Document LJ4ZReDXD8ZLqnaDmK03O3aZb

AU V IS _ IO'1 3M Company Page 1 of 121 FINAL REPORT Epidemiology, 22-3W-05 Medical Department 3M Company St. Paul. MN 55144 Date: October 11, 2001* Title: A Cross-sectional Analysis of Serum Perfluorooctanesulfonate (PFOS) and Perfluorooctanoate (PFOA) in Relation to Clinical Chemistry, Thyroid Hormone, Hematology and Urinalysis Results from Male and Female Employee Participants of the 2000 Antwerp and Decatur Fluorochemical Medical Surveillance Program Study Start Date: March 1, 2000 Protocol Number (not applicable) IRB Approval Exempt Expedited X ERB Approval Date: (not applicable as these data are from a medical surveillance program) Principal Investigator: Co-investigators: Study Director: Geary W. Olsen, D.V.M., Ph.D.1 Michele M. Burlew, M.S.1 Jean M. Burris, R.N., M.P.H.1 Jeffrey H. Mandel, M.D., M.P.H.1 Jeffrey H. Mandel, M.D., M.P.H.1 1. 3M Medical Department, 220-3W-05, St. Paul, MN 55144-1000 '(Corrections made from previous version) OCN=3> X =D Q zo "O rn er --m rTet rv> 12m oo 4rTo1 000133 3M Company Page 2 o f 121 ABSTRACT The 3M fluorochemical medical surveillance program is conducted on a routine periodic basis at the company's Antwerp (Belgium) and Decatur (Alabama) fluorochemical manufacturing plants. In the most recent occurrence in 2000, there were 255 Antwerp employees (206 male and 49 female) and 263 Decatur employees (215 male, 48 female) who participated in the program. This represents approximately 75 percent and 50 percent of the eligible employees at these two locations, respectively. Seventy three percent of the participating Antwerp male employees and 75 percent of the Decatur employees were engaged in production activities. Only 12 percent of the participating Antwerp female employees were engaged in production activities compared to 63 percent of the Decatur female employees. Employees' sera were quantitatively analyzed for PFOS (perfluorooctanesulfonate), PFOA (perfluorooctanoate), PFHS (perfluorohexanesulfonate), PFOSAA (N-ethyl perfluorooctanesulfonamidoacetate), M570 (N-methyl perfluorooctanesulfonamidoacetate), PFOSA (perfluorooctanesulfonateamide) and M556 (perfluorooctanesulfonamidoacetate) using high-pressure liquid chromatography/electrospray tandem mass spectrometry (HPLC/ESMSMS) and evaluated versus an extracted curve from a human serum matrix. A total organic fluorine index (TOF) was also determined by calculating the percent of each specific fluorochemical's molecular weight that was attributed to organic fluorine and multiplied by the ppm measured for each fluorochemical and then summed across all seven fluorochemicals. 000134 3M Company Page 3 of 121 Mean serum PFOS levels for Antwerp production and non-production male workers were 1.16 and 0.42 ppm, respectively. Among Decatur production and non production male workers, their mean serum PFOS levels were 1.63 and 0.73 ppm, respectively. Mean serum PFOA levels for Antwerp male production and non-production workers were 1.28 and 0.34 ppm, respectively. Among Decatur male production and non-production workers, their mean serum PFOA levels were 2.34 and 0.59 ppm, respectively. The mean PFOS and PFOA levels for the Antwerp female employees (primarily nonproduction) were 0.13 ppm and 0.07 ppm, respectively. The mean PFOS and PFOA levels for Decatur female production and nonproduction employees were 0.93 and 1.23 ppm, respectively. Separate reports have been written which analyzed the employees' serum levels in relation to their job and building location work assignments as obtained from a self-reported work history questionnaire. A standard set of hematological and clinical chemistry tests were analyzed. These included the following hematological tests: hematocrit (percent), hemoglobin (gm/dl), red blood cells (RBC, 1000/mmJ), white blood cells (WBC, 1000/ mm3) and platelet count (1000/ mm3); and the following clinical chemistry tests: alkaline phosphatase (IU/L), gamma glutamyl transferase (GGT, IU/L), aspartate aminotransferase (AST, IU/L), alanine aminotransferase (ALT, IU/L), total and direct bilirubin (mg/dl), blood urea nitrogen (BUN, mg/dl), serum creatinine (mg/dl), blood glucose (mg/dl), cholesterol (mg/dl). high density cholesterol (HDL, mg/dl) and triglycerides (mg/dl). Urinalyses were only assessed for Decatur employees via the standard urine microstick analysis, which tested for urine glucose, albumin and red blood cells. Six thyroid hormones were also assayed: thyroid stimulating hormone (TSH; iIU/ml); serum thyroxine (T4; /g/dL); 000135 3M Company Page 4 of 121 free thyroxine (free T4; ng/dL); serum triiodothyronine (T3; pg/mL); thyroid hormone binding ratio (THBR, %, previously referred to as T3 Uptake) and free thyroxine index (FIT). Statistical analyses were conducted on the entire surveillance population as well as subgroups by gender, production worker (yes/no) and location. Univariate analyses categorized mean levels by serum PFOS quartile distributions. Multivariable regression was used to analyze the clinical chemistry and thyroid hormones as dependent variables in relation to the independent effects of PFOS, PFOA or TOF adjusted for several demographic variables (age, body mass index, number of alcoholic drinks per day, cigarettes smoked per day and years worked). There was a modest positive association between PFOS or PFOA with cholesterol as well as a stronger positive association between PFOA and triglycerides. These associations are inconsistent with the known toxicological evidence that has shown the hypolipidemic (not hyperlipidemic) effect of PFOS (in rats and primates) and PFOA (in rats but no effect in primates) at dosages that produced serum PFOS or PFOA levels higher than those measured in this population. Therefore, it is unlikely the observed positive associations between PFOS or PFOA and lipids are causal. Because of the potential confounding positive association with serum triglycerides, this variable was added to the hepatic clinical chemistry models as an independent variable. In these models, no significant associations were observed with PFOS, PFOA or TOF in relation to alkaline phosphatase, GGT, AST, ALT or total bilirubin. Although T3 was positively associated with PFOA, no other thyroid hormones were associated with PFOS, PFOA or TOF; thus there is unlikely a causal explanation (e.g., hypothyroidism or 000136 3M Company Page 5 of 121 hyperthyroidism) for this positive T3 association with PFOA. Hematological and urinalysis results were unremarkable. In summary, the findings from the 2000 fluorochemical medical surveillance program continue to suggest that Antwerp and Decatur fluorochemical production and non-production employees do not have significant changes in serum cholesterol, lipoproteins or hepatic enzymes that are consistent with toxicological findings in laboratory animals. Limitations of the study include its cross-sectional design, the voluntary participation rates and the lower levels of serum PFOS and PFOA measured among these employees compared with those suspected to cause effects in laboratory animals. A longitudinal analysis is reported separately for the fluorochemical medical surveillance Antwerp and Decatur program data from 1994 through 2000. 000137 INTRODUCTION 3M Company Page 6 of 121 The 3M fluorochemical medical surveillance program is conducted on a routine periodic basis at the company's Antwerp (Belgium) and Decatur (Alabama) fluorochemical manufacturing plants. Prior to 1994, total organic fluorine was measured rather than any specific fluorochemical analyte. Serum perfluorooctanesulfonate (PFOS) and periluorooctanoate (PFOA) have been routinely assayed since 1994/95 rather than total organic fluorine. An analysis of the 1994/95 and 1997 medical surveillance program data in relation to Antwerp and Decatur employees' serum PFOS levels have been reported elsewhere (Olsen et al, 1998a, 1999a). In the 1994/1995 medical surveillance program, a total of 178 employees participated (Antwerp = 88; Decatur = 90) and 149 employees participated in 1997 (Antwerp = 65; Decatur = 84). A total of 61 Antwerp and Decatur employees participated in both years. The Antwerp male employee population was significantly younger than that at Decatur, had lower Body Mass Indices (BMI) and had higher self-reported daily consumption of alcohol. In addition, the employees' clinical chemistry profiles were different for several tests. The Antwerp employee population had lower mean alkaline phosphatase and triglyceride values and higher total bilirubin and HDL values than the Decatur employee population. The findings from this prior epidemiologic analysis suggested that significant clinical chemistry and hematological abnormalities were not associated with serum perfluorooctanesulfonate (PFOS) levels up to 6 parts per million (Olsen et al 1998a; 1999a). Nor were there consistent associations reported between serum PFOS and several hormone tests including testosterone, estradiol and thyroid stimulating hormone (TSH). It was not possible to derive inferences from the few employees who had serum 000138 3M Company Page 7 of 121 PFOS levels > 6 ppm. An important limitation of this prior analysis was the low voluntary participation of male employees (less than 50%) and insufficient sample size of female employees which prevented a separate analysis. Also, although serum perfluorooctanoate (PFOA) was measured, it was not included in the analyses. Because the voluntary nature of the medical surveillance program may not provide for a complete understanding of the distribution of serum fluorochemical levels in the Decatur workforce, a random sample of 232 employees was selected for fluorochemical testing in the Fall, 1998. The distributions of employee serum PFOS and PFOA levels were comparable to the results reported in the voluntary Decatur medical surveillance program (Olsen et al 1999b). This finding suggested that the distribution of serum fluorochemical levels observed in the prior voluntary medical surveillance program likely reflected the distribution of serum PFOS and PFOA levels of all employees in the chemical plant. Detailed discussions of the toxicology and epidemiology of PFOS and PFOA have been reported elsewhere (3M Company 2000; Alexander 2001a; 2001b; Butenhoff et al 2001: Gilliland and Mandel 1993;1996; Haughom and Spydevold 1992; Olsen et al 1998a: 1998b; 1999a; 2000; Pastoor et al 1987; Seacat et al 2001a; 2001b; Sohlenius et al 1993). For the purpose of brevity, this information will not be summarized in this Introduction. Suffice it to mention that for the purpose of employee medical surveillance, PFOS has been reported to be an inducer of peroxisome proliferation and hypolipidemia in rodents (Pastoor et al 1987; Ikeda et al 1987; Haughom and Spydevold 1992; Seacat et al 2001a: Sohlenius et al 1993 ) and primates (Seacat et al 2001b). PFOA has been inconsistently reported to produce hypolipidemia in rodents (Pastoor et al 1987; 000139 3M Company Page 8 o f 121 Haughom and Spydevold 1992;) and not in primates (Butenhoff et al 2001). The mechanism of action pertaining to this hypolipidemia remains to be fully elucidated. The purpose of this report was to conduct a cross-sectional analysis of the 2000 fluorochemical medical surveillance program for Antwerp and Decatur male and female employees. Unlike the earlier report for Antwerp and Decatur employees which only analyzed for PFOS (Olsen et al 1998a; 1999a), the present study examined associations for both PFOS and/or PFOA as well as a calculated measure for total organic fluorine (TOF). Longitudinal analyses of employees who participated from 1994/95 through 2000 were not analyzed as this was a focus of a separate analytical report (Olsen et al 2001a). METHODS The fluorochemical medical surveillance program is available, on a voluntary basis, to all Antwerp and Decatur chemical plant employees and those site employees who may work in the chemical plant area. In 2000, approximately 340 Antwerp and 500 Decatur chemical plant and site employees were eligible to participate. In addition to the fluorochemical testing program, a standard battery of clinical chemistry, pulmonary function and urinalysis (Decatur only) tests were performed on employees. In addition, several thyroid hormones were measured. A site-specific work history was also administered to all employee participants. Analyses of these self-reported workplace questionnaire data in conjunction with the employees' serum fluorochemical levels have been reported elsewhere for Antwerp (Olsen et al 2001b) and Decatur (Olsen et al, 2001c). 000140 3M Company Page 9 of 121 Hematology. Clinical Chemistry and Urinalysis Allina 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/mm3), white blood cells (WBC, 1000/ mm3) and platelet count (1000/ mm3); and the following clinical chemistry tests: alkaline phosphatase (IU/L), gamma glutamyl transferase (GGT, IU/L), aspartate aminotransferase (AST, IU/L), alanine aminotransferase (ALT, IU/L), total and direct bilirubin (mg/dl), blood urea nitrogen (BUN, mg/dl), serum creatinine (mg/dl), blood glucose (mg/dl), cholesterol (mg/dl), high density cholesterol (HDL, mg/dl) and triglycerides (mg/dl). Urinalyses were only assessed for Decatur employees via the standard urine microstick analysis which tested for urine glucose, albumin and red blood cells. Thyroid Hormones Six thyroid tests were conducted by LabCorp (Kansas City, MO): thyroid stimulating hormone (TSH; /IU/ml); serum thyroxine (T4; /g/dL); free thyroxine (free T4; ng/dL); serum triiodothyronine (T3; pg/mL); thyroid hormone binding ratio (THBR, %, previously referred to as T3 Uptake) and free thyroxine index (FTI). TSH, free T4 and T3 were determined by an immunochemiluminometric assay (ICMA). T4 and THBR were determined by a cloned enzyme donor immunoassay (CEDIA). FTI was calculated by multiplying T4 and THBR. 000141 3M Company Page 10 o f 121 Fluorochemical Analyses Sera samples were extracted using an ion-pairing extraction procedure (Hansen et al, 2001). The extracts were quantitatively analyzed for PFOS (perfluorooctanesulfonate), PFOA (perfluorooctanoate), PFHS (perfluorohexanesulfonate), PFOSAA (N-ethyl perfluorooctanesulfonamidoacetate), M570 (N-methyl perfluorooctanesulfonamidoacetate), PFOSA (perfluorooctanesulfonateamide) and M556 (perfluorooctariesulfonamidoacetate) using high-pressure liquid chromatography/electrospray tandem mass spectrometry (HPLC/ESMSMS) and evaluated versus an extracted curve from a human serum matrix. Endogenous levels of certain fluorochemical were determined in the standard serum matrix and additional fluorochemical was spiked into the matrix. The total amount of each specific fluorochemical (endogenous + spiked) was used to construct an extracted standard curve. All serum fluorochemical analyses were determined by Northwest Bioanaltyical Laboratory