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JOEM • Volume 48, Number 8, August 2006
759
Community Exposure
Relationships Between
and Exposure Sources
Edward Anthony Emmett, MD, MS
Frances Susan Shofer, PhD
Hong Zhang, MD, MPH
David Freeman, MS
Chintan Desai, BSc
Leslie Michael Shaw, PhD
to Perfluorooctanoate:
Serum Concentrations
luoropolymers are used in a variety
of industrial and consumer products,
including non-stick cookware, water-
proof, breathable textiles, consumer
house wares, electronics, aerospace,
and other applications. Perfluoro-
octanoate (PFOA, CF3, [CF,16 C00—,
CAS No. 3825-26-1) also occurs as a
contaminant in other fluorochemi-
Objeetive: The objective of this study was to determine serum call and telomer products. Telomers
(perfluorooctanoate [PFOA]) in residents near a fluoropolymer produc- are highly fluorinated compounds used
tion facility: the contributions from air, water, and occupational in protective coatings for carpets,
exposures, personal and dietary habits, and relationships to age and paper, construction materials, and
gender. Methods: The authors conducted questionnaire and .serum
PFOA measurements in a stratified random sample and volunteers
residing in locations with the same residential water supply but with
higher and lower potential air PFOA exposure. Results: Serum (PFOA)
greatly exceeded general population medians. Occupational exposure
from production processes using PFOA and residential water had
additive effects; no other occupations contributed. Serum (PTOA)
depended on the source of residential drinking water, and not potential
air exposure. Tor public water users, the best fit model included age, tap
water drinks per day, servings of home grown fruit and vegetables, and
carbon filter use. Conclusions: Residential water source was the primary
determinant of serum (PTOA). U Occup Environ Med. 2006;48:
759-770)
From the University of Pennsylvania (Dr Emmett, Dr Shofer, Mr Desai, Dr Shaw), School of
Medicine, Philadelphia, Pennsylvania; Grand Central Family Medicine (Dr Zhang), Parkersburg, West
Virginia; and the Decatur Community Association (Mr Freeman), Cuter, Ohio.
This study was supported by grant ES12591 from the Environmental Justice Program of the U.S.
National Institute for Environmental Health Sciences (NIEHS), National Institutes of Health, and by
P30 Core Center grant ES 013508 from the NIEHS.
Address correspondence to: Edward A. Emmett, MD, Occupational Medicine, Silverstein Pavilion,
Ground Floor, 3400 Spruce St., Philadelphia, PA 19104-4284; E-mail: [e-mail].
Copyright 0 2006 by American College of Occupational and Environmental Medicine
DOI: 10.1097/01.jom.0000232486.07658.74
apparel, and in insecticide formula-
tions and high performance surfac-
tant products.
PFOA has commercial use primar-
ily as ammonium perfluorooctanoate,
an essential surface-active agent in the
production of various fluoropolymers,
including tetrafluoroethylene. PFOA is
a contaminant in other fluorochemicals
and telomer products.' According to
manufacturers, it is typically not
present in finished consumer articles.
Ammonium perfluorooctanoate is
fully dissociated into the anion form,
perfluorooctanoate, in environmental
media and biologic fluids.
Organofluorine compounds behave
very differently to the more widely stud-
ied organochlorines and organobromines
and have unusual partitioning proper-
ties.Z Perfluorofatty and perfluorosulfo-
nic acids, particularly PFOA and
perfluorooctane sulfonate (PFOS), are
now found ubiquitously in marine ani-
mals inhabiting widely spread geo-
graphic biospheres3 and in human serum
from widely disparate groups. 4-7 PFOA
and PFOS persist in the environment and
resist biologic, environmental, and pho-
F
DEQ-CFW 00000919

760
tochemical degradation (3M, 2001).
They have no known natural sources."
In the general U.S. population, me-
dian serum PFOA values are around 4
to 5 ng/mL; occasional values are
above 20 ng/mO,5,9 with no signifi-
cant gender differences. Analyses of
blood samples from residents near
Washington County, Maryland, found
a twofold increase in serum PFOA
levels between 1974 and 1989.6
Kannan et al' have reported differ-
ences in blood serum PFOA levels
among populations from different
countries.
PFOA toxicology has recently
been reviewed.' PFOA is well ab-
sorbed by rats after both oral and
inhalation exposure. Fecal excretion
in male rats is increased by feeding
cholestyramine resin, suggesting en-
terohepatic circulation.10 Dermal
penetration is significant in rats but
is low to negligible in humans. r r In
rats, PFOA is a peroxisome prolif-
erator activated receptor (PPAR) ag-
onist causing liver toxicityL2,13 with
hepatomegaly and hepatic necrosis,
and biochemical effects characteris-
tic of PPAR agonists." PFOA pro-
motes liver carcinogenesis in rats,'-5
and causes Leydig-cell testicular tu-
mors and acinar cell pancreatic tu-
mors16,17 through nongenotoxic
mechanismsrs.ry with questionable
human relevance. The human half-
life of PFOA was between 4 and 5
years for retirees with previous heavy
occupational exposure,20 much longer
than in laboratory animals.
Control of human exposure to
PFOA has been limited by the lack
of information on sources and path-
ways. As the U.S. Environmental
Protection Agency (EPA) states, "At
present, there aren't any steps that
EPA recommends that consumers
take to reduce exposure to PFOA
because the sources of PFOA in the
environment and the pathways by
which people are exposed are un-
known. The limited geographic loca-
tions of fluorochemical plants
making or using the chemical sug-
gest that there may be additional
sources of PFOA in the environment
Community Exposure to Perfluorooctanoate • Emmett et al
and exposures beyond those attribut-
able to direct releases from industrial
facilities. But whether human expo-
sures are due to PFOA in the air, the
water, on dusts or sediments in dietary
sources or through some combination
of routes is currently unknown.',21
PFOA has been used in the manu-
facturing of fluoropolymers at a facil-
ity in Washington, West Virginia,
since 1951. Potential airborne PFOA
exposure was modeled using informa-
tion on releases from the plant, mete-
orologic conditions, and topography.
