Document zdqXdok6DeemZpLvjn1qnLeBm

AR226- [047 3PaMgeColmofpa1n2y1 FINAL REPORT Epidemiology, 220-3W-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 StantDate: March 1, 2000 Protocol Number (not applicable) IRB Approval Exempt Expedited X IRB 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,, PhD.' Michele M. Burlew, M.S." JeanM. Burris, RN, MP.H.' Jeffrey H. Mandel, M.D., MPH. Jeffrey H. Mandel, M.D., MP.H.! 1. 3M Medical Department, 220-3W-05, St. Paul, MN 55144-1000 = E on =3 3=2z x O3538 3 00 GEA NO CB! P3uMaCso2omrpiazn]y 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 SO 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 10 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. 000003 P3aMgeCo3m0pfa2n1y Mean serum PFOS levels for Antwerp production and non-production male workers were 1.16 and 0.42 ppm, respectively. Among Decatur production and nonproduction 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 fests: hematoei (percent), hemoglobin (gil, red blood cells (RBC. 1000/mm"), white blood cells (WBC, 1000/ mm") and platelet count (1000/ mm'; and the following clinical chemistry tests: alkaline phosphatase (TU/L), `gamma glutamy transferase (GGT, IU/L), aspartate aminotransferase (AST, IU/L), alanine aminotransferase (ALT, IU/L), total and direct bilirubin (mg/d), blood urea nitrogen (BUN, mg/dl), serum creatinine (mg/dl), blood glucose (mg/dl), cholesterol (mg/d). 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 simlatng hormone (TSH: uIUmD: serum thyroxine (T4 kit 6 P3aMgeCodmofpa1n2y1 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). 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 ats 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 lipidsarecausal. 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, ALTortotal 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 000005 3PaMgeCSoompfa1n2y1 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 employeesdo 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. 000006 INTRODUCTION 3M Company Page bof 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, otal organic fluorine was measured rather than any specific fluorochemical analyte. Serum perfluorooctanesulfonate (PFOS) and perfluorooctancate (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, 19992). 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; Decatu=r 84).A totalof 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 highertotal 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 19982; 19992). Nor were there consistent associations reported between serum PFOS and several hormone tests including testosterone, estradiol and thyroid stimulating hormone. CISHD. Twas vot prev to dev inferences from the few employees who bad sem 6 7 3PaMgeC7oompfa1n2y1 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 foar 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 distributionsof 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 ofthe toxicology and epidemiology of PFOS and PFOA have been reported elsewhere (3M Company 2000; Alexander 2001a; 2001b; Butenhoff etal 2001; Gilliland and Mandel 1993;1996: Haughom and Spydevold 1992; Olsen et al 1998a; 1998b; 1999; 2000; Pasteotarl 1987; Seacat etal2001a;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 purposeof 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 produce hyplipidemia in rodents Pastoor etal 1987: 0 0 08 3PaMgeCoSmopfa1n2y1 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 earlierreport for Antwerp and Decatur employees which only analyzed for PFOS (Olsen et al 19984; 1999), 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 focusof a separate analytical report (Olsen et al 2001) 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 batteryofclinical 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, 20010). 000009 P3aMgeCdoompfa1n2y1 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/di), red blood cells (RBC, 1000/mm), white blood cells (WBC, 1000/ mm') and platelet count (1000/ mm); and the following clinical chemistry tests: alkaline phosphatase (IU/L), gamma glutamy transferase (GGT, TUL), 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/d), blood glucose (mg/dl), cholesterol (mg/dl), high density cholesterol (HDL, mg/dl) and wiglycerides (mg/d). Urinalyses were only assessed for Decatur employees viathe 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 THER. 000010 --- I Pa3gMe CIo0mopfa1n2y1 Fluorochemical Analyses Sera samples were extracted using an fon-pairing extraction procedure (Hansen et al, 2001). The extracts were quantitatively analyzed for PFOS (perfluorooctanesulfonate), PFOA (perfluorooctanoate), PFHS (perfluorohexanesulfonate), PFOSAA (N-cthyl perfluorooctanesulfonamidoacetate), MS70 (N-methyl perfluorooctanesulfonamidocetate), PFOSA (perfluorooctanesulfonateamide) and M56 (perfluorooctanesulfonamidoacetate) using high-pressure liquid chromatographylelectrospray 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 matcix and additional luorochemical 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, 20015) and Decatur (Olsen et al, 2001). For Antwerp, al 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 PEOSAA 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 (DG0 | | Pa3gMe Cloomfpa1n2y1 ppm) for M5S6. For Decatur, all employee serum values for PFOS, PHS, PFOA and MST0 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%); MS70 (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 (sce 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 saified nays. employees were divided ino quarts of their sem PO. ) Pa3gMe C1o2m0pfa1n2y1 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 ofjob (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). 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 serum PFOS and PFOA levels: were significantly younger: had lower mean BMIs: 000013 Pa3gMe C1o3m0pfa1n2y1 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. Inasimilar fashion Decatur employee dataare 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 (4") mean serum PFOS level was 2.61 ppm (range 1.76 - 6.24 ppm) compared to the lowest quartile (1*) 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 wasonly 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 1* and 3 quartiles. 000014 ee Pa3gMe Cdoomfpa1n21y Ina similar fashion for the 56 non-production Antwerp male employees, their clinical chemistry, thyroid hormone and hematology results are presented in Tables 7, and 9, respectively, fortheir quartile distribution of serum PFOS. In this analysis, the highest quartile hadamean serum PFOS level of 0.90 ppm (range 0.49 - 1.76) compared 10a 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 PP (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 3" and 4" quartiles had higher mean BUN values than the 1* 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 231 - 10.06) compared to 0.55 ppm mean serum PFOS level in the lowest quartile. There were no significant mean demographic differences 00005) Pa3gMe CIo5mopfa1n2y1 between the four quartiles and the only clinical chemistry test that was significantly different was ALT (Table 13). The highest quartile hadasignificantly higher mean ALT level (44 IU/ml) compared to the 1* (33 IU/ml), 2 (32 IU/ml) or 3" (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. Towest quartile meanof0.19 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 levelof 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 1* quartile (Table 23); however, the fourth quartile was not significantly lower than the 1 quartile. Urinalysis findings did not differ by quartile (Table 24). Presentedin Table 25 are the number (and percentage) of Antwerp or Decatur employees which had above reference range values for hepatic clinical chemistry tests. 