values less than 1 ppm, 6 (5.2%) had values between 10 and 15 ppm, and 5 (4.4%) had values greater than 15 ppm. Table 2 presents the correlation coefficients between PBL and total serum fluorine, age, BMI, alcohol use, and cigarette consumption. Peripheral blood lymphocyte count was significantly correlated with total serum fluorine (r=. 19, p=.04). The final regression model for PBL, which adjusted for age, BMI, cigarette use, and alcohol use, included data for 111 workers; 4 of the 115 workers had missing assay values and were excluded from the analysis (Table 3). Total serum fluorine was inversely associated with PBL; however, the relationship was complex, with significant interactions between total serum fluorine and BMI, cigarette vise, and alcohol use. Table 4 illustrates the relationship for a 10 ppm change in toted serum fluorine for combinations of smoking, alcohol consumption, and BMI status. In moderate drinkers (13oz alcohol per day), PBL decreased in the categories of smoking and of obesity; in light drinkers (<loz per day), PBL decreased in non-obese smokers only. D iscussion Serum PFOA level is associated with changes in the cell-mediate immune system, as evidenced by changes in PBL; however, the relationship depends upon smoking, alcohol use, and obesity. PFOA could modulate cell counts by altering the known effects of smoking, alcohol consumption, and adiposity on peripheral leukocyte counts (refs). No human studies of the effect of PFOA on the immune system are available for comparison; however, a study of this group of workers suggests that PFOA may modify the hepatic response to p. 13 alcohol and obesity. Modulation of endobiotic and xenobiotic metabolism could represent a common mechanism for the observed association of PFOA with alterations in hepatic and immune response. The relationship between the changes in PBL in humans and the lymph node and splenic germinal center atrophy observed in monkeys is not clear. Changes in PBL may be unrelated to germinal center atrophy. Alternatively, small changes in PBL could reflect larger changes in T cell subsets. In addition, the modification of the relationship between smoking and PBL by PFOA could be the result of changes in the number of particular T cell subsets. Furthermore, PFOA may be associated with changes in immune function beyond simple changes in cell number. Cytokine signaling is important in immune function and could be altered by PFOA exposure 27. The response to antigen binding depends upon rearrangement of membrane proteins. Changes in the membrane physical characteristics produced by the potent surfactant action of PFOA could alter immune responses. Interpretation of the findings requires careful consideration of the study limitations. Given the occupational study setting, the voluntary participation, and the requirements for blood sample collection, the overall participation was unexpectedly high, and non-response bias is likely to be small. Workers not included may have had a different response pattern than those who were included. Migration out of the high exposure jobs is unlikely to be the result of subclinical changes in PBL counts. The vast majority of workers who had significant exposure over the previous 5 years would be included in the study sample as the turn-over rate in plant employees was low (3% per year) and the study included all current employees with appropriate 3MA00323881 p. 14 job histories. Selection bias is not a likely explanation for the findings in this study. Total serum fluorine was used as a surrogate variable for PFOA exposure. The use of total serum fluorine has been validated in past biological monitoring in the plant and other plants using PFOA 2. Approximately 90% of total serum fluorine in workers was reported to be in the form of PFOA 2-8. Total serum fluorine is likely to be highly correlated with serum PFOA in this cohort. The coefficient of variation for total serum fluorine was 66%. At the low end of the spectrum (< 1 ppm), where the assay is limited by sensitivity, the