Inc. (Salt Lake City, UT). A description of the distribution of the serum fluorochemical levels is reported elsewhere for Antwerp (Olsen et al, 2001b) and Decatur (Olsen et al, 2001c). For Antwerp, all employee serum values for PFOS and PFOA values were above the lower limit of quantitation (LLOQ). There was one employee (0.3 percent) with a PFHS value below the LLOQ (0.0027 ppm) and one employee (0.3 percent) with a M570 below the LLOQ (0.0057 ppm). There were 111 employees (44 percent) with PFOSAA values below the LLOQ (0.006 ppm); 88 employees (35 percent) were below the LLOQ (0.001 ppm) for PFOSA; and 13 employees (5 percent) were below the LLOQ (0.0043 000142 3M Company Page 11 of 121 ppm) for M556. For Decatur, all employee serum values for PFOS, PFHS, PFOA and M570 were above the respective lower limit of quantitation (LLOQ). There were 8 (3 percent) employees with PFOSAA values below the LLOQ (0.006 ppm); 111 employees (42 percent) were below the LLOQ for PFOSA (0.001 ppm); and 13 employees (5 percent) were below the LLOQ for M556 (0.0043 ppm). For statistical analysis purposes, serum fluorochemical values that were less than the LLOQ were assumed to be the midpoint between zero and the LLOQ. A total organic fluorine index (TOF) was determined by calculating the percent of each specific fluorochemical's molecular weight that was attributed to organic fluorine (PFOS (64.7%); PFHS (61.9%); PFOA (69.0%); PFOSAA (55.3%); PFOSA (64.7%); M570 (56.6%) and M556 (58.1%)) multiplied by the ppm measured for each fluorochemical and then summed across all seven fluorochemicals. Data Analyses Serum PFOS and PFOA levels were the predominant fluorochemicals as the other five analytes were measured at considerably lower levels (Olsen et al 2001b; 2001c); therefore. PFOS and PFOA were the only two specific fluorochemicals analyzed as explanatory variables in regression models." TOF was also considered in the analyses which took into account these other analytes in an aggregate index (see above definition). Descriptive simple and stratified analyses, Pearson correlation coefficients, ANOVA and multivariable regression were used to evaluate associations between PFOS, PFOA and TOF and each hematological and clinical chemistry test and thyroid hormone assay. For stratified analyses, employees were divided into quartiles of their serum PFOS 000143 3M Company Page 12 of 121 distribution. Age, body mass index, current alcohol consumption (drinks per day) and cigarette use (cigarettes smoked per day), years worked at Antwerp or Decatur, and type of job (production versus non-production) were potential confounding factors that were considered in the analyses. Production jobs included cell operators, chemical operators, mill operators and crew supervisors. Non-production jobs included engineers, QA/AC laboratory and research workers, secretaries and managers. Multivariable regression models were fitted with PFOS and/or PFOA analyzed as a continuous variable(s). Significance of coefficients was considered at p < .05. Natural log transformations of the dependent variables were performed, when necessary, to normalize variables and to enhance model fit. Study results were analyzed using the SAS System (1990). RESULTS Altogether, there were 255 Antwerp employees (206 male and 49 female) and 263 Decatur employees (215 male. 48 female) who participated in the 2000 fluorochemical medical surveillance program (Table 1). Seventy three percent of the Antwerp male employees and 75 percent of the Decatur employees worked in production activities. Only 12 percent of the Antwerp female employees worked in production activities compared to 63 percent of the Decatur female employees. Provided in Table 2 are the mean PFOS, PFOA and TOF values, demographic values and clinical chemistry and thyroid values for male employees stratified by location and production or non-production work activities. Regardless of the production categorization, Antwerp male employees compared to Decatur employees had lower 000144 3M Company Page 13 of 121 serum PFOS and PFOA levels; were significantly younger; had lower mean BMIs; worked fewer years; drank, on average, more alcoholic beverages per day; had higher mean HDL and total bilirubin values; and had lower mean triglyceride, alkaline phosphatase, GGT, AST and ALT values. Mean thyroid hormone values tended to be higher among Antwerp employees. All mean values were within reference ranges. Comparable findings were observed for Antwerp female employees compared to Decatur female employees (Table 3). Given the differences between Antwerp and Decatur employees, univariate analyses were initially stratified by location. Antwerp data, stratified by gender and production, are provided in Tables 4 through 12. In a similar fashion Decatur employee data are provided in Tables 13-24. The Decatur data also include employee urinalysis results. Antwerp production male employee data (n = 150), stratified by quartile of serum PFOS distribution, is presented in three sequential tables for clinical chemistry (Table 4) and thyroid hormones (Table 5) and hematology (Table 6) results. The highest quartile (4th) mean serum PFOS level was 2.61 ppm (range 1.76 - 6.24 ppm) compared to the lowest quartile (1st) mean serum PFOS level of 0.29 ppm (range 0.04 - 0.41 ppm). Production workers in the highest quartile of serum PFOS levels were older and worked more years at Antwerp. There were no significant mean differences between the quartiles for BMI, cigarettes smoked or drinks per day. There was only one significant difference between the four quartile levels for any clinical chemistry, thyroid hormone or hematology comparisons. This significant difference was the comparison of the mean BUN value between the 1st and 3rd quartiles. 000145 3M Company Page 14 of 121 In a similar fashion for the 56 non-production Antwerp male employees, their clinical chemistry, thyroid hormone and hematology results are presented in Tables 7, 8 and 9, respectively, for their quartile distribution of serum PFOS. In this analysis, the highest quartile had a mean serum PFOS level of 0.90 ppm (range 0.49 - 1.76) compared to a mean of 0.13 ppm (range 0.05-0.20 ppm) in the lowest quartile. No significant mean differences were observed for demographic (Table 7), clinical chemistry (Table 7), thyroid hormone (Table 8) or hematology (Table 9) comparisons between the serum PFOS quartile distributions. Among the 49 Antwerp production and non-production female employees analyzed as a group (Table 10), the highest quartile mean serum PFOS level was 0.26 ppm (range 0.15 - 0.55) compared to the lowest quartile mean serum PFOS level of 0.06 ppm (range 0.04 - 0.08 ppm). The highest serum PFOS quartile did not significantly differ demographically than the other three quartiles (Table 10). The lower three quartiles had some significant differences between themselves for the mean comparisons of years worked and drinks per day. Only one clinical chemistry. BUN, was significantly different between the quartiles as the 3rd and 4thquartiles had higher mean BUN values than the U*quartile. All mean values were within reference ranges. No significant mean thyroid hormone (Table 11) or hematology (Table 12) difference was observed between the quartiles. A total of 161 Decatur production male employees were stratified based on their quartile distribution of serum PFOS (Table 13). The highest quartile had a 3.22 ppm mean serum PFOS level (range 2.31 -10.06) compared to 0.55 ppm mean serum PFOS level in the lowest quartile. There were no significant mean demographic differences 000146 3M Company Page 15 o f 121 between the four quartiles and the only clinical chemistry test that was significantly different was ALT (Table 13). The highest quartile had a significantly higher mean ALT level (44 IU/ml) compared to the 1st (33 IU/ml), 2nd (32 IU/ml) or 3rd (33 IU/ml) quartiles. There were no significant mean differences for the Decatur male production employee quartile distributions for thyroid hormones (Table 14), hematology (Table 15) or urinalysis (Table 16) results. Among the 54 Decatur non-production male employees (Table 17), their highest quartile mean serum PFOS level was 1.66 ppm (range 1.00 - 2.95 ppm) compared to the lowest quartile mean of 0.19 ppm (range 0.06 - 0.29 ppm). The highest quartile worked almost twice as long as the lowest quartile (Table 17). There were no significant differences in other demographics, clinical chemistries (Table 17), thyroid hormones (Table 18), hematology (Table 19) or urinalysis (Table 20) results among the quartile distributions. Among the 48 Decatur production and non-production female employees (Table 21), the highest quartile had a mean serum PFOS level of 2.04 ppm (range 1.38 - 3.62 ppm) compared to the lowest quartile mean serum PFOS level of 0.20 ppm (range 0.06 0.31 ppm). There were no significant differences between the quartiles in relation to demographics (Table 21), clinical chemistries (Table 21) or thyroid hormones (Table 22). The third quartile had a significantly lower mean platelet count than the 1st quartile (Table 23); however, the fourth quartile was not significantly lower than the 1st quartile. Urinalysis findings did not differ by quartile (Table 24). Presented in Table 25 are the number (and percentage) of Antwerp or Decatur employees which had above reference range values for hepatic clinical chemistry tests. 000147 3M Company Page 16 of 121 These findings in Table 25 are stratified by serum PFOS quartile distribution within each of the gender and production/non-production categories. Because each sub-population has a different serum PFOS quartile distribution, comparisons should only be done within each location-, production- and gender-specific category. Also presented is the number and percentage of employees who had one or more liver enzyme and bilirubin tests above the reference ranges (see aggregate total liver panel). The percentage of Antwerp employees whose liver enzyme tests were above reference range values was comparable for production and non-production male employees. Among Decatur employees, there was a higher percentage of production male employees in the 4th quartile for ALT, GGT and the total liver panel than the other quartiles. For non-production male employees, the highest percentages occurred in the second or third quartiles. Neither Antwerp or Decatur female employees had percentages consistent with any trend in the quartile distributions. Provided in Tables 26 and 27 are the serum PFOS quartile distributions for the combined 421 Antwerp and Decatur production and non-production male employees. The highest quartile (4th) had a mean serum distribution of 2.69 ppm (range 1.69 - 10.06 ppm) compared to 0.27 ppm mean (range 0.04 - 0.42 ppm) compared to the lowest ( l5*) quartile distribution. It is important to note that the number (and percentages) of Antwerp versus Decatur employees in each of these four quartiles differ (see footnote to Table 26). In the lowest (1st) quartile, there is a greater percentage of Antwerp than Decatur male employees and more non-production than production employees. In the subsequent higher serum PFOS quartiles, the percentage of Decatur production male employees increased and the percentage of non-production male employees, whether 000148 3M Company Page 17 of 121 from Antwerp or Decatur, decreased. These differences were also reflected in the demographics between quartiles. For example, demographically the trend from the lowest to highest quartile increased with age, BMI and years worked and decreased with the mean number of alcohol drinks per day. Likewise, the means of the clinical chemistry and thyroid hormone tests were reflective of the higher percentage of Antwerp employees in the lower quartiles and higher percentage of Decatur employees in the higher quartiles. Mean triglyceride and alkaline phosphatase levels were lower and total bilirubin levels were higher in the lowest quartile compared to the highest quartile. For thyroid hormones, T3 was lower in the 1st quartile compared to the 4th quartile and THBR was significantly higher. Combined analyses of Antwerp and Decatur production and non-production female employees (Tables 28 and 29) presented a similar distribution of employees by location and production pattern as was observed with the production and non-production male employees (Tables 26 and 27). Antwerp female employees predominated in the lowest quartile and Decatur female employees predominated in the highest quartile. This distribution difference is then seen with the lower mean age, BMI and alkaline phosphatase findings and the greater number of drinks per day and higher total bilirubin levels in the lowest quartile compared to the highest quartile. Also observed was a lower mean GGT and blood glucose level in the lowest quartile when compared to the highest quartile. There were no thyroid hormone differences between the quartile distributions (Table 29). Summarized in Table 30 are the combined number of Antwerp and Decatur employees (and percentages) who had hepatic clinical chemistry tests above reference 000149 3M Company Page 18 of 121 range values stratified by quartile of the serum PFOS distribution. Among male employees, twelve percent of the employees had above reference range values for ALT and GGT in the 4thquartile compared to 4 to 8 percent in the 1st through 3rdquartiles. For the total liver panel, 23 percent of the male employees had one or more liver clinical chemistry tests above the reference range value compared to 14 to 16 percent in the lower three quartiles. No differences were observed within the female employee population. These percentages were not adjusted for potential confounding factors (e.g., BMI). Because the higher liver enzyme function test results in the 4thquartile might be confounded by demographics (higher BMI, older age) and/or clinical chemistry tests (triglycerides) reflective of dietary differences, multivariable regression analyses were conducted on the combined Antwerp and Decatur male employee participants. Each regression model had the following variables: production job (yes = 1; no = 0); Antwerp/Decatur (1 = Antwerp; 0 = Decatur); age, BMI, cigarettes per day, drinks per day and years worked. For the analyses that involved hepatic clinical chemistry tests, triglycerides was also considered a potential explanatory variable. Regression models analyzed serum PFOS, serum PFOA, serum PFOS and PFOA, and total organic fluorine (TOF). Provided in tables 31 through 34 are the analyses for these fluorochemical comparisons in relation to their effect on cholesterol, adjusted for the other explanatory variables. Serum PFOS was positively associated with cholesterol although its explanation of the variability of cholesterol in the model was less than 1 percent (see partial