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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 Start Date: 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., Ph.D." Michele M. Burlew, M.S."
Jean M. Burris, RN., MPH." Jeffrey H. Mandel, MD., MP.H.!
Jeffrey H. Mandel, MD., MPH."
1. 3M Medical Department. 220-3W-05, St. Paul, MN. 55144-1000 "(Corrections made from previous version)
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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 percentofthe eligible employees at these two locations, respectively.
Seventy three percent of the participating Antwerp male employees and 75 percent ofthe
Decatur employees were engaged in production activities. Only 12 percent of the
participating Antwerp female employees were engaged in production activities compared
1063 percent of the Decatur female employees.
Employees' sera were quantitatively analyzed for PFOS
(perfluorooctanesulfonate), PFOA (perfluorooctanoate), PFHS
(perfluorohexanesulfonate), POSAA (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.
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P3aMgeC3oomfpa1n2y1 Mean serum POS 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 ppmand 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 theirjob 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/mm?), white blood cells (WBC, 1000/ mm') and platelet count
(1000/ mm); 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/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 stimulating hormone (TSH: pIU/mI): serum thyroxine (T4; g/dL);
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P3aMgeCdoomfpa1n2y1 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 (ETD.
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 wasusedto 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 vids a modest positive association between PFOS or PFOA with cholesterol as well as a stronger positive association between PFOA and triglycerides. These i" 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, itis unlikely the observed positive associations between PFOS or PFOA and lipids are causal. Because of the potential confounding positive association with serum triglycerides, ths 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 (.g., hypothyroidism or
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P3aMgeCoSmopfa2n1y hyperthyroidism) for thispositiveT3 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 suspectedto 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.
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INTRODUCTION "The 3M fluorochemical medical surveillance program is conducted on aroutine.
`periodic basis at the company's Antwerp (Belgium) and Decatur (Alabama) fluorochemical manufacturing plants. Prior to 1994, total organic fluorine was measured rather thananyspecific fluorochemical analyte. Serum perfluorooctanesulfonate (PFOS) and perfluorooctanoate (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, 19983, 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;
19993). 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
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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 etal 1999b). This finding suggested that the distribution of
Serum fluorochemical levels observed in the prior voluntary medical surveillance
program likely reflected the distributionof 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 2001; 2001b; Butenhoff etal 2001: Gilliland and Mandel 1993:1996; Haughom and Spydevold 1992; Olsen et al 19982: 1998b; 1999; 2000; Pastor et al 1987; Seacat et al 2001a; 2001b; Sohleniusetal
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 a1 2001a: Sohlenius et al 1993) and primates (Seacat et al 2001b). PFOA has been inconsistently reported to produce hypolipidemia in rodents (Pastooert al 1987;
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P3aMgeC8oomfpa1n2y1 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 19983; 1999), the present study examined associations for both PFOS and/or PFOA as well as a calculated measure for total organic fluorine (TOP). Longitudinal analysesof employees who participated from 1994/95 through 2000 `were not analyzed as this was a focus ofa separate analytical report (Olsen et al 2001).
METHODS `The fluorochemical medical surveillance program is available, on 2 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, 20010).
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`Hematology, Clinical Chemistry and Urinalysis Alina 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 glutamyl transferase (GGT, * IU/L), aspartate aminotransferase (AST, IU/L), alanine aminotransferase (ALT, TUL),
total and direct bilirubin (mg/dl),bloodurea nitrogen (BUN, mg/dl), serum creatinine (mg/d), 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. _
ThyroidHormones Six thyroid tests were conducted by LabCorp (Kansas City, MO): thyroid
stimulating hormone (TSH; pIU/ml); serum thyroxine (T4; ug/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 determinedbyan immunochemiluminometric assay (ICMA). T4 and THBR were determined by acloned enzyme donor immunoassay (CEDIA). FTI was calculated by multiplying T4 and THBR.
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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 In. (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 limitof 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 L11 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
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3M Company Page IL 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 PEOSAA 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 (POS (64.79%); PEHS (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 Analses Serum PFOS and PFOA levels were the predominant fluorochemicals as the other
five analytes were measured at considerably lower levels (Olsen et al 2001b; 200Lc); 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
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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 asa 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 activites
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
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Pa3gMe CIo3m0pfa1n2y1 serum PFOS and PFOA levels; were significantly younger; had lower mean BMI; 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 comparedto 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 fashionDecaturemployee data are provided in Tables 13-24. The Decatur data also include employee urinalysis results.
Antwerp production male employee data (n = 150), stratifiedby 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
Towest 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 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 1 and 3 quartiles.
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Pa3gMe Cloomfpa1n2y1 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 ameanof0.13 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 of0.06 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 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 2:31 - 10.06) compared to 0.55 ppm mean serum PFOS level in the lowest quartile. There were no significant mean demographic differences
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between the four quartiles and the only clinical chemistry test that was significantly
different was ALT (Table 13). The highest quartile had a significantlyhigher mean ALT
level (44 IU/ml) compared to the 1 (33 TU/ml), 2* (32 TU/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 1.6 ppm (range 1.00 - 2.95 ppm) compared to the
lowest quartile meanof0.19 pp (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.
I"
Among the 48 Decatur production and non-production female employees (Table
21), the highest quartile had a mean serum PFOS levelof 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 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).
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.
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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 percentageof 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 distributionof2.69 ppm (range 1.69 -- 10.06
ppm) compared to 0.27 ppm mean (range 0.04 0.42 ppm) comparetod 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 (see footnote to Table 26). In the lowest (1) 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
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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. Forthyroid
:
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 asimilardistribution 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 fo the highest quartile. Also observed was a lower
mean GGT and blood glucose level in the lowest quartile when compared to the highest
quarile. There were no thyroid hormone differences between the quartile distributions
(Table 29). `Summarized in Table 30 are the combined number of Antwerp andDecatur
`employees (and percentages) who had hepatic clinical chemistry tests above reference
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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 comparedto 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, BMD.
`Because the higherliver 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 (ye=s 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:
(TOP).
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 | 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
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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 thatjointly 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. PFOSand TOF were not significantly associated with HDL, but PFOA was significantly negatively associated (Tables 35 through 38). As to be expected, BMIand drinksper 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 predictorthan 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
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(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 RY).
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 knowledgeofthe
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 PEOS 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
000152
Pa3gMe C2o1mopfa1n2y1
PFOS, PFOA, PFHS, PFOSAA, M570, PFOSA andM556 levels measured in the 2000 fluorochemical medical surveillance program with their workplace operations in Antwerp. (Olsen et al, 2001b) and Decatur (Olsen et al, 2001).
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 1998; 19992).
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 etal 1987; `Seacat et al 2001a; 2001; Sohlenius et al 1993). On theother hand, there is inconsistent evidence for hypolipidmia with PFOA in rodents (Pastoeotr 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
Pa3gMe C2o2m0pfa1n2y1
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 beenassociatedwith 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 | through 3 for the Antwerp and Decatur male and female employees.) We therefore believe that its highly unlikely that these are causal associations observed in the 2000 fluorochemical medical surveillance data between PFOA and serum cholesterol and triglycerides.
Previous toxicologicalandepidemiological 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; Butenhof? et al 2001; Gilliland and Mandel 1996: Olsen et al 19984; 19993; 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
Pa5gMeC2o3mopfa1n2y1 quartile withoneor 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 (235%). 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 occupationalor non-occupational exposures. An analysis of episode of cares (Olsen etal 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 episodes of care regarding cystitis was similar. No differences were
000155
Pa3gMe C2domopfa1n2y1
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 ofemployees 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 s the focus of aseparate 3M investigation (Olsen etal, 2001a). Although stil 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 andlor PFOA levels with clinical chemistries, thyroid hormones or hematology results. Because 3M has announced a phase-out of the production of perfluorogctanyl 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
P3agMeC2o5mofpa1n2y1 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
Pa3gMe C26omopfa1n2y1
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fAalceilxiatny.deMrinBnHea(p2o0l0i1s2)(.VINM)o:rUtnailvietryssittuydoyfoMfiwnonrekseortsa,em(punlpouybeldisahtetdhree3poMrt)C.ottage Grove
MAilnenxeaanpdoelriBsH(M(N2)0:0U1n6i)v.erMsoirttyaloiftyMisntnuedsyootfa,wo(rukneprusbleimsphledoyreepdoratt).the 3M Decatur facility.
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00159
Pa3gMe C28omopfa1n2y1 Sohlenius AK, Eriksson AM, Hogstrom C, Kimland M, DePierIrWe (1993). aPenrdflotuhoerrooaccttaivnietiseuslfkonnoicwnactiodbies aafpfoetcetnetdibnydupceerrooxfispoemreoxpirsoloimfaelraftaotrtsyiancimdoBu-soexildivaetri.on Pharmacol Toxicol 72:90-93.
