Polyfluoroalkyl Compounds in Pooled Sera from ... - ACS Publications

Feb 19, 2009 - The National Health and Nutrition Examination Survey (NHANES), conducted by the National Center for Health Statistics (NCHS) of the ...
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Environ. Sci. Technol. 2009, 43, 2641–2647

Polyfluoroalkyl Compounds in Pooled Sera from Children Participating in the National Health and Nutrition Examination Survey 2001-2002 KAYOKO KATO, ANTONIA M. CALAFAT,* LEE-YANG WONG, AMAL A. WANIGATUNGA, SAMUEL P. CAUDILL, AND LARRY L. NEEDHAM Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia

Received November 7, 2008. Revised manuscript received January 5, 2009. Accepted January 16, 2009.

To assess exposure of polyfluoroalkyl compounds (PFCs) among children, we measured the concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid, and 8 other PFCs in 24 pooled serum samples. The individual serum samples used to make the pools were collected from U.S. children who were participants in the 2001-2002 National Health and Nutrition Examination Survey. These children were from three major races/ ethnicities (non-Hispanic blacks, non-Hispanic whites, and Mexican Americans), two age categories (3-5 and 6-11 years), and both sexes. PFCs were extracted from 100 µL of serum using online solid-phase extraction coupled to isotope dilution high performance liquid chromatography tandem mass spectrometry; detection limits ranged from 0.1 to 0.4 ng/mL. In the final ANOVA models, race was the only significant demographic factor, and concentrations appeared to be lower for Mexican Americans than for the other two racial groups. For example, for Mexican American children 6-11 years old, the least-squares means (LSM) estimates were 30.45 ng/mL (PFOS) and 6.125 ng/mL (PFOA), while for non-Hispanic white children of the same age group, the LSM estimates were 42.45 ng/mL (PFOS) and 7.575 ng/mL (PFOA). However, after adjusting for the potential underestimation of variance associated with the sampling design, race did not remain a significant factor. Nevertheless, these findings suggest that human exposure to PFCs among the population groups of children examined may differ and stress the importance of identifying the environmental sources and routes of exposure to PFCs.

Introduction Polyfluoroalkyl compounds (PFCs) have been manufactured for over 50 years and are used in a variety of commercial applications such as water, oil, soil, and grease repellents for fabric, leather, rugs, carpets, stone, and tile, fire-fighting foams, alkaline cleaners, floor polish, sizing agents for packaging and paper products (to resist the spreading and penetration of liquids), and leveling agents for coatings (1, 2). * Corresponding author phone: (770) 488-7891; fax: (770) 4884371; e-mail: [email protected]. 10.1021/es803156p

Not subject to U.S. Copyright. Publ. 2009 Am. Chem. Soc.

Published on Web 02/19/2009

Two of the most widely studied PFCs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), can cross the placenta (3-5). Recent studies reported a small negative association between the concentrations of both PFOS and PFOA in cord serum and birth weight and size (6) between PFOA (but not PFOS) concentrations in maternal plasma and birth weight (5, 7) and between PFOS (but not PFOA) concentrations in maternal serum and birth weight (8). Nonetheless, some of the observed inconsistencies among these studies stress the need for additional research to assess the potential impact of exposures to PFOS and PFOA on fetal growth (9, 10). Some PFCs have demonstrated developmental, reproductive, and carcinogenic toxicity in animal studies (1, 11-13), although at serum concentrations orders of magnitude higher than those observed in the general population (14, 15). Recently, immunotoxicity in mice was reported at serum concentrations similar to those in the human general population (16). The developmental and reproductive potential toxicities of some PFCs are of concern from the perspective of children’s health. Potential sources of PFCs leading to human exposure include food (17-23), drinking water (24, 25), and dust (26-33), The fact that serum concentrations of some PFCs in children appear to be higher than in adults may be related to differences in sources and routes of exposure to PFCs between these two age groups (24, 25, 34-36). Assessing human exposure to PFCs among diverse age and race/ethnic groups may provide information useful for understanding the pathways of exposure to PFCs. The National Health and Nutrition Examination Survey (NHANES), conducted by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC), is an ongoing survey designed to evaluate the health and nutrition status of the civilian noninstitutionalized U.S. population (37). NHANES also includes exposure assessment of the U.S. general population to selected environmental chemicals, including PFCs (34, 35, 38). Unfortunately, PFCs exposure data in NHANES for children less than 12 years old are lacking because the volume of serum collected from preadolescents is limited. However, cotinine is measured in serum from all NHANES children 3-11 years old, and for some participants, sufficient serum remained after those analyses to prepare pooled samples. We report here the serum concentrations of 11 PFCs in 24 pooled serum samples, prepared from individuals 3-11 years old participating in NHANES 2001-2002, measured by using online solid-phase extraction (SPE) coupled to isotope dilution high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS).