R:). (Note: This positive association is opposite that of the well-established negative association between serum cholesterol and PFOS that have been shown to occur 000150 3M Company Page 19 of 121 in toxicological studies at threshold serum doses that were approximately 2 orders of magnitude higher than those serum PFOS levels observed in these employees.) Like PFOS (Table 31), there were positive significant associations each for PFOA (Table 32) and TOF (Table 34) with cholesterol but the model that jointly examined the effects of PFOS and PFOA found neither to be significant (Table 33). Again, this is contrary to the toxicological research that has shown PFOA lowers serum cholesterol. Age and drinks per day were significant variables in the model with cholesterol. PFOS and TOF were not significantly associated with HDL, but PFOA was significantly negatively associated (Tables 35 through 38). As to be expected, BMI and drinks per day were strongly associated with HDL. Analysis of triglycerides showed PFOS, PFOA and TOF were positively associated (Tables 39 through 42). PFOA appeared to be the more significant predictor than PFOS. (Note: PFOS and PFOA have decreased serum triglyceride levels at toxicological doses, not increased serum triglyceride levels.) Age, BMI and cigarettes smoked per day were significant variables in the triglyceride models found in Tables 39 through 42. Provided in Figures 1 through 3 are scatter plots of the simple linear regressions between the natural log of serum triglycerides and PFOA for Antwerp male, Decatur male and Antwerp and Decatur female employees. Multivariable regression model results for the hepatic clinical chemistry analyses are found in Tables 43 through 62. Because of the potential confounding positive association with serum triglycerides, this variable is added to these models. No significant associations were observed with PFOS, PFOA and TOF in relation to alkaline phosphatase (Tables 43 through 46), GGT (Tables 47 through 50) or AST (Tables 51 through 54). Although PFOS or PFOA were not significantly associated with ALT oooisi 3M Company Page 20 of 121 (Tables 55 - 57), TOF was positively associated with ALT (Table 58). PFOS, PFOA or TOF were not significant predictors of total bilirubin (Tables 59-62). Multivariable regression analyses of the thyroid hormones resulted in no significant associations of PFOS, PFOA or TOF with TSH (Tables 63 - 66), T4 (Tables 67 - 70), Free T4 (Tables 71 - 74), THBR (Tables 75 - 78) orFTI (Tables 79 - 82). PFOS, PFOA and TOF were positively associated with T3 although contributed minimally to the variation explained in the model (see partial R2). DISCUSSION Although voluntary participation rates ranged from 53 percent (Decatur) to 75 percent (Antwerp), the 2000 fluorochemical medical surveillance program had the most (in absolute numbers) employee male and female participants ever for both locations. This is likely due to a combination of factors including 1) greater knowledge of the collective (individual and research) value of the fluorochemical medical surveillance program; 2) employee awareness about the persistence and prevalence of PFOS in human tissue and the environment; and 3) the company's May 16, 2000 phase out announcement that it would cease production of perfluorooctanyl chemistry in certain repellents and surfactants by the end of 2000. Serum PFOS and PFOA levels were comparable to those previously reported for employees at these manufacturing operations. Serum levels appeared to be log normally distributed with the highest values for PFOS at 10 ppm. This upper tail of the serum PFOS distribution was also reported in a random sample analysis of Decatur employees conducted in 1998 (Olsen et al 1999b). Separate reports examine the employees' serum 0001S2 3M Company Page 21 o f 121 PFOS, PFOA, PFHS, PFOSAA, M570, PFOSA and M556 levels measured in the 2000 fluorochemical medical surveillance program with their workplace operations in Antwerp (Olsen et al, 2001b) and Decatur (Olsen et al, 2001c). We continued to observe consistent differences between Antwerp and Decatur employees regarding their demographics and lifestyle differences. In particular, Antwerp male employees, on average, were younger (and thus worked less), had much lower BMIs and drank more alcoholic beverages than their Decatur counterparts. All three differences can be important confounding variables when analyzing lipid and hepatic clinical chemistry tests. We have also consistently seen higher total bilirubin values among Antwerp employees since 1995 which may be partially attributable to a greater prevalence of Gilbert's syndrome (Olsen et al 1998a; 1999a). An inconsistent finding from these aggregate analyses was the positive associations in the multivariable models reported between PFOS and serum cholesterol and PFOA and serum cholesterol and triglycerides. There is a substantial body of toxicological literature to suggest these associations are spurious because PFOS (in rats and primates) has been reported to decrease serum cholesterol and triglyceride levels (3M Company 2000; Haughom and Spydevold 1992; Ikeda et al 1987; Pastoor et al 1987; Seacat et al 2001a; 2001b; Sohlenius et al 1993). On the other hand, there is inconsistent evidence for hvpolipidemia with PFOA in rodents (Pastoor et al 1987; Haughom and Spydevold 1992) and no effect observed in primates (Butenhoff et al 2001). In primates, there was no association observed between PFOA and cholesterol or triglycerides (Butenhoff et al 2001). There is no toxicological evidence that at the serum PFOA levels observed in our medical surveillance program that PFOA would have resulted in 000153 3M Company Page 22 of 121 hyperlipidemic associations. In addition, the PFOA levels observed among Antwerp and Decatur employees in 2000 was lower than those measured in 3M's Cottage Grove manufacturing employees whose serum PFOA levels have been assayed as high as 100 ppm. Hypolipidemic or hyperlipidemic effects have not been associated with serum PFOA levels among these Cottage Grove employees (Gilliland and Mandel 1996; Olsen et al, 2000). Most recently, the 2000 Cottage Grove fluorochemical medical surveillance program analysis again showed no association between serum PFOA levels and serum cholesterol or triglycerides (as seen in Figure 4). (Note: The serum PFOA levels graphed in Figure 4 are substantially higher than those cited in Figures 1 through 3 for the Antwerp and Decatur male and female employees.) We therefore believe that it is highly unlikely that these are causal associations observed in the 2000 fluorochemical medical surveillance data between PFOA and serum cholesterol and triglycerides. Previous toxicological and epidemiological research has also not suggested positive associations between elevated serum liver enzymes results and serum PFOS or PFOA that were at the levels observed in the Antwerp and Decatur employee population (3M Company, 2000; Butenhoff et al 2001; Gilliland and Mandel 1996: Olsen et al 1998a; 1999a; 2000; Seacat et al 2001a; 2001b). In this 2000 fluorochemical medical surveillance program we observed, among Decatur production employees, a significantly greater mean ALT among those workers in the highest serum PFOS quartile distribution compared to the other three quartiles. This highest quartile of Decatur employees also had the greatest percentage of employees with ALT (28%) and GGT (15%) values above the reference range as well as the total liver panel (35%). A comparable percentage (36%) was observed among Decatur non-production employees in the second lowest 000154 3M Company Page 23 of 121 quartile with one or more hepatic clinical chemistry tests above the reference range. When male employees were combined by production status and location (as seen in Table 30), we reported an upward trend in the percentage of employees in the highest quartile with values above the reference range for ALT (12%), GGT (12%) and total liver panel (23%). However, after adjusting the employees' individual liver function values by potential confounding factors including age, BMI, number of alcoholic drinks per day, cigarettes per day and serum triglyceride values, we found no association between liver function values and PFOS or PFOA. We therefore suspect that the univariate associations were influenced by known confounders of liver function analyses A battery of thyroid hormone tests were included in the 2000 fluorochemical medical surveillance program due to preliminary, albeit biologically inconsistent, findings in toxicological studies that have yet to be completed. Our surveillance data do not suggest any biologically significant associations between thyroid hormones and employees' measured serum PFOS, PFOA or calculated TOF levels. A retrospective cohort mortality study of Decatur employees from 1961-1997 reported 3 deaths from bladder cancer compared to 0.2 expected in the subgroup of workers with the highest potential exposure to perfluorooctanesulfonyl fluoride (POSF)based chemistry and materials (Alexander 2001b). It was not determined whether this association was fluorochemical-related or possibly due to other non-fluorochemical occupational or non-occupational exposures. An analysis of episode of cares (Olsen et al 2001d) reported a higher reoccurrence of cystitis among female Decatur chemical plant workers than their counterparts in the film plant although the actual prevalence of unique individuals with episodes of care regarding cystitis was similar. No differences were 000155 3M Company Page 24 of 121 reported among male chemical and film plant employees. The analysis of these 2000 fluorochemical medical surveillance data showed no association between the prevalence of abnormal urinalyses and employee serum PFOS levels among the Decatur employees. Limitations of this study design include its cross-sectional nature which does not adequately allow for the assessment of temporal changes. However, the large participation of employees in 2000 who may have participated in the 1994/95 and/or 1997 fluorochemical medical surveillance programs at these two manufacturing sites has enabled a longitudinal analysis to be performed. This longitudinal analysis is the focus of a separate 3M investigation (Olsen et al, 2001a). Although still very limited in numbers, we were able to provide separate cross-sectional analyses for female employees, for the first time, which showed no biologically relevant associations between serum PFOS and/or PFOA levels with clinical chemistries, thyroid hormones or hematology results. Because 3M has announced a phase-out of the production of perfluorooctanyl chemistryrelated materials, we anticipate that the Antwerp and Decatur employee population mean PFOS and PFOA serum levels should be lower when measured during the next fluorochemical medical surveillance program. These future analyses may be hindered by the fewer employees in the workforce as a consequence of the phase-out announced by the company. Another study limitation was the lower serum PFOS and PFOA levels measured among these employees compared with those suspected to cause effects in laboratory animals. In summary, the findings from the 2000 fluorochemical medical surveillance program continue to suggest that Antwerp and Decatur fluorochemical production and non-production employees do not show substantial changes in serum hepatic enzymes, 000156 3M Company Page 25 of 121 cholesterol, or lipoproteins associated with the serum PFOS and PFOA levels measured. A separate longitudinal analysis is reported for the fluorochemical medical surveillance Antwerp and Decatur program data from 1994 through 2000. ACKNOWLEDGEMENTS The investigators acknowledge the contributions of Kimberly Young in the prepartion of this report. 000157 3M Company Page 26 of 121 REFERENCES 3M Company (2000). SEDS Initial assessment repot: Perfluorooctane sulfonic acid and its salts. St. Paul (MN):3M Company, (unpublished report). Alexander BH (2001a). Mortality study of workers employed at the 3M Cottage Grove facility. Minneapolis (MN)rUniversity of Minnesota, (unpublished report). Alexander BH (2001b). Mortality study of workers employed at the 3M Decatur facility. Minneapolis (MN):University of Minnesota, (unpublished report). Butenhoff JL, Costa G, Elcombe C, Farrar D, Hansen K, Iwai H, Jung R, Kennedy G, Lieder P, Olsen GW, Thomford P. Toxicity of ammonium perfluorooctanoate (APFO) in cynomolgus monkeys after 26 weeks of oral dosing. St. Paul (MN):3M Company, (unpublished report) Gilliland FD, Mandel JS (1993). Mortality among employees of a perfluorooctanoic acid production plant. J Occup Med 35:950-954. Gilliland FD, Mandel JS (1996). Serum perfluorooctanoic acid and hepatic enzymes, lipoproteins and cholesterol: a study of occupationally exposed men. Am J Ind Med 129:560-568. Hansen KJ, Clemen LA, Ellefson ME, Johnson JHO (2001). Compound-specific, quantitative characterization of organic fluorochemicals in biological matrices. Environ Sei Technol 35:766-770. Haughom B, Spydevold O ( 1992). The mechanism underlying the hypolipmie effect of perfluooctanoic acid (PFOA), perfluoroctanesulphonic acid (PFOSA) and clofibric acid. Biochemica et Biophysica Acta 1128:65-72. Ikeda T. Fukuda K, Mori I, Enomoto M, Komai T, Suga T (1987). Induction of cytochrome P-450 and peroixome proliferation in rat liver by perfluorinated octanesulfonic acid. In: Perixosmes in Biology and Medicine. (HD Fahmi and H Sies, eds) New York:Springer Verlag, pp 304-308. Olsen GW. Burris JM, Mandel JH, Zobel LR (1998a). An epidemiologic investigation of clinical chemistries, hematology and hormones in relation to serum levels of perfluorooctane sulfonate in male fluorochemical production employees. St. Paul:3M Company (unpublished report). Olsen GW, Gilliland FD, Burlew MM, Burris JM, Mandel JS, Mandel JH (1998b). An epidemiologic investigation of reproductive hormones in men with occupational exposure to perfluorooctanoic acid. JOEM (40(7):614-621. 