Document dEMK9p7mYZEdqwveE7qKr9Mq

Corporate Health Physics Corporate Occupational Medicine Corporate Product Responsibility Corporate Toxicology 3M Medical Department 3M Center, 220-2E-02 PO Box 33220 St. Paul, MN 55133-3220 651 733 1110 ft R13&CM3 Deterimination of Serum Elimination Half-Lives of Ammonium Perfluorooctanoate, Perfluorooctane Sulfonic Acid, Perfluoroheaxane sulfonic acid and Total Organic Fluorine in Decatur Chemical Plant Retirees The objective of this study is quantitate the human serum elimination half life of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), perfluoroohexanesulfonate (PFOS) and total organic fluorine (TOF). Blood will be collected biannually from approximately 25 retireed 3M Decatur employees for a period of 5 years. Upon collection and analysis of the third sample (baseline, 6 months and then 12 months) and thereafter, an interim draft half-life analysis report will be prepared. 000977 3M Company Page 1 of 19 PROTOCOL Epidemiology ,220-3W -05 Medical Department 3M Company St. Paul. MN 55144 Date: October 14, 1998 Title: DETERMINATION OF SERUM ELIMINATION HALF-LIVES OF AMMONIUM PERFLUOROOCTANOATE, PERFLUOROOCTANE SULFONIC ACID, PERFLUOROHEXANE SULFONIC ACID AND TOTAL ORGANIC FLUORINE IN 3M DECATUR CHEMICAL PLANT RETIREES. Study Start Date: Estimated Date of Final Report: IRB Approval Date: Protocol Number # 0007 IRB Approval # 98095 Exempt XX Expedited June, 2004 14 October 1998 Principal Investigator: Jean M. Burris RN, MPH Co-investigators: Geary Olsen, DVM, PhD1 John C. Schumpert MD Cathy Simpson, RN2 Jeffrey Mandel, MD, MPH1 Study Director:: Jeffrey Mandel, MD, MPH1 Study Sponsor: Medical Department 3M Company 220-3W-05 Saint Paul, MN 55144 1. Occupational Medicine, Medical Department, 3M Company, 220-3W-05, St. Paul, MN 55114 2. 3M Decatur Specialty Adhesives and Chemicals Plant, P.O. Box 2206, Decatur, AL 35609-2206 000978 3M Company Page 2 of 19 ABSTRACT 3M manufactures products which contain chemical compounds, either as intentional components or residual impurities, that have as a parent molecule, perfluorooctane sulfonyl fluoride (POSF). These compounds may be expected to transform metabolically, to an undetermined degree, to PFOS as an end-stage metabolite. Other compounds manufactured by 3M include ammonium perfluorooctanoate (PFOA) and perfluorohexane sulfonic acid (PFHS). These molecules enter a number of product applications (e.g., surfactants, food packaging additives, polymers). The biological elimination rates of fluorochemicals have been studied in rats, pregnant rats, female rabbits and hamsters. Biological half-lives have been calculated from the studies in rats and dogs. In addition, the half-life of serum total organic fluorine in a fluorochemical worker was estimated using serial collections of serum total organic fluorine. These studies reveal that PFOS and PFOA may persist in the body for prolonged periods, and with continuing exposure, accumulate over time in biological systems. To date, the actual elimination half-life of perfluorooctane sulfonate (PFOS), ammonium perfluorooctanoate (PFOA), perfluorohexane sulfonic acid (PFHS), and total organic fluorine (TOF) in human serum is not completely understood. The objectives of this study are to quantitate the elimination half life in human serum of PFOA, PFOS, PFHS, and TOF. These half -lives will be calculated from declines in serum fluorochemical levels in 3M Decatur Chemical Plant Retirees. 000979 INTRODUCTION 3M Company Page 3 of 19 3M manufactures products which contain chemical compounds, either as intentional components or residual impurities, that have as a parent molecule, perfluorooctane sulfonyl fluoride (POSF). These chemicals include: perfluorooctane sulfonate (PFOS), N-ethyl periluorooctanesulfonamide, N-ethyl perfluorooctanesulfonamido ethanol, N-methyl periluorooctanesulfonamido ethanol and chemicals derived from it, and the mixture of mono-, di- and tri [N-ethyl perfluorooctane sulfonamidoethyl] phosphates. There may be other precursors in the workplace, including perfluorohexanesulfonyl fluoride (PHSF). These molecules enter a number of product applications (e.g., surfactants, food packaging additives, polymers). These compounds may be expected to transform metabolically, to an undetermined degree, to PFOS (and PFHS) as an end-stage metabolite. Potassium perfluorooctane sulfonate (CgFnOS02K+) is itself, a surfactant used as a wetting and foaming agent in industrial and commercial processes. (Olsen, et al., 1998) Subchronic studies in rats and primates suggest there may be a potential for cumulative toxicity with PFOS over time with the primary effect related to metabolic wasting. These molecules have long elimination half lives in biological systems. Although