Materials and Methods Preparation of the Pools. The sampling scheme for NHANES 2001-2002 was a complex multistage area probability design. Participation of the human subjects occurred only after obtaining informed consent (37). After collection, serum specimens were divided into aliquots, transferred to clean cryovials, frozen, shipped on dry ice to CDC’s National Center for Environmental Health, and stored at or below -20 °C. To prepare the pools, we used individual serum samples collected from the NHANES 2001-2002 participants aged 3-11 years old. This serum was residual serum from individual samples that had been previously analyzed for cotinine, a marker of environmental tobacco smoke (39). We consulted with NCHS staff and followed their recommendations for making the pools. We categorized the 1049 individual samples for which at least 500 µL of serum was available in VOL. 43, NO. 7, 2009 / ENVIRONMENTAL SCIENCE & TECHNOLOGY 9 2641

FIGURE 1. Mean and range of PFOS, PFOA, and PFNA by demographic group in pooled NHANES 2001-2002 sera from adolescents and adults (38) and from children. The rectangles represent the mean concentrations for males (M) and for females (F). The number of pools per demographic group is indicated in parentheses. Age groups (in years) are: 3-5, 6-11, 12-19, 20-39, 40-59, and 60+. 12 demographic groups, each representing a combination of race/ethnicity, sex, and age group (3-5 and 6-11 years) (Table S1 of Supporting Information). We used 936 randomly selected individual samples to prepare 24 pools (2 per demographic group) such as all pools included 21 (3-5 years of age) or 57 (6-11 years of age) individual samples (Table S1 of Supporting Information). The number of samples per pool was largely limited by having enough volume of pooled specimen for measuring not only PFCs but also various environmental chemicals of interest (e.g., polychlorinated p-dibenzodioxins, polybrominated diphenyl ethers, polychlorinated biphenyls [PCBs]) that require between 3 and 24 mL of serum for analysis. To ensure that no individual sample overly influenced the pooled results, all samples included in any one pool were of equal volume (i.e., 500 µL), except that 11 of the individual samples from non-Hispanic black females 3-5 years of age contributed less than 500 µL. After preparation, the serum pools were stored at or below -20 °C until analysis. Laboratory Measurements. By use of a modification of our analytical method (40), we measured the following 11 PFCs: perfluorooctane sulfonamide (PFOSA), 2-(N-ethylperfluorooctane sulfonamido) acetic acid (Et-PFOSA-AcOH), 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MePFOSA-AcOH), perfluorobutane sulfonic acid (PFBuS), perfluorohexane sulfonic acid (PFHxS), PFOS, perfluoroheptanoic acid (PFHpA), PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), and perfluorododecanoic acid (PFDoA). We used the following isotope-labeled internal standards for quantification: 18O2-PFOS (PFOS, PFBuS, and PFHxS), 13C2-PFOA (PFOA, PFHpA), 13C5-PFNA (PFNA), 13C2PFDeA (PFDeA and PFDoA), 18O2-PFOSA (PFOSA), D3-MePFOSA-AcOH (Me-PFOSA-AcOH), and D5-Et-PFOSA-AcOH (Et-PFOSA-AcOH). To compensate for the lack of isotopelabeled internal standards for PFBuS, PFHxS, PFHpA, and PFDoA and to account for potential matrix effects, we spiked the calibration standards into calf serum. Briefly, we added 250 µL of 0.1 M formic acid and 25 µL of internal standard solution to 100 µL of serum, and the spiked serum was vortexmixed and sonicated. The samples were placed on a Symbiosis online SPE system (Spark Holland, Plainsboro, NJ) for the preconcentration of the analytes on a Polaris C18 cartridge (7 µm, 10 × 1 mm, Spark Holland). The analytes 2642

