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Polyfluoroalkyl chemicals in the U.S. population: Data from the National Health and Nutrition Survey (NHANES) 2003-2004 and comparisons with NHANES 1999-2000

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Abstract

Polyfluoroalkyl chemicals (PFCs) have been used since the 1950s in numerous commercial applications. Exposure of the general U.S. population to PFCs is widespread. Since 2002, the manufacturing practices for PFCs in the United States have changed considerably. We aimed to assess exposure to perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and eight other PFCs in a representative 2003-2004 sample of the general U.S. population >or= 12 years of age and to determine whether serum concentrations have changed since the 1999-2000 National Health and Nutrition Examination Survey (NHANES). By using automated solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry, we analyzed 2,094 serum samples collected from NHANES 2003-2004 participants. We detected PFOS, PFOA, PFHxS, and PFNA in > 98% of the samples. Concentrations differed by race/ethnicity and sex. Geometric mean concentrations were significantly lower (approximately 32% for PFOS, 25% for PFOA, 10% for PFHxS) and higher (100%, PFNA) than the concentrations reported in NHANES 1999-2000 (p < 0.001). In the general U.S. population in 2003-2004, PFOS, PFOA, PFHxS, and PFNA serum concentrations were measurable in each demographic population group studied. Geometric mean concentrations of PFOS, PFOA, and PFHxS in 2003-2004 were lower than in 1999-2000. The apparent reductions in concentrations of PFOS, PFOA, and PFHxS most likely are related to discontinuation in 2002 of industrial production by electrochemical fluorination of PFOS and related perfluorooctanesulfonyl fluoride compounds.
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VOLUME 115 | NUMBER 11 | November 2007
Environmental Health Perspectives
Research
Concern about exposure of the ecosystem,
including humans, to halogenated persistent
organic pollutants (POPs) has existed for sev-
eral decades. Many of these chemicals are per-
sistent and toxic, tend to bioaccumulate, and
can undergo long range atmospheric trans-
port; for these reasons, their production has
been banned or reduced worldwide, leading
to their decreased concentrations in the
ecosystem. In addition, adherence to provi-
sions set forth in the Stockholm Convention
on POPs for 12 organochlorine chemicals
(United Nations Environment Programme
2004) probably will result in continued
decreasing environmental concentrations.
More recently, the focus of environmental
and public health concern has shifted from
chlorinated chemicals to brominated and
fluorinated chemicals.
Among the fluorinated chemicals, the
polyfluoroalkyl chemicals (PFCs) have been
used extensively since the 1950s in commer-
cial applications, including surfactants, lubri-
cants, paper and textile coatings, polishes,
food packaging, and fire-retarding foams.
Some of these PFCs, including perfluoro-
octane sulfonic acid (PFOS) and perfluoro-
octanoic acid (PFOA), persist in humans and
the environment and have been detected
worldwide in wildlife (Houde et al. 2006 and
references therein). Exposure to PFOS and
PFOA in the general population also is wide-
spread, although demographic, geographic, and
temporal differences may exist (Calafat et al.
2006b, 2007; Fromme et al. 2007; Guruge
et al. 2005; Hansen et al. 2001; Harada et al.
2007; Kannan et al. 2004; Karrman et al.
2006; Olsen et al. 2005; Taniyasu et al. 2003;
Yeung et al. 2006).
No definite association has been estab-
lished between exposure to PFOS and PFOA
and adverse health effects in several occupa-
tional studies (Alexander et al. 2003; Gilliland
and Mandel 1993; Grice et al. 2007; Olsen
et al. 2004a) and in one population exposed
to PFOA through contaminated drinking
water (Emmett et al. 2006). Negative associa-
tions between cord serum concentrations of
both PFOS and PFOA and birth weight and
ponderal index, but not newborn length or
gestational age, have been reported in a
nonoccupational population (Apelberg et al.
2007). By contrast, no association has been
reported between employment in jobs with
high exposure to PFOS before the end of
pregnancy and maternally reported birth
weight (Grice et al. 2007). In animals, expo-
sure to PFOS and PFOA is associated with
adverse health effects (Kennedy et al. 2004;
Lau et al. 2004; Organisation for Economic
Co-operation and Development 2002) albeit
at serum concentrations orders of magnitude
higher than the concentrations observed in
the general population (Butenhoff et al.
2004; Luebker et al. 2005). Because of these
compounds’ known toxicity to animals, their
ubiquitous presence, and their persistence in
humans, wildlife, and the environment, PFCs
research is of interest to toxicologists, epi-
demiologists, and environmental and public
health scientists.
Biomonitoring data for these PFCs in the
general population are needed to assess cur-
rent exposures and to determine whether
technologic changes affect human exposures
to these compounds. As part of the continu-
ous U.S. National Health and Nutrition
Examination Survey (NHANES), urine and
serum samples are collected and analyzed for
selected environmental chemicals [Centers for
Disease Control and Prevention (CDC)
2005]. NHANES participants also provide
sociodemographic information and medical
history and undergo standardized physical
examinations (CDC 2003). We recently
reported the concentrations of PFOS, PFOA,
and nine other PFCs in 1,562 participants
from NHANES 1999–2000 (Calafat et al.
2007). The high frequency of detection of
PFOS and PFOA suggested highly prevalent
exposures to these compounds at a time when
both were being manufactured in the United
States. In 2002, the 3M Company (St. Paul,
MN), the sole U.S. producer of PFOS, dis-
continued its production of PFOS and
related perfluorooctanesulfonyl fluoride
Address correspondence to A.M. Calafat, Division of
Laboratory Sciences, National Center for
Environmental Health, Centers for Disease Control
and Prevention, 4770 Buford Hwy, NE, Mailstop
F53, Atlanta, GA 30341, USA. Telephone: (770) 488-
7891. Fax: (770) 488-4371. E-mail: Acalafat@cdc.gov
Supplemental Material is available online at
http://www.ehponline.org/docs/2007/10598/suppl.pdf
The authors thank J. Pirkle for useful discussions,
and J. Tully, K. Kato, A. Wanigatunga, and
J. Ekong for technical assistance.
The findings and conclusions in this article are
those of the authors and do not necessarily represent
the views of the Centers for Disease Control and
Prevention.
The authors declare they have no competing
financial interests.
Received 25 June 2007; accepted 29 August 2007.
Polyfluoroalkyl Chemicals in the U.S. Population: Data from the National
Health and Nutrition Examination Survey (NHANES) 2003–2004 and
Comparisons with NHANES 1999–2000
Antonia M. Calafat, Lee-Yang Wong, Zsuzsanna Kuklenyik, John A. Reidy, and Larry L. Needham
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
BACKGROUND: Polyfluoroalkyl chemicals (PFCs) have been used since the 1950s in numerous
commercial applications. Exposure of the general U.S. population to PFCs is widespread. Since
2002, the manufacturing practices for PFCs in the United States have changed considerably.
O
BJECTIVES: We aimed to assess exposure to perfluorooctane sulfonic acid (PFOS), perfluorooc-
tanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and
eight other PFCs in a representative 2003–2004 sample of the general U.S. population 12 years
of age and to determine whether serum concentrations have changed since the 1999–2000 National
Health and Nutrition Examination Survey (NHANES).
M
ETHODS: By using automated solid-phase extraction coupled to isotope dilution–high-perfor-
mance liquid chromatography–tandem mass spectrometry, we analyzed 2,094 serum samples col-
lected from NHANES 2003–2004 participants.
R
ESULTS: We detected PFOS, PFOA, PFHxS, and PFNA in > 98% of the samples. Concentrations
differed by race/ethnicity and sex. Geometric mean concentrations were significantly lower (approx-
imately 32% for PFOS, 25% for PFOA, 10% for PFHxS) and higher (100%, PFNA) than the con-
centrations reported in NHANES 1999–2000 (p < 0.001).
C
ONCLUSIONS: In the general U.S. population in 2003–2004, PFOS, PFOA, PFHxS, and PFNA
serum concentrations were measurable in each demographic population group studied. Geometric
mean concentrations of PFOS, PFOA, and PFHxS in 2003–2004 were lower than in 1999–2000.