the mechanism of toxicity is not fully understood, toxicity may be due to an effect on peroxisome proliferation, fatty acid metabolism, membrane function, protein synthesis and/or mitochondrial bioenergetics. (Olsen, et al., 1998) The biological elimination rates of fluorochemicals have been studied in rats, pregnant rats, female rabbits and hamsters. Biological half-lives have been calculated from the studies in rats and dogs. In addition, the half-life of serum total organic fluorine in a fluorochemical worker 000980 3M Company Page 4 of 19 was estimated using serial collections of serum total organic fluorine. These studies reveal that PFOS and PFOA may persist in the body for prolonged periods, and with continuing exposure, accumulate over time in biological systems. To date, the actual elimination half-life of perfluorooctane sulfonate (PFOS), ammonium perfluorooctanoate (PFOA), perfluorohexane sulfonic acid (PFHS), and total organic fluorine (TOF) in human serum is not completely understood. The objectives of this study are to quantitate the elimination half life in human serum of PFOA, PFOS, PFHS, and TOF; these half lives will be calculated from declines in serum fluorochemical levels in 3M Decatur Chemical Plant Retirees. This information is necessary in order to; 1) plan the most appropriate periodicity of medical surveillance and 2) guide medical decision making of workers from fluorochemical production facilities when those workers' serum fluorochemical levels are determined to be unsafely elevated. A benefit of this research will be to understand the natural history of fluorochemical excretion. LITERATURE REVIEW AMMONIUM PERFLUOROOCTANOATE (PFOA or FC-143) Excretion rates of PFOA have been observed in rats, and found to be different by gender and route of excretion. Following single i.v. doses of 14C-FC-143 (carbonyl carbon labeled) in rats, Johnson et al, found that females excreted virtually all the administered 14C within 1 day. Urinary excretion for males was about 50% of the dose by day 6 and 83% by day 36. Fecal I4C excretion for females was 1.5% by 3 days and for males was 5.4% by 36 days. (Johnson, et al., 000981 3M Company Page 5 of 19 1980) Rapid urinary excretion of l4C following oral doses of l4C-FC-143 was also shown to occur in pregnant rats. (Johnson, et al., 1983) Excretion rates vary by species studied. Excretion of radiolabeled PFOA was studied in four species by Dupont in 1988. Excretion as a percentage of administered dose 120 hours after dosing was in the following order; female rat, male and female rabbit and male hamster (> 99%); female hamster (60%); male rat (39%); male and female mice (21%). (Dupont, 1988) Of note, the administered dose and routes of exposure and excretion were not specified in this study report. Rats and dogs respond to pharmacologic interventions that change PFOA excretion rate. In male rats administered single i.v. doses of 14C-FC-143 (carbonyl carbon labeled) cholestyramine (4% w/w in feed) increased cumulative 15 day fecal ,4C excretion 9.8-fold versus controls. Total ,4C excretion (feces plus urine) was also enhanced, although less dramatically (84.3% of dose vs. 71.8% for controls). (Johnson, et al., 1980a; Johnson JD, et al., 1984) There is no difference between the renal clearances of 14C in male and female dogs either before or after probenecid. Probenecid significantly reduces PFOA clearance in dogs. Glomerular filtration rates of PFOA were similar in rats and dogs. (Hanhijarvi, et al., 1988) Elimination half-life has been calculated under numerous conditions in rats and dogs. The results show the same differential elimination rate in rats by gender (i.e., female > male), as well as halflife differences by route of exposure and species. Following a single oral dose of 14C-FC-143 (carbonyl carbon labeled) in male rats, the plasma half-life was 4.8 days. (Johnson, et al., 1979) 000982 3M CompanyPage 6 of 19 In female rats administered oral or i.v. doses of l4C-FC-143 (carbonyl carbon labeled), over 90% of the administered dose was recovered in the urine within the first 12 hours. The whole body elimination half-life of PFOA in male and female rats was 15 days and less than one day, respectively, following a single 4-mg/kg intraperineal dose. (Vanden Heuval, et al., 1991) (Johnson, et al., 1983; Johnson, et al., 1980) The half-life of PFOA in the liver was 60 hours for females and 210 hours for male rats. (Ylinen, et al., 1990) The decreased excretion rate (i.e., increased elimination half-life) in males is seen across at least two species: rats (as above) and dogs. The plasma half-life of PFOA was longer in male dogs (473 to 541 hours) than in females (202 to 305 hours). (Hanhijarvi, et al., 1988) The elimination half-life