Document DdXvnJqQbQyrRBB1mzox2JDgB
FINAL REPORT Epidem iology, 220-3W -05
M edical Departm ent 3M Company
St. Paul. M N 55144
Date: June 25, 2001
Title: Identification of Fluorochemicals in Human Tissue
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Study Start Date: March 22, 1999
Estimated Date of Final Report: June 15, 2001
Protocol Number EPI-0018 IRB Approval
Exempt Expedited X
IRB Approval Date: 3M IRB March 10, 1999 HAM Approval March 22, 1999
Principal Investigator: Co-investigators:
Geary W. Olsen, DVM, Ph.D.1
Kristen J. Hansen, Ph.D.2 Lisa A. Clemen, MS2 Jean M. Burris, MPH, RN1 Jeffrey H. Mandel, MD, MPH
Study Director:
Jeffrey H. Mandel, MD, MPH
1. 3M Company, Medical Department, Building 220-3W-05, St. Paul, MN 55144 2. 3M Company, Environmental Laboratory, Building 220-2E-09, St. Paul, MN 55133
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ABSTRACT
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Analytical methods have recently been developed, using high performance liquid
chromatography/electrospray tandem mass spectrometry (HPLC-ESMSMS), that can be
used to measure specific perfluoroinated chemicals in serum and liver samples. A
recently completed six-month feeding study of perfluorooctanesulfonate (PFOS,
CgFnSOs') to cynomolgus monkeys reported liver to serum ratios at end of study that
were approximately 1:1 in the low- (0.03 mg/kg/day) and mid- (0.15 mg/kg/day) dose
groups. A non-linear response with a plateau in serum levels was reported for the high
dose group (0.75 mg/kg/day). These primate data suggested that serum PFOS levels may
serve as an adequate marker of liver burden at levels less than 100 ppm (parts per million,
ug/mL). The purpose of this investigation was to determine whether the 1:1 liver to
serum ratio reported in this primate study was mirrored in PFOS levels measured in non
occupationally exposed humans. Average serum levels (30 ng/mL) in humans have been
measured at levels slightly less than three orders of magnitude lower than the average
low-dose group serum PFOS level (20 ug/mL) in the primate study.
For the present study, all human sera and liver donor tissue were obtained through
the International Institute for the Advancement of Medicine (HAM). HAM is a non
profit organization whose purpose is to facilitate the placement of non-transplantable
human organs and tissues for biomedical research and education. Upon acceptable donor
qualifications, HAM obtained 5 ml of blood and 10 grams of liver and then froze the
samples until shipment to the 3M Medical Department. A total of 31 donor samples were
obtained over an 18 month time period.
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All samples were analyzed for quantitative determination of four
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perfluorochemicals: PFOS; perfluorosulfonamide (PFOSA; C8F17SO2NH2);
perfluorooctanoate (PFOA; C7F15CO2 ); and perfluorohexanesulfonate
(PFHS; C6F13SO3 ). Sera and liver samples were extracted using an ion-pairing
extraction procedure. The extracts were quantitatively assayed using HPLC-ESMSMS
and evaluated versus an unextracted curve. Extensive matrix spike studies were
performed to evaluate the precision and accuracy of the analysis. These matrix spike
studies indicated that the data can be considered to be accurate to within one standard
deviation of the average fortified sample recovery. For example, the average fortified
sample recovery of PFOS from human sera was 89% (SD 21%). The average fortified
sample recovery of PFOS from human liver was 78% (SD 24%).
A total of 31 donor samples (16 male, 15 female) were obtained over an 18 month
time period. Average age of the male donors was 50 years (SD 15.6, range 5-69) and 45
years (SD 18.5, range 13-74) for the female donors. Causes of death were intracranial
hemorrhage (n = 16, 52%), motor vehicle accident (n = 7, 23%), head trauma (n = 4,
13%), brain tumor (n = 2, 6%), drug overdose (N = 1, 3%) and respiratory arrest (n = 1,
3%).
Serum PFOS ranged from <6.1 (limit of quantitation, LOQ) to 58.3 ng/mL with a
mean of 17.7 ng/mL (95% Cl 13.0 - 22.5) for the average of the 24 donor samples
analyzed. In the calculation of arithmetic means, any serum PFOS values that were
determined to be <LOQ were assigned values midpoint between zero and the <LOQ.
Liver PFOS ranged from <3.7 (LOQ) to 57.0 ng/g with a mean of 18.8 ng/g (95% Cl 14.1
- 23.5) for the average of the 30 donor liver samples analyzed; likewise, any liver PFOS
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values that were determined to be <LOQ were assigned values midpoint between zero and the <LOQ. Fifteen (50%) of the 30 donors had liver analyses <LOQ.