000158 3M Company Page 27 of 121 Olsen GW, Burris JM, Mandel JH, Zobel LR (1999a). Serum perfluorooctane sulfonate and hepatic and lipid clinical chemistry tests in fluorochemical production employees. JOEM 41(9):799-806. Olsen GW, Logan PW, Simpson CA, Hansen KJ, Burris JM, Burlew MM, Schumpert JC, Mandel JH (1999b). Fluorochemical exposure assessment of Decatur chemical and film plant employees. St. Paul:3M Company (unpublished report). Olsen GW, Burris JM, Burlew MM, Mandel JH (2000). Plasma cholecystokinn and hepatic enzymes, cholesterol and lipoproteins in ammonium perfluorooctanoate production workers. Drug Chem Toxicol 23(4):603-620. Olsen GW, Burlew MM, Burris JB, Mandel JM (2001a). A longitudinal analysis of serum perlfuorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) levels in relation to lipid and clinical chemistry test results from male employee participants of the 1994/95,1997 and 2000 fluorochemical medical surveillance program. St. Paul, MN:3M Company (unpublished report). Olsen GW, Schmickler MN, Tierens JM, Logan PW, Burris JM, Burlew MM, Lundberg JK. Mandel JH (2001b). Descriptive summary of serum fluorochemical levels among employee participants of the year 2000 Antwerp fluorochemical medical surveillance program. St. Paul:3M Company (unpublished report). Olsen GW, Logan PW, Simpson CA, Burris JM, Burlew MM, Lundberg JK, Mandel JH (2001c). Descriptive summary of serum fluorochemical levels among employee participants of the year 2000 Decatur fluorochemical medical surveillance program. St Paul:3M Company (unpublished report). Olsen GW, Burlew MM, Hocking BB, Skratt JC, Burris JM, Mandel JH (200Id). An epidemiologic analysis of episodes of care of 3M Decatur chemical and film plant employees. 1993-1998. St. Paul MN:3M Company (unpublished report). Pastoor TP, Lee KP, Pern MA, Gillies PJ (1987). Biochemical and morphological studies of ammonium perfluorooctnoate-induced hepatomegaly and peroxisome proliferation. Exp Mol Pathol 47:98-109. SAS Institute, Inc. (1990). SAS Users Guide:Statistics Version 6. Cary, NC:SAS Institute Inc. Seacat AM, Thomford PJ, Hansen KJ, Clemen LA, Case MT, Butenhoff JL (2001a). Sub-chronic dietary toxicity of potassium perfluorooctanesuifonic acid in rats. Toxicol Sci (submitted 2001a). Seacat AM, Thoford PJ, Hansen KJ, Olsen GW, Case MT, Butenhoff JL. Subchronic toxicity studies on perfluorooctanesulfonate potassium salt in cynomolgus monkeys. Toxicol Sci (submitted, 2001b). 000159 3M Company Page 28 o f 121 Sohlenius AK, Eriksson AM, Hogstrom C, Kimland M, DePierre JW (1993). Perfluorooctane sulfonic acid is a potent inducer of peroxisomal fatty acid B-oxidation and other activities known to be affected by peroxisome proliferators in mouse liver. Pharmacol Toxicol 72:90-93. 000160 Table 1 Number of employee Participants in the 2000 Antwerp and Decatur Medical Surveillance Programs 3M Company Page 29 o f 121 Antwerp (N = 255) Male (N = 206) Female (N = 49) Production Non-Production Production Non-Production 150(73)* 56(27)* 6(12)* 43 (88)* Decatur (N = 263) Male (N = 215) Female (N = 48) Production Non-Production Production Non-Production 161 (75)* 54 (25)* 30 (63)* 18(37)* *Percent in parenthesis 000161 PFOS PFOA TOP Age BMI Years Worked Cigarettes/day Drinks/day Cholesterol HDL Triglycerides Aik Phos GGT AST ALT Table 2 Mean Value for Male Employee Participants' Serum Fluorochemical Levels, Demographics, Clinical Chemistries and Thyroid Results 3M Company Page 30 o f 121 All Antwerp (N = 206) Decatur (N = 215) ().%d 1.40 1.03d 1.90 !.60d 2.65 37d 43 24.8d 28.8 13L 16 46 l.ld 0.1 218 215 55d 44 124" 191 60d 74 23d 31 23c 26 23d 35 Production Antwerp (N = 150) Decatur (N = 161) 1.16C 1.63 1.28" 2.34 i.97d 3.18 36d 42 24.6d 28.9 12* 15 56 l.ld 0.1 215 217 55d 43 124d 198 60d 76 23d 31 23d 26 22d 36 ___ Non-Production Antwerp (N = 56) Decatur (N = 54) 0.42b 0.73 0.34b 0.59 0.61b 1.07 Ocr 45 25.2d 28.4 15c 22 25 l.ld 0.2 225* 209 55c 45 122b 169 60* 67 26b 29 24 25 25 31 000162 Total Bilirubin Direct Bilirubin BUN Creatinine Glucose TSH T4 FreeT4 T3 THBR FTI 1.0" o .r I9d 1.2 85d 2.0" 8.2 l.r 131" 34d 2.7U a p < .05 compared to Decatur (t test) bp < .01 compared to Decatur (t test) c p < .001 compared to Decatur (t test) d p < .0001 compared to Decatur (t test) 0.7 0.1 15 1.1 95 2.9 8.4 1.1 125 31 2.5 Table 2 (continued) 1.0d 0.ib 19d l.ld 84d 2.0" 8.3 1.1* I32a 34d 2.7d 0.7 0.1 15 1.2 95 3.1 8.4 1.1 127 30 2.5 1. l d 0.1 19d 1.2 87" 1.9 8.1 1.1 126 35d 2.7" 3M Company Page 31 o f 121 0.8 0.1 15 1.1 94 2.2 8.5 1.1 120 31 2.5 000163 3M Company Page 32 of 121 Table 3 Mean Values for Female Employee Participants' Serum Fluorochemical Levels, Demographics, Clinical Chemistries and Thyroid Results PFOS PFOA TOF Age BMI Years Worked Cigarettes/day Drinks/day Cholesterol HDL Triglycerides Aik Phos GGT AST ALT Total Bilirubin Direct Bilirubin BUN Creatinine Glucose TSH T4 Free T4 T3 THBR FTI O' bocr Antwerp (N = 49) 0.13d 0.07d 0.17d 36 22.8d 12a 2d 0.5d 208 68a 94d 46a 12d 18 13d 0.1 16 0.9 85 2.3 10.2 l.lb 148b 30a 2.9d Decatur (N = 48) 0.93 1.23 1.76 42 27.7 13 5 0.1 200 59 133 65 18 20 19 0.6 0.1 12 0.8 87 2.3 9.3 1.0 128 28 2.5 a p < .05 compared to Decatur (student t test) bp < .01 compared to Decatur (student t test) c p < .001 compared to Decatur (student t test) dp < .0001 compared to Decatur (student t test) 0 0 0 16 4 Table 4 Antwerp Male Production Employee (N = 150) Fluorochemical, Demographic and Clinical Chemistry Results by Quartile of Serum PFOS Distribution 3M Company Page 33 o f 13 J PPOS Quartile 1 (N = 37) Mean Median SD Range 0.293*4 0.33 0 .1 1 0.04-0.41 PFOA 0.944 0.42 1.06 0.02-4.03 TOP 0.92214 0.60 0.78 0.05-3.03 Age 334 34 7 2 3 -4 8 BMI 24.3 23.8 2.7 19.2-33.2 Years Worked 8 r.3.4 5 6 2 - 25 Cigareltes/day 5 0 7 0 -2 0 Drinks/day 1 .2 1.0 1 0 -4 Cholesterol 207 2 0 2 39 145-308 Quarlile 2 (N = 38) Mean Median SD Range 0.583'4 0.57 0 . 1 2 0.41 -0 .7 8 1.51 0.72 1.70 0.07-7.04 J.63m 1.08 1.26 0.42-5.69 37 36 9 21 - 5 6 24.9 24.3 3.1 19.0-34.7 1 2 * II 9 2-29 5 08 0-25 1.1 0.9 1 .0 0 -4 216 217 41 148-295 Quartile 3 (N = 38) Mean Median SD Range I.18,A4 1.16 0 .2 2 0.79-1.66 1 .0 2 1 . 0 0 0.60 0.21 -3 .2 7 'j.821,4 1.80 0.55 1.03-3.14 37 36 9 22-55 25.0 25.3 2 .8 17.5-32.3 I21 13 7 1-29 40 6 0 -2 0 0.9 0.7 0.9 0 -4 212 196 41 105-297 Mean 2.61,AJ Quartile 4 (N = 37) Median SD Range 2.27 1.06 1.67-6.24 1 .6 6 ' 1.64 0.81 0.25-3.59 3.51,AJ 3.30 1.18 1.92-7.36 39' 39 8 28 - 55 24.3 24.7 3.0 17.8-30.9 15* 15 6 5 - 2 9 7 0 8 0-25 1.1 0.7 1 .2 0 -5 226 232 46 122-316 HDL 57 57 13 3 2 -8 5 52 49 1 0 3 8 -7 2 54 53 1 2 2 9 - 8 0 57 51 19 2 6 -1 1 9 Triglycerides 1 0 2 1 0 2 49 34 -2 2 1 125 113 87 35 - 546 140 113 124 4 1 -7 3 1 130 105 75 42 - 346 Aik Phos 60 61 15 3 4 -9 6 60 60 15 30-113 59 59 15 3 0 -9 4 61 62 14 2 1 -8 9 GOT 20 16 II 8 - 5 3 24 2 0 16 8-89 21 19 1 1 10-64 26 19 19 7-85 AST 24 24 8 1 3 -5 8 24 23 5 16-41 22 21 5 13-33 23 2 2 6 15-39 ALT 23 Total Bilirubin 1 .0 22 1 .0 10 11-71 0.3 0 .6 - 1 .6 22 1 .0 21 8 10-43 0.9 0.4 0 . 5 - 2 . 0 22 20 9 9-46 1 .0 1 .0 0.3 0 .5 -2 .3 20 1 .0 20 9 8-45 0.9 0.3 0 . 4 - 2 . 2 Direct Bilirubin 0 .1 0 . 1 0.04 0 . 0 - 0 . 2 0 . 1 0.1 0 .1 0.0-0.3 0 .1 0 .1 0.03 0 .0 - 0 .2 0 .1 0.1 0 .1 0.0-0.4 BUN I8 3 17 4 1 1 -2 5 18 18 4 12-25 2 0 * 19 5 14-31 19 19 4 1 1 -3 0 Creatinine 1.1 1 .1 0 . 2 0 .9 - 1.5 1 .1 1.1 0 .2 0.8-1.7 . -1 .1 1 .1 0 . 2 0 8 2 . 0 1.1 1.0 0 .2 0.8-1.5 Glucose 85 87 19 31 - 131 8 6 8 8 16 49-113 84 85 2 1 4 5 - 168 80 83 2 0 40-120 1 Mean is significantly different (P < .OS, Bunfemmi (Dunn) t test) from the mean of thelu quartile 3 Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from die mean of Ihe2'"1 quarlile 3 Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from the mean of the3^ quarlile {\n r \A 000165 ' Table 5 Antwerp Male Production Employee (N = 150) Thyroid Results* by Quartile of Serum PFOS Distribution** 3M Company Page 34 o f 121 TSH T4 FreeT4 T3 THBR FTI Quartile | (N = 37) Mean Median SD Range 1 .8 1 .6 1 .1 05 - 5.7 8 . 2 8.3 1.5 5 .4 - 1 1 .5 1 . 2 1 .1 0 . 2 0 . 9 - 1.5 127 127 15 9 5 - 1 5 5 34 34 3 28-40 2 . 8 2 . 6 0.5 2 . 1 - 4 . 2 Quartile 2 (N = 38) Mean Median SD Range 2 . 0 2 . 0 0.9 0 .7 - 5 .5 8.5 8 . 6 1.4 6 .6 - 1 2 . 0 1 .1 I.l 0 .1 0.9 - 1 .4 134 132 17 102-169 34 34 2 2 9 -3 9 2 . 8 2 . 8 0.4 2 . 1 - 4 . 0 Quartile 3 (N = 38) Mean Median SD Range 2 . 0 1.7 1 . 1 0 .8 - 6 . 1 8 . 2 8 . 1 1.4 5 . 0 - 11.5 . -1 .1 1 . 1 0 . 2 0 6 1 . 6 132 132 19 9 7 - 1 8 0 34 34 3 2 9 - 4 3 2.7 2.7 0.4 1 .9 -3 .9 Quartile 4 (N = 37) Mean Median SD Range 2 . 2 1 . 6 3.0 0.5 - 19.4 8 . 1 8 . 2 1.4 4 . 7 - 1 1 . 0 . -1 . 1 1 . 1 0 . 2 0 8 1 . 6 136 137 2 2 9 8 - 1 8 5 34 34 2 2 9 - 4 1 2.7 2.7 0.4 1 .6 -3 .6 *No significantly different (I* < .05, Bonferroni (Dunn) t test) mean values **See Table 4'for serum PFOS quartile distribution p o o i(z r . Table 6 Antwerp Male Production Employee (N = 150) Hematology Results* by Quartile of Serum PFOS Distribution** 3M Company Page 35 of 121 HCT HGB RBC WBC Platelets Quartile 1 (N = 37) Mean Median SD Range 46 46 3 41 - 5 3 15.5 15.4 0 . 8 1 4 .0 - 17.4 5.2 5.2 0.3 4 .6 - 5 .9 7.0 6.4 1 .8 4 .2 - 1 1 .4 244 242 57 1 3 8 -3 8 0 Quartile 2 (N = 38) Mean Median SD Range 46 46 3 39-51 15.5 15.5 0.9 1 3 .2 -1 8 .1 5.1 5.2 0.3 4 .4 - 5 .9 7.3 7.1 1 . 8 4 .4 - 1 1 .5 254 250 51 167-373 Quartile 3 (N = 37) Mean Median SD Range 46 46 3 4 0 -5 1 15.4 15.5 0 . 8 1 3 .6 - 17.3 5.1 5.1 0.3 4.7 - 5.9 7.6 7.4 1 .6 5 .2 -1 1 .1 253 242 ,73 106 - 427 Quartile 4 (N = 37) Mean Median SD Range 46 46 3 4 1 -5 1 15.3 15.3 0.9 1 3 .4 -1 7 .1 OO 1 5.0 5.0 0.3 7.2 6.9 2 .1 4.5 - 15.6 249 247 55 1 3 7 -3 6 9 *No significantly different (P < .05, Bonferroni (Dunn) t test) mean values **See Table 4 for serum PFOS quartile distribution 0 !S 7 Table 7 Antwerp Male Non-Production Employee (N = 56) Fluorochemical, Demographic and Clinical Chemistry Results by Quartile of Serum PFOS Distribution 3M Company Page 36 of 121 PFOS PFOA TOP Age BMI Quartile 1 (N = 14) Mean Median SD Range 0.133'4 0.13 0.05 0 .05-0.20 0 .I8 4 0.06 0.46 0.01 - 1.78 0.243'4 0.17 0.34 0 .0 6 - 1.38 40 36 13 2.3- 58 24.6 25.1 3.3 19.9-31.3 Mean 0.274 Quartile 2 (N = 13) Median SD Range 0.28 0.03 0 .2 1 -0.31 0.I94 0.15 0.13 0.05-0.51 0.374 0.35 0 .1 1 0 .22-0.64 41 42 6 31-53 25.4 24.3 3.3 21.7-34.2 Quartile 3 (N = 15) Mean Median SD Range 0.40*1'4 0.41 0.05 0.32-0.48 0.37 0.32 0.23 0.06-0.85 0.604 0.54 0.19 0.37-0.96 38 40 9 2 5 -5 6 26.1 25.1 3.5 21.1-33.9 Quartile 4 (N = 14) Mean Median SD Range 0.901,2,3 0.64 0.47 0 .4 9 -1 .7 6 0.62u 0.42 0.49 0.12-1.78 1.2 2 UJ 1.09 0.69 0.56-3.01 40 41 9 2 6 - 5 5 24.4 24.2 3.0 20.4-30.1 Years Worked 15 15 1 0 1-29 17 16 6 6-29 13 13 8 3-26 15 15 9 2 - 2 7 Cigarettes/day 1 0 5 0 -2 0 0 00 0 -0 40 7 0 -2 0 2 0 4 0 -1 0 Drmks/day I t 0.7 0.9 0.1 -2 .9 1 .0 0.7 1.3 0 .0 -5 .0 1.1 1.1 0.9 0 .1 -3 .4 1.3 0.9 1 .6 0 .0 -6 .4 Cholesterol 215 218 37 140-293 244 231 43 191-331 219 223 39 157-277 225 231 33 178-277 HDL 55 54 11 40-78 61 58 27 31-121 53 49 1 0 4 0 - 7 7 54 57 18 3 1 -1 0 0 Triglycerides 94 78 39 4 5 -1 7 7 159 118 129 36-463 1 2 0 99 61 49 - 254 117 95 72 37-262 Aik Phos 59 59 17 3 0 -9 1 62 63 11 4 3 -8 0 61 61 18 3 0 -9 4 57 56 1 2 39-77 GGT AST 20 18 14 8-65 32 2 1 26 24 2 2 7 1 5 -3 7 25 23 8 13-111 26 16 2 1 7-80 1 5 -4 4 25 2 2 7 14-38 25 24 16 26 23 8 6-107 16-49 ALT 24 2 1 1 0 12-41 27 25 14 10-61 24 2 1 1 1 11-46 24 2 1 11 12-44 Total Bilirubin 1 .2 1 .2 0.3 0 .5 - 1.9 1 .2 1 .2 0.4 0 .8 - 2 . 0 0.9 0.9 0.3 0 .5 -1 .7 1.1 1 .0 0.3 0 .7 -1 .9 Direct Bilirubin 0 .1 0 . 1 0.04 0 . 1 - 0 . 2 0 .1 0 .1 0.04 0 ,1 - 0 ,2 0 .1 0 .1 0 .1 0.0-0.3 0 .1 0 . 1 0.03 0 . 1 - 0 . 2 BUN 18 18 4 1 5 -2 7 2 2 19 15 14-71 18 18 4 1 3 -2 5 19 19 3 1 4 -2 4 Creatinine 1 .2 1 .2 0 . 2 1 .0 - 1.7 1.5 . 1.1 1.3 0.9-5.8 1.2 1 .2 0 .2 0.8-1.5 1 .1 1.1 0 . 2 0 .8 - 1 . 6 Glucose 84 8 6 14 6 0 - 104 8 8 92 15 5 0 - 107 87 95 2 0 4 8 -1 1 4 91 90 14 68-1 1 5 1 Mean is significantly different (P < .OS, Bonferroni (Dunn) t test) from the mean of the 1" quartile 1 Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from the mean of the 21"1 quartile -- * atrfomi rp < ns Bonferroni iDunnl t test) from the mean of the 3" 1 quartile  Table 8 Antwerp Male Non-Production Employees (N = 56) Thyroid Results* by Quartile of Serum PEOS Distribution** 3M Company Page 37 o f 121 TSH T4 FreeT4 T3 THBR FTI Ouartile 1 (N = 14) Mean Median SD Range 2 .1 2 .0 l.l 0 .4 -4 .2 8.9 8.9 1 .1 6 . 8 - 10.4 1 . 2 1 . 2 0 . 2 1 . 0 - 1.5 131 128 16 1 0 6 -1 6 4 33 34 2 30-36 2.9 3.0 0.3 2.3 - 3.4 Quartile 2 (N = 13) Mean Median SD Range 2 . 0 1.9 1 . 2 0 . 7 - 5 . 4 7.8 8 . 6 1.5 5 . 0 - 9 .4 1 . 1 1 . 2 0 . 2 0 . 9 - 1.5 1 2 0 118 1 2 103 - 145 35 33 4 3 0 -4 2 2 . 6 2.7 0.4 2 .0 - 3 .4 Quartile 3 (N = 15) Mean Median SD Range 1 . 6 1.7 1 . 0 0 . 0 3 - 4 .3 7.9 7.7 1.3 5 .7 - 9 .8 1 .1 1.1 0 .2 0 .9 -1 .5 128 126 25 91-161 35 34 ,3 2 8 -4 1 2.7 2.7 0.4 2 .1 -3 .5 Quartile 4 (N = 14) Mean Median SD Range 2 . 0 1 . 6 1.4 1 .0 - 6 . 1 7.9 7.7 1.9 4 .2 - 1 1 .4 1 .1 1 . 2 0 . 2 0 . 9 - 1.4 125 129 18 87 - 147 35 34 2 3 2 - 4 1 2.7 2.7 0 . 6 1 .7 - 3 .7 N o significantly different (P < .05, Bonferroni (Dunn) t test) mean values S e e Table 7'for serum PFOS quartile distribution 000169 Table 9 Antwerp Male Production Employee (N = 49) Hematology Results* by Quartile of Serum PFOS Distribution** 3M Company Page 38 of 121 HCT HGB RBC WBC Platelets Quartile 1 (N = 14) Mean Median SD Range 44 44 2 40 - 48 15.1 15.0 1.1 12.2-17.0 5.1 5.1 0 . 2 4.8 - 5.6 6 . 6 6.4 1.3 5 .1 - 1 0 .1 228 226 23 1 8 3 -2 5 8 Quartile 2 (N = 13) Mean Median SD Range 47 47 2 4 2 -4 9 15.6 15.5 0.7 1 4 .3 -1 6 .5 5.1 5.1 0.3 4 .6 - 5 .6 6.9 6.5 1.7 4.7 - 10.7 267 270 49 206-353 Quartile 3 (N = 15) Mean Median SD Range 46 46 3 4 2 -5 1 15.4 15.3 0 . 8 1 4 .0 - 17.0 5.1 5.1 0.3 4 .5 - 5 .7 6.5 6 . 0 2 . 1 3 .8 - 1 1 .0 225 2 2 1 53 1 2 9 -3 3 5 Quartile 4 (N = m __________ Mean Median SD Range 45 45 2 4 1 - 5 0 15.3 15.3 0 . 8 1 4 .1 -1 7 .1 5.0 5.0 0.3 4 .7 - 5 .5 6.5 6.4 1.3 4 . 9 - 9 .6 234 234 39 J72-3 0 6 No significantly different (P < .05, Bonferroni (Dunn) t test) mean values See Table 7 for serum PFOS quartile distribution 000170 PFOS Antwerp Female Production* and Non-Production Employee (N = 49) FJuorochemical, Demographic and Clinical Chemistry Results by Quartile of Serum PFOS Page 39 of 121 Ouartile 1 (N = 12) Mean Median SD Range Ouartile 2 (N = 1 2 ) Mean Median SD Range Ouartile 3 (N = 13) Mean Median SD Range Ouartile 4 (N = 12) Mean Median SD Range 0.06 0.06 0 .0 1 0 .04-0.08 0.09 0.09 0 .0 1 0 .08-0.10 0 .1 1 0 .1 1 0 .0 1 0.10-0.14 0.26'-23 0 .2 1 0.13 0 .1 5 -0 .5 5 PFOA 0.03 0 .0 2 0 .0 2 0 .0 1 -0.08 0.03 0 .0 2 0 .0 1 0 .0 1 -0.06 0.04 0.03 0 .0 1 0.02-0.07 0 .2 0 2 0.09 0.31 0 .0 2 - 1 .1 1 TOP 0.08 0.07 0 . 0 2 0.05-0.12 0.09 0.09 0 .0 1 0.07-0.11 0 .1 2 0 .1 1 0 .0 2 0.09-0.15 0.401,2,3 0.26 0.34 0.13-1.25 Age 32 31 8 24 - 50 36 34 9 24-52 38 36 5 3 1 -4 8 37 36 6 29 - 52 BMI 23.8 23.5 2 .6 18.8-28,3 21.9 2 1 .8 2.5 ;l8.4-26.3 2.3.7 21.3 4.6 17.3-32.3 2 1 .8 2 2 . 0 1.7 18.3-25.0 Years Worked 73 5 7 0 .8 - 2 2 13 1 2 8 4-29 15* 14 6 9-28 13 13 7 5-29 Cigarettes/day 1 0 3 0 - 10 2 06 0 -2 0 20 5 0-15 2 0 4 0-13 Drinks/day 0 .2 3 0 .1 0.3 0 - 1 .0 0 . 6 0.5 0.4 0.1 - 1.3 0 .6 1 0.4 i 0.4 0.0-1.4 0 .6 0.5 0.5 0 . 1 - 1 .6 Cholesterol 205 195 30 155-253 214 224 45 132-274 208 197 39 160 - 302 207 197 32 164 - 271 HDL 62 60 II 4 6 -8 5 71 72 19 46-121 6 8 64 18 4 3 -1 0 4 72 67 16 5 3 -1 0 4 Triglycerides 1 1 1 99 57 4 6 -2 4 8 73 80 27 26-112 98 93 43 4 6 -1 7 2 94 87 44 32-171 Aik Phos 53 54 14 2 2 -7 0 44 48 14 ,25-61 44 45 1 0 2 6 -6 1 42 42 11 20-59 AST 21 2 0 5 14-31 17 17 5 11-27 18 17 6 9-26 17 15 6 12-33 ALT 14 1 2 7 8-35 12 12 2 8-17 15 13 7 6 - 3 4 11 11 3 7 - 1 8 GOT 12 10 8 3-32 11 11 5 2-19 14 1 0 10 7-41 10 10 4 5-23 Total Bilirubin Direct Bilirubin BUN 0 .8 0 .1 I2 3'4 0.7 0 .1 12 0 .2 0 .5 - 1.2 0.07 0 . 