Avoiding Regrettable Replacements: Can the Introduction of Novel Functional Groups Move PFAS from Recalcitrant to Reactive?

Per- and polyfluoroalkyl substances (PFASs) are present in a range of commercial and consumer products. These chemicals are often high-performance surfactants or nonstick/water-repellant coatings due to their chemical stability; however, this stability leads to select PFAS being environmentally persistent. To facilitate degradation, new fluorosurfactant building blocks (F7C3-O-CHF-CF2-S-CH2-CH2-OH (FESOH), F3C-O-CHF-CF2-S-CH2-CH2-OH (MeFESOH), F7C3-O-CHF-CF2-O-CH2-CH2-OH (ProFdiEOH), F7C3-O-CHF-CF2-CH2-OH (ProFEOH), and F3C-O-CHF-CF2-O-CH2-CH2-OH (MeFdiEOH)) have been systematically developed with heteroatom linkages such as ethers, thioethers, and polyfluorinated carbons. The room temperature, gas-phase OH oxidation rate constants, and products of these chemicals were monitored in an atmospheric chamber to investigate their fate in the atmosphere. Analysis was performed using online high-resolution chemical ionization mass spectrometry (CIMS) using the iodide reagent ion and via offline UPLC-MS/MS. FESOH and MeFESOH, the thioether congeners, were observed to have the largest rate constants of kFESOH = 2.82 (±0.33) and kMeFESOH = 2.17 (±0.17) (×10-12 cm3 molecules-1 s-1, respectively). First-, second-, and third-generation products of OH oxidation were observed as a function of time, while product quantification yielded ultrashort perfluoropropionic acid (PFPrA) and short polyfluoroether acid species as the terminal products for FESOH and ProFdiEOH. There was evidence for MeFESOH being fully mineralized, demonstrating the potential benign chemical architecture.

Occurrence, Fate, Human Exposure, and Toxicity of Commercial Photoinitiators.

Photoinitiators (PIs) are a family of anthropogenic chemicals used in polymerization systems that generate active substances to initiate polymerization reactions under certain radiations. Although polymerization is considered a green method, its wide application in various commercial products, such as UV-curable inks, paints, and varnishes, has led to ubiquitous environmental issues caused by PIs. In this study, we present an overview of the current knowledge on the environmental occurrence, human exposure, and toxicity of PIs and provide suggestions for future research based on numerous available studies. The residual concentrations of PIs in commercial products, such as food packaging materials, are at microgram per gram levels. The migration of PIs from food packaging materials to foodstuffs has been confirmed by more than 100 reports of food contamination caused by PIs. Furthermore, more than 20 PIs have been detected in water, sediment, sewage sludge, and indoor dust collected from Asia, the United States, and Europe. Human internal exposure was also confirmed by the detection of PIs in serum. In addition, PIs were present in human breast milk, indicating that breastfeeding is an exposure pathway for infants. Among the most available studies, benzophenone is the dominant congener detected in the environment and humans. Toxicity studies of PIs reveal multiple toxic end points, such as carcinogenicity and endocrine-disrupting effects. Future investigations should focus on synergistic/antagonistic toxicity effects caused by PIs coexposure and metabolism/transformation pathways of newly identified PIs. Furthermore, future research should aim to develop "greener" PIs with high efficiency, low migration, and low toxicity.

Noise-Reduced Quantitative Fluorine NMR Spectroscopy Reveals the Presence of Additional Per- and Polyfluorinated Alkyl Substances in Environmental and Biological Samples When Compared with Routine Mass Spectrometry Methods.