The apparent reductions in concentrations of PFOS, PFOA, and PFHxS most likely are related to
discontinuation in 2002 of industrial production by electrochemical fluorination of PFOS and
related perfluorooctanesulfonyl fluoride compounds.
K
EY WORDS: biomonitoring, C8, exposure, PFCs, PFOA, PFOS, prevalence, serum. Environ
Health Perspect 115:1596–1602 (2007). doi:10.1289/ehp.10598 available via http://dx.doi.org/
[Online 29 August 2007]
(POSF)–based chemistries by electrochemical
fluorination. Although PFOA and its salts
and precursors still are manufactured by oth-
ers by a different process, reductions in their
manufacturing emissions have been proposed
[Prevedouros et al. 2006; U.S. Environmental
Protection Agency (EPA) 2006]. We now
report the serum concentrations of 12 PFCs,
including PFOS and PFOA, in 2,094 partici-
pants from NHANES 2003–2004 and com-
pare these data with data from NHANES
1999–2000 (Calafat et al. 2007). The
2003–2004 data provide the first estimates of
serum PFC concentrations in a representative
U.S. population since implementation of the
changes in manufacturing practices for some
PFCs in the United States.
Materials and Methods
We obtained serum samples analyzed for
PFCs from 2,094 participants 12 years of
age from NHANES 2003–2004. The
National Centers for Health Statistics
Institutional Review Board reviewed and
approved the study protocol. All participants
provided informed written consent; parents
or guardians provided consent for participants
< 18 years of age (CDC 2006a).
We measured perfluorooctane sulfonamide
(PFOSA), 2-(N-ethyl-perfluorooctane sulfon-
amido) acetic acid (Et-PFOSA-AcOH), 2-(N-
methyl-perfluorooctane sulfonamido) acetic
acid (Me-PFOSA-AcOH), perfluorobutane
sulfonic acid (PFBuS), perfluorohexane sul-
fonic acid (PFHxS), PFOS, PFOA, perfluoro-
heptanoic acid (PFHpA), perfluorononanoic
acid (PFNA), perfluorodecanoic acid (PFDeA),
perfluoroundecanoic acid (PFUA), and per-
fluorododecanoic acid (PFDoA) in 1 mL of
serum, using a modification of the method of
Kuklenyik et al. (2004), which involved auto-
mated solid-phase extraction coupled to
reversed-phase high-performance liquid chro-
matography–tandem mass spectrometry. We
used
18
O
2
-PFOS (for all sulfonic acids and all
amides) and
13
C
2
-PFOA (for all carboxylic
acids) for quantification. To compensate for
the lack of isotope-labeled internal standards
for the other analytes and to partially account
for matrix effects, the calibration standards
were spiked into calf serum. The limits
of detection (LODs) ranged from 0.1 to
1.0 µg/L; the accuracy ranged from 84 to
135% at three concentrations (Kuklenyik et al.
2004); and the precision ranged from around
10 to 26% at two different levels (Table 1).
Low-concentration (~ 3 µg/L to ~ 9 µg/L) and
high-concentration (~ 10 µg/L to ~ 30 µg/L)
quality-control (QC) materials, prepared from
a base calf serum pool, were analyzed with
reagent blank, serum blank, and NHANES
samples (Kuklenyik et al. 2004). Standard,
blank, QC, and NHANES samples were
analyzed by the procedure described above.
We analyzed the data using SAS (version
9.1.3; SAS Institute Inc., Cary, NC) and
SUDAAN (version 9.0.1; Research Triangle
Institute, Research Triangle Park, NC).
SUDAAN calculates variance estimates after
incorporating the sample population weights,
designed for the one-third subset of the full sur-
vey, which account for unequal selection proba-
bilities and planned oversampling of certain
subgroups resulting from the complex multi-
stage area probability design of NHANES.
Race/ethnicity was defined on the basis of self-
reported data as non-Hispanic black, non-
Hispanic white, and Mexican American.
Persons not defined by these groups were
included only in the total population estimate.
Age was reported in years at the most recent
birthday. We estimated the weighted percent-
age of detection and calculated weighted geo-
metric means and percentiles for the serum
concentrations (in micrograms per liter) of the
various PFCs. For concentrations below the
LOD, as recommended for the analysis of
NHANES data (CDC 2006b), we used a value
equal to the LOD divided by the square root
of 2 (Hornung and Reed 1990). Parametric
statistics were computed only for analytes for
which the frequency of detection was 60%.
Because PFC concentrations were not normally
distributed, we used the natural log transforma-
tion. Weighted Pearson correlation coefficients
and related p-values were calculated in SAS.
Statistical significance was set at p < 0.05.
We used analysis of covariance to examine
the influence of demographic and socioeco-
nomic variables on the log-transformed serum
concentrations of PFOS, PFOA, PFHxS, and
PFNA. For multiple regression, we calculated
the least square geometric means (LSGM) and
compared them for each categorical variable.
The variables included in the initial model were
as follows: age as a continuous variable, sex,
race/ethnicity, smoking status (yes/no), and
education (less than high school, high school
diploma, more than high school). Participants
were categorized as smokers if their serum coti-
nine concentrations were > 10 µg/L. We chose
to include education in the model without
household income to minimize the possibility
of collinearity because a) income and education
are strongly associated (chi-square p = 0.001)
and b) the final model yielded comparable
results with either variable separately (except for
PFOS, which included one additional signifi-
cant term between income and smoking status).
We assessed all possible two-way interaction
terms in the model.
To reach the final reduced model, we
used backward elimination with a threshold
of p < 0.05 for retaining the variable in the
model, using Satterwaite adjusted F statistics.
We evaluated for potential confounding by
adding each of the excluded variables back
into the final model one by one and examin-
ing changes in the β coefficients of the statis-
tically significant main effect. If addition of
one of these excluded variables caused a
change in a β coefficient by 10%, the vari-
able was re-added to the model.
Results
The distribution of PFC serum concentra-
tions is reported stratified by age, sex, and
race/ethnicity (Tables 2–5). Four analytes
were detected in > 98% of the samples
(PFOS, 99.9%; PFOA, 99.7%; PFHxS,
98.3%; PFNA, 98.8%). Concentrations of
these four PFCs ranged from < 0.4 µg/L to
435 µg/L (PFOS), < 0.1 µg/L to 77.2 µg/L
(PFOA), < 0.3 µg/L to 82.0 µg/L (PFHxS),
and < 0.1 µg/L to 11.5 µg/L (PFNA). Six
other analytes were detected at lower frequen-
cies: PFDeA (31.3%), Me-PFOSA-AcOH
(27.5%), PFOSA (22.2%), PFUA (9.7%),
Polyfluoroalkyl chemicals in the United States in 2003–2004
Environmental Health Perspectives
VOLUME 115 | NUMBER 11 | November 2007
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Table 1. LOD and precision data for the 12 polyfluoroalkyl compounds included in this study and a compar-
ison of these parameters to the previously reported data for NHANES 1999-2000.