A ranked distribution of the average PFOS serum and liver data for each of the 23 paired samples showed good correlation (Spearman's Rho = 0.41, p < .05). In these 23 pairs, the mean liver to serum ratio was 1.3:1 (95% Cl 0.9:1 - 1.7:1). Assuming the variation of the analytical error is one standard deviation, the mean liver:serum ratio ranged from a minimum of 0.8:1 (95% Cl 0.5 - 1.0) to a maximum of 2.1:1 (95% Cl 1.5 2.8). Although the study data were limited by the number of donors, it should be noted that the average serum PFOS levels determined in the present study were comparable to those reported elsewhere in nonoccupationally exposed human populations. The levels of PFOA, PFHS, and PFOSA were determined in the samples but we chose not to estimate liver:serum ratios for these analytes as 90% of the liver samples were determined to be <LOQ.
In conclusion, our data, as well as the data from the six month primate study, would suggest that a livenserum ratio that approximates 1:1 for the non-occupationallyexposed human population may be a reasonable assumption to use in a risk characterization assessment of PFOS. Assuming the variation of the analytical error is one standard deviation, the mean liver:serum ratio in our study would range from a minimum of 0.8:1 (95% Cl 0.5 - 1.0) to a maximum of 2.1:1 (95% Cl 1.5 - 2.8). We chose not to estimate mean livenserum ratios for PFOSA, PFOA and PFHS because 90% of these liver sample analyses were <LOQ.
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INTRODUCTION
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Evidence that organic fluorine can be characterized as a component of human
blood has existed for more than 30 years, although compound-specific characterization of
the organic fluorine was not complete (Guy et al, 1974). Hansen et al (2001) have
recently published an analytical method utilizing high performance liquid
chromatography/electrospray tandem mass spectrometry (HPLC/ESMSMS) to measure
specific perfluoroinated chemicals in human serum and animal serum and liver. Among
65 human serum samples purchased from biological supply companies, Hansen et al
reported perfluorooctanesulfonate (PFOS) may be the primary contributor to the total
organic fluorine levels in human sera. The average reported serum PFOS level was 28.4
ng/mL (SD 13.6, range 6.7-81.5 ng/mL). Lesser amounts of perfluorooctanoate (PFOA,
mean = 6.4 ng/mL, SD = 4.8), perfluorohexanesulfonate (PFHS, mean = 6.6 ng/mL, SD
= 5.1) and perfluorooctanesulfonamide (PFOSA, mean <1.6 ng/mL) were also
determined. Hansen et al calculated that the combined organic fluorine content of these
four fluorochemicals approximated the total organic fluorine measured by Guy et al in
the 1970's. Additional analyses of human serum from nonoccupationally exposed
population samples (3M Company, 1999) has collaborated the serum PFOS findings
reported by Hansen et al.
During their serum method development, Hansen et al (2001) also developed
comparable methods for the analysis of fluorochemical levels in animal liver. PFOS has
been demonstrated to primarily distribute into the liver (Johnson et al, 1979) and enter the
enterohepatic circulation. The scope of work described by Hansen et al did not include
the analysis of fluorochemicals in any human livers.
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In a recently completed six-month feeding study of PFOS to cynomolgus monkeys, liver to serum ratios at end of study were reported to be approximately 1:1 in the low- (0.03 mg/kg/day) and mid- (0.15 mg/kg/day) dose groups (Seacat et al, 2001). A linear increase in serum PFOS was observed throughout the course of study for the low- and mid-dose groups. In the primate study, PFOS was measured with comparable analytical techniques to those described by Hansen et al (2001). End-of-study low- and mid-dose groups' serum PFOS levels averaged 15 and 75 ppm, respectively, and liver PFOS levels averaged 20 and 60 ppm, respectively. No toxicologically significant effects were observed in the low- and mid-dose groups. A non-linear response with a plateau in serum levels was reported for the high dose group (0.75 mg/kg/day); decreased cholesterol was the most sensitive clinical response, occurring only at serum PFOS levels > 100 ppm. End-of-study serum and liver levels for the high-dose group averaged 172 ppm and 334 ppm, respectively. These studies suggested that serum PFOS levels may serve as an adequate marker of liver burden at levels less than 100 ppm .
The purpose of this investigation was to determine whether the 1:1 liver to serum ratio observed in the primate study in the low- and mid-dose groups also occurrs in individual, non-occupationally exposed humans. Previous measurements by Hansen et al (2001) and others (3M Company 1999), have indicated that the average serum PFOS levels in nonoccupationally exposed populations may be approximately three orders of magnitude lower than the average low-dose serum PFOS level (20 ppm) measured in the six month primate study by Seacat et al.
