Temporal Changes in the Levels of Perfluorinated Compounds in California Women's Serum over the Past...

Published: July 06, 2011

r 2011 American Chemical Society 7510 dx.doi.org/10.1021/es2012275 | Environ. Sci. Technol. 2011, 45, 7510–7516

ARTICLE

pubs.acs.org/est

Temporal Changes in the Levels of Perfluorinated Compounds inCalifornia Women’s Serum over the Past 50 YearsMiaomiao Wang,* June-Soo Park, and Myrto Petreas

Department of Toxic Substances Control, California Environmental Protection Agency, Berkeley, California 94710, United States

bS Supporting Information

’ INTRODUCTION

Perfluorinated compounds (PFCs) are of particular interest asemerging environmental contaminants. They are found in theenvironment and in biota due to the manufacturing of PFCs,their industrial application practices and their widespread use inconsumer products.1�3 They have been widely used as protectivecoatings in a variety of industrial applications, such as in textilesand paper and as surfactants for more than 50 years. Thedetection of certain PFCs, particularly perfluorooctane sulfonate(PFOS) and perfluorooctanoic acid (PFOA) in water systems,house dust, and wildlife,4�13 has raised concerns about theirpersistence and bioaccumulation in the environment. Among thevarious PFCs, PFOS and PFOA are found in the highestconcentration ranges in the environment and have been foundin human serum around the world.14�28 Both PFOS and PFOAhave demonstrated toxicity in lab animals (adverse effects onreproductive and developmental systems, fatty acid metabolismand liver damage) as well as adverse effects on human health.29�31

Recent studies have shown the presence of certain PFCs in breastmilk,32�34 and their placental transport.32,35 Due to its persis-tence and bioaccumulative properties, PFOS has been added tothe 2009 Stockholm Convention list of POPs (persistent organicpollutants).

PFCs may enter the environment from several sources such asthe manufacturing of perfluoralkylsulfonyl-based substances byelectrochemical fluorination (ECF),36 telomerization of penta-fluoroiodoethane with tetrafluoroethylene oligomers,1 the environ-mental degradation of perfluorooctanesulfonyl fluoride (POSF)

and related products,37�39 and from various industrial applica-tions, such as water- and oil-repellant coatings.40,41 AlthoughPFCs (particularly PFOS, PFOA, and perfluorohexane sulfonateor PFHxS) have been widely detected in environmental samples,there are only a few studies on time trends in humans andother biota,12,15,28,33,42�45 and fewer still in human milk orserum.15,28,42,43 Temporal trend studies are valuable tools forevaluating the contaminants’ status, their persistence, changes insources of exposure and the efficacy of environmental regula-tions. Data from the National Health and Nutrition ExaminationSurvey (NHANES) from 1999 to 2000 and 2003�2004 showeda decrease in PFOS concentrations in the U.S. population,consistent with the phase out by 3M of manufacturing processesbased on POSF chemistry, and with more strict regulationsoverall. However, to our knowledge, there is no report on PFClevels in human serum samples as early as the 1960s, neither onhuman population time trend studies from the 1960s to thepresent. Such data would expand the present knowledge onPFCs and would provide valuable information on the earlycontamination profiles of PFCs, since the manufacturing practicebased on POSF chemistry started as early as 1949.1 Here wereport on how we adapted and validated an online SPE-HPLC-MS/MS method based on the Center for Disease Control

Received: April 11, 2011Accepted: July 6, 2011Revised: June 29, 2011

ABSTRACT: Serum samples collected from California women atdifferent time periods: 1960s (n = 40), 1980s (n = 30), and 2009 (n =35) were examined for the presence of 12 perfluorinated compounds(PFCs) using an online SPE-HPLC-MS/MS method. At each timeperiod, perfluorooctane sulfonate (PFOS) was present at the highestconcentration, followed by perfluorooctanoic acid (PFOA, except inthe 1960s). We found the highest levels of PFOS (median = 42.1 ng/mL) and perfluorohexane sulfonate (PFHxS, median = 1.56 ng/mL)in the 1960s samples, possibly reflecting widespread use of precursorPFCs. PFOS showed a statistically significant drop from the 1960s tothe 1980s (28.8 ng/mL ) and to 2009 (9.0 ng/mL ), the latter being inagreement with national data. For PFOA, there was an approximately10-fold increase in median concentrations from the 1960s (0.27 ng/mL) to the1980s (2.71 ng/mL), and a slight drop in the 2009 samples (2.08 ng/mL). For longer chain perfluorocarboxylic acids(PFCAs), there was a continuous build-up in serum from the 1960s to 2009. To our knowledge, this is the first study to investigatetemporal changes of PFCs over the past 50 years.