appears to be similar in male rats exposed to either inhalational or dermal exposure. Following repeated inhalation exposures to FC-143 over a two-week period, blood organic fluoride levels in male rats showed a half-life of five to seven days. (Kennedy, et al., 1986) A blood half-life of five to seven days was seen following repeated dermal exposures in male rats. (Kennedy, 1985) A calculation of the elimination half-life of an organic fluorine species has been reported in the human. The half-life of total serum organic fluorine in a fluorochemical worker who was removed from further exposure was greater than 18 months. This worker had a blood organic fluorine level of 40 parts per million over the period of one year. The worker's organic fluorine level rose to 70 parts per million for no apparent reason. The worker was then removed from the fluorochemical production area and his blood and urine samples were periodically checked for organic fluorine and PFOA over an 18-month period. A total of 18 months transpired before the 000983 3M Company Page 7 of 19 worker's blood organic fluorine level had returned to its base line of 40 parts per million. (Ubel, et al. 1980) Other estimates of serum fluorochemical half-lives have been calculated in the one thousand day range. 'F This anecdotal account does not actually track the serum PFOA level, but rather the serum total organic fluorine (TOF) level. It was found through empirical means that 90% of the blood organic fluorine existed as PFOA. (Ubel, et al. 1980) PERFLUOROOCTANE SULFONIC ACID (PFOS or FC-95) Perfluorooctane sulfonic acid appears to persist in biological systems, being excreted more slowly than PFOA. Single i.v. doses (mean 4.2 mg/kg) of 14C-FC-95 and 0.9% NACL were administered to male rats. By 89 days after dosing, 30.2% of the administered I4C had been excreted in the urine and 12.6% had been excreted in the feces. (Johnson, et al., 1979) Pharmacologic interventions do appear to increase the excretory rate of PFOS. Fecal and total excretion of 14C were markedly increased in male rats administered Cholestyramine (about 2.7 gm/kg per day) and their diet following single i.v. doses of 14C-FC-95. The results suggest that there was significant enterohepatic circulation of FC-95. (Johnson, et al., 1980a; Johnson, et al., 1984) Much less is known concerning elimination half-life of PFOS than PFOA; only one calculation of the elimination half-life of PFOS has been attempted. The plasma elimination half-life of 14C following single oral administration of 14C-FC-95 (mean dose 4.2 mg/kg) to male rats was 7.5 days. (Johnson, et al. 1979a) 000984 Mandel, J. Personal communication. 3M Company Page 8 of 19 000985 RESEARCH METHODS 3M Company Page 9 of 19 The overall research design is prospective in nature, obtaining multiple serial blood samples from retirees throughout the course of a five-year period. We will track the decline in several serum fluorochemical levels in humans. The health outcomes that will be documented in this study are the half-life determinations of serum ammonium perfluorooctanoate (PFOA), periluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHS), and serum total organic fluorine (TOF). High-performance liquid chromatography mass spectrometry/mass spectrometry will be utilized to analyze all serum samples. The accuracy and reliability of this device will be the state of the art at the time of analysis. Periodically, split samples from one or two subjects will be utilized to assess reliability of the analysis. Only individuals who have retired from 3M Decatur chemical plant from the 1st of January 1995 through the 1st of January 1998, will be included in the study. Using information received from the Human Resources Department of 3M Decatur, 34 individuals were identified to have retired during this time period. Of the 34 individuals identified, 7 have previously been enrolled in the fluorochemical medical surveillance program. Four of these individuals participated in the medical surveillance program in 1994 but not 1997; 3 individuals participated in 1997 only. We will attempt to enroll all 34 retirees into the study. Future retirees will not be enrolled. Serum fluorochemical levels will be drawn every six months. All serum fluorochemical levels will be drawn within a one-month time frame (i.e., within one month of March and September). 