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METHODS
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Procurement of Human Tissue
All human sera and liver donor tissue were obtained through the International
Institute for the Advancement of Medicine (HAM). HAM is a non-profit organization
whose purpose is to facilitate the placement of non-transplantable human organs and
tissues for biomedical research and education (Bode 1997). HAM is a division of the
Pennsylvania Regional Tissue and Transplant Bank. This is an inspected and accredited
program which meets or exceeds all of the Food and Drug Administration (FDA) and
America Association of Tissue Banks (AATB) standards. HAM works with a network of
organ procurement organizations and tissue banks throughout the United States from
which tissues are received from postmortem donors. HAM abides by U.S. legislation
governing the consent process for organ and tissue donation in accordance with the
Uniform Anatomical Gift Act and Title III of the National Organ Transplant Act. HAM
ensures and guarantees donor confidentiality per Title 45, Part 46 of the U.S. Code of
Federal Regulations. All donors were tested for HIV-1 and HIV-2 antibodies, hepatitis B
surface antigen, hepatitis C antibody, HTLV-1 antibody, syphilis, and hepatitis B core
antibody (IgG plus IgM). In addition, one or more of the following tests were sometimes
done: CMV antibody, hepatitis B surface antibody, hepatitis B core IgM and HIV p24
antigen. Results that suggested the donor was infectious precluded the distribution of the
tissue. The Medical Department at the 3M Company completed an agreement with HAM
for human biological material for research use which included a letter of approval from
the 3M Institutional Review Board. Upon acceptable donor qualifications, HAM
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obtained 5 ml of blood and 10 grams of liver and then froze the samples until shipment to the 3M Medical Department.
Analysis of Samples All samples were analyzed for quantitative determination of four
perfluorochemicals: PFOS (CgFnSOs ), PFOSA (C8F17SO2NH2), PFOA (C7F15CO2 ) and PFHS (C6F13SO3 ). Sera and liver samples were extracted using an ion-pairing extraction procedure, as detailed by Hansen et al (2001). The extracts were quantitatively assayed using HPLC-ESMSMS and evaluated versus an unextracted curve. The difficulties presented by background levels of fluorochemical in samples of "blank" test matrix were circumvented by utilizing rabbit sera as a surrogate matrix for extraction blanks. The linear range was determined by analyzing duplicate curves over a wide range (approx. 0.005-1.00 ug/mL). Each sample was extracted and analyzed in duplicate.
Extensive matrix spike studies were performed to evaluate the precision and accuracy of the analysis. Thirty one matrix spikes were prepared in human sera and 41 spikes were prepared in human liver. Spikes were prepared to approximate the levels of PFOS determined in the samples. It is not possible to verify true recovery of endogenous analyte from tissues without radiolabeled reference material. The only measurement of accuracy available, matrix spike studies, indicated that the data can be considered to be accurate to within one standard deviation of the average fortified sample recovery. For PFOS, the average fortified sample recovery in human sera was 89% (SD 21%). The average fortified sample recovery of PFOS from human liver was 78% (SD 24%). For the remaining analytes, PFOSA, PFHS and PFOA the average fortified sample recovery
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in human sera were 86% (SD 30%), 55% (SD 26%) and 89% (SD 33%), respectively. Likewise, the average fortified sample recovery in human liver for these three analytes were 83% (SD 20%), 42% (SD 30%) and 67% (SD 30%), respectively. Results for sera are reported as ng/mL and for liver as ng/g.
RESULTS Serum and/or liver samples were obtained from 31 donors over an 18 month time
period (Table 1). Both serum and liver tissue were harvested from 23 donors; 7 donors contributed liver tissue only and 1 donor contributed serum only. Average age was 50 years (SD 15.6, range 5-69) for male donors (n = 16) and 45 years (SD 18.5, range 13-74) for female donors (n = 15). Causes of death as provided by HAM were intracranial hemorrhage (n = 16, 52%), motor vehicle accident (n = 7, 23%), head trauma (n = 4, 13%), brain tumor (n = 2, 6%), drug overdose (N = 1, 3%) and respiratory arrest (n = 1, 3%).
Serum and liver results for PFOS are provided in Table 2. Serum PFOS levels determined to be less than the limit of quantitation (<LOQ) were assigned a value midpoint between zero and the LOQ. Mean serum PFOS level was 17.7 ng/mL (95% Cl 13.0-22.5; range <6.1 - 58.3 ng/mL) for the average of the 24 serum donors' samples analyzed. The geometric mean for serum PFOS was 14.7 ng/mL (95% Cl 11.1 - 19.4). Similarly, PFOS liver samples that were determined to be <LOQ were assigned a value midpoint between zero and the LOQ. Fifteen (50%) of the 30 liver donors had liver PFOS results at <LOQ. The mean liver PFOS was 18.8 ng/g (95% Cl 14.1 - 23.5; range <3.7 - 57.0 ng/g) for the average of the 30 liver donors' samples analyzed. The geometric
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mean for liver PFOS was 15.2 ng/g (95% Cl 11.9 - 19.6). Mean PFOS levels between male and female donors for serum (male = 18.2 ng/mL; female = 17.2 ng/mL) or liver (male = 19.2 ng/g; female = 18.4 ng/g) were similar. No associations were observed between measured PFOS levels and age (data not shown).
A ranked distribution of the average PFOS serum and liver data for each of the 23 paired samples (sera and liver from the same individual) showed good correlation (Spearman's Rho = 0.41, p < .05). The mean liver to serum ratio was 1.3:1 (95% Cl 0.9 1.7; range 0.2 - 3.7) for these 23 pairs. There was no significant difference between genders. Of the 13 male donors with paired samples, the mean liver:serum ratio was 1.3:1 (95% Cl 0.8:1 - 1.9:1 ). Their mean serum and liver levels were 18.2 ng/mL (95% Cl 10.2 - 26.2) and 20.8 ng/g (95% Cl 11.4 - 30.1), respectively. Of the 10 female donors with paired samples, their mean liver:serum ratio was 1.3:1 (95% Cl 0.6:1 2.0:1). Their mean serum and liver levels were 16.9 ng/mL (95% Cl 10.0 - 23.7) and 16.3 ng/g (95% Cl 9.3 - 23.2), respectively.