Per- and polyfluorinated alkyl substances (PFAS) are ubiquitous throughout the environment. Analysis of PFAS is commonly performed using both targeted and nontargeted mass spectrometry methods. However, it has been demonstrated that measurements of fluorinated compounds in the environment by mass spectrometry often fall short of the total fluorine concentration. In the present study, we employ a 19F NMR technique, which is capable of detailing fluorinated compounds in a sample while providing both quantitative and structural information. Inclusion of a noise-reduction strategy involving the acquisition of arrays of spectra with an increasing number of transients addresses the sensitivity challenges of environmental nuclear magnetic resonance (NMR), improving signal to noise. When this technique is applied to environmental and biological samples including rainwater, lake water, wastewater effluent, serum, and urine, the presence of PFAS, which may have been missed by routine mass spectrometric methods, is revealed. Important resonances in the 19F NMR spectrum such as that of trifluoroacetic acid are brought above the limit of quantification in all samples, allowing detection limits as low as 389 pg/L in rainwater. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which was used to analyze 47 PFAS compounds, accounts for only 3.7-27% of the total fluorine concentration as determined by the NMR strategy in the present study.

Significant Reductive Transformation of 6:2 Chlorinated Polyfluorooctane Ether Sulfonate to Form Hydrogen-Substituted Polyfluorooctane Ether Sulfonate and Their Toxicokinetics in Male Sprague-Dawley Rats.

6:2 chlorinated polyfluorooctane ether sulfonate (6:2 Cl-PFESA) was previously shown to undergo limited dechlorination in rainbow trout to yield 6:2 hydrogen-substituted polyfluorooctane ether sulfonate (6:2 H-PFESA) as the sole metabolite. However, the biotransformation susceptibility of 6:2 Cl-PFESA has not been investigated in mammals and the biological behavior of 6:2 H-PFESA has not been defined in any species. We investigated the respective transformation products of 6:2 Cl-PFESA and 6:2 H-PFESA and their toxicokinetic properties in male Sprague-Dawley rats as a mammalian model. 6:2 H-PFESA was the sole detectable metabolite of 6:2 Cl-PFESA, with a transformation percentage of 13.6% in rat liver, but it resisted further degradation. 6:2 Cl-PFESA also transformed to 6:2 H-PFESA in reductive rat liver S9 incubations but remained stable under oxidative conditions, suggesting a reductive enzyme-dependent transformation pathway. 6:2 Cl-PFESA was more enriched in lipid-rich tissues, while 6:2 H-PFESA was more prone to cumulative urinary excretion. From this perspective, it may suggest a detoxification mechanism for organisms to form the less hydrophobic 6:2 H-PFESA to alleviate total burdens. To date, 6:2 Cl-PFESA was the second perfluoroalkyl acid reported to undergo biotransformation in mammals. The toxicokinetic properties determined for 6:2 Cl-PFESA and 6:2 H-PFESA in blood and urine were found to be structure and dose dependent.

Anaerobic Microbial Dechlorination of 6:2 Chlorinated Polyfluorooctane Ether Sulfonate and the Underlying Mechanisms.

The microbial transformation potential of 6:2 chlorinated polyfluorooctane ether sulfonate (6:2 Cl-PFESA) was explored in anaerobic microbial systems. Microbial communities from anaerobic wastewater sludge, an anaerobic digester, and anaerobic dechlorinating cultures enriched from aquifer materials reductively dechlorinated 6:2 Cl-PFESA to 6:2 hydrogen-substituted polyfluorooctane ether sulfonate (6:2 H-PFESA), which was identified as the sole metabolite by non-target analysis. Rapid and complete reductive dechlorination of 6:2 Cl-PFESA was achieved by the anaerobic dechlorinating cultures. The microbial community of the anaerobic dechlorinating cultures was impacted by 6:2 Cl-PFESA exposure. Organohalide-respiring bacteria originally present in the anaerobic dechlorinating cultures, including Geobacter, Dehalobacter, and Dehalococcoides, decreased in relative abundance over time. As the relative abundance of organohalide-respiring bacteria decreased, the rates of 6:2 Cl-PFESA dechlorination decreased, suggesting that the most likely mechanism for reductive dechlorination of 6:2 Cl-PFESA was co-metabolism rather than organohalide respiration. Reductive defluorination of 6:2 Cl-PFESA was not observed. Furthermore, 6:2 H-PFESA exhibited 5.5 times lower sorption affinity to the suspended biosolids than 6:2 Cl-PFESA, with the prospect of increased mobility in the environment. These results show the susceptibility of 6:2 Cl-PFESA to microbially mediated reductive dechlorination and the likely persistence of the product, 6:2 H-PFESA, in anaerobic environments.

