Document KOX73NNB3QgxXmew85ybmM32
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FINAL REPORT Epidemiology, 220-3W-05
Medical Department 3M Company
St. Paul. MN 55144
Date: October 11, 2001
Title: A Longitudinal Analysis of Serum Perfluorooctanesulfonate (PFOS) and Perfluorooctanoate (PFOA) Levels in Relation to Lipid and Hepatic Clinical Chemistry Test Results from Male Employee Participants of the 1994/95,1997 and 2000 Fluorochemical Medical Surveillance Program
Study Start Date: July 1, 2001
Protocol Number (not applicable) FRB Approval
Exempt E: - edited X
IRB Approval Date: (not applicable as these data are from a medical surveillance program)
Principal Investigator Co-investigators:
Study D irector
Geary W. Olsen, D.V.M., Ph.D.'
Michele M. Burlew, M .S.1 Jean M. Bums, R.N., M.P.H.1 Jeffrey H. Mandel, M.D., M.P.H.1
Jeffrey H. Mandel, M.D., M.P.H.1
1. 3M Medical Department, 220-3W -05, St. Paul, M N 55144-1000 ' (Conections made from previous version)
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f
Exhibit 1799
State of Minnesota v. 3M Co., Court File No. 27-CV-10-28862
3M MN02482163
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ABSTRACT
,
The 3M fluorochemical medical surveillance program was conducted in 1994/95,
1997 and 2000 at the company's Antwerp (Belgium) and Decatur (Alabama)
manufacturing plants. Although cross-sectional assessments of the data have been
reported, the opportunity to conduct a longitudinal assessment became possible as a result
of a large number of employee participants in the 2000 fluorochemical medical
surveillance program. A total of 175 male employees voluntarily participated in the 2000
program and at least one o f the two previous program years. A total of 106 (61 percent)
of the 175 employees participated in the 1994/95 program and 110 (63 percent) o f the
175 participated in the 1997 program. O f these 175 employees, a total of 41 (24 percent)
participated in all three years (Antwerp = 21, Decatur = 20), 65 (37 percent) participated
in 1994/95 and 2000 (Antwerp = 45, Decatur = 20) and 69 (39 percent) participated in
1997 and 2000 (Antwerp = 34, Decatur - 35). There were insufficient number of female
employees to conduct any meaningful longitudinal assessment. Only 14 female
employees participated in the 2000 fluorochemical medical surveillance program and at
least one of the previous program years. Serum perfluoiooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) were
assayed in each surveillance program year although the method of analysis (high
performance liquid chromatography mass spectrometry) differed slightly between years.
A different research laboratory was used to assay PFOS and PFOA in each year.
The same hospital laboratory analyzed the clinical chemistries for all three
surveillance years. These included: cholesterol (mg/dl). high density lipoproteins (HDL,
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3M Company Page 3 of 63 mg/dl) and triglycerides (mg/dl); 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). Most reference ranges remained relatively constant over time except for ALT. In each surveillance year, potential confounding factors were also determined. These covariates included age, body mass index, number of alcoholic drinks per day and cigarettes smoked per day. The continuous outcomes o f lipid and hepatic clinical chemistry tests were evaluated as repeated measures incorporating the random subject effect fitted to a mixed model by the MIXED procedure in the SAS statistical package. Restricted maximum likelihood estimates of variance parameters were computed. Adjusted regression models were built by introducing all covariates and testing the covariance structure. Significant coefficients were defined when the p value was < .05. There was a positive association between PFOA and serum cholesterol and triglycerides over time but not with PFOS. This was association was limited to the Antwerp employees and, in particular, the 21 Antwerp employees who participated in all three surveillance years. This positive association between PFOA and serum lipids is opposite the inconsistent toxicological evidence that suggested a possible hypolipidemic effect of PFOA in rodents and no effect in primates. Adjusting for potential confounders, there were no temporal changes associated with the fluorochemical tests, PFOS, PFOA and TOF, and the hepatic clinical chemistry tests. Limitations of this study included the number o f employees with three years of surveillance data (only 24% of the 175 subjects), the inability to analyze temporal changes due to small numbers in female employees, the use o f different laboratories and
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the associated systematic (experimental error) with each fluorochemical assay for the
three surveillance program years and the lower levels of serum PFOS and PFOA
.
measured in each program year among these employees compared with those that cause
effects in laboratory animals.
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INTRODUCTION
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The 3M fluorochemical medical surveillance program is conducted on a routine
basis at the company's Antwerp (Belgium) and Decatur (Alabama) manufacturing plants.
Employee participation is voluntary. Prior to 1994, only total organic fluorine was
measured and no specific fluorochemical analytes were measured. Serum
perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) have been routinely
assayed since 1994/95 rather than total organic fluorine as the analytical capabilities have
improved. Cross-sectional analyses of the 1994/95 and 1997 medical surveillance
program data and the 2000 data in relation to Antwerp and Decatur employees' serum
PFOS levels have been reported elsewhere (Olsen et al, 1999a, 1999b, 2001). In the
1994/1995 medical surveillance program, a total of 178 male employees participated
(Antwerp = 88; Decatur = 90) and 149 male employees participated in the 1997 program
(Antwerp = 65; Decatur = 84). For these two program years, there were too few female
participants to include in the data analysis (Olsen et al 1998). In the 2000 fluorochemical
medical surveillance program, there were considerably more participants: 421 males
(Antwerp = 206; Decatur = 215) and 97 females (Antwerp = 49; Decatur - 48). It was
suspected that the increased voluntary participation in 2000 was due to increased
employee awareness o f the persistence and prevalence of PFOS in human tissue and the
environment and the com pany's May 16. 2000 phase out announcement that it would
cease the production o f perfluorooctanyl chemistry in certain repellents and surfactants
by the end of 2000.
Regardless of the surveillance year, there have been several consistent differences
between the Antwerp and Decatur male employee populations. The Antwerp male
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3M Company Page 6 of 63 employee population has been significantly younger than Decatur, has had lower Body Mass Indices (BMI) and higher self-reported daily consumption of alcohol. In addition, the Antwerp male employee population clinical chemistry profiles were different for several tests including lower mean alkaline phosphatase and triglyceride values and higher total bilirubin and HDL values than the Decatur male employee population. Analyses o f workers' lipid and hepatic clinical chemistry results have not been associated with hypolipidemic effects and PFOS as reported in rodents (3M Company 2000; Haughom and Spydevold 1992; Ikeda et al 1987; Pastoor et al 1987; Seacat et a] 2001a; Sohlenius et al 1993) and primates (Seacat et al 2001b). In the 2000 medical surveillance program, statistical analyses also examined the relation between PFOA and a calculated total organic fluorine index (TOF) to clinical chemistries, hematology, thyroid hormones and urinalyses (Olsen et al 2001). A positive association was observed between triglycerides and PFOA; however, this association was opposite the data that have inconsistently reported a hypolipidemia effect of PFOA in rodents (Haughom and Spydevold 1992; Pastoor et al 1987) and no effect in primates (Butenhoff et al 2001). Furthermore, this positive association between PFOA and triglycerides has not been observed at the 3M Cottage Grove manufacturing plant (Olsen et al 2000) where employees' serum levels have, historically, been much higher than those measured among Antwerp and Decatur employees (Olsen et al 1999; 2001a; Olsen et al 2001b). The inability to assess temporal changes in cross-sectional studies is a wellknown limitation of this design. The large participation o f employees in the 2000 fluorochemical medical surveillance who may have participated in the 1994/95 and/or 1997 surveillance programs at these two manufacturing sites allowed for an opportunity
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3M Company Page 7 of 63 to conduct a longitudinal analysis among the male employee population. Altogether, a total o f 175 employees (Antwerp = 100; Decatur = 75) who participated in 2000 had also participated in at least one previous fluorochemical medical surveillance exam since 1994/95. Therefore, the purpose of this analysis was to conduct a longitudinal assessment of this 6 year time period regarding the relationship of PFOS, PFOA and TOF to the medical surveillance data collected on these 175 Antwerp and Decatur male employees.
METHODS Data Collection
Data were compiled fro m the 1994/95, 1997 and 2000 fluorochemical medical surveillance program databases. A total of 175 male employees participated in the 2000 program and at least one of the two previous program years. A total of 106 (61 percent) of the 175 employees participated in the 1994/95 program and 110 (63 percent) o f the 175 participated in the 1997 program. O f these 175 employees, a total of 41 (24 percent) participated in all three years (Antwerp = 21, Decatur = 20), 65 (37 percent) participated in 1994/95 and 2000 (Antwerp = 45, Decatur = 20) and 69 (39 percent) participated in 1997 and 2000 (Antwerp = 34, Decatur = 35). For purposes o f brevity, these three subpopulations will hereafter be referred to as subcohorts A, B and C.
Demographic data (age, BMI, alcoholic drinks per day and cigarettes per day) were recorded for each employee in each surveillance year. A standard set o f clinical chemistries and hematology data was also obtained for each employee. Given results from previous toxicological studies, the longitudinal analyses focused on lipid
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3M Company Pags 8 of 63 [cholesterol (mg/dl), high density lipoproteins (HDL, mg/dl) and triglycerides (mg/dl)] and hepatic [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)] clinical chemistries that were measured in each program year by the same laboratory (Allina Laboratories, St. P au l, MN). Reference ranges were relatively constant over time, although for ALT the range declined from 20-65 IU/L in 1994/95 to 1-40 IU/L in 1997 and 2000.