7511 dx.doi.org/10.1021/es2012275 |Environ. Sci. Technol. 2011, 45, 7510–7516

Environmental Science & Technology ARTICLE

(CDC) protocol,27,46 and examined the concentrations of PFCsin serum samples from California women collected from the1960s, the 1980s, and 2009. The data trends are compared withU.S. data and data from other geographic locations.

’MATERIALS AND METHODS

Sample Populations. Samples were collected from threedifferent time periods.The 1960s samples (n = 40, drawn between 1960 and 1963)

were randomly selected among over 500 archived samples ofpregnant women participating in a study of reproductive out-comes nested within the historic Child Health and DevelopmentStudies (CHDS) cohort. The CHDS47 is a longitudinal study ofover 20 000 pregnancies among Northern California KaiserFoundation Health Plan members, with subjects enrolled be-tween 1959 and 1966.The 1980s samples (n = 30, drawn between 1981 and 1986)

were randomly selected among archived serum samples fromcancer-free women (controls) participating in a breast cancerstudy.48

The 2009 samples (n = 35) were from a pilot study for theCalifornia Environmental Contaminants Biomonitoring Program.49

All serum samples were from California women49 and wereobtained with informed consent processes. All samples werestored at �80 �C or �20 �C prior to analysis.Standards and Materials. The following labeled compounds

and native PFC standards were purchased from Wellington Labo-ratories (Guelph, Ontario, Canada): PFOS (perfluorooctanesulfonate), PFHxS (perfluorohexane sulfonate), PFBS (perfluoro-butane sulfonate), PFOA(perfluorooctanoic acid), PFNA (per-fluoronanonoic acid), PFHpA (perfluoroheptanoic acid), PFDA(perfluorodecanoic acid), PFUA (perfluoroundecanoic acid),

PFDoA (perfluorododecanoic acid), PFOSA (perfluooctane sulfo-namide), Et-PFOSA-AcOH(2-(N-ethyl-perfluorooctane sulfoamido)acetic acid), and Me-PFOSA-AcOH (2-(N-methyl-perfluorooc-tane sulfoamido) acetic acid). Reagents (including methanol andwater (both HPLC grade), glacial acetic acid, ammonia, formicacid) were purchased from Mallinckrodt Baker (formerly J.T.Baker, Phillipsburg, NJ)Sample Preparation and Analysis. Our method is based on

an online SPE-HPLC-MS/MS method,46 with details describedin the Supporting Information (SI). Briefly, 100 μL of serumwere mixed with 0.1 M formic acid, and internal standards wereadded (13C2-PFOA and 13C4-PFOS), then injected by an onlineSPE-HPLC system (Symbiosis Pharma system with Mistral CSCool, SparkHolland Inc.) to aC18 cartridge (HySphereC18HD, 7μm, 10 � 2 mm). After washing, the target analytes were elutedto a C8 HPLC column (BETASIL C8 column, Thermo FisherScientific) for separation. The eluate was then introduced to theMS/MS (ABSciex 4000 QTrap) for multiple-reaction-monitoring(MRM) analysis. The area of the Q1/Q3 ion pairs was used inthe analysis. Regression coefficients of 0.98 to 0.99 were generallyobtained.Quality Control. The method was validated by repeatedly

analyzing blank calf serum spiked with unlabeled PFC standardsat two different levels (low and high). Furthermore, standardreference materials (SRM 1958) from the National Institute ofStandards and Technology, as well as PFC-spiked samples ofknown concentration from the CDC were used as referencematerials.50 A summary chart of interlaboratory comparisonstudies is shown in the SI (Figure S1 A and B).Blank samples (bovine serum) were also processed with each

batch of samples, and no PFCs were detected above therespective LODs (defined as 3 times the standard deviation ofthe blank and listed in Table 1).

Table 1. Summary of PFCs Concentration (ng/mL) Detected in the Serum Samples, Detection Frequency, And Limit ofDetection (LOD) for Each Analytea

aNA, not applicable. SE, standard error. DF, detection frequency. NR, not reported.



Statistical Analysis. As the data were not normally distrib-uted, we used the nonparametric test for trend across orderedgroups developed by Cuzick51 and the Kruskal�Wallis equality ofpopulations rank test (STATA, Statistical data analysis software,11th edition. StataCorp., College Station, TX) to compare theconcentrations of each chemical across the three time periods.The Spearman rank correlation coefficient was used to assess therelationship between individual PFCs in the samples.