total serum fluorine values may overestimate the true value. The measurement errors are likely to lead to an underestimate of the effect of PFOA on the physiologic endpoints. The duration of exposure may be an im portant determinant of PFOA level and effect; however, information on the duration of employment in exposed jobs was not available, because plant records did not contain sufficient information to reconstruct exposures. Inflammatory and infectious processes, which are major determinants of PBL, were not assessed in this study. Because there is no evidence that these processes are related to total serum fluorine or serum PFOA, they are unlikely to confound the estimated relationships. The changes in PBL counts associated with PFOA exposure present a complex picture. Alcohol use, cigarette use, and BMI modified the association of cell count with PFOA. The magnitude of these associations is not clinically significant from an infectious disease perspective; however, judgment as to the clinical relevance of such changes must await further study. More 3MA00323882 research is needed in the area of PFOA immunotoxicity. The findings of the present study need to be confirmed. Changes in T cell subsets could be confirmed by immunophenotyping lymphocytes using well established flow cytometry methods 28-29. In addition, the standard immunotoxicologic assessment defined by the National Toxicology Program 30 needs to be conducted for PFOA. 3MA00323883 Table I Participants characteristics total fluorine (ppm) age (years) BMI (kg/m2) Alcohol use <1 ounce per day 1-3 onces per day >3 onces per day non-response mam 3.3 39.2 26.9 range 0-26 24-59 18.8-40.5 number percent 87 75.6 20 17.4 0 0.0 8 7.0 Cigarettes use non-smoker current smoker non-response 85 73.9 28 24.4 2 1.7 3MA00323884 TABLE2 Pearson correlation coefficients between total serum fluoride, age, body mass index (BMI), daily alcohol use, daily tobacco consumption, and peripheral blood lymphocyte count Total fluorine (ppm) LYMPHOCYTES .19 p=.04 Age (years) -.05 BMI Alcohol Tobacco (kg/m2) (oz/day) (cigs/day) .04 .15 .28 p=.002 3MA00323885 TABLE 3 Linear multivariate regression model of factors predicting the lymphocyte count among 111 workers. Variable P Intercept 2205.6 Total Fluorine (ppm) ,, -342.7 Alcohol * SE(P) 611.1 125.3 Pvalue .0005 .007 low (<loz/day) nonresponse (NR) low X Fluorine NB X Fluorine Cigarettes/day -526.6 -977.1 189.0 247.9 34.0 222.7 355.7 52.3 103.9 6.9 .02 .007 .0005 .02 .0001 Cigs/day X Fluorine** -3.3 1.45 .02 BMI (kg/m2) 1.58 19.6 .94 BMI X Fluorine** 7.15 4.1 .08 R2= .35 #Reference category is drinkers who consumed 1-3 oz ethanol/day. *interaction terms alcohol category by total fluoride; dgarettes/day by total fluoride, BMI by total fluoride. 3MA00323886 Table 4 Change in lymphocyte count for 10 ppm increase in total serum fluorine < 1 oz. alco h o l/d ay Non-smoker BMI 25 mg/Kg2 +750 BMI35mg/Kg2 +965 Smoker (20 cigs/day) -406 +306 1-3 oz. o f a lc o h o l/d a y Non-smoker BMI 25 mg/Kg2 -1640 BMI 35 mg/Kg2 -924 Smoker (20 cigs/day) -2300 -1585 3MA00323887 p. 20 References 1. Griffith F, Long J. Animal Toxicity Studies with Ammonium perfluorooctanoate. Am Ind Hyg Assoc I980;41: 57G-583. 2. bel F, Soreson S, Roach D. Health Status of Plant workers exposed to fluorochemicals: a Preliminary Report Am Ind Hyg Assoc 1980;41: 584-589. 3. Taves D. Evidence that there are two forms of fluoride in human serum. Nature 1968:217: 1050-51. 4. Taves D. Comparision of "organic" fluoride in human and nonhuman serums. J Dent Res 1971:50: 783. 5. Taves D, Guy W, Brey W. Organic Fluocarbons in Human Plasma: Prevalence and Characterization. In: Filler R, ed. Biochemistry Involving Carbon-Fluorine Bonds. Washington, DC: American Chemical Society.l976:117-134. 6. Guy W. Fluorocompounds of Human Plasma: Analysis, Prevalence, purification, and Characterization, Ph.D. thesis. Rochester, NY: University of Rochester, 1972. 7. Guy W, Taves D, Brey W. Organic fluorocompounds in human plasma: prevalence and characterization. In: Filler R, ed. Biochemistry involving carbon-fluorine bonds. ACS Symposium Series. New York: American Chemical Sodety.l976:117-134. 