Fluorochemical Analyses PFOS and PFOA were assayed in 1994/95,1997 and 2000. However, the method
of analysis differed slightly for each year. In 1994/95, the method used tetrabutylammonium to ion-pair with PFOS and PFOA in the serum (Johnson et al 1996). The ion-pairs were then extracted with ethyl acetate. The abstraction product was then analyzed using high-performance liquid chromatograph-thermospray mass spectrometry. In 1997, the serum samples were analyzed by liquid chromatography/mass spectrometry, using selected ion monitoring in the negative-ion mode (Anderson and Mulvanna 1997a; 1997b). In 2000, sera samples were extracted using an ion-pairing extraction procedure (Hansen et al, 2001). Only in 2000 were the extracts quantitatively analyzed for PFOS and PFOA as well as the other analytes: PFHS((perfluorohcxanesulfonate), PFOSAA (Nethyl perfluorooctanesulfonamidoacetate), M570 (N-methyl perfluorooctanesulfonamidoacetate), PFOSA (perfluorooctanesulfonateamide) and M556 (perfluorooctanesulfonamidoacetate). High-performance liquid chromatography/electrospray tandem mass spectrometry (HPLC/ESMSMS) was the
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3M Company Page 9 of 63 technique used in 2000. The samples were evaluated versus an extracted curve from a human serum matrix. Analyses were conducted at different laboratories in the three surveillance years. For purposes of this longitudinal analysis, a total organic fluorine index (TOF) was determined by calculating the percent of PFOS and PFOA that was attributed to organic fluorine (64.7 and 69.0 percent, respectively) multiplied by the ppm . measured for each of these two fluorochemicals and then summed to produce the TOF.
Data Analysis
Briefly, mixed models can be used in the analysis of repeated measures data
which are simply data sets with multiple measurements of a response variable on the
same subject over time. Detailed explanation of these models is provided elsewhere
(Littell 1996; 2000). Mixed models contain factor effects which are considered both fixed and random. An effect is fixed if the levels in the study represent all possible levels
of the factor, or at least all levels about which inference is to be made. Factor effects are
random if the levels o f the factor that are used in the study represent only a random
'
sample of a larger set of potential levels.
The focus o f the standard linear model is to model the mean of y by using the
fixed-effects parameters f3. That is,
y = X/3 + e
where y represents a vector o f observed data, /3 is an unknown vector o f fixed effects
parameters with known design matrix X, and e is an unknown random error vector
modeling the statistical noise' around XjS. The residual errors e are assumed to be
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3M Company Page 10 of 63 independent and identically distributed Gaussian random variables with mean 0 and variance a 2. A generalized standard linear model is a mixed model which is: y = X/3 + Z y + e where y is an unknown vector of random-effects parameters with known design matrix Z , and 6 is an unknown random error vector whose elements are no longer required to be independent and homogeneous. If y + e are assumed to be Gaussian random variables that are uncorrelated and have expectations 0 and variances G and R, respectively, then the variance o f y is: V = ZGZ'+ R The variance of the data, y, can be modeled by specifying the structure of Z, G and R. The model matrix Z is designed in the same fashion as X, the model matrix for the fixedeffects parameters. For the matrices G and R, a covariance structure must be selected in using mixed models. Since observations on different subjects are assumed to be independent, the structure refers to the covariance pattern of repeated measurements on the same subject. For most of these structures, the covariance between two observations on the same subject depends only on the length o f the time interval between measurements and the variance is constant over time. Numerous covariance structures exist. Common examples include the following. Simple covariance structure (SIM) specifies that the observations are independent, even on the same subject, and have homogeneous variance. It is usually not realistic for most repeated measures data because it specifies that observations on the same subject are independent. Compound symmetric (CS, otherwise
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3M Company Page 11 of 63 known as variance components) structure specifies that observations on the same subject have homogeneous covariance and homogeneous.variance. Correlations between two observations are equal for all pairs of observations on the same subject. Autoregressive order 1 (AR(l))covariance structure specifies homogeneous variance but that covariances between observations on the same subject are not equal, but decrease toward zero with increasing time interval between measurements (lag). Its limitation is that observations on the same subject far apart in rime would be essentially independent. Autoregressive with random effect for subject (AR + RE) covariance structure specifies homogeneous variance plus the covariance between observations on the same subject arises from two sources: 1) any two observations share a common contribution because they are on the same subject; and 2) the covariance between observations decreases exponentially with lag but only to the common contribution (not to independence). Toeplitz (TOEP) structure specifies that covariance depends only on lag but not as a mathematical function with a small number o f parameters. The 'unstructured' structure (UN) specifies no patterns in the covariance matrix and is therefore completely general. The above structures are appropriate if equal spacing (of data) is assumed in a time series analyses. In situations where unequally spaced longitudinal measurements exist, spatial covariance structures can be used. In the present analyses, equal spacing was assumed given there were approximately 3 yean between each medical surveillance program examinations. Akaike's information criterion (AIC) and Schwarz's Bayesian criterion (SBC) are indices o f relative goodness-of-fit that were used to compare models with the same fixed effects, but different covariance structures. SBC penalizes models more severely for the
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3M Company Page 12 of 63 number of estimated parameters than AIC and thus the two criteria did not always agree on the choice of-best' model. SBC was preferred. In the present study, the continuous outcomes of lipid and hepatic clinical chemistry tests were evaluated as repeated measures incorporating the random subject effect fitted to a mixed model by the MIXED procedure in the SAS statistical package (Littell et al 1996). Restricted maximum likelihood estimates (REML) of variance parameters were computed. Adjusted regression models were built by introducing all covariates (see below) and testing the covariance structure. Based on goodness-of-fit tests described above, AR+RE, was routinely considered the best covariance structure chosen for the mixed models. Covariates included PFOS (or PFOA or TOF), years of observation, the-interaction term of PFOS and years of observation, age, body mass index (BMI), cigarettes smoked per day, alcohol drinks per day, year at first entry and baseline (at First observation) years worked. For hepatic clinical chemistry tests, serum triglycerides was also considered a covariate (Olsen et al 2001a).
RESULTS Provided in Table 1 are cross-sectional analyses of the study subjects who
participated in each of the three years (1994/95,1997 and 2000) stratified by location. As reported previously in the complete cross-sectional analyses o f these programs (Olsen et al 1998; 1999; 2001), Antwerp employees in this longitudinal investigation were younger, had lower BMIs and drank more alcoholic beverages than Decatur employees. They also had consistently lower triglyceride and alkaline phosphatase levels and higher HDL and total bilirubin levels. Decatur employees, on average, had serum PFOS levels
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3M Company Page 13 of 63 that were higher by approximately 0.5 ppm in each cross-sectional analysis. Similar findings were observed for PFOA except with the 1997 data where the two populations had comparable mean PFOA levels. Provided in the following two tables are the cross-sectional analyses for the three subcohorts by location. Among Antwerp employees (Table 2), each of the three subcohorts had lower mean serum PFOS levels in 2000 than at their year o f entry whereas there were no consistent changes across subcohorts with PFOA. Among the three Decatur subcohorts (Table 3) mean PFOS values declined over time but mean PFOA levels tended to increase. Provided in tables 4 through 30 are the mixed model coefficient estimates, standard errors, p-values and 95% confidence intervals from testing potential determinants of lipid and hepatic clinical chemistry change. The natural log was used for all dependent variables. Tables 4 through 6 contain the analyses for cholesterol. There was no change in cholesterol associated with PFOS (Table 4). Overall. PFOA was positively associated with cholesterol as the main effect coefficient was significantly positive but its interaction with time (years variable) was negative (Table 5). Provided in Tables 5A through 5D are separate analyses for Antwerp for all subjects (Table 5A) and by each subcohort. The PFOA and cholesterol association appeared to primarily reside with the 21 Antwerp employees in subcohort A (Table 5B). This finding can also be observed in Table 2 as the subcohort's mean PFOA levels went from 1.32 ppm. to 2.37 ppm and then declined to 2.06 ppm at the same time their cholesterol values rose from 208 mg/dL to 226 mg/dL to 229 mg/dL. There were no associations between cholesterol and PFOA observed among
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3M Company Page 14 of 63 the Decatur employee population (Table 5E) nor were there significant associations between TOF and Antwerp or Decatur but when the two sites were combined there was a significant positive association between TOF and cholesterol (Tables 6 ,6A and 6B). There were no significant associations between PFOS, PFOA or TOF with HDL (Tables 7 through 9). BMI, alcoholic drinks per day and cigarettes smoked per day were the most significant associations with HDL. Triglycerides were not significantly associated with PFOS over time when both Antwerp and Decatur populations were examined together (Table 10). However, among the combined Antwerp and Decatur populations, PFOA was positively associated with triglycerides (Table 11) as seen with the significant positive coefficient for the main effect of PFOA and the nonsignificant positive main coefficient of years and the negative coefficient for their interaction (PFOA x years). The significant main effect of PFOA was the consequence of the Antwerp population (Table 11A) and primarily subcohort A (table 1IB) and, to a lesser extent subcohort B (Table 11C), but not subcohort C (Table 1ID). Therefore, the association appeared to be related to the Antwerp workers who were enrolled in this longitudinal cohort beginning in 1995, but not 1997. There was not a significant association between PFOA and triglycerides among Decatur workers (Table 1IE). Among the Antwerp subcohort A, their mean triglyceride levels rose from 85 mg/dL to 115 mg/dL to 123 mg/dL at the same time their PFOA levels increased from 1.32 ppm to 2.37 ppm and then declined to 2.06 ppm. Although the main effect for TOF was significantly positive, the interaction term with time (years) was not significant (Table 12). Again, this association was more consistent for Antwerp employees (Table
i
12A) than Decatur employees (Table 12B).
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3M Company Page 15 of 63 Among the hepatic clinical chemistry tests that were adjusted for the various changing demographic factors and triglyceride levels, there were no significant associations between PFOS, PFOA andTO F with changes in alkaline phosphatase (Tables 13 - 15), GGT (Tables 16-18), AST (Tables 19-21), ALT (Tables 22-24), total bilirubin (Tables 25 - 27) or direct bilirubin (Tables 28-30). Observations apparent in Tables 2 and 3 can also be seen in these mixed model analyses. For example, the two most significant predictors of alkaline phosphatase were time (years) and location (as seen with the lower values among Antwerp employees). For ALT, entry period was also significant as it reflected the higher reference range values for ALT that were used in 1994/95 than in subsequent years.
DISCUSSION These analyses were the first longitudinal assessment of the fluorochemical
medical surveillance program at 3M's Antwerp and Decatur manufacturing sites. Overall, we observed no associations that were consistent with the toxicological evidence that PFOS produces a hypolipidemic effect at threshold dosages in rats and primates (3M Company 2000; Haughom and Spydevold 1992; Ikeda et al 1987; Pastoor et al 1987; Seacat et al 2001a; 2001b; Sohlenius et al 1993). Our results did suggest a positive association between temporal changes in cholesterol and triglycerides and PFOA; however this is also inconsistent with the toxicological evidence that PFOA may result in a hypolipidemic effect in rats (Haughom and Spydevold 1992: Pastoor et al 1987) but produced no effect on blood lipids in primates (Butenhoff et al 2001).
