Document vymBe2Lee45J7XLxmgp640kr6

---A TCCoorrppoorErataeteTPHaetaAot RSePhysicos n,ne 1oCuosneMse2$052183:032220 F=YAIR-202560-p0y0-0132078 So Htc Depriet VoL TI April 21, 2000 (81000000018) Attachments To April 21, 2000 Letter to C. Auer from W. Weppner (Medical Surveillance and Epidemiology) FinalReports 1. AnEpidemiologic Investigation ofClinical Chemistries, Hematology and Hormones in Relation to Serum LevelsofPerfluorooctanesulfonate in Male Fluorochemical Production Employees. [Included is a 3M reportofmedical surveillance data. Also included is a published paper from this 3M report.) 2. Fluorochemical Exposure (Serum) Assessment of (3M) Decatur Chemical and Film Plant Employees. [Includedare a 3M study protocol and report.] 3. Mortality StudyofEmployees at 3M Plant in Decatur, Alabama [Includedis a UniversityofMinnesota final report.] 4. Determination of Serum Fluorochemical Levels in Sumitomo 3M Employees [Included are a 3M study protocol and final report.] 5. AnalysisofSelected Decatur Employee Serum for Sulfonic and Carboxylic Fluorochemicals [Included is a 3M technical report.] 6. Fluorochemical Control Study [Included is a 3M reportofmedical surveillance data.] 7. Working Memorandum on Data Quality Assessment [Included is a Battelle Laboratory memorandum regarding the mean and rangeofperfluorooctanesulfonate sera sample data collected by 3M from current and historical human populations.) FEEEIE 0 & 001068 : CCoorrppoorraattee HOecaclutphatPihoynsailcsMedicine 3POMBCoenxt3e3r222200-202 Comm de Seon 5,BlMN51830020 D 3M Medical Department 3M An Epidemiologic Investigation of Clinical Chemistries, Hematology and Hormones in Relation to Serum Levels of Perfluorooctane Sulfonate in Male Fluorochemical Production Employees Following reportsofthe findingof organic fluorine in sera samples, a fluorochemical medical surveillance program began at 3M's Decatur manufacturing facility in the late 1970's. The surveillance program has generally consistedofannual or biannual tests of clinical chemistries, pulmonary function, blood counts and a biomonitor of fluorochemical exposure. A total organic fluorine measurement was routinely done until 1993. This measures the amount of fluorine that was covalently bound to carbon in the serum sample. When test data were available, a company physician reviewed each employee's results. These physicians did not, and have not, found abnormalities in individuals that they felt were related to fluorochemical exposure. That is, medical conditions, medications and lifestyle factors adequately explained the laboratory. `abnormalities (which one expects to find in this typeofprogram.) Beginning in 1994, the 3M Decatur (Alabama) plant medical surveillance program incorporated a serum measurementofperfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Total organic fluorine was not measured. A formal report was writtenofthe aggregate analyses conductedofthe medical surveillance clinical program data for the Decatur (Alabama) and Antwerp (Belgium) employees who voluntarily participated in 1994, 1995 and 1997. The findings from this aggregate 001069 analysis suggested that, among these participating Antwerp and Decatur male fluorochemical production employees, significant hematological, clinical chemistry and hormonal abnormalities were not associated with serum PFOS levels up to 6 ppm. It was not possible to derive inferences from the few employees with serum PFOS levels > 6 ppm. Limitationsof this study include its cross-sectional design, the voluntary `participation rates, the few subjects exposed at the highest levels, and the lower levels of serum PFOS measured among these employees compared to those estimated to cause effects in laboratory animals. Resultsof the hepatic and lipid clinical chemistry tests `were published in the JournalofOccupationalandEnvironmentalMedicine (199941:799-806). In the Springof2000, medical surveillance will again be offered to 3M fluorochemical production employees at the Antwerp and Decatur manufacturing sites. 001070 April 22, 1998 An Epidemiologic Investigation of Clinical Chemistries, Hematology and Hormones in Relation to Serum Levels of Perfluorooctane Sulfonate in Male Fluorochemical Production Employees. Geary W. Olsen, D.V-M., Ph.D. Jean M. Burris, RN., MPH. Jeffrey H. Mandel, M.D., MPH. Larry R.Zobel, M.D., MPH. Medical Department, 3M Company, 220-3W-05, St. Paul, MN 55144 Page | 001071 ABSTRACT 3M manufactures products which contain chemical compounds, either as intentional components or residual impurities, that have as a parent molecule, perfluorooctane sulfonyl fluoride. These chemicals include: perfluorooctane sulfonate (PFOS), N-ethyl perfluorooctanesulfonamide, N-ethyl perfluorooctanesulfonamido ethanol, N-methyl perfluoroctanesulfonamido 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. 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 as an end-stage metabolite. Potassium perfluorooctane sulfonate (CsF170SO:K") is, itself, a surfactant used as a wetting and foaming agent in industrial and commercial processes. `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. Although the mechanism of toxicity is not fully understood, toxicity may be due 0 an effect on peroxisome proliferation, fatty acid metabolism, membrane function, protein synthesis and/or mitochondrial bioenergetics. Medical surveillance has been routinely performed on 3M fluorochemical production workers (in Decatur, Alabama and Antwerp, Belgium) with potential exposure: to PFOSand/orto perfluorinated precursors that may metabolically degrade to PFOS. `The purpose of this study was to provide an analysis of the hematology (hematocrit, hemoglobin, redbloodcells, white blood cells and platelet count), clinical chemistries. Page2 001072 (alkaline phosphatase, gamma glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, total and direct bilirubin, blood urea nitrogen, creatinine, glucose, cholesterol, low density lipoproteins, high density lipoproteins and triglycerides) and hormonal parameters (cortisol, dehydroepiandrosterone sulfate, estradiol, follicle stimulating hormone, 17-alpha hydroxyprogesterone, luteinizing hormone, prolactin, sex hormone binding globulin, free testosterone, bound testosterone, and thyroid stimulating hormone) in relation to serum PFOS as determined by high performance liquid chromatography mass spectrometry methods. These relationships were assessed in fluorochemical production employees from two time periods, 1995 (N = 178) and 1997 (N= 149). Descriptive simple and stratified analyses, Pearson correlation coefficients, analysis of variance and multivariable regression wereusedto evaluate for possible associations between PFOS and each hematological and clinical chemistry test and hormonal assay. ~ Age, body mass index, current alcohol consumption (drinks per day) and cigarette use (cigarettes smoked per day) were potential confounding factors that were considered in the analyses. Multivariable regression models were fitted with PFOS analyzed as a continuous variable using linear as well as non-linear transformations in order to maximize the possibility of finding associations between PFOS and the parametersofinterest. Four categorizations of serum PFOS levels were assessed in relation to the response variables: 0 -< 1 ppm | - <3 ppm; 3 - <6 ppm: and 2 6 ppm. In 1995, mean serum PFOS levels by category were 0.49 ppm, 1.82 ppm, 4.12 ppm and 8.17 ppm, respectively. In 1997, mean serum PFOS levels by category were 0.52 ppm, 1.78 ppm, Page 3 001073 3.87 ppm and 7.20 ppm, respectively. For both years, 95 percent of the employees' serum PFO levels were below 6 ppm. Although the two plant populations differed by age, body mass index and alcohol consumption, no consistent associations, by both plant locations and year, were observed between the clinical chemistries, hematology and hormone parameters and the employees' serum PFOS levels. `The findings from this study suggest that, among these Antwerp and Decatur male fluorochemical production employees, significant hematological, clinical chemistry and hormonal abnormalities are not associated with serum PFOS levels up to 6 ppm. It is not possible to derive inferences from the few employees with serum PFOS levels 2 6 ppm. Limitations of this study include its cross-sectional design, the voluntary participation rates, the few subjects exposed at the highest levels, and the lower levels of serum PFOS measured among these employees compared to those that caused effects in laboratory animals. paged 001074 INTRODUCTION 3M manufactures products which contain chemical compounds, cither as intentional components or residual impurities, that have as a parent molecule, perfluorooctane sulfonyl fluoride. These chemicals include: perfluorooctane sulfonate (PFOS), N-cthyl perfluorooctanesulfonamide, N-ethyl perfluorooctanesulfonamido ethanol, N-methyl perfluoroctanesulfonamido 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. These molecules entear number of product applications (e.g., surfactants, food packaging additives, polymers). These compounds can be expected to be transformed metabolically, to an undetermined degree, 10 PFOS as an end-stage metabolite [Gibson et al., 1983]. Potassium perfluorooctane sulfonate (CsFi7OSO;K") is, itself, a surfactant used as a wetting and foaming agent in industrial and commercial processes. Potassium perfluorooctane sulfonate is readily absorbed by ingestion [Johnson and Ober, 1979; O'Malley and Ebbens, 1980]. Ninety five percentof a single oral dose of [!C] PFOS administered to male rats was absorbed within 24 hours [Johnson and Ober, 1979]. After a single, 24-hour occluded dermal exposure to PFOS at a dose of 5000 mg/kg, total serum organic fluorine concentrations were 10.3 and 0.9 ppm for male and female albino rabbits, respectively [O'Malley and Ebbens, 1980]. Twenty eight days after dosing, total serum organic fluorine concentrations had risen to 130.2 and 128.0 `ppm for male and female albino rabbits, respectively. On the other hand, no quantifiable Page 001075 organic fluorine could be detected 28 days after a single, 24 hour occluded dermal exposure to a 0.06% solution of PFOS in water at doses of 0, 0.003, 0.06, and 0.3 mg. PFOS solution/kg, respectively, to 3 male and 3 female albino rabbits per dose group (Glaza, 1995]. Once in the body, PFOS concentrates primarily in the liver of rats [Johnson et al., 1979]. Eighty-nine days aftera single intravenous dose (mean 4.2 mg/kg) of radiolabeled PFOS, mean tissue concentrations (ig PFOS equivaleng tissue) were: liver, 20.56; plasma, 2.21; kidney, 1.09; lung, 1.06; spleen, 0.51; bone marrow, 0.46; red blood cells, 0.45; adrenals, 0.41; testes, 0.36: skin, 0.35; muscle, 0.29; subcutaneous fat, 0.20; eye, 0.16; abdominal fat, < 0.08; and brain, <0.05. Johnson et al. [1979] observed that 30.2 percent of the dose 89 days after administration had been excreted in the urine and 12.6 percent in the feces. Analyses of the urine, feces and tissues have suggested that PFOS is not metabolized (Johnson et a., 1984]. The plasma half-life was calculated tobe 7.5 days aftera single oral dose of radiolabeled PFOS (mean dose, 4.2 mg/kg) in solution to three male rats [Johnson and Ober, 1979). `There appears to be significant enterohepatic circulation of POS with both urinary and fecal excretion (Johnson et al., 1979; 1980; 1984]. Tn male rats, cholestyramine administered in the feed decreased the retention of radiolabeled PFOS in liver, plasma, and red blood cells, 3.8, 7.7 and 6.0 fold, respectively, and increased its elimination via feces 9.5 fold after the rats were given intravenous radiolabeled PFOS (mean dose, 3.4 mg/kg) [Johnson et al., 1980; 1984]. There was a lower clearance rate of "Cin the urine compared to control animals because of the increased rate of fecal elimination. Cholestyramine is a bile acid sequestrant that acts by binding bile acids in Page 001076 the intestinal tract. This reduces bile acid resorption and its retum to the liver. Decreased flow of bile acids in the enterohepatic circulation results in increased conversion of hepatic cholesterol into bile acids. This results in adecline in hepatic cholesterol concentration and the stimulation of low density lipoprotein (LDL) receptor synthesis, which subsequently produces a decline in serum LDL cholesterol levels. Upon acute exposure, PFOS was moderately toxic by oral administration (Gabriel, 1976; Dean et al., 1978; Rusch and Rinehart, 1979], but not dermal [O'Malley and Ebbens, 1980]. There have been two acute oral toxicity studies reported (Gabriel, 1976; Dean etal., 1978]. In the more recent study POS was suspended in a 20% acetone/80% com oil mixture and administered orally by gavage levels to 5 male and $ female rats per group at the following dosages: 100, 215, 464 and 1000 mg/kg [Dean et al., 1978). Animals were observed for 14 days. The acute oral LDS0 values (95% confidence limits in parentheses) were male rats, 233 (160 - 339) mg/kg; female rats 271 (200 -369) mg/kg: combined male and female rats; 251 (199 - 318) mg/kg. Clinical signs included diarrhea, hypoactivity, decreased limb tone, ataxia, comeal opacity, ptosis, piloerection, prostration and tremors. In the previous study, PFOS was administered in water and the LDS0 in the rat was determined to be 1.25 - 2.50 g/kg (Gabriel, 1976]. Gabriel's results appear to be: inconsistent with subsequent toxicity studies. In an acute inhalation toxicity study [Rusch and Rinehart, 1979), a series of onehour inhalation exposures in rats at exposure concentrations of PFOS at 24.09, 7.05, 6.49, 4.88, 2.86, 1.89and 0.0 mg/L produced 100 percent mortality at the highest level and partial mortality (10 - 80%) at all other PFOS levels. Observations included dyspnea, tremors, convulsions, hypersensitivity, hypoactivity, excessive salivation and lacrimation Page? 001077 and general poor condition. The LCS0 was determined to be 5.2 mg/L (95% Cl = 4.4 6.4 mg/L). PFOS has been shown to be a potent inducer of hepatic peroxisomes and fatty acid beta-oxidation in the rat [Ikeda et al, 1987) and mouse [Sohlenius et al., 1993]. After feeding male rats for two weeks with a powdered chow containing 0.02% PFOS, hepatic catalase, fatty acyl-CoA, camitine acetyl transferase and camitine palmitoyl transferase increased by 1.74, 4.90, 6.84 and 1.69 fold, respectively, compared to control animals [Tkeda et al, 1987). PFOS also induced cytochrome P-450 activity. Male mice administered perfluorooctane sulfonic acid at a concentration of 0.05% weight/weight in the diet for S days resulted in weight loss and increased peroxisomal fatty acid betaoxidation, peroxisomal catalase activity, Q-hydroxylation of lauric acid, cytosolic epoxide hydrolase activity and cytosolic DT-diaphorase activity [Sohlenius et al., 1993]. Haughom and Spydevold [1992] fed 0.02% perfluorooctane sulfonic acid in the dict for 7 - 14 days to male Wistar rats which resulted in increased liver weight, liver triacylglycerol, liver free cholesterol and decreased liver cholesterol ester as well as decreased serum cholesterol and triacylglycerol levels. There was reduced cholesterol synthesis from acetate, pyruvate and hydroxymethyl glutarate but no reduction in synthesis from mevalonic acid in the hepatocytes from the treated rats. The activity of liver hydroxymethyl glutaric acid-Co-A reductase (HMG-CoA) and acyl-CoA cholesterol acyltransferase (ACAT) was reduced. Haughom and Spydevold [1992] suggested that the hypolipidemic effect of perfluorooctane sulfonic acid may be due to downregulation of HMG-CoA reductase and ACAT with enhanced fatty acid oxidation in the liver. This would subsequently reduce very low density lipoprotein (VLDL) production by the liver. roge 001078 Recently, Nabbefeld et al. [1998] tested the hypothesis that PFOS and other fluorocompounds may act as peroxisome proliferators by displacing fatty acids from liver fatty acid binding protein (L-FABP). 10 uM PFOS caused a66 percent reduction of the fluorescently labeled fatty acid analog 11-(S-dimethylaminonapthalenesulfphony))- undecanoic acid from L-FABP in vitro. Comparable results were observed for bovine serum albumin. These findings demonsirated that PFOS has a high affinity for fatty acid carrie proteins and can displace the endogenous ligand. Results from three subchronic studies have been reported [Goldenthal et al., 19784; 1978b; 1979]. PFOS was fed in the diet of Charles River CD rats at0 (control), 30, 100, 300, 1,000 and 3,000 ppm fo9r0 days [Goldenthal et al., 19784]. At the 300, 1,000 and 3,000 ppm dosage level, all rat diedpriorto scheduled termination. Toxicity signs included emaciation, convulsions, ocular and anogenital discharges, increased sensitivity to extemal stimuli and reduced motor activity. Histopathology showed compound-related lesions which included hepatic hypertrophy and necrosis, thymic and splenic follicular atrophy, bone marrow hypocellulaity and atrophy of mesenteric lymph nodes, small intestinal vill and skeletal muscle. Among the 100 ppm dose group there was weight loss, elevated plasma creatinine phosphokinase, alkaline phosphatase, blood glucose and blood urea nitrogen, decreased hemoglobin, hematocrit, erythrocyte and leukocyte counts, hepatic enlargement and necrosis, and stomach discoloration and hemorrhage. Among the 30 ppm dose group there was weight loss, clevated plasma glutamate-pyruvate transaminase and plasma glutamate oxalacetate transaminase, and liver discoloration. Page9 001079 Ina subchronic (90 day) study [Goldenthal et al, 1979], two male and two female hesus monkeys per group received 0 (control), 10, 30, 100 and 300 mg/kg/day of PFOS by oral gavage. ~All animals (except controls) died within 20 days and timing was related to dosage. Monkeys treated with 300 mg/kg/day died between the second and fourth day. Monkeys treated with 100 mg/kg/day died between the 3 and 5 day. Monkeys treated at 30 mg/kg/day died between the 7" and 10" day and those treated at 10 mg/kg/day died between the 1 and 20 day of the study. Signs of toxicity at each dosage level were comparable and included anorexia, diarrhea, decreased activity, emesis, weight loss, marked weakness, prostration, and general body tremors. There were no consistent histopathologic changes with exposure. Adrenal changes, including congestion, hemorrhage and lipid depletion of the adrenal cortex, were observed in all dose groups. An additional subchronic rhesus monkey study was subsequently initiated at much lower dosages [Goldenthal, 1978b). PFOS was administered by oral gavage to two male and two female monkeys at dosages of 0, 0.5,1.5 or 4.5 mg/kg/day for 90 days. Animals treated at the 4.5 mg/kg/day dosage level died or were sacrificed in extremis by the seventh week with signs of gastrointestinal toxicity comparable to those observed in the previous rhesus monkey study by Goldenthal et al. [1978al. Also, in the 4.5 mg/kg/day dose group, mean serum cholesterol levels declined from 183 mg/100 mi 0 99 within 30 days. SGOT increased from 36 0 95 wl and alkaline phosphatase decreased from 1088 to 590 ul. SGPT remained unchanged. Histopathology showed compound-related `marked diffuse lipid depletion of the adrenals as well a diffuse atrophy of the pancreatic exocrine cells. Animals inthe 0.5 mg/kg/day and 1.5 mg/kg/day dosage groups survived 0 the end of the study. Occasional diarrhea, anorexia and emesis were observed. There Page 10 001080 was a decrease in serum alkaline phosphatase and inorganic phosphate in the 1.5 mg/kg/day group and a slight decrease in alkaline phosphatase in the 0.5 mg/kg/day group at the end of 90 days. Histopathology was unremarkable in both dosage groups. Ao observable adverse effect level (NOAEL) was not identified from any of the above three subchronic (90 day) studies. The results from these three subchronic studies suggest there may be a potential for cumulative toxicity over time with the primary toxic effect related to metabolic wasting. This may be due to an effect on peroxisome proliferation, fatty acid metabolism, membrane function, protein synthesis and/or `mitochondrial bioenergetics. To date, there are no data regarding the chronic toxicity and carcinogenicity of PFOS. PFOS was not observed to be mutagenic in several Salmonella typhimurium strains with or without metabolic activation [Jagannath and Brusic, 1978]. PFOS was negative in an in vivo mouse bone marrow micronucleus assay [Murli, 1996]. `There have been two teratology studies conducted with PFOS. Oral administration, via com oil, of PFOS at doses of 0, 1,5 and 10 mg/kg/day to pregnant rats during days 6 - 15 of gestation resulted in fetuses with what was initiallyreportedas