0 - 0 . 2 2 9-16 1 . 0 1 .0 0.3 0 .5 -1 .7 0 .1 0 .1 0.09 0.1 -0 .4 15 15 3 11-23 0 .8 0 .8 0 .1 0 .1 18' 19 0.3 0 .3 -1 .3 0.06 0 .0 - 0 . 2 4 9-22 0.7 0.7 0 . 2 0 .3 - 1 .2 -0 . 1 0 . 1 0 . 0 0 . 1 0 . 1 16' 16 3 1 3 -2 3 Creatinine 0.9 0.9 0 . 2 0 .6 - l.l 0.9 0.9 0 . 2 0.7-1.3 1 .0 1 .0 0 .2 0.7-1.4 1 .0 1 .0 0 .1 Glucose 75 76 16 3 8 -9 8 86 Number of Female employees by production calegory by quartile 01 0 2 Q3 0 4 Production Non-Production 10 II 13 2 10 90 1 2 65 -101 89 91 11 65 - 105 88 90 1 Mean is significantly different (P < .05, BonferToni (Dunn) t test) from the mean of the 1" quartile 2 Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from the mean of (he 2" 1 quartile 3 Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from the mean of the 3"1 quartile 4 Mean is significantly different (P < 05, Bonferroni (Dunn) t test) fro m the mean of the 4lhquartile 17 000171 0 .8 - 1 . 2 49-117 Table 11 Antwerp Female Production and Non-Production Employee (N = 49) Thyroid Results* by Quartile of Serum PFOS Distribution** 3M Company Page 40 of J21 TSH T4 FreeT4 T3 THBR FTI Quartile 1 (N = 2)________ Mean Median SD Hange _________ Quartile 2 (N = 12)_________ _________Quartile 3 (N 13)_________ Mean Median SD Range Mean Median SD Range _________ Quartile 4 (N = 12) Mean Median SD Range 2 . 0 1.9 1.4 0 .0 3 - 4 .9 2.4 2.4 1 .0 0 .6 - 4 .1 2 -2 1 .8 1 .8 0.03-6.7 2 . 6 2 . 0 1 . 6 1. 0 - 6 . 5 . 10.7 11.3 2 .2 6.6-13.8 9.7 9.7 1 .8 6 . 9 - 12.3 - 10.5 10.7 3.6 4 .6 - 1 8 .3 1 0 . 0 9.8 2.3 6 .7 -1 3 .3 - 1 .1 1 .1 0 . 1 0 . 8 - l.3> 1 . 1 1 . 2 0 . 1 0 . 9 - 1.3 1.4 1 .1 1 .0 0 .7 -4 .6 1 .0 1 .0 0 .1 0 .9 -1 .2 - 157 164 29 1 0 6 -1 9 1 128 134 2 2 98-163 159 145 6 6 8 1 - 3 4 5 144 135 34 1 0 9 -2 2 8 * 27 27 5 J9-34 31 31 4 2 5 -3 6 31 32 ,7 2 2 -4 6 29 29 4 2 4 - 3 5 . 2 . 8 2.9 0.5 2 .1 - 3 .6 2.9 3.0 0.4 2 .3 - 3 .6 3.2 2.9 1 .6 1 .8-8.4 2 . 8 2.7 0.4 2 .2 - 3 .4 / No significantly different (P < .OS, Bonferroni (Dunn) t test) mean values See Table io for serum PFOS quartile distribution 000172 Table 12 Antwerp Female Production and Non-Production Employee (N = 49) Hematology Results* by Quartile of Serum PFOS Distribution** 3M Company Page 41 of 121 HCT HGB RBC WBC Platelets Quartile 1 (N = 1 2 ) Mean Median SD Range 40 42 4 29-43 13.3 13.6 1.5 9.4 - 14.9 4.6 4.7 0.4 3 . 7 - 5 . 1 7.7 7.4 1.9 4 . 8 - 10.1 261 246 50 1 8 9 -3 7 9 Quartile 2 (N = 1 2 ) Mean Median SD Range 41 41 3 3 7 -4 5 13.5 13.5 0.7 1 2 .5 -1 5 .0 4.5 4.5 0.3 4.1 - 5 .1 6.3 6 . 0 1.7 3 .9 - 9 .3 275 282 49 211-374 Quartile 3 (N = 13) Mean Median SD Range 40 41 2 3 5 - 4 4 13.3 13.3 0 . 8 1 1 .7 - 1 4 .8 4.5 4.5 0 . 2 4 .2 - 5 .0 7.3 7.2 1.4 5 .4 - 9 .5 277 251 6 8 202 - 426 Quartile 4 (N = 1 2 ) Mean Median SD Range 41 41 2 3 8 - 4 6 13.5 13.6 0 . 8 1 2 .5 -1 5 .2 4.5 4.5 0.3 4 .2 -5 .1 6.5 6.3 1.3 4 .4 - 9 .4 269 260 64 181-406 *No significantly different (P < .05, Bonferroni (Dunn) t test) mean values **Sce Table 10 for serum PFOS quartile distribution 000173 Table 13 Decatur Male Production Employee (N = 161) Fluorochemical, Demographic and Clinical Chemistry Results by Quartile of Serum PFOS Distribution 3M Company Page 42 o f 12 J PFOS PFOA TOP Age BMI Quartile 1 (N = 40) Mean Median SD Range 0.552,3,4 0.55 0.16 0.11-0.75 1.243-4 1.24 0.67 0.06-2.72 l.342M 1.34 0.52 0.14-2.52 43 44 9 2 6 -6 3 29.0 28.1 3.7 24.5-37.6 Quartile 2 (N = 40)' Mean Median SD Range l.0 l ,M 0.99 0.18 0.76-1.30 1.824 1.53 1.05 0.35-4.61 2 .2 0 U 4 2.04 0.79 0.89-4.22 42 41 9 26-61 28.4 27.3 5.2 17.2-50.1 Quartile 3 (N = 41) Mean Median SD Range I.741,2,4 1.74 0.28 1.32-2.29 2.42m 2.37 1.16 0.76-7.48 3.431'2,4 3.32 1.06 1.75-6.61 42 43 8 28-57 29.9 29.2 5.0 22.6 - 45.5 Mean 3.22 u > 3 Quartile 4 (N = 40) Median S D Range 3.03 1 .2 2 2.31 - 10.06 3.881-2 ' 3 3.68 1 .8 6 1.52-12.70 5.751-2-3 5.31 1.77 3.00-12.23 41 41 1 0 27 - 60 28.3 28.3 4.0 19.9-39.2 Years Worked 1 2 4 13 2 - 3 8 13 5 1 2 2-34 17 2 2 1 2 2-38 16 14 11 3-38 Cigarettes/day 8 0 13 0 - 4 0 5 0 10 0-30 90 13 0 - 4 0 4 0 9 0-30 Drinks/day 0 .2 0 0.3 0 - 1 0 .1 0 0 .2 0 -1 0 .1 0 0 .2 0 - 1 0 . 1 0 0 . 2 0 .0 - 1 . 0 Cholesterol 214 2 2 0 43 121 -2 9 6 224 219 42 155-308 213 208 44 147-384 216 210 39 160-319 HDL Triglycerides Aik Phos 42 232 76 41 8 2 9 - 5 9 45 44 8 198 139 32 - 633 165 137 1 0 1 73 2 0 4 4 -1 4 2 74 69 2 2 3 3 -7 5 43 42 11 2 9 -7 0 43 32 - 550 202 167 138 4 4 -7 9 2 195 39-160 78 75 2 2 3 9 - 139 75 43 8 2 8 - 6 4 175 128 39-796 71 2 0 44-126 GOT 33 28 2 2 7 - 1 4 4 29 23 17 1 0 -8 7 29 27 13 11-80 34 30 16 10-71 AST ALT 26 25 7 1 6 -4 2 26 25 7 334 31 12 1 2 -6 3 324 28 17 15-51 25 24 7 6 - 103 334 31 1 2 7-39 10-58 29 26 11 4 4 1,2,3 37 23 15-69 12-99 Total Bilirubin 0.7 0.7 0 . 2 0.3 -1 .5 0 .8 0 .8 0 .2 0 .4 - 1.2 0.7 0.7 0 . 2 0 .4 -1 .1 0.7 0.7 0 . 2 0 .4 - 1.3 Direct Bilirubin 0 .1 BUN 15 . -0 . 1 0 . 1 0 0 0 . 2 0 .1 15 5 9 - 3 3 15 0 .1 0 .1 0.0-0.7 15 4 8-30 0 .1 0 .1 .05 0 .0 - 0 . 2 15 14 3 8-23 0 .1 15 0 . 1 0 . 1 0 .0 - 0 . 6 15 5 6 - 2 6 Creatinine i.l .1.1 0 . 2 0 . 7 - 1 .6 1 .1 1.1 0 .2 0.8-1.7 1.4 1 . 0 2 .2 0.8-15.0 1 .0 1.1 0 .2 0 .8 -1 .4 Glucose 97 91 19 7 5 -1 8 4 93 93 1 0 75-113 99 93 39 74 - 381 92 90 1 2 72 - 129 1 Mean is significantly different (P < 05, Bonferroni (Dunn) t test) from the mean of the 1" quartile 2 Mean is significantly different (P < 05, Bonferroni (Dunn) t test) from the mean of the 2,idquartile Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from the mean of the 3" 1 quartile 000174 Table 14 Decatur Male Production Employee (N = 161) Thyroid Results* by Quartile of Serum PFOS Distribution** 3M Company Page 43 of 121 TSH T4 FreeT4 T3 THBR FT! Quartile 1 (N = 40) Mean Median SD Range 4.5 2.4 10.4 0 .5 - 6 5 .3 7.9 8 . 2 1.3 4 .6 - 1 0 .7 1 . 0 1 . 0 0 . 1 0 . 6 - 1.3 1 2 2 118 19 9 6 - 186 31 31 3 24-38 2.4 2.4 0.3 1 .2 -3 .0 Quartile 2 (N = 40) Mean Median SD Range 2.4 1 .8 2.9 0 .2 - 1 8 .8 8.5 8.5 1.5 3 .3 - 1 1 .4 l.l 1.1 0 .2 0 .4 -1 .4 124 1 2 2 19 9 3 -1 9 6 30 30 2 2 6 -3 7 2.5 2.5 0.5 1 .0 - 3 .4 Quartile 3 (N = 41) Mean Median SD Range 2.4 2 . 1 - 1.5 0 .8 - 8 . 6 8.5 8 . 2 1.7 4 .7 - 1 2 .9 1.1 1 .1 0 .2 0 .7 -1 .5 127 119 24 87 - 1 7 2 31 31 ,3 2 6 -3 7 2 . 6 2.5 0.5 1 .5 -4 .1 Quartile 4 (N = 40) Mean Median SD Range 3.0 2.4 3.4 0 .8 -2 1 .5 8.5 8.4 1 .2 5 .1 - 1 1 .4 1.1 1 .0 0 .1 0 .8 -1 .3 135 136 23 9 7 - 1 9 0 30 30 3 2 5 -3 8 2.5 2.4 . 0.4 1 .9 -3 .4 N o significantly different (P < .05, Bonferroni (Dunn) t test) mean values S ee Table 3 for serum PFOS quartile distribution 000175 Table 15 Decatur Male Production Employee (N = 161) Hematology Results* by Quartile of Serum PFOS Distribution** 3M Company Page 44 of 121 HCT HGB RBC WBC Platelets Quartile 1 (N = 40) Mean Median SD Range 45 45 2.7 39-51 15.2 15.3 0.9 1 3 .3 - 17.2 4.9 5.0 0.3 4 .0 - 5 .5 6 .1 206 6 .0 200 1.3 4 .3 - 1 0 .2 45 12 6 -3 3 2 Quartile 2 (N = 40) Mean Median SD Range 45 45 2 . 2 40-50 15.1 15.2 0 . 8 1 3 .4 -1 7 .3 5.0 5.0 0.3 4 .1 - 5 .6 i 6 . 2 5.9 1 . 6 3.3 - 10.2 224 2 2 2 42 146-353 Quartile 3 (N = 41) Mean Median SD Range 45 45 2.9 38-52 15.2 15.1 1 . 0 12.1 - 17.5 5.2 5.0 1 .8 4.1 - 16.0 6.4 5.9 1 .8 4 .1 - 1 1 .6 223 2 2 0 47 1 2 2 -3 2 8 Quartile 4 (N = 40) Mean Median SD Range 45 45 2.4 39-50 15.2 15.1 0 . 8 1 2 .9 -1 6 .6 5.0 5.0 . 0.4 3 .8 - 5 .9 6.5 6.3 1 .8 3 .8 - 1 3 .5 216 213 46 132 - 307 *No significantly different (P < .05, Bonferroni (Dunn) t test) mean values **See Table 13 for serum PFOS quartile distribution 000176 Table 16 Decatur Male Production Employee (N = 161) Urinalysis Results by Quartile of Serum PFOS Distribution* 3M Company Page 45 of 121 Albumin Blood Sugar Quartile 1 N(%) 1(3) 3(8) 3(8) Quartile 2 N (%) 2(6) 4(10) 1(3) Quartile 3 N (%) 1(3) 4(10) 2 (1.2) Quartile -4 N (%) 1(3) 1(3) 0(0) Number of Employees: Q1 = 40; Q2 = 40; Q3 = 41; Q4 = 40 *See Table 13 for serum PFOS quartile distribution 000177 Table 17 3M Company Page 46 of 121 PFOS Decatur Male Non-Production Employee (N = 54) Clinical Chemistry Results by Quartile of Serum PFOS Distribution Quartile 1(N 13)________ Mean Median SD Range O.I9m 0 . 2 0 0.08 0 .06-0.29 _________Quaililc 2 (N = 14)________ Mean Median SD Range 0.39* 0.39 0.06 0.32-0.49 ________ Quartile 3 (N14)_________ Mean Median SD Range 0.7 l u * 0.70 0.16 0.50-0.98 _________Quartile 4 (Ns 13) Mean Median SD Range 1.6 6 1W 1.19 0.73 1.00-2.95 PFOA 0.34* 0 .2 1 0.54 0.04-2.10 0.34* 0.30 0.15 0.16-0.61 0.54* 0.48 0.28 0.19-1.25 1.17,A3 1.07 0.60 0.35-2.05 TOP .423* 0.37 0.46 0 .0 8 -1 .9 0 0.64* 0.60 0 .2 1 0 .4 0 - 1.12 :0.98'* 0.96 0.24 0.64-1.39 2 291*2'3 1 .8 8 0.91 1.13-3.74 Age 42 44 1 0 2 7 -5 9 42 36 13 28-60 48 51 8 30-56 49 51 6 3 5 - 5 6 BMI 29.5 27.4 6 .0 22.7-40.8 26.3 25.5 4.0 21.7-35.4 29.1 28.7 3.4 25.5-37.3 28.7 29.4 2.3 2 4 -3 2 Yean Worked 15.1 18.7 11.9 0 .8 -3 7 .9 19.6 17.3 13.8 `2.2 -3 8 .5 24.3 28.6 1 1 . 6 2 .3 -3 4 .2 27.8* 31.8 8 . 6 4 .5 -3 5 .4 Cigaiettes/day 5 0 13 0 - 4 0 5 0 11 0 -4 0 20 8 0 -3 0 8 0 15 0 - 4 0 D rin ksJdty 0 .2 0 0.3 0 - 0 . 8 0.3 0 0.7 0 - 2 . 0 0 .2 0 .5 0 - 1 . 6 0 .1 -0 0 . 2 0 0 . 8 Cholesterol 207 199 45 158-305 204 192 42 153-278 203 197 48 144-281 222 233 42 159 - 297 HDL 46 40 14 3 2 -8 2 49 46 14 35-80 43 40 8 34-59 43 42 1 2 24-73 Triglycerides 157 185 63 38 - 254 129 96 64 59 - 241 161 154 65 62-284 232 1 2 2 173 69-5 1 2 Aik Phoi 59 61 15 2 6 -7 9 62 62 17 ` 3 9 -9 8 72 72 15 4 8 -1 0 5 75 73 15 5 2 -1 0 4 GOT 22 AST 25 ALT 28 Total Bilirubin 0 . 8 Direct Bilirubin 0 .1 BUN 14 Creatinine 1 .0 21 8 11-35 2 2 7 16-42 23 16 1 5 -7 4 0 . 8 0 . 2 0.5 - 1 . 0 0 .1 0.07 0 .0 - 0 . 2 13 3 8 - 2 2 1.0 0.1 0 .9 - 1.2 36 25 29 13-119 28 27 1 0 16-48 33 32 2 0 14-91 0 .8 0 .8 0 .2 0 .5 - 1 .0 0 .1 0 .1 0.03 0 .1 - 0 .2 14 14 3 10-18 1 . 0 l.l 0 . 1 0 .8 - 1 .1 29 29 8 15-41 27 25 6 16-39 35 33 1 2 2 4 - 6 6 0 . 8 0.7 0.3 0 .4 -1 .4 0 .1 0 .1 0.06 0 .0 - 0 . 2 15 15 5 8-24 1.1 1.1 0 .2 0.7-1.4 29 22 28 0 .8 0 .1 16 1.1 23 2 2 9-89 23 5 1 4 -2 9 27 6 2 0 -4 1 0 . 8 0 . 2 0 . 4 - 1.1 0 .1 0.07 0 .1 -0 .3 14 4 1 2 - 2 2 1.1 0 .1 1.0-1.3 Glucose 88 89 8 7 6 -9 9 9 89 6 *79-100 94 92 10 70-112 103 91 26 83 166 -- " rP < 05. Bonferroui (Dunn) t test) from tile mean of the 1" quartile -L---------- <*><'"` tiuartile 000178 Table 18 Decatur Male Non-Production Employee (N = 54) Thyroid Results by Quartile of Serum PFOS Distribution** 3M Company Page 47 o f 121 TSH T4 FreeT4 T3 THBR FT! Quartile 1 (N = 13) Mean Median SD Range 2 .1 1 .8 1 .0 0 .8 -4 .2 9.1 9.1 1 . 2 6.9 - 10.9 1 .1 1 .1 0 . 1 0 . 1 - 1.3 124 129 17 9 9 - 1 5 0 30 30 2 29-34 2.7 2 . 8 0.4 2 .0 - 3 .4 Quartile 2 (N = 14) Mean Median SD Range 2 . 1 1.9 1.3 0 .0 3 - 5 .2 8 . 2 7.9 1 . 6 6.2 - 10.7 1 . 1 1 .1 0 . 1 0 . 9 - 1.3 1 2 0 1 1 2 23 9 4 -1 8 0 31 31 3 2 5 -3 5 2.4 2 . 6 0.4 1 .8 -3 .2 Quartile 3 (N = 14) Mean Median SD Range 3.0 2 . 0 . 2.7 1 .6 - 1 1 . 8 8 .0 8 .2 1 .0 1 .1 1.3 6.3 - 10.2 0 . 1 0 .8 - 1 .2 117 114 23 86-164 31 31 3 2 6 -3 5 2.4 2.5 0.5 1 .7 -3 .1 Quartile 4 (N = 13) Mean Median SD Range 1 . 6 1.5 0.9 0 . 4 - 3 . 6 8.7 8.7 1 .2 7 . 0 - 1 0 .9 1 .2 1 .2 0 .1 0 .9 -1 .4 118 1 2 1 13 91 - 1 3 6 30 31 3 2 5 - 3 6 2 . 6 2.5 0.4 2 .0 - 3 .2 N o significantly different (P < .05, Bonferroni (Dunn) t test) mean values **See Table 17 for serum PFOS quartile distribution 000179 Table 19 Decatur Male Non-Production Employee (N = 54) Hematology Results* by Quartile of Serum PFOS Distribution** 3M Company Page 48 o f 121 Quartile 1 (N = 13) Mean Median SD Range Quartile 2 (N = 14) Mean Median SD Range HCT 45 45 3 38-51 45 45 3 4 1 -5 3 HOB 15.2 15.4 1 .2 1 2 .0 - 16.9 15.4 15.0 I.I 1 4 .2 - 17.8 RBC 5.0 5.0 0.3 4 7 - 5 . 5 5.6 4.9 2 . 8 4 .5 -1 5 .1 WBC 6 .1 5.7 2 . 2 4 .1 -1 3 .1 6 .0 6 .1 1 .6 3 .0 -8 .2 Platelets 245 223 62 1 3 4 -3 3 7 219 217 30 172-266 Quartile 3 (N = 14) Mean Median SD Range 44 45 3 4 1 - 4 9 14.9 15.0 0 . 8 1 3 .6 -1 6 .7 4.8 4.8 0.3 4 .3 - 5 .3 6 . 0 5.7 1 .1 4 . 4 - 8 . 6 230 206 58 1 4 9-361 Quartile 4 (N = 13) Mean Median SD Range 45 45 1 4 3 - 4 9 15.0 15.1 0.5 1 4 .0 - 16.0 5.1 5.1 0.3 4 .6 - 5 .5 6.4 6 . 0 1 .6 4 .4 - 9 .8 2 1 2 203 34 167 - 258 No significantly different (P < .05, Donferroni (Dunn) t test) mean values See Table 17 for serum PFOS quartile distribution 0C0150 Table 20 Decatur Male Non-Production Employee (N = 54) Urinalysis Results by Quartile of Serum PFOS Distribution* 3M Compai Page 49 of i: Albumin Blood Sugar Quartile 1 N (%) 0(0) 2 (15) 0(0) Quartile 2 N (%) 0(0) 0(0) 0(0) Quartile 3 N (%) 0(0) 2(15) 0(0) Quartile 4 N (%) 1(8) 0(0) 0(0) Number of Employees: Q1 = 13; Q2 =14; Q3 = 14; Q4 = 13 *See Table 17 for serum PFOS quartile distribution o o o isi Table 21 Decatur Female Production and Non-Production Employee (N = 48) Clinical Chemistry Results by Quartile of Serum PFOS Distribution 3M Company Page 50 o f 12 J PFOS Mean 0 .2 0 3,4 Quartile I (N - 1 2 ) _____ Median SI) Uange 0 . 2 0 0.08 0.06-0.31 __________Quartile 2 (N = 12)__________ ____________ Quartile 3 (N = 12)__________ Mean Median SI) Uange Mean Median SD Range 0.493'4 0.50 0.13 0.32-0.70 0.99l 2 '4 0.92 0.16 0.77-1.30 PFOA 0.4034 0.28 0.47 0.08-1.81 0.783,4 0.60 0.92 0.10-3.50 1.771-2 1.28 1.17 0.25-4.00 TOF 0.483-4 0.34 0.38 0 .2 1 - 1.60 I.024 0.94 0.72 0.33-3.02 2.I41'4 1.83 0 .8 8 0.86-3.54 Age 36 36 8 25 - 47 43 43 11 2 6 -5 8 44 43 6 3 2 -5 0 BMI 27.5 27.4 6 .8 21.5-45.3 25.9 25.5 5.4 20.0-39.3 27.5 28.2 4.5 20.3-33.6 Years Worked II 7 10 2-27 14 13 II 2-27 12 6 10 4-32 Cigarettes/day 2 0 5 0-15 3 0 9 0-30 40 9 0 -3 0 Drinks/day 0 .0 0 0 .1 0.0-0.3 0 .1 0 .0 0 .2 0 .0 - 1 . 0 0 .0 0 0 . 1 0 .0 - 0 . 1 Cholesterol 184 170 40 138-266 2 0 2 2 1 0 31 139-262 206 2 0 0 43 161-313 HDL 55 56 11 33 - 69 60 58 1 2 40-81 6 6 6 6 12 50-91 Triglycerides 96 1 0 0 49 2 4 - 198 109 89 58 41-233 186 94 281 42 -1049 Aik Phos 59 61 16 2 7 -8 1 63 58 19 34-91 68 69 2 2 41 - 100 GOT 14 15 6 6 - 2 6 14 13 6 7-30 28 17 27 1 0 -9 7 AST 22 21 8 1 3-43 18 18 5 11-26 21 19 9 7-39 ALT 20 16 13 9 - 5 8 18 17 7 11-36 22 17 1 2 6-47 Total Bilirubin 0 . 6 0 .6 0 .2 0.2-0.9 0 .6 0 .6 0 .2 0.3- 1.0 0 . 6 0.5 0 . 1 0 . 4 - 0 . 8 Direct Bilirubin 0 .1 0 . 1 0 . 1 0 .0 - 0 . 2 0 .1 0 .1 0.05 0 .0 - 0 .1 0 .1 0 .1 0.04 0 .0 - 0 . 1 BUN 1 2 13 4 5 - 2 0 1 2 13 3 8 - 1 7 13 13 4 6 - 2 3 Creatinine 0 .8 0 . 8 0 . 2 0 .6 - 1 .1 0 .8 0 .8 0.1 0 .7 - 1.2 0.9 0.9 0 . 2 0 .6 - 1 .2 Glucose 89 90 15 7 3 -1 2 5 8 6 86 9 72-110 82 85 8 67-90 ___ _______ Quartile 4 (N = 12) Mean Median SD Range 2.041"3 1.80 0.78 1.38-3.62 1.9812 1.54 1.27 0.85-5.41 3.391,2,3 2.76 1.65 1.99-7.81 44 46 7 3 0 -5 2 29.9 27.8 6 .8 21.0-41.5 15 17 1 0 3 - 32 13 5 15 0-40 0 .1 0 .0 0.1 0.0-0.3 209 206 42 129-287 55 55 1 2 36-78 142 113 94 46 - 394 70 70 15 4 4 -9 5 16 13 9 6 - 3 9 18 17 5 1 1 -3 0 17 14 6 1 0 -2 9 0.5 0.5 0 .1 0 .3 -0 .7 0 . 1 0 . 1 0.05 0 .0 - 0 . 1 1 2 13 5 1 - 18 0.9 0 . 