Atmospheric Fate of a New Polyfluoroalkyl Building Block, C3F7OCHFCF2SCH2CH2OH.

Many per- and polyfluoroalkyl substances (PFAS) have been regulated or phased-out of usage due to concerns about persistence, bioaccumulation potential, and toxicity. We investigated the atmospheric fate of a new polyfluorinated alcohol 2-(1,1,2-trifluoro-2-heptafluoropropyloxy-ethylsulfanyl)-ethanol (C3F7OCHFCF2SCH2CH2OH, abbreviated FESOH) by assessing the kinetics and products of the gas-phase reaction of FESOH with chlorine atoms and hydroxyl radicals. Experiments performed in a stainless-steel chamber interfaced to an FTIR were used to determine reaction kinetics and gas-phase products. We report reaction rate constants of k(Cl + FESOH) = (1.5 ± 0.6) × 10-11 cm3 molecule-1 s-1 and k(OH + FESOH) = (4.2 ± 2.0) × 10-12 cm3 molecule-1 s-1. This leads to a calculated FESOH gas-phase lifetime of 2.8 ± 1.3 days with respect to reaction with OH, assuming [OH] = 106 molecule1 cm-3. Gas-phase products of FESOH oxidation included at least two aldehydes, likely C3F7OCHFCF2SCH2C(O)H and C3F7OCHFCF2SC(O)H, and secondary products including COF2, SO2 and C3F7OC(O)F. Additional gas-phase experiments performed in a Teflon chamber were used to assess aqueous products by collecting gaseous samples offline into an aqueous sink prior to analysis with ultrahigh performance liquid chromatography-tandem mass spectrometry, resulting in four acidic products: C3F7OCHFCF2SCH2C(O)OH, C3F7OCHFCF2S(O)(O)OH, C3F7OCHFC(O)OH, and perfluoropropanoic acid (C2F5C(O)OH).

Rat Metabolism Study Suggests 3-(3,5-Di-tert-butyl-4-hydroxyphenyl)propionic Acid as a Potential Urinary Biomarker of Human Exposure to Representative 3-(3,5-Di-tert-butyl-4-hydroxyphenyl)propionate Antioxidants.

3-(3,5-Di-tert-butyl-4-hydroxyphenyl)propionate antioxidants, a family of synthetic phenolic antioxidants (SPAs) widely used in polymers, have recently been identified in indoor and outdoor environments. However, limited information is available concerning human exposure to these novel contaminants. In the present study, seven 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate antioxidants were analyzed in human urine samples of donors from the United States. None of the target SPAs were initially detected in the urine samples either before or after hydrolysis by ß-glucuronidase, prompting us to probe the major metabolites of these SPAs. We conducted rat metabolism studies with two representative congeners, tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate) (AO1010) and N,N'-bis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionyl]hydrazine (AO1024). Neither AO1010 nor AO1024 was detected in rat urine, while 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionic acid (fenozan acid) was identified as a urinary biomarker for these 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate antioxidants. Surprisingly, fenozan acid was detected in 88% of the human urine samples before hydrolysis (geometric mean: 0.69 ng/mL) and 98% of the samples after hydrolysis (geometric mean: 10.2 ng/mL), indicating prevalent human exposure to 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate antioxidants. To our knowledge, this is the first study reporting the occurrence of fenozan acid in urine, where it can act as a potential biomarker of human exposure to 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate antioxidants.

Synthetic Phenolic Antioxidants: A Review of Environmental Occurrence, Fate, Human Exposure, and Toxicity.