8. Venkateswarlu P. Sodium biphenyl method for determination of covalently bound fluorine in organic compounds and biological materials. Anal Chem 1982;54: 1132-1137. 9. The 3M company R. Two Year Oral Toxidty/Carcinogenicity Study of FC-143. 1986, Riker Laboratories: 10. Kennedy B, Gilbertson A. Increased erythropoiesis induced by androgenic hormone therapy. NEJM 1957:256: 719. 11. Steinglass P, Gordon A, Charipper H. Effect of castration and sex hormones on the blood of rats. Proc Soc Exp Biol Med 1941;48: 169. 12. Rishpon-Meyerstein N, Kilbridge T, Simone J, Fried W. The effect of testosterone on erythopoietin levels in anemic patients. Blood 1968;31: 453-460. 13. Alexanian R. Erythropoietin and erythopoiesis in anemic men following androgens. Blood 1969:33: 564. 14. Shahidi N. Androgens and erythropoiesis. NEJM 1973:289: 72. 15. Palacios A, Campfield L, McClure R, Steiner B, Swerdloff R. Effect of testosterone enanthate on hematopoeisis in normal men. Fertility and Sterility 1983;40: 100-104. 16. Cunningham G, Silverman V, Thomby J, Kohler P. The potential for an androgen male contraceptive. J Clin Endocrinol Metab 1979;49: 520. 17. Mauss J. Borsch G, Bormacher K, Richter E, Leyendeck G, Nocke W. Effect of long term testosterone enanthate on male reproductive function. Acta Endocrinol (Copenh) 1975:78: 373-384. 3MA00323888 18. Tell G, Grimm Jr. R. Vellar O, Theodorsen L. The relationship of white cell count, platelet count, and hematocrit to cigarette smoking in Adolescents:the Oslo Youth Study. Circulation 1985;72: 971-974. 19. Hansen L. Grimm Jr. R, Neaton J. The relationship of white blood cell count and othe cardiovascualr risk factors. Int J of Epidem 1990;19: 881-888. 20. de Labry L, Campion E, Glynn R, Vokonas P. White blood cell count as a predictor of mortality: Results over 18 years from the normative aging study. J Clin Epidemiol 1990;43: 153-157. 21. Grimm Jr. R, Neaton J, Lugwig W. Prognostic Importance of the white blood count for coronary, cancer, and all-cause mortality. JAMA 1985;254: 1932-1937. 22. Zalokar J, RichardJ, Claude J. Leukocyte count, smoking and Myocardial infarction. NEJM 1981:304: 465-468. 23. Friedman G, Klatsky A, Siegelaub A. The leukocyte count as a predictor of myocardialinfarction. NEJM 1974;290: 1275-1278. 24. Friedman G, Fireman B. the leukocyte count and cancer mortality. Am J Epidemiol 1991:133: 376-380. 25. Kannel W, Anderson K, Wilson P. White blood cell count and cardiovascular disease. Insights from the Framingham Study. JAMA 1992;267: 1253-1256. 26. Manttari M, Manninen V, Koshinen P, et al. Leukocytes as a coronary risk factor n a dyslipidemic male population. Am Jeart J 1992;123: 873-7. 27. Youssef J, Iqwe O. Cunningham M. Regulation of hepatic inositol trisphosphate receptors by peroxisome proliferators. The Toxicologist 1992;12: 37. 28. Robinson J, Pfeifer R. New Technologies for use in Toxicology Studies: Monitoring the effects of xenobiotics on immune function. J Am Col Toxicol 1990;9: 303-317. 29. Tollerud D. Clark J, Brown L, et al. The effect of cigarette smoking on T cell subsets. Am J Respir Dis 1989;139: 1446-1451. 30. Dean J, Comacoff J, Rosenthal G, Luster M. Immune system: Evaluation of injury. In: Hayes A, ed. Principles and Methods of Toxicology. New York: Raven Press.l989:741-760. 31. Davis J, Davis R. Acute effects of tobacco cigarette smoking onthe platelet aggregation ratio. Am J Med Sci 1978:278: 139-143. 32. Fuster V, Chesebro J, Frye R, Elveback L. Platelet survival and the development of coronary artery disese in the young adult: Effects of cigarette amoking, strong family history, and medical threapy. Circulation 1981;63: 546-551. 33. Belch J. McArdle B, Burns P. The effects of acute smoking on platlet behavior, fibrinolysis, and hematology in habitual smokers. Thromb Haemostas 1984;51: 6-8. 