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3M Company Page 16 of 63 Even though we were able to perform a longitudinal assessment, there were several limitations to our analyses. We were limited to 175 employees of which only 41 (24 percent) participated in all three surveillance years. Although a greater absolute number of Decatur employees (but not percent-wise) have participated during each year, for this longitudinal assessment there were more Antwerp (57 percent) than Decatur (43 percent) employees. Antwerp employees have had lower serum PFOS level by approximately 0.5 ppm (Olsen et al 1998; Olsen et al 1999a; 1999b; 2001a; 2001b; 2001c). There were insufficient numbers of female employees for any meaningful longitudinal analysis. Given the variability inherent in the analytical method (Hansen et al 2001) and the different laboratories used, serum PFOS and PFOA levels may have systematic error incorporated in each measurement that we were unable to assess as blood samples were analyzed only at the time of the surveillance program. This systematic error may have masked associations with lipid or hepatic clinical chemistries, although the range of PFOS and PFOA measured was relatively consistent throughout the study time period. Because 3M has announced a phase-out of the production of perfluorooctanyl chemistry-related materials, we doubt that there will be many more subjects in the future that can be included in this longitudinal assessment. Also, the findings from this assessment would suggest that serum PFOS levels have either remained constant or declined slightly over time among these 175 employees. On the other hand, serum PFOA levels appeared to trend upwards, on average, by approximately 0.5 to 1.0 ppm for these employees. Another limitation is the fact that the serum PFOS and PFOA levels measured in these employees were lower than those that cause effects in laboratory animals.
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In summary, a longitudinal analysis over a six year time period o f 175 Antwerp and Decatur male employees did not show significant changes, consistent with toxicological data, of lipid or hepatic clinical chemistry values associated with either PFOS or PFOA. The PFOS and PFOA serum levels measured in these employees were lower than those that cause effects in laboratory animals.
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REFERENCES
3M Company Page 18 of 63
3M Company (2000). SIDS Initial assessment report: Perfluorooctane sulfonic acid and its salts. St. Paul (MN):3M Company, (unpublished report). Minneapolis (MN):University of Minnesota, (unpublished report).
.
Anderson DJ, M ulvanaD E (1997a). Analytical Report for the Determination of Perfluorooctanoate and Perfluorooctanesulfonate in Human Serum by LC/MS. Ithaca NY:Advanced Bioanalytical Services Inc; August 1997.
Anderson DJ, Mulvana DE (1997b). Analytical Report for the Determination of Perfluorooctanoate and Perfluorooctanesulfonate in Human Serum by LC/MS. Ithaca N Y :Advanced Bioanalytical Services Inc; September 1997.
B utenhoff JL, Costa G, Elcombe C, Farrar D, Hansen K, Iwai H, Jung R, Kennedy G, Lieder P, Olsen GW, Thomford P. Toxicity of ammonium perfluorooctanoate (APFO) in cynomolgus monkeys after 26 weeks of oral dosing, (unpublished report)
Hansen KJ, Clemen LA, Ellefson ME, Johnson JHO (2001). Compound-specific, quantitative characterization of organic fluorochemicals in biological matrices. Environ Sci Technol 35:766-770.
Haughom B, Spydevold O (1992). The mechanism underlying the hypolipemic effect of perfluoroctanoic acid (PFOA), perfluoroctanesulphonic acid (PFOSA) and clofibric acid. Biochemica et Biophysica Acta 1128:65-72.
Ikeda T. Fukuda K, Mori I, Enomoto M , Komai T, Suga T (1987). Induction of cytochrome P-450 and peroxisome proliferation in rat liver by perfluorinated . octanesulfonic acid. In: P e rix o sm e s in B io lo g y a n d M ed icin e. (HD Fahmi and H Sies, eds) New York:Springer Verlag, pp 304-308.
Johnson JD, Wolter JT, Colaizy GE, Rethwill PA, Nelson RM. Quantification of Perfluorooctanoate and Perfluorooctanesulfonate in Human Serum Using Ion-Pair Extraction and High Performance Liquid Chromatography-Thermospray Mass Spectrometry with Automated Sample Preparation. St. Paul, M N:3M Env Lab, 1996.
Littell RC, Pendergast J, Natarajan R (2000). Modeling covariance structure in the analysis of repeated measures data. Stat Med 19:1793-1819.
Littell RC. Milliken GA, Stroup WW, Wolfinger RD. SAS System for Mixed Models. Cary N CSA S Institute Inc.. 1996, 633 pp.
Olsen GW. Burris JM, Mandel JH, Zobel LR (1998). 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).
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Olsen GW, Burris JM, Mandel JH, Zobel LR (1999a). Serum perfluorooctane sulfonate and hepatic and lipid clinical chemistry tests in fluorochemical production employees. JOEM 41(9):799-806.
Olsen GW, Logan PW, Simpson CA, Hansen KJ, Burris JM, Burlew MM, Schumpeit JC, Mandel JH (1999b). Fluorochemical exposure assessment of Decatur chemical and film plant employees. St. Paul:3M Company (unpublished report).
Olsen GW, Burris JM, Burlew MM, Mandel JH (2000). Plasma cholecystokinn and hepatic enzymes, cholesterol and lipoproteins in ammonium perfluorooctanoate production workers. Drug Chem Toxicol 23(4):603-620.
Olsen GW, Burlew MM, Burris JM, Mandel JH (2001a). A cross-sectional analysis of serum perfluorooctansulfonate (PFOS) and perlfuorooctanoate (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. St: Paul (MN):3M Company (unpublished report).
Olsen GW, Schmickler MN. Tierens JM, Logan PW, Burris JM, Burlew MM, Lundberg JK, Mandel JH (2001b). Descriptive summary of serum fluorochemical levels among employee participants of the year 2000 Antwerp fluorochemical medical surveillance program. St. Paul:3M Company (unpublished report).
Olsen GW, Logan PW, Simpson CA, Burris JM, Burlew MM, Lundberg JK, Mandel JH '(2001c). Descriptive summary o f serum fluorochemical levels among employee participants of the year 2000 Decatur fluorochemical medical surveillance program. St Paul:3M Company (unpublished report).
PastoorTP. Lee KP, Perri MA, Gillies PJ (1987). Biochemical and morphological studies of ammonium perfluorooctanoate-induced hepatomegaly and peroxisome proliferation. Exp Mol Pathol 47:98-109.
.
Seacat AM, Thomford PJ, Hansen KJ, Clemen LA, Case MT, Butenhoff JL (2001a). Sub-chronic dietary toxicity o f potassium perfluorooctanesulfonic acid in rats. Toxicol Sci (submitted 2001a).
Seacat AM. Thoford PJ, Hansen KJ, Olsen GW, Case MT. Butenhoff JL. Subchronic toxicity studies on perfluorooctanesulfonate potassium salt in cynomolgus monkeys. Toxicol Sci (submitted, 2001b).
Sohlenius AK, Eriksson AM, Hogstrom C, Kimland M, DePierre JW (1993). Perfluorooctane sulfonic acid is a potent inducer o f peroxisomal fatty acid B-oxidation and other activities known to be affected by peroxisome proliferators in mouse liver. Pharmacol Toxicol 72:90-93.
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I'POS
Ttiltlc I. ( Toss-Sectional Analysis of Mean and St.,....aid Deviation of Serum I'POS, IT'OA, TOP, Demographic Characteristics and Clinical Chemistries of Antwerp and Decatur Male Employees Who l'aitici|)atcd in Two or More Medical Surveillance Examinations Itelwccn 1994/95 and 2(KK)
1994/1995_________________
Antwerp (N = 66)
Decatur (N = 40)
. 1997
'
Antwerp (N = 55)
D ecatur (N = 55)
2000________________________________
A ittwerp ( N=1 Ot))
Decatur (N = 75)
Mean 1.87
SI) 1.96
Mean 2.62'
SD 1.78
Mean 1.42
SD 1.26
Mean 1.85
SD 1.64
Mean 1.16
SD 1.07
Mean 1.67"
SD 1.39
in-OA
I.OK 1.55
1.901' 1.08
1.54 1.61
1.41 1.17
1.4.4 1.21
1.83" 1.53
TOP
1.96 1.77
5.001'
1.77
1.98 1.48
2.17 1.76
1.74 1.24
2.34"
1.72
Age
36 (>.(> 4.4" 6.0 52
6.8 45" 7.3 38 7.K 4 7 ' 7.0
ItM l
2.4.9
2.4
28.0"
5.7
23.2
2.4
29.1"
4.3
24.7 2.K
29.0"
4.1
Alcohol
If* l.l
0.5 0.6
0.9" 1.0
0.1 0.1
1.1" 1.0
0.1 0.2
llaseline Years I t o
5.7
20.4"
7.1
W orked
Cigarettes 4 7
I01' 15
7.0 5.2 57
20.0" 5
6.1 10
9.1 6.1 58
2 0 . 3 "'
8.5
5 11
Cholesterol
2I7
45
219 38
202 45
214 35
220 41
213 4(1
DDL
54" 15
43 1.4
49" II
4.4 10
53" 12
44 10
Triglycerides
III
79
204"
122
108 5.4
181"
112
131 80
178` 115
"or*e
Aik I'ltos
72 IK
103"
27
68 15
20 58 14 74" 21
GOT
57 25
47 24
2.4 11
.45" 27 ' 25 19
29 18
AST
25 II
.41* 11
26 6
26 ' 8
24 7
25 7
ALT
44 17
49 25
50 12
52 15
23 11
32" 14
T otal Hilirtihin (1.9"
0.4
0.5 0.2
0.8b
0.4
0.6 0.2
1.0" 0.3
0.8 0.2
Direct IVilinihin 0.2
0.4
0.2 0.04
0.1" 0.07
0.1 0.04 0.1" 0.05 0.1 0.06
a. p < .05
h. p < .01
c. p < .0 0 1
d. p < .0001 com pared In year-specific analyses o f oilier m anufacturing site.