’RESULTS AND DISCUSSION

Individual PFC levels in serum from the 1960s, 1980s and2009 are shown in the SI, Tables S1 A, B, and C, respectively.Summary statistics are shown in Table 1. PFOS and PFHxS weredetected in all the serum samples, whereas PFOA, PFDA, Et-PFOSA-AcOH, and PFOSA were detected in the majority of thesamples. Neither PFBS nor PFDoA were measured above thedetection limit in any of the serum samples.Perfluorosulfonates. PFOS showed decreasing trends from

the 1960s to 2009 (Figure 1 A and B) that were statisticallysignificant (p < 0.001). Given our sampling times, in the currentstudy we have no data on whether concentrations might haveincreased between the 1980s to early 2000 as others havereported.28 The decreasing trends of PFOS and PFHxS fromthe 1980s to 2009, in general, are consistent with the phase out ofthe perfluorooctyl manufacturing practice in 2002.43 They alsoagree well with the NHANES data, as shown in Figure 1.However, the levels of PFOS and PFHxS in the 1960s serum

samples were unexpectedly high. To our knowledge, there are noreports on human serum samples as early as the 1960s: whilethere is one report on organic fluorine in human blood from the1960s (∼1 μM organic fluorine in serum), due to technicalrestrictions at that time, it is not clear which specific compoundwas the major component.52

Based on our QC and interlaboratory studies (SI Figure S1),we believe that the presence of PFOS and PFHxS in the 1960ssamples was not an artifact introduced either through labora-tory background or detection error, nor was it likely asystematic contamination attributable to materials used forsample collection and storage. Our belief is, in part, based onthe wide range of PFOS concentrations detected (8.3�124ng/mL). To our knowledge, the samples were collected andstored using the same protocol and, therefore, the wide rangeof PFOS concentrations within this batch can only be attrib-uted to the wide differences among individual samples. PFOSresults reported from global populations in the 1970s were notconsistent. In one study, only 3.8 ng/mL of PFOS weredetected in pooled serum samples that were collected in1977 in Norway.42 In another study, a median value of 29.5ng/mL PFOS was detected in archived serum samples thatwere collected from Maryland, U.S. in 1974 (n = 178).28 Thisis the earliest report on U.S. serum and it is, therefore, likelythat PFOS was present in high concentrations in human serumas early as the 1960s in the U.S. When we examined the 1960sconcentrations by the year of sample collection we foundstatistically significant increasing trends from 1960 to 1963 forPFOS (p < 0.001) and PFHxS (p < 0.001). This may reflectincreasing use of Scotchgard-containing products in theearly 1960s.Furthermore, there are interesting, and statistically significant,

correlations observed between PFOS and PFHxS. PFHxS, also akey ingredient in the Scotchgard line, showed similarly highconcentrations in our 1960s serum samples (Figure 1B). Thedetection of both octa- and hexa- forms of perfluorosulfonatesstrongly confirms the presence of these compounds as early asthe 1960s. The strongest correlations were observed for samplescollected in the 1960s (r = 0.92, Table 2a), again confirming thepresence of high PFOS in serum as early as 1960s. There was asimilar correlation in the 1980s samples (r = 0.83, Table 2b), butnot in the 2009 samples (r = 0.27, Table 2c). These correlationsindicate that both PFOS and PFHxS have significant overlap insources that contribute to their environmental presence. Thereduced correlation in 2009 might be due to their different half-lives (5.4 years for PFOS, and 8.5 years for PFHxS),53 and thusdifferent persistence in biota, or might be indicative of new anddifferent sources that contribute to contemporary levels of PFOSand PFHxS.Perfluorooctanesulfonamide. PFOSA, Me-PFOSA acetic

acid, and Et-PFOSA acetic acid showed trends similar to oneanother: an increase until the 1980s and a decrease since then.PFOSA is also the product of the ECF chemistry and a degrada-tion precursor of PFOS. However, the strongest correlation wasfound between PFOS and PFOSA in serum samples from the1960s (r = 0.69, Table 2a), and deceased in 1980s (r = 0.21,Table 2b), and 2009 (r = 0.41, Table 2c), indicating that morerecently, there are multiple sources of PFOS in the environmentother than PFOSA degradation. There is a quite strong correla-tion between PFOSA and Et-PFOSA in the 2009 serum samples(r = 0.59, Table 2c), suggesting that Et-PFOSA is a precursor andsignificant source of environmental PFOSA. The time trend of

Figure 1. A and B. Concentrations (mean and standard error) in ng/mL of PFOS and PFHxS in serum samples from the three time periods.NHANES data for female serum (Geometric mean value (GM)) areplotted as references.