Precision
a
LOD (µg/L)
b
QCL QCH
NHANES NHANES NHANES NHANES NHANES NHANES
Analyte 2003–2004 1999–2000 2003–2004 1999–2000 2003–2004 1999–2000
PFOSA 0.2 0.05 2.7 (14.9) 2.4 (14.1) 13.0 (16.3) 12.4 (12.5)
Me-PFOSA-AcOH 0.6 0.2 3.4 (15.5) 3.1 (14.2) 9.1 (16.7) 9.0 (13.5)
Et-PFOSA-AcOH 0.4 0.2 3.8 (17.2) 3.5 (14.3) 8.3 (19.2) 8.1 (15.6)
PFBuS 0.4 ND 4.4 (18.2) ND 14.6 (15.1) ND
PFHxS 0.3 0.1 2.5 (16.4) 2.1 (16.6) 11.9 (12.9) 11.2 (12.3)
PFOS 0.4 0.2 8.9 (10.4) 8.8 (8.4) 31.4 (10.1) 31.6 (7.1)
PFHpA 0.3 0.4 7.6 (17.0) 6.8 (13.5) 15.8 (14.3) 15.5 (12.0)
PFOA 0.1 0.1 3.2 (10.0) 3.1 (8.5) 14.7 (10.9) 15.1 (7.3)
PFNA 0.1 0.1 2.5 (15.0) 2.6 (15.4) 12.7 (13.2) 13.0 (10.9)
PFDeA 0.3 0.2 2.4 (17.5) 2.2 (13.9) 8.5 (18.2) 8.4 (13.1)
PFUA 0.3 0.2 1.9 (22.0) 2.0 (19.1) 9.9 (19.8) 10.6 (16.2)
PFDoA 1.0 0.2 2.2 (25.6) 2.4 (22.4) 8.5 (25.7) 9.1 (19.3)
ND, not determined.
a
Mean concentration (% coefficient of variation) of repeated measurements (minimum of 20) over time of quality-control
calf serum materials of low (QCL) and high (QCH) concentrations.
b
The NHANES 1999–2000 samples were analyzed by
using the approach described in Kuklenyik et al. (2005), whereas the NHANES 2003–2004 samples were analyzed by using
the Kuklenyik et al. (2004) approach.
PFHpA (6.2%), and Et-PFOSA-AcOH,
(3.4%); their geometric mean and selected
percentile concentrations are given as
Supplemental Material in Tables S1–S6
(online at http://www.ehponline.org/docs/
2007/10598/suppl.pdf). For the two analytes
detected in < 1% of the samples (PFDoA,
< 0.1%; PFBuS, 0.4%), we could not calcu-
late the 95th percentile of concentrations.
Statistically significant correlations (p <
0.001) existed between the log-transformed
concentrations of PFOS and PFOA (Pearson
correlation coefficient r = 0.66), PFHxS (r =
0.56), and PFNA (r = 0.50); between PFOA
and PFHxS (r = 0.46) and PFNA (r = 0.55);
and between PFHxS and PFNA (r = 0.17).
The final models included sex (p < 0.01),
age, race/ethnicity, and age-by-race/ethnicity
interaction (p = 0.01) for PFOS; sex, race/
ethnicity, age, education, sex-by-age (p <
0.01), sex-by-race/ethnicity (p = 0.03), and
education-by-age (p = 0.04) interactions for
PFOA; sex, race/ethnicity (p = 0.01), age, and
sex-by-age interaction (p = 0.02) for PFHxS;
and sex (p < 0.01), race/ethnicity, age, educa-
tion (p = 0.02), smoking status (p = 0.02),
and race/ethnicity-by-age (p < 0.01) and
Calafat et al.
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VOLUME 115 | NUMBER 11 | November 2007
Environmental Health Perspectives
Table 2. Geometric mean and selected percentiles (95% confidence intervals) of perfluorooctanesulfonate (PFOS) concentrations in serum (µg/L) for the
U.S. population 12 years of age and older: data from NHANES 2003–2004.
Variable Geometric mean 10th percentile 25th percentile 50th percentile 75th percentile 90th percentile 95th percentile No.
All 20.7 (19.2–22.3) 9.8 (9.0–10.8) 14.6 (13.8–15.2) 21.1 (19.8–22.4) 29.9 (27.5–32.8) 41.2 (35.5–48.9) 54.6 (44.0–65.9) 2,094
12–19 years 19.3 (17.5–21.4) 9.9 (9.5–10.9) 14.4 (12.5–15.7) 19.9 (17.6–21.9) 27.1 (23.6–30.2) 36.5 (28.6–45.6) 42.2 (35.1–52.1) 640
20–39 years 18.7 (17.3–20.1) 8.9 (8.2–10.2) 12.6 (11.2–14.2) 18.7 (17.7–20.4) 27.4 (24.9–29.7) 36.9 (33.6–41.3) 44.3 (38.6–60.8) 490
40–59 years 22.0 (19.7–24.5) 10.6 (9.2–12.3) 15.3 (14.1–18.0) 22.2 (20.2–24.2) 32.2 (27.4–35.4) 43.8 (33.5–62.7) 61.5 (43.8–81.8) 387
60 years 23.2 (20.8–25.9) 9.9 (7.7–13.0) 16.6 (15.0–17.9) 23.9 (20.9–27.2) 34.7 (30.0–39.3) 50.3 (40.8–68.9) 69.4 (49.6–90.0) 577
Mexican American 14.7 (13.0–16.6) 7.4 (5.6–7.9) 10.3 (8.3–11.8) 15.9 (13.4–17.9) 21.1 (18.7–23.5) 28.1 (24.1–35.0) 35.5 (28.9–38.5) 485
Non-Hispanic black 21.6 (19.1–24.4) 9.9 (7.5–11.9) 14.8 (12.5–16.8) 22.0 (19.5–24.9) 32.2 (28.1–36.2) 43.8 (37.2–57.3) 57.5 (43.8–78.4) 538
Non-Hispanic white 21.4 (19.9–23.1) 10.5 (9.5–11.5) 15.0 (14.4–16.0) 21.9 (20.5–23.0) 30.2 (27.7–33.0) 41.3 (35.7–49.6) 55.9 (44.0–69.4) 962
Female 18.4 (17.0–20.0) 9.0 (7.8–9.9) 12.4 (11.5–13.8) 18.2 (16.8–19.7) 27.3 (23.6–30.0) 39.7 (34.4–42.6) 45.7 (42.3–61.5) 1,041
Male 23.3 (21.1–25.6) 12.3 (10.4–13.5) 17.7 (15.9–18.9) 23.9 (22.3–25.3) 32.1 (28.7–35.7) 45.3 (35.5–62.7) 62.7 (43.8–81.8) 1,053
Table 3. Geometric mean and selected percentiles (95% confidence intervals) of perfluorooctanoate (PFOA) concentrations in serum (µg/L) for the U.S. population
12 years of age and older: data from NHANES 2003–2004.
Variable Geometric mean 10th percentile 25th percentile 50th percentile 75th percentile 90th percentile 95th percentile No.
All 3.9 (3.6–4.3) 1.9 (1.8–2.1) 2.7 (2.6–3.0) 4.0 (3.8–4.4) 5.8 (5.2–6.3) 7.8 (6.7–9.6) 9.8 (7.4–14.1) 2,094
12–19 years 3.9 (3.5–4.4) 2.2 (1.9–2.3) 2.9 (2.6–3.2) 3.9 (3.3–4.4) 5.4 (4.6–6.1) 6.9 (5.6–9.2) 8.6 (5.9–12.6) 640
20–39 years 3.9 (3.6–4.2) 1.8 (1.5–2.1) 2.7 (2.5–3.0) 4.1 (3.7–4.5) 5.8 (5.4–6.1) 7.6 (7.3–8.4) 9.6 (8.4–11.1) 490
40–59 years 4.2 (3.8–4.8) 2.0 (1.8–2.4) 2.9 (2.6–3.2) 4.2 (3.9–4.8) 6.3 (5.3–7.2) 8.2 (6.8–10.7) 10.6 (7.4–16.9) 387
60 years 3.7 (3.3–4.1) 1.8 (1.5–2.1) 2.7 (2.4–2.9) 3.9 (3.5–4.3) 5.4 (4.9–5.9) 7.2 (6.0–9.5) 9.5 (6.9–14.1) 577
Mexican American 3.1 (2.8–3.4) 1.4 (1.1–1.8) 2.2 (1.9–2.5) 3.3 (3.0–3.6) 4.4 (4.1–5.1) 6.7 (5.7–7.3) 7.6 (6.7–10.5) 485
Non-Hispanic black 3.4 (3.0–3.8) 1.2 (1.1–1.6) 2.2 (1.9–2.5) 3.7 (3.1–4.2) 5.1 (4.4–6.1) 7.7 (5.3–10.9) 9.3 (6.5–13.9) 538
Non-Hispanic white 4.2 (3.9–4.5) 2.1 (2.0–2.3) 3.0 (2.6–3.2) 4.2 (3.9–4.6) 5.9 (5.4–6.6) 7.8 (7.2–9.1) 9.8 (7.6–13.3) 962
Female 3.5 (3.2–3.8) 1.6 (1.5–1.9) 2.5 (2.2–2.7) 3.6 (3.2–3.9) 5.2 (4.6–5.7) 7.1 (6.3–8.2) 8.4 (7.4–10.6) 1,041
Male 4.5 (4.1–4.9) 2.3 (2.0–2.4) 3.2 (3.1–3.5) 4.6 (4.2–5.0) 6.3 (5.6–7.1) 8.3 (6.8–11.8) 10.4 (7.4–17.5) 1,053
Table 4. Geometric mean and selected percentiles (95% confidence intervals) of perfluorohaxanesulfonate (PFHxS) concentrations in serum (µg/L) for the
U.S. population 12 years of age and older: data from NHANES 2003–2004.