teratogenic changes in the eye. (Gortner et al., 1980]. These fetal lens abnormalities were subsequently interpreted to be artifacts of the tissue sectioning process. Matemal body weights in the high dose group were significantly reduced but no significant treatment-related teratogenic or embryotoxic effects were reported. In the second teratology study, PFOS was administered in com oil by oral gavage to groups of 25 pregnant rats on days 6 - 15 of gestation at doses of 0, 1,5 and 10 mg/kg/day [Wetzel et al., 1983]. Matemal body weights and food consumption at 5 and 10 mg/kg/day were Page 11 001081 significantly reduced comparedto the control animals. Two female rats in the high dose. group died before day 20. Clinical signs in surviving dams included hunching, thinness, alopecia, rough haircoat and anorexia. Treatment-related effects, primarily occurring in the high dose group, included increase resorptions and fetal death, decreased fetal body weight, delayed skeletal ossification, cleft palate, subcutaneous edema and eryptorchidism, During the past 15 to 20 years there have been several endeavors designed to ascertain the health and exposure status of workers involved with fluorochemical production at the company's Decatur, Alabama and Antwerp, Belgium plants. Medical surveillance has been routinely conducted of fluorochemical production workers at both plants. Medical surveillance activities analyzed for total serum organic fluorine levels until themid-1990's when serum PFOS determination, quantifiable by liquid chromatography mass spectrometry, became incorporated in the biennial medical surveillance examinations. However, we are aware of one occasion in 1979 where the serumof 5 Decatur employees was measured for PFOS by electron capture gas chromatograph and microwave plasma detection methods [Central Analytical Laboratory, 1979). Total serum organic fluorine levels for these five employees were 10.1, 5.7, 9.4, 11.8 and 4.1 ppm. The percent of PFOS found was 60%, 70%, 80%, 55% and 65% of the total serum organic fluorine levels, respectively. In 1981, selected clinical chemistries and hematology values of Decatur employees in the chemical plant were compared to those results of employees in the adjacent 3M film plant (Roach, 1982; `Schuman, 1982]. There were no significant correlation coefficients between total serum organic fluorine and gamma glutamyl transferase, serum glutamic oxaloacetic page 12 001082 transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, cholesterol, hemoglobin or red blood counts. However, this analysis was limited in scope (no dose response analysis), did not analyze specifically for PFOS, and did not account for several potential confounding factors. Another research initiative into the health status of Decatur employees wasaretrospective cohort mortality study (1961 - 1991) conducted of former and current employees who had worked at least one year at the Decatur plant [Mandel and Johnson, 1995). Vital status was determined for 99.7% of the 1,957 cohort `members who had worked in the chemical and film plants. A total of 74 deaths were identified compared to 117.7 expected (U.S. rates). Among male employees who had worked only in the Decatur chemical plant, there were 32 deaths compared to 44.1 expected. There were no specific causes of death that had significantly elevated standardized mortality ratios. Because of its more recent construction in the 1970's, there has not been a retrospective cohort mortality study conducted of employees at the Antwerp plant. `The purpose of this report is to provide an aggregate analysis of the hematological, clinical chemistry and hormonal parameters, as measured in the medical surveillance examinations of Antwerp and Decatur employees in two separate time. periods, in relation to the workers" serum PFOS levels. Although female employees also participated in these medical surveillance examinations, their actual numbers were too few to provide meaningful statistical analysis. METHODS PFOS Production Page 13 001083 PFOS production began in Antwerp in 1976 and in Decatur in 1961. In general, perfluorinated chemicals are produced via an electrochemical process: a solution of organic substrate is electrolyzed in anhydrous hydrogen fluoride ata low voltage (Simons and Bryce, 1954). Basically, the products of this electrolysis cell reaction are highly fluorinated compounds with the end-product defined by the starting material. Products `manufactured at these two plants include: ScotchgardTM brand fiber, leather and carpet protector; Light WaterTM brand aqueous film forming foam (AFF); ScotchbanTM paper treatment; Kel-FTM brand plastic and FluorelTM brand elastomers. Subject Selection General medical surveillance occurs biennially for employees at both of these. plants. Participation is voluntary with approximately 100 Antwerp and 250 Decatur employees eligible for surveillance. A total of 88 Antwerp employees participated in the medical surveillance examinations in the Spring, 1995 and 90 Decatur employees participated in the Fall, 1994. In the Fall of 1997, a total of 149 employees (Antwerp = 65: Decatu=r 84) participated in medical surveillance examinations. For purposes of brevity, these time periods will be referred to as 1995 and 1997. Altogether, 61 employees participated in both examination years (1995 and 1997). This lower number was due 0 a large tumoverofemployees at both plant locations during 1996-1997. For ach time period the surveillance consisted ofa medical questionnaire, measurement of height, weight and blood pressure, standard clinical chemistry and hematology tests, and determination of serum PFOS levels. Page 14. 001084 In 1995, several hormones were also analyzed for male employees who were judgead priori to have had likely PFOS exposure (ic., those working in or in the immediate vicinity of the PFOS production arca). Of the 88 Antwerp employees, 50 had hormone measurements. Of the 90 Decatur employees, 38 underwent hormone measurements. PFOS Analysis In 1995 the analysis for serum PFOS was conducted by 3M'S Environmental Technology Services in St. Paul, Minnesota. The method used tetrabutylammonium to ion-pair with PFOS in serum. The ion-pairs were then extracted with ethyl acetate. The abstraction product was then analyzed using high performance liquid chromatographythermospray mass spectrometry [Johnson et al, 1996]. In 1997 the serum samples were analyzed by TurbolonSpray liquid chromatography/mass spectrometry using selected ion monitoring in the negative ion mode by Advanced Bioanalytical Services, Inc. [Anderson etal, 1997a; 1997b]. The lower limit of quantitation was 0.1 g/mL for PFOS. Laboratory Analyses For both time periods, the United Laboratory Services (St. Paul, Minnesota) performed the standard hematological and clinical chemistry tests. These included the following hematological tests: hematocrit (percent), hemoglobin (gm/dl), red blood cells (RBC, 1000/mm'), white blood cells (WBC, 1000/ mm') and platelet count (1000/ mm'); and the following clinical chemistry tests: alkaline phosphatase (IU/L), gamma glutamy transferase (GGT. IU/L), aspartate aminotransferase (AST, IU/L) formerly Page 15 001085 known as serum glutamic oxaloacetic acid (SGOT), alanine aminotransferase (ALT, IU/L) formerly known as serum glutamic oxaloacetic transaminase (SGPT), total and direct bilirubin (mg/d), blood urea nitrogen (BUN, mg/dl), serum creatinine (mg/dl), glucose (mg/dl), cholesterol (mg/dl), high density cholesterol (HDL, mg/dl) and triglycerides (mg/dl). Low density lipoprotein (mg/dl) was calculated as the following: LDL = [cholesterol - HDL - (tryglycerides/s)]. Eleven hormones were assayed in 1995: cortisol, dihydroepiandrosterone sulfate (DHEAS), estradiol, follicle stimulating hormone (FSH), 17 alphahydroxyprogesterone (17-HP), free testosterone, total testosterone, luteinizing hormone (LH), prolactin, thyroid stimulating hormone (TSH) and sex hormone binding globulin (SHBG). All but SHBG (Endocrine Science Reference Laboratory, Tarzana, CA) were analyzed at the University of Minnesota's Endocrinology Laboratory. Cortisol was assayed using a fluorescence polarization immunoassay (Abbott TDx). Radioimmunoassays (RIA) were used for DHEAS (Pantex), estradiol (modified Pantex), 17-HP (modified CIS) and total testosterone (Diagnostic Product Corp. Coat-A Count). Free testosterone was determined using equilibrium dialysis. LH, FSH and prolactin were assayed using a microparticle enzyme immunoassay (Abbott Imx). TSH `was determined using a chemiluminescence immunometric assay (Nichols). SHBG was. assessed via a radioimmunoassay after chromatographic sample purification (Endocrine Science Reference Laboratory). Bound testosterone was calculated as total testosterone less free testosterone. Data Analysis Page 16 001086 Descriptive simple and stratified analyses, Pearson correlation coefficients, ANOVA and ordinary multivariable regression were used to evaluate associations between PFOS and cach hematological and clinical chemistry test and hormonal assay. Age, body mass index, current alcohol consumption (drinks per day) and cigarette use (cigarettes smoked per day) were potential confounding factors that were considered in the analyses. For stratified analyses, employees were divided into four PFOS categories: 0-1ppm, 1 - <3 ppm, 3 - <6 ppm and > 6 ppm in order to determineifan effect existed at the highest serum PFOS levels. Other categorical cutoff points were also used which provided similar results. For multivariable regression analyses, PFOS and the potential confounders of age, body mass index (BMD), alcohol use and cigarette use were examined as continuous explanatory variables in the models. Multivariable regression models were fitted with PFOS analyzed as a continuous variable using linearas well as non-linear transformations (quadratic, square, square root and inverse) in order to maximize the possibility of finding associations between PFOS and the dependent variableof interest. Linear and nonlinear relationships were examined by residual diagnostics using studentized and Cook's distance values. Natural log transformations of the dependent variables were performed, when necessary, to normalize variables and to enhance model fit. Traditional stepwise selection procedures were also employed (selection in and out of model was set atp = 0.1) as well as taking into account other covariants thatmaybe on the biologic pathway of effect [Greenland 1989). We did not examine changes in measured PFOS between the two time periods because the estimated half-life of PFOS is atleast two years. Study results were analyzed using the SAS System [1990]. Page 17 001087 Analyses are presented by plant, year and the three major groups of participants: all employees who participated in each year (1995: N = 178; 1997: N = 149); only those employees (N = 61) who participated in both years; and only those employees (N = 88) who participated in the hormone measurements in 1995. RESULTS `The distribution of employees, by serum PFOS exposure categorization, is presented in Table 1. Whereas 20 percent of the Decatur employees had exposures at > 3 ppm for both years, this proportion in Antwerp went from 25 percent in 1995 to 13 percent in 1997. For both years 95 percent of the measured serum PFOS levels were below 6 ppm. There were no PFOS measurements > 6 ppm in Antwerp in 1997. `The overall mean values of PFOS, demographic, serum chemistry and hematological parameters for both locations, as well as each location separately, are presented in Tables 2 and 3, respectively. In particular, the Antwerp male employee population was significantly younger than Decatur, had lower body mass indices and higher self-reported daily consumption of alcohol. In addition, theirclinical profiles were also different for several tests. The Antwerp employees had lower mean alkaline phosphatase, creatinine, glucose and triglyceride values and higher total bilirubin, HDL and hematocrit values. Presented inTable 4 are the Pearson correlation coefficients between PFOS and the selected parametersofinterest by both locations combined, each location separately, and by year ofexamination. In 1995, variables that were significantly (p <.05) correlated with PFOS for both locations combined included total bilirubin, white blood Page I8 001088 cells and platelets. Although creatinine was not significantly correlated when both locations were examined, it was negatively correlated with PFOS in Antwerp but positively correlated in Decatur. In 1997, variables that were significantly correlated with PFOS for both locations combined were BMI ALT, direct bilirubin, cholesterol, LDL and hematocrit. In addition, GGT and triglycerides were significantly positively correlated with PFOS among only Antwerp employees. Provided in Table 5 are the mean, median, standard deviation and range of the covariates and the clinical chemistries and hematological parameters by four levels of PFOS categorization (0-< I, 1 -<3,3 <6 an>d6 ppm) for both years. Several observations are noteworthy. First, the mean for the > 6 ppm PFOS category was one order of magnitude higher than the lowest PFOS category (0 - < I ppm) for both years. Also, the means of the four PFOS categories were significantly different from each other. Second, the youngest employees had the lowest serum levels of PFOS. Third, there was only one variable, total bilirubin, which had significant (p < 05) Ftests for differences in `means in both years of analysis. Besides total bilirubin, the onlyother variable in which the mean of the higher levels of PFOS exposure (3 - < 6 ppm or > 6 ppm) was significantly different from the lowest category level of PFOS exposure (0- < 1 ppm) was for WBC's in 1995. This was not observed in 1997. The lowest mean platelet count was observed at the highest PFOS exposure category in both years although the mean platelet counts by PFOS categories were not significantly different from each other. Provided in the next two tables are the mean, median, standard deviation and range of the covariates and the clinical chemistries and hematological parameters by the four levels of PFOS categorization for each plant for 1995 (Table 6) and 1997 (Table 7). Page 19 001089 In 1995 (Table 6) in Antwerp only, alcohol consumption was associated with higher PFOS levels. Mean serum creatinine levels declined in Antwerp but increased in Decatur employees. Antwerp employees in the 3 - < 6 ppm PFOS category smoked more cigarettes and had higher WBC levels. In 1997, Antwerp employees in the lowest PFOS exposure category were significantly younger than their counterparts. Antwerp employees in the higher PFOS category levels had higher mean alcohol consumption levels. Mean cholesterol, LDL and triglyceride levels trended upwards by PFOS exposure categories for Antwerp employees. Linear and nonlinear relationships between PFOS and the dependent variables of interest, taking into account the potential confounding affects of age, BMI, alcohol and cigarettes, resulted in numerous analyses. For purposes of brevity, linear regression models are presented in Table 8 which show the effect that the parameter of interest, PFOS, has on the various dependent variables, adjusted for age, body mass index, alcohol and cigarette use. These covariates were analyzed as continuous variables. In the case of serum creatinine and total bilirubin, a quadratic (PFOS + PFOS?) analysis provided the best statistical model of the data adjusted for the four potential confounders. The natural log transformation of total bilirubin, GGT and glucose provided the best fit for these response variables. PFOS was significantly associated (p <.10) in both years for only one clinical parameter: total bilirubin. PFOS was associated in one of the two years for the following variables: direct bilirubin, creatinine, cholesterol, LDL, HDL, hematocrit, hemoglobin and platelet count `Those variables that were observed to be associated in at least one year in the regression models in Table are separated by plant location and year in Table 9. After Page 20 601090 separate analyses by employee population, only two variables, total bilirubin and HDL, remained significantly (negatively) associated with PFOS for at least one plant location for both time periods. Total bilirubin showed a significant negative association with PFOS (quadratic relation) for employees at the Decatur plant in both years. There were no significant associations among the Antwerp population between PFOS and total bilirubin. HDL was significantly negatively associated with PFOS in Antwerp in both 1995 and 1997 but was not significantly associated with PFOS in Decatur in either year. As for inconsistent associations observed in Table 8, direct bilirubin was not significantly associated with PFOS in either plant location (Table 9). The quadratic association for PFOS with creatinine was observed in Antwerp in 1995 and Decatur in 1997 but not in Antwerp in 1997 or Decatur in 1995. Cholesterol (and LDL) was observed to be positively associated with PFOS only in Decatur in 1997. Hematocrit and hemoglobin were associated with PFOS only in Decatur in 1997. Platelet counts were observed to be significantly negatively associated with PFOS only in Decatur in 1995. Traditional stepwise regression modeling techniques were also used as well as testing models with variables that would be considered on the biological pathway of effect for any dependent variable. The associations (or lack thereof) from these analyses were similar to what has been presented in Tables 8 and 9. For purposes of brevity these analyses are not shown. To further understand the association between total bilirubin and PFOS, scatter plots are presented for both time periods and by location in Appendix A. In addition, unconjugated bilirubin was also calculated (total bilirubin -direct) and these scatter plots are presented in Appendix B. Table 10 is a summary of these scatter plots from both Page 21 001091 Appendices. The strongest associations appeared to be quadratic in nature primarily for the Decatur location and the percent of variability explained ranged between 3 (1995 data) and 7 percent (1997 data). The linear component of the quadratic was negative in direction. The upward trend appeared to occur around 6 ppm PFOS where the data are: sparse. These simple linear and quadratic models were not influenced byany one employee according to residual diagnostics. To further understand the possible association between HDL and PFOS, scatter plots are presented for both times and by location in Appendix C. Both locations combined resulted in significant negative linear and nonlinear (quadratic) associations in 1995 although the percent of variability explained in these models ranged between 3 and 5 percent. No significant associations were observed for each plant location in 1995. `There were no significant negative associations between HDL and PFOS in 1997 for cither the combined locationsoreach separate plant ste. Provided in Tables 11 through 14 are the analyses restricted to the 61 employees who participated in surveillance in both years. Table 11 provides the mean values for ach parameter for the employees who participated in both exams compared to those who participated in only one of the two years. Overall, there were few differences. The mean age of the 61 employees was lower than that of the 1995 employees who didn't participate in 1997. Conversely, the mean age of the 61 employees was higher than that of the 1997 employees who didn't participate in 1995. Cholesterol and LDL were significantly higher in the 61 participants in 1997. Tables 12 and 13 present the mean values by plant location for 1995 and 1997, respectively. Of these 61 employees, 27 were from Antwerp and 34 from Decatur. OF noteworthy importance are the differences Page 22 001092 between the 27 Antwerp employees and their fellow employees in 1997 (Table 13). The 27 Antwerp employees had significantly higher mean PFOS exposures, were significantly older, had greater BMI's and higher cholesterol values. Multivariable: regression analyses for the 61 employees are presented in Table 14. The only significant association with PFOS appeared to be with serum creatinine (quadratic) in 1995. Regardless of plant location, mean PFOS levels were higher for those employees who were selected for hormone measurements in 1995 (Table 15). This was expected as these employees were selected with the apriori belief that their serum measurements. would be higher due to their workplace experience. For example, of the 42 employees in 1995 whose serum PFOS levels were > 3 ppm, 76% had hormone