Synthetic phenolic antioxidants (SPAs) are widely used in various industrial and commercial products to retard oxidative reactions and lengthen product shelf life. In recent years, numerous studies have been conducted on the environmental occurrence, human exposure, and toxicity of SPAs. Here, we summarize the current understanding of these issues and provide recommendations for future research directions. SPAs have been detected in various environmental matrices including indoor dust, outdoor air particulates, sea sediment, and river water. Recent studies have also observed the occurrence of SPAs, such as 2,6-di-tert-butyl-4-methylphenol (BHT) and 2,4-di-tert-butyl-phenol (DBP), in humans (fat tissues, serum, urine, breast milk, and fingernails). In addition to these parent compounds, some transformation products have also been detected both in the environment and in humans. Human exposure pathways include food intake, dust ingestion, and use of personal care products. For breastfeeding infants, breast milk may be an important exposure pathway. Toxicity studies suggest some SPAs may cause hepatic toxicity, have endocrine disrupting effects, or even be carcinogenic. The toxicity effects of some transformation products are likely worse than those of the parent compound. For example, 2,6-di-tert-butyl-p-benzoquinone (BHT-Q) can cause DNA damage at low concentrations. Future studies should investigate the contamination and environmental behaviors of novel high molecular weight SPAs, toxicity effects of coexposure to several SPAs, and toxicity effects on infants. Future studies should also develop novel SPAs with low toxicity and low migration ability, decreasing the potential for environmental pollution.

First Report on In Vivo Pharmacokinetics and Biotransformation of Chlorinated Polyfluoroalkyl Ether Sulfonates in Rainbow Trout.

This study provides the first in vivo pharmacokinetic data for chlorinated perfluorooctanesulfonate (Cl-PFOS), 6:2 and 8:2 chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESAs), upon a 30 day dietary exposure and 34 day depuration phase in rainbow trout (Oncorhynchus mykiss). Biological handling of these three novel molecules and legacy PFOS were investigated via cross-comparison. PFOS and Cl-PFOS displayed comparable bioaccumulative potencies and similar distribution tendencies in tissues (blood > liver > kidneys), despite the presence of a terminal chlorine atom in Cl-PFOS molecule. The Cl-PFESAs, especially 8:2 Cl-PFESA, were predominantly assimilated from the bloodstream by liver and kidneys and resisted elimination, leading to higher bioaccumulation factors in liver than in blood (0.576 and 0.254, respectively, for 8:2 Cl-PFESA) and longer half-lives in liver and kidneys than PFOS, suggesting these alternatives may pose greater risks in terms of the great accumulation potentials in fish tissues. The present study provides the first report of the in vivo transformation of 6:2 and 8:2 Cl-PFESAs and identifies 6:2 and 8:2 H-PFESAs as their respective sole metabolites. This provides the first line of evidence suggesting that the transformation susceptibility of Cl-PFESAs in organisms is distinct from their environmental persistence.

Organophosphite Antioxidants in Indoor Dust Represent an Indirect Source of Organophosphate Esters.

Precise determination of organophosphate esters (OPEs) in the environment is crucial to estimating their potential toxicity effects on human health. Previous studies have mainly focused on OPEs from direct sources. This study explored a potential indirect source of OPEs: the oxidation of organophosphite antioxidants (OPAs). OPAs are frequently used to retard degradation in polymers through their oxidation to OPEs. In this work, five OPAs [tris(2-chloroethyl) phosphite, triphenyl phosphite, tris(2,4-di- tert-butylphenyl) phosphite, bis(2,4-di- tert-butylphenyl) pentaerythritol diphosphite, and trisnonylphenol phosphite] could be identified, with geometric mean (GM) concentrations from 2.46 to 70.4 ng/g, in indoor dust. Their oxidation products, triisodecyl phosphate (TiDeP), tris(2,4-di- tert-butylphenyl) phosphate (AO168═O), bis(2,4-di- tert-butylphenyl) pentaerythritol diphosphate (AO626═O2), and trisnonylphenol phosphate (TNPP), were found at significantly higher GM concentrations (30.5-3759 ng/g). Surprisingly, two novel oxidation products AO168═O (GM: 3759 ng/g) and TNPP (GM: 2185 ng/g) had higher concentrations than tris(2-chloroethyl) phosphate (GM: 1608 ng/g) and triphenyl phosphate (GM: 1827 ng/g), which are well-known OPEs. These four novel OPEs (TiDeP, TNPP, AO168═O, AO626═O2) contributed 54.1% to the total concentration of the eight OPEs. The present investigation demonstrates that oxidation of OPAs is an important indirect source of novel OPEs in indoor environments. This is the first detection of four OPAs and their newly identified OPE oxidation products in indoor dust.