00160
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1
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000163
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
Alk Phos
GGT
AST
ALT
Total Bilirubin
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Free T4
kel
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IE 13 am oM-28 2% 200 0 0-4: AMIR 106 sees SH Sam dm-nn
A mean 0 G0 ees m0 eo oe eo ae oo
| Comene 1 OR
Wer 08-17 14 10 22 081S0 1 ue es-is
Np er A oficicaesmPl<y05,Boner (Dun) et)fr heses ofbe 0AE
000174
Table 1
3PaMpeCdoompfa1n21y
Thyroid`RDeescautlutrsMbalyeQuParrotdiulcetoiofnSEemrpulmoyPeFeO(SDNi=st1e6b1u)tion*
|
A Que1 112.40
Quite FM i l
($V12
40)
Tage
TH ws 24 tok oses3 24 08 ap 02-E
LE
a sr 1 aewn 8s Gs 1s ome
Mem 10 G0 01 0613 LL 02 oamie
mus
seme me mw s-be
J EE TEI
mm be 24 03 azn 2s 2s os deed
mwwe
n25oeseiTgabflcea1n3fyodrisfeerruemntP(R<OS0qu,arBtoinlfeedrirsoinbia(iDounna) es) can valu.
VenQuMriellea3 04S-p41) Wome Men QuMietne 40S4204_0_)funic
24
S15 08ee 30 24 04 asnd
ass 17 arms ass s1-114
ML 02 0rnis
0 or 08-13
mW au gem ns 06D 91-190
EE
26 25 0s Asus mo 19-34
: 000175
Table 15.
HematoDleogcyatRuersMlaslebPy QruordoiEfmSulpelrcoueymtePe(FiNOS=o1D6in1s)tibtiont
TiQSeue=3, Range Wa MQuei 2dSvb=o) TageJ n Mtn 50 Home wr ws 2 wu 6 6 2: em 6 6 1 wR Wm 1 3 09 mama Si 2 0a Ma-ma isa Se 10 mi-PS Mc a5 so o> 4005s So so 03 Aiese sa $0 IB 41-60 WBE 6 Gb am 6 se be M2 es S915 4lme des me Wo 6 meow wm ewe om mw 0 mem osiiI fnty ie snPr <0c5,uDo eifaernes bDioen) es)ms vs:
aw cbormipdu
es
Wen QMueessi=SdOo) Reg
6 8 u 9%
12 isi of no-les
$0 SO. 04 Da-sy
es
13 28-ns
wm 6 mow
000176
Table 16 UrinalyDseiscaRteusrulMtaslbeyPQruoadrutcitlieoonfESmeprluomyePeFO(S=NDi1s6tr1i)bution
Pa3gMe dC5oomfpa1n2y1
Quarile 1 N(%)
Quarile 2 N(%)
Quartile 3 N (%)
Albumin
13
26
13)
Blood
38)
4(10)
410)
Sugar
3
-
13
202)
Number of Employees: Q1 = 40; Q2 = 40; Q3 = 41; Q4= 40 *See Table 13 for serum PFOS quartile distribution
Quartile = N% 10)
13
0
000177
Pcaoolmi
Tae 17
Clit becatorMilReeNuosnbPryoQduucatiiolnoEfmSplcouymePe(QRuNOi=SsD53i00)s8ieb1u0ton EIS :
B Qeume 0o12m13swanie owPRowinoi w on_noe aw
etARwTan ve om apm
Le en wn Leo om en
Tew or Oe
ou aw
awosan ow ome
oe wn as owe os om on ow-in
ma
Me wa awn
43
J
um
am wa I wR
ae
es
a me me soma
a won wma
am
Wa a msms we me mow
wr me
mm we me wend
s J a mow sweo
ne we
Ly Ve
em eas
1 em oe mo oom
ew
ae wm ew ww wen
wma
oa wm mm
ws wm wwe eo
Ws am wm mm em
a ame
maw
wm
aw aww
ae ow momo
ws
we TF
sa ww
m om mmsmWow?
ha a a bw
we mo ww
omow mom
A
oe een eer
0 ant
J me oor om sea
wre
or om ee
a
oe ems Ns am
wo ww
om ww um
Fo to wear een we mow pen
Woe ww
uma wee
8 wo 2% -166
lucas
""
9
B 6 mete
tea)from themeanofthe 1% quantile
2 cw wm
000178
Table 18 ThyrDoeicdaRteusruMlaslbeyNQouna-roPtfSirelrouEemdmpPulFoOcySeteD(iiNst=ori5nb4u)tion
SeMCrompmany
Ni Qviuese 4S-b13 ange MeanMeQduaine2S8O214 omge MeinQMuten3 i1SO49 Fame Mew MQeduaniSeOt) Range
TH 20 08 10 osd2 21 19 13 0mos2 30 2020 Le-Ms 16 1S 09 04-36
El si on 12 oIw 8T 2 79 16 62c -107 S082 13 6-02 87 a17 2a12 7e0s--10u9
Cm momm2on mmeewm mao m on B3 Mmeamne 7 0MB3 sm elsen neom 3 9Ei-eBe
Comer om
oe 27 28 64 20-34
24 26 04 18-32
24 23 05 12-26 25 04 20-32
m=.
+"4o5amTapbilcea11 ofr seerunmP(R<OS0g5i,Bcondfirtoi(oDnome es)mes valves
. 000179
Table 19
F3aMeCsoomlpa2n1y
||
HematoDleocgaytRureMsaloe NboynQPuroadurctotifoSineErlmupemloPyReOeS(NDi=s5ti4b)ution*
|
NiiQuiaels1giS=pt) a_ng_e _"_e_anQuMalic2in=1a orgs Vien QMueems(iS=D14) Wangs Mew QMueidtaen iS=O13 Wage
WT 6 a a mes 4 4 3 am a 6 3 aes 6 1 8w
NOB 153 ise 12 mooie 184 150 Li W2-mE M9 Iso 08 De-167 ISO ISI 05 10-160 RBC so so 03 47-55 $6 49 2% 45-181 45 48 03 43-53 SI 51 03 46=ss
WBC el $7 22 4-bi 60 61 lo 30-82 60 51 Ll 44-86 64 60 16 44-08
faPdueens 2 Ww mWw @B OmePw Tme"an WB mou6 M0 We SW 2m
Hes
SeegTioaDntfodsieentPRFO<S0u5,lBoenedirsiiDounne) es) cnvale
0c0150
Table 20 Decatur Male Non-Production Employee (N = 54) Urinalysis Results by Quartile of Serum PFOS Distribution*
Pa3gMe Cd9oomfp1a
Albumin
Blood
Sugar
QuNar(t%il)e 1
00
205)
000)
QuNar(t%il)e 2
00)
0
00)
QuNarti(l%e) 3
0
205)
0)
Numberof Employees: Q1 = 13; Q2=14; Q3 = 14; Q4= 13 *See Table 17 for serum PFOS quartile distribution
QuNar(t%il)e 4
1
0
0
000181
|
Tet
rauCosmpery
DeClciticulCFheemmaisPredRiecsitosn bayndQuNoani-lProodfsSceirounmEPmRpOlSoDyeiet(4t=o5n)
| Fa o m a om aal mee ae an anaThl amrei umow ok men ae ei enTeaa
WO eet om on emom om em om aeeam Pom wn ee
sm oss
Tr aa ex ew en-de wm ew on owen IWS 1B om ames wD 2m bs mm
Mo% wx oma 6 8 ow ms 4 0 6 mw ww 1 ws
Wms mew mss mows sn mews ms om as meme me om a meas
ewes 41 wo am ww ow am ne mem wn ow aw
omy3 0 5 wm 3 0 0 em + os em ns ns ew
ber Bow eer ore er oie wo or weer ww a eo
Cd Wm 6 mew om mu mae wm 8 wen om a mow
ws wu we @ = on en ew ww ss 0 wn
To wwe wm wm mw am ow wm awe a ww wm
I
wr wwe em wom
x om on om we ow 5s ew
st mow x ona wows ww ow ws ew ow ns uw
ar mw on em won 0 wx om on on ea nw 6 ee
mabussa 40 06 03 030s 0s 06 0 we G6 0s eee 0s 6s 0 oar
wF om mo 4 sm E oowmoomo 3 ww won en on ns ow
Comore 0 ot 0x een or oro oi ww oe 0 eo ow
Ge mm 5 nem ww so mw ww 1 ow nw 5 mm
NbrfF oesby ton gry le {Me pct lc.1%, ron Decafof ntbe ee
II Cawina ioa n eonomeb5iSmW ict RiemiEtSoSk Eiteimei |ers2
|
Tabe22
PCaeosmtapl
|