0000/6 a Pa3gMe Clo6mopfa1n2y1 `These findings in Table 25 are stratified by serum PFOS quartile distribution within each of the gender and production/non-production categories. Because cach 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 4" 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 (4%) had a mean serum distribution of 2.69 ppm (range 1.69 -- 10.06 ppm) compared 10 0.27 ppm mean (range 0.04 ~ 0.42 ppm) compared to the lowest (1%) quartile distribution. It is important to note that the number (and percentages) of Antwerp versus Decatur employees in each of these four quartiles differ (sce footnote to `Table 26). In the lowest (1*) quartile, there is a greater percentageofAntwerp 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 000017 --- ee Pa3gMe C1o7mfpa1n2y1 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 1* quartile compared to the 4* 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 Tocation and production patter as was observed with the production and non-production male employees (Tables 26 and 27). Antwerp female employees predominated in the Towest 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 quantile. 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 000018 Pa3gMe C18omopfa1n21y 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 4" quartile compared to 4 to 8 percent in the 1 through 3" quartiles. 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 4" quartile 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 = I; no = 0); Antwerp/Decatur (1 = Antwerp; 0 = Decatur); age, BMI cigarettesperday, 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 POS and PFOA, and total organic fluorine. (TOP). Provided in tables 31 through 34 are the analyses for these fluorochemical comparisons in relation totheireffect 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 0000/9 Staessen? FaMse C1o5mopfa3n1y in toxicological studies at threshold serum doses that were approximately 2 orders of `magnitude higher than those serum PFOS levels observed in these employees.). Likewise, there was a positive association for PFOA and TOF but not the combined effects of PFOS and PFOA, with cholesterol. Again, thisis 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. PFOSor TOF were significantly associated with HDL, but PFOA was 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 000029 Pa3gMe C20o0mfpa1n21y (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) or FTI (Tables 79 - 82). PFOS, PFOA and TOF were positively associated with T3 although contributed `minimally to the variation explained in the model (see partial R?). 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 productionofperfluorooctanyl 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 appearteod be log normally distributed with the highest values for PFOS at 10 ppm. This upper til 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 000021 Pa3gMe C21omopfa1n21y PFOS, PFOA, PFHS, PFOSAA, M570, PFOSA and M56 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 BMiIs 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; 19994). 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 10 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: Pastor et al 1987; Seacat et al 2001a; 20010; Sohlenius et al 1993). On the other hand, there is inconsistent evidence for hypolipidemia 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 cholesterolortriglycerides (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 000022 Pa3gMe C22o0m1pa1n2y1 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 etal, 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 I through 3 for the Antwerp and Decatur male and female employees.) We therefore believe that it i 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; 19992; 2000; Seacat et al 2001a; 2001). 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 000023 Pa3gMe C23omopfa1n2y1 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. Aretrospective 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 20014) 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 episodesofcare regarding cystitis was similar. No differences were 000024 Pa3gMe C2o4mopfa1n2y1 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 his study design include its cross-sectional nature which does not adequately allow for the assessment of temporal changes. However, the large participationof employees in 2000 who may have participated in the 1994/95 andor 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 chemistry- related 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 andDecaturfluorochemical production and `non-production employees do not show substantial changes in serum hepatic enzymes, 000025 Pa3gMe C2o5mopfa1n2y1 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. ACKNOWLDGEMENTS `The investigators acknowledge the contributions of Kimberly Young in the prepartion of this report. 000026 pees ----ES-- em ------------------ REFERENCES Pa3gMe C26o.m0pfa1m21y 3M Company (2000). SIDS Initial assessment repot: Perfluorooctane sulfonic acid and its salts. St. Paul (MN):3M Company, (unpublished report). Alexander BH (20012). Mortality study of workers employed at the 3M Cottage Grove facility. Minneapolis (MN):University of Minnesota, (unpublished report). Alexander BH (2001b). Mortality study of workers employed at the 3M Decatur facilit 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 (unpublished report) after 26 weeks of oral dosing. St. Paul (MN):3M Company, Gilliland FD, Mandel JS (1993). Mortality among employeesof aperfluorooctanoic 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 Sti Technol 35:766-770. Haughom B, Spydevold O (1992). The mechanism underlying the hypolipemic 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, SugTa (1987). Induction of cytochrome P-450 and peroixome proliferation in rat liver by perfluorinated octanesulfonic acid. In: Perixosmes in BioanldMoedigcinye. (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. 