Identification of Photoinitiators, Including Novel Phosphine Oxides, and Their Transformation Products in Food Packaging Materials and Indoor Dust in Canada.

Although photopolymerization is generally considered a green technology, the contamination of foodstuffs by photoinitiators (PIs), an essential component of photopolymerization systems, has recently attracted notice. Despite this interest, little attention has been paid to PI contamination in the environment. To date, only one study, performed in China, has reported the occurrence of PIs in the environment. In the present study, the occurrence of 25 PI additives with discrete molecular structures was investigated in food packaging materials and indoor dust. The PIs studied here include benzophenones (BZPs), thioxanthones (TXs), amine co-initiators (ACIs), and novel phosphine oxides (POs). Twenty-four PIs were detected in food packaging materials. Total concentrations of PIs (∑PIs) ranged between 122 and 44 113 ng/g, with a geometric mean (GM) of 3375 ng/g. The photodegradation of PIs in food packaging materials was investigated for the first time, and the half-lives of PIs in these materials were found to range from 32 to 289 h. These 24 PIs were also detected in indoor dust samples (GM of ∑PIs = 1483 ng/g). The relative abundances of different PIs were found to vary between the packaging materials and the indoor dust, which is attributed in part to the different stabilities of different PIs under simulated sunlight. Using standards synthesized in our lab, four TX transformation products (GM: 34.8 ng/g) were also detected in indoor dust. The concentrations of the transformation products were higher than the concentrations of the parent chemicals in indoor dust. Thus, further studies exploring human exposure to TXs should include these transformation products to avoid underestimation. This is the first report of PIs and relevant transformation products in the indoor environment in North America.

Synthetic Phenolic Antioxidants in Personal Care Products in Toronto, Canada: Occurrence, Human Exposure, and Discharge via Greywater.

Although synthetic phenolic antioxidants (SPAs) are widely used in various personal care products (PCPs), little is known about their levels, composition profiles, human exposure, or environmental emissions. In this study, the occurrence of SPAs was evaluated in 15 categories of 214 PCPs collected in Toronto, Canada. Nine SPAs were detected in the PCPs, of which only 2,6-di-tert-butyl-4-methylphenol (BHT, < method quantification limit (MQL)-827 900 ng/g, mean: 35 602 ng/g, median: 249 ng/g) was observed with a detection frequency of >50%. When the 214 PCPs were separated into products labeled as containing BHT and those labeled as not containing BHT, the BHT-labeled PCPs (mean: 369 253 ng//g, median: 382 560 ng/g) contained significantly higher concentrations of BHT than the BHT-unlabeled PCPs (mean: 4960 ng/g, median: 199 ng/g) did (p < 0.01). Five transformation products (TPs) of BHT were also detected in the PCPs at low concentrations (∑TPs: < MQL to 19 014 ng/g, mean: 730 ng/g, median: < MQL) and detection frequencies (12.6-37.4%). Preliminary calculations found that dermal absorption via PCP use may be an important exposure pathway for BHT (mean: 565 879 ng/day median: 2988 ng/day), although this is a negligible exposure pathway for other SPAs. In addition, the estimated discharges of BHT (mean: 7852 g/day, median: 88 g/day) via greywater after PCP use were calculated, which represents a nonignorable source of BHT loading into wastewater treatment plants in Toronto (contributing 10%). To our knowledge, this is the first evaluation of human exposure to and discharge of SPAs via PCP use.

Unexpectedly High Concentrations of a Newly Identified Organophosphate Ester, Tris(2,4-di- tert-butylphenyl) Phosphate, in Indoor Dust from Canada.