`DecaTthuyrrFoeimdaRlseuPlrosdubcytiQounaarntdiNloofen-SPerroudmucPtiRoOnSEDmipsltotyie(oNen= 48)
E pote 1r 1-1 TI Quea quae3-a 1 Queicau=1y CT
Tw mow noma 2 om wb wesw am 12 wes 1m es bea
TW as esos 9 ww sem: sr m0 1 wens a mM 23 sew FT 10 W000 0.3L 10 e103 to 10 on wel Go 10 or asi Bom om mem mom wen me aw % dew @ 2 2 wwe mR ow 3 ww ow om 3 mw wm x 4 mw am om 4 wn mw wes was 2s 2s 0s Gea 1 2 00 lew mw 0 aes
NTosigsIificay difrotF(C<S05,Bonfetroon (Dnun) et)mes vl
000183
Table23 DecaHteumratFoelmoaglyeRPersuoldtusctbioyn QuaanrdtNono-fPSroedruucmtPioRnOESmDpilsotyiebeu(tNion=48)
Fie Muedtaen 1-SD1 Tmge Www 3 wes WO m6 17 12 99-4 RIC 43 43 03 Meds WC 67 63 20 42-07
Paes AC 0 6 0
Win QMueidtae20S4D-2) Wage Wen QMuedaen i5=01 Fame 0s 2 es 1 %ew D3 03 06 Ras 29 18 05 BONS 43 43 03 27-48 44 43 03 39-50 66 6S 19 43-104 59 62 17 20-84
Wm Nee WS@ WW 26 MW Wem
5iccnnTabble21y noryselrceoRnOnS.<qu5a5r.tDiBcirdriatesioD(nuuecetffebhee mmnmoffhe =gstce hiinn ccmtt fffl 7<<555.DBrroonsDDeoen)foosbeernnooffbhee3g ltele
Pag0eCsozmapran2y1
Wem QMueidtae4iS=b1) Farge 0 0 4 ues NA D4 14 3-162 43 44 08 39-50 76 75 19 42-104 m3 5 9w
000184
Table 24. Decatur Female Production and Non-Production Employee (N = 48)
Urinalysis Resuls by Quartile of Serum PFOS Distribution
Pa2gMe CS3oomfpa1n2
Albumin Blood
Sugar
Quartile 1 N(%) 00 207
00)
Quartile 2 N (%) 0) 00
00)
Quartile 3 N(%) 207 305)
0
Quartile 4 N (%) 0 00)
00)
Number of Employees: Q1 = 12; Q2= 12; Q3 = 12; Q4 = 12 *See Table 21 for serum PFOS quartile distribution
000185
Table 25
PreStof120
`Who HaNduAmbboevreofRePfaerrteinccipeanRtasn(gPeerVcaelnuteisnfPoarrcHnehpeastiisc)CSltinriactailfiCehdebmyisAtnrtywTeersptosrbDyeQcuaatrutirlEempoflSoeyreuemPopPuFlOaStiDoinsstebution
san EAt coe Miia! 0 Om Om 0m Md om 0m 00 G0 Km' 00 0 00 se
ase r a 10) 00 om om be 0G Sm 10 0m Gm om Se
ee a e weeoaree
10) 0 0@ Sm Gm 1m 0B Sm Ge 0@ om 0m
10) 10 30 Gn 10H 30) 10 G0 0 oe cm
a mati re at = dm sm) 40h sen 0 05 Om 16 ca im om en
rat 10 16 20 10 Niel 0@ 0G 0B Gm
Gm 10 om eB SO GR 0@ 00 0m 0m IB 10 0 0m
J
I
bon
S$c5Eh5TuTtaieklAeeidfono uePvnoFP,ROOSSAgSnaT.tiAeeLTd,GuOTii,snTo and DicBit
5$555TTTilolleee 1310aresntPPPOEOSSSpgqullaetee hbitonnn
SekTe 1fo sr POSql dibaion
4h O 30 60) Sm 3G) 60 IG
TD 1 Tm oh, l 300 200 1
000156
Table26 Flsorochemical ADnetmwoegrrpaapnhdicDeantdaCrlinsicalCPhreodmuicstiiroynReasnudlNtosr.byPQrouduactlionofS(eN=r4um2P1R)OSDisibuion
Pcasosmspoarn1y1
fone Tos om om on oem ow ow an coco dor as an om oom la om up ower dor a eo om sam LOM Le om oN-se a Ww ox bm me a w wa mi ar mi 0 mes me Ms 40 mem owed 0 ws sm maw Coty 0 + we so wm oa F Coed We. 4 wS m me an 6 mow ww mw em 0 8 uw mm eta wm mem ws em mes ao GW mew @ ww we wr ow mw wm mm om aw wx wm 1 mes mw 6 wee wr ow mow me mm ou we Time 100 G9 0 asa os as 03 meas ww m1 am mon 4 am Comme 12 0 es ones 1 me ea FR
Ge Len ax Le G0 Lp
Im om @65 mW) 4S 6 eq 6 om
eS omois 20% 26 10) 10mm one 20 20 10 om-nw oees a am ison ma 5 mw nase ma ue 45 mass ws wo a oe 6 0 Ww 00
ms ew wow mo a 4 mow
ow & Bue a 8
mew
wm mo omem msm wom
@ 9 ow Wwe Ww @ was
wns em 3 ww
ww 7 1m mM 3 we
mom ou ew ww
as on on meio of 07 03 eam
I
CE
mw samme 3 en
1 WM esse Lip 03 esis
"Table26 continued)
3M Company preseotizt
"Numb
of
maecmploQeueistbey oan, proiction egyQusnidtqea?ri (peice fn Ti NaaTRn Neon
penbesis) Todi
QuiNts Ps
|
oy
=
`
ene 7
=
"
sn
ra TRG we mee hide wen 0
Poles QuiNeatePueckn
2
@
`
wes ee
| iteemnnipgceftyyciffsooteaty<<0533..DDBelrstraron(D(Daua es iimthheccconnofoff e3Z1ucl'e ee py lls P< 3 eco) 8 oi co 4 re
000188
Table27
tra3pe0e4CSo7m0p0a1n2y1
|
`Antwerpa"nTdhDyercoaitduRresMualtesPbryodQuucatrtiiolneaonfdSeNrounm-PPrRoOduScDiiosntErmibpultoioynee(N =421)
Vics Qpiuedion SO10 ange WemMeQudianne?(4Sb=105).fame WenQMuogean 04S1O06) Fame Wem QuMiettien403SD109 Fame
TS 20 19 12 e@-s3 31 20 66 03-63 (20 17 20 02-88 25 19 28 0s-2us
Ed B30 BS 0124 S0o9--1n5s 8L2 Lme 0M14 4026-l240 8M3L 8L2I 0A2S 3043--l96 8L4I 812 2M02 4078--i16d
Feet 11 1 n a mn see
ms mm
sem
me a
ese
mm
mo
gm
mR Ww 3 mew mB 3 ua WW om 3 we
om 3 mea
mm 27 27 0s 12-42 26 25 04 12-40 26 26 05 10-41 26 26 04 16-36
eS
"eSteeeeemTnublee2e6ffytotrsyyedlamoriFotOtnSPP<<<di005s5,.,iBhueirttoroenronss((nDeoeee1tscfhomem ehhei memcafftBhee3=1Gqrualect'e
en lcntyict < 5Rte ue 1a oh mf he * are
000159
--
acsoimpaans
||
Fluorochemical,ADvetmwoegrraspnhdiDceancdtClFineicaaltChPemriistoynResnuldtsNboyQuParrduiclioofnS0e4r2u9m7P)ROS Disbution
Te
om
om omesow m ont v on ae m sl ean
ow an
as
=
mma
t 80 00 n aw aa nos
B mr am om oo eseT n ond on an gman owes aa onsm
en anY ew ew
awei Emae Elmm9 oumemms Bwewm 7 m5-m9 ds EbIe Gw2e5-5n8 w"Rosms6 w0e-2s
cov #8 4 em
Fo 3
ew
2
0
7.
LL em # o
b
oa
--
0d
we et a mw mem wm
wom wm ow
ene 0m mow ww on
ea wen
#0 om mm a
en mew
oti nm % ma ww 4 E mm ww E 9 am Ww wm awe
ew me mw wr ww 1 am
we wu mm 4
ma sa
ws won
6 6
ww eww mw wom
aw en
oe ws we ww 1 ee mows wm mow 7 ow
I J
J
ee ow ou Mew ow
wn
sons 8
I I LE ER
non em o nn eam
00190
|1|
Ta28Colntee)
| "Number femal cmpolopter sbbc eccocT eransd gai (centinpea es)ues
Tha outs
ous 3MCompany
--
.
.
rw
.
."
a:
wwawe
o mmfrsettstfeoe<20 t re et n 1t ofmoneeereemme t re
000191
Tule20
PaIgMeC0o0m1pa1n2y1
|
Antwerpan"dThyDreociadtuRresFuelmtaslebyPrQoudaurcttiileonofanSderNounm-PPFroOdSucDtiisotnriEbmutpiloonye*e (N =97)
|
Que|.