The wind rose map, which shows the
frequency and strength of winds from
different directions, for the plant indi-
cates the primary wind direction, to-
ward the north/northeast, would carry
airborne emissions into neighboring
Ohio. PFOA was also released to the
Ohio River, adjacent to the plant, as
well as disposed in landfills and sur-
face impoundments in the vicinity. Ac-
cording to the facility, total PFOA
emissions from the facility have been
reduced from 87,000 lbs (31,000 air,
.56,000 water) and 80,000 lbs (31,000
air, 49,000 water) in 1999 and 2000,
respectively, to 11,000 lbs (6000 air,
5000 water) and 1700 lbs (200 air,
1500 water) in 2003 and 2004,
respectively.
PFOA has been detected in public
and private drinking water supplies
near the facility. The highest levels
reported in public water supplies in the
United States to date have been in the
Little Hocking water system, in oper-
ation since 1968, which draws water
from wells across the Ohio river from
the facility. The average PFOA in
Little Hocking system distribution wa-
ter for 2002-2005 has been 3.55
ng/mL (range, 1.5-7.2 ng/mL).
The objectives of the present study
were to measure serum PFOA levels in
a stratified random sample of the pop-
ulation served by the Little Hocking
water service to determine: how the
serum PFOA levels compared with
levels measured in other populations;
the relative contributions of air and
water exposure to serum PFOA levels;
and to determine the effects, if any, of
demographic variables, occupational
exposures, personal habits, use of
water filters, and dietary factors such
as the ingestion of locally harvested
game and fish and of homegrown
vegetables.
Materials and Methods
Eligibility Criteria
Eligibility criteria for participation
in the study were:
Residence in the area serviced by
the Little Hocking Water Associa-
tion for at least the past 2 years as
of July 2004;
Ages 2 or older (changed to ages 4
or older after the study began to
minimize participant discomfort);
and
Not known to have a bleeding
disorder (to diminish any risk from
phlebotomy).
Selection of Households for
Sampling Frame
Two populations of residents were
identified for participation in the strat-
ified random sampling. One popula-
tion represented those whose residence
was potentially exposed to PFOA in
both air and water, and the other whose
residence was potentially exposed to
PFOA in water but had very minimal
potential for exposure in air. The sam-
pling randomly selected households
from each of these strata.
To identify areas where there was
higher exposure to PFOA in the air,
we used an air dispersion model that
estimated the air concentration for
PFOA emanating from the PFOA
source plant. Inputs into the air dis-
persion model included the amounts
of air emissions for the plant, wind
velocities, and topographic contours.
The air concentrations had been
modeled for years 2002 and 2003 on
an annual basis; the model produced
very similar results for each of these
years. To identify areas in the Little
Hocking water service distribution
area, a map of the water distribution
system was obtained for the Little
Hocking water service. The potential
air and water exposure group com-
prised all those who had resided for
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JOEM • Volume 48, Number 8, August 2006
6.5 Tmles _­­l
® h' u&Yival Aire & Wader Expanure
V3ir Mglwx A & Wader Exposure
■ Saurce Fauibdy (SF)
13 Ot" Diver
Fig. 1. Map showing the locations of the studied communities and the source facility. Subjects
for the minimal air exposure group were selected from the area shown in yellow; subjects for the
higher air exposure group from the area are shown in red. Residents in both of these areas
obtained their water- from the same public residential water supply. The location of the source
facility is shown in black. The residents lived in Ohio; the source facility is located in West
Virginia. The state boundary, the Ohio River, is shown in blue.
at least 2 years in the water distribu-
tion system area of the Little Hock-
ing water service and also within the
contour line representing 0.2 µg/m3
PFOA in the air as a yearly average
for 2002. These households were all
located in portions of zip codes
45714 (Belpre) and 45742 (Little
Hocking).
The potential water exposure
group comprised residents who had
resided for at least 2 years in the
water distribution system area of the
Little Hocking water service but in
an area where air exposure to PFOA
from the facility was negligible. The
selected study area was zip codes
45724 (Cutler) and 45784 (Vincent).
These areas were all at least several
miles outside the lowest air concen-
tration contours derived from the air
dispersion model. Figure 1 shows the
location of the residence areas for
both the potential air and water ex-
posure and the potential water -only
exposure zones.
To identify households and resi-
dents in the zip codes of interest, de-
mographic and other information were
purchased from www.infousa, a pro-
prietary database of detailed informa-
tion on U.S. consumer households
compiled from thousands of public
sources. The items used to select invi-
tees were names of head of household,
street address, city, state, zip code, and
length of residence.
Selection of Stratified Random
Sample. For the area identified as hav-
ing both air and water exposure, 95
households in the www.infousa data-
base met the requirements; all were
invited to take part in the study. These
included households with measured
PFOA levels in potable well water
measured by the Ohio Department of
Environmental Protection and house-
holds using Little Hocking Water As-
761
sociation water. For the area identified
as having only water exposure to
PFOA, a stratified random sampling of
households was performed, resulting
in the selection of 342 households. All
members of selected households who
met the study eligibility criteria were
invited to participate.
Invitations to Participate. Invita-
tion letters were sent from the
University of Pennsylvania to each
selected household. If no response was
received, a second mailing was sent. If
there was still no response after ap-
proximately 10 days, a telephone call
was made to the household by staff of
the Decatur Community Association.
No participant chose an option for
anonymous participation. On the
weekend before the mailing of the
invitation letter, a flyer was placed in
the area weekend newspaper to an-
nounce that invitation letters were
forthcoming. The principal local news-
paper, the Marietta Times, indepen-
dently wrote an editorial encouraging
those selected to consider participation.
Community Volunteer Group. Be-
cause of great community interest, a
lottery was conducted to select an
additional sample of invitees from
households that volunteered to par-
ticipate in the study in response to a
newsletter notice. Those households
that met study criteria, including re-
siding in one of the areas used for
stratified random sampling, were in-
cluded in the lottery.
Administration of Questionnaires
Administration of questionnaires
and collection of blood samples were
performed between July 2004 and
February 2005 in nearby Parkers-
burg, West Virginia. The question-
naires were developed and revised
after review by the members of the
Community Advisory Committee and
an expert panel from the U.S. EPA.
The Community Advisory Committee,
convened by the Decatur Community
Association, comprised representatives
of the townships in the Little Hocking
Water Association Service District,
representatives from the Ohio and U.S.