Variable Geometric mean 10th percentile 25th percentile 50th percentile 75th percentile 90th percentile 95th percentile No.
All 1.9 (1.7–2.2) 0.7 (0.6–0.7) 1.0 (0.9–1.2) 1.9 (1.6–2.1) 3.3 (2.8–3.9) 5.9 (4.8–7.2) 8.3 (7.1–9.7) 2,094
12–19 years 2.4 (2.1–2.9) 0.6 (0.5–0.8) 1.2 (1.0–1.4) 2.3 (1.7–3.0) 4.8 (3.9–6.0) 9.5 (6.8–12.5) 13.1 (9.9–19.6) 640
20–39 years 1.8 (1.6–2.0) 0.5 (0.5–0.6) 1.0 (0.9–1.2) 1.7 (1.5–2.0) 2.8 (2.5–3.3) 4.8 (3.9–6.1) 6.7 (4.9–9.4) 490
40–59 years 1.9 (1.6–2.2) 0.7 (0.5–0.8) 1.0 (0.9–1.2) 1.6 (1.4–2.0) 3.1 (2.3–4.5) 5.5 (4.3–6.9) 6.7 (5.5–8.2) 387
60 years 2.0 (1.7–2.4) 0.8 (0.5–0.9) 1.1 (1.0–1.3) 1.9 (1.6–2.1) 3.2 (2.6–3.7) 7.2 (4.3–9.7) 10.2 (7.0–12.6) 577
Mexican American 1.4 (1.2–1.7) 0.5 (0.3–0.7) 0.7 (0.5–0.9) 1.4 (1.2–1.7) 2.3 (1.9–2.7) 4.2 (3.1–5.1) 5.4 (4.0–8.9) 485
Non-Hispanic black 1.9 (1.6–2.3) 0.5 (0.3–0.7) 1.1 (0.9–1.3) 1.9 (1.5–2.2) 3.4 (2.7–4.3) 6.0 (5.0–7.1) 8.2 (6.3–12.0) 538
Non-Hispanic white 2.0 (1.8–2.3) 0.7 (0.6–0.8) 1.1 (1.0–1.3) 1.9 (1.6–2.1) 3.3 (2.8–4.0) 6.0 (4.6–7.8) 8.1 (6.9–10.1) 962
Female 1.7 (1.6–1.9) 0.6 (0.5–0.6) 0.9 (0.8–1.0) 1.5 (1.4–1.8) 2.9 (2.5–3.5) 5.8 (4.6–6.9) 8.2 (6.7–10.0) 1,041
Male 2.2 (1.9–2.5) 0.8 (0.7–1.0) 1.3 (1.1–1.4) 2.0 (1.8–2.4) 3.3 (2.8–4.4) 6.1 (4.6–8.1) 8.5 (6.4–10.5) 1,053
Table 5. Geometric mean and selected percentiles (95% confidence intervals) of perfluorononanoate (PFNA) concentrations in serum (µg/L) for the U.S. popula-
tion 12 years of age and older: data from NHANES 2003–2004.
Variable Geometric mean 10th percentile 25th percentile 50th percentile 75th percentile 90th percentile 95th percentile No.
All 1.0 (0.8–1.1) 0.4 (0.3–0.4) 0.6 (0.5–0.6) 1.0 (0.9–1.1) 1.5 (1.2–1.7) 2.2 (1.6–3.8) 3.2 (1.8–7.7) 2,094
12–19 years 0.9 (0.7–1.0) 0.3 (0.3–0.4) 0.5 (0.5–0.6) 0.7 (0.6–0.9) 1.2 (0.9–1.5) 1.9 (1.2–3.3) 2.7 (1.3–6.3) 640
20–39 years 1.0 (0.8–1.1) 0.3 (0.2–0.5) 0.6 (0.6–0.7) 0.9 (0.8–1.1) 1.4 (1.2–1.7) 2.1 (1.7–2.7) 2.8 (1.9–6.1) 490
40–59 years 1.1 (0.9–1.4) 0.5 (0.4–0.5) 0.7 (0.6–0.7) 1.0 (0.9–1.2) 1.7 (1.2–2.4) 2.7 (1.6–5.9) 4.3 (1.7–9.3) 387
60 years 0.8 (0.7–1.0) 0.3 (0.2–0.3) 0.5 (0.5–0.6) 0.9 (0.8–1.0) 1.3 (1.1–1.5) 1.9 (1.5–3.0) 3.0 (1.6–6.5) 577
Mexican American 0.7 (0.6–0.8) 0.2 (0.1–0.2) 0.5 (0.4–0.5) 0.7 (0.5–0.8) 1.0 (0.9–1.3) 1.6 (1.2–1.8) 2.0 (1.6–2.8) 485
Non-Hispanic black 1.1 (0.8–1.5) 0.4 (0.3–0.6) 0.6 (0.5–0.8) 1.0 (0.8–1.4) 1.6 (1.2–2.7) 3.1 (1.5–6.5) 4.7 (2.1–9.3) 538
Non-Hispanic white 1.0 (0.8–1.1) 0.4 (0.3–0.4) 0.5 (0.5–0.6) 0.8 (0.8–0.9) 1.5 (1.2–1.7) 2.2 (1.6–3.4) 2.9 (1.8–6.2) 962
Female 0.9 (0.7–1.0) 0.4 (0.3–0.4) 0.6 (0.5–0.6) 0.9 (0.7–0.9) 1.2 (1.0–1.6) 2.2 (1.4–3.3) 3.0 (1.7–6.1) 1,041
Male 1.1 (0.9–1.3) 0.5 (0.4–0.5) 0.6 (0.6–0.7) 1.0 (0.9–1.2) 1.6 (1.3–1.8) 2.4 (1.7–4.8) 4.0 (1.8–8.7) 1,053
Polyfluoroalkyl chemicals in the United States in 2003–2004
Environmental Health Perspectives
VOLUME 115 | NUMBER 11 | November 2007
1599
age-by-smoking status (p = 0.04) interactions
for PFNA. Because of these interactions with
age, concentrations were compared at the
25th (age = 26 years), 50th (age = 41 years),
75th (age = 55 years), and 90th (age = 70
years) percentiles of age.
LSGM concentrations provide geometric
mean estimates for a demographic variable
after adjustment for the model covariates
(Table 6). The statistical significance values
when comparing these LSGM concentrations
are shown in the Supplemental Material,
Table S7 (online at http://www.ehponline.
org/docs/2007/10598/suppl.pdf). PFOS
LSGM concentrations were significantly
higher (p < 0.01) in males than in females.
Similarly, for PFOA and PFHxS, males had
significantly higher LSGM concentrations
than females except at the 90th percentile of
age (Table 6). LSGM concentrations of
PFHxS were significantly lower for Mexican
Americans than for non-Hispanic blacks (p =
0.01) and non-Hispanic whites (p < 0.01);
LSGM concentrations did not differ signifi-
cantly between non-Hispanic whites and
non-Hispanic blacks (p = 0.49). PFOS and
PFNA LSGM concentrations were signifi-
cantly lower in Mexican Americans than in
non-Hispanic blacks (PFOS, p < 0.01; PFNA,
p < 0.01–0.03) and non-Hispanic whites
(PFOS, p < 0.01; PFNA, p < 0.01–0.02),
regardless of age; LSGM concentrations
between non-Hispanic whites and non-
Hispanic blacks differed significantly only at
the 75th and 90th percentiles of age (Table
6). Non-Hispanic whites had significantly
higher PFOA LSGM concentrations (p <
0.01), regardless of sex, than Mexican
Americans. The differences between Mexican-
American males and non-Hispanic black
males and between non-Hispanic white males
and non-Hispanic black males were not statis-
tically significant.