PFOSA (Figure 2) clearly indicates the build up of PFOSA inserum from the 1960s to the 1980s, and its decrease by 2009.This decrease of PFOSA down to around the limit of detectionlevels in the 2009 samples indicates that exposure to PFOSA hasbeen effectively decreased by the regulation of ECF chemistry, byPFOSA’s degradation in the environment and the eliminationfrom the human body. Interestingly, a study of 84 pooled serum

samples (from 2420 individuals) in Australia collected in2006�2007 has shown similar levels for PFOSAs16 comparedto our 2009 serum samples: while Me-PFOSA was still detectedin 94% of the samples, there was a detection frequency of only24% in all the samples for PFOSA, and Et-PFOSA was detectedin only 1% of the samples, again reflecting a clear impact of thephase out of the POSF chemistry.Perfluorocarboxylic Acid. PFOA showed an increase of

approximately 10-fold from the 1960s to the 1980s, followedby a slight decrease. However, as we had no samples collected inthe early 2000s, we may have missed the peaking period ofPFOA’s presence. Furthermore, compared to PFOS and PFOSA,PFOA does not show such a big decrease from the 1980s to 2009,as shown in Figure 3. PFOS has a three- fold decrease (about31%), while PFOA has only decreased to about 77% of theoriginal value from the 1980s to 2009. This might indicatealternate sources of PFOA in the environment other than theECF manufacturing that was phased out during this time period.For example, fluorotelomer alcohol degradation can contributeto PFCAs of various chain lengths.37,38 Furthermore, the levels ofPFNA, PFDA and PFUA in our study showed increases from the1960s to 2009 (Figure 4 and SI Figure S3), although PFDA andPFUA were either not present or below the detection limit in theNHANES data. These differences might indicate differences inexposures between California and the U.S. in general, although ourlimited sample size and the lack of statistical representativeness

Table 2. Spearman Rank Correlation Coefficients between Concentrations of PFCs in Serum Samples from Each of the ThreeTime Periodsa

aNA: not applicable.

Figure 2. Concentrations (mean and standard error) in ng/mL ofPFOSA in serum samples from the 3 time periods. NHANES data forfemale serum (GM) from 1999 to 2000 and from 2003 to 2004 areplotted as references.



should be taken into account. As shown in Figure 4B, PFDA hasan approximately 6-fold increase from the 1960s to 2009(medians from 0.06 to 0.37 ng/mL in serum), while PFUAwas below the detection limit in the 1960s, but was detected witha median of 0.17 ng/mL in our 2009 serum (SI Figure S3). Thesetrends were statistically significant for both PFDA and PFUA.

These longer chain PFCAs have also been detected globallyrecently: PFDA was detected in 2006�2007 Australian serumsamples (0.3 ng/mL),16 PFDA and PFUA in contemporaryChinese serum samples (0.38 and 0.76 ng/mL, respectively),19

and in Swedish serum samples collected between 1996 and 2004(0.53 and 0.40 ng/mL, respectively).26 Globally, it appears thatthe longer chain PFCAs have been building-up in human serum.Possible reasons for such a build-up include the persistence of thesources and the longer half-lives of these compounds comparedto PFOA.54,55 It would be interesting to keep monitoring thesecompounds in biota samples.Correlation Trends between PFCs. Statistically significant

correlations existed not only for the closely related PFOS�PFHxSpair, but also for other related PFCs, including PFOS and PFOA,PFOS and PFOSA, PFOSA and Et-PFOSA, and PFHxS andPFOA (Table 2a�c). Moreover, there was a decreasing trend inthe correlation between these compounds from the 1960s to2009. As mentioned above, the longer exposure time, multipleexposure sources and different half-lives for these compoundscontribute to the decreasing trend in correlation.Interestingly, however, there was an increasing trend in the

correlation between long chain PFCA compounds. Most of thesecompounds were not detected in the 1960s, and, therefore, onlydata from the 1980s and 2009 were available for comparison.Correlation coefficients for PFNA and PFDA increased from0.28 to 0.74; for PFNA and PFOA from 0.30 to 0.72; and forPFDA and PFUA from �0.21 to 0.68 (Table 2b and 2c). Onereason for the change might be the changes of PFCA sources: themanufacturing of ammonium perfluorooctanoate (APFO) bythe ECF process ceased by 2002 in the U.S.2 whereas thefluoropolymer manufacturing process of APFO and APFN(ammonium perfluorononanoate) became the major source ofPFCAs. It would be interesting to observe whether or not thetrend continues in the future.A limitation of our study is the fact that it was based on a

convenience sample of three discrete populations of Californiawomen that was not selected in any statistically based way. The1960s group was comprised of pregnant women who wereyounger than the other two groups. Metabolic changes andblood volume expansion during pregnancy are known to alterbody burdens of many chemical contaminants. In particular,albumin levels are lower during pregnancy56 and PFCs bind toit.57 Interestingly, in a study using NHANES data, pregnantwomen had lower PFOS levels than nonpregnant women.56

Therefore, the 1960s PFOS levels could have been even higher ifnonpregnant women had been sampled, further supporting thedownward trend we observed.Our study is the first to report time trends of PFCs in

California women over the last 50 years. The changes in theconcentrations of the PFCs in serum samples from the 1960s to2009 indicate increasing exposure during the time of wide usageof these chemicals and then decreasing exposure once thecontaminant sources were reduced or removed. While contem-porary levels seem to be in agreement with NHANES, we foundunexpectedly high levels of PFOS and PFHxS in the 1960ssamples. We are currently exploring these chemicals as riskfactors in our original epidemiologic study of thyroid effects.The relative profiles of PFCs have changed over time, probablyreflecting patterns of use and contemporary patterns are similarto NHANES. In addition, we found increasing trends in levels oflonger chain PFCAs which were present in the majority of thecontemporary serum samples.