- "WomWaloQnuatS2eb ange Wen WQotaun e$0 Romy
SH a1 22 12 ameas 22 20 1s OMe 35 2 cl 07-65
E wr 02 20 sens 98 98 3 46-3 99 93 23 SEs
OE I n Ws a0 wm sem a ms
CT meds mS sem
me 4 we 3 om 6 mew mw wm 3 pox
m rmow a w15 0w s aw io 2 30 28 3 A7-a4 27 11 05 1
|
+eNoSseiegTnaibfliec2a8nftoyrdsifefreuremntPF(PO<S
05, Bonferroni (Dunn) quartiledistibution
test)
mean
values
Wem VeQduainteS4D. Msg 23 22 10 10oS2 91 B12 Si
01-12
mmm we
womo4wem a a 0 M30
i
000192
en
Fi
| Wh 1 Above ReteRaamtb VtPtcBioppns (CcheteiCPenetns)byEbmypQluan FpoifSlestinPROSDihtion
son _-- a F ; a eaw e
ee
Mak Boyes
event --r--n ow wn om
tm 10 om wm
'
.
wm ke om om ow mw 1m
ew mw
E rae-- R C -- T e ------
J 000193
Tae 31
|
|
Mul{otrivAarmniadeblrOe lRneegdrDePsaosttieounntMMoEdoxelpleloaEnfamCtpholorolyyesVetaeerirPaoablil*ceibspyanPtFsO,S
So Metical Surveiance Program
eee
Inereept
pros Production Job(yess) AntwerpDecatur ee a
Clgaeesdny Drinklday Years Worked
ROTO
som
[2 -o010 ~0s 0006 oon 00007 00s 000
sec
oust
oon oom os oo oo oon oor2 oon
pwwe
001
o " a an " ao 15
|
R=08
!
A"GNRu=a0l6og
racCiooptya
pwi
> <ot <on <a
o <ot <n o <a
000194
Table 32 MulivariasnbdlOetRheegrrePostseinotniaMloEdxepllaonfCahtoorlyesVtareirsobllebsy PFOA
forAntwer"2p0a00ndMedDieccaatluSruMravelielElamnpcleoPyreoegPraarmticipants,
| woo Parameter
se
pualue
Inereept
5069
0080
001
|
PFOA
001s
0008
0
Production Jb (yes/no)
0012
0024
Le
Aniwer/Decatur
-0032
002s
2
Age
0007
0002
001
BMI
0001
0002
"
Cigaretesiday
00006
0001
2
Drinksiday
| Ves Worked
003
oot
oom
oon
005
a
.-
A"NatRura=l.l0o6g
P3aMsaC3oomlpa1n2y1
Partial R <0 <0 <0 0 <0 <0 2
<n
000195.
y
Table 33
MuliviblenRgoresisonPoMtoednetl oEfxChpollnessotreyroVlarbiyabPlFesOS and PFOA
{oe Amer53y00ndMDeteicntSMuolelEampiPyroegPaamricpans,
Pwr
SE
palue.
nent
S066
ost
<n
pros
ois
000
1
Pro
ous
ooo
P
Protation 0 ese) ons
oo
"
AniwepDccae
om
ons
ae
07
ou
01
a
oot
ao
o
--
oor
oor
Py
Drnktay
oms
oor2
aot
Yours Worked
oom
oor
is
Ara--
Paral R?
. <a <a <a <a os <n <a
o ot
Nag R=08
]
AdjR'= 06
000196
F5aMeCSomapraanty
|
Table 34
Maliva"rainadlOethReergrPeostesnitoinalMoExdpellaonfatCohroylVsatrriaobllebsyTOF
for An3t00sw0nMdeeDdeicrcaatlpuSruMravleielElmanpcleoryoegerPaamrticipants,
Parameter
s8
Inecept
5065
00st
||
Tor
oois
0006
Production Job (esio)
-0018
+ oon
AntwerDecaiur
-0034
00s
Are.
0007
[3
BMI
0001
oon
Cigreticsiday
00006
* oot
Drinks
00
oon
Years Worked.
-o00
oo
owe?
|
RAG0RI8=07
"Naural log
|
pia
Pari B
<o001
.
<ot
as
<0
as
<ot
oot
os
@
<o
El
<or
0s
o
6
<0
000197
m-- Me ome,
RAlG=R3I3=32
ms
PR
o m m Se w m wma.nn o a;. Parameter
SE
value
Partial R*
000198
Tie36 foMrolAinnvaderarOblaeendRePDgercteastseuironMEMaxoipdaeEnlmspooflroIyyDVeaeLriPaabbryliPecsFpaOnAs,
2000 Medical Suilnce Progam
eeeemer eee VOR
Inert
as
|
Proa
~oo1
Production Job(yesno)
os
AntwerpDecaur
-00
ae
oo
Ba
~o019
Cigartestiay
~0004
Drinksldsy
oom
Years Worked
-0001
se
pele
00%
<n
0009
o
002
El
oos
5
0002
oon
<oon
oon
aos
oom
<0
oon
4
FSaMeaCromaptaanty
pei
on <or
<0 o on % <or
|
R'=34
A"dNjaRura=l o3g2
:
000199
_ Inereept PROS PFOA Production Job (yesino) Anmwerpecatur TM BMI Cigaretestday
Drinklday Years Worked eRA=G3R4= 2 "Natural log
Table 37 MulivarisbalnedRheegrressPiooennMtoaldeElxoplfaHnDatLorybVyarPiFabOlSesand PFOA
for Antwe2r0p0a0nMdeDdeiccaatluSruMrvaeliellEamnpcleoPyreoegrPaarmticipants,
Parameter
se.
pulse
aan
00%
<0001
0006
oor2
-000
0010
o
002s
oan
36
003
0028
EY
0001
002
50
-0019
0003
<0
-0004
0001
0004
oon
ooi4
<.0001
-0001
0002
49
P3etCaomrpa3n1y
Paral B
o 0 <ot " <0 on o 0% <0
000200
nreent Tor Production Job(yesne) AntwerpDecaur Ae Bt Cigaretesiday Drinksldny Yeas Worked om
Wa
A"Nat=al l1o)g
Table 38 MaliavnadrOitslheeRPeogtrenetsisailonExMpoldaenaltoofryHVDarLibbiyeTs OF for Antwe0rp0snMdedDieccaatluSruMrvoeliellEamnpceloPyreoegPaamrticipants,
[rr
se
pualue
wm
00%
<0
-0010
0007
u
[2
oon
"
-00s0
os
os
oon
ooo
#5
009
0003
<o00n
-000
ooo
0004
0084
oon
<0
~00009
0002
58
Fadel it
Paral B
0 <ot 15 <0 o o 0 <or
000201
Inercept
PROS. Production Job (yes/no)
AnwerpDecatur Age Mi Cigaretelday Denkslday Years Worked
wot? RAg=G2R8= 21 "Natur log
Table 39 MulivarainahdeOtRheegrrePsostieonntiMalodEexplloafnaTtroirgylyVcaerriisdbelsesby PROS
for Antwe2r0p0a0nMdeDedciactauSruMrvaeiclElmanpcleoPyreoegPraartmicipants,
Parameter
Se
pale
2768
02
<0001
0066
0026
o
oo
006s
n
ost
0068
oor
000s
09
005s
0007
<0001
0008
0003
0
oom
0034
-0007
0004
0
:
3PaMgeC1o0m0p1a1n2y1
Panis) 0 <0 a0 10 2 <0 <0
000202
Inereept
POA Praducion Job (yesoe) AntverDecsur Age war
Cipueesiny
Drinkaldey Years Worked Je RA=R2= 21 "Natl fog
Table 0 MolivasiaubndleOtRehgerrePsostieonntiMaoldEexlpolafnTatroirlyycVearrdieasl*esbyPFOA
for Antwe2rp0anMdeDdeicctauSruMealielEamnpcloPyreoegaPmar.ticipants,
pum
ise
pie
270
om
<o001
0066
oo
wo
~0004
0066
55
om
oon
oon
000s
os
005s
0007
<o00t
000
oon
ons
oo
oom
1s
0007
0004
a
enmopn
Paria 05 <or os o 0 <or ws
00203
Intercept
PROS. PFOA Production Job (yes/no) AntwerDecatur Are MI Cigartcsay. Drnkslday Years Worked ee... RAG=E = 21 *Nauwnl log
Table 1 `Mulivarisble RaengdrehsesironPMootednetliolfETxrpillayncateorrdyeVsaribayblPeFsOS and PFOA
for Antwe"r2p00u0nMdeDdeiccaatluSruMrvleiellEanmcpeloPyreoegrPaamrticipants,
tamer
SE
pualue
2m
04
<.0001
0037
oom
2
0053
oo
2
-0021
0067
26
0109
oom0
n
oot
000s
01
008s
0007
<o001
0008
0003
0
0030
oom
as
-0007
ooo
0
PuetrCoomtpa2n1y
Paria R* 0 o <0 0 " a0 o <0 <0
00020%
. Inert
Tor Production Job yes) AwenDecaor
ne BML
Ciguetestiny Drinkldsy Years Worked owloded Ag=R2=21 "Nawal log
Table 2 Ma{loirvAanrutnswdebOrlntReserngdrPeDosteescniatotinaulMroMEdxleplelaoEnfamTtporrlyioVgyayPseaeircsiibpdyaenTssO,*F
2000 Medical Survilnce Program
Parameter
se
phe
2736
om
<o00t
00%
oon?