34. Murchison L, Fyfe T, Lowe G, Forbes C. Effects of cigarette smoking on serum-lipids, blood glucose, and platelet adhesiveness. Lancet 1966:i: 182-184. p. 22 35. FitzGerald G, Oates J, Nowak J. Cigarette smoking and hemostatic function. Am Heart J 1988,115: 267-271. 36. Renaud S, Blanche D, Dumont D, Thevenon C, Wissendanger T. Platelet function after cigarette smoking in relation to nicotine and carbon monoxide. Clin Pharmacol Ther 1984:36: 389-395. 37. Green M, Peled I, Najenaon T. Gender differences in platelet count and its association with cigarette smoking in a large cohort in Israel. J Clin Epidemiol 1992;45: 77-84. 38. Packman M, Mustard J. The role of platelets in the development and complications of atherosclerosis. Semin Hematol 1986;23: 8-26. 39. Mehta J, Mehta P. Role of blood platelets in coronary artery disease. Am J Cardiol 1981;48: 366-373. 40. Cook J, Murray S, Frame S, H urtt M. Induction of Leydig cell adenomas by ammonium perfluorooctanate: A possible endocrine related mechanism. Tox Appl Pharm 1991,113: 209 213. 41. Roberts S, Nett T, Hartman H, Adams T, Stoll R. SDZ 200-110 induces Leydig cell tumors by increasing gonadotopins in rats. J Am Coll Toxicol 1990;8: 487-505. 3MA00323890 MASLON May 22, 2006 p 612.672.8200 f 612.672.8397 www.masion.com 3 300 Wells Farco C enter 90 S outh S eventh S treet M inneapolis, M innesota 55402-4140 Michael C. McCarthy Direct Phone: (612) 672-8347 Direct Fax: (612)642-8347 mike.mccarthy@maslon.com Robert A. Bilott Taft, Stettinius & Hollister, LLP 425 Walnut Street, Suite 1800 Cincinnati, OH 45202-3957 Via Federal Express Re: Palmer, et al. v. 3M Company, Court File No. C2-04-6309 Dear Mr. Bilott: This letter responds to your multiple inquiries regarding document 3MA00323875-890, which is an undated draft manuscript by Gilliland & Mandel produced to Plaintiffs from 3M's files. Counsel for 3M has now spoken with Dr. Frank Gilliland, who is the author of the document, as well as Dr. Jack Mandel, who is listed as a co-author. Because the document is Dr. Gilliland s intellectual property, 3M felt it was important to obtain Dr. Gilliland's permission before providing you with a non-confidential copy. I am enclosing a copy of the document bearing the Bates numbers but without the Palmer protective order legend. Dr. Gilliland tells us that the document in question is an "early draft" of a potential manuscript, which he decided not to pursue. The decision not to pursue publication of the manuscript was his alone. It was 3M's understanding, based on a June 29,1993, letter from Dr. Gilliland (3MA10017137), that he intended to submit three papers based on his student dissertation for publication. Two papers were published. Dr. Gilliland has informed us that he concluded that there was no finding that warranted publication of a third manuscript. You asked whether the information in the document has been disclosed previously. The answer is yes. The document was based on Dr. Gilliland's Ph.D. dissertation, which was completed in 1992 and has been available through the University of Minnesota medical school library since 1993.' In addition, Dr. Gilliland authored a 1993 publication that addressed data The dissertation was cataloged by the University of Minnesota on March 10, 1993. See the catalog entry at http://satum.oit.umn.edU/F/Y23UTYA6V2J 1Q64F4FIPT7SK4B358FVAF4HHX2CFP1X62LR2- B829104?func=full-set-set&set_number=019979&set_entry=000026&format=999. The catalog entry notes that the dissertation is available for normal library loan: Availability TC Bio-Medical Library QC463.F55 G481f 1992 Regular Loan. In addition, as you or your experts are no doubt aware, dissertations are customarily lodged not only with the university library, but also with a dissertation service established by the University of Michigan known as University Microfilms, www.umi.com, and now operated by Proquest at www.proquest.com. Through this service, dissertations are widely available through any library or over the internet. Researchers often start by searching this database to see if others Robert A. Bilott May 22, 2006 Page 2 MASLON covered by his dissertation. See Gilliland, et al., Mortality Among Employees of a Perfluorooctanoic Acid Production Plant, J Occup Med 1993; 35:950-954. 