EPA, the Warren School District, and
DEQ-CFW 00000921

762
the County Health Commissioner. Be-
fore finalization, the questionnaires
were pilot tested on a representative
group of 20 individuals from similar
southeastern Ohio or western West
Virginia communities, who did not
live in the Little Hocking Water Asso-
ciation District.
Trained interviewers administered
all questionnaires. Only one person
from each household supplied house-
hold information. The household ques-
tionnaire elicited information to ensure
that participants met the eligibility cri-
teria, demographic information on eli-
gible participants, household contact
information, sources of residential
drinking water (private well, water dis-
trict, cisterns, bottled water, hauled
water, and so on), use of a home water
filter, and water source and estimated
use for cooking, canning, and reconsti-
tuting canned soups and frozen juices.
All adults 18 years and older were
administered the adult questionnaire
that elicited demographic informa-
tion, diet (including consumption of
vegetables or fruit grown in your
garden, meat or game grown locally,
and fish caught locally), health con-
ditions (lives, thyroid, bleeding dis-
orders), current medications, current
occupational or school if a full-time
student, employment (including at a
facility using PFOA, visiting or pro-
cessing waste from that facility,
work as a firefighter, in carpet clean-
ing or retreating carpets or rugs, or in
professional carpet installation), and
smoking and alcohol habits.
All children were administered a
questionnaire that was similar to the
adult questionnaire except that the ques-
tions about occupation and about smok-
ing and alcohol habits were omitted.
Collection and Assay of PFOA
Acid in Serum
Specimen Collection. Twenty mil-
liliters of blood were drawn into red -
topped Vacutainer tube for PFOA
analysis, immediately centrifuged, and
the resulting serum was transferred to
polypropylene aliquot tubes, labeled,
and shipped on dry ice to the analysis
Community Exposure to Perfluorooctanoate • Emmett et al
laboratory (Exygen Research) where it
was stored at —80°C pending analysis.
Standards and Chemicals. The
standard for perfluorooctanoic acid
(99.2%) was obtained from Oakwood
Products, Inc. (West Columbia, SC)
and characterized by DuPont (Newark,
DE). Analysis by 19F NMR confirmed
that the PFOA standard contained
98.7% straight chain PFOA and
0.53% branched PFOA isomers. The
internal standard, [1,2-13C]-PFOA
(C6F13CF,"CO2H, 13C-PFOA)
(96.4%) was provided by DuPont.
Chemicals and reagents used in the
sample preparation procedure or in the
mobile phase were of reagent grade
and were obtained from VWR Scien-
tific (Bridgeport, NJ) and Sigma -
Aldrich (St. Louis, MO). Solvents
used for the mobile phase (acetonitrile,
water) were of HPLC grade and were
obtained from EM Science (Gibbs-
town, NJ). The control human senim
was purchased from Lampire Biologi-
cal Laboratories, Inc. (Pipersville, PA)
and stored frozen at —20°C. This fluid
was used for the preparation of labo-
ratory quality control samples with
spiked -in PFOA.
Chromatographic and Mass Spec-
trometric Conditions. PFOA was an-
alyzed through HPLC/tandem mass
spectrometry by a slight modifica-
tion of the method of Flaherty et al.22
Standards, Sample Preparation,
and Calibration. Controls and study
subject samples were added to 300
µL of acetonitrile. The samples were
thoroughly mixed by vortexing, centri-
fuged, and 5 µL of the cell- and protein -
free supernatant used for analysis by the
HPLC tandem mass spectrometer sys-
tem. A seven -point calibration curve was
analyzed throughout the analytical se-
quence for the fluorocompounds.
The calibrators included normal hu-
man serum spiked with 0.5, 1, 5, 10,
20, 50, and 100 ng/mL of PFOA. The
instrument response versus the cali-
brator concentration was plotted for
each point. Linear regression with
1/X weighting was used to deter-
mine the slope, y-intercept, and
coefficient of determination (t). Cali-
bration curves were deemed acceptable
if tz �0.985. This is the external
standardization method used for the
determination of PFOA in the set of
408 samples described in this study.
For samples with PFOA concentra-
tions > 100 ng/mL, the sample was
diluted in 50:50 methanol/water and
rerun. In addition, the analysis of
PFOA was done using 13C-perfluo-
rooctanoic acid as an internal stan-
dard for a randomly selected set of
35 of the samples to certify that the
external standardization method used
provided equivalent PFOA concen-
tration values. For these analyses, the
internal standard was mixed in ace-
tonitrile at a concentration of 1 ng/
mL. As described previously for the
externally standardized assay for
sample preparation: to 100 µL of
standards, controls and study subject
samples was added to 300 mL of
acetonitrile containing the internal
standard and the cell- and protein -
free supernatants prepared as de-
scribed previously. On comparison
of the externally standardized with
the internally standardized sets of
results on the 35 selected samples,
linear regression analysis showed ex-
cellent agreement between the two cal-
ibration procedures: Y(1S) = 1.073 ±
0.0229 * X(ext std) — 0.385 ± 0.468;
t - = 0.985; Sy.c = 1.54.
Matrix Spike Samples and Dupli-
cate Sample Assays. One matrix spike
for every 20 samples was prepared by
adding a known concentration of the
PFOA to the study subject serum sam-
ple for the purpose of assessment of
the method's accuracy throughout the
set of study subject serum samples.
The mean PFOA recovery for these
spiked samples was 95% with a stan-
dard deviation (SD) of 16.2%. In ad-
dition, one sample of every 10 was
extracted and analyzed in duplicate to
provide an assessment of the method's
precision throughout the set of sam-
ples. The average between assay %CV
for PFOA duplicates was 5.7%. The
lower limit of quantification of this
method is 0.5 ng/mL. Validation of
this LLOQ was conducted with repli-
cate spiked samples of human serum
with PFOA spiked into the samples at
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JOEM • Volume 48, Number 8, August 2006
0.5 ng/mL, the concentration of the
lowest calibrator for this assay. The
mean recovery ± SD was 101 ±
2.7%.