3M MN02482182
1799.0020
i*p o s
Table 2. Cross-Sectional Analysis of Mean ami Standard Deviation or .Serum 1'POS, I'POA, TOP. Demographic Characteristics anil Clinical Chemistries of Three Subgroups of Antwerp Male Employees (A, II and C)
Wlm I'arlicipnted in Two nr More Medical Surveillance Examinations Between 1905 and 2000
1995 ___________
1997
_____ _______________ 2000
A (N = 2 I)
It (N = 45)
A (N = 21)
C. (N = 34)
A (N = 21)
B (N = 45)
C (N = 34)
Mean SD
Mean SD
Mean SD
Mean SD
Mean SD Mean SD Mean SD
2 . 19 1.27
1.72 2.20
2.24* 1.32
0.91 0.93
1.53. 0.87 1.20 1.31 0.871' 0.71
pans o f tO
I'POA
1.32 1.28
0.96 1.64
2.37' 2.28
1.09 . 0.61
2.06* 1.04 1.17
1.37 1.38 0.94
TOP
2.33 1.20
1.78 1.98
.3.08* 1.59
1.31 0.91
2.41* 0.81 1.58 1.51 1.52 0.89
Age
33 fi
37" 7
35" 5 30 7
38" 6 42* 7
7
II Ml
23.4 2.7
24.1 2.3
23.8 2.8 22.7 2.0
24.3
3.4 25.5`
2.7 23.9
2.4
D rinks/day
1.3 1.4
HI 0.9
1.2 1.2
0.7 0.8
1.7" 1.3 1.2
l.l 0.8
(1.6
Cigaretles/day 4
7
48
57
57
6 84 8 5 8
Baseline Years W orked
9.9
4.3
11.6 63
9.9 4.3
5.3 4.9
9.9 4.3 11.6 6.3 5.3 4.9
Clioleslerol
208 46
220 41
226' 50
187 34
229 46 233' 38 196 31
DDL
56 II
5.3 13 51 9 48 11
56 12 52 11 52 13
Triglycerides 85
49
123 88
115 69
104 41
123 65 154 95 105 55
Aik Phos
60 20
73 16
67 19
69 12
55 17 60 14 58 12
GOT
30 9
41 29
25 10
22 II
23
13 301' 25
19
11
AST
25 5
25 13 26 5 26 7
22 5 25 9 23 6
ALT
42 8
46 20
31 12
30 13
22 II 25 13 21
7
Total Bilirubin HI 0.3
0.8 0.4
0.8 0.3
0.8 0.4
1.0 0.3 1.0 0.3 0.9 0.3
Direct Bilirubin 0.2 0.04
0.2 0.04
0.1 0.05 0.2. 0.08
0.1 0.0.3 0.1 0.06 0.1 0.06
/ISu is
l l o u i Mllior kakii
.... in rnrnr
h !\ /* n s itvtii iim\itn A
r i> <* flS ll>nn nrrm n P
3M MN02482183
1799.0021
I'F O S
Table 3. ( Voss-Sectional Analysis of Mean and Standard Deviation of Scrum I'POS, ITOA, TOP, IIcmcrgraptiic Characteristics and Clinical Chemistries of Three Subgroups o f Decatur Male Employees (A, I) and C)
Who I'urticipalcd in Two or More Medical Surveillance Examinations Between 1994 and 2000
iinpam 22 .>163
1994______________________________ 1997_______________ _______________________2000
A (N = 20)
B (N = 20)
A (N = 20)
C (N = 35)
A (N = 20)
B(N = 20)
C (N = 35)
Mean SD
Mean SD
Mean SD
Mean SD
Mean SD Mean SD Mean SD
2.02 1.67
3.17" 1.76
1.93 1.76
1.80 1.59
1.78 2.14 1.84
1.03 1.51 0.98
PFOA
1.50 0.87
2.30" 1.14
1.41 1.16
1.41 i 1.20
1.46 1.34 2.60* 2.02 1.60 1.14
TOP
2..17 1.54
3.64* 1.79
2.22 1.78
2.14 1.78
2.16 2.16 2.98
1.76 2.08
1.32
Age
42 7
44 5
45 7 42 8
48 7 50 5 45 8
HMI Drinks/day
2X.2 0.1
4.0 0.3
27.7 3.3 6.4 0.8
28.3
4.1
29.6
4.5
0.1 0.1
0.1 0.2
28.9 0.0
4.1 28.7 0.1 0.2
3.3 29.3 0.3 0.1
4.5 0.2
Cigarellcs/day 6
13
14 15
4 10
5 11
3 8 10 15 4 9
Baseline Years 19.6 Worked
8.6 .
21.3
5.2
19.6
8.6
20.2
10.0
19.6
8.6 21.3
5.2 20.2
10.0
Cholesterol
235" 34
204 36
223 31
208 37
228
39
199" 33
212
41
llD L
47" 16
39 9
45 11 41 9
47 12 38* 6 45
9
T riglycerides 180 88
229 148
188 115
178 112
193 124 187 76 165 128
Aik Blurs
98 29
107 24
85 22
87 18
70 27 82 17 72 20
(itiT AST
41 25 32 15
52 22 29 6
35 36 25 6
31 20 27 8
29
16 34
23 27
17
26 8 25 4 25 7
ALT
52 33
Total Hiliruhin 0.6 0.2
Direct Bilirubin 0.2" 0.05
47 11
30 15
34 16
0.5 0.2
0.6 0.2
0.6 0.2
0.2 0.04
0.1 0.04 0.1 0.05
30 0.8 0.1
18 32 0.2 0.7 0.08 0.1
11 33 0.2C 0.8 0.04 0.1
14 0.2; 0.06
. ^ OS tl.-n.
in w*-ir It n<- OS ilvin omiin A r it<r 1OSl!wn ornitn C*
3M MN02482184
1799.0022
J Company i'u g c 2 3 o f 63
Table 4. Mixed Model Coefficient Estimates, .Slandard Errors (SB), P-Vulues and 95% Confidence Limits from Testing Potential Determinants of Cholesterol* Change Including PPOS and the Interaction with Ninnlrer of Years of Observation or Antwerp and Decatur Male Employees
95% Confidence Limits
Coefficient
SK
p-vulue
Lower
Upper
Intercept
4.K68
0.127
<.0001
4.618
5.118
PPOS
' 0.010
0.008
.18 - 0.005 0.025
Years Observation
0.0009
0.005
.84 -0.008 0.010
PFOS x Years Obs
- 0.0004
0.002
.83 -0.004 0.Q03
Age
0.007
0.003
.01
0.002
0.013
BMI
0.006
0.003
.07
-0.0005
0.013
Drinks/day
0.014
0.012
.27 -0.011
0.038
Cigarelies/duy
- 0.0009
0.001
.41 -0.003 0.001
Location*
0.034
0.037
.36 - 0.039 0.108
Entry Period**
Baseline Years Worked
0.064 -0.004
0.028 0.003
. 02
.20
0.009 -0.009
0.119 0.002
`natural log Antwerp vs Decatur **1994/95 vs 1997
3M M N 02482185
1799.0023
, Company Page 24 o f 63
Table 5. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Cholesterol* Change Including PPOA and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
Coefficient
Sli
p-value
Lower
Upper
Intercept
4.KI2
0.127
< .(MM)1
4.561
5.063
PFOA
0.032
0.009
.0008
0.013
0.051
Years Observation
0.005
0.005
.24 -0.004 0.014
PFOA x Years Obs
- 0.005
0.002
.005 -0.009 -0.002
Age
0.008
0.003
.007 0.002 0.013
BMI
0.007
0.003
.049
0.00004
0.013
Drinks/duy
0.014
0.012
.263 - 0.010
0.037
CignrellesAJay
-0.001
0.001
.32 -0.003 0.001
Locution*
0.041
0.037
.27 - 0.032 0.114
Entry Period**
Baseline Years Worked
0.068 -0.004
0.027 0.003
.01
0.015
0.122
.15 -0.009 0.001
'natural log Antwerp vs Decatur *1994/95 vs 1997
3M M N 02482186
1799.0024
Company Page 25 of 63
Table 5A. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Cholesterol* Change Including PPOA and the Interaction with Number of Years of Observation of Antwerp Male Employees
95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercept PFOA
4.710 ' 0.029
0.149 0.012
<.0001 .01
4.414 0.006
5.005 0.053
Years Observation PFOA x Years Obs
0.005 - 0.003
0.006 0.1X13
.36 -0.006 0.017 .20 -0.009 0.002
Age
0.009
0.003
.008 0.003, 0.016
BMI
0.008
0.<X)5
.14 -0.003 0.019
DrinksAlay
0.022
0.013
.09 -0.004 0.047
Cigaretles/day
0.0007
0.(K)2
.70 -0.003 0.004
Entry Period**
0.079
0.038
.04
0.004
0.153
Baseline Years Worked
- 0.002
0.004
.67 - 0.010 0.007
*natural log **1994/95 vs 1997
3M M N 02482187
1799.0025
Table 5B. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from 'resting Potential Determinants of Cholesterol* Change Including PFOA and the Interaction with Number of Years of Observation of Anlwerp Subgroup A (1995, 1997 and 2000) Male Employees
.y Company Page 26 of 63
95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercept
5.059
0.414
<.0001
4.194
5.925
PFOA
' 0.044
0.020
.03
0.004
0.084
Years Observation
0.037
0.015
.02
0.007
0.067
PFOA x Years Obs
-0.013
0.005
.02
- 0.023
-0.002
Age
-0.0007
0.012
.95 - 0.025 0.024
BMI
0.004
0.012
.77 - 0.020 0.028
Drinks/day
-0.016
0.019
.41 -0.054 0.023
Cigurettesfday
0.003
0.005
.51 -0.007 0.013
Baseline Years Worked
0.015
0.016
.36 -0.018
0.047
*naturul log
3M MN02482188
1799.0026
. -.I Company Page 27 o f 63
Table 5C. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Cholesterol* Change Including PPOA and the Interaction with Number of Years of Observation of Antwerp Subgroup B (1995 and 2000) Male Employees
95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercept
4.838
0.244
<0.001
4.346
5.330
PFOA
' 0.018
0.017
.30 -0.016 0.052
Years Observation
0.005
0.008
.55 -0.011
0.021
PFOA x Years Obs
- 0.002
0.004
.58 -0.009 0.005
Age
0.004
0.005
.40 -0.006 0.015
BM1
0.014
0.009
.13 -0.004 0.031
Drinks/day
0.017
0.022
.45 - 0.028 0.061
Cigarellcs/day
0.002
0.003
.44 -0.004 0.009
Baseline Years W o rk e d __
-0.0001
0.006
.99 -0.011
0.011
`natural lug
3M MN02482189
1799.0027
Table 5D. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits front 'I'esting Potential Determinants of Cholesterol* Change Including PFOA and the Interaction with Nutnlter of Years of Observation of Antwerp Subgroup C ( 1997 and 2000) Male Employees
-..*1 Company Page 28 o f 63
' ___ 95% Confidence Limits
Coefficient
SF.