000986 3M Company Page 10 of 19 Retirees will be recruited to the study through first, an introductory letter and second, a phone conversation from the principle investigator or his designee. Subsequent to the follow-up telephone conversation and if the retiree is willing to enter the study, a written informed consent form (Appendix A) and a medical questionnaire (Appendix B) will be sent to the retiree for his review. Once the retiree signs the consent form, completes the questionnaire, and returns the documents to the principle investigator, he will be entered into the study and scheduled for blood collection. Participation in the study is voluntary and retirees may drop out at any time. Blood collection will be scheduled biannually, in April and October (to not conflict with Holiday and summer vacation travel). Letters announcing blood collection dates and times will be sent out to each study subject one month prior to each blood collection month. Retirees will update their medical questionnaire at each blood collection. All blood collections will be performed under the supervision of the 3M Decatur plant nurse, Cathy Simpson, RN. Two red-topped tubes will be obtained from each retiree; the 3M Occupational Medicine Service methodology for handling and shipping of fluorochemical blood samples will be applied to all blood samples. Samples will be analyzed by the 3M Environmental Laboratory or its designated contract laboratory. Retirees will receive written reports of their serum fluorochemical levels following each blood collection cycle. Two methods of calculating the serum fluorochemical half life will be utilized. In the first method, a one compartment model will be assumed and the formula q, = qo (0.5f'/! 000987 3M Company Page 11 of 19 will be utilized to estimate the half life of elimination for PFOS, PFOA, PFHS, and TOF. The terms q, and q0 refer to the serum concentrations at time t and time 0, t is the elapsed time; t>/: is what we seek to solve. The second method will be used to verify the first. It also assumes a one compartment model. Each retiree's fluorochemical levels will be graphed on a log-linear scale as serum fluorochemical vs. elapsed time from to (in months) and entered into a database. Statistical analysis will be performed to determine the best-fit model that describes the slope of the loglinear line. (Appendix C) The slope of the log-linear line is related to the elimination constant (-kei) through the equation Slope = -Jcei(2.303) Once the elimination constant is calculated, the half life can be calculated using the relationship h/2= 0.693/kei Elimination half lives for TOF, PFOS, PFHS, and PFOA will be determined. (Benez, et al. 1985, Medinsky, et al. 1996.) DISCUSSION There are a number of limitations associated with the study, including: 1. The lack of pre-study serum fluorochemical levels in the majority of retirees, making it impossible to develop baseline levels for the majority of the study group. The tO values will therefore need to be their first fluorochemical level post-retirement. 0009S8 3M Company Page 12 of 19 2. Previous studies have performed serum total organic fluorine levels and not serum testing specific for serum PFOS or PFOA; comparability with previous work is thereby compromised. 3. Retirees on medications such as colestipol or cholestyramine, which can artificially increase the rate of elimination of fluorochemicals from the blood will artificially increase the elimination in unpredictable ways, thereby causing an underestimation of the elimination half life in the entire study population. 4. Retirees may unknowingly have medical conditions that will decrease their toxicant elimination rate unpredictably (e.g., renal failure, congestive heart failure, cholelithiasis, etc.), thereby causing an inaccurate estimation of the elimination half life in the entire study population. For these reasons, the study will occur over the protracted period of five years instead of a shorter time period (i.e., three years). As the only human data plotting total organic fluorine suggest plasma elimination half-life of 18 months, a three year study would allow for verification of that estimate since three years would be equal to two half-lives. A five-year study, therefore, should include over three half-lives of elimination, and make it possible to use several years' data to calculate the elimination half life. The overall results collected in this study may be used in publications or in public presentations. Retiree names or other individual data will not be revealed in any publication or other documentations intended for public examination. Individual results will be communicated only to the retiree. Individual results will be considered confidential information and will not be disclosed to anyone outside of the 3M Medical Department without the retiree's written consent. 