000027 Pa3gMe C27omopfa1n21y OanldsehnepGaWti,c BaunrdrliispiJdMc,liMnaicnadleclhJeHm,isZtorbyeltesLtsRi(n1f9l99u2o)r.ochSeemriucamlpperrofdluucotrioooncteamnpelosuylefeosn.ate JOEM 41(9):799-806. OMlasnednelGWJ,H (L1o9g9a9n6)P.WF,luSoirmopcshoenmiCcAal,eHxapnosseunreKJa,ssBeusrsrmiesnJtMo,fBDuerclaetwurMcMhe,miSccahlumapnedrftilJm.C, plant employees. St. Paul:3M Company (unpublished report). OhelpsaetnicGeWn,zyBmuersri,scJhoMl,esBtuerrollewanMdMl,ipoMparnodteeilnsJiHn (a2m00m0o)n.iPulmaspmerafclhuoorloeoccytsatnookaitnen and production workers. Drug Chem Toxicol 23(4):603-620. OslesreunmGpeWr,lfBuourroloecwtaMneMs,ulfBounrarties (JBP,FOMSa)ndaenld JpeMrf(l2u0o0r1o2o)c.tAanoaltoneg(itPuFdOinAa)l laenvaellyssiisn orfelation 0 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). JOKl,seMnaGndWe,lSJcHhm(i2c0k0l1eb)r.MNDe,scTriieprteinvseJsMu,mmLaograynofPsWe,rBuumrrfilsuoJrMo,chBeumriclaelw lMevMe,lsLaumnodnbgerg `employee program. participants St. Paul:3M of the year 2000 Antwerp fluorochemical Company (unpublished report). medical surveillance (Ol2s0e0n1)G.W,DesLcorgiapntiPveW,suSmimmaprsyonofCsAe,ruBumrrfilsuoJrMo,chBeumrilcaelw lMeMve,lsLaumnodnbgeregmpJlK,oyMeaendel JH participants of the year 2000 Decatur fluorochemical Paul:3M Company (unpublished reporo). medical surveillance program. St Olsen GW, Burlew MM, Hocking BB, Skratt JC, Burris JM, Mandel JH (2001d). An eepmipdleomyieoelso,gi1c99a3n-a1l9y9s8i.sofSet.piPsaouldeMsNo:f3caMreCoofm3paMnDyec(autnuprubclhiesmhiecdarlepaonrtd).film plant PstausdtioeosroTfPa,mLmeoenKiPu,mPeprerriflMuAo,rooGicltlnioeastPeJ-i(n1d9u8c7e)d.heBpiaotchoemmeigcaally aanndd mpoerrpohxoilsoogmiecal proliferation. Exp Mol Pathol 47:98-109. SAS Institute, Inc. (1990). Institute Inc. SAS Users Guide:Statistics Version 6. Cary, NC:SAS S`Seuabc-acthrAoMni.cTdhieotmafryortdoxiPcJi,tHyaonfspeontaKsJs,iCulmepmeerfnluLoAr,ooCcatsaeneMsuTl,foBnicuatcied inJnLrhat(s2o.00fT1oafx)i.col Sci (submitted 2001a). Seacat AM. Thoford PJ, Hansen KJ, Olsen GW, Case MT, Butenhoff JL. Subchronic toxicity Toxicol studies on perfluorooctanesulfonate Sci (submitted, 2001b). potassium salt in cynomolgus monkeys. 000028 Pa3gMe C28omopfa1n21y SPoehrlfelunoiruosocAtKa,neErsiulkfsosnoincAaMci,d HisoagsptotreonmtCi,ndKuicmelraonfdpeMr,oxDiesPoimearlrefaJttWy (a1c9i9d3)B.-oxidation and other activities Pharmacol Toxicol known to 72:90-93. be affected by peroxisome proliferators in mouse liver. 000029 | e3MaCormpanny Table 1 { Number ofEmployee Paricpants nthe2000AntawndeDecratpur Medica Surveillance Programs Antwerp (82259) ProductMiolne(NNo=n20P6r)oduction _ ProductFieomnale N(oVa=-1P9r)oduction som sean sae Bes a. Mana) Decatur (=263) Female (N=48) Production NonProduction Production __ Non:Production was sss WE sane "Percent in parenthesis 000030 | ; Passo Tab2 Demographics CliealChemie and Thyid Results hepaom DEm_0AempT(ESipsotiDoen w ETo) Amvep(iNaosnrtucbioen en) ros ast Lo ue wo oe on rox Lo i a an os os |r Lat 205 17 a oar on ne o x o PS PB a us 2s ue no 62 ne Vers Word w" w is PB 2 Gipsy ` . 5 . 2 s Dinky we 0 ue a ww 0 . Chose ns as as m ns wm wou ss " ss o ss " hers ne wo I 1 2 0 Akos w " wt w a cor nt n nt a ww ast TM % nt % u x ALT n as 3% 2 a 00003] oo 1 Creatinine 2 " ue 12 12 nu p< OF comparetdoDecatur (test) "Pp <.0001 compared to Decatur (t test) 000032 Table 3 Mean Values for Female Employee Demographics, Clinical Participants' Serum Fluorochemical Chemistries and Thyroid Results Levels, PFOS Antwerp (N = 49) 013 PFOA 007 TOF 017 Age 36 BMI 28 Years Worked 2 Cigarettes/day Drinks/day Cholesterol HDL 2? 0s? 208 68* Triglycerides 94 Alk Phos 4 GGT 2 AST 18 ALT 13 `Total Bilirubin 0.8" Direct Bilirubin ol BUN 16 Creatinine 09 Glucose: 85 TSH 23 T 102 Free T4 1 ke] 148 THBR 30! FTL 29 -- 2 p<.05 compared to Decatur (student t test) pp<<..00011cocmopmapraerdedtotoDeDceactautrur(s(tsutduednetntt tetsets)t) 4p <.0001 compared to Decatur (student t test) Decatur (N = 48) 093 123 176 4 217 13 s 0.1 200 59 133 65 18 2 19 0.6 or 2 08 87 23 93 10 128 23 25 0080033 Pa5gMe C32o0mfpa1n2y1 es ecmra | Pcnbricl, DegAvendryCMaelPCrhcteoyn ERneplhoebey(Q8ui1t5e0ofSraPROSDison aRwePEOamEa soa aI me ten aan owan E wwquotoem ewvS e eer Pana ie toe OY A owow mmeam ommams wmeowww+ mmeww mome mwowe mmemm mow wow a4 ammw | Coin YenWotes #24 350 .1 em2-28 s a" 4 j2e-m3 "4 ano 4 e1-m9 1i" isoe 46 e5-n3 ot www ew mW 4 aw wm we a em mo mw I mow ts -- awaan em um wm om @ eos xs wm wm om wm ow wow ww em a ow on uw ae aw w om e wom moa am mm om ow mmosw aw ww ow won mows wk mm x on mwoew nmw C bMiasme 10 m1om03 wm sets mdowm oa or we esa mwoamsmmsmw mde mee+ aa een pti w1 eoem wwemr ewwaee wmeems oowosam ow wn w mmmar ees um Gee 5 mw wo ww 6 em wu wn aw wn ew | T m RbEE atreShaelettE <I08ifbBernsGmm oonaE e etn s 00003, aes ThyridAnRtweesrpeMabyeQPuarrtoofdSEemurpalcoPyRtO(SiNDi=os15bn0o)tion vr QSuee 105152) Qdune20810:30To Wn Queadi a30Stb3 Tonge Wow was sens 85 8 14 cen 81 81 14 sous Pet 2 wm eis Wu on nie LW 02 066 mw om os owes mo mon mew mm op wow mew x 3 mae Mw 1 mw ww 3 me ma a6 es wan as ds on ma 3 2 ea 1999 fNiosirheifetP< 05, Bokve)e1c r vies Passio We QVeuienst5o0 ) ame 8 82 Wo -n0 WW 02 0s be mm ses x x 2 va 2 a ok 16 000035 -- HematoloAgnytwReerspulMsa*lbeyPQruoadrutcitlieonofESmpeluomyePeR(ONS=Di1s5t0i)butionTM* Mein Qbiudes =SO) Torge Wem QMeudne4S-D30) Forge HT 4 6 3 4-H 4 3 wes HOB 155 Ise 08 M0-D4 ISS ISS 09 B21 REC 52 sa 03 4e-s s1 S20) 44-s5 WBC 70 64 18 42-04 73 20 08 A4-NS Pads 20 9 peu 2s Bo SL W0-m ""LNSoegtTiiaosiefrsacPROS< qu5a,rtBoosfirotniio(Dnoe) 15)msn aes ewQuMietdea =Sb) Tome dw 3 es Ise ISS 08 B6-03 SI S103 4759 76 74 16 S2ME 29 0 Me P5eMCsosmaplaznly ew QMuedem44S-b31) Farge wa 3 ans S313 09 Gaon SO So 03 40-58 72 69 21 4s-ise 2 ws 19.36 Ther FCaosmspelr || Fluorochemical DemograpAhnitcwearnpd CMaileaNoCnhePmriosdutcrtyioRensEultms pbylQo(uNya=e3ro6etf)Sierluem PFOS Disibution To i awe on 5 e om oman ox a am os oom or a an eM om-nw x ow mw TM Me mow wean Yaw 85 wm Cmemay 1 0 5 om busy 1 01 ois om om Saom omen ow ais on eecos ow 0s on omos a @ oo ws me wn we ww 6 em 0 0 0 ow 1 1 mse Woawe a on om ow os uw we WM nn 40 Lu Saom anda on ovals on oy-ew os mum 0S MDs 4 aa 1 om es ale W ow e ow e 5000 on oo ead 0a os omen mY 10 om ossea0r 0 a 1 es MW 30 em ss 9 am 2 0 4 om 13 0 16 sees ws uw ow em Tres 9 Ww een Mma mm nm wm aor mw es ae wom 7 mew nr wom ow wa Twimiebs 1312 0 ass a os mo wm mmm we @ @ new mw 2 nam om on 1 sw mom ow ea 12 02 or oad se ben mo ma es a a ow ww ow ww ew 3 om 1 wm ww om ww 00 0 0 esr sw 9 uw nm wn nm nae mw un wen 3 6% ew ow n+ lew uw nu nw 0 lo 0 aris ov Wom swam wow wm Cone 1312 0 wen as 0 0 ees Gu Mw uw wow wm 5 mm erBr an fom nf 5 le Nhe hr bnma mw 4 mm 22 wm ees ms aw wma wen 0 0 er ois a wu ams 000037 | Tables "ThyrAonitdwReerspulMiaslebyNoQnuaPrriolduocftiSoenrEummpPlRoOySesDi(sNi=ut5i6)on Via Qeudinet vS=D14 Ringe [tn a 20 wee i 8 89 LL Gs-4 Bem 12 12 02 does mm me wel TER ww 2 was m 2 30 03 moa MemMeQguainteSO24213) Tonge 20 9 ese Ts se 1s So-se WU 12 02 09-is mus no wows sm 4 oe@ 26 2 06 20-3 Wein QuMiedtaen34xSD15) Fane a6 17 10 0m 9 17 13 S798 WW 02 09-lS mm 3 dele 3 M3 mea 20 2 04 23s o35 gFTc fserraePE(O<S0q5u,aBtoenfdenraotni(oDnua) es) ean aes. FSageot y Wes QMeuienaStD14) Tum 20 16 14 ea 9 70 19 42-u Li i202 09k ns mw sew 3% Mw 2 nea 2 27 06 13-37 aes aMagSny HemsclogAyrtRyesMiablyPrQouduacrtitoonEfmSpelouyPeReO(S=Di49rbuion* Qruee0114 i Que 20t-1n l Questial Que a0i-10 wr wow 2 ww 0 0 2 ne 6 63 ams 8 2 a WB ow mame me ws 07 wis me 53 03 Mame 3 3 08 dere Wie a sie ee as 1 4-1 es 6 a dems 6s 6 13 49% Mas 3 mB wen wm oe mem ww mes mM om mow tetty lreFS< neBdoinoOn e is 000039 rae10 FuooshenAinctlw,eDrepmFoegmraalpehPirocduncdtiConhriacnld