3M submitted this publication along with several related publications on fluorochemical production worker medical surveillance to U.S. EPA on January 28,2000, and also submitted Dr. Gilliland's dissertation to U.S. EPA on May 26, 2000. Both of these submissions are available in EPA's public dockets (the 8(e) docket and the AR-226 docket respectively). In response to your letter of this morning, asking for a copy of the dissertation, I am also enclosing a copy of that document, which has been produced to you at 3MA00749385-681, without a confidentiality legend. In short, because the data discussed in the document have been public and widely available since at least 1993, Dr. Gilliland graciously consented to the release of the document without a confidentiality legend. M C M :m lt cc: Dr. Frank Gilliland (w/enc. - via U.S. Mail) Dr. Jack Mandel (w/enc. - via U.S. Mail) Plaintiffs' counsel (w/o enc. - via U.S. Mail) Defendant's counsel (w/o enc. - via e-mail) Michael C. McCarthy have already addressed a topic. Dr. Gilliland's dissertation has been available through this service, and can be located and ordered directly over the internet or through libraries world-over. p. 25 TABLE 4.1 J9 TOTAL SERUM FLUORIDE DISTRIBUTION 3M CHEM OUTE PLANT, COTTAGE GROVE. MINNESOTA TOTAL FLUORINE (PPM) <1 1-3 >3-10 >10-13 >15-23 TOTAL MEANTF SO MEDIANTF RANGE NUMBER 23 65 16 6 5 115 3.3 4.7 2 0-26 PERCENT 20.0 5&5 13J 5.2 4.4 100J> 72 3M A00346022 p. 26 TABLE 4.1.64 LINEAR MULTIVARIATE REGRESSION MODEL OF FACTORS PREDICTING THE TRIGLYCERIDES AMONG 111 MALE WORKERS. 3M CHEMOUTE PLANT, COTTAGE GROVE. MINNESOTA Variable B sm p-value Intercept -114.50 117.20 .33 Total Fluoride (ppm ) 2.38 2.31 .15 Cigarettes/day 2.28 1.05 .03 BMI (kg/m2) 6.07 3.39 .08 Age (years) 2.32 1.44 .11 Alcohol # low (<1oz/day) nonresponse (NR) Free Testosterone* -11.48 -19.94 7.34 29.4 49.03 3.37 .70 .69 .03 Bound Testosterone* -.21 .08 R^* .19 Reference category is moderatedrinkerswhoconsume 1-3 oz ethanol/day. "ng/tfl .009 126 3M A00749524 p. 27 TABLE 4 1.65 PEARSON CORRELATION COEFFICIENTS BETWEEN TOTAL SERUM FLUORIOE. AGE. BODY MASS INDEX (BMI), DAILY ALCOHOL U S E DAILY TOBACCO CONSUMPTION. AND HEPATIC PARAMETERS 3M CHEMOLITE PLANT. COTTAGE G R O VE MINNESOTA TOTAL FLUORINE (ppm) AGE (years) BMI (IC0AR2) ALCOHOL TOBACCO (oz/day) (dgs/day) sGor .01 -.10 .09 .12 -.11 SGPT~ GGT* .01 .01 20 P -.02 -.04 .12 27 P -.0 0 4 AKPH** -.03 .2 7 .19 P -.0 0 4 P -.0 4 SERUM GLUTAMIC OXALOACETIC TRANSAMINASE RJ/dl "SERUM GLUTAMIC PYRUVIC TRANSAMINASE lU/dl GAMMA GLUTAMYL TRANSFERASE lU/dl ALKALINE PHOSPHATASE lUAH .03 .15 -.1 9 ' c>-.05 -.11 .03 .26 D -.006 127 3M A00749525 TABLE 4.1.72 ALKALINE PHOSPHATASE (AKPH) BY BODY MASS INDEX. A G E SMOKING AND DRINKING STATUS 3M CHEMOLITE PLANT. COTTAGE GROVE. MINNESOTA N (% ) AKPH (lU/dl) MEAN SD MEDIAN RANGE TEST BMI <25 41(35.7) 79 22.1 75 38-153 F-1A3 25-30 57(49.6) 84 21.9 81 41-153 P-22 >30 17(14A) 90 27.1 90 43-153 AGE <30 21(18.3) 78 22-2 76 38-153 F-2.78 31-40 48(41.7) 80 20.3 76 50-15. P-.4S 41-50 27(23.5) 86 24.1 83 43-153 51-60 19(16.5) 95 24.1 94 41-130 Alcohol <loz/d 87(813) 85 24JD 2 38-153 F-2J55 i-Soz/tf 20(18.7) 77 16.9 75 51-124 P-.16 missing 8 82 22.5 70 60-115 Tobacco smokar 28(24A) 85 23.8 85 61-153 F-6.48 nonsmokar 85(752) 77 22.0 77 38-153 P-.012 missing 2 86 24.8 86 68-103 TOTAL 115 univariate Anova 134 3M A 00749532 TABLE 4.2.20 NUMBERS OF DEATHS AND STANDARDIZED MORTALITY RATIOS (SMRs) BY LATENCY. BASED ON MINNESOTA W HITE MALE RATES, AMONG MALE EMPLOYEES EVER EMPLOYED IN THE CHEMICAL DIVISION, 1947-1989. Cause of Death LATENCY 1 5 YEARS " B5------ Exp SKiR 95% Cl All causes Cancer Gastrointestinal Colon Pancreas Respiratory Lung Prostate Lymphopoietic Cardiovascular All Gastrointestinal AH respiratory Diabetes Injuries 105 34 9 7 4 10 9 3 4 44 4 5 2 6 128.4 29.95 8.30 3.00 1.75 9.98 9.50 1.87 3.28 64.67 6.37 6.49 1.72 8.54 .82 1.14 1.08 1.33 2.28 1.00 .95 1.61 1.72 .68 .63 .77 1.17 .70 -67-.99 .79-1.59 .49-2.06 .36-3.42 .61-5.85 .48-1.94 .43-1.80 .32-4.70 .33-3.12 .49-.91 .17-1.61 .25-1.80 .43-4.21 .26-1.53 Abbreviations used are: Obs, observed; Exp. expected; Cl. confidence interval; CHD, coronary and atherosclerotic heart disease; CD, Chemical Division. 