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were transferred onto a Betasil C8 HPLC column (3 × 50 mm, 5 µm, ThermoHypersil Keystone, Bellefonte, PA), separated by HPLC (mobile phase A: 20 mM ammonium acetate in water, pH ) 4; mobile phase B: methanol), and detected by negative-ion TurboIonspray-MS/MS on an API 4000 mass spectrometer (Applied Biosystems, Foster City, CA). The limits of detection (LODs) were 0.1 ng/mL (PFOSA, PFBuS, PFHxS, PFOA, and PFNA), 0.2 ng/mL (PFOS, MePFOSA-AcOH, Et-PFOSA-AcOH, PFDeA, and PFDoA), and 0.4 ng/mL (PFHpA). Low-concentration quality control materials (QCs) and high-concentration QCs, prepared from a calf serum pool, were analyzed with the unknown samples and with reagent and serum blanks to ensure the accuracy and reliability of the data (40). Statistical Analysis. We performed the statistical analyses by using SAS software (SAS Institute, Cary, NC, version 9.1). For concentrations below the LOD, we used a value equal to the LOD divided by the square root of 2 (41). On the basis of self-reported data, a composite race/ethnicity variable helped define three major racial/ethnic groups: non-Hispanic blacks, non-Hispanic whites, and Mexican Americans. Because the concentrations of PFCs in individual samples from the U.S. general population are log-normally distributed (34, 35), the PFCs measured values for the pools are comparable to arithmetic averages of log-normal results (42) which should be approximately Gaussian. Thus we used analysis of variance (ANOVA) methods. Because the numbers of samples per pool were different for children aged 3-5 years (21 samples per pool) and for children aged 6-11 years (57 samples per pool), we used separate ANOVA models for each group. In the initial ANOVA models, we included sex, race, and the interaction between sex and race. In the ANOVA models, we assumed that the measured concentrations are independently and identically distributed. However, this distributional assumption is unlikely since the original sample data were obtained from a stratified multistage probability sample design. Therefore, to account for the potential underestimation of variance associated with our analyses, we also computed adjusted significance levels (Adj_ProbF) assuming design effects of 3.5 and 10 based on the recommendations of the NCHS staff. Then, we compared our “unadjusted” statistical results with those obtained using

TABLE 1. Concentrations (ng/mL) of PFCs in Pooled Serum Samples (Two Pools per Demographic Group) from Participants of NHANES 2001-2002 Ages 3-11 Years analyte

age (years)

sex

race

mean

pool 1

pool 2

analyte

age (years)

sex

race

mean

pool 1

pool 2

Et-PFOSA-AcOH Et-PFOSA-AcOH Et-PFOSA-AcOH Et-PFOSA-AcOH Et-PFOSA-AcOH Et-PFOSA-AcOH Et-PFOSA-AcOH Et-PFOSA-AcOH Et-PFOSA-AcOH Et-PFOSA-AcOH Et-PFOSA-AcOH Et-PFOSA-AcOH Me-PFOSA-AcOH Me-PFOSA-AcOH Me-PFOSA-AcOH Me-PFOSA-AcOH Me-PFOSA-AcOH Me-PFOSA-AcOH Me-PFOSA-AcOH Me-PFOSA-AcOH Me-PFOSA-AcOH Me-PFOSA-AcOH Me-PFOSA-AcOH Me-PFOSA-AcOH PFHxS PFHxS PFHxS PFHxS PFHxS PFHxS PFHxS PFHxS PFHxS PFHxS PFHxS PFHxS PFNA PFNA PFNA PFNA PFNA PFNA