We used a two-sample t-test to compare
the difference of the two geometric mean
concentrations (on the log scale) of PFOS,
PFOA, PFHxS, and PFNA during NHANES
1999–2000 and NHANES 2003–2004
(Table 7), taking into account their associated
standard errors and degrees of freedom, by
age, sex, and race/ethnicity, using SAS. The
differences were all statistically significant
(p < 0.05), except for PFHxS in Mexican
Americans (p = 0.21) (Table 7). We analyzed
the NHANES 2003–2004 samples first and
then the NHANES 1999–2000 samples
(Calafat et al. 2007) using two methods that
differed in the manner in which PFCs were
extracted and preconcentrated from the
serum (Kuklenyik et al. 2004, 2005). In both
methods, we used tandem mass spectrometry
with
18
O
2
-PFOS,
13
C
2
-PFOA, and
18
O
2
-
PFOSA (only for NHANES 1999–2000) for
quantification, the same multiple reaction
monitoring transitions for quantification for
PFOA (413/369) and PFOS (499/99), the
same QC materials and analytical standards.
18
O
2
-PFOSA was not commercially available
when the 2003–2004 NHANES samples
were analyzed. Except for PFNA and PFOA,
for which the LODs were the same regardless
of the method, the method used for
NHANES 1999–2000 (Kuklenyik et al.
2005) had slightly lower LODs than the
method used for NHANES 2003–2004
(Kuklenyik et al. 2004) (Table 1). To esti-
mate whether method differences could
account for the differences in concentrations,
we analyzed QC samples from low and high
concentration pools and 124 split samples
using both methods. The two methods
showed good agreement from the results of
the split sample analysis [presented for PFOA
in Figures S1 and S2 in Supplemental
Table 6. Least-square geometric mean concentrations (µg/L) (95% confidence intervals) of PFOA, PFOS,
PFHxS, and PFNA in various demographic groups.
Group PFOA PFOS PFHxS PFNA
Female 18.5 (17.1–20) 0.9 (0.7–1)
Male 23.6 (21.8–25.7) 1.1 (0.9–1.3)
Female: age P25 3.4 (3.1–3.7) 1.7 (1.5–1.9)
Female: age P50 3.5 (3.3–3.8) 1.7 (1.5–1.9)
Female: age P75 3.7 (3.4–4) 1.7 (1.5–2)
Female :age P90 3.8 (3.4–4.2) 1.7 (1.5–2)
Male: age P25 5.1 (4.7–5.5) 2.4 (2–2.8)
Male: age P50 4.5 (4.2–4.9) 2.2 (1.9–2.6)
Male: age P75 4.1 (3.7–4.5) 2.1 (1.8–2.4)
Male: age P90 3.7 (3.2–4.2) 1.9 (1.6–2.3)
MA 1.4 (1.1–1.7)
NHB 1.9 (1.6–2.3)
NHW 2.0 (1.8–2.3)
Female, MA 2.6 (2.3–3)
Female, NHB 2.8 (2.5–3.2)
Female, NHW 3.8 (3.5–4.1)
Male, MA 3.6 (3.3–3.9)
Male, NHB 4.1 (3.5–4.8)
Male, NHW 4.6 (4.2–5.1)
MA: age P25 13.9 (12.5–15.5) 0.7 (0.6–0.8)
MA: age P50 15.1 (13.6–16.8) 0.7 (0.6–0.8)
MA: age P75 16.3 (14.4–18.4) 0.7 (0.5–0.8)
MA: age P90 17.7 (15.3–20.6) 0.6 (0.5–0.8)
NHW: age P25 20.1 (18.6–21.8) 1 (0.8–1.2)
NHW: age P50 21.2 (19.6–22.9) 1 (0.8–1.1)
NHW: age P75 22.3 (20.5–24.3) 0.9 (0.8–1.1)
NHW: age P90 23.5 (21.3–26) 0.9 (0.8–1)
NHB: age P25 19.9 (17.9–22.1) 1.1 (0.8–1.4)
NHB: age P50 22.6 (20.1–25.5) 1.2 (0.9–1.6)
NHB: age P75 25.5 (22.1–29.5) 1.3 (1–1.9)
NHB: age P90 29.0 (24.3–34.7) 1.5 (1–2.1)
NonSMK: age P25 1 (0.8–1.1)
NonSMK: age P50 1 (0.8–1.1)
NonSMK: age P75 1 (0.8–1.1)
NonSMK: age P90 1 (0.8–1.2)
SMK: age P25 1.1 (0.9–1.3)
SMK: age P50 1 (0.8–1.1)
SMK: age P75 0.9 (0.8–1)
SMK: age P90 0.8 (0.7–1)
< HS 0.7 (0.6–0.8)
= HS 1 (0.8–1.1)
> HS 1.2 (0.9–1.7)
< HS: age P25 3.7 (3.4–4.1)
< HS: age P50 3.7 (3.4–4.1)
< HS: age P75 3.7 (3.3–4.1)
< HS: age P90 3.7 (3.3–4.2)
= HS: age P25 4.4 (4.1–4.7)
= HS: age P50 4 (3.7–4.3)
= HS: age P75 3.7 (3.3–4.1)
= HS: age P90 3.3 (2.8–4)
> HS: age P25 4.2 (3.8–4.6)
> HS: age P50 4.1 (3.7–4.5)
> HS: age P75 4.1 (3.6–4.6)
> HS: age P90 4 (3.4–4.7)
Abbreviations: HS, high school; MA, Mexican American; NHB, non-Hispanic black; NHW, non-Hispanic white; NonSMK,
nonsmoker; P25, 25th percentile of age = 26 years; P50, 50th percentile of age = 41 years; P75, 75th percentile of age = 55
years; P90, 90th percentile of age = 70 years; SMK, smoker.
Calafat et al.
1600
VOLUME 115 | NUMBER 11 | November 2007
Environmental Health Perspectives
Material (online at http://www.ehponline.
org/docs/2007/10598/suppl.pdf)]. Results
were similar for all other analytes (data not
shown). In general, analysis of the QC pools
showed mean concentrations and coefficients
of variation which were similar between the
two methods (Table 1).
Discussion
We detected PFOS, PFOA, PFHxS, and
PFNA in > 98% of persons in this representa-
tive sample of the civilian, noninstitutional-
ized U.S. population, 12 years of age. These
findings confirm that measurable serum con-
centrations of these compounds were preva-
lent in the United States in 2003–2004, even
after 3M in 2002 discontinued its industrial
production of PFOS and related compounds,
including the ammonium salt of PFOA.
Direct and indirect sources of PFOA still exist
in the United States, although since 1999,
global emissions of PFOA reportedly have
decreased by more than half as of 2004
(Prevedouros et al. 2006), and current pro-
ducers have committed to reducing manufac-
turing emissions of PFOA and its salts and
precursors (U.S. EPA 2006).
Other PFCs, however, were detected
infrequently. For example, PFBuS was
detected in < 0.5% of the samples. PFBuS is a
final degradation product of perfluorobutane-
sulfonyl fluoride, now used in the manufac-
ture of materials as a replacement for
POSF-related chemicals [C-6 (e.g., PFHxS)
and C-8 (e.g., PFOS)] that were phased out
beginning in 2000. Similarly, in a study
involving 18 volunteer employees from 3M
Company, PFBuS was detected only in work-
ers with production-related duties, whereas
PFOA, PFOS, and PFHxS were detected in
most workers (Ehresman et al. 2007). The
lower frequency of detection of PFBuS than
PFOS, PFOA, and PFHxS suggests that
human exposures to PFBuS are indeed lower,
and/or that pharmacokinetic factors, which
might include increased urinary elimination,
are different.