hNoenrPsrodiRcetsiuolnts bypQloyuee(eNo=f9e)rm PFOS comp | To e iom om a om amsm e am om oo am-am ai oi en oawEow W 0x5 a en S an w ars.om mor an em omes-ow Gn om oo em-m ow on om smom 0x em on omen or on om om oman mn om oo oman an on om mes ow ew ou anos waa wow x we wow + wm wows wa ww 6 men Booms ae mews owe we a mem mow 6 mem om me 1 mess ET Commty 1 0 3 ew 2 0 6 em 2 0s ews 2 0 4 ap may 0 01 wo ae ase een 66 eae oes 06 as as orete Com ww wen wm 6 mew mo wm wem wm wm neem we eu ws mm ow wm a wm em m6 6 mew nese ww 9 wa mom on wem ww a wm wn 4 mm ama 5 ww mw 4 ww ma ws ow wa a a on ww wor Wom os wm moms wm wom 6 em ww 6 ww ar Wom em omomoa wn won 1 ew ww a mC Gr mow x smo owm ows aw www a ww a sa mse 0 ww esa le ee eno orm wes 0 0 meen eames 01 01 om ao-es ai or am asec ar a ew enw ol 0 aieor woe Wow a ew moma wm wow 4 em ww 3 na om 0 a 02 eeu 0 mo om 0 te wee ta 0 a oni N Gowam% ewtwag ww swu cwmm nteyfwc[<B5wmeer wtQ hemnmoomeemwsrmrr mrtewc new -- G T ara NS emeth hrS oSI iSImSeR he Ee 3 44 a 000049 . _AntwoerrpFeReesPiribyounasndeNooferudumcPiEoGnSEmDplaoyeae (n= 49) a coop que 101212a TRT apace? T Quuteseis lQS uestia TH a0 1s ia oes a 24 to ea 2 is is meer 26 2 16 tees. [mw ow mesos sn sr a ens ws 07 36 ews wo 8 2 eon ES Bom wm owem mm a we mw 6 mews ww ou oem mm moms mew wn 4 mx wm 1 me mm 4 es man mes aos 39 0 es dase ow te mew mm or moe pont feari<e 5Born onDu nis 00004 J scormp | An`HeemratoFlolgyeRePsruoldsu*cbiyoQnuasrntdiNleoofFSreorductmiPoRnOESmDpilsotiybeuet(iNon=4*5) i oQue ite1 01212 ToJ TS i Qute esie1n TS i PeR ae Wr ems me a 4 3 mw 6 wo: ma wa 2 wa WB Bs Be as sews BS ms 0 mmo msm swims 5s Be of mses ME as 47 oa ds As 45 03 Aes 4s ks 02 ase 4s 4s 03 aes We ww ae am 6 wa wes a mw sens 6 6 1 ses "Wm wm ms Wm oe mem Wm me mew ww a ww tA swasn -- | 00004, Tis Passat FiocchI endmChailCcarayr ,R-- eDl yeQumalofSgeuaPROpSDihibiion Equa e 101mt0 l Que n ln queso lPn U. 3 To awn es ow Gin en am on mem ies an nam ame am um iew mona un we amam ME IS meses a 2% 16 067s SES Se 9m Te ix ap awan eM am an amen Man Me meen 9 sn in mena we 8 ws me a ws wa a os mw a a ow ne wi me mw wews me mm mem me mos meas wm 0 sew ve m4 Bam ns wm am wom om aw ww uw Gust+ 0B em 5 0 mem 3 0 a ew + os om Ce m8 mm mw 8 mem mm 4 Wow Md ew Ww oe 4 + me sw 4 mm 6 oe om mm os 8 5 me ee mm mm Ww we mw mw om wm wm mom wm Cr wm om wm mow ww om ow wm x ww wn A wr ow wom ome wom ow ew ow uw om ws wh ow nw I A Wem ss em sw + emo mw 3 am ow ss ew Comoe 4 uw ee Mw Gwen Ww Gm ese wu mos Gee 9 wb mw nm nm mw wm mw wm ww a nw rr Ere a Slee.kn i ea t a meeetn 02g 000043 | Table 14 PesMaCormpainaty "ThyroidDeRceastuulrtMsablyeQPuraordtuiclteioofnSEemrpulmoyPeFeO(SN=Dis1t6r1i)butions Tei QSeudaen| 4S4D0) ange Wem MQefiuane S20D4240) Wangs TS 4s 24 104 05-63 24 18 29 02-85 79 82 13 46-07 8s 85 0S 23-Me FeeTe 10 10 01 06-13 LI LL 02 044 mo omome Bb sew mm Bo wo TBR ww 3 wuem % 2 wey m 20 24 03 1230 25 2s 0s 10-4 NrSoegTae yT oisrfmsPRO<S0q5u,arBtosterobdat(iDown)1s) ca vibes Wem QMuetea 04S->41) Tage 24 20-45 05-86 8S 82 17 4-9 WW 02 02-5 mu mem ww 3 mm 26 25 05 As-4i Wow QMeudems S(3D=40) Tame 30 24 34 asm 85 84 12 Si-l4 WL 10 01 0813 Bs ne B90 WW 3 mn 25 24 04 19-34 000044 aes HematoloDgeycaRteusrulMsa*lebyPrQoudaurcttiiloenofESmepulmoPyR(NeOS=eD1i6s1t)ibuton* HT HOB [wc WC Paw Vin QMaudaen1 0S4D240) Tange as as 27 ms 2 183 09 BIn2 as so 03 wos 61 60 13 43-02 26 Wa mem Vin QMueisteu2nS20,Tonge as es 22 ws ISI S205 D403 so so 03 wise 62 59 Le 3-l02 Ww Wm Wem We QMuedea34-S4D1) Range 6 4s 20 ws 2 ISI 10 MA-MS s2 so 1s 41-0 64 59 IS Alo WW 0 mem #+5o5iTganbflcent1lfyrdsefusP(O0S5q,uao tedis o(Dnune) l es)meao nves FuSeMCsoimapla2n1y "Mew QMuediatnesvSD40) omg 4 as 24 S2 ISI 08 129-166 so so 04 3s-ss 65 63 18 38-ns me Ww 4 mew Table 16 UrinalysDiescaRteusrulMtaslbeyPQruoadrutcitlieoonfESmeprluomyePeFO(NS =Di1s6t1r)ibution Pa3gMe Caosmfpa1n21y Albumin Blood Sugar Quartile N(%) 1 10) 3) 36) QuNar(t%il)e2 26 400) 13) QuNar(til)e 3 10 400) 202) QuaNr(ti%l)e4 10) 13 00) N*SeeuTabmolfeEbm13plfeooryesreesr:umQP1F=O4S0;quQar2ti=l4e0d;istQr3ib=uti4o1n; Q4 = 40 000046 Table 17 Fa3e0 Cdoimopla3n1y ClinicalCDheecmaitsutrryMaRleesuNlotnbPyrQoudaurcttiiloenoEfmpSleoruymeePR(ONS=D5i4s)ibution e21S) a wQuetnic101S =14 R en Qbueeams a$10 ) Emp Wen eQuied$ a e os as 00 oo 6.0m 0 0% 0m m-0m 07% om ols o%-0s L&T Le on im-2ss or ox om ow ober 0% 0 ois Ol-ds 0S 04 0% ow-in LY In ae 03-2 or aa on ow mio 0M OW 0 iz OW 0% 0M 0G-1 29% im ool Ln-sm a uw ow mew oe ow on ma ws 8 os 8s 6 nw a 3s me 6 mien ws ms 40 wise mw 4 ww m1 me 3 wm Yemwetst 181 WI U9 0M me m3 Ba 2eMs M0 me 6 DoW mE se 4s Cpe 5 0 3 oe 5 0m jee 2 0 4 om 8 0 3 ow sy 02 @ ows wo 01 20 eo as ous a 0 0 oor ed Ww a ews mm a wm ww a ww om ma mem ou " @ wu wm oe wu ww a @ + uw a un un mda 19 WS wes ms 6 sow de is 6 eam om mom em | mma wa us ww @ @ no ww nm om a as mn 15 soo oar 2 ws wes % 3 pas 0 4 ma mm on mC ast 5 om 1 wa mw ow wa m3 6 ww mB 5 ud ar a 0 we ww wm om ow we wx 0 om we mmo ma TwBabe 08 03 02 @s-io 0% 0s 02 0s-is 05 07 03 G44 or op 02 0aew Diabla 41 01 om apex a1 01 0m oi-o2 of G1 om 00-2 01 a1 om e103 a Wom em wo wa mew as ss ex ww 4 na cms 10 10 01 G2 0 Ma ok LW 01 en WW a Weis iw 8B 4 ww B 6 mw wm 0 wm ww x we NNieieeemrnmbdenbntantiytyyffllfnrsn (((7<<<<025055.DDDDenelrerrornnn((((DDeDnre))rs1 ))foooommm ehemimcnooofffhe243{octtllleee 00004 7 ers "TyDrerdcRteaMlitbeyNQounaPrrtiofoSnevEmpPlFoySeDei(si5b6ot)ionsTM Que 01=13 ! TH Mean nm mw esa Median SD__ Range Ww a ees EO mom mp maw mm we 2 mex mw oa ee eee Que ia 1 mw MeanMedian SD 43 Range omesz se 6 own mm on em mw a mas 2 36 0 wer L ptyrrs <5,ritrsvne es cs Quuseanizta Mien Median SD Range 0 2 a tems ww 1 ees mm DK wu 5 ms 1 0s man oMopnars PO Mean Median SD__ ange ds is 0 0436 a @ iz 70-9 wm Bo uw 3 mw 2 2 ok en | 000048 Table 19 HematoDleocgaytuRresMualltsebNyonQuParrotdiulectoifoSneErmupmlPoFyOeeS(DNis=t5i6b)ution** 3PaMgeCsotmlpa1n21y Tei QNuelasi1 vS=D11) Tonge Wain MQautuini2eS84a1)ngo ewn QMuedean304S1D4) Fangs Wem QMuediatne S40D4-12) Tange Her us es 3 wes 4s 4s a wen ws 3 ae ss 1 8-e HaB. 152 154 12 120-169 154 150 1 2-178 149 150 08 136-167 150 ISI 05 140-160 REC 50 So 03 47-55 S649 2 4s-1 45 48 03 43-53 Si S103 46-53 WC 61 $7 22 41-B1 60 61 le 30-82 60 ST LL 44-86 64 60 16 44-98 De Pads Meeme @ eet m e A rWW--m--6--B-- W -- Ne-- W -- Mel--se-- memw -- seere eeree rsrele es N05oaTagea1 foirsrereumtPRPO<Sq05,aBedesinbi(oDnu) 6) mes vas | 000049 Table 20 UrinaDlyesciastuRresMualtlsebNyonQ-uaPrrtoidluecotfioSnerEummplPoFyOeeS (DNis=tr5i4bu)tion* Pa3gMe C49o0mfpa1n2y1 Albumin Blood Quartile 1 N(%) 00 2015) Quartile 2 N(%) 00) 00 Quartile 3 N (%) 00 205) Sugar 000) 00) 00 --_-- N *SecuTam bolfeEb 1m7plfe ooryesr eesr:umQPIF=OS13q;uQar2ti=le14di;stQr3ibu=ti1o4n; Q4 = 13. Quartile 4 N(%) 18) 00) 00) 000050 Table21 SPMuCosmapat2n1y DelcinteuarlFCehmeamliestPyroRduecstuilosn bayndQNuaorntiPleroodfuScetriuonmEPmFpOlSoyDeiest(rNib=ut4io8n) | EEN Que 4-1 Que 221 Quuieaary Quuicsmay MOS MOL om" om om a-oN 0s 00 on 6m-0% mi om 0 om-1% 2 1s on Two ow ax 0moom On ow a om-i mY uw un osama is im oss-sa or ou ou ou e-em aw an nam 1 In om owes Aw 2% wes mem ne EE na PS ma