In order to study the maximum livenserum ratio for PFOS, the average values were adjusted to accommodate the upper (liver) and lower (sera) quantitative limits described by the analytical accuracy (Table 3). As stated previously, the stated accuracy for PFOS determination in sera was 89+/-21% and 78+/-28% in liver. Assuming a one standard deviation increase in liver and one standard deviation decrease in serum, the livenserum ratio became 2.1:1 (95% Cl 1.5:1 - 2.8:1). In order to examine the lower limits of the livenserum ratio the average liver PFOS levels were decreased by one standard deviation deviation and the sera PFOS levels were increased by one standard deviation which resulted in a livenserum ratio of 0.8:1 (95% Cl 0.5:1 - 1.0:1). [Note:
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Assuming a two standard deviation increase in liver PFOS levels and a two standard deviation decrease in sera PFOS levels resulted in a maximum livenserum ratio of 3.4:1 (95% Cl 2.3:1 - 4.4:1). Likewise, a two standard deviation decrease in liver PFOS levels and a two standard deviation increase in sera PFOS levels resulted in a minimum livenserum ratio of 0.5:1 (95% Cl 0.3 - 0.6).
Provided in Tables 4 through 6 are the serum and liver values for the 31 donors for PFOSA, PFOA and PFHS, respectively. Unlike the results of PFOS determination where liver samples from 15 of the donors were determined to contain PFOS above the LOQ in at least one of the duplicate measurements, values greater than the LOQ for PFOSA, PFOA, and PFHS were sparse. A larger number of values less than the LOQ for PFOSA, PFOA, and PFHS were also determined in the analysis of sera samples. Serum values ranged from <LOQ (<1.3) to 22.1 ng/mL for PFOSA , < LOQ (<3.0) to 7.0 ng/mL for PFOA and < LOQ (<1.2) to 5.9 ng/mL for PFHS. Again, assuming the midpoint value between zero and the LOQ serum value for <LOQ samples, the mean serum PFOSA level was 4.5 ng/mL (95% Cl 2.6 - 6.5). The geometric mean for serum PFOSA was 3.0 ng/mL (95% Cl 2.0 - 4.4). The mean serum PFOA level was 3.1 ng/mL (95% Cl 1.9 4.3) with a geometric mean of 2.5 ng/mL (95% Cl 1.9 - 3.2). The mean serum PFHS level was 2.4 ng/mL (95% Cl 1.7 - 3.0) with a geometric mean of 1.8 ng/mL (95% Cl 1.3 - 2.6). We did not provide any liver/serum ratios in Tables 3 through 5 because more than 90% of the individual liver samples were determined to be <LOQ.
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DISCUSSION
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The purpose of this study was to estimate a mean liver:serum ratio in human
donors from a nonoccupationally exposed population. Our data indicated that at non
occupationally exposed population serum levels (approximately 30 ng/mL), the mean
livenserum ratio for PFOS was 1.3:1 (95% Cl 0.9 -1.7) which is similar to the 1:1 ratio
reported by Seacat et al (2001) in the low- and mid- dose groups in their six month
primate study. Serum PFOS levels measured at the end of this primate study were
considerably greater for the low- and mid-dose groups (average 20 and 75 ug/mL,
respectively) than what has been determined in sera samples from nonoccupationally
exposed human populations. Further refinement of this ratio for humans is unlikely
without more precise analytical techniques that can consistently measure PFOS at lower
levels as well as the other fluorochemical analytes that were measured this study.
Although the study data were limited by the number of donors (raising the question about
the representiveness of the sample set), it should be noted that the average serum PFOS
levels determined in the present study were comparable to those reported elsewhere
(Hansen et al, 2001; 3M Company, 1999).
In summary, our study data, as well as the results from the recently completed six
month primate study (Seacat et al, 2001), suggest that a livenserum ratio of 1:1 for the
nonoccupationally exposed human population may be a reasonable approximation to use
in a risk characterization process for PFOS. Assuming the variation of the analytical error
is one standard deviation, the mean livenserum ratio in our study would range from a
minimum of 0.8:1 (95% Cl 0.5 - 1.0) to a maximum of 2.1:1 (95% Cl 1.5 - 2.8). We
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chose not to estimate mean liver:serum ratios for PFOSA, PFOA and PFHS because 90%
of these liver sample analyses were <LOQ.
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REFERENCES
3M Company (1999). Perfluorooctane Sulfonate: Current Summary of Human Sera, Health and Toxicology Data. February 5, 1999 (unpublished report).
Bode DC (1997). Organization and activities of human tissue banks in the U.S. with special reference to the International Institute for the Advancement of Medicine. UNOS Bulletin. January/February 1997.