Organophosphate esters (OPEs) represent a group of additives with significant levels of production and significant application to various household and industrial products. Given their potential adverse effects on human health, accurate analysis of novel OPEs in indoor dust is crucial. In this study, the novel tris(2,4-di- tert-butylphenyl) phosphate (AO168═O) and six well-known OPEs were investigated. The seven target OPEs were detected in 100% of the office and home dust samples, with ∑OPEs (sum of the OPE concentrations) ranging from 2.92 to 124 µg/g [geometric mean (GM) of 12.3 µg/g]. Surprisingly, the novel AO168═O (0.10-11.1 µg/g, GM of 1.97 µg/g) was among the highest-concentration congeners, contributing 1.36-65.5% to ∑OPEs (mean of 20.7%). AO168═O was the dominant congener in the home dust samples, indicating it is an important OPE congener overlooked previously. AO168═O was also detected in Standard Reference Material 2585 (indoor dust) at an elevated concentration of 10.9 µg/g, which was significantly higher than the concentrations of the other target OPEs (0.38-2.17 µg/g). Despite the high concentrations measured in this study, no industrial production or application could be identified for AO168═O. The precursor of AO168═O, tris(2,4-di- tert-butylphenyl) phosphite, was detected in 50% of the dust samples, with a GM concentration of 1.48 ng/g. This study demonstrates that human OPE exposure in indoor environments is greater than was previously reported. This is the first report of the occurrence of AO168═O, its precursor, and its hydrolysis products in the environment.

First Detection of Photoinitiators and Metabolites in Human Sera from United States Donors.

Photoinitiators (PIs), including benzophenones (BZPs), thioxanthones (TXs), and amine co-initiators (ACIs), are commonly used in photopolymerization systems, and their contamination in foodstuffs and the environment is attracting attention. Although humans are likely exposed to PIs, no data on human burdens of these chemicals are available. In this study, 18 PIs were detected in 50 individual human serum samples with concentrations of ΣPIs (sum of the detected PIs) from 423 to 2870 pg/mL (geometric mean, GM: 836 pg/mL). ΣBZPs (231-1240 ng/g,; GM: 593 pg/mL) were the dominant components, while ΣTXs (21.0-1431 ng/g; GM: 145 pg/mL) and ΣACIs (11.3-976 ng/g; GM: 48.5 pg/mL) were much lower. Data analysis found significantly higher concentrations of most PIs in the male sera than in the female ( p < 0.05). ΣPIs (2921-4139 ng/g; GM: 3621 pg/mL) were also detected in five pooled serum samples, each from at least 1000 donors, indicating the prevalent human burdens of PIs in a large population. Human liver S9 biodegradations of representative PIs, 2-isopropylthioxanthone (2-ITX) and 2,4-diethylthioxanthone (DETX), were conducted. Hydroxylation, sulfoxide, and sulfone metabolites of DETX and 2-ITX were identified by high resolution mass spectrometry in human liver S9 incubation systems. With synthesized standards, the sulfoxide and sulfone metabolites were successfully detected in the human serum samples, which contributed substantially to total human burdens. The ubiquitous presence of PIs in human sera indicates significant human exposure to PIs, although photopolymerization reaction has been generally considered a green technology.

Sorption of Perfluoroalkyl Phosphonates and Perfluoroalkyl Phosphinates in Soils.

Perfluoroalkyl phosphonates (PFPAs) and perfluoroalkyl phosphinates (PFPiAs) are recently discovered perfluoroalkyl acids (PFAAs) that have been widely detected in house dust, aquatic biota, surface water, and wastewater environments. The sorption of C6, C8, and C10 monoalkylated PFPAs and C6/C6, C6/C8, and C8/C8 dialkylated PFPiAs was investigated in seven soils of varying geochemical parameters. Mean distribution coefficients, log Kd*, ranged from 0.2 to 2.1 for the PFPAs and PFPiAs and were generally observed to increase with perfluoroalkyl chain length. The log Kd* of PFPiAs calculated here (1.6-2.1) were similar to those previously measured for the longer-chain perfluorodecanesulfonate (1.9, PFDS) and perfluoroundecanoate (1.7, PFUnA) in sediments, but overall when compared as a class, were greater than those for the perfluoroalkanesulfonates (-0.8-1.9, PFSAs), perfluoroalkyl carboxylates (-0.4-1.7, PFCAs), and PFPAs (0.2-1.5). No single soil-specific parameter, such as pH and organic carbon content, was observed to control the sorption of PFPAs and PFPiAs, the lack of which may be attributed to competing interferences in the naturally heterogeneous soils. The PFPAs were observed to desorb to a greater extent and likely circulate as aqueous contaminants in the environment, while the more sorptive PFPiAs would be preferentially retained by environmental solid phases.

