A Pilot Survey of Legacy and Current Commercial Fluorinated

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A Pilot Survey of Legacy and Current Commercial Fluorinated Chemicals in Human Sera from United States Donors in 2009 Holly Lee and Scott A. Mabury* Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada, M5S 3H6

bS Supporting Information ABSTRACT: Human biomonitoring has traditionally focused on analyzing the perfluorocarboxylates (PFCAs) and perfluorosulfonates (PFSAs), although the presence of other unidentified fluorinated chemicals has been demonstrated through total organofluorine analysis. Exposure to legacy and current commercial fluorinated chemicals was investigated by analyzing fifty human sera samples collected in 2009 from the United States for forty fluorinated analytes that included the polyfluoroalkyl phosphate diesters (diPAPs), N-ethyl perfluorooctanesulfonamidoethanol-based polyfluoroalkyl phosphate diester (SAmPAP), one fluorotelomer mercaptoalkyl phosphate diester congener (FTMAP), fluorotelomer sulfonates (FTSs), perfluorophosphonates (PFPAs), and perfluorophosphinates (PFPiAs). DiPAP concentrations (0.035
0.136 μg/L) for the more dominant congeners (6:2, 6:2/8:2, 8:2) were lower than those reported in human sera samples collected in 2004, 2005, and 2008. The SAmPAP and 6:2 FTMAP were not detected, but exposure to SAmPAP was suggested based on the detection of one of its potential degradation intermediates, N-ethyl perfluorooctanesulfonamidoacetate (N-EtFOSAA). PFPiAs were detected for the first time in human sera, with C6/C6 and C6/C8 PFPiAs as the dominant congeners, observed in >50% of the samples.

’ INTRODUCTION Perfluorocarboxylates (PFCAs) and perfluorosulfonates (PFSAs) have been observed at μg/L concentrations in human blood worldwide.1
7 The profile in human sera is typically dominated by perfluorooctanesulfonate (PFOS, C8 PFSA), followed by perfluorooctanoate (PFOA, C8 PFCA) and perfluorohexanesulfonate (PFHxS, C6 PFSA). One potential source of this contamination is the metabolic transformation of commercial fluorinated materials into the PFCAs and PFSAs. Fluorochemical production in North America has largely proceeded by electrochemical fluorination (ECF) to produce perfluoroalkylsulfonamides (PFSAms) and telomerization to produce fluorotelomer-based materials.8 After 3M announced the phase-out of their perfluorooctylsulfonyl (POSF)-based materials in 2000, with production ceasing entirely in 2002,9 telomerization became the dominant manufacturing process of fluorochemicals in North America.10 The PFSAm- and fluorotelomer-based starting raw materials produced from these two processes are incorporated into polymers and surfactants for applications, such as treating surfaces of fabrics, carpets, and textiles; greaseproofing food contact papers; and leveling and wetting agents. Fluorinated phosphate surfactants are used as greaseproofing agents in food contact papers11 and have a demonstrated potential to migrate into food.12,13 The N-ethyl perfluorooctanesulfonamidoethanol (N-EtFOSE)-based polyfluoroalkyl phosphate esters (SAmPAPs) were used in food contact paper during the r 2011 American Chemical Society

period of 1974
20002,14 until their production ceased after the phase-out of POSF chemistries.9 Human exposure to SAmPAP is consistent with the observed increase of N-ethyl perfluorooctanesulfonamidoacetate (N-EtFOSAA) in human blood from 1974 to 1989.4
6 Biotransformation of N-EtFOSE to PFOS has been observed in rat liver microsomes, cytosol fractions, and liver slices,15 and so SAmPAP may also represent a source of human exposure to PFOS exposure. A family of fluorotelomer-based phosphate surfactants, the polyfluoroalkyl phosphate diesters (diPAPs), was recently discovered at μg/L concentrations in human sera.16 DiPAPs are established biological precursors of PFCAs in microbial and mammalian systems.17
19 As biotransformation to PFCAs may be possible from any fluorotelomer backbone, research on exposure to other types of fluorotelomer-based materials is warranted. The fluorotelomer mercaptoalkyl phosphate esters (FTMAPs) have been commercialized for use in food packaging in the United States (U.S.) since 1995.20
22 Little is known about the potential for human exposure and the environmental Special Issue: Perfluoroalkyl Acid Received: January 14, 2011 Accepted: March 30, 2011 Revised: March 24, 2011 Published: April 12, 2011 8067