Guy WS, Taves DR, Brey WS. Organic fluorocompounds in human plasma: prevalence and characterization. Biochemistry Involving Carbon-Fluorine Bonds; ACS Symposium, 1976; pp 117-134.
Hansen KJ, Clemen LA, Ellefson ME, Johnson HO (2001). Compound-specific, quantitative characterization of organic fluorochemicals in biological matrices. Environ Sci Technol 35:766-770.
Johnson JD, Gibson SJ, Ober RE (1979). Extent and route of excretion and tissue distribution of total carbon-14 in rats after a single intravenous dose of FC-95-14C. St. PaukRiker Laboratories.
Seacat AM, Thomford PJ, Hansen KJ, Olsen GW, Case MT, Butenhoff JL (2001). Investigation of the no observeable effect level for perfluorooctanesulfonic acid potassium salt in cynomolgus monkeys after twenty-six weeks of oral dosing and one year of recovery. Toxicol Sciences (submitted).
Individual Ml M2 M3 M4 M5 M6 M7 M8 M9 MIO M il M12 M13 M14 M15
Table 1
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Demographic and Cause of Death Distribution of 31 Human Donors
Gender Male Male Male Male Male Male Male Male Male Male Male Male Male Male Male
Race White White Hispanic Black White Hispanic White White White White Hispanic White Asian White White
Tissue Available
Age
Cause of Death
Serum
Liver
5
MVA
No
Yes
34
Brain tumor
Yes
Yes
38
MVA
Yes
Yes
41
Head trauma
Yes
Yes
43
MVA**
Yes
Yes
46 ICH Yes Yes
52
Head trauma
Yes
Yes
55 ICH Yes Yes
56
MVA
Yes
Yes
56
Head trauma
Yes
Yes
57 ICH Yes Yes
58 ICH No Yes
60 ICH No Yes
64
ICH*
Yes
Yes
64 ICH Yes Yes
M16
Male
White
Table 1 (continued) 69
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Yes
FI
Female
White
13
Brain tumor
No
Yes
F2
Female
White
18
MVA
No
Yes
F3
Female
White
26
Drug overdose
Yes
Yes
F4
Female
White
30
Respiratory arrest
Yes
Yes
F5
Female
White
37
ICH Yes Yes
F6
Female
White
38
MVA
No
Yes
F7
Female
White
42
ICH Yes
No
F8
Female
Unknown
44
ICH Yes Yes
F9
Female
White
47
ICH Yes Yes
FIO
Female
White
51
MVA
Yes
Yes
F ll
Female
White
58
ICH Yes Yes
F12
Female
White
60
ICH Yes Yes
F13
Female
White
66
ICH Yes Yes
F14
Female
White
70
Head trauma
Yes
Yes
F15
Female
White
74
ICH No
Yes
*ICH = Intracranial hemorrhage **MVA = Motor vehicle accident
Table 2
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PFOS Serum, Liver and Liver Serum Ratios for 31 Human Donors
_____________ Serum (ng/ml)_____________ ______________ Liver (ng/g)______________ Individual___________ Analysis_____________ Mean_______________ Analysis_____________ Mean_________ Liver/Serum Ratio
Ml No serum
<LOQ (18.4) <LOQ (18.4)
<LOQ (18.4)
M2
13.9
13.6
<LOQ (4.5)
<4.5
<0.3:1
13.2 4.5
M3
9.8
10.3
<LOQ (18.4)
<LOQ (18.4)
<1.8:1
10.8 <LOQ (18.4)