p-value
Lower
Upper
Intercept
4.528
0.281
<.0001
3.955
5.100
PFOA
' 0.004
0.062
.95 -0.125 0.132
Years Observation
-0.0I0
0.026
.70 -0.065
0.044
PFOA x Years Obs
O.OIO
0.022
.65 -0.035 0.055
Age
0.0I6
0.006
.01
0.004
0.028
BMI Drinks/duy
0.009 0.033
0.012 0.032
.43 -0.015 0.033 .31 - 0.033 0.100
Cigarettes/day
- 0.0001
0.003
.97 -0.007
0.006
Baseline Years Work
- 0.005
0.008
.49 -0.021
0.011
"natural log
3M MN02482190
1799.0028
_,M Company Page 29 of 63
Table 5E. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Cholesterol* Change Including PFOA and the Interaction with Number of Years of Observation of Decatur Male Employees
95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercept
5.220
0.206
<.0001
4.810
5.630
PFOA
' 0.016
0.016
.34 -0.017 0.048
Years Observation
-0.002
0.1X18
.77 - 0.017 0.013
PFOA x Years Obs
-0.003
0.003
.22 -0.009
0.002
Age
0.002
0.005
.70 -0.008
0.012
BMI
0.003
0.004
.55 -0.006 0.011
Drinks/day
- 0.088
0.035
.01
-0.158
-0.018
Cigaretles/day
-0.002
0.001
.15 -0.004 0.0007
Entry Period**
0.047
0.040
.24 - 0.032 0.125
Baseline Years Worked
-0.002
0.004
.62 -0.010 0.006
*nalural log **1994/95 vs 1997
3M MN02482191
1799.0029
. Company Page 30 of 63
Table 6. Mixed Model Coefficient list!inales, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Cholesterol* Change Including TOP and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
- Coefficient
si;
n-value
Lower
Upper
Intercept
4.828
0.127
<.0001
4.577
5.079
TOP
' 0.021
0.008
.007 0.006 0.035
Years Observation TOP x Years Obs
0.004 ' - 0.003
0.005
o.ooi
;
.37 .07
- 0.005 -0.005
0.014 0.0003
Age
0.007
0.003
.01
0.002
0.013
BMI
0.006
0.003
.05
-0.0001
0.013
Drinks/duy
0.012
0.012
.32 -0.012 0.036
Cigareltes/duy
-0.001
0.001
.37 -0.003 0.001
Location* Entry Period4*
0.042 0.063
0.037 0.027
.26 -0.032
0.115
.02
0.010
0.117
Baseline Years Worked
-0.004
0.003
.17 -0.009 0.002
'natural log *Antwerp vs Decatur **1994/95 vs 1997
3M MN02482192
1799.0030
Table 6A. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Cholesterol" Change Including TOP and the Interaction with Number of Years of Observation of Antwerp Male Employees
. 31 uf 63
95% Confidence Limits
Coefficient
Sli
p-vulue
Lower
Upper
Intercept
4.721
0.150
< >0001
4.424
5.018
TOF
, 0.017
0.011
.12 -0.004 0.038
Years Observation
0.004
0.007
.55 -0.009 0.017
TOF x Years Obs
-0.0008
0.002
.70 -0.005 0.003
Age
0.009
0.003
.01
0.002
0.016
BMI
0.009
0.006
.12 -0.002 0.020
Drinks/day
0.019
0.013
.14 -0.006 0.045
Cigarelles/day
0.0008
0.002
.69 -0.003
0.005
Entry Period**
0.070
0.038
.07 -0.006 0.145
Baseline Years Worked
- 0.0008
0.004
.85 -0.009 0.008
"natural lug **1994/95 vs 1997
3M MN02482193
1799.0031
Table 6B. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Cholesterol* Change Including TOP and the Interaction with Number of Years of Observation of Decatur Male Employees
,, .A Company Page 32 of 63
___ 95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercept
5.214
0.202
<.0001
4.811
5.616
TOP
0.014
0.011
.19 -0.007 0.035
Years Observation
-0.002
0.008
.79 -0.018
0.013
TOFx Years Obs Age BMI Drinks/day Cigarelles/day
-0.002 0.002 0.002
-0.090 -0.002
0.002 0.005 0.004 0.035 0.001
t
.22 .69 .55 .012 .161
-0.006 -0.008 -0.006 -0.160 -0.004
0.001 0.012 0.011 - 0.020 0.0007
Baseline Years Worked
-0.002
0.004
.60 -0.010
0.006
*naturul log **1994/95 vs 1997
3M MN02482194
1799.0032
a Company Page 33 o f 63
Table 7. Mixed Model Cocfllcicnl Estimates, Standard Errors (SB), P-Values and 95% Confidence Limits from Testing Potential Determinants of IIDL* Change Including PPOS and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
Coefficient
Sli :
p-value
Lower
Upper
Intercept PFOS
4.212 ' - 0.010
0.144 0.008
<.0001 .24
3.930 - 0.026
4.495 0.007
Years Observation
0.002
0.005
.71 -0.008 0.012
PFOS x Years Ohs
-0.001
0.002
.52 -0.005 0.002
Age
0.004
0.003
.22 , - 0.002
0.011
BMI
-0.017
0.(X)4
<.0001
- 0.025
0.010
Drinks/day
0.064
0.013
<.0001
0.037
0.090
Cigarcltcs/day
- 0.004
0.001
,
.0005
- 0.007
- 0.002
Location*
0.006
0.043
.89 - 0.079 0.091
Entry Period**
Baseline Years Worked
0.025 -0.007
0.032 0.003
. 44
.03
- 0.038 -0.013
0.088 -o.ooos
'natural log Antwerp vs Decatur *1994/95 vs 1997
3M MN02482195
1799.0033
.-- v
. Company Page 34 of 63
Table 8. Mixed Model Coefficient Listimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of HDL* Change Including PFOA and the Interaction with Numlter of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercepl
4.216
0.145
<.0001
3.929
4.503
PPOA
' - 0.006
0.011
.56 - 0.027 0.015
Years Observation
0.005
0.005
.35 - 0.005 0.014
PPOA x Years Ohs
- 0.002
0.(X)2
.40 -0.006 0.002
Age
0.004
0.003
.28 ' - 0.003
0.010
BMI
-0.017
0.004
<.0001
- 0.024
- 0.010
Drinks/day
0.062
0.013
<.0001
0.036
0.088
Cigareltcs/day
- 0.004
0.001
:.