PFOS showed the highest geometric
mean and 95th percentile concentrations, fol-
lowed by PFOA, PFHxS, and PFNA. For
PFOS, PFOA, and PFNA, however—unlike
lipophilic POPs whose serum concentrations
increase with age (Needham et al. 2006)—
concentrations were quite similar among the
four age groups (Tables 2–5), a finding that
agrees with previous data (Calafat et al. 2007;
Olsen et al. 2003, 2004b, 2004c). By con-
trast, for PFHxS, the geometric mean and
95th percentile concentrations were higher
for adolescents than for adults, as previously
reported (Calafat et al. 2007; Olsen et al.
2004b). The higher concentrations of PFHxS
in children and adolescents could be related
to their increased contact with carpeted floors
containing PFHxS, which is used for specific
postmarket carpet-treatment applications
(Olsen et al. 2004b).
In agreement with previous reports
(Calafat et al. 2006a, 2007; Fromme et al.
2007; Harada et al. 2004; Midasch et al.
2006; Yeung et al. 2006), we observed sex and
race/ethnicity differences. Females had signifi-
cantly lower LSGM concentrations of PFOS
than did males (Table 6). For PFOA and
PFHxS, sex differences also existed but were
not as pronounced for the elderly (Table 6).
Mexican Americans had the lowest LSGM
concentrations of PFHxS and non-Hispanic
whites and non-Hispanic blacks had similar
concentrations (Table 6). Racial differences
for PFOS and PFNA were age dependent,
whereas those for PFOA were sex dependent
(Table 6). These sex and racial differences may
reflect variability in exposure patterns as a
result of differences in factors such as lifestyle,
diet, and use of products containing PFCs
that may contribute to the observed serum
concentrations of PFCs.
To evaluate whether the discontinued pro-
duction of PFOS and related compounds by
3M Company in 2002 and technologic
changes implemented by other companies have
led to a subsequent decrease in serum PFC
concentrations in the general U.S. population
(Olsen et al. 2007b), we compared NHANES
data of 1999–2000 with NHANES data of
2003–2004. The distribution of serum con-
centrations of PFOS, PFOA, PFHxS, and
PFNA by sex, race/ethnicity, and age in
2003–2004 (Tables 2–5) was similar to that
for the general U.S. population in 1999–2000
(Calafat et al. 2007). However, the geometric
mean concentrations for PFOS, PFOA, and
PFHxS in 2003–2004 were lower than for
1999–2000. For PFNA, 2003–2004 levels
were higher than those found in 1999–2000.
These concentrations differed significantly for
all demographic groups except for PFHxS in
Mexican Americans (Table 7). Various con-
centration percentiles similarly decreased for
PFOS, PFOA, and PFHxS. We analyzed the
NHANES 1999–2000 and 2003–2004 sam-
ples by using two different methods; however,
these approaches provided equivalent results
[Table 1; Figures S1 and S2 in the Supple-
mental Material (online at http://www.
ehponline.org/docs/2007/10598/suppl.pdf)],
indicating that the differences cannot be
attributed to changes in the analytical
methodology. The decrease in serum concen-
trations of PFOS and PFOA during this time
interval agreed with the reported reductions in
PFOS and PFOA concentrations for a group
of Red Cross blood donors in the United
States (Olsen et al. 2007b) and in PFOS (tem-
poral trends for PFOA were not examined) in
Arctic ringed seals in the same time (Butt et al.
2007). These decreases in serum concentra-
tions of PFOS and PFOA in humans and
wildlife had been related to the phaseout of
POSF-based materials in 2000–2002 (Butt
et al. 2007; Olsen et al. 2007b).
For PFHxS, although the geometric mean
concentrations were lower in 2003–2004
than in 1999–2000, the differences were less
evident, and in some cases they reversed at the
higher concentration percentiles for some
demographic categories. These findings may
be related to the lower concentrations of
PFHxS than of PFOS or PFOA and to differ-
ences in the estimated geometric mean serum
Table 7. Geometric mean concentrations (95% confidence intervals) of PFOA, PFOS, PFHxS, and PFNA in NHANES 1999–2000 and NHANES 2003–2004 for the
whole population and different demographic groups.
a
PFOS PFOA PFHxS PFNA
Variable 1999–2000 2003–2004 1999–2000 2003–2004 1999–2000 2003–2004 1999–2000 2003–2004
All 30.4 (27.1–33.9) 20.7 (19.2–22.3) 5.2 (4.7–5.7) 3.9 (3.6–4.3) 2.1 (1.9–2.4) 1.9 (1.7–2.2) 0.5 (0.5–0.7) 1.0 (0.8–1.1)
12–19 years 29.1 (26.2–32.4) 19.3 (17.5–21.4) 5.5 (5.0–6.0) 3.9 (3.5–4.4) 2.7 (2.1–3.4) 2.4 (2.1–2.9) 0.5 (0.4–0.5) 0.9 (0.7–1.0)
20–39 years 27.5 (24.9–30.2) 18.7 (17.3–20.1) 5.2 (4.7–5.7) 3.9 (3.6–4.2) 2.0 (1.7–2.3) 1.8 (1.6–2.0) 0.5 (0.4–0.6) 1.0 (0.8–1.1)
40–59 years 33.0 (28.0–38.8) 22.0 (19.7–24.5) 5.4 (4.7–6.2) 4.2 (3.8–4.8) 2.1 (1.8–2.3) 1.9 (1.6–2.2) 0.6 (0.4–0.7) 1.1 (0.9–1.4)
60 years 33.3 (28.5–38.8) 23.2 (20.8–25.9) 4.8 (4.3–5.5) 3.7 (3.3–4.1) 2.2 (1.9–2.5) 2.0 (1.7–2.4) 0.6 (0.5–0.8) 0.8 (0.7–1.0)
Female 28.0 (24.6–31.8) 18.4 (17.0–20.0) 4.8 (4.3–5.3) 3.5 (3.2–3.8) 1.8 (1.6–2.1) 1.7 (1.6–1.9) 0.5 (0.4–0.6) 0.9 (0.7–1.0)
Male 33.4 (29.6–37.6) 23.3 (21.1–25.6) 5.7 (5.2–6.3) 4.5 (4.1–4.9) 2.6 (2.3–3.0) 2.2 (1.9–2.5) 0.6 (0.5–0.7) 1.1 (0.9–1.3)
Mexican American 22.7 (19.8–25.9) 14.7 (13.0–16.6) 3.9 (3.6–4.2) 3.1 (2.8–3.4) 1.5 (1.1–1.9) 1.4 (1.2–1.7) 0.3 (0.3–0.4) 0.7 (0.6–0.8)
Non-Hispanic black 33.0 (26.2–41.6) 21.6 (19.1–24.4) 4.8 (4.1–5.6) 3.4 (3.0–3.8) 2.2 (1.6–2.9) 1.9 (1.6–2.3) 0.8 (0.6–1.0) 1.1 (0.8–1.5)
Non-Hispanic white 32.0 (29.1–35.2) 21.4 (19.9–23.1) 5.6 (5.0–6.2) 4.2 (3.9–4.5) 2.3 (2.0–2.5) 2.0 (1.8–2.3) 0.6 (0.5–0.7) 1.0 (0.8–1.1)
a
For PFOS, PFOA, and PFNA, all differences between NHANES 1999–2000 (Calafat et al. 2007) and NHANES 2003–2004 geometric mean concentrations are statistically significant (
p
<
0.001). For PFHxS, except for Mexican Americans (
p
= 0.209), all other differences are also statistically significant with
p
< 0.001, except for females (
p
= 0.037), persons 60 years of age
(
p
= 0.016), persons 12–19 years of age (
p
= 0.004), and non-Hispanic blacks (
p
= 0.004).
elimination half-life (PFHxS, 7.3 years;
PFOA, 3.5 years; and PFOS, 4.8 years)
(Olsen et al. 2007a). Furthermore, the corre-
lation between the serum concentrations of
PFOS and PFOA was higher than correla-
tions of PFHxS and either PFOA or PFOS,
suggesting potential common exposure path-
way(s) for PFOA and PFOS, but probably
not for PFHxS (mostly used in carpet-treat-
ment applications (Olsen et al. 2004b).