009
-oor
0067
&
ous
oon
10
oon
000s
ws
005s
oon
<o001
0008
000
wo
oon
oom
x
-0007
0004
o
~~
a swcom
Pus R* <ot os o 10 o <ot <ot
000205
|
a
[I
Pros Produion Job yes) AntwepDecsuc he a Cipretestiny Dik Yours Worked
Cec Tiet nes
|
AG =16
"Haunt log
"Table 43
liv{oie AanReegrnrsarindotnDeeeicltlMsoflpAellaEinnrpeyPoVhaoPsrrpathihaitaensb,y FOS 50 Met Survie Pog
Parameter
SE
pvalue
sms
os
<r
0013
oon
2
ome
oon
2
ou
oo
<a
aos
ou
ES
"oot
oot
2
om
oat
0
"oo
oote
1
"002
oo
a
oon
oo
0s
aeons
.Partial R" <a n pr <n <a <a <a
000206
Table44 MalivasisbeaRnedgOrtehsesiroPnotMeontdieall oEfxpAllanaaitonryPVhaorsipahbaletsase byPFOA
for Antwe2r0p0a0nMdeDdeiccaatuSrurMvaeilllEamnpceloPyreoegrPaamticpanis,
Pane
SB
pale
Inereeps
ant
ozs
<oo01
ProA
0001
0010
Production ob(yesno)
0047
oo
Las
AniwerpDecatur
01st
[=
<o001
| Ae
00s
ou
0
BMI
-00m
0004
2
Cigaretesiday
[
0001
as
Drinksday
002s
[2
a
Years Worked
-0001
oo
EY
Tighyerdest
[
oo
000s
Rests "ANGawIal= lo1g0
FMsCToSmopla2n1y
Puri 0 <0 10
<a
<or <0 <0 <or
000207
Inercept PROS PFOA Production ob (yesho) AnwerpDecator 3 MI Cigaretesiday Drnkslday Years Worked Trglyeridess -_ RAG1R8=.16 *Nawnl log
Table 45 Mulivarisble RegrensdsiOotnhMerodPeoltenotfiaAllkBaxlpilneanPthoorsyphVtaarisaeb*lebsy PROS and PFOA
for Antwe2r0p0a0nMdeDdeiccaatuSruMrvaeliellEamnpcleoPyreoegrPaarmticipants,
[a
SE
pale
a4
0128
<1
ots
[x
2
-0005
oor2
85
000
[=
2
0153
oon
<1
00007
0002
a
-0004
ont
25
0002
ooo
an
004
oor?
as
-0002
0002
"2
008s
oot
os
.
P3eMtCaomlpainny
Paria B* " 0 <0 <0 10 <0 <0 <0 <0 <0
000208
Table 46 Mulivarisbl"enRdegOrerssiPoonteMnotdieallEoxfplAalnkaaltionreyPVhaorsipahblaetsase? by TOF
for Antwe"r2p00a0nMdeDdeiccaatluSruMrvaeliellEamnpceloPyreoegrPaamrticipants,
P5eM Caomtpany
AlkPhos
_
Parameter
se
pulse
[NN
Intercept
am
0128
<0001
-
Tor
0006
0008
La
0
Production Job (yesho)
0037
oom
2
<0
AmwerpDecatur
0147
oon
<0001
a0
Are
00008
ooo
n
<0
BMI
-0004
0004
25
<0
Cigaretesiay
0002
oor
a8
<0
Drinksday
-0024
0016
I
<0
Years Worked
-0002
oo
as
<0
Triglyeerides
[x
[
0006.
2
0
RAG=RI18= 16 Natural log
000209
||
]]]
]
Co
em
ros
]
riguo J--
p-
Cm
--"
Coa
en
Toon
Mian Ri=25
AdjR'=23
Tew r opeoree eseonof, GeTenbyFOS
- Pumeler
oSEn _ pcuaolume
oon
oom
-0m2
ons
*
os oss
ons
ont
<om 5
one ows
or ons
x
om or
oi oo
own "
om
ons
coon
us--e_r--
P .anial B " w o a " = on =
000210
|
Table 48
MulivaanrdisObtlheerRePogtreenstsiiaolnEMxopldaenlatoofrGyGVTar*iabbylePsFOA for Antwe2r0p0a0nMdeDdeiccaatuSrurMvaelielElmanpcleoPyreoegrPaarmticipants,
|
_
Parameter
Intercept
L245
PFOA
0032
|
Production ob(yes)
-000
AnwerpDecatur
os
Age
00009
BMI
0006
Cigaetesday
0003
Drinksday
0116
Years Worked
0003
Trglycerides
0289
-_
|
RA==25 21
Natu log.
se 0238 oot 0060 0065 0004 or 0003 oon 0004 004s
pualoe <0001 010 Ca 0003
#" as 28
0002 40 <1
P5MeCoomrpianay
Paria RY . o <0 0 o 2 or 0 <0 0
000211
Table 49
MulivaisbalnedROetheesiPootnentMioadleElxpolfaGnaGtoTrybVyaiPsFbOlSesand PFOA forAnte300n0dMeDdieacltSuMrvleeillEamnpcleoPyreosgrPaamricipats,
PaweCsomop
_
Paameter
SE
palue
Panial R
Intercept
1206
oz
<oon
.
pros
oon
oo
-
Pron
oo
oo
x
o
Production ob yesho) -0026
0062
a
<o01
|
AnwerDecatur
on
006s
ES
"
a
00009
00s
on
EY
0006
0007
3
@
Cigseesiny
000
0003
zn
o
Dinky
ous
oon
on
on
|
Years Worked
0003
0004
45
<on
Tilyeridest
0288
001s
<o001
os
--
|
R= 25
A"NiatuRra=l 2lo3g
000212
Table 0 MlivanadriOathleerRPoteentgialrExeMpoldsaenalstooifryGoVGaTnr*ibsiyeTsOF. for Antwe2rp00snMdeDdeiccatlurSuMrvaeiillEamnpceloPyreoegrPaamrticipants,
_
rumor
se
pualie
nereet
1266
os
<n
Tor
009
ooi6
06
Praducion Job (ese)
00s
061
4
Antwerp Decatur
0235
0064
003
I
[I
0004
=
Bt
0006
0007
Cigartesday
0003
000s
=
Drinklday
outs
ost
002
ears Worked
0003
[x
"
Tighyeerdest
oss
00s
<o001
|
Kags
:
MI: 31
Natur log
PMaesCiuopla3r1y
Parial B on <or o o o 0 <ot o
000213
|
Table 51 MalainvdarOtahbelrRPeogtreenstsiailonExMplanoatoofrAydSVTaribeabylePslROS for Antwe2r0p00snMdeDdeiccaatluSruMvalielEncleoPryogPaamicipats,
;
Parameter
se
prac
Intercept
ams
om
<oo0t
pros
003
0013
3
Production Job ese) -o0n
oom
Lo
AvtwerpDecsur
ou
003s
on
ae
0003
0002
EY
Bi
[3
000
Ee)
[r--
-0003
oo
o
Drinalday
o0s2
0017
0
Years Worked
~o004
0002
05
Tglycerdes
00s
oms
o
,--
RAGeREg= 07 "Naural og
rMeCsamopu3ln0y
[ST <or <or os <n <or <0 on o
000214
(
ER epiyn `Table52
Parameter
SE
pvalue
ievennsi awar0 wnoe --
"oe
pwon ppoo" x-
rSonn ownn -an -.
rJe oome ouae -
eSMeta
sm
PartiaRl
wno =ww hs".
000215
|
_--
|
MallifovraArniistbnwlederORpteahgenrredPsosDtieeocnnattiMauolrdMeElxapollfAaEnSamTtpo*rlyobVyyarPiPFaarbOtiSiecsinpadntPs,FOA.
2000 Medical Sureilance rogram
|
-- ee
emer
SB
puke
erent
ams
om
<oo0t
|
pros
0006
00s
@
| PrroA------ 200313
aooor
2;
|
Antwerp/Decatur
0104
"oo
004
|
Age
0.003
0.002
23
Bi
0002
0004
0
Cigaretestiay
-0003
oot
o
Drinkslday
0052
oon?
ons
Years Worked
-000s
oon
o
| geste
oos2
ams
o
UARe= 07
.