Figure 4. A and B. Concentrations (mean and standard error) in ng/mL of PFNA and PFDA in serum samples from the three time periods.For values lower than LOD, half of the LOD value was used in the plots.NHANES data for female serum (GM) (for PFNA only) are plotted asreferences. PFDA was either not detected or lower than LOD in the1999 and 2003 NHANES data.

Figure 3. Concentrations (mean and standard error) in ng/mL ofPFOA in serum samples from the three time periods. NHANES data forfemale serum (GM) are plotted as references.



’ASSOCIATED CONTENT

bS Supporting Information. Descriptions of methods andPFC concentrations for individual samples. This material isavailable free of charge via the Internet at http://pubs.acs.org.

’AUTHOR INFORMATION

Corresponding Author*Phone: (510) 540-2925; fax: (510) 540-2305; e-mail: [email protected].

’ACKNOWLEDGMENT

We thank W. Guo, F.R. Brown, S. Harwani (ECL, DTSC); A.Calafat, M. Davis (CDC); K. Kannan (NYDPH); C. Huset (MNDPH) for their support and help in sharing samples, interlabora-tory reference materials, and discussion. We thank Drs. Mary A.Kaiser and Barbara S. Larsen of DuPont Corporate Center forAnalytical Sciences for reviewing an early draft and providing uswith insightful comments. The ideas and opinions expressedherein are those of the authors and do not necessarily reflect theofficial position of the California Department of Toxic Sub-stances Control.

’REFERENCES

(1) Houde, M.; Martin, J. W.; Letcher, R. J.; Solomon, K. R.; Muir,D. C. G. Biological monitoring of polyfluoroalkyl substances: A review.Environ. Sci. Technol. 2006, 40 (11), 3463–3473.(2) Prevedouros, K.; Cousins, I. T.; Buck, R. C.; Korzeniowski, S. H.

Sources, fate and transport of perfluorocarboxylates. Environ. Sci.Technol. 2006, 40 (1), 32–44.(3) Giesy, J. P.; Kannan, K. Global distribution of perfluorooctane

sulfonate in wildlife. Environ. Sci. Technol. 2001, 35 (7), 1339–1342.(4) Kato, K.; Calafat, A. M.; Needham, L. L. Polyfluoroalkyl chemi-

cals in house dust. Environ. Res. 2009, 109 (5), 518–523.(5) Jin, Y. H.; Liu, W.; Sato, I.; Nakayama, S. F.; Sasaki, K.; Saito, N.;

Tsuda, S. PFOS and PFOA in environmental and tap water in China.Chemosphere 2009, 77 (5), 605–611.(6) Martin, J. W.; Smithwick, M. M.; Braune, B. M.; Hoekstra, P. F.;

Muir, D. C. G.; Mabury, S. A. Identification of long-chain perfluorinatedacids in biota from the Canadian Arctic. Environ. Sci. Technol. 2003, 38(2), 373–380.(7) Martin, J. W.; Whittle, D. M.; Muir, D. C. G.; Mabury, S. A.

Perfluoroalkyl contaminants in a food web from Lake Ontario. Environ.Sci. Technol. 2004, 38 (20), 5379–5385.(8) Brede, E.;Wilhelm,M.; G€oen, T.;M€uller, J.; Rauchfuss, K.; Kraft,

M.; H€olzer, J. Two-year follow-up biomonitoring pilot study of resi-dents’ and controls’ PFC plasma levels after PFOA reduction in publicwater system in Arnsberg, Germany. Int. J. Hygiene Environ. Health 2010,213 (3), 217–223.(9) De Silva, A. O.; Mabury, S. A. Isolating isomers of perfluoro-

carboxylates in polar bears (Ursus maritimus) from two geographicallocations. Environ. Sci. Technol. 2004, 38 (24), 6538–6545.(10) Delinsky, A. D.; Strynar, M. J.; McCann, P. J.; Varns, J. L.;

McMillan, L.; Nakayama, S. F.; Lindstrom, A. B. Geographical distribu-tion of perfluorinated compounds in fish from Minnesota lakes andrivers. Environ. Sci. Technol. 2010, 44 (7), 2549–2554.(11) Houde, M.; Czub, G.; Small, J. M.; Backus, S.; Wang, X.; Alaee,

M.; Muir, D. C. G. Fractionation and bioaccumulation of perfluorooc-tane sulfonate (PFOS) isomers in a Lake Ontario food web. Environ. Sci.Technol. 2008, 42 (24), 9397–9403.(12) Smithwick, M.; Norstrom, R. J.; Mabury, S. A.; Solomon, K.;

Evans, T. J.; Stirling, I.; Taylor, M. K.; Muir, D. C. G. Temporal trends ofperfluoroalkyl contaminants in polar bears (Ursus maritimus) from two

locations in the North American Arctic, 1972�2002. Environ. Sci.Technol. 2006, 40 (4), 1139–1143.