Serum (PFOA) Philadelphia Vol-
unteer Group. To help ensure that
published general population serum
PFOA levels were suitable for com-
parison purposes under the circum-
stances of the study, we identified a
comparison group of 30 volunteers
from the Philadelphia area. The Phila-
delphia volunteers, staff, and students
at the Hospital of the University of
Pennsylvania were paid $20 each to
participate. Their mean age was 34.3
years (range, 20-56 years); there were
nine men and 21 women. None iden-
tified previous or current occupational
exposure to PFOA. Blood from these
individuals was drawn, handled spun,
stored, shipped, and analyzed for
PFOA in an identical manner to the
blood obtained during the study. The
mean serum PFOA levels for the Phil-
adelphia comparison group was 6
ng/mL (interquartile range, 5-10 ng/
mL), consistent with published values
for the U.S. population.4-6
PFOA Water Sampling and
Comparison to Serum Levels
The concentration of PFOA in fin-
ished water in the Little Hocking
water system has been measured ap-
proximately quarterly from January
22, 2002, to March 18, 2005, by the
Ohio EPA. Fourteen measurements
were available for this period; results
before November 29, 2004, had been
reported as ammonium perfluo-
rooctanate (APFO) and as PFOA
from that date. PFOA concentration
in private residential well water was
publicly available for nine individu-
als for whom private well water was
their only reported source of residen-
tial drinking water. In one instance,
six samples had been taken at regular
intervals from 2002 through 2005. For
this well, the values obtained were
averaged to obtain a mean level over
the period. For the remaining wells,
only one sample had been analyzed
from a single point in time. The aver-
age PFOA concentration in Little Hock-
ing system distribution water from
January 2002 until May 2005 was 3.55
ng/mL (range, 1.5-7.2 ng/mQ). For
private wells used by study partici-
pants, PFOA concentrations ranged
from not detectable (<0.010 ng/mL)
to 14.0 ng/mL.
Statistical Analysis
To determine if serum PFOA lev-
els differed by dietary or personal
habits, water source, water use, oc-
cupational exposure, and so on, pre-
liminary data analyses included the t
test for binary predictors or the anal-
ysis of variance for greater than two
exposure categories. Adjustment for
multiple comparisons were made us-
ing Tukey-Kramer. To check the as-
sumptions of the statistical approach
used, various analyses were rerun
with the exact test using Monte
Carlo. Results were similar to that of
the F test. Subsequent higher -order
analyses included analysis of co-
variance adjusting for age. Final
multivariate analysis to assess the
independent contribution of multiple
variables was a generalized estimat-
ing equation (GEE) to adjust for
household cluster. Only variables as-
sociated with serum PFOA levels on
univariate analysis with a probability
<0.10 were included. To determine
model of best fit, both forced entry
and backward elimination were used.
All analyses were performed using
SAS statistical software (version 9.1;
SAS Institute, Cary, NC). A P <
0.05 was considered statistically sig-
nificant. Serum PFOA levels serum
(PFOA) are presented as mean, me-
dian, and interquartile range (IQR).
To examine the effect of demo-
graphic variables (age, gender, dura-
tion lived at current residence), we
excluded the 18 participants who re-
ported substantial occupational expo-
sure (defined subsequently) to PFOA.
To examine the effects of number of
glasses of drinking water per day, use
of a residential water filter, and of
dietary exposures, we included only
those residents whose sole source of
residential drinking water was Little
763
Hocking water system water. Only in-
dividuals who designated a single
source of residential drinking water
and who did not have substantial oc-
cupational exposure to PFOA were
included in these analyses.
Human Subjects Approval
The study was approved by the In-
stitutional Review Board of the Uni-
versity of Pennsylvania. The study was
voluntary and informed consent was
obtained for all participants before any
study. Minors under the ages of 17
were encouraged to give informed as-
sent whenever feasible. A certificate of
confidentiality was obtained from the
National Institutes of Health to ensure
maximum protection of personal infor-
mation and results.
A partnership among the University
of Pennsylvania School of Medicine,
The Decatur Community Association,
a local community association in the
Little Hocking water service area, and
Grand Central Family Medicine in
Parkersburg, West Virginia, a local
healthcare provider, conducted the
study through a grant from the Envi-
ronmental Justice Program of NIEHS.
The community was involved at all
stages of the study. A local healthcare
provider informed each participant of
his or her personal PFOA results to-
gether with any necessary explanation.
Results
Response and Participation Rate
Stratified Random Sample. Three
hundred forty-three individuals from
169 households participated in the
phlebotomy and questionnaire ad-
ministration. One subject withdrew
from the study, six subjects could not
donate sufficient blood, one subject
did not complete the questionnaire,
and 11 subjects did not meet eligibil-
ity criteria because their household
water service was received from a
water system other than ,the Little
Hocking Water Association. Accord-
ingly, data were available for analy-
sis from 324 subjects from 161
households selected through the
stratified random selection process.
DEQ-CFW 00000923

764 Community Exposure to Perfluorooctanoate • Emmett et al
TABLE 1
Household Participation Rates
for Randomly Selected Households
by Community
Households
Invited to
No. Agreeing
No. Completing
Participation
Participate
to Participate
Data Acquisition
Rate
Little Hocking
78
45
38
48.7
Belpre
17
8
7
41.2
Cutler
101
45
30
29.7
Vincent
241
115
86
35.7
Total
437
213
161
36.8
The participation rate by location of
household mailing address is given
in Table 1.
Response and Participation —
Community Volunteer Group. One
hundred percent of the 37 house-
holds selected by lottery participated
in the phlebotomy. However, two
individuals from two households did
not complete the questionnaire and
were excluded from further analysis.
Thus, data from 54 individuals from
35 households were included in the
final analysis. The racial and ethnic
composition of both participants and
volunteers was predominantly white
non -Hispanic (97% [N = 367]), re-
flecting, the composition of Washing-
ton County, Ohio.
Role of Occupational Exposure
We established criteria for substan-
tial occupational exposure to PFOA of
at least 1 year's work in a production
area within a facility in which PFOA
was used in the production process
with the last such occupational expo-
sure within the previous 10 years. Sev-
enteen individuals from the stratified
random sample and one from the local
volunteer sample met this definition
for substantial occupational exposure.
All had received their occupational
exposure to PFOA in the same flu-
oropolymer manufacturing facility lo-
cated in Washington, West Virginia,
across the Olio River from the study
area. An additional 48 individuals re-
ported past or current potential occu-
pational exposure to PFOA as follows
(individuals can be represented more
than once): 18 individuals had worked
in a fluoropolymer manufacturing fa-
cility in a nonproduction area at the
fluoropolymer production facility in a
production area for less than 1 year
total and/or more than 10 years ago or
in a job for another employer that
required visits to the fluoropolymer
production facility so did not meet the
criteria for substantial occupational ex-
posure; eight individuals had worked in
a job involving waste disposal or waste
processing from the fluoropolymer man-
ufacturing facility; 29 individuals had
worked as firefighters (volunteer, mili-
tary, as a company employee or paid);
and 13 individuals had worked in car-
pet cleaning, retreating carpets or rugs,
or in professional carpet installation.