measurements. Presented in Table 16are the mean values for PFOS, demographic, serum chemistries and hematology for those employees who had hormone measurements comparetdo those employees who did not in 1995. Those employees who had hormone `measurements were younger, higher users of alcohol (Antwerp only) and cigarettes (both locations). and had lower serum creatinine (Antwerp only) and higher WBC levels (both locations). The latter observation is confounded by cigarette smoking as among nonsmokers, those selected for hormone measurements had a mean WBC of 6.24 compared 106.03 for non-selected employees (p =.36). Among smokers, those selected had a mean `WBC of 8.69 compared to 8.06 for non-selected employees (p = 23). ~ All other clinical parameters were comparable, by PFOS exposure categories, between subjects who had hormone measurements and those who did not in 1995 (Tables 17 and 18). `The Pearson correlation coefficients between PFOS and the hormones tested `among the 88 employees were the following: cortisol (07), DHEAS (-.13), estradiol Page 23 001093 (09), FSH (06), 17-hydroxyprogesterone (-04), LH (03), prolactin (06), SHBG (11), free testosterone (-.06), bound testosterone (.06), TSH (01). None were statistically significant. Presented in Table 19 are the mean, median, standard deviation and range of the. various hormones by the four PFOS categories: 0- <I ppm, 1 - <3 ppm, 3 - <6 ppm and 26 ppm. Several observations are noteworthy. First, the mean age of the lowest PFOS exposure category was 10 years less than that of the highest exposure category. Therefore it was not unexpected to observe that the mean DHEAS, 17-HP, free testosterone and bound testosterone levels of this lowest exposure category were greater than the means of the higher PFOS exposure categorizations. Adjusting for the differences in age (as well as the other three potential confounders) in the regression models (Table 20) resulted in no significant associations between PFOS and the hormones analyzed, except for estradiol. With estradiol, a quadratic model provided the best fit of the data and both PFOS terms were significant. Upon residual diagnostics it was determined tht this estradiol model was influenced by one specific employee (employee A). The influence of employee A is best seen in Figures 1 and 2 which are simple scatter plots of both the linear and quadratic fits of estradiol and PFOS, with and without employee A, respectively. Employee A had a 12.83 ppm serum level of PFOS which was the highest value recorded in 1995. His estradiol value was 92 pg/dl (see upper right hand comer of Figure 1). Employee's A estradiol value was also influenced by the fact that his body mass index was 33 kg/m'. Exclusion of this employee resulted in a nonsignificant quadratic equation. The variability (R?) of the data explained went from 7.6 percent to 2.1 percent upon exclusion ofthis employee. The slope of the linear equation changed from Page 24 001094 positive to negative although it was nonsignificant in both Figures 1 and 2. Finally, it should be noted that the estradiol models in Table 20, with and without employee A, did predict the known positive assocation between estradiol and body mass index. DISCUSSION We conducted two cross-sectional analyses of surveillance data to examine the associations between serum PFOS levels and several hematological, clinical chemistry and hormonal parameters in male fluorochemical production employees. For both years, 95 percent of the measured serum PFOS levels were below 6 ppm. Because the Antwerp and Decatur employees were dissimilar by age, body mass indices and self-reported alcohol use, we conducted combined as well as separate analyses by plant location. These three demographic differences likely explainwhy the Antwerp employees had lower mean serum levels of alkaline phosphatase, HDL, triglycerides and blood glucose [Davern and Scharschmidt, 1993; Lewis, 1994; Friedman, 1998; Fu, 1998; Wolf, 1998]. In the present study, alkaline phosphatase, GGT, AST and ALT values were not significantly associated with the measured serum PFOS levels. This was an apriori question due to the fact that PFOS: 1) is a peroxisome proliferator in the rat (Ikeda et al., 1987; Sohlenius et al, 1993]; 2) resulted in slight to marked increases in plasma `glutamic oxalacetic and pryuvic transaminase levels in a 90 day study of rats fed diets `which contained PFOS at 100 ppm along with hypertrophy and liver necrosis observed at histopathology [Goldenthal, 19784}; and 3) increased SGOT and decreased alkaline: phosphatase levels in monkeys after administration, by oral gavage, for 30 days of doses. of 4.5 mg/kg/day of PFOS [Goldenthal, 1978b]. On the other hand, SGPT values rogaas 001095 remained constant and no histopathologic abnormalities were noted in the livers of these. `monkeys which died by the 7" week of the study. No significant liver enzymatic or histopathology changes occurred in monkeys in the 0.5 and 1.5 mg/kg/day dose groups. We did observe a quadratic association with total bilirubin among only the Decatur employees. We do not suspect this is a biological association because the bilirubin levels were within the normal reference range. Also, the percent variability explained of total bilirubin by PFOS in the regression models was low. The Antwerp employees' total bilirubin levels weresignificantlyhigher than the Decatur employees'levels. We offer several possible explanations for this observation. First, we suspect there may be a greater prevalence of Gilberts syndrome [Lidofsky and Scharschmidt, 1993; Friedman, 1998] among the Antwerp employees. In 1995, 15 (17%) Antwerp employees had total bilirubin values > 1.2 mg/dl compared to 3 (3%) Decatur employees' levels. In 1997, there were 9 (15%) Antwerp and 2 (29%) Decatur employees with total bilirubin values > 1.2 mg/dl. However, there was not a `concomitant decline in bilirubin conjugation (i.., direct bilirubin levels) as might be expected among individuals diagnosed with Gilbert's syndrome. Nevertheless, exclusion of these possible Gilbert's syndrome employees still resulted in higher mean total bilirubin values among the Antwerp employees in both years. Secondly, there were four Antwerp employees who self-reported hepatitis A histories and one employee selfreported a history of Hepatitis B. Fish and shellfish consumption is likely much greater in Antwerp than Decatur due to its vicinity near the North Atlantic. Third, bilirubin is a tetrapyrrole that is an end-product of heme degradation [Lidofsky and Scharschmidt, 1993]. Bilirubin levels may be increased due to disorders of bilirubin metabolism, liver Page 26 001096 disease and obstruction of the bile ducts. Other hematological and clinical chemistry results did not suggest these conditions existed among the Decatur employees. Fourth, post-collection procedures may result in error. Total bilirubin determination may be falsely depressedif hemolysis is present because of increased absorbence in the blank [Kaplan and Pesce, 1984). Bilirubin is also sensitive to and destroyed by light and heat. We are uncertain whether these factors could have contributed to the lower total bilirubin levels in the Decatur samples in both years. Finally, the linear component of the `quadratic association observed among Decatur employees is negative in direction in relation with their measured PFOS levels. That is, total bilirubin levels declined with increasing PFOS levels. We would expect a positive association if PFOS impaired bilirubin conjugation. The trend upwards in the quadratic appears to occur at levels 6 ppm and higher where the data are sparse. We conclude that the association observed among only the Decatur employees is unlikely to be related to serum levels of PFOS. We did observe a positive association between serum PFOS and serum cholesterol levels in the 1997 time period forDecatur employees. This result is unlikely to have a biological explanation as PFO is a known peroxisome proliferator in the rat and was shown to have hypolipidemic properties in thesus monkeys (Ikeda et al. 1987; Sohlenius etal., 1993; Goldenthal 1978b; 1979]. Rhesus monkeys fed PFOSat 4.5 mg/kg in their chow had serum cholesterol values reduced from 183 mg/L to 99 mg/L within 30 days. Rhesus monkeys fed 1.5 mg/kg in the chow had cholesterol levels reduced from 195 mg/kg to 111 mg/kg within 90 days [Goldenthal 1978b). As for HDL, although the multivariable analyses were suggestiveof a negative association between HDL and PFOS Page 27 001097 in Antwerp (but not Decatur), the scatter plots presented in Appendix C do not support the notion of a biological association between PFOS and HDL. It should be noted that total organic fluorine levels, primarily consisting of perfluorooctanoic acid (PFOA, C:FisCOO'), aseven carbon perfluorinated carboxylic acid, were reported to reduce the effect that alcohol has on HDL levels among higher exposed male PFOA production workers in Cottage Grove, Minnesota [Gilliland and Mandel, 1995). However, this finding was not observed in subsequent analyses of these employees (Olsen et al, unpublished findings). This observation by Gilliland and Mandel was testable in the present study as both Antwerp and Decatur employees had measurable quantities of PFOA. We did not observe a significant negative modulation of the effect of alcohol consumption on HDL levels among Antwerp and Decatur employees with higher serum PFOA levels although their serum levels were approximately 3 to 5fold less, on average, than that reported in Cottage Grove employees [Olsen et al, 1998], `The Antwerp and Decatur employees were exposed to PFOA, not in its actual production, but rather in its use as a surfactant in the production of fluoropolymers. In 1995 the mean serum PFOA level among the Antwerp and Decatur employees combined was 1.46 ppm (rang0e - 13.20 ppm) and in 1997 the mean serum level was 1.57 ppm (range 0.1 11.10). Stratified by plant location, the 1995 and 1997 mean serum PFOA levels were 1.19 and 1.78 ppm in the Antwerp employees and 1.72 and 1.40 ppm in the Decatur employees, respectively. `The multivariable regression models showed a negative association between PFOS and platelet counts at PFOS levels above 6 ppm in 1995 and this trend was also apparent, although to a lesser extent, in 1997. Nevertheless, platelet levels were well Page 28 001098 within the normal reference range in both time periods. This association is not supported by a90 day subchronic toxicity study which showed no decline in platelet counts for monkeys fed 0.5, 1.5 or 4.5 mg/kg for up to 90 days [Goldenthal, 1978b]. Mean platelet counts among the 1.5 mg/kg/day and 0.5 mg/kg/day dose groups were 226 and 231 (10%cmm) compared to 218 in the control group [Goldenthal, 1978b). There were no platelet counts reported in the 90 day rat study although at the end of3 months of study there were slight to moderate decreases in hemoglobin, hematocrit and erythrocyte counts observed for male and female rats in the 100 ppm dose group [Goldenthal, 19782). No consistent associations were observed between PFOS and hemoglobin, hematocrit or RBC values in the present epidemiologic investigation. In a prior subchronic rhesus monkey study that was aborted early due to all animals died by the 20" day, mean platelet counts were 203, 219, 136, 172 and 185 for the 300 mg/kg/day, 100 mg/kg/day, 30 `mg/kg/day, 10 mg/kg/day and control groups, respectively [Goldenthal, 1979]. After controlling for age, a confounder for male testosterone hormone levels [Dali etal., 1981; Griffin and Wilson, 1994], we observed no significant associations with serum PFOS measurements. We did observe a quadratic association between estradiol and PFOS. Upon further examination, this finding was influenced by one particular employee who had the highest PFOS level but was confounded by the individual's large body mass index. Exclusion of this employee resulted in nonsignificant findings. Thus, any interpretation with estradiol is difficult because of the influence this one employee has on the statistical analyses. It should be noted that perfluorooctanoic acid (PFOA), at approximately 50- 100 ppm levels in serum, enhances the aromatase conversion of testosterone to estradiol in the Page 20 001099 rat [Cook et al., 1992; Biegel etal., 1995]. However, PFOA production workers in Cottage Grove with serum levels up 10 30 ppm appeared not to have altered serum estradiol levels [Olsen et al, 1998]. Again, like HDL, this was a testable hypothesis among the Antwerp and Decatur employees although their serum PFOA levels were lower than Cottage Grove employees. We did not observe any significant positive. association between estradiol and serum PFOA levels in these Antwerp and Decatur employees. Several methodological issues should be considered in evaluating the results from this study. First, the cross-sectional design does not allow fora direct analysis of the temporality of an association. Second, the voluntary participation rates in medical surveillance were not ideal as among eligible employees we had 88 and 65 percent participation in Antwerp for 1995 and 1997, respectively, but only 35t0 40 percent in Decatur for both years. Third, given the suspected long half-life of PFOS (at least two years), it maybe conceivable that there may be some biological accommodation to the effects of PFOS which would minimize the possibilityoffinding an association. Fourth, itis known in laboratory animals that PFOS concentrates primarily in the liver. Serum `measurements of PFOS may not adequately reflect body burden. Fifth, the two crosssectional analyses cannot be viewed as independent populations as 61 employees were studied in both years. This was due, in part, to a large moverof employees at both plants between examinations. Sixth, there could be measurement error in important confounding variables. Analysis of the data of the 61 subjects who participated in both `years showed that there was excellent correlation for the confounding factors of BMI (r = 92, = 0001), self-reported aspects of alcohol consumption (r = .88, p = 0001) and te 001100 cigarette smoking (r= 79, p = 0001). As expected, these 61 employees" serum PFOS levels for the two years werehighly correlated (r = 92, p= 0001). Seventh, the quality of medical surveillance data, prior to its use for studying an a priori hypothesis, can often be evaluated by whether known positive associations are observed. In this regard, we observed various expected associations including cigarette smoking and elevated white blood cell counts and large body mass indices associated with elevated liver transaminase levels [Olsen ct al, 1991; Bums et al., 1997). Finally, the pulsatile nature of some of the hormones studied (e.g, FSH, LH, testosterone) has resulted in prior recommendations that mean hormone measurements should be the result of pooled blood from multiple. samples taken at short intervals [Goldzieher et al., 1976). In our study multiple samples were not feasible because of the low probability of employees voluntarily giving three serum samples over a 45 -60 minute period of time. In summary, we conducted two cross-sectional analyses and did not observe: consistent associations by plant locationortime for several hematological parameters, serum chemistries and reproductive hormones with measured serum PFOS levels in male. fluorochemical production employees. Ninety-five percent of the employees had serum PFOS levels below 6 ppm. Our findings suggest that, among these Antwerp and Decatur male fluorochemical production employees, significant hematological, clinical chemistry `and hormonal abnormalities were not associated with serum PFOS concentrations less than 6 ppm. Any inferences derived from the few employees with serum PFOS levels > 6 ppm would be tenuous, at best. Limitations of this study include ts cross-sectional design, the voluntary participation rates, the few subjects exposed at the highest levels, Page 31 001101 and the lower levels of serum PFOS measured among these employees compared to those that caused effects in two speciesoflaboratory animals Page 32 001102 Acknowledgements "The authors gratefully acknowledge the assistance of Michele Burlew, Martha McGough, Jane Quarfoth and the helpful comments of Drs. John Butenhoff, Marvin Case and Andrew Seacat. Poge33 001103 References Anderson DJ, Mulvana DE (1997). 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An epidemiologic investigation of reproductive hormones in men with occupational exposure. to perfluorooctanoic acid. J Occup Env Med (in press). O'Malley KD, Ebbens KL (1980). Twenty-eight day percutaneous absorption study with FC-95 in albino rabbits. Expt No. 0979AB0632, Riker Laboratories, Inc., St. Paul, MN. Roach DE (1982). Fluorochemical Control Study. 3M unpublished report. May 25, 1982. Rusch GM, Rinehart WE (1979). An acute inhalation toxicity study ofT-2306CoC in the rat. Bioldynamics, Inc. SAS Institute, Inc. (1990). SAS Users Guide: Statistics. Version 6, SAS Insitute, Inc., Cary, NC. `Schuman LM (1982). Letter to Dr. Frank Ubel (3M Medical Director) concerning Fluorochemical Control Study. April 29, 1982. Sohlenius AK, Eriksson AM, Hogstrom C, Kimland M, DePierre JW (1993). Perfluorooctane sulfonic acid is a potent inducer of peroxisomal fatty acid beta-oxidation and other activities known to be affected by peroxisome proliferators in mouse liver. Pharmacol Toxicol 72:90-93. Wetzel LT, Burdock GA, Durloo RS, Colpean BR (1983). Rat teratology study. Project No. 154-160, Hazelton Laboratories America, Inc., Vienna, VA. `Wolf PL (1991). Liver function. (In) Howanitz JH, Howanitz PJ (eds), Laboratory medicine: test selection and interpretation. New York:Churchill Livingstone Inc., pages 173-190. page 37 001107 TablIe Distributionof EmployeesbyYear,Locationand PFOSExposureLevel(ppm) -- ioSDw P0R-O<STppm 31--<<o3ppppmm =600m N_@AllEmplovees Na)Antwerp N aos s3s 3 2 6 32 2a 332 (00) 8 (00) -- Dw Decatur NE)AllEmployeesNGAnwerp NE)Decatur 9nn6 a 33 w3s 2B as3s 641 as u3 [FaA 25 o6w % 8 1 (00) 6 (00) Bo a00) 32 &B Tea eonMetin,SundarDoistiond arefScyPametrs, Bo Lots, 995d 1997 wm wes --. wm om v--ee mw ae _a eo te warm wm we wwe coe aw Sw ow Ew me 3 tener saen ms mer wo ee sme wm wm am am we we nw oemme ewne awwme MR CI Sl AE w aa wn wim wm om oe wnee wco aws n0m-8 EO wom ose a Gem 0 0 ow Gee ww om Cot ws me ws we me me wm wows we ow Toe wo me my ews wy we a Wogan 53 ss a9 ome wow Ewe ow ws | Mweev ees 07 940 49 mie ma me sa oTis ew aes wm woe wm mw se ws mma wsw ww WIs.e1s4s6 mew or mabe me weoow se em we a ew wwe om ww wa mo wr wes ms we wo sme os we we wm ss mo mo ww os we oa wes se mse mss swe ae ws awe a mew we we es mews sau 07 910 2 wr ome we wm 800-1010 mes Table 3 Mean Values of POS, Demographic, Serum Chemistry and Hematologic Parameters for Antwerp. and Decatur, 1995 and 1997 Examinations Variable PFOS (ppm) 1995 Data Antwerp Decatur 193 244 997 Data Antwerp Decatur 148 1.96 Age 37 4s Fees " BMI 290 292 235% 300 Cigarettes 47% 79 55 66 Alcohol 1340 02 LI 01 Alk Phosphatase ~~75%** 97 Torx 87 Gor a 48 26+ 36 AST 2* 29 27 2 ALT 44 41 31 34 Total bilirubin 086+ 058 080%* 058 Direct bilirubin ~~ 022 021 ois 012 BUN 170% 148 149 14.1 Creatinine [2 11 09% 10 Glucose reer 92 sree 98 Cholesterol 214 218 206 215 LDL 138 136 134 137 HDL Sauer I 50% a Triglycerides TER 187 pees 192 001111 Table 3 (continued) Variable 1995 Data Antwerp Decatur Hematocrit azo 46 Hemoglobin 154 152 RBC 49 50 MCH 3a 307 MCHC 29% 334 mvc 957% 918 WBC Gave 75 Platelets 24 229 *p<.05 **p<Ol *p<.00l 1997 Data. Antwerp Decatur 46+ 45 154 153 s1 51 305 304 Bae 37 9L6* 90.0 65 64 237% 217 001112 Tabled Comeliion Coeficients Between PFOS and Selected Varisbles by Location andYear of Examination Vari-- able _i ohs Locatib ons _u Anwerp Dect ge ry 10 ot -- Both _Locat_ ions w_Amwo erp_ tD Decatm ur 2 ar "0 Aloha! 25 0 0 ao on BMI 0 1 0s 1s 2 Cigaretes 1 1 08 0 0 -08 BUN "os 0 on on 5 or Creatinine 0 aw 08 2 2 Glucose on nn 0 0 3 Alkaline Phosphatase 06 0 06 o 0 Got o o 0 0 2 06 38 ast aB 0% 0% 002 0" 01 (cToanbtilneuded) Variable Boh Locations1995_ADnawtesr.p Decatur ar "or 03 "os Both Locafons 1A9n9t7weDratpa. Deca 6 m 16 Toul Bilirubin 15 13 or 13 2 or Dirct Bilirubin 03 5 3 Et 13 1 Cholesterol 0 08 2s" a 1 LoL o 0 o 2" 0 " HDL. ar a 2 0 05 00s Trgheedes 04 u "10 10 a -o1 Hematocrit 0 0 0003 6 0s EY Hemoglobin 01 05 0 15 -0s 0 RedBlood Cells -03 -n on 1 -15 -10 88B Men B o a0 ou " 0 Varsble oh Locations _bAmwmerp Mac ED "i wey os 25 WhiteBloodCells 18" a pplaocess yon pIoEnt (cToanblteidn) Dear o Both Locationsp _Anwerp m Deca "0 or "0 "oo on 020 o o 1s 0 as un 06 -n0 S82 Tables Mean, Median, StandfaorrdADnetvwietriponan(dSDDe)coaftMureEmnplsonydeReasnCgoembofinPeFdO,S,1D9e9m5og(rNa=p1h7i8c),nSder1u9m9C7h(eN=m1i4s7t)s and Hematological PrOS* 1995 Duss 1997 Daa pm) Mean Median sp Range Mean Median sp Range 01--<<l3pppomm 326-p<o6mp.pm. o18a2"! 