(13) Yamashita, N.; Kannan, K.; Taniyasu, S.; Horii, Y.; Petrick, G.;Gamo, T. A global survey of perfluorinated acids in oceans.Mar. Pollut.Bull. 2005, 51 (8�12), 658–668.

(14) Rylander, C.; Sandanger, T. M.; Frøyland, L.; Lund, E. Dietarypatterns and plasma concentrations of perfluorinated compounds in 315Norwegian women: The NOWAC postgenome study. Environ. Sci.Technol. 2010, 44 (13), 5225–5232.

(15) Sundstr€om, M.; Ehresman, D. J.; Bignert, A.; Butenhoff, J. L.;Olsen, G. W.; Chang, S.-C.; Bergman, Å. A temporal trend study(1972�2008) of perfluorooctanesulfonate, perfluorohexanesulfonate,and perfluorooctanoate in pooled humanmilk samples from Stockholm,Sweden. Environ. Int. 2011, 37 (1), 178–183.

(16) Toms, L.-M. L.; Calafat, A.M.; Kato, K.; Thompson, J.; Harden,F.; Hobson, P.; Sj€odin, A.; Mueller, J. F. Polyfluoroalkyl chemicals inpooled blood serum from infants, children, and adults in Australia.Environ. Sci. Technol. 2009, 43 (11), 4194–4199.

(17) Weihe, P.; Kato, K.; Calafat, A. M.; Nielsen, F.; Wanigatunga,A. A.; Needham, L. L.; Grandjean, P. Serum concentrations of poly-fluoroalkyl compounds in faroese whale meat consumers. Environ. Sci.Technol. 2008, 42 (16), 6291–6295.

(18) Wilhelm, M.; Angerer, J.; Fromme, H.; Holzer, J. Contributionto the evaluation of reference values for PFOA and PFOS in plasma ofchildren and adults from Germany. Int. J. Hygiene Environ. Health 2009,212 (1), 56–60.

(19) Zhang, T.; Wu, Q.; Sun, H. W.; Zhang, X. Z.; Yun, S. H.;Kannan, K. Perfluorinated compounds in whole blood samples frominfants, children, and adults in China. Environ. Sci. Technol. 2010, 44(11), 4341–4347.

(20) Calafat, A.; Needham, L.; Kuklenyik, Z.; Reidy, J.; Tully, J.;Aguilarvillalobos, M.; Naeher, L. Perfluorinated chemicals in selectedresidents of the American continent. Chemosphere 2006, 63 (3), 490–496.

(21) Calafat, A. M.; Kuklenyik, Z.; Caudill, S. P.; Reidy, J. A.; Needham,L. L. Perfluorochemicals in pooled serum samples from United StatesResidents in 2001 and 2002. Environ. Sci. Technol. 2006, 40 (7), 2128–2134.

(22) Calafat, A. M.; Kuklenyik, Z.; Reidy, J. A.; Caudill, S. P.; Tully,J. S.; Needham, L. L. Serum Concentrations of 11 polyfluoroalkylcompounds in the U.S. population: Data from the National Healthand Nutrition Examination Survey (NHANES) 1999�2000. Environ.Sci. Technol. 2007, 41 (7), 2237–2242.

(23) Calafat, A. M.; Wong, L.-Y.; Kuklenyik, Z.; Reidy, J. A.; Needham,L. L. Polyfluoroalkyl chemicals in the U.S. population: Data from theNational Health and Nutrition Examination Survey (NHANES)2003�2004 and Comparisons with NHANES 1999�2000. Environ.Health Perspect. 2007, 115 (11), 1596–1602.

(24) De Silva, A. O.; Mabury, S. A. Isomer distribution of perfluoro-carboxylates in human blood: Potential correlation to source. Environ.Sci. Technol. 2006, 40 (9), 2903–2909.

(25) H€olzer, J.; Midasch, O.; Rauchfuss, K.; Kraft, M.; Reupert, R.;Angerer, J.; Kleeschulte, P.; Marschall, N.; Wilhelm, M. Biomonitoringof perfluorinated compounds in children and adults exposed to per-fluorooctanoate-contaminated drinking water. Environ. Health Perspect.2008, 116 (5), 651–657.