Compared with the no -exposure
group, none of these occupational ex-
posure groups had statistically signifi-
cant elevated senim PFOA levels (P >
0.05) (Table 2). Among those with
potential occupational exposure, the
highest median values were observed
for firefighters. However, these values
remained well below the concentra-
tions of the substantial occupational
exposure group. Because none of these
groups had significantly elevated serum
PFOA levels, they were aggregated into
one group (potential exposure) for statis-
tical analysis purposes.
When comparing substantial, po-
tential, and no occupational exposure
groups, the substantial occupational
exposure group had a significantly
higher median serum PFOA levels of
775 ng/mL than the potential expo-
sure (388 ng/mL) and no occupa-
tional exposure groups (329 ng/mL)
(P = 0.0002 and P < 0.0001, respec-
tively, Table 2).
As a result of this finding, the sub-
stantial occupational exposure group
was removed from further analysis of
PFOA exposure in the community.
Because the serum PFOA levels for
the potential exposure group were not
different from the rest of the commu-
nity, they were included in subsequent
analyses of community exposures and
treated for purposes of analysis as res-
idents without substantial occupational
exposure.
Role of Community Air
Exposure: Serum (PFOA) by
Community of Residence
The median serum PFOA level in
the combined two areas with highest
potential air exposure (Little Hocking
and Belpre) was 326 ng/mL compared
with 368 ng/mL in the two combined
areas with a potentially minimal con-
tribution from PFOA through air pol-
lution (Cutler and Vincent) (Table 3).
This difference was not statistically
significant (P = 0.32).
Additionally, the inclusion of local
volunteers made no appreciable dif-
ference to the results (Table 3). Be-
cause of the similarity of serum
PFOA levels in each community re-
gardless of air pollution or the inclu-
sion of volunteers, all communities
and samples were combined in the
subsequent analyses to examine the
effects of water exposure on PFOA.
Role of Exposure in Water:
Serum PFOA and Primary
Source of Residential
Drinking Water
With regard to water exposure, the
highest median serum PFOA level
(374 ng/mL) was found for the group
who used only Little Hocking system
water as their residential drinking wa-
ter source (Table 4). The lowest was
found in those who currently used only
bottled and/or cistern and/or spring
water as the source of their residential
drinking water. The serum PFOA lev-
els in those who used bottled, spring,
or cistern water was significantly
lower than those in both the Little
Hocking water system only and the
DEQ-CFW 00000924

JOEM • Volume 48, Number 8, August 2006 765
TABLE 2
Serum (PFOA; ng/mQ by Occupational Exposure Group
Interquartile
Occupational Exposure N Median Mean Range
No occupational exposure
312
329
423
175-537
Potential occupational exposures`
48
388
406
168-623
Firefighter: voluntary, military, company employee, or paid
29
447
453
236-709
Nonproduction area of fluoropolymer facility, in production
18
381
386
125-430
area not meeting criteria for substantial occupational
exposure, or requiring visits to facility
Carpet cleaning, retreating carpets or rugs, or in profes-
13
302
408
191-631
sional carpet installation
Facility processing or disposing fluoropolymer production
8
253
578
115-918
waste
Substantial occupational exposure (production area within a
18
775
824
422-999
facility in which PFOA was used in the production
process >1 yr and last exposure having occurred within
previous 10 yrs)
'Some individuals had more than one potential occupational exposure, therefore, N for the potential occupational exposure subgroups does
not total to 48.
PFOA indicates perfluorooctanoate.
TABLE 3
Serum (perfluorooctanoate; ng/mL) by Community Area for Randomly Selected Participants and for All Participants'
All Participants (local volunteers and
Randomly Selected Participants randomly selected)
N Mean Median
IQR
N Mean Median IQR
Community areas with higher expected
contribution from air
Belpre
14
321
298
83-533
30
307
244
103-445
Little Hocking
74
478
327
187-572
92
458
311
175-567
Total
88
453
326
176-568
122
421
298
155-556
Community areas with minimal expected
contribution from air
Cutler
59
361
316
169-477
70
380
314
185-477
Vincent
160
439
370
190-570
168
438
370
188-577
Total
219
418
368
182-555
238
421
361
186-555
"Eighteen subjects with substantial occupational exposure were excluded from analysis.
IQR indicates interquartile range.
TABLE 4
Serum (PFOA; ng/mQ by Primary Residential Source of Drinking Water,
All
Participants (randomly selected and local volunteers)'t
Interquartile
Drinking Water Source N Median Mean
Range
Range
Little Hocking system water only 291 374 448
221-576
7-1950
Little Hocking system plus bottled 26 320 358
206-370
72-1280
or spring
Bottled and/or cistern and/or spring 10 71 154
49-217
12-527
only$
Well water and well and other 26 79 296
28-155
8-4520
`Subjects with substantial occupational exposure to PFOA were excluded from these
analyses.
tSeven subjects did not indicate residential source of drinking water.
tSignificantly different from Little Hocking water only (P = 0.003) and Little Hocking
system plus bottled or spring water (P = 0.05).
PFOA indicates perfluorooctanoate.
mixed Little Hocking plus another wa-
ter source groups (P = 0.0004 and
P = 0.007, respectively). The serum
PFOA levels for those who used Little
Hocking water system water only and
the mixed Little Hocking and another
water source were not statistically sig-
nificantly different (P = 0.17).
The mean scrim PFOA levels in
those who used any well water as their
sole residential drinking water source
was variable; this group included some
of the lowest and some of the highest
PFOA seam concentrations.