8 0 .1 0 .7 -1 .1 92 89 13 78-123 Number of Female employees by production category by quartile ___ Ql______ Q2 Q3_______ Q4 TV 1 Mean 2 Mean 3 Mean 4 Mean is significantly different(P < .05, Bonferroni (Dunn) t test) from the mean of the 1" quartile is significantly different(P < .05, Bonferroni (Dunn) t test) from the mean of the 2"`1 quartile is significantly different(P < .05, Bonferroni (Dunn) l lest) from the mean of the3"1 quartile is significantly different(P < .05, Bonferroni (Dunn) t test) from the mean of the4,hquartile i'0 0 1 S 2 Table 22 Decatur Female Production and Non-Production Employee (N = 48) Thyroid Results* by Quartile of Serum PFOS Distribution** 3M Company Page 5 1 o f 121 TSH T4 Free T4 T3 THBR FTI Quartile 1 (N = 1 2 ) Mean Median SD Range 2 . 0 2 . 0 1.3 0.03 - 4.8 1 0 . 0 0 . 8 2.7 6 .5 -1 5 .1 1 . 0 1 .1 0 . 1 0 . 9 - 1.3 132 126 26 1 0 2 -1 8 8 28 29 3 24-34 2.7 2.7 0 . 6 1 .7 -3 .8 Quartile 2 (N = 1 2 ) Mean Median SD Range 2 . 6 2 . 2 1.3 0.7 - 4.6 9.0 8.9 2 . 0 5 .8 - 1 2 .2 1.1 1 .0 0 .1 0 .9 -1 .3 127 1 2 0 29 86-176 28 28 3 2 3 -3 6 2.5 2.5 0.5 1 .7 -3 .1 Quartile 3 )N = 1 2 ) Mean Median SD Range .2.4 2 . 1 1 .2 1.0 -5 .2 9.2 8.9 1.7 6 .7 - 1 1 .9 1 .0 1 .0 0 .1 0 . 7 - 1.1 126 119 26 91 - 168 26 26 4 2 2 -3 2 2.3 2.4 0.4 1 .6 -2 .7 Quartile 4 (N = 1 2 ) Mean Median SD Range 2 .2 2 .2 0 .6 1 .4 -3 .6 9.1 8.4 2.5 5 .8 - 1 4 .2 . -1 . 0 1 . 0 0 . 1 0 8 1 . 2 127 1 2 2 32 8 6 - 196 28 28 4 1 8 -3 2 2.4 2.4 0.4 1 .8 -3 .0 *No significantly different (P < .05, Bonferroni (Dunn) t test) mean values "`See Table 21 for serum PFOS quartile distribution 000183 Table 23 Decatur Female Production and Non-Production Employee (N = 48) Hematology Results by Quaitile of Serum PFOS Distribution* 3M Company Page 52 o f 121 HCT HGB RBC WBC Platelets Quartile 1 (N = 1 2 ) Mean Median SD Range 38 38 3 31 - 4 3 1 2 .6 12.7 1 .2 9.9 - 14.4 4.3 4.3 0.3 3 .8 -4 .8 6.7 6.3 2 . 0 4 .2 - 1 1 .7 2803 260 6 8 2 1 2 -4 5 0 Quartile 2 (N = 1 2 ) Mean Median SD Range 40 40 2 3 6 -4 3 13.3 13.3 0 . 6 12.3 - 14.5 4.3 4.3 0.3 3 .7 - 4 .8 6 . 6 6.5 1.9 4.3 - 10.4 228 216 42 185-302 Quartile 3 (N = 1 2 ) Mean Median SD Range 39 39 1 3 6 - 4 1 12.9 1 2 . 8 0.5 1 2 .0 - 13.8 4.4 4.3 0.3 3 .9 - 5 .0 5.9 6 . 2 1.7 2.8 - 8.4 209' 206 34 1 4 7 -2 7 2 Quartile 4 (N = 1 2 ) Mean Median SD Range 40 40 4 3 4 -4 9 13.4 13.4 1.4 1 1 .3 -1 6 .2 4.3 4.4 0.4 3 .9 - 5 .0 7.6 7.5 1.9 4.2 - 10.4 258 254 55 159 - 339 *See Table 21 for serum PFOS quartile distribution 1Mean is significantly different (P < .05,Bonfcrroni (Dunn) t lest) from the mean of the 1" quartile 2Mean is significantly different (P < .05,Bonferroni (Dunn) t test) from the mean of the 2I|Jquartile 3Mean is significantly different (P < .05,Bonferroni (Dunn) ttest) from the mean of the 3rdquartile 4Mean is significantly different (P < .05,Bonferroni (Dunn) t test) from the mean of the 41'1quartile 000184 Table 24 Decatur Female Production and Non-Production Employee (N = 48) Urinalysis Results by Quartile of Serum PFOS Distribution* Albumin Blood Sugar Quartile 1 N (%) 0(0) 2(17) 0(0) Quartile 2 N (%) 0(0) 0(0) 0(0) Quartile 3 N (%) 2(17) 3(25) 0(0) Quartile 4 N (%) 0(0) 0(0) 0(0) Number of Employees: Q1 = 12; Q2 = 12; Q3 = 12; Q4 = 12 *See Table 21 for serum PFOS quartile distribution 000185 Table 25 . iv i Page 54 o f 121 Number of Participants (Percent in Parenthesis) Stratified by Antwerp or Decatur Employee Populations Who Had Above Reference Range Values for Hepatic Clinical Chemistry Tests by Quartile of Serum PFOS Distribution Antwerp ______ Alkaline 1`liospltalasc______ _____________ AST_____________ ______________ ALT______________ ______________ OGT_____________ _________ Total Liver Panel*_______ 01 0 2 Q3 0 4 ________ Ql Q2 Q3 Q4________ Ql Q3 Q3 Q4________ Q1 Q2 03 0 4 _________ Q1 Q2 Q3 Q4 Male Production 0(0) 0(0) 0(0) 0(0) 1(3) 0(0) 0(0) 0(0) 1 (3) 0(0) 0(0) 0(0) 1(3) 1(3) 2(5) 4(11) 3(8) 5(13) 4(11) 5(14) Male Non-Production1 0(0) 0(0) 0(0) 0 (0) 0(0) 0(0) 0(0) 1 (7) 0 (0) 1(8) 0(0) 0(0) 1(7) 1(8) 2(13) 1(7) 2(14) 2(15) 3(20) 1 (8) Female Production*123 and Non-Production 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 1 (8) 0(0) 0 (0) Decatur Male Production456 1(3) 2(6) 2(6) Male Non-Production3 0(0) 0(0) 0(0) Female Production4 and Non-Production 0 (0) 0 (0) 0(0) 1(3) 0(0) 0(0) 0(0) 1(3) 0(0) 4(10) 0(0) 2(14) 0(0) 0(0) 1(8) 0(0) 0(0) 0(0) 3(8) 5(13) 3(8) 11 (28) 1 (8) 1(7) 2(14) 0(0) 1(8) 0(0) 0(0) 0(0) 4(10) 0(0) 0(0) 3(8) 2(6) 6(15) 3(21) 0(0) 1(8) 0(0) 2(17) 0(0) 7(18) 1 (8) 1(8) 8(20) 5(36) 0(0) 7(18) 14(35) 2(14) 1 (8) 2(17) 0(0) ` Include Alkaline Phosphate, AST, ALT, GGT, Total and Direct Bilirubin 1 See Table 4 for serum PFOS quartile distribution 2 See Table 7 for serum PFOS quartile distribution 3 See Table 10 for serum PFOS quartile distribution 4 See Table 13 for serum PFOS quartile distribution 5 See Table 17 for serum PFOS quartile distribution 6 See Table 21 for serum PFOS quartile distribution 000186 Table 26 Anlwerp and Decatur Male Production and Non-Production* (N = 421) Fluorochemical, Demographic and Clinical Chemistry Results by Quartile of Serum PFOS Distribution 3M Company Page 55 o f 121 Quartile I (N = 105)_________ ________ Quartile 2 (N = 105)_________ _________ Quartile 3 (N = 106)__________ __________ Quartile 4 (N = 105) Mean Median SI) Range Mean Median SI) Range Mean Median SD Range Mean Median SD Range PFOS 0.272,3,4 0.29 0 .1 1 0.04 - 0.42 0.601,3,4 0.59 0 . 1 2 0.43-0.81 1.I91,2,4 1.17 0.24 0.82-1.68 2.691W 2.46 1.09 1.69-10.06 PFOA 0.542,3,4 0.25 0.77 0.01-4 .0 3 1 .2 1 1,4 0 .8 6 1.19 0.06-7.04 1.45m 1 . 2 0 1 .1 0 0.12-7.48 2.70,A3 2.43 1.63 0.25-12.70 TOP 0.622,3,4 0.43 0.58 0.05-3.03 1.40U4 1.14 0.89 0.38 - 5.69 2 .I2 1,2,4 1 . 8 8 0.87 0.98-6.61 4.411,2,3 4.06 1.72 1.92-12.23 Age 383 36 1 0 2 3 - 6 0 41 40 1 0 21-63 42* 43 9 22-61 40 40 9 2 7 -6 0 BMI 25.8 25.1 4.0 19.2-40.8 26.9 26.3 4.0 19.0-37.3 27.3 26.7 4.5 17.2-50.1 27.2 26.8 4.5 17.8-45.5 Years Worked 1 2 1 11 1 0 1-38 15 11 1 2 2-38 16' 16 ,1 1 1-38 15 15 1 0 2-38 Cigarettes/day 4 0 9 0-40 5 0 10 0-40 60 10 0-40 6 0 (0 0 -4 0 Drinks/day 0.93,4 0.7 1 .0 0 - 5 0 .6 0.3 0.9 0 -4 0.5' 0 .1 0.9 0 -6 0.5' 0 . 0 0.9 0 - 5 Cholesterol 214. 209 41 140-331 214 217 43 121-308 215 216 39 105-303 222 214 44 122-384 HDL 54 53 15 31 - 121 47 45 11 2 9 -8 0 48 46 13 2 4 -1 0 0 48 45 15 2 6 -1 1 9 Triglycerides 1314 104 95 3 2 -5 2 7 155 130 1 0 2 35-633 169 134 123 32-731 1771 155 123 3 9 -7 9 6 Aik Phos 613,4 62 16 26-98 67 6 6 18 30-142 691 67 2 1 3 0 -1 6 0 70' 67 19 2 1 - 126 GGT 24 2 0 16 7 -1 1 1 29 2 2 2 2 7 -1 4 4 26 23 15 6 - 8 9 30 25 17 7-85 AST 25 24 8 1 3 -5 8 25 24 6 1 6 -4 9 24 24 7 7-51 25 24 . 9 13-69 ALT 264 23 13 1 0 -9 1 28 26 II 10-63 28 26 14 6 -1 0 3 33' 29 19 8 - 9 9 Total Bilirubin l.O3,4 0.9 0.3 0 . 5 - 2 . 0 0.9 0 . 8 0.3 0 . 3 - 2 . 0 0 .8 * 0 .8 0.3- 0 .4 - 2 .0 0 .8 1 0.7 0.3 0 . 4 - 2 . 2 Direct Bilirubin 0 .1 0 .1 0 .1 0.0-0.3 0 .1 0.1 0 .1 0.0-0.7 0 .1 0 .1 0 .1 0.0-0.3 0 .1 0 . 1 0 . 1 0 .0 - 0 . 6 BUN 18 17 7 8 -7 1 17 17 4 9-30 17 16 5 8-31 17 16 5 6 - 3 0 Creatinine 1 .2 1 .1 0.5 0 .8 -5 .8 1.1 l.l 0 .2 0.7-1.7 1.3 1 .1 1.4 0.8-15.0 1.1 1.0 0 .2 0.8-1.5 Glucose 87 89 16 31-1 3 1 91 90 17 4i9 - 184 91 91 17 4 5 -1 6 8 91 89 30 40-331 0001S7 Table 26 (continued) 3M Company Page 56 o f i21 *Number o f male employees by location, production category and quartile (percent in parenthesis) ____________________ Quartile I___________ ______________ Quartile 2____________ ____________ Quartile 3____________ Production Non-Production Production Non-Product ion Production Non-Production ____________ Quartile 4 Production Non-Production Antwerp 38 38 38 1 2 38 4 36 2 Decatur 7 22 40 15 51 13 63 4 Total 45 (43) 60(57) 78 (74) 27 (26) 80 (84) 27(16) 09 (94) 6 (6 ) 1 Mean is significantly different (I* < .05, Bonferroni (Dunn) t test) from the mean of the 1" quartile 2 Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from the mean of the 2 W>quartile 3 Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from the mean of the 3rdquartile 4 Mean is significantly different (P < .05, Bonfeironi (Dunn) t test) from the mean of the 4,hquartile 000188 Table 27 Antwerp and Decatur Male Production and Non-Production Employee (N = 421) Thyroid Results by Quartile of Serum PFOS Distribution* 3M Company Page 57 o f l 21 TSH T4 FreeT4 T3 THBR FTI Quartile 1 (N = 105) Mean Median SI) Range 2 . 0 1.9 1 . 2 0.03 - 5.7 8.3 8.5 1.4 5 .0 - 1 1 .5 1 .1 1 .1 0 . 2 0 . 9 - 1.5 1244 123 17 9 4 - 1 6 4 3 3 .4 33 3 26-42 2.7 2.7 0.5 1.7 - 4 . 2 Quartile 2 (N = 105). Mean Median SI) Range 3.1 2 . 0 6 . 6 0.5 - 65.3 8 . 2 8.4 1.4 4 .2 - 1 2 .0 1.1 l.l 0 .1 0 .6 -1 .4 128 127 2 0 86-186 32 33 3 2 4 -4 1 2 . 6 2.5 0.4 1 . 2 - 4 .0 Quartile 3 (N = 106) Mean Median SD Range ; 2 .1 1.7 2 . 0 0 .2 -1 8 .8 8.3 8 . 2 1.5 3.3 - 12.9 l.l 1.1 0 .2 0 .4 - 1 .6 127 126 2 1 91 - 1 9 6 321 32 3 2 5 -4 3 2 .6 2 .6 0.5 1.0 -4 .1 Quartile 4 (N = 105) Mean Median SD Range 2.5 1.9 2 . 8 0 .5 - 2 1 .5 8.4 8 . 2 1.4 4 .7 - 1 1 .4 . -1 . 1 1 . 2 0 . 2 0 8 1 . 6 132* 131 22 87 - 190 32' 32 3 25-41 2 . 6 2 . 6 0.4 1 .6 - 3 .6 *See Table 26 for serum PFOS distribution 1 Mean is signifibontly different (P < .05, Bonferroni (Dunn) t test) from the mean of the 1" quartile 2 Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from the mean of the 21"1 quartile 3 Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from the mean of the 3rdquartile 4Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from the mean of the 4* quartile 0001S9 Table 28 Antweip and Decatur Female Production and Non-Production (N = 97) Fluorochemical, Demographic and Clinical Chemistry Results by Quartile of Serum PFOS Distribution 3M Company Page 58 of 121 Quartile 1 (N = 24)_________ __________ Quartile 2 (N = 24)__________ __________Quartile 3 (N = 25)__________ __________ Quartile 4 (N g 24) Mean Median SD Kanne Mean Median SD Range Mean Median SD Ranee Mean Median SD Range PFOS 0.073,4 0.08 0 . 0 2 0 .04-0.10 0.134 0.13 0.03 0.10-0.19 0.391 0.37 0.15 0 .2 0 -0 .7 0 1.511,2,3 1.34 0.76 0.77-3.62 PFOA .043'4 0 .0 2 0.04 0.01 -0.23 0.074 0.05 0.07 0.02-0.34 : 0.61' 0.36 0.74 0.04-3.50 1 .8 8 ' 1 3 1.39 1 .2 0 0.25-5.41 TOF 0.093,4 0.09 0.04 0.05-0.26 0.173,4 0.14 0.07 0.09-0.35 0.801,2,4 0.59 0.61 0 .21-3.02 2.771,2,3 2 .6 6 1.44 0.86-7.81 Age 344 34 9 2 4 -5 2 374 36 7 2 5 -5 2 39 38 9 25-58 4 4 1,2 45 6 30-52 BMI 2 2 .8 4 23.4 2.7 18.4-28.3 23.94 2 2 .2 4.3 17.3-32.3 25.5 23.6 6 .1 18.3-45.3 28.71,2 27.8 5.7 20.3-41.5 Years Worked 11 Cigarettes/day I4 Drinks/day 0.44 9 8 1-29 0 4 0 -2 0 0.3 0.4 0 - 1 15 14 7 2* 0 5 0.44 0.3 0.4 3-29 0-15 0 -1 12 2 0.3 10 0 0 19 7 0.4 2-27 0 -3 0 0 -2 14 1 2 1 0 gl.2 0 13 3-32 0 -4 0 o'-2 0 0 .1 0 - 1 Cholesterol 207. 203 39 132-274 203 198 39 138-302 200 2 0 0 32 139-271 208 2 0 2 42 129-313 HDL 66 61 16 4 6 - 121 65 64 16 33-104 63 61 15 3 8 -1 0 4 60 58 13 36-91 THgiycerides 93 Aik Phos 504 OGT II4 90 48 2 6 -2 4 8 91 8 8 41 52 16 2 2 -8 1 44M 44 II 1 0 7 2 - 3 2 13 1 0 8 24-172 20-65 5-41 107 91 592 56 14 1 2 53 32 - 233 164 104 206 42-1049 16 3 2 -9 1 691,2 70 18 4 1 -1 0 0 6 7 - 3 0 2 2 ' 14 2 1 6 - 9 7 AST 19 19 5 11-31 18 16 7 9 - 4 3 19 19 5 11-33 19 18 7 7 - 3 9 ALT 13 12 5 8 - 3 5 16 13 II 6-58 16 15 6 7-36 19 16 1 0 6-47 Total Bilirubin 0 .8 3,4 0 . 8 0 . 2 0 .5 - 1 .2 0 .8 J '4 0 .8 0.3 0 .2 - 1.7 0 .6 1,2 0 .6 0 .2 0 .3 -1.0 0.51,2 0.5 0 .1 0 . 3 - 0 . 8 Direct Bilirubin 0 .1 0 .1 0 . 1 0 .0 - 0 .4 0 . 1 0 .1 O.J 0 .0 - 0 . 2 0 .1 0 .1 0 . 1 0 .0 - 0 . 2 0 .1 0 . 1 0.04 0 .0 - 0 . 1 BUN 14 13 3 9 - 2 3 16 16 4 7-22 14 14 4 5-23 13 13 5 1-23 Creatinine 0.9 0.9 0 . 2 0.6- 1.3 1 .0 1.0 0 .2 0.7-1.4 Glucose 802 82 14 3 8 -9 8 93' 92 13 65-125 0.9 0 . 8 0 . 1 0 .7 - 1 .2 85 87 1 2 4 9 -1 1 0 0.9 87 0 . 8 0 . 2 0 .6 - 1 . 2 87 1 2 67 -123 000190 Table :28 (continued) "`Number of female employees by location, production category and quartile (percent iin parenthesis) Quartile i Production Non-Production Quartile 2 Production Non-Produclion Quartile 3 Production Non-Production Antwerp 3 20 2 17 16 Decatur 0 1 14 7 II Total 3(12) 21(88) 3(12) 2 1 (8 8 ) 8 (32), 17 (6 8 ) 1 Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from the mean of the I" quartile l Mean is significantly different (P < .05, Bonferroni (Dunn) I test) from the mean of the 2I|Jquartile 3 Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from the mean of the 3r>1 quartile 4 Mean is significantly different (P < .05, Bonferroni (Dunn) t test) from the mean of the 4lhquartile 3M Company Page 59 o f 121 Quartile 4 Production Non-Produclion 00 22 22 (92) 2 2 (8 ) 000191 Table 29 Antwerp and Decatur Female Production and Non-Production Employee (N = 97) Thyroid Results* by Quartile of Serum PFOS Distribution** 3M Company Page 60 of J2 1 TSH T4 FreeT4 T3 THBR FTI Quartile t_____________ ________________ Quartile 2_____________ _____________ Quartile 3______________ ______________Quartile 4 Mean Median SD Range Mean Median SD Range Mean Median SD Range Mean Median SD Range 2 . 2 2 . 2 1 .2 0.03 - 4.9 2 .2 2 .0 1.5 0.03 - 6.7 , 2.5 2 .1 1.4 0 .7 - 6 .5 2.3 2 . 2 1 . 0 1 .0 - 5 .2 1 0 .2 1 0 .2 2 . 0 6 .6 - 13.8 9.8 9.8 3.1 4 . 6 - 18.3 9.9 9.5 2.3 5 .8 -1 5 .1 9.1 8.7 . 2 .1 5.8 - 1 4 .2 l .l 1 .1 0 . 1 0 . 8 - 1.3 1 .2 l.l 0.7 0 .7 - 4 .6 1.1 1 .1 0 .1 0 .9 -1 .3 1 . 0 1 . 0 0 .1 0.7 - 1 .2 145 147 28 9 8 - 191 147 139 53 81 - 3 4 5 133 129 31 86-228 127 1 2 0 28 8 6 - 196 29 29 4 19-36 31 32 6 2 2 -4 6 28 27 3 2 3 -3 6 27 27 4 1 8 -3 2 2.9 2.9 0.5 2.1 - 3 . 6 3.0 2 . 8 1.3 1 .7 - 8 .4 2.7 2.7 0.5 1 .7 -3 .8 2.4 2.4 0.4 1 .6 -3 .0 *No significantly different (P < .05, Bonferroni (Dunn) t test) mean values **See Table 28 for serum PFOS quartile distribution 000192 Table 30 Number of Participants (Percent in Parenthesis) by Employee Population Which Had Above Reference Range Values for Hepatic Clinical Chemistry Tests by Quartile of Serum PFOS Distribution 3M Company Page 61 of 121 Antwerp . Decatur Male Employee* Production tod' Non-Production Alkaline Phosphatsc______ _____________AST____________ Ql 02 Q3 0 4 01 Q2 0 3 04 0(0) HD 3(3) 2(2) 3(3) MD 1(1) 4(4) _____________ ALT_____________ 01 Q2 Q3 0 4 1 ' _______ GOT____________ Ql Q2 03 0 4 . 