10sm 002s7 a8n17 3297 0281 Fave= 3219, p<0001 PEOS (ppm) w100o-2m01 630006.-52808 017582" 016s4 003267 132%0 a6s6o8 071509 Fualue =367.6,p <.0001 011002-.029879 360095--59330 Asem) 01--<<13ppppmm a3o 3a 98 2215--5680 p3e wau u 22%a..0 3-<6ppm 26pm " 45 "5 77 327.-5556 a2 as2 i5 232..551 Fualue=37.p=02 Fualue=5.1,0p0=2 238BB * opprmo)s 01--<<l3ppppmm 23.6<6mppm 01--<<t3ppppmm 2S6<ppompm 0-1<-1<p3ppmm 236<06mppm 832 BB <4 1995Daa Mean Metin SD o0s8 0016 0079 0172 0030 119 Fualoe=40.p=.009 7275 22683 4s2s 2779 25204 238 Fualie=37,p=.02 2668 0000 1631 10046 0800 2i4 Fralue=45,p= 003 Tales (continued) 1997 Data Range Mean Medion sn Alcohol rinks) 0000.-3366 0033 oott 0038 0000.2690 0120 oott 012s Fualue=18,p=.15 BMI Gm') wwem-eem7z 2m70 26249 5a79 2m6emws0 Wmsy 2297 aa0s Fualue=21,p=.10 Cigars(erday) 0000-420500 8a27 0000 1943 0000-.43000 6a0l 0000 8134 Fualie=15,p=2 Range 00--5403 00.17-108 01811-.441875 216911--33620 00--4400 00--3300 Table (continued) pros 1995 Das --- 1997 Data pm) Men Mein sp Range Mean Medion sn Range 01--<3ppppmm I26cpom m 115654 115s0 W3so 11561s 116400 327 Fualue=1Lp=36 Buy 810--2260 110000-.221300 1144s2 114400 115s0 112500 Fualue=05,p=067 3282 9600--221600 2a9 9900--129000 0-1< -p3ppmm 23-6<p6mppm i1o0 010 0022 019 0192 0032 Fralue=23,p=08 Creatinine 0071--1166 0607-.1162 0099 0099 0190 0099 Fralue=04,p=078 oorr 0067-1132 0ol2 0078-1114 01-S<pippmm 3-2<66ppmpm 2BB o 886 58s 215 45 55 Ir1s Fralue=09,p=44 Glusose 66-01-72600 67-011104s 9 s8s 95 a Fualie=06,p=59 " 6585.-13708 27 7501-997 pros 1995 Dats opm) Mean Median Ta$ bcolnneed) 1997 Daa Range Mean Median Range 0-<S1pppmm 23-6<p6pmpm 5 87 5I 88 Fualue=13.p=28 Alain Prosphasse 27 301.-119518 "& " 12" 9.1136 221 652-.11234 78 I8 21 629-.11210 Fuilie=117,p=32 0-<S1pppmm 32-6<ppompm aa 336 5 3 Fualue=05.p=71 sar 3ES 162-1955 El3 22 1iss 231.8709 E3S 75 Fualie=11,p=34 25 1100--118729 12 B17-o48 Ast 0S-<p1pmpm 7 3.<6ppm 3 F2l Io2 1154-5906 22 22s 2% 5 13 3 z 77 1153.-5563 7 14.43 26pm F3ualue-18,p= 134 . 2%.4 Fualue=05,E6pl=7 3 2-3 23S BB porpoms) 0S-<p1ompm 23-6<p6mppm 01--<S1ppmm 32-6<p6mppm 01--<Spipmm 63-p<6mppm SS8 583 "Table continued) 1995 Dats 1997 Dua Mean Median s Range Mean Median s ar psa "2 201 215.-111883 33 0 1u6n spty aa "7 E0-E59 a5 k51i 11s0 Fualue=10,p=38 Fualue=09,4p=6 ToulBilin o0s66s! 0o6m0 00500 oons--l2s00 oom6r 006600 00201 I0r76 007600 003% 0o50w.1l20 o0s6s 005300 003%1 Falue =44,p=005 Fualoe=29,p=.04 Direc Bilinsin 00221 002200 0000s6 001-0.00400 0o1us2 001100 000047 002201 002200 00004 00120003%0 0o1n0 001100 0000 Fualuc=06,p= 55 Fvalue=35,p=.02 Range 150-80 2u5.s49 003300--213300 ood0d-1o%0 001100--004200 001100--00120 persos oSLdoppwmmn Sem 0v-<otppmm S3oommm 0L-S<tpmom e3 rZmon Rg2o-<tpm Bl i Sm Som 1950s Men Mein adaul a3ans Fanmlie=0.1,p=061 i10 w1w 11 1133 Fualie=02,p 287 i9 is o2n i Firalie=20,p=0i0 i1a 9% 1i2s is1i2 Fale LLpa3s Table' Contin) 199700 sp Range Mew Metin Cholesinl 3I) aoesm 22110968 12o915e7 % em Fual2ie=43,p=006 5 SD mnge 2Bisl1oe0nss Bde oy aoo wvaosu p i i% a1 1 1i in u Buo aie sms 2 550 Fuahpey=37,p=01 is 0 3n 3f1e-6 mo "i iPs i5t MFeole Faleio LLp=31 a% wio u1-e2 wio wBwe Toigerides w wae e aan 115s6 ie m wwmelm swsm asi 5 aw 2F0raie=05.p=67BB wow (PpRmO)S 01-3 -<pt pppmm 23-6<p6pmpm 0L--<Stppopmm 236-p6pmpm 01--<Gtppppmm 23-6<p6pmpm S8s 8 1995 Data Mean Median sp 6a baa 32 aa aa 22 Fralue=24,p=07 115525 115525 0110 1i5s5s 115534 0081 Fulue=22,p=10 1590 4590 0033 50 50 k5o0 0052 Fualie=04, p=.75 Table (continued) Range -Mean 1997Daa Median sD Hematocr 3.5521 aas 66 32 alsa ia"5 "" 23 Fuale=21,p=11 `Hemoglobin 118300--116774 115554 115555 0098 11376--116724 115510 11570 0170 Fralve= 18,p=15 RBC 44330-5577 5510 5512 0033 p4r0e-5)7 5500 k5s0 0033 Fualue=14, p=25 Range 03-.5523 329-a50 Bw3s3. i1a51.-1i6672 44130.5559 4474.05557 (PoRpOmS). 01-<pl pmpm 23-6<p6pmpm 01--<3tppppmm 23-6<06pmpm 01--<Gtppppmm 3-6<p6pmpm 8S2 1995Data Mean Median sp as 09 029 1146 3212 303153 21s Fualue=09,p=45 3312 3312 0016 3al1 33236 0061 Fualue=02,p=90 o9t2 99s 4532 9%4 9%2 9478 Fualue=11, p=35 Ta (bconltinueed) Range EE Mean Mei 22674..334433 2202-.333669 330064 0025 Fralue=06, 1997Daa Median sp 30033 112s 30125 E1X9 p=65 Matic 331197.-334457 3ns6 3366 00s5 331232..334430 3n9s 33s 0057 Fualie=p0=75,6 Mev 5805..110046 9%01 90 a3a6 8851111054 %% o9t1 5527 Fualuc=06, p=59 R-- ange 22667..330318 262.320 33128..33496 33240.-33464 851--19090 8510-.9967 Tae onic) oroms 5950s Mem Mem 0 Ree Men 15970 ve vdmm 1-<3ppm S3-o<o6mppm 6 70! 68 76 69 70 i Falue=43, p=006 wae Bo we 20 36-155 G22 oa41n-133 a ss 69 66 62 61 o 7 Fralue=22, p=09. c VCoemimm maom 2B2l om isFsuate=21, piioo Picts aB0o mmwoeww oomw ==2 0 mmmFae 06, p=i0ia c2I.oMNmaipnmoiss isnifgaamny iiffrn p<< 0055, BBoonfrroonss D(uunnm)n) aanthheemensooff0e-t<e|rpFmOPSROS C3 uMcigms infamy ifn 05, Bonfrons Dunn) c) than he en of1 <3 omccgory. 2 828 2 oL*SarampemlemmSize a 1995Data. Samm 3s f0i 1997Data. 260m 7 s Spee 4 sa 19 38-132 5 15 40-100 s B5o w bsiass $0 ems Table 6 DemoMgeraanp,hiMce,diSaenru(mMeCdh)e,miSsttarnideasradnDdevHieamtaitoonlo(gSiDc)aolfVMaeluaensabnydPRlaanntgeLoocfatPiFoOn,S,1995 PFOS* - Antwerp v: e%DWa Decatur (ppm) Mean MedSD Range MeanMed SD Range 0<1 1 <3 3 <6 26 046! 045 029 000-090PFOS060' 063 019 025-088 169! 150 057 100-290 189' 189 0.58 100-291 396 370 079 300-560 431' 423 082 311-580 F81l7"ue=852041.0, 192 p= 0060110-990 F817"a=6l91104u.5,3ep20= 606-1283 0001 0 <1 36 36 7 2-52 Age 0 39 1 29.58 1<3 3 <6 36 349 25-60 373 7 mes 46 46 7 30-58 "4 47 26.55 26 0Fralue 3=05,p6=71 3a 48 41 7 42-56 Fu=a20l, pu=.e12 0 <1 10 07 10 00-36Alcohol01 00 03 00-09 1<3 3 <6 10 08 09 00-36 20 13 22 00-60 02 00 04 00-20 04 00 09 00-34 26 17 14 LL 07-29 Fualue=29, p=.04 00 00 00 00-0. Fualu=e 11,p=.37 0 <1 241 243 24 179-281BMI301 280 53 228-387 <3 3 <6 243 238 24 231 230 33 196-316 179-314 296 283 62 270 275 34 223-607 191-325 26 237 247 28 206-258 Fualue=09, p=47 307 302 16 294-330 Fualue=11,p=.35 001125 PFOS (opm) 0<1 1 <3 3 <6 26 0<1 1 <3 3 <6 26 0 <1 1<3 3 <6 26 0 <1 <3 3 <6 26 Tabl6e (continued) Antwerp Mean Med SD Range Decatur Mean Med SD Range 30 00 70 4100 70 918 75 90 1000 17 F=3.1,p=.03 0-25Cigarettes14 00 38 0-13 0-23 83 00 129 0-40 0-25 125 00 157 0-40 0-3 0 00 0 0-0 Falue=23,p=.09 Alkaline Phosphatase 7575 16 31-104 7366 19 49-108 96 9 29 47-158 98 95 27 49-191 79 78 20 32-2195 95 9 18 8-124. 741 6-8 Falue =05,p=.69 9% 91 27 73-136 Falue =0.1,p= 98 39 29 2 16-111 GGT SS 41 4 21-155 4830 S8 12-293 46 40 24 2-118 3 34 1 2.55 47 48 16 21-80 3012 3 8.3 5249 20 30-79 Fualue=07, p=.55 Fralue=05,p=.71 6 23 13 15-9 AST 239 19s 2726 14 14-9 23 2 5 13.3 29 27 10 17-85 2726 5 21-37 F3u0al3ue5=09, 6 p=.45 26-37 Mom 7 8.83 Fralue =09,p= 44 001126 Tabl6e (continued) PFOS (ppm) Antwerp. Mean Med SD Range Decatur Mean Med SD Range 0<1 46 a2 18 2-18 ALT ss 41 24 37-18 1 <3 3 <6 4s 40 18 26-12 0 39 6 30-32 47 42 2 18-183 4 2 9 30-5 26 S038 28 29.8 Fualue=07, p=.59 $2053 8 41-59 Fralue =08, p= 49 0 <1 096 080 055 040T-o2t9a0lBilir0u6b5in 060 0.16 040-090 1<3 3 <6 083 080 026 040-130 075 070 030 030-140 057 050 028 020-150 051 050 018 020-100 26 0Fu9a3lue0=9102, 025 p=31 070-120 063 065 010 050-070 Fualue=0.7, p=.54 0 <1 Direct Bilirubin 023 020 006 020-040 020 020 000 020-020 <3 3 <6 022 020 004 020-030 021 020 003 020-030 020 020 006 010-040 020 020 004 020-030 26 020 020 000 020-020 Fralue=07, p=.55 020 020 Fualue=04, 008 p= 74 010-030 0 <1 170 170 36 120-260BUN148 150 27 110-210 1<3 3 <6 167 160 38 173170 38 110-260 100-230 147 140 40 152 150 31 80-240 100-230 26 173 210 64 100-210 Fvalue=0.1,p= 95 135 135 006 130-140 Flue=02,p= 87 0 <1 Creatinine 10 09 02 08-16 LI LI 02 07-13 1<3 3 <6 0909 01 07-L1 09 09 01 07-10 LI Ll 02 09-16 LI Ll 01 08-12 26 08 0Fv8alue 0=42.7, p0=60-0049 13 13 02 12-16 Fralue =38,p= 01 001127 PoFpOmS) 0 <1 1 <3 3 <6 26 0 <1 1 <3 3 <6 26 0 <1 1 <3 3 <6 26 0 <1 1 <3 3 <6 26 0 <1 1 <3 3 <6 26 "Table 6 (continued) Mean MAendtweSrDp Range Mean MedDecaStuDr 83 83 8 Glucose 66-103 90 86 28 82 81 13 60 -126 93 89 25 80 82 9 66-101 89 89 14 7"2 71-74 Fvalue=1.3,p=.29 93 2 12 Fvalue =0.1,p=.94 Range 66-170 6- 27 60 66-114 83-105 220 219 206 211 217 215 23 Fvalue 221 =06, Cholesterol S50 100 -340 215 208 49 118-315 221 218 30 178 - 266 209 213 16 208 - 240 p= 61 206 206 Falue= 0.5, 39 39 42 47 p=.69 154-276 132-300 128-278 160 - 251 140 138 131 124 143 139 144 136 Fvalue =0.4, LDL 45 29-261 46 4-220 27 99-189 20 130-168 p=.76 139 130 136 136 131128 139 142 Fualue=0.1, 38 36 41 42 p=.94 79-192 62-234 65-190 95-178 HDL 56 57 13 31-94 53 51 13 33-79 43 41 9 45 44 12 50 49 11 31-74 39 39 9 5F3value=419.1, 7 p=235 48-61 39 39 Fva1l4,upe=.=25 5 31-59 26-94 23-51 34-46 Triglycerides ur? 93 98 41-622 105 75 65 41-368 167 151 191 146 126 112 64 34-278 199 198 129 116 52 85-187 Fvalue=03, p=.81 135 153 Fvalue =0.5, 94 114 99 48 p=.67 62-307 61-651 78-413 64-168 001128 Table 6 (continued) PFOS (ppm Antwerp Mean Med SD Range Decatur Mean Med SD Range 0 <1 aa 2 wsHematocri4t6 4s 2 43.50 <3 3 <6 46 47 2 8 47 2 a5 as as as 3 46 46 3 38-52 41-52 26 4748 Fale= LS, 1 p=23. d6-48 46 Fualue=03, 46 p= 83 2 44-49 0 <1 IS5 155 08 140-`1He6m7oglobi1n55 154 07 145-164 1<3 3 <6 152 153 07 156 156 05 138-166 146-167 S01 ISI LI 153 153 10 130-174 136-174 26 154 154 06 148-160 Fualue=14, p= 26 155 156 08 147-162 Fualue=07, p= 58 0 <1 49 50 03 43-57 RBC SI 51 02 48-55 1<3 3 <6 49 49 02 43.54 50 50 02 47-53 49 49 03 43-57 50 49 03 46-55 26 47 49 Falue= 09, 06 40-52 52 51 p= 46 Fualue=1.1,p=.35 04 48-57 0<1 3Ls 313 1S 277-343MCH307 307 16 287-335 1<3 3 <6 312 310 12 315 319 12 295-343 290-333 307 309 LS 309 312 17 264-331 260-336 26 330 325 37 296-369 Fualue= 14, p=.25 299 304 12 282-307 Fualue=04, p= 74 0<1 329 330 06 319-34M5CHC338 339 06 329-347 1<3 3 <6 329 328 06 328 327 07 317-338 313-342 333 333 05 334 334 06 319-345 321-343 26 326 Fualue 324 =04, 05 p=.78 322-31 335 334 03 333-340 Fualue =22, p=.10 001129 Tabl6e (continued) PFOS (ppm Antwerp Mean Med SD Range Decatur Mean Med SD Range 0<1 9% 9 5 85-106 Mev 91 90 4 85-99 <3 3 <6 95 95 3 9% 97 4 90-104 88-14 92 93 4 92 92 5 0-100 si. 26 100 9% 12 91-5 Fualue=18, p=.16 8 9% 3 5-9 Falue =08, p=.50 0 <1 1<3 59 57 13 41-94WBC 68 69 LI 50-90 61 61 13 38-88 75 70 22 36-155 3 <6 26 75 69 65 64 25 02 41-133 64-67 77 74 74 714 0149 4699-.17185 Fualue=45, p= 006 Fralue=05, p=.72 0 <1 24 222 42 159-309Platelet2s33 246 35 162-271 1<3 3 <6 22 20 41 BT 234 52 153-318 12-34 233 25 50 218 204 34 122-367 172-287 26 162 15136 132-202 Evalue=26, p=.06 202 194 56 143-277 Fal= 1e0, p= 40 "Sample sizes: ECOS Level Antwerp 0 <lppm 34 I<3pm 32 3 <6ppm 19 26ppm 3 88 Decatur 1 59 146 % 1. Significantly different exposurecategories. (p < 05, Bonferroni (Dunn) t-test) than the remaining three PFOS 2. Significantly different <3 ppm categories. (p <.05, Bonferroni (Dunn) t-test) than the 0 - < | ppm and the 1 - 3. 4. Significantly Significantly different different (p (p < < 05, 05, Bonferroni Bonferroni (Dunn) (Dunn) t-test) t-test) than than the the 03- < | ppm category. < 6 ppm category. 001130 Tabl7e DemoMgeraanp,hiMce,dSiaenru(mMeCdh)e,miSsttarnideasrdanDdevHieamtaitoonlo(gSiDc)aolfVMaeluaensabnydPRlaanntgLeoocfatPiFoOn,S,1997 PFOS* (ppm) 1997 Data Antwerp Mean Med SD Range Decatur Mean Med SD Range 0-<1 PEOS 046! 037 027 010-094 060' 0.59 026 0.10-097 1-<3 3-<6 L189! 179 061 102-289 L71' 153 052 104-285 387' 366 0.59 322-483 387 351 081 309-530 26 Fv-alu=e-1953, - - p = 0001 F72a0l'ue6=62818.1,15p9=.0600051-993 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 2 28 6 21-50 Age B49 me 37 31 9 u.6 45 45 8 31-62 37 31 SL 3 32.40 - 45 2 44 45 4 9 36-54 29.5 Fvalu=e 10p.= 0400,1 Flue =0.5, p=.69 08 05 10 Alcohol 00-43 02 01 04 01-20 L007 LI 00-50 01 01 01 01-03 22 14 =. 23 00-71 - 01 02 01 01 01 03 01-03 01-08 Fvalue=43, p=.02 Fvalue =038, p=.49 29 219 21 202-283 BMI293 289 49 224-417 242 239 28 236 249 31 181-304 192-283 300 290 60 300 293 30 202-485 254-360 -o - Falue=20, p=.15 308 207 40 261-362 Flue =02,p= 91 001131 PFOS (ppm) 0-<1 1-<3 3-<6 26 (cToantbiln7ueed) -- Awwep__D __ emw Mean Med SD Range Mean Med SD Range 42 00 67 73 20 81 5 00 78 - - - F=13,p=28 Cigareties 0-20 53 00 0-20 87 00 0-20 33 00 - 60 00 Fvalue=08, 11.6 0-40 130 0-40 90 0-30 134 0-30 p=.51 0-<1 1-<3 3-<6 26 69 68 74 74 64 59 - - Fvalue=15, Alkaline Phosphatase 14 49-110 86 84 16 16 41-113 88 83 26 2 29-120 85 83 15 - - 88 84 18 p=.22 Fvalue=0.1,p=.96 55-132 41-163 61-109 65-114 0-<1 1-<3 3-<6 26 GGT 21 17 10 10-50 36 32 25 34 24 34 10- 144 37 n 33 25 22 10 14-43 31 28 15 - - - - 33 37 12 Fvalue =2.5,p=.09 Fvalue=0.2,p=.91 13-142 13-179 13-71 17-48 0-<1 1-<3 3-<6 26 27 26 7 17-53 27 25 7 15-48 25 24 4 19-30 - - - - Fvalue =0.2,p =.80 AST 26 25 7 26 25 17 25 23 9 29 28 3 Fvalue=04,p=.77 13-48 18-56 14-43 26-34 001132 PFOS. (opm) 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1.<3 3-<6 26 Tabl7e (continued) Antwerp Mean Med SD Range Decatur Mean Med SD Range 00025 12 13-60 ALT 3 31 1 17-57 33 16 13-87 28 23 10 14-46 328 16 10-89 303 2a 17-82 So - F value =06,p=.58 414510 25-49 Fale=09, p= 45 090 080 046 040To-t2a3l0Bilir0ub6i3n 060 030 030-140 068 070 023 030-130 079 070 040 030-130 056 050 0.18 030-100 051 050 016 030-090 .Fvalue=23,p=.11 - 058 0.50 024 040-100 Falue=10,p4=1 016 020 008 DirectBilirubin 010-040 0.13 010 006 010-030 013 010 005 010-020 014 010 005 010-020 0.11 0.10 003 010-020 0.11 010 003 0.0-020 . CT - Fvalue=22,p=.12 010 010 000 0.10-0.0 Fvalue= 1.3, p=.28 143 140 21 110-19B0UN 147 140 33 90-210 152 150 26 160 160 27 100-200 120-200 135 135 35 143 140 30 60-260 90-190 ME - Falue=2.1, p=.13 138 120 41 90-190 Fualue=07, p=_56 0-<1 1-<3 09 09 01 07-12 09 09 01 07-13 10 10 01 06-12 10 10 01 07-13 3-<6 26 09 09 01 08-11 .- - 10 10 01 07-11 10 09 02 08-14 Fvalue =03,p=76 Falue=02,p= 89 001133 PFOS (opm) 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 Tabl7e (continued) Antwerp Mean Med SD Range Decatur Mean Med SD Range 81 8 10 Glucose 63-14 93 91 2 58.174 79 78 9 84 85 8 65-100 74-9 102 89 47 75-303 103 93 30 79-192 - So - Fvalue =08,p= 47 89 88 7 80-97 Fvalue =05,p= 67 193190 41 Cholesterol 110-277 204 208 38 145-277 213 205 48 28 223 38 116-365 192-321 218 226 39 230 230 23 152-290 197-280 on - Fvalue =29,p=.07 29 238 26 186-250 Fvalue=20, p=.13 122 114 35 57-205 LDL 127 133 33 50-178 43134 42 67-290 147 141 24 11-195 139 135 35 149 144 25 61-19 113-196 - = - Fvalue=30, p= 06 145 156 26 103-164 Fvalue=16,p=.19 S150 12 19-74 HDL 2 4 9 26-59 48 46 10 34-68 SL 50 10 39-69 42 4 10 28-69 4s 4510 32.62 - So - Fvalue =08, p=.47 40 38 4 37.45 Falue =05,p= 67 99 92 41 Triglycerides 38-175 200 128 219 46-1209 1295 SB 44-290 10 122 88 65-362 185 147 124 63-53 179 183 98 45-394 PE - Fvalue=29, p=.06 20 191 8 149-352 Fvalue=0.1,p=.95 001134 Tabl7e (continued) POS (ppm) Mean Antwerp Med SD Range Decatur Mean Med SD Range 0-<1 1.<3 47 413 46 47 3 a.Hematocri4t6 45 2 40-53 46 46 3 40-50 39.51 3-<6 26 46 45 3 a 42.50 - 44 44 2 39.48 454 2 pew Fualue=07, p=51 Fralue=16, p=.18 0-<1 156 155 08 Hemoglobin 142-170 154 154 07 135-169 1-<3 3-<6 154 156 10 152 147 10 133-173 140-167 154 155 09 148 147 10 135-173 125-165 26 - LY Fualue=07, p= 48 151 150 08 141-162 Fualue=17, p=.18 0-<1 5152 04 46-59 RBCSI S103 43-57 1-<3 3-<6 50 49 S103 48 04 41-55 44-57 51 50 51 50 03 03 42-55 45-54 26 Se Fualue=17, p=.19 - F5u0alue4=904, 0p3=.78 47-55 0-<1 304 304 13 279-335McH303 302 18 276-341 1-<3 3-<6 306 309 305 34 09 14 292.328 288-327 306 306 14 297 305 22 267-338 262-329 26 So Fvalue=09, p= 40 - F30u5al3u0e5=120=1,4p1 275-334 0-<1 334 334 05 322.34M0CHC338 387 05 328-349 1-<3 3-<6 333 332 05 334 335 05 318-341 324-343 338 338 05 336 339 08 327-346 320-344 26 Fualue=0 06, p=.54 - 339 339 05 334-346 Falue=06, p=.62 001135 PFOS (ppm) 0-<1 1-<3 3-<6 26 Table7 (continued) Antwerp Mean Med SD Range Decatur Mean Med SD Range Mev 91 91 4 92 92 3 84-100 87.9 985 91 90 4 83.101 81-9 93 95 5 86-97 So . . 88 8 5 80-9 0 91 6 81-9 Fvalu=e 13,p=.29 Fvalue=p0=94,5 0-<1 60 57 13 38-88WBC 63 59 16 40-103 1-<3 3-<6 71 68 22 44-132 64 60 18 42-100 67 66 61 61 16 38-101 13 40-89 26 oo Fvalue =2.6,p= 08 . 62 71 15 42.74 Fale =08,p=.51 0-<1 237 232 SS 126-40Pl6atelets215 207 SO 106-363 1-<3 3-<6 243 232 48 215 225 41 151-359 147-263 209 210 48 224 219 50 124-323 159-316 26 oT . - Fvalue=LLp=35 199 191 58 146-295 Eval=u0e3,p=80 *Samplesizes: FCOS Level Antwerp 0-<lppm 31 1-<3ppm 25 3-<6ppm 9 26ppm 0 65 Decatur 29 38 12 5 84 1. Significantlydifferent (<p PFOS exposure categories. 05, Bonferroni (Dunn) t-test) than the remaining three 2. Significantly different 1-<3 ppm categories. (p < 05, Bonferroni (Dunn) t-test) than the 0 - < I ppm and the 3. Significantly different category. (p < 05, Bonferroni (Dunn) t-test) than the 0 - < 1 ppm 001136 Table Multivariable Regression of Serum Chemistries and Hematological Parameters - Examinationof the Effect of PFOS Adjusting for Age, Alcohol, BMI and Cigarettes, `Antwerp and Decatur Data Combined, 1995 and 1997 Examinations Intercept PFOS Age Alcohol BMI Cigarettes Parameter 5299 032 008 5.43 104 0.85 R'=.26 Alkaline Phosphatase 1995 Data 1997 Data SE. b value Parameter SE pValue 1.14 0001 40.87 9.60 0001 089 7 0.19 103 86 020 68 04s [3 ol 153 0005 209 161 20 034 002 069 034 04 015 0001 049 015 002 AdjR'=24 RP=.19 AdjR?=.16 Intercept PFOS Age Alcohol BMI Cigareties Parameter 2.3816 00032 0.0040 0.0605 00372 0.0076 R*=.14 1995 Data SE 0.2711 00217 0.0048 00373 00082 0.0038 AdjR*=.12 InGGT p value 0001 88 Aa a1 0001 05 Parameter 2.0471 0.0178 0.0036 0.0747 0.0365 0.0030 R'=.15 997 Data __SE b value 02592 0001 00280 53 0.0049 a1 00438 09 0.0091 0001 00042 48 AdjR'=.12 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 1262 042 0.0005 0.70 054 0.11 R*=.08 1995 Data AST 1997 Data SE p value Parameter SE p value 552 02 2325 3.50 0001 044 35 Em 038 m 0.10 9 0.07 007 29 076 36 040 059 50 017 002 023 012 07 008 4 007 006 20 Adj R*= 05 R'=04 Adj R?=.00] 001137 `Table 8 (continued) Intercept PFOS. Age Alcohol BMI Cigarettes Parameter 28.54 0.09 0.18 0.16 0.96 0.14 R*= 08 1995 Data SE 9.46 0.76 017 130 029 013 AdjR'= 05 ALT Dvalue Parameter 003 11.60 0 0.97 28 0.19 9 031 001 100 28 2009 R=13 1997 Data __SE 6.78 073 0.13 L14 024 oll AdjR?=.10 p value 0 19 14 79 0001 40 Intercept PFOS PFOS? Age Alcohol BMI Cigarettes Parameter 0.2742 0.0984 0.0086 0.0052 0.0738 00273 00158 R'=32 1995 Data SE 0.1958 00368 0.0039 0.0035 0.0268 00059 0.0028 AdjR'= 30 In Total Bilirubin D value 16 008 03 14 007 0001 0001 Parameter 0.1395 0.1620 0.0188 0.0015 0.1220 00097 200054 Ri=.18 1997 Data __SE 0.1945 00515 0.0070 00037 00327 0.0068 00031 Adj=i1R4 D value 41 002 009 70 0003 16 09 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 0.2196 00009 0.0006 0.0074 00012 0.0007 R*=.06 Direct Bilirubin 995 Data SE D value 1997 Data Parameter __SE D value 0.0259 0001 00021 68 0.1929 0.0264 0001 00061 0.0029 03 0.0005 17 0.0036 04 0.0002 00005 69 0.0106 0.0045 02 0.0008 13 ___0,0004 06 00017 0.0009 01 00009 00004 05 AdjR*=.03 R'=.14 AdjR*=.11 001138 Table 8 (continued) Intercept PFOS Age Alcohol BMI Cigarettes Parameter 18.64 002 0.03 037 005 0.08 R'=.08 995 Data SE. 1.94 015 003 027 0.06 03 AdjR=.05) BUN D value "0001 1 39 a7 42 004 Parameter 13.22 0.08 0.08 0.50 007 -005 R=.09 1997 Data. __SE 147 0.16 0.03 025 005 002 Adj R= 06) b value 0001 60 005 05 20 05 Intercept PFOS PFOS? Age Alcohol BMI Cigarettes Parameter 0.5744 00223 0.0033 0.0059 -0.0260 0.0086 0.0005 R'=29 1995 Data SE 0.0779 00146 00016 00013 0.0106 0.0023 0.0011 AdjR= 27 Creatinine pvalue 0001 13 04 0001 0 0003 65 Parameter 0.9478 00302 0.0055 0.0027 00242 00022 00019 R*=.16 1997 Data. __SE 0.0602 00159 0.0022 0.0012 00101 00021 00010 AdjR*=.13 D value 0001 06 01 002 02 30 05 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 3.8943 00039 0.0045 0.0026 0.0143 0.0003 R'=31 1995 Data SE. 00732 00058 0.0013 00101 00022 0.0010 Adj R= 29) IGnlucose p value 0001 51 0006 9 0001 78 Parameter 3.8597 0.0014 0.0025 0.0068 00195 00013 R'=.30 1997 Data. __SE 0.0919 0.0098 0.0017 0.0154 00032 00015 Adj R= 27 D value 20001 39 15 66 0001 39 001139 Intercept PFOS Age Alcohol BMI Cigareties Parameter 190.1 099 074 0.40 0.04 0,18 R?