Certain Perfluoroalkyl and Polyfluoroalkyl Substances Associated with Aqueous Film Forming Foam Are Widespread in Canadian Surface Waters.

The presence of perfluoroalkyl and polyfluoroalkyl substances (PFASs) commonly associated with aqueous film forming foams (AFFFs) at sites without known AFFF contamination is a largely unexplored area, which may reveal widespread environmental contaminants requiring further investigation. Sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) screening for 23 classes of PFASs, followed by quantitative analysis was used to investigate surface waters from rural, urban, and AFFF-impacted sites in Canada. The PFASs detected included perfluorohexane sulfonamide (FHxSA), 6:2 fluorotelomer sulfonamide (FTSAm), fluorotelomer sulfonamide alkylbetaines (FTABs), fluorotelomer betaines (FTBs), 6:2 fluorotelomer mercaptoalkylamido sulfonate sulfone (FTSAS-SO2), 6:2 fluorotelomerthiohydroxyl ammonium sulfoxide (FTSHA-SO), 6:2 fluorotelomer sulfonamide alkylamine (FTAA) and C3 to C6 perfluoroalkane sulfonamido amphoterics. Detection of FHxSA in all urban and AFFF-impacted sites (0.04-19 ng/L) indicates the widespread presence of rarely considered perfluorohexanesulfonate (PFHxS) precursors in Canadian waters. FTABs and FTBs were especially abundant with up to 16-33 ng/L of 6:2 FTAB in urban and AFFF-impacted water suggesting it may have additional applications, while FTBs were only in AFFF-impacted sites (qualitative; ∑FTBs 80 ng/L). The distributions of PFASs moving downstream along the AFFF-impacted Welland River and between water and sediment suggested differences in the persistence of various AFFF components and enhanced sorption of long-chain fluorotelomer betaines. Total organofluorine combustion-ion chromatography (TOF-CIC) revealed that fluorotelomer betaines were a substantial portion of the organofluorine in some waters and 36-99.7% of the total organofluorine was not measured in the targeted analysis.

Matrix normalized MALDI-TOF quantification of a fluorotelomer-based acrylate polymer.

The degradation of fluorotelomer-based acrylate polymers (FTACPs) has been hypothesized to serve as a source of the environmental contaminants, perfluoroalkyl carboxylates (PFCAs). Studies have relied on indirect measurement of presumed degradation products to evaluate the environmental fate of FTACPs; however, this approach leaves a degree of uncertainty. The present study describes the development of a quantitative matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry method as the first direct analysis method for FTACPs. The model FTACP used in this study was poly(8:2 FTAC-co-HDA), a copolymer of 8:2 fluorotelomer acrylate (8:2 FTAC) and hexadecyl acrylate (HDA). Instead of relying on an internal standard polymer, the intensities of 40 poly(8:2 FTAC-co-HDA) signals (911-4612 Da) were normalized to the signal intensity of a matrix-sodium cluster (659 Da). We termed this value the normalized polymer response (P(N)). By using the same dithranol solution for the sample preparation of poly(8:2 FTAC-co-HDA) standards, calibration curves with coefficient of determinations (R(2)) typically >0.98 were produced. When poly(8:2 FTAC-co-HDA) samples were prepared with the same dithranol solution as the poly(8:2 FTAC-co-HDA) standards, quantification to within 25% of the theoretical concentration was achieved. This approach minimized the sample-to-sample variability that typically plagues MALDI-TOF, and is the first method developed to directly quantify FTACPs.

Cellular toxicity associated with exposure to perfluorinated carboxylates (PFCAs) and their metabolic precursors.