4(4) 4(4) 7(7) 13(12) 6(6) 8(8) 6(6) 12(12) ________ Total Livcf Panel* 01 02 03 04 15(14) 17(16) 17(16) 24(23) Female Employees Production and*1 Non-Production 0(0) 0(0) 0(0) 0(0) 0(0) K4) 0(0) 0(0) 0(0) 1(4) 0(0) 0(0) 0(0) 0(0) 0(0) 2(8) 0(0) 2(8) 0(0) 2(8) Include Alkaline Phosphatase, AST, ALT, GOT, Tolal and Direct Bilirubin 1See Table 26 for serum PFOS quartile distribution 2See Table 28 for serum PFOS quartile distribution 000193 Intercept PFOS Production Job (yes/no) Anlwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked R2= .08 Adj R2 = .06 Natural log Table 3 J Multivariable Regression Model of Cholesterol* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 5.072 0.020 -0.010 - 0.025 0.006 0.001 0.0007 0.035 -0.002 SE 0.081 0.009 0.023 0.025 0.002 0.002 0.001 0.012 ' 0.001 p value .0001 .04 .66 .31 .0002 -.62 -.49 .004 .15 3M Company Page 62 of 121 Partial R2 - <.01 <.01 <.01 .04 <.01 <.01 .02 <.01 000194 Intercept PFOA Production Job (yes/no) Antwerp/Decatur Age . BMI Cigarettes/day Drinks/day Years Worked R2 = .08 Adj R2= .06 Natural log Table 32 Multivariable Regression Model of Cholesterol* by PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 5.069 0.015 -0.012 - 0.032 0.007 0.001 0.0006 0.03 -0.002 SE 0.080 0.008 0.024 0.025 0.002 0.002 0.001 0.01 0.001 p value .0001 .05 . .63 .22 .0001 .64 .52 .005 .21 3M Company Page 63 o f 121 Partial R2 - <.01 <.01 <.01 .05 <.01 <.01 .02 <.01 000195 Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked R2 = .08 Adj R2= .06 Natural log Table 33 Multivariable Regression Model of Cholesterol* by PFOS and PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 5.066 0.015 0.009 -0.018 - 0.033 0.007 0.001 0.0007 0.035 -0.002 SE 0.081 0.010 0.008 0.024 0.025 0.002 0.002 0.001 0.012 0.001 p value <.0001 .16 .26 .46 .20 .0001 .62 .50 .004 . .15 3M Company Page 64 o f 121 Partial R - <.01 <.01 <.01 <.01 .05 <.01 <.0i .02 .004 Intercept TOF Production Job (yes/no) Antwerp/Deeatur Age BMI Cigarettes/day Drinks/day Years Worked R2= .08 Adj R2= .07 Natural log Table 34 Multivariable Regression Model of Cholesterol* by TOF and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 5.065 0.015 -0.018 - 0.034 0.007 0.001 0.0006 0.034 -0.002 SE 0.081 0.006 ' 0.024 0.025 0.002 0.002 i 0.001 0.012 t 0.001 p value <.0001 .02 . .45 .18 .0001 .63 .51 .005 .16 3M Company Page 65 o f 12 J Partial R2 - <.01 <.01 <.01 .05, <.01 <.01 .02 <.01 000197 intercept PFOS Production Job (yes/no) Antwerp/Decatur Age. BMI Cigarettes/day Drinks/day Years Worked R2= .33 Adj R2= .32 Natural log Table 35 Multivariable Regression Model of HDL* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 4.313 -0.005 0.009 -0.059 0.002 -0.019 -0.004 0.083 -0.001 SE 0.090 0.011 0.026 0.027 0.002 0.003 0.001 0.014 0.002 p value <.0001 .64 . .73 .03 .37 <.0001 .0004 <.0001 .51 3M Company Page 66 o f 12i Partial R2 .01 <.01 .17 <.01 .07 .01 .06 <.0l 000198 Intercept PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked R2 = .34 Adj R2= .32 Natural log Table 36 Multivariable Regression Model of HDL* by PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program 3M Company Page 67 o f 121 Parameter 4.326 -0.018 0.028 -0.043 0.001 - 0.019 -0.004 0.084 -0.001 _________ S E ____________ p value_______________ Partial R2 0.090 <.0001 - 0.009 .04 .04 0.027 , .30 <.01 0.028 .13 .14 0.002 .50 <.01 0.003 <.0001 .07 0.001 .0004 .01 0.014 <.0001 .06 0.002 .54 <.01 000199 Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked R2= .34 Adj R2= .32 Natural log Table 37 Multivariable Regression Model of HDL* by PFOS and PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 4.324 0.006 -0.020 0.025 -0.043 0.001 -0.019 -0.004 0.084 -0.001 SE 0.090 0.012 0.010 0.271 0.028 0.002 0.003 0.001 0.014 0.002 p value <.0001 .60 , .04 .36 .13 .50 <.0001 .0004 <.0001 .49 3M Company Page 68 o f 121 Partial R2 .01 .03 <.01 .14 <.01 .07 .01 .06 <.01 000200 Intercept TOF Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked AilJII1- ..U Nttliirfll log Table 38 Multivariable Regression Model of HDL* by TOF and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 4.322 - 0.010 0.022 - 0.050 0.001 -0.019 -0.004 0.084 -0.0009 SE 0.090 0.007 0.027 0.028 ; 0.002 0.003 0.001 0.014 0.002 p value <.0001 . .14 . .41 .08 .45 <.0001 .0004 <.0001 -.58 i Page 69 of 121 Partial R2 .03 <.01 .15 <.01 .07 .01 .06 <.01 000201 Intercept PFOS Production Job (yes/no) Antwerp/Decatur Age. BMI Cigarettes/day Drinks/day Years Worked R2= .28 Adj R2= .27 Natural log Table 39 Multivariable Regression Model of Triglycerides* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 2.768 0.066 0.023 0.151 0.013 0.055 0.008 0.033 -0.007 SE 0.224 0.026 0.065 0.068 0.005 0.007 0.003 0.034 0.004 p value <.0001 .01 , .72 .03 .009 <.0001 .002 .33 .07 3M Company Page 70 o f 121 Partial R - .03 <.01 .10 .02 .10 .02 <.01 <.01 000202 Intercept PFOA Production Job (yes/no) Antwerp/Decatur Age. BMI Cigarettes/day Drinks/day Years Worked R2 = .29 Adj R2= .27 Natural log Table 40 Multivariable Regression Model of Triglycerides* by PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 2.742 0.066 -0.004 0.111 0.014 0.055 0.008 0.029 -0.007 : s e 0.224 0.021 0.066 0.070 0.005 0.007 0.003 0.034 0.004 p value <.0001 .002 .95 .12 .005 <.0001 .003 .15 .11 3M Company Page 71 o f 121 Partial R2 .05 <.01 .08 .02 .10 .02 <.01 .005 000203 Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Dritiks/day Years Worked R2 = .29 Adj R2 = .27 Natural log Table 41 Multivariable Regression Model of Triglycerides* by PFOS and PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 2.734 0.037 0.053 - 0.021 0.109 0.014 0.055 0.008 0.030 -0.007 SE 0.224 0.029 0.023 0.067 0.070 0.005 0.007 0.003 0.034 0.004 p value <.0001 .20 , .02 .76 .12 .004 < .0001 .002 .15 .07 3M Company Page 72 of 121 Partial R2 - .03 .02 <.01 .08 .02 .10 .02 <.01 <.01 000204 Intercept TOF Production Job (yes/no) Antwerp/Decatur Age. BMI Cigarettes/day Drinks/day Years Worked R2=s .29 Adj R2= .27 Natural log Table 42 Multivariable Regression Model of Triglycerides* byTOF and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 2.736 0.056 -0.017 0.113 0.014 0.055 0.008 0.030 -0.007 SE 0.223 0.017 0.067 0.070 0.005 0.007 0.003 0.034 0.004 p value <.0001 .0009 .81 .10 .005 <.0001 .002 .37 .07 3M Company Page 73 o f 12 J Partial R2 - .06 <.01 .08 .02 .10 .02 <.0l <.01 000205 Intercept PFOS Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .18 Adj R2 = .16 Natural log Table 43 Multivariable Regression Model of Alkaline Phosphatase* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 3.718 0.013 0.036 0.149 0.0008 -0.004 0.002 - 0.024 - 0.002 0.083 SE 0.362 0.013 0.032 0.034 0.002 0.004 0.001 0.016 0.002 0.024 p value <.0001 .32 , .26 <.0001 .73 .26 .17 .14 .41 .0006 3M Company Page 74 of 121 Partial R2 - .02 <.01 .11 <.01 <.01 <.01 <.01 <.01 .02 000206 Intercept PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2=.18 AiljltVln Natural log ; Table 44 Multivariable Regression Model of Alkaline Phosphatase* by PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 3.746 0.0001 0.047 0.154 0.0006 -0.004 0.002 - 0.024 -0.001 0.086 SE 0.128 0.010 0.032 0.035 0.002 0.004 0.001 0.017 0.002 0.024 p value <.0001 .99 . .15 <.0001 .80 .24 .18 .14. .52 .0004 3M Company Page 75 of 121 Partial R2 .03 <.01 .10 <.01 <.01 <.01 <.01 <.0I .03 000207 Table 45 Multivariable Regression Model of Alkaline Phosphatase* by PFOS and PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* Parameter 3.747 0.015 -0.005 0.040 0.153 0.0007 -0.004 0.002 - 0.024 -0.002 0.085 SE 0.128 0.014 0.012 0.033 0.034 0.002 0.004 0.001 0.017 0.002 0.024 p value <.0001 .28 . .65 .23 <.0001 .78 .25 .17 .15 .42 .0005 R2= .18 Adj R2= .16 Natural log 3M Company Page 76 o f 121 Partial R2 .02 <.01 <.01 .10 <.01 <.01 <.01 <.01 <.01 .02 000208 Intercept TOF Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= . 18 AdJ R2*=.16 Natural log Table 46 Multivariable Regression Model of Alkaline Phosphatase* by TOF and Ollier Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 3.747 0.006 0.037 0.147 0.0008 -0.004 0.002 - 0.024 -0.002 0.084 Aik Phos SE 0.128 0.008 0.033 0.034 0.002 0.004 0.001 0.016 , 0.002 0.024 p value <.0001 , .47 .27 <.0001 .72 .25 .18 .14 .45 .0006 3M Company Page 77 of 121 Partial R2 - .04 <.01 .10 <.01 <.01 <.01 <.01 <.01 .02 000209 Intercept PFOS Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2 = .25 Adj R2= .23 Natural log Table 47 Multivariable Regression Model of GGT* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 1.246 0.028 -0.003 0.255 0.0003 0.006 0.003 0.117 0.002 0.294 SE 0.239 0.024 0.059 0.063 0.004 0.007 0.003 0.031 0.004 0.045 p value <.0001 .24 . .96 <.0001 .95 .36 .28 .0002 .45 <.0001 3M Company Page 78 o f 121 Partial R' .03 <.01 .07 <.01 , .02 .01 .03 <.01 .08 0002110 Intercept PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .25 Aiij i<1- . 2 y *Nlui-al log Table 48 Multivariable Regression Model of GGT* by PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 1.245 0.032 - 0.020 0.235 0.0009 0.006 0.003 0.116 0.003 0.289 SE 0.238 0.019 0.060 0.065 0.004 0.007 0.003 0.031 0.004 0.045 p value <.0001 0.10 . ' .74 .0003 .84 .35 .28 .0002 .40 <.0001 3M Company Page 79 o f 121 Partial R2 .04 <.01 .06 .01 .02 .01 .03 <.01 .08 000211 Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .25 Adj R2 = .23 Natural log Table 49 Multivariable Regression Model of GGT* by PFOS and PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 1.246 0.014 0.028 - 0.026 0.23 0.0009 0.006 0.003 0.116 0.003 0.288 SE 6.239 0.027 0.021 0.062 0.065 0.004 0.007 0.003 0.031 0.004 0.045 p value < .0001 .60 . .20 .67 .0003 .82 .34 .27 .0002 .46 <.0001 3M Company Page 80 o f 121 Partial R2 - .03 .02 <.001 .06 .01 .02 .01 .03 <.01 .08 000212 Intercept TOP Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* It! = ,25 Alljlfr H 'Natural log Table 50 Multivariable Regression Model of GGT* byTOF and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 1.246 0.029 - 0.028 0.235 0.001 0.006 0.003 0.116 0.003 0.288 SE 0.238 . 0.016 0.061 0.064 0.004 0.007 0.003 0.031 0.003 0.045 p value < .0001 .06 . .64 .0003 .82 .33 .28 .0002 .48 <.0001 3M Company Page 81 of 121 Partial R2 .04 <.01 .06 .01 .02 .01 . .03 <.01 .07 000213 Intercept PFOS Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2 = .09 Adj R2= .07 Natural log Table 51 Multivariable Regression Model of AST* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 2.725 0.013 - 0.022 0.114 0.003 0.002 -0.003 0.052 -0.004 0.055 SE 0.133 0.013 0.033 0.035 0.002 0.004 0.001 0.017 0.002 0.025 p value <.0001 .33 , .50 .001 t .28 .53 .04 .002 .05 .03 3M Company Page 82 o f 121 Partial R2 <.01 <.01 .03 <.01 <.01 <.01 .02 .01 .01 000214 Intercept PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .09 Adj R2 - .07 Natural log Table 52 Multivariable Regression Model of AST* by PFOA and Ollier Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 2.725 0.015 - 0.030 0.105 0.003 0.002 -0.003 0.051 -0.004 0.053 SE 0.133 0.011 0.034 0.036 0.002 0.004 0.001 0.017 0.002 0.025 p value <.0001 .17 , .37 .004 .23 J51 .04 .003 .05 .04 3M Company Page 83 o f 121 Partial R2 .01 <.01 .02 <.01 <.01 <01 .02 .01 <.01 000215 Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BM1 Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .09 Adj R2= .07 Natural log Table 53 Multivariable Regression Model of AST* by PFOS and PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter SE . p value 2.725 0.132 <.0001 0.006 0.015 .68 0.013 0.012 .28 - 0.033 0.034 .34 0.104 '' 0.036 .004 0.003 0.002 ` .23 0.002 0.004 .50 - 0.003 0.001 .04 0.052 0.017 .003 -0.004 0.002 .04 0.052 0.025 .04 3M Company Page 84 o f 121 Partial R2 - <.01 <.01 <.01 .02 <.01 <.01 <.01 .02 .01 <.01 000216 Intercept TOF Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .09 Adj R2= .07 Natural log Table 54 Multivariable Regression Model of AST* by TOF and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 2.725 0.011 -0.031 0.106 0.003 0.002 - 0.003 0.052 -0.004 0.053 SE 0.133 0.009 1 0.034 0.036 0.002 0.004 0.001 0.017 0.002 0.025 p value <.0001 .17 . .36 .003 .24 .51 .04 .003 .04 ..04 3M Company Page 85 of 121 Partial R .01 <.01 .02 <.01 <.01 <.01 .02 .01 <.01 000217 Intercept PFOS Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .27 Adj R2= .25 . Natural log Table 55 Multivariable Regression Model of ALT* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 1.744 0.021 0.017 0.172 - 0.002 0.025 - 0.007 -0.006 - 0.004 0.189 SE 0.165 0.018 0.043 0.042 0.003 0.004 0.002 0.024 0.002 0.032 p value <.0001 .25 .69 < .0001 .50 < .0001 .0003 .79 .10 < .0001 3M Company Page 86 o f 121 Partial R2 - .01 <.01 .06 <.01 .13 .01 <.01 <.01 .05 ' 000218 Intercept PFOA Production Job (yes/no) Antweip/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .27 Adj R2 = .25 Natural log Table 56 Multivariable Regression Model of ALT* by PFOA and Ollier Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 1.761 0.005 0.027 0.186 - 0.002 0.024 -0.007 - 0.005 -0.004 0.190 SE 0.165 0.003 0.041 0.041 0.003 0.004 0.002 0.024 0.002 0.032 p value <.0001 .13 . .51 <.0001 .44 <.0001 .0002 .83 .15 <.0001 3M Company Page 87 o f 121 Partial R2 - <.01 <.01 .07 <.01 .12 .01 <.01 <.01 .05 000219 Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .27 Adj R2 = .26 Natural log Table 57 Multivariable Regression Model of ALT* by PFOS and PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 1.757 0.019 0.004 0.013 0.176 -0.002 0.025 -0.007 -0.006 -0.004 0.187 SE 0.165 0.018 0.003 0.043 0.042 0.003 0.004 0.002 0.024 0.002 0.032 p value <.0001 .29 . .15 .76 <.0001 .50 <.0001 .0003 .80 .11 <.0001 3M Company Page 88 o f 121 Partial R2 - .01 <.01 <.01 .06 <.01 .12 <.01 <.01 <.01 .05 000220 Intercept TOF Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .32 Adj R2= .31 "Natural log Table 58 Multivariable Regression Model of ALT* by TOF and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 1.965 0.029 - 0.054 0.296 - 0.003 0.012 -0.007 0.01 -0.002 0.199 SE 0.193 0.013 0.050 0.051 0.004 0.005 0.002 0.025 0.003 0.04 p value <.0001 .02 , .27 <.0001 .38 .02 .0003 .62 .44 <,0001 3M Company Page 89 o f 121 Partial R2 .06 <.01 .15 <.01 .04 .01 <.01 , <.01 .05 000221 Intercept PFOS Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .29 Adj R2 = .27 Natural log Table 59 Multivariable Regression Model of Total Bilirubin* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 0.209 -0.017 -0.068 - 0.262 0.001 . -0.005 -0.008 0.005 0.0002 -0.015 SE 0.J45 0.015 0.036 0.038 0.003 0.004 0.002 0.02 0.002 0.027 p value <.0001 .25 . .06 <.0001 .58 .19 <.0001 .80 .94 .57 3M Company Page 90 of 121 Partial R2 .03 .01 .18 <.01 <.01 .06 <.01 <.01 <.01 000222 Intercept PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2 = .29 Adj R2= .2 Natural log Table 60 Multivariable Regression Model of Total Bilirubin* byPFOA and Other Potential Explanatory Variables for Antweip and Decatpr Male Employee Participants, 2000 Medical Surveillance Program Parameter 0.210 - 0.004 - 0.078 - 0.265 0.002 -0.005 -0.008 0.005 - 0.0002 -0.018 SE 0.145 0.011 0.037 0.039 0.003 0.004 0.002 0.019 0.002 0.027 p value <.0001 .74 , .04 <.0001 .54 .21 <.0001 .80 .91 .52 3M Company Page 91 o f 121 Partial R2 - .05 .01 .17 <.01 <.01 .06 <.01 <.01 <.01 000223 Table 61 Multivariable Regression Model of Total Bilirubin* by PFOS andPFOA and Other Potential Explanatory Variables for Antwerp and Decajur Male Employee Participants, 2000 Medical Surveillance Program Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* Parameter 0.209 -0.018 0.002 - 0.070 -0.264 0.002 -0.005 -0.008 0.005 0.0002 - 0.016 SE 0.144 0.016 0.013 0.037 0.039 . 