Relationship Between PFOA in
Primary Residential Water Supply
and Serum PFOA in Residents. Fig-
DEQ-CFW 00000925

766 Community Exposure to Perfluorooctanoate • Emmett et al
10000
C S 1000
O'0
LL
ao
2 E
0 100
Cn
10
Not Detectable .2-.3 3.55 5-15
Water PFOA (ppb)
Categorical scale
Fig. 2. Relationship of perfluorooetanoate (PFOA) concentration in water source (Little
Hocking and private wells) to serum PFOA levels. The numbers in parentheses indicate the
number of samples. Although the number of observations from persons using only residential
well water source is small, there is a marked and statistically significant relationship between the
PFOA levels in serum and the 'PFOA concentration in the residential drinking water source. Only
subjects 6 years of age or older using a single residential drinking water source were included in
the analysis.
1000
800
E 600
LO 400
L
a
200
2-5 6-10 11-15 16-20 21-30 31-40 41-50 51-60 >60
Age (years)
Fig. 3. Distribution of serum perfluorooetanoate (PFOA) levels (in ng/mL) by age. Residents
>60 years had significantly higher serum PFOA levels compared with all other age groups
except children aged 2-5 years.
ure 2 presents a graphic relationship
between PFOA concentrations in
drinking water and serum PFOA lev-
els. Three individuals drank from
wells where the PFOA was not de-
tectable; their average serum PFOA
level was 20.8 ng/mL (range, 13.6-
31.4 ng/mL). Six individuals used a
private well with measurable PFOA
in water as their only source of resi-
dential drinking water. Although the.
numbers of individuals for whom the
PFOA concentration in well water is
known is small, there is an apparent
strong relationship between the level
of the serum PFOA levels and the
PFOA concentration of the drinking
water source.
The median serum/drinking PFOA
water ratio residents using only the
Little Hocking water system was 105
(371/3.55) with an interquartile range
between 62 (221/3.55) and 162 (576/
3.55). For the six individuals who
used a private well with measured
PFOA as their only source of resi-
dential drinking water, the serum/
drinking water PFOA ratios ranged
from 142 to 855.
Serum PFOA Levels and Gender,
Age, Years of Residence, Smoking,
and Alcohol
Serum PFOA level was not sig-
nificantly different by gender for
participants without substantial oc-
cupational exposure (P = 0.32). The
median PFOA for females was 320
ng/mL (IQR, 161-509), and for
males, it was 345 (IQR, 190-576).
Serum PFOA concentrations were
highest in those aged more than 60,
followed by those aged from 2-5 and
those aged 51-60 (Fig. 3). Partici-
pants >60 years were significantly
more likely to have higher serum
PFOA levels compared with partici-
pants in all other age groups except
children 2 to 5 years old (0.0006 <
P < 0.02).
With regard to residence, only par-
ticipants over 18 years were exam-
ined. Years lived at current residence
was grouped into 2-5 years, 6-10
years, 11-15 years, and > 15 years.
Age was also found to be correlated
with years of residence (r = 0.6).
Therefore, age was controlled for in
the analysis for which no statistically
significant association between years
lived at current residence and serum
PFOA levels was found (P = 0.7).
The influence of alcohol cuusump-
tion (consumption of beer wine or
liquor in the last 30 days) and smoking
(current cigarette smoker) were evalu-
ated in all adult participants ages 18
and over who did not have substantial
occupational exposure. No significant
association was found between serum
PFOA levels and smoking (P = 0.28)
or serum PFOA levels and alcohol
consumption (P = 0.46).
Little Hocking Water System
Users: Water Use Variables
Affecting Serum
PFOA Concentrations
The effect of drinking tap water,
eating local fruits and vegetables, meat
DEQ-CFW 00000926

JOEM • Volume 48, Number 8, August 2006
TABLE 5
Serum (perfluorooctanoate; ng/mQ, Number of Tap Water Drinks per Day,
Consumption of Local Meat and Game, Fish, Vegetables, and Fruits, and Use of
Carbon Water Filter"
Interquartile
Factor N Meant Median Range pr > t
Tap water drinks/d
0
20
374
301
233-423 <0.0001
1-2
40
324
265
176-438
3-4
66
413
370
206-550
5-8
90
450
373
242-373
>8
55
565
486
294-486
Local meat
0
157
389
329
179-498 0.018
1-20
49
488
451
246-690
>20
77
516
424
295-595
Local fish
No
273
448
374
221-571 0.8958
Yes
18
458
398
290-681
Fruit and vegetables
from your garden
0
133
356
295
174-485 <0.0001
1-20
75
458
420
264-661
>20
77
571
469
308-802
Carbon water filter$
Yes
64
360
318
170-482 0.0005
No
209
493
421
258-631
"Little Hocking water source only.
tMeans adjusted for age unless otherwise indicated
$Not adjusted for age.
pr indicates probability.
t indicates t-value.
Tao
600
500
400
300
200
PFOA (ppb)
p=.46 p=.12 p=.96 p=.75 P=•19
1-5 6.12 >12 0 1 2-3 >3 0 1 2.3 >3 0 1 2-4 >4 0 1-9 >9
Cooking Making soups Reconstituting Reconstituting Home canning
vegetables and stews canned soups frozen juices vegetables
and pasta and meats
Fig. 4. Distribution of serum pe1-fluorooctanoate (PFOA) levels (in ng/mL) within household*
for cooking tap water uset (amounts are servings per week). *PFOA levels represents average
household value. tHouseholds using Little Hocking water system only.
or fish, or having a carbon water filter
on serum PFOA concentrations in Lit-
tle Hocking Water System Users is
shown in Table 5. With increasing tap
water drinks per day (at home or at
work), PFOA levels increased (P =
0.004). Particularly, participants who
drank eight or more cups of tap water
per day (at home or at work) had
significantly higher serum PFOA lev-
els compared with other drinking cat-
egories (0.002 < P < 0.004).
767
A secondary analysis has been per-
formed examining air exposure and
local vegetable/fruit intake. There was
no effect of air exposure on PFOA
(P = 0.16) or the interaction between
air exposure and local vegetable/fruit
intake (P = 0.73). As a result of the
lack of association between these two
variables, air exposure was not in-
cluded in the GEE model. Similarly,
there was a statistically significant in-
crease (P = 0.0002) in the mean serum
(PFOA) associated with increasing
numbers of weekly servings of fruits
and vegetables from a local garden.
Additionally, there was an increase in
serum PFOA with servings of meat or
game grown or harvested locally (P =
0.005). No association was found be-
tween local fish consumption and se-
rum PFOA concentrations.