000989 3M Company Page 13 of 19 Quality assurance will be performed per the guidelines set forth in the standard operating procedure for the creation, review, and approval of 3M epidemiology study protocols. Archiving of study materials, upon completion of the study, will be performed per the standard operating procedure for the creation, auditing, review and approval of 3M epidemiology final reports. The study will be communicated to the retirees, management, and the technical community. Communications to the retirees will be in the form of a letter, which states the retiree's various blood fluorochemical levels. These letters will be sent out following each blood draw. Communication to management will be in the form of a written document which will undergo the review process as set forth in the standard operating procedure for the creation, auditing, review and approval of 3M epidemiology final reports. The communication to the technical community will be in the form of a scientific paper, which will be submitted to a relevant peer reviewed scientific publication. 000990 REFERENCES 3M Company Page 14 of 19 1. Olsen GW, Burris JM, Mandel JH, and LR Zobel. An epidemiologic investigation of clinical chemistries, hematology and hormones in relation to serum levels of perfluorooctane sulfonate in male fluorochemical production employees. J Occup Environ Med 1998; 2. Johnson JD and Ober RE. Extent and route of excretion and tissue distribution of total carbon-14 in male and female rats after a single IV dose of FC-143-14C. Riker Laboratories, Inc. St., Paul, MN; 1980. 3. Johnson JD and Conard GJ. Extent and route of excretion of total carbon-14 in pregnant rats after a single oral dose of ammonium ,4C-perfluorooctanoate. Riker Laboratories, Inc., St. Paul, MN; 1983. 4. Vanden Heuval J, Kuslikis B, Van Refelghem M, and Peterson R. Tissue distribution, metabolism, and elimination of perfluorooctanoic acid J Biochem Toxicol 1991; 6:83-92. 5. DuPont. Ammonium perfluorooctanoate. Toxicity Hazard Information from MSDS; 1988. 6. Johnson JD and Ober RE. Enhanced elimination of FC-95-14C and FC-143-,4C in rats with cholestyramine treatment. Riker Laboratories, Inc., St. Paul, MN, 1980a. 7. Johnson JD, Gibson SJ, and Ober RE. Cholestyramine-enhanced fecal elimination of carbon14 in rats after administration of ammonium [14C]perfluorooctanoate or potassium[14C]perfluorooctanesulfonate. FundAppl Toxicol 1984; 4:972-976. 8. Griffith FD and Long JE. Animal toxicity studies with ammonium perfluorooctanoate. Am Ind Hyg Assoc J 1980; 41:576-583. 9. Hanhijarvi H, Ylinen M, Haaranen T and Nevalainen T. A proposed species difference in the renal excretion of perfluorooctanoic acid in the beagle dog and the rat. In: Beynen AC and Solleveld HA, eds. New Developments in Biosciences: Their Implicationsfo r Laboratory Animal Science. Martinus Nijhoff, Dordrecht, 1988. 10. Gilliland FD. Fluorocarbons and human health: studies in an occupational cohort. Ph.D. Dissertation, U. of Minnesota, Minneapolis, MN; 1992. 11. Johnson JD and Ober RE. Absorption of FC-143-14C in rats after a single oral dose. Riker Laboratories, Inc., St. Paul, MN; 1979. 12. Johnson JD and Ober RE. Extent and route of excretion of total carbon-14 pregnant rats after a single oral dose of ammonium 14-C perfluorooctanoate. Riker Laboratories, Inc., St. Paul, MN; 1983. 000991 3M Company Page 15 of 19 13. Kennedy GL, Jr., Hall GT, Battelli MR, Barnes JR, and Chen HC. Inhalational toxicity of ammonium periluorooctanoate. Fund Chem Toxicol 1986; 24:1325-1329. 14. Kennedy GL, Jr. Dermal toxicity of ammonium perfluorooctanoate. Toxicol Appi Pharmacol 1985; 81:348-355. 15. Ylinen M, Kojo A, Hanhijarvi H, and Peura P. Disposition of perfluorooctanoic acid in the rat after single and subchronic administration. Bull Environ Contam Toxicol 1987; 44:46-53. 16. Ubel FA, Sorenson SD, and Roach DE. Health status of plant workers exposed to fluorochemicals, a preliminary report. Am Ind Hyg Assoc J 1980; 41:584-589. 17. Johnson JD, Gibson SJ, and Ober RE. Extent and route of excretion and tissue distribution of total carbon-14 in rats after a single i.v. dose of FC-95-I4C. Riker Laboratories, Inc., St. Paul, MN; 1979. 18. Johnson JD and Ober RE. Absorption of FC-95-14C after a single oral dose. Riker Laboratories, Inc., St. Paul, MN; 1979a. 19. Benet LZ and Sheiner LB. Pharmacokinetics: The dynamics of drug absorption. Distribution, and elimination. In: Goodman Gilman A, Goodman LS, Rail TW, and Murad F, ed. Goodman and Gilman's The Pharmacologic Basis of Theapeutics, Seventh Edition. Macmillan Publishing Company, New York, 1985. 20. Medinsky MA and Klaasen CD. Toxicokenetics. In: Carasett and Doull's Toxicology: The Basic Science of Poisons, Fifth Edition. Klaasen CD, Amdur MO, and Doull J, editors. New York, McGraw-Hill, 1996. 