es mses) m9 Mss W0-w3 ms W245 2ne me [| Yeas m1 0 rm ow mow amon 6 ow am ow ms es ne-us nw am Comey 20 5 0s 3 0 9 em 4 0s ee ns us ow Day 0 0 01 0003 ooo @ 0-0 eo 0 or eo-r ar a0 or soa Ove m0 wu Wm 2 ow ms wn me es on mee mw 8 wen ew we ew sme mmo ss on mem wen Ts % We um mms Mma ma mw es ow am wm me mm eeoe ee om aw mms wm dem wes car sr Mose ex 2 ws oma won 6 wows 0 wm wm om ow ow a ww am wns ow ns ew um aT mo wom ew ww 0 we moon ow eo ww 6 wm Tibiae 06 6 02 0200 06 m6 a2 ovo oe 05 oi eeor as as or esa Dibinte 01 G1 01 0002 01 or oes oa-ar a1 ol oa e001 oor ows ae-or mx em 4 sw omom a Wm nom 4 em om ns ew Coie 08 08 a2 Gen ox 0s ol ea ae 00 02 alr a as or ore Ouse mw ws mens % wo mm ww + ow ww on wm anteofel coloresbypodci QL cocaybQquuanleNMecisnchsdtptcelllfiefnnn <<000555.DBBaortskeornonn(((bDovem)e)fommoibteemmmeeohbfbe gootmree PNernibomncion 3so 08a np nt Bll brn oe eo 000) .1 Te DecatouvrrFoedmRaleesrsodubcyiounasntdeNoofnSPnruhiPoEnOSEDplioeosn(4 = 48) masta | ET Qr ue 1-12 r quem Ques TT Quuesct | TR Free T4 Cm mw wo mom om 01 09-13 ow mem 5 mew Loo or 09-13 ow wm wen mw we 10 10 01 07-n1 0 0 01 08-12 mm 2 wes mom 3 Bw om x 4 mm om om 4 wm YE ifo ar r Ou ic)t nlc 000052 Table23 DecaHteumraFteomloaglye RPersoudlusctbiyoQnuaanrdtiNloeno-fPSreorduucmiPonFOESmpDliosyterieb(utNio=n48) WinQMeudaen 1 0S41a2)rge Wim MQeduanieStD 12 Tonge MT w 3 wew s ew2 kes Wo me m7 12 9a-l4 BIB 06 RI-MS RBC 43 43 03 eds 43 43 03 ai-48 WBC e163 20 4-u7 66 6s 19 43-108 Pads W020 @ aso Mm New wom #n c5 nTale2e 1 aonrsyerda et rFnO(S5.q2u0ar35t,ileDa deriooi (nDopr Le)fote he cnss fae 1) gruee "iMiennmfelyaltrcnay0<0 Daonlkerr ((uane) foomhe es fof h34qgale WenQuMeedasvS=D12) Range 1 ea R925 05 OBS 44 43 03 3950 S92 17 28-ks 00 We MW wen P3ueCisnsziaote2ry1: Wem QMeudeans SvD=12) Rum 0 0 4 uw Ba B44 H3-I 43 44 04 39-50 76 75 19 42-104 wm S I9w Table 24 DecaUtruirnaFleymsiasleRePsruoldtuscbtiyoQnuaarntdilNeono-fPSreorduumctPioFnOSEmDpilsotryiebeut(iNon=* 48) Pa3gMe C5o3mopfa1n2y1 Albumin Blood Sugar Quartile 1 N (%) 00) 207) 000) Quartile 2 N (%) 00) 0 00) Quartile 3 N(%) 20am 305) 00 Quartile 4 N(%) 0 00) 0 N*SeeuTam bolfeEb2m1plfeooryesreesr:umQP1F=OS12q;uQar2ti=le1d2i;stQr3ibu=ti1o2n; Q4 = 12 00005k ess se IMCompany | roo ent Core Coy eh Goofolr Poo ition - EEmer rr e a ,r sar rrde on om nm A aE os to as voy 0 am oh on oh TE am n eaen veeo vm veme re en m SernNa ivwn oMinen tvenr i a E I T aona LLLa. E EEL T oens tom imonot iBonn rmoa mria om 000055 | Tube 26 stor Fluarechemia,ADntewmeorgpaapnhdDiescnadtuCrlMaelaePrCodeucrtitonRaendsNtonb-yPrQoudurcltieoonfS(Nu=m42P1R)OS Dion | a PO, Qeuie105 venPOSee en Qeueot0e Me mo om a on ewon os ax oman ow ow on oacom a om im owem Lin on ems LS UB ue one 16% 4 10 1010% 20 ia omaw Te we ew ao owen % mae we iw om owose 4 ew me Le @a om owe 5 ma Wr? an in imam wo 6 0 ne ma mw wear we wy de mem mw 4s mam ma me 8 nas TE oso 0 ome 5 0 wm ew sr o% wd os eee a on oo wm ee as or ees 0 oe 08 ew os Gin We. wa em am a mow ww won mm 4 mem onda Bs i nm am me wm wee we no momen msm wm Wma wr oe wm www @ ow mm 6 ow mom we ew @ ow @ on ns wwe ew wm on wm nw EE wr ow mow mew mm uw we wx ow ew wm on ew TC TE Co we 2 Ws ols wu e wep mw 6 mw wm neem D0 wan wes sas We es a 0 am 000056 mtrot iecemseein -- PM [. = EEE sIMComypany. "Table 26 (continued) a ionI apye dary ee pe) es gee -w N. PM : M - . wwe mE etth Sshoe<3bBree oPDmovttseremeeee mmeeceCoSmer, | 000057 J. 3MSCompaany. Antwerp andrDeoctaursMitle Pbyrooducttieon sfndeNoon PFrodSuctiDonoEmoplnoyee (N= 421) || ael 2 1s 1am Wm ws sens et ue mers Cm ae mop ose WW Mm Gem i et 08 i a 0 es ase mow am mW en wel mm www to Tm es a Saeta um 4 a0 om mow as Bem uM ol mmm sew mm a a S Sa p a5 1p 2 sens Mm en W120 ote nr mn mem a WT We fPFIeo em +5Lrmm ong.urtefnpfrtesie0nsik CCTooett 000058 | ens LIMeCoemparny Fiuoroshemical,ADnetmwoegrrpapahndicDeancdaCtluirnFiecmaallCehePrmoidsuecytiRoensualntdsNboy nQuParrotdiulcetoifonSe(rNa=m9P7R)OS Distribution RE re See Wan ew | ros a a om os-ow ai on om owen 0W 03 ais 0mm IS ix 0% omela or oot om om co-an om ons 0g oman 06 0% 0% 004% mH in 1m exes Tor a ae om aco on ou 0 am-o3 wom oa ono AMY dw La omer a wows wm ww 1 mea wm 9 ms 4s wm ma ne mew omews ne om a mm ws be @ Wess WP mss was | Vamwekt 1 9 8 am usw 1 am nw 5 am wm 0 3m Cows 0 4 ow #0 seus 2 0 1. ew #0 on oe Dy 0 oe oo of @ oe oo 0 04 ea oo ol om ves Www mem mm moe ww ow wom mm a mew Le a wm ee 6 wom 6 6 8 Mem es no % Teds B 4 Bem aw 4 dem 0 9B wm le I a-ow Mma wm mew Ww 0 mes % 6 me @% nu am wr wom os we ww 1 ea moms omen ww 7 ar Bors Eww mon es es 6 a mw 0 en Tbe 08 08 02 0siz os os 0) ear of 06 a ons of 0s 01 oes Deambe 01 01 G1 00-04 a1 01 oi Gz 01 01 G1 00-01 ol oi On 0-0 ow Wom em ww 4 mw ow 4 sm oB ms am Coe 05 00 02 oe Mo lo 01 e-l 00 or a 02 00 or 01 oe Gwe Wm Mw ww wm ob eas 8 om ew wom on om --_--00005y Table28 continued) MCompary | prsespofiat "NumberoffensecQmpulyee.s by ain,prdicionctorQusederqari (pect inens) uae qutes TS TT non 3 2 " ' . o o I ' ' . , n 2 2 Ww Tm wm Sm wee meme aw hiicstnnbst cnylyt ififnnny (((<<<0035,BBBoeonrkkerssDOnueutes)))ffooomehheereecc sie21 ritlcl.e "Menafectr <y0,Baler (un om nf 4 gle | 000060 | Tables Antwerp a"nTdhyDreocisdtuRresFuelmsalebyPrQoudaurcttiileonofaSnedrNuomnPPrFoOdSucDtiisotnrEimbpultoioynee (N =97) FIMCuomepaln2y1 Vi WiQunite01. Range We WehQrueSrh Wan We WeQluwesSb Rage Mon VetqwunnieSsO Ram | TH 22 22 12 ome4s 22 20 Ls 0m- 25 20 14 036s 23 22 10 10-52 TM 2 102 20 ee-n8 98 98 M1 46-3 99 95 23 SEI a1 87 20 S82 Rem UL 00 0nd 12 Wo 07 07.46 LL 4 01 09-13 10 lo a1 07-2 TR ST I I AJRE ER 0 4 p% Wm 6 ma wm ow 3 mw wm 4 wen wm 25 29 0s 21-3 30 28 13 ures 27 27 05 1238 24 24 04 16:30 NSoeseigTnaibfilcean2t8lyfodrisfeerreunmtP(FPO<S0q5u,artBiolnefdeirsotrniibu(tDiuonna) es) msn values 000061 een a 3MCompany Which Had AboveReferenceRaNnugmebearofePfro iHanps (CPeentsiCnhPeamrnesT)esbtybEymQpluoyaelsPogSuleiuonPFOSDison rn ee en naan ree. ASe Marnk Baapslotues 40 10 30 20 0 0 0 Ge e: d om mew me se ne no rire rat 4b 0m ww am 0 6 te ce cm ke om em ow ew iw am wom | Ae et,TAL. Te i Bn sE e ol teR un 8 rR est | 000062 Tabet MuivareinsdhiOcthReegrPseinotnakExlploanfahtory VearisebsyPeOS {or A550e 0ndMDeecar tSMauleEmnpPPrrogiampns, _ parameter os pave eens son oon wor ) pros om oo o Prion Jo Geshe) TM oo P AnweDecar ous os at he ous om wo - oat oo @ Cipretestiny aor oor a Drink ams oon2 ot Yours Worked om ool is a 3M Compaay. || Partial . <n <a <a o pr pr @ <n RpN=oo0r8ge : 000063 Table 32 M{ooriAvrntrederOytRhaeenrgdePDsoteiecontntiarMloMEadxtpeelaoEnfmaCtpohlrooyylVesasrPrsaileisbnytPsO,A S000 Meta Survie rogram r3M aCompoany Parameter SE erent S000 oom . Pron ois ous Producion ob Oech) 002 ona AnverDecauc 002 ons ne oor om ot oor oo Pr" ous oar Drinkstay on oor Yours Worked 00m oon pvalue wor Partial R* . os <a <a 2 <a wot 0 " <a 2 <a 05 a pr Natio R= 08 AdjR*= 06 000054 i Table 33 MalivarsbleaRnedgrOetshseironPtMeondgealloEfxCplhaonlaetsotreyroVlarbiyabPleRsOS and PFOA for Antwe"r2p00a0nMdeDdeiccaatlurSMuravleiellEamncpeloPyreoegrPaamrticipants, Pa3geM Ctoomrpa2n1y Punmeer SE pave Paral Intercept 5066 oos1 <0o01 . - Pros oots 0010 a6 <0 | PFOA 0009 0008 2 <0 | Production Job (esha) -o018 [ 46 <0 Antwerp Decatur -0033 oos 2 <0 Ae 0007 0002 01 0 | BMI 0001 oo @ <on Cigaretesiday 00007 ooo 5 <0 Drinksldsy os oor2 004 o Years Worked -0002 ooo 1s oo A'd=GRI0=8.06 "Natural log 000065 | | Tes {MailAimOteaenRdFDoeeatmMioEsdexEpofmaiCothtoeVinrPriepsbysTO,F ihc umes Pog eJwosm | mere Parameter SE sass oon p value <omt .Partial R* : or oois 000s <n Podion bein) 0018 oon " pr AnverDesaur oom oon n <n re oom oom oon 0 a oon ao @ <r Cameteitny ooms oon 5 <n Dray oom aon os n | Vous Woke oom oon 15 <n Neorg R'=.08 AdjR = 07 000066 || neers #ros PrionJo ese) Averecate a Bt Cipetestny Drininy Yours Worked No* R'=33 AdjR'= 32 Tabs (oMr AomOlevrvyeaarndRPeDgeernecisitonMEMxeopdaeFnlsoofrnyHDeVLP?rbayisnFtOsS, S000Medal Suen bogum Pumeter SE pale an amo <oon 000s oon " ows ons ES "aos oon oo om = "aon aos <n 004 acon wos om oon <oon "oo01 oo st 000067 rMComepany | Paria . a pr 0 <a @ a <a Inert Proa Producion ob esi) AnwerpDecsur TM i Gipsy Drinksday Years Worked RANio=gr34teiog Table 36 Maund OtlherRPeiogteesvnitonEMrxopdaenlistofryHaVDaLrlbiyesPeFOA for Antw3e0rp00sMndiDteceatSuruMrlevEemlplaoPyrnoegecrPaeimricpans, Parameter se pvalue as om <oon 0018 ows o ous oo EF) 006 oo 5 oui oon B 00 ous <omi 000s oon oot 00s 0014 <omi 0001 oo st 000065 raiiCoemparty | Paral RY . TM <or " <0 o a 6 | <a TEpeLiR enka oo Paamer se pvalue oon oom am ooonno -o robin oo on - powa ai wwrn <a" crmany i on a rYoem r o-m woon o-l #0 Ri=34 AR =32 000063 IM Company | Paral RY -on i"o i-" |b Table 38 MuliavnadrOitbhleerRPeogernetsisailoEnxMpoldanealtoofryHVDaLri*abbylesTOF for Antwe2r0p0i0nMdDeedciactauSruMrvaeliellEamncpeloPyreoegrPaamrticipants, P3aM Ccoompainaty _ Parameter SE Inercept am 00% . Tor -0010 0007 Production Job (yesh) oon oon Antwerpecatur -0050 [ Ase 0001 0002 BMI 0019 00 Cigaretesiday -0004 0001 Drinkslday 0084 ool Years Worked -00009 [3 puiloe Panial <.0001 . kg o a <0 08 15 4s <0 <.0001 o 0008 or <0001 0% 58 <0 AR=GR3=3 32 Naural og i 000070 Table 39 MalivaraanbdlOtRheegrrePsostieonntiMalodEexlpolafnaTtrogryceVarriidabsl*ebs yPROS for Antwe2r0p0a0nMeDdeicaaltuSruravleiellEamnpceloPyreoegPaamriipnts, IM Company v ner ee 2768 SB 0224 . pros 0066 0026 Production ob (resin) [3 0065 AmwerpDectur 01st 0068 Age oor 000s i 005 [a puke <o001 o n 9 <o001 Pak - os <on a0 @ 10 Cigareestiay 0008 0003 0 Drinksday 0033 oo EY <or | Years Worked 0007 0004 o <or ARiGeRs= 21 "Naural log 000071 Table d0 M{oirAvratanedrOyReahgnrdesaDseiiconnaitolr MlEaxtpoelafEnTmatprolroiyyVegeahPscaeiesbniytdsP,eFOsA 2000 edie Survelanc Program Parameter i SE pale ere 270 oz <a . Pron ass oa oo Production Job Geshe) 0004 00s ss AnverpDecauc om oom Fs ae oie aos 0s oa ooss oan <oont Cipuetestsy ome oom wo Dinky om oo is Years Worked oan oat a rIMCaompoany | Partial B . os <or 1 <a ws R'=29 AdjR?= 27 Naural log 000072 | Table 41. Multivariable aRengdrOetsshieornPMotoednetilalofETxrpilgalnyacteorryidVeasribayblPeRsOS and PFOA for Antwe2r0p0a0nMdeDdeiccaatuSrurMvaeliellEanmcpeloPyreoegrPaamcpants, Pawmee SE puke Inereept 2m 0224 <0001 . Pros [2 [ 2 PFOA 0053 [3 o Production 1b (yes/no) 00 0087 76 r-- 0109 oom n Age oot 000s 004 M1 o0ss 0007 <.0001 Cigartesday 0008 0003 0 Drnkslday 0050 00s 15 Years Worked 0007 0004 o ARiG=R2I9 =2) "Netwral log 000, 073 PIeMrCroompta2n)y Pari] B o <0 08 o 10 o <0 <0 To Tor Podwion bso) AnmerDecatc we Cimetestny Dinky Yous Worked fh AR'G=R2I9= 27 Ta MfoliAvmdrereoyRtgndreePsoiotsniMoiEdtexofEpTrtilVegaaaiclsby ,TOF Soo edn eile Pog 26 Parameter SE on pvalue <omt 005s oon oo 0007 00s a on oom 0 oon oo0s os ooss oom <omt ooos oom w oon TM = oom oon @ MCsoemprany .Partial R* " <a F | | <a pr 000074 a me Pingo) J-- ws on -- _-- -- sri wars Mrs oe oe A r piA tmeaso-- p ton oss | | Parameter SE ae he oan - 00% om oe on oon oz om own - - won ome wane am wn ome puie Partial com o = wo ator " = on = on " 0 Pp " a - " | 000075 sn S pror eT onu--s-- Ss I se pave Cm oso ome roa om i J os ows <aon - oss our " a os ons u Greer oe om - -- oor om = Tiger - - J wen AdiRI= 16 *Naturallog. 3sMCormpany Partial - ! <a | wn on on wo 00 0076 | re Multivariable Regression ModelofAlkaline Phosphatase*byPFOSand PFOA eso | | ee -me m Sw c n n. Ye mms o eeIemBE s BE n NE Ri=.18 AdjR*=.16 000077 | | Tues Mu{loriAarntedRergGyreeasnssdioPDneoceatnlr MoEaftxeAplBkaalltionsetVhsasPrpanhiesispaasnetsb,yTOF S00 Nee Sumeans rg Pubs 3M Company J Apres :J Paameter SE pale Patial B 370 ois <r i or ows os Pr on Production fb eso) oon oom PF <a Awerpecsr oir oo <0 wo ne ous oz <a Bi "oot oot Fl pr Gipsy a2 oor pr Drinks/day -0024 0016 14 <o1 ! Yours Worked "2 om a. <a Tgeeridst ose oo oes en ANdejRt?t= io1g6 000078 Tbe? MuliavnrdiOstihcerRPegoretssiionEMxoldaenltorfyGGVTartblysPROS for Antwe5r5p0a0nMdDeetcaatuSruMnaillaEnmcpeloryoegsrPaamricipns, P3eMtCromeprandy | nee i Pros Parameter SE L246 om aos oo pvalue Partial R* <r i 2 Production Job (yes/no) 0003 0059 96 <1 ! AmverpDecaur 025s 006s <omn @ I 000s oo ss <a Ba as our 5 [erm---- Drinksiny Yours Wort ous ous on ons om aor PY o oe as <r Tagheendest 024 00s <a os RA"Niju=wR2r5elio2gs 000079 | ot Reoncr s Table 48 for AnnSd0e0Ol0endinDdecaaaSMEuaxrtpeEimlrpiayaPprnoVegearrPaeamah ins PIeMCotmeprany. | oom oon " py | Parameter SE_ Incr 1205 ozs i Pro om oo Production Job ges) "oo 0x0 Jr---- os ous nt [re---- Dinky Years Worked Tigheeidest aces or om ou ous om oa oo oa o0ss <0 p value oo El 003 iPartial R* o <a 3s 2 a 2 " pr <omn w= 25 fchitid 000080 LL ner Fro mou Pocono i) j---- ae a Cipeesiny Dray YeasWorked erst ---- Ria28 ANdejwR't=o2n3 Tes M{iorvAmaerRoyegaernedsaDioin dneeMlEoxkocfpGlOootTrebVsyaPFRnOasSisnrdsPFOA ede Sues Poa Pameter se 1246 oa aon oon aos om "ons oo os aos ooo aos aos aor oo oo at oon oo os oa ooss -- pvalue <oon a ~ 2 st 2 wz " <n -- P3a4Ccotmprueay Partial R* . pr o 0 o | <n 00008] | 081 | oo. -- - on -- ro RB=i3s R T wea_A pp on fttynid LE Panmeter se value Paral R? -- . . -- -- p.s .. || --- -- 5. .. - --- a. -. | 00003, | | LL Intercept rere Age -- --i WHry Parameter ms ReE e, ~ SE 0133 value. <.0001 I" - 0003 0002 x hoo - - htoo ." sem Partial RY . . <o1 " .. 0000gg abe s2 fMo AievrtaeanrdRBeDgereescnoniEcxepeaElmotrfroyAVsSaTrFbiayeiPsFnOtA, So ee Sunes rg Parameter SE pvalue. | ner ams om <0 Fron aos oon wn PrionJb (ein) om oo 2 AnverpDecau os ons oot re om oo a a ow aos st Cipretesay 00m ooo o Dry oost oon on Yous Worked aos om os 5 fr oon ons o | RRN'uo=r09oiof ccorop .Partial B a <a pr <a <a a <n 000084 oceosm Tbe ss Mli(ovraAitmOiyRreagedsDPioeotcnenaMtodMEeleaxf EApnSpTol"obtVyeaPrPRaOalScsstdsFROA Sood umesFog | Sem te . . _ Parameter SE ner ams om ros os oars rox oon oo Pocono in) oom oon pyalue Paral RY <oon i <n <n a <a ne oon I 5 pr a oom ooo 0 <a Cigaretiesday, -0003 0001 " <0 ) Dray oon oon on @ YeasWorked 000s ooo o o a erst oon ons o <n= | NwAerreog 000085 Pcasosmipoanny | Table st Maliuvnadrtishbrl RPeotgernetsisailoEnxMploadnealtoorfyAVSaTrSisbbyesTOF {for Antwe2r0p00sniddDeesctSrMvateelEnmcpelPoreoegrPaamricpas, Co mn | Paw oterept ams Tor oon Production ob ese) ~oon AnverpDecar 0105 P SE pukeR om <o00n - 0009 Fd o oon 6 <a 00% 0 @ J BMI 0.002 0.004 st <0! Cipseesiny 000 oon o <a . Drink 00s oor ws @ Years Worked 0008 oon " o Tigerdest aos oos o <n or Sing 000086 Tess | orMAid ovarD RecgenVEMipEoootnf AseVLTPbnoytPenSt, che Sues Peron Parameter SE pualue [i 1a oes <a os oon os 2 Pdi oh yesh) oon - o Aner om oon <a " om ons on ous oon <a Cimsedty "oom om ons -- owe oon Ves Worked om om 0 Tons ow ous <a Mas R=. 