With regard to water filtration sys-
tems, residents using only Little
Hocking water system water as their
residential drinking water source
were divided into two groups: those
using a home water filter system
based on carbon (N = 64), and those
who had no home water filtration
system or used a system not known
to remove PFOA or used a system
whose type and composition could
not be verified (N = 209). Residents
using carbon water filters had signif-
icantly lower median serum PFOA
levels (318 ng/mQ compared with
residents using Little Hocking System
water who did not use carbon water
filtration (421 ng/mQ (P = 0.008).
Serum PFOA Levels and
Household Cooking Use of
Tap Water
There was no relationship between
serum (PFOA) and the use of tap
water in cooking for those house-
holds using only Little Hocking wa-
ter system water (Fig. 4). When
cooking vegetables and pasta, mak-
ing soups and stews, reconstituting
canned soups, reconstituting frozen
fruit juices, and home canning of
vegetables and meats were exam-
ined, no statistically significant rela-
tionship with serum PFOA levels
DEQ-CFW 00000927

768 Community Exposure to Perfluorooctanoate • Emmett et all
TABLE 6
Results of Application of General Estimating Equations
Standard 95% Confidence
Parameter Estimate Error Limits Z pr > Z
Intercept
110.54
Vegetable and fruit from
62.31
your garden servings/wk
Tap water drinks/d
5.93
Age (yrs)
3.53
No carbon filter use
104.92
58.10 -3.34 224.42 1.9 0.0571
20.96 21.23 103.39 2.97 0.0029
2.02 1.97 9.88 2.94 0.0033
1.03 1.50 5.55 3.42 0.0006
35.86 34.65 175.20 2.93 0.0034
Note: This analysis includes only participants from households using Little Hocking water
system only. Participants with substantial occupational exposure were excluded.
pr indicates probability.
Z indicates Z-value.
was found. However, a linear trend
of increasing serum PFOA levels
was observed with increasing use of
water for making soups and stews
and for home canning of vegetables
and meats.
Little Hocking Water System
Users: Multivariate Analysis
Adjusting for
Household Clustering
The model of best -fit included age,
tap water drinks per day, fruit and vege-
table servings per week from your gar-
den, and use of a carbon filter (Table 6).
Eating meat and game grown or har-
vested locally was not found to be asso-
ciated with serum PFOA levels in the
multivariate analysis.
Discussion
We found that median serum
PFOA levels in randomly selected
residents of the Little Hocking water
service district ranged from 298 to
370 ng/mL, on the order of 60 to 75
times the median levels of approxi-
mately 5 ng/mL previously described
for general U.S. populations.4-6 The
majority of serum PFOA levels in
these residents exceeded the maxi-
mums reported in previous commu-
nity studies in other geographic
locations. For example, the range of
serum PFOA levels for 645 U.S.
adult blood donors was from 1.9
ng/mL to 52.3 ng/mL4; for 238 el-
derly volunteers in Seattle, it was 1.4
ng/mL to 16.7 ng/mL5; and for 598
children from across the United
States, it was from 1.9 ng/mL to 56.1
ng/mL.9 The serum PFOA levels for
the 30 comparison subjects for the
Philadelphia area in our study all fell
within previously reported normal
population ranges.
Our random sampling of residents
in the water district included a num-
ber of individuals who worked in the
production area of a fluoropolymer
manufacturing facility located across
the Ohio River in Washington, West
Virginia. This facility is believed to
be the primary source of PFOA pol-
lution in the area. A recent study of
workers at this plant found the median
serum PFOA level of 490 ng/mL for
259 workers currently working in pro-
duction areas where PFOA was
used.23 We found a median serum
PFOA level of 774 ng/mL for the 18
workers who had worked in the pro-
duction area at the facility, lived in the
Little Hocking water service area, and
participated in our study. The median
serum PFOA level for these 18 indi-
viduals was 284 ng/mL higher than the
median reported for all production
workers at the facility, suggesting a
combination of residential water and
occupational contributions to the
PFOA body burden. Because all but
one of the production workers we stud-
ied were selected through stratified
random sampling, we consider it un-
likely that selection bias could explain
this elevation. Workers from nonpro-
duction areas of the facility included in
our sampling did not have significantly
increased serum PFOA levels com-
pared with other residents. The serum
PFOA levels in nonoccupationally ex-
posed community residents in the
Little Hocking water service district
approached and frequently surpassed
those measured in production workers
exposed to PFOA at the source flu-
oropolymer manufacturing plant.
These results illustrate that body bur-
dens of pollutants sustained through
community environmental exposures
are not necessarily less than those sus-
tained through occupational exposure.
We were able to explore other po-
tential occupational exposure contribu-
tions to the serum PFOA levels. In
addition to use in the manufacture of
fluoropolymers, it has been suspected
that PFOA may also be a breakdown
product of fluorinated telomers. PFOA
is used as a surfactant or surface treat-
ment chemical in many products, in-
cluding firefighting foams; personal
care and cleaning products; oil, stain,
grease, and water repellent coatings on
carpet; textile leather; and paper.21
PFOA has had limited use as a fire
suppressant. A study of PFOA in con-
sumer products identified extractable
PFOA in carpet care solution -treated
cupeting.24 Because PFOA and re-
lated fluorinated compounds are cur-
rently unregulated, there is relatively
little available information on the ex-
tent of their use. Based on a qualitative
assessment of potential occupational
exposure to PFOA in the southeastern
Ohio area, we explored occupational
exposure in firefighting, carpet clean-
ing, and carpet installation in addition
to potential exposure in the disposal or
incineration of PFOA and/or waste
from the fluoropolymer manufacturing
facility. We did not observe a signifi-
cant increase in median serum PFOA
concentration in any of these occupa-
tional groups. It remains possible that
in a population with less exposure to
PFOA from ambient contamination,
identifiable contributions to the body
burden might be found from one or
more of these occupational exposures.
Several observations support the
conclusion that the major source of the
DEQ-CFW 00000928

JOEM • Volume 48, Number 8, August 2006
PFOA in Little Hocking water district
residents was drinking water. Serum
PFOA levels were similar whether res-
idents lived in the area proximate to
the plant where the air plume would
have been concentrated or in an area
that had the same water service but
was located up to 20 miles from the
plant and where air pollution with
PFOA was estimated to be minimal.