Heal log
r3eMsCoomrpta
Paia
. <n
w<ot
2
<o1
<or <or o o
<a
000216
|
Table 34
MultainvadrOitabhleer PRoetgernetsisailoEnxMplaonatodofryAeSVaTlr*isbbiyeTsOF for An20t0a0nMwdeDdeicecaatlurSruMravpeliellEamnpceloPyreoegrPaarmticipants,
Intercept TOF
Production ob (yes/no) AntwerpDecatur Age BM Cigaretteslday Drnkslday Years Warked Triglycerides
bummer ams oon 0031 0106
[3 0002 -0003 0052 0004 003
SE
puilue
om
<.0001
0009
a1
0034
EY
0036
0
002
2%
0004
st
[
0
oor7
0
0002
of
00s
0
RAG=R= 07 "Naural log
:
Paagne C8o5mopfa1n2y1
Panial R*
o <or 2 <0 <r <0 2 on <0
000217
Table 55 MuliavnadriObtlheerRPeogtreenstsiailonExMpoldaenlstoofryALVaTr*iabbylePsROS for Antwe"r2p00a0nMdeDdeiccaaltuSrurMveaillEamnpceloPyreosgrPaamrticipants,
Paa0 Cgoamerpa1n2y1
S--
|
Inercept
Pumeer SE
144
oles
|
pros
oo
ooig
Production ob(yesio)
oor?
0
AntwerpDecatur
om
002
Age
0002
0003
BMI
002s
004
Cigareteslday
-0007
0002
Drnkslday
0006
0024
Years Worked
-000
0002
Trglyeridest
0189
oon
AR=I2= 25 "Natral log.
puke Paiul'
<.0001
-
2
on
<0
<0001
%
0
<0
<.0001
5
0003
ol
2
<0
10
<n
<0001
05
:
000218
| rcornept ssi amv a Comtr
ros
onR a oSl AVa
mew
poe
o16s1
Iost
r-e
00m
won
a
ans am
wa oon
<a u
on ann
won oun
om an
arimor
me w.o on a wo.
Yom SR
am oro
on oz
<a
wo
cS
]
Adj R= 25
000219
{
aes? Mlle"nd ROepgerrePsoonntMoadeElxopflAaLntTsbVyaPrRaOlSs1nd PFOA for AcS000ndMeDdieacltSMuilemEimigrgaPmrins,
_
J Pros Pron
Puomeer
=
pale
191
os
<n
oot
ois
2
oom
om
Cas
pa an oon cm Production Job (yes/no)
0013
0043
76
Anwerpecaue
ors
oo
<oo0n
hee
om
ow
PF
wa
ons
oot
<omt
Cipeeesiny
"0001
oo
oon
Drnstny
ome
oo
5
Years Worked
Er
om
a
i
R= 5
Nios
Paestaatl
Paral
. on <a
<.01
o <a <a <or <a
000220
Tale 58 Maliavnadritslblee RPeotgernetsisailoBnpMloadnetloorfyAVLaTr*ibbiyeTsOR for Antwe2r0p0n0dMeDdeiccaatluSrurMvaeiellEamnpceloPyreoegrPaamints,
eswsCurps
vwwmeer
se
pate
Paria
Inereen
1965
0193
<o001
-
Tor
om
0013
os
Production Job(yesh) ~00s4
0050
Ed
<or
AntweDecaur
0296
00st
<0
5
I
-0003
0004
38
<on
wr
oon
000s
@
o
Cipmnesiny
-000
0002
ons
o
Drinkslday
oo
oas
@
<ot
Yeas Worked
-0002
000
"
<or
| a Tgleeridest 01% oot <o001 os
|
AR"Naw G=RE3= 31
:
ns
:
000221
Table $9 Malivarinbdl tRheeesPiootnenMotdeElxpolfaTnottoarlyBVialriiraubbliens byPFOS
for Antwe5r0p0s0nMdeDdeicaaltuSruMravetielaEnmcpeloryoegerPaamricipants,
PMssCoamspatyt
_Panmewr
SE
pvalue
Partial R
|
Intercept
0209
0.145
<.0001
-
pros
~oon7
oots
as
Production ob(yesno) ~o006s
00%
Lo.
o
AnverpDecatur
"022
00%
<oo01
1
I
oon
0003
58
<n
En
-o0s
000s
a
<on
Cigaetesiny
-000s
0002
<1
Drinkslday
oas
00
<or
Years Worked
0002
oon
<or
| Trgyeerids
~oo1s
oo
51
<r
--
R'=29
A"dNgiaRn'=l2o1g
000222
|
CE ie peo`MTablfe60Ta Bi HOA
Parameter
SE
pave
ParaBl
enon Ls ASxge .oo-0o002 mo0=0o03 mo43oLo<0
oom kisR'=29
AiR =2 000223
Inercept PROS. Proa
Production Job(yes) AnmwerpDecator Age BMI Cigaretesiay Drinkslday Years Worked Trglyerides
RA=GR = 21 Nawal log
Table 61 `Mulivarible R`eagnrdeOstshieorn PMootdenetliaolfTEoxtpallanBatioiruybiVanriabbylePsFOS and PFOA
for Antwe"r2p00a0nMdeDdeiccaajluSruMravleillEamnpceloPyreoegrPaarmticipants,
Parmer
se
pyalue
0209
014
<o001
-0018
0016
zn
0002
oor3
36
-0070
0037
6
0264
0039
<0001
oom
0003
5
-0005
0004
2
-0008
0002
<0001
0005
0002
a
00002
0002
95
-0016
00
36
P3aMgCeomrpainaly
Pani B
o o 16 <0 <0 % <0 <0 <0
000224
-- Intercept TOF Production Job (yes/no) AntwerpDecsiur Age
BMI Cigaretes/day Drinks/day Years Worked. Triglycerides RAG=R2I9= 27 Noto log.
Table 62 Multivari`aabnldeOtRehgerresPostieonntiMaoldEexlpolafnaTtotoary BVialriiaubbliensbyTOF
for Anuwe2r0p00anMdeDdeiccaatluSruMrvaeliellEamnpceloPyreoegrPaarmticipants,
Pum
SE
palue
0210
0.144
<.0001
-oo11
0009
2s
-0064
0037
0
-0257
0039
<.0001
0001
0.003
62
-0005
0004
19
-0008
0002
<.0001
0005
0019
TM
0.00007
0002
98
-0014
00x
)
PaaMgCeo3mopfa1n2y1
Partial B
06 o 16 <o <0 % <o1 <o1 <0
000225
Co erent
Pros Production JobGeshe) AnwerDecaar I a [er---- Driksiy Years Worked Tigers to aAdRyI= 05 Nowra iog
Tale
.
MulinvadritbhlerRPeogtreenstsiailonBxMpoldaesltoofrTySVHariabhycPsROS
for AntwSeronnddDicatrSMuvaeeiaEnmcpeloPyreoegPaamr.icipans,
vewee SE
pike
0s
om
1
oois
oom
ss
oi
* oon
1
oi
0086
000s
00s
x
~000s
oo
56
000s
oon
an
00s
oon
nn
~0008
000s
5
0204
0061
on
Peter
Pari . <a <0 @ <a <a <a <on <0
000226
--
Pron Producion ob yesho) AnwerpDecatur Awe wat
Cigeestay Dik Years Worked Tigleerdest
Table64 MoliavnadriObtlhceRPeogteenstiiaolnEMxpoldaesltoofrTy IVa*isbblyePsFOA forAntwe3r0p0s0nMdeDdeicaaltuSruMarlveeEmipllloyraeonegrPcaaremicipants,
var
SE
"0s
om
oo
0027
0100
0083
om
008s
000
0006
-o0s
0009
~000s
0003
00s6
0002
-0008
000s
0201
0002
pale
10
5 = os 5 56 0 8 an oon
Ri=07
A"dNiaRwa'l= l0o5g
MCompany
PR
n <or <o1 <or <on <0 <or <0
000227
| ae |
Table 65
|
Mol{iovr aAan"btunewd rOReatgenrsedsPsDiooencMtaodteElxepolfEaTnmaSptHoirpyebVyaPrPFaiOreSiscsinpdnPs,FOA
|
300 Metin Survie Program
net
Parameter
~0s3
pros
oon
Pron
ois
[--
ome
AmyerpDecauc
om
ae
oes
mat
0005
Cipretesiy
0005
Dinky
ooss
Yours Worked
0008
Tigheridest ammo eomee
SE
om
om om 00s oom
oms om
000s oon ous
een oos
Ria a
fchoerid
:
10 pvalue
.Partial R?
ss
<a
a
<a
a
<a
os
po
=
<a
sn
<a
Fa
<a
a
<a
wn
<0
0----iemeeet
000228
Table66
MultainvadrOitabhleer RPeotgernetsisailoEnxMploadnealtoofryTSVaHriabbyleTs OF for Antwe2r0p0a0nMdeDdeiccaatluSrurMvaeliellEamnpceloPyreoegrPaarmticipants, |
Parameter
se
palue.