27 w-- w Pais . o p o pe " o <a <n os 000087 --_-- Intercept Pron Production Job (sie) AnwepDecar xe i Cipmreesiny Drikatdy Years Worked f-- R= 27 Nav iog Table $6 MuliavnadrOsltchRPeogteenstiiaolnEMxopdlenlsoofryAVLaTriabbylesPFOA {or Antw2e0r00nMdeDdeiccaatlurSMuraveeillEamncpeloPyreoegrPaamrticipants, Pum SE puke 1761 0.165 <.0001 00s ous n oo oon st 0186 oon <0 0002 0003 " oo oon <oon -0007 oon a0 ~0005 ons 5 "0004 oo 1s 01% oa <oon sar Pa . <n <0 o <or 2 o ; <0 <a os 000088 toes MalfowAarnesd ROeparedsDPieoonncitdMeElexofEpAorsLgVaPTraEaOpl*Ss1tnsbd,PFyOA | S00 tl Suerongram hme SE pale J 1251 oes <n ros ao aos Fron aos om 1s Facion Jo es) oon oon EF Anerecan os oon <oon ne 002 oon 0 oi os ooo <oon Cieresty 0007 oon oon ---- 0006 vous YeasWoked "aos oon n Traore om oon oot a ANdajRt'=i2o6 ectotmepr PartiaRl . a <a <a w <a 2 <a <a <a os 000089 Tae ss Muld ia RePO gorneissioEn: xi patofd AVLaTrbse byiTsOR for AneSr30a0ndMDedeicltSMuomtEeroogrFaairs, | en a ws co Co Pumeer SE p value nen 196s om <n or oo oo Prodcion Jb sh) 00st aos 2 | ae om oot BS a oon I~ @ ----" 0007 om woos Drinks ont ons @ Vers Worked "0002 oo " Tred oi oot <ao0t Po Partial B <a. <a o on } pr <a os oRR= 32 000030 oo neers ros Proecon ob sin) AntwepDeca re a Cipresioy Drnstay Years Worked Trends ee Riz. 2 Tae MfooirvArweeORenagrsnedsDPsieooncnMttoMdEextpofaETnoaoatysBVioallipsnnby ,ROS 0 ete Saves Frog teme pie os ous <oon "oon oars as "00s os o 0 oo <r acer 00s = 000s ooo os ow <1 0s on M 0.0002 0002 94 aos oan 5 rSsceotp Pa . o i <n <a <a <0 <a 000091 eso Milfot eAptaisOrond DSneocmot idofBTemoporlyaBVcauttsiby,PnFO caoSmeogera J plac |J oa0 ores <omt ron "000 aon 7 Podion ibe 0m aon " AnwerDecs 06s ao pre " I oo0s " p" ~ao0s oon 2 |-- 0008 om <om Drinks/day Vea Worked 0005 0.019 acon oon a80 Treat "oo oon 2 v3MCsompeany PartiaBl . o o " wn wn o <0 } <n <a Ri=29 at, 000092 Co merce Pros Poa Producion Job esi) AnmerpDecar Ae a Gigaretesiday Drinkslday Years Worked Tiglyerdes AR=R29= 20 "Nowra log Table 61 `MolivarfoabeAnRatenwdesrOipthoaennrdPMDoaetdcenaett!iuaorlfaETxoetpallaEnBamitpollrroybyieVaneriPbaabyrlieFcs:iOpaStsa,nd PFOA 2000 Medica Surveillance Progam ewes SE pale 0209 om <oo01 018 0016 2 [3 003 Ea ~00m0 oon 06 026 00% <o001 oon 0003 5 -0005 000s x 0008 oor <o001 000s oo 8 00002 oom 5 0016 oan 56 nSeMsCtomapany Pui R* - 0 o o 16 <or <on . <on <0 <on 000093 Co eran Tor Producion ob eso) AverpDecar Ae al Gipsy Drnkatay Years Worked Tigoordest R'=20 ANGaRIw=2io1g Tae 2 MulivranbdleORtegcrePsostieonntiMal EoxidoafnTetooltryBVairbiiesnbyTOF for AntwSe0r00ndMeDdeicctSMualneiEmlploPyreoegrPaamicpans, rmeer se palue 020 0144 <onn ~o0n oop = 0084 oo 0257 oom <omn oor oon ao 0005 oo i 0008 ooz <om1 os oo Ed oar ooz 58 00 oar rcaosmapar Partial RY . a 6 <or <or ks . <or <or <or 000094 Tee) MaliivnadrOithhieRPeogtreenstsiailonExMpoldaenlatoofrTySVHariabbylePsROS forAntwe5r0p0a0nMdeDdeicaaltSuruMravleeEimlplloPayroengercPaaemricipats, ame SE puke Pros oot 003 Production ob (eso) 0109 oom 1 AnwerpDecar os ooss o Are 000s 00s 36 BM ~0005 0009 56 Cigareestiny ~0005 oo un | Drinksiday 0057 | oor "" Years Worked ~0008 000s 5 Tilyeridest 0204 0061 on R= 07 Shion PCoomrpaanty PwlR <or <or @ <0 <or <a } <0 <n 000035 jo A MoliosmeerRFeesoanaMgomdionfeTvHFobyarOrrA. Tn soos ogi J Cs pue ener asm om wou oars oon 5 Sot om oars Avene os oom on I" oo oom | no os ome 5 ny os oms nw pony ooss oz etn Years Worked oan om 0.008 0.005 13 on Ri=. a Sion Fcoomp Parial B . p pe Pp an <n a "<o1 000096 Table 65 MaltivariaabnledROetghreerssPoitoenntMioaldeElxpolfaTnSatHo?rybVyarPiFabOlSesand PFOA for Antwe2r0p0a0nMdeDdeiccaatuSrurMvaeliellEamnpceloPyreoegrPaamrticipants, | tne as wn 0 Parameter se pale PROS 0007 0036 8 PFOA oois 0029 5 Production Job (yesino) 0096 ost 2s Anwerp/Decatur om 0089 os Ase 0006 0006 3 BMI -0005 0009 51 Cigaretestday -0005 0003 n Drinkslday 0056 0002 a8 Years Worked -0008 0005 13 Trglyceridest 0200 0062 01 RAG=R0=05 Naural log FaagMeCdeoanlpu2r1y .Paria B <0 <0 <0 <0 <0 <0 ; <0 <0 <0 2 Table 66 MalainvdaOitbhleer PRoetesnstiiaol nExMploadnealtoorfyTVSaHribbiyesTOF for Antwe2r0p0a0nMdedDieccsatluSrurMvaeliellEamnpceloPyreoegPaamrticipants, oo vee SE puke Imereept -05% os 10 Tor 001s oot 4 Production ob yesine) 0097 [ 2s AntweryDecator m 0088 05 Ae 0006 0006 EY a -0005 0009 5 Ciguretiestay -000s 0003 n Drinkslday 0056 oo 1 Years Worked -0008 [es Triglycerides 0201 0062 oo Reg "ANdajtuRr}a=l l0o5g PaCeosmpa1ny Pek - o <or o <or <ot <or ; <ot <ot o 000098 Tale 67 forMAalnaitnvdwaeitrshbalrnedPRDoertceeansttiuiarloMEnaxlMpelondEsemtlpolorofyy4Vee+raPbabyreiPcsRipOaSnts, 2000 Medical Surveillance Program PasoCnoalury oo | J. wae 260 SE oo pwe <on Pw . Pros -0003 0009 a <ot Production Job (yes) -0003 002 51 <0 AntwerpDecsur oon oo o <n TM 0003 0002 os <or i 0001 0003 <on Cigaretestiay 00009 00009 2 <a } Drinkatday oo oor o <n Years Worked 001 000 3s <n Thycerides 00s oor? <0 R=. 2 fin. - 000099 | RrEeener -oo wl Pemmeter SE value " aL om Partial R* ARG'R=.I0=3 01 000100 eens pros won Production 0Geshe) AverDecar ree Bi Cipeetay Dinky Ves Worked Triglycerides em Nog AiR =<01 Tew Mo{orlAvOatRsengdesPDiooennctMtodMEaextofpo4o+esbsyVoFrFObSaissindrPsROA S000 Medel Suen Fog Parameter SE pvalue 26 ooo coon "0003 ooo " oat os 5 "ooo oo o oon oo " "000 02 ocr os o ows oom 2 Er oon " owl aon 5 -0018 LL 29 ferrit Partial RY i pr pr <a on <n <a pr <a <a <01 000101 Table 10 MualnivdaOrtihbelrePRoeegnrteisaslioEnxpMloandaetloorfy TVa4riabbyleTsOF for Antwe"r2p00a0nMdeDdeiccaatuSruMrvaeliellEamnpceloPyreoegrPaamrticipants, PuScMlC0ormopra2n1y | p-- i" w- ero weer SE pyalue Panial B TOF 00002 0006 9 <0 Production Job (yesno) 0005 00 = <0 Amwerpecatur oot0 oon <0 Ase 0003 [2 0 <0 BMI 0001 [2 o <0 Cigaretestday ooo 00009 a <0 . Drinksiday 0024 ooiz o <0 Years Worked 001 0001 a <0 Trglyeeridess -0019 oor a8 <0 R=03 A"NRaw'a=l<lo0g1 000102 | TS Tae for AndtweersndhDenct MExlpelaEnamtpolroyyVeearPiaesrca S00 Midi Surelnc Program SR SE pvalue | erent I oome <a pros 0008 ome ProductionJob (ene) 000 009 a AnwerpDecaur "om oom = ne 0003 oor a 0003 om 1 Cpeesiay oom oonoe n Drnksday ous 000 56 Years Wake oom oon a Tigherdes oo oot 5 ro Paral RY . <a <a a <or <a . <or <or <a RA=aR%eo 000103 Tab 72 fMourlAinvtnrwdieaOlteaeRreDgPeecstaitoeunrMMEoxdepeaElnmotpfolrFoyyeeVeaP4raiberyscPFaO,A 5500 MedicalSurvPriogream oo Parameter SE pave | Intercept 0299 0076 "0001 Pro 0006 0006 at ProducionJob (eso) 002s 009 i AnwerpDecatue 017 oo " ae 0003 om a 000 omz 5 Cpmeresdsy 00 00s xz Drinks/day 0.006 0010 53 YearsWorked oo our gerd oo 0014 El [caotimvpeu Partial R* on <on a <or <or . <01 <or <or Ri=07 "ANdajuRr}a=l i0og4 000194 Table Ts MalivarisbalndReOgtrheesrsiPoonteMntoidaellEoxfplFarneaetTor4y*bVayriPabFlOeSs and PFOA for Antwe2r0p0n0dMDeedciactauSruMraelielEamnpeloPyreoegrPaamrticipants, PeSM0C8om0pa1n2y1 