175 3M A00346125 p. 30 5. DISCUSSION s 1 Physiologic Effects Study * M Introduction This was a cross-sectional study of the relationship between selected physiologic parameters and PFOA exposure which was assessed using total serum fluorine. Participants were recruited from workers employed during November, 1990 in the Chemical Division of the 3M Chemolite Plant in Cottage Grove, Minnesota. All current workers who had worked in high exposure jobs at any time in the five previous years were invited to participate. A sample of workers employed in low exposure jobs was frequency matched to the age distribution of workers in high exposrue jobs. Participants completed a corporate medical history questionnaire and had vital parameters measured by an occupational health nurse. Blood was drawn for assays of total serum fluorine, seven hormones involved in the hypothalamicpituitary-gonadai axis, serum lipids, lipoproteins, hepatic function param eters, and hematology indices. Blood was drawn in the morning after workers were assigned to the day shift for at least three days. In 93% of participants serum fluorine levels were at least 10 times the background levels in the general population and in 3M workers not employed at Chemolite. Many workers who lacked PFOA exposure by job history had elevated PFOA levels. The sources of the unexpected PFOA exposure are unknown. 5.1.2 Hormones The findings from this study are consistent with the hypothesis that perfluorooctanoic add (PFOA) affects the human hypothalamic-pituitary-gonadal axis. This study showed that relatively tow levels of serum PFOA (20pM ) depressed free testosterone and elevated estradiol but did no affect LH or FSH levels. The assodation between free testosterone and PFO A was Afferent in 198 3MA00749595 p. 31 older men than in younger men. In older men, free testosterone (FT) was depressed below 1 0 ng/ml at serum fluoride levels below one part per million (estimated PFOA levels below 1 pM ). In younger men, FT decreased toward 10 ng/mi at serum fluoride levels above 15 ppm (estimated PFOA levels below 15 pM). Increasing age may increase men's susceptibility to the testosterone lowering effects of PFOA. The associations between PFO A and the hormone levels may reflect a true causal relationship, or may be a result of chance, bias, or uncontrolled confounding. There are no human studies of PFO A associated reproductive toxicity available for comparison. Studies of the effects of PFOA in rodents have demonstrated a similar decrease in testosterone, increase in estradiol, and little change in L H 19 The association between PFOA and free testosterone may have been mediated by elevated estradiol and prolactin. Elevated estradiol decreases testosterone and other steroid hormone synthesis in Leydig cells. LH response to low testosterone is attenuated by estradiol through negative feedback mechanisms at the pituitary and hypothalamic levels112> 113. Elevated prolactin sensitizes the hypothalamus and pituitary to estrogens feedback. The combined effect of elevated estradiol and prolactin could have reduced the secretion of LH and the subsequent Leydig cell response. Estradol has direct effects on Leydig cell testosterone synthesis. In rats, PFOA decreased androstenedione and testosterone, but not 17 alpha-hydroxyprogesterone18. The metabolism of 17 alpha-hydroxyprogesterone to androstenedione was inhibited at the step of the 0 1 7 ,2 0 lyase. The activity of the rate limiting 0 1 7 ,2 0 lyase has been reported to be under estradiol regulation in rat Leydig c e lls 114* 11S. Thus, in PFOA treated rats, elevated levels of estradiol may inhibit the 0 1 7 ,2 0 lyase and thereby reduce testosterone synthesis. The increase in the estradiol-testosterone ratio observed in workers