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Environmental Science & Technology fate of these telomer-based phosphate surfactants. One possible fate is enzyme-mediated cleavage of the carbon
sulfur (C
S) bond in the perfluoroalkylethylthio moiety to produce the fluorotelomer sulfonates (FTSs). FTS concentrations have been observed to increase from influent to effluent in 4 of 10 wastewater treatment plants (WWTP) studied.23 This increase was potentially due to biodegradation of any precursors containing a perfluoroalkylethylthio moiety. Significant groundwater contamination of FTSs (up to 14 600 μg/L) near fire-training facilities has been attributed to the degradation of fluoroalkylthioamido sulfonates (CF3(CF2)nCH2CH2SCH2CH2CONHC(CH3)2CH2SO3
) in aqueous film-forming foams (AFFFs) used at these sites.24 Given that FTSs have been shown to biodegrade to the PFCAs,25,26 the FTMAPs may represent a potential new source of PFCAs to humans. Perfluorophosphonates (PFPAs) and perfluorophosphinates (PFPiAs) are fluorinated surfactants used as leveling and wetting agents in waxes and coatings, and as defoaming agents in pesticide formulations.27,28 However, in 2006, these chemicals were delisted as ingredients allowed in pesticide formulations in the U.S. and effectively banned from this application starting in 2008.29 Widespread contamination of PFPAs was observed in 80% of Canadian surface waters and WWTP effluents sampled.30 The C6/C6 and C6/C8 PFPiAs were also detected at ∼2 ng/g concentrations in a WWTP sludge sample.31 Oral gavage experiments revealed that the elimination half-lives for these chemicals in rats (1
9 days) may potentially translate to significant halflives in humans.31 Given their prevalence in the environment, there is the potential for human exposure to PFPAs and PFPiAs. Commercial products are largely composed of fluorinated polymers and/or surfactants with percent quantities of residual PFSAm or fluorotelomer starting materials present.11,27,32,33 In contrast, PFCAs and PFSAs have only been observed as trace (ppb) contaminants in commercial products.12,34 Previous analyses of the total extractable organofluorine fraction in human blood revealed that known fluorinated chemicals, such as the PFCAs and PFSAs, may not fully account for the total contamination observed.35 This suggests the presence of other unidentified fluorinated chemicals. In this study, fifty North American blood samples were analyzed for forty different fluorinated analytes that included commercial fluorinated surfactants, residual materials, degradation intermediates, and final PFCAs and PFSAs degradation products. This investigation is the first to examine human sera for the SAmPAP, one FTMAP congener, PFPAs, and PFPiAs.

’ MATERIALS AND METHODS Chemicals. A list of all standards and reagents used in this study is provided in the Supporting Information (SI). Structures, full names, and acronyms of the target analytes are shown in Table 1. DiPAPs (y = x) and 6:2 FTMAP were synthesized by methods described in the SI. Due to a lack of authentic standards for the PFPiAs at the time of analysis, the Masurf 780 technical product was used for quantitation. Purity of the synthesized diPAPs (y = x) and the chemical composition of the Masurf were determined using analytical standards (6:2, 8:2, 10:2 diPAPs; C6/C6, C6/C8, and C8/C8 PFPiAs) that became available after the analysis of all samples, as described in the SI. Sera Samples. Fifty human sera samples were obtained from Golden West Biologicals, Inc. (Temecula, CA). The samples