Puameer | Intercept 0299 Pros -0005 PFOA 0006 Production ob (peso) 00s Anwerpecatur -000 Ase 0003 BMI -0003 Cigaetestday -00009 Drinkslday 0006 | Years Worked 0002 Triglyeerides 0004 SE pula Puri] B 0076 01 - [ 96 <0 [a = <or oo 2 <n 0210 a 0001 o a [2 B <0 00008 7 0 0010 2 <0 0001 ) <o1 oot mn <0 RA=G0R7= 04 | "Natural log 000105 tcp | EsCrt Eaonar-- _ _ Parameter SE mee oonm aeoss nimi ams wn pyalue. Partial R . on" on o-a "Jann Io"n ". an | aunnr Coawasn faoe Njs w Cre ou on on Twa w ow w R=. % AGR'= 04 000106 Table 75 MulivaanrdiObtlheerRPeogtreenstsiialonEMxopdlealnaotforTyHVBaRriabblyesPFOS for Antwe2r0p00anMdedDieccaatluSrurMvaeliellEamnpceloPyreogeraPamr.ticipants, Pa5gMeConpun12y1 | _ween PROS umseems oSoEn p<uaolumc Puri B -0003 0004 "0 Production ob (yes) -0006 0010 55 <0 AnwerpDecator -00%0 oon <0001 30 I -0008 0008 50 <0 BMI -0001 ooo 2 <0 1 Cigaretesiday -00007 00004 an <0 ; | Drinkslday -0015 000s 00s on Years Worked 00002 00007 m <0 Trglyeerides 0003 0008 as <0 R= 3s oc pd 000107 Tbe 76 fMo AimoevdrOay aenRdePDgtrenecsioaoniEeelpoEoTlnHBoVRaPsebaysiPFnOsA Sooo Mec Sunes gm I Pumeter SE palue. | Intercept 3.589 0041 <.0001 Fron 00 oo Prcion J ee) "00 aon Awe "00s oon <n re 0000s aooos " a "0001 aon ] pr---- "000 oo 5 Dry oois 00s os Yous Worked "00002 oon n Tete "002 os % Rpio=3r5 | Natural log. r[iro Partial B " <n FY <a pr pr a pr pr 000108 | Taben | MolifvoarrAinbnldeRreOgrarensdsciDoneiMcoltdeMlExokpfaTEnHtmBoRonytVbeyaPFraOaSihnsntdsPFOA S00 Nhe Suen gm _ Parameter eens ss09 Pros "aos Fron "a2 Prion esi) 000s AvepDecae "aos ne "aces a "0001 Cipuetetsy "000 Dri oois Yeas Worked "ome Tred "oo on Not AGjR}= 34 SE pvalue aout <0 oms = aos " oon " oon <onon oooos a oon oot 8 ose ot 00007 oo Pasar Partial R i on = <n pr } <n on <a <or 000709 Pastor Ter | (aMAoolvta RFeSrsetionniMgemEl oymfTpyHFobEay TnRO,F Tnen Parameter SE pvalue. Partial R* [-- asm oon <omn . - om os 0 Poscimiduh 0m om on sre om ons <a " oom aos - en wa aon aon on -- oom oom M on Drekutey oars aos TM o ------ "oom oon " on T0 Tiaterr oe"moon 0 aon 7 a | pSoirig 000110 Taber foMr AanitnwlderiiphsanedRPDoeetcgeaenttsiuiarloMnExlMpeoldaEnemaltpoolfroTyyIeVe*arPbsabyiicePspEaOrSs, S000 Medical Surveillance Program vee SE erent 129 ooss pros 0006 0009 Production Job(reso) ~0009 oan AntwerpDecaur 008 oo I 0003 oon ar ~o0m1 oon Gipsy ooz 00009 Drinkaty 0008 oon Years Worked om oon Tages -oo2 0016 pve <0 a 5 00s p 5 2 " a 1 R=10 Shir Faro PamalR . o <o 0 <n <n . <on <a <a 00011 Table 80 Mali`vanadrOitshbelrRPeogtreentsisailonExMpoldaenaltoofryFTVIa*riabbylPesFOA for Antwe"r2p00a0nMdDeedciactauSruMraveliellEamnpceloPyreoegrPaamrticipants, Pu5cliCioomnpiaanly Peer SE palo Panial Inercept 129 oss <0001 - PFOA -0002 0007 mn 0 Production Jb(eo) -oo12 oo 36 <0 Antwerpecatur -00m oo 0006 0 | re -0003 0002 3 BMI -000007 0002 8 <0 Cigaeteslday 00002 00009 0 <0 . Drinklday -0008 oon a <0 Years Worked oor 0001 "a <0 Triglyeeridest 00m 0016 15 <0 - R= 10 A"NdajtRu'r= l0o8g 000112 Table 81 MalivarsabnldeORtehgerresPsoitoenntMiaoldEexlplofanFaTtIo*rybVyaPriRaObSlesand PFOA for Antwe2r0p0a0nMdeDdeiccaatuSrurMvaeliellEamnpceloPyreoegrPaamrticipants, _ Parameter se pale terept 1239 oss <.0001 Pros 0006 0009 49 PFOA 00002 0008 9% ProductionJob (yesno) ~0010 oon % Anwerpecatur -00m oon 007 | Age -0003 0002 Ed BMI -00001 0002 9% Cigaretelday 00002 00009 2 Drnkslday -0008 oon " `Years Worked 001 oor - Trigleeridest 002 oot6 a RA=G1R0= 08 Nawal log Pag5eM1C2o0m0pa1n2y1 Paria B N on <0 <0 06 2 2 ; <0 pr on 04 I A oenan-- ELIA | pePaneer SoEns pcaoloen or i mitt oon - Aca po po om 1 oo wr o TM -- - om pt " - aeries - oon om " " cen .Partial o I" o on on | Mn AR=G.R1I=0 08 000114 PMaCasmpiang | Tables MulainvdarOiarle PRogtrenetsiailoEnxMploadnesltoof3y V+arbaybcPsFOS for Antwe2r0p00anMdeDdeicaaltuSruMraelielsEnmcpeloryoegerPaamricipats, Parameter se pase Paris R* Inereept wn oom <oo01 . pros oot 0007 0 o Production Job (yes) oon oois o AntwerpDecatr 009 5 oon <oo01 o Are -o002 ooo a <or Bm 0005 0002 o Cigaretesiiay 0003 00008 on o } Drinklday 00 0009 os o Yeus Worked 00006 001 <or Trgyerides 002 oon 15 <ot Ran | Siniios 000115 een ron rotons) Avena ow pits Dona Yer Wakes eid og Ri=13 Ten Nor Aovieee:DRPeeslonpNlkoEdigofe3VaoFbtyoPoFsOA, esot Pog Pameter os pave m om <a oats om a ons oo a oi oa pr om om ows om om ous on om om ws oor om n oon oan cirrop Partial B <a wn p <a 000116 Intercept pros PrOA Production ob (yesioc) AntweryDecatur ae Bi Cigarettes Drinkstdy Years Worked Tigyeerides RAGeEn= 11 "Netra log Table 85 MultivariaanbdleORtehgerrePssioonnMiodEexlpolafnTa3to*rybyVaPrFiaObSleasnd PFOA for Antwe2r0p0a0nMdeDdeiccaatuSruMvaelleloEnmcpeloPyreoegPaamrticipants, rwmee 470 0009 oor oor2 0109 -0001 000s 0003 -008 -00006 oon SE puke 0073 <.0001 0008 2 0007 0 oot E 000 <o001 0001 3s i om o 00008 oo 0009 0 0001 oo14 [5aMCnosnary Pail - o <or <ot <ot } <0 <or | ner Tor Ss sve ne oi ---- pony Yous Worked geen R=13 Seog | tegeTnesot 008 E EE Tony kotedaStats , J om Parameter a SE <a pvalue oon oon TM oon oo - RE oom com om om oon oon a oars sour o oom oom os "oor - % oon ao 2 Partial R* pe po " " on wo 000118 rSMaComrpany Figure 1. Linear Regression Model of Trigigycerides by PFOA" for Antwerp Male Employees, 2000 Medical Surveillance Program = 55 . 5 LC . En#] LCieade. wTidl . enh I. `Summary of Fit RSquare i" 0.029 ws Analysis of Variance Source Model Error C Total DF_Sum of Squares 1 1.863 204 61.193 205 63.056 Mean Square 1.863 0299 ParameterEstimates __F Ratio 6.211 Prob>F 0.014 Term Intercept In PFOA. Estimate 4.695 0.073 Std Error _t Ratio Probalt] 0042 11143 <.0001 0.029 249 0.014 *natural log 000119 Pag3eMCo11m9p0fan12y1 Figure 2. Linear Regression of Triglycerides by PFOA* for Decatur Male Employees, 2000 Medical Surveillance Program TM 5 Fi LElAe. 5 LEN Ez - 2 is z a oo .. " SL is tat ERE EE CIC wu `Summary of Fit RSquare a. 0.028 - Analysis of Variance Source Model Emor CTotal DF Sum of Squares Mean Square 1 2.164 2.164 213 73.969 0347 214 76.133 _F Ratio 6.232 Prob>F 0.013 Tem Intercept In PFOA *natural log ParameterEstimates Estimate Std Error_tRatio Probl 5.052 0041 12227 <0001 0.098 0.039 2.50 0.013 000120 Pag3eM 1C2o0omfp1a2n1y Figure 3. LinFeeamraRleegrEemspsliooyneeofs,Tr2i0g0ly0ceMreiddiecsa*lbySuPrvFeOiAll"anfcoer APnrtowgerrapmanc: Decatur 7 5 . "os ul Wn eaeh | nlSdo AeNA T | s wr `Summary of Fit RSquare 0078 SMooudrecle Error CTotal Tem Intercept In PFOA Analysis of Variance DF 1 Sum of Sq2u.a5r1e9s Mean Sq2u5a1re9 _F R8.a0t1iQ 95 29.877 0314 Prob> % 32.39 0.006 Parameter Estimates Estimate Std Error_t Ratio Probalt| 4690 0081 58.14 <0001 0091 0032 283 0006 *naturallog 000121 Pag3eM C12o1m0pfa1n2y1 Figure 4. LinearERmepglroeyseseiso,no2f0T0r0igMleydciecraildeSsu"rvbeyilPlFanOcAe"PfroorgCroatmtage Grove Male 7 5s . " ST BL FN gf I o = NETe " an J 15 : : n SAT5 AA Tas wn SummaofrFiyt RSquare 0.008 In Source ErMrodoerl C Total Analysisof Variance DF Sum of Squares Mean Square _FRatio 1291 504.245512 00.442512 Pro1.b0>7F6 130 54.704 0302 Tem InItnePrcFeOpAt ParameterEstimates Estimate Std Eror_tRatio Probl 50.003222 00.003517 881.0044 <.00300021 *naturallog 000122