3-5 3-5 3-5 3-5 3-5 3-5 6-11 6-11 6-11 6-11 6-11 6-11 3-5 3-5 3-5 3-5 3-5 3-5 6-11 6-11 6-11 6-11 6-11 6-11 3-5 3-5 3-5 3-5 3-5 3-5 6-11 6-11 6-11 6-11 6-11 6-11 3-5 3-5 3-5 3-5 3-5 3-5

F F F M M M F F F M M M F F F M M M F F F M M M F F F M M M F F F M M M F F F M M M

NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW

1.2 1.2 1.45 1.3 1.05 0.95 0.8 0.9 1 0.9 0.9 0.7 5.15 4.2 4.9 5.3 2.45 5.55 2.65 2.65 3.35 3.45 2.8 2.85 9.7 4.15 18.7 12.45 12.05 13.1 13.6 8 12 10.9 7.95 13.15 1.15 0.7 1.05 1.2 0.65 0.75

0.8 1.2 1.0 1.5 1.3 0.9 0.7 0.9 0.8 0.7 0.9 0.6 5.2 3.1 3.6 4.6 3.5 3.9 2.7 2.7 2.7 3.6 2.9 2.9 9.8 3.5 18.6 8.9 10.9 17.2 16.2 7.9 7.6 9.6 8.0 15.2 1.0 0.7 0.8 1.3 0.7 0.8

1.6 1.2 1.9 1.1 0.8 1.0 0.9 0.9 1.2 1.1 0.9 0.8 5.1 5.3 6.2 6.0 1.4 7.2 2.6 2.6 4.0 3.3 2.7 2.8 9.6 4.8 18.8 16.0 13.2 9.0 11.0 8.1 16.4 12.2 7.9 11.1 1. 3 0.7 1.3 1.1 0.6 0.7

PFNA PFNA PFNA PFNA PFNA PFNA PFOA PFOA PFOA PFOA PFOA PFOA PFOA PFOA PFOA PFOA PFOA PFOA PFOS PFOS PFOS PFOS PFOS PFOS PFOS PFOS PFOS PFOS PFOS PFOS PFOSA PFOSA PFOSA PFOSA PFOSA PFOSA PFOSA PFOSA PFOSA PFOSA PFOSA PFOSA

6-11 6-11 6-11 6-11 6-11 6-11 3-5 3-5 3-5 3-5 3-5 3-5 6-11 6-11 6-11 6-11 6-11 6-11 3-5 3-5 3-5 3-5 3-5 3-5 6-11 6-11 6-11 6-11 6-11 6-11 3-5 3-5 3-5 3-5 3-5 3-5 6-11 6-11 6-11 6-11 6-11 6-11

F F F M M M F F F M M M F F F M M M F F F M M M F F F M M M F F F M M M F F F M M M

NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW NHB MA NHW

1.1 0.6 0.95 1.2 0.65 0.85 7.45 6.85 7.4 7.4 6.15 7.75 6.8 5.95 7.55 8 6.3 7.6 36 29.9 41.9 40.85 31.1 39.1 36.5 31.7 44.35 41.85 29.2 40.55 0.5 0.45 0.4 0.45 0.35 0.6 0.45 0.5 0.8 0.6 0.55 0.7