=.02 `Table 8 (continued) 1995 Data _SE 221 177 039 304 067 031 AdjR7= 00 Cholesterol pvalie 0001 58 06 90 95 36 Parameter 1555 4.66 139 7.50 -040 -008 Ri=.17 1997 Data SE 190 204 036 318 067 030 AdjR*= 14) D value 0001 0 0002 02 55 80 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 135.26 0.50 0.58 3.33 6.67 0.52 R'=05 1995 Data LDL 1997 Data. _SE 2027 b value 0001 Parameter SE 114.69 17.06 D value 0001 1.61 76 0.36 11 401 182 03 104 032 002 278 2 061 28 429 284 13 109 060 07 028 01 AdR'=.02 002 R'=13 028 95 AdiR=.10 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 70.82 -L17 0.11 3.53 -063 0,17 R*=28 1995 Data HDL 1997 Data SE 573 D value Parameter __SE 0001 66.71 4.52 D value 0001 046 01 0.10 21 022 049 65 012 009 17 079 017 0001 201 076 0004 095 016 009 0001 008 003 016 007 03 AdjR*= 26 R*=29 AdjR*=.26 001140 Intercept PFOS Age Alcohol BMI Cigarettes Parameter -10329 -L78 154 0.43 671 2.70. R=24 `Table 8 (continued) ! 1995 Data Triglycerides 1997 Data. SE 45.97 D value Parameter __SE 03 "18799 58.18 p value 002 3.68 63 033 628 9% 082 06 137 LiL 2 632 95 14.68 982 14 139 0001 10.06 205 0001 064 0001 187 094 05 AdjR?= 22 R=.23 AdjR= 20 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 48.01 0.06 0.0005 0.10 -008 0,05 R*= 08 1995 Data Hematocrit 1997 Data SE 136 bvalue Parameter __SE 0001 46.73 128 D value 0001 oll 57 002 9 025 [a 07 0.03 002 20 019 58 0.04 06 015 022 0.50 001 005 075 002 007 004 002 0 AdjR7= 05 R= 08 Adj R*= 04 -- Intercept Pa1r5a.7m8eter PFOS -002 Age 0.004 Alcohol 0.02 BMI 0.03 Cigareties 0.02 R*=.06 1995 Data Hemoglobin S04E5 pv10a0l01ue 0.04 53 0.008 57 0.06 7 001 06 0.006 0 Adj R?=.03 Pa1r5a.4m3eter 008 0.006 001 0.008 002 R'=.06 997 Data. S0E43 pv00a0l1ue 005 07 001 46 007 85 002 59 0.007 03 Adj R?=.03 001141 Intercept PFOS Age Alcohol BMI Cigareties Parameter 4.8766 00026 00022 -00323 0.0069 0.0006 R'=.04 Table 8 (continued) 1995 Data RBC 1997 Data. _SE 0.1559 value Parameter SE 0001 5.1416 0.1626 D value 0001 00123 8 00208 0.1756 24 00028 a 00068 0.0031 0 00213 13 00U1 00274 69 0.0047 14 0.0022 7 0.0089 0.0057 12 00025 00026 35 Adj R*=.01 R*=.06 Adj R= 02] Intercept PFOS Age Alcohol BMI Cigarettes Parameter 32.292 0.015 023 0.189 0.093 0.0347 R'=20 1995 Data MCH 1997 Data _SE. p value Parameter __SE D value 0725 0058 0001 79 30.062 0.706 0.047 0076 0001 54 0013 08 0028 0013 04 0.099 06 0.095 0.119 a3 0022 0010 0001 001 0.035 0025 0.046 0011 16 0001 AdjR'=.18 R*=.13 Adj R*=.10 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 328525 00015 0.0097 0.1121 20.0006 0,004] R?=.07 1995 Data MCHC SE. D value Parameter 0.3341 10001 330100 0.0266 96 00092 0.0059 a1 00101 0.0458 02 0058 00100 95 0.0072 00047 39 0.0016 AdjR*=.05 R*=.07 1997 Data SE b value 02675 0001 00289 75 0.0051 05 0.0451 19 0.0094 45 00043 h) AdiR*=.04 001142 Intercept PFOS Age Alcohol BMI Cigareties Parameter 98.29 -003 0.04 0.88 028 0.12 R'=23 Table 8 (continued) 1995 Data Mev 1997 Data. SE. 229 D value 0001 Parameter __SE 90.91 1.98 D value 10001 0.18 88 004 33 009 021 0.06 004 67 1s 031 007 o 049 033 0001 0.12 007 14 08 003 0005 013 003 0001 AdjR*= 21 Ri=.15 AdjR*=.12] Inercept PFOS Age Alcohol BMI Cigarettes Parameter 272.49 337 0.88 4.80 0.04 021 R*=.06 1995 Data Platelets 1997 Data SE 2337 p value Parameter __SE 0001 260.92 2527 D value 0001 186 07 041 04 291 273 2 025 048 61 320 14 070 95 237 426 58 073 0.89 a 033 052 -030 041 46 AdjR*=.03 R*=.03 Adj R?= 00 Intercept PFOS Age Alcohol BMI Cigarettes 1995 Data WBC 1997 Data. Parameter SE 3.9538 08120 p value 0001 Parameter __SE 5.1296 0.6927 p value 0001 0.0893 0.0646 7 0.0214 00144. 14 00048 00748 95 00139 00132 30 0.0860 0.1111 a4 0.0492 00244 05 02471 0.1169 04 0.0045 0.0244 86 0.1009 0011s 000] 0.0878 00111 0001 R*=36 AdjR*= 34 R'=133 Adj R= 31 001143 Table 9 Multivariable RegressionofTotal Bilirubin, Direct Heamtocrit, Hemoglobin and Platelets- EBxilaimriunbaitn,ioCnreoaftitnhienEefCfheoclteosftePrFolO,SLDL, HDL, Adjusting for Age, Alcohol, BMI and Cigarettes, by Location, 1995 and 1997 In Total Bilirubin - Both Locations Intercept PFOS PFOS? Age Alcohol BMI Cigaretles Parameter 0.2742 00984 0.0086 0.0052 0.0738 00273 0.0158 Ri=.32 1995 Data SE 0.1958 00368 0.0039 0.0035 00268 00059 0.0028 Adj R?= 30 Dvalue 16 008 03 14 007 0001 0001 Parameter 0.1395 0.1620 0.0188 0.0015 0.1220 00097 0.0054 RP=.18 1997 Data __SE 0.1945 00515 0.0070 0.0037 0.0327 0.0068 0.0031 AdjR'=.14 p value a7 002 009 70 0003 16 0 In Total Bilirubin - Antwerp Only Intercept PFOS. PROS? Age Alcohol BMI Cigarettes 1995 Data Parameter SE 0.0776 0.0475 0.0473 00575 0.0035 00072 0.0062 0.0055 0.0398 00316 00115 00161 0.0176 ___ 0.0056 R'=.15 AdjR'=.08 D value 85 4 63 21 21 48 002 1997 Data Parameter __SE p value "03130 05586 0.58 02157 01779 00336 00385 23 39 -00036 0.0081 0.0826 0.0441 66 07 00114 00222 00102 00074 61 7 R'=.l4 AdR=.05 Intercept PFOS PFOS? Age Alcohol BMI Cigarettes In Total Bilirubin - Decatur Only 1995 Data Parameter SE pvalue -04462 00862 03154 00509 16 09 0.0081 00128 0.0048 0.0048 10 ol 00045 0.0828 59 00179 0.0068 ol -00117___ 0.0031 0004 R'=29 AdjR'=24 1997 Data. Parameter SE b value 0.9486 0.2932 002 0.1160 00578 05 0.0144 00134 0.0072 0.0046 05 005 0.1708 0.1607 29 00045 0.0073 54 00031 00032 33 R=.17 Adj R?=.10] 001144 Intercept PFOS Age Alcohol BMI Cigarettes Table 9 (continued) HDL - Both 1995 Parameter Data __SE (N = 178) D value 70.82 573 0001 -L17 046 0.11 0.10 or 21 3.53 079 0001 063 017 0.17 0.08 0004 003 R'=28 AdR'=26 Locations 1997 Data(N = 149) Parameter SE 66.71 4.52 D value 0001 022 049 or 0.09 65 17 201 0.76 009 0.95 0.16 0.16 007 0001 03 R'=28 AdiR'=26 Intercept PFOS Age Alcohol BMI Cigarettes HDL -Antwerp Only 1995 Data (N = 86) Parameter SE b value 73.44 -155 12.69 073 0001 04 001 017 9 331 087 098 050 001 09 0.19 017 28 R*=.16 AiR =.11 Parameter 1997 Data SE (N = 63) b value 57.30 1212 0001 2.26 117 06 043 017 o1 278 099 082 048 007 10 045 0.16 007 R?=28 AdjR= 21 Intercept PFOS Age Alcohol BMI Cigarettes HDDLe-catuOnrly 1995 Data (N=85) Parameter SE D value 66.35 9.42 075 0.60 20001 2 0.14 014 32 4.71 248 06 049 021 02 0,16 009 0 R=.14 AdjR*=.09 1997 Data (N = 83; Parameter SE D value 69.17 701 017 050 0001 73 001 oll 96 3.07 387 0.90 018 43 0001 0.04 008 61 R'=27 Adj R= 22 001145 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 27249 337 0.88 4.80 0.04 021 R= 06 Table 9 (continued) Platelets - Both Locations 1995 Data SE 2337 186 041 320 0.70 033 AdjR?=.03] b value 0001 07 04 14 95 S52 Parameter 260.92 291 025 237 073 030 R=.03 1997 Data. __SE 2527 273 048 4.26 089 041 Adj R?= 00 D value 0001 29 61 58 al 46 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 294.81 257 035 3.65 223 0.82 R'=.06 Platelets. Antwerp Only 1995 Data __SE 48.19 277 065 374 191 065 Adj R?=.00 D value 0001 36 60 33 25 21 Parameter 25821 -199 0.41 0.87 -L16 0.70 R'=.02 1997 Data. SE 66.58 644 091 542 2.65 090 Adj R= 00 D value 0003 76 65 87 66 44 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 353.90 6.08 1.99 5.36 0.64 035 R'=19 Platelets,DecaturOnly 1995 Data SE p value 39.04 0001 2.50 02 059 001 10.14 60 084 45 040 38 AGR=.14 Parameter 225.66 275 -0.16 8.45 0.14 019 R'=01 1997 Data. __SE 42.96 3.09 0.69 2.70 110 047 AdR=.00 D value 0001 38 82 72 20 69. 001146 Intercept PFOS. PFOS Age Alcohol BMI Cigarettes Parameter 0.5744 00223 0.0033 0.0059 0.0260 0.0086 00005 R'=29 Table 9 (continued) Creatinine - Both Locations 1995 Data _SE 00779 00146 0.0016 0.0013 0.0106 0.0023 0.0011 AdjR*=27 D value 0001 3 04 0001 0 0003 65 Parameter 0.9478 00302 0.0055 0.0027 00242 0002 -00019 R'=.16 1997 Data SE 0.0602 00159 0.0022 0.0012 00101 00021 00010 AdjR*=.13 D value 0001 06 01 002 02 30 05 --Int-- ercept Pa0.r7a3m1e9ter PFOS 00324 PFOS* 0.0008 Age 0.0044 Alcohol ~~ -00055 BMI 0.0037 Cigarettes 0.0017 R'=.20 Creatinine - Antwerp Only 1995 Data S0E .1382 p0v0a0l1ue 00195 10 0.0024 74 0.0019 02 00107 61 0.0055 50 0.0019. 36 Adj R*=.14, Pa0r.8a6m0e0ter 00453 0.0074 0.0033 00142 00012 0.004 R'=.14 1997 Data S0.E1430 pv0a00l1ue 00455 2 0.0099 46 0.0021 11 00113 21 00057 8 00019 04 Adj R?= 05 -- Intercept Pa0.a8m64e1ter PFOS -0.0093 PFOS? 0.0036 Age 00032 Alcohol 0.0082 BMI 0.0032 Cigarettes 00030 003 R'=.23 1995 Data S0E.1300 0.0206 0.0019 0.0020 0.0336 00028 0.0013 Creatinine - Decatur Only p0v00a1 e 65 07 1 81 26 02 Pa1a.1m36e3ter 00430 0.0067 0.0006 0.1133 00038 0.0034 AdjR'=.18 R*=.27 1997 Data. S0.E1021 pa00l01e 00201 04 00025 009 0.0016 7 00559 05 0.0026 14 00011 AdjR?= 22 001147 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 190.1 099 074 040 0.04 0.18 RP=.02 Table 9 (continued) Cholesterol- Both Locations 1995 Data SE 21 177 039 304 067 031 AdjR*= 00 p value 0001 58 06 20 95 56 1997 Data Parameter __SE p value 155.5 19.0 0001 4.66 204 0 139 0.36 0002 7.50 3.18 0 040 067 55 0.08 030 80 R'=.17 AdjR = 14) _I_ntercept PFOS Age Alcohol BMI Cigareties Pa62m.m17eter 122 2.60 LI3 228 0.8 R'=25 Cholesterol - Antwerp Only 1995 Data S4E372 251 059 339 1.73 059 p1v6alue Kk 0001 74 19 7 AdjR*= 20 Pa9m3.m1e1 ter 237 254 749 078 -023 Rf=33 1997 Data S4E9.20 474 067 3.98 195 066 pv0a6lue 62 0004 06 9 7 AdjR?= 27 Chole-sDetcaeturrOonlly -- Parameter 1S9E95Daa p value Intercept 304.27 3314 0001 PFOS -1.03 219 64 Age -105 051 4 Alcohol 2116 888 02 BMI 103 73 17 Cigarettes 0.40 033 23 RI=14 AGR=09 -- Para1 mete9 r 9__S7 E Dat p vaa lue 207.01 3155 0001 426 227 06 048 051 35 19.54 17.41 27 -78 081 34 011 35 as RP=07 AR =0l 001148 Intercept PFOS Age Alcohol BMI Cigareties Parameter 135.26 0.50 0.58 333 6.67 0.52 R*=.05 Table 9 (continued) 1995 Data SE 2027 161 036 278 061 028 AdjR*= 02 LDL p value 0001 76 it 2 28 01 Parameter 114.69 401 1.04 429 109 002 R'=.13 1997 Data. __SE 17.06 182 032 284 0.60 028 AdjR?=.10 b value 0001 03 002 13 07 95 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 12.14 024 215 3.04 204 0.35 R=20 LDL -AntwerpOnly 1995 Data SE 4144 238 0.56 321 164 056 AdjR?=15) pvalue 7 92 0003 35 2 53 Parameter 40.88 150 22 412 048 026 R'=29 1997 Data __SE 242 4.08 058 343 168 057 Adj R= 23] p value 34 7 0003 2 78 65 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 218.24 1.06 079 22.95 "138 0.65 R'=.20 1995 Data SE. D value 3058 0001 1.96 59 046 Ka 804 006 067 4 030 03 AdjR'=.15 1997 Data Parameter __SE D value 160.50 28.17 0001 355 203 08 020 045 65 -1268 2872 66 127 072 08 013 031 61 R*=.07 Adj R= 01 001149 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 48.01 006 0.0005 0.10 -008 0.05 R*=.08 Table 9 (continued) 1995 DataHema-tBoothcLorcatiiotns SE pvalue Parameter 1.36 0001 46.73 0.11 57 025 002 98 0.03 0.19 58 015 0.04 06 001 002 007 004 Adj R?= 05 R= 08 1997 Data __SE 128 014 002 022 005 002 AdjR*= 04 p value 0001 07 20 0.50 075 04 Intercept PFOS. Age Alcohol BMI Cigarettes Parameter 44.00 006 0.06 0.12 002 0.05 R?=.08 Hemat- Aontcwerrp Ointly 1995 Data SE D value 230 0001 013 63 003 06 018 51 009 80 003 14 Adj R? = 03 Parameter 4563 029 004 0.06 -002 001 R*= 01 1997 Data __SE 3.63 035 0.50 030 014 00s Adj R?=.00 b value 10001 a 37 ET 89 29 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 45.56 -005 001 0.56 002 0,08 R'=.10 Hemat-DoeccatrurOintly 1995 Data SE 262 017 0.04 0.68 0.06 003 AdjR'= 04 p value 0001 9 89 41 7 004 Parameter 45.69 028 005 -152 008 0.06 R*=.19 1997 Data SE 1.95 014 003 108 005 002 AdjR'=.13 p value 0001 05 00 16 an 006 001150 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 15.78 0.02 0.004 0.02 003 0.02 R*=06 Table 9 (continued) Hemog-BlothoLobcai tionns 1995 Data SE 045 0.04 0.008 0.06 001 0.006 Adj R= 03 b value 0001 53 57 7 06 0 Parameter 15.43 0.08 -0.006 001 0.008 002 R'=.06 1997 Data. __SE 043 005 001 007 002 0007 Adj R?= 03] b value 0001 07 46 85 59 03 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 14.72 0.008 002 0.04 0.007 0.005 R*=.08 `Hemo-gAnltwoerbpiOnlny 1995 Data SE 074 0.04 001 0.06 003 001 AdjR?=.02] D value 0001 86 02 51 81 61 1997 Data. Parameter SE D value 1532 LIS 0001 0.10 ol 40 002 002 33 002 009 81 0.01 005 81 -0,006 002 20 R*=.03 Adj R= 00 Intercept PFOS Age Alcohol BMI Cigarettes "Hemoglobin- Decatur Only 995 Data Parameter SE D value 15.87 090 0001 0.03 0.06 6 0.004 001 7 0.22 023 35 0.02 0,02 002 2 0009 o1 R'=.10 AdjR*= 04 1997 Data Parameter SE D value 15.58 071 0001 0.10 005 07 0.02 001 2 047 039 23 002 002 002 0.008 25 004 R'=.17 AdjR=.12 001151 Intercept PFOS Age Alcohol BMI Cigarettes Table (continued) Parameter 0.2196 00009 0.0006 0.0074 00012 0.0007 R*=.06 Direct Bilirubin - Both Locations 1995 Data SE. 0.0259 00021 0.0005 0.0036 00008 0.0004 AdjR'=03 D value 0001 68 a7 04 13 06 1997 Data Parameter __SE p value 0.1929 0.0264 0001 00061 00029 03 00002 0.0005 69 0.0106 0.0045 02 00017 0.0009 07 00009 0.0004 05 R'=.14 AdjR'= 11 Intercept PFOS Age Alcohol BMI Cigarettes Direct Bilirubin - Antwerp Only Parameter 0.1794 00034 0.00004 0.0102 0.0017 00016 R'=.17 1995 Data SE. 0.0461 00026 0.0006 0.0036 00018 ___0.0006 AdR'=.12 p value 0002 21 95 006 36 0009 1997 Data. Parameter __SE p value 0.1963 0.0813 02 00077 0.0079 33 00017 0.0011 13 00112 0.0066 10 0.0006 0.0032 84 -00017 00011 12 R'=.14 Adj R*= 06 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 0.1972 0.0025 0.0012 -00114 00016 0.0001 R*=.07 Direct Bilirubin - Decatur Only 1995 Data SE 0.0478 00032 0.0007 00128 0.0011 ___0,0005 AdjR*= 02 D value 0001 4 oll 37 13 9 1997 Data, Parameter __SE D value 0.1205 0.0347 10008 00038 0.0025 13 0.0014 0.0006 02 00042 00191 8 0.0018 0.0009 0 00004 00004 2 R'=.15 AdjR?=.10 001152 ae10 Sammars of Spl Liar and Qui Regression Models orToland Unongaid iin, 195ad 1997 mba eon Bobi BETe 7 Tr i -- a -- FGReSoiemGSna oi GeSwaueonmen Suvi oSewosmeo0 Sgenaom meaoomlesne ets ooiwmnession Canc ooSmwasban toSwiephon Savon saa FfESnaisOSmia os OoSmsRD Sear GSonohw a SSomoeme Cia Gooahem s oSTmhwe o Soin Stomoewton bSSiawmaosn one Row a om om ww om wm om S2[rQE 24 iEmeler p mSoosol lm2s sn 0S66o9m4 an 0A .o39n8i03on D04o821d79eaS n 0o.5m91 0m9es 7 0S68o2u87man 0S4A72e68 il0To38m4H4i0on Table 11 Mean Values of PFOS, Demographic, Serum Chemistry and Hematologic Parameters for Antwerp and Decatur Combined Locations, 1995 and 1997 Examinations for Employees Who Participated and Did Not Participate in Both Years Variable PFOS (ppm), 1995 Data Both Years Only 1995 N=6l) (N=17) 240 208 1997 Data Both Years Only 1997 (N=6) _ (N=88) 234 134 Age El a2 ar 38 BMI 271 263 273 269 Cigarettes 54 61 52 68 Alcohol 08 06 04+ 04 Alk Phosphatase~~ 87 86 7 80 GGT 4" 4" Ed 27 AST 2 2 26 26 ALT 46 46 3 32 `Total bilirubin 071 on 065 069 Direct bilirubin ~~ 0.21 022 013 013 BUN 162 157 146 143 Creatinine 10 10 10 10 Glucose 86 87 9 89 Cholesterol 212 213 225%xx 201 LDL 142 134 Laser 128 HDL 50 a 46 4s 001154 Variable 1995 Data Antwerp Decatur Triglycerides 139 157 Hematocrit 45 a7 Hemoglobin 150 155 RBC 49 50 MCH 308 312 MCHC 32 31 Mve 9 9% WBC 66 70 Platelets 26 227 *p<.05; *p<.OL; *+*p<.00l Table 11 (continued) 1997 Data. Antwerp Decatur 167 149 46 46 153 154 50 5.1 308% 302 36 36 oar % 65 64 28 24 001155 Table 12 Mean Values of PFOS, Demographic, Serum Chemistry and Hematologic Parameters for Antwerp and Decatur, 1995 Examinations for Employees Who Participated and Did not Participate in Both 1995 and 1997 Variable PFOS (ppm) Antwerp Both Years Only 1995 TMN=21) (N=61) 230 176 Decatur Both Years Only 1995 N=34) (N=56) 248 242 Age 3 37 ar 46 BMI 240 29 206 290 Cigarettes 54 43 54 94 Alcohol 17% 10 or 02 Alk Phosphatase 75 75 9% 9% GGT 46 39 4 50 AST 2 25 30 29 ALT a3 as 48 a7 Total bilirubin 091 084 054 059 Directbilirubin ~~ 023 022 019 021 BUN 177 167 150 150 Creatinine 09 09 LL 11 Glucose 78 8 92 92 Cholesterol 209 216 230% 209 LDL 133 140 150+ 128 HDL 56 53 46 a2 001156 Table 12 (continued) Varigble _A_n_w1er9p95DaDaecatur _An_tw_er1p 997DeDcaatuar Triglycerides 100 12 170 197 Hematocrit 46 a aan 46 Hemoglobin 153 15 1480 154 RBC 49 49 49 50 MCH 312 31s 305 308 MCHC 30 328 34 334 Mve 95 % ot 2 WBC 64 63 68+ 78 Platelets 22 25 230 28 *p<.05; **p<Ol *+*p<.001 001157 Table 13 Mean Values of PFOS, Demographic, Serum Chemistry and Hematologic Parameters for Antwerp and Decatur, 1997 Examinations for Employees Who Participated and Did not Participate in Both Years Variable PFOS (ppm) Antwerp Both Years Only 1997 ON=27) (N=38) 233% 088 Decatur. Both Years Only 1997 N=34) (N=50) 235 1.69 Age 37x 30 4s 4" BMI 244 238 295 209 Cigarettes 59 52 47 79 Alcohol 10 07 ol 02 Alk Phosphatase 72 69 85 88 GGT 3 21 41 32 AST 27 26 26 2 ALT 32 30 3 34 Total bilirubin 077 081 0.56 059 Direct bilirubin ~~ 0.14 0.16 012 oll BUN 152 146 14.1 140 Creatinine 09 09 10 10 Glucose 80 81 103 95 Cholesterol 224n0x 192 26+ 208 LDL 148 123 143 132 HDL 51 49 43 2 001158 Table 13 (continued) Variable 995 Data Antwerp Decatur 1997 Data Antwerp Decatur Triglycerides 125 101 201 185 Hematocrit 46 6 4s 46 Hemoglobin 15.5 154 152 154 RBC 50 51 49% s.1 MCH 308 304 309 300 MCHC 334 33 37 338 mvc 92 91 or 89 WBC 68 63 64 65 Platelets 241 234 218 217 *p<0S; **p<.Ol; *p< 001 001159 Table 14 Multivariable Regression of Serum Chemistries and Hematological Parameters - Examination of the Effect of PFOS Adjusting for Age, Alcohol, BMI and Cigarettes, Antwerp and Decatur Employees (N = 61) Who Participated in Both the 1995 and 1997 Examinations Intercept PFOS. Age Alcohol BMI Cigarettes Parameter 55.23 171 042 534 070 0.82 Ri=24 1995 Data SE. 222 177 043 247 067 034 AdiR*=.17 Alkaline Phospatase D value 02 34 33 04 30 02 Parameter 45.74 046 033 2.93 062 076 Ri=.15 1997 Data. __SE 2207 171 037 236 061 032 AdjR?=.07 b value 04 79 37 2 31 0 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 2.5359 00028 00078 0.0795 0.0469 0.0023 R'=.14 1995 Data InGGT 1997 Data. SE D value Parameter __SE D value 0.5561 0001 2.5660 0.5965 0001 00443 95 00357 00461 44 00107 47 0.0619 20 00095 0.0010 35 0.0673 0.0638 30 00167 007 0.0463 00165 007 0.0084 9 00025 0.0087 71 AdjR*=.06) R'=.14 Adj R= 07 Intercept PFOS Age Alcohol BMI Cigareties Parameter 15.27 040 017 101 024 026 R7=.08 1995 Data scot 1997 Data SE pvalue Parameter SE pvalue 1119 18 21.68 6.80 002 089 022 65 a2 022 053 0.001 oll 7 99 125 42 047 73 52 034 017 41 13 017 0.19 007 0.10 38 49 Adj R*= 00 R'=.03 Adj R=.00 001160 Intercept PFOS Age Alcohol BMI Cigarettes Table 14 (continued) 1995 Data sGpT 1997 Data Parameter SE b value Parameter SE pvalue 26.32 1783 15 15.34 13.86 27 003 1.42 98 027 107 20 0.20 034 57 -034 023 14 0.13 1.98 95 022 148 88 105 054 06 Lis 0.38 004 0.25 027 3s 004 020 8 R*=.10 AdjR7=.02 R'=.18 AdjR?=.11 Intercept PFOS PFOS? Age Alcohol BMI Cigareties Parameter 0.7086 -00874 0.0081 00030 0.0344 00319 0.0130 R'=.23 1995 Data SE 03971 00806 0.0068 00073 0.0436 00LIS 0.0060 AdiR'=.14 InTotalBilirubin p value 08 28 24 69 43 o 03 Parameter 03739 0.0202 0.0014 0.0072 0.1045 00182 00105 R*=.19 1997 Data __SE 03996 0.0308 0.0026 0.0068 0.0426 00112 00058 AdjR?=.10] p value 35 51 58 29 0 1 08 Intercept PFOS Age Alcohol BMI Cigareties --Pa--ra--meter 02579 00027 00019 0.0049 0.0010 _-0.0005 R'=.13 DirectBilirubin 1S9E 95Daptvalaue -- Param1 eter99 SE 7DaD va alue 0.0469 0001 0.1711 0.0462 10005 00037 47 00026 0.0036 47 0.0009 04 0.0004 0.0008 60 00052 35 0.0089 0.0049 08 0.0014 49 0.0021 0.0013 10 0.0007 50 -0.0008 0.0007 2 AdR?j= 05 RP=.14 Adj R?=.07 001161 Table 14 (continued) Intercept PFOS Age Alcohol BMI Cigarettes Pa1r8a.3m3eter -009 001 0.59 0.04 0.15 R*=.16 1995 Data BUN S3E62 p0v0a0l1ue Pa1r4.a0m6eter 029 as 029 007 87 007 040 15 0.18 011 a 0.12 005 007 003 AdjR'=.09 R'=.08 1997 Data S3.E00 pv0a0l01ue 024 2 005 16 033 59 0.09 a8 004 55 Adj R= 00 Intercept PFOS PFOS? Age Alcohol BMI Cigarettes Parameter 0.5185 00515 0.0068 0.0073 00100 0.0099 00003 RP=.49 1995 Data Creatinine 1997 Data. SE p value Parameter __SE b value 0.1308 0002 08785 0.1333 0001 00264 06 0.0168 00103 1 0.0022 004 0.0005 0.0009 57 0.0024 004 0.0036 0.0023 12 00143 49 00266 00142 07 00038 ol 00030 00037 a3 0.0019 8 00028 00020 15 AdjR*= 43 R*=.18 Adj R*=.09 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 3.7479 00017 0.0008 0.0050 0.0236 0.0023 R= 46 1995 Data IGnlucose: 1997 Data SE D value Parameter SE D value 0.1311 0001 34111 02013 0001 00103 87 0.0036 00156 82 00025 4 0.0063 0.0034 07 0.0145 7 0.0005 0.0215 9% 0.0039 0001 0.0306 0.0056 0001 00020 26 00051 00029 09 Adj R= 41 RP=.48 AdjR*= 43 001162 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 184.37 "LIS 137 272 024 0.82 R'=.13 Table 14 (continued) 995 Data SE 3459 276 067 385 104 052 Adj R*= 05 Cholesterol p value 0001 68 04 48 81 12 Parameter 179.50 375 073 6.57 009 0.07 R*=.09 1997 Data SE 38.87 301 065 416 107 057 AdjR*= 01 D value 0001 2 27 12 94 20 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 115.89 036 126 374 061 0.72 R=15 1995 Data LoL 1997 Data. SE. p value Parameter __SE p value 3035 10004 150.88 34.90 0001 238 38 268 2.70 33 058 88 044 058 4s 335 21 381 373 31 091 51 "120 096 2 045 2 0.10 05 85 AdjR*= 07 R*=.07 Adj R= 00 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 75.25 0.68 00005 2.31 0.86 030 RP=25 1995 Data HDL 1997 Data __SE. D value Parameter __SE D value 1101 0001 68.22 891 0001 086 44 033 069 63 021 9 ot 0s 47 121 06 2.10 095 03 033 ol 097 025 0002 017 08 012 013 3 Adj R=.18 RP=34 AdjR*=28 001163 Table 14 (continued) _I_nte_rcept PFOS Age Alcohol BMI Cigarettes Pu8a9m.5e2ter 378 072 -1.93 7.50 1.40 R*=.26 1995 Data Triglycerides 1997 Data S66E.79 pu1a9lue Pa1a9m8e0t5er S8E202 pv0a2lue 532 48 7.03 635 21 129 58 087 137 53 743 80 3.28 877 a 200 0004 1126 226 0001 LoL 17 073 119 54 AdjR'=.19 R'=138 AdjR'= 32 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 50.87 003 005 0.00 0.13 0,05 R'=.20 1995 Data __SE. 215 017 004 024 006 004 AdjR7=.13 Hematocrit D value 0001 8 19 20 04 21 Parameter 46.61 020 0.04 031 002 006 R*=.10 1997 Data __SE p value 2.56 0001 020 3 004 38 027 26 007 7 004 a4 Adj R= 02] Intercept PFOS Age Alcohol BMI Cigarettes Parameter 17.00 002 001 0.002 006 0.003 RP=.18 1995 Data __SE 072 0.06 001 0.08 002 001 AdjR=.10] `Hemoglobin D value 0001 70 36 9% o1 19 Parameter 15.55 0.07 001 005 001 002 R'=.07 1997 Data __SE 088 007 001 009 002 001 ARd *= j 00 p value 0001 33 44 61 70 12 001164 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 5.21 0.002 -0.003 0.006 0.007 0.005 R*=.06 Table 14 (continued) 1995 Data RBC 1997 Data SE p value Parameter SE p value 022 0001 502 030 0001 0018 8 0.003 0.024 88 0.004 55 0.003 0.005 53 0025 81 0.025 0033 a4 0.007 28 0.004 0.008 64 0.004 18 0.005 0.004 28 AdjR?