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were collected in the U.S. in 2009 from donors varying in age (18
70 years old) and gender. Twenty samples were from individual male donors and twenty were from individual female donors. The remaining ten 2009 samples were pooled samples in which each sample pool consisted of at least ten individual donors, with no overlap in donors between each pooled sample. The rationale for analyzing both sample types is discussed in the SI. Calf serum was purchased from Sigma Aldrich (Oakville, ON) for use as a recovery matrix. Sera samples were stored at
20 °C prior to extraction. A human serum standard reference material (SRM 1957: Organic Contaminants in Non-Fortified Human Serum) was obtained from the National Institute of Standards and Technology (NIST) and analyzed for quality control. Extractions and Instrumental Analysis. The sera samples (2
3 mL) were extracted using modified versions of the ionpairing method developed by Hansen et al.1 Detailed extraction procedures, chromatographic gradients, instrumental conditions, and multiple reaction monitoring (MRM) mass transitions are provided in the SI. Quality Assurance of Data. The C4
C14 PFCAs, C4, C6, C8, and C10 PFSAs, perfluorooctanesulfonamidoacetate (FOSAA), N-methyl perfluorooctanesulfonamidoacetate (NMeFOSAA), and N-EtFOSAA were quantified using masslabeled internal standards (Table S2). The diPAPs (y = x), PFPAs, PFPiAs, FTSs, SAmPAP, and 6:2 FTMAP were quantified by standard addition as no internal standards were available at the time of analysis. As no standards were synthesized for the mixed diPAPs (y = x þ 2), they were quantified as described previously,16 in which the standard additions of the adjacent y = x diPAPs were used as matrix-matched standards. Chromatograms of a standard addition analysis of a human sera sample for the PFPiAs are provided in the SI. Spike and recovery experiments were performed in triplicate by adding 1 ng of each of the target analytes into the calf serum recovery matrix, and the samples were extracted and analyzed as described in the SI. Analyte recoveries were corrected for background concentrations present in the unspiked matrix and ranged from 71 to 125% (Table S3ab). Of the 36 analytes measured, ∼80% of the recoveries were within 10% of the spiked concentrations. The reported concentrations in the human sera samples were not corrected for recovery. The limits of detection (LOD) and limits of quantitation (LOQ) were defined as the concentrations producing a signal-tonoise (S/N) ratio of equal to or greater than 3 and 10, respectively. The method LOD and LOQ values for each analyte are listed in Table S3ab. Values below the LOD were reported as nondetect (nd). For the purposes of calculating means, values below the LOD were assigned a value of zero and values below the LOQ were used unaltered. All reported concentrations are presented as arithmetic means with standard error. Each human sera sample was extracted in duplicate with one procedural blank (HPLC grade water) extracted in company to each sample (n = 50). The procedural blanks (n = 50) were analyzed to check for contamination during the extractions. The average relative standard errors for the duplicate analysis of sera samples observed at concentrations above the analyte-specific method LOQ were in the range of 11
36% for analytes quantified by standard addition and 3
24% for analytes quantified using internal standards. Few analytes were detected in the blanks, and when detected, their concentrations were consistently below the analyte-specific LOQs, with the exception of PFHxA (0.011 ( 0.007 μg/L), PFHpA (0.008 ( 0.004 μg/L), 8068

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Environmental Science & Technology

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Table 1. Structures, Full Names, and Acronyms of the Target Analytes

and PFOA (0.011 ( 0.004 μg/L). The sera concentrations for these analytes are at least 1 order of magnitude higher than their corresponding LOQs. Analysis of methanol rinses of items used for blood collection by the commercial supplier showed no contamination by any of the target analytes, except for PFOA and 6:2 diPAP, which were observed at concentrations below their corresponding instrumental LOQs. Details of the rinse procedure are described in the SI. The methods used in this study were evaluated by analyzing the NIST SRM 1957 serum sample and comparing the concentrations of the C7
C11 PFCAs, PFHxS, and PFOS to those reported on the certificate of analysis and in an interlaboratory study.36 The SRM sample was also analyzed for the full suite of analytes monitored in this study and the data set is provided in Table S4ab. The percent errors of the concentrations measured in the serum SRM were 20% of the single donor and pooled human sera samples. Note: Analytes denoted with an asterisk (*) were detected in