M4 15.6 16.0 16.4
13.4 15.7 18.0
1.0:1
M5 15.5 16.0 16.5
36.4 40.0 43.6
2.5:1
M6
20.4
19.5
<LOQ (18.4)
<LOQ (18.4)
<1.0:1
18.6 <LOQ (18.4)
M7
9.4
9.5
<LOQ (36.8)
<LOQ (36.8
<3.9:1
9.5 <LOQ (36.8)
M8 7.4 7.6 7.7
22.7 21.7 20.7
2.9:1
M9 25.3 24.9 24.5
14.6 15.4 0.6:1 16.2
MIO 14.5 14.2 13.9
12.4 11.4 0.8:1 10.4
M il M12 M13 M14 M15 M16 FI F2 F3 F4 F5 F6
11.9 13.9 No serum
No serum
58.3 55.7 29.4 25.9 8.1 6.9 No serum
No serum
14.2 14.3 31.2 28.5 19.3 20.1 No serum
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Table 2 (continued)
12.9
<LOQ (18.4)
<LOQ (18.4)
<LOQ (18.4)
- 18.9 18.7 18.5
-
<LOQ (18.4)
<LOQ (18.4)
<LOQ (18.4)
57.0 47.0 44.2 41.4
27.6 57.0 53.8 50.6
7.5
<LOQ (36.8)
<LOQ (36.8)
<LOQ (36.8)
-
<LOQ (36.8)
<LOQ (36.8)
<LOQ (36.8)
- 17.2 17.1 16.9
14.2
<LOQ (32.6)
<LOQ (32.6)
<LOQ (32.6)
29.8
<LOQ (32.6)
<LOQ (32.6)
<LOQ (32.6)
19.7
<LOQ (7.3)
<LOQ (7.3)
<LOQ (7.3)
- 23.6 <LOQ (18.4)
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<1.4:1
-
-
<0.8:1 1.9:1
<4.9:1
-
-
<2.3:1 <1.1:1 <0.4:1
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Table 2 (continued)
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F7 20.5 20.6 No liver 20.7
F8 22.9 24.7 26.5
26.5 23.7 <1.0:1 20.9
F9
3.0
2.7
<LOQ (18.4)
<LOQ (18.4)
<6.8:1
2.4 <LOQ (7.3)
FIO
<LOQ (6.1)
<6.9
6.9
<LOQ (36.8) <LOQ (36.8)
<LOQ (36.8)
<5.3:1
F ll 26.0 21.3 16.6
25.2 27.0 28.9
1.3:1
F12
8.2
7.4
<LOQ (18.4)
<LOQ (18.4)
<2.5:1
6.5 <LOQ (18.4)
F13
15.8
15.6
<LOQ (16.3)
<LOQ (16.3)
<1.1:1
15.3 <LOQ (16.3)
F14 24.5 28.4 32.2
39.3 33.5 <1.2:1 27.8
F15 No serum
42.2 42.5 42.7
Limit Described Average Lower Limit I Upper Limit I Lower Limit II Upper Limit II
Table 3
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Liver [PFOS]:Serum [PFOS] Ratio Analysis
Alterations
Liver [PFOS]:Serum [PFOS] Ratio
95% C.I. of Ratio
None
1.3:1 0.9:1- 1.7:1
Liver PFOS decreased 1 SD* Serum PFOS increased 1 SD**
0.8:1
0.5:1 - 1.0:1
Liver PFOS increased 1 SD Serum PFOS decreased 1 SD
2.1:1
1.5:1 -2.8:1
Liver PFOS decreased 2 SD Serum PFOS increased 2 SD
0.5:1
0.3:1 -0.6:1
Liver PFOS increased 2 SD Serum PFOS decreased 2 SD
3.4:1
2.3:1 -4.4:1
*Liver [PFOS] SD = 24% **Serum [PFOS] SD = 21%
Individual Ml M2 M3 M4 M5 M6 M7 M8 M9 MIO
Table 4
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PFOSA Serum and Liver Analyses for 31 Human Donors
_____ Serum (ng/ml)_____ Analysis___________Mean
_______Liver (nfi/g) Analysis__________ Mean
No serum
<LOQ (18.8) <LOQ (18.8)
<LOQ (18.8)
<LOQ (1.3) <LOQ (1.3)
<LOQ (1.3)
<LOQ (7.5) <LOQ (7.5)
<LOQ (7.5)
2.0
2.7
<LOQ (18.8)
<LOQ (18.8)
3.4 <LOQ (18.8)
9.9
9.6
<LOQ (7.6)
<LOQ (7.6)
9.3 <LOQ (7.6)
<LOQ (1.3) <LOQ (1.3)
<LOQ (1.3)
<LOQ (7.5) <LOQ (7.5)
<LOQ (7.5)