(26) Karrman, A.; Langlois, I.; Bavel, B.; Lindstrom, G.; Oehme, M.Identification and pattern of perfluorooctane sulfonate (PFOS) isomersin human serum and plasma. Environ. Inter. 2007, 33 (6), 782–788.

(27) Kuklenyik, Z.; Needham, L. L.; Calafat, A. M. Measurement of18 perfluorinated organic acids and amides in human serum using on-line solid-phase extraction. Anal. Chem. 2005, 77 (18), 6085–6091.

(28) Olsen, G. W.; Huang, H.-Y.; Helzlsouer, K. J.; Hansen, K. J.;Butenhoff, J. L.; Mandel, J. H. Historical comparison of perfluoroocta-nesulfonate, perfluorooctanoate, and other fluorochemicals in humanblood. Environ. Health Perspect. 2005, 113 (5), 539–545.

(29) Melzer, D.; Rice, N.; Depledge,M.H.; Henley,W. E.; Galloway,T. S. Association between serum perfluorooctanoic acid (PFOA) andthyroid disease in the U.S. National Health and Nutrition ExaminationSurvey. Environ. Health Perspect. 2010, 118 (5), 686–692.



(30) Kishi, R.; Nakazawa, H.; Saito, K.; Iwasaki, Y.; Nakata, A.;Ito, R.; Konishi, K.; Ban, S.; Kato, S.; Sasaki, S.; Saijo, Y.; Washino,N. Correlations between prenatal exposure to perfluorinated chemicalsand reduced fetal growth. Environ. Health Perspect. 2008, 117, 660–667.(31) Lau, C.; Butenhoffb, J. L.; Rogersa, J. M. The developmental

toxicity of perfluoroalkyl acids and their derivatives. Toxicol. Appl.Pharmacol. 2004, 198 (2), 231–241.(32) Inoue, K.; Okada, F.; Ito, R.; Kato, S.; Sasaki, S.; Nakajima, S.;

Uno, A.; Saijo, Y.; Sata, F.; Yoshimura, Y.; Kishi, R.; Nakazawa, H.Perfluorooctane sulfonate (PFOS) and related perfluorinated com-pounds in human maternal and cord blood samples: Assessment ofPFOS exposure in a susceptible population during pregnancy. Environ.Health Perspect. 2004, 112 (11), 1204–1207.(33) K€arrman, A.; Ericson, I.; van Bavel, B.; Darnerud, P. O.; Aune,

M.; Glynn, A.; Lignell, S.; Lindstr€om, G. Exposure of perfluorinatedchemicals through lactation: Levels of matched human milk and serumand a temporal trend, 1996�2004, in Sweden. Environ. Health Perspect.2006, 115 (2), 226–230.(34) von Ehrenstein, O. S.; Fenton, S. E.; Kato, K.; Kuklenyik, Z.;

Calafat, A. M.; Hines, E. P. Polyfluoroalkyl chemicals in the serum andmilk of breastfeeding women. Reprod. Toxicol. 2009, 27 (3�4),239–245.(35) Spliethoff, H. M.; Tao, L.; Shaver, S. M.; Aldous, K. M.; Pass,

K. A.; Kannan, K.; Eadon, G. A. Use of newborn screening programblood spots for exposure assessment: declining levels of perfluorinatedcompounds in New York state infants. Environ. Sci. Technol. 2008, 42,5361–5367.(36) Health and Environmental Assessment of Perfluorooctane Sulfonic

Acid and Its Salts, U.S. EPA Docket AR-226-1486; 3M Company: St.Paul, MN, 2003.(37) Dinglasan, M. J. A.; Ye, Y.; Edwards, E. A.; Mabury, S. A.

Fluorotelomer alcohol biodegradation yields poly- and perfluorinatedacids. Environ. Sci. Technol. 2004, 38 (10), 2857–2864.(38) Ellis, D. A.; Martin, J. W.; De Silva, A. O.; Mabury, S. A.; Hurley,

M. D.; Sulbaek Andersen, M. P.; Wallington, T. J. Degradation offluorotelomer alcohols: A likely atmospheric source of perfluorinatedcarboxylic acids. Environ. Sci. Technol. 2004, 38 (12), 3316–3321.(39) Tomy, G. T.; Tittlemier, S. A.; Palace, V. P.; Budakowski, W. R.;

Braekevelt, E.; Brinkworth, L.; Friesen, K. Biotransformation of N-ethylperfluorooctanesulfonamide by rainbow trout (Onchorhynchus mykiss)liver microsomes. Environ. Sci. Technol. 2003, 38 (3), 758–762.(40) Sinclair, E.; Kim, S. K.; Akinleye, H. B.; Kannan, K. Quantita-

tion of gas-phase perfluoroalkyl surfactants and fluorotelomer alcoholsreleased from nonstick cookware and microwave popcorn bags. Environ.Sci. Technol. 2007, 41 (4), 1180–1185.(41) Nilsson, H.; K€arrman, A.; Westberg, H.; Rotander, A.; van