0.003 0.004 0.002 0.002 0.002 0.027 p value <.0001 .27 , .86 .063 <.0001 .57 .20 <.0001 .81 .95 .56 R2 = .29 Adj R2= .27 Natural log 3M Company Page 92 o f 121 Partial R2 .03 .02 .01 .16 <.01 <.01 .06 <.01 <.01 <.01 000224 Intercept TOP Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2 = .29 Adj R2= .27 Natural log Table 62 Multivariable Regression Model of Total Bilirubin* byTOF and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 0.210 -0.011 - 0.064 - 0.257 0.001 -0.005 - 0.008 0.005 0.00007 -0.014 SE 0.144 0.009 0.037 0.039 0.003 0.004 0.002 0.019 0.002 0.027 p value <.0001 .25 . .09 <.0001 .62 .19 <.0001 .78 .98 .60 3M Company Page 93 of 121 Partial R2 - .06 .01 .16 <.01 <.01 .06 <.01 <.01 <.01 000225 Intercept PFOS Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2 = .07 Adj R2= .05 Natural log Table 63 * Multivariable Regression Model of TSH* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter - 0.539 0.015 0.109 0.184 0.005 - 0.005 -0.005 0.057 -0.008 0.204 SE 0.327 0.033 0.081 0.086 0.006 0.009 0.003 0.042 0.005 0.061 p value .10 .65 . .18 .03 .36 .56 .17 .17 .13 .001 3M Company Page 94 o f 121 Partial R2 - <.01 <.01 .02 <.01 <.01 <.01 <.01 <.01 .02 000226 Intercept PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2 = .07 Adj R2= .05 Natural log Table 64 Multivariable Regression Model of TSH* by PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter - 0.539 0.018 0.100 0.173 0.006 -0.005 -0.005 0.056 -0.008 0.201 SE 0.327 0.027 0.083 0.088 0.006 0.009 0.003 0.042 0.005 0.062 p value .10 .51 . .23 .051 .33 .56 .17 .18 .13 .001 3M Company Page 95 o f 121 Partial R - .02 <.01 <.01 <.01 <.01 <.01 <.01 <.01 .02 000227 Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .07 Adj R2= .05 ` Natural log Table 65 Multivariable Regression Model of TSH* by PFOS and PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter - 0.539 0.007 0.015 0.096 0.173 0.006 - 0.005 -0.005 0.056 -0.008 0.200 SE 0.327 0.036 0.029 0.084 0.089 0.006 0.009 0.003 0.042 0.005 0.062 p value .10 .85 . .61 .25 .05 .33 .57 .17 .18 -.13 .001 3M Company Page 96 of 121 Partial R2 <.01 <.01 <.01 <.01 <.01 <.01 <.01 <.01 <.01 .02 000228 Intercept TOF Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .07 Adj R2= .05 Natural log Table 66 Multivariable Regression Model of TSH* byTOF and Ollier Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter - 0.539 0.015 0.097 .174 0.006 -0.005 -0.005 0.056 -0.008 0.201 SE 0.327 0.021 0.084 0.088 0.006 0.009 ; 0.003 0.042 0.005 0.062 p value .10 .49 . .25 -.05 .33 .57 .17 .18 .12 .001 3M Company Page 97 o f 121 Partial R2 - .02 <.01 .01 <.01 <.01 <.01 <.01 <.01 .02 0Q 0229 Intercept PFOS Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2 = .02 Adj R2= .01 *Natumi log Table 67 Multivariable Regression Model of T4* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 2.263 -0.003 - 0.003 0.011 - 0.003 0.001 0.0009 - 0.024 0.001 -0.018 SE 0.090 0.009 0.022 0.024 0.002 0.003 0.0009 0.012 0.001 0.017 p value <.001 .78 , .91 .64 .08 .66 .32 .04 .35 .29 3M Company Page 98 o f 121 Partial R2 - <.01 <.01 <.01 <.01 <.01 <.01 <.01 <.01 <.01 0C0230 Intercept PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2 = .03 Adj R2= .01 Natural log Table 68 Multivariable Regression Model of T4* by PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 2.263 0.0003 -0.005 0.010 -0.003 0.001 0.001 -0.02 0.001 - 0.019 SE 0.090 ' 0.007 0.023 0.024 0.002 0.003 0.0009 0.01 0.001 0.017 p value <.0001 .97 , .82 .69 .09 .64 .31 .04 .37 .28 .ivl company Page 99 of 121 Partial R2 - <.01 <.01 <.01 <.01 <.01 <.01 <.01 <.01 <.01 000231 Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2 = .03 Adj R2= < .01 *Natural log Table 69 Multivariable Regression Model ofT4* by PFOS and PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 2.263 -0.003 0.001 -0.004 0.010 -0.003 0.001 0.0009 - 0.024 0.001 - 0.018 SE 0.090 0.010 0.008 0.023 0.024 0.002 0.003 0.0009 0.012 0.001 ' 0.017 p value <.0001 .74 , .86 .87 .68 .09 .65 .32 .04 .35 .29 3M Company Page 100 of 121 Partial R2 - <.01 <.01 <.01 <.01 <.01 <.01 <.01 <.01 <.01 <.01 000232 Intercept TOF Production Job (yes/no) Antwerp/Decatur Age BMI Cigareltes/day Drinks/day Years Worked Triglycerides* R2 = .03 Adj R2= < .01 Natural log Table 70 Multivariable Regression Model of T4* by TOF and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 2.263 0.0002 -0.005 0.010 - 0.003 0.001 0.001 - 0.024 0.001 - 0.019 SE 0.090 0.006 0.023 0.024 0.002 0.003 0.0009 i ' 0.012 0.001 0.017 p value <.0001 .97 . .82 .68 .09 .64 .31 .04 .37 .28 3M Company Page 101 o f 121 Partial R2 <.01 <.01 <.01 <.01 <.01 <.01 <.01 <.01 <.01 000233 Intercept PFOS Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettcs/day Drinks/day Years Worked Triglycerides* R2= .06 Adj R2= .04 Natural log Table 71 Multivariable Regression Model of Free T4* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 0.299 -0.004 - 0.030 -0.021 -0.003 -0.003 -0.0009 0.006 0.002 0.003 SE 0.076 0.008 0.019 0.020 0.001 0.002 0.0008 0.010 0.001 0.014 p value <.0001 .63 . .11 .28 .03 .13 .27 .56 .21 .85 3M Company Page 102 o f 121 Partial R2 - <.0J <.01 .03 .01 <.01 <.01 <.01 <.01 <.01 000234 Intercept PFOA Production Job (yes/no) Antwerp/Decatur Age. BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .07 Adj R2= .04 Natural log Table 72 Multivariable Regression Model of Free T4* by PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program JM Company Page 103 o f l 21 Parameter 0.299 -0.006 -0.025 -0.017 -0.003 -0.003 -0.0009 0.006 0.002 0.004 _____ SE ___________ p value_______________ Partial R2 0.076 .0001 - 0.006 .31 .01 0.019 . .19 <.01 0.021 .41 .02 0.001 .02 .01 0.002 .13 <.01 0.0008 .27 <.01 0.010 .53 <.01 0.001 .20 <.01 0.014 .78 <.01 000235 Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .07 Adj R2 = .04 Natural log Table 73 Multivariable Regression Model of Free T4* by PFOS and PFOA and Ollier Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 0.299 -0.0005 -0.006 -0.025 - 0.020 -0.003 -0.003 -0.0009 0.006 0.002 0.004 SE 0.076 0.008 0.007 0.020 0.210 0.001 0.002 0.0008 0.010 0.001 0.014 p value .0001 .96 . .37 .21 .41 .02 .13 .27 .54 .20 .77 3M Company Page 104 of 121 Partial R2 - <.01 <.01 <.01 .02 .01 <.01 .002 <.01 <.01 <.01 000236 Intercept TOF Production Job (yes/no) Antwerp/Decatur Age DMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .06 Adj R2= .04 Natural log Table 74 Multivariable Regression Model of Free T4* by TOF and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 0.299 -0.004 - 0.025 -0.018 - 0.003 -0.003 -0.0009 0.006 0.002 0.004 SE 0.076 0.005 0.020 0.020 0.001 0.002 0.0008 0.010 0.001 0.014 p value .0001 .37 .19 .38 .02 .13 .27 .01 .19 .79 3M Company Page 105 o f 121 Partial R2 .01 <.01 .02 .01 <.01 < .0 i <.01 <.01 <.01 000237 Intercept PFOS Production Job (yes/no) Antwerp/Decatur Age BMI Cigareltes/day Drinks/day Years Worked Triglycerides* R2 = .35 Adj R2= .34 Nhiih'hI Ip}! Table 75 Multivariable Regression Model of THBR* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 3.589 -0.003 -0.006 - 0.090 -0.0005 -0.001 -0.0007 - 0.015 -0.0002 - 0.003 SE 0.041 0.004 0.010 0.011 0.0008 0.001 0.0004 0.005 0.0007 0.008 p value <.0001 .40 , .55 <.0001 .50 .29 .13 .005 .77 .75 Page 106 of 121 Partial R2 .03 <.01 . .30 <.01 <.01 <.01 .01 <.01 <.01 000238 Intercept PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .35 Adj R2= .34 Niituial log Table 76 Multivariable Regression Model of THBR* by PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 3.589 - 0.003 - 0.006 - 0.089 - 0.0005 -0.001 -0.0007 0.015 - 0.0002 -0.002 SE 0.041 0.003 0.010 0.011 0.0008 0.001 , 0.0004 0.005 0.0006 0.008 p value <.0001 .43 .58 <.0001 .48 .29 .13 .004 .71 .76 3M Company Page 107 o f 121 Partial R - .04 <.01 .28 <.01 <.01 <.01 .01 <.01 <.01 000239 Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .35 Adj R2= .34 Natural log Table 77 Multivariable Regression Model ofTHBR* by PFOS andPFOA and Ollier Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 3.589 -0.003 -0.002 -0.005 - 0.088 - 0.0006 - 0.001 - 0.0007 0.015 - 0.0002 -0.002 SE 0.041 0.005 0.004 0.011 0.011 0.0008 0.001 0.0004 0.005 0.0007 0.008 p value <.0001 .58 . .64 .66 <.0001 .47 .28 .13 .004 .78 .79 3M Company Page 108 of 121 Partial R .03 .02 <.01 .28 <.01 <.01 <.01 .01 <.01 <.01 000240 Intercept TOF Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .35 Adj R2= .34 Natural log Table 78 Multivariable Regression Model of THBR* byTOF and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 3.589 - 0.003 -0.004 - 0.088 -0.0006 -0.001 -0.0007 0.015 -0.0002 -0.002 SE 0.041 0.003 0.011 0.011 0.0008 0.001 0.0004 0.005 0.0007 0.008 p value <.0001 .29 , .69 <.0001 .45 .28 .13 .004 .77 .80 3M Company Page 109 o f 121 Partial R2 .05 <.01 .28 <.01 <.01 <.01 .01 <.01 <.01 000241 Intercept PFOS Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked 'lilfily t i l t h ' i r hi AilJ II ' HU Natural log Table 79 Multivariable Regression Model of FTI* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 1.239 -0.006 -0.009 - 0.078 - 0.003 - 0.0001 0.0002 -0.008 0.001 HUM SE 0.085 0.009 0.021 0.022 0.002 0.002 0.0009 0.011 0.001 mild p value <.0001 .45 , .65 .0004 .03 .96 .82 .44 .41 Id Partial R .01 <.01 .07 .02 <.01 <.01 <.01 <.01 Ml 000242 Intercept PFOA Production Job (yes/no) Antwerp/Decatur Age BM1 Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .l0 Adj R2 = .08 Natural log Table 80 Multivariable Regression Model of FTI* by PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 1.239 -0.002 -0.012 - 0.079 -0.003 -0.00007 0.0002 -0.008 0.001 - 0.023 SE 0.085 0.007 0.021 0.023 0.002 0.002 0.0009 0.011 0.001 0.016 p value <.0001 .77 .56 .0006 ' .03 .98 .80 .44 .47 .15 3M Company Page 111 of 121 Partial R - .01 <.01 .07 .02 <.01 <.01 <.01 <.01 <.01 000243 Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .10 Adj R2= .08 Natural log Table 8 1 Multivariable Regression Model of FTI* by PFOS and PFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 1.239 -0.006 0.0002 -0.010 -0.079 - 0.003 - 0.0001 0.0002 - 0.008 0.001 - 0.022 SE 0.085 0.009 0.008 0.022 0.023 0.002 0.002 0.0009 0.011 0.001 0.016 oCo\ p value < .0001 .49 .66 .0007 .03 .96 .82 .44 .41 .17 JM Company Page 112 of 121 Partial R - .01 <.01 <.01 .06 .02 .02 <.01 <.01 .002 .004 000244 Intercept TOF Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .10 Adj R2= .08 'Natural log Table 82 Multivariable Regression Model of FTI* byTOF and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 1.239 -0.003 -0.010 - 0.078 -0.003 - 0.0001 0.0002 -0.008 0.001 - 0.022 SE 0.085 0.006 0.022 0.023 ; 0.002 0.002 0.0009 0.011 0.001 0.016 p value <.0001 .62 .63 .0007 .03 .97 .81 .44 .44 .16 3M Company Page i 13 o f 121 Partial R2 .01 <.01 .06 .02 <.01 <.01 <.01 <.01 <.01 000245 Intercept PFOS Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .12 A .p! =m ^Natural lug Table 83 Multivariable Regression Model of T3* by PFOS and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 4.702 0.015 0.022 - 0.099 -0.002 0.005 0.003 t - 0.027 - 0.0006 0.020 SE ; 0.074 0.007 0.018 0.019 0.001 0.002 0.0008 0.009 0.001 0.014 p value <.0001 .04 . .23 <.0001 .24 .02 .001 .004 .60 .15 3M Company Page 114 of 121 Partial R2 .01 .01 .03 <.01 .02 .02 .02 <.01 <.01 000246 Intercept PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .13 Adj R2= . 11 Natural log Table 84 Multivariable Regression Model of T3* by PFOA and Ollier Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 4.702 0.016 0.015 -0.109 -0.001 0.005 0.003 - 0.028 - 0.0004 0.018 SE 0.073 0.006 0.019 0.020 0.001 0.002 0.0008 0.009 0.001 , 0.014 p value <.0001 .01 , .41 <.0001 .33 .02 .001 .003 .70 .20 3M Company Page 115 of 121 Partial R2 .02 <.01 .03 <.01 .02 ' .02 .02 <01 <.01 000247 Intercept PFOS PFOA Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* Rj = .13 Adj R2= .11 Natural log Table 85 Multivariable Regression Model of T3* by PFOS andPFOA and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 4.703 0.009 0.013 0.012 -0.109 -0.001 0.005 0.003 - 0.028 - 0.0006 0.017 SE 0.073 0.008 0.007 0.019 0.020 0.001 0.002 0.0008 0.009 0.001 0.014 p value <.0001 .29 . .05 .54 <.0001 .35 .01 .001 .003 .59 .23 3M Company Page 116 of 121 Partial! .01 <.01 <.01 .03 <.01 .02 .02 .02 <.01 <.01 000248 Intercept TOF Production Job (yes/no) Antwerp/Decatur Age BMI Cigarettes/day Drinks/day Years Worked Triglycerides* R2= .13 Adj R2= .11 Natural log Table 86 Multivariable Regression Model of T3* byTOF and Other Potential Explanatory Variables for Antwerp and Decatur Male Employee Participants, 2000 Medical Surveillance Program Parameter 4.702 0.014 0.011 -0.109 - 0.001 0.005 0.003 - 0.028 - 0.0007 0.017 SE 0.073 0.005 0.019 0.020 0.001 0.002 0.0007 0.009 0.001 0.014 p value <.0001 .004 . .54 <.0001 .35 .01 .001 .003 .56 .22 3M Company Page 117 o f 121 Partial R2 .02 <.01 .03 <.01 .02 .02 .02 <.01 <.01 000249 3M Compai Paage 118 o f 1' Figure 1v Linear Regression Model of Triglgycerides* by PFOA* for Antwerp: Male Employees, 2 0 0 0 Medical Surveillance Program /.J -] 5.5 " 5. " N * _ m * 5.1 * Sc ~ 9.5 - .1 ~ I; j . j " '/ # , a * ! - " i 7 ~ . -| i i i I i -i ' | ' 1 < 1 1 1 ' -3 - ` - 3 - 1 - 1 9 1 2 3 1 5 ?FM Summary of Fit RSquare 0.029 Source Model Error C Total Term Intercept In PFOA Analysis ofVariance DF Sum of Sauares Mean Sauare 1 1.863 1.863 204 61.193 0.299 205 63.056 F Ratio 6.211 Prob>F 0.014 Parameter Estimates Estimate Std Error tRatio Prob>ltl 4.695 0.042 111.43 <0001 0.073 0.029 2.49 0.014 natural log 000250 3M Companj Page 119 of 121 Figure 2. Linear Regression of Triglycerides* by PFOA* for Decatur Male Employees, 2000 Medical Surveillance Program Summary of Fit RSquare 0.028 Analysis of Variance. Source Model Error C Total DF Sum ofSauares Mean Sauare 1 2.164 2.164 213 73.969 0.347 214 76.133 F Ratio 6.232 Prob>F 0.013 Parameter Estimates Term________ Estimate Std Error t Ratio Prob>ltl Intercept 5.052 0.041 122.27 <.0001 In PFOA 0.098 0.039 2.50 0.013 natural log 000251 3M Compan ~-xage 120 o f 12 Figure 3. Linear Regression of Triglycerides* by PFOA* for Antwerp ancr Dec Female Employees, 2000 Medical Surveillance Program RSquare Summary of Fit 0.078 Source Model Error C Total Term Intercept InPFOA Analysis ofVariance DF Sum of Sauares Mean Sauare 1 2.519 2.519 95 29.877 0.314 96 32.396 F Raticr 8.01(1 Prob>f= 0.0GK Parameter Estimates Estimate Std Error t Ratio Prob>lt| 4.690 0.081 58.14 <.0001 0.091 0.032 2.83 0.006 *natural log 000252 3M Compan Page 121 of 12 Figure 4. Linear Regression of Triglycerides* by PFOA* for Cottage Grove Male Employees, 2000 Medical Surveillance Program RSquare Summary of Fit 0.008 Analysis of Variance Source Model Error C Total DF Sum of Sauares Mean Sauare F Ratio 1 0.452 0.452 1.076 129 54.251 0.421 Prob>F 130 54.704 0.302 Parameter Estimates Term Intercept InPFOA Estimate Std Error t Ratio Prob>ltl 5.022 0.057 88.04 <.0001 0.032 0.031 1.04 0.302 natural log 000253