The biotransformation of fluorotelomer based compounds yields saturated and unsaturated fluorotelomer aldehydes (FTALs and FTUALs, respectively) and carboxylic acids (FTCAs and FTUCAs, respectively) as intermediate metabolites that subsequently transform to perfluorinated carboxylic acids (PFCAs). Previous studies have demonstrated that the FTCAs and FTUCAs are 1 to 5 orders of magnitude more toxic than PFCAs after exposure to aquatic organisms. Additionally, FTUALs have demonstrated reactivity with proteins, which may be associated with toxicity through the inhibition of protein function. The purpose of this study was to carry out a comprehensive assessment of the relative toxicity between PFCAs and their intermediate precursor metabolites: the FTALs, FTUALs, FTCAs, and FTUCAs. Analytes were separately incubated with human liver epithelial (THLE-2) cells to assess how varying the functional group and the fluorinated chain length affects cell viability. For each analyte, dose-response EC50 values were calculated. The EC50 values for FTUCAs and FTCAs were similar, with values ranging from 22 ± 9 and 24 ± 9 µM for the 10:2 congeners to 1004 ± 20 and 1004 ± 24 µM for the 4:2 congeners, respectively. The EC50 values for the PFCAs ranged from 65 ± 41 (PFDA) to 1361 ± 146 (PFBA) µM. The range of toxicity between PFCAs and their acid precursors were similar. However, the comparative toxicity between the 6:2 and 8:2 congeners and their corresponding PFCA had toxicity thresholds that varied depending on the functional headgroup, where FTUALs ≥ FTALs > FTUCAs ≥ FTCAs > PFCAs. For all PFCAs and acid precursors, toxicity depended on the length of the fluorinated chain, where the longer chain lengths yielded greater bioaccumulation and enhanced toxicity, results which agreed with those previously reported. By contrast, FTALs and FTUALs were the most toxic of all the analytes examined, where toxicity was enhanced at shorter chain lengths, with EC50 values of 7 ± 1 µM (6:2 FTUAL) and 8.6 ± 0.8 µM (6:2 FTAL). DNA adducts were not detectable for the aldehyde precursors, using a quantitative long-range PCR method. Our data provide the first evidence that aldehyde intermediates have demonstrated toxicity in cellular systems that is more significant than PFCAs and their corresponding acid intermediates.

Protein binding associated with exposure to fluorotelomer alcohols (FTOHs) and polyfluoroalkyl phosphate esters (PAPs) in rats.

The biotransformation of fluorotelomer-based compounds such as fluorotelomer alcohols (FTOHs) and polyfluoroalkyl phosphate esters (PAPs) are sources of exposure to perfluorinated carboxylates (PFCAs), leading in part to the observation of significant concentrations of PFCAs in human blood. The biotransformation of FTOHs and PAPs yield intermediate metabolites that have been observed to covalently modify proteins. In the current investigation, the extent of covalent protein binding in Sprague-Dawley rats upon exposure to 8:2 FTOH and the 6:2 polyfluoroalkyl phosphate diester (6:2 diPAP) was quantified. The animals were administered a single dose of 8:2 FTOH or 6:2 diPAP at 100 mg/kg by oral gavage to monitor biotransformation and extent of protein binding within the liver, kidney, and plasma. In the 8:2 FTOH-dosed animals, perfluorooctanoate (PFOA) was produced as the primary PFCA, at 623.13 ± 59.3, 459.5 ± 171.8, and 397.3 ± 133.0 ng/g in the plasma, liver, and kidney, respectively. For the animals exposed to 6:2 diPAPs, perfluorohexanoate (PFHxA) was the primary PFCA produced, with maximum concentrations of 57.4 ± 6.5, 9.0 ± 1.2, and 25.3 ± 1.2 ng/g in the plasma, liver, and kidney, respectively. Protein binding was observed in the plasma, liver, and kidney after 8:2 FTOH and 6:2 diPAP exposure, with the most significant binding occurring in the liver (>100 nmol/g protein). This is the first study to link the exposure and in vivo biotransformation of fluorotelomer-based compounds to covalent protein binding.