6.4
6.1
<LOQ (18.8)
<LOQ (18.8)
5.9 <LOQ (18.8)
<LOQ (3.1) <LOQ (3.1)
<LOQ (3.1)
<LOQ (18.8) <LOQ (18.8)
<LOQ (18.8)
4.4
6.8
<LOQ (18.8)
<LOQ (18.8)
9.2 <LOQ (18.8)
<LOQ (3.3) <LOQ (3.3)
<LOQ (3.3)
<LOQ (7.9) <LOQ (7.9)
<LOQ (7.9)
12.8
12.9
<LOQ (7.5)
<LOQ (17.5)
13.0 <LOQ (7.5)
Table 4 (continued)
M il 5.1 5.1 5.1
M12
No serum
--
M13 No serum -
M14 3.6 3.7 3.8
M15 2.9 3.2 3.5
M16
<LOQ (3.1)
<LOQ (3
<LOQ (3.1)
FI
No serum
-
F2
No serum
-
F3
<LOQ (1.3)
<1.3
1.3
F4 2.2 2.1 2.0
F5
<LOQ (1.3)
<LOQ (1
<LOQ (1.3)
F6
No serum
_
BACK TO MAIN
<LOQ (18.8) <LOQ (18.8)
<LOQ (18.8)
3M Company EPI-0018
Page 22 of 29
<LOQ (19.6) <LOQ (19.6)
<LOQ (19.6)
<LOQ (18.8) <LOQ (18.8)
<LOQ (18.8)
<LOQ (7.5) <LOQ (7.5)
<LOQ (7.5)
<LOQ (19.6) <LOQ (19.6)
<LOQ (19.6)
<LOQ (18.8) <LOQ (18.8)
<LOQ (18.8)
<LOQ (18.8) <LOQ (18.8)
<LOQ (18.8)
<LOQ (19.6) <LOQ (19.6)
<LOQ (19.6)
<LOQ (7.9) <LOQ (7.9)
<LOQ (7.9)
<LOQ (7.9) <LOQ (7.9)
<LOQ (7.9)
<LOQ (7.5) <LOQ (7.5)
<LOQ (7.5)
<LOQ (18.8) <LOQ (18.8)
<LOQ (18.8)
Table 4 (continued)
F7 2.5 2.8 3.1
F8 7.9 10.0 12.1
F9 1.6 1.5 1.5
F10
<LOQ (3.1)
<LOQ (3.1)
<LOQ (3.1)
F ll 7.5 6.5 5.5
F12 5.0 4.5 4.0
F13
<LOQ (3.3)
<LOQ (3.3)
<LOQ (3.3)
F14 17.8 20.0 22.1
F15 No serum
BACK TO MAIN
No liver
-
3M Company EPI-0018
Page 23 of 29
<LOQ (18.8) <LOQ (18.8)
6.3 <LOQ (7.5)
<LOQ (18.8) <LOQ (18.8)
<LOQ (19.6) <LOQ (19.6)
<LOQ (18.8) <LOQ (18.8)
<LOQ (7.9) <LOQ (7.9)
<LOQ (18.8) <LOQ (18.8)
<LOQ (19.6) <LOQ (19.6)
<LOQ (18.8) <LOQ (7.5) <LOQ (18.8) <LOQ (19.6) <LOQ (18.8) <LOQ (7.9) <LOQ (18.8) <LOQ (19.6)
Table 5
BACK TO MAIN
3M Company EPI-0018
Page 24 of 29
PFOA Serum and Liver Analyses for 31 Human Donors
__________ Serum (ng/ml)__________ ___________ Liver (ng/g)______ Individual___________ Analysis__________ Mean_____________Analysis__________ Mean
Ml No serum
<LOQ (17.9) <LOQ (17.9)
<LOQ (17.9)
M2
2.1
2.1
<LOQ (5.4)
<LOQ (5.4)
2.0 2.5
M3
<LOQ (3.0)
<LOQ (3.0)
<LOQ (17.9)
<LOQ (17.9)
<LOQ (3.0)
<LOQ (17.9)
M4
15.6 14.7
50.0 46.9
13.8 43.8
M5
<LOQ (6.0)
<LOQ (6.0)
<LOQ (35.9)
<LOQ (35.9)
<LOQ (6.0)
<LOQ (35.9)
M6
6.7
6.1
<LOQ (17.9)
<LOQ (17.9)
5.5 <LOQ (17.9)
M7
<LOQ (3.0)
<LOQ (3.0)
<LOQ (17.9)
<LOQ (17.9)
<LOQ (3.0)
<LOQ (17.9)
M8
<LOQ (3.0)
<LOQ (3.0)
<LOQ (17.9)
<LOQ (17.9)
<LOQ (3.0)
<LOQ (17.9)
M9
3.3
3.2
<LOQ (18.7)
<LOQ (18.7)
3.1 <LOQ (18.7)
MIO
<LOQ (3.0)
<LOQ (3.0)
<LOQ (17.9)
<LOQ (17.9)
<LOQ (3.0)
<LOQ (17.9)
Table 5 (continued)
M il
<LOQ (3.0)
<LOQ (3.0)
<LOQ (3.0)
M12
No serum
-
M13 No serum -
M14 7.0 <7.0 <LOQ (6.0)
M15 5.6 5.3 4.9
M16
<LOQ (3.0)
<LOQ (3.0)
<LOQ (3.0)
FI
No serum
-
F2
No serum
-
F3
<LOQ (3.1)
<LOQ (3.1)
<LOQ (3.1)
F4
<LOQ (3.1)
<LOQ (3.1)
<LOQ (3.1)
F5 3.0 <3.0 <LOQ (3.0)
F6
No serum
.