=.03 RP =.04 AdjR7=.04 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 3297 005 001 0.04 0.07 0.04 R'=.18 1995 Data MCH 1997 Data. SE D value Parameter __SE b value 125 0001 3113 143 0001 010 60 0.11 [or 31 002 61 0.004 0.024 85 014 79 0.06 0.15 mn 004 07 0.007 0039 36 002 06 007 002 00; AdjR?=.10 R*=.19 AdjR'=.12 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 33.55 0.03 001 0.08 0.02 0,02 R=.18 1995 Data MCHC 1997 Data SE p value Parameter __SE b value 053 0001 3340 050 0001 004 55 0.005 0039 8 001 20 0.005 0.008 55 006 18 0.10 005 07 002 a7 0.001 0014 92 00) o1 0003 0.007 69 AdjR*=.10 R'=.09 AdRj = 01 001165 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 98.33 009 -007 030 0.15 0,19 R'=27 Table 14 (continued) 1995 Data SE 359 029 007 040 oll 006 AdjR'= 20 b value 0001 6 34 45 18 003 Mev Parameter 92.85 0.28 0.02 0.19 -0.03 020 R'=.22 1997 Data __SE 382 030 006 041 ol 006 AdjR'=.15 D value 0001 34 6 65 8 0008. Intercept PFOS Age Alcohol BMI Cigarettes Parameter 295.55 3.96 084 -10.54 0.54 0.78 R'=.19 1995 Data Platelets 1997 Data SE p value Parameter SE D value 37.09 0001 392.12 4822 0001 296 19 384 373 31 071 24 231 081 006 413 ot 6.59 5.16 21 Liz 63 -185 133 a1 063 2 082 070 25 AdjR?= 11 R*=21 AdjR'=.14) Intercept PFOS Age Alcohol BMI Cigareties Parameter 3.10 003 0.002 007 0.10 0.12 Ri=43 1995 Data WBC 1997 Data. SE p value Parameter SE p value 119 ol 4.46 136 002 009 7 004 oll 70 0023 93 0.007 002 75 0.13 62 021 ols 15 004 007 0.06 004 0 002 0001 oll 002 0001 AdjR*= 38 R'=40 AdjR'= 34 001166 Table1s Employee Distribution sto Plant Locationand Whether Hormones Were Measured, 1995 pormo)s Tous [1rsT a m3e6x 3 7s BothLocations -- Arve Bviemin Decatur _YHeosmongsMNeaosured THeormenesMNeaoured _YHeormanesMesNsoured B0E@I AsERs) AIHE) BG0K7) B1E0%T) M00E1E%)) sNoTmH JSeWmE oBOeSmH ws % 0 i1o6Hw 3G0EsR) 3 E] 1wews)w % 28 5 3 Tasers MesPVatlefoLtPOnS,nDdeamoagr.HSoememsChweomeisWes srd Ho39g5s, BothLocations Antwerp Decatur. Hie Mem ow Be ow wn Mg PFOS 287 152 260TM 092 310" 1.96 Age 384" 271 350 384 429 459 aAlcohol 10" 04 16" 08 02 02 ws wr me we ws ms aonCigarettes. 83" 43 61" 19 103 woos om wes sm 60 ws FR EB owe wom ow ow ww > AlkalincPhosphatase 86 86 n 7" 9 9% cToameime16t) vane car ast ar ToBibn Dicebinbn Cosel wo oYNaesmiNtew aa n a= 07 os 02 02 0 ms wow HNYeeom maNw us n =u " us os 0 02 2 wm wm wm CNHheworVaNsetw 0 "0 a 5 us os as a 02 wow wm om 2 HDL 9 a8 2 Togheides 158 io 52 ES "a "a 3 104 205 1m v `Hematocrit 41 6 4 47 4% a5 Hemgain 1413 ase asa sas HoBmootnhLeoscaMteiaosnusred Varisble YNe=sS NNo=o0 RBC 50 49 men au 310 mete 0 353 Mev % 9 we 73" 6s PTpl<.a05cep<OL p2e.0001 2 (Tcoanbtiinu1e6d) HomoAnnetsweMrepasured YNeso NNoe ra 49 as 313 29 28 9% 9 68 57 a 21 HormoDneecastMuerasured YNesem NNoes 50 49 0s 08 32 ns 2 92 80 70 26 23 38 rR 3 Table 17 Mean, MeDdemioagnr(aMpehdi)c,,SStearnudamrCdhDeemviisattriioens (aSnDd)HoefmaMteoalongiacnadlRVaanlgueesof PFOS, for N = 88 Employees, Antwerp and Decatur Combined, who Had Hormone Measurements, 1995 PFOS (opm) MeanMed SD Range PFOS 0-<1 068' 075 021 037-090 1-<3 196' 196 062 1002.90 3-<6 415" 397 085 3.00-5.80 26 8F6a7l'ue8=50121.32,8p5= 0060.016-12.83 0-<1 Age 327 325 63 210430 1.<3 387 390 84 250-580 3-<6 390 390 76 260540 26 430 420 78 370560 Fvalue=24,p= 08 0-<1 14 ALlLcohol12 0036 1-<3 06 02 08 0036 3-<6 14 05 20 0060 26 09 00 13 0029 Fvalue=2.1, p=.11 0-<1 245 2B45MI 24 204280 1-<3 279 262 72 196.607 3-<6 47 242 42 179325 26 275 294 49 206330 Fvalue=2.1, p=.10 001171 PFOS (ppm) 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 >6 0-<1 1-<3 3-<6 26 Table17 (continued) Mean Med SD Cigarettes 60 00 105 7700 112 1L6 120 118 06 00 13 F=18, p=.16 Range 00250 00350 00-400 0030 170 B16U0N 31 140-220 158 150 38 80-260 170 170 38 100-230 144 140 40 100210 Fvalue=11,3p5= L01Cr0eatinin0e1 0811 1009 02 07-16 09 09 01 0712 LL 12 04 0616 Fualie=p2=70,5 2 G8lucose7 709 8 84 29 62260 8182 12 6612 87 83 16 71105 Fvalue=08, p= 52 Alkaline Phosphatase 82 82 14 66103 88 8 25 49.146 85 82 20 3202 88 74 29 63.136 Fualue=03, p= 84 001172 PFOS (ppm 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 Table17 (continued) Mean Med SD Range 38 2G8 GT 27 2311 S341 49 2203 939 1s 2180 48 49 19 279 Fvalue=09, p= 44 325AST23 17:9 0027 14 14% 235 24 6 1337 3130 4 2637 Fualie=p1=23,1 52 48ALT 21 36-108 48 43 24 25183 2 4 7 3059 5457 20 298 Fvalue=L1, p=.36 Total Bilirubin 086 070 045 0.40-200 067 065 028 020-130 065 060 031 020-L40 068 070 015 0500.90 Fualue=12, p=.30 0D2i2rec0t2B0ilir0ub0i4n 020030 020 020 005 010030 022020 004 020-030 022 020 004 020030 Fualue=06, p=63 001173 PFOS (ppm) 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 Table 17 (continued) Mean Med SD Range Cholesterol 213207 33 180-290 20 227 42 144315 27 214 29 171270 200 208 34 160-240 Fvalue =0.5,p= 69 129 1L28DL 22 106-177 136 146 39 65.228 139135 29 84.190 129 130 29 95472 Fvalue=03,p=.85 257HDL12 36 S046 15 2894 46 48 12 2374 4546 10 3461 Fvalue=06, p=_64 1577 Trig1l2y1cerid1e6s7 41-622 163 129 118 41.651 156 138 97 34.413 128 151 52 64-187 Fvalue=0.1,9p4= Hematocrit 4748 2 4449 46 46 3 3952 a7 41 2 Bs 47 48 1 4549 Fvalue=23, p= 08 001174 PFOS (pm) 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 >6 0-<1 1-<3 3-<6 26 Table 17 (continued) MeanMedSD Range 156 Hem1o5g8lob0in5 146161 152 153 09 130-17.1 156 156 07 138174 155 154 07 148.162 Falue=18,p=.16 49 5R0BC 03 4352 49 49 03 4357 50 50 02 4654 50 52 07 4057 Fvalue=04, p=.74 320 3M1C7 H LI 308339 308 308 14 273332 312 318 Ls 260.333 31302 34 282.369 Fualue=19, p=.14 329 MCHC 331 08 319345 330 31 07 317345 329 328 07 313342 31333 08 322340 Fualie=02, p=.93 97 9M5ev. 5 92106 93 93 4 8ni0l 95 95 5 8I-104 9 91 12 sss Fualue=19, p=.13 001175 Table 17 PFOS (continued) (ppm) Mean Med SD Range WBC 0-<1 67 65 18 44.94 1-<3 7369 22 3615S 3-<6 7775 23 41133 26 7169 06 6478 Fvalue=07, p=.59 Platelets 0-<1 243230 43 189-300 1-<3 3-<6 234 227 44 153365 29 230 50 132344 26 77182 29 143.205 Fvalue=27, p=05 1. 2. Significantly different Significantly different (p < 05) than (p <.05) than the remaining three PFOS exposure the 0- < | ppm PFOS category. categories. 3. 4. Significantly Significantly different (p <.05) different (p <.05) than than the the 1 3 - <3 <6 ppm ppm PFOS PFOS category. category. 5. Significantly different (p < 05) than the > 6ppm PFOS category. `Sample sizes: PEOS Level 0-<Ippm 1-<3 ppm 3-<6 ppm >6ppm Both Locations 10 46 2 s 88 Antwerp 9 21 18 520 Decatur 1 2 9 338 001176 Table 18 MultiivnaRreilaabtlieoRnetgorePsFsOioSnAodfjSusetriunmg CfhoremAigset,riAelscoahnodl,HeBmMatIolaongdiCciaglarPeatrtaems,eters Antwerp `aWnhdoDHecaadtuHrorDamtoanCeoMmebaisnuerde,mFeonrtsThions1e99E5mployees Varigble Intercept PFOS Age Alcohol BMI Cigarettes Alkaline Phosphatase Parameter 64.57 0.002 013 4.17 0.60 0.60 R'=22 SE D value 1523 001 Lil 99 030 66 175 02 039 13 020 004 AdR=.17 Variable Intercept PFOS Age Alcohol BMI igarettes InGGT Parameter 1.9570 0.0077 00157 0.1043 00341 0.0096. R*=.20 SE 04203 0.0301 0.0084 0.0484 00107 0.0056. AdjR?=.15 p value 0001 80 07 03 002 0 Variable Intercept PFOS Age Alcohol BMI Cigarettes AST Parameter 16.13 0.13 0.006 1.02 051 020 R?=.08 SE value 9.90 1 7 86 020 98 114 3 025 04 013 a3 Adj R?=.02 001177 Variable Intercept PFOS Age Alcohol BMI Cigarettes Table 18 (continued) ALT Parameter 25.19 0.12 -0.04 020 095 020 R*=.10 SE 1422 104 028 164 036 019 AdjR'=.04 p value 08 90 89 90 ol 29 Variable Intercept PFOS, PFOS? Age Alcohol BMI Cigarettes In Total Bilirubin Parameter 0.6133 00885 0.0073 00025 0.0235 00270 00162 R'=39 SE 02726 00518 0.0048 00054 0.0309 0.0068 0.0036 AdjR= 34 p value 03 09 13 64 45 0002 000) Variable Intercept PFOS Age Alcohol BMI Cigarettes Parameter SE. D value 0.225 0.0335 0001 0.001 0.002 64 0.0007 0.0007 31 0.004 0.004 26 0.002 0.0009 005 0.0003 ___ 0.0004. 44 R*=.09 Adi R*=.03 001178 Table 18 (continued) Variable Intercept PFOS Age Alcohol BMI Cigarettes BUN Parameter 1873 0.10 -0.05 037 0.003 0.05 R?=.08 SE 272 020 005 031 007 004 AdjR*=.02 D value 0001 60 35 24 97 14 Variable Intercept PFOS PFOS? Age Alcohol BMI Cigarettes Creatinine Parameter 0.5031 00488 0.0051 0.0086 00119 0.0090 -00017 R*=.37 SE 0.1178 00223 00020 00023 00133 0.0029 00016 AdjR'=32 p value 0001 03 01 0004 38 003 28 Variable Intercept PFOS Age Alcohol BMI Cigarettes IGnlucose Parameter 3.8241 00029 0.0051 -00052 0.0166 0.0018 R'=.42 SE. 0.1090 00079 00022 00125 0.0028 0.0014. Adj R=* 38, p value 0001 a1 02 68 0001 2 001179 Table 18 (continued) Variable Intercept PFOS Age Alcohol BMI Cigarettes Cholesterol Parameter 198.04. 283 126 132 073 007 R?=.09 SE 26.88 197 054 309 0.68 035 AdjR*=.03 D value 20001 15 02 67 29 85 Varisble Intercept PFOS Age Alcohol BMI Cigarettes LDL Parameter 152.37 045 070 5.58 -L19 -059 R'=.14 SE 23.90 174 048 275 061 032 AdjR*= 08 value 20001 80 14 05 05 07 Variable Intercept PFOS Age Alcohol BMI Cigarettes HDL Parameter 77.68 0.66 031 2.68 066 007 R'=32 SE 8.51 062 017 098 022 ol AdjR7=.28 value 0001 29 07 008 003 56 001180 Variable Intercept PFOS Age Alcohol BMI Cigarettes Table 18 (continued) Triglycerides Parameter 17852 789 422 9.90 607 3.17 R'=32 SE 7197 526 144 828 183 095 AdjR'=28 D value 02 14 005 24 001 001 Hematocrit Varisble Parameter Intercept 48.03 PFOS 0.05 Age 0.02 Alcohol ~~ -0.003 BMI 0.10 Cigarettes 0.04 R'=.12 SE p value 1.66 0001 or 0 003 48 0.19 9 004 0 002 05 Adj R= 06 Variable Intercept PFOS Age Alcohol BMI Cigarettes Hemoglobin Parameter SE 15.76 0.58 002 0.04 0.04 007 001 001 -003 001 0.009 0008 R?=.09 D value 0001 67 28 58 03 25 AdjR*=.03 001181 Variable Intercept PFOS Age Alcohol BMI Cigarettes Table 18 (continued) MCH Parameter SE 33.52 105 004 008 0.006 002 0.11 012 0.10 003 003 001 Ri=24 D value 0001 59 79 35 0003 03 AdjR?=.20] Variable Intercept PFOS Age Alcohol BMI Cigarettes MCHC Parameter 32.87 -0001 0.008 -008 00006 0,01 R=.07 SE 0.50 037 001 0.06 001 0007 AdjR'=.02 p value 0001 98 42 19 96 008 Variable Intercept PFOS Age Alcohol BMI Cigarettes Mcv Parameter 10197 0.14 0.04 0.56 -031 0.12 R'=28 SE 3.36 025 007 039 009 004 AdjR'=.23 p value 0001 56 53 15 0005 0007 001182 Table 13 (continued) Variable Intercept PFOS Age Alcohol BMI Cigarettes RBC Parameter 4.673 0.009 0.005 0.026 0.006 0,002 R'=.08 SE 0214 0016 0.004 0025 0.005 0.003 AdjR?=.02 p value 10001 58 28 29 24 48 Variable Intercept PFOS Age Alcohol BMI Cigareties Variable Intercept PFOS. Age Alcohol BMI Cigareties Platelets. Parameter 320.83 673 0.94 695 -126 0.43 R*=.18 SE 3221 236 0.64 3.70 082 043 AdjR?=.13 p value 0001 006 1s 06 13 32 WBC Parameter 3.24 -003 007 0.03 003 0.09 R'=35 SE p value 132 02 0.10 74 003 01 0.15 82 003 42 002 0001 AdjR*= 31 001183 Table 19 `HormMoenaaln,MeMaesduiraenme(Mnetds)f,orStNan=da8r8dEDmepvlioatyieoens,(SADn)twoefrMpeaanndaDnedcaRtaunrgCeoomfbiPnFeOdS,, 1995 PFOS (ppm) Mean Med SD Range 0-<1 193 C1o7rt5isol7.0290 1-<3 177 180 72 10420 3-<6 204 230 72 70310 26 170 190 62 9.0230 F=17,p=.18 0-<1 1-<3 3-<6 26 DHEA-S 388% 358 168 2424210 95 316 318 106 F1=9843,p1=90.000119 88-605 69460 90-530 176-215 0-<1 67.1 E6st7r0adiol128 500-87.0 1-<3 603 590 152 350-10.0 3-<6 60.5 610 101 4208.0 26 648 650 187 470.920 F=08,p=.49 0-<1 38 3E5SH 15 2060 1-<3 56 40 42 10260 3-<6 56 40 39 20180 26 66 60 34 30120 Falue=08,p=0.48 17-Hydroxyprogesterone 0-<1 1-<3 170 164 41 121245 Bl 123 52 53204 3-<6 150 153 52 65-245 >6 19 98 4590-197 Fvalue =2.4,p= 08 001184 PFOS (ppm) 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 0-<1 1-<3 3-<6 26 Table 19 (continued) Mean Med SD Range 38 40LH 09 2050 46 40 30 10210 46 50 19 2090 48 50 13 3060 Fvalue=03, p= 81 135 Pr1o3l0actin70 60290 118 110 50 30300 134100 79 50390 136 100 63 9.0240 Fvalue=p0=56,7 SHBG 09 09 03 0513 10 09 04 0419 10 09 03 0417 12 13 06 0621 F=1lp=35 Freetestosterone 205 202 52 102282 162 161 33 8927.1 177 182 32 122252 175 177 20 153205 Fal=4u.5,ep= 006 Boundtestosterone: 739 757 175 5281094 580% 589 110 278-762 676 659 171 410-1039 T7216 462-883 Falue =52, p=.003 001185 Table 19 (continued) PFOS (ppm) Mean Med SD Range 0-<1 19 1T4SH 13 0645 1-<3 10 15 14 0581 3-<6 Is 14 08 0534 26 20 16 12 0738 Fualie=06, p= 62 Sample sizes: POS Level 0-<Ippm Both Locations ___ Antwerp __ Decatur 10 9 1 1-<3ppm 46 21 25 3-<6ppm 27 18 9 26ppm 838 320 338 001186 Table 20 MultivariabAldejuRsetgirnegssfoironAgAen,alAylscioshoolf,HBoMrImoannedsCiignaRreetltaetsi,on to PFOS Antwerp and Decatur Data Combined, 1995 Varigble Intercept PFOS Age Alcohol BMI Cigarettes Cortisol Parameter 27.13 027 0.10 1.56 -025 0.01 R'=22 SE 484 035 0.10 0.56 012 0.06 AdR'=.17 p value 0001 4s 31 006 04 81 Varigble Intercept PFOS Age Alcohol BMI Cigarettes DHEAS Parameter 499.17 295 530 17.8 -182 225 R'=28 SE p value 76.98 10001 563 60 154 0009 8.84 05 195 35 101 03 AdiR=2 Variable Intercept PFOS PFOS Age Alcohol BMI Cigarettes Estradiol Parameter 53.56 382 0.44 0.13 2.42 057 0,07 Ri=18 SE 9.76 185 0.17 019 1.10 024 013 AdjR'=.12] p value 0001 04 01 S51 03 0 58 001187 Table 20 (continued) Estradiol (without employeCe) Variable Intercept PFOS PFOS? Age Alcohol BMI Cigarettes Parameter 53.43 356 040 0.13 2.43 056 0.69 R*=.13 SE 9.84 239 028 0.19 Li 025 013 Adj R=.06 p value 0001 4 a5 1 03 03 60 Variable Intercept PFOS Age Alcohol BMI Cigarettes ESH Parameter 3.64 002 0.14 004 0.13 0.005 R*=.10 SE 279 020 006 032 007 004 Adj R=* 05, p value 20 91 0 89 07 90 17-Hydroxyprogesterone: Variable Intercept PFOS Age Alcohol BMI Cigarettes Parameter SE p value 306.10 3269 0001 004 236 99 2.13 067 002 0.76 3.68 84 347 082 0001 0.79 042 01 R'=33 AdjR'=.28 001188 Variable Intercept PFOS Age Alcohol BMI Cigarettes Table 20 (continued) LH Parameter 565 00s 0.02 0.24 0.03 0,03 R=.04 SE 186 013 0.04 021 005 002 AdjR?=.02 pvalue 003 69 69 26 56 21 Prolactin Variable Intercept PFOS Age Alcohol BMI Cigarettes Parameter 16.67 034 0.15 175 0.004 0.14. R*=31 SE 399 029 008 046 0.10 005 Adj R?= 27 value 0001 25 07 0003 97 01 Varigble Intercept PFOS Age Alcohol BMI Cigarettes SHBG Parameter 0.03 0.005 002 0.005 0.005 0.004 R=28 SE 024 002 0005 003 0.006 0.003 Adj R*= 23 D value 89 7 0001 86 40 19 001189 Variable Intercept PFOS. Age Alcohol BMI Cigarettes Varigble Intercept PFOS. Age Alcohol BMI Cigarettes Table 20 (continued) FTreestosterone Parameter 27.37 0.02 0.14 0.11 -0.19 0,01 R*=.19 SE 2.57 019 005 030 0.06 003 AdjR'= 14 Bound Testosterone Parameter 993.88 691 243 7.41 -1143 1.22 R'=28 SE 10093 7.28 206 1137 252 13 AdR'=23 value 0001 90 o 69 005 68 p value 0001 35 24 52 0001 3s Varigble Inercept PFOS Age Alcohol BMI Cigareties TSH Parameter 0.873 0.004 0.003 0.078 0.096 0,011 RP=23 SE 0.826 0.060 0016 0.095 0.021 0011 AdjR*=.18 D value 29 95 85 4 0001 32 001130 e1cuR1e Scatter Plot of Estradiol and PROS, Both Estado Locations PROS Combined, 1995 Toc ; 100 000 : | | 90000 ; 80.000 vr, 700 4 LT] . 60.000 mos -- soo 4 7 TLe T .Tae 40.000 30000 000 ?. J - 2000 4000 600p0ros8000 10000 12000 16000 -- Unease =PolynFoitdmegireae=l2 Estradiol = 66.47P63o-3l,6y04n4Foi8tPmdFeigOrSaee+l=02.42167 PROSZ Asquare `summoafrFyit Square Adj o0d.s0u76z1a6 MFooaotnMoefaRnoSeapuoarreesEro S1333369144 Observations (orSumWgts) 8 ESNomoudrrcae Cow TInPatramoresagt Prose OF2 SAumcniSaoufaVsairsiasnce MeamSqws 1245701 ies 3rasto aa7 1185315180346843 IT poraatbst SsdErsP0atraaartmeeeterESxSiUmEEatmEers (1Raao Psrooboonnl caaisseanz 016T7r70e5 32s%: GSooreey 001191 Estradiol +59.7222 + 0 57198 PFOS Asquare Summary of it RSquare Adj 000.000471335 MReooatnMoafaRnesSpqounasree ror `Observations (or Sum Wats) 6113.734603167 a MSooduerlce EmCoTrota ITnotemrcept PFOS OF1 Analysis of Vadance SumofS1q2u0a2r2e6s Mea1n2S0q2u2a6e F0R6a3t6i8o 82 1612633658.316348 188792 P0r4o2b7o1F ParameterEstimates 59E7s2t2im2a3t6e 05719843 2S50E50M93 0716766 2t3R6m5o <Proooba0p 080 Gari 001192 e1aRe 2 Scatter Plot of Estcadiol EaunadsoPiROgSy,prBoosth LocWaittihoonustCoEnnipnlboeed,s A1995 T0000 100000 . so000 | woo | LAT i momo aLtifeelr 0000 | TNA .. soo {L2 h0e,Seal "000 EBAe 0.000 000 2000 4000 600P0ros8000 10090 12000 14060 --PolynoFitmdeigraoeln2 -- neaFrt Estradiol =65.86P20o-3l.1y05n6Foi3tdPmoFgiOrSea+e=l0z.4755 PFOSY2 Asquare SummaofrFyit RquareAd] 0"002000825727 OFbMosaoeartnvMaeotfaiRnoenSssqpuo(aonrrseSeuEmrWoarts s1130.1410421957 ESNroooudrracle Tow TIFnotFmoOcSapt PROS? OoF2 SAumnoafSloufyVsassdaincse MeanSqure 15s08l0o3g49 T1508634270 P0r8FoAeanrteso a 15408985 o4ts0 EsPtairmaamtaeterEsStwinEartoosr 0e331sT0s5ea6T9t23 o42oz37m4eei9ii1az t14h8s137e Po'a<rob00o7e9y) 13s 0218) 001193 Une Fi Estado 620271 - 0 26861 PFOS. Summary of Fit ASSqquuaarree Adj MReoaonMofeaRnesSpqounasree Error Observations (or Sum Wats) 0-.00.0020395386 61130414174397 I MSooduerclo TEmootral Analysiosf Variance O8sF1 SumofSq3u6a.r2e9s5 15370504 MeanS3q6u2a9r5e F0.R2a0t0i7o 180832 ProbaF 86 15406.989 0.6553 InTtoemrcept PROS ParameterEstimates 620E2s7t0a6t0e 2S68U8E48m8 0368607 0822768 2t3R0a5o P<roo0b0s1t 045 06583 001194 APPENDIX A `Total Bilirubin and PFOS Scatter Plots DRAFT 001195 Seatac Plot of Total 8ilicubin and F605, Both Locations Compined, 1955 rE 2% ww] fad oo A10 Sov" Ne a . a : oo 2m 4% ihrosom rob mh wh JiE -- m To S0on7nsamn arrozei epcs nsaune BREST queaErenAdSS jameee espe o0F.301r6ima69e2 G BSmoO alOF a[ mSSmamomt-- smmm MeMTmeisnmsaaewwdss aruonem fTBioemw oCSufonna oSEnaawmms tmanwee Prouuonn To Stns = 0P4o55eS3m0orrasoopgrunoss one rz 001196 ARSSaqquuaarree Adj RMoaoatnMoefaRnesSpqounasree Error `Observations (or Sum Wats) 00008410677743 00731589604089 7 Analysis of Variance MSooduerlce Emo OF2 174 Sumo1f2S2q2u0a0s6s 22426468 Me0an6S1q1ua0r3e F4.7Ra4t0i8o 0128888 Prob>F C Tot 176 23648475 0.0088 InTtoemrcept PPFROOSS'? Parameter Esimates 0E86i5n31e8 0S0W5E4m7o48r 000000814852) 000033380442 R15a8o1 P<roo00b1 22937 000020144 001197 Scattec Plot ofTToostaB l Biil8icPunbFiOnS and pos, Antwecp, 1995 oT 20 | aw. f.1 2 ant . 0 rt 5 2 soi TL 200 4% 6mPros sw 100 re remo pur --PolynoFimdeigraeol=2 TotaBibi U0n92e0a0r1Ft~0.02927 PROS RBssaquuaarree Adj SummarFyt Gc0oormraesss ChRMsoaoeatrnvaoeftaoSnunSssqpuo(aorrreSesuEmrWorot) Hodoreeras oSesures OF7 SAumonloSasomfarVeyasstasrce MeDmaSwmwse oFreasc a dime ole meme Ta 145s Sates FTiPormmoasapt osCioaPacmroaammsseterEcsSiomumteerss R`easos Prromv sme cose GB sme Tos Brun 0P.o96-t05r.04F7oi887dm2egPraeFolnSz 0.00697 PFOS2 SummaotrFye 001198 SASqquuaarree Ad) MRosoatnMoefaRnesSpqounasree Error Observations (or Sum Wats) 00000247652035 00846037663365 a MSooudracle. ETrootra nTtoomrospt PPFROOSS'2 Analysis of Variance O8F2 Sumo0f3S9q8u4a7e0s 14124166 Me0a1n9S0q7u3a5e 1F.R2a0t2i0o 0166167 ProbsF &7 14520636 0.3086 Parameter Estimates 09E6s4tm7s8i9e 0S0U7E9m7o9r 00000T6B9T7I409 00000578556685 1t2R1a0o P<r0ob0a0i1| 103924 0031580235 001199 Ee 2 20 foe . Tdi of ---- om 20 6 emosew wk ah ee --"irrises ToSaos smarmraeet rcusi108 . EEA RsEaEmgeLLe re sporgandudnr2s ofSESwoOoF8 SfoisEnsmiamosmvsmata NeaMwsseawdse ocFrana vai EHonSo oSPoSamare cmSmaiainmn numme proen ToBusa ipnteiprsosossterosws Roque ocsses 001200 AFoSoqtuaMreeanAgS)quare Error MObesaenrvoaftiRoensspo(onrsSeum Wats) 00021407056058 05752881 MSooduercle ECrTmootral Analysis of Variance O6F2 Sum0o.i7S7q2u2a6e2s 52680018 Me0a.n0S8q8u6w13e F1R.a4t46i5o 0061260 ProbsF 88 54456180 02611 InTtoemrcept PFPORSO'S. Parameter Estimates 0.E6s6t7i4ma1t8e 0S0W63E2m5r8 0000051887323 00000334258311 1t0Ra5i9o Pr<o0b00s1t 117508 00..10187298 001201 Scattac Plot of Total Bilicubin and PROS, Both Locations Combined, 1997 Tou Bu8n1PRnOS = 2 150 3i 0 If: r . : os frmim Ta To TM 20 40 em so 10% rz pros or -- PotpFotdnogriee=l2 Total Bobi 0r718e5 002583 PFO RAesluesa SommayeFlt ooooroesziaats e aJmvTesSum Wie fpereTra : =oSoourhce Fa aOF7 18 ASnuamloySsla iSisaowmfmVeearsiance MeoUmwsSweewnss EHH eSFreniso Soe oTeommsen oSru[ iang -- oSbeEn tihssee PFeoemd Gos couse 18 5 ToaBilbin = 0[ 76983 r 0.048p PROS 0.012 PEON nsRquarae SummaorfFyt aaoousrae 001202 MRoeoatnMoefaRneSsqpuoanrses Error Observations (or Sum Was) 00351782298713 148 NSooduarlce ECrootra Analysis of Variance 14O5F2 Sumo0i.S7q0u4a7e87s 14687105 Mea0n3S5q2u3w8r3e 0101200 3.F4R7a9t0o ProboF 147 15391892 0.0: InTtoormcopt PRPFOOSS ? Parameter Estimates 07E8s0t6n2g6t4e 0104564 0S0W5E1m4o9r 0040828 R1a53o4 257 Pr<o0b0o1f 00111 00120040 0005663 242 0037 001203 Scattec PIO of Total Bilicubin and POS, Antwecp. 