0.9 0.6 0.9 1.0 0.7 0.8 6.5 5.9 6.5 8.0 6.5 7.3 6.8 6.0 7.2 7.8 5.9 8.0 32.7 29.6 33.2 37.0 32.6 41.0 33.7 31.9 36.3 37.1 27.5 43.1 0.4 0.3 0.3 0.5 0.4 0.3 0.4 0.4 0.6 0.5 0.5 0.7

1.3 0.6 1.0 1.4 0.6 0.9 8.4 7.8 8.3 6.8 5.8 8.2 6.8 5.9 7.9 8.2 6.7 7.2 39.3 30.2 50.6 44.7 29.6 37.2 39.3 31.5 52.4 46.6 30.9 38.0 0.6 0.6 0.5 0.4 0.3 0.9 0.5 0.6 1.6 0.7 0.6 0.7

TABLE 2. ANOVA Significance Levels for Race after Adjustment of the Mean Square Error to Account for an Assumed Design Effecta analyte (age in years)

ProbF

Adj ProbF (deff ) 3.5)

Adj ProbF (deff ) 10)

PFNA (3-5) PFNA (6-11) PFOA (6-11) PFOS (6-11)

0.0114 0.0025 0.0074 0.0294

0.17 0.07 0.13 0.27

0.49 0.33 0.44 0.6

a ProbF is the observed significance level (p value) from ANOVA assuming the measured pool values are independently identically distributed, which is unlikely since the original sample data were obtained from a stratified multistage probability design. Therefore, adjusted significance levels (Adj_ProbF) were also computed assuming a design effect (deff) equal to 3.5 or 10, chosen as a conservative estimate of how large the design effect might be based on NCHS’ recommendations.

these two conservative estimates of how large the design effect might be. We considered analyses to be statistically significant when p e 0.05.

Results and Discussion Eight of the PFCs (PFOS, PFOA, PFHxS, PFNA, Et-PFOSAAcOH, Me-PFOSA-AcOH, PFOSA, and PFHpA) were detected in all of the pools analyzed. These data suggest that, as for adults (38), exposure to several PFCs among young children

was also prevalent in the United States in the early 2000s. By contrast, PFBuS and PFDoA were not detected in any of the pools, and PFDeA was detected in only 5 of them. These findings suggest that in 2001-2002 human exposures to these PFCs were not as prevalent as for the other PFCs or that pharmacokinetic factors are different. PFBuS, PFDoA, PFDeA, and PFHpA (detected frequently, but at concentrations close to the LOD) will not be discussed further. Similar to previous findings in populations nonoccupationally exposed to PFCs (35, 36, 43, 44), the mean concentrations of PFOS in these pooled samples were greater than the mean concentrations of the other PFCs. The mean and each individual pool concentration of PFOS, PFOA, PFHxS, PFNA, PFOSA, Me-PFOSA-AcOH, and Et-PFOSA-AcOH for the 12 possible combinations of race/ethnicity, sex, and age groups are shown in Table 1. PFOS, PFOA and PFHxS concentrations are given in Figure S1 of Supporting Information. Previously, we reported the concentrations of PFCs in pooled sera collected from g12-year-old participants of the 2001-2002 NHANES (38). Figures 1-3 show the mean and ranges of concentrations for PFOS, PFOA, PFHxS, PFNA, PFOSA, Me-PFOSA-AcOH, and Et-PFOSA-AcOH for the 24 possible combinations of race/ethnicity, sex, and age groups for the NHANES 2001-2002 serum pools of children and adolescents/adults. In general, the mean concentrations of PFOS, PFOA, PFNA, PFHxS, Me-PFOSA-AcOH, and Et-PFOSA-AcOH in the children’s pools were similar regardless of age (3-5 vs 6-11 years old) or sex and were higher than the mean concentraVOL. 43, NO. 7, 2009 / ENVIRONMENTAL SCIENCE & TECHNOLOGY

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FIGURE 2. Mean and range of Et-PFOSA-AcOH and PFOSA by demographic group in pooled NHANES 2001-2002 sera from adolescents and adults (38) and from children. The rectangles represent the mean concentrations for males (M) and for females (F). The number of pools per demographic group is indicated in parentheses. Age groups (in years) are: 3-5, 6-11, 12-19, 20-39, 40-59, and 60+.