.0004
- 0.007
- 0.002
Location*
0.008
0.043
.85 - 0.076 0.093
Entry Period**
0.020
0.032
.53 -0.042 0.082
Baseline Years Worked
-0.007
0.003
.04
- 0.013
-0.0004
'natural log Antwerp vs Decatur *1994/95 vs 1997
. -
3M MN02482196
1799.0034
.Company Page 35 of 63
Table 9. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of HDL* Change Including TOP and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
Coefficient
Sli
p-value
Lower
Upper
Intercept TOP
4.217 0.006
0.145 0.008
;
<.0001 .44
3.931 - 0.023
4.502 0.010
Years Observation TOP x Yearn Ob*
0.004 - 0.0009
0.005 0.001
.47 -0.007 .57 -0.004
0.014 0.002
Age
0.004
0.003
.25 -0.003 0.010
BMI
-0.017
0.004
<.0001
- 0.025
-0.010
Drinks/day
0.063
0.013
<.0001
0.037
0.089
Cigarelles/duy
-0.004
0.001
.0005
-0.007
-0.002
Location*
0.007
0.043
.88 - 0.078 0.092
Entry Period**
0.021
0.032
.50 . -0.041
0.084
Baseline Years Worked
- 0.007
0.003
.04
-0.013
-0.0004
'natural log Antwerp vs Decatur 1994/95 vs 1997
3M MN02482197
1799.0035
1 Company Page 36 o f 63
Table 10. Mixed Model Coefficient estimates, Standard Errors (SE). P-Values and 95% Confidence Limits from Testing Potential Determinants of Triglyceride' Change Including PFOS and the Interaction with Niunltcr of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
Coefficient
Sli
p-valuc
Lower
Upper
Intercept
2.7.10
0.335
< '.0001
2.068
3.392
PFOS
0.025
0.020
.22 -0.015 0.065
Years Observation
- 0.004
0.013
.73 - 0.029 0.021
PFOS x Years Obs
0.006
0.005
.22 -0.004 0.015
Age
0.003
0.008
.67 -0.011
0.018
BMI
0.006
0.009
< 0001
0.048
0.083
Drinks/day
- 0.029
0.033
.37 - 0.094 0.035
Cigarettes/duy
0.011
0.003
.0002
0.005
0.017
Location*
0.052
0.099
.60 -0.143
0.247
Paltry 1`uriod**
0.089
0.07.3
.22 -0.055 0.234
Baseline Years Worked
0.005
0.007
.50 -0.010 0.019
'natural log Antwerp vs Decatur **1994/95 vs 1997
3M MN02482198
1799.0036
Table 11. Mixed Model Coefficient Estimates, Standard Grrors (SE), P-Values and 95% Confidence Limits front Testing Potential Determinants ofTriglyceride" Change Including PFOA and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
I Lumpaiiy i-age 37 of 63
95% Confidence Limits
Coefficient
Sli
p-value
Lower
Upper
Intercept PFOA
2.539 . 0.094
0.332 0.025
<.0001 .0002
1.883 0.045
3.196 0.144
Years Observation
0.IXI7
0.012
.57 -0.017 0.031
PFOA x Years Obs
-0.008
0.005
.12 -0.018 0.002
Age
0.006
0.007
,
.42
-0.009
0.021
BMI
0.066
0.009
<.0001
0.049
0.083
Drinks/day Cigarettes/day
-0.027 0.011
0.032 0.003
.40 .0002
-0.090 0.005
0.037 0.017
Location*
0.072
0.096
.46 -0.118 0.262
Entry Period**
Baseline Yeurs Worked
0.098 0.003
0.070
0.007
.17 -0.041
0.236
.67 - 0.011 0.017
"natural lug
Alllmii y* I I f!:iiiiii
u 1IM*)5 vs l!HW
3M MN02482199
1799.0037
.,M Company Page 38 or 63
Table 11A. Mixed Model Coefficient Estimates,'Standard Errors (SE), P-Values and 95% Confidence Limits rrom Testing Potential Determinants of Triglyceride* Change Including PPOA and the Interaction with Number of Years of Observation of Antwerp Male Employees
95% Confidence Limits_________
Coefficient
SE
p-value
Lower
Upper
Intercept
3.067
0.394
< 0001
2.286
3.848
PFOA
' 0.089
0.030
.005 0.028 0.149
Years Observation
0.024
0.015
.12 -0.006 0.053
PFOA x Years Obs
- 0.010
0.007
.15 - 0.023 0.004
Age
0.012
0.009
.22 -0.007 0.030
BMI
0.039
0.014
.007 0.011 0.068
DrinksAJay
- 0.026
0.033
.44 -0.092
0.040
CigurettexVduy
0.018
0.005
.0004
0.008
0.028
Entry Period**
0.013
0.100
.90 - 0.212 0.186
Baseline Years Worked
0.003
0.011
.76 - 0.019 0.026
'natural log **1994/95 vs 1997
''
3M MN02482200
1799.0038
Company Page 39 o f 63
Table I Hi. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Triglyceride* Change Including PFOA and the Interaction with Number of Years of Observation of Antwerp Subgroup A (1995, 1997 and 2000) Male Employees
95% Confidence Limits
Coefficient
SE
p-vulue
Lower
Upper
Intercept
3.104
1.063
.009 0.880 5.328
PFOA
' 0.182
0.051
.001 0.079 0.286
Years Observation
0.167
0.037
<.0001
0.091
0.241
PFOA x Years Obs
-0.061
0.011
<.0001
- 0.084
- 0.039
Age
- 0.007
0.031
.83 -0.069 0.056
BMI
0.039
0.030
.20 - 0.021 0.100
Drinks/day
- 0.082
0.051
.12 -0.186
0.023
Cigarettes/day
0.008
0.012
.52 - 0.017 0.033
Baseline Years W orked__
0.036
0.041
.40 -0.049 0.120
"natural log
3M MN02482201
1799.0039
.1 Company 1'ajje 4 0 o f 63
Table 11C. Mixed Model CoelTicieni Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits
from Testing Potential Determinants of Triglyceride* Change Including PFOA and the Interaction with
Number or Years of Observation of Antwerp Subgroup D (1995 and 2000) Male Employees
.
95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercept
2.775
0.523
<i .0001
1.720
3.830
PFOA
0.097
0.038
.02
0.019
0.174
Years Observation
0.005
0.018
.80 - 0.033 0.042
PFOA x Years Obs
0.0008
0.009
.93 -0.017
0.018
Age
0.019
0.011
.10 -0.004 0.041
BM1
0.042
0.019
.04
0.003
0.081
Drinks/day
0.038
0.050
.45 -0.062 0.138
Cigarettes/day
0.022
0.007
.003 0.008 0.036
Baseline Years Worked
- 0.002
0.012
.83 -0.026 0.021
'natural log
3M MN02482202
1799.0040
ivl Company Page 4 1 o f 63
Table I ID. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Triglyceride11Change Including PFOA and the Interaction with Numlter of Years of Observation of Antwerp Subgroup C (1997 and 2000) Male Employees
95% Confidence Limits
Coefficient
SE
p-vulue
Lower
Upper
Intercept
3.285
0.744
'.0001
1.769
4.801
PFOA
' 0.032
0.149
.83 .
- 0.280
0.344
Years Observation
- 0.072
0.063
.26 - 0.203 0.058
PFOA x Years Obs
0.020
0.051
.70 - 0.087 0.128
Age
- 0.005
0.016
.77 - 0.038 0.028
BMI
0.057
0.030
.08 -0.006 0.120
Drinks/day
- 0.025
0.081
.76
0.195
0.145
Cigaretles/day
0.019
0.008
.032 0.002 0.036
Baseline Years Worked__
0.010
0.021
.65 - 0.034 0.053
'natural log
3M MN02482203
1799.0041
.*1 Company Page 42 o f 63
Table I Hi. Mixed Model Coeffideni Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Triglyceride* Change Including PFOA and the Interaction with Number of Years of Observation of Decatur Male Employees
95% Confidence Limits
Coefficient
SI!
p-value
Lower
Upper
Intercept PFOA
2.581 ` 0.054
0.567 0.046
<.0001 .24
1.450 - 0.037
3.712 0.145
Years Observation PFOA x Years Obs Age
-0.028 0.002
-0.0008
0.022 0.008 0.013
.20 . -0.071 .85 -0.014 .95 - 0.028
0.015 0.017 0.026
BMI Drinks/day Cigarettes/day
0.073 - 0.038
0.005
0.012 0.099 0.004
;
}
<.0001 .70 .16
0.050 -0.235 -0.002
0.096 0.158 0.012
Entry Period**
0.274
0.109
.01
0.058
0.491
Baseline Years Worked
0.009
0.011
.44 -0.013 0.030
"natural log **1994/95 vs 1997
3M MN02482204
1799.0042
A Company Page 43 o f 63
Tuhle 12. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits front Testing Potential Determinants of Triglyceride* Change Including TOP and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
________95% Confidence Limits
Coefficient
SE !
p-value
Lower
Upper
Intercept
2.612
0.334
<.0001
1.953
3.272
TOP
' 0.053
0.020
.008 0.014 0.093
Years Observation
- 0.0005
0.013
.97 -0.027 0.026
TOF x Years Obs
-0.0005
0.004
.91 -0.008 0.007
Age
0.004
.
0.007
.57 -0.010 0.019
BMI
0.066
0.009
<.0001
0.049
0.084
Drinks/day
-0.031
0.032
.34 -0.095
0.033
Cigarelles/day
0.011
0.003
.0002
0.005
0.017
Location*
0.074
0.098
.45 -0.119 0.266
Entry Period**
Baseline Years Worked
0.0U5 0.004
0.071 0.007
.23 - 0.055 0.226 .58 - 0.010 0.018
"natural log Antwerp vs Decatur *1994/95 vs 1997
3M MN02482205
1799.0043
A Company
Page 44 iif 63
Table 12A. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Vulues and 95% Confidence Limits from Testing Potential Determinants of Triglyceride* Change Including TOP and the Interaction with Number of Years of Observation for Antwerp Male Employees
__________ 95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercept
3.078
0.395
<.0001
2.294
3.862
TOP
' 0.053
0.028
.06 -0.002
0.107
Years Observation
0.016
0.017
.35 -0.018
0.049
TOP x Years Obs
-0.0007
0.006
.90 - 0.012
0.010
Age
0.009
0.009
.32 -0.009
0.028
BMI
0.042
0.014
0.004
0.014
0.071
Drinks/duy
- 0.032
0.034
.34 -0.099
0.035
Cigareltes/day
0.018
0.005
.0005
0.008
0.029
Entry Period**
-0.045
0.101
.66 - 0.245 0.155
Baseline Years Worked
0.007
0.0 II
.56 - 0.016 0.029
*naturul log **1994/95 vs 1997
3M MN02482206
1799.0044
A Company Page 45 o f 63
Table 12B. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Triglyceride* Change Including TOP and the Interaction with Number of Years,of Observation for Decatur Male Employees
95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercept
2.644
0.563
<.0001
1.521
3.766
TOF
' 0.031
0.030
.29 - 0.028 0.090
Years Observation
-0.035
0.022
.12- -0.079
0.009
TOF x Years Obs
0.004
0.005
.45 -0.007 0.015
Age
-0.002
0.014 '
.90
- 0.029
0.025
BMI
0.073
0.012
<.0001
0.050
0.010
Drinks/dny
-0.030
0.099
.76 - 0.227 0.166
Cigareltes/day
0.005
0.004
.20 -0.003 0.012
Entry Period**
Buscline Years Worked
0.275 0.009
0.111 0.011
.01
0.055
0.494
.44 -0.013 0.030
"natural log **1994/95 vs 1997
3M MN02482207
1799.0045
>1Company 'age 46 o f 63
Tabic 13. Mixed Model Coefficient Estimates, Standard Errors (SE). P-Values and 95% Confidence Limits from Testing Potential Determinants of Alkaline Phosphatase* Change Including PFOS and the Interaction with
Number of Years of Observation of Antwcip and Decatur Male Employees
95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercept
3.789
0.176
<.0001
3.442
4.137
PFOS
' 0.002
0.009
.87 -0.017 0.020
Years Observation
-0.051
0.006
< .0001
-0.062
- 0.040
PFOS x Years Obs
0.002
0.002
.47 -0.003 0.006
Age
0.005
0.004
.20 -0.003 0.012
BMI
-0.0007
0.004
.88 -0.009
0.008
Drinks/day
-0.001
0.014
.94 -0.030
0.028
Cigarettes/day
0.003
0.001
.03
0.0004
0.006
Location*
- 0.242
0,049
<.0001
-0.338
-0.145
Entry Period**
0.098
0.037
.008 0.025 0.171
Baseline Years Worked
-0.006
0.004
.10 -0.013 0.001
Triglycerides*
0.113
0.024 :
<.0001 , 0.067
0.160
"natural log Antwerp vs Decutur ** I994/`J5 vs 1997
3M MN02482208
1799.0046
(
, impaiiy Pugc ,7of 63
I'ablc 14. Mixed Model Coefficient Estimates, Standard Errors (SB), P-Values and 95% Confidence Limits frotn Testing Potential Determinants of Alkaline Phosphatase* Change Including PFOA and the Interaction with
Number of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
Coefficient
SII
p-value
Lower
Upper
Intercept
3.785
0.176
<.0001
3.437
4.133
PFOA
0.005
0.012
.69 - 0.019 0.028
Years Observation
-0.047
0.006
<.0001
- 0.058
-0.036
PFOA x Years Obs
-0.001
0.002
.62 -0.005
0.003
Age
0.005
0.004
.19 -0.002 0.013
BMI
-0.0009
0.004
.85 -0.010 0.008
Drinks/day
- 0.002
0.015
.89 -0.031
0.027
Cigarelles/duy
0.003
0.001
.03
0.0004
0.006
Location*
- 0.243
0,049 ,
<.0001
-0.340
-0.147
Entry Period**
0.100
0.036
.007 0.028 0.172
Baseline Years Worked
- 0.006
0.004
.09 - 0.014 0.001
Triglycerides*
0.114
0.024
<.0001
0.066
0.161
'natural log Antwerp vs Decatur **1994/95 vs 1997
3M MN02482209
1799.0047
I Company l-ajje 48 o f 63
Table 15. Mixed Model Coefficient lisliimnes, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Alkaline Phosphatase* Change Including TOF and the Interaction with
Number of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
Coefficient
SF.