is compatible with this mechanism for decreased free testosterone. The primary source of estradiol in males is the P450 (P 450 19) mediated aromatization of testosterone 116,117. Additional estradiol is secreted directiy from Leytfg cells. The observed increase in estradiol may be the result of increased production from one of these two sources or may be the result of inhibition of P450 mediated estradiol m etabolism 118. Perfluorooctanoic acid, a 199 3M A00749596 p. 32 51. Beiisle J, Haben D. A method for determining perfluorooctanoic add in blood and other biological samples. Anal Biochem 1980;101:369-376. 52. Klevens H, EHenborgen . Pnotein-fluoroadd Interaction. Discuss Faraday Soc 1954;18:277-289. 53. Klevens H. Nature 1955;176:879. 54. YOnen M . Hanhijarvi H, Jaakonaho J, Peura P. Stimulation by estracflol of the urinary excretion of perfluorooctanoic ad d in the mate ra t Pharmacol Toxicol 1989:65:274-277. 55. Hanhijarvi H, YOnen M , Kojo A, Kosma U. Elimination and toxicity of perfluorooctanoic add during subchronic administration in W istar rats. Pharmacol and Toxicol 1987;61:66-68. 56. Venkateswartu P. Determination of total fluoride in serum and other biological materials by oxygen bomb and reverse extraction techniques. Anal biochem 1975,158:368-377. 57. Nordby G , Luck J. Perfluorooctanoic ad d interactions with human serum albumin. J Biol Chem 1 9 5 6 2 1 9 :2 6 6 . 58. Johnson J, Gibson S, O ber R. Cholestryamine-enhanced fecal elimination of carbon-14 in rats after administration of ammonium [14C]perfluorooctanoate. Fundament Appl Toxicol 1984;4:972-976. 59. Johnson J. Extent and route of excretion and tissue distribution of total carbon-14 in male and fem ale rats after a single IV dose of F C -1 4 3 .1980, Riker Laboratories: 60. Pastoor T , Lee K, Perri M, Gillies P. Biochemical and morphological studies of ammonium perfluorooctanoate-induced hepatomegaly and peroxisome proliferation. Exp Mol Pathol 1987;47:98-109. 235 3MA00346185 TABLE A4.1.21 FOLLICLE STIM ULATING HORM ONE T O PROLACTIN RATIO (FS H /P ) BY BODY MASS IN D EX, AG E, SMOKING AND DRINKING STATUS 1990 PERFLUOROCHEMICAL EFFECTS STUDY. 3M C H EM O U TE PLANT. COTTAGE GROVE, M INNESOTA ___ - N MEAN SO M EDIAN RANGE TE S T# BMI <25 25-30 >30 40 0.72 0.51 0S7 0.2-21 F-22 56 0.79 0.52 0.65 0.1-26 M 17 0.74 0.58 0.57 0.2-26 AGE <31 31-40 41-50 51-60 20 0.46 0.23 0.45 0.2-1.0 F-5.41 48 0.71 0.51 04 0.1-2.6 P-.002 26 0.88 00 0.73 0.2-2.1 19 1.05 0.62 0,81 0.2-2.6 A lcohol <10Z/d 86 0.81 057 0.66 02-21 F-3.18 1-3oz/d 19 0-57 0.32 0.50 0.1-26 p-.oa missing 8 0.66 OJI 0.60 02-26 Tobacco smoker nonsmoker missing 27 84 2 1.00 0.57 0.79 0.3-26 F-7.90 0.68 0.49 0.51 0.1-26 P-.006 0.75 0.57 0.62 0.3-1.2 TOTAL ns #univariate Anova 280 3MA00346230 APPENDIX-3 TABLES OF HORMONE RATIOS BY TOTAL SERUM FLUORIDE 281 3MA00346231 TABLE A4.2.1 HORMONE RATIOS BY TOTAL SER U M FLU O R ID E: ESTRADIOL/FREE TESTO STERO NE (E/TF) ESTRADIOUBOUND TESTO STRO NE (E/TB) ESTRADIOL/THYROID STIM ULATING HORM ONE (E/TSH ) 1990 PERFLUOROCHEMICAL EFFECTS STUDY, 3M CHEM OUTE PLANT. COTTAGE G R O VE, M INNESO TA TOTAL FLU O R ID E ppm <1 > = 1 -3 >3-10 >10-15 >15-26 TOTAL N 23 64 15 6 5 113 <1 >=1-3 >3-10 >10-15 >15-26 TOTAL 23 64 15 6 5 113 <1 >=1-3 >3-10 >10-15 > 1 5 -2 6 TOTAL 23 64 15 6 5 113 #univariate Anova MEAN 2.5 2.1 23 2 .6 2.7 2.25 73 5.9 6.7 6.9 63 6.4 293 24.9 26.7 19.3 19.8 25.5 SD M EDIAN RANGE E /T F TEST# 13 0.8 0.6 1.1 0.7 .92 E/TB (X100) 35 25 2.8 2.8 1.8 2.8 E/TSH 21.8 133 16.7 1.9 6.8 15.6 23 1.9 23 2.1 3 31 63 55 5.9 5.6 5.3 5.8 215 23.6 21.1 153 16.9 213 0.7-53 0.8-5.4 0.8-33 1.6-4.0 1.9-33 0.7-54 F -1.65 p-,16 1.1-14.4 1.7-135 25-12.3 43-11.7 4.8-84 13-14.4 F-1.17 p -33 10.4-108.1 15523 3.9-59.0 75-45.8 15.2-315 1.76-108.1 F-0.75 p-56 282 3MA00346232 TABLE A 4.2.2 HORM ONE RATIOS BY TOTAL SER U M FLU O R ID E: BOUND TESTO STERO NE/FREE TESTO STRO NE (TB /TF) BOUND TESTO STRO NE/FO LUCLE STIMULATING HO RM O NE (B /F S H ) BOUND TESTOSTERONE/PROLACTIN (TB/P) FR EETESTO STER O N E/PR O LA C TIN fTF/P) 1990 PERFLUOROCHEM ICAL EFFECTS