FIGURE 3. Mean and range of PFCs associated with carpet treatment products by demographic group in pooled NHANES 2001-2002 sera from adolescents and adults (38) and from children. The rectangles represent the mean concentrations for males (M) and for females (F). The number of pools per demographic group is indicated in parentheses. Age groups (in years) are: 3-5, 6-11, 12-19, 20-39, 40-59, and 60+. tions for adolescents and adults (Figures 1-3). However, these comparisons must be interpreted with caution because pooled sample PFC concentrations cannot be compared across demographic groups or across studies if the amongsubject variances of the compounds of interest tend to vary with increasing concentration. Nonetheless, others previously reported higher serum mean concentrations of selected PFCs, specifically PFHxS and Me-PFOSA-AcOH, from U.S. children than from adults (36). Me-PFOSA-AcOH is a known oxidation product of 2-(N-methyl-perfluorooctane sulfonamido) ethanol, which has been used primarily in surface treatment applications for carpets and textiles (43). PFHxS was used as a building block for compounds incorporated in fire-fighting foams and specific postmarket carpet treatment applications (43). One explanation for the apparent greater mean concentrations of PFHxS and Me-PFOSA-AcOH in children than in 2644

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adolescents and adults (Figure 3) is increased exposure among children resulting from increased contact with carpeted floors and upholstered furniture coupled with handto-mouth activity. Carpets and upholstered furniture are known to trap dust, which may contain PFHxS. In fact, the mean concentrations of PFHxS in archived house dust samples collected in the United States in 2000-2001 were higher than for other PFCs (32); indoor dust concentration data on Me-PFOSA-AcOH are not available. In the final ANOVA models for the statistical analysis of the children’s pools, race was the only significant demographic factor for serum concentrations of PFNA for children aged 3-5 years and for serum concentrations of PFOS, PFOA, and PFNA for children aged 6-11 years (Table 2). However, after we adjusted the F value by the two different design effects of 3.5 and 10, race did not remain a significant factor (Table 2). The estimated least-squares means (LSMs) and

TABLE 3. LSMa Estimates and Their 95% Confidence Limits (ng/mL) age (years) analyteb racec 6-11 6-11 6-11 6-11 6-11 6-11 6-11 6-11 6-11 3-5 3-5 3-5

PFOS PFOS PFOS PFOA PFOA PFOA PFNA PFNA PFNA PFNA PFNA PFNA

means

L95

U95

NHB 39.175 33.11 45.24 MA 30.45 24.39 36.51 NHW 42.45 36.39 48.51 NHB 7.4 6.80 8.00 MA 6.125 5.52 6.73 NHW 7.575 6.97 8.18 NHB 1.15 0.98 1.32 MA 0.625 0.46 0.79 NHW 0.9 0.73 1.07 NHB 1.175 0.97 1.38 MA 0.675 0.47 0.88 NHW 0.9 0.70 1.10

Adj L95d (deff ) 3.5) Adj U95d (deff ) 3.5) Adj L95d (deff ) 10) Adj U95d (deff ) 10) 29.35 20.62 32.62 6.43 5.15 6.60 0.88 0.35 0.63 0.84 0.34 0.57

