1596 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 several decades. Many of these chemicals are persistent and toxic, tend to bioaccumulate, and

can undergo long range atmospheric transport; for these reasons, their production has

been banned or reduced worldwide, leading

to their decreased concentrations in the

ecosystem. In addition, adherence to provisions 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 commercial applications, including surfactants, lubricants, paper and textile coatings, polishes,

food packaging, and fire-retarding foams.

Some of these PFCs, including perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic 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 widespread, 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 established between exposure to PFOS and PFOA

and adverse health effects in several occupational 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 associations 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, exposure 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, epidemiologists, and environmental and public

health scientists.

Biomonitoring data for these PFCs in the

general population are needed to assess current exposures and to determine whether

technologic changes affect human exposures

to these compounds. As part of the continuous 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, discontinued 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.

OBJECTIVES: 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 ≥ 12 years

of age and to determine whether serum concentrations have changed since the 1999–2000 National

Health and Nutrition Examination Survey (NHANES).

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.

KEY 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 others 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 participants from NHANES 2003–2004 and compare 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 sulfonamido) acetic acid (Et-PFOSA-AcOH), 2-(Nmethyl-perfluorooctane sulfonamido) acetic

acid (Me-PFOSA-AcOH), perfluorobutane

sulfonic acid (PFBuS), perfluorohexane sulfonic acid (PFHxS), PFOS, PFOA, perfluoroheptanoic acid (PFHpA), perfluorononanoic

acid (PFNA), perfluorodecanoic acid (PFDeA),

perfluoroundecanoic acid (PFUA), and perfluorododecanoic acid (PFDoA) in 1 mL of

serum, using a modification of the method of

Kuklenyik et al. (2004), which involved automated solid-phase extraction coupled to

reversed-phase high-performance liquid chromatography–tandem mass spectrometry. We

used 18O2-PFOS (for all sulfonic acids and all

amides) and 13C2-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 survey, which account for unequal selection probabilities and planned oversampling of certain

subgroups resulting from the complex multistage area probability design of NHANES.

Race/ethnicity was defined on the basis of selfreported data as non-Hispanic black, nonHispanic 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 percentage of detection and calculated weighted geometric 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 transformation. 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 socioeconomic 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 cotinine 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 significant 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 examining changes in the β coefficients of the statistically significant main effect. If addition of

one of these excluded variables caused a

change in a β coefficient by ≥ 10%, the variable was re-added to the model.

Results

The distribution of PFC serum concentrations 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 frequencies: 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 1597

Table 1. LOD and precision data for the 12 polyfluoroalkyl compounds included in this study and a comparison of these parameters to the previously reported data for NHANES 1999-2000.

Precisiona

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.

aMean 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. bThe 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 calculate 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, education (p = 0.02), smoking status (p = 0.02),

and race/ethnicity-by-age (p < 0.01) and

Calafat et al.

1598 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. 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 1.0 (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 significantly between non-Hispanic whites and

non-Hispanic blacks (p = 0.49). PFOS and

PFNA LSGM concentrations were significantly 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 nonHispanic 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 MexicanAmerican males and non-Hispanic black

males and between non-Hispanic white males

and non-Hispanic black males were not statistically 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 18O2-PFOS, 13C2-PFOA, and 18O2-

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.

18O2-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 estimate 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 representative sample of the civilian, noninstitutionalized U.S. population, ≥ 12 years of age. These

findings confirm that measurable serum concentrations of these compounds were prevalent 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 producers have committed to reducing manufacturing 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 perfluorobutanesulfonyl fluoride, now used in the manufacture 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 workers 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, followed 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 contrast, 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 significantly 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 production 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 concentrations 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 concentration percentiles similarly decreased for

PFOS, PFOA, and PFHxS. We analyzed the

NHANES 1999–2000 and 2003–2004 samples by using two different methods; however,

these approaches provided equivalent results

[Table 1; Figures S1 and S2 in the Supplemental 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 concentrations 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 (temporal trends for PFOA were not examined) in

Arctic ringed seals in the same time (Butt et al.

2007). These decreases in serum concentrations 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 differences 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)

aFor 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 correlation between the serum concentrations of

PFOS and PFOA was higher than correlations of PFHxS and either PFOA or PFOS,

suggesting potential common exposure pathway(s) for PFOA and PFOS, but probably

not for PFHxS (mostly used in carpet-treatment 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 correlation 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 biodegradation of the volatile fluorotelomer alcohols

(Ellis et al. 2004). 

Current manufacturing practices exclusively 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 manufacturing 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 worldwide efforts continue in attempts to reduce

exposures to PFCs, including PFOS and

PFOA, and many halogenated POPs, including 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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