Pharmacokinetic factors may also contribute
to these differences. The transformation of
certain POFS-related sulfonamides to PFOS
and potentially to PFOA in the atmosphere
was suggested as a common mechanism for
formation of both PFOS and PFOA, which
would account at least partly for the high cor-
relation in serum concentrations (Olsen et al.
2007b). On the other hand, PFOA and other
perfluorocarboxylates (e.g., PFNA), but not
PFOS, might be formed from the biodegrada-
tion of the volatile fluorotelomer alcohols
(Ellis et al. 2004).
Current manufacturing practices exclu-
sively use fluorotelomers for the synthesis of
perfluorocarboxylates (Prevedouros et al.
2006). Perfluorocarboxylates, including
PFNA, were present as reaction by-products
in POSF-based materials (Prevedouros et al.
2006). Interestingly, our data suggest that
PFNA geometric mean concentrations in
2003–2004 approximately doubled over those
of 1999–2000. However, because human
exposure data for PFNA are more limited than
they are for PFOS, PFOA, and even PFHxS,
these results must be interpreted with caution.
In 2004, the estimated annual production of
the ammonium salt of PFNA, primarily used
as a processing aid in the manufacture of such
fluoropolymers as polyvinylidene fluoride, was
15–75 tonnes (Prevedouros et al. 2006).
Information about efforts to reduce manufac-
turing emissions for PFNA, estimated at about
10% of the amount produced, was not found
(Prevedouros et al. 2006). As a comparison,
global manufacturing emissions of PFOA were
about 15 tonnes in 2004, down from about
45 tonnes in 1999 (Prevedouros et al. 2006).
For most PFCs, these NHANES
2003–2004 results are consistent with reduced
population exposure because of recent efforts
of industry and government. U.S. and world-
wide efforts continue in attempts to reduce
exposures to PFCs, including PFOS and
PFOA, and many halogenated POPs, includ-
ing polybrominated diphenyl ethers. We will
continue to assess exposure to these and other
chemicals in the U.S. population through
NHANES, an effort that will provide unique
information on trends of exposure to these
chemicals over time. In addition, we are
analyzing pooled serum samples from 3- to
11-year-old children to fill data gaps for mean
PFC concentrations in this age range.
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Environmental Health Perspectives
... The bioavailability of PFOA, crossing biological barriers, is indicated by the detection of PFOA in blood and mothers' milk samples (Awad et al. 2020;Calafat et al. 2007;Tao et al. 2008;Völkel et al. 2008;Ye et al. 2018). The major route of exposure to PFOA in humans comes from ingestion of contaminated food and drinking water Sadia et al. 2020;Stahl et al. 2011;Trudel et al. 2008). ...
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... Individual PFAS may also be by-products of commercially relevant PFAS uses, which include transformation products of precursor compounds as well as breakdown products from consumer and industrial goods. Because of widespread use, as well as their mobility and persistence, most humans have detectable internal PFAS contamination from multiple sources, notably food, food contact materials, and indoor products [3]. Near-ubiquitous "background" levels of blood contamination have been detected in a United States nationally-representative population. ...
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... 4,5 These chemicals, which are present in food, food packaging, and many everyday consumer products, have been detected in more than 98% of U.S. population serum samples. 6 In addition, an estimated 200 million Americans consume water with PFAS concentrations exceeding 1 ng=L, one of several health-based limits under regulatory consideration 7 (currently there is no national drinking water standard for PFAS). ...
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Research Perfluorooctanesulfonate [PFOS; CF 3 (CF 2) 7 SO 3 – ] and its acid salts were derived from perfluorooctanesulfonyl fluoride [POSF; CF 3 (CF 2) 7 SO 2 F]. Major product applications were developed using POSF through formation of N-alkylsulfonamides that were used in surfactants, paper and pack-aging treatments, and surface protectants (e.g., carpet, upholstery, textiles). Depending on the specific functional derivitization or polymerization, these POSF-based products may have degraded or metabolized, to an undetermined degree, to PFOS, a stable and persistent end product that has a widespread presence in the general population (Butenhoff et al. 2006) and wildlife (Houde et al. 2006). Salts of perfluorooctanoic acid, in particular ammonium perfluorooctanoate (APFO), have been used as surfactants and processing aids in the production of fluoropolymers and fluoro-elastomers. Industrial production of the salts of perfluorooctanoic acid occur through electro-chemical fluorination and telomerization. Perfluorooctanoate [PFOA; CF 3 (CF 2) 6 COO – ], the dissociated carboxylate anion, has been measured in humans worldwide but generally at lower nanogram per milliliter concentrations than PFOS (Houde et al. 2006). In rats, PFOS and PFOA are not metabo-lized and enter into the enterohepatic circula-tion (Johnson et al. 1984; Kemper 2003; Kuslikis et al. 1992; Vanden Heuvel et al. 1991). Because of the stability of the carbon– fluorine bond and the high electronegativity of perfluorinated alkyl acids, metabolism would not be favored; thus, perfluorohexanesulfonate (PFHS) is also not expected to be metabolized. Based on the determination of volumes of distribution from single-dose intravenous stud-ies in cynomolgus monkeys, the distributions of PFOS, PFHS, and PFOA are primarily extracellular (Butenhoff et al. 2004; Noker and Gorman 2003a, 2003b). Kerstner-Wood et al. (2003) found PFOS, PFHS, and PFOA to be highly bound in rat, monkey, and human plasma over a concentration range of 1–500 µg/mL. When incubated with human plasma protein fractions, all three compounds were highly bound (99.7 to > 99.9%) to albu-min, and showed affinity for β-lipoproteins (95.6, 64.1, and 39.6% for PFOS, PFHS, and PFOA, respectively). Some binding to α-and γ-globulin fractions and minor interactions with transferrin (PFHS and PFOA) were also noted. PFOS and PFOA have been shown to compete for fatty acid binding sites on liver fatty acid binding protein, with PFOS giving the stronger response (Luebker et al. 2002). The elimination rates of PFOS and PFHS have been studied in male and female cynomolgus monkeys after intravenous dosing (Noker and Gorman 2003a, 2003b) and for PFOS after repeated oral dosing (Seacat et al. 2002). Noker and Gorman (2003a, 2003b) reported mean (± SD) terminal elimination half-lives, ranging from 88 to 146 days (132 ± 13 days for males and 110 ± 26 days for females) for PFOS and 49 to 200 days (141 ± 52 days for males and 87 ± 47 days for females) for PFHS, after intravenous dosing of three male and three female cynomolgus mon-keys in separate experiments, with no signifi-cant difference between males and females or between the two compounds. Seacat et al. (2002) reported an approximate terminal elimination half-life of 200 days for PFOS in male and female cynomolgus monkeys dur-ing 1 year immediately following 6 months of daily oral dosing with either 0.15 or 0.75 mg/kg PFOS. Elimination rates in species other than the monkey have been determined for PFOS and PFOA. Within 89 days after a single intra-venous dose of 14 C-PFOS, 30% of the 14 C was excreted in the urine and 12% in the feces of male rats (Johnson et al. 1979). For PFOA, significant interspecies differences have been observed (Hundley et al. 2006; Kudo and Kawashima 2003), and differential expression of organic anion transporters in renal proxi-mal tubule cells have been suggested as an
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Perfluorooctanesulfonyl fluoride (POSF)-based materials include surfactants, paper and packaging treatments, and surface (e.g., carpet, upholstery, textile) protectants. A metabolite, perfluorooctanesulfonate (PFOS, C8F17SO-3), has been identified in the serum and liver tissue of nonoccupationally exposed adults and wildlife. Results from several repeat-dose toxicological studies consistently demonstrate that the liver is the primary target organ with an apparent threshold for the toxic effects of PFOS that can be expressed in terms of cumulative dose or body burden. The purpose of this study was to characterize the distribution of PFOS and six other fluorochemicals in 598 serum samples obtained from a multi-center study of children (ages 2-12) diagnosed with group A streptococcal infections. Using high-pressure liquid chromatography tandem mass spectrometry methods, serum PFOS concentrations ranged from 6.7 ppb (ng/mL) to 515 ppb (geometric mean 37.5 ppb, 95% CI 36.0-39.1) with an estimate of the 95th percentile (i.e., upper tolerance limit) of 89 ppb (upper 95% confidence limit 97 ppb). Serum perfluorooctanoate (PFOA) concentrations were approximately an order of magnitude lower than PFOS. Unlike comparable adult data reported elsewhere for PFOS and PFOA, children had substantially higher estimates for the 95th percentile for perfluorohexanesulfonate (65 ppb) and N-methyl perfluorooctanesulfonamidoacetate (12 ppb) (upper 95% confidence limits of 81 ppb and 15 ppb, respectively). The reasons for these dissimilarities in a subgroup of children remain to be determined. Different exposure and activity patterns between children and adults should be considered.