49.00 40.28 52.28 8.37 7.10 8.55 1.42 0.90 1.17 1.51 1.01 1.23

22.56 13.84 25.84 5.76 4.48 5.93 0.69 0.17 0.44 0.61 0.11 0.34

55.79 47.06 59.06 9.04 7.77 9.22 1.61 1.08 1.36 1.74 1.24 1.46

a

LSM and arithmetic means are equivalent when only one factor is included in the model. b PFOS, perfluorooctane sulfonic acid; PFOA, perfluorooctanoic acid; PFNA, perfluorononanoic acid; MA, Mexican Americans; NHB, non-Hispanic blacks; NHW, non-Hispanic whites. c L95 and U95 are the lower and upper 95% confidence limits, respectively, assuming the measured pool values are independently identically distributed. d Adj L95 and Adj U95 are the 95% confidence limits, respectively, that result when assuming a design effect (deff) of 3.5 or 10.

associated 95% confidence intervals of PFC concentrations for these demographic groups before and after adjusting for design effect are given in Table 3. Several factors must be taken into consideration when interpreting these results. First, because the individual samples used to prepare the pools originated from NHANES 2001-2002, which was designed to be representative of the noninstitutionalized U.S. population, the pools should provide good coverage of the U.S. population. However, by pooling across design cells, we cannot be assured that estimates based on the pooled samples are unbiased. Second, the ANOVA LSMs represent positively biased estimates of the central values of the 12 demographic groups (6 for children aged 3-5 years and 6 for children aged 6-11 years). This additional positive bias, which we made no attempt to correct, arises from the inherent bias associated with the measured concentrations of the pools (42). Data on the serum concentrations of PFCs in U.S. children are limited to one study of 598 children 2-12 years of age (36) and one study in which children had been exposed to PFOA through drinking water accidentally contaminated with PFOA (24). As expected, the PFOA mean concentrations in the current study were considerably lower than the mean concentrations reported among children 2-5 and 6-10 years of age who consumed drinking water contaminated with PFOA (24). By contrast, the mean concentrations of PFOA and PFOS from the present study were similar to the concentrations reported for the 598 children, who provided their serum samples in 1994-95 (36), while the mean levels for PFHxS and Me-PFOSA-AcOH were slightly higher. Although the comparison of the individual PFCs concentrations (36) and our pooled data has limitations (e.g., pooled sample measurements of log-distributed data are likely to be positively biased), these results suggest that exposure to PFCs among children was prevalent for at least the time period encompassed by these two studies, although the exposure levels may have changed from the mid 1990s to the early 2000s. In summary, the degree of exposure and the dominant exposure pathways to PFCs may depend on the exposure scenario and on the particular age and associated lifestyle and activities of the subjects. Diet is a potential source of exposure to PFOS and PFOA (17-20), but for some PFCs, unlike the traditional lipid soluble persistent chlorinated organic chemicals (e.g., PCBs), dietary ingestion may not be the primary exposure route. For example, house dust and indoor air (26, 28, 30-33) and drinking water (24, 25) may be important sources of exposure to some PFCs. Also, for the PFCs, the relative concentrations in breast milk compared to the respective serum concentrations are much less than

for traditional persistent organic chemicals (45-47), However, as with PCBs and other halogenated persistent organic pollutants, transplacental transfer of PFCs has been reported (3, 4, 6, 48). Our results are based on the analyses of a limited number of serum pools. Additional studies should include individual samples from these age ranges and even younger children. Also, the high prevalence of exposure to some PFCs among young children highlights the need for continuing efforts to identify sources of human exposure to PFCs, especially among children, and to study the environmental distribution of these chemicals.

Acknowledgments We thank Jack Reidy and Xavier Bryant for technical assistance. We also acknowledge Lester R. Curtin, Susan E. Schober, and Geraldine M. McQuillan (NCHS/CDC) for their input in the design of the pools and statistical analysis of the data. This research was supported in part by an appointment (Amal Wanigatunga) to the Research Participation Program at the Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and CDC.

Supporting Information Available Number of individual NHANES 2001-2002 serum samples available and used for making the pools and mean and range of PFOS, PFOA and PFHxS by demographic group in the NHANES 2001-2002 children’s pool samples. This information is available free of charge via the Internet at http:// pubs.acs.org.

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