Intercept
0539
037
10
Tor
001s
0021
o
Production Job (yes/no)
0097
0.084
2s
AntwerpDecatur
an
0088
05
Age
0006
0.006
Ed
BMI
-0005
0.009
51
Cigaretiesday
0005
+ 0003
n
Drinks/day
0056
00s
a8
Years Worked
-0008
0005
a2
Triglycerides
0201
0062
01
R=01 AGR'=
05
*Natural log.
Pa3gMe9C7o0m1pa1n2y1
Partial R? 2 <o o <o <o <0 <0 <0 2
000229
|
PaaMsCtoempra2n1y
Table 67
Mul"iavndarOibtle RPoetgernetsisalioEnxpMloadnealtoorfyTV4a*ribayblPeRsOS for Antwe"r2p00a0nMdeDdeiccaatluSruMrvaeliellEamnpceloPyreoegrPaamrticipants,
_ Pwmeer
SE
pane
Pais]
Inercept Pros
2263
00%
<n
-
-0003
0009
7
<0
Production Jb (yes/no)
-000
oom
on
<0
pr --
oon
0024
ot
<0
Ase
000
000
0
<0
BMI
0001
0003
%
<0
Cigaretesilay
00009
00009
=
<0
Drnkslday
0024
oor2
0
<n
Years Worked
oor
0001
3s
<0
a -- Trglyeer-- ides--ema-- ete r-- e --- o018 ----oo-- r? ----2---- ene-- <e 0 -- --
ARG=R = 01
3
*Natun log
000230
|
Table 68
MaliavnadrOitbhleer PReogernetsisailoEnxMploadnealtoofrTy4V*arbiyblPesFOA for Antwe"r2p00a0nMdeDdeicaaltuSrurMvaeilllEamnpceloPyreoegrPaamrticipants,
Parameter
se
pale
Intercept
2263
0050
<o001
Pro"
00003
0007
9
|
Production ob (yesino)
-0005
oon
AnverpfDecatur
oot0
0024
Age
000
oa
9
BM
oot
"oo
"
Cigaretesiday
oor
00009
2
Drinkslday
002
oot
0
Years Worked
oor
0001
3
Tighycerides
-0019
oor?
2
RAR== 01 "Naural log
Pt
Partial <0 <on <0 <0 <0 <0 <0 <0 <0
000231
eens Pros Pron Produ Ib Ges) AtwepDecar ne ot Cipmetedtay Dinky Yours Worked
Trglyeeridess
rR =L.i
Nios
aes Mui(ovraAranieiORneagnsrdePDseictoanteMroMxidplelofnBTop4rl*aybyeVePaRPOaaSlrsidaP,FOA
pi
Parameter
SE
p.value.
20
amo
<a
"om
oon
Eh
oor
oes
16
000s
om
-
oot
oo
"
oan
om
oor
TM
os
ous
00009
Er
oon
o
oor
oor
1
-o0i8
oor
2
racotmipoan
Partial R*
pr pr pr pr or cor <a pr <a
<n
000232
Intercept Tor Production ob (yesnc) Anverpecatur Me BME Cignretestday Drinksday Years Worked Trighycerdes
RAG=R=03<.00 "Natural log
Table 70 MualnidvOartihbelrePRoetegnrteisasliEoxnpMloandaetloroyfTV4ar*ibayblTesOF. for Amwe2r0p00anMdDeediccaatluSruMnavlilaEnmcpeloPyreoegrPaarmticipants,
emer se
vale
2260
0090
<0
[re
0006
Ed
-0005
0023
2
0010
[
-0003
0002
0
0001
[3
o
0001
00009
a
002
Poon
ot
0001
[TX
=
0010
oon
8
Pug3s 1C01on0p1e2n1y
Paral R* . <0 <0 <0 <0 <ot <0 <or <0 <ot
000233
-- Inereept pros Production Job (peso) AntwerpDecator Ase BMI Ciguretesday Drinkslday Years Worked Trighyeerides
RA0R6= 04 "Natural log
abl7e1 `MulivaanridsObtlheReergProteesnstiioanlMEoxdplealnoaftoFrryeeVaTr4iabblyesPFOS for Antwe2r0p0a0nMdeDdeiccaatuSruMrvaeliellEamnpceloPyreoegrPaamrticipants,
Pam 0299 -0004 -00% 0021 -0003 -0003 -00009 0006 0002 0003
SE
patie
0076
<0
[3
0019
n
0020
2
ooo
8
[2
a
00008
Ed
0010
Ej
0001
2
oo
8
Pag5eMiC0o2m1pa1n2y1
Paral B <0 <ot o <0 <0 <0 <ot <0
000234
3
Te? Muliv"andblOetrRegeresnsieon MEoxdpellaosfFtrsysVTari*albeysPFOA for AntwSe0r0n0deDelctSuMavlilEacmsplroogyrPamarga,
Co ewes
puke
nee
om
ous
oon
Pron
0006
006
a
Producion ob eso) 002s
oor
1
AnverDecatc
017
tom
a
A
000
ool
ot
00m
om
2
Cipretesty
~00009
aco
2
Dinky
omg
ooo
5
:
Year Worked
om
oar
Tigres
0001
oot
WAegre
init
[reer
Pani . a <0 @ on <a <on <a <n <a
000235
Pa3sMtCoormpeainnys
Tens
||
MulivfaoirsAbnlatenwdeRreOgprseensdsiPDoeencnMaotiudlrelMEoxafpelFarEnemaptToldroyyeVbasyrPiPaabFilOcesSpaatds,PFOA
2000 Medical Suveilanc Program.
|
-
09
pros
~00005
| POA
"0006
Production Job(yes/no)
0025
AntwerpDecatur
-000
Ase
-0003
Mr
-000
Ciguretesday
00009
Drinks/day
0.006
Years Worked
oon
Trgycerides
oon
Ria, a
Noes
om
000s oon
0020
0210 oon 0002 00mg
0010
oon oo
1
:
on
-
Es
<ot
=
<0
21
<01
"
@
o
E
<or
2
on
4
<1 |
FE)
<ot
mn
<or
000236
Inept Tor. Productiloonb (yes)
re i er Drinksday YearsWorked Trigleerdes
AR=R06 "Naural og
Table 4 MalivaanrdiOatlheerRePgorteesnstiiaolnEMxopdlealnotfoFryrVeaTr4isbbeysTOF for Antwe2r0p00ndMeDdeiccaatluSruMravleiellEamnpceloPyreosgrParmicipants,
Parameter
se
pualie
0299
0076
001
-0004
[es
2
-oms
000
a9
-0003
0001
-0003
000
a3
00009
00008
zn
0006
0010
Lo
oo0z
000
1
0004
[
a
:
Pu5sM0C5on0pa1a31y
Paral . on <ot
on <on <oi <ot <on <0
000237
_ een ros Production Job he) AnverDecaur I oa Cpmesiay Dinksday Years Worked Tigers
RAR-Es 34 "Nand
Tables MulivaanrdiOatlheerRePgrecssiionEMxopdlealnaotforTyHVEaRribeysPFOS for AneSr00n0dMeDteicsaal iSuMrvaeliellEanmcpelProoygrPaamicipans,
Parmeter
se
puae
3589
00
<oont
0003
oon
"
0006
000
5s
~00
oon
<0
~0o00s
ooms
PF
~o001
oor
~00007
oot
5
001s
00s
os
~o0m2
00007
mn
0003
oo
5
Page106.f 121 '
pani <a 0 <a <a <on a <a <a
000238
Inereept PrOA Production Job (yes) AntwerDecatur Age Mt Cigarettstday Drinkslay Years Worked Trighyeerides
RAGaRs=M "Nur log
Tale 76 Multiv`anrdiaObtlheeRrePgorteesnstiioaln EMxopdlealnaotfToryHVaRriabblyesPFOA for Antwe"r2p00a0nMdDedeiccaatluSruMnavlcilElmncpeloPyreoegrPaamtiipants,
Parameter
se
pile
2589
oon
<.001
-0003
[re
#
~0006
0010
EY
-008
oon
<.0001
-00005
00008
a8
-0001
001
2
-00007
, 00004
13
oats
000s
004
-0002
00006
an
-0on
008
6
PaMs 0C7o0mp1a2n1y
Paral B* 0 <on <ot <on <0 o <or <0
000239
st8 0FON REE a wv s ow Paonomenter sonees po"palue | nor es on aan a"
] oJ nAge
oio0.0006.
aor0.0008
a"a
Rrait
onns ije
RAiG=R3I5= 34
.
-
cee
: 0Partial wn
<0!
w. wn
Table 78 MuliavnardiOstbhleerRePogtreenstsiiaolnExMpoldaenlatoofTryHVaBriRablbeysTOF for Antwe"r2p00a0nMdeDdeicactauSrurMvaeliellEamnpceloPyreoegrPaamrticipants,
Parameter
se
pualue
Inercept
asso
oo
<0001
TOF
-0003
0003
2
Production ob (yesino)
-0004
oon
a)
AnwerpDecatur
-o0s8
oon
<.0001
|
Ase
-00006
00008
as
BMI
-0001
0001
a8
Cigaretesiday
-00007
00004
3
Dinkslday
oots
0005
004
Years Worked
-00002
00007
mn
Trglyerides
-0002
0008
0
RA=GR3=5 34 Natural log
Pu3MC1o09m0p0a1n21y
Panial 3 05 <0 2 <0 <0 <0 or <0 <0
000241
Table?