000992 Appendix A 3M Company Page 16 of 19 CONSENT FORM FOR COLLECTION OF BLOOD FOR SERUM FLUOROCHEMICAL LEVEL HALF-LIFE DETERMINATION INTRODUCTION You and your colleagues were involved in fluorochemical production at 3M Decatur prior to your retirement. You are invited to participate in a research study being conducted by 3M Occupational Medicine Services regarding fluorochemicals. Your participation would involve donating one red-topped test tube of blood approximately every six months for the next five years. Your blood will only be tested for the amount and kind of fluorochemicals it contains; it will not be used to test for any other substances or disease. Please review this consent form carefully and be sure your questions are answered before you make a decision to participate. The plant nurse will be available to provide you with additional information at the time of your medical surveillance blood donation. PURPOSE OF STUDY The purpose of the study is to determine how much and what types of fluorochemicals are eliminated from the human body over time. STUDY PROCEDURES Your blood will be drawn with one needle stick and require two test tubes. This will occur about every six months for the next five years. A letter will be sent to you in advance informing you of the proper date, time, and place to report to for blood collection. POTENTIAL RISKS/BENEFTTS The only discomfort you may feel is from the needle stick. You may also have some temporary redness/bruising/swelling in this area after blood collection. BENEFTTS There will be no direct benefit from your participation in this study. However, the information gained from this study will further help us understand human exposures to fluorochemicals. Your individual results as well as the overall results will be communicated to you only. Your individual results will be considered confidential information and will not be disclosed to anyone outside the 3M Medical Department without your written consent. COMPENSATION If you suffer injury or a medical condition that appears to be the result of participating in this study, you will be referred to another health care professional at no cost to you. In the event of a research related injury, compensation will be determined on a case by case basis by 3M. 000993 3M Company Page 17 of 19 CONFIDENTIALITY The overall results collected in this study may be used in publications or public presentation. Your name will not be revealed in any publication or other documents intended for publication examination. Your individual results will be communicated to you only. Your individual results will be considered confidential information and will not be disclosed to anyone outside the 3M Medical Department without your written consent. SUBJECT RIGHTS/AVAILABILITY OF INFORMATION If you have any questions about the study now, or later, or in the event of a research related injury or emergency, contact Dr. Jeffrey Mandel (651-733-8670) or Jean Burris, R.N. (651-737-7867). For answers to questions about your rights in regard to this research, you may contact Dr. Larry Zobel, Chair, 3M Institutional Review Board at 651-733-5181. VOLUNTARY PARTICIPATION AND WITHDRAWAL Participation in this study is voluntary. Refusal to participate will involve no penalty of loss of benefits to which you are otherwise entitled. You are free to withdraw from the study at any time for any reason. The investigator may stop your participation in this study should it be determined that continued participation may be detrimental to your health. Following each semi-annual blood collection, you will receive a check for $50.00 as compensation for your time and effort. SUBJECT CONSENT By signing the consent form, I certify that I am at least 18 years old. I confirm that I have read. this consent form, and that I have been given adequate opportunity to ask any questions I may have about this consent form or the study. I also confirm that I understand the scope of my participation in this study, and that all of my questions have been answered to my satisfaction. I am signing this consent form voluntarily, and I desire to participate in the study. I understand that I will receive a copy of this signed consent form. I understand that I will receive a check for $50.00 immediately following each semi-annual collection of my blood. Signature Printed Name Witness Date 000994 Appendix B MEDICAL HISTORY QUESTIONNAIRE 3M Company Page 18 of 19 Please list the names of the ALL the medications you take at least once a day. Please circle the conditions you now suffer from or have suffered from in the last three years. Kidney Failure Gall Bladder Disease Hepatitis/Jaundice Congestive Heart Failure Liver Disease Inflammatory Bowel Disease Crohn's Disease Pernicious Anemia 000995 3M Company Page 19 of 19 Appendix C Example of a log-linear plot that will be used to estimate the serum fluorochemical elimination half life in Decatur retirees. 000996