Serum PFOA levels were considerably
lower in those residents who were
currently using only bottled, spring, or
cistern water as their drinking water
source. Where the primary drinking
water source was well water, serum
PFOA levels varied in proportion with
well water PFOA levels.
The median serum/drinking water
PFOA ratio of 105 we observed in
Little Hocking water users likely re-
flects both high PFOA absorption
after oral ingestion and a long half-
life of PFOA in human blood. In rats,
the oral bioavailability of PFOA is
approximately 100%.25 The serum
half-life varies widely by species and
sex: several hours for female rats,
approximately 7 to 10 days for male
rats,25 and 20.9 days for male and
32.6 days for female cynomolgus
monkeys.26 The half-life in humans
appears to be much longer. In the one
set of data that is available, a study of
nine retirees from a fluoropolymer
production facility, the mean serum
PFOA half-life was found to be 4.4.
years.20 However, we did not find a
relationship between serum PFOA
levels and length of residence in the
Little Hocking water district among
study participants, all of whom had
lived in the area for at least 2 years.
If the half-life in the general commu-
nity is in the order of 4 to 5 years, we
would have expected to find a signif-
icant relationship with duration of
residence. Our results thus lead us to
question whether the serum PFOA
half-life in the general community is
as long as that published for the small
retired worker group.20 We expect to
have more data on this subject from a
follow-up study.
In residents who drank only Little
Hocking system water, the model of
best -tit for serum PFOA levels in-
cluded age, tap water drinks per day,
fruit and vegetable servings per week
from a local garden, and use of a
carbon water filter. The finding that
PFOA concentrations were higher in
children aged 5 and below and in the
elderly aged over 60 is disturbing,
because these may represent groups
particularly vulnerable to adverse
health consequences.27,28 The reason
for the higher serum PFOA levels in
those aged 60 and above is not en-
tirely clear; multivariate analysis
shows the increased consumption of
drinking water in this group does not
fully explain the observed increase.
Both the elderly and those aged 5
and below may spend more time at
home with exclusive use of residen-
tial water than working or school -
aged residents. Infants and young
children may have proportionately
greater exposure to water -borne pol-
lutants because they drink more wa-
ter per kilogram of body weight than
do adults.28 The levels in the very
young may also represent additional
exposures as PFOA has been shown
to cross the placenta and to be
present in breast milk (at approxi-
mately one tenth of the serum con-
centration) in Sprague Dawley rats,29
although comparable studies in hu-
mans are lacking. We are performing
further studies to elucidate PFOA
exposures in maternal milk and in-
fant formula. A higher serum PFOA
level for young children was previ-
ously observed by Olsen et a19 who
measured PFOA in the serum of 598
children aged 2 to 12 who partici-
pated in a nationwide U.S. study of
group A streptococcal infections,
645 adult blood donors from six U.S.
blood bank donation sites, and 238
elderly subjects in Seattle participat-
ing in a study of cognitive function.
The geometric mean serum PFOA
levels (4.6 ng/mL, 4.2 ng/mL, and
4.9 ng/mL, respectively) were simi-
lar in all groups. However, in the
children, there was a statistically sig-
nificant negative association with
age with the highest mean serum
PFOA levels noted at age 4 and the
769
lowest at age 12. Our failure to find
gender differences is consistent with
previous observations in the U.S.
general population.
The association with the number
of servings of fruits and vegetables
from the home garden was unex-
pected. Possible explanations include
the use of PFOA containing water
for cooking, canning, and washing
fruits and vegetables, PFOA in the
raw fruits and vegetables, and differ-
ent dietary and drinking habits in
those who consume more home-
grown fruits and vegetables. We
consider it unlikely that PFOA is
elevated in raw fruits and vegetables
from the garden because as a result
of the natural rainfall characteristics,
it is unusual to water gardens and
fruit trees extensively with residen-
tial water in this district. Also, the
association between serum PFOA
and servings of fruits and vegetables
was not reduced by adjusting for
residence in the areas with known
higher airborne and soil levels of
PFOA. We are undertaking further
studies to better understand the ob-
served association.
Individuals using carbon -type wa-
ter filters for residential drinking wa-
ter had a reduction of approximately
25% in median serum PFOA levels
compared with those not using a
filter. This reduction was much less
than we have seen for those who
drank only bottled, spring, or cistern
water. Because of limited effective-
ness, potential reliability problems as-
sociated with the need to maintain the
filter system, and potential health
problems associated with the use of
home filtration systems, we do not
recommend reliance on home filters to
remove PFOA. New water filtration
products to remove PFOA are cur-
rently being pilot -tested with prospects
of wider use in the near future.
The high serum PFOA levels in
our study as a result of the relatively
high exposure in drinking water may
have limited our ability to detect
relatively small increases associated
with contributions from ambient air
pollution. Thus, we cannot exclude
DEQ-CFW 00000929

770
the possibility that exposure to
PFOA in air could lead to a detect-
able contribution to the PFOA body
burden in other populations with
minimal water exposure.
Our finding that the major source
of serum PFOA was residential
drinking water has helped empower
those in the community who may
choose to lower their PFOA expo-
sure with a view to lowering their
body burden. As a result of our
preliminary findings that the levels
of PFOA were abnormally high in
residents of the Little Hocking water
district and that the major nonoccu-
pational PFOA source was residen-
tial drinking water, the option of free
bottled drinking water has been
made available through the Little
Hocking Water Association to those
with this water service. More than
half of the residents are already tak-
ing advantage of this offer. In addi-
tion, a new water filtration system
designed to remove PFOA is now
planned. We would anticipate that
these actions should result in reduced
serum PFOA levels. We plan to
monitor changes in serum PFOA lev-
els in the study group over the next
18 months to determine the extent of
any serum PFOA reductions.
Identification of water as the ma-
jor route of community exposure to
PFOA in this population should en-
courage efforts to define exposure
sources in other populations and
should provide a basis for personal
and regulatory efforts to reduce hu-
man exposure to a pollutant, which is
of concern because of remarkable
persistence in both the environment
and in humans.
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AH ed. Organofluorines. The Handbook
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lin: Springer-Verlag; 2002:63-83,
3. Kannan K, Koistinen J, Beckman K, et al.
Accumulation of perfluorooctane sulfo-
Community Exposure to Perfluorooctanoate • Emmett et al
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6. Olsen GW, Huang HY, Helzlsouer KJ,
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