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In the attempt to estimate the average concentration of a particular contaminant during some period of time, a certain proportion of the collected samples is often reported to be below the limit of detection. The statistical terminology for these results is known as censored data, i.e., nonzero values which cannot be measured but are known to be below some threshold.Samples taken over time are assumed to follow a lognormal distribution. Given this assumption, several techniques are presented for estimation of the average concentration from data containing nondetectable values. The techniques proposed include three methods of estimation with a left-censored lognormal distribution: a maximum likelihood statistical method and two methods involving the limit of detection. Each method is evaluated using computer simulation with respect to the bias associated with estimation of the mean and standard deviation. The maximum likelihood method was shown to produce unbiased estimates of both the mean and standard deviation under a variety of conditions. However, this method is somewhat complex and involves laborious calculations and use of tables. Two simpler alternatives involve the substitution of L/2 and a new proposal of L/2 for each nondetectable value, where L = the limit of detection. The new method was shown to provide more accurate estimation of the mean and standard deviation than the L/2 method when the data are not highly skewed. The L/2 method should be used when the data are highly skewed (geometric standard deviation [GSD] approximately 3.0 or greater)
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Perfluorooctanoic acid (PFOA) has been found at low levels (10 to 100 parts per billion) in sera of the general population and at higher levels in occupationally exposed workers. Although PFOA has been reported to be a promoter of rodent hepatocarcinogenesis and to alter reproductive hormones in humans and rodents, there is little information on human health effects associated with PFOA exposure. The present study examined the relationship between PFOA and mortality using a retrospective cohort mortality design. The cohort consisted of 2788 male and 749 female workers employed between 1947 and 1983 at a plant that produced PFOA. The all-causes standardized mortality ratio was .75 (95% confidence interval [CI], .56 to .99) for women and .77 (95% CI, .69 to .86) for men. Among men the cardiovascular standardized mortality rate was .68 (95% CI, .58 to .80) and the all-gastrointestinal diseases was .57 (95% CI, .29 to .99). There was no significantly increased cause-specific standardized mortality ratio for either men or women. Ten years of employment in exposed jobs was associated with a 3.3-fold increase (95% CI, 1.02 to 10.6) in prostate cancer mortality compared to no employment in PFOA production. There were only six prostate cancer deaths overall and four among the exposed workers; thus, the results must be interpreted cautiously. If prostate cancer mortality is related to PFOA, PFOA may increase prostate cancer mortality by altering reproductive hormones in male workers.
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Since the early 1980s, there has been a steady increase in the use of nonvolatile fluorinated organic compounds for a variety of industrial and commercial applications. The industrial use of these relatively stable compounds has initiated debate over the fate of fluorochemicals in the environment and, ultimately, the bioavailability of these compounds. In this manuscript, we present quantitative results from a study of 65 human sera samples purchased from biological supply companies that provide characterization of specific organic fluorochemicals present in the sera of nonindustrially exposed humans. Summed together, the compound-specific characterization data reported here agree closely with levels of nonspeciated organic fluorine that were originally reported to be present in sera in 1970. The compound-specific method for the extraction of extremely low levels of several commercial organic fluorochemicals from sera and liver with quantitative detection by negative ion electrospray tandem mass spectrometry described represents a robust, previously undescribed approach to quantifying specific organic fluorochemicals in biological matrices.
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Occurrence of perfluorooctane sulfonate (PFOS) in the tissues of humans and wildlife is well documented. In this study, concentrations and distribution of PFOS, perfluorohexane sulfonate (PFHS), and perfluorobutane sulfonate (PFBS) were determined in samples of surface water, fish and bird blood and livers, and human blood collected in Japan. Notable concentrations of PFOS were found in surface water and fish from Tokyo Bay. PFOS was found in all of the 78 samples of fish blood and liver analyzed. Based on the concentrations of PFOS in water and in fish livers, bioconcentration factors were calculated to range from 274 to 41 600. Concentrations of PFOS in the blood of Japanese human volunteers ranged from 2.4 to 14 ng/mL. PFHS was detected in 33% of the fishes analyzed, at concentrations severalfold less than those of PFOS.
Article
To evaluate the mortality experience of a cohort of employees of a perfluorooctanesulphonyl fluoride (POSF) based fluorochemical production facility. A retrospective cohort mortality study followed all workers with at least one year of cumulative employment at the facility. The jobs held by cohort members were assigned to one of three exposure subgroups; high exposed, low exposed, and non-exposed, based on biological monitoring data for perfluorooctane sulphonate (PFOS). A total of 145 deaths were identified in the 2083 cohort members. Sixty five deaths occurred among workers ever employed in high exposed jobs. The overall mortality rates for the cohort and the exposure subcohorts were lower than expected in the general population. Two deaths from liver cancer were observed in the workers with at least one year of high or low exposure (standardised mortality ratio (SMR) 3.08, 95% CI 0.37 to 11.10). The risk of death from bladder cancer was increased for the entire cohort (three observed, SMR 4.81, 95% CI 0.99 to 14.06). All three bladder cancers occurred among workers who held a high exposure job (SMR 12.77, 95% CI 2.63 to 37.35). The bladder cancer cases primarily worked in non-production jobs, including maintenance and incinerator and wastewater treatment plant operations. Workers employed in high exposure jobs had an increased number of deaths from bladder cancer; however it is not clear whether these three cases can be attributed to fluorochemical exposure, an unknown bladder carcinogen encountered during the course of maintenance work, and/or non-occupational exposures. With only three observed cases the possibility of a chance finding cannot be ruled out.
Article
Perfluorooctanesulfonyl fluoride (POSF, C8F17SO2F) related-materials have been used as surfactants, paper and packaging treatments, and surface (e.g., carpet, textile, upholstery) protectants. A metabolite, perfluorooctanesulfonate (PFOS, C8F17SO3-), has been identified in the serum and liver of non-occupationally exposed humans and wildlife. Because of its persistence, an important question was whether elderly humans might have higher PFOS concentrations. From a prospective study designed to examine cognitive function in the Seattle (WA) metropolitan area, blood samples were collected from 238 dementia-free subjects (ages 65-96). High-pressure liquid chromatography-electrospray tandem mass spectrometry determined seven fluorochemicals: PFOS; N-ethyl perfluorooctanesulfonamidoacetate; N-methyl perfluorooctanesulfonamidoacetate; perfluorooctanesulfonamidoacetate; perfluorooctanesulfonamide; perfluorooctanoate; and perfluorohexanesulfonate. Serum PFOS concentrations ranged from less than the lower limit of quantitation (3.4 ppb) to 175.0 ppb (geometric mean 31.0 ppb; 95% CI 28.8-33.4). An estimate of the 95% tolerance limit was 84.1 ppb (upper 95% confidence limit 104.0 ppb). Serum PFOS concentrations were slightly lower among the most elderly. There were no significant differences by sex or years residence in Seattle. The distributions of the other fluorochemicals were approximately an order of magnitude lower. Similar to other reported findings of younger adults, the geometric mean serum PFOS concentration in non-occupational adult populations likely approximates 30-40 ppb with 95% of the population's serum PFOS concentrations below 100 ppb.