1997 Tow BunoybROnS I 200 51% i Ew Re Se 0s 20 40pros em am 10 near --PopFrodegrele=2 Tota Bint = n08e51a7r- 0.03847 PFOS RmsSqrureoAg SummaortFyu opouraser FGoHhaosaatrnviastFohonsSspaou(oanrrsSyuEmWrart) QG7oaaear"ss EoGrohce OaF7 sr umoatrSiua-- eeos MeMaUnRsR SHED Crass PCFoehearsso Tow & oSasarso a3 PJ Truoms osP sPaireamsore R sciomroens hi -- al Doser Gomer 0% se Total Bf 0.P963o5 r0a.2F2tr84d7sePgaReOnlS + 0.0482PROS" RAsoqquuaeroAdi SummaortFyu oGeozsatreers 001204 MRoeoatnMoefaRnesSpqounasree Error Observations (or Sum Wats) 00637r2az96713 148 MSooduerlce Analysiosf Variance OF2 Sumo0l.S7q0u4i7e8s7 Mo0an3S5q2u3a8r3e 3R.4a79o0 ECroorta 141457 1154369817819025 0101280 P0ro0bs%F iTntoomroopt PPRFOOS Parameter Estimates 07E8s0t6n2g8t4a 0104584 0S0W8E1m4o0r 0040825 (1R5a34o 257 Pr0o0ba0t1y 00111 0012040 0.005663 212 00387 001205 Scattec Plot of Total Bilicubin and PROS, Antwecp, 1997 Total Bunn By PFOS. 250 200 FREY 2I ---- 050 00 200 400 600 800 1000 Pros -- near Fit ---- Polynomial Fit dogroe=2 Unear Fit "Total Bliubin = 0.851-7 0.03647 PFOS `Summary of Ft RSSqquuaarree Adj Root Mean Square Error 000.1040219611 0.385334 `MOobasenrvoaftRieosnspo(nosreS.um Wats) 0.7968a75 MSooduercle. EmCootra Analysiosf Vadance O62F1 Sumo0f.S1q3u4a6r7e0s 92050080 Moa0n.S1q3u4a6r7e 0F.R8a0t8i9o 0148482 ProboF & 5:33%3750 0.3468 InTtoemrospt PFOS Paramate Estimates 08E5s1t6i9ma9t0e 0S0U75E2o5r9 003474 0038471 1t1Aa3t2o P<r0o0b0s1i 095 03468 PolynomialFitdegree=2 "Total Bilirubin = 0.9635 - 0.22847 PFOS + 0.0462 PFOSA2 Summaroyf Fit ASRqSquuaarree Ad] o0.00s2t0e7a61s 001206 RMoeoatnMoefaRneSsqpuaanrseeError Observations (or Sum Wats) 00.378916080775 C3 MSooduerlce ETrootral InTtoermcept PrPFoOsS ? Analysis of Variance OotF2 Sumo0f.S4q8u4a2r5e5s 88551485 Me0an2S4q2u1i1r3e F1R.a6t7i8o 0145165 Probar & 3.335750 0.871 Parameter Estimates 0E9s6t3m6e0l1e 01S0W3E4m0o2r o0o2d2e8i4es8t6 0o1o229s273i8a t9R3a1o <P0r0o0b1a 117557 00..10822513 001207 Scatter Plot of Total Bilirubin and PFOS, Decatur, 1997 Total Bkrubin By PFOS 250 200 1.50 3 10 0".00 FE 00 200 400 PROS 600 800 1000 : -- Linear Fit ---- PolynomialFitdegree=2 Unear Fit "Total Bifubin = 0.59609 ~0,00884 PFOS `Summary of Fit RRSSqquuaarree Adj 0-.00.0004792214 MRoaoatnMoefaRnesSpqounasree. Error 0.5708.527210 `Observations (or Sum Wats) a MSoodurecle EnCmTootral Analysia of Varance DF1 82 Sum0o0f2S1q2u7a7e5s 43001510 Me0a0n2S1q2u7w8e 0052441 0.F4R0a5t7o Prob>F 8 43214206 0.5259 TInotrorncopt PFOS. Parameter Estimates 05E9s6t0m8a2t6e S0.W03E7r1o61r 0.00837 001403 1t6R.a0t4o P<r.o0b0s0f1) -064 0.5250 Polynomial Fit degree `Total Bifrubin = 0.68287 - 0.09408 PFOS + 0.01143 PFOS*2 `Summary of Fit ARSSqquuaarree Adj 00..004781447075 001208 MRoeoatnMoefaRnesSpqounasree Error `Observations (or Sum Wats) 0os272s2s57718 a NSooduarlce ETrortal Tinotemrcept PRPOFSOS2 Analysis of Variance O81F2 Sum0o.f3S0q8u7a3e4s 40128552 MeoaniSsquiieo 3.F1R1a4i3o 0043541 ProboF & 43214286 0.0458 Parametor Estimates 08E8s2tm8s7t6e 0S0W5E1T02r 00000141048226 00000347784056 1t3R3s8o 243 P<u0b00s1 00151 241 00183 001209 eroue 1 Scatter Plot of Estradiol and PFOS, Both Locations Combined, 1995 rr . Cons 705 |7 100 000 | 90000 ; woo| ve. woo wnt] - EE somo D13 h0 Fue ow FIT 200 00 200 40 000 sao fae 12m tas Pros ----UPnowtrtpoFrndeigraele . Exact 60.47P00 e6r34F8oidPeRngOrSeie+0.42197 PROSE iRmsquar)s summa ott oagieers NRaSoaotneMaeannSgquooarreemErrWoron ane] 13.33914 RSoeuhe ow ibTasom w Prove OF2 sJumooihswotywsVessarsce Fi MeMmseuwde fFroaes Hau ait aGo[ inna -- cSomEm San Othe nv4se%o Poy sa ome climes 1% cum 001210 Estradiol 59.7222 +0 57198 PFOS Summary of Fit ARsSaquuaarree Ag) Foot Mean Square Error 00.0000743195 1374017 OMbesaonrvoaftRoensspo(onrsSeum Wats) 51.359868 SMooudrecle ECnoTrou TInotomrcopt PROS Analysis of Variance O8F 1 Sumof1Sq2u0i2r2e6s 162368.138 Mea1n2S0q2u2w6e 0.FR6a3i8o 188782 Prob>F o7 16358384 04271 Parameter Estimates 59E7s2tn2s2t3e 25S2W5E0m9o3r 05719843 0716765 R23a6o5 Pr<o0b00o1f 080 oa2ri 001211 erae 2 Scatter Plot of Estradiol and PROS, Both Locations Cominbed, 1995 000 Esuadol By PFOS Without Employee A 100000 . sooo | 20.000 Lo 000 o 21. . 000 a Te oo0 o 41377 S7y et] 40.000 30000 000 ts 2000 4000 6000 8000 Pros 10000 12000 14.000 --PolynFotmdeigraeelz -- UneFt `Estrachol =65.88P20o3.l10m6F6io0tPdneOgrSieel+=z034755 PROSN2 RSSqquuaarreeAdj `SummoafrFyit Foot MeanSquareEmor 00.00020287572 13.40325 MOobsaernvoaftiRoensspo(onr sSeumWots) eto114as MSoodurecre ErCoar Tnotamrcopt PPrrooss? O2F a AnaofyVasdansce Sunoi3S1q6u8e3s 15030348 Mew1n8S8e3u2w0e cFeReutro 5 15408380 179847 P0r4otvso0f Paramete Extmates 6S5lE8sot6is7nst1e 42o3Sr4ueEl9mi1zr 03772 ozmena A11s61mo7 Pocrorobeoopvny 13 orm 001212 SEIReE, SiE W5 BfrmoE4Gwor a-- mEammEEam MeTeesEns =oronme CBpmogw oe Prree mtne Ee ue em 001213 APPENDIX B Unconjugated Bilirubin and PFOS Scatter Plots PRATT 001214 IT) Scattec Plot of Unconjugated Bilicubin and PROS, Both Locations Combined, Unconpugated bikrubin By PFOS 1995 254 20 i 1s . bs at. os Toa * wide 200 4 60Prosso 1000 1200 1400 --liPneoalr oFtndogieea-2 Unconlgated ibnUn= o05wi6t657 0.0285 oS ARsqSuasreAd SummofaFt aodcraeustes HGooisaoenniovfaaoBnnSasaqorrrsSuEmrWres aGsoe5ztrisd EoSroyr Rw 17O3F| 1% SAumnooafoisleiowsfayeVssasssroiiansce MeOnDlasvdueewsres ime hLFaorsmoaEo Sere PWTruaomsce osEePkiaTneneso EOsSi0unwEsrmensr taasos Poobl "omen Oo em seem Uncoated ilsinP=om08o5r2i9e900d9g0r4e1a-F2OS + 0.00888 PROS'2 RAesqduaaread SummaofrFye aGsoslaessie 001215 HGRooasoaetnnMvoeafatRonenSssqpuo(aonrrsSeeurmaWror) oa33so2asonensz VSEoudrcas OF2 SAumoni(SasuSmvemyasrasnco Me"mTsewvewss aErsste ie hike Chien Pest Claw ire wasies Goce FTbuaomcson 0sL sPamreamdetery Estoiosmoartseys 3s aes Doosics Oana 331 door Prose oer Gomme se Gone 001216 Scatter Plot of Unconjugated Bilicubin and PROS, Antwerp, 1995 Unconsugaied bint By PFS 0 2s i 20 1s : 10 os 00 200 400 60 800 1000 1200 Pros --UnearFt ----Potynonial Frdegreo=2 UncoinlijUn=e0au.r6i0tg47a0.t0260e4PFdOS AAsSqquuaarreeAd `SummoafrFye oa0o0tssees1y7 FoMOhooeatanroMvfeatsRohonSaspaou(roaarSseuEmroWre) aO3s7k4aetrs4 ESMoroudrrece OF5 SAunoniO2S0uoufaaiVezassdasrceMeOmSzqwue Frarsaas a 2027s Ole Prober Cow & 12277150 0258 Tntoemespx osEssPuiusrnsaumseataEOsStU0Eateess t1h2a0o Pxroobusldg Fos ozs ooaisrs ia oss PotroFindeigraeel=2 Unconjugated bilirubin Asquure = 0.Su7m3-m09a.o01rf7F4y96u8 PF+0O .00S 686 o0zmrs PFOS*2 RSquareAdi 0oaiass 001217 MeRoaontoMfeaRnesSpqounasree Error `Observations (or Sum Wats) 00534744371388 5 MSooudrecle ECroTortal Analysiosf Variance OF2 8s Sumol0S3q4u0a8r9e4s 1.836165 Mo0a1n7S0q4u5a7e 1R.2a14o1 0140425 Prob>F 7 12277159 03021 iTntoomrospt PFPORSO'S? Parameter Estimates 07E3s0t1im9a2t3e 007678 S0W0E7T33r 0083838 t1R0a0l8o 139 P<r0o00b1 0.1800 00068606 0.00697 090 03268 001218 = w i" fFLoes:: . ToE h ehSreb wh hh roeomrs repn srree Ef BB Eem.t Re EA przo7d BAEEYo0r ertTiisemgmaavuvsemmsm o=ormwe BrBoea JSSEuEmeIsrNEseEr nRmeyoErmoo r sos p opa esreacsss eastetros 001219 "RRoSoqtuaMreeanAdS)quare Error `MOebasenrvoaftRioensspo(onrsSeum Wats) 00022351327418 0.3696863 SMooudralco ECroTortal ITntoermcept PRPROOSS}? Analysis of Variance O2F 86 Suno0f2S4q3u0a4e18s 45987481 Me0a1n2S6q6u7a1e F2R33a1t4o 00574 ProbF 88 48480809 0.1033 Parameter Estimates 04Es8t9im1at7e 0060663 0S0W5E6m1o02r 0032262 th8.a1i7 218 P<roob0o0f 0.0808 00060438 0003068 167 0.0817 001220 = - 5s. fof: HI [rhe w Tsoan mrsn 2 swarriGtrsm sasuragz ERHiaE., bc2s EF Z2E O" 7 B AnaUlofyEV' asdiianscee SUE rXIZD r3m, S L Fie tE e Y evensst Sraarpi comross ro `SummaryofFit so 01221 FAosoqtuaMreeanAdSyquare Error OMbesaenrvoaftiRoensspo(onrsSeum Wats) 0207.043220417 0543214438 MSooduercle EnoTortal Analysis of Variance DF2 Sumof0S5q2u1a2r8e4s Mo0a2nS6q0u8a2e 3F.R4a6t8i6o 114457 11.0432031294539 0075185 P0r.o0b33>8F iTntoemrcept PFPrOOSS.R2 Parameter Estimates 06E4s2ti7m1at3e 0S0U44E3m8r1 000010010378448 0000034580710 t1R4a4o8 Pr<0o0b0l1 226215 00.00120600 001222 Scattec Plot of Unconjugated Bilicubin and PFOS, Antwecp, 1997 Unconngated binubin By PFOS 25 20 5 1s 10 ! os St 00 200 4 pros 600 800 1000 -- Linear Fit ---- Polynomial Fit degroe=2 near Fit Unconjugated bifubin = 0.69161 -- 0.02872 PFOS. `Summaroyf Ft RSRSqquuaarreeAd) 00.0010231776 RMoeoatnMoefaRneSsqpuoanrseeError 00..362498145318 `Observations (or Sum Wats) & MSooduerlce ETrootral Analysiosf Vasance DF1 Sumo0i0S8q2u7a5e2s0 MecanoSequrr?e 0F7R6a3t8o 6&2 6677910780493177 0108340 P0r.o38b5>5F InTtoemrcept PFOS. Parameter Estimates 06E9s1t6im0a7t3e 0S0U8E4m2o88r `002672 00362 1t0R7a6o Pr<0o0b0l1 087 03855 PolynomialFit degroes2 Unconjugated bilirubin = 0.76708 - 0.19268 PFOS + 0.03045 PFOSA2 Asquare `Summary of it 0.040788 ASquare Adj 0.018634 001223 `MROoeboastanrMvoaeftaRinoensSspqo(uonarsrSeeuEmrrWoarts) 006342854435588 MSooduercle CEmoort InTtoermcept PFPORSOS' Analysis of Variance O61F2 Sum0o.l3S3q8u55a4e0s 64812807 Me0a1n6S9q2u7w7e 010523 1F5R9a8l1o ProboF & 7508437 02106 Parameter Estimates 07E8s7t0i8ma3t2e 0S0U8E8m4o0r3 00013942460777 00.0112088885 t8R5a0o <Pr0oba!f] 1-15755 00..10285640 001224 Scattec Plot of Unconjugated 8ilicubin and PFS, Decatur, 1997 Unconugaiodbin 8y FOS = 2 i io 3 0sfo --] 20 am pros ee am rom r--PaoyrnoFrmdiegraee=l2 UncobunnUnkea0r.gF4e726a80.t004e8 PRdOS Rsqua are SummofFau o"oSrosrsose RfSoet eth are Ero eum wg Sdiistrncwet= Srfowoke OF: sAumoonroSowafuaVmsasnsce MeMmoswswee Summ cones SCFeireea ow 8 33mm (1 TFoomew Cr [ onus i -- SuEmre take prob oud Soe 53 Sam Unconigated bin P0o5mo0P5er8e4kgirenePeR2OS + 0.01076 PSHE Samayott Asquare 0077372 001225 RAoSoqtuMaereanAdSjquare Error M`OebasenrvoaftRioensspo(onrsSeum Wats) 00..015946509815 0.46309a5 MSooduerlce ECmTootal Analysis of Variance OF2 Sumo0l2S6q1u1a7r5e0s Me0a.n1S3q0u5a88e 3F.R3a9t63i 881 33a171s4s4e2s0z2 0038450 P0r.o0b3>83F ITntoormospt PRPFOOSS'? Parameter Estimates 05E5s4ti0m1at5e 0S.U0EMm%o4r7 00001807567058 000030348158 1t2Ra3t3o P<r0o0b01l 228857 0000112179 001226 APPENDIX C HDL and PFOS Scatter Plots DRAFT 001227 Scatter Plot of OL Cholesterol and PROS, Both Locations Combined, 1995 HOL CholesBtyePrRoOlS To sq" OL. 70 - Lt I=odWieELLi . 3 owdaefnAFTe,NdEA Ls - 2 1 o0 200 4 60 800 1000 1200 `1400 pros --UnearFt -- PolynFoitmdeigraeel=2 HDL Cha=ln5e1ea.r01Fs0i7--t1.1o750r8PFoOS RfSsqquuairreeAdi `SummaofrFyt oc0ao0s2a7r MFoeoatnitsaRneSsqpuoanrseeEro p12r5e01d1 Observations (orSumWats) 174 ESNomoudrracre OF5 ASunmaaolflooSzfayVeeasssraincseMemwSoqtusw:e sFariaiso 12 riser 157685 prowr Cow 7s reas 21a oes PTrnotoomrseapt sEisPaotraanmseterEs1Stium4Eatm7ers Assoro Poroabatr) iS OSoessy ase oss HOLCholesterol = 5P3o.y5- 23o.F3i80tm5d36o7garPeFelO-S2 + 0.25758 PFOS"2 RSAqsuqaurreeAdi SummaorfFyit oiosiazses 001228 MRoeoatnMoefaRnesSpqounasree Error Observations (or Sum Wats) ana12s.e4r4r3 176 MSooduerlce ECrTootral Analysis of Variance OF2 Sumol14S89q.8u0 aes Mea7niSdqgu0a2e R48a10i8 7jal 2276946755261184 154828 P0r.o0b0o83F iTnoemrospt PPROOSS? Parameter Estimates E5s3t5im2a0t5e 1S8W9E8m8o56r 9032057557738 101.6102663577 2t8R.a1l9o Pr<o0b00l1] 228054 0000403540 001229 Scattec Plot of HDL and 90S. Antwerp, 1995 HOLGholasol 8 PROS oJ wl. 70 . . 3 odOkai , . IS RY oa wf ent. gwd Lo 2 10 0 200 400 60 800 1000 1200 1600 eros -- tnowrFt ~P~ olynoFimtdiegraeel=2 HDL.Cholostaro 5n5e.a2r9F81t ~ 0.63385 PFOS AASSqquuaarreeAd `SummoafrFyi 0000018057337 FOolMeeoaatnnMaataRonensSspa(ounxasSeeuEmrWret) 2320s8as8 SEMoordureela OaFi SAunnoralad2Slso6wfa8yiVm0sasrse2iiansce MenpSSqoiuwres Frac Pme Taw & Taisen oor TPoarmoasp scSPaiarmmamseeterEsrStueaEetresoser 2(0Ra1i8o Psrooobtl Sis oes Am aie HOLCholesterol = P56.o91y- r26o8Fi6n5d8eigPraReeOlsS +024725 PFOS+2 Asqure SummaofrFyi ooss0se 001230 ARoSoqtuaMreeanAdSjquare Error MObesaenrvoaftiRoensspo(onrsSeum Was) 91021300386072 535[3 SMooudrecle ErTootral iTnoomrospt PPRFOOSS'? Analysis of Variance OF2 Sumo4f4Sq0u2a1e2s Mean2S2q0u1a0r8e 1F.R45a2t8 8a75 1132837178.070808 151503 P0i2o0b0s7F Parameter Estimates 56E9s1t0i0ma3t4e 2S4U08E2m7r6 02267s2e4s6s6e 012726858028 2t3Ra6i2o P<ro0b0a0f1l 115028 00.21832234 001231 Scatter Plot of HDL and PROS, Decatuc 1995 wE o e HL Croesus By PFOS "0 7 wl. * 0daCfahey ee g 30 : S.C eT . - 10 o 200 4 600 800 1000 Pros -- 1200 1600 er --PoynoFtmdiegraeel-2 HOL.Chol=[4e5r.s3r1t7- 0e70r67oPRlOS `SummoafrFyr FoRRsooqkmuauMrraaenASdureErr ooTooot0sisss2earrse CHaismanaorfRoessporsssumWeis) wmw EVSroutrerre Sow T[ ommeeps OF7 ASumooiaSowfyaVmassrnses MemSwe fr Shee rFRoswio oo 10o1i722134000 Harts soasmt asGPTamreassmeterEsvStaeutesgs i5na%io PLroobnar Soiess cee as aes HOL-=4C7P.1o8h0Sl2uy2mo1nFm8io9taodlm0fre8giFyPrieaeReO=l2Ss+0.1t542r2 PFOlSF2 Asquare 0.026208 001232 AFosoqtuaMreeanAdjSquare Error M`OebasenrvoaftRieonsspo(onrsSeum Wats) 0100.084877022 433023a3 SMooudrecle CETrootal Analysis of Variance OF2 SumofS2q8u6a3r7e6s Mean1S4q3u1a8r8s F1.R20a81t 8a3s 190813274716440 118527 P0r.o3b04o0F InTtoermcept PPFROOSS' Parameter Estimates 47E1s8t0i2ma0t1e 2S7W8E2m0o8r 02115820202822 0151243765084 (1R6a8o2 Pr<o0b0s0t1] 114047 002.819485 001233 Scatter Plot of HOL and PROS, Both Locations Canbined, 1997 Hou Crasseiy PROS = w nd"... . 3 PoE fCalAl NELn "PLPPaEsELxEhRate ve ] o 6 100 200 300 430 6 630 700 830 odo 10m | 1260 ros i --PoFot dor roe2 HLCM [465--278 0.45120PFOS Rfoqmue) Summary1 aSchnaee RRooaneoe dsr Er oosse `Observations (or SumWgts) 149 fSoue OF? SI umorr sTcgtuoVsawea tace MemnMSUuwIe bFaote E5 R A a Ta om a CPoiannsa EhSsmereme tRweo PSoeondn le EE mE um oom HOL holesac = 4P5.3o473r1o0F0ni2c0ie3raeFnOlcS2 0.08804 FOS+2 Asus SummarFyt aconrrs Saraadi Sooores 001234 MRoeoatnMoefaRneSsqpuoanrseeError `Observations (or Sum Wats) 4150.650329112 149 Analysis of Variance SMooudrecle OF2 SumofS1q0u1a.r5e3s6 MeanS5q0u9a6r8e 0.R45a3o4 CEmoo l 141488 1186451113101417 112405 P0r.o6b36o3F InTtoemrcept PPFROOSS' Parameter Estimates 46E8st4i7ma3t2e 1S6W9E6m3o67r R27a6o2 <P0ro0b0o1f 01d0s0s2s0o6s2 O10314837T0E8E52 007477 00.46433780 001235 Scattec Plot of DL and PROS, Ancueco, 1997 aLCron 0s w w no ow f LR IY 0 o 13 200 33 30 3r5o3s0 790 00 300 ako | 20 pr ~P~ olynoFimtdi egraeel=2 HDLCeSon30l ne28aw84r0s .4113o 1FS ToBassraurinsita: wiasiomseuss em 4 SB e suwm o gO8F sAmnuELsaPoalomEafyeVmmassdaincseMenwseouRmms stoFoaemeo wBToeme uwCaomhrae EtSSmeeamEmna hWWaEehoPomt HDLCroat 5o4Sr5u0mtm1an87ra0FycPFeS +03084PEOS'2 Rsumas oRsiucen 001236g MRoeoatnMoefaRnesSpqounasree Error Observations (or Sum Wats) 419068746953s24s MSooduercle ECroTrot Analysis of Variance OF2 Sumof1S6q.u3a0w2e6s Mean7S8q1u5a1e 0F6R6at3i9o o6t2 772404728115248 17708 Posrtoebs InTtoermcept PFPORSO'S2 Parameter Estimates 52E4s2t5i0ma5t7e 2S8W8E8m0o00r 043106075841127 3086316495587 1tR8a2i0o Pr<0o0b0l1 11.0105 0022851349 001237 Scatter Plot of HOL and PEOS, Decatuc, 1995 HOL Cholesterol By PFOS. 0) 5 n . 01... - OF FSNeey Le o PE ErF te " FUN 2 10 o 0 1.00 200 300 400 500 600 800 9001000 1200 Pros -- UnoarFt ~~ PolynFoitmdegireae=l2 UnearFt HDLChales=t4o23o28l1 + 0.00268 PROS SummaofrFyit RRssgquuarreeAdj S27o1r2z0i7 FoMooatnoMfadRneSsqpuoanrsee Err 9229337m59 Observations (orSumWits) 8 AnalofyVasraincse SNooudracle OF| SumciSBqooures MemnOSq0ui1e 0.F0R0a0t0o ErCoorwl Po 770082368864677 sari Pr8ob%or ParameterEstimates TPInrotomoscapt 4O2Eos3ctc0iom6sast5se 1oS5SW0s8Ew1ms3rs1 2t09A00s07o <oPowro0eb0rN PolynFoitdmogireae=l2 HOLCholestero=l 42.5-03.2400821 PFOS + 0.02723 PFOS2 Asquare `Summaryof Fit 0.000231 001238 RAoSoqtuaMreeanAd)Square Error `MOebasnerovfatRieonsspo(onrsSeum Wgts) 304032844755. 423389 MSooudrecle ErTrootral OF Analysis of Variance SumofSeuaes MeanSquars F Ratio 812 70811.06333343 87o.s4i2e0s2 P0r0o0v93o 8 70826667 0.8507 ITnocmapt PPFROOS.S2 Parameter Estimates 42E5s3i4m8a4t7e 21S4W3E1m8o0r 00220r0z22T13 011580811832 (1R9.a8o5 P<r00o0b1 00.1143 0098090172 001239 JOEM + Volume 41, Number 9, September 1999 799 Serum Perfluorooctane Sulfonate and Hepatic and Lipid Clinical Chemistry Tests in Fluorochemical Production Employees Geary W. Olsen, DVM, PhD dJeefsfnrietyh,H.BuMrasnd,elA,N.MID,aHMPH Larry R. Zobel, MD, MPH The 3M Company manufactures fluorochemicals, which have as @ precursor perfluorooctane sulfonyl fluoride (CoF,SO,F). These compounds maybe expected to transform metabolically, to an undetermined degree, to perflucroactane sulfonate (PFOS, CoF;,S0;") as an endstage metabolite. Subchronic studies in rats andprimatesindicate a potential for cumulative toxicity with PFOS with the primary effect related to metabolic wasting with hypolipidemia as a consistentfinding. Biennial medical surveillance has been offered to the company's fluorochemical production workers located in Decatur, Alabama, and `Antwerp, Belgium. In 1995, the mean serum PFOS level, as measured by high-performance liquid chromatography mass spectrometry, for 178 `male employees was 2.19 parts per million (ppm; range, 0.00 fo 12.83 ppm), and in 1997, for 149 male employees, it was 1.75 ppm (0.10 to 9.93 ppm). Our analyses suggest that among these production employees, there were no substantial changes in serum hepatic enzymes, cholesterol,or lipoproteins associated with PFOSlevels less than 6 ppm. It was not possible to derive inferences from thefew employees who had serum PFOS levels = 6ppm. These results maybe due to the lower levels of serum PFOS measured among these production employees, compared 10 those suspected to cause effects in laboratory animals. oe Ml Depren, CoGmpnS5. F!ol ts Co Come5 Anon Cote ofOcipions sd Ene edn he 3M Company manufactures prod- desul nimeputriotriels.sotmhtonheave 535 8 precursor molecule _perfluorooctane spullafcoenyelxpfolsuuorriedem(aCygFo,c,cSuOr,Fb)y. iWnohralka-- tion, ingestion, and dermal routes. These fluorochemicals may transform metabolically. toan undetermined de- gree, to_perfluorooctane sulfonate (PFOS; CFpSO5") as an end-stage. metabolite. Potassium _perfluo- rooctane sulfonate (CyF,;SO5"K") is itassuerfalctafnt used as awetting and foaming agent in industrial and com- BU To, POIs Ban so spnnsea rseprt Te y In the plasma of rate? Tres pears be seman on CF es"oPFOS with 0 ania ind fous excretion 3 yin decreased the reten- [7 "0 yioibeled PROS in the 00 4 ach hd increased its Sudies in rats and primata es sugges there is cumalative toxicity wih clPoFenOstSirs.at*enltevLefoliswndeairnpegp,derswietrthoumbceutmoatuanllactcaihrvole-y tionxgicaintyd rleismulaitndglyin dmeeattahb.olAilcthvoausgth tthoerymaecihlansis5m ooftoFxliycunidnerlsatbooorda, lit imauymbpeodnuesntndo maenlaeboaflfimo,nmfeamy. TS rr pd 001240 800 veiVlollaunnctearoyf fbliueonrnoicahlemmiecdalicaplroduscu-r. pieornfoermmpeldoyseienscehathselbaeen r1o9u7t0isnelayt w3eWrP'ps. BDeeclagtiuurm.. Allocaabtaiomnas.. aTnotdalAnse.. raluymzeodrganniicl fltuhoerinmeidle-v1e9l9s0wserwehaennserum PFOS determination, quantifi- able by high-performance liquid bcehcraommeatoagvraialpahbylem.asTshespepcutrrpoomseetryo.f hseicstiosntauldyanawlayssis(ofptrhoevimdeediacaclrossusr.pvleoiyleaensc'esdeartuaminPFreOlSatiloenvetlos.the em. MeFituhoorodcshemici al Productiyon in FDleucoartoucrheimnic1a9l61praondducAtinownebrepgainn 1976. In general, perfluorinated owcrhogecamhnieicmcailcssaulbasrteprrapotrceeosdsius:ceeldaecvsuioaolluaytnizoeendleoci-nf anhydrous hydrogen fluoride at a low voltage." The products of this efellneudco-trprironolaydtsueicdst ccelolmproeaucntdison, defined by t awreithhightlhye he starting pmaotseurriealt.o Ptohtoesnetiafllfuoorrowcohrekmpiclaalcse tehxa-t metabotloPiFzOSe can occur in the emilxeicntgr.ochdermuimcmalingc,ell.andthepacrkeaacgtionrg, areas, as well as in the plant's quality `amsesnutralnacboeraatnodrirese.search and develop Subj.ect Selection surVvoeliulnltaancrey felxuaomrioncahetmiiocnasl mareedicoafl- f2e0r0edAnbtiweenrnipalalnyd t3o00apDperocxaimratperloy. odfuct1i7o8n emmaplleoyeemesp.loyIenes199(5A.ntawetropta:l npat=ed 8i8n:thDeecmaewdri:calnsu=rve9i0l)lapnacretecxi.pamlionyaeteison(sA.ntwInerp1:997n. =14695:maDelceateurm: nfe=w 8f4e)mpaalretiecmippaltoeyde.e(sTh(e0reiwncelruede10i0n