BACK TO MAIN
<LOQ (17.9) <LOQ (17.9)
<LOQ (17.9)
3M Company EPI-0018
Page 25 of 29
<LOQ (18.7) <LOQ (18.7)
<LOQ (18.7)
<LOQ (17.9) <LOQ (17.9)
<LOQ (17.9)
<LOQ (35.9) <LOQ (35.9)
<LOQ (35.9)
<LOQ (18.7) <LOQ (18.7)
<LOQ (18.7)
<LOQ (17.9) <LOQ (17.9)
<LOQ (17.9)
<LOQ (17.9) <LOQ (17.9)
<LOQ (17.9)
<LOQ (18.7) <LOQ (18.7)
<LOQ (18.7)
<LOQ (18.7) <LOQ (18.7)
<LOQ (18.7)
<LOQ (18.7) <LOQ (18.7)
<LOQ (18.7)
<LOQ (17.9) <LOQ (17.9)
<LOQ (17.9)
<LOQ (17.9) <LOQ (17.9)
<LOQ (17.9)
Table 5 (continued)
F7 3.4 <3.4 <LOQ (3.0)
F8
<LOQ (3.0)
<LOQ (3.0)
<LOQ (3.0)
F9
<LOQ (3.0)
<LOQ (3.0)
<LOQ (3.0)
F10
<LOQ (3.0)
<LOQ (3.0)
<LOQ (3.0)
F ll 3.8 3.1 2.5
F12
<LOQ (3.0)
<LOQ (3.0)
<LOQ (3.0)
F13 3.5 3.7 4.0
F14 5.1 5.5 5.9
F15 No serum
BACK TO MAIN
No liver
"
3M Company EPI-0018
Page 26 of 29
<LOQ (17.9) <LOQ (17.9)
<LOQ (35.9) <LOQ (17.9)
<LOQ (17.9) <LOQ (17.9)
<LOQ (18.7) <LOQ (18.7)
<LOQ (17.9) <LOQ (17.9)
<LOQ (18.7) <LOQ (18.7)
<LOQ (17.9) <LOQ (17.9)
<LOQ (18.7) <LOQ (18.7)
<LOQ (17.9) <LOQ (35.9) <LOQ (17.9) <LOQ (18.7) <LOQ (17.9) <LOQ (18.7) <LOQ (17.9) <LOQ (18.7)
Individual Ml M2 M3 M4 M5 M6 M7 M8 M9 MIO
Table 6
BACK TO MAIN
3M Company EPI-0018
Page 27 of 29
PFHS Serum and Liver Analyses for 31 Human Donors
_____ Serum (ng/ml)_____ Analysis__________ Mean
_______Liver (ng/g) Analysis__________ Mean
No serum
<LOQ (3.7) <LOQ (3.7)
<LOQ (3.7)
4.1
4.1
<LOQ (3.4)
<LOQ (3.4)
4.0 1.4
2.5
2.8
<LOQ (3.7)
<LOQ (3.7)
3.0 <LOQ (3.7)
<LOQ (5.7) <LOQ (5.7)
<LOQ (5.7)
Not analyzed
-
3.1
2.9
<LOQ (3.4)
<LOQ (3.4)
2.6 <LOQ (3.4)
0.8
0.7
<LOQ (3.7)
<LOQ (3.7)
0.6 <LOQ (3.7)
4.9
4.8
<LOQ (18.5)
<LOQ (18.5)
4.8 <LOQ (18.5)
0.4
0.4
<LOQ (3.7)
<LOQ (3.7)
0.4 <LOQ (3.7)
3.2
3.3
<LOQ (3.7)
<LOQ (3.7)
3.4 <LOQ (3.7)
<LOQ (1.2) <LOQ (1.2)
<LOQ (1.2)
<LOQ (7.4) <LOQ (7.4)
<LOQ (7.4)
Table 6 (continued)
M il 3.7 3.7 3.6
M12
No serum
-
M13
No serum
-
M14 3.7 3.5 3.3
M15 5.9 5.6 5.3
M16
<LOQ (3.1)
<LOQ (3
<LOQ (3.1)
FI
No serum
-
F2
No serum
-
F3 1.4 1.5 1.5
F4 2.0 1.9 1.8
F5
<LOQ (1.2)
<LOQ (1
<LOQ (1.2)
F6
No serum
_
BACK TO MAIN
<LOQ (3.7) <LOQ (3.7)
<LOQ (3.7)
3M Company EPI-0018
Page 28 of 29
<LOQ (3.7) <LOQ (3.7)
<LOQ (3.7)
<LOQ (3.7) <LOQ (3.7)
<LOQ (3.7)
<LOQ (3.4) <LOQ (3.4)
<LOQ (3.4)
7.5 8.2 8.9
<LOQ (18.5) <LOQ (18.5)
<LOQ (18.5)
<LOQ (18.5) <LOQ (18.5)
<LOQ (18.5)
<LOQ (3.7) <LOQ (3.7)
<LOQ (3.7)
<LOQ (7.4) <LOQ (7.4)
<LOQ (7.4)
<LOQ (7.4) <LOQ (7.4)
<LOQ (7.4)
<LOQ (7.4) <LOQ (7.4)
<LOQ (7.4)
<LOQ (3.7) <LOQ (3.7)
<LOQ (3.7)
Table 6 (continued)
F7 1.1 1.2 1.3
F8 3.0 3.1 3.2
F9
<LOQ (1.2)
<LOQ (1.2)
<LOQ (1.2)
F10 4.7 4.7 4.7
F ll 2.0 1.6 1.3
F12 0.5 0.5 0.4
F13 2.1 2.3 2.4
F14 2.3 2.7 3.0
F15 No serum
BACK TO MAIN
No liver
"
3M Company EPI-0018
Page 29 of 29
<LOQ (3.7) <LOQ (3.7)
5.6 <LOQ (7.4)
<LOQ (18.5) <LOQ (18.5)
<LOQ (3.7) <LOQ (3.7)
<LOQ (3.7) <LOQ (3.7)
<LOQ (3.7) <LOQ (3.7)
<LOQ (3.7) <LOQ (3.7)
<LOQ (3.4) <LOQ (3.4)
<LOQ (3.7) <LOQ (7.4) <LOQ (18.5) <LOQ (3.7) <LOQ (3.7) <LOQ (3.7) <LOQ (3.7) <LOQ (3.4)