p-value
Lower
Upper
Intercept
3.789
0.177
<.0001
3.441
4.138
TOP
-0.00004
0.009
.99 -0.019 0.018
Years Observation
- 0.049
0.1X16
<.(1001
-0.060
- 0.037
TOF x Years Obs
-0.00006
0.0017
.97 -0.003
0.003
Age
0.005
0.1X14
.19 -0.003 0.012
BMI
-0.001
0.004
.82 - 0.010 0.008
Drinks/duy
- 0.002
0.015
.91 -0.031 0.028
Cigarettes/day
0.003
0.001
.03
0.0004
0.006
Location*
- 0.245
0.049
<.0001
- 0.342
-0.148
Entry Period**
Baseline Years Worked
0.100 -0.006
0.036 0.004
.007 0.028
to - 0.013
0.172 0.001
Triglycerides'
0.115
0.024
<.0001
. 0.068
0.162
'natural log Antwerp vs Decatur *1994/95 vs 1997
' .
3M MN02482210
1799.0048
( Company rage 49 of 63
Table 16. Mixed Model Coefficient ItKlimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of GGT* Change Including PFOS and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercept
1.883
0.373
<.0001
1.146
2.620
PFOS
- 0.004
0.020
.84 -0.043 0.035
Years Observation
- 0.075
0.012
<.0001
-0.098
-0.051
PFOS x Years Obs
0.004
0.004
.42 -0.005 0.012
Age
- 0.003
0.<H)8
.74 -0.019 0.013
BM1
0.005
0.009
.59 -0.013
0.024
Drinks/day
0.042
0.031
.18 -0.020 0.104
Cigaretles/day
- 0.0009
0.003
.77 -0.007 0.005
Locution*
-0.096
0.104
.36 - 0.030
0.110
Entry Period**
0.358
0.078
<.0001
0.204
0.512
Baseline Years Worked
0.008
0.007
.30 -0.007 0.024
Triglycerides1'
0.251
0.050
<.0001
0.152
0.350
'natural log Antwerp vs Decatur **1994/95 vs 1997
3M MN02482211
1799.0049
Table 17. Mixed Model Cocfficienl Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of OGT* Change Including PFOA and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
M Company Page SOof 63
______ 95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercept
1.876
0.374
<.0001
1.138
2.613
PFOA
' -0.009
0.025
.72 - 0.058 0.040
Years Observation
- 0.077
0.012
<.0001
-0.100
- 0.054
PFOA x Years Ohs
0.005
0.005
.29 -0.004 0.014
Age
- 0.002
0.008
.76 -0.018 0.013
BMI
0.004
0.009
.64 - 0.014 0.023
Drinks/day
0.043
0.031
.17 -0.019 0.105
Cigareltes/day
-0.0007
0.003
.82 -0.007 0.005
Location*
- 0.097
0.104
.35 - 0.301 0.108
Entry Period**
0.355
0.077
<.0001
0.203
0.507
Baseline Years Worked
0.008
0.008
.30 -0.007 0.024
Triglycerides*
0.256
0.051
<.0001
0.156
0.356
"natural log Antwerp vs Decatur **1994/95 vs 1997
. 3M MN02482212
1799.0050
M Company Page 51 o f 63
Table 18. Mixed Model Coefficient lislimales, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of GGT* Change Including TOP and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercept
1.870
0.374
< 0001
1.132
2.608
TOF
' 0.002
0.020
.93 -0.037 0.041
Years Observation
- 0.079
0.013
< .0001
-0.104
- 0.054
TOF x Years Obs
0.004
0.003
.25 -0.003 0.011
Age
-0.003
0.008
.75 -0.018 0.013
BMI
0.005
0.009
.57 -0.013 0.024
Drinks/day
0.043
0.031
.17 -0.019 0.104 .
Cigareltes/day
-0.0009
0.003
.77 -0.007 0.005
Location*
- 0.088
0.104
.40 -0.294 0.117
Entry Period**
0.352
0.078
< .0001
0.200
0.505
Baseline Years Worked
0.008
0.008
.31 -0.007 0.024
Triglycerides'
0.249
0.050
< 0001
0.149
0.348
'natural log Antwerp vs Decatur 1994/95 vs 1997
3M MN02482213
1799.0051
M Company Page 52 of 63
Table 19. Mined Model Coefficient Estimates, Standard Errors (SB), P-Values and 95% Confidence Limits from Testing Potential Determinants of AST* Change Including PFOS and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
Coefficient
SB
p-value
Lower
Upper
Intercept
3.080
0.198
< 0001
2.689
3.471
PFOS
' 0.010
0.011
.39 - 0.013 0.032
Years Observation
- 0.009
0.007
.19 -0.024 0.005
PFOS x Years Obs
0.0007
0.003
.79 -0.005 0.006
Age
- 0.008
0.004
.05
-0.016
-0.00005
BMI
0.004
0.005
.47 -0.007
0.014
Drinks/duy
0.030
0.018
.11 -0.007 0.066
Cigarctlcs/day
- 0.003
0.002
.07 -0.006 0.0002
Location*
0.102
0.053
.06 -0.206 0.003
Entry Period**
0.039
0.039
.32 - 0.038 0.116
Baseline Years Worked
0.005
0.004
.22 -0.003 0.012
Triglycerides*
0.063
0.029
.03
0.005
0.121
'natural log Antwerp vs Decatur **1994/95 vs 1997
3M MN02482214
1799.0052
M Company Page 53 o f 63
Table 20. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from 'I'esling Potential Determinants of AST* Change Including PFOA and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
Coefficient
Sli
p-value
Lower
Unner
Intercept PFOA
2.053 ' 0.027
0 .199 0.015
< .0001 .06
2.661 -0.002
3.445 0.056
Years Observation PFOA x Years Obs Age
- 0.008 - 0.002 - 0.007
0.007 0.003 0.004
.28 - 0.022 0.006 .41 -0.008 0.003 .08 -0.015 0.0008
BMI
0.004
0.005
.39 -0.006 0.015
Drinks/day
0.030
0.018
.10 -0.006
0.066
Cigarcltcs/day
Location*
Entry Period**
Baseline Years Worked
-0.003 - 0.097
0.044 0.004
0.002 0.053 0.039 0.004
.07 -0.006
0.0002
.07 -0.201
0.008
.26 - 0.032 0.120
.27 -0.003 0.012
Triglycerides*
0.054
0.030
.07 -0.004 0.113
*natural log Antwerp vs Decatur 1994/95 vs 1997
3M MN02482215
1799.0053
H Company Page 54 o f 63
Table 2 1. Mixed Model Coefficient l-'stimates. Standard Errors (SE), P-Values and 95% Confidence Limits: from Testing Potential Determinants of AST* Change Including TOF and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
'
__________ 95% Confidence Limits
Coefficient
Sli
p-value
Lower
Upper
Intercept
3.058
0.198 ,
< .0001
2.666
3.449
TOF
0.018
0.011
.12 -0.005
0.04
Years Observation
-0.009
0.008
.24 - 0.024 0.006
TOF x Years Obs
-0.006
0.002
.79 -0.005 0.004
Age -0.008
0.004
.06 -0.016
0.0002
BM1
0.004
0.005
.40 -0.006
0.015
Drinks/duy
0.029
0.018
.12 -0.007
0.065
Cigarettes/day
- 0.003
0.002
.07 -0.006 0.0002
Location*
-0.095
0.053
.08 -0.199 0.010
Entry Period**
0.039
0.039
.31 - 0.037 0.115
Baseline Years Worked
0.005
0.004
.24 -0.003
0.012
Triglycerides'
. 0.058
0.029
.05
0.00003
0.116
*natural log Antwerp vs Decatur 1994/95 vs 1997
3M MN02482216
1799.0054
* Company 4 c 55 ol <>i
Table 22. Mixed Model Coefficient listimutes. Standard Errors (SE), P-Valuesand 95% Confidence Limits from Testing Potential Determinants of ALT* Change Including PFOS and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
Intercept PFOS
Coefficient 2.501
' 0.010
Sii 0.273 0.016
p-value <.0001
.54
Lower 1.961 -0.021
Upper 3.041 0.041
Years Observation PFOS x Years Obs Age
- 0.095 - 0.00(K)3
0.0009
0.010 0.004 0.006
<.0001 .99 .88
-0.115 -0.008 -0.012
- 0.075 0.008 0.010
BMI
0.010
0.007
.17 -0.004 0.024
Drinks/day
-0.012
0.025
.63 -0.062 0.038
Cigareiles/day Location*
-0.008 -0.088
0.002 0.073
.001 -0.012 -0.003
.23 -0.233
0.056
Entry Period**
Baseline Years Worked
0.329 0.001
0.054 0.005
<.0001 .84
0.222 - 0.010
0.436 0.012
Triglycerides*
0.159
0.040
.0001
0.079
0.238
`natural log Antwerp vs Decatur **1994/95 vs 1997
3M MN02482217
1799.0055
. Compiiny i\jg e5 6 of 63
Table 23. Mixed Model Coefficient estimates, Standard Errors (SE), P-Values and 95% Confidence Limits front Testing Potential Determinants of ALT* Change Including PFOA and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
95% Confidence Limits
( 'ucfficiciit
SE
r>-value
Lower
Upper
Intercept
2.479
0.272
< .0001
1.942
3.016
PEOA
0015
0.020
.46 - 0.025 0.1)54
Years Observation
-0.107
0.010
<.0001
. -0.126
- 0.087
PFOA x Years Obs
0.005
0.004
.19 -0.003 0.013
Age
- 0.0001
0.006
.98 - 0.011 0.011
BM1
0.011
0.007 :
.13
-0.003
0.025
Drinks/day
-0.009
0.025
.72 - 0.058 0.040
Cigareties/day
-0.007
0.002
.001 -0.012 - 0.003
Location*
-0.079
0.072
.28 - 0.222 0.064
Entry Period**
0.330
0.053
.<.0001
0.225
0.434
Baseline Years Worked
0.0008
0.005
.89 - 0.010 0.0 II
Triglycerides*
0.151
0.041
.0003
0.071
0.231
'natural log Antwerp vs Decatur ** 1994/95 vs 1997
3M MN02482218
1799.0056
1Company age 57 of 63
Table 24. Mixed Model Coefficient Estimates, Standard Ilnurs (SE). P-Values and 95% Confidence Limits from Testing Potential Determinants of ALT* Change Including TOP and the Interaction with Number of Years of Observation of Antwerp and Decatur Male Employees
.