MalainvdriOtbhleer RPeogternetsisailoEnxMploaneatoorfyFTVaIr*ibayblPesFOS
]
for Antwe"r2p00s0nMdeDdeiccaatluSrurMvaeilllEamnpceloPyreoegrPaamrticipants,
|
ee
vumee
SE
pase
Inereept
129
008s
<o001
pros
-0006
0009
as
Production Job (yesh)
0009
oo
os
Anwerpecaur
007
002
0004
|
he
ous
oo
o
Bt
-00001
oo0z
9%
Ciguretestday
[
00009
82
]
Drinkslday
-0008
oon
"
Years Warked
oor
oor
a
lly!
[I
nnn
In
em
:
A "Naturw al log
Partial &* . o <ot o
@
<ot <ot <or <n
0
000242
: ew R..iirevd
|
Molise Regrsion od of TibyPOA
|
(ocAgnanDecctsMaotoEnlroeen FaiPnatipnt,s,
en
\ Parameter
oSoEn.
won
wom
oom
Pobeionkbhe) 0012
|J
J
oon
-
om
oon
|
wn
oto oon
os o cnom .on pvalue
Partial R*
on
Dry Cigareties/day
om0.0002
aon0.0009
"80
on<01
Yon Woes
om
oon
.
Py
i -- wom oo 1s wo
fri R'=.10
Adj R= 08
000243
||
nen
y
Mu IEpre ie WAre ltivariable Regression Model of FTI* by PFOS and PFOA
ee
ee
paow
asaess
p<unne
mos
a
om
o
ron
aor
os
|
| potion) -o00
om
-
mens
oom
om
wo
fot
os
on
wa
ogo
on
"
pees
oro
gos
o
pina
ooo
-
"
Voor
oon
wi
"
Ti
oom
ons
n
R'=.10
AdiR'= 08
*Natural log.
wiz
Part}ial B " wn wo " o wo I" m or
000244
Table 82 MuulinvdarOibsebrl PRegtresesioEnxpMloadnesltoorfFy TVIai*sblyeTs OR forAnwe2r0anMdeDdeiccaatluSruMrvaeeillEamnpceloPyreoegPaamrticipants,
|
_
emer
SE
pane
ree
129
008s
<oo01
Tor
0003
0006
a
Production ob ese) -o0i0
oon
AntweDecatur
~007
oo
on
I
-0003
3 oon
0
1
~00001
oon
1
Cigaretestay
[
00009
5
Drinksisy
0008
oon
"
Years Warked
oot
oon
"
geod
oon
0016
6
wAG=R1I0= 08
.
Non log
rCaosmpar
Paria N on <ot 0 @ <n <0 <or <n <0
000245
Table 3 forMAunlitinwvedarrOpstsbhlenrdPRDoetegecrnatetisuasrliEoMnxlMepodlEemalplonfoyVTsea3tsr#iPoabahyrreiPyscFipOnSts,
2000 Medical Surveillance Program
ee pewmeer
[--
am
SEC
. oon
puke
<.o001
pros
oo1s
oon
o
Production Job yesho)
[a
oo
AnwerpDecatur
009
oo
<oo0
ee
-0002
0001
2
Bl
00s
oon
Cigartestiny
0003
00008
wo
Drinksday
002
0009
os
YearsWorked
-00006
0001
Tglyerides
0020
oon
as
RMi=.R1=2 10
Natural log
Fae0iCoor p5y)
PwidR
. o o 0 <ot o <or <ot
000246
1 ||
Table 84 `Mul"iavnadrOitahbeler RPoetgernetsisailoEnxpMloadnesltoofrTy3Va*rbiyablPeFsOA for Antwe"r2p00a0nMdeDdeiccaatluSruMrvaeliellEamnpceloPyreoegrPaarmticipants,
Paes
SE
pualoe
Inercept
4
, oom
<0001
Poa
0016
0006
o
Production 1b (esha)
ois
0019
a
AnmwerpDecatur
-0109
00
<.0001
Ase
-0001
0001
=
BMI
000s
oom
o
Cigaretesday.
0003
00008
oo
Drinksday
008
000
0
Years Worked
00001
001
0
Trglyeridess
oois
, oou
2
RAGEag=. "Natural log
Pa3MgCeomlpa1n2y1
Paria B 0 <0 0 <0 0 o o <0 <0
000247
---- ess
| OeMPeadachlaopsyFoVgrrons for Antwerp and Decatur Male Employee Participants,
--_--
eePaeter
SE
pwle
J.
an
oom
<oon
wos
ao
TM
wou
oon
oo
Ce
Production ob Ges) oon
aon
Avene
"009
ono
<oon
TM
"aon
I
5
a
00s
a2
on
Cipreestny
000s
aos
1
Dray
"os
oo
on
Years Worked
ooo
aon
iors
oon
oon
2
= 13
Ntiog
rar eotts
PamiaR
. o <a <a <a @ <a <a
000248
. Ties MoidlOvvear PReogrrescsioxnpMlondeolnoyfTV3#ibysTOF fo Ama0ndMeDdieacltSMutmEimopgrPaips,
Parameter
SE
p value
eens
wn
oom
<0
Tor
oon
Production Job etc) oon
AntweDecae
"000
ae
or
at
oes
os
oot
oon
Cs
oo
<n
ool
3s
002
on
| Cipretestiny
ows
oom
TM
Dinky
"oo
os
w
Vous Worked
"oon
oon
56
Tete
oon
oo
2
AR R=. 13
i
ecMtCsmpan
iPartial R? <a <a @ <a <n
000249
.
2eaz3eVLCgoomfp|a
FMiagluereEm1.p.lLoiyneeeasr,R2e0g0r0esMseidoincaMlodSeurlvoefilTlraingclegyPcreroigdreasm* by PFOA* for Antwerc:
nn
RT 55
*
Lt.
E2N] s _...ag th :
.
wT. aT
n LARIRIS AFAR AERA wi
Summary of Fit
RSquare ~
0.029
-
Analysis of Variance
Source Model
Error CTotal
DF 1
204 205
Sum of Squares 1.863
61.193 63.056
Mean Square 1.863 0299
_F Ratio 6.211
Prob>F 0.014
Tem
Intercept In PFOA
ParameterEstimates
Estimate Std Error _tRatio Probolt
4.695
0.042 11143 <0001
0.073
0.029 249 0.014
"naturallog
000250
.
Pag3eMLC1o9omfpa1n3
Figure 2. LinEemarplRoeygereess,si2o0n0o0fMTeridgilcyaclerSiudrevse"ilblyanPceFOPAro*grfoarmDecatur Male
"0
x
0
soa
5
Lose
gE
-
oh
Fs
Sa Ee
.
is
:
Le
TH wma ouamon nw
Summary of Fit
RSquare
0.028
---
Analysis of Variance
SMoouderlce
Error CTotal
DFI Sum of Squ2a.r1e6s4 Mean Sq2ua1re666F2R3at2io
213
73.969
0.347 Prob>F
214
76.133
0.013
Parameter Estimates
Tem Intercept
In PFOA
Estimate 5.052
0.098
Std Error _t Ratio
0.041 12227
0.039
2.50
Proba|f] <.0001 0.013
*natural log
000251
.
=zsg3eM1C20o0mfp1a2r
. Figure 3. Linear Regression of Triglycerides" by PFOA" for Antwerp anc: Deczss--Female Employees, 2000 Medical Surveillance Program
TM
0
.
el
:
ym t ee h
:n SFE t AT as sin
`Summary of Fit
RSquare
0078
Source Model Error
C Total
Analysis of Variance
DF Sum of Squares Mean Square _FRatic
I
2.519
2519 80I0
95
29877
0314 Prob>E
9%
32.39
0.0065
Tem
Intercept
In PFOA
Parameter Estimates
Estimate Std Error _t Ratio_Probolt
4.690 0081 58.14 <0001
0.091
0.032 2.83 0.006
*nawral log
.
000252
Figure 4. Linear Regression of Triglycerides* by PFOA" for Cottage Grove Male Employees, 2000 Medical Surveillance Program
5
Ln ..
0
EN
$s10t gpanara
PETE
.
"
J
3
n ~i
--
RSquare
0.008
=
Source Model Error C Total
Tem Intercept
In PFOA
Analysis of Variance
DF _Sum of Squares Mean Square
1
0.452
0452
129
54.251
0421
130
54.704
F Ratio 1.076
Prob>F 0.302
Parameter Estimates
Estimate 5.022 0.032
Std Error _t Ratio
0.057 88.04
0.031
1.04
Prob>t] <0001 0.302
"natural log
000253