Bavel, B.; Lindstr€om, G. A time trend study of significantly elevatedperfluorocarboxylate levels in humans after using fluorinated ski wax.Environ. Sci. Technol. 2010, 44 (6), 2150–2155.(42) Haug, L. S.; Thomsen, C.; Becher, G. Time trends and the

influence of age and gender on serum concentrations of perfluorinatedcompounds in archived human samples. Environ. Sci. Technol. 2009,43 (6), 2131–2136.(43) Olsen, G. W.; Mair, D. C.; Reagen, W. K.; Ellefson, M. E.;

Ehresman, D. J.; Butenhoff, J. L.; L.R., Z. Preliminary evidence of adecline in perfluorooctanesultonate (PFOS) and perfluorooctaneoate(PFOA) concentrations in American Red Cross blood donors. Chemo-sphere 2007, 68, 105–111.(44) Sturm, R.; Ahrens, L. Trends of polyfluoroalkyl compounds in

marine biota and in humans. Environ. Chem. 2010, 7, 457–484.(45) Holmstr€om, K. E.; J€arnberg, U.; Bignert, A. Temporal trends of

PFOS and PFOA in guillemot eggs from the baltic sea, 1968�2003.Environ. Sci. Technol. 2005, 39 (1), 80–84.(46) Kuklenyik, Z.; Reich, J. A.; Tully, J. S.; Needham, L. L.; Calafat,

A. M. Automated solid-phase extraction and measurement of perfluori-nated organic acids and amides in human serum and milk. Environ. Sci.Technol. 2004, 38 (13), 3698–3704.

(47) Van den Berg, B. J. The California Child Health and Develop-ment Studies: Twenty years of research. World Health Stat. Q. 1979,32, 269–286.

(48) M.R., W.; Petrakis, N. L.; R., M.; E.B., K.; K., C.; J., N.; M.M., L.;M., R. Breast Cancer risk in women with abnormal cytology in nippleaspirates of breast fluid. J. Natl. Cancer Inst. 2001, 93 (23), 1791–1798.

(49) OEHHA Office of Environmental Health Hazard Accessment,http://www.oehha.ca.gov/multimedia/biomon/index.html (accessed).

(50) Keller, J. M.; Calafat, A. M.; Kato, K.; Ellefson, M. E.; Reagen,W. K.; Strynar, M.; O’Connell, S.; Butt, C. M.; Mabury, S. A.; Small, J.;Muir, D. C. G.; Leigh, S. D.; Schantz, M. M. Determination ofperfluorinated alkyl acid concentrations in human serum and milkstandard reference materials. Anal. Bioanal. Chem. 2009, 397 (2),439–451.

(51) Cuzick, J. A Wilcoxon-type test for trend. Stat. Med. 1985,4, 87–90.

(52) Taves, D. R. Evidence that there are Two Forms of Fluoride inHuman Serum. Nature 1968, 217, 1050–1051.

(53) Olsen, G. W.; Burris, J. M.; Ehresman, D. J.; Froehlich, J. W.;Seacat, A. M.; Butenhoff, J. L.; Zobel, L. R. Half-life of serum eliminationof perfluorooctanesulfonate,perfluorohexanesulfonate, and perfluorooc-tanoate in retired fluorochemical production workers. Environ. HealthPerspect. 2007, 115 (9), 1298–1305.

(54) Tatum-Gibbs, K.; Wambaugh, J. F.; Das, K. P.; Zehr, R. D.;Strynar, M. J.; Lindstrom, A. B.; A., D.; C., L. Comparative pharmaco-kinetics of perfluorononanoic acid in rat and mouse. Toxicology 2011,281 (1�3), 48–55.

(55) Ohmori, K.; Kudo, N.; Katayama, K.; Y., K. Comparison of thetoxicokinetics between perfluorocarboxylic acids with different carbonchain length. Toxicology 2003, 184 (2�3), 135–140.

(56) T.J., W.; A.R., Z.; J.M., S., Environmental chemicals in pregnantwomen in the US: NHANES 2003�2004. Environ. Health Perspect.2011, DOI:10.1289, ehp.1002727.

(57) Tao, L.; Kannan, K.;Wong, C.M.; Arcaco, K. F.; Butenhoff, J. L.Perfluorinated compounds in human milk from Massachusetts, U.S.A.Environ. Sci. Technol. 2008, 42, 3096–3101.

Temporal Changes in the Levels of Perfluorinated Compounds in California Women's Serum over the Past...

Documents

Transcript of Temporal Changes in the Levels of Perfluorinated Compounds in California Women's Serum over the Past...