etehse dpaatratiacniaplyastiesd. inSibxattyh-oyneearesm.plTohyi-s PFOS, Hepatic Enzymes, and Cholesterol + Olsen et al reofduecmtpiloonyeweass datuebo0th pllaarngte lmocoavtieonrs ldaunrciengco1ns9i9steadndof19947.meTdhicealsurqvueeisl.: wtieoingnhati.re:andmbelaosoudrpermeessnutreo:fsthaenidgahrtd. ctelsitnsi:calancdhedmeitsetrrmyinaatnidonheomfatsoelrougmy PROS levels. PFIOnS19A9n5a.lytshies analysis for serum ProFnOmSentwaals cLoanbdourcatteodrybyin3MS't.s EPnauvli. tMiynlnaemsomtoar.iuTmhe(0moent-hpoadiursewidthtePtFabOuS. einxtsraecrtuemd.'w"itThheethiyoln-apcaeitraste.weTrheethaebn- Iusmtstrianocgtaihopinhghpyr-ophdeurceftorrwmaapsncethleinsquasindalpcyhezrceo.d- wtreormeetaryn.alIynze1d99b7y, lthiequsiedrcuhmrosmaamtpolge.s raphy/mass spectrometry, using se. tlievcet-eidoniomn omdoneit'.o*ring in the negaLaboratory Analyses For both time periods and plant locations, United Laboratory Services h(Setm.aPtaoullo,gMicNa)l paned rsefrutomhercshtmeamniedsaidrrdy taelsksa.linTehepsheospihnactlausdeed (ItUh/eL)f,olglaowmimnag.: glutamy] transferase (IU/L), aspartate anmoitnaontsrfaenrsafseera(sIeUI(LI)U,/Lt)o,alalaannidnediarmeic-t bilirubin (mg/dL), cholesterol (mg/ dL), low-density protein (mg/dL), high-density cholesterol (HDL: mg/ dCLr)eamnrd trieglycmeridees (mmg/dLa).dClsineicmal oPnFOovSemdeitgehrtmifnaasttieodnbslowoedresapmeprlfeso.rmed DaDeascArnipatliyvse,issimple, and suatfied dainnaalryysesm,ualntailvyarsieasbolef vraergiraenscsei,onandweorre. PusFeOdStoaenvdaleuaacthashseomciaattoiloongsicbaeltwaenedn clinical chemistry est. Age. body mass ciondnesxum(pBtMioIn: (krginmk)s.percudrarye)n.t aanldccoihogl awetree wpoeten(tciiaglarectoensfsomunodkiendgpefracdtaoyr)s Fthoart wsetrraeticfioendsidaenraeldyseins,theemapnlaolyyseeess. were divided into four PFOS categor<i6es (p0p1m0. <a1ndp6pm. p|p1m0)<t3o pdeptme.mm3in(e0 whetheran effect could be detected at tchaeteghoirgihceaslt lseevreulsm wPeFrOeSusleevdelts.hatOtphreo-r vided similar results,Formulivarisble regression analyses, serum PFOS and atlhceophootlentuisael. caonnfdoucnidgearrsetoef awgee. BwMeIr.e ceaxlamexipnleadnaatsorcyonvtairniuaobuissainnd tchaeegmoordi-cls. Multivariable regression models were fitted, with PFOS analyzed a5 a cwoelnltiansuonuosnlvianrieaabrlet,raunssifnogrmaltiinoeanrs aisn fo0irdnddeirng.todaesmpsaeoxncidimaeitniztoenvstihbeletpeowsesoeifbnimliPetFyOtoSf pNeantduernatl. lovgartiraabnlsefsormwaetrieonspoefrtfhoremedde,when necessary, to. normalize vari awbteilroenesaalalnssdoteutptoiwlieisnzehedasn(ecsleeelcemtcoitoidnoenlpirfniota.cneTddruaordueistofmodel was set atP = 0.1),aswell astaking into accothoercuovanriattes that maybeonthebiologic pathway of ienffemceta.s'uWreeddiPdFnOoSt beextawmeienne cthheantgweos thiamlefifpeeroifodPsFObeScaiunsethethseereusmtiimsatbeed- lieved to range between 1000 and 1l5i0sh0eddadyatsa(Jb.asH.edMoannd4ely,eaMrsD.ofusnepruubm- measurementsofthree retirees, 1998). Study results were analyzed using the SAS System." Results serTuhme dPisOtrSibuteixonpoosfureemplcoatyeegeosr.izbey: tWihoenr.eaiss 2p0re%seonftetdhe inDecTaatburleem1-. bpoltohyeeyseahras.d ethxipsopsruorpoaerstti=on3 pinpmAfnotrwep declined from 25% in 1995 to 135 in 1997. For both years. 95% of wtheereembpellooywee6s'ppsme.rumThePrFeOSwerleevenlos APFnOtSw.erpmeians1u9r9e7m.ents =6. ppm in 001241 001242 em-- JOEeM r-- Volume-- 41, Nu-- mber 9,-- Septem-- ber 19-- 99 --e te--e--e --tt --e ----r e801 DTisatrtieb1ution of miion ip) Employees, by Year, Location, and Partucrooctans Slfonate (FOS) Exposure Level (in parts per 1005 00a Atmpioyees nwo Oscar 1997 oma MGmposees Anwers acsir dlemidomsnn wos w2 8m wnw w m %as wns u w aw w& osaawseamaoa w% aowmsemm swohw=T6Twm oaons uown 85 onw oron TLTo. m Om w.m .wSw.O..wJOwU.J.esONw . s.20w.o WET PMaeraanmeVtaelrusefsoorfAPnFtOSw,eDarenmpdogDreacpahtiucrP,, S1e9r9n5umanCdhem1i9s9t7ryE,xaamnidnaHteoimoanntsoolaotgisc uate An vtwer, t Deca AnT twerO p DeM ca sPgGnS.pom ont E Ts L24 ey: Bt E 148 A1% of 28 pA ratapionobad w eown he aa A ast I z= J Ge a`ss oz: ow =oss inion, mje 02 on ae om Sa Cholesterol, mg/dL. wn 2HW 14e E528 2= m 08 Waas r "ihymas rAs r maahartsps:r GaT oar gay {o LOL. a AST, para arintanslaras: ALT,anteman low-density poprotein: HOL, high-density poprotein. tr a s T+ i 3 dvs sra`pThhiecm,eaanndvlailvueersafnodr PlFpOiS,tdesetmroe-. sults. by location, are presented in pTlaobyleee 2p. opTulhaetioAnntwwaesrpsigmnailfeicaentml-y younger than that at Decatur, had lower BMIs, and had higher self- HroelporItneaddddiatiiloyn,cothnesiurmcplitniiocanl opfroaflicloe-s bwoetrhe tdiimfeferpeenrtiodfso,r stehveerAanltwteestrsp. eFmo.r applhnoodysephehisagthaehrsaedtoatnalldowberirililrymucbeeiarnnidaenadlvkaHallDuienLse vaTlasb.le 3 lists the mean. median. sandurd deviation. and range of the lceosvtaerriola,tensdanld iheppaotipcreonbztyyemoeisun,rclheov-. els of PFOS categorization Oto <1. t1h1e0c<o3m,bi3tneod <p6o,puatndio=n6s pfporm)eafcohr surveillance year. (Hematology and other clinical chemistry data were Suenvreermaalrkobasbelrevaatnidonsaraerennootteswohrotwhyn.) PFiFrsOt,S tchaetemgoerayn wfaosr tohnee =or6derppomf bPmoaFtgOhnSiyteucaadrtese.ghoAirlgyshoe.(r0th1te0han<me1athnpespmol)ofwetfshoter cfaonutrlyPdFiOffSerecnattefgroormiecsacwherotehesri.gnSiefci.. ond. there was only one variable. (cul bilinbin. that had significa Sm{tePaai<nfsi0ca5itn)iobnkotbvhyeisypelfaaenrrts dlooficataninoanltysainsId.n Gvgniifliclan:efinydeianrgsdfiodr onroatl rbeslulitiinn e or direct bl ilirubin (Ti able 4). Third, (m1a9i9n7e)d wciotnhstahnitgh(e1r99P9F)OoSr icnactreegaosreyd levels, although the HDL mean val- glueoosryaetaersienowdniesdthltSohuweaeirHfiiagchmaeostntognPRtbhOyoSsepelenamen.-t location and suneillance year did PnoFtOSreescualtteagionriseeisgn(iTfaiicbalnetl5y. dFiifnfaelrleyn,t NitehoWulIdNEbSe nPoiOdSthctteemgplroyyeerse1 O`1edmeprloaynedeshidn thhieghleorweBstMIPsFOtShancadtiedpgolroyy.eeFsurwtihtehrm=or6e,ppinm 1s9e97r,umthPe FeOmS bclleoevneflosDuiwnedtrehedusobntelhcyeaufasrneoamlyDDseeecscaatumurary(eTmba.eheplaovyieeers twhearne Agnetnewrearlply eomlpdleoryeeasn.d For example. in 1997 the mean HDL level for the =6 ppm group was 40. mmega/ndLval(uTeabwlaes s3)o.lelyHofwreovmerD.ecatthuirs empLloyieesa.nndnoenlinaear relationships cvboaerutinwatebeltenhse oPpfFoOtieSnnttrieaaslntd,cottnahfkeoinudgnedpiietnnogdeaancf.tafercettseosf rageev.ulBeMdI.inalmcaonhyo.l.aannadlycsiegs. Tol bilirubin showed 5 signiheant 001243 802 PFOS, Hepatic Enzymes, and Cholesterol + Olsen et al TABLE 3 ManedanD,ecMaetduiranE,mpSltoanydeaersdCDoemvbiiatnieodn,(fSoDr) 1o9f9M5e{ann=an1d78)Raanngde1o9f9P7F(OnS=, by Demographic 147) and Serum Chemmistries forAntwerp. 1995Data 1097 Data PROS" (opm) TRG,pom ~Mean Medan 50 ~ Range Moon Medan SO -- Range -- 0Tto0<<13 31< 014892" 015707 002%7 1000208010 017S8 01562 002%7 011002110002987 412) 397 081 300058 IE 35% 070 30010530 = FBaITl=3v219e.P773< 0002051% 606to128 Fv7a2l0us = 367.66,88P <0.0010513 6051093 AgeO,tyoo<ur1s 10<3 aar 3 89 2s1o05s8 3a @a ons 22101100862 3=t0<6 3 a 77 6S0T5s5 a 2by 55 221005524 `cohol, drinksperday Falue = 37.7 = 002 Fa = 5.1v .7=e 0.002 O1t0o<31 0o8s oors oosr 0033ss 00ss 0o11 ooss 001w045s0 32t60<6 0172 003 1113 Fualue = 40, =0.09 o01w02690 0120 o0r1 0128 00100781 Fu=a18l,Pu=0.e15 B0Miok<g1/m 10<3 228157 26438 4528 1179960136877 22870 22449 4537 i18w11e04r85 32t0<6 272.479 22004 4328 2170S6ww30S 20783 227097 4440 198111t0033620 Cigartts,no.porday. Falue = 37.7 = 002 Fu=a21i.7v=0e10 B1l0o<<8t 3t0<6 2668 0000 1634 0o0o4wa0m0o 4872 0000 me3s ototdoo 108 80 124 000400 41 00 83 01030 26 Alkaline phosphatase, UL Fv0al4ve = 48,P00= 0003 11 00030 F60 a=l 1.50,vP0=0e28134 01030 o1t0o<<81 08 8nz2 sSwoises 877 s now 9ito10116332 3=106 88s B8s 22 Fave = 13,F = 028 2&t1o21ss 876 8nz1 F=a 12.Pe =032 62581100112104 Gar0t,oU<Li To<3 oa a3 121502s0 2386 F2I = 1100100114729 S=to<6 0a 31s1s Fuaive = 05.P =071 2B0o8m0 28 Z EA u 111007418 F=a 1.1.Pe =034 ASGTiUo<L1 To<3 22 sm12 110%% 2218 225 77 113511005563 326t0<6 fi 23 23 56 BB0y4 225 x2 37 21641004034 ATL Fae = 18,F = 014 Fa=05v ,P=e 067 oTt0o<<i3 3to<s 2" 82 2 a7 oBomies 33 E 3 n1s R100106808 Wloss 3 ER 1082 = . bitin, mg/aL F5a1 ve = 10,P =038 ar Boe F a a=09l s,P=e 0460 251048 oTtoo<<31 3108 [063% 007800 005X0 004200112S9 00677 00680 002410 003300100123300 08# 080 028 001d 06 050 031 0401130 = Fv0al7v6e = 4.4.7O7=00005 02 006120 Fv0%a= 2l9,0u 75-0 0e0402 04010100 001244 ra-- JOieEeM-- Vol-- ume 41-- , Num-- ber 9-- , Sept-- ember--1999--------------------803 Continued 1005 outa 1007 outa rseiPnOSmGoao. es Mam Medan So Fangs Mean Mede$s5 ange a052 oOXm o00ms ootmbwwoawk ooii o0l0 b0h0 oowwnesm . 3&05 i Chola,mya. FraGai30n =08.50O+%k058 0o0m oomwwwaasm} Foolri =3a5.i5oo+iln002 a5m% oowlnoweeds \:! 5f=Otoo%s<1 ZBB21ese9 da m 2M5 X 3&a7 1sme00eteomw3ms40 mmm19eee8 m sm19es7 B4B60m ihl11ee0m1en02ess80 LohLienega Fake = 055 - 038 Fi=43n5 -e 0008 B wo oweGo mdeewm owmm m ws now gseemm 8& % FWWieakeo=0o2.W5 -oB ar MabHiewes F dasw a=27n.d17em=eoorx meeeem HFoTuremejse. ws s @2 km onNoWw sRheeemswo 6o0s 5 w o0n0B Zwpeoeann 8 rr Frae in =h 29.5 -h 00 Gen FBoo=o10v.s7 =o03 T 3ew TSeeesrs & W wmdR emwm lB hadeeoeeens ddw ee w11sm odasw dew ame de & msmeeeaukms eel Frain = 1.7 = 035 Fa=0n 87 e067 TM3 aeSannTsssSrcoiacnannttyyeaaiffar(2<< 00..005,BBoorriaerroorntDDuuret6e6st)Foorntthh moanooff 3he<t1hrPPRsOFSEcOaSgeasg.. * aan SgacantySwan 2 < 0.05. Briar ir 168 Fon hmeof <3pe PEGS coon. Deqcuaadtruatriecmapslsooyceiaetsi.oTnhwaittsh,PtFoOlS bfiolr: irubin levels inially declined but srahbolweedannaol.ysceosnsi(sdtaetnat naostsocsihatoiwonn)s between PFOS and HDL. For both wweerrep baned l6Depocpamwu.r Beemcpalouyseeest.hewAenrtedissimilar by age, Bs. and elf. suinbgseqPuFeOnStlyleivnelcsr.easTehdiwsitashsioncciraetaiso-n was not observed in the Anwerp spilgannisficcaonmtblyinende,gatHivDeLly leavseslosciwaetreed (nearly) with PFOS in 1995, afler rceporoted maalocowhbeollulsaie,swenpearcaeotneadundcltyedsce by plant location. These three Heimgphleoryfeoeal pboipliurluabtiinone.velw.hiIcnh19h9a7d, serum cholesterol levels were posic afactodrs.jbutfuotrhpisoswsatisbnlmoetcooenbfsoeunrnvdeidtngin 1997. pdareiahm: wohyfgactthroersAaenxtpwpleariphn,eamitpllecoasyt ces had lower mean serum trighycer- tityassociated (nea)wihse. po des andhigherHDL levels thanthe ' DretucenamtitPaulFrOcSeo,nfamofutenprdilan(dgdjaoutfsaatcymtneoorntestsfhoaeormwopnsno)g-. DainasWlcyeussecssiooofnsnurdtvwuoecriocsdlsa-lttsaeacettnoiocdneaexl- nDeoCctalatnuisralesmhpelpooayweicetshe.int"zhy2ema?eemtpelsoesyeweedrse: This association wasnotobserved amine the associbaettwieeonnses. serum PROS. levels. This wet an iw1ni9t9ch5itshaeemrroutmnigmPeFDOpeeScraiauondrdwecihmtohpleltshtoeeyroeAlnoetisr.n iornluomgmiaPclFaelOaSfnldulecovlreiolncsihceaamnlidccahsleevepmrraioldsuhtctetemrisaoyn-s cabiemupsoe&r_tPapnRetOroSqxhuiaesssotmbieoe.nnptrroepoofaredtrdesrdteosrs(.1)b1ie0n- wdeartap beympplloaynete(sT.abSlterat5i)fiacnadtimonuolfitvhae- tehmeplomyeeaessu.redF.orsbeortuhm yePaRrOsS,.95le%veolsf prlaaissm'a'; i(v2e)r ltoanrseasmuiltnasine einscsreaisned8 001245 804 PFOS, Hepatic Enzymes, and Cholesterol Olsen et al TMAeBaLnE, 4Median (Med), Standard Deviation (SO) of Mean and Range of PFOS, and Total and Direct Biirubin Levels. by Year and Plant Location Antwers Decatur wPorwos pom) Mon Med $0 Regs Mem Med SO Fangs -- -- T direur, mal Toss 00%8 00880 00525 0040020%1 0085 008%0 0om6 004201005008 s26ss 007%5 Fualve 007%0 =12.7 = 031 00235 0O706Nw1i2d F 00561 u=07s 00.78s=e 054o01t0 0200s106w100n0 0. Gbiottin, mora Tos 00228 0022 00006 0200X004%0 00220 0022 0o0m8 0012010000420 3=e s 002210 002200 000m3 Fualue = 07,7 = 055 00220000230 F 0022 =a 0.400.272e =074o0m0 001200110033 19T67iDruutbai, moje Toesr sss 006% 075 00780 002d3 070 040 004X0012 01 006%3 051 005800 050 001380 O16 003%1wi0d 03015090 BS Fa=ve =23rPo =011 Zz F0% a=10l0.570=e04102 oadio1e0 . Gbwin<bitn, gia 10 0011 O0f2 000058 001100000420 0O031 00100 00008 001100110000320 i305s 0i1 0-10 0=0s Fave = 22.p = 012 00K=02 F O0011 =a 130.01170e 0=028000@0 00110016100120 Testa Tebm ye e -- -- sinucbrceharsoenisceruramtassptaurdtya't;e aamnidnot(3r)anst-o Cinom1p9a9r7a.blWeepearrceenutnacgeerstaailnsowehxeitshieedr tfaesreaselevaenlds lionwear saulbkcahlirnoenipchorshpehsau-s pmoolsytsciosl,ielicgthot,n afancdtohresa,t,incclouudlidnghahvee- moTnhkeerye satpudpye.ars to be significant bicloirnutbirnilbevtueotltsebhdeetdwiefefnertehnecesAnitnwteotrapl wemittehrobhoetphuatriicnarciyracnudlatfieocnal oefxcrPeFtiOoSn and Decatur nately. toal beimlpilruobyienesw.a's nUontfoarntau. qiunatdhreatriact*r*elaAtlitohnobuegthweweenoPbFseOrSveadnda kIeyzyedstiunditesw,o wshubicchhrorneisculttehdesiunsdmeoant.h afonuallysbeislwiibtihnthien Doeucratmuurlievmaprliosybelee ~~oPfFaOlS adnoismealgsroiunpthoer 4h.i5ghmerg.l"gidOsny- dpaotpaulaitsiodni,ffiicnutle,rpgrievtaetniotnheofnatrhreoswe going toxicology primates should studies provide ianddraittsioannadl artaendgewiotfhPtFhOeStostaelrubmililreuvbeilns vaaslsuoecsi.- capleresfpfeeccitvebsetrweegeanrdPinFgOSanayndbiboilloigriu-- cInetse"rteosttailngbliyl.irutbhien lAenvtelwserwpereemspilgnoiyf.- binOulervedlast.a do not suggesta reduction pilcoanyteleys'higlehveerls.thaWn ethesuDsepceactturtheemr-e aitn tthotealsesreurmumlecvheollsesmteeraoslurweidth PFOS among bemraty'sbesyangdreraotemrep"reavmaloenngcethoefAGnitl-- tpheersoexpirsoodmuectpiroonliefemrpallooryeienst.hPeFaOtS. ainsda werp employees. In 1995. 15 (17%) Antwerp employees had total biliru- hypolipidemia has been consistently observed in subchronic atand primate wbiinth vtahlrueees (231%.)2Demcga/tduLr.emcpolmopyaereesd. toxicology studies." Rhesus monkeys tha had been administered PFOS acthol4e.s5termoglkvgaildueasythhataddecmreeaasnedsefrruomm d1a8y3s.'mgR/dhLe.susto m9o9nkmegy/sdla.dmwiintihsitner3e0d l1e.v5elmstgh/aktg/ddecaryeahsaeddfmreoamn c1h9o5lemsgt/erdoLl tobose1r1v1abmleg-/edffLecwtitlheivne9l0wdaasys.seeAn nfoo-r Stheeru0.m5 PmFgO/kSgmdeoasseurgermoeunptastw9e0redaynso.t Hdoewteervmeirn,eddatian fthesrearorheecsmeunst mcoynnkoemyosl.gsuugsgemsotnekdetyhadtohsey-proalnigpei-dfeimnidainmgasytubdey ilniteialilvny taehssolrcainasgteedofwi1t0h 0s0e2ru0m0 pPpFmO.S" tHhaatugthheohmypoalnidpiSdpeymdiecveoflfdectsoufggPeFstOeSd hmyadyrboexdymueethtyolregdluutcaerdicliavecriadc-tCioviAtyroe-f daucycltiarsaensfeanrda.se.acwyilt-hCoAe.nhacnhcoeledstfeartotly acid oxidation inth liver" Nabbefeld eatffianlitoybsfeorrvtehde tfhaatttyPaFcOidSchararsiear hpirgohteins albumin and 1faty acid-binding 001246 PC JOEM + Volume 41, Number 9, rrr September 1999 TMPlheaaanLnte,'LsoMcaataionn (Me, Sands Devito (SD) of Moan and pros: pom) Aatwers HonWed so 199C5ha TDaoottsaas, mya. - mBwe wae o@w Ses vou mga Fl2Boe =08m Em8s 00W 1 ko Teedss e 8s 0 w&8 o8onn 58% 19C7ruan. me Fuako = 11.5%038 wNossn 8 2ZW 3o wm Bm wwan . w= = vorfuemesgsa Fue=20,5 =007 aswkB1 s= s Fu5 ae 0% 2 8,5 = 047 0oBr Teme ame Rango of PROS, mse wmmoeeewmsse ewe SSseeennx Gem tmmoeewnemsr mwoweeensn 808 and Total and HDL Cholestos, by Your and Ducate en wei 55Fame Ba2ms dw awhnee de 83% 6 msiwemamem ime Fo=0o58n089 8 oo8w %a4g09% Egseeews F2a=0u14%.v5 0e28 1 mew dfwemw smme enow ujmseeeemdm FWi=G 20n5-n13 RMR 8e 8&s48 505 mmBeeessm F" =u 05.%5e087 0 pes |" i protein in vivo. This could pondally Tiswasdue, inpar 0.large tm. assedwith cleIvvear tranesadraalntder fmaetbyoalciisdmt,ranswphoirtc,hbicoocnhceemiivsatbrlyy, towveeeronefxeammpilnaotyieoenss.atSibxot,hhpelraentcsobued- inIanselseuvemlmsa.r2y2,5ou findings suggest could thenlead 0 adecreas in cho lesterol esterification and. metabolic be measurement ero i imporant confounding variables. Analyosfithse (ht among these Anlwernond hess. tur male fluorochemical production wsahsotuSeilvndegbr.ea"lcmoetnhosdoilinogedivcaleaulartiinegsstudhese pdWaaaetsadeoxifcnebtlhleehnt6y1ceaosrulsbjtseochtonswefwodhoUhipearDtoirncie.- cechmhapatlneogsyeeesrelsin,, tShoerererpweonreeepantioeasuobsmetanentinsal dr siercete citonfas arlonu dmeosual iogrnfst dlttouhdces yyst.nesoFmtpiioanltrlshloeyswcroftoosfa,sanrassociation. Sectheovolnumardy p,ar. fo0Fu.o0ln0d0ic1n)og,nfssaeuclmtfop-rriesopoonfrtBe(dM+ Ias=p(erc=t5s89 ,of2PaPl,=c=o 00001). and claret smoking ( = paemtoiremned.nswciIeettshnisPfoFrnanOomteSshplosesvseoilbsnplelpcestosopeltdhoeamreniive6e imeidpiuciaoln surveesiliannciehe wMeorreocnhoetmiidceaall mo the ln igble fuorochemicalpro- 611 9e,mPpl=oy00e0e0s1c)ruAms PcRxOpSecltvelsheose t2hyeaers wre highlycomsied (1 oSneoamfion sstypetlems seni aes ong oe dleuvcetlisonofemPpFloOySest.htThwier.e tmheessaerreudm may be below the Noll evel in G52i.f7 f=o0m.00th0o1s)e Tofhtthereesnseiddnyor population. Finally. th. qulty of FPasasBran1n% AoeMs oEsth 5em om,ros TEISUSdamongthese cbonrstryparniimmaary iFnotuheriPveOSofcaobn.. ortory amas Serum messurements mueifolr ssuiunlglaen adapsi. ypoproe0sf.s can fen be evil by whether SP7o0o1Caes MPA Mil hoess obfodPyRObSurdmeany Fnoitl.adetqheuattewloy rcerfloescst sections] analysescannotbevieweads kvseanrroviewodun.s Iepnxopsheiicsvteerdegaaassrssdoo,ccwiiaaettiidooinnsd. aosrbuescehorvabe+ Acknowledgment eindmeppendlenwoteryeposeptuuledatiiesodnsi.n bSoithxtyye-aorsn.e cbilgoaordetccelscmounotsaknadniSdenalatgeged BwMhIe. sTshkersauboafrssi radtubleyenscksowce he 001247 808 References 1 G, on SI. oman 10. Ont RE Ah BOS wdTEoe Dstt, FO"C InFessy a at ony e E e Fe o Coon1F4"e hoaye rege No 900310o30r0,eoov. FPeuo,siMCN. 3 RJihvoenLaTov.rGaivsenIn$s1.1O9v7e9r RE. ChoClesbyoranmi1n4eemnhtaansceadesfoasdmchiismisnisoionn ooff Samm[m[CC] leppefelrurorfoicoarnemsalsfoormripeo.r 4.FuGnodlAdpeplnTEaLs.cJoesso1p98O6C4,9G7ei2l97R.G JefacfuetreonRNrD.TovAircckcyoSRuJd.s.NiSnteudryy:NDoa.y 1Su3b7. 035 Matava, MI. InematonalResearch 5. DGevoellodpmeennEteL.CoJres:soNpovDeCm.bGeeril19R7G.Je ferson ND. Nine. Subacute AES Moker Torictss Suay, Sudy No 137- 2s0easr.chhonDev,elopmoehnt nsCeoropaionstDUCEBee 6. Gwolsdenthal EL, Jessup DC, Geil RG, Jef- Monkes ToilsSude. SatnuedsiytNeo o1n3s7 E3 e wo: nt Spara(hrosc, eCoCoenomTeelcogku)s aen os30rar wa, 8 Kledos.T.mFSuogicaaTIKn.uMctoornIo,fByrcohmoemMe,. vPeSDbyapnedrpteooosniuseodmeccpaonreastliioonncnacird. BInioFlogay HaDnd,SMeesdiocidne.. PeNreniwsomYeosrikn Springer Veg: 1987:3404308 PFOS, Hepatic Enzymes, and Cholesterol + Olsen et al ( h vim un C nder8ly.inE S g th d0hOypToNlhpeTmpic hefect 10 GctironnninicpM,idemoio1lotgc -oa0snadly,ve iMurcctanesdsulphconhic ooidB(oPFhOsSAYAatnd 17. SSASu.cI.nsitVee.rsiIonnc. 5.SACSaryU,serNsC:GuiSdAe:S 10, S1o9l21e1m2n66A5K..72Erkan AVL Hogsom 18. Dnaviecn TJ.InS;c1h9a0rchid BF. Biochem tC.ocKainmelasnudlfoMn.ic Daudp1rseonJW.tPiendrulce.r McaHl,eSrchearsc.hmIindeFeBlFd,meadns.MG,Ssetrsaeinigees-r aonfdpoereorxioscmisvlitoesyknaociwdntboebweoxaiffdeictoend pinhaal,anPAd:LivWeBrD.isSaeunadeshresd,.CosPhil1a9d9e3l: BnyerpePrhoaxrimsaocmoel Tporsocfoes9o3r72in90m9o3u.se 19. L1e1w1i2s-1I1A22lasted Gude to Diagnar- 1. NA.abDbieseplladc)emBenuteolf ,4Jf,luBoarsesscNe.nStleycslt= iCcorT:et1.99S4p1i0n0h-o1u0s7,e,19PA4:-20S7p.inghouie cbalemdeapryoteicnisdbaysWloygeuteh 1f4r6o5m3a, yammsiod. 20, Fprainecdemsa.n InL:S,TiLeivmeery, LbiMl,iarMyccPhtee 1SnId. Riuuomrcopcetralnaeorsouolcfaomnoene3,ndpoovsesrukmnopwe.n aPnapdadTsrkeiasmeWnAt,. e3ds1. Mede.diScaanloDrido,goCsTi.s piecrlooxgiss,om1e9p8r.o4lf2e9r5a.tos (sbssc). Tox. 21. FApoplPeCt.onLiapnidds,Lalnigpeo:pr1o9t9e8in6,28a-d630p,oi 12.oBfrycfeoHr. oIndcuhsemissen.dwIn:ilSiiamnosnJps,ecods. pPA.oepdse.sLa.borIna.toHroyMweadniicainJeH:.TeHeoSweaen. dFeimaiocriereshsom1i9n6y4,297N49e2w. York. Acs. iChornchialnld LIinvteirnpgrseitoanteion.nc:Ne1w99Y1o1r7k5 13. on ID, Wale JT. Colac GE. Reh 198 will PA. Nelson RM. Quantification of 22. Wolf PL. Liver function. In: Howanitz. fPoernflsuriono.cHtaunnoaatneSanadrPuemrflUusoirnogolctoannePsiulr- cJiHn.e:HoTweasntitSzPeJ,eldsa.enLdacbIorntaetroiprrytoMteodnin- re denen a Sootw es Shmasil Liivavgiuinogntsone I1c: rSpeocromneirySt.WiPakl,AuMoN.rat3eMdESnavmiprl.e 23. ILni:doFleslkdymaS.nSMc.haSrismnigcekrBFM.iJ,uSdhiae.. 14. mAenndtearlsLoanborDaJt.orMy:lv1a9n9a. DE. Anayical LisvcehrmiDciBsFe,a6cissh.ee,dG.aPslroiiempeshtiiana:lWSon.d RreopcotannooarteheanDdetPeermoirnoaoticoinaonfePslefoan. 34, OSabuenrderGsWC.o,K1u9s9c8h22G0D-,22S4tafford BA. NteYinAHundandSeBrum sby LnOMS.Sheaicas, ~~ hGuedmluondwssenasSLc.atCounrrdeMsFg.: Tuhetpoys. 15. A1n0deAiuognusDtI. Molvana DE. Aralycal asurasnceumeditahao.ldfoOnrcoccucuppMaeetdo.ns1991.33 rRoeoptoarrootrtethaenDdePeefuromroiocnoifnaePsiefaoonon.- 25. 9B9u8r-s10C10,,BosIMw,OelselnGlV Liver aNtYe.inAHduvamnacnedSerBiuomanbaylytLiOcaMlSSelrvbisce,s cJOnzcycmuepacEtnivviitryonanMdedbody199mTa3s8s:1i2nd4e8x-. nc: Sepember 1997. 52 001248