. 95% Confidence Limits
Coefficient
.Sli i
p-value
Lower
Upper
Intercept
2.476
0.273
<i .0001
1.936
3.015
TOE
' 0.020
0.016 :
.21
- 0.011
0.051
Years Observation
-0.102
0.011
<.0001
-0.123
- 0.082
TOP x Years Obs
0.002
0.003
.50 -0.004 0.008
Age
- 0.0005
0.006
.93 - 0.011 0.010
BMI
0.011
0.007
.11 -0.003 0.026
Drinks/day
- 0.013
0.025
.62 -0.062 0.037
Cigarettcs/duy
-0.008
0.002
.001 -0.012 -0.003
Location*
- 0.073
0.073
.32 -0.217
0.072
Entry Period**
0.325
0.053
<.0001
0.220
0.430
Baseline Years Worked
0.0008
0.005
.88 -0.010 0.011
Triglycerides'
0.148
0.040
.0003
0.069
0.228
'natural log Antwerp vs Decatur *1994/95 vs 1997
3M MN02482219
1799.0057
Cuinpany rage 58 of 63
Table 25. Mixed Model Coefficient l.istimates. Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Total Bilirubin* Change Including PFOS and the Interaction with Number of Years o f Observation o f Antwerp and Decatur Male Employees
95% Confidence Limits
Intercept
Coefficient - 0.134
Slit 0.241
p-vulue .17
Lower -0.811
Upper 0.142
pros Years Observation PFOS x Years Obs Age BMI Drinks/duy Cigarelles/duy Location* Entry Period** Baseline Years Worked Triglycerides*
-0.018 0.033
- 0.002 0.011
-0.003 0.016
-0.008 0.315
-0.114 - 0.002
-0.088
0.014
.22
0.009
- .0005
. 0.004
.94
0.005
.02
0.007
.67
0.024
.50
0.002
<.0001
0.064
< .0001
0.047
.02
0.005 .
.64
0.037
.02
-0.046 0.0148
-0.007 0.001
-0.016 - 0.030 . -0.012
0.189 -0.206 - 0.011
-0.161
0.011 0.052 0.007 0.020 0.010 0.062 -0.004 0.441 - 0.022 0.007
-0.015
*natural log Antwerp vs Decatur **1994/95 vs 1997
3M MN02482220
1799.0058
H Company 'age 39 o f 63
Table 26. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Valucs and 95% Confidence Limits from 'I'esling Potential Determinants o f Total Bilirubin* Change Including PPOA and the Interaction with Number of Years o f Observation o f Antwerp and Decatur Male Employees
95% Confidence Limits
Intercept PFOA Years Observation PFOA x Yearn Obs Age BMI
Coefficient -0.315 ' -0.030
0.028 0.005 0.010 -0.003
Sli 0.242 0.019 0.009 0.004 0.005 0.007
p-valtie .19 .16 .003 .18 .04 .61
Lower - 0.793 ' 0.066
0.001 -0.002
0.0007 - 0.016
Upper 0.162 0.007 0.046 0.013 0.020 0.010
Drinks/day
Cigatettes/day
Location*
Entry Period** Baseline Years Worked
0.014 - 0.008
0.318 -0.124 -0.002
0.023 0.002 0.064 0.046 0.005
.55 <.0001 <.0001
.007 .71
-0.032 -0.013
0.193 -0.215 - 0.011
0.060 -0.004
0.444 - 0.034
0.007
Triglycerides*
- 0.082
0.037
.03
-0.156
-0.008
` natural log Antwerp vs Decatur **1994/95 vs 1997
3M MN02482221
1799.0059
: Company ruge 60 o f 63
Table 27. Mixed Model Coefficient Estimates, Standard Errors (SB), P-Values and 95% Confidence Limits from Testing Potential Determinants o f Total Bilirubin* Change Including TOP and the Interaction with Number of Years o f Observation o f Antwerp and Decatur Male Employees
95% Confidence Limits
Coefficient
Sit
p-vulue
Lower
Uniter
Intercept
-0.318
0.242
.19 - 0.796 0.160
TOP
' -0.020
0.014
.16 -0.049 0.008
Years Observation
0.029
0.010
.005 0.009 0.049
TOP x Years Ohs
0.003
0.003
.36 - 0.003 0.009
Age
0.011
0.005
.03
0.001
0.020
BM1
-0.003
0.007
.65 - 0.016 0.010
Drinks/day
0.016
0.023
.51 -0.031 0.062
Cigaretlcs/day
-0.008
0.002
<.0001
- 0.012
-0.004
Location4
0,316
0.064
<.0001
0.190
0.442
Entry Period**
0.120
0046
.01
-0.210
- 0.029
Baseline Years Worked
- 0.002
0.005
.68 -0.011
0.007
Triglycerides*
-0.085
0.037
.02
-0.158
-0.012
'natural log *Anlwerp vs Decatur
**1994/95 vs 1997
3M MN02482222
1799.0060
i Company Page 61 of 03
'Fable 28. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants o f Direct Bilirubin* Change Including PFOS and the Interaction with
Number of Years o f Observation o f Antwerp ttnd Decatur Male Employees
95% Confidence Limits
Intercept PFOS
Coefficient - 1.756 ' -0.013
SE 0.204 0.013
p-value . <.0001
.29
Lower -2.160 -0.039
Upper
- 1.355
0.012
Years Observation PFOS x Years Obs Age BMI Drinks/duy Cigaretles/day Location* Entry Period** Baseline Yeats Worked
- 0.097 -0.006
0.007 -0.003
0.018 -0.0005
0.076 0.353
- 0.001
0.009 0004 0.004 0.006 0.020 0.002 0.053 0.038 0.004
} ,
<.0001 .18 .06 .58 .37 .79 .15
. <.0001 .74
-0.116 - 0.014 ' - 0.0003 -0.015 - 0.022 -0.004 - 0.028
0.277 -0.009
- 0.079 0.003 0.015 0.008 0.058 0.003 0.180 0.428 0.006
Triglycerides*
-0.090
0033
.006 -0.155 - 0.026
'natural log
Antwerp vs Decatur 1994/95 vs 1997
3M MN02482223
1799.0061
Table 29. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Direct Bilirubin* Change Including PPOA and the Interaction with
Number of Years o f Observation o f Antwerp und Decatur Male Employees
95% Confidence Limits
Coefficient
SE
p-value
Lower
Upper
Intercept PFOA
- 1.753 - 0.012
0.207 0.017
.
<.0001 .47
-2.161 -0.045
- 1.345 0.021
Years Observation
' - 0.095
0.009
< .0001
-0.113
- 0.077
PFOA x Years Obs Age
-0.004 0.006
0.004 0.004
.27 -0.012 0.003 .11 -0.001 0.014
BMI
- 0.003
0.006
.66 -0.014 0.009
Drinks/day
0.014
0.020
.50 -0.026 0.053
Cigareltes/day
-0.0005
0.002
.80 -0.004 0.003
Locution'"
0.083
0.053
.12 -0.022 0.188
Entry Period**
0.345
0.038
<.0001
0.271
0.420
Baseline Years Worked
-0.0008
0.004
.83 -0.008 0.007
Triglycerides*
- 0.089
0.033
.009 -0.155 - 0.023
Natural lug Antwerp vs Decatur **1994/95 vs 1997
.
3M MN02482224
1799.0062
i -1 Company Page 63 of 63
Table 30. Mixed Model Coefficient Estimates, Standard Errors (SE), P-Values and 95% Confidence Limits from Testing Potential Determinants of Direct Bilirubin* Change Including TOE and the Interaction with Number of Years o f Observation o f Antwerp and Decatur M ale Employees
95% Confidence Limits
Intercept TOF Years Observation TO F x Years Obs Age BMI Drinks/day Cigureiles/duy Location* Entry Period** Baseline Years Worked Triglycerides*
Coefficient - 1.748 -0.013 - 0.093 - 0.004
0.007 -0.003
0.017 -0.0004
0.074 0.349 -0.001
- 0.087
SE 0.205 0.013 0.010 0.003 0.004 0.006 0.020 0.002 0.053 0.038 0.004
'
0.033
p-value <.0001
.33 <.0001
.21 .08 .57 .39 .84 .16 <.0001 .77
.009
Lower -2.154 -0.038 -0.113 -0.011 -0.0008 -0.015 -0.022 ' -0.004 -0.031
0.274 -0.008
-0.152
Upper - 1.343
0.013 - 0.073
0.002 0.014 0.008 0.057 0.003 0.179 0.424 0.006
- 0.022
` natural log Antwerp vs Decatur 1994/95 vs 1997
3M MN02482225
1799.0063