STU D Y. 3M CH EM O U TE PLANT, COTTAGE GROVE. M INNESO TA TOTAL FLUORIDE PPm >3-10 >10-15 >15-26 TOTAL N 23 64 15 6 5 113 <1 >=1-3 >3-10 >10-15 >15-26 TOTAL 23 64 15 6 5 113 <( " >3-10 >10-15 >15-26 TOTAL 23 64 15 6 5 113 <1 >=1-3 >3-10 >10-15 >15-26 TOTAL 23 64 15 6 5 113 #urivaliate Anova MEAN 36.7 36.8 34.5 383 43.6 36.8 148.3 130.9 135.3 122.7 162.9 136.1 82.1 87.5 86.4 515 90.3 845 2.34 2.38 2.64 1.40 2-20 2.35 SD M EDIAN RANG E TEST# TB /TF 9.6 9.6 74) 7.6 10.6 94! TB /FSH 85.6 76.3 81.4 4843 76.4 77.1 TB /P 43 81.2 51.0 27.9 30.6 67.3 T F /P 1.46 1.97 1.84 0.82 0.91 1.78 37.1 35.6 33.3 38.9 39.9 37.0 120.4 114.2 86.9 135.8 143.5 120.0 16.7-62.6 19.2-58A 25.0-43.6 29.3-47.6 36.9-62.4 16.7-6245 F-.94 P-.45 c-IOvs >10 T-2.10 P-.15 56.7-411.0 23.1-347.7 49.0-303J 34.4-169.8 67.1-2535 23.1-411.0 F-.40 P-.81 67.5 19.8-2055 F-.40 63.3 23.0-624.2 P-.81 78.0 28.1-224.2 52.1 22^-89^ 83.4 58.3-129.7 70.7 19.8-624.2 2.01 .7-7.8 F-.52 138 .6-15.0 P-.72 2.40 41-8.1 14J5 5-2.3 2.18 >3.5 1.95 >15.0 283 3MA00346233 3M PFOS-PFOA - Human Health and the Environment Page 1 of 4 S earch 3M .co m : United S Products & Services Brands Technologies O ur Com pany____ Partners & S u p p l i e r s _____ ___ PFOS-PFOA Inform ation W h a t is 3M Doing? Human Health and the E n viro nm ent Report on Drinking W ater Near 3M Plants United States > Our Company > Sustainability > 3M PFOS-PFOA > Human Health an En viro nm ent .. .......... Human Health and the Environment Human Health PFOS and PFOA are extremely well-researched materials. This research has been conducted by 3M and other scientists around the world. The extensive research to date shows no adverse human health effects resulting from exposure to PFOS or PFOA. This is supported by observational research involving thousands of 3M production employees. That research was conducted by 3M and by the University of Minnesota under grants from 3M. In all of our years of research we have not found any evidence of adverse health effects in our employees. Over 25 years of medical surveillance of exposed employees failed to identify any health effects attributable to exposure to PFOA or PFOS. It is important to note that employees working directly with these materials in a manufacturing facility have much higher exposure than that found in the general population. These studies and medical surveillance results have been published in peer-reviewed scientific journals and shared with the EPA and with regulatory agencies in other countries. A bibliography of these studies can be downloaded below. Related Links City of Oakdale: iwwwci oakdale. City of Lake Elm wwwlakeelmo.c LateJElmoJ^ew! Water Report (PDF. 2294 KB) MDH: ymwjteaMvsM Perfluorochemic (PDF, 32 KB) MPCA: www p c a .s ta te .r Perfluorochemic Present and Fut (PDF, 64 KB) EPA: www.eoa.oov Perfluorooctanoi 3M Sustainabilit www 3m.com/si Reference: 3M Employee Medical Studies (PDF, 26 KB) In addition to research of the exposure of 3M's production employees who worked closely with these materials, the company has studied the low level presence of these materials in the general population. Along with our employee research, these studies have also been published in scientific literature. A bibliography of these studies can be downloaded below. Reference: 3M General Population Exposure (PDF, 13 KB) Interim results of a study being conducted by the University of Pennsylvania are consistent with the results of 3M's own studies of its production employees. The University of Pennsylvania study, funded by a National Institute of Health Environmental Justice grant, is evaluating the health of residents of Little Hocking, Ohio who have been exposed to elevated levels of PFOA in their drinking water as the result of releases from a different company's manufacturing plant. The study's principal investigator is University of Pennsylvania School of Medicine Professor Dr. Edward Emmett, who is board certified in occupational medicine and http://solutions.3m.com/wps/portal/3M /en_US/PFOS/PFOA/Information/Health-Environm... 5/26/2006